@article{Joshi:2008, Abstract = {While progenitor-restricted factors broadly specify area identities in developing neocortex, the downstream regulatory elements involved in acquisition of those identities in postmitotic neurons are largely unknown. Here, we identify Bhlhb5, a transcription factor expressed in layers II-V, as a postmitotic regulator of area identity. Bhlhb5 is initially expressed in a high caudomedial to low rostrolateral gradient that transforms into a sharp border between sensory and rostral motor cortices. Bhlhb5 null mice exhibit aberrant expression of area-specific genes and structural organization in the somatosensory and caudal motor cortices. In somatosensory cortex, Bhlhb5 null mice display postsynaptic disorganization of vibrissal barrels. In caudal motor cortex, Bhlhb5 null mice exhibit anomalous differentiation of corticospinal motor neurons, accompanied by failure of corticospinal tract formation. Together, these results demonstrate Bhlhb5's function as an area-specific transcription factor that regulates the postmitotic acquisition of area identities and elucidate the genetic hierarchy between progenitors and postmitotic neurons driving neocortical arealization.}, Author = {Joshi, Pushkar S and Molyneaux, Bradley J and Feng, Liang and Xie, Xiaoling and Macklis, Jeffrey D and Gan, Lin}, Date-Added = {2018-09-18 20:50:58 +0000}, Date-Modified = {2018-09-18 20:50:58 +0000}, Doi = {10.1016/j.neuron.2008.08.006}, Journal = {Neuron}, keywords = {Animals; Basic Helix-Loop-Helix Transcription Factors; Body Patterning; Cell Differentiation; Cell Movement; Efferent Pathways; Mice; Mice, Knockout; Mice, Transgenic; Mitosis; Motor Cortex; Neocortex; Neurons; Pyramidal Tracts; Somatosensory Cortex; Stem Cells; Telencephalon; Transcriptional Activation}, Month = {Oct}, Number = {2}, Pages = {258-72}, Pmc = {PMC2643370}, pmid = {18957218}, Pst = {ppublish}, Title = {Bhlhb5 regulates the postmitotic acquisition of area identities in layers II-V of the developing neocortex}, Volume = {60}, Year = {2008}, url = {papers/Joshi_Neuron2008.pdf}} @article{Strange:2014, Abstract = {The precise functional role of the hippocampus remains a topic of much debate. The dominant view is that the dorsal (or posterior) hippocampus is implicated in memory and spatial navigation and the ventral (or anterior) hippocampus mediates anxiety-related behaviours. However, this 'dichotomy view' may need revision. Gene expression studies demonstrate multiple functional domains along the hippocampal long axis, which often exhibit sharply demarcated borders. By contrast, anatomical studies and electrophysiological recordings in rodents suggest that the long axis is organized along a gradient. Together, these observations suggest a model in which functional long-axis gradients are superimposed on discrete functional domains. This model provides a potential framework to explain and test the multiple functions ascribed to the hippocampus. }, Author = {Strange, Bryan A and Witter, Menno P and Lein, Ed S and Moser, Edvard I}, Date-Added = {2018-07-17 06:25:29 +0000}, Date-Modified = {2018-07-17 06:25:29 +0000}, Doi = {10.1038/nrn3785}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Gene Expression; Hippocampus; Humans}, Month = {Oct}, Number = {10}, Pages = {655-69}, pmid = {25234264}, Pst = {ppublish}, Title = {Functional organization of the hippocampal longitudinal axis}, Volume = {15}, Year = {2014}, url = {papers/Strange_NatRevNeurosci2014.pdf}} @article{Lisman:2017, Author = {Lisman, John and Buzs{\'a}ki, Gy{\"o}rgy and Eichenbaum, Howard and Nadel, Lynn and Ranganath, Charan and Redish, A David}, Date-Added = {2018-07-17 06:24:52 +0000}, Date-Modified = {2018-07-17 06:24:52 +0000}, Doi = {10.1038/nn.4661}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Month = {10}, Number = {11}, Pages = {1434-1447}, Pmc = {PMC5943637}, pmid = {29073641}, Pst = {ppublish}, Title = {Viewpoints: how the hippocampus contributes to memory, navigation and cognition}, Volume = {20}, Year = {2017}, url = {papers/Lisman_NatNeurosci2017.pdf}} @article{Cullen:2017, Abstract = {In this Perspective, we evaluate current progress in understanding how the brain encodes our sense of direction, within the context of parallel work focused on how early vestibular pathways encode self-motion. In particular, we discuss how these systems work together and provide evidence that they involve common mechanisms. We first consider the classic view of the head direction cell and results of recent experiments in rodents and primates indicating that inputs to these neurons encode multimodal information during self-motion, such as proprioceptive and motor efference copy signals, including gaze-related information. We also consider the paradox that, while the head-direction network is generally assumed to generate a fixed representation of perceived directional heading, this computation would need to be dynamically updated when the relationship between voluntary motor command and its sensory consequences changes. Such situations include navigation in virtual reality and head-restricted conditions, since the natural relationship between visual and extravisual cues is altered.}, Author = {Cullen, Kathleen E and Taube, Jeffrey S}, Date-Added = {2018-07-17 06:23:49 +0000}, Date-Modified = {2018-07-17 06:23:49 +0000}, Doi = {10.1038/nn.4658}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Month = {Oct}, Number = {11}, Pages = {1465-1473}, pmid = {29073639}, Pst = {aheadofprint}, Title = {Our sense of direction: progress, controversies and challenges}, Volume = {20}, Year = {2017}, url = {papers/Cullen_NatNeurosci2017.pdf}} @article{Moser:2017, Abstract = {Since the first place cell was recorded and the cognitive-map theory was subsequently formulated, investigation of spatial representation in the hippocampal formation has evolved in stages. Early studies sought to verify the spatial nature of place cell activity and determine its sensory origin. A new epoch started with the discovery of head direction cells and the realization of the importance of angular and linear movement-integration in generating spatial maps. A third epoch began when investigators turned their attention to the entorhinal cortex, which led to the discovery of grid cells and border cells. This review will show how ideas about integration of self-motion cues have shaped our understanding of spatial representation in hippocampal-entorhinal systems from the 1970s until today. It is now possible to investigate how specialized cell types of these systems work together, and spatial mapping may become one of the first cognitive functions to be understood in mechanistic detail.}, Author = {Moser, Edvard I and Moser, May-Britt and McNaughton, Bruce L}, Date-Added = {2018-07-17 06:23:15 +0000}, Date-Modified = {2018-07-17 06:23:15 +0000}, Doi = {10.1038/nn.4653}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Action Potentials; Animals; Brain Mapping; Grid Cells; Hippocampus; Humans; Photic Stimulation; Space Perception}, Month = {Oct}, Number = {11}, Pages = {1448-1464}, pmid = {29073644}, Pst = {ppublish}, Title = {Spatial representation in the hippocampal formation: a history}, Volume = {20}, Year = {2017}, url = {papers/Moser_NatNeurosci2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.4653}} @article{Kim:2014, Abstract = {Larval zebrafish offer the potential for large-scale optical imaging of neural activity throughout the central nervous system; however, several barriers challenge their utility. First, ~panneuronal probe expression has to date only been demonstrated at early larval stages up to 7 days post-fertilization (dpf), precluding imaging at later time points when circuits are more mature. Second, nuclear exclusion of genetically-encoded calcium indicators (GECIs) limits the resolution of functional fluorescence signals collected during imaging. Here, we report the creation of transgenic zebrafish strains exhibiting robust, nuclearly targeted expression of GCaMP3 across the brain up to at least 14 dpf utilizing a previously described optimized Gal4-UAS system. We confirmed both nuclear targeting and functionality of the modified probe in vitro and measured its kinetics in response to action potentials (APs). We then demonstrated in vivo functionality of nuclear-localized GCaMP3 in transgenic zebrafish strains by identifying eye position-sensitive fluorescence fluctuations in caudal hindbrain neurons during spontaneous eye movements. Our methodological approach will facilitate studies of larval zebrafish circuitry by both improving resolution of functional Ca(2+) signals and by allowing brain-wide expression of improved GECIs, or potentially any probe, further into development. }, Author = {Kim, Christina K and Miri, Andrew and Leung, Louis C and Berndt, Andre and Mourrain, Philippe and Tank, David W and Burdine, Rebecca D}, Date-Added = {2018-07-16 22:03:08 +0000}, Date-Modified = {2018-07-16 22:03:08 +0000}, Doi = {10.3389/fncir.2014.00138}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {brain-wide expression; genetically encoded calcium indicators; in vivo calcium imaging; nuclear calcium signals; transgenic zebrafish}, Mesh = {Action Potentials; Animals; Animals, Genetically Modified; Brain; Brain Mapping; Cell Nucleus; Cells, Cultured; Eye Movements; Fluorescence; HEK293 Cells; Humans; Nerve Tissue Proteins; Neural Pathways; Neurons; Nuclear Proteins; Rats; Transfection; Zebrafish; Zebrafish Proteins}, Pages = {138}, Pmc = {PMC4244806}, pmid = {25505384}, Pst = {epublish}, Title = {Prolonged, brain-wide expression of nuclear-localized GCaMP3 for functional circuit mapping}, Volume = {8}, Year = {2014}, url = {papers/Kim_FrontNeuralCircuits2014.pdf}} @article{Bonini:2016, Abstract = {Mirror neurons (MNs) are a fascinating class of cells originally discovered in the ventral premotor cortex (PMv) and, subsequently, in the inferior parietal lobule (IPL) of the macaque, which become active during both the execution and observation of actions. In this review, I will first highlight the mounting evidence indicating that mirroring others' actions engages a broad system of reciprocally connected cortical areas, which extends well beyond the classical IPL-PMv circuit and might even include subcortical regions such as the basal ganglia. Then, I will present the most recent findings supporting the idea that the observation of one's own actions, which might play a role in the ontogenetic origin and tuning of MNs, retains a particular relevance within the adult MN system. Finally, I will propose that both cortical and subcortical mechanisms do exist to decouple MN activity from the motor output, in order to render it exploitable for high-order perceptual, cognitive, and even social functions. The findings reviewed here provide an original framework for envisaging the main challenges and experimental directions of future neurophysiological and neuroanatomical studies of the monkey MN system.}, Author = {Bonini, Luca}, Date-Added = {2018-07-16 22:02:19 +0000}, Date-Modified = {2018-07-16 22:02:19 +0000}, Doi = {10.1177/1073858415626400}, Journal = {Neuroscientist}, Journal-Full = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, Keywords = {action observation; basal ganglia; development; grasping; social cognition}, Month = {Jan}, pmid = {26747293}, Pst = {aheadofprint}, Title = {The Extended Mirror Neuron Network: Anatomy, Origin, and Functions}, Year = {2016}, url = {papers/Bonini_Neuroscientist2016.pdf}} @article{Shadrin:2015, Abstract = {Cardiac cell therapies involving bone marrow-derived human mesenchymal stem cells (hMSCs) have shown promising results, although their mechanisms of action are still poorly understood. Here, we investigated direct interactions between hMSCs and cardiomyocytes in vitro. Using a genetic Ca(2+) indicator gCaMP3 to efficiently label hMSCs in co-cultures with neonatal rat ventricular myocytes (NRVMs), we determined that 25-40% of hMSCs (from 4 independent donors) acquired periodic Ca(2+) transients and cardiac markers through spontaneous fusion with NRVMs. Sharp electrode and voltage-clamp recordings in fused cells showed action potential properties and Ca(2+) current amplitudes in between those of non-fused hMSCs and NRVMs. Time-lapse video-microscopy revealed the first direct evidence of active fusion between hMSCs and NRVMs within several hours of co-culture. Application of blebbistatin, nifedipine or verapamil caused complete and reversible inhibition of fusion, suggesting potential roles for actomyosin bridging and Ca(2+) channels in the fusion process. Immunostaining for Cx43, Ki67, and sarcomeric α-actinin showed that fused cells remain strongly coupled to surrounding NRVMs, but downregulate sarcomeric structures over time, acquiring a non-proliferative and non-contractile phenotype. Overall, these results describe the phenotype and mechanisms of hybrid cell formation via fusion of hMSCs and cardiomyocytes with potential implications for cardiac cell therapy. }, Author = {Shadrin, Ilya Y and Yoon, Woohyun and Li, Liqing and Shepherd, Neal and Bursac, Nenad}, Date-Added = {2018-07-16 22:01:58 +0000}, Date-Modified = {2018-07-16 22:01:58 +0000}, Doi = {10.1038/srep12043}, Journal = {Sci Rep}, Journal-Full = {Scientific reports}, Mesh = {Actinin; Action Potentials; Animals; Caffeine; Calcium; Calcium Channels, L-Type; Cell Fusion; Cell Movement; Cells, Cultured; Coculture Techniques; Connexin 43; Humans; Ions; Mesenchymal Stromal Cells; Microscopy, Video; Myocytes, Cardiac; Myosin Type II; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Time-Lapse Imaging; Troponin T}, Month = {Jul}, Pages = {12043}, Pmc = {PMC4498233}, pmid = {26159124}, Pst = {epublish}, Title = {Rapid fusion between mesenchymal stem cells and cardiomyocytes yields electrically active, non-contractile hybrid cells}, Volume = {5}, Year = {2015}, url = {papers/Shadrin_SciRep2015.pdf}} @article{Cong2017, Abstract = {The internal brain dynamics that link sensation and action are arguably better studied during natural animal behaviors. Here, we report on a novel volume imaging and 3D tracking technique that monitors whole brain neural activity in freely swimming larval zebrafish (\textit{Danio rerio}). We demonstrated the capability of our system through functional imaging of neural activity during visually evoked and prey capture behaviors in larval zebrafish.}, Article_Type = {journal}, Author = {Cong, Lin and Wang, Zeguan and Chai, Yuming and Hang, Wei and Shang, Chunfeng and Yang, Wenbin and Bai, Lu and Du, Jiulin and Wang, Kai and Wen, Quan}, Citation = {eLife 2017;6:e28158}, Date-Added = {2018-07-16 22:01:38 +0000}, Date-Modified = {2018-07-16 22:01:38 +0000}, Doi = {10.7554/eLife.28158}, Editor = {Calabrese, Ronald L}, Issn = {2050-084X}, Journal = {eLife}, Keywords = {freely behaving larval zebrafish, whole brain Imaging, 3D tracking system, light field microscope, prey capture behavior}, Month = {sep}, Pages = {e28158}, Pub_Date = {2017-09-20}, Publisher = {eLife Sciences Publications, Ltd}, Title = {Rapid whole brain imaging of neural activity in freely behaving larval zebrafish (\textit{Danio rerio})}, eprint = {https://doi.org/10.7554/eLife.28158}, Volume = 6, Year = 2017, url = {papers/Cong_eLife2017.pdf}} @article{Itzhaki:2016, Author = {Itzhaki, Ruth F and Lathe, Richard and Balin, Brian J and Ball, Melvyn J and Bearer, Elaine L and Braak, Heiko and Bullido, Maria J and Carter, Chris and Clerici, Mario and Cosby, S Louise and Del Tredici, Kelly and Field, Hugh and Fulop, Tamas and Grassi, Claudio and Griffin, W Sue T and Haas, J{\"u}rgen and Hudson, Alan P and Kamer, Angela R and Kell, Douglas B and Licastro, Federico and Letenneur, Luc and L{\"o}vheim, Hugo and Mancuso, Roberta and Miklossy, Judith and Otth, Carola and Palamara, Anna Teresa and Perry, George and Preston, Christopher and Pretorius, Etheresia and Strandberg, Timo and Tabet, Naji and Taylor-Robinson, Simon D and Whittum-Hudson, Judith A}, Date-Added = {2018-07-16 21:29:57 +0000}, Date-Modified = {2018-07-16 21:29:57 +0000}, Doi = {10.3233/JAD-160152}, Journal = {J Alzheimers Dis}, Journal-Full = {Journal of Alzheimer's disease : JAD}, Mesh = {Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Communicable Diseases; Humans; Microbiota}, Number = {4}, Pages = {979-84}, Pmc = {PMC5457904}, pmid = {26967229}, Pst = {ppublish}, Title = {Microbes and Alzheimer's Disease}, Volume = {51}, Year = {2016}, url = {papers/Itzhaki_JAlzheimersDis2016.pdf}} @article{Barchini2018, Abstract = {Detection of salient objects in the visual scene is a vital aspect of an animal's interactions with its environment. Here, we show that neurons in the mouse superior colliculus (SC) encode visual saliency by detecting motion contrast between stimulus center and surround. Excitatory neurons in the most superficial lamina of the SC are contextually modulated, monotonically increasing their response from suppression by the same-direction surround to maximal potentiation by an oppositely-moving surround. The degree of this potentiation declines with depth in the SC. Inhibitory neurons are suppressed by any surround at all depths. These response modulations in both neuronal populations are much more prominent to direction contrast than to phase, temporal frequency, or static orientation contrast, suggesting feature-specific saliency encoding in the mouse SC. Together, our findings provide evidence supporting locally generated feature representations in the SC, and lay the foundations towards a mechanistic and evolutionary understanding of their emergence.}, Article_Type = {journal}, Author = {Barchini, Jad and Shi, Xuefeng and Chen, Hui and Cang, Jianhua}, Citation = {eLife 2018;7:e35261}, Date-Added = {2018-07-16 21:27:13 +0000}, Date-Modified = {2018-07-16 21:27:13 +0000}, Doi = {10.7554/eLife.35261}, Editor = {Rieke, Fred}, Issn = {2050-084X}, Journal = {eLife}, Month = {jul}, Pages = {e35261}, Pub_Date = {2018-07-02}, Publisher = {eLife Sciences Publications, Ltd}, Title = {Bidirectional encoding of motion contrast in the mouse superior colliculus}, eprint = {https://doi.org/10.7554/eLife.35261}, Volume = 7, Year = 2018, url = {papers/Barchini_eLife2018.pdf}} @article{Tallinen:2016, Author = {Tallinen, Tuomas and Chung, Jun Young and Rousseau, Fran{\c c}ois and Girard, Nadine and Lef{\`e}vre, Julien and Mahadevan, L.}, Date = {2016/02/01/online}, Date-Added = {2018-04-05 23:47:18 +0000}, Date-Modified = {2018-04-05 23:47:18 +0000}, Day = {01}, Journal = {Nature Physics}, L3 = {10.1038/nphys3632; https://www.nature.com/articles/nphys3632#supplementary-information}, Month = {02}, Pages = {588 EP -}, Publisher = {Nature Publishing Group SN -}, Title = {On the growth and form of cortical convolutions}, Ty = {JOUR}, eprint = {http://dx.doi.org/10.1038/nphys3632}, Volume = {12}, Year = {2016}, url = {papers/Tallinen_NaturePhysics2016.pdf}} @article{Tallinen:2014, Abstract = {The exterior of the mammalian brain--the cerebral cortex--has a conserved layered structure whose thickness varies little across species. However, selection pressures over evolutionary time scales have led to cortices that have a large surface area to volume ratio in some organisms, with the result that the brain is strongly convoluted into sulci and gyri. Here we show that the gyrification can arise as a nonlinear consequence of a simple mechanical instability driven by tangential expansion of the gray matter constrained by the white matter. A physical mimic of the process using a layered swelling gel captures the essence of the mechanism, and numerical simulations of the brain treated as a soft solid lead to the formation of cusped sulci and smooth gyri similar to those in the brain. The resulting gyrification patterns are a function of relative cortical expansion and relative thickness (compared with brain size), and are consistent with observations of a wide range of brains, ranging from smooth to highly convoluted. Furthermore, this dependence on two simple geometric parameters that characterize the brain also allows us to qualitatively explain how variations in these parameters lead to anatomical anomalies in such situations as polymicrogyria, pachygyria, and lissencephalia.}, Author = {Tallinen, Tuomas and Chung, Jun Young and Biggins, John S and Mahadevan, L}, Date-Added = {2018-04-05 22:32:15 +0000}, Date-Modified = {2018-04-05 22:32:15 +0000}, Doi = {10.1073/pnas.1406015111}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {brain morphogenesis; elastic instability}, Mesh = {Cell Proliferation; Cerebral Cortex; Compressive Strength; Dimethylpolysiloxanes; Elasticity; Gels; Humans; Models, Anatomic; Models, Neurological; Nerve Fibers, Myelinated; Neural Pathways; Neurons; Stress, Mechanical}, Month = {Sep}, Number = {35}, Pages = {12667-72}, Pmc = {PMC4156754}, pmid = {25136099}, Pst = {ppublish}, Title = {Gyrification from constrained cortical expansion}, Volume = {111}, Year = {2014}, url = {papers/Tallinen_ProcNatlAcadSciUSA2014.pdf}} @article{Treweek:2015, Abstract = {To facilitate fine-scale phenotyping of whole specimens, we describe here a set of tissue fixation-embedding, detergent-clearing and staining protocols that can be used to transform excised organs and whole organisms into optically transparent samples within 1-2 weeks without compromising their cellular architecture or endogenous fluorescence. PACT (passive CLARITY technique) and PARS (perfusion-assisted agent release in situ) use tissue-hydrogel hybrids to stabilize tissue biomolecules during selective lipid extraction, resulting in enhanced clearing efficiency and sample integrity. Furthermore, the macromolecule permeability of PACT- and PARS-processed tissue hybrids supports the diffusion of immunolabels throughout intact tissue, whereas RIMS (refractive index matching solution) grants high-resolution imaging at depth by further reducing light scattering in cleared and uncleared samples alike. These methods are adaptable to difficult-to-image tissues, such as bone (PACT-deCAL), and to magnified single-cell visualization (ePACT). Together, these protocols and solutions enable phenotyping of subcellular components and tracing cellular connectivity in intact biological networks.}, Author = {Treweek, Jennifer B and Chan, Ken Y and Flytzanis, Nicholas C and Yang, Bin and Deverman, Benjamin E and Greenbaum, Alon and Lignell, Antti and Xiao, Cheng and Cai, Long and Ladinsky, Mark S and Bjorkman, Pamela J and Fowlkes, Charless C and Gradinaru, Viviana}, Date-Added = {2018-02-28 22:23:31 +0000}, Date-Modified = {2018-02-28 22:23:31 +0000}, Doi = {10.1038/nprot.2015.122}, Journal = {Nat Protoc}, Journal-Full = {Nature protocols}, Mesh = {Animals; Detergents; Histocytochemistry; Lipids; Mice; Optical Imaging; Pathology; Rats; Specimen Handling; Staining and Labeling; Time Factors; Tissue Embedding; Tissue Fixation}, Month = {Nov}, Number = {11}, Pages = {1860-1896}, Pmc = {PMC4917295}, pmid = {26492141}, Pst = {ppublish}, Title = {Whole-body tissue stabilization and selective extractions via tissue-hydrogel hybrids for high-resolution intact circuit mapping and phenotyping}, Volume = {10}, Year = {2015}, url = {papers/Treweek_NatProtoc2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nprot.2015.122}} @article{Treweek:2016, Abstract = {The scientific community has learned a great deal from imaging small and naturally transparent organisms such as nematodes and zebrafish. The consequences of genetic mutations on their organ development and survival can be visualized easily and with high-throughput at the organism-wide scale. In contrast, three-dimensional information is less accessible in mammalian subjects because the heterogeneity of light-scattering tissue elements renders their organs opaque. Likewise, genetically labeling desired circuits across mammalian bodies is prohibitively slow and costly via the transgenic route. Emerging breakthroughs in viral vector engineering, genome editing tools, and tissue clearing can render larger opaque organisms genetically tractable and transparent for whole-organ cell phenotyping, tract tracing and imaging at depth.}, Author = {Treweek, Jennifer Brooke and Gradinaru, Viviana}, Date-Added = {2018-02-28 22:23:19 +0000}, Date-Modified = {2018-02-28 22:23:19 +0000}, Doi = {10.1016/j.copbio.2016.03.012}, Journal = {Curr Opin Biotechnol}, Journal-Full = {Current opinion in biotechnology}, Mesh = {Animals; Cell Physiological Phenomena; Cell Tracking; Drug Delivery Systems; Genetic Vectors; Humans; Imaging, Three-Dimensional; Phenotype; Single-Cell Analysis; Whole Body Imaging}, Month = {Aug}, Pages = {193-207}, Pmc = {PMC4975678}, pmid = {27393829}, Pst = {ppublish}, Title = {Extracting structural and functional features of widely distributed biological circuits with single cell resolution via tissue clearing and delivery vectors}, Volume = {40}, Year = {2016}, url = {papers/Treweek_CurrOpinBiotechnol2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.copbio.2016.03.012}} @article{Cho:2017, Abstract = {Ventral midbrain dopamine (DA) is unambiguously involved in motivation and behavioral arousal, yet the contributions of other DA populations to these processes are poorly understood. Here, we demonstrate that the dorsal raphe nucleus DA neurons are critical modulators of behavioral arousal and sleep-wake patterning. Using simultaneous fiber photometry and polysomnography, we observed time-delineated dorsal raphe nucleus dopaminergic (DRNDA) activity upon exposure to arousal-evoking salient cues, irrespective of their hedonic valence. We also observed broader fluctuations of DRNDAactivity across sleep-wake cycles with highest activity during wakefulness. Both endogenous DRNDAactivity and optogenetically driven DRNDAactivity were associated with waking from sleep, with DA signal strength predictive of wake duration. Conversely, chemogenetic inhibition opposed wakefulness and promoted NREM sleep, even in the face of salient stimuli. Therefore, the DRNDApopulation is a critical contributor to wake-promoting pathways and is capable of modulating sleep-wake states according to the outside environment, wherein the perception of salient stimuli prompts vigilance and arousal.}, Author = {Cho, Jounhong Ryan and Treweek, Jennifer B and Robinson, J Elliott and Xiao, Cheng and Bremner, Lindsay R and Greenbaum, Alon and Gradinaru, Viviana}, Date-Added = {2018-02-28 22:23:01 +0000}, Date-Modified = {2018-02-28 22:23:01 +0000}, Doi = {10.1016/j.neuron.2017.05.020}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {arousal; chemogenetics; dopamine; dorsal raphe nucleus; fiber photometry; in vivo optical imaging during behavior; optogenetics; salience; sleep-wake state; ventral periaqueductal gray}, Mesh = {Animals; Arousal; Dopaminergic Neurons; Dorsal Raphe Nucleus; Electroencephalography; Electromyography; Hindlimb Suspension; Mice; Optical Imaging; Optogenetics; Photometry; Restraint, Physical; Sleep; Sleep, REM; Wakefulness}, Month = {Jun}, Number = {6}, Pages = {1205-1219.e8}, pmid = {28602690}, Pst = {ppublish}, Title = {Dorsal Raphe Dopamine Neurons Modulate Arousal and Promote Wakefulness by Salient Stimuli}, Volume = {94}, Year = {2017}, url = {papers/Cho_Neuron2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2017.05.020}} @article{Owen:2018, Abstract = {Fast-spiking interneurons (FSIs) are a prominent class of forebrain GABAergic cells implicated in two seemingly independent network functions: gain control and network plasticity. Little is known, however, about how these roles interact. Here, we use a combination of cell-type-specific ablation, optogenetics, electrophysiology, imaging, and behavior to describe a unified mechanism by which striatal FSIs control burst firing, calcium influx, and synaptic plasticity in neighboring medium spiny projection neurons (MSNs). In vivo silencing of FSIs increased bursting, calcium transients, and AMPA/NMDA ratios in MSNs. In a motor sequence task, FSI silencing increased the frequency of calcium transients but reduced the specificity with which transients aligned to individual task events. Consistent with this, ablation of FSIs disrupted the acquisition of striatum-dependent egocentric learning strategies. Together, our data support a model in which feedforward inhibition from FSIs temporally restricts MSN bursting and calcium-dependent synaptic plasticity to facilitate striatum-dependent sequence learning.}, Author = {Owen, Scott F and Berke, Joshua D and Kreitzer, Anatol C}, Date-Added = {2018-02-28 22:20:45 +0000}, Date-Modified = {2018-02-28 22:20:45 +0000}, Doi = {10.1016/j.cell.2018.01.005}, Journal = {Cell}, Journal-Full = {Cell}, Month = {Feb}, Number = {4}, Pages = {683-695.e15}, Pmc = {PMC5810594}, pmid = {29425490}, Pst = {ppublish}, Title = {Fast-Spiking Interneurons Supply Feedforward Control of Bursting, Calcium, and Plasticity for Efficient Learning}, Volume = {172}, Year = {2018}, url = {papers/Owen_Cell2018.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2018.01.005}} @article{Owen:2013, Abstract = {Neuromodulatory control by oxytocin is essential to a wide range of social, parental and stress-related behaviours. Autism spectrum disorders (ASD) are associated with deficiencies in oxytocin levels and with genetic alterations of the oxytocin receptor (OXTR). Thirty years ago, M{\"u}hlethaler et al. found that oxytocin increases the firing of inhibitory hippocampal neurons, but it remains unclear how elevated inhibition could account for the ability of oxytocin to improve information processing in the brain. Here we describe in mammalian hippocampus a simple yet powerful mechanism by which oxytocin enhances cortical information transfer while simultaneously lowering background activity, thus greatly improving the signal-to-noise ratio. Increased fast-spiking interneuron activity not only suppresses spontaneous pyramidal cell firing, but also enhances the fidelity of spike transmission and sharpens spike timing. Use-dependent depression at the fast-spiking interneuron-pyramidal cell synapse is both necessary and sufficient for the enhanced spike throughput. We show the generality of this novel circuit mechanism by activation of fast-spiking interneurons with cholecystokinin or channelrhodopsin-2. This provides insight into how a diffusely delivered neuromodulator can improve the performance of neural circuitry that requires synapse specificity and millisecond precision.}, Author = {Owen, Scott F and Tuncdemir, Sebnem N and Bader, Patrick L and Tirko, Natasha N and Fishell, Gord and Tsien, Richard W}, Date-Added = {2018-02-28 22:19:24 +0000}, Date-Modified = {2018-02-28 22:19:24 +0000}, Doi = {10.1038/nature12330}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Action Potentials; Animals; Brain; Cholecystokinin; Excitatory Postsynaptic Potentials; Feedback, Physiological; Glycine; Hippocampus; Interneurons; Mice; Neural Pathways; Oxytocin; Pyramidal Cells; Rats; Receptors, Oxytocin; Rhodopsin; Synapses; Synaptic Transmission; Threonine}, Month = {Aug}, Number = {7463}, Pages = {458-62}, Pmc = {PMC5283693}, pmid = {23913275}, Pst = {ppublish}, Title = {Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons}, Volume = {500}, Year = {2013}, url = {papers/Owen_Nature2013.pdf}} @article{De-Biase:2017, Abstract = {Microglia play critical roles in tissue homeostasis and can also modulate neuronal function and synaptic connectivity. In contrast to astrocytes and oligodendrocytes, which arise from multiple progenitor pools, microglia arise from yolk sac progenitors and are widely considered to be equivalent throughout the CNS. However, little is known about basic properties of deep brain microglia, such as those within the basal ganglia (BG). Here, we show that microglial anatomical features, lysosome content, membrane properties, and transcriptomes differ significantly across BG nuclei. Region-specific phenotypes of BG microglia emerged during the second postnatal week and were re-established following genetic or pharmacological microglial ablation and repopulation in the adult, indicating that local cues play an ongoing role in shaping microglial diversity. These findings demonstrate that microglia in the healthy brain exhibit a spectrum of distinct functional states and provide a critical foundation for defining microglial contributions to BG circuit function.}, Author = {De Biase, Lindsay M and Schuebel, Kornel E and Fusfeld, Zachary H and Jair, Kamwing and Hawes, Isobel A and Cimbro, Raffaello and Zhang, Hai-Ying and Liu, Qing-Rong and Shen, Hui and Xi, Zheng-Xiong and Goldman, David and Bonci, Antonello}, Date-Added = {2018-02-28 22:15:11 +0000}, Date-Modified = {2018-02-28 22:15:11 +0000}, Doi = {10.1016/j.neuron.2017.06.020}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {RNA sequencing; density; development; electrophysiology; heterogeneity; microglia; morphology; nucleus accumbens; substantia nigra; ventral tegmental area}, Mesh = {Animals; Basal Ganglia; Cues; Mice, Transgenic; Microglia; Neurons; Phenotype}, Month = {Jul}, Number = {2}, Pages = {341-356.e6}, Pmc = {PMC5754189}, pmid = {28689984}, Pst = {ppublish}, Title = {Local Cues Establish and Maintain Region-Specific Phenotypes of Basal Ganglia Microglia}, Volume = {95}, Year = {2017}, url = {papers/DeBiase_Neuron2017.pdf}, Bdsk-File-2 = {papers/DeBiase_Neuron2017a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2017.06.020}} @article{Sylwestrak:2016, Abstract = {In recently developed approaches for high-resolution imaging within intact tissue, molecular characterization over large volumes has been largely restricted to labeling of proteins. But volumetric nucleic acid labeling may represent a far greater scientific and clinical opportunity, enabling detection of not only diverse coding RNA variants but also non-coding RNAs. Moreover, scaling immunohistochemical detection to large tissue volumes has limitations due to high cost, limited renewability/availability, and restricted multiplexing capability of antibody labels. With the goal of versatile, high-content, and scalable molecular phenotyping of intact tissues, we developed a method using carbodiimide-based chemistry to stably retain RNAs in clarified tissue, coupled with amplification tools for multiplexed detection. The resulting technology enables robust measurement of activity-dependent transcriptional signatures, cell-identity markers, and diverse non-coding RNAs in rodent and human tissue volumes. The growing set of validated probes is deposited in an online resource for nucleating related developments from across the scientific community.}, Author = {Sylwestrak, Emily Lauren and Rajasethupathy, Priyamvada and Wright, Matthew Arnot and Jaffe, Anna and Deisseroth, Karl}, Date-Added = {2018-02-28 22:14:13 +0000}, Date-Modified = {2018-02-28 22:14:13 +0000}, Doi = {10.1016/j.cell.2016.01.038}, Journal = {Cell}, Journal-Full = {Cell}, Mesh = {Adolescent; Animals; Brain Chemistry; Cyanates; Ethyldimethylaminopropyl Carbodiimide; Female; Humans; In Situ Hybridization; Male; Maleimides; Mice; Middle Aged; Nucleic Acid Amplification Techniques; Oligonucleotides; RNA; Succinimides; Transcriptome}, Month = {Feb}, Number = {4}, Pages = {792-804}, Pmc = {PMC4775740}, pmid = {26871636}, Pst = {ppublish}, Title = {Multiplexed Intact-Tissue Transcriptional Analysis at Cellular Resolution}, Volume = {164}, Year = {2016}, url = {papers/Sylwestrak_Cell2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2016.01.038}} @article{Li:2009, Abstract = {Type 1 cannabinoid (CB1) receptors mediate widespread synaptic plasticity, but how this contributes to systems-level plasticity and development in vivo is unclear. We tested whether CB1 signaling is required for development and plasticity of the whisker map in rat somatosensory cortex. Treatment with the CB1 antagonist AM251 during an early critical period for layer (L) 2/3 development (beginning postnatal day [P] 12-16) disrupted whisker map development, leading to inappropriate whisker tuning in L2/3 column edges and a blurred map. Early AM251 treatment also prevented experience-dependent plasticity in L2/3, including deprivation-induced synapse weakening and weakening of deprived whisker responses. CB1 blockade after P25 did not disrupt map development or plasticity. AM251 had no acute effect on sensory-evoked spiking and only modestly affected field potentials, suggesting that plasticity effects were not secondary to gross activity changes. These findings implicate CB1-dependent plasticity in systems-level development and early postnatal plasticity of the whisker map.}, Author = {Li, Lu and Bender, Kevin J and Drew, Patrick J and Jadhav, Shantanu P and Sylwestrak, Emily and Feldman, Daniel E}, Date-Added = {2018-02-28 22:12:59 +0000}, Date-Modified = {2018-02-28 22:12:59 +0000}, Doi = {10.1016/j.neuron.2009.10.005}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Critical Period (Psychology); Female; Male; Mice; Mice, Knockout; Neuronal Plasticity; Rats; Rats, Long-Evans; Receptor, Cannabinoid, CB1; Signal Transduction; Somatosensory Cortex; Vibrissae}, Month = {Nov}, Number = {4}, Pages = {537-49}, Pmc = {PMC2796273}, pmid = {19945395}, Pst = {ppublish}, Title = {Endocannabinoid signaling is required for development and critical period plasticity of the whisker map in somatosensory cortex}, Volume = {64}, Year = {2009}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.10.005}} @article{Kim:2015, Abstract = {Cortical layer 5 (L5) pyramidal neurons integrate inputs from many sources and distribute outputs to cortical and subcortical structures. Previous studies demonstrate two L5 pyramid types: cortico-cortical (CC) and cortico-subcortical (CS). We characterize connectivity and function of these cell types in mouse primary visual cortex and reveal a new subtype. Unlike previously described L5 CC and CS neurons, this new subtype does not project to striatum [cortico-cortical, non-striatal (CC-NS)] and has distinct morphology, physiology, and visual responses. Monosynaptic rabies tracing reveals that CC neurons preferentially receive input from higher visual areas, while CS neurons receive more input from structures implicated in top-down modulation of brain states. CS neurons are also more direction-selective and prefer faster stimuli than CC neurons. These differences suggest distinct roles as specialized output channels, with CS neurons integrating information and generating responses more relevant to movement control and CC neurons being more important in visual perception.}, Author = {Kim, Euiseok J and Juavinett, Ashley L and Kyubwa, Espoir M and Jacobs, Matthew W and Callaway, Edward M}, Date-Added = {2018-02-28 22:11:15 +0000}, Date-Modified = {2018-02-28 22:11:15 +0000}, Doi = {10.1016/j.neuron.2015.11.002}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Neurons; Pyramidal Cells; Visual Cortex}, Month = {Dec}, Number = {6}, Pages = {1253-67}, Pmc = {PMC4688126}, pmid = {26671462}, Pst = {ppublish}, Title = {Three Types of Cortical Layer 5 Neurons That Differ in Brain-wide Connectivity and Function}, Volume = {88}, Year = {2015}, url = {papers/Kim_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.11.002}} @article{Sylwestrak:2012, Abstract = {Although synaptic transmission may be unidirectional, the establishment of synaptic connections with specific properties can involve bidirectional signaling. Pyramidal neurons in the hippocampus form functionally distinct synapses onto two types of interneurons. Excitatory synapses onto oriens-lacunosum moleculare (O-LM) interneurons are facilitating and have a low release probability, whereas synapses onto parvalbumin interneurons are depressing and have a high release probability. Here, we show that the extracellular leucine-rich repeat fibronectin containing 1 (Elfn1) protein is selectively expressed by O-LM interneurons and regulates presynaptic release probability to direct the formation of highly facilitating pyramidal-O-LM synapses. Thus, postsynaptic expression of Elfn1 in O-LM interneurons regulates presynaptic release probability, which confers target-specific synaptic properties to pyramidal cell axons.}, Author = {Sylwestrak, Emily L and Ghosh, Anirvan}, Date-Added = {2018-02-28 22:10:31 +0000}, Date-Modified = {2018-02-28 22:10:31 +0000}, Doi = {10.1126/science.1222482}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Animals; Axons; CA1 Region, Hippocampal; Cells, Cultured; Gene Knockdown Techniques; Green Fluorescent Proteins; HEK293 Cells; Humans; Interneurons; Mice; Nerve Tissue Proteins; RNA, Small Interfering; Rats; Rats, Inbred LEC; Synapses; Synaptic Transmission}, Month = {Oct}, Number = {6106}, Pages = {536-40}, Pmc = {PMC5297939}, pmid = {23042292}, Pst = {ppublish}, Title = {Elfn1 regulates target-specific release probability at CA1-interneuron synapses}, Volume = {338}, Year = {2012}, url = {papers/Sylwestrak_Science2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1222482}} @article{Beier:2017, Abstract = {Identification of neural circuit changes that contribute to behavioural plasticity has routinely been conducted on candidate circuits that were preselected on the basis of previous results. Here we present an unbiased method for identifying experience-triggered circuit-level changes in neuronal ensembles in mice. Using rabies virus monosynaptic tracing, we mapped cocaine-induced global changes in inputs onto neurons in the ventral tegmental area. Cocaine increased rabies-labelled inputs from the globus pallidus externus (GPe), a basal ganglia nucleus not previously known to participate in behavioural plasticity triggered by drugs of abuse. We demonstrated that cocaine increased GPe neuron activity, which accounted for the increase in GPe labelling. Inhibition of GPe activity revealed that it contributes to two forms of cocaine-triggered behavioural plasticity, at least in part by disinhibiting dopamine neurons in the ventral tegmental area. These results suggest that rabies-based unbiased screening of changes in input populations can identify previously unappreciated circuit elements that critically support behavioural adaptations.}, Author = {Beier, Kevin T and Kim, Christina K and Hoerbelt, Paul and Hung, Lin Wai and Heifets, Boris D and DeLoach, Katherine E and Mosca, Timothy J and Neuner, Sophie and Deisseroth, Karl and Luo, Liqun and Malenka, Robert C}, Date-Added = {2018-02-28 22:08:40 +0000}, Date-Modified = {2018-02-28 22:08:40 +0000}, Doi = {10.1038/nature23888}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Basal Ganglia; Cocaine; Dopaminergic Neurons; Female; Globus Pallidus; Male; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Rabies virus; Staining and Labeling; Ventral Tegmental Area}, Month = {09}, Number = {7672}, Pages = {345-350}, pmid = {28902833}, Pst = {ppublish}, Title = {Rabies screen reveals GPe control of cocaine-triggered plasticity}, Volume = {549}, Year = {2017}, url = {papers/Beier_Nature2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature23888}} @article{De-Biase:2010, Abstract = {The mammalian CNS contains an abundant, widely distributed population of glial cells that serve as oligodendrocyte progenitors. It has been reported that these NG2-immunoreactive cells (NG2(+) cells) form synapses and generate action potentials, suggesting that neural-evoked excitation of these progenitors may regulate oligodendrogenesis. However, recent studies also suggest that NG2(+) cells are comprised of functionally distinct groups that differ in their ability to respond to neuronal activity, undergo differentiation, and experience injury following ischemia. To better define the physiological properties of NG2(+) cells, we used transgenic mice that allowed an unbiased sampling of this population and unambiguous identification of cells in discrete states of differentiation. Using acute brain slices prepared from developing and mature mice, we found that NG2(+) cells in diverse brain regions share a core set of physiological properties, including expression of voltage-gated Na(+) (NaV) channels and ionotropic glutamate receptors, and formation of synapses with glutamatergic neurons. Although small amplitude Na(+) spikes could be elicited in some NG2(+) cells during the first postnatal week, they were not capable of generating action potentials. Transition of these progenitors to the premyelinating stage was accompanied by the rapid removal of synaptic input, as well as downregulation of AMPA and NMDA receptors and NaV channels. Thus, prior reports of physiological heterogeneity among NG2(+) cells may reflect analysis of cells in later stages of maturation. These results suggest that NG2(+) cells are uniquely positioned within the oligodendrocyte lineage to monitor the firing patterns of surrounding neurons.}, Author = {De Biase, Lindsay M and Nishiyama, Akiko and Bergles, Dwight E}, Date-Added = {2018-02-28 22:03:44 +0000}, Date-Modified = {2018-02-28 22:03:44 +0000}, Doi = {10.1523/JNEUROSCI.6000-09.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Action Potentials; Animals; Animals, Newborn; Cell Communication; Cell Lineage; Chondroitin Sulfate Proteoglycans; Gene Expression Profiling; Membrane Proteins; Mice; Mice, Transgenic; Oligodendroglia; Synapses}, Month = {Mar}, Number = {10}, Pages = {3600-11}, Pmc = {PMC2838193}, pmid = {20219994}, Pst = {ppublish}, Title = {Excitability and synaptic communication within the oligodendrocyte lineage}, Volume = {30}, Year = {2010}, url = {papers/DeBiase_JNeurosci2010.pdf}} @article{Beier:2013, Abstract = {The use of neurotropic viruses as transsynaptic tracers was first described in the 1960s, but only recently have such viruses gained popularity as a method for labeling neural circuits. The development of retrograde monosynaptic tracing vectors has enabled visualization of the presynaptic sources onto defined sets of postsynaptic neurons. Here, we describe the first application of a novel viral tracer, based on vesicular stomatitis virus (VSV), which directs retrograde transsynaptic viral spread between defined cell types. We use this virus in the mouse retina to show connectivity between starburst amacrine cells (SACs) and their known synaptic partners, direction-selective retinal ganglion cells, as well as to discover previously unknown connectivity between SACs and other retinal ganglion cell types. These novel connections were confirmed using physiological recordings. VSV transsynaptic tracing enables cell type-specific dissection of neural circuitry and can reveal synaptic relationships among neurons that are otherwise obscured due to the complexity and density of neuropil.}, Author = {Beier, Kevin T and Borghuis, Bart G and El-Danaf, Rana N and Huberman, Andrew D and Demb, Jonathan B and Cepko, Constance L}, Date-Added = {2018-02-28 22:03:01 +0000}, Date-Modified = {2018-02-28 22:03:01 +0000}, Doi = {10.1523/JNEUROSCI.0245-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Mice; Nerve Net; Neuronal Tract-Tracers; Neurons; Retina; Synapses; Vesiculovirus}, Month = {Jan}, Number = {1}, Pages = {35-51}, Pmc = {PMC3711516}, pmid = {23283320}, Pst = {ppublish}, Title = {Transsynaptic tracing with vesicular stomatitis virus reveals novel retinal circuitry}, Volume = {33}, Year = {2013}, url = {papers/Beier_JNeurosci2013.pdf}} @article{Sher:2013, Abstract = {CNS neurons change their connectivity to accommodate a changing environment, form memories, or respond to injury. Plasticity in the adult mammalian retina after injury or disease was thought to be limited to restructuring resulting in abnormal retinal anatomy and function. Here we report that neurons in the mammalian retina change their connectivity and restore normal retinal anatomy and function after injury. Patches of photoreceptors in the rabbit retina were destroyed by selective laser photocoagulation, leaving retinal inner neurons (bipolar, amacrine, horizontal, ganglion cells) intact. Photoreceptors located outside of the damaged zone migrated to make new functional connections with deafferented bipolar cells located inside the lesion. The new connections restored ON and OFF responses in deafferented ganglion cells. This finding extends the previously perceived limits of restorative plasticity in the adult retina and allows for new approaches to retinal laser therapy free of current detrimental side effects such as scotomata and scarring.}, Author = {Sher, Alexander and Jones, Bryan W and Huie, Philip and Paulus, Yannis M and Lavinsky, Daniel and Leung, Loh-Shan S and Nomoto, Hiroyuki and Beier, Corinne and Marc, Robert E and Palanker, Daniel}, Date-Added = {2018-02-28 22:02:52 +0000}, Date-Modified = {2018-02-28 22:02:52 +0000}, Doi = {10.1523/JNEUROSCI.1044-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Disease Models, Animal; Electric Stimulation; Glutamic Acid; In Vitro Techniques; Lasers; Light Coagulation; Male; Patch-Clamp Techniques; Photic Stimulation; Photoreceptor Cells; Rabbits; Recovery of Function; Retina; Retinal Diseases; Retinal Ganglion Cells; Synapses; Time Factors; Tomography, X-Ray Computed; Vision, Ocular; Visual Pathways; gamma-Aminobutyric Acid}, Month = {Apr}, Number = {16}, Pages = {6800-8}, Pmc = {PMC3865506}, pmid = {23595739}, Pst = {ppublish}, Title = {Restoration of retinal structure and function after selective photocoagulation}, Volume = {33}, Year = {2013}, url = {papers/Sher_JNeurosci2013.pdf}} @article{Behrens:2014, Abstract = {Bitter taste perception in vertebrates relies on a variable number of bitter taste receptor (Tas2r) genes, ranging from only three functional genes in chicken to as many as approximately 50 in frogs. Humans possess a medium-sized Tas2r repertoire encoding three broadly and several narrowly tuned receptors plus receptors with intermediate tuning properties. Such tuning information is not available for bitter taste receptors of other vertebrate species. In particular it is not known, whether a small Tas2r repertoire may be compensated for by broad tuning of these receptors, and on the other side, whether a large repertoire might entail a preponderance of narrowly tuned receptors. To elucidate this question, we cloned all three chicken Tas2rs, the two turkey Tas2rs, three zebra finch Tas2rs, and six Tas2rs of the Western clawed frog representative of major branches of the phylogenetic tree, and screened them with 46 different bitter compounds. All chicken and turkey Tas2rs were broadly tuned, the zebra finch Tas2rs were narrowly tuned, and frog Tas2rs ranged from broadly to narrowly tuned receptors. We conclude that a low number of functional Tas2r genes does not imply a reduced importance of bitter taste per se, as it can be compensated by large tuning width. A high number of functional Tas2r genes appears to allow the evolution of specialized receptors, possibly for toxins with species-specific relevance. In sum, we show that variability in tuning breadth, overlapping agonist profiles, and staggered effective agonist concentration ranges are shared features of human and other vertebrate Tas2rs.}, Author = {Behrens, Maik and Korsching, Sigrun I and Meyerhof, Wolfgang}, Date-Added = {2018-02-26 23:45:41 +0000}, Date-Modified = {2018-02-26 23:45:41 +0000}, Doi = {10.1093/molbev/msu254}, Journal = {Mol Biol Evol}, Journal-Full = {Molecular biology and evolution}, Keywords = {G protein-coupled receptor; bitter taste receptor; evolution; heterologous expression}, Mesh = {Amphibian Proteins; Animals; Anura; Avian Proteins; Birds; Evolution, Molecular; HEK293 Cells; Humans; Noscapine; Phylogeny; Quaternary Ammonium Compounds; Receptors, Cell Surface; Signal Transduction; Taste Buds}, Month = {Dec}, Number = {12}, Pages = {3216-27}, pmid = {25180257}, Pst = {ppublish}, Title = {Tuning properties of avian and frog bitter taste receptors dynamically fit gene repertoire sizes}, Volume = {31}, Year = {2014}, url = {papers/Behrens_MolBiolEvol2014.pdf}} @article{Oike:2007, Abstract = {Recent progress in the molecular biology of taste reception has revealed that in mammals, the heteromeric receptors T1R1/3 and T1R2/3 respond to amino acids and sweeteners, respectively, whereas T2Rs are receptors for bitter tastants. Similar taste receptors have also been characterized in fish, but their ligands have not been identified yet. In the present study, we conducted a series of experiments to identify the fish taste receptor ligands. Facial nerve recordings in zebrafish (Danio rerio) demonstrated that the fish perceived amino acids and even denatonium, which is a representative of aversive bitter compounds for mammals and Drosophila. Calcium imaging analysis of T1Rs in zebrafish and medaka fish (Oryzias latipes) using an HEK293T heterologous expression system revealed that both T1R1/3 and a series of T1R2/3 responded to amino acids but not to sugars. A triple-labeling, in situ hybridization analysis demonstrated that cells expressing T1R1/3 and T1R2/3s exist in PLCbeta2-expressing taste bud cells of medaka fish. Functional analysis using T2Rs showed that zfT2R5 and mfT2R1 responded to denatonium. Behavior observations confirmed that zebrafish prefer amino acids and avoid denatonium. These results suggest that, although there may be some fish-specific way of discriminating ligands, vertebrates could have a conserved gustatory mechanism by which T1Rs and T2Rs respond to attractive and aversive tastants, respectively.}, Author = {Oike, Hideaki and Nagai, Toshitada and Furuyama, Akira and Okada, Shinji and Aihara, Yoshiko and Ishimaru, Yoshiro and Marui, Takayuki and Matsumoto, Ichiro and Misaka, Takumi and Abe, Keiko}, Date-Added = {2018-02-26 23:27:48 +0000}, Date-Modified = {2018-02-26 23:27:48 +0000}, Doi = {10.1523/JNEUROSCI.0651-07.2007}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Amino Acids; Animals; Cell Line; Dose-Response Relationship, Drug; Humans; Ligands; Oryzias; Quaternary Ammonium Compounds; Receptors, G-Protein-Coupled; Taste Buds; Zebrafish}, Month = {May}, Number = {21}, Pages = {5584-92}, pmid = {17522303}, Pst = {ppublish}, Title = {Characterization of ligands for fish taste receptors}, Volume = {27}, Year = {2007}, url = {papers/Oike_JNeurosci2007.pdf}} @article{Yu:2016, Abstract = {We rely on movement to explore the environment, for example, by palpating an object. In somatosensory cortex, activity related to movement of digits or whiskers is suppressed, which could facilitate detection of touch. Movement-related suppression is generally assumed to involve corollary discharges. Here we uncovered a thalamocortical mechanism in which cortical fast-spiking interneurons, driven by sensory input, suppress movement-related activity in layer 4 (L4) excitatory neurons. In mice locating objects with their whiskers, neurons in the ventral posteromedial nucleus (VPM) fired in response to touch and whisker movement. Cortical L4 fast-spiking interneurons inherited these responses from VPM. In contrast, L4 excitatory neurons responded mainly to touch. Optogenetic experiments revealed that fast-spiking interneurons reduced movement-related spiking in excitatory neurons, enhancing selectivity for touch-related information during active tactile sensation. These observations suggest a fundamental computation performed by the thalamocortical circuit to accentuate salient tactile information.}, Author = {Yu, Jianing and Gutnisky, Diego A and Hires, S Andrew and Svoboda, Karel}, Date-Added = {2018-02-21 22:24:12 +0000}, Date-Modified = {2018-02-21 22:24:12 +0000}, Doi = {10.1038/nn.4412}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Action Potentials; Animals; Behavior, Animal; Electric Stimulation; Interneurons; Mice; Movement; Neural Pathways; Patch-Clamp Techniques; Physical Stimulation; Somatosensory Cortex; Thalamus; Touch; Vibrissae}, Month = {Dec}, Number = {12}, Pages = {1647-1657}, pmid = {27749825}, Pst = {ppublish}, Title = {Layer 4 fast-spiking interneurons filter thalamocortical signals during active somatosensation}, Volume = {19}, Year = {2016}, url = {papers/Yu_NatNeurosci2016.pdf}} @article{Hartwick:2007, Abstract = {A small number (<2%) of mammalian retinal ganglion cells express the photopigment melanopsin and are intrinsically photosensitive (ipRGCs). Light depolarizes ipRGCs and increases intracellular calcium levels ([Ca2+]i) but the signaling cascades underlying these responses have yet to be elucidated. To facilitate physiological studies on these rare photoreceptors, highly enriched ipRGC cultures from neonatal rats were generated using anti-melanopsin-mediated plate adhesion (immunopanning). This novel approach enabled experiments on isolated ipRGCs, eliminating the potential confounding influence of rod/cone-driven input. Light induced a rise in [Ca2+]i (monitored using fura-2 imaging) in the immunopanned ipRGCs and the source of this Ca2+ signal was investigated. The Ca2+ responses were inhibited by 2-aminoethoxydiphenyl borate, SKF-96365 (1-2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl)propoxy]ethyl-1H-imidazole), flufenamic acid, lanthanum, and gadolinium, consistent with the involvement of canonical transient receptor potential (TRP) channels in ipRGC phototransduction. However, the contribution of direct Ca2+ flux through a putative TRP channel to ipRGC [Ca2+]i was relatively small, as most (approximately 90%) of the light-induced Ca2+ responses could be blocked by preventing action potential firing with tetrodotoxin. The L-type voltage-gated Ca2+ channel (VGCC) blockers verapamil and (+)-cis-diltiazem significantly reduced the light-evoked Ca2+ responses, while the internal Ca2+ stores depleting agent thapsigargin had negligible effect. These results indicate that Ca2+ influx through VGCCs, activated after action potential firing, was the primary source for light-evoked elevations in ipRGC [Ca2+]i. Furthermore, concurrent Ca2+ imaging and cell-attached electrophysiological recordings demonstrated that the Ca2+ responses were highly correlated to spike frequency, thereby establishing a direct link between action potential firing and somatic [Ca2+]i in light-stimulated ipRGCs.}, Author = {Hartwick, Andrew T E and Bramley, Jayne R and Yu, Jianing and Stevens, Kelly T and Allen, Charles N and Baldridge, William H and Sollars, Patricia J and Pickard, Gary E}, Date-Added = {2018-02-21 21:54:31 +0000}, Date-Modified = {2018-02-21 21:54:31 +0000}, Doi = {10.1523/JNEUROSCI.3626-07.2007}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Action Potentials; Animals; Animals, Newborn; Calcium Signaling; Photic Stimulation; Rats; Rats, Long-Evans; Retinal Ganglion Cells; Rod Opsins}, Month = {Dec}, Number = {49}, Pages = {13468-80}, pmid = {18057205}, Pst = {ppublish}, Title = {Light-evoked calcium responses of isolated melanopsin-expressing retinal ganglion cells}, Volume = {27}, Year = {2007}, url = {papers/Hartwick_JNeurosci2007.pdf}} @article{Goyal:2014, Abstract = {Aerobic glycolysis (AG; i.e., nonoxidative metabolism of glucose despite the presence of abundant oxygen) accounts for 10%-12% of glucose used by the adult human brain. AG varies regionally in the resting state. Brain AG may support synaptic growth and remodeling; however, data supporting this hypothesis are sparse. Here, we report on investigations on the role of AG in the human brain. Meta-analysis of prior brain glucose and oxygen metabolism studies demonstrates that AG increases during childhood, precisely when synaptic growth rates are highest. In resting adult humans, AG correlates with the persistence of gene expression typical of infancy (transcriptional neoteny). In brain regions with the highest AG, we find increased gene expression related to synapse formation and growth. In contrast, regions high in oxidative glucose metabolism express genes related to mitochondria and synaptic transmission. Our results suggest that brain AG supports developmental processes, particularly those required for synapse formation and growth.}, Author = {Goyal, Manu S and Hawrylycz, Michael and Miller, Jeremy A and Snyder, Abraham Z and Raichle, Marcus E}, Date-Added = {2018-02-14 00:26:30 +0000}, Date-Modified = {2018-02-14 00:26:36 +0000}, Doi = {10.1016/j.cmet.2013.11.020}, Journal = {Cell Metab}, Journal-Full = {Cell metabolism}, Keywords = {Energy Metabolism}, Mesh = {Adult; Aerobiosis; Brain; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gene Ontology; Glucose; Glycolysis; Humans; Oxygen Consumption; Synapses; Transcription, Genetic}, Month = {Jan}, Number = {1}, Pages = {49-57}, Pmc = {PMC4389678}, pmid = {24411938}, Pst = {ppublish}, Title = {Aerobic glycolysis in the human brain is associated with development and neotenous gene expression}, Volume = {19}, Year = {2014}, url = {papers/Goyal_CellMetab2014.pdf}, Bdsk-File-2 = {papers/Goyal_CellMetab2014a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cmet.2013.11.020}} @article{Magistretti:2015, Abstract = {The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales.}, Author = {Magistretti, Pierre J and Allaman, Igor}, Date-Added = {2018-02-14 00:25:38 +0000}, Date-Modified = {2018-02-14 00:25:45 +0000}, Doi = {10.1016/j.neuron.2015.03.035}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Energy Metabolism}, Mesh = {Animals; Astrocytes; Brain; Energy Metabolism; Glucose; Humans; Magnetic Resonance Imaging; Neurons}, Month = {May}, Number = {4}, Pages = {883-901}, pmid = {25996133}, Pst = {ppublish}, Title = {A cellular perspective on brain energy metabolism and functional imaging}, Volume = {86}, Year = {2015}, url = {papers/Magistretti_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.03.035}} @article{Erecinska:2004, Abstract = {Production of energy for the maintenance of ionic disequilibria necessary for generation and transmission of nerve impulses is one of the primary functions of the brain. This review attempts to link the plethora of information on the maturation of the central nervous system with the ontogeny of ATP metabolism, placing special emphasis on variations that occur during development in different brain regions and across the mammalian species. It correlates morphological events and markers with biochemical changes in activities of enzymes and pathways that participate in the production of ATP. The paper also evaluates alterations in energy levels as a function of age and, based on the tenet that ATP synthesis and utilization cannot be considered in isolation, investigates maturational profiles of the key processes that utilize energy. Finally, an attempt is made to assess the relevance of currently available animal models to improvement of our understanding of the etiopathology of various disease states in the human infant. This is deemed essential for the development and testing of novel strategies for prevention and treatment of several severe neurological deficits.}, Author = {Erecinska, Maria and Cherian, Shobha and Silver, Ian A}, Date-Added = {2018-02-14 00:24:25 +0000}, Date-Modified = {2018-02-14 00:24:46 +0000}, Doi = {10.1016/j.pneurobio.2004.06.003}, Journal = {Prog Neurobiol}, Journal-Full = {Progress in neurobiology}, Keywords = {Energy Metabolism}, Mesh = {Adenosine Triphosphate; Animals; Blood Vessels; Body Water; Brain; Brain Chemistry; Cholesterol; DNA; Energy Metabolism; Extracellular Space; Humans; Ion Channels; Kinetics; Mitochondria; Nerve Tissue Proteins; Neurons}, Month = {Aug}, Number = {6}, Pages = {397-445}, pmid = {15313334}, Pst = {ppublish}, Title = {Energy metabolism in mammalian brain during development}, Volume = {73}, Year = {2004}, url = {papers/Erecinska_ProgNeurobiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.pneurobio.2004.06.003}} @article{Lee:2017, Abstract = {In mammals, taste buds typically contain 50-100 tightly packed taste-receptor cells (TRCs), representing all five basic qualities: sweet, sour, bitter, salty and umami. Notably, mature taste cells have life spans of only 5-20 days and, consequently, are constantly replenished by differentiation of taste stem cells. Given the importance of establishing and maintaining appropriate connectivity between TRCs and their partner ganglion neurons (that is, ensuring that a labelled line from sweet TRCs connects to sweet neurons, bitter TRCs to bitter neurons, sour to sour, and so on), we examined how new connections are specified to retain fidelity of signal transmission. Here we show that bitter and sweet TRCs provide instructive signals to bitter and sweet target neurons via different guidance molecules (SEMA3A and SEMA7A). We demonstrate that targeted expression of SEMA3A or SEMA7A in different classes of TRCs produces peripheral taste systems with miswired sweet or bitter cells. Indeed, we engineered mice with bitter neurons that now responded to sweet tastants, sweet neurons that responded to bitter or sweet neurons responding to sour stimuli. Together, these results uncover the basic logic of the wiring of the taste system at the periphery, and illustrate how a labelled-line sensory circuit preserves signalling integrity despite rapid and stochastic turnover of receptor cells.}, Author = {Lee, Hojoon and Macpherson, Lindsey J and Parada, Camilo A and Zuker, Charles S and Ryba, Nicholas J P}, Date-Added = {2018-02-13 23:59:58 +0000}, Date-Modified = {2018-02-13 23:59:58 +0000}, Doi = {10.1038/nature23299}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Antigens, CD; Ganglia; Mice; Neurons; Semaphorin-3A; Semaphorins; Stem Cells; Sweetening Agents; Taste; Taste Buds}, Month = {08}, Number = {7667}, Pages = {330-333}, Pmc = {PMC5805144}, pmid = {28792937}, Pst = {ppublish}, Title = {Rewiring the taste system}, Volume = {548}, Year = {2017}, url = {papers/Lee_Nature2017.pdf}, Bdsk-File-2 = {papers/Lee_Nature2017a.pdf}} @book{Kennedy:2016, Annote = {LDR 00863nam 22002535i 4500 001 18959929 005 20160203092018.0 008 160203s2016 nyu 000 0 eng 906 $a0$bibc$corignew$d2$eepcn$f20$gy-gencatlg 925 0 $aacquire$b1 shelf copy$xpolicy default 955 $apc17 2016-02-03 010 $a 2016932376 020 $a9783319277769 (alk. paper) 040 $aDLC$beng$erda$cDLC 042 $apcc 100 1 $aKennedy, Henry. 245 10 $aMicro-, meso- and macro-connectomics of the brain /$cHenry Kennedy. 263 $a1602 264 1 $aNew York, NY :$bSpringer Berlin Heidelberg,$c2016. 300 $apages cm 336 $atext$btxt$2rdacontent 337 $aunmediated$bn$2rdamedia 338 $avolume$bnc$2rdacarrier 963 $aRahila Nahid K; phone: (44) 43950500; email: N.Rahila@spi-global.com; bc: reinhold.joest@springer.com }, Author = {Kennedy, Henry}, Date-Added = {2018-02-13 23:56:07 +0000}, Date-Modified = {2018-02-13 23:58:08 +0000}, Isbn = {9783319277769 (alk. paper)}, Library-Id = {2016932376}, Title = {Micro-, meso- and macro-connectomics of the brain}, url = {papers/Bookshelf_NBK435763.pdf}} @article{Mergenthaler:2013, Abstract = {The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease.}, Author = {Mergenthaler, Philipp and Lindauer, Ute and Dienel, Gerald A and Meisel, Andreas}, Date-Added = {2018-01-25 01:38:17 +0000}, Date-Modified = {2018-01-25 01:38:17 +0000}, Doi = {10.1016/j.tins.2013.07.001}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {apoptosis; brain-body axis; glucose metabolism; metabolic brain disease; metabolic coupling}, Mesh = {Animals; Brain; Energy Metabolism; Glucose; Humans}, Month = {Oct}, Number = {10}, Pages = {587-97}, Pmc = {PMC3900881}, pmid = {23968694}, Pst = {ppublish}, Title = {Sugar for the brain: the role of glucose in physiological and pathological brain function}, Volume = {36}, Year = {2013}, url = {papers/Mergenthaler_TrendsNeurosci2013.pdf}} @article{Gordon:2008, Abstract = {Calcium signalling in astrocytes couples changes in neural activity to alterations in cerebral blood flow by eliciting vasoconstriction or vasodilation of arterioles. However, the mechanism for how these opposite astrocyte influences provide appropriate changes in vessel tone within an environment that has dynamic metabolic requirements remains unclear. Here we show that the ability of astrocytes to induce vasodilations over vasoconstrictions relies on the metabolic state of the rat brain tissue. When oxygen availability is lowered and astrocyte calcium concentration is elevated, astrocyte glycolysis and lactate release are maximized. External lactate attenuates transporter-mediated uptake from the extracellular space of prostaglandin E(2), leading to accumulation and subsequent vasodilation. In conditions of low oxygen concentration extracellular adenosine also increases, which blocks astrocyte-mediated constriction, facilitating dilation. These data reveal the role of metabolic substrates in regulating brain blood flow and provide a mechanism for differential astrocyte control over cerebrovascular diameter during different states of brain activation.}, Author = {Gordon, Grant R J and Choi, Hyun B and Rungta, Ravi L and Ellis-Davies, Graham C R and MacVicar, Brian A}, Date-Added = {2018-01-25 01:34:21 +0000}, Date-Modified = {2018-01-25 01:34:21 +0000}, Doi = {10.1038/nature07525}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Adenosine; Animals; Arterioles; Astrocytes; Brain; Dinoprostone; Glycolysis; Lactic Acid; Male; Organic Anion Transporters; Oxygen; Pressure; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Sprague-Dawley; Vasoconstriction; Vasodilation; Vasodilator Agents}, Month = {Dec}, Number = {7223}, Pages = {745-9}, Pmc = {PMC4097022}, pmid = {18971930}, Pst = {ppublish}, Title = {Brain metabolism dictates the polarity of astrocyte control over arterioles}, Volume = {456}, Year = {2008}, url = {papers/Gordon_Nature2008.pdf}, Bdsk-File-2 = {papers/Gordon_Nature2008a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07525}} @article{Pouchelon:2012, Abstract = {The topographical mapping of input is a fundamental organizing principle of sensory pathways. In the somatosensory system, a precise topographical representation of the face is first generated in the brainstem and then faithfully replicated in the thalamus and cortex. Although our knowledge of the distinct polysynaptic pathways that link cutaneous mechanoreceptors of the face with neocortical neurons has recently expanded, the molecular mechanisms controlling their neuron-type-specific assembly during development remain poorly understood. The increasing availability of genetic tools that enable manipulation of these developing circuits with cellular resolution now opens new perspectives in our understanding of the molecular mechanisms through which input from the periphery is converted into patterned central pathways.}, Annote = {somatosensory pathways only review. No information on visual system developmental innervation. - E12.5 Trigeminal axons innervate whisker follicle - E14.5 trigeminal collaterals reach PrV (principal nucleus of brainstem trigeminal complex) - E15.5 PrV axons reach VP (ventral posterior medial nucleus of thalamus) - E18 VP axons reach cortical subplate - P0 PrV axons branch into VP - P3 VP axons branch into L4 of S1 neocortex }, Author = {Pouchelon, Gabrielle and Frangeul, Laura and Rijli, Filippo M and Jabaudon, Denis}, Date-Added = {2018-01-25 01:03:08 +0000}, Date-Modified = {2018-01-25 01:18:14 +0000}, Doi = {10.1111/j.1460-9568.2012.08059.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Mesh = {Afferent Pathways; Animals; Brain Mapping; Humans; Models, Neurological; Neurons; Somatosensory Cortex; Thalamus; Vibrissae}, Month = {May}, Number = {10}, Pages = {1533-9}, pmid = {22606999}, Pst = {ppublish}, Title = {Patterning of pre-thalamic somatosensory pathways}, Volume = {35}, Year = {2012}, url = {papers/Pouchelon_EurJNeurosci2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2012.08059.x}} @article{Jabaudon:2012, Abstract = {Neurons in layer IV of the rodent whisker somatosensory cortex are tangentially organized in periodic clusters called barrels, each of which is innervated by thalamocortical axons transmitting sensory information from a single principal whisker, together forming a somatotopic map of the whisker pad. Proper thalamocortical innervation is critical for barrel formation during development, but the molecular mechanisms controlling layer IV neuron clustering are unknown. Here, we investigate the role in this mapping of the nuclear orphan receptor RORβ, which is expressed in neurons in layer IV during corticogenesis. We find that RORβ protein expression specifically increases in the whisker barrel cortex during barrel formation and that in vivo overexpression of RORβ is sufficient to induce periodic barrel-like clustering of cortical neurons. Remarkably, this clustering can be induced as early as E18, prior to innervation by thalamocortical afferents and whisker derived-input. At later developmental stages, these ectopic neuronal clusters are specifically innervated by thalamocortical axons, demonstrated by anterograde labeling from the thalamus and by expression of thalamocortical-specific synaptic markers. Together, these data indicate that RORβ expression levels control cytoarchitectural patterning of neocortical neurons during development, a critical process for the topographical mapping of whisker input onto the cortical surface.}, Author = {Jabaudon, Denis and Shnider, Sara J and Tischfield, David J and Galazo, Maria J and Macklis, Jeffrey D}, Date-Added = {2018-01-25 00:22:07 +0000}, Date-Modified = {2018-01-25 00:22:07 +0000}, Doi = {10.1093/cercor/bhr182}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Body Patterning; Fluorescent Antibody Technique; Mice; Mice, Transgenic; Microscopy, Confocal; Neocortex; Neurogenesis; Neurons; Nuclear Receptor Subfamily 1, Group F, Member 2; Somatosensory Cortex; Vibrissae}, Month = {May}, Number = {5}, Pages = {996-1006}, Pmc = {PMC3328343}, pmid = {21799210}, Pst = {ppublish}, Title = {RORβ induces barrel-like neuronal clusters in the developing neocortex}, Volume = {22}, Year = {2012}, url = {papers/Jabaudon_CerebCortex2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhr182}} @article{Bressler:1996, Abstract = {The primary visual cortex (V1) is part of a highly interconnected network of cortical areas, hierarchically organized but operating concurrently across hierarchical levels. The high degree of reciprocal interconnection among visual cortical areas provides a framework for their interaction during the performance of visual scene analysis. The functional interdependency of visual cortical areas which develops during scene analysis can be investigated by techniques which measure interareal correlated activity. Evidence from monkeys performing a visual pattern discrimination suggests that synchronization of aperiodic activity from neuronal ensembles in cortical areas at different hierarchical levels is a relevant aspect of visual function. The near-periodic nature of the synchronized response to moving light bars in earlier studies may have been a result of the type of stimulus used. Various models of visual cortex are discussed in which interareal synchronization plays a functional role.}, Author = {Bressler, S L}, Date-Added = {2018-01-25 00:05:15 +0000}, Date-Modified = {2018-01-25 00:07:08 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Keywords = {functional connectivity; oscillations; synchrony; Neocortex; isocortex; cerebral; areas}, Mesh = {Animals; Cats; Feedback; Haplorhini; Humans; Models, Neurological; Neurophysiology; Time Factors; Visual Cortex; Visual Pathways}, Month = {Apr}, Number = {1-2}, Pages = {37-49}, pmid = {8734042}, Pst = {ppublish}, Title = {Interareal synchronization in the visual cortex}, Volume = {76}, Year = {1996}, url = {papers/Bressler_BehavBrainRes1996.pdf}} @article{Rumberger:2001, Abstract = {We have qualitatively and quantitatively analysed the anatomical connections within and between rat primary visual cortex (V1) and the rim region surrounding area V1, using both ortho- and retrograde anatomical tracers (biotinylated dextran amine, biocytin, cholera toxin b subunit). From the analysis of the projection patterns, and with the assumption that single points in the rat visual cortex, as in other species, have projection fields made up of multiple patches of terminals, we have concluded that just two V1 recipient areas occupy the entire rim region: an anterolateral area, probably homologous with V2 in other mammals, previously named Oc2L, and a medial area, corresponding to Oc2M. A non-reciprocal projection from the anterolateral area to the medial area was identified. Small injections (300-600microm uptake zone diameter) of the anatomical tracers in area V1, or in the rim region, label orthograde intra-areal connections from each injection site to offset small patches. This is found in all regions of the rim and within at least the relatively expanded central dorsal field representation of V1. From the extent of these projections in V1 and the two rim regions, we have estimated that the neurons at the injection site send diverging laterally spreading projections to other neurons whose receptive fields share any part of the area included in the pooled receptive fields of the neurons at the injection site. Orthogradely labelled inter-areal feedforward projections from V1 to either rim region are estimated to diverge in their projections to neurons that share any part of the area of the pooled receptive fields of the V1 intra-areal connectional field of the same injection. The orthogradely labelled feedback projections to V1, from injection sites in either rim region, reach V1 neurons whose pooled receptive fields match those of the neurons in the rim injection site, i.e. with no divergence. Despite patchy anatomical connectional fields, our estimates indicate that visual space is represented continuously in the receptive fields of neurons postsynaptic to each intra- or inter-areal field of orthograde label. We suggest that, despite the absence of regularly mapped functions in rat V1 (e.g. regularly arranged orientation specificity), which in other species (e.g. primates and cats) relate to the patchy connectional patterns, the rat visual cortex intra- and inter-areal anatomical connections follow similar patterns and scaling factors to those in other species.}, Author = {Rumberger, A and Tyler, C J and Lund, J S}, Date-Added = {2018-01-25 00:04:07 +0000}, Date-Modified = {2018-01-25 00:04:07 +0000}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Mesh = {Animals; Biotin; Brain Mapping; Corpus Callosum; Dextrans; Female; Fluorescent Dyes; Lysine; Neural Pathways; Neurons; Rats; Rats, Long-Evans; Visual Cortex; Visual Perception}, Number = {1}, Pages = {35-52}, pmid = {11226668}, Pst = {ppublish}, Title = {Intra- and inter-areal connections between the primary visual cortex V1 and the area immediately surrounding V1 in the rat}, Volume = {102}, Year = {2001}, url = {papers/Rumberger_Neuroscience2001.pdf}} @article{Yamashita:2013, Abstract = {Primary sensory cortex discriminates incoming sensory information and generates multiple processing streams toward other cortical areas. However, the underlying cellular mechanisms remain unknown. Here, by making whole-cell recordings in primary somatosensory barrel cortex (S1) of behaving mice, we show that S1 neurons projecting to primary motor cortex (M1) and those projecting to secondary somatosensory cortex (S2) have distinct intrinsic membrane properties and exhibit markedly different membrane potential dynamics during behavior. Passive tactile stimulation evoked faster and larger postsynaptic potentials (PSPs) in M1-projecting neurons, rapidly driving phasic action potential firing, well-suited for stimulus detection. Repetitive active touch evoked strongly depressing PSPs and only transient firing in M1-projecting neurons. In contrast, PSP summation allowed S2-projecting neurons to robustly signal sensory information accumulated during repetitive touch, useful for encoding object features. Thus, target-specific transformation of sensory-evoked synaptic potentials by S1 projection neurons generates functionally distinct output signals for sensorimotor coordination and sensory perception.}, Author = {Yamashita, Takayuki and Pala, Aur{\'e}lie and Pedrido, Leticia and Kremer, Yves and Welker, Egbert and Petersen, Carl C H}, Date-Added = {2018-01-25 00:02:40 +0000}, Date-Modified = {2018-01-25 00:02:40 +0000}, Doi = {10.1016/j.neuron.2013.10.059}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Action Potentials; Afferent Pathways; Animals; Male; Mice; Motor Cortex; Neural Pathways; Neurons; Physical Stimulation; Somatosensory Cortex; Synaptic Potentials; Touch Perception}, Month = {Dec}, Number = {6}, Pages = {1477-90}, pmid = {24360548}, Pst = {ppublish}, Title = {Membrane potential dynamics of neocortical projection neurons driving target-specific signals}, Volume = {80}, Year = {2013}, url = {papers/Yamashita_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.10.059}} @article{Petersen:2013, Abstract = {Computations in neocortical circuits are predominantly driven by synaptic integration of excitatory glutamatergic and inhibitory GABAergic inputs. New optical, electrophysiological, and genetic methods allow detailed in vivo investigation of the superficial neocortical layers 2 and 3 (L2/3). Here, we review current knowledge of mouse L2/3 sensory cortex, focusing on somatosensory barrel cortex with comparisons to visual and auditory cortex. Broadly tuned, dense subthreshold synaptic input accompanied by sparse action potential (AP) firing in excitatory neurons provides a simple and reliable neural code useful for associative learning. Sparse AP firing is enforced by strong inhibition from genetically defined classes of GABAergic neurons. Subnetworks of strongly and specifically connected excitatory neurons may drive L2/3 network function, with potential contributions from dendritic spikes evoked by spatiotemporally clustered synaptic input. These functional properties of L2/3 are under profound regulation by brain state and behavior, providing interesting avenues for future mechanistic investigations into context-specific processing of sensory information.}, Author = {Petersen, Carl C H and Crochet, Sylvain}, Date-Added = {2018-01-25 00:02:39 +0000}, Date-Modified = {2018-01-25 00:02:39 +0000}, Doi = {10.1016/j.neuron.2013.03.020}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Action Potentials; Afferent Pathways; Animals; Mice; Neocortex; Nerve Net; Neurons; Sensation; Synaptic Transmission}, Month = {Apr}, Number = {1}, Pages = {28-48}, pmid = {23583106}, Pst = {ppublish}, Title = {Synaptic computation and sensory processing in neocortical layer 2/3}, Volume = {78}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.03.020}} @article{Bavelier:2002, Abstract = {Animal studies have shown that sensory deprivation in one modality can have striking effects on the development of the remaining modalities. Although recent studies of deaf and blind humans have also provided convincing behavioural, electrophysiological and neuroimaging evidence of increased capabilities and altered organization of spared modalities, there is still much debate about the identity of the brain systems that are changed and the mechanisms that mediate these changes. Plastic changes across brain systems and related behaviours vary as a function of the timing and the nature of changes in experience. This specificity must be understood in the context of differences in the maturation rates and timing of the associated critical periods, differences in patterns of transiently existing connections, and differences in molecular factors across brain systems.}, Author = {Bavelier, Daphne and Neville, Helen J}, Date-Added = {2018-01-25 00:00:21 +0000}, Date-Modified = {2018-01-25 00:00:21 +0000}, Doi = {10.1038/nrn848}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Brain; Cell Differentiation; Humans; Neural Pathways; Neuronal Plasticity; Neurons; Sensation; Sensory Deprivation; Synapses}, Month = {Jun}, Number = {6}, Pages = {443-52}, pmid = {12042879}, Pst = {ppublish}, Title = {Cross-modal plasticity: where and how?}, Volume = {3}, Year = {2002}, url = {papers/Bavelier_NatRevNeurosci2002.pdf}} @article{Tagge:2018, Abstract = {The mechanisms underpinning concussion, traumatic brain injury, and chronic traumatic encephalopathy, and the relationships between these disorders, are poorly understood. We examined post-mortem brains from teenage athletes in the acute-subacute period after mild closed-head impact injury and found astrocytosis, myelinated axonopathy, microvascular injury, perivascular neuroinflammation, and phosphorylated tau protein pathology. To investigate causal mechanisms, we developed a mouse model of lateral closed-head impact injury that uses momentum transfer to induce traumatic head acceleration. Unanaesthetized mice subjected to unilateral impact exhibited abrupt onset, transient course, and rapid resolution of a concussion-like syndrome characterized by altered arousal, contralateral hemiparesis, truncal ataxia, locomotor and balance impairments, and neurobehavioural deficits. Experimental impact injury was associated with axonopathy, blood-brain barrier disruption, astrocytosis, microgliosis (with activation of triggering receptor expressed on myeloid cells, TREM2), monocyte infiltration, and phosphorylated tauopathy in cerebral cortex ipsilateral and subjacent to impact. Phosphorylated tauopathy was detected in ipsilateral axons by 24 h, bilateral axons and soma by 2 weeks, and distant cortex bilaterally at 5.5 months post-injury. Impact pathologies co-localized with serum albumin extravasation in the brain that was diagnostically detectable in living mice by dynamic contrast-enhanced MRI. These pathologies were also accompanied by early, persistent, and bilateral impairment in axonal conduction velocity in the hippocampus and defective long-term potentiation of synaptic neurotransmission in the medial prefrontal cortex, brain regions distant from acute brain injury. Surprisingly, acute neurobehavioural deficits at the time of injury did not correlate with blood-brain barrier disruption, microgliosis, neuroinflammation, phosphorylated tauopathy, or electrophysiological dysfunction. Furthermore, concussion-like deficits were observed after impact injury, but not after blast exposure under experimental conditions matched for head kinematics. Computational modelling showed that impact injury generated focal point loading on the head and seven-fold greater peak shear stress in the brain compared to blast exposure. Moreover, intracerebral shear stress peaked before onset of gross head motion. By comparison, blast induced distributed force loading on the head and diffuse, lower magnitude shear stress in the brain. We conclude that force loading mechanics at the time of injury shape acute neurobehavioural responses, structural brain damage, and neuropathological sequelae triggered by neurotrauma. These results indicate that closed-head impact injuries, independent of concussive signs, can induce traumatic brain injury as well as early pathologies and functional sequelae associated with chronic traumatic encephalopathy. These results also shed light on the origins of concussion and relationship to traumatic brain injury and its aftermath.awx350media15713427811001.}, Author = {Tagge, Chad A and Fisher, Andrew M and Minaeva, Olga V and Gaudreau-Balderrama, Amanda and Moncaster, Juliet A and Zhang, Xiao-Lei and Wojnarowicz, Mark W and Casey, Noel and Lu, Haiyan and Kokiko-Cochran, Olga N and Saman, Sudad and Ericsson, Maria and Onos, Kristen D and Veksler, Ronel and Senatorov, Jr, Vladimir V and Kondo, Asami and Zhou, Xiao Z and Miry, Omid and Vose, Linnea R and Gopaul, Katisha R and Upreti, Chirag and Nowinski, Christopher J and Cantu, Robert C and Alvarez, Victor E and Hildebrandt, Audrey M and Franz, Erich S and Konrad, Janusz and Hamilton, James A and Hua, Ning and Tripodis, Yorghos and Anderson, Andrew T and Howell, Gareth R and Kaufer, Daniela and Hall, Garth F and Lu, Kun P and Ransohoff, Richard M and Cleveland, Robin O and Kowall, Neil W and Stein, Thor D and Lamb, Bruce T and Huber, Bertrand R and Moss, William C and Friedman, Alon and Stanton, Patric K and McKee, Ann C and Goldstein, Lee E}, Date-Added = {2018-01-24 23:58:35 +0000}, Date-Modified = {2018-01-24 23:58:35 +0000}, Doi = {10.1093/brain/awx350}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {TREM2; chronic traumatic encephalopathy; concussion; tau protein; traumatic brain injury}, Month = {Jan}, pmid = {29360998}, Pst = {aheadofprint}, Title = {Concussion, microvascular injury, and early tauopathy in young athletes after impact head injury and an impact concussion mouse model}, Year = {2018}, url = {papers/Tagge_Brain2018.pdf}} @article{Li:2002d, Abstract = {We examined whether Gbx2 is required after embryonic day 9 (E9) to repress Otx2 in the cerebellar anlage and position the midbrain/hindbrain organizer. In contrast to Gbx2 null mutants, mice lacking Gbx2 in rhombomere 1 (r1) after E9 (Gbx2-CKO) are viable and develop a cerebellum. A Gbx2-independent pathway can repress Otx2 in r1 after E9. Mid/hindbrain organizer gene expression, however, continues to be dependent on Gbx2. We found that Fgf8 expression normally correlates with the isthmus where cells undergo low proliferation and that in Gbx2-CKO mutants this domain is expanded. We propose that Fgf8 permits lateral cerebellar development through repression of Otx2 and also suppresses medial cerebellar growth in Gbx2-CKO embryos. Our work has uncovered distinct requirements for Gbx2 during cerebellum formation and provided a model for how a transcription factor can play multiple roles during development.}, Author = {Li, James Y H and Lao, Zhimin and Joyner, Alexandra L}, Date-Added = {2018-01-24 23:14:27 +0000}, Date-Modified = {2018-01-24 23:14:27 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Body Patterning; Cell Differentiation; Cerebellum; Female; Fetus; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mesencephalon; Mice; Mice, Knockout; Nerve Tissue Proteins; Otx Transcription Factors; Proto-Oncogene Proteins; Rhombencephalon; Trans-Activators; Wnt Proteins; Zebrafish Proteins}, Month = {Sep}, Number = {1}, Pages = {31-43}, pmid = {12367504}, Pst = {ppublish}, Title = {Changing requirements for Gbx2 in development of the cerebellum and maintenance of the mid/hindbrain organizer}, Volume = {36}, Year = {2002}, url = {papers/Li_Neuron2002.pdf}} @article{Cuoco:2017, Abstract = {C57BL/6 mice exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the posterior vermis, indicative of neuronal migration defect during cerebellar development. Recognizing that many genetically engineered (GE) mouse lines are produced from C57BL/6 ES cells or backcrossed to this strain, we performed histological analyses and found that cerebellar heterotopia were a common feature present in the majority of GE lines on this background. Furthermore, we identify GE mouse lines that will be valuable in the study of cerebellar malformations including diverse driver, reporter, and optogenetic lines. Finally, we discuss the implications that these data have on the use of C57BL/6 mice and GE mice on this background in studies of cerebellar development or as models of disease.}, Author = {Cuoco, Joshua A and Esposito, Anthony W and Moriarty, Shannon and Tang, Ying and Seth, Sonika and Toia, Alyssa R and Kampton, Elias B and Mayr, Yevgeniy and Khan, Mussarah and Khan, Mohammad B and Mullen, Brian R and Ackman, James B and Siddiqi, Faez and Wolfe, John H and Savinova, Olga V and Ramos, Raddy L}, Date-Added = {2018-01-19 23:05:48 +0000}, Date-Modified = {2018-01-19 23:05:48 +0000}, Doi = {10.1007/s12311-017-0892-3}, Journal = {Cerebellum}, Journal-Full = {Cerebellum (London, England)}, Keywords = {C57BL/6; Cerebellar development; Knock-out mice; Transgenic mice}, Month = {Oct}, pmid = {29043563}, Pst = {aheadofprint}, Title = {Malformation of the Posterior Cerebellar Vermis Is a Common Neuroanatomical Phenotype of Genetically Engineered Mice on the C57BL/6 Background}, Year = {2017}, url = {papers/Cuoco_Cerebellum2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s12311-017-0892-3}} @article{Murabe:1983, Abstract = {Immunohistochemical studies with the use of the peroxidase-antiperoxidase (PAP) method revealed that "amoeboid microglial cells", in the brains of neonatal rats and "brain macrophages" in lesioned brains of adult rats react positively to an antiserum raised against macrophages. In brains of neonatal rats, "amoeboid microglial cells" stained by means of the PAP-method were observed in the corpus callosum, internal capsule, dorso-lateral region of the thalamus, subventricular zone of the lateral ventricle, and the subependymal layer of the ventricular system. These cellular elements were not detected in brains of rats aged 21 days or older. Resting microglial cells displaying a typical ramified structure were not specifically stained. Cells reacting positively to the macrophage antiserum appeared (i) in the cerebral cortex of adult rats following placement of a stab wound, or (ii) in the hippocampal formation after kainic acid-induced lesions; in the damaged areas immunoreactive cells exhibited the typical features of "brain macrophages". "Brain macrophages" and "amoeboid microglial cells" are considered to belong to the class of exudate macrophages derived from blood monocytes. Thus, elements of hematogenous origin do exist in the intact brain parenchyma of neonatal rats and in lesioned brains of adult rats. The relationship between brain macrophages and resting microglial cells is discussed.}, Author = {Murabe, Y and Sano, Y}, Date-Added = {2018-01-18 00:40:34 +0000}, Date-Modified = {2018-01-18 00:40:34 +0000}, Journal = {Cell Tissue Res}, Journal-Full = {Cell and tissue research}, Mesh = {Animals; Animals, Newborn; Brain; Immunoenzyme Techniques; Macrophages; Neuroglia; Rats}, Number = {1}, Pages = {85-95}, pmid = {6339067}, Pst = {ppublish}, Title = {Morphological studies on neuroglia. VII. Distribution of "brain macrophages" in brains of neonatal and adult rats, as determined by means of immunohistochemistry}, Volume = {229}, Year = {1983}} @article{Reep:1988, Abstract = {The cerebral isocortex is usually considered to be a 6-layered structure. Our anatomical findings suggest that layer VII be recognized as a distinct entity in rodent isocortex. This conclusion is based on cytoarchitectural, fiberarchitectural, connectional and developmental data.}, Author = {Reep, R L and Goodwin, G S}, Date-Added = {2018-01-18 00:39:05 +0000}, Date-Modified = {2018-01-18 00:39:05 +0000}, Journal = {Neurosci Lett}, Journal-Full = {Neuroscience letters}, Mesh = {Animals; Cerebral Cortex; Fluorescent Dyes; Leucine; Rats; Somatosensory Cortex; Stilbamidines; Visual Cortex}, Month = {Jul}, Number = {1-2}, Pages = {15-20}, pmid = {3412636}, Pst = {ppublish}, Title = {Layer VII of rodent cerebral cortex}, Volume = {90}, Year = {1988}, url = {papers/Reep_NeurosciLett1988.pdf}} @article{Selverston:1998, Abstract = {The lobster stomatogastric ganglion contains 30 neurons and when modulated can produce two distinct rhythmic motor patterns--the gastric mill and the pyloric. The complete neural circuitry underlying both patterns is well known. Without modulatory input no patterns are produced, and the neurons fire tonically or are silent. When neuromodulators are released into the ganglion from specific neurons or are delivered as hormones, the properties of the neurons and synapses change dramatically and modulator-specific gastric mill and pyloric patterns are produced. In general the rhythmicity derives from the induced burstiness of the neurons, and the pattern from the strengths of the electrical and chemical synapses. The organized activity can be traced to a marked reduction of chaotic activity in individual neurons when they shift from the unmodulated to the modulated state.}, Author = {Selverston, A and Elson, R and Rabinovich, M and Huerta, R and Abarbanel, H}, Date-Added = {2018-01-17 00:03:58 +0000}, Date-Modified = {2018-01-17 00:03:58 +0000}, Journal = {Ann N Y Acad Sci}, Journal-Full = {Annals of the New York Academy of Sciences}, Mesh = {Animals; Ganglia, Invertebrate; Motor Neurons; Nephropidae; Nervous System Physiological Phenomena; Periodicity; Stomach}, Month = {Nov}, Pages = {35-50}, pmid = {9928300}, Pst = {ppublish}, Title = {Basic principles for generating motor output in the stomatogastric ganglion}, Volume = {860}, Year = {1998}, url = {papers/Selverston_AnnNYAcadSci1998.pdf}} @article{Bliss:1973a, Abstract = {1. Potential changes evoked by stimulation of the perforant path have been recorded in the dentate area of the hippocampal formation in chronically prepared unanaesthetized rabbits.2. Components attributed to excitatory synaptic current flow and to action potentials in the granule cell population were distinguishable, with characteristics largely the same as in anaesthetized rabbits.3. Stimulation at 15/sec for several seconds usually led to the granule cells being more effectively activated by the individual stimuli of the train (;frequency potentiation'). Single stimuli then commonly produced multiple discharges in the granule cell population.4. After single periods of stimulation at 15/sec for 15-20 sec there was on 26% of the occasions (41% of those on which there was good frequency potentiation) a long-lasting potentiation of the responses to subsequent stimuli, lasting from 1 hr to 3 days.5. After a further 20% of the periods of repetitive stimulation there was a shorter lasting potentiation, and after 8% there was a short lasting depression.6. The potentiation, when present, was characterized by some or all of the following changes: increases in the amplitudes of the synaptic wave and population spike, reduction in the latency of the population spike, and reductions in the variability of the characteristics of the population spike.7. During the long-lasting potentiation there was an increase in the excitability of the post-synaptic cells and, on some but not all occasions, an increase in the extracellular current flow produced directly by synaptic action.}, Author = {Bliss, T V and Gardner-Medwin, A R}, Date-Added = {2018-01-17 00:01:47 +0000}, Date-Modified = {2018-01-17 00:01:47 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Action Potentials; Animals; Electric Stimulation; Electrodes, Implanted; Electrophysiology; Evoked Potentials; Hippocampus; Microelectrodes; Neurons; Online Systems; Rabbits; Synapses; Time Factors}, Month = {Jul}, Number = {2}, Pages = {357-74}, Pmc = {PMC1350459}, pmid = {4727085}, Pst = {ppublish}, Title = {Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path}, Volume = {232}, Year = {1973}} @article{Bliss:1973, Abstract = {1. The after-effects of repetitive stimulation of the perforant path fibres to the dentate area of the hippocampal formation have been examined with extracellular micro-electrodes in rabbits anaesthetized with urethane.2. In fifteen out of eighteen rabbits the population response recorded from granule cells in the dentate area to single perforant path volleys was potentiated for periods ranging from 30 min to 10 hr after one or more conditioning trains at 10-20/sec for 10-15 sec, or 100/sec for 3-4 sec.3. The population response was analysed in terms of three parameters: the amplitude of the population excitatory post-synaptic potential (e.p.s.p.), signalling the depolarization of the granule cells, and the amplitude and latency of the population spike, signalling the discharge of the granule cells.4. All three parameters were potentiated in 29% of the experiments; in other experiments in which long term changes occurred, potentiation was confined to one or two of the three parameters. A reduction in the latency of the population spike was the commonest sign of potentiation, occurring in 57% of all experiments. The amplitude of the population e.p.s.p. was increased in 43%, and of the population spike in 40%, of all experiments.5. During conditioning at 10-20/sec there was massive potentiation of the population spike (;frequency potentiation'). The spike was suppressed during stimulation at 100/sec. Both frequencies produced long-term potentiation.6. The results suggest that two independent mechanisms are responsible for long-lasting potentiation: (a) an increase in the efficiency of synaptic transmission at the perforant path synapses; (b) an increase in the excitability of the granule cell population.}, Author = {Bliss, T V and Lomo, T}, Date-Added = {2018-01-17 00:01:45 +0000}, Date-Modified = {2018-01-17 00:01:45 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Action Potentials; Anesthesia, Intravenous; Animals; Electric Stimulation; Electrophysiology; Evoked Potentials; Female; Hippocampus; Male; Microelectrodes; Neurons; Rabbits; Synapses; Time Factors}, Month = {Jul}, Number = {2}, Pages = {331-56}, Pmc = {PMC1350458}, pmid = {4727084}, Pst = {ppublish}, Title = {Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path}, Volume = {232}, Year = {1973}, url = {papers/Bliss_JPhysiol1973.pdf}} @article{Brown:1914, Author = {Brown, T G}, Date-Added = {2018-01-16 23:59:23 +0000}, Date-Modified = {2018-01-16 23:59:23 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Month = {Mar}, Number = {1}, Pages = {18-46}, Pmc = {PMC1420503}, pmid = {16993247}, Pst = {ppublish}, Title = {On the nature of the fundamental activity of the nervous centres; together with an analysis of the conditioning of rhythmic activity in progression, and a theory of the evolution of function in the nervous system}, Volume = {48}, Year = {1914}, url = {papers/Brown_JPhysiol1914.pdf}} @article{Sherrington:1913, Abstract = {IN a previous paper' an attempt was made to determine factors at work in the reflex act of stepping, that is to say in the stepping performed by a purely reflex preparation, either decerebrate or purely spinal. The present experiments are in contribution toward the same problem. Method. In the present experiments the mode of evoking the rhythmic reflex has been that recently found by T. Graham Browns, A. Forbes3, and myself4; and the reflex preparation employed has consisted of an isolated pair of symmetrical extensor muscles5, i.e. the main extensor muscle of each knee, right and left, in the decerebrate mammal (cat).}, Author = {Sherrington, C S}, Date-Added = {2018-01-16 23:56:57 +0000}, Date-Modified = {2018-01-16 23:57:30 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Month = {Nov}, Number = {3}, Pages = {196-214}, Pmc = {PMC1420464}, pmid = {16993214}, Pst = {ppublish}, Title = {Further observations on the production of reflex stepping by combination of reflex excitation with reflex inhibition}, Volume = {47}, Year = {1913}, url = {papers/Sherrington_JPhysiol1913.pdf}} @article{Drew:2008, Abstract = {Spontaneous ultra-slow oscillations in brain signals are ubiquitous, although their source and function remain unknown. A new study now reports that this activity is correlated between functionally related areas across hemispheres in humans.}, Author = {Drew, Patrick J and Duyn, Jeff H and Golanov, Eugene and Kleinfeld, David}, Date-Added = {2018-01-16 23:49:59 +0000}, Date-Modified = {2018-01-16 23:50:39 +0000}, Doi = {10.1038/nn0908-991}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {teaching; facts; oscillations; synchrony; EEG; LFP; neurophysiology}, Mesh = {Biological Clocks; Brain; Electroencephalography; Functional Laterality; Humans; Magnetic Resonance Imaging; Models, Neurological}, Month = {Sep}, Number = {9}, Pages = {991-3}, pmid = {18725901}, Pst = {ppublish}, Title = {Finding coherence in spontaneous oscillations}, Volume = {11}, Year = {2008}, url = {papers/Drew_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0908-991}} @article{Ramsden:2015, Abstract = {Neural circuits in the medial entorhinal cortex (MEC) encode an animal's position and orientation in space. Within the MEC spatial representations, including grid and directional firing fields, have a laminar and dorsoventral organization that corresponds to a similar topography of neuronal connectivity and cellular properties. Yet, in part due to the challenges of integrating anatomical data at the resolution of cortical layers and borders, we know little about the molecular components underlying this organization. To address this we develop a new computational pipeline for high-throughput analysis and comparison of in situ hybridization (ISH) images at laminar resolution. We apply this pipeline to ISH data for over 16,000 genes in the Allen Brain Atlas and validate our analysis with RNA sequencing of MEC tissue from adult mice. We find that differential gene expression delineates the borders of the MEC with neighboring brain structures and reveals its laminar and dorsoventral organization. We propose a new molecular basis for distinguishing the deep layers of the MEC and show that their similarity to corresponding layers of neocortex is greater than that of superficial layers. Our analysis identifies ion channel-, cell adhesion- and synapse-related genes as candidates for functional differentiation of MEC layers and for encoding of spatial information at different scales along the dorsoventral axis of the MEC. We also reveal laminar organization of genes related to disease pathology and suggest that a high metabolic demand predisposes layer II to neurodegenerative pathology. In principle, our computational pipeline can be applied to high-throughput analysis of many forms of neuroanatomical data. Our results support the hypothesis that differences in gene expression contribute to functional specialization of superficial layers of the MEC and dorsoventral organization of the scale of spatial representations.}, Author = {Ramsden, Helen L and S{\"u}rmeli, G{\"u}l{\c s}en and McDonagh, Steven G and Nolan, Matthew F}, Date-Added = {2018-01-16 23:48:30 +0000}, Date-Modified = {2018-01-16 23:48:57 +0000}, Doi = {10.1371/journal.pcbi.1004032}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {method; technique; connectivity; computational biology}, Mesh = {Animals; Entorhinal Cortex; Gene Expression Profiling; Image Processing, Computer-Assisted; Male; Mice; Mice, Inbred C57BL; Molecular Imaging; Organ Specificity}, Month = {Jan}, Number = {1}, Pages = {e1004032}, Pmc = {PMC4304787}, pmid = {25615592}, Pst = {epublish}, Title = {Laminar and dorsoventral molecular organization of the medial entorhinal cortex revealed by large-scale anatomical analysis of gene expression}, Volume = {11}, Year = {2015}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.1004032}} @article{Richardet:2015, Abstract = {MOTIVATION: In neuroscience, as in many other scientific domains, the primary form of knowledge dissemination is through published articles. One challenge for modern neuroinformatics is finding methods to make the knowledge from the tremendous backlog of publications accessible for search, analysis and the integration of such data into computational models. A key example of this is metascale brain connectivity, where results are not reported in a normalized repository. Instead, these experimental results are published in natural language, scattered among individual scientific publications. This lack of normalization and centralization hinders the large-scale integration of brain connectivity results. In this article, we present text-mining models to extract and aggregate brain connectivity results from 13.2 million PubMed abstracts and 630 216 full-text publications related to neuroscience. The brain regions are identified with three different named entity recognizers (NERs) and then normalized against two atlases: the Allen Brain Atlas (ABA) and the atlas from the Brain Architecture Management System (BAMS). We then use three different extractors to assess inter-region connectivity. RESULTS: NERs and connectivity extractors are evaluated against a manually annotated corpus. The complete in litero extraction models are also evaluated against in vivo connectivity data from ABA with an estimated precision of 78%. The resulting database contains over 4 million brain region mentions and over 100 000 (ABA) and 122 000 (BAMS) potential brain region connections. This database drastically accelerates connectivity literature review, by providing a centralized repository of connectivity data to neuroscientists.}, Author = {Richardet, Renaud and Chappelier, Jean-C{\'e}dric and Telefont, Martin and Hill, Sean}, Date-Added = {2018-01-16 23:48:28 +0000}, Date-Modified = {2018-01-16 23:48:57 +0000}, Doi = {10.1093/bioinformatics/btv025}, Journal = {Bioinformatics}, Journal-Full = {Bioinformatics (Oxford, England)}, Keywords = {method; technique; connectivity; computational biology}, Mesh = {Animals; Artificial Intelligence; Atlases as Topic; Brain; Brain Mapping; Data Mining; Databases, Factual; Mice; Neuroanatomy; Periodicals as Topic; Software; Terminology as Topic}, Month = {May}, Number = {10}, Pages = {1640-7}, Pmc = {PMC4426844}, pmid = {25609795}, Pst = {ppublish}, Title = {Large-scale extraction of brain connectivity from the neuroscientific literature}, Volume = {31}, Year = {2015}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/bioinformatics/btv025}} @article{Kuan:2015, Abstract = {The Allen Mouse Brain Connectivity Atlas is a mesoscale whole brain axonal projection atlas of the C57Bl/6J mouse brain. Anatomical trajectories throughout the brain were mapped into a common 3D space using a standardized platform to generate a comprehensive and quantitative database of inter-areal and cell-type-specific projections. This connectivity atlas has several desirable features, including brain-wide coverage, validated and versatile experimental techniques, a single standardized data format, a quantifiable and integrated neuroinformatics resource, and an open-access public online database (http://connectivity.brain-map.org/). Meaningful informatics data quantification and comparison is key to effective use and interpretation of connectome data. This relies on successful definition of a high fidelity atlas template and framework, mapping precision of raw data sets into the 3D reference framework, accurate signal detection and quantitative connection strength algorithms, and effective presentation in an integrated online application. Here we describe key informatics pipeline steps in the creation of the Allen Mouse Brain Connectivity Atlas and include basic application use cases.}, Author = {Kuan, Leonard and Li, Yang and Lau, Chris and Feng, David and Bernard, Amy and Sunkin, Susan M and Zeng, Hongkui and Dang, Chinh and Hawrylycz, Michael and Ng, Lydia}, Date-Added = {2018-01-16 23:48:26 +0000}, Date-Modified = {2018-01-16 23:48:57 +0000}, Doi = {10.1016/j.ymeth.2014.12.013}, Journal = {Methods}, Journal-Full = {Methods (San Diego, Calif.)}, Keywords = {Digital atlas; Image registration; Mouse connectivity atlas; Neuronal projection; Signal detection; method; technique; connectivity; computational biology}, Mesh = {Animals; Atlases as Topic; Brain; Brain Mapping; Humans; Informatics; Mice; Mice, Inbred C57BL}, Month = {Feb}, Pages = {4-17}, pmid = {25536338}, Pst = {ppublish}, Title = {Neuroinformatics of the Allen Mouse Brain Connectivity Atlas}, Volume = {73}, Year = {2015}, url = {papers/Kuan_Methods2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ymeth.2014.12.013}} @article{Ermentrout:2001, Abstract = {The theory of coupled phase oscillators provides a framework to understand the emergent properties of networks of neuronal oscillators. When the architecture of the network is dominated by short-range connections, the pattern of electrical output is predicted to correspond to traveling plane and rotating waves, in addition to synchronized output. We argue that this theory provides the foundation for understanding the traveling electrical waves that are observed across olfactory, visual, and visuomotor areas of cortex in a variety of species. The waves are typically present during periods outside of stimulation, while synchronous activity typically dominates in the presence of a strong stimulus. We suggest that the continuum of phase shifts during epochs with traveling waves provides a means to scan the incoming sensory stream for novel features. Experiments to test our theoretical approach are presented.}, Author = {Ermentrout, G B and Kleinfeld, D}, Date-Added = {2018-01-16 23:44:29 +0000}, Date-Modified = {2018-01-16 23:44:29 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Biological Clocks; Cerebral Cortex; Humans; Models, Neurological; Nerve Net; Neural Networks (Computer); Synaptic Transmission}, Month = {Jan}, Number = {1}, Pages = {33-44}, pmid = {11182079}, Pst = {ppublish}, Title = {Traveling electrical waves in cortex: insights from phase dynamics and speculation on a computational role}, Volume = {29}, Year = {2001}, url = {papers/Ermentrout_Neuron2001.pdf}} @article{Smith:2010a, Abstract = {BACKGROUND: Shortly after eye opening, initially disorganized visual cortex circuitry is rapidly refined to form smooth retinotopic maps. This process asymptotes long before adulthood, but it is unknown whether further refinement is possible. Prior work from our lab has shown that the retinotopic map of the non-dominant ipsilateral eye develops faster when the dominant contralateral eye is removed. We examined whether input from the contralateral eye might also limit the ultimate refinement of the ipsilateral eye retinotopic map in adults. In addition, we examined whether the increased refinement involved the recruitment of adjacent cortical area. METHODOLOGY/PRINCIPAL FINDINGS: By surgically implanting a chronic optical window over visual cortex in mice, we repeatedly measured the degree of retinotopic map refinement using quantitative intrinsic signal optical imaging over four weeks. We removed the contralateral eye and observed that the retinotopic map for the ipsilateral eye was further refined and the maximum magnitude of response increased. However, these changes were not accompanied by an increase in the area of responsive cortex. CONCLUSIONS/SIGNIFICANCE: Since the retinotopic map was functionally refined to a greater degree without taking over adjacent cortical area, we conclude that input from the contralateral eye limits the normal refinement of visual cortical circuitry in mice. These findings suggest that the refinement capacity of cortical circuitry is normally saturated.}, Author = {Smith, Spencer L and Trachtenberg, Joshua T}, Date-Added = {2018-01-16 23:41:35 +0000}, Date-Modified = {2018-01-16 23:41:35 +0000}, Doi = {10.1371/journal.pone.0009925}, Journal = {PLoS One}, Journal-Full = {PloS one}, Mesh = {Animals; Eye; Functional Laterality; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Photic Stimulation; Retina; Sensory Deprivation; Vision, Ocular; Visual Cortex; Visual Pathways}, Month = {Mar}, Number = {3}, Pages = {e9925}, Pmc = {PMC2848025}, pmid = {20369001}, Pst = {epublish}, Title = {The refinement of ipsilateral eye retinotopic maps is increased by removing the dominant contralateral eye in adult mice}, Volume = {5}, Year = {2010}, url = {papers/Smith_PLoSOne2010.pdf}} @article{Faguet:2009, Abstract = {In the cerebral cortex, neuronal circuits are first laid down by intrinsic mechanisms and then refined by experience. In the canonical model, this refinement is driven by activity-dependent competition between inputs for some limited cortical resource. Here we examine this idea in the mouse visual cortex at the peak of the critical period for experience-dependent plasticity. By imaging intrinsic optical responses, we mapped the strength and size of each eye's cortical representation in normal mice, mice that had been deprived of patterned vision uni- or bilaterally, and in mice in which the contralateral eye had been removed. We find that for both eyes, a period of visual deprivation results in a loss of cortical responsiveness to stimulation through the deprived eye. In addition, the ipsilateral eye pathway is affected by the quality of vision through the opposite eye. Our findings indicate that although both contra- and ipsilateral eye pathways require visual experience for their maintenance, ipsilateral eye projections bear an additional, unique sensitivity to binocular interactions.}, Author = {Faguet, Joshua and Maranhao, Bruno and Smith, Spencer L and Trachtenberg, Joshua T}, Date-Added = {2018-01-16 23:40:47 +0000}, Date-Modified = {2018-01-16 23:40:47 +0000}, Doi = {10.1152/jn.90893.2008}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Mesh = {Animals; Brain Mapping; Cholera Toxin; Diagnostic Imaging; Eye; Fourier Analysis; Functional Laterality; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Orientation; Photic Stimulation; Sensory Deprivation; Sensory Thresholds; Space Perception; Time Factors; Visual Cortex; Visual Pathways}, Month = {Feb}, Number = {2}, Pages = {855-61}, Pmc = {PMC2657065}, pmid = {19052109}, Pst = {ppublish}, Title = {Ipsilateral eye cortical maps are uniquely sensitive to binocular plasticity}, Volume = {101}, Year = {2009}, url = {papers/Faguet_JNeurophysiol2009.pdf}} @article{Kramer:2013, Abstract = {The optical neuroscience revolution is transforming how we study neural circuits. By providing a precise way to manipulate endogenous neuronal signaling proteins, it also has the potential to transform our understanding of molecular neuroscience. Recent advances in chemical biology have produced light-sensitive compounds that photoregulate a wide variety of proteins underlying signaling between and within neurons. Chemical tools for optopharmacology include caged agonists and antagonists and reversibly photoswitchable ligands. These reagents act on voltage-gated ion channels and neurotransmitter receptors, enabling control of neuronal signaling with a high degree of spatial and temporal precision. By covalently attaching photoswitch molecules to genetically tagged proteins, the newly emerging methodology of optogenetic pharmacology allows biochemically precise control in targeted subsets of neurons. Now that the tools for manipulating endogenous neuronal signaling proteins are available, they can be implemented in vivo to enhance our understanding of the molecular bases of brain function and dysfunctions.}, Author = {Kramer, Richard H and Mourot, Alexandre and Adesnik, Hillel}, Date-Added = {2018-01-16 23:37:48 +0000}, Date-Modified = {2018-01-16 23:38:11 +0000}, Doi = {10.1038/nn.3424}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {technique; method; optogenetics; activity manipulation}, Mesh = {Animals; Humans; Ion Channels; Ligands; Neurons; Optogenetics; Photic Stimulation; Receptors, Neurotransmitter; Signal Transduction}, Month = {Jul}, Number = {7}, Pages = {816-23}, Pmc = {PMC4963006}, pmid = {23799474}, Pst = {ppublish}, Title = {Optogenetic pharmacology for control of native neuronal signaling proteins}, Volume = {16}, Year = {2013}, url = {papers/Kramer_NatNeurosci2013.pdf}} @article{Czajkowski:2014, Abstract = {The retrosplenial cortex (RSC) is part of a network of interconnected cortical, hippocampal, and thalamic structures harboring spatially modulated neurons. The RSC contains head direction cells and connects to the parahippocampal region and anterior thalamus. Manipulations of the RSC can affect spatial and contextual tasks. A considerable amount of evidence implicates the role of the RSC in spatial navigation, but it is unclear whether this structure actually encodes or stores spatial information. We used a transgenic mouse in which the expression of green fluorescent protein was under the control of the immediate early gene c-fos promoter as well as time-lapse two-photon in vivo imaging to monitor neuronal activation triggered by spatial learning in the Morris water maze. We uncovered a repetitive pattern of cell activation in the RSC consistent with the hypothesis that during spatial learning an experience-dependent memory trace is formed in this structure. In support of this hypothesis, we also report three other observations. First, temporary RSC inactivation disrupts performance in a spatial learning task. Second, we show that overexpressing the transcription factor CREB in the RSC with a viral vector, a manipulation known to enhance memory consolidation in other circuits, results in spatial memory enhancements. Third, silencing the viral CREB-expressing neurons with the allatostatin system occludes the spatial memory enhancement. Taken together, these results indicate that the retrosplenial cortex engages in the formation and storage of memory traces for spatial information.}, Author = {Czajkowski, Rafa{\l} and Jayaprakash, Balaji and Wiltgen, Brian and Rogerson, Thomas and Guzman-Karlsson, Mikael C and Barth, Alison L and Trachtenberg, Joshua T and Silva, Alcino J}, Date-Added = {2018-01-16 23:37:16 +0000}, Date-Modified = {2018-01-16 23:37:16 +0000}, Doi = {10.1073/pnas.1313222111}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Cyclic AMP Response Element-Binding Protein; Green Fluorescent Proteins; Gyrus Cinguli; Hippocampus; Maze Learning; Memory; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton; Neurons; Promoter Regions, Genetic; Proto-Oncogene Proteins c-fos; Space Perception}, Month = {Jun}, Number = {23}, Pages = {8661-6}, Pmc = {PMC4060653}, pmid = {24912150}, Pst = {ppublish}, Title = {Encoding and storage of spatial information in the retrosplenial cortex}, Volume = {111}, Year = {2014}, url = {papers/Czajkowski_ProcNatlAcadSciUSA2014.pdf}} @article{Quirin:2014, Abstract = {We introduce a scanless optical method to image neuronal activity in three dimensions simultaneously. Using a spatial light modulator and a custom-designed phase mask, we illuminate and collect light simultaneously from different focal planes and perform calcium imaging of neuronal activity in vitro and in vivo. This method, combining structured illumination with volume projection imaging, could be used as a technological platform for brain activity mapping.}, Author = {Quirin, Sean and Jackson, Jesse and Peterka, Darcy S and Yuste, Rafael}, Date-Added = {2018-01-16 23:36:18 +0000}, Date-Modified = {2018-01-16 23:36:30 +0000}, Doi = {10.3389/fncir.2014.00029}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {brain activity map; calcium imaging; spatial-light-modulator; three-dimensional imaging; volume imaging; technique; method}, Mesh = {Animals; Hippocampus; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Mice; Mice, Inbred C57BL; Neurons; Zebrafish}, Pages = {29}, Pmc = {PMC3982072}, pmid = {24772066}, Pst = {epublish}, Title = {Simultaneous imaging of neural activity in three dimensions}, Volume = {8}, Year = {2014}, url = {papers/Quirin_FrontNeuralCircuits2014.pdf}} @article{Freeman:2014, Abstract = {Understanding brain function requires monitoring and interpreting the activity of large networks of neurons during behavior. Advances in recording technology are greatly increasing the size and complexity of neural data. Analyzing such data will pose a fundamental bottleneck for neuroscience. We present a library of analytical tools called Thunder built on the open-source Apache Spark platform for large-scale distributed computing. The library implements a variety of univariate and multivariate analyses with a modular, extendable structure well-suited to interactive exploration and analysis development. We demonstrate how these analyses find structure in large-scale neural data, including whole-brain light-sheet imaging data from fictively behaving larval zebrafish, and two-photon imaging data from behaving mouse. The analyses relate neuronal responses to sensory input and behavior, run in minutes or less and can be used on a private cluster or in the cloud. Our open-source framework thus holds promise for turning brain activity mapping efforts into biological insights.}, Author = {Freeman, Jeremy and Vladimirov, Nikita and Kawashima, Takashi and Mu, Yu and Sofroniew, Nicholas J and Bennett, Davis V and Rosen, Joshua and Yang, Chao-Tsung and Looger, Loren L and Ahrens, Misha B}, Date-Added = {2018-01-16 23:33:51 +0000}, Date-Modified = {2018-01-16 23:34:15 +0000}, Doi = {10.1038/nmeth.3041}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {technique; method; Computational Biology}, Mesh = {Action Potentials; Animals; Brain; Brain Mapping; Computer Simulation; Computing Methodologies; Data Interpretation, Statistical; Database Management Systems; Databases, Factual; Humans; Information Storage and Retrieval; Models, Neurological; Nerve Net; Neurons; Programming Languages; Software}, Month = {Sep}, Number = {9}, Pages = {941-50}, pmid = {25068736}, Pst = {ppublish}, Title = {Mapping brain activity at scale with cluster computing}, Volume = {11}, Year = {2014}, url = {papers/Freeman_NatMethods2014.pdf}} @article{Mez:2017, Abstract = {Importance: Players of American football may be at increased risk of long-term neurological conditions, particularly chronic traumatic encephalopathy (CTE). Objective: To determine the neuropathological and clinical features of deceased football players with CTE. Design, Setting, and Participants: Case series of 202 football players whose brains were donated for research. Neuropathological evaluations and retrospective telephone clinical assessments (including head trauma history) with informants were performed blinded. Online questionnaires ascertained athletic and military history. Exposures: Participation in American football at any level of play. Main Outcomes and Measures: Neuropathological diagnoses of neurodegenerative diseases, including CTE, based on defined diagnostic criteria; CTE neuropathological severity (stages I to IV or dichotomized into mild [stages I and II] and severe [stages III and IV]); informant-reported athletic history and, for players who died in 2014 or later, clinical presentation, including behavior, mood, and cognitive symptoms and dementia. Results: Among 202 deceased former football players (median age at death, 66 years [interquartile range, 47-76 years]), CTE was neuropathologically diagnosed in 177 players (87%; median age at death, 67 years [interquartile range, 52-77 years]; mean years of football participation, 15.1 [SD, 5.2]), including 0 of 2 pre-high school, 3 of 14 high school (21%), 48 of 53 college (91%), 9 of 14 semiprofessional (64%), 7 of 8 Canadian Football League (88%), and 110 of 111 National Football League (99%) players. Neuropathological severity of CTE was distributed across the highest level of play, with all 3 former high school players having mild pathology and the majority of former college (27 [56%]), semiprofessional (5 [56%]), and professional (101 [86%]) players having severe pathology. Among 27 participants with mild CTE pathology, 26 (96%) had behavioral or mood symptoms or both, 23 (85%) had cognitive symptoms, and 9 (33%) had signs of dementia. Among 84 participants with severe CTE pathology, 75 (89%) had behavioral or mood symptoms or both, 80 (95%) had cognitive symptoms, and 71 (85%) had signs of dementia. Conclusions and Relevance: In a convenience sample of deceased football players who donated their brains for research, a high proportion had neuropathological evidence of CTE, suggesting that CTE may be related to prior participation in football.}, Author = {Mez, Jesse and Daneshvar, Daniel H and Kiernan, Patrick T and Abdolmohammadi, Bobak and Alvarez, Victor E and Huber, Bertrand R and Alosco, Michael L and Solomon, Todd M and Nowinski, Christopher J and McHale, Lisa and Cormier, Kerry A and Kubilus, Caroline A and Martin, Brett M and Murphy, Lauren and Baugh, Christine M and Montenigro, Phillip H and Chaisson, Christine E and Tripodis, Yorghos and Kowall, Neil W and Weuve, Jennifer and McClean, Michael D and Cantu, Robert C and Goldstein, Lee E and Katz, Douglas I and Stern, Robert A and Stein, Thor D and McKee, Ann C}, Date-Added = {2018-01-16 23:13:03 +0000}, Date-Modified = {2018-01-16 23:13:03 +0000}, Doi = {10.1001/jama.2017.8334}, Journal = {JAMA}, Journal-Full = {JAMA}, Mesh = {Adult; Aged; Athletes; Athletic Injuries; Brain; Brain Concussion; Cause of Death; Chronic Traumatic Encephalopathy; Cognition Disorders; Football; Humans; Male; Mental Disorders; Middle Aged; Severity of Illness Index; Substance-Related Disorders; United States; tau Proteins}, Month = {07}, Number = {4}, Pages = {360-370}, pmid = {28742910}, Pst = {ppublish}, Title = {Clinicopathological Evaluation of Chronic Traumatic Encephalopathy in Players of American Football}, Volume = {318}, Year = {2017}, url = {papers/Mez_JAMA2017.pdf}} @article{McKee:2014, Abstract = {The benefits of regular exercise, physical fitness and sports participation on cardiovascular and brain health are undeniable. Physical activity reduces the risk for cardiovascular disease, type 2 diabetes, hypertension, obesity, and stroke, and produces beneficial effects on cholesterol levels, antioxidant systems, inflammation, and vascular function. Exercise also enhances psychological health, reduces age-related loss of brain volume, improves cognition, reduces the risk of developing dementia, and impedes neurodegeneration. Nonetheless, the play of sports is associated with risks, including a risk for mild TBI (mTBI) and, rarely, catastrophic traumatic injury and death. There is also growing awareness that repetitive mTBIs, such as concussion and subconcussion, can occasionally produce persistent cognitive, behavioral, and psychiatric problems as well as lead to the development of a neurodegeneration, chronic traumatic encephalopathy (CTE). In this review, we summarize the beneficial aspects of sports participation on psychological, emotional, physical and cognitive health, and specifically analyze some of the less common adverse neuropathological outcomes, including concussion, second-impact syndrome, juvenile head trauma syndrome, catastrophic sudden death, and CTE. CTE is a latent neurodegeneration clinically associated with behavioral changes, executive dysfunction and cognitive impairments, and pathologically characterized by frontal and temporal lobe atrophy, neuronal and axonal loss, and abnormal deposits of paired helical filament (PHF)-tau and 43 kDa TAR deoxyribonucleic acid (DNA)-binding protein (TDP-43). CTE often occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including motor neuron disease (CTE-MND). Although the incidence and prevalence of CTE are not known, CTE has been reported most frequently in American football players and boxers. Other sports associated with CTE include ice hockey, professional wrestling, soccer, rugby, and baseball.}, Author = {McKee, Ann C and Daneshvar, Daniel H and Alvarez, Victor E and Stein, Thor D}, Date-Added = {2018-01-16 23:12:43 +0000}, Date-Modified = {2018-01-16 23:12:43 +0000}, Doi = {10.1007/s00401-013-1230-6}, Journal = {Acta Neuropathol}, Journal-Full = {Acta neuropathologica}, Mesh = {Animals; Athletic Injuries; Brain; Brain Injuries; Cognition; Humans; Sports}, Month = {Jan}, Number = {1}, Pages = {29-51}, Pmc = {PMC4255282}, pmid = {24366527}, Pst = {ppublish}, Title = {The neuropathology of sport}, Volume = {127}, Year = {2014}, url = {papers/McKee_ActaNeuropathol2014.pdf}} @article{Viswanathan:2012, Abstract = {Subplate neurons (SPNs) are a population of neurons in the mammalian cerebral cortex that exist predominantly in the prenatal and early postnatal period. Loss of SPNs prevents the functional maturation of the cerebral cortex. SPNs receive subcortical input from the thalamus and relay this information to the developing cortical plate and thereby can influence cortical activity in a feedforward manner. Little is known about potential feedback projections from the cortical plate to SPNs. Thus, we investigated the spatial distribution of intracortical synaptic inputs to SPNs in vitro in mouse auditory cortex by photostimulation. We find that SPNs fell into two broad classes based on their distinct spatial patterns of synaptic inputs. The first class of SPNs receives inputs from only deep cortical layers, while the second class of SPNs receives inputs from deep as well as superficial layers including layer 4. We find that superficial cortical inputs to SPNs emerge in the second postnatal week and that SPNs that receive superficial cortical input are located more superficially than those that do not. Our data thus suggest that distinct circuits are present in the subplate and that, while SPNs participate in an early feedforward circuit, they are also involved in a feedback circuit at older ages. Together, our results show that SPNs are tightly integrated into the developing thalamocortical and intracortical circuit. The feedback projections from the cortical plate might enable SPNs to amplify thalamic inputs to SPNs.}, Author = {Viswanathan, Sarada and Bandyopadhyay, Sharba and Kao, Joseph P Y and Kanold, Patrick O}, Date-Added = {2018-01-16 23:08:52 +0000}, Date-Modified = {2018-01-16 23:08:52 +0000}, Doi = {10.1523/JNEUROSCI.4748-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Cerebral Cortex; Female; Male; Mice; Mice, Inbred C57BL; Nerve Net; Neural Pathways; Photic Stimulation; Thalamus}, Month = {Feb}, Number = {5}, Pages = {1589-601}, Pmc = {PMC3517995}, pmid = {22302801}, Pst = {ppublish}, Title = {Changing microcircuits in the subplate of the developing cortex}, Volume = {32}, Year = {2012}, url = {papers/Viswanathan_JNeurosci2012.pdf}} @article{Petit:2014, Abstract = {OBJECTIVE: Subcortical band heterotopia (SBH) is a cortical malformation formed when neocortical neurons prematurely stop their migration in the white matter, forming a heterotopic band below the normotopic cortex, and is generally associated with intractable epilepsy. Although it is clear that the band heterotopia and the overlying cortex both contribute to creating an abnormal circuit prone to generate epileptic discharges, it is less understood which part of this circuitry is the most critical. Here, we sought to identify the origin of epileptiform activity in a targeted genetic model of SBH in rats. METHODS: Rats with SBH (Dcx-KD rats) were generated by knocking down the Dcx gene using shRNA vectors transfected into neocortical progenitors of rat embryos. Origin, spatial extent, and laminar profile of bicuculline-induced interictal-like activity on neocortical slices were analyzed by using extracellular recordings from 60-channel microelectrode arrays. Susceptibility to pentylenetetrazole-induced seizures was assessed by electrocorticography in head-restrained nonanesthetized rats. RESULTS: We show that the band heterotopia does not constitute a primary origin for interictal-like epileptiform activity in vitro and is dispensable for generating induced seizures in vivo. Furthermore, we report that most interictal-like discharges originating in the overlying cortex secondarily propagate to the band heterotopia. Importantly, we found that in vivo suppression of neuronal excitability in SBH does not alter the higher propensity of Dcx-KD rats to display seizures. INTERPRETATION: These results suggest a major role of the normotopic cortex over the band heterotopia in generating interictal epileptiform activity and seizures in brains with SBH.}, Author = {Petit, Ludovic Franck and Jalabert, Marion and Buhler, Emmanuelle and Malvache, Arnaud and Peret, Ang{\'e}lique and Chauvin, Yoann and Watrin, Fran{\c c}oise and Represa, Alfonso and Manent, Jean-Bernard}, Date-Added = {2018-01-16 23:03:36 +0000}, Date-Modified = {2018-01-16 23:03:36 +0000}, Doi = {10.1002/ana.24237}, Journal = {Ann Neurol}, Journal-Full = {Annals of neurology}, Mesh = {Animals; Bicuculline; Cerebral Cortex; Classical Lissencephalies and Subcortical Band Heterotopias; Convulsants; Disease Models, Animal; Electroencephalography; Electrophysiological Phenomena; Epilepsy; Gene Knockdown Techniques; Microtubule-Associated Proteins; Neocortex; Nerve Net; Neuropeptides; Pentylenetetrazole; Rats; Rats, Transgenic; Seizures; Somatosensory Cortex}, Month = {Sep}, Number = {3}, Pages = {428-42}, pmid = {25074818}, Pst = {ppublish}, Title = {Normotopic cortex is the major contributor to epilepsy in experimental double cortex}, Volume = {76}, Year = {2014}, url = {papers/Petit_AnnNeurol2014.pdf}} @article{Herculano-Houzel:2014, Abstract = {It is a widespread notion that the proportion of glial to neuronal cells in the brain increases with brain size, to the point that glial cells represent "about 90% of all cells in the human brain." This notion, however, is wrong on both counts: neither does the glia/neuron ratio increase uniformly with brain size, nor do glial cells represent the majority of cells in the human brain. This review examines the origin of interest in the glia/neuron ratio; the original evidence that led to the notion that it increases with brain size; the extent to which this concept can be applied to white matter and whole brains and the recent supporting evidence that the glia/neuron ratio does not increase with brain size, but rather, and in surprisingly uniform fashion, with decreasing neuronal density due to increasing average neuronal cell size, across brain structures and species. Variations in the glia/neuron ratio are proposed to be related not to the supposed larger metabolic cost of larger neurons (given that this cost is not found to vary with neuronal density), but simply to the large variation in neuronal sizes across brain structures and species in the face of less overall variation in glial cell sizes, with interesting implications for brain physiology. The emerging evidence that the glia/neuron ratio varies uniformly across the different brain structures of mammalian species that diverged as early as 90 million years ago in evolution highlights how fundamental for brain function must be the interaction between glial cells and neurons.}, Author = {Herculano-Houzel, Suzana}, Date-Added = {2018-01-16 23:02:14 +0000}, Date-Modified = {2018-01-16 23:02:43 +0000}, Doi = {10.1002/glia.22683}, Journal = {Glia}, Journal-Full = {Glia}, Keywords = {brain metabolism; brain size; cell size; teaching; facts}, Mesh = {Animals; Biological Evolution; Brain; Cell Size; Humans; Neuroglia; Neurons; Organ Size; White Matter}, Month = {Sep}, Number = {9}, Pages = {1377-91}, pmid = {24807023}, Pst = {ppublish}, Title = {The glia/neuron ratio: how it varies uniformly across brain structures and species and what that means for brain physiology and evolution}, Volume = {62}, Year = {2014}, url = {papers/Herculano-Houzel_Glia2014.pdf}} @article{Mori:2013, Abstract = {The orbitofrontal cortex receives multi-modality sensory inputs, including olfactory input, and is thought to be involved in conscious perception of the olfactory image of objects. Generation of olfactory consciousness may require neuronal circuit mechanisms for the "binding" of distributed neuronal activities, with each constituent neuron representing a specific component of an olfactory percept. The shortest neuronal pathway for odor signals to reach the orbitofrontal cortex is olfactory sensory neuron-olfactory bulb-olfactory cortex-orbitofrontal cortex, but other pathways exist, including transthalamic pathways. Here, we review studies on the structural organization and functional properties of the shortest pathway, and propose a model of neuronal circuit mechanisms underlying the temporal bindings of distributed neuronal activities in the olfactory cortex. We describe a hypothesis that suggests functional roles of gamma oscillations in the bindings. This hypothesis proposes that two types of projection neurons in the olfactory bulb, tufted cells and mitral cells, play distinct functional roles in bindings at neuronal circuits in the olfactory cortex: tufted cells provide specificity-projecting circuits which send odor information with early-onset fast gamma synchronization, while mitral cells give rise to dispersedly-projecting feed-forward binding circuits which transmit the response synchronization timing with later-onset slow gamma synchronization. This hypothesis also suggests a sequence of bindings in the olfactory cortex: a small-scale binding by the early-phase fast gamma synchrony of tufted cell inputs followed by a larger-scale binding due to the later-onset slow gamma synchrony of mitral cell inputs. We discuss that behavioral state, including wakefulness and sleep, regulates gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex.}, Author = {Mori, Kensaku and Manabe, Hiroyuki and Narikiyo, Kimiya and Onisawa, Naomi}, Date-Added = {2018-01-16 23:01:59 +0000}, Date-Modified = {2018-01-16 23:01:59 +0000}, Doi = {10.3389/fpsyg.2013.00743}, Journal = {Front Psychol}, Journal-Full = {Frontiers in psychology}, Keywords = {gamma synchronization; olfactory bulb; olfactory consciousness; olfactory cortex; orbitofrontal cortex; tufted and mitral cells}, Pages = {743}, Pmc = {PMC3797617}, pmid = {24137148}, Pst = {epublish}, Title = {Olfactory consciousness and gamma oscillation couplings across the olfactory bulb, olfactory cortex, and orbitofrontal cortex}, Volume = {4}, Year = {2013}, url = {papers/Mori_FrontPsychol2013.pdf}} @article{Goard2016, Abstract = {Mapping specific sensory features to future motor actions is a crucial capability of mammalian nervous systems. We investigated the role of visual (V1), posterior parietal (PPC), and frontal motor (fMC) cortices for sensorimotor mapping in mice during performance of a memory-guided visual discrimination task. Large-scale calcium imaging revealed that V1, PPC, and fMC neurons exhibited heterogeneous responses spanning all task epochs (stimulus, delay, response). Population analyses demonstrated unique encoding of stimulus identity and behavioral choice information across regions, with V1 encoding stimulus, fMC encoding choice even early in the trial, and PPC multiplexing the two variables. Optogenetic inhibition during behavior revealed that all regions were necessary during the stimulus epoch, but only fMC was required during the delay and response epochs. Stimulus identity can thus be rapidly transformed into behavioral choice, requiring V1, PPC, and fMC during the transformation period, but only fMC for maintaining the choice in memory prior to execution.}, Author = {Goard, Michael J and Pho, Gerald N and Woodson, Jonathan and Sur, Mriganka}, Date-Added = {2018-01-16 23:01:32 +0000}, Date-Modified = {2018-01-16 23:01:32 +0000}, Doi = {10.7554/eLife.13764}, Journal = {elife}, Journal-Full = {eLife}, Keywords = {decision making; mouse; multiphoton microscopy; neuroscience; optogenetics; short-term memory}, Mesh = {Animals; Brain Mapping; Choice Behavior; Functional Neuroimaging; Memory; Mice; Optogenetics; Parietal Lobe; Sensorimotor Cortex; Visual Cortex; Visual Perception}, Month = {08}, Pmc = {PMC4974053}, pmid = {27490481}, Pst = {epublish}, Title = {Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions}, Volume = {5}, Year = {2016}, url = {papers/Goard_Elife2016.pdf}} @article{Guo:2015, Abstract = {Mammalian cerebral cortex is accepted as being critical for voluntary motor control, but what functions depend on cortex is still unclear. Here we used rapid, reversible optogenetic inhibition to test the role of cortex during a head-fixed task in which mice reach, grab, and eat a food pellet. Sudden cortical inhibition blocked initiation or froze execution of this skilled prehension behavior, but left untrained forelimb movements unaffected. Unexpectedly, kinematically normal prehension occurred immediately after cortical inhibition, even during rest periods lacking cue and pellet. This 'rebound' prehension was only evoked in trained and food-deprived animals, suggesting that a motivation-gated motor engram sufficient to evoke prehension is activated at inhibition's end. These results demonstrate the necessity and sufficiency of cortical activity for enacting a learned skill.}, Author = {Guo, Jian-Zhong and Graves, Austin R and Guo, Wendy W and Zheng, Jihong and Lee, Allen and Rodr{\'\i}guez-Gonz{\'a}lez, Juan and Li, Nuo and Macklin, John J and Phillips, James W and Mensh, Brett D and Branson, Kristin and Hantman, Adam W}, Date-Added = {2018-01-16 23:00:56 +0000}, Date-Modified = {2018-01-16 23:01:17 +0000}, Doi = {10.7554/eLife.10774}, Journal = {Elife}, Journal-Full = {eLife}, Keywords = {cortex; motor control; mouse; neuroscience; optogenetics; behavior; method; technique}, Mesh = {Animals; Cerebral Cortex; Feeding Behavior; Locomotion; Mice; Optogenetics}, Month = {Dec}, Pages = {e10774}, Pmc = {PMC4749564}, pmid = {26633811}, Pst = {epublish}, Title = {Cortex commands the performance of skilled movement}, Volume = {4}, Year = {2015}, url = {papers/Guo_Elife2015.pdf}} @article{Crair:2016, Abstract = {Although much is known about the regenerative capacity of retinal ganglion cells, very significant barriers remain in our ability to restore visual function following traumatic injury or disease-induced degeneration. Here we summarize our current understanding of the factors regulating axon guidance and target engagement in regenerating axons, and review the state of the field of neural regeneration, focusing on the visual system and highlighting studies using other model systems that can inform analysis of visual system regeneration. This overview is motivated by a Society for Neuroscience Satellite meeting, "Reconnecting Neurons in the Visual System," held in October 2015 sponsored by the National Eye Institute as part of their "Audacious Goals Initiative" and co-organized by Carol Mason (Columbia University) and Michael Crair (Yale University). The collective wisdom of the conference participants pointed to important gaps in our knowledge and barriers to progress in promoting the restoration of visual system function. This article is thus a summary of our existing understanding of visual system regeneration and provides a blueprint for future progress in the field.}, Author = {Crair, Michael C and Mason, Carol A}, Date-Added = {2018-01-16 22:59:41 +0000}, Date-Modified = {2018-01-16 22:59:41 +0000}, Doi = {10.1523/JNEUROSCI.1711-16.2016}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {axon; axon guidance; axon regeneration; eye; lateral geniculate nucleus; optic nerve; regeneration; retina; retinal ganglion cells; superior colliculus; traumatic brain injury; vision; visual cortex}, Mesh = {Animals; Axons; Brain; Humans; Ocular Physiological Phenomena; Optic Nerve; Retinal Ganglion Cells; Visual Pathways}, Month = {Oct}, Number = {42}, Pages = {10707-10722}, Pmc = {PMC5083002}, pmid = {27798125}, Pst = {ppublish}, Title = {Reconnecting Eye to Brain}, Volume = {36}, Year = {2016}, url = {papers/Crair_JNeurosci2016.pdf}} @article{Seybold:2015, Abstract = {Cortical function is regulated by a strikingly diverse array of local-circuit inhibitory neurons. We evaluated how optogenetically activating somatostatin- and parvalbumin-positive interneurons subtractively or divisively suppressed auditory cortical cells' responses to tones. In both awake and anesthetized animals, we found that activating either family of interneurons produced mixtures of divisive and subtractive effects and that simultaneously recorded neurons were often suppressed in qualitatively different ways. A simple network model shows that threshold nonlinearities can interact with network activity to transform subtractive inhibition of neurons into divisive inhibition of networks, or vice versa. Varying threshold and the strength of suppression of a model neuron could determine whether the effect of inhibition appeared divisive, subtractive, or both. We conclude that the characteristics of response inhibition specific to a single interneuron type can be "masked" by the network configuration and cellular properties of the network in which they are embedded.}, Author = {Seybold, Bryan A and Phillips, Elizabeth A K and Schreiner, Christoph E and Hasenstaub, Andrea R}, Date-Added = {2018-01-16 22:58:49 +0000}, Date-Modified = {2018-01-16 22:58:49 +0000}, Doi = {10.1016/j.neuron.2015.09.013}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Auditory Cortex; Interneurons; Mice; Mice, Transgenic; Nerve Net; Neural Inhibition; Optogenetics}, Month = {Sep}, Number = {6}, Pages = {1181-1192}, Pmc = {PMC4635400}, pmid = {26402602}, Pst = {ppublish}, Title = {Inhibitory Actions Unified by Network Integration}, Volume = {87}, Year = {2015}, url = {papers/Seybold_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.09.013}} @article{Ledochowitsch:2015, Abstract = {BACKGROUND: To dissect the intricate workings of neural circuits, it is essential to gain precise control over subsets of neurons while retaining the ability to monitor larger-scale circuit dynamics. This requires the ability to both evoke and record neural activity simultaneously with high spatial and temporal resolution. NEW METHOD: In this paper we present approaches that address this need by combining micro-electrocorticography (μECoG) with optogenetics in ways that avoid photovoltaic artifacts. RESULTS: We demonstrate that variations of this approach are broadly applicable across three commonly studied mammalian species - mouse, rat, and macaque monkey - and that the recorded μECoG signal shows complex spectral and spatio-temporal patterns in response to optical stimulation. COMPARISON WITH EXISTING METHODS: While optogenetics provides the ability to excite or inhibit neural subpopulations in a targeted fashion, large-scale recording of resulting neural activity remains challenging. Recent advances in optical physiology, such as genetically encoded Ca(2+) indicators, are promising but currently do not allow simultaneous recordings from extended cortical areas due to limitations in optical imaging hardware. CONCLUSIONS: We demonstrate techniques for the large-scale simultaneous interrogation of cortical circuits in three commonly used mammalian species.}, Author = {Ledochowitsch, P and Yazdan-Shahmorad, A and Bouchard, K E and Diaz-Botia, C and Hanson, T L and He, J-W and Seybold, B A and Olivero, E and Phillips, E A K and Blanche, T J and Schreiner, C E and Hasenstaub, A and Chang, E F and Sabes, P N and Maharbiz, M M}, Date-Added = {2018-01-16 22:56:30 +0000}, Date-Modified = {2018-01-16 22:56:50 +0000}, Doi = {10.1016/j.jneumeth.2015.07.028}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {Auditory; Cranial window; ECoG; Epidural; Mouse; NHP; Optogenetics; Parvalbumin; Rat; technique}, Mesh = {Animals; Artifacts; Auditory Perception; Cerebral Cortex; Computer-Aided Design; Electric Impedance; Electrocorticography; Electrodes, Implanted; Equipment Design; Evoked Potentials; Macaca mulatta; Male; Mice, Transgenic; Neural Inhibition; Neurons; Optogenetics; Photic Stimulation; Rats, Long-Evans; Tin Compounds}, Month = {Dec}, Pages = {220-31}, pmid = {26296286}, Pst = {ppublish}, Title = {Strategies for optical control and simultaneous electrical readout of extended cortical circuits}, Volume = {256}, Year = {2015}, url = {papers/Ledochowitsch_JNeurosciMethods2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2015.07.028}} @article{Ryan:2017, Abstract = {Many states have recently made significant changes to their legislation making recreational and/or medical marijuana use by adults legal. Although these laws, for the most part, have not targeted the adolescent population, they have created an environment in which marijuana increasingly is seen as acceptable, safe, and therapeutic. This clinical report offers guidance to the practicing pediatrician based on existing evidence and expert opinion/consensus of the American Academy of Pediatrics regarding anticipatory guidance and counseling to teenagers and their parents about marijuana and its use. The recently published technical report provides the detailed evidence and references regarding the research on which the information in this clinical report is based.}, Author = {Ryan, Sheryl A and Ammerman, Seth D and {COMMITTEE ON SUBSTANCE USE AND PREVENTION}}, Date-Added = {2018-01-16 22:55:01 +0000}, Date-Modified = {2018-01-16 22:55:01 +0000}, Doi = {10.1542/peds.2016-4069}, Journal = {Pediatrics}, Journal-Full = {Pediatrics}, Mesh = {Adolescent; Counseling; Humans; Marijuana Abuse; Marijuana Smoking; Parents; Pediatricians; Physician's Role}, Month = {Mar}, Number = {3}, pmid = {28242859}, Pst = {ppublish}, Title = {Counseling Parents and Teens About Marijuana Use in the Era of Legalization of Marijuana}, Volume = {139}, Year = {2017}, url = {papers/Ryan_Pediatrics2017.pdf}} @article{Tohmi:2009, Abstract = {Endogenous fluorescence signals derived from mitochondria reflect activity-dependent changes in brain metabolism and may be exploited in functional brain imaging. Endogenous flavoprotein fluorescence imaging in mice is especially important because many genetically manipulated strains of mice are available and the transparent skull of mice allows transcranial fluorescence imaging of cortical activities. In the primary sensory areas of mice, cortical activities and experience-dependent plasticity have been investigated using transcranial fluorescence imaging. Furthermore, differential imaging, based on stimulus specificity of cortical areas, distinguished activities in higher visual areas around the primary visual cortex from those in primary visual cortex. The combination of transcranial fluorescence imaging with the suppression of cortical activities using photobleaching of flavoproteins is expected to aid in elucidating the roles of sensory cortices including higher areas in mice.}, Author = {Tohmi, Manavu and Takahashi, Kuniyuki and Kubota, Yamato and Hishida, Ryuichi and Shibuki, Katsuei}, Date-Added = {2018-01-16 22:53:43 +0000}, Date-Modified = {2018-01-16 22:54:17 +0000}, Doi = {10.1111/j.1471-4159.2009.05926.x}, Journal = {J Neurochem}, Journal-Full = {Journal of neurochemistry}, Keywords = {optical physiology; imaging; intrinsic signal; function; map}, Mesh = {Animals; Cerebral Cortex; Flavoproteins; Mice; Neuronal Plasticity; Photobleaching; Spectrometry, Fluorescence}, Month = {May}, Pages = {3-9}, pmid = {19393002}, Pst = {ppublish}, Title = {Transcranial flavoprotein fluorescence imaging of mouse cortical activity and plasticity}, Volume = {109 Suppl 1}, Year = {2009}, url = {papers/Tohmi_JNeurochem2009.pdf}} @article{Kondo:2016, Abstract = {A minicolumn is the smallest anatomical module in the cortical architecture, but it is still in debate whether it serves as functional units for cortical processing. In the rodent primary visual cortex (V1), neurons with different preferred orientations are mixed horizontally in a salt and pepper manner, but vertical functional organization was not examined. In this study, we found that neurons with similar orientation preference are weakly but significantly clustered vertically in a short length and horizontally in the scale of a minicolumn. Interestingly, the vertical clustering is found only in a part of minicolumns, and others are composed of neurons with a variety of orientation preferences. Thus, the mouse V1 is a mixture of vertical clusters of neurons with various degrees of orientation similarity, which may be the compromise between the brain size and keeping the vertical clusters of similarly tuned neurons at least in a subset of clusters.}, Author = {Kondo, Satoru and Yoshida, Takashi and Ohki, Kenichi}, Date-Added = {2018-01-16 22:52:09 +0000}, Date-Modified = {2018-01-16 22:52:09 +0000}, Doi = {10.1038/ncomms13210}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Month = {Oct}, Pages = {13210}, Pmc = {PMC5078743}, pmid = {27767032}, Pst = {epublish}, Title = {Mixed functional microarchitectures for orientation selectivity in the mouse primary visual cortex}, Volume = {7}, Year = {2016}, url = {papers/Kondo_NatCommun2016.pdf}} @article{Kirmse:2015, Abstract = {A large body of evidence from in vitro studies suggests that GABA is depolarizing during early postnatal development. However, the mode of GABA action in the intact developing brain is unknown. Here we examine the in vivo effects of GABA in cells of the upper cortical plate using a combination of electrophysiological and Ca(2+)-imaging techniques. We report that at postnatal days (P) 3-4, GABA depolarizes the majority of immature neurons in the occipital cortex of anaesthetized mice. At the same time, GABA does not efficiently activate voltage-gated Ca(2+) channels and fails to induce action potential firing. Blocking GABA(A) receptors disinhibits spontaneous network activity, whereas allosteric activation of GABA(A) receptors has the opposite effect. In summary, our data provide evidence that in vivo GABA acts as a depolarizing neurotransmitter imposing an inhibitory control on network activity in the neonatal (P3-4) neocortex.}, Author = {Kirmse, Knut and Kummer, Michael and Kovalchuk, Yury and Witte, Otto W and Garaschuk, Olga and Holthoff, Knut}, Date-Added = {2018-01-16 22:50:06 +0000}, Date-Modified = {2018-01-16 22:50:06 +0000}, Doi = {10.1038/ncomms8750}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Mesh = {Action Potentials; Animals; Animals, Newborn; GABA Agents; Mice; Neocortex; Nerve Net; Neural Inhibition; Neurons; Occipital Lobe; Patch-Clamp Techniques; Receptors, GABA-A; Synaptic Transmission; gamma-Aminobutyric Acid}, Month = {Jul}, Pages = {7750}, pmid = {26177896}, Pst = {epublish}, Title = {GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo}, Volume = {6}, Year = {2015}, url = {papers/Kirmse_NatCommun2015.pdf}} @article{Minocha:2015, Abstract = {Guidepost cells present at and surrounding the midline provide guidance cues that orient the growing axons through commissures. Here we show that the transcription factor Nkx2.1 known to control the specification of GABAergic interneurons also regulates the differentiation of astroglia and polydendrocytes within the mouse anterior commissure (AC). Nkx2.1-positive glia were found to originate from three germinal regions of the ventral telencephalon. Nkx2.1-derived glia were observed in and around the AC region by E14.5. Thereafter, a selective cell ablation strategy showed a synergistic role of Nkx2.1-derived cells, both GABAergic interneurons and astroglia, towards the proper formation of the AC. Finally, our results reveal that the Nkx2.1-regulated cells mediate AC axon guidance through the expression of the repellent cue, Slit2. These results bring forth interesting insights about the spatial and temporal origin of midline telencephalic glia, and highlight the importance of neurons and astroglia towards the formation of midline commissures.}, Author = {Minocha, Shilpi and Valloton, Delphine and Ypsilanti, Athena R and Fiumelli, Hubert and Allen, Elizabeth A and Yanagawa, Yuchio and Marin, Oscar and Ch{\'e}dotal, Alain and Hornung, Jean-Pierre and Lebrand, C{\'e}cile}, Date-Added = {2018-01-16 22:49:01 +0000}, Date-Modified = {2018-01-16 22:49:01 +0000}, Doi = {10.1038/ncomms7887}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Mesh = {Animals; Anterior Cerebellar Commissure; Astrocytes; Axons; Cell Movement; Electroporation; Embryo, Mammalian; GABAergic Neurons; Gene Expression Regulation, Developmental; Immunohistochemistry; In Vitro Techniques; Intercellular Signaling Peptides and Proteins; Interneurons; Mice; Nerve Tissue Proteins; Neuroglia; Neurons; Nuclear Proteins; Telencephalon; Thyroid Nuclear Factor 1; Transcription Factors}, Month = {Apr}, Pages = {6887}, Pmc = {PMC4423212}, pmid = {25904499}, Pst = {epublish}, Title = {Nkx2.1-derived astrocytes and neurons together with Slit2 are indispensable for anterior commissure formation}, Volume = {6}, Year = {2015}, url = {papers/Minocha_NatCommun2015.pdf}} @article{Srivatsa:2014, Abstract = {The pyramidal neurons of the mammalian neocortex form two major types of long-range connections-corticocortical and cortico-subcortical. The transcription factors Satb2 and Ctip2 are critical regulators of neuronal cell fate that control interhemispheric versus corticofugal connections respectively. Here, we investigate the axon guidance molecules downstream of Satb2 and Ctip2 that establish these connections. We show that the expression of two Netrin1 receptors- DCC and Unc5C is under direct negative regulation by Satb2 and Ctip2, respectively. Further, we show that the Netrin1-Unc5C/DCC interaction is involved in controlling the interhemispherical projection in a subset of early born, deep layer callosal neurons.}, Author = {Srivatsa, Swathi and Parthasarathy, Srinivas and Britanova, Olga and Bormuth, Ingo and Donahoo, Amber-Lee and Ackerman, Susan L and Richards, Linda J and Tarabykin, Victor}, Date-Added = {2018-01-16 22:48:47 +0000}, Date-Modified = {2018-01-16 22:48:47 +0000}, Doi = {10.1038/ncomms4708}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Mesh = {Animals; Chromatin Immunoprecipitation; Corpus Callosum; DCC Receptor; DNA Primers; Electroporation; Gene Expression Regulation, Developmental; In Situ Hybridization; Luciferases; Mice; Morphogenesis; Netrin Receptors; Plasmids; Receptors, Cell Surface; Receptors, Nerve Growth Factor; Tumor Suppressor Proteins}, Month = {Apr}, Pages = {3708}, Pmc = {PMC3997811}, pmid = {24739528}, Pst = {epublish}, Title = {Unc5C and DCC act downstream of Ctip2 and Satb2 and contribute to corpus callosum formation}, Volume = {5}, Year = {2014}, url = {papers/Srivatsa_NatCommun2014.pdf}} @article{Hazrati:2013, Abstract = {BACKGROUND: Chronic traumatic encephalopathy (CTE) is the term coined for the neurodegenerative disease often suspected in athletes with histories of repeated concussion and progressive dementia. Histologically, CTE is defined as a tauopathy with a distribution of tau-positive neurofibrillary tangles (NFTs) that is distinct from other tauopathies, and usually shows an absence of beta-amyloid deposits, in contrast to Alzheimer's disease (AD). Although the connection between repeated concussions and CTE-type neurodegeneration has been recently proposed, this causal relationship has not yet been firmly established. Also, the prevalence of CTE among athletes with multiple concussions is unknown. METHODS: We performed a consecutive case series brain autopsy study on six retired professional football players from the Canadian Football League (CFL) with histories of multiple concussions and significant neurological decline. RESULTS: All participants had progressive neurocognitive decline prior to death; however, only 3 cases had post-mortem neuropathological findings consistent with CTE. The other 3 participants had pathological diagnoses of AD, amyotrophic lateral sclerosis (ALS), and Parkinson's disease (PD). Moreover, the CTE cases showed co-morbid pathology of cancer, vascular disease, and AD. DISCUSSION: Our case studies highlight that not all athletes with history of repeated concussions and neurological symptomology present neuropathological changes of CTE. These preliminary findings support the need for further research into the link between concussion and CTE as well as the need to expand the research to other possible causes of taupathy in athletes. They point to a critical need for prospective studies with good sampling methods to allow us to understand the relationship between multiple concussions and the development of CTE.}, Author = {Hazrati, Lili-Naz and Tartaglia, Maria C and Diamandis, Phedias and Davis, Karen D and Green, Robin E and Wennberg, Richard and Wong, Janice C and Ezerins, Leo and Tator, Charles H}, Date-Added = {2018-01-16 22:47:35 +0000}, Date-Modified = {2018-01-16 22:47:35 +0000}, Doi = {10.3389/fnhum.2013.00222}, Journal = {Front Hum Neurosci}, Journal-Full = {Frontiers in human neuroscience}, Keywords = {chronic traumatic encephalopathy; dementia; neurodegenerative disease; professional athletes; repetitive brain injury}, Pages = {222}, Pmc = {PMC3662898}, pmid = {23745112}, Pst = {epublish}, Title = {Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology}, Volume = {7}, Year = {2013}, url = {papers/Hazrati_FrontHumNeurosci2013.pdf}} @article{Zhuang:2017, Abstract = {Visual perception and behavior are mediated by cortical areas that have been distinguished using architectonic and retinotopic criteria. We employed fluorescence imaging and GCaMP6 reporter mice to generate retinotopic maps, revealing additional regions of retinotopic organization that extend into barrel and retrosplenial cortices. Aligning retinotopic maps to architectonic borders, we found a mismatch in border location, indicating that architectonic borders are not aligned with the retinotopic transition at the vertical meridian. We also assessed the representation of visual space within each region, finding that four visual areas bordering V1 (LM, P, PM and RL) display complementary representations, with overlap primarily at the central hemifield. Our results extend our understanding of the organization of mouse cortex to include up to 16 distinct retinotopically organized regions.}, Author = {Zhuang, Jun and Ng, Lydia and Williams, Derric and Valley, Matthew and Li, Yang and Garrett, Marina and Waters, Jack}, Date-Added = {2018-01-16 22:40:48 +0000}, Date-Modified = {2018-01-16 22:40:48 +0000}, Doi = {10.7554/eLife.18372}, Journal = {Elife}, Journal-Full = {eLife}, Keywords = {cortex; mouse; neuroscience; topographic map; visual map}, Month = {Jan}, Pmc = {PMC5218535}, pmid = {28059700}, Pst = {epublish}, Title = {An extended retinotopic map of mouse cortex}, Volume = {6}, Year = {2017}, url = {papers/Zhuang_Elife2017.pdf}} @article{Sulak:2016, Abstract = {A major constraint on the evolution of large body sizes in animals is an increased risk of developing cancer. There is no correlation, however, between body size and cancer risk. This lack of correlation is often referred to as 'Peto's Paradox'. Here, we show that the elephant genome encodes 20 copies of the tumor suppressor gene TP53 and that the increase in TP53 copy number occurred coincident with the evolution of large body sizes, the evolution of extreme sensitivity to genotoxic stress, and a hyperactive TP53 signaling pathway in the elephant (Proboscidean) lineage. Furthermore, we show that several of the TP53 retrogenes (TP53RTGs) are transcribed and likely translated. While TP53RTGs do not appear to directly function as transcription factors, they do contribute to the enhanced sensitivity of elephant cells to DNA damage and the induction of apoptosis by regulating activity of the TP53 signaling pathway. These results suggest that an increase in the copy number of TP53 may have played a direct role in the evolution of very large body sizes and the resolution of Peto's paradox in Proboscideans.}, Author = {Sulak, Michael and Fong, Lindsey and Mika, Katelyn and Chigurupati, Sravanthi and Yon, Lisa and Mongan, Nigel P and Emes, Richard D and Lynch, Vincent J}, Date-Added = {2018-01-16 22:40:23 +0000}, Date-Modified = {2018-01-16 22:40:23 +0000}, Doi = {10.7554/eLife.11994}, Journal = {Elife}, Journal-Full = {eLife}, Keywords = {African elephant; Asian elephant; aardvark; armadillo; cell biology; evolutionary biology; genomics; hyrax}, Mesh = {Animals; Apoptosis; Body Size; DNA Repair; Elephants; Evolution, Molecular; Gene Dosage; Gene Expression Profiling; Genes, p53; Protein Biosynthesis; Signal Transduction; Transcription, Genetic}, Month = {09}, Pmc = {PMC5061548}, pmid = {27642012}, Pst = {epublish}, Title = {TP53 copy number expansion is associated with the evolution of increased body size and an enhanced DNA damage response in elephants}, Volume = {5}, Year = {2016}, url = {papers/Sulak_Elife2016.pdf}} @article{Iverson:2004, Abstract = {PRIMARY OBJECTIVE: To examine the possibility that athletes with multiple concussions show cumulative effects of injury. METHODS AND PROCEDURES: Amateur athletes with a history of three or more concussions were carefully matched (gender, age, education and sport) with athletes with no prior concussions. All completed a computerized neuropsychological test battery at preseason (ImPACT) and then within 5 days of sustaining a concussion (mean = 1.7 days). MAIN OUTCOMES AND RESULTS: There were differences between groups in symptom reporting and memory performance. At baseline (i.e. preseason), athletes with multiple concussions reported more symptoms than athletes with no history of concussion. At approximately 2 days post-injury, athletes with multiple concussions scored significantly lower on memory testing than athletes with a single concussion. Athletes with multiple concussions were 7.7 times more likely to demonstrate a major drop in memory perfomance than athletes with no previous concussions. CONCLUSIONS: This study provides preliminary evidence to suggest that athletes with multiple concussions might have cumulative effects.}, Author = {Iverson, Grant L and Gaetz, Michael and Lovell, Mark R and Collins, Michael W}, Date-Added = {2018-01-16 22:39:33 +0000}, Date-Modified = {2018-01-16 22:39:33 +0000}, Doi = {10.1080/02699050310001617352}, Journal = {Brain Inj}, Journal-Full = {Brain injury}, Mesh = {Adolescent; Amnesia; Analysis of Variance; Athletic Injuries; Brain Concussion; Cumulative Trauma Disorders; Humans; Male; Memory; Neuropsychological Tests; Post-Concussion Syndrome; Psychomotor Performance; Reaction Time}, Month = {May}, Number = {5}, Pages = {433-43}, pmid = {15195792}, Pst = {ppublish}, Title = {Cumulative effects of concussion in amateur athletes}, Volume = {18}, Year = {2004}, url = {papers/Iverson_BrainInj2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/02699050310001617352}} @article{Bogaert:2018, Abstract = {We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development-protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)-were developed. Plasma from mothers of sons, about half of whom had a gay son, along with additional controls (women with no sons, men) was analyzed for male protein-specific antibodies. Results indicated women had significantly higher anti-NLGN4Y levels than men. In addition, after statistically controlling for number of pregnancies, mothers of gay sons, particularly those with older brothers, had significantly higher anti-NLGN4Y levels than did the control samples of women, including mothers of heterosexual sons. The results suggest an association between a maternal immune response to NLGN4Y and subsequent sexual orientation in male offspring.}, Author = {Bogaert, Anthony F and Skorska, Malvina N and Wang, Chao and Gabrie, Jos{\'e} and MacNeil, Adam J and Hoffarth, Mark R and VanderLaan, Doug P and Zucker, Kenneth J and Blanchard, Ray}, Date-Added = {2018-01-16 22:37:59 +0000}, Date-Modified = {2018-01-16 22:37:59 +0000}, Doi = {10.1073/pnas.1705895114}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {NLGN4Y; fraternal birth order; homosexuality; maternal immune hypothesis; sexual orientation}, Month = {Jan}, Number = {2}, Pages = {302-306}, pmid = {29229842}, Pst = {ppublish}, Title = {Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y}, Volume = {115}, Year = {2018}, url = {papers/Bogaert_ProcNatlAcadSciUSA2018.pdf}} @article{Helfrich:2018, Abstract = {The coupled interaction between slow-wave oscillations and sleep spindles during non-rapid-eye-movement (NREM) sleep has been proposed to support memory consolidation. However, little evidence in humans supports this theory. Moreover, whether such dynamic coupling is impaired as a consequence of brain aging in later life, contributing to cognitive and memory decline, is unknown. Combining electroencephalography (EEG), structural MRI, and sleep-dependent memory assessment, we addressed these questions in cognitively normal young and older adults. Directional cross-frequency coupling analyses demonstrated that the slow wave governs a precise temporal coordination of sleep spindles, the quality of which predicts overnight memory retention. Moreover, selective atrophy within the medial frontal cortex in older adults predicted a temporal dispersion of this slow wave-spindle coupling, impairing overnight memory consolidation and leading to forgetting. Prefrontal-dependent deficits in the spatiotemporal coordination of NREM sleep oscillations therefore represent one pathway explaining age-related memory decline.}, Author = {Helfrich, Randolph F and Mander, Bryce A and Jagust, William J and Knight, Robert T and Walker, Matthew P}, Date-Added = {2018-01-16 22:37:20 +0000}, Date-Modified = {2018-01-16 22:37:40 +0000}, Doi = {10.1016/j.neuron.2017.11.020}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {age-related memory decline; aging; atrophy; directional cross-frequency coupling; hierarchical nesting; hippocampus-dependent memory consolidation; overnight forgetting; prefrontal cortex; sleep spindles; slow oscillation; oscillations; synchrony}, Month = {Jan}, Number = {1}, Pages = {221-230.e4}, Pmc = {PMC5754239}, pmid = {29249289}, Pst = {ppublish}, Title = {Old Brains Come Uncoupled in Sleep: Slow Wave-Spindle Synchrony, Brain Atrophy, and Forgetting}, Volume = {97}, Year = {2018}, url = {papers/Helfrich_Neuron2018.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2017.11.020}} @article{Peixoto:2016, Abstract = {Some autistic individuals exhibit abnormal development of the caudate nucleus and associative cortical areas, suggesting potential dysfunction of cortico-basal ganglia (BG) circuits. Using optogenetic and electrophysiological approaches in mice, we identified a narrow postnatal period that is characterized by extensive glutamatergic synaptogenesis in striatal spiny projection neurons (SPNs) and a concomitant increase in corticostriatal circuit activity. SPNs during early development have high intrinsic excitability and respond strongly to cortical afferents despite sparse excitatory inputs. As a result, striatum and corticostriatal connectivity are highly sensitive to acute and chronic changes in cortical activity, suggesting that early imbalances in cortical function alter BG development. Indeed, a mouse model of autism with deletions in Shank3 (Shank3B(-/-)) shows early cortical hyperactivity, which triggers increased SPN excitatory synapse and corticostriatal hyperconnectivity. These results indicate that there is a tight functional coupling between cortex and striatum during early postnatal development and suggest a potential common circuit dysfunction that is caused by cortical hyperactivity.}, Author = {Peixoto, Rui T and Wang, Wengang and Croney, Donyell M and Kozorovitskiy, Yevgenia and Sabatini, Bernardo L}, Date-Added = {2018-01-16 22:36:20 +0000}, Date-Modified = {2018-01-16 22:36:20 +0000}, Doi = {10.1038/nn.4260}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Action Potentials; Animals; Autistic Disorder; Cerebral Cortex; Corpus Striatum; Disease Models, Animal; Female; Male; Mice; Mice, Knockout; Mice, Transgenic; Nerve Tissue Proteins; Neural Pathways; Neurons; Synapses}, Month = {05}, Number = {5}, Pages = {716-724}, Pmc = {PMC4846490}, pmid = {26928064}, Pst = {ppublish}, Title = {Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B(-/-) mice}, Volume = {19}, Year = {2016}, url = {papers/Peixoto_NatNeurosci2016.pdf}} @article{Hikosaka:2010, Abstract = {Surviving in a world with hidden rewards and dangers requires choosing the appropriate behaviours. Recent discoveries indicate that the habenula plays a prominent part in such behavioural choice through its effects on neuromodulator systems, in particular the dopamine and serotonin systems. By inhibiting dopamine-releasing neurons, habenula activation leads to the suppression of motor behaviour when an animal fails to obtain a reward or anticipates an aversive outcome. Moreover, the habenula is involved in behavioural responses to pain, stress, anxiety, sleep and reward, and its dysfunction is associated with depression, schizophrenia and drug-induced psychosis. As a highly conserved structure in the brain, the habenula provides a fundamental mechanism for both survival and decision-making.}, Author = {Hikosaka, Okihide}, Date-Added = {2018-01-16 22:35:23 +0000}, Date-Modified = {2018-01-16 22:35:23 +0000}, Doi = {10.1038/nrn2866}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Avoidance Learning; Decision Making; Habenula; Humans; Mental Disorders; Stress, Psychological}, Month = {Jul}, Number = {7}, Pages = {503-13}, Pmc = {PMC3447364}, pmid = {20559337}, Pst = {ppublish}, Title = {The habenula: from stress evasion to value-based decision-making}, Volume = {11}, Year = {2010}, url = {papers/Hikosaka_NatRevNeurosci2010.pdf}} @article{Zakharenko:1999a, Abstract = {In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell.}, Author = {Zakharenko, S and Chang, S and O'Donoghue, M and Popov, S V}, Date-Added = {2018-01-16 22:35:04 +0000}, Date-Modified = {2018-01-16 22:35:04 +0000}, Journal = {J Cell Biol}, Journal-Full = {The Journal of cell biology}, Mesh = {ADP-Ribosylation Factors; Acetylcholine; Adaptor Protein Complex alpha Subunits; Adaptor Proteins, Vesicular Transport; Animals; Axons; Calcium; Cells, Cultured; Dynamins; Exocytosis; GTP Phosphohydrolases; GTP-Binding Proteins; Membrane Proteins; Nerve Endings; Nerve Tissue Proteins; Neurites; Neuronal Plasticity; Neurons; Neurotransmitter Agents; Presynaptic Terminals; Spider Venoms; Synaptic Vesicles; Xenopus}, Month = {Feb}, Number = {3}, Pages = {507-18}, Pmc = {PMC2132923}, pmid = {9971745}, Pst = {ppublish}, Title = {Neurotransmitter secretion along growing nerve processes: comparison with synaptic vesicle exocytosis}, Volume = {144}, Year = {1999}} @article{Larsen:2006, Abstract = {In the developing neocortex, pyramidal neurons use molecular cues to form axonal arbors selectively in the correct layers. Despite the utility of mice for molecular and genetic studies, little work has been done on the development of layer-specific axonal arborizations of pyramidal neurons in mice. We intracellularly labeled and reconstructed the axons of layer 2/3 and layer 5 pyramidal neurons in slices of primary somatosensory cortex from C57Bl6 mice on postnatal days 7-21. For all neurons studied, the development of the axonal arborizations in mice follows a pattern similar to that seen in other species; laminar specificity of the earliest axonal branches is similar to that of mature animals. At P7, pyramidal neurons are very simple, having only a main descending axon and few primary branches. Between P7 and P10, there is a large increase in the total number of axonal branches, and axons continue to increase in complexity and total length from P10 to P21. Unlike observations in ferrets, cats, and monkeys, two types of layer 2/3 pyramidal neurons are present in both mature and developing mice; cells in superficial layer 2/3 lack axonal arbors in layer 4, and cells close to the layer 4 border have substantial axonal arbors within layer 4. We also describe axonal and dendritic arborization patterns of three pyramidal cell types in layer 5. The axons of tall-tufted layer 5 pyramidal neurons arborize almost exclusively within deep layers while tall-simple, and short layer 5 pyramidal neurons also project axons to superficial layers.}, Author = {Larsen, DeLaine D and Callaway, Edward M}, Date-Added = {2018-01-16 22:34:30 +0000}, Date-Modified = {2018-01-16 22:34:30 +0000}, Doi = {10.1002/cne.20754}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Axons; Dendrites; Imaging, Three-Dimensional; Mice; Mice, Inbred C57BL; Neurons; Pyramidal Cells; Somatosensory Cortex}, Month = {Jan}, Number = {3}, Pages = {398-414}, Pmc = {PMC4651208}, pmid = {16320250}, Pst = {ppublish}, Title = {Development of layer-specific axonal arborizations in mouse primary somatosensory cortex}, Volume = {494}, Year = {2006}, url = {papers/Larsen_JCompNeurol2006.pdf}} @article{Zakharenko:1999, Abstract = {In mature neurons, synaptic vesicles continuously recycle within the presynaptic nerve terminal. In developing axons which are free of contact with a postsynaptic target, constitutive membrane recycling is not localized to the nerve terminal; instead, plasma membrane components undergo cycles of exoendocytosis throughout the whole axonal surface (Matteoli et al., 1992; Kraszewski et al., 1995). Moreover, in growing Xenopus spinal cord neurons in culture, acetylcholine (ACh) is spontaneously secreted in the quantal fashion along the axonal shaft (Evers et al., 1989; Antonov et al., 1998). Here we demonstrate that in Xenopus neurons ACh secretion is mediated by vesicles which recycle locally within the axon. Similar to neurotransmitter release at the presynaptic nerve terminal, ACh secretion along the axon could be elicited by the action potential or by hypertonic solutions. We found that the parameters of neurotransmitter secretion at the nerve terminal and at the middle axon were strikingly similar. These results lead us to conclude that, as in the case of the presynaptic nerve terminal, synaptic vesicles involved in neurotransmitter release along the axon contain a complement of proteins for vesicle docking and Ca2+-dependent fusion. Taken together, our results support the idea that, in developing axons, the rudimentary machinery for quantal neurotransmitter secretion is distributed throughout the whole axonal surface. Maturation of this machinery in the process of synaptic development would improve the fidelity of synaptic transmission during high-frequency stimulation of the presynaptic cell.}, Author = {Zakharenko, S and Chang, S and O'Donoghue, M and Popov, S V}, Date-Added = {2018-01-16 22:34:02 +0000}, Date-Modified = {2018-01-16 22:34:02 +0000}, Journal = {J Cell Biol}, Journal-Full = {The Journal of cell biology}, Mesh = {ADP-Ribosylation Factors; Acetylcholine; Adaptor Protein Complex alpha Subunits; Adaptor Proteins, Vesicular Transport; Animals; Axons; Calcium; Cells, Cultured; Dynamins; Exocytosis; GTP Phosphohydrolases; GTP-Binding Proteins; Membrane Proteins; Nerve Endings; Nerve Tissue Proteins; Neurites; Neuronal Plasticity; Neurons; Neurotransmitter Agents; Presynaptic Terminals; Spider Venoms; Synaptic Vesicles; Xenopus}, Month = {Feb}, Number = {3}, Pages = {507-18}, Pmc = {PMC2132923}, pmid = {9971745}, Pst = {ppublish}, Title = {Neurotransmitter secretion along growing nerve processes: comparison with synaptic vesicle exocytosis}, Volume = {144}, Year = {1999}, url = {papers/Zakharenko_JCellBiol1999.pdf}} @article{Assimacopoulos:2012, Abstract = {The concept of an "organizer" is basic to embryology. An organizer is a portion of the embryo producing signals that lead to the creation of a patterned mature structure from an embryonic primordium. Fibroblast growth factor 8 (FGF8) is a morphogen that disperses from a rostromedial source in the neocortical primordium (NP), forms a rostral-to-caudal (R/C) gradient, and regulates embryonic and neonatal R/C patterns of gene expression in neocortex. Whether FGF8 also has organizer activity that generates the postnatal neocortical area map is uncertain. To test this possibility, new sources of FGF8 were introduced into the mouse NP with in utero microelectroporation at embryonic day 10.5, close to the estimated peak of area patterning. Results differed depending on the position of ectopic FGF8. Ectopic FGF8 in the caudalmost NP could duplicate somatosensory cortex (S1) and primary visual cortex (V1). FGF8 delivered to the midlateral NP generated a sulcus separating rostral and caudal portions of the NP, in effect creating duplicate NPs. In the caudal NP, ectopic FGF8 induced a second, inclusive area map, containing frontal cortex, S1, V1, and primary auditory areas. Moreover, duplicate S1 showed plasticity to sensory deprivation, and duplicate V1 responded to visual stimuli. Our findings implicate FGF8 as an organizer signal, and its source in the rostromedial telencephalon as an organizer of the neocortical area map.}, Author = {Assimacopoulos, Stavroula and Kao, Tina and Issa, Naoum P and Grove, Elizabeth A}, Date-Added = {2018-01-16 22:33:13 +0000}, Date-Modified = {2018-01-16 22:33:13 +0000}, Doi = {10.1523/JNEUROSCI.0071-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Brain Mapping; Electroporation; Female; Fibroblast Growth Factor 8; Male; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Morphogenesis; Neocortex; Neuronal Plasticity; Photic Stimulation; Pregnancy; Sensory Deprivation; Visual Perception}, Month = {May}, Number = {21}, Pages = {7191-201}, Pmc = {PMC3466079}, pmid = {22623663}, Pst = {ppublish}, Title = {Fibroblast growth factor 8 organizes the neocortical area map and regulates sensory map topography}, Volume = {32}, Year = {2012}, url = {papers/Assimacopoulos_JNeurosci2012.pdf}} @article{Demarque:2002, Abstract = {GABA and glutamate receptors are expressed in immature "silent" CA1 pyramidal neurons prior to synapse formation, but their function is unknown. We now report the presence of tonic, spontaneous, and evoked currents in embryonic and neonatal CA1 neurons mediated primarily by the activation of GABA(A) receptors. These currents are mediated by a nonconventional release of transmitters, as they persist in the presence of calcium channel blockers or botulinium toxin and are observed in Munc18-1-deficient mice in which vesicular release is abolished. This paracrine communication is modulated by glutamate but not GABA transporters, which do not operate during this period of life. Thus, a Ca(2+)- and SNARE-independent release of transmitters underlies a paracrine mode of communication before synapse formation.}, Author = {Demarque, Michael and Represa, Alfonso and Becq, H{\'e}l{\`e}ne and Khalilov, Ilgam and Ben-Ari, Yehezkel and Aniksztejn, Laurent}, Date-Added = {2018-01-16 22:30:38 +0000}, Date-Modified = {2018-01-16 22:32:50 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Excitatory Amino Acid Antagonists;Fetus;Cell Differentiation;Electric Stimulation;SNARE Proteins;Synapses;Paracrine Communication;Rats;Calcium Signaling;Animals;Glutamic Acid;Synaptic Transmission;21 Epilepsy;gamma-Aminobutyric Acid;Vesicular Transport Proteins;Pyramidal Cells;Calcium;Rats, Wistar;Hippocampus;Receptors, GABA-A;Mice, Knockout;21 Neurophysiology;Membrane Potentials;GABA Antagonists;Mice;24 Pubmed search results 2008;Membrane Proteins;Receptors, N-Methyl-D-Aspartate}, Mesh = {Animals; Calcium; Calcium Signaling; Cell Differentiation; Electric Stimulation; Excitatory Amino Acid Antagonists; Fetus; GABA Antagonists; GABA-A Receptor Antagonists; Glutamic Acid; Hippocampus; Membrane Potentials; Membrane Proteins; Mice; Mice, Knockout; Paracrine Communication; Pyramidal Cells; Rats; Rats, Wistar; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; SNARE Proteins; Synapses; Synaptic Transmission; Vesicular Transport Proteins; gamma-Aminobutyric Acid}, Month = {Dec}, Number = {6}, Pages = {1051-61}, pmid = {12495621}, Pst = {ppublish}, Title = {Paracrine intercellular communication by a Ca2+- and SNARE-independent release of GABA and glutamate prior to synapse formation}, Volume = {36}, Year = {2002}, url = {papers/Demarque_Neuron2002.pdf}} @article{Clarkson:2016, Abstract = {Sex differences in brain neuroanatomy and neurophysiology underpin considerable physiological and behavioural differences between females and males. Sexual differentiation of the brain is regulated by testosterone secreted by the testes predominantly during embryogenesis in humans and the neonatal period in rodents. Despite huge advances in understanding how testosterone, and its metabolite oestradiol, sexually differentiate the brain, little is known about the mechanism that actually generates the male-specific neonatal testosterone surge. This review examines the evidence for the role of the hypothalamus, and particularly the gonadotropin-releasing hormone (GnRH) neurons, in generating the neonatal testosterone surge in rodents and primates. Kisspeptin-GPR54 signalling is well established as a potent and critical regulator of GnRH neuron activity during puberty and adulthood, and we argue here for an equally important role at birth in driving the male-specific neonatal testosterone surge in rodents. The presence of a male-specific population of preoptic area kisspeptin neurons that appear transiently in the perinatal period provide one possible source of kisspeptin drive to neonatal GnRH neurons in the mouse.}, Author = {Clarkson, Jenny and Herbison, Allan E}, Date-Added = {2018-01-16 22:30:11 +0000}, Date-Modified = {2018-01-16 22:30:11 +0000}, Doi = {10.1098/rstb.2015.0115}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {GPR54; GnRH; kisspeptin; sexual differentiation; testosterone}, Mesh = {Animals; Animals, Newborn; Gene Expression Regulation, Developmental; Gonadotropin-Releasing Hormone; Hypothalamus; Male; Testosterone}, Month = {Feb}, Number = {1688}, Pages = {20150115}, Pmc = {PMC4785901}, pmid = {26833836}, Pst = {ppublish}, Title = {Hypothalamic control of the male neonatal testosterone surge}, Volume = {371}, Year = {2016}, url = {papers/Clarkson_PhilosTransRSocLondBBiolSci2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1098/rstb.2015.0115}} @article{Turing:1952, Abstract = {It is suggested that a system of chemical substances, called morphogens, reacting together and diffusing through a tissue, is adequate to account for the main phenomena of morphogenesis. Such a system, although it may originally be quite homogeneous, may later develop a pattern or structure due to an instability of the homogeneous equilibrium, which is triggered off by random disturbances. Such reaction-diffusion systems are considered in some detail in the case of an isolated ring of cells, a mathematically convenient, though biologically unusual system. The investigation is chiefly concerned with the onset of instability. It is found that there are six essentially different forms which this may take. In the most interesting form stationary waves appear on the ring. It is suggested that this might account, for instance, for the tentacle patterns on Hydra and for whorled leaves. A system of reactions and diffusion on a sphere is also considered. Such a system appears to account for gastrulation. Another reaction system in two dimensions gives rise to patterns reminiscent of dappling. It is also suggested that stationary waves in two dimensions could account for the phenomena of phyllotaxis. The purpose of this paper is to discuss a possible mechanism by which the genes of a zygote may determine the anatomical structure of the resulting organism. The theory does not make any new hypotheses; it merely suggests that certain well-known physical laws are sufficient to account for many of the facts. The full understanding of the paper requires a good knowledge of mathematics, some biology, and some elementary chemistry. Since readers cannot be expected to be experts in all of these subjects, a number of elementary facts are explained, which can be found in text-books, but whose omission would make the paper difficult reading.}, Author = {A. M. Turing}, Date-Added = {2018-01-16 22:20:28 +0000}, Date-Modified = {2018-01-16 22:21:29 +0000}, Issn = {00804622}, Journal = {Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences}, Number = {641}, Pages = {37-72}, Publisher = {The Royal Society}, Title = {The Chemical Basis of Morphogenesis}, eprint = {http://www.jstor.org/stable/92463}, Volume = {237}, Year = {1952}, url = {papers/Turing_PhilosophicalTransactionsoftheRoyalSocietyofLondon.SeriesB,BiologicalSciences1952.pdf}} @article{Dalva:2007, Abstract = {Many cell adhesion molecules are localized at synaptic sites in neuronal axons and dendrites. These molecules bridge pre- and postsynaptic specializations but do far more than simply provide a mechanical link between cells. In this review, we will discuss the roles these proteins have during development and at mature synapses. Synaptic adhesion proteins participate in the formation, maturation, function and plasticity of synaptic connections. Together with conventional synaptic transmission mechanisms, these molecules are an important element in the trans-cellular communication mediated by synapses.}, Author = {Dalva, Matthew B and McClelland, Andrew C and Kayser, Matthew S}, Date-Added = {2018-01-16 22:15:29 +0000}, Date-Modified = {2018-01-16 22:15:29 +0000}, Doi = {10.1038/nrn2075}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Cell Adhesion Molecules; Models, Biological; Signal Transduction; Synapses}, Month = {Mar}, Number = {3}, Pages = {206-20}, Pmc = {PMC4756920}, pmid = {17299456}, Pst = {ppublish}, Title = {Cell adhesion molecules: signalling functions at the synapse}, Volume = {8}, Year = {2007}, url = {papers/Dalva_NatRevNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2075}} @article{Zuloaga:2014, Abstract = {Estrogen receptors regulate multiple brain functions, including stress, sexual, and memory-associated behaviors as well as controlling neuroendocrine and autonomic function. During development, estrogen signaling is involved in programming adult sex differences in physiology and behavior. Expression of estrogen receptor α changes across development in a region-specific fashion. By contrast, estrogen receptor β (ERβ) is expressed in many brain regions, yet few studies have explored sex and developmental differences in its expression, largely because of the absence of selective reagents for anatomical localization of the protein. This study utilized bacterial artificial chromosome transgenic mice expressing ERβ identified by enhanced green fluorescent protein (EGFP) to compare expression levels and distribution of ERβ in the male and female mouse forebrain on the day of birth (P0), on postnatal day 4 (P4), and on P21. By using qualitative analysis, we mapped the distribution of ERβ-EGFP and found developmental alterations in ERβ expression within the cortex, hippocampus, and hypothalamic regions including the arcuate, ventromedial, and paraventricular nuclei. We also report a sex difference in ERβ in the bed nucleus of the stria terminalis, with males showing greater expression at P4 and P21. Another sex difference was found in the anteroventral periventricular nucleus of P21, but not P0 or P4, mice, in which ERβ-EGFP-immunoreactive cells were densely clustered near the third ventricle in females but not males. These developmental changes and sex differences in ERβ indicate a mechanism through which estrogens might differentially affect brain functions or program adult physiology at select times during development.}, Author = {Zuloaga, Damian G and Zuloaga, Kristen L and Hinds, Laura R and Carbone, David L and Handa, Robert J}, Date-Added = {2018-01-16 22:14:36 +0000}, Date-Modified = {2018-01-16 22:14:36 +0000}, Doi = {10.1002/cne.23400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {Esr2; age; development; estrogen receptor; estrogen receptor β; forebrain; sex difference}, Mesh = {Age Factors; Animals; Chromosomes, Artificial, Bacterial; Estrogen Receptor beta; Female; Immunohistochemistry; Male; Mice; Mice, Transgenic; Prosencephalon; Sex Characteristics}, Month = {Feb}, Number = {2}, Pages = {358-71}, Pmc = {PMC4815281}, pmid = {23818057}, Pst = {ppublish}, Title = {Estrogen receptor β expression in the mouse forebrain: age and sex differences}, Volume = {522}, Year = {2014}, url = {papers/Zuloaga_JCompNeurol2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.23400}} @incollection{Puelles20153, Abstract = {Abstract Rodent brain gene patterns are readily comparable with counterparts in the human, avian, reptilian, amphibian, teleost, shark and agnathan species. This scenario provides substantial novel evidence for comparative neuroanatomy, both corroborating some earlier conclusions and calling for revision of other concepts. In recent years accumulated observations have shown that gene expression patterns frequently display reproducible boundaries; these tend to be aligned with the axial and dorsoventral dimensions of the neural tube and are topologically invariant during ontogenesis. Many early molecular patterns are remarkably resistant to evolutionary change. Accumulated comparative results over the last decade strongly indicate that there is a common pattern of differentially-specified neural regions among all vertebrates. This chapter studies the molecular approaches to understanding the structural and functional organization of the nervous system which promise new insights into modular brain domains conserved among various species. Fate-map analysis suggests that early differential molecular specification of progenitor regions and subregions in the neural plate and neural tube eventually correlates with specific prospective fates via patterned proliferation, neurogenesis and differentiation. }, Address = {San Diego}, Author = {Luis Puelles and Salvador Mart{\'\i}nez and Margaret Mart{\'\i}nez-De-La-Torre and John L.R. Rubenstein}, Booktitle = {The Rat Nervous System (Fourth Edition)}, Date-Added = {2018-01-16 22:12:46 +0000}, Date-Modified = {2018-01-16 22:12:46 +0000}, Doi = {https://doi.org/10.1016/B978-0-12-374245-2.00001-2}, Edition = {Fourth Edition}, Editor = {Paxinos, George}, Isbn = {978-0-12-374245-2}, Keywords = {Vertebrates}, Pages = {3 - 24}, Publisher = {Academic Press}, Title = {Chapter 1 - Gene Maps and Related Histogenetic Domains in the Forebrain and Midbrain}, eprint = {https://www.sciencedirect.com/science/article/pii/B9780123742452000012}, Year = {2015}, url = {papers/Puelles_2015.pdf}} @article{Schlaggar:2011, Abstract = {In this issue of Neuron, Chen and colleagues combine structural MRI and a twin-study design to investigate the influence of genetics on human cortical regionalization. Their results resonate with findings from animal studies and certain human syndromes of developmental cortical malformation.}, Author = {Schlaggar, Bradley L}, Date-Added = {2018-01-16 22:11:15 +0000}, Date-Modified = {2018-01-16 22:11:15 +0000}, Doi = {10.1016/j.neuron.2011.10.024}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Brain; Cerebral Cortex; Gene Expression Regulation, Developmental; Humans; Male; Twins}, Month = {Nov}, Number = {4}, Pages = {499-501}, Pmc = {PMC3226785}, pmid = {22099452}, Pst = {ppublish}, Title = {Mapping genetic influences on cortical regionalization}, Volume = {72}, Year = {2011}, url = {papers/Schlaggar_Neuron2011.pdf}} @article{Groten:2013, Abstract = {Although the contribution of Ca(2+) buffering systems can vary between neuronal types and cellular compartments, it is unknown whether distinct Ca(2+) sources within a neuron have different buffers. As individual Ca(2+) sources can have separate functions, we propose that each is handled by unique systems. Using Aplysia californica bag cell neurons, which initiate reproduction through an afterdischarge involving multiple Ca(2+)-dependent processes, we investigated the role of endoplasmic reticulum (ER) and mitochondrial sequestration, as well as extrusion via the plasma membrane Ca(2+)-ATPase (PMCA) and Na(+)/Ca(2+) exchanger, to the clearance of voltage-gated Ca(2+) influx, Ca(2+)-induced Ca(2+)-release (CICR), and store-operated Ca(2+) influx. Cultured bag cell neurons were filled with the Ca(2+) indicator, fura-PE3, to image Ca(2+) under whole-cell voltage clamp. A 5 Hz, 1 min train of depolarizing voltage steps elicited voltage-gated Ca(2+) influx followed by EGTA-sensitive CICR from the mitochondria. A compartment model of Ca(2+) indicated the effect of EGTA on CICR was due to buffering of released mitochondrial Ca(2+) rather than uptake competition. Removal of voltage-gated Ca(2+) influx was dominated by the mitochondria and PMCA, with no contribution from the Na(+)/Ca(2+) exchanger or sarcoplasmic/endoplasmic Ca(2+)-ATPase (SERCA). In contrast, CICR recovery was slowed by eliminating the Na(+)/Ca(2+) exchanger and PMCA. Last, store-operated influx, evoked by ER depletion, was removed by the SERCA and depended on the mitochondrial membrane potential. Our results demonstrate that distinct buffering systems are dedicated to particular Ca(2+) sources. In general, this may represent a means to differentially regulate Ca(2+)-dependent processes, and for Aplysia, influence how reproductive behavior is triggered.}, Author = {Groten, Christopher J and Rebane, Jonathan T and Blohm, Gunnar and Magoski, Neil S}, Date-Added = {2018-01-16 22:11:02 +0000}, Date-Modified = {2018-01-16 22:11:02 +0000}, Doi = {10.1523/JNEUROSCI.6384-11.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Aplysia; Calcium; Cells, Cultured; Egtazic Acid; Endoplasmic Reticulum; Membrane Potentials; Mitochondria; Molecular Imaging; Neuroendocrine Cells; Neurons; Plasma Membrane Calcium-Transporting ATPases; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Sodium-Calcium Exchanger}, Month = {Apr}, Number = {15}, Pages = {6476-91}, pmid = {23575846}, Pst = {ppublish}, Title = {Separate Ca2+ sources are buffered by distinct Ca2+ handling systems in aplysia neuroendocrine cells}, Volume = {33}, Year = {2013}, url = {papers/Groten_JNeurosci2013.pdf}} @article{Suarez:2014a, Abstract = {Axonal connections between the left and right sides of the brain are crucial for bilateral integration of lateralized sensory, motor, and associative functions. Throughout vertebrate species, forebrain commissures share a conserved developmental plan, a similar position relative to each other within the brain and similar patterns of connectivity. However, major events in the evolution of the vertebrate brain, such as the expansion of the telencephalon in tetrapods and the origin of the six-layered isocortex in mammals, resulted in the emergence and diversification of new commissural routes. These new interhemispheric connections include the pallial commissure, which appeared in the ancestors of tetrapods and connects the left and right sides of the medial pallium (hippocampus in mammals), and the corpus callosum, which is exclusive to eutherian (placental) mammals and connects both isocortical hemispheres. A comparative analysis of commissural systems in vertebrates reveals that the emergence of new commissural routes may have involved co-option of developmental mechanisms and anatomical substrates of preexistent commissural pathways. One of the embryonic regions of interest for studying these processes is the commissural plate, a portion of the early telencephalic midline that provides molecular specification and a cellular scaffold for the development of commissural axons. Further investigations into these embryonic processes in carefully selected species will provide insights not only into the mechanisms driving commissural evolution, but also regarding more general biological problems such as the role of developmental plasticity in evolutionary change.}, Author = {Su{\'a}rez, Rodrigo and Gobius, Ilan and Richards, Linda J}, Date-Added = {2018-01-16 22:08:37 +0000}, Date-Modified = {2018-01-16 22:08:37 +0000}, Doi = {10.3389/fnhum.2014.00497}, Journal = {Front Hum Neurosci}, Journal-Full = {Frontiers in human neuroscience}, Keywords = {anterior commissure; axon guidance; commissural plate; comparative neuroanatomy; corpus callosum; hippocampal commissure}, Pages = {497}, Pmc = {PMC4094842}, pmid = {25071525}, Pst = {epublish}, Title = {Evolution and development of interhemispheric connections in the vertebrate forebrain}, Volume = {8}, Year = {2014}, url = {papers/Suárez_FrontHumNeurosci2014.pdf}} @article{Jones:2016, Abstract = {Though both clinicians and scientists have long recognized the influence of extracellular calcium on the function of muscle and nervous tissue, recent insights reveal that the mechanisms allowing changes in extracellular calcium to alter cellular excitability have been incompletely understood. For many years the effects of calcium on neuronal signaling were explained only in terms of calcium entry through voltage-gated calcium channels and biophysical charge screening. More recently however, it has been recognized that the calcium-sensing receptor is prevalent in the nervous system and regulates synaptic transmission and neuronal activity via multiple signaling pathways. Here we review the multiplicity of mechanisms by which changes in extracellular calcium alter neuronal signaling and propose that multiple mechanisms are required to describe the full range of experimental observations.}, Author = {Jones, Brian L and Smith, Stephen M}, Date-Added = {2018-01-16 22:08:12 +0000}, Date-Modified = {2018-01-16 22:08:12 +0000}, Doi = {10.3389/fphys.2016.00116}, Journal = {Front Physiol}, Journal-Full = {Frontiers in physiology}, Keywords = {action potentials; calcium; calcium sensing receptor; excitability; ion channels; nervous system; synaptic transmission}, Pages = {116}, Pmc = {PMC4811949}, pmid = {27065884}, Pst = {epublish}, Title = {Calcium-Sensing Receptor: A Key Target for Extracellular Calcium Signaling in Neurons}, Volume = {7}, Year = {2016}, url = {papers/Jones_FrontPhysiol2016.pdf}} @article{Greig:2016, Abstract = {While transcriptional controls over the size and relative position of cortical areas have been identified, less is known about regulators that direct acquisition of area-specific characteristics. Here, we report that the transcription factor Ctip1 functions in primary sensory areas to repress motor and activate sensory programs of gene expression, enabling establishment of sharp molecular boundaries defining functional areas. In Ctip1 mutants, abnormal gene expression leads to aberrantly motorized corticocortical and corticofugal output connectivity. Ctip1 critically regulates differentiation of layer IV neurons, and selective loss of Ctip1 in cortex deprives thalamocortical axons of their receptive "sensory field" in layer IV, which normally provides a tangentially and radially defined compartment of dedicated synaptic territory. Therefore, although thalamocortical axons invade appropriate cortical regions, they are unable to organize into properly configured sensory maps. Together, these data identify Ctip1 as a critical control over sensory area development.}, Author = {Greig, Luciano C and Woodworth, Mollie B and Greppi, Chlo{\'e} and Macklis, Jeffrey D}, Date-Added = {2018-01-16 22:01:17 +0000}, Date-Modified = {2018-01-16 22:01:17 +0000}, Doi = {10.1016/j.neuron.2016.03.008}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Axons; Carrier Proteins; Cell Differentiation; Gene Expression Regulation, Developmental; Mice; Mice, Knockout; Mutation; Neocortex; Neurons; Nuclear Proteins; Signal Transduction; Thalamus}, Month = {04}, Number = {2}, Pages = {261-77}, Pmc = {PMC4873772}, pmid = {27100196}, Pst = {ppublish}, Title = {Ctip1 Controls Acquisition of Sensory Area Identity and Establishment of Sensory Input Fields in the Developing Neocortex}, Volume = {90}, Year = {2016}, url = {papers/Greig_Neuron2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2016.03.008}} @article{Ypsilanti:2016, Abstract = {The development of the cortex is an elaborate process that integrates a plethora of finely tuned molecular processes ranging from carefully regulated gradients of transcription factors, dynamic changes in the chromatin landscape, or formation of protein complexes to elicit and regulate transcription. Combined with cellular processes such as cell type specification, proliferation, differentiation, and migration, all of these developmental processes result in the establishment of an adult mammalian cortex with its typical lamination and regional patterning. By examining in-depth the role of one transcription factor, Pax6, on the regulation of cortical development, its integration in the regulation of chromatin state, and its regulation by cis-regulatory elements, we aim to demonstrate the importance of integrating each level of regulation in our understanding of cortical development.}, Author = {Ypsilanti, Ath{\'e}na R and Rubenstein, John L R}, Date-Added = {2018-01-16 22:00:12 +0000}, Date-Modified = {2018-01-16 22:00:12 +0000}, Doi = {10.1002/cne.23866}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {Chromatin; Epigenetics; Pax6; Transcription; cortex; cortical development}, Mesh = {Animals; Biological Evolution; Cerebral Cortex; Chromatin; Chromatin Assembly and Disassembly; Epigenesis, Genetic; Eye Proteins; Homeodomain Proteins; Humans; PAX6 Transcription Factor; Paired Box Transcription Factors; Repressor Proteins}, Month = {Feb}, Number = {3}, Pages = {609-29}, Pmc = {PMC4706819}, pmid = {26304102}, Pst = {ppublish}, Title = {Transcriptional and epigenetic mechanisms of early cortical development: An examination of how Pax6 coordinates cortical development}, Volume = {524}, Year = {2016}, url = {papers/Ypsilanti_JCompNeurol2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.23866}} @article{Furchtgott:2017, Abstract = {Computational analysis of gene expression to determine both the sequence of lineage choices made by multipotent cells and to identify the genes influencing these decisions is challenging. Here we discover a pattern in the expression levels of a sparse subset of genes among cell types in B- and T-cell developmental lineages that correlates with developmental topologies. We develop a statistical framework using this pattern to simultaneously infer lineage transitions and the genes that determine these relationships. We use this technique to reconstruct the early hematopoietic and intestinal developmental trees. We extend this framework to analyze single-cell RNA-seq data from early human cortical development, inferring a neocortical-hindbrain split in early progenitor cells and the key genes that could control this lineage decision. Our work allows us to simultaneously infer both the identity and lineage of cell types as well as a small set of key genes whose expression patterns reflect these relationships.}, Author = {Furchtgott, Leon A and Melton, Samuel and Menon, Vilas and Ramanathan, Sharad}, Date-Added = {2018-01-16 21:58:50 +0000}, Date-Modified = {2018-01-16 21:58:50 +0000}, Doi = {10.7554/eLife.20488}, Journal = {Elife}, Journal-Full = {eLife}, Keywords = {Transcriptomics; computational biology; developmental biology; human; mouse; stem cells; systems biology}, Month = {Mar}, Pmc = {PMC5352226}, pmid = {28296636}, Pst = {epublish}, Title = {Discovering sparse transcription factor codes for cell states and state transitions during development}, Volume = {6}, Year = {2017}, url = {papers/Furchtgott_Elife2017.pdf}} @article{Homman-Ludiye:2014, Abstract = {The integration of the visual stimulus takes place at the level of the neocortex, organized in anatomically distinct and functionally unique areas. Primates, including humans, are heavily dependent on vision, with approximately 50% of their neocortical surface dedicated to visual processing and possess many more visual areas than any other mammal, making them the model of choice to study visual cortical arealisation. However, in order to identify the mechanisms responsible for patterning the developing neocortex, specifying area identity as well as elucidate events that have enabled the evolution of the complex primate visual cortex, it is essential to gain access to the cortical maps of alternative species. To this end, species including the mouse have driven the identification of cellular markers, which possess an area-specific expression profile, the development of new tools to label connections and technological advance in imaging techniques enabling monitoring of cortical activity in a behaving animal. In this review we present non-primate species that have contributed to elucidating the evolution and development of the visual cortex. We describe the current understanding of the mechanisms supporting the establishment of areal borders during development, mainly gained in the mouse thanks to the availability of genetically modified lines but also the limitations of the mouse model and the need for alternate species.}, Author = {Homman-Ludiye, Jihane and Bourne, James A}, Date-Added = {2018-01-16 21:57:26 +0000}, Date-Modified = {2018-01-16 21:57:26 +0000}, Doi = {10.3389/fncir.2014.00079}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {cell markers; cortical patterning; guidance molecules; neocortex}, Mesh = {Animals; Biological Evolution; Brain Mapping; Nerve Tissue Proteins; Neurons; Visual Cortex; Visual Pathways}, Pages = {79}, Pmc = {PMC4081835}, pmid = {25071460}, Pst = {epublish}, Title = {Mapping arealisation of the visual cortex of non-primate species: lessons for development and evolution}, Volume = {8}, Year = {2014}, url = {papers/Homman-Ludiye_FrontNeuralCircuits2014.pdf}, Bdsk-File-2 = {papers/Homman-Ludiye_FrontNeuralCircuits2014.jpg}} @article{Fenlon:2013, Author = {Fenlon, Laura R and Su{\'a}rez, Rodrigo}, Date-Added = {2018-01-16 21:56:20 +0000}, Date-Modified = {2018-01-16 21:56:20 +0000}, Doi = {10.1523/JNEUROSCI.2859-13.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Gene Expression Regulation, Developmental; Neocortex; Thalamus}, Month = {Aug}, Number = {35}, Pages = {13938-9}, pmid = {23986230}, Pst = {ppublish}, Title = {Thalamic afferents and neocortical arealization: an ongoing journey}, Volume = {33}, Year = {2013}, url = {papers/Fenlon_JNeurosci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2859-13.2013}} @article{Pouchelon:2014, Abstract = {PURPOSE OF REVIEW: Neocortical and thalamic interactions are necessary for the execution of complex sensory-motor tasks and associated cognitive processes. Investigation of thalamocortical circuit development is therefore critical to understand developmental disorders involving abnormal cortical function. Here, we review recent advances in our understanding of thalamus-dependent cortical patterning and cortical neuron differentiation. RECENT FINDINGS: Although the principles of cortical map patterning are increasingly understood, the extent to which thalamocortical inputs contribute to cortical neuron differentiation is still unclear. The recent development of genetic models allowing cell-type-specific dissection of cortical input pathways has shed light on some of the input-dependent and activity-dependent processes occurring during cortical development, which are discussed here. SUMMARY: These recent studies have revealed interwoven links between thalamic and cortical neurons, in which cell intrinsic differentiation programs are tightly regulated by synaptic input during a prolonged period of development. Challenges in the years to come will be to identify the mechanisms underlying the reciprocal interactions between intrinsic and extrinsic differentiation programs, and their contribution to neurodevelopmental disorders and neuropsychiatric disorders at large.}, Author = {Pouchelon, Gabrielle and Jabaudon, Denis}, Date-Added = {2018-01-16 21:54:34 +0000}, Date-Modified = {2018-01-16 21:54:34 +0000}, Doi = {10.1097/WCO.0000000000000070}, Journal = {Curr Opin Neurol}, Journal-Full = {Current opinion in neurology}, Mesh = {Animals; Brain Mapping; Humans; Neocortex; Nerve Net; Neural Pathways; Neurogenesis; Neurons; Thalamus}, Month = {Apr}, Number = {2}, Pages = {142-8}, pmid = {24553463}, Pst = {ppublish}, Title = {Nurturing the cortex's thalamic nature}, Volume = {27}, Year = {2014}, Bdsk-Url-1 = {http://dx.doi.org/10.1097/WCO.0000000000000070}} @article{Jabaudon:2017, Author = {Jabaudon, Denis}, Date-Added = {2018-01-16 21:53:47 +0000}, Date-Modified = {2018-01-16 21:53:47 +0000}, Doi = {10.1038/ncomms16042}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Month = {Jul}, Pages = {16042}, Pmc = {PMC5500875}, pmid = {28671189}, Pst = {epublish}, Title = {Fate and freedom in developing neocortical circuits}, Volume = {8}, Year = {2017}, url = {papers/Jabaudon_NatCommun2017.pdf}} @article{Frangeul:2016, Abstract = {Modality-specific sensory inputs from individual sense organs are processed in parallel in distinct areas of the neocortex. For each sensory modality, input follows a cortico-thalamo-cortical loop in which a 'first-order' exteroceptive thalamic nucleus sends peripheral input to the primary sensory cortex, which projects back to a 'higher order' thalamic nucleus that targets a secondary sensory cortex. This conserved circuit motif raises the possibility that shared genetic programs exist across sensory modalities. Here we report that, despite their association with distinct sensory modalities, first-order nuclei in mice are genetically homologous across somatosensory, visual, and auditory pathways, as are higher order nuclei. We further reveal peripheral input-dependent control over the transcriptional identity and connectivity of first-order nuclei by showing that input ablation leads to induction of higher-order-type transcriptional programs and rewiring of higher-order-directed descending cortical input to deprived first-order nuclei. These findings uncover an input-dependent genetic logic for the design and plasticity of sensory pathways, in which conserved developmental programs lead to conserved circuit motifs across sensory modalities.}, Author = {Frangeul, Laura and Pouchelon, Gabrielle and Telley, Ludovic and Lefort, Sandrine and Luscher, Christian and Jabaudon, Denis}, Date-Added = {2018-01-16 21:49:52 +0000}, Date-Modified = {2018-01-16 21:49:52 +0000}, Doi = {10.1038/nature19770}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Afferent Pathways; Animals; Auditory Pathways; Female; Gene Expression Regulation, Developmental; Geniculate Bodies; Male; Mice; Mice, Inbred C57BL; Models, Genetic; Neuronal Plasticity; Somatosensory Cortex; Thalamic Nuclei; Transcription, Genetic; Visual Pathways}, Month = {Oct}, Number = {7623}, Pages = {96-98}, pmid = {27669022}, Pst = {ppublish}, Title = {A cross-modal genetic framework for the development and plasticity of sensory pathways}, Volume = {538}, Year = {2016}, url = {papers/Frangeul_Nature2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature19770}} @article{Marques-Smith:2016, Abstract = {GABAergic activity is thought to influence developing neocortical sensory circuits. Yet the late postnatal maturation of local layer (L)4 circuits suggests alternate sources of GABAergic control in nascent thalamocortical networks. We show that a population of L5b, somatostatin (SST)-positive interneuron receives early thalamic synaptic input and, using laser-scanning photostimulation, identify an early transient circuit between these cells and L4 spiny stellates (SSNs) that disappears by the end of the L4 critical period. Sensory perturbation disrupts the transition to a local GABAergic circuit, suggesting a link between translaminar and local control of SSNs. Conditional silencing of SST+ interneurons or conversely biasing the circuit toward local inhibition by overexpression of neuregulin-1 type 1 results in an absence of early L5b GABAergic input in mutants and delayed thalamic innervation of SSNs. These data identify a role for L5b SST+ interneurons in the control of SSNs in the early postnatal neocortex.}, Author = {Marques-Smith, Andre and Lyngholm, Daniel and Kaufmann, Anna-Kristin and Stacey, Jacqueline A and Hoerder-Suabedissen, Anna and Becker, Esther B E and Wilson, Michael C and Moln{\'a}r, Zolt{\'a}n and Butt, Simon J B}, Date-Added = {2018-01-16 21:47:09 +0000}, Date-Modified = {2018-01-16 21:48:58 +0000}, Doi = {10.1016/j.neuron.2016.01.015}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {development; Circuits; activity-development; interneurons; Transient; Neocortex; isocortex}, Mesh = {Animals; Electric Stimulation; Female; Interneurons; Male; Membrane Potentials; Mice; Mice, Transgenic; Neural Pathways; Neuregulin-1; Photic Stimulation; Somatosensory Cortex; Somatostatin; Thalamus; gamma-Aminobutyric Acid}, Month = {Feb}, Number = {3}, Pages = {536-49}, Pmc = {PMC4742537}, pmid = {26844833}, Pst = {ppublish}, Title = {A Transient Translaminar GABAergic Interneuron Circuit Connects Thalamocortical Recipient Layers in Neonatal Somatosensory Cortex}, Volume = {89}, Year = {2016}, url = {papers/Marques-Smith_Neuron2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2016.01.015}} @article{Ji:2015, Abstract = {Layer 1 (L1) of primary visual cortex (V1) is the target of projections from many brain regions outside of V1. We found that inputs to the non-columnar mouse V1 from the dorsal lateral geniculate nucleus and feedback projections from multiple higher cortical areas to L1 are patchy. The patches are matched to a pattern of M2 muscarinic acetylcholine receptor expression at fixed locations of mouse, rat, and monkey V1. Neurons in L2/3 aligned with M2-rich patches have high spatial acuity, whereas cells in M2-poor zones exhibited high temporal acuity. Together M2+ and M2- zones form constant-size domains that are repeated across V1. Domains map subregions of the receptive field, such that multiple copies are contained within the point image. The results suggest that the modular network in mouse V1 selects spatiotemporally distinct clusters of neurons within the point image for top-down control and differential routing of inputs to cortical streams.}, Author = {Ji, Weiqing and G{\u a}m{\u a}nu{\c t}, R{\u a}zvan and Bista, Pawan and D'Souza, Rinaldo D and Wang, Quanxin and Burkhalter, Andreas}, Date-Added = {2018-01-16 21:09:24 +0000}, Date-Modified = {2018-01-16 21:09:24 +0000}, Doi = {10.1016/j.neuron.2015.07.004}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Female; Haplorhini; Male; Mice; Mice, Inbred C57BL; Nerve Net; Photic Stimulation; Rats; Rats, Long-Evans; Visual Cortex; Visual Pathways}, Month = {Aug}, Number = {3}, Pages = {632-43}, Pmc = {PMC4529541}, pmid = {26247867}, Pst = {ppublish}, Title = {Modularity in the Organization of Mouse Primary Visual Cortex}, Volume = {87}, Year = {2015}, url = {papers/Ji_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.07.004}} @article{Chou:2013, Abstract = {Studies of area patterning of the neocortex have focused on primary areas, concluding that the primary visual area, V1, is specified by transcription factors (TFs) expressed by progenitors. Mechanisms that determine higher-order visual areas (V(HO)) and distinguish them from V1 are unknown. We demonstrated a requirement for thalamocortical axon (TCA) input by genetically deleting geniculocortical TCAs and showed that they drive differentiation of patterned gene expression that distinguishes V1 and V(HO). Our findings suggest a multistage process for area patterning: TFs expressed by progenitors specify an occipital visual cortical field that differentiates into V1 and V(HO); this latter phase requires geniculocortical TCA input to the nascent V1 that determines genetic distinctions between V1 and V(HO) for all layers and ultimately determines their area-specific functional properties.}, Author = {Chou, Shen-Ju and Babot, Zoila and Leing{\"a}rtner, Axel and Studer, Michele and Nakagawa, Yasushi and O'Leary, Dennis D M}, Date-Added = {2018-01-16 21:08:09 +0000}, Date-Modified = {2018-01-16 21:08:09 +0000}, Doi = {10.1126/science.1232806}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Animals; Axons; Gene Deletion; Gene Expression Regulation; Genetic Markers; Mice; Mice, Knockout; Neocortex; Neural Stem Cells; Thalamus; Transcription Factors; Visual Cortex; Visual Fields}, Month = {Jun}, Number = {6137}, Pages = {1239-42}, Pmc = {PMC3851411}, pmid = {23744949}, Pst = {ppublish}, Title = {Geniculocortical input drives genetic distinctions between primary and higher-order visual areas}, Volume = {340}, Year = {2013}, url = {papers/Chou_Science2013.pdf}, Bdsk-File-2 = {papers/Chou_Science2013a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1232806}} @article{Bourane:2015, Abstract = {Sensory circuits in the dorsal spinal cord integrate and transmit multiple cutaneous sensory modalities including the sense of light touch. Here, we identify a population of excitatory interneurons (INs) in the dorsal horn that are important for transmitting innocuous light touch sensation. These neurons express the ROR alpha (RORα) nuclear orphan receptor and are selectively innervated by cutaneous low threshold mechanoreceptors (LTMs). Targeted removal of RORα INs in the dorsal spinal cord leads to a marked reduction in behavioral responsiveness to light touch without affecting responses to noxious and itch stimuli. RORα IN-deficient mice also display a selective deficit in corrective foot movements. This phenotype, together with our demonstration that the RORα INs are innervated by corticospinal and vestibulospinal projection neurons, argues that the RORα INs direct corrective reflex movements by integrating touch information with descending motor commands from the cortex and cerebellum.}, Author = {Bourane, Steeve and Grossmann, Katja S and Britz, Olivier and Dalet, Antoine and Del Barrio, Marta Garcia and Stam, Floor J and Garcia-Campmany, Lidia and Koch, Stephanie and Goulding, Martyn}, Date-Added = {2018-01-16 21:07:27 +0000}, Date-Modified = {2018-01-16 21:07:27 +0000}, Doi = {10.1016/j.cell.2015.01.011}, Journal = {Cell}, Journal-Full = {Cell}, Mesh = {Animals; Interneurons; Mechanotransduction, Cellular; Mice; Motor Activity; Motor Neurons; Neural Pathways; Nuclear Receptor Subfamily 1, Group F, Member 1; Spinal Cord Dorsal Horn; Synapses; Touch}, Month = {Jan}, Number = {3}, Pages = {503-15}, Pmc = {PMC4431637}, pmid = {25635458}, Pst = {ppublish}, Title = {Identification of a spinal circuit for light touch and fine motor control}, Volume = {160}, Year = {2015}, url = {papers/Bourane_Cell2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2015.01.011}} @article{Sun:2014, Abstract = {The size and extent of folding of the mammalian cerebral cortex are important factors that influence a species' cognitive abilities and sensorimotor skills. Studies in various animal models and in humans have provided insight into the mechanisms that regulate cortical growth and folding. Both protein-coding genes and microRNAs control cortical size, and recent progress in characterizing basal progenitor cells and the genes that regulate their proliferation has contributed to our understanding of cortical folding. Neurological disorders linked to disruptions in cortical growth and folding have been associated with novel neurogenetic mechanisms and aberrant signalling pathways, and these findings have changed concepts of brain evolution and may lead to new medical treatments for certain disorders.}, Author = {Sun, Tao and Hevner, Robert F}, Date-Added = {2018-01-16 21:04:52 +0000}, Date-Modified = {2018-01-16 21:04:52 +0000}, Doi = {10.1038/nrn3707}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Biological Evolution; Cerebral Cortex; Humans; Neural Stem Cells}, Month = {Apr}, Number = {4}, Pages = {217-32}, Pmc = {PMC4107216}, pmid = {24646670}, Pst = {ppublish}, Title = {Growth and folding of the mammalian cerebral cortex: from molecules to malformations}, Volume = {15}, Year = {2014}, url = {papers/Sun_NatRevNeurosci2014.pdf}} @article{Harris:2015, Abstract = {Similarities in neocortical circuit organization across areas and species suggest a common strategy to process diverse types of information, including sensation from diverse modalities, motor control and higher cognitive processes. Cortical neurons belong to a small number of main classes. The properties of these classes, including their local and long-range connectivity, developmental history, gene expression, intrinsic physiology and in vivo activity patterns, are remarkably similar across areas. Each class contains subclasses; for a rapidly growing number of these, conserved patterns of input and output connections are also becoming evident. The ensemble of circuit connections constitutes a basic circuit pattern that appears to be repeated across neocortical areas, with area- and species-specific modifications. Such 'serially homologous' organization may adapt individual neocortical regions to the type of information each must process.}, Author = {Harris, Kenneth D and Shepherd, Gordon M G}, Date-Added = {2018-01-16 21:04:43 +0000}, Date-Modified = {2018-01-16 21:04:43 +0000}, Doi = {10.1038/nn.3917}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Animals; Humans; Interneurons; Neocortex; Nerve Net}, Month = {Feb}, Number = {2}, Pages = {170-81}, Pmc = {PMC4889215}, pmid = {25622573}, Pst = {ppublish}, Title = {The neocortical circuit: themes and variations}, Volume = {18}, Year = {2015}, url = {papers/Harris_NatNeurosci2015.pdf}} @article{Alfano:2014, Abstract = {The mammalian neocortex is subdivided into cytoarchitectural areas with distinct connectivity, gene expression and neural functions. Areal identity is initially specified by rostrocaudal and mediolateral gene expression gradients in neuroepithelial and radial glial progenitors (the 'protomap'). On further differentiation, distinct sets of gene expression gradients arise in intermediate progenitors and postmitotic neurons, and are necessary to implement areal specification. However, it is still unknown whether postmitotic gene expression gradients can determine areal identity independently of protomap gradients. Here we show, by cell type-restricted genetic loss- and gain-of-function, that high levels of postmitotic COUP-TFI (Nr2f1) expression are necessary and sufficient for the development of sensory (caudal) areal identity. Our data indicate a crucial role for postmitotic patterning genes in areal specification and reveal an unexpected plasticity in this process, which may account for complex and evolutionarily novel structures characteristic of the mammalian neocortex.}, Author = {Alfano, C and Magrinelli, E and Harb, K and Hevner, R F and Studer, M}, Date-Added = {2018-01-16 21:04:33 +0000}, Date-Modified = {2018-01-16 21:04:33 +0000}, Doi = {10.1038/ncomms6632}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Mesh = {Animals; COUP Transcription Factor I; Female; Gene Expression Regulation, Developmental; Male; Mice; Mice, Knockout; Mitosis; Neocortex; Sensory Receptor Cells}, Month = {Dec}, Pages = {5632}, pmid = {25476200}, Pst = {epublish}, Title = {Postmitotic control of sensory area specification during neocortical development}, Volume = {5}, Year = {2014}, url = {papers/Alfano_NatCommun2014.pdf}} @article{Zembrzycki:2015, Abstract = {In mammals, the neocortical layout consists of few modality-specific primary sensory areas and a multitude of higher order ones. Abnormal layout of cortical areas may disrupt sensory function and behavior. Developmental genetic mechanisms specify primary areas, but mechanisms influencing higher order area properties are unknown. By exploiting gain-of and loss-of function mouse models of the transcription factor Emx2, we have generated bi-directional changes in primary visual cortex size in vivo and have used it as a model to show a novel and prominent function for genetic mechanisms regulating primary visual area size and also proportionally dictating the sizes of surrounding higher order visual areas. This finding redefines the role for intrinsic genetic mechanisms to concomitantly specify and scale primary and related higher order sensory areas in a linear fashion.}, Author = {Zembrzycki, Andreas and Stocker, Adam M and Leing{\"a}rtner, Axel and Sahara, Setsuko and Chou, Shen-Ju and Kalatsky, Valery and May, Scott R and Stryker, Michael P and O'Leary, Dennis Dm}, Date-Added = {2018-01-16 21:04:09 +0000}, Date-Modified = {2018-01-16 21:04:09 +0000}, Doi = {10.7554/eLife.11416}, Journal = {Elife}, Journal-Full = {eLife}, Keywords = {Emx2; brain evolution; developmental biology; extrastriate cortex; mouse; neocortical area patterning; neuroscience; sensory systems; stem cells; visual cortex}, Mesh = {Animals; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mice, Inbred C57BL; Mice, Transgenic; Transcription Factors; Vision, Ocular; Visual Cortex}, Month = {Dec}, Pmc = {PMC4739755}, pmid = {26705332}, Pst = {epublish}, Title = {Genetic mechanisms control the linear scaling between related cortical primary and higher order sensory areas}, Volume = {4}, Year = {2015}, url = {papers/Zembrzycki_Elife2015.pdf}} @article{Fenlon:2015b, Abstract = {BACKGROUND: Autism spectrum disorders (ASD) are a group of poorly understood behavioural disorders, which have increased in prevalence in the past two decades. Animal models offer the opportunity to understand the biological basis of these disorders. Studies comparing different mouse strains have identified the inbred BTBR T + tf/J (BTBR) strain as a mouse model of ASD based on its anti-social and repetitive behaviours. Adult BTBR mice have complete agenesis of the corpus callosum, reduced cortical thickness and changes in early neurogenesis. However, little is known about the development or ultimate organisation of cortical areas devoted to specific sensory and motor functions in these mice that may also contribute to their behavioural phenotype. RESULTS: In this study, we performed diffusion tensor imaging and tractography, together with histological analyses to investigate the emergence of functional areas in the cerebral cortex and their connections in BTBR mice and age-matched C57Bl/6 control mice. We found evidence that neither the anterior commissure nor the hippocampal commissure compensate for the loss of callosal connections, indicating that no interhemispheric neocortical connectivity is present in BTBR mice. We also found that both the primary visual and somatosensory cortical areas are shifted medially in BTBR mice compared to controls and that cortical thickness is differentially altered in BTBR mice between cortical areas and throughout development. CONCLUSIONS: We demonstrate that interhemispheric connectivity and cortical area formation are altered in an age- and region-specific manner in BTBR mice, which may contribute to the behavioural deficits previously observed in this strain. Some of these developmental patterns of change are also present in human ASD patients, and elucidating the aetiology driving cortical changes in BTBR mice may therefore help to increase our understanding of this disorder.}, Author = {Fenlon, Laura R and Liu, Sha and Gobius, Ilan and Kurniawan, Nyoman D and Murphy, Skyle and Moldrich, Randal X and Richards, Linda J}, Date-Added = {2018-01-16 21:03:53 +0000}, Date-Modified = {2018-01-16 21:03:53 +0000}, Doi = {10.1186/s13064-015-0033-y}, Journal = {Neural Dev}, Journal-Full = {Neural development}, Mesh = {Agenesis of Corpus Callosum; Aging; Animals; Anterior Cerebellar Commissure; Autism Spectrum Disorder; Cerebral Cortex; Diffusion Tensor Imaging; Disease Models, Animal; Fornix, Brain; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Neurologic Mutants; Phenotype; Somatosensory Cortex; Visual Cortex}, Month = {Apr}, Pages = {10}, Pmc = {PMC4412039}, pmid = {25879444}, Pst = {epublish}, Title = {Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder}, Volume = {10}, Year = {2015}, url = {papers/Fenlon_NeuralDev2015a.pdf}} @article{Barber:2016, Abstract = {Tangential migration is a mode of cell movement, which in the developing cerebral cortex, is defined by displacement parallel to the ventricular surface and orthogonal to the radial glial fibers. This mode of long-range migration is a strategy by which distinct neuronal classes generated from spatially and molecularly distinct origins can integrate to form appropriate neural circuits within the cortical plate. While it was previously believed that only GABAergic cortical interneurons migrate tangentially from their origins in the subpallial ganglionic eminences to integrate in the cortical plate, it is now known that transient populations of glutamatergic neurons also adopt this mode of migration. These include Cajal-Retzius cells (CRs), subplate neurons (SPs), and cortical plate transient neurons (CPTs), which have crucial roles in orchestrating the radial and tangential development of the embryonic cerebral cortex in a noncell-autonomous manner. While CRs have been extensively studied, it is only in the last decade that the molecular mechanisms governing their tangential migration have begun to be elucidated. To date, the mechanisms of SPs and CPTs tangential migration remain unknown. We therefore review the known signaling pathways, which regulate parameters of CRs migration including their motility, contact-redistribution and adhesion to the pial surface, and discuss this in the context of how CR migration may regulate their signaling activity in a spatial and temporal manner. {\copyright} 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 847-881, 2016.}, Author = {Barber, Melissa and Pierani, Alessandra}, Date-Added = {2018-01-16 21:03:39 +0000}, Date-Modified = {2018-01-16 21:03:39 +0000}, Doi = {10.1002/dneu.22363}, Journal = {Dev Neurobiol}, Journal-Full = {Developmental neurobiology}, Keywords = {Cajal-Retzius cells; cortical patterning; cortical plate transient neurons; glutamatergic neurons; subplate neurons; tangential migration}, Mesh = {Animals; Cell Movement; Cerebral Cortex; Humans; Neurons}, Month = {Aug}, Number = {8}, Pages = {847-81}, pmid = {26581033}, Pst = {ppublish}, Title = {Tangential migration of glutamatergic neurons and cortical patterning during development: Lessons from Cajal-Retzius cells}, Volume = {76}, Year = {2016}, url = {papers/Barber_DevNeurobiol2016.pdf}} @article{Vue:2013, Abstract = {The mammalian neocortex undergoes dramatic transformation during development, from a seemingly homogenous sheet of neuroepithelial cells into a complex structure that is tangentially divided into discrete areas. This process is thought to be controlled by a combination of intrinsic patterning mechanisms within the cortex and afferent axonal projections from the thalamus. However, roles of thalamic afferents in the formation of areas are still poorly understood. In this study, we show that genetically increasing or decreasing the size of the lateral geniculate nucleus of the mouse thalamus resulted in a corresponding change in the size of the primary visual area. Furthermore, elimination of most thalamocortical projections from the outset of their development resulted in altered areal gene expression patterns, particularly in the primary visual and somatosensory areas, where they lost sharp boundaries with adjacent areas. Together, these results demonstrate the critical roles of thalamic afferents in the establishment of neocortical areas.}, Author = {Vue, Tou Yia and Lee, Melody and Tan, Yew Ei and Werkhoven, Zachary and Wang, Lynn and Nakagawa, Yasushi}, Date-Added = {2018-01-16 21:03:03 +0000}, Date-Modified = {2018-01-16 21:03:03 +0000}, Doi = {10.1523/JNEUROSCI.5786-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Afferent Pathways; Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors; Cell Count; Cell Size; Embryo, Mammalian; Gene Expression Regulation, Developmental; Hedgehog Proteins; Homeodomain Proteins; Mice; Mice, Transgenic; Mutation; Neocortex; Proteins; RNA, Messenger; RNA, Untranslated; Thalamus}, Month = {May}, Number = {19}, Pages = {8442-53}, Pmc = {PMC3732791}, pmid = {23658181}, Pst = {ppublish}, Title = {Thalamic control of neocortical area formation in mice}, Volume = {33}, Year = {2013}, url = {papers/Vue_JNeurosci2013.pdf}} @article{Cholfin:2007, Abstract = {The frontal cortex (FC) is the seat of higher cognition. The genetic mechanisms that control formation of the functionally distinct subdivisions of the FC are unknown. Using a set of gene expression markers that distinguish subdivisions of the newborn mouse FC, we show that loss of Fgf17 selectively reduces the size of the dorsal FC whereas ventral/orbital FC appears normal. These changes are complemented by a rostral shift of sensory cortical areas. Thus, Fgf17 functions similar to Fgf8 in patterning the overall neocortical map but has a more selective role in regulating the properties of the dorsal but not ventral FC.}, Author = {Cholfin, Jeremy A and Rubenstein, John L R}, Date-Added = {2017-12-12 01:42:38 +0000}, Date-Modified = {2017-12-12 01:42:38 +0000}, Doi = {10.1073/pnas.0702225104}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Biomarkers; Body Patterning; Fibroblast Growth Factor 8; Fibroblast Growth Factors; Frontal Lobe; Gene Expression Regulation, Developmental; Mice; Mice, Knockout; Mutation}, Month = {May}, Number = {18}, Pages = {7652-7}, Pmc = {PMC1863435}, pmid = {17442747}, Pst = {ppublish}, Title = {Patterning of frontal cortex subdivisions by Fgf17}, Volume = {104}, Year = {2007}, url = {papers/Cholfin_ProcNatlAcadSciUSA2007.pdf}} @article{Cederquist:2013, Abstract = {The mammalian neocortex is parcellated into anatomically and functionally distinct areas. The establishment of area-specific neuronal diversity and circuit connectivity enables distinct neocortical regions to control diverse and specialized functional outputs, yet underlying molecular controls remain largely unknown. Here, we identify a central role for the transcriptional regulator Lim-only 4 (Lmo4) in establishing the diversity of neuronal subtypes within rostral mouse motor cortex, where projection neurons have particularly diverse and multi-projection connectivity compared with caudal motor cortex. In rostral motor cortex, we report that both subcerebral projection neurons (SCPN), which send projections away from the cerebrum, and callosal projection neurons (CPN), which send projections to contralateral cortex, express Lmo4, whereas more caudal SCPN and CPN do not. Lmo4-expressing SCPN and CPN populations are comprised of multiple hodologically distinct subtypes. SCPN in rostral layer Va project largely to brainstem, whereas SCPN in layer Vb project largely to spinal cord, and a subset of both rostral SCPN and CPN sends second ipsilateral caudal (backward) projections in addition to primary projections. Without Lmo4 function, the molecular identity of neurons in rostral motor cortex is disrupted and more homogenous, rostral layer Va SCPN aberrantly project to the spinal cord, and many dual-projection SCPN and CPN fail to send a second backward projection. These molecular and hodological disruptions result in greater overall homogeneity of motor cortex output. Together, these results identify Lmo4 as a central developmental control over the diversity of motor cortex projection neuron subpopulations, establishing their area-specific identity and specialized connectivity.}, Author = {Cederquist, Gustav Y and Azim, Eiman and Shnider, Sara J and Padmanabhan, Hari and Macklis, Jeffrey D}, Date-Added = {2017-12-12 01:38:13 +0000}, Date-Modified = {2017-12-12 01:38:13 +0000}, Doi = {10.1523/JNEUROSCI.5140-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Adaptor Proteins, Signal Transducing; Animals; Brain Stem; Corpus Callosum; Female; Gene Expression Regulation; LIM Domain Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Cortex; Neural Pathways; Neurons; Spinal Cord}, Month = {Apr}, Number = {15}, Pages = {6321-32}, Pmc = {PMC3698850}, pmid = {23575831}, Pst = {ppublish}, Title = {Lmo4 establishes rostral motor cortex projection neuron subtype diversity}, Volume = {33}, Year = {2013}, url = {papers/Cederquist_JNeurosci2013.pdf}} @article{Subramanian:2009, Abstract = {The early cortical primordium develops from a sheet of neuroepithelium that is flanked by distinct signaling centers. Of these, the hem and the antihem are positioned as longitudinal stripes, running rostro-caudally along the medial and lateral faces, respectively, of each telencepahlic hemisphere. In this review we examine the similarities and differences in how these two signaling centers arise, their roles in patterning adjacent tissues, and the cells and structures they contribute to. Since both the hem and the antihem have been identified across many vertebrate phyla, they appear to be part of an evolutionary conserved set of mechanisms that play fundamental roles in forebrain development.}, Author = {Subramanian, Lakshmi and Remedios, Ryan and Shetty, Ashwin and Tole, Shubha}, Date-Added = {2017-12-11 23:58:12 +0000}, Date-Modified = {2017-12-11 23:58:12 +0000}, Doi = {10.1016/j.semcdb.2009.04.001}, Journal = {Semin Cell Dev Biol}, Journal-Full = {Seminars in cell \& developmental biology}, Mesh = {Animals; Biological Evolution; Homeodomain Proteins; Telencephalon; Transcription Factors; Wnt Proteins}, Month = {Aug}, Number = {6}, Pages = {712-8}, Pmc = {PMC2791850}, pmid = {19446478}, Pst = {ppublish}, Title = {Signals from the edges: the cortical hem and antihem in telencephalic development}, Volume = {20}, Year = {2009}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.semcdb.2009.04.001}} @article{Caronia-Brown:2014, Abstract = {The cortical hem, a source of Wingless-related (WNT) and bone morphogenetic protein (BMP) signaling in the dorsomedial telencephalon, is the embryonic organizer for the hippocampus. Whether the hem is a major regulator of cortical patterning outside the hippocampus has not been investigated. We examined regional organization across the entire cerebral cortex in mice genetically engineered to lack the hem. Indicating that the hem regulates dorsoventral patterning in the cortical hemisphere, the neocortex, particularly dorsomedial neocortex, was reduced in size in late-stage hem-ablated embryos, whereas cortex ventrolateral to the neocortex expanded dorsally. Unexpectedly, hem ablation also perturbed regional patterning along the rostrocaudal axis of neocortex. Rostral neocortical domains identified by characteristic gene expression were expanded, and caudal domains diminished. A similar shift occurs when fibroblast growth factor (FGF) 8 is increased at the rostral telencephalic organizer, yet the FGF8 source was unchanged in hem-ablated brains. Rather we found that hem WNT or BMP signals, or both, have opposite effects to those of FGF8 in regulating transcription factors that control the size and position of neocortical areas. When the hem is ablated a necessary balance is perturbed, and cerebral cortex is rostralized. Our findings reveal a much broader role for the hem in cortical development than previously recognized, and emphasize that two major signaling centers interact antagonistically to pattern cerebral cortex.}, Author = {Caronia-Brown, Giuliana and Yoshida, Michio and Gulden, Forrest and Assimacopoulos, Stavroula and Grove, Elizabeth A}, Date-Added = {2017-12-11 23:51:36 +0000}, Date-Modified = {2017-12-11 23:51:36 +0000}, Doi = {10.1242/dev.106914}, Journal = {Development}, Journal-Full = {Development (Cambridge, England)}, Keywords = {Embryonic patterning; Fgf8; Mouse; Neocortex; Signaling center; Wnt3a}, Mesh = {Animals; Body Patterning; Bone Morphogenetic Proteins; Cell Proliferation; Female; Fibroblast Growth Factor 8; Gene Deletion; Gene Expression Regulation, Developmental; Hippocampus; Mice; Neocortex; Organ Size; Organizers, Embryonic; Phenotype; Signal Transduction; Stem Cells; Wnt Proteins}, Month = {Jul}, Number = {14}, Pages = {2855-65}, Pmc = {PMC4197624}, pmid = {24948604}, Pst = {ppublish}, Title = {The cortical hem regulates the size and patterning of neocortex}, Volume = {141}, Year = {2014}, url = {papers/Caronia-Brown_Development2014.pdf}} @article{Puelles:2003, Abstract = {The prosomeric model attributes morphological meaning to gene expression patterns and other data in the forebrain. It divides this territory into the same transverse segments (prosomeres) and longitudinal zones in all vertebrates. The axis and longitudinal zones of this model are widely accepted but controversy subsists about the number of prosomeres and their nature as segments. We describe difficulties encountered in establishing continuity between prosomeric limits postulated in the hypothalamus and intra-telencephalic limits. Such difficulties throw doubt on the intersegmental nature of these limits. We sketch a simplified model, in which the secondary prosencephalon (telencephalon plus hypothalamus) is a complex protosegment not subdivided into prosomeres, which exhibits patterning singularities. By contrast, we continue to postulate that prosomeres p1-p3 (i.e. the pretectum, thalamus and prethalamus) are the caudal forebrain.}, Author = {Puelles, Luis and Rubenstein, John L R}, Date-Added = {2017-12-11 23:48:40 +0000}, Date-Modified = {2017-12-11 23:48:40 +0000}, Doi = {10.1016/S0166-2236(03)00234-0}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Mesh = {Animals; Gene Expression; Humans; Hypothalamus; Models, Neurological; Prosencephalon; Telencephalon}, Month = {Sep}, Number = {9}, Pages = {469-76}, pmid = {12948657}, Pst = {ppublish}, Title = {Forebrain gene expression domains and the evolving prosomeric model}, Volume = {26}, Year = {2003}, url = {papers/Puelles_TrendsNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0166-2236(03)00234-0}} @article{OLeary:2008, Abstract = {Arealization of the neocortex is controlled by a regulatory hierarchy beginning with morphogens secreted from patterning centers positioned at the perimeter of the dorsal telencephalon. These morphogens act in part to establish within cortical progenitors the differential expression of transcription factors that specify their area identity, which is inherited by their neuronal progeny, providing the genetic framework for area patterning. The two patterning centers most directly implicated in arealization are the commissural plate, which expresses fibroblast growth factors, and the cortical hem, which expresses bone morphogenetic proteins and vertebrate orthologs of Drosophila wingless, the Wnts. A third, albeit putative, patterning center is the antihem, identified by its expression of multiple signaling molecules. We describe recent findings on roles for these patterning centers in arealization. We also present the most recent evidence on functions of the four transcription factors, Emx2, COUP-TFI, Pax6, and Sp8, thus far implicated in arealization. We also describe screens for candidate target genes of these transcription factors, or other genes potentially involved in arealization. We conclude with an assessment of a forward genetics approach for identifying genes involved in determining area size based in part on quantitative trait locus mapping, and the implications for significant differences between individuals in area size on behavioral performance.}, Author = {O'Leary, Dennis Dm and Sahara, Setsuko}, Date-Added = {2017-12-11 22:37:47 +0000}, Date-Modified = {2017-12-11 22:37:47 +0000}, Doi = {10.1016/j.conb.2008.05.011}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Mesh = {Animals; Body Patterning; Gene Expression Regulation, Developmental; Genetic Variation; Intercellular Signaling Peptides and Proteins; Morphogenesis; Neocortex; Signal Transduction; Telencephalon; Transcription Factors}, Month = {Feb}, Number = {1}, Pages = {90-100}, Pmc = {PMC2677555}, pmid = {18524571}, Pst = {ppublish}, Title = {Genetic regulation of arealization of the neocortex}, Volume = {18}, Year = {2008}, url = {papers/O'Leary_CurrOpinNeurobiol2008.pdf}} @article{Hammock:2013, Abstract = {UNLABELLED: Oxytocin (OXT) has drawn increasing attention as a developmentally relevant neuropeptide given its role in the brain regulation of social behavior. It has been suggested that OXT plays an important role in the infant brain during caregiver attachment in nurturing familial contexts, but there is incomplete experimental evidence. Mouse models of OXT system genes have been particularly informative for the role of the OXT system in social behavior, however, the developing brain areas that could respond to ligand activation of the OXT receptor (OXTR) have yet to be identified in this species. Here we report new data revealing dynamic ligand-binding distribution of OXTR in the developing mouse brain. Using male and female C57BL/6J mice at postnatal days (P) 0, 7, 14, 21, 35, and 60 we quantified OXTR ligand binding in several brain areas which changed across development. Further, we describe OXTR ligand binding in select tissues of the near-term whole embryo at E18.5. Together, these data aid in the interpretation of findings in mouse models of the OXT system and generate new testable hypotheses for developmental roles for OXT in mammalian systems. We discuss our findings in the context of developmental disorders (including autism), attachment biology, and infant physiological regulation. SUMMARY: Quantitative mapping of selective OXTR ligand binding during postnatal development in the mouse reveals an unexpected, transient expression in layers II/III throughout the mouse neocortex. OXTR are also identified in several tissues in the whole late embryo, including the adrenal glands, brown adipose tissue, and the oronasal cavity.}, Author = {Hammock, Elizabeth A D and Levitt, Pat}, Date-Added = {2017-12-09 14:28:14 +0000}, Date-Modified = {2017-12-09 14:28:14 +0000}, Doi = {10.3389/fnbeh.2013.00195}, Journal = {Front Behav Neurosci}, Journal-Full = {Frontiers in behavioral neuroscience}, Keywords = {adrenal gland; autism; autoradiography; experience-dependent plasticity; kidney; neocortex; oronasal cavity; oxytocin}, Pages = {195}, Pmc = {PMC3858721}, pmid = {24376405}, Pst = {epublish}, Title = {Oxytocin receptor ligand binding in embryonic tissue and postnatal brain development of the C57BL/6J mouse}, Volume = {7}, Year = {2013}, url = {papers/Hammock_FrontBehavNeurosci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fnbeh.2013.00195}} @article{Ryden:1969, Abstract = {Using tritium-labelled oxytocin with a high specific activity, the halflife in the blood and the urinary excretion of intravenously injected oxytocin were followed in the female. The following groups of patients were studied: normally menstruating women during different phases of the menstrual cycle, women using a combination of gestagenic and oestrogenic hormones for oral contraception, and pregnant women in the first and second trimester. The pregnant women were admitted to the hospital for legal abortion in the 10th--20th week of gestation. In the proliferative phase, t½ was 272 seconds (n = 14), in the secretory phase 221 seconds (n = 5), and in women using oral contraceptives 199 seconds (n = 10). In pregnant women during the first trimester, t½ was 178 seconds (n = 6). The corresponding value in women examined during the 14th--17th weeks and during the 18th--20th weeks of gestation was 295 seconds (n = 6) and 282 seconds (n = 6), respectively. T½ was also determined within 24 h of abortion in patients in the second trimester, where the abortion was induced by intra-amniotic instillation of 50% glucose. In all cases a decrease in t½ was found. The decrease was most marked in women during the 18th--20th weeks of gestation. Altogether 25--50% of the radioactivity injected was recovered in the urine from pregnant women within 3 h of the injection. Thin-layer chromatography of the urine did not reveal the presence of any intact oxytocin. The results demonstrate that the disappearance of oxytocin from the blood seems to be influenced by the sex hormones. Thus, an oestrogendominated stage shows a lower disappearance rate, whereas gestagens produce the reverse effect. The pronounced decrease in t½ in pregnant women immediately after abortion might be due to a change to a more progesterone-dominated stage induced by the death of the foetus, or by an alteration in the affinity of oxytocin to the myometrium. }, Author = {Ryd{\'e}n, G and Sj{\"o}holm, I}, Date-Added = {2017-12-09 14:26:15 +0000}, Date-Modified = {2017-12-09 14:27:00 +0000}, Journal = {Acta Endocrinol (Copenh)}, Journal-Full = {Acta endocrinologica}, Mesh = {Abortion, Legal; Chromatography, Thin Layer; Contraceptives, Oral; Female; Gestational Age; Humans; Oxytocin; Pregnancy; Tritium}, Month = {Jul}, Number = {3}, Pages = {425-31}, pmid = {5820054}, Pst = {ppublish}, Title = {Half-life of oxytocin in blood of pregnant and non-pregnant women}, Volume = {61}, Year = {1969}} @article{Greenwood:2017, Abstract = {Oxytocin (OXT) is a pleiotropic regulator of physiology and behavior. An emerging body of evidence demonstrates a role for OXT in the transition to postnatal life of the infant. To identify potential sites of OXT action via the OXT receptor (OXTR) in the newborn mouse, we performed receptor autoradiography on 20 μm sagittal sections of whole postnatal day 0 male and female mice on a C57BL/6J background using the 125iodinated ornithine vasotocin analog ([125I]-OVTA) radioligand. A competitive binding assay on both wild-type (WT) and OXTR knockout (OXTR KO) tissue was used to assess the selectivity of [125I]-OVTA for neonatal OXTR. Radioactive ligand (0.05 nM [125I]-OVTA) was competed against concentrations of 0 nM, 10 nM, and 1000 nM excess unlabeled OXT. Autoradiographs demonstrated the high selectivity of the radioligand for infant peripheral OXTR. Specific ligand binding activity for OXTR was observed in the oronasal cavity, the eye, whisker pads, adrenal gland, and anogenital region in the neonatal OXTR WT mouse, but was absent in neonatal OXTR KO. Nonspecific binding was observed in areas with a high lipid content such as the scapular brown adipose tissue and the liver: in these regions, binding was present in both OXTR WT and KO mice, and could not be competed away with OXT in either WT or KO mice. Collectively, these data confirm novel OXT targets in the periphery of the neonate. These peripheral OXTR sites, coupled with the immaturity of the neonate's own OXT system, suggest a role for exogenous OXT in modulating peripheral physiology and development.}, Author = {Greenwood, Maria A and Hammock, Elizabeth A D}, Date-Added = {2017-12-09 04:27:42 +0000}, Date-Modified = {2017-12-09 04:27:42 +0000}, Doi = {10.1371/journal.pone.0172904}, Journal = {PLoS One}, Journal-Full = {PloS one}, Mesh = {Adipose Tissue, Brown; Adrenal Glands; Animals; Animals, Newborn; Binding Sites; Eye; Female; Liver; Male; Mice, Inbred C57BL; Organ Specificity; Oxytocin; Periodontium; Protein Binding; Receptors, Oxytocin; Tooth; Vibrissae}, Number = {2}, Pages = {e0172904}, Pmc = {PMC5325587}, pmid = {28235051}, Pst = {epublish}, Title = {Oxytocin receptor binding sites in the periphery of the neonatal mouse}, Volume = {12}, Year = {2017}, url = {papers/Greenwood_PLoSOne2017.pdf}} @article{Khodagholy:2017, Abstract = {Consolidation of declarative memories requires hippocampal-neocortical communication. Although experimental evidence supports the role of sharp-wave ripples in transferring hippocampal information to the neocortex, the exact cortical destinations and the physiological mechanisms of such transfer are not known. We used a conducting polymer-based conformable microelectrode array (NeuroGrid) to record local field potentials and neural spiking across the dorsal cortical surface of the rat brain, combined with silicon probe recordings in the hippocampus, to identify candidate physiological patterns. Parietal, midline, and prefrontal, but not primary cortical areas, displayed localized ripple (100 to 150 hertz) oscillations during sleep, concurrent with hippocampal ripples. Coupling between hippocampal and neocortical ripples was strengthened during sleep following learning. These findings suggest that ripple-ripple coupling supports hippocampal-association cortical transfer of memory traces.}, Author = {Khodagholy, Dion and Gelinas, Jennifer N and Buzs{\'a}ki, Gy{\"o}rgy}, Date-Added = {2017-11-16 17:44:39 +0000}, Date-Modified = {2017-11-16 17:44:39 +0000}, Doi = {10.1126/science.aan6203}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Month = {10}, Number = {6361}, Pages = {369-372}, pmid = {29051381}, Pst = {ppublish}, Title = {Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus}, Volume = {358}, Year = {2017}, url = {papers/Khodagholy_Science2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.aan6203}} @article{Cherry:2017, Abstract = {CCL11, a protein previously associated with age-associated cognitive decline, is observed to be increased in the brain and cerebrospinal fluid (CSF) in chronic traumatic encephalopathy (CTE) compared to Alzheimer's disease (AD). Using a cohort of 23 deceased American football players with neuropathologically verified CTE, 50 subjects with neuropathologically diagnosed AD, and 18 non-athlete controls, CCL11 was measured with ELISA in the dorsolateral frontal cortex (DLFC) and CSF. CCL11 levels were significantly increased in the DLFC in subjects with CTE (fold change = 1.234, p < 0.050) compared to non-athlete controls and AD subjects with out a history of head trauma. This increase was also seen to correlate with years of exposure to American football (β = 0.426, p = 0.048) independent of age (β = -0.046, p = 0.824). Preliminary analyses of a subset of subjects with available post-mortem CSF showed a trend for increased CCL11 among individuals with CTE (p = 0.069) mirroring the increase in the DLFC. Furthermore, an association between CSF CCL11 levels and the number of years exposed to football (β = 0.685, p = 0.040) was observed independent of age (β = -0.103, p = 0.716). Finally, a receiver operating characteristic (ROC) curve analysis demonstrated CSF CCL11 accurately distinguished CTE subjects from non-athlete controls and AD subjects (AUC = 0.839, 95% CI 0.62-1.058, p = 0.028). Overall, the current findings provide preliminary evidence that CCL11 may be a novel target for future CTE biomarker studies.}, Author = {Cherry, Jonathan D and Stein, Thor D and Tripodis, Yorghos and Alvarez, Victor E and Huber, Bertrand R and Au, Rhoda and Kiernan, Patrick T and Daneshvar, Daniel H and Mez, Jesse and Solomon, Todd M and Alosco, Michael L and McKee, Ann C}, Date-Added = {2017-11-14 21:44:33 +0000}, Date-Modified = {2017-11-14 21:46:24 +0000}, Doi = {10.1371/journal.pone.0185541}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {concussion}, Mesh = {Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Brain; Chemokine CCL11; Chronic Traumatic Encephalopathy; Female; Football; Humans; Male; Middle Aged}, Number = {9}, Pages = {e0185541}, Pmc = {PMC5614644}, pmid = {28950005}, Pst = {epublish}, Title = {CCL11 is increased in the CNS in chronic traumatic encephalopathy but not in Alzheimer's disease}, Volume = {12}, Year = {2017}, url = {papers/Cherry_PLoSOne2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0185541}} @article{Ojo:2016, Abstract = {Chronic traumatic encephalopathy (CTE) is a neurological and psychiatric condition marked by preferential perivascular foci of neurofibrillary and glial tangles (composed of hyperphosphorylated-tau proteins) in the depths of the sulci. Recent retrospective case series published over the last decade on athletes and military personnel have added considerably to our clinical and histopathological knowledge of CTE. This has marked a vital turning point in the traumatic brain injury (TBI) field, raising public awareness of the potential long-term effects of mild and moderate repetitive TBI, which has been recognized as one of the major risk factors associated with CTE. Although these human studies have been informative, their retrospective design carries certain inherent limitations that should be cautiously interpreted. In particular, the current overriding issue in the CTE literature remains confusing in regard to appropriate definitions of terminology, variability in individual pathologies and the potential case selection bias in autopsy based studies. There are currently no epidemiological or prospective studies on CTE. Controlled preclinical studies in animals therefore provide an alternative means for specifically interrogating aspects of CTE pathogenesis. In this article, we review the current literature and discuss difficulties and challenges of developing in-vivo TBI experimental paradigms to explore the link between repetitive head trauma and tau-dependent changes. We provide our current opinion list of recommended features to consider for successfully modeling CTE in animals to better understand the pathobiology and develop therapeutics and diagnostics, and critical factors, which might influence outcome. We finally discuss the possible directions of future experimental research in the repetitive TBI/CTE field.}, Author = {Ojo, Joseph O and Mouzon, Benoit C and Crawford, Fiona}, Date-Added = {2017-11-14 21:43:20 +0000}, Date-Modified = {2017-11-14 21:46:24 +0000}, Doi = {10.1016/j.expneurol.2015.06.003}, Journal = {Exp Neurol}, Journal-Full = {Experimental neurology}, Keywords = {Animal models; Astroglial tangles; CTE; Concussion; Neurobehaviour; Neurofibrillary tangles; Neuropathology; Repetitive TBI; Tau; Transgenic mice; concussion}, Mesh = {Animals; Brain Injury, Chronic; Craniocerebral Trauma; Disease Models, Animal; Humans; Mice; Translational Medical Research; tau Proteins}, Month = {Jan}, Pages = {389-404}, pmid = {26054886}, Pst = {ppublish}, Title = {Repetitive head trauma, chronic traumatic encephalopathy and tau: Challenges in translating from mice to men}, Volume = {275 Pt 3}, Year = {2016}, url = {papers/Ojo_ExpNeurol2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2015.06.003}} @article{McKee:2013, Abstract = {Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.}, Author = {McKee, Ann C and Stern, Robert A and Nowinski, Christopher J and Stein, Thor D and Alvarez, Victor E and Daneshvar, Daniel H and Lee, Hyo-Soon and Wojtowicz, Sydney M and Hall, Garth and Baugh, Christine M and Riley, David O and Kubilus, Caroline A and Cormier, Kerry A and Jacobs, Matthew A and Martin, Brett R and Abraham, Carmela R and Ikezu, Tsuneya and Reichard, Robert Ross and Wolozin, Benjamin L and Budson, Andrew E and Goldstein, Lee E and Kowall, Neil W and Cantu, Robert C}, Date-Added = {2017-11-14 21:41:39 +0000}, Date-Modified = {2017-11-14 21:46:24 +0000}, Doi = {10.1093/brain/aws307}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {concussion}, Mesh = {Adolescent; Adult; Aged; Aged, 80 and over; Athletes; Brain; Brain Injury, Chronic; Disease Progression; Football; Humans; Male; Middle Aged; Neurofibrillary Tangles; Tauopathies; Veterans; tau Proteins}, Month = {Jan}, Number = {Pt 1}, Pages = {43-64}, Pmc = {PMC3624697}, pmid = {23208308}, Pst = {ppublish}, Title = {The spectrum of disease in chronic traumatic encephalopathy}, Volume = {136}, Year = {2013}, url = {papers/McKee_Brain2013.pdf}} @article{Smith:2013a, Abstract = {Traumatic brain injury (TBI) has long been recognized to be a risk factor for dementia. This association has, however, only recently gained widespread attention through the increased awareness of 'chronic traumatic encephalopathy' (CTE) in athletes exposed to repetitive head injury. Originally termed 'dementia pugilistica' and linked to a career in boxing, descriptions of the neuropathological features of CTE include brain atrophy, cavum septum pellucidum, and amyloid-β, tau and TDP-43 pathologies, many of which might contribute to clinical syndromes of cognitive impairment. Similar chronic pathologies are also commonly found years after just a single moderate to severe TBI. However, little consensus currently exists on specific features of these post-TBI syndromes that might permit their confident clinical and/or pathological diagnosis. Moreover, the mechanisms contributing to neurodegeneration following TBI largely remain unknown. Here, we review the current literature and controversies in the study of chronic neuropathological changes after TBI.}, Author = {Smith, Douglas H and Johnson, Victoria E and Stewart, William}, Date-Added = {2017-11-14 21:40:36 +0000}, Date-Modified = {2017-11-14 21:46:24 +0000}, Doi = {10.1038/nrneurol.2013.29}, Journal = {Nat Rev Neurol}, Journal-Full = {Nature reviews. Neurology}, Keywords = {concussion}, Mesh = {Aged; Athletic Injuries; Brain; Brain Injuries; Chronic Disease; Dementia; Disease Progression; Humans; Male; Neurofibrillary Tangles; Risk Factors; Young Adult}, Month = {Apr}, Number = {4}, Pages = {211-21}, Pmc = {PMC4513655}, pmid = {23458973}, Pst = {ppublish}, Title = {Chronic neuropathologies of single and repetitive TBI: substrates of dementia?}, Volume = {9}, Year = {2013}, url = {papers/Smith_NatRevNeurol2013.pdf}} @article{Hay:2016, Abstract = {Almost a century ago, the first clinical account of the punch-drunk syndrome emerged, describing chronic neurological and neuropsychiatric sequelae occurring in former boxers. Thereafter, throughout the twentieth century, further reports added to our understanding of the neuropathological consequences of a career in boxing, leading to descriptions of a distinct neurodegenerative pathology, termed dementia pugilistica. During the past decade, growing recognition of this pathology in autopsy studies of nonboxers who were exposed to repetitive, mild traumatic brain injury, or to a single, moderate or severe traumatic brain injury, has led to an awareness that it is exposure to traumatic brain injury that carries with it a risk of this neurodegenerative disease, not the sport or the circumstance in which the injury is sustained. Furthermore, the neuropathology of the neurodegeneration that occurs after traumatic brain injury, now termed chronic traumatic encephalopathy, is acknowledged as being a complex, mixed, but distinctive pathology, the detail of which is reviewed in this article.}, Author = {Hay, Jennifer and Johnson, Victoria E and Smith, Douglas H and Stewart, William}, Date-Added = {2017-11-14 21:39:50 +0000}, Date-Modified = {2017-11-14 21:46:24 +0000}, Doi = {10.1146/annurev-pathol-012615-044116}, Journal = {Annu Rev Pathol}, Journal-Full = {Annual review of pathology}, Keywords = {CTE; amyloid; axons; neurodegeneration; tau; traumatic brain injury; concussion}, Mesh = {Animals; Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Humans}, Month = {May}, Pages = {21-45}, Pmc = {PMC5367053}, pmid = {26772317}, Pst = {ppublish}, Title = {Chronic Traumatic Encephalopathy: The Neuropathological Legacy of Traumatic Brain Injury}, Volume = {11}, Year = {2016}, url = {papers/Hay_AnnuRevPathol2016.pdf}} @article{Montenigro:2015, Abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that is most often identified in postmortem autopsies of individuals exposed to repetitive head impacts, such as boxers and football players. The neuropathology of CTE is characterized by the accumulation of hyperphosphorylated tau protein in a pattern that is unique from that of other neurodegenerative diseases, including Alzheimer's disease. The clinical features of CTE are often progressive, leading to dramatic changes in mood, behavior, and cognition, frequently resulting in debilitating dementia. In some cases, motor features, including parkinsonism, can also be present. In this review, the historical origins of CTE are revealed and an overview of the current state of knowledge of CTE is provided, including the neuropathology, clinical features, proposed clinical and pathological diagnostic criteria, potential in vivo biomarkers, known risk factors, and treatment options.}, Author = {Montenigro, Philip H and Corp, Daniel T and Stein, Thor D and Cantu, Robert C and Stern, Robert A}, Date-Added = {2017-11-14 21:39:33 +0000}, Date-Modified = {2017-11-14 21:46:24 +0000}, Doi = {10.1146/annurev-clinpsy-032814-112814}, Journal = {Annu Rev Clin Psychol}, Journal-Full = {Annual review of clinical psychology}, Keywords = {chronic traumatic encephalopathy; concussion; football; history; neurodegenerative disorders; traumatic brain injury; concussion}, Mesh = {Biomarkers; Boxing; Brain; Brain Injury, Chronic; Football; History, 20th Century; History, 21st Century; Humans; Neuroimaging; Risk Factors}, Pages = {309-30}, pmid = {25581233}, Pst = {ppublish}, Title = {Chronic traumatic encephalopathy: historical origins and current perspective}, Volume = {11}, Year = {2015}, url = {papers/Montenigro_AnnuRevClinPsychol2015.pdf}} @article{McKee:2016, Abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegeneration characterized by the abnormal accumulation of hyperphosphorylated tau protein within the brain. Like many other neurodegenerative conditions, at present, CTE can only be definitively diagnosed by post-mortem examination of brain tissue. As the first part of a series of consensus panels funded by the NINDS/NIBIB to define the neuropathological criteria for CTE, preliminary neuropathological criteria were used by 7 neuropathologists to blindly evaluate 25 cases of various tauopathies, including CTE, Alzheimer's disease, progressive supranuclear palsy, argyrophilic grain disease, corticobasal degeneration, primary age-related tauopathy, and parkinsonism dementia complex of Guam. The results demonstrated that there was good agreement among the neuropathologists who reviewed the cases (Cohen's kappa, 0.67) and even better agreement between reviewers and the diagnosis of CTE (Cohen's kappa, 0.78). Based on these results, the panel defined the pathognomonic lesion of CTE as an accumulation of abnormal hyperphosphorylated tau (p-tau) in neurons and astroglia distributed around small blood vessels at the depths of cortical sulci and in an irregular pattern. The group also defined supportive but non-specific p-tau-immunoreactive features of CTE as: pretangles and NFTs affecting superficial layers (layers II-III) of cerebral cortex; pretangles, NFTs or extracellular tangles in CA2 and pretangles and proximal dendritic swellings in CA4 of the hippocampus; neuronal and astrocytic aggregates in subcortical nuclei; thorn-shaped astrocytes at the glial limitans of the subpial and periventricular regions; and large grain-like and dot-like structures. Supportive non-p-tau pathologies include TDP-43 immunoreactive neuronal cytoplasmic inclusions and dot-like structures in the hippocampus, anteromedial temporal cortex and amygdala. The panel also recommended a minimum blocking and staining scheme for pathological evaluation and made recommendations for future study. This study provides the first step towards the development of validated neuropathological criteria for CTE and will pave the way towards future clinical and mechanistic studies.}, Author = {McKee, Ann C and Cairns, Nigel J and Dickson, Dennis W and Folkerth, Rebecca D and Keene, C Dirk and Litvan, Irene and Perl, Daniel P and Stein, Thor D and Vonsattel, Jean-Paul and Stewart, William and Tripodis, Yorghos and Crary, John F and Bieniek, Kevin F and Dams-O'Connor, Kristen and Alvarez, Victor E and Gordon, Wayne A and {TBI/CTE group}}, Date-Added = {2017-11-14 21:38:47 +0000}, Date-Modified = {2017-11-14 21:46:24 +0000}, Doi = {10.1007/s00401-015-1515-z}, Journal = {Acta Neuropathol}, Journal-Full = {Acta neuropathologica}, Keywords = {Brain trauma; Chronic traumatic encephalopathy; Neurodegenerative disorders; Tauopathy; Traumatic brain injury; concussion}, Mesh = {Alzheimer Disease; Autopsy; Brain Injury, Chronic; Humans; National Institute of Biomedical Imaging and Bioengineering (U.S.); National Institute of Neurological Disorders and Stroke; Neurofibrillary Tangles; Neurons; Tauopathies; United States; tau Proteins}, Month = {Jan}, Number = {1}, Pages = {75-86}, Pmc = {PMC4698281}, pmid = {26667418}, Pst = {ppublish}, Title = {The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy}, Volume = {131}, Year = {2016}, url = {papers/McKee_ActaNeuropathol2016.pdf}} @article{Yagita:2005, Abstract = {We have generated 362 bp and 547 bp partial sequences for Rana pipiens ephrin-A2 and ephrin-A5 mRNA, respectively. Translation homologies for the comparable segments of cDNA of chicken, mouse and human are 90.8, 86.9 and 84.4% for the ephrin-A2 sequence and 85.7, 85.0 and 85.0% for the ephrin-A5 sequence. Digoxigenin-labeled riboprobes were prepared and applied by means of in situ hybridization to whole-mounts of the brains of mature adults and expression patterns in tadpoles were also explored. The RNA probes revealed similar posterior (high) to anterior (low) expression gradients in the adult tectum, demonstrating that both ephrin-As are expressed in the adult Ranid frog tectum. Only the ephrin-A2 probe was tested on tadpole brain, yielding an appropriately graded expression pattern similar to the adult.}, Author = {Yagita, Yoshiki and Barjis, Isaac and Hecht, Michael and Bach, Helene and Feldheim, David A and Scalia, Frank}, Date-Added = {2017-11-01 21:08:33 +0000}, Date-Modified = {2017-11-01 21:08:33 +0000}, Doi = {10.1016/j.devbrainres.2005.06.016}, Journal = {Brain Res Dev Brain Res}, Journal-Full = {Brain research. Developmental brain research}, Mesh = {Animals; Chickens; Conserved Sequence; DNA, Complementary; Ephrin-A2; Ephrin-A5; Evolution, Molecular; Gene Expression Regulation, Developmental; Humans; Larva; Mice; Molecular Sequence Data; Nucleotides; RNA, Messenger; Rana pipiens; Sequence Homology, Amino Acid; Sequence Homology, Nucleic Acid; Superior Colliculi}, Month = {Sep}, Number = {1}, Pages = {72-7}, pmid = {16083970}, Pst = {ppublish}, Title = {Partial nucleotide sequences and expression patterns of frog (Rana pipiens) ephrin-A2 and ephrin-A5 mRNA}, Volume = {159}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devbrainres.2005.06.016}} @article{Kramer:2004, Abstract = {This paper describes a simple method for the preparation and characterization of protein density gradients on solid supports. The method employs colloidal metal nanoparticles as protein carriers and optical tags and is capable of forming linear, exponential, 1D, 2D, and multiprotein gradients of varying slope without expensive or sophisticated surface patterning techniques. Surfaces patterned with proteins using the procedures described within are shown to support cell growth and are thus suitable for studies of protein-cell interactions.}, Author = {Kr{\"a}mer, Stephan and Xie, Huan and Gaff, John and Williamson, John R and Tkachenko, Alexander G and Nouri, Navid and Feldheim, David A and Feldheim, Daniel L}, Date-Added = {2017-11-01 21:08:22 +0000}, Date-Modified = {2017-11-01 21:08:22 +0000}, Doi = {10.1021/ja031674n}, Journal = {J Am Chem Soc}, Journal-Full = {Journal of the American Chemical Society}, Mesh = {Animals; Axons; Cattle; Cell Division; Cells, Cultured; Chromatography, High Pressure Liquid; Gold Colloid; Hippocampus; Metals; Microscopy, Fluorescence; Nanotechnology; Neurons; Polylysine; Rats; Serum Albumin, Bovine; Spectrophotometry}, Month = {May}, Number = {17}, Pages = {5388-95}, pmid = {15113210}, Pst = {ppublish}, Title = {Preparation of protein gradients through the controlled deposition of protein-nanoparticle conjugates onto functionalized surfaces}, Volume = {126}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1021/ja031674n}} @article{Jiao:2008, Abstract = {In the central nervous system (CNS) of adult mammals, neurogenesis occurs in only two restricted areas, the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ). Isolation of multipotent progenitor cells from other CNS regions suggests that their neurogenic potential is dictated by local environmental cues. Here, we report that astrocytes in areas outside of the SGZ and SVZ of adult mice express high levels of ephrin-A2 and -A3, which present an inhibitory niche, negatively regulating neural progenitor cell growth. Adult mice lacking both ephrin-A2 and -A3 display active ongoing neurogenesis throughout the CNS. These findings suggest that neural cell replacement therapies for neurodegeneration or injury in the adult CNS may be achieved by manipulating ephrin signaling pathways.}, Author = {Jiao, Jian-Wei and Feldheim, David A and Chen, Dong Feng}, Date-Added = {2017-11-01 21:08:18 +0000}, Date-Modified = {2017-11-01 21:08:18 +0000}, Doi = {10.1073/pnas.0708861105}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Astrocytes; Cell Differentiation; Central Nervous System; Ephrin-A2; Ephrin-A3; Ephrins; Mice; Mice, Transgenic; Neurons; Receptor, EphA7; Signal Transduction}, Month = {Jun}, Number = {25}, Pages = {8778-83}, Pmc = {PMC2438395}, pmid = {18562299}, Pst = {ppublish}, Title = {Ephrins as negative regulators of adult neurogenesis in diverse regions of the central nervous system}, Volume = {105}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0708861105}} @article{Triplett:2014, Abstract = {BACKGROUND: There are numerous functional types of retinal ganglion cells (RGCs), each participating in circuits that encode a specific aspect of the visual scene. This functional specificity is derived from distinct RGC morphologies and selective synapse formation with other retinal cell types; yet, how these properties are established during development remains unclear. Islet2 (Isl2) is a LIM-homeodomain transcription factor expressed in the developing retina, including approximately 40% of all RGCs, and has previously been implicated in the subtype specification of spinal motor neurons. Based on this, we hypothesized that Isl2+ RGCs represent a related subset that share a common function. RESULTS: We morphologically and molecularly characterized Isl2+ RGCs using a transgenic mouse line that expresses GFP in the cell bodies, dendrites and axons of Isl2+ cells (Isl2-GFP). Isl2-GFP RGCs have distinct morphologies and dendritic stratification patterns within the inner plexiform layer and project to selective visual nuclei. Targeted filling of individual cells reveals that the majority of Isl2-GFP RGCs have dendrites that are monostratified in layer S3 of the IPL, suggesting they are not ON-OFF direction-selective ganglion cells. Molecular analysis shows that most alpha-RGCs, indicated by expression of SMI-32, are also Isl2-GFP RGCs. Isl2-GFP RGCs project to most retino-recipient nuclei during early development, but specifically innervate the dorsal lateral geniculate nucleus and superior colliculus (SC) at eye opening. Finally, we show that the segregation of Isl2+ and Isl2- RGC axons in the SC leads to the segregation of functional RGC types. CONCLUSIONS: Taken together, these data suggest that Isl2+ RGCs comprise a distinct class and support a role for Isl2 as an important component of a transcription factor code specifying functional visual circuits. Furthermore, this study describes a novel genetically-labeled mouse line that will be a valuable resource in future investigations of the molecular mechanisms of visual circuit formation.}, Author = {Triplett, Jason W and Wei, Wei and Gonzalez, Cristina and Sweeney, Neal T and Huberman, Andrew D and Feller, Marla B and Feldheim, David A}, Date-Added = {2017-11-01 21:08:07 +0000}, Date-Modified = {2017-11-01 21:08:07 +0000}, Doi = {10.1186/1749-8104-9-2}, Journal = {Neural Dev}, Journal-Full = {Neural development}, Mesh = {Animals; Axons; Dendrites; Geniculate Bodies; LIM-Homeodomain Proteins; Mice; Mice, Transgenic; Neural Pathways; Retinal Ganglion Cells; Superior Colliculi; Transcription Factors}, Month = {Feb}, Pages = {2}, Pmc = {PMC3937143}, pmid = {24495295}, Pst = {epublish}, Title = {Dendritic and axonal targeting patterns of a genetically-specified class of retinal ganglion cells that participate in image-forming circuits}, Volume = {9}, Year = {2014}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1749-8104-9-2}} @article{Sweeney:2014, Abstract = {There are ∼20 types of retinal ganglion cells (RGCs) in mice, each of which has distinct molecular, morphological, and physiological characteristics. Each RGC type sends axon projections to specific brain areas that execute light-dependent behaviors. Here, we show that the T-box transcription factor Tbr2 is required for the development of several RGC types that participate in non-image-forming circuits. These types are molecularly distinct, project to non-image-forming targets, and include intrinsically photosensitive RGCs. Tbr2 mutant mice have reduced retinal projections to non-image-forming nuclei and an attenuated pupillary light reflex. These data demonstrate that Tbr2 acts to execute RGC type choice and/or survival in a set of RGCs that mediates light-induced subconscious behaviors.}, Author = {Sweeney, Neal T and Tierney, Hannah and Feldheim, David A}, Date-Added = {2017-11-01 21:08:01 +0000}, Date-Modified = {2017-11-01 21:08:01 +0000}, Doi = {10.1523/JNEUROSCI.0035-14.2014}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {TBR2; axon projections; retina; visual circuit}, Mesh = {Age Factors; Animals; Animals, Newborn; Axons; Cadherins; Calbindin 2; Female; Gene Expression Regulation; Green Fluorescent Proteins; Male; Mice; Mice, Transgenic; Mutation; Pupil; Receptors, Dopamine D4; Reflex; Retinal Ganglion Cells; T-Box Domain Proteins; Visual Pathways}, Month = {Apr}, Number = {16}, Pages = {5447-53}, Pmc = {PMC3988404}, pmid = {24741035}, Pst = {ppublish}, Title = {Tbr2 is required to generate a neural circuit mediating the pupillary light reflex}, Volume = {34}, Year = {2014}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0035-14.2014}} @article{Sweeney:2015, Abstract = {In the retinocollicular projection, the axons from functionally distinct retinal ganglion cell (RGC) types form synapses in a stereotypical manner along the superficial to deep axis of the superior colliculus (SC). Each lamina contains an orderly topographic map of the visual scene but different laminae receive inputs from distinct sets of RGCs, and inputs to each lamina are aligned with the others to integrate parallel streams of visual information. To determine the relationship between laminar organization and topography of physiologically defined RGC types, we used genetic and anatomical axon tracing techniques in wild type and ephrin-A mutant mice. We find that adjacent RGCs of the same physiological type can send axons to both ectopic and normal topographic locations, supporting a penetrance model for ephrin-A independent mapping cues. While the overall laminar organization in the SC is unaffected in ephrin-A2/A5 double mutant mice, analysis of the laminar locations of ectopic terminations shows that the topographic maps of different RGC types are misaligned. These data lend support to the hypothesis that the retinocollicular projection is a superimposition of a number of individual two-dimensional topographic maps that originate from specific types of RGCs, require ephrin-A signaling, and form independently of the other maps.}, Author = {Sweeney, Neal T and James, Kiely N and Sales, Emily C and Feldheim, David A}, Date-Added = {2017-11-01 21:07:56 +0000}, Date-Modified = {2017-11-01 21:07:56 +0000}, Doi = {10.1002/dneu.22265}, Journal = {Dev Neurobiol}, Journal-Full = {Developmental neurobiology}, Keywords = {ephrin-A; topographic mapping; visual system development}, Mesh = {Amino Acids; Animals; Brain; Brain Mapping; Ephrins; Mice; Mice, Transgenic; Mutation; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways}, Month = {Jun}, Number = {6}, Pages = {584-93}, Pmc = {PMC4437846}, pmid = {25649160}, Pst = {ppublish}, Title = {Ephrin-As are required for the topographic mapping but not laminar choice of physiologically distinct RGC types}, Volume = {75}, Year = {2015}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dneu.22265}} @article{Owens:2015, Abstract = {Topographic maps in visual processing areas maintain the spatial order of the visual world. Molecular cues and neuronal activity both play critical roles in map formation, but their interaction remains unclear. Here, we demonstrate that when molecular- and activity-dependent cues are rendered nearly equal in force, they drive topographic mapping stochastically. The functional and anatomical representation of azimuth in the superior colliculus of heterozygous Islet2-EphA3 knockin (Isl2(EphA3/+)) mice is variable: maps may be single, duplicated, or a combination of the two. This heterogeneity is not due to genetic differences, since map organizations in individual mutant animals often differ between colliculi. Disruption of spontaneous waves of retinal activity resulted in uniform map organization in Isl2(EphA3/+) mice, demonstrating that correlated spontaneous activity is required for map heterogeneity. Computational modeling replicates this heterogeneity, revealing that molecular- and activity-dependent forces interact simultaneously and stochastically during topographic map formation.}, Author = {Owens, Melinda T and Feldheim, David A and Stryker, Michael P and Triplett, Jason W}, Date-Added = {2017-11-01 21:07:51 +0000}, Date-Modified = {2017-11-01 21:07:51 +0000}, Doi = {10.1016/j.neuron.2015.08.030}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Brain Mapping; Cues; Gene Knock-In Techniques; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Retinal Ganglion Cells; Stochastic Processes; Superior Colliculi; Visual Pathways}, Month = {Sep}, Number = {6}, Pages = {1261-73}, Pmc = {PMC4583656}, pmid = {26402608}, Pst = {ppublish}, Title = {Stochastic Interaction between Neural Activity and Molecular Cues in the Formation of Topographic Maps}, Volume = {87}, Year = {2015}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.08.030}} @article{Shanks:2016, Abstract = {UNLABELLED: Retinal ganglion cells (RGCs) relay information about the outside world to multiple subcortical targets within the brain. This information is either used to dictate reflexive behaviors or relayed to the visual cortex for further processing. Many subcortical visual nuclei also receive descending inputs from projection neurons in the visual cortex. Most areas receive inputs from layer 5 cortical neurons in the visual cortex but one exception is the dorsal lateral geniculate nucleus (dLGN), which receives layer 6 inputs and is also the only RGC target that sends direct projections to the cortex. Here we ask how visual system development and function changes in mice that develop without a cortex. We find that the development of a cortex is essential for RGC axons to terminate in the dLGN, but is not required for targeting RGC axons to other subcortical nuclei. RGC axons also fail to target to the dLGN in mice that specifically lack cortical layer 6 projections to the dLGN. Finally, we show that when mice develop without a cortex they can still perform a number of vision-dependent tasks. SIGNIFICANCE STATEMENT: The dorsal lateral geniculate nucleus (dLGN) is a sensory thalamic relay area that receives feedforward inputs from retinal ganglion cells (RGCs) in the retina, and feed back inputs from layer 6 neurons in the visual cortex. In this study we examined genetically manipulated mice that develop without a cortex or without cortical layer 6 axonal projections, and find that RGC axons fail to project to the dLGN. Other RGC recipient areas, such as the superior colliculus and suprachiasmatic nucleus, are targeted normally. These results provide support for a new mechanism of target selection that may be specific to the thalamus, whereby descending cortical axons provide an activity that promotes feedforward targeting of RGC axons to the dLGN.}, Author = {Shanks, James A and Ito, Shinya and Schaevitz, Laura and Yamada, Jena and Chen, Bin and Litke, Alan and Feldheim, David A}, Date-Added = {2017-11-01 21:07:47 +0000}, Date-Modified = {2017-11-01 21:07:47 +0000}, Doi = {10.1523/JNEUROSCI.4599-15.2016}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {axon-targeting; cortex; dLGN; retina; target selection; visual system}, Mesh = {Animals; Axon Guidance; Female; Geniculate Bodies; Male; Mice; Retinal Ganglion Cells; Visual Cortex}, Month = {May}, Number = {19}, Pages = {5252-63}, Pmc = {PMC4863061}, pmid = {27170123}, Pst = {ppublish}, Title = {Corticothalamic Axons Are Essential for Retinal Ganglion Cell Axon Targeting to the Mouse Dorsal Lateral Geniculate Nucleus}, Volume = {36}, Year = {2016}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4599-15.2016}} @article{Sweeney:2017, Abstract = {Retinal ganglion cells (RGCs) are tasked with transmitting all light information from the eye to the retinal recipient areas of the brain. RGCs can be classified into many different types by morphology, gene expression, axonal projections, and functional responses to different light stimuli. Ultimately, these classification systems should be unified into an all-encompassing taxonomy. Toward that end, we show here that nearly all RGCs express either Islet-2 (Isl2), Tbr2, or a combination of Satb1 and Satb2. We present gene expression data supporting the hypothesis that Satb1 and Satb2 are expressed in ON-OFF direction-selective (DS) RGCs, complementing our previous work demonstrating that RGCs that express Isl2 and Tbr2 are non-DS and non-image-forming, respectively. Expression of these transcription factors emerges at distinct embryonic ages and only in postmitotic cells. Finally, we demonstrate that these transcription factor-defined RGC classes are born throughout RGC genesis.}, Author = {Sweeney, Neal T and James, Kiely N and Nistorica, Andreea and Lorig-Roach, Ryan M and Feldheim, David A}, Date-Added = {2017-11-01 21:07:37 +0000}, Date-Modified = {2017-11-01 21:07:37 +0000}, Doi = {10.1002/cne.24172}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {RRID: AB_10615604; RRID: AB_11143446; RRID: AB_1608077; RRID: AB_2167511; RRID: AB_2301417; RRID: AB_2313614; RRID: AB_231491; RRID: AB_882455; cell fate; retinal ganglion cells; transcription factors}, Month = {Jan}, pmid = {28078709}, Pst = {aheadofprint}, Title = {Expression of transcription factors divides retinal ganglion cells into distinct classes}, Year = {2017}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.24172}} @article{Ito:2017, Abstract = {The superior colliculus (SC) receives direct input from the retina and integrates it with information about sound, touch, and state of the animal that is relayed from other parts of the brain to initiate specific behavioral outcomes. The superficial SC layers (sSC) contain cells that respond to visual stimuli, whereas the deep SC layers (dSC) contain cells that also respond to auditory and somatosensory stimuli. Here, we used a large-scale silicon probe recording system to examine the visual response properties of SC cells of head-fixed and alert male mice. We found cells with diverse response properties including: (1) orientation/direction-selective (OS/DS) cells with a firing rate that is suppressed by drifting sinusoidal gratings (negative OS/DS cells); (2) suppressed-by-contrast cells; (3) cells with complex-like spatial summation nonlinearity; and (4) cells with Y-like spatial summation nonlinearity. We also found specific response properties that are enriched in different depths of the SC. The sSC is enriched with cells with small RFs, high evoked firing rates (FRs), and sustained temporal responses, whereas the dSC is enriched with the negative OS/DS cells and with cells with large RFs, low evoked FRs, and transient temporal responses. Locomotion modulates the activity of the SC cells both additively and multiplicatively and changes the preferred spatial frequency of some SC cells. These results provide the first description of the negative OS/DS cells and demonstrate that the SC segregates cells with different response properties and that the behavioral state of a mouse affects SC activity.SIGNIFICANCE STATEMENT The superior colliculus (SC) receives visual input from the retina in its superficial layers (sSC) and induces eye/head-orientating movements and innate defensive responses in its deeper layers (dSC). Despite their importance, very little is known about the visual response properties of dSC neurons. Using high-density electrode recordings and novel model-based analysis, we found several novel visual response properties of the SC cells, including encoding of a cell's preferred orientation or direction by suppression of the firing rate. The sSC and the dSC are enriched with cells with different visual response properties. Locomotion modulates the cells in the SC. These findings contribute to our understanding of how the SC processes visual inputs, a critical step in comprehending visually guided behaviors.}, Author = {Ito, Shinya and Feldheim, David A and Litke, Alan M}, Date-Added = {2017-11-01 21:07:32 +0000}, Date-Modified = {2017-11-01 21:07:32 +0000}, Doi = {10.1523/JNEUROSCI.3689-16.2017}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {mouse; silicon probe; superior colliculus; vision}, Mesh = {Adaptation, Physiological; Animals; Gait; Locomotion; Male; Mice; Mice, Inbred C57BL; Nerve Net; Neuronal Plasticity; Spatial Navigation; Superior Colliculi; Visual Perception}, Month = {Aug}, Number = {35}, Pages = {8428-8443}, Pmc = {PMC5577856}, pmid = {28760858}, Pst = {ppublish}, Title = {Segregation of Visual Response Properties in the Mouse Superior Colliculus and Their Modulation during Locomotion}, Volume = {37}, Year = {2017}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3689-16.2017}} @article{Scalia:2009, Abstract = {Eph/ephrin-receptor/ligand A and B families play a variety of roles during CNS development, including patterning the retinotectal projection. However, the alignment of their expression gradients with developing retinotectal maps and gradients of cellular development is not well understood in species whose midbrain tecta undergo a protracted anterior to posterior development. By using anatomical tracing methods and (3)H-thymidine neuronography, we have mapped the retinotectal projection and the spatiotemporal progression of tectal cellular development onto Eph/ephrin expression patterns in the tectum of larval Rana pipiens, as studied by means of in situ affinity analysis with fusion proteins. EphA expression is maximal in anterior tectum (and temporal retina); ephrin-A expression is maximal at the posterior pole (and nasal retina). EphB expression is graded in the early larva, where it is maximal in the posterior tectum just anterior to the posterior pole (and in the ventral retina). Tectal EphB expression becomes uniform at later stages and remains so in the adult, although its retinal expression remains maximal ventrally. In the early larva, EphA, EphB, and ephrin-A protein gradients are parallel to each other and align with the temporonasal axis of the retinal projection. The early EphB expression maximum overlaps the boundary between the mantle layer of newly postmitotic cells and the posterior, epithelial region of cell proliferation, suggesting that the expression maximum is associated with the initial migrations of the postmitotic cells. Ephrin-B expression was detected in the olfactory bulb and dorsal retina at all ages, but not in the tectum.}, Author = {Scalia, Frank and Currie, Julia R and Feldheim, David A}, Date-Added = {2017-11-01 21:07:01 +0000}, Date-Modified = {2017-11-01 21:07:01 +0000}, Doi = {10.1002/cne.21968}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Ephrins; Larva; Prosencephalon; Rana pipiens; Receptors, Eph Family; Retina; Tectum Mesencephali; Visual Pathways}, Month = {May}, Number = {1}, Pages = {30-48}, pmid = {19260054}, Pst = {ppublish}, Title = {Eph/ephrin gradients in the retinotectal system of Rana pipiens: developmental and adult expression patterns}, Volume = {514}, Year = {2009}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21968}} @article{Feldheim:2010, Abstract = {Topographic maps are a two-dimensional representation of one neural structure within another and serve as the main strategy to organize sensory information. The retina's projection via axons of retinal ganglion cells to midbrain visual centers, the optic tectum/superior colliculus, is the leading model to elucidate mechanisms of topographic map formation. Each axis of the retina is mapped independently using different mechanisms and sets of axon guidance molecules expressed in gradients to achieve the goal of representing a point in the retina onto a point within the target. An axon's termination along the temporal-nasal mapping axis is determined by opposing gradients of EphAs and ephrin-As that act through their forward and reverse signaling, respectively, within the projecting axons, each of which inhibits interstitial branching, cooperating with a branch-promoting activity, to generate topographic specific branching along the shaft of the parent axons that overshoot their correct termination zone along the anterior-posterior axis of the target. The dorsal-ventral termination position is then determined using a gradient of ephrin-B that can act as a repellent or attractant depending on the ephrin-B concentration relative to EphB levels on the interstitial branches to guide them along the medial-lateral axis of the target to their correct termination zone, where they arborize. In both cases, axon-axon competition results in axon mapping based on relative rather than absolute levels of repellent or attractant activity. The map is subsequently refined through large-scale pruning driven in large part by patterned retinal activity.}, Author = {Feldheim, David A and O'Leary, Dennis D M}, Date-Added = {2017-11-01 21:06:54 +0000}, Date-Modified = {2017-11-01 21:06:54 +0000}, Doi = {10.1101/cshperspect.a001768}, Journal = {Cold Spring Harb Perspect Biol}, Journal-Full = {Cold Spring Harbor perspectives in biology}, Mesh = {Animals; Brain; Brain Mapping; Ephrins; Humans; Receptors, Eph Family; Retina; Retinal Ganglion Cells; Signal Transduction; Visual Pathways}, Month = {Nov}, Number = {11}, Pages = {a001768}, Pmc = {PMC2964178}, pmid = {20880989}, Pst = {ppublish}, Title = {Visual map development: bidirectional signaling, bifunctional guidance molecules, and competition}, Volume = {2}, Year = {2010}, Bdsk-Url-1 = {http://dx.doi.org/10.1101/cshperspect.a001768}} @article{Higenell:2012, Abstract = {The Eph family of receptor tyrosine kinases and their ligands the ephrins play an essential role in the targeting of retinal ganglion cell axons to topographically correct locations in the optic tectum during visual system development. The African claw-toed frog Xenopus laevis is a popular animal model for the study of retinotectal development because of its amenability to live imaging and electrophysiology. Its visual system undergoes protracted growth continuing beyond metamorphosis, yet little is known about ephrin and Eph expression patterns beyond stage 39 when retinal axons first arrive in the tectum. We used alkaline phosphatase fusion proteins of EphA3, ephrin-A5, EphB2, and ephrin-B1 as affinity probes to reveal the expression patterns of ephrin-As, EphAs, ephrin-Bs, and EphBs, respectively. Analysis of brains from stage 40 to adult frog revealed that ephrins and Eph receptors are expressed throughout development. As observed in other species, staining for ephrin-As displayed a high caudal to low rostral expression pattern across the tectum, roughly complementary to the expression of EphAs. In contrast with the prevailing model, EphBs were found to be expressed in the tectum in a high dorsal to low ventral gradient in young animals. In animals with induced binocular tectal innervation, ocular dominance bands of alternating input from the two eyes formed in the tectum; however, ephrin-A and EphA expression patterns were unmodulated and similar to those in normal frogs, confirming that the segregation of axons into eye-specific stripes is not the consequence of a respecification of molecular guidance cues in the tectum.}, Author = {Higenell, Valerie and Han, Sang Myung and Feldheim, David A and Scalia, Frank and Ruthazer, Edward S}, Date-Added = {2017-11-01 21:06:46 +0000}, Date-Modified = {2017-11-01 21:06:46 +0000}, Doi = {10.1002/dneu.20930}, Journal = {Dev Neurobiol}, Journal-Full = {Developmental neurobiology}, Mesh = {Animals; Ephrins; Gene Expression Profiling; Neurogenesis; Receptor, EphA1; Retina; Superior Colliculi; Xenopus laevis}, Month = {Apr}, Number = {4}, Pages = {547-63}, Pmc = {PMC3395774}, pmid = {21656698}, Pst = {ppublish}, Title = {Expression patterns of Ephs and ephrins throughout retinotectal development in Xenopus laevis}, Volume = {72}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dneu.20930}} @article{Osterhout:2011, Abstract = {Neural circuits consist of highly precise connections among specific types of neurons that serve a common functional goal. How neurons distinguish among different synaptic targets to form functionally precise circuits remains largely unknown. Here, we show that during development, the adhesion molecule cadherin-6 (Cdh6) is expressed by a subset of retinal ganglion cells (RGCs) and also by their targets in the brain. All of the Cdh6-expressing retinorecipient nuclei mediate non-image-forming visual functions. A screen of mice expressing GFP in specific subsets of RGCs revealed that Cdh3-RGCs which also express Cdh6 selectively innervate Cdh6-expressing retinorecipient targets. Moreover, in Cdh6-deficient mice, the axons of Cdh3-RGCs fail to properly innervate their targets and instead project to other visual nuclei. These findings provide functional evidence that classical cadherins promote mammalian CNS circuit development by ensuring that axons of specific cell types connect to their appropriate synaptic targets.}, Author = {Osterhout, Jessica A and Josten, Nicko and Yamada, Jena and Pan, Feng and Wu, Shaw-wen and Nguyen, Phong L and Panagiotakos, Georgia and Inoue, Yukiko U and Egusa, Saki F and Volgyi, Bela and Inoue, Takayoshi and Bloomfield, Stewart A and Barres, Ben A and Berson, David M and Feldheim, David A and Huberman, Andrew D}, Date-Added = {2017-11-01 21:06:29 +0000}, Date-Modified = {2017-11-01 21:06:29 +0000}, Doi = {10.1016/j.neuron.2011.07.006}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Axons; Cadherins; Green Fluorescent Proteins; Mice; Mice, Knockout; Nerve Net; Retinal Ganglion Cells; Visual Cortex; Visual Pathways}, Month = {Aug}, Number = {4}, Pages = {632-9}, Pmc = {PMC3513360}, pmid = {21867880}, Pst = {ppublish}, Title = {Cadherin-6 mediates axon-target matching in a non-image-forming visual circuit}, Volume = {71}, Year = {2011}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.07.006}} @article{Triplett:2012a, Abstract = {The axonal connections between the retina and its midbrain target, the superior colliculus (SC), is mapped topographically, such that the spatial relationships of cell bodies in the retina are maintained when terminating in the SC. Topographic map development uses a Cartesian mapping system such that each axis of the retina is mapped independently. Along the nasal-temporal mapping axis, EphAs and ephrin-As, are graded molecular cues required for topographic mapping while the dorsal-ventral axis is mapped in part via EphB and ephrin-Bs. Because both Ephs and ephrins are cell surface molecules they can signal in the forward and reverse directions. Eph/ephrin signaling leads to changes in cytoskeletal dynamics that lead to actin depolymerization and endocytosis guiding axons via attraction and repulsion.}, Author = {Triplett, Jason W and Feldheim, David A}, Date-Added = {2017-11-01 21:06:20 +0000}, Date-Modified = {2017-11-01 21:06:20 +0000}, Doi = {10.1016/j.semcdb.2011.10.026}, Journal = {Semin Cell Dev Biol}, Journal-Full = {Seminars in cell \& developmental biology}, Mesh = {Animals; Brain Mapping; Ephrins; Gene Expression; Humans; Receptors, Eph Family; Retinal Ganglion Cells; Signal Transduction; Superior Colliculi; Synapses; Visual Perception}, Month = {Feb}, Number = {1}, Pages = {7-15}, Pmc = {PMC3288406}, pmid = {22044886}, Pst = {ppublish}, Title = {Eph and ephrin signaling in the formation of topographic maps}, Volume = {23}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.semcdb.2011.10.026}} @article{Triplett:2011, Abstract = {Topographic maps are the primary means of relaying spatial information in the brain. Understanding the mechanisms by which they form has been a goal of experimental and theoretical neuroscientists for decades. The projection of the retina to the superior colliculus (SC)/tectum has been an important model used to show that graded molecular cues and patterned retinal activity are required for topographic map formation. Additionally, interaxon competition has been suggested to play a role in topographic map formation; however, this view has been recently challenged. Here we present experimental and computational evidence demonstrating that interaxon competition for target space is necessary to establish topography. To test this hypothesis experimentally, we determined the nature of the retinocollicular projection in Math5 (Atoh7) mutant mice, which have severely reduced numbers of retinal ganglion cell inputs into the SC. We find that in these mice, retinal axons project to the anteromedialj portion of the SC where repulsion from ephrin-A ligands is minimized and where their attraction to the midline is maximized. This observation is consistent with the chemoaffinity model that relies on axon-axon competition as a mapping mechanism. We conclude that chemical labels plus neural activity cannot alone specify the retinocollicular projection; instead axon-axon competition is necessary to create a map. Finally, we present a mathematical model for topographic mapping that incorporates molecular labels, neural activity, and axon competition.}, Author = {Triplett, Jason W and Pfeiffenberger, Cory and Yamada, Jena and Stafford, Ben K and Sweeney, Neal T and Litke, Alan M and Sher, Alexander and Koulakov, Alexei A and Feldheim, David A}, Date-Added = {2017-11-01 21:06:11 +0000}, Date-Modified = {2017-11-01 21:06:11 +0000}, Doi = {10.1073/pnas.1102834108}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Axons; Basic Helix-Loop-Helix Transcription Factors; Fluorescence; Humans; Mice; Mice, Mutant Strains; Models, Biological; Nerve Tissue Proteins; Retina; Space Perception; Statistics, Nonparametric; Superior Colliculi; Visual Pathways; Visual Perception}, Month = {Nov}, Number = {47}, Pages = {19060-5}, Pmc = {PMC3223436}, pmid = {22065784}, Pst = {ppublish}, Title = {Competition is a driving force in topographic mapping}, Volume = {108}, Year = {2011}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1102834108}} @article{Clandinin:2009, Abstract = {Visual system development utilizes global and local cues to assemble a topographic map of the visual world, arranging synaptic connections into columns and layers. Recent genetic studies have provided new insights into the mechanisms that underlie these processes. In flies, a precise temporal sequence of neural differentiation provides a global organizing cue; in vertebrates, gradients of ephrin-mediated signals, acting with neurotrophin co-receptors and neural activity, play crucial roles. In flies and mice, neural processes tile into precise arrays through homotypic, repulsive interactions, autocrine signals, and cell-intrinsic mechanisms. Laminar targeting specificity is achieved through temporally regulated cell-cell adhesion, as well as combinatorial expression of specific adhesion molecules. Future studies will define the interactions between these global and local cues.}, Author = {Clandinin, Thomas R and Feldheim, David A}, Date-Added = {2017-11-01 21:05:54 +0000}, Date-Modified = {2017-11-01 21:05:54 +0000}, Doi = {10.1016/j.conb.2009.04.011}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Mesh = {Animals; Brain; Neurons; Retina; Time Factors; Visual Pathways; Visual Perception}, Month = {Apr}, Number = {2}, Pages = {174-80}, Pmc = {PMC2726114}, pmid = {19481440}, Pst = {ppublish}, Title = {Making a visual map: mechanisms and molecules}, Volume = {19}, Year = {2009}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2009.04.011}} @article{Pfeiffenberger:2006, Abstract = {The development of topographic maps in the primary visual system is thought to rely on a combination of EphA/ephrin-A interactions and patterned neural activity. Here, we characterize the retinogeniculate and retinocollicular maps of mice mutant for ephrins-A2, -A3, and -A5 (the three ephrin-As expressed in the mouse visual system), mice mutant for the beta2 subunit of the nicotinic acetylcholine receptor (that lack early patterned retinal activity), and mice mutant for both ephrin-As and beta2. We also provide the first comprehensive anatomical description of the topographic connections between the retina and the dorsal lateral geniculate nucleus. We find that, although ephrin-A2/A3/A5 triple knock-out mice have severe mapping defects in both projections, they do not completely lack topography. Mice lacking beta2-dependent retinal activity have nearly normal topography but fail to refine axonal arbors. Mice mutant for both ephrin-As and beta2 have synergistic mapping defects that result in a near absence of map in the retinocollicular projection; however, the retinogeniculate projection is not as severely disrupted as the retinocollicular projection is in these mutants. These results show that ephrin-As and patterned retinal activity act together to establish topographic maps, and demonstrate that midbrain and forebrain connections have a differential requirement for ephrin-As and patterned retinal activity in topographic map development.}, Author = {Pfeiffenberger, Cory and Yamada, Jena and Feldheim, David A}, Date-Added = {2017-11-01 21:05:26 +0000}, Date-Modified = {2017-11-01 21:05:26 +0000}, Doi = {10.1523/JNEUROSCI.3595-06.2006}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Brain Mapping; Ephrin-A2; Ephrin-A5; Ephrins; Geniculate Bodies; Mice; Mice, Inbred C57BL; Mice, Knockout; Retina; Visual Pathways}, Month = {Dec}, Number = {50}, Pages = {12873-84}, Pmc = {PMC3664553}, pmid = {17167078}, Pst = {ppublish}, Title = {Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3595-06.2006}} @article{Scalia:2005, Abstract = {Eph/ephrin expression was studied in Rana utricularia larvae and adults with in situ receptor and ligand affinity probes. From stages TK-II (early limb bud) to VI (early foot paddle larva), tectal EphB expression is highest in a band extending transversely across the posterior optic tectum and grades off anteriorly and posteriorly. The ephrin-A expression gradient is parallel to the EphB gradient rather than being orthogonal to it. However, its high point occupies the posterior pole, and it runs from high-posteriorly to low-anteriorly. Tectal EphA expression is high anteriorly and low posteriorly, while ephrin-Bs are expressed only in a thin line at the dorsal midline. At later stages and in adults, tectal EphB expression becomes uniform.}, Author = {Scalia, Frank and Feldheim, David A}, Date-Added = {2017-11-01 21:04:37 +0000}, Date-Modified = {2017-11-01 21:04:37 +0000}, Doi = {10.1016/j.devbrainres.2005.05.002}, Journal = {Brain Res Dev Brain Res}, Journal-Full = {Brain research. Developmental brain research}, Mesh = {Animals; Body Patterning; Cell Line; Ephrins; Gene Expression Regulation, Developmental; Immunoprecipitation; Larva; Ligands; Mice; Protein Binding; Rana pipiens; Receptors, Eph Family; Superior Colliculi; Transfection; Visual Pathways}, Month = {Aug}, Number = {1-2}, Pages = {102-6}, pmid = {16002151}, Pst = {ppublish}, Title = {Eph/ephrin A- and B-family expression patterns in the leopard frog (Rana utricularia)}, Volume = {158}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devbrainres.2005.05.002}} @article{Ellsworth:2005, Abstract = {Sensory axons are targeted to modality-specific nuclei in the thalamus. Retinal ganglion cell axons project retinotopically to their principal thalamic target, the dorsal lateral geniculate nucleus (LGd), in a pattern likely dictated by the expression of molecular gradients in the LGd. Deafferenting the auditory thalamus induces retinal axons to innervate the medial geniculate nucleus (MGN). These retino-MGN projections also show retinotopic organization. Here we show that ephrin-A2 and -A5, which are expressed in similar gradients in the MGN and LGd, can be used to pattern novel retinal projections in the MGN. As in the LGd, retinal axons from each eye terminate in discrete eye-specific zones in the MGN of rewired wild-type and ephrin-A2/A5 knockout mice. However, ipsilateral eye axons, which arise from retinal regions of high EphA5 receptor expression and represent central visual field, terminate in markedly different ways in the two mice. In rewired wild-type mice, ipsilateral axons specifically avoid areas of high ephrin expression in the MGN. In rewired ephrin knockout mice, ipsilateral projections shift in location and spread more broadly, leading to an expanded representation of the ipsilateral eye in the MGN. Similarly, ipsilateral projections to the LGd in ephrin knockout mice are shifted and are more widespread than in the LGd of wild-type mice. In the MGN, as in the LGd, terminations from the two eyes show little overlap even in the knockout mice, suggesting that local interocular segregation occurs regardless of other patterning determinants. Our data demonstrate that graded topographic labels, such as the ephrins, can serve to shape multiple related aspects of afferent patterning, including topographic mapping and the extent and spread of eye-specific projections. Furthermore, when mapping labels and other cues are expressed in multiple target zones, novel projections are patterned according to rules that operate in their canonical targets.}, Author = {Ellsworth, Charlene A and Lyckman, Alvin W and Feldheim, David A and Flanagan, John G and Sur, Mriganka}, Date-Added = {2017-11-01 21:04:31 +0000}, Date-Modified = {2017-11-01 21:04:31 +0000}, Doi = {10.1002/cne.20602}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Animals, Newborn; Axons; Brain Mapping; Cholera Toxin; Ephrin-A2; Ephrin-A5; Eye; Functional Laterality; Gene Expression Regulation; Geniculate Bodies; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Neurological; Retina; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways}, Month = {Jul}, Number = {2}, Pages = {140-51}, pmid = {15924339}, Pst = {ppublish}, Title = {Ephrin-A2 and -A5 influence patterning of normal and novel retinal projections to the thalamus: conserved mapping mechanisms in visual and auditory thalamic targets}, Volume = {488}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20602}} @article{Himanen:2004, Abstract = {The interactions between Eph receptor tyrosine kinases and their ephrin ligands regulate cell migration and axon pathfinding. The EphA receptors are generally thought to become activated by ephrin-A ligands, whereas the EphB receptors interact with ephrin-B ligands. Here we show that two of the most widely studied of these molecules, EphB2 and ephrin-A5, which have never been described to interact with each other, do in fact bind one another with high affinity. Exposure of EphB2-expressing cells to ephrin-A5 leads to receptor clustering, autophosphorylation and initiation of downstream signaling. Ephrin-A5 induces EphB2-mediated growth cone collapse and neurite retraction in a model system. We further show, using X-ray crystallography, that the ephrin-A5-EphB2 complex is a heterodimer and is architecturally distinct from the tetrameric EphB2-ephrin-B2 structure. The structural data reveal the molecular basis for EphB2-ephrin-A5 signaling and provide a framework for understanding the complexities of functional interactions and crosstalk between A- and B-subclass Eph receptors and ephrins.}, Author = {Himanen, Juha-Pekka and Chumley, Michael J and Lackmann, Martin and Li, Chen and Barton, William A and Jeffrey, Phillip D and Vearing, Christopher and Geleick, Detlef and Feldheim, David A and Boyd, Andrew W and Henkemeyer, Mark and Nikolov, Dimitar B}, Date-Added = {2017-11-01 21:04:20 +0000}, Date-Modified = {2017-11-01 21:04:20 +0000}, Doi = {10.1038/nn1237}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Alkaline Phosphatase; Animals; Animals, Newborn; Cell Line; Chromatography, Gel; Chromatography, Ion Exchange; Cricetinae; Cricetulus; Crystallography; Electrophoresis; Ephrin-A5; Ephrin-B2; Fluorescent Antibody Technique; Green Fluorescent Proteins; Humans; Infection; Luminescent Proteins; Mice; Neurites; Neuroblastoma; Phosphorylation; Protein Binding; Receptor, EphA3; Receptor, EphB2; Signal Transduction; Sindbis Virus; Spectrometry, Fluorescence; Surface Plasmon Resonance; Time Factors; Transfection; Video Recording}, Month = {May}, Number = {5}, Pages = {501-9}, pmid = {15107857}, Pst = {ppublish}, Title = {Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling}, Volume = {7}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1237}} @article{Feng:2000a, Abstract = {Motor axons form topographic maps on muscles: rostral motor pools innervate rostral muscles, and rostral portions of motor pools innervate rostral fibers within their targets. Here, we implicate A subfamily ephrins in this topographic mapping. First, developing muscles express all five of the ephrin-A genes. Second, rostrally and caudally derived motor axons differ in sensitivity to outgrowth inhibition by ephrin-A5. Third, the topographic map of motor axons on the gluteus muscle is degraded in transgenic mice that overexpress ephrin-A5 in muscles. Fourth, topographic mapping is impaired in muscles of mutant mice lacking ephrin-A2 plus ephrin-A5. Thus, ephrins mediate or modulate positionally selective synapse formation. In addition, the rostrocaudal position of at least one motor pool is altered in ephrin-A5 mutant mice, indicating that ephrins affect nerve-muscle matching by intraspinal as well as intramuscular mechanisms.}, Author = {Feng, G and Laskowski, M B and Feldheim, D A and Wang, H and Lewis, R and Frisen, J and Flanagan, J G and Sanes, J R}, Date-Added = {2017-11-01 21:03:24 +0000}, Date-Modified = {2017-11-01 21:03:24 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Axons; Cell Communication; Cells, Cultured; Ephrin-A2; Ephrin-A5; Fibroblasts; Gene Expression; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Knockout; Motor Neurons; Muscle Fibers, Skeletal; Muscle, Skeletal; Neuromuscular Junction; Spinal Cord; Synapses; Transcription Factors}, Month = {Feb}, Number = {2}, Pages = {295-306}, pmid = {10719886}, Pst = {ppublish}, Title = {Roles for ephrins in positionally selective synaptogenesis between motor neurons and muscle fibers}, Volume = {25}, Year = {2000}} @article{Feldheim:2000, Abstract = {Ephrin-A2 and -A5 are thought to be anteroposterior mapping labels for the retinotectal/retinocollicular projection. Here, gene disruptions of both these ephrins are characterized. Focal retinal labeling reveals moderate map abnormalities when either gene is disrupted. Double heterozygotes also have a phenotype, showing an influence of absolute levels. In vitro assays indicate these ephrins are required for repellent activity in the target and also normal responsiveness in the retina. In double homozygotes, anteroposterior order is almost though not completely lost. Temporal or nasal retinal labelings reveal quantitatively similar but opposite shifts, with multiple terminations scattered widely over the target. These results indicate an axon competition mechanism for mapping, with a critical role for ephrins as anteroposterior topographic labels. Dorsoventral topography is also impaired, showing these ephrins are required in mapping both axes.}, Author = {Feldheim, D A and Kim, Y I and Bergemann, A D and Fris{\'e}n, J and Barbacid, M and Flanagan, J G}, Date-Added = {2017-11-01 21:03:20 +0000}, Date-Modified = {2017-11-01 21:03:20 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Axons; Biomarkers; Brain Mapping; Ephrin-A2; Ephrin-A3; Ephrin-A5; Gene Expression Regulation, Developmental; Membrane Proteins; Mice; Mice, Knockout; Phenotype; RNA, Messenger; Retina; Superior Colliculi; Transcription Factors; Visual Pathways}, Month = {Mar}, Number = {3}, Pages = {563-74}, pmid = {10774725}, Pst = {ppublish}, Title = {Genetic analysis of ephrin-A2 and ephrin-A5 shows their requirement in multiple aspects of retinocollicular mapping}, Volume = {25}, Year = {2000}} @article{Bach:2003, Abstract = {Many studies have demonstrated the involvement of the EphA family of receptor tyrosine kinases and their ligands, ephrin-A2 and -A5, in the development of the temporonasal axis of the retinotectal/collicular map, but the role of these molecules in optic nerve regeneration has not been well studied. Noting that the characteristic gradients of the EphA/ephrin-A family that are expressed topographically in the retina and tectum of embryonic chicks and mice tend to disappear after birth, we took as our starting point an analysis of EphA and ephrin-A expression in leopard frogs (Rana pipiens and utricularia), species capable of regenerating the retinotectal map as adults. For the EphA family to be involved in the regeneration, one would expect these topographic gradients to persist in the adult or, if downregulated after metamorphosis, to be reexpressed after optic nerve injury. Using EphA3 receptor and ephrin-A5 ligand alkaline phosphatase in situ affinity probes (RAP and LAP, respectively) in whole-mount applications, we report that reciprocally complementary gradients of RAP and LAP binding persist in the optic tract and optic tectum of postmetamorphic frogs, including mature adults. EphA expression in temporal retinal axons in the optic tract was significantly reduced after nerve section but returned during regeneration. However, ephrin-A expression in the tectal parenchyma was not significantly elevated by either eye removal, with degeneration of optic axons, or during regeneration of the retinotectal projection. Thus, the present study has demonstrated a persisting expression of EphA/ephrin-A family members in the retinal axons and tectal parenchyma that may help guide regenerating fibers, but we can offer no evidence for an upregulation of ephrin-A expression in conjunction with optic nerve injury.}, Author = {Bach, Helene and Feldheim, David A and Flanagan, John G and Scalia, Frank}, Date-Added = {2017-11-01 21:03:01 +0000}, Date-Modified = {2017-11-01 21:03:01 +0000}, Doi = {10.1002/cne.10941}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Affinity Labels; Alkaline Phosphatase; Animals; Ephrin-A5; Eye Enucleation; Geniculate Bodies; Nerve Regeneration; Optic Nerve; Rana pipiens; Receptors, Eph Family; Superior Colliculi; Visual Pathways}, Month = {Dec}, Number = {4}, Pages = {549-65}, pmid = {14624488}, Pst = {ppublish}, Title = {Persistence of graded EphA/Ephrin-A expression in the adult frog visual system}, Volume = {467}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10941}} @article{Feldheim:2004, Abstract = {EphA tyrosine kinases are thought to act as topographically specific receptors in the well-characterized projection map from the retina to the tectum. Here, we describe a loss-of-function analysis of EphA receptors in retinotectal mapping. Expressing patches of a cytoplasmically truncated EphA3 receptor in chick retina caused temporal axons to have reduced responsiveness to posterior tectal repellent activity in vitro and to shift more posteriorly within the map in vivo. A gene disruption of mouse EphA5, replacing the intracellular domain with beta-galactosidase, reduced in vitro responsiveness of temporal axons to posterior target membranes. It also caused map abnormalities in vivo, with temporal axons shifted posteriorly and nasal axons anteriorly, but with the entire target still filled by retinal axons. The anterior shift of nasal axons was not accompanied by increased responsiveness to tectal repellent activity, in contrast to the comparable anterior shift in ephrin-A knock-outs, helping to resolve a previous ambiguity in interpreting the ephrin gene knock-outs. The results show the functional requirement for endogenous EphA receptors in retinotectal mapping, show that the receptor intracellular domain is required for a forward signaling response to topographic cues, and provide new evidence for a role of axon competition in topographic mapping.}, Author = {Feldheim, David A and Nakamoto, Masaru and Osterfield, Miriam and Gale, Nicholas W and DeChiara, Thomas M and Rohatgi, Rajat and Yancopoulos, George D and Flanagan, John G}, Date-Added = {2017-11-01 21:02:59 +0000}, Date-Modified = {2017-11-01 21:02:59 +0000}, Doi = {10.1523/JNEUROSCI.0239-03.2004}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Axons; Chick Embryo; Gene Targeting; Genes, Reporter; Genetic Vectors; Mice; Mice, Mutant Strains; Receptor, EphA3; Receptor, EphA5; Receptors, Eph Family; Retinal Ganglion Cells; Sequence Deletion; Superior Colliculi; Visual Pathways}, Month = {Mar}, Number = {10}, Pages = {2542-50}, pmid = {15014130}, Pst = {ppublish}, Title = {Loss-of-function analysis of EphA receptors in retinotectal mapping}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0239-03.2004}} @article{Stuart:1904, Author = {Stuart, T P}, Date-Added = {2017-10-27 21:15:19 +0000}, Date-Modified = {2017-10-27 21:15:19 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Month = {Mar}, Number = {1}, Pages = {38-48}, Pmc = {PMC1465472}, pmid = {16992721}, Pst = {ppublish}, Title = {The function of the hyaloid canal and some other new points in the mechanism of the accommodation of the eye for distance}, Volume = {31}, Year = {1904}, url = {papers/Stuart_JPhysiol1904.pdf}} @article{Simpson:1988, Abstract = {1. To compare the spatial organization of the direction selectivity of neurons in the medial terminal nucleus (MTN) of the accessory optic system with that of neurons in the adjacent ventral tegmentum, extracellular single-unit recordings were made in the anesthetized rabbit. The ventral tegmental neurons were located in a region called the visual tegmental relay zone (VTRZ), which is defined by the ventral tegmental terminal field of contralaterally projecting MTN neurons. 2. Some of the present sample of MTN neurons (5 of 34) had monocular receptive fields composed of two parts distinguished by a marked difference in the orientation of their respective direction-selective tuning curves. For one part of the receptive field the preferred excitatory direction was "up," while for the other part it was "down." Such receptive fields for one eye were called bipartite, whereas the more usually encountered MTN receptive fields, which could be characterized by a single direction-selective tuning curve, were called uniform. 3. Of the 16 neurons recorded from the VTRZ, all but one were binocular. For these neurons, both uniform and bipartite receptive fields were found for each eye alone. The only monocular neuron encountered in the VTRZ had a contralateral, bipartite receptive field. 4. The spatial organization of the direction selectivity of bipartite receptive fields strongly suggests that they are suited to represent rotation of the visual field about a horizontal axis located in the vertical plane that divides the receptive field into two parts. 5. The boundary between the two parts of the bipartite receptive fields was found using handheld visual stimuli at one of two azimuthal locations, either close to 45 degrees or between 95 and 125 degrees (the 0 degree reference was rostral in the midsagittal plane). This particular structure of the bipartite receptive fields suggests that their preferred rotation axes have a close spatial relation to the best-response axes of the semicircular canals. 6. Seven VTRZ neurons were antidromically activated by electrical stimulation of the ipsilateral dorsal cap of the inferior olive. Since the receptive fields of VTRZ neurons have many of the structural features characteristic of the receptive fields of rostral dorsal cap neurons we conclude that the spatial organization of the receptive fields of dorsal cap neurons is, for the most part, synthesized prior to the inferior olive.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Simpson, J I and Leonard, C S and Soodak, R E}, Date-Added = {2017-10-27 18:52:35 +0000}, Date-Modified = {2017-10-27 18:52:35 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Mesh = {Animals; Electric Stimulation; Neurons; Optic Chiasm; Photic Stimulation; Rabbits; Rotation; Vision, Ocular; Visual Perception}, Month = {Dec}, Number = {6}, Pages = {2055-72}, pmid = {3236061}, Pst = {ppublish}, Title = {The accessory optic system of rabbit. II. Spatial organization of direction selectivity}, Volume = {60}, Year = {1988}} @article{Collewijn:2000, Abstract = {To characterize vestibulo-ocular reflex (VOR) properties in the time window in which contributions by other systems are minimal, eye movements during the first 50-100 ms after the start of transient angular head accelerations ( approximately 1000 degrees /s(2)) imposed by a torque helmet were analyzed in normal human subjects. Orientations of the head and both eyes were recorded with magnetic search coils (resolution, approximately 1 min arc; 1000 samples/s). Typically, the first response to a head perturbation was an anti-compensatory eye movement with zero latency, peak-velocity of several degrees per second, and peak excursion of several tenths of a degree. This was interpreted as a passive mechanical response to linear acceleration of the orbital tissues caused by eccentric rotation of the eye. The response was modeled as a damped oscillation (approximately 13 Hz) of the orbital contents, approaching a constant eye deviation for a sustained linear acceleration. The subsequent compensatory eye movements showed (like the head movements) a linear increase in velocity, which allowed estimates of latency and gain with linear regressions. After appropriate accounting for the preceding passive eye movements, average VOR latency (for pooled eyes, directions, and subjects) was calculated as 8.6 ms. Paired comparisons between the two eyes revealed that the latency for the eye contralateral to the direction of head rotation was, on average, 1.3 ms shorter than for the ipsilateral eye. This highly significant average inter-ocular difference was attributed to the additional internuclear abducens neuron in the pathway to the ipsilateral eye. Average acceleration gain (ratio between slopes of eye and head velocities) over the first 40-50 ms was approximately 1.1. Instantaneous velocity gain, calculated as Veye(t)/Vhead(t-latency), showed a gradual build-up converging toward unity (often after a slight overshoot). Instantaneous acceleration gain also converged toward unity but showed a much steeper build-up and larger oscillations. This behavior of acceleration and velocity gain could be accounted for by modeling the eye movements as the sum of the passive response to the linear acceleration and the active rotational VOR. Due to the latency and the anticompensatory component, gaze stabilization was never complete. The influence of visual targets was limited. The initial VOR was identical with a distant target (continuously visible or interrupted) and in complete darkness. A near visual target caused VOR gain to rise to a higher level, but the time after which the difference between far and near targets emerged varied between individuals.}, Author = {Collewijn, H and Smeets, J B}, Date-Added = {2017-10-27 18:41:34 +0000}, Date-Modified = {2017-10-27 18:41:34 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Mesh = {Abducens Nerve; Acceleration; Eye Movements; Head Movements; Head Protective Devices; Humans; Magnetics; Models, Neurological; Motion Perception; Photic Stimulation; Reaction Time; Reflex, Vestibulo-Ocular; Rotation; Torque}, Month = {Jul}, Number = {1}, Pages = {376-89}, pmid = {10899212}, Pst = {ppublish}, Title = {Early components of the human vestibulo-ocular response to head rotation: latency and gain}, Volume = {84}, Year = {2000}} @article{Szentagothai:1950, Author = {Szentagothai, J}, Date-Added = {2017-10-27 18:27:53 +0000}, Date-Modified = {2017-10-27 18:28:59 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {reflex, eye, vision, Vestibular Nuclei, Ocular}, Mesh = {Humans; Nervous System Physiological Phenomena; Reflex; Reflex, Vestibulo-Ocular}, Month = {Nov}, Number = {6}, Pages = {395-407}, pmid = {14784863}, Pst = {ppublish}, Title = {The elementary vestibulo-ocular reflex arc}, Volume = {13}, Year = {1950}} @article{Collewijn:1977, Abstract = {1. Eye- and head movements were recorded in unrestrained, spontaneously behaving rabbits with a new technique, based upon phase detection of signals induced in implanted coils by a rotating magnetic field. 2. Movements of the eye in space were exclusively saccadic. In the intersaccadic intervals the eyes were stabilized in space, even during vigorous head movements. Most of this stability was maintained in darkness, except for the occurrence of slow drift. 3. Many saccades were initiated while the head was stationary. They were accompanied by a similar, but slower head rotation with approximately the same amplitude. The displacement of the eye in space was a pure step without appreciable under- or over-shoot. The deviation of the eye in the head was mostly transient. 4. Other saccades were started while the head was moving and were possibly fast phases of a vestibulo-ocular reflex. The time course of the eye movement in space was identical for all saccades, whether the head was moving prior to the saccade or not. Eye movements without any head movement were not observed. 5. Saccades were mostly large (average 20-6 +/- 12-4 degrees S.D.) and never smaller than 1 degree. The relations of maximal velocity and duration to amplitude were similar to those reported for man. 6. Visual pursuit of moving objects, when elicited, was only saccadic and never smooth. 7. It is concluded that the co-ordination and dynamics of the rabbit's head- and eye movements are similar to those of primates. In the absence of foveal specilization, the eye movements are restricted to a rather global redirection of the visual field, possibly in particular of the binocular area.}, Author = {Collewijn, H}, Date-Added = {2017-10-27 18:14:06 +0000}, Date-Modified = {2017-10-27 18:14:06 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Animals; Behavior, Animal; Eye Movements; Head; Movement; Rabbits; Saccades; Time Factors; Vision, Ocular}, Month = {Apr}, Number = {2}, Pages = {471-98}, Pmc = {PMC1283576}, pmid = {857007}, Pst = {ppublish}, Title = {Eye- and head movements in freely moving rabbits}, Volume = {266}, Year = {1977}} @article{Goldberg:1982, Abstract = {The eye movements produced by constant-speed rotations about an earth-horizontal axis (EHA) are similar in the alert squirrel monkey to those observed in other species. During EHA rotations, there are persistent eye movements, including a nonreversing nystagmus at lower rotation speeds and either a direction-reversing nystagmus or sinusoidal eye movements at higher rotation speeds. Horizontal eye movements are produced by "barbecue-spit" (yaw) rotations, vertical eye movements by "head-over-heels" (pitch) rotations. The responses can be viewed as composed of a bias component, reflected in the nonreversing nature of the nystagmus, and a cyclic component, reflected in the periodic modulation of slow-phase eye velocity as head position varies. Vestibular-nerve recordings in the barbiturate-anesthetized monkey indicate that neither semicircular-canal nor otolith afferents give rise to a directionally specific dc signal which can account for the bias component. Apparently the appropriate dc signal has to be constructed centrally from a sinusoidal or ac peripheral input. The otolith organs are a likely source of this peripheral input, although contributions from the semicircular canals and from somatosensory receptors must also be considered. Our results suggest that the directional information required to distinguish rotation direction, rather than being contained in the discharge of individual otolith afferents, is encoded across a population of afferents. Possible sources of such information are the phase differences in the sinusoidal responses of otolith afferents differing in their functional polarization vectors.}, Author = {Goldberg, J M and Fern{\'a}ndez, C}, Date-Added = {2017-10-27 18:07:26 +0000}, Date-Modified = {2017-10-27 18:07:26 +0000}, Journal = {Exp Brain Res}, Journal-Full = {Experimental brain research}, Mesh = {Acoustic Maculae; Animals; Cebidae; Eye Movements; Motion Perception; Neurons, Afferent; Rotation; Saimiri; Semicircular Canals; Vestibular Nerve}, Number = {3}, Pages = {393-402}, pmid = {6124447}, Pst = {ppublish}, Title = {Eye movements and vestibular-nerve responses produced in the squirrel monkey by rotations about an earth-horizontal axis}, Volume = {46}, Year = {1982}} @article{McMullen:2004, Abstract = {Previous studies have suggested that abnormal visual experience early in life induces ocular motor abnormalities. The purpose of this study was to determine how visual deprivation alters the function and gene expression profile of the ocular motor system in mice. We measured the effect of dark rearing on eye movements, gene expression in the oculomotor nucleus, and contractility of isolated extraocular muscles. In vivo eye movement recordings showed decreased gains for optokinetic and vestibulo-ocular reflexes, confirming an effect of dark rearing on overall ocular motor function. Saccade peak velocities were preserved, however, arguing that the quantitative changes in these reflexes were not secondary to limitations in force generation. Using microarrays and quantitative PCR, we found that dark rearing shifted the oculomotor nucleus transcriptome to a state of delayed/arrested development. The expression of 132 genes was altered by dark rearing; these genes fit in various functional categories (signal transduction, transcription/translation control, metabolism, synaptic function, cytoskeleton), and some were known to be associated with neuronal development and plasticity. Extraocular muscle contractility was impaired by dark rearing to a greater extent than expected from the in vivo ocular motility studies: changes included decreased force and shortening speed and evidence of abnormal excitability. The results indicate that normal development of the mouse ocular motor system and its muscles requires visual experience. The transcriptional pattern of arrested development may indicate that vision is required to establish the adult pattern, but it also may represent the plastic response of oculomotor nuclei to abnormal extraocular muscles.}, Author = {McMullen, Colleen A and Andrade, Francisco H and Stahl, John S}, Date-Added = {2017-10-27 17:29:25 +0000}, Date-Modified = {2017-10-27 17:29:25 +0000}, Doi = {10.1523/JNEUROSCI.3234-03.2004}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Animals, Newborn; Darkness; Eye Movements; Gene Expression Profiling; Genomics; Mesencephalon; Mice; Mice, Inbred C57BL; Motor Neurons; Oculomotor Muscles; Sensory Deprivation}, Month = {Jan}, Number = {1}, Pages = {161-9}, pmid = {14715949}, Pst = {ppublish}, Title = {Functional and genomic changes in the mouse ocular motor system in response to light deprivation from birth}, Volume = {24}, Year = {2004}, url = {papers/McMullen_JNeurosci2004.pdf}} @article{Hyvarinen:2000, Abstract = {A fundamental problem in neural network research, as well as in many other disciplines, is finding a suitable representation of multivariate data, i.e. random vectors. For reasons of computational and conceptual simplicity, the representation is often sought as a linear transformation of the original data. In other words, each component of the representation is a linear combination of the original variables. Well-known linear transformation methods include principal component analysis, factor analysis, and projection pursuit. Independent component analysis (ICA) is a recently developed method in which the goal is to find a linear representation of non-Gaussian data so that the components are statistically independent, or as independent as possible. Such a representation seems to capture the essential structure of the data in many applications, including feature extraction and signal separation. In this paper, we present the basic theory and applications of ICA, and our recent work on the subject.}, Author = {Hyv{\"a}rinen, A and Oja, E}, Date = {2000 May-Jun}, Date-Added = {2017-10-26 21:29:59 +0000}, Date-Modified = {2017-10-26 21:29:59 +0000}, Journal = {Neural Netw}, Journal-Full = {Neural networks : the official journal of the International Neural Network Society}, Mesh = {Algorithms; Artifacts; Brain; Humans; Magnetoencephalography; Neural Networks (Computer); Normal Distribution}, Number = {4-5}, Pages = {411-30}, pmid = {10946390}, Pst = {ppublish}, Title = {Independent component analysis: algorithms and applications}, Volume = {13}, Year = {2000}, url = {papers/Hyvärinen_NeuralNetw2000.pdf}} @article{Chase:1945, Author = {Chase, H B}, Date-Added = {2017-10-26 20:12:11 +0000}, Date-Modified = {2017-10-26 20:13:46 +0000}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {BRAIN/anatomy and histology; EYES/abnormalities}, Mesh = {Animals; Brain; Cranial Nerves; Eye Abnormalities; Mice}, Month = {Oct}, Pages = {121-39}, pmid = {21004976}, Pst = {ppublish}, Title = {Studies on an anophthalmic strain of mice; associated cranial nerves and brain centers}, Volume = {83}, Year = {1945}, url = {papers/CHASE_JCompNeurol1945.pdf}} @article{Vokoun:2010, Abstract = {The superior colliculus (SC) is a midbrain structure that plays a role in converting sensation into action. Most SC research focuses on either in vivo extracellular recordings from behaving monkeys or patch-clamp recordings from smaller mammals in vitro. However, the activity of neuronal circuits is necessary to generate behavior, and neither of these approaches measures the simultaneous activity of large populations of neurons that make up circuits. Here, we describe experiments in which we measured changes in membrane potential across the SC map using voltage imaging of the rat SC in vitro. Our results provide the first high temporal and spatial resolution images of activity within the SC. Electrical stimulation of the SC evoked a characteristic two-component optical response containing a short latency initial-spike and a longer latency after-depolarization. Single-pulse stimulation in the superficial SC evoked a pattern of intralaminar and interlaminar spread that was distinct from the spread evoked by the same stimulus applied to the intermediate SC. Intermediate layer stimulation produced a more extensive and more ventrally located activation of the superficial layers than did stimulation in the superficial SC. Together, these results indicate the recruitment of dissimilar subpopulations of circuitry depending on the layer stimulated. Field potential recordings, pharmacological manipulations, and timing analyses indicate that the patterns of activity were physiologically relevant and largely synaptically driven. Therefore, voltage imaging is a powerful technique for the study of spatiotemporal dynamics of electrical signaling across neuronal populations, providing insight into neural circuits that underlie behavior.}, Author = {Vokoun, Corinne R and Jackson, Meyer B and Basso, Michele A}, Date-Added = {2017-10-26 19:57:19 +0000}, Date-Modified = {2017-10-26 19:57:19 +0000}, Doi = {10.1523/JNEUROSCI.1387-10.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {2-Amino-5-phosphonovalerate; Action Potentials; Anesthetics, Local; Animals; Bicuculline; Biophysical Phenomena; Brain Mapping; Diagnostic Imaging; Electric Stimulation; Evoked Potentials; Excitatory Amino Acid Antagonists; GABA Antagonists; In Vitro Techniques; Neural Conduction; Neural Pathways; Quinoxalines; Rats; Rats, Sprague-Dawley; Reaction Time; Superior Colliculi; Synapses; Tetrodotoxin}, Month = {Aug}, Number = {32}, Pages = {10667-82}, pmid = {20702698}, Pst = {ppublish}, Title = {Intralaminar and interlaminar activity within the rodent superior colliculus visualized with voltage imaging}, Volume = {30}, Year = {2010}, url = {papers/Vokoun_JNeurosci2010.pdf}} @article{Bosman:2011, Abstract = {The rodent whisker system is widely used as a model system for investigating sensorimotor integration, neural mechanisms of complex cognitive tasks, neural development, and robotics. The whisker pathways to the barrel cortex have received considerable attention. However, many subcortical structures are paramount to the whisker system. They contribute to important processes, like filtering out salient features, integration with other senses, and adaptation of the whisker system to the general behavioral state of the animal. We present here an overview of the brain regions and their connections involved in the whisker system. We do not only describe the anatomy and functional roles of the cerebral cortex, but also those of subcortical structures like the striatum, superior colliculus, cerebellum, pontomedullary reticular formation, zona incerta, and anterior pretectal nucleus as well as those of level setting systems like the cholinergic, histaminergic, serotonergic, and noradrenergic pathways. We conclude by discussing how these brain regions may affect each other and how they together may control the precise timing of whisker movements and coordinate whisker perception.}, Author = {Bosman, Laurens W J and Houweling, Arthur R and Owens, Cullen B and Tanke, Nouk and Shevchouk, Olesya T and Rahmati, Negah and Teunissen, Wouter H T and Ju, Chiheng and Gong, Wei and Koekkoek, Sebastiaan K E and De Zeeuw, Chris I}, Date-Added = {2017-10-25 19:57:33 +0000}, Date-Modified = {2017-10-25 19:57:33 +0000}, Doi = {10.3389/fnint.2011.00053}, Journal = {Front Integr Neurosci}, Journal-Full = {Frontiers in integrative neuroscience}, Keywords = {anatomy; barrel cortex; basal ganglia; cerebellum; follicle--sinus complex; rhythmic movements; sensorimotor integration; vibrissa}, Pages = {53}, Pmc = {PMC3207327}, pmid = {22065951}, Pst = {epublish}, Title = {Anatomical pathways involved in generating and sensing rhythmic whisker movements}, Volume = {5}, Year = {2011}, url = {papers/Bosman_FrontIntegrNeurosci2011.pdf}} @article{Berzhanskaya:2017, Abstract = {Children with Fragile X syndrome (FXS) have deficits of attention and arousal. To begin to identify the neural causes of these deficits, we examined juvenile rats lacking the Fragile X mental retardation protein (FMR-KO) for disruption of cortical activity related to attention and arousal. Specifically, we examined the switching of visual cortex between activated and inactivated states that normally occurs during movement and quiet rest, respectively. In both wild-type and FMR-KO rats, during the third and fourth postnatal weeks cortical activity during periods of movement was dominated by an activated state with prominent 18-52 Hz activity. However, during quiet rest, when activity in wild-type rats became dominated by the inactivated state (3-9 Hz activity), FMR-KO rat cortex abnormally remained activated, resulting in increased high-frequency and reduced low-frequency power during rest. Firing rate correlations revealed reduced synchronization in FMR-KO rats, particularly between fast-spiking interneurons, that developmentally precede cortical state defects. Together our data suggest that disrupted inhibitory connectivity impairs the ability of visual cortex to regulate exit from the activated state in a behaviorally appropriate manner, potentially contributing to disrupted attention and sensory processing observed in children with FXS by making it more difficult to decrease cortical drive by unattended stimuli.}, Author = {Berzhanskaya, Julia and Phillips, Marnie A and Gorin, Alexis and Lai, Chongxi and Shen, Jing and Colonnese, Matthew T}, Date-Added = {2017-10-19 20:15:03 +0000}, Date-Modified = {2017-10-19 20:15:03 +0000}, Doi = {10.1093/cercor/bhv331}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {EEG; attention; autism; cortex; development}, Month = {Feb}, Number = {2}, Pages = {1386-1400}, pmid = {26733529}, Pst = {ppublish}, Title = {Disrupted Cortical State Regulation in a Rat Model of Fragile X Syndrome}, Volume = {27}, Year = {2017}, url = {papers/Berzhanskaya_CerebCortex2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhv331}} @article{Murata:2016, Abstract = {Spontaneous retinal waves are critical for the development of receptive fields in visual thalamus (LGN) and cortex (VC). Despite a detailed understanding of the circuit specializations in retina that generate waves, whether central circuit specializations also exist to control their propagation through visual pathways of the brain is unknown. Here we identify a developmentally transient, corticothalamic amplification of retinal drive to thalamus as a mechanism for retinal wave transmission in the infant rat brain. During the period of retinal waves, corticothalamic connections excite LGN, rather than driving feedforward inhibition as observed in the adult. This creates an excitatory feedback loop that gates retinal wave transmission through the LGN. This cortical multiplication of retinal wave input ends just prior to eye-opening, as cortex begins to inhibit LGN. Our results show that the early retino-thalamo-cortical circuit uses developmentally specialized feedback amplification to ensure powerful, high-fidelity transmission of retinal activity despite immature connectivity.}, Author = {Murata, Yasunobu and Colonnese, Matthew T}, Date-Added = {2017-10-19 20:11:24 +0000}, Date-Modified = {2017-10-19 20:11:24 +0000}, Doi = {10.7554/eLife.18816}, Journal = {Elife}, Journal-Full = {eLife}, Keywords = {EEG; activity depedent development; neuroscience; oscillations; plasticity; rat; retinal waves}, Month = {Oct}, Pmc = {PMC5059135}, pmid = {27725086}, Pst = {epublish}, Title = {An excitatory cortical feedback loop gates retinal wave transmission in rodent thalamus}, Volume = {5}, Year = {2016}, url = {papers/Murata_Elife2016.pdf}, Bdsk-File-2 = {papers/Murata_Elife2016a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.7554/eLife.18816}} @article{Shen:2016, Abstract = {A comprehensive developmental timeline of activity in the mouse cortex in vivo is lacking. Understanding the activity changes that accompany synapse and circuit formation is important to understand the mechanisms by which activity molds circuits and would help to identify critical checkpoints for normal development. To identify key principles of cortical activity maturation, we systematically tracked spontaneous and sensory-evoked activity with extracellular recordings of primary visual cortex (V1) in nonanesthetized mice. During the first postnatal week (postnatal days P4-P7), V1 was not visually responsive and exhibited long (>10 s) periods of network silence. Activation consisted exclusively of "slow-activity transients," 2-10 s periods of 6-10 Hz "spindle-burst' oscillations; the response to spontaneous retinal waves. By tracking daily changes in this activity, two key components of spontaneous activity maturation were revealed: (1) spindle-burst frequency acceleration (eventually becoming the 20-50 Hz broadband activity caused by the asynchronous state) and (2) "filling-in" of silent periods with low-frequency (2-4 Hz) activity (beginning on P10 and complete by P13). These two changes are sufficient to create the adult-like pattern of continuous activity, alternation between fast-asynchronous and slow-synchronous activity, by eye opening. Visual responses emerged on P8 as evoked spindle-bursts and neuronal firing with a signal-to-noise ratio higher than adult. Both were eliminated by eye opening, leaving only the mature, short-latency response. These results identify the developmental origins of mature cortical activity and implicate the period before eye opening as a critical checkpoint. By providing a systematic description of electrical activity development, we establish the murine visual cortex as a model for the electroencephalographic development of fetal humans. SIGNIFICANCE STATEMENT: Cortical activity is an important indicator of long-term health and survival in preterm infants and molds circuit formation, but gaps remain in our understanding of the origin and normal progression of this activity in the developing cortex. We aimed to rectify this by monitoring daily changes in cortical activity in the nonanesthetized mouse, an important preclinical model of disease and development. At ages approximately equivalent to normal human term birth, mouse cortex exhibits primarily network silence, with spontaneous "spindle bursts" as the only form of activity. In contrast, mature cortex is noisy, alternating between asynchronous/discontinuous and synchronous/continuous states. This work identifies the key processes that produce this maturation and provides a normative reference for murine-based studies of cortical circuit development.}, Author = {Shen, Jing and Colonnese, Matthew T}, Date-Added = {2017-10-19 20:04:18 +0000}, Date-Modified = {2017-10-19 20:04:18 +0000}, Doi = {10.1523/JNEUROSCI.1903-16.2016}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {EEG; mouse; spindle-burst; spontaneous activity}, Mesh = {Action Potentials; Aging; Animals; Animals, Newborn; Biological Clocks; Mice; Mice, Inbred C57BL; Nerve Net; Neurogenesis; Visual Cortex; Visual Perception}, Month = {Nov}, Number = {48}, Pages = {12259-12275}, Pmc = {PMC5148222}, pmid = {27903733}, Pst = {ppublish}, Title = {Development of Activity in the Mouse Visual Cortex}, Volume = {36}, Year = {2016}, url = {papers/Shen_JNeurosci2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1903-16.2016}} @article{Colonnese:2017, Abstract = {Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column. To study this we used single-shank multi-electrode array recordings of spontaneous activity in the visual cortex of non-anesthetized neonatal mice to quantify single-unit firing rates, and applied multiple measures of network interaction and synchrony throughout the period of map formation and immediately after eye-opening. We find that despite co-modulation of firing rates on a slow time scale (hundreds of ms), the number of coactive neurons, as well as pair-wise neural spike-rate correlations, are both lower before eye-opening. In fact, on post-natal days (P)6-9 correlated activity was lower than expected by chance, suggesting active decorrelation of activity during early bursts. Neurons in lateral geniculate nucleus developed in an opposite manner, becoming less correlated after eye-opening. Population coupling, a measure of integration in the local network, revealed a population of neurons with particularly strong local coupling present at P6-11, but also an adult-like diversity of coupling at all ages, suggesting that a neuron's identity as locally or distally coupled is determined early. The occurrence probabilities of unique neuronal "words" were largely similar at all ages suggesting that retinal waves drive adult-like patterns of co-activation. These findings suggest that the bursts of spontaneous activity during early visual development do not drive hyper-synchronous activity within columns. Rather, retinal waves provide windows of potential activation during which neurons are active but poorly correlated, adult-like patterns of correlation are achieved soon after eye-opening.}, Author = {Colonnese, Matthew T and Shen, Jing and Murata, Yasunobu}, Date-Added = {2017-10-19 20:02:41 +0000}, Date-Modified = {2017-10-19 20:02:41 +0000}, Doi = {10.3389/fncel.2017.00289}, Journal = {Front Cell Neurosci}, Journal-Full = {Frontiers in cellular neuroscience}, Keywords = {development; oscillation; retinal wave; spindle-burst; spontaneous activity; synchronization; visual cortex}, Pages = {289}, Pmc = {PMC5611364}, pmid = {28979189}, Pst = {epublish}, Title = {Uncorrelated Neural Firing in Mouse Visual Cortex during Spontaneous Retinal Waves}, Volume = {11}, Year = {2017}, url = {papers/Colonnese_FrontCellNeurosci2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncel.2017.00289}} @article{Berger:1997, Abstract = {To examine the involvement of supraspinal inputs in the maturation of motor activity patterns in the developing fetal lamb, we recorded spontaneous electromyographic activity from spinally innervated muscles at approximately 45, 65, and 95 days gestation (G45, G65, and G95; term = 147 days). At G45, fetal activity occurred in synchronized activity-inactivity cycles of approximately 2 min duration, with the activity phase lasting 22.2 +/- 4.8 s and the inactivity phase lasting 95.4 +/- 13.3 s (mean +/- standard error of the mean, n = 5). At G65 and G95, the organization of activity was clearly different from that at G45 in that it was no longer cyclic, nor was the discharge of different muscles synchronized. By contrast, after spinal cord transection at G62, synchronised cyclic activity occurred in muscles innervated by segmental levels below the transection, both at G65 and G95. At G65 the duration of the activity phase of the cycle was 53.5 +/- 6.0 s, while the inactivity phase lasted 171.6 +/- 22.1 s; these durations did not alter between G65 and G95. Since spinal cord transection leads to the motor behavior of the G65 fetus reverting to the cyclic pattern characteristic of the G45 fetus, we conclude that supraspinal inputs begin to modulate the output of the spinal pattern generators at some stage between G45 and G65. The observation that spinally transected fetuses generate identical behavior at G65 and G95, both in terms of its cyclic character and the duration of cycles, suggests that spinal circuits undergo little autonomous development over this period; that is, the altered behavior observed in the developing intact fetus reflects the influence of supraspinal inputs on the motor circuits of the spinal cord.}, Author = {Berger, P J and Kyriakides, M A and Cooke, I R}, Date-Added = {2017-10-09 20:59:20 +0000}, Date-Modified = {2017-10-09 20:59:20 +0000}, Journal = {J Neurobiol}, Journal-Full = {Journal of neurobiology}, Mesh = {Animals; Behavior, Animal; Diaphragm; Electromyography; Extremities; Female; Fetus; Motor Activity; Muscle Denervation; Muscle, Skeletal; Neurons, Efferent; Peripheral Nervous System; Pregnancy; Sheep; Spinal Cord}, Month = {Sep}, Number = {3}, Pages = {276-88}, pmid = {9298765}, Pst = {ppublish}, Title = {Supraspinal influence on the development of motor behavior in the fetal lamb}, Volume = {33}, Year = {1997}, url = {papers/Berger_JNeurobiol1997.pdf}} @article{Zhang:2012, Abstract = {Self-avoidance is a mechanism by which dendrites from the same neuron repel one another in order to establish uniform coverage of the dendritic field. The importance of self-avoidance for the development of complex arborization patterns has been highlighted by studies of Drosophila sensory and mouse retinal neurons. However, it is unclear whether branch patterning in the mammalian central nervous system is also governed by this strategy. We reduced Satb2 expression in a population of layer II/III pyramidal neurons in vivo by RNA interference and found that the somas of Satb2-deficient neurons clumped together, and their dendrites failed to expand laterally but instead formed fascicles. Furthermore, experiments showed that reducing Satb2 caused the adhesion of not only neighboring Satb2-deficient neurons but also neighboring wild-type neurons. Our results indicate a cell autonomous and non-cell autonomous role for Satb2 in regulating the adhesive and/or repulsive properties of cerebral pyramidal neurons.}, Author = {Zhang, Lei and Song, Ning-Ning and Chen, Jia-Yin and Huang, Ying and Li, He and Ding, Yu-Qiang}, Date-Added = {2017-07-05 17:41:29 +0000}, Date-Modified = {2017-07-05 17:41:29 +0000}, Doi = {10.1093/cercor/bhr215}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Animals, Newborn; Cell Adhesion; Cell Communication; Cell Enlargement; Cells, Cultured; Dendrites; Matrix Attachment Region Binding Proteins; Mice; Pyramidal Cells; Transcription Factors}, Month = {Jul}, Number = {7}, Pages = {1510-9}, pmid = {21885532}, Pst = {ppublish}, Title = {Satb2 is required for dendritic arborization and soma spacing in mouse cerebral cortex}, Volume = {22}, Year = {2012}, url = {papers/Zhang_CerebCortex2012.pdf}} @article{McCaig:2005, Abstract = {Direct-current (DC) electric fields are present in all developing and regenerating animal tissues, yet their existence and potential impact on tissue repair and development are largely ignored. This is primarily due to ignorance of the phenomenon by most researchers, some technically poor early studies of the effects of applied fields on cells, and widespread misunderstanding of the fundamental concepts that underlie bioelectricity. This review aims to resolve these issues by describing: 1) the historical context of bioelectricity, 2) the fundamental principles of physics and physiology responsible for DC electric fields within cells and tissues, 3) the cellular mechanisms for the effects of small electric fields on cell behavior, and 4) the clinical potential for electric field treatment of damaged tissues such as epithelia and the nervous system.}, Author = {McCaig, Colin D and Rajnicek, Ann M and Song, Bing and Zhao, Min}, Date-Added = {2017-07-05 17:39:21 +0000}, Date-Modified = {2017-07-05 17:39:21 +0000}, Doi = {10.1152/physrev.00020.2004}, Journal = {Physiol Rev}, Journal-Full = {Physiological reviews}, Mesh = {Animals; Cell Physiological Phenomena; Central Nervous System; Electromagnetic Fields; Electrophysiology; Embryo, Mammalian; Female; Humans; Pregnancy}, Month = {Jul}, Number = {3}, Pages = {943-78}, pmid = {15987799}, Pst = {ppublish}, Title = {Controlling cell behavior electrically: current views and future potential}, Volume = {85}, Year = {2005}, url = {papers/McCaig_PhysiolRev2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/physrev.00020.2004}} @article{Neafsey:1986, Abstract = {In conclusion, the rat primary motor cortex appears to be organized into irregularly shaped patches of cortex devoted to particular movements. The location of major subdivisions such as the forelimb or hindlimb areas is somatotopic and is consistent from animal to animal, but the internal organization of the pattern of movements represented within major subdivisions varies significantly between animals. The motor cortex includes both agranular primary motor cortex (AgL) and, in addition, a significant amount of the bordering granular somatic sensory cortex (Gr(SI)), as well as the rostral portion of the taste sensory insular or claustrocortex (Cl). The rat frontal cortex also contains a second, rostral motor representation of the forelimb, trunk and hindlimb, which is somatotopically organized and may be the rat's supplementary motor area. Both of these motor representations give rise to direct corticospinal projections, some of which may make monosynaptic connections with cervical enlargement motoneurons. Medial to the primary motor cortex, in cytoarchitectonic field AgM, is what appears to be part of the rat's frontal eye fields, a region which also includes the vibrissae motor representation. The somatic motor cortical output organization pattern in the rat is remarkably similar to that seen in the primate, whose primary, supplementary and frontal eye field cortical motor regions have been extensively studied.}, Author = {Neafsey, E J and Bold, E L and Haas, G and Hurley-Gius, K M and Quirk, G and Sievert, C F and Terreberry, R R}, Date-Added = {2017-06-13 17:30:19 +0000}, Date-Modified = {2017-06-13 17:32:40 +0000}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {topographic map; microstimulation; rodent; rat; Somatosensory Cortex; Neocortex}, Mesh = {Animals; Brain Mapping; Electric Stimulation; Forelimb; Hindlimb; Lip; Mandible; Motor Cortex; Rats; Somatosensory Cortex; Tongue; Vibrissae}, Month = {Mar}, Number = {1}, Pages = {77-96}, pmid = {3708387}, Pst = {ppublish}, Title = {The organization of the rat motor cortex: a microstimulation mapping study}, Volume = {396}, Year = {1986}, url = {papers/Neafsey_BrainRes1986.pdf}} @article{Belluzzi:2003, Abstract = {The subventricular zone produces neuroblasts that migrate to the olfactory bulb (OB) and differentiate into interneurons throughout postnatal life (Altman and Das, 1966; Hinds, 1968; Altman, 1969; Kishi et al., 1990; Luskin, 1993; Lois and Alvarez-Buylla, 1994). Although such postnatally generated interneurons have been characterized morphologically, their physiological differentiation has not been thoroughly described. Combining retroviral-mediated labeling of newly generated neurons with patch-clamp electrophysiology, we demonstrated that soon after new cells enter the layers of the olfactory bulb, they display voltage-dependent currents typical of more mature neurons. We also show that these "newcomers" express functional GABA and glutamate receptor channels, respond synaptically to stimulation of the olfactory nerve, and may establish both axodendritic and dendrodendritic synaptic contacts within the olfactory bulb. These data provide a basic description of the physiology of newly generated cells in the OB and show that such new cells are functional neurons that synaptically integrate into olfactory bulb circuitry soon after their arrival.}, Author = {Belluzzi, Ottorino and Benedusi, Mascia and Ackman, James and LoTurco, Joseph J}, Date-Added = {2017-05-31 23:30:38 +0000}, Date-Modified = {2017-05-31 23:32:18 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Potassium Channels/metabolism;Cell Differentiation;Electrophysiology/*methods;Animals;Stem Cells/cytology/physiology;Rats;Receptors, GABA/drug effects/metabolism;Interneurons/physiology/virology;Patch-Clamp Techniques;Female;Retroviridae/physiology;Rats, Wistar;Neurons/classification/*physiology/virology;Male;Olfactory Bulb/cytology/*physiology;01 Adult neurogenesis general;Luminescent Proteins/biosynthesis;Cell Lineage;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Receptors, Glutamate/drug effects/metabolism;Lateral Ventricles/cytology/physiology}, Mesh = {Animals; Cell Differentiation; Cell Lineage; Cell Movement; Delayed Rectifier Potassium Channels; Electrophysiology; Female; Green Fluorescent Proteins; Interneurons; Lateral Ventricles; Luminescent Proteins; Male; Neurons; Olfactory Bulb; Patch-Clamp Techniques; Potassium Channels; Potassium Channels, Voltage-Gated; Rats; Rats, Wistar; Receptors, GABA; Receptors, Glutamate; Retroviridae; Stem Cells}, Month = {Nov}, Number = {32}, Pages = {10411-8}, pmid = {14614100}, Pst = {ppublish}, Title = {Electrophysiological differentiation of new neurons in the olfactory bulb}, Volume = {23}, Year = {2003}, url = {papers/Belluzzi_JNeurosci2003.pdf}} @article{Bai:2003, Abstract = {Mutations in the doublecortin gene (DCX) in humans cause malformation of the cerebral neocortex. Paradoxically, genetic deletion of Dcx in mice does not cause neocortical malformation. We used electroporation of plasmids encoding short hairpin RNA to create interference (RNAi) of DCX protein in utero, and we show that DCX is required for radial migration in developing rat neocortex. RNAi of DCX causes both cell-autonomous and non-cell autonomous disruptions in radial migration, and creates two disruptions in neocortical development. First, many neurons prematurely stop migrating to form subcortical band heterotopias within the intermediate zone and then white matter. Second, many neurons migrate into inappropriate neocortical lamina within normotopic cortex. In utero RNAi can therefore be effectively used to study the specific cellular roles of DCX in neocortical development and to produce an animal model of double cortex syndrome.}, Author = {Bai, Jilin and Ramos, Raddy L and Ackman, James B and Thomas, Ankur M and Lee, Richard V and LoTurco, Joseph J}, Date-Added = {2017-05-31 23:29:27 +0000}, Date-Modified = {2017-05-31 23:30:15 +0000}, Doi = {10.1038/nn1153}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Development;Female;Rats;Gene Deletion;Neuropeptides;Neocortex;RNA Interference;Rats, Wistar;Pregnancy;Animals, Newborn;Support, U.S. Gov't, P.H.S.;Animals;Cell Movement}, Mesh = {Animals; Animals, Newborn; Cell Movement; Female; Gene Deletion; Microtubule-Associated Proteins; Neocortex; Neuropeptides; Pregnancy; RNA Interference; Rats; Rats, Wistar}, Month = {Dec}, Number = {12}, Pages = {1277-83}, pmid = {14625554}, Pst = {ppublish}, Title = {RNAi reveals doublecortin is required for radial migration in rat neocortex}, Volume = {6}, Year = {2003}, url = {papers/Bai_NatNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1153}} @article{Pignatelli:2005, Author = {Pignatelli, Angela and Benedusi, Mascia and Ackman, James and Loturco, Joseph J and Belluzzi, Ottorino}, Date-Added = {2017-05-31 23:28:19 +0000}, Date-Modified = {2017-05-31 23:28:57 +0000}, Doi = {10.1093/chemse/bjh143}, Journal = {Chem Senses}, Journal-Full = {Chemical senses}, Keywords = {Adult neurogenesis general}, Mesh = {Animals; Cell Movement; Chlorides; Green Fluorescent Proteins; Humans; Juxtaglomerular Apparatus; Kinetics; Mice; Models, Biological; Neurons; Olfactory Bulb}, Month = {Jan}, Pages = {i119-20}, pmid = {15738068}, Pst = {ppublish}, Title = {Functional properties of adult-born juxtaglomerular cells in the mammalian olfactory bulb}, Volume = {30 Suppl 1}, Year = {2005}, url = {papers/Pignatelli_ChemSenses2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/chemse/bjh143}} @article{Ackman:2006, Author = {Ackman, James B and LoTurco, Joseph J}, Date-Added = {2017-05-31 23:27:12 +0000}, Date-Modified = {2017-05-31 23:27:55 +0000}, Doi = {10.1016/j.expneurol.2006.03.007}, Journal = {Exp Neurol}, Journal-Full = {Experimental neurology}, Keywords = {01 Adult neurogenesis general;06 Adult neurogenesis injury induced;Hypoxia-Ischemia, Brain;Animals, Newborn;Animals;Humans;Cerebral Cortex;Neurons;review}, Mesh = {Animals; Animals, Newborn; Cerebral Cortex; Humans; Hypoxia-Ischemia, Brain; Neurons}, Month = {May}, Number = {1}, Pages = {5-9}, pmid = {16630614}, Pst = {ppublish}, Title = {The potential of endogenous neuronal replacement in developing cerebral cortex following hypoxic injury}, Volume = {199}, Year = {2006}, url = {papers/Ackman_ExpNeurol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2006.03.007}} @article{Ackman:2006a, Abstract = {The neurogenic potential of the postnatal neocortex has not been tested previously with a combination of both retroviral and bromodeoxyuridine (BrdU) labeling. Here we report that injections of enhanced green fluorescent protein (eGFP) retrovirus into 134 postnatal rats resulted in GFP labeling of 642 pyramidal neurons in neocortex. GFP-labeled neocortical pyramidal neurons, however, unlike GFP-labeled glia, did not incorporate BrdU. Closer inspection of retrovirally labeled neurons revealed microglia fused to the apical dendrites of labeled pyramidal neurons. Retroviral infection of mixed cultures of cortical neurons and glia confirmed the presence of specific neuronal-microglial fusions. Microglia did not fuse to other glial cell types, and cultures not treated with retrovirus lacked microglial-neuronal fusion. Furthermore, activation of microglia by lipopolysaccharide greatly increased the virally induced fusion of microglia to neurons in culture. These results indicate a novel form of specific cell fusion between neuronal dendrites and microglia and further illustrate the need for caution when interpreting evidence for neuronogenesis in the postnatal brain.}, Author = {Ackman, James B and Siddiqi, Faez and Walikonis, Randall S and LoTurco, Joseph J}, Date-Added = {2017-05-31 23:25:47 +0000}, Date-Modified = {2017-05-31 23:26:41 +0000}, Doi = {10.1523/JNEUROSCI.3340-06.2006}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Cell Fusion;research support, n.i.h., extramural ;Cell Communication;Rats;Pyramidal Cells;Retroviridae;Neocortex;Rats, Wistar;11 Glia;Microglia;Cells, Cultured;Animals;Retroviridae Infections;Neurons}, Mesh = {Animals; Cell Communication; Cell Fusion; Cells, Cultured; Microglia; Neocortex; Neurons; Pyramidal Cells; Rats; Rats, Wistar; Retroviridae; Retroviridae Infections}, Month = {Nov}, Number = {44}, Pages = {11413-22}, pmid = {17079670}, Pst = {ppublish}, Title = {Fusion of microglia with pyramidal neurons after retroviral infection}, Volume = {26}, Year = {2006}, url = {papers/Ackman_JNeurosci2006.pdf}, Bdsk-File-2 = {papers/Ackman_JNeurosci2006a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3340-06.2006}} @article{Ackman:2007, Abstract = {The dentate gyrus is a site of continual neurogenesis in the postnatal mammalian brain. Here we investigated postnatal neurogenesis in the citron kinase (citron-K) null-mutant rat (flathead). The flathead rat has substantial deficits in embryonic neurogenesis that are due to failed cytokinesis and cell death. We report here the loss of citron-K function has an even severer effect on postnatal neurogenesis in the dentate gyrus. Analysis of phosphorylated histone H3 expression in postnatal neurogenic regions of the flathead mutant revealed a complete lack of mitotic cells in the dentate gyrus and a large reduction in the number of dividing cells in the flathead subventricular zone. Examination of 5-bromodeoxyuridine incorporation in the flathead rat revealed that the flathead rat had a 99% reduction in the number of newly generated cells in the dentate gyrus at postnatal day 10. In addition, doublecortin-positive cells were essentially absent from the postnatal flathead dentate gyrus which also lacked the vimentin- and nestin-positive radial glia scaffold that defines the neurogenic niche in the postnatal subgranular zone. Together these results indicate that postnatal neurogenesis in the dentate gyrus is eliminated by loss of citron-K function, and suggests that a citron-K-dependent progenitor lineage forms the postnatal neuronal progenitor population in the dentate gyrus.}, Author = {Ackman, James B and Ramos, Raddy L and Sarkisian, Matthew R and Loturco, Joseph J}, Date-Added = {2017-05-31 23:23:49 +0000}, Date-Modified = {2017-05-31 23:25:01 +0000}, Doi = {10.1159/000096216}, Journal = {Dev Neurosci}, Journal-Full = {Developmental neuroscience}, Keywords = {research support, n.i.h., extramural;24 Pubmed search results 2008}, Mesh = {Animals; Cell Count; Cell Cycle Proteins; Cell Differentiation; Cell Proliferation; Dentate Gyrus; Disease Models, Animal; Gene Expression Regulation, Developmental; Histones; Intracellular Signaling Peptides and Proteins; Mitosis; Nervous System Malformations; Neurons; Protein-Serine-Threonine Kinases; Rats; Rats, Mutant Strains; Stem Cells}, Number = {1-2}, Pages = {113-23}, Pmc = {PMC2211714}, pmid = {17148954}, Pst = {ppublish}, Title = {Citron kinase is required for postnatal neurogenesis in the hippocampus}, Volume = {29}, Year = {2007}, url = {papers/Ackman_DevNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000096216}} @article{Allene:2008, Abstract = {Developing cortical networks generate a variety of coherent activity patterns that participate in circuit refinement. Early network oscillations (ENOs) are the dominant network pattern in the rodent neocortex for a short period after birth. These large-scale calcium waves were shown to be largely driven by glutamatergic synapses albeit GABA is a major excitatory neurotransmitter in the cortex at such early stages, mediating synapse-driven giant depolarizing potentials (GDPs) in the hippocampus. Using functional multineuron calcium imaging together with single-cell and field potential recordings to clarify distinct network dynamics in rat cortical slices, we now report that the developing somatosensory cortex generates first ENOs then GDPs, both patterns coexisting for a restricted time period. These patterns markedly differ by their developmental profile, dynamics, and mechanisms: ENOs are generated before cortical GDPs (cGDPs) by the activation of glutamatergic synapses mostly through NMDARs; cENOs are low-frequency oscillations (approximately 0.01 Hz) displaying slow kinetics and gradually involving the entire network. At the end of the first postnatal week, GABA-driven cortical GDPs can be reliably monitored; cGDPs are recurrent oscillations (approximately 0.1 Hz) that repetitively synchronize localized neuronal assemblies. Contrary to cGDPs, cENOs were unexpectedly facilitated by short anoxic conditions suggesting a contribution of glutamate accumulation to their generation. In keeping with this, alterations of extracellular glutamate levels significantly affected cENOs, which are blocked by an enzymatic glutamate scavenger. Moreover, we show that a tonic glutamate current contributes to the neuronal membrane excitability when cENOs dominate network patterns. Therefore, cENOs and cGDPs are two separate aspects of neocortical network maturation that may be differentially engaged in physiological and pathological processes.}, Author = {All{\`e}ne, Camille and Cattani, Adriano and Ackman, James B and Bonifazi, Paolo and Aniksztejn, Laurent and Ben-Ari, Yehezkel and Cossart, Rosa}, Date-Added = {2017-05-31 23:21:58 +0000}, Date-Modified = {2017-05-31 23:23:18 +0000}, Doi = {10.1523/JNEUROSCI.3733-08.2008}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology 21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology}, Mesh = {Animals; Animals, Newborn; Biological Clocks; Calcium Signaling; Cortical Synchronization; Extracellular Fluid; Glutamic Acid; Hypoxia, Brain; Membrane Potentials; Nerve Net; Neurogenesis; Organ Culture Techniques; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Somatosensory Cortex; Synapses; Synaptic Potentials; Synaptic Transmission; gamma-Aminobutyric Acid}, Month = {Nov}, Number = {48}, Pages = {12851-63}, pmid = {19036979}, Pst = {ppublish}, Title = {Sequential generation of two distinct synapse-driven network patterns in developing neocortex}, Volume = {28}, Year = {2008}, url = {papers/Allène_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3733-08.2008}} @article{Ackman:2009, Abstract = {In human patients, cortical dysplasia produced by Doublecortin (DCX) mutations lead to mental retardation and intractable infantile epilepsies, but the underlying mechanisms are not known. DCX(-/-) mice have been generated to investigate this issue. However, they display no neocortical abnormality, lessening their impact on the field. In contrast, in utero knockdown of DCX RNA produces a morphologically relevant cortical band heterotopia in rodents. On this preparation we have now compared the neuronal and network properties of ectopic, overlying, and control neurons in an effort to identify how ectopic neurons generate adverse patterns that will impact cortical activity. We combined dynamic calcium imaging and anatomical and electrophysiological techniques and report now that DCX(-/-)EGFP(+)-labeled ectopic neurons that fail to migrate develop extensive axonal subcortical projections and retain immature properties, and most of them display a delayed maturation of GABA-mediated signaling. Cortical neurons overlying the heterotopia, in contrast, exhibit a massive increase of ongoing glutamatergic synaptic currents reflecting a strong reactive plasticity. Neurons in both experimental fields are more frequently coactive in coherent synchronized oscillations than control cortical neurons. In addition, both fields displayed network-driven oscillations during evoked epileptiform burst. These results show that migration disorders produce major alterations not only in neurons that fail to migrate but also in their programmed target areas. We suggest that this duality play a major role in cortical dysfunction of DCX brains.}, Author = {Ackman, James B and Aniksztejn, Laurent and Cr{\'e}pel, Val{\'e}rie and Becq, H{\'e}l{\`e}ne and Pellegrino, Christophe and Cardoso, Carlos and Ben-Ari, Yehezkel and Represa, Alfonso}, Date-Added = {2017-05-31 23:19:57 +0000}, Date-Modified = {2017-05-31 23:21:14 +0000}, Doi = {10.1523/JNEUROSCI.4093-08.2009}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Dysplasia-heterotopia; 21 Neurophysiology}, Mesh = {Analysis of Variance; Animals; Animals, Genetically Modified; Animals, Newborn; Bicuculline; Cerebral Cortex; Disease Models, Animal; Electroporation; Excitatory Amino Acid Antagonists; Female; GABA Antagonists; Glutamate Decarboxylase; Glutamic Acid; Green Fluorescent Proteins; Humans; In Vitro Techniques; Malformations of Cortical Development; Membrane Potentials; Microtubule-Associated Proteins; Mutation; Nerve Net; Neurons; Neuropeptides; Pregnancy; Quinoxalines; RNA, Small Interfering; Rats; Rats, Wistar; Sodium Channel Blockers; Tetrodotoxin; Valine; gamma-Aminobutyric Acid}, Month = {Jan}, Number = {2}, Pages = {313-27}, pmid = {19144832}, Pst = {ppublish}, Title = {Abnormal network activity in a targeted genetic model of human double cortex}, Volume = {29}, Year = {2009}, url = {papers/Ackman_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4093-08.2009}} @article{Veinante:2003, Abstract = {In freely moving rats, whisking is associated with a slow modulation of neuronal excitability in the primary somatosensory cortex. Because it persists after the blockade of vibrissa input, it was suggested that the slow modulation might be mediated by motor-sensory corticocortical connections and perhaps result from the corollary discharges of corticofugal cells. In the present study, we identified motor cortical cells that project to the barrel field and reconstructed their axonal projections after juxtacellularly staining single cells with a biotinylated tracer. On the basis of the final destination of main axons, two groups of neurons contribute to motor-sensory projections: callosal cells (87.5%) and corticofugal cells (12.5%). Axon collaterals of callosal cells arborize in layers five to six of the granular and dysgranular zones and give off several branches that ascend between the barrels to ramify in the molecular layer. In contrast, the axon collaterals of corticofugal cells do not ramify in the infragranular layers but in layer 1. The origin of the majority of motor sensory projections from callosally projecting cells does not support the notion that the slow modulation results from the corollary discharges of corticofugal axons. It would rather originate from a separate population of cells, which could output the slow signal to the barrel field in parallel with the corticofugal commands to a brainstem pattern generator. As free whisking is characterized by bilateral concerted movements of the vibrissae, the transcallosal contribution of motor-sensory axons represents a substrate for synchronizing the slow modulation across both hemispheres.}, Author = {Veinante, Pierre and Desch{\^e}nes, Martin}, Date-Added = {2017-05-30 20:26:15 +0000}, Date-Modified = {2017-05-30 20:26:15 +0000}, Doi = {10.1002/cne.10769}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Axons; Biotin; Brain Mapping; Dextrans; Fluorescent Dyes; Motor Cortex; Neural Pathways; Neurons; Rats; Rats, Sprague-Dawley; Somatosensory Cortex; Vibrissae}, Month = {Sep}, Number = {1}, Pages = {98-103}, pmid = {12866130}, Pst = {ppublish}, Title = {Single-cell study of motor cortex projections to the barrel field in rats}, Volume = {464}, Year = {2003}, url = {papers/Veinante_JCompNeurol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10769}} @article{Wilson:1987, Abstract = {The neurons of origin of the bilateral corticostriatal projection arising from the medial agranular cortical field in rats were identified by antidromic activation from contralateral neostriatal stimulation. The same cells were tested for antidromic activation from the contralateral neocortex and for orthodromic responses to stimulation of neocortex of the contralateral hemisphere or ipsilateral rostral thalamus. The neurons were then stained by intracellular injection of horseradish peroxidase. The laminar distribution of these neurons was compared to that of cortical cells stained retrogradely after injection of wheat germ agglutinin/HRP in the ipsilateral or contralateral neostriatum. The morphological features of physiologically identified corticostriatal neurons, their laminar organization, and their responses to stimulation were examined and compared with crossed corticocortical and brainstem-projecting cells. Crossed corticostriatal cells of the medial agranular cortical field were medium-sized pyramidal neurons found in the superficial part of layer V and in the deep part of layer III. Their basilar dendritic fields and initial intracortical axon collateral arborizations were coextensive with the layer defined by the distribution of corticostriatal neurons. The apical dendrites were thin and sparsely branched but consistently reached layer I, where they made a small arborization. These morphological features were shared by cortical neurons projecting to contralateral neocortex but not responding antidromically to stimulation of contralateral neostriatum, but they were not shared by brainstem-projecting cortical cells. Orthodromic responses to contralateral cortical stimulation consisted of brief excitatory postsynaptic potentials that were followed by powerful and longer-lasting inhibitory postsynaptic potentials. Corticostriatal cells also exhibited small excitatory postsynaptic potentials in response to thalamic stimulation. Many crossed corticostriatal neurons were also commissural corticocortical neurons. The results of reciprocal collision tests showed that this was due to the existence of two separate axonal branches, one projecting to contralateral neocortex and one to contralateral neostriatum. Intracellular staining of these neurons revealed ipsilateral axonal projections to the neostriatum and cortex.}, Author = {Wilson, C J}, Date-Added = {2017-05-30 20:05:48 +0000}, Date-Modified = {2017-05-30 20:05:48 +0000}, Doi = {10.1002/cne.902630408}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Cerebral Cortex; Corpus Striatum; Male; Neural Pathways; Neurons; Rats; Rats, Inbred Strains; Synapses; Synaptic Transmission}, Month = {Sep}, Number = {4}, Pages = {567-80}, pmid = {2822779}, Pst = {ppublish}, Title = {Morphology and synaptic connections of crossed corticostriatal neurons in the rat}, Volume = {263}, Year = {1987}, url = {papers/Wilson_JCompNeurol1987.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902630408}} @article{Yorke:1975, Abstract = {Interhemispheric neocortical connections are widely distributed through the corpus callosum in the mouse. Callosal connections are present in all cytoarchitectonic fields except field 25. The distal extemity representations of SmI, and MsI the representation of the mystacial vibrissae in SmI, and the more peripheral field representation of VI are relatively acallosal. Dense projections lie in the midline or truncal representations of SmI, MsI, SmII, at the vertical meridian representations bordering field 17, and medial to the AI representation. The radial distribution of terminals is bimodal in most cytoarchitectonic fields. It is unimodal in the supracallosal segment of field 29b and fields 49 and 27, trimodal in fields 13 and 35. The cells of origin of callosal fibers appear to have the same topographic pattern of distribution as the callosal terminals, observing the same steep and gradual density gradients. No cells giving rise to callosal axons are identified in the acallosal regions of fields 2 and 17. Further, superficial focal lesions in cortical areas which receive callosal connections give rise only to homotopic contralateral degeneration. Acallosal areas of 17 and 2 give rise to no callosal connections. The cells of origin of callosal connections are located at all laminar levels of the cortex and include pyramidal and polymorphic cells but not the granule cells of layer IV.}, Author = {Yorke, Jr, C H and Caviness, Jr, V S}, Date-Added = {2017-05-30 19:53:12 +0000}, Date-Modified = {2017-05-30 19:53:12 +0000}, Doi = {10.1002/cne.901640206}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Corpus Callosum; Hybridization, Genetic; Mice; Mice, Inbred Strains; Neural Pathways; Peroxidases}, Month = {Nov}, Number = {2}, Pages = {233-45}, pmid = {1184784}, Pst = {ppublish}, Title = {Interhemispheric neocortical connections of the corpus callosum in the normal mouse: a study based on anterograde and retrograde methods}, Volume = {164}, Year = {1975}, url = {papers/Yorke_JCompNeurol1975.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901640206}} @article{Mitchell:2005, Abstract = {Integration of sensory-motor information in premotor cortex of rodents occurs largely through callosal and frontal cortical association projections directed in a hierarchically organized manner. Although most anatomical studies in rodents have been performed in rats, mammalian genetic models have focused on mice, because of their successful manipulation on the genetic and cell biological levels. It is therefore important to establish the normal patterns of anatomical connectivity in mice, which potentially differ from those in rats. The goal of this study is to investigate the anatomical development of callosal and frontal premotor projection neurons (CPN and FPN, respectively) in mouse sensory-motor and premotor cortex and to investigate quantitatively the potential laminar differences between these neurons with simultaneous callosal and frontal projections during development. The retrograde tracers Fluoro-Gold and DiI were injected into sensory-motor and premotor cortices, respectively, C57Bl/6 mice at different developmental times (P2, P8, P21, adult). We found that, in contrast to the case in primate and cat, there is widespread overlap in populations of long-distance projection neurons in mice; many projection neurons have simultaneous projections to both contralateral somatosensory cortex and ipsilateral frontal cortex, and a considerable number of these dual projections persist into adulthood. In addition, there are significant laminar differences in the percentage of neurons with simultaneous callosal and frontal projections, and an isolated population of layer V FPN has bilateral projections to both premotor cortical hemispheres. Taken together, our results indicate that a large proportion of individual projection neurons maintains simultaneous callosal and frontal projections in adult mice, suggesting that these dual projections might serve the critical function of integrating motor coordination information with multimodal association areas.}, Author = {Mitchell, Bartley D and Macklis, Jeffrey D}, Date-Added = {2017-05-30 19:27:20 +0000}, Date-Modified = {2017-05-30 19:28:22 +0000}, Doi = {10.1002/cne.20428}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {Adult neurogenesis general;Research Support, Non-U.S. Gov't;17 Transplant Regeneration;Motor Skills;Motor Cortex;Prefrontal Cortex;Research Support, U.S. Gov't, P.H.S.;Neural Pathways;Mice, Inbred C57BL;Cell Count;Nerve Net;Animals;Somatosensory Cortex;Mice;Neurons;Corpus Callosum}, Mesh = {Animals; Cell Count; Corpus Callosum; Mice; Mice, Inbred C57BL; Motor Cortex; Motor Skills; Nerve Net; Neural Pathways; Neurons; Prefrontal Cortex; Somatosensory Cortex}, Month = {Jan}, Number = {1}, Pages = {17-32}, pmid = {15612019}, Pst = {ppublish}, Title = {Large-scale maintenance of dual projections by callosal and frontal cortical projection neurons in adult mice}, Volume = {482}, Year = {2005}, url = {papers/Mitchell_JCompNeurol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20428}} @article{Greig:2013, Abstract = {The sophisticated circuitry of the neocortex is assembled from a diverse repertoire of neuronal subtypes generated during development under precise molecular regulation. In recent years, several key controls over the specification and differentiation of neocortical projection neurons have been identified. This work provides substantial insight into the 'molecular logic' underlying cortical development and increasingly supports a model in which individual progenitor-stage and postmitotic regulators are embedded within highly interconnected networks that gate sequential developmental decisions. Here, we provide an integrative account of the molecular controls that direct the progressive development and delineation of subtype and area identity of neocortical projection neurons.}, Author = {Greig, Luciano Custo and Woodworth, Mollie B and Galazo, Maria J and Padmanabhan, Hari and Macklis, Jeffrey D}, Date-Added = {2017-05-30 18:55:33 +0000}, Date-Modified = {2017-05-30 18:55:33 +0000}, Doi = {10.1038/nrn3586}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Biological Evolution; Gene Expression Regulation, Developmental; Humans; Mitosis; Neocortex; Nerve Net; Neural Pathways; Neural Stem Cells; Neurons}, Month = {Nov}, Number = {11}, Pages = {755-69}, Pmc = {PMC3876965}, pmid = {24105342}, Pst = {ppublish}, Title = {Molecular logic of neocortical projection neuron specification, development and diversity}, Volume = {14}, Year = {2013}, url = {papers/Greig_NatRevNeurosci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn3586}} @article{Molyneaux:2007, Abstract = {In recent years, tremendous progress has been made in understanding the mechanisms underlying the specification of projection neurons within the mammalian neocortex. New experimental approaches have made it possible to identify progenitors and study the lineage relationships of different neocortical projection neurons. An expanding set of genes with layer and neuronal subtype specificity have been identified within the neocortex, and their function during projection neuron development is starting to be elucidated. Here, we assess recent data regarding the nature of neocortical progenitors, review the roles of individual genes in projection neuron specification and discuss the implications for progenitor plasticity.}, Author = {Molyneaux, Bradley J and Arlotta, Paola and Menezes, Joao R L and Macklis, Jeffrey D}, Date-Added = {2017-05-30 18:40:15 +0000}, Date-Modified = {2017-05-30 18:40:15 +0000}, Doi = {10.1038/nrn2151}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Cell Differentiation; Cell Lineage; Cerebral Cortex; Efferent Pathways; Gene Expression Regulation, Developmental; Genes, Homeobox; Humans; Neuronal Plasticity; Neurons; Stem Cells}, Month = {Jun}, Number = {6}, Pages = {427-37}, pmid = {17514196}, Pst = {ppublish}, Title = {Neuronal subtype specification in the cerebral cortex}, Volume = {8}, Year = {2007}, url = {papers/Molyneaux_NatRevNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2151}} @article{Armentano:2007, Abstract = {We used cortex-specific deletion of the transcription factor gene COUP-TFI (also known as Nr2f1) in mice to demonstrate previously unknown fundamental roles for it in patterning mammalian neocortex into areas. The highest COUP-TFI expression is observed in the cortical progenitors and progeny in parietal and occipital cortex that form sensory areas, and the lowest expression was observed in frontal cortex that includes motor areas. Cortical deletion of COUP-TFI resulted in massive expansion of frontal areas, including motor, to occupy most of neocortex, paralleled by marked compression of sensory areas to caudal occipital cortex. These area patterning changes are preceded and paralleled by corresponding changes in molecular markers of area identity and altered axonal projections to maintain patterned area-specific input and output connections. We conclude that COUP-TFI is required for balancing patterning of neocortex into frontal/motor and sensory areas by acting in its expression domain to repress frontal/motor area identities and to specify sensory area identities.}, Author = {Armentano, Maria and Chou, Shen-Ju and Tomassy, Giulio Srubek and Leing{\"a}rtner, Axel and O'Leary, Dennis D M and Studer, Mich{\`e}le}, Date-Added = {2017-05-25 00:09:44 +0000}, Date-Modified = {2017-05-25 00:09:44 +0000}, Doi = {10.1038/nn1958}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Animals; Body Patterning; COUP Transcription Factor I; Embryo, Mammalian; Fibroblast Growth Factor 8; Gene Expression Regulation, Developmental; Homeodomain Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motor Cortex; Neural Pathways; PAX2 Transcription Factor; Serotonin; Somatosensory Cortex; Transcription Factors}, Month = {Oct}, Number = {10}, Pages = {1277-86}, pmid = {17828260}, Pst = {ppublish}, Title = {COUP-TFI regulates the balance of cortical patterning between frontal/motor and sensory areas}, Volume = {10}, Year = {2007}, url = {papers/Armentano_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1958}} @article{Yokoyama:2001, Abstract = {To investigate Eph-ephrin bidirectional signaling, a series of mutations were generated in the ephrin-B3 locus. The absence of both forward and reverse signaling resulted in mice with mirror movements as typified by a hopping locomotion. The corticospinal tract was defective as axons failed to respect the midline boundary of the spinal cord and bilaterally innervated both contralateral and ipsilateral motor neuron populations. A second mutation that expresses a truncated ephrin-B3 protein lacking its cytoplasmic domain did not lead to hopping, indicating that reverse signaling is not required for corticospinal innervation. Ephrin-B3 is concentrated at the spinal cord midline, while one of its receptors, EphA4, is expressed in postnatal corticospinal neurons as their fibers pathfind down the contralateral spinal cord. Our data indicate ephrin-B3 functions as a midline-anchored repellent to stimulate forward signaling in EphA4-expressing axons.}, Author = {Yokoyama, N and Romero, M I and Cowan, C A and Galvan, P and Helmbacher, F and Charnay, P and Parada, L F and Henkemeyer, M}, Date-Added = {2017-05-24 23:48:35 +0000}, Date-Modified = {2017-05-24 23:48:35 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Alleles; Animals; Axons; Electric Stimulation; Ephrin-B3; Female; Fetal Proteins; Gait Disorders, Neurologic; Homozygote; Male; Membrane Proteins; Mice; Mice, Neurologic Mutants; Motor Cortex; Mutagenesis, Site-Directed; Pyramidal Tracts; Receptor Protein-Tyrosine Kinases; Receptor, EphA4; Signal Transduction; Spinal Cord}, Month = {Jan}, Number = {1}, Pages = {85-97}, pmid = {11182083}, Pst = {ppublish}, Title = {Forward signaling mediated by ephrin-B3 prevents contralateral corticospinal axons from recrossing the spinal cord midline}, Volume = {29}, Year = {2001}, url = {papers/Yokoyama_Neuron2001.pdf}} @article{Dottori:1998, Abstract = {Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the EphA4 gene are viable and fertile but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like gait. Consistent with the observed phenotype, anatomical studies and anterograde tracing experiments reveal major disruptions of the corticospinal tract within the medulla and spinal cord in the null mutant animals. These results demonstrate a critical role for EphA4 in establishing the corticospinal projection.}, Author = {Dottori, M and Hartley, L and Galea, M and Paxinos, G and Polizzotto, M and Kilpatrick, T and Bartlett, P F and Murphy, M and K{\"o}ntgen, F and Boyd, A W}, Date-Added = {2017-05-24 23:42:32 +0000}, Date-Modified = {2017-05-24 23:42:32 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Base Sequence; Fetal Proteins; Gait; Gene Expression Regulation, Developmental; Genotype; Homozygote; Medulla Oblongata; Mice; Mice, Knockout; Molecular Sequence Data; Movement Disorders; Nerve Fibers; Nerve Tissue Proteins; Neural Pathways; Polymerase Chain Reaction; Receptor Protein-Tyrosine Kinases; Receptor, EphA4; Recombination, Genetic; Restriction Mapping; Spinal Cord; Stem Cells}, Month = {Oct}, Number = {22}, Pages = {13248-53}, Pmc = {PMC23772}, pmid = {9789074}, Pst = {ppublish}, Title = {EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract}, Volume = {95}, Year = {1998}, url = {papers/Dottori_ProcNatlAcadSciUSA1998.pdf}} @article{Kullander:2001, Abstract = {The EphA4 receptor tyrosine kinase regulates the formation of the corticospinal tract (CST), a pathway controlling voluntary movements, and of the anterior commissure (AC), connecting the neocortical temporal lobes. To study EphA4 kinase signaling in these processes, we generated mice expressing mutant EphA4 receptors either lacking kinase activity or with severely downregulated kinase activity. We demonstrate that EphA4 is required for CST formation as a receptor for which it requires an active kinase domain. In contrast, the formation of the AC is rescued by kinase-dead EphA4, suggesting that in this structure EphA4 acts as a ligand for which its kinase activity is not required. Unexpectedly, the cytoplasmic sterile-alpha motif (SAM) domain is not required for EphA4 functions. Our findings establish both kinase-dependent and kinase-independent functions of EphA4 in the formation of major axon tracts.}, Author = {Kullander, K and Mather, N K and Diella, F and Dottori, M and Boyd, A W and Klein, R}, Date-Added = {2017-05-24 23:39:19 +0000}, Date-Modified = {2017-05-24 23:39:19 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Axons; Brain Stem; Ephrin-A4; Ephrin-B2; Fetal Proteins; In Situ Hybridization; Membrane Proteins; Mice; Mice, Knockout; Mice, Mutant Strains; Molecular Sequence Data; Motor Cortex; Organ Specificity; Prosencephalon; Protein Structure, Tertiary; Pyramidal Tracts; RNA, Messenger; Receptor Protein-Tyrosine Kinases; Receptor, EphA4; Signal Transduction; Temporal Lobe}, Month = {Jan}, Number = {1}, Pages = {73-84}, pmid = {11182082}, Pst = {ppublish}, Title = {Kinase-dependent and kinase-independent functions of EphA4 receptors in major axon tract formation in vivo}, Volume = {29}, Year = {2001}, url = {papers/Kullander_Neuron2001.pdf}} @article{Leighton:2001, Abstract = {The search to understand the mechanisms regulating brain wiring has relied on biochemical purification approaches in vertebrates and genetic approaches in invertebrates to identify molecular cues and receptors for axon guidance. Here we describe a phenotype-based gene-trap screen in mice designed for the large-scale identification of genes controlling the formation of the trillions of connections in the mammalian brain. The method incorporates an axonal marker, which helps to identify cell-autonomous mechanisms in axon guidance, and has generated a resource of mouse lines with striking patterns of axonal labelling, which facilitates analysis of the normal wiring diagram of the brain. Studies of two of these mouse lines have identified an in vivo guidance function for a vertebrate transmembrane semaphorin, Sema6A, and have helped re-evaluate that of the Eph receptor EphA4.}, Author = {Leighton, P A and Mitchell, K J and Goodrich, L V and Lu, X and Pinson, K and Scherz, P and Skarnes, W C and Tessier-Lavigne, M}, Date-Added = {2017-05-24 22:51:25 +0000}, Date-Modified = {2017-05-24 22:51:25 +0000}, Doi = {10.1038/35065539}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Alkaline Phosphatase; Animals; Axons; Brain; Cell Adhesion Molecules, Neuronal; Cell Movement; Cells, Cultured; Female; Fetal Proteins; GPI-Linked Proteins; Genetic Techniques; Genetic Vectors; Humans; Isoenzymes; Male; Mice; Mice, Inbred C57BL; Mutation; Nerve Tissue Proteins; Neural Pathways; Neurons; Phenotype; Receptor Protein-Tyrosine Kinases; Receptor, EphA4; Ribosomes; Semaphorins; Sensory Receptor Cells; Thalamus}, Month = {Mar}, Number = {6825}, Pages = {174-9}, pmid = {11242070}, Pst = {ppublish}, Title = {Defining brain wiring patterns and mechanisms through gene trapping in mice}, Volume = {410}, Year = {2001}, url = {papers/Leighton_Nature2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35065539}} @article{Gallarda:2008, Abstract = {Execution of motor behaviors relies on circuitries effectively integrating immediate sensory feedback to efferent pathways controlling muscle activity. It remains unclear how, during neuromuscular circuit assembly, sensory and motor projections become incorporated into tightly coordinated, yet functionally separate pathways. We report that, within axial nerves, establishment of discrete afferent and efferent pathways depends on coordinate signaling between coextending sensory and motor projections. These heterotypic axon-axon interactions require motor axonal EphA3/EphA4 receptor tyrosine kinases activated by cognate sensory axonal ephrin-A ligands. Genetic elimination of trans-axonal ephrin-A --> EphA signaling in mice triggers drastic motor-sensory miswiring, culminating in functional efferents within proximal afferent pathways. Effective assembly of a key circuit underlying motor behaviors thus critically depends on trans-axonal signaling interactions resolving motor and sensory projections into discrete pathways.}, Author = {Gallarda, Benjamin W and Bonanomi, Dario and M{\"u}ller, Daniel and Brown, Arthur and Alaynick, William A and Andrews, Shane E and Lemke, Greg and Pfaff, Samuel L and Marquardt, Till}, Date-Added = {2017-05-24 22:50:00 +0000}, Date-Modified = {2017-05-24 22:50:00 +0000}, Doi = {10.1126/science.1153758}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Afferent Pathways; Animals; Axons; Cells, Cultured; Coculture Techniques; Efferent Pathways; Electrophysiology; Ephrins; Ganglia, Spinal; Growth Cones; Ligands; Mice; Mice, Transgenic; Motor Activity; Motor Neurons; Muscle, Skeletal; Mutation; Neurons, Afferent; Peripheral Nerves; Receptor, EphA3; Receptor, EphA4; Signal Transduction}, Month = {Apr}, Number = {5873}, Pages = {233-6}, Pmc = {PMC3158657}, pmid = {18403711}, Pst = {ppublish}, Title = {Segregation of axial motor and sensory pathways via heterotypic trans-axonal signaling}, Volume = {320}, Year = {2008}, url = {papers/Gallarda_Science2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1153758}} @article{Bedogni:2010, Abstract = {Areas and layers of the cerebral cortex are specified by genetic programs that are initiated in progenitor cells and then, implemented in postmitotic neurons. Here, we report that Tbr1, a transcription factor expressed in postmitotic projection neurons, exerts positive and negative control over both regional (areal) and laminar identity. Tbr1 null mice exhibited profound defects of frontal cortex and layer 6 differentiation, as indicated by down-regulation of gene-expression markers such as Bcl6 and Cdh9. Conversely, genes that implement caudal cortex and layer 5 identity, such as Bhlhb5 and Fezf2, were up-regulated in Tbr1 mutants. Tbr1 implements frontal identity in part by direct promoter binding and activation of Auts2, a frontal cortex gene implicated in autism. Tbr1 regulates laminar identity in part by downstream activation or maintenance of Sox5, an important transcription factor controlling neuronal migration and corticofugal axon projections. Similar to Sox5 mutants, Tbr1 mutants exhibit ectopic axon projections to the hypothalamus and cerebral peduncle. Together, our findings show that Tbr1 coordinately regulates regional and laminar identity of postmitotic cortical neurons.}, Author = {Bedogni, Francesco and Hodge, Rebecca D and Elsen, Gina E and Nelson, Branden R and Daza, Ray A M and Beyer, Richard P and Bammler, Theo K and Rubenstein, John L R and Hevner, Robert F}, Date-Added = {2017-05-24 20:46:48 +0000}, Date-Modified = {2017-05-24 20:46:48 +0000}, Doi = {10.1073/pnas.1002285107}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Biomarkers; DNA-Binding Proteins; Down-Regulation; Gene Expression Regulation, Developmental; Mice; Mitosis; Mutation; Neocortex; Neurons; Nuclear Proteins; Oligonucleotide Array Sequence Analysis; Organ Specificity; Protein Binding; Transcriptional Activation; Up-Regulation}, Month = {Jul}, Number = {29}, Pages = {13129-34}, Pmc = {PMC2919950}, pmid = {20615956}, Pst = {ppublish}, Title = {Tbr1 regulates regional and laminar identity of postmitotic neurons in developing neocortex}, Volume = {107}, Year = {2010}, url = {papers/Bedogni_ProcNatlAcadSciUSA2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1002285107}} @article{Kalil:2011, Abstract = {Precise wiring of cortical circuits during development depends upon axon extension, guidance, and branching to appropriate targets. Motile growth cones at axon tips navigate through the nervous system by responding to molecular cues, which modulate signaling pathways within axonal growth cones. Intracellular calcium signaling has emerged as a major transducer of guidance cues but exactly how calcium signaling pathways modify the actin and microtubule cytoskeleton to evoke growth cone behaviors and axon branching is still mysterious. Axons must often pause their extension in tracts while their branches extend into targets. Some evidence suggests a competition between growth of axons and branches but the mechanisms are poorly understood. Since it is difficult to study growing axons deep within the mammalian brain, much of what we know about signaling pathways and cytoskeletal dynamics of growth cones comes from tissue culture studies, in many cases, of non-mammalian species. Consequently it is not well understood how guidance cues relevant to mammalian neural development in vivo signal to the growth cone cytoskeleton during axon outgrowth and guidance. In this review we describe our recent work in dissociated cultures of developing rodent sensorimotor cortex in the context of the current literature on molecular guidance cues, calcium signaling pathways, and cytoskeletal dynamics that regulate growth cone behaviors. A major challenge is to relate findings in tissue culture to mechanisms of cortical development in vivo. Toward this goal, we describe our recent work in cortical slices, which preserve the complex cellular and molecular environment of the mammalian brain but allow direct visualization of growth cone behaviors and calcium signaling. Findings from this work suggest that mechanisms regulating axon growth and guidance in dissociated culture neurons also underlie development of cortical connectivity in vivo.}, Author = {Kalil, Katherine and Li, Li and Hutchins, B Ian}, Date-Added = {2017-05-23 05:43:57 +0000}, Date-Modified = {2017-05-23 05:43:57 +0000}, Doi = {10.3389/fnana.2011.00062}, Journal = {Front Neuroanat}, Journal-Full = {Frontiers in neuroanatomy}, Keywords = {CaMKII; Wnt5a; axon branching; axon guidance; axon outgrowth; calcium signaling; corpus callosum; microtubules}, Pages = {62}, Pmc = {PMC3202218}, pmid = {22046148}, Pst = {epublish}, Title = {Signaling mechanisms in cortical axon growth, guidance, and branching}, Volume = {5}, Year = {2011}, url = {papers/Kalil_FrontNeuroanat2011.pdf}} @article{Paul:2007, Abstract = {Agenesis of the corpus callosum (AgCC), a failure to develop the large bundle of fibres that connect the cerebral hemispheres, occurs in 1:4000 individuals. Genetics, animal models and detailed structural neuroimaging are now providing insights into the developmental and molecular bases of AgCC. Studies using neuropsychological, electroencephalogram and functional MRI approaches are examining the resulting impairments in emotional and social functioning, and have begun to explore the functional neuroanatomy underlying impaired higher-order cognition. The study of AgCC could provide insight into the integrated cerebral functioning of healthy brains, and may offer a model for understanding certain psychiatric illnesses, such as schizophrenia and autism.}, Author = {Paul, Lynn K and Brown, Warren S and Adolphs, Ralph and Tyszka, J Michael and Richards, Linda J and Mukherjee, Pratik and Sherr, Elliott H}, Date-Added = {2017-05-23 02:33:29 +0000}, Date-Modified = {2017-05-23 02:33:29 +0000}, Doi = {10.1038/nrn2107}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Child Behavior; Child, Preschool; Corpus Callosum; Developmental Disabilities; Female; Humans; Infant; Infant, Newborn; Mental Disorders; Neuropsychological Tests; Pregnancy}, Month = {Apr}, Number = {4}, Pages = {287-99}, pmid = {17375041}, Pst = {ppublish}, Title = {Agenesis of the corpus callosum: genetic, developmental and functional aspects of connectivity}, Volume = {8}, Year = {2007}, url = {papers/Paul_NatRevNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2107}} @article{Minshew:2007, Abstract = {This review covers a fraction of the new research developments in autism but establishes the basic elements of the new neurobiologic understanding of autism. Autism is a polygenetic developmental neurobiologic disorder with multiorgan system involvement, though it predominantly involves central nervous system dysfunction. The evidence supports autism as a disorder of the association cortex, both its neurons and their projections. In particular, it is a disorder of connectivity, which appears, from current evidence, to primarily involve intrahemispheric connectivity. The focus of connectivity studies thus far has been on white matter, but alterations in functional magnetic resonance imaging activation suggest that intracortical connectivity is also likely to be disturbed. Furthermore, the disorder has a broad impact on cognitive and neurologic functioning. Deficits in high-functioning individuals occur in processing that places high demands on integration of information and coordination of multiple neural systems. Intact or enhanced abilities share a dependence on low information-processing demands and local neural connections. This multidomain model with shared characteristics predicts an underlying pathophysiologic mechanism that impacts the brain broadly, according to a common neurobiologic principle. The multiorgan system involvement and diversity of central nervous system findings suggest an epigenetic mechanism.}, Author = {Minshew, Nancy J and Williams, Diane L}, Date-Added = {2017-05-23 02:28:39 +0000}, Date-Modified = {2017-05-23 02:28:39 +0000}, Doi = {10.1001/archneur.64.7.945}, Journal = {Arch Neurol}, Journal-Full = {Archives of neurology}, Mesh = {Autistic Disorder; Cerebral Cortex; Child; Diagnostic Imaging; Genetic Predisposition to Disease; Humans; Models, Neurological; Nerve Fibers, Myelinated; Nervous System Malformations; Neural Pathways; Neurons}, Month = {Jul}, Number = {7}, Pages = {945-50}, Pmc = {PMC2597785}, pmid = {17620483}, Pst = {ppublish}, Title = {The new neurobiology of autism: cortex, connectivity, and neuronal organization}, Volume = {64}, Year = {2007}, url = {papers/Minshew_ArchNeurol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1001/archneur.64.7.945}} @article{Fame:2011, Abstract = {Callosal projection neurons (CPN) are a diverse population of neocortical projection neurons that connect the two hemispheres of the cerebral cortex via the corpus callosum. They play key roles in high-level associative connectivity, and have been implicated in cognitive syndromes of high-level associative dysfunction, such as autism spectrum disorders. CPN evolved relatively recently compared to other cortical neuron populations, and have undergone disproportionately large expansion from mouse to human. While much is known about the anatomical trajectory of developing CPN axons, and progress has been made in identifying cellular and molecular controls over midline crossing, only recently have molecular-genetic controls been identified that specify CPN populations, and help define CPN subpopulations. In this review, we discuss the development, diversity and evolution of CPN.}, Author = {Fame, Ryann M and MacDonald, Jessica L and Macklis, Jeffrey D}, Date-Added = {2017-05-23 02:24:20 +0000}, Date-Modified = {2017-05-23 02:24:20 +0000}, Doi = {10.1016/j.tins.2010.10.002}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Mesh = {Animals; Cerebral Cortex; Corpus Callosum; Humans; Neurons}, Month = {Jan}, Number = {1}, Pages = {41-50}, Pmc = {PMC3053014}, pmid = {21129791}, Pst = {ppublish}, Title = {Development, specification, and diversity of callosal projection neurons}, Volume = {34}, Year = {2011}, url = {papers/Fame_TrendsNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2010.10.002}} @article{Garcez:2007, Abstract = {The main alternative output routes of adult cortical axons are the internal capsule and the corpus callosum. How do callosal axons choose their trajectories? We hypothesized that bifurcation followed by elimination of one branch is a developmental strategy for accomplishing this aim. Using embryonic and postnatal mice, we labelled cortical projecting neurons and quantified their axonal bifurcations in correlation with the mediolateral position of their somata. Bifurcating axons were numerous in the younger brains but declined during further development. Most bifurcating axons pertained to neurons located in the dorsolateral cortex. Moreover, callosal neurons bifurcate more often than subcortically projecting cells. We then quantified bifurcations formed by dissociated green fluorescent cells plated onto cortical slices. Cells grown over dorsolateral cortex bifurcated more often than those grown over medial cortex, irrespective of their positional origin in the donor. Removal of intermediate targets from the slices prevented bifurcation. We concluded that transient bifurcation and elimination of the lateral branch is a strategy employed by developing callosal axons in search of their targets. As cell body position and intermediate targets determine axon behaviour, we suggest that bifurcations are regulated by cues expressed in the environment.}, Author = {Garcez, Patricia P and Henrique, Narjara P and Furtado, Danilo A and Bolz, J{\"u}rgen and Lent, Roberto and Uziel, Daniela}, Date-Added = {2017-05-23 00:57:18 +0000}, Date-Modified = {2017-05-23 00:57:18 +0000}, Doi = {10.1111/j.1460-9568.2007.05387.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Mesh = {Age Factors; Amino Acids; Animals; Animals, Newborn; Axons; Cells, Cultured; Coculture Techniques; Corpus Callosum; Embryo, Mammalian; Female; Functional Laterality; Green Fluorescent Proteins; Male; Mice; Neural Pathways; Neurons; Pregnancy}, Month = {Mar}, Number = {5}, Pages = {1384-94}, pmid = {17425565}, Pst = {ppublish}, Title = {Axons of callosal neurons bifurcate transiently at the white matter before consolidating an interhemispheric projection}, Volume = {25}, Year = {2007}, url = {papers/Garcez_EurJNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2007.05387.x}} @article{Huang:2012, Abstract = {BACKGROUND: Adolescent alcohol abuse remains a serious public health concern, with nearly a third of high school seniors reporting heavy drinking in the previous month. METHODS: Using the high ethanol-consuming C57BL/6J mouse strain, we examined the effects of ethanol (3.75 g/kg, IP, daily for 45 days) on body weight and brain region mass (cerebral cortex, cerebellum, corpus callosum) during peri-adolescence (postnatal day [P]25 to 70) or adulthood (P180 to 225) of both males and females. RESULTS: In control peri-adolescent animals, body weight gain was greater in males compared with females. In the peri-adolescent exposure group, ethanol significantly reduced body weight gain to a similar extent in both male and female mice (82 and 84% of controls, respectively). In adult animals, body weight gain was much less than that of the peri-adolescent mice, with ethanol having a small but significant effect in males but not females. Between the control peri-adolescent and adult cohorts (measurements taken at P70 and 225, respectively), there were no significant differences in the mass of the cerebral cortex or the cerebellum from either male or female mice, although the rostro-caudal length of the corpus callosum increased slightly but significantly (6.1%) between these time points. CONCLUSIONS: Ethanol treatment significantly reduced the mass of the cerebral cortex in peri-adolescent (-3.1%), but not adult, treated mice. By contrast, ethanol significantly reduced the length of the corpus callosum in adult (-5.4%), but not peri-adolescent, treated mice. Future studies at the histological level may yield additional details concerning ethanol and the peri-adolescent brain.}, Author = {Huang, Chiming and Titus, Jennifer A and Bell, Richard L and Kapros, Tamas and Chen, Jie and Huang, Rosa}, Date-Added = {2017-05-19 17:17:59 +0000}, Date-Modified = {2017-05-19 17:17:59 +0000}, Doi = {10.1111/j.1530-0277.2012.01759.x}, Journal = {Alcohol Clin Exp Res}, Journal-Full = {Alcoholism, clinical and experimental research}, Mesh = {Age Factors; Alcoholism; Animals; Body Weight; Brain; Corpus Callosum; Disease Models, Animal; Ethanol; Female; Male; Mice; Mice, Inbred C57BL; Organ Size}, Month = {Oct}, Number = {10}, Pages = {1728-37}, pmid = {22433022}, Pst = {ppublish}, Title = {A mouse model for adolescent alcohol abuse: stunted growth and effects in brain}, Volume = {36}, Year = {2012}, url = {papers/Huang_AlcoholClinExpRes2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1530-0277.2012.01759.x}} @article{Wit:2016, Abstract = {The molecular diversification of cell surface molecules has long been postulated to impart specific surface identities on neuronal cell types. The existence of unique cell surface identities would allow neurons to distinguish one another and connect with their appropriate target cells. Although progress has been made in identifying cell type-specific surface molecule repertoires and in characterizing their extracellular interactions, determining how this molecular diversity contributes to the precise wiring of neural circuitry has proven challenging. Here, we review the role of the cadherin, neurexin, immunoglobulin and leucine-rich repeat protein superfamilies in the specification of connectivity. The emerging evidence suggests that the concerted actions of these proteins may critically contribute to the assembly of neural circuits.}, Author = {de Wit, Joris and Ghosh, Anirvan}, Date-Added = {2017-05-19 00:57:07 +0000}, Date-Modified = {2017-05-19 00:57:07 +0000}, Doi = {10.1038/nrn.2015.3}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Brain; Cell Communication; Cell Membrane; Humans; Neurons; Proteins; Synapses}, Month = {Jan}, Number = {1}, Pages = {22-35}, pmid = {26656254}, Pst = {ppublish}, Title = {Specification of synaptic connectivity by cell surface interactions}, Volume = {17}, Year = {2016}, url = {papers/Wit_NatRevNeurosci2016.pdf}} @article{Inoue:1998, Abstract = {Multiple subtypes of the cadherin homophilic cell-cell adhesion molecule are expressed differentially in developing and mature brains, each being expressed in restricted neuronal groups. Cadherin-6 (cad6) is one of such cadherins. Recent studies of cad6 mRNA expression in the postnatal mouse forebrain showed that it occurs in neurons constituting a specific subset of thalamocortical connections. Here we analyzed the localization of cad6 mRNA as well as its protein in the entire central nervous system and also in cranial ganglia of mice at late embryonic to postnatal stages. Our results showed that cad6 is expressed by a limited population of neurons or their precursors, which are synaptically connected to one another, throughout the perinatal stages, and that this expression delineates restricted neuronal circuits from the central to peripheral nervous systems, which include subpathways of the auditory, somatosensory, solitary, vestibular, and olivocerebellar systems. cad6 proteins were detected in these cad6 mRNA-positive neurons on the surface of their cell bodies or dendrites as well as in the cytoplasm. Confocal microscopic analysis revealed that the cad6 protein distribution overlapped that of synaptotagmin in synapse forming areas, suggesting that homotypic cad6 interactions are involved in synaptic connections between neurons expressing this protein. These findings support the idea that cadherin-mediated cell-cell adhesions take part in specific interneuronal connections.}, Author = {Inoue, T and Tanaka, T and Suzuki, S C and Takeichi, M}, Date-Added = {2017-05-19 00:54:36 +0000}, Date-Modified = {2017-05-19 00:54:36 +0000}, Doi = {10.1002/(SICI)1097-0177(199804)211:4<338::AID-AJA5>3.0.CO;2-I}, Journal = {Dev Dyn}, Journal-Full = {Developmental dynamics : an official publication of the American Association of Anatomists}, Mesh = {Age Factors; Animals; Blotting, Northern; Blotting, Western; Brain; Cadherins; Immunohistochemistry; In Situ Hybridization; Interneurons; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Microtubule-Associated Proteins; Neurons; Synapses; Time Factors}, Month = {Apr}, Number = {4}, Pages = {338-51}, pmid = {9566953}, Pst = {ppublish}, Title = {Cadherin-6 in the developing mouse brain: expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry}, Volume = {211}, Year = {1998}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1097-0177(199804)211:4%3C338::AID-AJA5%3E3.0.CO;2-I}} @article{Nakagawa:1999, Abstract = {The differentiation of areas of the mammalian neocortex has been hypothesized to be controlled by intrinsic genetic programs and extrinsic influences such as those mediated by thalamocortical afferents (TCAs). To address the interplay between these intrinsic and extrinsic mechanisms in the process of arealization, we have analyzed the requirement of TCAs in establishing or maintaining graded or areal patterns of gene expression in the developing mouse neocortex. We describe the differential expression of Lhx2, SCIP, and Emx1, representatives of three different classes of transcription factors, and the type II classical cadherins Cad6, Cad8, and Cad11, which are expressed in graded or areal patterns, as well as layer-specific patterns, in the cortical plate. The differential expression of Lhx2, SCIP, Emx1, and Cad8 in the cortical plate is not evident until after TCAs reach the cortex, whereas Cad6 and Cad11 show subtle graded patterns of expression before the arrival of TCAs, which later become stronger. We find that these genes exhibit normal-appearing graded or areal expression patterns in Mash-1 mutant mice that fail to develop a TCA projection. These findings show that TCAs are not required for the establishment or maintenance of the graded and areal expression patterns of these genes and strongly suggest that their regulation is intrinsic to the developing neocortex.}, Author = {Nakagawa, Y and Johnson, J E and O'Leary, D D}, Date-Added = {2017-05-19 00:53:31 +0000}, Date-Modified = {2017-05-19 00:53:31 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors; Cadherins; Cerebral Cortex; DNA-Binding Proteins; Embryo, Mammalian; Gene Expression; Genes, Regulator; Homeodomain Proteins; LIM-Homeodomain Proteins; Mice; Mice, Inbred ICR; Mice, Neurologic Mutants; Neocortex; Neural Pathways; Octamer Transcription Factor-6; Thalamus; Time Factors; Transcription Factors}, Month = {Dec}, Number = {24}, Pages = {10877-85}, pmid = {10594069}, Pst = {ppublish}, Title = {Graded and areal expression patterns of regulatory genes and cadherins in embryonic neocortex independent of thalamocortical input}, Volume = {19}, Year = {1999}, url = {papers/Nakagawa_JNeurosci1999.pdf}} @article{Suzuki:1997, Abstract = {A number of type-II classic cadherin cell-cell adhesion molecules are expressed in the brain. To investigate their roles in brain morphogenesis, we selected three type-II cadherins, cadherin-6 (cad6), -8 (cad8) and -11 (cad11), and mapped their expressions in the forebrain and other restricted regions of postnatal mouse brains. In the cerebral cortex, each cortical area previously defined was delineated by a specific combinatorial expression of these cadherins. The thalamus and other subcortical regions of the forebrain were also subdivided by differential expression of the three cadherins; e.g., the medial geniculate body expressed only cad6; the ventral posterior thalamic nucleus, cad6/cad11; and the anteroventral thalamic nucleus, cad6/cad8. Likewise, in the olivocerebellar system, each subdivision of the inferior olive expressed a unique set of the three cadherins, and the cerebellar cortex had parasagittal stripes of cad8/cad11 expressions. Close analysis of these cadherin expression patterns revealed that they are correlated with neuronal connection patterns. Examples of these correlations include that cad6 delineates the auditory projection system, cad6/cad8/ cad11 are expressed by part of the Papez circuit, and cad6/cad8 are expressed by subdivisions of the olivo-nuclear circuit. Together with the recent finding that the cadherin adhesion system is localized in synaptic junctions, our findings support the notion that cadherin-mediated cell-cell adhesion plays a role in selective interneuronal connections during neural network formation.}, Author = {Suzuki, S C and Inoue, T and Kimura, Y and Tanaka, T and Takeichi, M}, Date-Added = {2017-05-19 00:22:35 +0000}, Date-Modified = {2017-05-19 00:22:35 +0000}, Doi = {10.1006/mcne.1997.0626}, Journal = {Mol Cell Neurosci}, Journal-Full = {Molecular and cellular neurosciences}, Mesh = {Animals; Animals, Newborn; Brain; Cadherins; Cell Differentiation; Cerebellum; Cerebral Cortex; Mice; Mice, Inbred ICR; Neurons; Olivary Nucleus; Thalamus}, Number = {5-6}, Pages = {433-47}, pmid = {9361280}, Pst = {ppublish}, Title = {Neuronal circuits are subdivided by differential expression of type-II classic cadherins in postnatal mouse brains}, Volume = {9}, Year = {1997}, url = {papers/Suzuki_MolCellNeurosci1997.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/mcne.1997.0626}} @article{Kim:2011a, Abstract = {Cadherins play a key role in the dynamics of cell-cell contact formation and remodeling of junctions and tissues. Cadherin-cadherin interactions are gated by extracellular Ca(2+), which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions (τ = 1.17 $\pm$ 0.06 s(-1)) upon chelation of extracellular Ca(2+). A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions (τ = 0.86 $\pm$ 0.02 s(-1)), suggesting two types of native cadherin interactions--one that is rapidly modulated by changes in extracellular Ca(2+) and another with relatively stable adhesive activity that is Ca(2+) independent. The Ca(2+)-sensitive dynamics of cadherin interactions were transmitted to the cell interior where β-catenin translocated to N-cadherin at the junction in both cells. These data indicate that cadherins can rapidly convey dynamic information about the extracellular environment to both cells that comprise a junction.}, Author = {Kim, Sally A and Tai, Chin-Yin and Mok, Lee-Peng and Mosser, Eric A and Schuman, Erin M}, Date-Added = {2017-05-19 00:12:46 +0000}, Date-Modified = {2017-05-19 00:12:46 +0000}, Doi = {10.1073/pnas.1019003108}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; COS Cells; Cadherins; Calcium; Cercopithecus aethiops; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; HEK293 Cells; Humans; Intercellular Junctions; Kinetics; L Cells (Cell Line); Mice; Microscopy, Confocal; Protein Binding; Recombinant Fusion Proteins; Transfection; beta Catenin}, Month = {Jun}, Number = {24}, Pages = {9857-62}, Pmc = {PMC3116393}, pmid = {21613566}, Pst = {ppublish}, Title = {Calcium-dependent dynamics of cadherin interactions at cell-cell junctions}, Volume = {108}, Year = {2011}, url = {papers/Kim_ProcNatlAcadSciUSA2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1019003108}} @article{Tepass:2000, Abstract = {Cadherins not only maintain the structural integrity of cells and tissues but also control a wide array of cellular behaviours. They are instrumental for cell and tissue polarization, and they regulate cell movements such as cell sorting, cell migration and cell rearrangements. Cadherins may also contribute to neurite outgrowth and pathfinding, and to synaptic specificity and modulation in the central nervous system.}, Author = {Tepass, U and Truong, K and Godt, D and Ikura, M and Peifer, M}, Date-Added = {2017-05-19 00:02:41 +0000}, Date-Modified = {2017-05-19 00:02:41 +0000}, Doi = {10.1038/35040042}, Journal = {Nat Rev Mol Cell Biol}, Journal-Full = {Nature reviews. Molecular cell biology}, Mesh = {Amino Acid Sequence; Animals; Cadherins; Cell Adhesion; Central Nervous System; Embryonic and Fetal Development; Humans; Molecular Sequence Data; Morphogenesis; Nervous System; Protein Structure, Secondary; Sequence Alignment; Sequence Homology, Amino Acid; Synapses}, Month = {Nov}, Number = {2}, Pages = {91-100}, pmid = {11253370}, Pst = {ppublish}, Title = {Cadherins in embryonic and neural morphogenesis}, Volume = {1}, Year = {2000}, url = {papers/Tepass_NatRevMolCellBiol2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35040042}} @article{Gumbiner:2005, Abstract = {Cadherin cell-adhesion proteins mediate many facets of tissue morphogenesis. The dynamic regulation of cadherins in response to various extracellular signals controls cell sorting, cell rearrangements and cell movements. Cadherins are regulated at the cell surface by an inside-out signalling mechanism that is analogous to the integrins in platelets and leukocytes. Signal-transduction pathways impinge on the catenins (cytoplasmic cadherin-associated proteins), which transduce changes across the membrane to alter the state of the cadherin adhesive bond.}, Author = {Gumbiner, Barry M}, Date-Added = {2017-05-18 23:34:43 +0000}, Date-Modified = {2017-05-18 23:34:43 +0000}, Doi = {10.1038/nrm1699}, Journal = {Nat Rev Mol Cell Biol}, Journal-Full = {Nature reviews. Molecular cell biology}, Mesh = {Animals; Cadherins; Cell Adhesion; Cell Movement; Cytoskeletal Proteins; Intercellular Junctions; Morphogenesis; Signal Transduction}, Month = {Aug}, Number = {8}, Pages = {622-34}, pmid = {16025097}, Pst = {ppublish}, Title = {Regulation of cadherin-mediated adhesion in morphogenesis}, Volume = {6}, Year = {2005}, url = {papers/Gumbiner_NatRevMolCellBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrm1699}} @article{Gumbiner:1996, Abstract = {A variety of cell adhesion mechanisms underlie the way that cells are organized in tissues. Stable cell interactions are needed to maintain the structural integrity of tissues, and dynamic changes in cell adhesion participate in the morphogenesis of developing tissues. Stable interactions actually require active adhesion mechanisms that are very similar to those involved in tissue dynamics. Adhesion mechanisms are highly regulated during tissue morphogenesis and are intimately related to the processes of cell motility and cell migration. In particular, the cadherins and the integrins have been implicated in the control of cell movement. Cadherin mediated cell compaction and cellular rearrangements may be analogous to integrin-mediated cell spreading and motility on the ECM. Regulation of cell adhesion can occur at several levels, including affinity modulation, clustering, and coordinated interactions with the actin cytoskeleton. Structural studies have begun to provide a picture of how the binding properties of adhesion receptors themselves might be regulated. However, regulation of tissue morphogenesis requires complex interactions between the adhesion receptors, the cytoskeleton, and networks of signaling pathways. Signals generated locally by the adhesion receptors themselves are involved in the regulation of cell adhesion. These regulatory pathways are also influenced by extrinsic signals arising from the classic growth factor receptors. Furthermore, signals generated locally be adhesion junctions can interact with classic signal transduction pathways to help control cell growth and differentiation. This coupling between physical adhesion and developmental signaling provides a mechanism to tightly integrate physical aspects of tissue morphogenesis with cell growth and differentiation, a coordination that is essential to achieve the intricate patterns of cells in tissues.}, Author = {Gumbiner, B M}, Date-Added = {2017-05-18 23:34:08 +0000}, Date-Modified = {2017-05-18 23:34:08 +0000}, Journal = {Cell}, Journal-Full = {Cell}, Mesh = {Animals; Basement Membrane; Cadherins; Cell Adhesion; Cell Movement; Desmosomes; Extracellular Matrix; Humans; Integrins; Intercellular Junctions; Models, Biological; Morphogenesis; Signal Transduction}, Month = {Feb}, Number = {3}, Pages = {345-57}, pmid = {8608588}, Pst = {ppublish}, Title = {Cell adhesion: the molecular basis of tissue architecture and morphogenesis}, Volume = {84}, Year = {1996}, url = {papers/Gumbiner_Cell1996.pdf}} @article{Wang:2009a, Abstract = {Research in cellular mechanotransduction often focuses on how extracellular physical forces are converted into chemical signals at the cell surface. However, mechanical forces that are exerted on surface-adhesion receptors, such as integrins and cadherins, are also channelled along cytoskeletal filaments and concentrated at distant sites in the cytoplasm and nucleus. Here, we explore the molecular mechanisms by which forces might act at a distance to induce mechanochemical conversion in the nucleus and alter gene activities.}, Author = {Wang, Ning and Tytell, Jessica D and Ingber, Donald E}, Date-Added = {2017-05-18 23:31:51 +0000}, Date-Modified = {2017-05-18 23:31:51 +0000}, Doi = {10.1038/nrm2594}, Journal = {Nat Rev Mol Cell Biol}, Journal-Full = {Nature reviews. Molecular cell biology}, Mesh = {Animals; Cell Nucleus; Cytoplasm; Extracellular Matrix; Humans; Mechanotransduction, Cellular; Stress, Mechanical}, Month = {Jan}, Number = {1}, Pages = {75-82}, pmid = {19197334}, Pst = {ppublish}, Title = {Mechanotransduction at a distance: mechanically coupling the extracellular matrix with the nucleus}, Volume = {10}, Year = {2009}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrm2594}} @article{Takeichi:1988, Abstract = {Cadherins are a family of glycoproteins involved in the Ca2+-dependent cell-cell adhesion mechanism which is detected in most kinds of tissues. Inhibition of the cadherin activity with antibodies induces dissociation of cell layers, indicating a fundamental importance of these molecules in maintaining the multicellular structure. Cadherins are divided into subclasses, including E-, N- and P-cadherins. While all subclasses are similar in molecular weight, Ca2+- and protease-sensitivity, each subclass is characterized by a unique tissue distribution pattern and immunological specificity. Analysis of amino acid sequences deduced from cDNA encoding these molecules showed that they are integral membrane proteins of 723-748 amino acids long and share common sequences; similarity in the sequences between subclasses is in a range of 50-60% when compared within a single animal species. L cells, with very little endogenous cadherin activity, transfected with the cadherin cDNA acquired high cadherin-mediated aggregating activity. Their colony morphology was altered by the ectopic expression of cadherins from the dispersed type to the compact type, providing direct evidence for a key role of cadherins in cell-cell adhesion. It has been suggested that cadherins bind cells by their homophilic interactions at the extracellular domain and are associated with actin bundles at the cytoplasmic domain. It appears that each cadherin subclass has binding specificity and this molecular family is involved in selective cell-cell adhesion. In development, the expression of each cadherin subclass is spatiotemporally regulated and associated with a variety of morphogenetic events; e.g. the termination or initiation of expression of a cadherin subclass in a given cell collective is correlated with its segregation from or connection with other cell collectives. Antibodies to cadherins were shown to perturb the morphogenesis of some embryonic organs in vitro. These observations suggest that cadherins play a crucial role in construction of tissues and the whole animal body.}, Author = {Takeichi, M}, Date-Added = {2017-05-18 23:30:43 +0000}, Date-Modified = {2017-05-18 23:30:43 +0000}, Journal = {Development}, Journal-Full = {Development (Cambridge, England)}, Mesh = {Animals; Antigens, Surface; Calcium-Binding Proteins; Cell Adhesion; Cell Adhesion Molecules; Membrane Glycoproteins; Morphogenesis}, Month = {Apr}, Number = {4}, Pages = {639-55}, pmid = {3048970}, Pst = {ppublish}, Title = {The cadherins: cell-cell adhesion molecules controlling animal morphogenesis}, Volume = {102}, Year = {1988}} @article{Frisch:2001, Abstract = {Anoikis is defined as apoptosis that is induced by inadequate or inappropriate cell-matrix interactions. It is involved in a wide diversity of tissue-homeostatic, developmental and oncogenic processes. The central problem of anoikis is to understand how integrin-mediated cell adhesion signals control the apoptotic machinery. In particular, the initiation of the caspase cascade in anoikis remains to be explained.}, Author = {Frisch, S M and Screaton, R A}, Date-Added = {2017-05-18 23:27:58 +0000}, Date-Modified = {2017-05-18 23:27:58 +0000}, Journal = {Curr Opin Cell Biol}, Journal-Full = {Current opinion in cell biology}, Mesh = {Adaptor Proteins, Signal Transducing; Anoikis; Carrier Proteins; Cytoskeleton; Fas-Associated Death Domain Protein; Growth Substances; Humans; Integrins; MAP Kinase Signaling System; Models, Biological; Neoplasms; Phosphatidylinositol 3-Kinases; Protein-Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Signal Transduction}, Month = {Oct}, Number = {5}, Pages = {555-62}, pmid = {11544023}, Pst = {ppublish}, Title = {Anoikis mechanisms}, Volume = {13}, Year = {2001}} @article{Nelson:2002, Abstract = {Contact inhibition of cell proliferation evokes a unique cellular program of growth arrest compared with stress, age, or other physical constraints. The last decade of research on genes activated by cell-cell contact has uncovered features of transmembrane signaling, cytoskeletal reorganization, and transcriptional control that initiate and maintain a quiescent phenotype. This review will focus on mechanisms controlling contact inhibition of cell proliferation, highlighting specific gene expression responses that are activated by cell-cell contact. Although a temporal framework for imposition of these mechanisms has not yet been well described, contact inhibition of cell proliferation clearly requires their coordinated function. Novel targets for intervention in proliferative disorders are emerging from these studies.}, Author = {Nelson, Peter J and Daniel, Thomas O}, Date-Added = {2017-05-18 23:25:29 +0000}, Date-Modified = {2017-05-18 23:25:29 +0000}, Doi = {10.1046/j.1523-1755.2002.0610s1099.x}, Journal = {Kidney Int}, Journal-Full = {Kidney international}, Mesh = {Cell Communication; Cell Proliferation; Gene Expression; Molecular Biology; Receptors, Cell Surface}, Month = {Jan}, Number = {1 Suppl}, Pages = {S99-105}, pmid = {11841621}, Pst = {ppublish}, Title = {Emerging targets: molecular mechanisms of cell contact-mediated growth control}, Volume = {61}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1046/j.1523-1755.2002.0610s1099.x}} @article{Radhakrishnan:2014, Abstract = {Cannabis is the most commonly used illicit drug worldwide, with ~5 million daily users worldwide. Emerging evidence supports a number of associations between cannabis and psychosis/psychotic disorders, including schizophrenia. These associations-based on case-studies, surveys, epidemiological studies, and experimental studies indicate that cannabinoids can produce acute, transient effects; acute, persistent effects; and delayed, persistent effects that recapitulate the psychopathology and psychophysiology seen in schizophrenia. Acute exposure to both cannabis and synthetic cannabinoids (Spice/K2) can produce a full range of transient psychotomimetic symptoms, cognitive deficits, and psychophysiological abnormalities that bear a striking resemblance to symptoms of schizophrenia. In individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Several factors appear to moderate these associations, including family history, genetic factors, history of childhood abuse, and the age at onset of cannabis use. Exposure to cannabinoids in adolescence confers a higher risk for psychosis outcomes in later life and the risk is dose-related. Individuals with polymorphisms of COMT and AKT1 genes may be at increased risk for psychotic disorders in association with cannabinoids, as are individuals with a family history of psychotic disorders or a history of childhood trauma. The relationship between cannabis and schizophrenia fulfills many but not all of the standard criteria for causality, including temporality, biological gradient, biological plausibility, experimental evidence, consistency, and coherence. At the present time, the evidence indicates that cannabis may be a component cause in the emergence of psychosis, and this warrants serious consideration from the point of view of public health policy.}, Author = {Radhakrishnan, Rajiv and Wilkinson, Samuel T and D'Souza, Deepak Cyril}, Date-Added = {2017-05-18 21:05:51 +0000}, Date-Modified = {2017-05-18 21:05:51 +0000}, Doi = {10.3389/fpsyt.2014.00054}, Journal = {Front Psychiatry}, Journal-Full = {Frontiers in psychiatry}, Keywords = {cannabis; psychophysiology; psychosis; schizophrenia; schizotypy; spice; synthetic cannabinoids}, Pages = {54}, Pmc = {PMC4033190}, pmid = {24904437}, Pst = {epublish}, Title = {Gone to Pot - A Review of the Association between Cannabis and Psychosis}, Volume = {5}, Year = {2014}, url = {papers/Radhakrishnan_FrontPsychiatry2014.pdf}} @article{Zaidel-Bar:2007, Abstract = {A detailed depiction of the 'integrin adhesome', consisting of a complex network of 156 components linked together and modified by 690 interactions is presented. Different views of the network reveal several functional 'subnets' that are involved in switching on or off many of the molecular interactions within the network, consequently affecting cell adhesion, migration and cytoskeletal organization. Examination of the adhesome network motifs reveals a relatively small number of key motifs, dominated by three-component complexes in which a scaffolding molecule recruits both a signalling molecule and its downstream target. We discuss the role of the different network modules in regulating the structural and signalling functions of cell-matrix adhesions.}, Author = {Zaidel-Bar, Ronen and Itzkovitz, Shalev and Ma'ayan, Avi and Iyengar, Ravi and Geiger, Benjamin}, Date-Added = {2017-05-18 20:33:31 +0000}, Date-Modified = {2017-05-18 20:33:31 +0000}, Doi = {10.1038/ncb0807-858}, Journal = {Nat Cell Biol}, Journal-Full = {Nature cell biology}, Mesh = {Animals; Cell Adhesion; Cell-Matrix Junctions; Cytoskeleton; Databases, Factual; Integrins; Signal Transduction}, Month = {Aug}, Number = {8}, Pages = {858-67}, Pmc = {PMC2735470}, pmid = {17671451}, Pst = {ppublish}, Title = {Functional atlas of the integrin adhesome}, Volume = {9}, Year = {2007}, url = {papers/Zaidel-Bar_NatCellBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb0807-858}} @article{Fletcher:2010, Abstract = {The ability of a eukaryotic cell to resist deformation, to transport intracellular cargo and to change shape during movement depends on the cytoskeleton, an interconnected network of filamentous polymers and regulatory proteins. Recent work has demonstrated that both internal and external physical forces can act through the cytoskeleton to affect local mechanical properties and cellular behaviour. Attention is now focused on how cytoskeletal networks generate, transmit and respond to mechanical signals over both short and long timescales. An important insight emerging from this work is that long-lived cytoskeletal structures may act as epigenetic determinants of cell shape, function and fate.}, Author = {Fletcher, Daniel A and Mullins, R Dyche}, Date-Added = {2017-05-17 17:43:45 +0000}, Date-Modified = {2017-05-17 17:43:45 +0000}, Doi = {10.1038/nature08908}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Biomechanical Phenomena; Cell Physiological Phenomena; Cell Shape; Cytoskeleton; Epigenesis, Genetic; Humans}, Month = {Jan}, Number = {7280}, Pages = {485-92}, Pmc = {PMC2851742}, pmid = {20110992}, Pst = {ppublish}, Title = {Cell mechanics and the cytoskeleton}, Volume = {463}, Year = {2010}, url = {papers/Fletcher_Nature2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08908}} @article{OBrien:1997, Abstract = {The effects of calcium (Ca) were assessed using video-enhanced differential interference contrast light microscopy on individual microtubules in vitro. Phosphocellulose-purified (PC) and microtubule associated protein (MAP)-containing preparations of porcine brain tubulin were assembled in a flow chamber onto sperm axoneme fragments and the pattern of growth and shortening of the microtubules was observed. Tubulin plus Ca was then added to the chamber and observation continued. Ca promoted the disassembly of microtubules by specifically promoting the catastrophe reaction in both PC- and MAP-containing microtubules, without an appreciable change in elongation rate. The effect on catastrophe frequency increased very rapidly above 0.5 mM free Ca, implying a possible cooperative effect. The rescue rate remained very high after Ca addition in MAP-containing microtubules, and the shortening rate was unchanged, while in phosphocellulose-purified microtubules, rescue appeared to be decreased by Ca addition and shortening rates increased 4 to 6-fold. These results illustrate that Ca can directly destabilize growing microtubule ends without changing the effective concentration of free tubulin, and that this effect can be seen even against the background of the profound differences in dynamics conferred by the microtubule-associated proteins. Considered within models of the GTP cap, the results imply that high Ca may act to increase the rate of GTP hydrolysis within the cap.}, Author = {O'Brien, E T and Salmon, E D and Erickson, H P}, Date-Added = {2017-05-17 17:42:40 +0000}, Date-Modified = {2017-05-17 17:42:40 +0000}, Doi = {10.1002/(SICI)1097-0169(1997)36:2<125::AID-CM3>3.0.CO;2-8}, Journal = {Cell Motil Cytoskeleton}, Journal-Full = {Cell motility and the cytoskeleton}, Mesh = {Animals; Biopolymers; Calcium; In Vitro Techniques; Microtubule-Associated Proteins; Microtubules; Sea Urchins; Swine; Tubulin}, Number = {2}, Pages = {125-35}, pmid = {9015201}, Pst = {ppublish}, Title = {How calcium causes microtubule depolymerization}, Volume = {36}, Year = {1997}, url = {papers/O'Brien_CellMotilCytoskeleton1997.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1097-0169(1997)36:2%3C125::AID-CM3%3E3.0.CO;2-8}} @article{Mattila:2008, Abstract = {Filopodia are thin, actin-rich plasma-membrane protrusions that function as antennae for cells to probe their environment. Consequently, filopodia have an important role in cell migration, neurite outgrowth and wound healing and serve as precursors for dendritic spines in neurons. The initiation and elongation of filopodia depend on the precisely regulated polymerization, convergence and crosslinking of actin filaments. The increased understanding of the functions of various actin-associated proteins during the initiation and elongation of filopodia has provided new information on the mechanisms of filopodia formation in distinct cell types.}, Author = {Mattila, Pieta K and Lappalainen, Pekka}, Date-Added = {2017-05-17 17:41:42 +0000}, Date-Modified = {2017-05-17 17:41:42 +0000}, Doi = {10.1038/nrm2406}, Journal = {Nat Rev Mol Cell Biol}, Journal-Full = {Nature reviews. Molecular cell biology}, Mesh = {Animals; Cell Movement; Humans; Pseudopodia}, Month = {Jun}, Number = {6}, Pages = {446-54}, pmid = {18464790}, Pst = {ppublish}, Title = {Filopodia: molecular architecture and cellular functions}, Volume = {9}, Year = {2008}, url = {papers/Mattila_NatRevMolCellBiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrm2406}} @article{Angelucci:1996, Abstract = {We report an improved immunohistochemical protocol for revealing anterograde axonal transport of the subunit B of cholera toxin (CTB) which stains axons and terminals in great detail, so that single axons can be followed over long distances and their arbors reconstructed in their entirety. Our modifications enhance the quality of staining mainly by increasing the penetration of the primary antibody in the tissue. The protocol can be modified to allow combination in alternate sections with tetramethylbenzidine (TMB) histochemical staining of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Using the protocol, we tested the performance of CTB as an anterograde tracer under two experimental paradigms which render other anterograde tracers less sensitive or unreliable: (1) labeling the entire retinofugal projection to the brain after injections into the vitreal chamber of the eye, and (2) labeling developing projections in the cortex and thalamus of early postnatal mammals. Qualitative comparisons were made with other tracers (Phaseolus vulgaris leucoagglutinin, dextran rhodamine, biotinylated dextran, free WGA, or WGA-HRP) that were used to label these same projections. From these observations it is clear that CTB, visualized with our protocol, provides more sensitive anterograde labeling of retinofugal projections as well as of axonal connections in the neonatal forebrain.}, Author = {Angelucci, A and Clasc{\'a}, F and Sur, M}, Date-Added = {2017-05-16 19:00:22 +0000}, Date-Modified = {2017-05-16 19:00:22 +0000}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Mesh = {Animals; Animals, Newborn; Axons; Benzidines; Biotin; Brain; Cholera Toxin; Chromogenic Compounds; Eye; Ferrets; Immunohistochemistry; Visual Pathways; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate}, Month = {Mar}, Number = {1}, Pages = {101-12}, pmid = {8815303}, Pst = {ppublish}, Title = {Anterograde axonal tracing with the subunit B of cholera toxin: a highly sensitive immunohistochemical protocol for revealing fine axonal morphology in adult and neonatal brains}, Volume = {65}, Year = {1996}, url = {papers/Angelucci_JNeurosciMethods1996.pdf}} @article{Bilkei-Gorzo:2017, Abstract = {The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging. The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here we show that a low dose of Δ(9)-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.}, Author = {Bilkei-Gorzo, Andras and Albayram, Onder and Draffehn, Astrid and Michel, Kerstin and Piyanova, Anastasia and Oppenheimer, Hannah and Dvir-Ginzberg, Mona and R{\'a}cz, Ildiko and Ulas, Thomas and Imbeault, Sophie and Bab, Itai and Schultze, Joachim L and Zimmer, Andreas}, Date-Added = {2017-05-16 00:12:44 +0000}, Date-Modified = {2017-05-16 00:12:44 +0000}, Doi = {10.1038/nm.4311}, Journal = {Nat Med}, Journal-Full = {Nature medicine}, Month = {May}, pmid = {28481360}, Pst = {aheadofprint}, Title = {A chronic low dose of Δ(9)-tetrahydrocannabinol (THC) restores cognitive function in old mice}, Year = {2017}, url = {papers/Bilkei-Gorzo_NatMed2017.pdf}} @article{Hollenbeck:2005, Abstract = {Organelle transport is vital for the development and maintenance of axons, in which the distances between sites of organelle biogenesis, function, and recycling or degradation can be vast. Movement of mitochondria in axons can serve as a general model for how all organelles move: mitochondria are easy to identify, they move along both microtubule and actin tracks, they pause and change direction, and their transport is modulated in response to physiological signals. However, they can be distinguished from other axonal organelles by the complexity of their movement and their unique functions in aerobic metabolism, calcium homeostasis and cell death. Mitochondria are thus of special interest in relating defects in axonal transport to neuropathies and degenerative diseases of the nervous system. Studies of mitochondrial transport in axons are beginning to illuminate fundamental aspects of the distribution mechanism. They use motors of one or more kinesin families, along with cytoplasmic dynein, to translocate along microtubules, and bidirectional movement may be coordinated through interaction between dynein and kinesin-1. Translocation along actin filaments is probably driven by myosin V, but the protein(s) that mediate docking with actin filaments remain unknown. Signaling through the PI 3-kinase pathway has been implicated in regulation of mitochondrial movement and docking in the axon, and additional mitochondrial linker and regulatory proteins, such as Milton and Miro, have recently been described.}, Author = {Hollenbeck, Peter J and Saxton, William M}, Date-Added = {2017-05-16 00:06:30 +0000}, Date-Modified = {2017-05-16 00:06:30 +0000}, Doi = {10.1242/jcs.02745}, Journal = {J Cell Sci}, Journal-Full = {Journal of cell science}, Mesh = {Animals; Axonal Transport; Dyneins; Humans; Kinesin; Mitochondria; Models, Biological; Myosins; Signal Transduction}, Month = {Dec}, Number = {Pt 23}, Pages = {5411-9}, Pmc = {PMC1533994}, pmid = {16306220}, Pst = {ppublish}, Title = {The axonal transport of mitochondria}, Volume = {118}, Year = {2005}, url = {papers/Hollenbeck_JCellSci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/jcs.02745}} @article{Saxton:2012, Abstract = {Vigorous transport of cytoplasmic components along axons over substantial distances is crucial for the maintenance of neuron structure and function. The transport of mitochondria, which serves to distribute mitochondrial functions in a dynamic and non-uniform fashion, has attracted special interest in recent years following the discovery of functional connections among microtubules, motor proteins and mitochondria, and their influences on neurodegenerative diseases. Although the motor proteins that drive mitochondrial movement are now well characterized, the mechanisms by which anterograde and retrograde movement are coordinated with one another and with stationary axonal mitochondria are not yet understood. In this Commentary, we review why mitochondria move and how they move, focusing particularly on recent studies of transport regulation, which implicate control of motor activity by specific cell-signaling pathways, regulation of motor access to transport tracks and static microtubule-mitochondrion linkers. A detailed mechanism for modulating anterograde mitochondrial transport has been identified that involves Miro, a mitochondrial Ca(2+)-binding GTPase, which with associated proteins, can bind and control kinesin-1. Elements of the Miro complex also have important roles in mitochondrial fission-fusion dynamics, highlighting questions about the interdependence of biogenesis, transport, dynamics, maintenance and degradation.}, Author = {Saxton, William M and Hollenbeck, Peter J}, Date-Added = {2017-05-15 23:57:16 +0000}, Date-Modified = {2017-05-15 23:57:16 +0000}, Doi = {10.1242/jcs.053850}, Journal = {J Cell Sci}, Journal-Full = {Journal of cell science}, Mesh = {Animals; Axonal Transport; Axons; Calcium; Drosophila melanogaster; Humans; Membrane Fusion; Microtubules; Mitochondria; Mitochondrial Proteins; Molecular Motor Proteins; Neurodegenerative Diseases; Protein Binding; Signal Transduction; rho GTP-Binding Proteins}, Month = {May}, Number = {Pt 9}, Pages = {2095-104}, Pmc = {PMC3656622}, pmid = {22619228}, Pst = {ppublish}, Title = {The axonal transport of mitochondria}, Volume = {125}, Year = {2012}, url = {papers/Saxton_JCellSci2012.pdf}} @article{Pilling:2006, Abstract = {To address questions about mechanisms of filament-based organelle transport, a system was developed to image and track mitochondria in an intact Drosophila nervous system. Mutant analyses suggest that the primary motors for mitochondrial movement in larval motor axons are kinesin-1 (anterograde) and cytoplasmic dynein (retrograde), and interestingly that kinesin-1 is critical for retrograde transport by dynein. During transport, there was little evidence that force production by the two opposing motors was competitive, suggesting a mechanism for alternate coordination. Tests of the possible coordination factor P150(Glued) suggested that it indeed influenced both motors on axonal mitochondria, but there was no evidence that its function was critical for the motor coordination mechanism. Observation of organelle-filled axonal swellings ("organelle jams" or "clogs") caused by kinesin and dynein mutations showed that mitochondria could move vigorously within and pass through them, indicating that they were not the simple steric transport blockades suggested previously. We speculate that axonal swellings may instead reflect sites of autophagocytosis of senescent mitochondria that are stranded in axons by retrograde transport failure; a protective process aimed at suppressing cell death signals and neurodegeneration.}, Author = {Pilling, Aaron D and Horiuchi, Dai and Lively, Curtis M and Saxton, William M}, Date-Added = {2017-05-15 23:38:27 +0000}, Date-Modified = {2017-05-15 23:38:27 +0000}, Doi = {10.1091/mbc.E05-06-0526}, Journal = {Mol Biol Cell}, Journal-Full = {Molecular biology of the cell}, Mesh = {Animals; Axons; Biological Transport; Drosophila; Drosophila Proteins; Dynactin Complex; Dyneins; Kinesin; Microtubule-Associated Proteins; Mitochondria; Motor Neurons; Mutation; Nervous System}, Month = {Apr}, Number = {4}, Pages = {2057-68}, Pmc = {PMC1415296}, pmid = {16467387}, Pst = {ppublish}, Title = {Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons}, Volume = {17}, Year = {2006}, url = {papers/Pilling_MolBiolCell2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1091/mbc.E05-06-0526}} @article{Macaskill:2009, Abstract = {Energy use, mainly to reverse ion movements in neurons, is a fundamental constraint on brain information processing. Trafficking of mitochondria to locations in neurons where there are large ion fluxes is essential for powering neural function. Mitochondrial trafficking is regulated by Ca2+ entry through ionotropic glutamate receptors, but the underlying mechanism is unknown. We show that the protein Miro1 links mitochondria to KIF5 motor proteins, allowing mitochondria to move along microtubules. This linkage is inhibited by micromolar levels of Ca2+ binding to Miro1. With the EF hand domains of Miro1 mutated to prevent Ca2+ binding, Miro1 could still facilitate mitochondrial motility, but mitochondrial stopping induced by glutamate or neuronal activity was blocked. Activating neuronal NMDA receptors with exogenous or synaptically released glutamate led to Miro1 positioning mitochondria at the postsynaptic side of synapses. Thus, Miro1 is a key determinant of how energy supply is matched to energy usage in neurons.}, Author = {Macaskill, Andrew F and Rinholm, Johanne E and Twelvetrees, Alison E and Arancibia-Carcamo, I Lorena and Muir, James and Fransson, Asa and Aspenstrom, Pontus and Attwell, David and Kittler, Josef T}, Date-Added = {2017-05-15 22:10:31 +0000}, Date-Modified = {2017-05-15 22:10:31 +0000}, Doi = {10.1016/j.neuron.2009.01.030}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Calcium Radioisotopes; Calcium Signaling; Cells, Cultured; Dendrites; Drosophila Proteins; Electrophysiology; Energy Metabolism; Glutathione Transferase; Immunoprecipitation; Kinesin; Mitochondria; Neurons; Rats; Receptors, Calcium-Sensing; Receptors, Glutamate; Synapses; rho GTP-Binding Proteins}, Month = {Feb}, Number = {4}, Pages = {541-55}, Pmc = {PMC2670979}, pmid = {19249275}, Pst = {ppublish}, Title = {Miro1 is a calcium sensor for glutamate receptor-dependent localization of mitochondria at synapses}, Volume = {61}, Year = {2009}, url = {papers/Macaskill_Neuron2009.pdf}, Bdsk-File-2 = {papers/Macaskill_Neuron2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.01.030}} @article{Hirokawa:2009, Abstract = {Intracellular transport is fundamental for cellular function, survival and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs. The mechanisms by which different kinesins recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of transport, have now been identified. Furthermore, recent molecular genetic experiments have uncovered important and unexpected roles for kinesins in the regulation of such physiological processes as higher brain function, tumour suppression and developmental patterning. These findings open exciting new areas of kinesin research.}, Author = {Hirokawa, Nobutaka and Noda, Yasuko and Tanaka, Yosuke and Niwa, Shinsuke}, Date-Added = {2017-05-15 22:06:46 +0000}, Date-Modified = {2017-05-15 22:06:46 +0000}, Doi = {10.1038/nrm2774}, Journal = {Nat Rev Mol Cell Biol}, Journal-Full = {Nature reviews. Molecular cell biology}, Mesh = {Animals; Biological Transport; Dyneins; Humans; Kinesin; Models, Biological; Molecular Motor Proteins; Organelles; Phylogeny; Proteins; RNA, Messenger}, Month = {Oct}, Number = {10}, Pages = {682-96}, pmid = {19773780}, Pst = {ppublish}, Title = {Kinesin superfamily motor proteins and intracellular transport}, Volume = {10}, Year = {2009}, url = {papers/Hirokawa_NatRevMolCellBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrm2774}} @article{King:2012, Abstract = {Axonemal dyneins are AAA(+) enzymes that convert ATP hydrolysis to mechanical work. This leads to the sliding of doublet microtubules with respect to each other and ultimately the generation of ciliary/flagellar beating. However, in order for useful work to be generated, the action of individual dynein motors must be precisely controlled. In addition, cells modulate the motility of these organelles through a variety of second messenger systems and these signals too must be integrated by the dynein motors to yield an appropriate output. This review describes the current status of efforts to understand dynein control mechanisms and their connectivity focusing mainly on studies of the outer dynein arm from axonemes of the unicellular biflagellate green alga Chlamydomonas.}, Author = {King, Stephen M}, Date-Added = {2017-05-15 18:51:59 +0000}, Date-Modified = {2017-05-15 18:51:59 +0000}, Doi = {10.1016/j.jsb.2012.02.013}, Journal = {J Struct Biol}, Journal-Full = {Journal of structural biology}, Mesh = {Axonemal Dyneins; Chlamydomonas; Dyneins}, Month = {Aug}, Number = {2}, Pages = {222-8}, Pmc = {PMC3378790}, pmid = {22406539}, Pst = {ppublish}, Title = {Integrated control of axonemal dynein AAA(+) motors}, Volume = {179}, Year = {2012}, url = {papers/King_JStructBiol2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jsb.2012.02.013}} @article{Humphries:2011, Abstract = {The endo-lysosomal pathway is essential for intracellular transport and the degradation of extracellular cargo. The relationship between three populations of endo-lysosomal vesicles--Rab7-positive, LAMP1-positive, and both Rab7- and LAMP1-postive--was probed with fluorescence microscopy and single particle tracking. Of specific interest was determining if these vesicles were intermediate or terminal vesicles in the transport of extracellular cargo. We find that the major organelle in the endo-lysosomal pathway, both in terms of population and cargo transport, is positive for Rab7 and LAMP1. Dextran, a fluid phase cargo, shifts from localization within all three populations of vesicles at 30 minutes and 1 hour to primarily LAMP1- and Rab7/LAMP1-vesicles at longer times. This demonstrates that LAMP1- and Rab7/LAMP1-vesicles are terminal vesicles in the endo-lysosomal pathway. We tested two possible mechanisms for this distribution of cargo, delivery to mannose 6-phosphate receptor (M6PR)-negative vesicles and the fusion dynamics of individual vesicles. We find no correlation with M6PR but do find that Rab7-vesicles undergo significantly fewer fusion events than LAMP1- or Rab7/LAMP1-vesicles suggesting that the distribution of fluid phase cargo is driven by vesicle dynamics.}, Author = {Humphries, 4th, William H and Szymanski, Craig J and Payne, Christine K}, Date-Added = {2017-05-11 21:39:29 +0000}, Date-Modified = {2017-05-11 21:39:29 +0000}, Doi = {10.1371/journal.pone.0026626}, Journal = {PLoS One}, Journal-Full = {PloS one}, Mesh = {Biological Transport; Cell Line; Dextrans; Endosomes; Humans; Lysosome-Associated Membrane Glycoproteins; Lysosomes; Microscopy, Confocal; rab GTP-Binding Proteins}, Number = {10}, Pages = {e26626}, Pmc = {PMC3200357}, pmid = {22039519}, Pst = {ppublish}, Title = {Endo-lysosomal vesicles positive for Rab7 and LAMP1 are terminal vesicles for the transport of dextran}, Volume = {6}, Year = {2011}, url = {papers/Humphries_PLoSOne2011.PDF}} @article{Maday:2014, Abstract = {Axonal transport is essential for neuronal function, and many neurodevelopmental and neurodegenerative diseases result from mutations in the axonal transport machinery. Anterograde transport supplies distal axons with newly synthesized proteins and lipids, including synaptic components required to maintain presynaptic activity. Retrograde transport is required to maintain homeostasis by removing aging proteins and organelles from the distal axon for degradation and recycling of components. Retrograde axonal transport also plays a major role in neurotrophic and injury response signaling. This review provides an overview of axonal transport pathways and discusses their role in neuronal function.}, Author = {Maday, Sandra and Twelvetrees, Alison E and Moughamian, Armen J and Holzbaur, Erika L F}, Date-Added = {2017-05-11 20:56:20 +0000}, Date-Modified = {2017-05-11 20:56:20 +0000}, Doi = {10.1016/j.neuron.2014.10.019}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Axonal Transport; Axons; Humans; Neurodegenerative Diseases; Neurons; Organelles; Signal Transduction}, Month = {Oct}, Number = {2}, Pages = {292-309}, Pmc = {PMC4269290}, pmid = {25374356}, Pst = {ppublish}, Title = {Axonal transport: cargo-specific mechanisms of motility and regulation}, Volume = {84}, Year = {2014}, url = {papers/Maday_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.10.019}} @article{Pan:2008, Abstract = {LIM-homeodomain (HD) and POU-HD transcription factors play crucial roles in neurogenesis. However, it remains largely unknown how they cooperate in this process and what downstream target genes they regulate. Here, we show that ISL1, a LIM-HD protein, is co-expressed with BRN3B, a POU-HD factor, in nascent post-mitotic retinal ganglion cells (RGCs). Similar to the Brn3b-null retinas, retina-specific deletion of Isl1 results in the apoptosis of a majority of RGCs and in RGC axon guidance defects. The Isl1 and Brn3b double null mice display more severe retinal abnormalities with a near complete loss of RGCs, indicating the synergistic functions of these two factors. Furthermore, we show that both Isl1 and Brn3b function downstream of Math5 to regulate the expression of a common set of RGC-specific genes. Whole-retina chromatin immunoprecipitation and in vitro transactivation assays reveal that ISL1 and BRN3B concurrently bind to and synergistically regulate the expression of a common set of RGC-specific genes. Thus, our results uncover a novel regulatory mechanism of BRN3B and ISL1 in RGC differentiation.}, Author = {Pan, Ling and Deng, Min and Xie, Xiaoling and Gan, Lin}, Date-Added = {2017-05-11 14:39:18 +0000}, Date-Modified = {2017-05-11 14:39:18 +0000}, Doi = {10.1242/dev.010751}, Journal = {Development}, Journal-Full = {Development (Cambridge, England)}, Mesh = {Animals; Cell Differentiation; Chromatin Immunoprecipitation; Gene Expression Regulation, Developmental; Homeodomain Proteins; Immunohistochemistry; In Situ Hybridization; LIM-Homeodomain Proteins; Mice; Mice, Knockout; Mitosis; Promoter Regions, Genetic; Protein Binding; Retina; Retinal Ganglion Cells; Transcription Factor Brn-3B; Transcription Factors}, Month = {Jun}, Number = {11}, Pages = {1981-90}, Pmc = {PMC2758274}, pmid = {18434421}, Pst = {ppublish}, Title = {ISL1 and BRN3B co-regulate the differentiation of murine retinal ganglion cells}, Volume = {135}, Year = {2008}, url = {papers/Pan_Development2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.010751}} @article{Yushkevich:2006, Abstract = {Active contour segmentation and its robust implementation using level set methods are well-established theoretical approaches that have been studied thoroughly in the image analysis literature. Despite the existence of these powerful segmentation methods, the needs of clinical research continue to be fulfilled, to a large extent, using slice-by-slice manual tracing. To bridge the gap between methodological advances and clinical routine, we developed an open source application called ITK-SNAP, which is intended to make level set segmentation easily accessible to a wide range of users, including those with little or no mathematical expertise. This paper describes the methods and software engineering philosophy behind this new tool and provides the results of validation experiments performed in the context of an ongoing child autism neuroimaging study. The validation establishes SNAP intrarater and interrater reliability and overlap error statistics for the caudate nucleus and finds that SNAP is a highly reliable and efficient alternative to manual tracing. Analogous results for lateral ventricle segmentation are provided.}, Author = {Yushkevich, Paul A and Piven, Joseph and Hazlett, Heather Cody and Smith, Rachel Gimpel and Ho, Sean and Gee, James C and Gerig, Guido}, Date-Added = {2017-05-10 18:30:24 +0000}, Date-Modified = {2017-05-10 18:30:24 +0000}, Doi = {10.1016/j.neuroimage.2006.01.015}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Mesh = {Brain; Caudate Nucleus; Dominance, Cerebral; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Mathematical Computing; Software; Software Validation; User-Computer Interface}, Month = {Jul}, Number = {3}, Pages = {1116-28}, pmid = {16545965}, Pst = {ppublish}, Title = {User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability}, Volume = {31}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2006.01.015}} @article{Rashid:2005, Abstract = {During development of the retinocollicular projection in mouse, retinal axons initially overshoot their future termination zones (TZs) in the superior colliculus (SC). The formation of TZs is initiated by interstitial branching at topographically appropriate positions. Ephrin-As are expressed in a decreasing posterior-to-anterior gradient in the SC, and they suppress branching posterior to future TZs. Here we investigate the role of an EphA7 gradient in the SC, which has the reverse orientation to the ephrin-A gradient. We find that in EphA7 mutant mice the retinocollicular map is disrupted, with nasal and temporal axons forming additional or extended TZs, respectively. In vitro, retinal axons are repelled from growing on EphA7-containing stripes. Our data support the idea that EphA7 is involved in suppressing branching anterior to future TZs. These findings suggest that opposing ephrin-A and EphA gradients are required for the proper development of the retinocollicular projection.}, Author = {Rashid, Tahira and Upton, A Louise and Blentic, Aida and Ciossek, Thomas and Kn{\"o}ll, Bernd and Thompson, Ian D and Drescher, Uwe}, Date-Added = {2017-05-09 18:36:46 +0000}, Date-Modified = {2017-05-09 18:36:46 +0000}, Doi = {10.1016/j.neuron.2005.05.030}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Axons; Brain Mapping; Ephrins; Histocytochemistry; In Situ Hybridization; Mice; Mice, Knockout; RNA; Receptor, EphA7; Retina; Superior Colliculi; Vision, Ocular; Visual Pathways}, Month = {Jul}, Number = {1}, Pages = {57-69}, pmid = {15996548}, Pst = {ppublish}, Title = {Opposing gradients of ephrin-As and EphA7 in the superior colliculus are essential for topographic mapping in the mammalian visual system}, Volume = {47}, Year = {2005}, url = {papers/Rashid_Neuron2005.pdf}} @article{Drescher:1995, Abstract = {The results of previous in vitro experiments indicate that a glycosylphosphatidylinositol (GPI)-anchored protein may play an important role in the guidance of temporal retinal axons during the formation of the topographically ordered retinotectal projection. We have purified and cloned a GPI-anchored, 25 kDa glycoprotein that is a good candidate for a molecule involved in this process. During the time of innervation by retinal ganglion cells, this protein is gradedly expressed in the posterior part of the developing tectum. In two different in vitro assay systems, the recombinant protein induces growth cone collapse and repulsion of retinal ganglion cell axons. These phenomena are observed for axons of temporal as well as nasal origin, indicating that an additional activity may be necessary to confer the nasotemporal specificity observed in previous assays. We named the protein RAGS (for repulsive axon guidance signal). The sequence of RAGS shows significant homology to recently identified ligands for receptor tyrosine kinases of the Eph subfamily.}, Author = {Drescher, U and Kremoser, C and Handwerker, C and L{\"o}schinger, J and Noda, M and Bonhoeffer, F}, Date-Added = {2017-05-06 00:25:56 +0000}, Date-Modified = {2017-05-06 00:25:56 +0000}, Journal = {Cell}, Journal-Full = {Cell}, Mesh = {Amino Acid Sequence; Animals; Axons; Base Sequence; Cell Communication; Cell Division; Cells, Cultured; Chickens; Cloning, Molecular; DNA, Complementary; Ephrin-A2; Glycoproteins; Humans; Molecular Sequence Data; Proteins; Retinal Ganglion Cells; Sequence Alignment; Superior Colliculi}, Month = {Aug}, Number = {3}, Pages = {359-70}, pmid = {7634326}, Pst = {ppublish}, Title = {In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases}, Volume = {82}, Year = {1995}, url = {papers/Drescher_Cell1995.pdf}} @article{Cheng:1995, Abstract = {Topographic maps with a defined spatial ordering of neuronal connections are a key feature of brain organization. Such maps are believed to develop in response to complementary position-specific labels in presynaptic and postsynaptic fields. However, the complementary labeling molecules are not known. In the well-studied visual map of retinal axons projecting to the tectum, the labels are hypothesized to be in gradients, without needing large numbers of cell-specific molecules. We recently cloned ELF-1 as a ligand for Eph family receptors. Here, RNA hybridization shows matching expression gradients for ELF-1 in the tectum and its receptor Mek4 in the retina. Binding activity detected with alkaline phosphatase fusions of ELF-1 and Mek4 also reveals gradients and provides direct evidence for molecular complementarity of gradients in reciprocal fields. ELF-1 and Mek4 may therefore play roles in retinotectal development and have properties predicted of topographic mapping labels.}, Author = {Cheng, H J and Nakamoto, M and Bergemann, A D and Flanagan, J G}, Date-Added = {2017-05-06 00:25:11 +0000}, Date-Modified = {2017-05-06 00:25:11 +0000}, Journal = {Cell}, Journal-Full = {Cell}, Mesh = {Amino Acid Sequence; Animals; Brain Mapping; Chickens; Ephrin-A2; Mice; Molecular Sequence Data; Proteins; Retinal Ganglion Cells; Sequence Homology, Amino Acid; Superior Colliculi}, Month = {Aug}, Number = {3}, Pages = {371-81}, pmid = {7634327}, Pst = {ppublish}, Title = {Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map}, Volume = {82}, Year = {1995}, url = {papers/Cheng_Cell1995.pdf}} @article{Flanagan:1998, Abstract = {The Eph receptors are the largest known family of receptor tyrosine kinases. Initially all of them were identified as orphan receptors without known ligands, and their specific functions were not well understood. During the past few years, a corresponding family of ligands has been identified, called the ephrins, and specific functions have now been identified in neural development. The ephrins and Eph receptors are implicated as positional labels that may guide the development of neural topographic maps. They have also been implicated in pathway selection by axons, the guidance of cell migration, and the establishment of regional pattern in the nervous system. The ligands are anchored to cell surfaces, and most of the functions so far identified can be interpreted as precise guidance of cell or axon movement. This large family of ligands and receptors may make a major contribution to the accurate spatial patterning of connections and cell position in the nervous system.}, Author = {Flanagan, J G and Vanderhaeghen, P}, Date-Added = {2017-05-06 00:24:27 +0000}, Date-Modified = {2017-05-06 00:24:27 +0000}, Doi = {10.1146/annurev.neuro.21.1.309}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Mesh = {Animals; Central Nervous System; Ephrin-A2; Ephrin-B1; Ephrin-B3; Membrane Proteins; Receptor Protein-Tyrosine Kinases; Transcription Factors}, Pages = {309-45}, pmid = {9530499}, Pst = {ppublish}, Title = {The ephrins and Eph receptors in neural development}, Volume = {21}, Year = {1998}, url = {papers/Flanagan_AnnuRevNeurosci1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.21.1.309}} @article{Mackarehtschian:1999, Abstract = {The development of axonal connections between thalamic nuclei and their cortical target areas occurs in a highly specific manner. To explore the mechanisms of thalamocortical axon pathfinding, we investigated the expression of several members of the ephrin and Eph gene families in the forebrain. The Eph ligand ephrin-A5 was expressed in three distinct gradients during the development of the telencephalon. The first gradient occurred in the cortical ventricular zone and established ephrin-A5 as one of the earliest markers distinguishing cells residing in the anterior versus posterior cortical neuroepithelium. The second gradient was apparent in the subplate and occurred in spatial opposition to a distinct gradient for the low-affinity NGF receptor p75. This finding reveals that different regions of the early subplate are molecularly heterogeneous. Third, we confirmed that ephrin-A5 is expressed in a bi-directional gradient in the cortical plate, with highest levels in the somatomotor cortex. Three putative receptors for ephrin-A5 -- EphA3, EphA4 and EphA5 -- showed distinct expression patterns in the developing thalamus. The graded distributions of ephrin-A5 in the developing subplate and cortex and the expression of its receptors in the thalamus are consistent with the notion that the Eph ligands and their receptors may function in the topographic mapping of thalamic axons to specific cortical areas.}, Author = {Mackarehtschian, K and Lau, C K and Caras, I and McConnell, S K}, Date-Added = {2017-05-06 00:05:56 +0000}, Date-Modified = {2017-05-06 00:05:56 +0000}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Benzoxazines; Brain Chemistry; Cerebral Cortex; Coloring Agents; DNA Probes; Ephrin-A4; Ephrin-A5; Female; Gene Expression Regulation, Developmental; In Situ Hybridization; Ligands; Membrane Proteins; Oxazines; Pregnancy; Prosencephalon; RNA, Messenger; Rats; Rats, Long-Evans; Receptor Protein-Tyrosine Kinases; Receptor, Nerve Growth Factor}, Month = {Sep}, Number = {6}, Pages = {601-10}, pmid = {10498278}, Pst = {ppublish}, Title = {Regional differences in the developing cerebral cortex revealed by ephrin-A5 expression}, Volume = {9}, Year = {1999}, url = {papers/Mackarehtschian_CerebCortex1999.pdf}} @article{Donoghue:1999a, Abstract = {The mature cerebral cortex is divided into morphologically distinct, functionally dedicated and stereotypically connected cortical areas. How might such functional domains arise during development? To investigate possible intrinsic programs within the embryonic cerebral cortex we examined patterns of gene expression early in corticogenesis. We performed these studies using the developing macaque monkey because of the size, complexity, areal make-up and the extended nature of its cortical development. Here, we present results for two types of molecules. (i) Transcription factors -- gene products that bind DNA and activate transcription, directing cellular fates through cascades of gene expression. We find that the transcription factors TBr-1, Lhx-2, Emx-1 and a novel POU domain-containing gene are differentially expressed within the forming primate forebrain, and are present in gradients across the neocortex. (ii) The EphA receptor tyrosine kinases -- gene products that mediate cellular recognition in many embryonic systems. Individual members of this family are expressed during primate corticogenesis in pronounced gradients and/or well-defined compartments with distinct boundaries. Together, these results suggest that at least two modes of grouping cells within the neocortex exist: the graded patterning of cells across its full anteroposterior extent and the parcellation of cells into defined domains. Moreover, emergence of molecular differences between regions of the cortical plate, prior to the arrival of afferent and formation of efferent connections, suggests that the initial cellular parcellation in the telencephalon is cell-autonomously regulated. This initial independence from peripheral influences supports the existence of an intrinsic protomap that may function both to differentially attract and respond to specific afferents, thus predicting the functional map of the mature cortex.}, Author = {Donoghue, M J and Rakic, P}, Date-Added = {2017-05-06 00:01:28 +0000}, Date-Modified = {2017-05-06 00:01:28 +0000}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Antisense Elements (Genetics); Brain Chemistry; Cloning, Molecular; DNA-Binding Proteins; Ephrin-A1; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Homeodomain Proteins; In Situ Hybridization; Macaca mulatta; Neocortex; Neurons; Pregnancy; Prosencephalon; Proteins; Receptor Protein-Tyrosine Kinases; Transcription Factors}, Month = {Sep}, Number = {6}, Pages = {586-600}, pmid = {10498277}, Pst = {ppublish}, Title = {Molecular gradients and compartments in the embryonic primate cerebral cortex}, Volume = {9}, Year = {1999}, url = {papers/Donoghue_CerebCortex1999.pdf}} @article{Vanderhaeghen:2000, Abstract = {The neocortical primary somatosensory area (S1) consists of a map of the body surface. The cortical area devoted to different regions, such as parts of the face or hands, reflects their functional importance. Here we investigated the role of genetically determined positional labels in neocortical mapping. Ephrin-A5 was expressed in a medial > lateral gradient across S1, whereas its receptor EphA4 was in a matching gradient across the thalamic ventrobasal (VB) complex, which provides S1 input. Ephrin-A5 had topographically specific effects on VB axon guidance in vitro. Ephrin-A5 gene disruption caused graded, topographically specific distortion in the S1 body map, with medial regions contracted and lateral regions expanded, changing relative areas up to 50% in developing and adult mice. These results provide evidence for within-area thalamocortical mapping labels and show that a genetic difference can cause a lasting change in relative scale of different regions within a topographic map.}, Author = {Vanderhaeghen, P and Lu, Q and Prakash, N and Fris{\'e}n, J and Walsh, C A and Frostig, R D and Flanagan, J G}, Date-Added = {2017-05-05 22:02:45 +0000}, Date-Modified = {2017-05-05 22:02:45 +0000}, Doi = {10.1038/73929}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Age Factors; Animals; Axons; Brain Mapping; Cell Line; Ephrin-A5; Gene Expression Regulation, Developmental; Membrane Proteins; Mice; Mice, Inbred C57BL; Mutagenesis; RNA, Messenger; Somatosensory Cortex; Thalamus; Transfection}, Month = {Apr}, Number = {4}, Pages = {358-65}, pmid = {10725925}, Pst = {ppublish}, Title = {A mapping label required for normal scale of body representation in the cortex}, Volume = {3}, Year = {2000}, url = {papers/Vanderhaeghen_NatNeurosci2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/73929}} @article{Lyckman:2001, Abstract = {Ascending sensory information reaches primary sensory cortical areas via thalamic relay neurons that are organized into modality-specific compartments or nuclei. Although the sensory relay nuclei of the thalamus show consistent modality-specific segregation of afferents, we now show in a wild-type mouse strain that the visual pathway can be surgically "rewired" so as to induce permanent retinal innervation of auditory thalamic cell groups. Applying the same rewiring paradigm to a transgenic mouse lacking the EphA receptor family ligands ephrin-A2 and ephrin-A5 results in more extensive rewiring than in the wild-type strain. We also show for the first time that ephrin-A2 and ephrin-A5 define a distinct border between visual and auditory thalamus. In the absence of this ephrin-A2/A5 border and after rewiring surgery, retinal afferents are better able to invade and innervate the deafferented auditory thalamus. These data suggest that signals that induce retinal axons to innervate the denervated auditory thalamus may compete with barriers, such as the ephrins, that serve to contain them within the normal target. The present findings thus show that the targeting of retinothalamic projections can be surgically manipulated in the mouse and that such plasticity can be controlled by proteins known to regulate topographic mapping.}, Author = {Lyckman, A W and Jhaveri, S and Feldheim, D A and Vanderhaeghen, P and Flanagan, J G and Sur, M}, Date-Added = {2017-05-05 22:01:38 +0000}, Date-Modified = {2017-05-05 22:01:38 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Animals, Newborn; Auditory Pathways; Axons; Ephrin-A2; Ephrin-A5; Fluorescent Dyes; Geniculate Bodies; Inferior Colliculi; Ligands; Membrane Proteins; Mice; Mice, Inbred Strains; Mice, Knockout; Neuronal Plasticity; Organ Specificity; RNA, Messenger; Retina; Thalamus; Transcription Factors; Visual Pathways}, Month = {Oct}, Number = {19}, Pages = {7684-90}, pmid = {11567058}, Pst = {ppublish}, Title = {Enhanced plasticity of retinothalamic projections in an ephrin-A2/A5 double mutant}, Volume = {21}, Year = {2001}, url = {papers/Lyckman_JNeurosci2001.pdf}} @article{Prakash:2000, Abstract = {The molecular mechanisms that coordinate the functional organization of the mammalian neocortex are largely unknown. We tested the involvement of a putative guidance label, ephrin-A5, in the functional organization of the somatosensory cortex by quantifying the functional representations of individual whiskers in vivo in adult ephrin-A5 knock-out mice, using intrinsic signal optical imaging. In wild-type mice ephrin-A5 is expressed in a gradient in the somatosensory cortex during development. In adult ephrin-A5 knock-out mice, we found a spatial gradient of change in the amount of cortical territory shared by individual whisker functional representations across the somatosensory cortex, as well as a gradient of change in the distance between the functional representations. Both gradients of change were in correspondence with the developmental expression gradient of ephrin-A5 in wild-type mice. These changes involved malformations of the cortical spacing of the thalamocortical components, without concurrent malformations of the intracortical components of individual whisker functional representations. Overall, these results suggest that a developmental guidance label, such as ephrin-A5, is involved in establishing certain spatial relationships of the functional organization of the adult neocortex, and they underscore the advantage of investigating gene manipulation using in vivo functional imaging.}, Author = {Prakash, N and Vanderhaeghen, P and Cohen-Cory, S and Fris{\'e}n, J and Flanagan, J G and Frostig, R D}, Date-Added = {2017-05-05 22:00:47 +0000}, Date-Modified = {2017-05-05 22:00:47 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Age Factors; Animals; Axons; Brain Mapping; Ephrin-A5; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Pathways; Optics and Photonics; Somatosensory Cortex; Thalamus; Vibrissae}, Month = {Aug}, Number = {15}, Pages = {5841-7}, pmid = {10908626}, Pst = {ppublish}, Title = {Malformation of the functional organization of somatosensory cortex in adult ephrin-A5 knock-out mice revealed by in vivo functional imaging}, Volume = {20}, Year = {2000}, url = {papers/Prakash_JNeurosci2000.pdf}} @article{Pollard:2006, Abstract = {The developmental and evolutionary mechanisms behind the emergence of human-specific brain features remain largely unknown. However, the recent ability to compare our genome to that of our closest relative, the chimpanzee, provides new avenues to link genetic and phenotypic changes in the evolution of the human brain. We devised a ranking of regions in the human genome that show significant evolutionary acceleration. Here we report that the most dramatic of these 'human accelerated regions', HAR1, is part of a novel RNA gene (HAR1F) that is expressed specifically in Cajal-Retzius neurons in the developing human neocortex from 7 to 19 gestational weeks, a crucial period for cortical neuron specification and migration. HAR1F is co-expressed with reelin, a product of Cajal-Retzius neurons that is of fundamental importance in specifying the six-layer structure of the human cortex. HAR1 and the other human accelerated regions provide new candidates in the search for uniquely human biology.}, Author = {Pollard, Katherine S and Salama, Sofie R and Lambert, Nelle and Lambot, Marie-Alexandra and Coppens, Sandra and Pedersen, Jakob S and Katzman, Sol and King, Bryan and Onodera, Courtney and Siepel, Adam and Kern, Andrew D and Dehay, Colette and Igel, Haller and Ares, Jr, Manuel and Vanderhaeghen, Pierre and Haussler, David}, Date-Added = {2017-05-05 21:57:52 +0000}, Date-Modified = {2017-05-05 21:59:46 +0000}, Doi = {10.1038/nature05113}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Neocortex; isocortex; Evolution}, Mesh = {Aging; Animals; Base Sequence; Cell Adhesion Molecules, Neuronal; Cerebral Cortex; Evolution, Molecular; Extracellular Matrix Proteins; Gene Expression Profiling; Gene Expression Regulation, Developmental; Humans; Macaca; Molecular Sequence Data; Mutation; Neocortex; Nerve Tissue Proteins; Nucleic Acid Conformation; Organ Specificity; RNA Stability; RNA, Untranslated; Serine Endopeptidases; Time Factors}, Month = {Sep}, Number = {7108}, Pages = {167-72}, pmid = {16915236}, Pst = {ppublish}, Title = {An RNA gene expressed during cortical development evolved rapidly in humans}, Volume = {443}, Year = {2006}, url = {papers/Pollard_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05113}} @article{Lee:2013a, Abstract = {The hypothesized negative relationship between growth rate and lifespan has proved very difficult to test robustly because of potentially confounding variables, particularly nutrient availability and final size. Here we provide, to our knowledge, the first rigorous experimental test of this hypothesis, and find dramatic changes in lifespan in the predicted direction in response to both upward and downward manipulations of growth rates. We used brief (less than 4% of median lifespan) exposure to relatively cold or warm temperatures early in life to deflect juvenile three-spined sticklebacks Gasterosteus aculeatus from their normal growth trajectories; this induced catch-up or slowed-down growth when ambient temperatures were restored, and all groups attained the same average adult size. Catch-up growth led to a reduction in median lifespan of 14.5 per cent, while slowed-down growth extended lifespan by 30.6 per cent. These lifespan effects were independent of eventual size attained or reproductive investment in adult life. Photoperiod manipulations showed that the effects of compensatory growth on lifespan were also influenced by time available for growth prior to breeding, being more extreme when less time was available. These results demonstrate the growth-lifespan trade-off. While growing more slowly can increase longevity, the optimal resolution of the growth-lifespan trade-off is influenced by time constraints in a seasonal environment.}, Author = {Lee, Who-Seung and Monaghan, Pat and Metcalfe, Neil B}, Date-Added = {2017-05-05 21:48:59 +0000}, Date-Modified = {2017-05-05 21:48:59 +0000}, Doi = {10.1098/rspb.2012.2370}, Journal = {Proc Biol Sci}, Journal-Full = {Proceedings. Biological sciences}, Mesh = {Animals; Environment; Female; Genetic Fitness; Longevity; Male; Photoperiod; Reproduction; Scotland; Seasons; Smegmamorpha; Temperature}, Month = {Feb}, Number = {1752}, Pages = {20122370}, Pmc = {PMC3574304}, pmid = {23235704}, Pst = {epublish}, Title = {Experimental demonstration of the growth rate--lifespan trade-off}, Volume = {280}, Year = {2013}, url = {papers/Lee_ProcBiolSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1098/rspb.2012.2370}} @article{Mizuno:2014, Abstract = {Thalamocortical (TC) connectivity is reorganized by thalamic inputs during postnatal development; however, the dynamic characteristics of TC reorganization and the underlying mechanisms remain unexplored. We addressed this question using dendritic refinement of layer 4 (L4) stellate neurons in mouse barrel cortex (barrel cells) as a model; dendritic refinement of L4 neurons is a critical component of TC reorganization through which postsynaptic L4 neurons acquire their dendritic orientation toward presynaptic TC axon termini. Simultaneous labeling of TC axons and individual barrel cell dendrites allowed in vivo time-lapse imaging of dendritic refinement in the neonatal cortex. The barrel cells reinforced the dendritic orientation toward TC axons by dynamically moving their branches. In N-methyl-D-aspartate receptor (NMDAR)-deficient barrel cells, this dendritic motility was enhanced, and the orientation bias was not reinforced. Our data suggest that L4 neurons have "fluctuating" dendrites during TC reorganization and that NMDARs cell autonomously regulate these dynamics to establish fine-tuned circuits.}, Author = {Mizuno, Hidenobu and Luo, Wenshu and Tarusawa, Etsuko and Saito, Yoshikazu M and Sato, Takuya and Yoshimura, Yumiko and Itohara, Shigeyoshi and Iwasato, Takuji}, Date-Added = {2017-05-05 21:35:01 +0000}, Date-Modified = {2017-05-05 21:35:01 +0000}, Doi = {10.1016/j.neuron.2014.02.026}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Animals, Newborn; Cerebral Cortex; Dendrites; Excitatory Amino Acid Agonists; Excitatory Postsynaptic Potentials; Female; Gene Expression Regulation, Developmental; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Biological; N-Methylaspartate; Nerve Tissue Proteins; Neural Pathways; Neurons; Receptors, N-Methyl-D-Aspartate; Thalamus; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid}, Month = {Apr}, Number = {2}, Pages = {365-79}, pmid = {24685175}, Pst = {ppublish}, Title = {NMDAR-regulated dynamics of layer 4 neuronal dendrites during thalamocortical reorganization in neonates}, Volume = {82}, Year = {2014}, url = {papers/Mizuno_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.02.026}} @article{Barbas:1997, Abstract = {Cortical areas are linked through pathways which originate and terminate in specific layers. The factors underlying which layers are involved in specific connections are not well understood. Here we tested whether cortical structure can predict the pattern as well as the relative distribution of projection neurons and axonal terminals in cortical layers, studied with retrograde and anterograde tracers. We used the prefrontal cortices in the rhesus monkey as a model system because their laminar organization varies systematically, ranging from areas that have only three identifiable layers, to those that have six layers. We rated each prefrontal area based on the number and definition of its cortical layers (level 1, lowest; level 5, highest). The structural model accurately predicted the laminar pattern of connections in approximately 80% of the cases. Thus, projection neurons from a higher-level cortex originated mostly in the upper layers and their axons terminated predominantly in the deep layers (4-6) of a lower-level cortex. Conversely, most projection neurons from a lower-level area originated in the deep layers and their axons terminated predominantly in the upper layers (1-3) of a higher-level area. In addition, the structural model accurately predicted that the proportion of projection neurons or axonal terminals in the upper to the deep layers would vary as a function of the number of levels between the connected cortices. The power of this structural model lies in its potential to predict patterns of connections in the human cortex, where invasive procedures are precluded.}, Author = {Barbas, H and Rempel-Clower, N}, Date = {1997 Oct-Nov}, Date-Added = {2017-05-05 20:59:22 +0000}, Date-Modified = {2017-05-05 20:59:22 +0000}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Axonal Transport; Axons; Brain Mapping; Cerebral Cortex; Humans; Macaca mulatta; Models, Anatomic; Neurons; Prefrontal Cortex; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate}, Number = {7}, Pages = {635-46}, pmid = {9373019}, Pst = {ppublish}, Title = {Cortical structure predicts the pattern of corticocortical connections}, Volume = {7}, Year = {1997}, url = {papers/Barbas_CerebCortex1997.pdf}} @article{Barrett:2015, Abstract = {Intuition suggests that perception follows sensation and therefore bodily feelings originate in the body. However, recent evidence goes against this logic: interoceptive experience may largely reflect limbic predictions about the expected state of the body that are constrained by ascending visceral sensations. In this Opinion article, we introduce the Embodied Predictive Interoception Coding model, which integrates an anatomical model of corticocortical connections with Bayesian active inference principles, to propose that agranular visceromotor cortices contribute to interoception by issuing interoceptive predictions. We then discuss how disruptions in interoceptive predictions could function as a common vulnerability for mental and physical illness.}, Author = {Barrett, Lisa Feldman and Simmons, W Kyle}, Date-Added = {2017-05-05 19:10:48 +0000}, Date-Modified = {2017-05-05 19:13:47 +0000}, Doi = {10.1038/nrn3950}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {ppc; Neocortex; isocortex; topographic map; Motor Cortex; behavior; review; grants; Perception; wholeBrain}, Mesh = {Awareness; Bayes Theorem; Brain; Cognition; Emotions; Humans; Mental Disorders; Nerve Net; Perception}, Month = {Jul}, Number = {7}, Pages = {419-29}, Pmc = {PMC4731102}, pmid = {26016744}, Pst = {ppublish}, Title = {Interoceptive predictions in the brain}, Volume = {16}, Year = {2015}, url = {papers/Barrett_NatRevNeurosci2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn3950}} @book{Thompson:1917, Address = {Cambridge}, Annote = {LDR 00694cam 22002291 4500 001 9651821 005 20170113093446.0 008 810622s1917 enka 000 0 eng 035 $9(DLC) 18001383 906 $a7$bcbc$coclcrpl$du$encip$f19$gy-gencatlg 010 $a 18001383 035 $a(OCoLC)14786876 040 $aDLC$cDNLM$dMNS$dDLC 050 00 $aQP84$b.T4 060 0 $aQH 511$bT469o 1917 100 1 $aThompson, D'Arcy Wentworth,$d1860-1948. 245 10 $aOn growth and form. 260 $aCambridge [Eng.]$bUniversity press,$c1917. 300 $axv, 793 p.$bill. ;$c22 cm. 650 0 $aGrowth. 985 $eOCLC REPLACEMENT 991 $bc-GenColl$hQP84$i.T4$p00000383296$tCopy 1$wOCLCREP }, Author = {Thompson, D'Arcy Wentworth}, Call-Number = {QP84}, Date-Added = {2017-05-05 19:07:39 +0000}, Date-Modified = {2017-05-05 19:07:39 +0000}, Genre = {Growth}, Library-Id = {18001383}, Publisher = {University press}, Title = {On growth and form}, Year = {1917}, url = {papers/Thompson_1917.pdf}, Bdsk-File-2 = {papers/Thompson_1917.epub}, Bdsk-File-3 = {papers/Thompson_1917.mobi}, Bdsk-File-4 = {papers/Thompson_1917a.pdf}} @article{Uziel:2002, Abstract = {Axon guidance cues of the ephrin ligand family have been hypothesized to regulate the formation of thalamocortical connections, but in vivo evidence for such a role has not been examined directly. To test whether ephrin-mediated repulsive cues participate in sorting the projections originating from distinct thalamic nuclei, we analyzed the organization of somatosensory and anterior cingulate afferents postnatally in mice lacking ephrin-A5 gene expression. Projections from ventrobasal and laterodorsal nuclei to their respective sensory and limbic cortical areas developed normally. However, a portion of limbic thalamic neurons from the laterodorsal nucleus also formed additional projections to somatosensory cortical territories, thus maintaining inappropriate dual projections to multiple cortical regions. These results suggest that ephrin-A5 is not required for the formation of normal cortical projections from the appropriate thalamic nuclei, but rather acts as a guidance cue that restricts limbic thalamic axons from inappropriate neocortical regions.}, Author = {Uziel, Daniela and M{\"u}hlfriedel, Sven and Zarbalis, Kostas and Wurst, Wolfgang and Levitt, Pat and Bolz, J{\"u}rgen}, Date-Added = {2017-05-05 19:04:13 +0000}, Date-Modified = {2017-05-05 19:04:13 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Cell Count; Cerebral Cortex; Ephrin-A5; Fluorescent Dyes; Gyrus Cinguli; Homozygote; Limbic System; Mice; Mice, Knockout; Nervous System Malformations; Neurons; Thalamic Nuclei; Thalamus}, Month = {Nov}, Number = {21}, Pages = {9352-7}, pmid = {12417660}, Pst = {ppublish}, Title = {Miswiring of limbic thalamocortical projections in the absence of ephrin-A5}, Volume = {22}, Year = {2002}, url = {papers/Uziel_JNeurosci2002.pdf}} @article{Donoghue:1982, Abstract = {The first motor (MI) cortex of the rat was identified as the region from which movements could be evoked by the lowest intensity of electrical stimulation. The location of this region was correlated with cytoarchitecture in the frontal and parietal cortex. Two frontal areas can be discerned in Nissl-stained sections: (1) the medial agranular field, marked by a pale-staining layer III and a compact layer II, and (2) the lateral agranular field, which has more homogeneous superficial layers and a broad layer V containing large, densely staining cells. Both of these regions project to the spinal cord and can therefore be included in the somatic sensorimotor cortex. MI in the rat coincides with the lateral agranular field but also overlaps with part of the adjacent granular cortex of the first somatic sensory (SI) representation. We conclude that the rat MI cortex can be identified by microstimulation techniques and by cytoarchitecture in the rat.}, Author = {Donoghue, J P and Wise, S P}, Date-Added = {2017-05-05 19:02:45 +0000}, Date-Modified = {2017-05-05 19:02:45 +0000}, Doi = {10.1002/cne.902120106}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Brain Mapping; Cytoplasmic Granules; Electric Stimulation; Forelimb; Frontal Lobe; Hindlimb; Mechanoreceptors; Motor Activity; Motor Cortex; Neurons; Parietal Lobe; Rats; Somatosensory Cortex; Spinal Cord; Synaptic Transmission}, Month = {Nov}, Number = {1}, Pages = {76-88}, pmid = {6294151}, Pst = {ppublish}, Title = {The motor cortex of the rat: cytoarchitecture and microstimulation mapping}, Volume = {212}, Year = {1982}, url = {papers/Donoghue_JCompNeurol1982.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902120106}} @article{Kozanian:2015, Abstract = {Functional sensory and motor areas in the developing mammalian neocortex are formed through a complex interaction of cortically intrinsic mechanisms, such as gene expression, and cortically extrinsic mechanisms such as those mediated by thalamic input from the senses. Both intrinsic and extrinsic mechanisms are believed to be involved in cortical patterning and the establishment of areal boundaries in early development; however, the nature of the interaction between intrinsic and extrinsic processes is not well understood. In a previous study, we used a perinatal bilateral enucleation mouse model to test some aspects of this interaction by reweighting sensory input to the developing cortex. Visual deprivation at birth resulted in a shift of intraneocortical connections (INCs) that aligned with ectopic ephrin A5 expression in the same location ten days later at postnatal day (P) 10. A prevailing question remained: Does visual deprivation first induce a change in gene expression, followed by a shift in INCs, or vice versa? In the present study, we address this question by investigating the neuroanatomy and patterns of gene expression in post-natal day (P) 1 and 4 mice following bilateral enucleation at birth. Our results demonstrate a rapid reduction in dorsal lateral geniculate nucleus (dLGN) size and ephrin A5 gene expression 24-hours post-enucleation, with more profound effects apparent at P4. The reduced nuclear size and diminished gene expression mirrors subtle changes in ephrin A5 expression evident in P1 and P4 enucleated neocortex, 11 and 8 days prior to natural eye opening, respectively. Somatosensory and visual INCs were indistinguishable between P1 and P4 mice bilaterally enucleated at birth, indicating that perinatal bilateral enucleation initiates a rapid change in gene expression (within one day) followed by an alteration of sensory INCs later on (second postnatal week). With these results, we gain a deeper understanding of how gene expression and sensory input together regulate cortical arealization and plasticity during early development.}, Author = {Kozanian, Olga O and Abbott, Charles W and Huffman, Kelly J}, Date-Added = {2017-05-05 18:50:54 +0000}, Date-Modified = {2017-05-05 18:50:54 +0000}, Doi = {10.1371/journal.pone.0140391}, Journal = {PLoS One}, Journal-Full = {PloS one}, Mesh = {Animals; Embryo, Mammalian; Embryonic Development; Ephrin-A5; Eye Enucleation; Female; Gene Expression Regulation, Developmental; Geniculate Bodies; Mice; Neocortex; Pregnancy; Somatosensory Cortex; Thalamus; Vision, Ocular; Visual Cortex}, Number = {10}, Pages = {e0140391}, Pmc = {PMC4599918}, pmid = {26452243}, Pst = {epublish}, Title = {Rapid Changes in Cortical and Subcortical Brain Regions after Early Bilateral Enucleation in the Mouse}, Volume = {10}, Year = {2015}, url = {papers/Kozanian_PLoSOne2015.PDF}} @article{Shipp:2005, Abstract = {The agranular cortex is an important landmark-anatomically, as the architectural flag of mammalian motor cortex, and historically, as a spur to the development of theories of localization of function. But why, exactly, do agranularity and motor function go together? To address this question, it should be noted that not only does motor cortex lack granular layer four, it also has a relatively thinner layer three. Therefore, it is the two layers which principally constitute the ascending pathways through the sensory (granular) cortex that have regressed in motor cortex: simply stated, motor cortex does not engage in serial reprocessing of incoming sensory data. But why should a granular architecture not be demanded by the downstream relay of motor instructions through the motor cortex? The scant anatomical evidence available regarding laminar patterns suggests that the pathways from frontal and premotor areas to the primary motor cortex actually bear a greater resemblance to the descending, or feedback connections of sensory cortex that avoid the granular layer. The action of feedback connections is generally described as "modulatory" at a cellular level, or "selective" in terms of systems analysis. By contrast, ascending connections may be labelled "driving" or "instructive". Where the motor cortex uses driving inputs, they are most readily identified as sensory signals instructing the visual location of targets and the kinaesthetic state of the body. Visual signals may activate motor concepts, e.g. "mirror neurons", and the motor plan must select the appropriate muscles and forces to put the plan into action, if the decision to move is taken. This, perhaps, is why "driving" motor signals might be inappropriate-the optimal selection and its execution are conditional upon both kinaesthetic and motivational factors. The argument, summarized above, is constructed in honour of Korbinian Brodmann's centenary, and follows two of the fundamental principles of his school of thought: that uniformities in cortical structure, and development imply global conservation of some aspects of function, whereas regional variations in architecture can be used to chart the "organs" of the cortex, and perhaps to understand their functional differences.}, Author = {Shipp, Stewart}, Date-Added = {2017-05-05 18:50:27 +0000}, Date-Modified = {2017-05-05 18:50:27 +0000}, Doi = {10.1098/rstb.2005.1630}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Mesh = {Brain Mapping; Feedback, Physiological; Humans; Models, Neurological; Motor Cortex; Neural Pathways; Visual Cortex}, Month = {Apr}, Number = {1456}, Pages = {797-814}, Pmc = {PMC1569485}, pmid = {15937013}, Pst = {ppublish}, Title = {The importance of being agranular: a comparative account of visual and motor cortex}, Volume = {360}, Year = {2005}, url = {papers/Shipp_PhilosTransRSocLondBBiolSci2005.pdf}} @article{Sigalas:2015, Abstract = {UNLABELLED: Nicotinic acetylcholine receptors (nAChRs) play an important role in the modulation of many cognitive functions but their role in integrated network activity remains unclear. This is at least partly because of the complexity of the cholinergic circuitry and the difficulty in comparing results from in vivo studies obtained under diverse experimental conditions and types of anesthetics. Hence the role of nAChRs in the synchronization of cortical activity during slow-wave sleep is still controversial, with some studies showing they are involved in ACh-dependent EEG desynchronization, and others suggesting that this effect is mediated exclusively by muscarinic receptors. Here we use an in vitro model of endogenous network activity, in the form of recurring self-maintained depolarized states (Up states), which allows us to examine the role of high-affinity nAChRs on network dynamics in a simpler form of the cortical microcircuit. We find that mice lacking nAChRs containing the β2-subunit (β2-nAChRs) have longer and more frequent Up states, and that this difference is eliminated when β2-nAChRs in wild-type mice are blocked. We further show that endogenously released ACh can modulate Up/Down states through the activation of both β2- and α7-containing nAChRs, but through distinct mechanisms: α7-nAChRs affect only the termination of spontaneous Up states, while β2-nAChRs also regulate their generation. Finally we provide evidence that the effects of β2-subunit-containing, but not α7-subunit-containing nAChRs, are mediated through GABAB receptors. To our knowledge this is the first study documenting direct nicotinic modulation of Up/Down state activity. SIGNIFICANCE STATEMENT: Through our experiments we were able to uncover a clear and previously disputed effect of nicotinic signaling in synchronized activity of neuronal networks of the cortex. We show that both high-affinity receptors (containing the β2-subunit, β2-nAChRs) and low-affinity receptors (containing the α7-subunit, α7-nAChRs) can regulate cortical network function exhibited in the form of Up/Down states. We further show that the effects of β2-nAChRs, but not α7-nAChRs, are mediated through the activation of GABAB receptors. These results suggest a possible synthesis of seemingly contradictory results in the literature and could be valuable for informing computational models of cortical function and for guiding the search for therapeutic interventions.}, Author = {Sigalas, Charalambos and Rigas, Pavlos and Tsakanikas, Panagiotis and Skaliora, Irini}, Date-Added = {2017-05-05 18:50:13 +0000}, Date-Modified = {2017-05-05 18:50:13 +0000}, Doi = {10.1523/JNEUROSCI.5222-14.2015}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {barrel cortex; cholinergic; network activity; oscillations; persistent activity; β2-nAChR}, Mesh = {Animals; Cells, Cultured; Cerebral Cortex; Excitatory Postsynaptic Potentials; In Vitro Techniques; Mice; Mice, Knockout; Neurons; Nicotine; Patch-Clamp Techniques; Receptors, Nicotinic; alpha7 Nicotinic Acetylcholine Receptor}, Month = {Aug}, Number = {32}, Pages = {11196-208}, pmid = {26269630}, Pst = {ppublish}, Title = {High-Affinity Nicotinic Receptors Modulate Spontaneous Cortical Up States In Vitro}, Volume = {35}, Year = {2015}, url = {papers/Sigalas_JNeurosci2015.pdf}} @article{Koukouli:2016, Abstract = {The prefrontal cortex (PFC) plays an important role in cognitive processes, including access to consciousness. The PFC receives significant cholinergic innervation and nicotinic acetylcholine receptors (nAChRs) contribute greatly to the effects of acetylcholine signaling. Using in vivo two-photon imaging of both awake and anesthetized mice, we recorded spontaneous, ongoing neuronal activity in layer II/III in the PFC of WT mice and mice deleted for different nAChR subunits. As in humans, this activity is characterized by synchronous ultraslow fluctuations and neuronal synchronicity is disrupted by light general anesthesia. Both the α7 and β2 nAChR subunits play an important role in the generation of ultraslow fluctuations that occur to a different extent during quiet wakefulness and light general anesthesia. The β2 subunit is specifically required for synchronized activity patterns. Furthermore, chronic application of mecamylamine, an antagonist of nAChRs, disrupts the generation of ultraslow fluctuations. Our findings provide new insight into the ongoing spontaneous activity in the awake and anesthetized state, and the role of cholinergic neurotransmission in the orchestration of cognitive functions.}, Author = {Koukouli, Fani and Rooy, Marie and Changeux, Jean-Pierre and Maskos, Uwe}, Date-Added = {2017-05-05 18:50:02 +0000}, Date-Modified = {2017-05-05 18:50:02 +0000}, Doi = {10.1073/pnas.1614417113}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {anesthesia; consciousness; nicotinic receptor; prefrontal cortex; ultraslow fluctuations}, Month = {Dec}, Number = {51}, Pages = {14823-14828}, Pmc = {PMC5187677}, pmid = {27911815}, Pst = {ppublish}, Title = {Nicotinic receptors in mouse prefrontal cortex modulate ultraslow fluctuations related to conscious processing}, Volume = {113}, Year = {2016}, url = {papers/Koukouli_ProcNatlAcadSciUSA2016.pdf}} @article{Cancedda:2012, Abstract = {The Italian Space Agency, in line with its scientific strategies and the National Utilization Plan for the International Space Station (ISS), contracted Thales Alenia Space Italia to design and build a spaceflight payload for rodent research on ISS: the Mice Drawer System (MDS). The payload, to be integrated inside the Space Shuttle middeck during transportation and inside the Express Rack in the ISS during experiment execution, was designed to function autonomously for more than 3 months and to involve crew only for maintenance activities. In its first mission, three wild type (Wt) and three transgenic male mice over-expressing pleiotrophin under the control of a bone-specific promoter (PTN-Tg) were housed in the MDS. At the time of launch, animals were 2-months old. MDS reached the ISS on board of Shuttle Discovery Flight 17A/STS-128 on August 28(th), 2009. MDS returned to Earth on November 27(th), 2009 with Shuttle Atlantis Flight ULF3/STS-129 after 91 days, performing the longest permanence of mice in space. Unfortunately, during the MDS mission, one PTN-Tg and two Wt mice died due to health status or payload-related reasons. The remaining mice showed a normal behavior throughout the experiment and appeared in excellent health conditions at landing. During the experiment, the mice health conditions and their water and food consumption were daily checked. Upon landing mice were sacrificed, blood parameters measured and tissues dissected for subsequent analysis. To obtain as much information as possible on microgravity-induced tissue modifications, we organized a Tissue Sharing Program: 20 research groups from 6 countries participated. In order to distinguish between possible effects of the MDS housing conditions and effects due to the near-zero gravity environment, a ground replica of the flight experiment was performed at the University of Genova. Control tissues were collected also from mice maintained on Earth in standard vivarium cages.}, Author = {Cancedda, Ranieri and Liu, Yi and Ruggiu, Alessandra and Tavella, Sara and Biticchi, Roberta and Santucci, Daniela and Schwartz, Silvia and Ciparelli, Paolo and Falcetti, Giancarlo and Tenconi, Chiara and Cotronei, Vittorio and Pignataro, Salvatore}, Date-Added = {2017-05-05 18:49:35 +0000}, Date-Modified = {2017-05-05 18:49:35 +0000}, Doi = {10.1371/journal.pone.0032243}, Journal = {PLoS One}, Journal-Full = {PloS one}, Mesh = {Animals; Bone and Bones; Equipment Design; Female; Humans; Male; Mice; Space Flight; Time Factors; Weightlessness Simulation}, Number = {5}, Pages = {e32243}, Pmc = {PMC3362598}, pmid = {22666312}, Pst = {ppublish}, Title = {The Mice Drawer System (MDS) experiment and the space endurance record-breaking mice}, Volume = {7}, Year = {2012}, url = {papers/Cancedda_PLoSOne2012.PDF}} @article{Hawrylycz:2016, Abstract = {The scientific mission of the Project MindScope is to understand neocortex, the part of the mammalian brain that gives rise to perception, memory, intelligence, and consciousness. We seek to quantitatively evaluate the hypothesis that neocortex is a relatively homogeneous tissue, with smaller functional modules that perform a common computational function replicated across regions. We here focus on the mouse as a mammalian model organism with genetics, physiology, and behavior that can be readily studied and manipulated in the laboratory. We seek to describe the operation of cortical circuitry at the computational level by comprehensively cataloging and characterizing its cellular building blocks along with their dynamics and their cell type-specific connectivities. The project is also building large-scale experimental platforms (i.e., brain observatories) to record the activity of large populations of cortical neurons in behaving mice subject to visual stimuli. A primary goal is to understand the series of operations from visual input in the retina to behavior by observing and modeling the physical transformations of signals in the corticothalamic system. We here focus on the contribution that computer modeling and theory make to this long-term effort.}, Author = {Hawrylycz, Michael and Anastassiou, Costas and Arkhipov, Anton and Berg, Jim and Buice, Michael and Cain, Nicholas and Gouwens, Nathan W and Gratiy, Sergey and Iyer, Ramakrishnan and Lee, Jung Hoon and Mihalas, Stefan and Mitelut, Catalin and Olsen, Shawn and Reid, R Clay and Teeter, Corinne and de Vries, Saskia and Waters, Jack and Zeng, Hongkui and Koch, Christof and {MindScope}}, Date-Added = {2017-05-05 18:48:49 +0000}, Date-Modified = {2017-05-05 18:48:49 +0000}, Doi = {10.1073/pnas.1512901113}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {computation; neocortex; neural coding; simulation; visual system}, Month = {Jul}, Number = {27}, Pages = {7337-44}, Pmc = {PMC4941493}, pmid = {27382147}, Pst = {ppublish}, Title = {Inferring cortical function in the mouse visual system through large-scale systems neuroscience}, Volume = {113}, Year = {2016}, url = {papers/Hawrylycz_ProcNatlAcadSciUSA2016.pdf}} @article{Chen:2008a, Abstract = {Pyramidal neurons in the deep layers of the cerebral cortex can be classified into two major classes: callosal projection neurons and long-range subcortical neurons. We and others have shown that a gene expressed specifically by subcortical projection neurons, Fezf2, is required for the formation of axonal projections to the spinal cord, tectum, and pons. Here, we report that Fezf2 regulates a decision between subcortical vs. callosal projection neuron fates. Fezf2(-/-) neurons adopt the fate of callosal projection neurons as assessed by their axonal projections, electrophysiological properties, and acquisition of Satb2 expression. Ctip2 is a major downstream effector of Fezf2 in regulating the extension of axons toward subcortical targets and can rescue the axonal phenotype of Fezf2 mutants. When ectopically expressed, either Fezf2 or Ctip2 can alter the axonal targeting of corticocortical projection neurons and cause them to project to subcortical targets, although Fezf2 can promote a subcortical projection neuron fate in the absence of Ctip2 expression.}, Author = {Chen, Bin and Wang, Song S and Hattox, Alexis M and Rayburn, Helen and Nelson, Sacha B and McConnell, Susan K}, Date-Added = {2017-05-05 18:48:06 +0000}, Date-Modified = {2017-05-05 18:48:06 +0000}, Doi = {10.1073/pnas.0804918105}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Axons; DNA-Binding Proteins; Gene Expression Regulation; Mice; Mice, Mutant Strains; Nerve Tissue Proteins; Phenotype; Pyramidal Cells; Repressor Proteins; Tumor Suppressor Proteins}, Month = {Aug}, Number = {32}, Pages = {11382-7}, Pmc = {PMC2495013}, pmid = {18678899}, Pst = {ppublish}, Title = {The Fezf2-Ctip2 genetic pathway regulates the fate choice of subcortical projection neurons in the developing cerebral cortex}, Volume = {105}, Year = {2008}, url = {papers/Chen_ProcNatlAcadSciUSA2008.pdf}} @article{Hattox:2007, Abstract = {Layer V pyramidal neurons are anatomically and physiologically heterogeneous and project to multiple intracortical and subcortical targets. However, because most physiological studies of layer V pyramidal neurons have been carried out on unidentified cells, we know little about how anatomical and physiological properties relate to subcortical projection site. Here we combine neuroanatomical tract tracing with whole cell recordings in mouse somatosensory cortex to test whether neurons with the same projection target form discrete subpopulations and whether they have stereotyped physiological properties. Our findings indicate that corticothalamic and -trigeminal neurons are two largely nonoverlapping subpopulations, whereas callosal and corticostriatal neurons overlap extensively. The morphology as well as the intrinsic membrane and firing properties of corticothalamic and corticotrigeminal neurons differ from those of callosal and corticostriatal neurons. In addition, we find that each class of projection neuron exhibits a unique compliment of hyperpolarizing and depolarizing afterpotentials that further suggests that cortical neurons with different subcortical targets are distinct from one another.}, Author = {Hattox, Alexis M and Nelson, Sacha B}, Date-Added = {2017-05-05 18:47:26 +0000}, Date-Modified = {2017-05-05 18:47:53 +0000}, Doi = {10.1152/jn.00397.2007}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Mesh = {Action Potentials; Animals; Corpus Callosum; Electrophysiology; Image Processing, Computer-Assisted; Immunohistochemistry; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Nerve Tissue Proteins; Neural Pathways; Nuclear Proteins; Patch-Clamp Techniques; Pyramidal Cells; Somatosensory Cortex; Thalamus; Trigeminal Nerve}, Month = {Dec}, Number = {6}, Pages = {3330-40}, pmid = {17898147}, Pst = {ppublish}, Title = {Layer V neurons in mouse cortex projecting to different targets have distinct physiological properties}, Volume = {98}, Year = {2007}, url = {papers/Hattox_JNeurophysiol2007a.pdf}} @article{Sestan:2001, Abstract = {The visual cortex in primates is parcellated into cytoarchitectonically, physiologically, and connectionally distinct areas: the striate cortex (V1) and the extrastriate cortex, consisting of V2 and numerous higher association areas [1]. The innervation of distinct visual cortical areas by the thalamus is especially segregated in primates, such that the lateral geniculate (LG) nucleus specifically innervates striate cortex, whereas pulvinar projections are confined to extrastriate cortex [2--8]. The molecular bases for the parcellation of the visual cortex and thalamus, as well as the establishment of reciprocal connections between distinct compartments within these two structures, are largely unknown. Here, we show that prospective visual cortical areas and corresponding thalamic nuclei in the embryonic rhesus monkey (Macaca mulatta) can be defined by combinatorial expression of genes encoding Eph receptor tyrosine kinases and their ligands, the ephrins, prior to obvious cytoarchitectonic differentiation within the cortical plate and before the establishment of reciprocal connections between the cortical plate and thalamus. These results indicate that molecular patterns of presumptive visual compartments in both the cortex and thalamus can form independently of one another and suggest a role for EphA family members in both compartment formation and axon guidance within the visual thalamocortical system.}, Author = {Sestan, N and Rakic, P and Donoghue, M J}, Date-Added = {2017-05-05 18:47:03 +0000}, Date-Modified = {2017-05-05 18:47:03 +0000}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Mesh = {Animals; Gene Expression Regulation, Developmental; Macaca; Nerve Tissue Proteins; Receptor Protein-Tyrosine Kinases; Thalamus; Visual Cortex}, Month = {Jan}, Number = {1}, Pages = {39-43}, pmid = {11166178}, Pst = {ppublish}, Title = {Independent parcellation of the embryonic visual cortex and thalamus revealed by combinatorial Eph/ephrin gene expression}, Volume = {11}, Year = {2001}, url = {papers/Sestan_CurrBiol2001.pdf}} @article{Bopp:2014, Abstract = {One of the hallmarks of neocortical circuits is the predominance of recurrent excitation between pyramidal neurons, which is balanced by recurrent inhibition from smooth GABAergic neurons. It has been previously described that in layer 2/3 of primary visual cortex (V1) of cat and monkey, pyramidal cells filled with horseradish peroxidase connect approximately in proportion to the spiny (excitatory, 95% and 81%, respectively) and smooth (GABAergic, 5% and 19%, respectively) dendrites found in the neuropil. By contrast, a recent ultrastructural study of V1 in a single mouse found that smooth neurons formed 51% of the targets of the superficial layer pyramidal cells. This suggests that either the neuropil of this particular mouse V1 had a dramatically different composition to that of V1 in cat and monkey, or that smooth neurons were specifically targeted by the pyramidal cells in that mouse. We tested these hypotheses by examining similar cells filled with biocytin in a sample of five mice. We found that the average composition of the neuropil in V1 of these mice was similar to that described for cat and monkey V1, but that the superficial layer pyramidal cells do form proportionately more synapses with smooth dendrites than the equivalent neurons in cat or monkey. These distributions may underlie the distinct differences in functional architecture of V1 between rodent and higher mammals.}, Author = {Bopp, Rita and Ma{\c c}arico da Costa, Nuno and Kampa, Bj{\"o}rn M and Martin, Kevan A C and Roth, Morgane M}, Date-Added = {2017-05-05 18:45:28 +0000}, Date-Modified = {2017-05-05 18:45:28 +0000}, Doi = {10.1371/journal.pbio.1001932}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Mesh = {Animals; Axons; Cats; Dendritic Spines; Electroporation; GABAergic Neurons; Haplorhini; Mice; Models, Neurological; Presynaptic Terminals; Pyramidal Cells; Visual Cortex}, Month = {Aug}, Number = {8}, Pages = {e1001932}, Pmc = {PMC4138028}, pmid = {25137065}, Pst = {epublish}, Title = {Pyramidal cells make specific connections onto smooth (GABAergic) neurons in mouse visual cortex}, Volume = {12}, Year = {2014}, url = {papers/Bopp_PLoSBiol2014.PDF}} @article{Alcamo:2008, Abstract = {Satb2 is a DNA-binding protein that regulates chromatin organization and gene expression. In the developing brain, Satb2 is expressed in cortical neurons that extend axons across the corpus callosum. To assess the role of Satb2 in neurons, we analyzed mice in which the Satb2 locus was disrupted by insertion of a LacZ gene. In mutant mice, beta-galactosidase-labeled axons are absent from the corpus callosum and instead descend along the corticospinal tract. Satb2 mutant neurons acquire expression of Ctip2, a transcription factor that is necessary and sufficient for the extension of subcortical projections by cortical neurons. Conversely, ectopic expression of Satb2 in neural stem cells markedly decreases Ctip2 expression. Finally, we find that Satb2 binds directly to regulatory regions of Ctip2 and induces changes in chromatin structure. These data suggest that Satb2 functions as a repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex.}, Author = {Alcamo, Elizabeth A and Chirivella, Laura and Dautzenberg, Marcel and Dobreva, Gergana and Fari{\~n}as, Isabel and Grosschedl, Rudolf and McConnell, Susan K}, Date-Added = {2017-05-05 18:44:08 +0000}, Date-Modified = {2017-05-05 18:45:16 +0000}, Doi = {10.1016/j.neuron.2007.12.012}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Animals, Newborn; Bromodeoxyuridine; Cells, Cultured; Cerebral Cortex; Chromatin Immunoprecipitation; Electrophoretic Mobility Shift Assay; Embryo, Mammalian; Gene Expression Regulation, Developmental; Matrix Attachment Region Binding Proteins; Mice; Mice, Transgenic; Mutation; Nerve Tissue Proteins; Neural Pathways; Neurons; Stem Cells; Transcription Factors}, Month = {Feb}, Number = {3}, Pages = {364-77}, pmid = {18255030}, Pst = {ppublish}, Title = {Satb2 regulates callosal projection neuron identity in the developing cerebral cortex}, Volume = {57}, Year = {2008}, url = {papers/Alcamo_Neuron2008.pdf}, Bdsk-File-2 = {papers/Alcamo_Neuron2008a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.12.012}} @article{Rosa:2005, Abstract = {In this paper, we review evidence from comparative studies of primate cortical organization, highlighting recent findings and hypotheses that may help us to understand the rules governing evolutionary changes of the cortical map and the process of formation of areas during development. We argue that clear unequivocal views of cortical areas and their homologies are more likely to emerge for "core" fields, including the primary sensory areas, which are specified early in development by precise molecular identification steps. In primates, the middle temporal area is probably one of these primordial cortical fields. Areas that form at progressively later stages of development correspond to progressively more recent evolutionary events, their development being less firmly anchored in molecular specification. The certainty with which areal boundaries can be delimited, and likely homologies can be assigned, becomes increasingly blurred in parallel with this evolutionary/developmental sequence. For example, while current concepts for the definition of cortical areas have been vindicated in allowing a clarification of the organization of the New World monkey "third tier" visual cortex (the third and dorsomedial areas, V3 and DM), our analyses suggest that more flexible mapping criteria may be needed to unravel the organization of higher-order visual association and polysensory areas.}, Author = {Rosa, Marcello G P and Tweedale, Rowan}, Date-Added = {2017-05-05 18:42:44 +0000}, Date-Modified = {2017-05-05 18:42:44 +0000}, Doi = {10.1098/rstb.2005.1626}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Mesh = {Anatomy, Comparative; Animals; Biological Evolution; Brain Mapping; Models, Biological; Physiology, Comparative; Primates; Visual Cortex; Visual Perception}, Month = {Apr}, Number = {1456}, Pages = {665-91}, Pmc = {PMC1874231}, pmid = {15937007}, Pst = {ppublish}, Title = {Brain maps, great and small: lessons from comparative studies of primate visual cortical organization}, Volume = {360}, Year = {2005}, url = {papers/Rosa_PhilosTransRSocLondBBiolSci2005.pdf}} @article{Villar-Cervino:2013, Abstract = {Cajal-Retzius (CR) cells play a fundamental role in the development of the mammalian cerebral cortex. They control the formation of cortical layers by regulating the migration of pyramidal cells through the release of Reelin. The function of CR cells critically depends on their regular distribution throughout the surface of the cortex, but little is known about the events controlling this phenomenon. Using time-lapse video microscopy in vivo and in vitro, we found that movement of CR cells is regulated by repulsive interactions, which leads to their random dispersion throughout the cortical surface. Mathematical modeling reveals that contact repulsion is both necessary and sufficient for this process, which demonstrates that complex neuronal assemblies may emerge during development through stochastic events. At the molecular level, we found that contact repulsion is mediated by Eph/ephrin interactions. Our observations reveal a mechanism that controls the even distribution of neurons in the developing brain.}, Author = {Villar-Cervi{\~n}o, Verona and Molano-Maz{\'o}n, Manuel and Catchpole, Timothy and Valdeolmillos, Miguel and Henkemeyer, Mark and Mart{\'\i}nez, Luis M and Borrell, V{\'\i}ctor and Mar{\'\i}n, Oscar}, Date-Added = {2017-05-05 16:52:27 +0000}, Date-Modified = {2017-05-05 16:52:27 +0000}, Doi = {10.1016/j.neuron.2012.11.023}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Age Factors; Animals; Body Patterning; Calbindin 2; Cell Movement; Cerebral Cortex; Embryo, Mammalian; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Nerve Tissue Proteins; Neurons; Organ Culture Techniques; Receptor, EphB1; Receptor, EphB2; Receptor, EphB3; S100 Calcium Binding Protein G}, Month = {Feb}, Number = {3}, Pages = {457-71}, Pmc = {PMC3569744}, pmid = {23395373}, Pst = {ppublish}, Title = {Contact repulsion controls the dispersion and final distribution of Cajal-Retzius cells}, Volume = {77}, Year = {2013}, url = {papers/Villar-Cerviño_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.11.023}} @article{Tessier-Lavigne:1995, Author = {Tessier-Lavigne, M}, Date-Added = {2017-05-05 16:24:40 +0000}, Date-Modified = {2017-05-05 16:25:53 +0000}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {review; Development; Protein-Tyrosine Kinases; Ephrin-A2; circuit formation; Brain Mapping; Animals; Proteins;Neurons;Axons}, Mesh = {Animals; Axons; Brain Mapping; Ephrin-A2; Neurons; Protein-Tyrosine Kinases; Proteins}, Month = {Aug}, Number = {3}, Pages = {345-8}, pmid = {7634322}, Pst = {ppublish}, Title = {Eph receptor tyrosine kinases, axon repulsion, and the development of topographic maps}, Volume = {82}, Year = {1995}, url = {papers/Tessier-Lavigne_Cell1995.pdf}} @article{Lieberoth:2009, Abstract = {Although carbohydrates have been implicated in cell interactions in the nervous system, the molecular bases of their functions have remained largely obscure. Here, we show that promotion or inhibition of neurite outgrowth of cerebellar or dorsal root ganglion neurons, respectively, induced by the mucin-type adhesion molecule CD24 depends on alpha2,3-linked sialic acid and Lewis(x) present on glia-specific CD24 glycoforms. Alpha2,3-sialyl residues of CD24 bind to a structural motif in the first fibronectin type III domain of the adhesion molecule L1. Following the observation that the adhesion molecules TAG-1 and Contactin show sequence homologies with fucose-specific lectins, we obtained evidence that TAG-1 and Contactin mediate Lewis(x)-dependent CD24-induced effects on neurite outgrowth. Thus, L1, TAG-1, and Contactin function as lectin-like neuronal receptors. Their cis interactions with neighboring adhesion molecules, e.g., Caspr1 and Caspr2, and with their triggered signal transduction pathways elicit cell type-specific promotion or inhibition of neurite outgrowth induced by glial CD24 in a glycan-dependent trans interaction.}, Author = {Lieberoth, Annika and Splittstoesser, Frauke and Katagihallimath, Nainesh and Jakovcevski, Igor and Loers, Gabriele and Ranscht, Barbara and Karagogeos, Domna and Schachner, Melitta and Kleene, Ralf}, Date-Added = {2017-05-04 23:34:33 +0000}, Date-Modified = {2017-05-04 23:34:33 +0000}, Doi = {10.1523/JNEUROSCI.4361-08.2009}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Animals, Newborn; Antigens, CD15; Antigens, CD24; Binding Sites; Cell Adhesion Molecules, Neuronal; Cells, Cultured; Cerebellum; Contactin 2; Contactins; Cricetinae; Cricetulus; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Ganglia, Spinal; Glycosylation; Immunoprecipitation; Leukocyte L1 Antigen Complex; Locomotion; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurites; Neurons; Peptides; Protein Binding; Recovery of Function; Sialic Acids; Spinal Cord Injuries; Transfection}, Month = {May}, Number = {20}, Pages = {6677-90}, pmid = {19458237}, Pst = {ppublish}, Title = {Lewis(x) and alpha2,3-sialyl glycans and their receptors TAG-1, Contactin, and L1 mediate CD24-dependent neurite outgrowth}, Volume = {29}, Year = {2009}, url = {papers/Lieberoth_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4361-08.2009}} @article{Vernes:2008, Abstract = {BACKGROUND: Rare mutations affecting the FOXP2 transcription factor cause a monogenic speech and language disorder. We hypothesized that neural pathways downstream of FOXP2 influence more common phenotypes, such as specific language impairment. METHODS: We performed genomic screening for regions bound by FOXP2 using chromatin immunoprecipitation, which led us to focus on one particular gene that was a strong candidate for involvement in language impairments. We then tested for associations between single-nucleotide polymorphisms (SNPs) in this gene and language deficits in a well-characterized set of 184 families affected with specific language impairment. RESULTS: We found that FOXP2 binds to and dramatically down-regulates CNTNAP2, a gene that encodes a neurexin and is expressed in the developing human cortex. On analyzing CNTNAP2 polymorphisms in children with typical specific language impairment, we detected significant quantitative associations with nonsense-word repetition, a heritable behavioral marker of this disorder (peak association, P=5.0x10(-5) at SNP rs17236239). Intriguingly, this region coincides with one associated with language delays in children with autism. CONCLUSIONS: The FOXP2-CNTNAP2 pathway provides a mechanistic link between clinically distinct syndromes involving disrupted language.}, Author = {Vernes, Sonja C and Newbury, Dianne F and Abrahams, Brett S and Winchester, Laura and Nicod, J{\'e}r{\^o}me and Groszer, Matthias and Alarc{\'o}n, Maricela and Oliver, Peter L and Davies, Kay E and Geschwind, Daniel H and Monaco, Anthony P and Fisher, Simon E}, Date-Added = {2017-05-04 23:31:28 +0000}, Date-Modified = {2017-05-04 23:31:28 +0000}, Doi = {10.1056/NEJMoa0802828}, Journal = {N Engl J Med}, Journal-Full = {The New England journal of medicine}, Mesh = {Child; Chromatin Immunoprecipitation; Down-Regulation; Female; Forkhead Transcription Factors; Gene Expression Regulation; Genetic Markers; Genome-Wide Association Study; Haplotypes; Humans; Language Development Disorders; Male; Membrane Proteins; Nerve Tissue Proteins; Phenotype; Polymerase Chain Reaction; Polymorphism, Single Nucleotide}, Month = {Nov}, Number = {22}, Pages = {2337-45}, Pmc = {PMC2756409}, pmid = {18987363}, Pst = {ppublish}, Title = {A functional genetic link between distinct developmental language disorders}, Volume = {359}, Year = {2008}, url = {papers/Vernes_NEnglJMed2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1056/NEJMoa0802828}} @article{Strauss:2006, Abstract = {Contactin-associated protein-like 2 (CASPR2) is encoded by CNTNAP2 and clusters voltage-gated potassium channels (K(v)1.1) at the nodes of Ranvier. We report a homozygous mutation of CNTNAP2 in Old Order Amish children with cortical dysplasia, focal epilepsy, relative macrocephaly, and diminished deep-tendon reflexes. Intractable focal seizures began in early childhood, after which language regression, hyperactivity, impulsive and aggressive behavior, and mental retardation developed in all children. Resective surgery did not prevent the recurrence of seizures. Temporal-lobe specimens showed evidence of abnormalities of neuronal migration and structure, widespread astrogliosis, and reduced expression of CASPR2.}, Author = {Strauss, Kevin A and Puffenberger, Erik G and Huentelman, Matthew J and Gottlieb, Steven and Dobrin, Seth E and Parod, Jennifer M and Stephan, Dietrich A and Morton, D Holmes}, Date-Added = {2017-05-04 23:20:58 +0000}, Date-Modified = {2017-05-04 23:20:58 +0000}, Doi = {10.1056/NEJMoa052773}, Journal = {N Engl J Med}, Journal-Full = {The New England journal of medicine}, Mesh = {Child; Child, Preschool; Electroencephalography; Epilepsies, Partial; Gene Expression; Homozygote; Humans; Magnetic Resonance Angiography; Membrane Proteins; Mutation; Nerve Tissue Proteins; Phenotype; Reflex, Stretch; Secondary Prevention; Seizures; Temporal Lobe}, Month = {Mar}, Number = {13}, Pages = {1370-7}, pmid = {16571880}, Pst = {ppublish}, Title = {Recessive symptomatic focal epilepsy and mutant contactin-associated protein-like 2}, Volume = {354}, Year = {2006}, url = {papers/Strauss_NEnglJMed2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1056/NEJMoa052773}} @article{Baudouin:2010, Author = {Baudouin, St{\'e}phane and Scheiffele, Peter}, Date-Added = {2017-05-04 23:08:18 +0000}, Date-Modified = {2017-05-04 23:08:18 +0000}, Doi = {10.1016/j.cell.2010.05.024}, Journal = {Cell}, Journal-Full = {Cell}, Mesh = {Animals; Cell Adhesion Molecules, Neuronal; Humans; Protein Binding; Protein Isoforms; Receptors, Cell Surface; Synapses}, Month = {May}, Number = {5}, Pages = {908, 908.e1}, pmid = {20510934}, Pst = {ppublish}, Title = {SnapShot: Neuroligin-neurexin complexes}, Volume = {141}, Year = {2010}, url = {papers/Baudouin_Cell2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2010.05.024}} @article{Lepe-Zuniga:1987, Author = {Lepe-Zuniga, J L and Zigler, Jr, J S and Gery, I}, Date-Added = {2017-05-04 21:46:52 +0000}, Date-Modified = {2017-05-04 21:46:52 +0000}, Journal = {J Immunol Methods}, Journal-Full = {Journal of immunological methods}, Mesh = {Culture Media; HEPES; Hydrogen Peroxide; Piperazines}, Month = {Oct}, Number = {1}, Pages = {145}, pmid = {3655381}, Pst = {ppublish}, Title = {Toxicity of light-exposed Hepes media}, Volume = {103}, Year = {1987}} @article{Moreno-Juan:2017, Abstract = {The cerebral cortex is organized into specialized sensory areas, whose initial territory is determined by intracortical molecular determinants. Yet, sensory cortical area size appears to be fine tuned during development to respond to functional adaptations. Here we demonstrate the existence of a prenatal sub-cortical mechanism that regulates the cortical areas size in mice. This mechanism is mediated by spontaneous thalamic calcium waves that propagate among sensory-modality thalamic nuclei up to the cortex and that provide a means of communication among sensory systems. Wave pattern alterations in one nucleus lead to changes in the pattern of the remaining ones, triggering changes in thalamic gene expression and cortical area size. Thus, silencing calcium waves in the auditory thalamus induces Rorβ upregulation in a neighbouring somatosensory nucleus preluding the enlargement of the barrel-field. These findings reveal that embryonic thalamic calcium waves coordinate cortical sensory area patterning and plasticity prior to sensory information processing.}, Annote = {- evidence for thalamocortical inputs in regulating size of cortical areas through - evidence for prenatal thalamic waves is all from in vitro thalamic slice recordings in gcamp6 expression thalamic cell populations. In slice the wave travel between thalamic nuclei quote: >Our finding that thalamic waves emerge before peripheral input reaches the thalamus (see also ref. 46) indicates that they might be intrinsically generated in this structure. ref 46 is Pouchelon:2012 (Eur J Neurosci). However the referenced paper is a review of only somatosensory system axon growth. No information on functional innervation of thalamic nuclei by the brainstem. Confusingly, the next sentence in reference to their brain slice thalamic waves: >spontaneous calcium waves persist in the absence of retinal input, although their pattern and frequency is altered if no axons from this organ are received. So peripheral input is functionally influencing the thalamus in their model then? }, Author = {Moreno-Juan, Ver{\'o}nica and Filipchuk, Anton and Ant{\'o}n-Bola{\~n}os, Noelia and Mezzera, Cecilia and Gezelius, Henrik and Andr{\'e}s, Belen and Rodr{\'\i}guez-Malmierca, Luis and Sus{\'\i}n, Rafael and Schaad, Olivier and Iwasato, Takuji and Sch{\"u}le, Roland and Rutlin, Michael and Nelson, Sacha and Ducret, Sebastien and Valdeolmillos, Miguel and Rijli, Filippo M and L{\'o}pez-Bendito, Guillermina}, Date-Added = {2017-05-04 20:45:39 +0000}, Date-Modified = {2018-01-25 01:19:19 +0000}, Doi = {10.1038/ncomms14172}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Month = {Feb}, Pages = {14172}, Pmc = {PMC5296753}, pmid = {28155854}, Pst = {epublish}, Title = {Prenatal thalamic waves regulate cortical area size prior to sensory processing}, Volume = {8}, Year = {2017}, url = {papers/Moreno-Juan_NatCommun2017.pdf}} @article{Bray:1979, Abstract = {Evidence is presented that (a) the growth cone of cultured neurons can exert mechanical tension, and (b) that the direction of advance of the growth cone is determined by the tension existing between it and the rest of the cell. (a) The evidence that growth cones can pull comes from a vectorial analysis of the outlines of individually isolated sensory neurons. The angles formed in these outgrowths are very close to those of tension-generated networks anchored at their free ends and these values are restored shortly after an experimental displacement. The relative mechanical tension on each segment of an outgrowth can be calculated by standard methods and is found to decrease at each branch point. It appears to be correlated with the diameter of the fibre so that thicker fibres maintain more tension than thinner ones. (b) The influence of tension on the direction of advance of the growth cone is shown by 2 kinds of experient. If a growing neurite is pulled to one side with a microelectrode then the direction of its advance is changed immediately according to the new stress. If the mechanical tension on the growth cone of a neurite is released by amputation or displacement the growth cone is found to have a high probability of branching shortly afterwards. The ability of the growth cone to exert tension is discussed in relation to evidence that microspikes have contractile properties and in terms of the distribution of microfilaments within the neurite. It is suggested that the exertion of tension by a growth cone could serve to guide the neurite along paths of high adhesivity both in vitro and in vivo.}, Author = {Bray, D}, Date-Added = {2017-05-03 23:05:39 +0000}, Date-Modified = {2017-05-03 23:05:39 +0000}, Journal = {J Cell Sci}, Journal-Full = {Journal of cell science}, Mesh = {Animals; Cells, Cultured; Chickens; Microscopy, Electron, Scanning; Neurons; Stress, Mechanical}, Month = {Jun}, Pages = {391-410}, pmid = {479327}, Pst = {ppublish}, Title = {Mechanical tension produced by nerve cells in tissue culture}, Volume = {37}, Year = {1979}, url = {papers/Bray_JCellSci1979.pdf}} @article{Chklovskii:2004a, Abstract = {In mammalian visual cortex, neurons are organized according to their functional properties into multiple maps such as retinotopic, ocular dominance, orientation preference, direction of motion, and others. What determines the organization of cortical maps? We argue that cortical maps reflect neuronal connectivity in intracortical circuits. Because connecting distant neurons requires costly wiring (i.e., axons and dendrites), there is an evolutionary pressure to place connected neurons as close to each other as possible. Then, cortical maps may be viewed as solutions that minimize wiring cost for given intracortical connectivity. These solutions can help us in inferring intracortical connectivity and, ultimately, in understanding the function of the visual system.}, Author = {Chklovskii, Dmitri B and Koulakov, Alexei A}, Date-Added = {2017-05-02 18:52:58 +0000}, Date-Modified = {2017-05-02 18:52:58 +0000}, Doi = {10.1146/annurev.neuro.27.070203.144226}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Mesh = {Animals; Axons; Brain Mapping; Dendrites; Humans; Nerve Net; Neural Pathways; Visual Cortex; Visual Fields; Visual Pathways}, Pages = {369-92}, pmid = {15217337}, Pst = {ppublish}, Title = {Maps in the brain: what can we learn from them?}, Volume = {27}, Year = {2004}, url = {papers/Chklovskii_AnnuRevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.27.070203.144226}} @article{Zalesky:2012, Abstract = {Numerous studies have demonstrated that brain networks derived from neuroimaging data have nontrivial topological features, such as small-world organization, modular structure and highly connected hubs. In these studies, the extent of connectivity between pairs of brain regions has often been measured using some form of statistical correlation. This article demonstrates that correlation as a measure of connectivity in and of itself gives rise to networks with non-random topological features. In particular, networks in which connectivity is measured using correlation are inherently more clustered than random networks, and as such are more likely to be small-world networks. Partial correlation as a measure of connectivity also gives rise to networks with non-random topological features. Partial correlation networks are inherently less clustered than random networks. Network measures in correlation networks should be benchmarked against null networks that respect the topological structure induced by correlation measurements. Prevalently used random rewiring algorithms do not yield appropriate null networks for some network measures. Null networks are proposed to explicitly normalize for the inherent topological structure found in correlation networks, resulting in more conservative estimates of small-world organization. A number of steps may be needed to normalize each network measure individually and control for distinct features (e.g. degree distribution). The main conclusion of this article is that correlation can and should be used to measure connectivity, however appropriate null networks should be used to benchmark network measures in correlation networks.}, Author = {Zalesky, Andrew and Fornito, Alex and Bullmore, Ed}, Date-Added = {2017-04-29 23:07:08 +0000}, Date-Modified = {2017-04-29 23:07:08 +0000}, Doi = {10.1016/j.neuroimage.2012.02.001}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Mesh = {Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Neural Pathways}, Month = {May}, Number = {4}, Pages = {2096-106}, pmid = {22343126}, Pst = {ppublish}, Title = {On the use of correlation as a measure of network connectivity}, Volume = {60}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2012.02.001}} @article{Fornito:2012, Abstract = {Schizophrenia is frequently characterized as a disorder of brain connectivity. Neuroimaging has played a central role in supporting this view, with nearly two decades of research providing abundant evidence of structural and functional connectivity abnormalities in the disorder. In recent years, our understanding of how schizophrenia affects brain networks has been greatly advanced by attempts to map the complete set of inter-regional interactions comprising the brain's intricate web of connectivity; i.e., the human connectome. Imaging connectomics refers to the use of neuroimaging techniques to generate these maps which, combined with the application of graph theoretic methods, has enabled relatively comprehensive mapping of brain network connectivity and topology in unprecedented detail. Here, we review the application of these techniques to the study of schizophrenia, focusing principally on magnetic resonance imaging (MRI) research, while drawing attention to key methodological issues in the field. The published findings suggest that schizophrenia is associated with a widespread and possibly context-independent functional connectivity deficit, upon which are superimposed more circumscribed, context-dependent alterations associated with transient states of hyper- and/or hypo-connectivity. In some cases, these changes in inter-regional functional coupling dynamics can be related to measures of intra-regional dysfunction. Topological disturbances of functional brain networks in schizophrenia point to reduced local network connectivity and modular structure, as well as increased global integration and network robustness. Some, but not all, of these functional abnormalities appear to have an anatomical basis, though the relationship between the two is complex. By comprehensively mapping connectomic disturbances in patients with schizophrenia across the entire brain, this work has provided important insights into the highly distributed character of neural abnormalities in the disorder, and the potential functional consequences that these disturbances entail.}, Author = {Fornito, Alex and Zalesky, Andrew and Pantelis, Christos and Bullmore, Edward T}, Date-Added = {2017-04-29 23:06:44 +0000}, Date-Modified = {2017-04-29 23:06:44 +0000}, Doi = {10.1016/j.neuroimage.2011.12.090}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Mesh = {Brain Mapping; Connectome; Humans; Magnetic Resonance Imaging; Neural Pathways; Schizophrenia}, Month = {Oct}, Number = {4}, Pages = {2296-314}, pmid = {22387165}, Pst = {ppublish}, Title = {Schizophrenia, neuroimaging and connectomics}, Volume = {62}, Year = {2012}, url = {papers/Fornito_Neuroimage2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2011.12.090}} @article{Chang:2017, Abstract = {Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal.}, Author = {Chang, Liangtang and Zhang, Shikun and Poo, Mu-Ming and Gong, Neng}, Date-Added = {2017-04-25 23:25:40 +0000}, Date-Modified = {2017-04-25 23:25:40 +0000}, Doi = {10.1073/pnas.1620764114}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {bodily self-consciousness; instrumental mirror use; mirror self-recognition; rhesus monkey; visual-proprioceptive association}, Month = {Mar}, Number = {12}, Pages = {3258-3263}, Pmc = {PMC5373394}, pmid = {28193875}, Pst = {ppublish}, Title = {Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images}, Volume = {114}, Year = {2017}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1620764114}} @article{Swartz:2017, Abstract = {Identifying biological mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified epigenetic modification of gene expression as one such mechanism. Recent clinical studies have suggested that epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear whether differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal epigenetic, neuroimaging and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status (SES) predict changes in risk-related brain function. Specifically, we find that lower SES during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention among high-risk individuals.}, Author = {Swartz, J R and Hariri, A R and Williamson, D E}, Date-Added = {2017-04-25 00:10:58 +0000}, Date-Modified = {2017-04-25 00:10:58 +0000}, Doi = {10.1038/mp.2016.82}, Journal = {Mol Psychiatry}, Journal-Full = {Molecular psychiatry}, Month = {Feb}, Number = {2}, Pages = {209-214}, Pmc = {PMC5122474}, pmid = {27217150}, Pst = {ppublish}, Title = {An epigenetic mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents}, Volume = {22}, Year = {2017}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/mp.2016.82}} @article{McGowan:2009, Abstract = {Maternal care influences hypothalamic-pituitary-adrenal (HPA) function in the rat through epigenetic programming of glucocorticoid receptor expression. In humans, childhood abuse alters HPA stress responses and increases the risk of suicide. We examined epigenetic differences in a neuron-specific glucocorticoid receptor (NR3C1) promoter between postmortem hippocampus obtained from suicide victims with a history of childhood abuse and those from either suicide victims with no childhood abuse or controls. We found decreased levels of glucocorticoid receptor mRNA, as well as mRNA transcripts bearing the glucocorticoid receptor 1F splice variant and increased cytosine methylation of an NR3C1 promoter. Patch-methylated NR3C1 promoter constructs that mimicked the methylation state in samples from abused suicide victims showed decreased NGFI-A transcription factor binding and NGFI-A-inducible gene transcription. These findings translate previous results from rat to humans and suggest a common effect of parental care on the epigenetic regulation of hippocampal glucocorticoid receptor expression.}, Author = {McGowan, Patrick O and Sasaki, Aya and D'Alessio, Ana C and Dymov, Sergiy and Labont{\'e}, Benoit and Szyf, Moshe and Turecki, Gustavo and Meaney, Michael J}, Date-Added = {2017-04-25 00:01:42 +0000}, Date-Modified = {2017-04-25 00:01:42 +0000}, Doi = {10.1038/nn.2270}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Adult; Adult Survivors of Child Abuse; Base Sequence; Cell Line; DNA Methylation; Epigenesis, Genetic; Female; Hippocampus; Humans; Male; Middle Aged; Molecular Sequence Data; Promoter Regions, Genetic; Receptors, Glucocorticoid; Suicide; Young Adult}, Month = {Mar}, Number = {3}, Pages = {342-8}, Pmc = {PMC2944040}, pmid = {19234457}, Pst = {ppublish}, Title = {Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse}, Volume = {12}, Year = {2009}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2270}} @article{Costa:2010, Abstract = {The cortical column has been an invaluable concept to explain the functional organization of the neocortex. While this idea was born out of experiments that cleverly combined electrophysiological recordings with anatomy, no one has 'seen' the anatomy of a column. All we know is that when we record through the cortex of primates, ungulates, and carnivores in a trajectory perpendicular to its surface there is a remarkable constancy in the receptive field properties of the neurons regarding one set of stimulus features. There is no obvious morphological analog for this functional architecture, in fact much of the anatomical data seems to challenge it. Here we describe historically the origins of the concept of the cortical column and the struggles of the pioneers to define the columnar architecture. We suggest that in the concept of a 'canonical circuit' we may find the means to reconcile the structure of neocortex with its functional architecture. The canonical microcircuit respects the known connectivity of the neocortex, and it is flexible enough to change transiently the architecture of its network in order to perform the required computations.}, Author = {da Costa, Nuno Ma{\c c}arico and Martin, Kevan A C}, Date-Added = {2017-04-24 20:04:33 +0000}, Date-Modified = {2017-04-24 20:04:33 +0000}, Doi = {10.3389/fnana.2010.00016}, Journal = {Front Neuroanat}, Journal-Full = {Frontiers in neuroanatomy}, Keywords = {Daisy; bouton cluster; canonical microcircuit; cortical column; neuroanatomy}, Pages = {16}, Pmc = {PMC2904586}, pmid = {20640245}, Pst = {epublish}, Title = {Whose Cortical Column Would that Be?}, Volume = {4}, Year = {2010}, url = {papers/Costa_FrontNeuroanat2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fnana.2010.00016}} @article{Fiebig:2017, Abstract = {A dominant theory of working memory (WM), referred to as the persistent activity hypothesis, holds that recurrently connected neural networks, presumably located in the prefrontal cortex, encode and maintain WM memory items through sustained elevated activity. Reexamination of experimental data has shown that prefrontal cortex activity in single units during delay periods is much more variable than predicted by such a theory and associated computational models. Alternative models of WM maintenance based on synaptic plasticity, such as short-term nonassociative (non-Hebbian) synaptic facilitation, have been suggested but cannot account for encoding of novel associations. Here we test the hypothesis that a recently identified fast-expressing form of Hebbian synaptic plasticity (associative short-term potentiation) is a possible mechanism for WM encoding and maintenance. Our simulations using a spiking neural network model of cortex reproduce a range of cognitive memory effects in the classical multi-item WM task of encoding and immediate free recall of word lists. Memory reactivation in the model occurs in discrete oscillatory bursts rather than as sustained activity. We relate dynamic network activity as well as key synaptic characteristics to electrophysiological measurements. Our findings support the hypothesis that fast Hebbian short-term potentiation is a key WM mechanism. SIGNIFICANCE STATEMENT: Working memory (WM) is a key component of cognition. Hypotheses about the neural mechanism behind WM are currently under revision. Reflecting recent findings of fast Hebbian synaptic plasticity in cortex, we test whether a cortical spiking neural network model with such a mechanism can learn a multi-item WM task (word list learning). We show that our model can reproduce human cognitive phenomena and achieve comparable memory performance in both free and cued recall while being simultaneously compatible with experimental data on structure, connectivity, and neurophysiology of the underlying cortical tissue. These findings are directly relevant to the ongoing paradigm shift in the WM field.}, Author = {Fiebig, Florian and Lansner, Anders}, Date-Added = {2017-04-24 19:05:29 +0000}, Date-Modified = {2017-04-24 19:05:29 +0000}, Doi = {10.1523/JNEUROSCI.1989-16.2017}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Hebbian plasticity; primacy; recency; short-term potentiation; word list learning; working memory}, Month = {Jan}, Number = {1}, Pages = {83-96}, Pmc = {PMC5214637}, pmid = {28053032}, Pst = {ppublish}, Title = {A Spiking Working Memory Model Based on Hebbian Short-Term Potentiation}, Volume = {37}, Year = {2017}, url = {papers/Fiebig_JNeurosci2017.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1989-16.2017}} @article{Ramaswamy:2015, Author = {Ramaswamy, Srikanth and Courcol, Jean-Denis and Abdellah, Marwan and Adaszewski, Stanislaw R and Antille, Nicolas and Arsever, Selim and Atenekeng, Guy and Bilgili, Ahmet and Brukau, Yury and Chalimourda, Athanassia and Chindemi, Giuseppe and Delalondre, Fabien and Dumusc, Raphael and Eilemann, Stefan and Gevaert, Michael Emiel and Gleeson, Padraig and Graham, Joe W and Hernando, Juan B and Kanari, Lida and Katkov, Yury and Keller, Daniel and King, James G and Ranjan, Rajnish and Reimann, Michael W and R{\"o}ssert, Christian and Shi, Ying and Shillcock, Julian C and Telefont, Martin and Van Geit, Werner and Diaz, Jafet Villafranca and Walker, Richard and Wang, Yun and Zaninetta, Stefano M and DeFelipe, Javier and Hill, Sean L and Muller, Jeffrey and Segev, Idan and Sch{\"u}rmann, Felix and Muller, Eilif B and Markram, Henry}, Date-Added = {2017-04-24 18:39:12 +0000}, Date-Modified = {2017-04-24 18:39:12 +0000}, Doi = {10.3389/fncir.2015.00044}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {experimental data; ion channels; microcircuit; models; morphologies; neocortex; neurons; synapses}, Mesh = {Animals; Cooperative Behavior; Information Systems; Neocortex; Rats; Somatosensory Cortex}, Pages = {44}, Pmc = {PMC4597797}, pmid = {26500503}, Pst = {epublish}, Title = {The neocortical microcircuit collaboration portal: a resource for rat somatosensory cortex}, Volume = {9}, Year = {2015}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncir.2015.00044}} @article{Kaneko:2013, Abstract = {In spite of recent progress in brain sciences, the local circuit of the cerebral neocortex, including motor areas, still remains elusive. Morphological works on excitatory cortical circuitry from thalamocortical (TC) afferents to corticospinal neurons (CSNs) in motor-associated areas are reviewed here. First, TC axons of motor thalamic nuclei have been re-examined by the single-neuron labeling method. There are middle layer (ML)-targeting and layer (L) 1-preferring TC axon types in motor-associated areas, being analogous to core and matrix types, respectively, of Jones (1998) in sensory areas. However, the arborization of core-like motor TC axons spreads widely and disregards the columnar structure that is the basis of information processing in sensory areas, suggesting that motor areas adopt a different information-processing framework such as area-wide laminar organization. Second, L5 CSNs receive local excitatory inputs not only from L2/3 pyramidal neurons but also from ML spiny neurons, the latter directly processing cerebellar information of core-like TC neurons (TCNs). In contrast, basal ganglia information is targeted to apical dendrites of L2/3 and L5 pyramidal neurons through matrix TCNs. Third, L6 corticothalamic neurons (CTNs) are most densely innervated by ML spiny neurons located just above CTNs. Since CTNs receive only weak connections from L2/3 and L5 pyramidal neurons, the TC recurrent circuit composed of TCNs, ML spiny neurons and CTNs appears relatively independent of the results of processing in L2/3 and L5. It is proposed that two circuits sharing the same TC projection and ML neurons are embedded in the neocortex: one includes L2/3 and L5 neurons, processes afferent information in a feedforward way and sends the processed information to other cortical areas and subcortical regions; and the other circuit participates in a dynamical system of the TC recurrent circuit and may serve as the basis of autonomous activity of the neocortex.}, Author = {Kaneko, Takeshi}, Date-Added = {2017-04-24 18:31:01 +0000}, Date-Modified = {2017-04-24 18:31:01 +0000}, Doi = {10.3389/fncir.2013.00075}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {corticospinal projection neurons; corticothalamic projection neurons; excitatory connection; local circuit; microcircuit; motor cortex; pyramidal neurons; thalamocortical projection}, Mesh = {Animals; Excitatory Postsynaptic Potentials; Humans; Motor Cortex; Nerve Net; Neural Pathways; Neurons; Rats}, Pages = {75}, Pmc = {PMC3664775}, pmid = {23754982}, Pst = {epublish}, Title = {Local connections of excitatory neurons in motor-associated cortical areas of the rat}, Volume = {7}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncir.2013.00075}} @article{Zhang:2004d, Abstract = {Layer V pyramidal neurons in the rat medial prefrontal cortex (PFC) were examined with whole cell patch-clamp recording in acute slices from postnatal day 1 (P1) to P36. In the first few days after birth, layer V pyramidal neurons had low resting potentials, high-input resistance, and long membrane time constant. During the next 2 wk, the resting potential shifted by -14 mV, while the input resistance and time constant decreased by 15- and 4-fold, respectively. Between P3 and P21, the surface area of the cell body doubled, while the total lengths of apical and basal dendrites increased by 5- and 13-fold, respectively. Action potentials (APs) were observed at all aged tested. The peak amplitude of APs increased by 30 mV during the first 3 wk, while AP rise time and half-maximum duration shortened significantly. Compared with neurons at P21 or older, neurons in the first week required much smaller currents to reach their maximum firing frequencies, but the maximum frequencies were lower than those at older ages. Stimulation of layer II/III induced monosynaptic responses in neurons older than P5. Paired-pulse responses showed a short-term depression at P7, which shifted progressive to facilitation at older ages. These results demonstrate that, similar to other neurons in the brain, layer V pyramidal neurons in the PFC undergo a period of rapid development during the first 3 wk after birth. These findings suggest that the intrinsic properties of neurons and the properties of synaptic inputs develop concomitantly during early life.}, Author = {Zhang, Zhong-wei}, Date-Added = {2017-04-24 18:27:39 +0000}, Date-Modified = {2017-04-24 18:27:39 +0000}, Doi = {10.1152/jn.00855.2003}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Mesh = {Action Potentials; Aging; Animals; Dendrites; Electrophysiology; Female; Histocytochemistry; In Vitro Techniques; Lysine; Male; Membrane Potentials; Patch-Clamp Techniques; Prefrontal Cortex; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Synapses}, Month = {Mar}, Number = {3}, Pages = {1171-82}, pmid = {14602839}, Pst = {ppublish}, Title = {Maturation of layer V pyramidal neurons in the rat prefrontal cortex: intrinsic properties and synaptic function}, Volume = {91}, Year = {2004}, url = {papers/Zhang_JNeurophysiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00855.2003}} @article{Sherman:2016, Abstract = {Several challenges to current views of thalamocortical processing are offered here. Glutamatergic pathways in thalamus and cortex are divided into two distinct classes: driver and modulator. We suggest that driver inputs are the main conduits of information and that modulator inputs modify how driver inputs are processed. Different driver sources reveal two types of thalamic relays: first order relays receive subcortical driver input (for example, retinal input to the lateral geniculate nucleus), whereas higher order relays (for example, pulvinar) receive driver input from layer 5 of cortex and participate in cortico-thalamo-cortical (or transthalamic) circuits. These transthalamic circuits represent an unappreciated aspect of cortical functioning, which I discuss here. Direct corticocortical connections are often paralleled by transthalamic ones. Furthermore, driver inputs to thalamus, both first and higher order, typically arrive via branching axons, and the transthalamic branch often innervates subcortical motor centers, leading to the suggestion that these inputs to thalamus serve as efference copies.}, Author = {Sherman, S Murray}, Date-Added = {2017-04-20 21:10:29 +0000}, Date-Modified = {2017-04-20 21:10:29 +0000}, Doi = {10.1038/nn.4269}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Animals; Cerebral Cortex; Glutamic Acid; Humans; Nerve Net; Neural Pathways; Thalamus}, Month = {Apr}, Number = {4}, Pages = {533-41}, pmid = {27021938}, Pst = {ppublish}, Title = {Thalamus plays a central role in ongoing cortical functioning}, Volume = {19}, Year = {2016}, url = {papers/Sherman_NatNeurosci2016.pdf}} @article{Allen:2016, Abstract = {KEY POINTS: The lateral posterior and posterior thalamic nuclei have been implicated in aspects of visually guided behaviour and reflex responses to light, including those dependent on melanopsin photoreception. Here we investigated the extent and basic properties of visually evoked activity across the mouse lateral posterior and posterior thalamus. We show that a subset of retinal projections to these regions derive from melanopsin-expressing retinal ganglion cells and find many cells that exhibit melanopsin-dependent changes in firing. We also show that subsets of cells across these regions integrate signals from both eyes in various ways and that, within the lateral posterior thalamus, visual responses are retinotopically ordered. ABSTRACT: In addition to the primary thalamocortical visual relay in the lateral geniculate nuclei, a number of other thalamic regions contribute to aspects of visual processing. Thus, the lateral posterior thalamic nuclei (LP/pulvinar) appear important for various functions including determining visual saliency, visually guided behaviours and, alongside dorsal portions of the posterior thalamic nuclei (Po), multisensory processing of information related to aversive stimuli. However, despite the growing importance of mice as a model for understanding visual system organisation, at present we know very little about the basic visual response properties of cells in the mouse LP or Po. Prompted by earlier suggestions that melanopsin photoreception might be important for certain functions of these nuclei, we first employ specific viral tracing to show that a subset of retinal projections to the LP derive from melanopsin-expressing retinal ganglion cells. We next use multielectrode electrophysiology to demonstrate that LP and dorsal Po cells exhibit a variety of responses to simple visual stimuli including two distinct classes that express melanopsin-dependent changes in firing (together comprising ∼25% of neurons we recorded). We also show that subgroups of LP/Po cells integrate signals from both eyes in various ways and that, within the LP, visual responses are retinotopically ordered. Together our data reveal a diverse population of visually responsive neurons across the LP and dorsal Po whose properties align with some of the established functions of these nuclei and suggest new possible routes through which melanopsin photoreception could contribute to reflex light responses and/or higher order visual processing.}, Author = {Allen, Annette E and Procyk, Christopher A and Howarth, Michael and Walmsley, Lauren and Brown, Timothy M}, Date-Added = {2017-04-20 21:02:16 +0000}, Date-Modified = {2017-04-20 21:02:16 +0000}, Doi = {10.1113/JP271707}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Animals; Evoked Potentials, Visual; Lateral Thalamic Nuclei; Mice; Mice, Inbred C57BL; Posterior Thalamic Nuclei; Retinal Ganglion Cells; Rod Opsins; Visual Pathways}, Month = {Apr}, Number = {7}, Pages = {1911-29}, Pmc = {PMC4818601}, pmid = {26842995}, Pst = {ppublish}, Title = {Visual input to the mouse lateral posterior and posterior thalamic nuclei: photoreceptive origins and retinotopic order}, Volume = {594}, Year = {2016}, url = {papers/Allen_JPhysiol2016.pdf}} @article{Warner:2015, Abstract = {BACKGROUND: Conscious vision is believed to depend upon an intact primary visual cortex (V1), although injury in early life is often accompanied by the preservation of visual capacity, unlike in adulthood. The middle temporal area (MT) receives input from the retinorecipient koniocellular layers of the lateral geniculate nucleus (LGN) and the more recently described medial subdivision of the inferior pulvinar (PIm) of the thalamus, pathways that potentially contribute to preservation of vision after early damage to V1. RESULTS: We examined the potential of these pathways to the long-term preservation of vision after permanent lesions of primate V1 in early and adult life by using a combination of neural tracing and diffusion MRI. We show that early-life V1 lesions lead to less pruning of the retina-pulvinar-MT pathway than is observed in control or adult lesion animals. CONCLUSIONS: These findings suggest that sustained visual input through the pulvinar to MT following a lesion of V1 in early life has the capacity to afford improved visual outcomes.}, Author = {Warner, Claire E and Kwan, William C and Wright, David and Johnston, Leigh A and Egan, Gary F and Bourne, James A}, Date-Added = {2017-04-20 20:54:32 +0000}, Date-Modified = {2017-04-20 20:54:32 +0000}, Doi = {10.1016/j.cub.2014.12.028}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Mesh = {Age Factors; Animals; Callithrix; Diffusion Magnetic Resonance Imaging; Female; Male; Neuroanatomical Tract-Tracing Techniques; Pulvinar; Vision, Ocular; Visual Cortex; Visual Pathways}, Month = {Feb}, Number = {4}, Pages = {424-34}, pmid = {25601551}, Pst = {ppublish}, Title = {Preservation of vision by the pulvinar following early-life primary visual cortex lesions}, Volume = {25}, Year = {2015}, url = {papers/Warner_CurrBiol2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2014.12.028}} @article{Spitzer:2015, Abstract = {Among the many forms of brain plasticity, changes in synaptic strength and changes in synapse number are particularly prominent. However, evidence for neurotransmitter respecification or switching has been accumulating steadily, both in the developing nervous system and in the adult brain, with observations of transmitter addition, loss, or replacement of one transmitter with another. Natural stimuli can drive these changes in transmitter identity, with matching changes in postsynaptic transmitter receptors. Strikingly, they often convert the synapse from excitatory to inhibitory or vice versa, providing a basis for changes in behavior in those cases in which it has been examined. Progress has been made in identifying the factors that induce transmitter switching and in understanding the molecular mechanisms by which it is achieved. There are many intriguing questions to be addressed.}, Author = {Spitzer, Nicholas C}, Date-Added = {2017-04-19 19:20:51 +0000}, Date-Modified = {2017-04-19 19:20:51 +0000}, Doi = {10.1016/j.neuron.2015.05.028}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Brain; Humans; Neuronal Plasticity; Neurons; Neurotransmitter Agents; Synapses; Synaptic Potentials}, Month = {Jun}, Number = {5}, Pages = {1131-44}, Pmc = {PMC4458710}, pmid = {26050033}, Pst = {ppublish}, Title = {Neurotransmitter Switching? No Surprise}, Volume = {86}, Year = {2015}, url = {papers/Spitzer_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.05.028}} @article{Guemez-Gamboa:2014, Abstract = {Activity-dependent neurotransmitter switching engages genetic programs regulating transmitter synthesis, but the mechanism by which activity is transduced is unknown. We suppressed activity in single neurons in the embryonic spinal cord to determine whether glutamate-gamma-aminobutyric acid (GABA) switching is cell autonomous. Transmitter respecification did not occur, suggesting that it is homeostatically regulated by the level of activity in surrounding neurons. Graded increase in the number of silenced neurons in cultures led to graded decrease in the number of neurons expressing GABA, supporting non-cell-autonomous transmitter switching. We found that brain-derived neurotrophic factor (BDNF) is expressed in the spinal cord during the period of transmitter respecification and that spike activity causes release of BDNF. Activation of TrkB receptors triggers a signaling cascade involving JNK-mediated activation of cJun that regulates tlx3, a glutamate/GABA selector gene, accounting for calcium-spike BDNF-dependent transmitter switching. Our findings identify a molecular mechanism for activity-dependent respecification of neurotransmitter phenotype in developing spinal neurons.}, Author = {Guemez-Gamboa, Alicia and Xu, Lin and Meng, Da and Spitzer, Nicholas C}, Date-Added = {2017-04-19 19:20:49 +0000}, Date-Modified = {2017-04-19 19:20:49 +0000}, Doi = {10.1016/j.neuron.2014.04.029}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Brain-Derived Neurotrophic Factor; Calcium; Cells, Cultured; Female; Glutamic Acid; JNK Mitogen-Activated Protein Kinases; Neurons; Phosphorylation; Proto-Oncogene Proteins c-jun; Signal Transduction; Spinal Cord; Xenopus laevis; gamma-Aminobutyric Acid}, Month = {Jun}, Number = {5}, Pages = {1004-16}, Pmc = {PMC4072120}, pmid = {24908484}, Pst = {ppublish}, Title = {Non-cell-autonomous mechanism of activity-dependent neurotransmitter switching}, Volume = {82}, Year = {2014}, url = {papers/Guemez-Gamboa_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.04.029}} @article{Devor:2013, Abstract = {The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has focused scientific attention on the necessary tools to understand the human brain and mind. Here, we outline our collective vision for what we can achieve within a decade with properly targeted efforts and discuss likely technological deliverables and neuroscience progress.}, Author = {Devor, Anna and Bandettini, Peter A and Boas, David A and Bower, James M and Buxton, Richard B and Cohen, Lawrence B and Dale, Anders M and Einevoll, Gaute T and Fox, Peter T and Franceschini, Maria Angela and Friston, Karl J and Fujimoto, James G and Geyer, Mark A and Greenberg, Joel H and Halgren, Eric and H{\"a}m{\"a}l{\"a}inen, Matti S and Helmchen, Fritjof and Hyman, Bradley T and Jasanoff, Alan and Jernigan, Terry L and Judd, Lewis L and Kim, Seong-Gi and Kleinfeld, David and Kopell, Nancy J and Kutas, Marta and Kwong, Kenneth K and Larkum, Matthew E and Lo, Eng H and Magistretti, Pierre J and Mandeville, Joseph B and Masliah, Eliezer and Mitra, Partha P and Mobley, William C and Moskowitz, Michael A and Nimmerjahn, Axel and Reynolds, John H and Rosen, Bruce R and Salzberg, Brian M and Schaffer, Chris B and Silva, Gabriel A and So, Peter T C and Spitzer, Nicholas C and Tootell, Roger B and Van Essen, David C and Vanduffel, Wim and Vinogradov, Sergei A and Wald, Lawrence L and Wang, Lihong V and Weber, Bruno and Yodh, Arjun G}, Date-Added = {2017-04-19 19:20:48 +0000}, Date-Modified = {2017-04-19 19:20:48 +0000}, Doi = {10.1016/j.neuron.2013.09.008}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Biomedical Research; Brain Mapping; Humans; Neurosciences}, Month = {Oct}, Number = {2}, Pages = {270-4}, Pmc = {PMC3864648}, pmid = {24139032}, Pst = {ppublish}, Title = {The challenge of connecting the dots in the B.R.A.I.N}, Volume = {80}, Year = {2013}, url = {papers/Devor_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.09.008}} @article{Demarque:2010, Abstract = {Genetic programs, environmental factors, and electrical activity interact to drive the maturation of the brain. Although the cascade of transcription factors that leads to specification of the serotonergic phenotype has been well characterized, its interactions with electrical activity are not known. Here we show that spontaneous calcium spike activity in the hindbrain of developing Xenopus laevis larvae modulates the specification of serotonergic neurons via regulation of expression of the Lmx1b transcription factor. Activity acts downstream of Nkx2.2 but upstream of Lmx1b, leading to regulation of the serotonergic phenotype. Using global manipulation of activity and targeted alteration of Lmx1b expression, we also demonstrate that changes in the number of serotonergic neurons change larval swimming behavior. The results link activity-dependent regulation of a transcription factor to transmitter specification and altered behavior.}, Author = {Demarque, Micha{\"e}l and Spitzer, Nicholas C}, Date-Added = {2017-04-19 19:20:45 +0000}, Date-Modified = {2017-04-19 19:20:45 +0000}, Doi = {10.1016/j.neuron.2010.06.006}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Action Potentials; Animals; Behavior, Animal; Bromodeoxyuridine; Calcium; Electroporation; Embryo, Nonmammalian; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Homeodomain Proteins; Membrane Potentials; Neurons; Otx Transcription Factors; Potassium Channels, Inwardly Rectifying; RNA, Messenger; Raphe Nuclei; Serotonin; Sodium Channels; Statistics, Nonparametric; Swimming; Transcription Factors; Tryptophan Hydroxylase; Xenopus Proteins; Xenopus laevis; gamma-Aminobutyric Acid}, Month = {Jul}, Number = {2}, Pages = {321-34}, Pmc = {PMC2913149}, pmid = {20670838}, Pst = {ppublish}, Title = {Activity-dependent expression of Lmx1b regulates specification of serotonergic neurons modulating swimming behavior}, Volume = {67}, Year = {2010}, url = {papers/Demarque_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.06.006}} @article{Desarmenien:1991, Abstract = {The delayed rectifier current of embryonic Xenopus spinal neurons plays the central role in developmental conversion of calcium-dependent action potentials to sodium-dependent spikes. During its maturation, this potassium current undergoes a pronounced increase in rate of activation. The mechanism underlying the change in kinetics was analyzed with whole-cell voltage clamp of neurons cultured under various conditions. Calcium is necessary at an early stage of development, to permit influx that triggers subsequent release of calcium from intracellular stores. Its action is prevented by depletion of protein kinase C and mimicked by stimulation of the kinase. Calcium influx through voltage-dependent channels at early stages of development regulates the differentiation of potassium current kinetics and modulation of the ionic dependence of action potentials.}, Author = {Desarmenien, M G and Spitzer, N C}, Date-Added = {2017-04-19 19:20:43 +0000}, Date-Modified = {2017-04-19 19:20:43 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Calcium; Cell Aging; Chlorides; Electric Conductivity; Neurons; Potassium; Protein Kinase C; Sodium; Spinal Cord; Xenopus}, Month = {Nov}, Number = {5}, Pages = {797-805}, pmid = {1742026}, Pst = {ppublish}, Title = {Role of calcium and protein kinase C in development of the delayed rectifier potassium current in Xenopus spinal neurons}, Volume = {7}, Year = {1991}} @article{Pattabiraman:2014, Abstract = {Elucidating the genetic control of cerebral cortical (pallial) development is essential for understanding function, evolution, and disorders of the brain. Transcription factors (TFs) that embryonically regulate pallial regionalization are expressed in gradients, raising the question of how discrete domains are generated. We provide evidence that small enhancer elements active in protodomains integrate broad transcriptional information. CreER(T2) and GFP expression from 14 different enhancer elements in stable transgenic mice allowed us to define a comprehensive regional fate map of the pallium. We explored transcriptional mechanisms that control the activity of the enhancers using informatics, in vivo occupancy by TFs that regulate cortical patterning (CoupTFI, Pax6, and Pbx1), and analysis of enhancer activity in Pax6 mutants. Overall, the results provide insights into how broadly expressed patterning TFs regulate the activity of small enhancer elements that drive gene expression in pallial protodomains that fate map to distinct cortical regions.}, Author = {Pattabiraman, Kartik and Golonzhka, Olga and Lindtner, Susan and Nord, Alex S and Taher, Leila and Hoch, Renee and Silberberg, Shanni N and Zhang, Dongji and Chen, Bin and Zeng, HongKui and Pennacchio, Len A and Puelles, Luis and Visel, Axel and Rubenstein, John L R}, Date-Added = {2017-04-19 19:16:56 +0000}, Date-Modified = {2017-04-19 19:16:56 +0000}, Doi = {10.1016/j.neuron.2014.04.014}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Binding Sites; COUP Transcription Factor I; Cerebral Cortex; Enhancer Elements, Genetic; Eye Proteins; Gene Expression Regulation, Developmental; Hippocampus; Homeodomain Proteins; Humans; Mice; Mice, Transgenic; PAX6 Transcription Factor; Paired Box Transcription Factors; Repressor Proteins; Transcription Factors; Transcription, Genetic}, Month = {Jun}, Number = {5}, Pages = {989-1003}, Pmc = {PMC4104757}, pmid = {24814534}, Pst = {ppublish}, Title = {Transcriptional regulation of enhancers active in protodomains of the developing cerebral cortex}, Volume = {82}, Year = {2014}, url = {papers/Pattabiraman_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.04.014}} @article{Eckler:2015, Abstract = {We recently published genetic lineage-tracing experiments using the Fezf2 and Cux2 loci. These experiments demonstrated that at both the clonal and population levels Fezf2(+) RGCs are multipotent and that at the population level Cux2(+) RGCs are multipotent. Here, we extend our work on the lineages of Fezf2(+) and Cux2(+) RGCs. Clonal analysis of E10.5 neocortical progenitors suggests that most, if not all, Cux2(+) and Fezf2(+) RGCs generate diverse projection neuron subtypes located throughout layers 2-6. These results support our previous conclusion that both Fezf2(+) and Cux2(+) RGCs are multipotent neocortical progenitors. This Matters Arising Response paper addresses the Gil-Sanz et al. (2015) Matters Arising paper, published concurrently in Neuron.}, Author = {Eckler, Matthew J and Nguyen, Ton D and McKenna, William L and Fastow, Ben L and Guo, Chao and Rubenstein, John L R and Chen, Bin}, Date-Added = {2017-04-19 19:16:13 +0000}, Date-Modified = {2017-04-19 19:16:13 +0000}, Doi = {10.1016/j.neuron.2015.04.020}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Cell Lineage; Gene Expression Regulation, Developmental; Homeodomain Proteins; Multipotent Stem Cells; Neocortex; Nerve Tissue Proteins; Neurogenesis; Neurons; Oligodendroglia}, Month = {May}, Number = {4}, Pages = {1100-8}, Pmc = {PMC4441766}, pmid = {25996137}, Pst = {ppublish}, Title = {Cux2-positive radial glial cells generate diverse subtypes of neocortical projection neurons and macroglia}, Volume = {86}, Year = {2015}, url = {papers/Eckler_Neuron2015.pdf}, Bdsk-File-2 = {papers/Eckler_Neuron2015a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.04.020}} @article{Thompson:2009, Abstract = {The effects of prenatal exposure to drugs on brain development are complex and are modulated by the timing, dose and route of drug exposure. It is difficult to assess these effects in clinical cohorts as these are beset with problems such as multiple exposures and difficulties in documenting use patterns. This can lead to misinterpretation of research findings by the general public, the media and policy makers, who may mistakenly assume that the legal status of a drug correlates with its biological impact on fetal brain development and long-term clinical outcomes. It is important to close the gap between what science tells us about the impact of prenatal drug exposure on the fetus and the mother and what we do programmatically with regard to at-risk populations.}, Author = {Thompson, Barbara L and Levitt, Pat and Stanwood, Gregg D}, Date-Added = {2017-04-19 18:27:12 +0000}, Date-Modified = {2017-04-19 18:27:12 +0000}, Doi = {10.1038/nrn2598}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Alcohols; Amphetamine; Antidepressive Agents; Brain; Child; Crack Cocaine; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Maternal-Fetal Exchange; Methamphetamine; Nicotine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Substance-Related Disorders}, Month = {Apr}, Number = {4}, Pages = {303-12}, Pmc = {PMC2777887}, pmid = {19277053}, Pst = {ppublish}, Title = {Prenatal exposure to drugs: effects on brain development and implications for policy and education}, Volume = {10}, Year = {2009}, url = {papers/Thompson_NatRevNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2598}} @article{Holmes:2001, Abstract = {BACKGROUND: The frequency of major malformations, growth retardation, and hypoplasia of the midface and fingers, known as the anticonvulsant embryopathy, is increased in infants exposed to anticonvulsant drugs in utero. However, whether the abnormalities are caused by the maternal epilepsy itself or by exposure to anticonvulsant drugs is not known. METHODS: We screened 128,049 pregnant women at delivery to identify three groups of infants: those exposed to anticonvulsant drugs, those unexposed to anticonvulsant drugs but with a maternal history of seizures, and those unexposed to anticonvulsant drugs with no maternal history of seizures (control group). The infants were examined systematically for the presence of major malformations, signs of hypoplasia of the midface and fingers, microcephaly, and small body size. RESULTS: The combined frequency of anticonvulsant embryopathy was higher in 223 infants exposed to one anticonvulsant drug than in 508 control infants (20.6 percent vs. 8.5 percent; odds ratio, 2.8; 95 percent confidence interval, 1.1 to 9.7). The frequency was also higher in 93 infants exposed to two or more anticonvulsant drugs than in the controls (28.0 percent vs. 8.5 percent; odds ratio, 4.2; 95 percent confidence interval, 1.1 to 5.1). The 98 infants whose mothers had a history of epilepsy but took no anticonvulsant drugs during the pregnancy did not have a higher frequency of those abnormalities than the control infants. CONCLUSIONS: A distinctive pattern of physical abnormalities in infants of mothers with epilepsy is associated with the use of anticonvulsant drugs during pregnancy, rather than with epilepsy itself.}, Author = {Holmes, L B and Harvey, E A and Coull, B A and Huntington, K B and Khoshbin, S and Hayes, A M and Ryan, L M}, Date-Added = {2017-04-19 18:26:24 +0000}, Date-Modified = {2017-04-19 18:26:24 +0000}, Doi = {10.1056/NEJM200104123441504}, Journal = {N Engl J Med}, Journal-Full = {The New England journal of medicine}, Mesh = {Abnormalities, Drug-Induced; Anticonvulsants; Carbamazepine; Case-Control Studies; Congenital Abnormalities; Epilepsy; Face; Female; Fetal Growth Retardation; Fingers; Humans; Infant, Newborn; Logistic Models; Phenobarbital; Phenytoin; Pregnancy; Pregnancy Complications; Valproic Acid}, Month = {Apr}, Number = {15}, Pages = {1132-8}, pmid = {11297704}, Pst = {ppublish}, Title = {The teratogenicity of anticonvulsant drugs}, Volume = {344}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1056/NEJM200104123441504}} @article{Manent:2007, Abstract = {PURPOSE: The management of epilepsy during pregnancy entails a number of concerns. While seizures may affect adversely maternal and fetal outcome, antiepileptic drugs (AEDs) may increase the incidence of congenital abnormalities and possibly affect postnatal cognitive development in the offspring. Experimental animal studies can aid in assessing teratogenic features associated with individual AEDs and/or with seizures, and to identify the mechanisms involved. The purpose of this study was to investigate the consequences of prenatal exposure to (a) different AEDs and (b) maternal seizures on brain maturational processes in rats. METHODS: Pregnant rats received from embryonic days 14 to 19 intraperitoneal injections of carbamazepine (20 mg/kg/day), vigabatrin (200 mgkg/day), and valproate (100 mg/kg/day) at doses not widely different from those used clinically. Pups exposed to AEDs in utero were analyzed postnatally. Animals born to "kindled" pregnant animals that had experienced one generalized convulsive seizure per day during the same gestational period were analyzed in parallel. RESULTS: Prenatal exposure to vigabatrin and valproate, which act on GABA signaling, induced hippocampal and cortical dysplasias, which were likely to result from a neuronal migration defect and neuronal death. By contrast, offspring of rats exposed to carbamazepine (which at the dose used produced low plasma concentrations) or to generalized convulsive seizures showed no clear-cut evidence of dysplasias. CONCLUSIONS: We suggest that AEDs that increase the extracellular concentration of GABA might induce severe neuronal migration disorders. Drugs acting through other molecular targets would also perturb cortical maturation. The potential clinical relevance of these results should be a subject of future research.}, Author = {Manent, Jean-Bernard and Jorquera, Isabel and Mazzucchelli, Iolanda and Depaulis, Antoine and Perucca, Emilio and Ben-Ari, Yehezkel and Represa, Alfonso}, Date-Added = {2017-04-19 18:22:58 +0000}, Date-Modified = {2017-04-19 18:22:58 +0000}, Doi = {10.1111/j.1528-1167.2007.01056.x}, Journal = {Epilepsia}, Journal-Full = {Epilepsia}, Mesh = {Abnormalities, Drug-Induced; Animals; Anticonvulsants; Carbamazepine; Cerebral Cortex; Female; Fetus; GABA Agents; Hippocampus; Kindling, Neurologic; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Rats; Seizures; Valproic Acid; Vigabatrin; gamma-Aminobutyric Acid}, Month = {Apr}, Number = {4}, Pages = {684-93}, pmid = {17437411}, Pst = {ppublish}, Title = {Fetal exposure to GABA-acting antiepileptic drugs generates hippocampal and cortical dysplasias}, Volume = {48}, Year = {2007}, url = {papers/Manent_Epilepsia2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1528-1167.2007.01056.x}} @article{Ballesteros-Yanez:2010, Abstract = {The neuronal nicotinic acetylcholine receptors (nAChRs) are allosteric membrane proteins involved in multiple cognitive processes, including attention, learning, and memory. The most abundant form of heterooligomeric nAChRs in the brain contains the beta2- and alpha4- subunits and binds nicotinic agonists with high affinity. In the present study, we investigated in the mouse the consequences of the deletion of one of the nAChR components: the beta2-subunit (beta2(-/-)) on the microanatomy of cortical pyramidal cells. Using an intracellular injection method, complete basal dendritic arbors of 650 layer III pyramidal neurons were sampled from seven cortical fields, including primary sensory, motor, and associational areas, in both beta2(-/-) and WT animals. We observed that the pyramidal cell phenotype shows significant quantitative differences among different cortical areas in mutant and WT mice. In WT mice, the density of dendritic spines was rather similar in all cortical fields, except in the prelimbic/infralimbic cortex, where it was significantly higher. In the absence of the beta2-subunit, the most significant reduction in the density of spines took place in this high-order associational field. Our data suggest that the beta2-subunit is involved in the dendritic morphogenesis of pyramidal neurons and, in particular, in the circuits that contribute to the high-order functional connectivity of the cerebral cortex.}, Author = {Ballesteros-Y{\'a}{\~n}ez, Inmaculada and Benavides-Piccione, Ruth and Bourgeois, Jean-Pierre and Changeux, Jean-Pierre and DeFelipe, Javier}, Date-Added = {2017-04-18 20:27:46 +0000}, Date-Modified = {2017-04-18 20:27:46 +0000}, Doi = {10.1073/pnas.1006269107}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Cerebral Cortex; Dendrites; Dendritic Cells; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Mutation; Neurons; Phenotype; Pyramidal Cells; Receptors, Nicotinic}, Month = {Jun}, Number = {25}, Pages = {11567-72}, Pmc = {PMC2895077}, pmid = {20534523}, Pst = {ppublish}, Title = {Alterations of cortical pyramidal neurons in mice lacking high-affinity nicotinic receptors}, Volume = {107}, Year = {2010}, url = {papers/Ballesteros-Yáñez_ProcNatlAcadSciUSA2010.pdf}} @article{Ichinohe:2012, Abstract = {Structures associated with the small-scale module called "minicolumn" can be observed frequently in the cerebral cortex. However, the description of functional characteristics remains obscure. A significant confounding factor is the marked variability both in the definition of a minicolumn and in the diagnostic markers for identifying a minicolumn (see for review, Jones, 2000; DeFelipe et al., 2002; Rockland and Ichinohe, 2004). Within a minicolumn, cell columns are easily visualized by conventional Nissl staining. Dendritic bundles were first discovered with Golgi methods, but are more easily seen with microtubule-associated protein 2 immunohistochemistry. Myelinated axon bundles can be seen by Tau immunohistochemistry or myelin staining. Axon bundles of double bouquet cell can be seen by calbindin immunohistochemistry. The spatial interrelationship among these morphological elements is more complex than expected and is neither clear nor unanimously agreed upon. In this review, I would like to focus first on the minicolumnar structure found in layers 1 and 2 of the rat granular retrosplenial cortex. This modular structure was first discovered as a combination of prominent apical dendritic bundles from layer 2 pyramidal neurons and spatially matched thalamocortical patchy inputs (Wyss et al., 1990). Further examination showed more intricate components of this modular structure, which will be reviewed in this paper. Second, the postnatal development of this structure and potential molecular players for its formation will be reviewed. Thirdly, I will discuss how this modular organization is transformed in mutant rodents with a disorganized layer structure in the cerebral cortex (i.e., reeler mouse and shaking rat Kawasaki). Lastly, the potential significance of this type of module will be discussed.}, Author = {Ichinohe, Noritaka}, Date-Added = {2017-04-18 20:17:18 +0000}, Date-Modified = {2017-04-18 20:17:18 +0000}, Doi = {10.3389/fnana.2011.00069}, Journal = {Front Neuroanat}, Journal-Full = {Frontiers in neuroanatomy}, Keywords = {cortical modular organization; corticocortical; dendritic bundle; input and recipient matching; thalamocortical}, Pages = {69}, Pmc = {PMC3254062}, pmid = {22275884}, Pst = {epublish}, Title = {Small-scale module of the rat granular retrosplenial cortex: an example of the minicolumn-like structure of the cerebral cortex}, Volume = {5}, Year = {2012}, url = {papers/Ichinohe_FrontNeuroanat2012.pdf}} @article{Murakami2015, Abstract = {Due to recent advances of genetic manipulation, mouse brain has become a useful model for studying brain function, which demands whole brain functional mapping techniques in the mouse brain. In the present study, to finely map visual responsive areas in the mouse brain, we combined high-resolution wide-field optical imaging with transgenic mice containing the genetically encoded Ca(2+) indicator, GCaMP3. With the high signal amplitude of GCaMP3 expressing in excitatory neurons, this system allowed neural activity to be observed with relatively fine spatial resolution and cell-type specificity. To evaluate this system, we examined whether non-visual areas exhibited a visual response over the entire surface of the mouse hemisphere. We found that two association areas, the retrosplenial area (RS) and secondary motor/anterior cingulate area (M2/AC), were significantly responsive to drifting gratings. Examination using gratings with distinct spatiotemporal frequency parameters revealed that the RS strongly responded to high-spatial and low-temporal frequency gratings. The M2/AC exhibited a response property similar to that of the RS, though it was not statistically significant. Finally, we performed cellular imaging using two-photon microscopy to examine orientation and direction selectivity of individual neurons, and found that a minority of neurons in the RS clearly showed visual responses sharply selective for orientation and direction. These results suggest that neurons in RS encode visual information of fine spatial details in images. Thus, the present study shows the usefulness of the functional mapping method using a combination of wide-field and two-photon Ca(2+) imaging, which allows for whole brain mapping with high spatiotemporal resolution and cell-type specificity.}, Author = {Murakami, Tomonari and Yoshida, Takashi and Matsui, Teppei and Ohki, Kenichi}, Date-Added = {2017-04-18 20:16:45 +0000}, Date-Modified = {2017-04-18 20:16:45 +0000}, Doi = {10.3389/fnmol.2015.00020}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {GCaMP3; retrosplenial area; transgenic mouse; visual response; wide-field Ca2+ imaging}, Pages = {20}, Pmc = {PMC4458613}, pmid = {26106292}, Pst = {epublish}, Title = {Wide-field Ca(2+) imaging reveals visually evoked activity in the retrosplenial area}, Volume = {8}, Year = {2015}, url = {papers/Murakami_FrontMolNeurosci2015.pdf}} @article{Donoghue:1988, Abstract = {Somatotopic representation patterns in the motor cortex (MI) of rats that had a unilateral forelimb amputation on the first postnatal day were examined after 2-4 months of survival. Intracortical electrical stimulation and recording techniques were used to map the somatic representation in MI and in the somatic sensory cortex (SI). In normal rats, vibrissa, forelimb, and hindlimb areas comprise the bulk of the MI representation. Stimulation within the forelimb area elicits elbow, wrist, or digit movements at the lowest current intensities. The proximal limb representation appears to be contained within the distal forelimb area, since shoulder movements are nearly always evoked by stimulating at higher current intensities at some distal forelimb sites. In agreement with previous studies, the distal forelimb representation overlapped the adjacent part of the granular SI cortex. Following removal of the forelimb at birth, 3 novel features of MI organization were observed. First, the areas from which stimulation evoked movements of the vibrissa or the shoulder musculature were larger than normal. Stimulation thresholds were lower than those required for comparable movements in normal rats throughout these areas, suggesting that nerve section had not simply unmasked a high-threshold representation. Second, vibrissa movements were more commonly paired with movements of the proximal forelimb muscles at the same site. Third, stimulation in the adjacent granular SI cortex failed to evoke shoulder or trunk movements, although receptive-field mapping in this region showed that cells were responsive to cutaneous stimulation of the trunk and shoulder region. These results indicate that several organizational features develop differently in MI following perinatal nerve injury: certain remaining muscle groups have enlarged cortical representations, there is a strengthening of some normally weak connections from MI to the proximal musculature, and muscles are grouped in unusual combinations. These data demonstrate that the formation of MI representation patterns is strongly influenced by nerve injury during the perinatal period.}, Author = {Donoghue, J P and Sanes, J N}, Date-Added = {2017-04-18 19:58:46 +0000}, Date-Modified = {2017-04-18 19:58:46 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Amputation; Animals; Animals, Newborn; Brain Mapping; Denervation; Differential Threshold; Female; Forelimb; Motor Cortex; Movement; Rats; Rats, Inbred Strains; Reference Values; Somatosensory Cortex; Vibrissae}, Month = {Sep}, Number = {9}, Pages = {3221-32}, pmid = {3171676}, Pst = {ppublish}, Title = {Organization of adult motor cortex representation patterns following neonatal forelimb nerve injury in rats}, Volume = {8}, Year = {1988}, url = {papers/Donoghue_JNeurosci1988.pdf}} @article{Tennant:2011, Abstract = {The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations. It included a large caudal forelimb area, dominated by digit representation, and a small rostral forelimb area, containing elbow and wrist representations. When the entire motor cortex was mapped, the forelimb was found to be the largest movement representation, followed by head and hindlimb representations. The ICMS-defined motor cortex spanned cytoarchitecturally identified lateral agranular cortex (AGl) and also extended into medial agranular cortex. Forelimb and hindlimb representations extended into granular cortex in a region that also had cytoarchitectural characteristics of AGl, consistent with the primary motor-somatosensory overlap zone (OL) characterized in rats. Thus, the mouse motor cortex has homologies with the rat in having 2 forelimb representations and an OL but is distinct in the predominance of digit representations.}, Author = {Tennant, Kelly A and Adkins, Deanna L and Donlan, Nicole A and Asay, Aaron L and Thomas, Nagheme and Kleim, Jeffrey A and Jones, Theresa A}, Date-Added = {2017-04-18 19:20:36 +0000}, Date-Modified = {2017-04-18 19:20:36 +0000}, Doi = {10.1093/cercor/bhq159}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Brain Mapping; Electric Stimulation; Forelimb; Male; Mice; Mice, Inbred C57BL; Motor Cortex}, Month = {Apr}, Number = {4}, Pages = {865-76}, Pmc = {PMC3059888}, pmid = {20739477}, Pst = {ppublish}, Title = {The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture}, Volume = {21}, Year = {2011}, url = {papers/Tennant_CerebCortex2011.pdf}} @article{Belanger:2011, Abstract = {The energy requirements of the brain are very high, and tight regulatory mechanisms operate to ensure adequate spatial and temporal delivery of energy substrates in register with neuronal activity. Astrocytes-a type of glial cell-have emerged as active players in brain energy delivery, production, utilization, and storage. Our understanding of neuroenergetics is rapidly evolving from a "neurocentric" view to a more integrated picture involving an intense cooperativity between astrocytes and neurons. This review focuses on the cellular aspects of brain energy metabolism, with a particular emphasis on the metabolic interactions between neurons and astrocytes.}, Author = {B{\'e}langer, Mireille and Allaman, Igor and Magistretti, Pierre J}, Date-Added = {2017-04-17 23:16:55 +0000}, Date-Modified = {2017-04-17 23:16:55 +0000}, Doi = {10.1016/j.cmet.2011.08.016}, Journal = {Cell Metab}, Journal-Full = {Cell metabolism}, Mesh = {Astrocytes; Brain; Energy Metabolism; Glycogen; Lactic Acid; Models, Biological; Neurons; Oxidative Stress; Regional Blood Flow}, Month = {Dec}, Number = {6}, Pages = {724-38}, pmid = {22152301}, Pst = {ppublish}, Title = {Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation}, Volume = {14}, Year = {2011}, url = {papers/Belanger_CellMetab2011.pdf}} @article{Raichle:2002, Author = {Raichle, Marcus E and Gusnard, Debra A}, Date-Added = {2017-04-17 17:36:54 +0000}, Date-Modified = {2017-04-17 17:36:54 +0000}, Doi = {10.1073/pnas.172399499}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Brain; Energy Metabolism; Humans}, Month = {Aug}, Number = {16}, Pages = {10237-9}, Pmc = {PMC124895}, pmid = {12149485}, Pst = {ppublish}, Title = {Appraising the brain's energy budget}, Volume = {99}, Year = {2002}, url = {papers/Raichle_ProcNatlAcadSciUSA2002.pdf}} @article{Parkes:2001, Abstract = {A shape can be more difficult to identify when other shapes are near it. For example, when several grating patches are viewed parafoveally, observers are unable to report the orientation of the central patch. This phenomenon, known as 'crowding,' has historically been confused with lateral masking, in which one stimulus attenuates signals generated by another stimulus. Here we show that despite their inability to report the orientation of an individual patch, observers can reliably estimate the average orientation, demonstrating that the local orientation signals are combined rather than lost. Our results imply that crowding is distinct from ordinary masking, and is perhaps related to texture perception. Under crowded conditions, the orientation signals in primary visual cortex are pooled before they reach consciousness.}, Author = {Parkes, L and Lund, J and Angelucci, A and Solomon, J A and Morgan, M}, Date-Added = {2017-04-12 17:55:10 +0000}, Date-Modified = {2017-04-12 17:55:10 +0000}, Doi = {10.1038/89532}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Algorithms; Form Perception; Humans; Models, Biological; Visual Fields}, Month = {Jul}, Number = {7}, Pages = {739-44}, pmid = {11426231}, Pst = {ppublish}, Title = {Compulsory averaging of crowded orientation signals in human vision}, Volume = {4}, Year = {2001}, url = {papers/Parkes_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/89532}} @article{King:1993, Abstract = {Neglect in human and non-human primates has been demonstrated following unilateral lesions of both posterior parietal and prefrontal areas. While it has now been well established that a unilateral lesion of the rodent analog of dorsolateral prefrontal cortex, medial agranular cortex (AGm), results in neglect, the effects of unilateral damage restricted to rodent posterior parietal cortex (PPC) have not been examined in detail. The current study assessed rats with unilateral lesions of PPC or AGm on their ability to orient to unilateral and bilateral stimulation. Since it has been proposed in both the primate and rodent literatures that frontal areas may be responsible for the perception of near space while parietal areas may be responsible for far space, stimuli were presented at two different distances. Lesions of PPC and AGm resulted in severe neglect relative to control operates, with both PPC and AGm operates manifesting severe hemi-inattention and allesthesia relative to control operates. After behavioral recovery from neglect there was no evidence of extinction to bilateral simultaneous stimulation. While neglect to visual stimuli predominated in unilateral PPC operates, unilateral AGm operates had severe neglect in all modalities. In addition, while both left and right PPC operates showed contralesional neglect, AGm operates demonstrated the lateralized differences in neglect reported in previous studies. All groups demonstrated an approximately equivalent level of neglect to stimuli presented at the two different distances, and thus failed to support the suggestion of a peripersonal-extrapersonal dichotomy between frontal and parietal areas in rodents.}, Author = {King, V R and Corwin, J V}, Date-Added = {2017-04-08 00:47:52 +0000}, Date-Modified = {2017-04-08 00:47:52 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Mesh = {Animals; Attention; Brain Mapping; Distance Perception; Dominance, Cerebral; Extinction, Psychological; Food Deprivation; Male; Motivation; Neural Pathways; Orientation; Parietal Lobe; Prefrontal Cortex; Rats; Sound Localization; Touch}, Month = {Apr}, Number = {2}, Pages = {117-31}, pmid = {8323710}, Pst = {ppublish}, Title = {Comparisons of hemi-inattention produced by unilateral lesions of the posterior parietal cortex or medial agranular prefrontal cortex in rats: neglect, extinction, and the role of stimulus distance}, Volume = {54}, Year = {1993}, url = {papers/King_BehavBrainRes1993.pdf}} @article{Kesner:1989, Abstract = {Animals with medial prefrontal cortex or parietal cortex lesions and sham-operated and non-operated controls were tested for the acquisition of an adjacent arm task that accentuated the importance of egocentric spatial localization and a cheese board task that accentuated the importance of allocentric spatial localization. Results indicated that relative to controls, animals with medial-prefrontal cortex lesions are impaired on the adjacent arm task but displayed facilitation on the cheese board task. In contrast, relative to controls, rats with parietal cortex lesions are impaired on the cheese board task but show no impairment on the adjacent arm task. The data suggest a double dissociation of function between medial prefrontal cortex and parietal cortex in terms of coding of egocentric versus allocentric spatial information.}, Author = {Kesner, R P and Farnsworth, G and DiMattia, B V}, Date-Added = {2017-04-08 00:45:29 +0000}, Date-Modified = {2017-04-08 00:45:29 +0000}, Journal = {Behav Neurosci}, Journal-Full = {Behavioral neuroscience}, Mesh = {Animals; Appetitive Behavior; Attention; Brain Mapping; Discrimination Learning; Frontal Lobe; Male; Memory; Mental Recall; Orientation; Parietal Lobe; Rats; Rats, Inbred Strains; Reaction Time; Retention (Psychology)}, Month = {Oct}, Number = {5}, Pages = {956-61}, pmid = {2803562}, Pst = {ppublish}, Title = {Double dissociation of egocentric and allocentric space following medial prefrontal and parietal cortex lesions in the rat}, Volume = {103}, Year = {1989}} @article{King:1992, Abstract = {Studies of spatial behavior in both the human and non-human primate have generally focused on the role of the posterior parietal and prefrontal cortices and have indicated that destruction of these regions produce allocentric and egocentric deficits, respectively. The present study examined the role of the rodent analogs of these regions, the posterior parietal (PPC) and medial agranular (AGm) cortices, in egocentric and allocentric spatial processing, and whether spatial processing in rodents is organized in a hemispatial and/or lateralized manner as has been found in the primate. Eighty male rats receiving either a unilateral or bilateral lesion of AGm or PPC were examined on an egocentric (adjacent arm) or an allocentric (cheeseboard) maze task. The results indicated that PPC and AGm have dissociable spatial functions. Bilateral AGm destruction resulted in egocentric spatial deficits, and unilateral AGm operates demonstrated an intermediate deficit. In contrast, bilateral PPC operates demonstrated a severe deficit in allocentric processing. In addition, there were lateralized differences in the performance of unilateral PPC operates. While right PPC lesions resulted in a significant deficit on the allocentric task, no such deficit was seen in left PPC operates. In addition, neither unilateral AGm nor unilateral PPC operates demonstrated a hemispatial impairment on either the egocentric or allocentric tasks.}, Author = {King, V R and Corwin, J V}, Date-Added = {2017-04-08 00:42:49 +0000}, Date-Modified = {2017-04-08 00:42:49 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Mesh = {Animals; Brain Mapping; Dominance, Cerebral; Hippocampus; Male; Mental Recall; Motivation; Neural Pathways; Neurons; Orientation; Parietal Lobe; Prefrontal Cortex; Rats; Retention (Psychology); Social Environment}, Month = {Sep}, Number = {1-2}, Pages = {53-68}, pmid = {1449649}, Pst = {ppublish}, Title = {Spatial deficits and hemispheric asymmetries in the rat following unilateral and bilateral lesions of posterior parietal or medial agranular cortex}, Volume = {50}, Year = {1992}, url = {papers/King_BehavBrainRes1992.pdf}} @article{Dawson:1986, Abstract = {Unilateral lesions in such brain regions as medial frontal cortex and superior colliculus produce polysensory neglect contralateral to the lesion. Since the pineal gland is an unpaired brain structure, both electrophysiologically and hormonally responsive to visual and auditory stimulation, it may modulate bilateral sensory attention mechanisms. Long-Evans male rats were given pineal or sham lesions and were tested behaviourally. Sensory assessment revealed that in comparison to sham animals rats with pineal lesion exhibited unilateral visual and auditory neglect to stimuli presented on either side of the body. Animals with pineal lesions were more likely than sham-lesioned animals to demonstrate visual allesthesis and, compared to sham-lesioned rats, showed extinction on the left side to bilateral simultaneous visual stimulation. This is the first report that midline neuroendocrine damage can produce bilateral sensory inattention.}, Author = {Dawson, K A and Crowne, D P and Richardson, C M}, Date-Added = {2017-04-08 00:39:53 +0000}, Date-Modified = {2017-04-08 00:39:53 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Mesh = {Animals; Attention; Auditory Perception; Brain Mapping; Male; Orientation; Pineal Gland; Rats; Reflex; Visual Fields; Visual Perception}, Month = {Feb}, Number = {2}, Pages = {187-90}, pmid = {3964408}, Pst = {ppublish}, Title = {Pineal lesion produces bilateral visual and auditory inattention in the rat}, Volume = {19}, Year = {1986}} @article{Crowne:1986, Abstract = {Rats were given unilateral aspiration lesions of parietal, medial frontal, or dorsolateral frontal (motor) cortex and then tested for visual, auditory and tactile neglect, and for circling. All medial frontal lesion animals showed contralateral neglect in each modality and circled ipsiversively. The parietal lesion rats initially displayed contralateral visual and auditory neglect as severe as that in the medial frontal group. Three weeks after the lesions, the parietal group had a smaller residual deficit on the visual test than the medial frontal group. In the first week, parietal animals responded less than the medial frontals to stroking the vibrissae but were more responsive to mild pinching of a toe contralateral to the lesion side. In striking contrast to the medial frontal animals, the parietal group circled strongly to the contralateral side. No rat with a motor cortex lesion neglected or circled preferentially. Like medial frontal cortex, unilateral parietal lesions also produce neglect and circling, but there are important features distinguishing unilateral lesion effects in these two regions.}, Author = {Crowne, D P and Richardson, C M and Dawson, K A}, Date-Added = {2017-04-08 00:39:51 +0000}, Date-Modified = {2017-04-08 00:39:51 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Mesh = {Acoustic Stimulation; Animals; Frontal Lobe; Male; Orientation; Parietal Lobe; Photic Stimulation; Physical Stimulation; Rats; Sensation; Stereotyped Behavior; Visual Fields}, Month = {Dec}, Number = {3}, Pages = {227-31}, pmid = {3790245}, Pst = {ppublish}, Title = {Parietal and frontal eye field neglect in the rat}, Volume = {22}, Year = {1986}, url = {papers/Crowne_BehavBrainRes1986.pdf}} @article{Reep:1994, Abstract = {Anatomical and functional findings support the contention that there is a distinct posterior parietal cortical area (PPC) in the rat, situated between the rostrally adjacent hindlimb sensorimotor area and the caudally adjacent secondary visual areas. The PPC is distinguished from these areas by receiving thalamic afferents from the lateral dorsal (LD), lateral posterior (LP), and posterior (Po) nuclei, in the absence of input from the ventrobasal complex (VB) or dorsal lateral geniculate (DLG) nuclei. Behavioral studies have demonstrated that PPC is involved in spatial orientation and directed attention. In the present study we used fluorescent retrograde axonal tracers primarily to investigate the cortical connections of PPC, in order to determine the organization of the circuitry by which PPC is likely to participate in these functions, and also to determine how the topography of its thalamic connections differs from that of neighboring cortical areas. The cortical connections of PPC involve the ventrolateral (VLO) and medial (MO) orbital areas, medial agranular cortex (area Fr2), portions of somatic sensory areas Par1 and Par2, secondary visual areas Oc2M and Oc2L, auditory area Te1, and retrosplenial cortex. The secondary visual areas Oc2L and Oc2M have cortical connections which are similar to those of PPC, but are restricted within orbital cortex to area VLO, and within area Fr2 to its caudal portion, and do not involve auditory area Te1. The cortical connections of hindlimb cortex are largely restricted to somatic sensory and motor areas. Retrosplenial cortex, which is medially adjacent to PPC, has cortical connections that are prominent with visual cortex, do not involve somatic sensory or auditory cortex, and include the presubiculum. We conclude that PPC is distinguished by its pattern of cortical connections with the somatic sensory, auditory and visual areas, and with areas Fr2, and VLO/MO, in addition to its exclusive thalamic connectivity with LD, LP and Po. Because recent behavioral studies indicate that PPC, Fr2 and VLO are involved in directed attention and spatial learning, we suggest that the interconnections among these three cortical areas represent a major component of the circuitry for these functions in rats.}, Author = {Reep, R L and Chandler, H C and King, V and Corwin, J V}, Date-Added = {2017-04-08 00:31:37 +0000}, Date-Modified = {2017-04-08 00:31:37 +0000}, Journal = {Exp Brain Res}, Journal-Full = {Experimental brain research}, Mesh = {Animals; Cerebral Cortex; Fluorescent Dyes; Hindlimb; Neural Pathways; Parietal Lobe; Rats; Somatosensory Cortex; Stereotaxic Techniques; Stilbamidines; Thalamus; Visual Cortex}, Number = {1}, Pages = {67-84}, pmid = {7813654}, Pst = {ppublish}, Title = {Rat posterior parietal cortex: topography of corticocortical and thalamic connections}, Volume = {100}, Year = {1994}, url = {papers/Reep_ExpBrainRes1994.pdf}} @article{Mountcastle:1975, Abstract = {Experiments were made on the posterior parietal association cortical areas 5 and in 17 hemispheres of 11 monkeys, 6 M. mulatta and 5 M. arctoides. The electrical signs of the activity of single cortical cells were recorded with microelectrodes in waking animals as they carried out certain behavioral acts in response to a series of sensory cues. The behavioral paradigms were one for detection alone, and a second for detection plus projection of the arm to contact a stationary or moving target placed at arm's length. Of the 125 microelectrode penetrations made, 1,451 neurons were identified in terms of the correlation of their activity with the behavioral acts and their sensitivity or lack of it to sensory stimuli delivered passively; 180 were studied quantitatively. The locations of cortical neurons were identified in serial sections; 94 penetrations and 1,058 neurons were located with certainty. About two-thirds of the neurons of area 5 were activated by passive rotation of the limbs at their joints; of these, 82% were related to single, contralateral joints, 10% to two or more contralateral joints, 6% to ipsilateral, and 2% to joints on both sides of the body. A few of the latter were active during complex bodily postures. A large proportion of area 5 neurons were relatively insensitive to passive joint rotations, as compared with similar neurons of the postcentral gyrus, but were driven to high rates of discharge when the same joint was rotated during an active movement of the animal...}, Author = {Mountcastle, V B and Lynch, J C and Georgopoulos, A and Sakata, H and Acuna, C}, Date-Added = {2017-04-07 18:13:36 +0000}, Date-Modified = {2017-04-07 18:13:36 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Mesh = {Animals; Brain Mapping; Exploratory Behavior; Eye Movements; Haplorhini; Joints; Macaca; Mechanoreceptors; Models, Neurological; Motor Skills; Neural Pathways; Neurons; Orientation; Parietal Lobe; Posture; Proprioception; Skin; Space Perception; Time Factors; Visual Perception}, Month = {Jul}, Number = {4}, Pages = {871-908}, pmid = {808592}, Pst = {ppublish}, Title = {Posterior parietal association cortex of the monkey: command functions for operations within extrapersonal space}, Volume = {38}, Year = {1975}, url = {papers/Mountcastle_JNeurophysiol1975.pdf}} @article{Andersen:1997, Abstract = {Recent experiments are reviewed that indicate that sensory signals from many modalities, as well as efference copy signals from motor structures, converge in the posterior parietal cortex in order to code the spatial locations of goals for movement. These signals are combined using a specific gain mechanism that enables the different coordinate frames of the various input signals to be combined into common, distributed spatial representations. These distributed representations can be used to convert the sensory locations of stimuli into the appropriate motor coordinates required for making directed movements. Within these spatial representations of the posterior parietal cortex are neural activities related to higher cognitive functions, including attention. We review recent studies showing that the encoding of intentions to make movements is also among the cognitive functions of this area.}, Author = {Andersen, R A and Snyder, L H and Bradley, D C and Xing, J}, Date-Added = {2017-04-07 18:07:19 +0000}, Date-Modified = {2017-04-07 18:07:19 +0000}, Doi = {10.1146/annurev.neuro.20.1.303}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Mesh = {Animals; Movement; Parietal Lobe; Space Perception}, Pages = {303-30}, pmid = {9056716}, Pst = {ppublish}, Title = {Multimodal representation of space in the posterior parietal cortex and its use in planning movements}, Volume = {20}, Year = {1997}, url = {papers/Andersen_AnnuRevNeurosci1997.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.20.1.303}} @article{Aziz-Zadeh:2006, Abstract = {A cortical network consisting of the inferior frontal, rostral inferior parietal, and posterior superior temporal cortices has been implicated in representing actions in the primate brain and is critical to imitation in humans. This neural circuitry may be an evolutionary precursor of neural systems associated with language. However, language is predominantly lateralized to the left hemisphere, whereas the degree of lateralization of the imitation circuitry in humans is unclear. We conducted a functional magnetic resonance imaging study of imitation of finger movements with lateralized stimuli and responses. During imitation, activity in the inferior frontal and rostral inferior parietal cortex, although fairly bilateral, was stronger in the hemisphere ipsilateral to the visual stimulus and response hand. This ipsilateral pattern is at variance with the typical contralateral activity of primary visual and motor areas. Reliably increased signal in the right superior temporal sulcus (STS) was observed for both left-sided and right-sided imitation tasks, although subthreshold activity was also observed in the left STS. Overall, the data indicate that visual and motor components of the human mirror system are not left-lateralized. The left hemisphere superiority for language, then, must be have been favored by other types of language precursors, perhaps auditory or multimodal action representations.}, Author = {Aziz-Zadeh, Lisa and Koski, Lisa and Zaidel, Eran and Mazziotta, John and Iacoboni, Marco}, Date-Added = {2017-04-05 01:54:49 +0000}, Date-Modified = {2017-04-05 01:54:49 +0000}, Doi = {10.1523/JNEUROSCI.2921-05.2006}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Adolescent; Adult; Brain Mapping; Dominance, Cerebral; Female; Fingers; Frontal Lobe; Humans; Imitative Behavior; Language; Male; Middle Aged; Movement; Nerve Net; Neurons; Parietal Lobe; Psychomotor Performance; Subtraction Technique; Temporal Lobe}, Month = {Mar}, Number = {11}, Pages = {2964-70}, pmid = {16540574}, Pst = {ppublish}, Title = {Lateralization of the human mirror neuron system}, Volume = {26}, Year = {2006}, url = {papers/Aziz-Zadeh_JNeurosci2006.pdf}} @article{Takano:2014, Abstract = {The mirror system in the brain is considered to be a neural basis of sociality, but previous studies have been limited to primates. Here we report an experimental task to examine the mirror system in rats. We show that a rat could reach to a pellet and grasp and eat it in front of another rat that was observing the reaching, which indicates that the task will enable us to start exploring the rat mirror system.}, Author = {Takano, Yuji and Ukezono, Masatoshi}, Date-Added = {2017-04-04 23:47:31 +0000}, Date-Modified = {2017-04-04 23:47:31 +0000}, Doi = {10.1038/srep06652}, Journal = {Sci Rep}, Journal-Full = {Scientific reports}, Mesh = {Animals; Behavior, Animal; Brain; Psychomotor Performance; Rats; Social Behavior}, Month = {Oct}, Pages = {6652}, Pmc = {PMC4200406}, pmid = {25323637}, Pst = {epublish}, Title = {An experimental task to examine the mirror system in rats}, Volume = {4}, Year = {2014}, url = {papers/Takano_SciRep2014.pdf}} @article{Williams:2006a, Abstract = {An association between autistic spectrum disorder and imitative impairment might result from dysfunction in mirror neurons (MNs) that serve to relate observed actions to motor codings. To explore this hypothesis, we employed a functional magnetic resonance imaging (fMRI) protocol previously used to identify the neural substrate of imitation, and human MN function, to compare 16 adolescent males of normal intelligence with autistic spectrum disorder (ASD) and age, sex and IQ matched controls. In the control group, in accord with previous findings, we identified activity attributable to MNs in areas of the right parietal lobe. Activity in this area was less extensive in the ASD group and was absent during non-imitative action execution. Broca's area was minimally active during imitation in controls. Differential patterns of activity during imitation and action observation in ASD and controls were most evident in an area at the right temporo-parietal junction also associated with a 'theory of mind' (ToM) function. ASD participants also failed to show modulation of left amygdala activity during imitation that was evident in the controls. This may have implications for understanding the imitation of emotional stimuli in ASD. Overall, we suggest that ASD is associated with altered patterns of brain activity during imitation, which could stem from poor integration between areas serving visual, motor, proprioceptive and emotional functions. Such poor integration is likely to adversely affect the development of ToM through imitation as well as other aspects of social cognitive function in ASD.}, Author = {Williams, Justin H G and Waiter, Gordon D and Gilchrist, Anne and Perrett, David I and Murray, Alison D and Whiten, Andrew}, Date-Added = {2017-04-04 23:41:18 +0000}, Date-Modified = {2017-04-04 23:41:18 +0000}, Doi = {10.1016/j.neuropsychologia.2005.06.010}, Journal = {Neuropsychologia}, Journal-Full = {Neuropsychologia}, Mesh = {Adolescent; Amygdala; Asperger Syndrome; Autistic Disorder; Brain; Brain Mapping; Dominance, Cerebral; Female; Humans; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Imitative Behavior; Magnetic Resonance Imaging; Male; Nerve Net; Neurons; Orientation; Parietal Lobe; Personal Construct Theory; Psychomotor Performance; Reference Values; Somatosensory Cortex; Temporal Lobe}, Number = {4}, Pages = {610-21}, pmid = {16140346}, Pst = {ppublish}, Title = {Neural mechanisms of imitation and 'mirror neuron' functioning in autistic spectrum disorder}, Volume = {44}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuropsychologia.2005.06.010}} @article{Bernier:2007, Abstract = {Imitation ability has consistently been shown to be impaired in individuals with autism. A dysfunctional execution/observation matching system has been proposed to account for this impairment. The EEG mu rhythm is believed to reflect an underlying execution/observation matching system. This study investigated evidence of differential mu rhythm attenuation during the observation, execution, and imitation of movements and examined its relation to behaviorally assessed imitation abilities. Fourteen high-functioning adults with autism spectrum disorder (ASD) and 15 IQ- and age-matched typical adults participated. On the behavioral imitation task, adults with ASD demonstrated significantly poorer performance compared to typical adults in all domains of imitation ability. On the EEG task, both groups demonstrated significant attenuation of the mu rhythm when executing an action. However, when observing movement, the individuals with ASD showed significantly reduced attenuation of the mu wave. Behaviorally assessed imitation skills were correlated with degree of mu wave attenuation during observation of movement. These findings suggest that there is execution/observation matching system dysfunction in individuals with autism and that this matching system is related to degree of impairment in imitation abilities.}, Author = {Bernier, R and Dawson, G and Webb, S and Murias, M}, Date-Added = {2017-04-04 23:40:36 +0000}, Date-Modified = {2017-04-04 23:40:36 +0000}, Doi = {10.1016/j.bandc.2007.03.004}, Journal = {Brain Cogn}, Journal-Full = {Brain and cognition}, Mesh = {Adult; Autistic Disorder; Brain; Electroencephalography; Hand Strength; Humans; Imitative Behavior; Male; Neurophysiology; Periodicity}, Month = {Aug}, Number = {3}, Pages = {228-37}, Pmc = {PMC2709976}, pmid = {17451856}, Pst = {ppublish}, Title = {EEG mu rhythm and imitation impairments in individuals with autism spectrum disorder}, Volume = {64}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.bandc.2007.03.004}} @article{Pineda:2005, Abstract = {Existing evidence indicates that mu and other alpha-like rhythms are independent phenomena because of differences in source generation, sensitivity to sensory events, bilateral coherence, frequency, and power. Although mu suppression and enhancement echo sensorimotor processing in frontoparietal networks, they are also sensitive to cognitive and affective influences and likely reflect more than an idling brain state. Mu rhythms are present at early stages of human development and in other mammalian species. They exhibit adaptive and dynamically changing properties, including frequency acceleration and posterior-to-anterior shifts in focus. Furthermore, individuals can learn to control mu rhythms volitionally in a very short period of time. This raises questions about the mu rhythm's open neural architecture and ability to respond to cognitive, affective, and motor imagery, implying an even greater developmental and functional role than has previously been ascribed to it. Recent studies have suggested that mu rhythms reflect downstream modulation of motor cortex by prefrontal mirror neurons, i.e., cells that may play a critical role in imitation learning and the ability to understand the actions of others. It is proposed that mu rhythms represent an important information processing function that links perception and action-specifically, the transformation of "seeing" and "hearing" into "doing." In a broader context, this transformation function results from an entrainment/gating mechanism in which multiple alpha networks (visual-, auditory-, and somatosensory-centered domains), typically producing rhythmic oscillations in a locally independent manner, become coupled and entrained. A global or 'diffuse and distributed alpha system' comes into existence when these independent sources of alpha become coherently engaged in transforming perception to action.}, Author = {Pineda, Jaime A}, Date-Added = {2017-04-04 22:57:22 +0000}, Date-Modified = {2017-04-04 22:57:22 +0000}, Doi = {10.1016/j.brainresrev.2005.04.005}, Journal = {Brain Res Brain Res Rev}, Journal-Full = {Brain research. Brain research reviews}, Mesh = {Animals; Brain; Brain Mapping; Electroencephalography; Hearing; Humans; Mental Processes; Vision, Ocular}, Month = {Dec}, Number = {1}, Pages = {57-68}, pmid = {15925412}, Pst = {ppublish}, Title = {The functional significance of mu rhythms: translating "seeing" and "hearing" into "doing"}, Volume = {50}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainresrev.2005.04.005}} @article{Oberman:2005, Abstract = {Autism spectrum disorders (ASD) are largely characterized by deficits in imitation, pragmatic language, theory of mind, and empathy. Previous research has suggested that a dysfunctional mirror neuron system may explain the pathology observed in ASD. Because EEG oscillations in the mu frequency (8-13 Hz) over sensorimotor cortex are thought to reflect mirror neuron activity, one method for testing the integrity of this system is to measure mu responsiveness to actual and observed movement. It has been established that mu power is reduced (mu suppression) in typically developing individuals both when they perform actions and when they observe others performing actions, reflecting an observation/execution system which may play a critical role in the ability to understand and imitate others' behaviors. This study investigated whether individuals with ASD show a dysfunction in this system, given their behavioral impairments in understanding and responding appropriately to others' behaviors. Mu wave suppression was measured in ten high-functioning individuals with ASD and ten age- and gender-matched control subjects while watching videos of (1) a moving hand, (2) a bouncing ball, and (3) visual noise, or (4) moving their own hand. Control subjects showed significant mu suppression to both self and observed hand movement. The ASD group showed significant mu suppression to self-performed hand movements but not to observed hand movements. These results support the hypothesis of a dysfunctional mirror neuron system in high-functioning individuals with ASD.}, Author = {Oberman, Lindsay M and Hubbard, Edward M and McCleery, Joseph P and Altschuler, Eric L and Ramachandran, Vilayanur S and Pineda, Jaime A}, Date-Added = {2017-04-04 22:19:14 +0000}, Date-Modified = {2017-04-04 22:19:14 +0000}, Doi = {10.1016/j.cogbrainres.2005.01.014}, Journal = {Brain Res Cogn Brain Res}, Journal-Full = {Brain research. Cognitive brain research}, Mesh = {Adolescent; Adult; Alpha Rhythm; Autistic Disorder; Case-Control Studies; Child; Electroencephalography; Female; Humans; Imitative Behavior; Inhibition (Psychology); Male; Mental Processes; Middle Aged; Movement; Neurons; Psychomotor Performance; Spectrum Analysis; Visual Perception}, Month = {Jul}, Number = {2}, Pages = {190-8}, pmid = {15993757}, Pst = {ppublish}, Title = {EEG evidence for mirror neuron dysfunction in autism spectrum disorders}, Volume = {24}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cogbrainres.2005.01.014}} @article{Evans:2013, Abstract = {Within the framework of the radical pair mechanism, magnetic fields may alter the rate and yields of chemical reactions involving spin-correlated radical pairs as intermediates. Such effects have been studied in detail in a variety of chemical systems both experimentally and theoretically. In recent years, there has been growing interest in whether such magnetic field effects (MFEs) also occur in biological systems, a question driven most notably by the increasing body of evidence for the involvement of such effects in the magnetic compass sense of animals. The blue-light photoreceptor cryptochrome is placed at the centre of this debate and photoexcitation of its bound flavin cofactor has indeed been shown to result in the formation of radical pairs. Here, we review studies of MFEs on free flavins in model systems as well as in blue-light photoreceptor proteins and discuss the properties that are crucial in determining the magnetosensitivity of these systems.}, Author = {Evans, Emrys W and Dodson, Charlotte A and Maeda, Kiminori and Biskup, Till and Wedge, C J and Timmel, Christiane R}, Date-Added = {2017-03-06 22:26:23 +0000}, Date-Modified = {2017-03-06 22:26:23 +0000}, Doi = {10.1098/rsfs.2013.0037}, Journal = {Interface Focus}, Journal-Full = {Interface focus}, Keywords = {cryptochrome; magnetic compass; magnetic field effect; photolyase; radical pair mechanism}, Month = {Oct}, Number = {5}, Pages = {20130037}, Pmc = {PMC3915827}, pmid = {24511388}, Pst = {ppublish}, Title = {Magnetic field effects in flavoproteins and related systems}, Volume = {3}, Year = {2013}, url = {papers/Evans_InterfaceFocus2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1098/rsfs.2013.0037}} @article{Torii:2009, Abstract = {The cerebral cortex is a laminated sheet of neurons composed of the arrays of intersecting radial columns. During development, excitatory projection neurons originating from the proliferative units at the ventricular surface of the embryonic cerebral vesicles migrate along elongated radial glial fibres to form a cellular infrastructure of radial (vertical) ontogenetic columns in the overlaying cortical plate. However, a subpopulation of these clonally related neurons also undergoes a short lateral shift and transfers from their parental to the neighbouring radial glial fibres, and intermixes with neurons originating from neighbouring proliferative units. This columnar organization acts as the primary information processing unit in the cortex. The molecular mechanisms, role and significance of this lateral dispersion for cortical development are not understood. Here we show that an Eph receptor A (EphA) and ephrin A (Efna) signalling-dependent shift in the allocation of clonally related neurons is essential for the proper assembly of cortical columns. In contrast to the relatively uniform labelling of the developing cortical plate by various molecular markers and retrograde tracers in wild-type mice, we found alternating labelling of columnar compartments in Efna knockout mice that are caused by impaired lateral dispersion of migrating neurons rather than by altered cell production or death. Furthermore, in utero electroporation showed that lateral dispersion depends on the expression levels of EphAs and ephrin-As during neuronal migration. This so far unrecognized mechanism for lateral neuronal dispersion seems to be essential for the proper intermixing of neuronal types in the cortical columns, which, when disrupted, might contribute to neuropsychiatric disorders associated with abnormal columnar organization.}, Author = {Torii, Masaaki and Hashimoto-Torii, Kazue and Levitt, Pat and Rakic, Pasko}, Date-Added = {2017-02-23 22:15:12 +0000}, Date-Modified = {2017-02-23 22:15:12 +0000}, Doi = {10.1038/nature08362}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Cell Movement; Cerebral Cortex; Ephrins; Mice; Mice, Knockout; Neocortex; Neurons; Organogenesis; Rats; Receptors, Eph Family; Signal Transduction}, Month = {Sep}, Number = {7263}, Pages = {524-8}, Pmc = {PMC2874978}, pmid = {19759535}, Pst = {ppublish}, Title = {Integration of neuronal clones in the radial cortical columns by EphA and ephrin-A signalling}, Volume = {461}, Year = {2009}, url = {papers/Torii_Nature2009.pdf}, Bdsk-File-2 = {papers/Torii_Nature2009a.pdf}} @article{Kania:2016, Abstract = {Eph receptor Tyr kinases and their membrane-tethered ligands, the ephrins, elicit short-distance cell-cell signalling and thus regulate many developmental processes at the interface between pattern formation and morphogenesis, including cell sorting and positioning, and the formation of segmented structures and ordered neural maps. Their roles extend into adulthood, when ephrin-Eph signalling regulates neuronal plasticity, homeostatic events and disease processes. Recently, new insights have been gained into the mechanisms of ephrin-Eph signalling in different cell types, and into the physiological importance of ephrin-Eph in different organs and in disease, raising questions for future research directions.}, Author = {Kania, Artur and Klein, R{\"u}diger}, Date-Added = {2017-02-23 22:15:03 +0000}, Date-Modified = {2017-02-23 22:15:03 +0000}, Doi = {10.1038/nrm.2015.16}, Journal = {Nat Rev Mol Cell Biol}, Journal-Full = {Nature reviews. Molecular cell biology}, Mesh = {Animals; Ephrins; Growth and Development; Humans; Receptors, Eph Family; Signal Transduction}, Month = {Apr}, Number = {4}, Pages = {240-56}, pmid = {26790531}, Pst = {ppublish}, Title = {Mechanisms of ephrin-Eph signalling in development, physiology and disease}, Volume = {17}, Year = {2016}, url = {papers/Kania_NatRevMolCellBiol2016.pdf}} @article{Shibuki:2003, Abstract = {We used autofluorescence of mitochondrial flavoproteins to image cortical neural activity in the rat. Green autofluorescence in blue light was examined in slices obtained from rat cerebral cortex. About half of the basal autofluorescence was modulated by the presence or absence of O2 or glucose in the medium. Repetitive electrical stimulation at 20 Hz for 1 s produced a localized fluorescence increase in the slices. The amplitude of the increase was 27 +/- 2 % (mean +/- S.D., n = 35). Tetrodotoxin or diphenyleneiodonium, an inhibitor of flavoproteins, blocked the autofluorescence responses. The autofluorescence responses were not observed in slices perfused with calcium-, glucose- or O2-free medium. In the primary somatosensory cortex of rats anaesthetized with urethane (1.5 g kg-1, I.P.), an activity-dependent increase in autofluorescence of 20 +/- 4 % (n = 6) was observed after electrical cortical stimulation at 100 Hz for 1 s, and an increase of 2.6 +/- 0.5 % (n = 33) after vibratory skin stimulation at 50 Hz for 1 s applied to the plantar hindpaw. These responses were large enough to allow visualization of the neural activity without having to average a number of trials. The distribution of the fluorescence responses after electrical or vibratory skin stimulation was comparable to that of the cortical field potentials in the same rats. The fluorescence responses were followed by an increase in arterial blood flow. The former were resistant to an inhibitor of nitric oxide synthase, while the latter was inhibited. Thus, activity-dependent changes in the autofluorescence of flavoproteins are useful for functional brain imaging in vivo.}, Author = {Shibuki, Katsuei and Hishida, Ryuichi and Murakami, Hiroatsu and Kudoh, Masaharu and Kawaguchi, Tadashi and Watanabe, Masatoshi and Watanabe, Shunsuke and Kouuchi, Takeshi and Tanaka, Ryuichi}, Date-Added = {2017-02-20 19:54:00 +0000}, Date-Modified = {2017-02-20 19:54:00 +0000}, Doi = {10.1113/jphysiol.2003.040709}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Anesthesia; Animals; Calcium; Cerebrovascular Circulation; Electric Stimulation; Evoked Potentials, Somatosensory; Flavoproteins; Fluorescence; Fluorescent Dyes; Green Fluorescent Proteins; Hemodynamics; Heterocyclic Compounds, 3-Ring; Image Interpretation, Computer-Assisted; Luminescent Proteins; Male; Rats; Rats, Wistar; Somatosensory Cortex; Vibration}, Month = {Jun}, Number = {Pt 3}, Pages = {919-27}, Pmc = {PMC2342977}, pmid = {12730344}, Pst = {ppublish}, Title = {Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence}, Volume = {549}, Year = {2003}, url = {papers/Shibuki_JPhysiol2003.pdf}} @article{Husson:2007, Abstract = {Neuronal autofluorescence, which results from the oxidation of flavoproteins in the electron transport chain, has recently been used to map cortical responses to sensory stimuli. This approach could represent a substantial improvement over other optical imaging methods because it is a direct (i.e., nonhemodynamic) measure of neuronal metabolism. However, its application to functional imaging has been limited because strong responses have been reported only in rodents. In this study, we demonstrate that autofluorescence imaging (AFI) can be used to map the functional organization of primary visual cortex in both mouse and cat. In cat area 17, orientation preference maps generated by AFI had the classic pinwheel structure and matched those generated by intrinsic signal imaging in the same imaged field. The spatiotemporal profile of the autofluorescence signal had several advantages over intrinsic signal imaging, including spatially restricted fluorescence throughout its response duration, reduced susceptibility to vascular artifacts, an improved spatial response profile, and a faster time course. These results indicate that AFI is a robust and useful measure of large-scale cortical activity patterns in visual mammals.}, Author = {Husson, T Robert and Mallik, Atul K and Zhang, Jing X and Issa, Naoum P}, Date-Added = {2017-02-20 19:53:52 +0000}, Date-Modified = {2017-02-20 19:53:52 +0000}, Doi = {10.1523/JNEUROSCI.2156-07.2007}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Brain Mapping; Cats; Female; Flavoproteins; Fluorescence; Mice; Photic Stimulation; Reaction Time; Retinoscopy; Visual Cortex}, Month = {Aug}, Number = {32}, Pages = {8665-75}, pmid = {17687044}, Pst = {ppublish}, Title = {Functional imaging of primary visual cortex using flavoprotein autofluorescence}, Volume = {27}, Year = {2007}, url = {papers/Husson_JNeurosci2007.pdf}} @article{Michael:2014, Abstract = {Large-scale brain activity patterns can be visualized by optical imaging of intrinsic signals (OIS) based on activity-dependent changes in the blood oxygenation level. Another method, flavoprotein autofluorescence imaging (AFI), exploits the mitochondrial flavoprotein autofluorescence, which is enhanced during neuronal activity. In birds, topographic mapping of visual space has been shown in the visual wulst, the avian homologue of the mammalian visual cortex by using OIS. We here applied the AFI method to visualize topographic maps in the visual wulst because with OIS, which depends on blood flow changes, blood vessel artifacts often obscure brain activity maps. We then compared both techniques quantitatively in zebra finches and in C57Bl/6J mice using the same setup and stimulation conditions. In addition to experiments with craniotomized animals, we also examined mice with intact skull (in zebra finches, intact skull imaging is not feasible probably due to the skull construction). In craniotomized animals, retinotopic maps were obtained by both methods in both species. Using AFI, artifacts caused by blood vessels were generally reduced, the magnitude of neuronal activity significantly higher and the retinotopic map quality better than that obtained by OIS in both zebra finches and mice. In contrast, our measurements in non-craniotomized mice did not reveal any quantitative differences between the two methods. Our results thus suggest that AFI is the method of choice for investigations of visual processing in zebra finches. In mice, however, if researchers decide to use the advantages of imaging through the intact skull, they will not be able to exploit the higher signals obtainable by the AFI-method.}, Author = {Michael, Neethu and Bischof, Hans-Joachim and L{\"o}wel, Siegrid}, Date-Added = {2017-02-20 19:53:44 +0000}, Date-Modified = {2017-02-20 19:53:44 +0000}, Doi = {10.1371/journal.pone.0085225}, Journal = {PLoS One}, Journal-Full = {PloS one}, Mesh = {Animals; Female; Finches; Flavoproteins; Male; Mice; Optical Imaging; Visual Cortex}, Number = {1}, Pages = {e85225}, Pmc = {PMC3882276}, pmid = {24400130}, Pst = {epublish}, Title = {Flavoprotein autofluorescence imaging of visual system activity in zebra finches and mice}, Volume = {9}, Year = {2014}, url = {papers/Michael_PLoSOne2014.PDF}} @article{Matos:2015, Abstract = {BACKGROUND: Adenosine A2A receptors (A2AR) modulate dopamine and glutamate signaling and thereby may influence some of the psychomotor and cognitive processes associated with schizophrenia. Because astroglial A2AR regulate the availability of glutamate, we hypothesized that they might play an unprecedented role in some of the processes leading to the development of schizophrenia, which we investigated using a mouse line with a selective deletion of A2AR in astrocytes (Gfa2-A2AR knockout [KO] mice]. METHODS: We examined Gfa2-A2AR KO mice for behaviors thought to recapitulate some features of schizophrenia, namely enhanced MK-801 psychomotor response (positive symptoms) and decreased working memory (cognitive symptoms). In addition, we probed for neurochemical alterations in the glutamatergic circuitry, evaluating glutamate uptake and release and the levels of key proteins defining glutamatergic signaling (glutamate transporter-I [GLT-I], N-methyl-D-aspartate receptors [NMDA-R] and α-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors [AMPA-R]) to provide a mechanistic understanding of the phenotype encountered. RESULTS: We show that Gfa2-A2AR KO mice exhibited enhanced MK-801 psychomotor response and decreased working memory; this was accompanied by a disruption of glutamate homeostasis characterized by aberrant GLT-I activity, increased presynaptic glutamate release, NMDA-R 2B subunit upregulation, and increased internalization of AMPA-R. Accordingly, selective GLT-I inhibition or blockade of GluR1/2 endocytosis prevented the psychomotor and cognitive phenotypes in Gfa2-A2AR KO mice, namely in the nucleus accumbens. CONCLUSIONS: These results show that the dysfunction of astrocytic A2AR, by controlling GLT-I activity, triggers an astrocyte-to-neuron wave of communication resulting in disrupted glutamate homeostasis, thought to underlie several endophenotypes relevant to schizophrenia.}, Author = {Matos, Marco and Shen, Hai-Ying and Augusto, Elisabete and Wang, Yumei and Wei, Catherine J and Wang, Yu Tian and Agostinho, Paula and Boison, Detlev and Cunha, Rodrigo A and Chen, Jiang-Fan}, Date-Added = {2017-01-19 20:37:58 +0000}, Date-Modified = {2017-01-19 20:37:58 +0000}, Doi = {10.1016/j.biopsych.2015.02.026}, Journal = {Biol Psychiatry}, Journal-Full = {Biological psychiatry}, Keywords = {A(2A)R; Adenosine; Astrocytes; GLT-I; NMDA-R; Schizophrenia}, Mesh = {Animals; Astrocytes; Cognition Disorders; Disease Models, Animal; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Transporter 2; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Glutamic Acid; Homeostasis; Kainic Acid; Locomotion; Mice; Mice, Inbred C57BL; Mice, Transgenic; Psychomotor Disorders; Pyrimidines; Receptor, Adenosine A2A; Receptors, N-Methyl-D-Aspartate; Synaptosomes; Time Factors; Triazoles}, Month = {Dec}, Number = {11}, Pages = {763-74}, Pmc = {PMC4714966}, pmid = {25869810}, Pst = {ppublish}, Title = {Deletion of adenosine A2A receptors from astrocytes disrupts glutamate homeostasis leading to psychomotor and cognitive impairment: relevance to schizophrenia}, Volume = {78}, Year = {2015}, url = {papers/Matos_BiolPsychiatry2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.biopsych.2015.02.026}} @article{Silva:2013, Abstract = {Consumption of certain substances during pregnancy can interfere with brain development, leading to deleterious long-term neurological and cognitive impairments in offspring. To test whether modulators of adenosine receptors affect neural development, we exposed mouse dams to a subtype-selective adenosine type 2A receptor (A2AR) antagonist or to caffeine, a naturally occurring adenosine receptor antagonist, during pregnancy and lactation. We observed delayed migration and insertion of γ-aminobutyric acid (GABA) neurons into the hippocampal circuitry during the first postnatal week in offspring of dams treated with the A2AR antagonist or caffeine. This was associated with increased neuronal network excitability and increased susceptibility to seizures in response to a seizure-inducing agent. Adult offspring of mouse dams exposed to A2AR antagonists during pregnancy and lactation displayed loss of hippocampal GABA neurons and some cognitive deficits. These results demonstrate that exposure to A2AR antagonists including caffeine during pregnancy and lactation in rodents may have adverse effects on the neural development of their offspring.}, Author = {Silva, Carla G and M{\'e}tin, Christine and Fazeli, Walid and Machado, Nuno J and Darmopil, Sanja and Launay, Pierre-Serge and Ghestem, Antoine and Nesa, Marie-Pascale and Bassot, Emilie and Szab{\'o}, Eszter and Baqi, Younis and M{\"u}ller, Christa E and Tom{\'e}, Angelo R and Ivanov, Anton and Isbrandt, Dirk and Zilberter, Yuri and Cunha, Rodrigo A and Esclapez, Monique and Bernard, Christophe}, Date-Added = {2017-01-19 20:36:44 +0000}, Date-Modified = {2017-01-19 20:36:44 +0000}, Doi = {10.1126/scitranslmed.3006258}, Journal = {Sci Transl Med}, Journal-Full = {Science translational medicine}, Mesh = {Aging; Animals; Animals, Newborn; Brain; Caffeine; Cell Movement; Cognition Disorders; Disease Susceptibility; Female; Fetus; GABAergic Neurons; Glutamates; Green Fluorescent Proteins; Haplorhini; Hippocampus; Mice; Nerve Net; Pregnancy; Purinergic P1 Receptor Antagonists; Rats; Receptors, Adenosine A2; Seizures; Telencephalon}, Month = {Aug}, Number = {197}, Pages = {197ra104}, pmid = {23926202}, Pst = {ppublish}, Title = {Adenosine receptor antagonists including caffeine alter fetal brain development in mice}, Volume = {5}, Year = {2013}, url = {papers/Silva_SciTranslMed2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/scitranslmed.3006258}} @article{Aden:2000, Abstract = {Maternal caffeine intake has been suggested to influence the offspring. We have studied the effects of maternal caffeine intake on adenosine and GABA receptors, targets for caffeine, during development of the rat brain. Caffeine (0.3 g/L) was added to the drinking water of rat dams during pregnancy and early postnatal life. Adenosine A1 and A2A and GABAA receptor development was studied using receptor autoradiography and in situ hybridization. Pups were examined on embryonic d 14 (E14), E18, E21, 2 h after birth (P2h), P24h, postnatal d 3 (P3), P7, P14, and P21. Adenosine A, receptor mRNA was detected at E14 and receptors at E18. A1 mRNA levels increased from the level reached at E18 between P3 and P14 (maximally a doubling), whereas A, receptors, studied by [3H]-1,3-dipropyl-8-cyclopentyl xanthine binding, increased later and to a much larger extent (about 10-fold) postnatally. Caffeine treatment had no significant effect on adenosine A1 receptors or on A1 receptor mRNA. A2A mRNA had reached adult levels by E18, whereas receptor levels were low or undetectable before birth and increased dramatically until P14. Caffeine did not influence A2A receptors or A2A receptor mRNA at any stage during development. [3H]-flunitrazepam binding, representing GABAA receptors, showed large regional variations during ontogeny, but there were no clear differences between the caffeine-exposed and the nonexposed pups. Thus, exposure to a low dose of caffeine during gestation and postnatal life had only minor effects on development of adenosine A, and A2A receptors and GABAA receptors in the rat brain.}, Author = {Ad{\'e}n, U and Herlenius, E and Tang, L Q and Fredholm, B B}, Date-Added = {2017-01-19 20:35:56 +0000}, Date-Modified = {2017-01-19 20:35:56 +0000}, Doi = {10.1203/00006450-200008000-00010}, Journal = {Pediatr Res}, Journal-Full = {Pediatric research}, Mesh = {Adenosine; Animals; Animals, Newborn; Autoradiography; Brain; Caffeine; Female; Gene Expression Regulation, Developmental; In Situ Hybridization; Phenethylamines; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Receptors, GABA-A; Receptors, Purinergic P1; Tritium; Xanthines}, Month = {Aug}, Number = {2}, Pages = {177-83}, pmid = {10926292}, Pst = {ppublish}, Title = {Maternal caffeine intake has minor effects on adenosine receptor ontogeny in the rat brain}, Volume = {48}, Year = {2000}, url = {papers/Adén_PediatrRes2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1203/00006450-200008000-00010}} @article{Schwalfenberg:2013, Abstract = {Background. Increasing concern is evident about contamination of foodstuffs and natural health products. Methods. Common off-the-shelf varieties of black, green, white, and oolong teas sold in tea bags were used for analysis in this study. Toxic element testing was performed on 30 different teas by analyzing (i) tea leaves, (ii) tea steeped for 3-4 minutes, and (iii) tea steeped for 15-17 minutes. Results were compared to existing preferred endpoints. Results. All brewed teas contained lead with 73% of teas brewed for 3 minutes and 83% brewed for 15 minutes having lead levels considered unsafe for consumption during pregnancy and lactation. Aluminum levels were above recommended guidelines in 20% of brewed teas. No mercury was found at detectable levels in any brewed tea samples. Teas contained several beneficial elements such as magnesium, calcium, potassium, and phosphorus. Of trace minerals, only manganese levels were found to be excessive in some black teas. Conclusions. Toxic contamination by heavy metals was found in most of the teas sampled. Some tea samples are considered unsafe. There are no existing guidelines for routine testing or reporting of toxicant levels in "naturally" occurring products. Public health warnings or industry regulation might be indicated to protect consumer safety.}, Author = {Schwalfenberg, Gerry and Genuis, Stephen J and Rodushkin, Ilia}, Date-Added = {2017-01-19 20:34:51 +0000}, Date-Modified = {2017-01-19 20:34:51 +0000}, Doi = {10.1155/2013/370460}, Journal = {J Toxicol}, Journal-Full = {Journal of toxicology}, Pages = {370460}, Pmc = {PMC3821942}, pmid = {24260033}, Pst = {ppublish}, Title = {The benefits and risks of consuming brewed tea: beware of toxic element contamination}, Volume = {2013}, Year = {2013}, url = {papers/Schwalfenberg_JToxicol2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1155/2013/370460}} @article{Aden:2003, Abstract = {BACKGROUND AND PURPOSE: Cerebral hypoxic ischemia (HI) is an important cause of brain injury in the newborn infant. Adenosine is believed to protect against HI brain damage. However, the roles of the different adenosine receptors are unclear, particularly in young animals. We examined the role of adenosine A2A receptors (A2AR) using 7-day-old A2A knockout (A2AR(-/-)) mice in a model of HI. METHODS: HI was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated with the use of histopathological scoring and measurements of residual brain areas at 5 days, 3 weeks, and 3 months after HI. Behavioral evaluation of brain injury by locomotor activity, rotarod, and beam-walking test was made 3 weeks and 3 months after HI. Cortical cerebral blood flow, assessed by laser-Doppler flowmetry, and rectal temperature were measured during HI. RESULTS: Reduction in cortical cerebral blood flow during HI and rectal temperature did not differ between wild-type (A2AR(+/+)) and knockout mice. In the A2AR(-/-) animals, brain injury was aggravated compared with wild-type mice. The A2AR(-/-) mice subjected to HI displayed increased forward locomotion and impaired rotarod performance in adulthood compared with A2AR(+/+) mice subjected to HI, whereas beam-walking performance was similarly defective in both groups. CONCLUSIONS: These results suggest that, in contrast to the situation in adult animals, A2AR play an important protective role in neonatal HI brain injury.}, Author = {Ad{\'e}n, Ulrika and Halldner, Linda and Lagercrantz, Hugo and Dalmau, Ishar and Ledent, Catherine and Fredholm, Bertil B}, Date-Added = {2017-01-19 20:33:07 +0000}, Date-Modified = {2017-01-19 20:33:07 +0000}, Doi = {10.1161/01.STR.0000060204.67672.8B}, Journal = {Stroke}, Journal-Full = {Stroke}, Mesh = {Animals; Animals, Newborn; Atmosphere Exposure Chambers; Behavior, Animal; Blood Flow Velocity; Body Temperature; Brain; Carotid Arteries; Cerebrovascular Circulation; Disease Models, Animal; Disease Progression; Hypoxia, Brain; Hypoxia-Ischemia, Brain; Laser-Doppler Flowmetry; Ligation; Mice; Mice, Knockout; Receptor, Adenosine A2A; Receptors, Purinergic P1; Survival Rate}, Month = {Mar}, Number = {3}, Pages = {739-44}, pmid = {12624301}, Pst = {ppublish}, Title = {Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice}, Volume = {34}, Year = {2003}, url = {papers/Adén_Stroke2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.STR.0000060204.67672.8B}} @article{Kinkead:2009, Abstract = {STUDY OBJECTIVES: Neonatal maternal separation (NMS) disrupts development of cardiorespiratory regulation. Adult male rats previously subjected to NMS are hypertensive and show a hypoxic ventilatory response greater than that of controls. These results have been obtained in awake or anesthetised animals, and the consequences of NMS on respiratory control during normal sleep are unknown. This study tested the following. HYPOTHESES: NMS augments respiratory variability across sleep-wake states, and NMS-related enhancement of the hypoxic ventilatory response occurs during sleep. METHODS: Two groups of adult rats were used: controls (no treatment) and rats subjected to NMS. Ventilatory activity, coefficient of variation, and hypoxic ventilatory response were compared between groups and across sleep-wake states. SUBJECTS: Male Sprague Dawley rats-NMS: n=11; controls: n=10. Pups subjected to NMS were isolated from their mother for 3 hours per day from postnatal days 3 to 12. Controls were undisturbed. MEASUREMENTS AND RESULTS: At adulthood, sleep-wake states were monitored by telemetry, and ventilatory activity was measured using whole-body plethysmography. Sleep and breathing were measured for 2.5 hours (in the morning) while the rats were breathing room air. Data were analysed in 20-second epochs. Rats were then exposed to a brief (90-sec) hypoxic episode (nadir = 12% O2) to measure the hypoxic ventilatory response. The coefficient of variability for tidal volume and breathing frequency decreased during sleep but remained more elevated in NMS rats than in controls. During non-rapid eye movement sleep, the breathing-frequency response to hypoxia of NMS rats was significantly greater than that of controls. CONCLUSION: Neonatal maternal separation results in persistent disruption of respiratory control during sleep.}, Author = {Kinkead, Richard and Montandon, Gaspard and Bairam, Aida and Lajeunesse, Yves and Horner, Richard}, Date-Added = {2017-01-19 20:32:11 +0000}, Date-Modified = {2017-01-19 20:32:11 +0000}, Journal = {Sleep}, Journal-Full = {Sleep}, Mesh = {Animals; Animals, Newborn; Behavior, Animal; Electroencephalography; Electromyography; Hypoxia; Male; Maternal Deprivation; Plethysmography, Whole Body; Pulmonary Ventilation; Rats; Rats, Sprague-Dawley; Respiration; Respiratory Mechanics; Sleep; Sleep Apnea Syndromes; Telemetry; Tidal Volume; Time Factors; Wakefulness}, Month = {Dec}, Number = {12}, Pages = {1611-20}, Pmc = {PMC2786045}, pmid = {20041597}, Pst = {ppublish}, Title = {Neonatal maternal separation disrupts regulation of sleep and breathing in adult male rats}, Volume = {32}, Year = {2009}} @article{Montandon:2009, Abstract = {Caffeine is commonly used clinically to treat apnoeas and unstable breathing associated with premature birth. Caffeine antagonizes adenosine receptors and acts as an efficient respiratory stimulant in neonates. Owing to its persistent effects on adenosine receptor expression in the brain, neonatal caffeine administration also has significant effects on maturation of the respiratory control system. However, since adenosine receptors are critically involved in sleep regulation, and sleep also modulates breathing, we tested the hypothesis that neonatal caffeine treatment disrupts regulation of sleep and breathing in the adult rat. Neonatal caffeine treatment (15 mg kg(-1) day(-1)) was administered from postnatal days 3-12. At adulthood (8-10 weeks old), sleep and breathing were measured with a telemetry system and whole-body plethysmography respectively. In adult rats treated with caffeine during the neonatal period, sleep time was reduced, sleep onset latency was increased, and non-rapid eye movement (non-REM) sleep was fragmented compared to controls. Ventilation at rest was higher in caffeine-treated adult rats compared to controls across sleep/wake states. Hypercapnic ventilatory responses were significantly reduced in caffeine-treated rats compared to control rats across sleep/wake states. Additional experiments in adult anaesthetized rats showed that at similar levels of arterial blood gases, phrenic nerve activity was enhanced in caffeine-treated rats. This study demonstrates that administration of caffeine in the neonatal period alters respiratory control system activity in awake and sleeping rats, as well as in the anaesthetized rats, and also has persistent disrupting effects on sleep that are apparent in adult rats.}, Author = {Montandon, Gaspard and Horner, Richard L and Kinkead, Richard and Bairam, Aida}, Date-Added = {2017-01-19 20:32:09 +0000}, Date-Modified = {2017-01-19 20:32:09 +0000}, Doi = {10.1113/jphysiol.2009.171918}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Age Factors; Animals; Animals, Newborn; Blood Gas Analysis; Caffeine; Male; Pulmonary Ventilation; Rats; Rats, Sprague-Dawley; Sleep; Time Factors; Wakefulness}, Month = {Nov}, Number = {Pt 22}, Pages = {5493-507}, Pmc = {PMC2793879}, pmid = {19770189}, Pst = {ppublish}, Title = {Caffeine in the neonatal period induces long-lasting changes in sleep and breathing in adult rats}, Volume = {587}, Year = {2009}, url = {papers/Montandon_JPhysiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2009.171918}} @article{Ma:2016, Abstract = {Although modern techniques such as two-photon microscopy can now provide cellular-level three-dimensional imaging of the intact living brain, the speed and fields of view of these techniques remain limited. Conversely, two-dimensional wide-field optical mapping (WFOM), a simpler technique that uses a camera to observe large areas of the exposed cortex under visible light, can detect changes in both neural activity and haemodynamics at very high speeds. Although WFOM may not provide single-neuron or capillary-level resolution, it is an attractive and accessible approach to imaging large areas of the brain in awake, behaving mammals at speeds fast enough to observe widespread neural firing events, as well as their dynamic coupling to haemodynamics. Although such wide-field optical imaging techniques have a long history, the advent of genetically encoded fluorophores that can report neural activity with high sensitivity, as well as modern technologies such as light emitting diodes and sensitive and high-speed digital cameras have driven renewed interest in WFOM. To facilitate the wider adoption and standardization of WFOM approaches for neuroscience and neurovascular coupling research, we provide here an overview of the basic principles of WFOM, considerations for implementation of wide-field fluorescence imaging of neural activity, spectroscopic analysis and interpretation of results.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.}, Author = {Ma, Ying and Shaik, Mohammed A and Kim, Sharon H and Kozberg, Mariel G and Thibodeaux, David N and Zhao, Hanzhi T and Yu, Hang and Hillman, Elizabeth M C}, Date-Added = {2017-01-19 20:30:19 +0000}, Date-Modified = {2017-01-19 20:30:19 +0000}, Doi = {10.1098/rstb.2015.0360}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {GCaMP; fluorescence; haemodynamics; neurovascular coupling; optical imaging; spectroscopy}, Month = {Oct}, Number = {1705}, Pmc = {PMC5003860}, pmid = {27574312}, Pst = {ppublish}, Title = {Wide-field optical mapping of neural activity and brain haemodynamics: considerations and novel approaches}, Volume = {371}, Year = {2016}, url = {papers/Ma_PhilosTransRSocLondBBiolSci2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1098/rstb.2015.0360}} @article{Button:2013, Abstract = {A study with low statistical power has a reduced chance of detecting a true effect, but it is less well appreciated that low power also reduces the likelihood that a statistically significant result reflects a true effect. Here, we show that the average statistical power of studies in the neurosciences is very low. The consequences of this include overestimates of effect size and low reproducibility of results. There are also ethical dimensions to this problem, as unreliable research is inefficient and wasteful. Improving reproducibility in neuroscience is a key priority and requires attention to well-established but often ignored methodological principles.}, Author = {Button, Katherine S and Ioannidis, John P A and Mokrysz, Claire and Nosek, Brian A and Flint, Jonathan and Robinson, Emma S J and Munaf{\`o}, Marcus R}, Date-Added = {2017-01-19 20:24:24 +0000}, Date-Modified = {2017-01-19 20:24:24 +0000}, Doi = {10.1038/nrn3475}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Humans; Neurosciences; Probability; Reproducibility of Results; Sample Size}, Month = {May}, Number = {5}, Pages = {365-76}, pmid = {23571845}, Pst = {ppublish}, Title = {Power failure: why small sample size undermines the reliability of neuroscience}, Volume = {14}, Year = {2013}, url = {papers/Button_NatRevNeurosci2013.pdf}} @article{Adolphs:1995, Abstract = {We have previously reported that bilateral amygdala damage in humans compromises the recognition of fear in facial expressions while leaving intact recognition of face identity (Adolphs et al., 1994). The present study aims at examining questions motivated by this finding. We addressed the possibility that unilateral amygdala damage might be sufficient to impair recognition of emotional expressions. We also obtained further data on our subject with bilateral amygdala damage, in order to elucidate possible mechanisms that could account for the impaired recognition of expressions of fear. The results show that bilateral, but not unilateral, damage to the human amygdala impairs the processing of fearful facial expressions. This impairment appears to result from an insensitivity to the intensity of fear expressed by faces. We also confirmed a double dissociation between the recognition of facial expressions of fear, and the recognition of identity of a face: these two processes can be impaired independently, lending support to the idea that they are subserved in part by anatomically separate neural systems. Based on our data, and on what is known about the amygdala's connectivity, we propose that the amygdala is required to link visual representations of facial expressions, on the one hand, with representations that constitute the concept of fear, on the other. Preliminary data suggest the amygdala's role extends to both recognition and recall of fearful facial expressions.}, Author = {Adolphs, R and Tranel, D and Damasio, H and Damasio, A R}, Date-Added = {2016-12-02 18:40:54 +0000}, Date-Modified = {2016-12-02 18:40:54 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Amygdala; Art; Brain Damage, Chronic; Brain Diseases; Emotions; Face; Facial Expression; Fear; Humans; Magnetic Resonance Imaging; Neuropsychological Tests; Pattern Recognition, Visual; Social Behavior}, Month = {Sep}, Number = {9}, Pages = {5879-91}, pmid = {7666173}, Pst = {ppublish}, Title = {Fear and the human amygdala}, Volume = {15}, Year = {1995}, url = {papers/Adolphs_JNeurosci1995.pdf}} @article{Smit-Rigter:2016, Abstract = {Mitochondria buffer intracellular Ca(2+) and provide energy [1]. Because synaptic structures with high Ca(2+) buffering [2-4] or energy demand [5] are often localized far away from the soma, mitochondria are actively transported to these sites [6-11]. Also, the removal and degradation of mitochondria are tightly regulated [9, 12, 13], because dysfunctional mitochondria are a source of reactive oxygen species, which can damage the cell [14]. Deficits in mitochondrial trafficking have been proposed to contribute to the pathogenesis of Parkinson's disease, schizophrenia, amyotrophic lateral sclerosis, optic atrophy, and Alzheimer's disease [13, 15-19]. In neuronal cultures, about a third of mitochondria are motile, whereas the majority remains stationary for several days [8, 20]. Activity-dependent mechanisms cause mitochondria to stop at synaptic sites [7, 8, 20, 21], which affects synapse function and maintenance. Reducing mitochondrial content in dendrites decreases spine density [22, 23], whereas increasing mitochondrial content or activity increases it [7]. These bidirectional interactions between synaptic activity and mitochondrial trafficking suggest that mitochondria may regulate synaptic plasticity. Here we investigated the dynamics of mitochondria in relation to axonal boutons of neocortical pyramidal neurons for the first time in vivo. We find that under these circumstances practically all mitochondria are stationary, both during development and in adulthood. In adult visual cortex, mitochondria are preferentially localized at putative boutons, where they remain for several days. Retinal-lesion-induced cortical plasticity increases turnover of putative boutons but leaves mitochondrial turnover unaffected. We conclude that in visual cortex in vivo, mitochondria are less dynamic than in vitro, and that structural plasticity does not affect mitochondrial dynamics.}, Author = {Smit-Rigter, Laura and Rajendran, Rajeev and Silva, Catia A P and Spierenburg, Liselot and Groeneweg, Femke and Ruimschotel, Emma M and van Versendaal, Danielle and van der Togt, Chris and Eysel, Ulf T and Heimel, J Alexander and Lohmann, Christian and Levelt, Christiaan N}, Date-Added = {2016-12-02 18:40:11 +0000}, Date-Modified = {2016-12-02 18:40:11 +0000}, Doi = {10.1016/j.cub.2016.07.033}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Month = {Oct}, Number = {19}, Pages = {2609-2616}, pmid = {27641766}, Pst = {ppublish}, Title = {Mitochondrial Dynamics in Visual Cortex Are Limited In Vivo and Not Affected by Axonal Structural Plasticity}, Volume = {26}, Year = {2016}, url = {papers/Smit-Rigter_CurrBiol2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2016.07.033}} @article{Winnubst:2015, Abstract = {Spontaneous activity fine-tunes neuronal connections in the developing brain. To explore the underlying synaptic plasticity mechanisms, we monitored naturally occurring changes in spontaneous activity at individual synapses with whole-cell patch-clamp recordings and simultaneous calcium imaging in the mouse visual cortex in vivo. Analyzing activity changes across large populations of synapses revealed a simple and efficient local plasticity rule: synapses that exhibit low synchronicity with nearby neighbors (<12 μm) become depressed in their transmission frequency. Asynchronous electrical stimulation of individual synapses in hippocampal slices showed that this is due to a decrease in synaptic transmission efficiency. Accordingly, experimentally increasing local synchronicity, by stimulating synapses in response to spontaneous activity at neighboring synapses, stabilized synaptic transmission. Finally, blockade of the high-affinity proBDNF receptor p75(NTR) prevented the depression of asynchronously stimulated synapses. Thus, spontaneous activity drives local synaptic plasticity at individual synapses in an "out-of-sync, lose-your-link" fashion through proBDNF/p75(NTR) signaling to refine neuronal connectivity. VIDEO ABSTRACT.}, Author = {Winnubst, Johan and Cheyne, Juliette E and Niculescu, Dragos and Lohmann, Christian}, Date-Added = {2016-12-02 18:37:43 +0000}, Date-Modified = {2016-12-02 18:37:43 +0000}, Doi = {10.1016/j.neuron.2015.06.029}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Action Potentials; Animals; Animals, Newborn; Calcium; Computer Simulation; Electric Stimulation; Excitatory Amino Acid Antagonists; In Vitro Techniques; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Biological; Nerve Net; Neuronal Plasticity; Neurons; Organ Culture Techniques; Patch-Clamp Techniques; Quinoxalines; Signal Transduction; Visual Cortex}, Month = {Jul}, Number = {2}, Pages = {399-410}, pmid = {26182421}, Pst = {ppublish}, Title = {Spontaneous Activity Drives Local Synaptic Plasticity In Vivo}, Volume = {87}, Year = {2015}, url = {papers/Winnubst_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.06.029}} @article{Niculescu:2014, Abstract = {The presence of direct, cytoplasmatic, communication between neurons in the brain of vertebrates has been demonstrated a long time ago. These gap junctions have been characterized in many brain areas in terms of subunit composition, biophysical properties, neuronal connectivity patterns, and developmental regulation. Although interesting findings emerged, showing that different subunits are specifically regulated during development, or that excitatory and inhibitory neuronal networks exhibit various electrical connectivity patterns, gap junctions did not receive much further interest. Originally, it was believed that gap junctions represent simple passageways for electrical and biochemical coordination early in development. Today, we know that gap junction connectivity is tightly regulated, following independent developmental patterns for excitatory and inhibitory networks. Electrical connections are important for many specific functions of neurons, and are, for example, required for the development of neuronal stimulus tuning in the visual system. Here, we integrate the available data on neuronal connectivity and gap junction properties, as well as the most recent findings concerning the functional implications of electrical connections in the developing thalamus and neocortex.}, Author = {Niculescu, Dragos and Lohmann, Christian}, Date-Added = {2016-12-02 18:35:44 +0000}, Date-Modified = {2016-12-02 18:35:44 +0000}, Doi = {10.1093/cercor/bht175}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {connexin; electrical synapse; gap junctions; neocortex; thalamus}, Mesh = {Animals; Connexins; Gap Junctions; Neocortex; Nerve Net; Neurons; Thalamus}, Month = {Dec}, Number = {12}, Pages = {3097-106}, Pmc = {PMC4224240}, pmid = {23843439}, Pst = {ppublish}, Title = {Gap junctions in developing thalamic and neocortical neuronal networks}, Volume = {24}, Year = {2014}, url = {papers/Niculescu_CerebCortex2014.pdf}} @article{Lohmann:2014, Abstract = {The brain is programmed to drive behaviour by precisely wiring the appropriate neuronal circuits. Wiring and rewiring of neuronal circuits largely depends on the orchestrated changes in the strengths of synaptic contacts. Here, we review how the rules of synaptic plasticity change during development of the brain, from birth to independence. We focus on the changes that occur at the postsynaptic side of excitatory glutamatergic synapses in the rodent hippocampus and neocortex. First we summarize the current data on the structure of synapses and the developmental expression patterns of the key molecular players of synaptic plasticity, N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, as well as pivotal kinases (Ca(2+)/calmodulin-dependent protein kinase II, protein kinase A, protein kinase C) and phosphatases (PP1, PP2A, PP2B). In the second part we relate these findings to important characteristics of the emerging network. We argue that the concerted and gradual shifts in the usage of plasticity molecules comply with the changing need for (re)wiring neuronal circuits.}, Author = {Lohmann, Christian and Kessels, Helmut W}, Date-Added = {2016-12-02 18:35:00 +0000}, Date-Modified = {2016-12-02 18:35:00 +0000}, Doi = {10.1113/jphysiol.2012.235119}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Animals; Brain; Humans; N-Methylaspartate; Nerve Net; Neuronal Plasticity; Phosphoric Monoester Hydrolases; Protein Kinases; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid}, Month = {Jan}, Number = {1}, Pages = {13-31}, Pmc = {PMC3903349}, pmid = {24144877}, Pst = {ppublish}, Title = {The developmental stages of synaptic plasticity}, Volume = {592}, Year = {2014}, url = {papers/Lohmann_JPhysiol2014.pdf}} @article{Leighton:2016, Abstract = {In order to accurately process incoming sensory stimuli, neurons must be organized into functional networks, with both genetic and environmental factors influencing the precise arrangement of connections between cells. Teasing apart the relative contributions of molecular guidance cues, spontaneous activity and visual experience during this maturation is on-going. During development of the sensory system, the first, rough organization of connections is created by molecular factors. These connections are then modulated by the intrinsically generated activity of neurons, even before the senses have become operational. Spontaneous waves of depolarizations sweep across the nervous system, placing them in a prime position to strengthen correct connections and weaken others, shaping synapses into a useful network. A large body of work now support the idea that, rather than being a mere side-effect of the system, spontaneous activity actually contains information which readies the nervous system so that, as soon as the senses become active, sensory information can be utilized by the animal. An example is the neonatal mouse. As soon as the eyelids first open, neurons in the cortex respond to visual information without the animal having previously encountered structured sensory input (Cang et al., 2005b; Rochefort et al., 2011; Zhang et al., 2012; Ko et al., 2013). In vivo imaging techniques have advanced considerably, allowing observation of the natural activity in the brain of living animals down to the level of the individual synapse. New (opto)genetic methods make it possible to subtly modulate the spatio-temporal properties of activity, aiding our understanding of how these characteristics relate to the function of spontaneous activity. Such experiments have had a huge impact on our knowledge by permitting direct testing of ideas about the plasticity mechanisms at play in the intact system, opening up a provocative range of fresh questions. Here, we intend to outline the most recent descriptions of spontaneous activity patterns in rodent developing sensory areas, as well as the inferences we can make about the information content of those activity patterns and ideas about the plasticity rules that allow this activity to shape the young brain.}, Author = {Leighton, Alexandra H and Lohmann, Christian}, Date = {2016}, Date-Added = {2016-12-02 18:34:52 +0000}, Date-Modified = {2016-12-02 18:34:52 +0000}, Doi = {10.3389/fncir.2016.00071}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {auditory system development; developmental biology; plasticity mechanisms; spontaneous activity; synaptic plasticity; visual system development}, Pages = {71}, Pmc = {PMC5011135}, pmid = {27656131}, Pst = {epublish}, Title = {The Wiring of Developing Sensory Circuits-From Patterned Spontaneous Activity to Synaptic Plasticity Mechanisms}, Volume = {10}, Year = {2016}, url = {papers/Leighton_FrontNeuralCircuits2016.pdf}} @article{Ramamurthi:1988, Abstract = {After a survey of the anatomical and physiological basis of operative treatment of behaviour disorders by stereotactic lesions in the amygdala and the posterior medial hypothalamus the author describes his own experiences with 603 operations for control of conservatively untreatable aggressiveness. In 481 cases bilateral amygdalotomies and in 122 mostly secondary posteromedian hypothalamotomies have been performed. Initially excellent or moderate improvement was achieved in 76%. After a follow-up of more than three years this figure only slightly decreased to 70%. The group of patients who did not positively respond (30%) needs further study to discover the reasons for failure.}, Author = {Ramamurthi, B}, Date-Added = {2016-12-01 21:12:44 +0000}, Date-Modified = {2016-12-01 21:12:44 +0000}, Journal = {Acta Neurochir Suppl (Wien)}, Journal-Full = {Acta neurochirurgica. Supplementum}, Mesh = {Adolescent; Aggression; Amygdala; Attention Deficit Disorder with Hyperactivity; Child; Child Behavior Disorders; Epilepsy; Follow-Up Studies; Humans; Hypothalamus; Neurocognitive Disorders; Neuropsychological Tests; Postoperative Complications; Psychomotor Agitation; Stereotaxic Techniques; Violence}, Pages = {152-7}, pmid = {3066131}, Pst = {ppublish}, Title = {Stereotactic operation in behaviour disorders. Amygdalotomy and hypothalamotomy}, Volume = {44}, Year = {1988}} @article{Kano:2009, Abstract = {The discovery of cannabinoid receptors and subsequent identification of their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on cannabinoid actions in the brain. Then, the discovery in 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for cannabinoid research and also established a new concept how diffusible messengers modulate synaptic efficacy and neural activity. The last 7 years have witnessed remarkable advances in our understanding of the endocannabinoid system. It is now well accepted that endocannabinoids are released from postsynaptic neurons, activate presynaptic cannabinoid CB(1) receptors, and cause transient and long-lasting reduction of neurotransmitter release. In this review, we aim to integrate our current understanding of functions of the endocannabinoid system, especially focusing on the control of synaptic transmission in the brain. We summarize recent electrophysiological studies carried out on synapses of various brain regions and discuss how synaptic transmission is regulated by endocannabinoid signaling. Then we refer to recent anatomical studies on subcellular distribution of the molecules involved in endocannabinoid signaling and discuss how these signaling molecules are arranged around synapses. In addition, we make a brief overview of studies on cannabinoid receptors and their intracellular signaling, biochemical studies on endocannabinoid metabolism, and behavioral studies on the roles of the endocannabinoid system in various aspects of neural functions.}, Author = {Kano, Masanobu and Ohno-Shosaku, Takako and Hashimotodani, Yuki and Uchigashima, Motokazu and Watanabe, Masahiko}, Date-Added = {2016-11-15 20:43:47 +0000}, Date-Modified = {2016-11-15 20:43:47 +0000}, Doi = {10.1152/physrev.00019.2008}, Journal = {Physiol Rev}, Journal-Full = {Physiological reviews}, Mesh = {Animals; Cannabinoid Receptor Modulators; Endocannabinoids; Humans; Receptors, Cannabinoid; Signal Transduction; Synapses; Synaptic Transmission}, Month = {Jan}, Number = {1}, Pages = {309-80}, pmid = {19126760}, Pst = {ppublish}, Title = {Endocannabinoid-mediated control of synaptic transmission}, Volume = {89}, Year = {2009}, url = {papers/Kano_PhysiolRev2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/physrev.00019.2008}} @article{Berchtold:2000, Abstract = {Mammalian skeletal muscle shows an enormous variability in its functional features such as rate of force production, resistance to fatigue, and energy metabolism, with a wide spectrum from slow aerobic to fast anaerobic physiology. In addition, skeletal muscle exhibits high plasticity that is based on the potential of the muscle fibers to undergo changes of their cytoarchitecture and composition of specific muscle protein isoforms. Adaptive changes of the muscle fibers occur in response to a variety of stimuli such as, e.g., growth and differentition factors, hormones, nerve signals, or exercise. Additionally, the muscle fibers are arranged in compartments that often function as largely independent muscular subunits. All muscle fibers use Ca(2+) as their main regulatory and signaling molecule. Therefore, contractile properties of muscle fibers are dependent on the variable expression of proteins involved in Ca(2+) signaling and handling. Molecular diversity of the main proteins in the Ca(2+) signaling apparatus (the calcium cycle) largely determines the contraction and relaxation properties of a muscle fiber. The Ca(2+) signaling apparatus includes 1) the ryanodine receptor that is the sarcoplasmic reticulum Ca(2+) release channel, 2) the troponin protein complex that mediates the Ca(2+) effect to the myofibrillar structures leading to contraction, 3) the Ca(2+) pump responsible for Ca(2+) reuptake into the sarcoplasmic reticulum, and 4) calsequestrin, the Ca(2+) storage protein in the sarcoplasmic reticulum. In addition, a multitude of Ca(2+)-binding proteins is present in muscle tissue including parvalbumin, calmodulin, S100 proteins, annexins, sorcin, myosin light chains, beta-actinin, calcineurin, and calpain. These Ca(2+)-binding proteins may either exert an important role in Ca(2+)-triggered muscle contraction under certain conditions or modulate other muscle activities such as protein metabolism, differentiation, and growth. Recently, several Ca(2+) signaling and handling molecules have been shown to be altered in muscle diseases. Functional alterations of Ca(2+) handling seem to be responsible for the pathophysiological conditions seen in dystrophinopathies, Brody's disease, and malignant hyperthermia. These also underline the importance of the affected molecules for correct muscle performance.}, Author = {Berchtold, M W and Brinkmeier, H and M{\"u}ntener, M}, Date-Added = {2016-11-15 20:42:46 +0000}, Date-Modified = {2016-11-15 20:42:46 +0000}, Journal = {Physiol Rev}, Journal-Full = {Physiological reviews}, Mesh = {Animals; Calcium; Calcium Signaling; Calcium-Transporting ATPases; Humans; Muscle Fibers, Skeletal; Muscle, Skeletal; Troponin}, Month = {Jul}, Number = {3}, Pages = {1215-65}, pmid = {10893434}, Pst = {ppublish}, Title = {Calcium ion in skeletal muscle: its crucial role for muscle function, plasticity, and disease}, Volume = {80}, Year = {2000}, url = {papers/Berchtold_PhysiolRev2000.pdf}} @article{Tang:2014, Abstract = {Voltage-gated calcium (CaV) channels catalyse rapid, highly selective influx of Ca(2+) into cells despite a 70-fold higher extracellular concentration of Na(+). How CaV channels solve this fundamental biophysical problem remains unclear. Here we report physiological and crystallographic analyses of a calcium selectivity filter constructed in the homotetrameric bacterial NaV channel NaVAb. Our results reveal interactions of hydrated Ca(2+) with two high-affinity Ca(2+)-binding sites followed by a third lower-affinity site that would coordinate Ca(2+) as it moves inward. At the selectivity filter entry, Site 1 is formed by four carboxyl side chains, which have a critical role in determining Ca(2+) selectivity. Four carboxyls plus four backbone carbonyls form Site 2, which is targeted by the blocking cations Cd(2+) and Mn(2+), with single occupancy. The lower-affinity Site 3 is formed by four backbone carbonyls alone, which mediate exit into the central cavity. This pore architecture suggests a conduction pathway involving transitions between two main states with one or two hydrated Ca(2+) ions bound in the selectivity filter and supports a 'knock-off' mechanism of ion permeation through a stepwise-binding process. The multi-ion selectivity filter of our CaVAb model establishes a structural framework for understanding the mechanisms of ion selectivity and conductance by vertebrate CaV channels.}, Author = {Tang, Lin and Gamal El-Din, Tamer M and Payandeh, Jian and Martinez, Gilbert Q and Heard, Teresa M and Scheuer, Todd and Zheng, Ning and Catterall, William A}, Date-Added = {2016-10-20 21:29:41 +0000}, Date-Modified = {2016-10-20 21:29:41 +0000}, Doi = {10.1038/nature12775}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Bacterial Proteins; Binding Sites; Biocatalysis; Calcium; Calcium Channels; Cations, Divalent; Crystallography, X-Ray; Electric Conductivity; Ion Channel Gating; Models, Biological; Models, Molecular; Structure-Activity Relationship; Substrate Specificity}, Month = {Jan}, Number = {7481}, Pages = {56-61}, Pmc = {PMC3877713}, pmid = {24270805}, Pst = {ppublish}, Title = {Structural basis for Ca2+ selectivity of a voltage-gated calcium channel}, Volume = {505}, Year = {2014}, url = {papers/Tang_Nature2014.pdf}} @article{Davies:2003, Abstract = {Ethanol is a chemically simple compound that produces many well-known effects in humans. The prevailing idea for many years was that ethanol and other alcohols exerted their effects on the central nervous system (CNS) by non-selectively disrupting the lipid bilayers of neurons. However, in recent years, there has been an accumulation of evidence pointing to the importance of ligand-gated ion channels (LGICs) in mediating the effects of ethanol. Of these LGICs, gamma-aminobutyric acid type A (GABAA) receptors appear to occupy a central role in mediating the effects of ethanol in the CNS. GABA is the primary inhibitory neurotransmitter in the mammalian CNS, and activation of GABAA receptors by GABA tends to decrease neuronal excitability. This article reviews several aspects of GABAA receptor and ethanol interactions, including the evidence for short- and long-term modulation of GABAA receptors by ethanol and evidence for a GABAA receptor-related genetic component of alcoholism.}, Author = {Davies, Martin}, Date-Added = {2016-10-20 20:41:05 +0000}, Date-Modified = {2016-10-20 20:41:05 +0000}, Journal = {J Psychiatry Neurosci}, Journal-Full = {Journal of psychiatry \& neuroscience : JPN}, Mesh = {Alcoholism; Animals; Brain; Cell Membrane; Ethanol; Female; Fetal Alcohol Spectrum Disorders; Humans; Pregnancy; Receptors, GABA-A; Self Administration}, Month = {Jul}, Number = {4}, Pages = {263-74}, Pmc = {PMC165791}, pmid = {12921221}, Pst = {ppublish}, Title = {The role of GABAA receptors in mediating the effects of alcohol in the central nervous system}, Volume = {28}, Year = {2003}, url = {papers/Davies_JPsychiatryNeurosci2003.pdf}} @article{Mihic:1997, Abstract = {Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.}, Author = {Mihic, S J and Ye, Q and Wick, M J and Koltchine, V V and Krasowski, M D and Finn, S E and Mascia, M P and Valenzuela, C F and Hanson, K K and Greenblatt, E P and Harris, R A and Harrison, N L}, Date-Added = {2016-10-20 20:39:53 +0000}, Date-Modified = {2016-10-20 20:39:53 +0000}, Doi = {10.1038/38738}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Alanine; Amino Acid Sequence; Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Binding Sites; Cell Line; Electrophysiology; Enflurane; Ethanol; Glycine; Humans; Molecular Sequence Data; Mutagenesis; Propofol; Receptors, GABA-A; Receptors, Glycine; Recombinant Fusion Proteins; Sequence Homology, Amino Acid; Serine; Tryptophan; Xenopus}, Month = {Sep}, Number = {6649}, Pages = {385-9}, pmid = {9311780}, Pst = {ppublish}, Title = {Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors}, Volume = {389}, Year = {1997}, url = {papers/Mihic_Nature1997.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/38738}} @article{Picciotto:2000, Abstract = {Molecular cloning has elucidated the sequence of a family of acetylcholine receptor subunits that are activated by nicotine. Subsequent studies on the localization of individual subunits and the physiological properties of nicotinic subunit combinations in vitro, have led to identification of subunit compositions of nicotinic receptors that may function in vivo, as the native receptor. A particular challenge for the field has been to use these molecular data to determine which individual nicotinic receptor subtype is responsible for mediating each of the behavioral effects of nicotine. Human and animal studies have shown that nicotine is reinforcing and likely responsible for the addictive properties of tobacco. In addition, nicotine has been shown to have effects on locomotion, cognition, affect, and pain sensitivity. Recent studies combining the techniques of molecular biology, pharmacology, electrophysiology, and behavioral analysis to analyze knock out mice that lack individual subunits of the nicotinic acetylcholine receptor, have helped identify the role of specific nicotinic subunits in some of these complex behaviors. These studies could ultimately be useful in designing specific nicotinic receptor agonists and antagonists that may have uses in the clinic.}, Author = {Picciotto, M R and Caldarone, B J and King, S L and Zachariou, V}, Date-Added = {2016-10-20 20:37:26 +0000}, Date-Modified = {2016-10-20 20:37:26 +0000}, Doi = {10.1016/S0893-133X(99)00146-3}, Journal = {Neuropsychopharmacology}, Journal-Full = {Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology}, Mesh = {Animals; Behavior; Humans; Mice; Mice, Knockout; Models, Neurological; Molecular Biology; Receptors, Nicotinic}, Month = {May}, Number = {5}, Pages = {451-65}, pmid = {10731620}, Pst = {ppublish}, Title = {Nicotinic receptors in the brain. Links between molecular biology and behavior}, Volume = {22}, Year = {2000}, url = {papers/Picciotto_Neuropsychopharmacology2000.pdf}} @article{Chavas:2003, Abstract = {Functional GABA synapses are usually assumed to be inhibitory. However, we show here that inhibitory and excitatory GABA connections coexist in the cerebellar interneuron network. The reversal potential of GABAergic currents (E(GABA)) measured in interneurons is relatively depolarized and contrasts with the hyperpolarized value found in Purkinje cells (-58 and -85 mV respectively). This finding is not correlated to a specific developmental stage and is maintained in the adult animal. E(GABA) in interneurons is close to the mean membrane potential (-56.5 mV, as measured with a novel "equal firing potential" method), and both parameters vary enough among cells so that the driving force for GABA currents can be either inward or outward. Indeed, using noninvasive cell-attached recordings, we demonstrate inhibitory, excitatory, and sequential inhibitory and excitatory responses to interneuron stimulation [results obtained both in juvenile (postnatal days 12-14) and subadult (postnatal days 20-25) animals]. In hyperpolarized cells, single synaptic GABA currents can trigger spikes or trains of spikes, and subthreshold stimulations enhance the responsiveness to subsequent excitatory stimulation over at least 30 msec. We suggest that the coexistence of excitatory and inhibitory GABA synapses could either buffer the mean firing rate of the interneuron network or introduce different types of correlation between neighboring interneurons, or both.}, Author = {Chavas, Jo{\"e}l and Marty, Alain}, Date-Added = {2016-10-20 17:48:52 +0000}, Date-Modified = {2016-10-20 17:48:52 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Action Potentials; Age Factors; Animals; Cerebellum; Electric Stimulation; Excitatory Postsynaptic Potentials; Gramicidin; In Vitro Techniques; Interneurons; Membrane Potentials; Nerve Net; Neural Inhibition; Patch-Clamp Techniques; Potassium; Purkinje Cells; Rats; Receptors, GABA-A; Sodium; Synapses; gamma-Aminobutyric Acid}, Month = {Mar}, Number = {6}, Pages = {2019-31}, pmid = {12657660}, Pst = {ppublish}, Title = {Coexistence of excitatory and inhibitory GABA synapses in the cerebellar interneuron network}, Volume = {23}, Year = {2003}, url = {papers/Chavas_JNeurosci2003.pdf}} @article{Takeuchi:1960, Author = {Takeuchi, A and Takeuchi, N}, Date-Added = {2016-10-19 21:20:31 +0000}, Date-Modified = {2016-10-19 21:21:21 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {MYONEURAL JUNCTION/physiology}, Mesh = {Neuromuscular Junction; Permeability}, Month = {Nov}, Pages = {52-67}, Pmc = {PMC1359785}, pmid = {13774972}, Pst = {ppublish}, Title = {On the permeability of end-plate membrane during the action of transmitter}, Volume = {154}, Year = {1960}} @article{McPartland:2001, Abstract = {The endocannabinoid system exerts an important neuromodulatory role in mammals. Knockout mice lacking cannabinoid (CB) receptors exhibit significant morbidity. The endocannabinoid system also appears to be phylogenetically ancient--it occurs in mammals, birds, amphibians, fish, sea urchins, leeches, mussels, and even the most primitive animal with a nerve network, the Hydra. The presence of CB receptors, however, has not been examined in terrestrial invertebrates (or any member of the Ecdysozoa). Surprisingly, we found no specific binding of the synthetic CB ligands [(3)H]CP55,940 and [(3)H]SR141716A in a panel of insects: Apis mellifera, Drosophila melanogaster, Gerris marginatus, Spodoptera frugiperda, and Zophobas atratus. A lack of functional CB receptors was confirmed by the inability of tetrahydrocannabinol (THC) and HU210 to activate G-proteins in insect tissues, utilizing a guanosine-5'-O-(3-[(35)]thio)-triphosphate (GTP gamma S) assay. No orthologs of human CB receptors were located in the Drosophila genome, nor did we find orthologs of fatty acid amide hydrolase. This loss of CB receptors appears to be unique in the field of comparative neurobiology. No other known mammalian neuroreceptor is understood to be missing in insects. We hypothesized that CB receptors were lost in insects because of a dearth of ligands; endogenous CB ligands are metabolites of arachidonic acid, and insects produce little or no arachidonic acid or endocannabinoid ligands, such as anandamide.}, Author = {McPartland, J and Di Marzo, V and De Petrocellis, L and Mercer, A and Glass, M}, Date-Added = {2016-10-18 19:24:41 +0000}, Date-Modified = {2016-10-18 19:24:41 +0000}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Amino Acid Sequence; Animals; Bees; Beetles; Cannabinoid Receptor Modulators; Cats; Gas Chromatography-Mass Spectrometry; Humans; Insects; Ligands; Malpighian Tubules; Molecular Sequence Data; Rats; Receptors, Cannabinoid; Receptors, Drug}, Month = {Aug}, Number = {4}, Pages = {423-9}, pmid = {11447587}, Pst = {ppublish}, Title = {Cannabinoid receptors are absent in insects}, Volume = {436}, Year = {2001}} @article{Jeffries:2014, Abstract = {Long-chain fatty acid amides are cell-signaling lipids identified in mammals and, recently, in invertebrates, as well. Many details regarding fatty acid amide metabolism remain unclear. Herein, we demonstrate that Drosophila melanogaster is an excellent model system for the study long-chain fatty acid amide metabolism as we have quantified the endogenous levels of N-acylglycines, N-acyldopamines, N-acylethanolamines, and primary fatty acid amides by LC/QTOF-MS. Growth of D. melanogaster on media supplemented with [1-(13)C]-palmitate lead to a family of (13)C-palmitate-labeled fatty acid amides in the fly heads. The [1-(13)C]-palmitate feeding studies provide insight into the biosynthesis of the fatty acid amides.}, Author = {Jeffries, Kristen A and Dempsey, Daniel R and Behari, Anita L and Anderson, Ryan L and Merkler, David J}, Date-Added = {2016-10-18 19:24:02 +0000}, Date-Modified = {2016-10-18 19:24:02 +0000}, Doi = {10.1016/j.febslet.2014.02.051}, Journal = {FEBS Lett}, Journal-Full = {FEBS letters}, Keywords = {Biosynthetic pathway; Drosophila melanogaster; Endogenous quantification; Heavy-labeled precursor; Long-chain fatty acid amide; Model system}, Mesh = {Animals; Drosophila melanogaster; Ethanolamines; Lipid Metabolism; Palmitic Acids}, Month = {May}, Number = {9}, Pages = {1596-602}, Pmc = {PMC4023565}, pmid = {24650760}, Pst = {ppublish}, Title = {Drosophila melanogaster as a model system to study long-chain fatty acid amide metabolism}, Volume = {588}, Year = {2014}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.febslet.2014.02.051}} @article{Tomaso:1996, Author = {di Tomaso, E and Beltramo, M and Piomelli, D}, Date-Added = {2016-10-18 19:19:52 +0000}, Date-Modified = {2016-10-18 19:19:52 +0000}, Doi = {10.1038/382677a0}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Amidohydrolases; Animals; Arachidonic Acids; Brain Chemistry; Cacao; Candy; Cannabinoids; Cells, Cultured; Endocannabinoids; Ethanolamines; Gas Chromatography-Mass Spectrometry; Polyunsaturated Alkamides; Rats}, Month = {Aug}, Number = {6593}, Pages = {677-8}, pmid = {8751435}, Pst = {ppublish}, Title = {Brain cannabinoids in chocolate}, Volume = {382}, Year = {1996}, url = {papers/Tomaso_Nature1996.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/382677a0}} @article{Pacher:2006, Abstract = {The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB(1) receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB(1) receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB(2) receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients' need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy.}, Author = {Pacher, P{\'a}l and B{\'a}tkai, S{\'a}ndor and Kunos, George}, Date-Added = {2016-10-18 19:16:16 +0000}, Date-Modified = {2016-10-18 19:16:16 +0000}, Doi = {10.1124/pr.58.3.2}, Journal = {Pharmacol Rev}, Journal-Full = {Pharmacological reviews}, Mesh = {Animals; Cannabinoid Receptor Modulators; Endocannabinoids; Humans; Metabolic Diseases; Models, Biological}, Month = {Sep}, Number = {3}, Pages = {389-462}, Pmc = {PMC2241751}, pmid = {16968947}, Pst = {ppublish}, Title = {The endocannabinoid system as an emerging target of pharmacotherapy}, Volume = {58}, Year = {2006}, url = {papers/Pacher_PharmacolRev2006.pdf}} @article{Gertsch:2010, Abstract = {It is intriguing that during human cultural evolution man has detected plant natural products that appear to target key protein receptors of important physiological systems rather selectively. Plants containing such secondary metabolites usually belong to unique chemotaxa, induce potent pharmacological effects and have typically been used for recreational and medicinal purposes or as poisons. Cannabis sativa L. has a long history as a medicinal plant and was fundamental in the discovery of the endocannabinoid system. The major psychoactive Cannabis constituent Delta(9)-tetrahydrocannabinol (Delta(9)-THC) potently activates the G-protein-coupled cannabinoid receptor CB(1) and also modulates the cannabinoid receptor CB(2). In the last few years, several other non-cannabinoid plant constituents have been reported to bind to and functionally interact with CB receptors. Moreover, certain plant natural products, from both Cannabis and other plants, also target other proteins of the endocannabinoid system, such as hydrolytic enzymes that control endocannabinoid levels. In this commentary we summarize and critically discuss recent findings.}, Author = {Gertsch, J{\"u}rg and Pertwee, Roger G and Di Marzo, Vincenzo}, Date-Added = {2016-10-18 18:10:49 +0000}, Date-Modified = {2016-10-18 18:10:49 +0000}, Doi = {10.1111/j.1476-5381.2010.00745.x}, Journal = {Br J Pharmacol}, Journal-Full = {British journal of pharmacology}, Mesh = {Animals; Biological Products; Cannabinoids; Cannabis; Fatty Acids; Flavonoids; Humans; Molecular Structure; Phenols; Polyphenols; Receptors, Cannabinoid; Terpenes}, Month = {Jun}, Number = {3}, Pages = {523-9}, Pmc = {PMC2931553}, pmid = {20590562}, Pst = {ppublish}, Title = {Phytocannabinoids beyond the Cannabis plant - do they exist?}, Volume = {160}, Year = {2010}, url = {papers/Gertsch_BrJPharmacol2010.pdf}} @article{Singh:2013, Abstract = {Autism is a common and heritable neuropsychiatric disorder that can be categorized into two types: syndromic and nonsyndromic, the former of which are associated with other neurological disorders or syndromes. Molecular and functional links between syndromic and nonsyndromic autism genes were lacking until studies aimed at understanding the role of trans-synaptic adhesion molecule neuroligin, which is associated with nonsyndromic autism, provided important connections. Here, we integrate data from these studies into a model of how neuroligin functions to control synaptic connectivity in the central nervous system and how neuroligin dysfunction may participate in the pathophysiology of autism. Understanding the complex functional interactions between neuroligins and other autism-associated proteins at the synapse is crucial to understand the pathology of autism. This understanding might bring us closer to development of therapeutic approaches for autism.}, Author = {Singh, Sandeep K and Eroglu, Cagla}, Date-Added = {2016-08-04 15:10:18 +0000}, Date-Modified = {2016-08-04 15:15:08 +0000}, Doi = {10.1126/scisignal.2004102}, Journal = {Sci Signal}, Journal-Full = {Science signaling}, Keywords = {autism; Autistic Disorder; heritability}, Mesh = {Activated-Leukocyte Cell Adhesion Molecule; Animals; Autistic Disorder; Humans; Synapses; Synaptic Transmission; Syndrome}, Month = {Jul}, Number = {283}, Pages = {re4}, Pmc = {PMC4000534}, pmid = {23838185}, Pst = {epublish}, Title = {Neuroligins provide molecular links between syndromic and nonsyndromic autism}, Volume = {6}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/scisignal.2004102}} @article{Torre-Ubieta:2016, Abstract = {Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies.}, Author = {de la Torre-Ubieta, Luis and Won, Hyejung and Stein, Jason L and Geschwind, Daniel H}, Date-Added = {2016-08-04 14:41:44 +0000}, Date-Modified = {2016-08-04 14:41:44 +0000}, Doi = {10.1038/nm.4071}, Journal = {Nat Med}, Journal-Full = {Nature medicine}, Month = {Apr}, Number = {4}, Pages = {345-61}, pmid = {27050589}, Pst = {ppublish}, Title = {Advancing the understanding of autism disease mechanisms through genetics}, Volume = {22}, Year = {2016}, url = {papers/Torre-Ubieta_NatMed2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm.4071}} @article{Sandin:2014, Abstract = {IMPORTANCE: Autism spectrum disorder (ASD) aggregates in families, but the individual risk and to what extent this is caused by genetic factors or shared or nonshared environmental factors remains unresolved. OBJECTIVE: To provide estimates of familial aggregation and heritability of ASD. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort including 2,049,973 Swedish children born 1982 through 2006. We identified 37,570 twin pairs, 2,642,064 full sibling pairs, 432,281 maternal and 445,531 paternal half sibling pairs, and 5,799,875 cousin pairs. Diagnoses of ASD to December 31, 2009 were ascertained. MAIN OUTCOMES AND MEASURES: The relative recurrence risk (RRR) measures familial aggregation of disease. The RRR is the relative risk of autism in a participant with a sibling or cousin who has the diagnosis (exposed) compared with the risk in a participant with no diagnosed family member (unexposed). We calculated RRR for both ASD and autistic disorder adjusting for age, birth year, sex, parental psychiatric history, and parental age. We estimated how much of the probability of developing ASD can be related to genetic (additive and dominant) and environmental (shared and nonshared) factors. RESULTS: In the sample, 14,516 children were diagnosed with ASD, of whom 5689 had autistic disorder. The RRR and rate per 100,000 person-years for ASD among monozygotic twins was estimated to be 153.0 (95% CI, 56.7-412.8; rate, 6274 for exposed vs 27 for unexposed ); for dizygotic twins, 8.2 (95% CI, 3.7-18.1; rate, 805 for exposed vs 55 for unexposed); for full siblings, 10.3 (95% CI, 9.4-11.3; rate, 829 for exposed vs 49 for unexposed); for maternal half siblings, 3.3 (95% CI, 2.6-4.2; rate, 492 for exposed vs 94 for unexposed); for paternal half siblings, 2.9 (95% CI, 2.2-3.7; rate, 371 for exposed vs 85 for unexposed); and for cousins, 2.0 (95% CI, 1.8-2.2; rate, 155 for exposed vs 49 for unexposed). The RRR pattern was similar for autistic disorder but of slightly higher magnitude.We found support for a disease etiology including only additive genetic and nonshared environmental effects. The ASD heritability was estimated to be 0.50 (95% CI, 0.45-0.56) and the autistic disorder heritability was estimated to 0.54 (95% CI, 0.44-0.64). CONCLUSIONS AND RELEVANCE: Among children born in Sweden, the individual risk of ASD and autistic disorder increased with increasing genetic relatedness. Heritability of ASD and autistic disorder were estimated to be approximately 50%. These findings may inform the counseling of families with affected children.}, Author = {Sandin, Sven and Lichtenstein, Paul and Kuja-Halkola, Ralf and Larsson, Henrik and Hultman, Christina M and Reichenberg, Abraham}, Date-Added = {2016-08-04 14:22:15 +0000}, Date-Modified = {2016-08-04 14:22:15 +0000}, Doi = {10.1001/jama.2014.4144}, Journal = {JAMA}, Journal-Full = {JAMA}, Mesh = {Adolescent; Adult; Autistic Disorder; Child; Child, Preschool; Cohort Studies; Female; Genetic Predisposition to Disease; Humans; Male; Maternal Age; Paternal Age; Registries; Risk; Sweden; Twins, Monozygotic; Young Adult}, Month = {May}, Number = {17}, Pages = {1770-7}, Pmc = {PMC4381277}, pmid = {24794370}, Pst = {ppublish}, Title = {The familial risk of autism}, Volume = {311}, Year = {2014}, url = {papers/Sandin_JAMA2014a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1001/jama.2014.4144}} @article{Tan:2010, Abstract = {Recent genetic studies have implicated a number of candidate genes in the pathogenesis of Autism Spectrum Disorder (ASD). Polymorphisms of CNTNAP2 (contactin-associated like protein-2), a member of the neurexin family, have already been implicated as a susceptibility gene for autism by at least 3 separate studies. We investigated variation in white and grey matter morphology using structural MRI and diffusion tensor imaging. We compared volumetric differences in white and grey matter and fractional anisotropy values in control subjects characterised by genotype at rs7794745, a single nucleotide polymorphism in CNTNAP2. Homozygotes for the risk allele showed significant reductions in grey and white matter volume and fractional anisotropy in several regions that have already been implicated in ASD, including the cerebellum, fusiform gyrus, occipital and frontal cortices. Male homozygotes for the risk alleles showed greater reductions in grey matter in the right frontal pole and in FA in the right rostral fronto-occipital fasciculus compared to their female counterparts who showed greater reductions in FA of the anterior thalamic radiation. Thus a risk allele for autism results in significant cerebral morphological variation, despite the absence of overt symptoms or behavioural abnormalities. The results are consistent with accumulating evidence of CNTNAP2's function in neuronal development. The finding suggests the possibility that the heterogeneous manifestations of ASD can be aetiologically characterised into distinct subtypes through genetic-morphological analysis.}, Author = {Tan, Geoffrey C Y and Doke, Thomas F and Ashburner, John and Wood, Nicholas W and Frackowiak, Richard S J}, Date-Added = {2016-08-04 00:17:26 +0000}, Date-Modified = {2016-08-04 00:17:26 +0000}, Doi = {10.1016/j.neuroimage.2010.02.018}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Mesh = {Anisotropy; Cerebellum; Child; Child Development Disorders, Pervasive; Endophenotypes; Female; Frontal Lobe; Genetic Predisposition to Disease; Genotype; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Membrane Proteins; Nerve Tissue Proteins; Neural Pathways; Occipital Lobe; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide}, Month = {Nov}, Number = {3}, Pages = {1030-42}, Pmc = {PMC2941042}, pmid = {20176116}, Pst = {ppublish}, Title = {Normal variation in fronto-occipital circuitry and cerebellar structure with an autism-associated polymorphism of CNTNAP2}, Volume = {53}, Year = {2010}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2010.02.018}} @article{Abrahams:2007, Abstract = {Despite the well established role of the frontal and posterior perisylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in the human brain. We performed a genome-wide analysis of human cerebral patterning during midgestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed between superior temporal gyrus (STG) and the remaining cerebral cortex. Gene ontology categories representing transcription factors were enriched in STG, whereas cell-adhesion and extracellular matrix molecules were enriched in the other cortical regions. Quantitative RT-PCR or in situ hybridization was performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain-binding 1 (LDB1), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 (LMO4), a gene known to be involved in the asymmetric pattering of the perisylvian region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin associated protein-like 2 (CNTNAP2), in which mutations are known to cause autism, epilepsy, and language delay, showed a remarkable pattern of anterior-enriched cortical expression in human that was not observed in mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and the disorders that disrupt them.}, Author = {Abrahams, B S and Tentler, D and Perederiy, J V and Oldham, M C and Coppola, G and Geschwind, D H}, Date-Added = {2016-08-04 00:16:17 +0000}, Date-Modified = {2016-08-04 00:16:17 +0000}, Doi = {10.1073/pnas.0706128104}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Cerebral Cortex; Cognition; Female; Gene Expression Regulation, Developmental; Genome, Human; Humans; Knowledge; Oligonucleotide Array Sequence Analysis; Pregnancy; Pregnancy Trimester, Second; Reverse Transcriptase Polymerase Chain Reaction}, Month = {Nov}, Number = {45}, Pages = {17849-54}, Pmc = {PMC2077018}, pmid = {17978184}, Pst = {ppublish}, Title = {Genome-wide analyses of human perisylvian cerebral cortical patterning}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0706128104}} @article{Scott-Van-Zeeland:2010, Abstract = {Genetic studies are rapidly identifying variants that shape risk for disorders of human cognition, but the question of how such variants predispose to neuropsychiatric disease remains. Noninvasive human brain imaging allows assessment of the brain in vivo, and the combination of genetics and imaging phenotypes remains one of the only ways to explore functional genotype-phenotype associations in human brain. Common variants in contactin-associated protein-like 2 (CNTNAP2), a neurexin superfamily member, have been associated with several allied neurodevelopmental disorders, including autism and specific language impairment, and CNTNAP2 is highly expressed in frontal lobe circuits in the developing human brain. Using functional neuroimaging, we have demonstrated a relationship between frontal lobar connectivity and common genetic variants in CNTNAP2. These data provide a mechanistic link between specific genetic risk for neurodevelopmental disorders and empirical data implicating dysfunction of long-range connections within the frontal lobe in autism. The convergence between genetic findings and cognitive-behavioral models of autism provides evidence that genetic variation at CNTNAP2 predisposes to diseases such as autism in part through modulation of frontal lobe connectivity.}, Author = {Scott-Van Zeeland, Ashley A and Abrahams, Brett S and Alvarez-Retuerto, Ana I and Sonnenblick, Lisa I and Rudie, Jeffrey D and Ghahremani, Dara and Mumford, Jeanette A and Poldrack, Russell A and Dapretto, Mirella and Geschwind, Daniel H and Bookheimer, Susan Y}, Date-Added = {2016-08-04 00:12:55 +0000}, Date-Modified = {2016-08-04 00:12:55 +0000}, Doi = {10.1126/scitranslmed.3001344}, Journal = {Sci Transl Med}, Journal-Full = {Science translational medicine}, Mesh = {Autistic Disorder; Frontal Lobe; Genetic Predisposition to Disease; Humans; Magnetic Resonance Imaging; Membrane Proteins; Nerve Tissue Proteins; Neural Pathways; Risk Factors}, Month = {Nov}, Number = {56}, Pages = {56ra80}, Pmc = {PMC3065863}, pmid = {21048216}, Pst = {ppublish}, Title = {Altered functional connectivity in frontal lobe circuits is associated with variation in the autism risk gene CNTNAP2}, Volume = {2}, Year = {2010}, url = {papers/Scott-VanZeeland_SciTranslMed2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/scitranslmed.3001344}} @article{Lu:2015, Author = {Lu, Ju and Zuo, Yi}, Date-Added = {2016-08-03 16:50:13 +0000}, Date-Modified = {2016-08-03 16:50:13 +0000}, Doi = {10.1038/nature15211}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Male; Memory; Motor Cortex; Neuronal Plasticity; Synapses}, Month = {Sep}, Number = {7569}, Pages = {324-5}, pmid = {26352474}, Pst = {ppublish}, Title = {Neuroscience: Forgetfulness illuminated}, Volume = {525}, Year = {2015}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature15211}} @article{Xu:2009, Abstract = {Novel motor skills are learned through repetitive practice and, once acquired, persist long after training stops. Earlier studies have shown that such learning induces an increase in the efficacy of synapses in the primary motor cortex, the persistence of which is associated with retention of the task. However, how motor learning affects neuronal circuitry at the level of individual synapses and how long-lasting memory is structurally encoded in the intact brain remain unknown. Here we show that synaptic connections in the living mouse brain rapidly respond to motor-skill learning and permanently rewire. Training in a forelimb reaching task leads to rapid (within an hour) formation of postsynaptic dendritic spines on the output pyramidal neurons in the contralateral motor cortex. Although selective elimination of spines that existed before training gradually returns the overall spine density back to the original level, the new spines induced during learning are preferentially stabilized during subsequent training and endure long after training stops. Furthermore, we show that different motor skills are encoded by different sets of synapses. Practice of novel, but not previously learned, tasks further promotes dendritic spine formation in adulthood. Our findings reveal that rapid, but long-lasting, synaptic reorganization is closely associated with motor learning. The data also suggest that stabilized neuronal connections are the foundation of durable motor memory.}, Author = {Xu, Tonghui and Yu, Xinzhu and Perlik, Andrew J and Tobin, Willie F and Zweig, Jonathan A and Tennant, Kelly and Jones, Theresa and Zuo, Yi}, Date-Added = {2016-08-03 16:50:01 +0000}, Date-Modified = {2016-08-03 16:50:01 +0000}, Doi = {10.1038/nature08389}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Aging; Animals; Dendrites; Forelimb; Memory; Mice; Motor Cortex; Motor Skills; Neuronal Plasticity; Psychomotor Performance; Pyramidal Cells; Seeds; Synapses; Time Factors}, Month = {Dec}, Number = {7275}, Pages = {915-9}, Pmc = {PMC2844762}, pmid = {19946267}, Pst = {ppublish}, Title = {Rapid formation and selective stabilization of synapses for enduring motor memories}, Volume = {462}, Year = {2009}, url = {papers/Xu_Nature2009.pdf}, Bdsk-File-2 = {papers/Xu_Nature2009a.pdf}, Bdsk-File-3 = {papers/Xu_Nature2009.mov}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08389}} @article{Fu:2012, Abstract = {Many lines of evidence suggest that memory in the mammalian brain is stored with distinct spatiotemporal patterns. Despite recent progresses in identifying neuronal populations involved in memory coding, the synapse-level mechanism is still poorly understood. Computational models and electrophysiological data have shown that functional clustering of synapses along dendritic branches leads to nonlinear summation of synaptic inputs and greatly expands the computing power of a neural network. However, whether neighbouring synapses are involved in encoding similar memory and how task-specific cortical networks develop during learning remain elusive. Using transcranial two-photon microscopy, we followed apical dendrites of layer 5 pyramidal neurons in the motor cortex while mice practised novel forelimb skills. Here we show that a third of new dendritic spines (postsynaptic structures of most excitatory synapses) formed during the acquisition phase of learning emerge in clusters, and that most such clusters are neighbouring spine pairs. These clustered new spines are more likely to persist throughout prolonged learning sessions, and even long after training stops, than non-clustered counterparts. Moreover, formation of new spine clusters requires repetition of the same motor task, and the emergence of succedent new spine(s) accompanies the strengthening of the first new spine in the cluster. We also show that under control conditions new spines appear to avoid existing stable spines, rather than being uniformly added along dendrites. However, succedent new spines in clusters overcome such a spatial constraint and form in close vicinity to neighbouring stable spines. Our findings suggest that clustering of new synapses along dendrites is induced by repetitive activation of the cortical circuitry during learning, providing a structural basis for spatial coding of motor memory in the mammalian brain.}, Author = {Fu, Min and Yu, Xinzhu and Lu, Ju and Zuo, Yi}, Date-Added = {2016-08-03 16:49:59 +0000}, Date-Modified = {2016-08-03 16:49:59 +0000}, Doi = {10.1038/nature10844}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Dendritic Spines; Forelimb; Learning; Mice; Models, Neurological; Motor Cortex; Psychomotor Performance; Pyramidal Cells; Synapses}, Month = {Mar}, Number = {7387}, Pages = {92-5}, Pmc = {PMC3292711}, pmid = {22343892}, Pst = {epublish}, Title = {Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo}, Volume = {483}, Year = {2012}, url = {papers/Fu_Nature2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature10844}} @article{Ho:2011, Abstract = {Estimation of demographic history from nucleotide sequences represents an important component of many studies in molecular ecology. For example, knowledge of a population's history can allow us to test hypotheses about the impact of climatic and anthropogenic factors. In the past, demographic analysis was typically limited to relatively simple population models, such as exponential or logistic growth. More flexible approaches are now available, including skyline-plot methods that are able to reconstruct changes in population sizes through time. This technical review focuses on these skyline-plot methods. We describe some general principles relating to sampling design and data collection. We then provide an outline of the methodological framework, which is based on coalescent theory, before tracing the development of the various skyline-plot methods and describing their key features. The performance and properties of the methods are illustrated using two simulated data sets.}, Author = {Ho, Simon Y W and Shapiro, Beth}, Date-Added = {2016-07-07 22:53:08 +0000}, Date-Modified = {2016-07-07 22:53:08 +0000}, Doi = {10.1111/j.1755-0998.2011.02988.x}, Journal = {Mol Ecol Resour}, Journal-Full = {Molecular ecology resources}, Mesh = {Demography; Genetics, Population; Humans; Models, Genetic; Sequence Analysis, DNA; Statistics as Topic}, Month = {May}, Number = {3}, Pages = {423-34}, pmid = {21481200}, Pst = {ppublish}, Title = {Skyline-plot methods for estimating demographic history from nucleotide sequences}, Volume = {11}, Year = {2011}, url = {papers/Ho_MolEcolResour2011.pdf}} @article{Green:2010, Abstract = {Neandertals, the closest evolutionary relatives of present-day humans, lived in large parts of Europe and western Asia before disappearing 30,000 years ago. We present a draft sequence of the Neandertal genome composed of more than 4 billion nucleotides from three individuals. Comparisons of the Neandertal genome to the genomes of five present-day humans from different parts of the world identify a number of genomic regions that may have been affected by positive selection in ancestral modern humans, including genes involved in metabolism and in cognitive and skeletal development. We show that Neandertals shared more genetic variants with present-day humans in Eurasia than with present-day humans in sub-Saharan Africa, suggesting that gene flow from Neandertals into the ancestors of non-Africans occurred before the divergence of Eurasian groups from each other.}, Author = {Green, Richard E and Krause, Johannes and Briggs, Adrian W and Maricic, Tomislav and Stenzel, Udo and Kircher, Martin and Patterson, Nick and Li, Heng and Zhai, Weiwei and Fritz, Markus Hsi-Yang and Hansen, Nancy F and Durand, Eric Y and Malaspinas, Anna-Sapfo and Jensen, Jeffrey D and Marques-Bonet, Tomas and Alkan, Can and Pr{\"u}fer, Kay and Meyer, Matthias and Burbano, Hern{\'a}n A and Good, Jeffrey M and Schultz, Rigo and Aximu-Petri, Ayinuer and Butthof, Anne and H{\"o}ber, Barbara and H{\"o}ffner, Barbara and Siegemund, Madlen and Weihmann, Antje and Nusbaum, Chad and Lander, Eric S and Russ, Carsten and Novod, Nathaniel and Affourtit, Jason and Egholm, Michael and Verna, Christine and Rudan, Pavao and Brajkovic, Dejana and Kucan, Zeljko and Gusic, Ivan and Doronichev, Vladimir B and Golovanova, Liubov V and Lalueza-Fox, Carles and de la Rasilla, Marco and Fortea, Javier and Rosas, Antonio and Schmitz, Ralf W and Johnson, Philip L F and Eichler, Evan E and Falush, Daniel and Birney, Ewan and Mullikin, James C and Slatkin, Montgomery and Nielsen, Rasmus and Kelso, Janet and Lachmann, Michael and Reich, David and P{\"a}{\"a}bo, Svante}, Date-Added = {2016-07-07 22:53:02 +0000}, Date-Modified = {2016-07-07 22:53:02 +0000}, Doi = {10.1126/science.1188021}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {African Continental Ancestry Group; Animals; Asian Continental Ancestry Group; Base Sequence; Bone and Bones; DNA, Mitochondrial; European Continental Ancestry Group; Evolution, Molecular; Extinction, Biological; Female; Fossils; Gene Dosage; Gene Flow; Genetic Variation; Genome; Genome, Human; Haplotypes; Hominidae; Humans; Pan troglodytes; Polymorphism, Single Nucleotide; Selection, Genetic; Sequence Alignment; Sequence Analysis, DNA; Time}, Month = {May}, Number = {5979}, Pages = {710-22}, pmid = {20448178}, Pst = {ppublish}, Title = {A draft sequence of the Neandertal genome}, Volume = {328}, Year = {2010}, url = {papers/Green_Science2010.pdf}} @article{Carninci:2005, Abstract = {This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.}, Author = {Carninci, P and Kasukawa, T and Katayama, S and Gough, J and Frith, M C and Maeda, N and Oyama, R and Ravasi, T and Lenhard, B and Wells, C and Kodzius, R and Shimokawa, K and Bajic, V B and Brenner, S E and Batalov, S and Forrest, A R R and Zavolan, M and Davis, M J and Wilming, L G and Aidinis, V and Allen, J E and Ambesi-Impiombato, A and Apweiler, R and Aturaliya, R N and Bailey, T L and Bansal, M and Baxter, L and Beisel, K W and Bersano, T and Bono, H and Chalk, A M and Chiu, K P and Choudhary, V and Christoffels, A and Clutterbuck, D R and Crowe, M L and Dalla, E and Dalrymple, B P and de Bono, B and Della Gatta, G and di Bernardo, D and Down, T and Engstrom, P and Fagiolini, M and Faulkner, G and Fletcher, C F and Fukushima, T and Furuno, M and Futaki, S and Gariboldi, M and Georgii-Hemming, P and Gingeras, T R and Gojobori, T and Green, R E and Gustincich, S and Harbers, M and Hayashi, Y and Hensch, T K and Hirokawa, N and Hill, D and Huminiecki, L and Iacono, M and Ikeo, K and Iwama, A and Ishikawa, T and Jakt, M and Kanapin, A and Katoh, M and Kawasawa, Y and Kelso, J and Kitamura, H and Kitano, H and Kollias, G and Krishnan, S P T and Kruger, A and Kummerfeld, S K and Kurochkin, I V and Lareau, L F and Lazarevic, D and Lipovich, L and Liu, J and Liuni, S and McWilliam, S and Madan Babu, M and Madera, M and Marchionni, L and Matsuda, H and Matsuzawa, S and Miki, H and Mignone, F and Miyake, S and Morris, K and Mottagui-Tabar, S and Mulder, N and Nakano, N and Nakauchi, H and Ng, P and Nilsson, R and Nishiguchi, S and Nishikawa, S and Nori, F and Ohara, O and Okazaki, Y and Orlando, V and Pang, K C and Pavan, W J and Pavesi, G and Pesole, G and Petrovsky, N and Piazza, S and Reed, J and Reid, J F and Ring, B Z and Ringwald, M and Rost, B and Ruan, Y and Salzberg, S L and Sandelin, A and Schneider, C and Sch{\"o}nbach, C and Sekiguchi, K and Semple, C A M and Seno, S and Sessa, L and Sheng, Y and Shibata, Y and Shimada, H and Shimada, K and Silva, D and Sinclair, B and Sperling, S and Stupka, E and Sugiura, K and Sultana, R and Takenaka, Y and Taki, K and Tammoja, K and Tan, S L and Tang, S and Taylor, M S and Tegner, J and Teichmann, S A and Ueda, H R and van Nimwegen, E and Verardo, R and Wei, C L and Yagi, K and Yamanishi, H and Zabarovsky, E and Zhu, S and Zimmer, A and Hide, W and Bult, C and Grimmond, S M and Teasdale, R D and Liu, E T and Brusic, V and Quackenbush, J and Wahlestedt, C and Mattick, J S and Hume, D A and Kai, C and Sasaki, D and Tomaru, Y and Fukuda, S and Kanamori-Katayama, M and Suzuki, M and Aoki, J and Arakawa, T and Iida, J and Imamura, K and Itoh, M and Kato, T and Kawaji, H and Kawagashira, N and Kawashima, T and Kojima, M and Kondo, S and Konno, H and Nakano, K and Ninomiya, N and Nishio, T and Okada, M and Plessy, C and Shibata, K and Shiraki, T and Suzuki, S and Tagami, M and Waki, K and Watahiki, A and Okamura-Oho, Y and Suzuki, H and Kawai, J and Hayashizaki, Y and {FANTOM Consortium} and {RIKEN Genome Exploration Research Group and Genome Science Group (Genome Network Project Core Group)}}, Date-Added = {2016-07-07 22:52:56 +0000}, Date-Modified = {2016-07-07 22:52:56 +0000}, Doi = {10.1126/science.1112014}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {3' Untranslated Regions; Animals; Base Sequence; Conserved Sequence; DNA, Complementary; Genome; Genome, Human; Genomics; Humans; Mice; Promoter Regions, Genetic; Proteins; RNA; RNA Splicing; RNA, Untranslated; Regulatory Sequences, Ribonucleic Acid; Terminator Regions, Genetic; Transcription Initiation Site; Transcription, Genetic}, Month = {Sep}, Number = {5740}, Pages = {1559-63}, pmid = {16141072}, Pst = {ppublish}, Title = {The transcriptional landscape of the mammalian genome}, Volume = {309}, Year = {2005}, url = {papers/Carninci_Science2005.pdf}} @article{Shapiro:2002, Author = {Shapiro, Beth and Sibthorpe, Dean and Rambaut, Andrew and Austin, Jeremy and Wragg, Graham M and Bininda-Emonds, Olaf R P and Lee, Patricia L M and Cooper, Alan}, Date-Added = {2016-07-07 22:52:33 +0000}, Date-Modified = {2016-07-07 22:52:33 +0000}, Doi = {10.1126/science.295.5560.1683}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Animals; Biological Evolution; Birds; Columbidae; DNA, Mitochondrial; Flight, Animal; Likelihood Functions; Phylogeny}, Month = {Mar}, Number = {5560}, Pages = {1683}, pmid = {11872833}, Pst = {ppublish}, Title = {Flight of the dodo}, Volume = {295}, Year = {2002}, url = {papers/Shapiro_Science2002.pdf}} @article{Eklund:2016, Abstract = {The most widely used task functional magnetic resonance imaging (fMRI) analyses use parametric statistical methods that depend on a variety of assumptions. In this work, we use real resting-state data and a total of 3 million random task group analyses to compute empirical familywise error rates for the fMRI software packages SPM, FSL, and AFNI, as well as a nonparametric permutation method. For a nominal familywise error rate of 5%, the parametric statistical methods are shown to be conservative for voxelwise inference and invalid for clusterwise inference. Our results suggest that the principal cause of the invalid cluster inferences is spatial autocorrelation functions that do not follow the assumed Gaussian shape. By comparison, the nonparametric permutation test is found to produce nominal results for voxelwise as well as clusterwise inference. These findings speak to the need of validating the statistical methods being used in the field of neuroimaging.}, Author = {Eklund, Anders and Nichols, Thomas E and Knutsson, Hans}, Date-Added = {2016-07-07 22:51:33 +0000}, Date-Modified = {2016-07-07 22:51:33 +0000}, Doi = {10.1073/pnas.1602413113}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {cluster inference; fMRI; false positives; permutation test; statistics}, Month = {Jun}, pmid = {27357684}, Pst = {aheadofprint}, Title = {Cluster failure: Why fMRI inferences for spatial extent have inflated false-positive rates}, Year = {2016}, url = {papers/Eklund_ProcNatlAcadSciUSA2016.pdf}} @article{Drummond:2005, Abstract = {We introduce the Bayesian skyline plot, a new method for estimating past population dynamics through time from a sample of molecular sequences without dependence on a prespecified parametric model of demographic history. We describe a Markov chain Monte Carlo sampling procedure that efficiently samples a variant of the generalized skyline plot, given sequence data, and combines these plots to generate a posterior distribution of effective population size through time. We apply the Bayesian skyline plot to simulated data sets and show that it correctly reconstructs demographic history under canonical scenarios. Finally, we compare the Bayesian skyline plot model to previous coalescent approaches by analyzing two real data sets (hepatitis C virus in Egypt and mitochondrial DNA of Beringian bison) that have been previously investigated using alternative coalescent methods. In the bison analysis, we detect a severe but previously unrecognized bottleneck, estimated to have occurred 10,000 radiocarbon years ago, which coincides with both the earliest undisputed record of large numbers of humans in Alaska and the megafaunal extinctions in North America at the beginning of the Holocene.}, Author = {Drummond, A J and Rambaut, A and Shapiro, B and Pybus, O G}, Date-Added = {2016-07-07 22:51:03 +0000}, Date-Modified = {2016-07-07 22:51:03 +0000}, Doi = {10.1093/molbev/msi103}, Journal = {Mol Biol Evol}, Journal-Full = {Molecular biology and evolution}, Mesh = {Algorithms; Animals; Bayes Theorem; Bison; DNA, Mitochondrial; Egypt; Evolution, Molecular; Genetics, Population; Hepacivirus; Hepatitis C; Humans; Markov Chains; Models, Genetic; Monte Carlo Method; Population Density; Population Dynamics; Time Factors}, Month = {May}, Number = {5}, Pages = {1185-92}, pmid = {15703244}, Pst = {ppublish}, Title = {Bayesian coalescent inference of past population dynamics from molecular sequences}, Volume = {22}, Year = {2005}, url = {papers/Drummond_MolBiolEvol2005.pdf}} @article{Kirkby:2013, Abstract = {Correlated spontaneous activity in the developing nervous system is robust to perturbations in the circuits that generate it, suggesting that mechanisms exist to ensure its maintenance. We examine this phenomenon in the developing retina, where blockade of cholinergic circuits that mediate retinal waves during the first postnatal week leads to the generation of "recovered" waves through a distinct, gap junction-mediated circuit. Unlike cholinergic waves, these recovered waves were modulated by dopaminergic and glutamatergic signaling, and required the presence of the gap junction protein connexin 36. Moreover, in contrast to cholinergic waves, recovered waves were stimulated by ambient light via activation of melanopsin-expressing intrinsically photosensitive retinal ganglion cells. The involvement of intrinsically photosensitive retinal ganglion cells in this reconfiguration of wave-generating circuits offers an avenue of retinal circuit plasticity during development that was previously unknown.}, Author = {Kirkby, Lowry A and Feller, Marla B}, Date-Added = {2016-07-07 17:34:20 +0000}, Date-Modified = {2016-07-07 17:34:20 +0000}, Doi = {10.1073/pnas.1222150110}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {degenerate circuit; dopamine; retinal development}, Mesh = {Animals; Connexins; Electrophysiological Processes; Gap Junctions; Light Signal Transduction; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Interference; Retina; Retinal Ganglion Cells; Rod Opsins; Synaptic Transmission}, Month = {Jul}, Number = {29}, Pages = {12090-5}, Pmc = {PMC3718101}, pmid = {23821744}, Pst = {ppublish}, Title = {Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits}, Volume = {110}, Year = {2013}, url = {papers/Kirkby_ProcNatlAcadSciUSA2013.pdf}} @article{Smith:2015, Abstract = {Stimulus discrimination depends on the selectivity and variability of neural responses, as well as the size and correlation structure of the responsive population. For direction discrimination in visual cortex, only the selectivity of neurons has been well characterized across development. Here we show in ferrets that at eye opening, the cortical response to visual stimulation exhibits several immaturities, including a high density of active neurons that display prominent wave-like activity, a high degree of variability and strong noise correlations. Over the next three weeks, the population response becomes increasingly sparse, wave-like activity disappears, and variability and noise correlations are markedly reduced. Similar changes were observed in identified neuronal populations imaged repeatedly over days. Furthermore, experience with a moving stimulus was capable of driving a reduction in noise correlations over a matter of hours. These changes in variability and correlation contribute significantly to a marked improvement in direction discriminability over development.}, Author = {Smith, Gordon B and Sederberg, Audrey and Elyada, Yishai M and Van Hooser, Stephen D and Kaschube, Matthias and Fitzpatrick, David}, Date-Added = {2016-07-07 17:19:04 +0000}, Date-Modified = {2016-07-07 17:19:04 +0000}, Doi = {10.1038/nn.3921}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Age Factors; Animals; Discrimination (Psychology); Female; Ferrets; Motion Perception; Nerve Net; Neurons; Optical Imaging; Visual Cortex}, Month = {Feb}, Number = {2}, Pages = {252-61}, Pmc = {PMC4334116}, pmid = {25599224}, Pst = {ppublish}, Title = {The development of cortical circuits for motion discrimination}, Volume = {18}, Year = {2015}, url = {papers/Smith_NatNeurosci2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.3921}} @article{McCormick:2015, Abstract = {Cortical and thalamocortical activity is highly state dependent, varying between patterns that are conducive to accurate sensory-motor processing, to states in which the brain is largely off-line and generating internal rhythms irrespective of the outside world. The generation of rhythmic activity occurs through the interaction of stereotyped patterns of connectivity together with intrinsic membrane and synaptic properties. One common theme in the generation of rhythms is the interaction of a positive feedback loop (e.g., recurrent excitation) with negative feedback control (e.g., inhibition, adaptation, or synaptic depression). The operation of these state-dependent activities has wide ranging effects from enhancing or blocking sensory-motor processing to the generation of pathological rhythms associated with psychiatric or neurological disorders.}, Author = {McCormick, David A and McGinley, Matthew J and Salkoff, David B}, Date-Added = {2016-07-06 23:27:49 +0000}, Date-Modified = {2016-07-06 23:27:49 +0000}, Doi = {10.1016/j.conb.2014.10.003}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Mesh = {Action Potentials; Animals; Cerebral Cortex; Feedback, Physiological; Humans; Models, Neurological; Neural Pathways; Periodicity; Thalamus}, Month = {Apr}, Pages = {133-40}, Pmc = {PMC4375098}, pmid = {25460069}, Pst = {ppublish}, Title = {Brain state dependent activity in the cortex and thalamus}, Volume = {31}, Year = {2015}, url = {papers/McCormick_CurrOpinNeurobiol2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2014.10.003}} @article{McCormick:2014, Author = {McCormick, David A and Nusbaum, Michael P}, Date-Added = {2016-07-06 23:27:48 +0000}, Date-Modified = {2016-07-06 23:27:48 +0000}, Doi = {10.1016/j.conb.2014.10.010}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Mesh = {Animals; Behavior; Humans; Nerve Net; Neurons; Neurotransmitter Agents}, Month = {Dec}, Pages = {iv-vii}, Pmc = {PMC4450677}, pmid = {25457725}, Pst = {ppublish}, Title = {Editorial overview: neuromodulation: tuning the properties of neurons, networks and behavior}, Volume = {29}, Year = {2014}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2014.10.010}} @article{Zagha:2014, Abstract = {How the brain takes in information, makes a decision, and acts on this decision is strongly influenced by the ongoing and constant fluctuations of state. Understanding the nature of these brain states and how they are controlled is critical to making sense of how the nervous system operates, both normally and abnormally. While broadly projecting neuromodulatory systems acting through metabotropic pathways have long been appreciated to be critical for determining brain state, more recent investigations have revealed a prominent role for fast acting neurotransmitter pathways for temporally and spatially precise control of neural processing. Corticocortical and thalamocortical glutamatergic projections can rapidly and precisely control brain state by changing both the nature of ongoing activity and by controlling the gain and precision of neural responses.}, Author = {Zagha, Edward and McCormick, David A}, Date-Added = {2016-07-06 23:27:46 +0000}, Date-Modified = {2016-07-06 23:27:46 +0000}, Doi = {10.1016/j.conb.2014.09.010}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Mesh = {Animals; Brain; Humans; Neural Pathways; Neurons}, Month = {Dec}, Pages = {178-86}, Pmc = {PMC4254046}, pmid = {25310628}, Pst = {ppublish}, Title = {Neural control of brain state}, Volume = {29}, Year = {2014}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2014.09.010}} @article{McGinley:2015a, Abstract = {The state of the brain and body constantly varies on rapid and slow timescales. These variations contribute to the apparent noisiness of sensory responses at both the neural and the behavioral level. Recent investigations of rapid state changes in awake, behaving animals have provided insight into the mechanisms by which optimal sensory encoding and behavioral performance are achieved. Fluctuations in state, as indexed by pupillometry, impact both the "signal" (sensory evoked response) and the "noise" (spontaneous activity) of cortical responses. By taking these fluctuations into account, neural response (co)variability is significantly reduced, revealing the brain to be more reliable and predictable than previously thought.}, Author = {McGinley, Matthew J and Vinck, Martin and Reimer, Jacob and Batista-Brito, Renata and Zagha, Edward and Cadwell, Cathryn R and Tolias, Andreas S and Cardin, Jessica A and McCormick, David A}, Date-Added = {2016-07-01 15:31:16 +0000}, Date-Modified = {2016-07-01 15:31:16 +0000}, Doi = {10.1016/j.neuron.2015.09.012}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Action Potentials; Animals; Brain; Humans; Motor Activity; Nerve Net; Neurons; Time Factors; Wakefulness}, Month = {Sep}, Number = {6}, Pages = {1143-61}, Pmc = {PMC4718218}, pmid = {26402600}, Pst = {ppublish}, Title = {Waking State: Rapid Variations Modulate Neural and Behavioral Responses}, Volume = {87}, Year = {2015}, url = {papers/McGinley_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.09.012}} @article{McGinley:2015, Abstract = {The neural correlates of optimal states for signal detection task performance are largely unknown. One hypothesis holds that optimal states exhibit tonically depolarized cortical neurons with enhanced spiking activity, such as occur during movement. We recorded membrane potentials of auditory cortical neurons in mice trained on a challenging tone-in-noise detection task while assessing arousal with simultaneous pupillometry and hippocampal recordings. Arousal measures accurately predicted multiple modes of membrane potential activity, including rhythmic slow oscillations at low arousal, stable hyperpolarization at intermediate arousal, and depolarization during phasic or tonic periods of hyper-arousal. Walking always occurred during hyper-arousal. Optimal signal detection behavior and sound-evoked responses, at both sub-threshold and spiking levels, occurred at intermediate arousal when pre-decision membrane potentials were stably hyperpolarized. These results reveal a cortical physiological signature of the classically observed inverted-U relationship between task performance and arousal and that optimal detection exhibits enhanced sensory-evoked responses and reduced background synaptic activity.}, Author = {McGinley, Matthew J and David, Stephen V and McCormick, David A}, Date-Added = {2016-07-01 15:31:14 +0000}, Date-Modified = {2016-07-01 15:31:14 +0000}, Doi = {10.1016/j.neuron.2015.05.038}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Arousal; Auditory Cortex; Auditory Perception; Membrane Potentials; Mice; Neurons; Signal Detection, Psychological}, Month = {Jul}, Number = {1}, Pages = {179-92}, Pmc = {PMC4631312}, pmid = {26074005}, Pst = {ppublish}, Title = {Cortical Membrane Potential Signature of Optimal States for Sensory Signal Detection}, Volume = {87}, Year = {2015}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.05.038}} @article{Brockmann:2011, Abstract = {The coactivation of prefrontal and hippocampal networks in oscillatory rhythms is critical for precise information flow in mnemonic and executive tasks, yet the mechanisms governing its development are still unknown. Here, we demonstrate that already in neonatal rats, patterns of discontinuous oscillatory activity precisely entrain the firing of prefrontal neurons and have distinct spatial and temporal organization over cingulate and prelimbic cortices. Moreover, we show that hippocampal theta bursts drive the generation of neonatal prefrontal oscillations by phase-locking the neuronal firing via axonal pathways. Consequently, functional impairment of the hippocampus reduces the prefrontal activity. With ongoing maturation continuous theta-gamma oscillations emerge and mutually entrain the prejuvenile prefrontal-hippocampal networks. Thus, theta-modulated communication within developing prefrontal-hippocampal networks may be relevant for circuitry refinement and maturation of functional units underlying information storage at adulthood.}, Author = {Brockmann, Marco D and P{\"o}schel, Beatrice and Cichon, Nicole and Hanganu-Opatz, Ileana L}, Date-Added = {2016-07-01 15:29:23 +0000}, Date-Modified = {2016-07-01 15:29:23 +0000}, Doi = {10.1016/j.neuron.2011.05.041}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Action Potentials; Age Factors; Amino Acids; Analysis of Variance; Anesthetics, Local; Animals; Animals, Newborn; Biological Clocks; Electric Stimulation; Fourier Analysis; GABA Plasma Membrane Transport Proteins; Hippocampus; Lidocaine; N-Methylaspartate; Neural Pathways; Neurons; Parvalbumins; Prefrontal Cortex; Rats}, Month = {Jul}, Number = {2}, Pages = {332-47}, pmid = {21791291}, Pst = {ppublish}, Title = {Coupled oscillations mediate directed interactions between prefrontal cortex and hippocampus of the neonatal rat}, Volume = {71}, Year = {2011}, url = {papers/Brockmann_Neuron2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.05.041}} @article{Cichon:2014, Abstract = {Flexible communication within the brain, which relies on oscillatory activity, is not confined to adult neuronal networks. Experimental evidence has documented the presence of discontinuous patterns of oscillatory activity already during early development. Their highly variable spatial and time-frequency organization has been related to region specificity. However, it might be equally due to the absence of unitary criteria for classifying the early activity patterns, since they have been mainly characterized by visual inspection. Therefore, robust and unbiased methods for categorizing these discontinuous oscillations are needed for increasingly complex data sets from different labs. Here, we introduce an unsupervised detection and classification algorithm for the discontinuous activity patterns of rodents during early development. For this, in a first step time windows with discontinuous oscillations vs. epochs of network "silence" were identified. In a second step, the major features of detected events were identified and processed by principal component analysis for deciding on their contribution to the classification of different oscillatory patterns. Finally, these patterns were categorized using an unsupervised cluster algorithm. The results were validated on manually characterized neonatal spindle bursts (SB), which ubiquitously entrain neocortical areas of rats and mice, and prelimbic nested gamma spindle bursts (NG). Moreover, the algorithm led to satisfactory results for oscillatory events that, due to increased similarity of their features, were more difficult to classify, e.g., during the pre-juvenile developmental period. Based on a linear classification, the optimal number of features to consider increased with the difficulty of detection. This algorithm allows the comparison of neonatal and pre-juvenile oscillatory patterns in their spatial and temporal organization. It might represent a first step for the unbiased elucidation of activity patterns during development.}, Author = {Cichon, Nicole B and Denker, Michael and Gr{\"u}n, Sonja and Hanganu-Opatz, Ileana L}, Date-Added = {2016-07-01 15:27:21 +0000}, Date-Modified = {2016-07-01 15:27:21 +0000}, Doi = {10.3389/fncir.2014.00050}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {development; high-frequency oscillations; network oscillations; prefrontal cortex; principal component analysis; synchrony}, Mesh = {Action Potentials; Algorithms; Animals; Animals, Newborn; Neocortex; Nerve Net; Neurons; Rats; Rats, Wistar}, Pages = {50}, Pmc = {PMC4034041}, pmid = {24904296}, Pst = {epublish}, Title = {Unsupervised classification of neocortical activity patterns in neonatal and pre-juvenile rodents}, Volume = {8}, Year = {2014}, url = {papers/Cichon_FrontNeuralCircuits2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncir.2014.00050}} @article{Hoy:2015, Abstract = {The laminar structure and conserved cellular organization of mouse visual cortex provide a useful model to determine the mechanisms underlying the development of visual system function. However, the normal development of many receptive field properties has not yet been thoroughly quantified, particularly with respect to layer identity and in the absence of anesthesia. Here, we use multisite electrophysiological recording in the awake mouse across an extended period of development, starting at eye opening, to measure receptive field properties and behavioral-state modulation of responsiveness. We find selective responses for orientation, direction, and spatial frequency at eye opening, which are similar across cortical layers. After this initial similarity, we observe layer-specific maturation of orientation selectivity, direction selectivity, and linearity over the following week. Developmental increases in selectivity are most robust and similar between layers 2-4, whereas layers 5 and 6 undergo distinct refinement patterns. Finally, we studied layer-specific behavioral-state modulation of cortical activity and observed a striking reorganization in the effects of running on response gain. During week 1 after eye opening, running increases responsiveness in layers 4 and 5, whereas in adulthood, the effects of running are most pronounced in layer 2/3. Together, these data demonstrate that response selectivity is present in all layers of the primary visual cortex (V1) at eye opening in the awake mouse and identify the features of basic V1 function that are further shaped over this early developmental period in a layer-specific manner.}, Author = {Hoy, Jennifer L and Niell, Cristopher M}, Date-Added = {2016-07-01 15:14:41 +0000}, Date-Modified = {2016-07-01 15:14:41 +0000}, Doi = {10.1523/JNEUROSCI.3174-14.2015}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {V1; development; gain modulation; mouse; orientation selectivity; receptive field}, Mesh = {Animals; Brain Mapping; Eye Movements; Female; Male; Mice; Mice, Inbred C57BL; Neurons; Running; Spatial Navigation; Visual Cortex; Visual Fields; Wakefulness}, Month = {Feb}, Number = {8}, Pages = {3370-83}, Pmc = {PMC4339350}, pmid = {25716837}, Pst = {ppublish}, Title = {Layer-specific refinement of visual cortex function after eye opening in the awake mouse}, Volume = {35}, Year = {2015}, url = {papers/Hoy_JNeurosci2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3174-14.2015}} @article{Alivisatos:2013a, Abstract = {Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function.}, Author = {Alivisatos, A Paul and Andrews, Anne M and Boyden, Edward S and Chun, Miyoung and Church, George M and Deisseroth, Karl and Donoghue, John P and Fraser, Scott E and Lippincott-Schwartz, Jennifer and Looger, Loren L and Masmanidis, Sotiris and McEuen, Paul L and Nurmikko, Arto V and Park, Hongkun and Peterka, Darcy S and Reid, Clay and Roukes, Michael L and Scherer, Axel and Schnitzer, Mark and Sejnowski, Terrence J and Shepard, Kenneth L and Tsao, Doris and Turrigiano, Gina and Weiss, Paul S and Xu, Chris and Yuste, Rafael and Zhuang, Xiaowei}, Date-Added = {2016-07-01 12:27:41 +0000}, Date-Modified = {2016-07-01 12:27:41 +0000}, Doi = {10.1021/nn4012847}, Journal = {ACS Nano}, Journal-Full = {ACS nano}, Mesh = {Animals; Brain Mapping; Humans; Models, Neurological; Nanomedicine; Nanoparticles; Nanotechnology; Nervous System Physiological Phenomena}, Month = {Mar}, Number = {3}, Pages = {1850-66}, Pmc = {PMC3665747}, pmid = {23514423}, Pst = {ppublish}, Title = {Nanotools for neuroscience and brain activity mapping}, Volume = {7}, Year = {2013}, url = {papers/Alivisatos_ACSNano2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1021/nn4012847}} @article{Fenlon:2015a, Abstract = {BACKGROUND: Autism spectrum disorders (ASD) are a group of poorly understood behavioural disorders, which have increased in prevalence in the past two decades. Animal models offer the opportunity to understand the biological basis of these disorders. Studies comparing different mouse strains have identified the inbred BTBR T + tf/J (BTBR) strain as a mouse model of ASD based on its anti-social and repetitive behaviours. Adult BTBR mice have complete agenesis of the corpus callosum, reduced cortical thickness and changes in early neurogenesis. However, little is known about the development or ultimate organisation of cortical areas devoted to specific sensory and motor functions in these mice that may also contribute to their behavioural phenotype. RESULTS: In this study, we performed diffusion tensor imaging and tractography, together with histological analyses to investigate the emergence of functional areas in the cerebral cortex and their connections in BTBR mice and age-matched C57Bl/6 control mice. We found evidence that neither the anterior commissure nor the hippocampal commissure compensate for the loss of callosal connections, indicating that no interhemispheric neocortical connectivity is present in BTBR mice. We also found that both the primary visual and somatosensory cortical areas are shifted medially in BTBR mice compared to controls and that cortical thickness is differentially altered in BTBR mice between cortical areas and throughout development. CONCLUSIONS: We demonstrate that interhemispheric connectivity and cortical area formation are altered in an age- and region-specific manner in BTBR mice, which may contribute to the behavioural deficits previously observed in this strain. Some of these developmental patterns of change are also present in human ASD patients, and elucidating the aetiology driving cortical changes in BTBR mice may therefore help to increase our understanding of this disorder.}, Author = {Fenlon, Laura R and Liu, Sha and Gobius, Ilan and Kurniawan, Nyoman D and Murphy, Skyle and Moldrich, Randal X and Richards, Linda J}, Date-Added = {2016-07-01 12:08:40 +0000}, Date-Modified = {2016-07-01 12:10:18 +0000}, Doi = {10.1186/s13064-015-0033-y}, Journal = {Neural Dev}, Journal-Full = {Neural development}, Keywords = {development; corpus callosum; connectivity; neocortex; cerebral; activity-development;}, Mesh = {Agenesis of Corpus Callosum; Aging; Animals; Anterior Cerebellar Commissure; Autism Spectrum Disorder; Cerebral Cortex; Diffusion Tensor Imaging; Disease Models, Animal; Fornix, Brain; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Neurologic Mutants; Phenotype; Somatosensory Cortex; Visual Cortex}, Pages = {10}, Pmc = {PMC4412039}, pmid = {25879444}, Pst = {epublish}, Title = {Formation of functional areas in the cerebral cortex is disrupted in a mouse model of autism spectrum disorder}, Volume = {10}, Year = {2015}, url = {papers/Fenlon_NeuralDev2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/s13064-015-0033-y}} @article{Fenlon:2015, Abstract = {The corpus callosum connects the two cortical hemispheres of the mammalian brain and is susceptible to structural defects during development, which often result in significant neuropsychological dysfunction. To date, such individuals have been studied primarily with regards to the integrity of the callosal tract at the midline. However, the mechanisms regulating the contralateral targeting of the corpus callosum, after midline crossing has occurred, are less well understood. Recent evidence suggests that defects in contralateral targeting can occur in isolation from midline-tract malformations, and may have significant functional implications. We propose that contralateral targeting is a crucially important and relatively under-investigated event in callosal development, and that defects in this process may constitute an undiagnosed phenotype in several neurological disorders.}, Author = {Fenlon, Laura R and Richards, Linda J}, Date-Added = {2016-07-01 12:08:15 +0000}, Date-Modified = {2016-07-01 12:10:18 +0000}, Doi = {10.1016/j.tins.2015.02.007}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {autism; brain development; callosal dysgenesis; contralateral targeting; corpus callosum; schizophrenia; development; corpus callosum; connectivity; neocortex; cerebral; activity-development;}, Mesh = {Animals; Corpus Callosum; Functional Laterality; Humans; Mental Disorders; Neuroimaging}, Month = {May}, Number = {5}, Pages = {264-72}, pmid = {25841797}, Pst = {ppublish}, Title = {Contralateral targeting of the corpus callosum in normal and pathological brain function}, Volume = {38}, Year = {2015}, url = {papers/Fenlon_TrendsNeurosci2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2015.02.007}} @article{Kozberg:2016, Abstract = {UNLABELLED: In the adult brain, increases in neural activity lead to increases in local blood flow. However, many prior measurements of functional hemodynamics in the neonatal brain, including functional magnetic resonance imaging (fMRI) in human infants, have noted altered and even inverted hemodynamic responses to stimuli. Here, we demonstrate that localized neural activity in early postnatal mice does not evoke blood flow increases as in the adult brain, and elucidate the neural and metabolic correlates of these altered functional hemodynamics as a function of developmental age. Using wide-field GCaMP imaging, the development of neural responses to somatosensory stimulus is visualized over the entire bilaterally exposed cortex. Neural responses are observed to progress from tightly localized, unilateral maps to bilateral responses as interhemispheric connectivity becomes established. Simultaneous hemodynamic imaging confirms that spatiotemporally coupled functional hyperemia is not present during these early stages of postnatal brain development, and develops gradually as cortical connectivity is established. Exploring the consequences of this lack of functional hyperemia, measurements of oxidative metabolism via flavoprotein fluorescence suggest that neural activity depletes local oxygen to below baseline levels at early developmental stages. Analysis of hemoglobin oxygenation dynamics at the same age confirms oxygen depletion for both stimulus-evoked and resting-state neural activity. This state of unmet metabolic demand during neural network development poses new questions about the mechanisms of neurovascular development and its role in both normal and abnormal brain development. These results also provide important insights for the interpretation of fMRI studies of the developing brain. SIGNIFICANCE STATEMENT: This work demonstrates that the postnatal development of neuronal connectivity is accompanied by development of the mechanisms that regulate local blood flow in response to neural activity. Novel in vivo imaging reveals that, in the developing mouse brain, strong and localized GCaMP neural responses to stimulus fail to evoke local blood flow increases, leading to a state in which oxygen levels become locally depleted. These results demonstrate that the development of cortical connectivity occurs in an environment of altered energy availability that itself may play a role in shaping normal brain development. These findings have important implications for understanding the pathophysiology of abnormal developmental trajectories, and for the interpretation of functional magnetic resonance imaging data acquired in the developing brain.}, Author = {Kozberg, Mariel G and Ma, Ying and Shaik, Mohammed A and Kim, Sharon H and Hillman, Elizabeth M C}, Date-Added = {2016-07-01 12:05:59 +0000}, Date-Modified = {2016-07-01 12:05:59 +0000}, Doi = {10.1523/JNEUROSCI.2363-15.2016}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {GCaMP imaging; fMRI; flavoprotein fluorescence; functional hyperemia; neurovascular coupling; oxygen consumption; postnatal neural development}, Month = {Jun}, Number = {25}, Pages = {6704-17}, pmid = {27335402}, Pst = {ppublish}, Title = {Rapid Postnatal Expansion of Neural Networks Occurs in an Environment of Altered Neurovascular and Neurometabolic Coupling}, Volume = {36}, Year = {2016}, url = {papers/Kozberg_JNeurosci2016.pdf}} @article{Wise:1978, Author = {Wise, S P and Jones, E G}, Date-Added = {2016-05-13 20:02:41 +0000}, Date-Modified = {2016-05-13 20:02:41 +0000}, Doi = {10.1002/cne.901780202}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Age Factors; Animals; Corpus Striatum; Functional Laterality; Neural Pathways; Rats; Somatosensory Cortex; Thalamic Nuclei; Thalamus}, Month = {Mar}, Number = {2}, Pages = {187-208}, pmid = {627623}, Pst = {ppublish}, Title = {Developmental studies of thalamocortical and commissural connections in the rat somatic sensory cortex}, Volume = {178}, Year = {1978}, url = {papers/Wise_JCompNeurol1978.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901780202}} @article{Wise:1977, Abstract = {The retrograde, horseradish peroxidase technique has been used to demonstrate the cells of origin of corticofugal fiber systems arising in the rat somatic sensory cortex and projecting to the striatum, diencephalon, brainstem, and spinal cord. Correlative experiments conducted with the anterograde, autoradiographic method have been used to confirm the terminal distribution of many of these fiber systems. Corticofugal pathways directed to subcortical structures arise in the first and second somatic sensory areas exclusively from pyramidal cells of the infragranular layers, V and VI. Fibers which descend to the midbrain, pons, medulla and spinal cord arise exclusively from the largest pyramidal cells, the somata of which are found in the deep part of layer V (layer VB). There is some evidence for a sublaminar organization of the different classes of efferent cells within this layer. Fibers projecting to the diencephalon arise from somata situated throughout layer VI and to a lesser extent in layer V. Corticostriatal fibers arise only from cells with somata in layer V, but the somata are more superficially situated than those of the other classes of corticofugal neurons. The laminar distribution of the somata of corticofugal neurons differs considerably from that of commissural and ipsilateral corticocortical neurons.}, Author = {Wise, S P and Jones, E G}, Date-Added = {2016-05-13 20:02:38 +0000}, Date-Modified = {2016-05-13 20:02:38 +0000}, Doi = {10.1002/cne.901750202}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Autoradiography; Brain Mapping; Cats; Corpus Striatum; Diencephalon; Haplorhini; Medulla Oblongata; Mesencephalon; Neural Pathways; Neurons, Efferent; Pons; Pyramidal Tracts; Rats; Somatosensory Cortex; Tectum Mesencephali; Thalamus}, Month = {Sep}, Number = {2}, Pages = {129-57}, pmid = {408380}, Pst = {ppublish}, Title = {Cells of origin and terminal distribution of descending projections of the rat somatic sensory cortex}, Volume = {175}, Year = {1977}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901750202}} @article{Wise:1976, Abstract = {Anterograde and retrograde tracing experiments have been used to demonstrate the origin and terminal distribution of commissural fibers in the first somatosensory cortex (SI) of the rat. The commissural fibers originate from pyramidal cells of all layers, but predominantly from layers III and V. The fibers terminate in a series of approximately vertical bands. In each of these there are concentrations of terminals extending from the inner portion of the molecular layer to the deep portion of layer III as well as in the superficial part of layer V, and in layer VI. Discrete vertical bands of cortex are reciprocally connected across the midline to give both the origin and terminal regions of the projection a patchy or "columnar" appearance. The commissural fibers arise from and terminate in areas of the cortex that lie between and alongside the aggregations of granule cells that distinguish SI of the rat. No commissural fibers terminate within the aggregations of layer IV cells themselves but the more superficial terminal ramifications may come to overlie these aggregations. A heterotopic projection to the contralateral second somatosensory cortex has been observed and is similar in form to the homotopic projection to SI. Many commissural fibers have crossed the midline in the corpus callosum by the day of birth but lie in the underlying white matter and do not enter the cortical plate until at least the third postnatal day. During the first postnatal week these fibers grow somewhat diffusely into the maturing cortex and their topographic and laminar pattern of distribution attains its adult characteristics by the end of the first week. Commissural axons, thus, arise from immature cells but the maturation of cell form seems to precede the ingrowth of these axons and the acquisition of commissural synapses.}, Author = {Wise, S P and Jones, E G}, Date-Added = {2016-05-13 20:02:37 +0000}, Date-Modified = {2016-05-13 20:02:37 +0000}, Doi = {10.1002/cne.901680302}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Corpus Callosum; Neural Pathways; Rats; Somatosensory Cortex}, Month = {Aug}, Number = {3}, Pages = {313-43}, pmid = {950383}, Pst = {ppublish}, Title = {The organization and postnatal development of the commissural projection of the rat somatic sensory cortex}, Volume = {168}, Year = {1976}, url = {papers/Wise_JCompNeurol1976.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901680302}} @article{Mohajerani:2013, Abstract = {Using millisecond-timescale voltage-sensitive dye imaging in lightly anesthetized or awake adult mice, we show that a palette of sensory-evoked and hemisphere-wide activity motifs are represented in spontaneous activity. These motifs can reflect multiple modes of sensory processing, including vision, audition and touch. We found similar cortical networks with direct cortical activation using channelrhodopsin-2. Regional analysis of activity spread indicated modality-specific sources, such as primary sensory areas, a common posterior-medial cortical sink where sensory activity was extinguished within the parietal association area and a secondary anterior medial sink within the cingulate and secondary motor cortices for visual stimuli. Correlation analysis between functional circuits and intracortical axonal projections indicated a common framework corresponding to long-range monosynaptic connections between cortical regions. Maps of intracortical monosynaptic structural connections predicted hemisphere-wide patterns of spontaneous and sensory-evoked depolarization. We suggest that an intracortical monosynaptic connectome shapes the ebb and flow of spontaneous cortical activity.}, Author = {Mohajerani, Majid H and Chan, Allen W and Mohsenvand, Mostafa and LeDue, Jeffrey and Liu, Rui and McVea, David A and Boyd, Jamie D and Wang, Yu Tian and Reimers, Mark and Murphy, Timothy H}, Date-Added = {2016-04-04 23:31:45 +0000}, Date-Modified = {2016-04-04 23:31:45 +0000}, Doi = {10.1038/nn.3499}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Acoustic Stimulation; Animals; Auditory Cortex; Axons; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Photic Stimulation; Visual Cortex}, Month = {Oct}, Number = {10}, Pages = {1426-35}, Pmc = {PMC3928052}, pmid = {23974708}, Pst = {ppublish}, Title = {Spontaneous cortical activity alternates between motifs defined by regional axonal projections}, Volume = {16}, Year = {2013}, url = {papers/Mohajerani_NatNeurosci2013.pdf}, Bdsk-File-2 = {papers/Mohajerani_NatNeurosci2013a.pdf}} @article{Feinberg:2015, Abstract = {More than twenty types of retinal ganglion cells conduct visual information from the eye to the rest of the brain. Each retinal ganglion cell type tessellates the retina in a regular mosaic, so that every point in visual space is processed for visual primitives such as contrast and motion. This information flows to two principal brain centres: the visual cortex and the superior colliculus. The superior colliculus plays an evolutionarily conserved role in visual behaviours, but its functional architecture is poorly understood. Here we report on population recordings of visual responses from neurons in the mouse superior colliculus. Many neurons respond preferentially to lines of a certain orientation or movement axis. We show that cells with similar orientation preferences form large patches that span the vertical thickness of the retinorecipient layers. This organization is strikingly different from the randomly interspersed orientation preferences in the mouse's visual cortex; instead, it resembles the orientation columns observed in the visual cortices of large mammals. Notably, adjacent superior colliculus orientation columns have only limited receptive field overlap. This is in contrast to the organization of visual cortex, where each point in the visual field activates neurons with all preferred orientations. Instead, the superior colliculus favours specific contour orientations within ∼30$\,^{\circ}$ regions of the visual field, a finding with implications for behavioural responses mediated by this brain centre.}, Author = {Feinberg, Evan H and Meister, Markus}, Date-Added = {2016-03-21 23:37:59 +0000}, Date-Modified = {2016-03-21 23:37:59 +0000}, Doi = {10.1038/nature14103}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Brain Mapping; Calcium; Female; Male; Mice; Mice, Inbred C57BL; Motion; Neurons; Orientation; Photic Stimulation; Superior Colliculi; Visual Cortex; Visual Fields; Wakefulness}, Month = {Mar}, Number = {7542}, Pages = {229-32}, pmid = {25517100}, Pst = {ppublish}, Title = {Orientation columns in the mouse superior colliculus}, Volume = {519}, Year = {2015}, url = {papers/Feinberg_Nature2015.pdf}, Bdsk-File-2 = {papers/Feinberg_Nature2015b.pdf}, Bdsk-File-3 = {papers/Feinberg_Nature2015.jpg}, Bdsk-File-4 = {papers/Feinberg_Nature2015a.jpg}, Bdsk-File-5 = {papers/Feinberg_Nature2015b.jpg}, Bdsk-File-6 = {papers/Feinberg_Nature2015c.jpg}, Bdsk-File-7 = {papers/Feinberg_Nature2015d.jpg}, Bdsk-File-8 = {papers/Feinberg_Nature2015e.jpg}, Bdsk-File-9 = {papers/Feinberg_Nature2015f.jpg}, File0 = {papers/Feinberg_Nature2015g.jpg}} @article{Guadiana:2013, Abstract = {The formation of primary cilia is a highly choreographed process that can be disrupted in developing neurons by overexpressing neuromodulatory G-protein-coupled receptors GPCRs or by blocking intraflagellar transport. Here, we examined the effects of overexpressing the ciliary GPCRs, 5HT6 and SSTR3, on cilia structure and the differentiation of neocortical neurons. Neuronal overexpression of 5HT6 and SSTR3 was achieved by electroporating mouse embryo cortex in utero with vectors encoding these receptors. We found that overexpression of ciliary GPCRs in cortical neurons, especially 5HT6, induced the formation of long (>30 μm) and often forked cilia. These changes were associated with increased levels of intraflagellar transport proteins and accelerated ciliogenesis in neonatal neocortex, the induction of which required Kif3a, an anterograde motor critical for cilia protein trafficking and growth. GPCR overexpression also altered the complement of signaling molecules within the cilia. We found that SSTR3 and type III adenylyl cyclase (ACIII), proteins normally enriched in neuronal cilia, were rarely detected in 5HT6-elongated cilia. Intriguingly, the changes in cilia structure were accompanied by changes in neuronal morphology. Specifically, disruption of normal ciliogenesis in developing neocortical neurons, either by overexpressing cilia GPCRs or a dominant-negative form of Kif3a, significantly impaired dendrite outgrowth. Remarkably, coexpression of ACIII with 5HT6 restored ACIII to cilia, normalized cilia structure, and restored dendrite outgrowth, effects that were not observed in neurons coexpressing ACIII and dominant-negative form of Kif3a. Collectively, our data suggest the formation of neuronal dendrites in developing neocortex requires structurally normal cilia enriched with ACIII.}, Author = {Guadiana, Sarah M and Semple-Rowland, Susan and Daroszewski, Daniel and Madorsky, Irina and Breunig, Joshua J and Mykytyn, Kirk and Sarkisian, Matthew R}, Date-Added = {2016-03-18 17:31:34 +0000}, Date-Modified = {2016-03-18 17:31:34 +0000}, Doi = {10.1523/JNEUROSCI.2906-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Adenylyl Cyclases; Animals; Cells, Cultured; Cilia; Dendrites; Female; Kinesin; Male; Mice; NIH 3T3 Cells; Neocortex; Neurogenesis; Neurons; Pregnancy; Receptors, Serotonin}, Month = {Feb}, Number = {6}, Pages = {2626-38}, pmid = {23392690}, Pst = {ppublish}, Title = {Arborization of dendrites by developing neocortical neurons is dependent on primary cilia and type 3 adenylyl cyclase}, Volume = {33}, Year = {2013}, url = {papers/Guadiana_JNeurosci2013.pdf}} @article{Breunig:2015, Abstract = {As the list of putative driver mutations in glioma grows, we are just beginning to elucidate the effects of dysregulated developmental signaling pathways on the transformation of neural cells. We have employed a postnatal, mosaic, autochthonous glioma model that captures the first hours and days of gliomagenesis in more resolution than conventional genetically engineered mouse models of cancer. We provide evidence that disruption of the Nf1-Ras pathway in the ventricular zone at multiple signaling nodes uniformly results in rapid neural stem cell depletion, progenitor hyperproliferation, and gliogenic lineage restriction. Abolishing Ets subfamily activity, which is upregulated downstream of Ras, rescues these phenotypes and blocks glioma initiation. Thus, the Nf1-Ras-Ets axis might be one of the select molecular pathways that are perturbed for initiation and maintenance in glioma.}, Author = {Breunig, Joshua J and Levy, Rachelle and Antonuk, C Danielle and Molina, Jessica and Dutra-Clarke, Marina and Park, Hannah and Akhtar, Aslam Abbasi and Kim, Gi Bum and Hu, Xin and Bannykh, Serguei I and Verhaak, Roel G W and Danielpour, Moise}, Date-Added = {2016-03-18 17:31:15 +0000}, Date-Modified = {2016-03-18 17:31:15 +0000}, Doi = {10.1016/j.celrep.2015.06.012}, Journal = {Cell Rep}, Journal-Full = {Cell reports}, Month = {Jul}, Number = {2}, Pages = {258-71}, pmid = {26146073}, Pst = {ppublish}, Title = {Ets Factors Regulate Neural Stem Cell Depletion and Gliogenesis in Ras Pathway Glioma}, Volume = {12}, Year = {2015}, url = {papers/Breunig_CellRep2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.celrep.2015.06.012}} @article{Zeisel:2015, Abstract = {The mammalian cerebral cortex supports cognitive functions such as sensorimotor integration, memory, and social behaviors. Normal brain function relies on a diverse set of differentiated cell types, including neurons, glia, and vasculature. Here, we have used large-scale single-cell RNA sequencing (RNA-seq) to classify cells in the mouse somatosensory cortex and hippocampal CA1 region. We found 47 molecularly distinct subclasses, comprising all known major cell types in the cortex. We identified numerous marker genes, which allowed alignment with known cell types, morphology, and location. We found a layer I interneuron expressing Pax6 and a distinct postmitotic oligodendrocyte subclass marked by Itpr2. Across the diversity of cortical cell types, transcription factors formed a complex, layered regulatory code, suggesting a mechanism for the maintenance of adult cell type identity.}, Author = {Zeisel, Amit and Mu{\~n}oz-Manchado, Ana B and Codeluppi, Simone and L{\"o}nnerberg, Peter and La Manno, Gioele and Jur{\'e}us, Anna and Marques, Sueli and Munguba, Hermany and He, Liqun and Betsholtz, Christer and Rolny, Charlotte and Castelo-Branco, Gon{\c c}alo and Hjerling-Leffler, Jens and Linnarsson, Sten}, Date-Added = {2016-03-17 21:14:22 +0000}, Date-Modified = {2016-03-17 21:15:48 +0000}, Doi = {10.1126/science.aaa1934}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {mouse; mice; technique; Methods; RNAseq}, Mesh = {Animals; CA1 Region, Hippocampal; Eye Proteins; Gene Expression; Genetic Markers; Homeodomain Proteins; Inositol 1,4,5-Trisphosphate Receptors; Interneurons; Mice; Oligodendroglia; Paired Box Transcription Factors; Phylogeny; Repressor Proteins; Sequence Analysis, RNA; Single-Cell Analysis; Somatosensory Cortex; Transcription Factors; Transcriptome}, Month = {Mar}, Number = {6226}, Pages = {1138-42}, pmid = {25700174}, Pst = {ppublish}, Title = {Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq}, Volume = {347}, Year = {2015}, url = {papers/Zeisel_Science2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.aaa1934}} @article{Perez-Cadahia:2011, Abstract = {Immediate-early genes have important roles in processes such as brain development, learning, and responses to drug abuse. Further, immediate-early genes play an essential role in cellular responses that contribute to long-term neuronal plasticity. Neuronal plasticity is a characteristic of the nervous system that is not limited to the first stages of brain development but persists in adulthood and seems to be an inherent feature of everyday brain function. The plasticity refers to the neuron's capability of showing short- or long-lasting phenotypic changes in response to different stimuli and cellular scenarios. In this review, we focus on the immediate-early genes encoding transcription factors (AP-1 and Egr) that are relevant for neuronal responses. Our current understanding of the mechanisms involved in the induction of the immediate-early genes is presented.}, Author = {P{\'e}rez-Cadah{\'\i}a, Beatriz and Drobic, Bojan and Davie, James R}, Date-Added = {2016-03-17 21:12:26 +0000}, Date-Modified = {2016-03-17 21:13:09 +0000}, Doi = {10.1139/O10-138}, Journal = {Biochem Cell Biol}, Journal-Full = {Biochemistry and cell biology = Biochimie et biologie cellulaire}, Keywords = {Immediate-Early; gene; IEG; Transcription Factors; activity-development; activity manipulation}, Mesh = {Animals; Brain; Early Growth Response Protein 1; Genes, Immediate-Early; Humans; Nervous System Physiological Phenomena; Neuronal Plasticity; Neurons; Signal Transduction; Transcription Factor AP-1; Transcription Factors; Transcriptional Activation}, Month = {Feb}, Number = {1}, Pages = {61-73}, pmid = {21326363}, Pst = {ppublish}, Title = {Activation and function of immediate-early genes in the nervous system}, Volume = {89}, Year = {2011}, url = {papers/Pérez-Cadahía_BiochemCellBiol2011.pdf}} @article{Meyza:2015, Abstract = {Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized, in part, by an inability to adequately respond to social cues. Patients diagnosed with ASD are often devoid of empathy and impaired in understanding other people's emotional perspective. The neuronal correlates of this impairment are not fully understood. Replicating such a behavioral phenotype in a mouse model of autism would allow us insight into the neuronal background of the problem. Here we tested BTBR T(+)Itpr3(tf)/J (BTBR) and c57BL/6J (B6) mice in two behavioral paradigms: the Transfer of Emotional Information test and the Social Proximity test. In both tests BTBR mice displayed asocial behavior. We analyzed c-Fos protein expression in several brain regions after each of these tests, and found that, unlike B6 mice, BTBR mice react to a stressed cagemate exposure in the Transfer of Emotional Information test with no increase of c-Fos expression in either the prefrontal cortex or the amygdala. However, after Social Proximity exposure we observed a strong increase in c-Fos expression in the CA3 field of the hippocampus and two hypothalamic regions of BTBR brains. This response was accompanied by a strong activation of periaqueductal regions related to defensiveness, which suggests that BTBR mice find unavoidable social interaction highly aversive.}, Author = {Meyza, Ksenia and Nikolaev, Tomasz and Kondrakiewicz, Kacper and Blanchard, D Caroline and Blanchard, Robert J and Knapska, Ewelina}, Date-Added = {2016-03-17 21:12:03 +0000}, Date-Modified = {2016-03-17 21:12:03 +0000}, Doi = {10.3389/fnbeh.2015.00199}, Journal = {Front Behav Neurosci}, Journal-Full = {Frontiers in behavioral neuroscience}, Keywords = {BTBR; autism; c-Fos; empathy; mouse model}, Pages = {199}, Pmc = {PMC4526814}, pmid = {26300749}, Pst = {epublish}, Title = {Neuronal correlates of asocial behavior in a BTBR T (+) Itpr3(tf)/J mouse model of autism}, Volume = {9}, Year = {2015}, url = {papers/Meyza_FrontBehavNeurosci2015.pdf}} @article{Darmanis:2015, Abstract = {The human brain is a tissue of vast complexity in terms of the cell types it comprises. Conventional approaches to classifying cell types in the human brain at single cell resolution have been limited to exploring relatively few markers and therefore have provided a limited molecular characterization of any given cell type. We used single cell RNA sequencing on 466 cells to capture the cellular complexity of the adult and fetal human brain at a whole transcriptome level. Healthy adult temporal lobe tissue was obtained during surgical procedures where otherwise normal tissue was removed to gain access to deeper hippocampal pathology in patients with medical refractory seizures. We were able to classify individual cells into all of the major neuronal, glial, and vascular cell types in the brain. We were able to divide neurons into individual communities and show that these communities preserve the categorization of interneuron subtypes that is typically observed with the use of classic interneuron markers. We then used single cell RNA sequencing on fetal human cortical neurons to identify genes that are differentially expressed between fetal and adult neurons and those genes that display an expression gradient that reflects the transition between replicating and quiescent fetal neuronal populations. Finally, we observed the expression of major histocompatibility complex type I genes in a subset of adult neurons, but not fetal neurons. The work presented here demonstrates the applicability of single cell RNA sequencing on the study of the adult human brain and constitutes a first step toward a comprehensive cellular atlas of the human brain.}, Author = {Darmanis, Spyros and Sloan, Steven A and Zhang, Ye and Enge, Martin and Caneda, Christine and Shuer, Lawrence M and Hayden Gephart, Melanie G and Barres, Ben A and Quake, Stephen R}, Date-Added = {2016-03-17 21:11:49 +0000}, Date-Modified = {2016-03-17 21:11:49 +0000}, Doi = {10.1073/pnas.1507125112}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {RNAseq; human brain; interneurons; neurons; single cells}, Mesh = {Adult; Brain; HLA Antigens; Humans; Neurons; Sequence Analysis, RNA; Single-Cell Analysis; Transcriptome}, Month = {Jun}, Number = {23}, Pages = {7285-90}, Pmc = {PMC4466750}, pmid = {26060301}, Pst = {ppublish}, Title = {A survey of human brain transcriptome diversity at the single cell level}, Volume = {112}, Year = {2015}, url = {papers/Darmanis_ProcNatlAcadSciUSA2015.pdf}} @article{Zhang:2014a, Abstract = {The major cell classes of the brain differ in their developmental processes, metabolism, signaling, and function. To better understand the functions and interactions of the cell types that comprise these classes, we acutely purified representative populations of neurons, astrocytes, oligodendrocyte precursor cells, newly formed oligodendrocytes, myelinating oligodendrocytes, microglia, endothelial cells, and pericytes from mouse cerebral cortex. We generated a transcriptome database for these eight cell types by RNA sequencing and used a sensitive algorithm to detect alternative splicing events in each cell type. Bioinformatic analyses identified thousands of new cell type-enriched genes and splicing isoforms that will provide novel markers for cell identification, tools for genetic manipulation, and insights into the biology of the brain. For example, our data provide clues as to how neurons and astrocytes differ in their ability to dynamically regulate glycolytic flux and lactate generation attributable to unique splicing of PKM2, the gene encoding the glycolytic enzyme pyruvate kinase. This dataset will provide a powerful new resource for understanding the development and function of the brain. To ensure the widespread distribution of these datasets, we have created a user-friendly website (http://web.stanford.edu/group/barres_lab/brain_rnaseq.html) that provides a platform for analyzing and comparing transciption and alternative splicing profiles for various cell classes in the brain.}, Author = {Zhang, Ye and Chen, Kenian and Sloan, Steven A and Bennett, Mariko L and Scholze, Anja R and O'Keeffe, Sean and Phatnani, Hemali P and Guarnieri, Paolo and Caneda, Christine and Ruderisch, Nadine and Deng, Shuyun and Liddelow, Shane A and Zhang, Chaolin and Daneman, Richard and Maniatis, Tom and Barres, Ben A and Wu, Jian Qian}, Date-Added = {2016-03-17 21:06:04 +0000}, Date-Modified = {2016-03-17 21:06:54 +0000}, Doi = {10.1523/JNEUROSCI.1860-14.2014}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {alternative splicing; astrocytes; microglia; oligodendrocytes; transcriptome; vascular cells; Methods; RNAseq; technique}, Mesh = {Alternative Splicing; Animals; Cerebral Cortex; Databases, Nucleic Acid; Endothelium, Vascular; Mice; Neuroglia; Neurons; Sequence Analysis, RNA; Transcriptome}, Month = {Sep}, Number = {36}, Pages = {11929-47}, Pmc = {PMC4152602}, pmid = {25186741}, Pst = {ppublish}, Title = {An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex}, Volume = {34}, Year = {2014}, url = {papers/Zhang_JNeurosci2014.pdf}} @article{Schmolesky:1998, Abstract = {The onset latencies of single-unit responses evoked by flashing visual stimuli were measured in the parvocellular (P) and magnocellular (M) layers of the dorsal lateral geniculate nucleus (LGNd) and in cortical visual areas V1, V2, V3, V4, middle temporal area (MT), medial superior temporal area (MST), and in the frontal eye field (FEF) in individual anesthetized monkeys. Identical procedures were carried out to assess latencies in each area, often in the same monkey, thereby permitting direct comparisons of timing across areas. This study presents the visual flash-evoked latencies for cells in areas where such data are common (V1 and V2), and are therefore a good standard, and also in areas where such data are sparse (LGNd M and P layers, MT, V4) or entirely lacking (V3, MST, and FEF in anesthetized preparation). Visual-evoked onset latencies were, on average, 17 ms shorter in the LGNd M layers than in the LGNd P layers. Visual responses occurred in V1 before any other cortical area. The next wave of activation occurred concurrently in areas V3, MT, MST, and FEF. Visual response latencies in areas V2 and V4 were progressively later and more broadly distributed. These differences in the time course of activation across the dorsal and ventral streams provide important temporal constraints on theories of visual processing.}, Author = {Schmolesky, M T and Wang, Y and Hanes, D P and Thompson, K G and Leutgeb, S and Schall, J D and Leventhal, A G}, Date-Added = {2016-03-14 19:27:14 +0000}, Date-Modified = {2016-03-14 19:29:40 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {neurophysiology; Classical/physiology; monkey; visual system; visual cortex; retina; LGN; Thalamic Nuclei; topographic map; Stimulation; conduction velocity; retina; response latency}, Mesh = {Animals; Evoked Potentials, Visual; Macaca; Neurons; Photic Stimulation; Signal Transduction; Time Factors; Vision, Ocular; Visual Cortex}, Month = {Jun}, Number = {6}, Pages = {3272-8}, pmid = {9636126}, Pst = {ppublish}, Title = {Signal timing across the macaque visual system}, Volume = {79}, Year = {1998}, url = {papers/Schmolesky_JNeurophysiol1998.pdf}} @article{Rash:2016, Abstract = {Cortical columns are basic cellular and functional units of the cerebral cortex that are malformed in many brain disorders, but how they initially develop is not well understood. Using an optogenetic sensor in the mouse embryonic forebrain, we demonstrate that Ca(2+) fluxes propagate bidirectionally within the elongated fibers of radial glial cells (RGCs), providing a novel communication mechanism linking the proliferative and postmitotic zones before the onset of synaptogenesis. Our results indicate that Ca(2+) activity along RGC fibers provides feedback information along the radial migratory pathway, influencing neurogenesis and migration during early column development. Furthermore, we find that this columnar Ca(2+) propagation is induced by Notch and fibroblast growth factor activities classically implicated in cortical expansion and patterning. Thus, cortical morphogens and growth factors may influence cortical column assembly in part by regulating long-distance Ca(2+) communication along the radial axis of cortical development.}, Author = {Rash, Brian G and Ackman, James B and Rakic, Pasko}, Date-Added = {2016-03-14 19:25:35 +0000}, Date-Modified = {2016-03-14 19:25:35 +0000}, Doi = {10.1126/sciadv.1501733}, Journal = {Sci Adv}, Journal-Full = {Science advances}, Keywords = {Calcium; GCaMP; migration; neuron; radial glial cells}, Month = {Feb}, Number = {2}, Pages = {e1501733}, Pmc = {PMC4771444}, pmid = {26933693}, Pst = {epublish}, Title = {Bidirectional radial Ca(2+) activity regulates neurogenesis and migration during early cortical column formation}, Volume = {2}, Year = {2016}, url = {papers/Rash_SciAdv2016.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/sciadv.1501733}} @article{Chen:2011a, Abstract = {The taste system is one of our fundamental senses, responsible for detecting and responding to sweet, bitter, umami, salty, and sour stimuli. In the tongue, the five basic tastes are mediated by separate classes of taste receptor cells each finely tuned to a single taste quality. We explored the logic of taste coding in the brain by examining how sweet, bitter, umami, and salty qualities are represented in the primary taste cortex of mice. We used in vivo two-photon calcium imaging to demonstrate topographic segregation in the functional architecture of the gustatory cortex. Each taste quality is represented in its own separate cortical field, revealing the existence of a gustotopic map in the brain. These results expose the basic logic for the central representation of taste.}, Author = {Chen, Xiaoke and Gabitto, Mariano and Peng, Yueqing and Ryba, Nicholas J P and Zuker, Charles S}, Date-Added = {2016-03-14 19:24:33 +0000}, Date-Modified = {2016-03-14 19:24:48 +0000}, Doi = {10.1126/science.1204076}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Animals; Appetitive Behavior; Avoidance Learning; Brain Mapping; Cerebral Cortex; Discrimination (Psychology); Male; Mice; Mice, Inbred C57BL; Optogenetics; Stereotaxic Techniques; Taste; Taste Perception; Wakefulness}, Mesh = {Afferent Pathways; Animals; Brain Mapping; Cerebral Cortex; Cycloheximide; Mice; Mice, Inbred C57BL; Mice, Knockout; Molecular Imaging; Neurons; Sodium Chloride; Sodium Glutamate; Sweetening Agents; Taste; Taste Buds}, Month = {Sep}, Number = {6047}, Pages = {1262-6}, Pmc = {PMC3523322}, pmid = {21885776}, Pst = {ppublish}, Title = {A gustotopic map of taste qualities in the mammalian brain}, Volume = {333}, Year = {2011}, url = {papers/Chen_Science2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1204076}} @article{Peng:2015, Abstract = {Taste is responsible for evaluating the nutritious content of food, guiding essential appetitive behaviours, preventing the ingestion of toxic substances, and helping to ensure the maintenance of a healthy diet. Sweet and bitter are two of the most salient sensory percepts for humans and other animals; sweet taste allows the identification of energy-rich nutrients whereas bitter warns against the intake of potentially noxious chemicals. In mammals, information from taste receptor cells in the tongue is transmitted through multiple neural stations to the primary gustatory cortex in the brain. Recent imaging studies have shown that sweet and bitter are represented in the primary gustatory cortex by neurons organized in a spatial map, with each taste quality encoded by distinct cortical fields. Here we demonstrate that by manipulating the brain fields representing sweet and bitter taste we directly control an animal's internal representation, sensory perception, and behavioural actions. These results substantiate the segregation of taste qualities in the cortex, expose the innate nature of appetitive and aversive taste responses, and illustrate the ability of gustatory cortex to recapitulate complex behaviours in the absence of sensory input.}, Author = {Peng, Yueqing and Gillis-Smith, Sarah and Jin, Hao and Tr{\"a}nkner, Dimitri and Ryba, Nicholas J P and Zuker, Charles S}, Date-Added = {2016-03-14 19:23:44 +0000}, Date-Modified = {2016-03-14 19:23:59 +0000}, Doi = {10.1038/nature15763}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Animals; Appetitive Behavior; Avoidance Learning; Brain Mapping; Cerebral Cortex; Discrimination (Psychology); Male; Mice; Mice, Inbred C57BL; Optogenetics; Stereotaxic Techniques; Taste; Taste Perception; Wakefulness}, Mesh = {Animals; Appetitive Behavior; Avoidance Learning; Brain Mapping; Cerebral Cortex; Discrimination (Psychology); Male; Mice; Mice, Inbred C57BL; Optogenetics; Stereotaxic Techniques; Taste; Taste Perception; Wakefulness}, Month = {Nov}, Number = {7579}, Pages = {512-5}, Pmc = {PMC4712381}, pmid = {26580015}, Pst = {ppublish}, Title = {Sweet and bitter taste in the brain of awake behaving animals}, Volume = {527}, Year = {2015}, url = {papers/Peng_Nature2015.pdf}} @article{Zhang:2003c, Abstract = {Mammals can taste a wide repertoire of chemosensory stimuli. Two unrelated families of receptors (T1Rs and T2Rs) mediate responses to sweet, amino acids, and bitter compounds. Here, we demonstrate that knockouts of TRPM5, a taste TRP ion channel, or PLCbeta2, a phospholipase C selectively expressed in taste tissue, abolish sweet, amino acid, and bitter taste reception, but do not impact sour or salty tastes. Therefore, despite relying on different receptors, sweet, amino acid, and bitter transduction converge on common signaling molecules. Using PLCbeta2 taste-blind animals, we then examined a fundamental question in taste perception: how taste modalities are encoded at the cellular level. Mice engineered to rescue PLCbeta2 function exclusively in bitter-receptor expressing cells respond normally to bitter tastants but do not taste sweet or amino acid stimuli. Thus, bitter is encoded independently of sweet and amino acids, and taste receptor cells are not broadly tuned across these modalities.}, Author = {Zhang, Yifeng and Hoon, Mark A and Chandrashekar, Jayaram and Mueller, Ken L and Cook, Boaz and Wu, Dianqing and Zuker, Charles S and Ryba, Nicholas J P}, Date-Added = {2016-03-14 19:22:34 +0000}, Date-Modified = {2016-03-14 19:23:08 +0000}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {Action Potentials; Animals; Cell Membrane; Cells, Cultured; Citric Acid; Female; GTP-Binding Proteins; Glutamic Acid; Isoenzymes; Male; Membrane Proteins; Mice; Mice, Knockout; Neurons, Afferent; Phospholipase C beta; Quinine; Receptors, Cell Surface; Sensory Receptor Cells; Signal Transduction; Sucrose; TRPM Cation Channels; Taste; Taste Buds; Type C Phospholipases}, Mesh = {Action Potentials; Animals; Cell Membrane; Cells, Cultured; Citric Acid; Female; GTP-Binding Proteins; Glutamic Acid; Isoenzymes; Male; Membrane Proteins; Mice; Mice, Knockout; Neurons, Afferent; Phospholipase C beta; Quinine; Receptors, Cell Surface; Sensory Receptor Cells; Signal Transduction; Sucrose; TRPM Cation Channels; Taste; Taste Buds; Type C Phospholipases}, Month = {Feb}, Number = {3}, Pages = {293-301}, pmid = {12581520}, Pst = {ppublish}, Title = {Coding of sweet, bitter, and umami tastes: different receptor cells sharing similar signaling pathways}, Volume = {112}, Year = {2003}, url = {papers/Zhang_Cell2003.pdf}} @article{Sekar:2016, Abstract = {Schizophrenia is a heritable brain illness with unknown pathogenic mechanisms. Schizophrenia's strongest genetic association at a population level involves variation in the major histocompatibility complex (MHC) locus, but the genes and molecular mechanisms accounting for this have been challenging to identify. Here we show that this association arises in part from many structurally diverse alleles of the complement component 4 (C4) genes. We found that these alleles generated widely varying levels of C4A and C4B expression in the brain, with each common C4 allele associating with schizophrenia in proportion to its tendency to generate greater expression of C4A. Human C4 protein localized to neuronal synapses, dendrites, axons, and cell bodies. In mice, C4 mediated synapse elimination during postnatal development. These results implicate excessive complement activity in the development of schizophrenia and may help explain the reduced numbers of synapses in the brains of individuals with schizophrenia.}, Author = {Sekar, Aswin and Bialas, Allison R and de Rivera, Heather and Davis, Avery and Hammond, Timothy R and Kamitaki, Nolan and Tooley, Katherine and Presumey, Jessy and Baum, Matthew and Van Doren, Vanessa and Genovese, Giulio and Rose, Samuel A and Handsaker, Robert E and {Schizophrenia Working Group of the Psychiatric Genomics Consortium} and Daly, Mark J and Carroll, Michael C and Stevens, Beth and McCarroll, Steven A}, Date-Added = {2016-01-29 22:14:49 +0000}, Date-Modified = {2016-01-29 22:14:49 +0000}, Doi = {10.1038/nature16549}, Journal = {Nature}, Journal-Full = {Nature}, Month = {Jan}, pmid = {26814963}, Pst = {aheadofprint}, Title = {Schizophrenia risk from complex variation of complement component 4}, Year = {2016}, url = {papers/Sekar_Nature2016.pdf}} @article{Azevedo:2009, Abstract = {The human brain is often considered to be the most cognitively capable among mammalian brains and to be much larger than expected for a mammal of our body size. Although the number of neurons is generally assumed to be a determinant of computational power, and despite the widespread quotes that the human brain contains 100 billion neurons and ten times more glial cells, the absolute number of neurons and glial cells in the human brain remains unknown. Here we determine these numbers by using the isotropic fractionator and compare them with the expected values for a human-sized primate. We find that the adult male human brain contains on average 86.1 +/- 8.1 billion NeuN-positive cells ("neurons") and 84.6 +/- 9.8 billion NeuN-negative ("nonneuronal") cells. With only 19% of all neurons located in the cerebral cortex, greater cortical size (representing 82% of total brain mass) in humans compared with other primates does not reflect an increased relative number of cortical neurons. The ratios between glial cells and neurons in the human brain structures are similar to those found in other primates, and their numbers of cells match those expected for a primate of human proportions. These findings challenge the common view that humans stand out from other primates in their brain composition and indicate that, with regard to numbers of neuronal and nonneuronal cells, the human brain is an isometrically scaled-up primate brain.}, Author = {Azevedo, Frederico A C and Carvalho, Ludmila R B and Grinberg, Lea T and Farfel, Jos{\'e} Marcelo and Ferretti, Renata E L and Leite, Renata E P and Jacob Filho, Wilson and Lent, Roberto and Herculano-Houzel, Suzana}, Date-Added = {2016-01-19 23:38:02 +0000}, Date-Modified = {2016-01-19 23:38:02 +0000}, Doi = {10.1002/cne.21974}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Aged; Antigens, Nuclear; Brain; Cerebral Cortex; Humans; Immunohistochemistry; Male; Middle Aged; Nerve Tissue Proteins; Neuroglia; Neurons}, Month = {Apr}, Number = {5}, Pages = {532-41}, pmid = {19226510}, Pst = {ppublish}, Title = {Equal numbers of neuronal and nonneuronal cells make the human brain an isometrically scaled-up primate brain}, Volume = {513}, Year = {2009}, url = {papers/Azevedo_JCompNeurol2009.pdf}} @article{Llinas:2012, Author = {Llin{\'a}s, Rodolfo and Sugimori, Mutsuyuki}, Date-Added = {2016-01-13 18:53:15 +0000}, Date-Modified = {2016-01-13 18:53:15 +0000}, Journal = {Cerebellum}, Journal-Full = {Cerebellum (London, England)}, Mesh = {Animals; Cerebellum; Dendrites; Electrophysiological Phenomena; Electrophysiology; Humans; Purkinje Cells; Tetrodotoxin}, Month = {Sep}, Number = {3}, Pages = {612-28}, pmid = {23035258}, Pst = {ppublish}, Title = {Probing the functional properties of mammalian dendrites. 1980}, Volume = {11}, Year = {2012}} @article{Llinas:1980a, Abstract = {1. Intradendritic recordings from Purkinje cells in vitro indicate that white matter stimulation produces large synaptic responses by the activation of the climbing fibre afferent, but antidromic potentials do not actively invade the dendritic tree. 2. Climbing fibre responses may be reversed in a manner similar to that observed at the somatic level. However, the reversal does not show the biphasicity often seen at somatic level. 3. Input resistance of these dendrites was found to range from 15 to 30 M omega. The non-linear properties seen at the somatic level for depolarizing currents are also encountered here. However, there seems to be less anomalous rectification. 4. Detailed analysis of repetitive firing of Purkinje cells elicited by outward DC current shows that, as in the case of the antidromic invasion, the fast somatic potentials (s.s.) do not invade the dendrite actively. However, the dendritic spike bursts (d.s.b.s) interposed between the s.s. potentials are most prominent at dendritic level. 5. Two types of voltage-dependent Ca responses were observed. At low stimulus level a plateau-like depolarization is accompanied by a prominent conductance change; further depolarization produces large dendritic action potentials. These two classes of response are TTX-resistant but are blocked by Cd, Co, Mn or D600, or by the removal of extracellular Ca. 6. Following blockage of the Ca conductance, plateau potentials produced by a non-inactivating Na conductance are observed mainly near the soma indicating that this voltage-dependent conductance is probably associated with the somatic membrane. 7. Spontaneous firing in Purkinje cell dendrites is very similar to that observed at the soma. However, the amplitude of these bursts is larger at dendritic level. It is further concluded that these TTX-insensitive spikes are generated at multiple sites along the dendritic tree. 8. Six ionic conductances seem to be involved in Purkinje cell electroresponsiveness: (a) an inactivating and (b) a non-inactivating Na conductance at or near the soma, (c) a spike- and (d) a plateau-generating Ca conductance, and (e) voltage-dependent and (f) Ca-dependent K currents. 9. The possible role of these conductances in Purkinje cell integration is discussed.}, Author = {Llin{\'a}s, R and Sugimori, M}, Date-Added = {2016-01-13 18:53:12 +0000}, Date-Modified = {2016-01-13 18:53:12 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Action Potentials; Animals; Calcium; Dendrites; Electric Conductivity; Guinea Pigs; In Vitro Techniques; Membrane Potentials; Neurons, Afferent; Purkinje Cells; Sodium; Synapses}, Month = {Aug}, Pages = {197-213}, Pmc = {PMC1282967}, pmid = {7441553}, Pst = {ppublish}, Title = {Electrophysiological properties of in vitro Purkinje cell dendrites in mammalian cerebellar slices}, Volume = {305}, Year = {1980}} @article{Llinas:1980, Abstract = {1. The electrical activity of Purkinje cells was studied in guinea-pig cerebellar slices in vitro. Intracellular recordings from Purkinje cell somata were obtained under direct vision, and antidromic, synaptic and direct electroresponsiveness was demonstrated. Synaptic potentials produced by the activation of the climbing fibre afferent could be reversed by direct membrane depolarization. 2. Input resistance of impaled neurones ranged from 10 to 19 M omega and demonstrated non-linearities in both hyperpolarizing and depolarizing directions. 3. Direct activation of a Purkinje cell indicated that repetitive firing of fast somatic spikes (s.s.) occurs, after a threshold, with a minimum spike frequency of about 30 spikes/sec, resembling the '2-class' response of crab nerve (Hodgkin, 1948). 4. As the amplitude of the stimulus was increased, a second form of electroresponsiveness characterized by depolarizing spike bursts (d.s.b.) was observed and was often accomppanied by momentary inactivation of the s.s. potentials. Upon application of tetrodotoxin (TTX) or removal of Na+ ions from the superfusion fluid, the s.s. potentials were abolished while the burst responses remained intact. However, Ca conductance blockers such as Co, Cd, Mn and D600, or the replacement of Ca by Mg, completely abolish d.s.b.s. 5. If Ca conductance was blocked, or Ca removed from the superfusion fluid without blockage of Na conductance, two types of Na-dependent electroresponsiveness were seen: (a) the s.s. potentials and (b) slow rising all-or-none responses which reached plateau at approximately -15 mV and could last for several seconds. These all-or-none Na-dependent plateau depolarizations outlasted the stimulus and were accompanied by a large increase in membrane conductance. Within certain limits the rate of rise and amplitude of the plateau were independent of stimulus strength. The latency, however, was shortened as stimulus amplitude was increased. These potentials were blocked by TTX or by Na-free solutions. 6. Substitution of extracellular Ca by Ba or intracellular injection of tetraethylammonium generated prolonged action potentials lasting for several seconds and showing a plateau more ositive than those obtained in norrmal circumstances by either non-inactivating Na or Ca currents. 7. Spontaneous firing of the Purkinje cell was characterized by burst-like activity consisting of both s.s. and d.s.b. responses. Addition of TTX to the bath left the basic spontaneous activity and its frequency unaltered, indicating tha Ca spiking and Ca-dependent K conductance changes are the main events underlying this oscillatory behaviour. 8...}, Author = {Llin{\'a}s, R and Sugimori, M}, Date-Added = {2016-01-13 18:53:07 +0000}, Date-Modified = {2016-01-13 18:53:07 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Action Potentials; Animals; Barium; Calcium; Electric Conductivity; Guinea Pigs; In Vitro Techniques; Membrane Potentials; Purkinje Cells; Sodium; Synapses; Tetraethylammonium Compounds}, Month = {Aug}, Pages = {171-95}, Pmc = {PMC1282966}, pmid = {7441552}, Pst = {ppublish}, Title = {Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices}, Volume = {305}, Year = {1980}} @article{Jan:1976, Abstract = {The anatomy and physiology of the Drosophila larval neuromuscular junction were studied. 2. The dependence of muscle resting potentials on [K+]o and [Na+]o follows the Goldman-Hodgkin-Katz equation (PNa/PK=0-23). Chloride ions distribute passively across the membrane. 3. The mean specific membrane resistance of muscle fibres is 4-3 X 10(3) omega cm2, and the mean specific membrane capacitance is 7-1 muF/cm2. The muscle fibre is virtually isopotential. 4. Transmitter release is quantal. Both the miniature excitatory junctional potential and the evoked release follow the Poisson distribution. 5. Transmitter release depends on approximately the fourth power of [Ca2+]o. If Sr2+ replaces Ca2+, it depends on approximately the fourth power of [Sr2+]o. Mg2+ reduces transmitter release without altering the fourth power dependence on [Ca2+]o.}, Author = {Jan, L Y and Jan, Y N}, Date-Added = {2016-01-13 18:52:38 +0000}, Date-Modified = {2016-01-13 18:52:38 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Animals; Calcium; Chlorides; Drosophila melanogaster; Hydrogen-Ion Concentration; Larva; Magnesium; Membrane Potentials; Neuromuscular Junction; Osmolar Concentration; Potassium; Sodium; Strontium; Synaptic Transmission}, Month = {Oct}, Number = {1}, Pages = {189-214}, Pmc = {PMC1307637}, pmid = {11339}, Pst = {ppublish}, Title = {Properties of the larval neuromuscular junction in Drosophila melanogaster}, Volume = {262}, Year = {1976}} @article{Katz:1967, Abstract = {1. The axo-axonic giant synapse in the stellate ganglion of the squid has been used to study synaptic transmission.2. When nerve impulses have been eliminated with tetrodotoxin, synaptic transfer of potential changes can still be obtained by applying brief depolarizing pulses to the presynaptic terminal.3. Suitably matched pulses are as effective as the normal presynaptic spike in evoking post-synaptic potentials. The synaptic delay and the time course of the post-synaptic potential are very similar to that in the normal preparation.4. The synaptic transfer (input/output) characteristic has been studied under different experimental conditions. With brief (1-2 msec) current pulses, post-synaptic response becomes detectable when the presynaptic depolarization exceeds about 30 mV. The post-synaptic potential increases about tenfold with 10 mV increments of presynaptic depolarization.5. Calcium increases, magnesium reduces the slope of the synaptic transfer curve. The influences on this curve of (i) duration of the pulse, (ii) preceding level of membrane potential, (iii) position of recording electrode, (iv) rate of repetitive stimulation are described.6. After loading the synaptic terminal with tetraethylammonium ions, large inside-positive potentials can be produced in the terminal and maintained for many milliseconds.7. By raising the internal potential to a sufficiently high level, synaptic transfer becomes suppressed during the pulse, and the post-synaptic response is delayed until the end of the pulse.8. This observation is in accord with a prediction of the ;calcium hypothesis', viz. that inward movement of a positively charged Ca compound, or of the calcium ion itself, constitutes one of the essential links in the ;electro-secretory' coupling process of the axon terminal.}, Author = {Katz, B and Miledi, R}, Date-Added = {2016-01-13 18:51:22 +0000}, Date-Modified = {2016-01-13 18:51:22 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Mesh = {Action Potentials; Animals; Axons; Calcium; Electric Stimulation; In Vitro Techniques; Iontophoresis; Mollusca; Neuromuscular Junction; Neurotransmitter Agents; Stellate Ganglion; Synapses; Synaptic Transmission; Tetraethylammonium Compounds; Tetrodotoxin}, Month = {Sep}, Number = {2}, Pages = {407-36}, Pmc = {PMC1365564}, pmid = {4383089}, Pst = {ppublish}, Title = {A study of synaptic transmission in the absence of nerve impulses}, Volume = {192}, Year = {1967}} @article{Coombs:1955, Author = {Coombs, J S and Eccles, J C and Fatt, P}, Date-Added = {2016-01-13 18:50:41 +0000}, Date-Modified = {2016-10-20 17:00:12 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {neurons; GABA; receptor; Ion Channel Gating; neurophysiology; voltage-clamp}, Mesh = {Neurons; Synaptic Potentials}, Month = {Nov}, Number = {2}, Pages = {326-74}, Pmc = {PMC1363415}, pmid = {13278905}, Pst = {ppublish}, Title = {The specific ionic conductances and the ionic movements across the motoneuronal membrane that produce the inhibitory post-synaptic potential}, Volume = {130}, Year = {1955}, url = {papers/Coombs_JPhysiol1955.pdf}} @article{Fatt:1953, Author = {Fatt, P and Katz, B}, Date-Added = {2016-01-13 18:50:05 +0000}, Date-Modified = {2016-10-20 17:41:24 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {MUSCLES/physiology; SHELLFISH}, Mesh = {Animals; Mollusca; Muscles; Shellfish}, Month = {Apr}, Number = {1-2}, Pages = {171-204}, Pmc = {PMC1366030}, pmid = {13062231}, Pst = {ppublish}, Title = {The electrical properties of crustacean muscle fibres}, Volume = {120}, Year = {1953}, url = {papers/Fatt_JPhysiol1953.pdf}} @article{Hodgkin:1952e, Author = {Hodgkin, A L and Huxley, A F}, Date-Added = {2016-01-13 18:12:26 +0000}, Date-Modified = {2016-01-13 18:14:55 +0000}, Journal = {Proc R Soc Lond B Biol Sci}, Journal-Full = {Proceedings of the Royal Society of London. Series B, Biological sciences}, Keywords = {AXONS}, Mesh = {Axons; Nerve Fibers}, Month = {Oct}, Number = {899}, Pages = {177-83}, pmid = {13003922}, Pst = {ppublish}, Title = {Propagation of electrical signals along giant nerve fibers}, Volume = {140}, Year = {1952}} @article{Hodgkin:1952d, Author = {Hodgkin, A L and Huxley, A F}, Date-Added = {2016-01-13 18:12:24 +0000}, Date-Modified = {2016-01-13 18:14:48 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {AXONS}, Mesh = {Axons; Humans}, Month = {Aug}, Number = {4}, Pages = {500-44}, Pmc = {PMC1392413}, pmid = {12991237}, Pst = {ppublish}, Title = {A quantitative description of membrane current and its application to conduction and excitation in nerve}, Volume = {117}, Year = {1952}, url = {papers/Hodgkin_JPhysiol1952a.pdf}} @article{Hodgkin:1952c, Author = {Hodgkin, A L and Huxley, A F}, Date-Added = {2016-01-13 18:12:23 +0000}, Date-Modified = {2016-01-13 18:14:41 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {AXONS; SODIUM/effects}, Mesh = {Animals; Axons; Ions; Loligo; Membrane Potentials; Sodium; Sodium, Dietary}, Month = {Apr}, Number = {4}, Pages = {497-506}, Pmc = {PMC1392212}, pmid = {14946715}, Pst = {ppublish}, Title = {The dual effect of membrane potential on sodium conductance in the giant axon of Loligo}, Volume = {116}, Year = {1952}, url = {papers/Hodgkin_JPhysiol1952b.pdf}} @article{Hodgkin:1952b, Author = {Hodgkin, A L and Huxley, A F}, Date-Added = {2016-01-13 18:12:21 +0000}, Date-Modified = {2016-01-13 18:14:34 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {AXONS}, Mesh = {Animals; Axons; Humans; Loligo}, Month = {Apr}, Number = {4}, Pages = {473-96}, Pmc = {PMC1392209}, pmid = {14946714}, Pst = {ppublish}, Title = {The components of membrane conductance in the giant axon of Loligo}, Volume = {116}, Year = {1952}, url = {papers/Hodgkin_JPhysiol1952c.pdf}} @article{Hodgkin:1952a, Author = {Hodgkin, A L and Huxley, A F}, Date-Added = {2016-01-13 18:12:19 +0000}, Date-Modified = {2016-01-13 18:14:28 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {AXONS; POTASSIUM/effects; SODIUM/effects}, Mesh = {Animals; Axons; Ions; Loligo; Potassium; Sodium; Sodium, Dietary}, Month = {Apr}, Number = {4}, Pages = {449-72}, Pmc = {PMC1392213}, pmid = {14946713}, Pst = {ppublish}, Title = {Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo}, Volume = {116}, Year = {1952}, url = {papers/Hodgkin_JPhysiol1952d.pdf}} @article{Hodgkin:1952, Author = {Hodgkin, A L and Huxley, A F and Katz, B}, Date-Added = {2016-01-13 18:12:18 +0000}, Date-Modified = {2016-01-13 18:14:20 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {AXONS}, Mesh = {Animals; Axons; Loligo}, Month = {Apr}, Number = {4}, Pages = {424-48}, Pmc = {PMC1392219}, pmid = {14946712}, Pst = {ppublish}, Title = {Measurement of current-voltage relations in the membrane of the giant axon of Loligo}, Volume = {116}, Year = {1952}, url = {papers/Hodgkin_JPhysiol1952.pdf}} @article{Hodgkin:1939, Author = {Hodgkin, A L and Huxley, A F}, Date-Added = {2016-01-11 19:48:09 +0000}, Date-Modified = {2016-01-11 19:50:53 +0000}, Doi = {10.1038/144710a0}, Journal = {Nature}, Keywords = {Action Potentials; squid giant axon; neurophysiology; Classical/physiology}, Pages = {710-711}, Title = {Action Potentials Recorded from Inside a Nerve Fibre}, Volume = {144}, Year = {1939}, url = {papers/Hodgkin_Nature1939.pdf}} @article{Hodgkin:1949b, Author = {Hodgkin, A L and Katz, B}, Date-Added = {2016-01-11 19:19:06 +0000}, Date-Modified = {2016-01-11 19:19:53 +0000}, Journal = {J Exp Biol}, Journal-Full = {The Journal of experimental biology}, Keywords = {NERVOUS SYSTEM}, Mesh = {Axons; Calcium; Calcium, Dietary; Nerve Fibers; Nervous System}, Month = {Oct}, Number = {3}, Pages = {292-4, pl}, pmid = {15395900}, Pst = {ppublish}, Title = {The effect of calcium on the axoplasm of giant nerve fibers}, Volume = {26}, Year = {1949}} @article{Hodgkin:1949a, Author = {Hodgkin, A L and Katz, B}, Date-Added = {2016-01-11 19:18:58 +0000}, Date-Modified = {2016-01-11 19:20:07 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {NERVOUS SYSTEM}, Mesh = {Animals; Axons; Decapodiformes; Nervous System; Temperature}, Month = {Aug}, Number = {1-2}, Pages = {240-9}, Pmc = {PMC1392577}, pmid = {15394322}, Pst = {ppublish}, Title = {The effect of temperature on the electrical activity of the giant axon of the squid}, Volume = {109}, Year = {1949}} @article{Hodgkin:1949, Author = {Hodgkin, A L and Katz, B}, Date-Added = {2016-01-11 19:18:07 +0000}, Date-Modified = {2016-01-11 19:20:21 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {NEURONS; SODIUM}, Mesh = {Animals; Axons; Decapodiformes; Ions; Neurons; Sodium; Sodium, Dietary}, Month = {Mar}, Number = {1}, Pages = {37-77}, Pmc = {PMC1392331}, pmid = {18128147}, Pst = {ppublish}, Title = {The effect of sodium ions on the electrical activity of giant axon of the squid}, Volume = {108}, Year = {1949}, url = {papers/HODGKIN_JPhysiol1949.pdf}} @article{Root:2014, Abstract = {The lateral habenula (LHb) is involved in reward, aversion, addiction and depression through descending interactions with several brain structures, including the ventral tegmental area (VTA). The VTA provides reciprocal inputs to LHb, but their actions are unclear. Here we show that the majority of rat and mouse VTA neurons innervating LHb coexpress markers for both glutamate signaling (vesicular glutamate transporter 2; VGluT2) and GABA signaling (glutamic acid decarboxylase; GAD, and vesicular GABA transporter; VGaT). A single axon from these mesohabenular neurons coexpresses VGluT2 protein and VGaT protein and, surprisingly, establishes symmetric and asymmetric synapses on LHb neurons. In LHb slices, light activation of mesohabenular fibers expressing channelrhodopsin2 driven by VGluT2 (Slc17a6) or VGaT (Slc32a1) promoters elicits release of both glutamate and GABA onto single LHb neurons. In vivo light activation of mesohabenular terminals inhibits or excites LHb neurons. Our findings reveal an unanticipated type of VTA neuron that cotransmits glutamate and GABA and provides the majority of mesohabenular inputs.}, Author = {Root, David H and Mejias-Aponte, Carlos A and Zhang, Shiliang and Wang, Hui-Ling and Hoffman, Alexander F and Lupica, Carl R and Morales, Marisela}, Date-Added = {2016-01-07 20:54:13 +0000}, Date-Modified = {2016-01-07 20:54:13 +0000}, Doi = {10.1038/nn.3823}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Animals; Axons; Glutamic Acid; Habenula; Male; Neural Pathways; Rats, Sprague-Dawley; Reward; Synapses; Ventral Tegmental Area; Vesicular Glutamate Transport Protein 2; gamma-Aminobutyric Acid}, Month = {Nov}, Number = {11}, Pages = {1543-51}, pmid = {25242304}, Pst = {ppublish}, Title = {Single rodent mesohabenular axons release glutamate and GABA}, Volume = {17}, Year = {2014}, url = {papers/Root_NatNeurosci2014.pdf}, Bdsk-File-2 = {papers/Root_NatNeurosci2014a.pdf}} @article{Pei:2015, Abstract = {Direction selectivity of direction-selective ganglion cells (DSGCs) in the retina results from patterned excitatory and inhibitory inputs onto DSGCs during motion stimuli. The inhibitory inputs onto DSGCs are directionally tuned to the antipreferred (null) direction and therefore potently suppress spiking during motion in the null direction. However, whether direction-selective inhibition is indispensable for direction selectivity is unclear. Here, we selectively eliminated the directional tuning of inhibitory inputs onto DSGCs by disrupting GABA release from the presynaptic interneuron starburst amacrine cell in the mouse retina. We found that, even without directionally tuned inhibition, direction selectivity can still be implemented in a subset of On-Off DSGCs by direction-selective excitation and a temporal offset between excitation and isotropic inhibition. Our results therefore demonstrate the concerted action of multiple synaptic mechanisms for robust direction selectivity in the retina. Significance statement: The direction-selective circuit in the retina has been a classic model to study neural computations by the brain. An important but unresolved question is how direction selectivity is implemented by directionally tuned excitatory and inhibitory mechanisms. Here we specifically removed the direction tuning of inhibition from the circuit. We found that direction tuning of inhibition is important but not indispensable for direction selectivity of DSGCs' spiking activity, and that the residual direction selectivity is implemented by direction-selective excitation and temporal offset between excitation and inhibition. Our results highlight the concerted actions of synaptic excitation and inhibition required for robust direction selectivity in the retina and provide critical insights into how patterned excitation and inhibition collectively implement sensory processing.}, Author = {Pei, Zhe and Chen, Qiang and Koren, David and Giammarinaro, Benno and Acaron Ledesma, Hector and Wei, Wei}, Date-Added = {2015-12-15 18:44:22 +0000}, Date-Modified = {2015-12-15 18:44:22 +0000}, Doi = {10.1523/JNEUROSCI.0933-15.2015}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {direction selectivity; retina; starburst amacrine cell; synaptic excitation; synaptic inhibition; vesicular GABA transporter}, Month = {Sep}, Number = {38}, Pages = {13219-32}, Pmc = {PMC4579379}, pmid = {26400950}, Pst = {ppublish}, Title = {Conditional Knock-Out of Vesicular GABA Transporter Gene from Starburst Amacrine Cells Reveals the Contributions of Multiple Synaptic Mechanisms Underlying Direction Selectivity in the Retina}, Volume = {35}, Year = {2015}, url = {papers/Pei_JNeurosci2015.pdf}} @article{Catania:2002, Abstract = {We investigated naked mole-rat somatosensory cortex to determine how brain areas are modified in mammals with unusual and extreme sensory specializations. Naked mole-rats (Heterocephalus glaber) have numerous anatomical specializations for a subterranean existence, including rows of sensory hairs along the body and tail, reduced eyes, and ears sensitive to low frequencies. However, chief among their adaptations are behaviorally important, enlarged incisors permanently exterior to the oral cavity that are used for digging, object manipulation, social interactions, and feeding. Here we report an extraordinary brain organization where nearly one-third (31%) of primary somatosensory cortex is devoted to the representations of the upper and lower incisors. In addition, somatosensory cortex is greatly enlarged (as a proportion of total neocortical area) compared with closely related laboratory rats. Finally, somatosensory cortex in naked mole-rats encompasses virtually all of the neocortex normally devoted to vision. These findings indicate that major cortical remodeling has occurred in naked mole-rats, paralleling the anatomical and behavioral specializations related to fossorial life.}, Author = {Catania, Kenneth C and Remple, Michael S}, Date-Added = {2015-12-14 01:08:16 +0000}, Date-Modified = {2015-12-14 01:08:16 +0000}, Doi = {10.1073/pnas.072097999}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Brain; Brain Mapping; Models, Anatomic; Mole Rats; Rats; Rats, Long-Evans; Somatosensory Cortex; Tooth; Touch}, Month = {Apr}, Number = {8}, Pages = {5692-7}, Pmc = {PMC122833}, pmid = {11943853}, Pst = {ppublish}, Title = {Somatosensory cortex dominated by the representation of teeth in the naked mole-rat brain}, Volume = {99}, Year = {2002}, url = {papers/Catania_ProcNatlAcadSciUSA2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.072097999}} @article{Crish:2006, Abstract = {Naked mole-rats are fossorial rodents native to eastern Africa that spend their lives in extensive subterranean burrows where visual cues are poor. Not surprisingly, they have a degenerated eye and optic nerve, suggesting they have poor visual abilities. However, little is known about their central visual system. To investigate the organization of their central visual system, we injected a neuronal tracer into the eyes of naked mole-rats and mice to compare the neural structures mediating vision. We found that the superior colliculus and lateral geniculate nucleus were severely atrophied in the naked mole-rat. The olivary pretectal nucleus was reduced but still retained its characteristic morphology, possibly indicating a role in light detection. In addition, the suprachiasmatic nucleus is well innervated and resembles the same structure in other rodents. The naked mole-rat appears to have selectively lost structures that mediate form vision while retaining structures needed for minimal entrainment of circadian rhythms. Similar results have been reported for other mole-rat species. Taken together, these data suggest that light detection may still play an important role in the lives of these "blind" animals: most likely for circadian entrainment or setting seasonal rhythms.}, Author = {Crish, Samuel D and Dengler-Crish, Christine M and Catania, Kenneth C}, Date-Added = {2015-12-14 01:06:27 +0000}, Date-Modified = {2015-12-14 01:06:27 +0000}, Doi = {10.1002/ar.a.20288}, Journal = {Anat Rec A Discov Mol Cell Evol Biol}, Journal-Full = {The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology}, Mesh = {Adaptation, Ocular; Animals; Eye; Female; Male; Mice; Mice, Inbred C57BL; Mole Rats; Ocular Physiological Phenomena; Rats; Superior Colliculi; Vision, Ocular; Visual Pathways}, Month = {Feb}, Number = {2}, Pages = {205-12}, pmid = {16419086}, Pst = {ppublish}, Title = {Central visual system of the naked mole-rat (Heterocephalus glaber)}, Volume = {288}, Year = {2006}, url = {papers/Crish_AnatRecADiscovMolCellEvolBiol2006.pdf}} @article{Guertin:2009, Abstract = {At the beginning of the 20th century, Thomas Graham Brown conducted experiments that after a long hiatus changed views on the neural control of locomotion. His seminal work supported by subsequent evidence generated largely from the 1960s onwards showed that across species walking, flying, and swimming are controlled largely by a neuronal network that has been referred to as the central pattern generator (CPG) for locomotion. In mammals, this caudally localized spinal cord network was found to generate the basic command signals sent to muscles of the limbs for locomotor rhythm and pattern generation. This article constitutes a comprehensive review summarizing key findings on the organization and properties of this network.}, Author = {Guertin, Pierre A}, Date-Added = {2015-12-12 00:27:55 +0000}, Date-Modified = {2015-12-12 00:28:57 +0000}, Doi = {10.1016/j.brainresrev.2009.08.002}, Journal = {Brain Res Rev}, Journal-Full = {Brain research reviews}, Keywords = {Locomotion; behavior; Swimming; SPINAL CORD; rat; rodent, development}, Mesh = {Animals; Brain; Humans; Locomotion; Models, Neurological; Nerve Net; Neurons; Spinal Cord}, Month = {Dec}, Number = {1}, Pages = {45-56}, pmid = {19720083}, Pst = {ppublish}, Title = {The mammalian central pattern generator for locomotion}, Volume = {62}, Year = {2009}, url = {papers/Guertin_BrainResRev2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainresrev.2009.08.002}} @article{Nishimaru:2000, Abstract = {It is well known that in the neonatal rat spinal cord preparation, alternating rhythmic bursts in the left and right ventral roots in a given lumbar segment can be induced by bath-application of N-methyl-D-aspartate or 5-hydroxytryptamine. Alternation between L2 and L5 ventral roots on the same side, representing the activity of flexor and extensor muscles, respectively, can be observed as well. In the prenatal period in the rat, alternation between the left and right ventral roots is established between embryonic day (E) 16.5 and E18.5. The alternation between the L2 and L5 ventral roots emerges at E20.5. Recent findings show that locomotor-like rhythmic activity with similar characteristics can be induced in the neonatal mouse preparation. In the lumbar spinal cord in the neonatal mouse, it is likely that the rhythm-generating network is distributed throughout the lumbar region with a rostro-caudal gradient, a situation similar to that in the neonatal and fetal rat spinal cord. With this review we hope to highlight the dramatic changes that neuronal networks generating locomotor-like activity undergo during the prenatal development of the rat. Moreover, the distribution of the neuronal network generating the locomotor rhythm in the neonatal rat and mouse spinal cord is compared.}, Author = {Nishimaru, H and Kudo, N}, Date-Added = {2015-12-11 23:40:58 +0000}, Date-Modified = {2015-12-11 23:41:08 +0000}, Journal = {Brain Res Bull}, Journal-Full = {Brain research bulletin}, Keywords = {Locomotion; behavior; Swimming; SPINAL CORD; rat; rodent; development}, Mesh = {Animals; Animals, Newborn; Embryo, Mammalian; In Vitro Techniques; Locomotion; Lumbar Vertebrae; Mice; Nerve Net; Periodicity; Rats; Spinal Cord}, Month = {Nov}, Number = {5}, Pages = {661-9}, pmid = {11165801}, Pst = {ppublish}, Title = {Formation of the central pattern generator for locomotion in the rat and mouse}, Volume = {53}, Year = {2000}, url = {papers/Nishimaru_BrainResBull2000.pdf}} @article{Clarac:1992, Abstract = {In studies of central nervous system networks, it is synaptic transmission to the postsynaptic soma-dendritic membrane that has received the most attention, in particular in relation to the analysis of sensory-motor integration. Sensory transmission is gated during ongoing movements in both invertebrates and vertebrates, such that it may be depressed in one phase of a cyclic movement and facilitated in another, in order to optimize the execution of the ongoing motor task. This presynaptic modulation is not limited to sensory afferents, but also occurs in synapses of both excitatory and inhibitory premotor interneurons. The modulation can be mediated by the release of different transmitters at axo-axonal synapses, which activate different types of receptors. In addition, presynaptic sensory axons can be coupled via gap junctions, which under certain conditions may mediate a presynaptic facilitation.}, Author = {Clarac, F and el Manira, A and Cattaert, D}, Date-Added = {2015-12-11 23:39:02 +0000}, Date-Modified = {2015-12-11 23:39:58 +0000}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Locomotion; behavior; Swimming; SPINAL CORD; rat; rodent}, Mesh = {Action Potentials; Afferent Pathways; Animals; Astacoidea; Cats; Chloride Channels; Electric Stimulation; GTP-Binding Proteins; Ion Channel Gating; Locomotion; Membrane Proteins; Models, Neurological; Motor Activity; Receptors, GABA-A; Sensation; Signal Transduction; Synaptic Transmission}, Month = {Dec}, Number = {6}, Pages = {764-9}, pmid = {1335811}, Pst = {ppublish}, Title = {Presynaptic control as a mechanism of sensory-motor integration}, Volume = {2}, Year = {1992}} @article{Cazalets:1992, Abstract = {1. The role of serotonin (5-HT) and excitatory amino-acids (EAAs) in the activation of the neural networks (i.e. the central pattern generators) that organize locomotion in mammals was investigated in an isolated brainstem-spinal cord preparation from the newborn rat. 2. The neuroactive substances were bath applied and the activity of fictive locomotion was recorded in the ventral roots. 3. Serotonin initiated an alternating pattern of right and left action potential bursts. The period of this rhythm was dose dependent, i.e. it decreased from around 10 s at 2 x 10(-5) M to 5 s at 10(-4) M. The effects of serotonin were blocked by a 5-HT1 antagonist (propranolol) and by 5-HT2 antagonists (ketanserin, cyproheptadine, mianserin). 5-HT3 antagonists were ineffective. The effects of methoxytryptamine, a non-selective 5-HT agonist, mimicked the 5-HT effects. 4. The endogenous EAAs, glutamate and aspartate, also triggered an alternating rhythmic pattern. Their effects were blocked by 2-amino-5-phosphonovaleric acid (AP-5; a N-methyl-D-aspartate (NMDA) receptor blocker) and 6,7-dinitro-quinoxaline-2,3-dione (a non-NMDA receptor blocker). 5. Several EAA agonists (N-methyl-D,L-aspartate (NMA) and kainate) initiated rhythmic activity. The period of the induced rhythm (from 3 to 1 s) was similar with both of these substances but in a range of concentrations which was ten times lower in the case of kainate (10(-6) to 5 x 10(-6) M) than in that of NMA (10(-5) to 4 x 10(-5) M). alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate and quisqualate occasionally triggered some episodes of fictive locomotion with a threshold at 6 x 10(-7) and 10(-5) M, respectively.}, Author = {Cazalets, J R and Sqalli-Houssaini, Y and Clarac, F}, Date-Added = {2015-12-11 23:39:00 +0000}, Date-Modified = {2015-12-11 23:39:52 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {Locomotion; behavior; Swimming; SPINAL CORD; rat; rodent}, Mesh = {Action Potentials; Animals; Animals, Newborn; Aspartic Acid; Brain Stem; Dose-Response Relationship, Drug; Glutamates; Glutamic Acid; Kainic Acid; Locomotion; N-Methylaspartate; Nerve Net; Quisqualic Acid; Rats; Rats, Wistar; Serotonin; Spinal Cord}, Month = {Sep}, Pages = {187-204}, Pmc = {PMC1175639}, pmid = {1362441}, Pst = {ppublish}, Title = {Activation of the central pattern generators for locomotion by serotonin and excitatory amino acids in neonatal rat}, Volume = {455}, Year = {1992}, url = {papers/Cazalets_JPhysiol1992.pdf}} @article{Cazalets:1990, Abstract = {Swimming behaviour was studied in neonate rats by carrying out electromyographic recordings. The study showed that the early swimming pattern was characterized by highly instable temporal parameters. A decrease was found to occur with age in the variability of the instantaneous period in each leg and in that of the antiphase pattern. Moreover, a dissociation occurred during development between the foreleg and the backleg activity. While patterns involving the forelegs always remained extremely instable, a considerable improvement was found to occur with time in the hindlimb activity.}, Author = {Cazalets, J R and Menard, I and Cr{\'e}mieux, J and Clarac, F}, Date-Added = {2015-12-11 23:36:28 +0000}, Date-Modified = {2015-12-11 23:38:04 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Keywords = {Locomotion; rat; rodent; behavior; Swimming; development}, Mesh = {Afferent Pathways; Animals; Animals, Newborn; Central Nervous System; Electromyography; Forelimb; Hindlimb; Locomotion; Motor Activity; Muscle Contraction; Muscles; Neuromuscular Junction; Rats; Rats, Inbred Strains; Reaction Time; Swimming}, Month = {Nov}, Number = {3}, Pages = {215-25}, pmid = {2285479}, Pst = {ppublish}, Title = {Variability as a characteristic of immature motor systems: an electromyographic study of swimming in the newborn rat}, Volume = {40}, Year = {1990}, url = {papers/Cazalets_BehavBrainRes1990.pdf}} @article{Newsome:1985, Abstract = {Physiological experiments have produced evidence that the middle temporal visual area (MT) of the monkey is selectively involved in the analysis of visual motion. We tested this hypothesis by studying the effects of small chemical lesions of MT on eye movements made in response to moving as opposed to stationary visual targets. We observed two deficits for eye movements made to moving targets: a monkey's ability to match the speed of his smooth pursuit eye movements to the speed of the moving target was impaired, and a monkey's ability to adjust the amplitude of a saccadic eye movement to compensate for target motion was impaired. In contrast, saccades to stationary targets were unaffected by the MT lesions, suggesting that monkeys with MT lesions had more difficulty responding to moving than to stationary stimuli. These results provide the first behavioral evidence that neural processing in MT contributes to the cortical analysis of visual motion.}, Author = {Newsome, W T and Wurtz, R H and D{\"u}rsteler, M R and Mikami, A}, Date-Added = {2015-11-18 03:11:53 +0000}, Date-Modified = {2015-11-18 03:12:33 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {visual system; Neocortex; monkey; function; behavior; topographic map; vision; Motion Perception}, Mesh = {Animals; Cerebral Cortex; Female; Ibotenic Acid; Macaca mulatta; Motion Perception; Oxazoles; Psychomotor Performance; Saccades; Temporal Lobe; Visual Perception}, Month = {Mar}, Number = {3}, Pages = {825-40}, pmid = {3973698}, Pst = {ppublish}, Title = {Deficits in visual motion processing following ibotenic acid lesions of the middle temporal visual area of the macaque monkey}, Volume = {5}, Year = {1985}} @article{Zhu:2015, Abstract = {Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer drugs) which can precisely control three major GPCR signaling pathways (Gq, Gi, and Gs). DREADD technology has been successfully applied in a variety of in vivo studies to control GPCR signaling, and here we describe recent advances of DREADD technology and discuss its potential application in drug discovery, gene therapy, and tissue engineering.}, Author = {Zhu, Hu and Roth, Bryan L}, Date-Added = {2015-11-17 21:44:18 +0000}, Date-Modified = {2015-11-17 21:44:42 +0000}, Doi = {10.1093/ijnp/pyu007}, Journal = {Int J Neuropsychopharmacol}, Journal-Full = {The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)}, Keywords = {GPCRs; GsD; chemogenetics; hM3Dq; hM4Di; DREADD; activity manipulation; Methods}, Mesh = {Animals; Genetic Techniques; Humans; Neurons; Receptors, G-Protein-Coupled; Signal Transduction}, Month = {Jan}, Number = {1}, Pmc = {PMC4368861}, pmid = {25522378}, Pst = {epublish}, Title = {DREADD: a chemogenetic GPCR signaling platform}, Volume = {18}, Year = {2015}, url = {papers/Zhu_IntJNeuropsychopharmacol2015.pdf}} @article{Armbruster:2007, Abstract = {We evolved muscarinic receptors in yeast to generate a family of G protein-coupled receptors (GPCRs) that are activated solely by a pharmacologically inert drug-like and bioavailable compound (clozapine-N-oxide). Subsequent screening in human cell lines facilitated the creation of a family of muscarinic acetylcholine GPCRs suitable for in vitro and in situ studies. We subsequently created lines of telomerase-immortalized human pulmonary artery smooth muscle cells stably expressing all five family members and found that each one faithfully recapitulated the signaling phenotype of the parent receptor. We also expressed a G(i)-coupled designer receptor in hippocampal neurons (hM(4)D) and demonstrated its ability to induce membrane hyperpolarization and neuronal silencing. We have thus devised a facile approach for designing families of GPCRs with engineered ligand specificities. Such reverse-engineered GPCRs will prove to be powerful tools for selectively modulating signal-transduction pathways in vitro and in vivo.}, Author = {Armbruster, Blaine N and Li, Xiang and Pausch, Mark H and Herlitze, Stefan and Roth, Bryan L}, Date-Added = {2015-11-17 21:39:57 +0000}, Date-Modified = {2015-11-17 21:40:42 +0000}, Doi = {10.1073/pnas.0700293104}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Methods; Grants; activity manipulation; DREADD}, Mesh = {Animals; Cell Line, Transformed; Clozapine; Designer Drugs; Epitopes; Evolution, Molecular; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Hippocampus; Humans; Hydrolysis; Ligands; Models, Molecular; Mutant Proteins; Myocytes, Smooth Muscle; Neurons; Phosphatidylinositols; Protein Engineering; Pulmonary Artery; Rats; Receptor, Muscarinic M3; Receptor, Muscarinic M4; Receptors, G-Protein-Coupled; Saccharomyces cerevisiae}, Month = {Mar}, Number = {12}, Pages = {5163-8}, Pmc = {PMC1829280}, pmid = {17360345}, Pst = {ppublish}, Title = {Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand}, Volume = {104}, Year = {2007}, url = {papers/Armbruster_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0700293104}} @article{Rogan:2011, Abstract = {A significant challenge for neuroscientists is to determine how both electrical and chemical signals affect the activity of cells and circuits and how the nervous system subsequently translates that activity into behavior. Remote, bidirectional manipulation of those signals with high spatiotemporal precision is an ideal approach to addressing that challenge. Neuroscientists have recently developed a diverse set of tools that permit such experimental manipulation with varying degrees of spatial, temporal, and directional control. These tools use light, peptides, and small molecules to primarily activate ion channels and G protein-coupled receptors (GPCRs) that in turn activate or inhibit neuronal firing. By monitoring the electrophysiological, biochemical, and behavioral effects of such activation/inhibition, researchers can better understand the links between brain activity and behavior. Here, we review the tools that are available for this type of experimentation. We describe the development of the tools and highlight exciting in vivo data. We focus primarily on designer GPCRs (receptors activated solely by synthetic ligands, designer receptors exclusively activated by designer drugs) and microbial opsins (e.g., channelrhodopsin-2, halorhodopsin, Volvox carteri channelrhodopsin) but also describe other novel techniques that use orthogonal receptors, caged ligands, allosteric modulators, and other approaches. These tools differ in the direction of their effect (activation/inhibition, hyperpolarization/depolarization), their onset and offset kinetics (milliseconds/minutes/hours), the degree of spatial resolution they afford, and their invasiveness. Although none of these tools is perfect, each has advantages and disadvantages, which we describe, and they are all still works in progress. We conclude with suggestions for improving upon the existing tools.}, Author = {Rogan, Sarah C and Roth, Bryan L}, Date-Added = {2015-11-17 21:38:18 +0000}, Date-Modified = {2015-11-17 21:38:42 +0000}, Doi = {10.1124/pr.110.003020}, Journal = {Pharmacol Rev}, Journal-Full = {Pharmacological reviews}, Keywords = {Methods; Grants; activity manipulation; DREADD}, Mesh = {Animals; Designer Drugs; Humans; Ligands; Light; Neurons; Opsins; Peptides; Receptors, G-Protein-Coupled; Signal Transduction}, Month = {Jun}, Number = {2}, Pages = {291-315}, Pmc = {PMC3082452}, pmid = {21415127}, Pst = {ppublish}, Title = {Remote control of neuronal signaling}, Volume = {63}, Year = {2011}, url = {papers/Rogan_PharmacolRev2011.pdf}} @article{Dong:2010, Abstract = {Recently we have perfected a chemical-genetic approach to gain precise spatio-temporal control of cellular signaling. This approach entails the cell-type specific expression of mutant G-protein coupled receptors which have been evolved to be activated by the pharmacologically inert drug-like small molecule clozapine N-oxide. We have named these mutant GPCRs DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). In this paper we will first review recent applications of this technology for the remote control of neuronal and non-neuronal signaling. Next, we will also introduce new variants which could be useful for the control of cellular signaling in discrete cellular compartments. Finally, we will suggest future basic science and therapeutic applications of this general technology.}, Author = {Dong, Shuyun and Allen, John A and Farrell, Martilias and Roth, Bryan L}, Date-Added = {2015-11-17 21:35:01 +0000}, Date-Modified = {2015-11-17 21:37:40 +0000}, Doi = {10.1039/c002568m}, Journal = {Mol Biosyst}, Journal-Full = {Molecular bioSystems}, Keywords = {Methods; Grants; activity manipulation; DREADD}, Mesh = {Animals; Cell Physiological Phenomena; Chemistry Techniques, Analytical; Combinatorial Chemistry Techniques; Genetic Techniques; Growth and Development; Humans; Models, Biological; Organ Specificity; Time Factors}, Month = {Aug}, Number = {8}, Pages = {1376-80}, pmid = {20532295}, Pst = {ppublish}, Title = {A chemical-genetic approach for precise spatio-temporal control of cellular signaling}, Volume = {6}, Year = {2010}, url = {papers/Dong_MolBiosyst2010.pdf}} @article{Vardy:2015, Abstract = {DREADDs are chemogenetic tools widely used to remotely control cellular signaling, neuronal activity, and behavior. Here we used a structure-based approach to develop a new Gi-coupled DREADD using the kappa-opioid receptor as a template (KORD) that is activated by the pharmacologically inert ligand salvinorin B (SALB). Activation of virally expressed KORD in several neuronal contexts robustly attenuated neuronal activity and modified behaviors. Additionally, co-expression of the KORD and the Gq-coupled M3-DREADD within the same neuronal population facilitated the sequential and bidirectional remote control of behavior. The availability of DREADDs activated by different ligands provides enhanced opportunities for investigating diverse physiological systems using multiplexed chemogenetic actuators.}, Author = {Vardy, Eyal and Robinson, J Elliott and Li, Chia and Olsen, Reid H J and DiBerto, Jeffrey F and Giguere, Patrick M and Sassano, Flori M and Huang, Xi-Ping and Zhu, Hu and Urban, Daniel J and White, Kate L and Rittiner, Joseph E and Crowley, Nicole A and Pleil, Kristen E and Mazzone, Christopher M and Mosier, Philip D and Song, Juan and Kash, Thomas L and Malanga, C J and Krashes, Michael J and Roth, Bryan L}, Date-Added = {2015-11-16 19:08:47 +0000}, Date-Modified = {2015-11-16 19:09:21 +0000}, Doi = {10.1016/j.neuron.2015.03.065}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {DREADD; Methods; Grants; activity manipulation}, Mesh = {Animals; Behavior, Animal; Diterpenes; Ligands; Mice, Inbred C57BL; Neurons; Receptors, Opioid, kappa; Signal Transduction}, Month = {May}, Number = {4}, Pages = {936-46}, Pmc = {PMC4441592}, pmid = {25937170}, Pst = {ppublish}, Title = {A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior}, Volume = {86}, Year = {2015}, url = {papers/Vardy_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.03.065}} @article{Robinson:2014, Abstract = {An essential aspect of episodic memory is the formation of associations between neutral sensory cues in the environment. In light of recent evidence that this critical aspect of learning does not require the hippocampus, we tested the involvement of the retrosplenial cortex (RSC) in this process using a chemogenetic approach that allowed us to temporarily silence neurons along the entire rostrocaudal extent of the RSC. A viral vector containing the gene for a synthetic inhibitory G-protein-coupled receptor (hM4Di) was infused into RSC. When the receptor was later activated by systemic injection of clozapine-N-oxide, neural activity in RSC was transiently silenced (confirmed using a patch-clamp procedure). Rats expressing hM4Di and control rats were trained in a sensory preconditioning procedure in which a tone and light were paired on some trials and a white noise stimulus was presented alone on the other trials during the Preconditioning phase. Thus, rats were given the opportunity to form an association between a tone and a light in the absence of reinforcement. Later, the light was paired with food. During the test phase when the auditory cues were presented alone, controls exhibited more conditioned responding during presentation of the tone compared with the white noise reflecting the prior formation of a tone-light association. Silencing RSC neurons during the Preconditioning phase prevented the formation of an association between the tone and light and eliminated the sensory preconditioning effect. These findings indicate that RSC may contribute to episodic memory formation by linking essential sensory stimuli during learning.}, Author = {Robinson, Siobhan and Todd, Travis P and Pasternak, Anna R and Luikart, Bryan W and Skelton, Patrick D and Urban, Daniel J and Bucci, David J}, Date-Added = {2015-11-16 19:04:26 +0000}, Date-Modified = {2015-11-16 19:04:50 +0000}, Doi = {10.1523/JNEUROSCI.1349-14.2014}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {DREADD; episodic; hippocampus; learning; parahippocampal; retrosplenial; activity manipulation; Methods; behavior}, Mesh = {Animals; Association Learning; Cerebral Cortex; Clozapine; Conditioning (Psychology); Cues; Male; Neurons; Rats; Rats, Long-Evans}, Month = {Aug}, Number = {33}, Pages = {10982-8}, Pmc = {PMC4131013}, pmid = {25122898}, Pst = {ppublish}, Title = {Chemogenetic silencing of neurons in retrosplenial cortex disrupts sensory preconditioning}, Volume = {34}, Year = {2014}, url = {papers/Robinson_JNeurosci2014.pdf}} @article{Fotowat:2009, Abstract = {Drosophila melanogaster exhibits a robust escape response to objects approaching on a collision course. Although a pair of large command interneurons called the giant fibers (GFs) have been postulated to trigger such behaviors, their role has not been directly demonstrated. Here, we show that escape from visual stimuli like those generated by approaching predators does not rely on the activation of the GFs and consists of a more complex and less stereotyped motor sequence than that evoked by the GFs. Instead, the timing of escape is tightly correlated with the activity of previously undescribed descending interneurons that signal a threshold angular size of the approaching object. The activity pattern of these interneurons shares features with those of visual escape circuits of several species, including pigeons, frogs, and locusts, and may therefore have evolved under similar constraints. These results show that visually evoked escapes in Drosophila can rely on at least two descending neuronal pathways: the GFs and the novel pathway we characterize electrophysiologically. These pathways exhibit very different patterns of sensory activity and are associated with two distinct motor programs.}, Author = {Fotowat, Haleh and Fayyazuddin, Amir and Bellen, Hugo J and Gabbiani, Fabrizio}, Date-Added = {2015-11-16 17:16:11 +0000}, Date-Modified = {2015-11-16 17:17:12 +0000}, Doi = {10.1152/jn.00073.2009}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {behavior; function; vision; visual system; Drosophila melanogaster; aversive; looming response}, Mesh = {Action Potentials; Animals; Animals, Genetically Modified; Biomechanical Phenomena; Drosophila Proteins; Drosophila melanogaster; Escape Reaction; Interneurons; Lighting; Microelectrodes; Muscles; Mutation; Neural Pathways; Neurons; Photic Stimulation; Psychomotor Performance; Receptors, Nicotinic; Visual Perception}, Month = {Aug}, Number = {2}, Pages = {875-85}, Pmc = {PMC3817277}, pmid = {19474177}, Pst = {ppublish}, Title = {A novel neuronal pathway for visually guided escape in Drosophila melanogaster}, Volume = {102}, Year = {2009}, url = {papers/Fotowat_JNeurophysiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00073.2009}} @article{Ball:1971, Abstract = {Twenty-four infants ranging in age from 2 to 11 weeks responded to symmetrically expanding shadows, which optically specify an approaching object, with an integrated avoidance response and upset. This response did not occur for asymmetrically expanding shadows nor for contracting shadows that specify an object on a miss path and a receding object. The response was observed in all the infants regardless of age, and the addition of kinetic depth information to the displays did not increase the intensity or likelihood of the response. In a second experiment, seven infants defensively reacted to the approach of a real object except when it was on a miss path.}, Author = {Ball, W and Tronick, E}, Date-Added = {2015-11-16 17:11:18 +0000}, Date-Modified = {2015-11-16 17:19:56 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {infant; human; behavior; aversive; vision; visual system; activity-development; looming response}, Mesh = {Avoidance Learning; Distance Perception; Psychology, Child}, Month = {Feb}, Number = {3973}, Pages = {818-20}, pmid = {5541165}, Pst = {ppublish}, Title = {Infant responses to impending collision: optical and real}, Volume = {171}, Year = {1971}} @article{Biagi:2015, Abstract = {In adults, motion perception is mediated by an extensive network of occipital, parietal, temporal, and insular cortical areas. Little is known about the neural substrate of visual motion in infants, although behavioural studies suggest that motion perception is rudimentary at birth and matures steadily over the first few years. Here, by measuring Blood Oxygenated Level Dependent (BOLD) responses to flow versus random-motion stimuli, we demonstrate that the major cortical areas serving motion processing in adults are operative by 7 wk of age. Resting-state correlations demonstrate adult-like functional connectivity between the motion-selective associative areas, but not between primary cortex and temporo-occipital and posterior-insular cortices. Taken together, the results suggest that the development of motion perception may be limited by slow maturation of the subcortical input and of the cortico-cortical connections. In addition they support the existence of independent input to primary (V1) and temporo-occipital (V5/MT+) cortices very early in life.}, Author = {Biagi, Laura and Crespi, Sofia Allegra and Tosetti, Michela and Morrone, Maria Concetta}, Date-Added = {2015-11-15 17:17:08 +0000}, Date-Modified = {2015-11-15 17:22:47 +0000}, Doi = {10.1371/journal.pbio.1002260}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {human; infant; visual system; Visual Cortex; BEHAVIOR; Motion Perception; topographic map; fMRI; connectivity; network analysis; activity-development}, Month = {Sep}, Number = {9}, Pages = {e1002260}, Pmc = {PMC4587790}, pmid = {26418729}, Pst = {epublish}, Title = {BOLD Response Selective to Flow-Motion in Very Young Infants}, Volume = {13}, Year = {2015}, url = {papers/Biagi_PLoSBiol2015.pdf}} @article{Oh:2014, Abstract = {Comprehensive knowledge of the brain's wiring diagram is fundamental for understanding how the nervous system processes information at both local and global scales. However, with the singular exception of the C. elegans microscale connectome, there are no complete connectivity data sets in other species. Here we report a brain-wide, cellular-level, mesoscale connectome for the mouse. The Allen Mouse Brain Connectivity Atlas uses enhanced green fluorescent protein (EGFP)-expressing adeno-associated viral vectors to trace axonal projections from defined regions and cell types, and high-throughput serial two-photon tomography to image the EGFP-labelled axons throughout the brain. This systematic and standardized approach allows spatial registration of individual experiments into a common three dimensional (3D) reference space, resulting in a whole-brain connectivity matrix. A computational model yields insights into connectional strength distribution, symmetry and other network properties. Virtual tractography illustrates 3D topography among interconnected regions. Cortico-thalamic pathway analysis demonstrates segregation and integration of parallel pathways. The Allen Mouse Brain Connectivity Atlas is a freely available, foundational resource for structural and functional investigations into the neural circuits that support behavioural and cognitive processes in health and disease.}, Author = {Oh, Seung Wook and Harris, Julie A and Ng, Lydia and Winslow, Brent and Cain, Nicholas and Mihalas, Stefan and Wang, Quanxin and Lau, Chris and Kuan, Leonard and Henry, Alex M and Mortrud, Marty T and Ouellette, Benjamin and Nguyen, Thuc Nghi and Sorensen, Staci A and Slaughterbeck, Clifford R and Wakeman, Wayne and Li, Yang and Feng, David and Ho, Anh and Nicholas, Eric and Hirokawa, Karla E and Bohn, Phillip and Joines, Kevin M and Peng, Hanchuan and Hawrylycz, Michael J and Phillips, John W and Hohmann, John G and Wohnoutka, Paul and Gerfen, Charles R and Koch, Christof and Bernard, Amy and Dang, Chinh and Jones, Allan R and Zeng, Hongkui}, Date-Added = {2015-11-14 01:08:48 +0000}, Date-Modified = {2015-11-14 01:14:11 +0000}, Doi = {10.1038/nature13186}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {connectivity; Methods; Computational Biology; Graph theory; network; Neocortex; Thalamic Nuclei; topographic map; mouse; Mice}, Mesh = {Animals; Atlases as Topic; Axons; Brain; Cerebral Cortex; Connectome; Corpus Striatum; Male; Mice; Mice, Inbred C57BL; Models, Neurological; Neuroanatomical Tract-Tracing Techniques; Thalamus}, Month = {Apr}, Number = {7495}, Pages = {207-14}, pmid = {24695228}, Pst = {ppublish}, Title = {A mesoscale connectome of the mouse brain}, Volume = {508}, Year = {2014}, url = {papers/Oh_Nature2014.pdf}, Bdsk-File-2 = {papers/Oh_Nature2014a.pdf}} @article{Markowitz:2015, Abstract = {Time-locked sequences of neural activity can be found throughout the vertebrate forebrain in various species and behavioral contexts. From "time cells" in the hippocampus of rodents to cortical activity controlling movement, temporal sequence generation is integral to many forms of learned behavior. However, the mechanisms underlying sequence generation are not well known. Here, we describe a spatial and temporal organization of the songbird premotor cortical microcircuit that supports sparse sequences of neural activity. Multi-channel electrophysiology and calcium imaging reveal that neural activity in premotor cortex is correlated with a length scale of 100 µm. Within this length scale, basal-ganglia-projecting excitatory neurons, on average, fire at a specific phase of a local 30 Hz network rhythm. These results show that premotor cortical activity is inhomogeneous in time and space, and that a mesoscopic dynamical pattern underlies the generation of the neural sequences controlling song.}, Author = {Markowitz, Jeffrey E and Liberti, 3rd, William A and Guitchounts, Grigori and Velho, Tarciso and Lois, Carlos and Gardner, Timothy J}, Date-Added = {2015-11-13 22:57:01 +0000}, Date-Modified = {2015-11-13 22:57:01 +0000}, Doi = {10.1371/journal.pbio.1002158}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Month = {Jun}, Number = {6}, Pages = {e1002158}, Pmc = {PMC4454690}, pmid = {26039895}, Pst = {epublish}, Title = {Mesoscopic patterns of neural activity support songbird cortical sequences}, Volume = {13}, Year = {2015}, url = {papers/Markowitz_PLoSBiol2015.pdf}} @article{Hagihara:2015, Abstract = {Neuronal activity is important for the functional refinement of neuronal circuits in the early visual system. At the level of the cerebral cortex, however, it is still unknown whether the formation of fundamental functions such as orientation selectivity depends on neuronal activity, as it has been difficult to suppress activity throughout development. Using genetic silencing of cortical activity starting before the formation of orientation selectivity, we found that the orientation selectivity of neurons in the mouse visual cortex formed and matured normally despite a strong suppression of both spontaneous and visually evoked activity throughout development. After the orientation selectivity formed, the distribution of the preferred orientations of neurons was reorganized. We found that this process required spontaneous activity, but not visually evoked activity. Thus, the initial formation and maturation of orientation selectivity is largely independent of neuronal activity, and the initial selectivity is subsequently modified depending on neuronal activity.}, Author = {Hagihara, Kenta M and Murakami, Tomonari and Yoshida, Takashi and Tagawa, Yoshiaki and Ohki, Kenichi}, Date-Added = {2015-11-13 22:16:11 +0000}, Date-Modified = {2015-11-13 22:52:04 +0000}, Doi = {10.1038/nn.4155}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {visual system; Visual Cortex; activity manipulation; activity-dependent; activity-development; topographic map; Orientation; direction; mouse; mice; spontaneous activity}, Month = {Nov}, pmid = {26523644}, Pst = {aheadofprint}, Title = {Neuronal activity is not required for the initial formation and maturation of visual selectivity}, Year = {2015}, url = {papers/Hagihara_NatNeurosci2015a.pdf}, Bdsk-File-2 = {papers/Hagihara_NatNeurosci2015.pdf}} @article{Aston-Jones:2013, Abstract = {Optogenetics with microbial opsin genes, and pharmacogenetics with designer receptors, represent potent and versatile experimental modalities that can be integrated with each other as well as with a rich diversity of synergistic methods to provide fundamental opportunities in neuroscience research. The 7th Annual Brain Research Meeting in New Orleans in October 2012, Optogenetics and Pharmacogenetics in Neuronal Function and Dysfunction, brought together leading researchers that have developed and used these tools to explore a wide range of questions in nervous system function and dysfunction. This special issue of Brain Research includes articles by speakers in this meeting and others, which together synthesize and summarize the state of the art for optogenetics and designer receptors. This article is part of a Special Issue entitled Optogenetics (7th BRES).}, Author = {Aston-Jones, Gary and Deisseroth, Karl}, Date-Added = {2015-09-30 19:26:18 +0000}, Date-Modified = {2015-11-16 19:08:04 +0000}, Doi = {10.1016/j.brainres.2013.01.026}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {Methods; technique; activity manipulation; Grants; DREADD}, Mesh = {Animals; Autonomic Pathways; Brain; Cognition; Humans; Motivation; Optogenetics; Pharmacogenetics; Receptors, Cell Surface; Signal Transduction}, Month = {May}, Pages = {1-5}, Pmc = {PMC3663045}, pmid = {23422677}, Pst = {ppublish}, Title = {Recent advances in optogenetics and pharmacogenetics}, Volume = {1511}, Year = {2013}, url = {papers/Aston-Jones_BrainRes2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainres.2013.01.026}} @article{DePuy:2013, Abstract = {The C1 neurons are a nodal point for blood pressure control and other autonomic responses. Here we test whether these rostral ventrolateral medullary catecholaminergic (RVLM-CA) neurons use glutamate as a transmitter in the dorsal motor nucleus of the vagus (DMV). After injecting Cre-dependent adeno-associated virus (AAV2) DIO-Ef1α-channelrhodopsin2(ChR2)-mCherry (AAV2) into the RVLM of dopamine-β-hydroxylase Cre transgenic mice (DβH(Cre/0)), mCherry was detected exclusively in RVLM-CA neurons. Within the DMV >95% mCherry-immunoreactive(ir) axonal varicosities were tyrosine hydroxylase (TH)-ir and the same proportion were vesicular glutamate transporter 2 (VGLUT2)-ir. VGLUT2-mCherry colocalization was virtually absent when AAV2 was injected into the RVLM of DβH(Cre/0);VGLUT2(flox/flox) mice, into the caudal VLM (A1 noradrenergic neuron-rich region) of DβH(Cre/0) mice or into the raphe of ePet(Cre/0) mice. Following injection of AAV2 into RVLM of TH-Cre rats, phenylethanolamine N-methyl transferase and VGLUT2 immunoreactivities were highly colocalized in DMV within EYFP-positive or EYFP-negative axonal varicosities. Ultrastructurally, mCherry terminals from RVLM-CA neurons in DβH(Cre/0) mice made predominantly asymmetric synapses with choline acetyl-transferase-ir DMV neurons. Photostimulation of ChR2-positive axons in DβH(Cre/0) mouse brain slices produced EPSCs in 71% of tested DMV preganglionic neurons (PGNs) but no IPSCs. Photostimulation (20 Hz) activated PGNs up to 8 spikes/s (current-clamp). EPSCs were eliminated by tetrodotoxin, reinstated by 4-aminopyridine, and blocked by ionotropic glutamate receptor blockers. In conclusion, VGLUT2 is expressed by RVLM-CA (C1) neurons in rats and mice regardless of the presence of AAV2, the C1 neurons activate DMV parasympathetic PGNs monosynaptically and this connection uses glutamate as an ionotropic transmitter.}, Author = {DePuy, Seth D and Stornetta, Ruth L and Bochorishvili, Genrieta and Deisseroth, Karl and Witten, Ilana and Coates, Melissa and Guyenet, Patrice G}, Date-Added = {2015-09-30 19:26:14 +0000}, Date-Modified = {2015-09-30 19:26:14 +0000}, Doi = {10.1523/JNEUROSCI.4269-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Excitatory Postsynaptic Potentials; Glutamine; Immunohistochemistry; Medulla Oblongata; Mice; Mice, Transgenic; Neurons; Patch-Clamp Techniques; Synaptic Transmission; Vagus Nerve; Vesicular Glutamate Transport Protein 2}, Month = {Jan}, Number = {4}, Pages = {1486-97}, Pmc = {PMC3727439}, pmid = {23345223}, Pst = {ppublish}, Title = {Glutamatergic neurotransmission between the C1 neurons and the parasympathetic preganglionic neurons of the dorsal motor nucleus of the vagus}, Volume = {33}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4269-12.2013}} @article{Alivisatos:2013, Author = {Alivisatos, A Paul and Chun, Miyoung and Church, George M and Deisseroth, Karl and Donoghue, John P and Greenspan, Ralph J and McEuen, Paul L and Roukes, Michael L and Sejnowski, Terrence J and Weiss, Paul S and Yuste, Rafael}, Date-Added = {2015-09-30 19:26:12 +0000}, Date-Modified = {2015-09-30 19:26:12 +0000}, Doi = {10.1126/science.1236939}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Brain Diseases; Brain Mapping; Hippocampus; Humans; Neural Pathways; Neurons}, Month = {Mar}, Number = {6125}, Pages = {1284-5}, Pmc = {PMC3722427}, pmid = {23470729}, Pst = {ppublish}, Title = {Neuroscience. The brain activity map}, Volume = {339}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1236939}} @article{Gazzaniga:2005, Abstract = {Forty-five years ago, Roger Sperry, Joseph Bogen and I embarked on what are now known as the modern split-brain studies. These experiments opened up new frontiers in brain research and gave rise to much of what we know about hemispheric specialization and integration. The latest developments in split-brain research build on the groundwork laid by those early studies. Split-brain methodology, on its own and in conjunction with neuroimaging, has yielded insights into the remarkable regional specificity of the corpus callosum as well as into the integrative role of the callosum in the perception of causality and in our perception of an integrated sense of self.}, Author = {Gazzaniga, Michael S}, Date-Added = {2015-09-30 00:32:59 +0000}, Date-Modified = {2015-09-30 00:33:45 +0000}, Doi = {10.1038/nrn1723}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {mirror symmetry; hemisphere; hemispherectomy; Corpus Callosum; human; BEHAVIOR; Perception; Perceptual Disorders; sensory map}, Mesh = {Animals; Cerebral Cortex; Corpus Callosum; Dominance, Cerebral; Humans; Neurosciences}, Month = {Aug}, Number = {8}, Pages = {653-9}, pmid = {16062172}, Pst = {ppublish}, Title = {Forty-five years of split-brain research and still going strong}, Volume = {6}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1723}} @article{Burbridge:2014, Abstract = {The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial, largely due to the inherent difficulty recording neural activity in early development. Here, we describe genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a decoupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience.}, Author = {Burbridge, Timothy J and Xu, Hong-Ping and Ackman, James B and Ge, Xinxin and Zhang, Yueyi and Ye, Mei-Jun and Zhou, Z Jimmy and Xu, Jian and Contractor, Anis and Crair, Michael C}, Date-Added = {2015-09-04 20:43:26 +0000}, Date-Modified = {2015-09-04 20:43:26 +0000}, Doi = {10.1016/j.neuron.2014.10.051}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Action Potentials; Age Factors; Analysis of Variance; Animals; Animals, Newborn; Calcium; Cyclic AMP; Cyclic GMP; Cyclooxygenase Inhibitors; Eye Proteins; Functional Laterality; Homeodomain Proteins; In Vitro Techniques; Meclofenamic Acid; Mice; Mice, Transgenic; Paired Box Transcription Factors; RNA, Messenger; Receptors, Nicotinic; Repressor Proteins; Retina; Retinal Ganglion Cells; Visual Pathways}, Month = {Dec}, Number = {5}, Pages = {1049-64}, Pmc = {PMC4258148}, pmid = {25466916}, Pst = {ppublish}, Title = {Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors}, Volume = {84}, Year = {2014}, url = {papers/Burbridge_Neuron2014.pdf}, Bdsk-File-2 = {papers/Burbridge_Neuron2014a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.10.051}} @article{Wefers:2000, Abstract = {Binocular interactions play a prominent role in shaping the axonal arbors of geniculocortical fibers and the arbors of Y cells in the retinogeniculate pathway of the fetal cat. Fiber interactions between the two eyes have also been suggested to regulate the formation of retinal projections to the dorsal lateral geniculate nucleus (dlgn) of the fetal monkey, but whether this reflects structural refinements of retinal arbors has not been established. To address this issue, we quantified the morphologic properties of individual fibers in two macaque monkeys at embryonic day (E) 110 and E121 that had an eye removed at E69 and E61, respectively. Fibers were labeled by DiI crystals into the fixed optic tract and were visualized by confocal microscopy. Three measurements were made: the number of branch points within the axon terminal arbor, the total arborization length, and the incidence of axonal side branches on the preterminal axon within the confines of the geniculate. There were no significant differences with respect to these parameters between the prenatal enucleates and normal monkeys of comparable age. This was the case for retinal fibers innervating the magnocellular and the parvocellular segments of the dlgn. The arbors stemming from the remaining eye were widely distributed in the dlgn, with some terminating in territories normally innervated by the other (enucleated) eye. These results lend support to the hypothesis that the expanded projection from the remaining eye to the lateral geniculate nucleus of the prenatally enucleated monkey is due to the maintenance of a contingent of retinal fibers normally eliminated by ganglion cell death.}, Author = {Wefers, C J and Dehay, C and Berland, M and Kennedy, H and Chalupa, L M}, Date-Added = {2015-09-02 00:40:04 +0000}, Date-Modified = {2015-09-02 00:40:04 +0000}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Axons; Carbocyanines; Cell Size; Dendrites; Eye Enucleation; Fluorescent Dyes; Geniculate Bodies; Macaca fascicularis; Retina; Vision, Binocular; Vision, Monocular; Visual Pathways}, Month = {Nov}, Number = {3}, Pages = {362-9}, pmid = {11054699}, Pst = {ppublish}, Title = {Binocular competition does not regulate retinogeniculate arbor size in fetal monkey}, Volume = {427}, Year = {2000}} @article{Polleux:1998b, Abstract = {In the homozygous (but not the heterozygous) reeler mutant, disruption of neuron migration leads to a major perturbation of the cortical environment that in turn could modify (1) the specification of neuronal fate and (2) the proliferation dynamics of cortical precursors. To investigate these issues, tritiated thymidine injections during cortical neurogenesis were coupled with postnatal injections of a retrograde tracer in the spinal cord to accurately measure the neurogenesis of corticospinal neurons in the heterozygous and homozygous mutant. The homozygous reeler shows (1) strict conservation of area-specific timetables of corticospinal neuron generation; (2) neurons with the appropriate birthdates show an enhanced probability of projecting to the spinal cord; (3) during early stages of corticogenesis, there is a reduced rate of neuron production followed at later stages by an increased rate of neuron production; and (4) these changes in the rate of neuron production were shown to be at least partially attributable to changes in the proportions of differentiative divisions. Taken together, our results show that in the developing cortex, the neurogenesis and specification of a given neuronal phenotype are partially controlled by the postmigratory compartment. On the other hand, neither areal identity nor the chronology of production of layer-specific neuronal phenotype seems to depend on the integrity of the cellular environment.}, Author = {Polleux, F and Dehay, C and Kennedy, H}, Date-Added = {2015-09-02 00:39:57 +0000}, Date-Modified = {2015-09-02 00:39:57 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Afferent Pathways; Animals; Animals, Newborn; Cell Count; Cell Death; Cell Division; Female; Male; Mice; Mice, Inbred BALB C; Mice, Neurologic Mutants; Neocortex; Neurons; Pyramidal Tracts; Somatosensory Cortex; Thymidine; Tritium}, Month = {Dec}, Number = {23}, Pages = {9910-23}, pmid = {9822747}, Pst = {ppublish}, Title = {Neurogenesis and commitment of corticospinal neurons in reeler}, Volume = {18}, Year = {1998}} @article{Snider:1999, Abstract = {In the fetal monkey the projections from the two eyes are initially completely intermingled within the dorsal lateral geniculate nucleus (DLGN) before separating into eye-specific layers (). To assess the cellular basis of this developmental process, we examined the morphological properties of individual retinogeniculate axons in prenatal monkeys of known gestational ages. The period studied spanned the time from when binocular overlap has been reported to be maximum, circa embryonic (E) day 77 through E112, when the segregation process is already largely completed in the caudal portion of the nucleus. Retinogeniculate fibers were labeled by making small deposits of DiI crystals into the fixed optic tract. After adequate time was allowed for diffusion of the tracer, fibers were visualized by confocal microscopy, and morphometric measures were made from photomontages. This revealed that retinogeniculate fibers in the embryonic monkey undergo continuous growth and elaboration during binocular overlap and subsequent segregation. Importantly, very few side-branches were found along the preterminal axon throughout the developmental period studied. Thus, restructuring of retinogeniculate fibers does not underlie the formation of eye-restricted projections in the primate. Rather, the results support the hypothesis that binocular segregation in the embryonic monkey is caused by the loss of retinal fibers that initially innervate inappropriate territories ().}, Author = {Snider, C J and Dehay, C and Berland, M and Kennedy, H and Chalupa, L M}, Date-Added = {2015-09-02 00:39:45 +0000}, Date-Modified = {2015-09-02 00:39:45 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Axons; Embryonic and Fetal Development; Geniculate Bodies; Macaca fascicularis; Microscopy, Confocal; Retina; Vision, Binocular; Visual Pathways}, Month = {Jan}, Number = {1}, Pages = {220-8}, pmid = {9870952}, Pst = {ppublish}, Title = {Prenatal development of retinogeniculate axons in the macaque monkey during segregation of binocular inputs}, Volume = {19}, Year = {1999}} @article{Lukaszewicz:2006, Abstract = {Regionalization of cell cycle kinetics of cortical precursors has been described in nonhuman primates and rodents indicating a fate map of areas as distinct proliferative programs in the germinal zones of the neocortex. It remains to be understood how proliferative gradients during corticogenesis are transcribed into a stepwise function to form adult areal borders. Here we have used the monkey areas 17 and 18, which show striking cytoarchitectonic differences, as a model system for studying how developmental events establish areal boundaries in the adult. We present data indicating that the events that are involved in the formation of a sharp border separating 2 areas involve an orchestration of diverse phenomena including differential rates of proliferation, migration, and tangential expansion.}, Author = {Lukaszewicz, Agn{\`e}s and Cortay, V{\'e}ronique and Giroud, Pascale and Berland, Michel and Smart, Iain and Kennedy, Henry and Dehay, Colette}, Date-Added = {2015-09-02 00:39:23 +0000}, Date-Modified = {2015-09-02 00:39:23 +0000}, Doi = {10.1093/cercor/bhk011}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Body Patterning; Cell Differentiation; Cell Proliferation; Haplorhini; Neocortex; Nerve Net; Neurons; Organogenesis}, Month = {Jul}, Pages = {i26-34}, pmid = {16766704}, Pst = {ppublish}, Title = {The concerted modulation of proliferation and migration contributes to the specification of the cytoarchitecture and dimensions of cortical areas}, Volume = {16 Suppl 1}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhk011}} @article{Markov:2014, Abstract = {Retrograde tracer injections in 29 of the 91 areas of the macaque cerebral cortex revealed 1,615 interareal pathways, a third of which have not previously been reported. A weight index (extrinsic fraction of labeled neurons [FLNe]) was determined for each area-to-area pathway. Newly found projections were weaker on average compared with the known projections; nevertheless, the 2 sets of pathways had extensively overlapping weight distributions. Repeat injections across individuals revealed modest FLNe variability given the range of FLNe values (standard deviation <1 log unit, range 5 log units). The connectivity profile for each area conformed to a lognormal distribution, where a majority of projections are moderate or weak in strength. In the G29 × 29 interareal subgraph, two-thirds of the connections that can exist do exist. Analysis of the smallest set of areas that collects links from all 91 nodes of the G29 × 91 subgraph (dominating set analysis) confirms the dense (66%) structure of the cortical matrix. The G29 × 29 subgraph suggests an unexpectedly high incidence of unidirectional links. The directed and weighted G29 × 91 connectivity matrix for the macaque will be valuable for comparison with connectivity analyses in other species, including humans. It will also inform future modeling studies that explore the regularities of cortical networks.}, Author = {Markov, N T and Ercsey-Ravasz, M M and Ribeiro Gomes, A R and Lamy, C and Magrou, L and Vezoli, J and Misery, P and Falchier, A and Quilodran, R and Gariel, M A and Sallet, J and Gamanut, R and Huissoud, C and Clavagnier, S and Giroud, P and Sappey-Marinier, D and Barone, P and Dehay, C and Toroczkai, Z and Knoblauch, K and Van Essen, D C and Kennedy, H}, Date-Added = {2015-09-02 00:38:54 +0000}, Date-Modified = {2015-09-02 00:38:54 +0000}, Doi = {10.1093/cercor/bhs270}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {connection; cortex; graph; monkey; network}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Diffusion Magnetic Resonance Imaging; Image Processing, Computer-Assisted; Macaca fascicularis; Macaca mulatta; Models, Neurological; Neural Pathways; Neuroimaging; Neuronal Tract-Tracers}, Month = {Jan}, Number = {1}, Pages = {17-36}, Pmc = {PMC3862262}, pmid = {23010748}, Pst = {ppublish}, Title = {A weighted and directed interareal connectivity matrix for macaque cerebral cortex}, Volume = {24}, Year = {2014}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhs270}} @article{Kennedy:2012, Abstract = {Variability of gene expression of cortical precursors may partially reflect the operation of the gene regulatory network and determines the boundaries of the state space within which self-organization of the cortex can unfold. In primates, including humans, the outer subventricular zone, a primate-specific germinal zone, generates a large contingent of the projection neurons participating in the interareal network. The number of projection neurons in individual pathways largely determines the network properties as well as the hierarchical organization of the cortex. Mathematical modeling of cell-cycle kinetics of cortical precursors in the germinal zones reveals how multiple control loops ensure the generation of precise numbers of different categories of projection neurons and allow partial simulation of cortical self-organization. We show that molecular manipulation of the cell cycle of cortical precursors shifts the trajectory of the cortical precursor within its state space, increases the diversity in the cortical lineage tree, and explores changes in phylogenetic complexity. These results explore how self-organization underlies the complexity of the cortex and suggest evolutionary mechanisms.}, Author = {Kennedy, Henry and Dehay, Colette}, Date-Added = {2015-09-02 00:38:45 +0000}, Date-Modified = {2015-09-02 00:38:45 +0000}, Doi = {10.1016/B978-0-444-53860-4.00016-7}, Journal = {Prog Brain Res}, Journal-Full = {Progress in brain research}, Mesh = {Animals; Biological Evolution; Cell Cycle; Cerebral Cortex; Humans; Nerve Net; Neurons; Primates}, Pages = {341-60}, pmid = {22230635}, Pst = {ppublish}, Title = {Self-organization and interareal networks in the primate cortex}, Volume = {195}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/B978-0-444-53860-4.00016-7}} @article{Kennedy:2007, Abstract = {The primate neocortex is characterized by a highly expanded supragranular layer (SGL). The interareal connectivity of the neurons in the SLG largely determines the cortical hierarchy that constrains information flow through the cortex. Interareal connectivity is made by precise numbers of connections, raising the possibility that the physiology of a target area is dictated by the numbers of connections and hierarchical distance in each of the pathways that it receives. The developmental mechanisms ensuring the precision of these interareal networks is in part determined by (i) the numbers of SGL neurons generated by the OSVZ, a primate-specific germinal zone. Neuron generation rate in the OSVZ is determined by regulation of the G1 phase of the cell-cycle. This regulation is area-specific and is linked to thalamic projections to the OSVZ; (ii) Prolonged pre- and postnatal pruning of connections originating from the SGL when the infant monkey visually explores its environment. Remodelling serves to sharpen initial patterns of connections and establishes the adult hierarchy. These results suggest that primate cortical networks underlying high-level function undergo prolonged self-organization via regressive phenomena in the cortical plate (axon elimination) and progressive phenomena (directed growth of cortical axons).}, Author = {Kennedy, Henry and Douglas, Rodney and Knoblauch, Kenneth and Dehay, Colette}, Date-Added = {2015-09-02 00:38:36 +0000}, Date-Modified = {2015-09-02 00:38:36 +0000}, Journal = {Novartis Found Symp}, Journal-Full = {Novartis Foundation symposium}, Mesh = {Animals; Body Patterning; Cerebral Cortex; Embryo, Mammalian; Models, Biological; Models, Neurological; Nerve Net; Neural Pathways; Neurons; Primates}, Pages = {178-94 discussion 195-8, 276-81}, pmid = {18494259}, Pst = {ppublish}, Title = {Self-organization and pattern formation in primate cortical networks}, Volume = {288}, Year = {2007}} @article{Dehay:2007, Abstract = {The spatio-temporal timing of the last round of mitosis, followed by the migration of neuroblasts to the cortical plate leads to the formation of the six-layered cortex that is subdivided into functionally defined cortical areas. Whereas many of the cellular and molecular mechanisms have been established in rodents, there are a number of unique features that require further elucidation in primates. Recent findings both in rodents and in primates indicate that regulation of the cell cycle, specifically of the G1 phase has a crucial role in controlling area-specific rates of neuron production and the generation of cytoarchitectonic maps.}, Author = {Dehay, Colette and Kennedy, Henry}, Date-Added = {2015-09-02 00:38:28 +0000}, Date-Modified = {2015-09-02 00:38:28 +0000}, Doi = {10.1038/nrn2097}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Animals; Cell Communication; Cell Cycle; Cell Cycle Proteins; Cell Differentiation; Cell Proliferation; Cerebral Cortex; G1 Phase; Humans; Neurons; Signal Transduction; Stem Cells}, Month = {Jun}, Number = {6}, Pages = {438-50}, pmid = {17514197}, Pst = {ppublish}, Title = {Cell-cycle control and cortical development}, Volume = {8}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2097}} @article{Molnar:2006a, Abstract = {This review aims to provide examples of how both comparative and genetic analyses contribute to our understanding of the rules for cortical development and evolution. Genetic studies have helped us to realize the evolutionary rules of telencephalic organization in vertebrates. The control of the establishment of conserved telencephalic subdivisions and the formation of boundaries between these subdivisions has been examined and the very specific alterations at the striatocortical junction have been revealed. Comparative studies and genetic analyses both demonstrate the differential origin and migratory pattern of the two basic neuron types of the cerebral cortex. GABAergic interneurons are mostly generated in the subpallium and a common mechanism governs their migration to the dorsal cortex in both mammals and sauropsids. The pyramidal neurons are generated within the cortical germinal zone and migrate radially, the earliest generated cell layers comprising preplate cells. Reelin-positive Cajal-Retzius cells are a general feature of all vertebrates studied so far; however, there is a considerable amplification of the Reelin signalling with cortical complexity, which might have contributed to the establishment of the basic mammalian pattern of cortical development. Based on numerous recent observations we shall present the argument that specialization of the mitotic compartments may constitute a major drive behind the evolution of the mammalian cortex. Comparative developmental studies have revealed distinct features in the early compartments of the developing macaque brain, drawing our attention to the limitations of some of the current model systems for understanding human developmental abnormalities of the cortex. Comparative and genetic aspects of cortical development both reveal the workings of evolution.}, Author = {Moln{\'a}r, Zolt{\'a}n and M{\'e}tin, Christine and Stoykova, Anastassia and Tarabykin, Victor and Price, David J and Francis, Fiona and Meyer, Gundela and Dehay, Colette and Kennedy, Henry}, Date-Added = {2015-09-02 00:38:22 +0000}, Date-Modified = {2015-09-02 00:38:22 +0000}, Doi = {10.1111/j.1460-9568.2006.04611.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Mesh = {Animals; Biological Evolution; Cell Differentiation; Cerebral Cortex; Humans; Models, Neurological; Neurons}, Month = {Feb}, Number = {4}, Pages = {921-34}, Pmc = {PMC1931431}, pmid = {16519657}, Pst = {ppublish}, Title = {Comparative aspects of cerebral cortical development}, Volume = {23}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.04611.x}} @article{Dehay:1996a, Abstract = {Prenatal bilateral enucleation induces cortex, which normally would have become striate cortex, to follow a default developmental pathway and to take on the cytoarchitectonic appearance of extrastriate cortex (default extrastriate cortex, Dehay et al. [1996] J. Comp. Neurol. 367:70-89). We have investigated if this manipulation influences the cortical expression of acetylcholinesterase (AChE) and cytochrome oxidase (CO). Early enucleation (before embryonic day 81; E81) had only minor effects on the distribution of AChE and CO in the striate cortex. In animals that underwent operation, the striate cortex CO blobs were significantly more closely spaced on the operculum compared with the calcarine. After early enucleation, there was a periodic distribution of CO dense patches in default extrastriate cortex. These CO patches had a center-to-center spacing that was considerably smaller than that of CO stripes in normal area V2, but was somewhat larger than that of the CO blobs in striate cortex. Although the CO stripes characteristic of normal area V2 could not be detected, there were some high-frequency CO patches, similar to those found in default extrastriate cortex. Early enucleation caused a failure to form the transient AChE bands running perpendicular to the striate border, which are normally present in the fetus and early neonate. Late enucleation did not alter AChE expression in extrastriate cortex. The relatively minor effects of early enucleation in the reduced striate cortex contrast with the changes in expression of these enzymes in extrastriate cortex, which accompany large shifts in the location of the striate border. This suggests a massive reorganisation of cortical phenotype in extrastriate cortex.}, Author = {Dehay, C and Giroud, P and Berland, M and Killackey, H P and Kennedy, H}, Date-Added = {2015-09-02 00:38:12 +0000}, Date-Modified = {2015-09-02 00:38:12 +0000}, Doi = {10.1002/(SICI)1096-9861(19961216)376:3\<386::AID-CNE3\>3.0.CO;2-Z}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Acetylcholinesterase; Animals; Electron Transport Complex IV; Eye Enucleation; Female; Macaca; Neuronal Plasticity; Phenotype; Pregnancy; Vision, Monocular; Visual Cortex}, Month = {Dec}, Number = {3}, Pages = {386-402}, pmid = {8956106}, Pst = {ppublish}, Title = {Phenotypic characterisation of respecified visual cortex subsequent to prenatal enucleation in the monkey: development of acetylcholinesterase and cytochrome oxidase patterns}, Volume = {376}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1096-9861(19961216)376:3%5C<386::AID-CNE3%5C>3.0.CO;2-Z}} @article{Barone:1996, Abstract = {In experiments combining retrograde tracers and histochemistry, we have looked at the prenatal development of the cortical pathway linking areas V2 and V4. Transient expression of acetylcholinesterase in fetal area V2 reveals the separate compartments that project to V4 (temporal directed pathway) and V5 (parietal directed pathway). During early stages of pathway formation, V2 neurons projecting to area V4 are clustered in the appropriate compartments. During the phase of rapid axonal growth, there is a selective increase of connections originating from the appropriate compartments leading to a strongly clustered organization at the peak of connectivity. During this phase, injections involving the white matter also showed clustering, but this was somewhat reduced in comparison to that of gray matter injections. The growth phase is followed by an elimination phase during which there is a tendency for a preferential loss of intercluster connections, which may sharpen the early formed pattern. These results demonstrate the primary role of axonal guidance and target recognition mechanisms followed by a limited extent of selective elimination during the formation of functional cortical pathways in the primate isocortex. Compared to previous findings, these results suggest that the developmental restriction of callosal connections is not a universal model of cortical development. In the present report, the directed growth and early specification of feed-forward connections contrast with the prolonged remodelling of monkey feedback projections, suggesting two distinct developmental strategies of pathway formation in the monkey.}, Author = {Barone, P and Dehay, C and Berland, M and Kennedy, H}, Date-Added = {2015-09-02 00:38:04 +0000}, Date-Modified = {2015-09-02 00:38:04 +0000}, Doi = {10.1002/(SICI)1096-9861(19961007)374:1\<1::AID-CNE1\>3.0.CO;2-7}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Acetylcholinesterase; Animals; Animals, Newborn; Electron Transport Complex IV; Embryonic and Fetal Development; Macaca fascicularis; Microinjections; Neural Pathways; Neurons; Visual Cortex}, Month = {Oct}, Number = {1}, Pages = {1-20}, pmid = {8891943}, Pst = {ppublish}, Title = {Role of directed growth and target selection in the formation of cortical pathways: prenatal development of the projection of area V2 to area V4 in the monkey}, Volume = {374}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1096-9861(19961007)374:1%5C<1::AID-CNE1%5C>3.0.CO;2-7}} @article{Dehay:1996, Abstract = {Bilateral enucleation was performed at different fetal ages during corticogenesis, and the brains were prepared for histological examination. Early-enucleated fetuses (operated prior to embryonic day 77) showed morphological changes at the level of the thalamus and the cortex. In the thalamus, there was a loss of lamination and a decrease in size of the lateral geniculate nucleus. There was a decrease in the size of the inferior pulvinar, but there was no change in the lateral pulvinar. The border of striate cortex was as sharp in the enucleates as it was in the normal monkeys. In three of the four early enucleates, we observed an interdigitation of striate and extrastriate cortex. In three of the early enucleates, we observed a small island of nonstriate cortex near the striate border that was surrounded entirely by striate cortex. Enucleation led to an age-related reduction of striate cortex. This reduction was greater in the operculum than in the calcarine fissure. The reduction of striate cortex was accompanied by an increase in the dimensions of extrastriate visual cortex, so that the overall dimensions of the neocortex remained invariant. The extrastriate cortex in the enucleated animals presented a uniform cytoarchitecture and was indistinguishable from area 18 in the normal animal. There were changes in the gyral pattern that were restricted mainly to the cortex on the operculum. A deepening of minor dimples as well as the induction of a variable number of supplementary sulci led to an increase in the convolution of the occipital lobe. These results are discussed with respect to the specification of cortical areas. They demonstrate that the reduction in striate cortex was not accompanied by an equivalent reduction in the neocortex; rather, there was a border shift, and a large volume of cortex that was destined to become striate cortex appears to be cytoarchitectonically normal extrastriate cortex.}, Author = {Dehay, C and Giroud, P and Berland, M and Killackey, H and Kennedy, H}, Date-Added = {2015-09-02 00:37:46 +0000}, Date-Modified = {2015-09-02 00:37:46 +0000}, Doi = {10.1002/(SICI)1096-9861(19960325)367:1\<70::AID-CNE6\>3.0.CO;2-G}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Aging; Animals; Animals, Newborn; Eye Enucleation; Fetus; Macaca fascicularis; Neuronal Plasticity; Thalamus; Visual Cortex}, Month = {Mar}, Number = {1}, Pages = {70-89}, pmid = {8867284}, Pst = {ppublish}, Title = {Contribution of thalamic input to the specification of cytoarchitectonic cortical fields in the primate: effects of bilateral enucleation in the fetal monkey on the boundaries, dimensions, and gyrification of striate and extrastriate cortex}, Volume = {367}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1096-9861(19960325)367:1%5C<70::AID-CNE6%5C>3.0.CO;2-G}} @article{Barone:1995, Abstract = {The pre- and postnatal developmental changes of the cortical afferents to area 17 were studied in the macaque monkey. Paired injections of the retrograde tracers fast blue and diamidino yellow were made in area 17. Quantitative techniques were used to examine the spatial patterns of labeling in three distinct locations of the extrastriate cortex that correspond to known visual areas. In the adult, each cortical region has a characteristic laminar distribution. In the fetus the proportion of supragranular layer neurons in all cortical regions was much higher than in the adult. The present study shows that despite the very high levels of labeled supragranular layer neurons, there is some early areal specialization so that the adult configuration does not emerge from a uniform distribution. The developmental decline in the proportion of labeled supragranular neurons is complete by 1 month after birth. Each injection of tracer gave rise in each cortical area to dense labeling in a restricted region (projection zone). Areal measurements of projection zones in the supra- and infragranular layers showed that the developmental decrease in the proportion of labeled supragranular layer neurons is accompanied by a relative change of the dimensions of supra- and infragranular projection zones: the supragranular projection zone in the fetus is larger than the infragranular projection zone and vice versa in the adult. In the fetus, the two projection zones corresponding to each of the two tracers overlap in the supragranular layers whereas they are largely separated in the infragranular layers. During development there is a progressive decrease in the overlap of the supragranular projection zones and an increase in the overlap in the infragranular layers. Again, the adult configuration is achieved 1 month after birth. This developmental inversion of the areal dimensions of the projection zones in supra- and infragranular layers is accompanied by a drastic decrease in the proportion of double-labeled neurons located in supragranular layers. These results clearly show that early in development, axonal projections to area V1 are modified in very different ways according to whether they originate from supra- or infragranular layers. This developmental process lasts for about 80 d. These findings show that in the primate there is a prolonged remodeling of axonal projections that is a highly characteristic feature of this species.}, Author = {Barone, P and Dehay, C and Berland, M and Bullier, J and Kennedy, H}, Date = {1995 Jan-Feb}, Date-Added = {2015-09-02 00:37:36 +0000}, Date-Modified = {2015-09-02 00:37:36 +0000}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Amidines; Animals; Animals, Newborn; Axons; Female; Fluorescent Dyes; Histocytochemistry; Macaca fascicularis; Neural Pathways; Neurons, Afferent; Pregnancy; Visual Cortex; Visual Pathways}, Number = {1}, Pages = {22-38}, pmid = {7719128}, Pst = {ppublish}, Title = {Developmental remodeling of primate visual cortical pathways}, Volume = {5}, Year = {1995}} @article{Meissirel:1993, Abstract = {Anterograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was used to study transient axons from the visual cortex in the pyramidal tract. Injections at birth restricted to the visual cortex labeled axons in the vicinity of the pontine nuclei. Two to eight days after birth, axons from the occipital cortex were found posterior to the pontine nucleus, their caudalmost stable target. Transient corticospinal axons from the presumptive primary visual cortex did not grow caudal to the pyramidal decussation. Innervation of more distal targets preceded innervation of proximal targets. Innervation of the pontine nucleus is initiated around 68 hours after birth, when the transient extension in the medullary pyramidal tract has attained its maximum caudal extent. Innervation of the superior colliculus begins 9 days after birth. Retrograde tracers were used to follow the developmental changes in the cortical distribution of the parent neurons giving rise to axons in the pyramidal tract. In the adult, labeled neurons following injection of retrograde tracer in the pyramidal tract occupied less than a third of the neocortex and were centred on the anterior part of the coronal and spleniocruciate gyri. In the immature brain, labeled neurons covered more than two-thirds of the neocortex. Areal density measurements in the neonate showed that peak labeling was centred in the anterior coronal and spleniocruciate gyri, where corticospinal cells in the adult are located. There was a marked rostral-caudal gradient so that labeled neurons were very scarce towards the occipital pole. These results, showing transient neocortical axons in the pyramidal tract in a carnivore, suggest that this may be a common feature of mammalian development. The finding that the adult pattern of corticospinal projections does not emerge from a uniform distribution is discussed with respect to the areal specification of cortical connectivity.}, Author = {Meissirel, C and Dehay, C and Kennedy, H}, Date-Added = {2015-09-02 00:37:28 +0000}, Date-Modified = {2015-09-02 00:37:28 +0000}, Doi = {10.1002/cne.903380205}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Animals, Newborn; Ferrets; Neural Pathways; Occipital Lobe; Pons; Pyramidal Tracts; Time Factors; Visual Cortex}, Month = {Dec}, Number = {2}, Pages = {193-213}, pmid = {8308167}, Pst = {ppublish}, Title = {Transient cortical pathways in the pyramidal tract of the neonatal ferret}, Volume = {338}, Year = {1993}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903380205}} @article{Dehay:1993, Abstract = {An as-yet unresolved issue in developmental neurobiology is whether the discrete areas that form the mammalian cortex emerge from a uniform cortical plate or whether they are already specified in the germinal zone. A feature of the primate striate cortex is that the number of neurons per unit area is twice that of anywhere else in the cerebral cortex. Here we take advantage of this unique structural feature to investigate whether the extra striate cortical cells are due to increased neuron production during neurogenesis. We labelled precursors undergoing terminal cell division with 3H-thymidine and allowed them to migrate to the cortical plate. Cell counts revealed that their rate of production in the germinal zone of striate cortex is higher than in that given rise to extrastriate cortex. Also, we used 3H-thymidine pulse injections to investigate cell cycle dynamics and found that this phase of increased production of striate cortical cells is associated with changes in the parameters of the cell cycle. These results show that cortical area identity is at least partially determined at the level of the ventricular zone.}, Author = {Dehay, C and Giroud, P and Berland, M and Smart, I and Kennedy, H}, Date-Added = {2015-09-02 00:37:21 +0000}, Date-Modified = {2015-09-02 00:37:21 +0000}, Doi = {10.1038/366464a0}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Brain; Cell Cycle; Cell Movement; Embryonic and Fetal Development; Fetus; Macaca fascicularis; Neurons; S Phase; Thymidine; Visual Cortex}, Month = {Dec}, Number = {6454}, Pages = {464-6}, pmid = {8247154}, Pst = {ppublish}, Title = {Modulation of the cell cycle contributes to the parcellation of the primate visual cortex}, Volume = {366}, Year = {1993}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/366464a0}} @article{Kennedy:1990, Author = {Kennedy, H and Dehay, C and Horsburgh, G}, Date-Added = {2015-09-02 00:37:14 +0000}, Date-Modified = {2015-09-02 00:37:14 +0000}, Doi = {10.1038/348494a0}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Electron Transport Complex IV; Primates; Visual Cortex; Visual Perception}, Month = {Dec}, Number = {6301}, Pages = {494}, pmid = {2174128}, Pst = {ppublish}, Title = {Striate cortex periodicity}, Volume = {348}, Year = {1990}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/348494a0}} @article{Kennedy:1993a, Abstract = {Environmental control of gene expression can occur early or late during development, and this is relevant to understanding species differences in cortical specification. Experiments in the developing visual system of the primate show that the areal limits of striate cortex are specified by the thalamic inputs, so that afferent specification of cortex appears as a general feature of mammalian development. Primates differ from nonprimates in that thalamic afferents control very early stages of corticogenesis when symmetrical cell division is forming the pool of striate neuron precursors. Other cortical features are specified much later in primates than in nonprimates. We speculate that the early specification of certain features and the late specification of others contribute to the sophistication of the cerebral cortex characteristic of primates.}, Author = {Kennedy, H and Dehay, C}, Date-Added = {2015-09-02 00:37:09 +0000}, Date-Modified = {2015-09-02 00:37:09 +0000}, Journal = {Perspect Dev Neurobiol}, Journal-Full = {Perspectives on developmental neurobiology}, Mesh = {Afferent Pathways; Animals; Anophthalmos; Cell Differentiation; Cerebral Cortex; Embryonic and Fetal Development; Eye Enucleation; Gene Expression Regulation; Humans; Morphogenesis; Primates; Rodentia; Species Specificity; Thalamus; Time Factors; Visual Cortex}, Number = {2}, Pages = {93-9}, pmid = {8087537}, Pst = {ppublish}, Title = {The importance of developmental timing in cortical specification}, Volume = {1}, Year = {1993}} @article{Kennedy:1993, Abstract = {The developmental basis for the localization of function in the mammalian cortex remains a controversial issue. The newly formed rodent cortex displays a considerable uniformity in terms of its connectivity. This contrasts with the primate, where even the first formed connections can show a high degree of areal specificity. An important clue to understanding these species differences can be obtained by examining how and when the sensory periphery exerts its organizing influence on the developing cortex. In rodents the developmental timetable ensures that the organizational control of the periphery persists late in development, when neurons are forming their first connections. By contrast, in primates the late onset and prolonged duration of corticogenesis result in the periphery being able to exert its influence much earlier, during the phase of precursor proliferation. Differences and similarities between primate and rodent corticogenesis are highly informative. In rodents, recent results with molecular markers show that regional differences in developmental potential exist in the cerebral cortex before innervation from the periphery. Similar findings are predicted in primates. It is to be expected that a more complete understanding of the rules governing the emergence of distinct cortical areas will come from resolving how afferent specification acts within the confines of such regional specializations.}, Author = {Kennedy, H and Dehay, C}, Date = {1993 May-Jun}, Date-Added = {2015-09-02 00:37:04 +0000}, Date-Modified = {2015-09-02 00:37:04 +0000}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Mesh = {Animals; Cerebral Cortex; Humans; Mice; Primates; Rodentia; Species Specificity}, Number = {3}, Pages = {171-86}, pmid = {8324368}, Pst = {ppublish}, Title = {Cortical specification of mice and men}, Volume = {3}, Year = {1993}} @article{Dehay:1988a, Abstract = {Cytochrome oxidase (CytOx) is known to preferentially stain those regions of the visual cortex which receive direct projections from the thalamus. The pattern of CytOx stain has been used to investigate the maturation of thalamic input to areas V1 and V2 in the newborn monkey. In both areas, the intensity of CytOx activity was similar in newborns and adults. The distribution of CytOx in area V2 was not found to vary with age. In area V1, the only difference in CytOx activity in newborns was a relative immaturity of staining in layer 4C. The callosal connections of visual areas V1 and V2 were investigated by the axonal transport of wheat germ agglutinin conjugated to horseradish peroxidase and free horseradish peroxidase. In the adult, V1 was found to be reciprocally callosally connected for a distance of 1-2.5 mm from the V1/V2 border, whilst V2 was connected for a distance of 3-8 mm from the border. In both areas, callosal connections showed a certain degree of clustering, particularly in V2 which contained 97-98% of the total number of callosal connections of these two areas. In the newborn, the number, tangential extent and clustered distribution of callosal connections were as in the adult. In the newborn, as in the adult, callosal connections coincided with regions of high CytOx activity in area V2. The results showing a relative maturity of the tangential distribution of callosal projecting neurons on the one hand, and an immaturity of thalamic projections on the other, are discussed in terms of: (1) the maturational status of the newborn monkey compared to other mammals at the moment of birth and (2) the possible role of visual experience in shaping cortical connections.}, Author = {Dehay, C and Kennedy, H}, Date-Added = {2015-09-02 00:36:55 +0000}, Date-Modified = {2015-09-02 00:36:55 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Mesh = {Aging; Animals; Animals, Newborn; Brain Mapping; Corpus Callosum; Macaca fascicularis; Thalamic Nuclei; Visual Cortex; Visual Pathways}, Month = {Aug}, Number = {3}, Pages = {237-44}, pmid = {3166701}, Pst = {ppublish}, Title = {The maturational status of thalamocortical and callosal connections of visual areas V1 and V2 in the newborn monkey}, Volume = {29}, Year = {1988}} @article{Kennedy:1988, Abstract = {The efferent and afferent connections of the V1/V2 border with the contralateral hemisphere have been examined using anatomical tracers. The V1/V2 border was found to exchange connections with the contralateral V2 area as well as a restricted strip of V1 lying adjacent to the V1/V2 border. Besides these homotopic projections, two heterotopic projections were found to V3/V3A and V5. Anterograde tracing of callosal connections showed that terminals in these heterotopic sites were focused in layer 4, the recipient layer of projections originating from the ipsilateral V1/V2 border. Bilateral injections of fluorescent dyes showed that these heterotopic targets of the V1/V2 border are connected to the homologous ipsilateral V1/V2 border region. The laminar location of callosal projecting neurons as well as their terminals were characteristic for each cortical region. The laminar pattern of callosal connectivity was found to differ markedly from that of associational visual pathways. Two principal hypotheses are suggested by these results. First, the fact that V1 in part is reciprocally callosally connected in all mammals supports the notion that this interhemispheric pathway completes long-range intrinsic cortical connections. Second, the convergence of inter- and intrahemispheric pathways could provide the anatomical basis for the modulation of the sensory processing within one hemisphere by ongoing activity in the contralateral hemisphere.}, Author = {Kennedy, H and Dehay, C}, Date-Added = {2015-09-02 00:36:50 +0000}, Date-Modified = {2015-09-02 00:36:50 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Mesh = {Animals; Brain Mapping; Corpus Callosum; Dominance, Cerebral; Macaca fascicularis; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Aug}, Number = {3}, Pages = {225-36}, pmid = {3166700}, Pst = {ppublish}, Title = {Functional implications of the anatomical organization of the callosal projections of visual areas V1 and V2 in the macaque monkey}, Volume = {29}, Year = {1988}} @article{Dehay:1988, Abstract = {We have examined the anatomical features of ipsilateral transient cortical projections to areas 17, 18, and 19 in the kitten with the use of axonal tracers Fast Blue and WGA-HRP. Injections of tracers in any of the three primary visual areas led to retrograde labeling in frontal, parietal, and temporal cortices. Retrogradely labeled cells were not randomly distributed, but instead occurred preferentially at certain loci. The pattern of retrograde labeling was not influenced by the area injected. The main locus of transiently projecting neurons was an isolated region in the ectosylvian gyrus, probably corresponding to auditory area A1. Other groups of transiently projecting neurons had more variable locations in the frontoparietal cortex. The laminar distribution of neurons sending a transient projection to the visual cortex is characteristic and different from that of parent neurons of other cortical pathways at the same age. In the frontoparietal cortex, transiently projecting neurons were located mainly in layer 1 and the upper part of layers 2 and 3. In the ectosylvian gyrus, nearly all the neurons are located in layers 2 and 3. In addition, a few transiently projecting neurons are found in layer 6 and in the white matter. Transiently projecting neurons have a pyramidal morphology except for the occasional spindle-shaped cell of layer 1 and multipolar cells observed in the white matter. Anterograde studies were used to investigate the location of transient fibers in the visual cortex. Injections of WGA-HRP at the site of origin of transient projections gave rise to few retrogradely labeled cells in areas 17, 18, and 19, demonstrating that transient projections to these areas are not reciprocal. Although labeled axons were found over a wide area of the posterior cortex, they were more numerous over certain regions, including areas 17, 18, and 19, and absent from other more lateral cortical regions. Transient projecting fibers were present in all cortical layers at birth. Plotting the location of transient fibers in numerous sections and at all ages showed that these fibers are not more plentiful in the white matter than they are in the gray matter. We found no evidence that the white/gray matter border constituted a physical barrier to the growth of transient axons. Comparison of the organization of this transient pathway to that of other transient connections is discussed with respect to the development of the cortex.}, Author = {Dehay, C and Kennedy, H and Bullier, J}, Date-Added = {2015-09-02 00:36:44 +0000}, Date-Modified = {2015-09-02 00:36:44 +0000}, Doi = {10.1002/cne.902720106}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Aging; Amidines; Animals; Auditory Cortex; Brain Mapping; Cats; Fluorescent Dyes; Horseradish Peroxidase; Motor Cortex; Neuronal Plasticity; Somatosensory Cortex; Visual Cortex; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; Wheat Germ Agglutinins}, Month = {Jun}, Number = {1}, Pages = {68-89}, pmid = {2454978}, Pst = {ppublish}, Title = {Characterization of transient cortical projections from auditory, somatosensory, and motor cortices to visual areas 17, 18, and 19 in the kitten}, Volume = {272}, Year = {1988}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902720106}} @article{Kennedy:1989, Abstract = {Area 17 in the neonate of numerous species receives projections from cortical areas that do not project to area 17 in the adult. To investigate if this were the case in the developing primate, we have made injections of retrograde tracers in area 17 of newborn monkeys (Macaca irus) and examined the areal distribution of labeled neurons. Neurons projecting to area 17 were found to be restricted to those cortical regions that project to area 17 in the adult. The projection to area 17 in the neonate did appear to be very different in that in the superior temporal sulcus there was a large contingent of labeled neurons in supragranular layers. This constitutes a transient projection because in the adult area 17 projecting neurons in this cortical region originate almost exclusively from infragranular layers. To test if a change in the laminar distribution of area 17 projecting neurons in extrastriate cortex is a general feature of postnatal development, we have computed in neonates and adults the proportion of area 17 afferent neurons in infra- and supragranular layers for each cortical region that projects to area 17. This revealed (i) that in the adult the laminar distribution of area 17 afferents is characteristic for each cortical area and (ii) that this distribution emerges during development from an immature state in which labeled neurons are more numerous in supragranular layers. These results show that there is an extensive remodeling of the neuronal circuitry connecting visual cortical areas during postnatal development in the monkey and that the transient connectivity of primate area 17 is very different from that observed in other mammalian species.}, Author = {Kennedy, H and Bullier, J and Dehay, C}, Date-Added = {2015-09-02 00:36:41 +0000}, Date-Modified = {2015-09-02 00:36:41 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Aging; Animals; Animals, Newborn; Axonal Transport; Cerebral Cortex; Horseradish Peroxidase; Macaca; Neurons; Visual Cortex; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; Wheat Germ Agglutinins}, Month = {Oct}, Number = {20}, Pages = {8093-7}, Pmc = {PMC298221}, pmid = {2479015}, Pst = {ppublish}, Title = {Transient projection from the superior temporal sulcus to area 17 in the newborn macaque monkey}, Volume = {86}, Year = {1989}} @article{Dehay:1989, Abstract = {In several species, the peripheral input from the eyes partly determines the pattern of interconnections between the visual areas of the two cerebral hemispheres through the fibre tract termed the corpus callosum. In the macaque monkey, the neurons projecting through the callosum are largely restricted to area 18 throughout ontogeny, whereas area 17 is characterized by few or no callosal projections. Here, we show that suppressing the peripheral input by prenatal removal of the eyes leads to a marked reduction in the extent of area 17, resulting in a large shift in the position of the histologically identifiable boundary between the two areas. Even so, the boundary continues to separate an area rich with callosal connections (area 18) from one poor in such projections (area 17), indicating there is no effect on the callosal connectivity of area 17. In contrast, in area 18, eye removal results in many more neurons with callosal projections than in normal animals. The results suggest that the factors that determine the parcellation of cortical areas also specify their connectivity.}, Author = {Dehay, C and Horsburgh, G and Berland, M and Killackey, H and Kennedy, H}, Date-Added = {2015-09-02 00:36:34 +0000}, Date-Modified = {2015-09-02 00:36:34 +0000}, Doi = {10.1038/337265a0}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Corpus Callosum; Electron Transport Complex IV; Eye; Macaca fascicularis; Neurons; Ocular Physiological Phenomena; Reference Values; Retina; Visual Cortex; Visual Fields}, Month = {Jan}, Number = {6204}, Pages = {265-7}, pmid = {2536139}, Pst = {ppublish}, Title = {Maturation and connectivity of the visual cortex in monkey is altered by prenatal removal of retinal input}, Volume = {337}, Year = {1989}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/337265a0}} @article{Seabrook:2013, Abstract = {Neurons in layer VI of visual cortex represent one of the largest sources of nonretinal input to the dorsal lateral geniculate nucleus (dLGN) and play a major role in modulating the gain of thalamic signal transmission. However, little is known about how and when these descending projections arrive and make functional connections with dLGN cells. Here we used a transgenic mouse to visualize corticogeniculate projections to examine the timing of cortical innervation in dLGN. Corticogeniculate innervation occurred at postnatal ages and was delayed compared with the arrival of retinal afferents. Cortical fibers began to enter dLGN at postnatal day 3 (P3) to P4, a time when retinogeniculate innervation is complete. However, cortical projections did not fully innervate dLGN until eye opening (P12), well after the time when retinal inputs from the two eyes segregate to form nonoverlapping eye-specific domains. In vitro thalamic slice recordings revealed that newly arriving cortical axons form functional connections with dLGN cells. However, adult-like responses that exhibited paired pulse facilitation did not fully emerge until 2 weeks of age. Finally, surgical or genetic elimination of retinal input greatly accelerated the rate of corticogeniculate innervation, with axons invading between P2 and P3 and fully innervating dLGN by P8 to P10. However, recordings in genetically deafferented mice showed that corticogeniculate synapses continued to mature at the same rate as controls. These studies suggest that retinal and cortical innervation of dLGN is highly coordinated and that input from retina plays an important role in regulating the rate of corticogeniculate innervation.}, Author = {Seabrook, Tania A and El-Danaf, Rana N and Krahe, Thomas E and Fox, Michael A and Guido, William}, Date-Added = {2015-09-02 00:05:58 +0000}, Date-Modified = {2015-09-02 00:05:58 +0000}, Doi = {10.1523/JNEUROSCI.5271-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Age Factors; Analysis of Variance; Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors; Cholera Toxin; Excitatory Postsynaptic Potentials; Eye Enucleation; Gene Expression Regulation, Developmental; Geniculate Bodies; Green Fluorescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myelin Basic Protein; Nerve Tissue Proteins; Retina; Vesicular Glutamate Transport Protein 1; Visual Cortex; Visual Pathways}, Month = {Jun}, Number = {24}, Pages = {10085-97}, Pmc = {PMC3682386}, pmid = {23761904}, Pst = {ppublish}, Title = {Retinal input regulates the timing of corticogeniculate innervation}, Volume = {33}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5271-12.2013}} @article{Yilmaz:2013, Abstract = {Much of brain science is concerned with understanding the neural circuits that underlie specific behaviors. While the mouse has become a favorite experimental subject, the behaviors of this species are still poorly explored. For example, the mouse retina, like that of other mammals, contains ∼20 different circuits that compute distinct features of the visual scene [1, 2]. By comparison, only a handful of innate visual behaviors are known in this species--the pupil reflex [3], phototaxis [4], the optomotor response [5], and the cliff response [6]--two of which are simple reflexes that require little visual processing. We explored the behavior of mice under a visual display that simulates an approaching object, which causes defensive reactions in some other species [7, 8]. We show that mice respond to this stimulus either by initiating escape within a second or by freezing for an extended period. The probability of these defensive behaviors is strongly dependent on the parameters of the visual stimulus. Directed experiments identify candidate retinal circuits underlying the behavior and lead the way into detailed study of these neural pathways. This response is a new addition to the repertoire of innate defensive behaviors in the mouse that allows the detection and avoidance of aerial predators.}, Author = {Yilmaz, Melis and Meister, Markus}, Date-Added = {2015-08-31 20:29:28 +0000}, Date-Modified = {2015-08-31 20:30:36 +0000}, Doi = {10.1016/j.cub.2013.08.015}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {mouse; mice; visual system; behavior; function; Escape Reaction; aversive; Retina; Retinal Ganglion Cells; Visual Cortex; superior colliculus}, Month = {Oct}, Number = {20}, Pages = {2011-5}, Pmc = {PMC3809337}, pmid = {24120636}, Pst = {ppublish}, Title = {Rapid innate defensive responses of mice to looming visual stimuli}, Volume = {23}, Year = {2013}, url = {papers/Yilmaz_CurrBiol2013.pdf}, Bdsk-File-2 = {papers/Yilmaz_CurrBiol2013a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2013.08.015}} @article{Zhao:2014, Abstract = {Neural circuits in the brain often receive inputs from multiple sources, such as the bottom-up input from early processing stages and the top-down input from higher-order areas. Here we study the function of top-down input in the mouse superior colliculus (SC), which receives convergent inputs from the retina and visual cortex. Neurons in the superficial SC display robust responses and speed tuning to looming stimuli that mimic approaching objects. The looming-evoked responses are reduced by almost half when the visual cortex is optogenetically silenced in awake, but not in anesthetized, mice. Silencing the cortex does not change the looming speed tuning of SC neurons, or the response time course, except at the lowest tested speed. Furthermore, the regulation of SC responses by the corticotectal input is organized retinotopically. This effect we revealed may thus provide a potential substrate for the cortex, an evolutionarily new structure, to modulate SC-mediated visual behaviors.}, Author = {Zhao, Xinyu and Liu, Mingna and Cang, Jianhua}, Date-Added = {2015-08-31 20:09:43 +0000}, Date-Modified = {2015-08-31 20:31:03 +0000}, Doi = {10.1016/j.neuron.2014.08.037}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {mouse; mice; visual system; behavior; function; Escape Reaction; aversive; Retina; Retinal Ganglion Cells; Visual Cortex; superior colliculus}, Mesh = {Animals; Evoked Potentials, Visual; Mice; Mice, Inbred C57BL; Mice, Transgenic; Photic Stimulation; Superior Colliculi; Visual Cortex; Visual Pathways; Wakefulness}, Month = {Oct}, Number = {1}, Pages = {202-13}, Pmc = {PMC4184914}, pmid = {25220812}, Pst = {ppublish}, Title = {Visual cortex modulates the magnitude but not the selectivity of looming-evoked responses in the superior colliculus of awake mice}, Volume = {84}, Year = {2014}, url = {papers/Zhao_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.08.037}} @article{Striem-Amit:2015, Abstract = {Is visual input during critical periods of development crucial for the emergence of the fundamental topographical mapping of the visual cortex? And would this structure be retained throughout life-long blindness or would it fade as a result of plastic, use-based reorganization? We used functional connectivity magnetic resonance imaging based on intrinsic blood oxygen level-dependent fluctuations to investigate whether significant traces of topographical mapping of the visual scene in the form of retinotopic organization, could be found in congenitally blind adults. A group of 11 fully and congenitally blind subjects and 18 sighted controls were studied. The blind demonstrated an intact functional connectivity network structural organization of the three main retinotopic mapping axes: eccentricity (centre-periphery), laterality (left-right), and elevation (upper-lower) throughout the retinotopic cortex extending to high-level ventral and dorsal streams, including characteristic eccentricity biases in face- and house-selective areas. Functional connectivity-based topographic organization in the visual cortex was indistinguishable from the normally sighted retinotopic functional connectivity structure as indicated by clustering analysis, and was found even in participants who did not have a typical retinal development in utero (microphthalmics). While the internal structural organization of the visual cortex was strikingly similar, the blind exhibited profound differences in functional connectivity to other (non-visual) brain regions as compared to the sighted, which were specific to portions of V1. Central V1 was more connected to language areas but peripheral V1 to spatial attention and control networks. These findings suggest that current accounts of critical periods and experience-dependent development should be revisited even for primary sensory areas, in that the connectivity basis for visual cortex large-scale topographical organization can develop without any visual experience and be retained through life-long experience-dependent plasticity. Furthermore, retinotopic divisions of labour, such as that between the visual cortex regions normally representing the fovea and periphery, also form the basis for topographically-unique plastic changes in the blind.}, Author = {Striem-Amit, Ella and Ovadia-Caro, Smadar and Caramazza, Alfonso and Margulies, Daniel S and Villringer, Arno and Amedi, Amir}, Date-Added = {2015-08-28 23:53:42 +0000}, Date-Modified = {2015-08-28 23:58:36 +0000}, Doi = {10.1093/brain/awv083}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {blindness; development; plasticity; vision; activity-development; connectivity; functional connectivity; Neocortex; Visual Cortex; extrastriate; topographic map; resting-state fMRI; Grants}, Mesh = {Adult; Blindness; Case-Control Studies; Functional Neuroimaging; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Retina; Visual Cortex; Visual Pathways; Young Adult}, Month = {Jun}, Number = {Pt 6}, Pages = {1679-95}, pmid = {25869851}, Pst = {ppublish}, Title = {Functional connectivity of visual cortex in the blind follows retinotopic organization principles}, Volume = {138}, Year = {2015}, url = {papers/Striem-Amit_Brain2015.pdf}} @article{Balkema:1981, Abstract = {Mice of the mutant strain pearl (pe/pe) differ from the wild strain by a single gene mutation, which leads to a lightening of the coat color. We tested this strain to see if this mutant gene also expressed itself in one or more visual abnormalities. Pearl mice were found to lack totally the optokinetic nystagmus reflex that was present in every normal mouse that we examined. This lack of optokinetic nystagmus was not due to oculomotor defects, since postrotatory nystagmus was normal. As described for other pigmentation mutants, we found that pearl mutants had a reduced ipsilateral projection to the lateral geniculate nucleus, superior colliculus, and visual cortex. We recorded from single cells in the superior colliculus and found response properties and light sensitivities to be normal over the luminance range at which optokinetic nystagmus was tested. However, at very dim backgrounds (scotopic levels), the incremental sensitivities of these cells in pearl mice were about 100 times lower than those of normal mice. This reduction in sensitivity was restricted to scotopic backgrounds and was not due to abnormalities in either the time course of dark adaptation or the receptive field sizes of single cells. In recordings of the electroretinographic response, both the waveforms and the normalized magnitudes of the A and B waves of pearl were indistinguishable from those of normal mice, which seems to indicate that the cause of pearl's sensitivity defect is located central to the main electrical events in the photoreceptors. The normality of many aspects of the visual system of pearl mice contrasts sharply with the complete absence of optokinetic nystagmus, with the reduced ipsilateral projection, and with the reduced dark sensitivity of the cells in the superior colliculus.}, Author = {Balkema, Jr, G W and Pinto, L H and Dr{\"a}ger, U C and Vanable, Jr, J W}, Date-Added = {2015-08-28 21:54:55 +0000}, Date-Modified = {2015-08-28 21:56:53 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {vision; Visual Cortex; superior colliculus; behavior; Motor Activity;}, Mesh = {Animals; Electric Conductivity; Eye Movements; Mice; Mice, Mutant Strains; Mutation; Neurons; Photic Stimulation; Retina; Retinal Degeneration; Superior Colliculi; Visual Cortex; Visual Perception}, Month = {Nov}, Number = {11}, Pages = {1320-9}, pmid = {7310489}, Pst = {ppublish}, Title = {Characterization of abnormalities in the visual system of the mutant mouse pearl}, Volume = {1}, Year = {1981}} @article{Schneider:1969, Author = {Schneider, G E}, Date-Added = {2015-08-28 21:51:31 +0000}, Date-Modified = {2015-08-28 21:53:38 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {vision; visual cortex; superior colliculus; behavior; Motor Activity}, Mesh = {Animals; Cerebral Cortex; Cricetinae; Discrimination (Psychology); Orientation; Tectum Mesencephali; Vision, Ocular; Visual Cortex}, Month = {Feb}, Number = {3870}, Pages = {895-902}, pmid = {5763873}, Pst = {ppublish}, Title = {Two visual systems}, Volume = {163}, Year = {1969}, Bdsk-Url-1 = {http://www.sciencemag.org/content/163/3870/895.citation}} @article{Prusky:2000, Abstract = {We have developed a simple computer-based discrimination task that enables the quick determination of visual acuities in rodents. A grating is displayed randomly on one of two monitors at the wide end of a trapezoidal-shaped tank containing shallow water. Animals are trained to swim toward the screens, and at a fixed distance, choose the screen displaying the grating and escape to a submerged platform hidden below it. Both mice and rats learn the task quickly. Performance falls below 70% when the spatial frequency is increased beyond 0.5 cycles in most C57BU6 mice, and around 1.0 cycles per degree (cpd) in Long-Evans rats.}, Author = {Prusky, G T and West, P W and Douglas, R M}, Date-Added = {2015-08-28 17:37:22 +0000}, Date-Modified = {2015-08-28 17:38:04 +0000}, Journal = {Vision Res}, Journal-Full = {Vision research}, Keywords = {mouse; mice; vision; behavior; Methods; technique; visual system; Visual Cortex; superior colliculus}, Mesh = {Adaptation, Physiological; Animals; Behavior, Animal; Mice; Mice, Inbred C57BL; Psychophysics; Rats; Rats, Long-Evans; Visual Acuity}, Number = {16}, Pages = {2201-9}, pmid = {10878281}, Pst = {ppublish}, Title = {Behavioral assessment of visual acuity in mice and rats}, Volume = {40}, Year = {2000}, url = {papers/Prusky_VisionRes2000.pdf}} @article{Laramee:2014, Abstract = {In the mouse, visual extrastriate areas are located within distinct acallosal zones. It has been proposed that the striate-extrastriate and callosal projections are interdependent. In visually deprived mice, the normal patterns of callosal and striate-extrastriate projections are disrupted. It remains unknown whether visual deprivation affects the topography of V1-extrastriate projections and their relationship with callosal projections. Two anterograde tracers were injected in V1 and multiple retrograde tracer injections were performed in the contralateral hemisphere of intact and enucleated C57BL/6 mice and in ZRDCT/An mice to determine the effects of prenatal and postnatal afferent sensory activity on the topography of V1-extrastriate and callosal projections. Greater topographic anomalies were found in striate-extrastriate projections of anophthalmic than enucleated mice. In enucleated mice, the relationship between striate-extrastriate projections and callosal zones was highly variable. In anophthalmic mice, there was also a greater overlap between these projections. These results suggest that the prenatal afferent sensory activity regulates some aspects of the distribution of V1-extrastriate and callosal projections, in addition to the development of a normal topographic representation in extrastriate areas.}, Author = {Laram{\'e}e, Marie-Eve and Bronchti, Gilles and Boire, Denis}, Date-Added = {2015-08-27 16:30:30 +0000}, Date-Modified = {2017-05-05 18:43:55 +0000}, Doi = {10.1007/s00429-013-0623-6}, Journal = {Brain Struct Funct}, Journal-Full = {Brain structure \& function}, Keywords = {activity manipulation; activity-dependent; Activity-development; Sensory Deprivation; spontaneous activity; retinal waves; cortical circuits; connectivity; hemisphere; symmetry; extrastriate; Neocortex; Cerebral Cortex; Visual Cortex; mice; mouse; eye; currOpinRvw}, Mesh = {Animals; Anophthalmos; Corpus Callosum; Eye Enucleation; Mice; Mice, Inbred C57BL; Visual Cortex; Visual Pathways}, Month = {Nov}, Number = {6}, Pages = {2051-70}, pmid = {23942645}, Pst = {ppublish}, Title = {Primary visual cortex projections to extrastriate cortices in enucleated and anophthalmic mice}, Volume = {219}, Year = {2014}, url = {papers/Laramée_BrainStructFunct2014.pdf}} @article{Craddock:2013, Abstract = {At macroscopic scales, the human connectome comprises anatomically distinct brain areas, the structural pathways connecting them and their functional interactions. Annotation of phenotypic associations with variation in the connectome and cataloging of neurophenotypes promise to transform our understanding of the human brain. In this Review, we provide a survey of magnetic resonance imaging--based measurements of functional and structural connectivity. We highlight emerging areas of development and inquiry and emphasize the importance of integrating structural and functional perspectives on brain architecture.}, Author = {Craddock, R Cameron and Jbabdi, Saad and Yan, Chao-Gan and Vogelstein, Joshua T and Castellanos, F Xavier and Di Martino, Adriana and Kelly, Clare and Heberlein, Keith and Colcombe, Stan and Milham, Michael P}, Date-Added = {2015-06-22 22:25:31 +0000}, Date-Modified = {2015-06-22 22:25:31 +0000}, Doi = {10.1038/nmeth.2482}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Mesh = {Brain; Connectome; Humans; Magnetic Resonance Imaging; Phenotype}, Month = {Jun}, Number = {6}, Pages = {524-39}, Pmc = {PMC4096321}, pmid = {23722212}, Pst = {ppublish}, Title = {Imaging human connectomes at the macroscale}, Volume = {10}, Year = {2013}, url = {papers/Craddock_NatMethods2013.pdf}} @article{Madisen:2015, Abstract = {UNLABELLED: An increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity. VIDEO ABSTRACT: }, Author = {Madisen, Linda and Garner, Aleena R and Shimaoka, Daisuke and Chuong, Amy S and Klapoetke, Nathan C and Li, Lu and van der Bourg, Alexander and Niino, Yusuke and Egolf, Ladan and Monetti, Claudio and Gu, Hong and Mills, Maya and Cheng, Adrian and Tasic, Bosiljka and Nguyen, Thuc Nghi and Sunkin, Susan M and Benucci, Andrea and Nagy, Andras and Miyawaki, Atsushi and Helmchen, Fritjof and Empson, Ruth M and Kn{\"o}pfel, Thomas and Boyden, Edward S and Reid, R Clay and Carandini, Matteo and Zeng, Hongkui}, Date-Added = {2015-06-22 19:24:49 +0000}, Date-Modified = {2015-06-22 19:24:49 +0000}, Doi = {10.1016/j.neuron.2015.02.022}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Gene Targeting; Hippocampus; Integrases; Mice; Mice, Transgenic; Neurons; Optogenetics; Organ Culture Techniques; Visual Cortex}, Month = {Mar}, Number = {5}, Pages = {942-58}, Pmc = {PMC4365051}, pmid = {25741722}, Pst = {ppublish}, Title = {Transgenic mice for intersectional targeting of neural sensors and effectors with high specificity and performance}, Volume = {85}, Year = {2015}, url = {papers/Madisen_Neuron2015.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2015.02.022}} @article{Daw:2007a, Abstract = {Feedforward inhibitory GABAergic transmission is critical for mature cortical circuit function; in the neonate, however, GABA is depolarizing and believed to have a different role. Here we show that the GABAA receptor-mediated conductance is depolarizing in excitatory (stellate) cells in neonatal (postnatal day [P]3-5) layer IV barrel cortex, but GABAergic transmission at this age is not engaged by thalamocortical input in the feedforward circuit and has no detectable circuit function. However, recruitment occurs at P6-7 as a result of coordinated increases in thalamic drive to fast-spiking interneurons, fast-spiking interneuron-stellate cell connectivity and hyperpolarization of the GABAA receptor-mediated response. Thus, GABAergic circuits are not engaged by thalamocortical input in the neonate, but are poised for a remarkably coordinated development of feedforward inhibition at the end of the first postnatal week, which has profound effects on circuit function at this critical time in development.}, Author = {Daw, Michael I and Ashby, Michael C and Isaac, John T R}, Date-Added = {2015-04-08 23:02:15 +0000}, Date-Modified = {2015-04-08 23:03:28 +0000}, Doi = {10.1038/nn1866}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {plasticity; development; barrels; Somatosensory Cortex; interneurons; GABA;}, Mesh = {Action Potentials; Age Factors; Animals; Animals, Newborn; Bicuculline; Cerebral Cortex; Dose-Response Relationship, Radiation; Electric Stimulation; Excitatory Postsynaptic Potentials; GABA Antagonists; Green Fluorescent Proteins; In Vitro Techniques; Interneurons; Mice; Mice, Transgenic; Neural Pathways; Patch-Clamp Techniques; Thalamus}, Month = {Apr}, Number = {4}, Pages = {453-61}, pmid = {17351636}, Pst = {ppublish}, Title = {Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex}, Volume = {10}, Year = {2007}, url = {papers/Daw_NatNeurosci2007a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1866}} @article{Cruz-Martin:2010, Abstract = {Fragile X syndrome (FXS) causes mental impairment and autism through transcriptional silencing of the Fmr1 gene, resulting in the loss of the RNA-binding protein fragile X mental retardation protein (FMRP). Cortical pyramidal neurons in affected individuals and Fmr1 knock-out (KO) mice have an increased density of dendritic spines. The mutant mice also show defects in synaptic and experience-dependent circuit plasticity, which are known to be mediated in part by dendritic spine dynamics. We used in vivo time-lapse imaging with two-photon microscopy through cranial windows in male and female neonatal mice to test the hypothesis that dynamics of dendritic protrusions are altered in KO mice during early postnatal development. We find that layer 2/3 neurons from wild-type mice exhibit a rapid decrease in dendritic spine dynamics during the first 2 postnatal weeks, as immature filopodia are replaced by mushroom spines. In contrast, KO mice show a developmental delay in the downregulation of spine turnover and in the transition from immature to mature spine subtypes. Blockade of metabotropic glutamate receptor (mGluR) signaling, which reverses some adult phenotypes of KO mice, accentuated this immature protrusion phenotype in KO mice. Thus, absence of FMRP delays spine stabilization and dysregulated mGluR signaling in FXS may partially normalize this early synaptic defect.}, Author = {Cruz-Mart{\'\i}n, Alberto and Crespo, Michelle and Portera-Cailliau, Carlos}, Date-Added = {2015-04-08 22:35:31 +0000}, Date-Modified = {2015-04-08 22:55:49 +0000}, Doi = {10.1523/JNEUROSCI.0577-10.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {plasticity; Structure-Activity Relationship; structural remodeling; autism; Autistic Disorder; Grants; mouse; in vivo; two-photon imaging; spines; synapse formation; Somatosensory Cortex; Neocortex; development}, Mesh = {Animals; Animals, Newborn; Dendritic Spines; Disease Models, Animal; Excitatory Amino Acid Antagonists; Fragile X Mental Retardation Protein; Fragile X Syndrome; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Pseudopodia; Pyridines; Receptors, Metabotropic Glutamate}, Month = {Jun}, Number = {23}, Pages = {7793-803}, Pmc = {PMC2903441}, pmid = {20534828}, Pst = {ppublish}, Title = {Delayed stabilization of dendritic spines in fragile X mice}, Volume = {30}, Year = {2010}, url = {papers/Cruz-Martín_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0577-10.2010}} @article{Zuo:2005a, Abstract = {Synapse formation and elimination occur throughout life, but the magnitude of such changes at distinct developmental stages remains unclear. Using transgenic mice overexpressing yellow fluorescent protein and transcranial two-photon microscopy, we repeatedly imaged dendritic spines on the apical dendrites of layer 5 pyramidal neurons. In young adolescent mice (1-month-old), 13%-20% of spines were eliminated and 5%-8% formed over 2 weeks in barrel, motor, and frontal cortices, indicating a cortical-wide spine loss during this developmental period. As animals mature, there is also a substantial loss of dendritic filopodia involved in spinogenesis. In adult mice (4-6 months old), 3%-5% of spines were eliminated and formed over 2 weeks in various cortical regions. Over 18 months, only 26% of spines were eliminated and 19% formed in adult barrel cortex. Thus, after a concurrent loss of spines and spine precursors in diverse regions of young adolescent cortex, spines become stable and a majority of them can last throughout life.}, Author = {Zuo, Yi and Lin, Aerie and Chang, Paul and Gan, Wen-Biao}, Date-Added = {2015-04-08 22:28:15 +0000}, Date-Modified = {2015-04-08 22:29:02 +0000}, Doi = {10.1016/j.neuron.2005.04.001}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {plasticity; Neocortex; Somatosensory Cortex; barrels; structural remodeling; Structure-Activity Relationship; spines; in vivo; two-photon imaging}, Mesh = {Aging; Animals; Cerebral Cortex; Dendritic Spines; Green Fluorescent Proteins; Imaging, Three-Dimensional; Mice; Mice, Transgenic}, Month = {Apr}, Number = {2}, Pages = {181-9}, pmid = {15848798}, Pst = {ppublish}, Title = {Development of long-term dendritic spine stability in diverse regions of cerebral cortex}, Volume = {46}, Year = {2005}, url = {papers/Zuo_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.001}} @article{Carvell:1996, Abstract = {The importance of early tactile experience in the development of discriminative somatomotor function was assessed by examining the proficiency and movement strategies of rats raised without normal sensory inputs provided by their mystacial vibrissae. Infant-trimmed animals had their whiskers clipped daily from birth to 45 d of age, after which they were allowed to regrow for 60-70 d before initiation of behavioral training, which lasted as long as several months. Adult-trimmed animals had their whiskers trimmed for comparable periods during adulthood. Rats were tested on one of two tactile discriminations, rough versus smooth or rough versus rough, that differed with respect to the overall size of their surface features. Whisker movements during task performance were examined in detail using video-based motion analysis software. Infant-trimmed animals performed rough versus smooth discriminations as well as adult-trimmed rats or normally reared animals. Except for one subject, infant-trimmed rats were severely impaired in their ability to distinguish rough versus rough surfaces. Deficits persisted in spite of months of training with the regrown vibrissae. The animals that failed to master this task displayed whisking patterns that notably lacked frequencies in the normal range of 6-12 Hz. Thus, abnormal tactile experience early in life substantially, and perhaps permanently, impairs sensorimotor integration underlying active touch.}, Author = {Carvell, G E and Simons, D J}, Date-Added = {2015-04-08 22:25:18 +0000}, Date-Modified = {2015-04-08 22:25:43 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {plasticity; Sensory Deprivation; structural remodeling; Structure-Activity Relationship; Somatosensory Cortex; Neocortex; sensory map; topographic map}, Mesh = {Animals; Animals, Newborn; Behavior, Animal; Discrimination (Psychology); Female; Pregnancy; Rats; Rats, Sprague-Dawley; Sensory Deprivation; Somatosensory Cortex; Time Factors; Touch}, Month = {Apr}, Number = {8}, Pages = {2750-7}, pmid = {8786450}, Pst = {ppublish}, Title = {Abnormal tactile experience early in life disrupts active touch}, Volume = {16}, Year = {1996}, url = {papers/Carvell_JNeurosci1996.pdf}} @article{Hofer:2009, Abstract = {Sensory experiences exert a powerful influence on the function and future performance of neuronal circuits in the mammalian neocortex. Restructuring of synaptic connections is believed to be one mechanism by which cortical circuits store information about the sensory world. Excitatory synaptic structures, such as dendritic spines, are dynamic entities that remain sensitive to alteration of sensory input throughout life. It remains unclear, however, whether structural changes at the level of dendritic spines can outlast the original experience and thereby provide a morphological basis for long-term information storage. Here we follow spine dynamics on apical dendrites of pyramidal neurons in functionally defined regions of adult mouse visual cortex during plasticity of eye-specific responses induced by repeated closure of one eye (monocular deprivation). The first monocular deprivation episode doubled the rate of spine formation, thereby increasing spine density. This effect was specific to layer-5 cells located in binocular cortex, where most neurons increase their responsiveness to the non-deprived eye. Restoring binocular vision returned spine dynamics to baseline levels, but absolute spine density remained elevated and many monocular deprivation-induced spines persisted during this period of functional recovery. However, spine addition did not increase again when the same eye was closed for a second time. This absence of structural plasticity stands out against the robust changes of eye-specific responses that occur even faster after repeated deprivation. Thus, spines added during the first monocular deprivation experience may provide a structural basis for subsequent functional shifts. These results provide a strong link between functional plasticity and specific synaptic rearrangements, revealing a mechanism of how prior experiences could be stored in cortical circuits.}, Author = {Hofer, Sonja B and Mrsic-Flogel, Thomas D and Bonhoeffer, Tobias and H{\"u}bener, Mark}, Date-Added = {2015-04-08 22:18:30 +0000}, Date-Modified = {2015-04-08 22:20:25 +0000}, Doi = {10.1038/nature07487}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {plasticity; Sensory Deprivation; structural remodeling; Structure-Activity Relationship; Visual Cortex; Neocortex; sensory map; topographic map}, Mesh = {Animals; Dendrites; Mice; Mice, Inbred C57BL; Models, Neurological; Neural Pathways; Neuronal Plasticity; Pyramidal Cells; Vision, Binocular; Vision, Monocular; Visual Cortex}, Month = {Jan}, Number = {7227}, Pages = {313-7}, pmid = {19005470}, Pst = {ppublish}, Title = {Experience leaves a lasting structural trace in cortical circuits}, Volume = {457}, Year = {2009}, url = {papers/Hofer_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07487}} @article{Hofer:2010, Abstract = {Recent advances in multi-electrode recording and imaging techniques have made it possible to observe the activity of large populations of neurons. However, to take full advantage of these techniques, new methods for the analysis of population responses must be developed. In this paper, we present an algorithm for optimizing population decoding with distance metrics. To demonstrate the utility of this algorithm under experimental conditions, we evaluate its performance in decoding both population spike trains and calcium signals with different correlation structures. Our results demonstrate that the optimized decoder outperforms other simple population decoders and suggest that optimization could serve as a tool for quantifying the potential contribution of individual cells to the population code.}, Author = {Hofer, Sonja B and Mrsic-Flogel, Thomas D and Horvath, Domonkos and Grothe, Benedikt and Lesica, Nicholas A}, Date-Added = {2015-02-25 16:28:01 +0000}, Date-Modified = {2015-02-25 16:28:01 +0000}, Doi = {10.1016/j.neunet.2010.04.007}, Journal = {Neural Netw}, Journal-Full = {Neural networks : the official journal of the International Neural Network Society}, Mesh = {Action Potentials; Algorithms; Animals; Computer Simulation; Electrophysiology; Gerbillinae; Nerve Net; Neural Networks (Computer); Neurons; Neurophysiology; Signal Processing, Computer-Assisted}, Month = {Aug}, Number = {6}, Pages = {728-32}, pmid = {20488662}, Pst = {ppublish}, Title = {Optimization of population decoding with distance metrics}, Volume = {23}, Year = {2010}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neunet.2010.04.007}} @article{Mrsic-Flogel:2012, Author = {Mrsic-Flogel, Thomas D and Bonhoeffer, Tobias}, Date-Added = {2015-02-25 16:27:47 +0000}, Date-Modified = {2015-02-25 16:27:47 +0000}, Doi = {10.1038/486041a}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Cell Communication; Cell Lineage; Electric Conductivity; Electrical Synapses; Female; Gap Junctions; Male; Neocortex; Neurons; Visual Cortex}, Month = {Jun}, Number = {7401}, Pages = {41-2}, pmid = {22678277}, Pst = {epublish}, Title = {Neuroscience: Sibling neurons bond to share sensations}, Volume = {486}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/486041a}} @article{Han:2013, Author = {Han, Yunyun and Mrsic-Flogel, Thomas}, Date-Added = {2015-02-25 16:27:40 +0000}, Date-Modified = {2015-02-25 16:27:40 +0000}, Doi = {10.1038/nn.3507}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Afferent Pathways; Animals; Auditory Cortex; Cerebral Cortex; Female; Linear Models; Male; Nerve Net; Neurons; Orientation; Sensory Receptor Cells; Thalamus; Visual Cortex; Visual Fields; Visual Pathways}, Month = {Sep}, Number = {9}, Pages = {1166-8}, pmid = {23982448}, Pst = {ppublish}, Title = {A finely tuned cortical amplifier}, Volume = {16}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.3507}} @article{Pecka:2014, Abstract = {At eye opening, neurons in primary visual cortex (V1) are selective for stimulus features, but circuits continue to refine in an experience-dependent manner for some weeks thereafter. How these changes contribute to the coding of visual features embedded in complex natural scenes remains unknown. Here we show that normal visual experience after eye opening is required for V1 neurons to develop a sensitivity for the statistical structure of natural stimuli extending beyond the boundaries of their receptive fields (RFs), which leads to improvements in coding efficiency for full-field natural scenes (increased selectivity and information rate). These improvements are mediated by an experience-dependent increase in the effectiveness of natural surround stimuli to hyperpolarize the membrane potential specifically during RF-stimulus epochs triggering action potentials. We suggest that neural circuits underlying surround modulation are shaped by the statistical structure of visual input, which leads to more selective coding of features in natural scenes.}, Author = {Pecka, Michael and Han, Yunyun and Sader, Elie and Mrsic-Flogel, Thomas D}, Date-Added = {2015-02-25 16:27:32 +0000}, Date-Modified = {2015-02-25 16:29:37 +0000}, Doi = {10.1016/j.neuron.2014.09.010}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {visual system; Visual Cortex; sensory coding; excitatory; Patch-Clamp Techniques; Mouse; in vivo; sensory map;}, Mesh = {Action Potentials; Animals; Animals, Newborn; Mice, Inbred C57BL; Models, Neurological; Nervous System; Neurons; Photic Stimulation; Visual Cortex; Visual Fields; Visual Pathways; Visual Perception}, Month = {Oct}, Number = {2}, Pages = {457-69}, Pmc = {PMC4210638}, pmid = {25263755}, Pst = {ppublish}, Title = {Experience-dependent specialization of receptive field surround for selective coding of natural scenes}, Volume = {84}, Year = {2014}, url = {papers/Pecka_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.09.010}} @article{Cossell:2015, Abstract = {The strength of synaptic connections fundamentally determines how neurons influence each other's firing. Excitatory connection amplitudes between pairs of cortical neurons vary over two orders of magnitude, comprising only very few strong connections among many weaker ones. Although this highly skewed distribution of connection strengths is observed in diverse cortical areas, its functional significance remains unknown: it is not clear how connection strength relates to neuronal response properties, nor how strong and weak inputs contribute to information processing in local microcircuits. Here we reveal that the strength of connections between layer 2/3 (L2/3) pyramidal neurons in mouse primary visual cortex (V1) obeys a simple rule--the few strong connections occur between neurons with most correlated responses, while only weak connections link neurons with uncorrelated responses. Moreover, we show that strong and reciprocal connections occur between cells with similar spatial receptive field structure. Although weak connections far outnumber strong connections, each neuron receives the majority of its local excitation from a small number of strong inputs provided by the few neurons with similar responses to visual features. By dominating recurrent excitation, these infrequent yet powerful inputs disproportionately contribute to feature preference and selectivity. Therefore, our results show that the apparently complex organization of excitatory connection strength reflects the similarity of neuronal responses, and suggest that rare, strong connections mediate stimulus-specific response amplification in cortical microcircuits.}, Author = {Cossell, Lee and Iacaruso, Maria Florencia and Muir, Dylan R and Houlton, Rachael and Sader, Elie N and Ko, Ho and Hofer, Sonja B and Mrsic-Flogel, Thomas D}, Date-Added = {2015-02-25 16:25:50 +0000}, Date-Modified = {2015-02-25 16:26:48 +0000}, Doi = {10.1038/nature14182}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {visual system; Visual Cortex; functional connectivity; excitatory; Patch-Clamp Techniques; optical imaging; calcium imaging; Mouse; in vivo; sensory map;}, Month = {Feb}, Number = {7539}, Pages = {399-403}, pmid = {25652823}, Pst = {ppublish}, Title = {Functional organization of excitatory synaptic strength in primary visual cortex}, Volume = {518}, Year = {2015}, url = {papers/Cossell_Nature2015.pdf}} @article{Harris:2013a, Abstract = {The sensory cortex contains a wide array of neuronal types, which are connected together into complex but partially stereotyped circuits. Sensory stimuli trigger cascades of electrical activity through these circuits, causing specific features of sensory scenes to be encoded in the firing patterns of cortical populations. Recent research is beginning to reveal how the connectivity of individual neurons relates to the sensory features they encode, how differences in the connectivity patterns of different cortical cell classes enable them to encode information using different strategies, and how feedback connections from higher-order cortex allow sensory information to be integrated with behavioural context.}, Author = {Harris, Kenneth D and Mrsic-Flogel, Thomas D}, Date-Added = {2015-02-25 16:05:04 +0000}, Date-Modified = {2015-02-25 16:06:01 +0000}, Doi = {10.1038/nature12654}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {review literature; behavior; sensory map; connectivity; neuron;; Visual Cortex; visual system}, Mesh = {Animals; Auditory Cortex; Cerebral Cortex; Interneurons; Models, Neurological; Neural Pathways; Sensory Receptor Cells; Somatosensory Cortex; Visual Cortex}, Month = {Nov}, Number = {7474}, Pages = {51-8}, pmid = {24201278}, Pst = {ppublish}, Title = {Cortical connectivity and sensory coding}, Volume = {503}, Year = {2013}, url = {papers/Harris_Nature2013.pdf}} @article{Mitra:1999, Abstract = {Modern imaging techniques for probing brain function, including functional magnetic resonance imaging, intrinsic and extrinsic contrast optical imaging, and magnetoencephalography, generate large data sets with complex content. In this paper we develop appropriate techniques for analysis and visualization of such imaging data to separate the signal from the noise and characterize the signal. The techniques developed fall into the general category of multivariate time series analysis, and in particular we extensively use the multitaper framework of spectral analysis. We develop specific protocols for the analysis of fMRI, optical imaging, and MEG data, and illustrate the techniques by applications to real data sets generated by these imaging modalities. In general, the analysis protocols involve two distinct stages: "noise" characterization and suppression, and "signal" characterization and visualization. An important general conclusion of our study is the utility of a frequency-based representation, with short, moving analysis windows to account for nonstationarity in the data. Of particular note are 1) the development of a decomposition technique (space-frequency singular value decomposition) that is shown to be a useful means of characterizing the image data, and 2) the development of an algorithm, based on multitaper methods, for the removal of approximately periodic physiological artifacts arising from cardiac and respiratory sources.}, Author = {Mitra, P P and Pesaran, B}, Date-Added = {2015-01-27 09:52:05 +0000}, Date-Modified = {2015-01-27 11:22:12 +0000}, Doi = {10.1016/S0006-3495(99)77236-X}, Journal = {Biophys J}, Journal-Full = {Biophysical journal}, Keywords = {Brain; Fourier Analysis; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetoencephalography; Multivariate Analysis; Computational Biology; optical imaging; neurophysiology; Mathematics; technique}, Mesh = {Brain; Fourier Analysis; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetoencephalography; Multivariate Analysis}, Month = {Feb}, Number = {2}, Pages = {691-708}, Pmc = {PMC1300074}, pmid = {9929474}, Pst = {ppublish}, Title = {Analysis of dynamic brain imaging data}, Volume = {76}, Year = {1999}, url = {papers/Mitra_BiophysJ1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0006-3495(99)77236-X}} @article{Sengupta:1999, Abstract = {The singular value decomposition is a matrix decomposition technique widely used in the analysis of multivariate data, such as complex space-time images obtained in both physical and biological systems. In this paper, we examine the distribution of singular values of low-rank matrices corrupted by additive noise. Past studies have been limited to uniform uncorrelated noise. Using diagrammatic and saddle point integration techniques, we extend these results to heterogeneous and correlated noise sources. We also provide perturbative estimates of error bars on the reconstructed low-rank matrix obtained by truncating a singular value decomposition.}, Author = {Sengupta, A M and Mitra, P P}, Date-Added = {2015-01-27 08:00:32 +0000}, Date-Modified = {2015-01-27 08:00:32 +0000}, Journal = {Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics}, Journal-Full = {Physical review. E, Statistical physics, plasmas, fluids, and related interdisciplinary topics}, Month = {Sep}, Number = {3}, Pages = {3389-92}, pmid = {11970154}, Pst = {ppublish}, Title = {Distributions of singular values for some random matrices}, Volume = {60}, Year = {1999}, url = {papers/Sengupta_PhysRevEStatPhysPlasmasFluidsRelatInterdiscipTopics1999.pdf}} @article{Ben-Ari:2012a, Author = {Ben-Ari, Yehezkel}, Date-Added = {2015-01-13 15:47:39 +0000}, Date-Modified = {2015-01-13 15:47:39 +0000}, Doi = {10.3389/fncel.2012.00045}, Journal = {Front Cell Neurosci}, Journal-Full = {Frontiers in cellular neuroscience}, Pages = {45}, Pmc = {PMC3494101}, pmid = {23162428}, Pst = {epublish}, Title = {The Yin and Yen of GABA in Brain Development and Operation in Health and Disease}, Volume = {6}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncel.2012.00045}} @article{Ben-Ari:2012, Abstract = {DURING BRAIN DEVELOPMENT, THERE IS A PROGRESSIVE REDUCTION OF INTRACELLULAR CHLORIDE ASSOCIATED WITH A SHIFT IN GABA POLARITY: GABA depolarizes and occasionally excites immature neurons, subsequently hyperpolarizing them at later stages of development. This sequence, which has been observed in a wide range of animal species, brain structures and preparations, is thought to play an important role in activity-dependent formation and modulation of functional circuits. This sequence has also been considerably reinforced recently with new data pointing to an evolutionary preserved rule. In a recent "Hypothesis and Theory Article," the excitatory action of GABA in early brain development is suggested to be "an experimental artefact" (Bregestovski and Bernard, 2012). The authors suggest that the excitatory action of GABA is due to an inadequate/insufficient energy supply in glucose-perfused slices and/or to the damage produced by the slicing procedure. However, these observations have been repeatedly contradicted by many groups and are inconsistent with a large body of evidence including the fact that the developmental shift is neither restricted to slices nor to rodents. We summarize the overwhelming evidence in support of both excitatory GABA during development, and the implications this has in developmental neurobiology.}, Author = {Ben-Ari, Yehezkel and Woodin, Melanie A and Sernagor, Evelyne and Cancedda, Laura and Vinay, Laurent and Rivera, Claudio and Legendre, Pascal and Luhmann, Heiko J and Bordey, Angelique and Wenner, Peter and Fukuda, Atsuo and van den Pol, Anthony N and Gaiarsa, Jean-Luc and Cherubini, Enrico}, Date-Added = {2015-01-13 15:47:36 +0000}, Date-Modified = {2015-01-13 15:47:36 +0000}, Doi = {10.3389/fncel.2012.00035}, Journal = {Front Cell Neurosci}, Journal-Full = {Frontiers in cellular neuroscience}, Keywords = {GABA; brain slices; chloride homeostasis; development; energy substrates; giant depolarizing potentials}, Pages = {35}, Pmc = {PMC3428604}, pmid = {22973192}, Pst = {epublish}, Title = {Refuting the challenges of the developmental shift of polarity of GABA actions: GABA more exciting than ever!}, Volume = {6}, Year = {2012}, url = {papers/Ben-Ari_FrontCellNeurosci2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncel.2012.00035}} @article{Deidda:2015, Abstract = {Hyperpolarizing and inhibitory GABA regulates critical periods for plasticity in sensory cortices. Here we examine the role of early, depolarizing GABA in the control of plasticity mechanisms. We report that brief interference with depolarizing GABA during early development prolonged critical-period plasticity in visual cortical circuits without affecting the overall development of the visual system. The effects on plasticity were accompanied by dampened inhibitory neurotransmission, downregulation of brain-derived neurotrophic factor (BDNF) expression and reduced density of extracellular matrix perineuronal nets. Early interference with depolarizing GABA decreased perinatal BDNF signaling, and a pharmacological increase of BDNF signaling during GABA interference rescued the effects on plasticity and its regulators later in life. We conclude that depolarizing GABA exerts a long-lasting, selective modulation of plasticity of cortical circuits by a strong crosstalk with BDNF.}, Author = {Deidda, Gabriele and Allegra, Manuela and Cerri, Chiara and Naskar, Shovan and Bony, Guillaume and Zunino, Giulia and Bozzi, Yuri and Caleo, Matteo and Cancedda, Laura}, Date-Added = {2015-01-13 15:44:16 +0000}, Date-Modified = {2015-01-13 15:44:16 +0000}, Doi = {10.1038/nn.3890}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Month = {Jan}, Number = {1}, Pages = {87-96}, pmid = {25485756}, Pst = {ppublish}, Title = {Early depolarizing GABA controls critical-period plasticity in the rat visual cortex}, Volume = {18}, Year = {2015}, url = {papers/Deidda_NatNeurosci2015.pdf}} @article{Liegeois:2010, Abstract = {Hemispherectomy (disconnection or removal of an entire cerebral hemisphere) is a rare surgical procedure used for the relief of drug-resistant epilepsy in children. After hemispherectomy, contralateral hemiplegia persists whereas gross expressive and receptive language functions can be remarkably spared. Motor speech deficits have rarely been examined systematically, thus limiting the accuracy of postoperative prognosis. We describe the speech profiles of hemispherectomized participants characterizing their intelligibility, articulation, phonological speech errors, dysarthric features, and execution and sequencing of orofacial speech and non-speech movements. Thirteen participants who had undergone hemispherectomy (six left, seven right; nine with congenital, four with acquired hemiplegia; operated between four months and 13 years) were investigated. Results showed that all participants were intelligible but showed a mild dysarthric profile characterized by neuromuscular asymmetry and reduced quality and coordination of movements, features that are characteristic of adult-onset unilateral upper motor neuron dysarthria, flaccid-ataxic variant. In addition, one left and four right hemispherectomy cases presented with impaired production of speech and non-speech sequences. No participant showed evidence of verbal or oral dyspraxia. It is concluded that mild dysarthria is persistent after left or right hemispherectomy, irrespective of age at onset of hemiplegia. These results indicate incomplete functional re-organization for the control of fine speech motor movements throughout childhood, and provide no evidence of hemispheric differences.}, Author = {Li{\'e}geois, Fr{\'e}d{\'e}rique and Morgan, Angela T and Stewart, Lorna H and Helen Cross, J and Vogel, Adam P and Vargha-Khadem, Faraneh}, Date-Added = {2014-12-12 20:31:05 +0000}, Date-Modified = {2014-12-12 20:31:14 +0000}, Doi = {10.1016/j.bandl.2009.12.004}, Journal = {Brain Lang}, Journal-Full = {Brain and language}, Keywords = {HEMIPLEGIA; NEUROSURGERY; SPEECH; hemipshere; hemispherectomy; cerebral; cortex; cortical; human}, Mesh = {Adolescent; Child; Child, Preschool; Dysarthria; Epilepsy; Female; Hemiplegia; Hemispherectomy; Humans; Infant; Language Development; Male; Neuronal Plasticity; Postoperative Complications; Recovery of Function; Speech; Speech Articulation Tests; Speech Intelligibility; Speech Perception; Young Adult}, Month = {Aug}, Number = {2}, Pages = {126-34}, pmid = {20096448}, Pst = {ppublish}, Title = {Speech and oral motor profile after childhood hemispherectomy}, Volume = {114}, Year = {2010}, url = {papers/Liégeois_BrainLang2010.pdf}} @article{Basser:1962, Author = {Basser, L S}, Date-Added = {2014-12-12 20:09:58 +0000}, Date-Modified = {2016-01-13 18:16:44 +0000}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {HEMIPLEGIA; NEUROSURGERY; SPEECH; hemipshere; hemispherectomy; cerebral; cortex; cortical; human}, Mesh = {Hemiplegia; Neurosurgery; Speech}, Month = {Sep}, Pages = {427-60}, pmid = {13969875}, Pst = {ppublish}, Title = {Hemiplegia of early onset and the faculty of speech with special reference to the effects of hemispherectomy}, Volume = {85}, Year = {1962}, url = {papers/BASSER_Brain1962.pdf}} @article{Ackman2014c, Abstract = {The cerebral cortex exhibits spontaneous and sensory evoked patterns of activity during early development that is vital for the formation and refinement of neural circuits. Identifying the source and flow of this activity locally and globally is critical for understanding principles guiding self-organization in the developing brain. Here we use whole brain transcranial optical imaging at high spatial and temporal resolution to demonstrate that dynamical patterns of neuronal activity in developing mouse neocortex consist of spatially discrete domains that are coordinated in an age, areal, and behavior- dependent fashion. Ongoing cortical activity displays mirror-symmetric activation patterns across the cerebral hemispheres and stereotyped network architectures that are shaped during development, with parietal-sensorimotor subnetworks functionally connected to occipital regions through frontal-medial cortical areas. This study provides the first broad description of population activity in the developing neocortex at a scope and scale that bridges the microscopic and macroscopic spatiotemporal resolutions provided by traditional neurophysiological and functional neuroimaging techniques. Mesoscale maps of cortical population dynamics within animal models will be crucial for future efforts to understand and treat neurodevelopmental disorders.}, Author = {Ackman, James B and Zeng, Hongkui and Crair, Michael C}, Date-Added = {2014-12-10 16:14:44 +0000}, Date-Modified = {2017-12-01 02:11:23 +0000}, Doi = {10.1101/012237}, Journal = {bioRxiv}, publisher = {Cold Spring Harbor Laboratory}, Month = {Dec}, Title = {Structured dynamics of neural activity across developing neocortex}, Year = {2014}, url = {papers/Ackman_bioRxiv2014.pdf}, eprint = {http://dx.doi.org/10.1101/012237}, eprint = {https://www.biorxiv.org/content/early/2014/12/05/012237.full.pdf}} @article{Mullen2021, author = {Mullen, Brian R. and Weiser, Sydney C. and Ascencio, Desiderio and Ackman, James B.}, title = {Automated classification of signal sources in mesoscale calcium imaging}, elocation-id = {2021.02.23.432573}, year = {2021}, doi = {10.1101/2021.02.23.432573}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Functional imaging of neural cell populations is critical for mapping intra- and inter-regional network dynamics across the neocortex. Recently we showed that an unsupervised machine learning decomposition of densely sampled recordings of cortical calcium dynamics results in a collection of components comprised of neuronal signal sources distinct from optical, movement, and vascular artifacts. Here we build a supervised learning classifier that automatically separates neural activity and artifact components, using a set of extracted spatial and temporal metrics that characterize the respective components. We demonstrate that the performance of the machine classifier matches human identification of signal components in novel data sets. Further, we analyze control data recorded in glial cell reporter and non-fluorescent mouse lines that validates human and machine identification of functional component class. This combined workflow of data-driven video decomposition and machine classification of signal sources will aid robust and scalable mapping of complex cerebral dynamics.Competing Interest StatementThe authors have declared no competing interest.}, eprint = {https://www.biorxiv.org/content/10.1101/2021.02.23.432573v1.full.pdf}, journal = {bioRxiv} } @article{Weiser2020, author = {Weiser, Sydney C. and Mullen, Brian R. and Ascencio, Desiderio and Ackman, James B.}, title = {Data-driven filtration and segmentation of mesoscale neural dynamics}, elocation-id = {2020.12.30.424865}, year = {2021}, doi = {10.1101/2020.12.30.424865}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Recording neuronal group activity across the cortical hemispheres from awake, behaving mice is essential for understanding information flow across cerebral networks. Video recordings of cerebral function comes with challenges, including optical and movement-associated vessel artifacts, and limited references for time series extraction. Here we present a data-driven workflow that isolates artifacts from calcium activity patterns, and segments independent functional units across the cortical surface. Independent Component Analysis utilizes the statistical interdependence of pixel activation to completely unmix signals from background noise, given sufficient spatial and temporal samples. We also utilize isolated signal components to produce segmentations of the cortical surface, unique to each individual{\textquoteright}s functional patterning. Time series extraction from these maps maximally represent the underlying signal in a highly compressed format. These improved techniques for data pre-processing, spatial segmentation, and time series extraction result in optimal signals for further analysis.}, eprint = {https://www.biorxiv.org/content/10.1101/2020.12.30.424865v2.full.pdf}, journal = {bioRxiv}} @article{Sakaki:1997, Abstract = {Depletion of intracellular Ca2+ stores induces a capacitative Ca2+ influx in non-neural cells. It has been unknown whether the capacitative Ca2+ influx occurs in the cells of nervous systems. We found the capacitative Ca2+ influx in the neural retina of early embryonic chick with Fura-2 fluorescence measurements. A Ca(2+)-free medium containing thapsigargin (500 nM), an inhibitor of Ca(2+)-ATPase of intracellular Ca2+ stores, was applied to the neural retina of embryonic day 3 (E3) chick. A rise in intracellular Ca2+ concentration was evoked after the reintroduction of extracellular Ca2+, and this Ca2+ rise was suppressed by Zn2+ (1 mM) and Ni2+ (5 mM). The developmental changes in the Ca2+ rise induced by thapsigargin (250 nM) were studied from E3 to E13. The thapsigargin-induced Ca2+ rise was largest at E3, declined rapidly toward E6, and then decreased gradually until E13, when the Ca2+ rise almost disappeared. This developmental profile correlated with the decline in the mitotic activities of the retinal cells studied by Prada et al. The fluorescence imaging with the vertical slice of the E9 retina showed that the site at which the thapsigargin-induced Ca2+ rise was largest was the most outer layer of the retina, where proliferating cells are located. This spatial distribution and the above developmental profile may suggest that the capacitative Ca2+ influx occurs at the early period of neurogenesis when the cells have mitotic activities.}, Author = {Sakaki, Y and Sugioka, M and Fukuda, Y and Yamashita, M}, Date-Added = {2014-12-09 21:38:47 +0000}, Date-Modified = {2014-12-09 21:38:47 +0000}, Journal = {J Neurobiol}, Journal-Full = {Journal of neurobiology}, Mesh = {Animals; Calcium; Chick Embryo; Electric Conductivity; Enzyme Inhibitors; Fluorescent Dyes; Fura-2; Neurons; Retina; Thapsigargin}, Month = {Jan}, Number = {1}, Pages = {62-8}, pmid = {8989663}, Pst = {ppublish}, Title = {Capacitative Ca2+ influx in the neural retina of chick embryo}, Volume = {32}, Year = {1997}, url = {papers/Sakaki_JNeurobiol1997.pdf}} @article{Rash:2001, Abstract = {In many vertebrate and invertebrate systems, pioneering axons play a crucial role in establishing large axon tracts. Previous studies have addressed whether the first axons to cross the midline to from the corpus callosum arise from neurons in either the cingulate cortex (Koester and O'Leary [1994] J. Neurosci. 11:6608-6620) or the rostrolateral neocortex (Ozaki and Wahlsten [1998] J. Comp. Neurol. 400:197-206). However, these studies have not provided a consensus on which populations pioneer the corpus callosum. We have found that neurons within the cingulate cortex project axons that cross the midline and enter the contralateral hemisphere at E15.5. By using different carbocyanine dyes injected into either the cingulate cortex or the neocortex of the same brain, we found that cingulate axons crossed the midline before neocortical axons and projected into the contralateral cortex. Furthermore, the first neocortical axons to reach the midline crossed within the tract formed by these cingulate callosal axons, and appeared to fasciculate with them as they crossed the midline. These data indicate that axons from the cingulate cortex might pioneer a pathway for later arriving neocortical axons that form the corpus callosum. We also found that a small number of cingulate axons project to the septum as well as to the ipsilateral hippocampus via the fornix. In addition, we found that neurons in the cingulate cortex projected laterally to the rostrolateral neocortex at least 1 day before the neocortical axons reach the midline. Because the rostrolateral neocortex is the first neocortical region to develop, it sends the first neocortical axons to the midline to form the corpus callosum. We postulate that, together, both laterally and medially projecting cingulate axons may pioneer a path for the medially directed neocortical axons, thus helping to guide these axons toward and across the midline during the formation of the corpus callosum.}, Author = {Rash, B G and Richards, L J}, Date-Added = {2014-10-15 19:41:49 +0000}, Date-Modified = {2014-10-15 19:41:49 +0000}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Age Factors; Animals; Carbocyanines; Cell Communication; Cell Differentiation; Corpus Callosum; Efferent Pathways; Female; Fetus; Fluorescent Dyes; Fornix, Brain; Functional Laterality; Growth Cones; Gyrus Cinguli; Hippocampus; Mice; Mice, Inbred C57BL; Neocortex; Pyridinium Compounds; Septal Nuclei}, Month = {May}, Number = {2}, Pages = {147-57}, pmid = {11331522}, Pst = {ppublish}, Title = {A role for cingulate pioneering axons in the development of the corpus callosum}, Volume = {434}, Year = {2001}} @article{Lee:2014, Abstract = {Sensory processing is dependent upon behavioral state. In mice, locomotion is accompanied by changes in cortical state and enhanced visual responses. Although recent studies have begun to elucidate intrinsic cortical mechanisms underlying this effect, the neural circuits that initially couple locomotion to cortical processing are unknown. The mesencephalic locomotor region (MLR) has been shown to be capable of initiating running and is associated with the ascending reticular activating system. Here, we find that optogenetic stimulation of the MLR in awake, head-fixed mice can induce both locomotion and increases in the gain of cortical responses. MLR stimulation below the threshold for overt movement similarly changed cortical processing, revealing that MLR's effects on cortex are dissociable from locomotion. Likewise, stimulation of MLR projections to the basal forebrain also enhanced cortical responses, suggesting a pathway linking the MLR to cortex. These studies demonstrate that the MLR regulates cortical state in parallel with locomotion.}, Author = {Lee, A Moses and Hoy, Jennifer L and Bonci, Antonello and Wilbrecht, Linda and Stryker, Michael P and Niell, Cristopher M}, Date-Added = {2014-10-09 12:55:29 +0000}, Date-Modified = {2014-10-09 12:55:29 +0000}, Doi = {10.1016/j.neuron.2014.06.031}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Brain Stem; Locomotion; Mesencephalon; Mice; Neural Pathways; Neurons; Photic Stimulation; Visual Cortex}, Month = {Jul}, Number = {2}, Pages = {455-66}, Pmc = {PMC4151326}, pmid = {25033185}, Pst = {ppublish}, Title = {Identification of a brainstem circuit regulating visual cortical state in parallel with locomotion}, Volume = {83}, Year = {2014}, url = {papers/Lee_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.06.031}} @article{Homae:2010, Abstract = {Human cognition and behaviors are subserved by global networks of neural mechanisms. Although the organization of the brain is a subject of interest, the process of development of global cortical networks in early infancy has not yet been clarified. In the present study, we explored developmental changes in these networks from several days to 6 months after birth by examining spontaneous fluctuations in brain activity, using multichannel near-infrared spectroscopy. We set up 94 measurement channels over the frontal, temporal, parietal, and occipital regions of the infant brain. The obtained signals showed complex time-series properties, which were characterized as 1/f fluctuations. To reveal the functional connectivity of the cortical networks, we calculated the temporal correlations of continuous signals between all the pairs of measurement channels. We found that the cortical network organization showed regional dependency and dynamic changes in the course of development. In the temporal, parietal, and occipital regions, connectivity increased between homologous regions in the two hemispheres and within hemispheres; in the frontal regions, it decreased progressively. Frontoposterior connectivity changed to a "U-shaped" pattern within 6 months: it decreases from the neonatal period to the age of 3 months and increases from the age of 3 months to the age of 6 months. We applied cluster analyses to the correlation coefficients and showed that the bilateral organization of the networks begins to emerge during the first 3 months of life. Our findings suggest that these developing networks, which form multiple clusters, are precursors of the functional cerebral architecture.}, Author = {Homae, Fumitaka and Watanabe, Hama and Otobe, Takayuki and Nakano, Tamami and Go, Tohshin and Konishi, Yukuo and Taga, Gentaro}, Date-Added = {2014-10-08 17:17:19 +0000}, Date-Modified = {2014-10-09 12:54:32 +0000}, Doi = {10.1523/JNEUROSCI.5618-09.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {resting-state connectivity; fMRI; network analysis; Graph theory; default mode network; human; development; birth}, Mesh = {Age Factors; Brain Mapping; Cerebral Cortex; Female; Humans; Infant; Infant, Newborn; Male; Nerve Net}, Month = {Apr}, Number = {14}, Pages = {4877-82}, pmid = {20371807}, Pst = {ppublish}, Title = {Development of global cortical networks in early infancy}, Volume = {30}, Year = {2010}, url = {papers/Homae_JNeurosci2010.pdf}} @article{Smyser:2010, Abstract = {Application of resting state functional connectivity magnetic resonance imaging (fcMRI) to the study of prematurely born infants enables assessment of the earliest forms of cerebral connectivity and characterization of its early development in the human brain. We obtained 90 longitudinal fcMRI data sets from a cohort of preterm infants aged from 26 weeks postmenstrual age (PMA) through term equivalent age at PMA-specific time points. Utilizing seed-based correlation analysis, we identified resting state networks involving varied cortical regions, the thalamus, and cerebellum. Identified networks demonstrated a regionally variable age-specific pattern of development, with more mature forms consisting of localized interhemispheric connections between homotopic counterparts. Anatomical distance was found to play a critical role in the rate of connection development. Prominent differences were noted between networks identified in term control versus premature infants at term equivalent, including in the thalamocortical connections critical for neurodevelopment. Putative precursors of the default mode network were detected in term control infants but were not identified in preterm infants, including those at term equivalent. Identified patterns of network maturation reflect the intricate relationship of structural and functional processes present throughout this important developmental period and are consistent with prior investigations of neurodevelopment in this population.}, Author = {Smyser, Christopher D and Inder, Terrie E and Shimony, Joshua S and Hill, Jason E and Degnan, Andrew J and Snyder, Abraham Z and Neil, Jeffrey J}, Date-Added = {2014-10-08 16:30:40 +0000}, Date-Modified = {2014-10-08 16:34:33 +0000}, Doi = {10.1093/cercor/bhq035}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {resting-state connectivity; fMRI; Human; network analysis; Graph theory; mirror symmetry; hemisphere; axon guidance; default mode network}, Mesh = {Brain; Female; Humans; Image Interpretation, Computer-Assisted; Infant, Newborn; Magnetic Resonance Imaging; Male; Nerve Net; Neurogenesis; Pregnancy; Premature Birth}, Month = {Dec}, Number = {12}, Pages = {2852-62}, Pmc = {PMC2978240}, pmid = {20237243}, Pst = {ppublish}, Title = {Longitudinal analysis of neural network development in preterm infants}, Volume = {20}, Year = {2010}, url = {papers/Smyser_CerebCortex2010.pdf}} @article{Colonnese:2014, Abstract = {The ability to generate behaviorally appropriate cortical network states is central to sensory perception and plasticity, but little is known about the timing and mechanisms of their development. I paired intracellular and extracellular recordings in the visual cortex of awake infant rats to determine the synaptic and circuit mechanisms regulating the development of a key network state, the persistent and stable subthreshold membrane potential (Vm) depolarization associated with wakefulness/alertness in cortical networks, called the "desynchronized" or "activated" state. Current-clamp recordings reveal that the desynchronized state is absent during the first 2 postnatal weeks, despite behavioral wakefulness. During this period, Vm remains at the resting membrane potential >80% of the time, regardless of behavioral state. Vm dynamics during spontaneous or light-evoked activity were highly variable, contained long-duration supratheshold plateau potentials, and high spike probability, suggesting an unstable and hyperexcitable early cortical network. Voltage-clamp recordings reveal that effective feedforward inhibition is absent at these early ages despite the presence of feedback inhibition. Stable membrane depolarization during wakefulness finally emerges 1-2 d before eye opening and is statistically indistinguishable from that in adults within days. Reduced cortical excitability, fast feedforward inhibition, and the slow cortical oscillation appear simultaneously with stable depolarization, suggesting that an absence of inhibitory balance during early development prevents the expression of the active state and hence a normal wakeful state in early cortex. These observations identify feedforward inhibition as a potential key regulator of cortical network activity development.}, Author = {Colonnese, Matthew T}, Date-Added = {2014-10-03 14:37:13 +0000}, Date-Modified = {2014-10-03 14:37:13 +0000}, Doi = {10.1523/JNEUROSCI.3659-13.2014}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Action Potentials; Age Factors; Animals; Animals, Newborn; Cerebral Cortex; Cortical Synchronization; Eye; Female; Light; Male; Nerve Net; Neural Inhibition; Neurons; Patch-Clamp Techniques; Rats; Rats, Long-Evans; Sleep; Visual Pathways; Wakefulness}, Month = {Apr}, Number = {16}, Pages = {5477-85}, Pmc = {PMC3988407}, pmid = {24741038}, Pst = {ppublish}, Title = {Rapid developmental emergence of stable depolarization during wakefulness by inhibitory balancing of cortical network excitability}, Volume = {34}, Year = {2014}, url = {papers/Colonnese_JNeurosci2014.pdf}} @article{Colonnese:2012, Abstract = {The immature brain spontaneously expresses unique patterns of electrical activity that are believed to contribute to the development of neuronal networks. Certain electrographic features of this activity, particularly modulation on an infraslow time scale, resemble activity patterns observed in the mature brain at 'rest', loosely defined as the absence of an investigator imposed task. However, it is not clear whether the immature activity patterns observed at rest are precursors of the spontaneous neuronal activity that forms resting state networks in the adult. Here, we review recent studies that have explored the generative mechanisms of resting state activity during development in the primary sensory systems of premature human neonates and neonatal rodents. The remarkable hypothesis suggested by this work is that while resting state activity during the pre- and possibly near-term period can bear superficial resemblance to adult activity it is fundamentally different in terms of function and origin. During early development spontaneous thalamocortical activity in primary sensory regions is determined largely by transitory generators in the sensory periphery. This is in contrast to the adult, where spontaneous activity generated within thalamocortex, particularly by cortico-cortical connections, dominates. We therefore suggest a conservative interpretation of developmental mapping studies which are based on indirect measurement of activity (e.g. fMRI), or on the partitioning of EEG frequency using bands derived from adult studies. The generative mechanisms for brain activity at early ages are likely different from those of adults, and may play very different roles; for example in circuit formation as opposed to attention.}, Author = {Colonnese, Matthew and Khazipov, Rustem}, Date-Added = {2014-10-03 14:32:38 +0000}, Date-Modified = {2014-10-03 14:36:15 +0000}, Doi = {10.1016/j.neuroimage.2012.02.046}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Keywords = {review literature; resting-state fMRI; default mode network; development; Human}, Mesh = {Animals; Brain; Brain Mapping; Humans; Magnetic Resonance Imaging; Rest}, Month = {Oct}, Number = {4}, Pages = {2212-21}, pmid = {22387472}, Pst = {ppublish}, Title = {Spontaneous activity in developing sensory circuits: Implications for resting state fMRI}, Volume = {62}, Year = {2012}, url = {papers/Colonnese_Neuroimage2012.pdf}} @article{Newman:2006, Abstract = {Many networks of interest in the sciences, including social networks, computer networks, and metabolic and regulatory networks, are found to divide naturally into communities or modules. The problem of detecting and characterizing this community structure is one of the outstanding issues in the study of networked systems. One highly effective approach is the optimization of the quality function known as "modularity" over the possible divisions of a network. Here I show that the modularity can be expressed in terms of the eigenvectors of a characteristic matrix for the network, which I call the modularity matrix, and that this expression leads to a spectral algorithm for community detection that returns results of demonstrably higher quality than competing methods in shorter running times. I illustrate the method with applications to several published network data sets.}, Author = {Newman, M E J}, Date-Added = {2014-10-02 19:57:45 +0000}, Date-Modified = {2014-10-02 19:58:32 +0000}, Doi = {10.1073/pnas.0601602103}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Graph theory; network analysis; Theoretical; Mathematics}, Month = {Jun}, Number = {23}, Pages = {8577-82}, Pmc = {PMC1482622}, pmid = {16723398}, Pst = {ppublish}, Title = {Modularity and community structure in networks}, Volume = {103}, Year = {2006}, url = {papers/Newman_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0601602103}} @article{Bonacich:2007, Author = {Bonacich, P}, Date-Added = {2014-10-01 22:01:09 +0000}, Date-Modified = {2014-10-01 22:04:10 +0000}, Journal = {Social Networks}, Keywords = {Graph theory; network analysis; Mathematics; Theoretical}, Pages = {555--564}, Title = {Some unique properties of eigenvector centrality}, Volume = {29}, Year = {2007}, url = {papers/Bonacich_SocialNetworks2007.pdf}} @article{Bonacich:1972, Author = {Bonacich, P}, Date-Added = {2014-10-01 21:53:37 +0000}, Date-Modified = {2014-10-01 21:56:19 +0000}, Journal = {Sociological Methodology}, Keywords = {Graph theory; network analysis; Mathematics; Theoretical}, Pages = {176--185}, Title = {Technique for Analyzing Overlapping Memberships}, Volume = {4}, Year = {1972}, url = {papers/Bonacich_SociologicalMethodology1972.pdf}} @article{Bonacich:1987, Author = {Bonacich, P}, Date-Added = {2014-10-01 21:51:14 +0000}, Date-Modified = {2014-10-01 21:52:27 +0000}, Journal = {American Journal of Sociology}, Keywords = {Graph theory; network analysis; Mathematics; Theoretical}, Pages = {1170-1182}, Title = {Power and Centrality: A Family of Measures}, Volume = {92}, Year = {1987}, url = {papers/Bonacich_AmericanJournalofSociology1987.pdf}} @article{Lohmann:2010, Abstract = {Functional magnetic resonance data acquired in a task-absent condition ("resting state") require new data analysis techniques that do not depend on an activation model. In this work, we introduce an alternative assumption- and parameter-free method based on a particular form of node centrality called eigenvector centrality. Eigenvector centrality attributes a value to each voxel in the brain such that a voxel receives a large value if it is strongly correlated with many other nodes that are themselves central within the network. Google's PageRank algorithm is a variant of eigenvector centrality. Thus far, other centrality measures - in particular "betweenness centrality" - have been applied to fMRI data using a pre-selected set of nodes consisting of several hundred elements. Eigenvector centrality is computationally much more efficient than betweenness centrality and does not require thresholding of similarity values so that it can be applied to thousands of voxels in a region of interest covering the entire cerebrum which would have been infeasible using betweenness centrality. Eigenvector centrality can be used on a variety of different similarity metrics. Here, we present applications based on linear correlations and on spectral coherences between fMRI times series. This latter approach allows us to draw conclusions of connectivity patterns in different spectral bands. We apply this method to fMRI data in task-absent conditions where subjects were in states of hunger or satiety. We show that eigenvector centrality is modulated by the state that the subjects were in. Our analyses demonstrate that eigenvector centrality is a computationally efficient tool for capturing intrinsic neural architecture on a voxel-wise level.}, Author = {Lohmann, Gabriele and Margulies, Daniel S and Horstmann, Annette and Pleger, Burkhard and Lepsien, Joeran and Goldhahn, Dirk and Schloegl, Haiko and Stumvoll, Michael and Villringer, Arno and Turner, Robert}, Date-Added = {2014-10-01 21:12:08 +0000}, Date-Modified = {2014-10-01 21:13:28 +0000}, Doi = {10.1371/journal.pone.0010232}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {Graph theory; network analysis; fMRI; resting-state connectivity; Human}, Mesh = {Algorithms; Brain Mapping; Humans; Hunger; Magnetic Resonance Imaging; Models, Neurological; Neural Pathways; Satiety Response}, Number = {4}, Pages = {e10232}, Pmc = {PMC2860504}, pmid = {20436911}, Pst = {epublish}, Title = {Eigenvector centrality mapping for analyzing connectivity patterns in fMRI data of the human brain}, Volume = {5}, Year = {2010}, url = {papers/Lohmann_PLoSOne2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0010232}} @article{Kamada:1989, Author = {Kamada, T. and Kawai, S}, Date-Added = {2014-10-01 20:02:32 +0000}, Date-Modified = {2014-10-01 20:03:56 +0000}, Journal = {Information Processing Letters}, Number = {1}, Pages = {7-15}, Title = {An Algorithm for Drawing General Undirected Graphs}, Volume = {31}, Year = {1989}, url = {papers/Kamada_InformationProcessingLetters1989.pdf}} @article{Fruchterman:1991, Author = {Fruchterman, T.M.J. and Reingold, E.M.}, Date-Added = {2014-10-01 20:00:19 +0000}, Date-Modified = {2014-10-01 20:01:56 +0000}, Journal = {Software - Practice and Experience}, Number = {11}, Pages = {1129-1164}, Title = {Graph Drawing by Force-directed Placement}, Volume = {21}, Year = {1991}, url = {papers/Fruchterman_Software-PracticeandExperience1991.pdf}} @article{Stevens:2009, Abstract = {This study examined how the mutual interactions of functionally integrated neural networks during resting-state fMRI differed between adolescence and adulthood. Independent component analysis (ICA) was used to identify functionally connected neural networks in 100 healthy participants aged 12-30 years. Hemodynamic timecourses that represented integrated neural network activity were analyzed with tools that quantified system "causal density" estimates, which indexed the proportion of significant Granger causality relationships among system nodes. Mutual influences among networks decreased with age, likely reflecting stronger within-network connectivity and more efficient between-network influences with greater development. Supplemental tests showed that this normative age-related reduction in causal density was accompanied by fewer significant connections to and from each network, regional increases in the strength of functional integration within networks, and age-related reductions in the strength of numerous specific system interactions. The latter included paths between lateral prefrontal-parietal circuits and "default mode" networks. These results contribute to an emerging understanding that activity in widely distributed networks thought to underlie complex cognition influences activity in other networks.}, Author = {Stevens, Michael C and Pearlson, Godfrey D and Calhoun, Vince D}, Date-Added = {2014-09-26 21:18:24 +0000}, Date-Modified = {2014-09-26 21:19:08 +0000}, Doi = {10.1002/hbm.20673}, Journal = {Hum Brain Mapp}, Journal-Full = {Human brain mapping}, Keywords = {resting-state fMRI; connectivity; development; human; default mode network; Human; Child; development}, Mesh = {Adolescent; Adolescent Development; Adult; Aging; Brain; Child; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways; Regression Analysis; Rest; Young Adult}, Month = {Aug}, Number = {8}, Pages = {2356-66}, pmid = {19172655}, Pst = {ppublish}, Title = {Changes in the interaction of resting-state neural networks from adolescence to adulthood}, Volume = {30}, Year = {2009}, url = {papers/Stevens_HumBrainMapp2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/hbm.20673}} @article{Cao:2014, Abstract = {Human brain function undergoes complex transformations across the lifespan. We employed resting-state functional MRI and graph-theory approaches to systematically chart the lifespan trajectory of the topological organization of human whole-brain functional networks in 126 healthy individuals ranging in age from 7 to 85 years. Brain networks were constructed by computing Pearson's correlations in blood-oxygenation-level-dependent temporal fluctuations among 1024 parcellation units followed by graph-based network analyses. We observed that the human brain functional connectome exhibited highly preserved non-random modular and rich club organization over the entire age range studied. Further quantitative analyses revealed linear decreases in modularity and inverted-U shaped trajectories of local efficiency and rich club architecture. Regionally heterogeneous age effects were mainly located in several hubs (e.g., default network, dorsal attention regions). Finally, we observed inverse trajectories of long- and short-distance functional connections, indicating that the reorganization of connectivity concentrates and distributes the brain's functional networks. Our results demonstrate topological changes in the whole-brain functional connectome across nearly the entire human lifespan, providing insights into the neural substrates underlying individual variations in behavior and cognition. These results have important implications for disease connectomics because they provide a baseline for evaluating network impairments in age-related neuropsychiatric disorders.}, Author = {Cao, Miao and Wang, Jin-Hui and Dai, Zheng-Jia and Cao, Xiao-Yan and Jiang, Li-Li and Fan, Feng-Mei and Song, Xiao-Wei and Xia, Ming-Rui and Shu, Ni and Dong, Qi and Milham, Michael P and Castellanos, F Xavier and Zuo, Xi-Nian and He, Yong}, Date-Added = {2014-09-26 21:15:20 +0000}, Date-Modified = {2014-09-26 21:16:24 +0000}, Doi = {10.1016/j.dcn.2013.11.004}, Journal = {Dev Cogn Neurosci}, Journal-Full = {Developmental cognitive neuroscience}, Keywords = {Functional connectomics; Graph theory; Lifespan trajectory; Rich club; network analysis; resting-state fMRI; human; adult; development; Child}, Mesh = {Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Aging; Brain; Brain Mapping; Child; Cognition; Connectome; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Sex Factors}, Month = {Jan}, Pages = {76-93}, pmid = {24333927}, Pst = {ppublish}, Title = {Topological organization of the human brain functional connectome across the lifespan}, Volume = {7}, Year = {2014}, url = {papers/Cao_DevCognNeurosci2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.dcn.2013.11.004}} @article{He:2009, Abstract = {The characterization of topological architecture of complex brain networks is one of the most challenging issues in neuroscience. Slow (<0.1 Hz), spontaneous fluctuations of the blood oxygen level dependent (BOLD) signal in functional magnetic resonance imaging are thought to be potentially important for the reflection of spontaneous neuronal activity. Many studies have shown that these fluctuations are highly coherent within anatomically or functionally linked areas of the brain. However, the underlying topological mechanisms responsible for these coherent intrinsic or spontaneous fluctuations are still poorly understood. Here, we apply modern network analysis techniques to investigate how spontaneous neuronal activities in the human brain derived from the resting-state BOLD signals are topologically organized at both the temporal and spatial scales. We first show that the spontaneous brain functional networks have an intrinsically cohesive modular structure in which the connections between regions are much denser within modules than between them. These identified modules are found to be closely associated with several well known functionally interconnected subsystems such as the somatosensory/motor, auditory, attention, visual, subcortical, and the "default" system. Specifically, we demonstrate that the module-specific topological features can not be captured by means of computing the corresponding global network parameters, suggesting a unique organization within each module. Finally, we identify several pivotal network connectors and paths (predominantly associated with the association and limbic/paralimbic cortex regions) that are vital for the global coordination of information flow over the whole network, and we find that their lesions (deletions) critically affect the stability and robustness of the brain functional system. Together, our results demonstrate the highly organized modular architecture and associated topological properties in the temporal and spatial brain functional networks of the human brain that underlie spontaneous neuronal dynamics, which provides important implications for our understanding of how intrinsically coherent spontaneous brain activity has evolved into an optimal neuronal architecture to support global computation and information integration in the absence of specific stimuli or behaviors.}, Author = {He, Yong and Wang, Jinhui and Wang, Liang and Chen, Zhang J and Yan, Chaogan and Yang, Hong and Tang, Hehan and Zhu, Chaozhe and Gong, Qiyong and Zang, Yufeng and Evans, Alan C}, Date-Added = {2014-09-26 20:52:03 +0000}, Date-Modified = {2014-09-26 20:53:42 +0000}, Doi = {10.1371/journal.pone.0005226}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {resting-state fMRI; human; Spontaneous activity; default mode network; connectivity; graph theory; network analysis}, Mesh = {Brain; Humans; Reproducibility of Results}, Number = {4}, Pages = {e5226}, Pmc = {PMC2668183}, pmid = {19381298}, Pst = {ppublish}, Title = {Uncovering intrinsic modular organization of spontaneous brain activity in humans}, Volume = {4}, Year = {2009}, url = {papers/He_PLoSOne2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0005226}} @article{Andrews-Hanna:2010, Abstract = {One of the most consistent observations in human functional imaging is that a network of brain regions referred to as the "default network" increases its activity during passive states. Here we explored the anatomy and function of the default network across three studies to resolve divergent hypotheses about its contributions to spontaneous cognition and active forms of decision making. Analysis of intrinsic activity revealed the network comprises multiple, dissociated components. A midline core (posterior cingulate and anterior medial prefrontal cortex) is active when people make self-relevant, affective decisions. In contrast, a medial temporal lobe subsystem becomes engaged when decisions involve constructing a mental scene based on memory. During certain experimentally directed and spontaneous acts of future-oriented thought, these dissociated components are simultaneously engaged, presumably to facilitate construction of mental models of personally significant events.}, Author = {Andrews-Hanna, Jessica R and Reidler, Jay S and Sepulcre, Jorge and Poulin, Renee and Buckner, Randy L}, Date-Added = {2014-09-26 20:10:24 +0000}, Date-Modified = {2014-09-26 20:12:28 +0000}, Doi = {10.1016/j.neuron.2010.02.005}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {resting-state fMRI; default mode network; human; network analysis; graph theory; Adult; connectivity}, Mesh = {Adolescent; Adult; Analysis of Variance; Brain; Brain Mapping; Cluster Analysis; Cognition; Emotions; Female; Humans; Image Processing, Computer-Assisted; Imagination; Magnetic Resonance Imaging; Male; Memory; Nerve Net; Neuropsychological Tests}, Month = {Feb}, Number = {4}, Pages = {550-62}, Pmc = {PMC2848443}, pmid = {20188659}, Pst = {ppublish}, Title = {Functional-anatomic fractionation of the brain's default network}, Volume = {65}, Year = {2010}, url = {papers/Andrews-Hanna_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.02.005}} @article{Thomason:2014, Abstract = {The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA≥31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.}, Author = {Thomason, Moriah E and Brown, Jesse A and Dassanayake, Maya T and Shastri, Rupal and Marusak, Hilary A and Hernandez-Andrade, Edgar and Yeo, Lami and Mody, Swati and Berman, Susan and Hassan, Sonia S and Romero, Roberto}, Date-Added = {2014-09-26 18:19:58 +0000}, Date-Modified = {2014-09-26 18:19:58 +0000}, Doi = {10.1371/journal.pone.0094423}, Journal = {PLoS One}, Journal-Full = {PloS one}, Number = {5}, Pages = {e94423}, Pmc = {PMC4006774}, pmid = {24788455}, Pst = {epublish}, Title = {Intrinsic functional brain architecture derived from graph theoretical analysis in the human fetus}, Volume = {9}, Year = {2014}, url = {papers/Thomason_PLoSOne2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0094423}} @article{Thomason:2013, Abstract = {Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.}, Author = {Thomason, Moriah E and Dassanayake, Maya T and Shen, Stephen and Katkuri, Yashwanth and Alexis, Mitchell and Anderson, Amy L and Yeo, Lami and Mody, Swati and Hernandez-Andrade, Edgar and Hassan, Sonia S and Studholme, Colin and Jeong, Jeong-Won and Romero, Roberto}, Date-Added = {2014-09-26 17:28:35 +0000}, Date-Modified = {2014-09-26 17:29:34 +0000}, Doi = {10.1126/scitranslmed.3004978}, Journal = {Sci Transl Med}, Journal-Full = {Science translational medicine}, Keywords = {human; fetal; fMRI; resting-state connectivity; default mode network; hemisphere; activity-development; wholeBrain}, Mesh = {Brain; Female; Humans; Magnetic Resonance Imaging; Neural Pathways; Pregnancy}, Month = {Feb}, Number = {173}, Pages = {173ra24}, Pmc = {PMC3618956}, pmid = {23427244}, Pst = {ppublish}, Title = {Cross-hemispheric functional connectivity in the human fetal brain}, Volume = {5}, Year = {2013}, url = {papers/Thomason_SciTranslMed2013.pdf}, Bdsk-File-2 = {papers/Thomason_SciTranslMed2013a.pdf}} @article{Zuo:2012, Abstract = {The network architecture of functional connectivity within the human brain connectome is poorly understood at the voxel level. Here, using resting state functional magnetic resonance imaging data from 1003 healthy adults, we investigate a broad array of network centrality measures to provide novel insights into connectivity within the whole-brain functional network (i.e., the functional connectome). We first assemble and visualize the voxel-wise (4 mm) functional connectome as a functional network. We then demonstrate that each centrality measure captures different aspects of connectivity, highlighting the importance of considering both global and local connectivity properties of the functional connectome. Beyond "detecting functional hubs," we treat centrality as measures of functional connectivity within the brain connectome and demonstrate their reliability and phenotypic correlates (i.e., age and sex). Specifically, our analyses reveal age-related decreases in degree centrality, but not eigenvector centrality, within precuneus and posterior cingulate regions. This implies that while local or (direct) connectivity decreases with age, connections with hub-like regions within the brain remain stable with age at a global level. In sum, these findings demonstrate the nonredundancy of various centrality measures and raise questions regarding their underlying physiological mechanisms that may be relevant to the study of neurodegenerative and psychiatric disorders.}, Author = {Zuo, Xi-Nian and Ehmke, Ross and Mennes, Maarten and Imperati, Davide and Castellanos, F Xavier and Sporns, Olaf and Milham, Michael P}, Date-Added = {2014-09-23 16:31:59 +0000}, Date-Modified = {2014-09-23 16:34:14 +0000}, Doi = {10.1093/cercor/bhr269}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {resting-state fMRI; connectivity; graph theory; network analysis; Human; adult}, Mesh = {Adult; Aging; Algorithms; Brain; Brain Mapping; Female; Humans; Magnetic Resonance Imaging; Male; Nerve Net; Neural Pathways; Sex Characteristics}, Month = {Aug}, Number = {8}, Pages = {1862-75}, pmid = {21968567}, Pst = {ppublish}, Title = {Network centrality in the human functional connectome}, Volume = {22}, Year = {2012}, url = {papers/Zuo_CerebCortex2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhr269}} @article{Heuvel:2009, Abstract = {During rest, multiple cortical brain regions are functionally linked forming resting-state networks. This high level of functional connectivity within resting-state networks suggests the existence of direct neuroanatomical connections between these functionally linked brain regions to facilitate the ongoing interregional neuronal communication. White matter tracts are the structural highways of our brain, enabling information to travel quickly from one brain region to another region. In this study, we examined both the functional and structural connections of the human brain in a group of 26 healthy subjects, combining 3 Tesla resting-state functional magnetic resonance imaging time-series with diffusion tensor imaging scans. Nine consistently found functionally linked resting-state networks were retrieved from the resting-state data. The diffusion tensor imaging scans were used to reconstruct the white matter pathways between the functionally linked brain areas of these resting-state networks. Our results show that well-known anatomical white matter tracts interconnect at least eight of the nine commonly found resting-state networks, including the default mode network, the core network, primary motor and visual network, and two lateralized parietal-frontal networks. Our results suggest that the functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain.}, Author = {van den Heuvel, Martijn P and Mandl, Ren{\'e} C W and Kahn, Ren{\'e} S and Hulshoff Pol, Hilleke E}, Date-Added = {2014-09-23 16:23:45 +0000}, Date-Modified = {2014-09-23 16:24:41 +0000}, Doi = {10.1002/hbm.20737}, Journal = {Hum Brain Mapp}, Journal-Full = {Human brain mapping}, Keywords = {resting-state fMRI; connectivity; network analysis; graph theory; human; adult}, Mesh = {Adolescent; Adult; Brain; Brain Mapping; Diffusion Magnetic Resonance Imaging; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Models, Neurological; Nerve Fibers, Myelinated; Nerve Net; Neural Pathways; Oxygen; Rest; Young Adult}, Month = {Oct}, Number = {10}, Pages = {3127-41}, pmid = {19235882}, Pst = {ppublish}, Title = {Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain}, Volume = {30}, Year = {2009}, url = {papers/Heuvel_HumBrainMapp2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/hbm.20737}} @article{Damoiseaux:2006, Abstract = {Functional MRI (fMRI) can be applied to study the functional connectivity of the human brain. It has been suggested that fluctuations in the blood oxygenation level-dependent (BOLD) signal during rest reflect the neuronal baseline activity of the brain, representing the state of the human brain in the absence of goal-directed neuronal action and external input, and that these slow fluctuations correspond to functionally relevant resting-state networks. Several studies on resting fMRI have been conducted, reporting an apparent similarity between the identified patterns. The spatial consistency of these resting patterns, however, has not yet been evaluated and quantified. In this study, we apply a data analysis approach called tensor probabilistic independent component analysis to resting-state fMRI data to find coherencies that are consistent across subjects and sessions. We characterize and quantify the consistency of these effects by using a bootstrapping approach, and we estimate the BOLD amplitude modulation as well as the voxel-wise cross-subject variation. The analysis found 10 patterns with potential functional relevance, consisting of regions known to be involved in motor function, visual processing, executive functioning, auditory processing, memory, and the so-called default-mode network, each with BOLD signal changes up to 3%. In general, areas with a high mean percentage BOLD signal are consistent and show the least variation around the mean. These findings show that the baseline activity of the brain is consistent across subjects exhibiting significant temporal dynamics, with percentage BOLD signal change comparable with the signal changes found in task-related experiments.}, Author = {Damoiseaux, J S and Rombouts, S A R B and Barkhof, F and Scheltens, P and Stam, C J and Smith, S M and Beckmann, C F}, Date-Added = {2014-09-23 16:15:01 +0000}, Date-Modified = {2014-09-23 16:22:19 +0000}, Doi = {10.1073/pnas.0601417103}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {resting-state fMRI; connectivity; default mode network; network; human}, Mesh = {Brain; Brain Mapping; Health; Humans; Magnetic Resonance Imaging; Rest}, Month = {Sep}, Number = {37}, Pages = {13848-53}, Pmc = {PMC1564249}, pmid = {16945915}, Pst = {ppublish}, Title = {Consistent resting-state networks across healthy subjects}, Volume = {103}, Year = {2006}, url = {papers/Damoiseaux_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0601417103}} @article{Salvador:2005, Abstract = {We investigated large-scale systems organization of the whole human brain using functional magnetic resonance imaging (fMRI) data acquired from healthy volunteers in a no-task or 'resting' state. Images were parcellated using a prior anatomical template, yielding regional mean time series for each of 90 regions (major cortical gyri and subcortical nuclei) in each subject. Significant pairwise functional connections, defined by the group mean inter-regional partial correlation matrix, were mostly either local and intrahemispheric or symmetrically interhemispheric. Low-frequency components in the time series subtended stronger inter-regional correlations than high-frequency components. Intrahemispheric connectivity was generally related to anatomical distance by an inverse square law; many symmetrical interhemispheric connections were stronger than predicted by the anatomical distance between bilaterally homologous regions. Strong interhemispheric connectivity was notably absent in data acquired from a single patient, minimally conscious following a brainstem lesion. Multivariate analysis by hierarchical clustering and multidimensional scaling consistently defined six major systems in healthy volunteers-- corresponding approximately to four neocortical lobes, medial temporal lobe and subcortical nuclei- - that could be further decomposed into anatomically and functionally plausible subsystems, e.g. dorsal and ventral divisions of occipital cortex. An undirected graph derived by thresholding the healthy group mean partial correlation matrix demonstrated local clustering or cliquishness of connectivity and short mean path length compatible with prior data on small world characteristics of non-human cortical anatomy. Functional MRI demonstrates a neurophysiological architecture of the normal human brain that is anatomically sensible, strongly symmetrical, disrupted by acute brain injury, subtended predominantly by low frequencies and consistent with a small world network topology.}, Author = {Salvador, Raymond and Suckling, John and Coleman, Martin R and Pickard, John D and Menon, David and Bullmore, Ed}, Date-Added = {2014-09-23 16:01:55 +0000}, Date-Modified = {2014-09-23 16:02:57 +0000}, Doi = {10.1093/cercor/bhi016}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {resting-state fMRI; connectivity; graph theory; network analysis; Neocortex; Human; default mode network}, Mesh = {Adult; Algorithms; Brain; Brain Stem; Cerebral Cortex; Cerebrovascular Circulation; Cluster Analysis; Echo-Planar Imaging; Female; Functional Laterality; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Models, Neurological; Multivariate Analysis; Nerve Net}, Month = {Sep}, Number = {9}, Pages = {1332-42}, pmid = {15635061}, Pst = {ppublish}, Title = {Neurophysiological architecture of functional magnetic resonance images of human brain}, Volume = {15}, Year = {2005}, url = {papers/Salvador_CerebCortex2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhi016}} @article{Fair:2009, Abstract = {The mature human brain is organized into a collection of specialized functional networks that flexibly interact to support various cognitive functions. Studies of development often attempt to identify the organizing principles that guide the maturation of these functional networks. In this report, we combine resting state functional connectivity MRI (rs-fcMRI), graph analysis, community detection, and spring-embedding visualization techniques to analyze four separate networks defined in earlier studies. As we have previously reported, we find, across development, a trend toward 'segregation' (a general decrease in correlation strength) between regions close in anatomical space and 'integration' (an increased correlation strength) between selected regions distant in space. The generalization of these earlier trends across multiple networks suggests that this is a general developmental principle for changes in functional connectivity that would extend to large-scale graph theoretic analyses of large-scale brain networks. Communities in children are predominantly arranged by anatomical proximity, while communities in adults predominantly reflect functional relationships, as defined from adult fMRI studies. In sum, over development, the organization of multiple functional networks shifts from a local anatomical emphasis in children to a more "distributed" architecture in young adults. We argue that this "local to distributed" developmental characterization has important implications for understanding the development of neural systems underlying cognition. Further, graph metrics (e.g., clustering coefficients and average path lengths) are similar in child and adult graphs, with both showing "small-world"-like properties, while community detection by modularity optimization reveals stable communities within the graphs that are clearly different between young children and young adults. These observations suggest that early school age children and adults both have relatively efficient systems that may solve similar information processing problems in divergent ways.}, Author = {Fair, Damien A and Cohen, Alexander L and Power, Jonathan D and Dosenbach, Nico U F and Church, Jessica A and Miezin, Francis M and Schlaggar, Bradley L and Petersen, Steven E}, Date-Added = {2014-09-22 20:50:37 +0000}, Date-Modified = {2014-09-22 20:53:22 +0000}, Doi = {10.1371/journal.pcbi.1000381}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {resting-state fMRI; connectivity; graph theory; network analysis; human; development; Child; Adult; default mode network}, Mesh = {Adolescent; Adult; Brain; Child; Humans; Magnetic Resonance Imaging; Models, Neurological; Nerve Net; Neural Pathways}, Month = {May}, Number = {5}, Pages = {e1000381}, Pmc = {PMC2671306}, pmid = {19412534}, Pst = {ppublish}, Title = {Functional brain networks develop from a "local to distributed" organization}, Volume = {5}, Year = {2009}, url = {papers/Fair_PLoSComputBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.1000381}} @article{Gao:2009, Abstract = {Several lines of evidence have implicated the existence of the brain's default network during passive or undirected mental states. Nevertheless, results on the emergence of the default network in very young pediatric subjects are lacking. Using resting functional magnetic resonance imaging in healthy pediatric subjects between 2 weeks and 2 years of age, we describe the temporal evolution of the default network in a critical, previously unstudied, period of early human brain development. Our results demonstrate that a primitive and incomplete default network is present in 2-week-olds, followed by a marked increase in the number of brain regions exhibiting connectivity, and the percent of connection at 1 year of age. By 2 years of age, the default network becomes similar to that observed in adults, including medial prefrontal cortex (MPFC), posterior cingulate cortex/retrosplenial (PCC/Rsp), inferior parietal lobule, lateral temporal cortex, and hippocampus regions. While the anatomical representations of the default network highly depend on age, the PCC/Rsp is consistently observed at in both age groups and is central to the most and strongest connections of the default network, suggesting that PCC/Rsp may serve as the main "hub" of the default network as this region does in adults. In addition, although not as remarkable as the PCC/Rsp, the MPFC also emerges as a potential secondary hub starting from 1 year of age. These findings reveal the temporal development of the default network in the critical period of early brain development and offer new insights into the emergence of brain default network.}, Author = {Gao, Wei and Zhu, Hongtu and Giovanello, Kelly S and Smith, J Keith and Shen, Dinggang and Gilmore, John H and Lin, Weili}, Date-Added = {2014-09-22 20:28:02 +0000}, Date-Modified = {2014-09-22 20:28:02 +0000}, Doi = {10.1073/pnas.0811221106}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Adult; Age Distribution; Brain; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Nerve Net}, Month = {Apr}, Number = {16}, Pages = {6790-5}, Pmc = {PMC2672537}, pmid = {19351894}, Pst = {ppublish}, Title = {Evidence on the emergence of the brain's default network from 2-week-old to 2-year-old healthy pediatric subjects}, Volume = {106}, Year = {2009}, url = {papers/Gao_ProcNatlAcadSciUSA2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0811221106}} @article{Goldman-Rakic:1988, Author = {Goldman-Rakic, P S}, Date-Added = {2014-09-22 20:17:48 +0000}, Date-Modified = {2014-09-22 20:17:48 +0000}, Doi = {10.1146/annurev.ne.11.030188.001033}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Mesh = {Animals; Association; Cerebral Cortex; Cognition; Humans; Neural Pathways; Primates; Psychomotor Performance}, Pages = {137-56}, pmid = {3284439}, Pst = {ppublish}, Title = {Topography of cognition: parallel distributed networks in primate association cortex}, Volume = {11}, Year = {1988}, url = {papers/Goldman-Rakic_AnnuRevNeurosci1988.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.ne.11.030188.001033}} @article{Shi:2012, Abstract = {Recently, an increasing body of evidence suggests that developmental abnormalities related to schizophrenia may occur as early as the neonatal stage. Impairments of brain gray matter and wiring problems of axonal fibers are commonly suspected to be responsible for the disconnection hypothesis in schizophrenia adults, but significantly less is known in neonates. In this study, we investigated 26 neonates who were at genetic risk for schizophrenia and 26 demographically matched healthy neonates using both morphological and white matter networks to examine possible brain connectivity abnormalities. The results showed that both populations exhibited small-world network topology. Morphological network analysis indicated that the brain structural associations of the high-risk neonates tended to have globally lower efficiency, longer connection distance, and less number of hub nodes and edges with relatively higher betweenness. Subgroup analysis showed that male neonates were significantly disease-affected, while the female neonates were not. White matter network analysis, however, showed that the fiber networks were globally unaffected, although several subcortical-cortical connections had significantly less number of fibers in high-risk neonates. This study provides new lines of evidence in support of the disconnection hypothesis, reinforcing the notion that the genetic risk of schizophrenia induces alterations in both gray matter structural associations and white matter connectivity.}, Author = {Shi, Feng and Yap, Pew-Thian and Gao, Wei and Lin, Weili and Gilmore, John H and Shen, Dinggang}, Date-Added = {2014-09-22 20:12:06 +0000}, Date-Modified = {2014-09-22 20:12:54 +0000}, Doi = {10.1016/j.neuroimage.2012.05.026}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Keywords = {structural connectivity; DTI; infant; Human; development; Schizophrenia; graph theory; network analysis}, Mesh = {Brain; Diffusion Magnetic Resonance Imaging; Female; Genetic Predisposition to Disease; Humans; Image Interpretation, Computer-Assisted; Infant, Newborn; Male; Neural Pathways; Risk Factors; Schizophrenia}, Month = {Sep}, Number = {3}, Pages = {1622-33}, Pmc = {PMC3408572}, pmid = {22613620}, Pst = {ppublish}, Title = {Altered structural connectivity in neonates at genetic risk for schizophrenia: a combined study using morphological and white matter networks}, Volume = {62}, Year = {2012}, url = {papers/Shi_Neuroimage2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2012.05.026}} @article{Hagmann:2010, Abstract = {From toddler to late teenager, the macroscopic pattern of axonal projections in the human brain remains largely unchanged while undergoing dramatic functional modifications that lead to network refinement. These functional modifications are mediated by increasing myelination and changes in axonal diameter and synaptic density, as well as changes in neurochemical mediators. Here we explore the contribution of white matter maturation to the development of connectivity between ages 2 and 18 y using high b-value diffusion MRI tractography and connectivity analysis. We measured changes in connection efficacy as the inverse of the average diffusivity along a fiber tract. We observed significant refinement in specific metrics of network topology, including a significant increase in node strength and efficiency along with a decrease in clustering. Major structural modules and hubs were in place by 2 y of age, and they continued to strengthen their profile during subsequent development. Recording resting-state functional MRI from a subset of subjects, we confirmed a positive correlation between structural and functional connectivity, and in addition observed that this relationship strengthened with age. Continuously increasing integration and decreasing segregation of structural connectivity with age suggests that network refinement mediated by white matter maturation promotes increased global efficiency. In addition, the strengthening of the correlation between structural and functional connectivity with age suggests that white matter connectivity in combination with other factors, such as differential modulation of axonal diameter and myelin thickness, that are partially captured by inverse average diffusivity, play an increasingly important role in creating brain-wide coherence and synchrony.}, Author = {Hagmann, P and Sporns, O and Madan, N and Cammoun, L and Pienaar, R and Wedeen, V J and Meuli, R and Thiran, J-P and Grant, P E}, Date-Added = {2014-09-22 20:08:39 +0000}, Date-Modified = {2014-09-22 20:10:57 +0000}, Doi = {10.1073/pnas.1009073107}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {graph theory; network analysis; structural connectivity; resting-state fMRI; DTI; Human; Child; Development}, Mesh = {Adolescent; Adolescent Development; Axons; Cerebral Cortex; Child; Child Development; Child, Preschool; Female; Follow-Up Studies; Humans; Infant; Magnetic Resonance Imaging; Male; Myelin Sheath; Synapses}, Month = {Nov}, Number = {44}, Pages = {19067-72}, Pmc = {PMC2973853}, pmid = {20956328}, Pst = {ppublish}, Title = {White matter maturation reshapes structural connectivity in the late developing human brain}, Volume = {107}, Year = {2010}, url = {papers/Hagmann_ProcNatlAcadSciUSA2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1009073107}} @article{Supekar:2009, Abstract = {The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at the global level, they differ significantly in hierarchical organization and interregional connectivity. We found that subcortical areas were more strongly connected with primary sensory, association, and paralimbic areas in children, whereas young-adults showed stronger cortico-cortical connectivity between paralimbic, limbic, and association areas. Further, combined analysis of functional connectivity with wiring distance measures derived from white-matter fiber tracking revealed that the development of large-scale brain networks is characterized by weakening of short-range functional connectivity and strengthening of long-range functional connectivity. Importantly, our findings show that the dynamic process of over-connectivity followed by pruning, which rewires connectivity at the neuronal level, also operates at the systems level, helping to reconfigure and rebalance subcortical and paralimbic connectivity in the developing brain. Our study demonstrates the usefulness of network analysis of brain connectivity to elucidate key principles underlying functional brain maturation, paving the way for novel studies of disrupted brain connectivity in neurodevelopmental disorders such as autism.}, Author = {Supekar, Kaustubh and Musen, Mark and Menon, Vinod}, Date-Added = {2014-09-22 20:03:33 +0000}, Date-Modified = {2014-09-22 20:07:33 +0000}, Doi = {10.1371/journal.pbio.1000157}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {resting-state fMRI; connectivity; graph theory; network analysis; Human; Child; development; default mode network}, Mesh = {Brain; Brain Mapping; Cerebral Cortex; Child; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Models, Neurological; Nerve Net; Neural Pathways; Young Adult}, Month = {Jul}, Number = {7}, Pages = {e1000157}, Pmc = {PMC2705656}, pmid = {19621066}, Pst = {ppublish}, Title = {Development of large-scale functional brain networks in children}, Volume = {7}, Year = {2009}, url = {papers/Supekar_PLoSBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1000157}} @article{Uddin:2011, Abstract = {Brain structural and functional development, throughout childhood and into adulthood, underlies the maturation of increasingly sophisticated cognitive abilities. High-level attentional and cognitive control processes rely on the integrity of, and dynamic interactions between, core neurocognitive networks. The right fronto-insular cortex (rFIC) is a critical component of a salience network (SN) that mediates interactions between large-scale brain networks involved in externally oriented attention [central executive network (CEN)] and internally oriented cognition [default mode network (DMN)]. How these systems reconfigure and mature with development is a critical question for cognitive neuroscience, with implications for neurodevelopmental pathologies affecting brain connectivity. Using functional and effective connectivity measures applied to fMRI data, we examine interactions within and between the SN, CEN, and DMN. We find that functional coupling between key network nodes is stronger in adults than in children, as are causal links emanating from the rFIC. Specifically, the causal influence of the rFIC on nodes of the SN and CEN was significantly greater in adults compared with children. Notably, these results were entirely replicated on an independent dataset of matched children and adults. Developmental changes in functional and effective connectivity were related to structural connectivity along these links. Diffusion tensor imaging tractography revealed increased structural integrity in adults compared with children along both within- and between-network pathways associated with the rFIC. These results suggest that structural and functional maturation of rFIC pathways is a critical component of the process by which human brain networks mature during development to support complex, flexible cognitive processes in adulthood.}, Author = {Uddin, Lucina Q and Supekar, Kaustubh S and Ryali, Srikanth and Menon, Vinod}, Date-Added = {2014-09-22 19:46:26 +0000}, Date-Modified = {2014-09-22 19:47:35 +0000}, Doi = {10.1523/JNEUROSCI.4465-11.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {resting-state fMRI; connectivity; human; Child; default mode network; Attention; Decision Making; graph theory; network analysis}, Mesh = {Brain; Brain Mapping; Child; Cognition; Diffusion Tensor Imaging; Female; Frontal Lobe; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Nerve Net; Young Adult}, Month = {Dec}, Number = {50}, Pages = {18578-89}, Pmc = {PMC3641286}, pmid = {22171056}, Pst = {ppublish}, Title = {Dynamic reconfiguration of structural and functional connectivity across core neurocognitive brain networks with development}, Volume = {31}, Year = {2011}, url = {papers/Uddin_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4465-11.2011}} @article{Hwang:2013, Abstract = {Functional hubs are brain regions that play a crucial role in facilitating communication among parallel, distributed brain networks. The developmental emergence and stability of hubs, however, is not well understood. The current study used measures of network topology drawn from graph theory to investigate the development of functional hubs in 99 participants, 10-20 years of age. We found that hub architecture was evident in late childhood and was stable from adolescence to early adulthood. Connectivity between hub and non-hub ("spoke") regions, however, changed with development. From childhood to adolescence, the strength of connections between frontal hubs and cortical and subcortical spoke regions increased. From adolescence to adulthood, hub-spoke connections with frontal hubs were stable, whereas connectivity between cerebellar hubs and cortical spoke regions increased. Our findings suggest that a developmentally stable functional hub architecture provides the foundation of information flow in the brain, whereas connections between hubs and spokes continue to develop, possibly supporting mature cognitive function.}, Author = {Hwang, Kai and Hallquist, Michael N and Luna, Beatriz}, Date-Added = {2014-09-22 19:43:42 +0000}, Date-Modified = {2014-09-22 19:44:06 +0000}, Doi = {10.1093/cercor/bhs227}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {adolescents; brain networks; development; functional connectivity; graph theory; default mode network; human; resting-state fMRI}, Mesh = {Adolescent; Brain; Child; Humans; Magnetic Resonance Imaging; Models, Neurological; Nerve Net; Neural Pathways; Rest; Young Adult}, Month = {Oct}, Number = {10}, Pages = {2380-93}, Pmc = {PMC3767958}, pmid = {22875861}, Pst = {ppublish}, Title = {The development of hub architecture in the human functional brain network}, Volume = {23}, Year = {2013}, url = {papers/Hwang_CerebCortex2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhs227}} @article{Fransson:2011, Abstract = {The functional network topology of the adult human brain has recently begun to be noninvasively mapped using resting-state functional connectivity magnetic resonance imaging and described using mathematical tools originating from graph theory. Previous studies have revealed the existence of disproportionally connected brain regions, so called cortical hubs, which act as information convergence zones and supposedly capture key aspects of how the brain's architecture supports human behavior and how it is affected by disease. In this study, we present results showing that cortical hubs and their associated cortical networks are largely confined to primary sensory and motor brain regions in the infant brain. Our findings in infants stand in stark contrast to the situation found in adults where the majority of cortical hubs and hub-related networks are located in heteromodal association cortex. Our findings suggest that the functional network architecture in infants is linked to support tasks that are of a perception-action nature.}, Author = {Fransson, Peter and Aden, Ulrika and Blennow, Mats and Lagercrantz, Hugo}, Date-Added = {2014-09-22 19:18:16 +0000}, Date-Modified = {2014-09-22 19:19:57 +0000}, Doi = {10.1093/cercor/bhq071}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {human; infant; Child; fMRI; default mode network; resting-state connectivity; network analysis; graph theory}, Mesh = {Adult; Aging; Brain Mapping; Brain Waves; Cerebral Cortex; Cohort Studies; Female; Humans; Infant; Magnetic Resonance Imaging; Male; Nerve Net; Neural Pathways; Neuropsychological Tests; Young Adult}, Month = {Jan}, Number = {1}, Pages = {145-54}, pmid = {20421249}, Pst = {ppublish}, Title = {The functional architecture of the infant brain as revealed by resting-state fMRI}, Volume = {21}, Year = {2011}, url = {papers/Fransson_CerebCortex2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhq071}} @article{Buckner:2009, Abstract = {Recent evidence suggests that some brain areas act as hubs interconnecting distinct, functionally specialized systems. These nexuses are intriguing because of their potential role in integration and also because they may augment metabolic cascades relevant to brain disease. To identify regions of high connectivity in the human cerebral cortex, we applied a computationally efficient approach to map the degree of intrinsic functional connectivity across the brain. Analysis of two separate functional magnetic resonance imaging datasets (each n = 24) demonstrated hubs throughout heteromodal areas of association cortex. Prominent hubs were located within posterior cingulate, lateral temporal, lateral parietal, and medial/lateral prefrontal cortices. Network analysis revealed that many, but not all, hubs were located within regions previously implicated as components of the default network. A third dataset (n = 12) demonstrated that the locations of hubs were present across passive and active task states, suggesting that they reflect a stable property of cortical network architecture. To obtain an accurate reference map, data were combined across 127 participants to yield a consensus estimate of cortical hubs. Using this consensus estimate, we explored whether the topography of hubs could explain the pattern of vulnerability in Alzheimer's disease (AD) because some models suggest that regions of high activity and metabolism accelerate pathology. Positron emission tomography amyloid imaging in AD (n = 10) compared with older controls (n = 29) showed high amyloid-beta deposition in the locations of cortical hubs consistent with the possibility that hubs, while acting as critical way stations for information processing, may also augment the underlying pathological cascade in AD.}, Author = {Buckner, Randy L and Sepulcre, Jorge and Talukdar, Tanveer and Krienen, Fenna M and Liu, Hesheng and Hedden, Trey and Andrews-Hanna, Jessica R and Sperling, Reisa A and Johnson, Keith A}, Date-Added = {2014-09-22 13:30:12 +0000}, Date-Modified = {2014-09-22 13:30:12 +0000}, Doi = {10.1523/JNEUROSCI.5062-08.2009}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Adolescent; Aged; Aged, 80 and over; Alzheimer Disease; Brain Mapping; Cerebral Cortex; Female; Humans; Male; Middle Aged; Nerve Net; Neural Pathways; Young Adult}, Month = {Feb}, Number = {6}, Pages = {1860-73}, Pmc = {PMC2750039}, pmid = {19211893}, Pst = {ppublish}, Title = {Cortical hubs revealed by intrinsic functional connectivity: mapping, assessment of stability, and relation to Alzheimer's disease}, Volume = {29}, Year = {2009}, url = {papers/Buckner_JNeurosci2009.pdf}, Bdsk-File-2 = {papers/Buckner_JNeurosci2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5062-08.2009}} @article{Fox:2007a, Abstract = {The majority of functional neuroscience studies have focused on the brain's response to a task or stimulus. However, the brain is very active even in the absence of explicit input or output. In this Article we review recent studies examining spontaneous fluctuations in the blood oxygen level dependent (BOLD) signal of functional magnetic resonance imaging as a potentially important and revealing manifestation of spontaneous neuronal activity. Although several challenges remain, these studies have provided insight into the intrinsic functional architecture of the brain, variability in behaviour and potential physiological correlates of neurological and psychiatric disease.}, Author = {Fox, Michael D and Raichle, Marcus E}, Date-Added = {2014-09-19 14:37:27 +0000}, Date-Modified = {2014-09-19 14:38:00 +0000}, Doi = {10.1038/nrn2201}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {resting-state fMRI; default mode network; functional connectivity;}, Mesh = {Animals; Brain; Brain Mapping; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Oxygen}, Month = {Sep}, Number = {9}, Pages = {700-11}, pmid = {17704812}, Pst = {ppublish}, Title = {Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging}, Volume = {8}, Year = {2007}, url = {papers/Fox_NatRevNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2201}} @article{Barch:2013, Abstract = {Understanding how brain systems interact to produce complex behaviors is a central goal of cognitive neuroscience. Palaniyappan and colleagues enhance our understanding of how interactions among brain systems contribute to individual differences in function and psychopathology by examining causal interactions among the salience and central executive systems in schizophrenia.}, Author = {Barch, Deanna M}, Date-Added = {2014-09-19 14:00:06 +0000}, Date-Modified = {2014-09-19 14:00:06 +0000}, Doi = {10.1016/j.tics.2013.09.004}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Mesh = {Brain; Brain Mapping; Female; Humans; Male; Neural Pathways; Schizophrenia}, Month = {Dec}, Number = {12}, Pages = {603-5}, Pmc = {PMC3858486}, pmid = {24080424}, Pst = {ppublish}, Title = {Brain network interactions in health and disease}, Volume = {17}, Year = {2013}, url = {papers/Barch_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.004}} @article{Uddin:2013, Abstract = {In recent work, O'Reilly and colleagues demonstrate relatively intact interhemispheric functional connectivity in a macaque brain in the absence of major commissural fibers. This work adds to a growing body of literature challenging the notion that structural and functional brain connectivity metrics are related in a straightforward manner.}, Author = {Uddin, Lucina Q}, Date-Added = {2014-09-19 14:00:03 +0000}, Date-Modified = {2014-09-19 14:00:03 +0000}, Doi = {10.1016/j.tics.2013.09.011}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Mesh = {Animals; Brain Mapping; Brain Waves; Connectome; Female; Macaca mulatta; Male}, Month = {Dec}, Number = {12}, Pages = {600-2}, Pmc = {PMC3858496}, pmid = {24094797}, Pst = {ppublish}, Title = {Complex relationships between structural and functional brain connectivity}, Volume = {17}, Year = {2013}, url = {papers/Uddin_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.011}} @article{Zanto:2013, Abstract = {A recent study shows that the fronto-parietal network (FPN), and subregions therein, alters its functional connectivity with nodes of other networks based on task goals. Moreover, FPN patterns of connectivity not only reflect engagement of specific tasks, but also serve as a code that can be transferred to facilitate learning novel tasks.}, Author = {Zanto, Theodore P and Gazzaley, Adam}, Date-Added = {2014-09-19 14:00:00 +0000}, Date-Modified = {2014-09-19 14:00:00 +0000}, Doi = {10.1016/j.tics.2013.10.001}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Mesh = {Adaptation, Physiological; Brain; Brain Mapping; Female; Humans; Male; Neural Pathways; Psychomotor Performance}, Month = {Dec}, Number = {12}, Pages = {602-3}, Pmc = {PMC3873155}, pmid = {24129332}, Pst = {ppublish}, Title = {Fronto-parietal network: flexible hub of cognitive control}, Volume = {17}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.10.001}} @article{Singer:2013, Abstract = {Recent discoveries on the organisation of the cortical connectome together with novel data on the dynamics of neuronal interactions require an extension of classical concepts on information processing in the cerebral cortex. These new insights justify considering the brain as a complex, self-organised system with nonlinear dynamics in which principles of distributed, parallel processing coexist with serial operations within highly interconnected networks. The observed dynamics suggest that cortical networks are capable of providing an extremely high-dimensional state space in which a large amount of evolutionary and ontogenetically acquired information can coexist and be accessible to rapid parallel search.}, Author = {Singer, Wolf}, Date-Added = {2014-09-19 13:59:57 +0000}, Date-Modified = {2014-09-19 13:59:57 +0000}, Doi = {10.1016/j.tics.2013.09.006}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {cerebral cortex; nonlinear dynamics; oscillations; reservoir computing; synchrony}, Mesh = {Cerebral Cortex; Computer Simulation; Humans; Models, Neurological; Nerve Net; Nonlinear Dynamics}, Month = {Dec}, Number = {12}, Pages = {616-26}, pmid = {24139950}, Pst = {ppublish}, Title = {Cortical dynamics revisited}, Volume = {17}, Year = {2013}, url = {papers/Singer_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.006}} @article{Harmelech:2013, Abstract = {When the brain is 'at rest', spatiotemporal activity patterns emerge spontaneously, that is, in the absence of an overt task. However, what these patterns reveal about cortical function remains elusive. In this article, we put forward the hypothesis that the correlation patterns among these spontaneous fluctuations (SPs) reflect the profile of individual a priori cognitive biases, coded as synaptic efficacies in cortical networks. Thus, SPs offer a new means for mapping personal traits in both neurotypical and atypical cases. Three sets of observations and related empirical evidence provide support for this hypothesis. First, SPs correspond to activation patterns that occur during typical task performance. Second, individual differences in SPs reflect individual biases and abnormalities. Finally, SPs can be actively remodeled in a long-term manner by focused and intense cortical training.}, Author = {Harmelech, Tal and Malach, Rafael}, Date-Added = {2014-09-19 13:59:53 +0000}, Date-Modified = {2014-09-19 13:59:53 +0000}, Doi = {10.1016/j.tics.2013.09.014}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {BOLD-fMRI; a priori biases; cortex; human; resting state; spontaneous activity}, Mesh = {Animals; Bias (Epidemiology); Brain Mapping; Cerebral Cortex; Cognition; Humans; Neuroimaging; Neurons; Rest}, Month = {Dec}, Number = {12}, Pages = {606-15}, pmid = {24182697}, Pst = {ppublish}, Title = {Neurocognitive biases and the patterns of spontaneous correlations in the human cortex}, Volume = {17}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.014}} @article{Menon:2013, Abstract = {The human brain undergoes protracted developmental changes during which it constructs functional networks that engender complex cognitive abilities. Understanding brain function ultimately depends on knowledge of how dynamic interactions between distributed brain regions mature with age to produce sophisticated cognitive systems. This review summarizes recent progress in our understanding of the ontogeny of functional brain networks. Here I describe how complementary methods for probing functional connectivity are providing unique insights into the emergence and maturation of distinct functional networks from childhood to adulthood. I highlight six emerging principles governing the development of large-scale functional networks and discuss how they inform cognitive and affective function in typically developing children and in children with neurodevelopmental disorders.}, Author = {Menon, Vinod}, Date-Added = {2014-09-19 13:59:51 +0000}, Date-Modified = {2014-09-19 13:59:51 +0000}, Doi = {10.1016/j.tics.2013.09.015}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Mesh = {Animals; Brain; Brain Mapping; Developmental Disabilities; Humans; Models, Neurological; Nerve Net; Neural Pathways}, Month = {Dec}, Number = {12}, Pages = {627-40}, pmid = {24183779}, Pst = {ppublish}, Title = {Developmental pathways to functional brain networks: emerging principles}, Volume = {17}, Year = {2013}, url = {papers/Menon_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.015}} @article{Buckner:2013, Abstract = {The human cerebral cortex is vastly expanded relative to other primates and disproportionately occupied by distributed association regions. Here we offer a hypothesis about how association networks evolved their prominence and came to possess circuit properties vital to human cognition. The rapid expansion of the cortical mantle may have untethered large portions of the cortex from strong constraints of molecular gradients and early activity cascades that lead to sensory hierarchies. What fill the gaps between these hierarchies are densely interconnected networks that widely span the cortex and mature late into development. Limitations of the tethering hypothesis are discussed as well as its broad implications for understanding critical features of the human brain as a byproduct of size scaling.}, Author = {Buckner, Randy L and Krienen, Fenna M}, Date-Added = {2014-09-19 13:59:47 +0000}, Date-Modified = {2014-09-19 13:59:47 +0000}, Doi = {10.1016/j.tics.2013.09.017}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {cerebellum; cortical circuits; default network; prefrontal cortex; prospection; social cognition}, Mesh = {Animals; Biological Evolution; Brain; Brain Mapping; Cognition; Humans; Neural Pathways}, Month = {Dec}, Number = {12}, Pages = {648-65}, pmid = {24210963}, Pst = {ppublish}, Title = {The evolution of distributed association networks in the human brain}, Volume = {17}, Year = {2013}, url = {papers/Buckner_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.017}} @article{Kim:2013, Abstract = {Mapping of neural connectivity across the mammalian brain is a daunting and exciting prospect. Current approaches can be divided into three classes: macroscale, focusing on coarse inter-regional connectivity; mesoscale, involving a finer focus on neurons and projections; and microscale, reconstructing full details of all synaptic contacts. It remains to be determined how to bridge the datasets or insights from the different levels of study. Here we review recent light-microscopy-based approaches that may help in integration across scales.}, Author = {Kim, Sung-Yon and Chung, Kwanghun and Deisseroth, Karl}, Date-Added = {2014-09-19 13:59:45 +0000}, Date-Modified = {2014-09-19 13:59:45 +0000}, Doi = {10.1016/j.tics.2013.10.005}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Mesh = {Animals; Brain; Brain Mapping; Humans; Microscopy; Neural Pathways}, Month = {Dec}, Number = {12}, Pages = {596-9}, pmid = {24210964}, Pst = {ppublish}, Title = {Light microscopy mapping of connections in the intact brain}, Volume = {17}, Year = {2013}, url = {papers/Kim_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.10.005}} @article{Rubinov:2013, Abstract = {Pathoconnectomics, the mapping of abnormal brain networks, is a popular current framework for the study of brain dysfunction in psychiatric disorders. In this review we evaluate the conceptual foundations of this framework, describe the construction and analysis of empirical models of brain networks or connectomes, and summarize recent reports of the large-scale whole-brain connectome organization of two candidate brain-network disorders, schizophrenia and autism. We consider the evidence for the abnormal brain-network nature of psychiatric disorders and find it inconclusive. For instance, although there is some evidence for more random whole-brain network organization in schizophrenia and autism, future studies need to determine if these and other observed brain-network abnormalities represent sufficient phenotypes of psychiatric disorders, in order to validate pathoconnectomics as a scientific and clinical framework.}, Author = {Rubinov, Mikail and Bullmore, Ed}, Date-Added = {2014-09-19 13:59:41 +0000}, Date-Modified = {2014-09-19 13:59:41 +0000}, Doi = {10.1016/j.tics.2013.10.007}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {MRI; complex networks; connectomics; endophenotype; psychiatry}, Mesh = {Brain; Humans; Mental Disorders; Microscopy; Nerve Net; Neural Pathways; Neuroimaging}, Month = {Dec}, Number = {12}, Pages = {641-7}, pmid = {24238779}, Pst = {ppublish}, Title = {Fledgling pathoconnectomics of psychiatric disorders}, Volume = {17}, Year = {2013}, url = {papers/Rubinov_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.10.007}} @article{Heuvel:2013, Abstract = {Virtually all domains of cognitive function require the integration of distributed neural activity. Network analysis of human brain connectivity has consistently identified sets of regions that are critically important for enabling efficient neuronal signaling and communication. The central embedding of these candidate 'brain hubs' in anatomical networks supports their diverse functional roles across a broad range of cognitive tasks and widespread dynamic coupling within and across functional networks. The high level of centrality of brain hubs also renders them points of vulnerability that are susceptible to disconnection and dysfunction in brain disorders. Combining data from numerous empirical and computational studies, network approaches strongly suggest that brain hubs play important roles in information integration underpinning numerous aspects of complex cognitive function.}, Author = {van den Heuvel, Martijn P and Sporns, Olaf}, Date-Added = {2014-09-19 12:27:08 +0000}, Date-Modified = {2014-09-19 12:31:02 +0000}, Doi = {10.1016/j.tics.2013.09.012}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {resting-state fMRI; connectivity; connectomics; default mode network; graph theory; review literature; Human; network analysis; network modelling; wholeBrain}, Mesh = {Brain; Cognition; Humans; Nerve Net; Neural Pathways}, Month = {Dec}, Number = {12}, Pages = {683-96}, pmid = {24231140}, Pst = {ppublish}, Title = {Network hubs in the human brain}, Volume = {17}, Year = {2013}, url = {papers/Heuvel_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.012}} @article{Brown:2001, Abstract = {'Independent component analysis' is a technique of data transformation that finds independent sources of activity in recorded mixtures of sources. It can be used to recover fluctuations of membrane potential from individual neurons in multiple-detector optical recordings. There are some examples in which more than 100 neurons can be separated simultaneously. Independent component analysis automatically separates overlapping action potentials, recovers action potentials of different sizes from the same neuron, removes artifacts and finds the position of each neuron on the detector array. One limitation is that the number of sources--neurons and artifacts--must be equal to or less than the number of simultaneous recordings. Independent component analysis also has many other applications in neuroscience including, removal of artifacts from EEG data, identification of spatially independent brain regions in fMRI recordings and determination of population codes in multi-unit recordings.}, Author = {Brown, G D and Yamada, S and Sejnowski, T J}, Date-Added = {2014-09-19 04:09:19 +0000}, Date-Modified = {2014-09-19 04:27:27 +0000}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {wholeBrain; Mathematics; Analysis of Variance; Methods; optical imaging}, Mesh = {Action Potentials; Algorithms; Animals; Brain; Electroencephalography; Humans; Linear Models; Membrane Potentials; Models, Neurological; Neurons}, Month = {Jan}, Number = {1}, Pages = {54-63}, pmid = {11163888}, Pst = {ppublish}, Title = {Independent component analysis at the neural cocktail party}, Volume = {24}, Year = {2001}, url = {papers/Brown_TrendsNeurosci2001.pdf}} @article{Liang:2011, Abstract = {Intrinsic connectional architecture of the brain is a crucial element in understanding the governing principle of brain organization. To date, enormous effort has been focused on addressing this issue in humans by combining resting-state functional magnetic resonance imaging (rsfMRI) with other techniques. However, this research area is significantly underexplored in animals, perhaps because of confounding effects of anesthetic agents used in most animal experiments on functional connectivity. To bridge this gap, we have systematically investigated the intrinsic connectional architecture in the rodent brain by using a previously established awake-animal imaging model. First, group independent component analysis was applied to the rsfMRI data to extract elementary functional clusters of the brain. The connectional relationships between these clusters, as evaluated by partial correlation analysis, were then used to construct a graph of whole-brain neural network. This network exhibited the typical features of small-worldness and strong community structures seen in the human brain. Finally, the whole-brain network was segregated into community structures using a graph-based analysis. The results of this work provided a functional atlas of intrinsic connectional architecture of the rat brain at both intraregion and interregion levels. More importantly, the current work revealed that functional networks in rats are organized in a nontrivial manner and conserve fundamental topological properties that are also seen in the human brain. Given the high psychopathological relevance of network organization of the brain, this study demonstrated the feasibility of studying mechanisms and therapies of multiple neurological and psychiatric diseases through translational research.}, Author = {Liang, Zhifeng and King, Jean and Zhang, Nanyin}, Date-Added = {2014-09-18 21:25:02 +0000}, Date-Modified = {2014-09-18 21:25:30 +0000}, Doi = {10.1523/JNEUROSCI.4557-10.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {resting-state fMRI; default mode network; rat; in vivo; functional connectivity; Motor Activity; awake}, Mesh = {Animals; Brain; Brain Mapping; Magnetic Resonance Imaging; Nerve Net; Neural Pathways; Neurons; Rats; Rats, Long-Evans}, Month = {Mar}, Number = {10}, Pages = {3776-83}, Pmc = {PMC3073070}, pmid = {21389232}, Pst = {ppublish}, Title = {Uncovering intrinsic connectional architecture of functional networks in awake rat brain}, Volume = {31}, Year = {2011}, url = {papers/Liang_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4557-10.2011}} @article{Hutchison:2010, Abstract = {The rodent brain is organized into functional networks that can be studied through examination of synchronized low-frequency spontaneous fluctuations (LFFs) of the functional magnetic resonance imaging -blood-oxygen-level-dependent (BOLD) signal. In this study, resting networks of LFFs were estimated from the whole-brain BOLD signals using independent component analysis (ICA). ICA provides a hypothesis-free technique for determining the functional connectivity map that does not require a priori selection of a seed region. Twenty Long-Evans rats were anesthetized with isoflurane (1%, n = 10) or ketamine/xylazine (50/6 mg . kg(-1) . h(-1) ip, n = 10) and imaged for 5-10 min in a 9.4 T MR scanner without experimental stimulation or task requirement. Independent, synchronous LFFs of BOLD signals were found to exist in clustered, bilaterally symmetric regions of both cortical and subcortical structures, including primary and secondary somatosensory cortices, motor cortices, visual cortices, posterior and anterior cingulate cortices, hippocampi, caudate-putamen, and thalamic and hypothalamic nuclei. The somatosensory and motor cortices typically demonstrated both symmetric and asymmetric components with unique frequency profiles. Similar independent network components were found under isoflurane and ketamine/xylazine anesthesia. The report demonstrates, for the first time, 12 independent resting networks that are bilaterally synchronous in different cortical and subcortical areas of the rat brain.}, Author = {Hutchison, R Matthew and Mirsattari, Seyed M and Jones, Craig K and Gati, Joseph S and Leung, L Stan}, Date-Added = {2014-09-18 21:06:38 +0000}, Date-Modified = {2014-09-18 21:08:30 +0000}, Doi = {10.1152/jn.00141.2010}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {resting-state fMRI; default mode network; rat; in vivo; functional connectivity}, Mesh = {Anesthesia; Animals; Brain; Brain Mapping; Functional Laterality; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Oxygen; Principal Component Analysis; Rats; Rats, Long-Evans; Rest}, Month = {Jun}, Number = {6}, Pages = {3398-406}, pmid = {20410359}, Pst = {ppublish}, Title = {Functional networks in the anesthetized rat brain revealed by independent component analysis of resting-state FMRI}, Volume = {103}, Year = {2010}, url = {papers/Hutchison_JNeurophysiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00141.2010}} @article{Lu:2007, Abstract = {Synchronized low-frequency spontaneous fluctuations of the functional MRI (fMRI) signal have recently been applied to investigate large-scale neuronal networks of the brain in the absence of specific task instructions. However, the underlying neural mechanisms of these fluctuations remain largely unknown. To this end, electrophysiological recordings and resting-state fMRI measurements were conducted in alpha-chloralose-anesthetized rats. Using a seed-voxel analysis strategy, region-specific, anesthetic dose-dependent fMRI resting-state functional connectivity was detected in bilateral primary somatosensory cortex (S1FL) of the resting brain. Cortical electroencephalographic signals were also recorded from bilateral S1FL; a visual cortex locus served as a control site. Results demonstrate that, unlike the evoked fMRI response that correlates with power changes in the gamma bands, the resting-state fMRI signal correlates with the power coherence in low-frequency bands, particularly the delta band. These data indicate that hemodynamic fMRI signal differentially registers specific electrical oscillatory frequency band activity, suggesting that fMRI may be able to distinguish the ongoing from the evoked activity of the brain.}, Author = {Lu, Hanbing and Zuo, Yantao and Gu, Hong and Waltz, James A and Zhan, Wang and Scholl, Clara A and Rea, William and Yang, Yihong and Stein, Elliot A}, Date-Added = {2014-09-18 21:03:49 +0000}, Date-Modified = {2014-09-18 21:04:47 +0000}, Doi = {10.1073/pnas.0705791104}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {resting-state fMRI; default mode network; rat; in vivo; Anesthesia; EEG; sleep; Delta Rhythm; wholeBrain}, Mesh = {Animals; Magnetic Resonance Imaging; Nerve Net; Rats}, Month = {Nov}, Number = {46}, Pages = {18265-9}, Pmc = {PMC2084331}, pmid = {17991778}, Pst = {ppublish}, Title = {Synchronized delta oscillations correlate with the resting-state functional MRI signal}, Volume = {104}, Year = {2007}, url = {papers/Lu_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0705791104}} @article{Nitz:2009, Abstract = {The registration of spatial information by neurons of the parietal cortex takes on many forms. In most experiments, spatially modulated parietal activity patterns are found to take as their frame of reference some part of the body such as the retina. However, recent findings obtained in single neuron recordings from both rat and monkey parietal cortex suggest that the frame of reference utilized by parietal cortex may also be abstract or arbitrary in nature. Evidence in rats comes from work indicating that parietal activity in freely behaving rodents is organized according to the space defined by routes taken through an environment. In monkeys, evidence for an object-centered frame of reference has recently been presented. The present work reviews single neuron recording experiments in parietal cortex of freely behaving rats and considers the potential contribution of parietal cortex in solving navigational tasks. It is proposed that parietal cortex, in interaction with the hippocampus, plays a critical role in the selection of the most appropriate route between two points and, in addition, produces a route-based positional signal capable of guiding sensorimotor transitions.}, Author = {Nitz, Douglas}, Date-Added = {2014-09-16 16:13:07 +0000}, Date-Modified = {2014-09-16 16:13:12 +0000}, Doi = {10.1016/j.nlm.2008.08.007}, Journal = {Neurobiol Learn Mem}, Journal-Full = {Neurobiology of learning and memory}, Keywords = {rat; Posterior parietal cortex; ppc; Spatial Behavior; navigation; Motor Activity; grid cells; Decision Making; goal directed behavior; retrosplenial cortex}, Mesh = {Action Potentials; Animals; Exploratory Behavior; Haplorhini; Hippocampus; Maze Learning; Memory; Motor Activity; Neurons; Parietal Lobe; Rats; Space Perception; Spatial Behavior}, Month = {Feb}, Number = {2}, Pages = {179-85}, pmid = {18804545}, Pst = {ppublish}, Title = {Parietal cortex, navigation, and the construction of arbitrary reference frames for spatial information}, Volume = {91}, Year = {2009}, url = {papers/Nitz_NeurobiolLearnMem2009.pdf}} @article{Calton:2009, Abstract = {The ability of an organism to accurately navigate from one place to another requires integration of multiple spatial constructs, including the determination of one's position and direction in space relative to allocentric landmarks, movement velocity, and the perceived location of the goal of the movement. In this review, we propose that while limbic areas are important for the sense of spatial orientation, the posterior parietal cortex is responsible for relating this sense with the location of a navigational goal and in formulating a plan to attain it. Hence, the posterior parietal cortex is important for the computation of the correct trajectory or route to be followed while navigating. Prefrontal and motor areas are subsequently responsible for executing the planned movement. Using this theory, we are able to bridge the gap between the rodent and primate literatures by suggesting that the allocentric role of the rodent PPC is largely analogous to the egocentric role typically emphasized in primates, that is, the integration of spatial orientation with potential goals in the planning of goal-directed movements.}, Author = {Calton, Jeffrey L and Taube, Jeffrey S}, Date-Added = {2014-09-16 15:16:53 +0000}, Date-Modified = {2014-09-16 15:21:15 +0000}, Doi = {10.1016/j.nlm.2008.09.015}, Journal = {Neurobiol Learn Mem}, Journal-Full = {Neurobiology of learning and memory}, Keywords = {rat; Posterior parietal cortex; ppc; Spatial Behavior; navigation; Motor Activity; grid cells; Decision Making; goal directed behavior; retrosplenial cortex}, Mesh = {Action Potentials; Animals; Cognition; Frontal Lobe; Goals; Hippocampus; Maze Learning; Neural Pathways; Neurons; Orientation; Parietal Lobe; Primates; Space Perception; Spatial Behavior}, Month = {Feb}, Number = {2}, Pages = {186-96}, Pmc = {PMC2666283}, pmid = {18929674}, Pst = {ppublish}, Title = {Where am I and how will I get there from here? A role for posterior parietal cortex in the integration of spatial information and route planning}, Volume = {91}, Year = {2009}, url = {papers/Calton_NeurobiolLearnMem2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.nlm.2008.09.015}} @article{Whitlock:2008, Abstract = {The navigational system of the mammalian cortex comprises a number of interacting brain regions. Grid cells in the medial entorhinal cortex and place cells in the hippocampus are thought to participate in the formation of a dynamic representation of the animal's current location, and these cells are presumably critical for storing the representation in memory. To traverse the environment, animals must be able to translate coordinate information from spatial maps in the entorhinal cortex and hippocampus into body-centered representations that can be used to direct locomotion. How this is done remains an enigma. We propose that the posterior parietal cortex is critical for this transformation.}, Author = {Whitlock, Jonathan R and Sutherland, Robert J and Witter, Menno P and Moser, May-Britt and Moser, Edvard I}, Date-Added = {2014-09-16 14:54:21 +0000}, Date-Modified = {2014-09-16 14:55:00 +0000}, Doi = {10.1073/pnas.0804216105}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Posterior parietal cortex; ppc; rat; grid cells; hippocampus; Spatial Behavior; navigation; Entorhinal Cortex;}, Mesh = {Animals; Behavior, Animal; Brain Mapping; Entorhinal Cortex; Hippocampus; Memory; Parietal Lobe; Rats; Spatial Behavior}, Month = {Sep}, Number = {39}, Pages = {14755-62}, Pmc = {PMC2567440}, pmid = {18812502}, Pst = {ppublish}, Title = {Navigating from hippocampus to parietal cortex}, Volume = {105}, Year = {2008}, url = {papers/Whitlock_ProcNatlAcadSciUSA2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0804216105}} @article{Nitz:2006, Abstract = {Quick and efficient traversal of learned routes is critical to the survival of many animals. Routes can be defined by both the ordering of navigational epochs, such as continued forward motion or execution of a turn, and the distances separating them. The neural substrates conferring the ability to fluidly traverse complex routes are not well understood, but likely entail interactions between frontal, parietal, and rhinal cortices and the hippocampus. This paper demonstrates that posterior parietal cortical neurons map both individual and multiple navigational epochs with respect to their order in a route. In direct contrast to spatial firing patterns of hippocampal neurons, parietal neurons discharged in a place- and direction-independent fashion. Parietal route maps were scalable and versatile in that they were independent of the size and spatial configuration of navigational epochs. The results provide a framework in which to consider parietal function in spatial cognition.}, Author = {Nitz, Douglas A}, Date-Added = {2014-09-16 14:51:10 +0000}, Date-Modified = {2014-09-16 14:51:44 +0000}, Doi = {10.1016/j.neuron.2006.01.037}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Posterior parietal cortex; ppc; rat; grid cells; hippocampus; Spatial Behavior; navigation; Entorhinal Cortex;}, Mesh = {Action Potentials; Animals; Behavior, Animal; Brain Mapping; Male; Maze Learning; Neurons; Parietal Lobe; Rats; Rats, Sprague-Dawley; Space Perception; Spatial Behavior; Speech Perception}, Month = {Mar}, Number = {5}, Pages = {747-56}, pmid = {16504949}, Pst = {ppublish}, Title = {Tracking route progression in the posterior parietal cortex}, Volume = {49}, Year = {2006}, url = {papers/Nitz_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.01.037}} @article{McNaughton:1994, Abstract = {Neural activity related to unrestrained movement through space was studied in rat sensorimotor and posterior parietal cortices during performance of an eight-arm, radial maze task. Nearly half of the cells exhibited movement-related activity that discriminated among three basic modes of locomotion: left turns, right turns, and forward motion. Correlates ranged from strong excitation (relative to the still condition) to strong inhibition, and were distributed among the movement modes in a variety of different ways. For example, cells that discriminated between clockwise and counterclockwise turns did so with either antagonistic responses or simple excitation or inhibition. Others showed either excitation or inhibition relative to both turning and the still condition, and hence were selective for forward motion. Many cells exhibited somatosensory responsiveness; however, in agreement with findings of others, motion correlates could rarely be sensibly explained by the somatosensory response. Moreover, movement correlates sometimes varied considerably with spatial context. Some cells exhibited more complex motion correlates, such as an apparent dependence on the nature of the preceding movement. Irrespective of the specific sensory or motor determinants of cell activity, which varied considerably among cells, the posterior neocortex of the rat appears to generate a robust and redundant internal representation of body motion through space. Such a representation could be useful in constructing "cognitive maps" of the environment.}, Author = {McNaughton, B L and Mizumori, S J and Barnes, C A and Leonard, B J and Marquis, M and Green, E J}, Date = {1994 Jan-Feb}, Date-Added = {2014-09-16 14:49:48 +0000}, Date-Modified = {2014-09-16 14:50:32 +0000}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {Posterior parietal cortex; ppc; rat; grid cells; hippocampus; Spatial Behavior; navigation; Entorhinal Cortex;}, Mesh = {Animals; Cerebral Cortex; Electrodes, Implanted; Electrophysiology; Male; Motor Cortex; Movement; Orientation; Rats; Rats, Inbred F344; Somatosensory Cortex; Space Perception}, Number = {1}, Pages = {27-39}, pmid = {8180489}, Pst = {ppublish}, Title = {Cortical representation of motion during unrestrained spatial navigation in the rat}, Volume = {4}, Year = {1994}} @article{Torrealba:2008, Abstract = {Spatial cognition is a complex higher function in mammals and is involved in a variety of tasks that can be explored in the laboratory. In this review we will discuss the role of the posterior parietal/anteromedial cortex of rodents, also known as the parietal association cortex, and the hippocampal formation in spatial navigation. We will also discuss other higher associational functions of the posterior parietal/anteromedial cortex as they relate to Dr. Pinto-Hamuy's contribution to understanding behavioral functions.}, Author = {Torrealba, Fernando and Vald{\'e}s, Jos{\'e} Luis}, Date-Added = {2014-09-15 15:48:41 +0000}, Date-Modified = {2014-09-15 15:56:33 +0000}, Doi = {/S0716-97602008000400002}, Journal = {Biol Res}, Journal-Full = {Biological research}, Keywords = {Posterior parietal cortex; ppc; connectivity; review literature; Spatial Behavior; navigation; grid cells; hippocampus; Neocortex; Association cortex; Motor Activity; Motor Cortex; Visual Cortex; Posterior Thalamic Nuclei; thalamus}, Mesh = {Animals; Cognition; Memory; Parietal Lobe; Rats; Space Perception; Spatial Behavior}, Number = {4}, Pages = {369-77}, pmid = {19621117}, Pst = {ppublish}, Title = {The parietal association cortex of the rat}, Volume = {41}, Year = {2008}, url = {papers/Torrealba_BiolRes2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/0716-97602008000400002}} @article{Massimini:2004, Abstract = {During much of sleep, virtually all cortical neurons undergo a slow oscillation (<1 Hz) in membrane potential, cycling from a hyperpolarized state of silence to a depolarized state of intense firing. This slow oscillation is the fundamental cellular phenomenon that organizes other sleep rhythms such as spindles and slow waves. Using high-density electroencephalogram recordings in humans, we show here that each cycle of the slow oscillation is a traveling wave. Each wave originates at a definite site and travels over the scalp at an estimated speed of 1.2-7.0 m/sec. Waves originate more frequently in prefrontal-orbitofrontal regions and propagate in an anteroposterior direction. Their rate of occurrence increases progressively reaching almost once per second as sleep deepens. The pattern of origin and propagation of sleep slow oscillations is reproducible across nights and subjects and provides a blueprint of cortical excitability and connectivity. The orderly propagation of correlated activity along connected pathways may play a role in spike timing-dependent synaptic plasticity during sleep.}, Author = {Massimini, Marcello and Huber, Reto and Ferrarelli, Fabio and Hill, Sean and Tononi, Giulio}, Date-Added = {2014-09-12 14:56:06 +0000}, Date-Modified = {2014-09-12 14:56:49 +0000}, Doi = {10.1523/JNEUROSCI.1318-04.2004}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Synapses;24 Pubmed search results 2008;Electroencephalography;research support, non-u.s. gov't;Adult;21 Neurophysiology;Neuronal Plasticity;Synaptic Transmission;Humans;Male;Cerebral Cortex;Membrane Potentials;Sleep}, Mesh = {Adult; Cerebral Cortex; Electroencephalography; Humans; Male; Membrane Potentials; Neuronal Plasticity; Sleep; Synapses; Synaptic Transmission}, Month = {Aug}, Number = {31}, Pages = {6862-70}, pmid = {15295020}, Pst = {ppublish}, Title = {The sleep slow oscillation as a traveling wave}, Volume = {24}, Year = {2004}, url = {papers/Massimini_JNeurosci2004.pdf}} @article{Hamburger:1963b, Author = {Hamburger, V}, Date-Added = {2014-09-11 20:30:27 +0000}, Date-Modified = {2014-09-11 20:30:27 +0000}, Doi = {10.1126/science.142.3597.1367}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Month = {Dec}, Number = {3597}, Pages = {1367}, pmid = {17752414}, Pst = {ppublish}, Title = {Embryology}, Volume = {142}, Year = {1963}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.142.3597.1367}} @article{Hamburger:1963a, Author = {Hamburger, V and Balaban, M}, Date-Added = {2014-09-11 20:30:24 +0000}, Date-Modified = {2016-01-13 18:16:29 +0000}, Journal = {Dev Biol}, Journal-Full = {Developmental biology}, Keywords = {EMBRYO; PERIODICITY; SPINAL CORD; Motor Activity; development}, Mesh = {Embryo, Nonmammalian; Periodicity; Spinal Cord}, Month = {Mar}, Pages = {533-45}, pmid = {13952299}, Pst = {ppublish}, Title = {Observations and experiments on spontaneous rhythmical behavior in the chick embryo}, Volume = {6}, Year = {1963}, url = {papers/HAMBURGER_DevBiol1963.pdf}} @article{Hamburger:1963, Author = {Hamburger, V}, Date-Added = {2014-09-11 20:30:22 +0000}, Date-Modified = {2016-01-13 18:16:04 +0000}, Journal = {Q Rev Biol}, Journal-Full = {The Quarterly review of biology}, Keywords = {BEHAVIOR, ANIMAL; BRAIN ELECTROPHYSIOLOGY; CHICK EMBRYO; ELECTROPHYSIOLOGY; EMBRYO; EXPERIMENTAL LAB STUDY; FISHES; MOVEMENT; NEURONS; PERIODICITY; PHYSIOLOGY, COMPARATIVE; REFLEX; SALAMANDERS; SPINAL CORD; Motor Activity; spontaneous activity; development}, Mesh = {Animals; Behavior, Animal; Brain; Chick Embryo; Electrophysiology; Embryo, Nonmammalian; Fishes; Movement; Neurons; Periodicity; Physiology, Comparative; Reflex; Research; Spinal Cord; Urodela}, Month = {Dec}, Pages = {342-65}, pmid = {14111168}, Pst = {ppublish}, Title = {SOME ASPECTS OF THE EMBRYOLOGY OF BEHAVIOR}, Volume = {38}, Year = {1963}, url = {papers/HAMBURGER_QRevBiol1963.pdf}} @article{Corner:1977, Author = {Corner, M A}, Date-Added = {2014-09-11 20:17:03 +0000}, Date-Modified = {2014-09-11 20:28:53 +0000}, Journal = {Prog Neurobiol}, Journal-Full = {Progress in neurobiology}, Keywords = {sleep; review literature; behavior; development; Embryo and Fetal Development; Mammals; Chick Embryo; Fishes/growth &development; Motor Activity; Spinal Cord}, Mesh = {Age Factors; Animals; Animals, Newborn; Anura; Brachyura; Chickens; Cockroaches; Fetus; Fishes; Lizards; Mollusca; Motor Activity; Muscle Contraction; Muscles; Phylogeny; Rats; Sheep; Sleep; Swimming; Wasps}, Number = {4}, Pages = {279-95}, pmid = {335440}, Pst = {ppublish}, Title = {Sleep and the beginnings of behavior in the animal kingdom--studies of ultradian motility cycles in early life}, Volume = {8}, Year = {1977}, url = {papers/Corner_ProgNeurobiol1977.pdf}} @article{Gramsbergen:1976, Abstract = {The development of the electroencephalogram (EEG) and, especially, behavioral state-specific EEG patterns was studied in white and black hooded rats of the Lister strain, aged 9-30 days. Movements of the rat were recorded and the behavioral state was monitored by means of a push-button device. The EEG was collected when the rat was in State 1 (regular respiration, absence of movements, and, after the 14th day when the rat eye opens, eyes closed), State 2 (irregular respiration, continual occurrence of twitches, and, after the 14th day, eyes closed), and in State 4 (irregular respiration, presence of gross body movements, and, after the 14th day, eyes opened). The EEG of rats on the 9th and 10th day did not reveal behavioral state-specific patterns. The amplitudes of the EEG were low and only low frequencies occurred. Between the 10th and 13th day an EEG pattern specific for State 1 containing high amplitudes developed. From the 14th day onwards spindles (frequencies from 14-18 Hz) occurred in the EEG during State 1. From the 14th day onwards, the EEG from the visual cortex during State 2 showed a regular and continually occurring 5-Hz rhythm. Bursts with 5-Hz waves were recorded from the visual cortex only intermittently during State 4. The EEG frequencies during the bursts varied between 5 and 7 Hz from the 17th day onwards. Computer analysis of the amplitude distributions showed a considerable increase in the power after the 10th day. The analysis of the frequency spectra indicated that the power increase occurs expecially in the higher frequencies of the EEG signal. Visual analysis as well as computer analysis of the EEG did not reveal systematic changes in the EEG after the 18th day when the EEG was similar to that recorded at older ages.}, Author = {Gramsbergen, A}, Date-Added = {2014-09-11 19:59:44 +0000}, Date-Modified = {2014-09-11 20:00:24 +0000}, Doi = {10.1002/dev.420090604}, Journal = {Dev Psychobiol}, Journal-Full = {Developmental psychobiology}, Keywords = {EEG; neurophysiology; rat; in vivo; Cerebral Cortex; sleep; development; spontaneous activity; cortical oscillations}, Mesh = {Age Factors; Animals; Behavior, Animal; Brain; Computers; Electroencephalography; Motor Activity; Motor Cortex; Rats; Respiration; Somatosensory Cortex; Visual Cortex}, Month = {Nov}, Number = {6}, Pages = {501-15}, pmid = {1001836}, Pst = {ppublish}, Title = {The development of the EEG in the rat}, Volume = {9}, Year = {1976}, url = {papers/Gramsbergen_DevPsychobiol1976.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dev.420090604}} @article{Connors:1984a, Abstract = {Epilepsy is characterized by highly synchronized paroxysmal bursts of activity within a large population of cortical neurones. Because such spontaneous, synchronized discharges can occur even in isolated blocks of neocortex, mechanisms for initiating and coordinating this activity must reside within the cortex itself. However, the specific cellular properties and local neural circuitry responsible for such behaviour are unknown. In a previous study of neocortex in vitro, we found that treatment with the convulsants penicillin and bicuculline led to synchronized bursts which were driven by unusually large and long-lasting excitatory synaptic conductances. I now report evidence that synchronized bursts are initiated by a small, spacially discrete subpopulation of cells located in the area comprising layer IV and upper layer V. Neural elements in these layers appear to project paroxysmal synaptic excitation radially, onto the neurones of other layers.}, Author = {Connors, B W}, Date = {1984 Aug 23-29}, Date-Added = {2014-09-11 19:33:37 +0000}, Date-Modified = {2014-09-11 19:34:41 +0000}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {epilepsy; seizure; GABA; in vitro; Neocortex; spontaneous activity; cortical oscillations}, Mesh = {Animals; Bicuculline; Cerebral Cortex; Electric Conductivity; Evoked Potentials; Glutamates; Glutamic Acid; Guinea Pigs; Kinetics; Neurons}, Number = {5979}, Pages = {685-7}, pmid = {6147755}, Pst = {ppublish}, Title = {Initiation of synchronized neuronal bursting in neocortex}, Volume = {310}, Year = {1984}, url = {papers/Connors_Nature1984.pdf}} @article{Woolf:1991, Author = {Woolf, N J}, Date-Added = {2014-09-11 19:10:19 +0000}, Date-Modified = {2014-09-11 19:12:36 +0000}, Journal = {Prog Neurobiol}, Journal-Full = {Progress in neurobiology}, Keywords = {sleep; review literature; Acetylcholine; cortical oscillations; spontaneous activity; Cerebral Cortex; thalamus; Brain Stem; midbrain}, Mesh = {Acetylcholine; Afferent Pathways; Animals; Arousal; Behavior; Brain; Brain Mapping; Choline O-Acetyltransferase; Cholinergic Fibers; Cognition; Efferent Pathways; Mammals; Motor Activity; Neurons; Rats; Sensation; Sleep; Spinal Cord}, Number = {6}, Pages = {475-524}, pmid = {1763188}, Pst = {ppublish}, Title = {Cholinergic systems in mammalian brain and spinal cord}, Volume = {37}, Year = {1991}, url = {papers/Woolf_ProgNeurobiol1991.pdf}} @article{Sanchez-Vives:2000a, Abstract = {Contrast adaptation is a psychophysical phenomenon, the neuronal bases of which reside largely in the primary visual cortex. The cellular mechanisms of contrast adaptation were investigated in the cat primary visual cortex in vivo through intracellular recording and current injections. Visual cortex cells, and to a much less extent, dorsal lateral geniculate nucleus (dLGN) neurons, exhibited a reduction in firing rate during prolonged presentations of a high-contrast visual stimulus, a process we termed high-contrast adaptation. In a majority of cortical and dLGN cells, the period of adaptation to high contrast was followed by a prolonged (5-80 sec) period of reduced responsiveness to a low-contrast stimulus (postadaptation suppression), an effect that was associated, and positively correlated, with a hyperpolarization of the membrane potential and an increase in apparent membrane conductance. In simple cells, the period of postadaptation suppression was not consistently associated with a decrease in the grating modulated component of the evoked synaptic barrages (the F1 component). The generation of the hyperpolarization appears to be at least partially intrinsic to the recorded cells, because the induction of neuronal activity with the intracellular injection of current resulted in both a hyperpolarization of the membrane potential and a decrease in the spike response to either current injections or visual stimuli. Conversely, high-contrast visual stimulation could suppress the response to low-intensity sinusoidal current injection. We conclude that control of the membrane potential by intrinsic neuronal mechanisms contributes importantly to the adaptation of neuronal responsiveness to varying levels of contrast. This feedback mechanism, internal to cortical neurons, provides them with the ability to continually adjust their responsiveness as a function of their history of synaptic and action potential activity.}, Author = {Sanchez-Vives, M V and Nowak, L G and McCormick, D A}, Date-Added = {2014-09-11 17:58:19 +0000}, Date-Modified = {2014-09-11 17:58:49 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {sleep; slow oscillations; Neocortex; cat; spontaneous activity; in vivo; Anesthesia}, Mesh = {Adaptation, Ocular; Animals; Cats; Contrast Sensitivity; Electric Stimulation; Electrophysiology; Evoked Potentials, Visual; Membrane Potentials; Neurons; Photic Stimulation; Potassium Channels; Signal Transduction; Visual Cortex}, Month = {Jun}, Number = {11}, Pages = {4267-85}, pmid = {10818163}, Pst = {ppublish}, Title = {Membrane mechanisms underlying contrast adaptation in cat area 17 in vivo}, Volume = {20}, Year = {2000}, url = {papers/Sanchez-Vives_JNeurosci2000.pdf}} @article{Krosigk:1993, Abstract = {Spindle waves are a prototypical example of synchronized oscillations, a common feature of neuronal activity in thalamic and cortical systems in sleeping and waking animals. Spontaneous spindle waves recorded from slices of the ferret lateral geniculate nucleus were generated by rebound burst firing in relay cells. This rebound burst firing resulted from inhibitory postsynaptic potentials arriving from the perigeniculate nucleus, the cells of which were activated by burst firing in relay neurons. Reduction of gamma-aminobutyric acidA (GABAA) receptor-mediated inhibition markedly enhanced GABAB inhibitory postsynaptic potentials in relay cells and subsequently generated a slowed and rhythmic population activity resembling that which occurs during an absence seizure. Pharmacological block of GABAB receptors abolished this seizure-like activity but not normal spindle waves, suggesting that GABAB antagonists may be useful in the treatment of absence seizures.}, Author = {von Krosigk, M and Bal, T and McCormick, D A}, Date-Added = {2014-09-11 14:29:58 +0000}, Date-Modified = {2014-09-11 14:29:58 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Animals; Baclofen; Bicuculline; Calcium; Epilepsy, Absence; Ferrets; Geniculate Bodies; Membrane Potentials; Neurons; Potassium; Receptors, Amino Acid; Receptors, GABA-A; Receptors, Glutamate; Receptors, Kainic Acid; Receptors, N-Methyl-D-Aspartate}, Month = {Jul}, Number = {5119}, Pages = {361-4}, pmid = {8392750}, Pst = {ppublish}, Title = {Cellular mechanisms of a synchronized oscillation in the thalamus}, Volume = {261}, Year = {1993}} @article{Steriade:1993d, Abstract = {Sleep is characterized by synchronized events in billions of synaptically coupled neurons in thalamocortical systems. The activation of a series of neuromodulatory transmitter systems during awakening blocks low-frequency oscillations, induces fast rhythms, and allows the brain to recover full responsiveness. Analysis of cortical and thalamic networks at many levels, from molecules to single neurons to large neuronal assemblies, with a variety of techniques, ranging from intracellular recordings in vivo and in vitro to computer simulations, is beginning to yield insights into the mechanisms of the generation, modulation, and function of brain oscillations.}, Author = {Steriade, M and McCormick, D A and Sejnowski, T J}, Date-Added = {2014-09-11 14:29:55 +0000}, Date-Modified = {2014-09-11 18:37:40 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Animals; Arousal; Cerebral Cortex; Electroencephalography; Sleep; Thalamus}, Month = {Oct}, Number = {5134}, Pages = {679-85}, pmid = {8235588}, Pst = {ppublish}, Title = {Thalamocortical oscillations in the sleeping and aroused brain}, Volume = {262}, Year = {1993}, url = {papers/Steriade_Science1993.pdf}} @article{Blumenfeld:2000, Abstract = {Absence seizures (3-4 Hz) and sleep spindles (6-14 Hz) occur mostly during slow-wave sleep and have been hypothesized to involve the same corticothalamic network. However, the mechanism by which this network transforms from one form of activity to the other is not well understood. Here we examine this question using ferret lateral geniculate nucleus slices and stimulation of the corticothalamic tract. A feedback circuit, meant to mimic the cortical influence in vivo, was arranged such that thalamic burst firing resulted in stimulation of the corticothalamic tract. Stimuli were either single shocks to mimic normal action potential firing by cortical neurons or high-frequency bursts (six shocks at 200 Hz) to simulate increased cortical firing, such as during seizures. With one corticothalamic stimulus per thalamic burst, 6-10 Hz oscillations resembling spindle waves were generated. However, if the stimulation was a burst, the network immediately transformed into a 3-4 Hz paroxysmal oscillation. This transition was associated with a strong increase in the burst firing of GABAergic perigeniculate neurons. In addition, thalamocortical neurons showed a transition from fast (100-150 msec) IPSPs to slow ( approximately 300 msec) IPSPs. The GABA(B) receptor antagonist CGP 35348 blocked the slow IPSPs and converted the 3-4 Hz paroxysmal oscillations back to 6-10 Hz spindle waves. Conversely, the GABA(A) receptor antagonist picrotoxin blocked spindle frequency oscillations resulting in 3-4 Hz oscillations with either single or burst stimuli. We suggest that differential activation of thalamic GABA(A) and GABA(B) receptors in response to varying corticothalamic input patterns may be critical in setting the oscillation frequency of thalamocortical network interactions.}, Author = {Blumenfeld, H and McCormick, D A}, Date-Added = {2014-09-11 14:28:46 +0000}, Date-Modified = {2014-09-11 14:28:46 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Cerebral Cortex; Electric Stimulation; Evoked Potentials; Female; Ferrets; GABA Antagonists; Geniculate Bodies; Male; Microelectrodes; Nerve Net; Neural Conduction; Neurons; Organophosphorus Compounds; Picrotoxin; Reaction Time; Thalamus; gamma-Aminobutyric Acid}, Month = {Jul}, Number = {13}, Pages = {5153-62}, pmid = {10864972}, Pst = {ppublish}, Title = {Corticothalamic inputs control the pattern of activity generated in thalamocortical networks}, Volume = {20}, Year = {2000}} @article{McCormick:2001, Abstract = {The highly interconnected networks of the mammalian forebrain can generate a wide variety of synchronized activities, including those underlying epileptic seizures, which often appear as a transformation of otherwise normal brain rhythms. The cerebral cortex and hippocampus are particularly prone to the generation of the large, synchronized bursts of activity underlying many forms of seizures owing to strong recurrent excitatory connections, the presence of intrinsically burst-generating neurons, ephaptic interactions among closely spaced neurons, and synaptic plasticity. The simplest form of epileptiform activity in these structures is the interictal spike, a synchronized burst of action potentials generated by recurrent excitation, followed by a period of hyperpolarization, in a localized pool of pyramidal neurons. Seizures can also be generated in response to a loss of balance between excitatory and inhibitory influences and can take the form of either tonic depolarizations or repetitive, rhythmic burst discharges, either as clonic or spike-wave activity, again mediated both by intrinsic membrane properties and synaptic interactions. The interaction of the cerebral cortex and the thalamus, in conjunction with intrathalamic communication, can also generate spike waves similar to those occurring during human absence seizure discharges. Although epileptic syndromes and their causes are diverse, the cellular mechanisms of seizure generation appear to fall into only two categories: rhythmic or tonic "runaway" excitation or the synchronized and rhythmic interplay between excitatory and inhibitory neurons and membrane conductances.}, Author = {McCormick, D A and Contreras, D}, Date-Added = {2014-09-11 14:28:36 +0000}, Date-Modified = {2014-09-11 14:28:36 +0000}, Doi = {10.1146/annurev.physiol.63.1.815}, Journal = {Annu Rev Physiol}, Journal-Full = {Annual review of physiology}, Mesh = {Animals; Brain; Electroencephalography; Epilepsy; Humans; Neural Pathways; Neurons}, Pages = {815-46}, pmid = {11181977}, Pst = {ppublish}, Title = {On the cellular and network bases of epileptic seizures}, Volume = {63}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.physiol.63.1.815}} @article{McCormick:2002, Abstract = {The cerebral cortex and thalamus can both generate cyclical oscillations of neuronal activity. Within the thalamus, sleep spindles are generated as a recurrent interaction between thalamocortical and thalamic reticular cells. Abnormally strong activation of the inhibitory thalamic reticular neurons can result in the transformation of this normal rhythm into one that resembles that underlying absence seizures. The cerebral cortex can generate periodic activity at < 1 Hz through recurrent excitation that is controlled by inhibition. Again, loss of inhibitory control allows this normal activity to become epileptiform. Together, the cerebral cortex and thalamus can form cyclical loops of activity that may contribute to some forms of epileptic seizures. It is proposed that hypsarrhythmic activity that is characteristic of children with infantile spasms may be generated through abnormal, locally synchronized bursts of activity within the cerebral cortex.}, Author = {McCormick, David A}, Date-Added = {2014-09-11 14:28:28 +0000}, Date-Modified = {2014-09-11 14:28:28 +0000}, Journal = {Int Rev Neurobiol}, Journal-Full = {International review of neurobiology}, Mesh = {Cerebral Cortex; Electroencephalography; Epilepsy, Absence; Humans; Oscillometry; Periodicity; Reference Values; Thalamus}, Pages = {99-114}, pmid = {12040908}, Pst = {ppublish}, Title = {Cortical and subcortical generators of normal and abnormal rhythmicity}, Volume = {49}, Year = {2002}} @article{Huguenard:2007, Abstract = {The circuitry within the thalamus creates an intrinsic oscillatory unit whose function depends critically on reciprocal synaptic connectivity between excitatory thalamocortical relay neurons and inhibitory thalamic reticular neurons along with a robust post-inhibitory rebound mechanism in relay neurons. Feedforward and feedback connections between cortex and thalamus reinforce the thalamic oscillatory activity into larger thalamocortical networks to generate sleep spindles and spike-wave discharge of generalized absence epilepsy. The degree of synchrony within the thalamic network seems to be crucial in determining whether normal (spindle) or pathological (spike-wave) oscillations occur, and recent studies show that regulation of excitability in the reticular nucleus leads to dynamical modulation of the state of the thalamic circuit and provide a basis for explaining how a variety of unrelated genetic alterations might lead to the spike-wave phenotype. In addition, given the central role of the reticular nucleus in generating spike-wave discharge, these studies have suggested specific interventions that would prevent seizures while still allowing normal spindle generation to occur. This review is part of the INMED/TINS special issue Physiogenic and pathogenic oscillations: the beauty and the beast, based on presentations at the annual INMED/TINS symposium (http://inmednet.com).}, Author = {Huguenard, John R and McCormick, David A}, Date-Added = {2014-09-11 14:27:32 +0000}, Date-Modified = {2014-09-11 14:27:32 +0000}, Doi = {10.1016/j.tins.2007.05.007}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Mesh = {Animals; Biological Clocks; Nonlinear Dynamics; Prosencephalon; Thalamus}, Month = {Jul}, Number = {7}, Pages = {350-6}, pmid = {17544519}, Pst = {ppublish}, Title = {Thalamic synchrony and dynamic regulation of global forebrain oscillations}, Volume = {30}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2007.05.007}} @article{Frohlich:2010, Abstract = {Local field potentials and the underlying endogenous electric fields (EFs) are traditionally considered to be epiphenomena of structured neuronal network activity. Recently, however, externally applied EFs have been shown to modulate pharmacologically evoked network activity in rodent hippocampus. In contrast, very little is known about the role of endogenous EFs during physiological activity states in neocortex. Here, we used the neocortical slow oscillation in vitro as a model system to show that weak sinusoidal and naturalistic EFs enhance and entrain physiological neocortical network activity with an amplitude threshold within the range of in vivo endogenous field strengths. Modulation of network activity by positive and negative feedback fields based on the network activity in real-time provide direct evidence for a feedback loop between neuronal activity and endogenous EF. This significant susceptibility of active networks to EFs that only cause small changes in membrane potential in individual neurons suggests that endogenous EFs could guide neocortical network activity.}, Author = {Fr{\"o}hlich, Flavio and McCormick, David A}, Date-Added = {2014-09-11 14:27:22 +0000}, Date-Modified = {2014-09-11 14:27:22 +0000}, Doi = {10.1016/j.neuron.2010.06.005}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Computer Simulation; Electric Stimulation; Evoked Potentials; Ferrets; Male; Models, Neurological; Neocortex; Nerve Net; Neurons; Nonlinear Dynamics; Oscillometry}, Month = {Jul}, Number = {1}, Pages = {129-43}, Pmc = {PMC3139922}, pmid = {20624597}, Pst = {ppublish}, Title = {Endogenous electric fields may guide neocortical network activity}, Volume = {67}, Year = {2010}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.06.005}} @article{Foust:2010, Abstract = {Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By using a recent improvement in voltage-sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission.}, Author = {Foust, Amanda and Popovic, Marko and Zecevic, Dejan and McCormick, David A}, Date-Added = {2014-09-11 14:27:18 +0000}, Date-Modified = {2014-09-11 14:27:18 +0000}, Doi = {10.1523/JNEUROSCI.0552-10.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Action Potentials; Animals; Axons; Biophysics; Cerebellum; Electric Stimulation; Green Fluorescent Proteins; Guanine Nucleotide Exchange Factors; Mice; Mice, Transgenic; Nerve Fibers; Neuropeptides; Patch-Clamp Techniques; Purkinje Cells; Voltage-Sensitive Dye Imaging; tau Proteins}, Month = {May}, Number = {20}, Pages = {6891-902}, Pmc = {PMC2990270}, pmid = {20484631}, Pst = {ppublish}, Title = {Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons}, Volume = {30}, Year = {2010}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0552-10.2010}} @article{Tahvildari:2012, Abstract = {The neocortex depends upon a relative balance of recurrent excitation and inhibition for its operation. During spontaneous Up states, cortical pyramidal cells receive proportional barrages of excitatory and inhibitory synaptic potentials. Many of these synaptic potentials arise from the activity of nearby neurons, although the identity of these cells is relatively unknown, especially for those underlying the generation of inhibitory synaptic events. To address these fundamental questions, we developed an in vitro submerged slice preparation of the mouse entorhinal cortex that generates robust and regular spontaneous recurrent network activity in the form of the slow oscillation. By performing whole-cell recordings from multiple cell types identified with green fluorescent protein expression and electrophysiological and/or morphological properties, we show that distinct functional subpopulations of neurons exist in the entorhinal cortex, with large variations in contribution to the generation of balanced excitation and inhibition during the slow oscillation. The most active neurons during the slow oscillation are excitatory pyramidal and inhibitory fast spiking interneurons, receiving robust barrages of both excitatory and inhibitory synaptic potentials. Weak action potential activity was observed in stellate excitatory neurons and somatostatin-containing interneurons. In contrast, interneurons containing neuropeptide Y, vasoactive intestinal peptide, or the 5-hydroxytryptamine (serotonin) 3a receptor, were silent. Our data demonstrate remarkable functional specificity in the interactions between different excitatory and inhibitory cortical neuronal subtypes, and suggest that it is the large recurrent interaction between pyramidal neurons and fast spiking interneurons that is responsible for the generation of persistent activity that characterizes the depolarized states of the cortex.}, Author = {Tahvildari, Babak and W{\"o}lfel, Markus and Duque, Alvaro and McCormick, David A}, Date-Added = {2014-09-11 14:26:46 +0000}, Date-Modified = {2014-09-11 14:26:46 +0000}, Doi = {10.1523/JNEUROSCI.1181-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Biological Clocks; Cerebral Cortex; Excitatory Postsynaptic Potentials; Female; Humans; Inhibitory Postsynaptic Potentials; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Inhibition; Neurons; Organ Culture Techniques; Reaction Time}, Month = {Aug}, Number = {35}, Pages = {12165-79}, Pmc = {PMC3466092}, pmid = {22933799}, Pst = {ppublish}, Title = {Selective functional interactions between excitatory and inhibitory cortical neurons and differential contribution to persistent activity of the slow oscillation}, Volume = {32}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1181-12.2012}} @article{Killackey:1995, Abstract = {The primary somatosensory cortex of small rodents is an isomorphic representation of the body surface. Similar representations are characteristic of the subcortical pathways, leading from the periphery to the cortex, and these representations develop in a sequence that begins at the periphery, and that ends in the cortex. Furthermore, central representations at all levels of the neural axis are altered by perinatal perturbations of the peripheral surface. This has led to the hypothesis that the periphery plays an instructional role in the formation of central neuronal structures. The morphology of this discrete organization has been examined thoroughly during the development of the thalamocortical projections. The mechanism(s) that underlies the formation of these representations remains unclear although some recent evidence suggests the involvement of activity-dependent processes that are modulated by 5-HT.}, Author = {Killackey, H P and Rhoades, R W and Bennett-Clarke, C A}, Date-Added = {2014-09-10 19:09:09 +0000}, Date-Modified = {2014-09-10 19:37:03 +0000}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {development; activity-dependent; spontaneous activity; Sensory Deprivation; barrels; Somatosensory Cortex; topographic map; Serotonin; rat}, Mesh = {Animals; Brain Mapping; Humans; Somatosensory Cortex}, Month = {Sep}, Number = {9}, Pages = {402-7}, pmid = {7482806}, Pst = {ppublish}, Title = {The formation of a cortical somatotopic map}, Volume = {18}, Year = {1995}, url = {papers/Killackey_TrendsNeurosci1995.pdf}} @article{Vertes:1984, Author = {Vertes, R P}, Date-Added = {2014-09-10 18:14:59 +0000}, Date-Modified = {2014-09-10 18:19:25 +0000}, Journal = {Prog Neurobiol}, Journal-Full = {Progress in neurobiology}, Keywords = {review literature; sleep; Spinal Cord; Brain Stem; Motor Activity; spontaneous activity}, Mesh = {Animals; Brain Mapping; Brain Stem; Cardiovascular Physiological Phenomena; Cats; Cortical Synchronization; Eye Movements; Geniculate Bodies; Hippocampus; Humans; Locus Coeruleus; Muscle Contraction; Muscle Tonus; Occipital Lobe; Pons; Rats; Respiration; Reticular Formation; Sleep, REM}, Number = {3}, Pages = {241-88}, pmid = {6382442}, Pst = {ppublish}, Title = {Brainstem control of the events of REM sleep}, Volume = {22}, Year = {1984}, url = {papers/Vertes_ProgNeurobiol1984.pdf}} @article{Jouvet-Mounier:1970, Author = {Jouvet-Mounier, D and Astic, L and Lacote, D}, Date-Added = {2014-09-10 15:19:30 +0000}, Date-Modified = {2014-09-10 15:20:36 +0000}, Doi = {10.1002/dev.420020407}, Journal = {Dev Psychobiol}, Journal-Full = {Developmental psychobiology}, Keywords = {sleep; rat; cat; Guinea Pigs; development; behavior; Motor Activity; spontaneous activity; state}, Mesh = {Age Factors; Animals; Animals, Newborn; Attention; Behavior, Animal; Cats; Circadian Rhythm; Electroencephalography; Guinea Pigs; Rats; Sleep; Sleep Stages; Wakefulness; Weaning}, Number = {4}, Pages = {216-39}, pmid = {5527153}, Pst = {ppublish}, Title = {Ontogenesis of the states of sleep in rat, cat, and guinea pig during the first postnatal month}, Volume = {2}, Year = {1970}, url = {papers/Jouvet-Mounier_DevPsychobiol1970.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dev.420020407}} @article{Stelzner:1975, Author = {Stelzner, D J and Ershler, W B and Weber, E D}, Date-Added = {2014-09-10 15:09:11 +0000}, Date-Modified = {2014-09-10 15:10:49 +0000}, Journal = {Exp Neurol}, Journal-Full = {Experimental neurology}, Keywords = {development; spontaneous activity; Spinal Cord; Brain; Cerebral Cortex; behavior; Motor Activity; rat;}, Mesh = {Acute Disease; Age Factors; Animals; Animals, Newborn; Chronic Disease; Female; Gliosis; Locomotion; Motor Skills; Neural Pathways; Posture; Rats; Red Nucleus; Reflex, Abnormal; Spinal Cord; Spinal Cord Injuries}, Month = {Jan}, Number = {1}, Pages = {156-77}, pmid = {1109335}, Pst = {ppublish}, Title = {Effects of spinal transection in neonatal and weanling rats: survival of function}, Volume = {46}, Year = {1975}, url = {papers/Stelzner_ExpNeurol1975.pdf}} @article{Altman:1975, Abstract = {In laboratory rats (Rattus norvegicus) aged 1 to 21 days emergence of postural and locomotor skills was studied in the open field and in experimental situations with homing used as motivation. Righting is mediated initially by curving and rocking of the trunk, later head and shoulder are rotated, and lastly the hindlimbs turn and provide co-ordinated support. Pivoting prodominates during the second half of the first week, crawling during most of the second week, and walking or running by the end of the second week. Balancing on narrow paths and compensating for lateral displacement on rotating rods mature later, as do various skills (climbing up or down on inclined surfaces, rods and ropes, and jumping across gaps) that require substantial hindlimb co-ordiantion.}, Author = {Altman, J and Sudarshan, K}, Date-Added = {2014-09-10 14:30:39 +0000}, Date-Modified = {2014-09-10 14:31:31 +0000}, Journal = {Anim Behav}, Journal-Full = {Animal behaviour}, Keywords = {development; Motor Activity; behavior; Locomotion; rat}, Mesh = {Animals; Animals, Newborn; Female; Forelimb; Head; Hindlimb; Housing, Animal; Locomotion; Male; Motor Skills; Movement; Orientation; Posture; Rats}, Month = {Nov}, Number = {4}, Pages = {896-920}, pmid = {1200422}, Pst = {ppublish}, Title = {Postnatal development of locomotion in the laboratory rat}, Volume = {23}, Year = {1975}, url = {papers/Altman_AnimBehav1975.pdf}} @article{Narayanan:1971, Author = {Narayanan, C H and Fox, M W and Hamburger, V}, Date-Added = {2014-09-09 02:31:40 +0000}, Date-Modified = {2014-09-10 14:57:16 +0000}, Journal = {Behaviour}, Journal-Full = {Behaviour}, Keywords = {development; rat; fetal; Embryo; spontaneous activity; Motor Activity; Spinal Cord; sleep; behavior}, Mesh = {Animals; Embryonic and Fetal Development; Female; Fetus; Motor Activity; Pregnancy; Pregnancy, Animal; Rats; Rats, Inbred Strains}, Number = {1}, Pages = {100-34}, pmid = {5157515}, Pst = {ppublish}, Title = {Prenatal development of spontaneous and evoked activity in the rat (Rattus norvegicus albinus)}, Volume = {40}, Year = {1971}, url = {papers/Narayanan_Behaviour1971.pdf}} @article{Blumberg:1994, Abstract = {Twitches of the limbs during REM sleep in adult mammals result from descending motor activation from the brainstem. In contrast, many spontaneous movements in embryos appear similar to REM-related twitches and result from the local firing of spinal motor neurons. To determine which mechanism produces twitches in neonates, we analyzed twitching in 5- and 8-day-old rat pups that had spinal cords transected in the lower thoracic region. This transection separated motor units controlling forelimb movements from motor units controlling hindlimb movements. Spinal transection did not significantly affect the amount of forelimb twitching. In contrast, the amount of hindlimb twitching in transected pups was reduced by only 35%-50%. Given that hindlimb twitching was not eliminated by spinal transection, it is concluded that there are 2 independent mechanisms producing twitches at these ages.}, Author = {Blumberg, M S and Lucas, D E}, Date-Added = {2014-09-08 20:28:18 +0000}, Date-Modified = {2014-09-08 20:28:45 +0000}, Journal = {Behav Neurosci}, Journal-Full = {Behavioral neuroscience}, Keywords = {Spinal Cord; Motor Activity; Motor Neurons; development; spontaneous activity; Movement; rat}, Mesh = {Animals; Animals, Newborn; Brain Stem; Female; Forelimb; Hindlimb; Male; Motor Activity; Motor Neurons; Neural Pathways; Rats; Sleep, REM; Spinal Cord}, Month = {Dec}, Number = {6}, Pages = {1196-202}, pmid = {7893412}, Pst = {ppublish}, Title = {Dual mechanisms of twitching during sleep in neonatal rats}, Volume = {108}, Year = {1994}, url = {papers/Blumberg_BehavNeurosci1994.pdf}} @article{Robinson:2000, Abstract = {Spontaneous motor activity (SMA) is a ubiquitous feature of fetal and infant behavior. Although SMA appears random, successive limb movements often occur in bouts. Bout organization was evident at all ages in fetal (embryonic day [E] 17-21) and infant (postnatal day [P] 1-9) rats, with nearly all bouts comprising 1-4 movements of different limbs. A computational model of SMA, including spontaneous activity of spinal motor neurons, intrasegmental and intersegmental interactions, recurrent inhibition, and descending influences, produced bouts with the same structure as that observed in perinatal rats. Consistent with the model, bouts were not eliminated on E20 after cervical spinal transection, suggesting that the brain is not necessary to produce bout organization. These investigations provide a foundation for understanding the contributions of SMA to neuromuscular and motor development.}, Author = {Robinson, S R and Blumberg, M S and Lane, M S and Kreber, L A}, Date-Added = {2014-09-08 20:24:42 +0000}, Date-Modified = {2014-09-08 20:24:56 +0000}, Journal = {Behav Neurosci}, Journal-Full = {Behavioral neuroscience}, Keywords = {Spinal Cord; Motor Activity; Motor Neurons; development; spontaneous activity; Movement; rat}, Mesh = {Animals; Animals, Newborn; Female; Fetal Movement; Male; Motor Activity; Motor Neurons; Neuromuscular Junction; Pregnancy; Rats; Rats, Sprague-Dawley; Spinal Cord}, Month = {Apr}, Number = {2}, Pages = {328-36}, pmid = {10832794}, Pst = {ppublish}, Title = {Spontaneous motor activity in fetal and infant rats is organized into discrete multilimb bouts}, Volume = {114}, Year = {2000}, url = {papers/Robinson_BehavNeurosci2000.pdf}} @article{Sokoloff:2000, Abstract = {In infant rats, huddling improves surface-to-volume ratios and provides metabolic savings during cold exposure. It is unclear, however, whether endothermy is also a necessary component of huddling. In the present experiment, huddles composed of infant Norway rats (2- or 8-day-olds), which produce heat endogenously, or Syrian golden hamsters (8-day-olds), which do not produce heat endogenously, were exposed to decreases in air temperature. Behavioral and physiological responses were monitored throughout the test. Rats, especially at 8 days of age, were better able to thermoregulate using huddling than hamsters, due in part to endogenous heat production. Furthermore, 8-day-old rats exhibited behavioral responses that promote heat retention, suggesting that both physiological and behavioral mechanisms contribute to effective thermoregulation during huddling in the cold.}, Author = {Sokoloff, G and Blumberg, M S and Adams, M M}, Date-Added = {2014-09-08 20:24:40 +0000}, Date-Modified = {2014-09-08 20:25:30 +0000}, Journal = {Behav Neurosci}, Journal-Full = {Behavioral neuroscience}, Keywords = {Thermodynamics; thermoregulation; development; spontaneous activity; Movement; rat}, Mesh = {Adipose Tissue, Brown; Animals; Animals, Newborn; Body Temperature Regulation; Cricetinae; Energy Metabolism; Mesocricetus; Oxygen Consumption; Rats; Social Environment; Vocalization, Animal}, Month = {Jun}, Number = {3}, Pages = {585-93}, pmid = {10883808}, Pst = {ppublish}, Title = {A comparative analysis of huddling in infant Norway rats and Syrian golden hamsters: does endothermy modulate behavior?}, Volume = {114}, Year = {2000}} @article{Schouenborg:2004, Abstract = {The study of plasticity in the central nervous system is a major and very dynamic neuroscience research field with enormous clinical potential. Considerable advances in this field have been made during the past 10 years. It now appears that most circuits in the brain and spinal cord show plasticity and that they can be modified by experience. Knowledge of the mechanisms of plasticity in the nervous system is therefore essential for the understanding of how the nervous system is wired during development and how it adapts in response to changes in the body and environment. Recent findings indicate that functional sensorimotor modules probe the sensory signals from the body that are generated as a consequence of module specific activity and use this sensory feedback to calibrate the strength in its input-output connections. This experience-dependent signal adapts the circuitry in the sensorimotor module to the body anatomy and biomechanics.}, Author = {Schouenborg, Jens}, Date-Added = {2014-09-08 20:21:33 +0000}, Date-Modified = {2014-09-08 20:22:21 +0000}, Doi = {10.1016/j.conb.2004.10.009}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Spinal Cord; Motor Activity; Motor Neurons; development; spontaneous activity; Movement}, Mesh = {Adaptation, Physiological; Animals; Central Nervous System; Feedback; Humans; Learning; Movement; Neural Pathways; Neuronal Plasticity; Sensation; Synaptic Transmission}, Month = {Dec}, Number = {6}, Pages = {693-7}, pmid = {15582370}, Pst = {ppublish}, Title = {Learning in sensorimotor circuits}, Volume = {14}, Year = {2004}, url = {papers/Schouenborg_CurrOpinNeurobiol2004.pdf}} @article{Varela:2001, Abstract = {The emergence of a unified cognitive moment relies on the coordination of scattered mosaics of functionally specialized brain regions. Here we review the mechanisms of large-scale integration that counterbalance the distributed anatomical and functional organization of brain activity to enable the emergence of coherent behaviour and cognition. Although the mechanisms involved in large-scale integration are still largely unknown, we argue that the most plausible candidate is the formation of dynamic links mediated by synchrony over multiple frequency bands.}, Author = {Varela, F and Lachaux, J P and Rodriguez, E and Martinerie, J}, Date-Added = {2014-09-03 13:17:07 +0000}, Date-Modified = {2014-09-03 13:18:55 +0000}, Doi = {10.1038/35067550}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {synchrony; review literature; neurophysiology; in vivo; EEG; LFP; Cerebral Cortex; Neocortex; technique; Methods; Theoretical; Computational Biology}, Mesh = {Animals; Attention; Brain; Cognition; Electrophysiology; Learning; Nerve Net}, Month = {Apr}, Number = {4}, Pages = {229-39}, pmid = {11283746}, Pst = {ppublish}, Title = {The brainweb: phase synchronization and large-scale integration}, Volume = {2}, Year = {2001}, url = {papers/Varela_NatRevNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35067550}} @article{Collins:2001, Abstract = {We have measured intracellular free calcium ([Ca(2+)]i) using Fura-2 or Ca(2+)-sensitive microelectrodes in voltage-clamped neurones of the snail, Helix aspersa. Caffeine-induced transient increases in [Ca(2+)]i were normally followed by a brief fall of [Ca(2+)]i below its pre-caffeine level. We investigated the cause of this undershoot by raising [Ca(2+)]i; and by inhibiting the plasma membrane or endoplasmic reticulum Ca ATPases (PMCA or SERCA respectively). When the cell membrane potential was decreased from -60 to -25mV, steady-state [Ca(2+)]i increased. The caffeine-induced transients were smaller while the undershoots were larger than in control conditions. When the PMCA was inhibited by high pH the steady-state [Ca(2+)]i increased by 100-400nM. The caffeine-induced [Ca(2+)]i increase and the subsequent undershoot both became larger. Injection of orthovanadate, which inhibits the PMCA and increases [Ca(2+)]i, did not block either effect of caffeine. But when the SERCA was inhibited by cyclopiazonic acid the undershoot disappeared. The phosphodiesterase inhibitor IBMX did not influence the undershoot. These results suggest that the undershoot is generated by the Ca(2+)] ATPase of the stores rather than that of the plasma membrane. Since the undershoot increased as [Ca(2+)]i increased, we conclude that at higher levels of [Ca(2+)]i the stores refill more rapidly.}, Author = {Collins, R O and Thomas, R C}, Date-Added = {2014-09-03 13:14:40 +0000}, Date-Modified = {2014-09-03 13:14:40 +0000}, Doi = {10.1054/ceca.2001.0209}, Journal = {Cell Calcium}, Journal-Full = {Cell calcium}, Mesh = {Animals; Caffeine; Calcium; Calcium-Transporting ATPases; Enzyme Inhibitors; Helix (Snails); Hydrogen-Ion Concentration; Indoles; Intracellular Fluid; Membrane Potentials; Neurons; Phosphodiesterase Inhibitors; Sarcoplasmic Reticulum}, Month = {Jul}, Number = {1}, Pages = {41-8}, pmid = {11396986}, Pst = {ppublish}, Title = {The effect of calcium pump inhibitors on the response of intracellular calcium to caffeine in snail neurones}, Volume = {30}, Year = {2001}, url = {papers/Collins_CellCalcium2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1054/ceca.2001.0209}} @article{Rolston:2009, Abstract = {Commercially available data acquisition systems for multielectrode recording from freely moving animals are expensive, often rely on proprietary software, and do not provide detailed, modifiable circuit schematics. When used in conjunction with electrical stimulation, they are prone to prolonged, saturating stimulation artifacts that prevent the recording of short-latency evoked responses. Yet electrical stimulation is integral to many experimental designs, and critical for emerging brain-computer interfacing and neuroprosthetic applications. To address these issues, we developed an easy-to-use, modifiable, and inexpensive system for multielectrode neural recording and stimulation. Setup costs are less than US{\$}10,000 for 64 channels, an order of magnitude lower than comparable commercial systems. Unlike commercial equipment, the system recovers rapidly from stimulation and allows short-latency action potentials (<1 ms post-stimulus) to be detected, facilitating closed-loop applications and exposing neural activity that would otherwise remain hidden. To illustrate this capability, evoked activity from microstimulation of the rodent hippocampus is presented. System noise levels are similar to existing platforms, and extracellular action potentials and local field potentials can be recorded simultaneously. The system is modular, in banks of 16 channels, and flexible in usage: while primarily designed for in vivo use, it can be combined with commercial preamplifiers to record from in vitro multielectrode arrays. The system's open-source control software, NeuroRighter, is implemented in C#, with an easy-to-use graphical interface. As C# functions in a managed code environment, which may impact performance, analysis was conducted to ensure comparable speed to C++ for this application. Hardware schematics, layout files, and software are freely available. Since maintaining wired headstage connections with freely moving animals is difficult, we describe a new method of electrode-headstage coupling using neodymium magnets.}, Author = {Rolston, John D and Gross, Robert E and Potter, Steve M}, Date-Added = {2014-09-03 13:13:44 +0000}, Date-Modified = {2014-09-03 13:13:44 +0000}, Doi = {10.3389/neuro.16.012.2009}, Journal = {Front Neuroeng}, Journal-Full = {Frontiers in neuroengineering}, Keywords = {data acquisition system; hippocampus; local field potential; microstimulation; multi-electrode array; population spike; recording; stimulation artifact}, Pages = {12}, Pmc = {PMC2722905}, pmid = {19668698}, Pst = {epublish}, Title = {A low-cost multielectrode system for data acquisition enabling real-time closed-loop processing with rapid recovery from stimulation artifacts}, Volume = {2}, Year = {2009}, url = {papers/Rolston_FrontNeuroeng2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.16.012.2009}} @article{Brickley:1998, Abstract = {Spatiotemporal correlations in the pattern of spontaneous and evoked retinal ganglion cell (RGC) activity are believed to influence the topographic organization of connections throughout the developing visual system. We have tested this hypothesis by examining the effects of interfering with these potential activity cues during development on the functional organization of binocular maps in the Xenopus frog optic tectum. Paired recordings combined with cross-correlation analyses demonstrated that exposing normal frogs to a continuous 1 Hz of stroboscopic illumination synchronized the firing of all three classes of RGC projecting to the tectum and induced similar patterns of temporally correlated activity across both lobes of the nucleus. Embryonic and eye-rotated larval animals were reared until early adulthood under equivalent stroboscopic conditions. The maps formed by each RGC class in the contralateral tectum showed normal topography and stratification after strobe rearing, but with consistently enlarged multiunit receptive fields. Maps of the ipsilateral eye, formed by crossed isthmotectal axons, showed significant disorder and misalignment with direct visual input from the retina, and in the eye-rotated animals complete compensatory reorientation of these maps usually induced by this procedure failed to occur. These findings suggest that refinement of retinal arbors in the tectum and the ability of crossed isthmotectal arbors to establish binocular convergence with these retinal afferents are disrupted when they all fire together. Our data thus provide direct experimental evidence that spatiotemporal activity patterns within and between the two eyes regulate the precision of their developing connections.}, Author = {Brickley, S G and Dawes, E A and Keating, M J and Grant, S}, Date-Added = {2014-09-03 13:09:34 +0000}, Date-Modified = {2014-09-03 13:12:12 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {activity manipulation; activity-development; development; Xenopus; visual system; optic tectum; neurophysiology; topographic map; ocular dominance; frog}, Mesh = {Aging; Animals; Brain Mapping; Electrophysiology; Embryo, Nonmammalian; Larva; Neuronal Plasticity; Ocular Physiological Phenomena; Photic Stimulation; Retina; Retinal Ganglion Cells; Rotation; Superior Colliculi; Time Factors; Vision, Binocular; Xenopus}, Month = {Feb}, Number = {4}, Pages = {1491-504}, pmid = {9454857}, Pst = {ppublish}, Title = {Synchronizing retinal activity in both eyes disrupts binocular map development in the optic tectum}, Volume = {18}, Year = {1998}, url = {papers/Brickley_JNeurosci1998.pdf}} @article{Leinekugel:1997, Abstract = {We asked whether GABA(A) and NMDA receptors may act in synergy in neonatal hippocampal slices, at a time when GABA exerts a depolarizing action. The GABA(A) receptor agonist isoguvacine reduced the voltage-dependent Mg2+ block of single NMDA channels recorded in cell-attached configuration from P(2-5) CA3 pyramidal neurons and potentiated the Ca2+ influx through NMDA channels. The synaptic response evoked by electrical stimulation of stratum radiatum was mediated by a synergistic interaction between GABA(A) and NMDA receptors. Network-driven Giant Depolarizing Potentials, which are a typical feature of the neonatal hippocampal network, provided coactivation of GABA(A) and NMDA receptors and were associated with spontaneous and synchronous Ca2+ increases in CA3 pyramidal neurons. Thus, at the early stages of development, GABA is a major excitatory transmitter that acts in synergy with NMDA receptors. This provides in neonatal neurons a hebbian stimulation that may be involved in neuronal plasticity and network formation in the developing hippocampus.}, Author = {Leinekugel, X and Medina, I and Khalilov, I and Ben-Ari, Y and Khazipov, R}, Date-Added = {2014-09-03 13:07:24 +0000}, Date-Modified = {2014-09-03 13:08:40 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {activity-dependent; development; hippocampus; rat; in vitro; GABA}, Mesh = {Action Potentials; Animals; Animals, Newborn; Calcium; Calcium Channels; GABA-A Receptor Agonists; Hippocampus; Ion Channel Gating; Isonicotinic Acids; Magnesium; Male; Membrane Potentials; Neuronal Plasticity; Rats; Rats, Wistar; Receptors, GABA-A; Receptors, N-Methyl-D-Aspartate; Synapses}, Month = {Feb}, Number = {2}, Pages = {243-55}, pmid = {9052795}, Pst = {ppublish}, Title = {Ca2+ oscillations mediated by the synergistic excitatory actions of GABA(A) and NMDA receptors in the neonatal hippocampus}, Volume = {18}, Year = {1997}, url = {papers/Leinekugel_Neuron1997.pdf}} @article{Akerman:2006a, Abstract = {Neurotransmission during development regulates synaptic maturation in neural circuits, but the contribution of different neurotransmitter systems is unclear. We investigated the role of GABAA receptor-mediated Cl- conductances in the development of synaptic responses in the Xenopus visual system. Intracellular Cl- concentration ([Cl-]i) was found to be high in immature tectal neurons and then falls over a period of several weeks. GABAergic synapses are present at early stages of tectal development and, when activated by optic nerve stimulation or visual stimuli, induce sustained depolarizing Cl- conductances that facilitate retinotectal transmission by NMDA receptors. To test whether depolarizing GABAergic inputs cooperate with NMDA receptors during activity-dependent maturation of glutamatergic synapses, we prematurely reduced [Cl-]i in tectal neurons in vivo by expressing the Cl- transporter KCC2. This blocked the normal developmental increase in AMPA receptor-mediated retinotectal transmission and increased GABAergic synaptic input to tectal neurons. Therefore, depolarizing GABAergic transmission plays a pivotal role in the maturation of excitatory transmission and controls the balance of excitation and inhibition in the developing retinotectal circuit.}, Author = {Akerman, Colin J and Cline, Hollis T}, Date-Added = {2014-09-03 13:04:33 +0000}, Date-Modified = {2014-09-03 13:05:52 +0000}, Doi = {10.1523/JNEUROSCI.0319-06.2006}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Chloride Channels; GABA; development; Xenopus; frog; in vivo; activity-dependent}, Mesh = {Animals; Cell Membrane; Chloride Channels; Electric Conductivity; Excitatory Postsynaptic Potentials; Larva; Membrane Potentials; Neural Inhibition; Synaptic Transmission; Visual Pathways; Xenopus laevis; gamma-Aminobutyric Acid}, Month = {May}, Number = {19}, Pages = {5117-30}, pmid = {16687503}, Pst = {ppublish}, Title = {Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo}, Volume = {26}, Year = {2006}, url = {papers/Akerman_JNeurosci2006a.pdf}} @article{Munz:2014, Abstract = {We examined how correlated firing controls axon remodeling, using in vivo time-lapse imaging and electrophysiological analysis of individual retinal ganglion cell (RGC) axons that were visually stimulated either synchronously or asynchronously relative to neighboring inputs in the Xenopus laevis optic tectum. RGCs stimulated out of synchrony rapidly lost the ability to drive tectal postsynaptic partners while their axons grew and added many new branches. In contrast, synchronously activated RGCs produced fewer new branches, but these were more stable. The effects of synchronous activation were prevented by the inhibition of neurotransmitter release and N-methyl-D-aspartate receptor (NMDAR) blockade, which is consistent with a role for synaptic NMDAR activation in the stabilization of axonal branches and suppression of further exploratory branch addition.}, Author = {Munz, Martin and Gobert, Delphine and Schohl, Anne and Poqu{\'e}russe, Jessie and Podgorski, Kaspar and Spratt, Perry and Ruthazer, Edward S}, Date-Added = {2014-09-02 15:39:41 +0000}, Date-Modified = {2014-09-02 15:40:21 +0000}, Doi = {10.1126/science.1251593}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {activity-dependent; Xenopus; frog; hebbian; development; optic tectum; visual system}, Mesh = {Animals; Axons; Electrical Synapses; Neuronal Plasticity; Photic Stimulation; Psychological Theory; Receptors, N-Methyl-D-Aspartate; Retinal Ganglion Cells; Superior Colliculi; Synaptic Transmission; Time-Lapse Imaging; Xenopus laevis}, Month = {May}, Number = {6186}, Pages = {904-9}, pmid = {24855269}, Pst = {ppublish}, Title = {Rapid Hebbian axonal remodeling mediated by visual stimulation}, Volume = {344}, Year = {2014}, url = {papers/Munz_Science2014.pdf}} @article{Schwartz:2001, Abstract = {The population of neurons participating in an epileptiform event varies from moment to moment. Most techniques currently used to localize epileptiform events in vivo have spatial and/or temporal sampling limitations. Here we show in an animal model that optical imaging based on intrinsic signals is an excellent method for in vivo mapping of clinically relevant epileptiform events, such as interictal spikes, ictal onsets, ictal spread and secondary homotopic foci. In addition, a decrease in the optical signal correlates spatially with a decrease in neuronal activity recorded from cortex surrounding an epileptic focus. Optical mapping of epilepsy might be a useful adjunct in the surgical treatment of neocortical epilepsy, which critically depends on the precise localization of intrinsically epileptogenic neurons.}, Author = {Schwartz, T H and Bonhoeffer, T}, Date-Added = {2014-08-29 18:48:38 +0000}, Date-Modified = {2014-08-29 18:49:24 +0000}, Doi = {10.1038/nm0901-1063}, Journal = {Nat Med}, Journal-Full = {Nature medicine}, Keywords = {optical physiology; optical imaging; intrinsic signal; in vivo; ferret; epilepsy; seizure; wholeBrain}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Electrophysiology; Epilepsies, Partial; Ferrets; Optics and Photonics}, Month = {Sep}, Number = {9}, Pages = {1063-7}, pmid = {11533712}, Pst = {ppublish}, Title = {In vivo optical mapping of epileptic foci and surround inhibition in ferret cerebral cortex}, Volume = {7}, Year = {2001}, url = {papers/Schwartz_NatMed2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm0901-1063}} @article{Suarez:2014, Abstract = {Bilateral integration of sensory and associative brain processing is achieved by precise connections between homologous regions in the two hemispheres via the corpus callosum. These connections form postnatally, and unilateral deprivation of sensory or spontaneous cortical activity during a critical period severely disrupts callosal wiring. However, little is known about how this early activity affects precise circuit formation. Here, using in utero electroporation of reporter genes, optogenetic constructs, and direct disruption of activity in callosal neurons combined with whisker ablations, we show that balanced interhemispheric activity, and not simply intact cortical activity in either hemisphere, is required for functional callosal targeting. Moreover, bilateral ablation of whiskers in symmetric or asymmetric configurations shows that spatially symmetric interhemispheric activity is required for appropriate callosal targeting. Our findings reveal a principle governing axon targeting, where spatially balanced activity between regions is required to establish their appropriate connectivity.}, Author = {Su{\'a}rez, Rodrigo and Fenlon, Laura R and Marek, Roger and Avitan, Lilach and Sah, Pankaj and Goodhill, Geoffrey J and Richards, Linda J}, Date-Added = {2014-08-29 18:12:23 +0000}, Date-Modified = {2014-08-29 18:42:02 +0000}, Doi = {10.1016/j.neuron.2014.04.040}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Corpus Callosum; Neocortex; Cerebral Cortex; development; activity-development; mirror symmetry; wholeBrain}, Mesh = {Action Potentials; Animals; Animals, Newborn; Corpus Callosum; Female; Functional Laterality; Mice; Neural Pathways; Pregnancy}, Month = {Jun}, Number = {6}, Pages = {1289-98}, pmid = {24945772}, Pst = {ppublish}, Title = {Balanced interhemispheric cortical activity is required for correct targeting of the corpus callosum}, Volume = {82}, Year = {2014}, url = {papers/Suárez_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.04.040}} @article{Brandes:2001, Author = {Ulrik Brandes}, Date-Added = {2014-08-27 21:06:11 +0000}, Date-Modified = {2014-08-27 21:07:09 +0000}, Journal = {Journal of Mathematical Sociology}, Keywords = {network analysis; graph theory; Mathematics; Theoretical; Computational Biology}, Pages = {163--177}, Title = {A Faster Algorithm for Betweenness Centrality}, Volume = {25}, Year = {2001}, url = {papers/Brandes_JournalofMathematicalSociology2001.pdf}} @article{Sporns:2005, Abstract = {The connection matrix of the human brain (the human "connectome") represents an indispensable foundation for basic and applied neurobiological research. However, the network of anatomical connections linking the neuronal elements of the human brain is still largely unknown. While some databases or collations of large-scale anatomical connection patterns exist for other mammalian species, there is currently no connection matrix of the human brain, nor is there a coordinated research effort to collect, archive, and disseminate this important information. We propose a research strategy to achieve this goal, and discuss its potential impact.}, Author = {Sporns, Olaf and Tononi, Giulio and K{\"o}tter, Rolf}, Date-Added = {2014-08-27 20:55:40 +0000}, Date-Modified = {2014-08-27 20:58:44 +0000}, Doi = {10.1371/journal.pcbi.0010042}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {connectivity; connectome; connectomics; network analysis; graph theory; Human; wholeBrain}, Mesh = {Animals; Brain; Humans; Nerve Net; Neurons; Synapses}, Month = {Sep}, Number = {4}, Pages = {e42}, Pmc = {PMC1239902}, pmid = {16201007}, Pst = {ppublish}, Title = {The human connectome: A structural description of the human brain}, Volume = {1}, Year = {2005}, url = {papers/Sporns_PLoSComputBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.0010042}} @article{Smith:2013, Abstract = {Spontaneous fluctuations in activity in different parts of the brain can be used to study functional brain networks. We review the use of resting-state functional MRI (rfMRI) for the purpose of mapping the macroscopic functional connectome. After describing MRI acquisition and image-processing methods commonly used to generate data in a form amenable to connectomics network analysis, we discuss different approaches for estimating network structure from that data. Finally, we describe new possibilities resulting from the high-quality rfMRI data being generated by the Human Connectome Project and highlight some upcoming challenges in functional connectomics.}, Author = {Smith, Stephen M and Vidaurre, Diego and Beckmann, Christian F and Glasser, Matthew F and Jenkinson, Mark and Miller, Karla L and Nichols, Thomas E and Robinson, Emma C and Salimi-Khorshidi, Gholamreza and Woolrich, Mark W and Barch, Deanna M and U{\u g}urbil, Kamil and Van Essen, David C}, Date-Added = {2014-08-27 20:40:21 +0000}, Date-Modified = {2014-08-27 20:41:34 +0000}, Doi = {10.1016/j.tics.2013.09.016}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {connectomics; network modelling; resting-state fMRI; human; default mode network; wholeBrain}, Mesh = {Animals; Brain; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Nerve Net; Neural Pathways; Oxygen; Rest}, Month = {Dec}, Number = {12}, Pages = {666-82}, Pmc = {PMC4004765}, pmid = {24238796}, Pst = {ppublish}, Title = {Functional connectomics from resting-state fMRI}, Volume = {17}, Year = {2013}, url = {papers/Smith_TrendsCognSci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2013.09.016}} @article{Nadel:1990, Author = {Nadel, L}, Date-Added = {2014-08-27 16:13:14 +0000}, Date-Modified = {2014-08-27 17:50:41 +0000}, Journal = {Ann N Y Acad Sci}, Journal-Full = {Annals of the New York Academy of Sciences}, Keywords = {goal directed behavior; rat; rodent; learning; memory; development; behavior; Locomotion; Motor Activity}, Mesh = {Animals; Cognition; Cues; Exploratory Behavior; Female; Hippocampus; Humans; Male; Models, Neurological; Neuronal Plasticity; Orientation; Rats; Spatial Behavior}, Pages = {613-26; discussion 626-36}, pmid = {2075964}, Pst = {ppublish}, Title = {Varieties of spatial cognition. Psychobiological considerations}, Volume = {608}, Year = {1990}, url = {papers/Nadel_AnnNYAcadSci1990.pdf}} @article{Zhang:2014, Abstract = {Top-down modulation of sensory processing allows the animal to select inputs most relevant to current tasks. We found that the cingulate (Cg) region of the mouse frontal cortex powerfully influences sensory processing in the primary visual cortex (V1) through long-range projections that activate local γ-aminobutyric acid-ergic (GABAergic) circuits. Optogenetic activation of Cg neurons enhanced V1 neuron responses and improved visual discrimination. Focal activation of Cg axons in V1 caused a response increase at the activation site but a decrease at nearby locations (center-surround modulation). Whereas somatostatin-positive GABAergic interneurons contributed preferentially to surround suppression, vasoactive intestinal peptide-positive interneurons were crucial for center facilitation. Long-range corticocortical projections thus act through local microcircuits to exert spatially specific top-down modulation of sensory processing.}, Author = {Zhang, Siyu and Xu, Min and Kamigaki, Tsukasa and Hoang Do, Johnny Phong and Chang, Wei-Cheng and Jenvay, Sean and Miyamichi, Kazunari and Luo, Liqun and Dan, Yang}, Date-Added = {2014-08-27 15:52:21 +0000}, Date-Modified = {2014-08-27 15:52:21 +0000}, Doi = {10.1126/science.1254126}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Animals; Animals, Genetically Modified; Discrimination (Psychology); GABAergic Neurons; Gyrus Cinguli; Interneurons; Mice; Mice, Inbred C57BL; Neural Inhibition; Photic Stimulation; Somatostatin; Visual Cortex; Visual Perception}, Month = {Aug}, Number = {6197}, Pages = {660-5}, pmid = {25104383}, Pst = {ppublish}, Title = {Selective attention. Long-range and local circuits for top-down modulation of visual cortex processing}, Volume = {345}, Year = {2014}, url = {papers/Zhang_Science2014.pdf}} @article{An:2014, Abstract = {Self-generated neuronal activity originating from subcortical regions drives early spontaneous motor activity, which is a hallmark of the developing sensorimotor system. However, the neural activity patterns and role of primary motor cortex (M1) in these early movements are still unknown. Combining voltage-sensitive dye imaging (VSDI) with simultaneous extracellular multielectrode recordings in postnatal day 3 (P3)-P5 rat primary somatosensory cortex (S1) and M1 in vivo, we observed that tactile forepaw stimulation induced spindle bursts in S1 and gamma and spindle bursts in M1. Approximately 40% of the spontaneous gamma and spindle bursts in M1 were driven by early motor activity, whereas 23.7% of the M1 bursts triggered forepaw movements. Approximately 35% of the M1 bursts were uncorrelated to movements and these bursts had significantly fewer spikes and shorter burst duration. Focal electrical stimulation of layer V neurons in M1 mimicking physiologically relevant 40 Hz gamma or 10 Hz spindle burst activity reliably elicited forepaw movements. We conclude that M1 is already involved in somatosensory information processing during early development. M1 is mainly activated by tactile stimuli triggered by preceding spontaneous movements, which reach M1 via S1. Only a fraction of M1 activity transients trigger motor responses directly. We suggest that both spontaneously occurring and sensory-evoked gamma and spindle bursts in M1 contribute to the maturation of corticospinal and sensorimotor networks required for the refinement of sensorimotor coordination.}, Author = {An, Shuming and Kilb, Werner and Luhmann, Heiko J}, Date-Added = {2014-08-20 19:13:39 +0000}, Date-Modified = {2014-08-20 19:14:01 +0000}, Doi = {10.1523/JNEUROSCI.4539-13.2014}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; in vivo; motor; neocortex; rat; somatosensory; wholeBrain}, Month = {Aug}, Number = {33}, Pages = {10870-83}, pmid = {25122889}, Pst = {ppublish}, Title = {Sensory-evoked and spontaneous gamma and spindle bursts in neonatal rat motor cortex}, Volume = {34}, Year = {2014}, url = {papers/An_JNeurosci2014.pdf}} @article{Spitzer:2012, Abstract = {For many years it has been assumed that the identity of the transmitters expressed by neurons is stable and unchanging. Recent work, however, shows that electrical activity can respecify neurotransmitter expression during development and in the mature nervous system, and an understanding is emerging of the molecular mechanisms underlying activity-dependent transmitter respecification. Changes in postsynaptic neurotransmitter receptor expression accompany and match changes in transmitter specification, thus enabling synaptic transmission. The functional roles of neurotransmitter respecification are beginning to be understood and appear to involve homeostatic synaptic regulation, which in turn influences behaviour. Activation of this novel form of plasticity by sensorimotor stimuli may provide clinical benefits.}, Author = {Spitzer, Nicholas C}, Date-Added = {2014-08-20 18:41:44 +0000}, Date-Modified = {2014-08-20 18:42:35 +0000}, Doi = {10.1038/nrn3154}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {review literature; Spontaneous activity; development; Neurotransmitters/*physiology; wholeBrain}, Mesh = {Animals; Calcium Signaling; Cell Differentiation; Cell Movement; Homeostasis; Models, Biological; Motor Activity; Neurons; Neurotransmitter Agents; Receptors, Neurotransmitter; Synapses}, Month = {Feb}, Number = {2}, Pages = {94-106}, pmid = {22251956}, Pst = {epublish}, Title = {Activity-dependent neurotransmitter respecification}, Volume = {13}, Year = {2012}, url = {papers/Spitzer_NatRevNeurosci2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn3154}} @article{Christensen:2013, Abstract = {IMPORTANCE: Valproate is used for the treatment of epilepsy and other neuropsychological disorders and may be the only treatment option for women of childbearing potential. However, prenatal exposure to valproate may increase the risk of autism. OBJECTIVE: To determine whether prenatal exposure to valproate is associated with an increased risk of autism in offspring. DESIGN, SETTING, AND PARTICIPANTS: Population-based study of all children born alive in Denmark from 1996 to 2006. National registers were used to identify children exposed to valproate during pregnancy and diagnosed with autism spectrum disorders (childhood autism [autistic disorder], Asperger syndrome, atypical autism, and other or unspecified pervasive developmental disorders). We analyzed the risks associated with all autism spectrum disorders as well as childhood autism. Data were analyzed by Cox regression adjusting for potential confounders (maternal age at conception, paternal age at conception, parental psychiatric history, gestational age, birth weight, sex, congenital malformations, and parity). Children were followed up from birth until the day of autism spectrum disorder diagnosis, death, emigration, or December 31, 2010, whichever came first. MAIN OUTCOMES AND MEASURES: Absolute risk (cumulative incidence) and the hazard ratio (HR) of autism spectrum disorder and childhood autism in children after exposure to valproate in pregnancy. RESULTS: Of 655,615 children born from 1996 through 2006, 5437 were identified with autism spectrum disorder, including 2067 with childhood autism. The mean age of the children at end of follow-up was 8.84 years (range, 4-14; median, 8.85). The estimated absolute risk after 14 years of follow-up was 1.53% (95% CI, 1.47%-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46%-0.51%) for childhood autism. Overall, the 508 children exposed to valproate had an absolute risk of 4.42% (95% CI, 2.59%-7.46%) for autism spectrum disorder (adjusted HR, 2.9 [95% CI, 1.7-4.9]) and an absolute risk of 2.50% (95% CI, 1.30%-4.81%) for childhood autism (adjusted HR, 5.2 [95% CI, 2.7-10.0]). When restricting the cohort to the 6584 children born to women with epilepsy, the absolute risk of autism spectrum disorder among 432 children exposed to valproate was 4.15% (95% CI, 2.20%-7.81%) (adjusted HR, 1.7 [95% CI, 0.9-3.2]), and the absolute risk of childhood autism was 2.95% (95% CI, 1.42%-6.11%) (adjusted HR, 2.9 [95% CI, 1.4-6.0]) vs 2.44% (95% CI, 1.88%-3.16%) for autism spectrum disorder and 1.02% (95% CI, 0.70%-1.49%) for childhood autism among 6152 children not exposed to valproate. CONCLUSIONS AND RELEVANCE: Maternal use of valproate during pregnancy was associated with a significantly increased risk of autism spectrum disorder and childhood autism in the offspring, even after adjusting for maternal epilepsy. For women of childbearing potential who use antiepileptic medications, these findings must be balanced against the treatment benefits for women who require valproate for epilepsy control.}, Author = {Christensen, Jakob and Gr{\o}nborg, Therese Koops and S{\o}rensen, Merete Juul and Schendel, Diana and Parner, Erik Thorlund and Pedersen, Lars Henning and Vestergaard, Mogens}, Date-Added = {2014-08-20 18:39:43 +0000}, Date-Modified = {2014-08-20 18:40:18 +0000}, Doi = {10.1001/jama.2013.2270}, Journal = {JAMA}, Journal-Full = {JAMA : the journal of the American Medical Association}, Keywords = {development; Human; fetal; infant; Child; epilepsy; spontaneous activity; Drug; wholeBrain}, Mesh = {Adolescent; Adult; Anticonvulsants; Autistic Disorder; Child; Child Development Disorders, Pervasive; Child, Preschool; Denmark; Epilepsy; Female; Follow-Up Studies; Humans; Incidence; Male; Maternal Age; Mental Disorders; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Registries; Risk; Valproic Acid; Young Adult}, Month = {Apr}, Number = {16}, Pages = {1696-703}, pmid = {23613074}, Pst = {ppublish}, Title = {Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism}, Volume = {309}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1001/jama.2013.2270}} @article{Meador:2013, Abstract = {BACKGROUND: Many women of childbearing potential take antiepileptic drugs, but the cognitive effects of fetal exposure are uncertain. We aimed to assess effects of commonly used antiepileptic drugs on cognitive outcomes in children up to 6 years of age. METHODS: In this prospective, observational, assessor-masked, multicentre study, we enrolled pregnant women with epilepsy on antiepileptic drug monotherapy (carbamazepine, lamotrigine, phenytoin, or valproate) between October, 1999, and February, 2004, at 25 epilepsy centres in the UK and the USA. Our primary outcome was intelligence quotient (IQ) at 6 years of age (age-6 IQ) in all children, assessed with linear regression adjusted for maternal IQ, antiepileptic drug type, standardised dose, gestational birth age, and use of periconceptional folate. We also assessed multiple cognitive domains and compared findings with outcomes at younger ages. This study is registered with ClinicalTrials.gov, number NCT00021866. FINDINGS: We included 305 mothers and 311 children (six twin pairs) in the primary analysis. 224 children completed 6 years of follow-up (6-year-completer sample). Multivariate analysis of all children showed that age-6 IQ was lower after exposure to valproate (mean 97, 95% CI 94-101) than to carbamazepine (105, 102-108; p=0·0015), lamotrigine (108, 105-110; p=0·0003), or phenytoin (108, 104-112; p=0·0006). Children exposed to valproate did poorly on measures of verbal and memory abilities compared with those exposed to the other antiepileptic drugs and on non-verbal and executive functions compared with lamotrigine (but not carbamazepine or phenytoin). High doses of valproate were negatively associated with IQ (r=-0·56, p<0·0001), verbal ability (r=-0·40, p=0·0045), non-verbal ability (r=-0·42, p=0·0028), memory (r=-0·30, p=0·0434), and executive function (r=-0·42, p=0·0004), but other antiepileptic drugs were not. Age-6 IQ correlated with IQs at younger ages, and IQ improved with age for infants exposed to any antiepileptic drug. Compared with a normative sample (173 [93%] of 187 children), right-handedness was less frequent in children in our study overall (185 [86%] of 215; p=0·0404) and in the lamotrigine (59 [83%] of 71; p=0·0287) and valproate (38 [79%] of 40; p=0·0089) groups. Verbal abilities were worse than non-verbal abilities in children in our study overall and in the lamotrigine and valproate groups. Mean IQs were higher in children exposed to periconceptional folate (108, 95% CI 106-111) than they were in unexposed children (101, 98-104; p=0·0009). INTERPRETATION: Fetal valproate exposure has dose-dependent associations with reduced cognitive abilities across a range of domains at 6 years of age. Reduced right-handedness and verbal (vs non-verbal) abilities might be attributable to changes in cerebral lateralisation induced by exposure to antiepileptic drugs. The positive association of periconceptional folate with IQ is consistent with other recent studies.}, Author = {Meador, Kimford J and Baker, Gus A and Browning, Nancy and Cohen, Morris J and Bromley, Rebecca L and Clayton-Smith, Jill and Kalayjian, Laura A and Kanner, Andres and Liporace, Joyce D and Pennell, Page B and Privitera, Michael and Loring, David W and {NEAD Study Group}}, Date-Added = {2014-08-20 18:38:00 +0000}, Date-Modified = {2014-08-20 18:39:13 +0000}, Doi = {10.1016/S1474-4422(12)70323-X}, Journal = {Lancet Neurol}, Journal-Full = {The Lancet. Neurology}, Keywords = {development; Human; fetal; infant; Child; epilepsy; spontaneous activity; Drug; wholeBrain}, Mesh = {Adult; Anticonvulsants; Child; Child Development; Child, Preschool; Cognition; Epilepsy; Female; Humans; Infant; Infant, Newborn; Male; Observation; Phenytoin; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Prospective Studies; Triazines}, Month = {Mar}, Number = {3}, Pages = {244-52}, Pmc = {PMC3684942}, pmid = {23352199}, Pst = {ppublish}, Title = {Fetal antiepileptic drug exposure and cognitive outcomes at age 6 years (NEAD study): a prospective observational study}, Volume = {12}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S1474-4422(12)70323-X}} @article{Bassett:2008, Abstract = {The complex organization of connectivity in the human brain is incompletely understood. Recently, topological measures based on graph theory have provided a new approach to quantify large-scale cortical networks. These methods have been applied to anatomical connectivity data on nonhuman species, and cortical networks have been shown to have small-world topology, associated with high local and global efficiency of information transfer. Anatomical networks derived from cortical thickness measurements have shown the same organizational properties of the healthy human brain, consistent with similar results reported in functional networks derived from resting state functional magnetic resonance imaging (MRI) and magnetoencephalographic data. Here we show, using anatomical networks derived from analysis of inter-regional covariation of gray matter volume in MRI data on 259 healthy volunteers, that classical divisions of cortex (multimodal, unimodal, and transmodal) have some distinct topological attributes. Although all cortical divisions shared nonrandom properties of small-worldness and efficient wiring (short mean Euclidean distance between connected regions), the multimodal network had a hierarchical organization, dominated by frontal hubs with low clustering, whereas the transmodal network was assortative. Moreover, in a sample of 203 people with schizophrenia, multimodal network organization was abnormal, as indicated by reduced hierarchy, the loss of frontal and the emergence of nonfrontal hubs, and increased connection distance. We propose that the topological differences between divisions of normal cortex may represent the outcome of different growth processes for multimodal and transmodal networks and that neurodevelopmental abnormalities in schizophrenia specifically impact multimodal cortical organization.}, Author = {Bassett, Danielle S and Bullmore, Edward and Verchinski, Beth A and Mattay, Venkata S and Weinberger, Daniel R and Meyer-Lindenberg, Andreas}, Date-Added = {2014-08-19 16:51:42 +0000}, Date-Modified = {2014-08-19 17:03:45 +0000}, Doi = {10.1523/JNEUROSCI.1929-08.2008}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {human; fMRI; graph theory; network analysis; Theoretical; wholeBrain; MRI; DTI}, Mesh = {Adult; Brain Mapping; Case-Control Studies; Cerebral Cortex; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Models, Neurological; Neural Pathways; Schizophrenia}, Month = {Sep}, Number = {37}, Pages = {9239-48}, Pmc = {PMC2878961}, pmid = {18784304}, Pst = {ppublish}, Title = {Hierarchical organization of human cortical networks in health and schizophrenia}, Volume = {28}, Year = {2008}, url = {papers/Bassett_JNeurosci2008.pdf}} @Software{Csardi:2013, Author = {Csardi, G.}, Date-Added = {2014-08-15 17:00:20 +0000}, Date-Modified = {2014-09-30 20:20:54 +0000}, Keywords = {Software}, Title = {igraph, The network analysis package}, Url = {http://igraph.org}, Year = {2013}} @article{Clauset:2004, Author = {Clauset, A. and Newman, M. E. J. and Moore, C.}, Date-Added = {2014-08-15 16:57:32 +0000}, Date-Modified = {2014-08-15 17:00:02 +0000}, Keywords = {Software}, Title = {Finding community structure in very large networks}, eprint = {http://arxiv.org/pdf/cond-mat/0408187v2.pdf}, Year = {2004}, url = {papers/Clauset_2004.pdf}} @Software{Dollar:2014, Author = {Doll{\'a}r, P.}, Date-Added = {2014-08-15 16:55:17 +0000}, Date-Modified = {2014-08-15 17:02:03 +0000}, Keywords = {Software}, Lastchecked = {2014-08}, Title = {Piotr's Image and Video Matlab Toolbox}, Url = {http://vision.ucsd.edu/~pdollar/toolbox/doc/index.html}, Year = {2014}} @inproceedings{Lucas:1981, Author = {Lucas, B. D. and Kanade, T.}, Booktitle = {International Joint Conference on Artificial Intelligence}, Date-Added = {2014-08-15 16:16:56 +0000}, Date-Modified = {2014-08-15 16:19:42 +0000}, Keywords = {Software}, Pages = {674-697}, Title = {An Iterative image registration technique with an application to stereo vision}, Year = {1981}, url = {papers/Lucas_1981.pdf}} @Software{Ackman:2014b, Author = {Ackman, James B}, Date-Added = {2014-08-15 15:47:46 +0000}, Date-Modified = {2014-08-15 17:19:28 +0000}, Keywords = {wholeBrain; Software}, Lastchecked = {2014-08}, Title = {wholeBrainDX, Image analysis suite for whole brain calcium imaging}, Url = {https://github.com/ackman678/wholeBrainDX}, Year = {2014}} @article{Newman:2004, Author = {Newman, M. E. J.}, Date-Added = {2014-08-11 23:45:12 +0000}, Date-Modified = {2014-08-11 23:47:08 +0000}, Doi = {10.1103/PhysRevE.69.066133}, Issue = {6}, Journal = {Phys. Rev. E}, Month = {Jun}, Numpages = {5}, Pages = {066133}, Publisher = {American Physical Society}, Title = {Fast algorithm for detecting community structure in networks}, eprint = {http://link.aps.org/doi/10.1103/PhysRevE.69.066133}, Volume = {69}, Year = {2004}, url = {papers/Newman_Phys.Rev.E2004.pdf}} @article{Gaspar:2003, Abstract = {New genetic models that target the serotonin system show that transient alterations in serotonin homeostasis cause permanent changes to adult behaviour and modify the fine wiring of brain connections. These findings have revived a long-standing interest in the developmental role of serotonin. Molecular genetic approaches are now showing us that different serotonin receptors, acting at different developmental stages, modulate different developmental processes such as neurogenesis, apoptosis, axon branching and dendritogenesis. Our understanding of the specification of the serotonergic phenotype is improving. In addition, studies have revealed that serotonergic traits are dissociable, as there are populations of neurons that contain serotonin but do not synthesize it.}, Author = {Gaspar, Patricia and Cases, Olivier and Maroteaux, Luc}, Date-Added = {2014-08-08 18:11:15 +0000}, Date-Modified = {2014-08-08 18:11:15 +0000}, Doi = {10.1038/nrn1256}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Aging; Animals; Behavior, Animal; Cell Aging; Embryo, Mammalian; Homeostasis; Humans; Mental Disorders; Mice; Molecular Biology; Neurons; Receptors, Serotonin; Serotonin}, Month = {Dec}, Number = {12}, Pages = {1002-12}, pmid = {14618156}, Pst = {ppublish}, Title = {The developmental role of serotonin: news from mouse molecular genetics}, Volume = {4}, Year = {2003}, url = {papers/Gaspar_NatRevNeurosci2003.pdf}} @article{Lebrand:1998, Abstract = {Neurons in first-order sensory thalamic nuclei have been shown to express functional plasma membrane serotonin (SERT) and vesicular monoamine (VMAT2) transporters during early postnatal development. In the present study, we provide an extensive description of the spatial and the temporal patterns of VMAT2 and SERT expression, during early embryonic development and postnatal life, by using in situ hybridization and immunocytochemistry. VMAT2 and SERT genes are transiently expressed in a wide population of non-monoaminergic neurons in the central and peripheral nervous system with a large overlap in the temporal and spatial pattern of expression of both genes. A selective pattern of expression of both genes was observed in the thalamus with expression limited to the dorsal thalamus and more particularly to primary sensory relay nuclei that convey point to point projection maps. Transient expression of the transporters was also observed in sensory cranial nerves, in the hippocampus, cerebral cortex, septum, and amygdala. VMAT2 and SERT gene expression was not necessarily linked, as some neural populations expressed only VMAT2, while others only contained SERT. Since VMAT2 serves to transport catecholamines besides serotonin, we examined the developmental expression of the plasma membrane dopamine and norepinephrine transporters but found no transient expression of these genes. Despite minor temporal disparities, VMAT2 and SERT extinguished almost simultaneously during the second and third weeks of post-natal life. These expressions did not seem to be dependent on peripheral neural inputs, since monocular enucleations and infraorbital nerve cuts effected on the day of birth, did not modify the period of transporter expression or of extinction.}, Author = {Lebrand, C and Cases, O and Wehrl{\'e}, R and Blakely, R D and Edwards, R H and Gaspar, P}, Date-Added = {2014-08-08 18:10:54 +0000}, Date-Modified = {2014-08-08 18:10:54 +0000}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Brain Chemistry; Carrier Proteins; Cell Membrane; Dopamine Plasma Membrane Transport Proteins; Eye Enucleation; Gene Expression Regulation, Developmental; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C3H; Nerve Tissue Proteins; Neurons, Afferent; Neuropeptides; Neurotransmitter Agents; Norepinephrine Plasma Membrane Transport Proteins; Prosencephalon; RNA, Messenger; Rats; Rats, Sprague-Dawley; Serotonin; Symporters; Thalamus; Time Factors; Trigeminal Nerve; Vesicular Biogenic Amine Transport Proteins; Vesicular Monoamine Transport Proteins; Vision, Monocular}, Month = {Nov}, Number = {4}, Pages = {506-24}, pmid = {9826275}, Pst = {ppublish}, Title = {Transient developmental expression of monoamine transporters in the rodent forebrain}, Volume = {401}, Year = {1998}, url = {papers/Lebrand_JCompNeurol1998.pdf}} @article{Lebrand:1996, Abstract = {Serotonin (5-HT) has been shown to affect the development and patterning of the mouse barrelfield. We show that the dense transient 5-HT innervation of the somatosensory, visual, and auditory cortices originates in the thalamus rather than in the raphe: 5-HT is detected in thalamocortical fibers and most 5-HT cortical labeling disappears after thalamic lesions. Thalamic neurons do not synthesize 5-HT but take up exogenous 5-HT through 5-HT high affinity uptake sites located on thalamocortical axons and terminals. 3H-5-HT injected into the cortex is retrogradely transported to thalamic neurons. In situ hybridization shows a transient expression of the genes encoding the serotonin transporter and the vesicular monoamine transporter in thalamic sensory neurons. In these glutamatergic neurons, internalized 5-HT might thus be stored and used as a "borrowed transmitter" for extraneuronal signaling or could exert an intraneuronal control on thalamic maturation.}, Author = {Lebrand, C and Cases, O and Adelbrecht, C and Doye, A and Alvarez, C and El Mestikawy, S and Seif, I and Gaspar, P}, Date-Added = {2014-08-08 18:10:17 +0000}, Date-Modified = {2014-08-08 18:12:12 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Age Factors; Animals; Antibody Specificity; Biological Transport; Carrier Proteins; Cerebral Cortex; Gene Expression; Immunohistochemistry; In Situ Hybridization; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Neurons, Afferent; Neuropeptides; Neurotransmitter Agents; RNA, Messenger; Rats; Rats, Sprague-Dawley; Serotonin; Serotonin Plasma Membrane Transport Proteins; Synaptic Vesicles; Thalamus; Time Factors; Tritium; Vesicular Biogenic Amine Transport Proteins; Vesicular Monoamine Transport Proteins; barrel cortex; topographic map; Visual Cortex; Auditory Cortex; wholeBrain}, Month = {Nov}, Number = {5}, Pages = {823-35}, pmid = {8938116}, Pst = {ppublish}, Title = {Transient uptake and storage of serotonin in developing thalamic neurons}, Volume = {17}, Year = {1996}, url = {papers/Lebrand_Neuron1996.pdf}} @article{Newman:2000, Abstract = {The small-world network model is a simple model of the structure of social networks, which possesses characteristics of both regular lattices and random graphs. The model consists of a one-dimensional lattice with a low density of shortcuts added between randomly selected pairs of points. These shortcuts greatly reduce the typical path length between any two points on the lattice. We present a mean-field solution for the average path length and for the distribution of path lengths in the model. This solution is exact in the limit of large system size and either a large or small number of shortcuts.}, Author = {Newman, M E and Moore, C and Watts, D J}, Date-Added = {2014-08-06 18:24:59 +0000}, Date-Modified = {2014-08-06 18:24:59 +0000}, Journal = {Phys Rev Lett}, Journal-Full = {Physical review letters}, Mesh = {Computer Simulation; Humans; Mathematics; Models, Theoretical; Neural Networks (Computer); Social Behavior}, Month = {Apr}, Number = {14}, Pages = {3201-4}, pmid = {11019047}, Pst = {ppublish}, Title = {Mean-field solution of the small-world network model}, Volume = {84}, Year = {2000}, url = {papers/Newman_PhysRevLett2000.pdf}} @article{Humphries:2008, Abstract = {BACKGROUND: Many technological, biological, social, and information networks fall into the broad class of 'small-world' networks: they have tightly interconnected clusters of nodes, and a shortest mean path length that is similar to a matched random graph (same number of nodes and edges). This semi-quantitative definition leads to a categorical distinction ('small/not-small') rather than a quantitative, continuous grading of networks, and can lead to uncertainty about a network's small-world status. Moreover, systems described by small-world networks are often studied using an equivalent canonical network model--the Watts-Strogatz (WS) model. However, the process of establishing an equivalent WS model is imprecise and there is a pressing need to discover ways in which this equivalence may be quantified. METHODOLOGY/PRINCIPAL FINDINGS: We defined a precise measure of 'small-world-ness' S based on the trade off between high local clustering and short path length. A network is now deemed a 'small-world' if S>1--an assertion which may be tested statistically. We then examined the behavior of S on a large data-set of real-world systems. We found that all these systems were linked by a linear relationship between their S values and the network size n. Moreover, we show a method for assigning a unique Watts-Strogatz (WS) model to any real-world network, and show analytically that the WS models associated with our sample of networks also show linearity between S and n. Linearity between S and n is not, however, inevitable, and neither is S maximal for an arbitrary network of given size. Linearity may, however, be explained by a common limiting growth process. CONCLUSIONS/SIGNIFICANCE: We have shown how the notion of a small-world network may be quantified. Several key properties of the metric are described and the use of WS canonical models is placed on a more secure footing.}, Author = {Humphries, Mark D and Gurney, Kevin}, Date-Added = {2014-08-06 18:22:59 +0000}, Date-Modified = {2014-08-06 18:22:59 +0000}, Doi = {10.1371/journal.pone.0002051}, Journal = {PLoS One}, Journal-Full = {PloS one}, Mesh = {Metric System; Models, Biological}, Number = {4}, Pages = {e0002051}, Pmc = {PMC2323569}, pmid = {18446219}, Pst = {epublish}, Title = {Network 'small-world-ness': a quantitative method for determining canonical network equivalence}, Volume = {3}, Year = {2008}, url = {papers/Humphries_PLoSOne2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0002051}} @article{Sporns:2004, Abstract = {Recent research has revealed general principles in the structural and functional organization of complex networks which are shared by various natural, social and technological systems. This review examines these principles as applied to the organization, development and function of complex brain networks. Specifically, we examine the structural properties of large-scale anatomical and functional brain networks and discuss how they might arise in the course of network growth and rewiring. Moreover, we examine the relationship between the structural substrate of neuroanatomy and more dynamic functional and effective connectivity patterns that underlie human cognition. We suggest that network analysis offers new fundamental insights into global and integrative aspects of brain function, including the origin of flexible and coherent cognitive states within the neural architecture.}, Author = {Sporns, Olaf and Chialvo, Dante R and Kaiser, Marcus and Hilgetag, Claus C}, Date-Added = {2014-08-06 17:59:01 +0000}, Date-Modified = {2014-08-06 17:59:01 +0000}, Doi = {10.1016/j.tics.2004.07.008}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Mesh = {Brain; Cognition; Humans; Nerve Net}, Month = {Sep}, Number = {9}, Pages = {418-25}, pmid = {15350243}, Pst = {ppublish}, Title = {Organization, development and function of complex brain networks}, Volume = {8}, Year = {2004}, url = {papers/Sporns_TrendsCognSci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2004.07.008}} @article{Lim:2013, Abstract = {Human brain maturation is characterized by the prolonged development of structural and functional properties of large-scale networks that extends into adulthood. However, it is not clearly understood which features change and which remain stable over time. Here, we examined structural connectivity based on diffusion tensor imaging (DTI) in 121 participants between 4 and 40 years of age. DTI data were analyzed for small-world parameters, modularity, and the number of fiber tracts at the level of streamlines. First, our findings showed that the number of fiber tracts, small-world topology, and modular organization remained largely stable despite a substantial overall decrease in the number of streamlines with age. Second, this decrease mainly affected fiber tracts that had a large number of streamlines, were short, within modules and within hemispheres; such connections were affected significantly more often than would be expected given their number of occurrences in the network. Third, streamline loss occurred earlier in females than in males. In summary, our findings suggest that core properties of structural brain connectivity, such as the small-world and modular organization, remain stable during brain maturation by focusing streamline loss to specific types of fiber tracts.}, Author = {Lim, Sol and Han, Cheol E and Uhlhaas, Peter J and Kaiser, Marcus}, Date-Added = {2014-08-05 13:08:30 +0000}, Date-Modified = {2014-08-05 13:09:21 +0000}, Doi = {10.1093/cercor/bht333}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {brain connectivity; connectome; maturation; network analysis; tractography; resting state; default mode network; technique; Methods; computation biology; Theoretical; graph theory; human; fmri; Software; neonate; Cerebral Cortex; Neocortex; wholeBrain}, Month = {Dec}, pmid = {24343892}, Pst = {aheadofprint}, Title = {Preferential Detachment During Human Brain Development: Age- and Sex-Specific Structural Connectivity in Diffusion Tensor Imaging (DTI) Data}, Year = {2013}, url = {papers/Lim_CerebCortex2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bht333}} @article{Heuvel:2014, Abstract = {The human connectome is the result of an elaborate developmental trajectory. Acquiring diffusion-weighted imaging and resting-state fMRI, we studied connectome formation during the preterm phase of macroscopic connectome genesis. In total, 27 neonates were scanned at week 30 and/or week 40 gestational age (GA). Examining the architecture of the neonatal anatomical brain network revealed a clear presence of a small-world modular organization before term birth. Analysis of neonatal functional connectivity (FC) showed the early formation of resting-state networks, suggesting that functional networks are present in the preterm brain, albeit being in an immature state. Moreover, structural and FC patterns of the neonatal brain network showed strong overlap with connectome architecture of the adult brain (85 and 81%, respectively). Analysis of brain development between week 30 and week 40 GA revealed clear developmental effects in neonatal connectome architecture, including a significant increase in white matter microstructure (P < 0.01), small-world topology (P < 0.01) and interhemispheric FC (P < 0.01). Computational analysis further showed that developmental changes involved an increase in integration capacity of the connectivity network as a whole. Taken together, we conclude that hallmark organizational structures of the human connectome are present before term birth and subject to early development.}, Author = {van den Heuvel, Martijn P and Kersbergen, Karina J and de Reus, Marcel A and Keunen, Kristin and Kahn, Ren{\'e} S and Groenendaal, Floris and de Vries, Linda S and Benders, Manon J N L}, Date-Added = {2014-08-05 13:07:41 +0000}, Date-Modified = {2014-08-05 13:09:49 +0000}, Doi = {10.1093/cercor/bhu095}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {connectome; development; functional connectivity; neonatal; structural connectivity; resting state; default mode network; technique; Methods; computation biology; Theoretical; graph theory; human; fmri; Software; neonate; Cerebral Cortex; Neocortex; wholeBrain}, Month = {May}, pmid = {24833018}, Pst = {aheadofprint}, Title = {The Neonatal Connectome During Preterm Brain Development}, Year = {2014}, url = {papers/Heuvel_CerebCortex2014.pdf}} @article{Doria:2010, Abstract = {The functions of the resting state networks (RSNs) revealed by functional MRI remain unclear, but it has seemed possible that networks emerge in parallel with the development of related cognitive functions. We tested the alternative hypothesis: that the full repertoire of resting state dynamics emerges during the period of rapid neural growth before the normal time of birth at term (around 40 wk of gestation). We used a series of independent analytical techniques to map in detail the development of different networks in 70 infants born between 29 and 43 wk of postmenstrual age (PMA). We characterized and charted the development of RSNs from recognizable but often fragmentary elements at 30 wk of PMA to full facsimiles of adult patterns at term. Visual, auditory, somatosensory, motor, default mode, frontoparietal, and executive control networks developed at different rates; however, by term, complete networks were present, several of which were integrated with thalamic activity. These results place the emergence of RSNs largely during the period of rapid neural growth in the third trimester of gestation, suggesting that they are formed before the acquisition of cognitive competencies in later childhood.}, Author = {Doria, Valentina and Beckmann, Christian F and Arichi, Tomoki and Merchant, Nazakat and Groppo, Michela and Turkheimer, Federico E and Counsell, Serena J and Murgasova, Maria and Aljabar, Paul and Nunes, Rita G and Larkman, David J and Rees, Geraint and Edwards, A David}, Date-Added = {2014-08-05 13:06:37 +0000}, Date-Modified = {2014-08-05 13:09:57 +0000}, Doi = {10.1073/pnas.1007921107}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {resting state; default mode network; technique; Methods; computation biology; Theoretical; graph theory; human; fmri; Software; neonate; Cerebral Cortex; Neocortex; wholeBrain}, Mesh = {Bias (Epidemiology); Brain; Female; Gestational Age; Humans; Infant; Nerve Net; Pregnancy; Pregnancy Trimester, Third; Premature Birth; Regression Analysis; Rest}, Month = {Nov}, Number = {46}, Pages = {20015-20}, Pmc = {PMC2993415}, pmid = {21041625}, Pst = {ppublish}, Title = {Emergence of resting state networks in the preterm human brain}, Volume = {107}, Year = {2010}, url = {papers/Doria_ProcNatlAcadSciUSA2010.pdf}} @article{Ko:2014, Abstract = {In primary visual cortex (V1), connectivity between layer 2/3 (L2/3) excitatory neurons undergoes extensive reorganization after the onset of visual experience whereby neurons with similar feature selectivity form functional microcircuits (Ko et al., 2011, 2013). It remains unknown whether visual experience is required for the developmental refinement of intracortical circuitry or whether this maturation is guided intrinsically. Here, we correlated the connectivity between V1 L2/3 neurons assayed by simultaneous whole-cell recordings in vitro to their response properties measured by two-photon calcium imaging in vivo in dark-reared mice. We found that neurons with similar responses to oriented gratings or natural movies became preferentially connected in the absence of visual experience. However, the relationship between connectivity and similarity of visual responses to natural movies was not as strong in dark-reared as in normally reared mice. Moreover, dark rearing prevented the normally occurring loss of connections between visually nonresponsive neurons after eye opening (Ko et al., 2013). Therefore, our data suggest that the absence of visual input does not prevent the emergence of functionally specific recurrent connectivity in cortical circuits; however, visual experience is required for complete microcircuit maturation.}, Author = {Ko, Ho and Mrsic-Flogel, Thomas D and Hofer, Sonja B}, Date-Added = {2014-07-28 15:16:50 +0000}, Date-Modified = {2014-07-28 15:16:50 +0000}, Doi = {10.1523/JNEUROSCI.0875-14.2014}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {experience-dependent; functional microcircuit organization; microcircuit development; mouse visual cortex; synaptic connectivity; two-photon imaging}, Month = {Jul}, Number = {29}, Pages = {9812-6}, pmid = {25031418}, Pst = {ppublish}, Title = {Emergence of feature-specific connectivity in cortical microcircuits in the absence of visual experience}, Volume = {34}, Year = {2014}, url = {papers/Ko_JNeurosci2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0875-14.2014}} @article{Nasiriavanaki:2014, Abstract = {The increasing use of mouse models for human brain disease studies presents an emerging need for a new functional imaging modality. Using optical excitation and acoustic detection, we developed a functional connectivity photoacoustic tomography system, which allows noninvasive imaging of resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight functional regions, including the olfactory bulb, limbic, parietal, somatosensory, retrosplenial, visual, motor, and temporal regions, as well as in several subregions. The borders and locations of these regions agreed well with the Paxinos mouse brain atlas. By subjecting the mouse to alternating hyperoxic and hypoxic conditions, strong and weak functional connectivities were observed, respectively. In addition to connectivity images, vascular images were simultaneously acquired. These studies show that functional connectivity photoacoustic tomography is a promising, noninvasive technique for functional imaging of the mouse brain.}, Author = {Nasiriavanaki, Mohammadreza and Xia, Jun and Wan, Hanlin and Bauer, Adam Quentin and Culver, Joseph P and Wang, Lihong V}, Date-Added = {2014-07-28 14:38:23 +0000}, Date-Modified = {2014-07-28 14:39:12 +0000}, Doi = {10.1073/pnas.1311868111}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {RSFC; fcPAT; hyperoxia; hypoxia; mouse brain functional imaging; wholeBrain; topographic map; parcellation; optical physiology}, Mesh = {Algorithms; Animals; Anoxia; Brain; Brain Mapping; Disease Models, Animal; Electrodes; Equipment Design; Hemodynamics; Hemoglobins; Hyperoxia; Image Processing, Computer-Assisted; Lasers; Male; Mice; Neural Pathways; Normal Distribution; Photoacoustic Techniques}, Month = {Jan}, Number = {1}, Pages = {21-6}, Pmc = {PMC3890828}, pmid = {24367107}, Pst = {ppublish}, Title = {High-resolution photoacoustic tomography of resting-state functional connectivity in the mouse brain}, Volume = {111}, Year = {2014}, url = {papers/Nasiriavanaki_ProcNatlAcadSciUSA2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1311868111}} @article{Mohns:2008, Abstract = {The neonatal hippocampus exhibits regularly recurring waves of synchronized neuronal activity in vitro. Because active sleep (AS), characterized by bursts of phasic motor activity in the form of myoclonic twitching, may provide conditions that are conducive to activity-dependent development of hippocampal circuits, we hypothesized that the waves of synchronous neuronal activity that have been observed in vitro would be associated with AS-related twitching. Using unanesthetized 1- to 12-d-old rats, we report here that the majority of neurons in CA1 and the dentate gyrus (DG) are significantly more active during AS than during either quiet sleep or wakefulness. Neuronal activity typically occurs in phasic bursts, during which most neurons are significantly cross-correlated both within and across the CA1 and DG fields. All AS-active neurons increase their firing rates during periods of myoclonic twitching of the limbs, and a subset of these neurons exhibit a burst of activity immediately after limb twitches, suggesting that the twitches themselves provide sensory feedback to the infant hippocampus, as occurs in the infant spinal cord and neocortex. Finally, the synchronous bursts of neuronal activity are coupled to the emergence of the AS-related hippocampal gamma rhythm during the first postnatal week, as well as the emergence of the AS-related theta rhythm during the second postnatal week. We hypothesize that the phasic motor events of active sleep provide the developing hippocampus with discrete sensory stimulation that contributes to the development and refinement of hippocampal circuits as well as the development of synchronized interactions between hippocampus and neocortex.}, Author = {Mohns, Ethan J and Blumberg, Mark S}, Date-Added = {2014-07-25 15:34:41 +0000}, Date-Modified = {2014-07-25 15:34:41 +0000}, Doi = {10.1523/JNEUROSCI.1967-08.2008}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Action Potentials; Animals; Animals, Newborn; Hippocampus; Male; Neurons; Rats; Rats, Sprague-Dawley; Sleep; Theta Rhythm}, Month = {Oct}, Number = {40}, Pages = {10134-44}, Pmc = {PMC2678192}, pmid = {18829971}, Pst = {ppublish}, Title = {Synchronous bursts of neuronal activity in the developing hippocampus: modulation by active sleep and association with emerging gamma and theta rhythms}, Volume = {28}, Year = {2008}, url = {papers/Mohns_JNeurosci2008.pdf}} @article{Karlsson:2005, Abstract = {Sleep is a poorly understood behavior that predominates during infancy but is studied almost exclusively in adults. One perceived impediment to investigations of sleep early in ontogeny is the absence of state-dependent neocortical activity. Nonetheless, in infant rats, sleep is reliably characterized by the presence of tonic (i.e., muscle atonia) and phasic (i.e., myoclonic twitching) components; the neural circuitry underlying these components, however, is unknown. Recently, we described a medullary inhibitory area (MIA) in week-old rats that is necessary but not sufficient for the normal expression of atonia. Here we report that the infant MIA receives projections from areas containing neurons that exhibit state-dependent activity. Specifically, neurons within these areas, including the subcoeruleus (SubLC), pontis oralis (PO), and dorsolateral pontine tegmentum (DLPT), exhibit discharge profiles that suggest causal roles in the modulation of muscle tone and the production of myoclonic twitches. Indeed, lesions in the SubLC and PO decreased the expression of muscle atonia without affecting twitching (resulting in "REM sleep without atonia"), whereas lesions of the DLPT increased the expression of atonia while decreasing the amount of twitching. Thus, the neural substrates of infant sleep are strikingly similar to those of adults, a surprising finding in light of theories that discount the contribution of supraspinal neural elements to sleep before the onset of state-dependent neocortical activity.}, Author = {Karlsson, Karl A E and Gall, Andrew J and Mohns, Ethan J and Seelke, Adele M H and Blumberg, Mark S}, Date-Added = {2014-07-25 15:32:42 +0000}, Date-Modified = {2014-07-25 15:32:42 +0000}, Doi = {10.1371/journal.pbio.0030143}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Mesh = {Aging; Animals; Animals, Newborn; Female; Locus Coeruleus; Male; Medulla Oblongata; Muscle Tonus; Neurons; Pons; Rats; Rats, Sprague-Dawley; Sleep}, Month = {May}, Number = {5}, Pages = {e143}, Pmc = {PMC1079781}, pmid = {15826218}, Pst = {ppublish}, Title = {The neural substrates of infant sleep in rats}, Volume = {3}, Year = {2005}, url = {papers/Karlsson_PLoSBiol2005.pdf}} @article{Mohns:2006, Abstract = {Recent findings in infant rats suggest that the preoptic area (POA) and/or basal forebrain (BF) contribute to developmental changes in sleep and wake organization between postnatal day 2 (P2) and P9. To examine the contributions of these forebrain areas to sleep and wakefulness, separate lesions of the POA or BF, or combined lesions (POA + BF), were performed at P9, and precollicular transections were performed at P2. In addition, modafinil, a drug of unknown mechanism of action the effects of which on sleep and wakefulness have been hypothesized to result from inhibition of POA activity, was administered at P2 and P9. Finally, extracellular neuronal activity was recorded from the POA and BF. POA lesions decreased sleep bout durations and increased wake bout durations. BF lesions inhibited sleep bout durations to a lesser extent, while leaving wake bout durations unaffected. POA + BF lesions produced a combination of these effects, resulting in short bouts of sleep and wakefulness similar to those of transected P8 rats. Even at P2, transections decreased sleep bout durations. The finding, however, that the sleep-inhibiting and wake-promoting effects of modafinil were more potent at P9 than at P2 suggests increasing sleep-wake modulation by the POA between these two ages. Finally, neuronal recordings confirmed the presence of state-dependent neurons within the infant POA and BF. We propose that the POA, in addition to promoting sleep, inhibits wakefulness via direct and indirect inhibitory connections with wake-promoting neurons in the BF, and that this inhibitory influence increases across early development.}, Author = {Mohns, Ethan J and Karlsson, Karl A E and Blumberg, Mark S}, Date-Added = {2014-07-25 15:31:44 +0000}, Date-Modified = {2014-07-25 15:31:44 +0000}, Doi = {10.1111/j.1460-9568.2006.04652.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Mesh = {Animals; Animals, Newborn; Benzhydryl Compounds; Central Nervous System Stimulants; Electromyography; Male; Neurons; Preoptic Area; Prosencephalon; Rats; Rats, Sprague-Dawley; Sleep; Wakefulness}, Month = {Mar}, Number = {5}, Pages = {1301-10}, Pmc = {PMC2645537}, pmid = {16553791}, Pst = {ppublish}, Title = {The preoptic hypothalamus and basal forebrain play opposing roles in the descending modulation of sleep and wakefulness in infant rats}, Volume = {23}, Year = {2006}, url = {papers/Mohns_EurJNeurosci2006.pdf}} @article{Woolsey:1978, Author = {Woolsey, T A}, Date-Added = {2014-07-25 15:19:46 +0000}, Date-Modified = {2014-07-25 15:19:46 +0000}, Journal = {Brain Behav Evol}, Journal-Full = {Brain, behavior and evolution}, Mesh = {Bibliography as Topic; History, 20th Century; Psychophysiology; United States}, Number = {4}, Pages = {307-24}, pmid = {359102}, Pst = {ppublish}, Title = {C. N. Woolsey--scientist and artist: a complete bibliography (1933--1974)}, Volume = {15}, Year = {1978}, url = {papers/Woolsey_BrainBehavEvol1978.pdf}} @book{Harlow:1958, Annote = {http://hdl.handle.net/10079/bibid/5224793 From http://braininfo.rprc.washington.edu/Source.aspx?ID=90&questID=1350: >This paper discusses and illustrates the topographic representation of somesthetic and motor functions in the cerebral cortex of several nonhuman species. Somesthetic function was mapped in anesthetized animals on the basis of evoked potentials elicited in the cortex by light touch stimulation of the skin. Motor function was mapped also in anesthetized animals on the basis of movements elicited by electrical stimulation of the cortex. The report provides summary diagrams in which the size and locations of cortical areas related to specific skin areas are mapped on the cortical surface. The primary somesthetic area (area SI of Woolsey-1958), second somatic sensory area (area SII of Woolsey-1958), primary motor cortex (area MI of Woolsey-1958) and supplementary motor cortex (area MII of Woolsey-1958) are illustrated for the rat, rabbit, cat and macaque with highly detailed illustrations of the primary somesthetic and motor areas in the macaque.}, Author = {Harlow, H.F. and Woolsey, C.N.}, Date-Added = {2014-07-25 14:58:38 +0000}, Date-Modified = {2018-01-16 22:24:29 +0000}, Keywords = {Somatosensory Cortex; topographic map; neurophysiology; Neocortex; mouse; rat;}, Lccn = {58013447}, Publisher = {University of Wisconsin Press}, Title = {Biological and biochemical bases of behavior}, eprint = {http://books.google.com/books?id=L8M0AAAAMAAJ}, Year = {1958}, url = {papers/Harlow_1958.pdf}, Bdsk-Url-1 = {http://braininfo.rprc.washington.edu/Source.aspx?ID=90&questID=1350}} @article{Wong-Riley:1980, Abstract = {The posteromedial barrel subfield of the somatosensory cortex of mice was examined histochemically for cytochrome oxidase activity (cytochrome c oxidase; ferrocytochrome c:oxygen oxidoreductase, EC 1.9.3.1). In normal mice a high enzymatic activity was found within the barrel hollows, rather than in the sides and septa. Electron microscopic examination indicated that within the hollows reactive mitochondria reside in many dendrites, in some axonal terminals, and in a few neuronal perikarya. After neonatal cauterization of selected row(s) of vibrissae, the corresponding row(s) of barrels appeared as narrowed fused band(s) and their cytochrome oxidase activity was much reduced. Removal of vibrissae in the adult, by either cauterization or repeated plucking, did not cause size changes of cortical barrels. However, there was a significant decrease in the oxidative enzymatic activity within these barrels. Thus, the deprivation of sensory input through damage to, or removal of, the peripheral sensory organ induces an enzymatic response in neurons that are at least two to three synapses away from the periphery.}, Author = {Wong-Riley, M T and Welt, C}, Date-Added = {2014-07-25 14:28:21 +0000}, Date-Modified = {2014-07-25 14:28:21 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Mesh = {Animals; Electron Transport Complex IV; Hair; Mechanoreceptors; Mice; Neural Pathways; Somatosensory Cortex}, Month = {Apr}, Number = {4}, Pages = {2333-7}, Pmc = {PMC348709}, pmid = {6246540}, Pst = {ppublish}, Title = {Histochemical changes in cytochrome oxidase of cortical barrels after vibrissal removal in neonatal and adult mice}, Volume = {77}, Year = {1980}, url = {papers/Wong-Riley_ProcNatlAcadSciUSA1980.pdf}} @article{Woolsey:1967, Author = {Woolsey, T A}, Date-Added = {2014-07-25 14:12:38 +0000}, Date-Modified = {2014-07-25 14:12:38 +0000}, Journal = {Johns Hopkins Med J}, Journal-Full = {The Johns Hopkins medical journal}, Mesh = {Anatomy, Comparative; Animals; Cerebral Cortex; Electrophysiology; Evoked Potentials; Golgi Apparatus; Mice; Rabbits; Rodentia; Sensation; Vestibulocochlear Nerve; Visual Perception}, Month = {Aug}, Number = {2}, Pages = {91-112}, pmid = {6032827}, Pst = {ppublish}, Title = {Somatosensory, auditory and visual cortical areas of the mouse}, Volume = {121}, Year = {1967}, url = {papers/Woolsey_JohnsHopkinsMedJ1967.pdf}} @article{Woolsey:1970a, Author = {Woolsey, T A and Van der Loos, H}, Date-Added = {2014-07-25 14:06:21 +0000}, Date-Modified = {2014-07-25 14:06:43 +0000}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {Histological Techniques;Sensation;Biometry;Terminology;K;Electrodes;Hair;Animal;Evoked Potentials;Cerebral Cortex/*cytology/physiology;Surface Properties;Mice;16 Barrels}, Mesh = {Animals; Biometry; Cerebral Cortex; Electrodes; Evoked Potentials; Hair; Histological Techniques; Mice; Sensation; Surface Properties; Terminology as Topic}, Month = {Jan}, Number = {2}, Pages = {205-42}, pmid = {4904874}, Pst = {ppublish}, Title = {The structural organization of layer IV in the somatosensory region (SI) of mouse cerebral cortex. The description of a cortical field composed of discrete cytoarchitectonic units}, Volume = {17}, Year = {1970}, url = {papers/Woolsey_BrainRes1970.pdf}} @article{Narboux-Neme:2008, Abstract = {The serotonin transporter gene (SLC6A4; synonyms, SERT, 5-HTT) is expressed much more broadly during development than in adulthood. To obtain a full picture of all sites of SERT expression during development we used a new mouse model where Cre recombinase was inserted into the gene encoding the serotonin transporter. Two reporter mouse lines, ROSA26R and the Tau(mGFP), allowed to map all the cells that express SERT at any point during development. Combined LacZ histochemistry and GFP immunolabelling showed neuronal cell bodies and axon fiber tracts. Earliest recombination in embryos was visible in the periphery in the heart and liver by E10.5 followed by recombination in the brain in raphe serotonergic neurons by E12.5. Further, recombination in non-serotonin neurons was visible in the choroid plexus, roof plate, and neural crest derivatives; by E15.5, recombination was found in the dorsal thalamus, cingulate cortex, CA3 field of the hippocampus, retinal ganglion cells, superior olivary nucleus and cochlear nucleus. Postnatally, SERT mediated recombination was visible in the medial prefrontal cortex and layer VI neurons in the isocortex. Recombined cells were co-labelled with Neu-N, but not with GAD67, and were characterized by long range projections (corpus callosum, fornix, thalamocortical). This fate map of serotonin transporter expressing cells emphasizes the broad expression of SERT in non-serotonin neurons during development and clarifies the localization of SERT expression in the hippocampus and limbic cortex. The identification of targets of SSRIs and serotonin releasers during embryonic and early postnatal life helps understanding the very diverse physiological consequences of administration of these drugs during development.}, Author = {Narboux-N{\^e}me, Nicolas and Pavone, Luigi Michele and Avallone, Luigi and Zhuang, Xiaoxi and Gaspar, Patricia}, Date-Added = {2014-07-25 13:43:02 +0000}, Date-Modified = {2014-07-25 13:43:59 +0000}, Doi = {10.1016/j.neuropharm.2008.08.020}, Journal = {Neuropharmacology}, Journal-Full = {Neuropharmacology}, Keywords = {grant; ideas; thalamocortical; Thalamic Nuclei; Neocortex; barrels; Somatosensory Cortex; topographic map}, Mesh = {Animals; Embryo, Mammalian; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Integrases; Mice; Mice, Transgenic; Neurons; Raphe Nuclei; Serotonin; Serotonin Plasma Membrane Transport Proteins; Serotonin Uptake Inhibitors; tau Proteins}, Month = {Nov}, Number = {6}, Pages = {994-1005}, pmid = {18789954}, Pst = {ppublish}, Title = {Serotonin transporter transgenic (SERTcre) mouse line reveals developmental targets of serotonin specific reuptake inhibitors (SSRIs)}, Volume = {55}, Year = {2008}, url = {papers/Narboux-Nême_Neuropharmacology2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuropharm.2008.08.020}} @article{Zhuang:2005, Abstract = {We used a knock-in strategy to generate two lines of mice expressing Cre recombinase under the transcriptional control of the dopamine transporter promoter (DAT-cre mice) or the serotonin transporter promoter (SERT-cre mice). In DAT-cre mice, immunocytochemical staining of adult brains for the dopamine-synthetic enzyme tyrosine hydroxylase and for Cre recombinase revealed that virtually all dopaminergic neurons in the ventral midbrain expressed Cre. Crossing DAT-cre mice with ROSA26-stop-lacZ or ROSA26-stop-YFP reporter mice revealed a near perfect correlation between staining for tyrosine hydroxylase and beta-galactosidase or YFP. YFP-labeled fluorescent dopaminergic neurons could be readily identified in live slices. Crossing SERT-cre mice with the ROSA26-stop-lacZ or ROSA26-stop-YFP reporter mice similarly revealed a near perfect correlation between staining for serotonin-synthetic enzyme tryptophan hydroxylase and beta-galactosidase or YFP. Additional Cre expression in the thalamus and cortex was observed, reflecting the known pattern of transient SERT expression during early postnatal development. These findings suggest a general strategy of using neurotransmitter transporter promoters to drive selective Cre expression and thus control mutations in specific neurotransmitter systems. Crossed with fluorescent-gene reporters, this strategy tags neurons by neurotransmitter status, providing new tools for electrophysiology and imaging.}, Author = {Zhuang, Xiaoxi and Masson, Justine and Gingrich, Jay A and Rayport, Stephen and Hen, Ren{\'e}}, Date-Added = {2014-07-25 13:38:19 +0000}, Date-Modified = {2014-07-25 13:38:19 +0000}, Doi = {10.1016/j.jneumeth.2004.09.020}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Mesh = {Animals; Brain; Chimera; Dopamine; Dopamine Plasma Membrane Transport Proteins; Female; Gene Expression Regulation; Gene Targeting; Genes, Reporter; Integrases; Male; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Biology; Nerve Tissue Proteins; Neurochemistry; Neurons; Promoter Regions, Genetic; Recombinant Fusion Proteins; Serotonin; Serotonin Plasma Membrane Transport Proteins; Tyrosine 3-Monooxygenase; beta-Galactosidase}, Month = {Apr}, Number = {1}, Pages = {27-32}, pmid = {15763133}, Pst = {ppublish}, Title = {Targeted gene expression in dopamine and serotonin neurons of the mouse brain}, Volume = {143}, Year = {2005}, url = {papers/Zhuang_JNeurosciMethods2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2004.09.020}} @article{Li:2013b, Abstract = {A dynamic interplay between intrinsic regional molecular cues and extrinsic factors from the thalamus shape multiple features of early cortical development. It remains uncertain and controversial, however, whether the initial formation of cortical columns depends on neuronal activity, and there is little evidence that cortical lamination or neuronal differentiation is influenced by extrinsic activity. We examined the role of thalamic-derived factors in cortical development by selectively eliminating glutamatergic synaptic transmission from thalamocortical neurons in mice and found that eliminating thalamocortical neurotransmission prevented the formation of "barrel" columns in somatosensory cortex. Interestingly, based on cytoarchitectonic criteria and genetic markers, blocking thalamocortical neurotransmission also perturbed the development of superficial cortical lamina and the morphologic development of neurons. These experiments demonstrate that barrels and aspects of the layer-dependent pattern of cortical cytoarchitecture, gene expression, and neuronal differentiation depend on thalamocortical neurotransmission, extending the apparent influence of extrinsic, presumably activity-dependent factors, on cortical development.}, Author = {Li, Hong and Fertuzinhos, Sofia and Mohns, Ethan and Hnasko, Thomas S and Verhage, Matthijs and Edwards, Robert and Sestan, Nenad and Crair, Michael C}, Date-Added = {2014-07-25 13:37:09 +0000}, Date-Modified = {2014-07-25 13:37:09 +0000}, Doi = {10.1016/j.neuron.2013.06.043}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Evoked Potentials, Somatosensory; Glutamic Acid; Mice; Neural Pathways; Neurons; Somatosensory Cortex; Synaptic Transmission; Thalamus}, Month = {Sep}, Number = {5}, Pages = {970-86}, Pmc = {PMC3768017}, pmid = {24012009}, Pst = {ppublish}, Title = {Laminar and columnar development of barrel cortex relies on thalamocortical neurotransmission}, Volume = {79}, Year = {2013}, url = {papers/Li_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.06.043}} @article{Kobayashi:1963, Author = {Kobayashi, T}, Date-Added = {2014-07-11 13:17:40 +0000}, Date-Modified = {2014-07-11 13:33:27 +0000}, Journal = {Am J Physiol}, Journal-Full = {The American journal of physiology}, Keywords = {BODY WEIGHT; BRAIN; GROWTH; mouse; mice; Cerebral Cortex; postnatal; development; human}, Mesh = {Body Weight; Brain; Growth}, Month = {Feb}, Pages = {343-6}, pmid = {14033949}, Pst = {ppublish}, Title = {Brain-to-body ratios and time of maturation of the mouse brain}, Volume = {204}, Year = {1963}, url = {papers/KOBAYASHI_AmJPhysiol1963.pdf}} @article{Bai:2008, Abstract = {During forebrain development the lateral cortical stream (LCS) supplies neurons to structures in the ventral telencephalon including the amygdala and piriform cortex. In the current study, we used spatially directed in utero electroporation and RNAi to investigate mechanisms of migration to the ventral telencephalon. Cells labeled by in utero electroporation of the lateral ventricular zone migrated into the LCS, and entered the lateral neocortex, piriform cortex and amygdala, where they differentiated primarily as pyramidal neurons. RNAi of DCX or LIS1 disrupted migration into amygdala and piriform cortex and caused many neurons to accumulate in the external and amygdalar capsules. RNAi of LIS1 and DCX had similar as well as distinguishable effects on the pattern of altered migration. Combinatorial RNAi of LIS1 and DCX further suggested interaction in the functions of LIS1 and DCX on the morphology and migration of migrating neurons in the LCS. Together, these results confirm that the LCS contributes pyramidal neurons to ventral forebrain structures and reveals that DCX and LIS1 have important functions in this major migratory pathway in the developing forebrain.}, Author = {Bai, Jilin and Ramos, Raddy L and Paramasivam, Murugan and Siddiqi, Faez and Ackman, James B and LoTurco, Joseph J}, Date-Added = {2014-06-23 18:26:21 +0000}, Date-Modified = {2014-06-23 18:26:21 +0000}, Doi = {10.1159/000109859}, Journal = {Dev Neurosci}, Journal-Full = {Developmental neuroscience}, Mesh = {Amygdala; Animals; Cell Differentiation; Cell Movement; Electroporation; Female; Gene Expression Regulation, Developmental; Microtubule-Associated Proteins; Nerve Tissue Proteins; Neural Pathways; Neuropeptides; Olfactory Pathways; Prosencephalon; Pyramidal Cells; RNA Interference; Rats; Rats, Wistar; Stem Cells}, Number = {1-3}, Pages = {144-56}, pmid = {18075262}, Pst = {ppublish}, Title = {The role of DCX and LIS1 in migration through the lateral cortical stream of developing forebrain}, Volume = {30}, Year = {2008}, url = {papers/Bai_DevNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000109859}} @article{Golding:2014, Abstract = {Inhibitory interneurons (INs) critically control the excitability and plasticity of neuronal networks, but whether activity can direct INs into specific circuits during development is unknown. Here, we report that in the dorsal lateral geniculate nucleus (dLGN), which relays retinal input to the cortex, circuit activity is required for the migration, molecular differentiation, and functional integration of INs. We first characterize the prenatal origin and molecular identity of dLGN INs, revealing their recruitment from an Otx2(+) neuronal pool located in the adjacent ventral LGN. Using time-lapse and electrophysiological recordings, together with genetic and pharmacological perturbation of retinal waves, we show that retinal activity directs the navigation and circuit incorporation of dLGN INs during the first postnatal week, thereby regulating the inhibition of thalamocortical circuits. These findings identify an input-dependent mechanism regulating IN migration and circuit inhibition, which may account for the progressive recruitment of INs into expanding excitatory circuits during evolution.}, Author = {Golding, Bruno and Pouchelon, Gabrielle and Bellone, Camilla and Murthy, Sahana and Di Nardo, Ariel A and Govindan, Subashika and Ogawa, Masahuro and Shimogori, Tomomi and L{\"u}scher, Christian and Dayer, Alexandre and Jabaudon, Denis}, Date-Added = {2014-04-08 16:06:10 +0000}, Date-Modified = {2014-04-08 16:06:10 +0000}, Doi = {10.1016/j.neuron.2014.01.032}, Journal = {Neuron}, Journal-Full = {Neuron}, Month = {Mar}, Number = {5}, Pages = {1057-69}, pmid = {24607228}, Pst = {ppublish}, Title = {Retinal input directs the recruitment of inhibitory interneurons into thalamic visual circuits}, Volume = {81}, Year = {2014}, url = {papers/Golding_Neuron2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2014.01.032}} @article{Chen:2013a, Abstract = {Fluorescent calcium sensors are widely used to image neural activity. Using structure-based mutagenesis and neuron-based screening, we developed a family of ultrasensitive protein calcium sensors (GCaMP6) that outperformed other sensors in cultured neurons and in zebrafish, flies and mice in vivo. In layer 2/3 pyramidal neurons of the mouse visual cortex, GCaMP6 reliably detected single action potentials in neuronal somata and orientation-tuned synaptic calcium transients in individual dendritic spines. The orientation tuning of structurally persistent spines was largely stable over timescales of weeks. Orientation tuning averaged across spine populations predicted the tuning of their parent cell. Although the somata of GABAergic neurons showed little orientation tuning, their dendrites included highly tuned dendritic segments (5-40-µm long). GCaMP6 sensors thus provide new windows into the organization and dynamics of neural circuits over multiple spatial and temporal scales.}, Author = {Chen, Tsai-Wen and Wardill, Trevor J and Sun, Yi and Pulver, Stefan R and Renninger, Sabine L and Baohan, Amy and Schreiter, Eric R and Kerr, Rex A and Orger, Michael B and Jayaraman, Vivek and Looger, Loren L and Svoboda, Karel and Kim, Douglas S}, Date-Added = {2014-03-28 15:24:26 +0000}, Date-Modified = {2014-03-28 15:25:08 +0000}, Doi = {10.1038/nature12354}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {technique; Methods; gene; calcium imaging; in vivo; Mouse; optical physiology}, Mesh = {Action Potentials; Animals; Calcium; Calcium-Binding Proteins; Cells, Cultured; Dendritic Spines; Fluorescent Dyes; GABAergic Neurons; Luminescent Proteins; Mice; Molecular Imaging; Mutagenesis; Protein Engineering; Pyramidal Cells; Visual Cortex}, Month = {Jul}, Number = {7458}, Pages = {295-300}, Pmc = {PMC3777791}, pmid = {23868258}, Pst = {ppublish}, Title = {Ultrasensitive fluorescent proteins for imaging neuronal activity}, Volume = {499}, Year = {2013}, url = {papers/Chen_Nature2013a.pdf}} @article{Zingg:2014, Abstract = {Numerous studies have examined the neuronal inputs and outputs of many areas within the mammalian cerebral cortex, but how these areas are organized into neural networks that communicate across the entire cortex is unclear. Over 600 labeled neuronal pathways acquired from tracer injections placed across the entire mouse neocortex enabled us to generate a cortical connectivity atlas. A total of 240 intracortical connections were manually reconstructed within a common neuroanatomic framework, forming a cortico-cortical connectivity map that facilitates comparison of connections from different cortical targets. Connectivity matrices were generated to provide an overview of all intracortical connections and subnetwork clusterings. The connectivity matrices and cortical map revealed that the entire cortex is organized into four somatic sensorimotor, two medial, and two lateral subnetworks that display unique topologies and can interact through select cortical areas. Together, these data provide a resource that can be used to further investigate cortical networks and their corresponding functions.}, Author = {Zingg, Brian and Hintiryan, Houri and Gou, Lin and Song, Monica Y and Bay, Maxwell and Bienkowski, Michael S and Foster, Nicholas N and Yamashita, Seita and Bowman, Ian and Toga, Arthur W and Dong, Hong-Wei}, Date-Added = {2014-03-18 00:58:16 +0000}, Date-Modified = {2014-03-18 00:58:16 +0000}, Doi = {10.1016/j.cell.2014.02.023}, Journal = {Cell}, Journal-Full = {Cell}, Month = {Feb}, Number = {5}, Pages = {1096-111}, pmid = {24581503}, Pst = {ppublish}, Title = {Neural networks of the mouse neocortex}, Volume = {156}, Year = {2014}, url = {papers/Zingg_Cell2014a.pdf}, Bdsk-File-2 = {papers/Zingg_Cell2014b.pdf}, Bdsk-File-3 = {papers/Zingg_Cell2014.xlsx}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2014.02.023}} @article{Rash:2011, Abstract = {The processes regulating cortical surface area expansion during development and evolution are unknown. We show that loss of function of all fibroblast growth factor receptors (FgfRs) expressed at the earliest stages of cortical development causes severe deficits in surface area growth by embryonic day 12.5 (E12.5) in the mouse. In FgfR mutants, accelerated production of neurons led to severe loss of radial progenitors and premature termination of neurogenesis. Nevertheless, these mutants showed remarkably little change in cortical layer structure. Birth-dating experiments indicated that a greater proportion of layer fates was generated during early neurogenic stages, revealing that FgfR activity normally slows the temporal progression of cortical layer fates. Electroporation of a dominant-negative FgfR at E11.5 increased cortical neurogenesis in normal mice--an effect that was blocked by simultaneous activation of the Notch pathway. Together with changes in the expression of Notch pathway genes in FgfR mutant embryos, these findings indicate that Notch lies downstream of FgfR signaling in the same pathway regulating cortical neurogenesis and begin to establish a mechanism for regulating cortical surface expansion.}, Author = {Rash, Brian G and Lim, H David and Breunig, Joshua J and Vaccarino, Flora M}, Date-Added = {2014-02-28 19:42:16 +0000}, Date-Modified = {2014-02-28 19:44:58 +0000}, Doi = {10.1523/JNEUROSCI.4439-11.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; Cerebral Cortex; Neocortex; radial glia; neurogenesis; Mouse}, Mesh = {Age Factors; Analysis of Variance; Animals; Brain; Bromodeoxyuridine; Caspase 3; Cell Count; Cell Differentiation; Cells, Cultured; Cerebral Cortex; DNA-Binding Proteins; Electroporation; Embryo, Mammalian; Eye Proteins; Fatty Acid-Binding Proteins; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Homeodomain Proteins; Ki-67 Antigen; Mice; Mice, Transgenic; Mutation; Nerve Tissue Proteins; Neurogenesis; Neurons; Paired Box Transcription Factors; Receptors, Fibroblast Growth Factor; Receptors, Notch; Repressor Proteins; Signal Transduction; Stem Cells; T-Box Domain Proteins; Transcription Factors}, Month = {Oct}, Number = {43}, Pages = {15604-17}, Pmc = {PMC3235689}, pmid = {22031906}, Pst = {ppublish}, Title = {FGF signaling expands embryonic cortical surface area by regulating Notch-dependent neurogenesis}, Volume = {31}, Year = {2011}, url = {papers/Rash_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4439-11.2011}} @article{Rash:2013, Abstract = {Gyrification allows an expanded cortex with greater functionality to fit into a smaller cranium. However, the mechanisms of gyrus formation have been elusive. We show that ventricular injection of FGF2 protein at embryonic day 11.5-before neurogenesis and before the formation of intrahemispheric axonal connections-altered the overall size and shape of the cortex and induced the formation of prominent, bilateral gyri and sulci in the rostrolateral neocortex. We show increased tangential growth of the rostral ventricular zone (VZ) but decreased Wnt3a and Lef1 expression in the cortical hem and adjacent hippocampal promordium and consequent impaired growth of the caudal cortical primordium, including the hippocampus. At the same time, we observed ectopic Er81 expression, increased proliferation of Tbr2-expressing (Tbr2(+)) intermediate neuronal progenitors (INPs), and elevated Tbr1(+) neurogenesis in the regions that undergo gyrification, indicating region-specific actions of FGF2 on the VZ and subventricular zone (SVZ). However, the relative number of basal radial glia-recently proposed to be important in gyrification-appeared to be unchanged. These findings are consistent with the hypothesis that increased radial unit production together with rapid SVZ growth and heightened localized neurogenesis can cause cortical gyrification in lissencephalic species. These data also suggest that the position of cortical gyri can be molecularly specified in mice. In contrast, a different ligand, FGF8b, elicited surface area expansion throughout the cortical primordium but no gyrification. Our findings demonstrate that individual members of the diverse Fgf gene family differentially regulate global as well as regional cortical growth rates while maintaining cortical layer structure.}, Author = {Rash, Brian G and Tomasi, Simone and Lim, H David and Suh, Carol Y and Vaccarino, Flora M}, Date-Added = {2014-02-28 19:33:06 +0000}, Date-Modified = {2014-02-28 19:34:43 +0000}, Doi = {10.1523/JNEUROSCI.3621-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; Cerebral Cortex; Neocortex; Mouse; radial glia; neurogenesis}, Mesh = {Animals; Antimetabolites; Axons; Brain Chemistry; Bromodeoxyuridine; Cell Count; Cerebral Cortex; Cerebral Ventricles; DNA, Complementary; Densitometry; Dependovirus; Female; Fibroblast Growth Factor 2; Green Fluorescent Proteins; Immunohistochemistry; In Situ Hybridization; Lymphoid Enhancer-Binding Factor 1; Mice; Neocortex; Pregnancy; RNA; Real-Time Polymerase Chain Reaction; Wnt3A Protein}, Month = {Jun}, Number = {26}, Pages = {10802-14}, Pmc = {PMC3693057}, pmid = {23804101}, Pst = {ppublish}, Title = {Cortical gyrification induced by fibroblast growth factor 2 in the mouse brain}, Volume = {33}, Year = {2013}, url = {papers/Rash_JNeurosci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3621-12.2013}} @article{Shitamukai:2011, Abstract = {Radial glia cells function as neural stem cells in the developing brain and generate self-renewing and differentiating daughter cells by asymmetric cell divisions. During these divisions, the apical process or basal process of the elongated epithelial structure is asymmetrically partitioned into daughter cells, depending on developmental contexts. However, in mammalian neurogenesis, the relationship between these subcellular structures and self-renewability is largely unknown. We induced oblique cleavages of radial glia cells to split the apical and basal processes into two daughters, and investigated the fate and morphology of the daughters in slice cultures. We observed that the more basal daughter cell that inherits the basal process self-renews outside of the ventricular zone (VZ), while the more apical daughter cell differentiates. These self-renewing progenitors, termed "outer VZ progenitors," retain the basal but not the apical process, as recently reported for the outer subventricular zone (OSVZ) progenitors in primates (Fietz et al., 2010; Hansen et al., 2010); to self-renew, they require clonal Notch signaling between sibling cells. We also found a small endogenous population of outer VZ progenitors in the mouse embryonic neocortex, consistent with a low frequency of oblique radial glia divisions. Our results describe the general role of the basal process in the self-renewal of neural progenitors and implicate the loss of the apical junctions during oblique divisions as a possible mechanism for generating OSVZ progenitors. We propose that mouse outer VZ progenitors, induced by oblique cleavages, provide a model to study both progenitor self-renewal and OSVZ progenitors.}, Author = {Shitamukai, Atsunori and Konno, Daijiro and Matsuzaki, Fumio}, Date-Added = {2014-02-28 19:30:03 +0000}, Date-Modified = {2014-02-28 19:31:20 +0000}, Doi = {10.1523/JNEUROSCI.4773-10.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; radial glia; cortical columns; Cerebral Cortex; Neocortex}, Mesh = {Analysis of Variance; Animals; Cell Differentiation; Cell Lineage; Cells, Cultured; Immunohistochemistry; Mice; Mice, Inbred ICR; Neocortex; Neuroglia; Neurons; Stem Cells}, Month = {Mar}, Number = {10}, Pages = {3683-95}, pmid = {21389223}, Pst = {ppublish}, Title = {Oblique radial glial divisions in the developing mouse neocortex induce self-renewing progenitors outside the germinal zone that resemble primate outer subventricular zone progenitors}, Volume = {31}, Year = {2011}, url = {papers/Shitamukai_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4773-10.2011}} @article{Blumberg:2013a, Abstract = {BACKGROUND: During active (or REM) sleep, infant mammals exhibit myoclonic twitches of skeletal muscles throughout the body, generating jerky, discrete movements of the distal limbs. Hundreds of thousands of limb twitches are produced daily, and sensory feedback from these movements is a substantial driver of infant brain activity, suggesting that they contribute to motor learning and sensorimotor integration. It is not known whether the production of twitches is random or spatiotemporally structured, or whether the patterning of twitching changes with age; such information is critical for understanding how twitches contribute to development. RESULTS: We used high-speed videography and 3D motion tracking to assess the spatiotemporal structure of twitching at forelimb joints in 2- and 8-day-old rats. At both ages, twitches exhibited highly structured spatiotemporal properties at multiple timescales, including synergistic and multijoint movements within and across forelimbs. Hierarchical cluster analysis and latent class analysis revealed developmental changes in twitching quantity and patterning. Critically, we found evidence for a selectionist process whereby movement patterns at the early age compete for retention and expression over development. CONCLUSIONS: These findings indicate that twitches are not produced randomly but are highly structured at multiple timescales. This structure has important implications for understanding brain and spinal mechanisms that produce twitching, and the role that sensory feedback from twitching plays in sensorimotor system development. We propose that twitches represent a heretofore-overlooked form of motor exploration that helps animals probe the biomechanics of their limbs, build motor synergies, and lay a foundation for complex, automatic, and goal-directed wake movements.}, Author = {Blumberg, Mark S and Coleman, Cassandra M and Gerth, Ashlynn I and McMurray, Bob}, Date-Added = {2014-02-25 21:00:07 +0000}, Date-Modified = {2014-02-25 21:01:55 +0000}, Doi = {10.1016/j.cub.2013.08.055}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {development; Rats; sleep; sensory-motor; spontaneous activity;}, Month = {Nov}, Number = {21}, Pages = {2100-9}, Pmc = {PMC3823644}, pmid = {24139739}, Pst = {ppublish}, Title = {Spatiotemporal structure of REM sleep twitching reveals developmental origins of motor synergies}, Volume = {23}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2013.08.055}} @article{Blumberg:2013, Abstract = {It is still not known how the 'rudimentary' movements of fetuses and infants are transformed into the coordinated, flexible and adaptive movements of adults. In addressing this important issue, we consider a behavior that has been perennially viewed as a functionless by-product of a dreaming brain: the jerky limb movements called myoclonic twitches. Recent work has identified the neural mechanisms that produce twitching as well as those that convey sensory feedback from twitching limbs to the spinal cord and brain. In turn, these mechanistic insights have helped inspire new ideas about the functional roles that twitching might play in the self-organization of spinal and supraspinal sensorimotor circuits. Striking support for these ideas is coming from the field of developmental robotics: when twitches are mimicked in robot models of the musculoskeletal system, the basic neural circuitry undergoes self-organization. Mutually inspired biological and synthetic approaches promise not only to produce better robots, but also to solve fundamental problems concerning the developmental origins of sensorimotor maps in the spinal cord and brain.}, Author = {Blumberg, Mark S and Marques, Hugo Gravato and Iida, Fumiya}, Date-Added = {2014-02-25 20:59:56 +0000}, Date-Modified = {2014-02-25 21:01:33 +0000}, Doi = {10.1016/j.cub.2013.04.075}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {toread; development; Rats; sleep; sensory-motor; spontaneous activity; review; wholeBrain}, Mesh = {Animals; Brain; Feedback, Sensory; Fetal Movement; Humans; Motor Activity; Movement; Musculoskeletal Development; Rats; Robotics; Sleep; Spinal Cord}, Month = {Jun}, Number = {12}, Pages = {R532-7}, Pmc = {PMC3709969}, pmid = {23787051}, Pst = {ppublish}, Title = {Twitching in sensorimotor development from sleeping rats to robots}, Volume = {23}, Year = {2013}, url = {papers/Blumberg_CurrBiol2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2013.04.075}} @article{Ackman:2014, Abstract = {The initial structural and functional development of visual circuits in reptiles, birds, and mammals happens independent of sensory experience. After eye opening, visual experience further refines and elaborates circuits that are critical for normal visual function. Innate genetic programs that code for gradients of molecules provide gross positional information for developing nerve cells, yet much of the cytoarchitectural complexity and synaptogenesis of neurons depends on calcium influx, neurotransmitter release, and neural activity before the onset of vision. In fact, specific spatiotemporal patterns of neural activity, or 'retinal waves', emerge amidst the development of the earliest connections made between excitable cells in the developing eye. These patterns of spontaneous activity, which have been observed in all amniote retinae examined to date, may be an evolved adaptation for species with long gestational periods before the onset of functional vision, imparting an informational robustness and redundancy to guide development of visual maps across the nervous system. Recent experiments indicate that retinal waves play a crucial role in the development of interconnections between different parts of the visual system, suggesting that these spontaneous patterns serve as a template-matching mechanism to prepare higher-order visually associative circuits for the onset of visuomotor learning and behavior. Key questions for future studies include determining the exact sources and nature of spontaneous activity during development, characterizing the interactions between neural activity and transcriptional gene regulation, and understanding the extent of circuit connectivity governed by retinal waves within and between sensory-motor systems.}, Author = {Ackman, James B and Crair, Michael C}, Date-Added = {2014-02-25 20:58:36 +0000}, Date-Modified = {2014-02-25 20:58:36 +0000}, Doi = {10.1016/j.conb.2013.11.011}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Month = {Feb}, Pages = {166-175}, Pmc = {PMC3957181}, pmid = {24492092}, Pst = {ppublish}, Title = {Role of emergent neural activity in visual map development}, Volume = {24C}, Year = {2014}, url = {papers/Ackman_CurrOpinNeurobiol2014.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2013.11.011}} @article{Fogassi:2005, Abstract = {Inferior parietal lobule (IPL) neurons were studied when monkeys performed motor acts embedded in different actions and when they observed similar acts done by an experimenter. Most motor IPL neurons coding a specific act (e.g., grasping) showed markedly different activations when this act was part of different actions (e.g., for eating or for placing). Many motor IPL neurons also discharged during the observation of acts done by others. Most responded differentially when the same observed act was embedded in a specific action. These neurons fired during the observation of an act, before the beginning of the subsequent acts specifying the action. Thus, these neurons not only code the observed motor act but also allow the observer to understand the agent's intentions.}, Author = {Fogassi, Leonardo and Ferrari, Pier Francesco and Gesierich, Benno and Rozzi, Stefano and Chersi, Fabian and Rizzolatti, Giacomo}, Date-Added = {2014-01-29 16:00:24 +0000}, Date-Modified = {2014-01-29 16:00:58 +0000}, Doi = {10.1126/science.1106138}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {mirror neuron; mirror symmetry; learning; behavior; monkey; Posterior parietal cortex}, Mesh = {Animals; Comprehension; Electrophysiology; Food; Goals; Haplorhini; Intention; Microelectrodes; Motor Activity; Motor Cortex; Neurons; Parietal Lobe; Psychomotor Performance; Visual Perception}, Month = {Apr}, Number = {5722}, Pages = {662-7}, pmid = {15860620}, Pst = {ppublish}, Title = {Parietal lobe: from action organization to intention understanding}, Volume = {308}, Year = {2005}, url = {papers/Fogassi_Science2005.pdf}} @article{Hohl:2013, Abstract = {We have used a new approach to study the neural decoding function that converts the population response in extrastriate area MT into estimates of target motion to drive smooth pursuit eye movement. Experiments reveal significant trial-by-trial correlations between the responses of MT neurons and the initiation of pursuit. The preponderance of significant correlations and the relatively low reduction in noise between MT and the behavioral output support the hypothesis of a sensory origin for at least some of the trial-by-trial variation in pursuit initiation. The finding of mainly positive MT-pursuit correlations, whether the target speed is faster or slower than the neuron's preferred speed, places strong constraints on the neural decoding computation. We propose that decoding is based on normalizing a weighted population vector of opponent motion responses; normalization comes from neurons uncorrelated with those used to compute the weighted population vector.}, Author = {Hohl, Sonja S and Chaisanguanthum, Kris S and Lisberger, Stephen G}, Date-Added = {2014-01-29 15:38:49 +0000}, Date-Modified = {2014-01-29 15:39:41 +0000}, Doi = {10.1016/j.neuron.2013.05.026}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Eye Movements; Saccades; monkey; sensory-motor; visual system; function; behavior}, Mesh = {Action Potentials; Animals; Eye Movements; Macaca mulatta; Male; Models, Neurological; Motion Perception; Neurons; Photic Stimulation; Pursuit, Smooth; Reaction Time; Visual Cortex}, Month = {Jul}, Number = {1}, Pages = {167-79}, Pmc = {PMC3757094}, pmid = {23849202}, Pst = {ppublish}, Title = {Sensory population decoding for visually guided movements}, Volume = {79}, Year = {2013}, url = {papers/Hohl_Neuron2013.pdf}, Bdsk-File-2 = {papers/Hohl_Neuron2013a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.05.026}} @article{Lee:2013, Abstract = {Sensory inputs control motor behavior with a strength, or gain, that can be modulated according to the movement conditions. In smooth pursuit eye movements, the response to a brief perturbation of target motion is larger during pursuit of a moving target than during fixation of a stationary target. As a step toward identifying the locus and mechanism of gain modulation, we test whether it acts on signals that are in visual or motor coordinates. Monkeys tracked targets that moved at 15$\,^{\circ}$/s in one of eight directions, including left, right, up, down, and the four oblique directions. In eight-ninths of the trials, the target underwent a brief perturbation that consisted of a single cycle of a 10 Hz sine wave of amplitude $\pm$5$\,^{\circ}$/s in one of the same eight directions. Even for oblique directions of baseline target motion, the magnitude of the eye velocity response to the perturbation was largest for a perturbation near the axis of target motion and smallest for a perturbation along the orthogonal axis. Computational modeling reveals that our data are reproduced when the strength of visual-motor transmission is modulated in sensory coordinates, and there is a static motor bias that favors horizontal eye movements. A network model shows how the output from the smooth eye movement region of the frontal eye fields (FEF(SEM)) could implement gain control by shifting the peak of a visual population response along the axes of preferred image speed and direction.}, Author = {Lee, Joonyeol and Yang, Jin and Lisberger, Stephen G}, Date-Added = {2014-01-29 15:35:25 +0000}, Date-Modified = {2014-01-29 15:35:38 +0000}, Doi = {10.1523/JNEUROSCI.4846-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {sensory-motor; Eye Movements; Saccades; monkey; visual system; function; behavior; Cerebellum}, Mesh = {Algorithms; Animals; Data Interpretation, Statistical; Functional Laterality; Haplorhini; Individuality; Male; Models, Neurological; Movement; Nerve Net; Normal Distribution; Parietal Lobe; Photic Stimulation; Psychomotor Performance; Pursuit, Smooth; Retina; Synaptic Transmission; Visual Pathways; Visual Perception}, Month = {May}, Number = {22}, Pages = {9420-30}, Pmc = {PMC3705569}, pmid = {23719810}, Pst = {ppublish}, Title = {Control of the gain of visual-motor transmission occurs in visual coordinates for smooth pursuit eye movements}, Volume = {33}, Year = {2013}, url = {papers/Lee_JNeurosci2013.pdf}} @article{Lisberger:2010, Abstract = {Smooth-pursuit eye movements transform 100 ms of visual motion into a rapid initiation of smooth eye movement followed by sustained accurate tracking. Both the mean and variation of the visually driven pursuit response can be accounted for by the combination of the mean tuning curves and the correlated noise within the sensory representation of visual motion in extrastriate visual area MT. Sensory-motor and motor circuits have both housekeeping and modulatory functions, implemented in the cerebellum and the smooth eye movement region of the frontal eye fields. The representation of pursuit is quite different in these two regions of the brain, but both regions seem to control pursuit directly with little or no noise added downstream. Finally, pursuit exhibits a number of voluntary characteristics that happen on short timescales. These features make pursuit an excellent exemplar for understanding the general properties of sensory-motor processing in the brain.}, Author = {Lisberger, Stephen G}, Date-Added = {2014-01-29 15:32:09 +0000}, Date-Modified = {2014-01-29 15:33:14 +0000}, Doi = {10.1016/j.neuron.2010.03.027}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {sensory-motor; Eye Movements; Saccades; monkey; visual system; review literature; function; behavior; Cerebellum}, Mesh = {Animals; Eye Movements; Humans; Motion Perception; Photic Stimulation; Pursuit, Smooth; Visual Pathways}, Month = {May}, Number = {4}, Pages = {477-91}, Pmc = {PMC2887486}, pmid = {20510853}, Pst = {ppublish}, Title = {Visual guidance of smooth-pursuit eye movements: sensation, action, and what happens in between}, Volume = {66}, Year = {2010}, url = {papers/Lisberger_Neuron2010.pdf}} @article{Oertel-Knochel:2011, Abstract = {The hemispheres of the human brain are anatomically and functionally asymmetric, and many cognitive and motor functions such as language and handedness are lateralized. This review examines anatomical, psychological, and physiological approaches to the understanding of separate hemispheric functions and their integration. The concept of hemispheric laterality plays a central role in current neuropsychological and pathophysiological models of schizophrenia. Reduced hemispheric asymmetry has also been reported for other mental disorders, for example, bipolar disorder. Recent research reflects an increasing interest in the molecular and population genetics of laterality and its potential link with animal models of schizophrenia. The authors review the principles of laterality and brain asymmetry and discuss the evidence for changes in asymmetry in schizophrenia and other mental disorders.}, Author = {Oertel-Kn{\"o}chel, Viola and Linden, David E J}, Date-Added = {2014-01-28 02:34:55 +0000}, Date-Modified = {2014-01-28 13:43:48 +0000}, Doi = {10.1177/1073858410386493}, Journal = {Neuroscientist}, Journal-Full = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, Keywords = {Schizophrenia; review literature; human; neurological disorder; Genetic; Functional Laterality; lateralization; mirror symmetry; hemisphere}, Mesh = {Animals; Cerebrum; Functional Laterality; Humans; Schizophrenia}, Month = {Oct}, Number = {5}, Pages = {456-67}, pmid = {21518811}, Pst = {ppublish}, Title = {Cerebral asymmetry in schizophrenia}, Volume = {17}, Year = {2011}, url = {papers/Oertel-Knöchel_Neuroscientist2011.pdf}} @article{Dragovic:2005, Abstract = {OBJECTIVE: The prevalence of various anomalous handedness subtypes in schizophrenia patients remains ambiguous. Although current literature favours the notion that the shift in lateral preferences seen is because of an increase of mixed-handedness, several studies suggest that exclusive left handedness is more prevalent than in the general population. METHOD: Over 40 studies with reported prevalence data on various handedness subtypes in a schizophrenia population were evaluated by meta-analysis. Combined odds ratios for the three common handedness subtypes (left, mixed, and right) were separately calculated. RESULTS: Each of the three atypical hand dominance patterns were significantly greater in schizophrenia patients than in control subjects, showing that the leftward shift in handedness distribution is not entirely because of an increase in mixed-handedness alone. CONCLUSION: An increase of exclusive left-handedness is at variance with the prevailing assertion that the handedness shift in schizophrenia patients is because of a diffuse and bilateral hemispheric insult.}, Author = {Dragovic, M and Hammond, G}, Date-Added = {2014-01-27 21:07:13 +0000}, Date-Modified = {2014-01-27 21:08:09 +0000}, Doi = {10.1111/j.1600-0447.2005.00519.x}, Journal = {Acta Psychiatr Scand}, Journal-Full = {Acta psychiatrica Scandinavica}, Keywords = {Functional Laterality; lateralization; handedness; Schizophrenia; behavior; Human; review literature}, Mesh = {Functional Laterality; Humans; Psychiatric Status Rating Scales; Schizophrenia}, Month = {Jun}, Number = {6}, Pages = {410-9}, pmid = {15877707}, Pst = {ppublish}, Title = {Handedness in schizophrenia: a quantitative review of evidence}, Volume = {111}, Year = {2005}, url = {papers/Dragovic_ActaPsychiatrScand2005.pdf}} @article{Sommer:2001, Abstract = {BACKGROUND: Cerebral lateralisation appears to be decreased in schizophrenia. Results of studies investigating this, however, are equivocal. AIMS: To review quantitatively the literature on decreased lateralisation in schizophrenia. METHOD: Meta-analyses were conducted on 19 studies on handedness, 10 dichotic listening studies and 39 studies investigating anatomical asymmetry in schizophrenia. RESULTS: The prevalence of mixed- and left-handedness ('non-right-handedness') was significantly higher in patients with schizophrenia as compared to healthy controls, and also as compared to psychiatric controls. The analysis of dichotic listening studies revealed no significant difference in lateralisation in schizophrenia. However, when analysis was restricted to studies using consonant-vowel or fused word tasks, significantly decreased lateralisation in schizophrenia emerged. Asymmetry of the planum temporale and the Sylvian fissure was significantly decreased in schizophrenia, while asymmetry of the temporal horn of the lateral ventricle was not. CONCLUSION: Strong evidence is provided for decreased cerebral lateralisation in schizophrenia.}, Author = {Sommer, I and Ramsey, N and Kahn, R and Aleman, A and Bouma, A}, Date-Added = {2014-01-27 20:45:24 +0000}, Date-Modified = {2014-01-27 21:02:27 +0000}, Journal = {Br J Psychiatry}, Journal-Full = {The British journal of psychiatry : the journal of mental science}, Keywords = {Grants; Schizophrenia; Functional Laterality; lateralization; Cerebral Cortex; behavior; handedness; Human; review literature; wholeBrain}, Mesh = {Brain; Dichotic Listening Tests; Functional Laterality; Humans; Schizophrenia; Schizophrenic Psychology; Speech Perception}, Month = {Apr}, Pages = {344-51}, pmid = {11282814}, Pst = {ppublish}, Title = {Handedness, language lateralisation and anatomical asymmetry in schizophrenia: meta-analysis}, Volume = {178}, Year = {2001}, url = {papers/Sommer_BrJPsychiatry2001.pdf}} @article{Crawley:2008a, Abstract = {Comprehensive behavioral analyses of transgenic and knockout mice have successfully identified the functional roles of many genes in the brain. Over the past 10 years, strategies for mouse behavioral phenotyping have evolved to maximize the scope and replicability of findings from a cohort of mutant mice, minimize the interpretation of procedural artifacts, and provide robust translational tools to test hypotheses and develop treatments. This Primer addresses experimental design issues and offers examples of high-throughput batteries, learning and memory tasks, and anxiety-related tests.}, Author = {Crawley, Jacqueline N}, Date-Added = {2014-01-27 20:08:27 +0000}, Date-Modified = {2014-01-27 20:10:12 +0000}, Doi = {10.1016/j.neuron.2008.03.001}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Mice, Neurologic Mutants;Behavior, Animal;Female;Phenotype;research support, n.i.h., intramural;Animals;Disease Models, Animal;Male;review;Mice; Schizophrenia; Methods; wholeBrain}, Mesh = {Animals; Behavior, Animal; Disease Models, Animal; Female; Male; Mice; Mice, Neurologic Mutants; Phenotype}, Month = {Mar}, Number = {6}, Pages = {809-18}, pmid = {18367082}, Pst = {ppublish}, Title = {Behavioral phenotyping strategies for mutant mice}, Volume = {57}, Year = {2008}, url = {papers/Crawley_Neuron2008a.pdf}} @article{Crawley:1999, Abstract = {Rigorous experimental design can minimize the high risk of false positives and false negatives in the behavioral phenotyping of a new transgenic or knockout mouse. Use of well established, quantitative, reproducible behavioral tasks, appropriate Ns, correct statistical methods, consideration of background genes contributed by the parental strains, and attention to litter and gender issues, will maximize meaningful comparisons of -/-, +/-, and +/+ genotypes. Strategies developed and used by our laboratory are described in this review. Preliminary observations evaluate general health and neurological reflexes. Sensory abilities and motor functions are extensively quantitated. Specific tests include observations of home cage behaviors, body weight, body temperature, appearance of the fur and whiskers, righting reflex, acoustic startle, eye blink, pupil constriction, vibrissae reflex, pinna reflex, Digiscan open field locomotion, rotarod motor coordination, hanging wire, footprint pathway, visual cliff, auditory threshold, pain threshold, and olfactory acuity. Hypothesis testing then focuses on at least three well-validated tasks within each relevant behavioral domain. Specific tests for mice are described herein for the domains of learning and memory, feeding, nociception, and behaviors relevant to discrete symptoms of human anxiety, depression, schizophrenia, and drug addiction. An example of our approach is illustrated in the behavioral phenotyping of C/EBPdelta knockout mice, which appear to be normal on general health, neurological reflexes, sensory and motor tasks, and the Morris water task, but show remarkably enhanced performance on contextual fear conditioning.}, Author = {Crawley, J N}, Date-Added = {2014-01-27 20:04:38 +0000}, Date-Modified = {2014-01-27 20:05:48 +0000}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {mouse; mice; behavior; Phenotype; Schizophrenia; Methods; review literature; Grants; wholeBrain}, Mesh = {Animals; Behavior, Animal; Health; Humans; Mice; Mice, Knockout; Mice, Transgenic; Phenotype; Psychomotor Performance; Research Design; Sensation}, Month = {Jul}, Number = {1}, Pages = {18-26}, pmid = {10448192}, Pst = {ppublish}, Title = {Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests}, Volume = {835}, Year = {1999}, url = {papers/Crawley_BrainRes1999.pdf}} @article{Pletnikov:2008, Abstract = {A strong candidate gene for schizophrenia and major mental disorders, disrupted-in-schizophrenia 1 (DISC1) was first described in a large Scottish family in which a balanced chromosomal translocation segregates with schizophrenia and other psychiatric illnesses. The translocation mutation may result in loss of DISC1 function via haploinsufficiency or dominant-negative effects of a predicted mutant DISC1 truncated protein product. DISC1 has been implicated in neurodevelopment, including maturation of the cerebral cortex. To evaluate the neuronal and behavioral effects of mutant DISC1, the Tet-off system under the regulation of the CAMKII promoter was used to generate transgenic mice with inducible expression of mutant human DISC1 (hDISC1) limited to forebrain regions, including cerebral cortex, hippocampus and striatum. Expression of mutant hDISC1 was not associated with gross neurodevelopmental abnormalities, but led to a mild enlargement of the lateral ventricles and attenuation of neurite outgrowth in primary cortical neurons. These morphological changes were associated with decreased protein levels of endogenous mouse DISC1, LIS1 and SNAP-25. Compared to their sex-matched littermate controls, mutant hDISC1 transgenic male mice exhibited spontaneous hyperactivity in the open field and alterations in social interaction, and transgenic female mice showed deficient spatial memory. The results show that the neuronal and behavioral effects of mutant hDISC1 are consistent with a dominant-negative mechanism, and are similar to some features of schizophrenia. The present mouse model may facilitate the study of aspects of the pathogenesis of schizophrenia.}, Author = {Pletnikov, M V and Ayhan, Y and Nikolskaia, O and Xu, Y and Ovanesov, M V and Huang, H and Mori, S and Moran, T H and Ross, C A}, Date-Added = {2014-01-27 19:54:14 +0000}, Date-Modified = {2014-01-27 19:54:44 +0000}, Doi = {10.1038/sj.mp.4002079}, Journal = {Mol Psychiatry}, Journal-Full = {Molecular psychiatry}, Keywords = {Schizophrenia; Grants; behavior; gene; mice; Mouse}, Mesh = {Animals; Animals, Newborn; Behavior, Animal; Behavioral Symptoms; Brain; Disease Models, Animal; Female; Gene Expression Regulation, Developmental; Humans; Lateral Ventricles; Male; Mice; Mice, Transgenic; Molecular Weight; Mutation; Nerve Tissue Proteins; Schizophrenia}, Month = {Feb}, Number = {2}, Pages = {173-86, 115}, pmid = {17848917}, Pst = {ppublish}, Title = {Inducible expression of mutant human DISC1 in mice is associated with brain and behavioral abnormalities reminiscent of schizophrenia}, Volume = {13}, Year = {2008}, url = {papers/Pletnikov_MolPsychiatry2008.pdf}} @article{Carandini:2013, Abstract = {The study of perceptual decision-making offers insight into how the brain uses complex, sometimes ambiguous information to guide actions. Understanding the underlying processes and their neural bases requires that one pair recordings and manipulations of neural activity with rigorous psychophysics. Though this research has been traditionally performed in primates, it seems increasingly promising to pursue it at least partly in mice and rats. However, rigorous psychophysical methods are not yet as developed for these rodents as they are for primates. Here we give a brief overview of the sensory capabilities of rodents and of their cortical areas devoted to sensation and decision. We then review methods of psychophysics, focusing on the technical issues that arise in their implementation in rodents. These methods represent a rich set of challenges and opportunities.}, Author = {Carandini, Matteo and Churchland, Anne K}, Date-Added = {2014-01-27 16:03:56 +0000}, Date-Modified = {2014-01-27 16:04:47 +0000}, Doi = {10.1038/nn.3410}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {mouse; behavior; Functional Laterality; Decision Making; Grants; wholeBrain; Schizophrenia; Methods; review literature; Psychophysics}, Mesh = {Animals; Brain; Decision Making; Mice; Neural Pathways; Neurons; Perception; Physical Stimulation; Psychophysics; Rats; Signal Detection, Psychological}, Month = {Jul}, Number = {7}, Pages = {824-31}, pmid = {23799475}, Pst = {ppublish}, Title = {Probing perceptual decisions in rodents}, Volume = {16}, Year = {2013}, url = {papers/Carandini_NatNeurosci2013.pdf}} @article{Jia:2013, Abstract = {Our ability to control complex systems is a fundamental challenge of contemporary science. Recently introduced tools to identify the driver nodes, nodes through which we can achieve full control, predict the existence of multiple control configurations, prompting us to classify each node in a network based on their role in control. Accordingly a node is critical, intermittent or redundant if it acts as a driver node in all, some or none of the control configurations. Here we develop an analytical framework to identify the category of each node, leading to the discovery of two distinct control modes in complex systems: centralized versus distributed control. We predict the control mode for an arbitrary network and show that one can alter it through small structural perturbations. The uncovered bimodality has implications from network security to organizational research and offers new insights into the dynamics and control of complex systems.}, Author = {Jia, Tao and Liu, Yang-Yu and Cs{\'o}ka, Endre and P{\'o}sfai, M{\'a}rton and Slotine, Jean-Jacques and Barab{\'a}si, Albert-L{\'a}szl{\'o}}, Date-Added = {2014-01-15 14:33:31 +0000}, Date-Modified = {2014-01-15 14:34:03 +0000}, Doi = {10.1038/ncomms3002}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Keywords = {graph theory; Mathematics; models; self organization; network; Game Theory; Methods}, Pages = {2002}, pmid = {23774965}, Pst = {ppublish}, Title = {Emergence of bimodality in controlling complex networks}, Volume = {4}, Year = {2013}, url = {papers/Jia_NatCommun2013.pdf}} @article{Raj:2008, Abstract = {Gene expression is a fundamentally stochastic process, with randomness in transcription and translation leading to cell-to-cell variations in mRNA and protein levels. This variation appears in organisms ranging from microbes to metazoans, and its characteristics depend both on the biophysical parameters governing gene expression and on gene network structure. Stochastic gene expression has important consequences for cellular function, being beneficial in some contexts and harmful in others. These situations include the stress response, metabolism, development, the cell cycle, circadian rhythms, and aging.}, Author = {Raj, Arjun and van Oudenaarden, Alexander}, Date-Added = {2014-01-14 17:44:56 +0000}, Date-Modified = {2014-01-14 17:45:54 +0000}, Doi = {10.1016/j.cell.2008.09.050}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {handedness; gene; Gene Expression; development; Experimental; self organization; Selection (Genetics); Game Theory; asymmetry; lateralization}, Mesh = {Animals; Bacteria; Eukaryotic Cells; Gene Expression; Humans; Stochastic Processes; Transcription, Genetic}, Month = {Oct}, Number = {2}, Pages = {216-26}, Pmc = {PMC3118044}, pmid = {18957198}, Pst = {ppublish}, Title = {Nature, nurture, or chance: stochastic gene expression and its consequences}, Volume = {135}, Year = {2008}, url = {papers/Raj_Cell2008.pdf}} @article{Cai:2013, Abstract = {In the transgenic multicolor labeling strategy called 'Brainbow', Cre-loxP recombination is used to create a stochastic choice of expression among fluorescent proteins, resulting in the indelible marking of mouse neurons with multiple distinct colors. This method has been adapted to non-neuronal cells in mice and to neurons in fish and flies, but its full potential has yet to be realized in the mouse brain. Here we present several lines of mice that overcome limitations of the initial lines, and we report an adaptation of the method for use in adeno-associated viral vectors. We also provide technical advice about how best to image Brainbow-expressing tissue.}, Author = {Cai, Dawen and Cohen, Kimberly B and Luo, Tuanlian and Lichtman, Jeff W and Sanes, Joshua R}, Date-Added = {2014-01-08 21:07:08 +0000}, Date-Modified = {2014-01-08 21:07:08 +0000}, Doi = {10.1038/nmeth.2450}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Month = {May}, Number = {6}, Pages = {540-7}, Pmc = {PMC3713494}, pmid = {23817127}, Pst = {ppublish}, Title = {Improved tools for the Brainbow toolbox}, Volume = {10}, Year = {2013}, url = {papers/Cai_NatMethods2013.pdf}} @article{Kohl:2004, Abstract = {Fever is a common clinical complaint in adults and children with a variety of infectious illnesses, as well as a frequently reported adverse event following immunization. Although the level of measured temperature indicative of a "fever" was first defined in 1868, it remains unclear what role fever has as a physiologic reaction to invading substances, how best to measure body temperature and compare measurements from different body sites, and, consequently, how to interpret fever data derived from vaccine safety trials or immunization safety surveillance. However, even with many aspects of the societal, medical, economic, and epidemiologic meanings of fever as an adverse event following immunization (AEFI) still elusive, it is a generally benign--albeit common--clinical sign. By standardizing the definition and means of assessment of fever in vaccine safety studies, thereby permitting comparability of data, we hope to arrive at an improved understanding of its importance as an AEFI.}, Author = {Kohl, Katrin S and Marcy, S Michael and Blum, Michael and Connell Jones, Marcy and Dagan, Ron and Hansen, John and Nalin, David and Rothstein, Edward and {Brighton Collaboration Fever Working Group}}, Date-Added = {2013-12-12 17:13:47 +0000}, Date-Modified = {2013-12-12 17:14:10 +0000}, Doi = {10.1086/422454}, Journal = {Clin Infect Dis}, Journal-Full = {Clinical infectious diseases : an official publication of the Infectious Diseases Society of America}, Keywords = {health, child, infant, flu, influenza, vaccination, epilepsy, seizures}, Mesh = {Adult; Child; Fever; Humans; Infant; Seizures, Febrile; Vaccination}, Month = {Aug}, Number = {3}, Pages = {389-94}, pmid = {15307007}, Pst = {ppublish}, Title = {Fever after immunization: current concepts and improved future scientific understanding}, Volume = {39}, Year = {2004}, url = {papers/Kohl_ClinInfectDis2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1086/422454}} @article{Koplan:1979, Abstract = {Using decision analysis, we estimated the benefits, risks and costs of routine childhood immunization against pertussis. Without an immunization program, we predict that there would be a 71-fold increase in cases and an almost fourfold increase in deaths (2.0 to 7.6) per cohort of one million children. With a vaccination program, we predict 0.1 case of encephalitis associated with pertussis and five cases of post-vaccination encephalitis; without a program, there would be only 2.3 cases of encephalitis associated with pertussis. Community vaccination would reduce by 61 per cent the costs related to pertussis. Our analysis supports continuation of vaccination in routine childhood immunization programs, but suggests the need for more reliable data on complications from the vaccine, further study of the epidemiology of pertussis and development of a less toxic vaccine.}, Author = {Koplan, J P and Schoenbaum, S C and Weinstein, M C and Fraser, D W}, Date-Added = {2013-12-12 17:03:47 +0000}, Date-Modified = {2013-12-12 17:04:10 +0000}, Doi = {10.1056/NEJM197910253011703}, Journal = {N Engl J Med}, Journal-Full = {The New England journal of medicine}, Keywords = {health, child, infant, flu, influenza, vaccination, epilepsy, seizures}, Mesh = {Child; Child, Preschool; Cost-Benefit Analysis; Decision Theory; Encephalitis; Encephalomyelitis, Acute Disseminated; Europe; Humans; Infant; Infant, Newborn; Models, Theoretical; National Health Programs; Personal Health Services; Pertussis Vaccine; Risk; United States; Vaccination; Whooping Cough}, Month = {Oct}, Number = {17}, Pages = {906-11}, pmid = {39253}, Pst = {ppublish}, Title = {Pertussis vaccine--an analysis of benefits, risks and costs}, Volume = {301}, Year = {1979}, url = {papers/Koplan_NEnglJMed1979.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1056/NEJM197910253011703}} @article{Nelson:1976, Abstract = {We examined the frequency of development of afebrile seizures in 1706 children who had experienced at least one febrile seizure and were followed to the age of seven years. Epilepsy developed by seven years of age in 20 per 1000 (2 per cent), and another 10 per 1000 had at least one afebrile seizure that did not meet our definition of epilepsy. In children whose neurologic or developmental status was suspect or abnormal before any seizure and whose first seizure was complex (longer than 15 minutes, multiple or focal) epilepsy developed at a rate 18 times higher than in children with no febrile seizures (92 vs. 5 per 1000; P less than 0.001). In the largest group with febrile seizures, those previously normal with noncomplex first febrile seizures, epilepsy developed in 11 per 1000; this rate, although moderate, was greater than that for children with no febrile seizures (P = 0.027). Prior neurologic and developmental status and characteristics of the first febrile seizure are important predictors of epilepsy after febrile seizures.}, Author = {Nelson, K B and Ellenberg, J H}, Date-Added = {2013-12-12 16:30:41 +0000}, Date-Modified = {2013-12-12 16:30:55 +0000}, Doi = {10.1056/NEJM197611042951901}, Journal = {N Engl J Med}, Journal-Full = {The New England journal of medicine}, Keywords = {health, child, infant, flu, influenza, vaccination, epilepsy, seizures}, Mesh = {Age Factors; Child; Child, Preschool; Epilepsy; Female; Follow-Up Studies; Humans; Infant; Male; Recurrence; Risk; Time Factors}, Month = {Nov}, Number = {19}, Pages = {1029-33}, pmid = {972656}, Pst = {ppublish}, Title = {Predictors of epilepsy in children who have experienced febrile seizures}, Volume = {295}, Year = {1976}, url = {papers/Nelson_NEnglJMed1976.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1056/NEJM197611042951901}} @article{Klein:2010, Abstract = {OBJECTIVE: In February 2008, we alerted the Advisory Committee on Immunization Practices to preliminary evidence of a twofold increased risk of febrile seizures after the combination measles-mumps-rubella-varicella (MMRV) vaccine when compared with separate measles-mumps-rubella (MMR) and varicella vaccines. Now with data on twice as many vaccine recipients, our goal was to reexamine seizure risk after MMRV vaccine. METHODS: Using 2000-2008 Vaccine Safety Datalink data, we assessed seizures and fever visits among children aged 12 to 23 months after MMRV and separate MMR + varicella vaccines. We compared seizure risk after MMRV vaccine to that after MMR + varicella vaccines by using Poisson regression as well as with supplementary regressions that incorporated chart-review results and self-controlled analyses. RESULTS: MMRV vaccine recipients (83,107) were compared with recipients of MMR + varicella vaccines (376,354). Seizure and fever significantly clustered 7 to 10 days after vaccination with all measles-containing vaccines but not after varicella vaccination alone. Seizure risk during days 7 to 10 was higher after MMRV than after MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: 1.43-2.73]). Supplementary analyses yielded similar results. The excess risk for febrile seizures 7 to 10 days after MMRV compared with separate MMR + varicella vaccination was 4.3 per 10,000 doses (95% confidence interval: 2.6-5.6). CONCLUSIONS: Among 12- to 23-month-olds who received their first dose of measles-containing vaccine, fever and seizure were elevated 7 to 10 days after vaccination. Vaccination with MMRV results in 1 additional febrile seizure for every 2300 doses given instead of separate MMR + varicella vaccines. Providers who recommend MMRV should communicate to parents that it increases the risk of fever and seizure over that already associated with measles-containing vaccines.}, Author = {Klein, Nicola P and Fireman, Bruce and Yih, W Katherine and Lewis, Edwin and Kulldorff, Martin and Ray, Paula and Baxter, Roger and Hambidge, Simon and Nordin, James and Naleway, Allison and Belongia, Edward A and Lieu, Tracy and Baggs, James and Weintraub, Eric and {Vaccine Safety Datalink}}, Date-Added = {2013-12-12 15:49:08 +0000}, Date-Modified = {2013-12-12 16:29:51 +0000}, Doi = {10.1542/peds.2010-0665}, Journal = {Pediatrics}, Journal-Full = {Pediatrics}, Keywords = {health, child, infant, flu, influenza, vaccination, epilepsy, seizures}, Mesh = {Age Distribution; Chickenpox Vaccine; Cohort Studies; Databases, Factual; Female; Follow-Up Studies; Humans; Incidence; Infant; Male; Measles-Mumps-Rubella Vaccine; Retrospective Studies; Seizures, Febrile; Severity of Illness Index; Sex Distribution; Time Factors; Vaccination; Vaccines, Combined}, Month = {Jul}, Number = {1}, Pages = {e1-8}, pmid = {20587679}, Pst = {ppublish}, Title = {Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures}, Volume = {126}, Year = {2010}, url = {papers/Klein_Pediatrics2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1542/peds.2010-0665}} @article{Chen:2013, Abstract = {In the mammalian neocortex, segregated processing streams are thought to be important for forming sensory representations of the environment, but how local information in primary sensory cortex is transmitted to other distant cortical areas during behaviour is unclear. Here we show task-dependent activation of distinct, largely non-overlapping long-range projection neurons in the whisker region of primary somatosensory cortex (S1) in awake, behaving mice. Using two-photon calcium imaging, we monitored neuronal activity in anatomically identified S1 neurons projecting to secondary somatosensory (S2) or primary motor (M1) cortex in mice using their whiskers to perform a texture-discrimination task or a task that required them to detect the presence of an object at a certain location. Whisking-related cells were found among S2-projecting (S2P) but not M1-projecting (M1P) neurons. A higher fraction of S2P than M1P neurons showed touch-related responses during texture discrimination, whereas a higher fraction of M1P than S2P neurons showed touch-related responses during the detection task. In both tasks, S2P and M1P neurons could discriminate similarly between trials producing different behavioural decisions. However, in trials producing the same decision, S2P neurons performed better at discriminating texture, whereas M1P neurons were better at discriminating location. Sensory stimulus features alone were not sufficient to elicit these differences, suggesting that selective transmission of S1 information to S2 and M1 is driven by behaviour.}, Author = {Chen, Jerry L and Carta, Stefano and Soldado-Magraner, Joana and Schneider, Bernard L and Helmchen, Fritjof}, Date-Added = {2013-12-10 14:52:26 +0000}, Date-Modified = {2013-12-10 14:53:29 +0000}, Doi = {10.1038/nature12236}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {calcium imaging; optical physiology; neurophysiology; in vivo; mouse; Somatosensory Cortex; barrels; Motor Cortex; behavior; function; connectivity}, Mesh = {Afferent Pathways; Animals; Behavior, Animal; Calcium; Discrimination (Psychology); Mice; Neurons; Somatosensory Cortex; Vibrissae}, Month = {Jul}, Number = {7458}, Pages = {336-40}, pmid = {23792559}, Pst = {ppublish}, Title = {Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex}, Volume = {499}, Year = {2013}, url = {papers/Chen_Nature2013.pdf}} @article{Ramnani:2006, Abstract = {Evidence has been accumulating that the primate cerebellum contributes not only to motor control, but also to higher 'cognitive' function. However, there is no consensus about how the cerebellum processes such information. The answer to this puzzle can be found in the nature of cerebellar connections to areas of the cerebral cortex (particularly the prefrontal cortex) and in the uniformity of its intrinsic cellular organization, which implies uniformity in information processing regardless of the area of origin in the cerebral cortex. With this in mind, the relatively well-developed models of how the cerebellum processes information from the motor cortex might be extended to explain how it could also process information from the prefrontal cortex.}, Author = {Ramnani, Narender}, Date-Added = {2013-10-09 15:51:22 +0000}, Date-Modified = {2013-10-09 15:52:26 +0000}, Doi = {10.1038/nrn1953}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {review literature; Cerebellar Cortex; Cerebellum; function; Cerebral Cortex; Thalamic Nuclei; thalamus; Neocortex; Motor Activity/physiology; Motor Cortex; behavior;}, Mesh = {Animals; Cerebellum; Cerebral Cortex; Humans; Nerve Net; Neural Pathways}, Month = {Jul}, Number = {7}, Pages = {511-22}, pmid = {16791141}, Pst = {ppublish}, Title = {The primate cortico-cerebellar system: anatomy and function}, Volume = {7}, Year = {2006}, url = {papers/Ramnani_NatRevNeurosci2006.pdf}} @article{Altman:1969a, Author = {Altman, J}, Date-Added = {2013-10-09 15:27:38 +0000}, Date-Modified = {2013-10-09 15:27:38 +0000}, Doi = {10.1002/cne.901360303}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Age Factors; Animals; Animals, Newborn; Autoradiography; Cell Differentiation; Cell Movement; Cerebellar Cortex; Neurons; Purkinje Cells; Rats; Thymidine; Tritium}, Month = {Jul}, Number = {3}, Pages = {269-93}, pmid = {5788129}, Pst = {ppublish}, Title = {Autoradiographic and histological studies of postnatal neurogenesis. 3. Dating the time of production and onset of differentiation of cerebellar microneurons in rats}, Volume = {136}, Year = {1969}, url = {papers/Altman_JCompNeurol1969.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901360303}} @article{Ahrens:2013, Abstract = {Brain function relies on communication between large populations of neurons across multiple brain areas, a full understanding of which would require knowledge of the time-varying activity of all neurons in the central nervous system. Here we use light-sheet microscopy to record activity, reported through the genetically encoded calcium indicator GCaMP5G, from the entire volume of the brain of the larval zebrafish in vivo at 0.8 Hz, capturing more than 80% of all neurons at single-cell resolution. Demonstrating how this technique can be used to reveal functionally defined circuits across the brain, we identify two populations of neurons with correlated activity patterns. One circuit consists of hindbrain neurons functionally coupled to spinal cord neuropil. The other consists of an anatomically symmetric population in the anterior hindbrain, with activity in the left and right halves oscillating in antiphase, on a timescale of 20 s, and coupled to equally slow oscillations in the inferior olive.}, Author = {Ahrens, Misha B and Orger, Michael B and Robson, Drew N and Li, Jennifer M and Keller, Philipp J}, Date-Added = {2013-09-28 16:09:18 +0000}, Date-Modified = {2013-09-28 16:09:55 +0000}, Doi = {10.1038/nmeth.2434}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {wholeBrain; calcium imaging; calcium sensor; technique; Microscopy; Methods; Zebrafish; in vivo}, Mesh = {Animals; Brain; Microscopy; Zebrafish}, Month = {May}, Number = {5}, Pages = {413-20}, pmid = {23524393}, Pst = {ppublish}, Title = {Whole-brain functional imaging at cellular resolution using light-sheet microscopy}, Volume = {10}, Year = {2013}, url = {papers/Ahrens_NatMethods2013.pdf}, Bdsk-File-2 = {papers/Ahrens_NatMethods2013a.pdf}, Bdsk-File-3 = {papers/Ahrens_NatMethods2013.zip}} @article{Kloppel:2007, Abstract = {The neuronal correlates of handedness are still poorly understood. Here we used event-related functional magnetic resonance imaging to investigate the impact of handedness on neuronal activation of the primary sensorimotor cortex, supplementary motor area and dorsal premotor cortex during simple unilateral and bilateral finger movements. In 16 right-handed and 16 left-handed individuals, we mapped changes in regional neuronal activity while participants responded to four symbolic cues presented in a pseudorandom order. According to pre-specified cues, they pressed a button with their right, left or both index fingers or withheld a response. For unilateral right index finger button presses, reaction times, motor and premotor activity were the same for both right- and left-handers. Compared with right-handers, left-handers had shorter reaction times with unilateral left index finger button presses, along with greater activation of the supplementary motor area and right frontal opercular cortex. Simultaneous bilateral compared with unilateral button presses led to a relative increase of activity in the right and left dorsal premotor cortex and the right primary sensorimotor cortex in right but not left-handers. Neither right nor left-handers showed any tendency during bilateral button presses towards faster responses with the dominant hand and the reaction times were equal in the two groups. Therefore, we conclude that the relative increase of activity in dorsal premotor and right primary sensorimotor cortices in right-handers represents a genuine difference in bimanual motor control related to handedness.}, Author = {Kl{\"o}ppel, Stefan and van Eimeren, Thilo and Glauche, Volkmar and Vongerichten, Anna and M{\"u}nchau, Alexander and Frackowiak, Richard S J and B{\"u}chel, Christian and Weiller, Cornelius and Siebner, Hartwig R}, Date-Added = {2013-09-25 20:49:10 +0000}, Date-Modified = {2013-09-25 20:49:32 +0000}, Doi = {10.1016/j.neuroimage.2006.08.038}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb; language; fMRI}, Mesh = {Adult; Female; Functional Laterality; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Motor Cortex; Movement}, Month = {Jan}, Number = {1}, Pages = {274-80}, pmid = {17056278}, Pst = {ppublish}, Title = {The effect of handedness on cortical motor activation during simple bilateral movements}, Volume = {34}, Year = {2007}, url = {papers/Klöppel_Neuroimage2007.pdf}} @article{Li:2013a, Abstract = {Mapping cortical hemispheric asymmetries in infants would increase our understanding of the origins and developmental trajectories of hemispheric asymmetries. We analyze longitudinal cortical hemispheric asymmetries in 73 healthy subjects at birth, 1, and 2 years of age using surface-based morphometry of magnetic resonance images with a specific focus on the vertex position, sulcal depth, mean curvature, and local surface area. Prominent cortical asymmetries are found around the peri-Sylvian region and superior temporal sulcus (STS) at birth that evolve modestly from birth to 2 years of age. Sexual dimorphisms of cortical asymmetries are present at birth, with males having the larger magnitudes and sizes of the clusters of asymmetries than females that persist from birth to 2 years of age. The left supramarginal gyrus (SMG) is significantly posterior to the right SMG, and the maximum position difference increases from 10.2 mm for males (6.9 mm for females) at birth to 12.0 mm for males (8.4 mm for females) by 2 years of age. The right STS and parieto-occipital sulcus are significantly larger and deeper than those in the left hemisphere, and the left planum temporale is significantly larger and deeper than that in the right hemisphere at all 3 ages. Our results indicate that early hemispheric structural asymmetries are inherent and gender related.}, Author = {Li, Gang and Nie, Jingxin and Wang, Li and Shi, Feng and Lyall, Amanda E and Lin, Weili and Gilmore, John H and Shen, Dinggang}, Date-Added = {2013-09-25 20:46:53 +0000}, Date-Modified = {2013-09-25 20:47:26 +0000}, Doi = {10.1093/cercor/bhs413}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb; language; MRI}, Month = {Jan}, pmid = {23307634}, Pst = {aheadofprint}, Title = {Mapping Longitudinal Hemispheric Structural Asymmetries of the Human Cerebral Cortex From Birth to 2 Years of Age}, Year = {2013}, url = {papers/Li_CerebCortex2013.pdf}} @article{Hill:2010, Abstract = {We have established a population average surface-based atlas of human cerebral cortex at term gestation and used it to compare infant and adult cortical shape characteristics. Accurate cortical surface reconstructions for each hemisphere of 12 healthy term gestation infants were generated from structural magnetic resonance imaging data using a novel segmentation algorithm. Each surface was inflated, flattened, mapped to a standard spherical configuration, and registered to a target atlas sphere that reflected shape characteristics of all 24 contributing hemispheres using landmark constrained surface registration. Population average maps of sulcal depth, depth variability, three-dimensional positional variability, and hemispheric depth asymmetry were generated and compared with previously established maps of adult cortex. We found that cortical structure in term infants is similar to the adult in many respects, including the pattern of individual variability and the presence of statistically significant structural asymmetries in lateral temporal cortex, including the planum temporale and superior temporal sulcus. These results indicate that several features of cortical shape are minimally influenced by the postnatal environment.}, Author = {Hill, Jason and Dierker, Donna and Neil, Jeffrey and Inder, Terrie and Knutsen, Andrew and Harwell, John and Coalson, Timothy and Van Essen, David}, Date-Added = {2013-09-25 20:44:54 +0000}, Date-Modified = {2013-09-25 20:45:23 +0000}, Doi = {10.1523/JNEUROSCI.4682-09.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb; language; neuroimaging; fMRI}, Mesh = {Atlases as Topic; Cerebral Cortex; Female; Humans; Image Processing, Computer-Assisted; Infant, Newborn; Magnetic Resonance Imaging; Male}, Month = {Feb}, Number = {6}, Pages = {2268-76}, Pmc = {PMC2836191}, pmid = {20147553}, Pst = {ppublish}, Title = {A surface-based analysis of hemispheric asymmetries and folding of cerebral cortex in term-born human infants}, Volume = {30}, Year = {2010}, url = {papers/Hill_JNeurosci2010.pdf}} @article{Bishop:2013, Abstract = {In most people, language is processed predominantly by the left hemisphere of the brain, but we do not know how or why. A popular view is that developmental language disorders result from a poorly lateralized brain, but until recently, evidence has been weak and indirect. Modern neuroimaging methods have made it possible to study normal and abnormal development of lateralized function in the developing brain and have confirmed links with language and literacy impairments. However, there is little evidence that weak cerebral lateralization has common genetic origins with language and literacy impairments. Our understanding of the association between atypical language lateralization and developmental disorders may benefit if we reconceptualize the nature of cerebral asymmetry to recognize its multidimensionality and consider variation in lateralization over developmental time. Contrary to popular belief, cerebral lateralization may not be a highly heritable, stable characteristic of individuals; rather, weak lateralization may be a consequence of impaired language learning.}, Author = {Bishop, Dorothy V M}, Date-Added = {2013-09-25 20:40:06 +0000}, Date-Modified = {2013-09-25 20:40:11 +0000}, Doi = {10.1126/science.1230531}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; mouse; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb; language}, Mesh = {Animals; Cerebral Cortex; Cognition Disorders; Dyslexia; Forkhead Transcription Factors; Functional Laterality; Genetic Predisposition to Disease; Humans; Language Development; Language Development Disorders; Mitochondrial Proteins; Nerve Tissue Proteins; Neuronal Plasticity; Polymorphism, Single Nucleotide; Repressor Proteins; Ribosomal Proteins; Ultrasonography, Doppler, Transcranial}, Month = {Jun}, Number = {6138}, Pages = {1230531}, pmid = {23766329}, Pst = {ppublish}, Title = {Cerebral asymmetry and language development: cause, correlate, or consequence?}, Volume = {340}, Year = {2013}, url = {papers/Bishop_Science2013.pdf}} @article{Mento:2010, Abstract = {In recent years, magnetic resonance imaging has allowed researchers to individuate the earlier morphological development of the right hemisphere compared with the left hemisphere during late-gestational development. Anatomical asymmetry, however, does not necessarily mean functional asymmetry, and whether the anatomical differences between hemispheres at this early age are paralleled by functional specialisations remains unknown. In this study, the presence of lateralised electrical brain activity related to both pitch detection and discrimination was investigated in 34 prematurely-born infants [24-34 gestational weeks (GWs)] all tested at the same post-conceptional age of 35 weeks. By means of a frequency-change oddball experimental paradigm, with 'standard' tones at 1000 Hz (P = 90%) and 'deviant' tones at 2000 Hz (P = 10%), we were able to record higher right event-related potential activity in the interval windows between 350 and 650 ms after stimulus onset. An explorative hierarchical cluster analysis confirmed the different distribution of the hemispheric asymmetry score in newborns < 30 weeks old. Here, we show electrophysiological evidence of the early functional right lateralisation for pitch processing (detection and discrimination) arising by 30 GWs, but not before, in preterm newborns despite the longer environmental sensorial experience of newborns < 30 GWs. Generally, these findings suggest that the earlier right structural maturation in foetal epochs seems to be paralleled by a right functional development.}, Author = {Mento, Giovanni and Suppiej, Agnese and Alto{\`e}, Gianmarco and Bisiacchi, Patrizia S}, Date-Added = {2013-09-25 20:37:05 +0000}, Date-Modified = {2013-09-25 20:37:35 +0000}, Doi = {10.1111/j.1460-9568.2010.07076.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb; language; infant; EEG; neurophysiology}, Mesh = {Brain; Electroencephalography; Female; Functional Laterality; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Magnetic Resonance Imaging; Pitch Perception; Pregnancy}, Month = {Feb}, Number = {3}, Pages = {565-74}, pmid = {20105238}, Pst = {ppublish}, Title = {Functional hemispheric asymmetries in humans: electrophysiological evidence from preterm infants}, Volume = {31}, Year = {2010}, url = {papers/Mento_EurJNeurosci2010.pdf}} @article{Ward:1987, Abstract = {The relation between morphological variation of the corpus callosum and variation in the degree of paw preference was investigated in 129/J and BALB/cCF mice. A positive relationship explaining 24% of the variance of paw preference was found in 129/J mice; no such relationship exists in BALB/cCF mice. It is suggested that, since the genetic dissimilarity between these two inbred strains is comparable in magnitude with the genetic dissimilarity between unrelated human subjects, genetic variation may have been an uncontrolled source of heterogeneity in previous human neuropsychological studies.}, Author = {Ward, R and Tremblay, L and Lassonde, M}, Date-Added = {2013-09-25 20:04:01 +0000}, Date-Modified = {2013-09-25 20:04:08 +0000}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {Cerebral Cortex; asymmetry; lateralization; hemisphere; behavior; forelimb; handedness; Corpus Callosum}, Mesh = {Animals; Corpus Callosum; Female; Forelimb; Functional Laterality; Genetic Variation; Genotype; Male; Mice; Mice, Inbred BALB C; Mice, Inbred Strains; Sex Factors; Species Specificity}, Month = {Oct}, Number = {1}, Pages = {84-8}, pmid = {3690305}, Pst = {ppublish}, Title = {The relationship between callosal variation and lateralization in mice is genotype-dependent}, Volume = {424}, Year = {1987}, url = {papers/Ward_BrainRes1987.pdf}} @article{Fride:1990, Abstract = {Cerebral lateralization has been suggested to play a regulatory role in immune function. In this study, several measures of immune function were evaluated in mice selectively bred for either a strong (HI) or weak (LO) degree of behavioral asymmetry (paw preference) and compared to an unselected control population (HET). Both HI and LO animals had fewer spleen cells but higher degrees of [3H]thymidine incorporation into DNA (on a per cell basis) than HET mice. However, only HI mice had lower immune functions compared to HET controls manifest as reduced mixed leukocyte reaction (MLR), cytotoxic T lymphocyte (CTL) activity, and natural killer (NK) cell activity. These findings indicate that although both extremes in the degree of paw preference may be associated with deviations from the norm, a high degree of behavioral lateralization is associated with decreased immune responsiveness in this animal model.}, Author = {Fride, E and Collins, R L and Skolnick, P and Arora, P K}, Date-Added = {2013-09-25 20:01:58 +0000}, Date-Modified = {2013-09-25 20:02:30 +0000}, Journal = {Brain Behav Immun}, Journal-Full = {Brain, behavior, and immunity}, Keywords = {Cerebral Cortex; asymmetry; lateralization; hemisphere; behavior; forelimb; handedness; Corpus Callosum}, Mesh = {Animals; Behavior, Animal; Functional Laterality; Immune System; Killer Cells, Natural; Lymphocyte Culture Test, Mixed; Male; Mice; Psychoneuroimmunology; Species Specificity; T-Lymphocytes, Cytotoxic}, Month = {Jun}, Number = {2}, Pages = {129-38}, pmid = {2144194}, Pst = {ppublish}, Title = {Immune function in lines of mice selected for high or low degrees of behavioral asymmetry}, Volume = {4}, Year = {1990}} @article{Betancur:1991, Abstract = {The brain is known to modulate the immune system in an asymmetrical way. In mice, there is an association between handedness and immune response and it has also been shown that hemicortical ablation has opposite effects on some immune parameters. An association between autoantibody production and paw preference was previously observed in female mice, but not in males, suggesting that the association between immune reactivity and functional brain asymmetry is a sex-dependent phenomenon. In three independent experiments, natural killer (NK) cell activity, lymphocyte subset distribution, and mitogen-induced lymphoproliferation were assessed in male C3H/OuJIco mice selected for handedness and after unilateral cortical ablation. Handedness was shown to be associated with NK cell activity but not with lymphocyte subset distribution or lymphoproliferation. Left-handers exhibited lower NK cell activity compared to right-handed or ambidextrous animals. In contrast to previous results in female mice, mitogen-induced lymphoproliferation was not associated with handedness in males. Left cortical ablations depressed NK cell activity, while right lesions had no effect. Neither left or right lesions affected lymphocyte subsets. No interaction between paw preference and side of the lesion was found in the modulation of NK cell activity. These and previous data show that the association between paw preference and immune reactivity varies according to the sex of the animal and the immunological parameters studied. This indicates that the brain may modulate different components of the immune system in different ways, through mechanisms apparently involving sex hormones.}, Author = {Betancur, C and Neveu, P J and Vitiello, S and Le Moal, M}, Date-Added = {2013-09-25 20:01:52 +0000}, Date-Modified = {2013-09-25 20:02:30 +0000}, Journal = {Brain Behav Immun}, Journal-Full = {Brain, behavior, and immunity}, Keywords = {Cerebral Cortex; asymmetry; lateralization; hemisphere; behavior; forelimb; handedness; Corpus Callosum}, Mesh = {Animals; Brain Damage, Chronic; Cerebral Cortex; Cytotoxicity, Immunologic; Dominance, Cerebral; Functional Laterality; Humans; Killer Cells, Natural; Lymphocyte Activation; Male; Mice; Mice, Inbred C3H; Sex Characteristics; T-Lymphocyte Subsets}, Month = {Jun}, Number = {2}, Pages = {162-9}, pmid = {1893219}, Pst = {ppublish}, Title = {Natural killer cell activity is associated with brain asymmetry in male mice}, Volume = {5}, Year = {1991}, url = {papers/Betancur_BrainBehavImmun1991.pdf}} @article{Manhaes:2003, Abstract = {In the present work, the hypothesis that the ontogenetic development of the corpus callosum (CC) affects the establishment of behavioral lateralization was tested by studying paw preference performance in adult Swiss mice that were subjected to mid-sagittal transection of the CC on the first postnatal day. Magnitude and direction of laterality were evaluated independently. No significant differences between groups were found for the magnitude of paw preference. On the other hand, the transected group presented a significant populational bias favoring the left paw that was not present in the control groups. These results lend support to the hypothesis that the development of the CC plays a role in the establishment of the normal pattern of behavioral lateralization.}, Author = {Manh{\~a}es, Alex C and Krahe, Thomas E and Caparelli-D{\'a}quer, Egas and Ribeiro-Carvalho, Anderson and Schmidt, Sergio L and Filgueiras, Cl{\'a}udio C}, Date-Added = {2013-09-25 20:00:13 +0000}, Date-Modified = {2013-09-25 20:01:12 +0000}, Journal = {Neurosci Lett}, Journal-Full = {Neuroscience letters}, Keywords = {Cerebral Cortex; asymmetry; lateralization; hemisphere; behavior; forelimb; handedness; Corpus Callosum}, Mesh = {Animals; Animals, Newborn; Cell Differentiation; Corpus Callosum; Denervation; Forelimb; Functional Laterality; Growth Cones; Male; Mice; Motor Cortex; Movement}, Month = {Sep}, Number = {2}, Pages = {69-72}, pmid = {12902020}, Pst = {ppublish}, Title = {Neonatal transection of the corpus callosum affects paw preference lateralization of adult Swiss mice}, Volume = {348}, Year = {2003}, url = {papers/Manhães_NeurosciLett2003.pdf}} @article{Gruber:1991, Abstract = {Ward et al. (Brain Research 424 (1987) 84-88) have reported that reduced size of the corpus callosum (CC) was associated with a lower degree of paw preference in the mouse strain 129/J but not in the strain BALB/cCF. Both strains show individually different degrees of development of the CC but mice completely lacking CC occur rarely. The mouse strain I/LnJ shows complete agenesis of the CC. Thus, we have compared the degree of paw lateralization by means of a food reaching task in two samples of I/LnJ mice (n1 = 81, n2 = 93) with that of two common mouse strains which show a normal CC (C57BL/6JIbm, n = 44; DBA/2JZur, n = 48). The two samples of I/LnJ mice were tested in different laboratories. The first sample of I/LnJ mice had a mean age of 36 weeks. As compared to the control mice, the males but not the females showed a significantly reduced degree of paw preference. Both, callosal and acallosal mice showed a preference for left choices. The replication sample of I/LnJ mice contained only animals between 6 and 8 weeks old. All of them were ambilateral. There was no side preference and no gender difference. We conclude that congenital absence of the CC is a factor which may substantially interfere with the development of paw lateralization. However, depending on age and gender, about half of the acallosal mice develop a paw preference.}, Author = {Gruber, D and Waanders, R and Collins, R L and Wolfer, D P and Lipp, H P}, Date-Added = {2013-09-25 19:25:52 +0000}, Date-Modified = {2013-09-25 19:27:50 +0000}, Journal = {Behav Brain Res}, Journal-Full = {Behavioural brain research}, Keywords = {Cerebral Cortex; lateralization; asymmetry; hemisphere; forelimb; behavior; handedness; Corpus Callosum}, Mesh = {Agenesis of Corpus Callosum; Animals; Behavior, Animal; Brain; Corpus Callosum; Female; Foot; Functional Laterality; Male; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Neurologic Mutants}, Month = {Dec}, Number = {1}, Pages = {9-16}, pmid = {1786116}, Pst = {ppublish}, Title = {Weak or missing paw lateralization in a mouse strain (I/LnJ) with congenital absence of the corpus callosum}, Volume = {46}, Year = {1991}, url = {papers/Gruber_BehavBrainRes1991.pdf}} @article{Rogers:2009, Abstract = {Hand preferences of primates are discussed as part of the broad perspective of brain lateralization in animals, and compared with paw preferences in non-primates. Previously, it has been suggested that primates are more likely to express a species-typical hand preference on complex tasks, especially in the case of coordinated hand use in using tools. I suggest that population-level hand preferences are manifested when the task demands the obligate use of the processing specialization of one hemisphere, and that this depends on the nature of the task rather than its complexity per se. Depending on the species, simple reaching tasks may not demand the obligate use of a specialized hemisphere and so do not constrain limb/hand use. In such cases, individuals may show hand preferences that are associated with consistent differences in behaviour. The individual's hand preference is associated with the expression of behaviour controlled by the hemisphere contralateral to the preferred hand (fear and reactivity in left-handed individuals versus proactivity in right-handed individuals). Recent findings of differences in brain structure between left- and right-handed primates (e.g. somatosensory cortex in marmosets) have been discussed and related to potential evolutionary advances.}, Author = {Rogers, Lesley J}, Date-Added = {2013-09-25 13:13:42 +0000}, Date-Modified = {2013-09-25 13:15:37 +0000}, Doi = {10.1098/rstb.2008.0225}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {cerebral cortex; asymmetry; hemisphere; lateralization; handedness; forelimb; behavior}, Mesh = {Animals; Brain; Choice Behavior; Feeding Behavior; Forelimb; Functional Laterality; Hand; Humans; Individuality; Species Specificity; Tool Use Behavior; Vertebrates}, Month = {Apr}, Number = {1519}, Pages = {943-54}, Pmc = {PMC2666076}, pmid = {19064357}, Pst = {ppublish}, Title = {Hand and paw preferences in relation to the lateralized brain}, Volume = {364}, Year = {2009}, url = {papers/Rogers_PhilosTransRSocLondBBiolSci2009.pdf}} @article{Galaburda:2006a, Abstract = {All four genes thus far linked to developmental dyslexia participate in brain development, and abnormalities in brain development are increasingly reported in dyslexia. Comparable abnormalities induced in young rodent brains cause auditory and cognitive deficits, underscoring the potential relevance of these brain changes to dyslexia. Our perspective on dyslexia is that some of the brain changes cause phonological processing abnormalities as well as auditory processing abnormalities; the latter, we speculate, resolve in a proportion of individuals during development, but contribute early on to the phonological disorder in dyslexia. Thus, we propose a tentative pathway between a genetic effect, developmental brain changes, and perceptual and cognitive deficits associated with dyslexia.}, Author = {Galaburda, Albert M and LoTurco, Joseph and Ramus, Franck and Fitch, R Holly and Rosen, Glenn D}, Date-Added = {2013-09-25 12:40:21 +0000}, Date-Modified = {2013-09-25 12:41:09 +0000}, Doi = {10.1038/nn1772}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {cerebral cortex; lateralization; asymmetry; Dyslexia; neurological disorder; gene; mouse; rat; learning; behavior; hemisphere}, Mesh = {Animals; Behavior; Cognition Disorders; Disease Models, Animal; Dyslexia; Humans; Models, Molecular}, Month = {Oct}, Number = {10}, Pages = {1213-7}, pmid = {17001339}, Pst = {ppublish}, Title = {From genes to behavior in developmental dyslexia}, Volume = {9}, Year = {2006}, url = {papers/Galaburda_NatNeurosci2006.pdf}} @article{Collins:1968, Author = {Collins, R L}, Date-Added = {2013-09-25 12:30:14 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Journal = {J Hered}, Journal-Full = {The Journal of heredity}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; mouse; behavior; Forelimb; forelimb}, Mesh = {Animals; Behavior, Animal; Functional Laterality; Genetics; Hybridization, Genetic; Inbreeding; Male; Mice}, Month = {Jan-Feb}, Number = {1}, Pages = {9-12}, pmid = {5656926}, Pst = {ppublish}, Title = {On the inheritance of handedness. I. Laterality in inbred mice}, Volume = {59}, Year = {1968}, url = {papers/Collins_JHered1968.pdf}} @article{Sun:2006a, Abstract = {In the human brain, distinct functions tend to be localized in the left or right hemispheres, with language ability usually localized predominantly in the left and spatial recognition in the right. Furthermore, humans are perhaps the only mammals who have preferential handedness, with more than 90% of the population more skillful at using the right hand, which is controlled by the left hemisphere. How is a distinct function consistently localized in one side of the human brain? Because of the convergence of molecular and neurological analysis, we are beginning to consider the puzzle of brain asymmetry and handedness at a molecular level.}, Author = {Sun, Tao and Walsh, Christopher A}, Date-Added = {2013-09-25 00:16:54 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Doi = {10.1038/nrn1930}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; mouse; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb}, Mesh = {Animals; Brain; Dominance, Cerebral; Functional Laterality; Humans}, Month = {Aug}, Number = {8}, Pages = {655-62}, pmid = {16858393}, Pst = {ppublish}, Title = {Molecular approaches to brain asymmetry and handedness}, Volume = {7}, Year = {2006}, url = {papers/Sun_NatRevNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1930}} @article{Biddle:1993, Abstract = {Lateralization of paw preference in laboratory mice in a single-paw reaching task has been used as a model system for left- and right-hand usage. Given a set number of paw reaches for food from a centrally placed food tube, an individual mouse will exhibit a reliable number of left and right paw reaches. Within any single inbred strain, there are approximately equal numbers of left-pawed and right-pawed mice. Nevertheless, significant strain differences have been reported for the degree of lateralization of paw preference. We report here a systematic survey of paw preference in 12 inbred strains of the mouse in which the degree of lateralization falls into two groups of weakly lateralized and highly lateralized paw preference. The genetic inference is that a single major gene may control some function, and alternate alleles at this locus are expressed as weakly and highly lateralized paw preference. Reciprocal crosses indicate the trait is additive with no maternal or X-linked effects. The direction of paw preference has previously appeared to be genetically neutral, but in some strains there is evidence of significant deviation of the numbers of mice to the left and right of equal paw usage, independent of degree of lateralization, and this suggests that direction of left-right paw usage may be a separate genetic trait in the mouse model.}, Author = {Biddle, F G and Coffaro, C M and Ziehr, J E and Eales, B A}, Date-Added = {2013-09-25 00:15:43 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Journal = {Genome}, Journal-Full = {Genome / National Research Council Canada = G{\'e}nome / Conseil national de recherches Canada}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; mouse; behavior; forelimb}, Mesh = {Animals; Female; Functional Laterality; Genetic Variation; Male; Mice; Mice, Inbred Strains}, Month = {Oct}, Number = {5}, Pages = {935-43}, pmid = {8270204}, Pst = {ppublish}, Title = {Genetic variation in paw preference (handedness) in the mouse}, Volume = {36}, Year = {1993}, url = {papers/Biddle_Genome1993.pdf}} @article{Signore:1991, Abstract = {Mice from a pool of inbred strains (384 males and 329 females) were tested for handedness according to Collins' protocol in order to assess the reliability of this measurement. As previously reported by Collins these data revealed that a) approximately half of the mice were right-handed and half left-handed, b) most of the mice were strongly lateralized and c) females were more lateralized than males. The study of the psychometric characteristics of the test suggested that this measurement of behavioral asymmetry is both stable and observer independent. The test of paw preference also appeared to measure preexisting lateralization and was not a function of training during the test.}, Author = {Signore, P and Nosten-Bertrand, M and Chaoui, M and Roubertoux, P L and Marchaland, C and Perez-Diaz, F}, Date-Added = {2013-09-25 00:02:10 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Journal = {Physiol Behav}, Journal-Full = {Physiology \& behavior}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; mouse; behavior; forelimb}, Mesh = {Animals; Appetitive Behavior; Cerebral Cortex; Dominance, Cerebral; Female; Male; Mice; Mice, Inbred Strains; Psychomotor Performance; Sex Characteristics; Species Specificity}, Month = {Apr}, Number = {4}, Pages = {701-4}, pmid = {1881972}, Pst = {ppublish}, Title = {An assessment of handedness in mice}, Volume = {49}, Year = {1991}, url = {papers/Signore_PhysiolBehav1991.pdf}} @article{Li:2013, Author = {Li, Qingsong and Bian, Shan and Liu, Bingfang and Hong, Janet and Toth, Miklos and Sun, Tao}, Date-Added = {2013-09-24 19:34:34 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Doi = {10.1038/cr.2013.106}, Journal = {Cell Res}, Journal-Full = {Cell research}, Keywords = {Laterality; behavior; cerebral cortex; asymmetry; hemisphere; proposal; Grants; forelimb}, Month = {Sep}, Number = {9}, Pages = {1147-9}, Pmc = {PMC3760628}, pmid = {23917527}, Pst = {ppublish}, Title = {Establishing brain functional laterality in adult mice through unilateral gene manipulation in the embryonic cortex}, Volume = {23}, Year = {2013}, url = {papers/Li_CellRes2013.pdf}} @article{Mountcastle:1997, Abstract = {The modular organization of nervous systems is a widely documented principle of design for both vertebrate and invertebrate brains of which the columnar organization of the neocortex is an example. The classical cytoarchitectural areas of the neocortex are composed of smaller units, local neural circuits repeated iteratively within each area. Modules may vary in cell type and number, in internal and external connectivity, and in mode of neuronal processing between different large entities; within any single large entity they have a basic similarity of internal design and operation. Modules are most commonly grouped into entities by sets of dominating external connections. This unifying factor is most obvious for the heterotypical sensory and motor areas of the neocortex. Columnar defining factors in homotypical areas are generated, in part, within the cortex itself. The set of all modules composing such an entity may be fractionated into different modular subsets by different extrinsic connections. Linkages between them and subsets in other large entities form distributed systems. The neighborhood relations between connected subsets of modules in different entities result in nested distributed systems that serve distributed functions. A cortical area defined in classical cytoarchitectural terms may belong to more than one and sometimes to several distributed systems. Columns in cytoarchitectural areas located at some distance from one another, but with some common properties, may be linked by long-range, intracortical connections.}, Author = {Mountcastle, V B}, Date-Added = {2013-09-18 16:44:17 +0000}, Date-Modified = {2013-09-18 16:44:58 +0000}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {Neocortex; Cerebral Cortex; isocortex; cortical columns; topographic map; Anatomy; function}, Mesh = {Animals; Brain Mapping; Cell Division; Cell Movement; Cerebral Cortex; Humans; Models, Neurological; Neurons}, Month = {Apr}, Pages = {701-22}, pmid = {9153131}, Pst = {ppublish}, Title = {The columnar organization of the neocortex}, Volume = {120 ( Pt 4)}, Year = {1997}, url = {papers/Mountcastle_Brain1997.pdf}} @article{Mountcastle:1957a, Abstract = {THE METHOD of single unit analysis has now been applied to three primary sensory receiving areas of the cerebral cortex (4, 14, -15, 16, 20, 21, 22, 23, 25). Among these studies, considerable attention has been given to the somatic sensory areas, for Li et al. in an extensive series of investigations (20, 21, 22, 23) have described the responses of neurons in this region to electrical stimulation of the specific relay nucleus of the thalamus, as well as to stimulation of those thalamic nuclei they designate as unspecific, or diffusely projecting. The discharge properties of neurons of the somatic sensory areas in response to peripheral nerve volleys have been detailed by Amassian (4), and he has also given the first description of the neuronal activity of a sensory association area (5). Preliminary reports of similar studies have appeared from the Paris laboratories of Albe-Fessard (2, 3, 11). In the present investigation we wished to study the functional organiza- tion of the first somatic sensory cortex by the method of single unit analysis, and to determine as precisely as possi ble the firing patterns of cortical Cells activated by stimuli delivered to the related sense organs. We wished also to determine which modality components of somatic sensibility project upon the somatic sensory cortex, as well as to gain some idea of the functional organization of that projection. Our purposes required that the activity of cortical cells be observed over considerable periods of time in a stable fash- ion. It appears from the published records that the technique of intracellu- lar recording from cortical cells has not yet reached the stage of perfection required, for only Phillips (26, 27), dealing with the motor cortex, has been able to study cortical neurons for considerable periods of time after im- palement without deterioration of resting or action potentials. His beautiful records, however, give examples of what may be hoped for with this tech- nique. We have, therefore, persisted in the method of extracellular recording. A chamber has been developed by one of us (12) with which it is possible to obliterate cortical pulsations without the risk of direct pressure injury, yet allowing free lateral movement of the electrode carrier.}, Author = {Mountcastle, V B and Davies, P W and Berman, A L}, Date-Added = {2013-09-18 16:37:27 +0000}, Date-Modified = {2013-09-18 19:20:13 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {CEREBRAL CORTEX/physiology; cortical columns; Neocortex; Anatomy; function; topographic map; Somatosensory Cortex; cat; Classical/physiology}, Mesh = {Cerebral Cortex}, Month = {Jul}, Number = {4}, Pages = {374-407}, pmid = {13439409}, Pst = {ppublish}, Title = {Response properties of neurons of cat's somatic sensory cortex to peripheral stimuli}, Volume = {20}, Year = {1957}, url = {papers/MOUNTCASTLE_JNeurophysiol1957a.pdf}} @article{Mountcastle:1957, Abstract = {THE PRESENT PAPER describes some observations upon the modality and topographical attributes of single neurons of the first somatic sensory area of the cat's cerebral cortex, the analogue of the cortex of the postcentral gy- rus in the primate brain. These data, together with others upon the response latencies of the cells of different layers of the cortex to peripheral stimuli, support an hypothesis of the functional organization of this cortical area. This is that the neurons which lie in narrow vertical columns, or cylinders, extending from layer II through layer VI make up an elementary unit of organization, for they are activated by stimulation of the same single class of peripheral receptors, from almost identical peripheral receptive fields, at latencies which are not significantly different for the cells of the various lay- ers. It is emphasized that this pattern of organization obtains only for the early repetitiv `e responses of cortical neurons to brief peripheral stimuli. These neurons may be rela ted in quite different organization patterns when analyzed in terms of later discharges. A report of these experiments was made to the American Physiological Society in September, 1955 (10, 17).}, Author = {Mountcastle, V B}, Date-Added = {2013-09-18 16:34:47 +0000}, Date-Modified = {2013-09-18 19:20:27 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {CEREBRAL CORTEX/physiology; cortical columns; Neocortex; Anatomy; function; topographic map; Somatosensory Cortex; cat; Classical/physiology}, Mesh = {Cerebral Cortex}, Month = {Jul}, Number = {4}, Pages = {408-34}, pmid = {13439410}, Pst = {ppublish}, Title = {Modality and topographic properties of single neurons of cat's somatic sensory cortex}, Volume = {20}, Year = {1957}, url = {papers/MOUNTCASTLE_JNeurophysiol1957.pdf}} @article{Gu:2013, Abstract = {Fluorescence imaging is one of the most versatile and widely used visualization methods in biomedical research. However, tissue autofluorescence is a major obstacle confounding interpretation of in vivo fluorescence images. The unusually long emission lifetime (5-13 μs) of photoluminescent porous silicon nanoparticles can allow the time-gated imaging of tissues in vivo, completely eliminating shorter-lived (<10 ns) emission signals from organic chromophores or tissue autofluorescence. Here using a conventional animal imaging system not optimized for such long-lived excited states, we demonstrate improvement of signal to background contrast ratio by >50-fold in vitro and by >20-fold in vivo when imaging porous silicon nanoparticles. Time-gated imaging of porous silicon nanoparticles accumulated in a human ovarian cancer xenograft following intravenous injection is demonstrated in a live mouse. The potential for multiplexing of images in the time domain by using separate porous silicon nanoparticles engineered with different excited state lifetimes is discussed.}, Author = {Gu, Luo and Hall, David J and Qin, Zhengtao and Anglin, Emily and Joo, Jinmyoung and Mooney, David J and Howell, Stephen B and Sailor, Michael J}, Date-Added = {2013-09-13 17:27:37 +0000}, Date-Modified = {2013-09-13 17:28:04 +0000}, Doi = {10.1038/ncomms3326}, Journal = {Nat Commun}, Journal-Full = {Nature communications}, Keywords = {technique; Methods; in vivo; Microscopy; Dyes}, Month = {Aug}, Pages = {2326}, pmid = {23933660}, Pst = {ppublish}, Title = {In vivo time-gated fluorescence imaging with biodegradable luminescent porous silicon nanoparticles}, Volume = {4}, Year = {2013}, url = {papers/Gu_NatCommun2013.pdf}} @article{Reimann:2013, Abstract = {Brain activity generates extracellular voltage fluctuations recorded as local field potentials (LFPs). It is known that the relevant microvariables, the ionic currents across membranes, jointly generate the macrovariables, the extracellular voltage, but neither the detailed biophysical knowledge nor the required computational power have been available to model these processes. We simulated the LFP in a model of the rodent neocortical column composed of >12,000 reconstructed, multicompartmental, and spiking cortical layer 4 and 5 pyramidal neurons and basket cells, including five million dendritic and somatic compartments with voltage- and ion-dependent currents, realistic connectivity, and probabilistic AMPA, NMDA, and GABA synapses. We found that, depending on a number of factors, the LFP reflects local and cross-layer processing. Active currents dominate the generation of LFPs, not synaptic ones. Spike-related currents impact the LFP not only at higher frequencies but below 50 Hz. This work calls for re-evaluating the genesis of LFPs.}, Author = {Reimann, Michael W and Anastassiou, Costas A and Perin, Rodrigo and Hill, Sean L and Markram, Henry and Koch, Christof}, Date-Added = {2013-09-13 17:06:15 +0000}, Date-Modified = {2013-09-13 17:07:13 +0000}, Doi = {10.1016/j.neuron.2013.05.023}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Mathematics; models; Electroencephalography; LFP; EEG; neurophysiology; field potential; Neocortex; Methods}, Month = {Jul}, Number = {2}, Pages = {375-90}, Pmc = {PMC3732581}, pmid = {23889937}, Pst = {ppublish}, Title = {A biophysically detailed model of neocortical local field potentials predicts the critical role of active membrane currents}, Volume = {79}, Year = {2013}, url = {papers/Reimann_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.05.023}} @article{Zembrzycki:2013, Abstract = {The primary somatosensory cortex (S1) contains a complete body map that mirrors the subcortical maps developed by peripheral sensory input projecting to the sensory hindbrain, the thalamus and then S1. Peripheral changes during development alter these maps through 'bottom-up' plasticity. Unknown is how S1 size influences map organization and whether an altered S1 map feeds back to affect subcortical maps. We show that the size of S1 in mice is significantly reduced by cortex-specific deletion of Pax6, resulting in a reduced body map and loss of body representations by an exclusion of later-differentiating sensory thalamocortical input. An initially normal sensory thalamus was repatterned to match the aberrant S1 map by apoptotic deletion of thalamic neurons representing body parts with axons excluded from S1. Deleted representations were rescued by altering competition between thalamocortical axons using sensory deprivation or increasing the size of S1. Thus, S1 size determined the resolution and completeness of body maps and engaged 'top-down' plasticity that repatterned the sensory thalamus to match S1.}, Author = {Zembrzycki, Andreas and Chou, Shen-Ju and Ashery-Padan, Ruth and Stoykova, Anastassia and O'Leary, Dennis D M}, Date-Added = {2013-09-13 17:01:05 +0000}, Date-Modified = {2013-09-13 17:01:44 +0000}, Doi = {10.1038/nn.3454}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {mouse; topographic map; Somatosensory Cortex; connectivity; parcellation; Neocortex}, Month = {Aug}, Number = {8}, Pages = {1060-7}, Pmc = {PMC3769112}, pmid = {23831966}, Pst = {ppublish}, Title = {Sensory cortex limits cortical maps and drives top-down plasticity in thalamocortical circuits}, Volume = {16}, Year = {2013}, url = {papers/Zembrzycki_NatNeurosci2013.pdf}} @article{Ke:2013, Abstract = {We report a water-based optical clearing agent, SeeDB, which clears fixed brain samples in a few days without quenching many types of fluorescent dyes, including fluorescent proteins and lipophilic neuronal tracers. Our method maintained a constant sample volume during the clearing procedure, an important factor for keeping cellular morphology intact, and facilitated the quantitative reconstruction of neuronal circuits. Combined with two-photon microscopy and an optimized objective lens, we were able to image the mouse brain from the dorsal to the ventral side. We used SeeDB to describe the near-complete wiring diagram of sister mitral cells associated with a common glomerulus in the mouse olfactory bulb. We found the diversity of dendrite wiring patterns among sister mitral cells, and our results provide an anatomical basis for non-redundant odor coding by these neurons. Our simple and efficient method is useful for imaging intact morphological architecture at large scales in both the adult and developing brains.}, Author = {Ke, Meng-Tsen and Fujimoto, Satoshi and Imai, Takeshi}, Date-Added = {2013-09-13 17:00:01 +0000}, Date-Modified = {2013-09-13 17:00:36 +0000}, Doi = {10.1038/nn.3447}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Microscopy; technique; Methods; Imaging}, Month = {Aug}, Number = {8}, Pages = {1154-61}, pmid = {23792946}, Pst = {ppublish}, Title = {SeeDB: a simple and morphology-preserving optical clearing agent for neuronal circuit reconstruction}, Volume = {16}, Year = {2013}, url = {papers/Ke_NatNeurosci2013.pdf}} @article{Harris:2013, Abstract = {Sensory cortices receive inputs not only from thalamus but also from higher-order cortical regions. Here, Zagha et al. (2013) show that motor cortical inputs can switch barrel cortex into a desynchronized state that enables more faithful representation of subtle sensory stimuli.}, Author = {Harris, Kenneth D}, Date-Added = {2013-09-13 16:57:34 +0000}, Date-Modified = {2013-09-13 16:58:53 +0000}, Doi = {10.1016/j.neuron.2013.07.034}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {in vivo; mouse; Somatosensory Cortex; Motor Cortex; neurophysiology; Patch-Clamp Techniques; state; multimodal; spontaneous activity; review literature}, Month = {Aug}, Number = {3}, Pages = {408-10}, Pmc = {PMC3739006}, pmid = {23931991}, Pst = {ppublish}, Title = {Top-down control of cortical state}, Volume = {79}, Year = {2013}, url = {papers/Harris_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.07.034}} @article{Zagha:2013, Abstract = {Long-range corticocortical communication may have important roles in context-dependent sensory processing, yet we know very little about how these pathways influence their target regions. We studied the influence of primary motor cortex activity on primary somatosensory cortex in the mouse whisker system. We show that primary motor and somatosensory cortices undergo coherent, context-dependent changes in network state. Moreover, we show that motor cortex activity can drive changes in somatosensory cortex network state. A series of experiments demonstrate the involvement of the direct corticocortical feedback pathway, providing temporally precise and spatially targeted modulation of network dynamics. Cortically mediated changes in network state significantly impact sensory coding, with activated states increasing the reliability of responses to complex stimuli. By influencing network state, corticocortical communication from motor cortex may ensure that during active exploration the relevant sensory region is primed for enhanced sensory discrimination.}, Author = {Zagha, Edward and Casale, Amanda E and Sachdev, Robert N S and McGinley, Matthew J and McCormick, David A}, Date-Added = {2013-09-13 16:57:29 +0000}, Date-Modified = {2013-09-13 16:58:40 +0000}, Doi = {10.1016/j.neuron.2013.06.008}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {in vivo; mouse; Somatosensory Cortex; Motor Cortex; neurophysiology; Patch-Clamp Techniques; state; multimodal; spontaneous activity;}, Month = {Aug}, Number = {3}, Pages = {567-78}, Pmc = {PMC3742632}, pmid = {23850595}, Pst = {ppublish}, Title = {Motor cortex feedback influences sensory processing by modulating network state}, Volume = {79}, Year = {2013}, url = {papers/Zagha_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.06.008}} @article{Olcese:2013, Abstract = {Multisensory integration (MI) is crucial for sensory processing, but it is unclear how MI is organized in cortical microcircuits. Whole-cell recordings in a mouse visuotactile area located between primary visual and somatosensory cortices revealed that spike responses were less bimodal than synaptic responses but displayed larger multisensory enhancement. MI was layer and cell type specific, with multisensory enhancement being rare in the major class of inhibitory interneurons and in the output infragranular layers. Optogenetic manipulation of parvalbumin-positive interneuron activity revealed that the scarce MI of interneurons enables MI in neighboring pyramids. Finally, single-cell resolution calcium imaging revealed a gradual merging of modalities: unisensory neurons had higher densities toward the borders of the primary cortices, but were located in unimodal clusters in the middle of the cortical area. These findings reveal the role of different neuronal subcircuits in the synaptic process of MI in the rodent parietal cortex.}, Author = {Olcese, Umberto and Iurilli, Giuliano and Medini, Paolo}, Date-Added = {2013-09-13 16:55:06 +0000}, Date-Modified = {2013-09-13 16:56:09 +0000}, Doi = {10.1016/j.neuron.2013.06.010}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {in vivo; mouse; Patch-Clamp Techniques; calcium imaging; Somatosensory Cortex; motor; multimodal; topographic map}, Month = {Aug}, Number = {3}, Pages = {579-93}, pmid = {23850594}, Pst = {ppublish}, Title = {Cellular and synaptic architecture of multisensory integration in the mouse neocortex}, Volume = {79}, Year = {2013}, url = {papers/Olcese_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.06.010}} @article{Partanen:2013, Abstract = {Learning, the foundation of adaptive and intelligent behavior, is based on plastic changes in neural assemblies, reflected by the modulation of electric brain responses. In infancy, auditory learning implicates the formation and strengthening of neural long-term memory traces, improving discrimination skills, in particular those forming the prerequisites for speech perception and understanding. Although previous behavioral observations show that newborns react differentially to unfamiliar sounds vs. familiar sound material that they were exposed to as fetuses, the neural basis of fetal learning has not thus far been investigated. Here we demonstrate direct neural correlates of human fetal learning of speech-like auditory stimuli. We presented variants of words to fetuses; unlike infants with no exposure to these stimuli, the exposed fetuses showed enhanced brain activity (mismatch responses) in response to pitch changes for the trained variants after birth. Furthermore, a significant correlation existed between the amount of prenatal exposure and brain activity, with greater activity being associated with a higher amount of prenatal speech exposure. Moreover, the learning effect was generalized to other types of similar speech sounds not included in the training material. Consequently, our results indicate neural commitment specifically tuned to the speech features heard before birth and their memory representations.}, Author = {Partanen, Eino and Kujala, Teija and N{\"a}{\"a}t{\"a}nen, Risto and Liitola, Auli and Sambeth, Anke and Huotilainen, Minna}, Date-Added = {2013-09-13 16:32:38 +0000}, Date-Modified = {2013-09-13 16:32:38 +0000}, Doi = {10.1073/pnas.1302159110}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {event-related potentials; mismatch negativity}, Month = {Sep}, Number = {37}, Pages = {15145-50}, pmid = {23980148}, Pst = {ppublish}, Title = {Learning-induced neural plasticity of speech processing before birth}, Volume = {110}, Year = {2013}, url = {papers/Partanen_ProcNatlAcadSciUSA2013.pdf}} @article{Borjigin:2013, Abstract = {The brain is assumed to be hypoactive during cardiac arrest. However, the neurophysiological state of the brain immediately following cardiac arrest has not been systematically investigated. In this study, we performed continuous electroencephalography in rats undergoing experimental cardiac arrest and analyzed changes in power density, coherence, directed connectivity, and cross-frequency coupling. We identified a transient surge of synchronous gamma oscillations that occurred within the first 30 s after cardiac arrest and preceded isoelectric electroencephalogram. Gamma oscillations during cardiac arrest were global and highly coherent; moreover, this frequency band exhibited a striking increase in anterior-posterior-directed connectivity and tight phase-coupling to both theta and alpha waves. High-frequency neurophysiological activity in the near-death state exceeded levels found during the conscious waking state. These data demonstrate that the mammalian brain can, albeit paradoxically, generate neural correlates of heightened conscious processing at near-death.}, Author = {Borjigin, Jimo and Lee, Uncheol and Liu, Tiecheng and Pal, Dinesh and Huff, Sean and Klarr, Daniel and Sloboda, Jennifer and Hernandez, Jason and Wang, Michael M and Mashour, George A}, Date-Added = {2013-09-13 16:25:07 +0000}, Date-Modified = {2013-09-13 16:25:07 +0000}, Doi = {10.1073/pnas.1308285110}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {consciousness; global hypoxia; global ischemia; near-death experience}, Month = {Aug}, Number = {35}, Pages = {14432-7}, Pmc = {PMC3761619}, pmid = {23940340}, Pst = {ppublish}, Title = {Surge of neurophysiological coherence and connectivity in the dying brain}, Volume = {110}, Year = {2013}, url = {papers/Borjigin_ProcNatlAcadSciUSA2013.pdf}} @article{Berger:2007, Abstract = {Cortical dynamics can be imaged at high spatiotemporal resolution with voltage-sensitive dyes (VSDs) and calcium-sensitive dyes (CaSDs). We combined these two imaging techniques using epifluorescence optics together with whole cell recordings to measure the spatiotemporal dynamics of activity in the mouse somatosensory barrel cortex in vitro and in the supragranular layers in vivo. The two optical signals reported distinct aspects of cortical function. VSD fluorescence varied linearly with membrane potential and was dominated by subthreshold postsynaptic potentials, whereas the CaSD signal predominantly reflected local action potential firing. Combining VSDs and CaSDs allowed us to monitor the synaptic drive and the spiking activity of a given area at the same time in the same preparation. The spatial extent of the two dye signals was different, with VSD signals spreading further than CaSD signals, reflecting broad subthreshold and narrow suprathreshold receptive fields. Importantly, the signals from the dyes were differentially affected by pharmacological manipulations, stimulation strength, and depth of isoflurane anesthesia. Combined VSD and CaSD measurements can therefore be used to specify the temporal and spatial relationships between subthreshold and suprathreshold activity of the neocortex.}, Author = {Berger, Thomas and Borgdorff, Aren and Crochet, Sylvain and Neubauer, Florian B and Lefort, Sandrine and Fauvet, Bruno and Ferezou, Isabelle and Carleton, Alan and L{\"u}scher, Hans-Rudolf and Petersen, Carl C H}, Date-Added = {2013-09-10 16:45:21 +0000}, Date-Modified = {2013-09-10 16:46:01 +0000}, Doi = {10.1152/jn.01178.2006}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {calcium imaging; Multiphoton; Microscopy; technical report; voltage sensor; neurophysiology}, Mesh = {Analysis of Variance; Animals; Brain Mapping; Fluorescent Dyes; Image Processing, Computer-Assisted; Larva; Membrane Potentials; Mice; Mice, Inbred C57BL; Microscopy, Fluorescence; Nerve Net; Nonlinear Dynamics; Patch-Clamp Techniques; Photic Stimulation; Somatosensory Cortex; Vibrissae; Xenopus}, Month = {May}, Number = {5}, Pages = {3751-62}, pmid = {17360827}, Pst = {ppublish}, Title = {Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex}, Volume = {97}, Year = {2007}, url = {papers/Berger_JNeurophysiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01178.2006}} @article{Vogelstein:2010, Abstract = {Fluorescent calcium indicators are becoming increasingly popular as a means for observing the spiking activity of large neuronal populations. Unfortunately, extracting the spike train of each neuron from a raw fluorescence movie is a nontrivial problem. This work presents a fast nonnegative deconvolution filter to infer the approximately most likely spike train of each neuron, given the fluorescence observations. This algorithm outperforms optimal linear deconvolution (Wiener filtering) on both simulated and biological data. The performance gains come from restricting the inferred spike trains to be positive (using an interior-point method), unlike the Wiener filter. The algorithm runs in linear time, and is fast enough that even when simultaneously imaging >100 neurons, inference can be performed on the set of all observed traces faster than real time. Performing optimal spatial filtering on the images further refines the inferred spike train estimates. Importantly, all the parameters required to perform the inference can be estimated using only the fluorescence data, obviating the need to perform joint electrophysiological and imaging calibration experiments.}, Author = {Vogelstein, Joshua T and Packer, Adam M and Machado, Timothy A and Sippy, Tanya and Babadi, Baktash and Yuste, Rafael and Paninski, Liam}, Date-Added = {2013-09-10 14:51:05 +0000}, Date-Modified = {2013-09-10 14:51:55 +0000}, Doi = {10.1152/jn.01073.2009}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {methods; technical report; calcium imaging; Multiphoton; Computers}, Mesh = {Action Potentials; Algorithms; Calcium Signaling; Computer Simulation; Fluorescent Dyes; Microscopy, Fluorescence; Microscopy, Video; Models, Neurological; Neurons; Normal Distribution; Poisson Distribution; Signal Processing, Computer-Assisted; Time Factors}, Month = {Dec}, Number = {6}, Pages = {3691-704}, Pmc = {PMC3007657}, pmid = {20554834}, Pst = {ppublish}, Title = {Fast nonnegative deconvolution for spike train inference from population calcium imaging}, Volume = {104}, Year = {2010}, url = {papers/Vogelstein_JNeurophysiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01073.2009}} @article{Ko:2013, Abstract = {Sensory processing occurs in neocortical microcircuits in which synaptic connectivity is highly structured and excitatory neurons form subnetworks that process related sensory information. However, the developmental mechanisms underlying the formation of functionally organized connectivity in cortical microcircuits remain unknown. Here we directly relate patterns of excitatory synaptic connectivity to visual response properties of neighbouring layer 2/3 pyramidal neurons in mouse visual cortex at different postnatal ages, using two-photon calcium imaging in vivo and multiple whole-cell recordings in vitro. Although neural responses were already highly selective for visual stimuli at eye opening, neurons responding to similar visual features were not yet preferentially connected, indicating that the emergence of feature selectivity does not depend on the precise arrangement of local synaptic connections. After eye opening, local connectivity reorganized extensively: more connections formed selectively between neurons with similar visual responses and connections were eliminated between visually unresponsive neurons, but the overall connectivity rate did not change. We propose a sequential model of cortical microcircuit development based on activity-dependent mechanisms of plasticity whereby neurons first acquire feature preference by selecting feedforward inputs before the onset of sensory experience--a process that may be facilitated by early electrical coupling between neuronal subsets--and then patterned input drives the formation of functional subnetworks through a redistribution of recurrent synaptic connections.}, Author = {Ko, Ho and Cossell, Lee and Baragli, Chiara and Antolik, Jan and Clopath, Claudia and Hofer, Sonja B and Mrsic-Flogel, Thomas D}, Date-Added = {2013-09-10 14:10:22 +0000}, Date-Modified = {2013-09-10 14:12:25 +0000}, Doi = {10.1038/nature12015}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {activity-development; topographic map; visual system; Visual Cortex; Multiphoton; calcium imaging; Patch-Clamp Techniques; in vivo; mouse; currOpinRvw}, Mesh = {Animals; Animals, Newborn; Eye; Eyelids; Mice; Mice, Inbred C57BL; Models, Neurological; Movement; Neural Pathways; Neuronal Plasticity; Pyramidal Cells; Synapses; Visual Cortex; Visual Perception}, Month = {Apr}, Number = {7443}, Pages = {96-100}, pmid = {23552948}, Pst = {ppublish}, Title = {The emergence of functional microcircuits in visual cortex}, Volume = {496}, Year = {2013}, url = {papers/Ko_Nature2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature12015}} @article{Van-Hooser:2012, Abstract = {Visual experience plays a critical role in the development of direction-selective responses in ferret visual cortex. In visually naive animals, presentation of a bidirectional "training" stimulus induces rapid increases in the direction-selective responses of single neurons that can be predicted by small but significant direction biases that are present in neighboring neurons at the onset of stimulation. In this study we used in vivo two-photon imaging of calcium signals to further explore the contribution of visual experience to the emergence of direction- selective responses in ferret visual cortex. The first set of experiments was designed to determine whether visual experience is required for the development of the initial neighborhood bias. In animals that were dark-reared until the time of eye opening, we found that individual neurons exhibited weak direction-selective responses accompanied by a reduced but statistically significant neighborhood bias, indicating that both features arise without the need for visual experience. The second set of experiments used a unidirectional training stimulus to assess the relative roles of the neighborhood bias and visual experience in determining the direction preference that cortical neurons acquire during direction training. We found that neurons became more responsive to the trained direction even when they were located in regions of the cortex with an initial neighborhood bias for the direction opposite the training stimulus. Together, these results suggest an adaptive developmental strategy for the elaboration of direction-selective responses, one in which experience-independent mechanisms provide a symmetry-breaking seed for the instructive effects of visual experience.}, Author = {Van Hooser, Stephen D and Li, Ye and Christensson, Maria and Smith, Gordon B and White, Leonard E and Fitzpatrick, David}, Date-Added = {2013-08-28 14:55:59 +0000}, Date-Modified = {2013-08-28 14:57:57 +0000}, Doi = {10.1523/JNEUROSCI.0230-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {topographic map; visual system; ferret; Visual Cortex; calcium imaging; optical physiology; currOpinRvw; activity-development;}, Mesh = {Animals; Female; Ferrets; Male; Molecular Imaging; Motion Perception; Neurons; Photic Stimulation; Visual Cortex; Visual Perception}, Month = {May}, Number = {21}, Pages = {7258-66}, Pmc = {PMC3368384}, pmid = {22623671}, Pst = {ppublish}, Title = {Initial neighborhood biases and the quality of motion stimulation jointly influence the rapid emergence of direction preference in visual cortex}, Volume = {32}, Year = {2012}, url = {papers/VanHooser_JNeurosci2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0230-12.2012}} @article{Soto:2012, Abstract = {Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell-type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx), photoreceptors fail to establish normal connections with bipolar cells (BCs). Here, we find that retinal ganglion cells (RGCs) in Crx⁻/⁻ mice become rhythmically hyperactive around the time of eye opening as a result of increased spontaneous glutamate release from BCs. This elevated neurotransmission enhances synaptogenesis between BCs and RGCs, without altering the overall circuit architecture. Using live imaging, we discover that spontaneous activity selectively regulates the rate of synapse formation, not elimination, in this circuit. Reconstructions of the connectivity patterns of three BC types with a shared RGC target further revealed that neurotransmission specifically promotes the formation of multisynaptic appositions from one BC type without affecting the maintenance or elimination of connections from the other two. Although hyperactivity in Crx⁻/⁻ mice persists, synapse numbers do not increase beyond 4 weeks of age, suggesting closure of a critical period for synaptic refinement in the inner retina. Interestingly, despite their hyperactivity, RGC axons maintain normal eye-specific territories and cell-type-specific layers in the dorsal lateral geniculate nucleus.}, Author = {Soto, Florentina and Ma, Xiaofeng and Cecil, Jacob L and Vo, Bradly Q and Culican, Susan M and Kerschensteiner, Daniel}, Date-Added = {2013-08-28 14:29:07 +0000}, Date-Modified = {2013-08-28 14:29:52 +0000}, Doi = {10.1523/JNEUROSCI.0194-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {spontaneous activity; activity-dependent; Retina; Glutamate; bipolar cells; Retinal Ganglion Cells; retinal waves; currOpinRvw}, Mesh = {Action Potentials; Age Factors; Animals; Animals, Newborn; Biophysics; Calcium Channels; Calcium-Binding Protein, Vitamin D-Dependent; Cholera Toxin; Choline O-Acetyltransferase; Electric Stimulation; Excitatory Postsynaptic Potentials; Eye; Female; Gene Expression Regulation, Developmental; Geniculate Bodies; Guanylate Kinase; Homeodomain Proteins; Injections, Intraocular; Luminescent Proteins; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurogenesis; Neurons; Neurotransmitter Agents; Patch-Clamp Techniques; Peanut Agglutinin; Periodicity; Presynaptic Terminals; Receptors, Dopamine D4; Retina; Retinal Ganglion Cells; Rhodopsin; Synapses; Trans-Activators; Transfection; Vesicular Glutamate Transport Protein 1; Visual Pathways}, Month = {Apr}, Number = {16}, Pages = {5426-39}, Pmc = {PMC3353326}, pmid = {22514306}, Pst = {ppublish}, Title = {Spontaneous activity promotes synapse formation in a cell-type-dependent manner in the developing retina}, Volume = {32}, Year = {2012}, url = {papers/Soto_JNeurosci2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0194-12.2012}} @article{Kuhl:2010, Abstract = {The last decade has produced an explosion in neuroscience research examining young children's early processing of language. Noninvasive, safe functional brain measurements have now been proven feasible for use with children starting at birth. The phonetic level of language is especially accessible to experimental studies that document the innate state and the effect of learning on the brain. The neural signatures of learning at the phonetic level can be documented at a remarkably early point in development. Continuity in linguistic development from infants' earliest brain responses to phonetic stimuli is reflected in their language and prereading abilities in the second, third, and fifth year of life, a finding with theoretical and clinical impact. There is evidence that early mastery of the phonetic units of language requires learning in a social context. Neuroscience on early language learning is beginning to reveal the multiple brain systems that underlie the human language faculty.}, Author = {Kuhl, Patricia K}, Date-Added = {2013-08-28 14:07:15 +0000}, Date-Modified = {2013-08-28 14:07:53 +0000}, Doi = {10.1016/j.neuron.2010.08.038}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {development; Cerebral Cortex; Language Development Disorders; Dyslexia; function; human; review literature; currOpinRvw}, Mesh = {Brain; Cognition; Computer Simulation; Critical Period (Psychology); Evoked Potentials; Humans; Interpersonal Relations; Language; Language Development; Verbal Learning}, Month = {Sep}, Number = {5}, Pages = {713-27}, Pmc = {PMC2947444}, pmid = {20826304}, Pst = {ppublish}, Title = {Brain mechanisms in early language acquisition}, Volume = {67}, Year = {2010}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.08.038}} @article{Antonini:1993a, Abstract = {If vision in one eye is blurred or occluded during a critical period in postnatal development, neurons in the visual cortex lose their responses to stimulation through that eye within a few days. Anatomical changes in the nerve terminals that provide input to the visual cortex have previously been observed only after weeks of deprivation, suggesting that synapses become physiologically ineffective before the branches on which they sit are withdrawn. Reconstruction of single geniculocortical axonal arbors in the cat after either brief or prolonged monocular occlusion revealed striking axonal rearrangements in both instances. Rapid withdrawal of the branches of deprived-eye arbors suggests that axonal branches bearing synapses respond quickly to changing patterns of neuronal activity.}, Author = {Antonini, A and Stryker, M P}, Date-Added = {2013-08-27 20:36:05 +0000}, Date-Modified = {2013-08-27 20:36:05 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Animals; Axons; Cats; Geniculate Bodies; Neuronal Plasticity; Neurons, Afferent; Photic Stimulation; Vision, Ocular; Visual Cortex}, Month = {Jun}, Number = {5115}, Pages = {1819-21}, pmid = {8511592}, Pst = {ppublish}, Title = {Rapid remodeling of axonal arbors in the visual cortex}, Volume = {260}, Year = {1993}} @article{Antonini:1993, Abstract = {This study analyzes the morphological changes in geniculocortical axons terminating in the primary visual cortex of the cat, during the period in which, in normal development, the terminals in layer IV undergo an eye-specific segregation. Geniculocortical afferent fibers were filled anterogradely by the Phaseolus lectin (PHA-L) injected into the main laminae of the LGN. After standard immunohistochemical procedures, single axons were serially reconstructed in two or three dimensions. Experiments were performed in normal kittens and in kittens in which retinal activity was continuously blocked by repeated intraocular injections of TTX. In normal kittens, arbors were reconstructed at four different ages (19, 23, 30-31, and 39 days postnatally) spanning the period during which the geniculocortical projection segregates into eye-specific columns in layer IV (LeVay et al., 1978). Results reveal that sparse but widely extending branches characteristic of young arbors are eliminated during normal development at the same time as selected portions of the arbor grow considerably in length and complexity. The terminal arborizations also subdivide into distinct patches of terminals, consistent with the segregation of left and right eye afferents. In TTX-treated animals, axonal arbors reconstructed at postnatal days 23, 29, and 39 show a complexity and extent of terminal arborization similar to that of normal animals, though more variable in size and degree of elaboration. No progressive changes are evident with age. Further, the majority of arbors reconstructed from TTX-treated animals lack the patchy organization typical of normal animals.}, Author = {Antonini, A and Stryker, M P}, Date-Added = {2013-08-27 20:36:00 +0000}, Date-Modified = {2013-08-27 20:37:51 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {visual system; cat; retina; Thalamic Nuclei; LGN; activity manipulation; spontaneous activity; retinal waves; Anatomy; currOpinRvw}, Mesh = {Afferent Pathways; Animals; Axons; Cats; Geniculate Bodies; Immunoenzyme Techniques; Immunohistochemistry; Phytohemagglutinins; Retina; Tetrodotoxin; Visual Cortex}, Month = {Aug}, Number = {8}, Pages = {3549-73}, pmid = {8340819}, Pst = {ppublish}, Title = {Development of individual geniculocortical arbors in cat striate cortex and effects of binocular impulse blockade}, Volume = {13}, Year = {1993}} @article{Furman:2013, Abstract = {Prior to eye opening, waves of spontaneous activity sweep across the developing retina. These "retinal waves", together with genetically encoded molecular mechanisms, mediate the formation of visual maps in the brain. However, the specific role of wave activity in synapse development in retino-recipient brain regions is unclear. Here, we compare the functional development of synapses and the morphological development of neurons in the superior colliculus (SC) of wild-type mice (WT) and transgenic mice (β2-TG) in which retinal wave propagation is spatially truncated (Xu et al., 2011). We use two recently developed brain slice preparations to examine neurons and synapses in the binocular vs. mainly-monocular SC. We find that retinocollicular synaptic strength is reduced whereas the number of retinal inputs is increased in the binocular SC of β2-TG mice in comparison to WT mice. In contrast, in the mainly-monocular SC, the number of retinal inputs is normal in β2-TG mice, but transiently, synapses are abnormally strong, possibly due to enhanced activity-dependent competition between local, 'small' retinal domains. These findings demonstrate that retinal wave size plays an instructive role in the synaptic and morphological development of SC neurons, possibly through a competitive process among retinofugal axons.}, Author = {Furman, Moran and Xu, Hong-Ping and Crair, Michael C}, Date-Added = {2013-08-27 20:19:20 +0000}, Date-Modified = {2013-08-27 20:21:27 +0000}, Doi = {10.1152/jn.01066.2012}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {retinal waves; spontaneous activity; synapses; Patch-Clamp Techniques; in vitro; mice; mouse; Neurophysiology; activity-dependent; development; retinal waves; superior colliculus; vision; currOpinRvw}, Month = {Jun}, pmid = {23741047}, Pst = {aheadofprint}, Title = {Competition driven by retinal waves promotes the morphological and functional synaptic development of neurons in the superior colliculus}, Year = {2013}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01066.2012}} @article{Furman:2012, Abstract = {In the developing visual system of mammals, retinal axons from the two eyes compete for postsynaptic partners. After eye opening, this process is regulated in part by homeostatically constrained competition for synaptic connectivity with target neurons. However, prior to eye opening, the functional and synaptic basis of binocular map development is unclear. To examine the role of binocular interactions during early stages of visual map development, we performed in vitro patch-clamp recordings from the superior colliculus (SC) of neonatal mice. Using newly designed slice preparations, we compared retinocollicular synapse development in the medial SC, which receives binocular input, and the lateral SC, which is predominantly monocular. Surprisingly, we found that at P6-7, when eye-specific segregation has just emerged, retinocollicular synapses were stronger and more mature and dendritic arbors were more elaborate in the medial than the lateral SC. Furthermore, monocular enucleation of the ipsilateral eye at P0 selectively reduced synaptic strength and dendritic branching in the medial SC and abolished the differences normally observed between the two slices at P6-7. This specifically implicates binocular interactions in the development of retinocollicular connectivity prior to eye opening. Our findings contrast with the predictions of a constrained-connectivity model of binocular map development and suggest instead that binocular competition prior to eye opening enhances retinocollicular synaptic strength and the morphological development of retino-recipient neurons.}, Author = {Furman, Moran and Crair, Michael C}, Date-Added = {2013-08-27 20:19:16 +0000}, Date-Modified = {2013-08-27 20:21:35 +0000}, Doi = {10.1152/jn.00943.2011}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {retinal waves; spontaneous activity; synapses; Patch-Clamp Techniques; in vitro; mice; mouse; Neurophysiology; activity-dependent; development; retinal waves; superior colliculus; vision; currOpinRvw}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Eye; Female; Male; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Organ Culture Techniques; Retina; Superior Colliculi; Synapses; Vision, Binocular; Visual Pathways}, Month = {Jun}, Number = {11}, Pages = {3200-16}, pmid = {22402661}, Pst = {ppublish}, Title = {Synapse maturation is enhanced in the binocular region of the retinocollicular map prior to eye opening}, Volume = {107}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00943.2011}} @article{Turrigiano:2011, Abstract = {Maintaining the proper balance between excitation and inhibition is critical for the normal function of cortical circuits. This balance is thought to be maintained by an array of homeostatic mechanisms that regulate neuronal and circuit excitability, including mechanisms that target excitatory and inhibitory synapses, and mechanisms that target intrinsic neuronal excitability. In this review, I discuss where and when these mechanisms are used in complex microcircuits, what is currently known about the signaling pathways that underlie them, and how these different ways of achieving network stability cooperate and/or compete. An important challenge for the field of homeostatic plasticity is to assemble our understanding of these individual mechanisms into a coherent view of how microcircuit stability is maintained during experience-dependent circuit refinement.}, Author = {Turrigiano, Gina}, Date-Added = {2013-08-27 20:12:28 +0000}, Date-Modified = {2013-08-27 20:15:22 +0000}, Doi = {10.1146/annurev-neuro-060909-153238}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {Visual Cortex; plasticity; homeostatic plasticity; neurophysiology; currOpinRvw}, Mesh = {Animals; Cerebral Cortex; Homeostasis; Models, Neurological; Nerve Net; Neurons; Synapses}, Pages = {89-103}, pmid = {21438687}, Pst = {ppublish}, Title = {Too many cooks? Intrinsic and synaptic homeostatic mechanisms in cortical circuit refinement}, Volume = {34}, Year = {2011}, url = {papers/Turrigiano_AnnuRevNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev-neuro-060909-153238}} @article{Levelt:2012, Abstract = {In many regions of the developing brain, neuronal circuits undergo defined phases of enhanced plasticity, termed critical periods. Work in the rodent visual cortex has led to important insights into the cellular and molecular mechanisms regulating the timing of the critical period. Although there is little doubt that the maturation of specific inhibitory circuits plays a key role in the opening of the critical period in the visual cortex, it is less clear what puts an end to it. In this review, we describe the established mechanisms and point out where more experimental work is needed. We also show that plasticity in the visual cortex is present well before, and long after, the peak of the critical period.}, Author = {Levelt, Christiaan N and H{\"u}bener, Mark}, Date-Added = {2013-08-27 20:08:58 +0000}, Date-Modified = {2013-08-27 20:09:57 +0000}, Doi = {10.1146/annurev-neuro-061010-113813}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {activity-development; visual system; Visual Cortex; plasticity; Critical Period; currOpinRvw}, Mesh = {Aging; Animals; Critical Period (Psychology); Dominance, Ocular; Humans; Models, Neurological; Neural Inhibition; Neuronal Plasticity; Signal Transduction; Synaptic Transmission; Visual Cortex}, Pages = {309-30}, pmid = {22462544}, Pst = {ppublish}, Title = {Critical-period plasticity in the visual cortex}, Volume = {35}, Year = {2012}, url = {papers/Levelt_AnnuRevNeurosci2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev-neuro-061010-113813}} @article{Syed:2004a, Abstract = {Spontaneous rhythmic waves in the developing mammalian retina are thought to propagate among differentiated neurons in the inner retina (IR) and play an important role in activity-dependent visual development. Here we report a new form of rhythmic Ca(2+) wave in the ventricular zone (VZ) of the developing rabbit retina. Ca(2+) imaging from two-photon optical sections near the ventricular surface of the whole-mount retina showed rhythmic Ca(2+) transients propagating laterally as waves. The VZ waves had a distinctively slow Ca(2+) dynamics (lasting approximately 20 s) but shared a similar frequency and propagation speed with the IR waves. Simultaneous Ca(2+) imaging in VZ and multi-electrode array recording in the ganglion cell layer (GCL) revealed close spatiotemporal correlation between spontaneous VZ and IR waves, suggesting a common source of initiation and/or regulation of the two waves. Pharmacological studies further showed that all drugs that blocked IR waves also blocked VZ waves. However, the muscarinic antagonist atropine selectively blocked VZ but not IR waves at this developmental stage, indicating that IR waves were not dependent on VZ waves, but VZ waves likely relied on the initiation of IR waves. Eliciting IR waves with puffs of nicotinic or non-N-methyl-d-aspartate agonists in GCL produced atropine-sensitive waves in the VZ, demonstrating a unique, retrograde signaling pathway from IR to VZ. Thus differentiated neurons in the IR use spontaneous, rhythmic waves to send both forward signals to the central visual targets and retrograde messages to the developing cells in the VZ.}, Author = {Syed, Mohsin Md and Lee, Seunghoon and He, Shigang and Zhou, Z Jimmy}, Date-Added = {2013-08-14 20:09:04 +0000}, Date-Modified = {2013-08-14 20:09:44 +0000}, Doi = {10.1152/jn.01129.2003}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {retinal waves, spontaneous activity; activity-development; calcium imaging; retina; visual system}, Mesh = {Animals; Atropine; Axons; Calcium; Calcium Signaling; Cell Differentiation; Cholinergic Antagonists; Electrodes; Excitatory Amino Acid Agonists; Female; GABA Antagonists; Image Processing, Computer-Assisted; Microscopy, Fluorescence; Muscarinic Antagonists; Neurotransmitter Agents; Pregnancy; Rabbits; Retina; Retinal Ganglion Cells; Synaptic Transmission}, Month = {May}, Number = {5}, Pages = {1999-2009}, pmid = {14681336}, Pst = {ppublish}, Title = {Spontaneous waves in the ventricular zone of developing mammalian retina}, Volume = {91}, Year = {2004}, url = {papers/Syed_JNeurophysiol2004.pdf}} @article{Copenhagen:1996, Abstract = {Propagated waves of excitation in developing neural tissues may be a critical feature of maturation. Recent findings shed new light on the mechanisms underlying these waves.}, Author = {Copenhagen, D R}, Date-Added = {2013-08-14 16:25:40 +0000}, Date-Modified = {2013-08-14 16:26:17 +0000}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {retinal waves; Spontaneous activity; review}, Mesh = {Animals; Retina; Signal Transduction}, Month = {Nov}, Number = {11}, Pages = {1368-70}, pmid = {8939594}, Pst = {ppublish}, Title = {Retinal development: on the crest of an exciting wave}, Volume = {6}, Year = {1996}, url = {papers/Copenhagen_CurrBiol1996.pdf}} @article{Zhou:1998, Abstract = {Spontaneous, rhythmic waves of excitation in the developing mammalian retina play a critical role in the formation of precise neuronal connectivity in the visual system. However, it is not known what circuits in the retina are responsible for the production of these waves. Using patch-clamp recordings in the whole-mount neonatal rabbit retina, this study reports that the displaced starburst amacrine cell, a unique cholinergic interneuron in the ganglion cell layer of the retina, undergoes rhythmic bursts of membrane depolarization with a frequency and duration similar to those of spontaneous retinal waves. Simultaneous patch-clamp recordings from pairs of neighboring starburst and ganglion cells show that the rhythmic activity in starburst cells is closely correlated with that in ganglion cells, and that the excitation in both cell types is most likely driven by synaptic input. However, in contrast to ganglion cells, displaced starburst cells usually do not generate spontaneous somatic action potentials. Instead, they seem to use subthreshold potentials (at least at the soma) to mediate the rhythmic excitation. The results suggest that acetylcholine is likely released rhythmically in the developing retina. Thus, starburst amacrine cells form the first identified network of retinal interneurons that directly participate in spontaneous rhythmic activities in the developing retina.}, Author = {Zhou, Z J}, Date-Added = {2013-08-14 14:43:31 +0000}, Date-Modified = {2013-08-14 14:44:20 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Rabbits; spontaneous activity; retina; visual system; activity-development; retinal waves; in vitro; Patch-Clamp Techniques}, Mesh = {Action Potentials; Animals; Cholinergic Fibers; Fluorescent Dyes; Isoquinolines; Patch-Clamp Techniques; Periodicity; Rabbits; Retina; Retinal Ganglion Cells; Synapses}, Month = {Jun}, Number = {11}, Pages = {4155-65}, pmid = {9592095}, Pst = {ppublish}, Title = {Direct participation of starburst amacrine cells in spontaneous rhythmic activities in the developing mammalian retina}, Volume = {18}, Year = {1998}} @article{Miller:1972, Author = {Miller, D J}, Date-Added = {2013-08-08 15:23:33 +0000}, Date-Modified = {2013-08-08 15:24:25 +0000}, Journal = {Child Dev}, Journal-Full = {Child development}, Keywords = {entrainment; development; human; infant; visual system; habituation; learning; memory}, Mesh = {Attention; Child Development; Color Perception; Fixation, Ocular; Form Perception; Habituation, Psychophysiologic; Humans; Infant; Male; Memory; Orientation; Probability; Visual Perception}, Month = {Jun}, Number = {2}, Pages = {481-93}, pmid = {5034730}, Pst = {ppublish}, Title = {Visual habituation in the human infant}, Volume = {43}, Year = {1972}, url = {papers/Miller_ChildDev1972.pdf}} @article{Lau:2008, Abstract = {BACKGROUND: Spatially mapped large scale gene expression databases enable quantitative comparison of data measurements across genes, anatomy, and phenotype. In most ongoing efforts to study gene expression in the mammalian brain, significant resources are applied to the mapping and visualization of data. This paper describes the implementation and utility of Brain Explorer, a 3D visualization tool for studying in situ hybridization-based (ISH) expression patterns in the Allen Brain Atlas, a genome-wide survey of 21,000 expression patterns in the C57BL\6J adult mouse brain. RESULTS: Brain Explorer enables users to visualize gene expression data from the C57Bl/6J mouse brain in 3D at a resolution of 100 microm3, allowing co-display of several experiments as well as 179 reference neuro-anatomical structures. Brain Explorer also allows viewing of the original ISH images referenced from any point in a 3D data set. Anatomic and spatial homology searches can be performed from the application to find data sets with expression in specific structures and with similar expression patterns. This latter feature allows for anatomy independent queries and genome wide expression correlation studies. CONCLUSION: These tools offer convenient access to detailed expression information in the adult mouse brain and the ability to perform data mining and visualization of gene expression and neuroanatomy in an integrated manner.}, Author = {Lau, Christopher and Ng, Lydia and Thompson, Carol and Pathak, Sayan and Kuan, Leonard and Jones, Allan and Hawrylycz, Mike}, Date-Added = {2013-08-08 12:55:28 +0000}, Date-Modified = {2013-08-08 12:56:11 +0000}, Doi = {10.1186/1471-2105-9-153}, Journal = {BMC Bioinformatics}, Journal-Full = {BMC bioinformatics}, Keywords = {neuroinformatics; visualization; technical report; Methods; Programming Languages; Software; Computational Biology; connectivity;}, Mesh = {Animals; Brain; Computer Graphics; Computer Simulation; Gene Expression; Gene Expression Profiling; Mice; Mice, Inbred C57BL; Models, Anatomic; Models, Biological; Nerve Tissue Proteins; Oligonucleotide Array Sequence Analysis; Software; Tissue Distribution; User-Computer Interface}, Pages = {153}, Pmc = {PMC2375125}, pmid = {18366675}, Pst = {epublish}, Title = {Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain}, Volume = {9}, Year = {2008}, url = {papers/Lau_BMCBioinformatics2008.pdf}} @article{Inamura:2011, Abstract = {Neuronal differentiation is a crucial event during neural development. Recent studies have characterized the development of the diencephalon; however, the origins of the primarily GABAergic prethalamic nuclei, including the zona incerta (ZI), ventral lateral geniculate nucleus (vLG) and reticular thalamic nucleus (RT), remain unclear. Here we characterize Olig2 lineage cells in the developing prethalamus using mice in which tamoxifen-induced recombination permanently labels Olig2-expressing cells. We show that GABAergic neurons in the prethalamic nuclei, including the RT, ZI and vLG, originate from prethalamic Olig2 lineage cells. Based on these data and on those derived from short-term lineage-tracing data using Olig3-lacZ mice and previous reports, we suggest that vLG cells originate from the ventricular zone of the thalamus, zona limitans intrathalamica and prethalamus.}, Author = {Inamura, Naoko and Ono, Katsuhiko and Takebayashi, Hirohide and Zalc, Bernard and Ikenaka, Kazuhiro}, Date-Added = {2013-08-07 13:38:36 +0000}, Date-Modified = {2013-08-07 13:39:45 +0000}, Doi = {10.1159/000328974}, Journal = {Dev Neurosci}, Journal-Full = {Developmental neuroscience}, Keywords = {development; visual system; thalamus; migration; Gene Expression; GABA; Interneurons}, Mesh = {Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Cell Lineage; Cell Movement; Female; GABAergic Neurons; Gene Expression Regulation, Developmental; Geniculate Bodies; Immunohistochemistry; In Situ Hybridization; Mice; Mice, Transgenic; Models, Animal; Nerve Tissue Proteins; Stem Cells; Subthalamus; Tamoxifen; Ventral Thalamic Nuclei}, Number = {2}, Pages = {118-29}, pmid = {21865661}, Pst = {ppublish}, Title = {Olig2 lineage cells generate GABAergic neurons in the prethalamic nuclei, including the zona incerta, ventral lateral geniculate nucleus and reticular thalamic nucleus}, Volume = {33}, Year = {2011}, url = {papers/Inamura_DevNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000328974}} @article{Arcelli:1997, Abstract = {The present study evaluated the occurrence, distribution, and number of GABAergic neurons in the thalamus of different mammalian species (bat, mouse, rat, guinea pig, rabbit, cat, monkey, humans), by means of light microscopical immunoenzymatic localization of GABA or of its biosynthetic enzyme glutamic acid decarboxylase and by ultrastructural immunogold detection of GABA. Our data demonstrated that: 1) GABAergic local circuit neurons were detected in the thalamic visual domain in all the species analyzed, whereas in other thalamic nuclei their presence and number varied among species; 2) the number of GABAergic local circuit neurons progressively increased in the dorsal thalamus of species with more complex behavior; 3) the presence of local circuit neurons conferred a similar intrinsic organization to the dorsal thalamic nuclei, characterized by complex synaptic arrangements; 4) in the reticular thalamic nucleus, whose neurons were GABA-immunoreactive in all the examined species, the cellular density decreased from the bat to humans. These findings strongly suggest that thalamic GABAergic local circuit neurons are not directly related to the ability to perform specific sensorimotor tasks, but they are likely to reflect an increasing complexity of the local information processing that occurs at thalamic level.}, Author = {Arcelli, P and Frassoni, C and Regondi, M C and De Biasi, S and Spreafico, R}, Date-Added = {2013-08-07 13:09:38 +0000}, Date-Modified = {2013-08-07 13:11:41 +0000}, Journal = {Brain Res Bull}, Journal-Full = {Brain research bulletin}, Keywords = {development; visual system; thalamus; Primates; rodent; GABA; interneurons}, Mesh = {Animals; Cats; Guinea Pigs; Mammals; Rabbits; Rats; Synapses; Thalamic Nuclei; Thalamus; gamma-Aminobutyric Acid}, Number = {1}, Pages = {27-37}, pmid = {8978932}, Pst = {ppublish}, Title = {GABAergic neurons in mammalian thalamus: a marker of thalamic complexity?}, Volume = {42}, Year = {1997}, url = {papers/Arcelli_BrainResBull1997.pdf}} @article{Rakic:2009, Abstract = {In the past three decades, mounting evidence has revealed that specification of the basic cortical neuronal classes starts at the time of their final mitotic divisions in the embryonic proliferative zones. This early cell determination continues during the migration of the newborn neurons across the widening cerebral wall, and it is in the cortical plate that they attain their final positions and establish species-specific cytoarchitectonic areas. Here, the development and evolutionary expansion of the neocortex is viewed in the context of the radial unit and protomap hypotheses. A broad spectrum of findings gave insight into the pathogenesis of cortical malformations and the biological bases for the evolution of the modern human neocortex. We examine the history and evidence behind the concept of early specification of neurons and provide the latest compendium of genes and signaling molecules involved in neuronal fate determination and specification.}, Author = {Rakic, Pasko and Ayoub, Albert E and Breunig, Joshua J and Dominguez, Martin H}, Date-Added = {2013-08-07 12:51:08 +0000}, Date-Modified = {2013-08-07 12:52:24 +0000}, Doi = {10.1016/j.tins.2009.01.007}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {review literature; Molecular Biology; Gene Expression; Cerebral Cortex; topographic map; Visual Cortex; visual system; patterning; development; Grants}, Mesh = {Animals; Body Patterning; Brain Mapping; Cell Movement; Cerebral Cortex; Gene Expression Regulation, Developmental; Humans; Models, Neurological; Neural Pathways; Neurogenesis; Neuronal Plasticity; Neurons}, Month = {May}, Number = {5}, Pages = {291-301}, Pmc = {PMC3601545}, pmid = {19380167}, Pst = {ppublish}, Title = {Decision by division: making cortical maps}, Volume = {32}, Year = {2009}, url = {papers/Rakic_TrendsNeurosci2009.pdf}} @article{Akrouh:2013, Abstract = {The developing retina generates spontaneous glutamatergic (stage III) waves of activity that sequentially recruit neighboring ganglion cells with opposite light responses (ON and OFF RGCs). This activity pattern is thought to help establish parallel ON and OFF pathways in downstream visual areas. The circuits that produce stage III waves and desynchronize ON and OFF RGC firing remain obscure. Using dual patch-clamp recordings, we find that ON and OFF RGCs receive sequential excitatory input from ON and OFF cone bipolar cells (CBCs), respectively. This input sequence is generated by crossover circuits, in which ON CBCs control glutamate release from OFF CBCs via diffusely stratified inhibitory amacrine cells. In addition, neighboring ON CBCs communicate directly and indirectly through lateral glutamatergic transmission and gap junctions, both of which are required for wave initiation and propagation. Thus, intersecting lateral excitatory and vertical inhibitory circuits give rise to precisely patterned stage III retinal waves.}, Author = {Akrouh, Alejandro and Kerschensteiner, Daniel}, Date-Added = {2013-07-15 14:14:55 +0000}, Date-Modified = {2013-08-28 14:10:43 +0000}, Doi = {10.1016/j.neuron.2013.05.012}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {retinal waves; spontaneous activity; development; retina; Retinal Ganglion Cells; bipolar cells; currOpinRvw}, Month = {Jul}, pmid = {23830830}, Pst = {aheadofprint}, Title = {Intersecting Circuits Generate Precisely Patterned Retinal Waves}, Year = {2013}, url = {papers/Akrouh_Neuron2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2013.05.012}} @article{Rivlin-Etzion:2012, Abstract = {Direction selectivity in the retina is mediated by direction-selective ganglion cells. These cells are part of a circuit in which they are asymmetrically wired to inhibitory neurons. Thus, they respond strongly to an image moving in the preferred direction and weakly to an image moving in the opposite (null) direction. Here, we demonstrate that adaptation with short visual stimulation of a direction-selective ganglion cell using drifting gratings can reverse this cell's directional preference by 180$\,^{\circ}$. This reversal is robust, long lasting, and independent of the animal's age. Our findings indicate that, even within circuits that are hardwired, the computation of direction can be altered by dynamic circuit mechanisms that are guided by visual stimulation.}, Author = {Rivlin-Etzion, Michal and Wei, Wei and Feller, Marla B}, Date-Added = {2013-07-15 14:13:03 +0000}, Date-Modified = {2013-07-15 14:14:03 +0000}, Doi = {10.1016/j.neuron.2012.08.041}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Retina; development; Retinal Ganglion Cells; direction; topographic map; neurophysiology; inhibition}, Mesh = {Adaptation, Physiological; Animals; Female; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motion Perception; Photic Stimulation; Reaction Time; Retinal Ganglion Cells}, Month = {Nov}, Number = {3}, Pages = {518-25}, Pmc = {PMC3496185}, pmid = {23141064}, Pst = {ppublish}, Title = {Visual stimulation reverses the directional preference of direction-selective retinal ganglion cells}, Volume = {76}, Year = {2012}, url = {papers/Rivlin-Etzion_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.08.041}} @article{Gitton:1999, Abstract = {In the H-2Z1 mouse line, postnatal expression of the lacZ containing transgene in the cerebral cortex is restricted to layer IV neurons of the somatosensory area. We have used H-2Z1 embryos in previous heterotopic transplantation experiments to investigate the chronology of determination of areal identity. From the onset of neurogenesis, the cortex was regionalized in domains fated to express or not the somatosensory area-specific transgene. Determination occured 1 day later. In the present study, we show that, in vivo, H-2Z1 expression coincides with invasion of the cortical plate by thalamic afferents. We therefore investigated the role of thalamic innervation in the onset of H-2Z1 expression. For this purpose, we examined the pattern of H-2Z1 expression in perinatal cortical explant, in reeler mutant and MaoA deficient mice, or in animals which had received neonatal lesions affecting the somatosensory cortex or the thalamocortical projection. We found that, around birth, a switch occurs in the control of H-2Z1 expression: whereas H-2Z1 expression developed autonomously in embryonic parietal cortex in the absence of thalamic fibers, a transient requirement for a thalamic axon derived signal was observed postnatally. This property has interesting implications for the plasticity of cortical areas in development and evolution.}, Author = {Gitton, Y and Cohen-Tannoudji, M and Wassef, M}, Date-Added = {2013-07-15 14:11:08 +0000}, Date-Modified = {2013-07-15 14:12:10 +0000}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {genes; technique; ideas; Thalamic Nuclei; marker; Somatosensory Cortex; mouse; development; Neocortex;}, Mesh = {Animals; Animals, Newborn; Axons; Biological Markers; Cells, Cultured; Denervation; Female; Gene Expression Regulation, Developmental; Gene Expression Regulation, Enzymologic; Genes, Reporter; Lac Operon; Lip; Male; Mice; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Neurologic Mutants; Mice, Transgenic; Monoamine Oxidase; Neural Pathways; Parietal Lobe; Somatosensory Cortex; Thalamus; Transgenes; beta-Galactosidase}, Month = {Sep}, Number = {6}, Pages = {611-20}, pmid = {10498279}, Pst = {ppublish}, Title = {Role of thalamic axons in the expression of H-2Z1, a mouse somatosensory cortex specific marker}, Volume = {9}, Year = {1999}, url = {papers/Gitton_CerebCortex1999.pdf}} @article{Song:2005a, Abstract = {The oocyte is a highly differentiated cell. It makes organelles specialized to its unique functions and progresses through a series of developmental stages to acquire a fertilization competent phenotype. This review will integrate the biology of the oocyte with what is known about oocyte-specific gene regulation and transcription factors involved in oocyte development. We propose that oogenesis is reliant on a dynamic gene regulatory network that includes oocyte-specific transcriptional regulators.}, Author = {Song, Jia L and Wessel, Gary M}, Date-Added = {2013-07-05 21:11:54 +0000}, Date-Modified = {2013-07-05 21:13:06 +0000}, Doi = {10.1111/j.1432-0436.2005.07301005.x}, Journal = {Differentiation}, Journal-Full = {Differentiation; research in biological diversity}, Keywords = {development; Transcription; gene; Environment; Regeneration; Stem Cells}, Mesh = {Animals; Basic Helix-Loop-Helix Transcription Factors; DNA-Binding Proteins; Female; Gene Expression Regulation, Developmental; Homeodomain Proteins; Humans; Octamer Transcription Factor-3; Oocytes; Oogenesis; Organ Specificity; Ovary; Ovum; Pregnancy; RNA, Ribosomal; Transcription Factors; Transcription, Genetic; Xenopus Proteins}, Month = {Feb}, Number = {1}, Pages = {1-17}, pmid = {15733063}, Pst = {ppublish}, Title = {How to make an egg: transcriptional regulation in oocytes}, Volume = {73}, Year = {2005}, url = {papers/Song_Differentiation2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1432-0436.2005.07301005.x}} @article{Dimos:2008, Abstract = {The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell types affected by that patient's disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. We have generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.}, Author = {Dimos, John T and Rodolfa, Kit T and Niakan, Kathy K and Weisenthal, Laurin M and Mitsumoto, Hiroshi and Chung, Wendy and Croft, Gist F and Saphier, Genevieve and Leibel, Rudy and Goland, Robin and Wichterle, Hynek and Henderson, Christopher E and Eggan, Kevin}, Date-Added = {2013-07-05 20:54:00 +0000}, Date-Modified = {2013-07-05 21:11:18 +0000}, Doi = {10.1126/science.1158799}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Stem Cells; Pluripotent Stem Cells; development; gene; Regeneration}, Mesh = {Aged, 80 and over; Amyotrophic Lateral Sclerosis; Cell Differentiation; Cell Line; Embryonic Stem Cells; Female; Fibroblasts; Gene Expression; Humans; Motor Neurons; Neuroglia; Nuclear Reprogramming; Pluripotent Stem Cells; Retroviridae; Spinal Cord; Superoxide Dismutase; Transcription Factors; Transduction, Genetic}, Month = {Aug}, Number = {5893}, Pages = {1218-21}, pmid = {18669821}, Pst = {ppublish}, Title = {Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons}, Volume = {321}, Year = {2008}, url = {papers/Dimos_Science2008.pdf}} @article{King:2000, Abstract = {Many animals with laterally placed eyes, such as chameleons, move their eyes independently of one another. In contrast, primates with frontally placed eyes and binocular vision must move them together so that both eyes are aimed at the same point in visual space. Is binocular coordination an innate feature of how our brains are wired, or have we simply learned to move our eyes together? This question sparked a controversy in the 19(th) century between two eminent German scientists, Ewald Hering and Hermann von Helmholtz. Hering took the position that binocular coordination was innate and vigorously challenged von Helmholtz's view that it was learned. Hering won the argument and his hypothesis, known as Hering's Law of Equal Innervation, became generally accepted. New evidence suggests, however, that similar to chameleons, primates may program movements of each eye independently. Binocular coordination is achieved by a neural network at the motor periphery comprised of motoneurons and specialized interneurons located near or in the cranial nerve nuclei that innervate the extraocular muscles. It is assumed that this network must be trained and calibrated during infancy and probably throughout life in order to maintain the precise binocular coordination characteristic of primate eye movements despite growth, aging effects, and injuries to the eye movement neuromuscular system. Malfunction of this network or its ability to adaptively learn may be a contributing cause of strabismus.}, Author = {King, W M and Zhou, W}, Date-Added = {2013-07-01 21:14:53 +0000}, Date-Modified = {2013-07-01 21:15:50 +0000}, Journal = {Anat Rec}, Journal-Full = {The Anatomical record}, Keywords = {currOpinRvw; Activity-development; visual system; motor; Saccades; binocular disparity; mirror symmetry}, Mesh = {Animals; Eye Movements; Lizards; Motor Neurons; Oculomotor Muscles; Primates; Strabismus; Vision, Binocular}, Month = {Aug}, Number = {4}, Pages = {153-61}, pmid = {10944576}, Pst = {ppublish}, Title = {New ideas about binocular coordination of eye movements: is there a chameleon in the primate family tree?}, Volume = {261}, Year = {2000}, url = {papers/King_AnatRec2000.pdf}} @article{Medina:2000, Abstract = {Recent data on the expression of several homeobox genes in the embryonic telencephalon of mammals, birds and reptiles support the homology of a part of the avian pallium, named the Wulst, and at least the more-medial and superior parts of mammalian neocortex. This conclusion is also supported by previous embryological, topological and hodological data. Furthermore, new evidence on the connections and electrophysiological properties of specific subfields within the avian Wulst, and on the thalamic territories that project to these fields, supports the more-specific conclusion that a primary visual area and a primary somatosensory-somatomotor area are present in the avian Wulst; these areas are likely to be homologous to their counterparts in mammals. In spite of this, developmental, morphological and comparative evidence indicate that some structural and physiological traits that appear to be similar in the Wulst and neocortex (such as the lamination or binocularity) evolved independently in birds and mammals.}, Author = {Medina, L and Reiner, A}, Date-Added = {2013-06-14 18:49:31 +0000}, Date-Modified = {2013-06-14 18:50:50 +0000}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {neocortex; cerebral cortex; turtle; Evolution; Visual Cortex; birds; reptiles; mammals; review literature}, Mesh = {Animals; Biological Evolution; Birds; Brain; Gene Expression Regulation; Genes, Homeobox; Mammals; Models, Neurological; Neocortex; Nerve Net; Species Specificity}, Month = {Jan}, Number = {1}, Pages = {1-12}, pmid = {10631781}, Pst = {ppublish}, Title = {Do birds possess homologues of mammalian primary visual, somatosensory and motor cortices?}, Volume = {23}, Year = {2000}, url = {papers/Medina_TrendsNeurosci2000.pdf}} @article{Mulligan:1990, Abstract = {The projection from the dorsal lateral geniculate complex to the visual cortex in Pseudemys and Chrysemys turtles was examined by using the anterograde transport of horseradish peroxidase (HRP) in vitro and the retrograde transport of HRP in vivo. In vitro HRP injections into the lateral forebrain bundle were used to fill geniculocortical axons anterogradely, which were then analyzed in cortical wholemount preparations. Geniculocortical axons gain access to the visual cortex along its entire rostral-caudal extent. They course in slightly curved trajectories for up to 2 mm from the lateral edge of the cortex through both the lateral (or pallial thickening) and medial parts of Desan's cortical area D2. Single axons are of fine caliber. They tend to cross each other and sometimes branch in the pallial thickening, but are generally unbranched in the medial part of D2. They bear small, fusiform varicosities at irregular intervals along their lengths. Although axons show small variations in the number of varicosities per 100 microns segment, no consistent variation in varicosity number as a function of distance could be detected. These results indicate that geniculocortical axons project to the visual cortex in an orderly pattern. The retrograde transport experiments provide some clue as to the significance of this pattern. Small, ionotophoretic injections of HRP in the visual cortex retrogradely labeled neurons in the dorsal lateral geniculate complex. Injections in the rostral visual cortex retrogradely labeled neurons in the caudal pole of the geniculate complex. Injections at progressively more caudal loci within the visual cortex labeled neurons at progressively more rostral loci within the geniculate complex. Thus, there is a representation of the rostral-caudal axis of the geniculate complex along the caudal-rostral axis of the visual cortex. Consistent with the anterograde transport experiments that showed individual geniculocortical axons coursing through both lateral and medial parts of the visual cortex, HRP injections restricted to the medial edge of the visual cortex retrogradely labeled neurons along the entire dorsal-ventral axis of the geniculate complex at the appropriate rostral-caudal position. The neurophysiological studies of Mazurskaya ('72: J. Evol. Biochem. Physiol. 8:550-555; respond to a small, moving stimulus anywhere in visual space, implying a convergence of inputs from all points in visual space somewhere along the retinogeniculocortical pathway. The experiments reported here suggest a convergence in the geniculocortical projections of information along the vertical meridians, or azimuth lines, of visual space onto neurons lying along lateral to medial transects through the visual cortex.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Mulligan, K A and Ulinski, P S}, Date-Added = {2013-06-14 16:44:25 +0000}, Date-Modified = {2013-06-14 16:50:21 +0000}, Doi = {10.1002/cne.902960403}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {Visual Cortex; Turtles; in vivo; visual system; topographic map; Anatomy; connectivity; Histocytochemistry; tracer}, Mesh = {Animals; Geniculate Bodies; Horseradish Peroxidase; Nerve Endings; Turtles; Visual Cortex; Visual Pathways}, Month = {Jun}, Number = {4}, Pages = {531-47}, pmid = {2358551}, Pst = {ppublish}, Title = {Organization of geniculocortical projections in turtles: isoazimuth lamellae in the visual cortex}, Volume = {296}, Year = {1990}, url = {papers/Mulligan_JCompNeurol1990a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902960403}} @article{Cosans:1990, Abstract = {The spatial pattern of projections within turtle visual cortex was studied by using focal injections of horseradish peroxidase into visual cortex in an in vitro wholebrain preparation. Injections anterogradely filled the axons of many layer 2 neurons, which could be followed for 200-500 microns from the injection sites. Axons were typically unbranched, relatively straight, and bore small varicosities at irregular intervals. They radiated from the injection sites in all directions, but showed some preference toward orientations along the lateral-medial axis of the cortex. Earlier work (Mulligan and Ulinski, '90) had demonstrated that turtle visual cortex contains a series of isoazimuth lamellae, each representing an individual azimuth of visual space and oriented perpendicular to the rostral-caudal axis of the cortex. The present study provides evidence for intrinsic projections both along isoazimuth lamellae and between adjacent lamellae. These projections may play roles in the elaboration of wide receptive fields of cortical neurons.}, Author = {Cosans, C E and Ulinski, P S}, Date-Added = {2013-06-14 16:44:21 +0000}, Date-Modified = {2013-06-14 16:46:30 +0000}, Doi = {10.1002/cne.902960404}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {Visual Cortex; Turtles; in vivo; visual system; topographic map; Anatomy; connectivity}, Mesh = {Animals; Axons; Horseradish Peroxidase; Turtles; Visual Cortex}, Month = {Jun}, Number = {4}, Pages = {548-58}, pmid = {2358552}, Pst = {ppublish}, Title = {Spatial organization of axons in turtle visual cortex: intralamellar and interlamellar projections}, Volume = {296}, Year = {1990}, url = {papers/Cosans_JCompNeurol1990.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902960404}} @article{Schutte:1995, Abstract = {Centrifugal fibers innervating the retina have been shown in all classes of vertebrate, except for mammals where conventional tract-tracing methods have not been able to unmistakably demonstrate their existence. In a previous study, a unilateral, intravitreal injection of 5,7-dihydroxytryptamine was used to reveal indoleamine-accumulating centrifugal fibers which were visualized by an immunoreaction against serotonin. In the present study, I employed a modification of this method to stain retinopetal neurons in the rat. Terminals were located preferentially in the outer retina; labeled fibers could be traced back along an ipsilateral pathway to somata in the dorso-caudal portions of the chiasm or the medio-lateral preoptic area, and thence towards the suprachiasmatic nuclei. The unique beaded appearance of the fibers distinguishes them from retinal ganglion cell axons. The labeling of central cell bodies strongly suggests that they possess terminals in the retina. Thus, at least some mammalian retinas receive centrifugal innervation. This indoleamine-accumulating retinopetal pathway may be involved in retinal melatonin synthesis, coordination of circadian rhythms, and interocular phenomena.}, Author = {Sch{\"u}tte, M}, Date = {1995 Nov-Dec}, Date-Added = {2013-06-14 16:17:23 +0000}, Date-Modified = {2013-06-14 16:19:16 +0000}, Journal = {Vis Neurosci}, Journal-Full = {Visual neuroscience}, Keywords = {retinopetal; retino-retinal; retino-retino; connectivity; visual system; Serotonin; retina; mirror symmetry; Binocular;}, Mesh = {5,7-Dihydroxytryptamine; Animals; Immunologic Techniques; Male; Nerve Fibers; Neurons; Optic Nerve; Preoptic Area; Rats; Rats, Inbred Strains; Retina; Serotonin; Suprachiasmatic Nucleus; Visual Pathways}, Number = {6}, Pages = {1083-92}, pmid = {8962828}, Pst = {ppublish}, Title = {Centrifugal innervation of the rat retina}, Volume = {12}, Year = {1995}, url = {papers/Schütte_VisNeurosci1995.pdf}} @article{Ulinski:1988, Abstract = {Organization of retinal projections to the dorsal lateral geniculate complex in turtles has been studied by means of light and electron microscopic axon tracing techniques. Orthograde degeneration studies with Fink-Heimer methods following restricted retinal lesions show the entire retina has a topologically organized projection to the contralateral dorsal lateral geniculate complex. The nasotemporal axis of the retina projects along the rostrocaudal axis of the geniculate complex; the dorsoventral axis of the retina projects along the dorsoventral axis of the geniculate complex. The projection to the ipsilateral dorsal lateral geniculate complex originates from the ventral, temporal and nasal edges of the retina. The nasotemporal axis of the ipsilateral retina projects along the rostrocaudal axis of the geniculate complex. It was not possible to determine the orientation of the dorsoventral axis of the ipsilateral retina on the geniculate complex. Light microscopic autoradiographic tracing experiments and electron microscopic degeneration experiments show the retinogeniculate projection has a laminar organization. Retinogeniculate terminals are found in both the neuropile and cell plate throughout all three subnuclei of the dorsal lateral geniculate complex but have a distinctive distribution in each subnucleus. In the subnucleus ovalis, they are frequent in both the neuropile and cell plate which forms the rostral pole of the complex. In the dorsal subnucleus, they are most prevalent in the outer part of the neuropile layer, less frequent in the inner part of the neuropile, and rare in the cell plate. In the ventral subnucleus, they are frequent in the outer part of the neuropile but are also common in the inner part of the neuropile and cell plate. These observations point to several principles of geniculate organization in turtles. First, the complex receives projections from the entire contralateral retina and a segment of the ipsilateral retina. It thus has monocular and binocular segments that together receive a topologically organized representation of the binocular visual space and the contralateral monocular visual space. Second, the three geniculate subnuclei receive information from different, specialized regions of the retina and visual space. Subnucleus ovalis receives information from the frontal binocular visual field. The ventral subnucleus receives information from the caudal binocular field. The dorsal subnucleus receives input from the contralateral monocular field. Third, there is a lamination of retinal inputs in the geniculate complex which differs in character within the three subnuclei.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Ulinski, P S and Nautiyal, J}, Date-Added = {2013-06-14 16:07:31 +0000}, Date-Modified = {2013-06-14 16:08:38 +0000}, Doi = {10.1002/cne.902760107}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {turtle; anatomy; connectivity; topographic map; visual system; LGN; retina; Visual Cortex;}, Mesh = {Animals; Functional Laterality; Geniculate Bodies; Microscopy, Electron; Nerve Degeneration; Nerve Endings; Retina; Turtles; Visual Pathways}, Month = {Oct}, Number = {1}, Pages = {92-112}, pmid = {3192765}, Pst = {ppublish}, Title = {Organization of retinogeniculate projections in turtles of the genera Pseudemys and Chrysemys}, Volume = {276}, Year = {1988}, url = {papers/Ulinski_JCompNeurol1988.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902760107}} @article{Warren:2008, Abstract = {We present a draft genome sequence of the platypus, Ornithorhynchus anatinus. This monotreme exhibits a fascinating combination of reptilian and mammalian characters. For example, platypuses have a coat of fur adapted to an aquatic lifestyle; platypus females lactate, yet lay eggs; and males are equipped with venom similar to that of reptiles. Analysis of the first monotreme genome aligned these features with genetic innovations. We find that reptile and platypus venom proteins have been co-opted independently from the same gene families; milk protein genes are conserved despite platypuses laying eggs; and immune gene family expansions are directly related to platypus biology. Expansions of protein, non-protein-coding RNA and microRNA families, as well as repeat elements, are identified. Sequencing of this genome now provides a valuable resource for deep mammalian comparative analyses, as well as for monotreme biology and conservation.}, Author = {Warren, Wesley C and Hillier, LaDeana W and Marshall Graves, Jennifer A and Birney, Ewan and Ponting, Chris P and Gr{\"u}tzner, Frank and Belov, Katherine and Miller, Webb and Clarke, Laura and Chinwalla, Asif T and Yang, Shiaw-Pyng and Heger, Andreas and Locke, Devin P and Miethke, Pat and Waters, Paul D and Veyrunes, Fr{\'e}d{\'e}ric and Fulton, Lucinda and Fulton, Bob and Graves, Tina and Wallis, John and Puente, Xose S and L{\'o}pez-Ot{\'\i}n, Carlos and Ord{\'o}{\~n}ez, Gonzalo R and Eichler, Evan E and Chen, Lin and Cheng, Ze and Deakin, Janine E and Alsop, Amber and Thompson, Katherine and Kirby, Patrick and Papenfuss, Anthony T and Wakefield, Matthew J and Olender, Tsviya and Lancet, Doron and Huttley, Gavin A and Smit, Arian F A and Pask, Andrew and Temple-Smith, Peter and Batzer, Mark A and Walker, Jerilyn A and Konkel, Miriam K and Harris, Robert S and Whittington, Camilla M and Wong, Emily S W and Gemmell, Neil J and Buschiazzo, Emmanuel and Vargas Jentzsch, Iris M and Merkel, Angelika and Schmitz, Juergen and Zemann, Anja and Churakov, Gennady and Kriegs, Jan Ole and Brosius, Juergen and Murchison, Elizabeth P and Sachidanandam, Ravi and Smith, Carly and Hannon, Gregory J and Tsend-Ayush, Enkhjargal and McMillan, Daniel and Attenborough, Rosalind and Rens, Willem and Ferguson-Smith, Malcolm and Lef{\`e}vre, Christophe M and Sharp, Julie A and Nicholas, Kevin R and Ray, David A and Kube, Michael and Reinhardt, Richard and Pringle, Thomas H and Taylor, James and Jones, Russell C and Nixon, Brett and Dacheux, Jean-Louis and Niwa, Hitoshi and Sekita, Yoko and Huang, Xiaoqiu and Stark, Alexander and Kheradpour, Pouya and Kellis, Manolis and Flicek, Paul and Chen, Yuan and Webber, Caleb and Hardison, Ross and Nelson, Joanne and Hallsworth-Pepin, Kym and Delehaunty, Kim and Markovic, Chris and Minx, Pat and Feng, Yucheng and Kremitzki, Colin and Mitreva, Makedonka and Glasscock, Jarret and Wylie, Todd and Wohldmann, Patricia and Thiru, Prathapan and Nhan, Michael N and Pohl, Craig S and Smith, Scott M and Hou, Shunfeng and Nefedov, Mikhail and de Jong, Pieter J and Renfree, Marilyn B and Mardis, Elaine R and Wilson, Richard K}, Date-Added = {2013-06-13 15:43:25 +0000}, Date-Modified = {2013-06-13 15:43:25 +0000}, Doi = {10.1038/nature06936}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Animals; Base Composition; Dentition; Evolution, Molecular; Female; Genome; Genomic Imprinting; Humans; Immunity; Male; Mammals; MicroRNAs; Milk Proteins; Phylogeny; Platypus; Receptors, Odorant; Repetitive Sequences, Nucleic Acid; Reptiles; Sequence Analysis, DNA; Spermatozoa; Venoms; Zona Pellucida}, Month = {May}, Number = {7192}, Pages = {175-83}, Pmc = {PMC2803040}, pmid = {18464734}, Pst = {ppublish}, Title = {Genome analysis of the platypus reveals unique signatures of evolution}, Volume = {453}, Year = {2008}, url = {papers/Warren_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06936}} @article{Hall:1970, Abstract = {The telencephalic projections of the turtle thalamus were studied using the Fink-Heimer ('67) technique for staining dezenerated axons and their terminals. Large thalamic lesions produced terminal degeneration in the basal telencephalic nuclei, the core of the dorsal ventricular ridge and the outer half of layer I in general cortex. A variety of control lesions confirmed that these projections arisc in the thalamus. Circumscribed thalamic lesions revealed first, that there is some degree of spatial organization in the turtlc's thalamocortical projection system and second, that at least one sensory relay nucleus, the dorsal lateral geniculate, projects to general cortex. Detailed comparisons of the turtle's thalamotelencephalic projections with thosc present in two primitive mammalian species, the hedgehog and the opos- sum, provided a basis for identifying probablc homologies in thc forebrains of reptilcs and mnmmals.}, Author = {Hall, W C and Ebner, F F}, Date-Added = {2013-06-12 19:25:55 +0000}, Date-Modified = {2013-06-12 19:27:40 +0000}, Doi = {10.1002/cne.901400107}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {turtle; Visual Cortex; anatomy; LGN; thalamus; connectivity; Histological Techniques; Classical; projection; topographic map}, Mesh = {Anatomy, Comparative; Animals; Cerebral Cortex; Geniculate Bodies; Insectivora; Nerve Degeneration; Neural Pathways; Opossums; Telencephalon; Thalamus; Turtles}, Month = {Sep}, Number = {1}, Pages = {101-22}, pmid = {5459208}, Pst = {ppublish}, Title = {Thalamotelencephalic projections in the turtle (Pseudemys scripta)}, Volume = {140}, Year = {1970}, url = {papers/Hall_JCompNeurol1970.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901400107}} @article{Prechtl:1997, Abstract = {The computations involved in the processing of a visual scene invariably involve the interactions among neurons throughout all of visual cortex. One hypothesis is that the timing of neuronal activity, as well as the amplitude of activity, provides a means to encode features of objects. The experimental data from studies on cat [Gray, C. M., Konig, P., Engel, A. K. & Singer, W. (1989) Nature (London) 338, 334-337] support a view in which only synchronous (no phase lags) activity carries information about the visual scene. In contrast, theoretical studies suggest, on the one hand, the utility of multiple phases within a population of neurons as a means to encode independent visual features and, on the other hand, the likely existence of timing differences solely on the basis of network dynamics. Here we use widefield imaging in conjunction with voltage-sensitive dyes to record electrical activity from the virtually intact, unanesthetized turtle brain. Our data consist of single-trial measurements. We analyze our data in the frequency domain to isolate coherent events that lie in different frequency bands. Low frequency oscillations (<5 Hz) are seen in both ongoing activity and activity induced by visual stimuli. These oscillations propagate parallel to the afferent input. Higher frequency activity, with spectral peaks near 10 and 20 Hz, is seen solely in response to stimulation. This activity consists of plane waves and spiral-like waves, as well as more complex patterns. The plane waves have an average phase gradient of approximately pi/2 radians/mm and propagate orthogonally to the low frequency waves. Our results show that large-scale differences in neuronal timing are present and persistent during visual processing.}, Author = {Prechtl, J C and Cohen, L B and Pesaran, B and Mitra, P P and Kleinfeld, D}, Date-Added = {2013-06-12 18:57:37 +0000}, Date-Modified = {2013-06-12 18:59:50 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {turtle; voltage sensor; optical imaging; optical physiology; neurophysiology; in vivo; visual cortex; next}, Mesh = {Animals; Cats; Cerebral Cortex; Electrophysiology; Photic Stimulation; Turtles; Vision, Ocular}, Month = {Jul}, Number = {14}, Pages = {7621-6}, Pmc = {PMC23872}, pmid = {9207142}, Pst = {ppublish}, Title = {Visual stimuli induce waves of electrical activity in turtle cortex}, Volume = {94}, Year = {1997}, url = {papers/Prechtl_ProcNatlAcadSciUSA1997.pdf}} @article{Rutishauser:2013, Abstract = {Brain activity often consists of interactions between internal-or on-going-and external-or sensory-activity streams, resulting in complex, distributed patterns of neural activity. Investigation of such interactions could benefit from closed-loop experimental protocols in which one stream can be controlled depending on the state of the other. We describe here methods to present rapid and precisely timed visual stimuli to awake animals, conditional on features of the animal's on-going brain state; those features are the presence, power and phase of oscillations in local field potentials (LFP). The system can process up to 64 channels in real time. We quantified its performance using simulations, synthetic data and animal experiments (chronic recordings in the dorsal cortex of awake turtles). The delay from detection of an oscillation to the onset of a visual stimulus on an LCD screen was 47.5ms and visual-stimulus onset could be locked to the phase of ongoing oscillations at any frequency ≤40Hz. Our software's architecture is flexible, allowing on-the-fly modifications by experimenters and the addition of new closed-loop control and analysis components through plugins. The source code of our system "StimOMatic" is available freely as open-source.}, Author = {Rutishauser, Ueli and Kotowicz, Andreas and Laurent, Gilles}, Date-Added = {2013-06-12 18:44:04 +0000}, Date-Modified = {2013-06-12 18:50:44 +0000}, Doi = {10.1016/j.jneumeth.2013.02.020}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {technique; Methods; next; neurophysiology; hardware; Programming Languages; visual system; in vivo; Electrophysiology}, Month = {Apr}, Number = {1}, Pages = {139-55}, pmid = {23473800}, Pst = {ppublish}, Title = {A method for closed-loop presentation of sensory stimuli conditional on the internal brain-state of awake animals}, Volume = {215}, Year = {2013}, url = {papers/Rutishauser_JNeurosciMethods2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2013.02.020}} @article{Kriegstein:1986, Abstract = {We have examined the synaptic physiology of the isolated dorsal cortex of the turtle, Pseudemys scripta elegans. Electrical stimulation of afferent pathways elicited distinct, stereotyped responses in pyramidal and stellate neurons. Single shocks evoked a long-lasting barrage of excitatory postsynaptic potentials (EPSPs) in stellate cells, and led to a burst of several action potentials. Under the same circumstances, pyramidal cells displayed a small amount of short-latency excitation, but this was accompanied by a profound and prolonged set of inhibitory post-synaptic potentials (IPSPs). Synaptic excitation of the distal dendrites of pyramidal cells could evoke dendritic action potentials that were visible at the soma as small all-or-none spikes rising from the hyperpolarized level of the IPSP. There appeared to be two mechanistically different types of IPSPs in pyramidal cells. The first occurred at short latency, could produce a very large conductance increase, reversed polarity at -71 mV, and was chloride-dependent. The second was generally smaller and more protracted, had a relatively negative reversal potential of -85 to -95 mV, and was insensitive to chloride injection. Focal application of small doses of the putative inhibitory neurotransmitter gamma-aminobutyric acid (GABA) onto the somata of pyramidal cells caused a conductance increase and hyperpolarization. This response had features in common with the short-latency IPSP, including an identical reversal potential. Application of large doses of GABA to the somata of pyramidal cells or smaller doses to their dendrites elicited multiphasic or purely depolarizing responses that were at least partly due to time- or space-dependent shifts of the equilibrium potential of the response. Bicuculline methiodide, a potent GABA antagonist, depressed both the responses to GABA and the short-latency IPSP, but not the long-latency IPSP; synchronized epileptiform burst discharges also resulted. These findings, together with responses to locally applied electric shocks and the excitatory amino acid glutamate, suggested that inhibition of pyramidal cells was generated intrinsically by stellate cells, and that the cortical circuit provides pathways for both feedforward and feedback GABAergic inhibition. The data also suggest that pyramidal cells are mutually excitatory. These features are similar to the basic intrinsic circuitry in the telencephalic cortices of mammals.}, Author = {Kriegstein, A R and Connors, B W}, Date-Added = {2013-06-12 18:38:19 +0000}, Date-Modified = {2013-06-12 18:39:23 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {neurophysiology; Patch-Clamp Techniques; Turtles; physiology; Synapses; Visual Cortex}, Mesh = {Animals; Bicuculline; Chlorides; Electrophysiology; Evoked Potentials; Glutamates; Glutamic Acid; Intracellular Fluid; Membrane Potentials; Pyramidal Tracts; Synapses; Turtles; Visual Cortex; gamma-Aminobutyric Acid}, Month = {Jan}, Number = {1}, Pages = {178-91}, pmid = {2868076}, Pst = {ppublish}, Title = {Cellular physiology of the turtle visual cortex: synaptic properties and intrinsic circuitry}, Volume = {6}, Year = {1986}, url = {papers/Kriegstein_JNeurosci1986.pdf}} @article{Wu:2008, Abstract = {The development of voltage-sensitive dyes (VSD) and fast optical imaging techniques have brought us a new tool for examining spatiotemporal patterns of population neuronal activity in the neocortex. Propagating waves have been observed during almost every type of cortical processing examined by VSD imaging or electrode arrays. These waves provide subthreshold depolarization to individual neurons and increase their spiking probability. Therefore, the propagation of the waves sets up a spatiotemporal framework for increased excitability in neuronal populations, which can help to determine when and where the neurons are likely to fire. In this review, first discussed is propagating waves observed in various systems and possible mechanisms for generating and sustaining these waves. Then discussed are wave dynamics as an emergent behavior of the population activity that can, in turn, influence the activity of individual neurons. The functions of spontaneous and sensory-evoked waves remain to be explored. An important next step will be to examine the interaction between dynamics of propagating waves and functions in the cortex, and to verify if cortical processing can be modified when these waves are altered.}, Author = {Wu, Jian-Young and Xiaoying Huang and Chuan Zhang}, Date-Added = {2013-06-12 18:28:17 +0000}, Date-Modified = {2013-06-12 18:29:40 +0000}, Doi = {10.1177/1073858408317066}, Journal = {Neuroscientist}, Journal-Full = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, Keywords = {waves; Visual Cortex; visual system; optical imaging; neurophysiology; voltage sensor; review literature}, Mesh = {Action Potentials; Animals; Electrophysiology; Evoked Potentials; Fluorescent Dyes; Humans; Neocortex; Nerve Net; Neural Pathways; Neurons; Optics and Photonics; Sensory Receptor Cells}, Month = {Oct}, Number = {5}, Pages = {487-502}, Pmc = {PMC2679998}, pmid = {18997124}, Pst = {ppublish}, Title = {Propagating waves of activity in the neocortex: what they are, what they do}, Volume = {14}, Year = {2008}, url = {papers/Wu_Neuroscientist2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1177/1073858408317066}} @article{Senseman:1999, Abstract = {The network behavior of cortical cells during the processing of a light flash was characterized in an isolated, but functionally intact, turtle visual system. Rapid changes in intracellular membrane potential were monitored optically using a voltage-sensitive dye (VSD). Spatially coherent changes in membrane potential were determined by subjecting high-speed movies of the VSD signals to Karhunen-Lo{\'e}ve decomposition. In all experimental trials analyzed (n > 50), coherent activity was restricted to a small number of similar spatial patterns or modes. At least four modes (M(1,1), M(1,2), M(2,1), and M(2,2)) have an organizational structure similar to the normal modes of a vibrating membrane (drum). This empirical observation of modal activity provides a useful framework for analyzing the macroscopic behavior of cortical networks.}, Author = {Senseman, D M and Robbins, K A}, Date-Added = {2013-06-12 18:23:26 +0000}, Date-Modified = {2013-06-12 18:25:41 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Turtles; Visual Cortex; waves; neurophysiology; optical imaging; voltage sensor; Computational Biology; Computer Simulation; technique; next}, Mesh = {Animals; Cerebral Cortex; Evoked Potentials, Visual; Mathematics; Membrane Potentials; Models, Neurological; Nerve Net; Photic Stimulation; Turtles; Visual Perception}, Month = {May}, Number = {10}, Pages = {RC3}, pmid = {10234049}, Pst = {ppublish}, Title = {Modal behavior of cortical neural networks during visual processing}, Volume = {19}, Year = {1999}, url = {papers/Senseman_JNeurosci1999.pdf}} @article{Senseman:2002, Abstract = {In the pond turtle, Pseudemys scripta elegans, visually evoked cortical waves propagate at different velocities within the primary visual area compared with waves that pass into the secondary visual area. In an effort to separate intra- and intercortical wave motions, movies of visually evoked cortical waves recorded by high-speed voltage-sensitive dye (VSD) imaging were subjected to Karhunen-Lo{\'e}ve (KL) decomposition. This procedure decomposes the VSD movies into a series of basis images that capture different spatial patterns of coherent activity. Most of the energy of the compound wave motion (>95%) was captured by the three largest basis images, M(1,1), M(1,2), and M(2,1). Based on visual comparison with maps of wave front latency, KL basis image M(1,2) appears to capture the spread of depolarization within the primary visual area, whereas KL basis image M(2,1) appears to capture the spread of depolarization from the primary into the secondary visual area. The contribution of different basis images to the intra- and intercortical wave motions was tested by reconstructing the response using different combinations of KL basis images. Only KL basis images M(1,1) and M(1,2) were needed to reconstruct intracortical wave motion, while basis images M(1,1) and M(2,1) were needed to reconstruct intercortical wave motion. It was also found that the direction and speed of wave propagation could be deduced by visual inspection of the basis image projections on to the original data set. The relative advantage of KL decomposition for the analysis of complex wave motions captured by VSD imaging is discussed.}, Author = {Senseman, David M and Robbins, Kay A}, Date-Added = {2013-06-12 18:10:55 +0000}, Date-Modified = {2013-06-12 18:17:17 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {computation biology; models; Computer Simulation; neurophysiology; optical imaging; voltage sensor; Visual Cortex; visual system; next}, Mesh = {Animals; Coloring Agents; Evoked Potentials, Visual; Image Processing, Computer-Assisted; Membrane Potentials; Models, Neurological; Photic Stimulation; Reaction Time; Turtles; Visual Cortex}, Month = {Mar}, Number = {3}, Pages = {1499-514}, pmid = {11877522}, Pst = {ppublish}, Title = {High-speed VSD imaging of visually evoked cortical waves: decomposition into intra- and intercortical wave motions}, Volume = {87}, Year = {2002}, url = {papers/Senseman_JNeurophysiol2002.pdf}} @article{Robbins:2004, Abstract = {Waves have long been thought to be a fundamental mechanism for communicating information within a medium and are widely observed in biological systems. However, a quantitative analysis of biological waves is confounded by the variability and complexity of the response. This paper proposes a robust technique for extracting wave structure from experimental data by calculating "wave subspaces" from the KL decomposition of the data set. If a wave subspace contains a substantial portion of the data set energy during a particular time interval, one can deduce the structure of the wave and potentially isolate its information content. This paper uses the wave subspace technique to extract and compare wave structure in data from three different preparations of the turtle visual cortex. The paper demonstrates that wave subspace caricatures from the three cortical preparations have qualitative similarities. In the numerical model, where information about the underlying dynamics is available, wave subspace landmarks are related to activation and changes in behavior of other dynamic variables besides membrane potential.}, Author = {Robbins, Kay A and Senseman, David M}, Date = {2004 May-Jun}, Date-Added = {2013-06-12 18:09:28 +0000}, Date-Modified = {2013-06-12 18:10:31 +0000}, Doi = {10.1023/B:JCNS.0000025689.01581.26}, Journal = {J Comput Neurosci}, Journal-Full = {Journal of computational neuroscience}, Keywords = {computation biology; models; Computer Simulation; Mathematics; Visual Cortex; Turtles; visual system; wave}, Mesh = {Animals; Computer Simulation; Dose-Response Relationship, Radiation; Evoked Potentials, Visual; Geniculate Bodies; Membrane Potentials; Models, Neurological; Neurons; Photic Stimulation; Principal Component Analysis; Reaction Time; Receptors, AMPA; Receptors, GABA; Receptors, N-Methyl-D-Aspartate; Space Perception; Time Factors; Turtles; Visual Cortex; Visual Pathways}, Number = {3}, Pages = {267-98}, pmid = {15114050}, Pst = {ppublish}, Title = {Extracting wave structure from biological data with application to responses in turtle visual cortex}, Volume = {16}, Year = {2004}, url = {papers/Robbins_JComputNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1023/B:JCNS.0000025689.01581.26}} @article{Nenadic:2003, Abstract = {This article describes a large-scale model of turtle visual cortex that simulates the propagating waves of activity seen in real turtle cortex. The cortex model contains 744 multicompartment models of pyramidal cells, stellate cells, and horizontal cells. Input is provided by an array of 201 geniculate neurons modeled as single compartments with spike-generating mechanisms and axons modeled as delay lines. Diffuse retinal flashes or presentation of spots of light to the retina are simulated by activating groups of geniculate neurons. The model is limited in that it does not have a retina to provide realistic input to the geniculate, and the cortex and does not incorporate all of the biophysical details of real cortical neurons. However, the model does reproduce the fundamental features of planar propagating waves. Activation of geniculate neurons produces a wave of activity that originates at the rostrolateral pole of the cortex at the point where a high density of geniculate afferents enter the cortex. Waves propagate across the cortex with velocities of 4 microm/ms to 70 microm/ms and occasionally reflect from the caudolateral border of the cortex.}, Author = {Nenadic, Zoran and Ghosh, Bijoy K and Ulinski, Philip}, Date = {2003 Mar-Apr}, Date-Added = {2013-06-12 17:53:07 +0000}, Date-Modified = {2013-06-12 18:05:54 +0000}, Journal = {J Comput Neurosci}, Journal-Full = {Journal of computational neuroscience}, Keywords = {computation biology; Computer Simulation; models; Turtles; neurophysiology; waves; Visual Cortex; visual system; Mathematics; technique; next}, Mesh = {Algorithms; Animals; Axons; Computer Simulation; Demography; Dendrites; Excitatory Postsynaptic Potentials; Geniculate Bodies; Membrane Potentials; Models, Neurological; Neurons; Photic Stimulation; Pyramidal Cells; Reaction Time; Receptors, AMPA; Receptors, GABA-A; Receptors, GABA-B; Receptors, N-Methyl-D-Aspartate; Synapses; Time Factors; Turtles; Visual Cortex; Visual Pathways}, Number = {2}, Pages = {161-84}, pmid = {12567015}, Pst = {ppublish}, Title = {Propagating waves in visual cortex: a large-scale model of turtle visual cortex}, Volume = {14}, Year = {2003}, url = {papers/Nenadic_JComputNeurosci2003.pdf}, Bdsk-File-2 = {papers/Nenadic_JComputNeurosci2003a.pdf}} @article{Godecke:1996, Abstract = {In the mammalian visual cortex, many neurons are driven binocularly and response properties such as orientation preference or spatial frequency tuning are virtually identical for the two eyes. A precise match of orientation is essential in order to detect disparity and is therefore a prerequisite for stereoscopic vision. It is not clear whether this match is accomplished by activity-dependent mechanisms together with the common visual experience normally received by the eyes, or whether the visual system relies on other, perhaps even innate, cues to achieve this task. Here we test whether visual experience is responsible for the match in a reverse-suturing experiment in which kittens were raised so that both eyes were never able to see at the same time. A comparison of the layout of the two maps formed under these conditions showed them to be virtually identical. Considering that the two eyes never had common visual experience, this indicates that correlated visual input is not required for the alignment of orientation preference maps.}, Author = {G{\"o}decke, I and Bonhoeffer, T}, Date-Added = {2013-06-10 19:48:54 +0000}, Date-Modified = {2013-06-10 19:50:54 +0000}, Doi = {10.1038/379251a0}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {cat; kitten; spontaneous activity; activity manipulation; activity-development; development; Visual Cortex; Neocortex; visual system; topographic map}, Mesh = {Animals; Brain Mapping; Cats; Ocular Physiological Phenomena; Ophthalmologic Surgical Procedures; Orientation; Sensory Deprivation; Sutures; Vision, Binocular; Vision, Ocular; Visual Cortex}, Month = {Jan}, Number = {6562}, Pages = {251-4}, pmid = {8538789}, Pst = {ppublish}, Title = {Development of identical orientation maps for two eyes without common visual experience}, Volume = {379}, Year = {1996}, url = {papers/Gödecke_Nature1996.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/379251a0}} @article{Toth:1989, Abstract = {In juvenile and adult Xenopus laevis, in adult Bufo marinus and Rana esculenta frogs retino-retinal projections were traced by filling the central stump of one optic nerve, cut 2-3 mm from the eye, with horse-radish peroxidase (HRP) or cobaltic-lysine complex (CLC). The presence of retino-retinal projections was confirmed in all 3 species both in the juvenile and the adult. Up to 12 ganglion cells per retina were found to be filled retrogradely with HRP together with optic axons filled anterogradely with CLC. These findings suggest that (1) a small proportion of ganglion cells project, erroneously, to the opposite retina and (2) this erroneous retino-retinal projection persists throughout the whole lifespan of the animals.}, Author = {T{\'o}th, P and Straznicky, C}, Date-Added = {2013-06-10 18:42:13 +0000}, Date-Modified = {2013-06-10 19:17:29 +0000}, Journal = {Neurosci Lett}, Journal-Full = {Neuroscience letters}, Keywords = {retino-retinal; retino-retino; retinopetal; mirror symmetry; development; activity-development; frog; Amphibia; growth; retina; visual system; tracer; anatomy; connectivity}, Mesh = {Animals; Axons; Bufo marinus; Cobalt; Horseradish Peroxidase; Lysine; Neural Pathways; Optic Nerve; Rana esculenta; Retina; Retinal Ganglion Cells; Xenopus laevis}, Month = {Sep}, Number = {1-2}, Pages = {43-7}, pmid = {2510094}, Pst = {ppublish}, Title = {Retino-retinal projections in three anuran species}, Volume = {104}, Year = {1989}, url = {papers/Tóth_NeurosciLett1989.pdf}} @article{Sarnaik:2013, Abstract = {The convergence of eye-specific thalamic inputs to visual cortical neurons forms the basis of binocular vision. Inputs from the same eye that signal light increment (On) and decrement (Off) are spatially segregated into subregions, giving rise to cortical receptive fields (RFs) that are selective for stimulus orientation. Here we map RFs of binocular neurons in the mouse primary visual cortex using spike-triggered average. We find that subregions of the same sign (On-On and Off-Off) preferentially overlap between the 2 monocular RFs, leading to binocularly matched orientation tuning. We further demonstrate that such subregion correspondence and the consequent matching of RF orientation are disrupted in mice reared in darkness during development. Surprisingly, despite the lack of all postnatal visual experience, a substantial degree of subregion correspondence still remains. In addition, dark-reared mice show normal monocular RF structures and binocular overlap. These results thus reveal the specific roles of experience-dependent and -independent processes in binocular convergence and refinement of On and Off inputs onto single cortical neurons.}, Author = {Sarnaik, Rashmi and Wang, Bor-Shuen and Cang, Jianhua}, Date-Added = {2013-06-10 17:03:05 +0000}, Date-Modified = {2013-08-28 14:53:55 +0000}, Doi = {10.1093/cercor/bht027}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {spontaneous activity; topographic map; mouse; neurophysiology; activity-development; currOpinRvw; Orientation; Visual Cortex; visual system; currOpinRvw}, Month = {Feb}, pmid = {23389996}, Pst = {aheadofprint}, Title = {Experience-Dependent and Independent Binocular Correspondence of Receptive Field Subregions in Mouse Visual Cortex}, Year = {2013}, url = {papers/Sarnaik_CerebCortex2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bht027}} @article{Huberman:2005, Abstract = {Axon guidance cues contributing to the development of eye-specific visual projections to the lateral geniculate nucleus (LGN) have not previously been identified. Here we show that gradients of ephrin-As and their receptors (EphAs) direct retinal ganglion cell (RGC) axons from the two eyes into their stereotyped pattern of layers in the LGN. Overexpression of EphAs in ferret RGCs using in vivo electroporation induced axons from both eyes to misproject within the LGN. The effects of EphA overexpression were competition-dependent and restricted to the early postnatal period. These findings represent the first demonstration of eye-specific pathfinding mediated by axon guidance cues and, taken with other reports, indicate that ephrin-As can mediate several mapping functions within individual target structures.}, Author = {Huberman, Andrew D and Murray, Karl D and Warland, David K and Feldheim, David A and Chapman, Barbara}, Date-Added = {2013-06-10 16:30:29 +0000}, Date-Modified = {2013-06-10 16:36:56 +0000}, Doi = {10.1038/nn1505}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {ferret; Anatomy; topographic map; Genes; development; activity-development; Spontaneous activity}, Mesh = {Aging; Animals; Animals, Newborn; Axons; Electroporation; Ephrin-A3; Ephrin-A5; Female; Ferrets; Geniculate Bodies; Green Fluorescent Proteins; Luminescent Agents; Male; Receptor, EphA3; Receptor, EphA5; Receptors, Eph Family; Retinal Ganglion Cells; Synaptic Transmission; Visual Pathways}, Month = {Aug}, Number = {8}, Pages = {1013-21}, Pmc = {PMC2652399}, pmid = {16025110}, Pst = {ppublish}, Title = {Ephrin-As mediate targeting of eye-specific projections to the lateral geniculate nucleus}, Volume = {8}, Year = {2005}, url = {papers/Huberman_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1505}} @article{Cang:2013, Abstract = {Brain connections are organized into topographic maps that are precisely aligned both within and across modalities. This alignment facilitates coherent integration of different categories of sensory inputs and allows for proper sensorimotor transformations. Topographic maps are established and aligned by multistep processes during development, including interactions of molecular guidance cues expressed in gradients; spontaneous activity-dependent axonal and dendritic remodeling; and sensory-evoked plasticity driven by experience. By focusing on the superior colliculus, a major site of topographic map alignment for different sensory modalities, this review summarizes current understanding of topographic map development in the mammalian visual system and highlights recent advances in map alignment studies. A major goal looking forward is to reveal the molecular and synaptic mechanisms underlying map alignment and to understand the physiological and behavioral consequences when these mechanisms are disrupted at various scales. Expected final online publication date for the Annual Review of Neuroscience Volume 36 is July 08, 2013. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.}, Author = {Cang, Jianhua and Feldheim, David A}, Date-Added = {2013-06-10 13:05:55 +0000}, Date-Modified = {2013-08-27 02:57:51 +0000}, Doi = {10.1146/annurev-neuro-062012-170341}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {currOpinRvw; spontaneous activity; visual system; retina; superior colliculus; review literature; Visual Cortex; topographic map; activity-development; activity manipulation; Genes; trophic signal; currOpinRvw}, Month = {Apr}, pmid = {23642132}, Pst = {aheadofprint}, Title = {Developmental Mechanisms of Topographic Map Formation and Alignment}, Year = {2013}, url = {papers/Cang_AnnuRevNeurosci2013.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev-neuro-062012-170341}} @article{Friauf:1991, Abstract = {1. The development of excitatory activation in the visual cortex was studied in fetal and neonatal cats. During fetal and neonatal life, the immature cerebral cortex (the cortical plate) is sandwiched between two synaptic zones: the marginal zone above, and an area just below the cortical plate, the subplate. The subplate is transient and disappears by approximately 2 mo postnatal. Here we have investigated whether the subplate and the cortical plate receive functional synaptic inputs in the fetus, and when the adultlike pattern of excitatory synaptic input to the cortical plate appears during development. 2. Extracellular field potential recording to electrical stimulation of the optic radiation was performed in slices of cerebral cortex maintained in vitro. Laminar profiles of field potentials were converted by the current-source density (CSD) method to identify the spatial and temporal distribution of neuronal excitation within the subplate and the cortical plate. 3. Between embryonic day 47 (E47) and postnatal day 28 (P28; birth, E65), age-related changes occur in the pattern of synaptic activation of neurons in the cortical plate and the subplate. Early in development, at E47, E57, and P0, short-latency (probably monosynaptic) excitation is most obvious in the subplate, and longer latency (presumably polysynaptic) excitation can be seen in the cortical plate. Synaptic excitation in the subplate is no longer apparent at P21 and P28, a time when cell migration is finally complete and the cortical layers have formed. By contrast, excitation in the cortical plate is prominent in postnatal animals, and the temporal and spatial pattern has changed. 4. The adultlike sequence of synaptic activation in the different cortical layers can be seen by P28. It differs from earlier ages in several respects. First, short-latency (probably monosynaptic) excitation can be detected in cortical layer 4. Second, multisynaptic, long-lasting activation is present in layers 2/3 and 5. 5. Our results show that the subplate zone, known from anatomic studies to be a synaptic neurophil during development, receives functional excitatory inputs from axons that course in the developing white matter. Because the only mature neurons present in this zone are the subplate neurons, we conclude that subplate neurons are the principal, if not the exclusive, recipients of this input. The results suggest further that the excitation in the subplate in turn is relayed to neurons of the cortical plate via axon collaterals of subplate neurons.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Friauf, E and Shatz, C J}, Date-Added = {2013-05-31 19:22:12 +0000}, Date-Modified = {2013-08-27 03:06:44 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {neurophysiology; extracellular; electrical recording; development; synapses; Stimulation; in vitro; cat; kitten; Visual Cortex; neocortex;; currOpinRvw}, Mesh = {Aging; Animals; Animals, Newborn; Electric Stimulation; Fetus; Gestational Age; Membrane Potentials; Neurons; Synapses; Visual Cortex}, Month = {Dec}, Number = {6}, Pages = {2059-71}, pmid = {1812236}, Pst = {ppublish}, Title = {Changing patterns of synaptic input to subplate and cortical plate during development of visual cortex}, Volume = {66}, Year = {1991}, url = {papers/Friauf_JNeurophysiol1991.pdf}} @article{McConnell:1989, Abstract = {During the development of the nervous system, growing axons must traverse considerable distances to find their targets. In insects, this problem is solved in part by pioneer neurons, which lay down the first axonal pathways when distances are at a minimum. Here the existence of a similar kind of neuron in the developing mammalian telencephalon is described. These are the subplate cells, the first postmitotic neurons of the cerebral cortex. Axons from subplate neurons traverse the internal capsule and invade the thalamus early in fetal life, even before the neurons of cortical layers 5 and 6, which will form the adult subcortical projections, are generated. During postnatal life, after the adult pattern of axonal projections is firmly established, most subplate neurons disappear. These observations raise the possibility that the early axonal scaffold formed by subplate cells may prove essential for the establishment of permanent subcortical projections.}, Author = {McConnell, S K and Ghosh, A and Shatz, C J}, Date-Added = {2013-05-31 17:38:19 +0000}, Date-Modified = {2013-05-31 17:38:25 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {development; subplate neurons; cat; neocortex; cerebral cortex; patterning; topographic map; axon guidance; visual cortex; activity-development}, Mesh = {Animals; Axonal Transport; Axons; Cats; Cerebral Cortex; Embryonic and Fetal Development; Fluorescent Dyes; Neurons; Superior Colliculi; Thalamus}, Month = {Sep}, Number = {4921}, Pages = {978-82}, pmid = {2475909}, Pst = {ppublish}, Title = {Subplate neurons pioneer the first axon pathway from the cerebral cortex}, Volume = {245}, Year = {1989}, url = {papers/McConnell_Science1989.pdf}} @article{Ghosh:1992a, Abstract = {During development of the mammalian cerebral cortex, thalamic axons must grow into the telencephalon and select appropriate cortical targets. In order to begin to understand the cellular interactions that are important in cortical target selection by thalamic axons, we have examined the morphology of axons from the lateral geniculate nucleus (LGN) as they navigate their way to the primary visual cortex. The morphology of geniculocortical axons was revealed by placing the lipophilic tracer Dil into the LGN of paraformaldehyde-fixed brains from fetal and neonatal cats between embryonic day 26 (E26; gestation is 65 d) and postnatal day 7 (P7). This morphological approach has led to three major observations. (1) As LGN axons grow within the intermediate zone of the telencephalon toward future visual cortex (E30-40), many give off distinct interstitial axon collaterals that penetrate the subplate of nonvisual cortical areas. These collaterals are transient and are not seen postnatally. (2) There is a prolonged period during which LGN axons are restricted to the visual subplate prior to their ingrowth into the cortical plate; the first LGN axons arrive within visual subplate by E36 but are not detected in layer 6 of visual cortex until about E50. (3) Within the visual subplate, LGN axons extend widespread terminal branches. This represents a marked change in their morphology from the simple growth cones present earlier as LGN axons navigate en route to visual cortex. The presence of interstitial collaterals suggests that there may be ongoing interactions between LGN axons and subplate neurons along the entire intracortical route traversed by the axons. From the extensive branching of LGN axons within the visual subplate during the waiting period, it appears that they are not simply "waiting." Rather, LGN axons may participate in dynamic cellular interactions within the subplate long before they contact their ultimate target neurons in layer 4. These observations confirm the existence of a prolonged waiting period in the development of thalamocortical connections and provide important morphological evidence in support of the previous suggestion that interactions between thalamic axons and subplate neurons are necessary for cortical target selection.}, Author = {Ghosh, A and Shatz, C J}, Date-Added = {2013-05-31 17:28:45 +0000}, Date-Modified = {2013-05-31 17:34:43 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; subplate neurons; cat; neocortex; cerebral cortex; patterning; topographic map; axon guidance; visual cortex; activity-development}, Mesh = {Aging; Animals; Animals, Newborn; Axons; Carbocyanines; Cats; Fluorescent Dyes; Geniculate Bodies; Gestational Age; Neural Pathways; Telencephalon; Thalamus; Visual Cortex}, Month = {Jan}, Number = {1}, Pages = {39-55}, pmid = {1729444}, Pst = {ppublish}, Title = {Pathfinding and target selection by developing geniculocortical axons}, Volume = {12}, Year = {1992}} @article{Ghosh:1994, Abstract = {To investigate the cellular interactions within the mammalian visual cortex that are important in ocular dominance column formation, we have examined the role of subplate neurons in this process. LGN axons segregate in layer 4 of the cat's visual cortex between the third and sixth postnatal weeks to give rise to the adult pattern of ocular dominance columns. Subplate neurons are a transient population of neurons that sit in the white matter but have extensive projections into the overlying cortex, particularly layer 4, during neonatal life. Many subplate neurons are present at birth, but most are gone by the end of the period of LGN axon segregation. To examine whether these neurons are required for the segregation of LGN axons, we deleted them by intracortical injections of kainic acid either just after LGN axons had grown into layer 4 (first postnatal week) or later, just before the onset of segregation (third postnatal week). The consequences for the patterning of geniculocortical terminals were evaluated by transneuronal transport of 3H-proline injected into one eye at times when segregation would normally be complete. Following deletion of subplate neurons at either age, LGN axons failed to segregate into ocular dominance columns. Following the late deletions only, geniculocortical axons lost their laminar restriction to layer 4 and projected to layers 2 and 3 as well. Deletion of subplate neurons also resulted in long-term changes in the cytoarchitecture of layer 4. These observations suggest that the interactions that mediate segregation of LGN axons within layer 4 of visual cortex are susceptible to influences from subplate neurons. Although the mechanisms by which subplate neurons exert their effect are not yet clear, these experiments strongly suggest that interactions between LGN axons and layer 4 neurons are not sufficient for column formation, and that subplate neurons most likely play a critical role in interactions leading to ocular segregation.}, Author = {Ghosh, A and Shatz, C J}, Date-Added = {2013-05-31 17:28:34 +0000}, Date-Modified = {2013-05-31 17:34:43 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; subplate neurons; cat; neocortex; cerebral cortex; patterning; topographic map; axon guidance; visual cortex; activity-development}, Mesh = {Aging; Animals; Animals, Newborn; Axons; Cats; Cerebral Cortex; Functional Laterality; Geniculate Bodies; Kainic Acid; Neurons; Neurons, Afferent; Ocular Physiological Phenomena; Time Factors; Visual Cortex}, Month = {Jun}, Number = {6}, Pages = {3862-80}, pmid = {8207493}, Pst = {ppublish}, Title = {Segregation of geniculocortical afferents during the critical period: a role for subplate neurons}, Volume = {14}, Year = {1994}} @article{McConnell:1994, Abstract = {The adult cerebral cortex extends axons to a variety of subcortical targets, including the thalamus and superior colliculus. These descending projections are pioneered during development by the axons of a transient population of subplate neurons (McConnell et al., 1989). We show here that the descending axons of cortical plate neurons appear to be delayed significantly in their outgrowth, compared with those of subplate neurons. To assess the possible role of subplate neurons in the formation of these pathways, subplate neurons were ablated during the embryonic period. In all cases, an axon pathway formed from visual cortex through the internal capsule and into the thalamus. In half of all cases, however, cortical axons failed to invade their normal subcortical targets. In the other half, targets were innervated normally. Subplate neurons are therefore likely to provide important cues that aid the process by which cortical axons grow toward, select, and invade their subcortical targets.}, Author = {McConnell, S K and Ghosh, A and Shatz, C J}, Date-Added = {2013-05-31 17:28:27 +0000}, Date-Modified = {2013-05-31 17:34:43 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; subplate neurons; cat; neocortex; cerebral cortex; patterning; topographic map; axon guidance; visual cortex; activity-development}, Mesh = {Afferent Pathways; Animals; Animals, Newborn; Axonal Transport; Axons; Carbocyanines; Cats; Cerebral Cortex; Efferent Pathways; Fetus; Fluorescent Dyes; Models, Neurological; Neurons; Temporal Lobe; Thalamus; Visual Cortex}, Month = {Apr}, Number = {4}, Pages = {1892-907}, pmid = {7512631}, Pst = {ppublish}, Title = {Subplate pioneers and the formation of descending connections from cerebral cortex}, Volume = {14}, Year = {1994}} @article{Ghosh:1992, Abstract = {During development of the mammalian visual system, axon terminals of lateral geniculate nucleus (LGN) neurons, initially intermixed within layer 4 of the visual cortex, gradually segregate according to eye preference to form ocular dominance columns. In addition to LGN axons and layer 4 neurons, subplate neurons may also participate in interactions leading to column formation. Deletion of subplate neurons before the formation of ocular dominance columns prevents the segregation of LGN axons within layer 4. Thus, interactions between LGN axons and layer 4 neurons are not sufficient; subplate neurons are also required for formation of ocular dominance columns in the visual cortex.}, Author = {Ghosh, A and Shatz, C J}, Date-Added = {2013-05-31 17:28:05 +0000}, Date-Modified = {2013-05-31 17:34:43 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {development; subplate neurons; cat; neocortex; cerebral cortex; patterning; topographic map; axon guidance; visual cortex; activity-development}, Mesh = {Animals; Animals, Newborn; Axons; Cats; Cell Death; Kainic Acid; Neurons; Ocular Physiological Phenomena; Visual Cortex; Visual Pathways}, Month = {Mar}, Number = {5050}, Pages = {1441-3}, pmid = {1542795}, Pst = {ppublish}, Title = {Involvement of subplate neurons in the formation of ocular dominance columns}, Volume = {255}, Year = {1992}, url = {papers/Ghosh_Science1992.pdf}} @article{Ghosh:1990, Abstract = {The neurons of layer 4 in the adult cerebral cortex receive their major ascending inputs from the thalamus. In development, however, thalamic axons arrive at the appropriate cortical area long before their target layer 4 neurons have migrated into the cortical plate. The axons accumulate and wait in the zone below the cortical plate, the subplate, for several weeks before invading the cortical plate. The subplate is a transient zone that contains the first postmitotic neurons of the telencephalon. These neurons mature well before other cortical neurons, and disappear by cell death after the thalamic axons have grown into the overlying cortical plate. The close proximity of growing thalamocortical axons and subplate neurons suggests that they might be involved in interactions important for normal thalamocortical development. Here we show that early in development the deletion of subplate neurons located beneath visual cortex prevents axons from the lateral geniculate nucleus of the thalamus from recognizing and innervating visual cortex, their normal target. In the absence of subplate neurons, lateral geniculate nucleus axons continue to grow in the white matter past visual cortex despite the presence of their target layer 4 neurons. Thus the transient subplate neurons are necessary for appropriate cortical target selection by thalamocortical axons.}, Author = {Ghosh, A and Antonini, A and McConnell, S K and Shatz, C J}, Date-Added = {2013-05-31 17:28:01 +0000}, Date-Modified = {2013-05-31 17:34:43 +0000}, Doi = {10.1038/347179a0}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {development; subplate neurons; cat; neocortex; cerebral cortex; patterning; topographic map; axon guidance; visual cortex; activity-development}, Mesh = {Animals; Axons; Cats; Cell Movement; Cell Survival; Cerebral Cortex; Immunohistochemistry; Kainic Acid; Microtubule-Associated Proteins; Neurons; Thalamus; Visual Cortex}, Month = {Sep}, Number = {6289}, Pages = {179-81}, pmid = {2395469}, Pst = {ppublish}, Title = {Requirement for subplate neurons in the formation of thalamocortical connections}, Volume = {347}, Year = {1990}, url = {papers/Ghosh_Nature1990.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/347179a0}} @article{Demas:2012, Abstract = {Developing amphibians need vision to avoid predators and locate food before visual system circuits fully mature. Xenopus tadpoles can respond to visual stimuli as soon as retinal ganglion cells (RGCs) innervate the brain, however, in mammals, chicks and turtles, RGCs reach their central targets many days, or even weeks, before their retinas are capable of vision. In the absence of vision, activity-dependent refinement in these amniote species is mediated by waves of spontaneous activity that periodically spread across the retina, correlating the firing of action potentials in neighboring RGCs. Theory suggests that retinorecipient neurons in the brain use patterned RGC activity to sharpen the retinotopy first established by genetic cues. We find that in both wild type and albino Xenopus tadpoles, RGCs are spontaneously active at all stages of tadpole development studied, but their population activity never coalesces into waves. Even at the earliest stages recorded, visual stimulation dominates over spontaneous activity and can generate patterns of RGC activity similar to the locally correlated spontaneous activity observed in amniotes. In addition, we show that blocking AMPA and NMDA type glutamate receptors significantly decreases spontaneous activity in young Xenopus retina, but that blocking GABA(A) receptor blockers does not. Our findings indicate that vision drives correlated activity required for topographic map formation. They further suggest that developing retinal circuits in the two major subdivisions of tetrapods, amphibians and amniotes, evolved different strategies to supply appropriately patterned RGC activity to drive visual circuit refinement.}, Author = {Demas, James A and Payne, Hannah and Cline, Hollis T}, Date-Added = {2013-05-31 16:22:46 +0000}, Date-Modified = {2013-05-31 16:33:28 +0000}, Doi = {10.1002/dneu.20880}, Journal = {Dev Neurobiol}, Journal-Full = {Developmental neurobiology}, Keywords = {retinal waves; spontaneous activity; Xenopus; vision; Activity-development; development; topographic map; visual system; retina; Retinal Ganglion Cells; currOpinRvw}, Mesh = {Animals; Electrophysiology; Neurogenesis; Retina; Retinal Ganglion Cells; Vision, Ocular; Visual Pathways; Xenopus}, Month = {Apr}, Number = {4}, Pages = {537-46}, Pmc = {PMC3157589}, pmid = {21312343}, Pst = {ppublish}, Title = {Vision drives correlated activity without patterned spontaneous activity in developing Xenopus retina}, Volume = {72}, Year = {2012}, url = {papers/Demas_DevNeurobiol2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dneu.20880}} @article{Grzywacz:2000, Abstract = {We report on the temporal properties of the spontaneous bursts of activity in the developing turtle retina. Quantitative statistical criteria were used to detect, cluster, and analyze the temporal properties of the bursts. The interburst interval, duration, firing rate, and number of spikes per burst varied widely among cells and from burst to burst in a single cell. Part of this variability was due to the positive correlation between a burst's duration and the interburst interval preceding that burst. This correlation indicated the influence of a refractory period on the bursts' properties. Further evidence of such a refractoriness came from the bursts' auto-covariance function, which gives the tendency of a spike to occur a given amount of time after another spike. This function showed a positive phase (between approximately 10 ms and 10 s) followed by a negative one (between 10 s and more than 100 s), suggestive of burst refractoriness. The bursts seemed to be propagating from cell to cell, because there was a long (symmetrically distributed) delay between the activation of two neighbor cells (median absolute delay = 2.3 s). However, the activity often failed to propagate from one cell to the other (median safety factor = 0.59). The number of spikes per burst in neighbor cells was statistically positively correlated, indicating that the activity in the two cells was driven by the same excitatory process. At least two factors contribute to the excitability during bursts, because the positive phase of the cross-covariance function (similar to auto-covariance but for two cells) had a temporally asymmetric fast component (1-3 ms) followed by a temporally symmetric slow component (1 ms to 10 s).}, Author = {Grzywacz, N M and Sernagor, E}, Date = {2000 Mar-Apr}, Date-Added = {2013-05-31 16:04:51 +0000}, Date-Modified = {2013-05-31 16:05:54 +0000}, Journal = {Vis Neurosci}, Journal-Full = {Visual neuroscience}, Keywords = {retinal waves; turtle; Retina; visual system; spontaneous activity; development}, Mesh = {Animals; Cluster Analysis; Electrophysiology; Microelectrodes; Retinal Ganglion Cells; Turtles}, Number = {2}, Pages = {229-41}, pmid = {10824677}, Pst = {ppublish}, Title = {Spontaneous activity in developing turtle retinal ganglion cells: statistical analysis}, Volume = {17}, Year = {2000}} @article{Sernagor:1999, Abstract = {Extracellular recordings were obtained from the ganglion cell (GC) layer during correlated spontaneous bursting activity (SBA) in the immature turtle retina. Pharmacological agents were bath-applied, and their effects on burst and correlation parameters were determined. SBA requires synaptic transmission. It was blocked in the presence of curare and mecamylamine, two cholinergic nicotinic antagonists, and enhanced with neostigmine, a cholinesterase inhibitor. SBA was profoundly inhibited during blockade of glutamatergic receptors with the broad spectrum antagonist kynurenate and it vanished with 6,7-dinitroquinoxaline-2-3-dione (DNQX) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), two AMPA/kainate receptor antagonists. Blockade of NMDA receptors with D(-)-2-amino-5-phosphonopentanoic acid (D-AP-5) led only to a modest reduction in SBA. Blockade of GABAA receptors with bicuculline prolonged the duration of the bursts. Inhibition of GABA uptake with nipecotic acid led to a decrease in burst rate. Blockade of K+ channels with cesium (Cs+) and tetraethylammonium (TEA) led to a dramatic decrease in excitability. Burst propagation between neighboring GCs was reduced by K+ channel blockade. Gap junction blockade had no consistent effect on bursts or correlation parameters. None of these drugs had a strong effect on the refractory period between bursts. We conclude that correlated SBA in immature turtle GCs requires both cholinergic nicotinic and glutamatergic (mainly through AMPA/kainate receptors) synaptic transmission. GABAergic activity modulates the intensity and the duration of the bursts. Extracellular K+ is involved in lateral activity propagation and increases retinal excitability, which may be required for burst generation.}, Author = {Sernagor, E and Grzywacz, N M}, Date-Added = {2013-05-31 16:04:46 +0000}, Date-Modified = {2013-05-31 16:05:54 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retinal waves; turtle; Retina; visual system; spontaneous activity; development}, Mesh = {Action Potentials; Animals; Embryo, Nonmammalian; Embryonic Development; Excitatory Amino Acid Antagonists; Gap Junctions; Potassium; Retinal Ganglion Cells; Synaptic Transmission; Turtles}, Month = {May}, Number = {10}, Pages = {3874-87}, pmid = {10234019}, Pst = {ppublish}, Title = {Spontaneous activity in developing turtle retinal ganglion cells: pharmacological studies}, Volume = {19}, Year = {1999}, url = {papers/Sernagor_JNeurosci1999.pdf}} @article{Sernagor:1996, Abstract = {BACKGROUND: The role played by early neural activity in shaping retinal functions has not yet been established. In the developing vertebrate retina, ganglion cells fire spontaneous bursts of action potentials before the onset of visual experience. This spontaneous bursting disappears shortly after birth or eye opening. In the present study, we have investigated whether the outgrowth of receptive fields in turtle retinal ganglion cells is affected by early spontaneous bursting or by early visual experience. RESULTS: Ganglion cells normally stop bursting spontaneously 2-4 weeks post-hatching, the time when receptive-field areas reach adult size. When turtles are reared in the dark, the spontaneous bursting persists. Concomitantly, receptive-field areas expand to more than twice those observed in normal adults. To test whether chronic blockade of spontaneous bursting inhibits the expansion of developing receptive-field areas, we have exposed the retina to curare, a nicotinic cholinergic antagonist, because spontaneous bursting by ganglion cells requires acetylcholine. Curare was released from Elvax, a slow-release polymer that was implanted in the eye. When spontaneous bursting was chronically blocked with curare in hatchlings, dark-induced expansion of receptive fields was abolished. Moreover, receptive fields of ganglion cells exposed to curare in hatchlings reared in normal light and dark cycles were smaller than normal. CONCLUSIONS: These results strongly suggest that early, acetylcholine-dependent spontaneous bursts of activity control the outgrowth of receptive-field areas in retinal ganglion cells. The onset of visual experience induces the disappearance of the immature spontaneous bursts, resulting in the stabilization of receptive-field areas to their mature size.}, Author = {Sernagor, E and Grzywacz, N M}, Date-Added = {2013-05-31 16:04:41 +0000}, Date-Modified = {2013-05-31 16:06:12 +0000}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {retinal waves; currOpinRvw; turtle; Retina; visual system; spontaneous activity; development}, Mesh = {Animals; Darkness; Receptors, Cholinergic; Retinal Ganglion Cells; Turtles}, Month = {Nov}, Number = {11}, Pages = {1503-8}, pmid = {8939611}, Pst = {ppublish}, Title = {Influence of spontaneous activity and visual experience on developing retinal receptive fields}, Volume = {6}, Year = {1996}, url = {papers/Sernagor_CurrBiol1996.pdf}} @article{Sernagor:1995, Abstract = {1. Receptive field properties of adult retinal ganglion cells are well documented, but little is known about their development. We made extracellular recordings of activity from turtle retinal ganglion cells during embryogenesis (stages 22-26), during the first 40 days posthatching, and in adults. 2. From stage 22 the cells fired in spontaneous recurring bursts, and from stage 23 they responded to light. Polar plots of the responses to motion were highly anisotropic in early embryonic cells. More than 40% of embryonic cells exhibited multiaxis anisotropy, and only 6% were statistically isotropic. The incidence of anisotropic cells gradually decreased throughout development. The incidence of isotropic cells and the excitatory receptive field diameters of all ganglion cells gradually increased during development and their maturation coincided with the disappearance of the spontaneous bursts (2-4 wk posthatching). 3. Both sensitivities to stimulus orientation and direction of motion were observed at the earliest stages of development. However, orientation selectivity reached a peak incidence at hatching, whereas directional selectivity completely disappeared, only to reappear in adults. 4. These results show that mature spatiotemporal receptive field properties of retinal ganglion cells emerge from initially highly anisotropic properties, which may reflect an immature, polarized dendritic layout. Their maturation might be mediated by dendritic outgrowth and strengthening of excitatory synaptic connections, which could be induced by spontaneous activity and driven to maturation by exposure to light at birth. Mature directional selectivity seems to require visual experience or the late establishment of a specialized inhibitory synaptic drive.}, Author = {Sernagor, E and Grzywacz, N M}, Date-Added = {2013-05-31 16:04:37 +0000}, Date-Modified = {2013-05-31 16:05:54 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {retinal waves; turtle; Retina; visual system; spontaneous activity; development}, Mesh = {Animals; Embryo, Nonmammalian; Extracellular Space; Motion Perception; Orientation; Photic Stimulation; Retina; Retinal Ganglion Cells; Space Perception; Time Perception; Turtles; Visual Fields}, Month = {Apr}, Number = {4}, Pages = {1355-64}, pmid = {7643153}, Pst = {ppublish}, Title = {Emergence of complex receptive field properties of ganglion cells in the developing turtle retina}, Volume = {73}, Year = {1995}, url = {papers/Sernagor_JNeurophysiol1995.pdf}} @article{Wong:1998, Abstract = {Even before birth and the onset of sensory experience, neural activity plays an important role in shaping the vertebrate nervous system. In the embryonic chick visual system, activity in the retina before vision has been implicated in the refinement of retinotopic maps, the elimination of transient projections, and the survival of a full complement of neurons. In this study, we report the detection of a physiological substrate for these phenomena: waves of spontaneous activity in the ganglion cell layer of the embryonic chick retina. The activity is robust and highly patterned, taking the form of large amplitude, rhythmic, and wide-ranging waves of excitation that propagate across the retina. Activity waves are most prominent and organized between embryonic days 13-18, coinciding with the developmental period during which retinal axons refine their connections in their targets. The spatial and temporal features of the patterns observed are consistent with the role of activity patterns in shaping eye-specific projections and retinotopic maps but inconsistent with the hypothesis that they specify lamina-specific projections in the tectum. Antagonists of glutamatergic and glycinergic transmission and of gap junctional communication suppress spontaneous activity, whereas antagonists to GABAergic transmission potentiate it. Based on these results, we propose that spontaneous activity in the ganglion cells is regulated by chemical inputs from both bipolar and amacrine cells and by gap junctional coupling involving ganglion cells.}, Author = {Wong, W T and Sanes, J R and Wong, R O}, Date-Added = {2013-05-31 16:00:35 +0000}, Date-Modified = {2013-05-31 16:00:41 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retinal waves; currOpinRvw; Chick Embryo; Retina; visual system; spontaneous activity}, Mesh = {Animals; Chick Embryo; Cholinergic Antagonists; Electrophysiology; Excitatory Amino Acid Antagonists; Fluorescent Dyes; Fura-2; GABA-A Receptor Antagonists; Gap Junctions; Green Fluorescent Proteins; Indicators and Reagents; Luminescent Proteins; Microscopy, Fluorescence; Receptors, Glycine; Retina; Retinal Ganglion Cells; Synaptic Transmission; Time Factors; Transfection; Visual Cortex}, Month = {Nov}, Number = {21}, Pages = {8839-52}, pmid = {9786990}, Pst = {ppublish}, Title = {Developmentally regulated spontaneous activity in the embryonic chick retina}, Volume = {18}, Year = {1998}, url = {papers/Wong_JNeurosci1998.pdf}} @article{Catsicas:1998, Abstract = {The development of the central nervous system is dependent on spontaneous action potentials and changes in [Ca2+]i occurring in neurons [1-4]. In the mammalian retina, waves of spontaneous electrical activity spread between retinal neurons, raising [Ca2+]i as they pass [5-7]. In the ferret retina, the first spontaneous Ca2+ waves have been reported at postnatal day 2 and are thought to result from the Ca2+ influx associated with bursts of action potentials seen in ganglion cells at this time [5-7]. These waves depend on depolarisation produced by voltage-gated sodium channels, but their initiation and/or propagation also depends upon nicotinic cholinergic synaptic transmission between amacrine cells and ganglion cells [8]. Here, we report contrasting results for the chick retina where Ca2+ transients are seen at times before retinal synapse formation but when there are extensive networks of gap junctions. These Ca2+ transients do not require nicotinic cholinergic transmission but are modulated by acetylcholine (ACh), dopamine and glycine. Furthermore, they propagate into the depth of the retina, suggesting that they are not restricted to ganglion and amacrine cells. The transients are abolished by the gap-junctional blocker octanol. Thus, the Ca2+ transients seen early in chick retinal development are triggered and propagate in the absence of synapses by a mechanism that involves several neurotransmitters and gap junctions.}, Author = {Catsicas, M and Bonness, V and Becker, D and Mobbs, P}, Date-Added = {2013-05-31 15:56:33 +0000}, Date-Modified = {2013-05-31 15:57:08 +0000}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {retinal waves; currOpinRvw; Chick Embryo; Retina; visual system; spontaneous activity}, Mesh = {Acetylcholine; Action Potentials; Animals; Calcium; Chick Embryo; Dopamine; Gap Junctions; Glycine; Neurons; Retina; Tetrodotoxin}, Month = {Feb}, Number = {5}, Pages = {283-6}, pmid = {9501073}, Pst = {ppublish}, Title = {Spontaneous Ca2+ transients and their transmission in the developing chick retina}, Volume = {8}, Year = {1998}, url = {papers/Catsicas_CurrBiol1998.pdf}} @article{Sharma:2010, Abstract = {Regulation of progenitor cell fate determines the numbers of neurons in the developing brain. While proliferation of neural progenitors predominates during early central nervous system (CNS) development, progenitor cell fate shifts toward differentiation as CNS circuits develop, suggesting that signals from developing circuits may regulate proliferation and differentiation. We tested whether activity regulates neurogenesis in vivo in the developing visual system of Xenopus tadpoles. Both cell proliferation and the number of musashi1-immunoreactive progenitors in the optic tectum decrease as visual system connections become stronger. Visual deprivation for 2 days increased proliferation of musashi1-immunoreactive radial glial progenitors, while visual experience increased neuronal differentiation. Morpholino-mediated knockdown and overexpression of musashi1 indicate that musashi1 is necessary and sufficient for neural progenitor proliferation in the CNS. These data demonstrate a mechanism by which increased brain activity in developing circuits decreases cell proliferation and increases neuronal differentiation through the downregulation of musashi1 in response to circuit activity.}, Author = {Sharma, Pranav and Cline, Hollis T}, Date-Added = {2013-05-30 19:52:07 +0000}, Date-Modified = {2013-05-30 19:52:07 +0000}, Doi = {10.1016/j.neuron.2010.09.028}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Adenosine Triphosphatases; Animals; Cell Cycle; Cell Differentiation; Cell Proliferation; Central Nervous System; Immunohistochemistry; Larva; Nerve Tissue Proteins; Neuroglia; Neurons; Photic Stimulation; Ribonucleoproteins; Sensory Deprivation; Stem Cells; Superior Colliculi; Vision, Ocular; Visual Pathways; Xenopus; Xenopus Proteins}, Month = {Nov}, Number = {3}, Pages = {442-55}, Pmc = {PMC3005332}, pmid = {21040846}, Pst = {ppublish}, Title = {Visual activity regulates neural progenitor cells in developing xenopus CNS through musashi1}, Volume = {68}, Year = {2010}, url = {papers/Sharma_Neuron2010.pdf}} @article{Ruthazer:2004, Abstract = {The development of orderly topographic maps in the central nervous system (CNS) results from a collaboration of chemoaffinity cues that establish the coarse organization of the projection and activity-dependent mechanisms that fine-tune the map. Using the retinotectal projection as a model system, we describe evidence that biochemical tags and patterned neural activity work in parallel to produce topographically ordered axonal projections. Finally, we review recent experiments in other CNS projections that support the proposition that cooperation between molecular guidance cues and activity-dependent processes constitutes a general paradigm for CNS map formation.}, Author = {Ruthazer, Edward S and Cline, Hollis T}, Date-Added = {2013-05-30 19:49:36 +0000}, Date-Modified = {2013-05-30 19:49:36 +0000}, Doi = {10.1002/neu.10344}, Journal = {J Neurobiol}, Journal-Full = {Journal of neurobiology}, Mesh = {Animals; Axons; Brain Mapping; Cerebral Cortex; Eye; Models, Neurological; Neurons; Retina; Superior Colliculi; Thalamus; Visual Pathways}, Month = {Apr}, Number = {1}, Pages = {134-46}, pmid = {15007832}, Pst = {ppublish}, Title = {Insights into activity-dependent map formation from the retinotectal system: a middle-of-the-brain perspective}, Volume = {59}, Year = {2004}, url = {papers/Ruthazer_JNeurobiol2004.pdf}} @article{Smetters:1994, Abstract = {Recent studies have shown that electrical activity, particularly that mediated by NMDA receptors, has a profound effect on the development of specific neuronal connections. Blocking NMDA receptors in the ferret's lateral geniculate nucleus prevents the segregation of retinal afferents into ON and OFF sublaminae. We have now examined the involvement of NMDA receptors in the separation of afferents from the two eyes that occurs in the lateral geniculate nucleus several weeks earlier in development. Blockade of NMDA receptor activity does not appear to interfere with this eye-specific segregation.}, Author = {Smetters, D K and Hahm, J and Sur, M}, Date-Added = {2013-05-28 19:49:12 +0000}, Date-Modified = {2013-05-28 19:51:00 +0000}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {Ferrets; LGN; visual system; currOpinRvw}, Mesh = {Animals; Eye; Ferrets; Geniculate Bodies; Neural Pathways; Organ Specificity; Piperazines; Receptors, N-Methyl-D-Aspartate; Retina; Retinal Ganglion Cells}, Month = {Sep}, Number = {1-2}, Pages = {168-78}, pmid = {7834339}, Pst = {ppublish}, Title = {An N-methyl-D-aspartate receptor antagonist does not prevent eye-specific segregation in the ferret retinogeniculate pathway}, Volume = {658}, Year = {1994}} @article{Bickford:2010, Abstract = {The dorsal lateral geniculate nucleus (dLGN) of the mouse has emerged as a model system in the study of thalamic circuit development. However, there is still a lack of information regarding how and when various types of retinal and nonretinal synapses develop. We examined the synaptic organization of the developing mouse dLGN in the common pigmented C57/BL6 strain, by recording the synaptic responses evoked by electrical stimulation of optic tract axons, and by investigating the ultrastructure of identified synapses. At early postnatal ages (P14), when optic tract stimulation routinely evoked an excitatory postsynaptic potential/inhibitory postsynaptic potential (EPSP/IPSP) sequence, with the latter having both a GABA(A) and GABA(B) component. Electrophysiological and ultrastructural observations were consistent. At P7, many synapses were present, but synaptic profiles lacked the ultrastructural features characteristic of the adult dLGN, and little gamma-aminobutyric acid (GABA) could be detected by using immunocytochemical techniques. In contrast, by P14, GABA staining was robust, mature synaptic profiles of retinal and nonretinal origin were easily distinguished, and the size and proportion of synaptic contacts were similar to those of the adult. The emergence of nonretinal synapses coincides with pruning of retinogeniculate connections, and the transition of retinal activity from spontaneous to visually driven. These results indicate that the synaptic architecture of the mouse dLGN is similar to that of other higher mammals, and thus provides further support for its use as a model system for visual system development.}, Author = {Bickford, Martha E and Slusarczyk, Arkadiusz and Dilger, Emily K and Krahe, Thomas E and Kucuk, Can and Guido, William}, Date-Added = {2013-05-28 18:27:19 +0000}, Date-Modified = {2013-05-28 18:28:08 +0000}, Doi = {10.1002/cne.22223}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {Thalamic Nuclei; visual system; LGN; Patch-Clamp Techniques; Voltage-Gated; Calcium Channels; development; synapse formation; plasticity; in vitro; GABA; Mouse}, Mesh = {Animals; Animals, Newborn; Cell Differentiation; Electric Stimulation; Excitatory Postsynaptic Potentials; Geniculate Bodies; Inhibitory Postsynaptic Potentials; Mice; Mice, Inbred C57BL; Microscopy, Immunoelectron; Neural Inhibition; Neuronal Plasticity; Organ Culture Techniques; Photic Stimulation; Presynaptic Terminals; Receptors, GABA-A; Receptors, GABA-B; Retinal Ganglion Cells; Synapses; Visual Pathways; gamma-Aminobutyric Acid}, Month = {Mar}, Number = {5}, Pages = {622-35}, pmid = {20034053}, Pst = {ppublish}, Title = {Synaptic development of the mouse dorsal lateral geniculate nucleus}, Volume = {518}, Year = {2010}, url = {papers/Bickford_JCompNeurol2010.pdf}} @article{Guido:2008, Abstract = {Much of our present understanding about the mechanisms contributing to the activity-dependent refinement of sensory connections comes from experiments done in the retinogeniculate pathway. In recent years the mouse has emerged as a model system of study. This review outlines the major changes in connectivity that occur in this species and a potential mechanism that can account for such remodelling. During early postnatal life when spontaneous activity of retinal ganglion cells sweeps across the retina in waves, retinal projections from the two eyes to the dorsal lateral geniculate nucleus (LGN) segregate to form non-overlapping eye-specific domains. There is a loss of binocular innervation, a pruning of excitatory inputs from a dozen or more to one or two, and the emergence of inhibitory circuitry. Many of these changes underlie the development of precise eye-specific visual maps and receptive field structure of LGN neurons. Retinal activity plays a major role both in the induction and maintenance of this refinement. The activity-dependent influx of Ca(2+) through L-type channels and associated activation of CREB signalling may underlie the pruning and stabilization of developing retinogeniculate connections.}, Author = {Guido, William}, Date-Added = {2013-05-28 18:26:31 +0000}, Date-Modified = {2013-05-28 18:27:09 +0000}, Doi = {10.1113/jphysiol.2008.157115}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {Thalamic Nuclei; visual system; LGN; Patch-Clamp Techniques; Voltage-Gated; Calcium Channels; development; synapse formation; plasticity; in vitro; review literature}, Mesh = {Afferent Pathways; Animals; Animals, Newborn; Calcium Channels, L-Type; Geniculate Bodies; Retina; Synapses}, Month = {Sep}, Number = {Pt 18}, Pages = {4357-62}, Pmc = {PMC2614014}, pmid = {18556365}, Pst = {ppublish}, Title = {Refinement of the retinogeniculate pathway}, Volume = {586}, Year = {2008}, url = {papers/Guido_JPhysiol2008.pdf}} @article{Ziburkus:2009, Abstract = {The purpose of the present study was to determine whether retinal activity can support long-term changes in synaptic strength in the developing dorsal lateral geniculate nucleus (LGN) of thalamus. To test for this we made use of a rodent in vitro explant preparation in which retinal afferents and the intrinsic circuitry of the LGN remain intact. We repetitively stimulated the optic tract with a tetanus protocol that approximated the temporal features of spontaneous retinal waves. We found the amplitude of extracellular field potentials evoked by retinal stimulation changed significantly after tetanus and that the polarity of these alterations was related to postnatal age. At a time when substantial pruning of retinal connections occurs (postnatal day 1 [P1] to P14), high-frequency stimulation led to an immediate and long-term depression (LTD). However, at times when pruning wanes and adult-like patterns of connectivity are stabilizing (P16 to P30), the identical form of stimulation produced a modest form of potentiation (long-term potentiation [LTP]). The LTD was unaffected by the bath application of gamma-aminobutyric acid type A and N-methyl-D-aspartate receptor antagonists. However, both LTD and LTP were blocked by L-type Ca(2+)-channel antagonists. Thus the Ca(2+) influx associated with L-type channel activation mediates the induction of synaptic plasticity and may signal the pruning and subsequent stabilization of developing retinogeniculate connections.}, Author = {Ziburkus, Jok{\=u}bas and Dilger, Emily K and Lo, Fu-Sun and Guido, William}, Date-Added = {2013-05-28 18:22:11 +0000}, Date-Modified = {2013-05-28 20:01:55 +0000}, Doi = {10.1152/jn.90618.2008}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Thalamic Nuclei; visual system; LGN; Patch-Clamp Techniques; Voltage-Gated; Calcium Channels; development; synapse formation; plasticity; in vitro; synaptic; LTP; LTD; currOpinRvw}, Mesh = {2-Amino-5-phosphonovalerate; Age Factors; Animals; Animals, Newborn; Bicuculline; Biophysics; Calcium Channel Blockers; Dose-Response Relationship, Drug; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; Geniculate Bodies; Long-Term Potentiation; Long-Term Synaptic Depression; Nimodipine; Nitrendipine; Rats; Rats, Long-Evans; Retina; Synapses; Time Factors; Visual Pathways}, Month = {Dec}, Number = {6}, Pages = {3082-90}, Pmc = {PMC2804430}, pmid = {19776360}, Pst = {ppublish}, Title = {LTD and LTP at the developing retinogeniculate synapse}, Volume = {102}, Year = {2009}, url = {papers/Ziburkus_JNeurophysiol2009.pdf}} @article{Lo:2002, Abstract = {Using intracellular recordings in an isolated (in vitro) rat brain stem preparation, we examined the synaptic responses of developing relay neurons in the dorsal lateral geniculate nucleus (LGN). In newborn rats, strong stimulation of the optic tract (OT) evoked excitatory postsynaptic potentials (EPSPs) that gave rise to a sustained (300-1,300 ms), slow-decaying (<0.01 mV/s), depolarization (25-40 mV). Riding atop this response was a train of spikes of variable amplitude. We refer to this synaptically evoked event as a plateau potential. Pharmacology experiments indicate the plateau potential was mediated by the activation of high-threshold L-type Ca(2+) channels. Synaptic activation of the plateau potential relied on N-methyl-D-aspartate (NMDA) receptor-mediated activity and the spatial and/or temporal summation of retinally evoked EPSPs. Inhibitory postsynaptic responses (IPSPs) did not prevent the expression of the plateau potential. However, GABA(A) receptor activity modulated the intensity of optic tract stimulation needed to evoke the plateau potential, while GABA(B) receptor activity affected its duration. Expression of the plateau potential was developmentally regulated, showing a much higher incidence at P1-2 (90%) than at P19-20 (1%). This was in part due to the fact that developing relay cells show a greater degree of spatial summation than their mature counterparts, receiving input from as many as 7-12 retinal ganglion cells. Early spontaneous retinal activity is also likely to trigger the plateau potential. Repetitive stimulation of optic tract in a manner that approximated the high-frequency discharge of retinal ganglion cells led to a massive temporal summation of EPSPs and the activation of a sustained depolarization (>1 min) that was blocked by L-type Ca(2+) channel antagonists. These age-related changes in Ca(2+) signaling may contribute to the activity-dependent refinement of retinogeniculate connections.}, Author = {Lo, Fu-Sun and Ziburkus, Jokubas and Guido, William}, Date-Added = {2013-05-28 18:19:02 +0000}, Date-Modified = {2013-05-28 18:21:43 +0000}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Thalamic Nuclei; visual system; LGN; Patch-Clamp Techniques; Voltage-Gated; Calcium Channels; development; synapse formation; plasticity; GABA; rat; in vitro}, Mesh = {2-Amino-5-phosphonovalerate; Action Potentials; Animals; Baclofen; Bicuculline; Calcium; Calcium Channel Blockers; Calcium Channels, L-Type; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA Antagonists; Geniculate Bodies; Neurons; Nitrendipine; Rats; Rats, Sprague-Dawley; Receptors, GABA; Synapses}, Month = {Mar}, Number = {3}, Pages = {1175-85}, pmid = {11877491}, Pst = {ppublish}, Title = {Synaptic mechanisms regulating the activation of a Ca(2+)-mediated plateau potential in developing relay cells of the LGN}, Volume = {87}, Year = {2002}, url = {papers/Lo_JNeurophysiol2002.pdf}} @article{Krahe:2011, Abstract = {Monocular deprivation (MD) is a classic paradigm for experience-dependent cortical plasticity. One form is known as homeostatic plasticity, in which neurons innervated by the deprived eye show a remarkable capacity to compensate for degraded visual signals in an attempt to stabilize network activity. Although the evidence supporting homeostatic plasticity in visual cortex is extensive, it remains unclear whether neurons in subcortical visual structures respond to MD in a similar manner. Here we examined whether cells in the dorsal lateral geniculate nucleus (dLGN), the thalamic relay between the retina and visual cortex, show similar forms of experience-dependent homeostatic plasticity following MD. Two-week-old mice were monocularly deprived for a period of 5-7 d and miniature EPSCs (mEPSCs) were obtained from cells located in dLGN regions receiving input from the deprived or nondeprived eye. We found that MD promotes increases in the frequency and amplitude of mEPSCs and were restricted to the monocular segment contralateral to the deprived eye. These changes were accompanied by an increase in the probability of glutamate release at corticothalamic terminals that arise from the deprived visual cortex. Our findings indicate that homeostatic synaptic regulation from MD extends beyond cortical circuitry and shed light on how the brain modulates and integrates activity in the face of altered sensory experience.}, Author = {Krahe, Thomas E and Guido, William}, Date-Added = {2013-05-28 18:16:18 +0000}, Date-Modified = {2013-05-28 18:18:12 +0000}, Doi = {10.1523/JNEUROSCI.1173-11.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Thalamic Nuclei; visual system; mouse; LGN; Patch-Clamp Techniques; development; plasticity; Sensory Deprivation; homeostatic plasticity}, Mesh = {Analysis of Variance; Animals; Electric Stimulation; Electrophysiology; Excitatory Postsynaptic Potentials; Geniculate Bodies; Mice; Miniature Postsynaptic Potentials; Neuronal Plasticity; Neurons; Photic Stimulation; Sensory Deprivation; Vision, Monocular; Visual Pathways}, Month = {May}, Number = {18}, Pages = {6842-9}, Pmc = {PMC3319043}, pmid = {21543614}, Pst = {ppublish}, Title = {Homeostatic plasticity in the visual thalamus by monocular deprivation}, Volume = {31}, Year = {2011}, url = {papers/Krahe_JNeurosci2011.pdf}} @article{Dilger:2011, Abstract = {In developing cells of the mouse dorsal lateral geniculate nucleus (dLGN), synaptic responses evoked by optic tract (OT) stimulation give rise to long-lasting, high-amplitude depolarizations known as plateau potentials. These events are mediated by L-type Ca2+ channels and occur during early postnatal life, a time when retinogeniculate connections are remodelling. To better understand the relationship between L-type activity and dLGN development we used an in vitro thalamic slice preparation which preserves the retinal connections and intrinsic circuitry in dLGN and examined how synaptic responses evoked by OT stimulation lead to the activation of plateau potentials. By varying the strength and temporal frequency of OT stimulation we identified at least three factors that contribute to the developmental regulation of plateau activity: the degree of retinal convergence, the temporal pattern of retinal stimulation and the emergence of feed-forward inhibition. Before natural eye opening (postnatal day 14), the excitatory synaptic responses of relay cells receiving multiple retinal inputs summated in both the spatial and temporal domains to produce depolarizations sufficient to activate L-type activity. After eye opening, when inhibitory responses are fully developed, plateau activity was rarely evoked even with high temporal rates of OT stimulation. When the bulk of this inhibition was blocked by bath application of bicuculline, the incidence of plateau activity increased significantly. We also made use of a transgenic mouse that lacks the β3 subunit of the L-type Ca2+ channel. These mutants have far fewer membrane-bound Ca2+ channels and attenuated L-type activity. In β3 nulls, L-type plateau activity was rarely observed even at young ages when plateau activity prevails. Thus, in addition to the changing patterns of synaptic connectivity and retinal activity, the expression of L-type Ca2+ channels is a requisite component in the manifestation of plateau activity.}, Author = {Dilger, Emily K and Shin, Hee-Sup and Guido, William}, Date-Added = {2013-05-28 18:14:49 +0000}, Date-Modified = {2013-05-28 18:16:06 +0000}, Doi = {10.1113/jphysiol.2010.202499}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {Thalamic Nuclei; visual system; mouse; LGN; Patch-Clamp Techniques; Voltage-Gated; Calcium Channels; development; synapse formation; plasticity}, Mesh = {Animals; Animals, Newborn; Electric Stimulation; Evoked Potentials; Geniculate Bodies; Mice; Mice, Inbred C57BL; Mice, Transgenic; Synapses; Synaptic Potentials; Visual Pathways}, Month = {Feb}, Number = {Pt 4}, Pages = {919-37}, Pmc = {PMC3060370}, pmid = {21173075}, Pst = {ppublish}, Title = {Requirements for synaptically evoked plateau potentials in relay cells of the dorsal lateral geniculate nucleus of the mouse}, Volume = {589}, Year = {2011}, url = {papers/Dilger_JPhysiol2011.pdf}} @article{Bender:2003a, Abstract = {The excitatory feedforward projection from layer (L) 4 to L2/3 in rat primary somatosensory (S1) cortex exhibits precise, columnar topography that is critical for columnar processing of whisker inputs. Here, we characterize the development of axonal topography in this projection using single-cell reconstructions in S1 slices. In the mature projection [postnatal day (P) 14-26], axons of L4 cells extending into L2/3 were confined almost entirely to the home barrel column, consistent with previous results. At younger ages (P8-11), however, axonal topography was significantly less columnar, with a large proportion of branches innervating neighboring barrel columns representing adjacent whisker rows. Mature topography developed from this initial state by targeted axonal growth within the home column and by growth of barrel columns themselves. Raising rats with all or a subset of whiskers plucked from P8-9, manipulations that induce reorganization of functional whisker maps and synaptic depression at L4 to L2/3 synapses, did not alter normal anatomical development of L4 to L2/3 axons. Thus, development of this projection does not require normal sensory experience after P8, and deprivation-induced reorganization of whisker maps at this age is unlikely to involve physical remodeling of L4 to L2/3 axons.}, Author = {Bender, Kevin J and Rangel, Juliana and Feldman, Daniel E}, Date-Added = {2013-05-28 17:39:15 +0000}, Date-Modified = {2013-05-28 17:41:23 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {patterning; Somatosensory Cortex; barrels; axon guidance; synapse formation; Neocortex; development}, Mesh = {Action Potentials; Age Factors; Animals; Axons; Brain Mapping; Dendrites; Electric Stimulation; Lysine; Membrane Potentials; Neuronal Plasticity; Neurons; Patch-Clamp Techniques; Rats; Rats, Long-Evans; Sensory Deprivation; Somatosensory Cortex; Vibrissae}, Month = {Sep}, Number = {25}, Pages = {8759-70}, Pmc = {PMC3066032}, pmid = {14507976}, Pst = {ppublish}, Title = {Development of columnar topography in the excitatory layer 4 to layer 2/3 projection in rat barrel cortex}, Volume = {23}, Year = {2003}, url = {papers/Bender_JNeurosci2003a.pdf}} @article{Kovacs:2007, Abstract = {A key feature of memory processes is to link different input signals by association and to preserve this coupling at the level of synaptic connections. Late-phase long-term potentiation (L-LTP), a form of synaptic plasticity thought to encode long-term memory, requires gene transcription and protein synthesis. In this study, we report that a recently cloned coactivator of cAMP-response element-binding protein (CREB), called transducer of regulated CREB activity 1 (TORC1), contributes to this process by sensing the coincidence of calcium and cAMP signals in neurons and by converting it into a transcriptional response that leads to the synthesis of factors required for enhanced synaptic transmission. We provide evidence that TORC1 is involved in L-LTP maintenance at the Schaffer collateral-CA1 synapses in the hippocampus.}, Author = {Kov{\'a}cs, Kriszti{\'a}n A and Steullet, Pascal and Steinmann, Myriam and Do, Kim Q and Magistretti, Pierre J and Halfon, Olivier and Cardinaux, Jean-Ren{\'e}}, Date-Added = {2013-05-28 16:59:05 +0000}, Date-Modified = {2013-05-28 17:00:31 +0000}, Doi = {10.1073/pnas.0607524104}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {coincidence detector; plasticity; synapses; learning; memory; in vitro}, Mesh = {Active Transport, Cell Nucleus; Animals; Calcineurin; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Hippocampus; Long-Term Potentiation; Male; Mice; Neurons; RNA, Messenger; Rats; Synapses; Trans-Activators; Transcription Factors}, Month = {Mar}, Number = {11}, Pages = {4700-5}, Pmc = {PMC1838663}, pmid = {17360587}, Pst = {ppublish}, Title = {TORC1 is a calcium- and cAMP-sensitive coincidence detector involved in hippocampal long-term synaptic plasticity}, Volume = {104}, Year = {2007}, url = {papers/Kovács_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0607524104}} @article{Fino:2010, Abstract = {Corticostriatal projections constitute the main input to the basal ganglia, an ensemble of interconnected subcortical nuclei involved in procedural learning. Thus, long-term plasticity at corticostriatal synapses would provide a basic mechanism for the function of basal ganglia in learning and memory. We had previously reported the existence of a corticostriatal anti-Hebbian spike timing-dependent plasticity (STDP) at synapses onto striatal output neurons, the medium-sized spiny neurons. Here, we show that the blockade of GABAergic transmission reversed the time dependence of corticostriatal STDP. We explored the receptors and signalling mechanisms involved in the corticostriatal STDP. Although classical models for STDP propose NMDA receptors as the unique coincidence detector, the involvement of multiple coincidence detectors has also been demonstrated. Here, we show that corticostriatal STDP depends on distinct coincidence detectors. Specifically, long-term potentiation is dependent on NMDA receptor activation, while long-term depression requires distinct coincidence detectors: the phospholipase Cbeta (PLCbeta) and the inositol-trisphosphate receptor (IP3R)-gated calcium stores. Furthermore, we found that PLCbeta activation is controlled by group-I metabotropic glutamate receptors, type-1 muscarinic receptors and voltage-sensitive calcium channel activities. Activation of PLCbeta and IP3Rs leads to robust retrograde endocannabinoid signalling mediated by 2-arachidonoyl-glycerol and cannabinoid CB1 receptors. Interestingly, the same coincidence detectors govern the corticostriatal anti-Hebbian STDP and the Hebbian STDP reported at cortical synapses. Therefore, LTP and LTD induced by STDP at corticostriatal synapses are mediated by independent signalling mechanisms, each one being controlled by distinct coincidence detectors.}, Author = {Fino, Elodie and Paille, Vincent and Cui, Yihui and Morera-Herreras, Teresa and Deniau, Jean-Michel and Venance, Laurent}, Date-Added = {2013-05-28 16:54:37 +0000}, Date-Modified = {2013-05-28 16:58:07 +0000}, Doi = {10.1113/jphysiol.2010.188466}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {coincidence detector; currOpinRvw; synapses; plasticity}, Mesh = {Animals; Arachidonic Acids; Basal Ganglia; Calcium Channels; Cerebral Cortex; Endocannabinoids; Enzyme Activation; Enzyme Inhibitors; Excitatory Postsynaptic Potentials; Glycerides; Inositol 1,4,5-Trisphosphate Receptors; Neural Pathways; Neuronal Plasticity; Neurotransmitter Agents; Phospholipase C beta; Rats; Receptor, Cannabinoid, CB1; Receptor, Muscarinic M1; Receptors, Metabotropic Glutamate; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Synapses; Time Factors; gamma-Aminobutyric Acid}, Month = {Aug}, Number = {Pt 16}, Pages = {3045-62}, Pmc = {PMC2956944}, pmid = {20603333}, Pst = {ppublish}, Title = {Distinct coincidence detectors govern the corticostriatal spike timing-dependent plasticity}, Volume = {588}, Year = {2010}, url = {papers/Fino_JPhysiol2010.pdf}} @article{Bender:2006, Abstract = {Many cortical synapses exhibit spike timing-dependent plasticity (STDP) in which the precise timing of presynaptic and postsynaptic spikes induces synaptic strengthening [long-term potentiation (LTP)] or weakening [long-term depression (LTD)]. Standard models posit a single, postsynaptic, NMDA receptor-based coincidence detector for LTP and LTD components of STDP. We show instead that STDP at layer 4 to layer 2/3 synapses in somatosensory (S1) cortex involves separate calcium sources and coincidence detection mechanisms for LTP and LTD. LTP showed classical NMDA receptor dependence. LTD was independent of postsynaptic NMDA receptors and instead required group I metabotropic glutamate receptors and calcium from voltage-sensitive channels and IP3 receptor-gated stores. Downstream of postsynaptic calcium, LTD required retrograde endocannabinoid signaling, leading to presynaptic LTD expression, and also required activation of apparently presynaptic NMDA receptors. These LTP and LTD mechanisms detected firing coincidence on approximately 25 and approximately 125 ms time scales, respectively, and combined to implement the overall STDP rule. These findings indicate that STDP is not a unitary process and suggest that endocannabinoid-dependent LTD may be relevant to cortical map plasticity.}, Author = {Bender, Vanessa A and Bender, Kevin J and Brasier, Daniel J and Feldman, Daniel E}, Date-Added = {2013-05-28 16:31:50 +0000}, Date-Modified = {2013-05-28 16:32:27 +0000}, Doi = {10.1523/JNEUROSCI.0176-06.2006}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {coincidence detector; learning; memory; synapses; plasticity; currOpinRvw}, Mesh = {Action Potentials; Animals; Dizocilpine Maleate; Neuronal Plasticity; Piperidines; Pyrazoles; Rats; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate; Somatosensory Cortex; Time Factors}, Month = {Apr}, Number = {16}, Pages = {4166-77}, Pmc = {PMC3071735}, pmid = {16624937}, Pst = {ppublish}, Title = {Two coincidence detectors for spike timing-dependent plasticity in somatosensory cortex}, Volume = {26}, Year = {2006}, url = {papers/Bender_JNeurosci2006.pdf}} @article{Duguid:2006, Abstract = {Long-term plasticity typically relies on postsynaptic NMDA receptors to detect the coincidence of pre- and postsynaptic activity. Recent studies, however, have revealed forms of plasticity that depend on coincidence detection by presynaptic NMDA receptors. In the amygdala, cortical afferent associative presynaptic long-term potentiation (LTP) requires activation of presynaptic NMDA receptors by simultaneous thalamic and cortical afferents. Surprisingly, both types of afferent can also undergo postsynaptically induced NMDA-receptor-dependent LTP. In the neocortex, spike-timing-dependent long-term depression (LTD) requires simultaneous activation of presynaptic NMDA autoreceptors and retrograde signalling by endocannabinoids. In cerebellar LTD, presynaptic NMDA receptor activation suggests that similar presynaptic mechanisms may exist. Recent studies also indicate the existence of presynaptic coincidence detection that is independent of NMDA receptors, suggesting that such mechanisms have a widespread role in plasticity.}, Author = {Duguid, Ian and Sj{\"o}str{\"o}m, Per Jesper}, Date-Added = {2013-05-28 16:05:06 +0000}, Date-Modified = {2013-05-28 16:06:24 +0000}, Doi = {10.1016/j.conb.2006.05.008}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {currOpinRvw; synapses; plasticity; coincidence detector}, Mesh = {Action Potentials; Animals; Brain; Humans; Long-Term Potentiation; Neural Pathways; Neuronal Plasticity; Presynaptic Terminals; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Synaptic Transmission; Time Factors}, Month = {Jun}, Number = {3}, Pages = {312-22}, pmid = {16713246}, Pst = {ppublish}, Title = {Novel presynaptic mechanisms for coincidence detection in synaptic plasticity}, Volume = {16}, Year = {2006}, url = {papers/Duguid_CurrOpinNeurobiol2006.pdf}} @article{Wree:1983, Abstract = {The cerebral cortex of the albino mouse was examined by means of a quantitative method. An image analyzer was used in conjunction with an automatic scanning procedure to determine the grey level index in Nissl-stained sections. Computer plots of various ranges of grey level indices enabled delineation of cortical areas, from which cortical maps were graphically reconstructed. The cortical areal pattern is, in some regions, similar to the commonly used map of Caviness (1975) but differs considerably in other regions, especially in the temporal one. Furthermore, the primary visual cortex of the mouse was shown to be composed of two distinct cytoarchitectonic areas. The results of the study are discussed with respect to the literature on anatomical and functional localizations in the mouse cerebral cortex.}, Author = {Wree, A and Zilles, K and Schleicher, A}, Date-Added = {2013-04-23 18:06:37 +0000}, Date-Modified = {2013-04-23 18:07:00 +0000}, Journal = {Anat Embryol (Berl)}, Journal-Full = {Anatomy and embryology}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics; mouse}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Computers; Male; Mice; Temporal Lobe; Visual Cortex}, Number = {3}, Pages = {333-53}, pmid = {6869850}, Pst = {ppublish}, Title = {A quantitative approach to cytoarchitectonics. VIII. The areal pattern of the cortex of the albino mouse}, Volume = {166}, Year = {1983}, url = {papers/Wree_AnatEmbryol(Berl)1983.pdf}} @article{Campi:2010, Abstract = {In this study we examine and describe the neuroanatomical organization of sensory cortex in four rodents: laboratory Norway rats (Long Evans; Rattus norvegicus), wild-caught Norway rats (Rattus norvegicus), wild-caught California ground squirrels (Spermophilus beecheyi), and wild-caught Eastern gray squirrels (Sciurus carolinensis). Specifically, we examined the myeloarchitecture and cytochrome oxidase reactivity for several well-identified areas in visual cortex (areas 17, 18, and 19), somatosensory cortex (areas S1, S2 and PV), and auditory cortex [areas A1+AAF (R) and TA] and compared the percentage of dorsolateral cortex devoted to each of these areas. Our results demonstrate that squirrels have a larger mean percentage of dorsolateral cortex devoted to visual areas than rats. The difference is due to the greater percentage of cortex devoted to known areas such as area 17 and area 18 and not simply to a difference in the number of visual areas, which ultimately makes this distinction even more pronounced. Furthermore, both rat groups have a larger percentage of the dorsolateral cortex devoted to somatosensory and auditory cortical areas. Differences within groups were also observed. The arboreal squirrel had a larger mean percentage of dorsolateral cortex devoted to areas 17 and 18 compared with the terrestrial squirrel. The laboratory Norway rat had a larger percentage of dorsolateral cortex devoted to both somatosensory and auditory areas than the wild-caught Norway rat. Our results indicate that differences in sensory apparatus, use of sensory systems, and niche are reflected in the organization and size of cortical areas.}, Author = {Campi, Katharine L and Krubitzer, Leah}, Date-Added = {2013-04-23 18:04:55 +0000}, Date-Modified = {2013-04-23 18:05:02 +0000}, Doi = {10.1002/cne.22466}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Mesh = {Analysis of Variance; Animals; Animals, Laboratory; Animals, Wild; Body Weight; Brain Mapping; Circadian Rhythm; Functional Laterality; Life Style; Myelin Sheath; Rats; Rats, Long-Evans; Sciuridae; Species Specificity; Visual Cortex}, Month = {Nov}, Number = {22}, Pages = {4491-512}, Pmc = {PMC3432265}, pmid = {20886618}, Pst = {ppublish}, Title = {Comparative studies of diurnal and nocturnal rodents: differences in lifestyle result in alterations in cortical field size and number}, Volume = {518}, Year = {2010}, url = {papers/Campi_JCompNeurol2010.pdf}} @article{Campi:2011, Abstract = {In this study we examine the size of primary sensory areas in the neocortex and the cellular composition of area 17/V1 in three rodent groups: laboratory nocturnal Norway rats (Long-Evans; Rattus norvegicus), wild-caught nocturnal Norway rats (R. norvegicus), and laboratory diurnal Nile grass rats (Arvicanthis niloticus). Specifically, we used areal measures of myeloarchitecture of the primary sensory areas to compare area size and the isotropic fractionator method to estimate the number of neurons and nonneurons in area 17 in each species. Our results demonstrate that the percentage of cortex devoted to area 17 is significantly greater and the percentage of cortex devoted to S1 is significantly smaller in the diurnal Nile grass rat compared with the nocturnal Norway rat groups. Further, the laboratory rodent groups have a greater percentage of cortex devoted to auditory cortex compared with the wild-caught group. We also demonstrate that wild-caught rats have a greater density of neurons in area 17 compared to laboratory-reared animals. However, there were no other clear cellular composition differences in area 17 or differences in the percentage of brain weight devoted to area 17 between nocturnal and diurnal rats. Thus, there are differences in primary sensory area size between diurnal versus nocturnal and laboratory versus wild-caught rat groups and cellular density between wild-caught and laboratory rat groups. Our results demonstrate that the differences in the size and cellular composition of cortical areas do not fit with what would be expected based on brain scaling differences alone, and have a consistent relationship with lifestyle and sensory morphology.}, Author = {Campi, Katharine L and Collins, Christine E and Todd, William D and Kaas, Jon and Krubitzer, Leah}, Date-Added = {2013-04-23 18:03:41 +0000}, Date-Modified = {2013-04-23 18:04:05 +0000}, Doi = {10.1159/000324862}, Journal = {Brain Behav Evol}, Journal-Full = {Brain, behavior and evolution}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics; review literature}, Mesh = {Adaptation, Ocular; Animals; Animals, Domestic; Circadian Rhythm; Dark Adaptation; Female; Male; Neurons; Rats; Rats, Long-Evans; Species Specificity; Visual Cortex; Visual Pathways; Visual Perception}, Number = {2}, Pages = {116-30}, Pmc = {PMC3094678}, pmid = {21525748}, Pst = {ppublish}, Title = {Comparison of area 17 cellular composition in laboratory and wild-caught rats including diurnal and nocturnal species}, Volume = {77}, Year = {2011}, url = {papers/Campi_BrainBehavEvol2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000324862}} @article{Caviness:1975, Abstract = {The neocortex of the normal mouse has been subdivided into architectonic fields on the basis of its cellular and fiber patterns. The map of medial, retrohippocampal, frontal and insular regions is little different from that of Brodmann as modified in minor ways by Krieg. The map of parietal, occipital and temporal regions follows closely the major rearrangements introduced to Brodmann's map by Krieg. Krieg's map has been modified to give individual status to the barrel fields and to disignate occipital fields around the full circumference of field 17, and temporal fields circumferentially around field 41.}, Author = {Caviness, Jr, V S}, Date-Added = {2013-04-23 17:17:42 +0000}, Date-Modified = {2013-04-23 17:17:54 +0000}, Doi = {10.1002/cne.901640207}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Frontal Lobe; Hybridization, Genetic; Mice; Mice, Inbred Strains; Occipital Lobe; Parietal Lobe; Temporal Lobe}, Month = {Nov}, Number = {2}, Pages = {247-63}, pmid = {1184785}, Pst = {ppublish}, Title = {Architectonic map of neocortex of the normal mouse}, Volume = {164}, Year = {1975}, url = {papers/Caviness_JCompNeurol1975.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901640207}} @article{Reep:2009, Abstract = {A rodent model of directed attention has been developed based upon behavioral analysis of contralateral neglect, pharmacological manipulations, and anatomical analysis of neural circuitry. In each of these three domains the rodent model exhibits striking similarities to humans. We hypothesize that there is a specific thalamo-cortical-basal ganglia network that subserves spatial attentional functions. Key components of this network are medial agranular and posterior parietal cortex, dorsocentral striatum, and the lateral posterior thalamic nucleus. Several issues need to be addressed before we can hope to realistically understand or model the functions of this network. Among these are the roles of medial versus lateral posterior parietal cortex; cholinergic mechanisms in attention; interhemispheric interactions; the role of synchronous firing at the cortical, striatal, and thalamic levels; interactions between cortical and thalamic projections to the striatum; interactions between cortical and nigral inputs to the thalamus; the role of collicular inputs to the lateral posterior thalamic nucleus; the role of cerebral cortex versus superior colliculus in driving the motor output expressed as orienting behavior during directed attention; the extent to which the circuitry we describe for directed attention also plays a role in other forms of attention.}, Author = {Reep, Roger L and Corwin, James V}, Date-Added = {2013-04-17 21:10:26 +0000}, Date-Modified = {2014-09-16 16:12:55 +0000}, Doi = {10.1016/j.nlm.2008.08.010}, Journal = {Neurobiol Learn Mem}, Journal-Full = {Neurobiology of learning and memory}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics; rat; Posterior parietal cortex; ppc; Spatial Behavior; navigation; Motor Activity; grid cells; Decision Making; goal directed behavior; retrosplenial cortex}, Mesh = {Acetylcholine; Animals; Attention; Basal Ganglia; Cortical Synchronization; Disease Models, Animal; Functional Laterality; Humans; Motor Activity; Neural Pathways; Neurons; Orientation; Parietal Lobe; Perceptual Disorders; Tectum Mesencephali; Thalamus}, Month = {Feb}, Number = {2}, Pages = {104-13}, pmid = {18824116}, Pst = {ppublish}, Title = {Posterior parietal cortex as part of a neural network for directed attention in rats}, Volume = {91}, Year = {2009}, url = {papers/Reep_NeurobiolLearnMem2009.pdf}} @article{Kaas:2011, Abstract = {In Prosimian primates, New World monkeys, and Old World monkeys microstimulation with half second trains of electrical pulses identifies separate zones in posterior parietal cortex (PPC) where reaching, defensive, grasping, and other complex movements can be evoked. Each functional zone receives a different pattern of visual and somatosensory inputs, and projects preferentially to functionally matched parts of motor and premotor cortex. As PPC is a relatively small portion of cortex in most mammals, including the close relatives of primates, we suggest that a larger, more significant PPC emerged with the first primates as a region where several ethologically relevant behaviors could be initiated by sensory and intrinsic signals, and mediated via connections with premotor and motor cortex. While several classes of PPC modules appear to be retained by all primates, elaboration and differentiation of these modules likely occurred in some primates, especially humans.}, Author = {Kaas, Jon H and Gharbawie, Omar A and Stepniewska, Iwona}, Date-Added = {2013-04-17 21:08:08 +0000}, Date-Modified = {2013-04-23 17:56:33 +0000}, Doi = {10.3389/fnana.2011.00034}, Journal = {Front Neuroanat}, Journal-Full = {Frontiers in neuroanatomy}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Pages = {34}, Pmc = {PMC3116136}, pmid = {21716641}, Pst = {ppublish}, Title = {The organization and evolution of dorsal stream multisensory motor pathways in primates}, Volume = {5}, Year = {2011}, url = {papers/Kaas_FrontNeuroanat2011.pdf}} @book{Chalupa:2008, Address = {Cambridge, Mass.}, Annote = {LDR 01428cam 2200337 a 4500 001 15090115 005 20090828092700.0 008 071121s2008 mauaf b 001 0 eng 906 $a7$bcbc$corignew$d1$eecip$f20$gy-gencatlg 925 0 $aacquire$b2 shelf copies$xpolicy default 955 $ajb04 2007-11-21$ijb04 2007-11-21$ejb04 2007-11-21 to Dewey$aaa07 2007-11-29$aps04 2008-07-08 1 copy rec'd., to CIP ver.$fsc02 2008-07-24 Z-CipVer$gsc02 2008-07-24 to BCCD$alg08 2008-09-09 copy 2 added 010 $a 2007047445 015 $aGBA889303$2bnb 016 7 $a014669647$2Uk 020 $a9780262033817 (hardcover : alk. paper) 020 $a026203381X (hardcover : alk. paper) 035 $a(OCoLC)ocn182662502 035 $a(OCoLC)182662502 040 $aDLC$cDLC$dBTCTA$dBAKER$dYDXCP$dOCLCG$dC#P$dUKM$dDLC 050 00 $aQL737.R6$bE94 2008 082 00 $a573.8/819353$222 245 00 $aEye, retina, and visual system of the mouse /$cedited by Leo M. Chalupa and Robert W. Williams. 260 $aCambridge, Mass. :$bMIT Press,$cc2008. 300 $axii, 754 p., [48] p. of plates :$bill. (some col.) ;$c29 cm. 504 $aIncludes bibliographical references and index. 650 0 $aMice$xSense organs. 650 0 $aEye. 650 0 $aVisual pathways. 700 1 $aChalupa, Leo M. 700 1 $aWilliams, Robert W.,$d1952- 856 41 $3Table of contents only$uhttp://www.loc.gov/catdir/toc/ecip085/2007047445.html }, Author = {Chalupa, Leo M and Williams, Robert W.}, Call-Number = {QL737.R6}, Date-Added = {2013-04-17 20:54:07 +0000}, Date-Modified = {2013-04-23 17:56:13 +0000}, Dewey-Call-Number = {573.8/819353}, Genre = {Mice}, Isbn = {9780262033817 (hardcover : alk. paper)}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Library-Id = {2007047445}, Publisher = {MIT Press}, Title = {Eye, retina, and visual system of the mouse}, eprint = {http://www.loc.gov/catdir/toc/ecip085/2007047445.html}, Year = {2008}} @book{Paxinos:1995, Address = {San Diego}, Annote = {LDR 01198cam 2200313 a 4500 001 4906797 005 20030709200427.0 008 940621s1995 caua b 001 0 eng 035 $9(DLC) 94026442 906 $a7$bcbc$corignew$d1$eocip$f19$gy-gencatlg 955 $apc05 to ja00 06-21-94; jb09 06-21-94; jb02 06-23-94; aa07 06-23-94; CIP ver. pv06 12-08-94 010 $a 94026442 020 $a0125476353 (acid-free paper) 040 $aDLC$cDLC$dDLC 050 00 $aQL937$b.R33 1995 082 00 $a599.32/33$220 245 04 $aThe rat nervous system /$cedited by George Paxinos. 250 $a2nd ed. 260 $aSan Diego :$bAcademic Press,$cc1995. 300 $axvii, 1136 p. :$bill. ;$c29 cm. 504 $aIncludes bibliographical references and index. 650 0 $aRats$xAnatomy. 650 0 $aBrain$xAnatomy. 650 0 $aRats$xNervous system. 700 1 $aPaxinos, George,$d1944- 856 42 $3Publisher description$uhttp://www.loc.gov/catdir/description/els032/94026442.html 856 41 $3Table of contents$uhttp://www.loc.gov/catdir/toc/els032/94026442.html 920 $a** LC HAS REQ'D # OF SHELF COPIES ** 991 $bc-GenColl$hQL937$i.R33 1995$p00055111315$tCopy 1$wBOOKS }, Author = {Paxinos, George}, Call-Number = {QL937}, Date-Added = {2013-04-17 20:45:25 +0000}, Date-Modified = {2013-04-23 17:55:51 +0000}, Dewey-Call-Number = {599.32/33}, Edition = {2nd ed}, Genre = {Rats}, Isbn = {0125476353 (acid-free paper)}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Library-Id = {94026442}, Publisher = {Academic Press}, Title = {The rat nervous system}, eprint = {http://www.loc.gov/catdir/description/els032/94026442.html}, Year = {1995}} @book{Paxinos:2004, Address = {Amsterdam}, Annote = {LDR 01232cam 2200289 a 4500 001 13582666 005 20041223075507.0 008 040504s2004 ne a b 001 0 eng 906 $a7$bcbc$corigcop$d2$encip$f20$gy-gencatlg 925 0 $aacquire$b2 shelf copies$xpolicy default 955 $apv21 2004-05-04 Preprocessor two copies to ASCD$ajc41 2004-05-11 sent to Bio-Ag$ajb00 2004-05-12 bk. rec.$cjb17 2004-06-22$djb09 2004-06-30$ejb18 2004-07-28 Copies 1-2 to Dewey$aaa07 2004-07-29 010 $a 2004270372 020 $a0125476388 (alk. paper) 040 $aDLC$cDLC$dDLC 050 00 $aQL937$b.R33 2004 082 00 $a573.8/19352$222 245 04 $aThe rat nervous system /$cedited by George Paxinos. 250 $a3rd ed. 260 $aAmsterdam ;$aBoston :$bElsevier Academic Press,$cc2004. 300 $axvii, 1309 p. :$bill. (some col.) ;$c29 cm. 504 $aIncludes bibliographical references and index. 650 0 $aRats$xAnatomy. 650 0 $aBrain$xAnatomy. 650 0 $aRats$xNervous system. 700 1 $aPaxinos, George,$d1944- 856 41 $3Table of contents$uhttp://www.loc.gov/catdir/toc/els051/2004270372.html 856 42 $3Publisher description$uhttp://www.loc.gov/catdir/description/els051/2004270372.html }, Author = {Paxinos, George}, Call-Number = {QL937}, Date-Added = {2013-04-17 20:45:19 +0000}, Date-Modified = {2013-04-23 17:55:42 +0000}, Dewey-Call-Number = {573.8/19352}, Edition = {3rd ed}, Genre = {Rats}, Isbn = {0125476388 (alk. paper)}, Keywords = {neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Library-Id = {2004270372}, Publisher = {Elsevier Academic Press}, Title = {The rat nervous system}, eprint = {http://www.loc.gov/catdir/toc/els051/2004270372.html}, Year = {2004}} @article{Lim:2012, Abstract = {We have mapped intracortical activity in vivo independent of sensory input using arbitrary point channelrhodopsin-2 (ChR2) stimulation and regional voltage sensitive dye imaging in B6.Cg-Tg (Thy1-COP4/EYFP)18Gfng/J transgenic mice. Photostimulation of subsets of deep layer pyramidal neurons within forelimb, barrel, or visual primary sensory cortex led to downstream cortical maps that were dependent on synaptic transmission and were similar to peripheral sensory stimulation. ChR2-evoked maps confirmed homotopic connections between hemispheres and intracortical sensory and motor cortex connections. This ability of optogentically activated subpopulations of neurons to drive appropriate downstream maps suggests that mechanisms exist to allow prototypical cortical maps to self-assemble from the stimulation of neuronal subsets. Using this principle of map self-assembly, we employed ChR2 point stimulation to map connections between cortical areas that are not selectively activated by peripheral sensory stimulation or behavior. Representing the functional cortical regions as network nodes, we identified asymmetrical connection weights in individual nodes and identified the parietal association area as a network hub. Furthermore, we found that the strength of reciprocal intracortical connections between primary and secondary sensory areas are unequal, with connections from primary to secondary sensory areas being stronger than the reciprocal.}, Author = {Lim, Diana H and Mohajerani, Majid H and Ledue, Jeffrey and Boyd, Jamie and Chen, Shangbin and Murphy, Timothy H}, Date-Added = {2013-04-01 16:18:07 +0000}, Date-Modified = {2013-04-01 16:18:44 +0000}, Doi = {10.3389/fncir.2012.00011}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {downloads}, Pages = {11}, Pmc = {PMC3304170}, pmid = {22435052}, Pst = {ppublish}, Title = {In vivo Large-Scale Cortical Mapping Using Channelrhodopsin-2 Stimulation in Transgenic Mice Reveals Asymmetric and Reciprocal Relationships between Cortical Areas}, Volume = {6}, Year = {2012}, url = {papers/Lim_FrontNeuralCircuits2012.pdf}} @article{Hong:2012, Abstract = {Neurons are interconnected with extraordinary precision to assemble a functional nervous system. Compared to axon guidance, far less is understood about how individual pre- and postsynaptic partners are matched. To ensure the proper relay of olfactory information in the fruitfly Drosophila, axons of ∼50 classes of olfactory receptor neurons (ORNs) form one-to-one connections with dendrites of ∼50 classes of projection neurons (PNs). Here, using genetic screens, we identified two evolutionarily conserved, epidermal growth factor (EGF)-repeat containing transmembrane Teneurin proteins, Ten-m and Ten-a, as synaptic-partner-matching molecules between PN dendrites and ORN axons. Ten-m and Ten-a are highly expressed in select PN-ORN matching pairs. Teneurin loss- and gain-of-function cause specific mismatching of select ORNs and PNs. Finally, Teneurins promote homophilic interactions in vitro, and Ten-m co-expression in non-partner PNs and ORNs promotes their ectopic connections in vivo. We propose that Teneurins instruct matching specificity between synaptic partners through homophilic attraction.}, Author = {Hong, Weizhe and Mosca, Timothy J and Luo, Liqun}, Date-Added = {2013-04-01 16:18:07 +0000}, Date-Modified = {2013-04-01 16:18:44 +0000}, Doi = {10.1038/nature10926}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Axons; Drosophila Proteins; Drosophila melanogaster; Olfactory Pathways; Olfactory Receptor Neurons; Protein Binding; RNA Interference; Receptors, Cell Surface; Smell; Synapses; Tenascin}, Month = {Apr}, Number = {7393}, Pages = {201-7}, Pmc = {PMC3345284}, pmid = {22425994}, Pst = {epublish}, Title = {Teneurins instruct synaptic partner matching in an olfactory map}, Volume = {484}, Year = {2012}, url = {papers/Hong_Nature2012.pdf}} @article{Derecki:2012a, Abstract = {Rett syndrome is an X-linked autism spectrum disorder. The disease is characterized in most cases by mutation of the MECP2 gene, which encodes a methyl-CpG-binding protein. Although MECP2 is expressed in many tissues, the disease is generally attributed to a primary neuronal dysfunction. However, as shown recently, glia, specifically astrocytes, also contribute to Rett pathophysiology. Here we examine the role of another form of glia, microglia, in a murine model of Rett syndrome. Transplantation of wild-type bone marrow into irradiation-conditioned Mecp2-null hosts resulted in engraftment of brain parenchyma by bone-marrow-derived myeloid cells of microglial phenotype, and arrest of disease development. However, when cranial irradiation was blocked by lead shield, and microglial engraftment was prevented, disease was not arrested. Similarly, targeted expression of MECP2 in myeloid cells, driven by Lysm(cre) on an Mecp2-null background, markedly attenuated disease symptoms. Thus, through multiple approaches, wild-type Mecp2-expressing microglia within the context of an Mecp2-null male mouse arrested numerous facets of disease pathology: lifespan was increased, breathing patterns were normalized, apnoeas were reduced, body weight was increased to near that of wild type, and locomotor activity was improved. Mecp2(+/-) females also showed significant improvements as a result of wild-type microglial engraftment. These benefits mediated by wild-type microglia, however, were diminished when phagocytic activity was inhibited pharmacologically by using annexin V to block phosphatydilserine residues on apoptotic targets, thus preventing recognition and engulfment by tissue-resident phagocytes. These results suggest the importance of microglial phagocytic activity in Rett syndrome. Our data implicate microglia as major players in the pathophysiology of this devastating disorder, and suggest that bone marrow transplantation might offer a feasible therapeutic approach for it.}, Author = {Derecki, No{\"e}l C and Cronk, James C and Lu, Zhenjie and Xu, Eric and Abbott, Stephen B G and Guyenet, Patrice G and Kipnis, Jonathan}, Date-Added = {2013-04-01 16:18:07 +0000}, Date-Modified = {2013-04-01 16:18:44 +0000}, Doi = {10.1038/nature10907}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Annexin A5; Apoptosis; Body Weight; Bone Marrow Transplantation; Brain; Disease Models, Animal; Disease Progression; Female; Insulin-Like Growth Factor I; Locomotion; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Inbred C57BL; Microglia; Phagocytosis; Phosphatidylserines; Respiration; Rett Syndrome; Rotarod Performance Test}, Month = {Apr}, Number = {7392}, Pages = {105-9}, Pmc = {PMC3321067}, pmid = {22425995}, Pst = {epublish}, Title = {Wild-type microglia arrest pathology in a mouse model of Rett syndrome}, Volume = {484}, Year = {2012}, url = {papers/Derecki_Nature2012a.pdf}} @article{Mosca:2012, Abstract = {Synapse assembly requires trans-synaptic signals between the pre- and postsynapse, but our understanding of the essential organizational molecules involved in this process remains incomplete. Teneurin proteins are conserved, epidermal growth factor (EGF)-repeat-containing transmembrane proteins with large extracellular domains. Here we show that two Drosophila Teneurins, Ten-m and Ten-a, are required for neuromuscular synapse organization and target selection. Ten-a is presynaptic whereas Ten-m is mostly postsynaptic; neuronal Ten-a and muscle Ten-m form a complex in vivo. Pre- or postsynaptic Teneurin perturbations cause severe synapse loss and impair many facets of organization trans-synaptically and cell autonomously. These include defects in active zone apposition, release sites, membrane and vesicle organization, and synaptic transmission. Moreover, the presynaptic microtubule and postsynaptic spectrin cytoskeletons are severely disrupted, suggesting a mechanism whereby Teneurins organize the cytoskeleton, which in turn affects other aspects of synapse development. Supporting this, Ten-m physically interacts with α-Spectrin. Genetic analyses of teneurin and neuroligin reveal that they have differential roles that synergize to promote synapse assembly. Finally, at elevated endogenous levels, Ten-m regulates target selection between specific motor neurons and muscles. Our study identifies the Teneurins as a key bi-directional trans-synaptic signal involved in general synapse organization, and demonstrates that proteins such as these can also regulate target selection.}, Author = {Mosca, Timothy J and Hong, Weizhe and Dani, Vardhan S and Favaloro, Vincenzo and Luo, Liqun}, Date-Added = {2013-04-01 16:18:07 +0000}, Date-Modified = {2013-04-01 16:18:44 +0000}, Doi = {10.1038/nature10923}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Biological Markers; Cell Adhesion Molecules, Neuronal; Cytoskeleton; Drosophila Proteins; Drosophila melanogaster; Gene Expression Regulation; Larva; Microtubule-Associated Proteins; Muscles; Neuromuscular Junction; Neurons; Receptors, Cell Surface; Synapses; Synaptic Transmission; Tenascin}, Month = {Apr}, Number = {7393}, Pages = {237-41}, Pmc = {PMC3326183}, pmid = {22426000}, Pst = {epublish}, Title = {Trans-synaptic Teneurin signalling in neuromuscular synapse organization and target choice}, Volume = {484}, Year = {2012}, url = {papers/Mosca_Nature2012.pdf}} @article{Grienberger:2012, Abstract = {Calcium ions generate versatile intracellular signals that control key functions in all types of neurons. Imaging calcium in neurons is particularly important because calcium signals exert their highly specific functions in well-defined cellular subcompartments. In this Primer, we briefly review the general mechanisms of neuronal calcium signaling. We then introduce the calcium imaging devices, including confocal and two-photon microscopy as well as miniaturized devices that are used in freely moving animals. We provide an overview of the classical chemical fluorescent calcium indicators and of the protein-based genetically encoded calcium indicators. Using application examples, we introduce new developments in the field, such as calcium imaging in awake, behaving animals and the use of calcium imaging for mapping single spine sensory inputs in cortical neurons in vivo. We conclude by providing an outlook on the prospects of calcium imaging for the analysis of neuronal signaling and plasticity in various animal models.}, Author = {Grienberger, Christine and Konnerth, Arthur}, Date-Added = {2013-04-01 16:18:07 +0000}, Date-Modified = {2013-04-01 16:18:44 +0000}, Doi = {10.1016/j.neuron.2012.02.011}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {downloads}, Mesh = {Aequorin; Animals; Calcium; Calcium Channels; Calcium Signaling; Diagnostic Imaging; Humans; Luminescent Agents; Neurons; Photons; Receptors, Ionotropic Glutamate}, Month = {Mar}, Number = {5}, Pages = {862-85}, pmid = {22405199}, Pst = {ppublish}, Title = {Imaging calcium in neurons}, Volume = {73}, Year = {2012}, url = {papers/Grienberger_Neuron2012.pdf}} @article{McGinley:2012, Abstract = {Broadband transient sounds, such as clicks and consonants, activate a traveling wave in the cochlea. This wave evokes firing in auditory nerve fibers that are tuned to high frequencies several milliseconds earlier than in fibers tuned to low frequencies. Despite this substantial traveling wave delay, octopus cells in the brainstem receive broadband input and respond to clicks with submillisecond temporal precision. The dendrites of octopus cells lie perpendicular to the tonotopically organized array of auditory nerve fibers, placing the earliest arriving inputs most distally and the latest arriving closest to the soma. Here, we test the hypothesis that the topographic arrangement of synaptic inputs on dendrites of octopus cells allows octopus cells to compensate the traveling wave delay. We show that in mice the full cochlear traveling wave delay is 1.6 ms. Because the dendrites of each octopus cell spread across approximately one-third of the tonotopic axis, a click evokes a soma-directed sweep of synaptic input lasting 0.5 ms in individual octopus cells. Morphologically and biophysically realistic, computational models of octopus cells show that soma-directed sweeps with durations matching in vivo measurements result in the largest and sharpest somatic EPSPs. A low input resistance and activation of a low-voltage-activated potassium conductance that are characteristic of octopus cells are important determinants of sweep sensitivity. We conclude that octopus cells have dendritic morphologies and biophysics tailored to accomplish the precise encoding of broadband transient sounds.}, Author = {McGinley, Matthew J and Liberman, M Charles and Bal, Ramazan and Oertel, Donata}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1523/JNEUROSCI.0272-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Acoustic Stimulation; Animals; Auditory Pathways; Brain Waves; Cochlea; Cochlear Nerve; Cochlear Nucleus; Dendrites; Excitatory Postsynaptic Potentials; Female; Humans; Male; Mice; Mice, Inbred CBA; Mice, Inbred ICR; Models, Neurological}, Month = {Jul}, Number = {27}, Pages = {9301-11}, Pmc = {PMC3417346}, pmid = {22764237}, Pst = {ppublish}, Title = {Generating synchrony from the asynchronous: compensation for cochlear traveling wave delays by the dendrites of individual brainstem neurons}, Volume = {32}, Year = {2012}, url = {papers/McGinley_JNeurosci2012.pdf}} @article{Nataraj:2011, Abstract = {Different neocortical regions are functionally specialized, but whether this specialization is reflected in the forms of plasticity present during developmental critical periods (CPs) is largely unknown. In rodent visual cortex, we recently showed that a form of intrinsic plasticity [LTP of intrinsic excitability (LTP-IE)] in the monocular region of the primary visual cortex (V1M) plays an important role in modulating cortical responsiveness following visual deprivation. Here we ask whether LTP-IE is present and similarly regulated by visual experience in the binocular region of the primary visual cortex (V1B), where inputs from the two eyes compete during the CP. In contrast to V1M, where LTP-IE is present throughout the CP, in V1B LTP-IE was only transiently expressed at the onset of the CP. Also distinct from V1M, brief monocular deprivation (MD) was unable to modulate LTP-IE magnitude in V1B, and even binocular deprivation (the equivalent of MD in V1M) could only influence LTP-IE expression during a narrow time window at the peak of the CP. Finally, we asked whether these differences depend on differences in sensory activation of the two areas during development. MD of ipsilateral inputs from before eye opening (to reduce competitive interactions) did not affect the pattern of LTP-IE expression in V1B. Further, the differences in plasticity in the two cortical areas persisted when animals were reared in the dark to remove all patterned visual input. Thus neocortical LTP-IE expression shows dramatic regional and temporal differentiation, and these differences are not driven by differences in sensory experience.}, Author = {Nataraj, Kiran and Turrigiano, Gina}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-08-27 20:02:04 +0000}, Doi = {10.1523/JNEUROSCI.4455-11.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads; currOpinRvw}, Mesh = {Age Factors; Analysis of Variance; Animals; Animals, Newborn; Biophysics; Critical Period (Psychology); Dark Adaptation; Electric Stimulation; Female; Functional Laterality; Long-Term Potentiation; Lysine; Male; Patch-Clamp Techniques; Rats; Rats, Long-Evans; Sensory Deprivation; Time Factors; Visual Cortex}, Month = {Dec}, Number = {49}, Pages = {17932-40}, Pmc = {PMC3272675}, pmid = {22159108}, Pst = {ppublish}, Title = {Regional and temporal specificity of intrinsic plasticity mechanisms in rodent primary visual cortex}, Volume = {31}, Year = {2011}, url = {papers/Nataraj_JNeurosci2011.pdf}} @article{Grant:2012, Abstract = {In this review we discuss recent advances in the understanding of corticothalamic axon guidance; patterning of the early telencephalon, the sequence and choreography of the development of projections from subplate, layers 5 and 6. These cortical subpopulations display different axonal outgrowth kinetics and innervate distinct thalamic nuclei in a temporal pattern determined by cortical layer identity and subclass specificity. Guidance by molecular cues, structural cues, and activity-dependent mechanisms contribute to this development. There is a substantial rearrangement of the corticofugal connectivity outside the thalamus at the border of and within the reticular thalamic nucleus, a region that shares some of the characteristics of the cortical subplate during development. The early transient circuits are not well understood, nor the extent to which this developmental pattern may be driven by peripheral sensory activity. We hypothesize that transient circuits during embryonic and early postnatal development are critical in the matching of the cortical and thalamic representations and forming the cortical circuits in the mature brain.}, Author = {Grant, Eleanor and Hoerder-Suabedissen, Anna and Moln{\'a}r, Zolt{\'a}n}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.3389/fnins.2012.00053}, Journal = {Front Neurosci}, Journal-Full = {Frontiers in neuroscience}, Keywords = {downloads}, Pages = {53}, Pmc = {PMC3343305}, pmid = {22586359}, Pst = {ppublish}, Title = {Development of the corticothalamic projections}, Volume = {6}, Year = {2012}, url = {papers/Grant_FrontNeurosci2012.pdf}} @article{Blandina:2012, Abstract = {Histamine axons originate from a single source, the tuberomamillary nucleus (TMN) of the posterior hypothalamus, to innervate almost all central nervous system (CNS) regions. This feature, a compact cell group with widely distributed fibers, resembles that of other amine systems, such as noradrenaline or serotonin, and is consistent with a function for histamine over a host of physiological processes, including the regulation of the sleep-wake cycle, appetite, endocrine homeostasis, body temperature, pain perception, learning, memory, and emotion. An important question is whether these diverse physiological roles are served by different histamine neuronal subpopulation. While the histamine system is generally regarded as one single functional unit that provides histamine throughout the brain, evidence is beginning to accumulate in favor of heterogeneity of histamine neurons. The aim of this review is to summarize experimental evidence demonstrating that histamine neurons are heterogeneous, organized into functionally distinct circuits, impinging on different brain regions, and displaying selective control mechanisms. This could imply independent functions of subsets of histamine neurons according to their respective origin and terminal projections.}, Author = {Blandina, Patrizio and Munari, Leonardo and Provensi, Gustavo and Passani, Maria B}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.3389/fnsys.2012.00033}, Journal = {Front Syst Neurosci}, Journal-Full = {Frontiers in systems neuroscience}, Keywords = {downloads}, Pages = {33}, Pmc = {PMC3343474}, pmid = {22586376}, Pst = {ppublish}, Title = {Histamine neurons in the tuberomamillary nucleus: a whole center or distinct subpopulations?}, Volume = {6}, Year = {2012}, url = {papers/Blandina_FrontSystNeurosci2012.pdf}} @article{Stanley:2012, Abstract = {Medical applications of nanotechnology typically focus on drug delivery and biosensors. Here, we combine nanotechnology and bioengineering to demonstrate that nanoparticles can be used to remotely regulate protein production in vivo. We decorated a modified temperature-sensitive channel, TRPV1, with antibody-coated iron oxide nanoparticles that are heated in a low-frequency magnetic field. When local temperature rises, TRPV1 gates calcium to stimulate synthesis and release of bioengineered insulin driven by a Ca(2+)-sensitive promoter. Studying tumor xenografts expressing the bioengineered insulin gene, we show that exposure to radio waves stimulates insulin release from the tumors and lowers blood glucose in mice. We further show that cells can be engineered to synthesize genetically encoded ferritin nanoparticles and inducibly release insulin. These approaches provide a platform for using nanotechnology to activate cells.}, Author = {Stanley, Sarah A and Gagner, Jennifer E and Damanpour, Shadi and Yoshida, Mitsukuni and Dordick, Jonathan S and Friedman, Jeffrey M}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1126/science.1216753}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {downloads}, Mesh = {Animals; Bioengineering; Blood Glucose; Calcium; Embryonic Stem Cells; Epitopes; Ferric Compounds; Ferritins; HEK293 Cells; Hot Temperature; Humans; Insulin; Male; Metal Nanoparticles; Mice; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; PC12 Cells; Radio Waves; Rats; Recombinant Fusion Proteins; TRPV Cation Channels; Transfection; Transplantation, Heterologous}, Month = {May}, Number = {6081}, Pages = {604-8}, pmid = {22556257}, Pst = {ppublish}, Title = {Radio-wave heating of iron oxide nanoparticles can regulate plasma glucose in mice}, Volume = {336}, Year = {2012}, url = {papers/Stanley_Science2012.pdf}} @article{Swindell:2006a, Abstract = {Rx is a homeobox-containing gene that is critical for vertebrate eye development. Its expression domain delineates a field of cells from which the retina and the ventral hypothalamus develop. The 5' upstream regulatory sequences of the medaka fish Rx gene are functionally conserved during evolution to a degree that they direct gene expression into the Rx-expressing field of cells in mice. Using these sequences, we made a Cre line that can be used for inactivation of gene expression in the developing retina.}, Author = {Swindell, Eric C and Bailey, Travis J and Loosli, Felix and Liu, Chaomei and Amaya-Manzanares, Felipe and Mahon, Kathleen A and Wittbrodt, Joachim and Jamrich, Milan}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1002/dvg.20225}, Journal = {Genesis}, Journal-Full = {Genesis (New York, N.Y. : 2000)}, Keywords = {downloads}, Mesh = {Alleles; Animals; Eye Proteins; Gene Expression Regulation, Developmental; Genes, Homeobox; Genes, Reporter; Green Fluorescent Proteins; Homeodomain Proteins; Integrases; Lac Operon; Mice; Mice, Transgenic; Oryzias; Retina}, Month = {Aug}, Number = {8}, Pages = {361-3}, pmid = {16850473}, Pst = {ppublish}, Title = {Rx-Cre, a tool for inactivation of gene expression in the developing retina}, Volume = {44}, Year = {2006}, url = {papers/Swindell_Genesis2006a.pdf}} @article{Li:2012a, Abstract = {A fundamental feature of the mammalian neocortex is its columnar organization. In the visual cortex, functional columns consisting of neurons with similar orientation preferences have been characterized extensively, but how these columns are constructed during development remains unclear. The radial unit hypothesis posits that the ontogenetic columns formed by clonally related neurons migrating along the same radial glial fibre during corticogenesis provide the basis for functional columns in adult neocortex. However, a direct correspondence between the ontogenetic and functional columns has not been demonstrated. Here we show that, despite the lack of a discernible orientation map in mouse visual cortex, sister neurons in the same radial clone exhibit similar orientation preferences. Using a retroviral vector encoding green fluorescent protein to label radial clones of excitatory neurons, and in vivo two-photon calcium imaging to measure neuronal response properties, we found that sister neurons preferred similar orientations whereas nearby non-sister neurons showed no such relationship. Interestingly, disruption of gap junction coupling by viral expression of a dominant-negative mutant of Cx26 (also known as Gjb2) or by daily administration of a gap junction blocker, carbenoxolone, during the first postnatal week greatly diminished the functional similarity between sister neurons, suggesting that the maturation of ontogenetic into functional columns requires intercellular communication through gap junctions. Together with the recent finding of preferential excitatory connections among sister neurons, our results support the radial unit hypothesis and unify the ontogenetic and functional columns in the visual cortex.}, Author = {Li, Ye and Lu, Hui and Cheng, Pei-lin and Ge, Shaoyu and Xu, Huatai and Shi, Song-Hai and Dan, Yang}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-08-28 16:41:13 +0000}, Doi = {10.1038/nature11110}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {development; visual system; Selection; Cooperative Behavior; topographic map; Visual Cortex}, Mesh = {Animals; Animals, Newborn; Carbenoxolone; Cell Communication; Clone Cells; Connexins; Female; Gap Junctions; Male; Mice; Mice, Inbred C57BL; Models, Neurological; Neurons; Visual Cortex}, Month = {Jun}, Number = {7401}, Pages = {118-21}, Pmc = {PMC3375857}, pmid = {22678292}, Pst = {epublish}, Title = {Clonally related visual cortical neurons show similar stimulus feature selectivity}, Volume = {486}, Year = {2012}, url = {papers/Li_Nature2012.pdf}} @article{Yu:2012a, Abstract = {Radial glial cells are the primary neural progenitor cells in the developing neocortex. Consecutive asymmetric divisions of individual radial glial progenitor cells produce a number of sister excitatory neurons that migrate along the elongated radial glial fibre, resulting in the formation of ontogenetic columns. Moreover, sister excitatory neurons in ontogenetic columns preferentially develop specific chemical synapses with each other rather than with nearby non-siblings. Although these findings provide crucial insight into the emergence of functional columns in the neocortex, little is known about the basis of this lineage-dependent assembly of excitatory neuron microcircuits at single-cell resolution. Here we show that transient electrical coupling between radially aligned sister excitatory neurons regulates the subsequent formation of specific chemical synapses in the neocortex. Multiple-electrode whole-cell recordings showed that sister excitatory neurons preferentially form strong electrical coupling with each other rather than with adjacent non-sister excitatory neurons during early postnatal stages. This preferential coupling allows selective electrical communication between sister excitatory neurons, promoting their action potential generation and synchronous firing. Interestingly, although this electrical communication largely disappears before the appearance of chemical synapses, blockade of the electrical communication impairs the subsequent formation of specific chemical synapses between sister excitatory neurons in ontogenetic columns. These results suggest a strong link between lineage-dependent transient electrical coupling and the assembly of precise excitatory neuron microcircuits in the neocortex.}, Author = {Yu, Yong-Chun and He, Shuijin and Chen, She and Fu, Yinghui and Brown, Keith N and Yao, Xing-Hua and Ma, Jian and Gao, Kate P and Sosinsky, Gina E and Huang, Kun and Shi, Song-Hai}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1038/nature10958}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Action Potentials; Animals; Animals, Newborn; Cell Lineage; Electric Conductivity; Electrical Synapses; Gap Junctions; Meclofenamic Acid; Mice; Models, Neurological; Neocortex; Neurons; Synaptic Transmission}, Month = {Jun}, Number = {7401}, Pages = {113-7}, Pmc = {PMC3599787}, pmid = {22678291}, Pst = {epublish}, Title = {Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly}, Volume = {486}, Year = {2012}, url = {papers/Yu_Nature2012.pdf}} @article{Rushmore:2006, Abstract = {Visuospatial neglect is a common neurological syndrome caused by unilateral brain damage to the posterior and inferior parietal cerebral cortex, and is characterized by an inability to respond or orient to stimuli presented in the contralesional hemifield. Neglect has been elicited in experimental models of the rat, cat and monkey, and is thought to result in part from a pathological state of inhibition exerted on the damaged hemisphere by the hyperexcited intact hemisphere. We sought to test this theory by assessing neural activity levels in multiple brain structures during neglect using 2-deoxyglucose (2DG) as a metabolic marker of neural activity. Neglect was induced in two ways: (i) by cooling deactivation of posterior parietal cortex or (ii) in conjunction with broader cortical blindness produced by unilateral lesion of all contiguous visual cortical areas spanning occipital, parietal and temporal regions. The direction and magnitude of changes in 2DG uptake were measured in cerebral cortex and midbrain structures. Finally, the 2DG uptake was assessed in a group of cats in which the lesion-induced neglect component of blindness was cancelled by cooling of either the contralateral posterior parietal cortex or the contralateral superior colliculus (SC). Overall, we found that (i) both lesion- and cooling-induced neglect are associated with decreases in 2DG uptake in specific ipsilateral cortical and midbrain regions; (ii) levels of 2DG uptake in the intermediate and deep layers of the SC contralateral to both cooling and lesion deactivations are increased; (iii) changes in 2DG uptake were not identified in the contralateral cortex; and (iv) reversal of the lesion-induced neglect component of blindness is associated with a reduction of contralesional 2DG uptake to normal or subnormal levels. These data are in accord with theories of neglect that include mutually suppressive mechanisms between the two hemispheres, and we show that these mechanisms operate at the level of the SC, but are not apparent at the level of cortex. These results suggest that the most effective therapies for visual neglect will be those that act to decrease neural activity in the intermediate layers of the SC contralateral to the brain damage.}, Author = {Rushmore, R Jarrett and Valero-Cabre, Antoni and Lomber, Stephen G and Hilgetag, Claus C and Payne, Bertram R}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1093/brain/awl140}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {downloads}, Mesh = {Animals; Blindness, Cortical; Brain Mapping; Cats; Cold Temperature; Deoxyglucose; Disease Models, Animal; Motion Perception; Parietal Lobe; Perceptual Disorders; Superior Colliculi; Visual Field Tests}, Month = {Jul}, Number = {Pt 7}, Pages = {1803-21}, pmid = {16731540}, Pst = {ppublish}, Title = {Functional circuitry underlying visual neglect}, Volume = {129}, Year = {2006}, url = {papers/Rushmore_Brain2006.pdf}} @article{Huster:2012, Abstract = {The simultaneous recording and analysis of electroencephalography (EEG) and fMRI data in human systems, cognitive and clinical neurosciences is rapidly evolving and has received substantial attention. The significance of multimodal brain imaging is documented by a steadily increasing number of laboratories now using simultaneous EEG-fMRI aiming to achieve both high temporal and spatial resolution of human brain function. Due to recent developments in technical and algorithmic instrumentation, the rate-limiting step in multimodal studies has shifted from data acquisition to analytic aspects. Here, we introduce and compare different methods for data integration and identify the benefits that come with each approach, guiding the reader toward an understanding and informed selection of the integration approach most suitable for addressing a particular research question.}, Author = {Huster, Ren{\'e} J and Debener, Stefan and Eichele, Tom and Herrmann, Christoph S}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1523/JNEUROSCI.0447-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Algorithms; Brain; Brain Mapping; Electroencephalography; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Subtraction Technique}, Month = {May}, Number = {18}, Pages = {6053-60}, pmid = {22553012}, Pst = {ppublish}, Title = {Methods for simultaneous EEG-fMRI: an introductory review}, Volume = {32}, Year = {2012}, url = {papers/Huster_JNeurosci2012.pdf}} @article{Min:2012, Abstract = {Endocannabinoid mediated spike timing-dependent depression (t-LTD) is crucially involved in the development of the sensory neocortex. t-LTD at excitatory synapses in the developing rat barrel cortex requires cannabinoid CB(1) receptor (CB(1)R) activation, as well as activation of NMDA receptors located on the presynaptic terminal, but the exact signaling cascade leading to t-LTD remains unclear. We found that astrocytes are critically involved in t-LTD. Astrocytes gradually increased their Ca(2+) signaling specifically during the induction of t-LTD in a CB(1)R-dependent manner. In this way, astrocytes might act as a memory buffer for previous coincident neuronal activity. Following activation, astrocytes released glutamate, which activated presynaptic NMDA receptors to induce t-LTD. Astrocyte stimulation coincident with afferent activity resulted in long-term depression, indicating that astrocyte activation is sufficient for the induction of synaptic depression. Taken together, our findings describe the retrograde signaling cascade underlying neocortical t-LTD. The critical involvement of astrocytes in this process highlights their importance for experience-dependent sensory remodeling.}, Author = {Min, Rogier and Nevian, Thomas}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1038/nn.3075}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {downloads}, Mesh = {2-Amino-5-phosphonovalerate; Animals; Animals, Newborn; Astrocytes; Benzoxazines; Biophysics; Calcium; Calcium Channel Blockers; Dizocilpine Maleate; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Glutamic Acid; Long-Term Synaptic Depression; Morpholines; Naphthalenes; Neocortex; Patch-Clamp Techniques; Piperidines; Probability; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Signal Transduction; Sodium Channel Blockers; Synapses; Tetrodotoxin; Thalamus; Time Factors}, Month = {May}, Number = {5}, Pages = {746-53}, pmid = {22446881}, Pst = {epublish}, Title = {Astrocyte signaling controls spike timing-dependent depression at neocortical synapses}, Volume = {15}, Year = {2012}, url = {papers/Min_NatNeurosci2012.pdf}} @article{Huber:2012, Abstract = {The mechanisms linking sensation and action during learning are poorly understood. Layer 2/3 neurons in the motor cortex might participate in sensorimotor integration and learning; they receive input from sensory cortex and excite deep layer neurons, which control movement. Here we imaged activity in the same set of layer 2/3 neurons in the motor cortex over weeks, while mice learned to detect objects with their whiskers and report detection with licking. Spatially intermingled neurons represented sensory (touch) and motor behaviours (whisker movements and licking). With learning, the population-level representation of task-related licking strengthened. In trained mice, population-level representations were redundant and stable, despite dynamism of single-neuron representations. The activity of a subpopulation of neurons was consistent with touch driving licking behaviour. Our results suggest that ensembles of motor cortex neurons couple sensory input to multiple, related motor programs during learning.}, Author = {Huber, D and Gutnisky, D A and Peron, S and O'Connor, D H and Wiegert, J S and Tian, L and Oertner, T G and Looger, L L and Svoboda, K}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1038/nature11039}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Behavior, Animal; Feedback, Sensory; Hippocampus; Learning; Long-Term Potentiation; Mice; Microscopy; Models, Neurological; Motor Cortex; Neuronal Plasticity; Psychomotor Performance; Rats; Tongue; Touch; Vibrissae}, Month = {Apr}, Number = {7395}, Pages = {473-8}, pmid = {22538608}, Pst = {epublish}, Title = {Multiple dynamic representations in the motor cortex during sensorimotor learning}, Volume = {484}, Year = {2012}, url = {papers/Huber_Nature2012.pdf}} @article{Madisen:2012, Abstract = {Cell type-specific expression of optogenetic molecules allows temporally precise manipulation of targeted neuronal activity. Here we present a toolbox of four knock-in mouse lines engineered for strong, Cre-dependent expression of channelrhodopsins ChR2-tdTomato and ChR2-EYFP, halorhodopsin eNpHR3.0 and archaerhodopsin Arch-ER2. All four transgenes mediated Cre-dependent, robust activation or silencing of cortical pyramidal neurons in vitro and in vivo upon light stimulation, with ChR2-EYFP and Arch-ER2 demonstrating light sensitivity approaching that of in utero or virally transduced neurons. We further show specific photoactivation of parvalbumin-positive interneurons in behaving ChR2-EYFP reporter mice. The robust, consistent and inducible nature of our ChR2 mice represents a significant advance over previous lines, and the Arch-ER2 and eNpHR3.0 mice are to our knowledge the first demonstration of successful conditional transgenic optogenetic silencing. When combined with the hundreds of available Cre driver lines, this optimized toolbox of reporter mice will enable widespread investigations of neural circuit function with unprecedented reliability and accuracy.}, Author = {Madisen, Linda and Mao, Tianyi and Koch, Henner and Zhuo, Jia-min and Berenyi, Antal and Fujisawa, Shigeyoshi and Hsu, Yun-Wei A and Garcia, 3rd, Alfredo J and Gu, Xuan and Zanella, Sebastien and Kidney, Jolene and Gu, Hong and Mao, Yimei and Hooks, Bryan M and Boyden, Edward S and Buzs{\'a}ki, Gy{\"o}rgy and Ramirez, Jan Marino and Jones, Allan R and Svoboda, Karel and Han, Xue and Turner, Eric E and Zeng, Hongkui}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1038/nn.3078}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {downloads}, Mesh = {Action Potentials; Animals; Archaeal Proteins; Brain; Electroporation; Halorhodopsins; Integrases; Light; Luminescent Proteins; Mice; Mice, Transgenic; Neurogenesis; Neurons; Optics and Photonics; Proteins; Rhodopsin; Wakefulness}, Month = {May}, Number = {5}, Pages = {793-802}, Pmc = {PMC3337962}, pmid = {22446880}, Pst = {epublish}, Title = {A toolbox of Cre-dependent optogenetic transgenic mice for light-induced activation and silencing}, Volume = {15}, Year = {2012}, url = {papers/Madisen_NatNeurosci2012.pdf}} @article{Wester:2012, Abstract = {The cortex is organized in vertical and horizontal circuits that determine the spatiotemporal properties of distributed cortical activity. Despite detailed knowledge of synaptic interactions among individual cells in the neocortex, little is known about the rules governing interactions among local populations. Here, we used self-sustained recurrent activity generated in cortex, also known as up-states, in rat thalamocortical slices in vitro to understand interactions among laminar and horizontal circuits. By means of intracellular recordings and fast optical imaging with voltage-sensitive dyes, we show that single thalamic inputs activate the cortical column in a preferential layer 4 (L4) → layer 2/3 (L2/3) → layer 5 (L5) sequence, followed by horizontal propagation with a leading front in supragranular and infragranular layers. To understand the laminar and columnar interactions, we used focal injections of TTX to block activity in small local populations, while preserving functional connectivity in the rest of the network. We show that L2/3 alone, without underlying L5, does not generate self-sustained activity and is inefficient propagating activity horizontally. In contrast, L5 sustains activity in the absence of L2/3 and is necessary and sufficient to propagate activity horizontally. However, loss of L2/3 delays horizontal propagation via L5. Finally, L5 amplifies activity in L2/3. Our results show for the first time that columnar interactions between supragranular and infragranular layers are required for the normal propagation of activity in the neocortex. Our data suggest that supragranular and infragranular circuits, with their specific and complex set of inputs and outputs, work in tandem to determine the patterns of cortical activation observed in vivo.}, Author = {Wester, Jason C and Contreras, Diego}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1523/JNEUROSCI.5006-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Electric Stimulation; Electron Transport Complex IV; Membrane Potentials; Neocortex; Nerve Net; Neural Pathways; Optics and Photonics; Rats; Rats, Sprague-Dawley; Recruitment, Neurophysiological; Sodium Channel Blockers; Tetrodotoxin; Thalamus; Voltage-Sensitive Dye Imaging}, Month = {Apr}, Number = {16}, Pages = {5454-71}, Pmc = {PMC3415278}, pmid = {22514308}, Pst = {ppublish}, Title = {Columnar interactions determine horizontal propagation of recurrent network activity in neocortex}, Volume = {32}, Year = {2012}, url = {papers/Wester_JNeurosci2012.pdf}} @article{Derecki:2012, Abstract = {Rett syndrome is an X-linked autism spectrum disorder. The disease is characterized in most cases by mutation of the MECP2 gene, which encodes a methyl-CpG-binding protein. Although MECP2 is expressed in many tissues, the disease is generally attributed to a primary neuronal dysfunction. However, as shown recently, glia, specifically astrocytes, also contribute to Rett pathophysiology. Here we examine the role of another form of glia, microglia, in a murine model of Rett syndrome. Transplantation of wild-type bone marrow into irradiation-conditioned Mecp2-null hosts resulted in engraftment of brain parenchyma by bone-marrow-derived myeloid cells of microglial phenotype, and arrest of disease development. However, when cranial irradiation was blocked by lead shield, and microglial engraftment was prevented, disease was not arrested. Similarly, targeted expression of MECP2 in myeloid cells, driven by Lysm(cre) on an Mecp2-null background, markedly attenuated disease symptoms. Thus, through multiple approaches, wild-type Mecp2-expressing microglia within the context of an Mecp2-null male mouse arrested numerous facets of disease pathology: lifespan was increased, breathing patterns were normalized, apnoeas were reduced, body weight was increased to near that of wild type, and locomotor activity was improved. Mecp2(+/-) females also showed significant improvements as a result of wild-type microglial engraftment. These benefits mediated by wild-type microglia, however, were diminished when phagocytic activity was inhibited pharmacologically by using annexin V to block phosphatydilserine residues on apoptotic targets, thus preventing recognition and engulfment by tissue-resident phagocytes. These results suggest the importance of microglial phagocytic activity in Rett syndrome. Our data implicate microglia as major players in the pathophysiology of this devastating disorder, and suggest that bone marrow transplantation might offer a feasible therapeutic approach for it.}, Author = {Derecki, No{\"e}l C and Cronk, James C and Lu, Zhenjie and Xu, Eric and Abbott, Stephen B G and Guyenet, Patrice G and Kipnis, Jonathan}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1038/nature10907}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Annexin A5; Apoptosis; Body Weight; Bone Marrow Transplantation; Brain; Disease Models, Animal; Disease Progression; Female; Insulin-Like Growth Factor I; Locomotion; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Inbred C57BL; Microglia; Phagocytosis; Phosphatidylserines; Respiration; Rett Syndrome; Rotarod Performance Test}, Month = {Apr}, Number = {7392}, Pages = {105-9}, Pmc = {PMC3321067}, pmid = {22425995}, Pst = {epublish}, Title = {Wild-type microglia arrest pathology in a mouse model of Rett syndrome}, Volume = {484}, Year = {2012}, url = {papers/Derecki_Nature2012.pdf}} @article{Simini:2012, Abstract = {Introduced in its contemporary form in 1946 (ref. 1), but with roots that go back to the eighteenth century, the gravity law is the prevailing framework with which to predict population movement, cargo shipping volume and inter-city phone calls, as well as bilateral trade flows between nations. Despite its widespread use, it relies on adjustable parameters that vary from region to region and suffers from known analytic inconsistencies. Here we introduce a stochastic process capturing local mobility decisions that helps us analytically derive commuting and mobility fluxes that require as input only information on the population distribution. The resulting radiation model predicts mobility patterns in good agreement with mobility and transport patterns observed in a wide range of phenomena, from long-term migration patterns to communication volume between different regions. Given its parameter-free nature, the model can be applied in areas where we lack previous mobility measurements, significantly improving the predictive accuracy of most of the phenomena affected by mobility and transport processes.}, Author = {Simini, Filippo and Gonz{\'a}lez, Marta C and Maritan, Amos and Barab{\'a}si, Albert-L{\'a}szl{\'o}}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2014-01-15 14:50:07 +0000}, Doi = {10.1038/nature10856}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {graph theory; Mathematics; models; self organization; network; Game Theory; Methods}, Mesh = {Emigration and Immigration; Europe; Internationality; Models, Statistical; Population Density; Population Dynamics; Statistical Distributions; Stochastic Processes; Telephone; Transportation; United States}, Month = {Apr}, Number = {7392}, Pages = {96-100}, pmid = {22367540}, Pst = {epublish}, Title = {A universal model for mobility and migration patterns}, Volume = {484}, Year = {2012}, url = {papers/Simini_Nature2012.pdf}} @article{Harvey:2012, Abstract = {The posterior parietal cortex (PPC) has an important role in many cognitive behaviours; however, the neural circuit dynamics underlying PPC function are not well understood. Here we optically imaged the spatial and temporal activity patterns of neuronal populations in mice performing a PPC-dependent task that combined a perceptual decision and memory-guided navigation in a virtual environment. Individual neurons had transient activation staggered relative to one another in time, forming a sequence of neuronal activation spanning the entire length of a task trial. Distinct sequences of neurons were triggered on trials with opposite behavioural choices and defined divergent, choice-specific trajectories through a state space of neuronal population activity. Cells participating in the different sequences and at distinct time points in the task were anatomically intermixed over microcircuit length scales (<100 micrometres). During working memory decision tasks, the PPC may therefore perform computations through sequence-based circuit dynamics, rather than long-lived stable states, implemented using anatomically intermingled microcircuits.}, Author = {Harvey, Christopher D and Coen, Philip and Tank, David W}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2014-09-15 21:57:26 +0000}, Doi = {10.1038/nature10918}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Posterior parietal cortex; ppc; Neocortex; Cerebral Cortex; mouse; in vivo; optical physiology; two-photon imaging; optical imaging; synchrony; Theoretical; Decision Making; memory; learning; Hippocampal; grid cells; Spatial Behavior; navigation; Attention}, Mesh = {Action Potentials; Animals; Decision Making; Male; Maze Learning; Memory; Mice; Mice, Inbred C57BL; Models, Neurological; Parietal Lobe; Photic Stimulation; User-Computer Interface}, Month = {Apr}, Number = {7392}, Pages = {62-8}, Pmc = {PMC3321074}, pmid = {22419153}, Pst = {epublish}, Title = {Choice-specific sequences in parietal cortex during a virtual-navigation decision task}, Volume = {484}, Year = {2012}, url = {papers/Harvey_Nature2012.pdf}, Bdsk-File-2 = {papers/Harvey_Nature2012a.pdf}} @article{Petersen:2004b, Abstract = {The functional and anatomical rearrangements of cortical sensory maps accompanying changes in experience are not well understood. We examined in vivo and in vitro how the sensory map and underlying synaptic connectivity of the developing rat barrel cortex are altered when the sensory input to the cortex is partially deprived. In the nondeprived cortex, both the sensory responses and synaptic connectivity between columns were strengthened through an increase in the synaptic connection probability between L2/3 pyramids in adjacent columns. This was accompanied by a selective growth of L2/3pyramid axonal arbors between spared columns. In contrast, deprived and nondeprived cortical columns became weakly connected in their L2/3 pyramid connections.}, Author = {Petersen, Carl C H and Brecht, Michael and Hahn, Thomas T G and Sakmann, Bert}, Date-Added = {2013-04-01 16:16:30 +0000}, Date-Modified = {2013-04-01 16:17:05 +0000}, Doi = {10.1126/science.1096750}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {downloads}, Mesh = {Action Potentials; Animals; Brain Mapping; Electric Stimulation; Excitatory Postsynaptic Potentials; Image Processing, Computer-Assisted; Nerve Net; Neuronal Plasticity; Patch-Clamp Techniques; Pyramidal Cells; Rats; Rats, Wistar; Somatosensory Cortex; Synapses; Synaptic Transmission; Vibrissae}, Month = {Apr}, Number = {5671}, Pages = {739-42}, pmid = {15118164}, Pst = {ppublish}, Title = {Synaptic changes in layer 2/3 underlying map plasticity of developing barrel cortex}, Volume = {304}, Year = {2004}, url = {papers/Petersen_Science2004.pdf}} @article{Lee:2012, Abstract = {Inhibitory interneurons are essential components of the neural circuits underlying various brain functions. In the neocortex, a large diversity of GABA (γ-aminobutyric acid) interneurons has been identified on the basis of their morphology, molecular markers, biophysical properties and innervation pattern. However, how the activity of each subtype of interneurons contributes to sensory processing remains unclear. Here we show that optogenetic activation of parvalbumin-positive (PV+) interneurons in the mouse primary visual cortex (V1) sharpens neuronal feature selectivity and improves perceptual discrimination. Using multichannel recording with silicon probes and channelrhodopsin-2 (ChR2)-mediated optical activation, we found that increased spiking of PV+ interneurons markedly sharpened orientation tuning and enhanced direction selectivity of nearby neurons. These effects were caused by the activation of inhibitory neurons rather than a decreased spiking of excitatory neurons, as archaerhodopsin-3 (Arch)-mediated optical silencing of calcium/calmodulin-dependent protein kinase IIα (CAMKIIα)-positive excitatory neurons caused no significant change in V1 stimulus selectivity. Moreover, the improved selectivity specifically required PV+ neuron activation, as activating somatostatin or vasointestinal peptide interneurons had no significant effect. Notably, PV+ neuron activation in awake mice caused a significant improvement in their orientation discrimination, mirroring the sharpened V1 orientation tuning. Together, these results provide the first demonstration that visual coding and perception can be improved by increased spiking of a specific subtype of cortical inhibitory interneurons.}, Author = {Lee, Seung-Hee and Kwan, Alex C and Zhang, Siyu and Phoumthipphavong, Victoria and Flannery, John G and Masmanidis, Sotiris C and Taniguchi, Hiroki and Huang, Z Josh and Zhang, Feng and Boyden, Edward S and Deisseroth, Karl and Dan, Yang}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.1038/nature11312}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Discrimination Learning; Interneurons; Mice; Models, Neurological; Neural Inhibition; Parvalbumins; Rhodopsin; Rhodopsins, Microbial; Visual Cortex; Visual Perception; Wakefulness; gamma-Aminobutyric Acid}, Month = {Aug}, Number = {7411}, Pages = {379-83}, Pmc = {PMC3422431}, pmid = {22878719}, Pst = {ppublish}, Title = {Activation of specific interneurons improves V1 feature selectivity and visual perception}, Volume = {488}, Year = {2012}, url = {papers/Lee_Nature2012.pdf}} @article{Wilson:2012, Abstract = {Brain circuits process information through specialized neuronal subclasses interacting within a network. Revealing their interplay requires activating specific cells while monitoring others in a functioning circuit. Here we use a new platform for two-way light-based circuit interrogation in visual cortex in vivo to show the computational implications of modulating different subclasses of inhibitory neurons during sensory processing. We find that soma-targeting, parvalbumin-expressing (PV) neurons principally divide responses but preserve stimulus selectivity, whereas dendrite-targeting, somatostatin-expressing (SOM) neurons principally subtract from excitatory responses and sharpen selectivity. Visualized in vivo cell-attached recordings show that division by PV neurons alters response gain, whereas subtraction by SOM neurons shifts response levels. Finally, stimulating identified neurons while scanning many target cells reveals that single PV and SOM neurons functionally impact only specific subsets of neurons in their projection fields. These findings provide direct evidence that inhibitory neuronal subclasses have distinct and complementary roles in cortical computations.}, Author = {Wilson, Nathan R and Runyan, Caroline A and Wang, Forea L and Sur, Mriganka}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.1038/nature11347}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Dendrites; Electrophysiology; Interneurons; Mice; Models, Neurological; Neural Inhibition; Neural Pathways; Neurons; Parvalbumins; Somatostatin; Visual Cortex}, Month = {Aug}, Number = {7411}, Pages = {343-8}, pmid = {22878717}, Pst = {ppublish}, Title = {Division and subtraction by distinct cortical inhibitory networks in vivo}, Volume = {488}, Year = {2012}, url = {papers/Wilson_Nature2012.pdf}} @article{West:2011, Abstract = {Activity-dependent plasticity of vertebrate neurons allows the brain to respond to its environment. During brain development, both spontaneous and sensory-driven neural activity are essential for instructively guiding the process of synapse development. These effects of neuronal activity are transduced in part through the concerted regulation of a set of activity-dependent transcription factors that coordinate a program of gene expression required for the formation and maturation of synapses. Here we review the cellular signaling networks that regulate the activity of transcription factors during brain development and discuss the functional roles of specific activity-regulated transcription factors in specific stages of synapse formation, refinement, and maturation. Interestingly, a number of neurodevelopmental disorders have been linked to abnormalities in activity-regulated transcriptional pathways, indicating that these signaling networks are critical for cognitive development and function.}, Author = {West, Anne E and Greenberg, Michael E}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.1101/cshperspect.a005744}, Journal = {Cold Spring Harb Perspect Biol}, Journal-Full = {Cold Spring Harbor perspectives in biology}, Keywords = {downloads}, Mesh = {Calcium Signaling; Cognition Disorders; Gene Expression Regulation; Humans; Models, Genetic; Neurites; Neuronal Plasticity; Neurons; Synapses; Synaptic Transmission; Transcription Factors}, Month = {Jun}, Number = {6}, Pmc = {PMC3098681}, pmid = {21555405}, Pst = {epublish}, Title = {Neuronal activity-regulated gene transcription in synapse development and cognitive function}, Volume = {3}, Year = {2011}, url = {papers/West_ColdSpringHarbPerspectBiol2011.pdf}} @article{Petrof:2012, Abstract = {The subgranular layers (layers 5 and 6) of primary sensory cortex provide corticofugal output to thalamus and they also project to the appropriate secondary sensory cortices. Here we injected two combinations of different color retrograde fluorescent markers in the thalamic and cortical targets of these layers from the three primary sensory cortices (somatosensory, auditory, and visual) in mice to examine the degree of overlap between corticothalamic and interareal corticocortical cells in the subgranular layers. We found that, for all three primary sensory cortices, double-labeled cells were extremely rare, indicating that corticothalamic and interareal corticocortical cells in the subgranular layers represent largely independent populations.}, Author = {Petrof, Iraklis and Viaene, Angela N and Sherman, S Murray}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.1002/cne.23006}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {downloads}, Mesh = {Animals; Cell Count; Fluorescent Dyes; Immunohistochemistry; Mice; Mice, Inbred BALB C; Neurons; Somatosensory Cortex}, Month = {Jun}, Number = {8}, Pages = {1678-86}, Pmc = {PMC3561675}, pmid = {22120996}, Pst = {ppublish}, Title = {Two populations of corticothalamic and interareal corticocortical cells in the subgranular layers of the mouse primary sensory cortices}, Volume = {520}, Year = {2012}, url = {papers/Petrof_JCompNeurol2012.pdf}} @article{Nassi:2009, Abstract = {Incoming sensory information is sent to the brain along modality-specific channels corresponding to the five senses. Each of these channels further parses the incoming signals into parallel streams to provide a compact, efficient input to the brain. Ultimately, these parallel input signals must be elaborated on and integrated in the cortex to provide a unified and coherent percept. Recent studies in the primate visual cortex have greatly contributed to our understanding of how this goal is accomplished. Multiple strategies including retinal tiling, hierarchical and parallel processing and modularity, defined spatially and by cell type-specific connectivity, are used by the visual system to recover the intricate detail of our visual surroundings.}, Author = {Nassi, Jonathan J and Callaway, Edward M}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.1038/nrn2619}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Humans; Models, Biological; Primates; Retina; Sensory Receptor Cells; Vision, Ocular; Visual Cortex; Visual Pathways; Visual Perception}, Month = {May}, Number = {5}, Pages = {360-72}, Pmc = {PMC2771435}, pmid = {19352403}, Pst = {ppublish}, Title = {Parallel processing strategies of the primate visual system}, Volume = {10}, Year = {2009}, url = {papers/Nassi_NatRevNeurosci2009.pdf}} @article{Yu:2012, Abstract = {In primates, prostriata is a small area located between the primary visual cortex (V1) and the hippocampal formation. Prostriata sends connections to multisensory and high-order association areas in the temporal, parietal, cingulate, orbitofrontal, and frontopolar cortices. It is characterized by a relatively simple histological organization, alluding to an early origin in mammalian evolution. Here we show that prostriata neurons in marmoset monkeys exhibit a unique combination of response properties, suggesting a new pathway for rapid distribution of visual information in parallel with the traditionally recognized dorsal and ventral streams. Whereas the location and known connections of prostriata suggest a high-level association area, its response properties are unexpectedly simple, resembling those found in early stages of the visual processing: neurons have robust, nonadapting responses to simple stimuli, with latencies comparable to those found in V1, and are broadly tuned to stimulus orientation and spatiotemporal frequency. However, their receptive fields are enormous and form a unique topographic map that emphasizes the far periphery of the visual field. These results suggest a specialized circuit through which stimuli in peripheral vision can bypass the elaborate hierarchy of extrastriate visual areas and rapidly elicit coordinated motor and cognitive responses across multiple brain systems.}, Author = {Yu, Hsin-Hao and Chaplin, Tristan A and Davies, Amanda J and Verma, Richa and Rosa, Marcello G P}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.1016/j.cub.2012.05.029}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {downloads}, Mesh = {Animals; Brain Mapping; Callitrichinae; Limbic System; Visual Pathways; Visual Perception}, Month = {Jul}, Number = {14}, Pages = {1351-7}, pmid = {22704993}, Pst = {ppublish}, Title = {A specialized area in limbic cortex for fast analysis of peripheral vision}, Volume = {22}, Year = {2012}, url = {papers/Yu_CurrBiol2012.pdf}} @article{Paul:2012, Abstract = {The assembly of neural circuits involves multiple sequential steps such as the specification of cell-types, their migration to proper brain locations, morphological and physiological differentiation, and the formation and maturation of synaptic connections. This intricate and often prolonged process is guided by elaborate genetic mechanisms that regulate each step. Evidence from numerous systems suggests that each cell-type, once specified, is endowed with a genetic program that unfolds in response to, and is regulated by, extrinsic signals, including cell-cell and synaptic interactions. To a large extent, the execution of this intrinsic program is achieved by the expression of specific sets of genes that support distinct developmental processes. Therefore, a comprehensive analysis of the developmental progression of gene expression in synaptic partners of neurons may provide a basis for exploring the genetic mechanisms regulating circuit assembly. Here we examined the developmental gene expression profiles of well-defined cell-types in a stereotyped microcircuit of the cerebellar cortex. We found that the transcriptomes of Purkinje cell and stellate/basket cells are highly dynamic throughout postnatal development. We revealed "phasic expression" of transcription factors, ion channels, receptors, cell adhesion molecules, gap junction proteins, and identified distinct molecular pathways that might contribute to sequential steps of cerebellar inhibitory circuit formation. We further revealed a correlation between genomic clustering and developmental co-expression of hundreds of transcripts, suggesting the involvement of chromatin level gene regulation during circuit formation.}, Author = {Paul, Anirban and Cai, Ying and Atwal, Gurinder S and Huang, Z Josh}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.3389/fncir.2012.00037}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {downloads}, Pages = {37}, Pmc = {PMC3385560}, pmid = {22754500}, Pst = {ppublish}, Title = {Developmental Coordination of Gene Expression between Synaptic Partners During GABAergic Circuit Assembly in Cerebellar Cortex}, Volume = {6}, Year = {2012}, url = {papers/Paul_FrontNeuralCircuits2012.pdf}} @article{Thomson:2010, Abstract = {This review attempts to summarise some of the major areas of neocortical research as it pertains to neocortical layer 6. After a brief summary of the development of this intriguing layer, the major pyramidal cell classes to be found in layer 6 are described and compared. The connections made and received by these different classes of neurones are then discussed and the possible functions of these connections, with particular reference to the shaping of responses in visual cortex and thalamus. Inhibition in layer 6 is discussed where appropriate, but not in great detail. Many types of interneurones are to be found in each cortical layer and layer 6 is no exception, but the functions of each type remain to be elucidated (Gonchar et al., 2007).}, Author = {Thomson, Alex M}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.3389/fnana.2010.00013}, Journal = {Front Neuroanat}, Journal-Full = {Frontiers in neuroanatomy}, Keywords = {downloads}, Pages = {13}, Pmc = {PMC2885865}, pmid = {20556241}, Pst = {epublish}, Title = {Neocortical layer 6, a review}, Volume = {4}, Year = {2010}, url = {papers/Thomson_FrontNeuroanat2010.pdf}} @article{Mahou:2012, Abstract = {We achieve simultaneous two-photon excitation of three chromophores with distinct absorption spectra using synchronized pulses from a femtosecond laser and an optical parametric oscillator. The two beams generate separate multiphoton processes, and their spatiotemporal overlap provides an additional two-photon excitation route, with submicrometer overlay of the color channels. We report volume and live multicolor imaging of 'Brainbow'-labeled tissues as well as simultaneous three-color fluorescence and third-harmonic imaging of fly embryos.}, Author = {Mahou, Pierre and Zimmerley, Maxwell and Loulier, Karine and Matho, Katherine S and Labroille, Guillaume and Morin, Xavier and Supatto, Willy and Livet, Jean and D{\'e}barre, Delphine and Beaurepaire, Emmanuel}, Date-Added = {2013-04-01 16:14:10 +0000}, Date-Modified = {2013-04-01 16:15:03 +0000}, Doi = {10.1038/nmeth.2098}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {downloads}, Mesh = {Animals; Cerebral Cortex; Color; Drosophila melanogaster; Fluorescence; Lasers; Mice; Microscopy, Fluorescence, Multiphoton; Photons; Time Factors}, Month = {Aug}, Number = {8}, Pages = {815-8}, pmid = {22772730}, Pst = {epublish}, Title = {Multicolor two-photon tissue imaging by wavelength mixing}, Volume = {9}, Year = {2012}, url = {papers/Mahou_NatMethods2012.pdf}} @article{Clemens:2012, Abstract = {Sensory experience plays a critical role in the development of cortical circuits. At the time of eye opening, visual cortical neurons in the ferret exhibit orientation selectivity, but lack direction selectivity, which is a feature of mature cortical neurons in this species. Direction selectivity emerges in the days and weeks following eye opening via a process that requires visual experience. However, the circuit mechanisms that underlie the development of direction selectivity remain unclear. Here, we used microelectrodes to examine the laminar chronology of the development of direction selectivity around the time of eye opening to identify the locations within the cortical circuit that are altered during this process. We found that neurons in layers 4 and 2/3 exhibited weak direction selectivity just before natural eye opening. Layer 4 neurons in animals that had opened their eyes but were younger than postnatal day 35 (PND 35) exhibited modestly increased direction selectivity, but layer 2/3 cells remained as weakly tuned as before eye opening. Animals that had opened their eyes and were PND 35 or older exhibited increased direction selectivity in both layers 4 and 2/3. On average, initial increases in direction selectivity in animals younger than PND 35 were explained by increases in responses to the preferred direction, while subsequent increases in direction selectivity in animals PND 35 or older were explained by decreases in responses to the null direction. These results suggest that all cortical layers are influenced by sensory stimulation during early stages of experience-dependent development.}, Author = {Clemens, Jared M and Ritter, Neil J and Roy, Arani and Miller, Julie M and Van Hooser, Stephen D}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.3399-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Female; Ferrets; Immunohistochemistry; Male; Microelectrodes; Neurons; Orientation; Photic Stimulation; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Dec}, Number = {50}, Pages = {18177-85}, Pmc = {PMC3532899}, pmid = {23238731}, Pst = {ppublish}, Title = {The laminar development of direction selectivity in ferret visual cortex}, Volume = {32}, Year = {2012}, url = {papers/Clemens_JNeurosci2012.pdf}} @article{Stensola:2012, Abstract = {The medial entorhinal cortex (MEC) is part of the brain's circuit for dynamic representation of self-location. The metric of this representation is provided by grid cells, cells with spatial firing fields that tile environments in a periodic hexagonal pattern. Limited anatomical sampling has obscured whether the grid system operates as a unified system or a conglomerate of independent modules. Here we show with recordings from up to 186 grid cells in individual rats that grid cells cluster into a small number of layer-spanning anatomically overlapping modules with distinct scale, orientation, asymmetry and theta-frequency modulation. These modules can respond independently to changes in the geometry of the environment. The discrete topography of the grid-map, and the apparent autonomy of the modules, differ from the graded topography of maps for continuous variables in several sensory systems, raising the possibility that the modularity of the grid map is a product of local self-organizing network dynamics.}, Author = {Stensola, Hanne and Stensola, Tor and Solstad, Trygve and Fr{\o}land, Kristian and Moser, May-Britt and Moser, Edvard I}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2014-09-16 14:36:50 +0000}, Doi = {10.1038/nature11649}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {rat; grid cells; hippocampus; Spatial Behavior; navigation; Entorhinal Cortex;}, Mesh = {Animals; Entorhinal Cortex; Environment; Male; Models, Neurological; Orientation; Rats; Rats, Long-Evans; Theta Rhythm}, Month = {Dec}, Number = {7427}, Pages = {72-8}, pmid = {23222610}, Pst = {ppublish}, Title = {The entorhinal grid map is discretized}, Volume = {492}, Year = {2012}, url = {papers/Stensola_Nature2012.pdf}} @article{Su:2012, Abstract = {Diverse sensory organs, including mammalian taste buds and insect chemosensory sensilla, show a marked compartmentalization of receptor cells; however, the functional impact of this organization remains unclear. Here we show that compartmentalized Drosophila olfactory receptor neurons (ORNs) communicate with each other directly. The sustained response of one ORN is inhibited by the transient activation of a neighbouring ORN. Mechanistically, such lateral inhibition does not depend on synapses and is probably mediated by ephaptic coupling. Moreover, lateral inhibition in the periphery can modulate olfactory behaviour. Together, the results show that integration of olfactory information can occur via lateral interactions between ORNs. Inhibition of a sustained response by a transient response may provide a means of encoding salience. Finally, a CO(2)-sensitive ORN in the malaria mosquito Anopheles can also be inhibited by excitation of an adjacent ORN, suggesting a broad occurrence of lateral inhibition in insects and possible applications in insect control.}, Author = {Su, Chih-Ying and Menuz, Karen and Reisert, Johannes and Carlson, John R}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1038/nature11712}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Anopheles gambiae; Carbon Dioxide; Dose-Response Relationship, Drug; Drosophila melanogaster; Female; Neural Inhibition; Olfactory Pathways; Olfactory Receptor Neurons; Sensilla; Smell; Synapses; Synaptic Transmission}, Month = {Dec}, Number = {7427}, Pages = {66-71}, Pmc = {PMC3518700}, pmid = {23172146}, Pst = {ppublish}, Title = {Non-synaptic inhibition between grouped neurons in an olfactory circuit}, Volume = {492}, Year = {2012}, url = {papers/Su_Nature2012.pdf}} @article{Yang:2010a, Abstract = {Imaging neurons, glia and vasculature in the living brain has become an important experimental tool for understanding how the brain works. Here we describe in detail a protocol for imaging cortical structures at high optical resolution through a thinned-skull cranial window in live mice using two-photon laser scanning microscopy (TPLSM). Surgery can be performed within 30-45 min and images can be acquired immediately thereafter. The procedure can be repeated multiple times allowing longitudinal imaging of the cortex over intervals ranging from days to years. Imaging through a thinned-skull cranial window avoids exposure of the meninges and the cortex, thus providing a minimally invasive approach for studying structural and functional changes of cells under normal and pathological conditions in the living brain.}, Author = {Yang, Guang and Pan, Feng and Parkhurst, Christopher N and Grutzendler, Jaime and Gan, Wen-Biao}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1038/nprot.2009.222}, Journal = {Nat Protoc}, Journal-Full = {Nature protocols}, Keywords = {downloads}, Mesh = {Animals; Axons; Cerebral Cortex; Dendrites; Equipment Design; Indicators and Reagents; Luminescent Proteins; Mice; Mice, Transgenic; Microscopy, Confocal; Neurons; Photons; Skull; Synapses}, Month = {Feb}, Number = {2}, Pages = {201-8}, pmid = {20134419}, Pst = {ppublish}, Title = {Thinned-skull cranial window technique for long-term imaging of the cortex in live mice}, Volume = {5}, Year = {2010}, url = {papers/Yang_NatProtoc2010a.pdf}} @article{Warner:2012, Abstract = {The hierarchical development of the primate visual cortex and associated streams remains somewhat of a mystery. While anatomical, physiological, and psychological studies have demonstrated the early maturation of the dorsal "where"/"how" or motion cortical stream, little is known about the circuitry responsible. The influence of the retinogeniculostriate pathway has been investigated, but little attention has been paid to the role of two more recently described disynaptic retinothalamic projections to the middle temporal (MT) area, an early maturing dorsal stream cortical field, and which bypass the primary visual cortex (V1). These pathways are via the koniocellular layers of the lateral geniculate nucleus (LGN) and the medial portion of the inferior pulvinar (PIm). Both have been demonstrated in the adult nonhuman primate, but their influence during the maturation of the visual cortex is unknown. We used a combination of neural tracing and immunohistochemistry to follow the development of LGN and PIm inputs to area MT in the marmoset monkey. Our results revealed that the early maturation of area MT is likely due to the disynaptic retinopulvinar input and not the retinogeniculate input or the direct projection from V1. Furthermore, from soon after birth to adulthood, there was a dynamic shift in the ratio of input from these three structures to area MT, with an increasing dominance of the direct V1 afference.}, Author = {Warner, Claire E and Kwan, William C and Bourne, James A}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.3269-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Callithrix; Female; Geniculate Bodies; Male; Neurons; Pulvinar; Visual Cortex; Visual Pathways}, Month = {Nov}, Number = {48}, Pages = {17073-85}, pmid = {23197701}, Pst = {ppublish}, Title = {The early maturation of visual cortical area MT is dependent on input from the retinorecipient medial portion of the inferior pulvinar}, Volume = {32}, Year = {2012}, url = {papers/Warner_JNeurosci2012.pdf}} @article{Okun:2012, Abstract = {Cortical circuits encode sensory stimuli through the firing of neuronal ensembles, and also produce spontaneous population patterns in the absence of sensory drive. This population activity is often characterized experimentally by the distribution of multineuron "words" (binary firing vectors), and a match between spontaneous and evoked word distributions has been suggested to reflect learning of a probabilistic model of the sensory world. We analyzed multineuron word distributions in sensory cortex of anesthetized rats and cats, and found that they are dominated by fluctuations in population firing rate rather than precise interactions between individual units. Furthermore, cortical word distributions change when brain state shifts, and similar behavior is seen in simulated networks with fixed, random connectivity. Our results suggest that similarity or dissimilarity in multineuron word distributions could primarily reflect similarity or dissimilarity in population firing rate dynamics, and not necessarily the precise interactions between neurons that would indicate learning of sensory features.}, Author = {Okun, Michael and Yger, Pierre and Marguet, Stephan L and Gerard-Mercier, Florian and Benucci, Andrea and Katzner, Steffen and Busse, Laura and Carandini, Matteo and Harris, Kenneth D}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.1831-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Action Potentials; Animals; Cats; Male; Models, Neurological; Nerve Net; Neurons; Rats; Rats, Sprague-Dawley; Somatosensory Cortex}, Month = {Nov}, Number = {48}, Pages = {17108-19}, Pmc = {PMC3520056}, pmid = {23197704}, Pst = {ppublish}, Title = {Population rate dynamics and multineuron firing patterns in sensory cortex}, Volume = {32}, Year = {2012}, url = {papers/Okun_JNeurosci2012.pdf}} @article{Mancini:2012, Abstract = {Topographic maps of the receptive surface are a fundamental feature of neural organization in many sensory systems. While touch is finely mapped in the cerebral cortex, it remains controversial how precise any cortical nociceptive map may be. Given that nociceptive innervation density is relatively low on distal skin regions such as the digits, one might conclude that the nociceptive system lacks fine representation of these regions. Indeed, only gross spatial organization of nociceptive maps has been reported so far. However, here we reveal the existence of fine-grained somatotopy for nociceptive inputs to the digits in human primary somatosensory cortex (SI). Using painful nociceptive-selective laser stimuli to the hand, and phase-encoded functional magnetic resonance imaging analysis methods, we observed somatotopic maps of the digits in contralateral SI. These nociceptive maps were highly aligned with maps of non-painful tactile stimuli, suggesting comparable cortical representations for, and possible interactions between, mechanoreceptive and nociceptive signals. Our findings may also be valuable for future studies tracking the time course and the spatial pattern of plastic changes in cortical organization involved in chronic pain.}, Author = {Mancini, Flavia and Haggard, Patrick and Iannetti, Gian Domenico and Longo, Matthew R and Sereno, Martin I}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.3059-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Brain Mapping; Female; Hand; Humans; Magnetic Resonance Imaging; Male; Nociception; Pain; Physical Stimulation; Skin; Somatosensory Cortex}, Month = {Nov}, Number = {48}, Pages = {17155-62}, Pmc = {PMC3529201}, pmid = {23197708}, Pst = {ppublish}, Title = {Fine-grained nociceptive maps in primary somatosensory cortex}, Volume = {32}, Year = {2012}, url = {papers/Mancini_JNeurosci2012.pdf}} @article{Ren:2012, Abstract = {Rett syndrome (RTT) is a severe neurological disorder that is associated with mutations in the methyl-CpG binding protein 2 (MECP2) gene. RTT patients suffer from mental retardation and behavioral disorders, including heightened anxiety and state-dependent breathing irregularities, such as hyperventilation and apnea. Many symptoms are recapitulated by the Mecp2-null male mice (Mecp2(-/y)). To characterize developmental progression of the respiratory phenotype and explore underlying mechanisms, we examined Mecp2(-/y) and wild-type (WT) mice from presymptomatic periods to end-stage disease. We monitored breathing patterns of unrestrained mice during wake-sleep states and while altering stress levels using movement restraint or threatening odorant (trimethylthiazoline). Respiratory motor patterns generated by in situ working heart-brainstem preparations (WHBPs) were measured to assess function of brainstem respiratory networks isolated from suprapontine structures. Data revealed two general stages of respiratory dysfunction in Mecp2(-/y) mice. At the early stage, respiratory abnormalities were limited to wakefulness, correlated with markers of stress (increased fecal deposition and blood corticosterone levels), and alleviated by antalarmin (corticotropin releasing hormone receptor 1 antagonist). Furthermore, the respiratory rhythm generated by WHBPs was similar in WT and Mecp2(-/y) mice. During the later stage, respiratory abnormalities were evident during wakefulness and sleep. Also, WHBPs from Mecp2(-/y) showed central apneas. We conclude that, at early disease stages, stress-related modulation from suprapontine structures is a significant factor in the Mecp2(-/y) respiratory phenotype and that anxiolytics may be effective. At later stages, abnormalities of brainstem respiratory networks are a significant cause of irregular breathing patterns and central apneas.}, Author = {Ren, Jun and Ding, Xiuqing and Funk, Gregory D and Greer, John J}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.2951-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Anxiety; Disease Models, Animal; Male; Methyl-CpG-Binding Protein 2; Mice; Respiration; Respiration Disorders; Rett Syndrome; Wakefulness}, Month = {Nov}, Number = {48}, Pages = {17230-40}, pmid = {23197715}, Pst = {ppublish}, Title = {Anxiety-related mechanisms of respiratory dysfunction in a mouse model of Rett syndrome}, Volume = {32}, Year = {2012}, url = {papers/Ren_JNeurosci2012.pdf}} @article{Stevenson:2012, Abstract = {How interactions between neurons relate to tuned neural responses is a longstanding question in systems neuroscience. Here we use statistical modeling and simultaneous multi-electrode recordings to explore the relationship between these interactions and tuning curves in six different brain areas. We find that, in most cases, functional interactions between neurons provide an explanation of spiking that complements and, in some cases, surpasses the influence of canonical tuning curves. Modeling functional interactions improves both encoding and decoding accuracy by accounting for noise correlations and features of the external world that tuning curves fail to capture. In cortex, modeling coupling alone allows spikes to be predicted more accurately than tuning curve models based on external variables. These results suggest that statistical models of functional interactions between even relatively small numbers of neurons may provide a useful framework for examining neural coding.}, Author = {Stevenson, Ian H and London, Brian M and Oby, Emily R and Sachs, Nicholas A and Reimer, Jacob and Englitz, Bernhard and David, Stephen V and Shamma, Shihab A and Blanche, Timothy J and Mizuseki, Kenji and Zandvakili, Amin and Hatsopoulos, Nicholas G and Miller, Lee E and Kording, Konrad P}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1371/journal.pcbi.1002775}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {downloads}, Number = {11}, Pages = {e1002775}, Pmc = {PMC3499254}, pmid = {23166484}, Pst = {ppublish}, Title = {Functional connectivity and tuning curves in populations of simultaneously recorded neurons}, Volume = {8}, Year = {2012}, url = {papers/Stevenson_PLoSComputBiol2012.pdf}} @article{Reichl:2012, Abstract = {In the juvenile brain, the synaptic architecture of the visual cortex remains in a state of flux for months after the natural onset of vision and the initial emergence of feature selectivity in visual cortical neurons. It is an attractive hypothesis that visual cortical architecture is shaped during this extended period of juvenile plasticity by the coordinated optimization of multiple visual cortical maps such as orientation preference (OP), ocular dominance (OD), spatial frequency, or direction preference. In part (I) of this study we introduced a class of analytically tractable coordinated optimization models and solved representative examples, in which a spatially complex organization of the OP map is induced by interactions between the maps. We found that these solutions near symmetry breaking threshold predict a highly ordered map layout. Here we examine the time course of the convergence towards attractor states and optima of these models. In particular, we determine the timescales on which map optimization takes place and how these timescales can be compared to those of visual cortical development and plasticity. We also assess whether our models exhibit biologically more realistic, spatially irregular solutions at a finite distance from threshold, when the spatial periodicities of the two maps are detuned and when considering more than 2 feature dimensions. We show that, although maps typically undergo substantial rearrangement, no other solutions than pinwheel crystals and stripes dominate in the emerging layouts. Pinwheel crystallization takes place on a rather short timescale and can also occur for detuned wavelengths of different maps. Our numerical results thus support the view that neither minimal energy states nor intermediate transient states of our coordinated optimization models successfully explain the architecture of the visual cortex. We discuss several alternative scenarios that may improve the agreement between model solutions and biological observations.}, Author = {Reichl, Lars and Heide, Dominik and L{\"o}wel, Siegrid and Crowley, Justin C and Kaschube, Matthias and Wolf, Fred}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1371/journal.pcbi.1002756}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {downloads}, Number = {11}, Pages = {e1002756}, Pmc = {PMC3493502}, pmid = {23144602}, Pst = {ppublish}, Title = {Coordinated optimization of visual cortical maps (II) numerical studies}, Volume = {8}, Year = {2012}, url = {papers/Reichl_PLoSComputBiol2012.pdf}} @article{Mukamel:2010a, Abstract = {Direct recordings in monkeys have demonstrated that neurons in frontal and parietal areas discharge during execution and perception of actions [1-8]. Because these discharges "reflect" the perceptual aspects of actions of others onto the motor repertoire of the perceiver, these cells have been called mirror neurons. Their overlapping sensory-motor representations have been implicated in observational learning and imitation, two important forms of learning [9]. In humans, indirect measures of neural activity support the existence of sensory-motor mirroring mechanisms in homolog frontal and parietal areas [10, 11], other motor regions [12-15], and also the existence of multisensory mirroring mechanisms in nonmotor regions [16-19]. We recorded extracellular activity from 1177 cells in human medial frontal and temporal cortices while patients executed or observed hand grasping actions and facial emotional expressions. A significant proportion of neurons in supplementary motor area, and hippocampus and environs, responded to both observation and execution of these actions. A subset of these neurons demonstrated excitation during action-execution and inhibition during action-observation. These findings suggest that multiple systems in humans may be endowed with neural mechanisms of mirroring for both the integration and differentiation of perceptual and motor aspects of actions performed by self and others.}, Author = {Mukamel, Roy and Ekstrom, Arne D and Kaplan, Jonas and Iacoboni, Marco and Fried, Itzhak}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1016/j.cub.2010.02.045}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {downloads}, Mesh = {Animals; Cerebral Cortex; Electrophysiology; Emotions; Facial Expression; Hand; Humans; Imitative Behavior; Motor Activity; Neurons; Psychomotor Performance; Visual Perception}, Month = {Apr}, Number = {8}, Pages = {750-6}, Pmc = {PMC2904852}, pmid = {20381353}, Pst = {ppublish}, Title = {Single-neuron responses in humans during execution and observation of actions}, Volume = {20}, Year = {2010}, url = {papers/Mukamel_CurrBiol2010a.pdf}} @article{Sato:2012b, Abstract = {The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening by in situ hybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner.}, Author = {Sato, Haruka and Fukutani, Yuma and Yamamoto, Yuji and Tatara, Eiichi and Takemoto, Makoto and Shimamura, Kenji and Yamamoto, Nobuhiko}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.0293-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Antibodies, Blocking; Cell Survival; Cells, Cultured; Cerebral Cortex; DNA Primers; DNA, Complementary; Dendrites; Electroporation; Female; GPI-Linked Proteins; Genetic Vectors; Immunohistochemistry; In Situ Hybridization; Male; Microarray Analysis; Neurons; Neuropeptides; Plasmids; Pregnancy; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Thalamus; Transfection}, Month = {Oct}, Number = {44}, Pages = {15388-402}, pmid = {23115177}, Pst = {ppublish}, Title = {Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons}, Volume = {32}, Year = {2012}, url = {papers/Sato_JNeurosci2012a.pdf}} @article{State:2012, Author = {State, Matthew W and {\v S}estan, Nenad}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1126/science.1224989}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {downloads}, Mesh = {Child Development Disorders, Pervasive; Child, Preschool; Gene Expression Profiling; Gene Expression Regulation, Developmental; Genetic Loci; Humans; Mutation; Neocortex}, Month = {Sep}, Number = {6100}, Pages = {1301-3}, pmid = {22984058}, Pst = {ppublish}, Title = {Neuroscience. The emerging biology of autism spectrum disorders}, Volume = {337}, Year = {2012}, url = {papers/State_Science2012.pdf}} @article{Holmes:2012, Abstract = {Cervical dystonia (CD; spasmodic torticollis) can be evoked by inhibition of substantia nigra pars reticulata (SNpr) in the nonhuman primate (Burbaud et al., 1998; Dybdal et al., 2012). Suppression of GABAergic neurons that project from SNpr results in the disinhibition of the targets to which these neurons project. It therefore should be possible to prevent CD by inhibition of the appropriate nigral target region(s). Here we tested the hypothesis that the deep and intermediate layers of the superior colliculus (DLSC), a key target of nigral projections, are required for the emergence of CD. To test this hypothesis, we pretreated the DLSC of four macaques with the GABA(A) agonist muscimol to determine whether this treatment would prevent CD evoked by muscimol infusions in SNpr. Our data supported this hypothesis: inhibition of DLSC attenuated CD evoked by muscimol in SNpr in all four animals. In two of the four subjects, quadrupedal rotations were evoked by muscimol application into SNpr sites that were distinct from those that induced dystonia. We found that inhibition of DLSC did not significantly alter quadrupedal rotations, suggesting that this response is dissociable from the SNpr-evoked CD. Our results are the first to demonstrate a role of DLSC in mediating the expression of CD. Furthermore, these data reveal a functional relationship between SNpr and DLSC in regulating posture and movement in the nonhuman primate, raising the possibility that the nigrotectal pathway has potential as a target for therapeutic interventions for CD.}, Author = {Holmes, Angela L and Forcelli, Patrick A and DesJardin, Jacqueline T and Decker, Ashley L and Teferra, Menna and West, Elizabeth A and Malkova, Ludise and Gale, Karen}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.2295-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Analysis of Variance; Animals; Bicuculline; Disease Models, Animal; Drug Administration Routes; Female; GABA-A Receptor Agonists; GABA-A Receptor Antagonists; Head Movements; Macaca mulatta; Magnetic Resonance Imaging; Male; Movement; Muscimol; Postural Balance; Sensation Disorders; Substantia Nigra; Superior Colliculi; Torticollis}, Month = {Sep}, Number = {38}, Pages = {13326-32}, pmid = {22993447}, Pst = {ppublish}, Title = {Superior colliculus mediates cervical dystonia evoked by inhibition of the substantia nigra pars reticulata}, Volume = {32}, Year = {2012}, url = {papers/Holmes_JNeurosci2012.pdf}} @article{Anastasiades:2012, Abstract = {The integration of neurons within the developing cerebral cortex is a prolonged process dependent on a combination of molecular and physiological cues. To examine the latter we used laser scanning photostimulation (LSPS) of caged glutamate in conjunction with whole-cell patch-clamp electrophysiology to probe the integration of pyramidal cells in the sensorimotor regions of the mouse neocortex. In the days immediately after postnatal day 5 (P5) the origin of the LSPS-evoked AMPA receptor (AMPAR)-mediated synaptic inputs were diffuse and poorly defined with considerable variability between cells. Over the subsequent week this coalesced and shifted, primarily influenced by an increased contribution from layers 2/3 cells, which became a prominent motif of the afferent input onto layer 5 pyramidal cells regardless of cortical region. To further investigate this particular emergent translaminar connection, we alternated our mapping protocol between two holding potentials (-70 and +40 mV) allowing us to detect exclusively NMDA receptor (NMDAR)-mediated inputs. This revealed distal MK-801-sensitive synaptic inputs that predict the formation of the mature, canonical layer 2/3 to 5 pathway. However, these were a transient feature and had been almost entirely converted to AMPAR synapses at a later age (P16). To examine the role of activity in the recruitment of early NMDAR synapses, we evoked brief periods (20 min) of rhythmic bursting. Short intense periods of activity could cause a prolonged augmentation of the total input onto pyramidal cells up until P12; a time point when the canonical circuit has been instated and synaptic integration shifts to a more consolidatory phase.}, Author = {Anastasiades, Paul G and Butt, Simon J B}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1523/JNEUROSCI.1262-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Action Potentials; Age Factors; Animals; Animals, Newborn; Bicuculline; Biophysics; Brain Mapping; Dizocilpine Maleate; Dose-Response Relationship, Drug; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA-A Receptor Antagonists; Glutamates; Lasers; Magnesium; Mice; Motor Cortex; Neocortex; Neural Pathways; Patch-Clamp Techniques; Photic Stimulation; Pyramidal Cells; Statistics, Nonparametric; Synapses; Time Factors}, Month = {Sep}, Number = {38}, Pages = {13085-99}, pmid = {22993426}, Pst = {ppublish}, Title = {A role for silent synapses in the development of the pathway from layer 2/3 to 5 pyramidal cells in the neocortex}, Volume = {32}, Year = {2012}, url = {papers/Anastasiades_JNeurosci2012.pdf}} @article{Rizo:2012, Author = {Rizo, Josep}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1126/science.1228654}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {downloads}, Mesh = {Optical Tweezers; SNARE Proteins}, Month = {Sep}, Number = {6100}, Pages = {1300-1}, pmid = {22984057}, Pst = {ppublish}, Title = {Cell biology. Staging membrane fusion}, Volume = {337}, Year = {2012}, url = {papers/Rizo_Science2012.pdf}} @article{Sherratt:2012, Author = {Sherratt, Thomas N and Roberts, Gilbert}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1126/science.1226328}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {downloads}, Mesh = {Animals; Behavior, Animal; Biological Evolution; Cooperative Behavior; Female; Male; Sexual Behavior, Animal}, Month = {Sep}, Number = {6100}, Pages = {1304-5}, pmid = {22984060}, Pst = {ppublish}, Title = {Ecology. When paths to cooperation converge}, Volume = {337}, Year = {2012}, url = {papers/Sherratt_Science2012.pdf}} @article{Capotondo:2012, Abstract = {The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.}, Author = {Capotondo, Alessia and Milazzo, Rita and Politi, Letterio Salvatore and Quattrini, Angelo and Palini, Alessio and Plati, Tiziana and Merella, Stefania and Nonis, Alessandro and di Serio, Clelia and Montini, Eugenio and Naldini, Luigi and Biffi, Alessandra}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1073/pnas.1205858109}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {downloads}, Mesh = {Analysis of Variance; Animals; Cell Differentiation; Cell Movement; Flow Cytometry; Green Fluorescent Proteins; Hematopoietic Stem Cell Transplantation; In Situ Nick-End Labeling; Lysosomal Storage Diseases, Nervous System; Mice; Mice, Knockout; Microglia; Transplantation Conditioning}, Month = {Sep}, Number = {37}, Pages = {15018-23}, Pmc = {PMC3443128}, pmid = {22923692}, Pst = {ppublish}, Title = {Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation}, Volume = {109}, Year = {2012}, url = {papers/Capotondo_ProcNatlAcadSciUSA2012.pdf}} @article{Yurovsky:2012, Abstract = {The study of cognitive development hinges, largely, on the analysis of infant looking. But analyses of eye gaze data require the adoption of linking hypotheses: assumptions about the relationship between observed eye movements and underlying cognitive processes. We develop a general framework for constructing, testing, and comparing these hypotheses, and thus for producing new insights into early cognitive development. We first introduce the general framework--applicable to any infant gaze experiment--and then demonstrate its utility by analyzing data from a set of experiments investigating the role of attentional cues in infant learning. The new analysis uncovers significantly more structure in these data, finding evidence of learning that was not found in standard analyses and showing an unexpected relationship between cue use and learning rate. Finally, we discuss general implications for the construction and testing of quantitative linking hypotheses. MATLAB code for sample linking hypotheses can be found on the first author's website.}, Author = {Yurovsky, Daniel and Hidaka, Shohei and Wu, Rachel}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1371/journal.pone.0047419}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {downloads}, Number = {10}, Pages = {e47419}, Pmc = {PMC3482231}, pmid = {23110071}, Pst = {ppublish}, Title = {Quantitative linking hypotheses for infant eye movements}, Volume = {7}, Year = {2012}, url = {papers/Yurovsky_PLoSOne2012.pdf}} @article{Margolis:2012, Abstract = {Sensory maps are reshaped by experience. It is unknown how map plasticity occurs in vivo in functionally diverse neuronal populations because activity of the same cells has not been tracked over long time periods. Here we used repeated two-photon imaging of a genetic calcium indicator to measure whisker-evoked responsiveness of the same layer 2/3 neurons in adult mouse barrel cortex over weeks, first with whiskers intact, then during continued trimming of all but one whisker. Across the baseline period, neurons displayed heterogeneous yet stable responsiveness. During sensory deprivation, responses to trimmed whisker stimulation globally decreased, whereas responses to spared whisker stimulation increased for the least active neurons and decreased for the most active neurons. These findings suggest that recruitment of inactive, 'silent' neurons is part of a convergent redistribution of population activity underlying sensory map plasticity. Sensory-driven responsiveness is a key property controlling experience-dependent activity changes in individual neurons.}, Author = {Margolis, David J and L{\"u}tcke, Henry and Schulz, Kristina and Haiss, Florent and Weber, Bruno and K{\"u}gler, Sebastian and Hasan, Mazahir T and Helmchen, Fritjof}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1038/nn.3240}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {downloads}, Mesh = {Action Potentials; Animals; Brain Mapping; Calcium; Cerebral Cortex; Computer Simulation; Female; Gene Expression Regulation; Luminescent Proteins; Male; Mice; Mice, Inbred C57BL; Models, Biological; Neurons; Neuropil; Optics and Photonics; Physical Stimulation; Sensory Deprivation; Synapsins; Time Factors; Transduction, Genetic; Vibrissae}, Month = {Nov}, Number = {11}, Pages = {1539-46}, pmid = {23086335}, Pst = {ppublish}, Title = {Reorganization of cortical population activity imaged throughout long-term sensory deprivation}, Volume = {15}, Year = {2012}, url = {papers/Margolis_NatNeurosci2012.pdf}} @article{Blanco-Hernandez:2012, Abstract = {The olfactory system, particularly the olfactory epithelium, presents a unique opportunity to study the regenerative capabilities of the brain, because of its ability to recover after damage. In this study, we ablated olfactory sensory neurons with methimazole and followed the anatomical and functional recovery of circuits expressing genetic markers for I7 and M72 receptors (M72-IRES-tau-LacZ and I7-IRES-tau-GFP). Our results show that 45 days after methimazole-induced lesion, axonal projections to the bulb of M72 and I7 populations are largely reestablished. Furthermore, regenerated glomeruli are re-formed within the same areas as those of control, unexposed mice. This anatomical regeneration correlates with functional recovery of a previously learned odorant-discrimination task, dependent on the cognate ligands for M72 and I7. Following regeneration, mice also recover innate responsiveness to TMT and urine. Our findings show that regeneration of neuronal circuits in the olfactory system can be achieved with remarkable precision and underscore the importance of glomerular organization to evoke memory traces stored in the brain.}, Author = {Blanco-Hern{\'a}ndez, Eduardo and Valle-Leija, Pablo and Zomosa-Signoret, Viviana and Drucker-Col{\'\i}n, Ren{\'e} and Vidaltamayo, Rom{\'a}n}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1371/journal.pone.0046338}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {downloads}, Number = {10}, Pages = {e46338}, Pmc = {PMC3468571}, pmid = {23071557}, Pst = {ppublish}, Title = {Odor memory stability after reinnervation of the olfactory bulb}, Volume = {7}, Year = {2012}, url = {papers/Blanco-Hernández_PLoSOne2012.pdf}} @article{Watakabe:2012, Abstract = {We are interested in identifying and characterizing various projection neurons that constitute the neocortical circuit. For this purpose, we developed a novel lentiviral vector that carries the tetracycline transactivator (tTA) and the transgene under the TET Responsive Element promoter (TRE) on a single backbone. By pseudotyping such a vector with modified rabies G-protein, we were able to express palmitoylated-GFP (palGFP) or turboFP635 (RFP) in corticothalamic, corticocortical, and corticopontine neurons of mice. The high-level expression of the transgene achieved by the TET-Off system enabled us to observe characteristic elaboration of neuronal processes for each cell type. At higher magnification, we were able to observe fine structures such as boutons and spines as well. We also injected our retrograde TET-Off vector to the marmoset cortex and proved that it can be used to label the long-distance cortical connectivity of millimeter scale. In conclusion, our novel retrograde tracer provides an attractive option to investigate the morphologies of identified cortical projection neurons of various species.}, Author = {Watakabe, Akiya and Kato, Shigeki and Kobayashi, Kazuto and Takaji, Masafumi and Nakagami, Yuki and Sadakane, Osamu and Ohtsuka, Masanari and Hioki, Hiroyuki and Kaneko, Takeshi and Okuno, Hiroyuki and Kawashima, Takashi and Bito, Haruhiko and Kitamura, Yoshihiro and Yamamori, Tetsuo}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1371/journal.pone.0046157}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {downloads}, Number = {10}, Pages = {e46157}, Pmc = {PMC3465318}, pmid = {23071541}, Pst = {ppublish}, Title = {Visualization of cortical projection neurons with retrograde TET-off lentiviral vector}, Volume = {7}, Year = {2012}, url = {papers/Watakabe_PLoSOne2012.pdf}} @article{Reese:2012, Abstract = {The brain is one of the most studied and highly complex systems in the biological world. While much research has concentrated on studying the brain directly, our focus is the structure of the brain itself: at its core an interconnected network of nodes (neurons). A better understanding of the structural connectivity of the brain should elucidate some of its functional properties. In this paper we analyze the connectome of the nematode Caenorhabditis elegans. Consisting of only 302 neurons, it is one of the better-understood neural networks. Using a Laplacian Matrix of the 279-neuron "giant component" of the network, we use an eigenvalue counting function to look for fractal-like self similarity. This matrix representation is also used to plot visualizations of the neural network in eigenfunction coordinates. Small-world properties of the system are examined, including average path length and clustering coefficient. We test for localization of eigenfunctions, using graph energy and spacial variance on these functions. To better understand results, all calculations are also performed on random networks, branching trees, and known fractals, as well as fractals which have been "rewired" to have small-world properties. We propose algorithms for generating Laplacian matrices of each of these graphs.}, Author = {Reese, Tyler M and Brzoska, Antoni and Yott, Dylan T and Kelleher, Daniel J}, Date-Added = {2013-04-01 16:12:12 +0000}, Date-Modified = {2013-04-01 16:12:27 +0000}, Doi = {10.1371/journal.pone.0040483}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {downloads}, Number = {10}, Pages = {e40483}, Pmc = {PMC3465333}, pmid = {23071485}, Pst = {ppublish}, Title = {Analyzing self-similar and fractal properties of the C. elegans neural network}, Volume = {7}, Year = {2012}, url = {papers/Reese_PLoSOne2012.pdf}} @article{Sugar:2011, Abstract = {A connectome is an indispensable tool for brain researchers, since it quickly provides comprehensive knowledge of the brain's anatomical connections. Such knowledge lies at the basis of understanding network functions. Our first comprehensive and interactive account of brain connections comprised the rat hippocampal-parahippocampal network. We have now added all anatomical connections with the retrosplenial cortex (RSC) as well as the intrinsic connections of this region, because of the interesting functional overlap between these brain regions. The RSC is involved in a variety of cognitive tasks including memory, navigation, and prospective thinking, yet the exact role of the RSC and the functional differences between its subdivisions remain elusive. The connectome presented here may help to define this role by providing an unprecedented interactive and searchable overview of all connections within and between the rat RSC, parahippocampal region and hippocampal formation.}, Author = {Sugar, J{\o}rgen and Witter, Menno P and van Strien, Niels M and Cappaert, Natalie L M}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.3389/fninf.2011.00007}, Journal = {Front Neuroinform}, Journal-Full = {Frontiers in neuroinformatics}, Keywords = {downloads}, Pages = {7}, Pmc = {PMC3147162}, pmid = {21847380}, Pst = {ppublish}, Title = {The retrosplenial cortex: intrinsic connectivity and connections with the (para)hippocampal region in the rat. An interactive connectome}, Volume = {5}, Year = {2011}, url = {papers/Sugar_FrontNeuroinform2011.pdf}} @article{McNaughton:2006, Abstract = {The hippocampal formation can encode relative spatial location, without reference to external cues, by the integration of linear and angular self-motion (path integration). Theoretical studies, in conjunction with recent empirical discoveries, suggest that the medial entorhinal cortex (MEC) might perform some of the essential underlying computations by means of a unique, periodic synaptic matrix that could be self-organized in early development through a simple, symmetry-breaking operation. The scale at which space is represented increases systematically along the dorsoventral axis in both the hippocampus and the MEC, apparently because of systematic variation in the gain of a movement-speed signal. Convergence of spatially periodic input at multiple scales, from so-called grid cells in the entorhinal cortex, might result in non-periodic spatial firing patterns (place fields) in the hippocampus.}, Author = {McNaughton, Bruce L and Battaglia, Francesco P and Jensen, Ole and Moser, Edvard I and Moser, May-Britt}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2014-09-16 14:38:03 +0000}, Doi = {10.1038/nrn1932}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {rat; grid cells; hippocampus; Spatial Behavior; navigation; Entorhinal Cortex; place cells}, Mesh = {Animals; Brain Mapping; Cognition; Hippocampus; Humans; Nerve Net; Neural Pathways}, Month = {Aug}, Number = {8}, Pages = {663-78}, pmid = {16858394}, Pst = {ppublish}, Title = {Path integration and the neural basis of the 'cognitive map'}, Volume = {7}, Year = {2006}, url = {papers/McNaughton_NatRevNeurosci2006.pdf}} @article{Wagner:2006, Abstract = {Retinoic acid is well recognized to promote neuronal differentiation in the embryonic nervous system, but how it influences the postnatal cerebral cortex remains largely unknown. The domain of highest retinoic acid actions in the cortex of the mouse constricts postnatally to a narrow band that includes the dorsal visual stream and the attentional and executive networks. This band of cortex, which is distinguished by the retinoic acid-synthesizing enzyme RALDH3, exhibits signs of delayed maturation and enhanced plasticity compared to the surrounding cortex, as indicated by suppression of parvalbumin, neurofilament, cytochrome oxidase and perineuronal net maturation, and persistence of the embryonic, polysialated form of the neural cell-adhesion molecule PSA-NCAM. During the first postnatal week, the RALDH3-expressing territory translocates in the caudal cortex from the medial limbic lobe to the adjacent neocortex. This topographical shift requires the neurotrophin NT-3 because in mice lacking neuronal NT-3 the RALDH3 enzyme maintains its early postnatal pattern up to adulthood. In the NT-3-null mutants, expression of the markers, whose topography colocalizes with RALDH3 in the normal cortex, matches the abnormal RALDH3 pattern. This indicates that the uneven retinoic acid distribution serves a role in patterning the maturation and to some extent function of the normal postnatal cerebral cortex.}, Author = {Wagner, Elisabeth and Luo, Tuanlian and Sakai, Yasuo and Parada, Luis F and Dr{\"a}ger, Ursula C}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.1111/j.1460-9568.2006.04934.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {downloads}, Mesh = {Aldehyde Oxidoreductases; Animals; Animals, Newborn; Biological Markers; Cell Differentiation; Cerebral Cortex; Electron Transport Complex IV; Gene Expression Regulation, Developmental; Humans; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Cell Adhesion Molecule L1; Neural Pathways; Neurofilament Proteins; Neuronal Plasticity; Neurons; Neurotrophin 3; Parvalbumins; Protein Transport; Retinal Dehydrogenase; Sialic Acids; Tretinoin}, Month = {Jul}, Number = {2}, Pages = {329-40}, pmid = {16836633}, Pst = {ppublish}, Title = {Retinoic acid delineates the topography of neuronal plasticity in postnatal cerebral cortex}, Volume = {24}, Year = {2006}, url = {papers/Wagner_EurJNeurosci2006.pdf}} @article{Grimsley:2011, Abstract = {Adult mice are highly vocal animals, with both males and females vocalizing in same sex and cross sex social encounters. Mouse pups are also highly vocal, producing isolation vocalizations when they are cold or removed from the nest. This study examined patterns in the development of pup isolation vocalizations, and compared these to adult vocalizations. In three litters of CBA/CaJ mice, we recorded isolation vocalizations at ages postnatal day 5 (p5), p7, p9, p11, and p13. Adult vocalizations were obtained in a variety of social situations. Altogether, 28,384 discrete vocal signals were recorded using high-frequency-sensitive equipment and analyzed for syllable type, spectral and temporal features, and the temporal sequencing within bouts. We found that pups produced all but one of the 11 syllable types recorded from adults. The proportions of syllable types changed developmentally, but even the youngest pups produced complex syllables with frequency-time variations. When all syllable types were pooled together for analysis, changes in the peak frequency or the duration of syllables were small, although significant, from p5 through p13. However, individual syllable types showed different, large patterns of change over development, requiring analysis of each syllable type separately. Most adult syllables were substantially lower in frequency and shorter in duration. As pups aged, the complexity of vocal bouts increased, with a greater tendency to switch between syllable types. Vocal bouts from older animals, p13 and adult, had significantly more sequential structure than those from younger mice. Overall, these results demonstrate substantial changes in social vocalizations with age. Future studies are required to identify whether these changes result from developmental processes affecting the vocal tract or control of vocalization, or from vocal learning. To provide a tool for further research, we developed a MATLAB program that generates bouts of vocalizations that correspond to mice of different ages.}, Author = {Grimsley, Jasmine M S and Monaghan, Jessica J M and Wenstrup, Jeffrey J}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.1371/journal.pone.0017460}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {downloads}, Mesh = {Acoustics; Aging; Animals; Animals, Newborn; Female; Male; Mice; Nonlinear Dynamics; Phonetics; Social Behavior; Sound Spectrography; Vocal Cords; Vocalization, Animal}, Number = {3}, Pages = {e17460}, Pmc = {PMC3052362}, pmid = {21408007}, Pst = {epublish}, Title = {Development of social vocalizations in mice}, Volume = {6}, Year = {2011}, url = {papers/Grimsley_PLoSOne2011.pdf}} @article{Taniguchi:2013, Abstract = {Diverse γ-aminobutyric acid-releasing interneurons regulate the functional organization of cortical circuits and derive from multiple embryonic sources. It remains unclear to what extent embryonic origin influences interneuron specification and cortical integration because of difficulties in tracking defined cell types. Here, we followed the developmental trajectory of chandelier cells (ChCs), the most distinct interneurons that innervate the axon initial segment of pyramidal neurons and control action potential initiation. ChCs mainly derive from the ventral germinal zone of the lateral ventricle during late gestation and require the homeodomain protein Nkx2.1 for their specification. They migrate with stereotyped routes and schedule and achieve specific laminar distribution in the cortex. The developmental specification of this bona fide interneuron type likely contributes to the assembly of a cortical circuit motif.}, Author = {Taniguchi, Hiroki and Lu, Jiangteng and Huang, Z Josh}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.1126/science.1227622}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {downloads}, Mesh = {Animals; Cell Lineage; Female; Interneurons; Lateral Ventricles; Mice; Mice, Mutant Strains; Neocortex; Neural Stem Cells; Nuclear Proteins; Pyramidal Cells; Transcription Factors; gamma-Aminobutyric Acid}, Month = {Jan}, Number = {6115}, Pages = {70-4}, pmid = {23180771}, Pst = {ppublish}, Title = {The spatial and temporal origin of chandelier cells in mouse neocortex}, Volume = {339}, Year = {2013}, url = {papers/Taniguchi_Science2013.pdf}} @article{Haider:2013, Abstract = {The activity of the cerebral cortex is thought to depend on the precise relationship between synaptic excitation and inhibition. In the visual cortex, in particular, intracellular measurements have related response selectivity to coordinated increases in excitation and inhibition. These measurements, however, have all been made during anaesthesia, which strongly influences cortical state and therefore sensory processing. The synaptic activity that is evoked by visual stimulation during wakefulness is unknown. Here we measured visually evoked responses--and the underlying synaptic conductances--in the visual cortex of anaesthetized and awake mice. Under anaesthesia, responses could be elicited from a large region of visual space and were prolonged. During wakefulness, responses were more spatially selective and much briefer. Whole-cell patch-clamp recordings of synaptic conductances showed a difference in synaptic inhibition between the two conditions. Under anaesthesia, inhibition tracked excitation in amplitude and spatial selectivity. By contrast, during wakefulness, inhibition was much stronger than excitation and had extremely broad spatial selectivity. We conclude that during wakefulness, cortical responses to visual stimulation are dominated by synaptic inhibition, restricting the spatial spread and temporal persistence of neural activity. These results provide a direct glimpse of synaptic mechanisms that control sensory responses in the awake cortex.}, Author = {Haider, Bilal and H{\"a}usser, Michael and Carandini, Matteo}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.1038/nature11665}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Anesthesia; Animals; Female; Mice; Mice, Inbred C57BL; Models, Neurological; Neural Inhibition; Patch-Clamp Techniques; Photic Stimulation; Synapses; Synaptic Transmission; Time Factors; Visual Cortex; Wakefulness}, Month = {Jan}, Number = {7430}, Pages = {97-100}, Pmc = {PMC3537822}, pmid = {23172139}, Pst = {ppublish}, Title = {Inhibition dominates sensory responses in the awake cortex}, Volume = {493}, Year = {2013}, url = {papers/Haider_Nature2013.pdf}} @article{Lazarenko:2010, Abstract = {At surgical depths of anesthesia, inhalational anesthetics cause a loss of motor response to painful stimuli (i.e., immobilization) that is characterized by profound inhibition of spinal motor circuits. Yet, although clearly depressed, the respiratory motor system continues to provide adequate ventilation under these same conditions. Here, we show that isoflurane causes robust activation of CO(2)/pH-sensitive, Phox2b-expressing neurons located in the retrotrapezoid nucleus (RTN) of the rodent brainstem, in vitro and in vivo. In brainstem slices from Phox2b-eGFP mice, the firing of pH-sensitive RTN neurons was strongly increased by isoflurane, independent of prevailing pH conditions. At least two ionic mechanisms contributed to anesthetic activation of RTN neurons: activation of an Na(+)-dependent cationic current and inhibition of a background K(+) current. Single-cell reverse transcription-PCR analysis of dissociated green fluorescent protein-labeled RTN neurons revealed expression of THIK-1 (TWIK-related halothane-inhibited K(+) channel, K(2P)13.1), a channel that shares key properties with the native RTN current (i.e., suppression by inhalational anesthetics, weak rectification, inhibition by extracellular Na(+), and pH-insensitivity). Isoflurane also increased firing rate of RTN chemosensitive neurons in urethane-anesthetized rats, again independent of CO(2) levels. In these animals, isoflurane transiently enhanced activity of the respiratory system, an effect that was most prominent at low levels of respiratory drive and mediated primarily by an increase in respiratory frequency. These data indicate that inhalational anesthetics cause activation of RTN neurons, which serve an important integrative role in respiratory control; the increased drive provided by enhanced RTN neuronal activity may contribute, in part, to maintaining respiratory motor activity under immobilizing anesthetic conditions.}, Author = {Lazarenko, Roman M and Fortuna, Michal G and Shi, Yingtang and Mulkey, Daniel K and Takakura, Ana C and Moreira, Thiago S and Guyenet, Patrice G and Bayliss, Douglas A}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.1523/JNEUROSCI.1956-10.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Analysis of Variance; Anesthetics, Inhalation; Animals; Animals, Newborn; Blood Pressure; Chemoreceptor Cells; Dose-Response Relationship, Drug; Electric Stimulation; Gene Expression Regulation; Green Fluorescent Proteins; Homeodomain Proteins; Hydrogen-Ion Concentration; Ion Channel Gating; Isoflurane; Membrane Potentials; Mice; Mice, Transgenic; Neural Inhibition; Patch-Clamp Techniques; Phrenic Nerve; Potassium Channels, Tandem Pore Domain; Respiration; Respiratory Center; Transcription Factors}, Month = {Jul}, Number = {27}, Pages = {9324-34}, Pmc = {PMC2910363}, pmid = {20610767}, Pst = {ppublish}, Title = {Anesthetic activation of central respiratory chemoreceptor neurons involves inhibition of a THIK-1-like background K(+) current}, Volume = {30}, Year = {2010}, url = {papers/Lazarenko_JNeurosci2010.pdf}} @article{Meyer-Lindenberg:2012, Abstract = {Mental health and social life are intimately inter-related, as demonstrated by the frequent social deficits of psychiatric patients and the increased rate of psychiatric disorders in people exposed to social environmental adversity. Here, we review emerging evidence that combines epidemiology, social psychology and neuroscience to bring neural mechanisms of social risk factors for mental illness into focus. In doing so, we discuss existing evidence on the effects of common genetic risk factors in social neural pathways and outline the need for integrative approaches to identify the converging mechanisms of social environmental and genetic risk in brain.}, Author = {Meyer-Lindenberg, Andreas and Tost, Heike}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.1038/nn.3083}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {downloads}, Mesh = {Brain; Brain Mapping; Calcium Channels; Emotions; Gene-Environment Interaction; Humans; Mental Disorders; Receptors, Oxytocin; Risk Factors; Social Behavior}, Month = {May}, Number = {5}, Pages = {663-8}, pmid = {22504349}, Pst = {epublish}, Title = {Neural mechanisms of social risk for psychiatric disorders}, Volume = {15}, Year = {2012}, url = {papers/Meyer-Lindenberg_NatNeurosci2012.pdf}} @article{Halje:2012, Abstract = {The standard pharmacological treatment for Parkinson's disease using the dopamine precursor levodopa is unfortunately limited by gradual development of disabling involuntary movements for which the underlying causes are poorly understood. Here we show that levodopa-induced dyskinesia in hemiparkinsonian rats is strongly associated with pronounced 80 Hz local field potential oscillations in the primary motor cortex following levodopa treatment. When this oscillation is interrupted by application of a dopamine antagonist onto the cortical surface the dyskinetic symptoms disappear. The finding that abnormal cortical oscillations are a key pathophysiological mechanism calls for a revision of the prevailing hypothesis that links levodopa-induced dyskinesia to an altered sensitivity to dopamine only in the striatum. Apart from having important implications for the treatment of Parkinson's disease, the discovered pathophysiological mechanism may also play a role in several other psychiatric and neurological conditions involving cortical dysfunction.}, Author = {Halje, P{\"a}r and Tamt{\`e}, Martin and Richter, Ulrike and Mohammed, Mohsin and Cenci, M Angela and Petersson, Per}, Date-Added = {2013-04-01 16:09:48 +0000}, Date-Modified = {2013-04-01 16:10:10 +0000}, Doi = {10.1523/JNEUROSCI.3047-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Algorithms; Animals; Antiparkinson Agents; Cerebral Cortex; Dyskinesia, Drug-Induced; Electrodes, Implanted; Electroencephalography; Evoked Potentials; Female; Fluorescent Antibody Technique; Levodopa; Microelectrodes; Neostriatum; Neurons; Oxidopamine; Parkinson Disease, Secondary; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Receptors, Dopamine D1; Tyrosine 3-Monooxygenase}, Month = {Nov}, Number = {47}, Pages = {16541-51}, pmid = {23175810}, Pst = {ppublish}, Title = {Levodopa-induced dyskinesia is strongly associated with resonant cortical oscillations}, Volume = {32}, Year = {2012}, url = {papers/Halje_JNeurosci2012.pdf}} @article{McMullen:2011, Abstract = {Many multiphoton imaging applications would benefit from a larger field of view; however, large field of views (>mm) require low magnification objectives which have low light collection efficiencies. We demonstrate a light collection system mounted on a low magnification objective that increases fluorescence collection by as much as 20-fold in scattering tissues. This peripheral detector results in an effective numerical aperture of collection >0.8 with a 3-4 mm field of view.}, Author = {McMullen, J D and Kwan, A C and Williams, R M and Zipfel, W R}, Date-Added = {2013-04-01 16:08:21 +0000}, Date-Modified = {2013-04-01 16:08:49 +0000}, Doi = {10.1111/j.1365-2818.2010.03419.x}, Journal = {J Microsc}, Journal-Full = {Journal of microscopy}, Keywords = {downloads}, Mesh = {Abdominal Neoplasms; Animals; Brain; Carcinoma; Mice; Microscopy, Fluorescence; Pathology; Spinal Cord}, Month = {Feb}, Number = {2}, Pages = {119-24}, pmid = {21118215}, Pst = {ppublish}, Title = {Enhancing collection efficiency in large field of view multiphoton microscopy}, Volume = {241}, Year = {2011}, url = {papers/McMullen_JMicrosc2011.pdf}} @article{Kwan:2010, Abstract = {Neural activity can be captured by state-of-the-art optical imaging methods although the analysis of the resulting data sets is often manual and not standardized. Therefore, laboratories using large-scale calcium imaging eagerly await software toolboxes that can automate the process of identifying cells and inferring spikes. An algorithm proposed and implemented in a recent paper by Mukamel et al. [Neuron 63, 747-760 (2009)] used independent component analysis and offers significant improvements over conventional methods. The approach should be widely applicable, as tested with data obtained from the mouse cerebellum, neocortex, and spinal cord. The emergence of analysis tools in parallel with the rapid advances in optical imaging is an exciting development that will stimulate new discoveries and further elucidate the functions of neural circuits.}, Author = {Kwan, Alex C}, Date-Added = {2013-04-01 16:08:21 +0000}, Date-Modified = {2013-04-01 16:08:49 +0000}, Doi = {10.2976/1.3284977}, Journal = {HFSP J}, Journal-Full = {HFSP journal}, Keywords = {downloads}, Month = {Feb}, Number = {1}, Pages = {1-5}, Pmc = {PMC2880024}, pmid = {20676302}, Pst = {ppublish}, Title = {Toward reconstructing spike trains from large-scale calcium imaging data}, Volume = {4}, Year = {2010}, url = {papers/Kwan_HFSPJ2010.pdf}} @article{Li:2012, Abstract = {The usefulness of genetically encoded probes for optical monitoring of neuronal activity and brain circuits would be greatly advanced by the generation of multiple indicators with non-overlapping color spectra. Most existing indicators are derived from or spectrally convergent on GFP. We generated a bright, red, pH-sensitive fluorescent protein, pHTomato, that can be used in parallel with green probes to monitor neuronal activity. SypHTomato, made by fusing pHTomato to the vesicular membrane protein synaptophysin, reported activity-dependent exocytosis as efficiently as green reporters. When expressed with the GFP-based indicator GCaMP3 in the same neuron, sypHTomato enabled concomitant imaging of transmitter release and presynaptic Ca(2+) transients at single nerve terminals. Expressing sypHTomato and GCaMP3 in separate cells enabled the simultaneous determination of presynaptic vesicular turnover and postsynaptic sub- and supra-threshold responses from a connected pair of neurons. With these new tools, we observed a close size matching between pre- and postsynaptic compartments, as well as interesting target cell-dependent regulation of presynaptic vesicle pools. Lastly, by coupling expression of pHTomato- and GFP-based probes with distinct variants of channelrhodopsin, we provided proof-of-principle for an all-optical approach to multiplex control and tracking of distinct circuit pathways.}, Author = {Li, Yulong and Tsien, Richard W}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1038/nn.3126}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {downloads}, Mesh = {Cells, Cultured; Exocytosis; Fluorescent Dyes; HEK293 Cells; Hippocampus; Humans; Hydrogen-Ion Concentration; Luminescent Proteins; Nerve Net; Synaptic Potentials; Synaptic Transmission}, Month = {Jul}, Number = {7}, Pages = {1047-53}, pmid = {22634730}, Pst = {epublish}, Title = {pHTomato, a red, genetically encoded indicator that enables multiplex interrogation of synaptic activity}, Volume = {15}, Year = {2012}, url = {papers/Li_NatNeurosci2012.pdf}} @article{Koralek:2012, Abstract = {The ability to learn new skills and perfect them with practice applies not only to physical skills but also to abstract skills, like motor planning or neuroprosthetic actions. Although plasticity in corticostriatal circuits has been implicated in learning physical skills, it remains unclear if similar circuits or processes are required for abstract skill learning. Here we use a novel behavioural task in rodents to investigate the role of corticostriatal plasticity in abstract skill learning. Rodents learned to control the pitch of an auditory cursor to reach one of two targets by modulating activity in primary motor cortex irrespective of physical movement. Degradation of the relation between action and outcome, as well as sensory-specific devaluation and omission tests, demonstrate that these learned neuroprosthetic actions are intentional and goal-directed, rather than habitual. Striatal neurons change their activity with learning, with more neurons modulating their activity in relation to target-reaching as learning progresses. Concomitantly, strong relations between the activity of neurons in motor cortex and the striatum emerge. Specific deletion of striatal NMDA receptors impairs the development of this corticostriatal plasticity, and disrupts the ability to learn neuroprosthetic skills. These results suggest that corticostriatal plasticity is necessary for abstract skill learning, and that neuroprosthetic movements capitalize on the neural circuitry involved in natural motor learning.}, Author = {Koralek, Aaron C and Jin, Xin and Long, 2nd, John D and Costa, Rui M and Carmena, Jose M}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1038/nature10845}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Acoustic Stimulation; Algorithms; Animals; Cues; Learning; Male; Man-Machine Systems; Mice; Motor Cortex; Motor Skills; Movement; Neostriatum; Neuronal Plasticity; Prostheses and Implants; Psychomotor Performance; Rats; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate; Reward}, Month = {Mar}, Number = {7389}, Pages = {331-5}, Pmc = {PMC3477868}, pmid = {22388818}, Pst = {epublish}, Title = {Corticostriatal plasticity is necessary for learning intentional neuroprosthetic skills}, Volume = {483}, Year = {2012}, url = {papers/Koralek_Nature2012.pdf}} @article{Kinoshita:2012, Abstract = {It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates. However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex--PN--motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.}, Author = {Kinoshita, Masaharu and Matsui, Ryosuke and Kato, Shigeki and Hasegawa, Taku and Kasahara, Hironori and Isa, Kaoru and Watakabe, Akiya and Yamamori, Tetsuo and Nishimura, Yukio and Alstermark, Bror and Watanabe, Dai and Kobayashi, Kazuto and Isa, Tadashi}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1038/nature11206}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Animals; Dependovirus; Green Fluorescent Proteins; Hand; Macaca; Metalloendopeptidases; Motor Cortex; Motor Neurons; Neurosciences; Synaptic Transmission; Tetanus Toxin}, Month = {Jul}, Number = {7406}, Pages = {235-8}, pmid = {22722837}, Pst = {ppublish}, Title = {Genetic dissection of the circuit for hand dexterity in primates}, Volume = {487}, Year = {2012}, url = {papers/Kinoshita_Nature2012.pdf}} @article{Park:2009, Abstract = {Constructing a rich and continuous visual experience requires computing specific details across views as well as integrating similarities across views. In this paper, we report functional magnetic resonance imaging (fMRI) evidence that these distinct computations may occur in two scene-sensitive regions in the brain, the parahippocampal place area (PPA) and retrosplenial cortex (RSC). Participants saw different snapshot views from panoramic scenes, which represented clearly different views, but appeared to come from the same scene. Using fMRI adaptation, we tested whether the PPA and RSC treated these panoramic views as the same or different. In the panoramic condition, three different views from a single panoramic scene were presented. We did not find any attenuation for panoramic repeats in the PPA, showing viewpoint-specificity. In contrast, RSC showed significant attenuation for the panoramic condition, showing viewpoint-integration. However, when the panoramic views were not presented in a continuous way, both the specificity in the PPA and the integration in RSC were lost. These results demonstrate that the PPA and RSC compute different properties of scenes: the PPA focuses on selective discrimination of different views while RSC focuses on the integration of scenes under the same visual context. These complementary functions of the PPA and RSC enable both specific and integrative representations of scenes across several viewpoints.}, Author = {Park, Soojin and Chun, Marvin M}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1016/j.neuroimage.2009.04.058}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Keywords = {downloads}, Mesh = {Adult; Brain Mapping; Cerebral Cortex; Cues; Evoked Potentials, Visual; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Pattern Recognition, Visual; Young Adult}, Month = {Oct}, Number = {4}, Pages = {1747-56}, Pmc = {PMC2753672}, pmid = {19398014}, Pst = {ppublish}, Title = {Different roles of the parahippocampal place area (PPA) and retrosplenial cortex (RSC) in panoramic scene perception}, Volume = {47}, Year = {2009}, url = {papers/Park_Neuroimage2009.pdf}} @article{Tsai:2009a, Abstract = {It is well known that the density of neurons varies within the adult brain. In neocortex, this includes variations in neuronal density between different lamina as well as between different regions. Yet the concomitant variation of the microvessels is largely uncharted. Here, we present automated histological, imaging, and analysis tools to simultaneously map the locations of all neuronal and non-neuronal nuclei and the centerlines and diameters of all blood vessels within thick slabs of neocortex from mice. Based on total inventory measurements of different cortical regions ( approximately 10(7) cells vectorized across brains), these methods revealed: (1) In three dimensions, the mean distance of the center of neuronal somata to the closest microvessel was 15 mum. (2) Volume samples within lamina of a given region show that the density of microvessels does not match the strong laminar variation in neuronal density. This holds for both agranular and granular cortex. (3) Volume samples in successive radii from the midline to the ventral-lateral edge, where each volume summed the number of cells and microvessels from the pia to the white matter, show a significant correlation between neuronal and microvessel densities. These data show that while neuronal and vascular densities do not track each other on the 100 mum scale of cortical lamina, they do track each other on the 1-10 mm scale of the cortical mantle. The absence of a disproportionate density of blood vessels in granular lamina is argued to be consistent with the initial locus of functional brain imaging signals.}, Author = {Tsai, Philbert S and Kaufhold, John P and Blinder, Pablo and Friedman, Beth and Drew, Patrick J and Karten, Harvey J and Lyden, Patrick D and Kleinfeld, David}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1523/JNEUROSCI.3287-09.2009}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Cell Count; Cell Nucleus; Cerebral Cortex; Mice; Mice, Inbred C57BL; Microvessels; Neurons; Rats; Rats, Sprague-Dawley}, Month = {Nov}, Number = {46}, Pages = {14553-70}, pmid = {19923289}, Pst = {ppublish}, Title = {Correlations of neuronal and microvascular densities in murine cortex revealed by direct counting and colocalization of nuclei and vessels}, Volume = {29}, Year = {2009}, url = {papers/Tsai_JNeurosci2009.pdf}} @article{Erzurumlu:2012, Abstract = {In primary sensory neocortical areas of mammals, the distribution of sensory receptors is mapped with topographic precision and amplification in proportion to the peripheral receptor density. The visual, somatosensory and auditory cortical maps are established during a critical period in development. Throughout this window in time, the developing cortical maps are vulnerable to deleterious effects of sense organ damage or sensory deprivation. The rodent barrel cortex offers an invaluable model system with which to investigate the mechanisms underlying the formation of topographic maps and their plasticity during development. Five rows of mystacial vibrissa (whisker) follicles on the snout and an array of sinus hairs are represented by layer IV neural modules ('barrels') and thalamocortical axon terminals in the primary somatosensory cortex. Perinatal damage to the whiskers or the sensory nerve innervating them irreversibly alters the structural organization of the barrels. Earlier studies emphasized the role of the sensory periphery in dictating whisker-specific brain maps and patterns. Recent advances in molecular genetics and analyses of genetically altered mice allow new insights into neural pattern formation in the neocortex and the mechanisms underlying critical period plasticity. Here, we review the development and patterning of the barrel cortex and the critical period plasticity.}, Author = {Erzurumlu, Reha S and Gaspar, Patricia}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1111/j.1460-9568.2012.08075.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {downloads}, Mesh = {Afferent Pathways; Animals; Critical Period (Psychology); Humans; Mice; Models, Biological; Neuronal Plasticity; Neurons; Somatosensory Cortex; Vibrissae}, Month = {May}, Number = {10}, Pages = {1540-53}, Pmc = {PMC3359866}, pmid = {22607000}, Pst = {ppublish}, Title = {Development and critical period plasticity of the barrel cortex}, Volume = {35}, Year = {2012}, url = {papers/Erzurumlu_EurJNeurosci2012.pdf}} @article{Hochberg:2012, Abstract = {Paralysis following spinal cord injury, brainstem stroke, amyotrophic lateral sclerosis and other disorders can disconnect the brain from the body, eliminating the ability to perform volitional movements. A neural interface system could restore mobility and independence for people with paralysis by translating neuronal activity directly into control signals for assistive devices. We have previously shown that people with long-standing tetraplegia can use a neural interface system to move and click a computer cursor and to control physical devices. Able-bodied monkeys have used a neural interface system to control a robotic arm, but it is unknown whether people with profound upper extremity paralysis or limb loss could use cortical neuronal ensemble signals to direct useful arm actions. Here we demonstrate the ability of two people with long-standing tetraplegia to use neural interface system-based control of a robotic arm to perform three-dimensional reach and grasp movements. Participants controlled the arm and hand over a broad space without explicit training, using signals decoded from a small, local population of motor cortex (MI) neurons recorded from a 96-channel microelectrode array. One of the study participants, implanted with the sensor 5 years earlier, also used a robotic arm to drink coffee from a bottle. Although robotic reach and grasp actions were not as fast or accurate as those of an able-bodied person, our results demonstrate the feasibility for people with tetraplegia, years after injury to the central nervous system, to recreate useful multidimensional control of complex devices directly from a small sample of neural signals.}, Author = {Hochberg, Leigh R and Bacher, Daniel and Jarosiewicz, Beata and Masse, Nicolas Y and Simeral, John D and Vogel, Joern and Haddadin, Sami and Liu, Jie and Cash, Sydney S and van der Smagt, Patrick and Donoghue, John P}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1038/nature11076}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Aged; Arm; Calibration; Drinking; Female; Hand; Hand Strength; Humans; Male; Man-Machine Systems; Microelectrodes; Middle Aged; Motor Cortex; Movement; Psychomotor Performance; Quadriplegia; Robotics; Time Factors}, Month = {May}, Number = {7398}, Pages = {372-5}, pmid = {22596161}, Pst = {epublish}, Title = {Reach and grasp by people with tetraplegia using a neurally controlled robotic arm}, Volume = {485}, Year = {2012}, url = {papers/Hochberg_Nature2012.pdf}} @article{Ahrens:2012, Abstract = {A fundamental question in neuroscience is how entire neural circuits generate behaviour and adapt it to changes in sensory feedback. Here we use two-photon calcium imaging to record the activity of large populations of neurons at the cellular level, throughout the brain of larval zebrafish expressing a genetically encoded calcium sensor, while the paralysed animals interact fictively with a virtual environment and rapidly adapt their motor output to changes in visual feedback. We decompose the network dynamics involved in adaptive locomotion into four types of neuronal response properties, and provide anatomical maps of the corresponding sites. A subset of these signals occurred during behavioural adjustments and are candidates for the functional elements that drive motor learning. Lesions to the inferior olive indicate a specific functional role for olivocerebellar circuitry in adaptive locomotion. This study enables the analysis of brain-wide dynamics at single-cell resolution during behaviour.}, Author = {Ahrens, Misha B and Li, Jennifer M and Orger, Michael B and Robson, Drew N and Schier, Alexander F and Engert, Florian and Portugues, Ruben}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1038/nature11057}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {downloads}, Mesh = {Adaptation, Physiological; Animals; Animals, Genetically Modified; Brain; Larva; Learning; Locomotion; Models, Neurological; Nerve Net; Neurons; Neuropil; Photic Stimulation; Psychomotor Performance; Single-Cell Analysis; Zebrafish}, Month = {May}, Number = {7399}, Pages = {471-7}, pmid = {22622571}, Pst = {epublish}, Title = {Brain-wide neuronal dynamics during motor adaptation in zebrafish}, Volume = {485}, Year = {2012}, url = {papers/Ahrens_Nature2012.pdf}} @article{Allene:2012, Abstract = {During early postnatal development, neuronal networks successively produce various forms of spontaneous patterned activity that provide key signals for circuit maturation. Initially, in both rodent hippocampus and neocortex, coordinated activity emerges in the form of synchronous plateau assemblies (SPAs) that are initiated by sparse groups of gap-junction-coupled oscillating neurons. Subsequently, SPAs are replaced by synapse-driven giant depolarizing potentials (GDPs). Whether these sequential changes in mechanistically distinct network activities correlate with modifications in single-cell properties is unknown. To determine this, we studied the morphophysiological fate of single SPA cells as a function of development. We focused on CA3 GABAergic interneurons, which are centrally involved in generating GDPs in the hippocampus. As the network matures, GABAergic neurons are engaged more in GDPs and less in SPAs. Using inducible genetic fate mapping, we show that the individual involvement of GABAergic neurons in SPAs is correlated to their temporal origin. In addition, we demonstrate that the SPA-to-GDP transition is paralleled by a remarkable maturation in the morphophysiological properties of GABAergic neurons. Compared with those involved in GDPs, interneurons participating in SPAs possess immature intrinsic properties, receive synaptic inputs spanning a wide amplitude range, and display large somata as well as membrane protrusions. Thus, a developmental switch in the morphophysiological properties of GABAergic interneurons as they progress from SPAs to GDPs marks the emergence of synapse-driven network oscillations.}, Author = {Allene, Camille and Picardo, Michel A and Becq, H{\'e}l{\`e}ne and Miyoshi, Goichi and Fishell, Gord and Cossart, Rosa}, Date-Added = {2013-04-01 16:06:55 +0000}, Date-Modified = {2013-04-01 16:07:16 +0000}, Doi = {10.1523/JNEUROSCI.0081-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Animals, Newborn; Female; Gene Knock-In Techniques; Hippocampus; Interneurons; Male; Mice; Mice, Transgenic; Nerve Net; Organ Culture Techniques}, Month = {May}, Number = {19}, Pages = {6688-98}, Pmc = {PMC3371585}, pmid = {22573691}, Pst = {ppublish}, Title = {Dynamic changes in interneuron morphophysiological properties mark the maturation of hippocampal network activity}, Volume = {32}, Year = {2012}, url = {papers/Allene_JNeurosci2012.pdf}} @article{Beurdeley:2012, Abstract = {Specific transfer of (orthodenticle homeobox 2) Otx2 homeoprotein into GABAergic interneurons expressing parvalbumin (PV) is necessary and sufficient to open, then close, a critical period (CP) of plasticity in the developing mouse visual cortex. The accumulation of endogenous Otx2 in PV cells suggests the presence of specific Otx2 binding sites. Here, we find that perineuronal nets (PNNs) on the surfaces of PV cells permit the specific, constitutive capture of Otx2. We identify a 15 aa domain containing an arginine-lysine doublet (RK peptide) within Otx2, bearing prototypic traits of a glycosaminoglycan (GAG) binding sequence that mediates Otx2 binding to PNNs, and specifically to chondroitin sulfate D and E, with high affinity. Accordingly, PNN hydrolysis by chondroitinase ABC reduces the amount of endogenous Otx2 in PV cells. Direct infusion of RK peptide similarly disrupts endogenous Otx2 localization to PV cells, reduces PV and PNN expression, and reopens plasticity in adult mice. The closure of one eye during this transient window reduces cortical acuity and is specific to the RK motif, as an Alanine-Alanine variant or a scrambled peptide fails to reactivate plasticity. Conversely, this transient reopening of plasticity in the adult restores binocular vision in amblyopic mice. Thus, one function of PNNs is to facilitate the persistent internalization of Otx2 by PV cells to maintain CP closure. The pharmacological use of the Otx2 GAG binding domain offers a novel, potent therapeutic tool with which to restore cortical plasticity in the mature brain.}, Author = {Beurdeley, Marine and Spatazza, Julien and Lee, Henry H C and Sugiyama, Sayaka and Bernard, Cl{\'e}mence and Di Nardo, Ariel A and Hensch, Takao K and Prochiantz, Alain}, Date-Added = {2013-04-01 16:06:07 +0000}, Date-Modified = {2013-04-01 16:06:22 +0000}, Doi = {10.1523/JNEUROSCI.0394-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Age Factors; Animals; Extracellular Matrix; GABAergic Neurons; Interneurons; Male; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Otx Transcription Factors; Protein Binding; Visual Cortex}, Month = {Jul}, Number = {27}, Pages = {9429-37}, Pmc = {PMC3419577}, pmid = {22764251}, Pst = {ppublish}, Title = {Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex}, Volume = {32}, Year = {2012}, url = {papers/Beurdeley_JNeurosci2012.pdf}} @article{Guo:2012, Abstract = {Topographically organized maps of the sensory receptor epithelia are regarded as cornerstones of cortical organization as well as valuable readouts of diverse biological processes ranging from evolution to neural plasticity. However, maps are most often derived from multiunit activity recorded in the thalamic input layers of anesthetized animals using near-threshold stimuli. Less distinct topography has been described by studies that deviated from the formula above, which brings into question the generality of the principle. Here, we explicitly compared the strength of tonotopic organization at various depths within core and belt regions of the auditory cortex using electrophysiological measurements ranging from single units to delta-band local field potentials (LFP) in the awake and anesthetized mouse. Unit recordings in the middle cortical layers revealed a precise tonotopic organization in core, but not belt, regions of auditory cortex that was similarly robust in awake and anesthetized conditions. In core fields, tonotopy was degraded outside the middle layers or when LFP signals were substituted for unit activity, due to an increasing proportion of recording sites with irregular tuning for pure tones. However, restricting our analysis to clearly defined receptive fields revealed an equivalent tonotopic organization in all layers of the cortical column and for LFP activity ranging from gamma to theta bands. Thus, core fields represent a transition between topographically organized simple receptive field arrangements that extend throughout all layers of the cortical column and the emergence of nontonotopic representations outside the input layers that are further elaborated in the belt fields.}, Author = {Guo, Wei and Chambers, Anna R and Darrow, Keith N and Hancock, Kenneth E and Shinn-Cunningham, Barbara G and Polley, Daniel B}, Date-Added = {2013-04-01 16:05:33 +0000}, Date-Modified = {2013-04-01 16:05:43 +0000}, Doi = {10.1523/JNEUROSCI.0065-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {downloads}, Mesh = {Animals; Auditory Cortex; Auditory Pathways; Auditory Perception; Brain Mapping; Electrophysiology; Evoked Potentials, Auditory; Female; Mice; Mice, Inbred CBA; Neural Pathways; Neurons; Signal Processing, Computer-Assisted; Signal Transduction}, Month = {Jul}, Number = {27}, Pages = {9159-72}, Pmc = {PMC3402176}, pmid = {22764225}, Pst = {ppublish}, Title = {Robustness of cortical topography across fields, laminae, anesthetic states, and neurophysiological signal types}, Volume = {32}, Year = {2012}, url = {papers/Guo_JNeurosci2012.pdf}} @article{Sansom:2009, Abstract = {In the developing brain, gradients are commonly used to divide neurogenic regions into distinct functional domains. In this article, we discuss the functions of morphogen and gene expression gradients in the assembly of the nervous system in the context of the development of the cerebral cortex. The cerebral cortex is a mammal-specific region of the forebrain that functions at the top of the neural hierarchy to process and interpret sensory information, plan and organize tasks, and to control motor functions. The mature cerebral cortex is a modular structure, consisting of anatomically and functionally distinct areas. Those areas of neurons are generated from a uniform neuroepithelial sheet by two forms of gradients: graded extracellular signals and a set of transcription factor gradients operating across the field of neocortical stem cells. Fgf signaling from the rostral pole of the cerebral cortex sets up gradients of expression of transcription factors by both activating and repressing gene expression. However, in contrast to the spinal cord and the early Drosophila embryo, these gradients are not subsequently resolved into molecularly distinct domains of gene expression. Instead, graded information in stem cells is translated into discrete, region-specific gene expression in the postmitotic neuronal progeny of the stem cells.}, Author = {Sansom, Stephen N and Livesey, Frederick J}, Date-Added = {2013-04-01 16:02:24 +0000}, Date-Modified = {2013-04-23 17:54:57 +0000}, Doi = {10.1101/cshperspect.a002519}, Journal = {Cold Spring Harb Perspect Biol}, Journal-Full = {Cold Spring Harbor perspectives in biology}, Keywords = {Cerebral Cortex; Neocortex; patterning; topographic map; development; Gene Expression; toread; neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Mesh = {Animals; Brain; Cerebral Cortex; Drosophila; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Mice; Models, Biological; Motor Cortex; Nervous System; Neurons; Spinal Cord; Stem Cells; Transcription Factors}, Month = {Aug}, Number = {2}, Pages = {a002519}, Pmc = {PMC2742095}, pmid = {20066088}, Pst = {ppublish}, Title = {Gradients in the brain: the control of the development of form and function in the cerebral cortex}, Volume = {1}, Year = {2009}, url = {papers/Sansom_ColdSpringHarbPerspectBiol2009.pdf}} @article{Courchet:2012, Abstract = {In this issue of Neuron, Harwell et al. (2012) identify a new role for the secreted molecule Shh and its receptor Boc in synapse formation. These results add an unexpected new player to the expanding list of extracellular cues regulating the spatial specificity of synapse formation.}, Author = {Courchet, Julien and Polleux, Franck}, Date-Added = {2013-04-01 15:51:29 +0000}, Date-Modified = {2013-04-01 15:52:12 +0000}, Doi = {10.1016/j.neuron.2012.03.008}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {development; patterning; Cerebral Cortex; Neocortex; Laterality}, Mesh = {Animals; Cerebral Cortex; Gene Expression Regulation, Developmental; Hedgehog Proteins; Nerve Net; Neurons; Pyramidal Tracts}, Month = {Mar}, Number = {6}, Pages = {1055-8}, pmid = {22445332}, Pst = {ppublish}, Title = {Sonic hedgehog, BOC, and synaptic development: new players for an old game}, Volume = {73}, Year = {2012}, url = {papers/Courchet_Neuron2012.pdf}} @article{Johansen-Berg:2012, Abstract = {How rapidly does learning shape our brains? A new study in this issue of Neuron by Sagi et al. (2012) that uses diffusion magnetic resonance imaging in both humans and rats suggests that just 2 hr of spatial learning is sufficient to change brain structure.}, Author = {Johansen-Berg, Heidi and Baptista, Cassandra Sampaio and Thomas, Adam G}, Date-Added = {2013-04-01 15:49:05 +0000}, Date-Modified = {2013-04-01 15:51:08 +0000}, Doi = {10.1016/j.neuron.2012.03.001}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {toread; plasticity; structural remodeling; Structure-Activity Relationship; human; MRI; DTI}, Mesh = {Animals; Brain; Brain Mapping; Female; Humans; Learning; Male; Neuronal Plasticity}, Month = {Mar}, Number = {6}, Pages = {1058-60}, Pmc = {PMC3353540}, pmid = {22445333}, Pst = {ppublish}, Title = {Human structural plasticity at record speed}, Volume = {73}, Year = {2012}, url = {papers/Johansen-Berg_Neuron2012.pdf}} @article{Eglen:2003, Abstract = {A role for spontaneous spiking activity in shaping neuronal circuits has frequently been debated. Analyses of retinotopy in mutant mice with reduced correlated firing among neighboring retinal cells by Grubb et al. and McLaughlin et al. in this issue of Neuron indicate the importance of patterned spontaneous activity for retinotopic map refinement in subcortical visual targets.}, Author = {Eglen, Stephen J and Demas, Jay and Wong, Rachel O L}, Date-Added = {2013-04-01 15:47:38 +0000}, Date-Modified = {2013-04-01 15:48:47 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {spontaneous activity; development; topographic map; patterning; Cerebral Cortex; Neocortex; visual system; retinal waves}, Mesh = {Action Potentials; Animals; Humans; Neural Pathways; Photic Stimulation; Retina; Retinal Ganglion Cells}, Month = {Dec}, Number = {6}, Pages = {1053-5}, pmid = {14687538}, Pst = {ppublish}, Title = {Mapping by waves. Patterned spontaneous activity regulates retinotopic map refinement}, Volume = {40}, Year = {2003}, url = {papers/Eglen_Neuron2003.pdf}} @article{Harwell:2012, Abstract = {The precise connectivity of inputs and outputs is critical for cerebral cortex function; however, the cellular mechanisms that establish these connections are poorly understood. Here, we show that the secreted molecule Sonic Hedgehog (Shh) is involved in synapse formation of a specific cortical circuit. Shh is expressed in layer V corticofugal projection neurons and the Shh receptor, Brother of CDO (Boc), is expressed in local and callosal projection neurons of layer II/III that synapse onto the subcortical projection neurons. Layer V neurons of mice lacking functional Shh exhibit decreased synapses. Conversely, the loss of functional Boc leads to a reduction in the strength of synaptic connections onto layer Vb, but not layer II/III, pyramidal neurons. These results demonstrate that Shh is expressed in postsynaptic target cells while Boc is expressed in a complementary population of presynaptic input neurons, and they function to guide the formation of cortical microcircuitry. VIDEO ABSTRACT:}, Author = {Harwell, Corey C and Parker, Philip R L and Gee, Steven M and Okada, Ami and McConnell, Susan K and Kreitzer, Anatol C and Kriegstein, Arnold R}, Date-Added = {2013-04-01 15:45:55 +0000}, Date-Modified = {2013-04-01 15:47:20 +0000}, Doi = {10.1016/j.neuron.2012.02.009}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {toread; development; Neocortex; Gene Expression; Cerebral Cortex; patterning; lateralization}, Mesh = {Age Factors; Animals; Animals, Newborn; Cerebral Cortex; Corpus Callosum; DNA-Binding Proteins; Dendritic Spines; Electric Stimulation; Electroporation; Fluorobenzenes; Functional Laterality; Furans; Gene Expression Regulation, Developmental; Hedgehog Proteins; Immunoglobulin G; Luminescent Proteins; Matrix Attachment Region Binding Proteins; Membrane Potentials; Mice; Mice, Transgenic; Mutation; Nerve Net; Neurons; Nuclear Proteins; Patch-Clamp Techniques; Phosphopyruvate Hydratase; Pyramidal Tracts; RNA, Small Interfering; Receptors, Cell Surface; Repressor Proteins; Rhodopsin; Silver Staining; Stilbamidines; Synapses; Synaptophysin; Transcription Factors; Tumor Suppressor Proteins; gamma-Aminobutyric Acid}, Month = {Mar}, Number = {6}, Pages = {1116-26}, Pmc = {PMC3551478}, pmid = {22445340}, Pst = {ppublish}, Title = {Sonic hedgehog expression in corticofugal projection neurons directs cortical microcircuit formation}, Volume = {73}, Year = {2012}, url = {papers/Harwell_Neuron2012.pdf}} @article{Schutz-Bosbach:2007, Abstract = {A direct relationship between perception and action implies bi-directionality, and predicts not only effects of perception on action but also effects of action on perception. Modern theories of social cognition have intensively examined the relation from perception to action and propose that mirroring the observed actions of others underlies action understanding. Here, we suggest that this view is incomplete, as it neglects the perspective of the actor. We will review empirical evidence showing the effects of self-generated action on perceptual judgments. We propose that producing action might prime perception in a way that observers are selectively sensitive to related or similar actions of conspecifics. Therefore, perceptual resonance, not motor resonance, might be decisive for grounding sympathy and empathy and, thus, successful social interactions.}, Author = {Sch{\"u}tz-Bosbach, Simone and Prinz, Wolfgang}, Date-Added = {2013-04-01 15:25:56 +0000}, Date-Modified = {2013-04-01 15:25:56 +0000}, Doi = {10.1016/j.tics.2007.06.005}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Mesh = {Auditory Perception; Brain Mapping; Cerebral Cortex; Cognition; Concept Formation; Humans; Imagination; Interpersonal Relations; Judgment; Kinesthesis; Motor Activity; Neurons; Perception; Psychomotor Performance; Self Concept; Visual Perception}, Month = {Aug}, Number = {8}, Pages = {349-55}, pmid = {17629544}, Pst = {ppublish}, Title = {Perceptual resonance: action-induced modulation of perception}, Volume = {11}, Year = {2007}, url = {papers/Schütz-Bosbach_TrendsCognSci2007.pdf}} @article{Nataraj:2010, Abstract = {In visual cortex monocular deprivation (MD) during a critical period (CP) reduces the ability of the deprived eye to activate cortex, but the underlying cellular plasticity mechanisms are incompletely understood. Here we show that MD reduces the intrinsic excitability of layer 5 (L5) pyramidal neurons and enhances long-term potentiation of intrinsic excitability (LTP-IE). Further, MD and LTP-IE induce reciprocal changes in K(v)2.1 current, and LTP-IE reverses the effects of MD on intrinsic excitability. Taken together these data suggest that MD reduces intrinsic excitability by preventing sensory-drive induced LTP-IE. The effects of MD on excitability were correlated with the classical visual system CP, and (like the functional effects of MD) could be rapidly reversed when vision was restored. These data establish LTP-IE as a candidate mechanism mediating loss of visual responsiveness within L5, and suggest that intrinsic plasticity plays an important role in experience-dependent refinement of visual cortical circuits.}, Author = {Nataraj, Kiran and Le Roux, Nicolas and Nahmani, Marc and Lefort, Sandrine and Turrigiano, Gina}, Date-Added = {2013-04-01 15:23:07 +0000}, Date-Modified = {2013-04-01 15:23:17 +0000}, Doi = {10.1016/j.neuron.2010.09.033}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {downloads}, Mesh = {Animals; Animals, Newborn; Mice; Neural Inhibition; Neuronal Plasticity; Neurons; Pyramidal Cells; Rats; Rats, Long-Evans; Sensory Deprivation; Visual Cortex; Visual Perception}, Month = {Nov}, Number = {4}, Pages = {750-62}, Pmc = {PMC2990987}, pmid = {21092863}, Pst = {ppublish}, Title = {Visual deprivation suppresses L5 pyramidal neuron excitability by preventing the induction of intrinsic plasticity}, Volume = {68}, Year = {2010}, url = {papers/Nataraj_Neuron2010.pdf}} @article{Zheng:2004, Abstract = {Dual patch-clamp recording and Ca2+ uncaging revealed Ca2+-dependent corelease of ACh and GABA from, and the presence of reciprocal nicotinic and GABAergic synapses between, starburst cells in the perinatal rabbit retina. With maturation, the nicotinic synapses between starburst cells dramatically diminished, whereas the GABAergic synapses remained and changed from excitatory to inhibitory, indicating a coordinated conversion of the starburst network excitability from an early hyperexcitatory to a mature nonepileptic state. We show that this transition allows the starburst cells to use their neurotransmitters for two completely different functions. During early development, the starburst network mediates recurrent excitation and spontaneous retinal waves, which are important for visual system development. After vision begins, starburst cells release GABA in a prolonged and Ca2+-dependent manner and inhibit each other laterally via direct GABAergic synapses, which may be important for visual integration, such as the detection of motion direction.}, Author = {Zheng, Ji-Jian and Lee, Seunghoon and Zhou, Z Jimmy}, Date-Added = {2013-04-01 15:21:15 +0000}, Date-Modified = {2013-08-15 13:00:54 +0000}, Doi = {10.1016/j.neuron.2004.11.015}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {retinal waves; Rabbits; spontaneous activity; Acetylcholine; retina; visual system; in vitro; calcium imaging; Patch-Clamp Techniques}, Mesh = {Acetylcholine; Aging; Animals; Electrophysiology; Embryo, Mammalian; Nerve Net; Nicotine; Patch-Clamp Techniques; Rabbits; Retina; Synapses; Vision, Ocular; gamma-Aminobutyric Acid}, Month = {Dec}, Number = {5}, Pages = {851-64}, pmid = {15572115}, Pst = {ppublish}, Title = {A developmental switch in the excitability and function of the starburst network in the mammalian retina}, Volume = {44}, Year = {2004}, url = {papers/Zheng_Neuron2004.pdf}} @article{Vanderhaeghen:2004, Abstract = {Roger Sperry proposed 40 years ago that topographic neural connections are established through complementary expression of chemoaffinity labels in projecting neurons and their final targets. This led to the identification of ephrins as key molecular cues controlling the topography of retinotectal projections. Recent studies have revealed a surprising twist to this model, shedding light on the developmental mechanisms patterning the projections between the thalamus and the cortex: ephrins, unexpectedly expressed in an intermediate target, control the establishment of topography of axonal projections between these two structures. The same cues are re-used later to control the mapping of thalamocortical projections within a given cortical area, which strikingly illustrates how a limited set of genes can contribute to generate several levels of complexity of a neuronal network.}, Author = {Vanderhaeghen, Pierre and Polleux, Franck}, Date-Added = {2013-04-01 15:19:28 +0000}, Date-Modified = {2017-05-05 21:54:52 +0000}, Doi = {10.1016/j.tins.2004.05.009}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {Research Support, Non-U.S. Gov't;Neurophysiology;Neural Pathways;Research Support, U.S. Gov't, P.H.S.;Animals;Thalamus;Cerebral Cortex;review;Humans}, Mesh = {Animals; Cerebral Cortex; Humans; Neural Pathways; Thalamus}, Month = {Jul}, Number = {7}, Pages = {384-91}, pmid = {15219737}, Pst = {ppublish}, Title = {Developmental mechanisms patterning thalamocortical projections: intrinsic, extrinsic and in between}, Volume = {27}, Year = {2004}, url = {papers/Vanderhaeghen_TrendsNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2004.05.009}} @article{Stahl:2004, Abstract = {Examining eye movements is an important part of the neurological evaluation of humans; the distribution of the neural circuits that control these movements is such that they are disrupted--often in highly characteristic fashions--by many disease processes. Technical advances have made it possible to measure accurately the eye movements of mice, so it is now possible to use the detective power of eye movement recording to characterize neurological dysfunction in genetically altered strains. Here we introduce analytical tools used in ocular motor research and demonstrate their ability to reveal disorders of the visual pathways, inner ear, and cerebellum.}, Author = {Stahl, John S}, Date-Added = {2013-04-01 15:15:48 +0000}, Date-Modified = {2017-10-27 18:23:27 +0000}, Doi = {10.1016/j.visres.2004.09.011}, Journal = {Vision Res}, Journal-Full = {Vision research}, Mesh = {Animals; Brain Diseases; Disease Models, Animal; Eye Movements; Mice; Mice, Neurologic Mutants; Nystagmus, Optokinetic; Psychomotor Performance; Reflex, Vestibulo-Ocular; Visual Pathways}, Month = {Dec}, Number = {28}, Pages = {3401-10}, pmid = {15536008}, Pst = {ppublish}, Title = {Using eye movements to assess brain function in mice}, Volume = {44}, Year = {2004}, url = {papers/Stahl_VisionRes2004.pdf}} @article{Charrier:2012, Abstract = {Structural genomic variations represent a major driving force of evolution, and a burst of large segmental gene duplications occurred in the human lineage during its separation from nonhuman primates. SRGAP2, a gene recently implicated in neocortical development, has undergone two human-specific duplications. Here, we find that both duplications (SRGAP2B and SRGAP2C) are partial and encode a truncated F-BAR domain. SRGAP2C is expressed in the developing and adult human brain and dimerizes with ancestral SRGAP2 to inhibit its function. In the mouse neocortex, SRGAP2 promotes spine maturation and limits spine density. Expression of SRGAP2C phenocopies SRGAP2 deficiency. It underlies sustained radial migration and leads to the emergence of human-specific features, including neoteny during spine maturation and increased density of longer spines. These results suggest that inhibition of SRGAP2 function by its human-specific paralogs has contributed to the evolution of the human neocortex and plays an important role during human brain development.}, Author = {Charrier, C{\'e}cile and Joshi, Kaumudi and Coutinho-Budd, Jaeda and Kim, Ji-Eun and Lambert, Nelle and de Marchena, Jacqueline and Jin, Wei-Lin and Vanderhaeghen, Pierre and Ghosh, Anirvan and Sassa, Takayuki and Polleux, Franck}, Date-Added = {2013-04-01 15:15:21 +0000}, Date-Modified = {2013-04-01 15:15:28 +0000}, Doi = {10.1016/j.cell.2012.03.034}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {downloads}, Mesh = {Animals; Brain; Cell Movement; Dendritic Spines; Evolution, Molecular; GTPase-Activating Proteins; Gene Duplication; Humans; Mice; Molecular Sequence Data; Neurons; Protein Structure, Tertiary; Segmental Duplications, Genomic; Species Specificity}, Month = {May}, Number = {4}, Pages = {923-35}, Pmc = {PMC3357949}, pmid = {22559944}, Pst = {ppublish}, Title = {Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation}, Volume = {149}, Year = {2012}, url = {papers/Charrier_Cell2012.pdf}} @article{Tamietto:2012, Abstract = {Nonconscious [1-6], rapid [7, 8], or coarse [9] visual processing of emotional stimuli induces functional activity in a subcortical pathway to the amygdala involving the superior colliculus and pulvinar. Despite evidence in lower mammals [10, 11] and nonhuman primates [12], it remains speculative whether anatomical connections between these structures exist in the human brain [13-15]. It is also unknown whether destruction of the visual cortex, which provides a major input to the amygdala, induces modifications in anatomical connections along this subcortical pathway. We used diffusion tensor imaging to investigate in vivo anatomical connections between human amygdala and subcortical visual structures in ten age-matched controls and in one patient with early unilateral destruction of the visual cortex. We found fiber connections between pulvinar and amygdala and also between superior colliculus and amygdala via the pulvinar in the controls as well as in the patient. Destruction of the visual cortex led to qualitative and quantitative modifications along the pathways connecting these three structures and the changes were confined to the patient's damaged hemisphere. The present findings thus show extensive neural plasticity in the anatomical connections between subcortical visual structures of old evolutionary origin involved in the processing of emotional stimuli.}, Author = {Tamietto, Marco and Pullens, Pim and de Gelder, Beatrice and Weiskrantz, Lawrence and Goebel, Rainer}, Date-Added = {2013-04-01 15:11:46 +0000}, Date-Modified = {2013-04-01 15:13:27 +0000}, Doi = {10.1016/j.cub.2012.06.006}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {downloads}, Mesh = {Amygdala; Brain Injuries; Case-Control Studies; Child; Diffusion Tensor Imaging; Humans; Male; Middle Aged; Superior Colliculi; Visual Cortex}, Month = {Aug}, Number = {15}, Pages = {1449-55}, pmid = {22748315}, Pst = {ppublish}, Title = {Subcortical connections to human amygdala and changes following destruction of the visual cortex}, Volume = {22}, Year = {2012}, url = {papers/Tamietto_CurrBiol2012.pdf}, Bdsk-File-2 = {papers/Tamietto_CurrBiol2012a.pdf}} @article{Hoshiko:2012, Abstract = {Accumulative evidence indicates that microglial cells influence the normal development of brain synapses. Yet, the mechanisms by which these immune cells target maturating synapses and influence their functional development at early postnatal stages remain poorly understood. Here, we analyzed the role of CX3CR1, a microglial receptor activated by the neuronal chemokine CX3CL1 (or fractalkine) which controls key functions of microglial cells. In the whisker-related barrel field of the mouse somatosensory cortex, we show that the recruitment of microglia to the sites where developing thalamocortical synapses are concentrated (i.e., the barrel centers) occurs only after postnatal day 5 and is controlled by the fractalkine/CX3CR1 signaling pathway. Indeed, at this developmental stage fractalkine is overexpressed within the barrels and CX3CR1 deficiency delays microglial cell recruitment into the barrel centers. Functional analysis of thalamocortical synapses shows that CX3CR1 deficiency also delays the functional maturation of postsynaptic glutamate receptors which normally occurs at these synapses between the first and second postnatal week. These results show that reciprocal interactions between neurons and microglial cells control the functional maturation of cortical synapses.}, Author = {Hoshiko, Maki and Arnoux, Isabelle and Avignone, Elena and Yamamoto, Nobuhiko and Audinat, Etienne}, Date-Added = {2013-03-19 14:24:43 +0000}, Date-Modified = {2013-03-19 14:25:58 +0000}, Doi = {10.1523/JNEUROSCI.1167-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; microglia; Thalamic Nuclei; Cerebral Cortex; Neocortex; barrels; Somatosensory Cortex}, Mesh = {Age Factors; Animals; Animals, Newborn; Chemokine CX3CL1; Developmental Disabilities; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Female; GABA Antagonists; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microglia; Receptors, Chemokine; Serotonin Plasma Membrane Transport Proteins; Somatosensory Cortex; Statistics, Nonparametric; Synapses; Thalamus}, Month = {Oct}, Number = {43}, Pages = {15106-11}, pmid = {23100431}, Pst = {ppublish}, Title = {Deficiency of the microglial receptor CX3CR1 impairs postnatal functional development of thalamocortical synapses in the barrel cortex}, Volume = {32}, Year = {2012}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1167-12.2012}} @article{Sato:2012a, Abstract = {The mammalian neocortex is composed of various types of neurons that reflect its laminar and area structures. It has been suggested that not only intrinsic but also afferent-derived extrinsic factors are involved in neuronal differentiation during development. However, the role and molecular mechanism of such extrinsic factors are almost unknown. Here, we attempted to identify molecules that are expressed in the thalamus and affect cortical cell development. First, thalamus-specific molecules were sought by comparing gene expression profiles of the developing rat thalamus and cortex using microarrays, and by constructing a thalamus-enriched subtraction cDNA library. A systematic screening by in situ hybridization showed that several genes encoding extracellular molecules were strongly expressed in sensory thalamic nuclei. Exogenous and endogenous protein localization further demonstrated that two extracellular molecules, Neuritin-1 (NRN1) and VGF, were transported to thalamic axon terminals. Application of NRN1 and VGF to dissociated cell culture promoted the dendritic growth. An organotypic slice culture experiment further showed that the number of primary dendrites in multipolar stellate neurons increased in response to NRN1 and VGF, whereas dendritic growth of pyramidal neurons was not promoted. These molecules also increased neuronal survival of multipolar neurons. Taken together, these results suggest that the thalamus-specific molecules NRN1 and VGF play an important role in the dendritic growth and survival of cortical neurons in a cell type-specific manner.}, Author = {Sato, Haruka and Fukutani, Yuma and Yamamoto, Yuji and Tatara, Eiichi and Takemoto, Makoto and Shimamura, Kenji and Yamamoto, Nobuhiko}, Date-Added = {2013-03-19 14:24:29 +0000}, Date-Modified = {2013-03-19 14:27:20 +0000}, Doi = {10.1523/JNEUROSCI.0293-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; rodent; rat; mouse; Visual Cortex; Somatosensory Cortex; thalamus; Gene Expression; Gene Expression Profiling; extrinsic; Growth Factor}, Mesh = {Animals; Antibodies, Blocking; Cell Survival; Cells, Cultured; Cerebral Cortex; DNA Primers; DNA, Complementary; Dendrites; Electroporation; Female; GPI-Linked Proteins; Genetic Vectors; Immunohistochemistry; In Situ Hybridization; Male; Microarray Analysis; Neurons; Neuropeptides; Plasmids; Pregnancy; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Thalamus; Transfection}, Month = {Oct}, Number = {44}, Pages = {15388-402}, pmid = {23115177}, Pst = {ppublish}, Title = {Thalamus-derived molecules promote survival and dendritic growth of developing cortical neurons}, Volume = {32}, Year = {2012}, url = {papers/Sato_JNeurosci2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0293-12.2012}} @article{Jin:2011, Abstract = {Reduced synaptic inhibition is an important factor contributing to posttraumatic epileptogenesis. Axonal sprouting and enhanced excitatory synaptic connectivity onto rodent layer V pyramidal (Pyr) neurons occur in epileptogenic partially isolated (undercut) neocortex. To determine if enhanced excitation also affects inhibitory circuits, we used laser scanning photostimulation of caged glutamate and whole-cell recordings from GAD67-GFP-expressing mouse fast spiking (FS) interneurons and Pyr cells in control and undercut in vitro slices to map excitatory and inhibitory synaptic inputs. Results are 1) the region-normalized excitatory postsynaptic current (EPSC) amplitudes and proportion of uncaging sites from which EPSCs could be evoked (hotspot ratio) "increased" significantly in FS cells of undercut slices; 2) in contrast, these parameters were significantly "decreased" for inhibitory postsynaptic currents (IPSCs) in undercut FS cells; and 3) in rat layer V Pyr neurons, we found significant decreases in IPSCs in undercut versus control Pyr neurons. The decreases were mainly located in layers II and IV, suggesting a reduction in the efficacy of interlaminar synaptic inhibition. Results suggest that there is significant synaptic reorganization in this model of posttraumatic epilepsy, resulting in increased excitatory drive and reduced inhibitory input to FS interneurons that should enhance their inhibitory output and, in part, offset similar alterations in innervation of Pyr cells.}, Author = {Jin, Xiaoming and Huguenard, John R and Prince, David A}, Date-Added = {2013-02-19 18:47:04 +0000}, Date-Modified = {2013-02-19 18:48:48 +0000}, Doi = {10.1093/cercor/bhq181}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {Epilepsy; inhibition; Development; neurophysiology; Interneurons; Pyramidal Cells; Neocortex; optical physiology; transgenic; mouse; mice; Patch-Clamp Techniques; Stimulation}, Mesh = {Animals; Brain Damage, Chronic; Disease Models, Animal; Epilepsy; Mice; Mice, Transgenic; Microscopy, Confocal; Neocortex; Neural Inhibition; Neural Pathways; Organ Culture Techniques; Photic Stimulation; Rats; Synaptic Transmission}, Month = {May}, Number = {5}, Pages = {1094-104}, Pmc = {PMC3077430}, pmid = {20855494}, Pst = {ppublish}, Title = {Reorganization of inhibitory synaptic circuits in rodent chronically injured epileptogenic neocortex}, Volume = {21}, Year = {2011}, url = {papers/Jin_CerebCortex2011.pdf}} @article{Tiriac:2012, Abstract = {Spontaneous activity in the sensory periphery drives infant brain activity and is thought to contribute to the formation of retinotopic and somatotopic maps. In infant rats during active (or REM) sleep, brainstem-generated spontaneous activity triggers hundreds of thousands of skeletal muscle twitches each day; sensory feedback from the resulting limb movements is a primary activator of forebrain activity. The rodent whisker system, with its precise isomorphic mapping of individual whiskers to discrete brain areas, has been a key contributor to our understanding of somatotopic maps and developmental plasticity. But although whisker movements are controlled by dedicated skeletal muscles, spontaneous whisker activity has not been entertained as a contributing factor to the development of this system. Here we report in 3- to 6-day-old rats that whiskers twitch rapidly and asynchronously during active sleep; furthermore, neurons in whisker thalamus exhibit bursts of activity that are tightly associated with twitches but occur infrequently during waking. Finally, we observed barrel-specific cortical activity during periods of twitching. This is the first report of self-generated, sleep-related twitches in the developing whisker system, a sensorimotor system that is unique for the precision with which it can be experimentally manipulated. The discovery of whisker twitching will allow us to attain a better understanding of the contributions of peripheral sensory activity to somatosensory integration and plasticity in the developing nervous system.}, Author = {Tiriac, Alexandre and Uitermarkt, Brandt D and Fanning, Alexander S and Sokoloff, Greta and Blumberg, Mark S}, Date-Added = {2013-02-19 18:45:31 +0000}, Date-Modified = {2013-02-19 18:46:22 +0000}, Doi = {10.1016/j.cub.2012.09.009}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {Somatosensory Cortex; topographic map; development; sensory-motor; barrels; Neocortex; Rats}, Month = {Nov}, Number = {21}, Pages = {2075-80}, Pmc = {PMC3494768}, pmid = {23084988}, Pst = {ppublish}, Title = {Rapid whisker movements in sleeping newborn rats}, Volume = {22}, Year = {2012}, url = {papers/Tiriac_CurrBiol2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2012.09.009}} @article{Chen:2012, Abstract = {The ability to chronically monitor neuronal activity in the living brain is essential for understanding the organization and function of the nervous system. The genetically encoded green fluorescent protein-based calcium sensor GCaMP provides a powerful tool for detecting calcium transients in neuronal somata, processes, and synapses that are triggered by neuronal activities. Here we report the generation and characterization of transgenic mice that express improved GCaMPs in various neuronal subpopulations under the control of the Thy1 promoter. In vitro and in vivo studies show that calcium transients induced by spontaneous and stimulus-evoked neuronal activities can be readily detected at the level of individual cells and synapses in acute brain slices, as well as chronically in awake, behaving animals. These GCaMP transgenic mice allow investigation of activity patterns in defined neuronal populations in the living brain and will greatly facilitate dissecting complex structural and functional relationships of neural networks.}, Author = {Chen, Qian and Cichon, Joseph and Wang, Wenting and Qiu, Li and Lee, Seok-Jin R and Campbell, Nolan R and Destefino, Nicholas and Goard, Michael J and Fu, Zhanyan and Yasuda, Ryohei and Looger, Loren L and Arenkiel, Benjamin R and Gan, Wen-Biao and Feng, Guoping}, Date-Added = {2013-02-19 18:43:41 +0000}, Date-Modified = {2013-02-19 18:44:39 +0000}, Doi = {10.1016/j.neuron.2012.07.011}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {in vivo; mouse; mice; transgenic; Transgenes; calcium sensor; calcium imaging; optical physiology; technique}, Mesh = {Age Factors; Animals; Antigens, Thy-1; Biophysics; Brain; Calcium; Calmodulin; Cell Count; Cell Line, Transformed; Dendrites; Dose-Response Relationship, Drug; Electric Stimulation; Gene Expression Regulation; Green Fluorescent Proteins; Humans; Membrane Potentials; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Mutation; Myosin-Light-Chain Kinase; Neurons; Odors; Patch-Clamp Techniques; Peptide Fragments; Potassium Chloride; Retina; Transfection}, Month = {Oct}, Number = {2}, Pages = {297-308}, pmid = {23083733}, Pst = {ppublish}, Title = {Imaging neural activity using Thy1-GCaMP transgenic mice}, Volume = {76}, Year = {2012}, url = {papers/Chen_Neuron2012.pdf}, Bdsk-File-2 = {papers/Chen_Neuron2012a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.07.011}} @article{Vogel:2010, Abstract = {A full understanding of the development of the brain's functional network architecture requires not only an understanding of developmental changes in neural processing in individual brain regions but also an understanding of changes in inter-regional interactions. Resting state functional connectivity MRI (rs-fcMRI) is increasingly being used to study functional interactions between brain regions in both adults and children. We briefly review methods used to study functional interactions and networks with rs-fcMRI and how these methods have been used to define developmental changes in network functional connectivity. The developmental rs-fcMRI studies to date have found two general properties. First, regional interactions change from being predominately anatomically local in children to interactions spanning longer cortical distances in young adults. Second, this developmental change in functional connectivity occurs, in general, via mechanisms of segregation of local regions and integration of distant regions into disparate subnetworks.}, Author = {Vogel, Alecia C and Power, Jonathan D and Petersen, Steven E and Schlaggar, Bradley L}, Date-Added = {2013-01-29 20:46:29 +0000}, Date-Modified = {2013-01-29 20:47:02 +0000}, Doi = {10.1007/s11065-010-9145-7}, Journal = {Neuropsychol Rev}, Journal-Full = {Neuropsychology review}, Keywords = {toread; default mode network; resting state; development; fMRI; connectivity}, Mesh = {Age Factors; Brain; Brain Mapping; Functional Laterality; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Nerve Net; Neural Pathways; Neurons; Oxygen; Synapses}, Month = {Dec}, Number = {4}, Pages = {362-75}, pmid = {20976563}, Pst = {ppublish}, Title = {Development of the brain's functional network architecture}, Volume = {20}, Year = {2010}, url = {papers/Vogel_NeuropsycholRev2010.pdf}} @article{Donoghue:1999, Abstract = {To identify molecules that may play a role in the initiation of cerebral cortical area formation, we examined the expression of the Eph receptors and their ligands, the ephrins, during primate corticogenesis. We selected the macaque monkey neocortex because of its clear areal subdivisions, large surface area, protracted development (gestation = 165 d), and similarity to the human brain. In situ hybridizations, performed at early [embryonic day 65 (E65)], middle (E80), and late (E95) stages of cortical development, revealed that EphA system family members are expressed in distinct gradients and laminar and areal domains in the embryonic neocortex. Indeed, several regionally restricted molecular patterns are already apparent within the cortical plate at E65, before the formation of thalamocortical connections, suggesting that the initial expression of some EphA system members is regulated by programs intrinsic to cortical cells. For example, EphA3, EphA6, and EphA7 are all selectively expressed within the presumptive visual cortex. However, although EphA6 and EphA7 are present throughout this region, EphA3 is only expressed in the prospective extrastriate cortex, suggesting that cortical cells harbor functional biases that may influence the formation of appropriate synaptic connections. Although several patterns of early gene expression are stable (e.g., EphA3, EphA4, and EphA6), others change as development proceeds (e.g., EphA5, EphA7, ephrin-A2, ephrin-A3, and ephrin-A5), perhaps responding to extrinsic cues. Thus, at E95, after connections between the cortical plate and thalamus have formed, receptor subtypes EphA3, EphA5, EphA6, and EphA7 and the ligand ephrin-A5 are expressed in posterior regions, whereas EphA4 and ephrin-A2 and ephrin-A3 are either uniformly distributed or anteriorly biased. Taken together, our results demonstrate molecular distinctions among cells of the embryonic primate neocortex, revealing hitherto unrecognized compartmentalization early in corticogenesis.}, Author = {Donoghue, M J and Rakic, P}, Date-Added = {2013-01-29 20:45:59 +0000}, Date-Modified = {2013-01-29 20:45:59 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Cerebral Cortex; Embryonic and Fetal Development; Gene Expression Regulation, Developmental; Gestational Age; Humans; In Situ Hybridization; Macaca mulatta; Nerve Tissue Proteins; Organ Specificity; Receptor Protein-Tyrosine Kinases}, Month = {Jul}, Number = {14}, Pages = {5967-79}, pmid = {10407035}, Pst = {ppublish}, Title = {Molecular evidence for the early specification of presumptive functional domains in the embryonic primate cerebral cortex}, Volume = {19}, Year = {1999}, url = {papers/Donoghue_JNeurosci1999.pdf}} @article{Lu:2012, Abstract = {The default mode network (DMN) in humans has been suggested to support a variety of cognitive functions and has been implicated in an array of neuropsychological disorders. However, its function(s) remains poorly understood. We show that rats possess a DMN that is broadly similar to the DMNs of nonhuman primates and humans. Our data suggest that, despite the distinct evolutionary paths between rodent and primate brain, a well-organized, intrinsically coherent DMN appears to be a fundamental feature in the mammalian brain whose primary functions might be to integrate multimodal sensory and affective information to guide behavior in anticipation of changing environmental contingencies.}, Author = {Lu, Hanbing and Zou, Qihong and Gu, Hong and Raichle, Marcus E and Stein, Elliot A and Yang, Yihong}, Date-Added = {2013-01-29 20:26:54 +0000}, Date-Modified = {2013-04-23 17:55:27 +0000}, Doi = {10.1073/pnas.1200506109}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {default mode network; resting state; connectivity; wholeBrain; toread; grants; cerebral cortex; mirror symmetry; neocortex; cerebral cortex; areas; parcellation; patterning; topographic map; cytoarchitectonics}, Mesh = {Animals; Behavior, Animal; Brain; Brain Mapping; Haplorhini; Humans; Magnetic Resonance Imaging; Models, Anatomic; Models, Biological; Neural Pathways; Rats; Species Specificity}, Month = {Mar}, Number = {10}, Pages = {3979-84}, Pmc = {PMC3309754}, pmid = {22355129}, Pst = {ppublish}, Title = {Rat brains also have a default mode network}, Volume = {109}, Year = {2012}, url = {papers/Lu_ProcNatlAcadSciUSA2012.pdf}, Bdsk-File-2 = {papers/Lu_ProcNatlAcadSciUSA2012a.pdf}} @article{Kron:2012, Abstract = {Excitatory-inhibitory imbalance has been identified within specific brain microcircuits in models of Rett syndrome (RTT) and other autism spectrum disorders (ASDs). However, macrocircuit dysfunction across the RTT brain as a whole has not been defined. To approach this issue, we mapped expression of the activity-dependent, immediate-early gene product Fos in the brains of wild-type (Wt) and methyl-CpG-binding protein 2 (Mecp2)-null (Null) mice, a model of RTT, before and after the appearance of overt symptoms (3 and 6 weeks of age, respectively). At 6 weeks, Null mice exhibit significantly less Fos labeling than Wt in limbic cortices and subcortical structures, including key nodes in the default mode network. In contrast, Null mice exhibit significantly more Fos labeling than Wt in the hindbrain, most notably in cardiorespiratory regions of the nucleus tractus solitarius (nTS). Using nTS as a model, whole-cell recordings demonstrated that increased Fos expression in Nulls at 6 weeks of age is associated with synaptic hyperexcitability, including increased frequency of spontaneous and miniature EPSCs and increased amplitude of evoked EPSCs in Nulls. No such effect of genotype on Fos or synaptic function was seen at 3 weeks. In the mutant forebrain, reduced Fos expression, as well as abnormal sensorimotor function, were reversed by the NMDA receptor antagonist ketamine. In light of recent findings that the default mode network is hypoactive in autism, our data raise the possibility that hypofunction within this meta-circuit is a shared feature of RTT and other ASDs and is reversible.}, Author = {Kron, Miriam and Howell, C James and Adams, Ian T and Ransbottom, Michael and Christian, Diana and Ogier, Michael and Katz, David M}, Date-Added = {2013-01-29 20:22:24 +0000}, Date-Modified = {2013-01-29 20:22:57 +0000}, Doi = {10.1523/JNEUROSCI.2159-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Immediate-Early; gene; default mode network; resting state; Autistic Disorder; autism; Rett Syndrome;}, Mesh = {Animals; Autonomic Nervous System; Cerebellum; Disease Models, Animal; Excitatory Amino Acid Antagonists; Female; Gene Expression Regulation, Developmental; Genes, fos; Humans; Ketamine; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Knockout; Miniature Postsynaptic Potentials; Nerve Net; Nerve Tissue Proteins; Organ Specificity; Patch-Clamp Techniques; Prosencephalon; Proto-Oncogene Proteins c-fos; Rett Syndrome; Sensory Gating; Solitary Nucleus; Synaptic Transmission}, Month = {Oct}, Number = {40}, Pages = {13860-72}, Pmc = {PMC3500840}, pmid = {23035095}, Pst = {ppublish}, Title = {Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment}, Volume = {32}, Year = {2012}, url = {papers/Kron_JNeurosci2012.pdf}} @article{White:2012, Abstract = {Resting-state networks derived from temporal correlations of spontaneous hemodynamic fluctuations have been extensively used to elucidate the functional organization of the brain in adults and infants. We have previously developed functional connectivity diffuse optical tomography methods in adults, and we now apply these techniques to study functional connectivity in newborn infants at the bedside. We present functional connectivity maps in the occipital cortices obtained from healthy term-born infants and premature infants, including one infant with an occipital stroke. Our results suggest that functional connectivity diffuse optical tomography has potential as a valuable clinical tool for the early detection of functional deficits and for providing prognostic information on future development.}, Author = {White, Brian R and Liao, Steve M and Ferradal, Silvina L and Inder, Terrie E and Culver, Joseph P}, Date-Added = {2013-01-29 20:19:43 +0000}, Date-Modified = {2013-01-29 20:20:20 +0000}, Doi = {10.1016/j.neuroimage.2011.08.094}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Keywords = {default mode network; resting state; human; neonatal; fetal; optical imaging; visual cortex; connectivity}, Mesh = {Brain Injuries; Brain Mapping; Cerebrovascular Circulation; Data Interpretation, Statistical; Diagnostic Imaging; Electroencephalography; Feasibility Studies; Female; Functional Laterality; Humans; Image Processing, Computer-Assisted; Infant, Newborn; Infant, Premature; Male; Models, Anatomic; Neural Pathways; Occipital Lobe; Pilot Projects; Point-of-Care Systems; Prognosis; Stroke; Tomography; Visual Cortex}, Month = {Feb}, Number = {3}, Pages = {2529-38}, pmid = {21925609}, Pst = {ppublish}, Title = {Bedside optical imaging of occipital resting-state functional connectivity in neonates}, Volume = {59}, Year = {2012}, url = {papers/White_Neuroimage2012.pdf}} @article{White:2011, Abstract = {Functional neuroimaging (e.g., with fMRI) has been difficult to perform in mice, making it challenging to translate between human fMRI studies and molecular and genetic mechanisms. A method to easily perform large-scale functional neuroimaging in mice would enable the discovery of functional correlates of genetic manipulations and bridge with mouse models of disease. To satisfy this need, we combined resting-state functional connectivity mapping with optical intrinsic signal imaging (fcOIS). We demonstrate functional connectivity in mice through highly detailed fcOIS mapping of resting-state networks across most of the cerebral cortex. Synthesis of multiple network connectivity patterns through iterative parcellation and clustering provides a comprehensive map of the functional neuroarchitecture and demonstrates identification of the major functional regions of the mouse cerebral cortex. The method relies on simple and relatively inexpensive camera-based equipment, does not require exogenous contrast agents and involves only reflection of the scalp (the skull remains intact) making it minimally invasive. In principle, fcOIS allows new paradigms linking human neuroscience with the power of molecular/genetic manipulations in mouse models.}, Author = {White, Brian R and Bauer, Adam Q and Snyder, Abraham Z and Schlaggar, Bradley L and Lee, Jin-Moo and Culver, Joseph P}, Date-Added = {2013-01-29 20:03:54 +0000}, Date-Modified = {2013-01-29 20:13:03 +0000}, Doi = {10.1371/journal.pone.0016322}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {toread; technique; grants; wholeBrain; default mode network; resting state; spontaneous activity; mouse; mice; fMRI; Cerebral Cortex; mirror symmetry}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Equipment Design; Magnetic Resonance Imaging; Methods; Mice; Neural Pathways; Optical Devices}, Number = {1}, Pages = {e16322}, Pmc = {PMC3024435}, pmid = {21283729}, Pst = {epublish}, Title = {Imaging of functional connectivity in the mouse brain}, Volume = {6}, Year = {2011}, url = {papers/White_PLoSOne2011.pdf}, Bdsk-File-2 = {papers/White_PLoSOne2011.eps}, Bdsk-File-3 = {papers/White_PLoSOne2011a.eps}, Bdsk-File-4 = {papers/White_PLoSOne2011b.eps}, Bdsk-File-5 = {papers/White_PLoSOne2011c.eps}, Bdsk-File-6 = {papers/White_PLoSOne2011e.eps}, Bdsk-File-7 = {papers/White_PLoSOne2011d.eps}} @article{Denenberg:1991c, Abstract = {We have recently developed a computer program for measuring midsagittal sections of the human corpus callosum, similar to one used for the rat. Callosal area, perimeter, axis length, and 99 widths for 104 subjects were entered into a factor analysis in order to define regional clusters. Seven width factors were obtained. Regional widths were found to be sensitive to Sex X Handedness interactions in the anterior body, with right-handed females and left-handed males being larger. In the posterior body males had wider callosa than females. A further analysis within the 'isthmus' region compared consistent and non-consistent right-handed males and females. Consistent right-handed males and both female groups had smaller callosa than non-consistent right-handed males. These findings confirmed the use of consistency of handedness as an important independent variable with respect to human callosal morphology.}, Author = {Denenberg, V H and Kertesz, A and Cowell, P E}, Date-Added = {2013-01-29 16:45:35 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {Cerebral Cortex; hemisphere; asymmetry; lateralization; Grants; forelimb}, Mesh = {Adult; Animals; Brain Mapping; Corpus Callosum; Female; Functional Laterality; Haplorhini; Humans; Male; Sex Characteristics}, Month = {May}, Number = {1-2}, Pages = {126-32}, pmid = {1907877}, Pst = {ppublish}, Title = {A factor analysis of the human's corpus callosum}, Volume = {548}, Year = {1991}} @article{Denenberg:1991b, Abstract = {As an animal swims through the Lashley III maze, an observer types into a Macintosh computer the path taken. The computer program, Observe Software, then breaks the string of choices into two-step sequences and counts the number of such sequences. These data are then sent to a spreadsheet, where the sequences are sorted into forward and backward responses. Forward choices are Correct Path, T Choice Errors and Cul Entry Errors. All backward choices are errors, by definition. They are classified as T Choices, Cul Entries, Cul Exits, and Return to Start. The animal's behavior is then described by the various error classes plus a measure called Learning Index. Examples of learning by rats and mice are presented.}, Author = {Denenberg, V H and Talgo, N and Carroll, D A and Freter, S and Deni, R}, Date-Added = {2013-01-29 16:45:09 +0000}, Date-Modified = {2013-01-29 16:45:09 +0000}, Journal = {Physiol Behav}, Journal-Full = {Physiology \& behavior}, Mesh = {Animals; Escape Reaction; Image Processing, Computer-Assisted; Mental Recall; Mice; Mice, Inbred Strains; Microcomputers; Orientation; Problem Solving; Rats; Rats, Inbred Strains; Software}, Month = {Oct}, Number = {4}, Pages = {857-61}, pmid = {1775564}, Pst = {ppublish}, Title = {A computer-aided procedure for measuring Lashley III maze performance}, Volume = {50}, Year = {1991}} @article{Denenberg:1991a, Abstract = {Previous research found that the corpus callosum of male rats is larger than that of females; handling rats in infancy enhances this sex difference; and female rat pups, when handled in infancy and given 1 injection of testosterone propionate (TP) on Day 4 of life, will have callosa as large as those of males. In 2 experiments, male pups were castrated on Day 1 or received sham surgery; female pups were injected with TP on Day 4 or received an oil injection. Litters were handled or nonhandled. The previous finding that females, when handled and given TP in infancy, have a larger callosum was confirmed; however, a TP effect when administered to nonhandled females was not found. Because handling is known to cause a corticosterone release, these findings were interpreted as evidence of a developmental interaction between adrenal and gonadal hormones at the cortical level.}, Author = {Denenberg, V H and Fitch, R H and Schrott, L M and Cowell, P E and Waters, N S}, Date-Added = {2013-01-29 16:43:01 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Journal = {Behav Neurosci}, Journal-Full = {Behavioral neuroscience}, Keywords = {Cerebral Cortex; hemisphere; asymmetry; lateralization; Grants; forelimb}, Mesh = {Animals; Animals, Newborn; Arousal; Brain Mapping; Cerebral Cortex; Corpus Callosum; Female; Handling (Psychology); Male; Pregnancy; Rats; Rats, Inbred Strains; Sex Differentiation; Testosterone}, Month = {Aug}, Number = {4}, Pages = {562-6}, pmid = {1930724}, Pst = {ppublish}, Title = {Corpus callosum: interactive effects of infantile handling and testosterone in the rat}, Volume = {105}, Year = {1991}} @article{Denenberg:1991, Abstract = {NZB and BXSB mice were given a battery of behavioral tests including paw preference, water escape, Lashley III maze, and discrimination learning. Their brains were then evaluated for cortical ectopias. The incidence of ectopias was 40.5% in NZBs and 48.5% in BXSBs. In the NZB strain left-pawed ectopic mice (both male and female) had the fastest swimming time in the water escape test, while right-pawed ectopics were the slowest. The same findings were obtained for left- and right-pawed ectopic BXSB males, but not for the females. However, on discrimination learning the BXSB males had the exact opposite pattern: right-pawed ectopics were the best learners while left-pawed ectopics were the worst. Male BXSBs and both male and female NZBs were manifesting autoimmune disease at the time of testing, while female BXSBs were not, suggesting that autoimmunity is a necessary background condition for the differential expression of ectopias and paw preference upon learning processes. The finding that the left-pawed ectopic BXSB mice, who were the poorest learners in the non-spatial discrimination learning test, learned best in the spatial water escape test is in agreement with the Geschwind hypothesis that pathological events during brain development may, in some instances, produce superiority of function.}, Author = {Denenberg, V H and Sherman, G F and Schrott, L M and Rosen, G D and Galaburda, A M}, Date-Added = {2013-01-29 16:42:59 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {Cerebral Cortex; hemisphere; asymmetry; lateralization; Grants; forelimb}, Mesh = {Animals; Autoimmune Diseases; Brain; Cerebral Cortex; Discrimination (Psychology); Escape Reaction; Functional Laterality; Learning; Mice; Mice, Inbred Strains; Space Perception}, Month = {Oct}, Number = {1}, Pages = {98-104}, pmid = {1799876}, Pst = {ppublish}, Title = {Spatial learning, discrimination learning, paw preference and neocortical ectopias in two autoimmune strains of mice}, Volume = {562}, Year = {1991}, url = {papers/Denenberg_BrainRes1991.pdf}} @article{Waters:1991, Abstract = {A lateral paw preference testing unit is described. Mice are allowed access to preferred food with either their left or right forepaw, and the amount eaten with each paw is measured. The unit allows easy measurement and quantification of this behavior, without requiring food deprivation or continuous monitoring of the subjects, and may be performed in the subject's home cage. Its reliability under a number of conditions is reported. The results do not correlate with those obtained using the Collins paw preference test.}, Author = {Waters, N S and Denenberg, V H}, Date-Added = {2013-01-29 16:41:46 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Journal = {Physiol Behav}, Journal-Full = {Physiology \& behavior}, Keywords = {Cerebral Cortex; hemisphere; asymmetry; lateralization; Grants; forelimb}, Mesh = {Animals; Appetitive Behavior; Dominance, Cerebral; Mice; Psychomotor Performance; Social Environment}, Month = {Oct}, Number = {4}, Pages = {853-6}, pmid = {1775563}, Pst = {ppublish}, Title = {A measure of lateral paw preference in the mouse}, Volume = {50}, Year = {1991}, url = {papers/Waters_PhysiolBehav1991.pdf}} @article{Vyazovskiy:2008a, Abstract = {Sleep electroencephalographic (EEG) slow-wave activity is increased after wakefulness and decreases during sleep. Regional sleep EEG differences are thought to be a consequence of activation of specific cortical neuronal circuits during waking. We investigated the relationship between handedness and interhemispheric brain asymmetry. Bilateral EEG recordings were obtained from the frontal and occipital cortex in rats with a clear paw preference in a food-reaching task (right, n = 5; left, n = 5). While still na{\"\i}ve to the task, no waking or sleep EEG asymmetry was present. During the food-reaching task, the waking EEG showed significant, substantial power increases in the frontal hemisphere contralateral to the dominant paw in the low theta range (4.5-6.0 Hz). Moreover, the non-REM sleep EEG following feeding bouts was markedly asymmetric, with significantly higher power in the hemisphere contralateral to the preferred paw in frequencies >1.5 Hz. No asymmetry was evident in the occipital EEG. Correlation analyses revealed a positive association between the hemispheric asymmetry during sleep and the degree of preferred use of the contralateral paw during waking in frequencies <9.0 Hz. Our findings show that handedness is reflected in specific, regional EEG asymmetry during sleep. Neuronal activity induced by preferential use of a particular forelimb led to a local enhancement of EEG power in frequencies within the delta and sigma ranges, supporting the hypothesis of use-dependent local sleep regulation. We conclude that inherent laterality is manifested when animals are exposed to complex behavioral tasks, and sleep plays a role in consolidating the hemispheric dominance of the brain.}, Author = {Vyazovskiy, V V and Tobler, I}, Date-Added = {2013-01-29 16:36:04 +0000}, Date-Modified = {2013-09-25 12:31:24 +0000}, Doi = {10.1152/jn.01154.2007}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {asymmetry; symmetry; EEG; neurophysiology; sleep; in vivo; rats; Frontal; visual cortex; Cerebral Cortex; asymmetry; hemipshere; Grants; forelimb}, Mesh = {Animals; Behavior, Animal; Electroencephalography; Functional Laterality; Male; Occipital Lobe; Rats; Rats, Sprague-Dawley; Sleep; Sleep Deprivation; Wakefulness}, Month = {Feb}, Number = {2}, Pages = {969-75}, pmid = {18077659}, Pst = {ppublish}, Title = {Handedness leads to interhemispheric EEG asymmetry during sleep in the rat}, Volume = {99}, Year = {2008}, url = {papers/Vyazovskiy_JNeurophysiol2008.pdf}} @article{Dharmaratne:2012, Abstract = {BACKGROUND: The alignment of ipsilaterally and contralaterally projecting retinal axons that view the same part of visual space is fundamental to binocular vision. While much progress has been made regarding the mechanisms which regulate contralateral topography, very little is known of the mechanisms which regulate the mapping of ipsilateral axons such that they align with their contralateral counterparts. RESULTS: Using the advantageous model provided by the mouse retinocollicular pathway, we have performed anterograde tracing experiments which demonstrate that ipsilateral retinal axons begin to form terminal zones (TZs) in the superior colliculus (SC), within the first few postnatal days. These appear mature by postnatal day 11. Importantly, TZs formed by ipsilaterally-projecting retinal axons are spatially offset from those of contralaterally-projecting axons arising from the same retinotopic location from the outset. This pattern is consistent with that required for adult visuotopy. We further demonstrate that a member of the Ten-m/Odz/Teneurin family of homophilic transmembrane glycoproteins, Ten-m3, is an essential regulator of ipsilateral retinocollicular topography. Ten-m3 mRNA is expressed in a high-medial to low-lateral gradient in the developing SC. This corresponds topographically with its high-ventral to low-dorsal retinal gradient. In Ten-m3 knockout mice, contralateral ventrotemporal axons appropriately target rostromedial SC, whereas ipsilateral axons exhibit dramatic targeting errors along both the mediolateral and rostrocaudal axes of the SC, with a caudal shift of the primary TZ, as well as the formation of secondary, caudolaterally displaced TZs. In addition to these dramatic ipsilateral-specific mapping errors, both contralateral and ipsilateral retinocollicular TZs exhibit more subtle changes in morphology. CONCLUSIONS: We conclude that important aspects of adult visuotopy are established via the differential sensitivity of ipsilateral and contralateral axons to intrinsic guidance cues. Further, we show that Ten-m3 plays a critical role in this process and is particularly important for the mapping of the ipsilateral retinocollicular pathway.}, Author = {Dharmaratne, Nuwan and Glendining, Kelly A and Young, Timothy R and Tran, Heidi and Sawatari, Atomu and Leamey, Catherine A}, Date-Added = {2013-01-29 15:24:47 +0000}, Date-Modified = {2013-01-29 15:25:24 +0000}, Doi = {10.1371/journal.pone.0043083}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {retinotopy; topographic map; Superior Colliculus; optic tectum; mice; mouse; gene; ipsilateral}, Number = {9}, Pages = {e43083}, Pmc = {PMC3446960}, pmid = {23028443}, Pst = {ppublish}, Title = {Ten-m3 is required for the development of topography in the ipsilateral retinocollicular pathway}, Volume = {7}, Year = {2012}, url = {papers/Dharmaratne_PLoSOne2012.pdf}} @article{Wyatt:2012, Abstract = {The stability of dendritic spines in the neocortex is profoundly influenced by sensory experience, which determines the magnitude and pattern of neural firing. By optically manipulating the temporal structure of neural activity in vivo using channelrhodopsin-2 and repeatedly imaging dendritic spines along these stimulated neurons over a period of weeks, we show that the specific pattern, rather than the total amount of activity, determines spine stability in awake mice.}, Author = {Wyatt, Ryan M and Tring, Elaine and Trachtenberg, Joshua T}, Date-Added = {2013-01-29 15:22:06 +0000}, Date-Modified = {2013-01-29 15:22:57 +0000}, Doi = {10.1038/nn.3134}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Dendrites; spines; neural activity; optogenetics}, Mesh = {Action Potentials; Amygdala; Animals; Dendritic Spines; Mice; Mice, Transgenic; Neocortex; Neural Pathways; Rhodopsin; Sensory Receptor Cells; Wakefulness}, Month = {Jul}, Number = {7}, Pages = {949-51}, Pmc = {PMC3386353}, pmid = {22706266}, Pst = {epublish}, Title = {Pattern and not magnitude of neural activity determines dendritic spine stability in awake mice}, Volume = {15}, Year = {2012}, url = {papers/Wyatt_NatNeurosci2012.pdf}} @article{Feldheim:1998, Abstract = {Visual connections to the mammalian forebrain are known to be patterned by neural activity, but it remains unknown whether the map topography of such higher sensory projections depends on axon guidance labels. Here, we show complementary expression and binding for the receptor EphA5 in mouse retina and its ligands ephrin-A2 and ephrin-A5 in multiple retinal targets, including the major forebrain target, the dorsal lateral geniculate nucleus (dLGN). These ligands can act in vitro as topographically specific repellents for mammalian retinal axons and are necessary for normal dLGN mapping in vivo. The results suggest a general and economic modular mechanism for brain mapping whereby a projecting field is mapped onto multiple targets by repeated use of the same labels. They also indicate the nature of a coordinate system for the mapping of sensory connections to the forebrain.}, Author = {Feldheim, D A and Vanderhaeghen, P and Hansen, M J and Fris{\'e}n, J and Lu, Q and Barbacid, M and Flanagan, J G}, Date-Added = {2013-01-29 15:13:39 +0000}, Date-Modified = {2013-01-29 15:14:58 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Ephrins; retina; optic tectum; Superior Colliculus; topographic map; retinotopy; Gene Expression; gradients; genetic; axon guidance}, Mesh = {Aging; Animals; Axons; Brain Mapping; Embryo, Mammalian; Ephrin-A2; Ephrin-A5; Gene Expression Regulation, Developmental; Geniculate Bodies; Membrane Proteins; Mice; Polymerase Chain Reaction; Prosencephalon; Receptor Protein-Tyrosine Kinases; Receptor, EphA5; Retina; Transcription Factors; Visual Pathways}, Month = {Dec}, Number = {6}, Pages = {1303-13}, pmid = {9883724}, Pst = {ppublish}, Title = {Topographic guidance labels in a sensory projection to the forebrain}, Volume = {21}, Year = {1998}, url = {papers/Feldheim_Neuron1998.pdf}} @article{Chang:2012, Abstract = {Social decisions are crucial for the success of individuals and the groups that they comprise. Group members respond vicariously to benefits obtained by others, and impairments in this capacity contribute to neuropsychiatric disorders such as autism and sociopathy. We examined the manner in which neurons in three frontal cortical areas encoded the outcomes of social decisions as monkeys performed a reward-allocation task. Neurons in the orbitofrontal cortex (OFC) predominantly encoded rewards that were delivered to oneself. Neurons in the anterior cingulate gyrus (ACCg) encoded reward allocations to the other monkey, to oneself or to both. Neurons in the anterior cingulate sulcus (ACCs) signaled reward allocations to the other monkey or to no one. In this network of received (OFC) and foregone (ACCs) reward signaling, ACCg emerged as an important nexus for the computation of shared experience and social reward. Individual and species-specific variations in social decision-making might result from the relative activation and influence of these areas.}, Author = {Chang, Steve W C and Gari{\'e}py, Jean-Fran{\c c}ois and Platt, Michael L}, Date-Added = {2013-01-29 14:56:31 +0000}, Date-Modified = {2013-01-29 14:58:20 +0000}, Doi = {10.1038/nn.3287}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {monkey; Social Behavior; reward; Cognition; orbitofrontal; Cerebral Cortex; Neocortex; mirror neuron; cingulate; Frontal Lobe; empathy}, Month = {Dec}, Number = {2}, Pages = {243-50}, pmid = {23263442}, Pst = {ppublish}, Title = {Neuronal reference frames for social decisions in primate frontal cortex}, Volume = {16}, Year = {2012}, url = {papers/Chang_NatNeurosci2012.pdf}} @article{Buckner:2008, Abstract = {Thirty years of brain imaging research has converged to define the brain's default network-a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.}, Author = {Buckner, Randy L and Andrews-Hanna, Jessica R and Schacter, Daniel L}, Date-Added = {2013-01-29 14:53:12 +0000}, Date-Modified = {2013-01-29 14:55:37 +0000}, Doi = {10.1196/annals.1440.011}, Journal = {Ann N Y Acad Sci}, Journal-Full = {Annals of the New York Academy of Sciences}, Keywords = {grants; default mode network; resting state; fMRI; cognition; cingulate; monkey; empathy}, Mesh = {Animals; Brain; Brain Diseases; Brain Mapping; Humans; Models, Neurological; Nerve Net}, Month = {Mar}, Pages = {1-38}, pmid = {18400922}, Pst = {ppublish}, Title = {The brain's default network: anatomy, function, and relevance to disease}, Volume = {1124}, Year = {2008}, url = {papers/Buckner_AnnNYAcadSci2008.pdf}} @article{Sommer:2004, Abstract = {Neuronal processing in cerebral cortex and signal transmission from cortex to brain stem have been studied extensively, but little is known about the numerous feedback pathways that ascend from brain stem to cortex. In this study, we characterized the signals conveyed through an ascending pathway coursing from the superior colliculus (SC) to the frontal eye field (FEF) via mediodorsal thalamus (MD). Using antidromic and orthodromic stimulation, we identified SC source neurons, MD relay neurons, and FEF recipient neurons of the pathway in Macaca mulatta. The monkeys performed oculomotor tasks, including delayed-saccade tasks, that permitted analysis of signals such as visual activity, delay activity, and presaccadic activity. We found that the SC sends all of these signals into the pathway with no output selectivity, i.e., the signals leaving the SC resembled those found generally within the SC. Visual activity arrived in FEF too late to contribute to short-latency visual responses there, and delay activity was largely filtered out in MD. Presaccadic activity, however, seemed critical because it traveled essentially unchanged from SC to FEF. Signal transmission in the pathway was fast ( approximately 2 ms from SC to FEF) and topographically organized (SC neurons drove MD and FEF neurons having similarly eccentric visual and movement fields). Our analysis of identified neurons in one pathway from brain stem to frontal cortex thus demonstrates that multiple signals are sent from SC to FEF with presaccadic activity being prominent. We hypothesize that a major signal conveyed by the pathway is corollary discharge information about the vector of impending saccades.}, Author = {Sommer, Marc A and Wurtz, Robert H}, Date-Added = {2013-01-29 14:50:40 +0000}, Date-Modified = {2013-01-29 14:53:03 +0000}, Doi = {10.1152/jn.00738.2003}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {visual system; Superior Colliculus; frontal eye field; Frontal Lobe; connectivity; monkey; Macaca mulatta; pulvinar; neurophysiology}, Mesh = {Animals; Blinking; Brain Stem; Electric Stimulation; Electrodes; Electrophysiology; Feedback; Fixation, Ocular; Frontal Lobe; Macaca mulatta; Mediodorsal Thalamic Nucleus; Neurons; Photic Stimulation; Psychomotor Performance; Saccades; Superior Colliculi; Visual Fields; Visual Pathways}, Month = {Mar}, Number = {3}, Pages = {1381-402}, pmid = {14573558}, Pst = {ppublish}, Title = {What the brain stem tells the frontal cortex. I. Oculomotor signals sent from superior colliculus to frontal eye field via mediodorsal thalamus}, Volume = {91}, Year = {2004}, url = {papers/Sommer_JNeurophysiol2004.pdf}} @article{Namiki:2013, Abstract = {Correlated spiking activity prevails in immature cortical networks and is believed to contribute to neuronal circuit maturation; however, its spatiotemporal organization is not fully understood. Using wide-field calcium imaging from acute whole-brain slices of rat pups on postnatal days 1-6, we found that correlated spikes were initiated in the anterior part of the lateral entorhinal cortex and propagated anteriorly to the frontal cortex and posteriorly to the medial entorhinal cortex, forming traveling waves that engaged almost the entire cortex. The waves were blocked by ionotropic glutamatergic receptor antagonists but not by GABAergic receptor antagonists. During wave events, glutamatergic and GABAergic synaptic inputs were balanced and induced UP state-like depolarization. Magnified monitoring with cellular resolution revealed that the layer III neurons were first activated when the waves were initiated. Consistent with this finding, layer III contained a larger number of neurons that were autonomously active, even under a blockade of synaptic transmission. During wave propagation, the layer III neurons constituted a leading front of the wave. The waves did not enter the parasubiculum; however, in some cases, they were reflected at the parasubicular border and propagated back in the opposite direction. During this reflection process, the layer III neurons in the medial entorhinal cortex maintained persistent activity. Thus, our data emphasize the role of layer III in early network behaviors and provide insight into the circuit mechanisms through which cerebral cortical networks maturate.}, Author = {Namiki, Shigehiro and Norimoto, Hiroaki and Kobayashi, Chiaki and Nakatani, Kei and Matsuki, Norio and Ikegaya, Yuji}, Date-Added = {2013-01-29 14:49:39 +0000}, Date-Modified = {2013-08-27 03:10:14 +0000}, Doi = {10.1523/JNEUROSCI.2522-12.2013}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread; in vitro; multiphoton; calcium imaging; development; oscillations; synchrony; spontaneous activity; wholeBrain; currOpinRvw}, Month = {Jan}, Number = {3}, Pages = {987-1001}, pmid = {23325237}, Pst = {ppublish}, Title = {Layer III Neurons Control Synchronized Waves in the Immature Cerebral Cortex}, Volume = {33}, Year = {2013}, url = {papers/Namiki_JNeurosci2013.pdf}} @article{De-la-Rossa:2013, Abstract = {The molecular mechanisms that control how progenitors generate distinct subtypes of neurons, and how undifferentiated neurons acquire their specific identity during corticogenesis, are increasingly understood. However, whether postmitotic neurons can change their identity at late stages of differentiation remains unknown. To study this question, we developed an electrochemical in vivo gene delivery method to rapidly manipulate gene expression specifically in postmitotic neurons. Using this approach, we found that the molecular identity, morphology, physiology and functional input-output connectivity of layer 4 mouse spiny neurons could be specifically reprogrammed during the first postnatal week by ectopic expression of the layer 5B output neuron-specific transcription factor Fezf2. These findings reveal a high degree of plasticity in the identity of postmitotic neocortical neurons and provide a proof of principle for postnatal re-engineering of specific neural microcircuits in vivo.}, Author = {De la Rossa, Andres and Bellone, Camilla and Golding, Bruno and Vitali, Ilaria and Moss, Jonathan and Toni, Nicolas and L{\"u}scher, Christian and Jabaudon, Denis}, Date-Added = {2013-01-29 14:48:45 +0000}, Date-Modified = {2013-01-29 14:49:26 +0000}, Doi = {10.1038/nn.3299}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {toread; development; Neocortex; axon guidance}, Month = {Jan}, Number = {2}, Pages = {193-200}, pmid = {23292682}, Pst = {ppublish}, Title = {In vivo reprogramming of circuit connectivity in postmitotic neocortical neurons}, Volume = {16}, Year = {2013}, url = {papers/DelaRossa_NatNeurosci2013.pdf}} @article{Krey:2013, Abstract = {L-type voltage gated calcium channels have an important role in neuronal development by promoting dendritic growth and arborization. A point mutation in the gene encoding Ca(V)1.2 causes Timothy syndrome, a neurodevelopmental disorder associated with autism spectrum disorders (ASDs). We report that channels with the Timothy syndrome alteration cause activity-dependent dendrite retraction in rat and mouse neurons and in induced pluripotent stem cell (iPSC)-derived neurons from individuals with Timothy syndrome. Dendrite retraction was independent of calcium permeation through the mutant channel, was associated with ectopic activation of RhoA and was inhibited by overexpression of the channel-associated GTPase Gem. These results suggest that Ca(V)1.2 can activate RhoA signaling independently of Ca(2+) and provide insights into the cellular basis of Timothy syndrome and other ASDs.}, Author = {Krey, Jocelyn F and Pa{\c s}ca, Sergiu P and Shcheglovitov, Aleksandr and Yazawa, Masayuki and Schwemberger, Rachel and Rasmusson, Randall and Dolmetsch, Ricardo E}, Date-Added = {2013-01-29 14:47:48 +0000}, Date-Modified = {2013-01-29 14:48:35 +0000}, Doi = {10.1038/nn.3307}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {toread; grants; Calcium Channels; neurological disorder; autism; Autistic Disorder; development}, Month = {Jan}, Number = {2}, Pages = {201-9}, pmid = {23313911}, Pst = {ppublish}, Title = {Timothy syndrome is associated with activity-dependent dendritic retraction in rodent and human neurons}, Volume = {16}, Year = {2013}, url = {papers/Krey_NatNeurosci2013.pdf}} @article{Glickfeld:2013, Abstract = {Neurons in primary sensory cortex have diverse response properties, whereas higher cortical areas are specialized. Specific connectivity may be important for areal specialization, particularly in the mouse, where neighboring neurons are functionally diverse. To examine whether higher visual areas receive functionally specific input from primary visual cortex (V1), we used two-photon calcium imaging to measure responses of axons from V1 arborizing in three areas with distinct spatial and temporal frequency preferences. We found that visual preferences of presynaptic boutons in each area were distinct and matched the average preferences of recipient neurons. This specificity could not be explained by organization within V1 and instead was due to both a greater density and greater response amplitude of functionally matched boutons. Projections from a single layer (layer 5) and from secondary visual cortex were also matched to their target areas. Thus, transmission of specific information to downstream targets may be a general feature of cortico-cortical communication.}, Author = {Glickfeld, Lindsey L and Andermann, Mark L and Bonin, Vincent and Reid, R Clay}, Date-Added = {2013-01-29 14:47:03 +0000}, Date-Modified = {2013-01-29 14:47:41 +0000}, Doi = {10.1038/nn.3300}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {toread; visual cortex; extrastriate; connectivity; adult; mouse; optical imaging; calcium imaging; multiphoton}, Month = {Jan}, Number = {2}, Pages = {219-26}, pmid = {23292681}, Pst = {ppublish}, Title = {Cortico-cortical projections in mouse visual cortex are functionally target specific}, Volume = {16}, Year = {2013}, url = {papers/Glickfeld_NatNeurosci2013.pdf}} @article{Beltramo:2013, Abstract = {In the absence of external stimuli, the mammalian neocortex shows intrinsic network oscillations. These dynamics are characterized by translaminar assemblies of neurons whose activity synchronizes rhythmically in space and time. How different cortical layers influence the formation of these spontaneous cellular assemblies is poorly understood. We found that excitatory neurons in supragranular and infragranular layers have distinct roles in the regulation of intrinsic low-frequency oscillations in mice in vivo. Optogenetic activation of infragranular neurons generated network activity that resembled spontaneous events, whereas photoinhibition of these same neurons substantially attenuated slow ongoing dynamics. In contrast, light activation and inhibition of supragranular cells had modest effects on spontaneous slow activity. This study represents, to the best of our knowledge, the first causal demonstration that excitatory circuits located in distinct cortical layers differentially control spontaneous low-frequency dynamics.}, Author = {Beltramo, Riccardo and D'Urso, Giulia and Dal Maschio, Marco and Farisello, Pasqualina and Bovetti, Serena and Clovis, Yoanne and Lassi, Glenda and Tucci, Valter and De Pietri Tonelli, Davide and Fellin, Tommaso}, Date-Added = {2013-01-29 14:46:16 +0000}, Date-Modified = {2013-01-29 14:46:55 +0000}, Doi = {10.1038/nn.3306}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {toread; slow oscillations; Delta Rhythm; Neocortex; optogenetics; neurophysiology}, Month = {Jan}, Number = {2}, Pages = {227-34}, pmid = {23313909}, Pst = {ppublish}, Title = {Layer-specific excitatory circuits differentially control recurrent network dynamics in the neocortex}, Volume = {16}, Year = {2013}, url = {papers/Beltramo_NatNeurosci2013.pdf}} @article{Brecht:2011, Abstract = {In this issue, two studies, by Ehrlich et al. and Hill et al., address the role of the frontal motor cortices in behavior of the rat and suggest a potential role for this structure in high-level control of diverse behaviors. Hill et al. show that motor cortical neurons predict whisker movements even without sensory feedback and that their activity reflects efferent control. Surprisingly, Ehrlich et al. report the participation of this same cortical region in the preparation and execution of orienting behaviors.}, Author = {Brecht, Michael}, Date-Added = {2013-01-29 14:45:07 +0000}, Date-Modified = {2013-01-29 14:46:07 +0000}, Doi = {10.1016/j.neuron.2011.10.002}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {toread; function; connectivity; rat; Frontal Lobe; frontal eye field; cerebral cortex}, Mesh = {Animals; Female; Frontal Lobe; Male; Memory; Motor Cortex; Neurons; Orientation; Vibrissae; Visual Pathways}, Month = {Oct}, Number = {2}, Pages = {193-6}, pmid = {22017982}, Pst = {ppublish}, Title = {Movement, confusion, and orienting in frontal cortices}, Volume = {72}, Year = {2011}, url = {papers/Brecht_Neuron2011.pdf}} @article{Arvanitis:2008, Abstract = {Bidirectional signaling has emerged as an important signature by which Ephs and ephrins control biological functions. Eph/ephrin signaling participates in a wide spectrum of developmental processes, and cross-regulation with other communication pathways lies at the heart of the complexity underlying their function in vivo. Here, we review in vitro and in vivo data describing molecular, functional, and genetic interactions between Eph/ephrin and other cell surface signaling pathways. The complexity of Eph/ephrin function is discussed in terms of the pathways that regulate Eph/ephrin signaling and also the pathways that are regulated by Eph/ephrin signaling.}, Author = {Arvanitis, Dina and Davy, Alice}, Date-Added = {2013-01-29 14:42:52 +0000}, Date-Modified = {2013-01-29 14:44:34 +0000}, Doi = {10.1101/gad.1630408}, Journal = {Genes Dev}, Journal-Full = {Genes \& development}, Keywords = {review literature; calcium; Ephrins; development; synaptogenesis; grants}, Mesh = {Animals; Cell Adhesion; Cell Movement; Ephrins; Humans; Receptor Cross-Talk; Receptors, Eph Family; Signal Transduction}, Month = {Feb}, Number = {4}, Pages = {416-29}, Pmc = {PMC2731651}, pmid = {18281458}, Pst = {ppublish}, Title = {Eph/ephrin signaling: networks}, Volume = {22}, Year = {2008}, url = {papers/Arvanitis_GenesDev2008.pdf}} @article{Prigge:2012, Abstract = {Channelrhodopsin-2 is a light-gated ion channel and a major tool of optogenetics. It is used to control neuronal activity via blue light. Here we describe the construction of color-tuned high efficiency channelrhodopsins (ChRs), based on chimeras of Chlamydomonas channelrhodopsin-1 and Volvox channelrhodopsin-1. These variants show superb expression and plasma membrane integration, resulting in 3-fold larger photocurrents in HEK cells compared with channelrhodopsin-2. Further molecular engineering gave rise to chimeric variants with absorption maxima ranging from 526 to 545 nm, dovetailing well with maxima of channelrhodopsin-2 derivatives ranging from 461 to 492 nm. Additional kinetic fine-tuning led to derivatives in which the lifetimes of the open state range from 19 ms to 5 s. Finally, combining green- with blue-absorbing variants allowed independent activation of two distinct neural cell populations at 560 and 405 nm. This novel panel of channelrhodopsin variants may serve as an important toolkit element for dual-color cell stimulation in neural circuits.}, Author = {Prigge, Matthias and Schneider, Franziska and Tsunoda, Satoshi P and Shilyansky, Carrie and Wietek, Jonas and Deisseroth, Karl and Hegemann, Peter}, Date-Added = {2013-01-21 19:28:41 +0000}, Date-Modified = {2013-01-21 19:29:04 +0000}, Doi = {10.1074/jbc.M112.391185}, Journal = {J Biol Chem}, Journal-Full = {The Journal of biological chemistry}, Keywords = {technique; methods; optogenetics}, Mesh = {Animals; Calcium; Chlamydomonas; Color; Electrophysiology; Genetic Engineering; HEK293 Cells; Hippocampus; Humans; Ions; Kinetics; Light; Models, Neurological; Oocytes; Optogenetics; Recombinant Fusion Proteins; Rhodopsin; Volvox; Xenopus}, Month = {Sep}, Number = {38}, Pages = {31804-12}, Pmc = {PMC3442514}, pmid = {22843694}, Pst = {ppublish}, Title = {Color-tuned channelrhodopsins for multiwavelength optogenetics}, Volume = {287}, Year = {2012}, url = {papers/Prigge_JBiolChem2012.pdf}} @article{Schoppik:2006, Abstract = {Saccades modulate the relationship between visual motion and smooth eye movement. Before a saccade, pursuit eye movements reflect a vector average of motion across the visual field. After a saccade, pursuit primarily reflects the motion of the target closest to the endpoint of the saccade. We tested the hypothesis that the saccade produces a spatial weighting of motion around the endpoint of the saccade. Using a moving pursuit stimulus that stepped to a new spatial location just before a targeting saccade, we controlled the distance between the endpoint of the saccade and the position of the moving target. We demonstrate that the smooth eye velocity following the targeting saccade weights the presaccadic visual motion inputs by the distance from their location in space to the endpoint of the saccade, defining the extent of a spatiotemporal filter for driving the eyes. The center of the filter is located at the endpoint of the saccade in space, not at the position of the fovea. The filter is stable in the face of a distracter target, is present for saccades to stationary and moving targets, and affects both the speed and direction of the postsaccadic eye movement. The spatial filter can explain the target-selecting gain change in postsaccadic pursuit, and has intriguing parallels to the process by which perceptual decisions about a restricted region of space are enhanced by attention. The effect of the spatial saccade plan on the pursuit response to a given retinal motion describes the dynamics of a coordinate transformation.}, Author = {Schoppik, David and Lisberger, Stephen G}, Date-Added = {2013-01-11 14:12:44 +0000}, Date-Modified = {2013-01-11 14:13:01 +0000}, Doi = {10.1523/JNEUROSCI.1719-06.2006}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread}, Mesh = {Animals; Macaca mulatta; Male; Models, Biological; Motion Perception; Photic Stimulation; Pursuit, Smooth; Saccades; Space Perception}, Month = {Jul}, Number = {29}, Pages = {7607-18}, Pmc = {PMC2548311}, pmid = {16855088}, Pst = {ppublish}, Title = {Saccades exert spatial control of motion processing for smooth pursuit eye movements}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1719-06.2006}} @article{Schoppik:2008, Abstract = {Neural activity in the frontal eye fields controls smooth pursuit eye movements, but the relationship between single neuron responses, cortical population responses, and eye movements is not well understood. We describe an approach to dynamically link trial-to-trial fluctuations in neural responses to parallel variations in pursuit and demonstrate that individual neurons predict eye velocity fluctuations at particular moments during the course of behavior, while the population of neurons collectively tiles the entire duration of the movement. The analysis also reveals the strength of correlations in the eye movement predictions derived from pairs of simultaneously recorded neurons and suggests a simple model of cortical processing. These findings constrain the primate cortical code for movement, suggesting that either a few neurons are sufficient to drive pursuit at any given time or that many neurons operate collectively at each moment with remarkably little variation added to motor command signals downstream from the cortex.}, Author = {Schoppik, David and Nagel, Katherine I and Lisberger, Stephen G}, Date-Added = {2013-01-11 14:12:42 +0000}, Date-Modified = {2013-01-11 14:13:01 +0000}, Doi = {10.1016/j.neuron.2008.02.015}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {toread}, Mesh = {Action Potentials; Animals; Behavior, Animal; Brain Mapping; Cerebral Cortex; Macaca mulatta; Male; Models, Neurological; Neurons; Nonlinear Dynamics; Numerical Analysis, Computer-Assisted; Photic Stimulation; Pursuit, Smooth; Reaction Time; Stereotyped Behavior}, Month = {Apr}, Number = {2}, Pages = {248-60}, Pmc = {PMC2426736}, pmid = {18439409}, Pst = {ppublish}, Title = {Cortical mechanisms of smooth eye movements revealed by dynamic covariations of neural and behavioral responses}, Volume = {58}, Year = {2008}, url = {papers/Schoppik_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.02.015}} @article{McConnell:1988, Abstract = {In the mammalian cerebral cortex, neurons in a given layer are generated at about the same time in development. These cells also tend to share similar sets of morphological and physiological properties and have projection patterns characteristic of that layer. This correspondence between the birthday and eventual fate of a cortical neuron suggests the possibility that the commitment of a cell to a particular laminar position and set of connections may occur very early on in cortical development. The experiments described here constitute an attempt to manipulate the fates of newly generated cortical neurons upon transplantation. The first set of experiments addressed the normal development of neurons in the primary visual cortex (area 17) of the ferret. Injections of 3H-thymidine into newborn ferrets showed that neurons generated after birth are destined to sit in layer 2/3 of the cortex, whereas neurons born on embryonic day (E) 32 populate primarily layers 5 and 6. Many layer 2/3 neurons in adult ferrets could be retrogradely labeled with HRP from visual cortical areas 18 and 19, while about half of the neurons in layer 6 were found to project to the lateral geniculate nucleus (LGN). In the second set of experiments, presumptive layer 2/3 cells were labeled in vivo by injecting ferrets with 3H-thymidine on P1 and P2. Before the cells had a chance to migrate, they were removed from the donor brain, incubated in a fluorescent dye (DAPI or fast blue), and dissociated into a single-cell suspension. The labeled cells were then transplanted into the proliferative zone of a littermate host ferret ("isochronic" transplants). Over the next few weeks, many of these dye-labeled cells underwent changes in their position and morphology that were consistent with a radially directed migration and subsequent differentiation into cortical neurons. The final positions of isochronically transplanted neurons in the host brain were mapped out by using the 3H-thymidine marker after long survival periods. About 97% of radioactively labeled cells had migrated out into the visual cortex, where they attained a compact laminar distribution: 99% were found in layer 2/3, their normal destination. The labeled cells had normal, mostly pyramidal neuronal morphologies and appeared to be well integrated with host neurons when viewed in Nissl-stained sections. Ten isochronically transplanted neurons were successfully labeled after HRP injection into 2 normal target regions, areas 18 and 19.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {McConnell, S K}, Date-Added = {2012-12-19 17:50:54 +0000}, Date-Modified = {2012-12-19 17:50:54 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Animals; Cell Movement; Ferrets; Neural Pathways; Neurons; Thymidine; Transplantation; Visual Cortex}, Month = {Mar}, Number = {3}, Pages = {945-74}, pmid = {3346731}, Pst = {ppublish}, Title = {Fates of visual cortical neurons in the ferret after isochronic and heterochronic transplantation}, Volume = {8}, Year = {1988}} @article{McConnell:1985, Abstract = {Cells from the cerebral proliferative zones of newborn ferrets were labeled with tritiated thymidine and a fluorescent dye and were transplanted as a single-cell suspension into the occipital region of newborn ferrets. The transplanted cells became thoroughly integrated into the host environment: many cells migrated through the intermediate zone and into the cortical plate, where they developed as pyramidal neurons. Other transplanted cells came to resemble glial cells. After 1 to 2 months most transplanted neurons had taken up residence in layer 2 + 3, the normal destination of neurons generated on postnatal days 1 and 2. Thus the sequence of morphological differentiation and the eventual laminar position of the isochronically transplanted neurons closely paralleled that of their normal host counterparts.}, Author = {McConnell, S K}, Date-Added = {2012-12-19 17:50:31 +0000}, Date-Modified = {2012-12-19 17:50:31 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Mesh = {Amidines; Animals; Animals, Newborn; Autoradiography; Cell Differentiation; Cell Movement; Cerebral Cortex; Ferrets; Fluorescent Dyes; Indoles; Neurons}, Month = {Sep}, Number = {4719}, Pages = {1268-71}, pmid = {4035355}, Pst = {ppublish}, Title = {Migration and differentiation of cerebral cortical neurons after transplantation into the brains of ferrets}, Volume = {229}, Year = {1985}} @article{OLeary:1989a, Abstract = {In adult rats, cortical neurons that extend an exon through the pyramidal tract (a major subcortical efferent projection of the neocortex) are limited to layer V of about the rostral two-thirds of the neocortex. In neonates, however, pyramidal tract neurons are distributed throughout the neocortex, but all of those found in certain areas, such as the posterior occipital region (including primary visual cortex) selectively lose their pyramidal tract axon (Stanfield et al., 1982) yet maintain axon collaterals to other subcortical targets (O'Leary and Stanfield, 1985). To determine if the regional location of a developing pyramidal tract neuron critically influences the maintenance or elimination of the axon collaterals it initially extends, pieces of cortex from embryonic day 17 (E17) rat fetuses (exposed to 3H-thymidine on E15) were transplanted heterotopically into the cortex of newborn (PO) rats; rostral cortex was placed into the posterior occipital region (R----O), or posterior occipital cortex into a rostral cortical locale (O----R). The retrograde tracers Fast blue (FB) and Diamidino yellow (DY) were used to assay for the presence of specific populations of cortical projection neurons within the autoradiographically identified transplants. In terms of the extension and maintenance of pyramidal tract axons, the transplanted neurons behave like the host neurons of the recipient cortical region rather than like those of their site of origin. At P40, following FB injections into the pyramidal decussation on P34, pyramidal tract neurons are labeled within the O----R transplants, but none can be labeled within R----O transplants, although in the same R----O cases transplanted neurons are labeled by an injection of DY in the superior colliculus. However, at P13 pyramidal tract neurons can be identified within the R----O transplants, as well as in the host occipital cortex, following injections made on P9, a period when the distribution of pyramidal tract neurons in normal rats is widespread (Stanfield and O'Leary, 1985b). In a second series of host rats, on P34 FB was injected in the pyramidal decussation of the O----R cases, or in the superior colliculus of the R----O cases, and in both groups DY was injected into the region of contralateral cortex homotopic for the new location of the transplant. On P40, in both the O----R and R----O transplants, many neurons singly labeled with FB or DY are found, but no double dye-labeled cells are seen.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {O'Leary, D D and Stanfield, B B}, Date-Added = {2012-12-19 17:45:09 +0000}, Date-Modified = {2012-12-19 17:48:55 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; map; topographic map; activity manipulation; Activity-development; gene; cell fate; connectivity}, Mesh = {Animals; Animals, Newborn; Axons; Cerebral Cortex; Female; Occipital Lobe; Pyramidal Tracts; Rats; Rats, Inbred Strains; Synaptic Transmission; Transplantation, Heterologous}, Month = {Jul}, Number = {7}, Pages = {2230-46}, pmid = {2545833}, Pst = {ppublish}, Title = {Selective elimination of axons extended by developing cortical neurons is dependent on regional locale: experiments utilizing fetal cortical transplants}, Volume = {9}, Year = {1989}} @article{OLeary:1989, Abstract = {The adult mammalian neocortex consists of numerous 'areas' distinguished from one another largely on the basis of distinctions in cytoarchitecture and connections. The developing neocortex, though, lacks many of these area-specific distinctions, and is more uniform across its extent. This less differentiated structure, here termed the 'protocortex' undergoes considerable modification after neurogenesis which results in the emergence of well-defined neocortical areas. To what extent, then, are neocortical areas predetermined? This issue is considered in the context of recent findings on the generation of the neocortex and its subsequent parcellation into distinct areas.}, Author = {O'Leary, D D}, Date-Added = {2012-12-19 17:45:04 +0000}, Date-Modified = {2012-12-19 17:49:01 +0000}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {development; map; topographic map; activity manipulation; Activity-development; gene; cell fate; connectivity}, Mesh = {Aging; Animals; Cerebral Cortex; Embryonic and Fetal Development}, Month = {Oct}, Number = {10}, Pages = {400-6}, pmid = {2479138}, Pst = {ppublish}, Title = {Do cortical areas emerge from a protocortex?}, Volume = {12}, Year = {1989}} @article{Steele:1999, Abstract = {We investigated the role of NMDA receptors in memory encoding and retrieval. A delayed matching-to-place (DMP) paradigm in the watermaze was used to examine 1-trial spatial memory in rats. Over periods of up to 21 days, 4 daily trials were given to an escape platform hidden in a new location each day, with the memory interval (ITI) varying from 15 sec to 2 hours between trials 1 and 2, but always at 15 sec for the remaining ITIs. Using chronic i.c.v. infusions of D-AP5, acute intrahippocampal infusions, ibotenate hippocampus + dentate lesions and relevant aCSF or sham surgery control groups, we established: (1) the DMP task is hippocampal-dependent; (2) D-AP5 causes a delay-dependent impairment of memory in which the Groups x Delay interaction was significant on two separate measures of performance; (3) this memory impairment also occurs with acute intrahippocampal infusions; (4) the impairment occurs irrespective of whether the animals stay in or are removed from the training context during the memory delay interval; and (5) D-AP5 affects neither the retrieval of information about the spatial layout of the environment, nor memory of where the escape platform had been located on the last day before the start of chronic D-AP5 infusion. LTP in vivo in the dentate gyrus was blocked in the chronically-infused D-AP5 rats and HPLC measurements at sacrifice revealed appropriate intrahippocampal levels. Acute intrahippocampal infusion of radiolabelled D-AP5 revealed relatively restricted diffusion and was used to estimate whole-tissue hippocampal drug concentrations. These results indicate that (1) short-term memory for spatial information is independent of NMDA receptors; (2) the rapid consolidation of spatial information into long-term memory requires activation of hippocampal NMDA receptors; (3) NMDA receptors are not involved in memory retrieval; and (4) the delay-related effects of NMDA receptor antagonists on performance of this task cannot be explained in terms of sensorimotor disturbances. The findings relate to the idea that hippocampal synaptic plasticity is involved in event-memory (Morris and Frey, Phil Trans R Soc Lond B 1997;352:1489-1503) and to a computational model of one-trial DMP performance of Foster et al. (unpublished data).}, Author = {Steele, R J and Morris, R G}, Date-Added = {2012-12-12 18:31:17 +0000}, Date-Modified = {2012-12-12 18:31:17 +0000}, Doi = {10.1002/(SICI)1098-1063(1999)9:2<118::AID-HIPO4>3.0.CO;2-8}, Journal = {Hippocampus}, Journal-Full = {Hippocampus}, Mesh = {2-Amino-5-phosphonovalerate; Animals; Autoradiography; Behavior, Animal; Chromatography, High Pressure Liquid; Excitatory Amino Acid Antagonists; Hippocampus; Long-Term Potentiation; Male; Maze Learning; Memory, Short-Term; Microinjections; Psychomotor Performance; Rats; Rats, Inbred Strains; Reaction Time; Receptors, N-Methyl-D-Aspartate; Space Perception; Tritium}, Number = {2}, Pages = {118-36}, pmid = {10226773}, Pst = {ppublish}, Title = {Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist D-AP5}, Volume = {9}, Year = {1999}, url = {papers/Steele_Hippocampus1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1098-1063(1999)9:2%3C118::AID-HIPO4%3E3.0.CO;2-8}} @article{Ferrer:1988, Abstract = {Retrogradely transported tracers were injected into area 18 of the visual cortex of the adult cat to study the organization of corticocortical projections from area 17 to area 18. All injections, whether very small or relatively large, and irrespective of their exact location in area 18, produced a discontinuous, clustered distribution of labelled cells, mainly in layers II, III and upper IV, in a topographically related region of area 17. The mean centre-centre distance between neighbouring patches was about 750 microns. We conclude that the overall population of cells projecting to area 18 is genuinely distributed in a patchy fashion and that they provide an efficient spatial sample of information from area 17. Comparison of the dimensions of each injection site and of the retrogradely labelled territory suggested that each region in area 18 receives a convergent input from a zone in area 17 whose visual field representation is about 0.8 M-1 deg larger in all directions (where M is the magnification factor in millimetres per degree at the termination site in area 18). Pairs of injection were made in area 18 by placing small volumes of two fluorescent tracers, fast blue and diamidino yellow, side-by-side in either a rostrocaudal or a mediolateral plane, with different distances between them. When the boundaries of the dense central cores of two injection sites were separated, at their closest points, by about 1.6 mm, the two corresponding distributions of labelled cells in area 17 were just non-overlapping, suggesting that each group of cells in area 17 sends a divergent projection in innervate a zone about 0.8 mm larger in all directions in area 18. More closely spaced injections led to overlap of the distributions of labelling by the two dyes, with shared clusters containing a mixture of labelled cells. The proportion of double-labelled cells in these shared clusters never exceeded 4.4% (but was 70% after sequential injection of the two dyes at a single point). We conclude that, although each cluster of cells sends a divergent projection to area 18, the majority of individual axons terminate more discretely, perhaps providing specific inter-connections between functionally corresponding 'columns' in the two areas.}, Author = {Ferrer, J M and Price, D J and Blakemore, C}, Date-Added = {2012-12-11 15:58:56 +0000}, Date-Modified = {2012-12-11 15:58:56 +0000}, Journal = {Proc R Soc Lond B Biol Sci}, Journal-Full = {Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)}, Mesh = {Animals; Cats; Microscopy, Fluorescence; Neurons; Visual Cortex}, Month = {Feb}, Number = {1270}, Pages = {77-98}, pmid = {2895934}, Pst = {ppublish}, Title = {The organization of corticocortical projections from area 17 to area 18 of the cat's visual cortex}, Volume = {233}, Year = {1988}, url = {papers/Ferrer_ProcRSocLondBBiolSci1988.pdf}} @article{King:1988, Abstract = {Environmental factors play an important role in certain aspects of the development of sensory systems. But the way in which the maturation of different sensory modalities is coordinated is poorly understood. We have investigated this question neurophysiologically in the mammalian superior colliculus (SC), which contains topographically aligned maps of visual and auditory space. We report here that an essentially normal auditory map, in approximate register with the visual map, is found in the SC of adult ferrets reared with abnormal binaural localization cues. Also, if, early in life, one eye is deviated laterally, there is a compensatory shift in the auditory map, but early eye rotation totally disorders the auditory representation. These results imply that development of the auditory map is affected by visual activity or by information about eye position and that there is definite, but limited, capacity for the auditory map to reorganize so that it remains aligned with the visual map.}, Author = {King, A J and Hutchings, M E and Moore, D R and Blakemore, C}, Date-Added = {2012-12-11 15:58:31 +0000}, Date-Modified = {2012-12-11 15:58:31 +0000}, Doi = {10.1038/332073a0}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Acoustic Stimulation; Animals; Carnivora; Eye; Ferrets; Hearing; Neurons; Ocular Physiological Phenomena; Superior Colliculi; Vision, Ocular; Visual Fields}, Month = {Mar}, Number = {6159}, Pages = {73-6}, pmid = {3347247}, Pst = {ppublish}, Title = {Developmental plasticity in the visual and auditory representations in the mammalian superior colliculus}, Volume = {332}, Year = {1988}, url = {papers/King_Nature1988.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/332073a0}} @article{Stein:2008, Abstract = {For thousands of years science philosophers have been impressed by how effectively the senses work together to enhance the salience of biologically meaningful events. However, they really had no idea how this was accomplished. Recent insights into the underlying physiological mechanisms reveal that, in at least one circuit, this ability depends on an intimate dialogue among neurons at multiple levels of the neuraxis; this dialogue cannot take place until long after birth and might require a specific kind of experience. Understanding the acquisition and usage of multisensory integration in the midbrain and cerebral cortex of mammals has been aided by a multiplicity of approaches. Here we examine some of the fundamental advances that have been made and some of the challenging questions that remain.}, Author = {Stein, Barry E and Stanford, Terrence R}, Date-Added = {2012-12-11 15:15:04 +0000}, Date-Modified = {2012-12-11 15:15:04 +0000}, Doi = {10.1038/nrn2331}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Mesh = {Afferent Pathways; Animals; Brain Mapping; Cerebral Cortex; Humans; Mental Processes; Neurons; Sensation}, Month = {Apr}, Number = {4}, Pages = {255-66}, pmid = {18354398}, Pst = {ppublish}, Title = {Multisensory integration: current issues from the perspective of the single neuron}, Volume = {9}, Year = {2008}, url = {papers/Stein_NatRevNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2331}} @article{Mu:2012, Abstract = {Visual cues often modulate auditory signal processing, leading to improved sound detection. However, the synaptic and circuit mechanism underlying this cross-modal modulation remains poorly understood. Using larval zebrafish, we first established a cross-modal behavioral paradigm in which a preceding flash enhances sound-evoked escape behavior, which is known to be executed through auditory afferents (VIII(th) nerves) and command-like neurons (Mauthner cells). In vivo recording revealed that the visual enhancement of auditory escape is achieved by increasing sound-evoked Mauthner cell responses. This increase in Mauthner cell responses is accounted for by the increase in the signal-to-noise ratio of sound-evoked VIII(th) nerve spiking and efficacy of VIII(th) nerve-Mauthner cell synapses. Furthermore, the visual enhancement of Mauthner cell response and escape behavior requires light-responsive dopaminergic neurons in the caudal hypothalamus and D1 dopamine receptor activation. Our findings illustrate a cooperative neural mechanism for visual modulation of audiomotor processing that involves dopaminergic neuromodulation.}, Author = {Mu, Yu and Li, Xiao-quan and Zhang, Bo and Du, Jiu-lin}, Date-Added = {2012-12-11 14:45:16 +0000}, Date-Modified = {2012-12-11 14:47:57 +0000}, Doi = {10.1016/j.neuron.2012.05.035}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {multimodal; Activity-development; activity manipulation; sensory map; Motor Activity; neurophysiology; Zebrafish; development; Auditory Pathways; visual system; plasticity; Dopamine; potentiation; Adaptation; habituation;}, Mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione; Acoustic Stimulation; Action Potentials; Animals; Apomorphine; Behavior, Animal; Benzazepines; Biotin; Cell Communication; Dopamine Agonists; Dopamine Antagonists; Dopaminergic Neurons; Escape Reaction; Excitatory Amino Acid Agonists; Excitatory Postsynaptic Potentials; Flufenamic Acid; Functional Laterality; Glycyrrhetinic Acid; Hypothalamus; Larva; Light; Locomotion; Microscopy, Confocal; Morpholinos; Patch-Clamp Techniques; Photic Stimulation; Psychoacoustics; Receptors, Dopamine D1; Signal-To-Noise Ratio; Time Factors; Valine; Visual Pathways; Zebrafish}, Month = {Aug}, Number = {4}, Pages = {688-99}, pmid = {22920259}, Pst = {ppublish}, Title = {Visual input modulates audiomotor function via hypothalamic dopaminergic neurons through a cooperative mechanism}, Volume = {75}, Year = {2012}, url = {papers/Mu_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.05.035}} @article{Salin:1989, Abstract = {We have examined the topography of the afferent connections to area 17 in the cat by means of double retrograde label tracing techniques. Injections of two fluorescent retrograde tracers, diamidino yellow and fast blue, were made with variable separations in area 17 and the spatial distributions of the resulting populations of labeled cells examined in afferent cortical areas and subcortical structures. When injections were separated rostrocaudally, the topographic organizations of the projections were characterized quantitatively with two graphic methods: the labeling density curve and the connectivity graph. The labeling density curve measures labeled neuron density in successive rostrocaudal sections, whereas the connectivity graph provides a two-dimensional model of the topography of a given connectivity. The connectivity graph makes it possible to define two parameters that characterize the topography of the connection: the convergence and the divergence. The convergence is defined as the extent of an afferent structure that contains neurons converging on a line normal to the cortical surface in area 17. The divergence is the extent of area 17 that is innervated by neurons contained in an infinitely small region of the afferent structure. The results show that a number of subcortical structures project to area 17 in a nontopographic manner, i.e., that in each of these structures neurons contained in an infinitely small region send projections to the whole of area 17 and that a line normal to the surface of area 17 is innervated by neurons distributed throughout the afferent structure in question. Nontopographic projections are found from the intralaminar nuclei, the ventral mesencephalic tegmental region, the diagonal band of Broca, and the locus coeruleus. All remaining subcortical structures and cortical areas send topographically organized projections to area 17. The extent of the convergence and divergence, however, varies between structures. Only the projection from the A laminae of the LGN was found to approximate a point-to-point projection with a convergence of 0.4 mm and 2 mm in divergence. Much larger convergence and divergence values are found in the projections from the claustrum and the cortical areas. For example, the divergence reaches 20 mm for the projections from area 20 or from the anterior part of the lateral suprasylvian sulcus. Knowing the convergence and divergence values and the retinotopic organizations of area 17 and a number of its afferents, it becomes possible to test whether connections in the visual system link regions representing the same zone of the visual field.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Salin, P A and Bullier, J and Kennedy, H}, Date-Added = {2012-12-11 13:59:40 +0000}, Date-Modified = {2012-12-11 14:01:33 +0000}, Doi = {10.1002/cne.902830405}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {mirror symmetry; Corpus Callosum; cat; Histological Techniques; histology; visual system; visual cortex; Neocortex; topographic map; brain mapping; graph theory; toread}, Mesh = {Afferent Pathways; Animals; Brain Mapping; Cats; Fluorescent Dyes; Visual Cortex; Visual Pathways}, Month = {May}, Number = {4}, Pages = {486-512}, pmid = {2745751}, Pst = {ppublish}, Title = {Convergence and divergence in the afferent projections to cat area 17}, Volume = {283}, Year = {1989}, url = {papers/Salin_JCompNeurol1989.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902830405}} @article{Olavarria:2012, Abstract = {Callosal connections form elaborate patterns that bear close association with striate and extrastriate visual areas. Although it is known that retinal input is required for normal callosal development, there is little information regarding the period during which the retina is critically needed and whether this period correlates with the same developmental stage across species. Here we review the timing of this critical period, identified in rodents and ferrets by the effects that timed enucleations have on mature callosal connections, and compare it to other developmental milestones in these species. Subsequently, we compare these events to diffusion tensor imaging (DTI) measurements of water diffusion anisotropy within developing cerebral cortex. We observed that the relationship between the timing of the critical period and the DTI-characterized developmental trajectory is strikingly similar in rodents and ferrets, which opens the possibility of using cortical DTI trajectories for predicting the critical period in species, such as humans, in which this period likely occurs prenatally. Last, we discuss the potential of utilizing DTI to distinguish normal from abnormal cerebral cortical development, both within the context of aberrant connectivity induced by early retinal deafferentation, and more generally as a potential tool for detecting abnormalities associated with neurodevelopmental disorders.}, Author = {Olavarria, Jaime F and Bock, Andrew S and Leigland, Lindsey A and Kroenke, Christopher D}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:14:04 +0000}, Doi = {10.1155/2012/250196}, Journal = {Neural Plast}, Journal-Full = {Neural plasticity}, Keywords = {visual system, connectivity, visual cortex, neocortex, histology, spontaneous activity, retina, brain mapping, mirror symmetry, corpus callosum}, Pages = {250196}, pmid = {23213572}, Pst = {ppublish}, Title = {Deafferentation-induced plasticity of visual callosal connections: predicting critical periods and analyzing cortical abnormalities using diffusion tensor imaging}, Volume = {2012}, Year = {2012}, url = {papers/Olavarria_NeuralPlast2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1155/2012/250196}} @article{Laing:2012, Abstract = {Previous studies have shown that retinal input plays an important role in the development of interhemispheric callosal connections, but little is known about the role retinal input plays on the development of ipsilateral striate-extrastriate connections and the interplay that might exist between developing ipsilateral and callosal pathways. We analyzed the effects of bilateral enucleation performed at different ages on both the distribution of extrastriate projections originating from restricted loci in medial, acallosal striate cortex, and the overall pattern of callosal connections revealed following multiple tracer injections. As in normal rats, striate-extrastriate projections in rats enucleated at birth consisted of multiple, well-defined fields that were largely confined to acallosal regions throughout extrastriate cortex. However, these projections were highly irregular and variable, and they tended to occupy correspondingly anomalous and variable acallosal regions. Moreover, area 17, but not area 18a, was smaller in enucleates compared to controls, resulting in an increase in the divergence of striate projections. Anomalies in patterns of striate-extrastriate projections were not observed in rats enucleated at postnatal day (P)6, although the size of area 17 was still reduced in these rats. These results indicate that the critical period during which the eyes influence the development of striate-extrastriate, but not the size of striate cortex, ends by P6. Finally, enucleation did not change the time course and definition of the initial invasion of axons into gray matter, suggesting that highly variable striate projections patterns do not result from anomalous pruning of exuberant distributions of 17-18a fibers in gray matter.}, Author = {Laing, R J and Bock, A S and Lasiene, J and Olavarria, J F}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:20:19 +0000}, Doi = {10.1002/cne.23096}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {visual system, connectivity, visual cortex, neocortex, histology, spontaneous activity, retina, brain mapping, mirror symmetry, corpus callosum, toread}, Month = {Oct}, Number = {14}, Pages = {3256-76}, pmid = {22430936}, Pst = {ppublish}, Title = {Role of retinal input on the development of striate-extrastriate patterns of connections in the rat}, Volume = {520}, Year = {2012}, url = {papers/Laing_JCompNeurol2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.23096}} @article{Bock:2012, Abstract = {Retinal input plays an important role in the specification of topographically organized circuits and neuronal response properties, but the mechanism and timing of this effect is not known in most species. A system that shows dramatic dependence on retinal influences is the interhemispheric connection through the corpus callosum. Using ferrets, we analyzed the extent to which development of the visual callosal pattern depends on retinal influences, and explored the period during which these influences are required for normal pattern formation. We studied the mature callosal patterns in normal ferrets and in ferrets bilaterally enucleated (BE) at postnatal day 7 (P7) or P20. Callosal patterns were revealed in tangential sections from unfolded and flattened brains following multiple injections of horseradish peroxidase in the opposite hemisphere. We also estimated the effect of enucleation on the surface areas of striate and extrastriate visual cortex by using magnetic resonance imaging (MRI) data from intact brains. In BEP7 ferrets we found that the pattern of callosal connections was highly anomalous and the sizes of both striate and extrastriate visual cortex were significantly reduced. In contrast, enucleation at P20 had no significant effect on the callosal pattern, but it still caused a reduction in the size of striate and extrastriate visual cortex. Finally, retinal deafferentation had no significant effect on the number of visual callosal neurons. These results indicate that the critical period during which the eyes influence the development of callosal patterns, but not the size of visual cortex, ends by P20 in the ferret.}, Author = {Bock, A S and Kroenke, C D and Taber, E N and Olavarria, J F}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:20:27 +0000}, Doi = {10.1002/cne.22738}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {currOpinRvw; visual system; connectivity; visual cortex; neocortex; histology; spontaneous activity; retina; brain mapping; mirror symmetry; corpus callosum; toread}, Mesh = {Animals; Animals, Newborn; Corpus Callosum; Eye Enucleation; Ferrets; Retina; Visual Cortex; Visual Pathways}, Month = {Apr}, Number = {5}, Pages = {914-32}, pmid = {21830218}, Pst = {ppublish}, Title = {Retinal input influences the size and corticocortical connectivity of visual cortex during postnatal development in the ferret}, Volume = {520}, Year = {2012}, url = {papers/Bock_JCompNeurol2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.22738}} @article{Bock:2011a, Abstract = {Previous studies have reported that intrahemispheric connections between area 17 (V1, striate cortex) and other cortical visual areas are not point-to-point, but instead have some degree of convergence and divergence. Many pathological conditions can interfere with the normal development of patterns of cortico-cortical connections, but there is little information regarding whether or not early pathological insults can also induce permanent changes in the convergence and divergence of cortical connections. Obtaining this information is important because loss of precision in neural projections can contribute to functional deficits and behavioral impairment. In the present study we investigated whether retinal input is required for the development of normal values of convergence and divergence in the visual callosal pathway. We found that enucleation performed at birth induced significant increases in convergence and divergence compared to control animals. In contrast, values of convergence and divergence in rats enucleated at postnatal day 7 (P7) were similar to those in controls. Previous studies have shown that retinal input during the first postnatal week is required for the specification of the overall distribution and internal topography of visual callosal pathways. Our present results therefore extend these previous finding by showing that retinal input during the first postnatal week also specifies the precision of cortico-cortical projections. These findings raise the possibility that the precision of neural connections may be reduced in other pathological conditions that affect early development of neural connections.}, Author = {Bock, A S and Olavarria, J F}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:14:04 +0000}, Doi = {10.1016/j.neulet.2011.07.005}, Journal = {Neurosci Lett}, Journal-Full = {Neuroscience letters}, Keywords = {visual system, connectivity, visual cortex, neocortex, histology, spontaneous activity, retina, brain mapping, mirror symmetry, corpus callosum}, Mesh = {Animals; Animals, Newborn; Axons; Blindness; Critical Period (Psychology); Disease Models, Animal; Neural Pathways; Rats; Rats, Long-Evans; Visual Cortex; Visual Pathways}, Month = {Sep}, Number = {3}, Pages = {152-6}, Pmc = {PMC3155624}, pmid = {21782890}, Pst = {ppublish}, Title = {Neonatal enucleation during a critical period reduces the precision of cortico-cortical projections in visual cortex}, Volume = {501}, Year = {2011}, url = {papers/Bock_NeurosciLett2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2011.07.005}} @article{Bock:2010, Abstract = {Diffusion tensor imaging (DTI) is a technique that non-invasively provides quantitative measures of water translational diffusion, including fractional anisotropy (FA), that are sensitive to the shape and orientation of cellular elements, such as axons, dendrites and cell somas. For several neurodevelopmental disorders, histopathological investigations have identified abnormalities in the architecture of pyramidal neurons at early stages of cerebral cortex development. To assess the potential capability of DTI to detect neuromorphological abnormalities within the developing cerebral cortex, we compare changes in cortical FA with changes in neuronal architecture and connectivity induced by bilateral enucleation at postnatal day 7 (BEP7) in ferrets. We show here that the visual callosal pattern in BEP7 ferrets is more irregular and occupies a significantly greater cortical area compared to controls at adulthood. To determine whether development of the cerebral cortex is altered in BEP7 ferrets in a manner detectable by DTI, cortical FA was compared in control and BEP7 animals on postnatal day 31. Visual cortex, but not rostrally adjacent non-visual cortex, exhibits higher FA than control animals, consistent with BEP7 animals possessing axonal and dendritic arbors of reduced complexity than age-matched controls. Subsequent to DTI, Golgi-staining and analysis methods were used to identify regions, restricted to visual areas, in which the orientation distribution of neuronal processes is significantly more concentrated than in control ferrets. Together, these findings suggest that DTI can be of utility for detecting abnormalities associated with neurodevelopmental disorders at early stages of cerebral cortical development, and that the neonatally enucleated ferret is a useful animal model system for systematically assessing the potential of this new diagnostic strategy.}, Author = {Bock, Andrew S and Olavarria, Jaime F and Leigland, Lindsey A and Taber, Erin N and Jespersen, Sune N and Kroenke, Christopher D}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:14:04 +0000}, Doi = {10.3389/fnsys.2010.00149}, Journal = {Front Syst Neurosci}, Journal-Full = {Frontiers in systems neuroscience}, Keywords = {visual system, connectivity, visual cortex, neocortex, histology, spontaneous activity, retina, brain mapping, mirror symmetry, corpus callosum}, Pages = {149}, Pmc = {PMC2971465}, pmid = {21048904}, Pst = {epublish}, Title = {Diffusion tensor imaging detects early cerebral cortex abnormalities in neuronal architecture induced by bilateral neonatal enucleation: an experimental model in the ferret}, Volume = {4}, Year = {2010}, url = {papers/Bock_FrontSystNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fnsys.2010.00149}} @article{Ruthazer:2010a, Abstract = {We combined fixed-tissue and time-lapse analyses to investigate the axonal branching phenomena underlying the development of topographically organized ipsilateral projections from area 17 to area 18a in the rat. These complementary approaches allowed us to relate static, large-scale information provided by traditional fixed-tissue analysis to highly dynamic, local, small-scale branching phenomena observed with two-photon time-lapse microscopy in acute slices of visual cortex. Our fixed-tissue data revealed that labeled area 17 fibers invaded area 18a gray matter at topographically restricted sites, reaching superficial layers in significant numbers by postnatal day 6 (P6). Moreover, most parental axons gave rise to only one or occasionally a small number of closely spaced interstitial branches beneath 18a. Our time-lapse data showed that many filopodium-like branches emerged along parental axons in white matter or deep layers in area 18a. Most of these filopodial branches were transient, often disappearing after several minutes to hours of exploratory extension and retraction. These dynamic behaviors decreased significantly from P4, when the projection is first forming, through the second postnatal week, suggesting that the expression of, or sensitivity to, cortical cues promoting new branch addition in the white matter is developmentally down-regulated coincident with gray matter innervation. Together, these data demonstrate that the development of topographically organized corticocortical projections in rats involves extensive exploratory branching along parental axons and invasion of cortex by only a small number of interstitial branches, rather than the widespread innervation of superficial cortical layers by an initially exuberant population of branches.}, Author = {Ruthazer, Edward S and Bachleda, Amelia R and Olavarria, Jaime F}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:14:04 +0000}, Doi = {10.1002/cne.22502}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {currOpinRvw; visual system; connectivity; visual cortex; neocortex; histology; spontaneous activity; retina; brain mapping; mirror symmetry; corpus callosum}, Mesh = {Animals; Animals, Newborn; Axons; Brain Mapping; Cell Differentiation; Microscopy, Video; Neural Pathways; Neuronal Tract-Tracers; Rats; Time Factors; Time-Lapse Imaging; Tissue Fixation; Visual Cortex; Visual Pathways}, Month = {Dec}, Number = {24}, Pages = {4963-79}, pmid = {21031561}, Pst = {ppublish}, Title = {Role of interstitial branching in the development of visual corticocortical connections: a time-lapse and fixed-tissue analysis}, Volume = {518}, Year = {2010}, url = {papers/Ruthazer_JCompNeurol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.22502}} @article{Olavarria:2008, Abstract = {Visual callosal fibers link cortical loci in opposite hemispheres that represent the same visual field but whose locations are not mirror-symmetric with respect to the brain midline. Presence of the eyes from postnatal day 4 (P4) to P6 is required for this map to be specified. We tested the hypothesis that specification of the callosal map requires the activation of N-methyl-D-aspartate receptors (NMDARs). Our results show that blockade of NMDARs with MK-801 during this critical period did not induce obvious abnormalities in callosal connectivity patterns, suggesting that retinal influences do not operate through NMDAR-mediated processes to specify normal callosal topography. In contrast, we found that interfering with NMDAR function either through MK801-induced blockade of NMDARs starting at P6 or neonatal enucleation significantly increases the length of axon branches and total length of arbors, without major effects on the number of branch tips. Our results further suggest that NMDARs act by altering the initial elaboration of arbors rather than by inhibiting a later-occurring remodeling process. Since the callosal map is present by P6, just as axonal branches of simple architecture grow into gray matter, we suggest that regulation of arbor development by NMDAR-mediated processes is important for maintaining the precision of this map.}, Author = {Olavarr{\'\i}a, Jaime F and Laing, Robyn and Hiroi, Ryoko and Lasiene, Jurate}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:14:04 +0000}, Doi = {/S0716-97602008000400007}, Journal = {Biol Res}, Journal-Full = {Biological research}, Keywords = {visual system, connectivity, visual cortex, neocortex, histology, spontaneous activity, retina, brain mapping, mirror symmetry, corpus callosum}, Mesh = {Animals; Animals, Newborn; Axons; Brain Mapping; Corpus Callosum; Dizocilpine Maleate; Excitatory Amino Acid Antagonists; Eye Enucleation; Rats; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate; Visual Pathways}, Number = {4}, Pages = {413-24}, pmid = {19621122}, Pst = {ppublish}, Title = {Topography and axon arbor architecture in the visual callosal pathway: effects of deafferentation and blockade of N-methyl-D-aspartate receptors}, Volume = {41}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/0716-97602008000400007}} @article{Olavarria:2007, Abstract = {Development of the visual callosal projection in rodents goes through an early critical period, from postnatal day (P) 4 to P6, during which retinal input specifies the blueprint for normal topographic connections, and a subsequent period of progressive pathway maturation that is largely complete by the time the eyes open, around P13. This study tests the hypothesis that these developmental stages correlate with age-related changes in the kinetics of synaptic responses mediated by the N-methyl-D-aspartate subclass of glutamate receptors (NMDARs). We used an in vitro slice preparation to perform whole-cell recordings from retrogradely-labeled visual callosal cells, as well from cortical cells with unknown projections. We analyzed age-related changes in the decay time constant of evoked as well as spontaneous excitatory postsynaptic currents mediated by N-methyl-D-aspartate subclass of glutamate receptors (NMDAR-EPSCs) in slices from normal pups and pups enucleated at different postnatal ages. In normal pups we found that the decay time constant of NMDAR-EPSCs increases starting at about P6 and decreases by about P13. In contrast, these changes were not observed in rats enucleated at birth. However, by delaying the age at which enucleation was performed we found that the presence of the eyes until P6, but not until P4, is sufficient for inducing slow NMDAR-EPSC kinetics during the second postnatal week, as observed in normal pups. These results provide evidence that the eyes exert a bidirectional effect on the kinetics of NMDARs: during a P4-P6 critical period, retinal influences induce processes that slow down the kinetics of NMDAR-EPSCs, while, near the age of eye opening, retinal input induces a sudden acceleration of NMDAR-EPSC kinetics. These findings suggest that the retinally-driven processes that specify normal callosal topography during the P4-P6 time window also induce an increase in the decay time constant of NMDAR-EPSCs. This increase in response kinetics may play an important role in the maturation of cortical topographic maps after P6. Using ifenprodil, a noncompetitive NR2B-selective blocker, we obtained evidence that although NR1/NR2B diheteromeric receptors contribute to evoked synaptic responses in both normal and enucleated animals, they are not primarily responsible for either the age-related changes in the kinetics of NMDAR-mediated responses, or the effects that bilateral enucleation has on the kinetics of NMDAR-EPSCs.}, Author = {Olavarria, J F and van Brederode, J F M and Spain, W J}, Date-Added = {2012-12-10 20:12:55 +0000}, Date-Modified = {2012-12-10 20:14:04 +0000}, Doi = {10.1016/j.neuroscience.2007.07.005}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {visual system, connectivity, visual cortex, neocortex, histology, spontaneous activity, retina, brain mapping, mirror symmetry, corpus callosum}, Mesh = {Aging; Animals; Animals, Newborn; Cell Communication; Cell Differentiation; Corpus Callosum; Denervation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Eye Enucleation; Kinetics; Neuronal Plasticity; Organ Culture Techniques; Patch-Clamp Techniques; Presynaptic Terminals; Rats; Rats, Long-Evans; Receptors, N-Methyl-D-Aspartate; Retina; Synaptic Transmission; Visual Cortex; Visual Pathways}, Month = {Sep}, Number = {3}, Pages = {683-99}, pmid = {17706364}, Pst = {ppublish}, Title = {Retinal influences induce bidirectional changes in the kinetics of N-methyl-D-aspartate receptor-mediated responses in striate cortex cells during postnatal development}, Volume = {148}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2007.07.005}} @article{Innocenti:1979a, Author = {Innocenti, G M and Frost, D O}, Date-Added = {2012-12-10 20:06:17 +0000}, Date-Modified = {2012-12-10 20:11:20 +0000}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {visual system; mirror symmetry; Neocortex; visual cortex; activity manipulation; Sensory Deprivation; Spontaneous activity; retina; connectivity; Histological Techniques; Brain Mapping}, Mesh = {Animals; Blindness; Cats; Corpus Callosum; Efferent Pathways; Horseradish Peroxidase; Retrograde Degeneration; Strabismus; Visual Cortex}, Month = {Jul}, Number = {5719}, Pages = {231-4}, pmid = {450139}, Pst = {ppublish}, Title = {Effects of visual experience on the maturation of the efferent system to the corpus callosum}, Volume = {280}, Year = {1979}, url = {papers/Innocenti_Nature1979.pdf}} @article{Nimmervoll:2012, Abstract = {During the pre- and neonatal period, the cerebral cortex reveals distinct patterns of spontaneous synchronized activity, which is critically involved in the formation of early networks and in the regulation of neuronal survival and programmed cell death (apoptosis). During this period, the cortex is also highly vulnerable to inflammation and in humans prenatal infection may have a profound impact on neurodevelopment causing long-term neurological deficits. Using in vitro and in vivo multi-electrode array recordings and quantification of caspase-3 (casp-3)-dependent apoptosis, we demonstrate that lipopolysaccharide-induced inflammation causes rapid alterations in the pattern of spontaneous burst activities, which subsequently leads to an increase in apoptosis. We show that these inflammatory effects are specifically initiated by the microglia-derived pro-inflammatory cytokine tumor necrosis factor α and the chemokine macrophage inflammatory protein 2. Our data demonstrate that inflammation-induced modifications in spontaneous network activities influence casp-3-dependent cell death in the developing cerebral cortex.}, Author = {Nimmervoll, Birgit and White, Robin and Yang, Jenq-Wei and An, Shuming and Henn, Christopher and Sun, Jyh-Jang and Luhmann, Heiko J}, Date-Added = {2012-11-20 14:55:43 +0000}, Date-Modified = {2012-11-20 15:00:14 +0000}, Doi = {10.1093/cercor/bhs156}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {genes; self organization; Competitive Behavior; optical imaging; optical physiology; toread; wholeBrain; Somatosensory Cortex; thalamus; barrels; Mouse; development; synchrony; oscillations; microglia}, Month = {Jun}, pmid = {22700645}, Pst = {aheadofprint}, Title = {LPS-Induced Microglial Secretion of TNFα Increases Activity-Dependent Neuronal Apoptosis in the Neonatal Cerebral Cortex}, Year = {2012}, url = {papers/Nimmervoll_CerebCortex2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhs156}} @article{Yang:2012a, Abstract = {Neocortical areas are organized in columns, which form the basic structural and functional modules of intracortical information processing. Using voltage-sensitive dye imaging and simultaneous multi-channel extracellular recordings in the barrel cortex of newborn rats in vivo, we found that spontaneously occurring and whisker stimulation-induced gamma bursts followed by longer lasting spindle bursts were topographically organized in functional cortical columns already at the day of birth. Gamma bursts synchronized a cortical network of 300-400 µm in diameter and were coherent with gamma activity recorded simultaneously in the thalamic ventral posterior medial (VPM) nucleus. Cortical gamma bursts could be elicited by focal electrical stimulation of the VPM. Whisker stimulation-induced spindle and gamma bursts and the majority of spontaneously occurring events were profoundly reduced by the local inactivation of the VPM, indicating that the thalamus is important to generate these activity patterns. Furthermore, inactivation of the barrel cortex with lidocaine reduced the gamma activity in the thalamus, suggesting that a cortico-thalamic feedback loop modulates this early thalamic network activity.}, Author = {Yang, Jenq-Wei and An, Shuming and Sun, Jyh-Jang and Reyes-Puerta, Vicente and Kindler, Jennifer and Berger, Thomas and Kilb, Werner and Luhmann, Heiko J}, Date-Added = {2012-11-20 14:55:31 +0000}, Date-Modified = {2012-11-20 14:59:37 +0000}, Doi = {10.1093/cercor/bhs103}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {genes; self organization; Competitive Behavior; optical imaging; optical physiology; toread; wholeBrain; Somatosensory Cortex; thalamus; barrels; Mouse; development; synchrony; oscillations}, Month = {May}, pmid = {22593243}, Pst = {aheadofprint}, Title = {Thalamic Network Oscillations Synchronize Ontogenetic Columns in the Newborn Rat Barrel Cortex}, Year = {2012}, url = {papers/Yang_CerebCortex2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhs103}} @article{Blanton:1990, Abstract = {Before synapses form in embryonic turtle cerebral cortex, an endogenous neurotransmitter activates N-methyl-D-aspartate (NMDA) channels on neurons in the cortical plate. Throughout cortical development, these channels exhibit voltage-dependent Mg2+ blockade and are antagonized by D-2-amino-5-phosphonovaleric acid, a selective NMDA receptor antagonist. The activation in situ of these nonsynaptic NMDA channels demonstrates a potential physiological substrate for control of early neuronal differentiation.}, Author = {Blanton, M G and Lo Turco, J J and Kriegstein, A R}, Date-Added = {2012-11-15 22:04:30 +0000}, Date-Modified = {2012-11-15 22:05:41 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Activity-development; NMDA; Glutamate; Spontaneous activity; Calcium Signaling; Electrophysiology; Turtles; embryology; physiology}, Mesh = {2-Amino-5-phosphonovalerate; Animals; Axons; Cell Differentiation; Cerebral Cortex; Electric Conductivity; Embryo, Nonmammalian; Glutamates; Glutamic Acid; Magnesium; Neurons; Neurotransmitter Agents; Receptors, N-Methyl-D-Aspartate; Turtles}, Month = {Oct}, Number = {20}, Pages = {8027-30}, Pmc = {PMC54885}, pmid = {1978317}, Pst = {ppublish}, Title = {Endogenous neurotransmitter activates N-methyl-D-aspartate receptors on differentiating neurons in embryonic cortex}, Volume = {87}, Year = {1990}} @article{Bassett:2006a, Abstract = {Many complex networks have a small-world topology characterized by dense local clustering or cliquishness of connections between neighboring nodes yet a short path length between any (distant) pair of nodes due to the existence of relatively few long-range connections. This is an attractive model for the organization of brain anatomical and functional networks because a small-world topology can support both segregated/specialized and distributed/integrated information processing. Moreover, small-world networks are economical, tending to minimize wiring costs while supporting high dynamical complexity. The authors introduce some of the key mathematical concepts in graph theory required for small-world analysis and review how these methods have been applied to quantification of cortical connectivity matrices derived from anatomical tract-tracing studies in the macaque monkey and the cat. The evolution of small-world networks is discussed in terms of a selection pressure to deliver cost-effective information-processing systems. The authors illustrate how these techniques and concepts are increasingly being applied to the analysis of human brain functional networks derived from electroencephalography/magnetoencephalography and fMRI experiments. Finally, the authors consider the relevance of small-world models for understanding the emergence of complex behaviors and the resilience of brain systems to pathological attack by disease or aberrant development. They conclude that small-world models provide a powerful and versatile approach to understanding the structure and function of human brain systems.}, Author = {Bassett, Danielle Smith and Bullmore, Ed}, Date-Added = {2012-11-15 13:34:38 +0000}, Date-Modified = {2012-11-15 13:34:45 +0000}, Doi = {10.1177/1073858406293182}, Journal = {Neuroscientist}, Journal-Full = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, Keywords = {network; technique; Methods; review literature; computation biology; Theoretical; graph theory; human; fmri; Software; toread}, Mesh = {Animals; Brain; Brain Mapping; Humans; Models, Neurological; Nerve Net}, Month = {Dec}, Number = {6}, Pages = {512-23}, pmid = {17079517}, Pst = {ppublish}, Title = {Small-world brain networks}, Volume = {12}, Year = {2006}, url = {papers/Bassett_Neuroscientist2006.pdf}} @article{Bullmore:2009, Abstract = {Recent developments in the quantitative analysis of complex networks, based largely on graph theory, have been rapidly translated to studies of brain network organization. The brain's structural and functional systems have features of complex networks--such as small-world topology, highly connected hubs and modularity--both at the whole-brain scale of human neuroimaging and at a cellular scale in non-human animals. In this article, we review studies investigating complex brain networks in diverse experimental modalities (including structural and functional MRI, diffusion tensor imaging, magnetoencephalography and electroencephalography in humans) and provide an accessible introduction to the basic principles of graph theory. We also highlight some of the technical challenges and key questions to be addressed by future developments in this rapidly moving field.}, Author = {Bullmore, Ed and Sporns, Olaf}, Date-Added = {2012-11-15 13:33:26 +0000}, Date-Modified = {2014-08-05 13:06:00 +0000}, Doi = {10.1038/nrn2575}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {network; technique; Methods; review literature; computation biology; Theoretical; graph theory; human; fmri; Software}, Mesh = {Animals; Brain; Brain Mapping; Computer Graphics; Electroencephalography; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetoencephalography; Nerve Net; Neural Networks (Computer)}, Month = {Mar}, Number = {3}, Pages = {186-98}, pmid = {19190637}, Pst = {ppublish}, Title = {Complex brain networks: graph theoretical analysis of structural and functional systems}, Volume = {10}, Year = {2009}, url = {papers/Bullmore_NatRevNeurosci2009.pdf}} @article{Lynall:2010, Abstract = {Schizophrenia has often been conceived as a disorder of connectivity between components of large-scale brain networks. We tested this hypothesis by measuring aspects of both functional connectivity and functional network topology derived from resting-state fMRI time series acquired at 72 cerebral regions over 17 min from 15 healthy volunteers (14 male, 1 female) and 12 people diagnosed with schizophrenia (10 male, 2 female). We investigated between-group differences in strength and diversity of functional connectivity in the 0.06-0.125 Hz frequency interval, and some topological properties of undirected graphs constructed from thresholded interregional correlation matrices. In people with schizophrenia, strength of functional connectivity was significantly decreased, whereas diversity of functional connections was increased. Topologically, functional brain networks had reduced clustering and small-worldness, reduced probability of high-degree hubs, and increased robustness in the schizophrenic group. Reduced degree and clustering were locally significant in medial parietal, premotor and cingulate, and right orbitofrontal cortical nodes of functional networks in schizophrenia. Functional connectivity and topological metrics were correlated with each other and with behavioral performance on a verbal fluency task. We conclude that people with schizophrenia tend to have a less strongly integrated, more diverse profile of brain functional connectivity, associated with a less hub-dominated configuration of complex brain functional networks. Alongside these behaviorally disadvantageous differences, however, brain networks in the schizophrenic group also showed a greater robustness to random attack, pointing to a possible benefit of the schizophrenia connectome, if less extremely expressed.}, Author = {Lynall, Mary-Ellen and Bassett, Danielle S and Kerwin, Robert and McKenna, Peter J and Kitzbichler, Manfred and Muller, Ulrich and Bullmore, Ed}, Date-Added = {2012-11-14 22:00:52 +0000}, Date-Modified = {2014-01-27 14:57:50 +0000}, Doi = {10.1523/JNEUROSCI.0333-10.2010}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {connectivity; Schizophrenia; human; fmri; Functional Laterality; network; graph theory; Technique; grant; wholeBrain; Schizophrenia}, Mesh = {Adult; Brain; Brain Mapping; Cognition; Female; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Models, Neurological; Nerve Net; Neural Pathways; Neuropsychological Tests; Principal Component Analysis; Schizophrenia}, Month = {Jul}, Number = {28}, Pages = {9477-87}, Pmc = {PMC2914251}, pmid = {20631176}, Pst = {ppublish}, Title = {Functional connectivity and brain networks in schizophrenia}, Volume = {30}, Year = {2010}, url = {papers/Lynall_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0333-10.2010}} @article{Karlsgodt:2008, Abstract = {Schizophrenia has been thought of as a disorder of reduced functional and structural connectivity. Recent advances in neuroimaging techniques such as functional magnetic resonance imaging, structural magnetic resonance imaging, diffusion tensor imaging, and small animal imaging have advanced our ability to investigate this hypothesis. Moreover, the power of longitudinal designs possible with these noninvasive techniques enable the study of not just how connectivity is disrupted in schizophrenia, but when this disruption emerges during development. This article reviews genetic and neurodevelopmental influences on structural and functional connectivity in human populations with or at risk for schizophrenia and in animal models of the disorder. We conclude that the weight of evidence across these diverse lines of inquiry points to a developmental disruption of neural connectivity in schizophrenia and that this disrupted connectivity likely involves susceptibility genes that affect processes involved in establishing intra- and interregional connectivity.}, Author = {Karlsgodt, Katherine H and Sun, Daqiang and Jimenez, Amy M and Lutkenhoff, Evan S and Willhite, Rachael and van Erp, Theo G M and Cannon, Tyrone D}, Date-Added = {2012-11-14 21:29:25 +0000}, Date-Modified = {2012-11-14 21:30:17 +0000}, Doi = {10.1017/S095457940800062X}, Journal = {Dev Psychopathol}, Journal-Full = {Development and psychopathology}, Keywords = {Schizophrenia; neurological disorder; Cognition; Cognition Disorders; Functional Laterality; asymmetry; mirror symmetry; fMRI; connectivity; human; mouse}, Mesh = {Adolescent; Adult; Animals; Brain; Brain Mapping; Child; Child Development; Cognition Disorders; Disease Models, Animal; Environment; Genetic Predisposition to Disease; Genotype; Humans; Magnetic Resonance Imaging; Models, Neurological; Neural Conduction; Neurons; Risk Factors; Schizophrenia; Synapses; Young Adult}, Number = {4}, Pages = {1297-327}, pmid = {18838043}, Pst = {ppublish}, Title = {Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia}, Volume = {20}, Year = {2008}, url = {papers/Karlsgodt_DevPsychopathol2008.pdf}} @article{Bressler:2010, Abstract = {An understanding of how the human brain produces cognition ultimately depends on knowledge of large-scale brain organization. Although it has long been assumed that cognitive functions are attributable to the isolated operations of single brain areas, we demonstrate that the weight of evidence has now shifted in support of the view that cognition results from the dynamic interactions of distributed brain areas operating in large-scale networks. We review current research on structural and functional brain organization, and argue that the emerging science of large-scale brain networks provides a coherent framework for understanding of cognition. Critically, this framework allows a principled exploration of how cognitive functions emerge from, and are constrained by, core structural and functional networks of the brain.}, Author = {Bressler, Steven L and Menon, Vinod}, Date-Added = {2012-11-14 21:24:24 +0000}, Date-Modified = {2012-11-14 21:28:09 +0000}, Doi = {10.1016/j.tics.2010.04.004}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {toread; resting state; default mode network; connectivity; connectome; human; fMRI; function; Functional Laterality; Technique; Methods; Computational Biology; graph theory; network}, Mesh = {Animals; Brain; Brain Mapping; Cognition; Humans; Neural Pathways; Psychopathology}, Month = {Jun}, Number = {6}, Pages = {277-90}, pmid = {20493761}, Pst = {ppublish}, Title = {Large-scale brain networks in cognition: emerging methods and principles}, Volume = {14}, Year = {2010}, url = {papers/Bressler_TrendsCognSci2010.pdf}} @article{Menon:2011, Abstract = {The science of large-scale brain networks offers a powerful paradigm for investigating cognitive and affective dysfunction in psychiatric and neurological disorders. This review examines recent conceptual and methodological developments which are contributing to a paradigm shift in the study of psychopathology. I summarize methods for characterizing aberrant brain networks and demonstrate how network analysis provides novel insights into dysfunctional brain architecture. Deficits in access, engagement and disengagement of large-scale neurocognitive networks are shown to play a prominent role in several disorders including schizophrenia, depression, anxiety, dementia and autism. Synthesizing recent research, I propose a triple network model of aberrant saliency mapping and cognitive dysfunction in psychopathology, emphasizing the surprising parallels that are beginning to emerge across psychiatric and neurological disorders.}, Author = {Menon, Vinod}, Date-Added = {2012-11-14 21:15:29 +0000}, Date-Modified = {2012-11-14 21:16:16 +0000}, Doi = {10.1016/j.tics.2011.08.003}, Journal = {Trends Cogn Sci}, Journal-Full = {Trends in cognitive sciences}, Keywords = {toread; connectivity; connectome; function; Functional Laterality; resting state; default mode network; human; neuroimaging; fMRI; Cognition; Cognition Disorders; neurological disorder}, Mesh = {Brain; Humans; Models, Neurological; Nerve Net; Psychopathology}, Month = {Oct}, Number = {10}, Pages = {483-506}, pmid = {21908230}, Pst = {ppublish}, Title = {Large-scale brain networks and psychopathology: a unifying triple network model}, Volume = {15}, Year = {2011}, url = {papers/Menon_TrendsCognSci2011.pdf}} @article{Courchesne:2005, Abstract = {Although it has long been thought that frontal lobe abnormality must play an important part in generating the severe impairment in higher-order social, emotional and cognitive functions in autism, only recently have studies identified developmentally early frontal lobe defects. At the microscopic level, neuroinflammatory reactions involving glial activation, migration defects and excess cerebral neurogenesis and/or defective apoptosis might generate frontal neural pathology early in development. It is hypothesized that these abnormal processes cause malformation and thus malfunction of frontal minicolumn microcircuitry. It is suggested that connectivity within frontal lobe is excessive, disorganized and inadequately selective, whereas connectivity between frontal cortex and other systems is poorly synchronized, weakly responsive and information impoverished. Increased local but reduced long-distance cortical-cortical reciprocal activity and coupling would impair the fundamental frontal function of integrating information from widespread and diverse systems and providing complex context-rich feedback, guidance and control to lower-level systems.}, Author = {Courchesne, Eric and Pierce, Karen}, Date-Added = {2012-11-14 20:03:57 +0000}, Date-Modified = {2012-11-14 20:05:51 +0000}, Doi = {10.1016/j.conb.2005.03.001}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Autistic Disorder; autism; connectivity; human; mirror symmetry; neurological disorder; function; Frontal Lobe; Neocortex; Cerebral Cortex}, Mesh = {Autistic Disorder; Frontal Lobe; Humans; Nerve Net}, Month = {Apr}, Number = {2}, Pages = {225-30}, pmid = {15831407}, Pst = {ppublish}, Title = {Why the frontal cortex in autism might be talking only to itself: local over-connectivity but long-distance disconnection}, Volume = {15}, Year = {2005}, url = {papers/Courchesne_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.03.001}} @article{Desgent:2012, Abstract = {Early loss of a given sensory input in mammals causes anatomical and functional modifications in the brain via a process called cross-modal plasticity. In the past four decades, several animal models have illuminated our understanding of the biological substrates involved in cross-modal plasticity. Progressively, studies are now starting to emphasise on cell-specific mechanisms that may be responsible for this intermodal sensory plasticity. Inhibitory interneurons expressing γ-aminobutyric acid (GABA) play an important role in maintaining the appropriate dynamic range of cortical excitation, in critical periods of developmental plasticity, in receptive field refinement, and in treatment of sensory information reaching the cerebral cortex. The diverse interneuron population is very sensitive to sensory experience during development. GABAergic neurons are therefore well suited to act as a gate for mediating cross-modal plasticity. This paper attempts to highlight the links between early sensory deprivation, cortical GABAergic interneuron alterations, and cross-modal plasticity, discuss its implications, and further provide insights for future research in the field.}, Author = {Desgent, S{\'e}bastien and Ptito, Maurice}, Date-Added = {2012-11-14 19:31:01 +0000}, Date-Modified = {2012-11-14 19:33:09 +0000}, Doi = {10.1155/2012/590725}, Journal = {Neural Plast}, Journal-Full = {Neural plasticity}, Keywords = {GABA; interneurons; development; Cerebral Cortex; Neocortex; visual cortex; visual system; multimodal; vision; Sensory Deprivation; plasticity; structural remodeling; Structure-Activity Relationship; Spontaneous activity}, Pages = {590725}, Pmc = {PMC3377178}, pmid = {22720175}, Pst = {ppublish}, Title = {Cortical GABAergic interneurons in cross-modal plasticity following early blindness}, Volume = {2012}, Year = {2012}, url = {papers/Desgent_NeuralPlast2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1155/2012/590725}} @article{Baumann:2012, Author = {Baumann, Kim}, Date-Added = {2012-11-14 18:49:22 +0000}, Date-Modified = {2012-11-14 18:50:14 +0000}, Doi = {10.1038/nrm3456}, Journal = {Nat Rev Mol Cell Biol}, Journal-Full = {Nature reviews. Molecular cell biology}, Keywords = {mirror symmetry; asymmetry;development; patterning;Gene Expression;toread}, Month = {Nov}, Number = {11}, Pages = {682-3}, pmid = {23034454}, Pst = {ppublish}, Title = {Development: Knowing left from right}, Volume = {13}, Year = {2012}, url = {papers/Baumann_NatRevMolCellBiol2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrm3456}} @article{Nakamura:2012, Abstract = {The left-right (LR) asymmetry of visceral organs is fundamental to their function and position within the body. Over the past decade or so, the molecular mechanisms underlying the establishment of such LR asymmetry have been revealed in many vertebrate and invertebrate model organisms. These studies have identified a gene network that contributes to this process and is highly conserved from sea urchin to mouse. By contrast, some specific steps of the process, such as the symmetry-breaking event and situs-specific organogenesis, appear to have diverged during evolution. Here, we summarize the common and divergent mechanisms by which LR asymmetry is established in vertebrates.}, Author = {Nakamura, Tetsuya and Hamada, Hiroshi}, Date-Added = {2012-11-14 18:41:32 +0000}, Date-Modified = {2012-11-14 18:41:37 +0000}, Doi = {10.1242/dev.061606}, Journal = {Development}, Journal-Full = {Development (Cambridge, England)}, Keywords = {development; mirror symmetry; asymmetry; Gene Expression; patterning; toread}, Mesh = {Animals; Body Patterning; Cell Movement; Gene Expression Regulation, Developmental; Invertebrates; Mice; Sea Urchins; Vertebrates}, Month = {Sep}, Number = {18}, Pages = {3257-62}, pmid = {22912409}, Pst = {ppublish}, Title = {Left-right patterning: conserved and divergent mechanisms}, Volume = {139}, Year = {2012}, url = {papers/Nakamura_Development2012.pdf}} @article{Vandenberg:2010, Abstract = {Consistent laterality is a crucial aspect of embryonic development, physiology, and behavior. While strides have been made in understanding unilaterally expressed genes and the asymmetries of organogenesis, early mechanisms are still poorly understood. One popular model centers on the structure and function of motile cilia and subsequent chiral extracellular fluid flow during gastrulation. Alternative models focus on intracellular roles of the cytoskeleton in driving asymmetries of physiological signals or asymmetric chromatid segregation, at much earlier stages. All three models trace the origin of asymmetry back to the chirality of cytoskeletal organizing centers, but significant controversy exists about how this intracellular chirality is amplified onto cell fields. Analysis of specific predictions of each model and crucial recent data on new mutants suggest that ciliary function may not be a broadly conserved, initiating event in left-right patterning. Many questions about embryonic left-right asymmetry remain open, offering fascinating avenues for further research in cell, developmental, and evolutionary biology.}, Author = {Vandenberg, Laura N and Levin, Michael}, Date-Added = {2012-11-14 18:39:32 +0000}, Date-Modified = {2013-09-25 20:54:06 +0000}, Doi = {10.1002/dvdy.22450}, Journal = {Dev Dyn}, Journal-Full = {Developmental dynamics : an official publication of the American Association of Anatomists}, Keywords = {development; mirror symmetry; asymmetry; Gene Expression; patterning; cerebral cortex; lateralization; asymmetry; hemisphere; Grants; mouse; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb; language}, Mesh = {Animals; Body Patterning; Embryonic Development; Humans; Models, Biological}, Month = {Dec}, Number = {12}, Pages = {3131-46}, pmid = {21031419}, Pst = {ppublish}, Title = {Far from solved: a perspective on what we know about early mechanisms of left-right asymmetry}, Volume = {239}, Year = {2010}, url = {papers/Vandenberg_DevDyn2010.pdf}} @article{Yost:1998, Abstract = {Bilateran animals have external bilateral symmetry along the dorsoventral (DV) and anteroposterior (AP) axes. Internal left-right asymmetries appear to be consistently aligned along the left-right (LR) axis with respect to the other axes. Left-right development is most apparent in the directional looping of the cardiac tube, the coiling and placement of the intestines, the positioning of internal organs such as liver, gallbladder, pancreas, and stomach. In addition, there are obvious morphological asymmetries in the brains of some vertebrates and functional left-right asymmetries in the activities of the brain, as assessed by psychological testing, MRI, and the analysis of lesions. There are several fundamental questions: What are the origins of the left-right axis, and are they highly conserved across metazoans? Once the left-right axis is established by the initial breaking of bilateral symmetry, what is the genetic pathway that perpetrates left-right development? What are the cellular and tissue mechanics that lead to morphogenesis during, for example, the looping of the cardiac tube, the coiling of the gut, or asymmetric brain development? Finally, do the asymmetric developmental pathways of each organ system take register from the same initial event that establishes the left-right axis, or are there separate mechanisms that orient heart, gut, and brain left-right asymmetry with respect to the DV and AP axes? These questions are beginning to be experimentally addressed, and papers in this issue of Developmental Genetics make contributions to several aspects in the burgeoning field of left-right development. Recent reviews have summarized the emerging genes and pathways in vertebrate left-right development [Wood, 1997; Harvey, 1998; Ramsdell and Yost, 1998]. Here, I give an overview of the contributions in this issue to the fundamental questions in left-right development.}, Author = {Yost, H J}, Date-Added = {2012-11-14 17:37:21 +0000}, Date-Modified = {2012-11-14 17:40:53 +0000}, Doi = {10.1002/(SICI)1520-6408(1998)23:3<159::AID-DVG1>3.0.CO;2-1}, Journal = {Dev Genet}, Journal-Full = {Developmental genetics}, Keywords = {asymmetry; lateralization; Cerebral Cortex; callosal; mirror symmetry; toread}, Mesh = {Animals; Body Patterning; Brain; Functional Laterality; Humans; Mesoderm; Stereoisomerism}, Number = {3}, Pages = {159-63}, pmid = {9842710}, Pst = {ppublish}, Title = {Left-right development from embryos to brains}, Volume = {23}, Year = {1998}, url = {papers/Yost_DevGenet1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1520-6408(1998)23:3%3C159::AID-DVG1%3E3.0.CO;2-1}} @article{Borodinsky:2004, Abstract = {Neurotransmitters are essential for interneuronal signalling, and the specification of appropriate transmitters in differentiating neurons has been related to intrinsic neuronal identity and to extrinsic signalling proteins. Here we show that altering the distinct patterns of Ca2+ spike activity spontaneously generated by different classes of embryonic spinal neurons in vivo changes the transmitter that neurons express without affecting the expression of markers of cell identity. Regulation seems to be homeostatic: suppression of activity leads to an increased number of neurons expressing excitatory transmitters and a decreased number of neurons expressing inhibitory transmitters; the reverse occurs when activity is enhanced. The imposition of specific spike frequencies in vitro does not affect labels of cell identity but again specifies the expression of transmitters that are inappropriate for the markers they express, during an early critical period. The results identify a new role of patterned activity in development of the central nervous system.}, Author = {Borodinsky, Laura N and Root, Cory M and Cronin, Julia A and Sann, Sharon B and Gu, Xiaonan and Spitzer, Nicholas C}, Date-Added = {2012-11-13 16:08:31 +0000}, Date-Modified = {2012-11-14 16:34:47 +0000}, Doi = {10.1038/nature02518}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Spontaneous activity; development; Activity-development; Gene Expression; Transcription Factors; Calcium Signaling; Neurophysiology;xenopus; activity manipulation; Differentiation; Transmission; Neurotransmitters}, Mesh = {Action Potentials; Animals; Calcium; Calcium Signaling; Cell Differentiation; Cells, Cultured; Gene Expression Regulation; Homeostasis; Humans; Neurons; Neurotransmitter Agents; Organ Specificity; Phenotype; Potassium Channels, Inwardly Rectifying; Rats; Sodium Channels; Spinal Cord; Xenopus laevis}, Month = {Jun}, Number = {6991}, Pages = {523-30}, pmid = {15175743}, Pst = {ppublish}, Title = {Activity-dependent homeostatic specification of transmitter expression in embryonic neurons}, Volume = {429}, Year = {2004}, url = {papers/Borodinsky_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature02518}} @article{Marek:2010, Abstract = {Neuronal differentiation is accomplished through cascades of intrinsic genetic factors initiated in neuronal progenitors by external gradients of morphogens. Activity has been thought to be important only late in development, but recent evidence suggests that activity also regulates early neuronal differentiation. Activity in post-mitotic neurons before synapse formation can regulate phenotypic specification, including neurotransmitter choice, but the mechanisms are not clear. We identified a mechanism that links endogenous calcium spike activity with an intrinsic genetic pathway to specify neurotransmitter choice in neurons in the dorsal embryonic spinal cord of Xenopus tropicalis. Early activity modulated transcription of the GABAergic/glutamatergic selection gene tlx3 through a variant cAMP response element (CRE) in its promoter. The cJun transcription factor bound to this CRE site, modulated transcription and regulated neurotransmitter phenotype via its transactivation domain. Calcium signaled through cJun N-terminal phosphorylation, which integrated activity-dependent and intrinsic neurotransmitter specification. This mechanism provides a basis for early activity to regulate genetic pathways at critical decision points, switching the phenotype of developing neurons.}, Author = {Marek, Kurt W and Kurtz, Lisa M and Spitzer, Nicholas C}, Date-Added = {2012-11-13 16:07:23 +0000}, Date-Modified = {2012-11-13 16:08:05 +0000}, Doi = {10.1038/nn.2582}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Activity-development;Spontaneous activity;development;10 circuit formation;Synapses;Electric Conductivity;Cell Differentiation;21 Neurophysiology;Animals;Brain;Neurons; Gene Expression; Transcription Factors; Activity-development; Structure-Activity Relationship; axon guidance; cell migration;Xenopus}, Mesh = {Animals; Base Sequence; Calcium; Calcium Signaling; Electrophoretic Mobility Shift Assay; Gene Expression; Gene Expression Regulation, Developmental; Homeodomain Proteins; Immunohistochemistry; In Situ Hybridization; Molecular Sequence Data; Neurogenesis; Neurons; Neurotransmitter Agents; Promoter Regions, Genetic; Proto-Oncogene Proteins c-jun; Response Elements; Reverse Transcriptase Polymerase Chain Reaction; Xenopus; Xenopus Proteins}, Month = {Aug}, Number = {8}, Pages = {944-50}, Pmc = {PMC2910808}, pmid = {20581840}, Pst = {ppublish}, Title = {cJun integrates calcium activity and tlx3 expression to regulate neurotransmitter specification}, Volume = {13}, Year = {2010}, url = {papers/Marek_NatNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2582}} @article{Mire:2012, Abstract = {Developing axons must control their growth rate to follow the appropriate pathways and establish specific connections. However, the regulatory mechanisms involved remain elusive. By combining live imaging with transplantation studies in mice, we found that spontaneous calcium activity in the thalamocortical system and the growth rate of thalamocortical axons were developmentally and intrinsically regulated. Indeed, the spontaneous activity of thalamic neurons governed axon growth and extension through the cortex in vivo. This activity-dependent modulation of growth was mediated by transcriptional regulation of Robo1 through an NF-κB binding site. Disruption of either the Robo1 or Slit1 genes accelerated the progression of thalamocortical axons in vivo, and interfering with Robo1 signaling restored normal axon growth in electrically silent neurons. Thus, modifications to spontaneous calcium activity encode a switch in the axon outgrowth program that allows the establishment of specific neuronal connections through the transcriptional regulation of Slit1 and Robo1 signaling.}, Author = {Mire, Erik and Mezzera, Cecilia and Leyva-D{\'\i}az, Eduardo and Paternain, Ana V and Squarzoni, Paola and Bluy, Lisa and Castillo-Paterna, Mar and L{\'o}pez, Mar{\'\i}a Jos{\'e} and Peregr{\'\i}n, Sandra and Tessier-Lavigne, Marc and Garel, Sonia and Galcer{\'a}n, Joan and Lerma, Juan and L{\'o}pez-Bendito, Guillermina}, Date-Added = {2012-11-13 13:49:58 +0000}, Date-Modified = {2012-11-13 15:54:38 +0000}, Doi = {10.1038/nn.3160}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Spontaneous activity; development; Activity-development; activity manipulation; Structure-Activity Relationship; structural remodeling; axon guidance; synapse formation; Synaptic Transmission; mouse; thalamus; Cerebral Cortex; Neocortex; optical imaging; Transcription Factors; Gene Expression}, Mesh = {Animals; Axons; Calcium; Calcium Signaling; Cerebral Cortex; Female; Gene Expression Regulation, Developmental; Mice; Nerve Tissue Proteins; Receptors, Immunologic; Thalamus}, Month = {Aug}, Number = {8}, Pages = {1134-43}, pmid = {22772332}, Pst = {epublish}, Title = {Spontaneous activity regulates Robo1 transcription to mediate a switch in thalamocortical axon growth}, Volume = {15}, Year = {2012}, url = {papers/Mire_NatNeurosci2012.pdf}} @article{Bouwman:2004, Abstract = {Outgrowing axons in the developing nervous system secrete neurotransmitters and neuromodulatory substances, which is considered to stimulate synaptogenesis. However, some synapses develop independent of presynaptic secretion. To investigate the role of secretion in synapse formation and maintenance in vivo, we quantified synapses and their morphology in the neocortical marginal zone of munc18-1 deficient mice which lack both evoked and spontaneous secretion [Science 287 (2000) 864]. Histochemical analyses at embryonic day 18 (E18) showed that the overall organization of the neocortex and the number of cells were similar in mutants and controls. Western blot analysis revealed equal concentrations of pre- and post-synaptic marker proteins in mutants and controls and immunocytochemical analyses indicated that these markers were targeted to the neuropil of the synaptic layer in the mutant neocortex. Electron microscopy revealed that at E16 immature synapses had formed both in mutants and controls. These synapses had a similar synapse diameter, active zone length and contained similar amounts of synaptic vesicles, which were immuno-positive for two synaptic vesicle markers. However, these synapses were three times less abundant in the mutant. Two days later, E18, synapses in the controls had more total and docked vesicles, but not in the mutant. Furthermore, synapses were now five times less abundant in the mutant. In both mutant and controls, synapse-like structures were observed with irregular shaped vesicles on both sides of the synaptic cleft. These 'multivesicular structures' were immuno-positive for synaptic vesicle markers and were four times more abundant in the mutant. We conclude that in the absence of presynaptic secretion immature synapses with a normal morphology form, but fewer in number. These secretion-deficient synapses might fail to mature and instead give rise to multivesicular structures. These two observations suggest that secretion of neurotransmitters and neuromodulatory substances is required for synapse maintenance, not for synaptogenesis. Multivesicular structures may develop out of unstable synapses.}, Author = {Bouwman, J and Maia, A S and Camoletto, P G and Posthuma, G and Roubos, E W and Oorschot, V M J and Klumperman, J and Verhage, M}, Date-Added = {2012-11-12 22:33:08 +0000}, Date-Modified = {2012-11-12 22:34:24 +0000}, Doi = {10.1016/j.neuroscience.2004.03.027}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {Anatomy; activity manipulation; transgenic; mouse; synapse formation; axon guidance; Structure-Activity Relationship; Activity-development; development; Spontaneous activity; Synaptic Transmission}, Mesh = {Animals; Female; Immunohistochemistry; Mice; Mice, Mutant Strains; Microscopy, Electron; Munc18 Proteins; Neocortex; Nerve Tissue Proteins; Neurons; Pregnancy; Synapses; Synaptic Transmission; Synaptic Vesicles; Vesicular Transport Proteins}, Number = {1}, Pages = {115-26}, pmid = {15145078}, Pst = {ppublish}, Title = {Quantification of synapse formation and maintenance in vivo in the absence of synaptic release}, Volume = {126}, Year = {2004}, url = {papers/Bouwman_Neuroscience2004.pdf}} @article{Yamamoto:2002, Abstract = {During development of the central nervous system, growth cones navigate along specific pathways, recognize their targets and then form synaptic connections by elaborating terminal arbors. To date, a number of developmental and in vitro studies have characterized the nature of the guidance cues that underlie various types of axonal behavior, from initial outgrowth to synapse formation, including pathway selection, polarized growth, orientated growth, termination and branching. New approaches in molecular biology have identified several types of guidance cues, most of which are likely to act as local cues. Moreover, recent studies have indicated that axonal responsiveness to guidance cues changes dynamically, which appears to be elicited by environmental factors encountered by the navigating growth cones. This article addresses what molecular cues are responsible for guidance mechanisms including axonal responsiveness, focusing on axonal behavior in the developmental stages.}, Author = {Yamamoto, Nobuhiko and Tamada, Atsushi and Murakami, Fujio}, Date-Added = {2012-11-12 22:31:49 +0000}, Date-Modified = {2012-11-12 22:33:00 +0000}, Journal = {Prog Neurobiol}, Journal-Full = {Progress in neurobiology}, Keywords = {review; toread; Structure-Activity Relationship; Spontaneous activity; axon guidance; development; Activity-development; in vitro; Thalamus; Cerebral Cortex; Neocortex}, Mesh = {Axons; Brain; Cell Communication; Cell Differentiation; Growth Cones; Nerve Growth Factors; Nerve Tissue Proteins; Neural Pathways; Neuronal Plasticity; Neurons; Signal Transduction; Synapses}, Month = {Dec}, Number = {6}, Pages = {393-407}, pmid = {12576293}, Pst = {ppublish}, Title = {Wiring of the brain by a range of guidance cues}, Volume = {68}, Year = {2002}, url = {papers/Yamamoto_ProgNeurobiol2002.pdf}} @article{Mason:2009, Author = {Mason, Carol}, Date-Added = {2012-11-08 22:33:58 +0000}, Date-Modified = {2012-11-08 22:34:41 +0000}, Doi = {10.1523/JNEUROSCI.4648-09.2009}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread; development; review literature}, Mesh = {Animals; Brain; Developmental Biology; History, 20th Century; History, 21st Century; Humans; Neurons; Neurosciences}, Month = {Oct}, Number = {41}, Pages = {12735-47}, pmid = {19828784}, Pst = {ppublish}, Title = {The development of developmental neuroscience}, Volume = {29}, Year = {2009}, url = {papers/Mason_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4648-09.2009}} @article{Sato:2012, Abstract = {Electrode recordings and imaging studies have revealed that localized visual stimuli elicit waves of activity that travel across primary visual cortex. Traveling waves are present also during spontaneous activity, but they can be greatly reduced by widespread and intensive visual stimulation. In this Review, we summarize the evidence in favor of these traveling waves. We suggest that their substrate may lie in long-range horizontal connections and that their functional role may involve the integration of information over large regions of space.}, Author = {Sato, Tatsuo K and Nauhaus, Ian and Carandini, Matteo}, Date-Added = {2012-11-08 22:32:50 +0000}, Date-Modified = {2012-11-08 22:33:10 +0000}, Doi = {10.1016/j.neuron.2012.06.029}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {toread}, Mesh = {Animals; Models, Neurological; Nerve Net; Neural Conduction; Neurons; Visual Cortex}, Month = {Jul}, Number = {2}, Pages = {218-29}, pmid = {22841308}, Pst = {ppublish}, Title = {Traveling waves in visual cortex}, Volume = {75}, Year = {2012}, url = {papers/Sato_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.06.029}} @article{Priebe:2012, Abstract = {Orientation selectivity in the primary visual cortex (V1) is a receptive field property that is at once simple enough to make it amenable to experimental and theoretical approaches and yet complex enough to represent a significant transformation in the representation of the visual image. As a result, V1 has become an area of choice for studying cortical computation and its underlying mechanisms. Here we consider the receptive field properties of the simple cells in cat V1--the cells that receive direct input from thalamic relay cells--and explore how these properties, many of which are highly nonlinear, arise. We have found that many receptive field properties of V1 simple cells fall directly out of Hubel and Wiesel's feedforward model when the model incorporates realistic neuronal and synaptic mechanisms, including threshold, synaptic depression, response variability, and the membrane time constant.}, Author = {Priebe, Nicholas J and Ferster, David}, Date-Added = {2012-11-08 22:31:49 +0000}, Date-Modified = {2012-11-08 22:31:49 +0000}, Doi = {10.1016/j.neuron.2012.06.011}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Animals; Cats; Models, Neurological; Neurons; Synaptic Transmission; Visual Cortex; Visual Pathways}, Month = {Jul}, Number = {2}, Pages = {194-208}, Pmc = {PMC3477598}, pmid = {22841306}, Pst = {ppublish}, Title = {Mechanisms of neuronal computation in mammalian visual cortex}, Volume = {75}, Year = {2012}, url = {papers/Priebe_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.06.011}} @article{Gilbert:2012, Abstract = {The visual cortex has the capacity for experience-dependent change, or cortical plasticity, that is retained throughout life. Plasticity is invoked for encoding information during perceptual learning, by internally representing the regularities of the visual environment, which is useful for facilitating intermediate-level vision--contour integration and surface segmentation. The same mechanisms have adaptive value for functional recovery after CNS damage, such as that associated with stroke or neurodegenerative disease. A common feature to plasticity in primary visual cortex (V1) is an association field that links contour elements across the visual field. The circuitry underlying the association field includes a plexus of long-range horizontal connections formed by cortical pyramidal cells. These connections undergo rapid and exuberant sprouting and pruning in response to removal of sensory input, which can account for the topographic reorganization following retinal lesions. Similar alterations in cortical circuitry may be involved in perceptual learning, and the changes observed in V1 may be representative of how learned information is encoded throughout the cerebral cortex.}, Author = {Gilbert, Charles D and Li, Wu}, Date-Added = {2012-11-08 22:30:32 +0000}, Date-Modified = {2012-11-08 22:30:55 +0000}, Doi = {10.1016/j.neuron.2012.06.030}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {toread}, Mesh = {Animals; Humans; Learning; Neuronal Plasticity; Neurons; Visual Cortex; Visual Perception}, Month = {Jul}, Number = {2}, Pages = {250-64}, Pmc = {PMC3408614}, pmid = {22841310}, Pst = {ppublish}, Title = {Adult visual cortical plasticity}, Volume = {75}, Year = {2012}, url = {papers/Gilbert_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.06.030}} @article{Reid:2012, Abstract = {"Receptive Fields, Binocular Interaction and Functional Architecture in the Cat's Visual Cortex" by Hubel and Wiesel (1962) reported several important discoveries: orientation columns, the distinct structures of simple and complex receptive fields, and binocular integration. But perhaps the paper's greatest influence came from the concept of functional architecture (the complex relationship between in vivo physiology and the spatial arrangement of neurons) and several models of functionally specific connectivity. They thus identified two distinct concepts, topographic specificity and functional specificity, which together with cell-type specificity constitute the major determinants of nonrandom cortical connectivity. Orientation columns are iconic examples of topographic specificity, whereby axons within a column connect with cells of a single orientation preference. Hubel and Wiesel also saw the need for functional specificity at a finer scale in their model of thalamic inputs to simple cells, verified in the 1990s. The difficult but potentially more important question of functional specificity between cortical neurons is only now becoming tractable with new experimental techniques.}, Author = {Reid, R Clay}, Date-Added = {2012-11-08 22:29:53 +0000}, Date-Modified = {2012-11-08 22:31:20 +0000}, Doi = {10.1016/j.neuron.2012.06.031}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {toread}, Mesh = {Animals; Models, Neurological; Nerve Net; Neurons; Orientation; Visual Cortex; Visual Pathways}, Month = {Jul}, Number = {2}, Pages = {209-17}, pmid = {22841307}, Pst = {ppublish}, Title = {From functional architecture to functional connectomics}, Volume = {75}, Year = {2012}, url = {papers/Reid_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.06.031}} @book{finlay:2003, Author = {Finlay, B L}, Date-Added = {2012-11-08 22:04:41 +0000}, Date-Modified = {2012-11-08 22:27:47 +0000}, Editor = {Hopkins}, Keywords = {toread}, Publisher = {Praeger}, Title = {The Developmental Neurobiology of Early Vision}, Year = {2003}, url = {papers/Finlay_2003.pdf}} @article{Roffwarg:1966, Author = {Roffwarg, H P and Muzio, J N and Dement, W C}, Date-Added = {2012-11-08 21:46:57 +0000}, Date-Modified = {2012-11-08 22:03:57 +0000}, Doi = {10.1126/science.152.3722.604}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {toread; human; sleep; oscillations; synchrony; development; Cerebral Cortex; Neocortex; EEG; Fetal Development/physiology}, Month = {Apr}, Number = {3722}, Pages = {604-19}, pmid = {17779492}, Pst = {ppublish}, Title = {Ontogenetic development of the human sleep-dream cycle}, Volume = {152}, Year = {1966}, url = {papers/Roffwarg_Science1966.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.152.3722.604}} @article{Espinosa:2012, Abstract = {Hubel and Wiesel began the modern study of development and plasticity of primary visual cortex (V1), discovering response properties of cortical neurons that distinguished them from their inputs and that were arranged in a functional architecture. Their findings revealed an early innate period of development and a later critical period of dramatic experience-dependent plasticity. Recent studies have used rodents to benefit from biochemistry and genetics. The roles of spontaneous neural activity and molecular signaling in innate, experience-independent development have been clarified, as have the later roles of visual experience. Plasticity produced by monocular visual deprivation (MD) has been dissected into stages governed by distinct signaling mechanisms, some of whose molecular players are known. Many crucial questions remain, but new tools for perturbing cortical cells and measuring plasticity at the level of changes in connections among identified neurons now exist. The future for the study of V1 to illuminate cortical development and plasticity is bright.}, Author = {Espinosa, J Sebastian and Stryker, Michael P}, Date-Added = {2012-11-08 21:03:43 +0000}, Date-Modified = {2013-06-10 19:56:04 +0000}, Doi = {10.1016/j.neuron.2012.06.009}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {topographic map; development; activity-development; review literature; spontaneous activity; experience dependent plasticity; currOpinRvw}, Mesh = {Animals; Neuronal Plasticity; Neurons; Vision, Ocular; Visual Cortex}, Month = {Jul}, Number = {2}, Pages = {230-49}, pmid = {22841309}, Pst = {ppublish}, Title = {Development and plasticity of the primary visual cortex}, Volume = {75}, Year = {2012}, url = {papers/Espinosa_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.06.009}} @article{Takahashi:2011, Abstract = {The immature cortex (cortical plate [CP]) and underlying subplate (SP), a transient cell layer just below the CP, play critical roles in the formation of intracerebral connections. The purpose of this study was to examine the diffusion characteristics of the developing cortex and subcortical structures and compare to histology. We obtained high-resolution diffusion spectrum images of postnatal day (P) 0 (newborn), P35 (pediatric), and P100 (adult) cat brains, performed tractography analysis, and correlated with histological findings. Tractography revealed radial organization and radial afferent/efferent tracts not only in the CP but also in external SP at P0. Radial organization persisted only in the cortex but decreased at P35 and P100. Radial organization correlated with radial cellular organization, with highest cellular density at P0 (Cresyl Violet staining). At P0, the internal SP contained abundant corticocortical and projection tractography pathways, crossing at wide angles in areas with no myelination by Luxol Fast Blue staining. At P35 and P100, increased directional coherence of white matter was observed, with fewer local tracts, but more long association pathways. These results suggest that diffusion tractography can differentially characterize internal and external SP zones and their transition into mature cortical pathways.}, Author = {Takahashi, Emi and Dai, Guangping and Rosen, Glenn D and Wang, Ruopeng and Ohki, Kenichi and Folkerth, Rebecca D and Galaburda, Albert M and Wedeen, Van J and Ellen Grant, P}, Date-Added = {2012-11-08 21:01:24 +0000}, Date-Modified = {2012-11-08 21:01:37 +0000}, Doi = {10.1093/cercor/bhq084}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {toread}, Mesh = {Animals; Animals, Newborn; Axons; Brain Mapping; Cats; Cell Differentiation; Diffusion Tensor Imaging; Image Processing, Computer-Assisted; Neocortex; Neural Pathways}, Month = {Jan}, Number = {1}, Pages = {200-11}, Pmc = {PMC3025725}, pmid = {20494968}, Pst = {ppublish}, Title = {Developing neocortex organization and connectivity in cats revealed by direct correlation of diffusion tractography and histology}, Volume = {21}, Year = {2011}, url = {papers/Takahashi_CerebCortex2011.pdf}} @article{Rubel:2002, Abstract = {The neurons of the cochlear ganglion transmit acoustic information between the inner ear and the brain. These placodally derived neurons must produce a topographically precise pattern of connections in both the inner ear and the brain. In this review, we consider the current state of knowledge concerning the development of these neurons, their peripheral and central connections, and their influences on peripheral and central target cells. Relatively little is known about the cellular and molecular regulation of migration or the establishment of precise topographic connection to the hair cells or cochlear nucleus (CN) neurons. Studies of mice with neurotrophin deletions are beginning to yield increasing understanding of variations in ganglion cell survival and resulting innervation patterns, however. Finally, existing evidence suggests that while ganglion cells have little influence on the differentiation of their hair cell targets, quite the opposite is true in the brain. Ganglion cell innervation and synaptic activity are essential for normal development of neurons in the cochlear nucleus.}, Author = {Rubel, Edwin W and Fritzsch, Bernd}, Date-Added = {2012-11-08 21:00:49 +0000}, Date-Modified = {2012-11-08 21:01:02 +0000}, Doi = {10.1146/annurev.neuro.25.112701.142849}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {Non-programmatic; toread; review literature}, Mesh = {Animals; Auditory Pathways; Cell Communication; Cell Differentiation; Cell Movement; Cochlear Nucleus; Gene Expression Regulation, Developmental; Hair Cells, Auditory; Humans; Nerve Growth Factors; Neurons, Afferent; Spiral Ganglion}, Pages = {51-101}, pmid = {12052904}, Pst = {ppublish}, Title = {Auditory system development: primary auditory neurons and their targets}, Volume = {25}, Year = {2002}, url = {papers/Rubel_AnnuRevNeurosci2002.pdf}} @article{Dunn:2012, Abstract = {Sensory circuits use common strategies, such as convergence and divergence, typically at different synapses, to pool or distribute inputs. Inputs from different presynaptic cell types converge onto a common postsynaptic cell, acting together to shape neuronal output (Klausberger and Somogyi, 2008). Also, individual presynaptic cells contact several postsynaptic cell types, generating divergence of signals. Attaining such complex wiring patterns relies on the orchestration of many events across development, including axonal and dendritic growth and synapse formation and elimination (reviewed by Waites et al., 2005; Sanes and Yamagata, 2009). Recent work has focused on how distinct presynaptic cell types form stereotypic connections with an individual postsynaptic cell (Morgan et al., 2011; Williams et al., 2011), but how a single presynaptic cell type diverges to form distinct wiring patterns with multiple postsynaptic cell types during development remains unexplored. Here we take advantage of the compactness of the visual system's first synapse to observe development of such a circuit in mouse retina. By imaging three types of postsynaptic bipolar cells and their common photoreceptor targets across development, we found that distinct bipolar cell types engage in disparate dendritic growth behaviors, exhibit targeted or exploratory approaches to contact photoreceptors, and adhere differently to the synaptotropic model of establishing synaptic territories. Furthermore each type establishes its final connectivity patterns with the same afferents on separate time scales. We propose that such differences in strategy and timeline could facilitate the division of common inputs among multiple postsynaptic cell types to create parallel circuits with diverse function.}, Author = {Dunn, Felice A and Wong, Rachel O L}, Date-Added = {2012-11-08 20:59:42 +0000}, Date-Modified = {2012-11-08 20:59:53 +0000}, Doi = {10.1523/JNEUROSCI.1581-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread}, Mesh = {Animals; Axons; Dendrites; Mice; Mice, Transgenic; Retina; Retinal Neurons; Synapses; Visual Pathways}, Month = {Jul}, Number = {30}, Pages = {10306-17}, Pmc = {PMC3435432}, pmid = {22836264}, Pst = {ppublish}, Title = {Diverse strategies engaged in establishing stereotypic wiring patterns among neurons sharing a common input at the visual system's first synapse}, Volume = {32}, Year = {2012}, url = {papers/Dunn_JNeurosci2012.pdf}} @article{Rust:2012, Abstract = {Although popular accounts suggest that neurons along the ventral visual processing stream become increasingly selective for particular objects, this appears at odds with the fact that inferior temporal cortical (IT) neurons are broadly tuned. To explore this apparent contradiction, we compared processing in two ventral stream stages (visual cortical areas V4 and IT) in the rhesus macaque monkey. We confirmed that IT neurons are indeed more selective for conjunctions of visual features than V4 neurons and that this increase in feature conjunction selectivity is accompanied by an increase in tolerance ("invariance") to identity-preserving transformations (e.g., shifting, scaling) of those features. We report here that V4 and IT neurons are, on average, tightly matched in their tuning breadth for natural images ("sparseness") and that the average V4 or IT neuron will produce a robust firing rate response (>50% of its peak observed firing rate) to ∼10% of all natural images. We also observed that sparseness was positively correlated with conjunction selectivity and negatively correlated with tolerance within both V4 and IT, consistent with selectivity-building and invariance-building computations that offset one another to produce sparseness. Our results imply that the conjunction-selectivity-building and invariance-building computations necessary to support object recognition are implemented in a balanced manner to maintain sparseness at each stage of processing.}, Author = {Rust, Nicole C and DiCarlo, James J}, Date-Added = {2012-11-08 20:59:08 +0000}, Date-Modified = {2012-11-08 20:59:28 +0000}, Doi = {10.1523/JNEUROSCI.6125-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread}, Mesh = {Animals; Form Perception; Macaca mulatta; Male; Neurons; Pattern Recognition, Visual; Photic Stimulation; Visual Cortex; Visual Pathways}, Month = {Jul}, Number = {30}, Pages = {10170-82}, Pmc = {PMC3485085}, pmid = {22836252}, Pst = {ppublish}, Title = {Balanced increases in selectivity and tolerance produce constant sparseness along the ventral visual stream}, Volume = {32}, Year = {2012}, url = {papers/Rust_JNeurosci2012.pdf}} @article{Cohen-Cory:2002, Abstract = {Synapse formation and stabilization in the vertebrate central nervous system is a dynamic process, requiring bi-directional communication between pre- and postsynaptic partners. Numerous mechanisms coordinate where and when synapses are made in the developing brain. This review discusses cellular and activity-dependent mechanisms that control the development of synaptic connectivity.}, Author = {Cohen-Cory, Susana}, Date-Added = {2012-11-08 20:59:08 +0000}, Date-Modified = {2012-11-12 22:31:37 +0000}, Doi = {10.1126/science.1075510}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {toread; Structure-Activity Relationship; development; synapse formation; synapses; Synaptic Transmission; axon guidance; activity manipulation; Spontaneous activity; review literature}, Mesh = {Animals; Axons; Brain; Cells, Cultured; Dendrites; Nerve Growth Factors; Neuromuscular Junction; Neuronal Plasticity; Neurons; Neurotransmitter Agents; Receptors, Neurotransmitter; Synapses; Synaptic Transmission; Synaptic Vesicles; Visual Cortex; Visual Pathways}, Month = {Oct}, Number = {5594}, Pages = {770-6}, pmid = {12399577}, Pst = {ppublish}, Title = {The developing synapse: construction and modulation of synaptic structures and circuits}, Volume = {298}, Year = {2002}, url = {papers/Cohen-Cory_Science2002.pdf}} @article{Economides:2012, Abstract = {Misalignment of the eyes can lead to double vision and visual confusion. However, these sensations are rare when strabismus is acquired early in life, because the extra image is suppressed. To explore the mechanism of perceptual suppression in strabismus, the visual fields were mapped binocularly in 14 human subjects with exotropia. Subjects wore red/blue filter glasses to permit dichoptic stimulation while fixating a central target on a tangent screen. A purple stimulus was flashed at a peripheral location; its reported color ("red" or "blue") revealed which eye's image was perceived at that locus. The maps showed a vertical border between the center of gaze for each eye, splitting the visual field into two separate regions. In each region, perception was mediated by only one eye, with suppression of the other eye. Unexpectedly, stimuli falling on the fovea of the deviated eye were seen in all subjects. However, they were perceived in a location shifted by the angle of ocular deviation. This plasticity in the coding of visual direction allows accurate localization of objects everywhere in the visual scene, despite the presence of strabismus.}, Author = {Economides, John R and Adams, Daniel L and Horton, Jonathan C}, Date-Added = {2012-11-08 20:57:25 +0000}, Date-Modified = {2012-11-08 20:57:56 +0000}, Doi = {10.1523/JNEUROSCI.1435-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread}, Mesh = {Adolescent; Adult; Child; Exotropia; Female; Fixation, Ocular; Humans; Male; Middle Aged; Photic Stimulation; Vision, Binocular; Visual Fields; Visual Perception}, Month = {Jul}, Number = {30}, Pages = {10286-95}, Pmc = {PMC3435149}, pmid = {22836262}, Pst = {ppublish}, Title = {Perception via the deviated eye in strabismus}, Volume = {32}, Year = {2012}, url = {papers/Economides_JNeurosci2012.pdf}} @article{Liang:2012, Abstract = {The neural mechanism of unconsciousness has been a major unsolved question in neuroscience despite its vital role in brain states like coma and anesthesia. The existing literature suggests that neural connections, information integration, and conscious states are closely related. Indeed, alterations in several important neural circuitries and networks during unconscious conditions have been reported. However, how the whole-brain network is topologically reorganized to support different patterns of information transfer during unconscious states remains unknown. Here we directly compared whole-brain neural networks in awake and anesthetized states in rodents. Consistent with our previous report, the awake rat brain was organized in a nontrivial manner and conserved fundamental topological properties in a way similar to the human brain. Strikingly, these topological features were well maintained in the anesthetized brain. Local neural networks in the anesthetized brain were reorganized with altered local network properties. The connectional strength between brain regions was also considerably different between the awake and anesthetized conditions. Interestingly, we found that long-distance connections were not preferentially reduced in the anesthetized condition, arguing against the hypothesis that loss of long-distance connections is characteristic to unconsciousness. These findings collectively show that the integrity of the whole-brain network can be conserved between widely dissimilar physiologic states while local neural networks can flexibly adapt to new conditions. They also illustrate that the governing principles of intrinsic brain organization might represent fundamental characteristics of the healthy brain. With the unique spatial and temporal scales of resting-state fMRI, this study has opened a new avenue for understanding the neural mechanism of (un)consciousness.}, Author = {Liang, Zhifeng and King, Jean and Zhang, Nanyin}, Date-Added = {2012-11-08 20:57:25 +0000}, Date-Modified = {2013-09-26 17:19:03 +0000}, Doi = {10.1523/JNEUROSCI.1020-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {default mode network; fmri; rat; in vivo; connectivity; wholeBrain; spontaneous activity}, Mesh = {Anesthesia; Anesthetics, Inhalation; Animals; Brain; Brain Mapping; Consciousness; Image Processing, Computer-Assisted; Isoflurane; Magnetic Resonance Imaging; Male; Nerve Net; Neuroimaging; Rats; Rats, Long-Evans}, Month = {Jul}, Number = {30}, Pages = {10183-91}, Pmc = {PMC3422560}, pmid = {22836253}, Pst = {ppublish}, Title = {Intrinsic organization of the anesthetized brain}, Volume = {32}, Year = {2012}, url = {papers/Liang_JNeurosci2012.pdf}} @article{Mao:2012, Abstract = {Brain damage resulting in loss of sensory stimulation can induce reorganization of sensory maps in cerebral cortex. Previous research on recovery from brain damage has focused primarily on adaptive plasticity within the affected modality. Less attention has been paid to maladaptive plasticity that may arise as a result of ectopic innervation from other modalities. Using ferrets in which neonatal midbrain damage results in diversion of retinal projections to the auditory thalamus, we investigated how auditory cortical function is impacted by the resulting ectopic visual activation. We found that, although auditory neurons in cross-modal auditory cortex (XMAC) retained sound frequency tuning, their thresholds were increased, their tuning was broader, and tonotopic order in their frequency maps was disturbed. Multisensory neurons in XMAC also exhibited frequency tuning, but they had longer latencies than normal auditory neurons, suggesting they arise from multisynaptic, non-geniculocortical sources. In a control group of animals with neonatal deafferentation of auditory thalamus but without redirection of retinal axons, tonotopic order and sharp tuning curves were seen, indicating that this aspect of auditory function had developed normally. This result shows that the compromised auditory function in XMAC results from invasion by ectopic visual inputs and not from deafferentation. These findings suggest that the cross-modal plasticity that commonly occurs after loss of sensory input can significantly interfere with recovery from brain damage and that mitigation of maladaptive effects is critical to maximizing the potential for recovery.}, Author = {Mao, Yu-Ting and Pallas, Sarah L}, Date-Added = {2012-11-08 20:57:25 +0000}, Date-Modified = {2012-11-08 20:57:56 +0000}, Doi = {10.1523/JNEUROSCI.6524-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread}, Mesh = {Acoustic Stimulation; Animals; Auditory Cortex; Auditory Pathways; Axons; Female; Ferrets; Male; Neuronal Plasticity; Neurons; Thalamus; Visual Pathways}, Month = {Jul}, Number = {30}, Pages = {10338-51}, Pmc = {PMC3428959}, pmid = {22836267}, Pst = {ppublish}, Title = {Compromise of auditory cortical tuning and topography after cross-modal invasion by visual inputs}, Volume = {32}, Year = {2012}, url = {papers/Mao_JNeurosci2012.pdf}} @article{Emsley:2004, Abstract = {During the past three decades, research exploring potential neuronal replacement therapies has focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. However, in the last decade, the development of novel approaches has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain, and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent advances in our understanding of related events of neural development and plasticity, including the role of radial glia in developmental neurogenesis, and the ability of endogenous precursors present in the adult brain to be induced to produce neurons and partially repopulate brain regions affected by neurodegenerative processes, have led to fundamental changes in the views about how the brain develops, as well as to approaches by which transplanted or endogenous precursors might be used to repair the adult brain. For example, recruitment of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and, in some cases, newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow for the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that might not require transplantation of exogenous cells.}, Author = {Emsley, Jason G and Mitchell, Bartley D and Magavi, Sanjay S P and Arlotta, Paola and Macklis, Jeffrey D}, Date-Added = {2012-11-08 17:31:10 +0000}, Date-Modified = {2012-11-08 17:31:40 +0000}, Doi = {10.1602/neurorx.1.4.452}, Journal = {NeuroRx}, Journal-Full = {NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics}, Keywords = {Adult Neurogenesis; transplant regeneration}, Mesh = {Animals; Cell Death; Cell Differentiation; Cell Movement; Cerebral Cortex; Humans; Nerve Net; Nerve Regeneration; Nerve Tissue; Nervous System Diseases; Signal Transduction; Stem Cell Transplantation}, Month = {Oct}, Number = {4}, Pages = {452-71}, Pmc = {PMC534952}, pmid = {15717047}, Pst = {ppublish}, Title = {The repair of complex neuronal circuitry by transplanted and endogenous precursors}, Volume = {1}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1602/neurorx.1.4.452}} @article{Maravall:2004, Abstract = {In rat barrel cortex, development of layer 2/3 receptive fields can be disrupted by sensory deprivation, with a critical period ending around postnatal day (PND) 14. To determine if experience-dependent plasticity of dendritic morphology could contribute to the reorganization of synaptic inputs, we analyzed dendritic structure in acute brain slices using two-photon laser scanning microscopy (2PLSM) and automated segmentation and analysis software. Layer 2/3 pyramidal cells from control and deprived rats were imaged from PND 9 to PND 20, spanning the critical period. Detailed analyses were performed on basal arbors, which receive the majority of synaptic input from layer 4. Some parameters (number of primary dendrites, volume subtended, aspect ratios) were stable, suggesting that development of several important properties of basal arbors has ceased by age PND 9. However, the spatial organization of secondary branching changed with age and experience. In older neurons there was a larger fraction of branch points farther from the soma. Deprivation from age PND 9 delayed these changes in secondary branching. This effect of deprivation was rapid (detectable at PND 10) and present at all ages observed. Deprivation initiated at PND 15 had no effect on basal branching measured at PND 20. Thus the spatial organization of secondary dendritic branching is experience-dependent and shares a critical period with receptive field plasticity.}, Author = {Maravall, Miguel and Koh, Ingrid Y Y and Lindquist, W Brent and Svoboda, Karel}, Date-Added = {2012-11-08 17:25:56 +0000}, Date-Modified = {2012-11-08 17:28:21 +0000}, Doi = {10.1093/cercor/bhh026}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {21 Activity-development; development; barrels; Somatosensory Cortex; rat; rodent; spines; Dendrites; structural remodeling; Structure-Activity Relationship; in vitro; multiphoton; Sensory Deprivation}, Mesh = {Adaptation, Physiological; Aging; Animals; Animals, Newborn; Dendrites; Neocortex; Nerve Net; Neuronal Plasticity; Pyramidal Cells; Rats; Sensory Deprivation}, Month = {Jun}, Number = {6}, Pages = {655-64}, pmid = {15054062}, Pst = {ppublish}, Title = {Experience-dependent changes in basal dendritic branching of layer 2/3 pyramidal neurons during a critical period for developmental plasticity in rat barrel cortex}, Volume = {14}, Year = {2004}, url = {papers/Maravall_CerebCortex2004.pdf}} @article{Parvizi:2012, Abstract = {Face-selective neural responses in the human fusiform gyrus have been widely examined. However, their causal role in human face perception is largely unknown. Here, we used a multimodal approach of electrocorticography (ECoG), high-resolution functional magnetic resonance imaging (fMRI), and electrical brain stimulation (EBS) to directly investigate the causal role of face-selective neural responses of the fusiform gyrus (FG) in face perception in a patient implanted with subdural electrodes in the right inferior temporal lobe. High-resolution fMRI identified two distinct FG face-selective regions [mFus-faces and pFus-faces (mid and posterior fusiform, respectively)]. ECoG revealed a striking anatomical and functional correspondence with fMRI data where a pair of face-selective electrodes, positioned 1 cm apart, overlapped mFus-faces and pFus-faces, respectively. Moreover, electrical charge delivered to this pair of electrodes induced a profound face-specific perceptual distortion during viewing of real faces. Specifically, the subject reported a "metamorphosed" appearance of faces of people in the room. Several controls illustrate the specificity of the effect to the perception of faces. EBS of mFus-faces and pFus-faces neither produced a significant deficit in naming pictures of famous faces on the computer, nor did it affect the appearance of nonface objects. Further, the appearance of faces remained unaffected during both sham stimulation and stimulation of a pair of nearby electrodes that were not face-selective. Overall, our findings reveal a striking convergence of fMRI, ECoG, and EBS, which together offer a rare causal link between functional subsets of the human FG network and face perception.}, Author = {Parvizi, Josef and Jacques, Corentin and Foster, Brett L and Withoft, Nathan and Rangarajan, Vinitha and Weiner, Kevin S and Grill-Spector, Kalanit}, Date-Added = {2012-11-05 19:30:59 +0000}, Date-Modified = {2012-11-05 19:32:16 +0000}, Doi = {10.1523/JNEUROSCI.2609-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {visual system; function; fmri; human; epilepsy; seizure; visual map; Perception; Face; Neurophysiology; extracellular; eeg; toread}, Month = {Oct}, Number = {43}, Pages = {14915-20}, pmid = {23100414}, Pst = {ppublish}, Title = {Electrical stimulation of human fusiform face-selective regions distorts face perception}, Volume = {32}, Year = {2012}, url = {papers/Parvizi_JNeurosci2012.pdf}, Bdsk-Url-1 = {http://news.sciencemag.org/sciencenow/2012/10/identifying-the-brains-own-facia.html?ref=em}} @article{Narboux-Neme:2012, Abstract = {To assess the impact of synaptic neurotransmitter release on neural circuit development, we analyzed barrel cortex formation after thalamic or cortical ablation of RIM1 and RIM2 proteins, which control synaptic vesicle fusion. Thalamus-specific deletion of RIMs reduced neurotransmission efficacy by 67%. A barrelless phenotype was found with a dissociation of effects on the presynaptic and postsynaptic cellular elements of the barrel. Presynaptically, thalamocortical axons formed a normal whisker map, whereas postsynaptically the cytoarchitecture of layer IV neurons was altered as spiny stellate neurons were evenly distributed and their dendritic trees were symmetric. Strikingly, cortex-specific deletion of the RIM genes did not modify barrel development. Adult mice with thalamic-specific RIM deletion showed a lack of activity-triggered immediate early gene expression and altered sensory-related behaviors. Thus, efficient synaptic release is required at thalamocortical but not at corticocortical synapses for building the whisker to barrel map and for efficient sensory function.}, Author = {Narboux-N{\^e}me, Nicolas and Evrard, Alexis and Ferezou, Isabelle and Erzurumlu, Reha S and Kaeser, Pascal S and Lain{\'e}, Jeanne and Rossier, Jean and Ropert, Nicole and S{\"u}dhof, Thomas C and Gaspar, Patricia}, Date-Added = {2012-11-05 18:10:09 +0000}, Date-Modified = {2012-11-05 18:11:39 +0000}, Doi = {10.1523/JNEUROSCI.0343-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread; barrels; Somatosensory Cortex; Neocortex; Cerebral Cortex; mouse; Structure-Activity Relationship; activity manipulation; synapse formation; topographic map; sensory map; Sensory Deprivation; transgenic}, Mesh = {Animals; Axons; Cerebral Cortex; Female; Male; Mice; Neuronal Plasticity; Neurotransmitter Agents; Somatosensory Cortex; Synapses; Synaptic Transmission; Thalamus; Touch; Vibrissae}, Month = {May}, Number = {18}, Pages = {6183-96}, pmid = {22553025}, Pst = {ppublish}, Title = {Neurotransmitter release at the thalamocortical synapse instructs barrel formation but not axon patterning in the somatosensory cortex}, Volume = {32}, Year = {2012}, url = {papers/Narboux-Nême_JNeurosci2012.pdf}} @article{Barkovich:2012, Abstract = {Malformations of the midbrain (MB) and hindbrain (HB) have become topics of considerable interest in the neurology and neuroscience literature in recent years. The combined advances of imaging and molecular biology have improved analyses of structures in these areas of the central nervous system, while advances in genetics have made it clear that malformations of these structures are often associated with dysfunction or malformation of other organ systems. This review focuses upon the importance of communication between clinical researchers and basic scientists in the advancement of knowledge of this group of disorders. Disorders of anteroposterior (AP) patterning, cerebellar hypoplasias, disorders associated with defects of the pial limiting membrane (cobblestone cortex), disorders of the Reelin pathway, and disorders of the primary cilium/basal body organelle (molar tooth malformations) are the main focus of the review.}, Author = {Barkovich, A James}, Date-Added = {2012-11-05 18:08:25 +0000}, Date-Modified = {2012-11-05 18:09:30 +0000}, Doi = {10.3389/fnana.2012.00007}, Journal = {Front Neuroanat}, Journal-Full = {Frontiers in neuroanatomy}, Keywords = {cortical malformation; development; neurological disorder; Cerebellar Cortex; Cerebellum; optic tectum; midbrain; Superior Colliculus; fmri; human; review; toread; grants; ideas}, Month = {Jan}, Pages = {7}, Pmc = {PMC3294267}, pmid = {22408608}, Pst = {ppublish}, Title = {Developmental disorders of the midbrain and hindbrain}, Volume = {6}, Year = {2012}, url = {papers/Barkovich_FrontNeuroanat2012.pdf}} @article{Wang:2012, Abstract = {Much of the information used for visual perception and visually guided actions is processed in complex networks of connections within the cortex. To understand how this works in the normal brain and to determine the impact of disease, mice are promising models. In primate visual cortex, information is processed in a dorsal stream specialized for visuospatial processing and guided action and a ventral stream for object recognition. Here, we traced the outputs of 10 visual areas and used quantitative graph analytic tools of modern network science to determine, from the projection strengths in 39 cortical targets, the community structure of the network. We found a high density of the cortical graph that exceeded that shown previously in monkey. Each source area showed a unique distribution of projection weights across its targets (i.e., connectivity profile) that was well fit by a lognormal function. Importantly, the community structure was strongly dependent on the location of the source area: outputs from medial/anterior extrastriate areas were more strongly linked to parietal, motor, and limbic cortices, whereas lateral extrastriate areas were preferentially connected to temporal and parahippocampal cortices. These two subnetworks resemble dorsal and ventral cortical streams in primates, demonstrating that the basic layout of cortical networks is conserved across species.}, Author = {Wang, Quanxin and Sporns, Olaf and Burkhalter, Andreas}, Date-Added = {2012-11-05 18:05:37 +0000}, Date-Modified = {2012-11-05 18:07:54 +0000}, Doi = {10.1523/JNEUROSCI.6063-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {connectivity; connectome; mouse; Cerebral Cortex; Neocortex; visual system; network; Anatomy; Histological Techniques; Structure-Activity Relationship; graph theory; toread; callosal; visual cortex; Association cortex; function}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Female; Iontophoresis; Male; Mice; Mice, Inbred C57BL; Models, Statistical; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Neuronal Tract-Tracers; Visual Cortex}, Month = {Mar}, Number = {13}, Pages = {4386-99}, Pmc = {PMC3328193}, pmid = {22457489}, Pst = {ppublish}, Title = {Network analysis of corticocortical connections reveals ventral and dorsal processing streams in mouse visual cortex}, Volume = {32}, Year = {2012}, url = {papers/Wang_JNeurosci2012.pdf}} @article{Nicol:2007, Abstract = {Spontaneous activity generated in the retina is necessary to establish a precise retinotopic map, but the underlying mechanisms are poorly understood. We demonstrate here that neural activity controls ephrin-A-mediated responses. In the mouse retinotectal system, we show that spontaneous activity of the retinal ganglion cells (RGCs) is needed, independently of synaptic transmission, for the ordering of the retinotopic map and the elimination of exuberant retinal axons. Activity blockade suppressed the repellent action of ephrin-A on RGC growth cones by cyclic AMP (cAMP)-dependent pathways. Unexpectedly, the ephrin-A5-induced retraction required cAMP oscillations rather than sustained increases in intracellular cAMP concentrations. Periodic photo-induced release of caged cAMP in growth cones rescued the response to ephrin-A5 when activity was blocked. These results provide a direct molecular link between spontaneous neural activity and axon guidance mechanisms during the refinement of neural maps.}, Author = {Nicol, Xavier and Voyatzis, Sylvie and Muzerelle, Aude and Narboux-N{\^e}me, Nicolas and S{\"u}dhof, Thomas C and Miles, Richard and Gaspar, Patricia}, Date-Added = {2012-11-05 18:01:02 +0000}, Date-Modified = {2012-11-05 18:03:52 +0000}, Doi = {10.1038/nn1842}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Calcium Signaling; Calcium Channels; oscillations; Spontaneous activity; retinal waves; Retinal Ganglion Cells; Ephrins; mouse; Superior Colliculus; optic tectum; retinotopy; topographic map; visual system; development; axon guidance; Structure-Activity Relationship; synapse formation; grants; ideas}, Mesh = {1-Methyl-3-isobutylxanthine; Action Potentials; Animals; Cyclic AMP; Embryo, Mammalian; Ephrin-A5; Excitatory Amino Acid Antagonists; Growth Cones; Mice; Mice, Knockout; Munc18 Proteins; Organ Culture Techniques; Periodicity; Phosphodiesterase Inhibitors; Quinoxalines; Retina; Retinal Ganglion Cells; Signal Transduction; Tetrodotoxin; Visual Pathways}, Month = {Mar}, Number = {3}, Pages = {340-7}, pmid = {17259982}, Pst = {ppublish}, Title = {cAMP oscillations and retinal activity are permissive for ephrin signaling during the establishment of the retinotopic map}, Volume = {10}, Year = {2007}, url = {papers/Nicol_NatNeurosci2007.pdf}} @article{Mukamel:2010, Abstract = {Direct recordings in monkeys have demonstrated that neurons in frontal and parietal areas discharge during execution and perception of actions [1-8]. Because these discharges "reflect" the perceptual aspects of actions of others onto the motor repertoire of the perceiver, these cells have been called mirror neurons. Their overlapping sensory-motor representations have been implicated in observational learning and imitation, two important forms of learning [9]. In humans, indirect measures of neural activity support the existence of sensory-motor mirroring mechanisms in homolog frontal and parietal areas [10, 11], other motor regions [12-15], and also the existence of multisensory mirroring mechanisms in nonmotor regions [16-19]. We recorded extracellular activity from 1177 cells in human medial frontal and temporal cortices while patients executed or observed hand grasping actions and facial emotional expressions. A significant proportion of neurons in supplementary motor area, and hippocampus and environs, responded to both observation and execution of these actions. A subset of these neurons demonstrated excitation during action-execution and inhibition during action-observation. These findings suggest that multiple systems in humans may be endowed with neural mechanisms of mirroring for both the integration and differentiation of perceptual and motor aspects of actions performed by self and others.}, Author = {Mukamel, Roy and Ekstrom, Arne D and Kaplan, Jonas and Iacoboni, Marco and Fried, Itzhak}, Date-Added = {2012-11-05 17:52:36 +0000}, Date-Modified = {2012-11-05 17:55:30 +0000}, Doi = {10.1016/j.cub.2010.02.045}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {sensory-motor; function; mirror neuron; mirror symmetry; Perception; human; Neurophysiology; extracellular; Frontal Lobe; Temporal Lobe; multimodal}, Mesh = {Animals; Cerebral Cortex; Electrophysiology; Emotions; Facial Expression; Hand; Humans; Imitative Behavior; Motor Activity; Neurons; Psychomotor Performance; Visual Perception}, Month = {Apr}, Number = {8}, Pages = {750-6}, Pmc = {PMC2904852}, pmid = {20381353}, Pst = {ppublish}, Title = {Single-neuron responses in humans during execution and observation of actions}, Volume = {20}, Year = {2010}, url = {papers/Mukamel_CurrBiol2010.pdf}} @article{Mane:2012, Abstract = {Spreading depression (SD) is characterized by a sustained near-complete depolarization of neurons, a massive depolarization of glia, and a negative deflection of the extracellular DC potential. These electrophysiological signs are accompanied by an intrinsic optical signal (IOS) which arises from changes in light scattering and absorption. Even though the underlying mechanisms are unclear, the IOS serves as non-invasive tool to define the spatiotemporal dynamics of SD in brain slices. Usually the tissue is illuminated by white light, and light reflectance or transmittance is monitored. Using a polychromatic, fast-switchable light source we now performed temporo-spectral recordings of the IOS associated with hypoxia-induced SD-like depolarization (HSD) in rat hippocampal slices kept in an interface recording chamber. Recording full illumination spectra (320-680 nm) yielded distinct reflectance profiles for the different phases of HSD. Early during hypoxia tissue reflectance decreased within almost the entire spectrum due to cell swelling. HSD was accompanied by a reversible reflectance increase being most pronounced at 400 nm and 460 nm. At 440 nm massive porphyrin absorption (Soret band) was detected. Hypotonic solutions, Ca(2+)-withdrawal and glial poisoning intensified the reflectance increase during HSD, whereas hypertonic solutions dampened it. Replacement of Cl(-) inverted the reflectance increase. Inducing HSD by cyanide distorted the IOS and reflectance at 340-400 nm increased irreversibly. The pronounced changes at short wavelengths (380 nm, 460 nm) and their cyanide sensitivity suggest that block of mitochondrial metabolism contributes to the IOS during HSD. For stable and reliable IOS recordings during HSD wavelengths of 460-560 nm are recommended.}, Author = {Man{\'e}, Maria and M{\"u}ller, Michael}, Date-Added = {2012-11-05 17:52:36 +0000}, Date-Modified = {2012-11-05 17:57:10 +0000}, Doi = {10.1371/journal.pone.0043981}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {Hypoxia-Ischemia; hypoxic; oscillations; synchrony; Spontaneous activity; Neuron-Glia/*physiology; Neurophysiology; optical imaging; optical physiology; intrinsic signal; glia; excitotoxcity}, Number = {8}, Pages = {e43981}, Pmc = {PMC3430631}, pmid = {22952835}, Pst = {ppublish}, Title = {Temporo-spectral imaging of intrinsic optical signals during hypoxia-induced spreading depression-like depolarization}, Volume = {7}, Year = {2012}, url = {papers/Mané_PLoSOne2012.pdf}} @article{Lin:2012, Abstract = {Amblyopia, also known as lazy eye, usually occurs during early childhood and results in poor or blurred vision. Recent neuroimaging studies have found cortical structural/functional abnormalities in amblyopia. However, until now, it was still not known whether the spontaneous activity of the brain changes in amblyopia subjects. In the present study, regional homogeneity (ReHo), a measure of the homogeneity of functional magnetic resonance imaging signals, was used for the first time to investigate changes in resting-state local spontaneous brain activity in individuals with anisometropic amblyopia. Compared with age- and gender-matched subjects with normal vision, the anisometropic amblyopia subjects showed decreased ReHo of spontaneous brain activity in the right precuneus, the left medial prefrontal cortex, the left inferior frontal gyrus, and the left cerebellum, and increased ReHo of spontaneous brain activity was found in the bilateral conjunction area of the postcentral and precentral gyri, the left paracentral lobule, the left superior temporal gyrus, the left fusiform gyrus, the conjunction area of the right insula, putamen and the right middle occipital gyrus. The observed decreases in ReHo may reflect decreased visuo-motor processing ability, and the increases in ReHo in the somatosensory cortices, the motor areas and the auditory area may indicate compensatory plasticity in amblyopia.}, Author = {Lin, Xiaoming and Ding, Kun and Liu, Yong and Yan, Xiaohe and Song, Shaojie and Jiang, Tianzi}, Date-Added = {2012-11-05 17:52:36 +0000}, Date-Modified = {2012-11-05 17:59:33 +0000}, Doi = {10.1371/journal.pone.0043373}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {resting state; default mode network; amblyopia; Spontaneous activity; function; connectivity; fMRI; human; Cerebral Cortex; visual system; sensory-motor; activity manipulation; Sensory Deprivation; plasticity; toread; ideas; grants}, Number = {8}, Pages = {e43373}, Pmc = {PMC3427333}, pmid = {22937041}, Pst = {ppublish}, Title = {Altered spontaneous activity in anisometropic amblyopia subjects: revealed by resting-state FMRI}, Volume = {7}, Year = {2012}, url = {papers/Lin_PLoSOne2012.pdf}} @article{Grinevich:2005, Abstract = {The mammalian motor cortex typically innervates motor neurons indirectly via oligosynaptic pathways. However, evolution of skilled digit movements in humans, apes, and some monkey species is associated with the emergence of abundant monosynaptic cortical projections onto spinal motor neurons innervating distal limb muscles. Rats perform skilled movements with their whiskers, and we examined the possibility that the rat vibrissa motor cortex (VMC) projects monosynaptically onto facial motor neurons controlling the whisker movements. First, single injections of lentiviruses to VMC sites identified by intracortical microstimulations were used to label a distinct subpopulation of VMC axons or presynaptic terminals by expression of enhanced green fluorescent protein (GFP) or GFP-tagged synaptophysin, respectively. Four weeks after the injections, GFP and synaptophysin-GFP labeling of axons and putative presynaptic terminals was detected in the lateral portion of the facial nucleus (FN), in close proximity to motor neurons identified morphologically and by axonal back-labeling from the whisker follicles. The VMC projections were detected bilaterally, with threefold larger density of labeling in the contralateral FN. Next, multiple VMC injections were used to label a large portion of VMC axons, resulting in overall denser but still laterally restricted FN labeling. Ultrastructural analysis of the GFP-labeled VMC axons confirmed the existence of synaptic contacts onto dendrites and somata of FN motor neurons. These findings provide anatomical demonstration of monosynaptic VMC-to-FN pathway in the rat and show that lentivirus-based expression of GFP and GFP-tagged presynaptic proteins can be used as a high-resolution neuroanatomical tracing method.}, Author = {Grinevich, Valery and Brecht, Michael and Osten, Pavel}, Date-Added = {2012-11-05 17:48:40 +0000}, Date-Modified = {2012-11-05 17:52:11 +0000}, Doi = {10.1523/JNEUROSCI.2235-05.2005}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {18 Classic Neuroanatomy Physiology;16 Barrels;Technique; Cerebral Cortex; Neocortex; topographic map; sensory-motor; sensory map; Somatosensory Cortex}, Mesh = {Animals; Axons; Electric Stimulation; Face; Genes, Reporter; Green Fluorescent Proteins; Lentivirus; Motor Cortex; Motor Neurons; Movement; Pyramidal Cells; Rats; Synapses; Vibrissae}, Month = {Sep}, Number = {36}, Pages = {8250-8}, pmid = {16148232}, Pst = {ppublish}, Title = {Monosynaptic pathway from rat vibrissa motor cortex to facial motor neurons revealed by lentivirus-based axonal tracing}, Volume = {25}, Year = {2005}, url = {papers/Grinevich_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2235-05.2005}} @article{Komai:2006a, Abstract = {Sensory experience is necessary for normal cortical development. This has been shown by sensory deprivation and pharmacological perturbation of the cortex. Because these manipulations affect the cortical network as a whole, the role of postsynaptic cellular properties during experience-dependent development is unclear. Here we addressed the developmental role of somatodendritic excitability, which enables postsynaptic spike timing-dependent forms of plasticity, in rat somatosensory cortex. We used short interfering RNA (siRNA)-based knockdown of Na+ channels to suppress the somatodendritic excitability of small numbers of layer 2/3 pyramidal neurons in the barrel cortex, without altering the ascending sensory pathway. In vivo recordings from siRNA-expressing cells revealed that this manipulation interfered with the normal developmental strengthening of sensory responses. The sensory responsiveness of neighboring cortical neurons was unchanged, indicating that the cortical network was unchanged. We conclude that somatodendritic excitability of the postsynaptic neuron is needed for the regulation of synaptic strength in the developing sensory cortex.}, Author = {Komai, Shoji and Licznerski, Pawel and Cetin, Ali and Waters, Jack and Denk, Winfried and Brecht, Michael and Osten, Pavel}, Date-Added = {2012-11-05 17:48:40 +0000}, Date-Modified = {2012-11-05 17:48:40 +0000}, Doi = {10.1038/nn1752}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Mesh = {Animals; DNA, Recombinant; Excitatory Postsynaptic Potentials; Green Fluorescent Proteins; Lentivirus; Microscopy, Confocal; Neuronal Plasticity; Pyramidal Cells; RNA Interference; RNA, Small Interfering; Rats; Rats, Wistar; Sensory Deprivation; Sodium Channels; Somatosensory Cortex; Synaptic Transmission}, Month = {Sep}, Number = {9}, Pages = {1125-33}, pmid = {16921372}, Pst = {ppublish}, Title = {Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development}, Volume = {9}, Year = {2006}, url = {papers/Komai_NatNeurosci2006.pdf}} @article{Baudouin:2012, Abstract = {The genetic heterogeneity of autism poses a major challenge for identifying mechanism-based treatments. A number of rare mutations are associated with autism, and it is unclear whether these result in common neuronal alterations. Monogenic syndromes, such as fragile X, include autism as one of their multifaceted symptoms and have revealed specific defects in synaptic plasticity. We discovered an unexpected convergence of synaptic pathophysiology in a nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3 knockout mice (a model for nonsyndromic autism) exhibited disrupted heterosynaptic competition and perturbed metabotropic glutamate receptor-dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be rescued by reexpression of neuroligin-3 in juvenile mice, highlighting the possibility of reverting neuronal circuit alterations in autism after the completion of development.}, Author = {Baudouin, St{\'e}phane J and Gaudias, Julien and Gerharz, Stefan and Hatstatt, Laetitia and Zhou, Kuikui and Punnakkal, Pradeep and Tanaka, Kenji F and Spooren, Will and Hen, Rene and De Zeeuw, Chris I and Vogt, Kaspar and Scheiffele, Peter}, Date-Added = {2012-11-05 17:44:14 +0000}, Date-Modified = {2012-11-05 17:46:47 +0000}, Doi = {10.1126/science.1224159}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {autism; Autistic Disorder; function; Synaptic Transmission; Neurophysiology; Electrophysiology; Patch-Clamp Techniques; mouse; transgenic; Transgenes; Behavior; connectivity; toread}, Mesh = {Animals; Autistic Disorder; Cell Adhesion Molecules, Neuronal; Disease Models, Animal; Fragile X Syndrome; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Net; Nerve Tissue Proteins; Neuronal Plasticity; Synapses}, Month = {Oct}, Number = {6103}, Pages = {128-32}, pmid = {22983708}, Pst = {ppublish}, Title = {Shared synaptic pathophysiology in syndromic and nonsyndromic rodent models of autism}, Volume = {338}, Year = {2012}, url = {papers/Baudouin_Science2012.pdf}} @article{Ragan:2012, Abstract = {Here we describe an automated method, named serial two-photon (STP) tomography, that achieves high-throughput fluorescence imaging of mouse brains by integrating two-photon microscopy and tissue sectioning. STP tomography generates high-resolution datasets that are free of distortions and can be readily warped in three dimensions, for example, for comparing multiple anatomical tracings. This method opens the door to routine systematic studies of neuroanatomy in mouse models of human brain disorders.}, Author = {Ragan, Timothy and Kadiri, Lolahon R and Venkataraju, Kannan Umadevi and Bahlmann, Karsten and Sutin, Jason and Taranda, Julian and Arganda-Carreras, Ignacio and Kim, Yongsoo and Seung, H Sebastian and Osten, Pavel}, Date-Added = {2012-11-05 17:44:14 +0000}, Date-Modified = {2012-11-05 17:48:05 +0000}, Doi = {10.1038/nmeth.1854}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {Methods; Technique; multiphoton; mouse; Anatomy; connectivity; histology; Histological Techniques; microscopy; toread}, Mesh = {Anatomy, Cross-Sectional; Animals; Brain; Image Interpretation, Computer-Assisted; Mice; Mice, Transgenic; Microscopy, Fluorescence, Multiphoton; Pattern Recognition, Automated; Tomography}, Month = {Mar}, Number = {3}, Pages = {255-8}, Pmc = {PMC3297424}, pmid = {22245809}, Pst = {epublish}, Title = {Serial two-photon tomography for automated ex vivo mouse brain imaging}, Volume = {9}, Year = {2012}, url = {papers/Ragan_NatMethods2012.pdf}} @article{Yang:2012, Abstract = {The basic circuitry of auditory, visual, somatosensory and other cortical areas is highly stereotyped (Douglas and Martin, 2004). However, it remains unclear whether this anatomical stereotypy implies functional homogeneity, or whether instead different cortical areas are specialized to process the diverse sensory inputs they receive. Here we have used a two alternative forced choice task to assess modality-specific differences in the ability of rats to exploit precise neuronal timing. We delivered pairs of electrical pulses directly to different areas of cortex to determine the minimum timing differences subjects could detect. By stimulating the cortex directly, we isolated differences due to cortical circuitry rather than to sensory transduction and subcortical processing. Surprisingly, the minimum detectable timing differences varied over more than an order of magnitude, ranging from 1 ms in barrel cortex to 15 ms in visual cortex. Furthermore, these modality-specific differences depended upon sensory experience: although animals subjected to whisker clipping initially showed an impaired ability to exploit fine timing in barrel cortical stimulation, behavioral training partially rescued this deficit. Our results suggest that different cortical areas are adapted to the specific structure of the input signals they process, and that precise spike timing may play a more important role for some cortical areas than for others.}, Author = {Yang, Yang and Zador, Anthony M}, Date-Added = {2012-11-05 17:39:47 +0000}, Date-Modified = {2012-11-05 17:43:53 +0000}, Doi = {10.1523/JNEUROSCI.1411-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Decision Making; Attention; latency; Behavior; Neurophysiology; mouse; Neocortex; Cerebral Cortex}, Month = {Oct}, Number = {43}, Pages = {15142-7}, pmid = {23100435}, Pst = {ppublish}, Title = {Differences in Sensitivity to Neural Timing among Cortical Areas}, Volume = {32}, Year = {2012}, url = {papers/Yang_JNeurosci2012.pdf}} @article{Chan:2012, Abstract = {In humans, naturally acquired microchimerism has been observed in many tissues and organs. Fetal microchimerism, however, has not been investigated in the human brain. Microchimerism of fetal as well as maternal origin has recently been reported in the mouse brain. In this study, we quantified male DNA in the human female brain as a marker for microchimerism of fetal origin (i.e. acquisition of male DNA by a woman while bearing a male fetus). Targeting the Y-chromosome-specific DYS14 gene, we performed real-time quantitative PCR in autopsied brain from women without clinical or pathologic evidence of neurologic disease (n = 26), or women who had Alzheimer's disease (n = 33). We report that 63% of the females (37 of 59) tested harbored male microchimerism in the brain. Male microchimerism was present in multiple brain regions. Results also suggested lower prevalence (p = 0.03) and concentration (p = 0.06) of male microchimerism in the brains of women with Alzheimer's disease than the brains of women without neurologic disease. In conclusion, male microchimerism is frequent and widely distributed in the human female brain.}, Author = {Chan, William F N and Gurnot, C{\'e}cile and Montine, Thomas J and Sonnen, Joshua A and Guthrie, Katherine A and Nelson, J Lee}, Date-Added = {2012-11-05 17:39:47 +0000}, Date-Modified = {2012-11-05 17:43:13 +0000}, Doi = {10.1371/journal.pone.0045592}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {Genomic Imprinting; Fetal Development; Maternal-Fetal Exchange; Maternally-Acquired; Cell Fusion; macrophage; microglia; gene}, Number = {9}, Pages = {e45592}, Pmc = {PMC3458919}, pmid = {23049819}, Pst = {ppublish}, Title = {Male microchimerism in the human female brain}, Volume = {7}, Year = {2012}, url = {papers/Chan_PLoSOne2012.pdf}} @article{Johansson:2008, Abstract = {Transplanted bone marrow-derived cells (BMDCs) have been reported to fuse with cells of diverse tissues, but the extremely low frequency of fusion has led to the view that such events are biologically insignificant. Nonetheless, in mice with a lethal recessive liver disease (tyrosinaemia), transplantation of wild-type BMDCs restored liver function by cell fusion and prevented death, indicating that cell fusion can have beneficial effects. Here we report that chronic inflammation resulting from severe dermatitis or autoimmune encephalitis leads to robust fusion of BMDCs with Purkinje neurons and formation of hundreds of binucleate heterokaryons per cerebellum, a 10-100-fold higher frequency than previously reported. Single haematopoietic stem-cell transplants showed that the fusogenic cell is from the haematopoietic lineage and parabiosis experiments revealed that fusion can occur without irradiation. Transplantation of rat bone marrow into mice led to activation of dormant rat Purkinje neuron-specific genes in BMDC nuclei after fusion with mouse Purkinje neurons, consistent with nuclear reprogramming. The precise neurological role of these heterokaryons awaits elucidation, but their frequency in brain after inflammation is clearly much higher than previously appreciated.}, Author = {Johansson, Clas B and Youssef, Sawsan and Koleckar, Kassie and Holbrook, Colin and Doyonnas, Regis and Corbel, Stephane Y and Steinman, Lawrence and Rossi, Fabio M V and Blau, Helen M}, Date-Added = {2012-11-05 17:39:47 +0000}, Date-Modified = {2012-11-05 17:40:43 +0000}, Doi = {10.1038/ncb1720}, Journal = {Nat Cell Biol}, Journal-Full = {Nature cell biology}, Keywords = {Stem Cells; Cell Fusion; macrophage; microglia; neuron; Immune System;}, Mesh = {Animals; Bone Marrow Cells; Cell Fusion; Dermatitis; Encephalomyelitis, Autoimmune, Experimental; Female; Green Fluorescent Proteins; Hematopoietic Stem Cells; Inflammation; Lipopolysaccharides; Mesenchymal Stem Cell Transplantation; Mice; Mice, Inbred C57BL; Purkinje Cells; Rats; Rats, Sprague-Dawley; Transplantation Chimera}, Month = {May}, Number = {5}, Pages = {575-83}, pmid = {18425116}, Pst = {ppublish}, Title = {Extensive fusion of haematopoietic cells with Purkinje neurons in response to chronic inflammation}, Volume = {10}, Year = {2008}, url = {papers/Johansson_NatCellBiol2008.pdf}} @article{Lapray:2010, Abstract = {Previous reports indicate that in utero knockdown of doublecortin (DCX) results in the genesis of a subcortical heterotopia reminiscent of the doublecortex observed in female patients with DCX mutations. It has also been shown that these rats display an increased susceptibility to convulsant agents and increased cortical neurons excitability; but it is presently unknown whether they display spontaneous seizures. Furthermore, the link between the size of heterotopia and the clinical manifestation remained to be elucidated. Using video-electrocorticogram recordings, we now report that DCX knockdown induces frequent spontaneous seizures commonly associated with myoclonic jerks in adult rats. Surprisingly, epilepsy occurred even in rats with very small subcortical heterotopias, as revealed by histological analysis of recorded animals. Moreover, the severity of the epileptic manifestations was positively correlated with both the size of the subcortical heterotopia and the age of recorded animals; thus, epileptic features were not detected in immature affected rats. In conclusion, our data demonstrate for the first time that subtle alterations can yield epilepsy and reveal a strong correlation between thicknesses of subcortical heterotopia, age of affected individuals and clinical impairment.}, Author = {Lapray, Damien and Popova, Irina Y and Kindler, Jennifer and Jorquera, Isabel and Becq, H{\'e}l{\`e}ne and Manent, Jean-Bernard and Luhmann, Heiko J and Represa, Alfonso}, Date-Added = {2012-11-05 17:38:13 +0000}, Date-Modified = {2012-11-05 17:39:24 +0000}, Doi = {10.1093/cercor/bhq014}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {cortical malformation; Epilepsy; development; doublecortin; Seizures; Neurophysiology; rat}, Mesh = {Animals; Animals, Newborn; Disease Models, Animal; Epilepsy; Female; Gene Knockdown Techniques; Humans; Male; Malformations of Cortical Development; Microtubule-Associated Proteins; Neuropeptides; Rats; Rats, Wistar}, Month = {Nov}, Number = {11}, Pages = {2694-701}, pmid = {20164125}, Pst = {ppublish}, Title = {Spontaneous epileptic manifestations in a DCX knockdown model of human double cortex}, Volume = {20}, Year = {2010}, url = {papers/Lapray_CerebCortex2010.pdf}} @article{Grinevich:2009, Abstract = {The brain-specific immediate early gene Arc/Arg3.1 is induced in response to a variety of stimuli, including sensory and behavior-linked neural activity. Here we report the generation of transgenic mice, termed TgArc/Arg3.1-d4EGFP, expressing a 4-h half-life form of enhanced green fluorescent protein (d4EGFP) under the control of the Arc/Arg3.1 promoter. We show that d4EGFP-mediated fluorescence faithfully reports Arc/Arg3.1 induction in response to physiological, pathological and pharmacological stimuli, and that this fluorescence permits electrical recording from activated neurons in the live mouse. Moreover, the fluorescent Arc/Arg3.1 indicator revealed activity changes in circumscribed brain areas in distinct modes of stress and in a mouse model of Alzheimer's disease. These findings identify the TgArc/Arg3.1-d4EGFP mouse as a versatile tool to monitor Arc/Arg3.1 induction in neural circuits, both in vitro and in vivo.}, Author = {Grinevich, Valery and Kolleker, Alexander and Eliava, Marina and Takada, Naoki and Takuma, Hiroshi and Fukazawa, Yugo and Shigemoto, Ryuichi and Kuhl, Dietmar and Waters, Jack and Seeburg, Peter H and Osten, Pavel}, Date-Added = {2012-11-05 17:33:58 +0000}, Date-Modified = {2012-11-05 17:35:47 +0000}, Doi = {10.1016/j.jneumeth.2009.07.015}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {optical physiology; optical imaging; multiphoton; Immediate-Early Proteins; genes; Transcription Factors; Reporter/genetics; Transgenes; transgenic; mouse; in vivo; Technique; ideas; grants}, Mesh = {Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Brain; Cytoskeletal Proteins; Disease Models, Animal; Fluorescence; Green Fluorescent Proteins; Humans; Male; Mice; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Presenilin-1; Presenilin-2; Promoter Regions, Genetic; Protease Nexins; Receptors, Cell Surface; Stress, Physiological; Time Factors}, Month = {Oct}, Number = {1}, Pages = {25-36}, pmid = {19628007}, Pst = {ppublish}, Title = {Fluorescent Arc/Arg3.1 indicator mice: a versatile tool to study brain activity changes in vitro and in vivo}, Volume = {184}, Year = {2009}, url = {papers/Grinevich_JNeurosciMethods2009.pdf}} @article{Lam:2012, Abstract = {A variety of genetically encoded reporters use changes in fluorescence (or F{\"o}rster) resonance energy transfer (FRET) to report on biochemical processes in living cells. The standard genetically encoded FRET pair consists of CFPs and YFPs, but many CFP-YFP reporters suffer from low FRET dynamic range, phototoxicity from the CFP excitation light and complex photokinetic events such as reversible photobleaching and photoconversion. We engineered two fluorescent proteins, Clover and mRuby2, which are the brightest green and red fluorescent proteins to date and have the highest F{\"o}rster radius of any ratiometric FRET pair yet described. Replacement of CFP and YFP with these two proteins in reporters of kinase activity, small GTPase activity and transmembrane voltage significantly improves photostability, FRET dynamic range and emission ratio changes. These improvements enhance detection of transient biochemical events such as neuronal action-potential firing and RhoA activation in growth cones.}, Author = {Lam, Amy J and St-Pierre, Fran{\c c}ois and Gong, Yiyang and Marshall, Jesse D and Cranfill, Paula J and Baird, Michelle A and McKeown, Michael R and Wiedenmann, J{\"o}rg and Davidson, Michael W and Schnitzer, Mark J and Tsien, Roger Y and Lin, Michael Z}, Date-Added = {2012-11-05 17:30:58 +0000}, Date-Modified = {2012-11-05 17:33:08 +0000}, Doi = {10.1038/nmeth.2171}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {Technique; optical imaging; microscopy; FRET; Transgenes; Reporter/genetics; optical physiology; Neurophysiology;}, Month = {Oct}, Number = {10}, Pages = {1005-12}, Pmc = {PMC3461113}, pmid = {22961245}, Pst = {ppublish}, Title = {Improving FRET dynamic range with bright green and red fluorescent proteins}, Volume = {9}, Year = {2012}, url = {papers/Lam_NatMethods2012.pdf}} @article{Jones:2012, Abstract = {Noise is a major concern in circuits processing electrical signals, including neural circuits. There are many factors that influence how noise propagates through neural circuits, and there are few systems in which noise levels have been studied throughout a processing pathway. We recorded intracellularly from multiple stages of a sensory-motor pathway in the locust that detects approaching objects. We found that responses are more variable and that signal-to-noise ratios (SNRs) are lower further from the sensory periphery. SNRs remain low even with the use of stimuli for which the pathway is most selective and for which the neuron representing its final sensory level must integrate many synaptic inputs. Modeling of this neuron shows that variability in the strength of individual synaptic inputs within a large population has little effect on the variability of the spiking output. In contrast, jitter in the timing of individual inputs and spontaneous variability is important for shaping the responses to preferred stimuli. These results suggest that neural noise is inherent to the processing of visual stimuli signaling impending collision and contributes to shaping neural responses along this sensory-motor pathway.}, Annote = {Model and paper of looming response, large movement detector, nAchR, GABA, nicotinic: }, Author = {Jones, Peter W and Gabbiani, Fabrizio}, Date-Added = {2012-11-05 17:04:45 +0000}, Date-Modified = {2012-11-05 17:08:24 +0000}, Doi = {10.1152/jn.00607.2011}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Models; looming response; movement detector, nAchR, GABA, nicotinic; noise; Theoretical; Signal Processing; sensory-motor; topographic map; multimodal; locust; Insect; neuron; Electrophysiology; extracellular; Neurophysiology}, Mesh = {Analysis of Variance; Animals; Computer Simulation; Grasshoppers; Light; Membrane Potentials; Models, Neurological; Motion Perception; Nervous System; Photic Stimulation; Photoreceptor Cells, Invertebrate; Psychophysics; Reaction Time; Signal-To-Noise Ratio; Time Factors; Visual Pathways}, Month = {Feb}, Number = {4}, Pages = {1067-79}, Pmc = {PMC3289460}, pmid = {22114160}, Pst = {ppublish}, Title = {Impact of neural noise on a sensory-motor pathway signaling impending collision}, Volume = {107}, Year = {2012}, url = {papers/Jones_JNeurophysiol2012.pdf}, Bdsk-Url-1 = {http://senselab.med.yale.edu/modeldb/ShowModel.asp?model=144007&file=%5CLGMD%5Cjnphysiol2012%5Cparameter_comparison.rtf}} @article{Fan:2012, Abstract = {The vast majority of prenatal genetic testing requires invasive sampling. However, this poses a risk to the fetus, so one must make a decision that weighs the desire for genetic information against the risk of an adverse outcome due to hazards of the testing process. These issues are not required to be coupled, and it would be desirable to discover genetic information about the fetus without incurring a health risk. Here we demonstrate that it is possible to non-invasively sequence the entire prenatal genome. Our results show that molecular counting of parental haplotypes in maternal plasma by shotgun sequencing of maternal plasma DNA allows the inherited fetal genome to be deciphered non-invasively. We also applied the counting principle directly to each allele in the fetal exome by performing exome capture on maternal plasma DNA before shotgun sequencing. This approach enables non-invasive exome screening of clinically relevant and deleterious alleles that were paternally inherited or had arisen as de novo germline mutations, and complements the haplotype counting approach to provide a comprehensive view of the fetal genome. Non-invasive determination of the fetal genome may ultimately facilitate the diagnosis of all inherited and de novo genetic disease.}, Author = {Fan, H Christina and Gu, Wei and Wang, Jianbin and Blumenfeld, Yair J and El-Sayed, Yasser Y and Quake, Stephen R}, Date-Added = {2012-11-05 17:02:31 +0000}, Date-Modified = {2012-11-05 17:03:47 +0000}, Doi = {10.1038/nature11251}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {ideas; grants; Genomic Imprinting; Sequence Analysis; Fetal Development; shotgun sequencing; disease; marker}, Mesh = {Chromosomes, Human; DNA; Exome; Female; Fetus; Genome, Human; Haplotypes; Humans; Male; Pregnancy; Prenatal Diagnosis; Sensitivity and Specificity}, Month = {Jul}, Number = {7407}, Pages = {320-4}, pmid = {22763444}, Pst = {ppublish}, Title = {Non-invasive prenatal measurement of the fetal genome}, Volume = {487}, Year = {2012}, url = {papers/Fan_Nature2012.pdf}} @article{Campbell:2012, Abstract = {Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress) or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.}, Author = {Campbell, J Preston and Karolak, Matthew R and Ma, Yun and Perrien, Daniel S and Masood-Campbell, S Kathryn and Penner, Niki L and Munoz, Steve A and Zijlstra, Andries and Yang, Xiangli and Sterling, Julie A and Elefteriou, Florent}, Date-Added = {2012-11-05 16:58:27 +0000}, Date-Modified = {2012-11-05 17:00:12 +0000}, Doi = {10.1371/journal.pbio.1001363}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {neuron; Immune System; cancer; metastasis; macrophage; microglia; Cell Fusion; ideas}, Mesh = {Adrenergic beta-Antagonists; Animals; Bone Marrow Cells; Bone Neoplasms; Cell Movement; Female; Mammary Neoplasms, Experimental; Mice; Osteoblasts; Propranolol; Receptors, Adrenergic, beta-2; Signal Transduction; Stromal Cells; Sympathetic Nervous System}, Month = {Jul}, Number = {7}, Pages = {e1001363}, Pmc = {PMC3398959}, pmid = {22815651}, Pst = {ppublish}, Title = {Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice}, Volume = {10}, Year = {2012}, url = {papers/Campbell_PLoSBiol2012.pdf}} @article{Poil:2012, Abstract = {Criticality has gained widespread interest in neuroscience as an attractive framework for understanding the character and functional implications of variability in brain activity. The metastability of critical systems maximizes their dynamic range, storage capacity, and computational power. Power-law scaling-a hallmark of criticality-has been observed on different levels, e.g., in the distribution of neuronal avalanches in vitro and in vivo, but also in the decay of temporal correlations in behavioral performance and ongoing oscillations in humans. An unresolved issue is whether power-law scaling on different organizational levels in the brain-and possibly in other hierarchically organized systems-can be related. Here, we show that critical-state dynamics of avalanches and oscillations jointly emerge in a neuronal network model when excitation and inhibition is balanced. The oscillatory activity of the model was qualitatively similar to what is typically observed in recordings of human resting-state MEG. We propose that homeostatic plasticity mechanisms tune this balance in healthy brain networks, and that it is essential for critical behavior on multiple levels of neuronal organization with ensuing functional benefits. Based on our network model, we introduce a concept of multi-level criticality in which power-law scaling can emerge on multiple time scales in oscillating networks.}, Author = {Poil, Simon-Shlomo and Hardstone, Richard and Mansvelder, Huibert D and Linkenkaer-Hansen, Klaus}, Date-Added = {2012-11-05 16:56:48 +0000}, Date-Modified = {2012-11-05 16:57:54 +0000}, Doi = {10.1523/JNEUROSCI.5990-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread; Spontaneous activity; computation biology; Theoretical; oscillations; synchrony; human; MEG; Models}, Mesh = {Action Potentials; Brain; Computer Simulation; Humans; Models, Neurological; Nerve Net; Neural Inhibition; Neuronal Plasticity; Neurons}, Month = {Jul}, Number = {29}, Pages = {9817-23}, pmid = {22815496}, Pst = {ppublish}, Title = {Critical-state dynamics of avalanches and oscillations jointly emerge from balanced excitation/inhibition in neuronal networks}, Volume = {32}, Year = {2012}, url = {papers/Poil_JNeurosci2012.pdf}} @article{Danziger:2012, Abstract = {How does visual perception shape the way we coordinate movements? Recent studies suggest that the brain organizes movements based on minimizing reaching errors in the presence of motor and sensory noise. We present an alternative hypothesis in which movement trajectories also result from acquired knowledge about the geometrical properties of the object that the brain is controlling. To test this hypothesis, we asked human subjects to control a simulated kinematic linkage by continuous finger motion, a completely novel experience. This paradigm removed all biases arising from influences of limb dynamics and past experience. Subjects were exposed to two different types of visual feedback; some saw the entire simulated linkage and others saw only the moving extremity. Consistent with our hypothesis, subjects learned to move the simulated linkage along geodesic lines corresponding to the geometrical structure of the observed motion. Thus, optimizing final accuracy is not the unique determinant of trajectory formation.}, Author = {Danziger, Zachary and Mussa-Ivaldi, Ferdinando A}, Date-Added = {2012-11-05 16:55:31 +0000}, Date-Modified = {2012-11-05 16:56:25 +0000}, Doi = {10.1523/JNEUROSCI.5528-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {motor; map; topographic map; Perception; visual system; Motion Perception;human}, Mesh = {Biomechanics; Feedback, Sensory; Female; Fingers; Humans; Learning; Male; Motion Perception; Movement; Photic Stimulation; Psychomotor Performance; Visual Perception}, Month = {Jul}, Number = {29}, Pages = {9859-69}, Pmc = {PMC3437549}, pmid = {22815501}, Pst = {ppublish}, Title = {The influence of visual motion on motor learning}, Volume = {32}, Year = {2012}, url = {papers/Danziger_JNeurosci2012.pdf}} @article{Tang:2012, Abstract = {Recent computational and experimental work has shown that similar network performance can result from variable sets of synaptic and intrinsic properties. Because temperature is a global perturbation that differentially influences every biological process within the nervous system, one might therefore expect that individual animals would respond differently to temperature. Nonetheless, the phase relationships of the pyloric rhythm of the stomatogastric ganglion (STG) of the crab, Cancer borealis, are remarkably invariant between 7 and 23$\,^{\circ}$C (Tang et al., 2010). Here, we report that, when isolated STG preparations were exposed to more extreme temperature ranges, their networks became nonrhythmic, or "crashed", in a reversible fashion. Animals were acclimated for at least 3 weeks at 7, 11, or 19$\,^{\circ}$C. When networks from the acclimated animals were perturbed by acute physiologically relevant temperature ramps (11-23$\,^{\circ}$C), the network frequency and phase relationships were independent of the acclimation group. At high acute temperatures (>23$\,^{\circ}$C), circuits from the cold-acclimated animals produced less-regular pyloric rhythms than those from warm-acclimated animals. At high acute temperatures, phase relationships between pyloric neurons were more variable from animal to animal than at moderate acute temperatures, suggesting that individual differences across animals in intrinsic circuit parameters are revealed at high temperatures. This shows that individual and variable neuronal circuits can behave similarly in normal conditions, but their behavior may diverge when confronted with extreme external perturbations.}, Author = {Tang, Lamont S and Taylor, Adam L and Rinberg, Anatoly and Marder, Eve}, Date-Added = {2012-11-05 16:54:24 +0000}, Date-Modified = {2012-11-05 16:54:58 +0000}, Doi = {10.1523/JNEUROSCI.1443-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread; crab; motor; oscillations; synchrony; Spontaneous activity}, Mesh = {Acclimatization; Animals; Brachyura; Environment; Ganglia, Invertebrate; Neurons; Periodicity; Pylorus; Temperature}, Month = {Jul}, Number = {29}, Pages = {10075-85}, pmid = {22815521}, Pst = {ppublish}, Title = {Robustness of a rhythmic circuit to short- and long-term temperature changes}, Volume = {32}, Year = {2012}, url = {papers/Tang_JNeurosci2012.pdf}} @article{Nguyen:2012, Abstract = {Mutations in the X-linked gene, methyl-CpG binding protein 2 (Mecp2), underlie a wide range of neuropsychiatric disorders, most commonly, Rett Syndrome (RTT), a severe autism spectrum disorder that affects approximately one in 10,000 female live births. Because mutations in the Mecp2 gene occur in the germ cells with onset of neurological symptoms occurring in early childhood, the role of MeCP2 has been ascribed to brain maturation at a specific developmental window. Here, we show similar kinetics of onset and progression of RTT-like symptoms in mice, including lethality, if MeCP2 is removed postnatally during the developmental stage that coincides with RTT onset, or adult stage. For the first time, we show that brains that lose MeCP2 at these two different stages are actively shrinking, resulting in higher than normal neuronal cell density. Furthermore, we show that mature dendritic arbors of pyramidal neurons are severely retracted and dendritic spine density is dramatically reduced. In addition, hippocampal astrocytes have significantly less complex ramified processes. These changes accompany a striking reduction in the levels of several synaptic proteins, including CaMKII α/β, AMPA, and NMDA receptors, and the synaptic vesicle proteins Vglut and Synapsin, which represent critical modifiers of synaptic function and dendritic arbor structure. Importantly, the mRNA levels of these synaptic proteins remains unchanged, suggesting that MeCP2 likely regulates these synaptic proteins post-transcriptionally, directly or indirectly. Our data suggest a crucial role for MeCP2 in post-transcriptional regulation of critical synaptic proteins involved in maintaining mature neuronal networks during late stages of postnatal brain development.}, Author = {Nguyen, Minh Vu Chuong and Du, Fang and Felice, Christy A and Shan, Xiwei and Nigam, Aparna and Mandel, Gail and Robinson, John K and Ballas, Nurit}, Date-Added = {2012-11-05 16:52:21 +0000}, Date-Modified = {2012-11-05 16:53:19 +0000}, Doi = {10.1523/JNEUROSCI.1316-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {toread; mutant; mouse; transgenic; autism; Autistic Disorder; Behavior; Dendrites; spines;}, Mesh = {Animals; Brain; Dendrites; Disease Models, Animal; Gene Expression Regulation; Male; Methyl-CpG-Binding Protein 2; Mice; Mice, Transgenic; Motor Activity; Nerve Net; Neurons; Rett Syndrome; Synapses}, Month = {Jul}, Number = {29}, Pages = {10021-34}, Pmc = {PMC3461266}, pmid = {22815516}, Pst = {ppublish}, Title = {MeCP2 is critical for maintaining mature neuronal networks and global brain anatomy during late stages of postnatal brain development and in the mature adult brain}, Volume = {32}, Year = {2012}, url = {papers/Nguyen_JNeurosci2012.pdf}} @article{Litwin-Kumar:2012, Abstract = {Anatomical studies demonstrate that excitatory connections in cortex are not uniformly distributed across a network but instead exhibit clustering into groups of highly connected neurons. The implications of clustering for cortical activity are unclear. We studied the effect of clustered excitatory connections on the dynamics of neuronal networks that exhibited high spike time variability owing to a balance between excitation and inhibition. Even modest clustering substantially changed the behavior of these networks, introducing slow dynamics during which clusters of neurons transiently increased or decreased their firing rate. Consequently, neurons exhibited both fast spiking variability and slow firing rate fluctuations. A simplified model shows how stimuli bias networks toward particular activity states, thereby reducing firing rate variability as observed experimentally in many cortical areas. Our model thus relates cortical architecture to the reported variability in spontaneous and evoked spiking activity.}, Author = {Litwin-Kumar, Ashok and Doiron, Brent}, Date-Added = {2012-11-05 16:36:41 +0000}, Date-Modified = {2012-11-05 16:40:09 +0000}, Doi = {10.1038/nn.3220}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {oscillations; synchrony; connectivity; graph theory; Theoretical; Models; computation biology; Cerebral Cortex; Neocortex; network; Technique}, Month = {Sep}, Number = {11}, Pages = {1498-505}, pmid = {23001062}, Pst = {ppublish}, Title = {Slow dynamics and high variability in balanced cortical networks with clustered connections}, Volume = {15}, Year = {2012}, url = {papers/Litwin-Kumar_NatNeurosci2012.pdf}} @article{Wandell:2011, Abstract = {A quarter-century ago visual neuroscientists had little information about the number and organization of retinotopic maps in human visual cortex. The advent of functional magnetic resonance imaging (MRI), a non-invasive, spatially-resolved technique for measuring brain activity, provided a wealth of data about human retinotopic maps. Just as there are differences amongst non-human primate maps, the human maps have their own unique properties. Many human maps can be measured reliably in individual subjects during experimental sessions lasting less than an hour. The efficiency of the measurements and the relatively large amplitude of functional MRI signals in visual cortex make it possible to develop quantitative models of functional responses within specific maps in individual subjects. During this last quarter-century, there has also been significant progress in measuring properties of the human brain at a range of length and time scales, including white matter pathways, macroscopic properties of gray and white matter, and cellular and molecular tissue properties. We hope the next 25years will see a great deal of work that aims to integrate these data by modeling the network of visual signals. We do not know what such theories will look like, but the characterization of human retinotopic maps from the last 25years is likely to be an important part of future ideas about visual computations.}, Author = {Wandell, Brian A and Winawer, Jonathan}, Date-Added = {2012-11-02 18:18:52 +0000}, Date-Modified = {2012-11-02 18:20:03 +0000}, Doi = {10.1016/j.visres.2010.08.004}, Journal = {Vision Res}, Journal-Full = {Vision research}, Keywords = {visual system; fMRI; human; retinotopy; topographic map; visual cortex; Neocortex; function; review literature}, Mesh = {Brain Mapping; Humans; Magnetic Resonance Imaging; Visual Cortex; Visual Pathways}, Month = {Apr}, Number = {7}, Pages = {718-37}, Pmc = {PMC3030662}, pmid = {20692278}, Pst = {ppublish}, Title = {Imaging retinotopic maps in the human brain}, Volume = {51}, Year = {2011}, url = {papers/Wandell_VisionRes2011.pdf}} @article{Sengpiel:1999, Abstract = {Visual search tasks appear to involve spatially selective attention to the target, but evidence for attentional modulation in the visual area with the most precise retinotopic organization V1 has been elusive. Recent imaging studies show that spatial attention can indeed enhance visual responses in human V1.}, Author = {Sengpiel, F and H{\"u}bener, M}, Date-Added = {2012-11-02 18:13:41 +0000}, Date-Modified = {2012-11-02 18:14:21 +0000}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {visual system; topographic map; function; human; visual cortex; retinotopy; review literature}, Mesh = {Animals; Humans; Magnetic Resonance Imaging; Visual Cortex}, Month = {May}, Number = {9}, Pages = {R318-21}, pmid = {10419335}, Pst = {ppublish}, Title = {Visual attention: spotlight on the primary visual cortex}, Volume = {9}, Year = {1999}, url = {papers/Sengpiel_CurrBiol1999.pdf}} @article{Hoffmann:2012, Abstract = {The absence of the optic chiasm is an extraordinary and extreme abnormality in the nervous system. The abnormality produces highly atypical functional responses in the cortex, including overlapping hemifield representations and bilateral population receptive fields in both striate and extrastriate visual cortex. Even in the presence of these large functional abnormalities, the effect on visual perception and daily life is not easily detected. Here, we demonstrate that in two achiasmic humans the gross topography of the geniculostriate and occipital callosal connections remains largely unaltered. We conclude that visual function is preserved by reorganization of intracortical connections instead of large-scale reorganizations of the visual cortex. Thus, developmental mechanisms of local wiring within cortical maps compensate for the improper gross wiring to preserve function in human achiasma.}, Author = {Hoffmann, Michael B and Kaule, Falko R and Levin, Netta and Masuda, Yoichiro and Kumar, Anil and Gottlob, Irene and Horiguchi, Hiroshi and Dougherty, Robert F and Stadler, Joerg and Wolynski, Barbara and Speck, Oliver and Kanowski, Martin and Liao, Yaping J and Wandell, Brian A and Dumoulin, Serge O}, Date-Added = {2012-11-02 18:10:29 +0000}, Date-Modified = {2012-11-02 18:10:29 +0000}, Doi = {10.1016/j.neuron.2012.05.026}, Journal = {Neuron}, Journal-Full = {Neuron}, Mesh = {Humans; Magnetic Resonance Imaging; Neuronal Plasticity; Optic Chiasm; Visual Pathways}, Month = {Aug}, Number = {3}, Pages = {393-401}, Pmc = {PMC3427398}, pmid = {22884323}, Pst = {ppublish}, Title = {Plasticity and stability of the visual system in human achiasma}, Volume = {75}, Year = {2012}, url = {papers/Hoffmann_Neuron2012.pdf}, Bdsk-File-2 = {papers/Hoffmann_Neuron2012a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.05.026}} @article{Goddard:2012, Abstract = {Gamma-band (25-140 Hz) oscillations are a hallmark of sensory processing in the forebrain. The optic tectum (OT), a midbrain structure implicated in sensorimotor processing and attention, also exhibits gamma oscillations. However, the origin and mechanisms of these oscillations remain unknown. We discovered that in acute slices of the avian OT, persistent (>100 ms) epochs of large amplitude gamma oscillations can be evoked that closely resemble those recorded in vivo. We found that cholinergic, glutamatergic, and GABAergic mechanisms differentially regulate the structure of the oscillations at various timescales. These persistent oscillations originate in the multisensory layers of the OT and are broadcast to visual layers via the cholinergic nucleus Ipc, providing a potential mechanism for enhancing the processing of visual information within the OT. The finding that the midbrain contains an intrinsic gamma-generating circuit suggests that the OT could use its own oscillatory code to route signals to forebrain networks.}, Author = {Goddard, C Alex and Sridharan, Devarajan and Huguenard, John R and Knudsen, Eric I}, Date-Added = {2012-11-02 17:58:35 +0000}, Date-Modified = {2012-11-02 18:00:11 +0000}, Doi = {10.1016/j.neuron.2011.11.028}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optic tectum; visual system; Superior Colliculus; barn owl; multimodal; oscillations; synchrony; Attention; visual map;}, Mesh = {Animals; Animals, Newborn; Atropine; Attention; Biophysics; Brain Mapping; Chickens; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; GABA Modulators; Mesencephalon; Muscarinic Antagonists; Pentobarbital; Periodicity; Photic Stimulation; Picrotoxin; Receptors, Cholinergic; Receptors, GABA; Receptors, N-Methyl-D-Aspartate; Superior Colliculi; Synaptic Potentials; Valine}, Month = {Feb}, Number = {3}, Pages = {567-80}, Pmc = {PMC3291715}, pmid = {22325207}, Pst = {ppublish}, Title = {Gamma oscillations are generated locally in an attention-related midbrain network}, Volume = {73}, Year = {2012}, url = {papers/Goddard_Neuron2012.pdf}} @article{Park:2006, Author = {Park, Chan Young and Dolmetsch, Richard}, Date-Added = {2012-11-02 17:55:42 +0000}, Date-Modified = {2012-11-02 17:56:48 +0000}, Doi = {10.1126/science.1133757}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {development; Calcium Signaling/*physiology; review literature; Transcription Factors; toread}, Mesh = {Calcium; Calcium Channels; Calcium Signaling; Cell Membrane; Cytoplasm; Humans; Phospholipase C gamma; Protein Binding; Protein Structure, Tertiary; TRPC Cation Channels; Transcription Factors, TFII}, Month = {Oct}, Number = {5796}, Pages = {64-5}, pmid = {17023638}, Pst = {ppublish}, Title = {Cell signaling. The double life of a transcription factor takes it outside the nucleus}, Volume = {314}, Year = {2006}, url = {papers/Park_Science2006.pdf}} @article{Gomez-Ospina:2006, Abstract = {Voltage-gated calcium channels play a central role in regulating the electrical and biochemical properties of neurons and muscle cells. One of the ways in which calcium channels regulate long-lasting neuronal properties is by activating signaling pathways that control gene expression, but the mechanisms that link calcium channels to the nucleus are not well understood. We report that a C-terminal fragment of Ca(V)1.2, an L-type voltage-gated calcium channel (LTC), translocates to the nucleus and regulates transcription. We show that this calcium channel associated transcription regulator (CCAT) binds to a nuclear protein, associates with an endogenous promoter, and regulates the expression of a wide variety of endogenous genes important for neuronal signaling and excitability. The nuclear localization of CCAT is regulated both developmentally and by changes in intracellular calcium. These findings provide evidence that voltage-gated calcium channels can directly activate transcription and suggest a mechanism linking voltage-gated channels to the function and differentiation of excitable cells.}, Author = {Gomez-Ospina, Natalia and Tsuruta, Fuminori and Barreto-Chang, Odmara and Hu, Linda and Dolmetsch, Ricardo}, Date-Added = {2012-11-02 17:45:46 +0000}, Date-Modified = {2012-11-02 17:47:13 +0000}, Doi = {10.1016/j.cell.2006.10.017}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {Calcium Channels; Calcium Signaling; Transcription Factors; oscillations; toread; next; development}, Mesh = {Amino Acid Sequence; Animals; Calcium Channels, L-Type; Cell Culture Techniques; Cell Line; Cells, Cultured; Cerebral Cortex; Dendrites; Fluorescence Recovery After Photobleaching; Genes, Reporter; Humans; Ion Channel Gating; Luciferases; Myocytes, Cardiac; Neurites; Neurons; PC12 Cells; Rats; Rats, Sprague-Dawley; Transcription Factors; Transfection}, Month = {Nov}, Number = {3}, Pages = {591-606}, Pmc = {PMC1750862}, pmid = {17081980}, Pst = {ppublish}, Title = {The C terminus of the L-type voltage-gated calcium channel Ca(V)1.2 encodes a transcription factor}, Volume = {127}, Year = {2006}, url = {papers/Gomez-Ospina_Cell2006.pdf}, Bdsk-File-2 = {papers/Gomez-Ospina_Cell2006a.pdf}, Bdsk-File-3 = {papers/Gomez-Ospina_Cell2006b.pdf}} @article{Dolmetsch:1998, Abstract = {Cytosolic calcium ([Ca2+]i) oscillations are a nearly universal mode of signalling in excitable and non-excitable cells. Although Ca2+ is known to mediate a diverse array of cell functions, it is not known whether oscillations contribute to the efficiency or specificity of signalling or are merely an inevitable consequence of the feedback control of [Ca2+]i. We have developed a Ca2+ clamp technique to investigate the roles of oscillation amplitude and frequency in regulating gene expression driven by the proinflammatory transcription factors NF-AT, Oct/OAP and NF-kappaB. Here we report that oscillations reduce the effective Ca2+ threshold for activating transcription factors, thereby increasing signal detection at low levels of stimulation. In addition, specificity is encoded by the oscillation frequency: rapid oscillations stimulate all three transcription factors, whereas infrequent oscillations activate only NF-kappaB. The genes encoding the cytokines interleukin (IL)-2 and IL-8 are also frequency-sensitive in a way that reflects their degree of dependence on NF-AT versus NF-kappaB. Our results provide direct evidence that [Ca2+]i oscillations increase both the efficacy and the information content of Ca2+ signals that lead to gene expression and cell differentiation.}, Author = {Dolmetsch, R E and Xu, K and Lewis, R S}, Date-Added = {2012-11-02 17:40:26 +0000}, Date-Modified = {2012-11-02 17:41:21 +0000}, Doi = {10.1038/31960}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {development; Spontaneous activity; Calcium Channels; Calcium Signaling/*physiology; Transcription Factors; next; toread}, Mesh = {Calcium; Calcium Channels; Cell Membrane; Cytosol; DNA-Binding Proteins; Gene Expression Regulation; Genes, Reporter; Humans; Interleukin-2; Interleukin-8; Jurkat Cells; NF-kappa B; NFATC Transcription Factors; Nuclear Proteins; Phosphorylation; Signal Transduction; T-Lymphocytes; Transcription Factors; Transfection}, Month = {Apr}, Number = {6679}, Pages = {933-6}, pmid = {9582075}, Pst = {ppublish}, Title = {Calcium oscillations increase the efficiency and specificity of gene expression}, Volume = {392}, Year = {1998}, url = {papers/Dolmetsch_Nature1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/31960}} @article{Barreto-Chang:2009, Abstract = {Calcium imaging is a common technique that is useful for measuring calcium signals in cultured cells. Calcium imaging techniques take advantage of calcium indicator dyes, which are BAPTA-based organic molecules that change their spectral properties in response to the binding of Ca2+ ions. Calcium indicator dyes fall into two categories, ratio-metric dyes like Fura-2 and Indo-1 and single-wavelength dyes like Fluo-4. Ratio-metric dyes change either their excitation or their emission spectra in response to calcium, allowing the concentration of intracellular calcium to be determined from the ratio of fluorescence emission or excitation at distinct wavelengths. The main advantage of using ratio-metric dyes over single wavelength probes is that the ratio signal is independent of the dye concentration, illumination intensity, and optical path length allowing the concentration of intracellular calcium to be determined independently of these artifacts. One of the most common calcium indicators is Fura-2, which has an emission peak at 505 nM and changes its excitation peak from 340 nm to 380 nm in response to calcium binding. Here we describe the use of Fura-2 to measure intracellular calcium elevations in neurons and other excitable cells.}, Author = {Barreto-Chang, Odmara L and Dolmetsch, Ricardo E}, Date-Added = {2012-11-02 17:38:20 +0000}, Date-Modified = {2012-11-02 17:39:02 +0000}, Doi = {10.3791/1067}, Journal = {J Vis Exp}, Journal-Full = {Journal of visualized experiments : JoVE}, Keywords = {optical physiology; imaging; Technique; review literature; calcium imaging;}, Mesh = {Calcium; Calcium Signaling; Cerebral Cortex; Fluorescent Dyes; Fura-2; Microscopy, Fluorescence; Neurons}, Number = {23}, Pmc = {PMC2763293}, pmid = {19229178}, Pst = {epublish}, Title = {Calcium imaging of cortical neurons using Fura-2 AM}, Year = {2009}, Bdsk-Url-1 = {http://dx.doi.org/10.3791/1067}} @article{Rana:2010, Abstract = {Understanding the complexity of neuronal biology requires the manipulation of cellular processes with high specificity and spatio-temporal precision. The recent development of synthetic photo-activatable proteins designed using the light-oxygen-voltage and phytochrome domains provides a new set of tools for genetically targeted optical control of cell signaling. Their modular design, functional diversity, precisely controlled activity and in vivo applicability offer many advantages for investigating neuronal function. Although designing these proteins is still a considerable challenge, future advances in rational protein design and a deeper understanding of their photoactivation mechanisms will allow the development of the next generation of optogenetic techniques.}, Author = {Rana, Anshul and Dolmetsch, Ricardo E}, Date-Added = {2012-11-02 17:37:05 +0000}, Date-Modified = {2012-11-02 17:38:06 +0000}, Doi = {10.1016/j.conb.2010.08.018}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {optical physiology; imaging; gene; Technique; review literature; toread; activity manipulation;}, Mesh = {Animals; Gene Targeting; Humans; Luminescent Proteins; Neurons; Photochemistry; Rhodopsins, Microbial; Signal Transduction; Staining and Labeling}, Month = {Oct}, Number = {5}, Pages = {617-22}, Pmc = {PMC2993759}, pmid = {20850295}, Pst = {ppublish}, Title = {Using light to control signaling cascades in live neurons}, Volume = {20}, Year = {2010}, url = {papers/Rana_CurrOpinNeurobiol2010.pdf}} @article{Ackman:2012, Abstract = {The morphological and functional development of the vertebrate nervous system is initially governed by genetic factors and subsequently refined by neuronal activity. However, fundamental features of the nervous system emerge before sensory experience is possible. Thus, activity-dependent development occurring before the onset of experience must be driven by spontaneous activity, but the origin and nature of activity in vivo remains largely untested. Here we use optical methods to show in live neonatal mice that waves of spontaneous retinal activity are present and propagate throughout the entire visual system before eye opening. This patterned activity encompassed the visual field, relied on cholinergic neurotransmission, preferentially initiated in the binocular retina and exhibited spatiotemporal correlations between the two hemispheres. Retinal waves were the primary source of activity in the midbrain and primary visual cortex, but only modulated ongoing activity in secondary visual areas. Thus, spontaneous retinal activity is transmitted through the entire visual system and carries patterned information capable of guiding the activity-dependent development of complex intra- and inter-hemispheric circuits before the onset of vision.}, Author = {Ackman, James B and Burbridge, Timothy J and Crair, Michael C}, Date-Added = {2012-10-25 13:10:07 +0000}, Date-Modified = {2013-05-21 19:47:22 +0000}, Doi = {10.1038/nature11529}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Spontaneous activity; Retina; Visual Cortex; visual system; Superior Colliculus; optic tectum; optical imaging; optical physiology; calcium imaging; multiphoton; development; Neocortex; mirror symmetry; currOpinRvw}, Month = {Oct}, Number = {7419}, Pages = {219-25}, Pmc = {PMC3962269}, pmid = {23060192}, Pst = {ppublish}, Title = {Retinal waves coordinate patterned activity throughout the developing visual system}, Volume = {490}, Year = {2012}, url = {papers/Ackman_Nature2012.pdf}, Bdsk-File-2 = {papers/Ackman_Nature2012a.pdf}} @article{Just:2007, Abstract = {The brain activation of a group of high-functioning autistic participants was measured using functional magnetic resonance imaging during the performance of a Tower of London task, in comparison with a control group matched with respect to intelligent quotient, age, and gender. The 2 groups generally activated the same cortical areas to similar degrees. However, there were 3 indications of underconnectivity in the group with autism. First, the degree of synchronization (i.e., the functional connectivity or the correlation of the time series of the activation) between the frontal and parietal areas of activation was lower for the autistic than the control participants. Second, relevant parts of the corpus callosum, through which many of the bilaterally activated cortical areas communicate, were smaller in cross-sectional area in the autistic participants. Third, within the autism group but not within the control group, the size of the genu of the corpus callosum was correlated with frontal-parietal functional connectivity. These findings suggest that the neural basis of altered cognition in autism entails a lower degree of integration of information across certain cortical areas resulting from reduced intracortical connectivity. The results add support to a new theory of cortical underconnectivity in autism, which posits a deficit in integration of information at the neural and cognitive levels.}, Author = {Just, Marcel Adam and Cherkassky, Vladimir L and Keller, Timothy A and Kana, Rajesh K and Minshew, Nancy J}, Date-Added = {2012-10-14 04:29:25 +0000}, Date-Modified = {2012-10-14 04:30:01 +0000}, Doi = {10.1093/cercor/bhl006}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {autism; Autistic Disorder; connectivity; default mode network; human; fMRI}, Mesh = {Adult; Autistic Disorder; Brain Mapping; Cerebral Cortex; Cognition; Corpus Callosum; Female; Humans; Magnetic Resonance Imaging; Male; Neural Pathways}, Month = {Apr}, Number = {4}, Pages = {951-61}, pmid = {16772313}, Pst = {ppublish}, Title = {Functional and anatomical cortical underconnectivity in autism: evidence from an FMRI study of an executive function task and corpus callosum morphometry}, Volume = {17}, Year = {2007}, url = {papers/Just_CerebCortex2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhl006}} @article{Demonet:2004, Abstract = {Developmental dyslexia, or specific reading disability, is a disorder in which children with normal intelligence and sensory abilities show learning deficits for reading. Substantial evidence has established its biological origin and the preponderance of phonological disorders even though important phenotypic variability and comorbidity have been recorded. Diverse theories have been proposed to account for the cognitive and neurological aspects of dyslexia. Findings of genetic studies show that different loci affect specific reading disability although a direct relation has not been established between symptoms and a given genomic locus. In both children and adults with dyslexia, results of neuroimaging studies suggest defective activity and abnormal connectivity between regions crucial for language functions--eg, the left fusiform gyrus for reading--and changes in brain activity associated with performance improvement after various remedial interventions.}, Author = {D{\'e}monet, Jean-Fran{\c c}ois and Taylor, Margot J and Chaix, Yves}, Date-Added = {2012-10-13 21:46:13 +0000}, Date-Modified = {2012-10-13 21:46:39 +0000}, Doi = {10.1016/S0140-6736(04)16106-0}, Journal = {Lancet}, Journal-Full = {Lancet}, Keywords = {Dyslexia; neurological disorder; human; connectivity; Neocortex; Cerebral Cortex}, Mesh = {Adult; Brain Mapping; Child; Dyslexia; Humans; Reading}, Month = {May}, Number = {9419}, Pages = {1451-60}, pmid = {15121410}, Pst = {ppublish}, Title = {Developmental dyslexia}, Volume = {363}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0140-6736(04)16106-0}} @article{Egaas:1995, Abstract = {OBJECTIVE: To determine via magnetic resonance imaging if the posterior corpus callosum is reduced in the midline cross-sectional area in autistic patients, consistent with previous reports of parietal lobe abnormalities. DESIGN: Case-control study. SETTING: Tertiary care facility. PATIENTS AND OTHER PARTICIPANTS: Fifty-one autistic patients (45 males and six females; age range, 3 to 42 years), including both mentally retarded and nonretarded patients who met several diagnostic criteria for autism were prospectively selected. Fifty-one age-and sex-matched volunteer normal control subjects were also included. INTERVENTION: None. MAIN OUTCOME MEASURES: Computer-aided measurement of cross-sectional area, areas of five subregions, and thickness profile. RESULTS: Overall size reduction, concentrated in posterior subregions. CONCLUSIONS: Evidence is found of a reduced size of the corpus callosum in autistic patients. This reduction is localized to posterior regions, where parietal lobe fibers are known to project. This finding further supports the idea that parietal lobe involvement may be a consistent feature in autism.}, Author = {Egaas, B and Courchesne, E and Saitoh, O}, Date-Added = {2012-10-13 21:43:18 +0000}, Date-Modified = {2012-10-13 21:44:01 +0000}, Journal = {Arch Neurol}, Journal-Full = {Archives of neurology}, Keywords = {Autistic Disorder; autism; Cerebral Cortex; Neocortex; connectivity; human}, Mesh = {Adolescent; Adult; Autistic Disorder; Cerebral Cortex; Child; Child, Preschool; Corpus Callosum; Female; Humans; Magnetic Resonance Imaging; Male}, Month = {Aug}, Number = {8}, Pages = {794-801}, pmid = {7639631}, Pst = {ppublish}, Title = {Reduced size of corpus callosum in autism}, Volume = {52}, Year = {1995}, url = {papers/Egaas_ArchNeurol1995.pdf}} @article{Castelli:2002, Abstract = {Ten able adults with autism or Asperger syndrome and 10 normal volunteers were PET scanned while watching animated sequences. The animations depicted two triangles moving about on a screen in three different conditions: moving randomly, moving in a goal-directed fashion (chasing, fighting), and moving interactively with implied intentions (coaxing, tricking). The last condition frequently elicited descriptions in terms of mental states that viewers attributed to the triangles (mentalizing). The autism group gave fewer and less accurate descriptions of these latter animations, but equally accurate descriptions of the other animations compared with controls. While viewing animations that elicited mentalizing, in contrast to randomly moving shapes, the normal group showed increased activation in a previously identified mentalizing network (medial prefrontal cortex, superior temporal sulcus at the temporo-parietal junction and temporal poles). The autism group showed less activation than the normal group in all these regions. However, one additional region, extrastriate cortex, which was highly active when watching animations that elicited mentalizing, showed the same amount of increased activation in both groups. In the autism group this extrastriate region showed reduced functional connectivity with the superior temporal sulcus at the temporo-parietal junction, an area associated with the processing of biological motion as well as with mentalizing. This finding suggests a physiological cause for the mentalizing dysfunction in autism: a bottleneck in the interaction between higher order and lower order perceptual processes.}, Author = {Castelli, Fulvia and Frith, Chris and Happ{\'e}, Francesca and Frith, Uta}, Date-Added = {2012-10-13 21:43:16 +0000}, Date-Modified = {2012-10-13 21:44:10 +0000}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {Autistic Disorder; autism; Cerebral Cortex; Neocortex; connectivity; human}, Mesh = {Adult; Asperger Syndrome; Autistic Disorder; Brain; Brain Mapping; Educational Status; Humans; Magnetic Resonance Imaging; Mental Status Schedule; Organ Specificity; Speech; Tomography, Emission-Computed}, Month = {Aug}, Number = {Pt 8}, Pages = {1839-49}, pmid = {12135974}, Pst = {ppublish}, Title = {Autism, Asperger syndrome and brain mechanisms for the attribution of mental states to animated shapes}, Volume = {125}, Year = {2002}} @article{Pignatelli:2009, Abstract = {A significant fraction of the interneurons added in adulthood to the glomerular layer (GL) of the olfactory bulb (OB) are dopaminergic (DA). In the OB, DA neurons are restricted to the GL, but using transgenic mice expressing eGFP under the tyrosine hydroxylase (TH) promoter, we also detected the presence of TH-GFP+ cells in the mitral and external plexiform layers. We hypothesized that these could be adult-generated neurons committed to become DA but not yet entirely differentiated. Accordingly, TH-GFP+ cells outside the GL exhibit functional properties (appearance of pacemaker currents, synaptic connection with the olfactory nerve, intracellular chloride concentration, and other) marking a gradient of maturity toward the dopaminergic phenotype along the mitral-glomerular axis. Finally, we propose that the establishment of a synaptic contact with the olfactory nerve is the key event allowing these cells to complete their differentiation toward the DA phenotype and to reach their final destination.}, Author = {Pignatelli, Angela and Ackman, James B and Vigetti, Davide and Beltrami, Antonio P and Zucchini, Silvia and Belluzzi, Ottorino}, Date-Added = {2012-10-02 20:56:24 +0000}, Date-Modified = {2012-10-02 20:56:24 +0000}, Doi = {10.1007/s00424-008-0535-0}, Journal = {Pflugers Arch}, Journal-Full = {Pfl{\"u}gers Archiv : European journal of physiology}, Mesh = {Action Potentials; Animals; Chlorides; Dopamine; Eye Proteins; Homeodomain Proteins; Mice; Mice, Transgenic; Neurons; Olfactory Bulb; Paired Box Transcription Factors; Patch-Clamp Techniques; Receptors, Glutamate; Recombinant Fusion Proteins; Repressor Proteins; Tyrosine 3-Monooxygenase}, Month = {Feb}, Number = {4}, Pages = {899-915}, pmid = {19011893}, Pst = {ppublish}, Title = {A potential reservoir of immature dopaminergic replacement neurons in the adult mammalian olfactory bulb}, Volume = {457}, Year = {2009}, url = {papers/Pignatelli_PflugersArch2009.pdf}} @article{Wei:2012, Abstract = {Neural activity-induced long-term potentiation (LTP) of synaptic transmission is believed to be one of the cellular mechanisms underlying experience-dependent developmental refinement of neural circuits. Although it is well established that visual experience and neural activity are critical for the refinement of retinal circuits, whether and how LTP occurs in the retina remain unknown. Using in vivo perforated whole-cell recording and two-photon calcium imaging, we find that both repeated electrical and visual stimulations can induce LTP at excitatory synapses formed by bipolar cells on retinal ganglion cells in larval but not juvenile zebrafish. LTP induction requires the activation of postsynaptic N-methyl-D-aspartate receptors, and its expression involves arachidonic acid-dependent presynaptic changes in calcium dynamics and neurotransmitter release. Physiologically, both electrical and visual stimulation-induced LTP can enhance visual responses of retinal ganglion cells. Thus, LTP exists in developing retinae with a presynaptic locus and may serve for visual experience-dependent refinement of retinal circuits.}, Author = {Wei, Hong-Ping and Yao, Yuan-Yuan and Zhang, Rong-Wei and Zhao, Xiao-Feng and Du, Jiu-Lin}, Date-Added = {2012-09-04 18:21:22 +0000}, Date-Modified = {2012-09-04 18:23:36 +0000}, Doi = {10.1016/j.neuron.2012.05.031}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Long-Term Potentiation; synapse formation; activity manipulation; Zebrafish; in vivo; Synaptic Transmission; 21 Activity-development; calcium imaging; Patch-Clamp Techniques; N-Methyl-D-Aspartate; NMDA; plasticity}, Month = {Aug}, Number = {3}, Pages = {479-89}, pmid = {22884331}, Pst = {ppublish}, Title = {Activity-induced long-term potentiation of excitatory synapses in developing zebrafish retina in vivo}, Volume = {75}, Year = {2012}, url = {papers/Wei_Neuron2012.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2012.05.031}} @article{Hansel:2012, Abstract = {Neurons in primary visual cortex (V1) display substantial orientation selectivity even in species where V1 lacks an orientation map, such as in mice and rats. The mechanism underlying orientation selectivity in V1 with such a salt-and-pepper organization is unknown; it is unclear whether a connectivity that depends on feature similarity is required, or a random connectivity suffices. Here we argue for the latter. We study the response to a drifting grating of a network model of layer 2/3 with random recurrent connectivity and feedforward input from layer 4 neurons with random preferred orientations. We show that even though the total feedforward and total recurrent excitatory and inhibitory inputs all have a very weak orientation selectivity, strong selectivity emerges in the neuronal spike responses if the network operates in the balanced excitation/inhibition regime. This is because in this regime the (large) untuned components in the excitatory and inhibitory contributions approximately cancel. As a result the untuned part of the input into a neuron as well as its modulation with orientation and time all have a size comparable to the neuronal threshold. However, the tuning of the F0 and F1 components of the input are uncorrelated and the high-frequency fluctuations are not tuned. This is reflected in the subthreshold voltage response. Remarkably, due to the nonlinear voltage-firing rate transfer function, the preferred orientation of the F0 and F1 components of the spike response are highly correlated.}, Author = {Hansel, David and van Vreeswijk, Carl}, Date-Added = {2012-09-04 18:17:35 +0000}, Date-Modified = {2012-09-04 18:19:51 +0000}, Doi = {10.1523/JNEUROSCI.6284-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {visual system; visual cortex; Neocortex; mouse; rat; Orientation; topographic map; sensory map; function; self organization; oscillations; Neurophysiology; extracellular; Models; Theoretical; Computational Biology; connectivity}, Mesh = {Action Potentials; Algorithms; Animals; Biophysical Processes; Computer Simulation; Excitatory Postsynaptic Potentials; Models, Neurological; Nerve Net; Neural Inhibition; Neurons; Nonlinear Dynamics; Orientation; Visual Cortex; Visual Pathways}, Month = {Mar}, Number = {12}, Pages = {4049-64}, pmid = {22442071}, Pst = {ppublish}, Title = {The mechanism of orientation selectivity in primary visual cortex without a functional map}, Volume = {32}, Year = {2012}, url = {papers/Hansel_JNeurosci2012.pdf}} @article{Triplett:2012, Abstract = {The superior colliculus (SC) is a midbrain structure that integrates visual, somatosensory, and auditory inputs to direct head and eye movements. Each of these modalities is topographically mapped and aligned with the others to ensure precise behavioral responses to multimodal stimuli. While it is clear that neural activity is instructive for topographic alignment of inputs from the visual cortex (V1) and auditory system with retinal axons in the SC, there is also evidence that activity-independent mechanisms are used to establish topographic alignment between modalities. Here, we show that the topography of the projection from primary somatosensory cortex (S1) to the SC is established during the first postnatal week. Unlike V1-SC projections, the S1-SC projection does not bifurcate when confronted with a duplicated retinocollicular map, showing that retinal input in the SC does not influence the topography of the S1-SC projection. However, S1-SC topography is disrupted in mice lacking ephrin-As, which we find are expressed in graded patterns along with their binding partners, the EphA4 and EphA7, in both S1 and the somatosensory recipient layer of the SC. Together, these data support a model in which somatosensory inputs into the SC map topographically and establish alignment with visual inputs in the SC using a gradient-matching mechanism.}, Author = {Triplett, Jason W and Phan, An and Yamada, Jena and Feldheim, David A}, Date-Added = {2012-09-04 18:13:53 +0000}, Date-Modified = {2012-09-04 18:17:25 +0000}, Doi = {10.1523/JNEUROSCI.0240-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retinal waves; Spontaneous activity; Superior Colliculus; optic tectum; function; topographic map; sensory map; Somatosensory Cortex; activity manipulation; Gene Expression; Eph Family; Ephrin-A4; multimodal; Mouse; 21 Activity-development; synapse formation; development; 21 Activity-development; visual system; retina}, Mesh = {Animals; Axons; Brain Mapping; Ephrins; Female; Image Processing, Computer-Assisted; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Microscopy, Fluorescence; Motor Cortex; Sensation; Somatosensory Cortex; Superior Colliculi; Visual Cortex; Visual Pathways}, Month = {Apr}, Number = {15}, Pages = {5264-71}, Pmc = {PMC3342701}, pmid = {22496572}, Pst = {ppublish}, Title = {Alignment of multimodal sensory input in the superior colliculus through a gradient-matching mechanism}, Volume = {32}, Year = {2012}, url = {papers/Triplett_JNeurosci2012.pdf}} @article{Gutknecht:2012, Abstract = {Brain serotonin (5-HT) is implicated in a wide range of functions from basic physiological mechanisms to complex behaviors, including neuropsychiatric conditions, as well as in developmental processes. Increasing evidence links 5-HT signaling alterations during development to emotional dysregulation and psychopathology in adult age. To further analyze the importance of brain 5-HT in somatic and brain development and function, and more specifically differentiation and specification of the serotonergic system itself, we generated a mouse model with brain-specific 5-HT deficiency resulting from a genetically driven constitutive inactivation of neuronal tryptophan hydroxylase-2 (Tph2). Tph2 inactivation (Tph2-/-) resulted in brain 5-HT deficiency leading to growth retardation and persistent leanness, whereas a sex- and age-dependent increase in body weight was observed in Tph2+/- mice. The conserved expression pattern of the 5-HT neuron-specific markers (except Tph2 and 5-HT) demonstrates that brain 5-HT synthesis is not a prerequisite for the proliferation, differentiation and survival of raphe neurons subjected to the developmental program of serotonergic specification. Furthermore, although these neurons are unable to synthesize 5-HT from the precursor tryptophan, they still display electrophysiological properties characteristic of 5-HT neurons. Moreover, 5-HT deficiency induces an up-regulation of 5-HT(1A) and 5-HT(1B) receptors across brain regions as well as a reduction of norepinephrine concentrations accompanied by a reduced number of noradrenergic neurons. Together, our results characterize developmental, neurochemical, neurobiological and electrophysiological consequences of brain-specific 5-HT deficiency, reveal a dual dose-dependent role of 5-HT in body weight regulation and show that differentiation of serotonergic neuron phenotype is independent from endogenous 5-HT synthesis.}, Author = {Gutknecht, Lise and Araragi, Naozumi and Merker, S{\"o}ren and Waider, Jonas and Sommerlandt, Frank M J and Mlinar, Boris and Baccini, Gilda and Mayer, Ute and Proft, Florian and Hamon, Michel and Schmitt, Angelika G and Corradetti, Renato and Lanfumey, Laurence and Lesch, Klaus-Peter}, Date-Added = {2012-08-31 21:14:38 +0000}, Date-Modified = {2012-08-31 21:14:43 +0000}, Doi = {10.1371/journal.pone.0043157}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {autism; Autistic Disorder; Serotonin; mouse; mice; development;}, Number = {8}, Pages = {e43157}, Pmc = {PMC3422228}, pmid = {22912815}, Pst = {ppublish}, Title = {Impacts of Brain Serotonin Deficiency following Tph2 Inactivation on Development and Raphe Neuron Serotonergic Specification}, Volume = {7}, Year = {2012}, url = {papers/Gutknecht_PLoSOne2012.pdf}} @article{Farook:2012, Abstract = {Childhood neurodevelopmental disorders like Angelman syndrome and autism may be the result of underlying defects in neuronal plasticity and ongoing problems with synaptic signaling. Some of these defects may be due to abnormal monoamine levels in different regions of the brain. Ube3a, a gene that causes Angelman syndrome (AS) when maternally deleted and is associated with autism when maternally duplicated has recently been shown to regulate monoamine synthesis in the Drosophila brain. Therefore, we examined monoamine levels in striatum, ventral midbrain, frontal cerebral cortex, cerebellar cortex and hippocampus in Ube3a deficient and Ube3a duplication animals. We found that serotonin (5HT), a monoamine affected in autism, was elevated in the striatum and cortex of AS mice. Dopamine levels were almost uniformly elevated compared to control littermates in the striatum, midbrain and frontal cortex regardless of genotype in Ube3a deficient and Ube3a duplication animals. In the duplication 15q autism mouse model, paternal but not maternal duplication animals showed a decrease in 5HT levels when compared to their wild type littermates, in accordance with previously published data. However, maternal duplication animals show no significant changes in 5HT levels throughout the brain. These abnormal monoamine levels could be responsible for many of the behavioral abnormalities observed in both AS and autism, but further investigation is required to determine if any of these changes are purely dependent on Ube3a levels in the brain.}, Author = {Farook, M Febin and Decuypere, Michael and Hyland, Keith and Takumi, Toru and Ledoux, Mark S and Reiter, Lawrence T}, Date-Added = {2012-08-31 21:13:17 +0000}, Date-Modified = {2012-08-31 21:14:05 +0000}, Doi = {10.1371/journal.pone.0043030}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {autism; Autistic Disorder; Serotonin; mouse; mice; development;}, Number = {8}, Pages = {e43030}, Pmc = {PMC3420863}, pmid = {22916201}, Pst = {ppublish}, Title = {Altered serotonin, dopamine and norepinepherine levels in 15q duplication and angelman syndrome mouse models}, Volume = {7}, Year = {2012}, url = {papers/Farook_PLoSOne2012.pdf}} @article{Ye:2012, Abstract = {BACKGROUND: Cross-modal plasticity is characterized as the hypersensitivity of remaining modalities after a sensory function is lost in rodents, which ensures their awareness to environmental changes. Cellular and molecular mechanisms underlying cross-modal sensory plasticity remain unclear. We aim to study the role of different types of neurons in cross-modal plasticity. METHODOLOGY/PRINCIPAL FINDINGS: In addition to behavioral tasks in mice, whole-cell recordings at the excitatory and inhibitory neurons, and their two-photon imaging, were conducted in piriform cortex. We produced a mouse model of cross-modal sensory plasticity that olfactory function was upregulated by trimming whiskers to deprive their sensory inputs. In the meantime of olfactory hypersensitivity, pyramidal neurons and excitatory synapses were functionally upregulated, as well as GABAergic cells and inhibitory synapses were downregulated in piriform cortex from the mice of cross-modal sensory plasticity, compared with controls. A crosswire connection between barrel cortex and piriform cortex was established in cross-modal plasticity. CONCLUSION/SIGNIFICANCE: An upregulation of pyramidal neurons and a downregulation of GABAergic neurons strengthen the activities of neuronal networks in piriform cortex, which may be responsible for olfactory hypersensitivity after a loss of whisker tactile input. This finding provides the clues for developing therapeutic strategies to promote sensory recovery and substitution.}, Author = {Ye, Bing and Huang, Li and Gao, Zilong and Chen, Ping and Ni, Hong and Guan, Sudong and Zhu, Yan and Wang, Jin-Hui}, Date-Added = {2012-08-31 21:02:04 +0000}, Date-Modified = {2012-08-31 21:06:00 +0000}, Doi = {10.1371/journal.pone.0041986}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {optical physiology; optical imaging; calcium imaging; Patch-Clamp Techniques; Neurophysiology; multimodal; Sensory Deprivation; sensory map; Somatosensory Cortex; piriform cortex; Neocortex; GABA; interneurons; mice; Mouse; in vitro}, Number = {8}, Pages = {e41986}, Pmc = {PMC3424151}, pmid = {22927919}, Pst = {ppublish}, Title = {The functional upregulation of piriform cortex is associated with cross-modal plasticity in loss of whisker tactile inputs}, Volume = {7}, Year = {2012}, url = {papers/Ye_PLoSOne2012.pdf}} @article{Stetter:2012, Abstract = {A systematic assessment of global neural network connectivity through direct electrophysiological assays has remained technically infeasible, even in simpler systems like dissociated neuronal cultures. We introduce an improved algorithmic approach based on Transfer Entropy to reconstruct structural connectivity from network activity monitored through calcium imaging. We focus in this study on the inference of excitatory synaptic links. Based on information theory, our method requires no prior assumptions on the statistics of neuronal firing and neuronal connections. The performance of our algorithm is benchmarked on surrogate time series of calcium fluorescence generated by the simulated dynamics of a network with known ground-truth topology. We find that the functional network topology revealed by Transfer Entropy depends qualitatively on the time-dependent dynamic state of the network (bursting or non-bursting). Thus by conditioning with respect to the global mean activity, we improve the performance of our method. This allows us to focus the analysis to specific dynamical regimes of the network in which the inferred functional connectivity is shaped by monosynaptic excitatory connections, rather than by collective synchrony. Our method can discriminate between actual causal influences between neurons and spurious non-causal correlations due to light scattering artifacts, which inherently affect the quality of fluorescence imaging. Compared to other reconstruction strategies such as cross-correlation or Granger Causality methods, our method based on improved Transfer Entropy is remarkably more accurate. In particular, it provides a good estimation of the excitatory network clustering coefficient, allowing for discrimination between weakly and strongly clustered topologies. Finally, we demonstrate the applicability of our method to analyses of real recordings of in vitro disinhibited cortical cultures where we suggest that excitatory connections are characterized by an elevated level of clustering compared to a random graph (although not extreme) and can be markedly non-local.}, Author = {Stetter, Olav and Battaglia, Demian and Soriano, Jordi and Geisel, Theo}, Date-Added = {2012-08-31 20:59:59 +0000}, Date-Modified = {2012-08-31 21:01:15 +0000}, Doi = {10.1371/journal.pcbi.1002653}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {graph theory; Theoretical; Computational Biology; Methods; optical imaging; Neurophysiology; calcium imaging; Statistics; Mathematics; network}, Month = {Aug}, Number = {8}, Pages = {e1002653}, Pmc = {PMC3426566}, pmid = {22927808}, Pst = {ppublish}, Title = {Model-free reconstruction of excitatory neuronal connectivity from calcium imaging signals}, Volume = {8}, Year = {2012}, url = {papers/Stetter_PLoSComputBiol2012.pdf}} @article{Carver:2012, Abstract = {Examining real-time cortical dynamics is crucial for understanding time perception. Using magnetoencephalography we studied auditory duration discrimination of short (<.5 s) versus long tones (>.5 s) versus a pitch control. Time-frequency analysis of event-related fields showed widespread beta-band (13-30 Hz) desynchronization during all tone presentations. Synthetic aperture magnetometry indicated automatic primarily sensorimotor responses in short and pitch conditions, with activation specific to timing in bilateral inferior frontal gyrus. In the long condition, a right lateralized network was active, including lateral prefrontal cortices, inferior frontal gyrus, supramarginal gyrus and secondary auditory areas. Activation in this network peaked just after attention to tone duration was no longer necessary, suggesting a role in sustaining representation of the interval. These data expand our understanding of time perception by revealing its complex cortical spatiotemporal signature.}, Author = {Carver, Frederick W and Elvev{\aa}g, Brita and Altamura, Mario and Weinberger, Daniel R and Coppola, Richard}, Date-Added = {2012-08-31 20:58:06 +0000}, Date-Modified = {2012-08-31 20:59:48 +0000}, Doi = {10.1371/journal.pone.0042618}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {entrainment; 21 Cortical oscillations; 21 Neurophysiology; Theoretical; Stimulation; Perception; Cognition; MEG; Auditory Cortex}, Number = {8}, Pages = {e42618}, Pmc = {PMC3422225}, pmid = {22912714}, Pst = {ppublish}, Title = {The neuromagnetic dynamics of time perception}, Volume = {7}, Year = {2012}, url = {papers/Carver_PLoSOne2012.pdf}} @article{Kozorovitskiy:2012, Abstract = {Neural activity during development critically shapes postnatal wiring of the mammalian brain. This is best illustrated by the sensory systems, in which the patterned feed-forward excitation provided by sensory organs and experience drives the formation of mature topographic circuits capable of extracting specific features of sensory stimuli. In contrast, little is known about the role of early activity in the development of the basal ganglia, a phylogenetically ancient group of nuclei fundamentally important for complex motor action and reward-based learning. These nuclei lack direct sensory input and are only loosely topographically organized, forming interlocking feed-forward and feed-back inhibitory circuits without laminar structure. Here we use transgenic mice and viral gene transfer methods to modulate neurotransmitter release and neuronal activity in vivo in the developing striatum. We find that the balance of activity between the two inhibitory and antagonist pathways in the striatum regulates excitatory innervation of the basal ganglia during development. These effects indicate that the propagation of activity through a multi-stage network regulates the wiring of the basal ganglia, revealing an important role of positive feedback in driving network maturation.}, Author = {Kozorovitskiy, Yevgenia and Saunders, Arpiar and Johnson, Caroline A and Lowell, Bradford B and Sabatini, Bernardo L}, Date-Added = {2012-08-28 14:21:04 +0000}, Date-Modified = {2012-08-28 14:29:10 +0000}, Doi = {10.1038/nature11052}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {activity manipulation; 21 Activity-development; 21 Neurophysiology; striatum; Basal Ganglia; mouse; Patch-Clamp Techniques; synapse formation; gaba; interneurons;}, Mesh = {Animals; Basal Ganglia; Cerebral Cortex; Feedback, Physiological; Female; Male; Mice; Mice, Transgenic; Models, Neurological; Neostriatum; Neural Inhibition; Neural Pathways; Synapses; Thalamus; Vesicular Inhibitory Amino Acid Transport Proteins; gamma-Aminobutyric Acid}, Month = {May}, Number = {7400}, Pages = {646-50}, Pmc = {PMC3367801}, pmid = {22660328}, Pst = {epublish}, Title = {Recurrent network activity drives striatal synaptogenesis}, Volume = {485}, Year = {2012}, url = {papers/Kozorovitskiy_Nature2012.pdf}, Bdsk-File-2 = {papers/Kozorovitskiy_Nature2012a.pdf}} @article{Geschwind:1965, Author = {Geschwind, N}, Date-Added = {2012-08-27 16:34:58 +0000}, Date-Modified = {2012-08-27 16:39:03 +0000}, Journal = {Brain}, Journal-Full = {Brain : a journal of neurology}, Keywords = {neurological disorder; Cognitive neuroscience; human; connectivity; review; Anatomy; mirror symmetry; mirror neuron; sensory-motor; Neocortex; Cerebral Cortex; Agnosia; aphasia; topographic map; multimodal; Association Learning/physiology}, Mesh = {Agnosia; Animals; Brain; Humans}, Month = {Jun}, Number = {2}, Pages = {237-94}, pmid = {5318481}, Pst = {ppublish}, Title = {Disconnexion syndromes in animals and man. I}, Volume = {88}, Year = {1965}, url = {papers/Geschwind_Brain1965.pdf}} @article{Rizzolatti:2001, Abstract = {The cortical motor system of primates is formed by a mosaic of anatomically and functionally distinct areas. These areas are not only involved in motor functions, but also play a role in functions formerly attributed to higher order associative cortical areas. In the present review, we discuss three types of higher functions carried out by the motor cortical areas: sensory-motor transformations, action understanding, and decision processing regarding action execution. We submit that generating internal representations of actions is central to cortical motor function. External contingencies and motivational factors determine then whether these action representations are transformed into actual actions.}, Author = {Rizzolatti, G and Luppino, G}, Date-Added = {2012-08-27 15:49:14 +0000}, Date-Modified = {2012-08-27 15:50:09 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {mirror neuron; mirror symmetry; Social Behavior; monkey; connectivity; Cognitive neuroscience; autism; Autistic Disorder; Attention; sensory-motor; multimodal; review; Neurophysiology; extracellular; Motor Cortex; Motor Neurons; sensory map; topographic map; Anatomy;}, Mesh = {Animals; Brain Mapping; Concept Formation; Decision Making; GABA Agonists; Hand; Hand Strength; Haplorhini; Higher Nervous Activity; Humans; Imitative Behavior; Models, Neurological; Motor Activity; Motor Cortex; Muscimol; Neural Pathways; Neurons; Observation; Parietal Lobe; Pattern Recognition, Visual; Psychomotor Performance; Sensation}, Month = {Sep}, Number = {6}, Pages = {889-901}, pmid = {11580891}, Pst = {ppublish}, Title = {The cortical motor system}, Volume = {31}, Year = {2001}, url = {papers/Rizzolatti_Neuron2001.pdf}} @article{Rizzolatti:2004, Abstract = {A category of stimuli of great importance for primates, humans in particular, is that formed by actions done by other individuals. If we want to survive, we must understand the actions of others. Furthermore, without action understanding, social organization is impossible. In the case of humans, there is another faculty that depends on the observation of others' actions: imitation learning. Unlike most species, we are able to learn by imitation, and this faculty is at the basis of human culture. In this review we present data on a neurophysiological mechanism--the mirror-neuron mechanism--that appears to play a fundamental role in both action understanding and imitation. We describe first the functional properties of mirror neurons in monkeys. We review next the characteristics of the mirror-neuron system in humans. We stress, in particular, those properties specific to the human mirror-neuron system that might explain the human capacity to learn by imitation. We conclude by discussing the relationship between the mirror-neuron system and language.}, Author = {Rizzolatti, Giacomo and Craighero, Laila}, Date-Added = {2012-08-27 15:45:54 +0000}, Date-Modified = {2012-08-27 15:48:06 +0000}, Doi = {10.1146/annurev.neuro.27.070203.144230}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {mirror neuron; mirror symmetry; Social Behavior; monkey; connectivity; Cognitive neuroscience; autism; Autistic Disorder; Attention; sensory-motor; multimodal; review; Neurophysiology; extracellular}, Mesh = {Animals; Dogs; Haplorhini; Humans; Imitative Behavior; Learning; Motor Cortex; Nerve Net; Neurons; Psychomotor Performance; Social Behavior; Verbal Behavior}, Pages = {169-92}, pmid = {15217330}, Pst = {ppublish}, Title = {The mirror-neuron system}, Volume = {27}, Year = {2004}, url = {papers/Rizzolatti_AnnuRevNeurosci2004.pdf}} @article{Bullmore:1997, Abstract = {Two separate theories that attempt to explain different aspects of schizophrenia have recently attracted much attention. The first, the neurodevelopmental hypothesis, postulates that deviations in early development establish a neuronal phenotype that predisposes to, or, in some versions, determines the later onset of schizophrenia. The second theory proposes that schizophrenic symptoms arise from abnormalities in neuronal connectivity. Here, we suggest that the findings from these two separate lines of inquiry can be integrated into a unitary framework: the dysplastic net hypothesis. In essence, this proposes that anatomical and physiological dysconnectivity of the adult schizophrenic brain is determined by dysplastic fetal brain development. We also indicate how abnormal connectivity between brain regions constituting large-scale neurocognitive networks is expressed in both the prepsychotic and psychotic phases of schizophrenia, and we examine possible risk factors (genetic and environmental) for dysplastic formation of these networks.}, Author = {Bullmore, E T and Frangou, S and Murray, R M}, Date-Added = {2012-08-27 15:08:13 +0000}, Date-Modified = {2012-08-27 15:09:35 +0000}, Journal = {Schizophr Res}, Journal-Full = {Schizophrenia research}, Keywords = {neurological disorder; Cognitive neuroscience; development; review; Schizophrenia; connectivity; dysplasia; cortical malformation; Neocortex}, Mesh = {Adult; Brain; Cognition Disorders; Disease Progression; Humans; Models, Neurological; Nerve Net; Schizophrenia}, Month = {Dec}, Number = {2-3}, Pages = {143-56}, pmid = {9468349}, Pst = {ppublish}, Title = {The dysplastic net hypothesis: an integration of developmental and dysconnectivity theories of schizophrenia}, Volume = {28}, Year = {1997}, url = {papers/Bullmore_SchizophrRes1997.pdf}} @article{Iacoboni:2006, Abstract = {The discovery of premotor and parietal cells known as mirror neurons in the macaque brain that fire not only when the animal is in action, but also when it observes others carrying out the same actions provides a plausible neurophysiological mechanism for a variety of important social behaviours, from imitation to empathy. Recent data also show that dysfunction of the mirror neuron system in humans might be a core deficit in autism, a socially isolating condition. Here, we review the neurophysiology of the mirror neuron system and its role in social cognition and discuss the clinical implications of mirror neuron dysfunction.}, Author = {Iacoboni, Marco and Dapretto, Mirella}, Date-Added = {2012-08-27 14:11:49 +0000}, Date-Modified = {2012-08-27 14:13:00 +0000}, Doi = {10.1038/nrn2024}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {autism; Autistic Disorder; mirror neuron; mirror symmetry; neurological disorder; monkey; human; Cognitive neuroscience; Neurophysiology; review}, Mesh = {Animals; Autistic Disorder; Cerebral Cortex; Empathy; Humans; Imitative Behavior; Neural Pathways; Neurons; Psychomotor Performance; Social Behavior; Social Behavior Disorders}, Month = {Dec}, Number = {12}, Pages = {942-51}, pmid = {17115076}, Pst = {ppublish}, Title = {The mirror neuron system and the consequences of its dysfunction}, Volume = {7}, Year = {2006}, url = {papers/Iacoboni_NatRevNeurosci2006.pdf}} @article{Williams:2008, Abstract = {Mirror neuron system dysfunction may underlie a self-other matching impairment, which has previously been suggested to account for autism. Embodied Cognition Theory, which proposes that action provides a foundation for cognition has lent further credence to these ideas. The hypotheses of a self-other matching deficit and impaired mirror neuron function in autism have now been well supported by studies employing a range of methodologies. However, underlying mechanisms require further exploration to explain how mirror neurons may be involved in attentional and mentalizing processes. Impairments in self-other matching and mirror neuron function are not necessarily inextricably linked and it seems possible that different sub-populations of mirror neurons, located in several regions, contribute differentially to social cognitive functions. It is hypothesized that mirror neuron coding for action-direction may be required for developing attentional sensitivity to self-directed actions, and consequently for person-oriented, stimulus-driven attention. Mirror neuron networks may vary for different types of social learning such as "automatic" imitation and imitation learning. Imitation learning may be more reliant on self-other comparison processes (based on mirror neurons) that identify differences as well as similarities between actions. Differential connectivity with the amygdala-orbitofrontal system may also be important. This could have implications for developing "theory of mind," with intentional self-other comparison being relevant to meta-representational abilities, and "automatic" imitation being more relevant to empathy. While it seems clear that autism is associated with impaired development of embodied aspects of cognition, the ways that mirror neurons contribute to these brain-behavior links are likely to be complex.}, Author = {Williams, Justin H G}, Date-Added = {2012-08-27 13:49:15 +0000}, Date-Modified = {2012-08-27 13:50:44 +0000}, Doi = {10.1002/aur.15}, Journal = {Autism Res}, Journal-Full = {Autism research : official journal of the International Society for Autism Research}, Keywords = {autism; Autistic Disorder; neurological disorder; human; mirror neuron; mirror symmetry; Cognitive neuroscience;}, Mesh = {Affect; Asperger Syndrome; Attention; Autistic Disorder; Brain; Child; Cognition Disorders; Fixation, Ocular; Frontal Lobe; Humans; Imitative Behavior; Interpersonal Relations; Magnetic Resonance Imaging; Neurons; Parietal Lobe; Personality Development; Psychomotor Performance; Self Concept; Social Behavior}, Month = {Apr}, Number = {2}, Pages = {73-90}, pmid = {19360654}, Pst = {ppublish}, Title = {Self-other relations in social development and autism: multiple roles for mirror neurons and other brain bases}, Volume = {1}, Year = {2008}, url = {papers/Williams_AutismRes2008.pdf}} @article{Murias:2007, Abstract = {BACKGROUND: Theoretical conceptions of autism spectrum disorder (ASD) and experimental studies of cerebral blood flow suggest abnormalities in connections among distributed neural systems in ASD. METHODS: Functional connectivity was assessed with electroencephalographic coherence between pairs of electrodes in a high-density electrode array in narrow frequency bands among 18 adults with ASD and 18 control adults in an eyes closed resting state. RESULTS: In the theta (3-6 Hz) frequency range, locally elevated coherence was evident for the ASD group, especially within left hemisphere frontal and temporal regions. In the lower alpha range (8-10 Hz), globally reduced coherence was evident for the ASD group within frontal regions and between frontal and all other scalp regions. The ASD group exhibited significantly greater relative power between 3 and 6 Hz and 13-17 Hz and significantly less relative power between 9 and 10 Hz. CONCLUSIONS: Robust patterns of over- and under-connectivity are apparent at distinct spatial and temporal scales in ASD subjects in the eyes closed resting state.}, Author = {Murias, Michael and Webb, Sara J and Greenson, Jessica and Dawson, Geraldine}, Date-Added = {2012-08-24 22:25:21 +0000}, Date-Modified = {2012-08-24 22:27:16 +0000}, Doi = {10.1016/j.biopsych.2006.11.012}, Journal = {Biol Psychiatry}, Journal-Full = {Biological psychiatry}, Keywords = {autism; Autistic Disorder; default mode network; resting state; Neurophysiology; human; Electroencephalography; EEG; neuroimaging; function; connectivity; Neocortex; cingulate; retrosplenial cortex}, Mesh = {Adolescent; Adult; Arousal; Autistic Disorder; Brain Mapping; Case-Control Studies; Cerebral Cortex; Cortical Synchronization; Electroencephalography; Humans; Male; Neural Pathways; Reference Values}, Month = {Aug}, Number = {3}, Pages = {270-3}, Pmc = {PMC2001237}, pmid = {17336944}, Pst = {ppublish}, Title = {Resting state cortical connectivity reflected in EEG coherence in individuals with autism}, Volume = {62}, Year = {2007}, url = {papers/Murias_BiolPsychiatry2007.pdf}} @article{Maestrini:2000, Author = {Maestrini, E and Paul, A and Monaco, A P and Bailey, A}, Date-Added = {2012-08-24 22:22:36 +0000}, Date-Modified = {2012-08-24 22:23:26 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Autistic Disorder; autism; Grants; review; gene; human; neurological disorder; Genetic Markers}, Mesh = {Autistic Disorder; Chromosome Aberrations; Chromosome Disorders; Chromosome Mapping; Chromosomes, Human; Female; Genetic Linkage; Genetic Testing; Genomic Library; Humans; Likelihood Functions; Lod Score; Male; Microsatellite Repeats; Polymorphism, Genetic}, Month = {Oct}, Number = {1}, Pages = {19-24}, pmid = {11086979}, Pst = {ppublish}, Title = {Identifying autism susceptibility genes}, Volume = {28}, Year = {2000}, url = {papers/Maestrini_Neuron2000.pdf}} @article{McCarthy:2004, Author = {McCarthy, Alice A}, Date-Added = {2012-08-24 22:21:25 +0000}, Date-Modified = {2012-08-24 22:22:08 +0000}, Doi = {10.1016/j.chembiol.2004.10.001}, Journal = {Chem Biol}, Journal-Full = {Chemistry \& biology}, Keywords = {Autistic Disorder; autism; neurological disorder; human; gene; Grants; review}, Mesh = {Autistic Disorder; Child; Genetic Predisposition to Disease; Humans}, Month = {Oct}, Number = {10}, Pages = {1325-6}, pmid = {15489156}, Pst = {ppublish}, Title = {The genetics of autism}, Volume = {11}, Year = {2004}, url = {papers/McCarthy_ChemBiol2004.pdf}} @article{White:1986, Abstract = {The structure and connectivity of the nervous system of the nematode Caenorhabditis elegans has been deduced from reconstructions of electron micrographs of serial sections. The hermaphrodite nervous system has a total complement of 302 neurons, which are arranged in an essentially invariant structure. Neurons with similar morphologies and connectivities have been grouped together into classes; there are 118 such classes. Neurons have simple morphologies with few, if any, branches. Processes from neurons run in defined positions within bundles of parallel processes, synaptic connections being made en passant. Process bundles are arranged longitudinally and circumferentially and are often adjacent to ridges of hypodermis. Neurons are generally highly locally connected, making synaptic connections with many of their neighbours. Muscle cells have arms that run out to process bundles containing motoneuron axons. Here they receive their synaptic input in defined regions along the surface of the bundles, where motoneuron axons reside. Most of the morphologically identifiable synaptic connections in a typical animal are described. These consist of about 5000 chemical synapses, 2000 neuromuscular junctions and 600 gap junctions.}, Author = {White, J G and Southgate, E and Thomson, J N and Brenner, S}, Date-Added = {2012-08-24 21:47:07 +0000}, Date-Modified = {2012-08-24 21:48:53 +0000}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {connectivity; connectome; Caenorhabditis elegans; neuroinformatics}, Month = {Nov}, Number = {1165}, Pages = {1-340}, pmid = {22462104}, Pst = {ppublish}, Title = {The structure of the nervous system of the nematode Caenorhabditis elegans}, Volume = {314}, Year = {1986}, url = {papers/White_PhilosTransRSocLondBBiolSci1986.pdf}} @article{Frith:2001, Abstract = {Experimental evidence shows that the inability to attribute mental states, such as desires and beliefs, to self and others (mentalizing) explains the social and communication impairments of individuals with autism. Brain imaging studies in normal volunteers highlight a circumscribed network that is active during mentalizing and links medial prefrontal regions with posterior superior temporal sulcus and temporal poles. The brain abnormality that results in mentalizing failure in autism may involve weak connections between components of this system.}, Author = {Frith, U}, Date-Added = {2012-08-24 17:01:30 +0000}, Date-Modified = {2012-08-24 17:02:21 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Grants; Autistic Disorder; neurological disorder; human; wholeBrain}, Mesh = {Autistic Disorder; Brain; Cognition Disorders; Humans}, Month = {Dec}, Number = {6}, Pages = {969-79}, pmid = {11754830}, Pst = {ppublish}, Title = {Mind blindness and the brain in autism}, Volume = {32}, Year = {2001}, url = {papers/Frith_Neuron2001.pdf}} @article{Alivisatos:2012, Abstract = {The function of neural circuits is an emergent property that arises from the coordinated activity of large numbers of neurons. To capture this, we propose launching a large-scale, international public effort, the Brain Activity Map Project, aimed at reconstructing the full record of neural activity across complete neural circuits. This technological challenge could prove to be an invaluable step toward understanding fundamental and pathological brain processes.}, Author = {Alivisatos, A Paul and Chun, Miyoung and Church, George M and Greenspan, Ralph J and Roukes, Michael L and Yuste, Rafael}, Date-Added = {2012-08-23 17:17:02 +0000}, Date-Modified = {2012-08-23 17:18:14 +0000}, Doi = {10.1016/j.neuron.2012.06.006}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {next; Spontaneous activity; development; Neocortex; cortex; whole brain; wholeBrain; review; Neurophysiology; calcium imaging; connectivity; connectome; graph theory; ideas}, Month = {Jun}, Number = {6}, Pages = {970-4}, pmid = {22726828}, Pst = {ppublish}, Title = {The brain activity map project and the challenge of functional connectomics}, Volume = {74}, Year = {2012}, url = {papers/Alivisatos_Neuron2012.pdf}} @article{Bulankina:2012, Abstract = {The organ of Corti, the sensory epithelium of the mammalian auditory system, uses afferent and efferent synapses for encoding auditory signals and top-down modulation of cochlear function. During development, the final precisely ordered sensorineural circuit is established following excessive formation of afferent and efferent synapses and subsequent refinement. Here, we review the development of innervation of the mouse organ of Corti and its regulation.}, Author = {Bulankina, A V and Moser, T}, Date-Added = {2012-08-16 21:46:09 +0000}, Date-Modified = {2012-08-16 22:13:44 +0000}, Doi = {10.1152/physiol.00036.2011}, Journal = {Physiology (Bethesda)}, Journal-Full = {Physiology (Bethesda, Md.)}, Keywords = {Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; topographic map; Auditory Cortex; Auditory Pathways; Cochlear Nerve; Cochlea/innervation/physiology; development; review; grants; next}, Mesh = {Animals; Cell Differentiation; Cochlea; Hair Cells, Auditory; Humans; Mice; Neurons, Efferent; Synapses}, Month = {Apr}, Number = {2}, Pages = {100-12}, pmid = {22505666}, Pst = {ppublish}, Title = {Neural circuit development in the mammalian cochlea}, Volume = {27}, Year = {2012}, url = {papers/Bulankina_Physiology(Bethesda)2012.pdf}} @article{Fair:2008, Abstract = {In recent years, the brain's "default network," a set of regions characterized by decreased neural activity during goal-oriented tasks, has generated a significant amount of interest, as well as controversy. Much of the discussion has focused on the relationship of these regions to a "default mode" of brain function. In early studies, investigators suggested that, the brain's default mode supports "self-referential" or "introspective" mental activity. Subsequently, regions of the default network have been more specifically related to the "internal narrative," the "autobiographical self," "stimulus independent thought," "mentalizing," and most recently "self-projection." However, the extant literature on the function of the default network is limited to adults, i.e., after the system has reached maturity. We hypothesized that further insight into the network's functioning could be achieved by characterizing its development. In the current study, we used resting-state functional connectivity MRI (rs-fcMRI) to characterize the development of the brain's default network. We found that the default regions are only sparsely functionally connected at early school age (7-9 years old); over development, these regions integrate into a cohesive, interconnected network.}, Author = {Fair, Damien A and Cohen, Alexander L and Dosenbach, Nico U F and Church, Jessica A and Miezin, Francis M and Barch, Deanna M and Raichle, Marcus E and Petersen, Steven E and Schlaggar, Bradley L}, Date-Added = {2012-08-16 21:39:42 +0000}, Date-Modified = {2012-08-16 21:44:18 +0000}, Doi = {10.1073/pnas.0800376105}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {fMRI; development; human; Spontaneous activity; Attention; conciousness; network; graph theory; Theoretical; Adolescence; 21 Activity-development; Grants; mirror symmetry; wholeBrain; whole brain; next}, Mesh = {Adolescent; Adult; Brain; Brain Mapping; Child; Humans; Magnetic Resonance Imaging; Nerve Net}, Month = {Mar}, Number = {10}, Pages = {4028-32}, Pmc = {PMC2268790}, pmid = {18322013}, Pst = {ppublish}, Title = {The maturing architecture of the brain's default network}, Volume = {105}, Year = {2008}, url = {papers/Fair_ProcNatlAcadSciUSA2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0800376105}} @article{Wijetunge:2008, Abstract = {We have previously reported that mGluR5 signaling via PLC-beta1 regulates the development of whisker patterns within S1 (barrel) cortex of mice (Hannan et al., 2001). However, whether these defects arise from the loss of postsynaptic mGluR5 signaling, and whether the level of mGluR5 is important for barrel formation, was not examined. Furthermore, whether mGluR5 regulates other developmental processes that occur before or after barrel development is not known. We now show that mGluR5 is present postsynaptically at thalamocortical synapses during barrel formation. In addition, Mglur5(+/-) mice exhibit normal TCA patch formation but reduced cellular segregation in layer 4, indicating a dose-dependent role for mGluR5 in the regulation of pattern formation. Furthermore Mglur5(-/-) and Mglur5(+/-) mice display normal cortical arealization, layer formation, and size of PMBSF indicating the defects within S1 do not result from general abnormalities of cortical mapping during earlier stages of development. At P21 layer 4 neurons from Mglur5(-/-) and Mglur5(+/-) mice show a significant reduction in spine density but normal dendritic complexity compared with Mglur5(+/+) mice indicating a role in synaptogenesis during cortical development. Finally, mGluR5 regulates pattern formation throughout the trigeminal system of mice as the representation of the AS whiskers in the PrV, VpM, and S1 cortex was disrupted in Mglur5(-/-) mice. Together these data indicate a key role for mGluR5 at both early and late stages of neuronal development in the trigeminal system of mice.}, Author = {Wijetunge, Lasani S and Till, Sally M and Gillingwater, Thomas H and Ingham, Cali A and Kind, Peter C}, Date-Added = {2012-08-16 21:28:45 +0000}, Date-Modified = {2012-08-16 21:30:43 +0000}, Doi = {10.1523/JNEUROSCI.2600-08.2008}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Structure-Activity Relationship; development; Somatosensory Cortex; Neocortex; Thalamus; 21 Activity-development; Mouse; gene; Transgenes; mutant; Technique; topographic map; grants}, Mesh = {Afferent Pathways; Animals; Dendritic Spines; Female; Glutamic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Nervous System Malformations; Neural Pathways; Neurogenesis; Receptors, Metabotropic Glutamate; Somatosensory Cortex; Synapses; Synaptic Transmission; Trigeminal Nerve; Ventral Thalamic Nuclei; Vibrissae}, Month = {Dec}, Number = {49}, Pages = {13028-37}, pmid = {19052194}, Pst = {ppublish}, Title = {mGluR5 regulates glutamate-dependent development of the mouse somatosensory cortex}, Volume = {28}, Year = {2008}, url = {papers/Wijetunge_JNeurosci2008.pdf}} @article{Issa:1999, Abstract = {Microelectrode recordings and optical imaging of intrinsic signals were used to define the critical period for susceptibility to monocular deprivation (MD) in the primary visual cortex of the ferret. Ferrets were monocularly deprived for 2, 7 or >14 d, beginning between postnatal day 19 (P19) and P110. The responses of visual cortical neurons to stimulation of the two eyes were used to gauge the onset, peak, and decline of the critical period. MDs ending before P32 produced little or no loss of response to the deprived eye. MDs of 7 d or more beginning around P42 produced the greatest effects. A rapid decline in cortical susceptibility to MD was observed after the seventh week of life, such that MDs beginning between P50 and P65 were approximately half as effective as those beginning on P42; MDs beginning after P100 did not reduce the response to the deprived eye below that to the nondeprived eye. At all ages, 2 d deprivations were 55-85% as effective as 7 d of MD. Maps of intrinsic optical responses from the deprived eye were weaker and less well tuned for orientation than those from the nondeprived eye, with the weakest maps seen in the hemisphere ipsilateral to the deprived eye. Analysis of the effects of 7 d and longer deprivations revealed a second period of plasticity in cortical responses in which MD induced an effect like that of strabismus. After P70, MD caused a marked loss of binocular responses with little or no overall loss of response to the deprived eye. The critical period measured here is compared to other features of development in ferret and cat.}, Author = {Issa, N P and Trachtenberg, J T and Chapman, B and Zahs, K R and Stryker, M P}, Date-Added = {2012-08-16 21:03:02 +0000}, Date-Modified = {2012-08-16 21:07:02 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {ferret; visual system; visual cortex; Sensory Deprivation; Critical Period; plasticity; structural remodeling; Structure-Activity Relationship; synapse formation; optical imaging; Neurophysiology; retinal wave paper; Spontaneous activity; review}, Mesh = {Aging; Animals; Critical Period (Psychology); Dominance, Cerebral; Ferrets; Functional Laterality; Neuronal Plasticity; Ocular Physiological Phenomena; Sensory Deprivation; Vision, Monocular; Visual Cortex}, Month = {Aug}, Number = {16}, Pages = {6965-78}, Pmc = {PMC2413141}, pmid = {10436053}, Pst = {ppublish}, Title = {The critical period for ocular dominance plasticity in the Ferret's visual cortex}, Volume = {19}, Year = {1999}, url = {papers/Issa_JNeurosci1999.pdf}} @article{Coogan:1996, Abstract = {We have investigated the development of intrinsic and interareal connections in areas V1 and V2 of the macaque monkey using postmortem transport of the lipophilic fluorescent tracer diI, applied to brains fixed at different pre- and postnatal ages. Intrinsic connections in the deep layers of V1 are evident on embryonic day 108 (E108), but are not robust in the superficial layers until around E118, when migration is largely complete. Both intrinsic horizontal projections and extrinsic projections to V2 initially have a continuous distribution. Patchy projections are first evident in V1 around E145, the same age at which cytochrome oxidase blobs appear, presumably signaling the differentiation of the blob-dominated and interblob-dominated streams in the primary visual cortex. The magnocellular-dominated stream becomes distinct at earlier stages (by E122), as judged by connectional and histochemical criteria. In area V2, intrinsic connections initially (at E108) involve only deep layer cells and do not have a clustered organization. By E130, superficial layer cells are involved and the V2 intrinsic connections have a patchy distribution; by E145, an adult-like pattern is present. The projection from V2 to V1 passes through an early stage (up to E133) of originating principally from deep layer cells, and thereafter originating from superficial as well as deep layers. We found evidence for changes in dendritic morphology during development. Most notably, at E118, many neurons in layer 6 which are involved in intrinsic or interareal connections have dendrites that extend well into the superficial layers, even into layer 1, a characteristic not reported in the adult.}, Author = {Coogan, T A and Van Essen, D C}, Date-Added = {2012-07-16 17:26:13 +0000}, Date-Modified = {2012-07-16 17:26:13 +0000}, Doi = {10.1002/(SICI)1096-9861(19960826)372:3\<327::AID-CNE1\>3.0.CO;2-4}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Mesh = {Animals; Animals, Newborn; Cerebral Cortex; Histocytochemistry; Macaca mulatta; Neural Pathways}, Month = {Aug}, Number = {3}, Pages = {327-42}, pmid = {8873864}, Pst = {ppublish}, Title = {Development of connections within and between areas V1 and V2 of macaque monkeys}, Volume = {372}, Year = {1996}, url = {papers/Coogan_JCompNeurol1996.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1096-9861(19960826)372:3%5C<327::AID-CNE1%5C>3.0.CO;2-4}} @article{Furukawa:1997, Abstract = {Development of the vertebrate eye has been found to require the activity of several genes encoding homeodomain proteins (Freund, C., Horsford, D. J. & McInnes, R. R. (1996) Hum. Mol. Genet. 5, 1471-1488). Some of these genes, or portions thereof, are highly conserved across phyla. In this paper, we report the identification of a novel homeobox gene, rax (retina and anterior neural fold homeobox), whose expression pattern suggests an important role in eye development. The predicted amino acid sequence of Rax comprises a protein with a paired-type homeobox, as well as the octapeptide that is found in many paired-type homeobox genes. In addition, in the C terminus of Rax, we found a 15-aa domain that we have named the OAR domain. This domain is also found in several other homeobox genes. In the early mouse embryo, rax is expressed in the anterior neural fold, including areas that will give rise to the ventral forebrain and optic vesicles. Once the optic vesicles form, rax expression is restricted to the ventral diencephalon and the optic vesicles. At later stages, rax expression is found only in the developing retina. After birth, the expression of rax is restricted to the zone of proliferating cells within the retina, and expression gradually decreases as proliferation declines. These findings suggest that rax is one of the molecules that define the eye field during early development and that it has a role in the proliferation and/or differentiation of retinal cells.}, Author = {Furukawa, T and Kozak, C A and Cepko, C L}, Date-Added = {2012-07-14 13:56:05 +0000}, Date-Modified = {2012-07-14 13:56:53 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {retina; development; mouse; gene; Transcription; Embryo and Fetal Development; eye; visual system}, Mesh = {Amino Acid Sequence; Animals; Base Sequence; Chromosome Mapping; DNA, Complementary; Eye Proteins; Gene Expression Regulation, Developmental; Genes, Homeobox; Homeodomain Proteins; Mice; Molecular Sequence Data; Nervous System; RNA, Messenger; Retina; Sequence Homology, Amino Acid; Transcription Factors}, Month = {Apr}, Number = {7}, Pages = {3088-93}, Pmc = {PMC20326}, pmid = {9096350}, Pst = {ppublish}, Title = {rax, a novel paired-type homeobox gene, shows expression in the anterior neural fold and developing retina}, Volume = {94}, Year = {1997}, url = {papers/Furukawa_ProcNatlAcadSciUSA1997.pdf}} @article{Swindell:2006, Abstract = {Rx is a homeobox-containing gene that is critical for vertebrate eye development. Its expression domain delineates a field of cells from which the retina and the ventral hypothalamus develop. The 5' upstream regulatory sequences of the medaka fish Rx gene are functionally conserved during evolution to a degree that they direct gene expression into the Rx-expressing field of cells in mice. Using these sequences, we made a Cre line that can be used for inactivation of gene expression in the developing retina.}, Author = {Swindell, Eric C and Bailey, Travis J and Loosli, Felix and Liu, Chaomei and Amaya-Manzanares, Felipe and Mahon, Kathleen A and Wittbrodt, Joachim and Jamrich, Milan}, Date-Added = {2012-07-14 13:37:35 +0000}, Date-Modified = {2012-07-14 13:38:16 +0000}, Doi = {10.1002/dvg.20225}, Journal = {Genesis}, Journal-Full = {Genesis (New York, N.Y. : 2000)}, Keywords = {gene; mouse; Technique; retina; visual system; Neocortex; development; Transcription}, Mesh = {Alleles; Animals; Eye Proteins; Gene Expression Regulation, Developmental; Genes, Homeobox; Genes, Reporter; Green Fluorescent Proteins; Homeodomain Proteins; Integrases; Lac Operon; Mice; Mice, Transgenic; Oryzias; Retina}, Month = {Aug}, Number = {8}, Pages = {361-3}, pmid = {16850473}, Pst = {ppublish}, Title = {Rx-Cre, a tool for inactivation of gene expression in the developing retina}, Volume = {44}, Year = {2006}, url = {papers/Swindell_Genesis2006.pdf}} @article{Olney:1968a, Author = {Olney, J W}, Date-Added = {2012-07-10 16:25:27 +0000}, Date-Modified = {2012-07-10 16:26:20 +0000}, Journal = {Invest Ophthalmol}, Journal-Full = {Investigative ophthalmology}, Keywords = {histology; connectivity; development; 21 Activity-development; Structure-Activity Relationship; structural remodeling; mouse; visual cortex; synapses; synapse formation; electron microscopy; retina; visual system}, Mesh = {Animals; Electroretinography; Mice; Microscopy, Electron; Photoreceptor Cells; Retina; Synapses}, Month = {Jun}, Number = {3}, Pages = {250-68}, pmid = {5655873}, Pst = {ppublish}, Title = {An electron microscopic study of synapse formation, receptor outer segment development, and other aspects of developing mouse retina}, Volume = {7}, Year = {1968}, url = {papers/Olney_InvestOphthalmol1968.pdf}} @article{Olney:1968, Author = {Olney, J W}, Date-Added = {2012-07-10 16:25:25 +0000}, Date-Modified = {2012-07-10 16:26:25 +0000}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {histology; connectivity; development; 21 Activity-development; Structure-Activity Relationship; structural remodeling; mouse; visual cortex; synapses; synapse formation; electron microscopy; retina; visual system}, Mesh = {Animals; Electrophysiology; Histological Techniques; Mice; Microscopy, Electron; Retina; Sensory Receptor Cells; Synapses}, Month = {Apr}, Number = {5138}, Pages = {281-2}, pmid = {4869714}, Pst = {ppublish}, Title = {Centripetal sequence of appearance of receptor-bipolar synaptic structures in developing mouse retina}, Volume = {218}, Year = {1968}} @article{Cragg:1975, Abstract = {Synapses have been counted by electron microscopy and neurones by light microscopy through the depth of the visual cortex in a series of cats from 37 days gestation to adulthood. A few definite synapses are present as early as three weeks before birth, but there is then a latent period of four weeks before synapses increase rapidly in number 8-37 days after birth. The synapses occur just above and just below the cell plate at first, but in the adult cat they become evenly distributed in the depth of the cortex. The gradual separation of neurones by neuropil during development precedes a parallel increase in the density of synapses by about one week. The average number of synapses associated with one neurone rises to a peak of about 13,000 at seven weeks after birth. The densities of synapses and of neurones subsequently fall to slightly lower values in adult cats as the glial cells continue to develop. The timing of synaptic development in the visual cortex has been compared quantitatively with that in the L. G. N. and qualitatively with synaptogenesis in the retina. Synapses develop in the L. G. N. and cortex in a parallel fashion, and the L. G. N. precedes the cortex by a short interval of about two days. In the cell plate of the retina a few receptor synapses are present nine days before birth. Inner plexiform synapses are aslo present at this time, but ribbon-containing synapses do not appear until birth. Very few receptors possess outer segments with discs at birth, but five days later disc-bearing outer segments have developed. Thus synaptic development starts before afferent impulses can enter the visual system, but the main increase in synapses in the L. G. N. and cortex takes place four weeks after the start of synapse formation while the visual system is being used.}, Author = {Cragg, B G}, Date-Added = {2012-07-10 16:21:06 +0000}, Date-Modified = {2012-07-10 16:21:59 +0000}, Doi = {10.1002/cne.901600202}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {histology; connectivity; development; 21 Activity-development; Structure-Activity Relationship; structural remodeling; cat; visual cortex; synapses; synapse formation; electron microscopy; LGN}, Mesh = {Age Factors; Aging; Animals; Cats; Cell Count; Geniculate Bodies; Gestational Age; Microscopy, Electron; Neural Pathways; Retina; Synapses; Visual Cortex}, Month = {Mar}, Number = {2}, Pages = {147-66}, pmid = {1112924}, Pst = {ppublish}, Title = {The development of synapses in the visual system of the cat}, Volume = {160}, Year = {1975}, url = {papers/Cragg_JCompNeurol1975.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901600202}} @article{Mathers:1978, Abstract = {The development of synapses in the visual cortex (VC) and superior colliculus (SC) of the rabbit has been examined with the electron microscope. In both areas, the number of synapses reaches adult levels by 20--25 days of postnatal age, but the development in the visual cortex is delayed in comparison to that in the superior colliculus. When S synapses (spheroidal vesicles, asymmetric thickening) are compared with F synapses (flattened vesicles, symmetric thickening), even greater differences are seen. In both the VC and SC, S synapses develop earlier than F synapses, though there is considerable overlap. Of interest is that fact that synapses in the visual cortex seem to overshoot their adult levels late in development, suggesting that an excess of synapses may be formed in this system. Multiple synapses, probably of retinal origin, increase in the first 3 weeks of synaptic development in the SC, but never are present in significant proportions in the VC. Synapse formation most often is characterized by formation of a junction and a postsynaptic thickening, followed by acquisition of synaptic vesicles. After 15 days, there is only a small number of such "non-vesicle synapses" in either the SC or VC.}, Author = {Mathers, Jr, L H and Mercer, K L and Marshall, P E}, Date-Added = {2012-07-10 16:18:54 +0000}, Date-Modified = {2012-07-10 16:19:49 +0000}, Journal = {Exp Brain Res}, Journal-Full = {Experimental brain research. Experimentelle Hirnforschung. Exp{\'e}rimentation c{\'e}r{\'e}brale}, Keywords = {histology; connectivity; development; 21 Activity-development; Structure-Activity Relationship; structural remodeling; Rabbits; visual cortex; synapses; synapse formation; electron microscopy; Superior Colliculus; optic tectum}, Mesh = {Age Factors; Animals; Cell Count; Cell Differentiation; Dendrites; Rabbits; Retina; Superior Colliculi; Synapses; Synaptic Vesicles; Visual Cortex; Visual Pathways}, Month = {Nov}, Number = {3-4}, Pages = {353-69}, pmid = {729659}, Pst = {ppublish}, Title = {Synaptic development in the rabbit superior colliculus and visual cortex}, Volume = {33}, Year = {1978}, url = {papers/Mathers_ExpBrainRes1978.pdf}} @article{Blue:1983, Abstract = {We have examined quantitatively the formation and maturation of synapses in the visual cortex of the rat. The density of the total number of synapses (synapses per 100 micron2 neuropil) as well as the densities of Gray's type I and type II contacts were estimated from photographic montages of coronal strips of visual cortex from rats of various postnatal ages. Histograms of synaptic density as a function of depth were prepared, and the mean values of the postsynaptic density length and vesicle number per terminal were estimated for the two synapse types at each age examined. During the first few days of life, synapses were concentrated in the subplate region. By the latter part of the second postnatal week they were present throughout the cortex and an adult-like distribution, in which the highest densities were present in the superficial layers, was achieved by day 14. The postsynaptic density length of the type I synapses remained relatively unchanged during development but that of the type II synapses was more variable. Specifically, it was significantly longer during the second and third postnatal weeks compared to earlier ages and to adult values. The mean number of vesicles per terminal for the two synapse types increased with age until day 28. Subsequently, it only increased slightly between days 28 and 90 for the type I synapses but decreased significantly for the type II synaptic contacts. At all ages examined, type I synapses formed the majority of synaptic contacts. The developmental pattern appeared to differ for the two synapse types. The density of type I synapses increased continuously during the first three weeks and achieved a mean value close to that of adult animals by day 20. In contrast, the density of type II synapses did not increase significantly until day 6, increased dramatically in the second and third postnatal weeks, and then declined markedly between days 20 and 90. The observed decrease in the density of type II synaptic contacts is a clear example of synapse elimination in the visual cortex.}, Author = {Blue, M E and Parnavelas, J G}, Date-Added = {2012-07-10 16:16:27 +0000}, Date-Modified = {2012-07-10 16:18:13 +0000}, Journal = {J Neurocytol}, Journal-Full = {Journal of neurocytology}, Keywords = {histology; connectivity; development; 21 Activity-development; Structure-Activity Relationship; structural remodeling; rat; visual cortex; synapses; synapse formation; electron microscopy}, Mesh = {Age Factors; Animals; Axons; Cell Differentiation; Dendrites; Rats; Social Environment; Synapses; Synaptic Vesicles; Visual Cortex}, Month = {Aug}, Number = {4}, Pages = {697-712}, pmid = {6619907}, Pst = {ppublish}, Title = {The formation and maturation of synapses in the visual cortex of the rat. II. Quantitative analysis}, Volume = {12}, Year = {1983}, url = {papers/Blue_JNeurocytol1983.pdf}} @article{Chapman:1993, Abstract = {The orientation selectivity of cells in ferret primary visual cortex was studied during normal development and in animals deprived of vision or of visual cortical activity. In normal animals from the age when visual responses were first recorded (postnatal day 23) through postnatal week 5, only about 25% of cells showed orientation-selective responses. By postnatal week 7, cortical responses had matured to an adult-like state, with approximately 75% of cells clearly selective for orientation. This development of orientation selectivity was not merely a reflection of the development of cortical cell responsiveness: at all ages studied, there was no correlation between responsiveness and selectivity. Infusion of TTX into visual cortex to silence neuronal activity completely blocked the maturation of orientation selectivity. Visual deprivation by bilateral lid suture impaired but did not completely block the normal development of orientation selectivity. We conclude that the maturation of orientation-selective responses in ferret primary visual cortex requires cortical neuronal activity, and that normal development requires visually driven activity.}, Author = {Chapman, B and Stryker, M P}, Date-Added = {2012-07-06 20:07:12 +0000}, Date-Modified = {2012-07-06 20:07:54 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; topographic map; visual system; Neocortex; Retinal Ganglion Cells; Tetrodotoxin; ferret; retinal wave paper; topographic map}, Mesh = {Animals; Animals, Newborn; Ferrets; Neurons; Sensory Deprivation; Tetrodotoxin; Visual Cortex; Visual Fields; Visual Perception}, Month = {Dec}, Number = {12}, Pages = {5251-62}, pmid = {8254372}, Pst = {ppublish}, Title = {Development of orientation selectivity in ferret visual cortex and effects of deprivation}, Volume = {13}, Year = {1993}} @article{Ruthazer:1996, Abstract = {Horizontal connections in area 17 of adult cats and ferrets link cells with similar preferred orientations by a patchy network of projections extending several millimeters across the cortex. The maturation of orientation selectivity in ferret area 17 has been demonstrated previously by quantitative single-unit recording and optical imaging to begin at approximately postnatal days (P) 32-P36. We therefore made restricted injections of cholera toxin B-subunit (CTB) or CTB-gold into ferret area 17 at a series of developmental ages and statistically quantified the degree of clustering in plots of retrogradely labeled cells in tangential sections through layer III for comparison to the published values for orientation tuning at each age. At P21, horizontal connections within area 17 lacked patchiness entirely, although clear patches of labeled cells were present in extrastriate areas. By P27, significant clustering of horizontal connections within area 17 was present. A second phase of cluster refinement was observed to occur at approximately P34-P36, coinciding with the emergence of mature orientation tuning and maps. Continuous silencing of cortical action potentials by chronic tetrodotoxin infusion from P21 resulted in a spatially random distribution of retrogradely labeled cells at P34. In contrast, bilateral enucleation from P21 did not prevent the initial development of clustered horizontal connections. We conclude, based on our findings and those of others, that the anatomical specificity of long-range horizontal connections results from an activity-dependent process that initially can use spontaneous activity in the cortical and thalamic networks to establish crude periodic connections and later uses visual cues to refine these connections.}, Author = {Ruthazer, E S and Stryker, M P}, Date-Added = {2012-07-06 20:05:08 +0000}, Date-Modified = {2012-07-06 20:06:48 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; topographic map; visual system; Neocortex; Retinal Ganglion Cells; Ferrets; connectivity}, Mesh = {Animals; Brain Mapping; Cats; Cell Count; Cholera Toxin; Ferrets; Gold; Neurons; Sensitivity and Specificity; Vision, Ocular; Visual Cortex; Visual Pathways}, Month = {Nov}, Number = {22}, Pages = {7253-69}, pmid = {8929433}, Pst = {ppublish}, Title = {The role of activity in the development of long-range horizontal connections in area 17 of the ferret}, Volume = {16}, Year = {1996}} @article{Sretavan:1988, Abstract = {The cellular mechanisms by which the axons of individual neurons achieve their precise terminal branching patterns are poorly understood. In the visual system of adult cats, retinal ganglion cell axons from each eye form narrow cylindrical terminal arborizations restricted to alternate non-overlapping layers within the lateral geniculate nucleus (LGN). During prenatal development, axon arborizations from the two eyes are initially simple in shape and are intermixed with each other; they then gradually segregate to form complex adult-like arborizations in separate eye-specific layers by birth. Here we report that ganglion cell axons exposed to tetrodotoxin (TTX) to block neuronal activity during fetal life fail to form the normal pattern of terminal arborization. Individual TTX-treated axon arborizations are not stunted in their growth, but instead produce abnormally widespread terminal arborizations which extend across the equivalent of approximately two eye-specific layers. These observations suggest that during fetal development of the central nervous system, the formation of morphologically appropriate and correctly located axon terminal arborizations within targets is brought about by an activity-dependent process.}, Author = {Sretavan, D W and Shatz, C J and Stryker, M P}, Date-Added = {2012-07-06 20:03:37 +0000}, Date-Modified = {2013-08-27 20:28:49 +0000}, Doi = {10.1038/336468a0}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; topographic map; visual system; Neocortex; Retinal Ganglion Cells; Tetrodotoxin; cat; retinal wave paper; currOpinRvw}, Mesh = {Animals; Axonal Transport; Axons; Cats; Female; Geniculate Bodies; Gestational Age; Maternal-Fetal Exchange; Pregnancy; Retina; Retinal Ganglion Cells; Tetrodotoxin}, Month = {Dec}, Number = {6198}, Pages = {468-71}, pmid = {2461517}, Pst = {ppublish}, Title = {Modification of retinal ganglion cell axon morphology by prenatal infusion of tetrodotoxin}, Volume = {336}, Year = {1988}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/336468a0}} @article{Shatz:1988, Abstract = {In the adult mammalian visual system, ganglion cell axons from the two eyes are segregated from each other into separate layers within their principal target, the lateral geniculate nucleus. The involvement of spontaneously generated action potential activity in the process of segregation was investigated during the fetal period in which segregation normally occurs in the cat, between embryonic day 45 (E45) and birth (E65). Tetrodotoxin, which blocks the voltage-sensitive sodium channel, was used to prevent action potentials. Fetuses received continuous intracranial infusions of tetrodotoxin from osmotic minipumps implanted in utero on E42. After a 2-week infusion, intraocular injections of anterograde tracers revealed that tetrodotoxin prevented segregation. The contralateral projection filled the lateral geniculate nucleus uniformly, and the ipsilateral projection expanded to occupy most of what would normally be contralaterally innervated layer A. Thus, in the fetus, long before the onset of vision, spontaneous action potential activity is likely to be present in the visual system and to contribute to the segregation of the retinogeniculate pathway.}, Author = {Shatz, C J and Stryker, M P}, Date-Added = {2012-07-06 20:02:05 +0000}, Date-Modified = {2013-08-27 20:30:15 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; topographic map; visual system; Neocortex; Retinal Ganglion Cells; Tetrodotoxin; cat; retinal wave paper; currOpinRvw}, Mesh = {Afferent Pathways; Animals; Cats; Female; Fetus; Infusions, Parenteral; Optic Chiasm; Pregnancy; Reference Values; Tetrodotoxin; Visual Pathways}, Month = {Oct}, Number = {4875}, Pages = {87-9}, pmid = {3175636}, Pst = {ppublish}, Title = {Prenatal tetrodotoxin infusion blocks segregation of retinogeniculate afferents}, Volume = {242}, Year = {1988}} @article{Demas:2003, Abstract = {In the immature retina, correlated spontaneous activity in the form of propagating waves is thought to be necessary for the refinement of connections between the retina and its targets. The continued presence of this activity in the mature retina would interfere with the transmission of information about the visual scene. The mechanisms responsible for the disappearance of retinal waves are not well understood, but one hypothesis is that visual experience is important. To test this hypothesis, we monitored the developmental changes in spontaneous retinal activity of both normal mice and mice reared in the dark. Using multi-electrode array recordings, we found that retinal waves in normally reared mice are present at postnatal day (P) 9 and begin to break down shortly after eye opening, around P15. By P21, waves have disappeared, and synchronous firing is comparable with that observed in the adult (6 weeks). In mice raised in the dark, we found a similar time course for the disappearance of waves. However, at P15, dark-reared retinas occasionally showed abnormally long periods of relative inactivity, not seen in controls. Apart from this quiescence, we found no striking differences between the patterns of spontaneous retinal activity from normal and dark-reared mice. We therefore suggest that visual experience is not required for the loss of synchronous spontaneous activity.}, Author = {Demas, Jay and Eglen, Stephen J and Wong, Rachel O L}, Date-Added = {2012-07-06 14:00:12 +0000}, Date-Modified = {2012-07-06 14:01:44 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity; retinal wave paper; 21 Activity-development; Structure-Activity Relationship; topographic map; Sensory/physiology; visual system; mouse; Neurophysiology; extracellular}, Mesh = {Action Potentials; Animals; Culture Techniques; Dark Adaptation; Kinetics; Mice; Mice, Inbred C57BL; Periodicity; Retina; Vision, Ocular}, Month = {Apr}, Number = {7}, Pages = {2851-60}, pmid = {12684472}, Pst = {ppublish}, Title = {Developmental loss of synchronous spontaneous activity in the mouse retina is independent of visual experience}, Volume = {23}, Year = {2003}, url = {papers/Demas_JNeurosci2003.pdf}} @article{Thivierge:2009, Abstract = {Highly non-random forms of spontaneous activity are proposed to play an instrumental role in the early development of the visual system. However, both the fundamental properties of spontaneous activity required to drive map formation, as well as the exact role of this information remain largely unknown. Here, a realistic computational model of spontaneous retinal waves is employed to demonstrate that both the amplitude and frequency of waves may play determining roles in retinocollicular map formation. Furthermore, results obtained with different learning rules show that spike precision in the order of milliseconds may be instrumental to neural development: a rule based on precise spike interactions (spike-timing-dependent plasticity) reduced the density of aberrant projections to the SC to a markedly greater extent than a rule based on interactions at much broader time-scale (correlation-based plasticity). Taken together, these results argue for an important role of spontaneous yet highly non-random activity, along with temporally precise learning rules, in the formation of neural circuits.}, Author = {Thivierge, Jean-Philippe}, Date-Added = {2012-07-06 13:56:12 +0000}, Date-Modified = {2012-07-06 13:57:01 +0000}, Doi = {10.1016/j.neunet.2009.01.001}, Journal = {Neural Netw}, Journal-Full = {Neural networks : the official journal of the International Neural Network Society}, Keywords = {21 Activity-development; Structure-Activity Relationship; Neurophysiology; Theoretical; Computational Biology; Spontaneous activity; topographic map; retinal wave paper}, Mesh = {Action Potentials; Animals; Brain; Computer Simulation; Humans; Models, Neurological; Nerve Net; Neuronal Plasticity; Neurons; Nonlinear Dynamics; Retina; Statistics as Topic; Synapses; Time Factors; Visual Pathways}, Month = {Sep}, Number = {7}, Pages = {901-12}, pmid = {19196491}, Pst = {ppublish}, Title = {How does non-random spontaneous activity contribute to brain development?}, Volume = {22}, Year = {2009}, url = {papers/Thivierge_NeuralNetw2009.pdf}} @article{Kerschensteiner:2008, Abstract = {Patterns of coordinated spontaneous activity have been proposed to guide circuit refinement in many parts of the developing nervous system. It is unclear, however, how such patterns, which are thought to indiscriminately synchronize nearby cells, could provide the cues necessary to segregate functionally distinct circuits within overlapping cell populations. Here, we report that glutamatergic retinal waves possess a substructure in the bursting of neighboring retinal ganglion cells with opposite light responses (ON or OFF). Within a wave, cells fire repetitive nonoverlapping bursts in a fixed order: ON before OFF. This pattern is absent from cholinergic waves, which precede glutamate-dependent activity, providing a developmental sequence of distinct activity-encoded cues. Asynchronous bursting of ON and OFF retinal ganglion cells depends on inhibition between these parallel pathways. Similar asynchronous activity patterns could arise throughout the nervous system, as inhibition matures and might help to separate connections of functionally distinct subnetworks.}, Author = {Kerschensteiner, Daniel and Wong, Rachel O L}, Date-Added = {2012-07-06 13:52:12 +0000}, Date-Modified = {2013-08-28 14:27:08 +0000}, Doi = {10.1016/j.neuron.2008.04.025}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {retinal wave paper; Spontaneous activity; 21 Activity-development; retina; Retinal Ganglion Cells/drug effects/physiology; visual system; topographic map; mouse; currOpinRvw}, Mesh = {Action Potentials; Animals; Mice; Mice, Inbred C57BL; Nerve Net; Neural Inhibition; Photic Stimulation; Retinal Ganglion Cells; Time Factors; Visual Pathways}, Month = {Jun}, Number = {6}, Pages = {851-8}, Pmc = {PMC2553397}, pmid = {18579076}, Pst = {ppublish}, Title = {A precisely timed asynchronous pattern of ON and OFF retinal ganglion cell activity during propagation of retinal waves}, Volume = {58}, Year = {2008}, url = {papers/Kerschensteiner_Neuron2008.pdf}} @article{Demas:2006, Abstract = {Axon terminals from the two eyes initially overlap in the dorsal-lateral geniculate nucleus (dLGN) but subsequently refine to occupy nonoverlapping territories. Retinal activity is required to establish and maintain this segregation. We show that despite the presence of retinal activity, segregated projections desegregate when the structure of activity is altered. Early in development, spontaneous retinal activity in the no b-wave (nob) mouse is indistinguishable from that of wild-type mice, and eye-specific segregation proceeds normally. But, around eye-opening, spontaneous and visually evoked activity in nob retinas become abnormal, coincident with a failure to preserve precise eye-specific territories. Dark-rearing studies suggest that altered visual experience is not responsible. Transgenic rescue of the mutated protein (nyctalopin) within nob retinal interneurons, without rescuing expression in either retinal projection neurons or their postsynaptic targets in the dLGN, restores spontaneous retinal activity patterns and prevents desegregation. Thus, normally structured spontaneous retinal activity stabilizes newly refined retinogeniculate circuitry.}, Author = {Demas, Jay and Sagdullaev, Botir T and Green, Erick and Jaubert-Miazza, Lisa and McCall, Maureen A and Gregg, Ronald G and Wong, Rachel O L and Guido, William}, Date-Added = {2012-07-06 13:48:47 +0000}, Date-Modified = {2013-08-27 20:42:46 +0000}, Doi = {10.1016/j.neuron.2006.03.033}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {retinal wave paper; Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; topographic map; visual system; LGN; mouse; currOpinRvw}, Mesh = {Animals; Body Patterning; Brain Mapping; Geniculate Bodies; Image Processing, Computer-Assisted; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mutation; Proteoglycans; Retina; Retinal Ganglion Cells; Reverse Transcriptase Polymerase Chain Reaction; Visual Pathways}, Month = {Apr}, Number = {2}, Pages = {247-59}, pmid = {16630836}, Pst = {ppublish}, Title = {Failure to maintain eye-specific segregation in nob, a mutant with abnormally patterned retinal activity}, Volume = {50}, Year = {2006}, url = {papers/Demas_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.03.033}} @article{Tribollet:2004, Abstract = {The distribution in the rat brain of high affinity nicotinic heteromeric acetylcholine receptors and of low affinity nicotinic, alpha7-containing, homomeric receptors was studied using in vitro light microscopic autoradiography. As ligands, we used [3H]epibatidine, or [125I]epibatidine, and [125I]alpha-bungarotoxin, respectively. In adult animals, the two types of binding sites were widely distributed in many different brain structures, including the brainstem, cerebellum, mesencephalic structures, limbic system and cortex, but their anatomical distribution differed markedly. Only in rare instances could a co-localization be observed, for example in the superficial layer of the superior colliculus. In developing animals, both types of labeling were strongly expressed during embryonic and postnatal phases. Their distributions were qualitatively similar to those observed in adult animals, with a few noticeable exceptions in the cerebral cortex, hippocampus and brain stem. In aging animals, neither the distribution nor the density of nicotinic binding sites was significantly altered. Our conclusions are the following. (a) There is little overlap in the distribution of heteromeric and alpha7-containing homomeric nicotinic receptors in the rat brain. (b) The abundance of neuronal nicotinic receptors during embryonic and postnatal development suggests that they may play a role in the establishment of neuronal connectivity. (c) The expression of neuronal nicotinic receptors is unaltered in middle aged animals, suggesting that in the rat these receptors do not play any major role in aging process.}, Author = {Tribollet, E and Bertrand, D and Marguerat, A and Raggenbass, M}, Date-Added = {2012-07-05 22:02:29 +0000}, Date-Modified = {2012-07-05 22:03:48 +0000}, Doi = {10.1016/j.neuroscience.2003.09.028}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {epibatidine; Nicotinic; Acetylcholine; Cholinergic; expression; rat}, Mesh = {Age Factors; Aging; Animals; Animals, Newborn; Autoradiography; Bicyclo Compounds, Heterocyclic; Binding Sites; Brain; Brain Chemistry; Bungarotoxins; Embryo, Mammalian; Female; Iodine Isotopes; Male; Nicotinic Agonists; Pyridines; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptors, Nicotinic; Tissue Distribution; Tritium}, Number = {2}, Pages = {405-20}, pmid = {14980390}, Pst = {ppublish}, Title = {Comparative distribution of nicotinic receptor subtypes during development, adulthood and aging: an autoradiographic study in the rat brain}, Volume = {124}, Year = {2004}, url = {papers/Tribollet_Neuroscience2004.pdf}} @article{Naeff:1992, Abstract = {The ontogeny of high affinity nicotinic cholinergic binding sites was studied in Long-Evans rat brain by in vitro autoradiography, using [3H]nicotine (10 nM) and cold (-)nicotine bitartrate to assess specificity. The first binding sites become detectable in spinal cord and caudal medulla oblongata at gestational day (GD) 12. Until GD 14, labelling spreads throughout lower brainstem, mesencephalon and parts of diencephalon, with higher densities in ventral areas (including the area of developing mesencephalic dopamine neurons). Matrix zones remain unlabelled. Receptor sites appear in the cerebellar anlage by GD 15, and in caudal caudate-putamen by GD 16. During development from late gestational to early postnatal stages, labelling is reduced in many lower brainstem areas and increases in forebrain, in particular in neocortex. Receptor density remains high in thalamus. In neocortex, nicotinic receptor sites are first seen in the subplate layer by GD 20. Labelling of this zone remains prominent until PN 14, when an additional band of increased receptor density is seen in cortical layers III/IV which contain high receptor levels in adulthood. At PN 27, the pattern has become similar to the adult one. The development of [3H]nicotine-binding sites in individual brain regions, with a general caudo-rostral gradient, accompanies cell differentiation and early synapse formation, e.g., in neocortex. The ontogenetic pattern differs in detail from that of muscarinic-cholinergic binding sites. The early presence of binding sites provides a basis for specific actions of nicotine on the fetal brain. As a consequence of the ontogenetic changes, different brain structures become targets for the action of this drug at different stages of development.}, Author = {Naeff, B and Schlumpf, M and Lichtensteiger, W}, Date-Added = {2012-07-05 21:37:19 +0000}, Date-Modified = {2012-07-05 22:01:57 +0000}, Journal = {Brain Res Dev Brain Res}, Journal-Full = {Brain research. Developmental brain research}, Keywords = {epibatidine; Acetylcholine; Cholinergic; expression; development; rat}, Mesh = {Animals; Autoradiography; Brain; Embryonic and Fetal Development; Gestational Age; Nicotine; Rats; Receptors, Nicotinic; Tritium}, Month = {Aug}, Number = {2}, Pages = {163-74}, pmid = {1394965}, Pst = {ppublish}, Title = {Pre- and postnatal development of high-affinity [3H]nicotine binding sites in rat brain regions: an autoradiographic study}, Volume = {68}, Year = {1992}} @article{Sharma:2002, Abstract = {The finding that neuronal nicotinic acetylcholine receptors (nAChRs) are present in non-neuronal cells both within and outside the nervous system raises some interesting issues. The mechanisms underlying receptor signaling and its downstream consequences in these cells remain to be elucidated. Factors controlling the release of acetylcholine and the extent of its diffusion are likely to be different for these cells than for traditional neuronal synapses. Recent advances on the physiologic functions of some of these cell types have provided a better insight into possible functional roles for nAChRs in nonexcitable cells. The presence of nAChRs on these cells also implies a broader scope for the actions of nicotine that needs to be considered from a clinical viewpoint. Revealing the potential physiologic roles for nAChRs on nonexcitable cells is likely to provide a more complete understanding of cholinergic signaling.}, Author = {Sharma, Geeta and Vijayaraghavan, Sukumar}, Date-Added = {2012-07-05 21:15:53 +0000}, Date-Modified = {2012-07-05 21:16:43 +0000}, Doi = {10.1002/neu.10114}, Journal = {J Neurobiol}, Journal-Full = {Journal of neurobiology}, Keywords = {Acetylcholine; Cholinergic; epibatidine; glia; Oligodendroglia;}, Mesh = {Animals; Blood Cells; Endothelium, Vascular; Humans; Keratinocytes; Mice; Neuroglia; Receptors, Nicotinic; Respiratory Mucosa; Signal Transduction}, Month = {Dec}, Number = {4}, Pages = {524-34}, pmid = {12436417}, Pst = {ppublish}, Title = {Nicotinic receptor signaling in nonexcitable cells}, Volume = {53}, Year = {2002}, url = {papers/Sharma_JNeurobiol2002.pdf}} @article{Simon:1992, Abstract = {The topographic ordering of retinal connections in the rat superior colliculus emerges during early postnatal life from an initially diffuse projection. Disruption of N-methyl-D-aspartate (NMDA) receptor activity in the superior colliculus during this period interferes with map remodeling. In rats chronically treated with NMDA receptor antagonists during the first two postnatal weeks, aberrant axons remain and arborize at topographically incorrect sites. These results indicate that, at a stage preceding visually evoked activity, normal NMDA receptor function is important for the development of an ordered neural map in the mammalian brain.}, Author = {Simon, D K and Prusky, G T and O'Leary, D D and Constantine-Paton, M}, Date-Added = {2012-07-05 21:03:42 +0000}, Date-Modified = {2012-07-05 21:04:36 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Activity-development; rat; Superior Colliculus; Structure-Activity Relationship; structural remodeling; Competitive Behavior; interaction; retina; N-Methyl-D-Aspartate}, Mesh = {2-Amino-5-phosphonovalerate; Aging; Animals; Axons; Dihydro-beta-Erythroidine; Dizocilpine Maleate; Drug Implants; Polyvinyls; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Superior Colliculi}, Month = {Nov}, Number = {22}, Pages = {10593-7}, Pmc = {PMC50387}, pmid = {1359542}, Pst = {ppublish}, Title = {N-methyl-D-aspartate receptor antagonists disrupt the formation of a mammalian neural map}, Volume = {89}, Year = {1992}, url = {papers/Simon_ProcNatlAcadSciUSA1992.pdf}} @article{Huberman:2002, Abstract = {To determine whether there is a critical period for development of eye-specific layers in the lateral geniculate nucleus (LGN), we prevented the normal segregation of retinogeniculate afferents and then allowed an extended period of time for recovery. After recovery, both anatomy and physiology revealed strictly nonoverlapping territories of input from the two eyes. However, the normal stereotyped pattern of eye-specific afferent and cellular layers never developed. Instead, the eye-specific territories of afferent input emerged as variable and disorganized patches with no corresponding interlaminar spaces in the LGN. These findings reveal a critical period for coordinating the development of three processes in the LGN: the segregation of afferents from the two eyes, the spatial organization of those afferents into layers, and the alignment of postsynaptic cytoarchitecture with the afferent inputs. We also assessed the physiological consequences of preventing normal lamination and found normal single-cell responses and topographic representation of visual space in the LGN. Clusters of ON-center and OFF-center LGN cells were segregated from one another as in normal animals. However, the organization of ON and OFF sublaminas in the treated animals was disrupted.}, Author = {Huberman, Andrew D and Stellwagen, David and Chapman, Barbara}, Date-Added = {2012-07-05 20:50:10 +0000}, Date-Modified = {2012-07-06 13:37:44 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retinal wave paper; epibatidine; visual system; retina; LGN; Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; structural remodeling; Ferrets}, Mesh = {Aging; Animals; Bicyclo Compounds, Heterocyclic; Cholera Toxin; Critical Period (Psychology); Drug Administration Routes; Electrodes, Implanted; Eye; Ferrets; Fluorescein; Geniculate Bodies; Pyridines; Recovery of Function; Retina; Retinal Ganglion Cells; Rhodamines; Visual Fields; Visual Pathways}, Month = {Nov}, Number = {21}, Pages = {9419-29}, Pmc = {PMC2662346}, pmid = {12417667}, Pst = {ppublish}, Title = {Decoupling eye-specific segregation from lamination in the lateral geniculate nucleus}, Volume = {22}, Year = {2002}, url = {papers/Huberman_JNeurosci2002.pdf}} @article{Marks:2002, Abstract = {The beta2 nicotinic acetylcholine receptor subunit null mutation eliminated most high affinity [(3) H]epibatidine binding in mouse brain, but significant binding remained in accessory olfactory nucleus, medial habenula, inferior colliculus and interpeduncular nucleus. Residual [(125) I]epibatidine binding sites in the inferior colliculus and interpeduncular nucleus were subsequently characterized. Inhibition of [(125) I]epibatidine binding by 12 agonists and six antagonists was very similar in these regions. Most acetylcholine-stimulated (86) Rb(+) efflux is eliminated in thalamus and superior colliculus of beta2 null mutants, but significant activity remained in inferior colliculus and interpeduncular nucleus. This residual activity was subsequently characterized. The 12 nicotinic agonists tested elicited concentration-dependent (86) Rb(+) efflux. Epibatidine was the most potent agonist. Cytisine was also potent and efficacious. EC(50) values for quaternary agonists were relatively high. Cytisine-stimulated (86) Rb(+) efflux was inhibited by six classical nicotinic antagonists. Mecamylamine and D-tubocurarine were most potent, while decamethonium was the least potent. Agonists and antagonists exhibited similar potency in both brain regions. Alpha-bungarotoxin (100 nm) did not significantly inhibit cytisine-stimulated (86) Rb(+) efflux, while the alpha3beta4 selective antagonist, alphaConotoxinAuIB, inhibited a significant fraction of the response in both brain regions. Thus, beta2 null mutant mice express residual nicotinic activity with properties resembling those of alpha3beta4*-nAChR.}, Author = {Marks, Michael J and Whiteaker, Paul and Grady, Sharon R and Picciotto, Marina R and McIntosh, J Michael and Collins, Allan C}, Date-Added = {2012-07-05 20:40:09 +0000}, Date-Modified = {2012-07-05 20:41:16 +0000}, Journal = {J Neurochem}, Journal-Full = {Journal of neurochemistry}, Keywords = {epibatidine}, Mesh = {Acetylcholine; Alkaloids; Animals; Azocines; Bicyclo Compounds, Heterocyclic; Binding, Competitive; Dose-Response Relationship, Drug; Inferior Colliculi; Iodine Radioisotopes; Mesencephalon; Mice; Mice, Mutant Strains; Nicotinic Agonists; Nicotinic Antagonists; Pyridines; Quinolizines; Receptors, Nicotinic; Rubidium Radioisotopes; Tritium}, Month = {Jun}, Number = {5}, Pages = {1102-15}, pmid = {12065623}, Pst = {ppublish}, Title = {Characterization of [(125) I]epibatidine binding and nicotinic agonist-mediated (86) Rb(+) efflux in interpeduncular nucleus and inferior colliculus of beta2 null mutant mice}, Volume = {81}, Year = {2002}, url = {papers/Marks_JNeurochem2002.pdf}} @article{Marks:1996, Abstract = {The effects of the nicotinic agonists acetylcholine, (+)-anatox in-a, carbachol, cytisine, dimethylphenylpiperazinum, (+)-epibatidine, (-)-epibatidine, methylcarbachol, D-nicotine, L-nicotine, and tetramethylammonium on 86Rb+ efflux from mouse thalamic synaptosomes were investigated. All 11 agonists evoked a concentration-dependent stimulation of 86Rb+ efflux as well as a time- and concentration-dependent reduction of response (desensitization). The agonists varied widely in potency, efficacy and rate of desensitization. (+)-Epibatidine was the most potent agonist (EC50 = 10 nM), whereas tetramethylammonium was the least potent (EC50 = 65 microM). The agonists containing a quaternary ammonium group were generally more efficacious than the other agonists, except for both of the enantiomers of epibatidine, which stimulated 86Rb+ efflux at least as well as acetylcholine. Cytisine was the least efficacious compound tested with a maximal response approximately 10% that of (-)-epibatidine. Exposure of the thalamic synaptosomes to agonist concentrations that generally stimulated little or no efflux reduced in a concentration-dependent manner a subsequent response to 10 microM nicotine. The IC50 values for this functional blockade (desensitization) were highly correlated with the Ki values for the inhibition of [3H]nicotine binding. Furthermore, exposure of the thalamic synaptosomes to 300 nM L-nicotine reduced the responses evoked by a subsequent exposure to a stimulating concentration of all 11 agonists. The observation of desensitization by both stimulating and substimulating concentrations of each agonist is consistent with the predictions of the two-state model of Katz and Thesleff.}, Author = {Marks, M J and Robinson, S F and Collins, A C}, Date-Added = {2012-07-05 19:50:45 +0000}, Date-Modified = {2012-07-05 20:22:48 +0000}, Journal = {J Pharmacol Exp Ther}, Journal-Full = {The Journal of pharmacology and experimental therapeutics}, Keywords = {epibatidine; Cholinergic; Acetylcholine; agonist; Drug}, Mesh = {Acetylcholine; Animals; Carbachol; Dose-Response Relationship, Drug; Female; Kinetics; Mice; Mice, Inbred C57BL; Nicotine; Rubidium Radioisotopes; Synaptosomes; Thalamus}, Month = {Jun}, Number = {3}, Pages = {1383-96}, pmid = {8667201}, Pst = {ppublish}, Title = {Nicotinic agonists differ in activation and desensitization of 86Rb+ efflux from mouse thalamic synaptosomes}, Volume = {277}, Year = {1996}, url = {papers/Marks_JPharmacolExpTher1996.pdf}} @article{Muir-Robinson:2002, Abstract = {Spontaneous retinal activity mediated by cholinergic transmission regulates the segregation of retinal ganglion cell axons in the lateral geniculate nucleus of the thalamus into eye-specific layers. The details of how the layers form are unknown. Mice lacking the beta2 subunit of the neuronal nicotinic acetylcholine receptor lack ACh-mediated waves and as a result, do not form eye-specific layers at any stage of development. However, during the second postnatal week, beta2-/- mice have glutamate-mediated waves. Here we show that after the first postnatal week, even in the absence of layers, retinothalamic axons segregate into an unlayered, patchy distribution of eye-specific regions. These results indicate that spontaneous neural activity may independently regulate eye-specific segregation and the formation of layers at the developing retinothalamic projection.}, Author = {Muir-Robinson, Gianna and Hwang, Bryan J and Feller, Marla B}, Date-Added = {2012-06-28 20:27:06 +0000}, Date-Modified = {2012-06-28 20:28:10 +0000}, Doi = {20026563}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; structural remodeling; Structure-Activity Relationship; Spontaneous activity; retinal wave paper; retina; mouse; visual system; LGN}, Mesh = {Animals; Axons; Geniculate Bodies; Kinetics; Mice; Mice, Knockout; Receptors, Glutamate; Receptors, Nicotinic; Retina; Retinal Ganglion Cells; Visual Pathways}, Month = {Jul}, Number = {13}, Pages = {5259-64}, pmid = {12097474}, Pst = {ppublish}, Title = {Retinogeniculate axons undergo eye-specific segregation in the absence of eye-specific layers}, Volume = {22}, Year = {2002}, url = {papers/Muir-Robinson_JNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/20026563}} @article{Pfeiffenberger:2005, Abstract = {In mammals, retinal ganglion cell (RGC) projections initially intermingle and then segregate into a stereotyped pattern of eye-specific layers in the dorsal lateral geniculate nucleus (dLGN). Here we found that in mice deficient for ephrin-A2, ephrin-A3 and ephrin-A5, eye-specific inputs segregated but the shape and location of eye-specific layers were profoundly disrupted. In contrast, mice that lacked correlated retinal activity did not segregate eye-specific inputs. Inhibition of correlated neural activity in ephrin mutants led to overlapping retinal projections that were located in inappropriate regions of the dLGN. Thus, ephrin-As and neural activity act together to control patterning of eye-specific retinogeniculate layers.}, Author = {Pfeiffenberger, Cory and Cutforth, Tyler and Woods, Georgia and Yamada, Jena and Renter{\'\i}a, Ren{\'e} C and Copenhagen, David R and Flanagan, John G and Feldheim, David A}, Date-Added = {2012-06-28 19:52:47 +0000}, Date-Modified = {2013-08-27 20:44:30 +0000}, Doi = {10.1038/nn1508}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Activity-development; epibatidine; Spontaneous activity; LGN; retina; Mouse; retinal wave paper; currOpinRvw}, Mesh = {Animals; Body Patterning; Brain Mapping; Ephrin-A2; Ephrin-A3; Ephrin-A5; Geniculate Bodies; Mice; Mice, Knockout; Receptor, EphA2; Receptor, EphA3; Receptor, EphA5; Retinal Ganglion Cells; Synaptic Transmission; Visual Pathways}, Month = {Aug}, Number = {8}, Pages = {1022-7}, Pmc = {PMC1352169}, pmid = {16025107}, Pst = {ppublish}, Title = {Ephrin-As and neural activity are required for eye-specific patterning during retinogeniculate mapping}, Volume = {8}, Year = {2005}, url = {papers/Pfeiffenberger_NatNeurosci2005.pdf}} @article{Bonetti:2010, Abstract = {The relative contribution of extrinsic and intrinsic mechanisms to cortical development is an intensely debated issue and an outstanding question in neurobiology. Currently, the emerging view is that interplay between intrinsic genetic mechanisms and extrinsic information shape different stages of cortical development. Yet, whereas the intrinsic program of early neocortical developmental events has been at least in part decoded, the exact nature and impact of extrinsic signaling are still elusive and controversial. We found that in the mouse developing visual system, acute pharmacological inhibition of spontaneous retinal activity (retinal waves-RWs) during embryonic stages increase the rate of corticogenesis (cell cycle withdrawal). Furthermore, early perturbation of retinal spontaneous activity leads to changes of cortical layer structure at a later time point. These data suggest that mouse embryonic retina delivers long-distance information capable of modulating cell genesis in the developing visual cortex and that spontaneous activity is the candidate long-distance acting extrinsic cue mediating this process. In addition, these data may support spontaneous activity to be a general signal coordinating neurogenesis in other developing sensory pathways or areas of the central nervous system.}, Author = {Bonetti, Ciro and Surace, Enrico Maria}, Date-Added = {2012-06-28 19:43:31 +0000}, Date-Modified = {2012-06-28 19:45:27 +0000}, Doi = {10.1371/journal.pone.0015211}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {21 Activity-development; Neocortex; visual system; retina; Superior Colliculus; neurogenesis; Pyramidal Cells; Embryo and Fetal Development; Mouse; retinal wave paper; Spontaneous activity; grants}, Mesh = {Animals; Bromodeoxyuridine; Central Nervous System; Cerebral Cortex; Forskolin; Gene Expression Regulation, Developmental; Immunohistochemistry; In Situ Hybridization; Injections, Intraocular; Ki-67 Antigen; Mice; Models, Biological; Retina; Time Factors; Visual Cortex}, Number = {12}, Pages = {e15211}, Pmc = {PMC2999540}, pmid = {21170332}, Pst = {epublish}, Title = {Mouse embryonic retina delivers information controlling cortical neurogenesis}, Volume = {5}, Year = {2010}, url = {papers/Bonetti_PLoSOne2010.pdf}} @article{Schafer:2012, Abstract = {Microglia are the resident CNS immune cells and active surveyors of the extracellular environment. While past work has focused on the role of these cells during disease, recent imaging studies reveal dynamic interactions between microglia and synaptic elements in the healthy brain. Despite these intriguing observations, the precise function of microglia at remodeling synapses and the mechanisms that underlie microglia-synapse interactions remain elusive. In the current study, we demonstrate a role for microglia in activity-dependent synaptic pruning in the postnatal retinogeniculate system. We show that microglia engulf presynaptic inputs during peak retinogeniculate pruning and that engulfment is dependent upon neural activity and the microglia-specific phagocytic signaling pathway, complement receptor 3(CR3)/C3. Furthermore, disrupting microglia-specific CR3/C3 signaling resulted in sustained deficits in synaptic connectivity. These results define a role for microglia during postnatal development and identify underlying mechanisms by which microglia engulf and remodel developing synapses.}, Author = {Schafer, Dorothy P and Lehrman, Emily K and Kautzman, Amanda G and Koyama, Ryuta and Mardinly, Alan R and Yamasaki, Ryo and Ransohoff, Richard M and Greenberg, Michael E and Barres, Ben A and Stevens, Beth}, Date-Added = {2012-05-29 14:06:16 +0000}, Date-Modified = {2016-02-26 17:53:25 +0000}, Doi = {10.1016/j.neuron.2012.03.026}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development; microglia; macrophage; structural remodeling; Structure-Activity Relationship; neuron; Neuron-Glia/*physiology}, Month = {May}, Number = {4}, Pages = {691-705}, pmid = {22632727}, Pst = {ppublish}, Title = {Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner}, Volume = {74}, Year = {2012}, url = {papers/Schafer_Neuron2012.pdf}} @article{Minlebaev:2011, Abstract = {During development, formation of topographic maps in sensory cortex requires precise temporal binding in thalamocortical networks. However, the physiological substrate for such synchronization is unknown. We report that early gamma oscillations (EGOs) enable precise spatiotemporal thalamocortical synchronization in the neonatal rat whisker sensory system. Driven by a thalamic gamma oscillator and initially independent of cortical inhibition, EGOs synchronize neurons in a single thalamic barreloid and corresponding cortical barrel and support plasticity at developing thalamocortical synapses. We propose that the multiple replay of sensory input in thalamocortical circuits during EGOs allows thalamic and cortical neurons to be organized into vertical topographic functional units before the development of horizontal binding in adult brain.}, Author = {Minlebaev, Marat and Colonnese, Matthew and Tsintsadze, Timur and Sirota, Anton and Khazipov, Roustem}, Date-Added = {2012-05-08 14:18:43 +0000}, Date-Modified = {2012-05-08 14:19:56 +0000}, Doi = {10.1126/science.1210574}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; oscillations; synchrony; Neocortex; Somatosensory Cortex; 21 Neurophysiology; in vivo; rat}, Mesh = {Animals; Animals, Newborn; Brain Waves; Evoked Potentials, Somatosensory; Excitatory Postsynaptic Potentials; Female; Inhibitory Postsynaptic Potentials; Interneurons; Male; Models, Neurological; Nerve Net; Neural Inhibition; Neuronal Plasticity; Neurons; Patch-Clamp Techniques; Rats; Rats, Wistar; Somatosensory Cortex; Synapses; Thalamus; Vibrissae}, Month = {Oct}, Number = {6053}, Pages = {226-9}, pmid = {21998388}, Pst = {ppublish}, Title = {Early γ oscillations synchronize developing thalamus and cortex}, Volume = {334}, Year = {2011}, url = {papers/Minlebaev_Science2011.pdf}, Bdsk-File-2 = {papers/Minlebaev_Science2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1210574}} @article{Zhou:1996, Abstract = {The membrane excitability of cholinergic (starburst) amacrine cells was studied in the rabbit retina during postnatal development. Whole-cell patch-clamp recordings were made from 110 displaced starburst cells in a thin retina] slice preparation of rabbits between postnatal days P1 and P56 old. We report that displaced starburst cells undergo a dramatic transition from spiking to nonspiking, caused by a loss of voltage-gated Na currents. This change in membrane excitability occurred just after eye opening (P10), such that all of the starburst cells tested before eye opening had conspicuous tetrodotoxin-sensitive Na currents and action potentials, but none tested after the first 3 postnatal weeks had detectable Na currents or spikes. Our results suggest that starburst cells use action potentials transiently during development and probably play a functional role in visual development. These cells then cease to spike as the retina matures, presumably consistent with their role in visual processing in the mature retina.}, Author = {Zhou, Z J and Fain, G L}, Date-Added = {2012-04-24 18:57:30 +0000}, Date-Modified = {2013-08-14 14:42:44 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {retinal waves; Rabbits; retina; in vitro; Patch-Clamp Techniques; spontaneous activity; activity-development}, Mesh = {Action Potentials; Aging; Animals; Animals, Newborn; Kinetics; Patch-Clamp Techniques; Rabbits; Retina; Retinal Ganglion Cells; Tetrodotoxin; Time Factors}, Month = {Jul}, Number = {15}, Pages = {8057-62}, Pmc = {PMC38874}, pmid = {8755602}, Pst = {ppublish}, Title = {Starburst amacrine cells change from spiking to nonspiking neurons during retinal development}, Volume = {93}, Year = {1996}, url = {papers/Zhou_ProcNatlAcadSciUSA1996.pdf}} @article{Lee:2006c, Abstract = {Patch-clamp recordings revealed that distal processes of starburst amacrine cells (SACs) received largely excitatory synaptic input from the receptive field center and nearly purely inhibitory inputs from the surround during both stationary and moving light stimulations. The direct surround inhibition was mediated mainly by reciprocal GABA(A) synapses between opposing SACs, which provided leading and prolonged inhibition during centripetal stimulus motion. Simultaneous Ca(2+) imaging and current-clamp recording during apparent-motion stimulation further demonstrated the contributions of both centrifugal excitation and GABA(A/C)-receptor-mediated centripetal inhibition to the direction-selective Ca(2+) responses in SAC distal processes. Thus, by placing GABA release sites in electrotonically semi-isolated distal processes and endowing these sites with reciprocal GABA(A) synapses, SACs use a radial-symmetric center-surround receptive field structure to build a polar-asymmetric circuitry. This circuitry may integrate at least three levels of interactions--center excitation, surround inhibition, and reciprocal inhibitions that amplify the center--surround antagonism-to generate robust direction selectivity in the distal processes.}, Author = {Lee, Seunghoon and Zhou, Z Jimmy}, Date-Added = {2012-04-24 18:50:34 +0000}, Date-Modified = {2012-04-24 18:55:15 +0000}, Doi = {10.1016/j.neuron.2006.08.007}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {retina; direction; topographic map; function; 21 Activity-development; 21 Neurophysiology; Patch-Clamp Techniques; Retinal Ganglion Cells; Amacrine Cells; connectivity; inhibition; GABA}, Mesh = {Action Potentials; Amacrine Cells; Animals; Cadmium; Calcium; Cells, Cultured; GABA Antagonists; Patch-Clamp Techniques; Phosphinic Acids; Potassium; Pyridazines; Pyridines; Rabbits; Receptors, GABA; Synaptic Transmission; gamma-Aminobutyric Acid}, Month = {Sep}, Number = {6}, Pages = {787-99}, pmid = {16982423}, Pst = {ppublish}, Title = {The synaptic mechanism of direction selectivity in distal processes of starburst amacrine cells}, Volume = {51}, Year = {2006}, url = {papers/Lee_Neuron2006.pdf}} @article{Syed:2004, Abstract = {We report here a systematic investigation of the dynamics, regulation and distribution of spontaneous waves in the rabbit retina during the course of wave development prior to eye opening. Three major findings were obtained in this longitudinal study. (1) Spontaneous retinal waves underwent three developmental stages, each of which displayed distinct wave dynamics, pharmacology and mechanism of generation and regulation. Stage I waves emerged prior to synaptogenesis and appeared as frequent, fast propagating waves that did not form spatial boundaries between waves. These waves could be inhibited by blockers of gap junctions and adenosine receptors, but not by nicotinic antagonists. Stage I waves lasted about one day (around embryonic day 22) and then switched rapidly to stage II, resulting in slower and less frequent waves that could be blocked by nicotinic antagonists and had a characteristic postwave refractory period and spatial boundaries between adjacent waves. Immediately after the transition from stage I to stage II, the waves could be reverted back to stage I by blocking nicotinic receptors, indicating the presence of mutually compensatory mechanisms for wave generation. Stage III waves emerged around postnatal day 3-4 (P3-4), and they were mediated by glutamtergic and muscarinic interactions. With age, these waves became weaker, more localized and less frequent. Spontaneous waves were rarely detected after P7. (2) GABA strongly modulated the wave dynamics in a stage- and receptor type-dependent manner. At stage I, endogenous GABAB activation downregulated the waves. The GABAB modulation disappeared during stage II and was replaced by a strong GABA(A/C)-mediated inhibition at stage III. Blocking GABA(A/C) receptors not only dramatically enhanced spontaneous stage III waves, but also induced propagating waves in >P7 retinas that did not show spontaneous waves, indicating a role of GABA inhibition in the disappearance of spontaneous waves. (3) Spontaneous retinal waves were found in both the inner and outer retina at all three stages. The waves in the outer retina (ventricular zone) also showed stage-dependent pharmacology and dynamics. Together, the results revealed a multistaged developmental sequence and stage-dependent dynamics, pharmacology and regulation of spontaneous retinal waves in the mammalian retina. The presence of retinal waves during multiple developmental stages and in multiple retinal layers suggests that the waves are a general developmental phenomenon with diverse functions.}, Author = {Syed, Mohsin Md and Lee, Seunghoon and Zheng, Jijian and Zhou, Z Jimmy}, Date-Added = {2012-04-24 18:46:14 +0000}, Date-Modified = {2012-04-24 18:47:00 +0000}, Doi = {10.1113/jphysiol.2004.066597}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {retinal wave paper; Spontaneous activity; development; Rabbits; retina; visual system; GABA}, Mesh = {Aging; Animals; Animals, Newborn; Electrophysiology; Embryo, Mammalian; Embryonic Development; Gap Junctions; Patch-Clamp Techniques; Rabbits; Receptors, GABA; Receptors, GABA-A; Receptors, GABA-B; Retina; gamma-Aminobutyric Acid}, Month = {Oct}, Number = {Pt 2}, Pages = {533-49}, Pmc = {PMC1665265}, pmid = {15308679}, Pst = {ppublish}, Title = {Stage-dependent dynamics and modulation of spontaneous waves in the developing rabbit retina}, Volume = {560}, Year = {2004}, url = {papers/Syed_JPhysiol2004.avi}, Bdsk-File-2 = {papers/Syed_JPhysiol2004.pdf}, Bdsk-File-3 = {papers/Syed_JPhysiol2004a.avi}, Bdsk-File-4 = {papers/Syed_JPhysiol2004a.pdf}, Bdsk-File-5 = {papers/Syed_JPhysiol2004b.avi}} @article{Zhang:2011a, Abstract = {Neural activity during vertebrate development has been unambiguously shown to play a critical role in sculpting circuit formation and function. Patterned neural activity in various parts of the developing nervous system is thought to modulate neurite outgrowth, axon targeting, and synapse refinement. The nature and role of patterned neural activity during development has been classically studied with in vitro preparations using pharmacological manipulations. In this review we discuss newly available and developing molecular-genetic tools for the visualization and manipulation of neural activity patterns specifically during development.}, Author = {Zhang, Jiayi and Ackman, James B and Dhande, Onkar S and Crair, Michael C}, Date-Added = {2012-04-24 17:53:59 +0000}, Date-Modified = {2012-04-24 17:54:30 +0000}, Doi = {10.3389/fnmol.2011.00043}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {review; optical imaging; optical physiology; Stimulation; Gene Expression}, Pages = {43}, Pmc = {PMC3219918}, pmid = {22121343}, Pst = {ppublish}, Title = {Visualization and manipulation of neural activity in the developing vertebrate nervous system}, Volume = {4}, Year = {2011}, url = {papers/Zhang_FrontMolNeurosci2011.pdf}} @article{Tritsch:2010a, Abstract = {We found rat central auditory neurons to fire action potentials in a precise sequence of mini-bursts before the age of hearing onset. This stereotyped pattern was initiated by hair cells in the cochlea, which trigger brief bursts of action potentials in auditory neurons each time they fire a Ca2+ spike. By generating theta-like activity, hair cells may limit the influence of synaptic depression in developing auditory circuits and promote consolidation of synapses.}, Author = {Tritsch, Nicolas X and Rodr{\'\i}guez-Contreras, Adri{\'a}n and Crins, Tom T H and Wang, Han Chin and Borst, J Gerard G and Bergles, Dwight E}, Date-Added = {2012-04-15 19:13:00 +0000}, Date-Modified = {2012-04-15 19:13:44 +0000}, Doi = {10.1038/nn.2604}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Spontaneous activity; Cochlear Nerve; Auditory Pathways; topographic map; tonotopy; development; 21 Activity-development; Neurophysiology}, Mesh = {Action Potentials; Animals; Animals, Newborn; Auditory Pathways; Calcium; Cochlea; Hair Cells, Auditory, Inner; Microelectrodes; Neurons; Olivary Nucleus; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Rats, Wistar; Spiral Ganglion; Time Factors}, Month = {Sep}, Number = {9}, Pages = {1050-2}, Pmc = {PMC2928883}, pmid = {20676105}, Pst = {ppublish}, Title = {Calcium action potentials in hair cells pattern auditory neuron activity before hearing onset}, Volume = {13}, Year = {2010}, url = {papers/Tritsch_NatNeurosci2010.pdf}, Bdsk-File-2 = {papers/Tritsch_NatNeurosci2010a.pdf}} @article{Nelson:1995, Abstract = {The emergence of functional lateral interactions in ferret visual cortex was monitored using high speed optical imaging of voltage-sensitive dye signals in brain slices. Prior to the time of eye opening, lateral activation was restricted to a narrow columnar region. During the week following eye opening, the extent of lateral propagation of activity more than doubled. Selective interruption of specific pathways in the slice, combined with pharmacological and anatomical experiments, determined that this lateral propagation was mediated by horizontal projections made within layer 2/3. These results indicate that functional horizontal interactions emerge only after axons begin branching and in parallel with, but not prior to, the refinement of orientation selectivity.}, Author = {Nelson, D A and Katz, L C}, Date-Added = {2012-04-14 21:09:12 +0000}, Date-Modified = {2012-04-14 21:10:38 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {circuit formation; connectivity; Neocortex; visual cortex; optical imaging; voltage sensor; in vitro; horizontal; development; 21 Activity-development; Neurophysiology}, Mesh = {Age Factors; Animals; Axons; Coloring Agents; Evoked Potentials, Visual; Ferrets; Image Processing, Computer-Assisted; Kynurenic Acid; Membrane Potentials; Neural Inhibition; Time Factors; Visual Cortex; Visual Pathways}, Month = {Jul}, Number = {1}, Pages = {23-34}, pmid = {7619527}, Pst = {ppublish}, Title = {Emergence of functional circuits in ferret visual cortex visualized by optical imaging}, Volume = {15}, Year = {1995}, url = {papers/Nelson_Neuron1995.pdf}} @article{Dalva:1994, Abstract = {Assessing patterns of synaptic connections in the developing mammalian neocortex has relied primarily on anatomical studies. In a physiological approach described here, the patterns of synaptic connections in slices of developing ferret visual cortex were determined with scanning laser photostimulation. Functional synaptic inputs to pyramidal cells in cortical layers 2 and 3 originating from sites close to the neuronal cell body appeared at least 2 weeks before eye opening, prior to the formation of long-range horizontal connections. Extensive long-range horizontal connections appeared in the next 10 days of development. The number of local connections peaked at the time of eye opening; the number of these connections subsequently declined to the level found in the adult while the specificity of long-distance connections increased. Thus, the relative influence of local connections on the activity of layer 2 and layer 3 neurons declines as the cortex matures while the influence of longer range connections increases substantially.}, Author = {Dalva, M B and Katz, L C}, Date-Added = {2012-04-14 20:58:33 +0000}, Date-Modified = {2012-04-14 21:03:23 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {development; circuit formation; connectivity; topographic map; connectivity; Neurophysiology; Stimulation; visual cortex; in vitro; Neocortex; visual system; 21 Activity-development}, Mesh = {Animals; Axons; Brain Mapping; Ferrets; Glutamates; Glutamic Acid; Light; Ocular Physiological Phenomena; Photic Stimulation; Pyramidal Cells; Receptors, Glutamate; Synapses; Visual Cortex}, Month = {Jul}, Number = {5169}, Pages = {255-8}, pmid = {7912852}, Pst = {ppublish}, Title = {Rearrangements of synaptic connections in visual cortex revealed by laser photostimulation}, Volume = {265}, Year = {1994}, url = {papers/Dalva_Science1994.pdf}} @article{Callaway:1991, Abstract = {Intrinsic horizontal axon collaterals in the striate cortex of adult cats specifically link columns having the same preferred orientation; consequently, retrograde tracer injections result in intrinsic labeling that is sharply clustered. We have previously shown that the normal development of this circuitry involves the emergence of crude clusters from an unclustered pattern during the second postnatal week. Crude clusters are later refined to the adult level of specificity by the selective rearrangement of axonal arbors that initially project to incorrect orientation columns. Here we report that depriving animals of patterned visual experience by binocular lid suture prior to natural eye opening had no discernible effect on the emergence of crude clusters. In contrast, cluster refinement was dramatically affected by binocular deprivation. Injections of retrograde tracers in the striate cortex of animals binocularly deprived for greater than 1 month revealed only crude clusters, indicating that horizontal axon collaterals projecting to incorrect orientation columns were retained well past the age when they normally would have been eliminated. Layer 2/3 pyramidal cells from 6-week-old binocularly deprived animals had abnormal distributions of intrinsic horizontal axon collaterals that mirrored the lack of cluster refinement. The radial clustering of their horizontal collaterals was considerably less precise than normal. These cells, nevertheless, developed many of the features of normal mature arbors, including the distal axonal branches not seen in arbors from younger animals with normal visual experience. Together, these results indicate that axonal rearrangements occurred, but with reduced specificity. Thus, binocular deprivation did not simply arrest the development of this orientation-specific circuit at an immature state but limited the accuracy with which axon collaterals were added or eliminated. We suggest that development of this orientation-specific circuitry, like ocular dominance column segregation, may depend on temporal correlation of activity for regulation of axonal rearrangement. The specificity of rearrangement may be degraded in binocularly deprived cats because they do not experience sharply oriented visual stimuli necessary for concurrent activation of same-orientation columns.}, Author = {Callaway, E M and Katz, L C}, Date-Added = {2012-04-14 20:51:25 +0000}, Date-Modified = {2012-04-14 20:56:46 +0000}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {circuit formation; Neocortex; cat; horizontal; connectivity; visual cortex; topographic map; development; 21 Activity-development; retrograde tracing}, Mesh = {Aging; Animals; Axonal Transport; Axons; Cats; Neurons; Reference Values; Sensory Deprivation; Vision, Binocular; Visual Cortex}, Month = {Feb}, Number = {3}, Pages = {745-9}, Pmc = {PMC50890}, pmid = {1704130}, Pst = {ppublish}, Title = {Effects of binocular deprivation on the development of clustered horizontal connections in cat striate cortex}, Volume = {88}, Year = {1991}, url = {papers/Callaway_ProcNatlAcadSciUSA1991.pdf}} @article{Katz:1993, Abstract = {New approaches for detecting and manipulating patterns of neuronal activity have revealed diverse strategies for constructing circuits in the developing brain. Spontaneously generated patterns can provide activity-based information before the onset of sensory inputs. In addition to mechanisms based on chemical synaptic communication, coordination of activity via gap junctions can provide important cues for synchronous activity early in circuit formation.}, Author = {Katz, L C}, Date-Added = {2012-04-14 20:45:16 +0000}, Date-Modified = {2012-04-14 20:48:19 +0000}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Spontaneous activity; Neocortex; Gap Junctions; synchrony; oscillations; development; circuit formation; review}, Mesh = {Animals; Cerebral Cortex; Humans; Neurons; Retina; Visual Pathways}, Month = {Feb}, Number = {1}, Pages = {93-99}, pmid = {8453297}, Pst = {ppublish}, Title = {Coordinate activity in retinal and cortical development}, Volume = {3}, Year = {1993}, url = {papers/Katz_CurrOpinNeurobiol1993.pdf}} @article{Weliky:1995, Abstract = {Combined optical imaging and electrophysiological techniques were used to assess directly the functional nature of long-range excitatory and inhibitory synaptic interactions between orientation columns in area 17 of ferret visual cortex. A significant correlation was found between the layout of iso-orientation columns and the pattern of evoked synaptic inputs between cortical sites: the largest-amplitude inhibitory and excitatory synaptic responses were evoked in single neurons when stimulation and recording electrodes were located in orientation columns sharing the same angle preference. Both excitatory and inhibitory synaptic responses decreased in amplitude when stimulation and recording electrodes were located in orientation columns with orthogonal angle preferences. Changing the stimulus intensity altered the balance of evoked excitation and inhibition without changing the columnar specificity of inputs. These results directly demonstrate that horizontal connections modulate both excitatory and inhibitory synaptic interactions between iso-orientation columns.}, Author = {Weliky, M and Kandler, K and Fitzpatrick, D and Katz, L C}, Date-Added = {2012-04-14 20:15:32 +0000}, Date-Modified = {2012-04-14 20:17:03 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {development; Neocortex; ferret; optical imaging; intrinsic signal; topographic map; Orientation; horizontal; connectivity; Neurophysiology; Patch-Clamp Techniques; structural remodeling;}, Mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Electric Conductivity; Electric Stimulation; Electrodes; Electrophysiology; Evoked Potentials; Ferrets; Fluorescent Dyes; Microspheres; Neurons; Patch-Clamp Techniques; Synapses; Visual Cortex}, Month = {Sep}, Number = {3}, Pages = {541-52}, pmid = {7546734}, Pst = {ppublish}, Title = {Patterns of excitation and inhibition evoked by horizontal connections in visual cortex share a common relationship to orientation columns}, Volume = {15}, Year = {1995}, url = {papers/Weliky_Neuron1995.pdf}} @article{Kandler:1998a, Abstract = {During brain development, endogenously generated coordinated neuronal activity regulates the precision of developing synaptic circuits (Shatz and Stryker, 1988; Weliky and Katz, 1997). In the neonatal neocortex, a form of endogenous coordinated activity is present as locally restricted intercellular calcium waves that are mediated by gap junctions (Yuste et al., 1992). As in other neuronal and non-neuronal systems, these coordinated calcium fluctuations may form the basis of functional cell assemblies (for review, seeWarner, 1992; Peinado et al., 1993b). In the present study, we investigated the cellular mechanisms that mediate the activation of neuronal domains and the propagation of intercellular calcium waves in slices from neonatal rat neocortex. The occurrence of neuronal domains did not depend on intercellular propagation of regenerative electrical signals because domains persisted after blockade of sodium and calcium-dependent action potentials. Neuronal domains were elicited by intracellular infusion of inositol trisphosphate (IP3) but not of calcium, indicating the involvement of IP3-related second-messenger systems. Pharmacological stimulation of metabotropic glutamate receptors, which are linked to the production of IP3, elicited similarly coordinated calcium increases, whereas pharmacological blockade of metabotropic glutamate receptors dramatically reduced the number of neuronal domains. Therefore, the propagating cellular signal that causes the occurrence of neuronal domains seems to be inositol trisphosphate but not calcium. Because coordination of neuronal calcium changes by gap junctions is independent of electrical signals, the function of gap junctions between neocortical neurons is probably to synchronize biochemical rather than electrical activity.}, Author = {Kandler, K and Katz, L C}, Date-Added = {2012-04-14 20:06:20 +0000}, Date-Modified = {2012-04-14 20:08:39 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity; Gap Junctions; rat; calcium imaging; Neurophysiology; 21 Activity-development}, Mesh = {Aging; Animals; Calcium; Gap Junctions; Inositol 1,4,5-Trisphosphate; Intracellular Membranes; Neurons; Rats; Receptors, Metabotropic Glutamate; Visual Cortex}, Month = {Feb}, Number = {4}, Pages = {1419-27}, pmid = {9454851}, Pst = {ppublish}, Title = {Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication}, Volume = {18}, Year = {1998}, url = {papers/Kandler_JNeurosci1998.pdf}} @article{Kandler:1998, Abstract = {Neuronal coupling by gap junctions is common during early development of the brain. Coupling is thought to create functional cell assemblies which may be involved in the functional specification of brain areas and the formation of synaptic circuits. In the present study we used slices from the visual cortex of postnatal ferrets to investigate the temporal relationship of gap junction coupling and formation of functional synapses. Individual neurons were filled with the gap-junction-permeable dye biotin ethylenediamine while spontaneous synaptic currents were recorded using whole-cell patch clamp recording techniques. We found that dye coupling increased during the first 2 postnatal weeks resulting at a peak around P14, after which coupling steadily decreased until adult levels were reached in animals older than P30. Spontaneous synaptic activity increased 30-fold between birth and maturity (from 10.8 +/- 2.4 to 318 +/- 54 events/min). The sharpest rise in synaptic activity, an over 5-fold increase, occurred between P15 and P19, shortly after the invasion of thalamocortical fibers.}, Author = {Kandler, K and Katz, L C}, Date-Added = {2012-04-14 20:00:37 +0000}, Date-Modified = {2012-04-14 20:01:34 +0000}, Journal = {Dev Neurosci}, Journal-Full = {Developmental neuroscience}, Keywords = {Spontaneous activity; development; Neurophysiology; 21 Activity-development; in vitro; ferret; Gap Junctions; Neocortex}, Mesh = {Animals; Biotin; Calcium; Cell Communication; Coloring Agents; Ferrets; Gap Junctions; Patch-Clamp Techniques; Second Messenger Systems; Synapses; Synaptic Transmission; Visual Cortex}, Number = {1}, Pages = {59-64}, pmid = {9600391}, Pst = {ppublish}, Title = {Relationship between dye coupling and spontaneous activity in developing ferret visual cortex}, Volume = {20}, Year = {1998}, url = {papers/Kandler_DevNeurosci1998.pdf}} @article{Zheng:2006a, Abstract = {Pharmacologically isolated starburst amacrine cells (SACs) in perinatal rabbit retinas spontaneously generated semiperiodic calcium spikes and long-lasting after-hyperpolarizations (AHPs), mediated by calcium-activated, cyclic AMP-sensitive potassium currents. These AHPs, rather than a depletion of neurotransmitters (as was previously believed), produced the refractory period of spontaneous retinal waves and set the upper limit of the wave frequency. Each SAC received inputs from roughly 10-30 neighboring SACs during a wave. These inputs synchronized and reshaped the intrinsic bursts to produce network oscillations at a rhythm different from that of individual SACs. With maturation, the semiperiodic bursts in SACs disappeared, owing to reduced intrinsic excitability and increased network inhibition. Thus, retinal waves are generated by a transient and specific network of cell-autonomous oscillators synchronized by reciprocally excitatory connections.}, Author = {Zheng, Jijian and Lee, Seunghoon and Zhou, Z Jimmy}, Date-Added = {2012-04-13 15:19:00 +0000}, Date-Modified = {2012-04-13 15:19:39 +0000}, Doi = {10.1038/nn1644}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {currOpinRvw; Spontaneous activity; retinal wave paper; 21 Activity-development; retina; visual system; Retinal Ganglion Cells; Amacrine Cells; 21 Neurophysiology}, Mesh = {Action Potentials; Amacrine Cells; Animals; Biological Clocks; Calcium; Calcium Signaling; Fura-2; Isoquinolines; Nerve Net; Patch-Clamp Techniques; Potassium Channels, Calcium-Activated; Rabbits; Retinal Ganglion Cells; Synaptic Transmission; Vision, Ocular; Visual Pathways}, Month = {Mar}, Number = {3}, Pages = {363-71}, pmid = {16462736}, Pst = {ppublish}, Title = {A transient network of intrinsically bursting starburst cells underlies the generation of retinal waves}, Volume = {9}, Year = {2006}, url = {papers/Zheng_NatNeurosci2006.pdf}} @article{Zariwala:2012, Abstract = {Fluorescent calcium indicator proteins, such as GCaMP3, allow imaging of activity in genetically defined neuronal populations. GCaMP3 can be expressed using various gene delivery methods, such as viral infection or electroporation. However, these methods are invasive and provide inhomogeneous and nonstationary expression. Here, we developed a genetic reporter mouse, Ai38, which expresses GCaMP3 in a Cre-dependent manner from the ROSA26 locus, driven by a strong CAG promoter. Crossing Ai38 with appropriate Cre mice produced robust GCaMP3 expression in defined cell populations in the retina, cortex, and cerebellum. In the primary visual cortex, visually evoked GCaMP3 signals showed normal orientation and direction selectivity. GCaMP3 signals were rapid, compared with virally expressed GCaMP3 and synthetic calcium indicators. In the retina, Ai38 allowed imaging spontaneous calcium waves in starburst amacrine cells during development, and light-evoked responses in ganglion cells in adult tissue. Our results show that the Ai38 reporter mouse provides a flexible method for targeted expression of GCaMP3.}, Author = {Zariwala, Hatim A and Borghuis, Bart G and Hoogland, Tycho M and Madisen, Linda and Tian, Lin and De Zeeuw, Chris I and Zeng, Hongkui and Looger, Loren L and Svoboda, Karel and Chen, Tsai-Wen}, Date-Added = {2012-04-10 15:52:50 +0000}, Date-Modified = {2012-04-10 15:54:05 +0000}, Doi = {10.1523/JNEUROSCI.4469-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {calcium imaging; optical physiology; multiphoton; microscopy; Technique; Mouse; Transgenic; gene; calcium sensor}, Month = {Feb}, Number = {9}, Pages = {3131-41}, Pmc = {PMC3315707}, pmid = {22378886}, Pst = {ppublish}, Title = {A Cre-dependent GCaMP3 reporter mouse for neuronal imaging in vivo}, Volume = {32}, Year = {2012}, url = {papers/Zariwala_JNeurosci2012.pdf}} @article{Vaney:2002, Abstract = {The neuronal circuitry underlying the generation of direction selectivity in the retina has remained elusive for almost 40 years. Recent studies indicate that direction selectivity may be established within the radial dendrites of 'starburst' amacrine cells and that retinal ganglion cells may acquire their direction selectivity by the appropriate weighting of excitatory and inhibitory inputs from starburst dendrites pointing in different directions. If so, this would require unexpected complexity and subtlety in the synaptic connectivity of these CNS neurons.}, Author = {Vaney, David I and Taylor, W Rowland}, Date-Added = {2012-04-09 17:15:21 +0000}, Date-Modified = {2012-04-09 17:16:46 +0000}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {review; visual system; retina; topographic map; sensory map; vision; GABA; interneurons; 21 Activity-development; circuit formation}, Mesh = {Amacrine Cells; Animals; Motion Perception; Neural Inhibition; Retina; Retinal Ganglion Cells; Synaptic Transmission}, Month = {Aug}, Number = {4}, Pages = {405-10}, pmid = {12139988}, Pst = {ppublish}, Title = {Direction selectivity in the retina}, Volume = {12}, Year = {2002}, url = {papers/Vaney_CurrOpinNeurobiol2002.pdf}} @article{Wei:2011, Abstract = {Establishing precise synaptic connections is crucial to the development of functional neural circuits. The direction-selective circuit in the retina relies upon highly selective wiring of inhibitory inputs from starburst amacrine cells (SACs) onto four subtypes of ON-OFF direction-selective ganglion cells (DSGCs), each preferring motion in one of four cardinal directions. It has been reported in rabbit that the SACs on the 'null' sides of DSGCs form functional GABA (γ-aminobutyric acid)-mediated synapses, whereas those on the preferred sides do not. However, it is not known how the asymmetric wiring between SACs and DSGCs is established during development. Here we report that in transgenic mice with cell-type-specific labelling, the synaptic connections from SACs to DSGCs were of equal strength during the first postnatal week, regardless of whether the SAC was located on the preferred or null side of the DSGC. However, by the end of the second postnatal week, the strength of the synapses made from SACs on the null side of a DSGC significantly increased whereas those made from SACs located on the preferred side remained constant. Blocking retinal activity by intraocular injections of muscimol or gabazine during this period did not alter the development of direction selectivity. Hence, the asymmetric inhibition between the SACs and DSGCs is achieved by a developmental program that specifically strengthens the GABA-mediated inputs from SACs located on the null side, in a manner not dependent on neural activity.}, Author = {Wei, Wei and Hamby, Aaron M and Zhou, Kaili and Feller, Marla B}, Date-Added = {2012-04-09 15:27:37 +0000}, Date-Modified = {2012-04-09 15:28:51 +0000}, Doi = {10.1038/nature09600}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {topographic map; visual system; retina; Retinal Ganglion Cells; direction; 21 Activity-development; Spontaneous activity; retinal wave paper; GABA; interneurons; 21 Neurophysiology}, Mesh = {Action Potentials; Amacrine Cells; Animals; Dendrites; Electric Conductivity; Mice; Mice, Transgenic; Models, Neurological; Motion; Motion Perception; Muscimol; Neural Inhibition; Neuronal Plasticity; Patch-Clamp Techniques; Photic Stimulation; Pyridazines; Retina; Retinal Ganglion Cells; Synapses; gamma-Aminobutyric Acid}, Month = {Jan}, Number = {7330}, Pages = {402-6}, pmid = {21131947}, Pst = {ppublish}, Title = {Development of asymmetric inhibition underlying direction selectivity in the retina}, Volume = {469}, Year = {2011}, url = {papers/Wei_Nature2011.pdf}} @article{Malsburg:1973, Author = {von der Malsburg, C}, Date-Added = {2012-02-29 17:18:49 -0500}, Date-Modified = {2012-02-29 17:28:06 -0500}, Journal = {Kybernetik}, Journal-Full = {Kybernetik}, Keywords = {Computational Biology; Theoretical; Models; network; visual cortex; visual system; Retina; Spontaneous activity; self organization; topographic map; development}, Mesh = {Animals; Cats; Cybernetics; Feedback; Learning; Models, Neurological; Neurons, Afferent; Orientation; Synapses; Visual Cortex}, Month = {Dec}, Number = {2}, Pages = {85-100}, pmid = {4786750}, Pst = {ppublish}, Title = {Self-organization of orientation sensitive cells in the striate cortex}, Volume = {14}, Year = {1973}, url = {papers/Malsburg_Kybernetik1973.pdf}} @article{Ragsdale:2001, Abstract = {When and how is the area map of the cerebral cortex set up during development? Recent studies indicate that regional pattern emerges early in cortical neurogenesis, and that this pattern does not require cues from extrinsic innervation. Studies of mutant mice indicate a role for embryonic signaling centers and for specific transcription factors in regionalizing the cortex. Thus, it is increasingly probable that the cortex is partitioned using the same types of mechanisms--and in some cases, the same gene families--that are used in patterning other parts of the embryo. This emerging model is likely to be the basis for many future studies. However, new evidence also confirms the special nature of the cerebral cortex, in that cues from developing connections appear to modify and refine the final area map.}, Author = {Ragsdale, C W and Grove, E A}, Date-Added = {2012-02-29 15:54:57 -0500}, Date-Modified = {2012-02-29 15:55:14 -0500}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {neocortex; review literature; patterning; topographic map; Somatosensory Cortex; Visual Cortex; genes; development; axon guidance; Thalamus}, Mesh = {Animals; Cerebral Cortex; Humans; Models, Biological; Protein Sorting Signals; Signal Transduction; Thalamus; Transcription, Genetic}, Month = {Feb}, Number = {1}, Pages = {50-8}, pmid = {11179872}, Pst = {ppublish}, Title = {Patterning the mammalian cerebral cortex}, Volume = {11}, Year = {2001}, url = {papers/Ragsdale_CurrOpinNeurobiol2001.pdf}} @article{Shimogori:2005, Abstract = {Thalamic innervation of each neocortical area is vital to cortical function, but the developmental strategies that guide axons to specific areas remain unclear. We took a new approach to determine the contribution of intracortical cues. The cortical patterning molecule fibroblast growth factor 8 (FGF8) was misexpressed in the cortical primordium to rearrange the area map. Thalamic axons faithfully tracked changes in area position and innervated duplicated somatosensory barrel fields induced by an ectopic source of FGF8, indicating that thalamic axons indeed use intracortical positional information. Because cortical layers are generated in temporal order, FGF8 misexpression at different ages could be used to shift regional identity in the subplate and cortical plate either in or out of register. Thalamic axons showed strikingly different responses in the two different conditions, disclosing sources of positional guidance in both subplate and cortical plate. Unexpectedly, axon trajectories indicated that an individual neocortical layer could provide not only laminar but also area-specific guidance. Our findings demonstrate that thalamocortical axons are directed by sequential, positional cues within the cortex and implicate FGF8 as an indirect regulator of thalamocortical innervation.}, Author = {Shimogori, Tomomi and Grove, Elizabeth A}, Date-Added = {2012-02-29 15:46:46 -0500}, Date-Modified = {2012-02-29 15:47:24 -0500}, Doi = {10.1523/JNEUROSCI.0453-05.2005}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {neocortex; FGF; Fibroblast Growth Factor; patterning; topographic map; Somatosensory Cortex; Visual Cortex; genes; development; Thalamus; axon guidance}, Mesh = {Animals; Axons; Electroporation; Fibroblast Growth Factor 8; Genes, Reporter; Genetic Vectors; Injections, Intraventricular; Mice; Neural Pathways; Receptor, Fibroblast Growth Factor, Type 3; Recombinant Fusion Proteins; Somatosensory Cortex; Telencephalon; Thalamus; Transfection; Vibrissae}, Month = {Jul}, Number = {28}, Pages = {6550-60}, pmid = {16014716}, Pst = {ppublish}, Title = {Fibroblast growth factor 8 regulates neocortical guidance of area-specific thalamic innervation}, Volume = {25}, Year = {2005}, url = {papers/Shimogori_JNeurosci2005.pdf}} @article{Grove:2008, Abstract = {The RIKEN Center for Developmental Biology recently held its 2008 Symposium ;Turning Neurons into a Nervous System' in Kobe, Japan. The program, organized by Masatoshi Takeichi, Joshua Sanes, Hideki Enomoto and Raj Ladher, provided a rich sampling from current work in developmental neurobiology. Researchers from Japan, Europe and the USA gathered at this meeting to share insights into neural development and to admire the opening of the cherry blossom season.}, Author = {Grove, Elizabeth A}, Date-Added = {2012-02-29 15:45:53 -0500}, Date-Modified = {2012-02-29 15:46:08 -0500}, Doi = {10.1242/dev.020511}, Journal = {Development}, Journal-Full = {Development (Cambridge, England)}, Keywords = {neocortex; review literature; patterning; topographic map; Somatosensory Cortex; Visual Cortex; genes; development}, Mesh = {Animals; Cell Differentiation; Cell Shape; Humans; Models, Biological; Nervous System; Neurons; Retinal Ganglion Cells}, Month = {Jul}, Number = {13}, Pages = {2203-6}, pmid = {18539920}, Pst = {ppublish}, Title = {Turning neurons into a nervous system}, Volume = {135}, Year = {2008}, url = {papers/Grove_Development2008.pdf}} @article{Toyoda:2010, Abstract = {Gain- and loss-of-function experiments have demonstrated that a source of fibroblast growth factor (FGF) 8 regulates anterior to posterior (A/P) patterning in the neocortical area map. Whether FGF8 controls patterning as a classic diffusible morphogen has not been directly tested. We report evidence that FGF8 diffuses through the mouse neocortical primordium from a discrete source in the anterior telencephalon, forms a protein gradient across the entire A/P extent of the primordium, and acts directly at a distance from its source to determine area identity. FGF8 immunofluorescence revealed FGF8 protein distributed in an A/P gradient. Fate-mapping experiments showed that outside the most anterior telencephalon, neocortical progenitor cells did not express Fgf8, nor were they derived from Fgf8-expressing cells, suggesting that graded distribution of FGF8 results from protein diffusion from the anterior source. Supporting this conclusion, a dominant-negative high-affinity FGF8 receptor captured endogenous FGF8 at a distance from the FGF8 source. New FGF8 sources introduced by electroporation showed haloes of FGF8 immunofluorescence indicative of FGF8 diffusion, and surrounding cells reacted to a new source of FGF8 by upregulating different FGF8-responsive genes in concentric domains around the source. Reducing endogenous FGF8 with the dominant-negative receptor in the central neocortical primordium induced cells to adopt a more posterior area identity, demonstrating long-range area patterning by FGF8. These observations support FGF8 as a classic diffusible morphogen in neocortex, thereby guiding future studies of neocortical pattern formation.}, Author = {Toyoda, Reiko and Assimacopoulos, Stavroula and Wilcoxon, Jennifer and Taylor, Albert and Feldman, Polina and Suzuki-Hirano, Asuka and Shimogori, Tomomi and Grove, Elizabeth A}, Date-Added = {2012-02-29 15:42:49 -0500}, Date-Modified = {2012-02-29 15:43:01 -0500}, Doi = {10.1242/dev.055392}, Journal = {Development}, Journal-Full = {Development (Cambridge, England)}, Keywords = {neocortex; review literature; patterning; topographic map; Somatosensory Cortex; Visual Cortex; genes; development}, Mesh = {Animals; Antibodies, Monoclonal; Body Patterning; Electroporation; Fibroblast Growth Factor 8; Fluorescent Antibody Technique; Gene Expression Regulation, Developmental; Immunohistochemistry; In Situ Hybridization; Mice; Microscopy, Confocal; Neocortex; Receptors, Fibroblast Growth Factor}, Month = {Oct}, Number = {20}, Pages = {3439-48}, Pmc = {PMC2947756}, pmid = {20843859}, Pst = {ppublish}, Title = {FGF8 acts as a classic diffusible morphogen to pattern the neocortex}, Volume = {137}, Year = {2010}, url = {papers/Toyoda_Development2010.pdf}} @article{Rash:2007, Abstract = {Division of the telencephalic vesicle into hemispheres and specification of the cerebral cortex are key stages in forebrain development. We investigate the interplay in these processes of Sonic hedgehog (Shh), fibroblast growth factors (Fgfs), and the transcription factor Gli3, which in its repressor form (Gli3R) antagonizes Shh signaling and downregulates expression of several Fgf genes. Contrary to previous reports, Shh is not required for dorsal hemisphere separation. Mice lacking Shh develop a dorsal telencephalic midline, a cortical hem, and two cortical hemispheres. The hemispheres do not divide rostrally, probably because of reduced local Fgf gene expression, resulting from the loss of Shh inhibition of Gli3R. Removing one functional copy of Gli3 substantially rescues Fgf expression and rostral telencephalic morphology. In mice lacking Gli3 function, cortical development is arrested, and ventral gene expression invades the dorsal telencephalon. These defects are potentially explained by disinhibition of Shh activity. However, when both copies of Shh are removed from Gli3-null mice, dorsal telencephalic defects persist. One such defect is a large dorsal expansion of the expression of Fgf genes. Fgf15 expression, for example, expands from a discrete ventral domain throughout the dorsal telencephalon. We propose that Fgf signaling, known to ventralize the telencephalon in a Shh-independent manner, suppresses cortical fate in the absence of Gli3. Our findings point away from Shh involvement in dorsal telencephalic patterning and encourage additional exploration of Fgf signaling and Gli3 repression in corticogenesis.}, Author = {Rash, Brian G and Grove, Elizabeth A}, Date-Added = {2012-02-29 15:41:17 -0500}, Date-Modified = {2012-02-29 15:41:23 -0500}, Doi = {10.1523/JNEUROSCI.3204-07.2007}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {neocortex; review literature; patterning; topographic map; Somatosensory Cortex; Visual Cortex; genes; development}, Mesh = {Animals; Gene Expression Regulation, Developmental; Hedgehog Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Telencephalon}, Month = {Oct}, Number = {43}, Pages = {11595-603}, pmid = {17959802}, Pst = {ppublish}, Title = {Patterning the dorsal telencephalon: a role for sonic hedgehog?}, Volume = {27}, Year = {2007}, url = {papers/Rash_JNeurosci2007.pdf}} @article{Rash:2006, Abstract = {Two anatomical patterns characterize the neocortex, and both are essential for normal cortical function. First, neocortex is divided into anatomically distinct and functionally specialized areas that form a species-specific map. Second, neocortex is composed of layers that organize cortical connectivity. Recent studies of layer and area development have used time-lapse microscopy to follow cortical cell division and migration, gene arrays to find layer- or area- specific regulatory genes, time- and region- specific manipulations of candidate genes, and optical imaging to compare area maps in wild type with genetically altered mice. New observations clarify the molecular and cellular mechanisms that generate each pattern, and stress the links between layer and area formation.}, Author = {Rash, Brian G and Grove, Elizabeth A}, Date-Added = {2012-02-29 15:38:01 -0500}, Date-Modified = {2013-05-21 19:47:22 +0000}, Doi = {10.1016/j.conb.2006.01.004}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {neocortex; review literature; patterning; topographic map; Somatosensory Cortex; Visual Cortex; genes; development; currOpinRvw}, Mesh = {Animals; Body Patterning; Cerebral Cortex; Cerebral Ventricles; Humans; Mammals; Neurons}, Month = {Feb}, Number = {1}, Pages = {25-34}, pmid = {16426837}, Pst = {ppublish}, Title = {Area and layer patterning in the developing cerebral cortex}, Volume = {16}, Year = {2006}, url = {papers/Rash_CurrOpinNeurobiol2006.pdf}} @article{Grove:2003, Abstract = {The view that the cortical primordium is initially patterned in similar ways to the rest of the embryo has been a conceptual breakthrough. We now have a new starting point for understanding how the cortical area map is established and how maps may change and evolve. Here we review findings that signaling molecules secreted from distinct cortical signaling centers establish positional information in the cortical primordium and regulate regional growth. In other embryonic systems, positional signals would regulate the patterned expression of transcription factors, leading, in a gene regulatory cascade, to the patterned differentiation of the tissue. We discuss candidate transcription factors with respect to such a model of cortical patterning. Finally, embryonic structures interact to pattern one another. We review data suggesting that the thalamus and cortex are patterned independently then interact to generate the final cortical area map.}, Author = {Grove, Elizabeth A and Fukuchi-Shimogori, Tomomi}, Date-Added = {2012-02-29 15:36:04 -0500}, Date-Modified = {2012-02-29 15:36:48 -0500}, Doi = {10.1146/annurev.neuro.26.041002.131137}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {neocortex; review literature; patterning; topographic map; Somatosensory Cortex; Visual Cortex; genes; development}, Mesh = {Animals; Body Patterning; Cerebral Cortex; DNA-Binding Proteins; Fibroblast Growth Factor 8; Fibroblast Growth Factors; Gene Expression Regulation, Developmental; Mice; Mice, Transgenic; Models, Neurological; Proto-Oncogene Proteins; Signal Transduction; Species Specificity; Thalamus; Transcription Factors; Wnt Proteins; Zebrafish Proteins}, Pages = {355-80}, pmid = {14527269}, Pst = {ppublish}, Title = {Generating the cerebral cortical area map}, Volume = {26}, Year = {2003}, url = {papers/Grove_AnnuRevNeurosci2003.pdf}} @article{Ford:2012, Abstract = {Before vision, a transient network of recurrently connected cholinergic interneurons, called starburst amacrine cells (SACs), generates spontaneous retinal waves. Despite an absence of robust inhibition, cholinergic retinal waves initiate infrequently and propagate within finite boundaries. Here, we combine a variety of electrophysiological and imaging techniques and computational modeling to elucidate the mechanisms underlying these spatial and temporal properties of waves in developing mouse retina. Waves initiate via rare spontaneous depolarizations of SACs. Waves propagate through recurrent cholinergic connections between SACs and volume release of ACh as demonstrated using paired recordings and a cell-based ACh optical sensor. Perforated-patch recordings and two-photon calcium imaging reveal that individual SACs have slow afterhyperpolarizations that induce SACs to have variable depolarizations during sequential waves. Using a computational model in which the properties of SACs are based on these physiological measurements, we reproduce the slow frequency, speed, and finite size of recorded waves. This study represents a detailed description of the circuit that mediates cholinergic retinal waves and indicates that variability of the interneurons that generate this network activity may be critical for the robustness of waves across different species and stages of development.}, Author = {Ford, Kevin J and F{\'e}lix, Aude L and Feller, Marla B}, Date-Added = {2012-02-24 16:44:04 -0500}, Date-Modified = {2012-02-24 16:45:02 -0500}, Doi = {10.1523/JNEUROSCI.5309-12.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retinal wave paper; Spontaneous activity; in vitro; retina; Acetylcholine; 21 Activity-development; 21 Neurophysiology; calcium imaging; Models; Theoretical; Patch-Clamp Techniques}, Month = {Jan}, Number = {3}, Pages = {850-63}, pmid = {22262883}, Pst = {ppublish}, Title = {Cellular mechanisms underlying spatiotemporal features of cholinergic retinal waves}, Volume = {32}, Year = {2012}, url = {papers/Ford_JNeurosci2012.pdf}} @article{Inta:2008, Abstract = {Most forebrain GABAergic interneurons in rodents are born during embryonic development in the ganglionic eminences (GE) and migrate tangentially into the cortical plate. A subset, however, continues to be generated postnatally in the subventricular zone (SVZ). These interneurons populate the olfactory bulb (OB) reached via migration in the rostral migratory stream (RMS). Employing transgenic mice expressing EGFP in 5-HT(3)-positive neurons, we identified additional migratory pathways in the early postnatal brain. Time-lapse imaging experiments revealed massive migration of EGFP-positive cells from the SVZ into numerous forebrain regions, including cortex, striatum, and nucleus accumbens. The neuronal fate of the migratory EGFP-labeled cells was indicated by their doublecortin (DCX) expression. Birthdating experiments, by using 5-bromo-2'-deoxyuridine (BrdU) and retrovirus-based experiments, provided evidence that migrating neuroblasts were born in the SVZ postnatally and developed a distinct GABAergic phenotype. Our results demonstrate that the SVZ is a reservoir of GABAergic interneurons not only for the OB, but also for other cortical and subcortical areas.}, Author = {Inta, Dragos and Alfonso, Julieta and von Engelhardt, Jakob and Kreuzberg, Maria M and Meyer, Axel H and van Hooft, Johannes A and Monyer, Hannah}, Date-Added = {2012-02-24 16:43:09 -0500}, Date-Modified = {2012-02-24 16:43:49 -0500}, Doi = {10.1073/pnas.0807059105}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Adult Neurogenesis; Neocortex; neuron; mouse; brdu}, Mesh = {Animals; Animals, Newborn; Cell Movement; Mice; Mice, Transgenic; Neurogenesis; Neurons; Prosencephalon; Serotonin; gamma-Aminobutyric Acid}, Month = {Dec}, Number = {52}, Pages = {20994-9}, Pmc = {PMC2605417}, pmid = {19095802}, Pst = {ppublish}, Title = {Neurogenesis and widespread forebrain migration of distinct GABAergic neurons from the postnatal subventricular zone}, Volume = {105}, Year = {2008}, url = {papers/Inta_ProcNatlAcadSciUSA2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0807059105}} @article{Snyder:2009, Abstract = {Neurons are born throughout adulthood in the hippocampus and show enhanced plasticity compared with mature neurons. However, there are conflicting reports on whether or not young neurons contribute to performance in behavioral tasks, and there is no clear relationship between the timing of maturation of young neurons and the duration of neurogenesis reduction in studies showing behavioral deficits. We asked whether these discrepancies could reflect differences in the properties of young neurons in mice and rats. We report that young neurons in adult rats show a mature neuronal marker profile and activity-induced immediate early gene expression 1-2 weeks earlier than those in mice. They are also twice as likely to escape cell death, and are 10 times more likely to be recruited into learning circuits. This comparison holds true in two different strains of mice, both of which show high rates of neurogenesis relative to other background strains. Differences in adult neurogenesis are not limited to the hippocampus, as the density of new neocortical neurons was 5 times greater in rats than in mice. Finally, in a test of function, we find that the contribution of young neurons to fear memory is much greater in rats than in mice. These results reveal substantial differences in new neuron plasticity and function between these two commonly studied rodent species.}, Author = {Snyder, Jason S and Choe, Jessica S and Clifford, Meredith A and Jeurling, Sara I and Hurley, Patrick and Brown, Ashly and Kamhi, J Frances and Cameron, Heather A}, Date-Added = {2012-02-24 16:40:52 -0500}, Date-Modified = {2012-02-24 16:42:06 -0500}, Doi = {10.1523/JNEUROSCI.1768-09.2009}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Adult Neurogenesis; neuron; Neocortex; brdu; mouse; rat; hippocampus}, Mesh = {Aging; Animals; Behavior, Animal; Hippocampus; Male; Mice; Mice, Inbred C57BL; Neurogenesis; Neuronal Plasticity; Neurons; Rats; Rats, Sprague-Dawley; Species Specificity}, Month = {Nov}, Number = {46}, Pages = {14484-95}, Pmc = {PMC2830901}, pmid = {19923282}, Pst = {ppublish}, Title = {Adult-born hippocampal neurons are more numerous, faster maturing, and more involved in behavior in rats than in mice}, Volume = {29}, Year = {2009}, url = {papers/Snyder_JNeurosci2009.pdf}, Bdsk-File-2 = {papers/Snyder_JNeurosci2009a.pdf}} @article{Siegel:2012, Abstract = {Spontaneous network activity constitutes a central theme during the development of neuronal circuitry [1, 2]. Before the onset of vision, retinal neurons generate waves of spontaneous activity that are relayed along the ascending visual pathway [3, 4] and shape activity patterns in these regions [5, 6]. The spatiotemporal nature of retinal waves is required to establish precise functional maps in higher visual areas, and their disruption results in enlarged axonal projection areas (e.g., [7-10]). However, how retinal inputs shape network dynamics in the visual cortex on the cellular level is unknown. Using in vivo two-photon calcium imaging, we identified two independently occurring patterns of network activity in the mouse primary visual cortex (V1) before and at the onset of vision. Acute manipulations of spontaneous retinal activity revealed that one type of network activity largely originated in the retina and was characterized by low synchronicity (L-) events. In addition, we identified a type of high synchronicity (H-) events that required gap junction signaling but were independent of retinal input. Moreover, the patterns differed in wave progression and developmental profile. Our data suggest that different activity patterns have complementary functions during the formation of synaptic circuits in the developing visual cortex.}, Author = {Siegel, Friederike and Heimel, J Alexander and Peters, Judith and Lohmann, Christian}, Date-Added = {2012-02-13 17:41:16 -0500}, Date-Modified = {2013-05-21 19:47:22 +0000}, Doi = {10.1016/j.cub.2011.12.026}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {retinal wave paper; Spontaneous activity; 21 Activity-development; 21 Calcium imaging; 21 Neurophysiology; optical imaging; optical physiology; multiphoton; visual cortex; Mouse; in vivo; currOpinRvw}, Month = {Feb}, Number = {3}, Pages = {253-8}, pmid = {22264606}, Pst = {ppublish}, Title = {Peripheral and central inputs shape network dynamics in the developing visual cortex in vivo}, Volume = {22}, Year = {2012}, url = {papers/Siegel_CurrBiol2012.pdf}, Bdsk-File-2 = {papers/Siegel_CurrBiol2012a.pdf}, Bdsk-File-3 = {papers/Siegel_CurrBiol2012b.pdf}, Bdsk-File-4 = {papers/Siegel_CurrBiol2012.avi}} @article{Breunig:2007a, Abstract = {Adult neurogenesis research has made enormous strides in the last decade but has been complicated by several failures to replicate promising findings. Prevalent use of highly sensitive methods with inherent sources of error has led to extraordinary conclusions without adequate crossvalidation. Perhaps the biggest culprit is the reliance on molecules involved in DNA synthesis and genetic markers to indicate neuronal neogenesis. In this Protocol Review, we present an overview of common methodological issues in the field and suggest alternative approaches, including viral vectors, siRNA, and inducible transgenic/knockout mice. A multipronged approach will enhance the overall rigor of research on stem cell biology and related fields by allowing increased replication of findings between groups and across systems.}, Author = {Breunig, Joshua J and Arellano, Jon I and Macklis, Jeffrey D and Rakic, Pasko}, Date-Added = {2012-02-06 17:52:26 -0500}, Date-Modified = {2012-02-06 17:52:50 -0500}, Doi = {10.1016/j.stem.2007.11.008}, Journal = {Cell Stem Cell}, Journal-Full = {Cell stem cell}, Keywords = {Adult Neurogenesis; Neocortex; development; neuron}, Mesh = {Animals; Bystander Effect; Humans; Nerve Regeneration; Promoter Regions, Genetic; Reproducibility of Results; Staining and Labeling; Stem Cells}, Month = {Dec}, Number = {6}, Pages = {612-27}, pmid = {18371403}, Pst = {ppublish}, Title = {Everything that glitters isn't gold: a critical review of postnatal neural precursor analyses}, Volume = {1}, Year = {2007}, url = {papers/Breunig_CellStemCell2007.pdf}} @article{Fortin:1999, Abstract = {Visually responsive neurons were recorded in the superficial layers of rat superior colliculus from postnatal day 12 to 28. Receptive field properties such as size, type (ON, OFF, ON-OFF and motion sensitive) and direction selectivity were analyzed to disclose changes during maturation. Although some aspects of sensory properties are modified during development (latency, receptive field sizes, and proportions of receptive field types), a high level of sophistication is also present in young animals even before eyelid opening. For instance, direction selective and direction biased cells, which require complex synaptic relations, are already observed when the first light evoked responses emerge in the superior colliculus (P13), strongly suggesting that this property develops without visual experience. Furthermore, direction selectivity is present in the colliculus prior to the appearance of visually evoked activity in the cortex. This indicates that direction selectivity can not be attributable to incoming cortical afferents. This study provides the first direct evidence that, unlike the cat, the rat's cortico-tectal pathway is only weakly involved in the establishment of direction selectivity in collicular neurons.}, Author = {Fortin, S and Chabli, A and Dumont, I and Shumikhina, S and Itaya, S K and Molotchnikoff, S}, Date-Added = {2012-01-30 18:23:12 -0500}, Date-Modified = {2012-01-30 18:27:54 -0500}, Journal = {Brain Res Dev Brain Res}, Journal-Full = {Brain research. Developmental brain research}, Keywords = {Superior Colliculus; optic tectum; function; visual system; Motion Perception; topographic map; development; 21 Activity-development; Spontaneous activity; rat}, Mesh = {Aging; Animals; Animals, Newborn; Brain Mapping; Electrophysiology; Photic Stimulation; Rats; Rats, Long-Evans; Reaction Time; Superior Colliculi; Visual Pathways}, Month = {Jan}, Number = {1}, Pages = {55-64}, pmid = {9974159}, Pst = {ppublish}, Title = {Maturation of visual receptive field properties in the rat superior colliculus}, Volume = {112}, Year = {1999}, url = {papers/Fortin_BrainResDevBrainRes1999.pdf}} @article{Mooney:1985, Abstract = {Intracellular recording, receptive field mapping, and horseradish peroxidase (HRP) injection techniques were used to determine the structural and functional characteristics of neurons in the superficial laminae (stratum griseum superficiale and stratum opticum) of the hamster's superior colliculus (SC). Fifty-nine neurons (from 38 different hamsters) were successfully characterized, injected with HRP, and recovered. Of these, 8 were marginal cells, 14 had stellate morphology, 10 had narrow, vertically oriented dendritic trees, 12 had wide, vertically oriented dendritic arbors, and 8 were horizontal cells. Seven neurons had somatodendritic morphologies which did not fall into any of these groups. Overall, the distribution of receptive field properties for these cells matched that obtained in previous extracellular recordings from the superficial SC laminae in this species (Chalupa, L.M., and R.W. Rhoades (1977) J. Physiol. (Lond.) 270: 595-626; Chalupa, L.M. and R.W. Rhoades (1978) J. Physiol. (Lond.) 274: 571-592). There were significant correlations between receptive field properties and morphology. Sixty-four percent of the stellate cells and 75% of the marginal cells were directionally selective. Only 17% of the other cell types exhibited this response property. In addition, only 36% of the stellate cells and 25% of the marginal neurons were discharged by stationary, flashed spots. Eighty-one percent of the other recovered cells gave reliable responses to such stimuli. Stellate and marginal cells could also be differentiated from the other cell types on the basis of speed selectivity. Only 29% of the stellate and 13% of the marginal cells responded to stimulus speeds in excess of 20 degrees/sec.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Mooney, R D and Klein, B G and Rhoades, R W}, Date-Added = {2012-01-30 15:20:14 -0500}, Date-Modified = {2012-01-30 16:12:47 -0500}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {visual system; Superior Colliculus; optic tectum; intracellular; 21 Neurophysiology; function; topographic map; Motion Perception; Hamsters}, Mesh = {Animals; Cricetinae; Dendrites; Electrophysiology; Horseradish Peroxidase; Membrane Potentials; Neurons; Superior Colliculi}, Month = {Nov}, Number = {11}, Pages = {2989-3009}, pmid = {4056863}, Pst = {ppublish}, Title = {Correlations between the structural and functional characteristics of neurons in the superficial laminae and the hamster's superior colliculus}, Volume = {5}, Year = {1985}} @article{Lo:2011, Abstract = {Neurotropic viruses that conditionally infect or replicate in molecularly defined neuronal subpopulations, and then spread transsynaptically, are powerful tools for mapping neural pathways. Genetically targetable retrograde transsynaptic tracer viruses are available to map the inputs to specific neuronal subpopulations, but an analogous tool for mapping synaptic outputs is not yet available. Here we describe a Cre recombinase-dependent, anterograde transneuronal tracer, based on the H129 strain of herpes simplex virus (HSV). Application of this virus to transgenic or knockin mice expressing Cre in peripheral neurons of the olfactory epithelium or the retina reveals widespread, polysynaptic labeling of higher-order neurons in the olfactory and visual systems, respectively. Polysynaptic pathways were also labeled from cerebellar Purkinje cells. In each system, the pattern of labeling was consistent with classical circuit-tracing studies, restricted to neurons, and anterograde specific. These data provide proof-of-principle for a conditional, nondiluting anterograde transsynaptic tracer for mapping synaptic outputs from genetically marked neuronal subpopulations.}, Author = {Lo, Liching and Anderson, David J}, Date-Added = {2012-01-27 17:41:07 -0500}, Date-Modified = {2012-01-27 17:41:47 -0500}, Doi = {10.1016/j.neuron.2011.12.002}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {ideas; Grants; gene; Mouse; tracer; anterograde tracing; viral gene transfer; connectivity; synapses; Trans-synaptic}, Month = {Dec}, Number = {6}, Pages = {938-50}, pmid = {22196330}, Pst = {ppublish}, Title = {A cre-dependent, anterograde transsynaptic viral tracer for mapping output pathways of genetically marked neurons}, Volume = {72}, Year = {2011}, url = {papers/Lo_Neuron2011.pdf}} @article{Kleindienst:2011, Abstract = {During brain development, before sensory systems become functional, neuronal networks spontaneously generate repetitive bursts of neuronal activity, which are typically synchronized across many neurons. Such activity patterns have been described on the level of networks and cells, but the fine-structure of inputs received by an individual neuron during spontaneous network activity has not been studied. Here, we used calcium imaging to record activity at many synapses of hippocampal pyramidal neurons simultaneously to establish the activity patterns in the majority of synapses of an entire cell. Analysis of the spatiotemporal patterns of synaptic activity revealed a fine-scale connectivity rule: neighboring synapses (<16 μm intersynapse distance) are more likely to be coactive than synapses that are farther away from each other. Blocking spiking activity or NMDA receptor activation revealed that the clustering of synaptic inputs required neuronal activity, demonstrating a role of developmentally expressed spontaneous activity for connecting neurons with subcellular precision.}, Author = {Kleindienst, Thomas and Winnubst, Johan and Roth-Alpermann, Claudia and Bonhoeffer, Tobias and Lohmann, Christian}, Date-Added = {2012-01-27 17:39:30 -0500}, Date-Modified = {2012-01-27 17:40:37 -0500}, Doi = {10.1016/j.neuron.2011.10.015}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology; synapse formation; Neurotransmitter; hippocampus; calcium imaging; in vitro; connectivity; development}, Month = {Dec}, Number = {6}, Pages = {1012-24}, pmid = {22196336}, Pst = {ppublish}, Title = {Activity-dependent clustering of functional synaptic inputs on developing hippocampal dendrites}, Volume = {72}, Year = {2011}, url = {papers/Kleindienst_Neuron2011.pdf}} @article{Marshel:2011, Abstract = {To establish the mouse as a genetically tractable model for high-order visual processing, we characterized fine-scale retinotopic organization of visual cortex and determined functional specialization of layer 2/3 neuronal populations in seven retinotopically identified areas. Each area contains a distinct visuotopic representation and encodes a unique combination of spatiotemporal features. Areas LM, AL, RL, and AM prefer up to three times faster temporal frequencies and significantly lower spatial frequencies than V1, while V1 and PM prefer high spatial and low temporal frequencies. LI prefers both high spatial and temporal frequencies. All extrastriate areas except LI increase orientation selectivity compared to V1, and three areas are significantly more direction selective (AL, RL, and AM). Specific combinations of spatiotemporal representations further distinguish areas. These results reveal that mouse higher visual areas are functionally distinct, and separate groups of areas may be specialized for motion-related versus pattern-related computations, perhaps forming pathways analogous to dorsal and ventral streams in other species.}, Author = {Marshel, James H and Garrett, Marina E and Nauhaus, Ian and Callaway, Edward M}, Date-Added = {2012-01-27 17:38:13 -0500}, Date-Modified = {2012-01-27 17:38:49 -0500}, Doi = {10.1016/j.neuron.2011.12.004}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Neurophysiology; topographic map; Orientation; visual system; mouse; visual cortex; in vivo; optical physiology; optical imaging; calcium imaging; multiphoton; microscopy; intrinsic signal}, Month = {Dec}, Number = {6}, Pages = {1040-54}, Pmc = {PMC3248795}, pmid = {22196338}, Pst = {ppublish}, Title = {Functional specialization of seven mouse visual cortical areas}, Volume = {72}, Year = {2011}, url = {papers/Marshel_Neuron2011.pdf}} @article{Andermann:2011, Abstract = {The mouse is emerging as an important model for understanding how sensory neocortex extracts cues to guide behavior, yet little is known about how these cues are processed beyond primary cortical areas. Here, we used two-photon calcium imaging in awake mice to compare visual responses in primary visual cortex (V1) and in two downstream target areas, AL and PM. Neighboring V1 neurons had diverse stimulus preferences spanning five octaves in spatial and temporal frequency. By contrast, AL and PM neurons responded best to distinct ranges of stimulus parameters. Most strikingly, AL neurons preferred fast-moving stimuli while PM neurons preferred slow-moving stimuli. By contrast, neurons in V1, AL, and PM demonstrated similar selectivity for stimulus orientation but not for stimulus direction. Based on these findings, we predict that area AL helps guide behaviors involving fast-moving stimuli (e.g., optic flow), while area PM helps guide behaviors involving slow-moving objects.}, Author = {Andermann, Mark L and Kerlin, Aaron M and Roumis, Demetris K and Glickfeld, Lindsey L and Reid, R Clay}, Date-Added = {2012-01-27 17:35:48 -0500}, Date-Modified = {2012-01-27 17:38:37 -0500}, Doi = {10.1016/j.neuron.2011.11.013}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Neurophysiology; topographic map; Orientation; visual system; mouse; visual cortex; in vivo; optical physiology; optical imaging; calcium imaging; multiphoton; microscopy;}, Month = {Dec}, Number = {6}, Pages = {1025-39}, pmid = {22196337}, Pst = {ppublish}, Title = {Functional specialization of mouse higher visual cortical areas}, Volume = {72}, Year = {2011}, url = {papers/Andermann_Neuron2011.pdf}, Bdsk-File-2 = {papers/Andermann_Neuron2011a.pdf}, Bdsk-File-3 = {papers/Andermann_Neuron2011b.pdf}} @article{Kim:2011, Abstract = {The GFP reconstitution across synaptic partners (GRASP) technique, based on functional complementation between two nonfluorescent GFP fragments, can be used to detect the location of synapses quickly, accurately and with high spatial resolution. The method has been previously applied in the nematode and the fruit fly but requires substantial modification for use in the mammalian brain. We developed mammalian GRASP (mGRASP) by optimizing transmembrane split-GFP carriers for mammalian synapses. Using in silico protein design, we engineered chimeric synaptic mGRASP fragments that were efficiently delivered to synaptic locations and reconstituted GFP fluorescence in vivo. Furthermore, by integrating molecular and cellular approaches with a computational strategy for the three-dimensional reconstruction of neurons, we applied mGRASP to both long-range circuits and local microcircuits in the mouse hippocampus and thalamocortical regions, analyzing synaptic distribution in single neurons and in dendritic compartments.}, Author = {Kim, Jinhyun and Zhao, Ting and Petralia, Ronald S and Yu, Yang and Peng, Hanchuan and Myers, Eugene and Magee, Jeffrey C}, Date-Added = {2012-01-27 17:34:23 -0500}, Date-Modified = {2012-01-27 17:35:08 -0500}, Doi = {10.1038/nmeth.1784}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {synapses; microscopy; gene; technique; ideas; mouse; hippocampus; connectivity; connectome}, Number = {1}, Pages = {96-102}, pmid = {22138823}, Pst = {epublish}, Title = {mGRASP enables mapping mammalian synaptic connectivity with light microscopy}, Volume = {9}, Year = {2011}, url = {papers/Kim_NatMethods2011.pdf}} @article{Kralj:2011a, Abstract = {Reliable optical detection of single action potentials in mammalian neurons has been one of the longest-standing challenges in neuroscience. Here we achieved this goal by using the endogenous fluorescence of a microbial rhodopsin protein, Archaerhodopsin 3 (Arch) from Halorubrum sodomense, expressed in cultured rat hippocampal neurons. This genetically encoded voltage indicator exhibited an approximately tenfold improvement in sensitivity and speed over existing protein-based voltage indicators, with a roughly linear twofold increase in brightness between -150 mV and +150 mV and a sub-millisecond response time. Arch detected single electrically triggered action potentials with an optical signal-to-noise ratio >10. Arch(D95N) lacked endogenous proton pumping and had 50% greater sensitivity than wild type but had a slower response (41 ms). Nonetheless, Arch(D95N) also resolved individual action potentials. Microbial rhodopsin-based voltage indicators promise to enable optical interrogation of complex neural circuits and electrophysiology in systems for which electrode-based techniques are challenging.}, Author = {Kralj, Joel M and Douglass, Adam D and Hochbaum, Daniel R and Maclaurin, Dougal and Cohen, Adam E}, Date-Added = {2012-01-27 17:32:45 -0500}, Date-Modified = {2012-01-27 17:33:50 -0500}, Doi = {10.1038/nmeth.1782}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology; optical imaging; voltage sensor; in vitro; hippocampus; rat; Technique; gene}, Number = {1}, Pages = {90-5}, Pmc = {PMC3248630}, pmid = {22120467}, Pst = {epublish}, Title = {Optical recording of action potentials in mammalian neurons using a microbial rhodopsin}, Volume = {9}, Year = {2011}, url = {papers/Kralj_NatMethods2011.pdf}, Bdsk-File-2 = {papers/Kralj_NatMethods2011a.pdf}, Bdsk-File-3 = {papers/Kralj_NatMethods2011b.pdf}} @article{Ji:2012, Abstract = {The signal and resolution during in vivo imaging of the mouse brain is limited by sample-induced optical aberrations. We find that, although the optical aberrations can vary across the sample and increase in magnitude with depth, they remain stable for hours. As a result, two-photon adaptive optics can recover diffraction-limited performance to depths of 450 μm and improve imaging quality over fields of view of hundreds of microns. Adaptive optical correction yielded fivefold signal enhancement for small neuronal structures and a threefold increase in axial resolution. The corrections allowed us to detect smaller neuronal structures at greater contrast and also improve the signal-to-noise ratio during functional Ca(2+) imaging in single neurons.}, Author = {Ji, Na and Sato, Takashi R and Betzig, Eric}, Date-Added = {2012-01-27 17:31:06 -0500}, Date-Modified = {2012-01-27 17:31:34 -0500}, Doi = {10.1073/pnas.1109202108}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Technique; in vivo; calcium imaging; Optics; multiphoton}, Month = {Jan}, Number = {1}, Pages = {22-7}, Pmc = {PMC3252919}, pmid = {22190489}, Pst = {ppublish}, Title = {Characterization and adaptive optical correction of aberrations during in vivo imaging in the mouse cortex}, Volume = {109}, Year = {2012}, url = {papers/Ji_ProcNatlAcadSciUSA2012.pdf}} @article{Tolner:2012, Abstract = {Patterned neuronal activity such as spindle bursts in the neonatal cortex is likely to promote the maturation of cortical synapses and neuronal circuits. Previous work on cats has shown that removal of subplate neurons, a transient neuronal population in the immature cortex, prevents the functional maturation of thalamocortical and intracortical connectivity. Here we studied the effect of subplate removal in the neonatal rat primary somatosensory cortex (S1). Using intracortical EEG we show that after selective removal of subplate neurons in the limb region of S1, endogenous and sensory evoked spindle burst activity is largely abolished. Consistent with the reduced in vivo activity in the S1 limb region, we find by in vitro recordings that thalamocortical inputs to layer 4 neurons are weak. In addition, we find that removal of subplate neurons in the S1 barrel region prevents the development of the characteristic histological barrel-like appearance. Thus, subplate neurons are crucially involved in the generation of particular types of early network activity in the neonatal cortex, which are an important feature of cortical development. The altered EEG pattern following subplate damage could be applicable in the neurological assessment of human neonates.}, Author = {Tolner, Else A and Sheikh, Aminah and Yukin, Alexey Y and Kaila, Kai and Kanold, Patrick O}, Date-Added = {2012-01-27 17:28:33 -0500}, Date-Modified = {2012-01-27 17:29:33 -0500}, Doi = {10.1523/JNEUROSCI.1538-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; development; 21 Neurophysiology; in vivo; extracellular; Somatosensory Cortex; rat; Spontaneous activity; neonatal}, Month = {Jan}, Number = {2}, Pages = {692-702}, pmid = {22238105}, Pst = {ppublish}, Title = {Subplate neurons promote spindle bursts and thalamocortical patterning in the neonatal rat somatosensory cortex}, Volume = {32}, Year = {2012}, url = {papers/Tolner_JNeurosci2012.pdf}} @article{Podgorski:2012, Abstract = {Sensory experience drives dramatic structural and functional plasticity in developing neurons. However, for single-neuron plasticity to optimally improve whole-network encoding of sensory information, changes must be coordinated between neurons to ensure a full range of stimuli is efficiently represented. Using two-photon calcium imaging to monitor evoked activity in over 100 neurons simultaneously, we investigate network-level changes in the developing Xenopus laevis tectum during visual training with motion stimuli. Training causes stimulus-specific changes in neuronal responses and interactions, resulting in improved population encoding. This plasticity is spatially structured, increasing tuning curve similarity and interactions among nearby neurons, and decreasing interactions among distant neurons. Training does not improve encoding by single clusters of similarly responding neurons, but improves encoding across clusters, indicating coordinated plasticity across the network. NMDA receptor blockade prevents coordinated plasticity, reduces clustering, and abolishes whole-network encoding improvement. We conclude that NMDA receptors support experience-dependent network self-organization, allowing efficient population coding of a diverse range of stimuli.}, Author = {Podgorski, Kaspar and Dunfield, Derek and Haas, Kurt}, Date-Added = {2012-01-27 17:25:51 -0500}, Date-Modified = {2012-01-27 17:27:12 -0500}, Doi = {10.1371/journal.pbio.1001236}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {development; retinal; visual system; optic tectum; Xenopus; calcium imaging; in vivo; 21 Activity-development; 21 Neurophysiology; topographic map; Orientation; Learning; plasticity}, Month = {Jan}, Number = {1}, Pages = {e1001236}, Pmc = {PMC3254648}, pmid = {22253571}, Pst = {ppublish}, Title = {Functional Clustering Drives Encoding Improvement in a Developing Brain Network during Awake Visual Learning}, Volume = {10}, Year = {2012}, url = {papers/Podgorski_PLoSBiol2012.pdf}} @article{Wu:2012, Abstract = {Accumulating evidence indicates that GABA acts beyond inhibitory synaptic transmission and regulates the development of inhibitory synapses in the vertebrate brain, but the underlying cellular mechanism is not well understood. We have combined live imaging of cortical GABAergic axons across time scales from minutes to days with single-cell genetic manipulation of GABA release to examine its role in distinct steps of inhibitory synapse formation in the mouse neocortex. We have shown previously, by genetic knockdown of GABA synthesis in developing interneurons, that GABA signaling promotes the maturation of inhibitory synapses and axons. Here we found that a complete blockade of GABA release in basket interneurons resulted in an opposite effect, a cell-autonomous increase in axon and bouton density with apparently normal synapse structures. These results not only demonstrate that GABA is unnecessary for synapse formation per se but also uncover a novel facet of GABA in regulating synapse elimination and axon pruning. Live imaging revealed that developing GABAergic axons form a large number of transient boutons, but only a subset was stabilized. Release blockade led to significantly increased bouton stability and filopodia density, increased axon branch extension, and decreased branch retraction. Our results suggest that a major component of GABA function in synapse development is transmission-mediated elimination of subsets of nascent contacts. Therefore, GABA may regulate activity-dependent inhibitory synapse formation by coordinately eliminating certain nascent contacts while promoting the maturation of other nascent synapses.}, Author = {Wu, Xiaoyun and Fu, Yu and Knott, Graham and Lu, Jiangteng and Di Cristo, Graziella and Huang, Z Josh}, Date-Added = {2012-01-27 17:22:58 -0500}, Date-Modified = {2012-01-27 17:24:46 -0500}, Doi = {10.1523/JNEUROSCI.3189-11.2012}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; axon guidance; connectivity; refinement; plasticity; GABA; mouse; Neurotransmitter; synapse formation}, Month = {Jan}, Number = {1}, Pages = {331-43}, pmid = {22219294}, Pst = {ppublish}, Title = {GABA Signaling Promotes Synapse Elimination and Axon Pruning in Developing Cortical Inhibitory Interneurons}, Volume = {32}, Year = {2012}, url = {papers/Wu_JNeurosci2012.pdf}} @article{Cossart:2011, Abstract = {If the classical functional attribute of cortical GABAergic interneurons is to mediate synaptic inhibition in the adult cortex, it is becoming evident that their major task is instead to shape the spatio-temporal dynamics of the network oscillations that support most brain functions. This complex function involves a division of labour between morpho-physiologically diverse interneuron subtypes. Both the central network function and the bewildering heterogeneity of the interneuron population are especially emphasized during cortical development: at early postnatal stages, a single GABAergic neuron can efficiently pace the activity of hundreds of other cells, whereas some interneuron subtypes are still poorly developed. Given the role of coherent activity in brain development, this confers to GABAergic interneurons a major role in the proper maturation of cortical networks.}, Author = {Cossart, Rosa}, Date-Added = {2012-01-27 17:15:39 -0500}, Date-Modified = {2013-05-21 19:47:22 +0000}, Doi = {10.1016/j.conb.2010.10.003}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {GABA; interneurons; connectivity; network; calcium imaging; review; hippocampus; currOpinRvw}, Mesh = {Animals; Cerebral Cortex; Humans; Interneurons; Neural Pathways; Neurogenesis}, Month = {Feb}, Number = {1}, Pages = {160-8}, pmid = {21074988}, Pst = {ppublish}, Title = {The maturation of cortical interneuron diversity: how multiple developmental journeys shape the emergence of proper network function}, Volume = {21}, Year = {2011}, url = {papers/Cossart_CurrOpinNeurobiol2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2010.10.003}} @article{Feldt:2011, Abstract = {Structure-function studies of neuronal networks have recently benefited from considerable progress in different areas of investigation. Advances in molecular genetics and imaging have allowed for the dissection of neuronal connectivity with unprecedented detail whereas in vivo recordings are providing much needed clues as to how sensory, motor and cognitive function is encoded in neuronal firing. However, bridging the gap between the cellular and behavioral levels will ultimately require an understanding of the functional organization of the underlying neuronal circuits. One way to unravel the complexity of neuronal networks is to understand how their connectivity emerges during brain maturation. In this review, we will describe how graph theory provides experimentalists with novel concepts that can be used to describe and interpret these developing connectivity schemes.}, Author = {Feldt, Sarah and Bonifazi, Paolo and Cossart, Rosa}, Date-Added = {2012-01-27 17:13:57 -0500}, Date-Modified = {2012-01-27 17:15:03 -0500}, Doi = {10.1016/j.tins.2011.02.007}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {21 Calcium imaging; 21 Activity-development; 21 Neurophysiology; connectivity; connectome; network; review; development}, Mesh = {Action Potentials; Animals; Computer Simulation; Humans; Models, Anatomic; Models, Neurological; Nerve Net; Neurons}, Month = {May}, Number = {5}, Pages = {225-36}, pmid = {21459463}, Pst = {ppublish}, Title = {Dissecting functional connectivity of neuronal microcircuits: experimental and theoretical insights}, Volume = {34}, Year = {2011}, url = {papers/Feldt_TrendsNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2011.02.007}} @article{Picardo:2011, Abstract = {Connectivity in the developing hippocampus displays a functional organization particularly effective in supporting network synchronization, as it includes superconnected hub neurons. We have previously shown that hub network function is supported by a subpopulation of GABA neurons. However, it is unclear whether hub cells are only transiently present or later develop into distinctive subclasses of interneurons. These questions are difficult to assess given the heterogeneity of the GABA neurons and the poor early expression of markers. To circumvent this conundrum, we used "genetic fate mapping" that allows for the selective labeling of GABA neurons based on their place and time of origin. We show that early-generated GABA cells form a subpopulation of hub neurons, characterized by an exceptionally widespread axonal arborization and the ability to single-handedly impact network dynamics when stimulated. Pioneer hub neurons remain into adulthood, when they acquire the classical markers of long-range projecting GABA neurons.}, Author = {Picardo, Michel Aim{\'e} and Guigue, Philippe and Bonifazi, Paolo and Batista-Brito, Renata and Allene, Camille and Ribas, Alain and Fishell, Gord and Baude, Agn{\`e}s and Cossart, Rosa}, Date-Added = {2012-01-27 17:10:55 -0500}, Date-Modified = {2012-01-27 17:13:04 -0500}, Doi = {10.1016/j.neuron.2011.06.018}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology; hippocampus; Mouse; GABA; interneurons; connectivity; connectome; Patch-Clamp Techniques; calcium imaging}, Mesh = {Action Potentials; Animals; Axons; Cell Lineage; Female; Hippocampus; Interneurons; Male; Mice; Mice, Transgenic; Neurogenesis; Neurons; Patch-Clamp Techniques; gamma-Aminobutyric Acid}, Month = {Aug}, Number = {4}, Pages = {695-709}, Pmc = {PMC3163067}, pmid = {21867885}, Pst = {ppublish}, Title = {Pioneer GABA cells comprise a subpopulation of hub neurons in the developing hippocampus}, Volume = {71}, Year = {2011}, url = {papers/Picardo_Neuron2011.pdf}, Bdsk-File-2 = {papers/Picardo_Neuron2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.06.018}} @article{Chapman:1986, Abstract = {Monocular lid suture during the sensitive period early in the life of a kitten disrupts normal development of inputs from the two eyes to the visual cortex, causing a decrease in the fraction of cortical cells responding to the deprived eye. Such an ocular dominance shift has been assumed to depend on patterned visual experience, because no change in cortical physiology is produced by inequalities between the two eyes in retinal illumination or temporally modulated diffuse light stimulation. A higher-level process, involving gating signals from areas outside striate cortex, has been proposed to ensure that sustained changes in synaptic efficacy occur only in response to behaviourally significant visual inputs. To test whether such a process is necessary for ocular dominance plasticity, we treated 4-week-old kittens with visual deprivation and monocular tetrodotoxin (TTX) injections to create an imbalance in the electrical activities of the two retinas in the absence of patterned vision. After 1 week of treatment we determined the ocular dominance distribution of single units in primary visual cortex. In all kittens studied, a significant ocular dominance shift was found. In addition to this physiological change, there was an anatomical change in the lateral geniculate nucleus, where cells were larger in laminae receiving input from the more active eye. Our results indicate that patterned vision is not necessary for visual cortical plasticity, and that an imbalance in spontaneous retinal activity alone can produce a significant ocular dominance shift.}, Author = {Chapman, B and Jacobson, M D and Reiter, H O and Stryker, M P}, Date = {1986 Nov 13-19}, Date-Added = {2012-01-18 11:08:08 -0500}, Date-Modified = {2012-01-18 11:09:00 -0500}, Doi = {10.1038/324154a0}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {retinal wave paper; Spontaneous activity; 21 Activity-development; 21 Neurophysiology; Tetrodotoxin; cat; visual cortex; topographic map; hebbian; Competitive Behavior; Binocular}, Mesh = {Animals; Cats; Electrophysiology; Geniculate Bodies; Neuronal Plasticity; Retina; Tetrodotoxin; Vision, Ocular; Visual Cortex; Visual Pathways}, Number = {6093}, Pages = {154-6}, pmid = {3785380}, Pst = {ppublish}, Title = {Ocular dominance shift in kitten visual cortex caused by imbalance in retinal electrical activity}, Volume = {324}, Year = {1986}, url = {papers/Chapman_Nature1986.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/324154a0}} @article{Yamashita:2003, Abstract = {Cortical inhibition is determined in part by the organization of synaptic inputs to gamma-aminobutyric acidergic (GABAergic) neurons. In adult rat visual cortex, feedforward (FF) and feedback (FB) connections that link lower with higher areas provide approximately 10% of inputs to parvalbumin (PV)-expressing GABAergic neurons and approximately 90% to non-GABAergic cells (Gonchar and Burkhalter [1999] J. Comp. Neurol. 406:346-360). Although the proportions of these targets are similar in both pathways, FF synapses prefer larger PV dendrites than FB synapses, which may result in stronger inhibition in the FF than in the FB pathway (Gonchar and Burkhalter [1999] J. Comp. Neurol. 406:346-360). To determine when during postnatal (P) development FF and FB inputs to PV and non-PV neurons acquire mature proportions, and whether the pathway-specific distributions of FF and FB inputs to PV dendrites develop from a similar pattern, we studied FF and FB connections between area 17 and the higher order lateromedial area (LM) in visual cortex of P15-42 mice. We found that the innervation ratio of PV and non-PV neurons is mature at P15. Furthermore, the size distributions of PV dendrites contacted by FF and FB synapses were similar at P15 but changed during the third to sixth postnatal weeks so that, by P36-42, FF inputs preferred thick dendrites and FB synapses favored thin PV dendrites. These results suggest that distinct FF and FB circuits develop after eye opening by rearranging the distribution of excitatory synaptic inputs on the dendritic tree of PV neurons. The purpose of this transformation may be to adjust differentially the strengths of inhibition in FF and FB circuits.}, Author = {Yamashita, Akiko and Valkova, Katia and Gonchar, Yuri and Burkhalter, Andreas}, Date-Added = {2012-01-17 14:19:11 -0500}, Date-Modified = {2012-01-17 14:19:26 -0500}, Doi = {10.1002/cne.10810}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {mouse; visual cortex; topographic map; 21 Neurophysiology; 21 Circuit structure-function; in vivo;}, Mesh = {Aging; Animals; Animals, Newborn; Axons; Cell Aging; Dendrites; Feedback; Mice; Mice, Inbred C57BL; Neural Inhibition; Neural Pathways; Neurons; Parvalbumins; Synapses; Visual Cortex}, Month = {Sep}, Number = {4}, Pages = {426-37}, pmid = {12900914}, Pst = {ppublish}, Title = {Rearrangement of synaptic connections with inhibitory neurons in developing mouse visual cortex}, Volume = {464}, Year = {2003}, url = {papers/Yamashita_JCompNeurol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10810}} @article{Wang:2011a, Abstract = {It is widely held that the spatial processing functions underlying rodent navigation are similar to those encoding human episodic memory (Doeller et al., 2010). Spatial and nonspatial information are provided by all senses including vision. It has been suggested that visual inputs are fed to the navigational network in cortex and hippocampus through dorsal and ventral intracortical streams (Whitlock et al., 2008), but this has not been shown directly in rodents. We have used cytoarchitectonic and chemoarchitectonic markers, topographic mapping of receptive fields, and pathway tracing to determine in mouse visual cortex whether the lateromedial field (LM) and the anterolateral field (AL), which are the principal targets of primary visual cortex (V1) (Wang and Burkhalter, 2007) specialized for processing nonspatial and spatial visual information (Gao et al., 2006), are distinct areas with diverse connections. We have found that the LM/AL border coincides with a change in type 2 muscarinic acetylcholine receptor expression in layer 4 and with the representation of the lower visual field periphery. Our quantitative analyses also show that LM strongly projects to temporal cortex as well as the lateral entorhinal cortex, which has weak spatial selectivity (Hargreaves et al., 2005). In contrast, AL has stronger connections with posterior parietal cortex, motor cortex, and the spatially selective medial entorhinal cortex (Haftig et al., 2005). These results support the notion that LM and AL are architecturally, topographically, and connectionally distinct areas of extrastriate visual cortex and that they are gateways for ventral and dorsal streams.}, Author = {Wang, Quanxin and Gao, Enquan and Burkhalter, Andreas}, Date-Added = {2012-01-17 14:13:50 -0500}, Date-Modified = {2012-01-17 14:17:36 -0500}, Doi = {10.1523/JNEUROSCI.3488-10.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {mouse; visual cortex; topographic map; 21 Neurophysiology; 21 Circuit structure-function; in vivo; microscopy}, Mesh = {Animals; Bisbenzimidazole; Entorhinal Cortex; Female; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Microinjections; Motor Cortex; Neural Pathways; Parietal Lobe; Receptor, Muscarinic M2; Temporal Lobe; Visual Cortex}, Month = {Feb}, Number = {5}, Pages = {1905-18}, Pmc = {PMC3040111}, pmid = {21289200}, Pst = {ppublish}, Title = {Gateways of ventral and dorsal streams in mouse visual cortex}, Volume = {31}, Year = {2011}, url = {papers/Wang_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3488-10.2011}} @article{Wang:2007c, Abstract = {It is controversial whether mouse extrastriate cortex has a "simple" organization in which lateral primary visual cortex (V1) is adjoined by a single area V2 or has a "complex" organization, in which lateral V1 is adjoined by multiple distinct areas, all of which share the vertical meridian with V1. Resolving this issue is important for understanding the evolution and development of cortical arealization. We have used triple pathway tracing combined with receptive field recordings to map azimuth and elevation in the same brain and have referenced these maps against callosal landmarks. We found that V1 projects to 15 cortical fields. At least nine of these contain maps with complete and orderly representations of the entire visual hemifield and therefore represent distinct areas. One of these, PM, adjoins V1 at the medial border. Five areas, P, LM, AL, RL, and A, adjoin V1 on the lateral border, but only LM shares the vertical meridian representation with V1. This suggests that LM is homologous to V2 and that the lateral extrastriate areas do not represent modules within a single area V2. Thus, mouse visual cortex is "simple" in the sense that lateral V1 is adjoined by a single V2-like area, LM, and "complex" in having a string of areas in lateral extrastriate cortex, which receive direct V1 input. The results suggest that large numbers of areas with topologically equivalent maps of the visual field emerge early in evolution and that homologous areas are inherited in different mammalian lineages.}, Author = {Wang, Quanxin and Burkhalter, Andreas}, Date-Added = {2012-01-17 14:13:48 -0500}, Date-Modified = {2012-01-17 14:17:28 -0500}, Doi = {10.1002/cne.21286}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {mouse; visual cortex; topographic map; 21 Neurophysiology; 21 Circuit structure-function; in vivo; microscopy}, Mesh = {Analysis of Variance; Animals; Biotin; Brain Mapping; Carbocyanines; Dextrans; Evoked Potentials, Visual; Mice; Mice, Inbred C57BL; Microelectrodes; Models, Anatomic; Photic Stimulation; Stereotaxic Techniques; Visual Cortex; Visual Fields; Visual Pathways}, Month = {May}, Number = {3}, Pages = {339-57}, pmid = {17366604}, Pst = {ppublish}, Title = {Area map of mouse visual cortex}, Volume = {502}, Year = {2007}, url = {papers/Wang_JCompNeurol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21286}} @article{Wang:2007b, Abstract = {From the moment the mouse model took center stage for studies of cortical arealization and map formation, there was an urgent need for methods to identify areal borders in the living animal. The need was met in part by intrinsic optical signal imaging, which has been successfully applied to map topographic representations in primary visual, auditory and somatosensory cortex. However, the challenge remains to register these maps to the underlying structure. This is especially important for studies of the mouse brain in which cortical areas are often only a few hundred microns across. Here, we show that in visual cortex neuronal tracing with fluororuby and fluoroemerald can be used for transcranial imaging through the intact skull of callosal connections from the opposite side of the brain, and for mapping of topographic striate-extrastriate cortical pathways in living mice. Because callosal connections are important landmarks for cortical areas, the new method will allow registration of functional maps to underlying structures and facilitate targeted single-unit recordings in identified cortical areas.}, Author = {Wang, Quanxin and Gao, Enquan and Burkhalter, Andreas}, Date-Added = {2012-01-17 14:13:46 -0500}, Date-Modified = {2012-01-17 14:17:22 -0500}, Doi = {10.1016/j.jneumeth.2006.07.024}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {mouse; visual cortex; topographic map; 21 Neurophysiology; 21 Circuit structure-function; in vivo; microscopy}, Mesh = {Animals; Bisbenzimidazole; Brain Mapping; Corpus Callosum; Dextrans; Electrophysiology; Evoked Potentials, Visual; Fluoresceins; Fluorescent Dyes; Mice; Mice, Inbred C57BL; Photic Stimulation; Rhodamines; Stereotaxic Techniques; Visual Cortex; Visual Pathways}, Month = {Jan}, Number = {2}, Pages = {268-76}, pmid = {16945423}, Pst = {ppublish}, Title = {In vivo transcranial imaging of connections in mouse visual cortex}, Volume = {159}, Year = {2007}, url = {papers/Wang_JNeurosciMethods2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2006.07.024}} @article{Dhande:2011a, Abstract = {The targeting and refinement of RGC projections to the midbrain is a popular and powerful model system for studying how precise patterns of neural connectivity form during development. In mice, retinofugal projections are arranged in a topographic manner and form eye-specific layers in the Lateral Geniculate Nucleus (dLGN) of the thalamus and the Superior Colliculus (SC). The development of these precise patterns of retinofugal projections has typically been studied by labeling populations of RGCs with fluorescent dyes and tracers, such as horseradish peroxidase. However, these methods are too coarse to provide insight into developmental changes in individual RGC axonal arbor morphology that are the basis of retinotopic map formation. They also do not allow for the genetic manipulation of RGCs. Recently, electroporation has become an effective method for providing precise spatial and temporal control for delivery of charged molecules into the retina. Current retinal electroporation protocols do not allow for genetic manipulation and tracing of retinofugal projections of a single or small cluster of RGCs in postnatal mice. It has been argued that postnatal in vivo electroporation is not a viable method for transfecting RGCs since the labeling efficiency is extremely low and hence requires targeting at embryonic ages when RGC progenitors are undergoing differentiation and proliferation. In this video we describe an in vivo electroporation protocol for targeted delivery of genes, shRNA, and fluorescent dextrans to murine RGCs postnatally. This technique provides a cost effective, fast and relatively easy platform for efficient screening of candidate genes involved in several aspects of neural development including axon retraction, branching, lamination, regeneration and synapse formation at various stages of circuit development. In summary we describe here a valuable tool which will provide further insights into the molecular mechanisms underlying sensory map development.}, Author = {Dhande, Onkar S and Crair, Michael C}, Date-Added = {2011-12-30 18:33:13 -0500}, Date-Modified = {2011-12-30 18:34:00 -0500}, Doi = {10.3791/2678}, Journal = {J Vis Exp}, Journal-Full = {Journal of visualized experiments : JoVE}, Keywords = {retina; Retinal Ganglion Cells; Electroporation; Technique;}, Mesh = {Animals; Electroporation; Mice; Retinal Ganglion Cells; Transfection}, Number = {50}, pmid = {21525846}, Pst = {epublish}, Title = {Transfection of mouse retinal ganglion cells by in vivo electroporation}, Year = {2011}, Bdsk-Url-1 = {http://dx.doi.org/10.3791/2678}} @article{Zhang:2011, Abstract = {Binocular competition is thought to drive eye-specific segregation in the developing visual system, potentially through Hebbian synaptic learning rules that are sensitive to correlations in afferent activity. Altering retinal activity can disrupt eye-specific segregation, but little is known about the temporal features of binocular activity that modulate visual map development. We used optogenetic techniques to directly manipulate retinal activity in vivo and identified a critical period before eye opening in mice when specific binocular features of retinal activity drive visual map development. Synchronous activation of both eyes disrupted segregation, whereas asynchronous stimulation enhanced segregation. The optogenetic stimulus applied was spatially homogenous; accordingly, retinotopy of ipsilateral projections was markedly perturbed, but contralateral retinotopy was unaffected or even improved. These results provide direct evidence that the synchrony and precise temporal pattern of binocular retinal activity during a critical period in development regulates eye-specific segregation and retinotopy in the developing visual system.}, Author = {Zhang, Jiayi and Ackman, James B and Xu, Hong-Ping and Crair, Michael C}, Date-Added = {2011-12-30 18:04:30 -0500}, Date-Modified = {2013-05-21 19:47:22 +0000}, Doi = {10.1038/nn.3007}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {currOpinRvw}, Month = {Nov}, Number = {2}, Pages = {298-307}, Pmc = {PMC3267873}, pmid = {22179110}, Pst = {aheadofprint}, Title = {Visual map development depends on the temporal pattern of binocular activity in mice}, Volume = {15}, Year = {2011}, url = {papers/Zhang_NatNeurosci2011.pdf}} @book{Gonzalez:2009, Annote = {LDR 01098cam 2200301 a 4500 001 16226866 005 20111011114946.0 008 100511s2009 xx a b 001 0 eng 906 $a7$bcbc$corigres$d2$encip$f20$gy-gencatlg 925 0 $aacquire$b2 shelf copies$xpolicy default 955 $bxh15 2010-05-11 z-processor to xh00$axh00 2010-05-12 to USPL/STM$ixh12 2011-10-11 to OSI 010 $a 2009902793 020 $a9780982085400 020 $a0982085400 040 $aDLC$cDLC 042 $apcc 050 00 $aTA1637$b.G66 2009 100 1 $aGonzalez, Rafael C. 245 10 $aDigital Image processing using MATLAB /$cRafael C. Gonzalez, Richard E. Woods, Steven L. Eddins. 250 $a2nd ed. 260 $a[S.I.] :$bGatesmark Pub.,$cc2009. 300 $axviii, 826 p. :$bill. (some col.) ;$c25 cm. 504 $aIncludes bibliographical references (p. 813-816) and index. 650 0 $aImage processing$xDigital techniques. 650 0 $aImage processing$xMathematics. 630 00 $aMATLAB. 700 1 $aWoods, Richard E.$q(Richard Eugene),$d1954- 700 1 $aEddins, Steven L.,$d1964- }, Author = {Gonzalez, Rafael C and Woods, Richard E and Eddins, Steven L.}, Call-Number = {TA1637}, Date-Added = {2011-12-30 12:42:13 -0500}, Date-Modified = {2011-12-30 12:42:13 -0500}, Edition = {2nd ed}, Genre = {Image processing}, Isbn = {9780982085400}, Library-Id = {2009902793}, Publisher = {Gatesmark Pub.}, Title = {Digital Image processing using MATLAB}, Year = {2009}} @article{Ko:2011, Abstract = {Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.}, Author = {Ko, Ho and Hofer, Sonja B and Pichler, Bruno and Buchanan, Katherine A and Sj{\"o}str{\"o}m, P Jesper and Mrsic-Flogel, Thomas D}, Date-Added = {2011-11-08 09:57:04 -0500}, Date-Modified = {2011-11-08 09:57:48 -0500}, Doi = {10.1038/nature09880}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Activity-development; connectivity; 21 Cortical oscillations; 21 Neurophysiology; Somatosensory Cortex; Mouse; calcium imaging; optical physiology; in vivo}, Mesh = {Animals; Calcium; Calcium Signaling; Computer Simulation; Electrical Synapses; Mice; Mice, Inbred C57BL; Nerve Net; Patch-Clamp Techniques; Photic Stimulation; Pyramidal Cells; Visual Cortex}, Month = {May}, Number = {7345}, Pages = {87-91}, Pmc = {PMC3089591}, pmid = {21478872}, Pst = {ppublish}, Title = {Functional specificity of local synaptic connections in neocortical networks}, Volume = {473}, Year = {2011}, url = {papers/Ko_Nature2011.pdf}, Bdsk-File-2 = {papers/Ko_Nature2011a.pdf}} @article{Kang:2011, Abstract = {Brain development and function depend on the precise regulation of gene expression. However, our understanding of the complexity and dynamics of the transcriptome of the human brain is incomplete. Here we report the generation and analysis of exon-level transcriptome and associated genotyping data, representing males and females of different ethnicities, from multiple brain regions and neocortical areas of developing and adult post-mortem human brains. We found that 86 per cent of the genes analysed were expressed, and that 90 per cent of these were differentially regulated at the whole-transcript or exon level across brain regions and/or time. The majority of these spatio-temporal differences were detected before birth, with subsequent increases in the similarity among regional transcriptomes. The transcriptome is organized into distinct co-expression networks, and shows sex-biased gene expression and exon usage. We also profiled trajectories of genes associated with neurobiological categories and diseases, and identified associations between single nucleotide polymorphisms and gene expression. This study provides a comprehensive data set on the human brain transcriptome and insights into the transcriptional foundations of human neurodevelopment.}, Author = {Kang, Hyo Jung and Kawasawa, Yuka Imamura and Cheng, Feng and Zhu, Ying and Xu, Xuming and Li, Mingfeng and Sousa, Andr{\'e} M M and Pletikos, Mihovil and Meyer, Kyle A and Sedmak, Goran and Guennel, Tobias and Shin, Yurae and Johnson, Matthew B and Krsnik, Zeljka and Mayer, Simone and Fertuzinhos, Sofia and Umlauf, Sheila and Lisgo, Steven N and Vortmeyer, Alexander and Weinberger, Daniel R and Mane, Shrikant and Hyde, Thomas M and Huttner, Anita and Reimers, Mark and Kleinman, Joel E and Sestan, Nenad}, Date-Added = {2011-11-01 18:40:45 -0400}, Date-Modified = {2013-09-25 20:44:04 +0000}, Doi = {10.1038/nature10523}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {cerebral cortex; lateralization; asymmetry; hemisphere; Grants; behavior; Hand Strength; handedness; Laterality; human; gene; forelimb; language; infant; Gene Expression}, Month = {Oct}, Number = {7370}, Pages = {483-9}, pmid = {22031440}, Pst = {epublish}, Title = {Spatio-temporal transcriptome of the human brain}, Volume = {478}, Year = {2011}, url = {papers/Kang_Nature2011.pdf}} @article{Torborg:2005, Abstract = {Blockade of retinal waves prevents the segregation of retinogeniculate afferents into eye-specific layers in the visual thalamus. However, the key features of retinal waves that drive this refinement are controversial. Some manipulations of retinal waves lead to normal eye-specific segregation but others do not. By comparing retinal spiking patterns in several mutant mice with differing levels of eye-specific segregation, we show that the presence of high-frequency bursts synchronized across neighboring retinal ganglion cells correlates with robust eye-specific segregation and that the presence of high levels of asynchronous spikes does not inhibit this segregation. These findings provide a possible resolution to previously described discrepancies regarding the role of retinal waves in retinogeniculate segregation.}, Author = {Torborg, Christine L and Hansen, Kristi A and Feller, Marla B}, Date-Added = {2011-10-21 13:55:32 -0400}, Date-Modified = {2011-10-21 13:57:32 -0400}, Doi = {10.1038/nn1376}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Technique; Spontaneous activity; Retina; Retinal Ganglion Cells; 21 Activity-development; 21 Neurophysiology; multielectrode; array; neuron; development; LGN; topographic map; sensory map; visual system; Structure-Activity Relationship; Mice; Transgenic}, Mesh = {Action Potentials; Animals; Connexins; Electrophysiology; Geniculate Bodies; Mice; Mice, Knockout; Ocular Physiological Phenomena; Reaction Time; Receptors, Nicotinic; Retina; Retinal Ganglion Cells; Synaptic Transmission}, Month = {Jan}, Number = {1}, Pages = {72-8}, Pmc = {PMC1463890}, pmid = {15608630}, Pst = {ppublish}, Title = {High frequency, synchronized bursting drives eye-specific segregation of retinogeniculate projections}, Volume = {8}, Year = {2005}, url = {papers/Torborg_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1376}} @article{Torborg:2004, Abstract = {The projection of retinal ganglion cell axons to the dorsal lateral geniculate nucleus of the thalamus (dLGN) is organized into eye-specific layers, which are macroscopic structures that reflect the bulk organization of thousands of axons. The processes that underlie the formation of these layers is the focus of research in several laboratories. The recent advent of fluorescently tagged tracers allows for the simultaneous visualization of axons from both eyes in the same dLGN section and therefore the analysis of axonal segregation patterns. However, the techniques traditionally used to quantify eye-specific segregation are far from standardized. Here we present an analysis method that objectively quantifies the extent of segregation. We apply this analyses to dLGN images from mice with normal retinogeniculate projection patterns and genetically altered mice with dramatically altered projection patterns. In addition, we compare dLGN images acquired at different optical resolutions to measure the spatial scale over which we can determine segregation unambiguously.}, Author = {Torborg, Christine L and Feller, Marla B}, Date-Added = {2011-10-21 13:54:04 -0400}, Date-Modified = {2011-10-21 13:55:11 -0400}, Doi = {10.1016/j.jneumeth.2003.11.019}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {Technique; histology; Histological Techniques; anterograde tracing; retina; LGN; visual system; development; Retinal Ganglion Cells}, Mesh = {Animals; Animals, Newborn; Axons; Fluorescent Dyes; Functional Laterality; Geniculate Bodies; Hydrazines; Image Processing, Computer-Assisted; Mice; Microscopy, Confocal; Normal Distribution; Organic Chemicals; Retina; Retinal Ganglion Cells; Visual Pathways}, Month = {May}, Number = {1-2}, Pages = {17-26}, pmid = {15020085}, Pst = {ppublish}, Title = {Unbiased analysis of bulk axonal segregation patterns}, Volume = {135}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2003.11.019}} @article{Bossert:2011, Abstract = {In a rat model of context-induced relapse to heroin, we identified sparsely distributed ventral medial prefrontal cortex (mPFC) neurons that were activated by the heroin-associated context. Selective pharmacogenetic inactivation of these neurons inhibited context-induced drug relapse. A small subset of ventral mPFC neurons formed neuronal ensembles that encode the learned associations between heroin reward and heroin-associated contexts; re-activation of these neuronal ensembles by drug-associated contexts during abstinence provoked drug relapse.}, Author = {Bossert, Jennifer M and Stern, Anna L and Theberge, Florence R M and Cifani, Carlo and Koya, Eisuke and Hope, Bruce T and Shaham, Yavin}, Date-Added = {2011-10-13 15:24:17 -0400}, Date-Modified = {2011-10-13 15:28:57 -0400}, Doi = {10.1038/nn.2758}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Immediate-Early Proteins; genes; transgenic; rat; Transgenes; frontiers review}, Mesh = {Analgesics, Opioid; Animals; Disease Models, Animal; Heroin; Heroin Dependence; Nerve Net; Neurons; Prefrontal Cortex; Rats; Recurrence; Substance Withdrawal Syndrome}, Month = {Apr}, Number = {4}, Pages = {420-2}, Pmc = {PMC3077927}, pmid = {21336273}, Pst = {ppublish}, Title = {Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin}, Volume = {14}, Year = {2011}, url = {papers/Bossert_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2758}} @article{Koya:2009, Abstract = {Learned associations between effects of abused drugs and the drug administration environment are important in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although correlations have been observed between nucleus accumbens neuronal activity and responsivity to drugs and drug cues, no technique exists for selectively manipulating these activated neurons and establishing their causal role in behavioral effects of drugs and drug cues. Here we describe a new approach, which we term the 'Daun02 inactivation method', that selectively inactivates a minority of neurons previously activated by cocaine in an environment repeatedly paired with cocaine to demonstrate a causal role for these activated neurons in context-specific cocaine-induced psychomotor sensitization in rats. This method provides a new tool for studying the causal roles of selectively activated neurons in behavioral effects of drugs and drug cues and in other learned behaviors.}, Author = {Koya, Eisuke and Golden, Sam A and Harvey, Brandon K and Guez-Barber, Danielle H and Berkow, Alexander and Simmons, Danielle E and Bossert, Jennifer M and Nair, Sunila G and Uejima, Jamie L and Marin, Marcelo T and Mitchell, Timothy B and Farquhar, David and Ghosh, Sukhen C and Mattson, Brandi J and Hope, Bruce T}, Date-Added = {2011-10-13 15:01:06 -0400}, Date-Modified = {2011-10-13 15:01:49 -0400}, Doi = {10.1038/nn.2364}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Immediate-Early Proteins; gene; transgenic; mice; frontiers review}, Mesh = {Animals; Behavior, Animal; Cocaine; Cocaine-Related Disorders; Cues; Daunorubicin; Disease Models, Animal; Dopamine Uptake Inhibitors; Learning; Male; Neuronal Plasticity; Neurons; Neuropharmacology; Neurotoxins; Nucleus Accumbens; Psychomotor Performance; Rats; Rats, Sprague-Dawley; Rats, Transgenic}, Month = {Aug}, Number = {8}, Pages = {1069-73}, Pmc = {PMC2752202}, pmid = {19620976}, Pst = {ppublish}, Title = {Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization}, Volume = {12}, Year = {2009}, url = {papers/Koya_NatNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2364}} @article{Blank:2011, Abstract = {Down syndrome (DS) is a developmental disorder caused by a third chromosome 21 in humans (Trisomy 21), leading to neurological deficits and cognitive impairment. Studies in mouse models of DS suggest that cognitive deficits in the adult are associated with deficits in synaptic learning and memory mechanisms, but it is unclear whether alterations in the early wiring and refinement of neuronal circuits contribute to these deficits. Here, we show that early developmental refinement of visual circuits is perturbed in mouse models of Down syndrome. Specifically, we find excessive eye-specific segregation of retinal axons in the dorsal lateral geniculate nucleus. Indeed, the degree of refinement scales with defects in the "Down syndrome critical region" (DSCR) in a dose-dependent manner. We further identify Dscam (Down syndrome cell adhesion molecule), a gene within the DSCR, as a regulator of eye-specific segregation of retinogeniculate projections. Although Dscam is not the sole gene in the DSCR contributing to enhanced refinement in trisomy, Dscam dosage clearly regulates cell spacing and dendritic fasciculation in a specific class of retinal ganglion cells. Thus, altered developmental refinement of visual circuits that occurs before sensory experience is likely to contribute to visual impairment in individuals with Down syndrome.}, Author = {Blank, Martina and Fuerst, Peter G and Stevens, Beth and Nouri, Navid and Kirkby, Lowry and Warrier, Deepti and Barres, Ben A and Feller, Marla B and Huberman, Andrew D and Burgess, Robert W and Garner, Craig C}, Date-Added = {2011-10-11 10:37:44 -0400}, Date-Modified = {2011-10-11 10:39:27 -0400}, Doi = {10.1523/JNEUROSCI.6015-10.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; Structure-Activity Relationship; connectivity; neocortex; LGN; retina; visual system; Spontaneous activity; structural remodeling}, Mesh = {Algorithms; Animals; Bicyclo Compounds, Heterocyclic; Cell Adhesion Molecules; Cell Count; Dendrites; Dose-Response Relationship, Drug; Down Syndrome; Fasciculation; Gene Dosage; Geniculate Bodies; Immunohistochemistry; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Microelectrodes; Neurons, Afferent; Nicotinic Agonists; Pyridines; Retina; Retinal Ganglion Cells; Trisomy; Visual Pathways}, Month = {Apr}, Number = {15}, Pages = {5764-76}, pmid = {21490218}, Pst = {ppublish}, Title = {The Down syndrome critical region regulates retinogeniculate refinement}, Volume = {31}, Year = {2011}, url = {papers/Blank_JNeurosci2011.pdf}} @article{Guo:2011, Abstract = {DNA methylation has been traditionally viewed as a highly stable epigenetic mark in postmitotic cells. However, postnatal brains appear to show stimulus-induced methylation changes, at least in a few identified CpG dinucleotides. How extensively the neuronal DNA methylome is regulated by neuronal activity is unknown. Using a next-generation sequencing-based method for genome-wide analysis at single-nucleotide resolution, we quantitatively compared the CpG methylation landscape of adult mouse dentate granule neurons in vivo before and after synchronous neuronal activation. About 1.4% of 219,991 CpGs measured showed rapid active demethylation or de novo methylation. Some modifications remained stable for at least 24 h. These activity-modified CpGs showed a broad genomic distribution with significant enrichment in low-CpG density regions, and were associated with brain-specific genes related to neuronal plasticity. Our study implicates modification of the neuronal DNA methylome as a previously underappreciated mechanism for activity-dependent epigenetic regulation in the adult nervous system.}, Author = {Guo, Junjie U and Ma, Dengke K and Mo, Huan and Ball, Madeleine P and Jang, Mi-Hyeon and Bonaguidi, Michael A and Balazer, Jacob A and Eaves, Hugh L and Xie, Bin and Ford, Eric and Zhang, Kun and Ming, Guo-Li and Gao, Yuan and Song, Hongjun}, Date-Added = {2011-10-07 13:29:41 -0400}, Date-Modified = {2011-10-07 14:09:21 -0400}, Doi = {10.1038/nn.2900}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {memory; Learning; epigenetic; Methylation; neuron; activity manipulation; plasticity; Adult Neurogenesis; mouse; Dentate Gyrus; hippocampus; Genomics}, Number = {10}, Pages = {1345-51}, pmid = {21874013}, Pst = {epublish}, Title = {Neuronal activity modifies the DNA methylation landscape in the adult brain}, Volume = {14}, Year = {2011}, url = {papers/Guo_NatNeurosci2011.pdf}} @article{Feller:1997, Abstract = {In the developing mammalian retina, spontaneous waves of action potentials are present in the ganglion cell layer weeks before vision. These waves are known to be generated by a synaptically connected network of amacrine cells and retinal ganglion cells, and exhibit complex spatiotemporal patterns, characterized by shifting domains of coactivation. Here, we present a novel dynamical model consisting of two coupled populations of cells that quantitatively reproduces the experimentally observed domain sizes, interwave intervals, and wavefront velocity profiles. Model and experiment together show that the highly correlated activity generated by retinal waves can be explained by a combination of random spontaneous activation of cells and the past history of local retinal activity.}, Author = {Feller, M B and Butts, D A and Aaron, H L and Rokhsar, D S and Shatz, C J}, Date-Added = {2011-10-04 12:52:40 -0400}, Date-Modified = {2011-10-04 12:54:09 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal wave paper; Spontaneous activity}, Mesh = {Animals; Ferrets; Models, Neurological; Retina; Retinal Ganglion Cells}, Month = {Aug}, Number = {2}, Pages = {293-306}, pmid = {9292720}, Pst = {ppublish}, Title = {Dynamic processes shape spatiotemporal properties of retinal waves}, Volume = {19}, Year = {1997}, url = {papers/Feller_Neuron1997.pdf}} @article{Douglas:2006, Abstract = {The coherence thresholds to discriminate the direction of motion in random-dot kinematograms were measured in rats and mice. Performance was best in the rats when dot displacement from frame-to-frame was about 2 degrees, and frame duration was less than 100 ms. Mice had coherence thresholds similar to those of rats when tested at the same step size and frame duration. Although the lowest thresholds in the rats and mice occasionally reached human levels, average rodent values ( approximately 25%) were 2-3 times higher than those of humans. These data indicate that the rodent and primate visual systems are similar in that both have local motion detectors and a system for extracting global motion from a noisy signal.}, Author = {Douglas, R M and Neve, A and Quittenbaum, J P and Alam, N M and Prusky, G T}, Date-Added = {2011-09-23 10:06:07 -0400}, Date-Modified = {2011-09-23 10:15:44 -0400}, Doi = {10.1016/j.visres.2006.02.025}, Journal = {Vision Res}, Journal-Full = {Vision research}, Keywords = {mouse; function; Behavior; visual system; Retina; visual cortex; plasticity; acuity; Sensory Deprivation; 21 Activity-development; Binocular; Monocular; bilateral; sensory map; topographic map; rat}, Mesh = {Animals; Discrimination (Psychology); Female; Humans; Mice; Mice, Inbred C57BL; Motion Perception; Pattern Recognition, Visual; Photic Stimulation; Psychophysics; Rats; Rats, Long-Evans; Sensory Thresholds; Species Specificity; Visual Cortex}, Month = {Sep}, Number = {18}, Pages = {2842-7}, pmid = {16647739}, Pst = {ppublish}, Title = {Perception of visual motion coherence by rats and mice}, Volume = {46}, Year = {2006}, url = {papers/Douglas_VisionRes2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.visres.2006.02.025}} @article{Prusky:2006, Abstract = {Plasticity of vision mediated through binocular interactions has been reported in mammals only during a "critical" period in juvenile life, wherein monocular deprivation (MD) causes an enduring loss of visual acuity (amblyopia) selectively through the deprived eye. Here, we report a different form of interocular plasticity of vision in adult mice in which MD leads to an enhancement of the optokinetic response (OKR) selectively through the nondeprived eye. Over 5 d of MD, the spatial frequency sensitivity of the OKR increased gradually, reaching a plateau of approximately 36% above pre-deprivation baseline. Eye opening initiated a gradual decline, but sensitivity was maintained above pre-deprivation baseline for 5-6 d. Enhanced function was restricted to the monocular visual field, notwithstanding the dependence of the plasticity on binocular interactions. Activity in visual cortex ipsilateral to the deprived eye was necessary for the characteristic induction of the enhancement, and activity in visual cortex contralateral to the deprived eye was necessary for its maintenance after MD. The plasticity also displayed distinct learning-like properties: Active testing experience was required to attain maximal enhancement and for enhancement to persist after MD, and the duration of enhanced sensitivity after MD was extended by increasing the length of MD, and by repeating MD. These data show that the adult mouse visual system maintains a form of experience-dependent plasticity in which the visual cortex can modulate the normal function of subcortical visual pathways.}, Author = {Prusky, Glen T and Alam, Nazia M and Douglas, Robert M}, Date-Added = {2011-09-23 10:05:40 -0400}, Date-Modified = {2011-09-23 10:14:14 -0400}, Doi = {10.1523/JNEUROSCI.3396-06.2006}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {mouse; function; Behavior; visual system; Retina; visual cortex; plasticity; acuity; Sensory Deprivation; 21 Activity-development; Binocular; Monocular; bilateral; sensory map; topographic map}, Mesh = {Animals; Contrast Sensitivity; Eye Enucleation; Female; Functional Laterality; Male; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Nystagmus, Optokinetic; Photic Stimulation; Sensory Deprivation; Sensory Thresholds; Space Perception; Time Factors; Vision, Monocular; Visual Acuity; Visual Cortex; Visual Fields; Visual Pathways}, Month = {Nov}, Number = {45}, Pages = {11554-61}, pmid = {17093076}, Pst = {ppublish}, Title = {Enhancement of vision by monocular deprivation in adult mice}, Volume = {26}, Year = {2006}, url = {papers/Prusky_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3396-06.2006}} @article{Prusky:2004, Abstract = {Little is known about the spatial vision of mice or of the role the visual cortex plays in mouse visual perception. In order to provide baseline information upon which to evaluate the spatial vision of experimentally and genetically altered mice, we used the visual water task to assess the contrast sensitivity and grating acuity of normal C57BL/6 mice. We then ablated striate cortex (V1) bilaterally and re-measured the same visual functions. Intact mice displayed an inverse "U"-shaped contrast sensitivity curve with a maximum sensitivity near 0.2 cycles/degree (c/d). Grating acuity, measured either by discriminating a sine-wave grating from an equiluminant gray, or vertical from horizontal sine wave gratings, was near 0.55 c/d. Grating acuity and contrast sensitivity were reduced significantly following aspiration of V1. The mouse visual system exhibits fundamental mammalian characteristics, including the feature that striate cortex is involved in processing visual information with the highest sensitivity and spatial frequency.}, Author = {Prusky, G T and Douglas, R M}, Date-Added = {2011-09-23 10:05:30 -0400}, Date-Modified = {2011-09-23 10:15:31 -0400}, Doi = {10.1016/j.visres.2004.09.001}, Journal = {Vision Res}, Journal-Full = {Vision research}, Keywords = {mouse; function; Behavior; visual system; Retina; visual cortex; plasticity; acuity; Sensory Deprivation; 21 Activity-development; Binocular; Monocular; bilateral; sensory map; topographic map}, Mesh = {Animals; Contrast Sensitivity; Discrimination (Psychology); Disease Models, Animal; Female; Mice; Mice, Inbred C57BL; Models, Animal; Pattern Recognition, Visual; Sensory Thresholds; Visual Acuity; Visual Cortex}, Month = {Dec}, Number = {28}, Pages = {3411-8}, pmid = {15536009}, Pst = {ppublish}, Title = {Characterization of mouse cortical spatial vision}, Volume = {44}, Year = {2004}, url = {papers/Prusky_VisionRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.visres.2004.09.001}} @article{Prusky:2008, Abstract = {Developmentally regulated plasticity of vision has generally been associated with "sensitive" or "critical" periods in juvenile life, wherein visual deprivation leads to loss of visual function. Here we report an enabling form of visual plasticity that commences in infant rats from eye opening, in which daily threshold testing of optokinetic tracking, amid otherwise normal visual experience, stimulates enduring, visual cortex-dependent enhancement (>60%) of the spatial frequency threshold for tracking. The perceptual ability to use spatial frequency in discriminating between moving visual stimuli is also improved by the testing experience. The capacity for inducing enhancement is transitory and effectively limited to infancy; however, enhanced responses are not consolidated and maintained unless in-kind testing experience continues uninterrupted into juvenile life. The data show that selective visual experience from infancy can alone enable visual function. They also indicate that plasticity associated with visual deprivation may not be the only cause of developmental visual dysfunction, because we found that experientially inducing enhancement in late infancy, without subsequent reinforcement of the experience in early juvenile life, can lead to enduring loss of function.}, Author = {Prusky, Glen T and Silver, Byron D and Tschetter, Wayne W and Alam, Nazia M and Douglas, Robert M}, Date-Added = {2011-09-23 10:05:28 -0400}, Date-Modified = {2011-09-23 10:14:10 -0400}, Doi = {10.1523/JNEUROSCI.1940-08.2008}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {mouse; function; Behavior; visual system; Retina; visual cortex; plasticity; acuity; Sensory Deprivation; 21 Activity-development; Binocular; Monocular; bilateral; sensory map; topographic map}, Mesh = {Analysis of Variance; Animals; Animals, Newborn; Eye; Female; GABA Agonists; Male; Motion; Muscimol; Neuronal Plasticity; Nystagmus, Optokinetic; Photic Stimulation; Rats; Rats, Long-Evans; Sensory Thresholds; Vision, Ocular; Visual Cortex; Visual Fields; Visual Perception}, Month = {Sep}, Number = {39}, Pages = {9817-27}, pmid = {18815266}, Pst = {ppublish}, Title = {Experience-dependent plasticity from eye opening enables lasting, visual cortex-dependent enhancement of motion vision}, Volume = {28}, Year = {2008}, url = {papers/Prusky_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1940-08.2008}} @article{Tschetter:2011, Abstract = {Animal model studies of amblyopia have generally concluded that enduring effects of monocular deprivation (MD) on visual behavior (i.e., loss of visual acuity) are limited to the deprived eye, and are restricted to juvenile life. We have previously reported, however, that lasting effects of MD on visual function can be elicited in adulthood by stimulating visuomotor experience through the non-deprived eye. To test whether stimulating experience would also induce interocular plasticity of vision in infancy, we assessed in rats from eye-opening on postnatal day (P) 15, the effect of pairing MD with the daily experience of measuring thresholds for optokinetic tracking (OKT). MD with visuomotor experience from P15 to P25 led to a ~60% enhancement of the spatial frequency threshold for OKT through the non-deprived eye during the deprivation, which was followed by loss-of-function (~60% below normal) through both eyes when the deprived eye was opened. Reduced thresholds were maintained into adulthood with binocular OKT experience from P25 to P30. The ability to generate the plasticity and maintain lost function was dependent on visual cortex. Strictly limiting the period of deprivation to infancy by opening the deprived eye at P19 resulted in a comparable loss-of-function. Animals with reduced OKT responses also had significantly reduced visual acuity, measured independently in a discrimination task. Thus, experience-dependent cortical plasticity that can lead to amblyopia is present earlier in life than previously recognized.}, Author = {Tschetter, Wayne W and Douglas, Robert M and Prusky, Glen T}, Date-Added = {2011-09-23 10:05:23 -0400}, Date-Modified = {2011-09-23 10:14:04 -0400}, Doi = {10.3389/fnsys.2011.00044}, Journal = {Front Syst Neurosci}, Journal-Full = {Frontiers in systems neuroscience}, Keywords = {mouse; function; Behavior; visual system; Retina; visual cortex; plasticity; acuity; Sensory Deprivation; 21 Activity-development; Binocular; Monocular; bilateral; sensory map; topographic map}, Pages = {44}, Pmc = {PMC3118448}, pmid = {21720522}, Pst = {ppublish}, Title = {Experience-induced interocular plasticity of vision in infancy}, Volume = {5}, Year = {2011}, url = {papers/Tschetter_FrontSystNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fnsys.2011.00044}} @article{Huberman:2009, Abstract = {Motion detection is an essential component of visual processing. On-Off direction-selective retinal ganglion cells (On-Off DSGCs) detect objects moving along specific axes of the visual field due to their precise retinal circuitry. The brain circuitry of On-Off DSGCs, however, is largely unknown. We report a mouse with GFP expressed selectively by the On-Off DSGCs that detect posterior motion (On-Off pDSGCs), allowing two-photon targeted recordings of their light responses and delineation of their complete map of central connections. On-Off pDSGCs project exclusively to the dorsal lateral geniculate nucleus and superior colliculus and in both targets form synaptic lamina that are separate from a lamina corresponding to non-DSGCs. Thus, individual On-Off DSGC subtypes are molecularly distinct and establish circuits that map specific qualities of directional motion to dedicated subcortical areas. This suggests that each RGC subtype represents a unique parallel pathway whose synaptic specificity in the retina is recapitulated in central targets.}, Author = {Huberman, Andrew D and Wei, Wei and Elstrott, Justin and Stafford, Ben K and Feller, Marla B and Barres, Ben A}, Date-Added = {2011-09-22 22:34:03 -0400}, Date-Modified = {2011-09-22 22:35:38 -0400}, Doi = {10.1016/j.neuron.2009.04.014}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {retina; Retinal Ganglion Cells; Superior Colliculus; Afferent Pathways; connectivity; sensory map; topographic map; Mouse; 21 Activity-development; Structure-Activity Relationship; structural remodeling}, Mesh = {Animals; Brain Mapping; Geniculate Bodies; Green Fluorescent Proteins; Luminescent Agents; Mice; Mice, Inbred C57BL; Mice, Transgenic; Motion Perception; Retinal Ganglion Cells; Superior Colliculi; Synapses; Visual Pathways}, Month = {May}, Number = {3}, Pages = {327-34}, Pmc = {PMC3140054}, pmid = {19447089}, Pst = {ppublish}, Title = {Genetic identification of an On-Off direction-selective retinal ganglion cell subtype reveals a layer-specific subcortical map of posterior motion}, Volume = {62}, Year = {2009}, url = {papers/Huberman_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.04.014}} @article{Huberman:2007, Abstract = {Eye-specific visual connections are a prominent model system for exploring how precise circuits develop in the CNS and, in particular, for addressing the role of neural activity in synapse elimination and axon refinement. Recent experiments have identified the features of spontaneous retinal activity that mediate eye-specific retinogeniculate segregation, the synaptic events associated with this process, and the importance of axon guidance cues for organizing the overall layout of eye-specific maps. The classic model of ocular dominance column development, in which spontaneous retinal activity plays a crucial role, has also gained new support. Although many outstanding questions remain, the mechanisms that instruct eye-specific circuit development are becoming clear.}, Author = {Huberman, Andrew D}, Date-Added = {2011-09-22 22:31:42 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Doi = {10.1016/j.conb.2007.01.005}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {mouse; visual system; visual cortex; retina; topographic map; sensory map; review; currOpinRvw}, Mesh = {Animals; Cell Communication; Cell Differentiation; Geniculate Bodies; Growth Cones; Humans; Nerve Growth Factors; Retina; Synaptic Transmission; Visual Cortex; Visual Pathways}, Month = {Feb}, Number = {1}, Pages = {73-80}, pmid = {17254766}, Pst = {ppublish}, Title = {Mechanisms of eye-specific visual circuit development}, Volume = {17}, Year = {2007}, url = {papers/Huberman_CurrOpinNeurobiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2007.01.005}} @article{Huberman:2011, Abstract = {Understanding the neural basis of visual perception is a long-standing fundamental goal of neuroscience. Historically, most vision studies were carried out on humans, macaques and cats. Over the past 5 years, however, a growing number of researchers have begun using mice to parse the mechanisms underlying visual processing; the rationale is that, despite having relatively poor acuity, mice are unmatched in terms of the variety and sophistication of tools available to label, monitor and manipulate specific cell types and circuits. In this review, we discuss recent advances in understanding the mouse visual system at the anatomical, receptive field and perceptual level, focusing on the opportunities and constraints those features provide toward the goal of understanding how vision works.}, Author = {Huberman, Andrew D and Niell, Cristopher M}, Date-Added = {2011-09-22 22:25:11 -0400}, Date-Modified = {2013-01-29 17:47:16 +0000}, Doi = {10.1016/j.tins.2011.07.002}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {toread; mouse; visual system; visual cortex; retina; topographic map; sensory map; review}, Month = {Sep}, Number = {9}, Pages = {464-73}, pmid = {21840069}, Pst = {ppublish}, Title = {What can mice tell us about how vision works?}, Volume = {34}, Year = {2011}, url = {papers/Huberman_TrendsNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2011.07.002}} @article{Reillo:2011, Abstract = {The cerebral cortex of large mammals undergoes massive surface area expansion and folding during development. Specific mechanisms to orchestrate the growth of the cortex in surface area rather than in thickness are likely to exist, but they have not been identified. Analyzing multiple species, we have identified a specialized type of progenitor cell that is exclusive to mammals with a folded cerebral cortex, which we named intermediate radial glia cell (IRGC). IRGCs express Pax6 but not Tbr2, have a radial fiber contacting the pial surface but not the ventricular surface, and are found in both the inner subventricular zone and outer subventricular zone (OSVZ). We find that IRGCs are massively generated in the OSVZ, thus augmenting the numbers of radial fibers. Fanning out of this expanding radial fiber scaffold promotes the tangential dispersion of radially migrating neurons, allowing for the growth in surface area of the cortical sheet. Accordingly, the tangential expansion of particular cortical regions was preceded by high proliferation in the underlying OSVZ, whereas the experimental reduction of IRGCs impaired the tangential dispersion of neurons and resulted in a smaller cortical surface. Thus, the generation of IRGCs plays a key role in the tangential expansion of the mammalian cerebral cortex.}, Author = {Reillo, Isabel and de Juan Romero, Camino and Garc{\'\i}a-Cabezas, Miguel {\'A}ngel and Borrell, V{\'\i}ctor}, Date-Added = {2011-09-22 14:47:20 -0400}, Date-Modified = {2011-09-22 14:49:44 -0400}, Doi = {10.1093/cercor/bhq238}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {grants; ideas; retina; Spontaneous activity; Afferent Pathways; Neocortex; visual cortex; radial glia; neurogenesis; retinal wave paper; ontogenetic column; Thalamus; LGN; 21 Activity-development; Structure-Activity Relationship; plasticity}, Month = {Jul}, Number = {7}, Pages = {1674-94}, pmid = {21127018}, Pst = {ppublish}, Title = {A role for intermediate radial glia in the tangential expansion of the mammalian cerebral cortex}, Volume = {21}, Year = {2011}, url = {papers/Reillo_CerebCortex2011.pdf}} @article{Olavarria:1984, Abstract = {Following multiple injections of horseradish peroxidase into the posterior neocortex of one hemisphere, we examined the distribution of retrogradely labeled cells and anterogradely labeled terminations in tangential and coronal sections through contralateral areas 17 and 18 in three groups of adult mice: normal-eyed (ZRDCT-n and C57Bl/6J strains), congenitally anophthalmic (ZRDCT-an strain), neonatally enucleated (ZRDCT-n strain). In agreement with previous studies, we observed that the pattern of callosal connections in areas 17 and 18 of normal-eyed mice contains the following features: (1) a dense band of callosal cells and terminations separating the interiors of areas 17 and 18, which have relatively few callosal connections, (2) a ring-like configuration anterolateral to area 17, (3) a region of dense labeling lateral to area 18, (4) a narrow band of labeling bridging the posterior portion of area 18, and (5) a region of labeling anteromedial to area 17. We find that all these features of the normal callosal pattern are recognizable in congenitally anophthalmic mice. Their presence in mice that never had eyes supports the hypothesis that central visual pathways can develop many aspects of their connectivity in the absence of input from the periphery. However, we also find that the details of certain features of the callosal pattern in congenitally eyeless mice often differ from those of the same features in normal-eyed mice, and that the between-animal variability in the appearance of these features is higher in eyeless mice. These latter findings indicate that the eyes are needed during normal development to fine-tune the pattern of callosal connections. Our results also reveal that the callosal pattern in neonatally enucleated mice does not differ significantly from that in congenitally anophthalmic mice, indicating that the period in which the eyes guide callosal development extends into postnatal life. While the present data do not delineate the time course of this period, the finding of similarly abnormal callosal patterns in congenitally anophthalmic and neonatally enucleated mice suggests that the eyes exert little if any influence prenatally. Finally, examination of coronal sections indicates that the laminar distribution of callosal connections develops normally in both groups of eyeless mice.}, Author = {Olavarria, J and van Sluyters, R C}, Date-Added = {2011-09-22 13:57:29 -0400}, Date-Modified = {2011-09-22 14:15:35 -0400}, Doi = {10.1002/cne.902300209}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {bilateral; callosal; visual cortex; Occipital Lobe; mouse; mutant; Albinism; connectivity; Sensory Deprivation; sensory map; topographic map; tracer; retrograde tracing; retina}, Mesh = {Animals; Animals, Newborn; Anophthalmos; Cats; Corpus Callosum; Cricetinae; Eye; Mice; Rats; Retina; Species Specificity; Visual Pathways}, Month = {Dec}, Number = {2}, Pages = {249-68}, pmid = {6512020}, Pst = {ppublish}, Title = {Callosal connections of the posterior neocortex in normal-eyed, congenitally anophthalmic, and neonatally enucleated mice}, Volume = {230}, Year = {1984}, url = {papers/Olavarria_JCompNeurol1984.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902300209}} @article{Rakic:1991, Abstract = {The cerebral cortex is divisible into a number of cytoarchitectonic areas, but developmental mechanisms that regulate their number and size remain unknown. Here we provide evidence that reducing the population of selected thalamic fibers projecting into the primary visual cortex (area 17) of monkeys during midgestation induces the formation of a novel cytoarchitectonic area situated along the border of and embedded within area 17. This region, termed area X, differs cytoarchitectonically from both area 17 and the adjacent secondary visual cortex (area 18). We propose that an aberrant combination of thalamic and cortical connections acting on a portion of prospective area 17 deprived of its normal thalamic input may result in formation of a hybrid cortex. Our results support the protomap hypothesis of cortical parcellation and suggest how during evolution new cytoarchitectonic regions may arise by cell-cell interactions that depend on a unique combination of intrinsic properties of cortical neurons and afferent fibers.}, Author = {Rakic, P and Su{\~n}er, I and Williams, R W}, Date-Added = {2011-09-22 13:00:04 -0400}, Date-Modified = {2011-09-22 13:01:47 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Sensory Deprivation; monkey; Macaca fascicularis; Neocortex; visual cortex; Occipital Lobe; Afferent Pathways; 21 Activity-development; Structure-Activity Relationship; structural remodeling; plasticity; self organization; retina; topographic map; sensory map; bilateral; visual system}, Mesh = {Animals; Computer Graphics; Fetus; Macaca mulatta; Neurons; Reference Values; Retina; Visual Cortex}, Month = {Mar}, Number = {6}, Pages = {2083-7}, Pmc = {PMC51173}, pmid = {2006147}, Pst = {ppublish}, Title = {A novel cytoarchitectonic area induced experimentally within the primate visual cortex}, Volume = {88}, Year = {1991}, url = {papers/Rakic_ProcNatlAcadSciUSA1991.pdf}} @article{Kuljis:1990, Abstract = {The visual cortex in primates consists of an array of anatomically and chemically identifiable cellular modules (hypercolumns) with distinct physiological properties. For example, layers II/III in the macaque monkey contain a regular array of cytochrome oxidase-rich blobs. Furthermore, the surrounding cytochrome oxidase-poor interblob regions have a higher density of neuropeptide Y-positive aspiny stellate cells. Neurons in the blobs are thought to mediate predominantly low spatial frequencies and color vision, while those in the interblobs appear to be engaged in pattern vision and high spatial frequency analysis. In this study we examined the role of the retina in the development of hypercolumns. A bilateral retinal ablation was performed in embryos at midgestation, before any photoreceptors had established contacts with other retinal neurons and before layers II/III of the cortex--or their synaptic connection--had been generated. We found that the cortex in operated animals had cytochrome oxidase blobs and that their size and spacing were normal. In addition, neuropeptide Y-containing neurons were preferentially distributed in the interblob region as in control animals. Our findings indicate that some basic aspects of the cyto- and chemoarchitectonic organization of the cerebral cortex, which presumably evolved for the analysis of form and color, can emerge in the absence of cues from the retinal photoreceptors that mediate these attributes of vision.}, Author = {Kuljis, R O and Rakic, P}, Date-Added = {2011-09-22 12:47:54 -0400}, Date-Modified = {2011-09-22 12:49:26 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Sensory Deprivation; retina; monkey; Macaca fascicularis; visual cortex; Neocortex; 21 Activity-development; Structure-Activity Relationship; structural remodeling; self organization; Afferent Pathways}, Mesh = {Aging; Animals; Animals, Newborn; Electron Transport Complex IV; Macaca mulatta; Neurons; Neuropeptide Y; Photoreceptor Cells; Retina; Visual Cortex}, Month = {Jul}, Number = {14}, Pages = {5303-6}, Pmc = {PMC54311}, pmid = {2164675}, Pst = {ppublish}, Title = {Hypercolumns in primate visual cortex can develop in the absence of cues from photoreceptors}, Volume = {87}, Year = {1990}, url = {papers/Kuljis_ProcNatlAcadSciUSA1990.pdf}} @article{Dehay:1991, Abstract = {Bilateral enucleation in the macaque fetus causes an areal reduction of an otherwise normal striate cortex. Here we show that in early operated animals this reduction is accompanied by a separation of striate and prostriate cortices which are normally contiguous. However this induced separation does not correspond to the areal reduction of striate cortex, indicating that extrinsic signals regulate either the proliferation and/or survival of striate cortical neurons.}, Author = {Dehay, C and Horsburgh, G and Berland, M and Killackey, H and Kennedy, H}, Date-Added = {2011-09-22 12:38:26 -0400}, Date-Modified = {2011-09-22 12:39:43 -0400}, Journal = {Brain Res Dev Brain Res}, Journal-Full = {Brain research. Developmental brain research}, Keywords = {Binocular; Monocular; 21 Activity-development; Structure-Activity Relationship; structural remodeling; Apoptosis; Neocortex; visual cortex; Occipital Lobe; bilateral; sensory map; topographic map; monkey; Sensory Deprivation; Macaca fascicularis}, Mesh = {Animals; Embryonic and Fetal Development; Eye Enucleation; Macaca fascicularis; Visual Cortex}, Month = {Sep}, Number = {1}, Pages = {137-41}, pmid = {1760867}, Pst = {ppublish}, Title = {The effects of bilateral enucleation in the primate fetus on the parcellation of visual cortex}, Volume = {62}, Year = {1991}, url = {papers/Dehay_BrainResDevBrainRes1991.pdf}} @article{Chalupa:1984, Abstract = {During fetal development of the cat's visual system there is a marked overproliferation of optic nerve axons. In utero binocular interaction contributes to the severity of fiber loss since removal of an eye during gestation attenuates axon loss in the remaining optic nerve. The purpose of the present study was to determine whether this reduced loss of optic nerve fibers is due to a failure of retraction by supernumerary axon branches or to a reduction in ganglion cell death. To resolve this issue, we compared the number of ganglion cells and optic nerve fibers in adult cats which had one eye removed at known gestational ages. Retinal ganglion cells were backfilled with horseradish peroxidase and counts were made from retinal wholemounts. The axon complement was assessed with an electron microscopic assay. In the retinas of a normal cat we estimated 151,000 and 152,000 ganglion cells. The optic nerves of two other normal cats contained approximately 158,000 and 159,000 axons. In comparison, an animal enucleated on embryonic day 42 had 180,000 ganglion cells and 178,000 optic nerve fibers, while in an animal enucleated on embryonic day 51 the corresponding estimates were 182,000 and 190,000. The close agreement between cell and fiber counts indicates that axonal bifurcation does not contribute appreciably to the axon surplus in the optic nerve of prenatally enucleated cats. These results demonstrate that prenatal binocular interaction regulates the size of the mature retinal ganglion cell population.}, Author = {Chalupa, L M and Williams, R W and Henderson, Z}, Date-Added = {2011-09-22 12:35:57 -0400}, Date-Modified = {2011-09-22 12:37:16 -0400}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {Competitive Behavior; self organization; Retinal Ganglion Cells; interaction; Binocular; Monocular; 21 Activity-development; Structure-Activity Relationship; Apoptosis; Afferent Pathways; visual system; cat; retina; Embryo and Fetal Development}, Mesh = {Animals; Cats; Cell Count; Cell Survival; Geniculate Bodies; Gestational Age; Optic Nerve; Retina; Retinal Ganglion Cells; Superior Colliculi}, Month = {Aug}, Number = {4}, Pages = {1039-46}, pmid = {6483189}, Pst = {ppublish}, Title = {Binocular interaction in the fetal cat regulates the size of the ganglion cell population}, Volume = {12}, Year = {1984}, url = {papers/Chalupa_Neuroscience1984.pdf}} @article{Rakic:1981a, Author = {Rakic, P}, Date-Added = {2011-09-22 12:23:14 -0400}, Date-Modified = {2011-09-22 12:29:06 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; Binocular; Monocular; Structure-Activity Relationship; structural remodeling; plasticity; visual system; Visual Cortex; monkey; Macaca fascicularis}, Mesh = {Animals; Axons; Brain; Female; Functional Laterality; Geniculate Bodies; Macaca mulatta; Microscopy, Electron; Pregnancy; Retina; Synapses; Visual Cortex; Visual Perception}, Month = {Nov}, Number = {4523}, Pages = {928-31}, pmid = {7302569}, Pst = {ppublish}, Title = {Development of visual centers in the primate brain depends on binocular competition before birth}, Volume = {214}, Year = {1981}, url = {papers/Rakic_Science1981.pdf}} @article{Rakic:1977a, Author = {Rakic, P}, Date-Added = {2011-09-22 12:19:50 -0400}, Date-Modified = {2011-09-22 12:21:16 -0400}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {visual system; visual cortex; retina; 21 Activity-development; Afferent Pathways; neurogenesis;}, Mesh = {Animals; Animals, Newborn; Autoradiography; Cell Differentiation; Cell Division; Cell Movement; Fucose; Geniculate Bodies; Gestational Age; Haplorhini; Macaca; Macaca mulatta; Proline; Retina; Superior Colliculi; Thymidine; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Apr}, Number = {961}, Pages = {245-60}, pmid = {19781}, Pst = {ppublish}, Title = {Prenatal development of the visual system in rhesus monkey}, Volume = {278}, Year = {1977}, url = {papers/Rakic_PhilosTransRSocLondBBiolSci1977.pdf}} @article{Rakic:1977, Author = {Rakic, P}, Date-Added = {2011-09-22 12:19:49 -0400}, Date-Modified = {2011-09-22 12:20:32 -0400}, Doi = {10.1002/cne.901760103}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {LGN; monkey; Macaca fascicularis; visual system; neurogenesis; migration; neuron}, Mesh = {Animals; Autoradiography; Cell Movement; Geniculate Bodies; Haplorhini; Humans; Macaca mulatta; Mitosis; Retina; Species Specificity}, Month = {Nov}, Number = {1}, Pages = {23-52}, pmid = {409739}, Pst = {ppublish}, Title = {Genesis of the dorsal lateral geniculate nucleus in the rhesus monkey: site and time of origin, kinetics of proliferation, routes of migration and pattern of distribution of neurons}, Volume = {176}, Year = {1977}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901760103}} @article{Land:1979, Abstract = {In the normal newborn rat the retinotectal pathway from each eye distributes across the whole area of both the ipsilateral and contralateral superior colliculus. Most of the ipsilateral projection retracts during the first ten postnatal days to produce the normal adult pattern, but retraction fails to occur if one eye is removed at birth.}, Author = {Land, P W and Lund, R D}, Date-Added = {2011-09-22 11:47:36 -0400}, Date-Modified = {2011-09-22 11:51:03 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {optic tectum; Superior Colliculus; retina; visual system; Monocular; Binocular; 21 Activity-development; Structure-Activity Relationship; structural remodeling; connectivity}, Mesh = {Albinism; Animals; Animals, Newborn; Functional Laterality; Optic Chiasm; Rats; Retina; Superior Colliculi; Visual Pathways}, Month = {Aug}, Number = {4407}, Pages = {698-700}, pmid = {462177}, Pst = {ppublish}, Title = {Development of the rat's uncrossed retinotectal pathway and its relation to plasticity studies}, Volume = {205}, Year = {1979}, url = {papers/Land_Science1979.pdf}} @article{Rakic:1974a, Abstract = {Autoradiographic evidence after injection of tritiated thymidine indicates that cell position in the laminae of the monkey visual cortex is systematically related to time of cell orgin. The earliest-formed neurons, destined for the deepest stratum, arise at about embryonic day 45, and the last ones, destined for the outermost cell stratum, form at about day 102; cells of intervening layers are generated at intervening times. No neocortical neurons are produced in the last two prenatal months or after birth. Compared to cortical neurons in rodents, those in the monkey arise earlier, and the "inside-out" relation of cell position to time of origin is more rigid.}, Author = {Rakic, P}, Date-Added = {2011-09-22 11:03:15 -0400}, Date-Modified = {2011-09-22 11:04:01 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {monkey; Macaca fascicularis; Neocortex; Cerebral Cortex; neurogenesis; development}, Mesh = {Animals; Autoradiography; Brain Mapping; Cell Differentiation; Cell Movement; Female; Gestational Age; Haplorhini; Macaca; Neurons; Pregnancy; Thymidine; Tritium; Visual Cortex}, Month = {Feb}, Number = {123}, Pages = {425-7}, pmid = {4203022}, Pst = {ppublish}, Title = {Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition}, Volume = {183}, Year = {1974}, url = {papers/Rakic_Science1974a.pdf}} @article{Tolonen:2007, Abstract = {Recent experimental studies have shown that developing cortex in several animals species, including humans, exhibits spontaneous intermittent activity that is believed to be crucial for the proper wiring of early brain networks. The present study examined the developmental changes in these spontaneous activity transients (SAT) and in other ongoing cortical activities in human preterm babies. Full-band electroencephalography (FbEEG) recordings were obtained from 16 babies at conceptional ages between 32.8 and 40 wk. We examined the SATs and the intervening ongoing cortical activities (inter-SAT; iSAT) with average waveforms, their variance and power, as well as with wavelet-based time-frequency analyses. Our results show, that the low frequency power and the variance of the average waveform of SAT decrease during development. There was a simultaneous increase in the activity at higher frequencies, with most pronounced increase at theta-alpha range (4-9 Hz). In addition to the overall increase, the activity at higher frequencies showed an increased grouping into bursts that are nested in the low frequency (0.5-1 Hz) waves. Analysis of the iSAT epochs showed a developmental increase in power at lower frequencies in quiet sleep. There was an increase in a wide range of higher frequencies (4-16 Hz), whereas the ratio of beta (16-30 Hz) and theta-alpha (4-9 Hz) range activity declined, indicating a preferential increase at theta-alpha range activity. Notably, SAT and iSAT activities remained distinct throughout the development in all measures used in our study. The present results are consistent with the idea that SAT and the other ongoing cortical activities are distinct functional entities. Recognition of these two basic mechanisms in the cortical activity in preterm human babies opens new rational approaches for an evaluation and monitoring of early human brain function.}, Author = {Tolonen, M and Palva, J M and Andersson, S and Vanhatalo, S}, Date-Added = {2011-09-22 09:30:02 -0400}, Date-Modified = {2013-08-19 20:53:13 +0000}, Doi = {10.1016/j.neuroscience.2006.12.070}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {retinal wave paper; visual system; human; Fetus; EEG; Electroencephalography; Spontaneous activity; 21 Activity-development; sensory map; Occipital Lobe; visual cortex; currOpinRvw}, Mesh = {Beta Rhythm; Cerebral Cortex; Cortical Synchronization; Electroencephalography; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Theta Rhythm}, Month = {Mar}, Number = {3}, Pages = {997-1006}, pmid = {17307296}, Pst = {ppublish}, Title = {Development of the spontaneous activity transients and ongoing cortical activity in human preterm babies}, Volume = {145}, Year = {2007}, url = {papers/Tolonen_Neuroscience2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2006.12.070}} @article{Vanhatalo:2005, Abstract = {Spontaneous transients of correlated activity are a characteristic feature of immature brain structures, where they are thought to be crucial for the establishment of precise neuronal connectivity. Studies on experimental animals have shown that this kind of early activity in cortical structures is composed of long-lasting, intermittent network events, which undergo a developmental decline that is closely paralleled by the maturation of GABAergic inhibition. In order to examine whether similar events occur in the immature human cortex, we performed direct current-coupled electroencephalography (EEG) recordings from sleeping preterm babies. We show now that much of the preterm EEG activity is confined to spontaneous, slow activity transients. These transients are characterized by a large voltage deflection that nests prominent oscillatory activity in several frequency bands covering the whole frequency spectrum of the preterm EEG (<0.1-30 Hz). The slow voltage deflections had an amplitude of up to 800 microV. Most of these 'giant' events originated in the temporo-occipital areas, with a maximum rate of about 8/min, and their occurrence as well as amplitude showed a decline by the time of normal birth. In age-matched fetal brain tissue, this decrease in the spontaneous activity transients was associated with a developmental up-regulation of the neuronal chloride extruder K+-Cl- cotransporter 2, a crucial molecule for the generation of inhibitory GABAergic Cl- currents. Our work indicates that slow endogenous activity transients in the immature human neocortex are mostly confined to the prenatal stage and appear to be terminated in parallel with the maturation of functional GABAergic inhibition.}, Author = {Vanhatalo, Sampsa and Palva, J Matias and Andersson, Sture and Rivera, Claudio and Voipio, Juha and Kaila, Kai}, Date-Added = {2011-09-22 09:19:31 -0400}, Date-Modified = {2013-08-19 20:53:24 +0000}, Doi = {10.1111/j.1460-9568.2005.04459.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {retinal wave paper; human; EEG; Electroencephalography; Occipital Lobe; visual cortex; visual system; Spontaneous activity; oscillations; synchrony; 21 Activity-development; 21 Neurophysiology; currOpinRvw}, Mesh = {Cerebral Cortex; Cloning, Molecular; Electroencephalography; Electrophysiology; Humans; In Situ Hybridization; Infant; Infant, Newborn; Neocortex; Symporters; Up-Regulation; gamma-Aminobutyric Acid}, Month = {Dec}, Number = {11}, Pages = {2799-804}, pmid = {16324114}, Pst = {ppublish}, Title = {Slow endogenous activity transients and developmental expression of K+-Cl- cotransporter 2 in the immature human cortex}, Volume = {22}, Year = {2005}, url = {papers/Vanhatalo_EurJNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2005.04459.x}} @article{Wong:1999, Abstract = {Many pathways in the developing visual system are restructured and become highly organized even before vision occurs. Yet the developmental processes underlying the remodeling of visual connectivity are crucially dependent on retinal activity. Surprisingly, the immature and light-insensitive retina spontaneously generates a pattern of rhythmic bursting activity during the period when the connectivity patterns of retinal ganglion cells are shaped. Spatially, the activity is seen to spread across the retina in the form of waves that bring into synchrony the bursts of neighboring cells. Waves are present in the developing retina of higher and lower vertebrates, which suggests that this form of activity may be a common and fundamental mechanism employed in the activity-dependent refinement of early patterns of visual connections. Unraveling the cues encoded by the waves promises to provide important insights into how interactions driven by specific patterns of activity could lead to the modification of connectivity during development.}, Author = {Wong, R O}, Date-Added = {2011-09-22 09:10:36 -0400}, Date-Modified = {2013-05-31 16:17:18 +0000}, Doi = {10.1146/annurev.neuro.22.1.29}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {retinal wave paper; retina; visual system; Spontaneous activity; 21 Activity-development; Structure-Activity Relationship; structural remodeling; sensory map; topographic map; development; review; currOpinRvw}, Mesh = {Animals; Electrophysiology; Embryo, Mammalian; Embryo, Nonmammalian; Embryonic and Fetal Development; Retina; Visual Pathways}, Pages = {29-47}, pmid = {10202531}, Pst = {ppublish}, Title = {Retinal waves and visual system development}, Volume = {22}, Year = {1999}, url = {papers/Wong_AnnuRevNeurosci1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.22.1.29}} @article{Uchiyama:1989, Abstract = {Two types of centrifugal pathways to the retina have been found in the vertebrates, according to the location of the cell bodies and presence or absence of connections with the optic tectum. One type is represented by the isthmo-optic nucleus (ION) of birds and, therefore, termed "ION-type" retinopetal system. The other type is termed "non-ION-type" retinopetal system. The ION-type retinopetal systems have been found in the cyclostomes, teleosts, reptiles, and birds. This review describes the anatomy and physiology of the ION-type retinopetal systems, mainly of birds and teleosts. On the basis of anatomical and physiological evidence cited in this review, the ION-type retinopetal systems can be regarded as the tectofugal pathways to the retina. The function of the ION-type retinopetal systems is discussed in detail, with special emphasis on their relation to the role of the tectum in mediating visuomotor behavior.}, Author = {Uchiyama, H}, Date-Added = {2011-09-21 13:03:20 -0400}, Date-Modified = {2011-09-21 13:04:38 -0400}, Journal = {Vis Neurosci}, Journal-Full = {Visual neuroscience}, Keywords = {retina;retinopetal;axons;connectivity;Circuit structure-function;histamine;Serotonin;retinal wave paper;Hypothalamus;dorsal raphe;Sleep;centrifugal;Efferent Pathways}, Mesh = {Animals; Retina; Superior Colliculi; Visual Pathways}, Month = {Sep}, Number = {3}, Pages = {183-206}, pmid = {2487102}, Pst = {ppublish}, Title = {Centrifugal pathways to the retina: influence of the optic tectum}, Volume = {3}, Year = {1989}} @article{Gastinger:2005, Abstract = {PURPOSE: To describe serotonergic retinopetal axons in monkeys. METHODS: Whole macaque and baboon retinas, fixed in 4% paraformaldehyde, were labeled with antisera raised against serotonin (5-HT). RESULTS: Several large-diameter 5-HT-immunoreactive (IR) axons emerged from the optic disk. Most axons ran to the peripheral retina, where they branched extensively. Most terminated in the ganglion cell layer, but a few 5-HT-IR axons terminated in distal inner plexiform or within inner nuclear layer. Some axons branched extensively near the fovea, and a dense plexus of 5-HT-IR axons was also found around the optic disk. Varicose 5-HT-IR axons were also associated with blood vessels, especially in the central retina. CONCLUSIONS: Immunoreactive serotonin is present in a distinct population of retinopetal axons in the monkey retina. Receptors for serotonin are present in the primate retinas, and based on physiological studies in other mammals, these retinopetal axons are expected to modulate neuronal activity and regulate blood flow.}, Author = {Gastinger, Matthew J and Bordt, Andrea S and Bernal, Maria P and Marshak, David W}, Date-Added = {2011-09-21 12:52:26 -0400}, Date-Modified = {2011-09-21 12:53:00 -0400}, Doi = {10.1080/02713680500371532}, Journal = {Curr Eye Res}, Journal-Full = {Current eye research}, Keywords = {retina;retinopetal;axons;connectivity;Circuit structure-function;histamine;Serotonin;retinal wave paper;Hypothalamus;dorsal raphe;Sleep;centrifugal;Efferent Pathways}, Mesh = {Animals; Axons; Female; Macaca mulatta; Nerve Fibers; Optic Disk; Papio anubis; Receptors, Serotonin; Retina; Retinal Ganglion Cells; Retinal Vessels; Serotonin; Visual Pathways}, Month = {Dec}, Number = {12}, Pages = {1089-95}, pmid = {16354622}, Pst = {ppublish}, Title = {Serotonergic retinopetal axons in the monkey retina}, Volume = {30}, Year = {2005}, url = {papers/Gastinger_CurrEyeRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/02713680500371532}} @article{Gastinger:1999, Abstract = {PURPOSE: The goal of these experiments was to identify the neurotransmitter in centrifugal axons of the macaque retina. METHODS: Macaca mulatta retinas and optic nerves were fixed overnight in carbodiimide and labeled with an antiserum to histamine with the use of an immunofluorescence technique. RESULTS: Several large histamine-immunoreactive axons ran from the optic nerve head to the peripheral retina, where they branched extensively and terminated in the inner plexiform layer, occasionally alongside retinal blood vessels. Other axons that emerged from the optic nerve head ran in the optic fiber layer to the central retina, circled the fovea, and then returned to the optic disc. These may be the source of histamine-immunoreactive axons that have been observed in central visual areas. No labeled cell bodies were present in the retina. Because perikarya in the posterior hypothalamus are the only known source of histamine in the primate central nervous system and because neurons there can be retrogradely labeled from the cut optic nerve, the histamine-immunoreactive axons must have originated there. CONCLUSIONS: Centrifugal axons in the macaque retina are part of the system of axons containing histamine that originate in the hypothalamus and project throughout the brain. Because the activity of these neurons is highest during the morning, histamine might play a role in preparing the retina to operate in daylight. The contacts of histamine-immunoreactive axons with blood vessels suggest that histamine may also play a role in regulating the retinal microvasculature.}, Author = {Gastinger, M J and O'Brien, J J and Larsen, N B and Marshak, D W}, Date-Added = {2011-09-21 12:36:30 -0400}, Date-Modified = {2011-09-21 12:40:37 -0400}, Journal = {Invest Ophthalmol Vis Sci}, Journal-Full = {Investigative ophthalmology \& visual science}, Keywords = {retina;retinopetal;axons;connectivity;Circuit structure-function;histamine;Serotonin;retinal wave paper;Hypothalamus;dorsal raphe;Sleep;centrifugal;Efferent Pathways}, Mesh = {Animals; Axons; Fluorescent Antibody Technique, Indirect; Histamine; Macaca mulatta; Optic Nerve; Retina; Visual Pathways}, Month = {Feb}, Number = {2}, Pages = {487-95}, pmid = {9950609}, Pst = {ppublish}, Title = {Histamine immunoreactive axons in the macaque retina}, Volume = {40}, Year = {1999}, url = {papers/Gastinger_InvestOphthalmolVisSci1999.pdf}} @article{Takahashi:2005, Abstract = {Previous electrophysiological studies have shown that the commissural connections between the two superior colliculi are mainly inhibitory with fewer excitatory connections. However, the functional roles of the commissural connections are not well understood, so we sought to clarify the physiology of tectal commissural excitation and inhibition of tectoreticular neurons (TRNs) in the "fixation " and "saccade " zones of the superior colliculus (SC). By recording intracellular potentials, we identified TRNs by their antidromic responses to stimulation of the omnipause neuron (OPN) and inhibitory burst neuron (IBN) regions and analyzed the effects of stimulation of the contralateral SC on these TRNs in anesthetized cats. TRNs in the caudal SC (saccade neurons) projected to the IBN region, and received mono- or disynaptic inhibition from the entire rostrocaudal extent of the contralateral SC. In contrast, TRNs in the rostral SC projected to the OPN or IBN region and received monosynaptic excitation from the most rostral level of the contralateral SC, and mono- or disynaptic inhibition from its entire rostrocaudal extent. Among the rostral TRNs with commissural excitation, IBN-projecting TRNs also projected to Forel's field H (vertical gaze center), suggesting that they were most likely saccade neurons related to vertical saccades. In contrast, TRNs projecting only to the OPN region were most likely fixation neurons. Most putative inhibitory neurons in the rostral SC had multiple axon branches throughout the rostrocaudal extent of the contralateral SC, whereas excitatory commissural neurons, most of which were rostral TRNs, distributed terminals to a discrete region in the rostral SC.}, Author = {Takahashi, M and Sugiuchi, Y and Izawa, Y and Shinoda, Y}, Date-Added = {2011-09-20 16:59:04 -0400}, Date-Modified = {2011-09-20 16:59:04 -0400}, Doi = {10.1152/jn.00347.2005}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Mesh = {Action Potentials; Animals; Brain Mapping; Cats; Dose-Response Relationship, Radiation; Electric Stimulation; Evoked Potentials; Excitatory Postsynaptic Potentials; Functional Laterality; Neural Inhibition; Neural Pathways; Neurons; Superior Colliculi; Synapses}, Month = {Sep}, Number = {3}, Pages = {1707-26}, pmid = {16105954}, Pst = {ppublish}, Title = {Commissural excitation and inhibition by the superior colliculus in tectoreticular neurons projecting to omnipause neuron and inhibitory burst neuron regions}, Volume = {94}, Year = {2005}, url = {papers/Takahashi_JNeurophysiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00347.2005}} @article{Lewis:1995, Abstract = {In the rat, callosal cells occupy lateral as well as medial portions of striate cortex. In the region of the border between areas 17 and 18, which contains a representation of the vertical meridian of the visual field, cells projecting through the corpus callosum are concentrated throughout the depth of the cortex. In contrast, in medial portion of striate cortex, where peripheral portions of the visual field are represented, callosal cells are preferentially found in infragranular layers. These differences in topography and laminar distribution suggest that these callosal regions, referred to as medial and lateral callosal regions in the present study, subserve different functions. We explored this possibility by analyzing the patterns of callosal linkages in these two callosal regions. We charted the location of retrogradely labeled cells within striate cortex of one hemisphere after placing restricted injections of one or more fluorescent tracers into selected sites in the contralateral striate cortex. We found the medial and lateral callosal regions have distinctly different topographic organizations. Injections into medial striate cortex of one hemisphere produced labeled cells predominantly in mirror-symmetric loci in medial portions of contralateral striate cortex. The arrangement of these connections suggests that they mediate direct interactions between cortical regions representing visual fields located symmetrically on opposite sides of the vertical meridian of the visual field. In contrast, the mapping in the lateral callosal region is reversed: injections into the 17/18a border produced labeled fields located medial to the contralateral 17/18a border, while injections slightly medial to the 17/18a border produced labeled fields located at the contralateral 17/18a border.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Lewis, J W and Olavarria, J F}, Date-Added = {2011-09-20 14:43:38 -0400}, Date-Modified = {2011-09-20 14:53:31 -0400}, Doi = {10.1002/cne.903610110}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Activity-development; visual cortex; visual system; retina; sensory map; topographic map; synapse formation; Structure-Activity Relationship; structural remodeling; bilateral; mirror symmetry; connectivity;}, Mesh = {Animals; Corpus Callosum; Fluorescent Dyes; Functional Laterality; Neural Pathways; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Skin Pigmentation; Visual Cortex}, Month = {Oct}, Number = {1}, Pages = {119-37}, pmid = {8550874}, Pst = {ppublish}, Title = {Two rules for callosal connectivity in striate cortex of the rat}, Volume = {361}, Year = {1995}, url = {papers/Lewis_JCompNeurol1995.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903610110}} @article{Olavarria:1995a, Abstract = {The effect of neonatal bilateral enucleation on the overall distribution of callosal connections in striate and extrastriate visual cortex of the cat was studied using tangential sections from the physically unfolded and flattened cortex. Callosal neurons were labeled by administering the anatomical tracer horseradish peroxidase directly to the transected corpus callosum. The pattern of callosal connections in binocularly enucleated cats showed both consistent differences and consistent similarities with the pattern in normal cats. In agreement with previous studies, it was found that callosal labeling at the 17/18 border of enucleated cats was considerably sparser than in normal cats. Moreover, we found that the strip containing the majority of labeled cells at the 17/18 border was narrower than in normal cats. In both normal and enucleated cats, scattered cells were distributed on either side of the 17/18 callosal strip, well into areas 17 and 18. In much of extrastriate cortex, the pattern of callosal connectivity in enucleated cats looked surprisingly normal. Details of the callosal pattern that were consistently found in normal cats could also be recognized in binocularly enucleated cats, such as two to four bridges of labeling spanning areas 18 and 19. Also, four zones that were free of callosal connectivity in area 7, on the banks of the suprasylvian sulcus, and in the posterior suprasylvian sulcus were found in both normal and enucleated cats. Finally, as in normal cats, dense cell labeling occurred on the crown of the suprasylvian gyrus at its posterior end, from which it extended laterally across both banks of the suprasylvian sulcus and into the fundus of this sulcus. The results of this study suggest that, although the stabilization of callosal connections at the 17/18 border region appears to depend on visual input, this input plays a less prominent role in the stabilization of callosal connections in extrastriate visual cortex.}, Author = {Olavarria, J F and Van Sluyters, R C}, Date-Added = {2011-09-20 14:40:08 -0400}, Date-Modified = {2011-09-20 14:53:09 -0400}, Doi = {10.1002/cne.903630202}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Activity-development; visual cortex; visual system; retina; sensory map; topographic map; synapse formation; Structure-Activity Relationship; structural remodeling; bilateral; mirror symmetry; connectivity;}, Mesh = {Animals; Cats; Corpus Callosum; Eye Enucleation; Functional Laterality; Reference Values; Visual Cortex; Visual Pathways}, Month = {Dec}, Number = {2}, Pages = {161-76}, pmid = {8642068}, Pst = {ppublish}, Title = {Overall pattern of callosal connections in visual cortex of normal and enucleated cats}, Volume = {363}, Year = {1995}, url = {papers/Olavarria_JCompNeurol1995a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903630202}} @article{Olavarria:1995, Abstract = {Lewis and Olavarria ([1995] J. Comp. Neurol. 361:119-137) showed that the mediolateral organization of callosal linkages differs markedly between medial and lateral regions of striate cortex in the rat. Thus, callosal fibers originating from medial regions of striate cortex interconnect loci that are mirror-symmetric with respect to the midsagittal plane. In contrast, fibers from lateral regions of striate cortex show a reversed pattern of connections: tracer injections into the 17/18a border produce retrograde cell labeling in regions medial to the contralateral 17/18a border, whereas injections placed somewhat medial to the 17/18a border label cells located at the contralateral 17/18a border. Based on the interpretation that callosal fibers from lateral striate cortex connect retinotopically corresponding loci (Lewis and Olavarria [1995] J. Comp. Neurol. 361:119-137) we propose here that the development of the reversed pattern of connections in lateral portions of striate cortex is guided by activity-dependent cues originating from spontaneously active ganglion cells in temporal retina. In the present study we have attempted to falsify this hypothesis by investigating the effects of neonatal bilateral enucleation on the organization of callosal linkages in striate cortex of the rat. Once enucleated rats reached adulthood, we studied the mediolateral organization of callosal connections by placing small injections of different fluorescent tracers into different loci within medial and lateral striate cortex. The analysis of the distribution of retrogradely labeled callosal cells indicated that connections from lateral portions of striate cortex were no longer organized in a reversed fashion, rather, they resembled the mirror image pattern normally found in the medial callosal region, i.e., injections at the 17/18a border produced labeled cells at the opposite 17/18a border, whereas injections into slightly more medial regions produced labeled cells in the opposite, mirror-symmetric location. In addition, we found that enucleation does not alter the organization of callosal linkages in medial portions of striate cortex. Thus, by showing that enucleation significantly changes the pattern of connections from lateral portions of striate cortex, the present study does not falsify, but rather strengthens the hypothesis that interhemispheric correlated activity driven from the temporal retinal crescent guides the normal development of reversed callosal linkages in lateral portions of rat striate cortex. Furthermore, the present study shows that, in the absence of the eyes, the pattern of callosal linkages in lateral portions of striate cortex resembles the mirror image pattern normally found only in medial striate cortex.}, Author = {Olavarria, J F and Li, C P}, Date-Added = {2011-09-20 14:39:58 -0400}, Date-Modified = {2011-09-20 14:53:16 -0400}, Doi = {10.1002/cne.903610111}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Activity-development; visual cortex; visual system; retina; sensory map; topographic map; synapse formation; Structure-Activity Relationship; structural remodeling; bilateral; mirror symmetry; connectivity;}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Corpus Callosum; Eye Enucleation; Functional Laterality; Nerve Fibers; Rats; Visual Cortex; Visual Pathways}, Month = {Oct}, Number = {1}, Pages = {138-51}, pmid = {8550875}, Pst = {ppublish}, Title = {Effects of neonatal enucleation on the organization of callosal linkages in striate cortex of the rat}, Volume = {361}, Year = {1995}, url = {papers/Olavarria_JCompNeurol1995.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903610111}} @article{Olavarria:1985, Abstract = {The distribution of callosal cells and terminals was studied in the posterior neocortex of pups whose ages ranged from 3 to 16 days and in adult rats 2 months of age or older. Callosal cells and terminations were revealed using retrograde (horseradish peroxidase) and anterograde (horseradish peroxidase; tritiated proline) tracing techniques, respectively, and the distribution of callosal connections was analyzed in tangential or coronal histological sections. In agreement with previous studies, we observed that the pattern of callosal connections in areas 17 and 18 of adult rats contains the following features: (1) a dense band of callosal cells and terminations separating the interiors of areas 17 and 18a, (2) a ringlike configuration anterolateral to area 17, (3) a region of dense labeling lateral to area 18a, (4) several narrow bands of labeling that bridge area 18a at different anteroposterior levels, and (5) one or more labeled regions in area 18b. In all these callosal regions, labeled cells and terminations are densely aggregated in layers II-III, Va, and Vc-VIa, and less densely in layer IV and the remaining portions of layers V and VI. High densities of isotope-labeled fibers are also observed in the lower half of layer I. Throughout the interiors of areas 17 and 18a, a significant number of labeled cells are observed in layers Vc-VIa. In contrast to adult rats, in neonates no distinct tangential pattern of callosal connections is apparent. Instead, labeled cells are densely aggregated in two continuous horizontal bands located in cortical layers Va and Vc-VIa, and callosal axons are largely restricted to white matter. During the first 2 postnatal weeks there is a progressive loss of callosal cells in regions that normally have few callosal cells in the adult (e.g., interiors of areas 17 and 18a) and an increase in the number of cells in layers II-IV in regions that are densely callosal in the adult (e.g., callosal regions at the 17/18a border, lateral border of area 18a, and in area 18b). The decrease in the number of callosal cells in the interiors of areas 17 and 18a is more severe in the upper than in the lower band of the immature labeling pattern, and our data from tangential sections indicate that this loss of callosal neurons occurs synchronously across the interiors of these areas. During this period there is also a localized invasion of labeled callosal axons into those regions of gray matter where they will be found in adult life.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Olavarria, J and Van Sluyters, R C}, Date-Added = {2011-09-20 14:38:30 -0400}, Date-Modified = {2011-09-20 14:53:25 -0400}, Doi = {10.1002/cne.902390102}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Activity-development; visual cortex; visual system; retina; sensory map; topographic map; synapse formation; Structure-Activity Relationship; structural remodeling; bilateral; mirror symmetry; connectivity;}, Mesh = {Animals; Autoradiography; Corpus Callosum; Rats; Thalamic Nuclei; Visual Cortex; Visual Pathways}, Month = {Sep}, Number = {1}, Pages = {1-26}, pmid = {4044927}, Pst = {ppublish}, Title = {Organization and postnatal development of callosal connections in the visual cortex of the rat}, Volume = {239}, Year = {1985}, url = {papers/Olavarria_JCompNeurol1985.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902390102}} @article{Leamey:2007, Abstract = {Binocular vision requires an exquisite matching of projections from each eye to form a cohesive representation of the visual world. Eye-specific inputs are anatomically segregated, but in register in the visual thalamus, and overlap within the binocular region of primary visual cortex. Here, we show that the transmembrane protein Ten_m3 regulates the alignment of ipsilateral and contralateral projections. It is expressed in a gradient in the developing visual pathway, which is consistently highest in regions that represent dorsal visual field. Mice that lack Ten_m3 show profound abnormalities in mapping of ipsilateral, but not contralateral, projections, and exhibit pronounced deficits when performing visually mediated behavioural tasks. It is likely that the functional deficits arise from the interocular mismatch, because they are reversed by acute monocular inactivation. We conclude that Ten_m3 plays a key regulatory role in the development of aligned binocular maps, which are required for normal vision.}, Author = {Leamey, Catherine A and Merlin, Sam and Lattouf, Paul and Sawatari, Atomu and Zhou, Xiaohong and Demel, Natasha and Glendining, Kelly A and Oohashi, Toshitaka and Sur, Mriganka and F{\"a}ssler, Reinhard}, Date-Added = {2011-09-19 17:12:40 -0400}, Date-Modified = {2011-09-19 17:12:53 -0400}, Doi = {10.1371/journal.pbio.0050241}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {bilateral; Binocular; Monocular; sensory map; topographic map; visual system; visual cortex; Mouse; mice; 21 Activity-development; Behavior}, Mesh = {Animals; Membrane Proteins; Mice; Mice, Knockout; Nerve Tissue Proteins; Vision, Binocular; Visual Cortex; Visual Fields; Visual Pathways}, Month = {Sep}, Number = {9}, Pages = {e241}, Pmc = {PMC1964777}, pmid = {17803360}, Pst = {ppublish}, Title = {Ten_m3 regulates eye-specific patterning in the mammalian visual pathway and is required for binocular vision}, Volume = {5}, Year = {2007}, url = {papers/Leamey_PLoSBiol2007.pdf}} @article{Leamey:2008, Abstract = {Adult neocortical areas are characterized by marked differences in cytoarchitecture and connectivity that underlie their functional roles. The molecular determinants of these differences are largely unknown. We performed a microarray analysis to identify molecules that define the somatosensory and visual areas during the time when afferent and efferent projections are forming. We identified 122 molecules that are differentially expressed between the regions and confirmed by quantitative polymerase chain reaction 95\% of the 20 genes tested. Two genes were chosen for further investigation: Bcl6 and Ten_m3. Bcl6 was highly expressed in the superficial cortical plate corresponding to developing layer IV of somatosensory cortex at postnatal day (P) 0. This had diminished by P3, but strong expression was found in layer V pyramidal cells by P7 and was maintained until adulthood. Retrograde tracing showed that Bcl6 is expressed in corticospinal neurons. Ten_m3 was expressed in a graded pattern within layer V of caudal cortex that corresponds well with visual cortex. Retrograde tracing and immunostaining showed that Ten_m3 is highly expressed along axonal tracts of projection neurons of the developing visual pathway. Overexpression demonstrated that Ten_m3 promotes homophilic adhesion and neurite outgrowth in vivo. This suggests an important role for Ten_m3 in the development of the visual pathway.}, Author = {Leamey, Catherine A and Glendining, Kelly A and Kreiman, Gabriel and Kang, Ning-Dong and Wang, Kuan H and Fassler, Reinhard and Sawatari, Atomu and Tonegawa, Susumu and Sur, Mriganka}, Date-Added = {2011-09-19 17:11:11 -0400}, Date-Modified = {2011-09-19 17:12:03 -0400}, Doi = {10.1093/cercor/bhm031}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {bilateral; Binocular; Monocular; sensory map; topographic map; visual system; visual cortex; Mouse; mice; 21 Activity-development; Behavior}, Mesh = {Animals; Body Patterning; DNA-Binding Proteins; Gene Expression Regulation, Developmental; Membrane Proteins; Mice; Neocortex; Nerve Tissue Proteins; Somatosensory Cortex; Tissue Distribution; Visual Pathways}, Month = {Jan}, Number = {1}, Pages = {53-66}, pmid = {17478416}, Pst = {ppublish}, Title = {Differential gene expression between sensory neocortical areas: potential roles for Ten_m3 and Bcl6 in patterning visual and somatosensory pathways}, Volume = {18}, Year = {2008}, url = {papers/Leamey_CerebCortex2008.pdf}} @article{Catmur:2009, Abstract = {A core requirement for imitation is a capacity to solve the correspondence problem; to map observed onto executed actions, even when observation and execution yield sensory inputs in different modalities and coordinate frames. Until recently, it was assumed that the human capacity to solve the correspondence problem is innate. However, it is now becoming apparent that, as predicted by the associative sequence learning model, experience, and especially sensorimotor experience, plays a critical role in the development of imitation. We review evidence from studies of non-human animals, children and adults, focusing on research in cognitive neuroscience that uses training and naturally occurring variations in expertise to examine the role of experience in the formation of the mirror system. The relevance of this research depends on the widely held assumption that the mirror system plays a causal role in generating imitative behaviour. We also report original data supporting this assumption. These data show that theta-burst transcranial magnetic stimulation of the inferior frontal gyrus, a classical mirror system area, disrupts automatic imitation of finger movements. We discuss the implications of the evidence reviewed for the evolution, development and intentional control of imitation.}, Author = {Catmur, Caroline and Walsh, Vincent and Heyes, Cecilia}, Date-Added = {2011-09-16 10:22:15 -0400}, Date-Modified = {2011-09-16 10:22:37 -0400}, Doi = {10.1098/rstb.2009.0048}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {Learning; Memory; multisensory integration; function; Behavior; human; Infant; Newborn; neonatal; visual system; 21 Activity-development; mirror neuron}, Mesh = {Animals; Association Learning; Brain; Humans; Imitative Behavior; Magnetic Resonance Imaging; Motor Activity; Transcranial Magnetic Stimulation}, Month = {Aug}, Number = {1528}, Pages = {2369-80}, Pmc = {PMC2865072}, pmid = {19620108}, Pst = {ppublish}, Title = {Associative sequence learning: the role of experience in the development of imitation and the mirror system}, Volume = {364}, Year = {2009}, url = {papers/Catmur_PhilosTransRSocLondBBiolSci2009.pdf}} @article{Cumming:1999, Abstract = {Most neurophysiological accounts of disparity selectivity in neurons of the primary visual cortex (V1) imply that they are selective for absolute retinal disparities. By contrast, a number of psychophysical observations indicate that relative disparities play a more important role in depth perception. During recordings from disparity selective neurons in area V1 of awake behaving monkeys, we used a disparity feedback loop () to add controlled amounts of absolute disparity to a display containing both absolute and relative disparities. This manipulation changed the absolute disparity of all the visible features in the display but left unchanged the relative disparities signalled by these features. The addition of absolute disparities produced clear changes in the neural responses to unchanged external stimuli, which were well predicted by the measured change in absolute disparity: in 45/53 cases, the neuron maintained a consistent firing pattern with respect to absolute disparity so that the manipulation created no significant change in the absolute disparity preferred by the neuron. No neuron in V1 maintained a consistent relationship with relative disparity. We conclude that the relative disparity signals used in primate depth perception are constructed outside area V1.}, Author = {Cumming, B G and Parker, A J}, Date-Added = {2011-09-16 10:18:00 -0400}, Date-Modified = {2011-09-16 10:19:41 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Retina; visual cortex; visual system; sensory map; topographic map; mirror symmetry; bilateral; Binocular; binocular disparity; Monocular; stereotopy; monkey; Macaca; 21 Neurophysiology; extracellular; awake}, Mesh = {Action Potentials; Animals; Depth Perception; Eye Movements; Feedback; Female; Macaca mulatta; Male; Models, Biological; Neurons; Photic Stimulation; Time Factors; Vision Disparity; Vision, Binocular; Visual Cortex; Wakefulness}, Month = {Jul}, Number = {13}, Pages = {5602-18}, pmid = {10377367}, Pst = {ppublish}, Title = {Binocular neurons in V1 of awake monkeys are selective for absolute, not relative, disparity}, Volume = {19}, Year = {1999}, url = {papers/Cumming_JNeurosci1999.pdf}} @article{Ringach:2007, Abstract = {The basic structure of receptive fields and functional maps in primary visual cortex is established without exposure to normal sensory experience and before the onset of the critical period. How the brain wires these circuits in the early stages of development remains unknown. Possible explanations include activity-dependent mechanisms driven by spontaneous activity in the retina and thalamus, and molecular guidance orchestrating thalamo-cortical connections on a fine spatial scale. Here I propose an alternative hypothesis: the blueprint for receptive fields, feature maps, and their inter-relationships may reside in the layout of the retinal ganglion cell mosaics along with a simple statistical connectivity scheme dictating the wiring between thalamus and cortex. The model is shown to account for a number of experimental findings, including the relationship between retinotopy, orientation maps, spatial frequency maps and cytochrome oxidase patches. The theory's simplicity, explanatory and predictive power makes it a serious candidate for the origin of the functional architecture of primary visual cortex.}, Author = {Ringach, Dario L}, Date-Added = {2011-09-16 10:15:42 -0400}, Date-Modified = {2011-09-16 10:17:24 -0400}, Doi = {10.1371/journal.pone.0000251}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {computation biology; Theoretical; Retina; visual cortex; visual system; sensory map; topographic map; mirror symmetry; bilateral; Binocular; binocular disparity; Monocular; stereotopy; Retinal Ganglion Cells; 21 Activity-development; structural remodeling; Structure-Activity Relationship; Spontaneous activity;}, Mesh = {Algorithms; Animals; Brain Mapping; Cats; Computer Simulation; Dominance, Cerebral; Dominance, Ocular; Electron Transport Complex IV; Geniculate Bodies; Models, Neurological; Nerve Tissue Proteins; Retina; Retinal Ganglion Cells; Species Specificity; Thalamus; Vision, Binocular; Visual Cortex; Visual Fields; Visual Pathways}, Number = {2}, Pages = {e251}, Pmc = {PMC1804100}, pmid = {17330140}, Pst = {epublish}, Title = {On the origin of the functional architecture of the cortex}, Volume = {2}, Year = {2007}, url = {papers/Ringach_PLoSOne2007.pdf}} @article{Zihl:1979, Abstract = {Threshold elevation in the periphery of the visual field as a consequence of repetitive stimulation can be abolished by stimulating a mirror-symmetric position in the contralateral visual half-field. A patient suffering from a congenital malformation of the right superior colliculus did not exhibit threshold elevation when stimulated repeatedly in the left visual field. Stimulation in the right visual half-field resulted in the usually observed threshold elevation, but stimulating a mirror-symmetric position in the left visual half-field did not abolish threshold elevation in the right half-field. These observations suggest that: (a) threshold elevation probably occurs as a consequence of collicular adaptation and (b) the mirror-symmetrically organized interhemispheric interaction is mediated at the collicular level.}, Author = {Zihl, J and von Cramon, D}, Date-Added = {2011-09-16 10:15:13 -0400}, Date-Modified = {2011-09-16 10:15:24 -0400}, Journal = {Exp Brain Res}, Journal-Full = {Experimental brain research. Experimentelle Hirnforschung. Exp{\'e}rimentation c{\'e}r{\'e}brale}, Keywords = {Superior Colliculus; optic tectum; Retina; visual cortex; visual system; sensory map; topographic map; mirror symmetry; bilateral; human; Binocular; binocular disparity; Monocular; stereotopy; Adaptation; function; Behavior}, Mesh = {Dominance, Cerebral; Humans; Superior Colliculi; Visual Fields; Visual Pathways; Visual Perception}, Month = {May}, Number = {3}, Pages = {419-24}, pmid = {456450}, Pst = {ppublish}, Title = {Collicular function in human vision}, Volume = {35}, Year = {1979}, url = {papers/Zihl_ExpBrainRes1979.pdf}} @article{Singer:1977, Author = {Singer, W and Zihl, J and P{\"o}ppel, E}, Date-Added = {2011-09-16 10:13:05 -0400}, Date-Modified = {2011-09-16 10:14:31 -0400}, Journal = {Exp Brain Res}, Journal-Full = {Experimental brain research. Experimentelle Hirnforschung. Exp{\'e}rimentation c{\'e}r{\'e}brale}, Keywords = {Superior Colliculus; optic tectum; Retina; visual cortex; visual system; sensory map; topographic map; mirror symmetry; bilateral; human; Binocular; binocular disparity; Monocular; stereotopy; Adaptation; function; Behavior}, Mesh = {Adaptation, Ocular; Attention; Differential Threshold; Functional Laterality; Humans; Retina; Saccades; Visual Cortex; Visual Fields; Visual Pathways; Visual Perception}, Month = {Aug}, Number = {2}, Pages = {173-90}, pmid = {913514}, Pst = {ppublish}, Title = {Subcortical control of visual thresholds in humans: evidence for modality specific and retinotopically organized mechanisms of selective attention}, Volume = {29}, Year = {1977}, url = {papers/Singer_ExpBrainRes1977.pdf}} @article{Boire:2001, Abstract = {The anatomical consequences of unilateral cerebral hemispherectomy in some animal models are reviewed. We have shown that the retinogenigulate pathway undergoes severe degenerative changes in hemispherectomized monkeys, greater than those shown in cats and we proposed that remaining retinal terminals to the dorsal lateral geniculate nucleus have little potential for conveying visual information any further. All subdivisions of the pulvinar undergo severe degeneration following hemispherectomy showing that the ascending tectofugal pathway is also shut off. On the other hand, the retina subserving the blind field is not depleted of ganglion cells which still send normal appearing terminals to the midbrain pretectum and superior colliculus. Visual information from the blind hemifield can thus gain access to the brain and could potentially reach the contralateral cerebral cortex through the midbrain commissure and possibly through thalamic commissural cells.}, Author = {Boire, D and Th{\'e}oret, H and Ptito, M}, Date-Added = {2011-09-16 10:08:18 -0400}, Date-Modified = {2011-09-16 10:11:08 -0400}, Journal = {Prog Brain Res}, Journal-Full = {Progress in brain research}, Keywords = {Superior Colliculus; optic tectum; Retina; visual cortex; visual system; sensory map; topographic map; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral; human; monkey; blindsight; Sensory Deprivation}, Mesh = {Animals; Brain; Models, Neurological; Postoperative Period; Retina; Synaptic Transmission; Visual Cortex; Visual Pathways}, Pages = {379-97}, pmid = {11702556}, Pst = {ppublish}, Title = {Visual pathways following cerebral hemispherectomy}, Volume = {134}, Year = {2001}} @article{Ptito:2001, Abstract = {Destruction of the striate cortex has traditionally been thought to lead to permanent blindness in the contralateral visual field and to the dogma that this region is indispensable for vision in primates. For over 25 years now, evidence has been accumulating that hemianopic human subjects and monkeys possess wide-ranging residual visual capacities or 'blindsight' in the blind part of their visual field. For some researchers, isolated islands of the striate cortex have been associated with patches of degraded vision and made responsible for blindisight. Artefacts such as light scatter, criterion effects, macular sparing, eccentric fixation and minute eye movements have also been linked with the residual vision. For others, the fact that certain aspects of the visual information can be processed without the geniculostriate pathway suggests mediation by the visual subsystems such as extrastriate visual cortical areas which receive visual information via subcortical pathways, that escaped the cortical damage. Subjects who have had a whole cerebral hemisphere removed or disconnected (for the treatment of uncontrollable epilepsy) and who show residual vision in their blind field offer a remarkable opportunity to help clear the controversy regarding the neural substrate of blindsight. Because it is certain that no functional striate or extrastriate cortex remains on the ablated side, these subjects have contributed significantly to identifying the critical pathways involved in blindsight.}, Author = {Ptito, A and Fortin, A and Ptito, M}, Date-Added = {2011-09-16 10:08:15 -0400}, Date-Modified = {2011-09-16 10:10:56 -0400}, Journal = {Prog Brain Res}, Journal-Full = {Progress in brain research}, Keywords = {Superior Colliculus; optic tectum; Retina; visual cortex; visual system; sensory map; topographic map; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral; human; monkey; blindsight; Sensory Deprivation}, Mesh = {Awareness; Brain; Hemianopsia; Humans; Magnetic Resonance Imaging; Postoperative Period; Psychophysics}, Pages = {367-78}, pmid = {11702555}, Pst = {ppublish}, Title = {'Seeing' in the blind hemifield following hemispherectomy}, Volume = {134}, Year = {2001}, url = {papers/Ptito_ProgBrainRes2001.pdf}} @article{Fox:1965, Author = {Fox, M W}, Date = {1965 Apr-Jul}, Date-Added = {2011-09-16 09:50:53 -0400}, Date-Modified = {2011-09-16 09:51:40 -0400}, Journal = {Anim Behav}, Journal-Full = {Animal behaviour}, Keywords = {Retina; visual cortex; visual system; sensory map; topographic map; mirror symmetry; bilateral; Binocular; Monocular; stereotopy; mouse; binocular disparity; function; behavior}, Mesh = {Animals; Depth Perception; Male; Mice; Psychology, Experimental}, Number = {2}, Pages = {232-3}, pmid = {5835839}, Pst = {ppublish}, Title = {The visual cliff test for the study of visual depth perception in the mouse}, Volume = {13}, Year = {1965}, url = {papers/Fox_AnimBehav1965.pdf}} @article{Rodger:2005, Abstract = {Following unilateral optic nerve section in adult PVG hooded rat, the axon guidance cue ephrin-A2 is up-regulated in caudal but not rostral superior colliculus (SC) and the EphA5 receptor is down-regulated in axotomised retinal ganglion cells (RGCs). Changes occur bilaterally despite the retino-collicular projection being mostly crossed. Here we investigate the dynamics of Eph/ephrin expression using in situ hybridization and semi-quantitative immunohistochemistry after localized retinal lesions. Unilateral krypton laser lesions to dorso-nasal retina ablated contralaterally projecting RGCs (DN group); ventro-temporal lesions ablated contralaterally and ipsilaterally projecting RGCs (VT group). Lesions of the entire retina served as controls (Total group). Results are compared to normal animals in which tectal ephrin-A2 and retinal EphA5 are expressed, respectively, as shallow ascending rostro-caudal and naso-temporal gradients. In both SCs of DN and Total groups, tectal ephrin-A2 was up-regulated caudally; in the VT group, expression remained normal bilaterally. Unilateral collicular ablation indicated that bilateral changes in ephrin-A2 expression are mediated via intercollicular pathways. EphA5 expression in the VT group was elevated in the intact nasal region of experimental retinae. For each experimental group, EphA5 expression was also elevated in nasal retina of the opposite eye, resulting in uniform expression across the naso-temporal axis. Up-regulation of ephrin-A2 in caudal, but not rostral, SC suggests the enhancement of developmental positional information as a result of injury. Bilateral increases in retinal EphA5 expression demonstrate that signals for up-regulation operate interocularly. The study demonstrates that signals regulating guidance cue expression are both localized and relayed transneuronally.}, Author = {Rodger, J and Symonds, A C E and Springbett, J and Shen, W-Y and Bartlett, C A and Rakoczy, P E and Beazley, L D and Dunlop, S A}, Date-Added = {2011-09-16 09:43:59 -0400}, Date-Modified = {2011-09-16 09:45:41 -0400}, Doi = {10.1111/j.1460-9568.2005.04381.x}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {Retina; Superior Colliculus; optic tectum; visual system; sensory map; topographic map; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral; Binocular; Monocular; stereotopy; rat; rodent; connectivity; retinopetal; retino-retinal; retino-retino; Eph Family; EphA5; Ephrin-A2; homotypic interaction}, Mesh = {Animals; Cell Count; Cholera Toxin; Denervation; Ephrins; Female; Functional Laterality; Immunohistochemistry; In Situ Hybridization; Models, Neurological; Rats; Receptors, Eph Family; Retina; Superior Colliculi; Up-Regulation}, Month = {Oct}, Number = {8}, Pages = {1840-52}, pmid = {16262624}, Pst = {ppublish}, Title = {Eph/ephrin expression in the adult rat visual system following localized retinal lesions: localized and transneuronal up-regulation in the retina and superior colliculus}, Volume = {22}, Year = {2005}, url = {papers/Rodger_EurJNeurosci2005.pdf}} @article{Chino:1997, Abstract = {In macaque monkeys, the age at which neurons in the primary visual cortex (V1) become sensitive to interocular image disparities, a prerequisite for stereopsis, is a matter of conjecture. To resolve this fundamental issue in binocular vision development, we measured the responsiveness of individual V1 neurons in anesthetized and paralyzed infant monkeys as a function of the relative, interocular, spatial phase of dichoptic sine-wave gratings. We found that an adult-like proportion of units were sensitive to interocular image disparity as early as the sixth postnatal day, several weeks before the onset age for stereopsis in monkeys. The ocular dominance distributions of cells in infant monkeys were also indistinguishable from those of adults. Thus, at or only a few days after birth, V1 neurons are capable of combining neural signals from the two eyes as in adults and are sensitive to interocular image disparities. However, the monocular spatial-frequency response properties of these disparity-sensitive units were immature, and their overall responsiveness was far lower than that in adults. During the first 4 postnatal weeks, both the spatial frequency response properties and the peak response amplitude rapidly improved, which resulted in a corresponding increase in the absolute sensitivity of individual units to interocular disparity. The results demonstrate that early binocular vision development in monkeys is not constrained by a paucity of disparity-sensitive V1 neurons but, instead, by the relative immaturity of the spatial response properties and the overall unresponsiveness of existing disparity-sensitive neurons.}, Author = {Chino, Y M and Smith, 3rd, E L and Hatta, S and Cheng, H}, Date-Added = {2011-09-16 09:12:05 -0400}, Date-Modified = {2011-09-16 09:13:17 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; Retina; visual cortex; visual system; sensory map; topographic map; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral; Binocular; Monocular; stereotopy; monkey; Macaca; binocular disparity}, Mesh = {Animals; Animals, Newborn; Depth Perception; Functional Laterality; Macaca mulatta; Neurons; Vision, Binocular; Vision, Monocular; Visual Cortex}, Month = {Jan}, Number = {1}, Pages = {296-307}, pmid = {8987756}, Pst = {ppublish}, Title = {Postnatal development of binocular disparity sensitivity in neurons of the primate visual cortex}, Volume = {17}, Year = {1997}, url = {papers/Chino_JNeurosci1997.pdf}} @article{Dias:1991, Abstract = {Binocular visual responses can be recorded in two regions of the superficial layers of the superior colliculus of the opossum. The direct binocular region (DBR) represents the binocular portion of the contralateral hemifield whereas the rostral pole (RP) represents the binocular portion of the ipsilateral hemifield. In the present study single units from both of these regions were tested with binocular and monocular stimulation. Most cells in both regions showed response facilitation when both eyes were simultaneously stimulated and, when tested with different binocular disparities, most cells showed broadly-tuned disparity selectivity. DBR units usually preferred disparities near zero whereas RP units had a wider range of preferred disparities, with a tendency toward positive (crossed) values. This data indicates that the superior colliculus of the opossum could provide a neural substrate for a coarse analysis of depth and also might help control vergence eye movements. The different ranges of disparity selectivity of DBR and RP are consistent with the previously reported monocular receptive-field data and suggest that DBR and RP analyze different depths of the 3-dimensional visual scene.}, Author = {Dias, E C and Rocha-Miranda, C E and Bernardes, R F and Schmidt, S L}, Date-Added = {2011-09-16 09:09:43 -0400}, Date-Modified = {2011-09-16 09:11:17 -0400}, Journal = {Exp Brain Res}, Journal-Full = {Experimental brain research. Experimentelle Hirnforschung. Exp{\'e}rimentation c{\'e}r{\'e}brale}, Keywords = {Superior Colliculus; optic tectum; Retina; visual system; sensory map; topographic map; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral; Binocular; Monocular; stereotopy; Opossums/*growth &development; binocular disparity; 21 Neurophysiology; extracellular}, Mesh = {Animals; Neurons; Opossums; Photic Stimulation; Superior Colliculi; Vision, Binocular; Vision, Monocular; Visual Cortex; Visual Perception}, Number = {3}, Pages = {546-52}, pmid = {1783025}, Pst = {ppublish}, Title = {Disparity selective units in the superior colliculus of the opossum}, Volume = {87}, Year = {1991}, url = {papers/Dias_ExpBrainRes1991.pdf}} @article{Coleman:2009, Abstract = {Ocular dominance (OD) plasticity is a classic paradigm for studying the effect of experience and deprivation on cortical development, and is manifested as shifts in the relative strength of binocular inputs to primary visual cortex (V1). The mouse has become an increasingly popular model for mechanistic studies of OD plasticity and, consequently, it is important that we understand how binocularity is constructed in this species. One puzzling feature of the mouse visual system is the gross disparity between the physiological strength of each eye in V1 and their anatomical representation in the projection from retina to the dorsal lateral geniculate nucleus (dLGN). While the contralateral-to-ipsilateral (C/I) ratio of visually evoked responses in binocular V1 is approximately 2:1, the ipsilateral retinal projection is weakly represented in terms of retinal ganglion cell (RGC) density where the C/I ratio is approximately 9:1. The structural basis for this relative amplification of ipsilateral eye responses between retina and V1 is not known. Here we employed neuroanatomical tracing and morphometric techniques to quantify the relative magnitude of each eye's input to and output from the binocular segment of dLGN. Our data are consistent with the previous suggestion that a point in space viewed by both eyes will activate 9 times as many RGCs in the contralateral retina as in the ipsilateral retina. Nonetheless, the volume of the dLGN binocular segment occupied by contralateral retinogeniculate inputs is only 2.4 times larger than the volume occupied by ipsilateral retinogeniculate inputs and recipient relay cells are evenly distributed among the input layers. The results from our morphometric analyses show that this reduction in input volume can be accounted for by a three-to-one convergence of contralateral eye RGC inputs to dLGN neurons. Together, our findings establish that the relative density of feed-forward dLGN inputs determines the C/I response ratio of mouse binocular V1.}, Author = {Coleman, J E and Law, K and Bear, M F}, Date-Added = {2011-09-16 09:04:15 -0400}, Date-Modified = {2011-09-16 09:05:49 -0400}, Doi = {10.1016/j.neuroscience.2009.03.045}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {Retina; visual cortex; visual system; sensory map; topographic map; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral; Binocular; Monocular; stereotopy; mouse; retinotopy; connectivity; Anatomy;}, Mesh = {Animals; Dominance, Ocular; Geniculate Bodies; Mice; Mice, Inbred C57BL; Neurons; Retinal Ganglion Cells; Vision, Binocular; Visual Cortex}, Month = {Jun}, Number = {2}, Pages = {561-71}, Pmc = {PMC2735235}, pmid = {19327388}, Pst = {ppublish}, Title = {Anatomical origins of ocular dominance in mouse primary visual cortex}, Volume = {161}, Year = {2009}, url = {papers/Coleman_Neuroscience2009.pdf}} @article{Berman:1975, Abstract = {1. Binocularly driven neurones with small receptive fields near the area centralis were recorded in the cat's superior colliculus. 2. Binocular interaction was tested by stimulating both eyes simultaneously with a single moving stimulus at various retinal disparities. 3. Collicular cells in general showed strong summation or even facilitation when the images of the stimulus were in exact correspondence on the receptive fields, sometimes with occlusion when they were out of register. The range of retinal disparity over which there was additive interaction could be as little as 1 or 2 deg, almost as narrow as for the most precisely tuned neurones in the visual cortex. Even cells with large receptive fields sometimes showed a narrow range of binocular interaction. 4. Non-directional cells generally exhibited weaker summation and broader disparity selectivity than did direction-selective cells. 5. Some neurones with virtually no response to a stimulus in one of the eyes can exhibit marked binocular interaction. Other apparently monocular cells show little or no binocular interaction. 6. The disparity of the centres of the receptive fields was measured after correcting for small eye movements, which were assessed by two different techniques. For 132 cells the measured distribution of horizontal disparity (range 4.5 deg; S.D. 0.93 deg) was significantly broader than that of vertical disparity (range 2.2 deg; S.D. 0.52 deg). Sources of error in these measurements are considered. 7. The results are discussed in relation to the known connexions between visual cortex and superior colliculus and the possible role of the latter in the regulation of eye movements.}, Author = {Berman, N and Blakemore, C and Cynader, M}, Date-Added = {2011-09-16 09:02:31 -0400}, Date-Modified = {2011-09-16 09:03:48 -0400}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {Superior Colliculus; optic tectum; 21 Neurophysiology; Retina; visual cortex; visual system; sensory map; topographic map; remodeling; mirror symmetry; bilateral; Binocular; Monocular; stereotopy; cat}, Mesh = {Action Potentials; Animals; Cats; Eye Movements; Lasers; Microelectrodes; Neurons; Photic Stimulation; Photoreceptor Cells; Superior Colliculi; Vision, Ocular}, Month = {Apr}, Number = {3}, Pages = {595-615}, Pmc = {PMC1309437}, pmid = {1133788}, Pst = {ppublish}, Title = {Binocular interaction in the cat's superior colliculus}, Volume = {246}, Year = {1975}, url = {papers/Berman_JPhysiol1975.pdf}} @article{Sylvester:2007, Abstract = {Eye patching has revealed enhanced saccadic latencies or attention effects when orienting toward visual stimuli presented in the temporal versus nasal hemifields of humans. Such behavioral advantages have been tentatively proposed to reflect possible temporal-nasal differences in the retinotectal pathway to the superior colliculus, rather than in the retinogeniculate pathway or visual cortex. However, this has not been directly tested with physiological measures in humans. Here, we examined responses of the human superior colliculus (SC) to contralateral visual field stimulation, using high spatial resolution fMRI, while manipulating which hemifield was stimulated and orthogonally which eye was patched. The SC responded more strongly to visual stimulation when eye-patching made this stimulation temporal rather than nasal. In contrast, the lateral geniculate nucleus (LGN) plus retinotopic cortical areas V1-V3 did not show any temporal-nasal differences and differed from the SC in this respect. These results provide the first direct physiological demonstration in humans that SC shows temporal-nasal differences that LGN and early visual cortex apparently do not. This may represent a temporal hemifield bias in the strength of the retinotectal pathway, leading to a preference for the contralateral hemifield in the contralateral eye.}, Author = {Sylvester, Richard and Josephs, Oliver and Driver, Jon and Rees, Geraint}, Date-Added = {2011-09-16 09:00:11 -0400}, Date-Modified = {2011-09-16 09:01:51 -0400}, Doi = {10.1152/jn.00835.2006}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Retina; Superior Colliculus; visual system; sensory map; topographic map; stereotopy; human; fmri; retinotopy; function}, Mesh = {Adult; Brain Stem; Functional Laterality; Geniculate Bodies; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Occipital Lobe; Oxygen; Photic Stimulation; Superior Colliculi; Temporal Lobe; Vision, Monocular; Visual Cortex; Visual Fields; Visual Pathways}, Month = {Feb}, Number = {2}, Pages = {1495-502}, pmid = {17135475}, Pst = {ppublish}, Title = {Visual FMRI responses in human superior colliculus show a temporal-nasal asymmetry that is absent in lateral geniculate and visual cortex}, Volume = {97}, Year = {2007}, url = {papers/Sylvester_JNeurophysiol2007.pdf}} @article{Held:1980, Abstract = {Stereograms were presented in a two-choice preference procedure. The mean age at which stereopsis was first demonstrable was 16 weeks. By a mean age of 21 weeks, infants had achieved stereoacuity of 1 minute of arc or better. In comparison with the relatively slow development of visual acuity, the time course for the development of stereoacuity is extremely rapid.}, Author = {Held, R and Birch, E and Gwiazda, J}, Date-Added = {2011-09-16 08:55:37 -0400}, Date-Modified = {2011-09-16 08:57:07 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {retinal wave paper; Retina; visual cortex; visual system; sensory map; topographic map; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral; Binocular; Monocular; stereotopy; human}, Mesh = {Age Factors; Depth Perception; Humans; Infant; Visual Acuity}, Month = {Sep}, Number = {9}, Pages = {5572-4}, Pmc = {PMC350104}, pmid = {6933571}, Pst = {ppublish}, Title = {Stereoacuity of human infants}, Volume = {77}, Year = {1980}, url = {papers/Held_ProcNatlAcadSciUSA1980.pdf}} @article{Wang:2010b, Abstract = {Changes of ocular dominance in the visual cortex can be induced by visual manipulations during a critical period in early life. However, the role of critical period plasticity in normal development is unknown. Here we show that at the onset of this time window, the preferred orientations of individual cortical cells in the mouse are mismatched through the two eyes and the mismatch decreases and reaches adult levels by the end of the period. Deprivation of visual experience during this period irreversibly blocks the binocular matching of orientation preference, but has no effect in adulthood. The critical period of binocular matching can be delayed by long-term visual deprivation from birth, like that of ocular dominance plasticity. These results demonstrate that activity-dependent changes induced by normal visual experience during the well-studied critical period serve to match eye-specific inputs in the cortex, thus revealing a physiological role for critical period plasticity during normal development.}, Author = {Wang, Bor-Shuen and Sarnaik, Rashmi and Cang, Jianhua}, Date-Added = {2011-09-15 11:44:41 -0400}, Date-Modified = {2013-08-28 15:21:35 +0000}, Doi = {10.1016/j.neuron.2010.01.002}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology;Spontaneous activity;retina;visual cortex;visual system;function;in vivo;Binocular; ocular dominance; plasticity; Monocular; Sensory Deprivation; topographic map; sensory map; bilateral; currOpinRvw}, Mesh = {Age Factors; Animals; Animals, Newborn; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Orientation; Photic Stimulation; Sensory Deprivation; Vision, Binocular; Visual Cortex}, Month = {Jan}, Number = {2}, Pages = {246-56}, Pmc = {PMC2822731}, pmid = {20152130}, Pst = {ppublish}, Title = {Critical period plasticity matches binocular orientation preference in the visual cortex}, Volume = {65}, Year = {2010}, url = {papers/Wang_Neuron2010.pdf}} @article{Bunt:1981, Abstract = {Intraocular HRP injections in E16-21 embryos show that during the normal development of the central optic projections in hooded and albino rats many optic axons grow through the chiasm into the contralateral eye. This retino-retinal projection disappears shortly after birth. This suggests that an initial, imprecise guidance of growing axons is followed by a selective elimination of axons taking aberrant pathways and failing to make appropriate synapses.}, Author = {Bunt, S M and Lund, R D}, Date-Added = {2011-09-14 19:16:53 -0400}, Date-Modified = {2011-09-14 19:18:24 -0400}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {retinopetal; 21 Activity-development; structural remodeling; Structure-Activity Relationship; Binocular; bilateral; visual system; Retina; Retinal Ganglion Cells; retino-retino; retino-retinal;}, Mesh = {Animals; Axonal Transport; Axons; Female; Functional Laterality; Horseradish Peroxidase; Optic Nerve; Pregnancy; Rats; Retina; Superior Colliculi; Synapses}, Month = {May}, Number = {2}, Pages = {399-404}, pmid = {6165434}, Pst = {ppublish}, Title = {Development of a transient retino-retinal pathway in hooded and albino rats}, Volume = {211}, Year = {1981}, url = {papers/Bunt_BrainRes1981.pdf}} @article{Ferrari:2006, Abstract = {The emergence of social behaviors early in life is likely crucial for the development of mother-infant relationships. Some of these behaviors, such as the capacity of neonates to imitate adult facial movements, were previously thought to be limited to humans and perhaps the ape lineage. Here we report the behavioral responses of infant rhesus macaques (Macaca mulatta) to the following human facial and hand gestures: lip smacking, tongue protrusion, mouth opening, hand opening, and opening and closing of eyes (control condition). In the third day of life, infant macaques imitate lip smacking and tongue protrusion. On the first day of life, the model's mouth openings elicited a similar matched behavior (lip smacking) in the infants. These imitative responses are present at an early stage of development, but they are apparently confined to a narrow temporal window. Because lip smacking is a core gesture in face-to-face interactions in macaques, neonatal imitation may serve to tune infants' affiliative responses to the social world. Our findings provide a quantitative description of neonatal imitation in a nonhuman primate species and suggest that these imitative capacities, contrary to what was previously thought, are not unique to the ape and human lineage. We suggest that their evolutionary origins may be traced to affiliative gestures with communicative functions.}, Author = {Ferrari, Pier F and Visalberghi, Elisabetta and Paukner, Annika and Fogassi, Leonardo and Ruggiero, Angela and Suomi, Stephen J}, Date-Added = {2011-09-14 18:09:00 -0400}, Date-Modified = {2011-09-14 18:09:00 -0400}, Doi = {10.1371/journal.pbio.0040302}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Mesh = {Animals; Animals, Newborn; Behavior, Animal; Facial Expression; Female; Imitative Behavior; Macaca mulatta; Male; Maternal Behavior; Mouth; Nonverbal Communication; Social Behavior; Time Factors; Tongue}, Month = {Sep}, Number = {9}, Pages = {e302}, Pmc = {PMC1560174}, pmid = {16953662}, Pst = {ppublish}, Title = {Neonatal imitation in rhesus macaques}, Volume = {4}, Year = {2006}, url = {papers/Ferrari_PLoSBiol2006.pdf}} @article{Meltzoff:1990, Abstract = {This chapter began with a query about whether there was any content to an enterprise called "developmental cognitive science," and if so, whether the findings could inform work in adult cognition and neuropsychology. Both questions can now be answered in the affirmative. Evidence has been marshaled from infant studies concerning five topics of enduring interest in the cognitive and neuro-sciences: cross-modal integration, imitation, the coordination of perception and action, memory, and representation. The data show that young human infants can detect equivalences between information picked up by different sensory modalities. This was demonstrated both in tactual-visual perception of objects and auditory-visual perception of speech. Results also show that perception and production are intertwined literally from the earliest phases of infancy, with 4-month-olds demonstrating vocal imitation and newborns reproducing elementary gestures they saw an adult perform. There seems to be a transparency between the perceptual and motor systems, and it is conceivable that they may draw on the same internal code. Infants' proclivity to imitate was used to investigate early memory. It was found that young infants were not constrained to immediate mimicry, but could imitate after significant delays. The findings support the inference that infants, perhaps as early as birth, have a functioning memory system that cannot be reduced to "habit formation" or an exclusively "procedural memory." It was proposed instead that there is a kernel of some higher level memory system right from the earliest phases of human infancy. This does not imply that there is no development in the representational world of infants. Data were reviewed suggesting that there is a watershed transformation in childhood cognition at about 18 months of age. However, this is not a change from a stage in which there was a purely sensorimotor or habit-based system. Rather the development was characterized as a shift from using empirical or experience-based representations to using hypothetical representations, which concern possible realities. This developmental shift allows children to project into the future "what must be" and deduce from the past "what must have been," in advance of, and sometimes in the absence of, strictly perceptual evidence. This capacity provides the underpinnings for the conduct of science itself. Its origins are to be found in infancy.}, Author = {Meltzoff, A N}, Date-Added = {2011-09-14 12:09:05 -0400}, Date-Modified = {2011-09-14 12:13:26 -0400}, Journal = {Ann N Y Acad Sci}, Journal-Full = {Annals of the New York Academy of Sciences}, Keywords = {Learning; Memory; multisensory integration; function; Behavior; human; Infant; Newborn; neonatal; visual system; 21 Activity-development}, Mesh = {Aging; Auditory Perception; Child Development; Child, Preschool; Cognition; Conditioning (Psychology); Facial Expression; Humans; Imitative Behavior; Infant; Infant, Newborn; Language Development; Memory; Models, Neurological; Mouth; Neurosciences; Phonetics; Speech Perception; Touch; Visual Perception}, Pages = {1-31; discussion 31-7}, pmid = {2075949}, Pst = {ppublish}, Title = {Towards a developmental cognitive science. The implications of cross-modal matching and imitation for the development of representation and memory in infancy}, Volume = {608}, Year = {1990}, url = {papers/Meltzoff_AnnNYAcadSci1990.pdf}} @article{Beier:2011, Abstract = {To understand how the nervous system processes information, a map of the connections among neurons would be of great benefit. Here we describe the use of vesicular stomatitis virus (VSV) for tracing neuronal connections in vivo. We made VSV vectors that used glycoprotein (G) genes from several other viruses. The G protein from lymphocytic choriomeningitis virus endowed VSV with the ability to spread transsynaptically, specifically in an anterograde direction, whereas the rabies virus glycoprotein gave a specifically retrograde transsynaptic pattern. The use of an avian G protein fusion allowed specific targeting of cells expressing an avian receptor, which allowed a demonstration of monosynaptic anterograde tracing from defined cells. Synaptic connectivity of pairs of virally labeled cells was demonstrated by using slice cultures and electrophysiology. In vivo infections of several areas in the mouse brain led to the predicted patterns of spread for anterograde or retrograde tracers.}, Author = {Beier, Kevin T and Saunders, Arpiar and Oldenburg, Ian A and Miyamichi, Kazunari and Akhtar, Nazia and Luo, Liqun and Whelan, Sean P J and Sabatini, Bernardo and Cepko, Constance L}, Date-Added = {2011-09-14 11:28:50 -0400}, Date-Modified = {2011-09-14 11:30:41 -0400}, Doi = {10.1073/pnas.1110854108}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Vesicular stomatitis-Indiana virus; tracer; anterograde tracing; connectivity; connectome; Technique; ideas; Grants; Glycoproteins; Trans-synaptic; retrograde tracing; Genetic Engineering}, Month = {Aug}, pmid = {21825165}, Pst = {aheadofprint}, Title = {Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors}, Year = {2011}, url = {papers/Beier_ProcNatlAcadSciUSA2011.pdf}} @article{Greifzu:2011, Abstract = {We tested the influence of a photothrombotic lesion in somatosensory cortex on plasticity in the mouse visual system and the efficacy of anti-inflammatory treatment to rescue compromised learning. To challenge plasticity mechanisms, we induced monocular deprivation (MD) in 3-mo-old mice. In control animals, MD induced an increase of visual acuity of the open eye and an ocular dominance (OD) shift towards this eye. In contrast, after photothrombosis, there was neither an enhancement of visual acuity nor an OD-shift. However, OD-plasticity was present in the hemisphere contralateral to the lesion. Anti-inflammatory treatment restored sensory learning but not OD-plasticity, as did a 2-wk delay between photothrombosis and MD. We conclude that (i) both sensory learning and cortical plasticity are compromised in the surround of a cortical lesion; (ii) transient inflammation is responsible for impaired sensory learning, suggesting anti-inflammatory treatment as a useful adjuvant therapy to support rehabilitation following stroke; and (iii) OD-plasticity cannot be conceptualized solely as a local process because nonlocal influences are more important than previously assumed.}, Author = {Greifzu, Franziska and Schmidt, Silvio and Schmidt, Karl-Friedrich and Kreikemeier, Klaus and Witte, Otto W and L{\"o}wel, Siegrid}, Date-Added = {2011-09-14 11:00:58 -0400}, Date-Modified = {2011-09-14 11:02:39 -0400}, Doi = {10.1073/pnas.1016458108}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {visual system; neurological disorder; Stroke; Hypoxia-Ischemia; Somatosensory Cortex; visual cortex; sensory map; topographic map; Sensory Deprivation; Binocular; Monocular; plasticity; Inflammation; Immune System}, Month = {Aug}, pmid = {21873250}, Pst = {aheadofprint}, Title = {Global impairment and therapeutic restoration of visual plasticity mechanisms after a localized cortical stroke}, Year = {2011}, url = {papers/Greifzu_ProcNatlAcadSciUSA2011.pdf}} @article{Dang-Vu:2011, Abstract = {Humans are less responsive to the surrounding environment during sleep. However, the extent to which the human brain responds to external stimuli during sleep is uncertain. We used simultaneous EEG and functional MRI to characterize brain responses to tones during wakefulness and non-rapid eye movement (NREM) sleep. Sounds during wakefulness elicited responses in the thalamus and primary auditory cortex. These responses persisted in NREM sleep, except throughout spindles, during which they became less consistent. When sounds induced a K complex, activity in the auditory cortex was enhanced and responses in distant frontal areas were elicited, similar to the stereotypical pattern associated with slow oscillations. These data show that sound processing during NREM sleep is constrained by fundamental brain oscillatory modes (slow oscillations and spindles), which result in a complex interplay between spontaneous and induced brain activity. The distortion of sensory information at the thalamic level, especially during spindles, functionally isolates the cortex from the environment and might provide unique conditions favorable for off-line memory processing.}, Author = {Dang-Vu, Thien Thanh and Bonjean, Maxime and Schabus, Manuel and Boly, M{\'e}lanie and Darsaud, Annabelle and Desseilles, Martin and Degueldre, Christian and Balteau, Evelyne and Phillips, Christophe and Luxen, Andr{\'e} and Sejnowski, Terrence J and Maquet, Pierre}, Date-Added = {2011-09-14 10:54:26 -0400}, Date-Modified = {2011-09-14 10:55:48 -0400}, Doi = {10.1073/pnas.1112503108}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Sleep; oscillations; synchrony; neocortex; visual cortex; Stimulation; Auditory Cortex; Electroencephalography; function; human; fmri; Spontaneous activity}, Month = {Sep}, pmid = {21896732}, Pst = {aheadofprint}, Title = {Interplay between spontaneous and induced brain activity during human non-rapid eye movement sleep}, Year = {2011}, url = {papers/Dang-Vu_ProcNatlAcadSciUSA2011.pdf}} @article{Drager:1980, Abstract = {The extent of the binocular cortical field in albino mice, as revealed by recording from single cells, was almost normal; although the input from the ipsilateral eye was weaker than normal, most cells were driven from both eyes. By backfilling retinal ganglion cells from one optic tract with horseradish peroxidase we examined the origins of the retinofugal projections. Filled cells ipsilateral to the injected tract were concentrated in a crescent-shaped area bordering the inferior temperal retina. In black mice this area constituted 20\% of the total retinal area, in albinos 17\%. In black mice we counted nearly 1,000 labeled cells in the ipsilateral retina, or 2.6\% of all cells filled in both eyes. Albinos had about one-third fewer filled cells ipsilaterally than black mice. Four percent of all ipsilaterally filled cells in black mice and 8\% in albinos were scattered outside of the crescent region. The density of ipsilaterally projecting cells was uniform throughout the crescent region in black mice, but decreased toward the central retina in albinos. In retinas contralateral to the injection up to 39,000 cells were filled-about two-thirds of the cells in the ganglion-cell layer whose cytoplasm contained conspicuous Nissl substance. Depending on classification of unfilled cells as ganglion cells or interneurons, we estimated a total of 48,000 to 65,000 ganglion cells to exist in the retina. The size distribution of ipsilaterally projecting ganglion cells was similar in albinos and normals. Ipsilaterally projecting ganglion cells were on average 1.8-3 times larger in volume than contralaterally projecting ones in both types of mice. Displaced ganglion cells were relatively more common in ipsilateral retinofugal projections: 21\% of all ipsilateral ganglion cells were displaced versus less than 1\% of all the contralateral ganglion cells in black mice. In albinos only 13\% of the ganglion cells in the ipsilateral retina were displaced. The overall reduction in ipsilaterally projecting cells in albinos was reflected twice as much in displaced ganglion cells as in normally placed ones.}, Author = {Dr{\"a}ger, U C and Olsen, J F}, Date-Added = {2011-09-13 17:46:06 -0400}, Date-Modified = {2011-09-14 10:54:08 -0400}, Doi = {10.1002/cne.901910306}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {mice; visual system; retina; connectivity; Albinism; projection; Retinal Ganglion Cells; structural remodeling; Structure-Activity Relationship; Binocular; Monocular; topographic map; sensory map; retinotopy; Classical/physiology}, Mesh = {Animals; Dominance, Cerebral; Mice; Mice, Inbred C57BL; Neurons; Optic Nerve; Retina; Visual Cortex; Visual Pathways}, Month = {Jun}, Number = {3}, Pages = {383-412}, pmid = {7410600}, Pst = {ppublish}, Title = {Origins of crossed and uncrossed retinal projections in pigmented and albino mice}, Volume = {191}, Year = {1980}, url = {papers/Dräger_JCompNeurol1980.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901910306}} @article{Sahraie:1997, Abstract = {Following striate cortex damage in monkeys and humans there can be residual function mediated by parallel visual pathways. In humans this can sometimes be associated with a "feeling" that something has happened, especially with rapid movement or abrupt onset. For less transient events, discriminative performance may still be well above chance even when the subject reports no conscious awareness of the stimulus. In a previous study we examined parameters that yield good residual visual performance in the "blind" hemifield of a subject with unilateral damage to the primary visual cortex. With appropriate parameters we demonstrated good discriminative performance, both with and without conscious awareness of a visual event. These observations raise the possibility of imaging the brain activity generated in the "aware" and the "unaware" modes, with matched levels of discrimination performance, and hence of revealing patterns of brain activation associated with visual awareness. The intact hemifield also allows a comparison with normal vision. Here we report the results of a functional magnetic resonance imaging study on the same subject carried out under aware and unaware stimulus conditions. The results point to a shift in the pattern of activity from neocortex in the aware mode, to subcortical structures in the unaware mode. In the aware mode prestriate and dorsolateral prefrontal cortices (area 46) are active. In the unaware mode the superior colliculus is active, together with medial and orbital prefrontal cortical sites.}, Author = {Sahraie, A and Weiskrantz, L and Barbur, J L and Simmons, A and Williams, S C and Brammer, M J}, Date-Added = {2011-09-13 17:18:36 -0400}, Date-Modified = {2011-09-13 17:19:35 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {retina; human; visual system; optic tectum; Superior Colliculus; Structure-Activity Relationship; 21 Activity-development; retinotopy; sensory map; topographic map; bilateral; mirror symmetry; visual cortex; blindsight}, Mesh = {Brain; Humans; Magnetic Resonance Imaging; Visual Pathways}, Month = {Aug}, Number = {17}, Pages = {9406-11}, Pmc = {PMC23203}, pmid = {9256495}, Pst = {ppublish}, Title = {Pattern of neuronal activity associated with conscious and unconscious processing of visual signals}, Volume = {94}, Year = {1997}, url = {papers/Sahraie_ProcNatlAcadSciUSA1997.pdf}} @article{Rajimehr:2009, Abstract = {In humans and other Old World primates, much of visual cortex comprises a set of retinotopic maps, embedded in a cortical sheet with well known, identifiable folding patterns. However, the relationship between these two prominent cortical variables has not been comprehensively studied. Here, we quantitatively tested this relationship using functional and structural magnetic resonance imaging in monkeys and humans. We found that the vertical meridian of the visual field tends to be represented on gyri (convex folds), whereas the horizontal meridian is preferentially represented in sulci (concave folds), throughout visual cortex in both primate species. This relationship suggests that the retinotopic maps may constrain the pattern of cortical folding during development.}, Author = {Rajimehr, Reza and Tootell, Roger B H}, Date-Added = {2011-09-13 17:08:47 -0400}, Date-Modified = {2011-09-13 17:17:21 -0400}, Doi = {10.1523/JNEUROSCI.1835-09.2009}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retina; connectivity; projection; human; monkey; visual system; optic tectum; Structure-Activity Relationship; 21 Activity-development; retinotopy; sensory map; topographic map; bilateral; mirror symmetry}, Mesh = {Animals; Brain Mapping; Humans; Macaca mulatta; Magnetic Resonance Imaging; Photic Stimulation; Retina; Species Specificity; Visual Cortex}, Month = {Sep}, Number = {36}, Pages = {11149-52}, Pmc = {PMC2785715}, pmid = {19741121}, Pst = {ppublish}, Title = {Does retinotopy influence cortical folding in primate visual cortex?}, Volume = {29}, Year = {2009}, url = {papers/Rajimehr_JNeurosci2009.pdf}} @article{Thanos:1999, Abstract = {Unilateral intraocular injections of either of two fluorescent carbocyanine dyes into the embryonic chick eye resulted in both retrograde staining of ganglion cells (GCs) in the eye contralateral to site of injection and anterograde labeling of axons whose cell bodies were located within the injected eye. This prominent retino-retinal projection formed by thousands of GCs having a nasal origin and temporal termination appeared at embryonic day 6 (E6), attained its maximum intensity at E13-E14, and gradually disappeared until E18. The axonal growth cones ended superficially and never penetrated deeper layers of the retina. Treatment of the projection with BDNF resulted in massive terminal branching of the axons within deeper layers of the target retina. Double injection into the eye and the isthmo-optic nucleus showed a concomitant ingrowth of axons in the contralateral retina. Individual GCs died between E9 and E13, but massive apoptotic cell death was mainly monitored at E14 and later. Disintegrated cells showed typical images of apoptosis. Because degenerating cells were prelabeled with the membranophilic fluorescent carbocyanine dye, their death allowed the concomitant visualization of phagocytosing cells, too. Radial M{\"u}ller glia were the only class of cells observed to become phagocytotic between E9 and E16. These cells became replaced exclusively with microglial cells from E17 on. The results suggest that the topologically restricted retino-retinal projection may have some developmental significance rather than representing a massive erroneous projection. Most likely, the projection may serve as a "template" to guide centrifugal isthmo-optic axons into the retina.}, Author = {Thanos, S}, Date-Added = {2011-09-13 17:04:16 -0400}, Date-Modified = {2011-09-13 17:07:05 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retina; connectivity; retinopetal; retino-retino; projection; Chick Embryo; visual system; optic tectum; Structure-Activity Relationship; 21 Activity-development; retinotopy; sensory map; topographic map; bilateral; mirror symmetry}, Mesh = {Animals; Apoptosis; Brain-Derived Neurotrophic Factor; Chick Embryo; Eye; Nerve Fibers; Nerve Growth Factors; Reproducibility of Results; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways}, Month = {May}, Number = {10}, Pages = {3900-17}, pmid = {10234021}, Pst = {ppublish}, Title = {Genesis, neurotrophin responsiveness, and apoptosis of a pronounced direct connection between the two eyes of the chick embryo: a natural error or a meaningful developmental event?}, Volume = {19}, Year = {1999}, url = {papers/Thanos_JNeurosci1999.pdf}} @article{Takahashi:2007a, Abstract = {The functional roles of commissural excitation and inhibition between the two superior colliculi (SCs) are not yet well understood. We previously showed the existence of strong excitatory commissural connections between the rostral SCs, although commissural connections had been considered to be mainly inhibitory. In this study, by recording intracellular potentials, we examined the topographical distribution of commissural monosynaptic excitation and inhibition from the contralateral medial and lateral SC to tectoreticular neurons (TRNs) in the medial or lateral SC of anesthetized cats. About 85\% of TRNs examined projected to both the ipsilateral Forel's field H and the contralateral inhibitory burst neuron region where the respective premotor neurons for vertical and horizontal saccades reside. Medial TRNs received strong commissural excitation from the medial part of the opposite SC, whereas lateral TRNs received excitation mainly from its lateral part. Injection of wheat germ agglutinin-horseradish peroxidase into the lateral or medial SC retrogradely labeled many larger neurons in the lateral or medial part of the contralateral SC, respectively. These results indicated that excitatory commissural connections exist between the medial and medial parts and between the lateral and lateral parts of the rostral SCs. These may play an important role in reinforcing the conjugacy of upward and downward saccades, respectively. In contrast, medial SC projections to lateral SC TRNs and lateral SC projections to medial TRNs mainly produce strong inhibition. This shows that regions representing upward saccades inhibit contralateral regions representing downward saccades and vice versa.}, Author = {Takahashi, M and Sugiuchi, Y and Shinoda, Y}, Date-Added = {2011-09-13 17:02:53 -0400}, Date-Modified = {2011-09-16 10:47:22 -0400}, Doi = {10.1152/jn.00696.2007}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Superior Colliculus; bilateral; mirror symmetry; optic tectum; connectivity; Structure-Activity Relationship; function; cat; excitatory; inhibitory; GABA; blindsight; visual system; sensory map; topographic map}, Mesh = {Action Potentials; Animals; Brain Mapping; Cats; Dose-Response Relationship, Radiation; Electric Stimulation; Eye Movements; Functional Laterality; Models, Biological; Neural Inhibition; Neural Pathways; Neurons; Reaction Time; Superior Colliculi; Synaptic Transmission; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate}, Month = {Nov}, Number = {5}, Pages = {2664-82}, pmid = {17728384}, Pst = {ppublish}, Title = {Commissural mirror-symmetric excitation and reciprocal inhibition between the two superior colliculi and their roles in vertical and horizontal eye movements}, Volume = {98}, Year = {2007}, url = {papers/Takahashi_JNeurophysiol2007.pdf}} @article{Takahashi:2010a, Abstract = {Our electrophysiological study showed that there are topographic connections between excitatory and inhibitory commissural neurons (CNs) in one superior colliculus (SC) and tectoreticular neurons (TRNs) in the opposite SC. To obtain morphological evidence for these topographic commissural connections between the SCs, tracers were injected into various parts of the SC, the inhibitory burst neuron (IBN) area and Forel's field H (FFH), in the cat. Retrogradely labeled CNs were classified into three types according to their somatic areas and identified as GABA-positive or -negative immunohistochemically. Caudal SC injections labeled small GABA-positive CNs (<200 μm(2)) in the deep layers of the opposite rostral SC. Rostral SC injections mainly labeled medium-sized GABA-negative CNs (200-700 μm(2)) in the upper intermediate layer of the opposite rostral SC and small GABA-positive CNs in its deeper layers. Lateral SC injections labeled small GABA-positive CNs in the opposite medial SC and mainly medium-sized GABA-negative CNs in its lateral part. Medial SC injections labeled small GABA-positive CNs in the lateral SC and medium-sized GABA-negative CNs in the medial SC. In comparison, TRNs projecting to the FFH or IBN region were large (>700 μm(2)) and medium-sized. Many of the medium-sized GABA-negative CNs were TRNs projecting to the FFH. These results indicate that mirror-symmetric excitatory pathways link medial to medial (upper field) and lateral to lateral (lower field) parts of the SCs, whereas upper and lower field representations are linked by reciprocal inhibitory pathways in the tectal commissure. These connections presumably play important roles in conjugate upward and downward vertical saccades.}, Author = {Takahashi, M and Sugiuchi, Y and Shinoda, Y}, Date-Added = {2011-09-13 17:00:30 -0400}, Date-Modified = {2011-09-16 10:47:10 -0400}, Doi = {10.1152/jn.00554.2010}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Superior Colliculus; bilateral; mirror symmetry; optic tectum; connectivity; Structure-Activity Relationship; function; cat; excitatory; inhibitory; GABA; blindsight; visual system; sensory map; topographic map}, Mesh = {Animals; Cats; Dominance, Cerebral; Excitatory Postsynaptic Potentials; Immunohistochemistry; Inhibitory Postsynaptic Potentials; Nerve Net; Neurons; Saccades; Superior Colliculi; Synapses; Synaptic Transmission; gamma-Aminobutyric Acid}, Month = {Dec}, Number = {6}, Pages = {3146-67}, pmid = {20926614}, Pst = {ppublish}, Title = {Topographic organization of excitatory and inhibitory commissural connections in the superior colliculi and their functional roles in saccade generation}, Volume = {104}, Year = {2010}, url = {papers/Takahashi_JNeurophysiol2010.pdf}} @article{Tognini:2011, Abstract = {miR-132 is a CREB-induced microRNA that is involved in dendritic spine plasticity. We found that visual experience regulated histone post-translational modifications at a CRE locus that is important for miR-212 and miR-132 cluster transcription, and regulated miR-132 expression in the visual cortex of juvenile mice. Monocular deprivation reduced miR-132 expression in the cortex contralateral to the deprived eye. Counteracting this miR-132 reduction with an infusion of chemically modified miR-132 mimic oligonucleotides completely blocked ocular dominance plasticity.}, Author = {Tognini, Paola and Putignano, Elena and Coatti, Alessandro and Pizzorusso, Tommaso}, Date-Added = {2011-09-13 10:03:32 -0400}, Date-Modified = {2011-09-13 10:03:40 -0400}, Doi = {10.1038/nn.2920}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Sensory Deprivation; Structure-Activity Relationship; structural remodeling; microRNAs; 21 Activity-development; visual cortex; visual system; topographic map; sensory map; Binocular; Monocular}, Month = {Sep}, pmid = {21892154}, Pst = {aheadofprint}, Title = {Experience-dependent expression of miR-132 regulates ocular dominance plasticity}, Year = {2011}, url = {papers/Tognini_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2920}} @article{Mellios:2011, Abstract = {Using quantitative analyses, we identified microRNAs (miRNAs) that were abundantly expressed in visual cortex and that responded to dark rearing and/or monocular deprivation. The most substantially altered miRNA, miR-132, was rapidly upregulated after eye opening and was delayed by dark rearing. In vivo inhibition of miR-132 in mice prevented ocular dominance plasticity in identified neurons following monocular deprivation and affected the maturation of dendritic spines, demonstrating its critical role in the plasticity of visual cortex circuits.}, Author = {Mellios, Nikolaos and Sugihara, Hiroki and Castro, Jorge and Banerjee, Abhishek and Le, Chuong and Kumar, Arooshi and Crawford, Benjamin and Strathmann, Julia and Tropea, Daniela and Levine, Stuart S and Edbauer, Dieter and Sur, Mriganka}, Date-Added = {2011-09-13 10:00:54 -0400}, Date-Modified = {2011-09-13 10:02:15 -0400}, Doi = {10.1038/nn.2909}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Sensory Deprivation; Structure-Activity Relationship; structural remodeling; microRNAs; 21 Activity-development; visual cortex; visual system; topographic map; sensory map; Binocular; Monocular}, Month = {Sep}, pmid = {21892155}, Pst = {aheadofprint}, Title = {miR-132, an experience-dependent microRNA, is essential for visual cortex plasticity}, Year = {2011}, url = {papers/Mellios_NatNeurosci2011.pdf}, Bdsk-File-2 = {papers/Mellios_NatNeurosci2011a.pdf}} @article{Olavarria:1996, Abstract = {In the cat, callosal connections in area 17 are largely confined to a 5-6-mm-wide strip at the 17/18 border. It is commonly thought that callosal fibers extending from between the 17/18 border regions interconnect loci that are mirror-symmetric with respect to the midline of the brain, but this idea has not been tested experimentally. The present study examined the organization of callosal linkages in the 17/18 border region of normal adult cats by analyzing the patterns of connections revealed in one hemisphere after small injections of different fluorescent tracers into the opposite 17/18 callosal region. The location of the injection sites within areas 17 and 18 was assessed by examining architectonic data and by inspecting the labeling pattern in the ipsilateral visual thalamus. Area 17 and 18 were separated by a 1-1.5-mm-wide zone of cytoarchitectonic transition rather than by a sharp border. The results show that, in general, callosal fibers interconnect loci that are not mirror-symmetric with respect to the midline. Thus, area 17 injections placed nearly 3 mm away from the 17/18 transition zone produced discrete labeled areas located preferentially within the contralateral 17/18 transition zone. However, when the injection site was within the 17/18 transition zone, labeled cells were found primarily medial and lateral to, but not within, the 17/18 transition zone in the contralateral hemisphere. Previous studies have indicated that the 17/18 transition zone contains a representation of a strip of the ipsilateral visual field. Comparison of the retinotopy of the 17/18 border region with the mirror-reversed pattern of callosal linkages found in the present study suggests that callosal fibers link points that are in retinotopic correspondence in both hemispheres.}, Author = {Olavarria, J F}, Date-Added = {2011-09-13 09:29:00 -0400}, Date-Modified = {2011-09-13 09:29:11 -0400}, Doi = {10.1002/(SICI)1096-9861(19960318)366:4\<643::AID-CNE6\>3.0.CO;2-4}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Activity-development; visual cortex; visual system; retina; sensory map; topographic map; synapse formation; Structure-Activity Relationship; structural remodeling; bilateral; mirror symmetry; connectivity;}, Mesh = {Animals; Brain Mapping; Cats; Corpus Callosum; Functional Laterality; Nerve Fibers; Rats; Retina; Visual Cortex; Visual Fields; Visual Pathways}, Month = {Mar}, Number = {4}, Pages = {643-55}, pmid = {8833114}, Pst = {ppublish}, Title = {Non-mirror-symmetric patterns of callosal linkages in areas 17 and 18 in cat visual cortex}, Volume = {366}, Year = {1996}, url = {papers/Olavarria_JCompNeurol1996.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1096-9861(19960318)366:4%5C<643::AID-CNE6%5C>3.0.CO;2-4}} @article{Olavarria:2003, Abstract = {Studies of callosal projections in striate cortex show that the retina is involved in the development of topographical connections. In normal animals callosal fibers connect retinotopically corresponding, nonmirror-symmetric cortical loci, whereas in animals bilaterally enucleated at birth, callosal fibers connect topographically mismatched, mirror-symmetric loci. Moreover, in rodents the overall pattern of visual callosal connections is adult-like by postnatal day 12 (P12). In this study we delayed the onset of retinal deafferentation in rats and mice in order to determine the period when retinal influences are critically needed for the development of retinotopically matched callosal linkages. Callosal maps were revealed by placing small injections of retrogradely and anterogradely transported tracers into different loci of lateral striate cortex. We found that the patterns of callosal linkages in rats enucleated at P12, P8, and P6 were nonmirror-symmetric, as in normally reared rats. In contrast, the patterns of linkages in rats enucleated at P4 closely resembled the mirror-symmetric pattern seen in rats enucleated at birth (P0). A similar reversal in topography (from symmetric to nonsymmetric) occurred in mice when enucleation was delayed from P4 to P6. These findings indicate that retinal input prior to P6, but not prior to P4, is sufficient for specifying normal callosal topography. Moreover, they suggest that development of retinotopically matched callosal linkages depends critically on retinal influences during a brief period between P4 and P6, when callosal connections are still very immature.}, Author = {Olavarria, Jaime F and Hiroi, Ryoko}, Date-Added = {2011-09-13 09:26:35 -0400}, Date-Modified = {2011-09-13 09:28:31 -0400}, Doi = {10.1002/cne.10615}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Activity-development; visual cortex; visual system; retina; sensory map; topographic map; synapse formation; Structure-Activity Relationship; structural remodeling; bilateral; mirror symmetry; connectivity;}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Corpus Callosum; Eye Enucleation; Female; Mice; Mice, Inbred C57BL; Neural Pathways; Pregnancy; Rats; Rats, Long-Evans; Retina; Visual Cortex; Visual Fields}, Month = {Apr}, Number = {2}, Pages = {156-72}, pmid = {12640667}, Pst = {ppublish}, Title = {Retinal influences specify cortico-cortical maps by postnatal day six in rats and mice}, Volume = {459}, Year = {2003}, url = {papers/Olavarria_JCompNeurol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10615}} @article{Sengpiel:2002, Abstract = {Neuronal activity is important for both the initial formation and the subsequent refinement of anatomical and physiological features of the mammalian visual system. Here we examine recent evidence concerning the role that spontaneous activity plays in axonal segregation, both of retinogeniculate afferents into eye-specific layers and of geniculocortical afferents into ocular dominance bands. We also assess the role of activity in the generation and plasticity of orientation selectivity in the primary visual cortex. Finally, we review recent challenges to textbook views on how inputs representing the two eyes interact during the critical period of visual cortical plasticity.}, Author = {Sengpiel, Frank and Kind, Peter C}, Date-Added = {2011-09-13 09:09:57 -0400}, Date-Modified = {2011-09-13 09:11:32 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {retinal wave paper; 21 Activity-development; structural remodeling; Structure-Activity Relationship; connectivity; plasticity; visual cortex; visual system; retina; Spontaneous activity; topographic map; sensory map; Sensory Deprivation; activity manipulation; review; optic tectum; Superior Colliculus; LGN}, Mesh = {Aging; Animals; Brain; Embryonic and Fetal Development; Ferrets; Motor Activity; Neurons; Retina; Visual Perception}, Month = {Dec}, Number = {23}, Pages = {R818-26}, pmid = {12477410}, Pst = {ppublish}, Title = {The role of activity in development of the visual system}, Volume = {12}, Year = {2002}, url = {papers/Sengpiel_CurrBiol2002.pdf}} @article{Berns:1993, Abstract = {Neurons in the visual cortex require correlated binocular activity during a critical period early in life to develop normal response properties. We present a model for how the disparity selectivity of cortical neurons might arise during development. The model is based on Hebbian mechanisms for plasticity at synapses between geniculocortical neurons and cortical cells. The model is driven by correlated activity in retinal ganglion cells within each eye before birth and additionally between eyes after birth. With no correlations present between the eyes, the cortical model developed only monocular cells. Adding a small amount of correlation between eyes at the beginning of development produced cortical neurons that were entirely binocular and tuned to zero disparity. However, if an initial phase of purely same-eye correlations was followed by a second phase of development that included correlations between eyes, the cortical model became populated with both monocular and binocular cells. Moreover, in the two-phase model, binocular cells tended to be selective for zero disparity, whereas the more monocular cells tended to have nonzero disparity. This relationship between ocular dominance and disparity has been observed in the visual cortex of the cat by other workers. Differences in the relative timing of the two developmental phases could account for the higher proportion of monocular cells found in the visual cortices of other animals.}, Author = {Berns, G S and Dayan, P and Sejnowski, T J}, Date-Added = {2011-09-13 08:35:06 -0400}, Date-Modified = {2011-09-13 08:37:53 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Theoretical; Models; Computational Biology; retinal wave paper; Retina; visual cortex; visual system; sensory map; topographic map; hebbian; synapse formation; Structure-Activity Relationship; 21 Activity-development; structural remodeling; mirror symmetry; bilateral}, Mesh = {Aging; Animals; Embryonic and Fetal Development; Eye; Functional Laterality; Mathematics; Models, Neurological; Neurons; Ocular Physiological Phenomena; Retina; Visual Cortex; Visual Perception}, Month = {Sep}, Number = {17}, Pages = {8277-81}, Pmc = {PMC47332}, pmid = {8367493}, Pst = {ppublish}, Title = {A correlational model for the development of disparity selectivity in visual cortex that depends on prenatal and postnatal phases}, Volume = {90}, Year = {1993}, url = {papers/Berns_ProcNatlAcadSciUSA1993.pdf}} @article{Voss:2011, Author = {Voss, Patrice}, Date-Added = {2011-09-12 14:07:29 -0400}, Date-Modified = {2011-09-12 14:09:09 -0400}, Doi = {10.1523/JNEUROSCI.2624-11.2011}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {optic tectum; Superior Colliculus; blindsight; Blindness; Human; Visual Cortex; pulvinar; Sensory Deprivation; sensory map; review; Grants; ideas; neurological disorder}, Month = {Aug}, Number = {33}, Pages = {11745-7}, pmid = {21849534}, Pst = {ppublish}, Title = {Superior tactile abilities in the blind: is blindness required?}, Volume = {31}, Year = {2011}, url = {papers/Voss_JNeurosci2011.pdf}} @article{Fagiolini:1994, Abstract = {Postnatal development of rat visual cortical functions was studied by recording extracellularly from the primary visual cortex of 22 animals ranging in age from postnatal day 17 (P17) to P45. We found that in the youngest animals (P17-P19) all visual cortical functions tested were immature. Selectivity for orientation and movement direction of visual stimuli was almost absent, most cells received binocular input and their mean receptive field size was 5-6 times the adult size. Visual acuity was half its adult value. These functional properties developed gradually during the following weeks and by P45 they were all adult-like. This functional development is affected by manipulations of the visual input such as dark rearing (DR) and monocular deprivation (MD). DR prevented the normal postnatal maturation of visual cortical functions: in P60 rats, dark reared from birth, their visual cortical functions resembled those of P19-P21 rats. MD from P15 to P45 resulted in a dramatic shift of the ocular dominance distribution (ODD) in favour of the open eye and in a loss of visual acuity for the deprived eye. To determine the sensitive period of rat visual cortex to MD (critical period) we evaluated the shift in ODD of visual cortical neurones in rats that were subjected to the progressive delay of the onset of fixed MD period (10 days). Our results show that the critical period begins around the end of the third postnatal week, peaks between the fourth and fifth week and starts to decline from the end of the fifth week.}, Author = {Fagiolini, M and Pizzorusso, T and Berardi, N and Domenici, L and Maffei, L}, Date-Added = {2011-09-12 10:45:28 -0400}, Date-Modified = {2011-09-12 10:48:30 -0400}, Journal = {Vision Res}, Journal-Full = {Vision research}, Keywords = {Sensory Deprivation; sensory map; Visual Cortex; visual system; 21 Activity-development; 21 Neurophysiology; rat; activity manipulation; retina; retinotopy; topographic map}, Mesh = {Age Factors; Animals; Animals, Newborn; Brain Mapping; Darkness; Evoked Potentials, Visual; Rats; Rotation; Sensory Deprivation; Vision, Binocular; Visual Acuity; Visual Cortex}, Month = {Mar}, Number = {6}, Pages = {709-20}, pmid = {8160387}, Pst = {ppublish}, Title = {Functional postnatal development of the rat primary visual cortex and the role of visual experience: dark rearing and monocular deprivation}, Volume = {34}, Year = {1994}, url = {papers/Fagiolini_VisionRes1994.pdf}} @article{Olavarria:2006, Abstract = {In normal rats callosal projections in striate cortex connect retinotopically corresponding, nonmirror-symmetric cortical loci, whereas in rats bilaterally enucleated at birth, callosal fibers connect topographically mismatched, mirror-symmetric loci. Moreover, retina input specifies the topography of callosal projections by postnatal day (P)6. To investigate whether retinal input guides development of callosal maps by promoting either the corrective pruning of exuberant axon branches or the specific ingrowth and elaboration of axon branches at topographically correct places, we studied the topography of emerging callosal connections at and immediately after P6. After restricted intracortical injections of anterogradely and retrogradely transported tracers we observed that the normal, nonmirror-symmetric callosal map, as well as the anomalous, mirror-symmetric map observed in neonatally enucleated animals, are present by P6-7, just as collateral branches of simple architecture emerge from their parental axons and grow into superficial cortical layers. Our results therefore do not support the idea that retinal input guides callosal map formation by primarily promoting the large-scale elimination of long, nontopographic branches and arbors. Instead, they suggest that retinal input specifies the sites on the parental axons from which interstitial branches will grow to invade middle and upper cortical layers, thereby ensuring that the location of invading interstitial branches is accurately related to the topographical location of the soma that gives rise to the parental axon. Moreover, our results from enucleated rats suggest that the cues that determine the mirror-symmetric callosal map exert only a weak control on the topography of fiber ingrowth.}, Author = {Olavarria, Jaime F and Safaeian, Pegah}, Date-Added = {2011-09-12 10:39:22 -0400}, Date-Modified = {2011-09-13 08:34:14 -0400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {retinal wave paper; retina; rat; Spontaneous activity; 21 Activity-development; visual cortex; sensory map; topographic map; Embryo and Fetal Development; visual system; 21 Neurophysiology; bilateral; synapse formation; activity manipulation;; mirror symmetry}, Mesh = {Animals; Brain Mapping; Corpus Callosum; Eye Enucleation; Functional Laterality; Nerve Fibers; Rats; Rats, Long-Evans; Retina; Visual Cortex; Visual Pathways}, Month = {Jun}, Number = {4}, Pages = {495-512}, Pmc = {PMC2577613}, pmid = {16572463}, Pst = {ppublish}, Title = {Development of callosal topography in visual cortex of normal and enucleated rats}, Volume = {496}, Year = {2006}, url = {papers/Olavarria_JCompNeurol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20938}} @article{Adams:2003, Author = {Adams, Daniel L and Horton, Jonathan C}, Date-Added = {2011-09-12 10:37:40 -0400}, Date-Modified = {2011-09-13 08:34:14 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {retinal wave paper; retina; monkey; Spontaneous activity; 21 Activity-development; visual cortex; sensory map; topographic map; Embryo and Fetal Development; visual system; bilateral; synapse formation; Neocortex; mirror symmetry}, Mesh = {Animals; Cell Differentiation; Dominance, Ocular; Electron Transport Complex IV; Genetic Variation; Neural Pathways; Neurons; Phenotype; Saimiri; Visual Cortex; Visual Perception}, Month = {Feb}, Number = {2}, Pages = {113-4}, pmid = {12536211}, Pst = {ppublish}, Title = {Capricious expression of cortical columns in the primate brain}, Volume = {6}, Year = {2003}, url = {papers/Adams_NatNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1004}} @article{Warland:2006, Abstract = {Correlated spontaneous activity in the form of retinal "waves" has been observed in a wide variety of developing animals, but whether retinal waves occur in the primate has not been determined previously. To address this issue, we recorded from isolated retinas using multielectrode arrays at six fetal ages: embryonic day 51 (E51), E55, E60, E67, E71, and E76. These recordings revealed that the fetal monkey retina is essentially silent at E51 and E55, with only few cells firing on rare occasions and without any obvious spatial or temporal order. Because previous work has shown that the magnocellular and parvocellular subdivisions of the dorsal lateral geniculate are selectively innervated during this early period, our results suggest that this process is unlikely to be regulated by retinal activity. Highly structured retinal waves were first observed at E60, >1 week before the segregation of eye-specific retinal dorsal lateral geniculate nucleus projections commences. The incidence of such waves decreased rapidly and progressively during the developmental period (E67-E76) when segregated eye-specific projections become established. Our findings indicate that retinal waves first occur in the fetal monkey at a remarkably early stage of development, >100 d before birth, and that this activity undergoes rapid changes in salient properties when eye-specific retinogeniculate projections are being formed.}, Author = {Warland, David K and Huberman, Andrew D and Chalupa, Leo M}, Date-Added = {2011-09-12 10:35:18 -0400}, Date-Modified = {2011-09-13 08:34:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {currOpinRvw; retinal wave paper; retina; monkey; Spontaneous activity; 21 Activity-development; visual cortex; sensory map; topographic map; Embryo and Fetal Development; visual system; 21 Neurophysiology; bilateral; synapse formation; mirror symmetry}, Mesh = {Action Potentials; Animals; Biological Clocks; Geniculate Bodies; Macaca fascicularis; Retina; Species Specificity; Visual Pathways}, Month = {May}, Number = {19}, Pages = {5190-7}, pmid = {16687510}, Pst = {ppublish}, Title = {Dynamics of spontaneous activity in the fetal macaque retina during development of retinogeniculate pathways}, Volume = {26}, Year = {2006}, url = {papers/Warland_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0328-06.2006}} @article{Phillips:2011, Abstract = {The mechanisms by which experience guides refinement of converging afferent pathways are poorly understood. We describe a vision-driven refinement of corticocollicular inputs that determines the consolidation of retinal and visual cortical (VC) synapses on individual neurons in the superficial superior colliculus (sSC). Highly refined corticocollicular terminals form 1-2 days after eye-opening (EO), accompanied by VC-dependent filopodia sprouting on proximal dendrites, and PSD-95 and VC-dependent quadrupling of functional synapses. Delayed EO eliminates synapses, corticocollicular terminals, and spines on VC-recipient dendrites. Awake recordings after EO show that VC and retina cooperate to activate sSC neurons, and VC light responses precede sSC responses within intervals promoting potentiation. Eyelid closure is associated with more protracted cortical visual responses, causing the majority of VC spikes to follow those of the colliculus. These data implicate spike-timing plasticity as a mechanism for cortical input survival, and support a cooperative strategy for retinal and cortical coinnervation of the sSC.}, Author = {Phillips, Marnie A and Colonnese, Matthew T and Goldberg, Julie and Lewis, Laura D and Brown, Emery N and Constantine-Paton, Martha}, Date-Added = {2011-09-12 10:31:34 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {currOpinRvw; optic tectum; Superior Colliculus; visual cortex; retina; visual system; Efferent Pathways; Cooperative Behavior; oscillations; synchrony; plasticity; 21 Activity-development; Electrophysiology; 21 Neurophysiology; synapse formation; retinal wave paper; Mouse}, Month = {Aug}, Number = {4}, Pages = {710-24}, pmid = {21867886}, Pst = {ppublish}, Title = {A synaptic strategy for consolidation of convergent visuotopic maps}, Volume = {71}, Year = {2011}, url = {papers/Phillips_Neuron2011.pdf}, Bdsk-File-2 = {papers/Phillips_Neuron2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.06.023}} @article{Xu:2011a, Abstract = {The functional properties of neural circuits become increasingly robust over development. This allows circuits to optimize their output in response to a variety of input. However, it is not clear whether this optimization is a function of hardwired circuit elements, or whether it requires neural experience to develop. We performed rapid in vivo imaging of calcium signals from bulk-labeled neurons in the Xenopus laevis optic tectum to resolve the rapid spatiotemporal response properties of populations of developing tectal neurons in response to visual stimuli. We found that during a critical time in tectal development, network activity becomes increasingly robust, more correlated, and more synchronous. These developmental changes require normal visual input during development and are disrupted by NMDAR blockade. Our data show that visual activity and NMDAR activation are critical for the maturation of tectal network dynamics during visual system development.}, Author = {Xu, Heng and Khakhalin, Arseny S and Nurmikko, Arto V and Aizenman, Carlos D}, Date-Added = {2011-09-12 10:22:26 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {optic tectum; Superior Colliculus; calcium imaging; optical physiology; Methods; Technique; retinal wave paper; 21 Activity-development; oscillations; synchrony; N-Methyl-D-Aspartate/agonists/antagonists; NMDA}, Mesh = {Animals; Calcium; Dizocilpine Maleate; Molecular Imaging; Neural Networks (Computer); Neurons; Photic Stimulation; Receptors, N-Methyl-D-Aspartate; Superior Colliculi; Visual Pathways; Visual Perception; Xenopus laevis}, Month = {Jun}, Number = {22}, Pages = {8025-36}, Pmc = {PMC3169172}, pmid = {21632924}, Pst = {ppublish}, Title = {Visual experience-dependent maturation of correlated neuronal activity patterns in a developing visual system}, Volume = {31}, Year = {2011}, url = {papers/Xu_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5802-10.2011}} @article{Wagor:1980, Abstract = {Detailed retinotopic maps of primary visual cortex (area 17) and the extrastriate visual regions surrounding it (areas 18a and 18b) have been constructed for the C57BL/6J mouse using standard electrophysiological mapping techniques. Primary visual cortex (area 17), as defined cytoarchitectonically, contains one complete representation of the contralateral visual field, termed V1, in which azimuth and elevation lines are approximately orthogonal. The upper visual field is represented caudally and the nasal field laterally. Binocular cells are encountered in the cortical representation of the nasal 30--40 degrees of the visual field, and there is an expanded representation of the nasal field. Extrastriate visual cortex of the mouse, like that of other mammals, contains multiple representations of the visual field. The cytoarchitectonic region of cortex lateral and rostral to area 17, termed area 18a, contains at least two such representations. The more medial of these, which by convention we have called V2, is a narrow strip surrounding V1 on its lateral and rostral aspects; the vertical meridian lies along a portion of its common border with V1. The visual field representation in V2 is not a mirror image of that in V1; the representation of the horizontal meridian forms the lateral border of V2, and the visual field representation is split so that adjacent points on either side of the horizontal meridian are represented in nonadjacent parts of V2. The other visual field representation within area 18a, which we have termed V3, is a small but apparently complete representation that lies lateral to V2. The visual field representations medial to area 17 correspond to cytoarchitectonic area 18b. Area 18b contains two representations of the temporal visual field that we have labeled Vm-r and Vm-c, and contains little or no representation of the most nasal aspect of the field.}, Author = {Wagor, E and Mangini, N J and Pearlman, A L}, Date-Added = {2011-09-09 17:03:45 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {visual system; visual cortex; mouse; retinotopy; topographic map; behavior; sensory map; vision; retina; retinal wave paper}, Mesh = {Animals; Brain Mapping; Cats; Eye Movements; Haplorhini; Mice; Mice, Inbred C57BL; Rabbits; Retina; Rodentia; Sciuridae; Species Specificity; Thalamic Nuclei; Visual Cortex; Visual Fields; Visual Pathways}, Month = {Sep}, Number = {1}, Pages = {187-202}, pmid = {6776164}, Pst = {ppublish}, Title = {Retinotopic organization of striate and extrastriate visual cortex in the mouse}, Volume = {193}, Year = {1980}, url = {papers/Wagor_JCompNeurol1980.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901930113}} @article{Hofbauer:1985, Abstract = {The retinotectal projections in the mouse were analyzed with injections of horseradish peroxidase into the superior colliculus and of radioactive amino acids into the eye. At least 70\% of the ganglion cells, and possibly all of them, were found to project to the superior colliculus, including ganglion cells of all sizes. Small injections revealed that ganglion cells of different sizes terminate at different levels in the superior colliculus. The small ganglion cells that form the vast majority of all cells project predominantly to the upper stratum griseum superficiale. A small population of mainly medium-sized and large ganglion cells project to the deep stratum griseum superficiale and to the stratum opticum. The ipsilateral projection is restricted to the deep stratum griseum superficiale and stratum opticum and consists predominantly of medium-sized and large ganglion cells.}, Author = {Hofbauer, A and Dr{\"a}ger, U C}, Date-Added = {2011-09-08 13:03:10 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {Superior Colliculus; optic tectum; histology; tracer; connectivity; Retina; Retinal Ganglion Cells; Mouse; midbrain; anterograde tracing; retinal wave paper}, Mesh = {Animals; Mice; Mice, Inbred C57BL; Retina; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways}, Month = {Apr}, Number = {4}, Pages = {465-74}, pmid = {3988995}, Pst = {ppublish}, Title = {Depth segregation of retinal ganglion cells projecting to mouse superior colliculus}, Volume = {234}, Year = {1985}, url = {papers/Hofbauer_JCompNeurol1985.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902340405}} @article{Borghuis:2011, Abstract = {Decoding the wiring diagram of the retina requires simultaneous observation of activity in identified neuron populations. Available recording methods are limited in their scope: electrodes can access only a small fraction of neurons at once, whereas synthetic fluorescent indicator dyes label tissue indiscriminately. Here, we describe a method for studying retinal circuitry at cellular and subcellular levels combining two-photon microscopy and a genetically encoded calcium indicator. Using specific viral and promoter constructs to drive expression of GCaMP3, we labeled all five major neuron classes in the adult mouse retina. Stimulus-evoked GCaMP3 responses as imaged by two-photon microscopy permitted functional cell type annotation. Fluorescence responses were similar to those measured with the small molecule dye OGB-1. Fluorescence intensity correlated linearly with spike rates >10 spikes/s, and a significant change in fluorescence always reflected a significant change in spike firing rate. GCaMP3 expression had no apparent effect on neuronal function. Imaging at subcellular resolution showed compartment-specific calcium dynamics in multiple identified cell types.}, Author = {Borghuis, Bart G and Tian, Lin and Xu, Ying and Nikonov, Sergei S and Vardi, Noga and Zemelman, Boris V and Looger, Loren L}, Date-Added = {2011-08-31 11:16:57 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {frontiers review; calcium imaging; optical physiology; calcium sensor; gene; viral; retinal; microscopy; Technique; Genetic Markers}, Mesh = {Action Potentials; Animals; Female; Male; Mice; Mice, Inbred C57BL; Neurons; Organ Culture Techniques; Retina; Vision, Ocular; Voltage-Sensitive Dye Imaging}, Month = {Feb}, Number = {8}, Pages = {2855-67}, pmid = {21414907}, Pst = {ppublish}, Title = {Imaging light responses of targeted neuron populations in the rodent retina}, Volume = {31}, Year = {2011}, url = {papers/Borghuis_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.6064-10.2011}} @article{Yamada:2010, Abstract = {Axonal branching is thought to be regulated not only by genetically defined programs but also by neural activity in the developing nervous system. Here we investigated the role of pre- and postsynaptic activity in axon branching in the thalamocortical (TC) projection using organotypic coculture preparations of the thalamus and cortex. Individual TC axons were labeled with enhanced yellow fluorescent protein by transfection into thalamic neurons. To manipulate firing activity, a vector encoding an inward rectifying potassium channel (Kir2.1) was introduced into either thalamic or cortical cells. Firing activity was monitored with multielectrode dishes during culturing. We found that axon branching was markedly suppressed in Kir2.1-overexpressing thalamic cells, in which neural activity was silenced. Similar suppression of TC axon branching was also found when cortical cell activity was reduced by expressing Kir2.1. These results indicate that both pre- and postsynaptic activity is required for TC axon branching during development.}, Author = {Yamada, Akito and Uesaka, Naofumi and Hayano, Yasufumi and Tabata, Toshihide and Kano, Masanobu and Yamamoto, Nobuhiko}, Date-Added = {2011-08-24 17:02:12 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {activity manipulation; frontiers review; development; structural remodeling; Structure-Activity Relationship; 21 Activity-development}, Mesh = {Action Potentials; Animals; Axons; Coculture Techniques; Gene Silencing; Gene Transfer Techniques; Models, Neurological; Nerve Net; Neural Pathways; Neurons; Plasmids; Potassium Channels, Inwardly Rectifying; Rats; Rats, Sprague-Dawley; Thalamus}, Month = {Apr}, Number = {16}, Pages = {7562-7}, Pmc = {PMC2867758}, pmid = {20368417}, Pst = {ppublish}, Title = {Role of pre- and postsynaptic activity in thalamocortical axon branching}, Volume = {107}, Year = {2010}, url = {papers/Yamada_ProcNatlAcadSciUSA2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0900613107}} @article{Koch:2011, Abstract = {A hallmark of mammalian neural circuit development is the refinement of initially imprecise connections by competitive activity-dependent processes. In the developing visual system retinal ganglion cell (RGC) axons from the two eyes undergo activity-dependent competition for territory in the dorsal lateral geniculate nucleus (dLGN). The direct contributions of synaptic transmission to this process, however, remain unclear. We used a genetic approach to reduce glutamate release selectively from ipsilateral-projecting RGCs and found that their release-deficient axons failed to exclude competing axons from the ipsilateral eye territory in the dLGN. Nevertheless, the release-deficient axons consolidated and maintained their normal amount of dLGN territory, even in the face of fully active competing axons. These results show that during visual circuit refinement glutamatergic transmission plays a direct role in excluding competing axons from inappropriate target regions, but they argue that consolidation and maintenance of axonal territory are largely insensitive to alterations in synaptic activity levels.}, Author = {Koch, Selina M and Dela Cruz, Cassandra G and Hnasko, Thomas S and Edwards, Robert H and Huberman, Andrew D and Ullian, Erik M}, Date-Added = {2011-08-23 09:19:51 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Spontaneous activity; retinal wave paper; retinal projections; Retinal Ganglion Cells; LGN; development; activity manipulation; frontiers review}, Month = {Jul}, Number = {2}, Pages = {235-42}, pmid = {21791283}, Pst = {ppublish}, Title = {Pathway-specific genetic attenuation of glutamate release alters select features of competition-based visual circuit refinement}, Volume = {71}, Year = {2011}, url = {papers/Koch_Neuron2011.pdf}, Bdsk-File-2 = {papers/Koch_Neuron2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.05.045}} @article{Heim:2004, Abstract = {Genetic calcium probes offer tremendous potential in the fields of neuroscience, cell biology, and pharmaceutical screening. Previously, ratiometric and non-ratiometric indicators of cellular calcium dynamics have been described that consist of mutants of the green fluorescent protein (GFP) as fluorophores and calmodulin as calcium-binding moiety in several configurations. However, these calmodulin-based types of probes have a series of deficiencies, such as reduced dynamic ranges, when expressed within transgenic organisms and lack of calcium sensitivity in certain targetings. We developed novel types of calcium probes based on troponin C variants from skeletal and cardiac muscle. These indicators have ratio changes up to 140\%, K(d)s ranging from 470 nm to 29 microm, and improved subcellular targeting properties. We targeted the indicators to the plasma membrane of HEK293 cells and primary hippocampal neurons. Upon long lasting depolarization, submembrane calcium levels in hippocampal neurons were found to be in equilibrium with bulk cytosolic calcium levels, suggesting no standing gradient persists from the membrane toward the cytosol. We expect that such novel indicators using specialized calcium sensing proteins will be minimally interacting with the cellular biochemical machinery.}, Author = {Heim, Nicola and Griesbeck, Oliver}, Date-Added = {2011-08-17 13:27:58 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Biol Chem}, Journal-Full = {The Journal of biological chemistry}, Keywords = {optical imaging; calcium imaging; calcium sensor; gene; Technique; frontiers review}, Mesh = {Animals; Calcium; Cells, Cultured; Chickens; Cloning, Molecular; Fluorescent Dyes; Green Fluorescent Proteins; Hippocampus; Humans; Indicators and Reagents; Kidney; Luminescent Proteins; Microscopy, Fluorescence; Muscle, Skeletal; Myocardium; Neurons; Rats; Transgenes; Troponin C}, Month = {Apr}, Number = {14}, Pages = {14280-6}, pmid = {14742421}, Pst = {ppublish}, Title = {Genetically encoded indicators of cellular calcium dynamics based on troponin C and green fluorescent protein}, Volume = {279}, Year = {2004}, url = {papers/Heim_JBiolChem2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1074/jbc.M312751200}} @article{Muto:2011, Abstract = {Animal behaviors are generated by well-coordinated activation of neural circuits. In zebrafish, embryos start to show spontaneous muscle contractions at 17 to 19 h postfertilization. To visualize how motor circuits in the spinal cord are activated during this behavior, we developed GCaMP-HS (GCaMP-hyper sensitive), an improved version of the genetically encoded calcium indicator GCaMP, and created transgenic zebrafish carrying the GCaMP-HS gene downstream of the Gal4-recognition sequence, UAS (upstream activation sequence). Then we performed a gene-trap screen and identified the SAIGFF213A transgenic fish that expressed Gal4FF, a modified version of Gal4, in a subset of spinal neurons including the caudal primary (CaP) motor neurons. We conducted calcium imaging using the SAIGFF213A; UAS:GCaMP-HS double transgenic embryos during the spontaneous contractions. We demonstrated periodic and synchronized activation of a set of ipsilateral motor neurons located on the right and left trunk in accordance with actual muscle movements. The synchronized activation of contralateral motor neurons occurred alternately with a regular interval. Furthermore, a detailed analysis revealed rostral-to-caudal propagation of activation of the ipsilateral motor neuron, which is similar to but much slower than the rostrocaudal delay observed during swimming in later stages. Our study thus demonstrated coordinated activities of the motor neurons during the first behavior in a vertebrate. We propose the GCaMP technology combined with the Gal4FF-UAS system is a powerful tool to study functional neural circuits in zebrafish.}, Author = {Muto, Akira and Ohkura, Masamichi and Kotani, Tomoya and Higashijima, Shin-ichi and Nakai, Junichi and Kawakami, Koichi}, Date-Added = {2011-08-17 13:24:11 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Zebrafish; Motor Neurons; Spinal Cord; calcium imaging; optical physiology; calcium sensor; gene; Technique}, Mesh = {Animals; Animals, Genetically Modified; Behavior, Animal; Calcium; Green Fluorescent Proteins; Indicators and Reagents; Motor Activity; Motor Neurons; Muscle Contraction; Spinal Cord; Zebrafish}, Month = {Mar}, Number = {13}, Pages = {5425-30}, Pmc = {PMC3069178}, pmid = {21383146}, Pst = {ppublish}, Title = {Genetic visualization with an improved GCaMP calcium indicator reveals spatiotemporal activation of the spinal motor neurons in zebrafish}, Volume = {108}, Year = {2011}, url = {papers/Muto_ProcNatlAcadSciUSA2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1000887108}} @article{Higashijima:2003, Abstract = {Genetically encoded calcium indicators, such as cameleon, have offered the promise of noninvasively monitoring activity of neurons, but no one has demonstrated whether these indicators can report calcium transients in neurons of behaving vertebrates. We show that cameleon can be expressed at high levels in sensory and spinal cord neurons in zebrafish by using neural-specific promoters in both transient expression experiments and in a stable transgenic line. Using standard confocal microscopy, calcium transients in identified motoneurons and spinal interneurons could be detected during escape behaviors produced by a touch on the head of the fish. Small movements of the restrained fish during the behavior did not represent a major problem for analyzing the calcium responses because of the ratiometric nature of cameleon. We conclude that cameleon can be used to noninvasively study the activity of neurons in an intact, behaving vertebrate. The ability to introduce an indicator genetically allows for studies of the functional roles of local interneurons that cannot easily be monitored with other approaches. Transgenic lines such as the one we generated can also be crossed into mutant lines of fish to study both structural and functional consequences of the mutations.}, Author = {Higashijima, Shin-ichi and Masino, Mark A and Mandel, Gail and Fetcho, Joseph R}, Date-Added = {2011-08-17 13:17:05 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {calcium sensor; calcium imaging; optical imaging; optical physiology; 21 Neurophysiology; Zebrafish; gene; frontiers review}, Mesh = {Animals; Animals, Genetically Modified; Behavior, Animal; Calcium Signaling; Calcium-Binding Proteins; DNA, Complementary; Drosophila Proteins; Electric Stimulation; Electrophysiology; Embryo, Nonmammalian; Escape Reaction; Interneurons; Microscopy, Confocal; Motor Neurons; Neurons; Patch-Clamp Techniques; Plasmids; Zebrafish}, Month = {Dec}, Number = {6}, Pages = {3986-97}, pmid = {12930818}, Pst = {ppublish}, Title = {Imaging neuronal activity during zebrafish behavior with a genetically encoded calcium indicator}, Volume = {90}, Year = {2003}, url = {papers/Higashijima_JNeurophysiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00576.2003}} @article{Kerr:2000, Abstract = {Electrophysiology and optical indicators have been used in vertebrate systems to investigate excitable cell firing and calcium transients, but both techniques have been difficult to apply in organisms with powerful reverse genetics. To overcome this limitation, we expressed cameleon proteins, genetically encoded calcium indicators, in the pharyngeal muscle of the nematode worm Caenorhabditis elegans. In intact transgenic animals expressing cameleons, fluorescence ratio changes accompanied muscular contraction, verifying detection of calcium transients. By comparing the magnitude and duration of calcium influx in wild-type and mutant animals, we were able to determine the effects of calcium channel proteins on pharyngeal calcium transients. We also successfully used cameleons to detect electrically evoked calcium transients in individual C. elegans neurons. This technique therefore should have broad applications in analyzing the regulation of excitable cell activity in genetically tractable organisms.}, Author = {Kerr, R and Lev-Ram, V and Baird, G and Vincent, P and Tsien, R Y and Schafer, W R}, Date-Added = {2011-08-17 12:25:17 -0400}, Date-Modified = {2011-08-17 12:26:08 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical imaging; optical physiology; frontiers review; Caenorhabditis elegans; Behavior; sensory map; calcium imaging; calcium sensor; gene}, Mesh = {Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcium; Calcium Channels; Down-Regulation; Electrophysiology; Helminth Proteins; Muscle Proteins; Mutation; Neurons; Optics and Photonics; Pharyngeal Muscles; Protein Isoforms}, Month = {Jun}, Number = {3}, Pages = {583-94}, pmid = {10896155}, Pst = {ppublish}, Title = {Optical imaging of calcium transients in neurons and pharyngeal muscle of C. elegans}, Volume = {26}, Year = {2000}, url = {papers/Kerr_Neuron2000.pdf}} @article{Jayaraman:2007, Abstract = {Genetically encoded optical indicators hold the promise of enabling non-invasive monitoring of activity in identified neurons in behaving organisms. However, the interpretation of images of brain activity produced using such sensors is not straightforward. Several recent studies of sensory coding used G-CaMP 1.3-a calcium sensor-as an indicator of neural activity; some of these studies characterized the imaged neurons as having narrow tuning curves, a conclusion not always supported by parallel electrophysiological studies. To better understand the possible cause of these conflicting results, we performed simultaneous in vivo 2-photon imaging and electrophysiological recording of G-CaMP 1.3 expressing neurons in the antennal lobe (AL) of intact fruitflies. We find that G-CaMP has a relatively high threshold, that its signal often fails to capture spiking response kinetics, and that it can miss even high instantaneous rates of activity if those are not sustained. While G-CaMP can be misleading, it is clearly useful for the identification of promising neural targets: when electrical activity is well above the sensor's detection threshold, its signal is fairly well correlated with mean firing rate and G-CaMP does not appear to alter significantly the responses of neurons that express it. The methods we present should enable any genetically encoded sensor, activator, or silencer to be evaluated in an intact neural circuit in vivo in Drosophila.}, Author = {Jayaraman, Vivek and Laurent, Gilles}, Date-Added = {2011-08-17 12:21:43 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Drosophila; Behavior; microscopy; 21 Neurophysiology; sensory map; Olfactory Bulb; frontiers review}, Pages = {3}, Pmc = {PMC2526281}, pmid = {18946545}, Pst = {ppublish}, Title = {Evaluating a genetically encoded optical sensor of neural activity using electrophysiology in intact adult fruit flies}, Volume = {1}, Year = {2007}, url = {papers/Jayaraman_FrontNeuralCircuits2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.04.003.2007}} @article{Chalasani:2007, Abstract = {Although many properties of the nervous system are shared among animals and systems, it is not known whether different neuronal circuits use common strategies to guide behaviour. Here we characterize information processing by Caenorhabditis elegans olfactory neurons (AWC) and interneurons (AIB and AIY) that control food- and odour-evoked behaviours. Using calcium imaging and mutations that affect specific neuronal connections, we show that AWC neurons are activated by odour removal and activate the AIB interneurons through AMPA-type glutamate receptors. The level of calcium in AIB interneurons is elevated for several minutes after odour removal, a neuronal correlate to the prolonged behavioural response to odour withdrawal. The AWC neuron inhibits AIY interneurons through glutamate-gated chloride channels; odour presentation relieves this inhibition and results in activation of AIY interneurons. The opposite regulation of AIY and AIB interneurons generates a coordinated behavioural response. Information processing by this circuit resembles information flow from vertebrate photoreceptors to 'OFF' bipolar and 'ON' bipolar neurons, indicating a conserved or convergent strategy for sensory information processing.}, Author = {Chalasani, Sreekanth H and Chronis, Nikos and Tsunozaki, Makoto and Gray, Jesse M and Ramot, Daniel and Goodman, Miriam B and Bargmann, Cornelia I}, Date-Added = {2011-08-17 12:14:33 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Caenorhabditis elegans; Behavior; calcium imaging; calcium sensor; optical physiology; optical imaging; frontiers review}, Mesh = {Animals; Caenorhabditis elegans; Calcium; Exploratory Behavior; Glutamic Acid; Interneurons; Movement; Neurons; Odors; Receptors, Glutamate; Smell; Synapses}, Month = {Nov}, Number = {7166}, Pages = {63-70}, pmid = {17972877}, Pst = {ppublish}, Title = {Dissecting a circuit for olfactory behaviour in Caenorhabditis elegans}, Volume = {450}, Year = {2007}, url = {papers/Chalasani_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06292}} @article{Yasuda:2011, Abstract = {Efficient memory formation relies on the establishment of functional hippocampal circuits. It has been proposed that synaptic connections are refined by neural activity to form functional brain circuitry. However, it is not known whether and how hippocampal connections are refined by neural activity in vivo. Using a mouse genetic system in which restricted populations of neurons in the hippocampal circuit are inactivated, we show that inactive axons are eliminated after they develop through a competition with active axons. Remarkably, in the dentate gyrus, which undergoes neurogenesis throughout life, axon refinement is achieved by a competition between mature and young neurons. These results demonstrate that activity-dependent competition plays multiple roles in the establishment of functional memory circuits in vivo.}, Author = {Yasuda, Masahiro and Johnson-Venkatesh, Erin M and Zhang, Helen and Parent, Jack M and Sutton, Michael A and Umemori, Hisashi}, Date-Added = {2011-08-17 10:55:26 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {development; hippocampus; Dentate Gyrus; adult neurogenesis; Technique; activity manipulation; mice; Gene Transfer Techniques; structural remodeling; synapse formation; synapses; plasticity}, Mesh = {Animals; Axons; Cell Aging; Dentate Gyrus; Entorhinal Cortex; Gene Silencing; Hippocampus; Memory; Mice; Mice, Transgenic; Neural Inhibition; Neural Pathways; Neurogenesis; Neuronal Plasticity; Neurons}, Month = {Jun}, Number = {6}, Pages = {1128-42}, Pmc = {PMC3124368}, pmid = {21689599}, Pst = {ppublish}, Title = {Multiple forms of activity-dependent competition refine hippocampal circuits in vivo}, Volume = {70}, Year = {2011}, url = {papers/Yasuda_Neuron2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.04.027}} @article{Johnson:2011, Abstract = {Spontaneous action potential activity is crucial for mammalian sensory system development. In the auditory system, patterned firing activity has been observed in immature spiral ganglion and brain-stem neurons and is likely to depend on cochlear inner hair cell (IHC) action potentials. It remains uncertain whether spiking activity is intrinsic to developing IHCs and whether it shows patterning. We found that action potentials were intrinsically generated by immature IHCs of altricial rodents and that apical IHCs showed bursting activity as opposed to more sustained firing in basal cells. We show that the efferent neurotransmitter acetylcholine fine-tunes the IHC's resting membrane potential (V(m)), and as such is crucial for the bursting pattern in apical cells. Endogenous extracellular ATP also contributes to the V(m) of apical and basal IHCs by triggering small-conductance Ca(2+)-activated K(+) (SK2) channels. We propose that the difference in firing pattern along the cochlea instructs the tonotopic differentiation of IHCs and auditory pathway.}, Author = {Johnson, Stuart L and Eckrich, Tobias and Kuhn, Stephanie and Zampini, Valeria and Franz, Christoph and Ranatunga, Kishani M and Roberts, Terri P and Masetto, Sergio and Knipper, Marlies and Kros, Corn{\'e} J and Marcotti, Walter}, Date-Added = {2011-08-17 10:51:42 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Spontaneous activity; retinal wave paper; rat; rodent; Auditory Pathways; Cochlea/innervation/physiology; Cochlear Nerve; 21 Activity-development; 21 Neurophysiology; Electrophysiology; extracellular}, Month = {Jun}, Number = {6}, Pages = {711-7}, Pmc = {PMC3103712}, pmid = {21572434}, Pst = {ppublish}, Title = {Position-dependent patterning of spontaneous action potentials in immature cochlear inner hair cells}, Volume = {14}, Year = {2011}, url = {papers/Johnson_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2803}} @article{Rochefort:2011, Abstract = {Previous studies of the ferret visual cortex indicate that the development of direction selectivity requires visual experience. Here, we used two-photon calcium imaging to study the development of direction selectivity in layer 2/3 neurons of the mouse visual cortex in vivo. Surprisingly, just after eye opening nearly all orientation-selective neurons were also direction selective. During later development, the number of neurons responding to drifting gratings increased in parallel with the fraction of neurons that were orientation, but not direction, selective. Our experiments demonstrate that direction selectivity develops normally in dark-reared mice, indicating that the early development of direction selectivity is independent of visual experience. Furthermore, remarkable functional similarities exist between the development of direction selectivity in cortical neurons and the previously reported development of direction selectivity in the mouse retina. Together, these findings provide strong evidence that the development of orientation and direction selectivity in the mouse brain is distinctly different from that in ferrets.}, Author = {Rochefort, Nathalie L and Narushima, Madoka and Grienberger, Christine and Marandi, Nima and Hill, Daniel N and Konnerth, Arthur}, Date-Added = {2011-08-16 18:22:53 -0400}, Date-Modified = {2013-05-21 20:36:03 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {development; 21 Activity-development; topographic map; visual system; visual cortex; neocortex; mice; calcium imaging; optical physiology; multiphoton; microscopy; Spontaneous activity; retinal wave paper; currOpinRvw}, Month = {Aug}, Number = {3}, Pages = {425-32}, pmid = {21835340}, Pst = {ppublish}, Title = {Development of direction selectivity in mouse cortical neurons}, Volume = {71}, Year = {2011}, url = {papers/Rochefort_Neuron2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.06.013}} @article{Soteropoulos:2011, Abstract = {Strong experimental evidence implicates the corticospinal tract in voluntary control of the contralateral forelimb. Its potential role in controlling the ipsilateral forelimb is less well understood, although anatomical projections to ipsilateral spinal circuits are identified. We investigated inputs to motoneurons innervating hand and forearm muscles from the ipsilateral corticospinal tract using multiple methods. Intracellular recordings from 62 motoneurons in three anesthetized monkeys revealed no monosynaptic and only one weak oligosynaptic EPSP after stimulation of the ipsilateral corticospinal tract. Single stimulus intracortical microstimulation of the primary motor cortex (M1) in awake animals failed to produce any responses in ipsilateral muscles. Strong stimulation (>500 μA, single stimulus) of the majority of corticospinal axons at the medullary pyramids revealed only weak suppressions in ipsilateral muscles at longer latencies than the robust facilitations seen contralaterally. Spike-triggered averaging of ipsilateral muscle activity from M1 neural discharge (184 cells) did not reveal any postspike effects consistent with monosynaptic corticomotoneuronal connections. We also examined the activity of 191 M1 neurons during ipsilateral or contralateral "reach to precision grip" movements. Many cells (67\%) modulated their activity during ipsilateral limb movement trials (compared with 90\% with contralateral trials), but the timing of this activity was best correlated with weak muscle activity in the contralateral nonmoving arm. We conclude that, in normal adults, any inputs to forelimb motoneurons from the ipsilateral corticospinal tract are weak and indirect and that modulation of M1 cell firing seems to be related primarily to control of the contralateral limb.}, Author = {Soteropoulos, Demetris S and Edgley, Steve A and Baker, Stuart N}, Date-Added = {2011-08-16 18:18:15 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Motor Cortex; function; monkey; Neurophysiology; Spinal Cord; Motor Neurons; connectivity}, Month = {Aug}, Number = {31}, Pages = {11208-19}, pmid = {21813682}, Pst = {ppublish}, Title = {Lack of evidence for direct corticospinal contributions to control of the ipsilateral forelimb in monkey}, Volume = {31}, Year = {2011}, url = {papers/Soteropoulos_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0257-11.2011}} @article{Butts:2011, Abstract = {Visual neurons can respond with extremely precise temporal patterning to visual stimuli that change on much slower time scales. Here, we investigate how the precise timing of cat thalamic spike trains-which can have timing as precise as 1 ms-is related to the stimulus, in the context of both artificial noise and natural visual stimuli. Using a nonlinear modeling framework applied to extracellular data, we demonstrate that the precise timing of thalamic spike trains can be explained by the interplay between an excitatory input and a delayed suppressive input that resembles inhibition, such that neuronal responses only occur in brief windows where excitation exceeds suppression. The resulting description of thalamic computation resembles earlier models of contrast adaptation, suggesting a more general role for mechanisms of contrast adaptation in visual processing. Thus, we describe a more complex computation underlying thalamic responses to artificial and natural stimuli that has implications for understanding how visual information is represented in the early stages of visual processing.}, Author = {Butts, Daniel A and Weng, Chong and Jin, Jianzhong and Alonso, Jose-Manuel and Paninski, Liam}, Date-Added = {2011-08-16 18:15:45 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {visual system; function; topographic map; LGN; cat; Theoretical; 21 Neurophysiology}, Month = {Aug}, Number = {31}, Pages = {11313-27}, pmid = {21813691}, Pst = {ppublish}, Title = {Temporal Precision in the Visual Pathway through the Interplay of Excitation and Stimulus-Driven Suppression}, Volume = {31}, Year = {2011}, url = {papers/Butts_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0434-11.2011}} @article{Paige:2011, Abstract = {Green fluorescent protein (GFP) and its derivatives have transformed the use and analysis of proteins for diverse applications. Like proteins, RNA has complex roles in cellular function and is increasingly used for various applications, but a comparable approach for fluorescently tagging RNA is lacking. Here, we describe the generation of RNA aptamers that bind fluorophores resembling the fluorophore in GFP. These RNA-fluorophore complexes create a palette that spans the visible spectrum. An RNA-fluorophore complex, termed Spinach, resembles enhanced GFP and emits a green fluorescence comparable in brightness with fluorescent proteins. Spinach is markedly resistant to photobleaching, and Spinach fusion RNAs can be imaged in living cells. These RNA mimics of GFP provide an approach for genetic encoding of fluorescent RNAs.}, Author = {Paige, Jeremy S and Wu, Karen Y and Jaffrey, Samie R}, Date-Added = {2011-08-16 18:13:56 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Technique; Reporter/genetics; RNA; Fluorescent Dyes}, Mesh = {Aptamers, Nucleotide; Benzyl Compounds; Biomimetics; Cell Nucleus; Cytoplasmic Granules; Cytosol; Fluorescence; Green Fluorescent Proteins; HEK293 Cells; Humans; Imidazolines; Molecular Mimicry; Nucleic Acid Conformation; Photobleaching; Protein Binding; RNA, Untranslated; SELEX Aptamer Technique; Spectrometry, Fluorescence; Sucrose}, Month = {Jul}, Number = {6042}, Pages = {642-6}, pmid = {21798953}, Pst = {ppublish}, Title = {RNA mimics of green fluorescent protein}, Volume = {333}, Year = {2011}, url = {papers/Paige_Science2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1207339}} @article{Kralj:2011, Abstract = {Bacteria have many voltage- and ligand-gated ion channels, and population-level measurements indicate that membrane potential is important for bacterial survival. However, it has not been possible to probe voltage dynamics in an intact bacterium. Here we developed a method to reveal electrical spiking in Escherichia coli. To probe bacterial membrane potential, we engineered a voltage-sensitive fluorescent protein based on green-absorbing proteorhodopsin. Expression of the proteorhodopsin optical proton sensor (PROPS) in E. coli revealed electrical spiking at up to 1 hertz. Spiking was sensitive to chemical and physical perturbations and coincided with rapid efflux of a small-molecule fluorophore, suggesting that bacterial efflux machinery may be electrically regulated.}, Author = {Kralj, Joel M and Hochbaum, Daniel R and Douglass, Adam D and Cohen, Adam E}, Date-Added = {2011-08-16 17:39:27 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {optical physiology; Bacteria; Neurophysiology}, Mesh = {Action Potentials; Escherichia coli; Fluorescence; Fluorescent Dyes; Hydrogen-Ion Concentration; Ion Channels; Ion Transport; Light; Membrane Potentials; Protons; Rhodamines; Rhodopsin; Spectrometry, Fluorescence; Stress, Physiological}, Month = {Jul}, Number = {6040}, Pages = {345-8}, pmid = {21764748}, Pst = {ppublish}, Title = {Electrical spiking in Escherichia coli probed with a fluorescent voltage-indicating protein}, Volume = {333}, Year = {2011}, url = {papers/Kralj_Science2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1204763}} @article{Ray:2011, Abstract = {Physiological homeostasis is essential for organism survival. Highly responsive neuronal networks are involved, but their constituent neurons are just beginning to be resolved. To query brain serotonergic neurons in homeostasis, we used a neuronal silencing tool, mouse RC::FPDi (based on the synthetic G protein-coupled receptor Di), designed for cell type-specific, ligand-inducible, and reversible suppression of action potential firing. In mice harboring Di-expressing serotonergic neurons, administration of the ligand clozapine-N-oxide (CNO) by systemic injection attenuated the chemoreflex that normally increases respiration in response to tissue carbon dioxide (CO(2)) elevation and acidosis. At the cellular level, CNO suppressed firing rate increases evoked by CO(2) acidosis. Body thermoregulation at room temperature was also disrupted after CNO triggering of Di; core temperatures plummeted, then recovered. This work establishes that serotonergic neurons regulate life-sustaining respiratory and thermoregulatory networks, and demonstrates a noninvasive tool for mapping neuron function.}, Author = {Ray, Russell S and Corcoran, Andrea E and Brust, Rachael D and Kim, Jun Chul and Richerson, George B and Nattie, Eugene and Dymecki, Susan M}, Date-Added = {2011-08-16 17:37:35 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Serotonin; mice; Homeostasis; Acids; respiration; Temperature; Technique; activity manipulation; frontiers review}, Mesh = {Acidosis; Action Potentials; Animals; Body Temperature Regulation; Brain Stem; Carbon Dioxide; Chemoreceptor Cells; Clozapine; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Homeostasis; Hydrogen-Ion Concentration; Ligands; Mice; Mice, Transgenic; Models, Neurological; Neural Inhibition; Neurons; Receptors, G-Protein-Coupled; Respiration; Serotonin}, Month = {Jul}, Number = {6042}, Pages = {637-42}, pmid = {21798952}, Pst = {ppublish}, Title = {Impaired respiratory and body temperature control upon acute serotonergic neuron inhibition}, Volume = {333}, Year = {2011}, url = {papers/Ray_Science2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1205295}} @article{Pangratz-Fuehrer:2011, Abstract = {Parvalbumin-expressing fast-spiking (FS) cells are interconnected via GABAergic and electrical synapses and represent a major class of inhibitory interneurons in the neocortex. Synaptic connections among FS cells are critical for regulating network oscillations in the mature neocortex. However, it is unclear whether synaptic connections among FS interneurons also play a central role in the generation of patterned neuronal activity in the immature brain, which is thought to underlie the formation of neocortical circuits. Here, we investigated the developmental time course of synaptogenesis of FS cell in mouse visual cortex. In layer 5/6 (L5/6), we recorded from two or three FS and/or pyramidal (PYR) neurons to study the development of electrical and chemical synaptic interactions from postnatal day 3 (P3) to P18. We detected no evidence for functional connectivity for FS-FS or FS-PYR pairs at P3-P4. However, by P5-P6, we found that 20\% of FS pairs were electrically coupled, and 24\% of pairs were connected via GABAergic synapses; by P15-P18, 42\% of FS pairs had established functional electrical synapses, and 47\% of FS pairs were connected via GABAergic synapses. FS cell GABAergic inhibition of pyramidal cells showed a similar developmental time line, but no electrical coupling was detected for FS-PYR pairs. We found that synaptogenesis of electrical and GABAergic connections of FS cells takes place in the same period. Together, our results suggest that chemical and electrical connections among FS cells can contribute to patterned neocortical activity only by the end of the first postnatal week.}, Author = {Pangratz-Fuehrer, Susanne and Hestrin, Shaul}, Date-Added = {2011-08-16 17:35:38 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; interneurons; Gap Junctions; 21 Neurophysiology; GABA; Pyramidal Cells; Patch-Clamp Techniques/*methods}, Month = {Jul}, Number = {30}, Pages = {10767-75}, pmid = {21795529}, Pst = {ppublish}, Title = {Synaptogenesis of electrical and GABAergic synapses of fast-spiking inhibitory neurons in the neocortex}, Volume = {31}, Year = {2011}, url = {papers/Pangratz-Fuehrer_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.6655-10.2011}} @article{Yizhar:2011, Abstract = {Severe behavioural deficits in psychiatric diseases such as autism and schizophrenia have been hypothesized to arise from elevations in the cellular balance of excitation and inhibition (E/I balance) within neural microcircuitry. This hypothesis could unify diverse streams of pathophysiological and genetic evidence, but has not been susceptible to direct testing. Here we design and use several novel optogenetic tools to causally investigate the cellular E/I balance hypothesis in freely moving mammals, and explore the associated circuit physiology. Elevation, but not reduction, of cellular E/I balance within the mouse medial prefrontal cortex was found to elicit a profound impairment in cellular information processing, associated with specific behavioural impairments and increased high-frequency power in the 30-80 Hz range, which have both been observed in clinical conditions in humans. Consistent with the E/I balance hypothesis, compensatory elevation of inhibitory cell excitability partially rescued social deficits caused by E/I balance elevation. These results provide support for the elevated cellular E/I balance hypothesis of severe neuropsychiatric disease-related symptoms.}, Author = {Yizhar, Ofer and Fenno, Lief E and Prigge, Matthias and Schneider, Franziska and Davidson, Thomas J and O'Shea, Daniel J and Sohal, Vikaas S and Goshen, Inbal and Finkelstein, Joel and Paz, Jeanne T and Stehfest, Katja and Fudim, Roman and Ramakrishnan, Charu and Huguenard, John R and Hegemann, Peter and Deisseroth, Karl}, Date-Added = {2011-08-16 17:33:44 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optogenetics; mice; in vivo; inhibition; GABA; interneurons; neurological disorder; Behavior; Systems Biology; Neocortex; optical physiology}, Month = {Jul}, pmid = {21796121}, Pst = {aheadofprint}, Title = {Neocortical excitation/inhibition balance in information processing and social dysfunction}, Year = {2011}, url = {papers/Yizhar_Nature2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature10360}} @article{Kremer:2011, Abstract = {In the neocortex, neuronal selectivities for multiple sensorimotor modalities are often distributed in topographical maps thought to emerge during a restricted period in early postnatal development. Rodent barrel cortex contains a somatotopic map for vibrissa identity, but the existence of maps representing other tactile features has not been clearly demonstrated. We addressed the issue of the existence in the rat cortex of an intrabarrel map for vibrissa movement direction using in vivo two-photon imaging. We discovered that the emergence of a direction map in rat barrel cortex occurs long after all known critical periods in the somatosensory system. This map is remarkably specific, taking a pinwheel-like form centered near the barrel center and aligned to the barrel cortex somatotopy. We suggest that this map may arise from intracortical mechanisms and demonstrate by simulation that the combination of spike-timing-dependent plasticity at synapses between layer 4 and layer 2/3 and realistic pad stimulation is sufficient to produce such a map. Its late emergence long after other classical maps suggests that experience-dependent map formation and refinement continue throughout adult life.}, Author = {Kremer, Yves and L{\'e}ger, Jean-Fran{\c c}ois and Goodman, Dan and Brette, Romain and Bourdieu, Laurent}, Date-Added = {2011-08-16 17:31:53 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; development; Somatosensory Cortex; rat; multiphoton; microscopy; in vivo; structural remodeling; topographic map}, Month = {Jul}, Number = {29}, Pages = {10689-700}, pmid = {21775612}, Pst = {ppublish}, Title = {Late emergence of the vibrissa direction selectivity map in the rat barrel cortex}, Volume = {31}, Year = {2011}, url = {papers/Kremer_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.6541-10.2011}} @article{Crisp:2011, Abstract = {Many parts of the nervous system become active before development is complete, including the embryonic spinal cord. Remarkably, although the subject has been debated for over a century (Harrison, 1904), it is still unclear whether such activity is required for normal development of motor circuitry. In Drosophila, embryonic motor output is initially poorly organized, and coordinated crawling-like behavior gradually emerges over the subsequent phase of development. We show that reversibly blocking synaptic transmission during this phase severely delays the first appearance of coordinated movements. When we interfere with the pattern of neuronal firing during this period, coordination is also delayed or blocked. We conclude that there is a period during which endogenous patterns of neuronal activity are required for the normal development of motor circuits in Drosophila.}, Author = {Crisp, Sarah J and Evers, Jan Felix and Bate, Michael}, Date-Added = {2011-08-16 17:30:31 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development; structural remodeling; Spontaneous activity; network; Motor Activity; Motor Neurons; Spinal Cord; Drosophila; retinal wave paper}, Month = {Jul}, Number = {29}, Pages = {10445-50}, pmid = {21775590}, Pst = {ppublish}, Title = {Endogenous patterns of activity are required for the maturation of a motor network}, Volume = {31}, Year = {2011}, url = {papers/Crisp_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0346-11.2011}} @article{Chen:2011, Abstract = {Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and regulate a wide array of light-dependent physiological processes. Genetic ablation of ipRGCs eliminates circadian photoentrainment and severely disrupts the pupillary light reflex (PLR). Here we show that ipRGCs consist of distinct subpopulations that differentially express the Brn3b transcription factor, and can be functionally distinguished. Brn3b-negative M1 ipRGCs innervate the suprachiasmatic nucleus (SCN) of the hypothalamus, whereas Brn3b-positive ipRGCs innervate all other known brain targets, including the olivary pretectal nucleus. Consistent with these innervation patterns, selective ablation of Brn3b-positive ipRGCs severely disrupts the PLR, but does not impair circadian photoentrainment. Thus, we find that molecularly distinct subpopulations of M1 ipRGCs, which are morphologically and electrophysiologically similar, innervate different brain regions to execute specific light-induced functions.}, Author = {Chen, S-K and Badea, T C and Hattar, S}, Date-Added = {2011-08-16 17:29:15 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {retina; Retinal Ganglion Cells; entrainment; melanopsin; visual system; mice}, Month = {Aug}, Number = {7358}, Pages = {92-5}, Pmc = {PMC3150726}, pmid = {21765429}, Pst = {epublish}, Title = {Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs}, Volume = {476}, Year = {2011}, url = {papers/Chen_Nature2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature10206}} @article{Croen:2011, Abstract = {CONTEXT: The prevalence of autism spectrum disorders (ASDs) has increased over recent years. Use of antidepressant medications during pregnancy also shows a secular increase in recent decades, prompting concerns that prenatal exposure may contribute to increased risk of ASD. OBJECTIVE: To systematically evaluate whether prenatal exposure to antidepressant medications is associated with increased risk of ASD. DESIGN: Population-based case-control study. Medical records were used to ascertain case children and control children and to derive prospectively recorded information on mothers' use of antidepressant medications, mental health history of mothers, and demographic and medical covariates. SETTING: The Kaiser Permanente Medical Care Program in Northern California. PARTICIPANTS: A total of 298 case children with ASD (and their mothers) and 1507 randomly selected control children (and their mothers) drawn from the membership of the Kaiser Permanente Medical Care Program in Northern California. MAIN OUTCOME MEASURES: ASDs. RESULTS: Prenatal exposure to antidepressant medications was reported for 20 case children (6.7\%) and 50 control children (3.3\%). In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2 [95\% confidence interval, 1.2-4.3]), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8 [95\% confidence interval, 1.8-7.8]). No increase in risk was found for mothers with a history of mental health treatment in the absence of prenatal exposure to selective serotonin reuptake inhibitors. CONCLUSION: Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. The potential risk associated with exposure must be balanced with the risk to the mother or fetus of untreated mental health disorders. Further studies are needed to replicate and extend these findings.}, Author = {Croen, Lisa A and Grether, Judith K and Yoshida, Cathleen K and Odouli, Roxana and Hendrick, Victoria}, Date-Added = {2011-08-16 17:28:25 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Arch Gen Psychiatry}, Journal-Full = {Archives of general psychiatry}, Keywords = {Autistic Disorder; neurological disorder; human; Genetic; Environment}, Month = {Jul}, pmid = {21727247}, Pst = {aheadofprint}, Title = {Antidepressant Use During Pregnancy and Childhood Autism Spectrum Disorders}, Year = {2011}, url = {papers/Croen_ArchGenPsychiatry2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1001/archgenpsychiatry.2011.73}} @article{Hallmayer:2011, Abstract = {CONTEXT: Autism is considered the most heritable of neurodevelopmental disorders, mainly because of the large difference in concordance rates between monozygotic and dizygotic twins. OBJECTIVE: To provide rigorous quantitative estimates of genetic heritability of autism and the effects of shared environment. Design, Setting, and PARTICIPANTS: Twin pairs with at least 1 twin with an autism spectrum disorder (ASD) born between 1987 and 2004 were identified through the California Department of Developmental Services. MAIN OUTCOME MEASURES: Structured diagnostic assessments (Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Schedule) were completed on 192 twin pairs. Concordance rates were calculated and parametric models were fitted for 2 definitions, 1 narrow (strict autism) and 1 broad (ASD). RESULTS: For strict autism, probandwise concordance for male twins was 0.58 for 40 monozygotic pairs (95\% confidence interval [CI], 0.42-0.74) and 0.21 for 31 dizygotic pairs (95\% CI, 0.09-0.43); for female twins, the concordance was 0.60 for 7 monozygotic pairs (95\% CI, 0.28-0.90) and 0.27 for 10 dizygotic pairs (95\% CI, 0.09-0.69). For ASD, the probandwise concordance for male twins was 0.77 for 45 monozygotic pairs (95\% CI, 0.65-0.86) and 0.31 for 45 dizygotic pairs (95\% CI, 0.16-0.46); for female twins, the concordance was 0.50 for 9 monozygotic pairs (95\% CI, 0.16-0.84) and 0.36 for 13 dizygotic pairs (95\% CI, 0.11-0.60). A large proportion of the variance in liability can be explained by shared environmental factors (55\%; 95\% CI, 9\%-81\% for autism and 58\%; 95\% CI, 30\%-80\% for ASD) in addition to moderate genetic heritability (37\%; 95\% CI, 8\%-84\% for autism and 38\%; 95\% CI, 14\%-67\% for ASD). CONCLUSION: Susceptibility to ASD has moderate genetic heritability and a substantial shared twin environmental component.}, Author = {Hallmayer, Joachim and Cleveland, Sue and Torres, Andrea and Phillips, Jennifer and Cohen, Brianne and Torigoe, Tiffany and Miller, Janet and Fedele, Angie and Collins, Jack and Smith, Karen and Lotspeich, Linda and Croen, Lisa A and Ozonoff, Sally and Lajonchere, Clara and Grether, Judith K and Risch, Neil}, Date-Added = {2011-08-16 17:27:01 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Arch Gen Psychiatry}, Journal-Full = {Archives of general psychiatry}, Keywords = {Autistic Disorder; neurological disorder; human; twin study; Genetic; Environment}, Month = {Jul}, pmid = {21727249}, Pst = {aheadofprint}, Title = {Genetic Heritability and Shared Environmental Factors Among Twin Pairs With Autism}, Year = {2011}, url = {papers/Hallmayer_ArchGenPsychiatry2011.pdf}, Bdsk-File-2 = {papers/Hallmayer_ArchGenPsychiatry2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1001/archgenpsychiatry.2011.76}} @article{Johnson:2010, Abstract = {Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) form a light-sensitive system separate from rods and cones. Direct light stimulation of ipRGCs can regulate many nonimage-forming visual functions such as photoentrainment of circadian rhythms and pupil responses, and can intensify migraine headache in adults. In mice, ipRGCs are light responsive as early as the day of birth. In contrast, their eyelids do not open until 12-13 d after birth (P12-13), and light signaling from rods and cones does not begin until approximately P10. No physiological or behavioral function is established for ipRGCs in neonates before the onset of rod and cone signaling. Here we report that mouse pups as young as P6 will completely turn away from a light. Light-induced responses of ipRGCs could be readily recorded in retinas of pups younger than P9, and we found no evidence for rod- and cone-mediated visual signaling to the RGCs of these younger mice. These results confirm that negative phototaxis is evident before the onset of rod- and cone-mediated visual signaling, and well before the onset of image-forming vision. Negative phototaxis was absent in mice lacking melanopsin. We conclude that light activation of melanopsin ipRGCs is necessary and sufficient for negative phototaxis. These results strongly suggest that light activation of ipRGCs may regulate physiological functions such as sleep/wake cycles in preterm and neonatal infants.}, Author = {Johnson, Juliette and Wu, Vincent and Donovan, Michael and Majumdar, Sriparna and Renter{\'\i}a, Ren{\'e} C and Porco, Travis and Van Gelder, Russell N and Copenhagen, David R}, Date-Added = {2011-08-16 17:25:57 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {melanopsin; retina; development; Retinal Ganglion Cells; mice; Behavior}, Mesh = {Animals; Animals, Newborn; Avoidance Learning; Behavior, Animal; Humans; Infant, Newborn; Light; Light Signal Transduction; Mice; Mice, Knockout; Photic Stimulation; Retinal Ganglion Cells; Rod Opsins}, Month = {Oct}, Number = {40}, Pages = {17374-8}, Pmc = {PMC2951438}, pmid = {20855606}, Pst = {ppublish}, Title = {Melanopsin-dependent light avoidance in neonatal mice}, Volume = {107}, Year = {2010}, url = {papers/Johnson_ProcNatlAcadSciUSA2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1008533107}} @article{Paik:2011, Abstract = {The orientation map is a hallmark of primary visual cortex in higher mammals. It is not yet known how orientation maps develop, what function they have in visual processing and why some species lack them. Here we advance the notion that quasi-periodic orientation maps are established by moir{\'e} interference of regularly spaced ON- and OFF-center retinal ganglion cell mosaics. A key prediction of the theory is that the centers of iso-orientation domains must be arranged in a hexagonal lattice on the cortical surface. Here we show that such a pattern is observed in individuals of four different species: monkeys, cats, tree shrews and ferrets. The proposed mechanism explains how orientation maps can develop without requiring precise patterns of spontaneous activity or molecular guidance. Further, it offers a possible account for the emergence of orientation tuning in single neurons despite the absence of orderly orientation maps in rodents species.}, Author = {Paik, Se-Bum and Ringach, Dario L}, Date-Added = {2011-08-16 17:24:17 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {development; retina; visual system; visual cortex; topographic map; Theoretical; Orientation; Spontaneous activity}, Month = {Jul}, Number = {7}, Pages = {919-25}, pmid = {21623365}, Pst = {epublish}, Title = {Retinal origin of orientation maps in visual cortex}, Volume = {14}, Year = {2011}, url = {papers/Paik_NatNeurosci2011.pdf}, Bdsk-File-2 = {papers/Paik_NatNeurosci2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2824}} @article{Wang:2011, Abstract = {A hallmark of mammalian brain evolution is cortical expansion, which reflects an increase in the number of cortical neurons established by the progenitor cell subtypes present and the number of their neurogenic divisions. Recent studies have revealed a new class of radial glia-like (oRG) progenitor cells in the human brain, which reside in the outer subventricular zone. Expansion of the subventricular zone and appearance of oRG cells may have been essential evolutionary steps leading from lissencephalic to gyrencephalic neocortex. Here we show that oRG-like progenitor cells are present in the mouse embryonic neocortex. They arise from asymmetric divisions of radial glia and undergo self-renewing asymmetric divisions to generate neurons. Moreover, mouse oRG cells undergo mitotic somal translocation whereby centrosome movement into the basal process during interphase precedes nuclear translocation. Our finding of oRG cells in the developing rodent brain fills a gap in our understanding of neocortical expansion.}, Author = {Wang, Xiaoqun and Tsai, Jin-Wu and LaMonica, Bridget and Kriegstein, Arnold R}, Date-Added = {2011-08-16 17:22:44 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {development; Neocortex; Stem Cells; radial glia; Embryo}, Mesh = {Age Factors; Animals; Cell Differentiation; Cell Division; Cell Movement; Centrosome; Embryo, Mammalian; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Luminescent Proteins; Mice; Mice, Transgenic; Microscopy, Confocal; Neocortex; Nerve Tissue Proteins; Neuroglia; Neurons; Organ Culture Techniques; Stem Cells; Time Factors}, Month = {May}, Number = {5}, Pages = {555-61}, Pmc = {PMC3083489}, pmid = {21478886}, Pst = {ppublish}, Title = {A new subtype of progenitor cell in the mouse embryonic neocortex}, Volume = {14}, Year = {2011}, url = {papers/Wang_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2807}} @article{Xu:2011, Abstract = {Complex neural circuits in the mammalian brain develop through a combination of genetic instruction and activity-dependent refinement. The relative role of these factors and the form of neuronal activity responsible for circuit development is a matter of significant debate. In the mammalian visual system, retinal ganglion cell projections to the brain are mapped with respect to retinotopic location and eye of origin. We manipulated the pattern of spontaneous retinal waves present during development without changing overall activity levels through the transgenic expression of β2-nicotinic acetylcholine receptors in retinal ganglion cells of mice. We used this manipulation to demonstrate that spontaneous retinal activity is not just permissive, but instructive in the emergence of eye-specific segregation and retinotopic refinement in the mouse visual system. This suggests that specific patterns of spontaneous activity throughout the developing brain are essential in the emergence of specific and distinct patterns of neuronal connectivity.}, Author = {Xu, Hong-ping and Furman, Moran and Mineur, Yann S and Chen, Hui and King, Sarah L and Zenisek, David and Zhou, Z Jimmy and Butts, Daniel A and Tian, Ning and Picciotto, Marina R and Crair, Michael C}, Date-Added = {2011-08-16 17:20:05 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {development; 21 Activity-development; 21 Neurophysiology; Spontaneous activity; retina; retinal wave paper; Superior Colliculus; visual system; structural remodeling; topographic map; currOpinRvw}, Month = {Jun}, Number = {6}, Pages = {1115-27}, Pmc = {PMC3119851}, pmid = {21689598}, Pst = {ppublish}, Title = {An instructive role for patterned spontaneous retinal activity in mouse visual map development}, Volume = {70}, Year = {2011}, url = {papers/Xu_Neuron2011.pdf}, Bdsk-File-2 = {papers/Xu_Neuron2011a.pdf}, Bdsk-File-3 = {papers/Xu_Neuron2011.mpg}, Bdsk-File-4 = {papers/Xu_Neuron2011a.mpg}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.04.028}} @article{Reeves:2011, Abstract = {Calcium signaling has been studied in astrocyte cell bodies using bulk loading of calcium indicator dyes, and astrocytes are known to display intracellular calcium transients. An assumption in recent data on the neuronal impact of somatic astrocyte calcium transients has been that bulk loading reflects signaling in relevant astrocyte compartments such as processes. We assessed bulk loading using Sholl analysis (Sholl, 1953) of astrocytes loaded with common calcium indicator dyes and compared these data with Sholl analysis of astrocyte morphology. In the CA1 region of the hippocampus from rats, we found that bulk loading of calcium indicator dyes only reports on calcium signals within the soma and in the most proximal processes, leaving ∼90\% of the area of an astrocyte and its extensive processes unsampled. By using morphological reconstructions as "maps" after the imaging session, we present simple procedures that remedy these shortfalls and permit reliable detection of calcium transients in distal astrocyte processes. The data thus reveal limitations in the interpretation of astrocyte calcium imaging data gathered with bulk loading and provide refinements to minimize these shortcomings.}, Author = {Reeves, Alexander M B and Shigetomi, Eiji and Khakh, Baljit S}, Date-Added = {2011-08-16 17:19:09 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {calcium imaging; hippocampus; rats; Technique; glia; GFAP; Astrocytes}, Month = {Jun}, Number = {25}, Pages = {9353-8}, Pmc = {PMC3142876}, pmid = {21697385}, Pst = {ppublish}, Title = {Bulk loading of calcium indicator dyes to study astrocyte physiology: key limitations and improvements using morphological maps}, Volume = {31}, Year = {2011}, url = {papers/Reeves_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0127-11.2011}} @article{Bi:2011, Abstract = {Glial fibrillary acidic protein-positive (GFAP(+)) cells give rise to new neurons in the neurogenic niches; whether they are able to generate neurons in the cortical parenchyma is not known. Here, we use genetic fate mapping to examine the progeny of GFAP(+) cells after postnatal hypoxia, a model for the brain injury observed in premature children. After hypoxia, immature cortical astroglia underwent a shift toward neuronal fate and generated cortical excitatory neurons that appeared synaptically integrated into the circuitry. Fate-mapped cortical GFAP(+) cells derived ex vivo from hypoxic, but not normoxic, mice were able to form pluripotent, long-term self-renewing neurospheres. Similarly, exposure to low oxygen conditions in vitro induced stem-cell-like potential in immature cortical GFAP(+) cells. Our data support the conclusion that hypoxia promotes pluripotency in GFAP(+) cells in the cortical parenchyma. Such plasticity possibly explains the cognitive recovery found in some preterm children.}, Author = {Bi, Baoyuan and Salmaso, Natalina and Komitova, Mila and Simonini, Maria V and Silbereis, John and Cheng, Elise and Kim, Janice and Luft, Suzannah and Ment, Laura R and Horvath, Tamas L and Schwartz, Michael L and Vaccarino, Flora M}, Date-Added = {2011-08-16 17:17:18 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Adult Neurogenesis; Neocortex; GFAP; Astrocytes; Hypoxia-Ischemia; development; repair; Stem Cells}, Month = {Jun}, Number = {25}, Pages = {9205-21}, Pmc = {PMC3142780}, pmid = {21697371}, Pst = {ppublish}, Title = {Cortical glial fibrillary acidic protein-positive cells generate neurons after perinatal hypoxic injury}, Volume = {31}, Year = {2011}, url = {papers/Bi_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0518-11.2011}} @article{Feng:2011, Abstract = {Neurons can access signaling molecules through two principal pathways: synaptic transmission ("wiring transmission") and nonsynaptic transmission ("volume transmission"). Wiring transmission is usually considered the far more important mode of neuronal signaling. Using embryonic chick locus ceruleus (LoC) as a model, we quantified and compared routes of delivery of the neurotrophin nerve growth factor (NGF), either through a multisynaptic axonal pathway or via the CSF. We now show that the axonal pathway from the eye to the LoC involves axo-axonic transfer of NGF with receptor switching (p75 to trkA) in the optic tectum. In addition to the axonal pathway, the LoC of chick embryos has privileged access to the CSF through a specialized glial/ependymal cell type, the tanycyte. The avian LoC internalizes from the CSF in a highly specific fashion both NGF and the hormone urotensin (corticotropin-releasing factor family ligand). Quantitative autoradiography at the ultrastructural level shows that tanycytes transcytose and deliver NGF to LoC neurons via synaptoid contacts. The LoC-associated tanycytes express both p75 and trkA receptors. The NGF extracted by tanycytes from the CSF has physiological effects on LoC neurons, as evidenced by significantly altered nuclear diameters in both gain-of-function and loss-of-function experiments. Quantification of NGF extraction shows that, compared with multisynaptic axonal routes of NGF trafficking to LoC, the tanycyte route is significantly more effective. We conclude that some clinically important neuronal populations such as the LoC can use a highly efficient "back door" interface to the CSF and can receive signals via this tanycyte-controlled pathway.}, Author = {Feng, Cheng-Yuan and Wiggins, Larisa M and von Bartheld, Christopher S}, Date-Added = {2011-08-16 16:55:46 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Month = {Jun}, Number = {25}, Pages = {9147-58}, pmid = {21697366}, Pst = {ppublish}, Title = {The locus ceruleus responds to signaling molecules obtained from the CSF by transfer through tanycytes}, Volume = {31}, Year = {2011}, url = {papers/Feng_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5018-10.2011}} @article{Kohler:2011, Abstract = {We studied two groups of adult macaque monkeys to determine the time course of adult neurogenesis in the dentate gyrus of the hippocampus. In the first group, six adult monkeys (Macaca mulatta) received a single injection of the thymidine analog BrdU (75 mg/kg), which is incorporated into replicating DNA and serves as a marker for new cell birth. Brain tissue was collected 48 h, 2 wk, and 6 wk after BrdU injection to examine the initial stages of neurogenesis. Because mature neurons were not evident at 6 wk, we examined tissue collected over a longer time course in a second study. In this study, eight monkeys (Macaca fascicularis) who were subjects in a separate exercise study received 10 weekly injections of BrdU (75 mg/kg), and brain tissue was collected at 16 and 28 wk from the first injection. Based on the timing of expression of neuronal cell markers (βIII-tubulin, doublecortin, NeuN), the extent of dendritic arborization, and acquisition of mature cell body morphology, we show that granule cell maturation in the dentate gyrus of a nonhuman primate is protracted over a minimum of a 6-mo time period, more than 6 times longer than in rodents. The lengthened time course for new cell maturation in nonhuman primates may be appropriate for preservation of neural plasticity over their longer life span and is relevant to our understanding of antidepressant and other therapies that have been linked to neurogenesis in humans.}, Author = {Kohler, Shawn J and Williams, Nancy I and Stanton, Gregory B and Cameron, Judy L and Greenough, William T}, Date-Added = {2011-08-16 16:54:03 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Adult Neurogenesis; hippocampus; Primates; brdu; Dentate Gyrus; monkey}, Month = {Jun}, Number = {25}, Pages = {10326-31}, Pmc = {PMC3121825}, pmid = {21646517}, Pst = {ppublish}, Title = {Maturation time of new granule cells in the dentate gyrus of adult macaque monkeys exceeds six months}, Volume = {108}, Year = {2011}, url = {papers/Kohler_ProcNatlAcadSciUSA2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1017099108}} @article{Schyns:2011, Abstract = {Neural oscillations are ubiquitous measurements of cognitive processes and dynamic routing and gating of information. The fundamental and so far unresolved problem for neuroscience remains to understand how oscillatory activity in the brain codes information for human cognition. In a biologically relevant cognitive task, we instructed six human observers to categorize facial expressions of emotion while we measured the observers' EEG. We combined state-of-the-art stimulus control with statistical information theory analysis to quantify how the three parameters of oscillations (i.e., power, phase, and frequency) code the visual information relevant for behavior in a cognitive task. We make three points: First, we demonstrate that phase codes considerably more information (2.4 times) relating to the cognitive task than power. Second, we show that the conjunction of power and phase coding reflects detailed visual features relevant for behavioral response--that is, features of facial expressions predicted by behavior. Third, we demonstrate, in analogy to communication technology, that oscillatory frequencies in the brain multiplex the coding of visual features, increasing coding capacity. Together, our findings about the fundamental coding properties of neural oscillations will redirect the research agenda in neuroscience by establishing the differential role of frequency, phase, and amplitude in coding behaviorally relevant information in the brain.}, Author = {Schyns, Philippe G and Thut, Gregor and Gross, Joachim}, Date-Added = {2011-08-16 16:50:18 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {Add Keywords}, Month = {May}, Number = {5}, Pages = {e1001064}, Pmc = {PMC3096604}, pmid = {21610856}, Pst = {ppublish}, Title = {Cracking the code of oscillatory activity}, Volume = {9}, Year = {2011}, url = {papers/Schyns_PLoSBiol2011.pdf}, Bdsk-File-2 = {papers/Schyns_PLoSBiol2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1001064}} @article{De-Marco-Garcia:2011, Abstract = {Electrical activity has been shown to regulate development in a variety of species and in various structures, including the retina, spinal cord and cortex. Within the mammalian cortex specifically, the development of dendrites and commissural axons in pyramidal cells is activity-dependent. However, little is known about the developmental role of activity in the other major cortical population of neurons, the GABA-producing interneurons. These neurons are morphologically and functionally heterogeneous and efforts over the past decade have focused on determining the mechanisms that contribute to this diversity. It was recently discovered that 30\% of all cortical interneurons arise from a relatively novel source within the ventral telencephalon, the caudal ganglionic eminence (CGE). Owing to their late birth date, these interneurons populate the cortex only after the majority of other interneurons and pyramidal cells are already in place and have started to functionally integrate. Here we demonstrate in mice that for CGE-derived reelin (Re)-positive and calretinin (Cr)-positive (but not vasoactive intestinal peptide (VIP)-positive) interneurons, activity is essential before postnatal day 3 for correct migration, and that after postnatal day 3, glutamate-mediated activity controls the development of their axons and dendrites. Furthermore, we show that the engulfment and cell motility 1 gene (Elmo1), a target of the transcription factor distal-less homeobox 1 (Dlx1), is selectively expressed in Re(+) and Cr(+) interneurons and is both necessary and sufficient for activity-dependent interneuron migration. Our findings reveal a selective requirement for activity in shaping the cortical integration of specific neuronal subtypes.}, Author = {De Marco Garc{\'\i}a, Natalia V and Karayannis, Theofanis and Fishell, Gord}, Date-Added = {2011-08-16 16:33:31 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {development; Spontaneous activity; Neocortex; GABA; Interneurons; 21 Activity-development}, Mesh = {Adaptor Proteins, Signal Transducing; Animals; Calcium-Binding Protein, Vitamin D-Dependent; Cell Adhesion Molecules, Neuronal; Cell Movement; Cell Shape; Cerebral Cortex; Extracellular Matrix Proteins; Female; Gene Expression Regulation; Homeodomain Proteins; Interneurons; Mice; Nerve Tissue Proteins; Potassium Channels, Inwardly Rectifying; Pregnancy; Pyramidal Cells; Receptors, Ionotropic Glutamate; Serine Endopeptidases; Signal Transduction; Transcription Factors; Vasoactive Intestinal Peptide}, Month = {Apr}, Number = {7343}, Pages = {351-5}, pmid = {21460837}, Pst = {ppublish}, Title = {Neuronal activity is required for the development of specific cortical interneuron subtypes}, Volume = {472}, Year = {2011}, url = {papers/DeMarcoGarcía_Nature2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature09865}} @article{Han:2011, Abstract = {Technologies for silencing the electrical activity of genetically targeted neurons in the brain are important for assessing the contribution of specific cell types and pathways toward behaviors and pathologies. Recently we found that archaerhodopsin-3 from Halorubrum sodomense (Arch), a light-driven outward proton pump, when genetically expressed in neurons, enables them to be powerfully, transiently, and repeatedly silenced in response to pulses of light. Because of the impressive characteristics of Arch, we explored the optogenetic utility of opsins with high sequence homology to Arch, from archaea of the Halorubrum genus. We found that the archaerhodopsin from Halorubrum strain TP009, which we named ArchT, could mediate photocurrents of similar maximum amplitude to those of Arch (∼900 pA in vitro), but with a >3-fold improvement in light sensitivity over Arch, most notably in the optogenetic range of 1-10 mW/mm(2), equating to >2× increase in brain tissue volume addressed by a typical single optical fiber. Upon expression in mouse or rhesus macaque cortical neurons, ArchT expressed well on neuronal membranes, including excellent trafficking for long distances down neuronal axons. The high light sensitivity prompted us to explore ArchT use in the cortex of the rhesus macaque. Optical perturbation of ArchT-expressing neurons in the brain of an awake rhesus macaque resulted in a rapid and complete (∼100\%) silencing of most recorded cells, with suppressed cells achieving a median firing rate of 0 spikes/s upon illumination. A small population of neurons showed increased firing rates at long latencies following the onset of light stimulation, suggesting the existence of a mechanism of network-level neural activity balancing. The powerful net suppression of activity suggests that ArchT silencing technology might be of great use not only in the causal analysis of neural circuits, but may have therapeutic applications.}, Author = {Han, Xue and Chow, Brian Y and Zhou, Huihui and Klapoetke, Nathan C and Chuong, Amy and Rajimehr, Reza and Yang, Aimei and Baratta, Michael V and Winkle, Jonathan and Desimone, Robert and Boyden, Edward S}, Date-Added = {2011-08-16 16:31:40 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Front Syst Neurosci}, Journal-Full = {Frontiers in systems neuroscience}, Keywords = {optogenetics; frontiers review; activity manipulation; Primates; Genetic Engineering; Gene Transfer Techniques}, Pages = {18}, Pmc = {PMC3082132}, pmid = {21811444}, Pst = {ppublish}, Title = {A high-light sensitivity optical neural silencer: development and application to optogenetic control of non-human primate cortex}, Volume = {5}, Year = {2011}, url = {papers/Han_FrontSystNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fnsys.2011.00018}} @article{Mazzuca:2011, Abstract = {The mechanisms controlling pain in newborns during delivery are poorly understood. We explored the hypothesis that oxytocin, an essential hormone for labor and a powerful neuromodulator, exerts analgesic actions on newborns during delivery. Using a thermal tail-flick assay, we report that pain sensitivity is two-fold lower in rat pups immediately after birth than 2 days later. Oxytocin receptor antagonists strongly enhanced pain sensitivity in newborn, but not in 2-day-old rats, whereas oxytocin reduced pain at both ages suggesting an endogenous analgesia by oxytocin during delivery. Similar analgesic effects of oxytocin, measured as attenuation of pain-vocalization induced by electrical whisker pad stimulation, were also observed in decerebrated newborns. Oxytocin reduced GABA-evoked calcium responses and depolarizing GABA driving force in isolated neonatal trigeminal neurons suggesting that oxytocin effects are mediated by alterations of intracellular chloride. Unlike GABA signaling, oxytocin did not affect responses mediated by P2X3 and TRPV1 receptors. In keeping with a GABAergic mechanism, reduction of intracellular chloride by the diuretic NKCC1 chloride co-transporter antagonist bumetanide mimicked the analgesic actions of oxytocin and its effects on GABA responses in nociceptive neurons. Therefore, endogenous oxytocin exerts an analgesic action in newborn pups that involves a reduction of the depolarizing action of GABA on nociceptive neurons. Therefore, the same hormone that triggers delivery also acts as a natural pain killer revealing a novel facet of the protective actions of oxytocin in the fetus at birth.}, Author = {Mazzuca, Michel and Minlebaev, Marat and Shakirzyanova, Anastasia and Tyzio, Roman and Taccola, Giuliano and Janackova, Sona and Gataullina, Svetlana and Ben-Ari, Yehezkel and Giniatullin, Rashid and Khazipov, Rustem}, Date-Added = {2011-08-16 16:29:32 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Front Cell Neurosci}, Journal-Full = {Frontiers in cellular neuroscience}, Keywords = {development; GABA; Neocortex; neonatal; Newborn; Oxytocin/antagonists &inhibitors/pharmacology; neurophysiology; Anesthesia; rat}, Pages = {3}, Pmc = {PMC3080614}, pmid = {21519396}, Pst = {epublish}, Title = {Newborn Analgesia Mediated by Oxytocin during Delivery}, Volume = {5}, Year = {2011}, url = {papers/Mazzuca_FrontCellNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncel.2011.00003}} @article{Etherton:2011, Abstract = {Multiple independent mutations in neuroligin genes were identified in patients with familial autism, including the R451C substitution in neuroligin-3 (NL3). Previous studies showed that NL3(R451C) knock-in mice exhibited modestly impaired social behaviors, enhanced water maze learning abilities, and increased synaptic inhibition in the somatosensory cortex, and they suggested that the behavioral changes in these mice may be caused by a general shift of synaptic transmission to inhibition. Here, we confirm that NL3(R451C) mutant mice behaviorally exhibit social interaction deficits and electrophysiologically display increased synaptic inhibition in the somatosensory cortex. Unexpectedly, however, we find that the NL3(R451C) mutation produced a strikingly different phenotype in the hippocampus. Specifically, in the hippocampal CA1 region, the NL3(R451C) mutation caused an ∼1.5-fold increase in AMPA receptor-mediated excitatory synaptic transmission, dramatically altered the kinetics of NMDA receptor-mediated synaptic responses, induced an approximately twofold up-regulation of NMDA receptors containing NR2B subunits, and enhanced long-term potentiation almost twofold. NL3 KO mice did not exhibit any of these changes. Quantitative light microscopy and EM revealed that the NL3(R451C) mutation increased dendritic branching and altered the structure of synapses in the stratum radiatum of the hippocampus. Thus, in NL3(R451C) mutant mice, a single point mutation in a synaptic cell adhesion molecule causes context-dependent changes in synaptic transmission; these changes are consistent with the broad impact of this mutation on murine and human behaviors, suggesting that NL3 controls excitatory and inhibitory synapse properties in a region- and circuit-specific manner.}, Author = {Etherton, Mark and F{\"o}ldy, Csaba and Sharma, Manu and Tabuchi, Katsuhiko and Liu, Xinran and Shamloo, Mehrdad and Malenka, Robert C and S{\"u}dhof, Thomas C}, Date-Added = {2011-08-16 15:22:18 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {development; Cell Adhesion Molecules; 21 Neurophysiology; circuit formation; Neocortex; Hippocampus; structural remodeling; neuroligin; Autistic Disorder; neurological disorder; mice}, Month = {Aug}, pmid = {21808020}, Pst = {aheadofprint}, Title = {Autism-linked neuroligin-3 R451C mutation differentially alters hippocampal and cortical synaptic function}, Year = {2011}, url = {papers/Etherton_ProcNatlAcadSciUSA2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1111093108}} @article{Dreosti:2011, Abstract = {Retinal bipolar cells have been assumed to generate purely graded responses to light. To test this idea we imaged the presynaptic calcium transient in live zebrafish. We found that ON, OFF, transient and sustained bipolar cells are all capable of generating fast 'all-or-none' calcium transients modulated by visual stimulation.}, Author = {Dreosti, Elena and Esposti, Federico and Baden, Tom and Lagnado, Leon}, Date-Added = {2011-07-26 13:12:14 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {optical physiology; optical imaging; calcium imaging; microscopy; in vivo; Technique; multiphoton; Zebrafish; retina; bipolar cells; visual system; 21 Neurophysiology; development}, Month = {Jun}, pmid = {21706020}, Pst = {aheadofprint}, Title = {In vivo evidence that retinal bipolar cells generate spikes modulated by light}, Year = {2011}, url = {papers/Dreosti_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2841}} @article{Hofer:2011, Abstract = {Neuronal responses during sensory processing are influenced by both the organization of intracortical connections and the statistical features of sensory stimuli. How these intrinsic and extrinsic factors govern the activity of excitatory and inhibitory populations is unclear. Using two-photon calcium imaging in vivo and intracellular recordings in vitro, we investigated the dependencies between synaptic connectivity, feature selectivity and network activity in pyramidal cells and fast-spiking parvalbumin-expressing (PV) interneurons in mouse visual cortex. In pyramidal cell populations, patterns of neuronal correlations were largely stimulus-dependent, indicating that their responses were not strongly dominated by functionally biased recurrent connectivity. By contrast, visual stimulation only weakly modified co-activation patterns of fast-spiking PV cells, consistent with the observation that these broadly tuned interneurons received very dense and strong synaptic input from nearby pyramidal cells with diverse feature selectivities. Therefore, feedforward and recurrent network influences determine the activity of excitatory and inhibitory ensembles in fundamentally different ways.}, Author = {Hofer, Sonja B and Ko, Ho and Pichler, Bruno and Vogelstein, Joshua and Ros, Hana and Zeng, Hongkui and Lein, Ed and Lesica, Nicholas A and Mrsic-Flogel, Thomas D}, Date-Added = {2011-07-26 13:10:04 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {optical physiology; frontiers review; 21 Cortical oscillations; 21 Neurophysiology; calcium imaging; multiphoton; Visual Cortex; visual system; mouse; microscopy; read; Technique}, Month = {Jul}, pmid = {21765421}, Pst = {aheadofprint}, Title = {Differential connectivity and response dynamics of excitatory and inhibitory neurons in visual cortex}, Year = {2011}, url = {papers/Hofer_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2876}} @article{Blasi:2011, Abstract = {Human voices play a fundamental role in social communication, and areas of the adult "social brain" show specialization for processing voices and their emotional content (superior temporal sulcus, inferior prefrontal cortex, premotor cortical regions, amygdala, and insula) [1-8]. However, it is unclear when this specialization develops. Functional magnetic resonance (fMRI) studies suggest that the infant temporal cortex does not differentiate speech from music or backward speech [9, 10], but a prior study with functional near-infrared spectroscopy revealed preferential activation for human voices in 7-month-olds, in a more posterior location of the temporal cortex than in adults [11]. However, the brain networks involved in processing nonspeech human vocalizations in early development are still unknown. To address this issue, in the present fMRI study, 3- to 7-month-olds were presented with adult nonspeech vocalizations (emotionally neutral, emotionally positive, and emotionally negative) and nonvocal environmental sounds. Infants displayed significant differential activation in the anterior portion of the temporal cortex, similarly to adults [1]. Moreover, sad vocalizations modulated the activity of brain regions involved in processing affective stimuli such as the orbitofrontal cortex [12] and insula [7, 8]. These results suggest remarkably early functional specialization for processing human voice and negative emotions.}, Author = {Blasi, Anna and Mercure, Evelyne and Lloyd-Fox, Sarah and Thomson, Alex and Brammer, Michael and Sauter, Disa and Deeley, Quinton and Barker, Gareth J and Renvall, Ville and Deoni, Sean and Gasston, David and Williams, Steven C R and Johnson, Mark H and Simmons, Andrew and Murphy, Declan G M}, Date-Added = {2011-07-26 13:07:57 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {21 Activity-development; Imaging; fmri; infant; human; Neocortex; Sensory/physiology; sensory map; Environment; development}, Month = {Jul}, Number = {14}, Pages = {1220-4}, pmid = {21723130}, Pst = {ppublish}, Title = {Early specialization for voice and emotion processing in the infant brain}, Volume = {21}, Year = {2011}, url = {papers/Blasi_CurrBiol2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2011.06.009}} @article{Thut:2011, Abstract = {Neuronal elements underlying perception, cognition, and action exhibit distinct oscillatory phenomena, measured in humans by electro- or magnetoencephalography (EEG/MEG). So far, the correlative or causal nature of the link between brain oscillations and functions has remained elusive. A compelling demonstration of causality would primarily generate oscillatory signatures that are known to correlate with particular cognitive functions and then assess the behavioral consequences. Here, we provide the first direct evidence for causal entrainment of brain oscillations by transcranial magnetic stimulation (TMS) using concurrent EEG.}, Author = {Thut, Gregor and Veniero, Domenica and Romei, Vincenzo and Miniussi, Carlo and Schyns, Philippe and Gross, Joachim}, Date-Added = {2011-07-26 13:05:45 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {entrainment; 21 Cortical oscillations; 21 Neurophysiology; Theoretical; Stimulation}, Month = {Jul}, Number = {14}, Pages = {1176-85}, pmid = {21723129}, Pst = {ppublish}, Title = {Rhythmic TMS causes local entrainment of natural oscillatory signatures}, Volume = {21}, Year = {2011}, url = {papers/Thut_CurrBiol2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2011.05.049}} @article{Mittmann:2011, Abstract = {Multiphoton imaging (MPI) is widely used for recording activity simultaneously from many neurons in superficial cortical layers in vivo. We combined regenerative amplification multiphoton microscopy (RAMM) with genetically encoded calcium indicators to extend MPI of neuronal population activity into layer 5 (L5) of adult mouse somatosensory cortex. We found that this approach could be used to record and quantify spontaneous and sensory-evoked activity in populations of L5 neuronal somata located as much as 800 μm below the pia. In addition, we found that RAMM could be used to simultaneously image activity from large (∼80) populations of apical dendrites and follow these dendrites down to their somata of origin.}, Author = {Mittmann, Wolfgang and Wallace, Damian J and Czubayko, Uwe and Herb, Jan T and Schaefer, Andreas T and Looger, Loren L and Denk, Winfried and Kerr, Jason N D}, Date-Added = {2011-07-26 13:02:23 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Cortical oscillations; 21 Neurophysiology; Neocortex; Technique; calcium imaging; microscopy; multiphoton; Pyramidal Cells; Reporter/genetics; layer 5; optical physiology; frontiers review; adult; mouse; read}, Month = {Jul}, pmid = {21743473}, Pst = {aheadofprint}, Title = {Two-photon calcium imaging of evoked activity from L5 somatosensory neurons in vivo}, Year = {2011}, url = {papers/Mittmann_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2879}} @article{Tallini:2006, Abstract = {Genetically encoded sensor proteins provide unique opportunities to advance the understanding of complex cellular interactions in physiologically relevant contexts; however, previously described sensors have proved to be of limited use to report cell signaling in vivo in mammals. Here, we describe an improved Ca(2+) sensor, GCaMP2, its inducible expression in the mouse heart, and its use to examine signaling in heart cells in vivo. The high brightness and stability of GCaMP2 enable the measurement of myocyte Ca(2+) transients in all regions of the beating mouse heart and prolonged pacing and mapping studies in isolated, perfused hearts. Transgene expression is efficiently temporally regulated in cardiomyocyte GCaMP2 mice, allowing recording of in vivo signals 4 weeks after transgene induction. High-resolution imaging of Ca(2+) waves in GCaMP2-expressing embryos revealed key aspects of electrical conduction in the preseptated heart. At embryonic day (e.d.) 10.5, atrial and ventricular conduction occur rapidly, consistent with the early formation of specialized conduction pathways. However, conduction is markedly slowed through the atrioventricular canal in the e.d. 10.5 heart, forming the basis for an effective atrioventricular delay before development of the AV node, as rapid ventricular activation occurs after activation of the distal AV canal tissue. Consistent with the elimination of the inner AV canal muscle layer at e.d. 13.5, atrioventricular conduction through the canal was abolished at this stage. These studies demonstrate that GCaMP2 will have broad utility in the dissection of numerous complex cellular interactions in mammals, in vivo.}, Author = {Tallini, Yvonne N and Ohkura, Masamichi and Choi, Bum-Rak and Ji, Guangju and Imoto, Keiji and Doran, Robert and Lee, Jane and Plan, Patricia and Wilson, Jason and Xin, Hong-Bo and Sanbe, Atsushi and Gulick, James and Mathai, John and Robbins, Jeffrey and Salama, Guy and Nakai, Junichi and Kotlikoff, Michael I}, Date-Added = {2011-07-15 15:32:51 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {frontiers review; calcium imaging; heart; Genetic Techniques; gene; 21 Neurophysiology}, Mesh = {Amino Acid Sequence; Animals; Atrioventricular Node; Calcium; Calcium Signaling; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases; Embryo, Mammalian; Green Fluorescent Proteins; Mice; Mice, Transgenic; Molecular Sequence Data; Myocardial Reperfusion; Myocardium; Myocytes, Cardiac; Spectrometry, Fluorescence}, Month = {Mar}, Number = {12}, Pages = {4753-8}, Pmc = {PMC1450242}, pmid = {16537386}, Pst = {ppublish}, Title = {Imaging cellular signals in the heart in vivo: Cardiac expression of the high-signal Ca2+ indicator GCaMP2}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0509378103}} @article{Bonifazi:2009, Abstract = {Brain function operates through the coordinated activation of neuronal assemblies. Graph theory predicts that scale-free topologies, which include "hubs" (superconnected nodes), are an effective design to orchestrate synchronization. Whether hubs are present in neuronal assemblies and coordinate network activity remains unknown. Using network dynamics imaging, online reconstruction of functional connectivity, and targeted whole-cell recordings in rats and mice, we found that developing hippocampal networks follow a scale-free topology, and we demonstrated the existence of functional hubs. Perturbation of a single hub influenced the entire network dynamics. Morphophysiological analysis revealed that hub cells are a subpopulation of gamma-aminobutyric acid-releasing (GABAergic) interneurons possessing widespread axonal arborizations. These findings establish a central role for GABAergic interneurons in shaping developing networks and help provide a conceptual framework for studying neuronal synchrony.}, Author = {Bonifazi, P and Goldin, M and Picardo, M A and Jorquera, I and Cattani, A and Bianconi, G and Represa, A and Ben-Ari, Y and Cossart, R}, Date-Added = {2011-07-15 14:14:02 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {frontiers review; 21 Neurophysiology; 21 Activity-development; 21 Calcium imaging; network; Theoretical; Imaging; microscopy; development; Hippocampus; GABA}, Mesh = {Action Potentials; Animals; Axons; CA3 Region, Hippocampal; Calcium; Dendrites; Excitatory Postsynaptic Potentials; Hippocampus; Interneurons; Mice; Nerve Net; Patch-Clamp Techniques; Pyramidal Cells; Rats; Rats, Wistar; Synapses; gamma-Aminobutyric Acid}, Month = {Dec}, Number = {5958}, Pages = {1419-24}, pmid = {19965761}, Pst = {ppublish}, Title = {GABAergic hub neurons orchestrate synchrony in developing hippocampal networks}, Volume = {326}, Year = {2009}, url = {papers/Bonifazi_Science2009.pdf}, Bdsk-File-2 = {papers/Bonifazi_Science2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1175509}} @article{Sorensen:2002, Abstract = {Synchronous neurotransmission depends on the tight coupling between Ca(2+) influx and fusion of neurotransmitter-filled vesicles with the plasma membrane. The vesicular soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein synaptobrevin 2 and the plasma membrane SNAREs syntaxin 1 and synaptosomal protein of 25 kDa (SNAP-25) are essential for calcium-triggered exocytosis. However, the link between calcium triggering and SNARE function remains elusive. Here we describe mutations in two sites on the surface of the SNARE complex formed by acidic and hydrophilic residues of SNAP-25 and synaptobrevin 2, which were found to coordinate divalent cations in the neuronal SNARE complex crystal structure. By reducing the net charge of the site in SNAP-25 we identify a mutation that interferes with calcium triggering of exocytosis when overexpressed in chromaffin cells. Exocytosis was elicited by photorelease of calcium from a calcium cage and evaluated by using patch-clamp capacitance measurements at millisecond time resolution. We present a method for monitoring the dependence of exocytotic rate upon calcium concentration at the release site and demonstrate that the mutation decreased the steepness of this relationship, indicating that the number of sequential calcium-binding steps preceding exocytosis is reduced by one. We conclude that the SNARE complex is linked directly to calcium triggering of exocytosis, most likely in a complex with auxiliary proteins.}, Author = {S{\o}rensen, Jakob B and Matti, Ulf and Wei, Shun-Hui and Nehring, Ralf B and Voets, Thomas and Ashery, Uri and Binz, Thomas and Neher, Erwin and Rettig, Jens}, Date-Added = {2011-07-15 12:42:02 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {frontiers review; 21 Neurophysiology; Technique; synapses; activity manipulation}, Mesh = {Amino Acid Substitution; Animals; Calcium; Calcium Signaling; Exocytosis; Green Fluorescent Proteins; Kinetics; Luminescent Proteins; Membrane Proteins; Models, Molecular; Mutagenesis, Site-Directed; Nerve Tissue Proteins; Plasmids; Protein Conformation; R-SNARE Proteins; Rats; Recombinant Fusion Proteins; Synaptosomal-Associated Protein 25}, Month = {Feb}, Number = {3}, Pages = {1627-32}, Pmc = {PMC122241}, pmid = {11830673}, Pst = {ppublish}, Title = {The SNARE protein SNAP-25 is linked to fast calcium triggering of exocytosis}, Volume = {99}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.251673298}} @article{Chen:2003d, Abstract = {Modulatory projections from brainstem nuclei and intrinsic thalamic interneurons play a significant role in modifying sensory information as it is relayed from the thalamus to the cortex. In the lateral geniculate nucleus (LGN), neurotransmitters released from these modulatory inputs can affect the intrinsic conductances of thalamocortical relay neurons, thus altering their firing properties. Here, we show that in addition to postsynaptic effects, neuromodulators such as serotonin (5-HT) and GABA can act presynaptically to regulate neurotransmitter release at the synapse between retinal ganglion cells (RGCs) and relay neurons in the LGN, the retinogeniculate synapse. Activation of 5HT1 and GABA(B) receptors significantly decreased EPSC amplitude. This inhibition was accompanied by a decrease in the extent of paired-pulse depression, suggesting that it is presynaptic in origin. In addition, fluorometric calcium measurements from retinal axon terminals labeled with Calcium Green-1 dextran revealed that 5HT1 and GABA(B) receptor agonists decreased presynaptic calcium influx. Taken together, our data indicate that serotonin and GABA can act presynaptically to decrease calcium influx at the retinogeniculate synapse and modify transmission of visual information in the LGN.}, Author = {Chen, Chinfei and Regehr, Wade G}, Date-Added = {2011-07-15 11:39:07 -0400}, Date-Modified = {2011-07-15 11:40:31 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Calcium imaging; 21 Circuit structure-function; 21 Neurophysiology; retina; LGN; imaging; microscopy; Technique; retinal wave paper; frontiers review}, Mesh = {Animals; Calcium; Excitatory Postsynaptic Potentials; Extracellular Space; Fluorescent Dyes; GABA Agonists; GABA Antagonists; GABA-A Receptor Antagonists; GABA-B Receptor Agonists; GABA-B Receptor Antagonists; Geniculate Bodies; Mice; Patch-Clamp Techniques; Presynaptic Terminals; Retina; Retinal Ganglion Cells; Serotonin; Serotonin Agents; Synapses; Synaptic Transmission; Visual Pathways; gamma-Aminobutyric Acid}, Month = {Apr}, Number = {8}, Pages = {3130-5}, pmid = {12716920}, Pst = {ppublish}, Title = {Presynaptic modulation of the retinogeniculate synapse}, Volume = {23}, Year = {2003}, url = {papers/Chen_JNeurosci2003.pdf}} @article{Grinberg:2011, Abstract = {Spreading depression (SD) is thought to cause migraine aura, and perhaps migraine, and includes a transient loss of synaptic activity preceded and followed by increased neuronal excitability. Activated microglia influence neuronal activity and play an important role in homeostatic synaptic scaling via release of cytokines. Furthermore, enhanced neuronal function activates microglia to not only secrete cytokines but also to increase the motility of their branches, with somata remaining stationary. While SD also increases the release of cytokines from microglia, the effects on microglial movement from its synaptic activity fluctuations are unknown. Accordingly, we used time-lapse imaging of rat hippocampal slice cultures to probe for microglial movement associated with SD. We observed that in uninjured brain whole microglial cells moved. The movements were well described by the type of L{\'e}vy flight known to be associated with an optimal search pattern. Hours after SD, when synaptic activity rose, microglial cell movement was significantly increased. To test how synaptic activity influenced microglial movement, we enhanced neuronal activity with chemical long-term potentiation or LPS and abolished it with TTX. We found that microglial movement was significantly decreased by enhanced neuronal activity and significantly increased by activity blockade. Finally, application of glutamate and ATP to mimic restoration of synaptic activity in the presence of TTX stopped microglial movement that was otherwise seen with TTX. Thus, synaptic activity retains microglial cells in place and an absence of synaptic activity sends them off to influence wider expanses of brain. Perhaps increased microglial movements after SD are a long-lasting, and thus maladaptive, response in which these cells increase neuronal activity via contact or paracrine signaling, which results in increased susceptibility of larger brain areas to SD. If true, then targeting mechanisms that retard activity-dependent microglial L{\'e}vy flights may be a novel means to reduce susceptibility to migraine.}, Author = {Grinberg, Yelena Y and Milton, John G and Kraig, Richard P}, Date-Added = {2011-05-20 12:02:04 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {PLoS One}, Journal-Full = {PloS one}, Number = {4}, Pages = {e19294}, Pmc = {PMC3082564}, pmid = {21541289}, Pst = {epublish}, Title = {Spreading depression sends microglia on l{\'e}vy flights}, Volume = {6}, Year = {2011}, url = {papers/Grinberg_PLoSOne2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0019294}} @article{Muller:1988, Abstract = {We traced the retino-retinal projection with Rhodamine B isothiocyanate (RITC), Rhodamin labelled latex microspheres (RLM), horseradish peroxidase (HRP) and choleratoxin conjugated horseradish peroxidase (BHRP). The number and distribution of ganglion cells projecting to the contralateral eye were recorded. Newborn and young rats have up to about 130 ganglion cells projecting to the other retina; this confirms previous findings. We extended these findings in two ways. First, we describe a similar projection in rabbits consisting of fewer cells; second, we describe the persistence of a small component of this projection into adulthood. In addition we show with RITC and Nuclear Yellow double tracing that some of the retino-retinal ganglion cells have an axon collateral which projects to the superior colliculus. We performed control experiments in order to exclude spillover of tracer which might produce false positive labelling.}, Author = {M{\"u}ller, M and Holl{\"a}nder, H}, Date-Added = {2011-05-02 11:07:54 -0400}, Date-Modified = {2011-05-02 11:09:27 -0400}, Journal = {Exp Brain Res}, Journal-Full = {Experimental brain research. Experimentelle Hirnforschung. Exp{\'e}rimentation c{\'e}r{\'e}brale}, Keywords = {connectivity; retinal wave paper; Retina; visual system; Superior Colliculus; retinopetal; Retinal Ganglion Cells; retinal projections}, Mesh = {Animals; Animals, Newborn; Fluorescent Dyes; Functional Laterality; Horseradish Peroxidase; Rabbits; Rats; Rats, Inbred Strains; Retina; Retinal Ganglion Cells; Species Specificity}, Number = {3}, Pages = {611-7}, pmid = {3416972}, Pst = {ppublish}, Title = {A small population of retinal ganglion cells projecting to the retina of the other eye. An experimental study in the rat and the rabbit}, Volume = {71}, Year = {1988}, url = {papers/Müller_ExpBrainRes1988.pdf}} @article{Arp:2008, Abstract = {As part of a series of workshops on different aspects of biomedical ontology sponsored by the National Center for Biomedical Ontology (NCBO), a workshop titled "Ontologies of Cellular Networks" took place in Newark, New Jersey, on 27 to 28 March 2008. This workshop included more than 30 participants from various backgrounds in biomedicine and bioinformatics. The goal of the workshop was to provide an introduction to the basic tools and methods of ontology, as well as to enhance coordination between groups already working on ontologies of cellular networks. The meeting focused on three questions: What is an ontology? What is a pathway? What is a cellular network?}, Author = {Arp, Robert and Smith, Barry}, Date-Added = {2011-04-25 14:16:01 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Sci Signal}, Journal-Full = {Science signaling}, Keywords = {neuroinformatics; 20 Networks; Theoretical; Computational Biology; connectivity;}, Mesh = {Cell Communication; Signal Transduction; Systems Biology; Terminology as Topic}, Number = {50}, Pages = {mr2}, pmid = {19091693}, Pst = {epublish}, Title = {Ontologies of cellular networks}, Volume = {1}, Year = {2008}, url = {papers/Arp_SciSignal2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/scisignal.150mr2}} @article{Petilla-Interneuron-Nomenclature-Group:2008, Abstract = {Neuroscience produces a vast amount of data from an enormous diversity of neurons. A neuronal classification system is essential to organize such data and the knowledge that is derived from them. Classification depends on the unequivocal identification of the features that distinguish one type of neuron from another. The problems inherent in this are particularly acute when studying cortical interneurons. To tackle this, we convened a representative group of researchers to agree on a set of terms to describe the anatomical, physiological and molecular features of GABAergic interneurons of the cerebral cortex. The resulting terminology might provide a stepping stone towards a future classification of these complex and heterogeneous cells. Consistent adoption will be important for the success of such an initiative, and we also encourage the active involvement of the broader scientific community in the dynamic evolution of this project.}, Author = {{Petilla Interneuron Nomenclature Group} and Ascoli, Giorgio A and Alonso-Nanclares, Lidia and Anderson, Stewart A and Barrionuevo, German and Benavides-Piccione, Ruth and Burkhalter, Andreas and Buzs{\'a}ki, Gy{\"o}rgy and Cauli, Bruno and Defelipe, Javier and Fair{\'e}n, Alfonso and Feldmeyer, Dirk and Fishell, Gord and Fregnac, Yves and Freund, Tamas F and Gardner, Daniel and Gardner, Esther P and Goldberg, Jesse H and Helmstaedter, Moritz and Hestrin, Shaul and Karube, Fuyuki and Kisv{\'a}rday, Zolt{\'a}n F and Lambolez, Bertrand and Lewis, David A and Marin, Oscar and Markram, Henry and Mu{\~n}oz, Alberto and Packer, Adam and Petersen, Carl C H and Rockland, Kathleen S and Rossier, Jean and Rudy, Bernardo and Somogyi, Peter and Staiger, Jochen F and Tamas, Gabor and Thomson, Alex M and Toledo-Rodriguez, Maria and Wang, Yun and West, David C and Yuste, Rafael}, Date-Added = {2011-04-25 14:12:51 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {neuroinformatics; 20 Networks; Theoretical; Computational Biology; Neocortex; Interneurons; GABA}, Mesh = {Action Potentials; Axons; Cerebral Cortex; Humans; Interneurons; Synapses; gamma-Aminobutyric Acid}, Month = {Jul}, Number = {7}, Pages = {557-68}, Pmc = {PMC2868386}, pmid = {18568015}, Pst = {ppublish}, Title = {Petilla terminology: nomenclature of features of GABAergic interneurons of the cerebral cortex}, Volume = {9}, Year = {2008}, url = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008.pdf}, Bdsk-File-2 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008a.pdf}, Bdsk-File-3 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008b.pdf}, Bdsk-File-4 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008c.pdf}, Bdsk-File-5 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008d.pdf}, Bdsk-File-6 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008e.pdf}, Bdsk-File-7 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008f.pdf}, Bdsk-File-8 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008g.pdf}, Bdsk-File-9 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008h.pdf}, File0 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008i.pdf}, File1 = {papers/PetillaInterneuronNomenclatureGroup_NatRevNeurosci2008j.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2402}} @article{Douglas:1989, Author = {Douglas, Rodney J. and Martin, Kevan A. C. and Whitteridge, David}, Date-Added = {2011-04-08 13:02:04 -0400}, Date-Modified = {2011-04-08 13:06:33 -0400}, Journal = {Neural Comput}, Keywords = {neuroinformatics; visual system; visual cortex; computation biology; function; sensory map; topographic map; neurophysiology; extracellular}, Number = {4}, Pages = {480-88}, Title = {A canonical microcircuit for neocortex}, Volume = {1}, Year = {1989}, url = {papers/Douglas_NeuralComput1989.pdf}} @article{Hubel:1977a, Author = {Hubel, D H and Wiesel, T N}, Date-Added = {2011-04-08 12:52:09 -0400}, Date-Modified = {2013-06-27 12:56:03 +0000}, Journal = {Proc R Soc Lond B Biol Sci}, Journal-Full = {Proceedings of the Royal Society of London. Series B, Containing papers of a Biological character. Royal Society (Great Britain)}, Keywords = {neuroinformatics; visual system; visual cortex; computation biology; function; sensory map; topographic map; neurophysiology; extracellular; currOpinRvw}, Mesh = {Animals; Animals, Newborn; Geniculate Bodies; Haplorhini; Macaca; Species Specificity; Visual Cortex; Visual Fields; Visual Pathways; Visual Perception}, Month = {Jul}, Number = {1130}, Pages = {1-59}, pmid = {20635}, Pst = {ppublish}, Title = {Ferrier lecture. Functional architecture of macaque monkey visual cortex}, Volume = {198}, Year = {1977}, url = {papers/Hubel_ProcRSocLondBBiolSci1977.pdf}} @article{Bosking:1997, Abstract = {Horizontal connections, formed primarily by the axon collaterals of pyramidal neurons in layer 2/3 of visual cortex, extend for millimeters parallel to the cortical surface and form patchy terminations. Previous studies have provided evidence that the patches formed by horizontal connections exhibit modular specificity, preferentially linking columns of neurons with similar response characteristics, such as preferred orientation. The issue of how these connections are distributed with respect to the topographic map of visual space, however, has not been resolved. Here we combine optical imaging of intrinsic signals with small extracellular injections of biocytin to assess quantitatively the specificity of horizontal connections with respect to both the map of orientation preference and the map of visual space in tree shrew V1. Our results indicate that horizontal connections outside a radius of 500 microm from the injection site exhibit not only modular specificity, but also specificity for axis of projection. Labeled axons extend for longer distances, and give off more terminal boutons, along an axis in the map of visual space that corresponds to the preferred orientation of the injection site. Inside of 500 microm, the pattern of connections is much less specific, with boutons found along every axis, contacting sites with a wide range of preferred orientations. The system of long-range horizontal connections can be summarized as preferentially linking neurons with co-oriented, co-axially aligned receptive fields. These observations suggest specific ways that horizontal circuits contribute to the response properties of layer 2/3 neurons and to mechanisms of visual perception.}, Author = {Bosking, W H and Zhang, Y and Schofield, B and Fitzpatrick, D}, Date-Added = {2011-04-08 12:52:09 -0400}, Date-Modified = {2011-04-08 12:53:37 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {neuroinformatics; visual system; visual cortex; computation biology; function; sensory map; topographic map; neurophysiology; extracellular}, Mesh = {Animals; Corpus Striatum; Shrews; Visual Cortex; Visual Pathways}, Month = {Mar}, Number = {6}, Pages = {2112-27}, pmid = {9045738}, Pst = {ppublish}, Title = {Orientation selectivity and the arrangement of horizontal connections in tree shrew striate cortex}, Volume = {17}, Year = {1997}, url = {papers/Bosking_JNeurosci1997.pdf}} @article{Sompolinsky:1997, Abstract = {Since the discovery of orientation selectivity by Hubel and Wiesel, the mechanisms responsible for this remarkable operation in the visual cortex have been controversial. Experimental studies over the past year have highlighted the contribution of feedforward thalamo-cortical afferents, as proposed originally by Hubel and Wiesel, but they have also indicated that this contribution alone is insufficient to account for the sharp orientation tuning observed in the visual cortex. Recent advances in understanding the functional architecture of local cortical circuitry have led to new proposals for the involvement of intracortical recurrent excitation and inhibition in orientation selectivity. Establishing how these two mechanisms work together remains an important experimental and theoretical challenge.}, Author = {Sompolinsky, H and Shapley, R}, Date-Added = {2011-04-08 12:52:09 -0400}, Date-Modified = {2011-04-08 12:53:37 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {neuroinformatics; visual system; visual cortex; computation biology; function; sensory map; topographic map; neurophysiology; extracellular}, Mesh = {Animals; Geniculate Bodies; Humans; Models, Neurological; Orientation; Space Perception; Visual Cortex}, Month = {Aug}, Number = {4}, Pages = {514-22}, pmid = {9287203}, Pst = {ppublish}, Title = {New perspectives on the mechanisms for orientation selectivity}, Volume = {7}, Year = {1997}, url = {papers/Sompolinsky_CurrOpinNeurobiol1997.pdf}} @article{Miller:2003, Abstract = {This paper reviews theoretical and experimental results on the processing of layer 4, the input-recipient layer, of cat primary visual cortex (V1). A wide range of experimental data can be understood from a model in which response tuning of layer 4 cells is largely determined by a local interplay of feedforward excitation (from thalamus) and feedforward inhibition (from layer 4 inhibitory interneurons driven by thalamus). Feedforward inhibition dominates excitation, inherits its tuning from the thalamic input and sharpens the tuning of excitatory cells. At least a strong component of the feedforward inhibition received by a cell is spatially opponent to the excitation it receives, meaning that inhibition is driven by dark in regions of the visual field in which excitation is driven by light, and vice versa. The idea of opponent inhibition can be generalized to mean inhibition driven by input patterns that are strongly anti-correlated with the patterns that excite a cell. This paper argues that dominant feedforward opponent inhibition may be a general principle of cortical layer 4. This leads to the suggestion that the properties that show columnar organization--invariance across the vertical depth of cortex--may be properties that are shared by 'opposite' (anticorrelated) stimulus pairs. This contrasts with the more common idea that a column represents a set of cells that all share similar stimulus preferences.}, Author = {Miller, Kenneth D}, Date-Added = {2011-04-08 12:52:09 -0400}, Date-Modified = {2011-04-08 12:53:37 -0400}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {neuroinformatics; visual system; visual cortex; computation biology; function; sensory map; topographic map; neurophysiology; extracellular}, Mesh = {Animals; Cats; Evoked Potentials, Visual; Feedback; Interneurons; Models, Neurological; Nerve Net; Neural Inhibition; Thalamus; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Jan}, Number = {1}, Pages = {73-82}, pmid = {12466218}, Pst = {ppublish}, Title = {Understanding layer 4 of the cortical circuit: a model based on cat V1}, Volume = {13}, Year = {2003}, url = {papers/Miller_CerebCortex2003.pdf}} @article{Ben-Shahar:2004, Abstract = {Neurons in primary visual cortex respond selectively to oriented stimuli such as edges and lines. The long-range horizontal connections between them are thought to facilitate contour integration. While many physiological and psychophysical findings suggest that collinear or association field models of good continuation dictate particular projection patterns of horizontal connections to guide this integration process, significant evidence of interactions inconsistent with these hypotheses is accumulating. We first show that natural random variations around the collinear and association field models cannot account for these inconsistencies, a fact that motivates the search for more principled explanations. We then develop a model of long-range projection fields that formalizes good continuation based on differential geometry. The analysis implicates curvature(s) in a fundamental way, and the resulting model explains both consistent data and apparent outliers. It quantitatively predicts the (typically ignored) spread in projection distribution, its nonmonotonic variance, and the differences found among individual neurons. Surprisingly, and for the first time, this model also indicates that texture (and shading) continuation can serve as alternative and complementary functional explanations to contour integration. Because current anatomical data support both (curve and texture) integration models equally and because both are important computationally, new testable predictions are derived to allow their differentiation and identification.}, Author = {Ben-Shahar, Ohad and Zucker, Steven}, Date-Added = {2011-04-08 12:52:09 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Neural Comput}, Journal-Full = {Neural computation}, Keywords = {neuroinformatics; visual system; visual cortex; computation biology; function; sensory map; topographic map; neurophysiology; extracellular}, Mesh = {Animals; Computer Simulation; Humans; Neural Networks (Computer); Neurons; Orientation; Photic Stimulation; Projection; Random Allocation; Retina; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Mar}, Number = {3}, Pages = {445-76}, pmid = {15006089}, Pst = {ppublish}, Title = {Geometrical computations explain projection patterns of long-range horizontal connections in visual cortex}, Volume = {16}, Year = {2004}, url = {papers/Ben-Shahar_NeuralComput2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1162/089976604772744866}} @article{Zacharias:2000, Abstract = {Signal transduction research has made some glowing progress in the past 12 months. Recent advances in fluorescent proteins, small molecule fluorophores and imaging technology are generating new ways to investigate signal transduction.}, Author = {Zacharias, D A and Baird, G S and Tsien, R Y}, Date-Added = {2011-04-08 10:16:39 -0400}, Date-Modified = {2011-04-08 10:16:58 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Animals; Green Fluorescent Proteins; Indicators and Reagents; Luminescent Proteins; Neurons; Neurosciences; Signal Transduction}, Month = {Jun}, Number = {3}, Pages = {416-21}, pmid = {10851181}, Pst = {ppublish}, Title = {Recent advances in technology for measuring and manipulating cell signals}, Volume = {10}, Year = {2000}, url = {papers/Zacharias_CurrOpinNeurobiol2000.pdf}} @article{Tsien:1980, Abstract = {A new family of high-affinity buffers and optical indicators for Ca2+ is rationally designed and synthesized. The parent compound is 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA), a relative of the well-known chelator EGTA [ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid] in which methylene links between oxygen and nitrogen are replaced by benzene rings. BAPTA and its derivatives share the high (greater than 10(5)) selectivity for Ca2+ over Mg2+ of EGTA but are very much less affected by pH changes and are faster at taking up and releasing Ca2+. The affinity of the parent compound for Ca2+ (dissociation constant 1.1 x 10(-7) M in 0.1 M KCl) may be strengthened or weakened by electron-releasing or -withdrawing substituents on the aromatic rings. The Ca2+ and Mg2+ affinities may further be altered by replacing the ether oxygens by heterocyclic nitrogen atoms. The compounds described are fluorescent Ca2+ indicators absorbing in the ultraviolet region; the very large spectral shifts observed on binding Ca2+ fit the prediction that complexation should hinder the conjugation of the nitrogen lone-pair electrons with the aromatic rings. Derivatives with quinoline nuclei are notable for their high sensitivity of fluorescent quantum yield to the binding of Ca2+ but not of Mg2+. Preliminary biological tests have so far revealed little or no binding to membranes or toxic effects following intracellular microinjection.}, Author = {Tsien, R Y}, Date-Added = {2011-04-08 10:06:20 -0400}, Date-Modified = {2011-04-08 10:15:44 -0400}, Journal = {Biochemistry}, Journal-Full = {Biochemistry}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Calcium; Egtazic Acid; Ethylene Glycols; Indicators and Reagents; Magnesium; Methods; Spectrophotometry, Ultraviolet; Structure-Activity Relationship}, Month = {May}, Number = {11}, Pages = {2396-404}, pmid = {6770893}, Pst = {ppublish}, Title = {New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures}, Volume = {19}, Year = {1980}, url = {papers/Tsien_Biochemistry1980.pdf}} @article{Tsien:1981, Abstract = {Present methods for measuring or buffering intracellular free calcium concentrations are almost entirely limited to robust and well anchored cells which can tolerate insertion of ion-selective microelectrodes or microinjection of calcium indicators or buffers into one cell at a time. A very few types of small cells can be loaded with buffers or indicators during controlled lysis, but such procedures grossly perturb membrane integrity and soluble cytoplasmic constituents. Liposome fusion releases only trace quantities of the trapped solute into the cytoplasm and incorporates foreign lipid into the target cell membranes. I now describe a simple technique which loads Ca2+-selective chelators into the cytoplasm of intact cells in suspension and avoids the disadvantages of previous methods. The chelators are made temporarily membrane permeable by masking their four carboxylates with special esterifying groups which then hydrolyse inside the cells, regenerating and trapping the original chelators. The method is demonstrated on red cells, mast cells and lymphocytes.}, Author = {Tsien, R Y}, Date-Added = {2011-04-08 10:06:14 -0400}, Date-Modified = {2011-04-08 10:16:04 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Buffers; Calcium; Cell Membrane; Cell Membrane Permeability; Chelating Agents; Cytoplasm; Erythrocyte Membrane; Glycine; Humans; Lymphocytes; Mast Cells}, Month = {Apr}, Number = {5806}, Pages = {527-8}, pmid = {7219539}, Pst = {ppublish}, Title = {A non-disruptive technique for loading calcium buffers and indicators into cells}, Volume = {290}, Year = {1981}} @article{Grynkiewicz:1985, Abstract = {A new family of highly fluorescent indicators has been synthesized for biochemical studies of the physiological role of cytosolic free Ca2+. The compounds combine an 8-coordinate tetracarboxylate chelating site with stilbene chromophores. Incorporation of the ethylenic linkage of the stilbene into a heterocyclic ring enhances the quantum efficiency and photochemical stability of the fluorophore. Compared to their widely used predecessor, "quin2", the new dyes offer up to 30-fold brighter fluorescence, major changes in wavelength not just intensity upon Ca2+ binding, slightly lower affinities for Ca2+, slightly longer wavelengths of excitation, and considerably improved selectivity for Ca2+ over other divalent cations. These properties, particularly the wavelength sensitivity to Ca2+, should make these dyes the preferred fluorescent indicators for many intracellular applications, especially in single cells, adherent cell layers, or bulk tissues.}, Author = {Grynkiewicz, G and Poenie, M and Tsien, R Y}, Date-Added = {2011-04-08 10:06:10 -0400}, Date-Modified = {2011-04-08 10:16:04 -0400}, Journal = {J Biol Chem}, Journal-Full = {The Journal of biological chemistry}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Aminoquinolines; Benzofurans; Calcium; Erythrocyte Membrane; Flow Cytometry; Fluorescent Dyes; Fura-2; Humans; Hydrogen-Ion Concentration; Indoles; Magnesium; Mathematics; Spectrometry, Fluorescence; Stilbenes}, Month = {Mar}, Number = {6}, Pages = {3440-50}, pmid = {3838314}, Pst = {ppublish}, Title = {A new generation of Ca2+ indicators with greatly improved fluorescence properties}, Volume = {260}, Year = {1985}, url = {papers/Grynkiewicz_JBiolChem1985.pdf}} @article{Tsien:1989a, Author = {Tsien, R Y}, Date-Added = {2011-04-08 10:06:04 -0400}, Date-Modified = {2011-04-08 10:16:04 -0400}, Journal = {Methods Cell Biol}, Journal-Full = {Methods in cell biology}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Calcium; Chlorine; Fluorescent Dyes; Hydrogen-Ion Concentration; Indicators and Reagents; Protons; Sodium}, Pages = {127-56}, pmid = {2538708}, Pst = {ppublish}, Title = {Fluorescent indicators of ion concentrations}, Volume = {30}, Year = {1989}} @article{Tsien:1989, Author = {Tsien, R Y}, Date-Added = {2011-04-08 10:05:43 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Animals; Fluorescent Dyes; Ions; Neurons}, Pages = {227-53}, pmid = {2648950}, Pst = {ppublish}, Title = {Fluorescent probes of cell signaling}, Volume = {12}, Year = {1989}, url = {papers/Tsien_AnnuRevNeurosci1989.pdf}, eprint = {http://dx.doi.org/10.1146/annurev.ne.12.030189.001303}} @article{Tsien:1990, Author = {Tsien, R W and Tsien, R Y}, Date-Added = {2011-04-08 10:05:37 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Annu Rev Cell Biol}, Journal-Full = {Annual review of cell biology}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Animals; Calcium; Calcium Channels; Humans; Signal Transduction}, Pages = {715-60}, pmid = {2177344}, Pst = {ppublish}, Title = {Calcium channels, stores, and oscillations}, Volume = {6}, Year = {1990}, url = {papers/Tsien_AnnuRevCellBiol1990.pdf}, eprint = {http://dx.doi.org/10.1146/annurev.cb.06.110190.003435}} @article{Miyawaki:1997, Abstract = {Important Ca2+ signals in the cytosol and organelles are often extremely localized and hard to measure. To overcome this problem we have constructed new fluorescent indicators for Ca2+ that are genetically encoded without cofactors and are targetable to specific intracellular locations. We have dubbed these fluorescent indicators 'cameleons'. They consist of tandem fusions of a blue- or cyan-emitting mutant of the green fluorescent protein (GFP), calmodulin, the calmodulin-binding peptide M13, and an enhanced green- or yellow-emitting GFP. Binding of Ca2+ makes calmodulin wrap around the M13 domain, increasing the fluorescence resonance energy transfer (FRET) between the flanking GFPs. Calmodulin mutations can tune the Ca2+ affinities to measure free Ca2+ concentrations in the range 10(-8) to 10(-2) M. We have visualized free Ca2+ dynamics in the cytosol, nucleus and endoplasmic reticulum of single HeLa cells transfected with complementary DNAs encoding chimaeras bearing appropriate localization signals. Ca2+ concentration in the endoplasmic reticulum of individual cells ranged from 60 to 400 microM at rest, and 1 to 50 microM after Ca2+ mobilization. FRET is also an indicator of the reversible intermolecular association of cyan-GFP-labelled calmodulin with yellow-GFP-labelled M13. Thus FRET between GFP mutants can monitor localized Ca2+ signals and protein heterodimerization in individual live cells.}, Author = {Miyawaki, A and Llopis, J and Heim, R and McCaffery, J M and Adams, J A and Ikura, M and Tsien, R Y}, Date-Added = {2011-04-08 10:05:32 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents; frontiers review}, Mesh = {Amino Acid Sequence; Calcium; Calmodulin; Cytosol; Energy Transfer; Fluorescence; Green Fluorescent Proteins; Hela Cells; Humans; Indicators and Reagents; Luminescent Proteins; Molecular Sequence Data; Mutagenesis; Myosin-Light-Chain Kinase; Peptide Fragments; Recombinant Fusion Proteins}, Month = {Aug}, Number = {6645}, Pages = {882-7}, pmid = {9278050}, Pst = {ppublish}, Title = {Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin}, Volume = {388}, Year = {1997}, url = {papers/Miyawaki_Nature1997.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/42264}} @article{Shaner:2005, Abstract = {The recent explosion in the diversity of available fluorescent proteins (FPs) promises a wide variety of new tools for biological imaging. With no unified standard for assessing these tools, however, a researcher is faced with difficult questions. Which FPs are best for general use? Which are the brightest? What additional factors determine which are best for a given experiment? Although in many cases, a trial-and-error approach may still be necessary in determining the answers to these questions, a unified characterization of the best available FPs provides a useful guide in narrowing down the options.}, Author = {Shaner, Nathan C and Steinbach, Paul A and Tsien, Roger Y}, Date-Added = {2011-04-08 10:05:27 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Animals; Fluorescent Dyes; Guidelines as Topic; Humans; Luminescent Proteins; Microscopy, Fluorescence}, Month = {Dec}, Number = {12}, Pages = {905-9}, pmid = {16299475}, Pst = {ppublish}, Title = {A guide to choosing fluorescent proteins}, Volume = {2}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth819}} @article{Palmer:2006a, Abstract = {Genetically encoded Ca2+ indicators allow researchers to quantitatively measure Ca2+ dynamics in a variety of experimental systems. This protocol summarizes the indicators that are available, and highlights those that are most appropriate for a number of experimental conditions, such as measuring Ca2+ in specific organelles and localizations in mammalian tissue-culture cells. The protocol itself focuses on the use of a cameleon, which is a fluorescence resonance-energy transfer (FRET)-based indicator comprising two fluorescent proteins and two Ca2+-responsive elements (a variant of calmodulin (CaM) and a CaM-binding peptide). This protocol details how to set up and conduct a Ca2+-imaging experiment, accomplish offline data processing (such as background correction) and convert the observed FRET ratio changes to Ca2+ concentrations. Additionally, we highlight some of the challenges in observing organellar Ca2+ and the alternative strategies researchers can employ for effectively calibrating the genetically encoded Ca2+ indicators in these locations. Setting up and conducting an initial calibration of the microscope system is estimated to take approximately 1 week, assuming that all the component parts are readily available. Cell culture and transfection is estimated to take approximately 3 d (from the time of plating cells on imaging dishes). An experiment and calibration will probably take a few hours. Finally, the offline data workup can take approximately 1 d depending on the extent of analysis.}, Author = {Palmer, Amy E and Tsien, Roger Y}, Date-Added = {2011-04-08 10:05:23 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Protoc}, Journal-Full = {Nature protocols}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Animals; Biological Markers; Calcium; Calmodulin; Calmodulin-Binding Proteins; Cells, Cultured; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Microscopy, Fluorescence}, Number = {3}, Pages = {1057-65}, pmid = {17406387}, Pst = {ppublish}, Title = {Measuring calcium signaling using genetically targetable fluorescent indicators}, Volume = {1}, Year = {2006}, url = {papers/Palmer_NatProtoc2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nprot.2006.172}} @article{Tour:2007, Abstract = {Intracellular Ca(2+) regulates numerous proteins and cellular functions and can vary substantially over submicron and submillisecond scales, so precisely localized fast detection is desirable. We have created a approximately 1-kDa biarsenical Ca(2+) indicator, called Calcium Green FlAsH (CaGF, 1), to probe [Ca(2+)] surrounding genetically targeted proteins. CaGF attached to a tetracysteine motif becomes ten-fold more fluorescent upon binding Ca(2+), with a K(d) of approximately 100 microM, <1-ms kinetics and good Mg(2+) rejection. In HeLa cells expressing tetracysteine-tagged connexin 43, CaGF labels gap junctions and reports Ca(2+) waves after injury. Total internal reflection microscopy of tetracysteine-tagged, CaGF-labeled alpha(1C) L-type calcium channels shows fast-rising depolarization-evoked Ca(2+) transients, whose lateral nonuniformity suggests that the probability of channel opening varies greatly over micron dimensions. With moderate Ca(2+) buffering, these transients decay surprisingly slowly, probably because most of the CaGF signal comes from closed channels feeling Ca(2+) from a tiny minority of clustered open channels. With high Ca(2+) buffering, CaGF signals decay as rapidly as the calcium currents, as expected for submicron Ca(2+) domains immediately surrounding active channels. Thus CaGF can report highly localized, rapid [Ca(2+)] dynamics.}, Author = {Tour, Oded and Adams, Stephen R and Kerr, Rex A and Meijer, Rene M and Sejnowski, Terrence J and Tsien, Richard W and Tsien, Roger Y}, Date-Added = {2011-04-08 10:05:15 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Chem Biol}, Journal-Full = {Nature chemical biology}, Keywords = {calcium sensor; calcium imaging; optical physiology; optical imaging; Fluorescence; Indicators and Reagents}, Mesh = {Calcium; Calcium Channels, L-Type; Calcium Signaling; Cell Line; Cells, Cultured; Connexin 43; Hela Cells; Humans; Kinetics; Luminescent Agents; Models, Biological; Organic Chemicals; Recombinant Proteins; Sensitivity and Specificity; Time Factors}, Month = {Jul}, Number = {7}, Pages = {423-31}, Pmc = {PMC2909385}, pmid = {17572670}, Pst = {ppublish}, Title = {Calcium Green FlAsH as a genetically targeted small-molecule calcium indicator}, Volume = {3}, Year = {2007}, url = {papers/Tour_NatChemBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nchembio.2007.4}} @article{Tsien:1988, Author = {Tsien, R Y}, Date-Added = {2011-04-07 18:45:36 -0400}, Date-Modified = {2011-04-07 18:45:36 -0400}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Mesh = {Animals; Calcium; Fluorescent Dyes; Microscopy, Fluorescence; Neurons; Photochemistry}, Month = {Oct}, Number = {10}, Pages = {419-24}, pmid = {2469158}, Pst = {ppublish}, Title = {Fluorescence measurement and photochemical manipulation of cytosolic free calcium}, Volume = {11}, Year = {1988}, url = {papers/Tsien_TrendsNeurosci1988.pdf}} @article{Grinvald:1986, Abstract = {Optical imaging of cortical activity offers several advantages over conventional electrophysiological and anatomical techniques. One can map a relatively large region, obtain successive maps to different stimuli in the same cortical area and follow variations in response over time. In the intact mammalian brain this imaging has been accomplished with the aid of voltage sensitive dyes. However, it has been known for many years that some intrinsic changes in the optical properties of the tissue are dependent on electrical or metabolic activity. Here we show that these changes can be used to study the functional architecture of cortex. Optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex, obtained by reflection measurements of the intrinsic signal, were confirmed with voltage sensitive dyes or by electrophysiological recordings. In addition, we describe an intrinsic signal originating from small arteries which can be used to investigate the communication between local neuronal activity and the microvasculature. One advantage of the method is that it is non-invasive and does not require dyes, a clear benefit for clinical applications.}, Author = {Grinvald, A and Lieke, E and Frostig, R D and Gilbert, C D and Wiesel, T N}, Date = {1986 Nov 27-Dec 3}, Date-Added = {2011-04-07 10:48:35 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; optical imaging; intrinsic signal; voltage sensor; sensory map; topographic map; visual system; visual cortex; rat; cat; Somatosensory Cortex}, Mesh = {Animals; Cats; Cerebral Cortex; Models, Neurological; Rats; Somatosensory Cortex; Vision, Ocular; Visual Perception}, Number = {6095}, Pages = {361-4}, pmid = {3785405}, Pst = {ppublish}, Title = {Functional architecture of cortex revealed by optical imaging of intrinsic signals}, Volume = {324}, Year = {1986}, url = {papers/Grinvald_Nature1986.pdf}, eprint = {http://dx.doi.org/10.1038/324361a0}} @article{Xu:2007a, Abstract = {Neuronal interactions between primary and secondary visual cortical areas are important for visual processing, but the spatiotemporal patterns of the interaction are not well understood. We used voltage-sensitive dye imaging to visualize neuronal activity in rat visual cortex and found visually evoked waves propagating from V1 to other visual areas. A primary wave originated in the monocular area of V1 and was "compressed" when propagating to V2. A reflected wave initiated after compression and propagated backward into V1. The compression occurred at the V1/V2 border, and local GABAA inhibition is important for the compression. The compression/reflection pattern provides a two-phase modulation: V1 is first depolarized by the primary wave, and then V1 and V2 are simultaneously depolarized by the reflected and primary waves, respectively. The compression/reflection pattern only occurred for evoked waves and not for spontaneous waves, suggesting that it is organized by an internal mechanism associated with visual processing.}, Author = {Xu, Weifeng and Huang, Xiaoying and Takagaki, Kentaroh and Wu, Jian-young}, Date-Added = {2011-04-06 19:04:24 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Spontaneous activity;visual cortex; visual system; Neocortex;Spontaneous activity;21 Neurophysiology;21 Cortical oscillations;optical imaging;optical physiology;voltage sensor;frontiers review}, Mesh = {Animals; Bicuculline; Data Interpretation, Statistical; Electrocardiography; Electrophysiology; Evoked Potentials, Visual; GABA Antagonists; Image Processing, Computer-Assisted; Immunohistochemistry; Photic Stimulation; Rats; Rats, Long-Evans; Somatosensory Cortex; Stereotyped Behavior; Visual Cortex}, Month = {Jul}, Number = {1}, Pages = {119-29}, Pmc = {PMC1988694}, pmid = {17610821}, Pst = {ppublish}, Title = {Compression and reflection of visually evoked cortical waves}, Volume = {55}, Year = {2007}, url = {papers/Xu_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.06.016}} @article{Benucci:2007, Abstract = {The visual cortex represents stimuli through the activity of neuronal populations. We measured the evolution of this activity in space and time by imaging voltage-sensitive dyes in cat area V1. Contrast-reversing stimuli elicit responses that oscillate at twice the stimulus frequency, indicating that signals originate mostly in complex cells. These responses stand clear of the noise, whose amplitude decreases as 1/frequency, and yield high-resolution maps of orientation preference and retinotopy. We first show how these maps are combined to yield the responses to focal, oriented stimuli. We then study the evolution of the oscillating activity in space and time. In the orientation domain, it is a standing wave. In the spatial domain, it is a traveling wave propagating at 0.2-0.5 m/s. These different dynamics indicate a fundamental distinction in the circuits underlying selectivity for position and orientation, two key stimulus attributes.}, Author = {Benucci, Andrea and Frazor, Robert A and Carandini, Matteo}, Date-Added = {2011-04-06 18:48:58 -0400}, Date-Modified = {2013-07-31 19:42:28 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Spontaneous activity; visual cortex; visual system; cat; sensory map; topographic map; voltage sensor; optical physiology; optical imaging; retinal wave paper; currOpinRvw}, Mesh = {Algorithms; Animals; Cats; Dendrites; Fluorescent Dyes; Fourier Analysis; Image Processing, Computer-Assisted; Nerve Net; Neurons; Photic Stimulation; Retina; Space Perception; Visual Cortex}, Month = {Jul}, Number = {1}, Pages = {103-17}, Pmc = {PMC2171365}, pmid = {17610820}, Pst = {ppublish}, Title = {Standing waves and traveling waves distinguish two circuits in visual cortex}, Volume = {55}, Year = {2007}, url = {papers/Benucci_Neuron2007.pdf}, Bdsk-File-2 = {papers/Benucci_Neuron2007a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.06.017}} @article{Ferezou:2006, Abstract = {Voltage-sensitive dye imaging resolves the spatiotemporal dynamics of supragranular subthreshold cortical activity with millisecond temporal resolution and subcolumnar spatial resolution. We used a flexible fiber optic image bundle to visualize voltage-sensitive dye dynamics in the barrel cortex of freely moving mice while simultaneously filming whisker-related behavior to generate two movies matched frame-by-frame with a temporal resolution of up to 2 ms. Sensory responses evoked by passive whisker stimulation lasted longer and spread further across the barrel cortex in awake mice compared to anesthetized mice. Passively evoked sensory responses were large during behaviorally quiet periods and small during active whisking. However, as an exploring mouse approached an object while whisking, large-amplitude, propagating cortical sensory activity was evoked by active whisker-touch. These experiments demonstrate that fiber optics can be used to image cortical sensory activity with high resolution in freely moving animals. The results demonstrate differential processing of sensory input depending upon behavior.}, Author = {Ferezou, Isabelle and Bolea, Sonia and Petersen, Carl C H}, Date-Added = {2011-04-06 18:37:46 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {voltage sensor; optical physiology; optical imaging; 21 Neurophysiology; 21 Cortical oscillations; Neocortex; Somatosensory Cortex; in vivo; Mouse; frontiers review}, Mesh = {Anesthesia, General; Animals; Behavior, Animal; Brain Mapping; Diagnostic Imaging; Evoked Potentials, Somatosensory; Fiber Optic Technology; Fluorescent Dyes; Image Processing, Computer-Assisted; Mice; Optical Fibers; Patch-Clamp Techniques; Somatosensory Cortex; Vibrissae; Wakefulness}, Month = {May}, Number = {4}, Pages = {617-29}, pmid = {16701211}, Pst = {ppublish}, Title = {Visualizing the cortical representation of whisker touch: voltage-sensitive dye imaging in freely moving mice}, Volume = {50}, Year = {2006}, url = {papers/Ferezou_Neuron2006.pdf}, Bdsk-File-2 = {papers/Ferezou_Neuron2006a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.03.043}} @article{Petersen:2003a, Abstract = {The rodent primary somatosensory cortex is spontaneously active in the form of locally synchronous membrane depolarizations (UP states) separated by quiescent hyperpolarized periods (DOWN states) both under anesthesia and during quiet wakefulness. In vivo whole-cell recordings and tetrode unit recordings were combined with voltage-sensitive dye imaging to analyze the relationship of the activity of individual pyramidal neurons in layer 2/3 to the ensemble spatiotemporal dynamics of the spontaneous depolarizations. These were either brief and localized to an area of a barrel column or occurred as propagating waves dependent on local glutamatergic synaptic transmission in layer 2/3. Spontaneous activity inhibited the sensory responses evoked by whisker deflection, accounting almost entirely for the large trial-to-trial variability of sensory-evoked postsynaptic potentials and action potentials. Subthreshold sensory synaptic responses evoked while a cortical area was spontaneously depolarized were smaller, briefer and spatially more confined. Surprisingly, whisker deflections evoked fewer action potentials during the spontaneous depolarizations despite neurons being closer to threshold. The ongoing spontaneous activity thus regulates the amplitude and the time-dependent spread of the sensory response in layer 2/3 barrel cortex.}, Author = {Petersen, Carl C H and Hahn, Thomas T G and Mehta, Mayank and Grinvald, Amiram and Sakmann, Bert}, Date-Added = {2011-04-06 18:35:34 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Spontaneous activity; Neocortex; in vivo; voltage sensor; optical imaging; optical physiology; 21 Neurophysiology; 21 Cortical oscillations; Somatosensory Cortex; rat}, Mesh = {Action Potentials; Anesthesia; Animals; Electrophysiology; Mice; Mice, Inbred C57BL; Neural Inhibition; Neurons; Pyramidal Cells; Rats; Rats, Wistar; Somatosensory Cortex; Synapses; Synaptic Transmission; Time Factors; Wakefulness}, Month = {Nov}, Number = {23}, Pages = {13638-43}, Pmc = {PMC263866}, pmid = {14595013}, Pst = {ppublish}, Title = {Interaction of sensory responses with spontaneous depolarization in layer 2/3 barrel cortex}, Volume = {100}, Year = {2003}, url = {papers/Petersen_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.2235811100}} @article{Burns:2007a, Abstract = {The standard method of detecting neurogenesis uses bromodeoxyuridine (BrdU) to label DNA synthesis followed by double labeling with neuronal markers. However, DNA synthesis may occur in events unrelated to neurogenesis including aneuploidy and abortive cell cycle reentry. Hence, it is important to confirm neurogenesis with methods other than BrdU incorporation. To this end, we have generated transgenic nestin-CreER mice that express tamoxifen-inducible Cre recombinase under the control of a nestin enhancer. When crossed with a ubiquitous Enhanced Green Fluorescent Protein (EGFP)-Cre-reporter line, the bitransgenic animals can reveal the nestin-positive progenitors and their progeny with EGFP after tamoxifen induction. This system has many applications including visualization of embryonic neural progenitors, detection of postnatally transformed radial glial cells, and labeling adult neural progenitors in the subventricular zone (SVZ). To examine the contribution of SVZ progenitors to cell replacement after stroke, tamoxifen-induced mice were challenged with focal ischemia or combined ischemia-hypoxia followed by BrdU injection. This analysis revealed only very few EGFP-positive cells outside the SVZ after focal ischemia but robust DNA synthesis by hippocampal neurons without immediate cell death following ischemia-hypoxia. These results suggest that the nestin-CreER system is a useful tool for detecting embryonic and adult neurogensis. They also confirm the existence of nonproliferative DNA synthesis by old neurons after experimental brain injury.}, Author = {Burns, Kevin A and Ayoub, Albert E and Breunig, Joshua J and Adhami, Faisal and Weng, Wei-Lan and Colbert, Melissa C and Rakic, Pasko and Kuan, Chia-Yi}, Date-Added = {2011-04-06 18:33:09 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Cereb Cortex}, Journal-Full = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {01 Adult neurogenesis general}, Mesh = {Animals; Apoptosis; DNA; Hypoxia-Ischemia, Brain; Intermediate Filament Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Receptors, Estrogen}, Month = {Nov}, Number = {11}, Pages = {2585-92}, pmid = {17259645}, Pst = {ppublish}, Title = {Nestin-CreER mice reveal DNA synthesis by nonapoptotic neurons following cerebral ischemia hypoxia}, Volume = {17}, Year = {2007}, url = {papers/Burns_CerebCortex2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhl164}} @article{Luczak:2007a, Abstract = {Even in the absence of sensory stimulation, the neocortex shows complex spontaneous activity patterns, often consisting of alternating "DOWN" states of generalized neural silence and "UP" states of massive, persistent network activity. To investigate how this spontaneous activity propagates through neuronal assemblies in vivo, we simultaneously recorded populations of 50-200 cortical neurons in layer V of anesthetized and awake rats. Each neuron displayed a virtually unique spike pattern during UP states, with diversity seen amongst both putative pyramidal cells and interneurons, reflecting a complex but stereotypically organized sequential spread of activation through local cortical networks. Spike timing was most precise during the first approximately 100 ms after UP state onset, and decayed as UP states progressed. A subset of UP states propagated as traveling waves, but waves passing a given point in either direction initiated similar local sequences, suggesting local networks as the substrate of sequential firing patterns. A search for repeating motifs indicated that their occurrence and structure was predictable from neurons' individual latencies to UP state onset. We suggest that these stereotyped patterns arise from the interplay of intrinsic cellular conductances and local circuit properties.}, Author = {Luczak, Artur and Barth{\'o}, Peter and Marguet, Stephan L and Buzs{\'a}ki, Gy{\"o}rgy and Harris, Kenneth D}, Date-Added = {2011-04-06 18:28:22 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {voltage sensor; optical imaging; optical physiology; Spontaneous activity; 21 Cortical oscillations; 21 Neurophysiology; extracellular}, Mesh = {Animals; Neocortex; Rats; Rats, Sprague-Dawley; Reaction Time}, Month = {Jan}, Number = {1}, Pages = {347-52}, Pmc = {PMC1765463}, pmid = {17185420}, Pst = {ppublish}, Title = {Sequential structure of neocortical spontaneous activity in vivo}, Volume = {104}, Year = {2007}, url = {papers/Luczak_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0605643104}} @article{Weliky:2000, Author = {Weliky, M}, Date-Added = {2011-04-06 18:26:34 -0400}, Date-Modified = {2011-04-06 18:27:53 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {retinal wave paper; Spontaneous activity; 21 Activity-development; development; visual system; visual cortex; 21 Cortical oscillations; review}, Mesh = {Animals; Cats; Ferrets; Geniculate Bodies; Neurons; Retina; Synapses; Visual Cortex; Visual Pathways}, Month = {Sep}, Number = {3}, Pages = {427-30}, pmid = {11055425}, Pst = {ppublish}, Title = {Correlated neuronal activity and visual cortical development}, Volume = {27}, Year = {2000}, url = {papers/Weliky_Neuron2000.pdf}} @article{Djurisic:2004, Abstract = {To obtain a more complete description of individual neurons, it is necessary to complement the electrical patch pipette measurements with technologies that permit a massive parallel recording from many sites on neuronal processes. This can be achieved by using voltage imaging with intracellular dyes. With this approach, we investigated the functional structure of a mitral cell, the principal output neuron in the rat olfactory bulb. The most significant finding concerns the characteristics of EPSPs at the synaptic sites and surprisingly small attenuation along the trunk of the primary dendrite. Also, the experiments were performed to determine the number, location, and stability of spike trigger zones, the excitability of terminal dendritic branches, and the pattern and nature of spike initiation and propagation in the primary and secondary dendrites. The results show that optical data can be used to deduce the amplitude and shape of the EPSPs evoked by olfactory nerve stimulation at the site of origin (glomerular tuft) and to determine its attenuation along the entire length of the primary dendrite. This attenuation corresponds to an unusually large mean apparent "length constant" of the primary dendrite. Furthermore, the images of spike trigger zones showed that an action potential can be initiated in three different compartments of the mitral cell: the soma-axon region, the primary dendrite trunk, and the terminal dendritic tuft, which appears to be fully excitable. Finally, secondary dendrites clearly support the active propagation of action potentials.}, Author = {Djurisic, Maja and Antic, Srdjan and Chen, Wei R and Zecevic, Dejan}, Date-Added = {2011-04-06 17:53:49 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Mesh = {Action Potentials; Animals; Coloring Agents; Dendrites; Electric Stimulation; Excitatory Postsynaptic Potentials; Feedback, Physiological; Microelectrodes; Microscopy, Video; Neurons; Olfactory Bulb; Patch-Clamp Techniques; Photobleaching; Rats; Rats, Sprague-Dawley; Styrenes; Synaptic Transmission}, Month = {Jul}, Number = {30}, Pages = {6703-14}, pmid = {15282273}, Pst = {ppublish}, Title = {Voltage imaging from dendrites of mitral cells: EPSP attenuation and spike trigger zones}, Volume = {24}, Year = {2004}, url = {papers/Djurisic_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0307-04.2004}} @article{Sutor:1994, Abstract = {1. Adult rats and rats with a postnatal age of 3-29 days (PN 3-29) were used for the preparation of in vitro slices of the frontal neocortex. Epileptiform activity was induced by bath application of the gamma-aminobutyric acid-A (GABAA) receptor antagonists bicuculline or picrotoxin. 2. The voltage-sensitive dye RH 414 and a laser scanning microscope were used for multiple-site optical recordings of membrane potential changes associated with epileptiform activity. Optical signals were compared with simultaneously measured extra-cellular field potentials. 3. Optical signals could be reliably recorded for the duration of the experiments (2-4 h). Extracellular recordings of convulsant-induced paroxysmal depolarizing shifts (PDSs) in slices stained with RH 414 were comparable with those obtained in unstained slices. Changes in dye signals in response to reductions in extracellular calcium, addition of tetrodotoxin (TTX), or application of excitatory amino acid receptor antagonists indicate that the fluorescence changes correlate well with established electrophysiological measures of epileptiform activity. 4. In slices from adult animals, dye signals were observed at all recording sites. The response with the shortest latency occurred invariably at the site of stimulation, and activity spread rapidly in both vertical and horizontal directions. Spread was significantly faster in the vertical than in the horizontal direction. 5. Epileptiform activity was absent or only weakly expressed in slices from PN 3-9 animals. Activity was detectable predominantly in upper cortical layers. 6. Dye signals were observed at all measurement points in slices from PN 10-19 animals. In this age group, peak amplitude increased with spread of activity from lower to upper cortical layers. There was no significant difference between the speed of propagation in the vertical and in the horizontal directions. Spontaneous epileptiform activity occurred at a high rate in the PN 10-19 age group, and signals associated with spontaneous epileptiform events were largest in upper layers. 7. In the PN 10-19 age group, optical signals were characterized by the repetitive occurrence of PDS discharges superimposed on a sustained response. The amplitude of the sustained response decreased with increasing distance from the site of stimulation. Analysis of the latencies revealed that the superimposed PDS-like events were generated at multiple sites within the scanning area. Amplitude and rate of rise were largest in slices from PN 10-19 animals. These values declined with ongoing development.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Sutor, B and Hablitz, J J and Rucker, F and ten Bruggencate, G}, Date-Added = {2011-04-06 17:39:29 -0400}, Date-Modified = {2011-04-06 17:42:31 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {voltage sensor; optical physiology; optical imaging; 21 Neurophysiology; Neocortex; rat; in vitro; development; Epilepsy; Seizures; frontiers review}, Mesh = {Age Factors; Animals; Bicuculline; Culture Techniques; Epilepsy; Frontal Lobe; Membrane Potentials; Microscopy; Picrotoxin; Rats; Rats, Wistar; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission}, Month = {Oct}, Number = {4}, Pages = {1756-68}, pmid = {7823100}, Pst = {ppublish}, Title = {Spread of epileptiform activity in the immature rat neocortex studied with voltage-sensitive dyes and laser scanning microscopy}, Volume = {72}, Year = {1994}, url = {papers/Sutor_JNeurophysiol1994.pdf}} @article{Shoham:1999, Abstract = {Conventional imaging techniques have provided high-resolution imaging either in the spatial domain or in the temporal domain. Optical imaging utilizing voltage-sensitive dyes has long had the unrealized potential to achieve high resolution in both domains simultaneously, providing subcolumnar spatial detail with millisecond precision. Here, we present a series of developments in voltage-sensitive dyes and instrumentation that make functional imaging of cortical dynamics practical, in both anesthetized and awake behaving preparations, greatly facilitating exploration of the cortex. We illustrate this advance by analyzing the millisecond-by-millisecond emergence of orientation maps in cat visual cortex.}, Author = {Shoham, D and Glaser, D E and Arieli, A and Kenet, T and Wijnbergen, C and Toledo, Y and Hildesheim, R and Grinvald, A}, Date-Added = {2011-04-06 17:14:31 -0400}, Date-Modified = {2011-04-06 17:25:17 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {intrinsic signal; Optics; optical physiology; optical imaging; cat; Neocortex; in vivo; voltage sensor; visual system; visual cortex; function; sensory map; topographic map}, Mesh = {Animals; Brain Mapping; Cats; Cerebral Cortex; Coloring Agents; Electrophysiology; Haplorhini; Heart Rate; Image Processing, Computer-Assisted; Orientation; Photic Stimulation; Rats}, Month = {Dec}, Number = {4}, Pages = {791-802}, pmid = {10624943}, Pst = {ppublish}, Title = {Imaging cortical dynamics at high spatial and temporal resolution with novel blue voltage-sensitive dyes}, Volume = {24}, Year = {1999}, url = {papers/Shoham_Neuron1999.pdf}} @article{Friedrich:2004, Abstract = {In the olfactory bulb (OB) of zebrafish and other species, odors evoke fast oscillatory population activity and specific firing rate patterns across mitral cells (MCs). This activity evolves over a few hundred milliseconds from the onset of the odor stimulus. Action potentials of odor-specific MC subsets phase-lock to the oscillation, defining small and distributed ensembles within the MC population output. We found that oscillatory field potentials in the zebrafish OB propagate across the OB in waves. Phase-locked MC action potentials, however, were synchronized without a time lag. Firing rate patterns across MCs analyzed with low temporal resolution were informative about odor identity. When the sensitivity for phase-locked spiking was increased, activity patterns became progressively more informative about odor category. Hence, information about complementary stimulus features is conveyed simultaneously by the same population of neurons and can be retrieved selectively by biologically plausible mechanisms, indicating that seemingly alternative coding strategies operating on different time scales may coexist.}, Author = {Friedrich, Rainer W and Habermann, Christopher J and Laurent, Gilles}, Date-Added = {2011-04-06 14:44:20 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {voltage sensor; Olfactory Bulb; Zebrafish; function; sensory map; topographic map; network; synchrony; oscillations; optical imaging; optical physiology}, Mesh = {Action Potentials; Animals; Brain Mapping; Cortical Synchronization; Neurons; Nose; Olfactory Bulb; Patch-Clamp Techniques; Zebrafish}, Month = {Aug}, Number = {8}, Pages = {862-71}, pmid = {15273692}, Pst = {ppublish}, Title = {Multiplexing using synchrony in the zebrafish olfactory bulb}, Volume = {7}, Year = {2004}, url = {papers/Friedrich_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1292}} @article{Friedrich:1998, Abstract = {Odor information is first represented in the brain by patterns of input activity across the glomeruli of the olfactory bulb (OB). To examine how odorants are represented at this stage of olfactory processing, we labeled anterogradely the axons of olfactory receptor neurons with the voltage-sensitive dye Di8-ANEPPQ in zebrafish. The activity induced by diverse natural odorants in afferent axons and across the array of glomeruli was then recorded optically. The results show that certain subregions of the OB are preferentially activated by defined chemical odorant classes. Within these subregions, "ordinary" odorants (amino acids, bile acids, and nucleotides) induce overlapping activity patterns involving multiple glomeruli, indicating that they are represented by combinatorial activity patterns. In contrast, two putative pheromone components (prostaglandin F2alpha and 17alpha, 20beta-dihydroxy-4-pregnene-3-one-20-sulfate) each induce a single focus of activity, at least one of which comes from a single, highly specific and sensitive glomerulus. These results indicate that the OB is organized into functional subregions processing classes of odorants. Furthermore, they suggest that individual odorants can be represented by "combinatorial" or "noncombinatorial" (focal) activity patterns and that the latter may serve to process odorants triggering distinct responses such as that of pheromones.}, Author = {Friedrich, R W and Korsching, S I}, Date-Added = {2011-04-06 14:32:49 -0400}, Date-Modified = {2011-04-06 14:38:02 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {voltage sensor; Olfactory Bulb; Zebrafish; Technique; optical physiology; optical imaging; axons; tracer; sensory map; topographic map; frontiers review}, Mesh = {Animals; Axons; Bile Acids and Salts; Electric Stimulation; Fluorescent Dyes; Image Processing, Computer-Assisted; Microscopy, Fluorescence; Nucleotides; Odors; Olfactory Bulb; Olfactory Receptor Neurons; Pheromones; Pyridinium Compounds; Zebrafish}, Month = {Dec}, Number = {23}, Pages = {9977-88}, pmid = {9822753}, Pst = {ppublish}, Title = {Chemotopic, combinatorial, and noncombinatorial odorant representations in the olfactory bulb revealed using a voltage-sensitive axon tracer}, Volume = {18}, Year = {1998}, url = {papers/Friedrich_JNeurosci1998.pdf}} @article{Niessing:2010, Abstract = {The categorial nature of sensory, cognitive and behavioural acts indicates that the brain classifies neuronal activity patterns into discrete representations. Pattern classification may be achieved by abrupt switching between discrete activity states of neuronal circuits, but few experimental studies have directly tested this. We gradually varied the concentration or molecular identity of odours and optically measured responses across output neurons of the olfactory bulb in zebrafish. Whereas population activity patterns were largely insensitive to changes in odour concentration, morphing of one odour into another resulted in abrupt transitions between odour representations. These transitions were mediated by coordinated response changes among small neuronal ensembles rather than by shifts in the global network state. The olfactory bulb therefore classifies odour-evoked input patterns into many discrete and defined output patterns, as proposed by attractor models. This computation is consistent with perceptual phenomena and may represent a general information processing strategy in the brain.}, Author = {Niessing, J{\"o}rn and Friedrich, Rainer W}, Date-Added = {2011-04-06 13:32:38 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Zebrafish; Olfactory Bulb; optical physiology; optical imaging; Neurophysiology; function; sensory map; topographic map; network; Computational Biology}, Mesh = {Animals; Nerve Net; Odors; Olfactory Bulb; Sensation; Zebrafish}, Month = {May}, Number = {7294}, Pages = {47-52}, pmid = {20393466}, Pst = {ppublish}, Title = {Olfactory pattern classification by discrete neuronal network states}, Volume = {465}, Year = {2010}, url = {papers/Niessing_Nature2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08961}} @article{Niell:2004a, Abstract = {Although development of the nervous system is inherently a process of dynamic change, until recently it has generally been investigated by inference from static images. However, advances in live optical imaging are now allowing direct observation of growth, synapse formation, and even incipient function in the developing nervous system, at length scales from molecules to cortical regions, and over timescales from milliseconds to months. In this review, we provide technical background and present examples of how these new methods, including confocal and two-photon microscopy, GFP-based markers, and functional indicators, are being applied to provide fresh insight into long-standing questions of neural development.}, Author = {Niell, Cristopher M and Smith, Stephen J}, Date-Added = {2011-04-06 12:51:06 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Annu Rev Physiol}, Journal-Full = {Annual review of physiology}, Keywords = {review; optical imaging; structural remodeling; 21 Activity-development; calcium imaging; optical physiology; microscopy;}, Mesh = {Animals; Axons; Brain Mapping; Cell Division; Cell Movement; Diagnostic Imaging; Humans; Nervous System; Nervous System Physiological Phenomena; Neural Pathways; Optics and Photonics; Synapses}, Pages = {771-98}, pmid = {14977421}, Pst = {ppublish}, Title = {Live optical imaging of nervous system development}, Volume = {66}, Year = {2004}, url = {papers/Niell_AnnuRevPhysiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.physiol.66.082602.095217}} @article{Friedrich:1997, Abstract = {Odors are thought to be represented by a distributed code across the glomerular modules in the olfactory bulb (OB). Here, we optically imaged presynaptic activity in glomerular modules of the zebrafish OB induced by a class of natural odorants (amino acids [AAs]) after labeling of primary afferents with a calcium-sensitive dye. AAs induce complex combinatorial patterns of active glomerular modules that are unique for different stimuli and concentrations. Quantitative analysis shows that defined molecular features of stimuli are correlated with activity in spatially confined groups of glomerular modules. These results provide direct evidence that identity and concentration of odorants are encoded by glomerular activity patterns and reveal a coarse chemotopic organization of the array of glomerular modules.}, Author = {Friedrich, R W and Korsching, S I}, Date-Added = {2011-04-06 11:51:21 -0400}, Date-Modified = {2011-04-06 11:53:00 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Zebrafish; Olfactory Bulb; voltage sensor; optical physiology; optical imaging; frontiers review; function; Sensory/physiology; topographic map; sensory map}, Mesh = {Amino Acids; Animals; Calcium; Denervation; Dose-Response Relationship, Drug; Image Processing, Computer-Assisted; Multivariate Analysis; Nerve Regeneration; Olfactory Bulb; Olfactory Nerve; Olfactory Receptor Neurons; Presynaptic Terminals; Receptors, Odorant; Smell; Zebrafish}, Month = {May}, Number = {5}, Pages = {737-52}, pmid = {9182799}, Pst = {ppublish}, Title = {Combinatorial and chemotopic odorant coding in the zebrafish olfactory bulb visualized by optical imaging}, Volume = {18}, Year = {1997}, url = {papers/Friedrich_Neuron1997.pdf}} @article{Kauer:1988, Abstract = {The encoding of olfactory information in the central nervous system (CNS) depends on spatially distributed patterns of activity generated simultaneously in many neuronal circuits. Optical neurophysiological recording permits analysis of neural activity non-invasively and with high spatial and temporal resolution. Here, a video method for imaging voltage-sensitive dye fluorescence in vivo is used to map neuronal activity in local circuits of the salamander olfactory bulb. The method permits the imaging of simultaneous ensemble transmembrane activity in real time. After electrical stimulation of the olfactory nerve, activity spreads centripetally from the sites of synaptic input to generate nonhomogeneous response patterns that are presumably mediated by local circuits within the bulbar layers. The results also show the overlapping temporal sequences of activation of cell groups in each layer. The method thus provides high resolution, sequential video images of the spatial and temporal progression of transmembrane events in neuronal circuits after afferent stimulation and offers the opportunity for studying ensemble events in other brain regions.}, Author = {Kauer, J S}, Date-Added = {2011-04-06 11:39:21 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; optical imaging; voltage sensor; Salamandridae; Olfactory Bulb; frontiers review}, Mesh = {Animals; Electric Stimulation; Fluorescence; Fluorescent Dyes; Neurophysiology; Olfactory Bulb; Pyridinium Compounds; Television; Urodela}, Month = {Jan}, Number = {6152}, Pages = {166-8}, pmid = {3340163}, Pst = {ppublish}, Title = {Real-time imaging of evoked activity in local circuits of the salamander olfactory bulb}, Volume = {331}, Year = {1988}, url = {papers/Kauer_Nature1988.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/331166a0}} @article{Rubin:1999, Abstract = {We adapted the technique of intrinsic signal imaging to visualize how odorant concentration and structure are represented spatially in the rat olfactory bulb. Most odorants activated one or more glomeruli in the imaged region of the bulb; these optically imaged responses reflected the excitation of underlying neurons. Odorant-evoked patterns were similar across animals and symmetrical in the two bulbs of the same animal. The variable sensitivity of individual glomeruli produced distinct maps for different odorant concentrations. Using a series of homologous aldehydes, we found that glomeruli were tuned to detect particular molecular features and that maps of similar molecules were highly correlated. These characteristics suggest that odorants and their concentrations can be encoded by distinct spatial patterns of glomerular activation.}, Author = {Rubin, B D and Katz, L C}, Date-Added = {2011-04-06 11:18:37 -0400}, Date-Modified = {2011-04-06 11:20:03 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology; optical imaging; intrinsic signal; Olfactory Bulb; rat; in vivo; function; topographic map}, Mesh = {Animals; Arachis hypogaea; Brain Mapping; Electrophysiology; Female; Mammals; Microscopy, Video; Odors; Olfactory Bulb; Olfactory Receptor Neurons; Pentanols; Rats; Rats, Long-Evans; Smell; Stimulation, Chemical}, Month = {Jul}, Number = {3}, Pages = {499-511}, pmid = {10433262}, Pst = {ppublish}, Title = {Optical imaging of odorant representations in the mammalian olfactory bulb}, Volume = {23}, Year = {1999}, url = {papers/Rubin_Neuron1999.pdf}} @article{Kandler:1995, Abstract = {Sensitive new tracers and imaging techniques have revealed that gap junction coupling during brain development is much more pronounced than previously believed. Recent results demonstrate that cell coupling can produce functional neuron assemblies characterized by synchronized fluctuations in the cytosolic Ca2+ concentration. Coupling is especially pronounced before and during the period of synapse formation and initial establishment of neuronal circuits. Thus, communication via gap junctions may generate coordinated electrical or biochemical activity before the onset of synaptic transmission, and thereby provide the outlines of functional architecture in the developing brain.}, Author = {Kandler, K and Katz, L C}, Date-Added = {2011-04-06 11:14:10 -0400}, Date-Modified = {2011-04-06 11:15:41 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Gap Junctions; electrical coupling; development; Neocortex; review; synapse formation; 21 Activity-development; Cooperative Behavior; Competitive Behavior}, Mesh = {Animals; Brain; Cerebral Cortex; Gap Junctions; Models, Neurological; Retina; Spinal Cord; Synaptic Transmission}, Month = {Feb}, Number = {1}, Pages = {98-105}, pmid = {7773012}, Pst = {ppublish}, Title = {Neuronal coupling and uncoupling in the developing nervous system}, Volume = {5}, Year = {1995}, url = {papers/Kandler_CurrOpinNeurobiol1995.pdf}} @article{Orbach:1983, Abstract = {We have investigated the use of voltage-sensitive dyes to monitor neuronal activity in the intact salamander olfactory bulb. After a 10- to 20-min staining period, a magnified image of an in vitro or an in vivo preparation was formed on a 124-element photodiode array. The array was used to simultaneously record absorption or fluorescence changes from 124 adjacent areas of the bulb. At the magnifications used, each detector received light from 100 to 1000 neurons. Relatively large absorption and fluorescence signals were found in response to olfactory nerve stimulation; all of the results presented were from single trials. Because of the large signal size, measurements on in vivo preparations using epi-illumination also had good signal-to-noise ratios. There were significant differences in signal time course between adjacent detectors which suggested a spatial resolution on the order of 200 microns. Tentative assignments of the cellular origins of some signals could be made from the results of paired volley experiments. The results suggest that optical monitoring of membrane potential could provide a useful method for studying neuronal organization in the intact vertebrate central nervous system.}, Author = {Orbach, H S and Cohen, L B}, Date-Added = {2011-04-06 11:05:00 -0400}, Date-Modified = {2011-04-06 11:06:58 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {voltage sensor; optical physiology; optical imaging; in vivo; Olfactory Bulb; Salamandridae; frontiers review}, Mesh = {Ambystoma; Animals; Central Nervous System; Coloring Agents; Monitoring, Physiologic; Olfactory Bulb; Synapses; Vertebrates}, Month = {Nov}, Number = {11}, Pages = {2251-62}, pmid = {6631479}, Pst = {ppublish}, Title = {Optical monitoring of activity from many areas of the in vitro and in vivo salamander olfactory bulb: a new method for studying functional organization in the vertebrate central nervous system}, Volume = {3}, Year = {1983}, url = {papers/Orbach_JNeurosci1983.pdf}} @article{Meister:2001, Abstract = {The sense of smell originates in a diverse array of receptor neurons, comprising up to 1000 different types. To understand how these parallel channels encode chemical stimuli, we recorded the responses of glomeruli in the olfactory bulbs of the anesthetized rat, by optical imaging of intrinsic signals. Odor stimulation produced two kinds of optical responses at the surface of the bulb: a broad diffuse component superposed by discrete small spots. Histology showed that the spots correspond to individual glomeruli, and that approximately 400 of them can be monitored in this way. Based on its wavelength-dependence, this optical signal appears to derive from changes in light scattering during neural activity. Pure odorants generally activated several glomeruli in a bilaterally symmetric pattern, whose extent varied greatly with concentration. A simple formalism for ligand binding accounts quantitatively for this concentration dependence and yields the effective affinity with which a glomerulus responds to an odorant. When tested with aliphatic molecules of increasing carbon chain length, many glomeruli were sharply tuned for one or two adjacent chain lengths. Glomeruli with similar tuning properties were located near each other, producing a systematic map of molecular chain length on the surface of the olfactory bulb. Given local inhibitory circuits within the olfactory bulb, this can account for the observed functional inhibition between related odors. We explore several parallels to the function and architecture of the visual system that help interpret the neural representation of odors.}, Author = {Meister, M and Bonhoeffer, T}, Date-Added = {2011-04-06 10:55:30 -0400}, Date-Modified = {2011-04-06 10:56:36 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {intrinsic signal; Olfactory Bulb; in vivo; rat; topographic map; function; Imaging; optical imaging; optical physiology}, Mesh = {Administration, Inhalation; Aldehydes; Animals; Brain Mapping; Dose-Response Relationship, Drug; Electron Transport Complex IV; Female; Hemoglobins; Image Processing, Computer-Assisted; Light; Odors; Olfactory Bulb; Oxygen Consumption; Rats; Rats, Wistar; Receptors, Odorant; Smell; Stimulation, Chemical; Structure-Activity Relationship}, Month = {Feb}, Number = {4}, Pages = {1351-60}, pmid = {11160406}, Pst = {ppublish}, Title = {Tuning and topography in an odor map on the rat olfactory bulb}, Volume = {21}, Year = {2001}, url = {papers/Meister_JNeurosci2001.pdf}} @article{Denk:1990, Abstract = {Molecular excitation by the simultaneous absorption of two photons provides intrinsic three-dimensional resolution in laser scanning fluorescence microscopy. The excitation of fluorophores having single-photon absorption in the ultraviolet with a stream of strongly focused subpicosecond pulses of red laser light has made possible fluorescence images of living cells and other microscopic objects. The fluorescence emission increased quadratically with the excitation intensity so that fluorescence and photo-bleaching were confined to the vicinity of the focal plane as expected for cooperative two-photon excitation. This technique also provides unprecedented capabilities for three-dimensional, spatially resolved photochemistry, particularly photolytic release of caged effector molecules.}, Author = {Denk, W and Strickler, J H and Webb, W W}, Date-Added = {2011-04-06 10:40:23 -0400}, Date-Modified = {2011-04-06 10:46:38 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {multiphoton; microscopy; Optics; Lasers; Imaging; Technique; Classical/physiology; optical physiology}, Mesh = {Animals; Cell Line; Chromosomes; Fluorescent Dyes; Kidney; Lasers; Microscopy, Fluorescence; Photochemistry; Radiation; Swine; Ultraviolet Rays}, Month = {Apr}, Number = {4951}, Pages = {73-6}, pmid = {2321027}, Pst = {ppublish}, Title = {Two-photon laser scanning fluorescence microscopy}, Volume = {248}, Year = {1990}} @article{Gross:1986, Abstract = {We report the first imaging of the spatial distributions of transmembrane potential changes induced in nonexcitable cells by applied external electric fields. These changes are indicated by the fluorescence intensity of a charge-shift potentiometric dye incorporated in the cell plasma membrane and measured by digital intensified video microscopy.}, Author = {Gross, D and Loew, L M and Webb, W W}, Date-Added = {2011-04-06 10:38:16 -0400}, Date-Modified = {2011-04-06 10:39:53 -0400}, Journal = {Biophys J}, Journal-Full = {Biophysical journal}, Keywords = {Optics; optical physiology; optical imaging; microscopy; voltage sensor}, Mesh = {Basidiomycota; Carcinoma, Squamous Cell; Cell Line; Cell Membrane; Electrophysiology; Fluorescent Dyes; Humans; Membrane Potentials; Plant Physiological Phenomena; Protoplasts; Pyridinium Compounds; Secale cereale}, Month = {Aug}, Number = {2}, Pages = {339-48}, Pmc = {PMC1329750}, pmid = {3741986}, Pst = {ppublish}, Title = {Optical imaging of cell membrane potential changes induced by applied electric fields}, Volume = {50}, Year = {1986}, url = {papers/Gross_BiophysJ1986.pdf}} @article{Hill:1950, Author = {Hill, D K}, Date-Added = {2011-04-05 17:14:26 -0400}, Date-Modified = {2016-01-13 18:15:19 +0000}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {NERVES; optical physiology; imaging; intrinsic signal; optics; Technique; optical imaging; Classical/physiology}, Month = {Oct}, Number = {3-4}, Pages = {304-27}, Pmc = {PMC1392827}, pmid = {14795441}, Pst = {ppublish}, Title = {The volume change resulting from stimulation of a giant nerve fibre}, Volume = {111}, Year = {1950}, url = {papers/HILL_JPhysiol1950.pdf}} @article{Kaas:1990, Abstract = {The organization of the visual cortex has been considered to be highly stable in adult mammals. However, 5 degrees to 10 degrees lesions of the retina in the contralateral eye markedly altered the systematic representations of the retina in primary and secondary visual cortex when matched inputs from the ipsilateral eye were also removed. Cortical neurons that normally have receptive fields in the lesioned region of the retina acquired new receptive fields in portions of the retina surrounding the lesions. The capacity for such changes may be important for normal adjustments of sensory systems to environmental contingencies and for recoveries from brain damage.}, Author = {Kaas, J H and Krubitzer, L A and Chino, Y M and Langston, A L and Polley, E H and Blair, N}, Date-Added = {2011-04-05 16:18:09 -0400}, Date-Modified = {2011-04-05 16:20:14 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; visual system; visual cortex; retina; topographic map; Sensory Deprivation; activity manipulation; function}, Mesh = {Afferent Pathways; Animals; Cats; Functional Laterality; Neurons; Photic Stimulation; Retina; Somatosensory Cortex; Visual Cortex}, Month = {Apr}, Number = {4952}, Pages = {229-31}, pmid = {2326637}, Pst = {ppublish}, Title = {Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina}, Volume = {248}, Year = {1990}} @article{Baseler:2011, Abstract = {The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively.}, Author = {Baseler, Heidi A and Gouws, Andr{\'e} and Haak, Koen V and Racey, Christopher and Crossland, Michael D and Tufail, Adnan and Rubin, Gary S and Cornelissen, Frans W and Morland, Antony B}, Date-Added = {2011-04-05 12:54:56 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {visual cortex; fmri; visual system; retina; function; topographic map; Sensory Deprivation; neurological disorder; human; 21 Activity-development; structural remodeling}, Month = {Mar}, pmid = {21441924}, Pst = {aheadofprint}, Title = {Large-scale remapping of visual cortex is absent in adult humans with macular degeneration}, Year = {2011}, url = {papers/Baseler_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2793}} @article{Salzberg:1983, Abstract = {Optical methods are shown to monitor action potentials from a population of nerve terminals in the neurohypophysis of Xenopus. Calcium antagonists such as cadmium and nickel ions block a component of the action potential that probably reflects a calcium-mediated potassium conductance, and tetrodotoxin blocks an inward sodium current, revealing a calcium component to the action potential upstroke.}, Author = {Salzberg, B M and Obaid, A L and Senseman, D M and Gainer, H}, Date = {1983 Nov 3-9}, Date-Added = {2011-04-05 12:29:37 -0400}, Date-Modified = {2011-04-05 12:29:37 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Mesh = {Action Potentials; Animals; Cadmium; Calcium; Hypothalamus; Nickel; Pituitary Gland, Posterior; Sodium; Tetrodotoxin; Xenopus laevis}, Number = {5938}, Pages = {36-40}, pmid = {6633657}, Pst = {ppublish}, Title = {Optical recording of action potentials from vertebrate nerve terminals using potentiometric probes provides evidence for sodium and calcium components}, Volume = {306}, Year = {1983}, url = {papers/Salzberg_Nature1983.pdf}} @article{Tsodyks:1999, Abstract = {The relation between the activity of a single neocortical neuron and the dynamics of the network in which it is embedded was explored by single-unit recordings and real-time optical imaging. The firing rate of a spontaneously active single neuron strongly depends on the instantaneous spatial pattern of ongoing population activity in a large cortical area. Very similar spatial patterns of population activity were observed both when the neuron fired spontaneously and when it was driven by its optimal stimulus. The evoked patterns could be used to reconstruct the spontaneous activity of single neurons.}, Author = {Tsodyks, M and Kenet, T and Grinvald, A and Arieli, A}, Date-Added = {2011-04-05 12:28:35 -0400}, Date-Modified = {2011-04-05 12:28:46 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {optical physiology; imaging; intrinsic signal; optics; voltage sensor; optical imaging; microscopy}, Mesh = {Action Potentials; Animals; Brain Mapping; Cats; Evoked Potentials, Visual; Image Processing, Computer-Assisted; Nerve Net; Neurons; Patch-Clamp Techniques; Photic Stimulation; Visual Cortex; Visual Pathways}, Month = {Dec}, Number = {5446}, Pages = {1943-6}, pmid = {10583955}, Pst = {ppublish}, Title = {Linking spontaneous activity of single cortical neurons and the underlying functional architecture}, Volume = {286}, Year = {1999}, url = {papers/Tsodyks_Science1999.pdf}} @article{Arieli:1995, Abstract = {1. We examined the spatiotemporal organization of ongoing activity in cat visual areas 17 and 18, in relation to the spontaneous activity of individual neurons. To search for coherent activity, voltage-sensitive dye signals were correlated with the activity of single neurons by the use of spike-triggered averaging. In each recording session an area of at least 2 x 2 mm of cortex was imaged, with 124 diodes. In addition, electrical recordings from two isolated units, the local field potential (LFP) from the same microelectrodes, and the surface electroencephalogram (EEG) were recorded simultaneously. 2. The optical signals recorded from the dye were similar to the LFP recorded from the same site. Optical signals recorded from different cortical sites exhibited a different time course. Therefore real-time optical imaging provides information that is equivalent in many ways to multiple-site LFP recordings. 3. The spontaneous firing of single neurons was highly correlated with the optical signals and with the LFP. In 88\% of the neurons recorded during spontaneous activity, a significant correlation was found between the occurrence of a spike and the optical signal recorded in a large cortical region surrounding the recording site. This result indicates that spontaneous activity of single neurons is not an independent process but is time locked to the firing or to the synaptic inputs from numerous neurons, all activated in a coherent fashion even without a sensory input. 4. For the cases showing correlation with the optical signal, 27-36\% of the optical signal during spike occurrence was directly related to the occurrence of spontaneous spikes in a single neuron, over an area of 2 x 2 mm. In the same cortical area, 43-55\% of the activity was directly related to the visual stimulus. 5. Surprisingly, we found that the amplitude of this coherent ongoing activity, recorded optically, was often almost as large as the activity evoked by optimal visual stimulation. The amplitude of the ongoing activity that was directly and reproducibly related to the spontaneous spikes of a single neuron was, on average, as high as 54\% of the amplitude of the visually evoked response that was directly related to optimal sensory stimulation, recorded optically. 6. Coherent activity was detected even at distant cortical sites up to 6 mm apart.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Arieli, A and Shoham, D and Hildesheim, R and Grinvald, A}, Date-Added = {2011-04-05 12:27:01 -0400}, Date-Modified = {2011-04-05 12:27:21 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {optical physiology; imaging; intrinsic signal; optics; voltage sensor; optical imaging; microscopy}, Mesh = {Animals; Cats; Diagnostic Imaging; Electroencephalography; Evoked Potentials; Image Processing, Computer-Assisted; Neurons; Photic Stimulation; Time Factors; Visual Cortex}, Month = {May}, Number = {5}, Pages = {2072-93}, pmid = {7623099}, Pst = {ppublish}, Title = {Coherent spatiotemporal patterns of ongoing activity revealed by real-time optical imaging coupled with single-unit recording in the cat visual cortex}, Volume = {73}, Year = {1995}, url = {papers/Arieli_JNeurophysiol1995.pdf}} @article{Hill:1949, Author = {Hill, D K and Keynes, R D}, Date-Added = {2011-03-30 10:39:27 -0400}, Date-Modified = {2011-03-30 10:40:09 -0400}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {optical physiology; imaging; intrinsic signal; optics; Technique; optical imaging; Classical/physiology}, Month = {May}, Number = {3}, Pages = {278-81}, Pmc = {PMC1392485}, pmid = {16991859}, Pst = {ppublish}, Title = {Opacity changes in stimulated nerve}, Volume = {108}, Year = {1949}, url = {papers/Hill_JPhysiol1949.pdf}} @article{Lieke:1989, Author = {Lieke, E E and Frostig, R D and Arieli, A and Ts'o, D Y and Hildesheim, R and Grinvald, A}, Date-Added = {2011-03-28 12:35:32 -0400}, Date-Modified = {2011-09-12 11:19:12 -0400}, Journal = {Annu Rev Physiol}, Journal-Full = {Annual review of physiology}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics; Technique; review; optical imaging}, Mesh = {Animals; Cell Communication; Cerebral Cortex; Coloring Agents; Diagnostic Imaging; Electrophysiology; Humans; Neurons; Optics and Photonics; Time Factors}, Pages = {543-59}, pmid = {2653196}, Pst = {ppublish}, Title = {Optical imaging of cortical activity: real-time imaging using extrinsic dye-signals and high resolution imaging based on slow intrinsic-signals}, Volume = {51}, Year = {1989}, url = {papers/Lieke_AnnuRevPhysiol1989.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.ph.51.030189.002551}} @article{Bonhoeffer:1991, Abstract = {The mammalian cortex is organized in a columnar fashion: neurons lying below each other from the pia to the white matter usually share many functional properties. Across the cortical surface, cells with similar response properties are also clustered together, forming elongated bands or patches. Some response properties, such as orientation preference in the visual cortex, change gradually across the cortical surface forming 'orientation maps'. To determine the precise layout of iso-orientation domains, knowledge of responses not only to one but to many stimulus orientations is essential. Therefore, the exact depiction of orientation maps has been hampered by technical difficulties and remained controversial for almost thirty years. Here we use in vivo optical imaging based on intrinsic signals to gather information on the responses of a piece of cortex to gratings in many different orientations. This complete set of responses then provides detailed information on the structure of the orientation map in a large patch of cortex from area 18 of the cat. We find that cortical regions that respond best to one orientation form highly ordered patches rather than elongated bands. These iso-orientation patches are organized around 'orientation centres', producing pinwheel-like patterns in which the orientation preference of cells is changing continuously across the cortex. We have also analysed our data for fast changes in orientation preference and find that these 'fractures' are limited to the orientation centres. The pinwheels and orientation centres are such a prominent organizational feature that it should be important to understand their development as well as their function in the processing of visual information.}, Author = {Bonhoeffer, T and Grinvald, A}, Date-Added = {2011-03-28 12:33:57 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics; cat; visual system; visual cortex; function}, Mesh = {Animals; Brain Mapping; Cats; Image Processing, Computer-Assisted; Orientation; Visual Cortex; Visual Perception}, Month = {Oct}, Number = {6343}, Pages = {429-31}, pmid = {1896085}, Pst = {ppublish}, Title = {Iso-orientation domains in cat visual cortex are arranged in pinwheel-like patterns}, Volume = {353}, Year = {1991}, url = {papers/Bonhoeffer_Nature1991.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/353429a0}} @article{Tso:1990, Abstract = {A high spatial resolution optical imaging system was developed to visualize cerebral cortical activity in vivo. This method is based on activity-dependent intrinsic signals and does not use voltage-sensitive dyes. Images of the living monkey striate (VI) and extrastriate (V2) visual cortex, taken during visual stimulation, were analyzed to yield maps of the distribution of cells with various functional properties. The cytochrome oxidase--rich blobs of V1 and the stripes of V2 were imaged in the living brain. In V2, no ocular dominance organization was seen, while regions of poor orientation tuning colocalized to every other cytochrome oxidase stripe. The orientation tuning of other regions of V2 appeared organized as modules that are larger and more uniform than those in V1.}, Author = {Ts'o, D Y and Frostig, R D and Lieke, E E and Grinvald, A}, Date-Added = {2011-03-28 12:24:45 -0400}, Date-Modified = {2011-03-28 12:26:12 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics; monkey; visual cortex; visual system}, Mesh = {Action Potentials; Animals; Diagnostic Imaging; Electric Stimulation; Electron Transport Complex IV; Electrophysiology; Macaca; Motor Neurons; Neurons, Afferent; Synapses; Vision, Ocular; Visual Cortex}, Month = {Jul}, Number = {4967}, Pages = {417-20}, pmid = {2165630}, Pst = {ppublish}, Title = {Functional organization of primate visual cortex revealed by high resolution optical imaging}, Volume = {249}, Year = {1990}, url = {papers/Ts'o_Science1990.pdf}} @article{Orbach:1985, Abstract = {We have investigated the use of optical methods for monitoring neuron activity in mammalian cortex. The cortex was stained with a voltage-sensitive dye and fluorescence was simultaneously measured from 124 areas using a photodiode array. Optical signals were detected in rat somatosensory cortex in response to small whisker movements and in visual cortex in response to light flashes to the eye. Relatively large signals were obtained during focal interictal epileptiform discharges induced by bicuculline. The measuring system had a time resolution of milliseconds and a spatial resolution of a few hundred micrometers. Simultaneous, multi-site optical recordings of activity may provide a new and potentially powerful method for studying function and dysfunction in mammalian cortex.}, Author = {Orbach, H S and Cohen, L B and Grinvald, A}, Date-Added = {2011-03-28 12:19:45 -0400}, Date-Modified = {2011-03-28 12:24:28 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {optical physiology; imaging; intrinsic signal; optics; rat; visual cortex; visual systems}, Mesh = {Animals; Brain Mapping; Electrophysiology; Photic Stimulation; Somatosensory Cortex; Vibrissae; Visual Cortex}, Month = {Jul}, Number = {7}, Pages = {1886-95}, pmid = {4020423}, Pst = {ppublish}, Title = {Optical mapping of electrical activity in rat somatosensory and visual cortex}, Volume = {5}, Year = {1985}, url = {papers/Orbach_JNeurosci1985.pdf}} @article{Salzberg:1977, Abstract = {1. Using an optical method for measuring membrane potential, we have been able to monitor action-potential activity simultaneously in 14 neurons of the supraesophageal ganglion of the barnacle. 2. Under favorable conditions, 4-mV synaptic potentials could also be detected optically.}, Author = {Salzberg, B M and Grinvald, A and Cohen, L B and Davila, H V and Ross, W N}, Date-Added = {2011-03-28 12:15:05 -0400}, Date-Modified = {2011-03-28 12:17:46 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Central Nervous System; Electronics, Medical; Methods; Neurons; Thoracica}, Month = {Nov}, Number = {6}, Pages = {1281-91}, pmid = {925730}, Pst = {ppublish}, Title = {Optical recording of neuronal activity in an invertebrate central nervous system: simultaneous monitoring of several neurons}, Volume = {40}, Year = {1977}, url = {papers/Salzberg_JNeurophysiol1977.pdf}} @article{Grinvald:1984, Abstract = {A major obstacle to understanding the function and development of the vertebrate brain is the difficulty in monitoring dynamic patterns of electrical activity in the millesecond time domain; this has limited investigations of such phenomena as modular organization of functional units, seizure activities and spreading depression. The use of voltage-sensitive dyes and the recent development of the use of an array of photodiodes has provided a unique technique for monitoring the dynamic patterns of electrical activity in real time from a variety of invertebrate or vertebrate neuronal preparations including the rat cortex. In the present study, this technique has been used to investigate the intact optic tectum of the frog. We demonstrate that optical measurements can be used for real-time imaging of spatio-temporal patterns of neuronal responses and for identification of functional units evoked by natural visual stimuli. We report also the structure of the new voltage-sensitive probe that facilitates the in vivo applications of this technique.}, Author = {Grinvald, A and Anglister, L and Freeman, J A and Hildesheim, R and Manker, A}, Date = {1984 Apr 26-May 2}, Date-Added = {2011-03-28 11:46:19 -0400}, Date-Modified = {2011-03-28 11:47:07 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics; optic tectum; voltage sensor; optical imaging; microscopy}, Mesh = {Animals; Evoked Potentials; Fluorescent Dyes; Neurons; Photic Stimulation; Rana ridibunda; Retina; Superior Colliculi; Visual Pathways; Visual Perception}, Number = {5962}, Pages = {848-50}, pmid = {6717577}, Pst = {ppublish}, Title = {Real-time optical imaging of naturally evoked electrical activity in intact frog brain}, Volume = {308}, Year = {1984}, url = {papers/Grinvald_Nature1984.pdf}} @article{Farber:1983, Abstract = {An optical method involving the use of a laser and a novel fluorescent dye as a photostimulation probe has been developed to identify presynaptic neurons in a large ensemble of cells. Illumination of an extracellularly stained neuron by the laser microbeam evokes action potentials. With this technique an interneuron connecting identified leech neurons was quickly located. The method speeds up the elucidation of neuronal networks, especially when small cells are involved.}, Author = {Farber, I C and Grinvald, A}, Date-Added = {2011-03-28 11:43:58 -0400}, Date-Modified = {2011-03-28 11:44:39 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics; activity manipulation;}, Mesh = {Action Potentials; Animals; Electric Conductivity; Fluorescent Dyes; Interneurons; Lasers; Leeches; Membrane Potentials; Mollusca; Neural Pathways; Neurons; Photic Stimulation; Ranidae; Synapses}, Month = {Dec}, Number = {4627}, Pages = {1025-7}, pmid = {6648515}, Pst = {ppublish}, Title = {Identification of presynaptic neurons by laser photostimulation}, Volume = {222}, Year = {1983}, url = {papers/Farber_Science1983.pdf}} @article{Cohen:1968, Author = {Cohen, L B and Keynes, R D and Hille, B}, Date-Added = {2011-03-28 10:54:08 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Axons; Birefringence; Crustacea; Light; Membrane Potentials; Models, Neurological; Neurons}, Month = {May}, Number = {5140}, Pages = {438-41}, pmid = {5649693}, Pst = {ppublish}, Title = {Light scattering and birefringence changes during nerve activity}, Volume = {218}, Year = {1968}, url = {papers/Cohen_Nature1968.pdf}} @article{Tasaki:1968, Author = {Tasaki, I and Watanabe, A and Sandlin, R and Carnay, L}, Date-Added = {2011-03-28 10:54:04 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Birefringence; Crustacea; Electric Stimulation; Fluorescence; Optics and Photonics; Synaptic Transmission}, Month = {Nov}, Number = {3}, Pages = {883-8}, Pmc = {PMC305410}, pmid = {4301149}, Pst = {ppublish}, Title = {Changes in fluorescence, turbidity, and birefringence associated with nerve excitation}, Volume = {61}, Year = {1968}, url = {papers/Tasaki_ProcNatlAcadSciUSA1968.pdf}} @article{Davila:1973, Author = {Davila, H V and Salzberg, B M and Cohen, L B and Waggoner, A S}, Date-Added = {2011-03-28 10:54:00 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {Nat New Biol}, Journal-Full = {Nature: New biology}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Axons; Decapodiformes; Fluorescent Dyes; Membrane Potentials; Methods; Oxazoles; Piperazines; Sulfonic Acids}, Month = {Jan}, Number = {109}, Pages = {159-60}, pmid = {4512623}, Pst = {ppublish}, Title = {A large change in axon fluorescence that provides a promising method for measuring membrane potential}, Volume = {241}, Year = {1973}} @article{Muralt:1975, Abstract = {Among the signs of activity in excitable membranes, the action current (electrical spike) has been extensively studied. Recently, a new approach with optical methods has been rewarding. In nerves, a transient, rapid change of light scanning, birefringence and induced fluorescence can be observed during the passage of the action current. These optical effects are synchronous with the electrical spike and are therefore called the optical spikes. Birefringence decreases during excitation in the giant axon of the squid, the walking nerves of Maia, the vagus nerve of the rabbit, but it increases in the olfactory nerve of the pike, which contains 4 million nonmedullated nerve fibres. Light scattering increases or decreases depending on the angle of observation. Vitally stained nerves with fluorescent probes show an increase and a shift in the wavelength distribution of the fluorescent spike.}, Author = {von Muralt, A}, Date-Added = {2011-03-28 10:53:55 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Axons; Birefringence; Decapodiformes; Fishes; Fluorescence; Light; Models, Biological; Olfactory Nerve; Peripheral Nerves; Rabbits; Scattering, Radiation; Temperature; Vagus Nerve}, Month = {Jun}, Number = {908}, Pages = {411-23}, pmid = {238238}, Pst = {ppublish}, Title = {The optical spike}, Volume = {270}, Year = {1975}, url = {papers/Muralt_PhilosTransRSocLondBBiolSci1975.pdf}} @article{Grinvald:1977, Author = {Grinvald, A and Salzberg, B M and Cohen, L B}, Date-Added = {2011-03-28 10:53:50 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Central Nervous System; Ganglia; Light; Neurons; Thoracica}, Month = {Jul}, Number = {5616}, Pages = {140-2}, pmid = {593306}, Pst = {ppublish}, Title = {Simultaneous recording from several neurones in an invertebrate central nervous system}, Volume = {268}, Year = {1977}, url = {papers/Grinvald_Nature1977.pdf}} @article{Cohen:1978, Author = {Cohen, L B and Salzberg, B M and Grinvald, A}, Date-Added = {2011-03-28 10:53:46 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Axons; Central Nervous System; Decapodiformes; Membrane Potentials; Neurons; Spectrophotometry; Thoracica}, Pages = {171-82}, pmid = {386900}, Pst = {ppublish}, Title = {Optical methods for monitoring neuron activity}, Volume = {1}, Year = {1978}, url = {papers/Cohen_AnnuRevNeurosci1978.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.ne.01.030178.001131}} @article{Iwasa:1980, Abstract = {Swelling of nerve fibers during the action potential was demonstrated by three different methods. Generation of a propagated nerve impulse in a crab nerve produced an outward movement of 50 to 100 angstroms of the nerve surfce and a rise in swelling pressure on the order of 5 dynes per square centimeter. In squid giant axons, the amplitude of the observed outward movement of the surface was small.}, Author = {Iwasa, K and Tasaki, I and Gibbons, R C}, Date-Added = {2011-03-28 10:53:41 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Axons; Brachyura; Decapodiformes; Hydrostatic Pressure; Time Factors}, Month = {Oct}, Number = {4467}, Pages = {338-9}, pmid = {7423196}, Pst = {ppublish}, Title = {Swelling of nerve fibers associated with action potentials}, Volume = {210}, Year = {1980}} @article{Tasaki:1981, Abstract = {1. By using a Fotonic sensor, it was found possible to record rapid mechanical responses of the crab nerve without a signal averager. 2. In squid giant axons, the peak of swelling was shown to coincide fairly accurately with the peak of the action potential. 3. Associated with propagation of an action potential along a squid giant axon, there is a small decrease followed by an increase in the length of the axon. 4. It was emphasized that both mechanical and birefringence responses of the squid axon are diphasic. 5. The origin of the mechanical responses in axons is discussed on the basis of the theories proposed by LOEB, HOBER and TEORELL.}, Author = {Tasaki, I and Iwasa, K}, Date-Added = {2011-03-28 10:53:36 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {J Physiol (Paris)}, Journal-Full = {Journal de physiologie}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Axons; Brachyura; Decapodiformes; Methods; Neurons}, Month = {May}, Number = {9}, Pages = {1055-9}, pmid = {7346626}, Pst = {ppublish}, Title = {Rapid mechanical changes in crab nerve and squid axon during action potentials}, Volume = {77}, Year = {1981}} @article{Grinvald:1982, Abstract = {1. Voltage-sensitive membrane-bound dyes and a matrix of 100 photodetectors were used to detect the spread of evoked electrical activity at the CA1 region of rat hippocampus slices. A display processor was designed in order to visualize the spread of electrical activity in slow motion.2. The stimulation of the Schaffer collateral-commissural path in the stratum radiatum evoked short latency (2-4 msec) fast optical signals, followed by longer latency (4-15 msec) slow signals which decayed within 20-50 msec. Multiple fast signals were frequently detected at the stratum pyramidale; they propagated toward the stratum oriens with an approximate conduction velocity of 0.1 m/sec.3. The fast signals were unaltered in a low Ca(2+) high Mg(2+) medium but were blocked by tetrodotoxin. These signals probably represent action potentials in the Schaffer collateral axons. Their conduction velocity was about 0.2 m/sec and their refractory period about 3-4 msec.4. The slow signals were absent in a low Ca(2+) medium and probably represent excitatory post-synaptic potentials (e.p.s.p.s) generated in the apical dendrites of the pyramidal cells. They were generated in the stratum radiatum, where the presynaptic signals were seen, and spread into somata and basal dendrites (the stratum pyramidale and oriens, respectively).5. The timing of the signals with fast rise-time, which were detected at the statum pyramidale, approximately coincided with the timing of the extracellularly recorded field potentials. These multiple discharges probably represent action potentials of the pyramidal cells. They spread back into the apical dendrites but with significant attenuation of the amplitudes of the high frequency components of the pyramidal action potentials.6. Hyperpolarizing potentials could be detected when strong stimuli were applied to the stratum radiatum or alveus. The net hyperpolarizations were detected only in the stratum pyramidale and the border region between the stratum pyramidale and radiatum. Frequently the inhibition was masked by the large e.p.s.p.s. However, its existence could be demonstrated by treatment of the slice with picrotoxin or a low Cl(-) medium. Under these conditions a long-lasting depolarization of the apical dedrites was evoked by the stimulation. This was associated with an increase of the multiple discharges in the stratum pyramidale and oriens.7. These studies illustrate the usefulness of voltage-sensitive dyes in the analysis of passive and active electrical properties, pharmacological properties and synaptic connexions in mammalian brain slices, at the level both of small neuronal elements (dendrites, axons) and of synchronously active neuronal populations.}, Author = {Grinvald, A and Manker, A and Segal, M}, Date-Added = {2011-03-28 10:53:28 -0400}, Date-Modified = {2011-03-28 11:00:17 -0400}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {optical physiology; imaging; intrinsic signal; voltage sensor; optics}, Mesh = {Action Potentials; Animals; Axons; Calcium; Coloring Agents; Electric Conductivity; Hippocampus; Magnesium; Male; Membrane Potentials; Photometry; Rats; Rats, Inbred Strains; Synapses; Tetrodotoxin}, Month = {Dec}, Pages = {269-91}, Pmc = {PMC1197248}, pmid = {7182467}, Pst = {ppublish}, Title = {Visualization of the spread of electrical activity in rat hippocampal slices by voltage-sensitive optical probes}, Volume = {333}, Year = {1982}} @article{Fite:1999, Abstract = {A direct pathway from the retina to the dorsal raphe nucleus (DRN) has been demonstrated in both albino rats and Mongolian gerbils. Following intraocular injection of cholera toxin subunit B (CTB), a diffuse stream of CTB-positive, fine-caliber optic axons emerged from the optic tract at the level of the pretectum/anterior mesencephalon. In gerbils, CTB-positive axons descended ventromedially into the periaqueductal gray, moving caudally and arborizing extensively throughout the DRN. In rats, the retinal-DRN projection comprised fewer, but larger caliber, axons, which arborized in a relatively restricted region of the lateral and ventral DRN. Following injection of CTB into the lateral DRN, retrogradely labeled ganglion cells (GCs) were observed in whole-mount retinas of both species. In gerbils, CTB-positive GCs were distributed over the entire retina, and a nearest-neighbor analysis of CTB-positive GCs showed significant regularity (nonrandomness) in their distribution. The overall distribution of gerbil GC soma diameters ranged from 8 to 22 micrometer and was skewed slightly towards the larger soma diameters. Based on an adaptive mixtures model statistical analysis, two Gaussian distributions appeared to comprise the total GC distribution, with mean soma diameters of 13 (SEM +/-1.7) micrometer, and 17 (SEM +/-1.5) micrometer, respectively. In rats, many fewer CTB-positive GCs were labeled following CTB injections into the lateral DRN, and nearly all occurred in the inferior retina. The total distribution of rat GC soma diameters was similar to that in gerbils and also was skewed towards the larger soma diameters. Major differences observed in the extent and configuration of the retinal-DRN pathway may be related to the diurnal/crepuscular vs. nocturnal habits of these two species.}, Author = {Fite, K V and Janusonis, S and Foote, W and Bengston, L}, Date-Added = {2011-03-22 23:02:48 -0400}, Date-Modified = {2011-03-22 23:03:11 -0400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {retinopetal;Efferent Pathways;connectivity;Circuit structure-function;circuitry;retina;visual system;Serotonin;mouse;mice;dorsal raphe}, Mesh = {Animals; Axons; Cell Count; Cell Size; Cholera Toxin; Dendrites; Gerbillinae; Immunohistochemistry; Peptide Fragments; Raphe Nuclei; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells; Visual Pathways}, Month = {Nov}, Number = {4}, Pages = {469-84}, pmid = {10531540}, Pst = {ppublish}, Title = {Retinal afferents to the dorsal raphe nucleus in rats and Mongolian gerbils}, Volume = {414}, Year = {1999}, url = {papers/Fite_JCompNeurol1999.pdf}} @article{Reperant:2000, Abstract = {The present study demonstrated a direct serotonergic retinopetal projection in the mouse stemming from the lateral portion of the dorsal raphe nucleus bilaterally. A double-labeling technique was employed combining: (1) radioautography and retrograde axonal tracing following intraocular injection of [(3)H] 5-HT and (2) immunocytochemical identification of endogenous 5-HT. Radiolabeled neurons were only observed within the dorsal raphe nucleus and were always double-labeled with the 5-HT antibody. The radiolabeling appeared to be specific resulting from the retrograde transport of a radioactive 5-HT derivative product following uptake of the neurotransmitter by intraretinal terminals.}, Author = {Rep{\'e}rant, J and Araneda, S and Miceli, D and Medina, M and Rio, J P}, Date-Added = {2011-03-22 23:00:49 -0400}, Date-Modified = {2011-03-22 23:02:01 -0400}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {retinopetal;Efferent Pathways;connectivity;Circuit structure-function;circuitry;retina;visual system;Serotonin;mouse;mice;dorsal raphe}, Mesh = {Animals; Autoradiography; Axonal Transport; Biological Transport, Active; Efferent Pathways; Immunohistochemistry; Mice; Mice, Inbred C57BL; Raphe Nuclei; Retina; Serotonin; Synaptic Transmission}, Month = {Sep}, Number = {1-2}, Pages = {213-7}, pmid = {10996155}, Pst = {ppublish}, Title = {Serotonergic retinopetal projections from the dorsal raphe nucleus in the mouse demonstrated by combined [(3)H] 5-HT retrograde tracing and immunolabeling of endogenous 5-HT}, Volume = {878}, Year = {2000}, url = {papers/Repérant_BrainRes2000.pdf}} @article{Upton:2002, Abstract = {We have shown previously that raised levels of serotonin (5-hydroxytryptamine or 5-HT) during development prevent retinal ganglion cell axons from segregating into eye-specific regions in their principal targets: the superior colliculus and the dorsal lateral geniculate nucleus. Possible mediators of 5-HT in this system include its plasma membrane transporter, which is transiently expressed by a sub-population of retinal ganglion cells, and the presynaptic 5-HT(1B) receptor carried on retinal ganglion cell axons. We analysed the retinal projections of 5-HT(1B) knockout (n=15), serotonin transporter knockout (n=14), serotonin transporter/5-HT(1B) double knockout (n=4) and monoamine oxidase A/5-HT(1B) double knockout (n=3) mice. In all four different knockout mice, the ipsilateral retinal projection to the superior colliculus was more diffuse and lost its characteristic patchy distribution. The alterations were most severe in the serotonin transporter knockout mice, where the ipsilateral retinal fibres covered the entire rostrocaudal and mediolateral extent of the superior colliculus, whereas in the 5-HT(1B) and double knockout mice, fibres retracted from the caudal and lateral superior colliculus. Abnormalities in the 5-HT(1B) knockout mice appeared only after postnatal day (P) 4. Treatment with parachlorophenylalanine (at P1-P12) to decrease serotonin levels caused an exuberance of the ipsilateral retinal fibres throughout the superior colliculus (n=9). In the dorsal lateral geniculate nucleus in contrast, the distribution and size of the ipsilateral retinal projection was normal in all four knockout mice. In the serotonin transporter knockout mice however, the contralateral retinal fibres failed to retract from the mediodorsal dorsal lateral geniculate nucleus, an abnormality that was reversed by early treatment with parachlorophenylalanine and in the serotonin transporter/5-HT(1B) double knockout. OUR OBSERVATIONS INDICATE: (1) that the lack of 5-HT transporter and the associated changes in 5-HT levels impair the segregation of retinal axons in both the superior colliculus and the dorsal lateral geniculate nucleus; (2) that 5-HT and 5-HT(1B) receptors are necessary for the normal refinement of the ipsilateral retinal fibres in the superior colliculus, but are not essential for the establishment of eye-specific segregation in the thalamus. Thus, both an excess and a lack of 5-HT affect the refinement of the superior colliculus retinal projection, while the establishment of eye-specific patterns in the dorsal lateral geniculate nucleus appears not to be sensitive to the lack of 5-HT or 5-HT(1B) receptors.}, Author = {Upton, A L and Ravary, A and Salichon, N and Moessner, R and Lesch, K-P and Hen, R and Seif, I and Gaspar, P}, Date-Added = {2011-03-22 22:52:05 -0400}, Date-Modified = {2011-03-22 22:58:23 -0400}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {retinopetal;Superior Colliculus;Efferent Pathways;Serotonin;axons;mouse;Mice;Circuit structure-function;circuitry;connectivity}, Mesh = {Animals; Axons; Carrier Proteins; Fenclonine; Geniculate Bodies; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Monoamine Oxidase; Nerve Tissue Proteins; Receptor, Serotonin, 5-HT1B; Receptors, Serotonin; Retinal Ganglion Cells; Serotonin Plasma Membrane Transport Proteins; Superior Colliculi; Visual Pathways}, Number = {3}, Pages = {597-610}, pmid = {12031347}, Pst = {ppublish}, Title = {Lack of 5-HT(1B) receptor and of serotonin transporter have different effects on the segregation of retinal axons in the lateral geniculate nucleus compared to the superior colliculus}, Volume = {111}, Year = {2002}, url = {papers/Upton_Neuroscience2002.pdf}} @article{Upton:1999, Abstract = {Retinal ganglion cell (RGCs) project to the ipsilateral and contralateral sides of the brain in the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC). Projections from both eyes are initially intermingled until postnatal day 3 (P3) but segregate into eye-specific layers by P8. We report that this segregation does not occur in monoamine oxidase A knock-out mice (MAOA-KO) that have elevated brain levels of serotonin (5-HT) and noradrenaline. The abnormal development of retinal projections can be reversed by inhibiting 5-HT synthesis from P0 to P15. We found that in MAOA-KO mice, 5-HT accumulates in a subpopulation of RGCs and axons during embryonic and early postnatal development. The RGCs do not synthesize 5-HT but reuptake the amine from the extracellular space. In both MAOA-KO and normal mice, high-affinity uptake of 5-HT and serotonin transporter (SERT) immunoreactivity are observed in retinal axons from the optic cup to retinal terminal fields in the SC and dLGN. In the dLGN, transient SERT labeling corresponds predominantly to the ipsilateral retinal projection fields. We show that, in addition to SERT, developing RGCs also transiently express the vesicular monoamine transporter gene VMAT2: thus, retinal axons could store 5-HT in synaptic vesicles and possibly use it as a borrowed neurotransmitter. Finally we show that the 5-HT-1B receptor gene is expressed by RGCs throughout the retina from E15 until adult life. Activation of this receptor is known, from previous studies, to reduce retinotectal activity; thus 5-HT in excess could inhibit activity-dependent segregation mechanisms. A hypothesis is proposed whereby, during normal development, localized SERT expression could confer specific neurotransmission properties on a subset of RGCs and could be important in the fine-tuning of retinal projections.}, Author = {Upton, A L and Salichon, N and Lebrand, C and Ravary, A and Blakely, R and Seif, I and Gaspar, P}, Date-Added = {2011-03-22 22:43:23 -0400}, Date-Modified = {2011-03-22 22:43:50 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {retina;retinopetal;axons;connectivity;Circuit structure-function;Serotonin;retinal wave paper;dorsal raphe;Sleep;centrifugal;Efferent Pathways}, Mesh = {Animals; Carrier Proteins; Functional Laterality; Geniculate Bodies; Membrane Glycoproteins; Membrane Transport Proteins; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Monoamine Oxidase; Nerve Tissue Proteins; Norepinephrine; Retina; Retinal Ganglion Cells; Serotonin; Serotonin Plasma Membrane Transport Proteins; Superior Colliculi; Visual Pathways}, Month = {Aug}, Number = {16}, Pages = {7007-24}, pmid = {10436056}, Pst = {ppublish}, Title = {Excess of serotonin (5-HT) alters the segregation of ispilateral and contralateral retinal projections in monoamine oxidase A knock-out mice: possible role of 5-HT uptake in retinal ganglion cells during development}, Volume = {19}, Year = {1999}, url = {papers/Upton_JNeurosci1999.pdf}} @article{Takaura:2011, Abstract = {In the primate brain, the primary visual cortex (V1) is a major source of visual information processing in the cerebral cortex, although some patients and monkeys with damage to the V1 show visually guided behaviors in the visual field affected by the damage. Until now, behaviors of the surviving brain regions after damage to V1 and their contribution to the residual visual functions remain unclear. Here, we report that the monkeys with a unilateral lesion of V1 can make not only visually guided saccades but also memory-guided saccades (MGS) into the affected visual field. Furthermore, while the monkeys were performing the MGS task, sustained activity was observed in a large fraction of the neurons in the superior colliculus ipsilateral to the lesion, which has been supposed as a key node for recovery after damage to V1. These neurons maintained the spatial information throughout the delay period regardless of whether they exhibited saccadic bursts or not, which was not the case on the intact side. Error analysis revealed that the sustained activity was correlated with monkeys' behavioral outcome. These results suggest that the ipsilesional SC might function as a neural substrate for spatial memory in the affected visual field. Our findings provide new insight into the understanding of the compensatory mechanisms after damage to V1.}, Author = {Takaura, Kana and Yoshida, Masatoshi and Isa, Tadashi}, Date-Added = {2011-03-22 17:47:44 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Superior Colliculus;optic tectum;visual system;Spatial Behavior;Memory;Visual Cortex;monkey;blindsight;Electrophysiology;extracellular;Saccades;neurological disorder;lesion}, Month = {Mar}, Number = {11}, Pages = {4233-41}, pmid = {21411664}, Pst = {ppublish}, Title = {Neural substrate of spatial memory in the superior colliculus after damage to the primary visual cortex}, Volume = {31}, Year = {2011}, url = {papers/Takaura_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5143-10.2011}} @article{Greferath:2009, Abstract = {The vertebrate retina receives histaminergic input from the brain via retinopetal axons that originate from perikarya in the posterior hypothalamus. In the nervous system, histamine acts on three G-protein-coupled receptors, histamine receptor (HR) 1, HR2 and HR3. In order to look for potential cellular targets of histamine in the mouse retina, we have examined the retina for the expression of histamine and the presence of these three receptors. Consistent with studies of retina from other vertebrates, histamine was only found in retinopetal axons, which coursed extensively through the ganglion cell and inner plexiform layers. mRNA for all three receptors was expressed in the mouse retina, and immunohistochemical studies further localized HR1 and HR2. HR1 immunoreactivity was observed on dopaminergic amacrine cells, calretinin-positive ganglion cells and axon bundles in the ganglion cell layer. Furthermore, a distinct group of processes in the inner plexiform layer was labeled, which most likely represents the processes of cholinergic amacrine cells. HR2 immunoreactivity was observed on the processes and cell bodies of the primary glial cells of the mammalian retina, the M{\"u}ller cells. This distribution of histamine and its receptors is consistent with a brain-derived source of histamine acting on diverse populations of cells in the retina, including both neurons and glia.}, Author = {Greferath, U and Kambourakis, M and Barth, C and Fletcher, E L and Murphy, M}, Date-Added = {2011-03-19 17:58:58 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {retinopetal;Efferent Pathways;retina;visual system;connectivity;Circuit structure-function;Sleep;histamine;Mouse;Anatomy;retinal wave paper}, Mesh = {Animals; Brain; Calcium-Binding Protein, Vitamin D-Dependent; Dopamine; Female; Histamine; Male; Mice; Mice, Inbred C57BL; Optic Nerve; RNA, Messenger; Receptors, Histamine H1; Receptors, Histamine H2; Retina}, Month = {Jan}, Number = {2}, Pages = {932-44}, pmid = {19015005}, Pst = {ppublish}, Title = {Characterization of histamine projections and their potential cellular targets in the mouse retina}, Volume = {158}, Year = {2009}, url = {papers/Greferath_Neuroscience2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2008.10.034}} @article{Gastinger:2006, Abstract = {Since 1892, anatomical studies have demonstrated that the retinas of mammals, including humans, receive input from the brain via axons emerging from the optic nerve. There are only a small number of these retinopetal axons, but their branches in the inner retina are very extensive. More recently, the neurons in the brain stem that give rise to these axons have been localized, and their neurotransmitters have been identified. One set of retinopetal axons arises from perikarya in the posterior hypothalamus and uses histamine, and the other arises from perikarya in the dorsal raphe and uses serotonin. These serotonergic and histaminergic neurons are not specialized to supply the retina; rather, they are a subset of the neurons that project via collaterals to many other targets in the central nervous system, as well. They are components of the ascending arousal system, firing most rapidly when the animal is awake and active. The contributions of these retinopetal axons to vision may be predicted from the known effects of serotonin and histamine on retinal neurons. There is also evidence suggesting that retinopetal axons play a role in the etiology of retinal diseases.}, Author = {Gastinger, Matthew J and Tian, Ning and Horvath, Tamas and Marshak, David W}, Date = {2006 Jul-Aug}, Date-Added = {2011-03-19 11:58:00 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Curr Eye Res}, Journal-Full = {Current eye research}, Keywords = {retina;retinopetal;axons;connectivity;Circuit structure-function;histamine;Serotonin;retinal wave paper;Hypothalamus;dorsal raphe;Sleep;centrifugal;Efferent Pathways}, Mesh = {Animals; Axons; Histamine; Humans; Optic Nerve; Retina; Serotonin; Signal Transduction}, Number = {7-8}, Pages = {655-67}, pmid = {16877274}, Pst = {ppublish}, Title = {Retinopetal axons in mammals: emphasis on histamine and serotonin}, Volume = {31}, Year = {2006}, url = {papers/Gastinger_CurrEyeRes2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/02713680600776119}} @article{Tzingounis:2006, Abstract = {Arc/Arg3.1 is an effector immediate-early gene implicated in the consolidation of memories. Although cloned a decade ago, the physiological role of Arc/Arg3.1 in the brain has remained elusive. Four papers in this issue of Neuron address this function. These studies show that Arc/Arg3.1 regulates endophilin 3 and dynamin 2, two components of the endocytosis machinery. Genetic ablation of Arc/Arg3.1 in mice or overexpression in culture suggest that Arc/Arg3.1 regulates AMPA receptor trafficking and synaptic plasticity. Finally, Arc/Arg3.1 knockout mice show memory retention deficits. These recent developments provide new insights into the function of this popular activity-dependent neuronal marker.}, Author = {Tzingounis, Anastassios V and Nicoll, Roger A}, Date-Added = {2011-03-17 22:16:38 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Immediate-Early;genes;review;experience dependent plasticity;synapses;Memory;homeostatic plasticity;Long-Term Potentiation;Long-Term Depression (Physiology);mouse;mice;transgenic}, Mesh = {Animals; Cytoskeletal Proteins; Gene Expression; Memory; Nerve Tissue Proteins; Neuronal Plasticity}, Month = {Nov}, Number = {3}, Pages = {403-7}, pmid = {17088207}, Pst = {ppublish}, Title = {Arc/Arg3.1: linking gene expression to synaptic plasticity and memory}, Volume = {52}, Year = {2006}, url = {papers/Tzingounis_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.10.016}} @article{Loebrich:2009, Abstract = {The mammalian brain is plastic in the sense that it shows a remarkable capacity for change throughout life. The contribution of neuronal activity to brain plasticity was first recognized in relation to critical periods of development, when manipulating the sensory environment was found to profoundly affect neuronal morphology and receptive field properties. Since then, a growing body of evidence has established that brain plasticity extends beyond development and is an inherent feature of adult brain function, spanning multiple domains, from learning and memory to adaptability of primary sensory maps. Here we discuss evolution of the current view that plasticity of the adult brain derives from dynamic tuning of transcriptional control mechanisms at the neuronal level, in response to external and internal stimuli. We then review the identification of "plasticity genes" regulated by changes in the levels of electrical activity, and how elucidating their cellular functions has revealed the intimate role transcriptional regulation plays in fundamental aspects of synaptic transmission and circuit plasticity that occur in the brain on an every day basis.}, Author = {Loebrich, Sven and Nedivi, Elly}, Date-Added = {2011-03-17 18:15:29 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Physiol Rev}, Journal-Full = {Physiological reviews}, Keywords = {Immediate-Early;genes;21 Activity-development;experience dependent plasticity;review}, Mesh = {Animals; Gene Expression; Genes, Immediate-Early; Humans; Nervous System Physiological Phenomena; Neuronal Plasticity; Signal Transduction; Synapses; Transcription, Genetic; Transcriptional Activation}, Month = {Oct}, Number = {4}, Pages = {1079-103}, Pmc = {PMC2828052}, pmid = {19789377}, Pst = {ppublish}, Title = {The function of activity-regulated genes in the nervous system}, Volume = {89}, Year = {2009}, url = {papers/Loebrich_PhysiolRev2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/physrev.00013.2009}} @article{Kawashima:2009, Abstract = {The neuronal immediate early gene Arc/Arg-3.1 is widely used as one of the most reliable molecular markers for intense synaptic activity in vivo. However, the cis-acting elements responsible for such stringent activity dependence have not been firmly identified. Here we combined luciferase reporter assays in cultured cortical neurons and comparative genome mapping to identify the critical synaptic activity-responsive elements (SARE) of the Arc/Arg-3.1 gene. A major SARE was found as a unique approximately 100-bp element located at >5 kb upstream of the Arc/Arg-3.1 transcription initiation site in the mouse genome. This single element, when positioned immediately upstream of a minimal promoter, was necessary and sufficient to replicate crucial properties of endogenous Arc/Arg-3.1's transcriptional regulation, including rapid onset of transcription triggered by synaptic activity and low basal expression during synaptic inactivity. We identified the major determinants of SARE as a unique cluster of neuronal activity-dependent cis-regulatory elements consisting of closely localized binding sites for CREB, MEF2, and SRF. Consistently, a SARE reporter could readily trace and mark an ensemble of cells that have experienced intense activity in the recent past in vivo. Taken together, our work uncovers a novel transcriptional mechanism by which a critical 100-bp element, SARE, mediates a predominant component of the synapse-to-nucleus signaling in ensembles of Arc/Arg-3.1-positive activated neurons.}, Author = {Kawashima, Takashi and Okuno, Hiroyuki and Nonaka, Mio and Adachi-Morishima, Aki and Kyo, Nan and Okamura, Michiko and Takemoto-Kimura, Sayaka and Worley, Paul F and Bito, Haruhiko}, Date-Added = {2011-03-17 17:50:49 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Immediate-Early;genes;21 Activity-development;experience dependent plasticity;Transcription Factors;Regulatory Sequences}, Mesh = {Animals; Binding Sites; Cell Nucleus; Cyclic AMP Response Element-Binding Protein; Cytoskeletal Proteins; Gene Expression Regulation; Genomics; Mice; Myogenic Regulatory Factors; Nerve Tissue Proteins; Neurons; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Serum Response Factor; Signal Transduction; Synapses}, Month = {Jan}, Number = {1}, Pages = {316-21}, Pmc = {PMC2629236}, pmid = {19116276}, Pst = {ppublish}, Title = {Synaptic activity-responsive element in the Arc/Arg3.1 promoter essential for synapse-to-nucleus signaling in activated neurons}, Volume = {106}, Year = {2009}, url = {papers/Kawashima_ProcNatlAcadSciUSA2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0806518106}} @article{Harvey:2009, Abstract = {Hippocampal place cells encode spatial information in rate and temporal codes. To examine the mechanisms underlying hippocampal coding, here we measured the intracellular dynamics of place cells by combining in vivo whole-cell recordings with a virtual-reality system. Head-restrained mice, running on a spherical treadmill, interacted with a computer-generated visual environment to perform spatial behaviours. Robust place-cell activity was present during movement along a virtual linear track. From whole-cell recordings, we identified three subthreshold signatures of place fields: an asymmetric ramp-like depolarization of the baseline membrane potential, an increase in the amplitude of intracellular theta oscillations, and a phase precession of the intracellular theta oscillation relative to the extracellularly recorded theta rhythm. These intracellular dynamics underlie the primary features of place-cell rate and temporal codes. The virtual-reality system developed here will enable new experimental approaches to study the neural circuits underlying navigation.}, Author = {Harvey, Christopher D and Collman, Forrest and Dombeck, Daniel A and Tank, David W}, Date-Added = {2011-03-17 17:46:08 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Neurophysiology;Hippocampus;function;Electrophysiology;behavior;extracellular;Technique;Computer Graphics;21 Cortical oscillations}, Mesh = {Animals; Behavior, Animal; Hippocampus; Intracellular Space; Locomotion; Male; Membrane Potentials; Mice; Mice, Inbred C57BL; Neurons; Pyramidal Cells; Space Perception; Theta Rhythm; User-Computer Interface}, Month = {Oct}, Number = {7266}, Pages = {941-6}, Pmc = {PMC2771429}, pmid = {19829374}, Pst = {ppublish}, Title = {Intracellular dynamics of hippocampal place cells during virtual navigation}, Volume = {461}, Year = {2009}, url = {papers/Harvey_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08499}} @article{Inoue:2010, Abstract = {Formation of a new memory requires plasticity at the synaptic level. However, it has also been shown that the consolidation and the maintenance of such a new memory involve processes that necessitate active mRNA at the nucleus of the cell. How can robust changes in synaptic efficacy specifically drive new transcription and translation of new gene transcripts, and thus transform an otherwise transient plasticity into a long-lasting and stable one? In this article, we highlight the conceptual advance that was gained by the discovery of a potent Synaptic Activity-Responsive Element (SARE) found ∼7 kb upstream of the transcription initiation site of the neuronal immediate early gene Arc. The unique genomic structure of SARE, which contained adjacent and cooperative binding sites for three major activity-dependent transcription factors within a 100-bp locus, was associated with an unusual responsiveness to neuronal stimuli. Taken together, these findings shed light on a new class of transcriptional sensor with enhanced sensitivity to synaptic activity.}, Author = {Inoue, Masatoshi and Yagishita-Kyo, Nan and Nonaka, Mio and Kawashima, Takashi and Okuno, Hiroyuki and Bito, Haruhiko}, Date-Added = {2011-03-17 17:38:09 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Commun Integr Biol}, Journal-Full = {Communicative \& integrative biology}, Keywords = {Immediate-Early;genes;review;21 Activity-development;experience dependent plasticity;}, Month = {Sep}, Number = {5}, Pages = {443-6}, Pmc = {PMC2974076}, pmid = {21057636}, Pst = {ppublish}, Title = {Synaptic activity-responsive element (SARE): A unique genomic structure with an unusual sensitivity to neuronal activity}, Volume = {3}, Year = {2010}, url = {papers/Inoue_CommunIntegrBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.4161/cib.3.5.12287}} @article{Vazdarjanova:2002, Abstract = {The transcription of the immediate-early genes Arc and Homer 1a (H1a) is dynamically regulated in response to synaptic activity; their protein products function at the postsynaptic sites of excitatory synapses. Previous studies demonstrate a role for Arc in the maintenance of long-term potentiation and in memory consolidation processes and indicate a role for H1a in modifying glutamatergic signaling pathways. Using double-label fluorescence in situ hybridization, we demonstrate that Arc and H1a RNA expression is induced strongly in the same neurons of rat hippocampus and neocortex after exploration of a novel environment. These findings support the view that novel experience activates a cell-specific genomic program and that Arc and H1a may function in concert in the structural and functional modifications of dendrites that lead to long-term changes in synaptic efficacy.}, Author = {Vazdarjanova, Almira and McNaughton, Bruce L and Barnes, Carol A and Worley, Paul F and Guzowski, John F}, Date-Added = {2011-03-17 17:26:02 -0400}, Date-Modified = {2011-03-17 17:28:28 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Immediate-Early;genes;Technique;rat;Hippocampus;Imaging;microscopy;experience dependent plasticity;synapses;Fluorescence;frontiers review}, Mesh = {3' Untranslated Regions; Animals; Carrier Proteins; Cell Nucleus; Cytoskeletal Proteins; Dendrites; Electroshock; Exploratory Behavior; Genes, Immediate-Early; Hippocampus; In Situ Hybridization, Fluorescence; Male; Neocortex; Nerve Net; Nerve Tissue Proteins; Neuronal Plasticity; Neurons; Neuropeptides; Protein Isoforms; RNA, Messenger; Rats; Rats, Sprague-Dawley; Spatial Behavior}, Month = {Dec}, Number = {23}, Pages = {10067-71}, pmid = {12451105}, Pst = {ppublish}, Title = {Experience-dependent coincident expression of the effector immediate-early genes arc and Homer 1a in hippocampal and neocortical neuronal networks}, Volume = {22}, Year = {2002}, url = {papers/Vazdarjanova_JNeurosci2002.pdf}} @article{Alvarado:2009, Abstract = {Influences from the visual (AEV), auditory (FAES), and somatosensory (SIV) divisions of the cat anterior ectosylvian sulcus (AES) play a critical role in rendering superior colliculus (SC) neurons capable of multisensory integration. However, it is not known whether this is accomplished via their independent sensory-specific action or via some cross-modal cooperative action that emerges as a consequence of their convergence on SC neurons. Using visual-auditory SC neurons as a model, we examined how selective and combined deactivation of FAES and AEV affected SC multisensory (visual-auditory) and unisensory (visual-visual) integration capabilities. As noted earlier, multisensory integration yielded SC responses that were significantly greater than those evoked by the most effective individual component stimulus. This multisensory "response enhancement" was more evident when the component stimuli were weakly effective. Conversely, unisensory integration was dominated by the lack of response enhancement. During cryogenic deactivation of FAES and/or AEV, the unisensory responses of SC neurons were only modestly affected; however, their multisensory response enhancement showed a significant downward shift and was eliminated. The shift was similar in magnitude for deactivation of either AES subregion and, in general, only marginally greater when both were deactivated simultaneously. These data reveal that SC multisensory integration is dependent on the cooperative action of distinct subsets of unisensory corticofugal afferents, afferents whose sensory combination matches the multisensory profile of their midbrain target neurons, and whose functional synergy is specific to rendering SC neurons capable of synthesizing information from those particular senses.}, Author = {Alvarado, Juan Carlos and Stanford, Terrence R and Rowland, Benjamin A and Vaughan, J William and Stein, Barry E}, Date-Added = {2011-03-17 15:38:52 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Superior Colliculus;optic tectum;function;Behavior;multisensory integration;neocortex;connectivity;cat}, Mesh = {Acoustic Stimulation; Action Potentials; Analysis of Variance; Animals; Attention; Cats; Cerebral Cortex; Neural Pathways; Neurons; Photic Stimulation; Sensation; Sensory Thresholds; Superior Colliculi; Transition Temperature}, Month = {May}, Number = {20}, Pages = {6580-92}, Pmc = {PMC2805025}, pmid = {19458228}, Pst = {ppublish}, Title = {Multisensory integration in the superior colliculus requires synergy among corticocollicular inputs}, Volume = {29}, Year = {2009}, url = {papers/Alvarado_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0525-09.2009}} @article{Schachner:2009, Abstract = {The human capacity for music consists of certain core phenomena, including the tendency to entrain, or align movement, to an external auditory pulse [1-3]. This ability, fundamental both for music production and for coordinated dance, has been repeatedly highlighted as uniquely human [4-11]. However, it has recently been hypothesized that entrainment evolved as a by-product of vocal mimicry, generating the strong prediction that only vocal mimicking animals may be able to entrain [12, 13]. Here we provide comparative data demonstrating the existence of two proficient vocal mimicking nonhuman animals (parrots) that entrain to music, spontaneously producing synchronized movements resembling human dance. We also provide an extensive comparative data set from a global video database systematically analyzed for evidence of entrainment in hundreds of species both capable and incapable of vocal mimicry. Despite the higher representation of vocal nonmimics in the database and comparable exposure of mimics and nonmimics to humans and music, only vocal mimics showed evidence of entrainment. We conclude that entrainment is not unique to humans and that the distribution of entrainment across species supports the hypothesis that entrainment evolved as a by-product of selection for vocal mimicry.}, Author = {Schachner, Adena and Brady, Timothy F and Pepperberg, Irene M and Hauser, Marc D}, Date-Added = {2011-03-17 15:36:50 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {Spontaneous activity;entrainment;Superior Colliculus;optic tectum;function;Behavior;Cooperative Behavior;Motor Activity/physiology}, Mesh = {Animals; Auditory Perception; Behavior, Animal; Dancing; Databases, Factual; Humans; Music; Parrots; Periodicity; Video Recording; Vocalization, Animal; Voice}, Month = {May}, Number = {10}, Pages = {831-6}, pmid = {19409786}, Pst = {ppublish}, Title = {Spontaneous motor entrainment to music in multiple vocal mimicking species}, Volume = {19}, Year = {2009}, url = {papers/Schachner_CurrBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2009.03.061}} @article{Palagina:2009, Abstract = {Sensory deprivation caused by peripheral injury can trigger functional cortical reorganization across the initially silenced cortical area. It is proposed that intracortical connectivity enables recovery of function within such a lesion projection zone (LPZ), thus substituting lost subcortical input. Here, we investigated retinal lesion-induced changes in the function of lateral connections in the primary visual cortex of the adult rat. Using voltage-sensitive dye recordings, we visualized in millisecond-time resolution spreading synaptic activity across the LPZ. Shortly after lesion, the majority of neurons within the LPZ were subthresholdly activated by delayed propagation of activity that originated from unaffected cortical regions. With longer recovery time, latencies within the LPZ gradually decreased, and activation reached suprathreshold levels. Targeted electrode recordings confirmed that receptive fields of intra-LPZ neurons were displaced to the retinal lesion border while displaying normal orientation and direction selectivity. These results corroborate the view that cortical horizontal connections have a central role in functional reorganization, as revealed here by progressive facilitation of synaptic activity and the traveling wave of excitation that propagates horizontally into the deprived cortical region.}, Author = {Palagina, Ganna and Eysel, Ulf T and Jancke, Dirk}, Date-Added = {2011-03-17 15:32:55 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Sensory Deprivation;neurological disorder;structural remodeling;experience dependent plasticity;optical physiology;optical imaging;voltage sensor;in vivo;microscopy;technique;21 Neurophysiology}, Mesh = {Aging; Animals; Coloring Agents; Electrophysiological Phenomena; Rats; Retina; Visual Cortex}, Month = {May}, Number = {21}, Pages = {8743-7}, Pmc = {PMC2689012}, pmid = {19420221}, Pst = {ppublish}, Title = {Strengthening of lateral activation in adult rat visual cortex after retinal lesions captured with voltage-sensitive dye imaging in vivo}, Volume = {106}, Year = {2009}, url = {papers/Palagina_ProcNatlAcadSciUSA2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0900068106}} @article{Tritsch:2010, Abstract = {Neurons in the developing auditory system fire bursts of action potentials before the onset of hearing. This spontaneous activity promotes the survival and maturation of auditory neurons and the refinement of synaptic connections in auditory nuclei; however, the mechanisms responsible for initiating this activity remain uncertain. Previous studies indicate that inner supporting cells (ISCs) in the developing cochlea periodically release ATP, which depolarizes inner hair cells (IHCs), leading to bursts of action potentials in postsynaptic spiral ganglion neurons (SGNs). To determine when purinergic signaling appears in the developing cochlea and whether it is responsible for initiating auditory neuron activity throughout the prehearing period, we examined spontaneous activity from ISCs, IHCs, and SGNs in cochleae acutely isolated from rats during the first three postnatal weeks. We found that ATP was released from ISCs within the cochlea from birth until the onset of hearing, which led to periodic inward currents, Ca(2+) transients, and morphological changes in these supporting cells. This spontaneous release of ATP also depolarized IHCs and triggered bursts of action potentials in SGNs for most of the postnatal prehearing period, beginning a few days after birth as IHCs became responsive to ATP, until the onset of hearing when ATP was no longer released from ISCs. When IHCs were not subject to purinergic excitation, SGNs exhibited little or no activity. These results suggest that supporting cells in the cochlea provide the primary excitatory stimulus responsible for initiating bursts of action potentials in auditory nerve fibers before the onset of hearing.}, Author = {Tritsch, Nicolas X and Bergles, Dwight E}, Date-Added = {2011-03-17 15:29:45 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;Spontaneous activity;Cochlear Nerve;Auditory Pathways;Electrophysiology;21 Neurophysiology;Calcium Channels}, Mesh = {Action Potentials; Adenosine Triphosphate; Animals; Animals, Newborn; Cell Differentiation; Cochlea; Hair Cells, Auditory; Hair Cells, Auditory, Inner; Hearing; Labyrinth Supporting Cells; Organogenesis; Rats; Rats, Sprague-Dawley; Sensory Receptor Cells; Spiral Ganglion}, Month = {Jan}, Number = {4}, Pages = {1539-50}, Pmc = {PMC2814371}, pmid = {20107081}, Pst = {ppublish}, Title = {Developmental regulation of spontaneous activity in the Mammalian cochlea}, Volume = {30}, Year = {2010}, url = {papers/Tritsch_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3875-09.2010}} @article{Kotak:1995, Abstract = {1. Although synaptic transmission is known to influence many aspects of neuronal development, activity rates are quite low at early ages. The present study describes a long-lasting postsynaptic response to brief periods of synaptic stimulation that may underlie such an influence. Whole-cell patch clamp recordings were made from the lateral superior olive (LSO) in a brain slice preparation from early postnatal gerbils. 2. Stimulation of the excitatory afferent pathway from the cochlear nucleus elicited a prolonged depolarization (PD) in approximately 60\% of the LSO neurons tested. Low frequency stimulation (1 Hz) was as effective as tetanic stimulation in producing PDs. These synaptically evoked depolarizations ranged in amplitude from 3 to 32 mV and recovered spontaneously after 0.5-35 min. 3. The LSO neuron input resistance declined during every PD episode and remained significantly lower even after the membrane potential had recovered. These PDs were partially reversed by 2 mM Ni(+2), but 1 microM tetrodotoxin and 10 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were ineffective. The metabotropic glutamate receptor agonist, trans-1-aminocyclopentane-1,3-dicarboxylic acid (40 microM), produced depolarizations that outlasted the exposure period by an average of 20 min and were also partially repolarized by 2 mM Ni(+2). In contrast, the depolarizations produced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid or N-methyl-D-aspartate decayed within a much shorter period of time. 4. To test whether in vivo discharge rates are, in fact, very low during development, spontaneous activity was recorded from neurons of the auditory midbrain in gerbils before and during the onset of sound-evoked responses. The average discharge rate of auditory neurons was quite low (X = 0.4 spikes/s), although many cells displayed brief periods of rapid discharge rate (X = 37 spikes/ s). Together, these results demonstrate a novel form of developmental plasticity elicited by low rates of glutamatergic transmission that may involve a metabotropic pathway and prolonged calcium influx.}, Author = {Kotak, V C and Sanes, D H}, Date-Added = {2011-03-17 15:26:53 -0400}, Date-Modified = {2011-03-17 15:28:02 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {21 Activity-development;Spontaneous activity;plasticity;structural remodeling;axons;refinement;tonotopy;brain stem;Auditory Pathways;Electrophysiology;21 Neurophysiology}, Mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione; Aging; Animals; Animals, Newborn; Auditory Pathways; Electrophysiology; Excitatory Amino Acid Agonists; Excitatory Amino Acid Antagonists; Gerbillinae; Nickel; Reaction Time; Synapses; Tetrodotoxin}, Month = {Oct}, Number = {4}, Pages = {1611-20}, pmid = {8989397}, Pst = {ppublish}, Title = {Synaptically evoked prolonged depolarizations in the developing auditory system}, Volume = {74}, Year = {1995}, url = {papers/Kotak_JNeurophysiol1995.pdf}} @article{Kandler:2009, Abstract = {A fundamental organizing principle of auditory brain circuits is tonotopy, the orderly representation of the sound frequency to which neurons are most sensitive. Tonotopy arises from the coding of frequency along the cochlea and the topographic organization of auditory pathways. The mechanisms that underlie the establishment of tonotopy are poorly understood. In auditory brainstem pathways, topographic precision is present at very early stages in development, which may suggest that synaptic reorganization contributes little to the construction of precise tonotopic maps. Accumulating evidence from several brainstem nuclei, however, is now changing this view by demonstrating that developing auditory brainstem circuits undergo a marked degree of refinement on both a subcellular and circuit level.}, Author = {Kandler, Karl and Clause, Amanda and Noh, Jihyun}, Date-Added = {2011-03-17 14:54:13 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Activity-development;circuit formation;Brain Stem;Auditory Pathways;Cochlear Nerve;tonotopy;Spontaneous activity;structural remodeling;refinement;axons;review}, Mesh = {Animals; Auditory Pathways; Axons; Brain Stem; Cochlea; Humans; Neuronal Plasticity; Olivary Nucleus; Pitch Perception}, Month = {Jun}, Number = {6}, Pages = {711-7}, Pmc = {PMC2780022}, pmid = {19471270}, Pst = {ppublish}, Title = {Tonotopic reorganization of developing auditory brainstem circuits}, Volume = {12}, Year = {2009}, url = {papers/Kandler_NatNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2332}} @article{Enquist:2003, Abstract = {In the past decade, the literature describing how viruses can be used to define the synaptic architecture of the brain has increased dramatically. Early studies focused on determining the specificity of viral transport through synaptic connections. Analysis of the assembly and intracellular transport of viruses as well as of the role of the brain response to infection were central to this literature. With the growing acceptance that the transport of viruses is circuit-related, attention has shifted to application of the method to define the functional architecture of neural systems. The development of attenuated recombinant viruses that maintain neuroinvasiveness has been instrumental to the generation of increasingly powerful experimental approaches for the functional dissection of neural circuits. These approaches include the use of recombinant viruses that express unique reporters to address issues of axon collateralization in complex circuits, the use of green-fluorescent-protein-expressing recombinants to characterize the electrophysiological properties of projection-specific neurons in live slices of brain, and the exploitation of the Cre recombinase system for conditional replication of virus in phenotypically defined populations of neurons.}, Author = {Enquist, Lynn W and Card, J Patrick}, Date-Added = {2011-03-17 14:50:19 -0400}, Date-Modified = {2011-03-17 14:53:13 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Trans-synaptic;Technique;review;Anatomy;Viral Envelope Proteins;Virus;viral gene transfer;connectivity;synapses;frontiers review}, Mesh = {Animals; Brain; Herpesvirus 1, Suid; Humans; Nerve Net; Virus Replication}, Month = {Oct}, Number = {5}, Pages = {603-6}, pmid = {14630225}, Pst = {ppublish}, Title = {Recent advances in the use of neurotropic viruses for circuit analysis}, Volume = {13}, Year = {2003}, url = {papers/Enquist_CurrOpinNeurobiol2003.pdf}} @article{Card:2011, Abstract = {Transneuronal transport of neurotropic viruses is widely used to define the organization of neural circuitry in the mature and developing nervous system. However, interconnectivity within complex circuits limits the ability of viral tracing to define connections specifically linked to a subpopulation of neurons within a network. Here we demonstrate a unique viral tracing technology that highlights connections to defined populations of neurons within a larger labeled network. This technology was accomplished by constructing a replication-competent strain of pseudorabies virus (PRV-263) that changes the profile of fluorescent reporter expression in the presence of Cre recombinase (Cre). The viral genome carries a Brainbow cassette that expresses a default red reporter in infected cells. However, in the presence of Cre, the red reporter gene is excised from the genome and expression of yellow or cyan reporters is enabled. We used PRV-263 in combination with a unique lentivirus vector that produces Cre expression in catecholamine neurons. Projection-specific infection of central circuits containing these Cre-expressing catecholamine neurons with PRV-263 resulted in Cre-mediated recombination of the PRV-263 genome and conditional expression of cyan/yellow reporters. Replication and transneuronal transport of recombined virus produced conditional reporter expression in neurons synaptically linked to the Cre-expressing catecholamine neurons. This unique technology highlights connections specific to phenotypically defined neurons within larger networks infected by retrograde transneuronal transport of virus from a defined projection target. The availability of other technologies that restrict Cre expression to defined populations of neurons indicates that this approach can be widely applied across functionally defined systems.}, Author = {Card, J Patrick and Kobiler, Oren and McCambridge, Joshua and Ebdlahad, Sommer and Shan, Zhiying and Raizada, Mohan K and Sved, Alan F and Enquist, Lynn W}, Date-Added = {2011-03-17 13:19:52 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Technique;Trans-synaptic;viral gene transfer;Virus;Viral Envelope Proteins;fluorescent proteins;Transgenic;mouse;mice;connectivity;synapses;frontiers review}, Month = {Feb}, Number = {8}, Pages = {3377-82}, Pmc = {PMC3044368}, pmid = {21292985}, Pst = {ppublish}, Title = {Microdissection of neural networks by conditional reporter expression from a Brainbow herpesvirus}, Volume = {108}, Year = {2011}, url = {papers/Card_ProcNatlAcadSciUSA2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1015033108}} @article{Bock:2011, Abstract = {In the cerebral cortex, local circuits consist of tens of thousands of neurons, each of which makes thousands of synaptic connections. Perhaps the biggest impediment to understanding these networks is that we have no wiring diagrams of their interconnections. Even if we had a partial or complete wiring diagram, however, understanding the network would also require information about each neuron's function. Here we show that the relationship between structure and function can be studied in the cortex with a combination of in vivo physiology and network anatomy. We used two-photon calcium imaging to characterize a functional property--the preferred stimulus orientation--of a group of neurons in the mouse primary visual cortex. Large-scale electron microscopy of serial thin sections was then used to trace a portion of these neurons' local network. Consistent with a prediction from recent physiological experiments, inhibitory interneurons received convergent anatomical input from nearby excitatory neurons with a broad range of preferred orientations, although weak biases could not be rejected.}, Author = {Bock, Davi D and Lee, Wei-Chung Allen and Kerlin, Aaron M and Andermann, Mark L and Hood, Greg and Wetzel, Arthur W and Yurgenson, Sergey and Soucy, Edward R and Kim, Hyon Suk and Reid, R Clay}, Date-Added = {2011-03-17 13:12:50 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology;optical imaging;calcium imaging;Anatomy;connectivity;connectome;Circuit structure-function;Neocortex;visual cortex;in vivo;electron microscopy;Synapses;frontiers review}, Month = {Mar}, Number = {7337}, Pages = {177-82}, pmid = {21390124}, Pst = {ppublish}, Title = {Network anatomy and in vivo physiology of visual cortical neurons}, Volume = {471}, Year = {2011}, url = {papers/Bock_Nature2011.pdf}, Bdsk-File-2 = {papers/Bock_Nature2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature09802}} @article{Adams:2009, Abstract = {Consolidation of synaptic plasticity seems to require transcription, but how the nucleus is informed in this context remains unknown. As NMDA receptor antagonists have been shown to interfere with action potential generation, the issue of whether or not a synaptically generated signal is required for nuclear signaling is currently unresolved. Here, we show that pharmacological maintenance of action potentials during NMDA receptor blockade allows for NMDA receptor-independent transcription factor binding and arc gene expression, both of which were previously thought to be NMDA receptor dependent. These data suggest that types of signaling in the nucleus previously attributed to NMDA-receptor-dependent synapse-to-nucleus signals can be initiated in the absence of NMDA receptor-dependent synaptic plasticity.}, Author = {Adams, J Paige and Robinson, Rachel A and Hudgins, Eric D and Wissink, Erin M and Dudek, Serena M}, Date-Added = {2011-03-17 13:09:36 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuroreport}, Journal-Full = {Neuroreport}, Keywords = {21 Activity-development;experience dependent plasticity;Long-Term Potentiation;Immediate-Early;genes;Electrophysiology;21 Neurophysiology;N-Methyl-D-Aspartate}, Mesh = {2-Amino-5-phosphonovalerate; Animals; Bicuculline; Biophysics; Electric Stimulation; Electrophoretic Mobility Shift Assay; Excitatory Amino Acid Antagonists; GABA Antagonists; Gene Expression Regulation; Hippocampus; Long-Term Potentiation; Nuclear Proteins; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Transcription Factors}, Month = {Oct}, Number = {16}, Pages = {1429-33}, Pmc = {PMC2766847}, pmid = {19794318}, Pst = {ppublish}, Title = {NMDA receptor-independent control of transcription factors and gene expression}, Volume = {20}, Year = {2009}, url = {papers/Adams_Neuroreport2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1097/WNR.0b013e3283311db6}} @article{Yashiro:2009, Abstract = {Experience-dependent maturation of neocortical circuits is required for normal sensory and cognitive abilities, which are distorted in neurodevelopmental disorders. We tested whether experience-dependent neocortical modifications require Ube3a, an E3 ubiquitin ligase whose dysregulation has been implicated in autism and Angelman syndrome. Using visual cortex as a model, we found that experience-dependent maturation of excitatory cortical circuits was severely impaired in Angelman syndrome model mice deficient in Ube3a. This developmental defect was associated with profound impairments in neocortical plasticity. Normal plasticity was preserved under conditions of sensory deprivation, but was rapidly lost by sensory experiences. The loss of neocortical plasticity is reversible, as late-onset visual deprivation restored normal synaptic plasticity. Furthermore, Ube3a-deficient mice lacked ocular dominance plasticity in vivo when challenged with monocular deprivation. We conclude that Ube3a is necessary for maintaining plasticity during experience-dependent neocortical development and suggest that the loss of neocortical plasticity contributes to deficits associated with Angelman syndrome.}, Author = {Yashiro, Koji and Riday, Thorfinn T and Condon, Kathryn H and Roberts, Adam C and Bernardo, Danilo R and Prakash, Rohit and Weinberg, Richard J and Ehlers, Michael D and Philpot, Benjamin D}, Date-Added = {2011-03-17 13:03:56 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Immediate-Early;genes;21 Activity-development;circuit formation;experience dependent plasticity;Sensory Deprivation;visual cortex;visual system;structural remodeling;Critical Period;mouse;mice;Transgenic;development;frontiers review}, Mesh = {Aging; Angelman Syndrome; Animals; Animals, Newborn; Cell Differentiation; Disease Models, Animal; Dominance, Ocular; Learning; Mice; Mice, Knockout; Neocortex; Neuronal Plasticity; Sensory Deprivation; Ubiquitin-Protein Ligases; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Jun}, Number = {6}, Pages = {777-83}, Pmc = {PMC2741303}, pmid = {19430469}, Pst = {ppublish}, Title = {Ube3a is required for experience-dependent maturation of the neocortex}, Volume = {12}, Year = {2009}, url = {papers/Yashiro_NatNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2327}} @article{Shepherd:2011, Abstract = {Many proteins have been implicated in synaptic and experience-dependent plasticity. However, few demonstrate the exquisite regulation of expression and breadth of functional importance as the immediate early gene product Arc. Here we review and attempt to synthesize the disparate views of Arc in neuronal function. The main conclusion garnered from this body of work is that Arc is a critical effector molecule downstream of many molecular signaling pathways and that dysregulation of Arc expression can have dire consequences for normal brain function.}, Author = {Shepherd, Jason D and Bear, Mark F}, Date-Added = {2011-03-17 12:55:08 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Immediate-Early;genes;review;21 Activity-development;experience dependent plasticity;homeostatic plasticity;Long-Term Potentiation;Long-Term Synaptic Depression;synapse formation}, Month = {Mar}, Number = {3}, Pages = {279-84}, pmid = {21278731}, Pst = {ppublish}, Title = {New views of Arc, a master regulator of synaptic plasticity}, Volume = {14}, Year = {2011}, url = {papers/Shepherd_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2708}} @article{Lodato:2011, Abstract = {In the mammalian cerebral cortex, the developmental events governing the integration of excitatory projection neurons and inhibitory interneurons into balanced local circuitry are poorly understood. We report that different subtypes of projection neurons uniquely and differentially determine the laminar distribution of cortical interneurons. We find that in Fezf2(-/-) cortex, the exclusive absence of subcerebral projection neurons and their replacement by callosal projection neurons cause distinctly abnormal lamination of interneurons and altered GABAergic inhibition. In addition, experimental generation of either corticofugal neurons or callosal neurons below the cortex is sufficient to recruit cortical interneurons to these ectopic locations. Strikingly, the identity of the projection neurons generated, rather than strictly their birthdate, determines the specific types of interneurons recruited. These data demonstrate that in the neocortex individual populations of projection neurons cell-extrinsically control the laminar fate of interneurons and the assembly of local inhibitory circuitry.}, Author = {Lodato, Simona and Rouaux, Caroline and Quast, Kathleen B and Jantrachotechatchawan, Chanati and Studer, Mich{\`e}le and Hensch, Takao K and Arlotta, Paola}, Date-Added = {2011-03-17 12:50:23 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {circuit formation;development;Circuit structure-function;Pyramidal Cells;Interneurons;cell migration;Neocortex;GABA;genes;Transgenic;mice;mouse;lamination;dysplasia;heterotopic;doublecortin}, Month = {Feb}, Number = {4}, Pages = {763-79}, pmid = {21338885}, Pst = {ppublish}, Title = {Excitatory projection neuron subtypes control the distribution of local inhibitory interneurons in the cerebral cortex}, Volume = {69}, Year = {2011}, url = {papers/Lodato_Neuron2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2011.01.015}} @article{Otsuka:2011, Abstract = {Recent advances have established that intralaminar and interlaminar excitatory networks between neocortical pyramidal cells are specialized into subnetworks. Here, we have investigated how the commissural system organizes the intracortical excitatory subnetworks to communicate between cortical hemispheres. Whole-cell recordings were obtained from callosal projection neurons [commissural (COM) cells], identified by in vivo injection of retrograde fluorescent tracer into one hemisphere, in rat frontal cortical slices. We found that layer V (L5) COM cells were heterogeneous in physiological and morphological properties that correlated with projection patterns to contralateral and ipsilateral cortical areas. The probability of synaptically connected pairs of L5 COM cells was higher in cell pairs of the same firing subtypes than that in different cell subtype pairs. In interlaminar connections, layer II/III (L2/3) COM cells preferentially innervated L5 COM cells. Moreover, pairs of the same L5 COM subtypes were more likely to share inputs from L2/3 COM cells than were different COM subtype cell pairs. In addition, common inputs from L2/3 COM cells were frequently observed in L5 pairs of corticopontine cells and given firing subtypes of COM cells. Our results suggest that callosal communications are achieved via several distinct COM cell subnetworks differentiated according to the ipsilateral corticocortical and subcortical projection patterns.}, Author = {Otsuka, Takeshi and Kawaguchi, Yasuo}, Date-Added = {2011-03-17 12:46:15 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Circuit structure-function;connectivity;Neocortex;Synapses;Electrophysiology;in vitro;21 Neurophysiology;Anatomy}, Month = {Mar}, Number = {10}, Pages = {3862-70}, pmid = {21389241}, Pst = {ppublish}, Title = {Cell Diversity and Connection Specificity between Callosal Projection Neurons in the Frontal Cortex}, Volume = {31}, Year = {2011}, url = {papers/Otsuka_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5795-10.2011}} @article{Briggman:2011, Abstract = {The proper connectivity between neurons is essential for the implementation of the algorithms used in neural computations, such as the detection of directed motion by the retina. The analysis of neuronal connectivity is possible with electron microscopy, but technological limitations have impeded the acquisition of high-resolution data on a large enough scale. Here we show, using serial block-face electron microscopy and two-photon calcium imaging, that the dendrites of mouse starburst amacrine cells make highly specific synapses with direction-selective ganglion cells depending on the ganglion cell's preferred direction. Our findings indicate that a structural (wiring) asymmetry contributes to the computation of direction selectivity. The nature of this asymmetry supports some models of direction selectivity and rules out others. It also puts constraints on the developmental mechanisms behind the formation of synaptic connections. Our study demonstrates how otherwise intractable neurobiological questions can be addressed by combining functional imaging with the analysis of neuronal connectivity using large-scale electron microscopy.}, Author = {Briggman, Kevin L and Helmstaedter, Moritz and Denk, Winfried}, Date-Added = {2011-03-17 12:38:20 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical imaging;optical physiology;microscopy;Technique;connectivity;connectome;Circuit structure-function;Retina;Computational Biology;Anatomy;multiphoton;calcium imaging;frontiers review}, Month = {Mar}, Number = {7337}, Pages = {183-8}, pmid = {21390125}, Pst = {ppublish}, Title = {Wiring specificity in the direction-selectivity circuit of the retina}, Volume = {471}, Year = {2011}, url = {papers/Briggman_Nature2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature09818}} @article{Lebrun-Julien:2009, Abstract = {The central hypothesis of excitotoxicity is that excessive stimulation of neuronal NMDA-sensitive glutamate receptors is harmful to neurons and contributes to a variety of neurological disorders. Glial cells have been proposed to participate in excitotoxic neuronal loss, but their precise role is defined poorly. In this in vivo study, we show that NMDA induces profound nuclear factor kappaB (NF-kappaB) activation in M{\"u}ller glia but not in retinal neurons. Intriguingly, NMDA-induced death of retinal neurons is effectively blocked by inhibitors of NF-kappaB activity. We demonstrate that tumor necrosis factor alpha (TNFalpha) protein produced in M{\"u}ller glial cells via an NMDA-induced NF-kappaB-dependent pathway plays a crucial role in excitotoxic loss of retinal neurons. This cell loss occurs mainly through a TNFalpha-dependent increase in Ca(2+)-permeable AMPA receptors on susceptible neurons. Thus, our data reveal a novel non-cell-autonomous mechanism by which glial cells can profoundly exacerbate neuronal death following excitotoxic injury.}, Author = {Lebrun-Julien, Fr{\'e}d{\'e}ric and Duplan, Laure and Pernet, Vincent and Osswald, Ingrid and Sapieha, Przemyslaw and Bourgeois, Philippe and Dickson, Kathleen and Bowie, Derek and Barker, Philip A and Di Polo, Adriana}, Date-Added = {2011-03-17 12:35:48 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;Apoptosis;Cell Adhesion;neuron;glia;macrophage;Retina;development;excitotoxcity;Competitive Behavior;cell interaction;evolutionary dynamics;genes}, Mesh = {Animals; Cell Death; Cell Survival; Excitatory Amino Acid Agonists; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; N-Methylaspartate; Retinal Neurons; Tumor Necrosis Factor-alpha}, Month = {Apr}, Number = {17}, Pages = {5536-45}, pmid = {19403821}, Pst = {ppublish}, Title = {Excitotoxic death of retinal neurons in vivo occurs via a non-cell-autonomous mechanism}, Volume = {29}, Year = {2009}, url = {papers/Lebrun-Julien_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0831-09.2009}} @article{Wilhelm:2009, Abstract = {When neuronal activity is reduced over a period of days, compensatory changes in synaptic strength and/or cellular excitability are triggered, which are thought to act in a manner to homeostatically recover normal activity levels. The time course over which changes in homeostatic synaptic strength and cellular excitability occur are not clear. Although many studies show that 1-2 days of activity block are necessary to trigger increases in excitatory quantal strength, few studies have been able to examine whether these mechanisms actually underlie recovery of network activity. Here, we examine the mechanisms underlying recovery of embryonic motor activity following block of either excitatory GABAergic or glutamatergic inputs in vivo. We find that GABA(A) receptor blockade triggers fast changes in cellular excitability that occur during the recovery of activity but before changes in synaptic scaling. This increase in cellular excitability is mediated in part by an increase in sodium currents and a reduction in the fast-inactivating and calcium-activated potassium currents. These findings suggest that compensatory changes in cellular excitability, rather than synaptic scaling, contribute to activity recovery. Further, we find a special role for the GABA(A) receptor in triggering several homeostatic mechanisms after activity perturbations, including changes in cellular excitability and GABAergic and AMPAergic synaptic strength. The temporal difference in expression of homeostatic changes in cellular excitability and synaptic strength suggests that there are multiple mechanisms and pathways engaged to regulate network activity, and that each may have temporally distinct functions.}, Author = {Wilhelm, Jennifer C and Rich, Mark M and Wenner, Peter}, Date-Added = {2011-03-17 12:24:43 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Activity-development;synapse formation;experience dependent plasticity;homeostatic plasticity;synaptic scaling;Electrophysiology;Spinal Cord;Spontaneous activity;21 Neurophysiology}, Mesh = {Animals; Calcium Channels; Chick Embryo; GABA-A Receptor Antagonists; Homeostasis; Ion Channel Gating; Nerve Net; Neurons; Pyridazines; Sodium Channels; Synapses; Time Factors}, Month = {Apr}, Number = {16}, Pages = {6760-5}, Pmc = {PMC2672480}, pmid = {19346492}, Pst = {ppublish}, Title = {Compensatory changes in cellular excitability, not synaptic scaling, contribute to homeostatic recovery of embryonic network activity}, Volume = {106}, Year = {2009}, url = {papers/Wilhelm_ProcNatlAcadSciUSA2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0813058106}} @article{Mitchell:2009, Abstract = {The accurate representation of the motion of external objects is one of the more important tasks of the visual areas of the brain because motion by itself can provide sufficient information for discriminating visual forms and hence breaking camouflage. Whereas the analysis of the motion of single small elements can occur in primary visual cortex (V1), the perception of a common direction of global motion of some visual elements among many is supported by extrastriate cortical areas [1, 2]. Humans treated for binocular congenital cataracts afterward exhibit extreme deficits of global motion, but after monocular cataracts, the deficits are minimal [3]. These observations suggest a need for normal early patterned visual experience through at least one eye for global motion perception to develop in a typical fashion. We investigated this role for early experience and its timing on kittens that were deprived of light or patterned light at different ages. Such deprivation in the first 6 weeks resulted in long-lasting (>2 yr) profound deficits of perception of global motion but no apparent effects on the perception of simple unidirectional motion. Contrary to current opinion, sensitive periods to visual deprivation in primary and extrastriate cortex may be of similar duration.}, Author = {Mitchell, Donald E and Kennie, Jan and Kung, Diane}, Date-Added = {2011-03-17 12:06:46 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {visual system;Neocortex;visual cortex;Superior Colliculus;neurological disorder;development;21 Activity-development;circuit formation;function;Behavior;Motion Perception;human;cat;Sensory Deprivation;Binocular}, Mesh = {Animals; Animals, Newborn; Behavior, Animal; Cats; Humans; Light; Motion Perception; Photic Stimulation; Sensory Deprivation; Vision, Binocular; Visual Pathways}, Month = {Apr}, Number = {8}, Pages = {645-9}, pmid = {19285405}, Pst = {ppublish}, Title = {Development of global motion perception requires early postnatal exposure to patterned light}, Volume = {19}, Year = {2009}, url = {papers/Mitchell_CurrBiol2009.pdf}, Bdsk-File-2 = {papers/Mitchell_CurrBiol2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2009.02.038}} @article{Kaku:2009, Abstract = {Vital to motor learning is information about movement error. Using this information, the brain creates neural learning signals that instruct a plasticity mechanism to produce appropriate behavioral learning. Little is known, however, about brain structures that generate learning signals for voluntary movements. Here we show that signals from the superior colliculus (SC) can drive learning in saccadic eye movements in the monkey. Electrical stimulation of the SC deeper layers, subthreshold for evoking saccades, was applied immediately (approximately 60 ms) after the end of horizontal saccades in one or both directions. The target disappeared during saccades and remained invisible for 1 s to eliminate effects of postsaccadic visual information. Repetitive pairing of saccades with SC stimulation produced a marked, two-dimensional shift in movement endpoint relative to the target location. The elicited endpoint shift took a gradual, approximately exponential course over several hundred saccades as in visually induced saccade adaptation. The shift in movement endpoint remained nearly unchanged after stimulation was discontinued, indicating involvement of neuronal plasticity. When both rightward and leftward saccades were paired with stimulation, their endpoints shifted in similar directions. The endpoint shift was directed contralaterally to the stimulated SC. The direction and size of the endpoint shift depended on the stimulation site in the SC. We propose that the SC, a brainstem structure long known to be crucial for saccade execution, is involved in motor learning and sends signals that dictate the direction of adaptive shift in saccade endpoint.}, Author = {Kaku, Yuki and Yoshida, Kaoru and Iwamoto, Yoshiki}, Date-Added = {2011-03-17 12:05:36 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Superior Colliculus;optic tectum;function;Behavior;monkey;Saccades;visual system;experience dependent plasticity;entrainment}, Mesh = {Adaptation, Physiological; Animals; Learning; Macaca mulatta; Male; Photic Stimulation; Saccades; Superior Colliculi}, Month = {Apr}, Number = {16}, Pages = {5266-75}, pmid = {19386923}, Pst = {ppublish}, Title = {Learning signals from the superior colliculus for adaptation of saccadic eye movements in the monkey}, Volume = {29}, Year = {2009}, url = {papers/Kaku_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0661-09.2009}} @article{Bollmann:2009, Abstract = {Neural pathways projecting from sensory organs to higher brain centers form topographic maps in which neighbor relationships are preserved from a sending to a receiving neural population. Sensory input can generate compartmentalized electrical and biochemical activity in the dendrites of a receiving neuron. Here, we show that in the developing retinotectal projection of young Xenopus tadpoles, visually driven Ca2+ signals are topographically organized at the subcellular, dendritic scale. Functional in vivo two-photon Ca2+ imaging revealed that the sensitivity of dendritic Ca2+ signals to stimulus location in visual space is correlated with their anatomical position within the dendritic tree of individual neurons. This topographic distribution was dependent on NMDAR activation, whereas global Ca2+ signals were mediated by Ca2+ influx through dendritic, voltage-dependent Ca2+ channels. These findings suggest a framework for plasticity models that invoke local dendritic Ca2+ signaling in the elaboration of neural connectivity and dendrite-specific information storage.}, Author = {Bollmann, Johann H and Engert, Florian}, Date-Added = {2011-03-17 12:02:42 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;visual system;optic tectum;Zebrafish;in vivo;Electrophysiology;calcium imaging;optical physiology;optical imaging;function;Circuit structure-function;Calcium Channels;plasticity;experience dependent plasticity;multiphoton;microscopy}, Mesh = {Action Potentials; Animals; Brain Mapping; Calcium; Calcium Signaling; Dendrites; Excitatory Amino Acid Antagonists; GABA Antagonists; Imaging, Three-Dimensional; Larva; Light; Microscopy, Confocal; Neurons; Photic Stimulation; Presynaptic Terminals; Pyridazines; Receptors, N-Methyl-D-Aspartate; Subcellular Fractions; Valine; Visual Pathways; Xenopus}, Month = {Mar}, Number = {6}, Pages = {895-905}, Pmc = {PMC2892759}, pmid = {19323998}, Pst = {ppublish}, Title = {Subcellular topography of visually driven dendritic activity in the vertebrate visual system}, Volume = {61}, Year = {2009}, url = {papers/Bollmann_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.01.018}} @article{Brown:2009, Abstract = {After brain damage such as stroke, topographically organized sensory and motor cortical representations remap onto adjacent surviving tissues. It is conceivable that cortical remapping is accomplished by changes in the temporal precision of sensory processing and regional connectivity in the cortex. To understand how the adult cortex remaps and processes sensory signals during stroke recovery, we performed in vivo imaging of sensory-evoked changes in membrane potential, as well as multiphoton imaging of dendrite structure and tract tracing. In control mice, forelimb stimulation evoked a brief depolarization in forelimb cortex that quickly propagated to, and dissipated within, adjacent motor/hindlimb areas (<100 ms). One week after forelimb cortex stroke, the cortex was virtually unresponsive to tactile forelimb stimulation. After 8 weeks recovery, forelimb-evoked depolarizations reemerged with a characteristic pattern in which responses began within surviving portions of forelimb cortex (<20 ms after stimulation) and then spread horizontally into neighboring peri-infarct motor/hindlimb areas in which depolarization persisted 300-400\% longer than controls. These uncharacteristically prolonged responses were not limited to the remapped peri-infarct zone and included distant posteromedial retrosplenial cortex, millimeters from the stroke. Structurally, the remapped peri-infarct area selectively exhibited high levels of dendritic spine turnover, shared more connections with retrosplenial cortex and striatum, and lost inputs from lateral somatosensory cortical regions. Our findings demonstrate that sensory remapping during stroke recovery is accompanied by the development of prolonged sensory responses and new structural circuits in both the peri-infarct zone as well as more distant sites.}, Author = {Brown, Craig E and Aminoltejari, Khatereh and Erb, Heidi and Winship, Ian R and Murphy, Timothy H}, Date-Added = {2011-03-17 11:43:36 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {neurological disorder;Stroke;Neocortex;Somatosensory Cortex;optical physiology;optical imaging;voltage sensor;Imaging;in vivo;structural remodeling;plasticity;Mouse;mice;Transgenic}, Mesh = {Animals; Brain Mapping; Cerebral Infarction; Fluorescent Dyes; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Neuronal Plasticity; Photic Stimulation; Rose Bengal; Somatosensory Cortex; Time Factors}, Month = {Feb}, Number = {6}, Pages = {1719-34}, pmid = {19211879}, Pst = {ppublish}, Title = {In vivo voltage-sensitive dye imaging in adult mice reveals that somatosensory maps lost to stroke are replaced over weeks by new structural and functional circuits with prolonged modes of activation within both the peri-infarct zone and distant sites}, Volume = {29}, Year = {2009}, url = {papers/Brown_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4249-08.2009}} @article{Marrone:2008, Abstract = {Immediate-early genes (IEGs) are tightly coupled to cellular activity and play a critical role in regulating synaptic plasticity. While encoding spatial experience, hippocampal principal cells express IEGs in a behaviorally dependent and cell-specific manner. This expression can be detected through the use of cellular compartment analysis of temporal activity by fluorescence in situ hybridization to generate estimates of cellular activity that match direct neuronal recording under comparable conditions. During rest, IEG expression continues to occur in a small number of cells, and the role of this basal expression is unknown. Imaging IEGs expressed during exploration and adjacent rest periods reveals that "constitutive" IEG expression during rest is not random. Rather, consistent with proposed memory consolidation mechanisms, it recapitulates a subset of the pattern generated by recent experience.}, Author = {Marrone, Diano F and Schaner, Michael J and McNaughton, Bruce L and Worley, Paul F and Barnes, Carol A}, Date-Added = {2011-03-17 11:40:53 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;circuit formation;Circuit structure-function;experience dependent plasticity;Iminmediate-Early;genes;Hippocampus;function;Behavior;Imaging;Technique;microscopy;optical physiology;optical imaging;frontiers review}, Mesh = {Animals; Carrier Proteins; Exploratory Behavior; Gene Expression Regulation; Genes, Immediate-Early; Learning; Rats; Rats, Inbred F344; Rest; Time Factors}, Month = {Jan}, Number = {5}, Pages = {1030-3}, pmid = {18234881}, Pst = {ppublish}, Title = {Immediate-early gene expression at rest recapitulates recent experience}, Volume = {28}, Year = {2008}, url = {papers/Marrone_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4235-07.2008}} @article{Guzowski:1999, Abstract = {We used fluorescent in-situ hybridization and confocal microscopy to monitor the subcellular distribution of the immediate-early gene Arc. Arc RNA appeared in discrete intranuclear foci within minutes of neuronal activation and subsequently disappeared from the nucleus and accumulated in the cytoplasm by 30 minutes. The time course of nuclear versus cytoplasmic Arc RNA accumulation was distinct, and could therefore be used to infer the activity history of individual neurons at two times. Following sequential exposure of rats to two different environments or to the same environment twice, the proportion of CA1 neurons with cytoplasmic, nuclear or overlapping Arc expression profiles matched predictions derived from ensemble neurophysiological recordings of hippocampal neuronal ensembles. Arc gene induction is thus specifically linked to neural encoding processes.}, Author = {Guzowski, J F and McNaughton, B L and Barnes, C A and Worley, P F}, Date-Added = {2011-03-17 11:37:35 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Activity-development;Immediate-Early;genes;circuit formation;Circuit structure-function;experience dependent plasticity;Imaging;Technique;optical physiology;optical imaging;Hippocampus;frontiers review}, Mesh = {Animals; Cell Nucleus; Cytoplasm; Cytoskeletal Proteins; Dendrites; Electroshock; Gene Expression Profiling; Gene Expression Regulation; Genes, Immediate-Early; Handling (Psychology); Hippocampus; Housing, Animal; In Situ Hybridization, Fluorescence; Male; Microscopy, Confocal; Nerve Tissue Proteins; Neurons; RNA Probes; RNA Stability; RNA, Messenger; Rats; Rats, Inbred F344; Time Factors; Transcriptional Activation}, Month = {Dec}, Number = {12}, Pages = {1120-4}, pmid = {10570490}, Pst = {ppublish}, Title = {Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles}, Volume = {2}, Year = {1999}, url = {papers/Guzowski_NatNeurosci1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/16046}} @article{Guzowski:2005, Abstract = {Immediate-early genes have gained widespread popularity as activity markers for mapping neuronal circuits involved in specific behaviors in many different species. In situ immediate early gene detection methods provide cellular level resolution, a major benefit for mapping neuronal networks. Recent advances using fluorescence in situ hybridization also afford temporal resolution, enabling within-animal activity maps for two distinct behaviors. Moreover, use of transgenic mice with fluorescent reporter proteins driven by immediate early gene promoters is enabling repeated measurements, over long time scales, of cortical activity within the same animal. These methodological innovations, coupled with recent advances in fluorescence imaging and probe development, will enable large scale mapping of behaviorally relevant circuits with temporal and three-dimensional spatial resolution in experimental animals.}, Author = {Guzowski, John F and Timlin, Jerilyn A and Roysam, Badri and McNaughton, Bruce L and Worley, Paul F and Barnes, Carol A}, Date-Added = {2011-03-17 11:34:38 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {21 Activity-development;development;review;Immediate-Early;genes;circuit formation;Circuit structure-function;synapse formation;experience dependent plasticity;Long-Term Potentiation;Long-Term Depression (Physiology);homeostatic plasticity;frontiers review;imaging;microscopy;Technique;optical physiology;optical imaging}, Mesh = {Animals; Brain Mapping; Diagnostic Imaging; Gene Expression; Genes, Immediate-Early; Humans; In Situ Hybridization; Neural Pathways}, Month = {Oct}, Number = {5}, Pages = {599-606}, pmid = {16150584}, Pst = {ppublish}, Title = {Mapping behaviorally relevant neural circuits with immediate-early gene expression}, Volume = {15}, Year = {2005}, url = {papers/Guzowski_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.08.018}} @article{Bramham:2008, Abstract = {In a manner unique among activity-regulated immediate early genes (IEGs), mRNA encoded by Arc (also known as Arg3.1) undergoes rapid transport to dendrites and local synaptic translation. Despite this intrinsic appeal, relatively little is known about the neuronal and behavioral functions of Arc or its molecular mechanisms of action. Here, we attempt to distill recent advances on Arc spanning its transcriptional and translational regulation, the functions of the Arc protein in multiple forms of neuronal plasticity [long-term potentiation (LTP), long-term depression (LTD), and homeostatic plasticity], and its broader role in neural networks of behaving animals. Worley and colleagues have shown that Arc interacts with endophilin and dynamin, creating a postsynaptic trafficking endosome that selectively modifies the expression of AMPA-type glutamate receptors at the excitatory synapses. Both LTD and homeostatic plasticity in the hippocampus are critically dependent on Arc-mediated endocytosis of AMPA receptors. LTD evoked by activation of metabotropic glutamate receptors depends on rapid Arc translation controlled by elongation factor 2. Bramham and colleagues have shown that sustained translation of newly induced Arc mRNA is necessary for cofilin phosphorylation and stable expansion of the F-actin cytoskeleton underlying LTP consolidation in the dentate gyrus of live rats. In addition to regulating F-actin, Arc synthesis maintains the activity of key translation factors during LTP consolidation. This process of Arc-dependent consolidation is activated by the secretory neurotrophin, BDNF. Moore and colleagues have shown that Arc mRNA is a natural target for nonsense-mediated mRNA decay (NMD) by virtue of its two conserved 3'-UTR introns. NMD and other related translation-dependent mRNA decay mechanisms may serve as critical brakes on protein expression that contribute to the fine spatial-temporal control of Arc synthesis. In studies in behaving rats, Guzowski and colleagues have shown that location-specific firing of CA3 and CA1 hippocampal neurons in the presence of theta rhythm provides the necessary stimuli for activation of Arc transcription. The impact of Arc transcription in memory processes may depend on the specific context of coexpressed IEGs, in addition to posttranscriptional regulation of Arc by neuromodulatory inputs from the amygdala and other brain regions. In sum, Arc is emerging as a versatile, finely tuned system capable of coupling changes in neuronal activity patterns to diverse forms of synaptic plasticity, thereby optimizing information storage in active networks.}, Author = {Bramham, Clive R and Worley, Paul F and Moore, Melissa J and Guzowski, John F}, Date-Added = {2011-03-17 11:02:17 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;circuit formation;synapse formation;Synapses;21 Neurophysiology;Electrophysiology;Immediate-Early;gene;Long-Term Potentiation;Long-Term Depression (Physiology);experience dependent plasticity;homeostatic plasticity}, Mesh = {Animals; Brain; Cytoskeletal Proteins; Humans; Nerve Net; Nerve Tissue Proteins; Neuronal Plasticity; RNA Stability; Synapses; Synaptic Transmission; Transcription, Genetic}, Month = {Nov}, Number = {46}, Pages = {11760-7}, Pmc = {PMC2615463}, pmid = {19005037}, Pst = {ppublish}, Title = {The immediate early gene arc/arg3.1: regulation, mechanisms, and function}, Volume = {28}, Year = {2008}, url = {papers/Bramham_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3864-08.2008}} @article{Lichtman:2008, Abstract = {Developmental neurobiology has been greatly invigorated by a recent string of breakthroughs in molecular biology and optical physics that permit direct in vivo observation of neural circuit assembly. The imaging done thus far suggests that as brains are built, a significant amount of unbuilding is also occurring. We offer the view that this tumult is the result of the intersecting behaviors of the many single-celled creatures (i.e., neurons, glia, and progenitors) that inhabit brains. New tools will certainly be needed if we wish to monitor the myriad cooperative and competitive interactions at play in the cellular society that builds brains.}, Author = {Lichtman, Jeff W and Smith, Stephen J}, Date-Added = {2011-03-17 10:32:13 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;development;structural remodeling;Imaging;optical physiology;microscopy;in vivo;Zebrafish;review;circuit formation;Competitive Behavior;Cooperative Behavior;Theoretical;evolutionary dynamics;Evolution;frontiers review}, Mesh = {Animals; Brain; Green Fluorescent Proteins; Humans; Microscopy; Nerve Net; Neural Pathways; Neuroglia; Neurons}, Month = {Nov}, Number = {3}, Pages = {441-8}, Pmc = {PMC2661113}, pmid = {18995818}, Pst = {ppublish}, Title = {Seeing circuits assemble}, Volume = {60}, Year = {2008}, url = {papers/Lichtman_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.10.040}} @article{Gandhi:2008, Abstract = {During postnatal development, altered sensory experience triggers the rapid reorganization of neuronal responses and connections in sensory neocortex. This experience-dependent plasticity is disrupted by reductions of intracortical inhibition. Little is known about how the responses of inhibitory cells themselves change during plasticity. We investigated the time course of inhibitory cell plasticity in mouse primary visual cortex by using functional two-photon microscopy with single-cell resolution and genetic identification of cell type. Initially, local inhibitory and excitatory cells had similar binocular visual response properties, both favoring the contralateral eye. After 2 days of monocular visual deprivation, excitatory cell responses shifted to favor the open eye, whereas inhibitory cells continued to respond more strongly to the deprived eye. By 4 days of deprivation, inhibitory cell responses shifted to match the faster changes in their excitatory counterparts. These findings reveal a dramatic delay in inhibitory cell plasticity. A minimal linear model reveals that the delay in inhibitory cell plasticity potently accelerates Hebbian plasticity in neighboring excitatory neurons. These findings offer a network-level explanation as to how inhibition regulates the experience-dependent plasticity of neocortex.}, Author = {Gandhi, Sunil P and Yanagawa, Yuchio and Stryker, Michael P}, Date-Added = {2011-03-16 23:48:50 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Activity-development;calcium imaging;optical physiology;optical imaging;in vivo;mouse;mice;Transgenic;Visual Cortex;experience dependent plasticity;Sensory Deprivation}, Mesh = {Animals; Dominance, Ocular; Mice; Microscopy; Neuronal Plasticity; Photic Stimulation; Visual Cortex; Visual Pathways}, Month = {Oct}, Number = {43}, Pages = {16797-802}, Pmc = {PMC2575499}, pmid = {18940923}, Pst = {ppublish}, Title = {Delayed plasticity of inhibitory neurons in developing visual cortex}, Volume = {105}, Year = {2008}, url = {papers/Gandhi_ProcNatlAcadSciUSA2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0806159105}} @article{Kaneda:2008, Abstract = {The current dominant concept for the control of saccadic eye movements by the basal ganglia is that release from tonic GABAergic inhibition by the substantia nigra pars reticulata (SNr) triggers burst firings of intermediate gray layer (SGI) neurons in the superior colliculus (SC) to allow saccade initiation. This hypothesis is based on the assumption that SNr cells inhibit excitatory projection neurons in the SGI. Here we show that nigrotectal fibers are connected to local GABAergic neurons in the SGI with a similar frequency to non-GABAergic neurons. This was accomplished by applying neuroanatomical tracing and slice electrophysiological experiments in GAD67-green fluorescent protein (GFP) knock-in mice, in which GABAergic neurons specifically express GFP. We also found that GABA(A), but not GABA(B), receptors subserve nigrotectal transmission. The present results revealed a novel aspect on the role of the basal ganglia in the control of saccades, e.g., the SNr not only regulates burst initiation but also modulates the spatiotemporal properties of premotor neurons via connections to local GABAergic neurons in the SC.}, Author = {Kaneda, Katsuyuki and Isa, Kaoru and Yanagawa, Yuchio and Isa, Tadashi}, Date-Added = {2011-03-16 19:10:37 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology;21 Circuit structure-function;GABA;Interneurons;mouse;mice;Superior Colliculus;optic tectum;Electrophysiology;in vitro;Anatomy;Transgenic;connectivity;function}, Mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione; Action Potentials; Animals; Animals, Newborn; Biotin; Dextrans; Electric Stimulation; Excitatory Amino Acid Antagonists; Glutamate Decarboxylase; Green Fluorescent Proteins; Inhibitory Postsynaptic Potentials; Lysine; Membrane Potentials; Mice; Mice, Transgenic; Nerve Fibers; Neural Inhibition; Neural Pathways; Neurons; Patch-Clamp Techniques; Substantia Nigra; Superior Colliculi; gamma-Aminobutyric Acid}, Month = {Oct}, Number = {43}, Pages = {11071-8}, pmid = {18945914}, Pst = {ppublish}, Title = {Nigral inhibition of GABAergic neurons in mouse superior colliculus}, Volume = {28}, Year = {2008}, url = {papers/Kaneda_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3263-08.2008}} @article{Phongphanphanee:2008, Abstract = {The onset and vector of orienting behaviors, such as saccades, are controlled by commands that descend from a population of neurons in deep layers of the superior colliculus (dSC). In this study, to characterize the role of the collicular local circuitry that generates the spatiotemporal pattern of command activity in the dSC neuronal population, responses evoked by single-pulse electrical stimulation in superficial layers of the superior colliculus (sSC) were analyzed by a 64-channel field potential recording system (planar electrode, 8 x 8 pattern; 150 microm interelectrode spacing) in slices obtained from 16- to 22-d-old mice. A negative field potential with short latency and short duration spatially restricted to the recording sites in sSC was evoked adjacent to the stimulation site. After bath application of 10 mum bicuculline, the same stimulus induced a large negative field response with long duration that spread from sSC to dSC. The dSC potential initially showed a positive response, presumably because of reversal of the negative potential that originated in sSC, and then a long negative response that spread horizontally as far as 1 mm. These responses disappeared after application of an NMDA receptor antagonist, 2-amino-5-phosphonovelarate, indicating that NMDA receptors have an important role in the generation of these responses. Simultaneous whole-cell patch-clamp recordings showed that the long-lasting negative field potentials corresponded to the depolarization accompanying burst spike activity of SC neurons. The present study revealed an extensive excitatory network in the dSC that may contribute to the generation of activity by a large population of neurons that discharge before a saccade.}, Author = {Phongphanphanee, Penphimon and Kaneda, Katsuyuki and Isa, Tadashi}, Date-Added = {2011-03-16 19:08:43 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology;Electrophysiology;extracellular;Electroencephalography;LFP;Superior Colliculus;optic tectum;mouse;mice;adult;multielectrode;network}, Mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Animals, Newborn; Bicuculline; Electric Stimulation; Electrophysiology; Evoked Potentials; Excitatory Amino Acid Antagonists; GABA Antagonists; Membrane Potentials; Mice; Mice, Inbred C57BL; Microelectrodes; Neurons; Patch-Clamp Techniques; Spectrum Analysis; Superior Colliculi; Valine}, Month = {Sep}, Number = {37}, Pages = {9309-18}, pmid = {18784311}, Pst = {ppublish}, Title = {Spatiotemporal profiles of field potentials in mouse superior colliculus analyzed by multichannel recording}, Volume = {28}, Year = {2008}, url = {papers/Phongphanphanee_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1905-08.2008}} @article{Scanziani:2009, Abstract = {Electrophysiology, the 'gold standard' for investigating neuronal signalling, is being challenged by a new generation of optical probes. Together with new forms of microscopy, these probes allow us to measure and control neuronal signals with spatial resolution and genetic specificity that already greatly surpass those of electrophysiology. We predict that the photon will progressively replace the electron for probing neuronal function, particularly for targeted stimulation and silencing of neuronal populations. Although electrophysiological characterization of channels, cells and neural circuits will remain necessary, new combinations of electrophysiology and imaging should lead to transformational discoveries in neuroscience.}, Author = {Scanziani, Massimo and H{\"a}usser, Michael}, Date-Added = {2011-03-16 18:40:05 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology;optical imaging;calcium imaging;calcium sensor;voltage sensor;Technique;review;optogenetics;frontiers review}, Mesh = {Animals; Calcium; Electrophysiology; Light; Neurosciences; Optics and Photonics}, Month = {Oct}, Number = {7266}, Pages = {930-9}, pmid = {19829373}, Pst = {ppublish}, Title = {Electrophysiology in the age of light}, Volume = {461}, Year = {2009}, url = {papers/Scanziani_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08540}} @article{Madisen:2010, Abstract = {The Cre/lox system is widely used in mice to achieve cell-type-specific gene expression. However, a strong and universally responding system to express genes under Cre control is still lacking. We have generated a set of Cre reporter mice with strong, ubiquitous expression of fluorescent proteins of different spectra. The robust native fluorescence of these reporters enables direct visualization of fine dendritic structures and axonal projections of the labeled neurons, which is useful in mapping neuronal circuitry, imaging and tracking specific cell populations in vivo. Using these reporters and a high-throughput in situ hybridization platform, we are systematically profiling Cre-directed gene expression throughout the mouse brain in several Cre-driver lines, including new Cre lines targeting different cell types in the cortex. Our expression data are displayed in a public online database to help researchers assess the utility of various Cre-driver lines for cell-type-specific genetic manipulation.}, Author = {Madisen, Linda and Zwingman, Theresa A and Sunkin, Susan M and Oh, Seung Wook and Zariwala, Hatim A and Gu, Hong and Ng, Lydia L and Palmiter, Richard D and Hawrylycz, Michael J and Jones, Allan R and Lein, Ed S and Zeng, Hongkui}, Date-Added = {2011-03-16 18:11:19 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {genes;Transgenic;Transgenes;Technique;mice;mouse;Structural;Anatomy;Fluorescent Dyes;fluorescent proteins;imaging;21 Circuit structure-function;frontiers review;connectivity;optical imaging;optical physiology;calcium imaging}, Mesh = {Animals; Bacterial Proteins; Brain; Dendrites; Gene Transfer Techniques; Integrases; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Neurons; Promoter Regions, Genetic; Recombination, Genetic; Regulatory Sequences, Nucleic Acid; Tamoxifen; Tissue Distribution; Viral Proteins}, Month = {Jan}, Number = {1}, Pages = {133-40}, Pmc = {PMC2840225}, pmid = {20023653}, Pst = {ppublish}, Title = {A robust and high-throughput Cre reporting and characterization system for the whole mouse brain}, Volume = {13}, Year = {2010}, url = {papers/Madisen_NatNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2467}} @article{Yang:2010, Abstract = {Imaging neurons, glia and vasculature in the living brain has become an important experimental tool for understanding how the brain works. Here we describe in detail a protocol for imaging cortical structures at high optical resolution through a thinned-skull cranial window in live mice using two-photon laser scanning microscopy (TPLSM). Surgery can be performed within 30-45 min and images can be acquired immediately thereafter. The procedure can be repeated multiple times allowing longitudinal imaging of the cortex over intervals ranging from days to years. Imaging through a thinned-skull cranial window avoids exposure of the meninges and the cortex, thus providing a minimally invasive approach for studying structural and functional changes of cells under normal and pathological conditions in the living brain.}, Author = {Yang, Guang and Pan, Feng and Parkhurst, Christopher N and Grutzendler, Jaime and Gan, Wen-Biao}, Date-Added = {2011-03-16 18:09:05 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Protoc}, Journal-Full = {Nature protocols}, Keywords = {Technique;mice;mouse;in vivo;Surgical;multiphoton;microscopy;optical physiology;optical imaging;optics;frontiers review}, Mesh = {Animals; Axons; Cerebral Cortex; Dendrites; Equipment Design; Indicators and Reagents; Luminescent Proteins; Mice; Mice, Transgenic; Microscopy, Confocal; Neurons; Photons; Skull; Synapses}, Number = {2}, Pages = {201-8}, pmid = {20134419}, Pst = {ppublish}, Title = {Thinned-skull cranial window technique for long-term imaging of the cortex in live mice}, Volume = {5}, Year = {2010}, url = {papers/Yang_NatProtoc2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nprot.2009.222}} @article{Horikawa:2010, Abstract = {We report ultrasensitive Ca(2+) indicators, yellow cameleon-Nano (YC-Nano), developed by engineering the Ca(2+)-sensing domain of a genetically encoded Ca(2+) indicator, YC2.60 or YC3.60. Their high Ca(2+) affinities (K(d) = 15-140 nM) and large signal change (1,450\%) enabled detection of subtle Ca(2+) transients associated with intercellular signaling dynamics and neuronal activity, even in 100,000-cell networks. These indicators will be useful for studying information processing in living multicellular networks.}, Author = {Horikawa, Kazuki and Yamada, Yoshiyuki and Matsuda, Tomoki and Kobayashi, Kentarou and Hashimoto, Mitsuhiro and Matsu-ura, Toru and Miyawaki, Atsushi and Michikawa, Takayuki and Mikoshiba, Katsuhiko and Nagai, Takeharu}, Date-Added = {2011-03-16 17:55:05 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology;optical imaging;calcium sensor;calcium imaging;Technique;frontiers review;genes;}, Mesh = {Animals; Calcium; Dictyostelium; Fluorescent Dyes; Indicators and Reagents; Mice; Molecular Sequence Data; Neurons; Signal Transduction; Zebrafish}, Month = {Sep}, Number = {9}, Pages = {729-32}, pmid = {20693999}, Pst = {ppublish}, Title = {Spontaneous network activity visualized by ultrasensitive Ca(2+) indicators, yellow Cameleon-Nano}, Volume = {7}, Year = {2010}, url = {papers/Horikawa_NatMethods2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1488}} @article{Cheng:2011, Abstract = {In vivo two-photon calcium imaging would benefit from the use of multiple excitation beams to increase scanning speed, signal-to-noise ratio and field of view or to image different axial planes simultaneously. Using spatiotemporal multiplexing we circumvented light-scattering ambiguity inherent to deep-tissue multifocal two-photon microscopy. We demonstrate calcium imaging at multiple axial planes in the intact mouse brain to monitor network activity of ensembles of cortical neurons in three spatial dimensions.}, Author = {Cheng, Adrian and Gon{\c c}alves, J Tiago and Golshani, Peyman and Arisaka, Katsushi and Portera-Cailliau, Carlos}, Date-Added = {2011-03-16 17:41:12 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology;optical imaging;Technique;microscopy;multiphoton;optics;calcium imaging;Neocortex;mouse;mice;in vivo;frontiers review}, Mesh = {Animals; Brain; Brain Chemistry; Calcium; Mice; Microscopy, Fluorescence, Multiphoton; Time Factors}, Month = {Feb}, Number = {2}, Pages = {139-42}, pmid = {21217749}, Pst = {ppublish}, Title = {Simultaneous two-photon calcium imaging at different depths with spatiotemporal multiplexing}, Volume = {8}, Year = {2011}, url = {papers/Cheng_NatMethods2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1552}} @article{Diester:2011, Abstract = {Optogenetics is a technique for controlling subpopulations of neurons in the intact brain using light. This technique has the potential to enhance basic systems neuroscience research and to inform the mechanisms and treatment of brain injury and disease. Before launching large-scale primate studies, the method needs to be further characterized and adapted for use in the primate brain. We assessed the safety and efficiency of two viral vector systems (lentivirus and adeno-associated virus), two human promoters (human synapsin (hSyn) and human thymocyte-1 (hThy-1)) and three excitatory and inhibitory mammalian codon-optimized opsins (channelrhodopsin-2, enhanced Natronomonas pharaonis halorhodopsin and the step-function opsin), which we characterized electrophysiologically, histologically and behaviorally in rhesus monkeys (Macaca mulatta). We also introduced a new device for measuring in vivo fluorescence over time, allowing minimally invasive assessment of construct expression in the intact brain. We present a set of optogenetic tools designed for optogenetic experiments in the non-human primate brain.}, Author = {Diester, Ilka and Kaufman, Matthew T and Mogri, Murtaza and Pashaie, Ramin and Goo, Werapong and Yizhar, Ofer and Ramakrishnan, Charu and Deisseroth, Karl and Shenoy, Krishna V}, Date-Added = {2011-03-16 17:38:10 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {optogenetics;optical physiology;viral gene transfer;Virus;Technique;}, Month = {Mar}, Number = {3}, Pages = {387-97}, pmid = {21278729}, Pst = {ppublish}, Title = {An optogenetic toolbox designed for primates}, Volume = {14}, Year = {2011}, url = {papers/Diester_NatNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2749}} @article{Kuczewski:2008, Abstract = {Brain-derived neurotrophic factor (BDNF) is a major regulator of activity-dependent synapse development and plasticity. Because BDNF is a secreted protein, it has been proposed that BDNF is released from target neurons in an activity-dependent manner. However, direct evidence for postsynaptic release of BDNF triggered by ongoing network activity is still lacking. Here we transfected cultures of dissociated hippocampal neurons with green fluorescent protein (GFP)-tagged BDNF and combined whole-cell recording, time-lapse fluorescent imaging, and immunostaining to monitor activity-dependent dendritic release of BDNF. We found that spontaneous backpropagating action potentials, but not synaptic activity alone, led to a Ca2+-dependent dendritic release of BDNF-GFP. Moreover, we provide evidence that endogenous BDNF released from a single neuron can phosphorylate CREB (cAMP response element-binding protein) in neighboring neurons, an important step of immediate early gene activation. Therefore, together, our results support the hypothesis that BDNF might act as a target-derived messenger of activity-dependent synaptic plasticity and development.}, Author = {Kuczewski, Nicola and Porcher, Christophe and Ferrand, Nadine and Fiorentino, Herv{\'e} and Pellegrino, Christophe and Kolarow, Richard and Lessmann, Volkmar and Medina, Igor and Gaiarsa, Jean-Luc}, Date-Added = {2011-03-16 17:36:24 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;21 Circuit structure-function;Spontaneous activity;genes;molecules;BDNF;trophic signal;Competitive Behavior;in vitro;21 Neurophysiology;Electrophysiology;evolutionary dynamics}, Mesh = {Action Potentials; Animals; Animals, Newborn; Brain-Derived Neurotrophic Factor; Calcium Signaling; Cell Differentiation; Cells, Cultured; Cyclic AMP Response Element-Binding Protein; Dendrites; Gene Expression Regulation; Genes, Immediate-Early; Green Fluorescent Proteins; Hippocampus; Immunohistochemistry; Nerve Net; Neuronal Plasticity; Patch-Clamp Techniques; Phosphorylation; Rats; Recombinant Fusion Proteins; Staining and Labeling; Synaptic Transmission; Transcriptional Activation}, Month = {Jul}, Number = {27}, Pages = {7013-23}, pmid = {18596175}, Pst = {ppublish}, Title = {Backpropagating action potentials trigger dendritic release of BDNF during spontaneous network activity}, Volume = {28}, Year = {2008}, url = {papers/Kuczewski_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1673-08.2008}} @article{Dhande:2011, Abstract = {The maturation of retinal ganglion cell (RGC) axon projections in the dorsal lateral geniculate nucleus (dLGN) and the superior colliculus (SC) relies on both molecular and activity-dependent mechanisms. Despite the increasing popularity of the mouse as a mammalian visual system model, little is known in this species about the normal development of individual RGC axon arbors or the role of activity in this process. We used a novel in vivo single RGC labeling technique to quantitatively characterize the elaboration and refinement of RGC axon arbors in the dLGN and SC in wild-type (WT) and β2-nicotinic acetylcholine receptors mutant (β2(-/-)) mice, which have perturbed retinal waves, during the developmental period when eye-specific lamination and retinotopic refinement occurs. Our results suggest that eye-specific segregation and retinotopic refinement in WT mice are not the result of refinement of richly exuberant arbors but rather the elaboration of arbors prepositioned in the proper location combined with the elimination of inappropriately targeted sparse branches. We found that retinocollicular arbors mature ∼1 week earlier than retinogeniculate arbors, although RGC axons reach the dLGN and SC at roughly the same age. We also observed striking differences between contralateral and ipsilateral RGC axon arbors in the SC but not in the LGN. These data suggest a strong influence of target specific cues during arbor maturation. In β2(-/-) mice, we found that retinofugal single axon arbors are well ramified but enlarged, particularly in the SC, indicating that activity-dependent visual map development occurs through the refinement of individual RGC arbors.}, Author = {Dhande, Onkar S and Hua, Ethan W and Guh, Emily and Yeh, Jonathan and Bhatt, Shivani and Zhang, Yueyi and Ruthazer, Edward S and Feller, Marla B and Crair, Michael C}, Date-Added = {2011-03-16 17:33:45 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;structural remodeling;plasticity;development;Spontaneous activity;optic tectum;retina;Superior Colliculus;mouse;mice;Transgenic;Acetylcholine;Nicotinic;retinal wave paper; currOpinRvw}, Month = {Mar}, Number = {9}, Pages = {3384-99}, pmid = {21368050}, Pst = {ppublish}, Title = {Development of Single Retinofugal Axon Arbors in Normal and {beta}2 Knock-Out Mice}, Volume = {31}, Year = {2011}, url = {papers/Dhande_JNeurosci2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4899-10.2011}} @article{Xu:2010, Abstract = {Emerging evidence suggests that immune proteins regulate activity-dependent synapse formation in the central nervous system (CNS). Mice with mutations in class I major histocompatibility complex (MHCI) genes have incomplete eye-specific segregation of retinal ganglion cell (RGC) axon projections to the CNS. This effect has been attributed to causes that are nonretinal in origin. We show that a key component of MHCI receptor, CD3zeta, is expressed in RGCs. CD3zeta-deficient mice have reduced RGC dendritic motility, an increase in RGC dendritic density, and a selective defect of glutamate-receptor-mediated synaptic activity in the retina. Disrupted RGC synaptic activity and dendritic motility is associated with a failure of eye-specific segregation of RGC axon projections to the CNS. These results provide direct evidence of an unrecognized requirement for immune proteins in the developmental regulation of RGC synaptic wiring and indicate a possible retinal origin for the disruption of eye-specific segregation found in immune-deficient mice.}, Author = {Xu, Hong-ping and Chen, Hui and Ding, Qian and Xie, Zheng-Hua and Chen, Ling and Diao, Ling and Wang, Ping and Gan, Lin and Crair, Michael C and Tian, Ning}, Date-Added = {2011-03-16 17:28:51 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;Spontaneous activity;MHC Class I;genes;retina;Superior Colliculus;optic tectum;development;21 Neurophysiology;extracellular;retinal wave paper}, Mesh = {Animals; Antigens, CD3; Cell Movement; Dendrites; Fluorescent Antibody Technique; Glutamic Acid; Mice; Mice, Knockout; Nerve Net; Receptors, Glutamate; Retina; Retinal Ganglion Cells; Reverse Transcriptase Polymerase Chain Reaction; Synapses; Synaptic Transmission; Visual Pathways}, Month = {Feb}, Number = {4}, Pages = {503-15}, Pmc = {PMC3037728}, pmid = {20188655}, Pst = {ppublish}, Title = {The immune protein CD3zeta is required for normal development of neural circuits in the retina}, Volume = {65}, Year = {2010}, url = {papers/Xu_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.01.035}} @article{Wang:2003b, Abstract = {An understanding of the logic of odor perception requires a functional analysis of odor-evoked patterns of activity in neural assemblies in the brain. We have developed a sensitive imaging system in the Drosophila brain that couples two-photon microscopy with the specific expression of the calcium-sensitive fluorescent protein, G-CaMP. At natural odor concentration, each odor elicits a distinct and sparse spatial pattern of activity in the antennal lobe that is conserved in different flies. Patterns of glomerular activity are similar upon imaging of sensory and projection neurons, suggesting the faithful transmission of sensory input to higher brain centers. Finally, we demonstrate that the response pattern of a given glomerulus is a function of the specificity of a single odorant receptor. The development of this imaging system affords an opportunity to monitor activity in defined neurons throughout the fly brain with high sensitivity and excellent spatial resolution.}, Author = {Wang, Jing W and Wong, Allan M and Flores, Jorge and Vosshall, Leslie B and Axel, Richard}, Date-Added = {2011-03-16 17:15:17 -0400}, Date-Modified = {2011-03-16 17:16:34 -0400}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {21 Circuit structure-function;21 Neurophysiology;Multiphoton;microscopy;optical physiology;optical imaging;Drosophila;Olfactory Bulb;calcium imaging;calcium sensor;frontiers review}, Mesh = {Animals; Axons; Brain; Calcium; Calcium Signaling; Dendrites; Diagnostic Imaging; Drosophila; Ganglia, Invertebrate; Odors; Olfactory Pathways; Olfactory Receptor Neurons; Photons; Smell}, Month = {Jan}, Number = {2}, Pages = {271-82}, pmid = {12553914}, Pst = {ppublish}, Title = {Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain}, Volume = {112}, Year = {2003}, url = {papers/Wang_Cell2003.pdf}} @article{Cardin:2009, Abstract = {Cortical gamma oscillations (20-80 Hz) predict increases in focused attention, and failure in gamma regulation is a hallmark of neurological and psychiatric disease. Current theory predicts that gamma oscillations are generated by synchronous activity of fast-spiking inhibitory interneurons, with the resulting rhythmic inhibition producing neural ensemble synchrony by generating a narrow window for effective excitation. We causally tested these hypotheses in barrel cortex in vivo by targeting optogenetic manipulation selectively to fast-spiking interneurons. Here we show that light-driven activation of fast-spiking interneurons at varied frequencies (8-200 Hz) selectively amplifies gamma oscillations. In contrast, pyramidal neuron activation amplifies only lower frequency oscillations, a cell-type-specific double dissociation. We found that the timing of a sensory input relative to a gamma cycle determined the amplitude and precision of evoked responses. Our data directly support the fast-spiking-gamma hypothesis and provide the first causal evidence that distinct network activity states can be induced in vivo by cell-type-specific activation.}, Author = {Cardin, Jessica A and Carl{\'e}n, Marie and Meletis, Konstantinos and Knoblich, Ulf and Zhang, Feng and Deisseroth, Karl and Tsai, Li-Huei and Moore, Christopher I}, Date-Added = {2011-03-16 17:05:15 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Neurophysiology;Electrophysiology;extracellular;optogenetics;optical physiology;Technique;21 Circuit structure-function;connectivity;neocortex;visual system;visual cortex;frontiers review;Mouse;Transgenic;Mice;function;}, Mesh = {Animals; Chlamydomonas reinhardtii; Electrophysiology; Gene Expression Regulation; Gene Knock-In Techniques; Interneurons; Mice; Photic Stimulation; Pyramidal Cells; Rhodopsin; Somatosensory Cortex}, Month = {Jun}, Number = {7247}, Pages = {663-7}, pmid = {19396156}, Pst = {ppublish}, Title = {Driving fast-spiking cells induces gamma rhythm and controls sensory responses}, Volume = {459}, Year = {2009}, url = {papers/Cardin_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08002}} @article{Cardin:2008, Abstract = {Gain modulation is a widespread neuronal phenomenon that modifies response amplitude without changing selectivity. Computational and in vitro studies have proposed cellular mechanisms of gain modulation based on the postsynaptic effects of background synaptic activation, but these mechanisms have not been studied in vivo. Here, we used intracellular recordings from cat primary visual cortex to measure neuronal gain while changing background synaptic activity with visual stimulation. We found that increases in the membrane fluctuations associated with increases in synaptic input do not obligatorily result in gain modulation in vivo. However, visual stimuli that evoked sustained changes in resting membrane potential, input resistance, and membrane fluctuations robustly modulated neuronal gain. The magnitude of gain modulation depended critically on the spatiotemporal properties of the visual stimulus. Gain modulation in vivo may thus be determined on a moment-to-moment basis by sensory context and the consequent dynamics of synaptic activation.}, Author = {Cardin, Jessica A and Palmer, Larry A and Contreras, Diego}, Date-Added = {2011-03-16 17:00:31 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Neurophysiology;Electrophysiology;extracellular;21 Circuit structure-function;connectivity;neocortex;visual system;visual cortex;cat}, Mesh = {Action Potentials; Animals; Cats; Computer Simulation; Contrast Sensitivity; Dose-Response Relationship, Radiation; Electric Stimulation; Models, Neurological; Neurons; Patch-Clamp Techniques; Photic Stimulation; Synapses; Synaptic Transmission; Visual Cortex}, Month = {Jul}, Number = {1}, Pages = {150-60}, Pmc = {PMC2504695}, pmid = {18614036}, Pst = {ppublish}, Title = {Cellular mechanisms underlying stimulus-dependent gain modulation in primary visual cortex neurons in vivo}, Volume = {59}, Year = {2008}, url = {papers/Cardin_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.05.002}} @article{Cardin:2007, Abstract = {Although several lines of evidence suggest that stimulus selectivity in somatosensory and visual cortices is critically dependent on unselective inhibition, particularly in the thalamorecipient layer 4, no comprehensive comparison of the responses of excitatory and inhibitory cells has been conducted. Here, we recorded intracellularly from a large population of regular spiking (RS; presumed excitatory) and fast spiking (FS; presumed inhibitory) cells in layers 2-6 of primary visual cortex. In layer 4, where selectivity for orientation and spatial frequency first emerges, we found no untuned FS cells. Instead, the tuning of the spike output of layer 4 FS cells was significantly but moderately broader than that of RS cells. However, the tuning of the underlying synaptic responses was not different, indicating that the difference in spike-output selectivity resulted from differences in the transformation of synaptic input into firing rate. Layer 4 FS cells exhibited significantly lower input resistance and faster time constants than layer 4 RS cells, leading to larger and faster membrane potential (V(m)) fluctuations. FS cell V(m) fluctuations were more broadly tuned than those of RS cells and matched spike-output tuning, suggesting that the broader spike tuning of these cells was driven by visually evoked synaptic noise. These differences were not observed outside of layer 4. Thus, cell type-specific differences in stimulus feature selectivity at the first level of cortical sensory processing may arise as a result of distinct biophysical properties that determine the dynamics of synaptic integration.}, Author = {Cardin, Jessica A and Palmer, Larry A and Contreras, Diego}, Date-Added = {2011-03-16 16:57:35 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology;Electrophysiology;extracellular;21 Circuit structure-function;connectivity;neocortex;visual system;visual cortex;cat}, Mesh = {Animals; Cats; Computer Simulation; Excitatory Postsynaptic Potentials; Inhibitory Postsynaptic Potentials; Interneurons; Models, Neurological; Neural Conduction; Neural Inhibition; Neurons; Photic Stimulation; Visual Cortex}, Month = {Sep}, Number = {39}, Pages = {10333-44}, Pmc = {PMC3025280}, pmid = {17898205}, Pst = {ppublish}, Title = {Stimulus feature selectivity in excitatory and inhibitory neurons in primary visual cortex}, Volume = {27}, Year = {2007}, url = {papers/Cardin_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1692-07.2007}} @article{Douglass:2008, Abstract = {Somatosensory neurons in teleosts and amphibians are sensitive to thermal, mechanical, or nociceptive stimuli [1, 2]. The two main types of such cells in zebrafish--Rohon-Beard and trigeminal neurons--have served as models for neural development [3-6], but little is known about how they encode tactile stimuli. The hindbrain networks that transduce somatosensory stimuli into a motor output encode information by using very few spikes in a small number of cells [7], but it is unclear whether activity in the primary receptor neurons is similarly efficient. To address this question, we manipulated the activity of zebrafish neurons with the light-activated cation channel, Channelrhodopsin-2 (ChR2) [8, 9]. We found that photoactivation of ChR2 in genetically defined populations of somatosensory neurons triggered escape behaviors in 24-hr-old zebrafish. Electrophysiological recordings from ChR2-positive trigeminal neurons in intact fish revealed that these cells have extremely low rates of spontaneous activity and can be induced to fire by brief pulses of blue light. Using this technique, we find that even a single action potential in a single sensory neuron was at times sufficient to evoke an escape behavior. These results establish ChR2 as a powerful tool for the manipulation of neural activity in zebrafish and reveal a degree of efficiency in coding that has not been found in primary sensory neurons.}, Author = {Douglass, Adam D and Kraves, Sebastian and Deisseroth, Karl and Schier, Alexander F and Engert, Florian}, Date-Added = {2011-03-16 16:45:00 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {21 Neurophysiology;optical physiology;optogenetics;function;behavior;Electrophysiology;Zebrafish;Technique;frontiers review}, Mesh = {Animals; Electrophysiology; Embryo, Nonmammalian; Escape Reaction; Evoked Potentials, Somatosensory; Ion Channels; Light; Neurons, Afferent; Photic Stimulation; Trigeminal Nerve; Zebrafish; Zebrafish Proteins}, Month = {Aug}, Number = {15}, Pages = {1133-7}, Pmc = {PMC2891506}, pmid = {18682213}, Pst = {ppublish}, Title = {Escape behavior elicited by single, channelrhodopsin-2-evoked spikes in zebrafish somatosensory neurons}, Volume = {18}, Year = {2008}, url = {papers/Douglass_CurrBiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2008.06.077}} @article{Adamantidis:2007, Abstract = {The neural underpinnings of sleep involve interactions between sleep-promoting areas such as the anterior hypothalamus, and arousal systems located in the posterior hypothalamus, the basal forebrain and the brainstem. Hypocretin (Hcrt, also known as orexin)-producing neurons in the lateral hypothalamus are important for arousal stability, and loss of Hcrt function has been linked to narcolepsy. However, it is unknown whether electrical activity arising from Hcrt neurons is sufficient to drive awakening from sleep states or is simply correlated with it. Here we directly probed the impact of Hcrt neuron activity on sleep state transitions with in vivo neural photostimulation, genetically targeting channelrhodopsin-2 to Hcrt cells and using an optical fibre to deliver light deep in the brain, directly into the lateral hypothalamus, of freely moving mice. We found that direct, selective, optogenetic photostimulation of Hcrt neurons increased the probability of transition to wakefulness from either slow wave sleep or rapid eye movement sleep. Notably, photostimulation using 5-30 Hz light pulse trains reduced latency to wakefulness, whereas 1 Hz trains did not. This study establishes a causal relationship between frequency-dependent activity of a genetically defined neural cell type and a specific mammalian behaviour central to clinical conditions and neurobehavioural physiology.}, Author = {Adamantidis, Antoine R and Zhang, Feng and Aravanis, Alexander M and Deisseroth, Karl and de Lecea, Luis}, Date-Added = {2011-03-16 16:39:09 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Neurophysiology;function;Behavior;optogenetics;optical physiology;Technique;frontiers review;Sleep;activity manipulation}, Mesh = {Animals; Circadian Rhythm; Hypothalamus; Intracellular Signaling Peptides and Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neuropeptides; Patch-Clamp Techniques; Receptors, G-Protein-Coupled; Receptors, Neuropeptide; Rhodopsin; Sleep; Sleep, REM; Wakefulness}, Month = {Nov}, Number = {7168}, Pages = {420-4}, pmid = {17943086}, Pst = {ppublish}, Title = {Neural substrates of awakening probed with optogenetic control of hypocretin neurons}, Volume = {450}, Year = {2007}, url = {papers/Adamantidis_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06310}} @article{Huber:2008, Abstract = {Electrical microstimulation can establish causal links between the activity of groups of neurons and perceptual and cognitive functions. However, the number and identities of neurons microstimulated, as well as the number of action potentials evoked, are difficult to ascertain. To address these issues we introduced the light-gated algal channel channelrhodopsin-2 (ChR2) specifically into a small fraction of layer 2/3 neurons of the mouse primary somatosensory cortex. ChR2 photostimulation in vivo reliably generated stimulus-locked action potentials at frequencies up to 50 Hz. Here we show that naive mice readily learned to detect brief trains of action potentials (five light pulses, 1 ms, 20 Hz). After training, mice could detect a photostimulus firing a single action potential in approximately 300 neurons. Even fewer neurons (approximately 60) were required for longer stimuli (five action potentials, 250 ms). Our results show that perceptual decisions and learning can be driven by extremely brief epochs of cortical activity in a sparse subset of supragranular cortical pyramidal neurons.}, Author = {Huber, Daniel and Petreanu, Leopoldo and Ghitani, Nima and Ranade, Sachin and Hrom{\'a}dka, Tom{\'a}s and Mainen, Zach and Svoboda, Karel}, Date-Added = {2011-03-16 16:34:15 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology;optogenetics;activity manipulation;mice;function;Somatosensory Cortex;neocortex;optics;Technique;21 Neurophysiology;frontiers review}, Mesh = {Action Potentials; Algal Proteins; Animals; Behavior, Animal; Cerebral Cortex; Electric Stimulation; Learning; Mice; Movement; Optics and Photonics; Photic Stimulation; Pyramidal Cells; Rhodopsins, Microbial}, Month = {Jan}, Number = {7174}, Pages = {61-4}, pmid = {18094685}, Pst = {ppublish}, Title = {Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice}, Volume = {451}, Year = {2008}, url = {papers/Huber_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06445}} @article{Grinvald:2004, Abstract = {During the last few decades, neuroscientists have benefited from the emergence of many powerful functional imaging techniques that cover broad spatial and temporal scales. We can now image single molecules controlling cell differentiation, growth and death; single cells and their neurites processing electrical inputs and sending outputs; neuronal circuits performing neural computations in vitro; and the intact brain. At present, imaging based on voltage-sensitive dyes (VSDI) offers the highest spatial and temporal resolution for imaging neocortical functions in the living brain, and has paved the way for a new era in the functional imaging of cortical dynamics. It has facilitated the exploration of fundamental mechanisms that underlie neocortical development, function and plasticity at the fundamental level of the cortical column.}, Author = {Grinvald, Amiram and Hildesheim, Rina}, Date-Added = {2011-03-16 16:21:45 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {21 Neurophysiology;optical physiology;optical imaging;Electrophysiology;voltage sensor;calcium sensor;review;technique;21 Cortical oscillations;frontiers review}, Mesh = {Animals; Brain Mapping; Cerebral Cortex; Coloring Agents; Electrophysiology; Neurology}, Month = {Nov}, Number = {11}, Pages = {874-85}, pmid = {15496865}, Pst = {ppublish}, Title = {VSDI: a new era in functional imaging of cortical dynamics}, Volume = {5}, Year = {2004}, url = {papers/Grinvald_NatRevNeurosci2004.pdf}, eprint = {http://dx.doi.org/10.1038/nrn1536}} @article{Homma:2009, Abstract = {This chapter presents three examples of imaging brain activity with voltage- or calcium-sensitive dyes. Because experimental measurements are limited by low sensitivity, the chapter then discusses the methodological aspects that are critical for optimal signal-to-noise ratio. Two of the examples use wide-field (1-photon) imaging and the third uses two-photon scanning microscopy. These methods have relatively high temporal resolution ranging from 10 to 10,000 Hz. The three examples are the following: (1) Internally injected voltage-sensitive dye can be used to monitor membrane potential in the dendrites of invertebrate and vertebrate neurons in in vitro preparations. These experiments are directed at understanding how individual neurons convert the complex input synaptic activity into the output spike train. (2) Recently developed methods for staining many individual cells in the mammalian brain with calcium-sensitive dyes together with two-photon microscopy made it possible to follow the spike activity of many neurons simultaneously while in vivo preparations are responding to stimulation. (3) Calcium-sensitive dyes that are internalized into olfactory receptor neurons in the nose will, after several days, be transported to the nerve terminals of these cells in the olfactory bulb glomeruli. There, the population signals can be used as a measure of the input from the nose to the bulb. Three kinds of noise in measuring light intensity are discussed: (1) Shot noise from the random emission of photons from the preparation. (2) Extraneous (technical) noise from external sources. (3) Noise that occurs in the absence of light, the dark noise. In addition, we briefly discuss the light sources, the optics, and the detectors and cameras. The commonly used organic voltage and ion sensitive dyes stain all of the cell types in the preparation indiscriminately. A major effort is underway to find methods for staining individual cell types in the brain selectively. Most of these efforts center around fluorescent protein activity sensors because transgenic methods can be used to express them in individual cell types.}, Author = {Homma, Ryota and Baker, Bradley J and Jin, Lei and Garaschuk, Olga and Konnerth, Arthur and Cohen, Lawrence B and Bleau, Chun X and Canepari, Marco and Djurisic, Maja and Zecevic, Dejan}, Date-Added = {2011-03-16 16:18:26 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Methods Mol Biol}, Journal-Full = {Methods in molecular biology (Clifton, N.J.)}, Keywords = {optical physiology;optical imaging;voltage sensor;Technique;review;microscopy;calcium sensor;calcium imaging;frontiers review}, Mesh = {Animals; Brain; Calcium; Coloring Agents; Evoked Potentials; Humans; Photons}, Pages = {43-79}, pmid = {18839087}, Pst = {ppublish}, Title = {Wide-field and two-photon imaging of brain activity with voltage- and calcium-sensitive dyes}, Volume = {489}, Year = {2009}, url = {papers/Homma_MethodsMolBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/978-1-59745-543-5_3}} @article{Petreanu:2009, Abstract = {Understanding cortical circuits will require mapping the connections between specific populations of neurons, as well as determining the dendritic locations where the synapses occur. The dendrites of individual cortical neurons overlap with numerous types of local and long-range excitatory axons, but axodendritic overlap is not always a good predictor of actual connection strength. Here we developed an efficient channelrhodopsin-2 (ChR2)-assisted method to map the spatial distribution of synaptic inputs, defined by presynaptic ChR2 expression, within the dendritic arborizations of recorded neurons. We expressed ChR2 in two thalamic nuclei, the whisker motor cortex and local excitatory neurons and mapped their synapses with pyramidal neurons in layers 3, 5A and 5B (L3, L5A and L5B) in the mouse barrel cortex. Within the dendritic arborizations of L3 cells, individual inputs impinged onto distinct single domains. These domains were arrayed in an orderly, monotonic pattern along the apical axis: axons from more central origins targeted progressively higher regions of the apical dendrites. In L5 arborizations, different inputs targeted separate basal and apical domains. Input to L3 and L5 dendrites in L1 was related to whisker movement and position, suggesting that these signals have a role in controlling the gain of their target neurons. Our experiments reveal high specificity in the subcellular organization of excitatory circuits.}, Author = {Petreanu, Leopoldo and Mao, Tianyi and Sternson, Scott M and Svoboda, Karel}, Date-Added = {2011-03-16 16:15:59 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology;optogenetics;Electrophysiology;21 Circuit structure-function;21 Neurophysiology;connectivity;Technique;frontiers review}, Mesh = {Animals; Axons; Dendrites; Mice; Neocortex; Neural Pathways; Pyramidal Cells; Rhodopsin; Thalamic Nuclei}, Month = {Feb}, Number = {7233}, Pages = {1142-5}, Pmc = {PMC2745650}, pmid = {19151697}, Pst = {ppublish}, Title = {The subcellular organization of neocortical excitatory connections}, Volume = {457}, Year = {2009}, url = {papers/Petreanu_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07709}} @article{Petreanu:2007, Abstract = {The functions of cortical areas depend on their inputs and outputs, but the detailed circuits made by long-range projections are unknown. We show that the light-gated channel channelrhodopsin-2 (ChR2) is delivered to axons in pyramidal neurons in vivo. In brain slices from ChR2-expressing mice, photostimulation of ChR2-positive axons can be transduced reliably into single action potentials. Combining photostimulation with whole-cell recordings of synaptic currents makes it possible to map circuits between presynaptic neurons, defined by ChR2 expression, and postsynaptic neurons, defined by targeted patching. We applied this technique, ChR2-assisted circuit mapping (CRACM), to map long-range callosal projections from layer (L) 2/3 of the somatosensory cortex. L2/3 axons connect with neurons in L5, L2/3 and L6, but not L4, in both ipsilateral and contralateral cortex. In both hemispheres the L2/3-to-L5 projection is stronger than the L2/3-to-L2/3 projection. Our results suggest that laminar specificity may be identical for local and long-range cortical projections.}, Author = {Petreanu, Leopoldo and Huber, Daniel and Sobczyk, Aleksander and Svoboda, Karel}, Date-Added = {2011-03-16 16:11:49 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {optical physiology;optogenetics;Electrophysiology;21 Neurophysiology;21 Circuit structure-function;connectivity;in vitro;Neocortex;Technique;frontiers review}, Mesh = {Animals; Animals, Newborn; Axons; Brain Mapping; Corpus Callosum; Embryo, Mammalian; Female; Functional Laterality; Membrane Potentials; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Net; Neural Pathways; Patch-Clamp Techniques; Photic Stimulation; Pregnancy; Retinaldehyde; Rhodopsin; Somatosensory Cortex}, Month = {May}, Number = {5}, Pages = {663-8}, pmid = {17435752}, Pst = {ppublish}, Title = {Channelrhodopsin-2-assisted circuit mapping of long-range callosal projections}, Volume = {10}, Year = {2007}, url = {papers/Petreanu_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1891}} @article{Haider:2009, Abstract = {The highly interconnected local and large-scale networks of the neocortical sheet rapidly and dynamically modulate their functional connectivity according to behavioral demands. This basic operating principle of the neocortex is mediated by the continuously changing flow of excitatory and inhibitory synaptic barrages that not only control participation of neurons in networks but also define the networks themselves. The rapid control of neuronal responsiveness via synaptic bombardment is a fundamental property of cortical dynamics that may provide the basis of diverse behaviors, including sensory perception, motor integration, working memory, and attention.}, Author = {Haider, Bilal and McCormick, David A}, Date-Added = {2011-03-16 16:09:58 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Cortical oscillations;21 Neurophysiology;review;neocortex;sleep;Technique;Electrophysiology}, Mesh = {Animals; Humans; Membrane Potentials; Models, Neurological; Neocortex; Nerve Net; Neurons; Nonlinear Dynamics; Synaptic Potentials}, Month = {Apr}, Number = {2}, Pages = {171-89}, pmid = {19409263}, Pst = {ppublish}, Title = {Rapid neocortical dynamics: cellular and network mechanisms}, Volume = {62}, Year = {2009}, url = {papers/Haider_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.04.008}} @article{Rospars:1994, Abstract = {The spontaneous activity of first-order neurons (neuroreceptors of the mucosa) and second-order neurons (mitral cells of the bulb) was recorded extracellularly in the frog olfactory system. To assess the influence of peripheral inputs upon mitral cells, the bulb was either normally connected or partially deafferented. Our first set of findings concern the firing behavior. We found that most neurons generated interspike intervals (ISIs) that were stationary in mean and variance, and were not serially correlated at first and second order. Individual spikes in mitral cells and bursts of spikes in neuroreceptors were found to be generated by a Poisson process. Stochastic modeling suggests that the Poissonian behavior depends on the mean value of the membrane potential at the axon hillock. In these models, the mean potential in mitral cells would be far below the firing threshold and in neuroreceptors it would fluctuate at random between two states, one close to resting potential (between bursts) and the other close to the firing threshold with occasional crossings (within bursts). Secondly, partially deafferented mitral cells had significantly higher activity and lower variance than mitral cells receiving normal afferent input. This effect gives evidence that peripheral inputs influence mitral cells at rest not only through direct excitation but also through indirect inhibition exerted by local neurons. Thus, the unstimulated state of the olfactory bulb would not be qualitatively different from its stimulated state in the sense that both states involve the same types of synaptic interactions. Consequently, understanding the synaptic relationships that take place in the bulb network can benefit from studies of its spontaneous activity.}, Author = {Rospars, J P and L{\'a}nsk{\'y}, P and Vaillant, J and Duchamp-Viret, P and Duchamp, A}, Date-Added = {2011-03-16 11:44:31 -0400}, Date-Modified = {2011-03-16 11:47:05 -0400}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {Spontaneous activity;frog;Olfactory Bulb;21 Neurophysiology;Action Potentials;extracellular}, Mesh = {Action Potentials; Animals; Chemoreceptor Cells; Electrophysiology; Models, Neurological; Neurons, Afferent; Olfactory Bulb; Olfactory Mucosa; Olfactory Pathways; Poisson Distribution; Rana ridibunda; Regression Analysis; Smell}, Month = {Oct}, Number = {1-2}, Pages = {31-44}, pmid = {7859089}, Pst = {ppublish}, Title = {Spontaneous activity of first- and second-order neurons in the frog olfactory system}, Volume = {662}, Year = {1994}, url = {papers/Rospars_BrainRes1994.pdf}} @article{Chapman:2000, Abstract = {In the adult mammal, retinal ganglion cell axon arbors are restricted to eye-specific layers in the lateral geniculate nucleus. Blocking neuronal activity early in development prevents this segregation from occurring. To test whether activity is also required to maintain eye-specific segregation, ganglion cell activity was blocked after segregation was established. This caused desegregation, so that both eyes' axons became concentrated in lamina A, normally occupied only by contralateral afferents. These results show that an activity-dependent process is necessary for maintaining eye-specific segregation and suggest that activity-independent cues may favor lamina A as the target for arborization of afferents from both eyes.}, Author = {Chapman, B}, Date-Added = {2011-03-16 11:37:17 -0400}, Date-Modified = {2013-08-27 20:46:38 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Activity-development;Anatomy;Spontaneous activity;retinal wave paper;visual system;LGN;retina;activity manipulation;Ferrets; currOpinRvw}, Mesh = {Aminobutyric Acids; Animals; Axons; Excitatory Amino Acid Agonists; Ferrets; Geniculate Bodies; Retina; Retinal Ganglion Cells; Visual Pathways}, Month = {Mar}, Number = {5462}, Pages = {2479-82}, Pmc = {PMC2637940}, pmid = {10741966}, Pst = {ppublish}, Title = {Necessity for afferent activity to maintain eye-specific segregation in ferret lateral geniculate nucleus}, Volume = {287}, Year = {2000}, url = {papers/Chapman_Science2000.pdf}} @article{Grubb:2003, Abstract = {Spontaneous activity patterns in the developing retina appear important for the functional organization of the visual system. We show here that an absence of early retinal waves in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor (nAChR) is associated with both gain and loss of functional organization in the dorsal lateral geniculate nucleus (dLGN). Anatomical studies show normal gross retinotopy in the beta2(-/-) dLGN but suggest reduced topographic precision in the retinogeniculate projection. Physiological recordings reveal normal topography in the dorsoventral visual axis but a lack of fine-scale mapping in the nasotemporal visual plane. In contrast, unlike wild-type mice, on- and off-center cells in the beta2(-/-) dLGN are spatially segregated. The presence of the beta2 subunit of the nAChR in the CNS is therefore important for normal functional organization in the retinogeniculate projection.}, Author = {Grubb, Matthew S and Rossi, Francesco M and Changeux, Jean Pierre and Thompson, Ian D}, Date-Added = {2011-03-16 11:27:50 -0400}, Date-Modified = {2013-05-29 15:10:59 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;Spontaneous activity;Competitive Behavior;visual system;LGN;retina;Acetylcholine;mice;Transgenic;Nicotinic;21 Neurophysiology;retinal wave paper;in vivo;retinotopy;function;extracellular;activity manipulation; currOpinRvw}, Mesh = {Action Potentials; Animals; Geniculate Bodies; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Pathways; Protein Subunits; Receptors, Nicotinic; Retina}, Month = {Dec}, Number = {6}, Pages = {1161-72}, pmid = {14687550}, Pst = {ppublish}, Title = {Abnormal functional organization in the dorsal lateral geniculate nucleus of mice lacking the beta 2 subunit of the nicotinic acetylcholine receptor}, Volume = {40}, Year = {2003}, url = {papers/Grubb_Neuron2003.pdf}} @article{Hanson:2003, Abstract = {In the developing nervous system, patterned spontaneous activity affects a variety of developmental processes. Thus, it is important to identify the earliest time that such activity occurs and to characterize the underlying circuitry. In isolated mouse spinal cord-limb preparations, highly rhythmic spontaneous activity occurred as early as embryonic day 11 (E11)-E12, when many lumbosacral motoneurons were still migrating and extending their peripheral projections. This activity required both electrical and chemical transmission, and acetylcholine, rather than glutamate, provided the main excitatory drive. Our data are consistent with motoneurons themselves playing a critical role in generating such activity by making excitatory connections on each other and on GABAergic interneurons via dihydro-beta-erythroidine hydrobromide (DHbetaE)-insensitive nicotinic receptors. This resulted in the generation of local bursts. Consistent with these observations, E12-E12.5 mouse motoneurons retrogradely labeled by HRP were observed to have extensive axon collaterals that projected locally within the lateral motor column and to interneuron-containing regions dorsal and medial of the lateral motor column. Cholinergic axons, presumably from motoneurons, were also observed in the ventral and lateral funiculi. However, for local bursts to propagate throughout the cord, a second DHbetaE-sensitive cholinergic pathway that also involved glycinergic interneurons was required. This circuit characterization should facilitate the use of genetic mutations that alter specific subpopulations of interneurons or cholinergic transmission to determine how modifying different aspects of this early activity affects subsequent development of the spinal motor circuit.}, Author = {Hanson, M Gartz and Landmesser, Lynn T}, Date-Added = {2011-03-13 22:39:08 -0400}, Date-Modified = {2011-03-13 22:41:02 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity;mouse;Spinal Cord;Synapses;Synaptic Transmission;21 Activity-development;21 Neurophysiology;in vitro;Acetylcholine;GABA;Embryo and Fetal Development;frontiers review}, Mesh = {Acetylcholine; Action Potentials; Animals; Axons; Electric Stimulation; Excitatory Amino Acid Antagonists; GABA Antagonists; Gap Junctions; Glutamic Acid; Glycine; Hindlimb; Interneurons; Mice; Mice, Inbred C57BL; Motor Neurons; Movement; Neural Pathways; Periodicity; Receptors, Nicotinic; Spinal Cord; Synaptic Transmission; gamma-Aminobutyric Acid}, Month = {Jan}, Number = {2}, Pages = {587-600}, pmid = {12533619}, Pst = {ppublish}, Title = {Characterization of the circuits that generate spontaneous episodes of activity in the early embryonic mouse spinal cord}, Volume = {23}, Year = {2003}, url = {papers/Hanson_JNeurosci2003.pdf}} @article{Lippe:1994, Abstract = {Microelectrode recordings of spontaneous multiple unit activity were made from nucleus magnocellularis (NM) and nucleus laminaris (NL), second- and third-order nuclei in the chick auditory system, between 14 and 19 d of incubation (E14-E19). Spontaneous firing in E14-E18 embryos occurred in synchronous bursts at periodic intervals. A rhythmic pattern of spontaneous firing was also observed in the auditory nerve but not in nonauditory regions of the brain-stem. The mean interburst interval in NM and NL decreased from 4.9 sec at E14-E15 to 2.1 sec at E18. By E19, 2 d prior to hatching, synchronous bursting was replaced by an unpatterned, steady level of firing comparable to the background discharge that is present in NM and NL of hatchling birds. Bursting was not correlated with heart beat or respiration and was not affected by removal of the middle-ear ossicle. Rhythmic bursting could be reset, blocked, or induced by sound stimulation. Cochlea removal or pharmacological blockade of auditory nerve activity with TTX eliminated bursting. These results indicate that the synchrony and rhythmicity of impulse firing reflect normal physiological activity, most likely of cochlear origin. The present findings show that spontaneous activity in the embryonic avian auditory system, like that in the immature mammalian visual pathway (Maffei and Galli-Resta, 1990; Meister et al., 1991), occurs in a synchronously rhythmic pattern. This similarity raises the possibility that such activity may be a general feature of early sensory system development. Patterned spontaneous firing in the chick takes place during a period of embryogenesis when auditory thresholds are high and when it is unlikely that physiological function in ovo is influenced significantly by normally occurring levels of airborne sound. Brainstem auditory neurons undergo substantial changes in structure and innervation during this same period. It is speculated that the temporal pattern of spontaneous discharge may provide cues that contribute to these developmental events.}, Author = {Lippe, W R}, Date-Added = {2011-03-13 22:20:23 -0400}, Date-Modified = {2011-03-13 22:21:33 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity;21 Activity-development;21 Neurophysiology;Auditory Pathways;Cochlear Nerve;Chick Embryo}, Mesh = {Acoustic Stimulation; Animals; Auditory Pathways; Chick Embryo; Cochlea; Nerve Block; Neurons; Periodicity; Tetrodotoxin; Vestibulocochlear Nerve}, Month = {Mar}, Number = {3 Pt 2}, Pages = {1486-95}, pmid = {8126550}, Pst = {ppublish}, Title = {Rhythmic spontaneous activity in the developing avian auditory system}, Volume = {14}, Year = {1994}, url = {papers/Lippe_JNeurosci1994.pdf}} @article{Jones:2007a, Abstract = {Spontaneous neural activity has been recorded in the auditory nerve of cats as early as 2 days postnatal (P2), yet individual auditory neurons do not respond to ambient sound levels <90-100 dB SPL until about P10. Significant refinement of the central projections from the spiral ganglion to the cochlear nucleus occurs during this neonatal period. This refinement may be dependent on peripheral spontaneous discharge activity. We recorded from single spiral ganglion cells in kittens aged P3-P9. The spiral ganglion was accessed through the round window through the spiral lamina. A total of 112 ganglion cells were isolated for study in nine animals. Spike rates in neonates were very low, ranging from 0.06 to 56 spikes/s, with a mean of 3.09 +/- 8.24 spikes/s. Ganglion cells in neonatal kittens exhibited remarkable repetitive spontaneous bursting discharge patterns. The unusual patterns were evident in the large mean interval CV (CV(i) = 2.9 +/- 1.6) and burst index of 5.2 +/- 3.5 across ganglion cells. Spontaneous bursting patterns in these neonatal mammals were similar to those reported for cochlear ganglion cells of the embryonic chicken, suggesting this may be a general phenomenon that is common across animal classes. Rhythmic spontaneous discharge of retinal ganglion cells has been shown to be important in the development of central retinotopic projections and normal binocular vision. Bursting rhythms in cochlear ganglion cells may play a similar role in the auditory system during prehearing periods.}, Author = {Jones, Timothy A and Leake, Patricia A and Snyder, Russell L and Stakhovskaya, Olga and Bonham, Ben}, Date-Added = {2011-03-13 22:17:24 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Spontaneous activity;21 Activity-development;21 Neurophysiology;extracellular;kitten;cat;Cochlear Nerve;Auditory Pathways;Auditory Cortex/physiology;in vivo}, Mesh = {Acoustic Stimulation; Action Potentials; Aging; Animals; Animals, Newborn; Cats; Data Interpretation, Statistical; Electrocardiography; Electrophysiology; Hearing; Models, Neurological; Neurons; Poisson Distribution; Spiral Ganglion; Terminology as Topic}, Month = {Oct}, Number = {4}, Pages = {1898-908}, Pmc = {PMC2234389}, pmid = {17686914}, Pst = {ppublish}, Title = {Spontaneous discharge patterns in cochlear spiral ganglion cells before the onset of hearing in cats}, Volume = {98}, Year = {2007}, url = {papers/Jones_JNeurophysiol2007a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00472.2007}} @article{Jones:2001, Abstract = {This study examined the nature of spontaneous discharge patterns in cochlear ganglion cells in embryonic day 13 (E13) to early E17 chicken embryos (stages 39-43). Neural recordings were made with glass micropipettes. No sound-driven activity was seen for the youngest embryos (maximum intensity 107 dB sound pressure level). Ganglion cells were labeled with biotinylated dextran amine in four embryos. In two animals, primary afferents projected to hair cells in the middle region along the length of the basilar papilla in which, in one cell, the terminals occupied a neural transverse position and, in the other, a more abneural location. Statoacoustic ganglion cells showing no spontaneous activity were seen for the first time in the chicken. The proportion of "silent" cells was largest at the youngest stages (stage 39, 67\%). In active cells, mean spontaneous discharge rates [9.4 +/- 10.4 spikes (Sp)/sec; n = 44] were lower than rates for older embryos (19 +/- 17 Sp/sec) (Jones and Jones, 2000). Embryos at stages 39-41 evidenced even lower rates (4.2 +/- 5.0 Sp/sec). The most salient feature of spontaneous activity for stages 39-43 was a bursting discharge pattern in >75\% of active neurons (33 of 44). Moreover, in 55\% of these cells, there was a clear, slow, rhythmic bursting pattern. The proportion of cells showing rhythmic bursting was greatest at the youngest stages (39-42) and decreased to <30\% at stage 43. Rate of bursting ranged from 1 to 54 bursts per minute. The presence of rhythmic bursting in cochlear ganglion cells at E13-E17 provides an explanation for the existence of such patterns in central auditory relays. The bursting patterns may serve as a patterning signal for central synaptic refinements in the auditory system during development.}, Author = {Jones, T A and Jones, S M and Paggett, K C}, Date-Added = {2011-03-13 22:15:22 -0400}, Date-Modified = {2011-03-17 15:20:59 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity;21 Activity-development;21 Neurophysiology;Auditory Pathways;Cochlear Nerve;Embryo and Fetal Development;Chick Embryo}, Mesh = {Acoustic Stimulation; Action Potentials; Afferent Pathways; Animals; Biotin; Cell Count; Chick Embryo; Dextrans; Electric Stimulation; Hair Cells, Auditory; Heart Rate; Neurons; Reaction Time; Spiral Ganglion}, Month = {Oct}, Number = {20}, Pages = {8129-35}, pmid = {11588185}, Pst = {ppublish}, Title = {Primordial rhythmic bursting in embryonic cochlear ganglion cells}, Volume = {21}, Year = {2001}, url = {papers/Jones_JNeurosci2001.pdf}} @article{Gummer:1994, Abstract = {Is patterned neural activity in immature, prefunctioning sensory systems a general phenomenon? Such patterning has been found in the prenatal visual and somatosensory systems. We have now identified patterning in the immature auditory system of a prehearing mammal, the tammar wallaby. Neurones recorded in vivo from the eighth nerve and cochlear nucleus at pouch days 94-122 discharged in bursts with rhythmic inter-spike intervals. Our findings are applied to the argument that neural activity is vital to sensory development.}, Author = {Gummer, A W and Mark, R F}, Date-Added = {2011-03-13 22:13:03 -0400}, Date-Modified = {2011-03-13 22:13:42 -0400}, Journal = {Neuroreport}, Journal-Full = {Neuroreport}, Keywords = {Spontaneous activity;21 Activity-development;21 Neurophysiology;Auditory Pathways;development}, Mesh = {Acoustic Stimulation; Animals; Brain Stem; Cochlear Nucleus; Electrodes, Implanted; Evoked Potentials, Auditory, Brain Stem; Hearing; Macropodidae; Neurons; Neurons, Afferent; Vestibulocochlear Nerve}, Month = {Feb}, Number = {6}, Pages = {685-8}, pmid = {8199338}, Pst = {ppublish}, Title = {Patterned neural activity in brain stem auditory areas of a prehearing mammal, the tammar wallaby (Macropus eugenii)}, Volume = {5}, Year = {1994}, url = {papers/Gummer_Neuroreport1994.pdf}} @article{Tritsch:2007, Abstract = {Spontaneous activity in the developing auditory system is required for neuronal survival as well as the refinement and maintenance of tonotopic maps in the brain. However, the mechanisms responsible for initiating auditory nerve firing in the absence of sound have not been determined. Here we show that supporting cells in the developing rat cochlea spontaneously release ATP, which causes nearby inner hair cells to depolarize and release glutamate, triggering discrete bursts of action potentials in primary auditory neurons. This endogenous, ATP-mediated signalling synchronizes the output of neighbouring inner hair cells, which may help refine tonotopic maps in the brain. Spontaneous ATP-dependent signalling rapidly subsides after the onset of hearing, thereby preventing this experience-independent activity from interfering with accurate encoding of sound. These data indicate that supporting cells in the organ of Corti initiate electrical activity in auditory nerves before hearing, pointing to an essential role for peripheral, non-sensory cells in the development of central auditory pathways.}, Author = {Tritsch, Nicolas X and Yi, Eunyoung and Gale, Jonathan E and Glowatzki, Elisabeth and Bergles, Dwight E}, Date-Added = {2011-03-13 22:10:26 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Spontaneous activity;21 Activity-development;structural remodeling;development;Synaptic Transmission;synapse formation;refinement;Auditory Pathways;tonotopy;21 Neurophysiology;frontiers review;retinal wave paper;Technique;optical physiology;optical imaging;intrinsic signal;in vitro;rat}, Mesh = {Action Potentials; Adenosine Triphosphate; Animals; Auditory Pathways; Auditory Perception; Calcium; Cell Shape; Hair Cells, Auditory; Hearing; Rats; Rats, Sprague-Dawley; Time Factors}, Month = {Nov}, Number = {7166}, Pages = {50-5}, pmid = {17972875}, Pst = {ppublish}, Title = {The origin of spontaneous activity in the developing auditory system}, Volume = {450}, Year = {2007}, url = {papers/Tritsch_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06233}} @article{Watt:2009, Abstract = {Correlated network activity is important in the development of many neural circuits. Purkinje cells are among the first neurons to populate the cerebellar cortex, where they sprout exuberant axon collaterals. We used multiple patch-clamp recordings targeted with two-photon microscopy to characterize monosynaptic connections between the Purkinje cells of juvenile mice. We found that Purkinje cell axon collaterals projected asymmetrically in the sagittal plane, directed away from the lobule apex. On the basis of our anatomical and physiological characterization of this connection, we constructed a network model that robustly generated waves of activity that traveled along chains of connected Purkinje cells. Consistent with the model, we observed traveling waves of activity in Purkinje cells in sagittal slices from young mice that require GABA(A) receptor-mediated transmission and intact Purkinje cell axon collaterals. These traveling waves are absent in adult mice, suggesting they have a developmental role in wiring the cerebellar cortical microcircuit.}, Author = {Watt, Alanna J and Cuntz, Hermann and Mori, Masahiro and Nusser, Zoltan and Sj{\"o}str{\"o}m, P Jesper and H{\"a}usser, Michael}, Date-Added = {2011-03-13 22:03:25 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Spontaneous activity;21 Activity-development;calcium imaging;optical physiology;optical imaging;Patch-Clamp Techniques;Technique;Cerebellar Cortex;in vitro;Multiphoton;microscopy;retinal wave paper;frontiers review}, Mesh = {Action Potentials; Age Factors; Animals; Animals, Newborn; Axons; Biophysics; Cerebellar Cortex; Computer Simulation; Electric Stimulation; GABA Antagonists; Glutamate Decarboxylase; Green Fluorescent Proteins; Lysine; Mice; Mice, Transgenic; Microscopy, Confocal; Neural Networks (Computer); Patch-Clamp Techniques; Purkinje Cells; Pyridazines; Synapses; Synaptic Potentials; tau Proteins}, Month = {Apr}, Number = {4}, Pages = {463-73}, Pmc = {PMC2912499}, pmid = {19287389}, Pst = {ppublish}, Title = {Traveling waves in developing cerebellar cortex mediated by asymmetrical Purkinje cell connectivity}, Volume = {12}, Year = {2009}, url = {papers/Watt_NatNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2285}} @article{Rockhill:2009, Abstract = {Central nervous system (CNS) development depends upon spontaneous activity (SA) to establish networks. We have discovered that the mouse midbrain has SA expressed most robustly at embryonic day (E) 12.5. SA propagation in the midbrain originates in midline serotonergic cell bodies contained within the adjacent hindbrain and then passes through the isthmus along ventral midline serotonergic axons. Once within the midbrain, the wave bifurcates laterally along the isthmic border and then propagates rostrally. Along this trajectory, it is carried by a combination of GABAergic and cholinergic neurons. Removing the hindbrain eliminates SA in the midbrain. Thus, SA in the embryonic midbrain arises from a single identified pacemaker in a separate brain structure, which drives SA waves across both regions of the developing CNS. The midbrain can self-initiate activity upon removal of the hindbrain, but only with pharmacological manipulations that increase excitability. Under these conditions, new initiation foci within the midbrain become active. Anatomical analysis of the development of the serotonergic axons that carry SA from the hindbrain to the midbrain indicates that their increasing elongation during development may control the onset of SA in the midbrain.}, Author = {Rockhill, Wendy and Kirkman, Jennifer L and Bosma, Martha M}, Date-Added = {2011-03-13 21:58:50 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Dev Neurobiol}, Journal-Full = {Developmental neurobiology}, Keywords = {midbrain;hindbrain;Spontaneous activity;development;mouse;Embryonic and Fetal Development;calcium imaging;21 Activity-development;21 Neurophysiology;in vitro;optical physiology;optical imaging}, Mesh = {Action Potentials; Age Factors; Animals; Bicuculline; Calcium; Choline O-Acetyltransferase; Embryo, Mammalian; Glutamate Decarboxylase; Image Processing, Computer-Assisted; Immunohistochemistry; Mesencephalon; Mice; Nerve Net; Neurons; Picrotoxin; Rhombencephalon; Serotonin; Tyrosine 3-Monooxygenase; gamma-Aminobutyric Acid}, Month = {Sep}, Number = {11}, Pages = {689-704}, pmid = {19449313}, Pst = {ppublish}, Title = {Spontaneous activity in the developing mouse midbrain driven by an external pacemaker}, Volume = {69}, Year = {2009}, url = {papers/Rockhill_DevNeurobiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dneu.20725}} @article{Blankenship:2010, Abstract = {Patterned, spontaneous activity occurs in many developing neural circuits, including the retina, the cochlea, the spinal cord, the cerebellum and the hippocampus, where it provides signals that are important for the development of neurons and their connections. Despite there being differences in adult architecture and output across these various circuits, the patterns of spontaneous network activity and the mechanisms that generate it are remarkably similar. The mechanisms can include a depolarizing action of GABA (gamma-aminobutyric acid), transient synaptic connections, extrasynaptic transmission, gap junction coupling and the presence of pacemaker-like neurons. Interestingly, spontaneous activity is robust; if one element of a circuit is disrupted another will generate similar activity. This research suggests that developing neural circuits exhibit transient and tunable features that maintain a source of correlated activity during crucial stages of development.}, Author = {Blankenship, Aaron G and Feller, Marla B}, Date-Added = {2011-03-13 21:22:36 -0400}, Date-Modified = {2013-05-21 20:36:03 +0000}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {Spontaneous activity;review;21 Activity-development;structural remodeling;experience dependent plasticity;visual system;retinal wave paper;frontiers review;circuitry;network;evolutionary dynamics;connectivity;development; retinal wave paper; currOpinRvw}, Mesh = {Animals; Homeostasis; Humans; Models, Biological; Nerve Net; Neural Pathways; Neurons; Signal Transduction; Synapses; gamma-Aminobutyric Acid}, Month = {Jan}, Number = {1}, Pages = {18-29}, Pmc = {PMC2902252}, pmid = {19953103}, Pst = {ppublish}, Title = {Mechanisms underlying spontaneous patterned activity in developing neural circuits}, Volume = {11}, Year = {2010}, url = {papers/Blankenship_NatRevNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2759}} @article{Hooks:2008, Abstract = {In the mammalian visual system, sensory experience is widely thought to sculpt cortical circuits during a precise critical period. In contrast, subcortical regions, such as the thalamus, were thought to develop at earlier ages in a vision-independent manner. Recent studies at the retinogeniculate synapse, however, have demonstrated an influence of vision on the formation of synaptic circuits in the thalamus. In mice, dark rearing from birth does not alter normal developmental maturation of the connection between retina and thalamus. However, deprivation 20 d after birth [postnatal day 20 (p20)] resulted in dramatic weakening of synaptic strength and an increase in the number of retinal inputs that innervate a thalamic relay neuron. Here, by quantifying changes in synaptic strength and connectivity in response to different time windows of deprivation, we find that several days of vision after eye opening is necessary for triggering experience-dependent plasticity. Shorter periods of visual experience do not permit similar experience-dependent synaptic reorganization. Furthermore, changes in connectivity are rapidly reversible simply by restoring normal vision. However, similar plasticity did not occur when shifting the onset of deprivation to p25. Although synapses still weakened, recruitment of additional retinal inputs no longer occurred. Therefore, synaptic circuits in the visual thalamus are unexpectedly malleable during a late developmental period, after the time when normal synapse elimination and pruning has occurred. This thalamic sensitive period overlaps temporally with experience-dependent changes in the cortex, suggesting that subcortical plasticity may influence cortical responses to sensory experience.}, Author = {Hooks, Bryan M and Chen, Chinfei}, Date-Added = {2011-03-13 21:16:08 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;Sensory Deprivation;visual system;LGN;retina;plasticity;experience dependent plasticity;21 Neurophysiology;activity manipulation;development;Synaptic Transmission;Synapses;refinement;synapse formation}, Mesh = {Age Factors; Animals; Animals, Newborn; Critical Period (Psychology); Dose-Response Relationship, Radiation; Electric Stimulation; Excitatory Postsynaptic Potentials; Geniculate Bodies; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Neurons; Patch-Clamp Techniques; Retina; Sensory Deprivation; Synapses; Vision, Ocular; Visual Pathways}, Month = {Apr}, Number = {18}, Pages = {4807-17}, Pmc = {PMC2793334}, pmid = {18448657}, Pst = {ppublish}, Title = {Vision triggers an experience-dependent sensitive period at the retinogeniculate synapse}, Volume = {28}, Year = {2008}, url = {papers/Hooks_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4667-07.2008}} @article{Hooks:2006, Abstract = {Sensory experience and spontaneous activity play important roles in development of sensory circuits; however, their relative contributions are unclear. Here, we test the role of different forms of activity on remodeling of the mouse retinogeniculate synapse. We found that the bulk of maturation occurs without patterned sensory activity over 4 days spanning eye opening. During this early developmental period, blockade of spontaneous retinal activity by tetrodotoxin, but not visual deprivation, retarded synaptic strengthening and inhibited pruning of excess retinal afferents. Later in development, synaptic remodeling becomes sensitive to changes in visually evoked activity, but only if there has been previous visual experience. Synaptic strengthening and pruning were disrupted by visual deprivation following 1 week of vision, but not by chronic deprivation from birth. Thus, spontaneous activity is necessary to drive the bulk of synaptic refinement around the time of eye opening, while sensory experience is important for the subsequent maintenance of connections.}, Author = {Hooks, Bryan M and Chen, Chinfei}, Date-Added = {2011-03-13 19:02:22 -0400}, Date-Modified = {2013-06-27 20:40:02 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;development;structural remodeling;plasticity;experience dependent plasticity;Sensory Deprivation;Spontaneous activity;axons;refinement;mouse;visual system;LGN;retina;activity manipulation;frontiers review; currOpinRvw}, Mesh = {Action Potentials; Animals; Animals, Newborn; Cell Differentiation; Darkness; Excitatory Postsynaptic Potentials; Geniculate Bodies; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Organ Culture Techniques; Patch-Clamp Techniques; Retina; Retinal Ganglion Cells; Sensory Deprivation; Sodium Channel Blockers; Synapses; Synaptic Transmission; Vision, Ocular; Visual Pathways}, Month = {Oct}, Number = {2}, Pages = {281-91}, pmid = {17046691}, Pst = {ppublish}, Title = {Distinct roles for spontaneous and visual activity in remodeling of the retinogeniculate synapse}, Volume = {52}, Year = {2006}, url = {papers/Hooks_Neuron2006.pdf}, Bdsk-File-2 = {papers/Hooks_Neuron2006a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.07.007}} @article{Leamey:2009, Abstract = {A defining feature of the mammalian nervous system is its complex yet precise circuitry. The mechanisms which underlie the generation of neural connectivity are the topic of intense study in developmental neuroscience. The mammalian visual pathway demonstrates precise retinotopic organization in subcortical and cortical pathways, together with the alignment and matching of eye-specific projections, and sophisticated cortical circuitry that enables the extraction of features underlying vision. New approaches employing molecular-genetic analyses, transgenic mice, novel recombinant probes, and high-resolution imaging are contributing to rapid progress and a new synthesis in the field. These approaches are revealing the ways in which intrinsic patterning mechanisms act in concert with experience-dependent mechanisms to shape visual projections and circuits.}, Author = {Leamey, Catherine A and Van Wart, Audra and Sur, Mriganka}, Date-Added = {2011-03-13 12:27:56 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {21 Activity-development;Spontaneous activity;visual system;development;visual cortex;Competitive Behavior;structural remodeling;plasticity;experience dependent plasticity;axons;LGN;Superior Colliculus;optic tectum;Retina;Transgenic;mouse;Technique;review;frontiers review; currOpinRvw}, Mesh = {Animals; Cerebral Cortex; Humans; Models, Neurological; Neuronal Plasticity; Retina; Thalamus; Visual Pathways}, Month = {Apr}, Number = {2}, Pages = {181-7}, pmid = {19502049}, Pst = {ppublish}, Title = {Intrinsic patterning and experience-dependent mechanisms that generate eye-specific projections and binocular circuits in the visual pathway}, Volume = {19}, Year = {2009}, url = {papers/Leamey_CurrOpinNeurobiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2009.05.006}} @article{LeVay:1980, Author = {LeVay, S and Wiesel, T N and Hubel, D H}, Date-Added = {2011-03-13 12:04:24 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Activity-development;Spontaneous activity;structural remodeling;Visual Cortex;visual system;development;monkey;LGN;frontiers review;Classical/physiology;plasticity;experience dependent plasticity}, Mesh = {Age Factors; Animals; Dominance, Cerebral; Geniculate Bodies; Haplorhini; Macaca; Neurons; Retina; Sensory Deprivation; Visual Cortex; Visual Pathways}, Month = {May}, Number = {1}, Pages = {1-51}, pmid = {6772696}, Pst = {ppublish}, Title = {The development of ocular dominance columns in normal and visually deprived monkeys}, Volume = {191}, Year = {1980}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901910102}} @article{Hubel:1977, Author = {Hubel, D H and Wiesel, T N and LeVay, S}, Date-Added = {2011-03-13 12:01:11 -0400}, Date-Modified = {2011-03-13 12:02:54 -0400}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {21 Activity-development;Spontaneous activity;structural remodeling;Visual Cortex;visual system;development;monkey;LGN;frontiers review;Classical/physiology;plasticity;experience dependent plasticity}, Mesh = {Animals; Animals, Newborn; Autoradiography; Electrophysiology; Geniculate Bodies; Haplorhini; Macaca; Nerve Degeneration; Superior Colliculi; Vision, Ocular; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Apr}, Number = {961}, Pages = {377-409}, pmid = {19791}, Pst = {ppublish}, Title = {Plasticity of ocular dominance columns in monkey striate cortex}, Volume = {278}, Year = {1977}, url = {papers/Hubel_PhilosTransRSocLondBBiolSci1977.pdf}} @article{Redfern:1970, Abstract = {1. End-plate potentials (e.p.p.s) were recorded intracellularly from the isolated phrenic/diaphragm preparation of the rat during the first few weeks of life.2. Most e.p.p.s at birth were complex and resulted from the summation of two to four units, which could be separated by their different latencies and thresholds to stimulation of the phrenic nerve.3. The e.p.p.s became simpler during the second week of the rats' life, and by 16-18 days old the e.p.p.s consisted of single units, and resembled the e.p.p.s of adult rat muscle.4. It is proposed that the units of the e.p.p. resulted from the stimulation of separate nerve axons and that all but one of the synapses on each muscle fibre were lost during the second week of life.}, Author = {Redfern, P A}, Date-Added = {2011-03-13 11:52:03 -0400}, Date-Modified = {2011-03-13 11:56:24 -0400}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {21 Activity-development;Spinal Cord;Neuromuscular Junction;Competitive Behavior;structural remodeling;plasticity;Spontaneous activity;21 Neurophysiology;development;rat;evolutionary dynamics;frontiers review}, Mesh = {Animals; Animals, Newborn; Axons; Diaphragm}, Month = {Aug}, Number = {3}, Pages = {701-9}, Pmc = {PMC1395553}, pmid = {5499804}, Pst = {ppublish}, Title = {Neuromuscular transmission in new-born rats}, Volume = {209}, Year = {1970}, url = {papers/Redfern_JPhysiol1970.pdf}} @article{Walsh:2003, Abstract = {During development, competition between axons causes permanent removal of synaptic connections, but the dynamics have not been directly observed. Using transgenic mice that express two spectral variants of fluorescent proteins in motor axons, we imaged competing axons at developing neuromuscular junctions in vivo. Typically, one axon withdrew progressively from postsynaptic sites and the competing axon extended axonal processes to occupy those sites. In rare instances when the remaining axon did not reoccupy a site, the postsynaptic receptors rapidly disappeared. Interestingly, the progress and outcome of competition was unpredictable. Moreover, the relative areas occupied by the competitors shifted in favor of one axon and then the other. These results show synaptic competition is not always monotonic and that one axon's contraction in synaptic area is associated with another axon's expansion.}, Author = {Walsh, Mark K and Lichtman, Jeff W}, Date-Added = {2011-03-13 11:48:38 -0400}, Date-Modified = {2011-03-13 11:50:57 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;21 Neurophysiology;Competitive Behavior;Synaptic Transmission;synapse formation;development;Neuromuscular Junction;Spinal Cord;structural remodeling;Axons;frontiers review;in vivo;Technique;Imaging;Microscopy}, Mesh = {Animals; Animals, Newborn; Bacterial Proteins; Cell Communication; Cell Differentiation; Green Fluorescent Proteins; Growth Cones; Luminescent Proteins; Mice; Mice, Transgenic; Microscopy, Video; Motor Neurons; Muscle, Skeletal; Nervous System; Neuromuscular Junction; Neuronal Plasticity; Reaction Time; Receptors, Cholinergic}, Month = {Jan}, Number = {1}, Pages = {67-73}, pmid = {12526773}, Pst = {ppublish}, Title = {In vivo time-lapse imaging of synaptic takeover associated with naturally occurring synapse elimination}, Volume = {37}, Year = {2003}, url = {papers/Walsh_Neuron2003.pdf}} @article{Sanes:1999, Abstract = {We describe the formation, maturation, elimination, maintenance, and regeneration of vertebrate neuromuscular junctions (NMJs), the best studied of all synapses. The NMJ forms in a series of steps that involve the exchange of signals among its three cellular components--nerve terminal, muscle fiber, and Schwann cell. Although essentially any motor axon can form NMJs with any muscle fiber, an additional set of cues biases synapse formation in favor of appropriate partners. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling. NMJs regenerate following damage to nerve or muscle, but this process differs in fundamental ways from embryonic synaptogenesis. Finally, we consider the extent to which the NMJ is a suitable model for development of neuron-neuron synapses.}, Author = {Sanes, J R and Lichtman, J W}, Date-Added = {2011-03-13 11:45:15 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {21 Activity-development;Spontaneous activity;review;Spinal Cord;Neuromuscular Junction;Competitive Behavior;synapse formation;Synaptic Transmission;structural remodeling;connectivity;frontiers review}, Mesh = {Animals; Glycoproteins; Nerve Regeneration; Neuregulins; Neuromuscular Junction; Presynaptic Terminals; Signal Transduction; Synapses; Transcription, Genetic; Vertebrates}, Pages = {389-442}, pmid = {10202544}, Pst = {ppublish}, Title = {Development of the vertebrate neuromuscular junction}, Volume = {22}, Year = {1999}, url = {papers/Sanes_AnnuRevNeurosci1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.22.1.389}} @article{Verhage:2000, Abstract = {Brain function requires precisely orchestrated connectivity between neurons. Establishment of these connections is believed to require signals secreted from outgrowing axons, followed by synapse formation between selected neurons. Deletion of a single protein, Munc18-1, in mice leads to a complete loss of neurotransmitter secretion from synaptic vesicles throughout development. However, this does not prevent normal brain assembly, including formation of layered structures, fiber pathways, and morphologically defined synapses. After assembly is completed, neurons undergo apoptosis, leading to widespread neurodegeneration. Thus, synaptic connectivity does not depend on neurotransmitter secretion, but its maintenance does. Neurotransmitter secretion probably functions to validate already established synaptic connections.}, Author = {Verhage, M and Maia, A S and Plomp, J J and Brussaard, A B and Heeroma, J H and Vermeer, H and Toonen, R F and Hammer, R E and van den Berg, T K and Missler, M and Geuze, H J and S{\"u}dhof, T C}, Date-Added = {2011-03-13 11:12:07 -0400}, Date-Modified = {2012-11-12 22:07:47 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Activity-development;development;21 Neurophysiology;mouse;Transgenic;activity manipulation;Cerebral Cortex;Hippocampus;Spontaneous activity;Synapses;synapse formation;Synaptic Transmission;frontiers review;Technique; Structure-Activity Relationship; Classical}, Mesh = {Animals; Apoptosis; Brain; Cell Differentiation; Cell Division; Gene Deletion; Growth Cones; Mice; Mice, Knockout; Munc18 Proteins; Nerve Degeneration; Nerve Tissue Proteins; Neural Pathways; Neuromuscular Junction; Neurons; Neurotransmitter Agents; Patch-Clamp Techniques; Synapses; Synaptic Transmission; Synaptic Vesicles; Vesicular Transport Proteins}, Month = {Feb}, Number = {5454}, Pages = {864-9}, pmid = {10657302}, Pst = {ppublish}, Title = {Synaptic assembly of the brain in the absence of neurotransmitter secretion}, Volume = {287}, Year = {2000}, url = {papers/Verhage_Science2000.pdf}} @article{Varoqueaux:2002, Abstract = {Synaptic vesicles must be primed to fusion competence before they can fuse with the plasma membrane in response to increased intracellular Ca2+ levels. The presynaptic active zone protein Munc13-1 is essential for priming of glutamatergic synaptic vesicles in hippocampal neurons. However, a small subpopulation of synapses in any given glutamatergic nerve cell as well as all gamma-aminobutyratergic (GABAergic) synapses are largely independent of Munc13-1. We show here that Munc13-2, the only Munc13 isoform coexpressed with Munc13-1 in hippocampus, is responsible for vesicle priming in Munc13-1 independent hippocampal synapses. Neurons lacking both Munc13-1 and Munc13-2 show neither evoked nor spontaneous release events, yet form normal numbers of synapses with typical ultrastructural features. Thus, the two Munc13 isoforms are completely redundant in GABAergic cells whereas glutamatergic neurons form two types of synapses, one of which is solely Munc13-1 dependent and lacks Munc13-2 whereas the other type employs Munc13-2 as priming factor. We conclude that Munc13-mediated vesicle priming is not a transmitter specific phenomenon but rather a general and essential feature of multiple fast neurotransmitter systems, and that synaptogenesis during development is not dependent on synaptic secretory activity.}, Author = {Varoqueaux, Frederique and Sigler, Albrecht and Rhee, Jeong-Seop and Brose, Nils and Enk, Carsten and Reim, Kerstin and Rosenmund, Christian}, Date-Added = {2011-03-13 11:07:05 -0400}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Activity-development;development;21 Neurophysiology;mouse;Transgenic;activity manipulation;Cerebral Cortex;Hippocampus;Spontaneous activity;Synapses;synapse formation;Synaptic Transmission;frontiers review}, Mesh = {Animals; Blotting, Western; Endocytosis; Hippocampus; Intracellular Signaling Peptides and Proteins; Mice; Mice, Knockout; Microscopy, Electron; Molecular Sequence Data; Nerve Tissue Proteins; Synapses; Synaptic Transmission}, Month = {Jun}, Number = {13}, Pages = {9037-42}, Pmc = {PMC124419}, pmid = {12070347}, Pst = {ppublish}, Title = {Total arrest of spontaneous and evoked synaptic transmission but normal synaptogenesis in the absence of Munc13-mediated vesicle priming}, Volume = {99}, Year = {2002}, url = {papers/Varoqueaux_ProcNatlAcadSciUSA2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.122623799}} @article{Diez-Garcia:2007, Abstract = {Genetically encoded fluorescent calcium indicator proteins provide the potential to monitor activity from genetically specified target cells without a need for single cell resolution. Here we report the use of transgenic mice expressing the fluorescent calcium indicator protein GCaMP2 in cerebellar granule cells to image parallel fiber activity transcranially in vivo. We demonstrated reliable measurements of calcium transients from beams of parallel fibers in response to electrical stimulation in the molecular layer through the intact skull. These parallel fiber calcium transients differed from intrinsic postsynaptic autofluorescence signals in their faster kinetics and resistance to blockers of synaptic transmission. Finally, we used 2P laser-scanning microscopy to demonstrate reliable measurements of calcium transients from beams of parallel fibers at high spatial resolution in living mice. We expect that genetically targeted fluorescent calcium indicator proteins along with optical imaging techniques will be instrumental for the construction of macroscopic and microscopic maps of the function of specific brain circuits.}, Author = {D{\'\i}ez-Garc{\'\i}a, Javier and Akemann, Walther and Kn{\"o}pfel, Thomas}, Date-Added = {2011-03-12 09:42:28 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Keywords = {optical physiology;optical imaging;calcium imaging;calcium sensor;Technique;frontiers review;function;Cerebellar Cortex;Transgenic;mouse;21 Neurophysiology;Imaging;in vivo;microscopy;Multiphoton}, Mesh = {Animals; Calcium; Calcium Signaling; Cerebellum; Gene Targeting; Mice; Mice, Transgenic; Microscopy, Fluorescence, Multiphoton; Neurons; Shaw Potassium Channels}, Month = {Feb}, Number = {3}, Pages = {859-69}, pmid = {17161628}, Pst = {ppublish}, Title = {In vivo calcium imaging from genetically specified target cells in mouse cerebellum}, Volume = {34}, Year = {2007}, url = {papers/Díez-García_Neuroimage2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2006.10.021}} @article{Fletcher:2009, Abstract = {Olfactory glomeruli are the loci where the first odor-representation map emerges. The glomerular layer comprises exquisite local synaptic circuits for the processing of olfactory coding patterns immediately after their emergence. To understand how an odor map is transferred from afferent terminals to postsynaptic dendrites, it is essential to directly monitor the odor-evoked glomerular postsynaptic activity patterns. Here we report the use of a transgenic mouse expressing a Ca(2+)-sensitive green fluorescence protein (GCaMP2) under a Kv3.1 potassium-channel promoter. Immunostaining revealed that GCaMP2 was specifically expressed in mitral and tufted cells and a subpopulation of juxtaglomerular cells but not in olfactory nerve terminals. Both in vitro and in vivo imaging combined with glutamate receptor pharmacology confirmed that odor maps reported by GCaMP2 were of a postsynaptic origin. These mice thus provided an unprecedented opportunity to analyze the spatial activity pattern reflecting purely postsynaptic olfactory codes. The odor-evoked GCaMP2 signal had both focal and diffuse spatial components. The focalized hot spots corresponded to individually activated glomeruli. In GCaMP2-reported postsynaptic odor maps, different odorants activated distinct but overlapping sets of glomeruli. Increasing odor concentration increased both individual glomerular response amplitude and the total number of activated glomeruli. Furthermore, the GCaMP2 response displayed a fast time course that enabled us to analyze the temporal dynamics of odor maps over consecutive sniff cycles. In summary, with cell-specific targeting of a genetically encoded Ca(2+) indicator, we have successfully isolated and characterized an intermediate level of odor representation between olfactory nerve input and principal mitral/tufted cell output.}, Author = {Fletcher, Max L and Masurkar, Arjun V and Xing, Junling and Imamura, Fumiaki and Xiong, Wenhui and Nagayama, Shin and Mutoh, Hiroki and Greer, Charles A and Kn{\"o}pfel, Thomas and Chen, Wei R}, Date-Added = {2011-03-12 09:33:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {optical physiology;optical imaging;calcium imaging;calcium sensor;Technique;frontiers review;function;Olfactory Bulb;Transgenic;mouse;21 Neurophysiology;Imaging;in vivo;microscopy}, Mesh = {2-Amino-5-phosphonovalerate; 6-Cyano-7-nitroquinoxaline-2,3-dione; Animals; Calcium; Dendrites; Electric Stimulation; Excitatory Amino Acid Antagonists; Green Fluorescent Proteins; Kinetics; Membrane Potentials; Mice; Mice, Transgenic; Neurons; Odors; Olfactory Bulb; Olfactory Nerve; Olfactory Perception; Physical Stimulation; Respiration; Synapses}, Month = {Aug}, Number = {2}, Pages = {817-30}, Pmc = {PMC2724327}, pmid = {19474178}, Pst = {ppublish}, Title = {Optical imaging of postsynaptic odor representation in the glomerular layer of the mouse olfactory bulb}, Volume = {102}, Year = {2009}, url = {papers/Fletcher_JNeurophysiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00020.2009}} @article{OConnor:2010, Abstract = {Classical studies have related the spiking of selected neocortical neurons to behavior, but little is known about activity sampled from the entire neural population. We recorded from neurons selected independent of spiking, using cell-attached recordings and two-photon calcium imaging, in the barrel cortex of mice performing an object localization task. Spike rates varied across neurons, from silence to >60 Hz. Responses were diverse, with some neurons showing large increases in spike rate when whiskers contacted the object. Nearly half the neurons discriminated object location; a small fraction of neurons discriminated perfectly. More active neurons were more discriminative. Layer (L) 4 and L5 contained the highest fractions of discriminating neurons (∼63\% and 79\%, respectively), but a few L2/3 neurons were also highly discriminating. Approximately 13,000 spikes per activated barrel column were available to mice for decision making. Coding of object location in the barrel cortex is therefore highly redundant.}, Author = {O'Connor, Daniel H and Peron, Simon P and Huber, Daniel and Svoboda, Karel}, Date-Added = {2011-03-11 16:20:25 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology;optical imaging;Imaging;calcium imaging;calcium sensor;Somatosensory Cortex;Neocortex;Multiphoton;microscopy;in vivo;Behavior}, Mesh = {Action Potentials; Afferent Pathways; Animals; Behavior, Animal; Brain Mapping; Calcium; Discrimination (Psychology); Male; Mice; Mice, Inbred C57BL; Models, Biological; Neurons; Physical Stimulation; ROC Curve; Somatosensory Cortex; Vibrissae}, Month = {Sep}, Number = {6}, Pages = {1048-61}, pmid = {20869600}, Pst = {ppublish}, Title = {Neural activity in barrel cortex underlying vibrissa-based object localization in mice}, Volume = {67}, Year = {2010}, url = {papers/O'Connor_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.08.026}} @article{Nagai:2004, Abstract = {Fluorescence resonance energy transfer (FRET) technology has been used to develop genetically encoded fluorescent indicators for various cellular functions. Although most indicators have cyan- and yellow-emitting fluorescent proteins (CFP and YFP) as FRET donor and acceptor, their poor dynamic range often prevents detection of subtle but significant signals. Here, we optimized the relative orientation of the two chromophores in the Ca(2+) indicator, yellow cameleon (YC), by fusing YFP at different angles. We generated circularly permuted YFPs (cpYFPs) that showed efficient maturation and acid stability. One of the cpYFPs incorporated in YC absorbs a great amount of excited energy from CFP in its Ca(2+)-saturated form, thereby increasing the Ca(2+)-dependent change in the ratio of YFP/CFP by nearly 600\%. Both in cultured cells and in the nervous system of transgenic mice, the new YC enables visualization of subcellular Ca(2+) dynamics with better spatial and temporal resolution than before. Our study provides an important guide for the development and improvement of indicators using GFP-based FRET.}, Author = {Nagai, Takeharu and Yamada, Shuichi and Tominaga, Takashi and Ichikawa, Michinori and Miyawaki, Atsushi}, Date-Added = {2011-03-11 15:20:41 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {optical imaging;calcium imaging;calcium sensor;optical physiology;frontiers review;imaging;Technique}, Mesh = {Animals; Bacterial Proteins; Calcium; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Hela Cells; Humans; Luminescent Proteins; Mice; Microscopy, Fluorescence; Models, Molecular; Molecular Sequence Data; Protein Conformation}, Month = {Jul}, Number = {29}, Pages = {10554-9}, Pmc = {PMC490022}, pmid = {15247428}, Pst = {ppublish}, Title = {Expanded dynamic range of fluorescent indicators for Ca(2+) by circularly permuted yellow fluorescent proteins}, Volume = {101}, Year = {2004}, url = {papers/Nagai_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0400417101}} @article{Kuchibhotla:2008, Abstract = {Alzheimer's disease is characterized by the deposition of senile plaques and progressive dementia. The molecular mechanisms that couple plaque deposition to neural system failure, however, are unknown. Using transgenic mouse models of AD together with multiphoton imaging, we measured neuronal calcium in individual neurites and spines in vivo using the genetically encoded calcium indicator Yellow Cameleon 3.6. Quantitative imaging revealed elevated [Ca(2+)]i (calcium overload) in approximately 20\% of neurites in APP mice with cortical plaques, compared to less than 5\% in wild-type mice, PS1 mutant mice, or young APP mice (animals without cortical plaques). Calcium overload depended on the existence and proximity to plaques. The downstream consequences included the loss of spinodendritic calcium compartmentalization (critical for synaptic integration) and a distortion of neuritic morphologies mediated, in part, by the phosphatase calcineurin. Together, these data demonstrate that senile plaques impair neuritic calcium homeostasis in vivo and result in the structural and functional disruption of neuronal networks.}, Author = {Kuchibhotla, Kishore V and Goldman, Samuel T and Lattarulo, Carli R and Wu, Hai-Yan and Hyman, Bradley T and Bacskai, Brian J}, Date-Added = {2011-03-11 15:02:31 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology;optical imaging;imaging;Neurophysiology;Calcium;calcium imaging;calcium sensor;glia;Astrocytes;neocortex;Technique;neurological disorder;Alzheimer Disease;frontiers review}, Mesh = {Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; CHO Cells; Calcium; Cells, Cultured; Chickens; Cricetinae; Cricetulus; Homeostasis; Humans; Mice; Mice, Transgenic; Nerve Net; Neurons; Plaque, Amyloid}, Month = {Jul}, Number = {2}, Pages = {214-25}, Pmc = {PMC2578820}, pmid = {18667150}, Pst = {ppublish}, Title = {Abeta plaques lead to aberrant regulation of calcium homeostasis in vivo resulting in structural and functional disruption of neuronal networks}, Volume = {59}, Year = {2008}, url = {papers/Kuchibhotla_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.06.008}} @article{Barth:2004, Abstract = {Identifying the cells and circuits that underlie perception, behavior, and learning is a central goal of contemporary neuroscience. Although techniques such as lesion analysis, functional magnetic resonance imaging, 2-deoxyglucose studies, and induction of gene expression have been helpful in determining the brain areas responsible for particular functions, these methods are technically limited. Currently, there is no method that allows for the identification and electrophysiological characterization of individual neurons that are associated with a particular function in living tissue. We developed a strain of transgenic mice in which the expression of the green fluorescent protein (GFP) is controlled by the promoter of the activity-dependent gene c-fos. These mice enable an in vivo or ex vivo characterization of the cells and synapses that are activated by particular pharmacological and behavioral manipulations. Cortical and subcortical fosGFP expression could be induced in a regionally restricted manner after specific activation of neuronal ensembles. Using the fosGFP mice to identify discrete cortical areas, we found that neurons in sensory-spared areas rapidly regulate action potential threshold and spike frequency to decrease excitability. This method will enhance our ability to study the way neuronal networks are activated and changed by both experience and pharmacological manipulations. In addition, because activated neurons can be functionally characterized, this tool may enable the development of better pharmaceuticals that directly affect the neurons involved in disease states.}, Author = {Barth, Alison L and Gerkin, Richard C and Dean, Kathleen L}, Date-Added = {2011-03-10 23:28:44 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Technique;Immediate-Early;genes;Imaging;microscopy;21 Neurophysiology;21 Activity-development;experience dependent plasticity;frontiers review}, Mesh = {Action Potentials; Animals; Antipsychotic Agents; Brain; Clozapine; Dehydration; Genes, fos; Green Fluorescent Proteins; Immunohistochemistry; Kinetics; Luminescent Agents; Mice; Mice, Transgenic; Neurons; Paraventricular Hypothalamic Nucleus; Recombinant Fusion Proteins; Somatosensory Cortex}, Month = {Jul}, Number = {29}, Pages = {6466-75}, pmid = {15269256}, Pst = {ppublish}, Title = {Alteration of neuronal firing properties after in vivo experience in a FosGFP transgenic mouse}, Volume = {24}, Year = {2004}, url = {papers/Barth_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4737-03.2004}} @article{Schroder-Lang:2007, Abstract = {The flagellate Euglena gracilis contains a photoactivated adenylyl cyclase (PAC), consisting of the flavoproteins PACalpha and PACbeta. Here we report functional expression of PACs in Xenopus laevis oocytes, HEK293 cells and in Drosophila melanogaster, where neuronal expression yields light-induced changes in behavior. The activity of PACs is strongly and reversibly enhanced by blue light, providing a powerful tool for light-induced manipulation of cAMP in animal cells.}, Author = {Schr{\"o}der-Lang, Saskia and Schw{\"a}rzel, Martin and Seifert, Reinhard and Str{\"u}nker, Timo and Kateriya, Suneel and Looser, Jens and Watanabe, Masakatsu and Kaupp, U Benjamin and Hegemann, Peter and Nagel, Georg}, Date-Added = {2011-03-10 23:13:00 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {Technique;activity manipulation;Cyclic AMP;21 Activity-development;Photic Stimulation;frontiers review}, Mesh = {Adenylate Cyclase; Animals; Animals, Genetically Modified; Cell Line; Cyclic AMP; Drosophila melanogaster; Enzyme Activation; Euglena gracilis; Gene Transfer Techniques; Humans; Light; Time Factors; Xenopus laevis}, Month = {Jan}, Number = {1}, Pages = {39-42}, pmid = {17128267}, Pst = {ppublish}, Title = {Fast manipulation of cellular cAMP level by light in vivo}, Volume = {4}, Year = {2007}, url = {papers/Schröder-Lang_NatMethods2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth975}} @article{Boyden:2005, Abstract = {Temporally precise, noninvasive control of activity in well-defined neuronal populations is a long-sought goal of systems neuroscience. We adapted for this purpose the naturally occurring algal protein Channelrhodopsin-2, a rapidly gated light-sensitive cation channel, by using lentiviral gene delivery in combination with high-speed optical switching to photostimulate mammalian neurons. We demonstrate reliable, millisecond-timescale control of neuronal spiking, as well as control of excitatory and inhibitory synaptic transmission. This technology allows the use of light to alter neural processing at the level of single spikes and synaptic events, yielding a widely applicable tool for neuroscientists and biomedical engineers.}, Author = {Boyden, Edward S and Zhang, Feng and Bamberg, Ernst and Nagel, Georg and Deisseroth, Karl}, Date-Added = {2011-03-10 22:57:32 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {activity manipulation;Technique;Photoreceptors;21 Circuit structure-function;21 Neurophysiology;Gene Transfer Techniques;viral gene transfer;frontiers review}, Mesh = {Action Potentials; Algal Proteins; Animals; Animals, Newborn; Cells, Cultured; Dose-Response Relationship, Radiation; Electric Stimulation; Electrophysiology; Excitatory Amino Acid Antagonists; GABA Antagonists; Green Fluorescent Proteins; Hippocampus; Ion Channel Gating; Ion Channels; Neural Inhibition; Neurons; Optics and Photonics; Photobiology; Pyridazines; Quinoxalines; Rats; Rats, Sprague-Dawley; Reaction Time; Reproducibility of Results; Rhodopsin; Synaptic Transmission; Time Factors; Transfection}, Month = {Sep}, Number = {9}, Pages = {1263-8}, pmid = {16116447}, Pst = {ppublish}, Title = {Millisecond-timescale, genetically targeted optical control of neural activity}, Volume = {8}, Year = {2005}, url = {papers/Boyden_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1525}} @article{Li:2005a, Abstract = {Techniques for fast noninvasive control of neuronal excitability will be of major importance for analyzing and understanding neuronal networks and animal behavior. To develop these tools we demonstrated that two light-activated signaling proteins, vertebrate rat rhodopsin 4 (RO4) and the green algae channelrhodospin 2 (ChR2), could be used to control neuronal excitability and modulate synaptic transmission. Vertebrate rhodopsin couples to the Gi/o, pertussis toxin-sensitive pathway to allow modulation of G protein-gated inward rectifying potassium channels and voltage-gated Ca2+ channels. Light-mediated activation of RO4 in cultured hippocampal neurons reduces neuronal firing within ms by hyperpolarization of the somato-dendritic membrane and when activated at presynaptic sites modulates synaptic transmission and paired-pulse facilitation. In contrast, somato-dendritic activation of ChR2 depolarizes neurons sufficiently to induce immediate action potentials, which precisely follow the ChR2 activation up to light stimulation frequencies of 20 Hz. To demonstrate that these constructs are useful for regulating network behavior in intact organisms, embryonic chick spinal cords were electroporated with either construct, allowing the frequency of episodes of spontaneous bursting activity, known to be important for motor circuit formation, to be precisely controlled. Thus light-activated vertebrate RO4 and green algae ChR2 allow the antagonistic control of neuronal function within ms to s in a precise, reversible, and noninvasive manner in cultured neurons and intact vertebrate spinal cords.}, Author = {Li, Xiang and Gutierrez, Davina V and Hanson, M Gartz and Han, Jing and Mark, Melanie D and Chiel, Hillel and Hegemann, Peter and Landmesser, Lynn T and Herlitze, Stefan}, Date-Added = {2011-03-10 22:53:00 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {activity manipulation;Technique;Spinal Cord;Chick Embryo;Gene Transfer Techniques;Photoreceptors;21 Activity-development;21 Circuit structure-function;frontiers review}, Mesh = {Animals; Calcium Channels; Cell Line; Chick Embryo; Chlamydomonas reinhardtii; Electrophysiology; Hippocampus; Nerve Net; Neurons; Patch-Clamp Techniques; Rats; Rhodopsin; Spinal Cord; Time Factors}, Month = {Dec}, Number = {49}, Pages = {17816-21}, Pmc = {PMC1292990}, pmid = {16306259}, Pst = {ppublish}, Title = {Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin}, Volume = {102}, Year = {2005}, url = {papers/Li_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0509030102}} @article{Kramer:2009, Abstract = {Neurobiology has entered a new era in which optical methods are challenging electrophysiological techniques for their value in measuring and manipulating neuronal activity. This change is occurring largely because of the development of new photochemical tools, some synthesized by chemists and some provided by nature. This review is focused on the three types of photochemical tools for neuronal control that have emerged in recent years. Caged neurotransmitters, including caged glutamate, are synthetic molecules that enable highly localized activation of neurotransmitter receptors in response to light. Natural photosensitive proteins, including channelrhodopsin-2 and halorhodopsin, can be exogenously expressed in neurons and enable rapid photocontrol of action potential firing. Synthetic small molecule photoswitches can bestow light-sensitivity on native or exogenously expressed proteins, including K(+) channels and glutamate receptors, allowing photocontrol of action potential firing and synaptic events. At a rapid pace, these tools are being improved and new tools are being introduced, thanks to molecular biology and synthetic chemistry. The three families of photochemical tools have different capabilities and uses, but they all share in enabling precise and noninvasive exploration of neural function with light.}, Author = {Kramer, Richard H and Fortin, Doris L and Trauner, Dirk}, Date-Added = {2011-03-10 22:38:47 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Technique;optogenetics;review;frontiers review;activity manipulation}, Mesh = {Animals; Neurons; Neurotransmitter Agents; Photic Stimulation; Photochemistry}, Month = {Oct}, Number = {5}, Pages = {544-52}, Pmc = {PMC2788492}, pmid = {19828309}, Pst = {ppublish}, Title = {New photochemical tools for controlling neuronal activity}, Volume = {19}, Year = {2009}, url = {papers/Kramer_CurrOpinNeurobiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2009.09.004}} @article{Nagel:2003, Abstract = {Microbial-type rhodopsins are found in archaea, prokaryotes, and eukaryotes. Some of them represent membrane ion transport proteins such as bacteriorhodopsin, a light-driven proton pump, or channelrhodopsin-1 (ChR1), a recently identified light-gated proton channel from the green alga Chlamydomonas reinhardtii. ChR1 and ChR2, a related microbial-type rhodopsin from C. reinhardtii, were shown to be involved in generation of photocurrents of this green alga. We demonstrate by functional expression, both in oocytes of Xenopus laevis and mammalian cells, that ChR2 is a directly light-switched cation-selective ion channel. This channel opens rapidly after absorption of a photon to generate a large permeability for monovalent and divalent cations. ChR2 desensitizes in continuous light to a smaller steady-state conductance. Recovery from desensitization is accelerated by extracellular H+ and negative membrane potential, whereas closing of the ChR2 ion channel is decelerated by intracellular H+. ChR2 is expressed mainly in C. reinhardtii under low-light conditions, suggesting involvement in photoreception in dark-adapted cells. The predicted seven-transmembrane alpha helices of ChR2 are characteristic for G protein-coupled receptors but reflect a different motif for a cation-selective ion channel. Finally, we demonstrate that ChR2 may be used to depolarize small or large cells, simply by illumination.}, Author = {Nagel, Georg and Szellas, Tanjef and Huhn, Wolfram and Kateriya, Suneel and Adeishvili, Nona and Berthold, Peter and Ollig, Doris and Hegemann, Peter and Bamberg, Ernst}, Date-Added = {2011-03-10 22:33:37 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Technique;activity manipulation;Photoreceptors;21 Neurophysiology;21 Circuit structure-function;frontiers review}, Mesh = {Algal Proteins; Animals; Cations; Cell Line; Chlamydomonas reinhardtii; Cricetinae; Female; Humans; Hydrogen-Ion Concentration; Ion Channel Gating; Ion Channels; Light; Membrane Potentials; Oocytes; Photobiology; Protozoan Proteins; Recombinant Proteins; Rhodopsin; Xenopus laevis}, Month = {Nov}, Number = {24}, Pages = {13940-5}, Pmc = {PMC283525}, pmid = {14615590}, Pst = {ppublish}, Title = {Channelrhodopsin-2, a directly light-gated cation-selective membrane channel}, Volume = {100}, Year = {2003}, url = {papers/Nagel_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1936192100}} @article{Mizuno:2010, Abstract = {Callosal projection neurons, one of the major types of projection neurons in the mammalian cerebral cortex, require neuronal activity for their axonal projections [H. Mizuno et al. (2007) J. Neurosci., 27, 6760-6770; C. L. Wang et al. (2007) J. Neurosci., 27, 11334-11342]. Here we established a method to label a few callosal axons with enhanced green fluorescent protein in the mouse cerebral cortex and examined the effect of pre-synaptic/post-synaptic neuron silencing on the morphology of individual callosal axons. Pre-synaptic/post-synaptic neurons were electrically silenced by Kir2.1 potassium channel overexpression. Single axon tracing showed that, after reaching the cortical innervation area, green fluorescent protein-labeled callosal axons underwent successive developmental stages: axon growth, branching, layer-specific targeting and arbor formation between post-natal day (P)5 and P9, and the subsequent elaboration of axon arbors between P9 and P15. Reducing pre-synaptic neuronal activity disturbed axon growth and branching before P9, as well as arbor elaboration afterwards. In contrast, silencing post-synaptic neurons disturbed axon arbor elaboration between P9 and P15. Thus, pre-synaptic neuron silencing affected significantly earlier stages of callosal projection neuron axon development than post-synaptic neuron silencing. Silencing both pre-synaptic and post-synaptic neurons impaired callosal axon projections, suggesting that certain levels of firing activity in pre-synaptic and post-synaptic neurons are required for callosal axon development. Our findings provide in-vivo evidence that pre-synaptic and post-synaptic neuronal activities play critical, and presumably differential, roles in axon growth, branching, arbor formation and elaboration during cortical axon development.}, Author = {Mizuno, Hidenobu and Hirano, Tomoo and Tagawa, Yoshiaki}, Date-Added = {2011-03-10 09:14:49 -0500}, Date-Modified = {2013-05-31 20:04:08 +0000}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {21 Activity-development;development;Neocortex;structural remodeling;plasticity;activity manipulation;frontiers review; currOpinRvw}, Mesh = {Animals; Animals, Newborn; Axons; Cell Shape; Cerebral Cortex; Corpus Callosum; Electroporation; Female; Green Fluorescent Proteins; Mice; Neural Pathways; Neurons, Efferent; Potassium Channels, Inwardly Rectifying; Pregnancy; Synaptic Transmission}, Month = {Feb}, Number = {3}, Pages = {410-24}, pmid = {20105242}, Pst = {ppublish}, Title = {Pre-synaptic and post-synaptic neuronal activity supports the axon development of callosal projection neurons during different post-natal periods in the mouse cerebral cortex}, Volume = {31}, Year = {2010}, url = {papers/Mizuno_EurJNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2009.07070.x}} @article{Wang:2007a, Abstract = {The corpus callosum is the largest commissural system in the mammalian brain, but the mechanisms underlying its development are not well understood. Here we report that neuronal activity is necessary for the normal development and maintenance of callosal projections in the mouse somatosensory cortex. We labeled a subpopulation of layer II/III callosal neurons via in utero electroporation and traced their axons in the contralateral cortex at different postnatal stages. Callosal axons displayed region- and layer-specific projection patterns within the first 2 weeks postnatally. Prenatal suppression of neuronal excitation was achieved via electroporation-induced overexpression of the inward rectifying potassium channel Kir2.1 in layer II/III cortical neurons. This resulted in abnormal callosal projections with many axons extending beyond layers II-III to terminate in layer I. Others failed to terminate at the border between the primary and secondary somatosensory cortices. Blocking synaptic transmission via expression of the tetanus toxin light chain (TeNT-LC) in these axons produced a more pronounced reduction in the projections to the border region, and the eventual disappearance of callosal projections over the entire somatosensory cortex. When Kir2.1 and TeNT-LC were coexpressed, callosal axon targeting exhibited a more severe phenotype that appeared to represent the addition of the effects produced by individual expression of Kir2.1 and TeNT-LC. These results underscore the importance of activity in regulating the developing neural connections and suggest that neuronal and synaptic activities are involved in regulating different aspects of the development of callosal projection.}, Author = {Wang, Chun-Lei and Zhang, Lei and Zhou, Yang and Zhou, Jing and Yang, Xiu-Juan and Duan, Shu-min and Xiong, Zhi-Qi and Ding, Yu-Qiang}, Date-Added = {2011-03-10 09:13:23 -0500}, Date-Modified = {2012-11-13 16:34:21 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;development;Mouse;Neocortex;structural remodeling;plasticity;frontiers review; next; toread; Grants}, Mesh = {Animals; Animals, Newborn; Corpus Callosum; Mice; Nerve Net; Somatosensory Cortex; Synaptic Transmission}, Month = {Oct}, Number = {42}, Pages = {11334-42}, pmid = {17942728}, Pst = {ppublish}, Title = {Activity-dependent development of callosal projections in the somatosensory cortex}, Volume = {27}, Year = {2007}, url = {papers/Wang_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3380-07.2007}} @article{Cao:2007, Abstract = {Activity-dependent competition that operates on branch stability or formation plays a critical role in shaping the pattern and complexity of axonal terminal arbors. In the mammalian central nervous system (CNS), the effect of activity-dependent competition on axon arborization and on the assembly of sensory maps is well established. However, the molecular pathways that modulate axonal-branch stability or formation in competitive environments remain unknown.}, Author = {Cao, Luxiang and Dhilla, Alefiya and Mukai, Jun and Blazeski, Richard and Lodovichi, Claudia and Mason, Carol A and Gogos, Joseph A}, Date-Added = {2011-03-10 09:10:19 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {21 Activity-development;development;Olfactory Bulb;molecules;genes;structural remodeling;plasticity;frontiers review}, Mesh = {Amino Acid Substitution; Animals; Axons; Brain-Derived Neurotrophic Factor; Mice; Mice, Transgenic; Neurons, Afferent; Receptor, Nerve Growth Factor; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Smell}, Month = {Jun}, Number = {11}, Pages = {911-21}, Pmc = {PMC2175069}, pmid = {17493809}, Pst = {ppublish}, Title = {Genetic modulation of BDNF signaling affects the outcome of axonal competition in vivo}, Volume = {17}, Year = {2007}, url = {papers/Cao_CurrBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2007.04.040}} @article{Yu:2004, Abstract = {We have developed a genetic approach to examine the role of spontaneous activity and synaptic release in the establishment and maintenance of an olfactory sensory map. Conditional expression of tetanus toxin light chain, a molecule that inhibits synaptic release, does not perturb targeting during development, but neurons that express this molecule in a competitive environment fail to maintain appropriate synaptic connections and disappear. Overexpression of the inward rectifying potassium channel, Kir2.1, diminishes the excitability of sensory neurons and more severely disrupts the formation of an olfactory map. These studies suggest that spontaneous neural activity is required for the establishment and maintenance of the precise connectivity inherent in an olfactory sensory map.}, Author = {Yu, C Ron and Power, Jennifer and Barnea, Gilad and O'Donnell, Sean and Brown, Hannah E V and Osborne, Joseph and Axel, Richard and Gogos, Joseph A}, Date-Added = {2011-03-10 09:08:40 -0500}, Date-Modified = {2011-03-10 09:09:18 -0500}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;Spontaneous activity;Olfactory Bulb;development;activity manipulation;in vivo;frontiers review}, Mesh = {Action Potentials; Animals; Body Patterning; Brain Mapping; Cell Differentiation; Gene Expression Regulation, Developmental; Genes, Reporter; Growth Cones; Membrane Proteins; Metalloendopeptidases; Mice; Neuronal Plasticity; Neurons, Afferent; Olfactory Bulb; Olfactory Mucosa; Olfactory Pathways; Potassium Channels, Inwardly Rectifying; Presynaptic Terminals; R-SNARE Proteins; Synaptic Transmission; Synaptophysin; Tetanus Toxin}, Month = {May}, Number = {4}, Pages = {553-66}, pmid = {15157418}, Pst = {ppublish}, Title = {Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map}, Volume = {42}, Year = {2004}, url = {papers/Yu_Neuron2004.pdf}} @article{Nikolaou:2011, Abstract = {The study of nervous system assembly has been greatly facilitated by recent advances in molecular biology and imaging techniques. These approaches are perfectly suited to young transparent zebrafish where they have allowed direct observation of neural circuit assembly in vivo. In this review will highlight a number of key studies that have applied optical and genetic techniques in zebrafish to address questions relating to axonal and dendritic arbour development, synapse assembly and neural plasticity. These experiments have demonstrated novel cellular phenomena and modes of growth that may reflect general principles governing the assembly of neural circuits. {\copyright} 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2011.}, Author = {Nikolaou, Nikolas and Meyer, Martin P}, Date-Added = {2011-03-08 20:10:39 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Dev Neurobiol}, Journal-Full = {Developmental neurobiology}, Keywords = {21 Activity-development;development;structural remodeling;activity manipulation;review;Zebrafish;frontiers review}, Month = {Jan}, pmid = {21309080}, Pst = {aheadofprint}, Title = {Imaging circuit formation in zebrafish}, Year = {2011}, url = {papers/Nikolaou_DevNeurobiol2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dneu.20874}} @article{Ben-Fredj:2010, Abstract = {In the retinotectal projection, synapses guide retinal ganglion cell (RGC) axon arbor growth by promoting branch formation and by selectively stabilizing branches. To ask whether presynaptic function is required for this dual role of synapses, we have suppressed presynaptic function in single RGCs using targeted expression of tetanus toxin light-chain fused to enhanced green fluorescent protein (TeNT-Lc:EGFP). Time-lapse imaging of singly silenced axons as they arborize in the tectum of zebrafish larvae shows that presynaptic function is not required for stabilizing branches or for generating an arbor of appropriate complexity. However, synaptic activity does regulate two distinct aspects of arbor development. First, single silenced axons fail to arrest formation of highly dynamic but short-lived filopodia that are a feature of immature axons. Second, single silenced axons fail to arrest growth of established branches and so occupy significantly larger territories in the tectum than active axons. However, if activity-suppressed axons had neighbors that were also silent, axonal arbors appeared normal in size. A similar reversal in phenotype was observed when single TeNT-Lc:EGFP axons are grown in the presence of the NMDA receptor antagonist MK801 [(+)-5-methyl-10,11- dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate]. Although expansion of arbor territory is prevented when neighbors are silent, formation of transient filopodia is not. These results suggest that synaptic activity by itself regulates filopodia formation regardless of activity in neighboring cells but that the ability to arrest growth and focusing of axonal arbors in the target is an activity-dependent, competitive process.}, Author = {Ben Fredj, Naila and Hammond, Sarah and Otsuna, Hideo and Chien, Chi-Bin and Burrone, Juan and Meyer, Martin P}, Date-Added = {2011-03-08 19:51:00 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;Technique;Zebrafish;structural remodeling;Development;activity manipulation;frontiers review}, Mesh = {Analysis of Variance; Animals; Animals, Genetically Modified; Axons; Calcium; Cells, Cultured; DNA-Binding Proteins; Dizocilpine Maleate; Embryo, Mammalian; Embryo, Nonmammalian; Excitatory Amino Acid Antagonists; Gene Expression Regulation, Developmental; Green Fluorescent Proteins; Growth Cones; Hippocampus; Metalloendopeptidases; Neurons; Nystagmus, Optokinetic; Pseudopodia; Pyridinium Compounds; Quaternary Ammonium Compounds; Rats; Rats, Sprague-Dawley; Retina; Superior Colliculi; Synapses; Synaptophysin; Tetanus Toxin; Time Factors; Transcription Factors; Transfection; Visual Pathways; Zebrafish; Zebrafish Proteins}, Month = {Aug}, Number = {32}, Pages = {10939-51}, pmid = {20702722}, Pst = {ppublish}, Title = {Synaptic activity and activity-dependent competition regulates axon arbor maturation, growth arrest, and territory in the retinotectal projection}, Volume = {30}, Year = {2010}, url = {papers/BenFredj_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1556-10.2010}} @article{Dulla:2008, Abstract = {The neurotransmitter glutamate is the mediator of excitatory neurotransmission in the brain. Release of this signaling molecule is carefully controlled by multiple mechanisms, yet the methods available to measure released glutamate have been limited in spatial and/or temporal domains. We have developed a novel technique to visualize glutamate release in brain slices using three purified fluorescence (Forster) energy resonance transfer (FRET)-based glutamate sensor proteins. Using a simple loading protocol, the FRET sensor proteins diffuse deeply into the extracellular space and remain functional for many tens of minutes. This allows imaging of glutamate release in brain slices with simultaneous electrophysiological recordings and provides temporal and spatial resolution not previously possible. Using this glutamate FRET sensor loading and imaging protocol, we show that changes in network excitability and glutamate re-uptake alter evoked glutamate transients and produce correlated changes in evoked-cortical field potentials. Given the sophisticated advantages of brain slices for electrophysiological and imaging protocols, the ability to perform real-time imaging of glutamate in slices should lead to key insights in brain function relevant to plasticity, development and pathology. This technique also provides a unique assay of network activity that compliments alternative techniques such as voltage-sensitive dyes and multi-electrode arrays.}, Author = {Dulla, Chris and Tani, Hiroaki and Okumoto, Sakiko and Frommer, Wolf B and Reimer, Rich J and Huguenard, John R}, Date-Added = {2011-03-07 17:38:02 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {optical physiology;optical imaging;imaging;microscopy;Technique;Synapses;Synaptic Transmission;frontiers review}, Mesh = {Animals; Bacteria; Brain; Brain Chemistry; Calibration; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; GABA Agonists; Glutamic Acid; Indicators and Reagents; Male; Nerve Net; Pyridazines; Rats; Rats, Sprague-Dawley; Recombinant Proteins}, Month = {Mar}, Number = {2}, Pages = {306-19}, Pmc = {PMC2267481}, pmid = {18160134}, Pst = {ppublish}, Title = {Imaging of glutamate in brain slices using FRET sensors}, Volume = {168}, Year = {2008}, url = {papers/Dulla_JNeurosciMethods2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2007.10.017}} @article{Peterka:2011, Abstract = {In the last decades, imaging membrane potential has become a fruitful approach to study neural circuits, especially in invertebrate preparations with large, resilient neurons. At the same time, particularly in mammalian preparations, voltage imaging methods suffer from poor signal to noise and secondary side effects, and they fall short of providing single-cell resolution when imaging of the activity of neuronal populations. As an introduction to these techniques, we briefly review different voltage imaging methods (including organic fluorophores, SHG chromophores, genetic indicators, hybrid, nanoparticles, and intrinsic approaches) and illustrate some of their applications to neuronal biophysics and mammalian circuit analysis. We discuss their mechanisms of voltage sensitivity, from reorientation, electrochromic, or electro-optical phenomena to interaction among chromophores or membrane scattering, and highlight their advantages and shortcomings, commenting on the outlook for development of novel voltage imaging methods.}, Author = {Peterka, Darcy S and Takahashi, Hiroto and Yuste, Rafael}, Date-Added = {2011-03-07 17:36:00 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology;optical imaging;voltage sensor;Technique;review;frontiers review}, Mesh = {Animals; Diagnostic Imaging; Electrophysiology; Fluorescent Dyes; Membrane Potentials; Nanoparticles; Nerve Net; Neural Pathways; Neurons}, Month = {Jan}, Number = {1}, Pages = {9-21}, pmid = {21220095}, Pst = {ppublish}, Title = {Imaging voltage in neurons}, Volume = {69}, Year = {2011}, url = {papers/Peterka_Neuron2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.12.010}} @article{Sullivan:2005, Abstract = {In vivo two-photon calcium imaging provides the opportunity to monitor activity in multiple components of neural circuitry at once. Here we report the use of bulk-loading of fluorescent calcium indicators to record from axons, dendrites, and neuronal cell bodies in cerebellar cortex in vivo. In cerebellar folium crus IIa of anesthetized rats, we imaged the labeled molecular layer and identified all major cellular structures: Purkinje cells, interneurons, parallel fibers, and Bergmann glia. Using extracellular stimuli we evoked calcium transients corresponding to parallel fiber beam activity. This beam activity triggered prolonged calcium transients in interneurons, consistent with in vitro evidence for synaptic activation of N-methyl-d-aspartate receptors via glutamate spillover. We also observed spontaneous calcium transients in Purkinje cell dendrites that were identified as climbing-fiber-evoked calcium spikes by their size, time course, and sensitivity to AMPA receptor antagonist. Two-photon calcium imaging of bulk-loaded cerebellar cortex is thus well suited to optically monitor synaptic processing in the intact cerebellum.}, Author = {Sullivan, Megan R and Nimmerjahn, Axel and Sarkisov, Dmitry V and Helmchen, Fritjof and Wang, Samuel S-H}, Date-Added = {2011-03-07 17:33:45 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {optical physiology;optical imaging;frontiers review;calcium imaging;in vivo;Technique;microscopy;Multiphoton;Cerebellar Cortex}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Calcium; Cerebellar Cortex; Dendrites; Diagnostic Imaging; Dose-Response Relationship, Radiation; Egtazic Acid; Electric Stimulation; Evoked Potentials; Excitatory Amino Acid Antagonists; Nerve Net; Neurons; Poloxamer; Quinoxalines; Rats; Rats, Wistar; Valine}, Month = {Aug}, Number = {2}, Pages = {1636-44}, pmid = {16079125}, Pst = {ppublish}, Title = {In vivo calcium imaging of circuit activity in cerebellar cortex}, Volume = {94}, Year = {2005}, url = {papers/Sullivan_JNeurophysiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01013.2004}} @article{Kanold:2010, Abstract = {The developing mammalian cerebral cortex contains a distinct class of cells, subplate neurons (SPns), that play an important role during early development. SPns are the first neurons to be generated in the cerebral cortex, they reside in the cortical white matter, and they are the first to mature physiologically. SPns receive thalamic and neuromodulatory inputs and project into the developing cortical plate, mostly to layer 4. Thus SPns form one of the first functional cortical circuits and are required to relay early oscillatory activity into the developing cortical plate. Pathophysiological impairment or removal of SPns profoundly affects functional cortical development. SPn removal in visual cortex prevents the maturation of thalamocortical synapses, the maturation of inhibition in layer 4, the development of orientation selective responses and the formation of ocular dominance columns. SPn removal also alters ocular dominance plasticity during the critical period. Therefore, SPns are a key regulator of cortical development and plasticity. SPns are vulnerable to injury during prenatal stages and might provide a crucial link between brain injury in development and later cognitive malfunction.}, Author = {Kanold, Patrick O and Luhmann, Heiko J}, Date-Added = {2011-03-07 17:27:42 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {21 Activity-development;Neocortex;10 circuit formation;Spontaneous activity;Acetylcholine;review}, Mesh = {Animals; Cerebral Cortex; Humans; Neural Pathways; Neuronal Plasticity; Neurons; Stem Cells}, Pages = {23-48}, pmid = {20201645}, Pst = {ppublish}, Title = {The subplate and early cortical circuits}, Volume = {33}, Year = {2010}, url = {papers/Kanold_AnnuRevNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev-neuro-060909-153244}} @article{Knopfel:2010, Abstract = {This mini-symposium aims to provide an integrated perspective on recent developments in optogenetics. Research in this emerging field combines optical methods with targeted expression of genetically encoded, protein-based probes to achieve experimental manipulation and measurement of neural systems with superior temporal and spatial resolution. The essential components of the optogenetic toolbox consist of two kinds of molecular devices: actuators and reporters, which respectively enable light-mediated control or monitoring of molecular processes. The first generation of genetically encoded calcium reporters, fluorescent proteins, and neural activators has already had a great impact on neuroscience. Now, a second generation of voltage reporters, neural silencers, and functionally extended fluorescent proteins hold great promise for continuing this revolution. In this review, we will evaluate and highlight the limitations of presently available optogenic tools and discuss where these technologies and their applications are headed in the future.}, Author = {Kn{\"o}pfel, Thomas and Lin, Michael Z and Levskaya, Anselm and Tian, Lin and Lin, John Y and Boyden, Edward S}, Date-Added = {2011-03-07 17:21:29 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {optogenetics;optical physiology;frontiers review;Technique;review}, Mesh = {Fluorescent Dyes; Genetic Engineering; Neurosciences}, Month = {Nov}, Number = {45}, Pages = {14998-5004}, Pmc = {PMC2997431}, pmid = {21068304}, Pst = {ppublish}, Title = {Toward the second generation of optogenetic tools}, Volume = {30}, Year = {2010}, url = {papers/Knöpfel_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4190-10.2010}} @article{Toettcher:2011, Author = {Toettcher, Jared E and Voigt, Christopher A and Weiner, Orion D and Lim, Wendell A}, Date-Added = {2011-03-07 17:19:41 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optogenetics;optical physiology;frontiers review;Technique;review;}, Mesh = {Cell Biology; Cytological Techniques; Gene Expression Regulation; Genetic Techniques; Light; Luminescent Proteins; Photic Stimulation; Signal Transduction; Time Factors}, Month = {Jan}, Number = {1}, Pages = {35-8}, Pmc = {PMC3024327}, pmid = {21191370}, Pst = {ppublish}, Title = {The promise of optogenetics in cell biology: interrogating molecular circuits in space and time}, Volume = {8}, Year = {2011}, url = {papers/Toettcher_NatMethods2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.f.326}} @article{Ozden:2009, Abstract = {The inferior olive projects climbing fiber axons to cerebellar Purkinje neurons, where they trigger calcium-based dendritic spikes. These responses dynamically shape the immediate spike output of Purkinje cells as well as provide an instructive signal to guide long-term plasticity. Climbing fibers typically fire approximately once a second, and the instructive role is distributed over many such firing events. However, transmission of salient information on an immediate basis needs to occur on a shorter timescale during which a Purkinje cell would typically be activated by a climbing fiber only once. Here we show using in vivo calcium imaging in anesthetized mice and rats that sensory events are rapidly and reliably represented by momentary, simultaneous coactivation of microbands of adjacent Purkinje cells. Microbands were sagittally oriented and spanned up to 100 microm mediolaterally, representing hundreds of Purkinje cells distributed over multiple folia. Spontaneous and sensory-evoked microbands followed boundaries that were close or identical to one another and were desynchronized by olivary injection of the gap junction blocker mefloquine, indicating that excitation to the olive is converted to synchronized firing by electrical coupling. One-time activation of microbands could distinguish a sensory response from spontaneous activity with up to 98\% accuracy. Given the anatomy of the olivocerebellar system, microband synchrony may shape the output of neurons in the cerebellar nuclei either via powerful inhibition by Purkinje cells or by direct monosynaptic excitation from the inferior olive.}, Author = {Ozden, Ilker and Sullivan, Megan R and Lee, H Megan and Wang, Samuel S-H}, Date-Added = {2011-03-07 17:17:38 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {optical physiology;optical imaging;imaging;in vivo;Cerebellar Cortex;microscopy;Multiphoton}, Mesh = {Action Potentials; Animals; Animals, Newborn; Biophysics; Calcium; Cerebellum; Dendrites; Gap Junctions; Green Fluorescent Proteins; Likelihood Functions; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Nerve Fibers; Nerve Net; Olivary Nucleus; Physical Stimulation; Purkinje Cells; Rats; Rats, Wistar}, Month = {Aug}, Number = {34}, Pages = {10463-73}, Pmc = {PMC2783593}, pmid = {19710300}, Pst = {ppublish}, Title = {Reliable coding emerges from coactivation of climbing fibers in microbands of cerebellar Purkinje neurons}, Volume = {29}, Year = {2009}, url = {papers/Ozden_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0967-09.2009}} @article{Spitzer:2008, Abstract = {Electrical activity has numerous roles in early neuronal development. Calcium transients generated at low frequencies regulate neural induction and neuronal proliferation, migration and differentiation. Recent work demonstrates that these signals participate in specification of the transmitters expressed in different classes of neurons. Matching of postsynaptic receptor expression with the novel expression of transmitters ensues. These findings have intriguing implications for development, mature function and evolution of the nervous system.}, Author = {Spitzer, Nicholas C and Borodinsky, Laura N}, Date-Added = {2011-03-07 17:15:17 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Journal-Full = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {21 Activity-development;development;Spontaneous activity;Calcium;review;10 circuit formation;Synaptic Transmission}, Mesh = {Animals; Muscle, Striated; Nervous System; Neuromuscular Junction; Neurotransmitter Agents; Receptors, Neurotransmitter}, Month = {Apr}, Number = {1495}, Pages = {1393-9}, Pmc = {PMC2610128}, pmid = {18198155}, Pst = {ppublish}, Title = {Implications of activity-dependent neurotransmitter-receptor matching}, Volume = {363}, Year = {2008}, url = {papers/Spitzer_PhilosTransRSocLondBBiolSci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1098/rstb.2007.2257}} @article{Deisseroth:2011, Author = {Deisseroth, Karl}, Date-Added = {2011-03-07 17:12:40 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology;optogenetics;Technique;review;frontiers review}, Mesh = {Animals; Gene Expression Regulation; Genetic Techniques; Humans; Light; Neurons; Photic Stimulation}, Month = {Jan}, Number = {1}, Pages = {26-9}, pmid = {21191368}, Pst = {ppublish}, Title = {Optogenetics}, Volume = {8}, Year = {2011}, url = {papers/Deisseroth_NatMethods2011.pdf}, Bdsk-File-2 = {papers/Deisseroth_NatMethods2011a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.f.324}} @article{Arenkiel:2009, Abstract = {Brain function emerges from the morphologies, spatial organization and patterns of connectivity established between diverse sets of neurons. Historically, the notion that neuronal structure predicts function stemmed from classic histological staining and neuronal tracing methods. Recent advances in molecular genetics and imaging technologies have begun to reveal previously unattainable details about patterns of functional circuit connectivity and the subcellular organization of synapses in the living brain. This sophisticated molecular and genetic 'toolbox', coupled with new methods in optical and electron microscopy, provides an expanding array of techniques for probing neural anatomy and function.}, Author = {Arenkiel, Benjamin R and Ehlers, Michael D}, Date-Added = {2011-03-07 17:08:20 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology;frontiers review;Imaging;Technique;review;Genetic Engineering;optogenetics}, Mesh = {Animals; Brain; Molecular Biology; Neural Pathways; Neuroanatomy; Synapses}, Month = {Oct}, Number = {7266}, Pages = {900-7}, Pmc = {PMC2884271}, pmid = {19829369}, Pst = {ppublish}, Title = {Molecular genetics and imaging technologies for circuit-based neuroanatomy}, Volume = {461}, Year = {2009}, url = {papers/Arenkiel_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08536}} @article{Bozza:2004, Abstract = {Genetically encoded probes show great promise in permitting functional imaging of specified neuronal populations in the intact nervous system, yet their in vivo application has been limited. Here, we have targeted expression of synapto-pHluorin, a pH-sensitive protein that reports synaptic vesicle fusion, to olfactory sensory neurons in mouse. Synapto-pHluorin selectively labeled presynaptic terminals of sensory neurons in glomeruli of the olfactory bulb. Odorant stimulation evoked large-amplitude fluorescence increases that were localized to individual glomeruli in vivo, correlated with presynaptic calcium influx, graded with stimulus intensity, and stable over a period of days. Spatial patterns of odorant-activated glomeruli were distributed and did not change systematically with increasing carbon chain length, in contrast to the finely organized chemotopy that has been reported using other imaging methods. Targeted expression of synapto-pHluorin in mouse will permit the analysis of previously inaccessible neuronal populations and chronic imaging from genetically identified neurons in vivo.}, Author = {Bozza, Thomas and McGann, John P and Mombaerts, Peter and Wachowiak, Matt}, Date-Added = {2011-03-07 17:06:58 -0500}, Date-Modified = {2011-03-07 17:08:04 -0500}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology;optical imaging;calcium imaging;calcium sensor;imaging;microscopy;Multiphoton;Technique;frontiers review;Olfactory Bulb}, Mesh = {Aldehydes; Animals; Brain Mapping; Cloning, Molecular; Dextrans; Diagnostic Imaging; Dose-Response Relationship, Drug; Evoked Potentials; Gene Expression; Gene Targeting; Green Fluorescent Proteins; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Neurons, Afferent; Odors; Olfactory Bulb; Olfactory Marker Protein; Olfactory Mucosa; Protein Transport; Stimulation, Chemical; Time Factors}, Month = {Apr}, Number = {1}, Pages = {9-21}, pmid = {15066261}, Pst = {ppublish}, Title = {In vivo imaging of neuronal activity by targeted expression of a genetically encoded probe in the mouse}, Volume = {42}, Year = {2004}, url = {papers/Bozza_Neuron2004.pdf}} @article{Havekes:2009, Abstract = {One of the major challenges in the field of neurobiology is to elucidate the molecular machinery that underlies the formation and storage of memories. For many decades, genetic studies in the fruit fly (Drosophila melanogaster) have provided insight into the role of specific genes underlying memory storage. Although these pioneering studies were groundbreaking, a transition to a mammalian system more closely resembling the human brain is critical for the translation of basic research findings into therapeutic strategies in humans. Because the mouse (Mus musculus) shares the complex genomic and neuroanatomical organization of mammals and there is a wealth of molecular tools that are available to manipulate gene function in mice, the mouse has become the primary model for research into the genetic basis of mammalian memory. Another major advantage of mouse research is the ability to examine in vivo electrophysiological processes, such as synaptic plasticity and neuronal firing patterns during behavior (e.g., the analysis of place cell activity). The focus on mouse models for memory research has led to the development of sophisticated behavioral protocols capable of exploring the role of particular genes in distinct phases of learning and memory formation, which is one of the major accomplishments of the past decade. In this chapter, we will give an overview of several state of the art genetic approaches to study gene function in the mouse brain in a spatially and temporally restricted fashion.}, Author = {Havekes, Robbert and Abel, Ted}, Date-Added = {2011-03-07 17:02:19 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Adv Genet}, Journal-Full = {Advances in genetics}, Keywords = {frontiers review;optical physiology;Technique;Genetic Engineering;Mouse;Circuits;connectivity;Synaptic Transmission}, Mesh = {Animals; Behavior; Brain; Gene Targeting; Genes, Dominant; Genetic Research; Mice; Models, Animal; Nerve Net; Pharmacogenetics}, Pages = {1-38}, Pmc = {PMC2861997}, pmid = {19615530}, Pst = {ppublish}, Title = {Genetic dissection of neural circuits and behavior in Mus musculus}, Volume = {65}, Year = {2009}, url = {papers/Havekes_AdvGenet2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0065-2660(09)65001-X}} @article{Bleckert:2011, Abstract = {In the adult nervous system, chemical neurotransmission between neurons is essential for information processing. However, neurotransmission is also important for patterning circuits during development, but its precise roles have yet to be identified, and some remain highly debated. Here, we highlight viewpoints that have come to be widely accepted or still challenged. We discuss how distinct techniques and model systems employed to probe the developmental role of neurotransmission may reconcile disparate ideas. We underscore how the effects of perturbing neurotransmission during development vary with model systems, the stage of development when transmission is altered, the nature of the perturbation, and how connectivity is assessed. Based on findings in circuits with connectivity arranged in layers, we raise the possibility that there exist constraints in neuronal network design that limit the role of neurotransmission. We propose that activity-dependent mechanisms are effective in refining connectivity patterns only when inputs from different cells are close enough, spatially, to influence each other's outcome.}, Author = {Bleckert, Adam and Wong, Rachel O L}, Date-Added = {2011-03-07 17:02:19 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Bioessays}, Journal-Full = {BioEssays : news and reviews in molecular, cellular and developmental biology}, Keywords = {21 Activity-development;development;frontiers review;optical physiology;Technique;Genetic Engineering;Mouse;Circuits;connectivity;Synaptic Transmission;Sensory Deprivation;visual system;retina;Spontaneous activity;retinal wave paper}, Month = {Jan}, Number = {1}, Pages = {61-72}, pmid = {21110347}, Pst = {ppublish}, Title = {Identifying roles for neurotransmission in circuit assembly: insights gained from multiple model systems and experimental approaches}, Volume = {33}, Year = {2011}, url = {papers/Bleckert_Bioessays2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/bies.201000095}} @article{Nevin:2010, Abstract = {The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.}, Author = {Nevin, Linda M and Robles, Estuardo and Baier, Herwig and Scott, Ethan K}, Date-Added = {2011-03-07 17:00:19 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {BMC Biol}, Journal-Full = {BMC biology}, Keywords = {frontiers review;optic tectum;function;Superior Colliculus;connectivity;Genetic Engineering;circuitry;visual system;multisensory integration;retina}, Mesh = {Animals; Models, Neurological; Nerve Net; Neurons; Superior Colliculi; Visual Pathways; Visual Perception; Zebrafish}, Pages = {126}, Pmc = {PMC2949621}, pmid = {20920150}, Pst = {epublish}, Title = {Focusing on optic tectum circuitry through the lens of genetics}, Volume = {8}, Year = {2010}, url = {papers/Nevin_BMCBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1741-7007-8-126}} @article{Spitzer:2006, Abstract = {The construction of the brain during embryonic development was thought to be largely independent of its electrical activity. In this view, proliferation, migration and differentiation of neurons are driven entirely by genetic programs and activity is important only at later stages in refinement of connections. However, recent findings demonstrate that activity plays essential roles in early development of the nervous system. Activity has similar roles in the incorporation of newly born neurons in the adult nervous system, suggesting that there are general rules underlying activity-dependent development. The extensive involvement of activity makes it likely that it is required at all developmental stages as a necessary partner with genetic programs.}, Author = {Spitzer, Nicholas C}, Date-Added = {2011-03-07 16:50:28 -0500}, Date-Modified = {2012-11-15 22:10:32 +0000}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Activity-development;Spontaneous activity;development;10 circuit formation;frontiers review;Synapses;Electric Conductivity;Cell Differentiation;21 Neurophysiology;Animals;Brain;Neurons;review; Gene Expression; Transcription Factors; Activity-development; Structure-Activity Relationship; axon guidance; cell migration}, Mesh = {Animals; Brain; Cell Differentiation; Electric Conductivity; Neurons; Synapses}, Month = {Dec}, Number = {7120}, Pages = {707-12}, pmid = {17151658}, Pst = {ppublish}, Title = {Electrical activity in early neuronal development}, Volume = {444}, Year = {2006}, url = {papers/Spitzer_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05300}} @article{Nichols:2009, Abstract = {Understanding how discreet tissues and neuronal circuits function in relation to the whole organism to regulate physiological processes and behaviors is a fundamental goal of modern biological science. Powerful and important new tools in this discovery process are modified G-protein coupled receptors (GPCRs) known as 'Receptors Activated Solely by Synthetic Ligands (RASSLs),' and 'Designer Receptors Exclusively Activated by a Designer Drug (DREADDs).' Collectively, these are GPCRs modified either through rational design (RASSLs) or directed molecular evolution (DREADDs), that do not respond to native ligand, but functionally respond only to synthetic ligands. Importantly, the utility of these receptors is not limited to examination of the role of GPCR-coupled effector signal transduction pathways. Due to the near ubiquitous expression of GPCRs throughout an organism, this technology, combined with whole animal transgenics to selectively target expression, has the ability to regulate activity of discreet tissues and neuronal circuits through effector pathway modulation to study function and behavior throughout the organism. Advantages over other systems currently used to modify in vivo function include the ability to rapidly, selectively and reversibly manipulate defined signal transduction pathways both in short term and long term studies, and no need for specialized equipment due to convenient systemic treatment with activating ligand.}, Author = {Nichols, Charles D and Roth, Bryan L}, Date-Added = {2011-03-07 16:50:28 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review;activity manipulation;Synaptic Transmission;Genetic Engineering}, Pages = {16}, Pmc = {PMC2773177}, pmid = {19893765}, Pst = {ppublish}, Title = {Engineered G-protein Coupled Receptors are Powerful Tools to Investigate Biological Processes and Behaviors}, Volume = {2}, Year = {2009}, url = {papers/Nichols_FrontMolNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.016.2009}} @article{Granstedt:2009, Abstract = {The study of coordinated activity in neuronal circuits has been challenging without a method to simultaneously report activity and connectivity. Here we present the first use of pseudorabies virus (PRV), which spreads through synaptically connected neurons, to express a fluorescent calcium indicator protein and monitor neuronal activity in a living animal. Fluorescence signals were proportional to action potential number and could reliably detect single action potentials in vitro. With two-photon imaging in vivo, we observed both spontaneous and stimulated activity in neurons of infected murine peripheral autonomic submandibular ganglia (SMG). We optically recorded the SMG response in the salivary circuit to direct electrical stimulation of the presynaptic axons and to physiologically relevant sensory stimulation of the oral cavity. During a time window of 48 hours after inoculation, few spontaneous transients occurred. By 72 hours, we identified more frequent and prolonged spontaneous calcium transients, suggestive of neuronal or tissue responses to infection that influence calcium signaling. Our work establishes in vivo investigation of physiological neuronal circuit activity and subsequent effects of infection with single cell resolution.}, Author = {Granstedt, Andrea E and Szpara, Moriah L and Kuhn, Bernd and Wang, Samuel S-H and Enquist, Lynn W}, Date-Added = {2011-03-07 16:50:28 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {optical physiology;optical imaging;frontiers review;Viral;viral gene transfer;calcium sensor}, Mesh = {Action Potentials; Animals; Calcium; Calcium Signaling; Electrons; Fluorescent Dyes; Ganglia; Herpesvirus 1, Suid; Mice; Microscopy, Fluorescence; Models, Neurological; Neurons; Probability; Saliva; Time Factors}, Number = {9}, Pages = {e6923}, Pmc = {PMC2735035}, pmid = {19742327}, Pst = {epublish}, Title = {Fluorescence-based monitoring of in vivo neural activity using a circuit-tracing pseudorabies virus}, Volume = {4}, Year = {2009}, url = {papers/Granstedt_PLoSOne2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0006923}} @article{Peron:2011, Author = {Peron, Simon and Svoboda, Karel}, Date-Added = {2011-03-07 16:50:28 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optogenetics;optical physiology;frontiers review;Technique}, Mesh = {Animals; Gene Expression Regulation; Genetic Techniques; Light; Neurons; Organ Specificity; Photic Stimulation}, Month = {Jan}, Number = {1}, Pages = {30-4}, pmid = {21191369}, Pst = {ppublish}, Title = {From cudgel to scalpel: toward precise neural control with optogenetics}, Volume = {8}, Year = {2011}, url = {papers/Peron_NatMethods2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.f.325}} @article{Adamantidis:2010, Abstract = {How does the brain regulate the sleep-wake cycle? What are the temporal codes of sleep and wake-promoting neural circuits? How do these circuits interact with each other across the light/dark cycle? Over the past few decades, many studies from a variety of disciplines have made substantial progress in answering these fundamental questions. For example, neurobiologists have identified multiple, redundant wake-promoting circuits in the brainstem, hypothalamus, and basal forebrain. Sleep-promoting circuits have been found in the preoptic area and hypothalamus. One of the greatest challenges in recent years has been to selectively record and manipulate these sleep-wake centers in vivo with high spatial and temporal resolution. Recent developments in microbial opsin-based neuromodulation tools, collectively referred to as "optogenetics," have provided a novel method to demonstrate causal links between neural activity and specific behaviors. Here, we propose to use optogenetics as a fundamental tool to probe the necessity, sufficiency, and connectivity of defined neural circuits in the regulation of sleep and wakefulness.}, Author = {Adamantidis, Antoine and Carter, Matthew C and de Lecea, Luis}, Date-Added = {2011-03-07 16:45:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review; example;optical physiology; technique}, Pages = {31}, Pmc = {PMC2814554}, pmid = {20126433}, Pst = {epublish}, Title = {Optogenetic deconstruction of sleep-wake circuitry in the brain}, Volume = {2}, Year = {2010}, url = {papers/Adamantidis_FrontMolNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.031.2009}} @article{Bregestovski:2009, Abstract = {This review briefly discusses the main approaches for monitoring chloride (Cl(-)), the most abundant physiological anion. Noninvasive monitoring of intracellular Cl(-) ([Cl(-)]i) is a challenging task owing to two main difficulties: (i) the low transmembrane ratio for Cl(-), approximately 10:1; and (ii) the small driving force for Cl(-), as the Cl(-) reversal potential (E(Cl)) is usually close to the resting potential of the cells. Thus, for reliable monitoring of intracellular Cl(-), one has to use highly sensitive probes. From several methods for intracellular Cl(-) analysis, genetically encoded chloride indicators represent the most promising tools. Recent achievements in the development of genetically encoded chloride probes are based on the fact that yellow fluorescent protein (YFP) exhibits Cl(-)-sensitivity. YFP-based probes have been successfully used for quantitative analysis of Cl(-) transport in different cells and for high-throughput screening of modulators of Cl(-)-selective channels. Development of a ratiometric genetically encoded probe, Clomeleon, has provided a tool for noninvasive estimation of intracellular Cl(-) concentrations. While the sensitivity of this protein to Cl(-) is low (EC(50) about 160 mM), it has been successfully used for monitoring intracellular Cl(-) in different cell types. Recently a CFP-YFP-based probe with a relatively high sensitivity to Cl(-) (EC(50) about 30 mM) has been developed. This construct, termed Cl-Sensor, allows ratiometric monitoring using the fluorescence excitation ratio. Of particular interest are genetically encoded probes for monitoring of ion channel distribution and activity. A new molecular probe has been constructed by introducing into the cytoplasmic domain of the Cl(-)-selective glycine receptor (GlyR) channel the CFP-YFP-based Cl-Sensor. This construct, termed BioSensor-GlyR, has been successfully expressed in cell lines. The new genetically encoded chloride probes offer means of screening pharmacological agents, analysis of Cl(-) homeostasis and functions of Cl(-)-selective channels under different physiological and pathological conditions.}, Author = {Bregestovski, Piotr and Waseem, Tatyana and Mukhtarov, Marat}, Date-Added = {2011-03-07 16:45:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review; example; optical physiology; technique}, Pages = {15}, Pmc = {PMC2802328}, pmid = {20057911}, Pst = {ppublish}, Title = {Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity}, Volume = {2}, Year = {2009}, url = {papers/Bregestovski_FrontMolNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.015.2009}} @article{Hodge:2009, Abstract = {Ion channels are the determinants of excitability; therefore, manipulation of their levels and properties provides an opportunity for the investigator to modulate neuronal and circuit function. There are a number of ways to suppress electrical activity in Drosophila neurons, for instance, over-expression of potassium channels (i.e. Shaker Kv1, Shaw Kv3, Kir2.1 and DORK) that are open at resting membrane potential. This will result in increased potassium efflux and membrane hyperpolarisation setting resting membrane potential below the threshold required to fire action potentials. Alternatively over-expression of other channels, pumps or co-transporters that result in a hyperpolarised membrane potential will also prevent firing. Lastly, neurons can be inactivated by, disrupting or reducing the level of functional voltage-gated sodium (Nav1 paralytic) or calcium (Cav2 cacophony) channels that mediate the depolarisation phase of action potentials. Similarly, strategies involving the opposite channel manipulation should allow net depolarisation and hyperexcitation in a given neuron. These changes in ion channel expression can be brought about by the versatile transgenic (i.e. Gal4/UAS based) systems available in Drosophila allowing fine temporal and spatial control of (channel) transgene expression. These systems are making it possible to electrically inactivate (or hyperexcite) any neuron or neural circuit in the fly brain, and much like an exquisite lesion experiment, potentially elucidate whatever interesting behaviour or phenotype each network mediates. These techniques are now being used in Drosophila to reprogram electrical activity of well-defined circuits and bring about robust and easily quantifiable changes in behaviour, allowing different models and hypotheses to be rapidly tested.}, Author = {Hodge, James J L}, Date-Added = {2011-03-07 16:45:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review; example; optical physiology; technique}, Pages = {13}, Pmc = {PMC2741205}, pmid = {19750193}, Pst = {ppublish}, Title = {Ion channels to inactivate neurons in Drosophila}, Volume = {2}, Year = {2009}, url = {papers/Hodge_FrontMolNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.013.2009}} @article{Holford:2009, Abstract = {Neuronal circuits depend on the precise regulation of cell-surface receptors and ion channels. An ongoing challenge in neuroscience research is deciphering the functional contribution of specific receptors and ion channels using engineered modulators. A novel strategy, termed "tethered toxins", was recently developed to characterize neuronal circuits using the evolutionary derived selectivity of venom peptide toxins and endogenous peptide ligands, such as lynx1 prototoxins. Herein, the discovery and engineering of cell-surface tethered peptides is reviewed, with particular attention given to their cell-autonomy, modular composition, and genetic targeting in different model organisms. The relative ease with which tethered peptides can be engineered, coupled with the increasing number of neuroactive venom toxins and ligand peptides being discovered, imply a multitude of potentially innovative applications for manipulating neuronal circuits and tissue-specific cell networks, including treatment of disorders caused by malfunction of receptors and ion channels.}, Author = {Holford, Mand{\"e} and Auer, Sebastian and Laqua, Martin and Iba{\~n}ez-Tallon, Ines}, Date-Added = {2011-03-07 16:45:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review; example; optical physiology; technique}, Pages = {21}, Pmc = {PMC2776481}, pmid = {19915728}, Pst = {ppublish}, Title = {Manipulating neuronal circuits with endogenous and recombinant cell-surface tethered modulators}, Volume = {2}, Year = {2009}, url = {papers/Holford_FrontMolNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.021.2009}} @article{Perron:2009a, Abstract = {Over the last decade, optical neuroimaging methods have been enriched by engineered biosensors derived from fluorescent protein (FP) reporters fused to protein detectors that convert physiological signals into changes of intrinsic FP fluorescence. These FP-based indicators are genetically encoded, and hence targetable to specific cell populations within networks of heterologous cell types. Among this class of biosensors, the development of optical probes for membrane potential is both highly desirable and challenging. A suitable FP voltage sensor would indeed be a valuable tool for monitoring the activity of thousands of individual neurons simultaneously in a non-invasive manner. Previous prototypic genetically-encoded FP voltage indicators achieved a proof of principle but also highlighted several difficulties such as poor cell surface targeting and slow kinetics. Recently, we developed a new series of FRET-based Voltage-Sensitive Fluorescent Proteins (VSFPs), referred to as VSFP2s, with efficient targeting to the plasma membrane and high responsiveness to membrane potential signaling in excitable cells. In addition to these FRET-based voltage sensors, we also generated a third series of probes consisting of single FPs with response kinetics suitable for the optical imaging of fast neuronal signals. These newly available genetically-encoded reporters for membrane potential will be instrumental for future experimental approaches directed toward the understanding of neuronal network dynamics and information processing in the brain. Here, we review the development and current status of these novel fluorescent probes.}, Author = {Perron, Amelie and Mutoh, Hiroki and Akemann, Walther and Gautam, Sunita Ghimire and Dimitrov, Dimitar and Iwamoto, Yuka and Kn{\"o}pfel, Thomas}, Date-Added = {2011-03-07 16:45:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review; example; optical physiology;voltage sensor; technique}, Pages = {5}, Pmc = {PMC2706653}, pmid = {19623246}, Pst = {ppublish}, Title = {Second and third generation voltage-sensitive fluorescent proteins for monitoring membrane potential}, Volume = {2}, Year = {2009}, url = {papers/Perron_FrontMolNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.005.2009}} @article{Reijmers:2009, Abstract = {The use of molecular tools to study the neurobiology of complex behaviors has been hampered by an inability to target the desired changes to relevant groups of neurons. Specific memories and specific sensory representations are sparsely encoded by a small fraction of neurons embedded in a sea of morphologically and functionally similar cells. In this review we discuss genetics techniques that are being developed to address this difficulty. In several studies the use of promoter elements that are responsive to neural activity have been used to drive long-lasting genetic alterations into neural ensembles that are activated by natural environmental stimuli. This approach has been used to examine neural activity patterns during learning and retrieval of a memory, to examine the regulation of receptor trafficking following learning and to functionally manipulate a specific memory trace. We suggest that these techniques will provide a general approach to experimentally investigate the link between patterns of environmentally activated neural firing and cognitive processes such as perception and memory.}, Author = {Reijmers, Leon and Mayford, Mark}, Date-Added = {2011-03-07 16:45:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review; example; optical physiology; technique}, Pages = {27}, Pmc = {PMC2802553}, pmid = {20057936}, Pst = {ppublish}, Title = {Genetic control of active neural circuits}, Volume = {2}, Year = {2009}, url = {papers/Reijmers_FrontMolNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.027.2009}} @article{Tessier:2009, Abstract = {In many nervous systems, the establishment of neural circuits is known to proceed via a two-stage process; (1) early, activity-independent wiring to produce a rough map characterized by excessive synaptic connections, and (2) subsequent, use-dependent pruning to eliminate inappropriate connections and reinforce maintained synapses. In invertebrates, however, evidence of the activity-dependent phase of synaptic refinement has been elusive, and the dogma has long been that invertebrate circuits are "hard-wired" in a purely activity-independent manner. This conclusion has been challenged recently through the use of new transgenic tools employed in the powerful Drosophila system, which have allowed unprecedented temporal control and single neuron imaging resolution. These recent studies reveal that activity-dependent mechanisms are indeed required to refine circuit maps in Drosophila during precise, restricted windows of late-phase development. Such mechanisms of circuit refinement may be key to understanding a number of human neurological diseases, including developmental disorders such as Fragile X syndrome (FXS) and autism, which are hypothesized to result from defects in synaptic connectivity and activity-dependent circuit function. This review focuses on our current understanding of activity-dependent synaptic connectivity in Drosophila, primarily through analyzing the role of the fragile X mental retardation protein (FMRP) in the Drosophila FXS disease model. The particular emphasis of this review is on the expanding array of new genetically-encoded tools that are allowing cellular events and molecular players to be dissected with ever greater precision and detail.}, Author = {Tessier, Charles R and Broadie, Kendal}, Date-Added = {2011-03-07 16:45:36 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Front Mol Neurosci}, Journal-Full = {Frontiers in molecular neuroscience}, Keywords = {frontiers review; example; optical physiology; technique}, Pages = {8}, Pmc = {PMC2724028}, pmid = {19668708}, Pst = {ppublish}, Title = {Activity-dependent modulation of neural circuit synaptic connectivity}, Volume = {2}, Year = {2009}, url = {papers/Tessier_FrontMolNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.02.008.2009}} @article{Gaietta:2002, Abstract = {Recombinant proteins containing tetracysteine tags can be successively labeled in living cells with different colors of biarsenical fluorophores so that older and younger protein molecules can be sharply distinguished by both fluorescence and electron microscopy. Here we used this approach to show that newly synthesized connexin43 was transported predominantly in 100- to 150-nanometer vesicles to the plasma membrane and incorporated at the periphery of existing gap junctions, whereas older connexins were removed from the center of the plaques into pleiomorphic vesicles of widely varying sizes. Selective imaging by correlated optical and electron microscopy of protein molecules of known ages will clarify fundamental processes of protein trafficking in situ.}, Author = {Gaietta, Guido and Deerinck, Thomas J and Adams, Stephen R and Bouwer, James and Tour, Oded and Laird, Dale W and Sosinsky, Gina E and Tsien, Roger Y and Ellisman, Mark H}, Date-Added = {2011-03-07 16:41:49 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Cell Adhesion;cell interaction;imaging;Technique;Gap Junctions}, Mesh = {3,3'-Diaminobenzidine; Amino Acid Motifs; Animals; Arsenicals; Cell Line; Cell Membrane; Connexin 43; Cysteine; Endocytosis; Exocytosis; Fluoresceins; Fluorescence; Fluorescent Dyes; Gap Junctions; Hela Cells; Humans; Microscopy, Confocal; Microscopy, Electron; Microscopy, Immunoelectron; Organometallic Compounds; Oxazines; Patch-Clamp Techniques; Protein Transport; Recombinant Proteins; Transport Vesicles}, Month = {Apr}, Number = {5567}, Pages = {503-7}, pmid = {11964472}, Pst = {ppublish}, Title = {Multicolor and electron microscopic imaging of connexin trafficking}, Volume = {296}, Year = {2002}, url = {papers/Gaietta_Science2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1068793}} @article{Okaty:2011, Abstract = {Expression profiling of restricted neural populations using microarrays can facilitate neuronal classification and provide insight into the molecular bases of cellular phenotypes. Due to the formidable heterogeneity of intermixed cell types that make up the brain, isolating cell types prior to microarray processing poses steep technical challenges that have been met in various ways. These methodological differences have the potential to distort cell-type-specific gene expression profiles insofar as they may insufficiently filter out contaminating mRNAs or induce aberrant cellular responses not normally present in vivo. Thus we have compared the repeatability, susceptibility to contamination from off-target cell-types, and evidence for stress-responsive gene expression of five different purification methods - Laser Capture Microdissection (LCM), Translating Ribosome Affinity Purification (TRAP), Immunopanning (PAN), Fluorescence Activated Cell Sorting (FACS), and manual sorting of fluorescently labeled cells (Manual). We found that all methods obtained comparably high levels of repeatability, however, data from LCM and TRAP showed significantly higher levels of contamination than the other methods. While PAN samples showed higher activation of apoptosis-related, stress-related and immediate early genes, samples from FACS and Manual studies, which also require dissociated cells, did not. Given that TRAP targets actively translated mRNAs, whereas other methods target all transcribed mRNAs, observed differences may also reflect translational regulation.}, Author = {Okaty, Benjamin W and Sugino, Ken and Nelson, Sacha B}, Date-Added = {2011-03-07 16:40:46 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {genetics;genes;Neocortex;development;Technique;mouse;}, Number = {1}, Pages = {e16493}, Pmc = {PMC3029380}, pmid = {21304595}, Pst = {epublish}, Title = {A quantitative comparison of cell-type-specific microarray gene expression profiling methods in the mouse brain}, Volume = {6}, Year = {2011}, url = {papers/Okaty_PLoSOne2011.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0016493}} @article{Kleinfeld:1994, Abstract = {1. The procerebral (PC) lobe of the terrestrial mollusk Limax maximus contains a highly interconnected network of local olfactory interneurons that receives ipsilateral axonal projections from superior and inferior noses. This network exhibits an approximately 0.7-Hz intrinsic oscillation in its local field potential (LFP). 2. Intracellular recordings show that the lobe contains at least two classes of neurons with activity phase locked to the oscillation. Neurons in one class produce periodic bursts of spikes, followed by a period of hyperpolarization and subsequently a depolarizing afterpotential. There is a small but significant chance for a second burst to occur during the depolarizing afterpotential; this leads to a double event in the LFP. Bursting neurons constitute approximately 10\% of the neurons in the lobe. 3. Neurons in the other class fire infrequently and do not produce periodic bursts of action potentials. However, they receive strong, periodic inhibitory input during every event in the LFP. These nonbursting cells constitute the major fraction of neurons in the lobe. There is a clear correlation between the periodic burst of action potentials in the bursting neurons and the hyperpolarization seen in nonbursting neurons. 4. Optical techniques are used to image the spatially averaged transmembrane potentials in preparations stained with voltage-sensitive dyes. The results of simultaneous optical and electrical measurements show that the major part of the optical signal can be interpreted as a superposition of the intracellular signals arising from the bursting and nonbursting neurons. 5. Successive images of the entire PC lobe show waves of electrical activity that span the width of the lobe and travel its full length along a longitudinal axis. The direction of propagation in the unperturbed lobe is always from the distal to the proximal end. The wavelength varies between preparations but is on the order of the length of the preparation. 6. One-dimensional images along the longitudinal axis of the lobe are used to construct a space-time map of the optical activity, from which we calculate the absolute contribution of bursting and nonbursting neurons to the optical signal. The contribution of the intracellular signals from the two cell types appears to vary systematically across the lobe; bursting cells dominate at middle and proximal locations, and nonbursting cells dominate at distal locations. 7. The direction and form of the waves can be perturbed either by microsurgical manipulation of the preparation or by chemical modulation of its synaptic and neuronal properties.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Kleinfeld, D and Delaney, K R and Fee, M S and Flores, J A and Tank, D W and Gelperin, A}, Date-Added = {2011-03-07 16:38:23 -0500}, Date-Modified = {2011-03-07 16:39:21 -0500}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Spontaneous activity;optical imaging;optical physiology;Computational Biology;21 Neurophysiology}, Mesh = {Animals; Culture Techniques; Ganglia, Invertebrate; Interneurons; Membrane Potentials; Nerve Net; Olfactory Bulb; Olfactory Nerve; Olfactory Pathways; Orientation; Smell; Snails; Synaptic Transmission}, Month = {Sep}, Number = {3}, Pages = {1402-19}, pmid = {7807221}, Pst = {ppublish}, Title = {Dynamics of propagating waves in the olfactory network of a terrestrial mollusk: an electrical and optical study}, Volume = {72}, Year = {1994}, url = {papers/Kleinfeld_JNeurophysiol1994.pdf}} @article{Meister:1994, Abstract = {Throughout the central nervous system, information about the outside world is represented collectively by large groups of cells, often arranged in a series of 2-dimensional maps connected by tracts with many fibers. To understand how such a circuit encodes and processes information, one must simultaneously observe the signals carried by many of its cells. This article describes a new method for monitoring the simultaneous electrical activity of many neurons in a functioning piece of retina. Extracellular action potentials are recorded with a planar array of 61 microelectrodes, which provides a natural match to the flat mosaic of retinal ganglion cells. The voltage signals are processed in real time to extract the spike trains from up to 100 neurons. We also present a method of visual stimulation and data analysis that allows a rapid characterization of each neuron's visual response properties. A randomly flickering display is used to elicit spike trains from the ganglion cell population. Analysis of the correlations between each spike train and the flicker stimulus results in a simple description of each ganglion cell's functional properties. The combination of these tools will allow detailed study of how the population of optic nerve fibers encodes a visual scene.}, Author = {Meister, M and Pine, J and Baylor, D A}, Date-Added = {2011-03-07 16:35:28 -0500}, Date-Modified = {2011-03-07 16:36:29 -0500}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {Spontaneous activity;development;retina;multielectrode;methods;Technique;Software;Computational Biology}, Mesh = {Action Potentials; Animals; Automatic Data Processing; Electrophysiology; Neurons; Photic Stimulation; Retina; Software; Vertebrates; Visual Fields}, Month = {Jan}, Number = {1}, Pages = {95-106}, pmid = {8189755}, Pst = {ppublish}, Title = {Multi-neuronal signals from the retina: acquisition and analysis}, Volume = {51}, Year = {1994}, url = {papers/Meister_JNeurosciMethods1994.pdf}} @article{Wachowiak:2004, Abstract = {Glomeruli in the olfactory bulb are anatomically discrete modules receiving input from idiotypic olfactory sensory neurons. To examine the functional organization of sensory inputs to individual glomeruli, we loaded olfactory sensory neurons with a Ca(2+) indicator and measured odorant-evoked presynaptic Ca(2+) signals within single glomeruli by using two-photon microscopy in anaesthetized mice. Odorants evoked patterns of discrete Ca(2+) signals throughout the neuropil of a glomerulus. Across glomeruli, Ca(2+) signals occurred with equal probability in all glomerular regions. Within single glomeruli, the pattern of intraglomerular Ca(2+) signals was indistinguishable for stimuli of different duration, identity, and concentration. Moreover, the response time course of the signals was similar throughout the glomerulus. Hence, sensory inputs to individual glomeruli are spatially heterogeneous but seem to be functionally indiscriminate. These results support the view of olfactory glomeruli as functional units in representing sensory information.}, Author = {Wachowiak, Matt and Denk, Winfried and Friedrich, Rainer W}, Date-Added = {2011-03-07 16:33:34 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;imaging;in vivo;Olfactory Bulb;Multiphoton;microscopy;function}, Mesh = {Animals; Calcium; Calcium Signaling; Image Processing, Computer-Assisted; Mice; Microscopy, Fluorescence; Olfactory Bulb; Olfactory Receptor Neurons; Photons; Smell; Stimulation, Chemical; Synapses}, Month = {Jun}, Number = {24}, Pages = {9097-102}, Pmc = {PMC428479}, pmid = {15184670}, Pst = {ppublish}, Title = {Functional organization of sensory input to the olfactory bulb glomerulus analyzed by two-photon calcium imaging}, Volume = {101}, Year = {2004}, url = {papers/Wachowiak_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0400438101}} @article{Yhip:1990, Abstract = {The topographic order of the retinocollicular projection in the rat was examined from birth until maturity. Small, localized deposits of rhodamine-filled latex microspheres were placed into the superior colliculus at different locations. To minimize labeling fibers of passage deposit sites were typically, although not exclusively, placed into the caudal-lateral pole of the colliculus. Examination of the area and density of labeled cells in the retinae of these animals led to the following conclusions: (1) At each age examined, the location of the majority of labeled cells was observed to be in appropriate topographic register with the deposit site in the superior colliculus. (2) Confirming the work of previous investigators, errors in topographic projection were observed. These were present in both the contralateral and ipsilateral retinae and decreased with increasing postnatal age. The mature pattern was present by P10. (3) Quantitatively, the number of retinal ganglion cells terminating nontopographically within the colliculus constituted a relatively minor proportion of the total number of labeled cells in both retinae. It is concluded that the majority of the retinal ganglion cells make topographically appropriate terminations within the superior colliculus during development.}, Author = {Yhip, J P and Kirby, M A}, Date-Added = {2011-03-07 16:30:55 -0500}, Date-Modified = {2011-03-07 16:32:52 -0500}, Journal = {Vis Neurosci}, Journal-Full = {Visual neuroscience}, Keywords = {21 Activity-development;development;Superior Colliculus;optic tectum;retina;visual system;retinal wave paper}, Mesh = {Animals; Cell Count; Drug Carriers; Microspheres; Neural Pathways; Rats; Rats, Inbred Strains; Retina; Retinal Ganglion Cells; Rhodamines; Superior Colliculi; Visual Pathways}, Month = {Apr}, Number = {4}, Pages = {313-29}, pmid = {2271447}, Pst = {ppublish}, Title = {Topographic organization of the retinocollicular projection in the neonatal rat}, Volume = {4}, Year = {1990}, url = {papers/Yhip_VisNeurosci1990.PDF}} @article{Chen:2000c, Abstract = {Anatomical rearrangement of retinogeniculate connections contributes to the refinement of synaptic circuits in the developing visual system, but the underlying changes in synaptic function are unclear. Here, we study such changes in mouse brain slices. Each geniculate cell receives a surprisingly large number of retinal inputs (>20) well after eye-specific zones are formed. All but one to three of these inputs are eliminated over a 3-week period spanning eye opening. Remaining inputs are strengthened approximately 50-fold, in part through an increase in quantal size, but primarily through an increase in the number of release sites. Changes in release probability do not contribute significantly. Thus, a redistribution of release sites from many inputs to few inputs at this late developmental stage contributes to the precise receptive fields of thalamic relay neurons.}, Author = {Chen, C and Regehr, W G}, Date-Added = {2011-03-07 16:26:26 -0500}, Date-Modified = {2011-03-07 16:29:35 -0500}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;retina;LGN;structural remodeling;plasticity;development;axon guidance;axons;Patch-Clamp Techniques/methods;mouse;Synapses;Synaptic Transmission}, Mesh = {Aging; Animals; Excitatory Postsynaptic Potentials; Geniculate Bodies; Mice; Nerve Fibers; Retina; Synapses; Synaptic Transmission; Visual Pathways}, Month = {Dec}, Number = {3}, Pages = {955-66}, pmid = {11163279}, Pst = {ppublish}, Title = {Developmental remodeling of the retinogeniculate synapse}, Volume = {28}, Year = {2000}, url = {papers/Chen_Neuron2000.pdf}} @article{Kreitzer:2000, Abstract = {Fluorometric calcium measurements have revealed presynaptic residual calcium (Ca(res)) to be an important regulator of synaptic strength. However, in the mammalian brain, it has not been possible to monitor Ca(res) in fibers that project from one brain region to another. Here, we label neuronal projections by injecting dextran-conjugated calcium indicators into brain nuclei in vivo. Currently available dextran conjugates distort Ca(res) due to their high affinity for calcium. Therefore, we synthesized a low-affinity indicator, fluo-4 dextran, that can more accurately measure the amplitude and time course of Ca(res). We then demonstrate the utility of fluo-4 dextran by measuring Ca(res) at climbing fiber presynaptic terminals. This method promises to facilitate the study of many synapses in the mammalian CNS, both in brain slices and in vivo.}, Author = {Kreitzer, A C and Gee, K R and Archer, E A and Regehr, W G}, Date-Added = {2011-03-07 16:26:18 -0500}, Date-Modified = {2011-09-07 15:09:08 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology;frontiers review; calcium imaging; Technique;retinal wave paper; Fluorescent Dyes;Electric Stimulation;Purkinje Cells;Animals;Aniline Compounds;Rats;Receptors, Presynaptic;Microscopy, Confocal;Dextrans;Spectrometry, Fluorescence;research support, u.s. gov't, p.h.s. ;Rats, Sprague-Dawley;in vitro ;Calcium;21 Neurophysiology;Xanthenes;Nerve Fibers}, Mesh = {Aniline Compounds; Animals; Calcium; Dextrans; Electric Stimulation; Fluorescent Dyes; Microscopy, Confocal; Nerve Fibers; Purkinje Cells; Rats; Rats, Sprague-Dawley; Receptors, Presynaptic; Spectrometry, Fluorescence; Xanthenes}, Month = {Jul}, Number = {1}, Pages = {25-32}, pmid = {10939328}, Pst = {ppublish}, Title = {Monitoring presynaptic calcium dynamics in projection fibers by in vivo loading of a novel calcium indicator}, Volume = {27}, Year = {2000}, url = {papers/Kreitzer_Neuron2000.pdf}} @article{Drew:2010, Abstract = {We present a method to form an optical window in the mouse skull that spans millimeters and is stable for months without causing brain inflammation. This enabled us to repeatedly image blood flow in cortical capillaries of awake mice and determine long-range correlations in speed. We also repeatedly imaged dendritic spines, microglia and angioarchitecture, as well as used illumination to drive motor output via optogenetics and induce microstrokes via photosensitizers.}, Author = {Drew, Patrick J and Shih, Andy Y and Driscoll, Jonathan D and Knutsen, Per Magne and Blinder, Pablo and Davalos, Dimitrios and Akassoglou, Katerina and Tsai, Philbert S and Kleinfeld, David}, Date-Added = {2011-03-07 16:24:12 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology; calcium imaging; Technique;imaging;Optics;microscopy;Multiphoton}, Mesh = {Animals; Blood Flow Velocity; Bone Cements; Brain Ischemia; Cerebral Cortex; Cerebrovascular Circulation; Cerebrum; Mammals; Mice; Microscopy, Confocal; Skull; Wakefulness}, Month = {Dec}, Number = {12}, Pages = {981-4}, pmid = {20966916}, Pst = {ppublish}, Title = {Chronic optical access through a polished and reinforced thinned skull}, Volume = {7}, Year = {2010}, url = {papers/Drew_NatMethods2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1530}} @article{Dombeck:2010, Abstract = {Spatial navigation is often used as a behavioral task in studies of the neuronal circuits that underlie cognition, learning and memory in rodents. The combination of in vivo microscopy with genetically encoded indicators has provided an important new tool for studying neuronal circuits, but has been technically difficult to apply during navigation. Here we describe methods for imaging the activity of neurons in the CA1 region of the hippocampus with subcellular resolution in behaving mice. Neurons that expressed the genetically encoded calcium indicator GCaMP3 were imaged through a chronic hippocampal window. Head-restrained mice performed spatial behaviors in a setup combining a virtual reality system and a custom-built two-photon microscope. We optically identified populations of place cells and determined the correlation between the location of their place fields in the virtual environment and their anatomical location in the local circuit. The combination of virtual reality and high-resolution functional imaging should allow a new generation of studies to investigate neuronal circuit dynamics during behavior.}, Author = {Dombeck, Daniel A and Harvey, Christopher D and Tian, Lin and Looger, Loren L and Tank, David W}, Date-Added = {2011-03-07 16:22:58 -0500}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {optical physiology;calcium imaging; Technique;imaging;in vivo;Optics;microscopy;Multiphoton}, Mesh = {Action Potentials; Animals; Calcium; Cerebral Cortex; Dendrites; Hippocampus; Image Processing, Computer-Assisted; Male; Membrane Potentials; Mice; Mice, Inbred C57BL; Neurons; Nonlinear Dynamics; Patch-Clamp Techniques; Space Perception; Spatial Behavior; Synapsins; Transduction, Genetic; User-Computer Interface}, Month = {Nov}, Number = {11}, Pages = {1433-40}, Pmc = {PMC2967725}, pmid = {20890294}, Pst = {ppublish}, Title = {Functional imaging of hippocampal place cells at cellular resolution during virtual navigation}, Volume = {13}, Year = {2010}, doi = {10.1038/nn.2648}, url = {papers/Dombeck_NatNeurosci2010.pdf}} @article{Mukamel:2009, Abstract = {Recent advances in fluorescence imaging permit studies of Ca(2+) dynamics in large numbers of cells, in anesthetized and awake behaving animals. However, unlike for electrophysiological signals, standardized algorithms for assigning optically recorded signals to individual cells have not yet emerged. Here, we describe an automated sorting procedure that combines independent component analysis and image segmentation for extracting cells' locations and their dynamics with minimal human supervision. In validation studies using simulated data, automated sorting significantly improved estimation of cellular signals compared to conventional analysis based on image regions of interest. We used automated procedures to analyze data recorded by two-photon Ca(2+) imaging in the cerebellar vermis of awake behaving mice. Our analysis yielded simultaneous Ca(2+) activity traces for up to >100 Purkinje cells and Bergmann glia from single recordings. Using this approach, we found microzones of Purkinje cells that were stable across behavioral states and in which synchronous Ca(2+) spiking rose significantly during locomotion.}, Author = {Mukamel, Eran A and Nimmerjahn, Axel and Schnitzer, Mark J}, Date-Added = {2011-03-07 16:21:59 -0500}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology; calcium imaging; Technique;Software;Computational Biology}, Mesh = {Action Potentials; Algorithms; Animals; Calcium; Calcium Signaling; Cerebellum; Diagnostic Imaging; Flow Cytometry; Humans; Image Interpretation, Computer-Assisted; Locomotion; Male; Mice; Mice, Inbred C57BL; Nonlinear Dynamics; Pattern Recognition, Automated; Purkinje Cells; Statistics as Topic}, Month = {Sep}, Number = {6}, Pages = {747-60}, pmid = {19778505}, Pst = {ppublish}, Title = {Automated analysis of cellular signals from large-scale calcium imaging data}, Volume = {63}, Year = {2009}, url = {papers/Mukamel_Neuron2009.pdf}, doi = {10.1016/j.neuron.2009.08.009}} @article{Coombs:2007, Abstract = {Quantitative methods were used to assess dendritic stratification and other structural features of developing mouse retinal ganglion cells from birth to after eye opening. Cells were labeled by transgenic expression of yellow fluorescent protein, DiOlistics or diffusion of DiI, and subsequently imaged in three dimensions on a confocal microscope followed by morphometric analysis of 13 different structural properties. At postnatal day 1 (P1), the dendrites of all cells ramified across the vertical extent of the inner plexiform layer (IPL). By P3/4, dendrites were largely confined to different strata of the IPL. The stratification of dendrites initially reflected a retraction of widely ramifying dendritic processes, but for the most part this was due to the subsequent vertical expansion of the IPL. By P8, distinct cell classes could be recognized, although these had not yet attained adult-like properties. The structural features differentiating cell classes were found to follow three different developmental trends. The mean values of one set of morphological parameters were essentially unchanged throughout postnatal development; another set of measures showed a rapid rise with age to adult values; and a third set of measures first increased with age and later decreased, with the regressive events initiated around the time of eye opening. These findings suggest that the morphological development of retinal ganglion cells is regulated by diverse factors operating during different but overlapping time periods. Our results also suggest that dendritic stratification may be more highly specified in the developing mammalian retina than has been previously realized.}, Author = {Coombs, Julie L and Van Der List, Deborah and Chalupa, Leo M}, Date-Added = {2011-03-07 16:18:07 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {retina;development;mouse;retinal wave paper;optic tectum;superior colliculus}, Mesh = {Animals; Cell Differentiation; Dendrites; Image Processing, Computer-Assisted; Luminescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Retina; Retinal Ganglion Cells}, Month = {Aug}, Number = {6}, Pages = {803-14}, pmid = {17570502}, Pst = {ppublish}, Title = {Morphological properties of mouse retinal ganglion cells during postnatal development}, Volume = {503}, Year = {2007}, url = {papers/Coombs_JCompNeurol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21429}} @article{Tian:2009, Abstract = {Genetically encoded calcium indicators (GECIs) can be used to image activity in defined neuronal populations. However, current GECIs produce inferior signals compared to synthetic indicators and recording electrodes, precluding detection of low firing rates. We developed a single-wavelength GCaMP2-based GECI (GCaMP3), with increased baseline fluorescence (3-fold), increased dynamic range (3-fold) and higher affinity for calcium (1.3-fold). We detected GCaMP3 fluorescence changes triggered by single action potentials in pyramidal cell dendrites, with signal-to-noise ratio and photostability substantially better than those of GCaMP2, D3cpVenus and TN-XXL. In Caenorhabditis elegans chemosensory neurons and the Drosophila melanogaster antennal lobe, sensory stimulation-evoked fluorescence responses were significantly enhanced with GCaMP3 (4-6-fold). In somatosensory and motor cortical neurons in the intact mouse, GCaMP3 detected calcium transients with amplitudes linearly dependent on action potential number. Long-term imaging in the motor cortex of behaving mice revealed large fluorescence changes in imaged neurons over months.}, Author = {Tian, Lin and Hires, S Andrew and Mao, Tianyi and Huber, Daniel and Chiappe, M Eugenia and Chalasani, Sreekanth H and Petreanu, Leopoldo and Akerboom, Jasper and McKinney, Sean A and Schreiter, Eric R and Bargmann, Cornelia I and Jayaraman, Vivek and Svoboda, Karel and Looger, Loren L}, Date-Added = {2011-03-07 16:12:02 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;calcium sensor;voltage sensor;review}, Mesh = {Animals; Brain; Caenorhabditis elegans; Calcium; Cell Line; Drosophila melanogaster; Fluorescence Resonance Energy Transfer; Humans; Mice; Neurons}, Month = {Dec}, Number = {12}, Pages = {875-81}, Pmc = {PMC2858873}, pmid = {19898485}, Pst = {ppublish}, Title = {Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators}, Volume = {6}, Year = {2009}, url = {papers/Tian_NatMethods2009.pdf}, Bdsk-File-2 = {papers/Tian_NatMethods2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1398}} @article{Liu:2010, Abstract = {Optogenetic methods use light to modulate the activities of target cells in vivo. By improving inter- and intracellular trafficking of light-sensitive switch proteins called opsins, Gradinaru et al. (2010) have developed a new generation of optogenetic tools capable of regulating the activity of targeted neurons with exquisite precision and efficiency.}, Author = {Liu, Xu and Tonegawa, Susumu}, Date-Added = {2011-03-07 16:11:25 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {optical physiology; frontiers review; optogenetics; Technique;review}, Month = {Apr}, Number = {1}, Pages = {22-4}, pmid = {20371341}, Pst = {ppublish}, Title = {Optogenetics 3.0}, Volume = {141}, Year = {2010}, url = {papers/Liu_Cell2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2010.03.019}} @article{Rickgauer:2009, Abstract = {We demonstrate that channelrhodopsin-2 (CR), a light-gated ion channel that is conventionally activated by using visible-light excitation, can also be activated by using IR two-photon excitation (TPE). An empirical estimate of CR's two-photon absorption cross-section at lambda = 920 nm is presented, with a value (260 +/- 20 GM) indicating that TPE stimulation of CR photocurrents is not typically limited by intrinsic molecular excitability [1 GM = 10(-50)(cm4 s)/photon]. By using direct physiological measurements of CR photocurrents and a model of ground-state depletion, we evaluate how saturation of CR's current-conducting state influences the spatial resolution of focused TPE photostimulation, and how photocurrents stimulated by using low-power scanning TPE temporally summate. We show that TPE, like visible-light excitation, can be used to stimulate action potentials in cultured CR-expressing neurons.}, Author = {Rickgauer, John Peter and Tank, David W}, Date-Added = {2011-03-07 16:07:00 -0500}, Date-Modified = {2011-09-12 11:19:13 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {optical physiology;frontiers review; optogenetics;Technique}, Mesh = {Cell Line; Electrophysiological Phenomena; Humans; Ion Channels; Patch-Clamp Techniques; Photons; Rhodopsin}, Month = {Sep}, Number = {35}, Pages = {15025-30}, Pmc = {PMC2736443}, pmid = {19706471}, Pst = {ppublish}, Title = {Two-photon excitation of channelrhodopsin-2 at saturation}, Volume = {106}, Year = {2009}, url = {papers/Rickgauer_ProcNatlAcadSciUSA2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0907084106}} @article{Komiyama:2010, Abstract = {Cortical neurons form specific circuits, but the functional structure of this microarchitecture and its relation to behaviour are poorly understood. Two-photon calcium imaging can monitor activity of spatially defined neuronal ensembles in the mammalian cortex. Here we applied this technique to the motor cortex of mice performing a choice behaviour. Head-fixed mice were trained to lick in response to one of two odours, and to withhold licking for the other odour. Mice routinely showed significant learning within the first behavioural session and across sessions. Microstimulation and trans-synaptic tracing identified two non-overlapping candidate tongue motor cortical areas. Inactivating either area impaired voluntary licking. Imaging in layer 2/3 showed neurons with diverse response types in both areas. Activity in approximately half of the imaged neurons distinguished trial types associated with different actions. Many neurons showed modulation coinciding with or preceding the action, consistent with their involvement in motor control. Neurons with different response types were spatially intermingled. Nearby neurons (within approximately 150 mum) showed pronounced coincident activity. These temporal correlations increased with learning within and across behavioural sessions, specifically for neuron pairs with similar response types. We propose that correlated activity in specific ensembles of functionally related neurons is a signature of learning-related circuit plasticity. Our findings reveal a fine-scale and dynamic organization of the frontal cortex that probably underlies flexible behaviour.}, Author = {Komiyama, Takaki and Sato, Takashi R and O'Connor, Daniel H and Zhang, Ying-Xin and Huber, Daniel and Hooks, Bryan M and Gabitto, Mariano and Svoboda, Karel}, Date-Added = {2011-03-07 16:05:18 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; calcium imaging; Technique;in vivo;Motor Cortex;imaging;Multiphoton}, Mesh = {Animals; Axonal Transport; Behavior, Animal; Choice Behavior; Learning; Male; Mice; Mice, Inbred C57BL; Motor Cortex; Motor Neurons; Neural Pathways; Odors; Pyramidal Cells; Reward; Stimulation, Chemical; Time Factors; Tongue}, Month = {Apr}, Number = {7292}, Pages = {1182-6}, pmid = {20376005}, Pst = {ppublish}, Title = {Learning-related fine-scale specificity imaged in motor cortex circuits of behaving mice}, Volume = {464}, Year = {2010}, url = {papers/Komiyama_Nature2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08897}} @article{Histed:2009, Abstract = {For over a century, electrical microstimulation has been the most direct method for causally linking brain function with behavior. Despite this long history, it is still unclear how the activity of neural populations is affected by stimulation. For example, there is still no consensus on where activated cells lie or on the extent to which neural processes such as passing axons near the electrode are also activated. Past studies of this question have proven difficult because microstimulation interferes with electrophysiological recordings, which in any case provide only coarse information about the location of activated cells. We used two-photon calcium imaging, an optical method, to circumvent these hurdles. We found that microstimulation sparsely activates neurons around the electrode, sometimes as far as millimeters away, even at low currents. Our results indicate that the pattern of activated neurons likely arises from the direct activation of axons in a volume tens of microns in diameter.}, Author = {Histed, Mark H and Bonin, Vincent and Reid, R Clay}, Date-Added = {2011-03-07 16:03:05 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {optical physiology; calcium imaging; Technique;in vivo}, Mesh = {Action Potentials; Animals; Cats; Cerebral Cortex; Electric Stimulation; Memory; Mice; Mice, Inbred C57BL; Microelectrodes; Neurons; Rats; Rats, Long-Evans}, Month = {Aug}, Number = {4}, Pages = {508-22}, Pmc = {PMC2874753}, pmid = {19709632}, Pst = {ppublish}, Title = {Direct activation of sparse, distributed populations of cortical neurons by electrical microstimulation}, Volume = {63}, Year = {2009}, url = {papers/Histed_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.07.016}} @article{Baker:2008, Abstract = {Imaging activity of neurons in intact brain tissue was conceived several decades ago and, after many years of development, voltage-sensitive dyes now offer the highest spatial and temporal resolution for imaging neuronal functions in the living brain. Further progress in this field is expected from the emergent development of genetically encoded fluorescent sensors of membrane potential. These fluorescent protein (FP) voltage sensors overcome the drawbacks of organic voltage sensitive dyes such as non-specificity of cell staining and the low accessibility of the dye to some cell types. In a transgenic animal, a genetically encoded sensor could in principle be expressed specifically in any cell type and would have the advantage of staining only the cell population determined by the specificity of the promoter used to drive expression. Here we critically review the current status of these developments.}, Author = {Baker, B J and Mutoh, H and Dimitrov, D and Akemann, W and Perron, A and Iwamoto, Y and Jin, L and Cohen, L B and Isacoff, E Y and Pieribone, V A and Hughes, T and Kn{\"o}pfel, T}, Date-Added = {2011-03-07 16:02:14 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Brain Cell Biol}, Journal-Full = {Brain cell biology}, Keywords = {optical physiology; frontiers review; Technique;voltage sensor}, Mesh = {Animals; Biosensing Techniques; Cell Line; Green Fluorescent Proteins; Humans; Ion Channels; Membrane Potentials; Mice; Mice, Transgenic; Nerve Net}, Month = {Aug}, Number = {1-4}, Pages = {53-67}, Pmc = {PMC2775812}, pmid = {18679801}, Pst = {ppublish}, Title = {Genetically encoded fluorescent sensors of membrane potential}, Volume = {36}, Year = {2008}, url = {papers/Baker_BrainCellBiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s11068-008-9026-7}} @article{Oheim:2001, Abstract = {Light scattering by tissue limits the imaging depth of two-photon microscopy and its use for functional brain imaging in vivo. We investigate the influence of scattering on both fluorescence excitation and collection, and identify tissue and instrument parameters that limit the imaging depth in the brain. (i) In brain slices, we measured that the scattering length at lambda=800 nm is a factor 2 higher in juvenile cortical tissue (P14-P18) than in adult tissue (P90). (ii) In a detection geometry typical for in vivo imaging, we show that the collected fraction of fluorescence drops at large depths, and that it is proportional to the square of the effective angular acceptance of the detection optics. Matching the angular acceptance of the microscope to that of the objective lens can result in a gain of approximately 3 in collection efficiency at large depths (>500 microm). A low-magnification (20x), high-numerical aperture objective (0.95) further increases fluorescence collection by a factor of approximately 10 compared with a standard 60x-63x objective without compromising the resolution. This improvement should allow fluorescence measurements related to neuronal or vascular brain activity at >100 microm deeper than with standard objectives.}, Author = {Oheim, M and Beaurepaire, E and Chaigneau, E and Mertz, J and Charpak, S}, Date-Added = {2011-03-07 16:01:17 -0500}, Date-Modified = {2011-03-07 16:01:55 -0500}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {optical physiology; Technique;Multiphoton;microscopy;Optics}, Mesh = {Aging; Animals; Brain; Cerebral Arteries; Female; Fluorescence; Lenses; Male; Microscopy, Fluorescence; Monte Carlo Method; Neurons; Rats; Rats, Wistar}, Month = {Oct}, Number = {1}, Pages = {29-37}, pmid = {11574117}, Pst = {ppublish}, Title = {Two-photon microscopy in brain tissue: parameters influencing the imaging depth}, Volume = {111}, Year = {2001}, url = {papers/Oheim_JNeurosciMethods2001.pdf}} @article{Barretto:2009, Abstract = {Micro-optics are increasingly used for minimally invasive in vivo imaging, in miniaturized microscopes and in lab-on-a-chip devices. Owing to optical aberrations and lower numerical apertures, a main class of microlens, gradient refractive index lenses, has not achieved resolution comparable to conventional microscopy. Here we describe high-resolution microlenses, and illustrate two-photon imaging of dendritic spines on hippocampal neurons and dual-color nonlinear optical imaging of neuromuscular junctions in live mice.}, Author = {Barretto, Robert P J and Messerschmidt, Bernhard and Schnitzer, Mark J}, Date-Added = {2011-03-07 15:59:19 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology; frontiers review; Technique;optics;microscopy;in vivo}, Mesh = {Animals; Dendritic Spines; Green Fluorescent Proteins; Lenses; Mice; Mice, Transgenic; Microscopy, Fluorescence, Multiphoton; Neuromuscular Junction; Pyramidal Cells; Recombinant Fusion Proteins}, Month = {Jul}, Number = {7}, Pages = {511-2}, Pmc = {PMC2849805}, pmid = {19525959}, Pst = {ppublish}, Title = {In vivo fluorescence imaging with high-resolution microlenses}, Volume = {6}, Year = {2009}, url = {papers/Barretto_NatMethods2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1339}} @article{Lee:2010, Abstract = {Despite a rapidly-growing scientific and clinical brain imaging literature based on functional magnetic resonance imaging (fMRI) using blood oxygenation level-dependent (BOLD) signals, it remains controversial whether BOLD signals in a particular region can be caused by activation of local excitatory neurons. This difficult question is central to the interpretation and utility of BOLD, with major significance for fMRI studies in basic research and clinical applications. Using a novel integrated technology unifying optogenetic control of inputs with high-field fMRI signal readouts, we show here that specific stimulation of local CaMKIIalpha-expressing excitatory neurons, either in the neocortex or thalamus, elicits positive BOLD signals at the stimulus location with classical kinetics. We also show that optogenetic fMRI (of MRI) allows visualization of the causal effects of specific cell types defined not only by genetic identity and cell body location, but also by axonal projection target. Finally, we show that of MRI within the living and intact mammalian brain reveals BOLD signals in downstream targets distant from the stimulus, indicating that this approach can be used to map the global effects of controlling a local cell population. In this respect, unlike both conventional fMRI studies based on correlations and fMRI with electrical stimulation that will also directly drive afferent and nearby axons, this of MRI approach provides causal information about the global circuits recruited by defined local neuronal activity patterns. Together these findings provide an empirical foundation for the widely-used fMRI BOLD signal, and the features of of MRI define a potent tool that may be suitable for functional circuit analysis as well as global phenotyping of dysfunctional circuitry.}, Author = {Lee, Jin Hyung and Durand, Remy and Gradinaru, Viviana and Zhang, Feng and Goshen, Inbal and Kim, Dae-Shik and Fenno, Lief E and Ramakrishnan, Charu and Deisseroth, Karl}, Date-Added = {2011-03-07 15:53:37 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {optical physiology; frontiers review; optogenetics; Technique;fmri}, Mesh = {Action Potentials; Anesthesia; Animals; Brain; Cerebrovascular Circulation; Chlorophyta; Luminescent Measurements; Luminescent Proteins; Magnetic Resonance Imaging; Motor Cortex; Neural Pathways; Neurons; Oxygen; Photic Stimulation; Rats; Rhodopsin; Thalamus}, Month = {Jun}, Number = {7299}, Pages = {788-92}, pmid = {20473285}, Pst = {ppublish}, Title = {Global and local fMRI signals driven by neurons defined optogenetically by type and wiring}, Volume = {465}, Year = {2010}, url = {papers/Lee_Nature2010.pdf}, Bdsk-File-2 = {papers/Lee_Nature2010a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature09108}} @article{Hires:2008, Abstract = {Genetically encoded calcium indicators (GECIs), based on recombinant fluorescent proteins, have been engineered to observe calcium transients in living cells and organisms. Through observation of calcium, these indicators also report neural activity. We review progress in GECI construction and application, particularly toward in vivo monitoring of sparse action potentials (APs). We summarize the extrinsic and intrinsic factors that influence GECI performance. A simple model of GECI response to AP firing demonstrates the relative significance of these factors. We recommend a standardized protocol for evaluating GECIs in a physiologically relevant context. A potential method of simultaneous optical control and recording of neuronal circuits is presented.}, Author = {Hires, S Andrew and Tian, Lin and Looger, Loren L}, Date-Added = {2011-03-07 15:53:37 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Brain Cell Biol}, Journal-Full = {Brain cell biology}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;Genetic Engineering;calcium sensor}, Mesh = {Action Potentials; Animals; Calcium Signaling; Electrophysiology; Luminescent Proteins; Microscopy, Confocal; Neurons; Signal Transduction}, Month = {Aug}, Number = {1-4}, Pages = {69-86}, Pmc = {PMC2755531}, pmid = {18941901}, Pst = {ppublish}, Title = {Reporting neural activity with genetically encoded calcium indicators}, Volume = {36}, Year = {2008}, url = {papers/Hires_BrainCellBiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s11068-008-9029-4}} @article{Sjulson:2007, Abstract = {Optical imaging of physiological events in real time can yield insights into biological function that would be difficult to obtain by other experimental means. However, the detection of all-or-none events, such as action potentials or vesicle fusion events, in noisy single-trial data often requires a careful balance of tradeoffs. The analysis of such experiments, as well as the design of optical reporters and instrumentation for them, is aided by an understanding of the principles of signal detection. This review illustrates these principles, using as an example action potential recording with optical voltage reporters.}, Author = {Sjulson, Lucas and Miesenb{\"o}ck, Gero}, Date-Added = {2011-03-07 15:53:37 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Physiology (Bethesda)}, Journal-Full = {Physiology (Bethesda, Md.)}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;Computational Biology;review}, Mesh = {Action Potentials; Animals; Microscopy, Confocal; Models, Theoretical; Neurons; Optics and Photonics; Photons}, Month = {Feb}, Pages = {47-55}, pmid = {17289930}, Pst = {ppublish}, Title = {Optical recording of action potentials and other discrete physiological events: a perspective from signal detection theory}, Volume = {22}, Year = {2007}, url = {papers/Sjulson_Physiology(Bethesda)2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/physiol.00036.2006}} @article{Rochefort:2009, Abstract = {Eye-opening represents a turning point in the function of the visual cortex. Before eye-opening, the visual cortex is largely devoid of sensory inputs and neuronal activities are generated intrinsically. After eye-opening, the cortex starts to integrate visual information. Here we used in vivo two-photon calcium imaging to explore the developmental changes of the mouse visual cortex by analyzing the ongoing spontaneous activity. We found that before eye-opening, the activity of layer 2/3 neurons consists predominantly of slow wave oscillations. These waves were first detected at postnatal day 8 (P8). Their initial very low frequency (0.01 Hz) gradually increased during development to approximately 0.5 Hz in adults. Before eye-opening, a large fraction of neurons (>75\%) was active during each wave. One day after eye-opening, this dense mode of recruitment changed to a sparse mode with only 36\% of active neurons per wave. This was followed by a progressive decrease during the following weeks, reaching 12\% of active neurons per wave in adults. The possible role of visual experience for this process of sparsification was investigated by analyzing dark-reared mice. We found that sparsification also occurred in these mice, but that the switch from a dense to a sparse activity pattern was delayed by 3-4 days as compared with normally-reared mice. These results reveal a modulatory contribution of visual experience during the first days after eye-opening, but an overall dominating role of intrinsic factors. We propose that the transformation in network activity from dense to sparse is a prerequisite for the changed cortical function at eye-opening.}, Author = {Rochefort, Nathalie L and Garaschuk, Olga and Milos, Ruxandra-Iulia and Narushima, Madoka and Marandi, Nima and Pichler, Bruno and Kovalchuk, Yury and Konnerth, Arthur}, Date-Added = {2011-03-07 15:52:00 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;visual cortex;function;21 Neurophysiology;21 Circuit structure-function;development;21 Activity-development;in vivo;microscopy;Multiphoton}, Mesh = {Animals; Calcium; Electrophysiological Phenomena; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Nervous System Physiological Phenomena; Neurons; Patch-Clamp Techniques; Vision, Ocular; Visual Cortex}, Month = {Sep}, Number = {35}, Pages = {15049-54}, Pmc = {PMC2736444}, pmid = {19706480}, Pst = {ppublish}, Title = {Sparsification of neuronal activity in the visual cortex at eye-opening}, Volume = {106}, Year = {2009}, url = {papers/Rochefort_ProcNatlAcadSciUSA2009.pdf}, Bdsk-File-2 = {papers/Rochefort_ProcNatlAcadSciUSA2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0907660106}} @article{Perron:2009, Abstract = {Electrical signals generated by nerve cells provide the basis of brain function. Whereas single or small numbers of cells are easily accessible using microelectrode recording techniques, less invasive optogenetic methods with spectral properties optimized for in vivo imaging are required for elucidating the operation mechanisms of neuronal circuits composed of large numbers of neurons originating from heterogeneous populations. To this end, we generated and characterized a series of genetically encoded voltage-sensitive fluorescent proteins by molecular fusion of the voltage-sensing domain of Ci-VSP (Ciona intestinalis voltage sensor-containing phosphatase) to red-shifted fluorescent protein operands. We show how these indicator proteins convert voltage-dependent structural rearrangements into a modulation of fluorescence output and demonstrate their applicability for optical recording of individual or simultaneous electrical signals in cultured hippocampal neurons at single-cell resolution without temporal averaging.}, Author = {Perron, Amelie and Mutoh, Hiroki and Launey, Thomas and Kn{\"o}pfel, Thomas}, Date-Added = {2011-03-07 15:49:44 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Chem Biol}, Journal-Full = {Chemistry \& biology}, Keywords = {optical physiology; frontiers review; Technique;review;voltage sensor;}, Mesh = {Animals; Cell Line, Tumor; Electrophysiological Phenomena; Kinetics; Luminescent Proteins; Microelectrodes; Neurons; Phosphoric Monoester Hydrolases; Rats; Recombinant Fusion Proteins}, Month = {Dec}, Number = {12}, Pages = {1268-77}, Pmc = {PMC2818747}, pmid = {20064437}, Pst = {ppublish}, Title = {Red-shifted voltage-sensitive fluorescent proteins}, Volume = {16}, Year = {2009}, url = {papers/Perron_ChemBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.chembiol.2009.11.014}} @article{Knopfel:2006, Abstract = {During the past few decades, optical methods for imaging activity in networks composed of thousands of neurons have been developed. These techniques rely mainly on organic-chemistry-based dyes as indicators of Ca(2+) and membrane potential. However, recently a new generation of probes, genetically encoded fluorescent protein sensors, has emerged for use by physiologists studying the operation of neuronal circuits. We critically review the development of these new probes, and analyze objectives and experimental conditions in which classical probes are likely to prevail and where the fluorescent protein sensors will open paths to previously unexplored territories of functional neuroimaging.}, Author = {Kn{\"o}pfel, Thomas and D{\'\i}ez-Garc{\'\i}a, Javier and Akemann, Walther}, Date-Added = {2011-03-07 15:47:31 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Trends Neurosci}, Journal-Full = {Trends in neurosciences}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;review}, Mesh = {Animals; Biosensing Techniques; Calcium Signaling; Fluorescent Dyes; Genes, Reporter; Genetic Engineering; Humans; Indicators and Reagents; Luminescent Proteins; Models, Neurological; Nerve Net; Neurons; Optics and Photonics; Signal Transduction; Staining and Labeling}, Month = {Mar}, Number = {3}, Pages = {160-6}, pmid = {16443289}, Pst = {ppublish}, Title = {Optical probing of neuronal circuit dynamics: genetically encoded versus classical fluorescent sensors}, Volume = {29}, Year = {2006}, url = {papers/Knöpfel_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.01.004}} @article{Sawinski:2009, Abstract = {We describe a miniaturized head-mounted multiphoton microscope and its use for recording Ca(2+) transients from the somata of layer 2/3 neurons in the visual cortex of awake, freely moving rats. Images contained up to 20 neurons and were stable enough to record continuously for >5 min per trial and 20 trials per imaging session, even as the animal was running at velocities of up to 0.6 m/s. Neuronal Ca(2+) transients were readily detected, and responses to various static visual stimuli were observed during free movement on a running track. Neuronal activity was sparse and increased when the animal swept its gaze across a visual stimulus. Neurons showing preferential activation by specific stimuli were observed in freely moving animals. These results demonstrate that the multiphoton fiberscope is suitable for functional imaging in awake and freely moving animals.}, Author = {Sawinski, Juergen and Wallace, Damian J and Greenberg, David S and Grossmann, Silvie and Denk, Winfried and Kerr, Jason N D}, Date-Added = {2011-03-07 15:46:17 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;in vivo;visual cortex;visual system}, Mesh = {Animals; Calcium; Evoked Potentials, Visual; Male; Microscopy, Fluorescence, Multiphoton; Movement; Neurons; Rats; Rats, Inbred Strains; Visual Cortex}, Month = {Nov}, Number = {46}, Pages = {19557-62}, Pmc = {PMC2773198}, pmid = {19889973}, Pst = {ppublish}, Title = {Visually evoked activity in cortical cells imaged in freely moving animals}, Volume = {106}, Year = {2009}, url = {papers/Sawinski_ProcNatlAcadSciUSA2009.pdf}, Bdsk-File-2 = {papers/Sawinski_ProcNatlAcadSciUSA2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0903680106}} @article{Inglis:2008, Abstract = {Individual locations of many neuronal cell bodies (>10(4)) are needed to enable statistically significant measurements of spatial organization within the brain such as nearest-neighbour and microcolumnarity measurements. In this paper, we introduce an Automated Neuron Recognition Algorithm (ANRA) which obtains the (x, y) location of individual neurons within digitized images of Nissl-stained, 30 microm thick, frozen sections of the cerebral cortex of the Rhesus monkey. Identification of neurons within such Nissl-stained sections is inherently difficult due to the variability in neuron staining, the overlap of neurons, the presence of partial or damaged neurons at tissue surfaces, and the presence of non-neuron objects, such as glial cells, blood vessels, and random artefacts. To overcome these challenges and identify neurons, ANRA applies a combination of image segmentation and machine learning. The steps involve active contour segmentation to find outlines of potential neuron cell bodies followed by artificial neural network training using the segmentation properties (size, optical density, gyration, etc.) to distinguish between neuron and non-neuron segmentations. ANRA positively identifies 86 +/- 5\% neurons with 15 +/- 8\% error (mean +/- SD) on a wide range of Nissl-stained images, whereas semi-automatic methods obtain 80 +/- 7\%/17 +/- 12\%. A further advantage of ANRA is that it affords an unlimited increase in speed from semi-automatic methods, and is computationally efficient, with the ability to recognize approximately 100 neurons per minute using a standard personal computer. ANRA is amenable to analysis of huge photo-montages of Nissl-stained tissue, thereby opening the door to fast, efficient and quantitative analysis of vast stores of archival material that exist in laboratories and research collections around the world.}, Author = {Inglis, A and Cruz, L and Roe, D L and Stanley, H E and Rosene, D L and Urbanc, B}, Date-Added = {2011-03-07 15:41:15 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Microsc}, Journal-Full = {Journal of microscopy}, Keywords = {optical physiology; calcium imaging; Technique;Image Processing;Software;Computational Biology}, Mesh = {Algorithms; Animals; Automation; Cell Nucleolus; Cell Nucleus; Image Processing, Computer-Assisted; Macaca mulatta; Neurons; Nissl Bodies}, Month = {Jun}, Number = {Pt 3}, Pages = {339-52}, Pmc = {PMC2740625}, pmid = {18503659}, Pst = {ppublish}, Title = {Automated identification of neurons and their locations}, Volume = {230}, Year = {2008}, url = {papers/Inglis_JMicrosc2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1365-2818.2008.01992.x}} @article{Grewe:2010, Abstract = {Two-photon calcium imaging of neuronal populations enables optical recording of spiking activity in living animals, but standard laser scanners are too slow to accurately determine spike times. Here we report in vivo imaging in mouse neocortex with greatly improved temporal resolution using random-access scanning with acousto-optic deflectors. We obtained fluorescence measurements from 34-91 layer 2/3 neurons at a 180-490 Hz sampling rate. We detected single action potential-evoked calcium transients with signal-to-noise ratios of 2-5 and determined spike times with near-millisecond precision and 5-15 ms confidence intervals. An automated 'peeling' algorithm enabled reconstruction of complex spike trains from fluorescence traces up to 20-30 Hz frequency, uncovering spatiotemporal trial-to-trial variability of sensory responses in barrel cortex and visual cortex. By revealing spike sequences in neuronal populations on a fast time scale, high-speed calcium imaging will facilitate optical studies of information processing in brain microcircuits.}, Author = {Grewe, Benjamin F and Langer, Dominik and Kasper, Hansj{\"o}rg and Kampa, Bj{\"o}rn M and Helmchen, Fritjof}, Date-Added = {2011-03-07 15:39:08 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;microscopy;optics;in vivo}, Mesh = {Action Potentials; Algorithms; Animals; Calcium Signaling; Evoked Potentials; Imaging, Three-Dimensional; Mice; Microscopy, Confocal; Microscopy, Fluorescence; Neocortex; Neurons; Visual Cortex}, Month = {May}, Number = {5}, Pages = {399-405}, pmid = {20400966}, Pst = {ppublish}, Title = {High-speed in vivo calcium imaging reveals neuronal network activity with near-millisecond precision}, Volume = {7}, Year = {2010}, url = {papers/Grewe_NatMethods2010.pdf}, Bdsk-File-2 = {papers/Grewe_NatMethods2010a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1453}} @article{Lutcke:2010, Abstract = {Fluorescent calcium (Ca(2+)) indicator proteins (FCIPs) are promising tools for functional imaging of cellular activity in living animals. However, they have still not reached their full potential for in vivo imaging of neuronal activity due to limitations in expression levels, dynamic range, and sensitivity for reporting action potentials. Here, we report that viral expression of the ratiometric Ca(2+) sensor yellow cameleon 3.60 (YC3.60) in pyramidal neurons of mouse barrel cortex enables in vivo measurement of neuronal activity with high dynamic range and sensitivity across multiple spatial scales. By combining juxtacellular recordings and two-photon imaging in vitro and in vivo, we demonstrate that YC3.60 can resolve single action potential (AP)-evoked Ca(2+) transients and reliably reports bursts of APs with negligible saturation. Spontaneous and whisker-evoked Ca(2+) transients were detected in individual apical dendrites and somata as well as in local neuronal populations. Moreover, bulk measurements using wide-field imaging or fiber-optics revealed sensory-evoked YC3.60 signals in large areas of the barrel field. Fiber-optic recordings in particular enabled measurements in awake, freely moving mice and revealed complex Ca(2+) dynamics, possibly reflecting different behavior-related brain states. Viral expression of YC3.60 - in combination with various optical techniques - thus opens a multitude of opportunities for functional studies of the neural basis of animal behavior, from dendrites to the levels of local and large-scale neuronal populations.}, Author = {L{\"u}tcke, Henry and Murayama, Masanori and Hahn, Thomas and Margolis, David J and Astori, Simone and Zum Alten Borgloh, Stephan Meyer and G{\"o}bel, Werner and Yang, Ying and Tang, Wannan and K{\"u}gler, Sebastian and Sprengel, Rolf and Nagai, Takeharu and Miyawaki, Atsushi and Larkum, Matthew E and Helmchen, Fritjof and Hasan, Mazahir T}, Date-Added = {2011-03-07 15:38:00 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Front Neural Circuits}, Journal-Full = {Frontiers in neural circuits}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;in vivo}, Pages = {9}, Pmc = {PMC2866455}, pmid = {20461230}, Pst = {epublish}, Title = {Optical recording of neuronal activity with a genetically-encoded calcium indicator in anesthetized and freely moving mice}, Volume = {4}, Year = {2010}, url = {papers/Lütcke_FrontNeuralCircuits2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncir.2010.00009}} @article{Kuchibhotla:2009, Abstract = {Although senile plaques focally disrupt neuronal health, the functional response of astrocytes to Alzheimer's disease pathology is unknown. Using multiphoton fluorescence lifetime imaging microscopy in vivo, we quantitatively imaged astrocytic calcium homeostasis in a mouse model of Alzheimer's disease. Resting calcium was globally elevated in the astrocytic network, but was independent of proximity to individual plaques. Time-lapse imaging revealed that calcium transients in astrocytes were more frequent, synchronously coordinated across long distances, and uncoupled from neuronal activity. Furthermore, rare intercellular calcium waves were observed, but only in mice with amyloid-beta plaques, originating near plaques and spreading radially at least 200 micrometers. Thus, although neurotoxicity is observed near amyloid-beta deposits, there exists a more general astrocyte-based network response to focal pathology.}, Author = {Kuchibhotla, Kishore V and Lattarulo, Carli R and Hyman, Bradley T and Bacskai, Brian J}, Date-Added = {2011-03-07 15:32:23 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique}, Mesh = {Alzheimer Disease; Amyloid beta-Peptides; Animals; Astrocytes; Calcium; Calcium Signaling; Disease Models, Animal; Homeostasis; Humans; Mice; Mice, Transgenic; Microscopy, Fluorescence, Multiphoton; Neurons; Plaque, Amyloid}, Month = {Feb}, Number = {5918}, Pages = {1211-5}, Pmc = {PMC2884172}, pmid = {19251629}, Pst = {ppublish}, Title = {Synchronous hyperactivity and intercellular calcium waves in astrocytes in Alzheimer mice}, Volume = {323}, Year = {2009}, url = {papers/Kuchibhotla_Science2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1169096}} @article{Gradinaru:2010, Abstract = {Optogenetic technologies employ light to control biological processes within targeted cells in vivo with high temporal precision. Here, we show that application of molecular trafficking principles can expand the optogenetic repertoire along several long-sought dimensions. Subcellular and transcellular trafficking strategies now permit (1) optical regulation at the far-red/infrared border and extension of optogenetic control across the entire visible spectrum, (2) increased potency of optical inhibition without increased light power requirement (nanoampere-scale chloride-mediated photocurrents that maintain the light sensitivity and reversible, step-like kinetic stability of earlier tools), and (3) generalizable strategies for targeting cells based not only on genetic identity, but also on morphology and tissue topology, to allow versatile targeting when promoters are not known or in genetically intractable organisms. Together, these results illustrate use of cell-biological principles to enable expansion of the versatile fast optogenetic technologies suitable for intact-systems biology and behavior.}, Author = {Gradinaru, Viviana and Zhang, Feng and Ramakrishnan, Charu and Mattis, Joanna and Prakash, Rohit and Diester, Ilka and Goshen, Inbal and Thompson, Kimberly R and Deisseroth, Karl}, Date-Added = {2011-03-07 15:32:23 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {optical physiology; frontiers review; optogenetics; Technique}, Mesh = {Animals; Cells, Cultured; Genetic Techniques; Hippocampus; Humans; Light; Neurons; Opsonin Proteins; Rats; Systems Biology}, Month = {Apr}, Number = {1}, Pages = {154-65}, pmid = {20303157}, Pst = {ppublish}, Title = {Molecular and cellular approaches for diversifying and extending optogenetics}, Volume = {141}, Year = {2010}, url = {papers/Gradinaru_Cell2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2010.02.037}} @article{Dreosti:2009, Abstract = {To image synaptic activity within neural circuits, we tethered the genetically encoded calcium indicator (GECI) GCaMP2 to synaptic vesicles by fusion to synaptophysin. The resulting reporter, SyGCaMP2, detected the electrical activity of neurons with two advantages over existing cytoplasmic GECIs: it identified the locations of synapses and had a linear response over a wider range of spike frequencies. Simulations and experimental measurements indicated that linearity arises because SyGCaMP2 samples the brief calcium transient passing through the presynaptic compartment close to voltage-sensitive calcium channels rather than changes in bulk calcium concentration. In vivo imaging in zebrafish demonstrated that SyGCaMP2 can assess electrical activity in conventional synapses of spiking neurons in the optic tectum and graded voltage signals transmitted by ribbon synapses of retinal bipolar cells. Localizing a GECI to synaptic terminals provides a strategy for monitoring activity across large groups of neurons at the level of individual synapses.}, Author = {Dreosti, Elena and Odermatt, Benjamin and Dorostkar, Mario M and Lagnado, Leon}, Date-Added = {2011-03-07 15:32:23 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique}, Mesh = {Action Potentials; Animals; Calcium; Synapses; Zebrafish}, Month = {Dec}, Number = {12}, Pages = {883-9}, Pmc = {PMC2859341}, pmid = {19898484}, Pst = {ppublish}, Title = {A genetically encoded reporter of synaptic activity in vivo}, Volume = {6}, Year = {2009}, url = {papers/Dreosti_NatMethods2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1399}} @article{Golshani:2009, Abstract = {During neocortical development, neurons exhibit highly synchronized patterns of spontaneous activity, with correlated bursts of action potential firing dominating network activity. This early activity is eventually replaced by more sparse and decorrelated firing of cortical neurons, which modeling studies predict is a network state that is better suited for efficient neural coding. The precise time course and mechanisms of this crucial transition in cortical network activity have not been characterized in vivo. We used in vivo two-photon calcium imaging in combination with whole-cell recordings in both unanesthetized and anesthetized mice to monitor how spontaneous activity patterns in ensembles of layer 2/3 neurons of barrel cortex mature during postnatal development. We find that, as early as postnatal day 4, activity is highly synchronous within local clusters of neurons. At the end of the second postnatal week, neocortical networks undergo a transition to a much more desynchronized state that lacks a clear spatial structure. Strikingly, deprivation of sensory input from the periphery had no effect on the time course of this transition. Therefore, developmental desynchronization of spontaneous neuronal activity is a fundamental network transition in the neocortex that appears to be intrinsically generated.}, Author = {Golshani, Peyman and Gon{\c c}alves, J Tiago and Khoshkhoo, Sattar and Mostany, Ricardo and Smirnakis, Stelios and Portera-Cailliau, Carlos}, Date-Added = {2011-03-07 15:32:23 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique}, Mesh = {Action Potentials; Animals; Animals, Newborn; Cortical Synchronization; Female; Male; Mice; Mice, Inbred C57BL; Neocortex; Nerve Net; Neuronal Plasticity}, Month = {Sep}, Number = {35}, Pages = {10890-9}, Pmc = {PMC2771734}, pmid = {19726647}, Pst = {ppublish}, Title = {Internally mediated developmental desynchronization of neocortical network activity}, Volume = {29}, Year = {2009}, url = {papers/Golshani_JNeurosci2009.pdf}, Bdsk-File-2 = {papers/Golshani_JNeurosci2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2012-09.2009}} @article{Griesbeck:2004, Abstract = {The exploitation of green fluorescent protein-based biosensors promises to revolutionize functional imaging of the nervous system. Various approaches have created a multitude of reporters of neuronal activity and of activation of biochemical signaling pathways. Although the number of different probes has increased significantly, the critical step remains to bring these probes from the cuvette through the imaging of single cells to the imaging of whole organisms in vivo. The recent development of new genetically encoded sensors and their functional expression in model organisms are encouraging signs that the field is moving ahead in this direction.}, Author = {Griesbeck, Oliver}, Date-Added = {2011-03-07 15:32:23 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique}, Mesh = {Animals; Animals, Genetically Modified; Biosensing Techniques; Calcium Signaling; Cell Communication; Fluorescent Dyes; Green Fluorescent Proteins; Humans; Indicators and Reagents; Mutagenesis; Nervous System}, Month = {Oct}, Number = {5}, Pages = {636-41}, pmid = {15464898}, Pst = {ppublish}, Title = {Fluorescent proteins as sensors for cellular functions}, Volume = {14}, Year = {2004}, url = {papers/Griesbeck_CurrOpinNeurobiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2004.08.002}} @article{Wallace:2008, Abstract = {Measurement of population activity with single-action-potential, single-neuron resolution is pivotal for understanding information representation and processing in the brain and how the brain's responses are altered by experience. Genetically encoded indicators of neuronal activity allow long-term, cell type-specific expression. Fluorescent Ca2+ indicator proteins (FCIPs), a main class of reporters of neural activity, initially suffered, in particular, from an inability to report single action potentials in vivo. Although suboptimal Ca2+-binding dynamics and Ca2+-induced fluorescence changes in FCIPs are important factors, low levels of expression also seem to play a role. Here we report that delivering D3cpv, an improved fluorescent resonance energy transfer-based FCIP, using a recombinant adeno-associated virus results in expression sufficient to detect the Ca2+ transients that accompany single action potentials. In upper-layer cortical neurons, we were able to detect transients associated with single action potentials firing at rates of <1 Hz, with high reliability, from in vivo recordings in living mice.}, Author = {Wallace, Damian J and Meyer zum Alten Borgloh, Stephan and Astori, Simone and Yang, Ying and Bausen, Melanie and K{\"u}gler, Sebastian and Palmer, Amy E and Tsien, Roger Y and Sprengel, Rolf and Kerr, Jason N D and Denk, Winfried and Hasan, Mazahir T}, Date-Added = {2011-03-07 15:32:23 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;calcium sensor}, Mesh = {Action Potentials; Animals; Brain; Calcium; Calmodulin; Cells, Cultured; Dependovirus; Fluorescence Resonance Energy Transfer; Hippocampus; Mice; Mice, Inbred C57BL; Recombinant Fusion Proteins; Somatosensory Cortex; Synapses}, Month = {Sep}, Number = {9}, Pages = {797-804}, pmid = {19160514}, Pst = {ppublish}, Title = {Single-spike detection in vitro and in vivo with a genetic Ca2+ sensor}, Volume = {5}, Year = {2008}, url = {papers/Wallace_NatMethods2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1242}} @article{Rothermel:2009, Abstract = {Pseudorabies virus (PrV) strains such as PrV-Bartha and its marker protein-expressing variants have been used in numerous studies as retrograde transneuronal tracing tools, defining the synaptic organization of mammalian neuronal circuits. However, the possibilities for functional examination of virus-infected neurons are limited to electrophysiological approaches or bulk loading strategies using calcium-sensitive dyes. Herein we report the generation and functional characterization of three PrV-Bartha-derived recombinant virus mutants that express different fluorescent calcium indicator proteins (FCIPs). All three generated virus recombinants are able to infect murine trigeminal neurons and express the corresponding FCIP (GCaMP2, camgaroo-2, or inverse pericam). Functionality of these virally expressed constructs was verified by using confocal Ca-imaging technologies. These FCIP-expressing virus recombinants provide a new tool for the functional analysis of whole circuits of synaptically connected neurons in vitro and in vivo.}, Author = {Rothermel, Markus and Brunert, Daniela and Klupp, Barbara G and Luebbert, Matthias and Mettenleiter, Thomas C and Hatt, Hanns}, Date-Added = {2011-03-07 15:25:33 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurovirol}, Journal-Full = {Journal of neurovirology}, Keywords = {optical physiology;optical imaging;frontiers review;viral;viral gene transfer;Genetic Engineering;23 Technique}, Mesh = {Animals; Calcium; Fluorescent Dyes; Herpesvirus 1, Suid; Mice; Neural Pathways; Neuroanatomy; Neurons; Neurophysiology; Patch-Clamp Techniques; Pseudorabies; Recombinant Fusion Proteins; Synapses; Trigeminal Ganglion}, Month = {Dec}, Number = {5-6}, Pages = {458-64}, pmid = {20105103}, Pst = {ppublish}, Title = {Advanced tracing tools: functional neuronal expression of virally encoded fluorescent calcium indicator proteins}, Volume = {15}, Year = {2009}, url = {papers/Rothermel_JNeurovirol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3109/13550280903473460}} @article{Kanold:2004, Abstract = {Subplate neurons are a transient population of neurons in the brain forming one of the first functional cortical circuits. Past experiments have demonstrated their importance in growth of thalamocortical afferents into the cortical plate and later segregation of thalamocortical afferents. Recently, subplate neurons have been shown to be required for the functional maturation of both thalamocortical connections and mature visual responses in visual cortex. These findings suggest that thalamocortical afferents might not segregate properly in the absence of subplate neurons because the thalamocortical synapse does not mature. Subplate neurons are unique in that they form a circuit that appears to promote synaptic scaling and maturation. Although the precise contribution of subplate neurons within the context of cortical development is unknown, they might play an early role in providing thalamic input to cortex that then interacts with learning rules governing synaptic strengthening at the thalamocortical synapse. Because they appear to play multiple key roles at different stages of development, subplate neurons might also play a role in the pathology of developmental disorders, such as epilepsy and schizophrenia.}, Author = {Kanold, Patrick O}, Date-Added = {2011-03-07 15:22:02 -0500}, Date-Modified = {2011-03-07 15:22:56 -0500}, Journal = {Neuroreport}, Journal-Full = {Neuroreport}, Keywords = {21 Activity-development;Spontaneous activity;visual cortex;development;axon guidance;10 circuit formation;Circuits;connectivity}, Mesh = {Animals; Cerebral Cortex; Humans; Nerve Net; Neural Pathways; Neurons; Thalamus}, Month = {Oct}, Number = {14}, Pages = {2149-53}, pmid = {15371723}, Pst = {ppublish}, Title = {Transient microcircuits formed by subplate neurons and their role in functional development of thalamocortical connections}, Volume = {15}, Year = {2004}, url = {papers/Kanold_Neuroreport2004.pdf}} @article{Cingolani:2008, Abstract = {At synapses, cell adhesion molecules (CAMs) provide the molecular framework for coordinating signaling events across the synaptic cleft. Among synaptic CAMs, the integrins, receptors for extracellular matrix proteins and counterreceptors on adjacent cells, are implicated in synapse maturation and plasticity and memory formation. However, little is known about the molecular mechanisms of integrin action at central synapses. Here, we report that postsynaptic beta3 integrins control synaptic strength by regulating AMPA receptors (AMPARs) in a subunit-specific manner. Pharmacological perturbation targeting beta3 integrins promotes endocytosis of GluR2-containing AMPARs via Rap1 signaling, and expression of beta3 integrins produces robust changes in the abundance and composition of synaptic AMPARs without affecting dendritic spine structure. Importantly, homeostatic synaptic scaling induced by activity deprivation elevates surface expression of beta3 integrins, and in turn, beta3 integrins are required for synaptic scaling. Our findings demonstrate a key role for integrins in the feedback regulation of excitatory synaptic strength.}, Author = {Cingolani, Lorenzo A and Thalhammer, Agnes and Yu, Lily M Y and Catalano, Myriam and Ramos, Timothy and Colicos, Michael A and Goda, Yukiko}, Date-Added = {2011-03-07 15:17:56 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;development;homeostatic plasticity;Critical Period;hebbian;plasticity;Synapses;synaptic scaling;Cell Adhesion;cell interaction;molecules;Genes}, Mesh = {Animals; Bicyclo Compounds, Heterocyclic; Chelating Agents; Egtazic Acid; Endocytosis; Excitatory Amino Acids; Excitatory Postsynaptic Potentials; Gene Expression Regulation; Hippocampus; Integrin beta3; Mice; Mice, Knockout; Neural Inhibition; Neurons; Patch-Clamp Techniques; Peptides; Platelet Aggregation Inhibitors; Presynaptic Terminals; Rats; Receptors, AMPA; Synapses; Thiazolidines; Time Factors; Transfection; rap1 GTP-Binding Proteins}, Month = {Jun}, Number = {5}, Pages = {749-62}, Pmc = {PMC2446609}, pmid = {18549786}, Pst = {ppublish}, Title = {Activity-dependent regulation of synaptic AMPA receptor composition and abundance by beta3 integrins}, Volume = {58}, Year = {2008}, url = {papers/Cingolani_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.04.011}} @article{Maffei:2008, Abstract = {Sensory experience is crucial for shaping the cortical microcircuit during development and is thought to modify network function through several forms of Hebbian and homeostatic plasticity. Where and when these different forms of plasticity are expressed at particular synapse types within cortical microcircuits, and how they interact, is poorly understood. Here we investigated how two different visual deprivation paradigms, lid suture (LS) and intraocular TTX, affect the local microcircuit within layer 2/3 of rat visual cortex during the classical critical period for visual system plasticity. Both forms of visual deprivation produced a compensatory increase in the spontaneous firing of layer 2/3 pyramidal neurons in acute slices derived from monocular visual cortex. TTX increased spontaneous activity through an increase in the excitation/inhibition (E/I) balance within layer 2/3. In contrast, LS decreased the E/I balance by strongly depressing excitatory transmission, and the homeostatic increase in spontaneous activity was instead achieved through an increase in the intrinsic excitability of layer 2/3 pyramidal neurons. The microcircuit in layer 2/3 can thus use different forms of homeostatic plasticity to compensate for the loss of visual drive, depending on the specific demands produced by visual experience. The existence of multiple, partially redundant forms of homeostatic plasticity may ensure that network compensation can be achieved in response to a wide range of sensory perturbations.}, Author = {Maffei, Arianna and Turrigiano, Gina G}, Date-Added = {2011-03-07 15:17:56 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;development;homeostatic plasticity;Critical Period;hebbian;plasticity;Synapses;synaptic scaling;visual cortex;visual system;Sensory Deprivation}, Mesh = {Animals; Animals, Newborn; Excitatory Postsynaptic Potentials; Homeostasis; Nerve Net; Neuronal Plasticity; Rats; Rats, Long-Evans; Sensory Deprivation; Visual Cortex}, Month = {Apr}, Number = {17}, Pages = {4377-84}, Pmc = {PMC2655203}, pmid = {18434516}, Pst = {ppublish}, Title = {Multiple modes of network homeostasis in visual cortical layer 2/3}, Volume = {28}, Year = {2008}, url = {papers/Maffei_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5298-07.2008}} @article{Turrigiano:2004a, Author = {Turrigiano, Gina G and Nelson, Sacha B}, Date-Added = {2011-03-07 15:17:56 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {21 Activity-development;development;homeostatic plasticity;Critical Period;hebbian;plasticity;Synapses;synaptic scaling;visual cortex;visual system;Sensory Deprivation}, Mesh = {Animals; Homeostasis; Humans; Nervous System; Neural Pathways; Neuronal Plasticity; Receptors, Neurotransmitter; Synapses; Synaptic Transmission}, Month = {Feb}, Number = {2}, Pages = {97-107}, pmid = {14735113}, Pst = {ppublish}, Title = {Homeostatic plasticity in the developing nervous system}, Volume = {5}, Year = {2004}, url = {papers/Turrigiano_NatRevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1327}} @article{Renart:2003, Abstract = {The concept of bell-shaped persistent neural activity represents a cornerstone of the theory for the internal representation of analog quantities, such as spatial location or head direction. Previous models, however, relied on the unrealistic assumption of network homogeneity. We investigate this issue in a network model where fine tuning of parameters is destroyed by heterogeneities in cellular and synaptic properties. Heterogeneities result in the loss of stored spatial information in a few seconds. Accurate encoding is recovered when a homeostatic mechanism scales the excitatory synapses to each cell to compensate for the heterogeneity in cellular excitability and synaptic inputs. Moreover, the more realistic model produces a wide diversity of tuning curves, as commonly observed in recordings from prefrontal neurons. We conclude that recurrent attractor networks in conjunction with appropriate homeostatic mechanisms provide a robust, biologically plausible theoretical framework for understanding the neural circuit basis of spatial working memory.}, Author = {Renart, Alfonso and Song, Pengcheng and Wang, Xiao-Jing}, Date-Added = {2011-03-07 15:17:56 -0500}, Date-Modified = {2011-03-07 15:21:40 -0500}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;homeostatic plasticity;Critical Period;hebbian;plasticity;Synapses;synaptic scaling;Models;Computational Biology;Theoretical}, Mesh = {Action Potentials; Animals; Cerebral Cortex; Homeostasis; Humans; Memory, Short-Term; Models, Neurological; Nerve Net; Neural Pathways; Neurons; Nonlinear Dynamics; Reproducibility of Results; Space Perception; Synapses; Synaptic Transmission}, Month = {May}, Number = {3}, Pages = {473-85}, pmid = {12741993}, Pst = {ppublish}, Title = {Robust spatial working memory through homeostatic synaptic scaling in heterogeneous cortical networks}, Volume = {38}, Year = {2003}, url = {papers/Renart_Neuron2003.pdf}} @article{Akemann:2009, Abstract = {The relatively simple and highly modular circuitry of the cerebellum raised expectations decades ago that a realistic computational model of cerebellar circuit operations would be feasible, and prove insightful for unraveling cerebellar information processing. To this end, the biophysical properties of most cerebellar cell types and their synaptic connections have been well characterized and integrated into realistic single cell models. Furthermore, large scale models of cerebellar circuits that extrapolate from single cell properties to circuit dynamics have been constructed. While the development of single cell models have been constrained by microelectrode recordings, guidance and validation as these models are scaled up to study network interactions requires an experimental methodology capable of monitoring cerebellar dynamics at the population level. Here we review the potential of optical imaging techniques to serve this purpose.}, Author = {Akemann, Walther and Middleton, Steven J and Kn{\"o}pfel, Thomas}, Date-Added = {2011-03-07 15:09:03 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Front Cell Neurosci}, Journal-Full = {Frontiers in cellular neuroscience}, Keywords = {optogenetics;imaging;in vivo;review;optical imaging;frontiers review;23 Technique}, Pages = {5}, Pmc = {PMC2718781}, pmid = {19649169}, Pst = {ppublish}, Title = {Optical imaging as a link between cellular neurophysiology and circuit modeling}, Volume = {3}, Year = {2009}, url = {papers/Akemann_FrontCellNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/neuro.03.005.2009}} @article{Barabasi:1999, Abstract = {Systems as diverse as genetic networks or the World Wide Web are best described as networks with complex topology. A common property of many large networks is that the vertex connectivities follow a scale-free power-law distribution. This feature was found to be a consequence of two generic mechanisms: (i) networks expand continuously by the addition of new vertices, and (ii) new vertices attach preferentially to sites that are already well connected. A model based on these two ingredients reproduces the observed stationary scale-free distributions, which indicates that the development of large networks is governed by robust self-organizing phenomena that go beyond the particulars of the individual systems.}, Author = {Barabasi and Albert}, Date-Added = {2011-03-07 15:06:43 -0500}, Date-Modified = {2011-03-07 15:08:06 -0500}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Spontaneous activity;self organization;graph theory;Computational Biology;Theoretical;evolutionary dynamics;09 Evolutionary dynamics}, Month = {Oct}, Number = {5439}, Pages = {509-12}, pmid = {10521342}, Pst = {ppublish}, Title = {Emergence of scaling in random networks}, Volume = {286}, Year = {1999}, url = {papers/Barabasi_Science1999.pdf}} @article{Yassin:2010, Abstract = {Unbiased methods to assess the firing activity of individual neurons in the neocortex have revealed that a large proportion of cells fire at extremely low rates (<0.1 Hz), both in their spontaneous and evoked activity. Thus, firing in neocortical networks appears to be dominated by a small population of highly active neurons. Here, we use a fosGFP transgenic mouse to examine the properties of cells with a recent history of elevated activity. FosGFP-expressing layer 2/3 pyramidal cells fired at higher rates compared to fosGFP(-) neurons, both in vivo and in vitro. Elevated activity could be attributed to increased excitatory and decreased inhibitory drive to fosGFP(+) neurons. Paired-cell recordings indicated that fosGFP(+) neurons had a greater likelihood of being connected to each other. These findings indicate that highly active, interconnected neuronal ensembles are present in the neocortex and suggest these cells may play a role in the encoding of sensory information. VIDEO ABSTRACT:}, Author = {Yassin, Lina and Benedetti, Brett L and Jouhanneau, Jean-S{\'e}bastien and Wen, Jing A and Poulet, James F A and Barth, Alison L}, Date-Added = {2011-03-07 15:02:22 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Neurophysiology;21 Circuit structure-function;21 Activity-development;Imaging;microscopy;Multiphoton;23 Technique;frontiers review}, Mesh = {Action Potentials; Animals; Animals, Newborn; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neocortex; Nerve Net; Neurons}, Month = {Dec}, Number = {6}, Pages = {1043-50}, Pmc = {PMC3022325}, pmid = {21172607}, Pst = {ppublish}, Title = {An embedded subnetwork of highly active neurons in the neocortex}, Volume = {68}, Year = {2010}, url = {papers/Yassin_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.11.029}} @article{Linden:2009, Abstract = {Manipulations of activity in one retina can profoundly affect binocular connections in the visual cortex. Retinal activity is relayed to the cortex by the dorsal lateral geniculate nucleus (dLGN). We compared the qualities and amount of activity in the dLGN following monocular eyelid closure and monocular retinal inactivation in awake mice. Our findings substantially alter the interpretation of previous studies and define the afferent activity patterns that trigger cortical plasticity.}, Author = {Linden, Monica L and Heynen, Arnold J and Haslinger, Robert H and Bear, Mark F}, Date-Added = {2011-03-07 15:00:09 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Activity-development;experience dependent plasticity;Critical Period;plasticity;Competitive Behavior;Cooperative Behavior;visual cortex;visual system;Sensory Deprivation;21 Neurophysiology}, Mesh = {Action Potentials; Anesthetics, Local; Animals; Brain Mapping; Evoked Potentials, Visual; Functional Laterality; Geniculate Bodies; Hypnotics and Sedatives; Mice; Neuronal Plasticity; Neurons; Pentobarbital; Photic Stimulation; Retina; Sensory Deprivation; Tetrodotoxin; Time Factors; Vision, Monocular; Visual Cortex; Visual Pathways; Visual Perception; Wakefulness}, Month = {Apr}, Number = {4}, Pages = {390-2}, Pmc = {PMC2669755}, pmid = {19252494}, Pst = {ppublish}, Title = {Thalamic activity that drives visual cortical plasticity}, Volume = {12}, Year = {2009}, url = {papers/Linden_NatNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2284}} @article{Weible:2010, Abstract = {Understanding how neural circuits work requires a detailed knowledge of cellular-level connectivity. Our current understanding of neural circuitry is limited by the constraints of existing tools for transsynaptic tracing. Some of the most intractable problems are a lack of cellular specificity of uptake, transport across multiple synaptic steps conflating direct and indirect inputs, and poor labeling of minor inputs. We used a novel combination of transgenic mouse technology and a recently developed tracing system based on rabies virus (Wickersham et al., 2007a,b) to overcome all three constraints. Because the virus requires transgene expression for both initial infection and subsequent retrograde transsynaptic infection, we created several lines of mice that express these genes in defined cell types using the tetracycline-dependent transactivator system (Mansuy and Bujard, 2000). Fluorescent labeling from viral replication is thereby restricted to defined neuronal cell types and their direct monosynaptic inputs. Because viral replication does not depend on transgene expression, it provides robust amplification of signal in presynaptic neurons regardless of input strength. We injected virus into transgenic crosses expressing the viral transgenes in specific cell types of the hippocampus formation to demonstrate cell-specific infection and monosynaptic retrograde transport of virus, which strongly labels even minor inputs. Such neuron-specific transgenic complementation of recombinant rabies virus holds great promise for obtaining cellular-resolution wiring diagrams of the mammalian CNS.}, Author = {Weible, Aldis P and Schwarcz, Leslie and Wickersham, Ian R and Deblander, Leah and Wu, Haiyan and Callaway, Edward M and Seung, H Sebastian and Kentros, Clifford G}, Date-Added = {2011-03-07 14:56:13 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {viral;Gene Therapy;Genetic Engineering;Synapses;connectivity;imaging;23 Technique;cell interaction;Cell Adhesion;Trans-synaptic;frontiers review}, Mesh = {Animals; Gene Deletion; Gene Expression Regulation, Viral; Green Fluorescent Proteins; Hippocampus; Mice; Mice, Transgenic; Mutation; Neurons; RNA, Messenger; Rabies virus; Recombination, Genetic; Synapses; Transgenes; Viral Envelope Proteins}, Month = {Dec}, Number = {49}, Pages = {16509-13}, pmid = {21147990}, Pst = {ppublish}, Title = {Transgenic targeting of recombinant rabies virus reveals monosynaptic connectivity of specific neurons}, Volume = {30}, Year = {2010}, url = {papers/Weible_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2442-10.2010}} @article{Wang:2010a, Abstract = {The mouse is a promising model in the study of visual system function and development because of available genetic tools. However, a quantitative analysis of visual receptive field properties had not been performed in the mouse superior colliculus (SC) despite its importance in mouse vision and its usefulness in developmental studies. We have made single-unit extracellular recordings from superficial layers of the SC in urethane-anesthetized C57BL/6 mice. We first map receptive fields with flashing spot stimuli and show that most SC neurons have spatially overlapped ON and OFF subfields. With drifting sinusoidal gratings, we then determine the tuning properties of individual SC neurons, including selectivity for stimulus direction and orientation, spatial frequency tuning, temporal frequency tuning, response linearity, and size preference. A wide range of receptive field sizes and selectivity are observed across the population and in various subtypes of SC neurons identified morphologically. In particular, orientation-selective responses are discovered in the mouse SC, and they are not affected by cortical lesion or long-term visual deprivation. However, ON/OFF characteristics and spatial frequency tuning of SC neurons are influenced by cortical inputs and require visual experience during development. Together, our results provide essential information for future investigations on the functional development of the superior colliculus.}, Author = {Wang, Lupeng and Sarnaik, Rashmi and Rangarajan, Krsna and Liu, Xiaorong and Cang, Jianhua}, Date-Added = {2011-03-07 14:54:28 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology;Spontaneous activity;retina;visual cortex;visual system;Superior Colliculus;optic tectum;function;in vivo}, Mesh = {Animals; Animals, Newborn; Brain Mapping; Female; Functional Laterality; Lysine; Male; Mice; Mice, Inbred C57BL; Neurons; Orientation; Photic Stimulation; Psychophysics; Statistics as Topic; Superior Colliculi; Visual Fields; Visual Pathways; Visual Perception}, Month = {Dec}, Number = {49}, Pages = {16573-84}, pmid = {21147997}, Pst = {ppublish}, Title = {Visual receptive field properties of neurons in the superficial superior colliculus of the mouse}, Volume = {30}, Year = {2010}, url = {papers/Wang_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3305-10.2010}} @article{Chaigneau:2007, Abstract = {In the brain, neuronal activation triggers an increase in cerebral blood flow (CBF). Here, we use two animal models and several techniques (two-photon imaging of CBF and neuronal calcium dynamics, intracellular and extracellular recordings, local pharmacology) to analyze the relationship between neuronal activity and local CBF during odor stimulation in the rodent olfactory bulb. Application of glutamate receptor antagonists or tetrodotoxin directly into single rat olfactory glomeruli blocked postsynaptic responses but did not affect the local odor-evoked CBF increases. This suggests that in our experimental conditions, odor always activates more than one glomerulus and that silencing one of a few clustered glomeruli does not affect the vascular response. To block synaptic transmission more widely, we then superfused glutamate antagonists over the surface of the olfactory bulb in transgenic G-CaMP2 mice. This was for two reasons: (1) mice have a thin olfactory nerve layer compared to rats and this will favor drug access to the glomerular layer, and (2) transgenic G-CaMP2 mice express the fluorescent calcium sensor protein G-CaMP2 in mitral cells. In G-CaMP2 mice, odor-evoked, odor-specific, and concentration-dependent calcium increases in glomeruli. Superfusion of glutamate receptor antagonists blocked odor-evoked postsynaptic calcium signals and CBF responses. We conclude that activation of postsynaptic glutamate receptors and rises in dendritic calcium are major steps for neurovascular coupling in olfactory bulb glomeruli.}, Author = {Chaigneau, Emmanuelle and Tiret, Pascale and Lecoq, J{\'e}r{\^o}me and Ducros, Mathieu and Kn{\"o}pfel, Thomas and Charpak, Serge}, Date-Added = {2011-03-07 14:50:25 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Circuit structure-function;21 Neurophysiology;Olfactory Bulb;in vivo;function;imaging;microscopy;calcium imaging;optical imaging;frontiers review}, Mesh = {2-Amino-5-phosphonovalerate; Age Factors; Animals; Animals, Newborn; Benzaldehydes; Blood Circulation Time; Calcium; Cerebrovascular Circulation; Excitatory Amino Acid Antagonists; Glomerular Mesangium; Long-Term Potentiation; Mice; Mice, Transgenic; Microscopy, Confocal; Neurons; Odors; Olfactory Bulb; Patch-Clamp Techniques; Quinoxalines; Rats; Rats, Wistar; Tetrodotoxin}, Month = {Jun}, Number = {24}, Pages = {6452-60}, pmid = {17567806}, Pst = {ppublish}, Title = {The relationship between blood flow and neuronal activity in the rodent olfactory bulb}, Volume = {27}, Year = {2007}, url = {papers/Chaigneau_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3141-06.2007}} @article{Lecoq:2009, Abstract = {Adaptation is a general property of sensory receptor neurons and has been extensively studied in isolated cell preparation of olfactory receptor neurons. In contrast, little is known about the conditions under which peripheral adaptation occurs in the CNS during odorant stimulation. Here, we used two-photon laser-scanning microscopy and targeted extracellular recording in freely breathing anesthetized rats to investigate the correlate of peripheral adaptation at the first synapse of the olfactory pathway in olfactory bulb glomeruli. We find that during sustained stimulation at high concentration, odorants can evoke local field potential (LFP) postsynaptic responses that rapidly adapt with time, some within two inhalations. Simultaneous measurements of LFP and calcium influx at olfactory receptor neuron terminals reveal that postsynaptic adaptation is associated with a decrease in odorant-evoked calcium response, suggesting that it results from a decrease in glutamate release. This glomerular adaptation was concentration-dependent and did not change the glomerular input-output curve. In addition, in situ application of antagonists of either ionotropic glutamate receptors or metabotropic GABA(B) receptors did not affect this adaptation, thus discarding the involvement of local presynaptic inhibition. Glomerular adaptation, therefore, reflects the response decline of olfactory receptor neurons to sustained odorant. We postulate that peripheral fast adaptation is a means by which glomerular output codes for high concentration of odor.}, Author = {Lecoq, J{\'e}r{\^o}me and Tiret, Pascale and Charpak, Serge}, Date-Added = {2011-03-07 14:50:25 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Circuit structure-function;21 Neurophysiology;Olfactory Bulb;in vivo;function;imaging;microscopy;calcium imaging;optical imaging}, Mesh = {Adaptation, Physiological; Animals; Odors; Olfactory Bulb; Olfactory Pathways; Peripheral Nerves; Rats; Rats, Wistar; Smell}, Month = {Mar}, Number = {10}, Pages = {3067-72}, pmid = {19279243}, Pst = {ppublish}, Title = {Peripheral adaptation codes for high odor concentration in glomeruli}, Volume = {29}, Year = {2009}, url = {papers/Lecoq_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.6187-08.2009}} @article{Cline:2008, Abstract = {The synaptotropic hypothesis, which states that synaptic inputs control the elaboration of dendritic (and axonal) arbors was articulated by Vaughn in 1989. Today the role of synaptic inputs in controlling neuronal structural development remains an area of intense research activity. Several recent studies have applied modern molecular genetic, imaging and electrophysiological methods to this question and now provide strong evidence that maturation of excitatory synaptic inputs is required for the development of neuronal structure in the intact brain. Here we critically review data concerning the hypothesis with the expectation that understanding the circumstances when the data do and do not support the hypothesis will be most valuable. The synaptotrophic hypothesis contributes at both conceptual and mechanistic levels to our understanding of how relatively minor changes in levels or function of synaptic proteins may have profound effects on circuit development and plasticity.}, Author = {Cline, Hollis and Haas, Kurt}, Date-Added = {2011-03-07 14:47:02 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {21 Activity-development;Synapses;pruning;structural remodeling;visual system;development;plasticity;Critical Period}, Mesh = {Aging; Animals; Axons; Dendrites; Glutamic Acid; Humans; Models, Neurological; Neuronal Plasticity; Receptors, Glutamate; Synapses; Synaptic Transmission}, Month = {Mar}, Number = {6}, Pages = {1509-17}, Pmc = {PMC2375708}, pmid = {18202093}, Pst = {ppublish}, Title = {The regulation of dendritic arbor development and plasticity by glutamatergic synaptic input: a review of the synaptotrophic hypothesis}, Volume = {586}, Year = {2008}, url = {papers/Cline_JPhysiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2007.150029}} @article{Dombeck:2009, Abstract = {Macroscopic (millimeter scale) functional clustering is a hallmark characteristic of motor cortex spatial organization in awake behaving mammals; however, almost no information is known about the functional micro-organization (approximately 100 microm scale). Here, we optically recorded intracellular calcium transients of layer 2/3 neurons with cellular resolution over approximately 200-microm-diameter fields in the forelimb motor cortex of mobile, head-restrained mice during two distinct movements (running and grooming). We showed that the temporal correlation between neurons was statistically larger the closer the neurons were to each other. We further explored this correlation by using two separate methods to spatially segment the neurons within each imaging field: K-means clustering and correlations between single neuron activity and mouse movements. The two methods segmented the neurons similarly and led to the conclusion that the origin of the inverse relationship between correlation and distance seen statistically was twofold: clusters of highly temporally correlated neurons were often spatially distinct from one another, and (even when the clusters were spatially intermingled) within the clusters, the more correlated the neurons were to each other, the shorter the distance between them. Our results represent a direct observation of functional clustering within the microcircuitry of the awake mouse motor cortex.}, Author = {Dombeck, Daniel A and Graziano, Michael S and Tank, David W}, Date-Added = {2011-03-07 14:43:54 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Calcium imaging;calcium imaging;optical imaging;imaging;Multiphoton;microscopy;in vivo;21 Circuit structure-function;Motor Activity;Motor Cortex;21 Neurophysiology;frontiers review}, Mesh = {Animals; Cluster Analysis; Diagnostic Imaging; Image Processing, Computer-Assisted; Male; Mice; Mice, Inbred CBA; Microscopy, Fluorescence, Multiphoton; Motor Activity; Motor Cortex; Neurons; Wakefulness}, Month = {Nov}, Number = {44}, Pages = {13751-60}, Pmc = {PMC2872549}, pmid = {19889987}, Pst = {ppublish}, Title = {Functional clustering of neurons in motor cortex determined by cellular resolution imaging in awake behaving mice}, Volume = {29}, Year = {2009}, url = {papers/Dombeck_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2985-09.2009}} @article{Kim:2009, Abstract = {Tools for suppressing synaptic transmission gain power when able to target highly selective neuron subtypes, thereby sharpening attainable links between neuron type, behavior, and disease; and when able to silence most any neuron subtype, thereby offering broad applicability. Here, we present such a tool, RC::PFtox, that harnesses breadth in scope along with high cell-type selection via combinatorial gene expression to deliver tetanus toxin light chain (tox), an inhibitor of vesicular neurotransmission. When applied in mice, we observed cell-type-specific disruption of vesicle exocytosis accompanied by loss of excitatory postsynaptic currents and commensurately perturbed behaviors. Among various test populations, we applied RC::PFtox to silence serotonergic neurons, en masse or a subset defined combinatorially. Of the behavioral phenotypes observed upon en masse serotonergic silencing, only one mapped to the combinatorially defined subset. These findings provide evidence for separability by genetic lineage of serotonin-modulated behaviors; collectively, these findings demonstrate broad utility of RC::PFtox for dissecting neuron functions.}, Author = {Kim, Jun Chul and Cook, Melloni N and Carey, Megan R and Shen, Chung and Regehr, Wade G and Dymecki, Susan M}, Date-Added = {2011-03-07 14:41:58 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Genetic Engineering;optogenetics;frontiers review;mouse;21 Activity-development;activity manipulation;review;23 Technique}, Mesh = {Acoustic Stimulation; Analysis of Variance; Animals; Animals, Newborn; Basic Helix-Loop-Helix Transcription Factors; Behavior, Animal; Biophysics; Cerebellum; Conditioning (Psychology); Electric Stimulation; Exploratory Behavior; Fear; GABA Antagonists; Genetic Linkage; Green Fluorescent Proteins; Maze Learning; Mice; Mice, Transgenic; Microscopy, Electron, Transmission; Models, Neurological; Nerve Tissue Proteins; Neurons; Patch-Clamp Techniques; Phenotype; Phosphinic Acids; Propanolamines; Proteins; Recombinases; Serotonin; Startle Reaction; Synaptic Transmission; Tetanus Toxin; Vesicle-Associated Membrane Protein 2}, Month = {Aug}, Number = {3}, Pages = {305-15}, Pmc = {PMC2814245}, pmid = {19679071}, Pst = {ppublish}, Title = {Linking genetically defined neurons to behavior through a broadly applicable silencing allele}, Volume = {63}, Year = {2009}, url = {papers/Kim_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.07.010}} @article{Triplett:2009, Abstract = {Sensory information is represented in the brain in the form of topographic maps, in which neighboring neurons respond to adjacent external stimuli. In the visual system, the superior colliculus receives topographic projections from the retina and primary visual cortex (V1) that are aligned. Alignment may be achieved through the use of a gradient of shared axon guidance molecules, or through a retinal-matching mechanism in which axons that monitor identical regions of visual space align. To distinguish between these possibilities, we take advantage of genetically engineered mice that we show have a duplicated functional retinocollicular map but only a single map in V1. Anatomical tracing revealed that the corticocollicular projection bifurcates to align with the duplicated retinocollicular map in a manner dependent on the normal pattern of spontaneous activity during development. These data suggest a general model in which convergent maps use coincident activity patterns to achieve alignment.}, Author = {Triplett, Jason W and Owens, Melinda T and Yamada, Jena and Lemke, Greg and Cang, Jianhua and Stryker, Michael P and Feldheim, David A}, Date-Added = {2011-03-07 14:39:33 -0500}, Date-Modified = {2013-05-21 20:36:03 +0000}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {21 Activity-development;Spontaneous activity;retina;Superior Colliculus;optic tectum;visual cortex;development;retinal wave paper; currOpinRvw}, Mesh = {Animals; Brain Mapping; Gene Knock-In Techniques; Homeodomain Proteins; Mice; Neurogenesis; Ocular Physiological Phenomena; Receptor, EphA3; Retina; Superior Colliculi; Visual Cortex; Visual Pathways}, Month = {Oct}, Number = {1}, Pages = {175-85}, Pmc = {PMC2814139}, pmid = {19804762}, Pst = {ppublish}, Title = {Retinal input instructs alignment of visual topographic maps}, Volume = {139}, Year = {2009}, url = {papers/Triplett_Cell2009.pdf}, Bdsk-File-2 = {papers/Triplett_Cell2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2009.08.028}} @article{Fuentes-Medel:2009, Abstract = {Synapse remodeling is an extremely dynamic process, often regulated by neural activity. Here we show during activity-dependent synaptic growth at the Drosophila NMJ many immature synaptic boutons fail to form stable postsynaptic contacts, are selectively shed from the parent arbor, and degenerate or disappear from the neuromuscular junction (NMJ). Surprisingly, we also observe the widespread appearance of presynaptically derived "debris" during normal synaptic growth. The shedding of both immature boutons and presynaptic debris is enhanced by high-frequency stimulation of motorneurons, indicating that their formation is modulated by neural activity. Interestingly, we find that glia dynamically invade the NMJ and, working together with muscle cells, phagocytose shed presynaptic material. Suppressing engulfment activity in glia or muscle by disrupting the Draper/Ced-6 pathway results in a dramatic accumulation of presynaptic debris, and synaptic growth in turn is severely compromised. Thus actively growing NMJ arbors appear to constitutively generate an excessive number of immature boutons, eliminate those that are not stabilized through a shedding process, and normal synaptic expansion requires the continuous clearance of this material by both glia and muscle cells.}, Author = {Fuentes-Medel, Yuly and Logan, Mary A and Ashley, James and Ataman, Bulent and Budnik, Vivian and Freeman, Marc R}, Date-Added = {2011-03-07 14:35:25 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {pruning;microglia;macrophage;glia;Synapses;development;21 Activity-development;Imaging;structural remodeling;cell interaction;axon guidance;Axons}, Mesh = {Animals; Drosophila; Drosophila Proteins; Larva; Membrane Proteins; Microscopy, Confocal; Muscles; Neuroglia; Neuromuscular Junction; Presynaptic Terminals; Reverse Transcriptase Polymerase Chain Reaction; Synapses; Synaptic Transmission}, Month = {Aug}, Number = {8}, Pages = {e1000184}, Pmc = {PMC2724735}, pmid = {19707574}, Pst = {ppublish}, Title = {Glia and muscle sculpt neuromuscular arbors by engulfing destabilized synaptic boutons and shed presynaptic debris}, Volume = {7}, Year = {2009}, url = {papers/Fuentes-Medel_PLoSBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1000184}} @article{Fuerst:2009, Abstract = {DSCAM and DSCAM-LIKE1 (DSCAML1) serve diverse neurodevelopmental functions, including axon guidance, synaptic adhesion, and self-avoidance, depending on the species, cell type, and gene family member studied. We examined the function of DSCAM and DSCAML1 in the developing mouse retina. In addition to a subset of amacrine cells, Dscam was expressed in most retinal ganglion cells (RGCs). RGCs had fasciculated dendrites and clumped cell bodies in Dscam(-/-) mice, suggesting a role in self-avoidance. Dscaml1 was expressed in the rod circuit, and mice lacking Dscaml1 had fasciculated rod bipolar cell dendrites and clumped AII amacrine cell bodies, also indicating a role in self-avoidance. Neurons in Dscam or Dscaml1 mutant retinas stratified their processes appropriately in synaptic laminae in the inner plexiform layer, and functional synapses formed in the rod circuit in mice lacking Dscaml1. Therefore, DSCAM and DSCAML1 function similarly in self-avoidance, and are not essential for synaptic specificity in the mouse retina.}, Author = {Fuerst, Peter G and Bruce, Freyja and Tian, Miao and Wei, Wei and Elstrott, Justin and Feller, Marla B and Erskine, Lynda and Singer, Joshua H and Burgess, Robert W}, Date-Added = {2011-03-07 14:33:23 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {cell interaction;Cell Adhesion;retina;development;cell migration;Cell Migration Inhibition;self organization;visual system}, Mesh = {Animals; Avoidance Learning; Cell Adhesion Molecules; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Neurites; Retina; Synapses}, Month = {Nov}, Number = {4}, Pages = {484-97}, Pmc = {PMC2850049}, pmid = {19945391}, Pst = {ppublish}, Title = {DSCAM and DSCAML1 function in self-avoidance in multiple cell types in the developing mouse retina}, Volume = {64}, Year = {2009}, url = {papers/Fuerst_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.09.027}} @article{Dunfield:2009, Abstract = {During embryogenesis, brain neurons receiving the same sensory input may undergo potentiation or depression. While the origin of variable plasticity in vivo is unknown, it plays a key role in shaping dynamic neural circuit refinement. Here, we investigate effects of natural visual stimuli on neuronal firing within the intact, awake, developing brain using calcium imaging of 100 s of central neurons in the Xenopus retinotectal system. We find that specific patterns of visual stimuli shift population responses toward either potentiation or depression in an N-methyl-D-aspartate receptor (NMDA-R)-dependent manner. In agreement with Bienenstock-Cooper-Munro metaplasticity, our results show that functional potentiation or depression can be predicted by individual neurons' specific receptive field properties and historic firing rates. Interestingly, this activity-dependent metaplasticity is itself NMDA-R dependent. Furthermore, network analysis reveals increased correlated firing of neurons that undergo potentiation. These findings implicate metaplasticity as a natural property regulating experience-dependent refinement of nascent embryonic brain circuits.}, Author = {Dunfield, Derek and Haas, Kurt}, Date-Added = {2011-03-07 14:31:17 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;experience dependent plasticity;plasticity;hebbian;frontiers review;imaging;in vivo;optical imaging;calcium imaging;}, Mesh = {2-Amino-5-phosphonovalerate; Action Potentials; Animals; Behavior, Animal; Biophysics; Brain; Calcium; Electric Stimulation; Excitatory Amino Acid Antagonists; Long-Term Potentiation; Models, Neurological; Nerve Net; Neurons; Photic Stimulation; Statistics as Topic; Superior Colliculi; Synapses; Visual Pathways; Xenopus laevis}, Month = {Oct}, Number = {2}, Pages = {240-50}, pmid = {19874791}, Pst = {ppublish}, Title = {Metaplasticity governs natural experience-driven plasticity of nascent embryonic brain circuits}, Volume = {64}, Year = {2009}, url = {papers/Dunfield_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.08.034}} @article{Helmchen:2001, Abstract = {Two-photon microscopy has enabled anatomical and functional fluorescence imaging in the intact brain of rats. Here, we extend two-photon imaging from anesthetized, head-stabilized to awake, freely moving animals by using a miniaturized head-mounted microscope. Excitation light is conducted to the microscope in a single-mode optical fiber, and images are scanned using vibrations of the fiber tip. Microscope performance was first characterized in the neocortex of anesthetized rats. We readily obtained images of vasculature filled with fluorescently labeled blood and of layer 2/3 pyramidal neurons filled with a calcium indicator. Capillary blood flow and dendritic calcium transients were measured with high time resolution using line scans. In awake, freely moving rats, stable imaging was possible except during sudden head movements.}, Author = {Helmchen, F and Fee, M S and Tank, D W and Denk, W}, Date-Added = {2011-03-07 14:27:33 -0500}, Date-Modified = {2011-03-07 14:28:34 -0500}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {23 Technique;Imaging;Multiphoton;calcium imaging;Optics;in vivo;microscopy}, Mesh = {Anesthesia; Animals; Artifacts; Brain; Calcium Signaling; Cerebrovascular Circulation; Dendrites; Dextrans; Equipment Design; Fiber Optic Technology; Fluorescein-5-isothiocyanate; Fluorescent Dyes; Head Movements; Image Processing, Computer-Assisted; Lasers; Microcirculation; Microscopy, Fluorescence; Miniaturization; Movement; Optical Fibers; Organic Chemicals; Pyramidal Cells; Rats; Rats, Sprague-Dawley; Wakefulness}, Month = {Sep}, Number = {6}, Pages = {903-12}, pmid = {11580892}, Pst = {ppublish}, Title = {A miniature head-mounted two-photon microscope. high-resolution brain imaging in freely moving animals}, Volume = {31}, Year = {2001}, url = {papers/Helmchen_Neuron2001.pdf}} @article{Lim:1997a, Abstract = {Optic nerve-evoked responses were measured in the superior colliculus (SC) of neonatal rats in vivo from postnatal day (P) 0 to P11. At P1, a biphasic response was recorded in superficial layers and the amplitude diminished as the electrode penetrated into the deeper layers of the SC. By P2, a similar response, with a fast positive-going potential followed by a more prolonged negative potential was observed at the surface. The polarity of the response reversed as the electrode was moved into the deeper laminae of the SC. Such a reversal in the polarity of optic nerve-evoked responses resembled those observed in more mature preparations. Using current source density analysis, a single pair of source-sink could be identified following optic nerve stimulation at P2, and this changed to a more complex pattern by P11. Our results suggest that synaptic transmission in the retinocollicular pathway of the rat is functional as early as P2.}, Author = {Lim, C H and Ho, S M}, Date-Added = {2011-03-07 14:25:08 -0500}, Date-Modified = {2011-03-07 14:26:28 -0500}, Journal = {Neurosci Lett}, Journal-Full = {Neuroscience letters}, Keywords = {development;retina;Superior Colliculus;optic tectum;21 Neurophysiology;Synapses;connectivity;21 Activity-development;function;visual system}, Mesh = {Animals; Animals, Newborn; Electric Stimulation; Excitatory Postsynaptic Potentials; Optic Nerve; Rats; Rats, Wistar; Superior Colliculi}, Month = {Oct}, Number = {3}, Pages = {141-4}, pmid = {9406889}, Pst = {ppublish}, Title = {Early detection of optic nerve-evoked response in the superior colliculus of the neonatal rat}, Volume = {235}, Year = {1997}, url = {papers/Lim_NeurosciLett1997.pdf}} @article{Takahashi:2009, Abstract = {As an experimental model to study the mechanism of large-scale network plasticity of the juvenile brain, functional compensation after neonatal brain damage was studied in rats that received unilateral decortication at postnatal day 5. These animals exhibited a marked ability in reaching and grasping movements in the contralesional side of the forelimb when tested at 10-14 weeks of age. Additional lesion of the sensorimotor cortex in the remaining contralesional hemisphere at this stage resulted in severe impairment of both forelimbs. It was suggested that the sensorimotor cortex on the contralesional side was controlling the movements of both forelimbs. Following the injection of an anterograde tracer into the remaining sensorimotor cortex, the corticofugal axons from the remaining sensorimotor cortex were found to issue aberrant projections to the contralateral red nucleus, contralateral superior colliculus, contralateral pontine nuclei, ipsilateral dorsal column nucleus and ipsilateral gray matter of the cervical spinal cord, all of which appeared to be necessary for the control of contralesional forelimb movements. These results suggest that the forelimb movements on the contralesional side were compensated by large-scale reorganization of the corticofugal axons from the remaining sensorimotor cortex.}, Author = {Takahashi, Masahito and Vattanajun, Anusara and Umeda, Tatsuya and Isa, Kaoru and Isa, Tadashi}, Date-Added = {2011-03-07 14:22:26 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {Superior Colliculus;optic tectum;structural remodeling;development;plasticity;visual system;visual cortex;multisensory integration;Critical Period;function;self organization}, Mesh = {Afferent Pathways; Animals; Animals, Newborn; Biotin; Brain Stem; Cerebral Cortex; Cerebral Decortication; Dextrans; Forelimb; Functional Laterality; Movement; Neuronal Plasticity; Psychomotor Performance; Rats; Rats, Wistar; Recovery of Function; Video Recording}, Month = {Nov}, Number = {10}, Pages = {1878-87}, pmid = {19895560}, Pst = {ppublish}, Title = {Large-scale reorganization of corticofugal fibers after neonatal hemidecortication for functional restoration of forelimb movements}, Volume = {30}, Year = {2009}, url = {papers/Takahashi_EurJNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2009.06989.x}} @article{Isa:2009, Abstract = {The superior colliculus plays an important role in the translation of sensory signals that encode the location of objects in space into motor signals that encode vectors of the shifts in gaze direction called saccades. Since the late 1990s, our two laboratories have been applying whole cell patch-clamp techniques to in vitro slice preparations of rodent superior colliculus to analyze the structure and function of its circuitry at the cellular level. This review describes the results of these experiments and discusses their contributions to our understanding of the mechanisms responsible for sensorimotor integration in the superior colliculus. The experiments analyze vertical interactions between its superficial visuosensory and intermediate premotor layers and propose how they might contribute to express saccades and to saccadic suppression. They also compare and contrast the circuitry within each of these layers and propose how this circuitry might contribute to the selection of the targets for saccades and to the build-up of the premotor commands that precede saccades. Experiments also explore in vitro the roles of extrinsic inputs to the superior colliculus, including cholinergic inputs from the parabigeminal and parabrachial nuclei and GABAergic inputs from the substantia nigra pars reticulata, in modulating the activity of the collicular circuitry. The results extend and clarify our understanding of the multiple roles the superior colliculus plays in sensorimotor integration.}, Author = {Isa, Tadashi and Hall, William C}, Date-Added = {2011-03-07 14:20:20 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {Superior Colliculus;optic tectum;in vitro;21 Circuit structure-function;21 Neurophysiology;GABA;Circuits;function;visual system}, Mesh = {Action Potentials; Animals; Computer Simulation; Models, Neurological; Nerve Net; Neural Inhibition; Neural Pathways; Neurons; Saccades; Superior Colliculi; gamma-Aminobutyric Acid}, Month = {Nov}, Number = {5}, Pages = {2581-93}, Pmc = {PMC2777828}, pmid = {19710376}, Pst = {ppublish}, Title = {Exploring the superior colliculus in vitro}, Volume = {102}, Year = {2009}, url = {papers/Isa_JNeurophysiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00498.2009}} @article{Jacobs:1991, Abstract = {High sensitivity to near-ultraviolet light is a fundamental feature of vision in many invertebrates. Among vertebrates there are some amphibians, birds and fishes that are also sensitive to near-ultraviolet wavelengths. This sensitivity can be achieved through a class of cone photoreceptor containing an ultraviolet-sensitive pigment. Although these receptors were thought not to exist in the eyes of mammals, we now report that some rodents have a retinal mechanism that is maximally sensitive to ultraviolet light.}, Author = {Jacobs, G H and Neitz, J and Deegan, 2nd, J F}, Date-Added = {2011-03-07 14:18:03 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {retina;function;Photoreceptors;optic tectum;Superior Colliculus;visual system;Color Perception;mouse}, Mesh = {Animals; Electrophysiology; Electroretinography; Gerbillinae; Mice; Photic Stimulation; Photoreceptor Cells; Rats; Retina; Rodentia; Ultraviolet Rays}, Month = {Oct}, Number = {6345}, Pages = {655-6}, pmid = {1922382}, Pst = {ppublish}, Title = {Retinal receptors in rodents maximally sensitive to ultraviolet light}, Volume = {353}, Year = {1991}, url = {papers/Jacobs_Nature1991.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/353655a0}} @article{Chung:2009, Abstract = {A primer on new research by Fuentes-Medel and colleagues explains the important role of non-neural cells in clearing neural debris, which is continuously produced during the normal remodeling processes that establish and maintain neural connectivity.}, Author = {Chung, Won-Suk and Barres, Ben A}, Date-Added = {2011-03-07 14:13:28 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {21 Activity-development;axon guidance;pruning;refinement;connectivity;review;visual system;development;plasticity;structural remodeling;Cooperative Behavior;Competitive Behavior}, Mesh = {Animals; Drosophila; Drosophila Proteins; Larva; Membrane Proteins; Microscopy, Confocal; Muscles; Neuroglia; Neuromuscular Junction; Presynaptic Terminals; Reverse Transcriptase Polymerase Chain Reaction; Synapses; Synaptic Transmission}, Month = {Aug}, Number = {8}, Pages = {e1000185}, Pmc = {PMC2722723}, pmid = {19707269}, Pst = {ppublish}, Title = {Selective remodeling: refining neural connectivity at the neuromuscular junction}, Volume = {7}, Year = {2009}, url = {papers/Chung_PLoSBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1000185}} @article{Tremblay:2010, Abstract = {Microglia are the immune cells of the brain. In the absence of pathological insult, their highly motile processes continually survey the brain parenchyma and transiently contact synaptic elements. Aside from monitoring, their physiological roles at synapses are not known. To gain insight into possible roles of microglia in the modification of synaptic structures, we used immunocytochemical electron microscopy, serial section electron microscopy with three-dimensional reconstructions, and two-photon in vivo imaging to characterize microglial interactions with synapses during normal and altered sensory experience, in the visual cortex of juvenile mice. During normal visual experience, most microglial processes displayed direct apposition with multiple synapse-associated elements, including synaptic clefts. Microglial processes were also distinctively surrounded by pockets of extracellular space. In terms of dynamics, microglial processes localized to the vicinity of small and transiently growing dendritic spines, which were typically lost over 2 d. When experience was manipulated through light deprivation and reexposure, microglial processes changed their morphology, showed altered distributions of extracellular space, displayed phagocytic structures, apposed synaptic clefts more frequently, and enveloped synapse-associated elements more extensively. While light deprivation induced microglia to become less motile and changed their preference of localization to the vicinity of a subset of larger dendritic spines that persistently shrank, light reexposure reversed these behaviors. Taken together, these findings reveal different modalities of microglial interactions with synapses that are subtly altered by sensory experience. These findings suggest that microglia may actively contribute to the experience-dependent modification or elimination of a specific subset of synapses in the healthy brain.}, Author = {Tremblay, Marie-{\`E}ve and Lowery, Rebecca L and Majewska, Ania K}, Date-Added = {2011-03-07 14:11:06 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {21 Activity-development;visual cortex;visual system;microglia;macrophage;Immune System;Imaging;Multiphoton;microscopy;in vivo;Synapses;cell interaction}, Mesh = {Animals; Extracellular Space; Mice; Microglia; Microscopy, Electron; Synapses; Vision, Ocular}, Number = {11}, Pages = {e1000527}, Pmc = {PMC2970556}, pmid = {21072242}, Pst = {epublish}, Title = {Microglial interactions with synapses are modulated by visual experience}, Volume = {8}, Year = {2010}, url = {papers/Tremblay_PLoSBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1000527}} @article{Godfrey:2009, Abstract = {During development, neurons extend axons to different brain areas and produce stereotypical patterns of connections. The mechanisms underlying this process have been intensively studied in the visual system, where retinal neurons form retinotopic maps in the thalamus and superior colliculus. The mechanisms active in map formation include molecular guidance cues, trophic factor release, spontaneous neural activity, spike-timing dependent plasticity (STDP), synapse creation and retraction, and axon growth, branching and retraction. To investigate how these mechanisms interact, a multi-component model of the developing retinocollicular pathway was produced based on phenomenological approximations of each of these mechanisms. Core assumptions of the model were that the probabilities of axonal branching and synaptic growth are highest where the combined influences of chemoaffinity and trophic factor cues are highest, and that activity-dependent release of trophic factors acts to stabilize synapses. Based on these behaviors, model axons produced morphologically realistic growth patterns and projected to retinotopically correct locations in the colliculus. Findings of the model include that STDP, gradient detection by axonal growth cones and lateral connectivity among collicular neurons were not necessary for refinement, and that the instructive cues for axonal growth appear to be mediated first by molecular guidance and then by neural activity. Although complex, the model appears to be insensitive to variations in how the component developmental mechanisms are implemented. Activity, molecular guidance and the growth and retraction of axons and synapses are common features of neural development, and the findings of this study may have relevance beyond organization in the retinocollicular pathway.}, Author = {Godfrey, Keith B and Eglen, Stephen J and Swindale, Nicholas V}, Date-Added = {2011-03-07 14:09:21 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {21 Activity-development;Retina;LGN;development;Computational Biology;Theoretical;Models;plasticity;hebbian;retinal wave paper;axon guidance;Axons;optic tectum;Superior Colliculus}, Mesh = {Animals; Axons; Behavior, Animal; Mice; Models, Neurological; Probability; Retina; Synapses; Vision, Ocular}, Month = {Dec}, Number = {12}, Pages = {e1000600}, Pmc = {PMC2782179}, pmid = {20011124}, Pst = {ppublish}, Title = {A multi-component model of the developing retinocollicular pathway incorporating axonal and synaptic growth}, Volume = {5}, Year = {2009}, url = {papers/Godfrey_PLoSComputBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.1000600}} @article{Gjorgjieva:2009, Abstract = {Spontaneous retinal activity (known as "waves") remodels synaptic connectivity to the lateral geniculate nucleus (LGN) during development. Analysis of retinal waves recorded with multielectrode arrays in mouse suggested that a cue for the segregation of functionally distinct (ON and OFF) retinal ganglion cells (RGCs) in the LGN may be a desynchronization in their firing, where ON cells precede OFF cells by one second. Using the recorded retinal waves as input, with two different modeling approaches we explore timing-based plasticity rules for the evolution of synaptic weights to identify key features underlying ON/OFF segregation. First, we analytically derive a linear model for the evolution of ON and OFF weights, to understand how synaptic plasticity rules extract input firing properties to guide segregation. Second, we simulate postsynaptic activity with a nonlinear integrate-and-fire model to compare findings with the linear model. We find that spike-time-dependent plasticity, which modifies synaptic weights based on millisecond-long timing and order of pre- and postsynaptic spikes, fails to segregate ON and OFF retinal inputs in the absence of normalization. Implementing homeostatic mechanisms results in segregation, but only with carefully-tuned parameters. Furthermore, extending spike integration timescales to match the second-long input correlation timescales always leads to ON segregation because ON cells fire before OFF cells. We show that burst-time-dependent plasticity can robustly guide ON/OFF segregation in the LGN without normalization, by integrating pre- and postsynaptic bursts irrespective of their firing order and over second-long timescales. We predict that an LGN neuron will become ON- or OFF-responsive based on a local competition of the firing patterns of neighboring RGCs connecting to it. Finally, we demonstrate consistency with ON/OFF segregation in ferret, despite differences in the firing properties of retinal waves. Our model suggests that diverse input statistics of retinal waves can be robustly interpreted by a burst-based rule, which underlies retinogeniculate plasticity across different species.}, Author = {Gjorgjieva, Julijana and Toyoizumi, Taro and Eglen, Stephen J}, Date-Added = {2011-03-07 14:07:38 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {21 Activity-development;Retina;LGN;development;Computational Biology;Theoretical;Models;plasticity;hebbian;retinal wave paper}, Mesh = {Action Potentials; Animals; Computer Simulation; Geniculate Bodies; Mice; Models, Neurological; Nerve Net; Neural Inhibition; Neuronal Plasticity; Retinal Ganglion Cells; Visual Perception}, Month = {Dec}, Number = {12}, Pages = {e1000618}, Pmc = {PMC2790088}, pmid = {20041207}, Pst = {ppublish}, Title = {Burst-time-dependent plasticity robustly guides ON/OFF segregation in the lateral geniculate nucleus}, Volume = {5}, Year = {2009}, url = {papers/Gjorgjieva_PLoSComputBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.1000618}} @article{Betley:2009, Abstract = {GABAergic interneurons are key elements in neural coding, but the mechanisms that assemble inhibitory circuits remain unclear. In the spinal cord, the transfer of sensory signals to motor neurons is filtered by GABAergic interneurons that act presynaptically to inhibit sensory transmitter release and postsynaptically to inhibit motor neuron excitability. We show here that the connectivity and synaptic differentiation of GABAergic interneurons that mediate presynaptic inhibition is directed by their sensory targets. In the absence of sensory terminals these GABAergic neurons shun other available targets, fail to undergo presynaptic differentiation, and withdraw axons from the ventral spinal cord. A sensory-specific source of brain derived neurotrophic factor induces synaptic expression of the GABA synthetic enzyme GAD65--a defining biochemical feature of this set of interneurons. The organization of a GABAergic circuit that mediates presynaptic inhibition in the mammalian CNS is therefore controlled by a stringent program of sensory recognition and signaling.}, Author = {Betley, J Nicholas and Wright, Christopher V E and Kawaguchi, Yoshiya and Erd{\'e}lyi, Ferenc and Szab{\'o}, G{\'a}bor and Jessell, Thomas M and Kaltschmidt, Julia A}, Date-Added = {2011-03-07 13:44:57 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {21 Activity-development;Interneurons;GABA;10 circuit formation;Axons;cell interaction;Spinal Cord;frontiers review;structural remodeling;plasticity;Sensory Deprivation;experience dependent plasticity}, Mesh = {Animals; Brain-Derived Neurotrophic Factor; Glutamate Decarboxylase; Interneurons; Mice; Motor Neurons; Presynaptic Terminals; Proprioception; Sensory Receptor Cells; Spinal Cord; gamma-Aminobutyric Acid}, Month = {Oct}, Number = {1}, Pages = {161-74}, Pmc = {PMC2812434}, pmid = {19804761}, Pst = {ppublish}, Title = {Stringent specificity in the construction of a GABAergic presynaptic inhibitory circuit}, Volume = {139}, Year = {2009}, url = {papers/Betley_Cell2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2009.08.027}} @article{Kerschensteiner:2009, Abstract = {Activity is thought to guide the patterning of synaptic connections in the developing nervous system. Specifically, differences in the activity of converging inputs are thought to cause the elimination of synapses from less active inputs and increase connectivity with more active inputs. Here we present findings that challenge the generality of this notion and offer a new view of the role of activity in synapse development. To imbalance neurotransmission from different sets of inputs in vivo, we generated transgenic mice in which ON but not OFF types of bipolar cells in the retina express tetanus toxin (TeNT). During development, retinal ganglion cells (RGCs) select between ON and OFF bipolar cell inputs (ON or OFF RGCs) or establish a similar number of synapses with both on separate dendritic arborizations (ON-OFF RGCs). In TeNT retinas, ON RGCs correctly selected the silenced ON bipolar cell inputs over the transmitting OFF bipolar cells, but were connected with them through fewer synapses at maturity. Time-lapse imaging revealed that this was caused by a reduced rate of synapse formation rather than an increase in synapse elimination. Similarly, TeNT-expressing ON bipolar cell axons generated fewer presynaptic active zones. The remaining active zones often recruited multiple, instead of single, synaptic ribbons. ON-OFF RGCs in TeNT mice maintained convergence of ON and OFF bipolar cells inputs and had fewer synapses on their ON arbor without changes to OFF arbor synapses. Our results reveal an unexpected and remarkably selective role for activity in circuit development in vivo, regulating synapse formation but not elimination, affecting synapse number but not dendritic or axonal patterning, and mediating independently the refinement of connections from parallel (ON and OFF) processing streams even where they converge onto the same postsynaptic cell.}, Author = {Kerschensteiner, Daniel and Morgan, Josh L and Parker, Edward D and Lewis, Renate M and Wong, Rachel O L}, Date-Added = {2011-03-07 13:41:50 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Activity-development;Synapses;23 Technique;frontiers review;in vitro;retina;development;10 circuit formation;Spontaneous activity;retinal wave paper;activity manipulation}, Mesh = {Animals; Axons; Dendrites; Female; Glutamic Acid; Male; Mice; Mice, Transgenic; Receptors, Kainic Acid; Retinal Bipolar Cells; Retinal Ganglion Cells; Synapses; Synaptic Transmission; Tetanus Toxin}, Month = {Aug}, Number = {7258}, Pages = {1016-20}, Pmc = {PMC2746695}, pmid = {19693082}, Pst = {ppublish}, Title = {Neurotransmission selectively regulates synapse formation in parallel circuits in vivo}, Volume = {460}, Year = {2009}, url = {papers/Kerschensteiner_Nature2009.pdf}, Bdsk-File-2 = {papers/Kerschensteiner_Nature2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08236}} @article{Lin:2010, Abstract = {New neurons are added to the adult brain throughout life, but only half ultimately integrate into existing circuits. Sensory experience is an important regulator of the selection of new neurons but it remains unknown whether experience provides specific patterns of synaptic input or simply a minimum level of overall membrane depolarization critical for integration. To investigate this issue, we genetically modified intrinsic electrical properties of adult-generated neurons in the mammalian olfactory bulb. First, we observed that suppressing levels of cell-intrinsic neuronal activity via expression of ESKir2.1 potassium channels decreases, whereas enhancing activity via expression of NaChBac sodium channels increases survival of new neurons. Neither of these modulations affects synaptic formation. Furthermore, even when neurons are induced to fire dramatically altered patterns of action potentials, increased levels of cell-intrinsic activity completely blocks cell death triggered by NMDA receptor deletion. These findings demonstrate that overall levels of cell-intrinsic activity govern survival of new neurons and precise firing patterns are not essential for neuronal integration into existing brain circuits.}, Author = {Lin, Chia-Wei and Sim, Shuyin and Ainsworth, Alice and Okada, Masayoshi and Kelsch, Wolfgang and Lois, Carlos}, Date-Added = {2011-03-07 13:35:25 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;01 Adult neurogenesis general;Dentate Gyrus;Hippocampus;Synapses;Genetic Engineering;frontiers review;repair;Regeneration;21 Neurophysiology}, Mesh = {Action Potentials; Animals; Cell Survival; Mice; Mice, Knockout; Nerve Net; Neurons; Olfactory Bulb; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying; Rats; Receptors, N-Methyl-D-Aspartate; Sodium Channels}, Month = {Jan}, Number = {1}, Pages = {32-9}, Pmc = {PMC2822732}, pmid = {20152111}, Pst = {ppublish}, Title = {Genetically increased cell-intrinsic excitability enhances neuronal integration into adult brain circuits}, Volume = {65}, Year = {2010}, url = {papers/Lin_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.12.001}} @article{Brown:2010, Abstract = {Photoreception in the mammalian retina is not restricted to rods and cones but extends to a subset of retinal ganglion cells expressing the photopigment melanopsin (mRGCs). These mRGCs are known to drive such reflex light responses as circadian photoentrainment and pupillomotor movements. By contrast, until now there has been no direct assessment of their contribution to conventional visual pathways. Here, we address this deficit. Using new reporter lines, we show that mRGC projections are much more extensive than previously thought and extend across the dorsal lateral geniculate nucleus (dLGN), origin of thalamo-cortical projection neurons. We continue to show that this input supports extensive physiological light responses in the dLGN and visual cortex in mice lacking rods+cones (a model of advanced retinal degeneration). Moreover, using chromatic stimuli to isolate melanopsin-derived responses in mice with an intact visual system, we reveal strong melanopsin input to the ∼40\% of neurons in the LGN that show sustained activation to a light step. We demonstrate that this melanopsin input supports irradiance-dependent increases in the firing rate of these neurons. The implication that melanopsin is required to accurately encode stimulus irradiance is confirmed using melanopsin knockout mice. Our data establish melanopsin-based photoreception as a significant source of sensory input to the thalamo-cortical visual system, providing unique irradiance information and allowing visual responses to be retained even in the absence of rods+cones. These findings identify mRGCs as a potential origin for aspects of visual perception and indicate that they may support vision in people suffering retinal degeneration.}, Author = {Brown, Timothy M and Gias, Carlos and Hatori, Megumi and Keding, Sheena R and Semo, Ma'ayan and Coffey, Peter J and Gigg, John and Piggins, Hugh D and Panda, Satchidananda and Lucas, Robert J}, Date-Added = {2011-03-07 13:33:22 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {retina;Photoreceptors;visual system;visual cortex;optic tectum}, Number = {12}, Pages = {e1000558}, Pmc = {PMC2998442}, pmid = {21151887}, Pst = {epublish}, Title = {Melanopsin contributions to irradiance coding in the thalamo-cortical visual system}, Volume = {8}, Year = {2010}, url = {papers/Brown_PLoSBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1000558}} @article{Yang:2009, Abstract = {Coordinated patterns of electrical activity are important for the early development of sensory systems. The spatiotemporal dynamics of these early activity patterns and the role of the peripheral sensory input for their generation are essentially unknown. We performed extracellular multielectrode recordings in the somatosensory cortex of postnatal day 0 to 7 rats in vivo and observed three distinct patterns of synchronized oscillatory activity. (1) Spontaneous and periphery-driven spindle bursts of 1-2 s in duration and approximately 10 Hz in frequency occurred approximately every 10 s. (2) Spontaneous and sensory-driven gamma oscillations of 150-300 ms duration and 30-40 Hz in frequency occurred every 10-30 s. (3) Long oscillations appeared only every approximately 20 min and revealed the largest amplitude (250-750 microV) and longest duration (>40 s). These three distinct patterns of early oscillatory activity differently synchronized the neonatal cortical network. Whereas spindle bursts and gamma oscillations did not propagate and synchronized a local neuronal network of 200-400 microm in diameter, long oscillations propagated with 25-30 microm/s and synchronized 600-800 microm large ensembles. All three activity patterns were triggered by sensory activation. Single electrical stimulation of the whisker pad or tactile whisker activation elicited neocortical spindle bursts and gamma activity. Long oscillations could be only evoked by repetitive sensory stimulation. The neonatal oscillatory patterns in vivo depended on NMDA receptor-mediated synaptic transmission and gap junctional coupling. Whereas spindle bursts and gamma oscillations may represent an early functional columnar-like pattern, long oscillations may serve as a propagating activation signal consolidating these immature neuronal networks.}, Author = {Yang, Jenq-Wei and Hanganu-Opatz, Ileana L and Sun, Jyh-Jang and Luhmann, Heiko J}, Date-Added = {2011-03-07 13:32:26 -0500}, Date-Modified = {2013-08-28 17:25:35 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development;Spontaneous activity;21 Cortical oscillations;Neocortex;21 Neurophysiology; in vivo; currOpinRvw}, Mesh = {Action Potentials; Age Factors; Amino Acids; Anesthetics, Local; Animals; Animals, Newborn; Biological Clocks; Brain Mapping; Electric Stimulation; Evoked Potentials, Somatosensory; Functional Laterality; Lidocaine; Nerve Net; Neurons; Rats; Somatosensory Cortex; Statistics, Nonparametric; Synaptic Transmission; Vibrissae}, Month = {Jul}, Number = {28}, Pages = {9011-25}, pmid = {19605639}, Pst = {ppublish}, Title = {Three patterns of oscillatory activity differentially synchronize developing neocortical networks in vivo}, Volume = {29}, Year = {2009}, url = {papers/Yang_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5646-08.2009}} @article{Miyamichi:2010, Abstract = {In the mouse, each class of olfactory receptor neurons expressing a given odorant receptor has convergent axonal projections to two specific glomeruli in the olfactory bulb, thereby creating an odour map. However, it is unclear how this map is represented in the olfactory cortex. Here we combine rabies-virus-dependent retrograde mono-trans-synaptic labelling with genetics to control the location, number and type of 'starter' cortical neurons, from which we trace their presynaptic neurons. We find that individual cortical neurons receive input from multiple mitral cells representing broadly distributed glomeruli. Different cortical areas represent the olfactory bulb input differently. For example, the cortical amygdala preferentially receives dorsal olfactory bulb input, whereas the piriform cortex samples the whole olfactory bulb without obvious bias. These differences probably reflect different functions of these cortical areas in mediating innate odour preference or associative memory. The trans-synaptic labelling method described here should be widely applicable to mapping connections throughout the mouse nervous system.}, Annote = {trans-synaptic labeling from colliculus to retina of strong synapse, which through recombination allows channelrhodopsin or halorhodopsin to be expressed, then repress or amplify activity in these strong synapse. Then do forward labeling of RGC axons to see percentage of contacts that stay in retinotopic regions or eye specific domains of colliculus.}, Author = {Miyamichi, Kazunari and Amat, Fernando and Moussavi, Farshid and Wang, Chen and Wickersham, Ian and Wall, Nicholas R and Taniguchi, Hiroki and Tasic, Bosiljka and Huang, Z Josh and He, Zhigang and Callaway, Edward M and Horowitz, Mark A and Luo, Liqun}, Date-Added = {2011-03-07 13:27:17 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {23 Technique;Viral;Gene Therapy;imaging;cell interaction;Synapses;frontiers review}, Month = {Dec}, pmid = {21179085}, Pst = {aheadofprint}, Title = {Cortical representations of olfactory input by trans-synaptic tracing}, Year = {2010}, url = {papers/Miyamichi_Nature2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature09714}} @article{Mahon:2009, Abstract = {Distinct regions within the ventral visual pathway show neural specialization for nonliving and living stimuli (e.g., tools, houses versus animals, faces). The causes of these category preferences are widely debated. Using functional magnetic resonance imaging, we find that the same regions of the ventral stream that show category preferences for nonliving stimuli and animals in sighted adults show the same category preferences in adults who are blind since birth. Both blind and sighted participants had larger blood oxygen-level dependent (BOLD) responses in the medial fusiform gyrus for nonliving stimuli compared to animal stimuli and differential BOLD responses in lateral occipital cortex for animal stimuli compared to nonliving stimuli. These findings demonstrate that the medial-to-lateral bias by conceptual domain in the ventral visual pathway does not require visual experience in order to develop and suggest the operation of innately determined domain-specific constraints on the organization of object knowledge.}, Author = {Mahon, Bradford Z and Anzellotti, Stefano and Schwarzbach, Jens and Zampini, Massimiliano and Caramazza, Alfonso}, Date-Added = {2011-03-07 13:24:05 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development;visual experimence;experience dependent plasticity;plasticity;Critical Period;Visual Cortex;visual system;development;human;fmri;Sensory Deprivation}, Mesh = {Acoustic Stimulation; Adult; Analysis of Variance; Blindness; Brain Mapping; Concept Formation; Female; Humans; Image Processing, Computer-Assisted; Judgment; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Oxygen; Pattern Recognition, Visual; Photic Stimulation; Reaction Time; Visual Cortex; Visual Pathways; Young Adult}, Month = {Aug}, Number = {3}, Pages = {397-405}, Pmc = {PMC2743253}, pmid = {19679078}, Pst = {ppublish}, Title = {Category-specific organization in the human brain does not require visual experience}, Volume = {63}, Year = {2009}, url = {papers/Mahon_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.07.012}} @article{McCarthy:2009, Abstract = {Alpha-herpesviruses, including human herpes simplex virus 1 \& 2, varicella zoster virus and the swine pseudorabies virus (PRV), infect the peripheral nervous system of their hosts. Symptoms of infection often include itching, numbness, or pain indicative of altered neurological function. To determine if there is an in vitro electrophysiological correlate to these characteristic in vivo symptoms, we infected cultured rat sympathetic neurons with well-characterized strains of PRV known to produce virulent or attenuated symptoms in animals. Whole-cell patch clamp recordings were made at various times after infection. By 8 hours of infection with virulent PRV, action potential (AP) firing rates increased substantially and were accompanied by hyperpolarized resting membrane potentials and spikelet-like events. Coincident with the increase in AP firing rate, adjacent neurons exhibited coupled firing events, first with AP-spikelets and later with near identical resting membrane potentials and AP firing. Small fusion pores between adjacent cell bodies formed early after infection as demonstrated by transfer of the low molecular weight dye, Lucifer Yellow. Later, larger pores formed as demonstrated by transfer of high molecular weight Texas red-dextran conjugates between infected cells. Further evidence for viral-induced fusion pores was obtained by infecting neurons with a viral mutant defective for glycoprotein B, a component of the viral membrane fusion complex. These infected neurons were essentially identical to mock infected neurons: no increased AP firing, no spikelet-like events, and no electrical or dye transfer. Infection with PRV Bartha, an attenuated circuit-tracing strain delayed, but did not eliminate the increased neuronal activity and coupling events. We suggest that formation of fusion pores between infected neurons results in electrical coupling and elevated firing rates, and that these processes may contribute to the altered neural function seen in PRV-infected animals.}, Author = {McCarthy, Kelly M and Tank, David W and Enquist, Lynn W}, Date-Added = {2011-03-07 13:21:08 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Pathog}, Journal-Full = {PLoS pathogens}, Keywords = {21 Activity-development;23 Technique;viral;Viral Envelope Proteins;21 Neurophysiology;Infection;pathology;cell interaction;Cell Adhesion;frontiers review}, Mesh = {Action Potentials; Animals; Cells, Cultured; Electrophysiology; Fluorescent Dyes; Giant Cells; Herpesvirus 1, Suid; Membrane Potentials; Neurons; Patch-Clamp Techniques; Pseudorabies; Rats; Rats, Sprague-Dawley; Superior Cervical Ganglion; Swine; Viral Envelope Proteins; Virus Internalization; Virus Replication}, Month = {Oct}, Number = {10}, Pages = {e1000640}, Pmc = {PMC2763221}, pmid = {19876391}, Pst = {ppublish}, Title = {Pseudorabies virus infection alters neuronal activity and connectivity in vitro}, Volume = {5}, Year = {2009}, url = {papers/McCarthy_PLoSPathog2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.ppat.1000640}} @article{Tsai:2009, Abstract = {Light influences sleep and alertness either indirectly through a well-characterized circadian pathway or directly through yet poorly understood mechanisms. Melanopsin (Opn4) is a retinal photopigment crucial for conveying nonvisual light information to the brain. Through extensive characterization of sleep and the electrocorticogram (ECoG) in melanopsin-deficient (Opn4(-/-)) mice under various light-dark (LD) schedules, we assessed the role of melanopsin in mediating the effects of light on sleep and ECoG activity. In control mice, a light pulse given during the habitual dark period readily induced sleep, whereas a dark pulse given during the habitual light period induced waking with pronounced theta (7-10 Hz) and gamma (40-70 Hz) activity, the ECoG correlates of alertness. In contrast, light failed to induce sleep in Opn4(-/-) mice, and the dark-pulse-induced increase in theta and gamma activity was delayed. A 24-h recording under a LD 1-hratio1-h schedule revealed that the failure to respond to light in Opn4(-/-) mice was restricted to the subjective dark period. Light induced c-Fos immunoreactivity in the suprachiasmatic nuclei (SCN) and in sleep-active ventrolateral preoptic (VLPO) neurons was importantly reduced in Opn4(-/-) mice, implicating both sleep-regulatory structures in the melanopsin-mediated effects of light. In addition to these acute light effects, Opn4(-/-) mice slept 1 h less during the 12-h light period of a LD 12ratio12 schedule owing to a lengthening of waking bouts. Despite this reduction in sleep time, ECoG delta power, a marker of sleep need, was decreased in Opn4(-/-) mice for most of the (subjective) dark period. Delta power reached after a 6-h sleep deprivation was similarly reduced in Opn4(-/-) mice. In mice, melanopsin's contribution to the direct effects of light on sleep is limited to the dark or active period, suggesting that at this circadian phase, melanopsin compensates for circadian variations in the photo sensitivity of other light-encoding pathways such as rod and cones. Our study, furthermore, demonstrates that lack of melanopsin alters sleep homeostasis. These findings call for a reevaluation of the role of light on mammalian physiology and behavior.}, Author = {Tsai, Jessica W and Hannibal, Jens and Hagiwara, Grace and Colas, Damien and Ruppert, Elisabeth and Ruby, Norman F and Heller, H Craig and Franken, Paul and Bourgin, Patrice}, Date-Added = {2011-03-07 13:13:39 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {development;Sleep;retina;Photoreceptors;visual system;}, Mesh = {Animals; Circadian Rhythm; Darkness; Electroencephalography; Galanin; Homeostasis; Light; Mice; Neurons; Preoptic Area; Proto-Oncogene Proteins c-fos; Rod Opsins; Sensory Gating; Sleep; Sleep, REM; Suprachiasmatic Nucleus; Time Factors; Wakefulness}, Month = {Jun}, Number = {6}, Pages = {e1000125}, Pmc = {PMC2688840}, pmid = {19513122}, Pst = {ppublish}, Title = {Melanopsin as a sleep modulator: circadian gating of the direct effects of light on sleep and altered sleep homeostasis in Opn4(-/-) mice}, Volume = {7}, Year = {2009}, url = {papers/Tsai_PLoSBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1000125}} @article{Brown:2003b, Abstract = {Neuroscientists associate the name of Donald O. Hebb with the Hebbian synapse and the Hebbian learning rule, which underlie connectionist theories and synaptic plasticity, but Hebb's work has also influenced developmental psychology, neuropsychology, perception and the study of emotions, as well as learning and memory. Here, we review the work of Hebb and its lasting influence on neuroscience in honour of the 2004 centenary of his birth.}, Author = {Brown, Richard E and Milner, Peter M}, Date-Added = {2011-03-07 13:11:56 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {21 Activity-development;hebbian;Cooperative Behavior;Competitive Behavior;cell interaction;review}, Mesh = {Animals; Canada; History, 20th Century; Humans; Neuropsychology; Neurosciences; Synapses; United States}, Month = {Dec}, Number = {12}, Pages = {1013-9}, pmid = {14682362}, Pst = {ppublish}, Title = {The legacy of Donald O. Hebb: more than the Hebb synapse}, Volume = {4}, Year = {2003}, url = {papers/Brown_NatRevNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1257}} @article{Bohland:2009, Abstract = {In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brainwide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brainwide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open-access data repository; compatibility with existing resources; and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.}, Author = {Bohland, Jason W and Wu, Caizhi and Barbas, Helen and Bokil, Hemant and Bota, Mihail and Breiter, Hans C and Cline, Hollis T and Doyle, John C and Freed, Peter J and Greenspan, Ralph J and Haber, Suzanne N and Hawrylycz, Michael and Herrera, Daniel G and Hilgetag, Claus C and Huang, Z Josh and Jones, Allan and Jones, Edward G and Karten, Harvey J and Kleinfeld, David and K{\"o}tter, Rolf and Lester, Henry A and Lin, John M and Mensh, Brett D and Mikula, Shawn and Panksepp, Jaak and Price, Joseph L and Safdieh, Joseph and Saper, Clifford B and Schiff, Nicholas D and Schmahmann, Jeremy D and Stillman, Bruce W and Svoboda, Karel and Swanson, Larry W and Toga, Arthur W and Van Essen, David C and Watson, James D and Mitra, Partha P}, Date-Added = {2011-03-07 13:09:32 -0500}, Date-Modified = {2012-08-23 18:13:54 +0000}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {neuroinformatics;20 Networks;connectivity;connectome;calcium imaging;Theoretical;Computational Biology;graph theory; next; wholeBrain}, Mesh = {Animals; Brain; Databases, Factual; Humans; Macaca; Mice; Models, Neurological; Nerve Net; Neuroanatomy; Research}, Month = {Mar}, Number = {3}, Pages = {e1000334}, Pmc = {PMC2655718}, pmid = {19325892}, Pst = {ppublish}, Title = {A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale}, Volume = {5}, Year = {2009}, url = {papers/Bohland_PLoSComputBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.1000334}} @article{Lopez-Bendito:2003, Author = {L{\'o}pez-Bendito, Guillermina and Moln{\'a}r, Zolt{\'a}n}, Date-Added = {2011-03-07 13:07:10 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Rev Neurosci}, Journal-Full = {Nature reviews. Neuroscience}, Keywords = {axon guidance;connectivity;Neocortex;development;review}, Mesh = {Animals; Body Patterning; Cell Communication; Cell Differentiation; Cerebral Cortex; Growth Cones; Growth Substances; Mice; Neural Pathways; Thalamus}, Month = {Apr}, Number = {4}, Pages = {276-89}, pmid = {12671644}, Pst = {ppublish}, Title = {Thalamocortical development: how are we going to get there?}, Volume = {4}, Year = {2003}, url = {papers/López-Bendito_NatRevNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1075}} @article{Desai:2010, Abstract = {Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific sub-circuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain, to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this 'opto-fMRI' approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI), and by analyzing how the set of regions recruited by optogenetically-driven SI activity differs between the awake and anesthetized states. Results demonstrated positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake as compared to anesthetized mice (0.7\% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies.}, Author = {Desai, Mitul and Kahn, Itamar and Knoblich, Ulf and Bernstein, Jacob and Atallah, Hisham and Yang, Aimei and Kopell, Nancy and Buckner, Randy L and Graybiel, Ann M and Moore, Christopher I and Boyden, Ed S}, Date-Added = {2011-03-07 12:59:04 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {fmri;in vivo;optogenetics;imaging;21 Neurophysiology;23 Technique;frontiers review}, Month = {Dec}, pmid = {21160013}, Pst = {aheadofprint}, Title = {Mapping Brain Networks in Awake Mice Using Combined Optical Neural Control and fMRI}, Year = {2010}, url = {papers/Desai_JNeurophysiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00828.2010}} @article{Niell:2010, Abstract = {Studies of visual processing in rodents have conventionally been performed on anesthetized animals, precluding examination of the effects of behavior on visually evoked responses. We have now studied the response properties of neurons in primary visual cortex of awake mice that were allowed to run on a freely rotating spherical treadmill with their heads fixed. Most neurons showed more than a doubling of visually evoked firing rate as the animal transitioned from standing still to running, without changes in spontaneous firing or stimulus selectivity. Tuning properties in the awake animal were similar to those measured previously in anesthetized animals. Response magnitude in the lateral geniculate nucleus did not increase with locomotion, demonstrating that the striking change in responsiveness did not result from peripheral effects at the eye. Interestingly, some narrow-spiking cells were spontaneously active during running but suppressed by visual stimuli. These results demonstrate powerful cell-type-specific modulation of visual processing by behavioral state in awake mice.}, Author = {Niell, Cristopher M and Stryker, Michael P}, Date-Added = {2011-03-07 12:54:21 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Neurophysiology;in vivo;23 Technique;21 Circuit structure-function;visual cortex;function;visual system}, Mesh = {Action Potentials; Animals; Behavior, Animal; Electrodes, Implanted; Electrophysiology; Evoked Potentials, Visual; Geniculate Bodies; Mice; Motor Activity; Neurons; Photic Stimulation; Visual Cortex; Visual Pathways}, Month = {Feb}, Number = {4}, Pages = {472-9}, pmid = {20188652}, Pst = {ppublish}, Title = {Modulation of visual responses by behavioral state in mouse visual cortex}, Volume = {65}, Year = {2010}, url = {papers/Niell_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.01.033}} @article{Nimmerjahn:2009, Abstract = {Although it is firmly established that neuronal activity is a prime determinant of animal behavior, relationships between astrocytic excitation and animal behavior have remained opaque. Cerebellar Bergmann glia are radial astrocytes that are implicated in motor behavior and exhibit Ca(2+) excitation. However, Ca(2+) excitation in these cells has not previously been studied in behaving animals. Using two-photon microscopy we found that Bergmann glia exhibit three forms of Ca(2+) excitation in awake, behaving mice. Two of these are ongoing within the cerebellar vermis. During locomotor performance concerted Ca(2+) excitation arises in networks of at least hundreds of Bergmann glia extending across several hundred microns or more. Concerted Ca(2+) excitation was abolished by anesthesia or blockade of either neural activity or glutamatergic transmission. Thus, large networks of Bergmann glia can be activated by specific animal behaviors and undergo excitation of sufficient magnitude to potentially initiate macroscopic changes in brain dynamics or blood flow.}, Author = {Nimmerjahn, Axel and Mukamel, Eran A and Schnitzer, Mark J}, Date-Added = {2011-03-07 12:52:20 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {multisensory integration;imaging;optogenetics;optical imaging;Optics;microscopy;calcium imaging;frontiers review;23 Technique;Software;Image Processing}, Mesh = {Animals; Astrocytes; Calcium Signaling; Cell Communication; Cerebellum; Male; Membrane Potentials; Mice; Mice, Inbred C57BL; Motor Activity; Motor Skills}, Month = {May}, Number = {3}, Pages = {400-12}, Pmc = {PMC2820366}, pmid = {19447095}, Pst = {ppublish}, Title = {Motor behavior activates Bergmann glial networks}, Volume = {62}, Year = {2009}, url = {papers/Nimmerjahn_Neuron2009.pdf}, Bdsk-File-2 = {papers/Nimmerjahn_Neuron2009.mov}, Bdsk-File-3 = {papers/Nimmerjahn_Neuron2009a.mov}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.03.019}} @article{Oka:2009, Abstract = {Sniffing is a characteristic odor sampling behavior in various mammalian species, which is associated with an increase in both nasal airflow rate and breathing frequency. Although the importance of sniffing in olfaction is well recognized, it has been challenging to separate the effect of airflow rate and sniffing frequency in vivo. In this study, we examined the individual effects of airflow rate and frequency on odorant responses of glomeruli in the mouse olfactory bulb (OB) using calcium imaging techniques and an artificial sniffing system. We found that nasal airflow rate, but not sniffing frequency, affected the apparent glomerular responses. When measured using OB imaging, apparent sensitivity for some of the odorants was significantly greater at the high nasal flow rates, while other odorants exhibited the opposite effect. In a single defined glomerulus, the sensitivity shift caused by changes in flow rate varied between odorants, suggesting that the flow rate effect is dependent on the chemical properties of an odorant rather than on the specific characteristics of the expressed olfactory receptor. Using natural flavors containing a variety of odorants, different glomerular activation patterns were observed between breathing and sniffing condition, likely due to odorant-dependent flow rate effects. Our results provide important information on in vivo odorant recognition and suggest that odor representation in the OB is not fixed but rather varies significantly depending on the respiratory state.}, Author = {Oka, Yuki and Takai, Yoshiki and Touhara, Kazushige}, Date-Added = {2011-03-07 12:50:48 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology;calcium imaging;imaging;optical imaging;Olfactory Bulb;in vivo;23 Technique;frontiers review;21 Circuit structure-function}, Mesh = {Animals; Dose-Response Relationship, Drug; Inhalation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nasal Mucosa; Odors; Olfactory Bulb; Receptors, Odorant; Sensory Thresholds; Smell; Time Factors}, Month = {Sep}, Number = {39}, Pages = {12070-8}, pmid = {19793965}, Pst = {ppublish}, Title = {Nasal airflow rate affects the sensitivity and pattern of glomerular odorant responses in the mouse olfactory bulb}, Volume = {29}, Year = {2009}, url = {papers/Oka_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1415-09.2009}} @article{OLeary:1994, Author = {O'Leary, D D and Schlaggar, B L and Tuttle, R}, Date-Added = {2011-03-07 12:48:52 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {development;neocortex;21 Activity-development;10 circuit formation;axon guidance;review}, Mesh = {Afferent Pathways; Animals; Axons; Cell Division; Cerebral Cortex; Humans; Neuronal Plasticity; Thalamus}, Pages = {419-39}, pmid = {8210182}, Pst = {ppublish}, Title = {Specification of neocortical areas and thalamocortical connections}, Volume = {17}, Year = {1994}, url = {papers/O'Leary_AnnuRevNeurosci1994.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.ne.17.030194.002223}} @article{Petros:2008, Abstract = {At the optic chiasm, retinal ganglion cell axons from each eye converge and segregate into crossed and uncrossed projections, a pattern critical for binocular vision. Here, we review recent findings on optic chiasm development, highlighting the specific transcription factors and guidance cues that implement retinal axon divergence into crossed and uncrossed pathways. Although mechanisms underlying the formation of the uncrossed projection have been identified, the means by which retinal axons are guided across the midline are still unclear. In addition to directives provided by transcription factors and receptors in the retina, gene expression in the ventral diencephalon influences chiasm formation. Throughout this review, we compare guidance mechanisms at the optic chiasm with those in other midline models and highlight unanswered questions both for retinal axon growth and axon guidance in general.}, Author = {Petros, Timothy J and Rebsam, Alexandra and Mason, Carol A}, Date-Added = {2011-03-07 12:44:37 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Keywords = {21 Activity-development;axon guidance;Optic Nerve;retina;development;LGN;visual system;review}, Mesh = {Animals; Brain; Functional Laterality; Gene Expression Regulation, Developmental; Growth Cones; Humans; Intercellular Signaling Peptides and Proteins; Optic Chiasm; Retina; Retinal Ganglion Cells; Vision, Binocular; Visual Pathways}, Pages = {295-315}, pmid = {18558857}, Pst = {ppublish}, Title = {Retinal axon growth at the optic chiasm: to cross or not to cross}, Volume = {31}, Year = {2008}, url = {papers/Petros_AnnuRevNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.31.060407.125609}} @article{Phan:2010, Abstract = {With its emphasis on minimally invasive high-speed imaging of intact tissues at depth, video-rate two-photon microscopy has revolutionized cell biology. This is particularly true in immunology, where the orchestration of cell migration, cell-cell interactions and intracellular signalling events in multiple distinct anatomical compartments within secondary lymphoid organs is fundamental for achieving an effective immune response. Until recently, access to this powerful tool has been limited to a handful of laboratories with the necessary skills and resources to either custom-build or purchase a commercial two-photon microscope. However, with the entry of more commercial vendors into the market and availability of turnkey solutions, two-photon microscopy is now becoming more accessible. Here, we discuss the practical aspects of establishing a basic intravital two-photon microscopy facility specifically for immunological research and how recent advances in ultrafast lasers, non-linear optics and localized photochemistry can be used to build more sophisticated instruments to support applications such as photoactivation and photobleaching, spectral fingerprinting and automated single-cell tracking. In addition, we discuss the next generation of fluorescent dyes and reporter mice and some of the microsurgical principles required to expose the relevant biology to interrogation by two-photon excitation.}, Author = {Phan, Tri Giang and Bullen, Andrew}, Date = {2010 May-Jun}, Date-Added = {2011-03-07 12:43:43 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Immunol Cell Biol}, Journal-Full = {Immunology and cell biology}, Keywords = {23 Technique;Multiphoton;microscopy;imaging;optical imaging;optics;in vivo}, Mesh = {Animals; Fluorescent Dyes; Humans; Immune System; Immunologic Techniques; Lasers; Mice; Microscopy, Fluorescence, Multiphoton; Research}, Number = {4}, Pages = {438-44}, pmid = {20066001}, Pst = {ppublish}, Title = {Practical intravital two-photon microscopy for immunological research: faster, brighter, deeper}, Volume = {88}, Year = {2010}, url = {papers/Phan_ImmunolCellBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/icb.2009.116}} @article{Cheung:2009, Abstract = {Although previous studies have shown that Braille reading and other tactile discrimination tasks activate the visual cortex of blind and sighted people, it is not known whether this kind of crossmodal reorganization is influenced by retinotopic organization. We have addressed this question by studying "S," a visually impaired adult with the rare ability to read print visually and Braille by touch. S had normal visual development until 6 years of age, and thereafter severe acuity reduction due to corneal opacification, but no evidence of visual-field loss. Functional magnetic resonance imaging revealed that, in S's early visual areas, tactile information processing activated what would be the foveal representation for normally sighted individuals, and visual information processing activated what would be the peripheral representation. Control experiments showed that this activation pattern was not due to visual imagery. S's high-level visual areas, which correspond to shape- and object-selective areas in normally sighted individuals, were activated by both visual and tactile stimuli. The retinotopically specific reorganization in early visual areas suggests an efficient redistribution of neural resources in the visual cortex.}, Author = {Cheung, Sing-Hang and Fang, Fang and He, Sheng and Legge, Gordon E}, Date-Added = {2011-03-07 12:40:13 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {21 Activity-development;visual cortex;development;plasticity;Sensory Deprivation;structural remodeling;retina;fmri;Critical Period;visual system;multisensory integration;somatotopy}, Mesh = {Adult; Brain Mapping; Child; Fovea Centralis; Humans; Magnetic Resonance Imaging; Male; Pattern Recognition, Physiological; Photic Stimulation; Touch; Touch Perception; Visual Cortex}, Month = {Apr}, Number = {7}, Pages = {596-601}, Pmc = {PMC2709730}, pmid = {19361999}, Pst = {ppublish}, Title = {Retinotopically specific reorganization of visual cortex for tactile pattern recognition}, Volume = {19}, Year = {2009}, url = {papers/Cheung_CurrBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2009.02.063}} @article{Rebsam:2009, Abstract = {Partial decussation of sensory pathways allows neural inputs from both sides of the body to project to the same target region where these signals will be integrated. Here, to better understand mechanisms of eye-specific targeting, we studied how retinal ganglion cell (RGC) axons terminate in their thalamic target, the dorsal lateral geniculate nucleus (dLGN), when crossing at the optic chiasm midline is altered. In models with gain- and loss-of-function of EphB1, the receptor that directs the ipsilateral projection at the optic chiasm, misrouted RGCs target the appropriate retinotopic zone in the opposite dLGN. However, in EphB1(-/-) mice, the misrouted axons do not intermingle with normally projecting RGC axons and segregate instead into a distinct patch. We also revisited the role of retinal activity on eye-specific targeting by blocking correlated waves of activity with epibatidine into both eyes. We show that, in wild-type mice, retinal waves are necessary during the first postnatal week for both proper distribution and eye-specific segregation of ipsilateral axons in the mature dLGN. Moreover, in EphB1(-/-) mice, refinement of ipsilateral axons is perturbed in control conditions and is further impaired after epibatidine treatment. Finally, retinal waves are required for the formation of the segregated patch of misrouted axons in EphB1(-/-) mice. These findings implicate molecular determinants for targeting of eye-specific zones that are independent of midline guidance cues and that function in concert with correlated retinal activity to sculpt retinogeniculate projections.}, Author = {Rebsam, Alexandra and Petros, Timothy J and Mason, Carol A}, Date-Added = {2011-03-07 12:36:54 -0500}, Date-Modified = {2012-07-06 13:39:40 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {development;retina;LGN;visual system;21 Activity-development;Spontaneous activity;axon guidance;Competitive Behavior;hebbian;retinal wave paper; Mouse}, Mesh = {Action Potentials; Animals; Bicyclo Compounds, Heterocyclic; Cues; Functional Laterality; Gene Expression Regulation, Developmental; Geniculate Bodies; Growth Cones; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurogenesis; Nicotinic Agonists; Pyridines; Receptor, EphB1; Retina; Retinal Ganglion Cells; Synapses; Synaptic Transmission; Vision, Ocular; Visual Pathways}, Month = {Nov}, Number = {47}, Pages = {14855-63}, Pmc = {PMC2829946}, pmid = {19940181}, Pst = {ppublish}, Title = {Switching retinogeniculate axon laterality leads to normal targeting but abnormal eye-specific segregation that is activity dependent}, Volume = {29}, Year = {2009}, url = {papers/Rebsam_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3462-09.2009}} @article{Ros:2009, Abstract = {Activity in neocortex is often characterized by synchronized oscillations of neurons and networks, resulting in the generation of a local field potential (LFP) and electroencephalogram. Do the neuronal networks of the cerebellum also generate synchronized oscillations and are they under the influence of those in the neocortex? Here we show that, in the absence of any overt external stimulus, the cerebellar cortex generates a slow oscillation that is correlated with that of the neocortex. Disruption of the neocortical slow oscillation abolishes the cerebellar slow oscillation, whereas blocking cerebellar activity has no overt effect on the neocortex. We provide evidence that the cerebellar slow oscillation results in part from the activation of granule, Golgi, and Purkinje neurons. In particular, we show that granule and Golgi cells discharge trains of single spikes, and Purkinje cells generate complex spikes, during the "up" state of the slow oscillation. Purkinje cell simple spiking is weakly related to the cerebellar and neocortical slow oscillation in a minority of cells. Our results indicate that the cerebellum generates rhythmic network activity that can be recorded as an LFP in the anesthetized animal, which is driven by synchronized oscillations of the neocortex. Furthermore, we show that correlations between neocortical and cerebellar LFPs persist in the awake animal, indicating that neocortical circuits modulate cerebellar neurons in a similar manner in natural behavioral states. Thus, the projection neurons of the neocortex collectively exert a driving and modulatory influence on cerebellar network activity.}, Author = {Ros, Hana and Sachdev, Robert N S and Yu, Yuguo and Sestan, Nenad and McCormick, David A}, Date-Added = {2011-03-07 11:58:21 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Cortical oscillations;Spontaneous activity;Sleep;21 Neurophysiology}, Mesh = {Action Potentials; Animals; Cerebellar Cortex; Male; Mice; Neocortex; Nerve Net; Neurons; Rats; Rats, Long-Evans; Rats, Sprague-Dawley}, Month = {Aug}, Number = {33}, Pages = {10309-20}, pmid = {19692605}, Pst = {ppublish}, Title = {Neocortical networks entrain neuronal circuits in cerebellar cortex}, Volume = {29}, Year = {2009}, url = {papers/Ros_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2327-09.2009}} @article{Piyawattanametha:2009, Abstract = {We present a two-photon microscope that is approximately 2.9 g in mass and 2.0 x 1.9 x 1.1 cm(3) in size and based on a microelectromechanical systems (MEMS) laser-scanning mirror. The microscope has a focusing motor and a micro-optical assembly composed of four gradient refractive index lenses and a dichroic microprism. Fluorescence is captured without the detected emissions reflecting off the MEMS mirror, by use of separate optical fibers for fluorescence collection and delivery of ultrashort excitation pulses. Using this microscope we imaged neocortical microvasculature and tracked the flow of erythrocytes in live mice.}, Author = {Piyawattanametha, Wibool and Cocker, Eric D and Burns, Laurie D and Barretto, Robert P and Jung, Juergen C and Ra, Hyejun and Solgaard, Olav and Schnitzer, Mark J}, Date-Added = {2011-03-07 11:54:48 -0500}, Date-Modified = {2011-03-07 11:54:48 -0500}, Journal = {Opt Lett}, Journal-Full = {Optics letters}, Mesh = {Animals; Brain; Capillaries; Computer-Aided Design; Equipment Design; Equipment Failure Analysis; Lenses; Mice; Micro-Electrical-Mechanical Systems; Microscopy, Fluorescence, Multiphoton; Miniaturization; Reproducibility of Results; Sensitivity and Specificity}, Month = {Aug}, Number = {15}, Pages = {2309-11}, Pmc = {PMC2826365}, pmid = {19649080}, Pst = {ppublish}, Title = {In vivo brain imaging using a portable 2.9 g two-photon microscope based on a microelectromechanical systems scanning mirror}, Volume = {34}, Year = {2009}, url = {papers/Piyawattanametha_OptLett2009.pdf}} @article{Miyawaki:2007, Author = {Miyawaki, Atsushi and Schnitzer, Mark J}, Date-Added = {2011-03-07 11:49:55 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {optogenetics;Imaging;23 Technique;optical imaging;Optics;Multiphoton;calcium imaging;frontiers review}, Mesh = {Animals; Humans; Neurosciences; Research}, Month = {Oct}, Number = {5}, Pages = {565-6}, pmid = {18093825}, Pst = {ppublish}, Title = {New technologies for neuroscience}, Volume = {17}, Year = {2007}, url = {papers/Miyawaki_CurrOpinNeurobiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2007.11.005}} @article{Flusberg:2008, Abstract = {A central goal in biomedicine is to explain organismic behavior in terms of causal cellular processes. However, concurrent observation of mammalian behavior and underlying cellular dynamics has been a longstanding challenge. We describe a miniaturized (1.1 g mass) epifluorescence microscope for cellular-level brain imaging in freely moving mice, and its application to imaging microcirculation and neuronal Ca(2+) dynamics.}, Author = {Flusberg, Benjamin A and Nimmerjahn, Axel and Cocker, Eric D and Mukamel, Eran A and Barretto, Robert P J and Ko, Tony H and Burns, Laurie D and Jung, Juergen C and Schnitzer, Mark J}, Date-Added = {2011-03-07 11:49:55 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optogenetics;Imaging;23 Technique;optical imaging;Optics;Multiphoton;calcium imaging;frontiers review;21 Neurophysiology;frontiers review}, Mesh = {Animals; Brain; Fiber Optic Technology; Mice; Microscopy, Fluorescence; Miniaturization; Movement; Time Factors}, Month = {Nov}, Number = {11}, Pages = {935-8}, Pmc = {PMC2828344}, pmid = {18836457}, Pst = {ppublish}, Title = {High-speed, miniaturized fluorescence microscopy in freely moving mice}, Volume = {5}, Year = {2008}, url = {papers/Flusberg_NatMethods2008.pdf}, Bdsk-File-2 = {papers/Flusberg_NatMethods2008a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1256}} @article{Shamir:2008, Abstract = {ABSTRACT:}, Author = {Shamir, Lior and Orlov, Nikita and Eckley, D Mark and Macura, Tomasz and Johnston, Josiah and Goldberg, Ilya G}, Date-Added = {2011-03-07 11:46:02 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Source Code Biol Med}, Journal-Full = {Source code for biology and medicine}, Keywords = {neuroinformatics;Image Processing;Software;Computational Biology;Computer Graphics}, Pages = {13}, Pmc = {PMC2478650}, pmid = {18611266}, Pst = {epublish}, Title = {Wndchrm - an open source utility for biological image analysis}, Volume = {3}, Year = {2008}, url = {papers/Shamir_SourceCodeBiolMed2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1751-0473-3-13}} @article{Sheroziya:2009, Abstract = {Periodic spontaneous activity represents an important attribute of the developing nervous system. The entorhinal cortex (EC) is a crucial component of the medial temporal lobe memory system. Yet, little is known about spontaneous activity in the immature EC. Here, we investigated spontaneous field potential (fp) activity and intrinsic firing patterns of medial EC layer III principal neurons in brain slices obtained from rats at the first two postnatal weeks. A fraction of immature layer III neurons spontaneously generated prolonged (2-20 s) voltage-dependent intrinsic bursting activity. Prolonged bursts were dependent on the extracellular concentration of Ca(2+) ([Ca(2+)](o)). Thus, reduction of [Ca(2+)](o) increased the fraction of neurons with prolonged bursting by inducing intrinsic bursts in regularly firing neurons. In 1 mm [Ca(2+)](o), the percentages of neurons showing prolonged bursts were 53\%, 81\%, and 29\% at postnatal day 5 (P5)-P7, P8-P10, and P11-P13, respectively. Prolonged intrinsic bursting activity was blocked by buffering intracellular Ca(2+) with BAPTA, and by Cd(2+), flufenamic acid (FFA), or TTX, and was suppressed by nifedipine and riluzole, suggesting that the Ca(2+)-sensitive nonspecific cationic current (I(CAN)) and the persistent Na(+) current (I(Nap)) underlie this effect. Indeed, a 0.2-1 s suprathreshold current step stimulus elicited a terminated plateau potential in these neurons. fp recordings at P5-P7 showed periodic spontaneous glutamate receptor-mediated events (sharp fp events or prolonged fp bursts) which were blocked by FFA. Slow-wave network oscillations become a dominant pattern at P11-P13. We conclude that prolonged intrinsic bursting activity is a characteristic feature of developing medial EC layer III neurons that might be involved in neuronal and network maturation.}, Author = {Sheroziya, Maxim G and von Bohlen Und Halbach, Oliver and Unsicker, Klaus and Egorov, Alexei V}, Date-Added = {2011-03-07 11:44:42 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Spontaneous activity;Neocortex;21 Activity-development;21 Cortical oscillations;in vitro;21 Neurophysiology;Patch-Clamp Techniques/methods}, Mesh = {6-Cyano-7-nitroquinoxaline-2,3-dione; Action Potentials; Age Factors; Animals; Animals, Newborn; Calcium; Egtazic Acid; Entorhinal Cortex; Neurons; Rats; Rats, Wistar}, Month = {Sep}, Number = {39}, Pages = {12131-44}, pmid = {19793971}, Pst = {ppublish}, Title = {Spontaneous bursting activity in the developing entorhinal cortex}, Volume = {29}, Year = {2009}, url = {papers/Sheroziya_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1333-09.2009}} @article{Shoham:2010, Author = {Shoham, Shy}, Date-Added = {2011-03-07 11:42:41 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {Microscopy;Optics;optical imaging;optogenetics;Multiphoton;23 Technique;frontiers review}, Mesh = {Animals; Brain; Computer Simulation; Mice; Neurons; Optics and Photonics; Photic Stimulation; Photons; Rhodopsin; Visual Pathways}, Month = {Oct}, Number = {10}, Pages = {798-9}, pmid = {20885441}, Pst = {ppublish}, Title = {Optogenetics meets optical wavefront shaping}, Volume = {7}, Year = {2010}, url = {papers/Shoham_NatMethods2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth1010-798}} @article{Muckli:2009, Abstract = {In mammals smooth retinotopic maps of the visual field are formed along the visual processing pathway whereby the left visual field is represented in the right hemisphere and vice versa. The reorganization of retinotopic maps in the lateral geniculate nucleus (LGN) of the thalamus and early visual areas (V1-V3) is studied in a patient who was born with only one cerebral hemisphere. Before the seventh week of embryonic gestation, the development of the patient's right cerebral hemisphere terminated. Despite the complete loss of her right hemisphere (di- and telencephalon) at birth, the patient's remaining hemisphere has not only developed maps of the contralateral (right) visual hemifield but, surprisingly, also maps of the ipsilateral (left) visual hemifield. Retinal ganglion-cells changed their predetermined crossing pattern in the optic chiasm and grew to the ipsilateral LGN. In the visual cortex, islands of ipsilateral visual field representations were located along the representations of the vertical meridian. In V1, smooth and continuous maps from contra- and ipsilateral hemifield overlap each other, whereas in ventral V2 and V3 ipsilateral quarter field representations invaded small distinct cortical patches. This reveals a surprising flexibility of the self-organizing developmental mechanisms responsible for map formation.}, Author = {Muckli, Lars and Naumer, Marcus J and Singer, Wolf}, Date-Added = {2011-03-07 11:34:22 -0500}, Date-Modified = {2011-09-13 08:34:14 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Activity-development;Spontaneous activity;retina;retinal wave paper;visual system;visual cortex;plasticity;Structure-Activity Relationship;structural remodeling;axon guidance;Superior Colliculus;optic tectum;21 Neurophysiology;human;cortical malformation;Optic Nerve;bilateral;sensory map; topographic map;human; mirror symmetry}, Mesh = {Brain; Brain Mapping; Child; Female; Geniculate Bodies; Humans; Magnetic Resonance Imaging; Microphthalmos; Optic Chiasm; Visual Fields}, Month = {Aug}, Number = {31}, Pages = {13034-9}, Pmc = {PMC2713389}, pmid = {19620732}, Pst = {ppublish}, Title = {Bilateral visual field maps in a patient with only one hemisphere}, Volume = {106}, Year = {2009}, url = {papers/Muckli_ProcNatlAcadSciUSA2009.pdf}, Bdsk-File-2 = {papers/Muckli_ProcNatlAcadSciUSA2009a.pdf}, Bdsk-File-3 = {papers/Muckli_ProcNatlAcadSciUSA2009b.pdf}, Bdsk-File-4 = {papers/Muckli_ProcNatlAcadSciUSA2009.avi}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0809688106}} @article{Singer:1995, Abstract = {One of the basic functions of the cerebral cortex is the analysis and representation of relations among the components of sensory and motor patterns. It is proposed that the cortex applies two complementary strategies to cope with the combinatorial problem posed by the astronomical number of possible relations: (i) the analysis and representation of frequently occurring, behaviorally relevant relations by groups of cells with fixed but broadly tuned response properties; and (ii) the dynamic association of these cells into functionally coherent assemblies. Feedforward connections and reciprocal associative connections, respectively, are thought to underlie these two operations. The architectures of both types of connections are susceptible to experience-dependent modifications during development, but they become fixed in the adult. As development proceeds, feedforward connections also appear to lose much of their functional plasticity, whereas the synapses of the associative connections retain a high susceptibility to use-dependent modifications. The reduced plasticity of feedforward connections is probably responsible for the invariance of cognitive categories acquired early in development. The persistent adaptivity of reciprocal connections is a likely substrate for the ability to generate representations for new perceptual objects and motor patterns throughout life.}, Author = {Singer, W}, Date-Added = {2011-03-07 11:29:58 -0500}, Date-Modified = {2011-03-07 11:32:02 -0500}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Activity-development;development;21 Cortical oscillations;21 Neurophysiology;plasticity;Critical Period;Calcium;Calcium Channels;Theoretical;20 Networks;Visual Cortex;visual system;LGN;retina;Spontaneous activity}, Mesh = {Action Potentials; Animals; Brain Mapping; Cerebral Cortex; Long-Term Potentiation; Neural Pathways; Neuronal Plasticity; Neurons; Receptors, N-Methyl-D-Aspartate; Retinal Ganglion Cells; Synapses; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Nov}, Number = {5237}, Pages = {758-64}, pmid = {7481762}, Pst = {ppublish}, Title = {Development and plasticity of cortical processing architectures}, Volume = {270}, Year = {1995}, url = {papers/Singer_Science1995.pdf}} @article{Lansford:2001, Abstract = {The imaging of living cells and tissues using laser-scanning microscopy is offering dramatic insights into the spatial and temporal controls of biological processes. The availability of genetically encoded labels such as green fluorescent protein (GFP) offers unique opportunities by which to trace cell movements, cell signaling or gene expression dynamically in developing embryos. Two-photon laser scanning microscopy (TPLSM) is ideally suited to imaging cells in vivo due to its deeper tissue penetration and reduced phototoxicity; however, in TPLSM the excitation and emission spectra of GFP and its color variants [e.g., CyanFP (CFP); yellowFP (YFP)] are insufficiently distinct to be uniquely imaged by conventional means. To surmount such difficulties, we have combined the technologies of TPLSM and imaging spectroscopy to unambiguously identify CFP, GFP, YFP, and redFP (RFP) as well as conventional dyes, and have tested the approach in cell lines. In our approach, a liquid crystal tunable filter was used to collect the emission spectrum of each pixel within the TPLSM image. Based on the fluorescent emission spectra, supervised classification and linear unmixing analysis algorithms were used to identify the nature and relative amounts of the fluorescent proteins expressed in the cells. In a most extreme case, we have used the approach to separate GFP and fluorescein, separated by only 7 nm, and appear somewhat indistinguishable by conventional techniques. This approach offers the needed ability to concurrently image multiple colored, spectrally overlapping marker proteins within living cells.}, Author = {Lansford, R and Bearman, G and Fraser, S E}, Date-Added = {2011-03-07 11:26:40 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Biomed Opt}, Journal-Full = {Journal of biomedical optics}, Keywords = {23 Technique;Imaging;Image Processing;Optics;Multiphoton;Microscopy}, Mesh = {Algorithms; Animals; Chick Embryo; Color; Coloring Agents; Diagnostic Imaging; Fluorescein; Fluorescent Dyes; Green Fluorescent Proteins; Humans; Indicators and Reagents; Luminescent Proteins; Microscopy, Fluorescence; Photons; Spectrum Analysis}, Month = {Jul}, Number = {3}, Pages = {311-8}, pmid = {11516321}, Pst = {ppublish}, Title = {Resolution of multiple green fluorescent protein color variants and dyes using two-photon microscopy and imaging spectroscopy}, Volume = {6}, Year = {2001}, url = {papers/Lansford_JBiomedOpt2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1117/1.1383780}} @article{Spiegel:2008, Abstract = {Physiological interactions between the nervous and immune systems with components of the local microenvironment are needed to maintain homeostasis throughout the body. Dynamic regulation of bone remodeling, hematopoietic stem cells, and their evolving niches via neurotransmitter signaling are part of the host defense and repair mechanisms. This crosstalk links activated leukocytes, neuronal, and stromal cells, which combine to directly and indirectly regulate hematopoietic stem cells. Together, interactions between diverse systems create a regulatory "brain-bone-blood triad," contributing an additional dimension to the concept of the hematopoietic stem cell niche.}, Author = {Spiegel, Asaf and Kalinkovich, Alexander and Shivtiel, Shoham and Kollet, Orit and Lapidot, Tsvee}, Date-Added = {2011-03-07 11:23:35 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Cell Stem Cell}, Journal-Full = {Cell stem cell}, Keywords = {Stem Cells;Neuron-Glia/*physiology;neuron;development;Immune System;macrophage;microglia;Cooperative Behavior;glia;Cell Adhesion;cell interaction}, Mesh = {Animals; Cell Differentiation; Cell Movement; Circadian Rhythm; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cells; Homeostasis; Humans; Neuroimmunomodulation; Paracrine Communication; Stem Cell Niche; Stress, Physiological}, Month = {Nov}, Number = {5}, Pages = {484-92}, pmid = {18983964}, Pst = {ppublish}, Title = {Stem cell regulation via dynamic interactions of the nervous and immune systems with the microenvironment}, Volume = {3}, Year = {2008}, url = {papers/Spiegel_CellStemCell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.stem.2008.10.006}} @article{Huang:2010, Abstract = {Although spiral waves are ubiquitous features of nature and have been observed in many biological systems, their existence and potential function in mammalian cerebral cortex remain uncertain. Using voltage-sensitive dye imaging, we found that spiral waves occur frequently in the neocortex in vivo, both during pharmacologically induced oscillations and during sleep-like states. While their life span is limited, spiral waves can modify ongoing cortical activity by influencing oscillation frequencies and spatial coherence and by reducing amplitude in the area surrounding the spiral phase singularity. During sleep-like states, the rate of occurrence of spiral waves varies greatly depending on brain states. These results support the hypothesis that spiral waves, as an emergent activity pattern, can organize and modulate cortical population activity on the mesoscopic scale and may contribute to both normal cortical processing and to pathological patterns of activity such as those found in epilepsy.}, Author = {Huang, Xiaoying and Xu, Weifeng and Liang, Jianmin and Takagaki, Kentaroh and Gao, Xin and Wu, Jian-Young}, Date-Added = {2011-03-07 11:20:42 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Spontaneous activity;Neocortex;21 Cortical oscillations;20 Networks;Theoretical;Computational Biology;Acetylcholine;Imaging;optical imaging;21 Neurophysiology;in vivo;voltage sensor;optical physiology;rat}, Mesh = {Animals; Brain Waves; Models, Neurological; Neocortex; Oscillometry; Rats; Rats, Sprague-Dawley; Sleep; Voltage-Sensitive Dye Imaging}, Month = {Dec}, Number = {5}, Pages = {978-90}, pmid = {21145009}, Pst = {ppublish}, Title = {Spiral wave dynamics in neocortex}, Volume = {68}, Year = {2010}, url = {papers/Huang_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.11.007}} @article{Dani:2010, Abstract = {Determination of the molecular architecture of synapses requires nanoscopic image resolution and specific molecular recognition, a task that has so far defied many conventional imaging approaches. Here, we present a superresolution fluorescence imaging method to visualize the molecular architecture of synapses in the brain. Using multicolor, three-dimensional stochastic optical reconstruction microscopy, the distributions of synaptic proteins can be measured with nanometer precision. Furthermore, the wide-field, volumetric imaging method enables high-throughput, quantitative analysis of a large number of synapses from different brain regions. To demonstrate the capabilities of this approach, we have determined the organization of ten protein components of the presynaptic active zone and the postsynaptic density. Variations in synapse morphology, neurotransmitter receptor composition, and receptor distribution were observed both among synapses and across different brain regions. Combination with optogenetics further allowed molecular events associated with synaptic plasticity to be resolved at the single-synapse level.}, Author = {Dani, Adish and Huang, Bo and Bergan, Joseph and Dulac, Catherine and Zhuang, Xiaowei}, Date-Added = {2011-03-07 11:18:16 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {23 Technique;Microscopy;Synaptic Transmission;Synaptic Membranes;Synapses;Optics;Imaging;frontiers review}, Mesh = {Animals; Brain; Brain Chemistry; Image Processing, Computer-Assisted; Imaging, Three-Dimensional; Immunohistochemistry; Mice; Mice, Inbred C57BL; Microchemistry; Microscopy, Fluorescence; Molecular Imaging; Nanotechnology; Nerve Tissue Proteins; Neuronal Plasticity; Photomicrography; Presynaptic Terminals; Stochastic Processes; Synapses}, Month = {Dec}, Number = {5}, Pages = {843-56}, pmid = {21144999}, Pst = {ppublish}, Title = {Superresolution imaging of chemical synapses in the brain}, Volume = {68}, Year = {2010}, url = {papers/Dani_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.11.021}} @article{Yazaki-Sugiyama:2009, Abstract = {Experience-dependent plasticity in the brain requires balanced excitation-inhibition. How individual circuit elements contribute to plasticity outcome in complex neocortical networks remains unknown. Here we report an intracellular analysis of ocular dominance plasticity-the loss of acuity and cortical responsiveness for an eye deprived of vision in early life. Unlike the typical progressive loss of pyramidal-cell bias, direct recording from fast-spiking cells in vivo reveals a counterintuitive initial shift towards the occluded eye followed by a late preference for the open eye, consistent with a spike-timing-dependent plasticity rule for these inhibitory neurons. Intracellular pharmacology confirms a dynamic switch of GABA (gamma-aminobutyric acid) impact to pyramidal cells following deprivation in juvenile mice only. Together these results suggest that the bidirectional recruitment of an initially binocular GABA circuit may contribute to experience-dependent plasticity in the developing visual cortex.}, Author = {Yazaki-Sugiyama, Yoko and Kang, Siu and C{\^a}teau, Hideyuki and Fukai, Tomoki and Hensch, Takao K}, Date-Added = {2011-03-07 11:15:14 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Activity-development;GABA;12 Interneuron development;10 circuit formation;development;Neocortex;Visual Cortex;Sensory Deprivation;plasticity;Critical Period}, Mesh = {Action Potentials; Aging; Animals; Dominance, Ocular; Interneurons; Mice; Mice, Inbred C57BL; Models, Neurological; Neuronal Plasticity; Neurons; Photic Stimulation; Pyramidal Cells; Receptors, GABA; Visual Cortex; Visual Pathways; Visual Perception; gamma-Aminobutyric Acid}, Month = {Nov}, Number = {7270}, Pages = {218-21}, pmid = {19907494}, Pst = {ppublish}, Title = {Bidirectional plasticity in fast-spiking GABA circuits by visual experience}, Volume = {462}, Year = {2009}, url = {papers/Yazaki-Sugiyama_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature08485}} @article{Tian:2008, Abstract = {A fundamental feature of the synaptic organization of retina is the laminar-specific structure, in which specific types of retinal neurons form highly selective synapses to transfer distinct synaptic signals. In mature vertebrate retina, the dendrites of most retinal ganglion cells (RGCs) are narrowly stratified and ramified in specific strata of the inner plexiform layer (IPL) of retina to synapse with distinct subtypes of bipolar cells (BCs). However, little is known of how retinal neurons form this laminar-specific synaptic structure during development. Recent studies showed that the formation of retinal synaptic circuitry is regulated by both gene expression and neuronal activity. Here I will briefly discuss the recent advances in our understanding of how synaptic activity modulates the maturation of RGC synaptic connections.}, Author = {Tian, Ning}, Date-Added = {2011-03-07 11:12:30 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Physiol}, Journal-Full = {The Journal of physiology}, Keywords = {21 Activity-development;21 Neurophysiology;development;visual system;retina;retinal wave paper;10 circuit formation;Spontaneous activity}, Mesh = {Animals; Animals, Newborn; Light; Neurogenesis; Retina; Retinal Ganglion Cells; Synapses; Visual Pathways}, Month = {Sep}, Number = {Pt 18}, Pages = {4347-55}, Pmc = {PMC2614011}, pmid = {18669531}, Pst = {ppublish}, Title = {Synaptic activity, visual experience and the maturation of retinal synaptic circuitry}, Volume = {586}, Year = {2008}, url = {papers/Tian_JPhysiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2008.159202}} @article{Tyzio:2009, Abstract = {The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies.}, Author = {Tyzio, Roman and Khalilov, Ilgam and Represa, Alfonso and Crepel, Valerie and Zilberter, Yuri and Rheims, Sylvain and Aniksztejn, Laurent and Cossart, Rosa and Nardou, Romain and Mukhtarov, Marat and Minlebaev, Marat and Epsztein, J{\'e}r{\^o}me and Milh, Mathieu and Becq, Helene and Jorquera, Isabel and Bulteau, Christine and Fohlen, Martine and Oliver, Viviana and Dulac, Olivier and Dorfm{\"u}ller, Georg and Delalande, Olivier and Ben-Ari, Yehezkel and Khazipov, Roustem}, Date-Added = {2011-03-07 11:07:59 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Ann Neurol}, Journal-Full = {Annals of neurology}, Keywords = {21 Activity-development; gaba; Excitatory Amino Acids;Epilepsy;Seizures;cortical malformation;Neocortex/*abnormalities/pathology}, Mesh = {Action Potentials; Bumetanide; Cerebral Cortex; Diazepam; Epilepsy; Excitatory Amino Acid Antagonists; GABA Agonists; GABA Modulators; GABA-A Receptor Agonists; Humans; Infant; Isonicotinic Acids; Membrane Potentials; Neural Inhibition; Neurons; Receptors, GABA-A; Receptors, Glutamate; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Potassium-Chloride Symporters; Sturge-Weber Syndrome; gamma-Aminobutyric Acid}, Month = {Aug}, Number = {2}, Pages = {209-18}, pmid = {19743469}, Pst = {ppublish}, Title = {Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndrome}, Volume = {66}, Year = {2009}, url = {papers/Tyzio_AnnNeurol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.21711}} @article{Uhlhaas:2009, Abstract = {Brain development is characterized by maturational processes that span the period from childhood through adolescence to adulthood, but little is known whether and how developmental processes differ during these phases. We analyzed the development of functional networks by measuring neural synchrony in EEG recordings during a Gestalt perception task in 68 participants ranging in age from 6 to 21 years. Until early adolescence, developmental improvements in cognitive performance were accompanied by increases in neural synchrony. This developmental phase was followed by an unexpected decrease in neural synchrony that occurred during late adolescence and was associated with reduced performance. After this period of destabilization, we observed a reorganization of synchronization patterns that was accompanied by pronounced increases in gamma-band power and in theta and beta phase synchrony. These findings provide evidence for the relationship between neural synchrony and late brain development that has important implications for the understanding of adolescence as a critical period of brain maturation.}, Author = {Uhlhaas, Peter J and Roux, Frederic and Singer, Wolf and Haenschel, Corinna and Sireteanu, Ruxandra and Rodriguez, Eugenio}, Date-Added = {2011-03-07 11:06:19 -0500}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Spontaneous activity; Human;21 Activity-development; 21 Neurophysiology;21 Cortical oscillations}, Mesh = {Adolescent; Adult; Brain; Child; Electroencephalography; Female; Humans; Magnetic Resonance Imaging; Male}, Month = {Jun}, Number = {24}, Pages = {9866-71}, Pmc = {PMC2687997}, pmid = {19478071}, Pst = {ppublish}, Title = {The development of neural synchrony reflects late maturation and restructuring of functional networks in humans}, Volume = {106}, Year = {2009}, url = {papers/Uhlhaas_ProcNatlAcadSciUSA2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0900390106}} @article{Koch:2010, Abstract = {Neuronal pentraxins (NPs) are hypothesized to play important roles in the recruitment of AMPA receptors (AMPARs) to immature synapses, yet a physiological role for NPs at nascent synapses in vivo has remained elusive. Here we report that the loss of NP1 and NP2 (NP1/2) leads to a dramatic and specific reduction in AMPAR-mediated transmission at developing visual system synapses. In thalamic slices taken from early postnatal mice (pentobarbitone>chlordiazepoxide, and potencies on the basis of EC(50) estimates, chlordiazepoxide>propofol>pentobarbitone. The greater than expected GABA potentiating properties of propofol were explained by a direct hyperpolarising action that occurred in the same concentration range as its action at the GABA(A) receptor but that was unlikely to be mediated by GABA(A) receptors.}, Author = {Empson, R M and Sheardown, M J and Newberry, N R}, Date-Added = {2010-09-15 16:12:25 -0400}, Date-Modified = {2010-09-15 16:20:22 -0400}, Journal = {Eur J Pharmacol}, Journal-Full = {European journal of pharmacology}, Keywords = {optic tectum; superior colliculus; connectivity; gaba; retina gaba paper}, Mesh = {Animals; Chlordiazepoxide; Dose-Response Relationship, Drug; Drug Synergism; Electrophysiology; Male; Optic Nerve; Pentobarbital; Propofol; Rats; Rats, Sprague-Dawley; Receptors, GABA-A; gamma-Aminobutyric Acid}, Month = {Aug}, Number = {3}, Pages = {339-42}, pmid = {10936491}, Pst = {ppublish}, Title = {Modulation of gamma-aminobutyric acid responses in the rat optic nerve}, Volume = {401}, Year = {2000}, url = {papers/Empson_EurJPharmacol2000.pdf}} @article{Costa:1997, Abstract = {GABA immunoreactivity was examined in the retina of the New World monkey Cebus apella. Labeled cell bodies were identified as horizontal, bipolar, interplexiform, amacrine and a population of putative ganglion cells. To determine whether ganglion cells were immunoreactive to GABA, double-labeling experiments were performed using Fast Blue as retrograde neuronal tracer injected into the superior colliculus. Retinas containing FB-labeled ganglion cells were subsequently incubated with antiserum against GABA. Although retinocollicular ganglion cells were found in three different layers (ganglion cell layer, inner nuclear layer and inner plexiform layer), our experiments revealed GABA-positive ganglion cells only in the outer half of the ganglion cell layer.}, Author = {da Costa, B L and Hoko{\c c}, J N and Pinaud, R R and Gattass, R}, Date-Added = {2010-09-15 16:12:25 -0400}, Date-Modified = {2010-09-15 16:20:22 -0400}, Journal = {Neuroreport}, Journal-Full = {Neuroreport}, Keywords = {optic tectum; superior colliculus; connectivity; gaba; retina gaba paper}, Mesh = {Amidines; Animals; Cebus; Fluorescent Dyes; Immunohistochemistry; Male; Retina; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways; gamma-Aminobutyric Acid}, Month = {May}, Number = {8}, Pages = {1797-802}, pmid = {9223054}, Pst = {ppublish}, Title = {GABAergic retinocollicular projection in the New World monkey Cebus apella}, Volume = {8}, Year = {1997}, url = {papers/Costa_Neuroreport1997.pdf}} @article{Wilson:1996, Abstract = {Using an antibody to gamma-aminobutyric acid (GABA), we examined the optic nerves and optic tracts from macaque monkeys at the light and electron microscopic levels to determine if there is a possible inhibitory projection from the retina to the brain. All of the monkeys (n = 5) had GABA immunopositive axons that were evenly distributed in their optic nerves. These immunopositive axons were slightly larger than the axons around them and comprised an average of 2.6\% of the axons in the nerves. Thus, their estimated total was about 44,000 axons per nerve. In the optic tracts, the GABA immunopositive axons were not distributed evenly, but were concentrated mostly in the ventromedial part, indicating that this retinal pathway probably goes to a midbrain destination such as the superior colliculus. The present findings provide further evidence that there is a GABAergic retinal projection to the brain in primates with currently unknown physiological influences.}, Author = {Wilson, J R and Cowey, A and Somogy, P}, Date-Added = {2010-09-15 16:12:25 -0400}, Date-Modified = {2010-09-15 16:20:22 -0400}, Journal = {Vision Res}, Journal-Full = {Vision research}, Keywords = {optic tectum; superior colliculus; connectivity; gaba; retina gaba paper}, Mesh = {Animals; Axons; Biometry; Cell Count; Immunohistochemistry; Macaca fascicularis; Macaca mulatta; Mesencephalon; Microscopy, Electron; Neural Pathways; Optic Nerve; gamma-Aminobutyric Acid}, Month = {May}, Number = {10}, Pages = {1357-63}, pmid = {8762755}, Pst = {ppublish}, Title = {GABA immunopositive axons in the optic nerve and optic tract of macaque monkeys}, Volume = {36}, Year = {1996}, url = {papers/Wilson_VisionRes1996.pdf}} @article{Lugo-Garcia:1991, Abstract = {Glutamic acid decarboxylase (GAD)- and gamma-aminobutyric acid (GABA)-like immunoreactivity was examined in the retina of the 13-lined ground squirrel (Spermophilus tridecemlineatus). Labeling was observed in the inner nuclear layer (INL), inner plexiform layer (IPL) and ganglion cell layer (GCL). The immunoreactive cell bodies in the inner third of the INL were 6-13 microns in diameter and, because of their size and location it was considered that these were amacrine cells. Labeling in the IPL was concentrated in 5 bands corresponding to laminae 1a, 1c, 2, 4 and 5. In the GCL a heterogeneous population of neurons exhibited GAD- and GABA-like immunoreactivity. The soma diameters of the GCL cells ranged from 5 to 17 microns. These may represent displaced amacrines and/or ganglion cells. To determine if any of the immunoreactive cells in the GCL were ganglion cells, double labeling experiments were performed using rhodamine latex microspheres ('beads') as retrograde neuronal tracers. Rhodamine beads were injected into the superior colliculus, and retinas with retrogradely labeled ganglion cells were subsequently incubated with the anti-GAD antiserum. These experiments revealed a small population of GAD-positive ganglion cells, setting a lower limit for the total number of GABAergic ganglion cells.}, Author = {Lugo-Garc{\'\i}a, N and Blanco, R E}, Date-Added = {2010-09-15 16:12:25 -0400}, Date-Modified = {2010-09-15 16:20:22 -0400}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {optic tectum; superior colliculus; connectivity; gaba; retina gaba paper}, Mesh = {Animals; Avidin; Biotin; Fluorescent Antibody Technique; Glutamate Decarboxylase; Immunohistochemistry; Mesencephalon; Microspheres; Retina; Retinal Ganglion Cells; Sciuridae; Stereotaxic Techniques; gamma-Aminobutyric Acid}, Month = {Nov}, Number = {1}, Pages = {19-26}, pmid = {1777820}, Pst = {ppublish}, Title = {Localization of GAD- and GABA-like immunoreactivity in ground squirrel retina: retrograde labeling demonstrates GAD-positive ganglion cells}, Volume = {564}, Year = {1991}, url = {papers/Lugo-García_BrainRes1991.pdf}} @article{Caruso:1989, Abstract = {Ganglion cells in the rat retina were labeled with the fluorescent dye, Diamidino-yellow, by retrograde transport from the superior colliculus and subsequently reacted for GABA-like immunoreactivity with a rhodamine-conjugated antiserum. Examination of sectioned retinas by fluorescence microscopy showed double labeling in approximately 6\% of the ganglion cells. The presence of GABA in these neurons suggests that they may be involved in providing direct inhibitory input to the rat tectum.}, Author = {Caruso, D M and Owczarzak, M T and Goebel, D J and Hazlett, J C and Pourcho, R G}, Date-Added = {2010-09-15 16:12:25 -0400}, Date-Modified = {2010-09-15 16:20:22 -0400}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {optic tectum; superior colliculus; connectivity; gaba; retina gaba paper}, Mesh = {Animals; Immunohistochemistry; Rats; Retina; Retinal Ganglion Cells; gamma-Aminobutyric Acid}, Month = {Jan}, Number = {1}, Pages = {129-34}, pmid = {2914207}, Pst = {ppublish}, Title = {GABA-immunoreactivity in ganglion cells of the rat retina}, Volume = {476}, Year = {1989}, url = {papers/Caruso_BrainRes1989.pdf}} @article{May:2006, Abstract = {The superior colliculus is a laminated midbrain structure that acts as one of the centers organizing gaze movements. This review will concentrate on sensory and motor inputs to the superior colliculus, on its internal circuitry, and on its connections with other brainstem gaze centers, as well as its extensive outputs to those structures with which it is reciprocally connected. This will be done in the context of its laminar arrangement. Specifically, the superficial layers receive direct retinal input, and are primarily visual sensory in nature. They project upon the visual thalamus and pretectum to influence visual perception. These visual layers also project upon the deeper layers, which are both multimodal, and premotor in nature. Thus, the deep layers receive input from both somatosensory and auditory sources, as well as from the basal ganglia and cerebellum. Sensory, association, and motor areas of cerebral cortex provide another major source of collicular input, particularly in more encephalized species. For example, visual sensory cortex terminates superficially, while the eye fields target the deeper layers. The deeper layers are themselves the source of a major projection by way of the predorsal bundle which contributes collicular target information to the brainstem structures containing gaze-related burst neurons, and the spinal cord and medullary reticular formation regions that produce head turning.}, Author = {May, Paul J}, Date-Added = {2010-09-15 16:01:11 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Prog Brain Res}, Journal-Full = {Progress in brain research}, Keywords = {optic tectum;Superior Colliculus;connectivity;function;retina gaba paper}, Mesh = {Animals; Arousal; Auditory Perception; Brain Stem; Cerebellum; Cerebral Cortex; Ear, External; Eye Movements; Fixation, Ocular; Haplorhini; Mammals; Neural Pathways; Neurons; Rats; Retina; Spinal Cord; Superior Colliculi; Thalamus; Visual Perception}, Pages = {321-78}, pmid = {16221594}, Pst = {ppublish}, Title = {The mammalian superior colliculus: laminar structure and connections}, Volume = {151}, Year = {2006}, url = {papers/May_ProgBrainRes2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0079-6123(05)51011-2}} @article{Abrahams:1975, Abstract = {Unit recordings were made in the superior colliculus of cats anesthetized with chloralose and with Pentothal. Electrical stimulation of extraocular muscle afferents and neck muscle afferents excited more units in the superior colliculus than did a variety of moving and stationary visual stimuli. Units responding to neck muscle afferent stimulation fell into three populations; one population firing with a short latency and following stimulus presentation up to 1/s, a second population with a long latency and following stimulus presentation at frequencies lower than 15/min, and a third population exhibiting paired firing. The latencies and firing patterns of the third population combined the characteristics of each of the first two patterns. It is suggested that these characteristics of unit discharges stem from the existence of two pathways from neck muscle afferents to the superior colliculus. The projection is predominantly bilateral. Units responding to neck muscle afferent stimulation are distributed throughout the superior colliculus on the basis of their latencies. Long-latency responses predominate in the superficial layers of the superior colliculus and short-latency responses, while more common in the intermediate and deep layers, predominate in the tegmentum. Extraocular muscle afferent projections to the superior colliculus constitute the single richest projection found in these experiments. While the response patterns and latencies are similar to those of the neck muscle afferents, long-latency responses are the most common and dominate in all collicular regions. Few units in the tegmentum could be excited by extraocular muscle afferents. Both extraocular muscle and neck muscle afferents show considerable convergence with one another and with retinal afferents within the superior colliculus. Cells of origin of the tectospinal tract were identified within the superior colliculus and tegmentum by antidromic excitation from the upper cervical cord. These cells were distributed predominantly within the intermediate and deep layers of the superior colliculus, and sparsely in the superficial layers and tegmentum. Almost 50\% of the cells of origin of the tectospinal tract receive a convergent input from extraocular muscle and neck muscle afferents and from the retina. About 30\% of the cells were inexcitable to the stimuli employed in these experiments. The significance of these projections is discussed with respect to superior collicular function in the cat and i}, Author = {Abrahams, V C and Rose, P K}, Date-Added = {2010-09-15 15:50:36 -0400}, Date-Modified = {2010-09-15 15:54:04 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {21 Neurophysiology;21 Circuit structure-function;Superior Colliculus;optic tectum;Vision;connectivity;Efferent Pathways;Afferent Pathways}, Mesh = {Anesthesia, General; Animals; Cats; Electric Stimulation; Evoked Potentials; Head; Microelectrodes; Movement; Muscle Denervation; Neck; Neurons; Neurons, Afferent; Oculomotor Muscles; Physical Stimulation; Reaction Time; Retina; Spinal Cord; Superior Colliculi; Synaptic Transmission; Vision, Ocular}, Month = {Jan}, Number = {1}, Pages = {10-8}, pmid = {162939}, Pst = {ppublish}, Title = {Projections of extraocular, neck muscle, and retinal afferents to superior colliculus in the cat: their connections to cells of origin of tectospinal tract}, Volume = {38}, Year = {1975}, url = {papers/Abrahams_JNeurophysiol1975.pdf}} @article{Meredith:1985, Abstract = {By means of their efferent projections to motor and premotor structures, the cells in the deep superior colliculus are intimately involved in behaviors that control the orientation of the eyes, pinnae, and head. These same efferent cells receive multiple sensory inputs, thereby apparently enabling an animal to orient its receptor organs in response to a wide variety of cues. This sensory convergence also provides a system in which motor responses need not be immutably linked to individual stimuli but can vary in reaction to the multitude of stimuli present in the environment at any given moment.}, Author = {Meredith, M A and Stein, B E}, Date-Added = {2010-09-15 15:50:30 -0400}, Date-Modified = {2010-09-15 15:52:24 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology;21 Circuit structure-function;Superior Colliculus;optic tectum;Vision}, Mesh = {Animals; Cats; Electric Stimulation; Motor Activity; Movement; Neurons, Afferent; Neurons, Efferent; Superior Colliculi}, Month = {Feb}, Number = {4687}, Pages = {657-9}, pmid = {3969558}, Pst = {ppublish}, Title = {Descending efferents from the superior colliculus relay integrated multisensory information}, Volume = {227}, Year = {1985}, url = {papers/Meredith_Science1985.pdf}} @article{Carson:2005a, Abstract = {Massive amounts of data are being generated in an effort to represent for the brain the expression of all genes at cellular resolution. Critical to exploiting this effort is the ability to place these data into a common frame of reference. Here we have developed a computational method for annotating gene expression patterns in the context of a digital atlas to facilitate custom user queries and comparisons of this type of data. This procedure has been applied to 200 genes in the postnatal mouse brain. As an illustration of utility, we identify candidate genes that may be related to Parkinson disease by using the expression of a dopamine transporter in the substantia nigra as a search query pattern. In addition, we discover that transcription factor Rorb is down-regulated in the barrelless mutant relative to control mice by quantitative comparison of expression patterns in layer IV somatosensory cortex. The semi-automated annotation method developed here is applicable to a broad spectrum of complex tissues and data modalities.}, Author = {Carson, James P and Ju, Tao and Lu, Hui-Chen and Thaller, Christina and Xu, Mei and Pallas, Sarah L and Crair, Michael C and Warren, Joe and Chiu, Wah and Eichele, Gregor}, Date-Added = {2010-09-15 15:40:30 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS Comput Biol}, Journal-Full = {PLoS computational biology}, Keywords = {10 Development;23 Technique;genetics;Computational Biology}, Mesh = {Anatomy, Artistic; Animals; Brain; Computational Biology; Computer Simulation; Databases, Factual; Gene Expression Profiling; In Situ Hybridization; Medical Illustration; Mice; Transcription, Genetic}, Month = {Sep}, Number = {4}, Pages = {e41}, Pmc = {PMC1215388}, pmid = {16184189}, Pst = {ppublish}, Title = {A digital atlas to characterize the mouse brain transcriptome}, Volume = {1}, Year = {2005}, url = {papers/Carson_PLoSComputBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.0010041}} @article{Andermann:2010, Abstract = {Nearby neurons in mammalian neocortex demonstrate a great diversity of cell types and connectivity patterns. The importance of this diversity for computation is not understood. While extracellular recording studies in visual cortex have provided a particularly rich description of behavioral modulation of neural activity, new methods are needed to dissect the contribution of specific circuit elements in guiding visual perception. Here, we describe a method for three-dimensional cellular imaging of neural activity in the awake mouse visual cortex during active discrimination and passive viewing of visual stimuli. Head-fixed mice demonstrated robust discrimination for many hundred trials per day after initial task acquisition. To record from multiple neurons during operant behavior with single-trial resolution and minimal artifacts, we built a sensitive microscope for two-photon calcium imaging, capable of rapid tracking of neurons in three dimensions. We demonstrate stable recordings of cellular calcium activity during discrimination behavior across hours, days, and weeks, using both synthetic and genetically encoded calcium indicators. When combined with molecular and genetic technologies in mice (e.g., cell-type specific transgenic labeling), this approach allows the identification of neuronal classes in vivo. Physiological measurements from distinct classes of neighboring neurons will enrich our understanding of the coordinated roles of diverse elements of cortical microcircuits in guiding sensory perception and perceptual learning. Further, our method provides a high-throughput, chronic in vivo assay of behavioral influences on cellular activity that is applicable to a wide range of mouse models of neurologic disease.}, Author = {Andermann, Mark L and Kerlin, A M and Reid, R C}, Date-Added = {2010-09-15 15:09:59 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Front Cell Neurosci}, Journal-Full = {Frontiers in cellular neuroscience}, Keywords = {21 Calcium imaging;21 Circuit structure-function;21 Neurophysiology;Visual Cortex;Behavior;23 Technique;optogenetics;frontiers review}, Pages = {3}, Pmc = {PMC2854571}, pmid = {20407583}, Pst = {epublish}, Title = {Chronic cellular imaging of mouse visual cortex during operant behavior and passive viewing}, Volume = {4}, Year = {2010}, url = {papers/Andermann_FrontCellNeurosci2010.pdf}, Bdsk-File-2 = {papers/Andermann_FrontCellNeurosci2010a.pdf}, Bdsk-File-3 = {papers/Andermann_FrontCellNeurosci2010.mov}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncel.2010.00003}} @article{Ecker:2010a, Abstract = {Using the photopigment melanopsin, intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light to drive circadian clock resetting and pupillary constriction. We now report that ipRGCs are more abundant and diverse than previously appreciated, project more widely within the brain, and can support spatial visual perception. A Cre-based melanopsin reporter mouse line revealed at least five subtypes of ipRGCs with distinct morphological and physiological characteristics. Collectively, these cells project beyond the known brain targets of ipRGCs to heavily innervate the superior colliculus and dorsal lateral geniculate nucleus, retinotopically organized nuclei mediating object localization and discrimination. Mice lacking classical rod-cone photoreception, and thus entirely dependent on melanopsin for light detection, were able to discriminate grating stimuli from equiluminant gray and had measurable visual acuity. Thus, nonclassical retinal photoreception occurs within diverse cell types and influences circuits and functions encompassing luminance as well as spatial information.}, Author = {Ecker, Jennifer L and Dumitrescu, Olivia N and Wong, Kwoon Y and Alam, Nazia M and Chen, Shih-Kuo and LeGates, Tara and Renna, Jordan M and Prusky, Glen T and Berson, David M and Hattar, Samer}, Date-Added = {2010-09-15 14:59:29 -0400}, Date-Modified = {2011-09-23 10:08:44 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {melanopsin; retina; Retinal Ganglion Cells; function; Behavior; mouse}, Mesh = {Alkaline Phosphatase; Animals; Circadian Rhythm; Cyclic Nucleotide-Gated Cation Channels; Eye Enucleation; GTP-Binding Protein alpha Subunits; Gene Expression Regulation; Green Fluorescent Proteins; Light; Light Signal Transduction; Maze Learning; Membrane Potentials; Mice; Mice, Knockout; Neural Pathways; Nystagmus, Optokinetic; Patch-Clamp Techniques; Photoreceptor Cells; Retina; Retinal Ganglion Cells; Rod Opsins; Space Perception; Transducin; Vision, Ocular; Visual Acuity; Visual Cortex}, Month = {Jul}, Number = {1}, Pages = {49-60}, Pmc = {PMC2904318}, pmid = {20624591}, Pst = {ppublish}, Title = {Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision}, Volume = {67}, Year = {2010}, url = {papers/Ecker_Neuron2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.05.023}} @article{Grubb:2010, Abstract = {In neurons, the axon initial segment (AIS) is a specialized region near the start of the axon that is the site of action potential initiation. The precise location of the AIS varies across and within different neuronal types, and has been linked to cells' information-processing capabilities; however, the factors determining AIS position in individual neurons remain unknown. Here we show that changes in electrical activity can alter the location of the AIS. In dissociated hippocampal cultures, chronic depolarization with high extracellular potassium moves multiple components of the AIS, including voltage-gated sodium channels, up to 17 mum away from the soma of excitatory neurons. This movement reverses when neurons are returned to non-depolarized conditions, and depends on the activation of T- and/or L-type voltage-gated calcium channels. The AIS also moved distally when we combined long-term LED (light-emitting diode) photostimulation with sparse neuronal expression of the light-activated cation channel channelrhodopsin-2; here, burst patterning of activity was successful where regular stimulation at the same frequency failed. Furthermore, changes in AIS position correlate with alterations in current thresholds for action potential spiking. Our results show that neurons can regulate the position of an entire subcellular structure according to their ongoing levels and patterns of electrical activity. This novel form of activity-dependent plasticity may fine-tune neuronal excitability during development.}, Author = {Grubb, Matthew S and Burrone, Juan}, Date-Added = {2010-09-15 14:59:29 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {Add Keywords}, Mesh = {Action Potentials; Animals; Axons; Calcium Channels, L-Type; Calcium Channels, T-Type; Calcium Signaling; Cells, Cultured; Hippocampus; Humans; Models, Neurological; Neuronal Plasticity; Potassium; Rats; Rats, Sprague-Dawley; Rhodopsin; Sodium Channels}, Month = {Jun}, Number = {7301}, Pages = {1070-4}, pmid = {20543823}, Pst = {ppublish}, Title = {Activity-dependent relocation of the axon initial segment fine-tunes neuronal excitability}, Volume = {465}, Year = {2010}, url = {papers/Grubb_Nature2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature09160}} @article{Strauss:2002, Abstract = {The central complex is one of the most prominent, yet functionally enigmatic structures of the insect brain. Recently, behavioural, neuroanatomical and molecular approaches in Drosophila have joined forces to disclose specific components of higher locomotion control in larvae and adult flies, such as those that guarantee the optimal length and across-body symmetry of strides and an appropriate activity.}, Author = {Strauss, Roland}, Date-Added = {2010-09-15 14:59:29 -0400}, Date-Modified = {2010-09-15 15:00:23 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {Add Keywords}, Mesh = {Animals; Brain; Drosophila; Locomotion; Motor Activity; Orientation}, Month = {Dec}, Number = {6}, Pages = {633-8}, pmid = {12490252}, Pst = {ppublish}, Title = {The central complex and the genetic dissection of locomotor behaviour}, Volume = {12}, Year = {2002}, url = {papers/Strauss_CurrOpinNeurobiol2002.pdf}} @article{Klein:2009, Abstract = {BACKGROUND: A number of adhesion-mediated signaling pathways and cell-cycle events have been identified that regulate cell proliferation, yet studies to date have been unable to determine which of these pathways control mitogenesis in response to physiologically relevant changes in tissue elasticity. In this report, we use hydrogel-based substrata matched to biological tissue stiffness to investigate the effects of matrix elasticity on the cell cycle. RESULTS: We find that physiological tissue stiffness acts as a cell-cycle inhibitor in mammary epithelial cells and vascular smooth muscle cells; subcellular analysis in these cells, mouse embryonic fibroblasts, and osteoblasts shows that cell-cycle control by matrix stiffness is widely conserved. Remarkably, most mitogenic events previously documented as extracellular matrix (ECM)/integrin-dependent proceed normally when matrix stiffness is altered in the range that controls mitogenesis. These include ERK activity, immediate-early gene expression, and cdk inhibitor expression. In contrast, FAK-dependent Rac activation, Rac-dependent cyclin D1 gene induction, and cyclin D1-dependent Rb phosphorylation are strongly inhibited at physiological tissue stiffness and rescued when the matrix is stiffened in vitro. Importantly, the combined use of atomic force microscopy and fluorescence imaging in mice shows that comparable increases in tissue stiffness occur at sites of cell proliferation in vivo. CONCLUSIONS: Matrix remodeling associated with pathogenesis is in itself a positive regulator of the cell cycle through a highly selective effect on integrin-dependent signaling to FAK, Rac, and cyclin D1.}, Author = {Klein, Eric A and Yin, Liqun and Kothapalli, Devashish and Castagnino, Paola and Byfield, Fitzroy J and Xu, Tina and Levental, Ilya and Hawthorne, Elizabeth and Janmey, Paul A and Assoian, Richard K}, Date-Added = {2010-09-15 14:39:56 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {Add Keywords}, Mesh = {Animals; Arteries; Cell Cycle; Cell Proliferation; Cyclin D1; Elasticity; Extracellular Matrix; Focal Adhesion Kinase 1; Hydrogel; Male; Mice; Mice, Inbred C57BL; Phosphorylation; Retinoblastoma Protein; Signal Transduction}, Month = {Sep}, Number = {18}, Pages = {1511-8}, Pmc = {PMC2755619}, pmid = {19765988}, Pst = {ppublish}, Title = {Cell-cycle control by physiological matrix elasticity and in vivo tissue stiffening}, Volume = {19}, Year = {2009}, url = {papers/Klein_CurrBiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2009.07.069}} @article{Asadollahi:2010, Abstract = {The mechanisms by which the brain selects a particular stimulus as the next target for gaze are poorly understood. A cholinergic nucleus in the owl's midbrain exhibits functional properties that suggest its role in bottom-up stimulus selection. Neurons in the nucleus isthmi pars parvocellularis (Ipc) responded to wide ranges of visual and auditory features, but they were not tuned to particular values of those features. Instead, they encoded the relative strengths of stimuli across the entirety of space. Many neurons exhibited switch-like properties, abruptly increasing their responses to a stimulus in their receptive field when it became the strongest stimulus. This information propagates directly to the optic tectum, a structure involved in gaze control and stimulus selection, as periodic (25-50 Hz) bursts of cholinergic activity. The functional properties of Ipc neurons resembled those of a salience map, a core component in computational models for spatial attention and gaze control.}, Author = {Asadollahi, Ali and Mysore, Shreesh P and Knudsen, Eric I}, Date-Added = {2010-09-15 14:39:56 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {Add Keywords}, Mesh = {Animals; Attention; Choice Behavior; Cholinergic Fibers; Conflict (Psychology); Fixation, Ocular; Neural Inhibition; Pedunculopontine Tegmental Nucleus; Photic Stimulation; Strigiformes; Superior Colliculi; Visual Pathways}, Month = {Jul}, Number = {7}, Pages = {889-95}, Pmc = {PMC2893238}, pmid = {20526331}, Pst = {ppublish}, Title = {Stimulus-driven competition in a cholinergic midbrain nucleus}, Volume = {13}, Year = {2010}, url = {papers/Asadollahi_NatNeurosci2010.pdf}, Bdsk-File-2 = {papers/Asadollahi_NatNeurosci2010a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2573}} @article{Saenz:2008, Author = {Saenz, Melissa and Koch, Christof}, Date-Added = {2010-09-15 14:39:56 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {Add Keywords}, Mesh = {Auditory Perception; Brain; Humans; Photic Stimulation; Sensation Disorders}, Month = {Aug}, Number = {15}, Pages = {R650-R651}, pmid = {18682202}, Pst = {ppublish}, Title = {The sound of change: visually-induced auditory synesthesia}, Volume = {18}, Year = {2008}, url = {papers/Saenz_CurrBiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2008.06.014}} @article{Krauzlis:2008a, Abstract = {The neural mechanisms that decide when and where to walk are not well understood. In this issue of Neuron, Felsen and Mainen use an olfactory-guided orienting task to show that the superior colliculus is necessary in rodents for the normal execution of spatial locomotor choices.}, Author = {Krauzlis, Richard J and Lovejoy, Lee P}, Date-Added = {2010-09-15 14:39:56 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Add Keywords}, Mesh = {Animals; Humans; Motor Activity; Orientation; Space Perception; Superior Colliculi; Walking}, Month = {Oct}, Number = {1}, Pages = {7-8}, pmid = {18940583}, Pst = {ppublish}, Title = {Walk this way}, Volume = {60}, Year = {2008}, url = {papers/Krauzlis_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.09.032}} @article{Kastanenka:2010, Abstract = {Spontaneous, highly rhythmic episodes of propagating bursting activity are present early during the development of chick and mouse spinal cords. Acetylcholine, and GABA and glycine, which are both excitatory at this stage, provide the excitatory drive. It was previously shown that a moderate decrease in the frequency of bursting activity, caused by in ovo application of the GABA(A) receptor blocker, picrotoxin, resulted in motoneurons making dorsal-ventral (D-V) pathfinding errors in the limb and in the altered expression of guidance molecules associated with this decision. To distinguish whether the pathfinding errors were caused by perturbation of the normal frequency of bursting activity or interference with GABA(A) receptor signaling, chick embryos were chronically treated in ovo with picrotoxin to block GABA(A) receptors, while light activation by channelrhodopsin-2 was used to restore bursting activity to the control frequency. The restoration of normal patterns of neural activity in the presence of picrotoxin prevented the D-V pathfinding errors in the limb and maintained the normal expression levels of EphA4, EphB1, and polysialic acid on neural cell adhesion molecule, three molecules previously shown to be necessary for this pathfinding choice. These observations demonstrate that developing spinal motor circuits are highly sensitive to the precise frequency and pattern of spontaneous activity, and that any drugs that alter this activity could result in developmental defects.}, Author = {Kastanenka, Ksenia V and Landmesser, Lynn T}, Date-Added = {2010-09-15 14:39:56 -0400}, Date-Modified = {2013-05-31 20:04:59 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 10 Development; 10 circuit formation; Spontaneous activity; optogenetics; frontiers review;activity manipulation;Technique;Spinal Cord;Chick Embryo;structural remodeling;synapse formation;Synaptic Transmission;Synapses;refinement; currOpinRvw}, Mesh = {Action Potentials; Analysis of Variance; Animals; Chick Embryo; GABA Antagonists; Immunohistochemistry; Motor Neurons; Nerve Tissue Proteins; Picrotoxin; Receptors, GABA-A; Rhodopsin; Spinal Cord; Synaptic Transmission}, Month = {Aug}, Number = {31}, Pages = {10575-85}, Pmc = {PMC2934783}, pmid = {20686000}, Pst = {ppublish}, Title = {In vivo activation of channelrhodopsin-2 reveals that normal patterns of spontaneous activity are required for motoneuron guidance and maintenance of guidance molecules}, Volume = {30}, Year = {2010}, url = {papers/Kastanenka_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2773-10.2010}} @article{Ecker:2010, Abstract = {Correlated trial-to-trial variability in the activity of cortical neurons is thought to reflect the functional connectivity of the circuit. Many cortical areas are organized into functional columns, in which neurons are believed to be densely connected and to share common input. Numerous studies report a high degree of correlated variability between nearby cells. We developed chronically implanted multitetrode arrays offering unprecedented recording quality to reexamine this question in the primary visual cortex of awake macaques. We found that even nearby neurons with similar orientation tuning show virtually no correlated variability. Our findings suggest a refinement of current models of cortical microcircuit architecture and function: Either adjacent neurons share only a few percent of their inputs or, alternatively, their activity is actively decorrelated.}, Author = {Ecker, Alexander S and Berens, Philipp and Keliris, Georgios A and Bethge, Matthias and Logothetis, Nikos K and Tolias, Andreas S}, Date-Added = {2010-09-15 14:36:36 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Cortical oscillations;21 Neurophysiology;21 Circuit structure-function;Interneurons}, Mesh = {Action Potentials; Animals; Electrodes, Implanted; Macaca mulatta; Models, Neurological; Nerve Net; Neurons; Photic Stimulation; Synapses; Visual Cortex; Visual Pathways}, Month = {Jan}, Number = {5965}, Pages = {584-7}, pmid = {20110506}, Pst = {ppublish}, Title = {Decorrelated neuronal firing in cortical microcircuits}, Volume = {327}, Year = {2010}, url = {papers/Ecker_Science2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1179867}} @article{Moiseff:2010, Abstract = {Most firefly species (Coleoptera: Lampyridae) use bioluminescent flashes for signaling. In some species, the flashing between males occurs rhythmically and repeatedly (synchronically) with millisecond precision. We studied synchrony's behavioral role in the North American firefly, Photinus carolinus. We placed a female in a virtual environment containing artificial males that flashed at varying degrees of synchrony. Females responded to an average of 82\% of synchronous flashes compared with as few as 3\% of asynchronous flashes. We conclude that one function of flash synchrony is to facilitate a female's ability to recognize her conspecific male's flashing by eliminating potential visual clutter from other flashing males.}, Author = {Moiseff, Andrew and Copeland, Jonathan}, Date-Added = {2010-09-15 14:32:36 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology;20 Networks;synchrony;Computational Biology;Cooperative Behavior;Selection;Game Theory}, Mesh = {Animal Communication; Animals; Behavior, Animal; Female; Fireflies; Light; Male; Periodicity; Species Specificity; Vision, Ocular}, Month = {Jul}, Number = {5988}, Pages = {181}, pmid = {20616271}, Pst = {ppublish}, Title = {Firefly synchrony: a behavioral strategy to minimize visual clutter}, Volume = {329}, Year = {2010}, url = {papers/Moiseff_Science2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1190421}} @article{Akemann:2010, Abstract = {Cortical information processing relies on synaptic interactions between diverse classes of neurons with distinct electrophysiological and connection properties. Uncovering the operational principles of these elaborate circuits requires the probing of electrical activity from selected populations of defined neurons. Here we show that genetically encoded voltage-sensitive fluorescent proteins (VSFPs) provide an optical voltage report from targeted neurons in culture, acute brain slices and living mice. By expressing VSFPs in pyramidal cells of mouse somatosensory cortex, we also demonstrate that these probes can report cortical electrical responses to single sensory stimuli in vivo. These protein-based voltage probes will facilitate the analysis of cortical circuits in genetically defined cell populations and are hence a valuable addition to the optogenetic toolbox.}, Author = {Akemann, Walther and Mutoh, Hiroki and Perron, Am{\'e}lie and Rossier, Jean and Kn{\"o}pfel, Thomas}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Nat Methods}, Journal-Full = {Nature methods}, Keywords = {optogenetics; frontiers review}, Month = {Aug}, Number = {8}, Pages = {643-9}, pmid = {20622860}, Pst = {ppublish}, Title = {Imaging brain electric signals with genetically targeted voltage-sensitive fluorescent proteins}, Volume = {7}, Year = {2010}, url = {papers/Akemann_NatMethods2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1479}} @article{Wallace:2010, Abstract = {Although we know enormous amounts of detailed information about the neurons that make up the cortex, placing this information back into the context of the behaving animal is a serious challenge. The functional cell assembly hypothesis first described by Hebb (The Organization of Behavior; a Neuropsychological Theory. New York: Wiley; 1949) aimed to provide a mechanistic explanation of how groups of neurons, acting together, form a percept. The vast number of neurons potentially involved make testing this hypothesis exceedingly difficult as neither the number nor locations of assembly members are known. Although increasing the number of neurons from which simultaneous recordings are made is of benefit, providing evidence for or against a hypothesis like Hebb's requires more than this. In this review, we aim to outline some recent technical advances, which may light the way in the chase for the functional cell assembly.}, Author = {Wallace, Damian J and Kerr, Jason Nd}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {optical physiology; frontiers review; calcium imaging; Technique;connectivity}, Month = {May}, pmid = {20570133}, Pst = {aheadofprint}, Title = {Chasing the cell assembly}, Year = {2010;c}, url = {papers/Wallace_CurrOpinNeurobiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2010.05.003}} @article{Wickersham:2007, Abstract = {There has never been a wholesale way of identifying neurons that are monosynaptically connected either to some other cell group or, especially, to a single cell. The best available tools, transsynaptic tracers, are unable to distinguish weak direct connections from strong indirect ones. Furthermore, no tracer has proven potent enough to label any connected neurons whatsoever when starting from a single cell. Here we present a transsynaptic tracer that crosses only one synaptic step, unambiguously identifying cells directly presynaptic to the starting population. Based on rabies virus, it is genetically targetable, allows high-level expression of any gene of interest in the synaptically coupled neurons, and robustly labels connections made to single cells. This technology should enable a far more detailed understanding of neural connectivity than has previously been possible.}, Author = {Wickersham, Ian R and Lyon, David C and Barnard, Richard J O and Mori, Takuma and Finke, Stefan and Conzelmann, Karl-Klaus and Young, John A T and Callaway, Edward M}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {Technique;Trans-synaptic;connectivity;connectome;Virus;viral gene transfer;frontiers review}, Mesh = {Action Potentials; Animals; Avian Proteins; Biolistics; Excitatory Postsynaptic Potentials; Gene Deletion; Genetic Complementation Test; Green Fluorescent Proteins; Neural Pathways; Neurons; Organ Culture Techniques; Rabies Vaccines; Rats; Receptors, Virus; Synaptic Transmission; Transfection}, Month = {Mar}, Number = {5}, Pages = {639-47}, Pmc = {PMC2629495}, pmid = {17329205}, Pst = {ppublish}, Title = {Monosynaptic restriction of transsynaptic tracing from single, genetically targeted neurons}, Volume = {53}, Year = {2007}, url = {papers/Wickersham_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.01.033}} @article{Schmid:2010, Abstract = {Injury to the primary visual cortex (V1) leads to the loss of visual experience. Nonetheless, careful testing shows that certain visually guided behaviours can persist even in the absence of visual awareness. The neural circuits supporting this phenomenon, which is often termed blindsight, remain uncertain. Here we demonstrate that the thalamic lateral geniculate nucleus (LGN) has a causal role in V1-independent processing of visual information. By comparing functional magnetic resonance imaging (fMRI) and behavioural measures with and without temporary LGN inactivation, we assessed the contribution of the LGN to visual functions of macaque monkeys (Macaca mulatta) with chronic V1 lesions. Before LGN inactivation, high-contrast stimuli presented to the lesion-affected visual field (scotoma) produced significant V1-independent fMRI activation in the extrastriate cortical areas V2, V3, V4, V5/middle temporal (MT), fundus of the superior temporal sulcus (FST) and lateral intraparietal area (LIP) and the animals correctly located the stimuli in a detection task. However, following reversible inactivation of the LGN in the V1-lesioned hemisphere, fMRI responses and behavioural detection were abolished. These results demonstrate that direct LGN projections to the extrastriate cortex have a critical functional contribution to blindsight. They suggest a viable pathway to mediate fast detection during normal vision.}, Author = {Schmid, Michael C and Mrowka, Sylwia W and Turchi, Janita and Saunders, Richard C and Wilke, Melanie and Peters, Andrew J and Ye, Frank Q and Leopold, David A}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-16 10:43:12 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {blindsight; LGN; visual cortex; Superior Colliculus; pulvinar; fmri; monkey; Macaca; visual system; Sensory Deprivation; structural remodeling; Structure-Activity Relationship; Scotoma; function; Behavior; activity manipulation}, Mesh = {Animals; Female; Geniculate Bodies; Macaca mulatta; Male; Models, Neurological; Photic Stimulation; Visual Cortex; Visual Pathways; Visual Perception}, Month = {Jul}, Number = {7304}, Pages = {373-7}, Pmc = {PMC2904843}, pmid = {20574422}, Pst = {ppublish}, Title = {Blindsight depends on the lateral geniculate nucleus}, Volume = {466}, Year = {2010}, url = {papers/Schmid_Nature2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature09179}} @article{Mysore:2010, Abstract = {Stimulus selection for gaze and spatial attention involves competition among stimuli across sensory modalities and across all of space. We demonstrate that such cross-modal, global competition takes place in the intermediate and deep layers of the optic tectum, a structure known to be involved in gaze control and attention. A variety of either visual or auditory stimuli located anywhere outside of a neuron's receptive field (RF) were shown to suppress or completely eliminate responses to a visual stimulus located inside the RF in nitrous oxide sedated owls. The essential mechanism underlying this stimulus competition is global, divisive inhibition. Unlike the effect of the classical inhibitory surround, which decreases with distance from the RF center and shapes neuronal responses to individual stimuli, global inhibition acts across the entirety of space and modulates responses primarily in the context of multiple stimuli. Whereas the source of this global inhibition is as yet unknown, our data indicate that different networks mediate the classical surround and global inhibition. We hypothesize that this global, cross-modal inhibition, which acts automatically in a bottom-up manner even in sedated animals, is critical to the creation of a map of stimulus salience in the optic tectum.}, Author = {Mysore, Shreesh P and Asadollahi, Ali and Knudsen, Eric I}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Add Keywords}, Mesh = {Animals; Conflict (Psychology); Generalization, Stimulus; Habituation, Psychophysiologic; Inhibition (Psychology); Models, Statistical; Neurons; Normal Distribution; Space Perception; Strigiformes; Superior Colliculi; Visual Perception}, Month = {Feb}, Number = {5}, Pages = {1727-38}, Pmc = {PMC2828882}, pmid = {20130182}, Pst = {ppublish}, Title = {Global inhibition and stimulus competition in the owl optic tectum}, Volume = {30}, Year = {2010}, url = {papers/Mysore_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3740-09.2010}} @article{Berman:2010, Abstract = {The idea of a second visual pathway, in which visual signals travel from brainstem to cortex via the pulvinar thalamus, has had considerable influence as an alternative to the primary geniculo-striate pathway. Existence of this second pathway in primates, however, is not well established. A major question centers on whether the pulvinar acts as a relay, particularly in the path from the superior colliculus (SC) to the motion area in middle temporal cortex (MT). We used physiological microstimulation to identify pulvinar neurons belonging to the path from SC to MT in the macaque. We made three salient observations. First, we identified many neurons in the visual pulvinar that received input from SC or projected to MT, as well as a largely separate set of neurons that received input from MT. Second, and more importantly, we identified a subset of neurons as relay neurons that both received SC input and projected to MT. The identification of these relay neurons demonstrates a continuous functional path from SC to MT through the pulvinar in primates. Third, we histologically localized a subset of SC-MT relay neurons to the subdivision of inferior pulvinar known to project densely to MT but also localized SC-MT relay neurons to an adjacent subdivision. This pattern indicates that the pulvinar pathway is not limited to a single anatomically defined region. These findings bring new perspective to the functional organization of the pulvinar and its role in conveying signals to the cerebral cortex.}, Author = {Berman, Rebecca A and Wurtz, Robert H}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Add Keywords}, Mesh = {Animals; Brain Mapping; Electric Stimulation; Macaca; Male; Neurons; Photic Stimulation; Pulvinar; Superior Colliculi; Temporal Lobe; Time Factors; Visual Pathways}, Month = {May}, Number = {18}, Pages = {6342-54}, Pmc = {PMC2919315}, pmid = {20445060}, Pst = {ppublish}, Title = {Functional identification of a pulvinar path from superior colliculus to cortical area MT}, Volume = {30}, Year = {2010}, url = {papers/Berman_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.6176-09.2010}} @article{Takahashi:2010, Abstract = {Spike synchronization underlies information processing and storage in the brain. But how can neurons synchronize in a noisy network? By exploiting a high-speed (500-2,000 fps) multineuron imaging technique and a large-scale synapse mapping method, we directly compared spontaneous activity patterns and anatomical connectivity in hippocampal CA3 networks ex vivo. As compared to unconnected pairs, synaptically coupled neurons shared more common presynaptic neurons, received more correlated excitatory synaptic inputs, and emitted synchronized spikes with approximately 10(7) times higher probability. Importantly, common presynaptic parents per se synchronized more than unshared upstream neurons. Consistent with this, dynamic-clamp stimulation revealed that common inputs alone could not account for the realistic degree of synchronization unless presynaptic spikes synchronized among common parents. On a macroscopic scale, network activity was coordinated by a power-law scaling of synchronization, which engaged varying sets of densely interwired (thus highly synchronized) neuron groups. Thus, locally coherent activity converges on specific cell assemblies, thereby yielding complex ensemble dynamics. These segmentally synchronized pulse packets may serve as information modules that flow in associatively parallel network channels.}, Author = {Takahashi, Naoya and Sasaki, Takuya and Matsumoto, Wataru and Matsuki, Norio and Ikegaya, Yuji}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-16 10:32:00 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {oscillations; synchrony; hippocampus; network; calcium imaging; microscopy; Technique; 21 Neurophysiology; Theoretical; computation biology}, Mesh = {Action Potentials; Animals; Brain Mapping; CA1 Region, Hippocampal; CA3 Region, Hippocampal; Calcium Signaling; Electrophysiological Phenomena; Excitatory Postsynaptic Potentials; Inhibitory Postsynaptic Potentials; Models, Neurological; Nerve Net; Neurons; Patch-Clamp Techniques; Rats; Rats, Wistar}, Month = {Jun}, Number = {22}, Pages = {10244-9}, Pmc = {PMC2890467}, pmid = {20479225}, Pst = {ppublish}, Title = {Circuit topology for synchronizing neurons in spontaneously active networks}, Volume = {107}, Year = {2010}, url = {papers/Takahashi_ProcNatlAcadSciUSA2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0914594107}} @article{Kanwisher:2010, Abstract = {Is the human mind/brain composed of a set of highly specialized components, each carrying out a specific aspect of human cognition, or is it more of a general-purpose device, in which each component participates in a wide variety of cognitive processes? For nearly two centuries, proponents of specialized organs or modules of the mind and brain--from the phrenologists to Broca to Chomsky and Fodor--have jousted with the proponents of distributed cognitive and neural processing--from Flourens to Lashley to McClelland and Rumelhart. I argue here that research using functional MRI is beginning to answer this long-standing question with new clarity and precision by indicating that at least a few specific aspects of cognition are implemented in brain regions that are highly specialized for that process alone. Cortical regions have been identified that are specialized not only for basic sensory and motor processes but also for the high-level perceptual analysis of faces, places, bodies, visually presented words, and even for the very abstract cognitive function of thinking about another person's thoughts. I further consider the as-yet unanswered questions of how much of the mind and brain are made up of these functionally specialized components and how they arise developmentally.}, Author = {Kanwisher, Nancy}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Add Keywords}, Mesh = {Algorithms; Brain; Brain Mapping; Cognition; Face; Humans; Magnetic Resonance Imaging; Models, Neurological; Nerve Net; Neural Pathways; Perception}, Month = {Jun}, Number = {25}, Pages = {11163-70}, Pmc = {PMC2895137}, pmid = {20484679}, Pst = {ppublish}, Title = {Functional specificity in the human brain: a window into the functional architecture of the mind}, Volume = {107}, Year = {2010}, url = {papers/Kanwisher_ProcNatlAcadSciUSA2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1005062107}} @article{Cohen:2010, Abstract = {Active avoidance of harmful situations seems highly adaptive, but the underlying neural mechanisms are unknown. Rats can effectively use the superior colliculus during active avoidance to detect a salient whisker conditioned stimulus (WCS) that signals an aversive event. Here, we recorded unit and field potential activity in the intermediate layers of the superior colliculus of rats during active avoidance behavior. During the period preceding the onset of the WCS, avoids are associated with a higher firing rate than escapes (unsuccessful avoids), indicating that a prepared superior colliculus is more likely to detect the WCS and lead to an avoid. Moreover, during the WCS, a robust ramping up of the overall firing rate is observed for trials leading to avoids. The firing rate ramping is not caused by shuttling and may serve to drive downstream circuits to avoid. Therefore, a robust neural correlate of active avoidance behavior is found in the superior colliculus, emphasizing its role in the detection of salient sensory signals that require immediate action.}, Author = {Cohen, Jeremy D and Castro-Alamancos, Manuel A}, Date-Added = {2010-09-15 14:30:39 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Add Keywords}, Mesh = {Analysis of Variance; Animals; Avoidance Learning; Behavior, Animal; Conditioning, Classical; Electrophysiology; Escape Reaction; Fourier Analysis; Male; Neural Pathways; Neurons; Rats; Rats, Sprague-Dawley; Signal Processing, Computer-Assisted; Superior Colliculi; Vibrissae}, Month = {Jun}, Number = {25}, Pages = {8502-11}, Pmc = {PMC2905738}, pmid = {20573897}, Pst = {ppublish}, Title = {Neural correlates of active avoidance behavior in superior colliculus}, Volume = {30}, Year = {2010}, url = {papers/Cohen_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1497-10.2010}} @article{Wallace:1989, Abstract = {Transection of the commissure of the superior colliculus restores visual orientation behavior to a cat previously rendered hemianopic by a unilateral visual cortical lesion (the Sprague effect). Using two methods, we asked whether this recovery resulted from the severing of the tectotectal component of the commissure or whether the destruction of some other connection was responsible. First, we transected either the rostral or the caudal one-half of the tectal commissure in hemianopic cats. If destruction of tectotectal fibers is responsible for the Sprague effect, then only rostral transections should produce the recovery since nearly all tectotectal connections lie in the rostral one-half of the commissure. However, rostral cuts failed to produce a recovery, whereas caudal commisurotomies did. Second, ibotenic acid was used to destroy the cells in the superior colliculus contralateral to the cortical lesion. This lesion eliminated the contralateral tectotectal pathway from the contralateral colliculus but left other fibers (originating elsewhere but coursing through the commissure) largely intact. These ibotenic acid lesions failed to produce the recovery; but when the caudal portion of the tectal commissure was subsequently transected in the same animals, the recovery was observed. The results of both experiments support the conclusion that the transection of a nontectotectal component of the commissure of the superior colliculus is responsible for the recovery of visual orientation behavior in a cortically blind cat.}, Author = {Wallace, S F and Rosenquist, A C and Sprague, J M}, Date-Added = {2010-09-15 14:28:03 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Comp Neurol}, Journal-Full = {The Journal of comparative neurology}, Keywords = {21 Neurophysiology;21 Circuit structure-function;21 Neurodegenerative;optic tectum;Superior Colliculus;Vision Disorders;blindsight;sprague effect}, Mesh = {Animals; Cats; Cerebral Cortex; Female; Functional Laterality; Ibotenic Acid; Male; Superior Colliculi; Visual Fields; Visual Pathways; Visual Perception}, Month = {Jun}, Number = {3}, Pages = {429-50}, pmid = {2754044}, Pst = {ppublish}, Title = {Recovery from cortical blindness mediated by destruction of nontectotectal fibers in the commissure of the superior colliculus in the cat}, Volume = {284}, Year = {1989}, url = {papers/Wallace_JCompNeurol1989.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902840309}} @article{Salome:2006, Abstract = {Two-photon scanning microscopy (TPSM) is a powerful tool for imaging deep inside living tissues with sub-cellular resolution. The temporal resolution of TPSM is however strongly limited by the galvanometric mirrors used to steer the laser beam. Fast physiological events can therefore only be followed by scanning repeatedly a single line within the field of view. Because acousto-optic deflectors (AODs) are non-mechanical devices, they allow access at any point within the field of view on a microsecond time scale and are therefore excellent candidates to improve the temporal resolution of TPSM. However, the use of AOD-based scanners with femtosecond pulses raises several technical difficulties. In this paper, we describe an all-digital TPSM setup based on two crossed AODs. It includes in particular an acousto-optic modulator (AOM) placed at 45 degrees with respect to the AODs to pre-compensate for the large spatial distortions of femtosecond pulses occurring in the AODs, in order to optimize the spatial resolution and the fluorescence excitation. Our setup allows recording from freely selectable point-of-interest at high speed (1kHz). By maximizing the time spent on points of interest, random-access TPSM (RA-TPSM) constitutes a promising method for multiunit recordings with millisecond resolution in biological tissues.}, Author = {Salom{\'e}, R and Kremer, Y and Dieudonn{\'e}, S and L{\'e}ger, J-F and Krichevsky, O and Wyart, C and Chatenay, D and Bourdieu, L}, Date-Added = {2010-09-15 14:26:31 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {21 Calcium imaging; 21 Neurophysiology;23 Technique}, Mesh = {Action Potentials; Algorithms; Animals; Calcium Signaling; Cells, Cultured; Diagnostic Imaging; Hippocampus; Lasers; Microscopy, Confocal; Microscopy, Fluorescence; Models, Theoretical; Neurons; Pyramidal Cells; Rats; Signal Processing, Computer-Assisted}, Month = {Jun}, Number = {1-2}, Pages = {161-74}, pmid = {16458361}, Pst = {ppublish}, Title = {Ultrafast random-access scanning in two-photon microscopy using acousto-optic deflectors}, Volume = {154}, Year = {2006}, url = {papers/Salomé_JNeurosciMethods2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2005.12.010}} @article{Teramoto:2010, Abstract = {BACKGROUND: Vision provides the most salient information with regard to stimulus motion, but audition can also provide important cues that affect visual motion perception. Here, we show that sounds containing no motion or positional cues can induce illusory visual motion perception for static visual objects. METHODOLOGY/PRINCIPAL FINDINGS: Two circles placed side by side were presented in alternation producing apparent motion perception and each onset was accompanied by a tone burst of a specific and unique frequency. After exposure to this visual apparent motion with tones for a few minutes, the tones became drivers for illusory motion perception. When the flash onset was synchronized to tones of alternating frequencies, a circle blinking at a fixed location was perceived as lateral motion in the same direction as the previously exposed apparent motion. Furthermore, the effect lasted at least for a few days. The effect was well observed at the retinal position that was previously exposed to apparent motion with tone bursts. CONCLUSIONS/SIGNIFICANCE: The present results indicate that strong association between sound sequence and visual motion is easily formed within a short period and that, after forming the association, sounds are able to trigger visual motion perception for a static visual object.}, Author = {Teramoto, Wataru and Hidaka, Souta and Sugita, Yoichi}, Date-Added = {2010-09-15 14:17:55 -0400}, Date-Modified = {2011-09-12 11:19:14 -0400}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {Add Keywords}, Number = {8}, Pmc = {PMC2924383}, pmid = {20808861}, Pst = {epublish}, Title = {Sounds move a static visual object}, Volume = {5}, Year = {2010}, url = {papers/Teramoto_PLoSOne2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0012255}} @article{Li:2010, Abstract = {BACKGROUND: Catechol-O-methyltransferase (COMT) is a key enzyme responsible for the degradation of dopamine and norepinephrine. COMT activity influences cognitive and emotional states in humans and aggression and drug responses in mice. This study identifies the key sequence variant that leads to differences in Comt mRNA and protein levels among mice, and that modulates synaptic function and pharmacological and behavioral traits. METHODOLOGY/PRINCIPAL FINDINGS: We examined Comt expression in multiple tissues in over 100 diverse strains and several genetic crosses. Differences in expression map back to Comt and are generated by a 230 nt insertion of a B2 short interspersed element (B2 SINE) in the proximal 3' UTR of Comt in C57BL/6J. This transposon introduces a premature polyadenylation signal and creates a short 3' UTR isoform. The B2 SINE is shared by a subset of strains, including C57BL/6J, A/J, BALB/cByJ, and AKR/J, but is absent in others, including DBA/2J, FVB/NJ, SJL/J, and wild subspecies. The short isoform is associated with increased protein expression in prefrontal cortex and hippocampus relative to the longer ancestral isoform. The Comt variant causes downstream differences in the expression of genes involved in synaptic function, and also modulates phenotypes such as dopamine D1 and D2 receptor binding and pharmacological responses to haloperidol. CONCLUSIONS/SIGNIFICANCE: We have precisely defined the B2 SINE as the source of variation in Comt and demonstrated that a transposon in a 3' UTR can alter mRNA isoform use and modulate behavior. The recent fixation of the variant in a subset of strains may have contributed to the rapid divergence of inbred strains.}, Author = {Li, Zhengsheng and Mulligan, Megan K and Wang, Xusheng and Miles, Michael F and Lu, Lu and Williams, Robert W}, Date-Added = {2010-09-15 14:17:55 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {PLoS One}, Journal-Full = {PloS one}, Keywords = {Add Keywords}, Number = {8}, Pmc = {PMC2923157}, pmid = {20808911}, Pst = {epublish}, Title = {A transposon in comt generates mRNA variants and causes widespread expression and behavioral differences among mice}, Volume = {5}, Year = {2010}, url = {papers/Li_PLoSOne2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0012181}} @article{Nakane:2010, Abstract = {It has been known for many decades that nonmammalian vertebrates detect light by deep brain photoreceptors that lie outside the retina and pineal organ to regulate seasonal cycle of reproduction. However, the identity of these photoreceptors has so far remained unclear. Here we report that Opsin 5 is a deep brain photoreceptive molecule in the quail brain. Expression analysis of members of the opsin superfamily identified as Opsin 5 (OPN5; also known as Gpr136, Neuropsin, PGR12, and TMEM13) mRNA in the paraventricular organ (PVO), an area long believed to be capable of phototransduction. Immunohistochemistry identified Opsin 5 in neurons that contact the cerebrospinal fluid in the PVO, as well as fibers extending to the external zone of the median eminence adjacent to the pars tuberalis of the pituitary gland, which translates photoperiodic information into neuroendocrine responses. Heterologous expression of Opsin 5 in Xenopus oocytes resulted in light-dependent activation of membrane currents, the action spectrum of which showed peak sensitivity (lambda(max)) at approximately 420 nm. We also found that short-wavelength light, i.e., between UV-B and blue light, induced photoperiodic responses in eye-patched, pinealectomized quail. Thus, Opsin 5 appears to be one of the deep brain photoreceptive molecules that regulates seasonal reproduction in birds.}, Author = {Nakane, Yusuke and Ikegami, Keisuke and Ono, Hiroko and Yamamoto, Naoyuki and Yoshida, Shosei and Hirunagi, Kanjun and Ebihara, Shizufumi and Kubo, Yoshihiro and Yoshimura, Takashi}, Date-Added = {2010-09-15 14:17:55 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Proc Natl Acad Sci U S A}, Journal-Full = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {Add Keywords}, Month = {Aug}, Number = {34}, Pages = {15264-8}, pmid = {20679218}, Pst = {ppublish}, Title = {A mammalian neural tissue opsin (Opsin 5) is a deep brain photoreceptor in birds}, Volume = {107}, Year = {2010}, url = {papers/Nakane_ProcNatlAcadSciUSA2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1006393107}} @article{Werth:2006, Abstract = {This paper investigates whether and to what extent vision with awareness is still possible in the whole visual field after loss of the occipital lobe of one or both cerebral hemispheres or after hemispherectomy in childhood. The visual functions of four children who suffered from unilateral or bilateral loss of the occipital lobe or who had been hemispherectomized were examined. The results show that even after unilateral loss of the striate and prestriate cortex the extent of the visual field may still be in the normal range. The residual visual functions may be mediated by intact extrastriate areas such as V5 and LO of the damaged cerebral hemisphere. It is also shown that even after complete hemispherectomy in early life the visual field may have a normal extent and that conscious visual perception in the whole visual field may be preserved. In hemispherectomized children, the remaining cerebral hemisphere or neural structures in the midbrain, including the superior colliculi and the praetectum, may be able to mediate these visual functions.}, Author = {Werth, Reinhard}, Date-Added = {2010-09-15 14:17:55 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Eur J Neurosci}, Journal-Full = {The European journal of neuroscience}, Keywords = {currOpinRvw; blindsight; sprague effect; visual cortex; midbrain; superior colliculus; function; human}, Mesh = {Adolescent; Adult; Chi-Square Distribution; Child; Child, Preschool; Electrocardiography; Eye Movements; Female; Functional Laterality; Hemispherectomy; Humans; Infant; Magnetic Resonance Imaging; Male; Nystagmus, Optokinetic; Occipital Lobe; Oxygen; Vision, Ocular; Visual Pathways}, Month = {Nov}, Number = {10}, Pages = {2932-44}, pmid = {17156216}, Pst = {ppublish}, Title = {Visual functions without the occipital lobe or after cerebral hemispherectomy in infancy}, Volume = {24}, Year = {2006}, url = {papers/Werth_EurJNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.05171.x}} @article{Weddell:2004, Abstract = {The Sprague effect is well-established-small tectal lesions restore visual orientation in the hemianopic field of animals with extensive unilateral geniculo-striate lesions. Studies of human midbrain visual functions are rare. This man with a midbrain tumour developed left-neglect through subsequent right frontal damage. Bilateral orientation returned after clear evidence of damage to the superior colliculus contralateral to the cortical lesion (showing the Sprague effect extends to man). Sustained right-neglect developed after probable additional damage to right superior colliculus. The regulation of spatial attention by tecto-pulvinar circuits is discussed, and it is argued that the reduced right tecto-pulvinar activity (consequent to the additional right collicular damage) was offset by over-compensatory increase in thalamic reticular nucleus (TRN) suppression of left pulvinar activity.}, Author = {Weddell, Rodger A}, Date-Added = {2010-09-15 14:17:55 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Brain Cogn}, Journal-Full = {Brain and cognition}, Keywords = {Add Keywords}, Mesh = {Adult; Analysis of Variance; Attention; Brain Neoplasms; Frontal Lobe; Functional Laterality; Glioma; Humans; Male; Middle Aged; Neuropsychological Tests; Perceptual Disorders; Reaction Time; Recovery of Function; Space Perception; Superior Colliculi; Visual Pathways}, Month = {Aug}, Number = {3}, Pages = {497-506}, pmid = {15223196}, Pst = {ppublish}, Title = {Subcortical modulation of spatial attention including evidence that the Sprague effect extends to man}, Volume = {55}, Year = {2004}, url = {papers/Weddell_BrainCogn2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.bandc.2004.02.075}} @article{Ptito:2007, Abstract = {Blindsight is a visual phenomenon whereby hemianopic patients are able to process visual information in their blind visual field without awareness. Previous research demonstrating the existence of blindsight in hemianopic patients has been criticized for the nature of the paradigms used, for the presence of methodological artifacts, and for the possibility that spared islands of visual cortex may have sustained the phenomenon because the patients generally had small circumscribed lesions. To respond to these criticisms, the authors have been investigating for several years now residual visual abilities in the blind field of hemispherectomized patients in whom a whole cerebral hemisphere has been removed or disconnected from the rest of the brain. These patients have offered a unique opportunity to establish the existence of blindsight and to investigate its underlying neuronal mechanisms because in these cases, spared islands of visual cortex cannot be evoked to explain the presence of visual abilities in the blind field. In addition, the authors have been using precise behavioral paradigms, strict control for potential methodological artifacts such as light scatter, fixation, criterion effects, and macular sparing, and they have utilized new neuroimaging techniques such as diffusion tensor imaging tractography to enhance their understanding of the phenomenon. The following article is a review of their research on the involvement of the superior colliculi in blindsight in hemispherectomized patients. .}, Author = {Ptito, Alain and Leh, Sandra E}, Date-Added = {2010-09-15 14:17:55 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Neuroscientist}, Journal-Full = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, Keywords = {Add Keywords}, Mesh = {Awareness; Diffusion Magnetic Resonance Imaging; Discrimination (Psychology); Hemianopsia; Hemispherectomy; Humans; Magnetic Resonance Imaging; Motion Perception; Postoperative Complications; Visual Fields; Visual Perception}, Month = {Oct}, Number = {5}, Pages = {506-18}, pmid = {17901259}, Pst = {ppublish}, Title = {Neural substrates of blindsight after hemispherectomy}, Volume = {13}, Year = {2007}, url = {papers/Ptito_Neuroscientist2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1177/1073858407300598}} @article{Chen:2010, Abstract = {Mouse Hoxb8 mutants show unexpected behavior manifested by compulsive grooming and hair removal, similar to behavior in humans with the obsessive-compulsive disorder spectrum disorder trichotillomania. As Hox gene disruption often has pleiotropic effects, the root cause of this behavioral deficit was unclear. Here we report that, in the brain, Hoxb8 cell lineage exclusively labels bone marrow-derived microglia. Furthermore, transplantation of wild-type bone marrow into Hoxb8 mutant mice rescues their pathological phenotype. It has been suggested that the grooming dysfunction results from a nociceptive defect, also exhibited by Hoxb8 mutant mice. However, bone marrow transplant experiments and cell type-specific disruption of Hoxb8 reveal that these two phenotypes are separable, with the grooming phenotype derived from the hematopoietic lineage and the sensory defect derived from the spinal cord cells. Immunological dysfunctions have been associated with neuropsychiatric disorders, but the causative relationships are unclear. In this mouse, a distinct compulsive behavioral disorder is associated with mutant microglia.}, Author = {Chen, Shau-Kwaun and Tvrdik, Petr and Peden, Erik and Cho, Scott and Wu, Sen and Spangrude, Gerald and Capecchi, Mario R}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Cell}, Journal-Full = {Cell}, Keywords = {Grants; ideas; 11 Glia; 14 Immune; Microglia; neurological disorder}, Mesh = {Animals; B-Lymphocytes; Behavior, Animal; Bone Marrow Transplantation; Brain; Grooming; Homeodomain Proteins; Humans; Mice; Microglia; Obsessive-Compulsive Disorder; Spinal Cord; T-Lymphocytes}, Month = {May}, Number = {5}, Pages = {775-85}, Pmc = {PMC2894573}, pmid = {20510925}, Pst = {ppublish}, Title = {Hematopoietic origin of pathological grooming in Hoxb8 mutant mice}, Volume = {141}, Year = {2010}, url = {papers/Chen_Cell2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2010.03.055}} @article{Kerlin:2010, Abstract = {Different subtypes of GABAergic neurons in sensory cortex exhibit diverse morphology, histochemical markers, and patterns of connectivity. These subtypes likely play distinct roles in cortical function, but their in vivo response properties remain unclear. We used in vivo calcium imaging, combined with immunohistochemical and genetic labels, to record visual responses in excitatory neurons and up to three distinct subtypes of GABAergic neurons (immunoreactive for parvalbumin, somatostatin, or vasoactive intestinal peptide) in layer 2/3 of mouse visual cortex. Excitatory neurons had sharp response selectivity for stimulus orientation and spatial frequency, while all GABAergic subtypes had broader selectivity. Further, bias in the responses of GABAergic neurons toward particular orientations or spatial frequencies tended to reflect net biases of the surrounding neurons. These results suggest that the sensory responses of layer 2/3 GABAergic neurons reflect the pooled activity of the surrounding population-a principle that may generalize across species and sensory modalities.}, Author = {Kerlin, Aaron M and Andermann, Mark L and Berezovskii, Vladimir K and Reid, R Clay}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Calcium imaging; 21 Circuit structure-function;21 Neurophysiology; Interneurons}, Month = {Sep}, Number = {5}, Pages = {858-71}, pmid = {20826316}, Pst = {ppublish}, Title = {Broadly tuned response properties of diverse inhibitory neuron subtypes in mouse visual cortex}, Volume = {67}, Year = {2010}, url = {papers/Kerlin_Neuron2010.pdf}, Bdsk-File-2 = {papers/Kerlin_Neuron2010a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2010.08.002}} @article{Wang:2010, Abstract = {We investigated the specificity of cyan fluorescent protein (CFP) expression in retinal ganglion cells (RGCs) of the transgenic Thy1-CFP (B6.Cg-Tg(Thy1-CFP)23Jrs/J) mouse line, and the characteristics of these cells after optic nerve injury. RGCs of adult Thy1-CFP mice were retrogradely labeled with fluorochrome (2\% fluorogold [FG]) from the superior colliculi (SC). Animals were sacrificed 7 days after RGC labeling. Retinas were fixed and whole-mounted. CFP and FG-positive cells were visualized and imaged separately. Cells positive for CFP, FG, or co-labeled were counted. In another group of animals, the left optic nerves were transected 7 days after FG labeling. They were sacrificed 7 or 21 days after transection. The retinas were whole-mounted and the characteristics of CFP-expressing cells examined. CFP-expressing cells were distributed evenly throughout the retinas of Thy1-CFP mice. The average densities of CFP and FG-positive cells in the retina were 2778+/-216 and 3230+/-157 cells/mm(2), respectively. 93.2+/-1.6\% of CFP-expressing cells were also labeled with FG. However, only 79.9+/-2.5\% of FG-labeled RGCs expressed CFP. The number of CFP-expressing cells decreased dramatically after transection. Cells with spindle shape, immunohistochemically identified as microglia, were seen in the retina with CFP expression at both 7 and 21 days after optic nerve transection. In retinas of Thy1-CFP mice, CFP is expressed by the large majority of RGCs, but not exclusively by RGCs. CFP is internalized by phagocytosing cells after injury to RGCs.}, Author = {Wang, Xu and Archibald, Michele L and Stevens, Kelly and Baldridge, William H and Chauhan, Balwantray C}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Neurosci Lett}, Journal-Full = {Neuroscience letters}, Keywords = {21 Neurodegenerative; retina; Vision Disorders}, Mesh = {Animals; Antigens, Thy-1; Green Fluorescent Proteins; Immunohistochemistry; Mice; Mice, Transgenic; Microglia; Optic Nerve Injuries; Promoter Regions, Genetic; Retina; Retinal Ganglion Cells}, Month = {Jan}, Number = {2}, Pages = {110-4}, pmid = {19879331}, Pst = {ppublish}, Title = {Cyan fluorescent protein (CFP) expressing cells in the retina of Thy1-CFP transgenic mice before and after optic nerve injury}, Volume = {468}, Year = {2010}, url = {papers/Wang_NeurosciLett2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2009.10.077}} @article{Szokol:2009, Abstract = {Descending inputs to spinal cord neurons in mammals have previously been characterized functionally using microelectrode recording of single neurons, a technique with high spatial and temporal resolution but low yield. Consequently our knowledge about the functional connections between the brain and the spinal cord has been accumulating at a very low pace. Here we describe a high throughput optical recording approach in an ex vivo brainstem-spinal cord preparation of the neonatal mouse that permits screening many spinal neurons simultaneously for synaptic inputs from descending axons. The fluorescent calcium indicator calcium green dextran amine was loaded retrogradely into specific spinal neuron populations, including motoneurons (MNs) of the medial and lateral motor columns and two populations of interneurons with descending axons (dINs) in the ventral funiculus. Focal electrical stimulation of brainstem neuron populations with descending axons generated synaptic responses revealed by transient increases in intracellular calcium concentration in all four populations of spinal neurons. The resultant fluorescence signals could be readily visualized in individual MNs directly through the ventral white matter. In the more deeply located dINs, responses could be readily visualized in individual neurons from the surface of an oblique cut through the spinal cord. The rapid optical investigation of functional connections between brainstem descending neurons and various populations of spinal neurons in the living mammalian preparation should help uncover some of the key features of supraspinal sensory and motor control and provide a valuable tool for examining the re-innervation of spinal neurons by descending axons after spinal cord regeneration.}, Author = {Szokol, Karolina and Perreault, Marie-Claude}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {21 Neurophysiology; 21 Circuit structure-function;Motor Activity; Locomotion/physiology; 21 Calcium imaging}, Mesh = {Animals; Animals, Newborn; Axons; Brain Stem; Calcium; Efferent Pathways; Electric Stimulation; Fluorescent Dyes; Indicators and Reagents; Interneurons; Mice; Mice, Inbred ICR; Microscopy, Fluorescence; Microscopy, Video; Motor Neurons; Neurons; Optics and Photonics; Organ Culture Techniques; Organic Chemicals; Reticular Formation; Spinal Cord; Staining and Labeling; Synaptic Transmission}, Month = {May}, Number = {1}, Pages = {1-8}, pmid = {19427523}, Pst = {ppublish}, Title = {Imaging synaptically mediated responses produced by brainstem inputs onto identified spinal neurons in the neonatal mouse}, Volume = {180}, Year = {2009}, url = {papers/Szokol_JNeurosciMethods2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2009.01.018}} @article{Lillis:2008, Abstract = {We describe a simple two-photon fluorescence imaging strategy, called targeted path scanning (TPS), to monitor the dynamics of spatially extended neuronal networks with high spatiotemporal resolution. Our strategy combines the advantages of mirror-based scanning, minimized dead time, ease of implementation, and compatibility with high-resolution low-magnification objectives. To demonstrate the performance of TPS, we monitor the calcium dynamics distributed across an entire juvenile rat hippocampus (>1.5mm), at scan rates of 100 Hz, with single cell resolution and single action potential sensitivity. Our strategy for fast, efficient two-photon microscopy over spatially extended regions provides a particularly attractive solution for monitoring neuronal population activity in thick tissue, without sacrificing the signal-to-noise ratio or high spatial resolution associated with standard two-photon microscopy. Finally, we provide the code to make our technique generally available.}, Author = {Lillis, Kyle P and Eng, Alfred and White, John A and Mertz, Jerome}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {21 Calcium imaging;21 Neurophysiology; 23 Technique}, Mesh = {Animals; Calcium; Calcium Signaling; Fluorescent Dyes; Hippocampus; Image Cytometry; Imaging, Three-Dimensional; Membrane Potentials; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton; Nerve Net; Neural Pathways; Neurons; Optics and Photonics; Organ Culture Techniques; Photons; Rats; Rats, Long-Evans; Software; Time Factors}, Month = {Jul}, Number = {2}, Pages = {178-84}, Pmc = {PMC2582024}, pmid = {18539336}, Pst = {ppublish}, Title = {Two-photon imaging of spatially extended neuronal network dynamics with high temporal resolution}, Volume = {172}, Year = {2008}, url = {papers/Lillis_JNeurosciMethods2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2008.04.024}} @article{Shew:2010, Abstract = {A complete understanding of how brain circuits function will require measurement techniques which monitor large-scale network activity simultaneously with the activity of local neural populations at a small scale. Here we present a useful step towards achieving this aim: simultaneous two-photon calcium imaging and multi-electrode array (MEA) recordings. The primary challenge of this method is removing an electrical artifact from the MEA signals that is caused by the imaging laser. Here we show that artifact removal can be achieved with a simple filtering scheme. As a demonstration of this technique we compare large-scale local field potential signals to single-neuron activity in a small-scale group of cells recorded from rat acute slices under two conditions: suppressed vs. intact inhibitory interactions between neurons.}, Author = {Shew, Woodrow L and Bellay, Timothy and Plenz, Dietmar}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {J Neurosci Methods}, Journal-Full = {Journal of neuroscience methods}, Keywords = {21 Calcium imaging; 21 Circuit structure-function;21 Neurophysiology; Interneurons; 23 Technique}, Month = {Sep}, Number = {1}, Pages = {75-82}, Pmc = {PMC2934901}, pmid = {20659501}, Pst = {ppublish}, Title = {Simultaneous multi-electrode array recording and two-photon calcium imaging of neural activity}, Volume = {192}, Year = {2010}, url = {papers/Shew_JNeurosciMethods2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2010.07.023}} @article{Lee:2006b, Abstract = {Standard economic theories conceive homo economicus as a rational decision maker capable of maximizing utility. In reality, however, people tend to approximate optimal decision-making strategies through a collection of heuristic routines. Some of these routines are driven by emotional processes, and others are adjusted iteratively through experience. In addition, routines specialized for social decision making, such as inference about the mental states of other decision makers, might share their origins and neural mechanisms with the ability to simulate or imagine outcomes expected from alternative actions that an individual can take. A recent surge of collaborations across economics, psychology and neuroscience has provided new insights into how such multiple elements of decision making interact in the brain.}, Author = {Lee, Daeyeol}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Curr Opin Neurobiol}, Journal-Full = {Current opinion in neurobiology}, Keywords = {20 Networks; 21 Circuit structure-function; 21 Neurophysiology; Game Theory; Behavior; Cooperative Behavior}, Mesh = {Animals; Brain; Cognition; Decision Making; Economics; Emotions; Humans; Learning; Models, Neurological; Nerve Net; Reward; Social Behavior}, Month = {Apr}, Number = {2}, Pages = {191-8}, pmid = {16531040}, Pst = {ppublish}, Title = {Neural basis of quasi-rational decision making}, Volume = {16}, Year = {2006}, url = {papers/Lee_CurrOpinNeurobiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2006.02.001}} @article{Richards:2010, Abstract = {During the development of sensory systems, receptive fields are modified by stimuli in the environment. This is thought to rely on learning algorithms that are sensitive to correlations in spike timing between cells, but the manner in which developing circuits selectively exploit correlations that are related to sensory inputs is unknown. We recorded from neurons in the developing optic tectum of Xenopus laevis and found that repeated presentation of moving visual stimuli induced receptive field changes that reflected the properties of the stimuli and that this form of learning was disrupted when GABAergic transmission was blocked. Consistent with a role for spike timing-dependent mechanisms, GABA blockade altered spike-timing patterns in the tectum and increased correlations between cells that would affect plasticity at intratectal synapses. This is a previously unknown role for GABAergic signals in development and highlights the importance of regulating the statistics of spiking activity for learning.}, Author = {Richards, Blake A and Voss, Oliver P and Akerman, Colin J}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Circuit structure-function;21 Neurophysiology; Interneurons; 21 Activity-development; 10 circuit formation; optic tectum; Vision; Superior Colliculus}, Month = {Sep}, Number = {9}, Pages = {1098-106}, pmid = {20694002}, Pst = {ppublish}, Title = {GABAergic circuits control stimulus-instructed receptive field development in the optic tectum}, Volume = {13}, Year = {2010}, url = {papers/Richards_NatNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2612}} @article{Smith:2010, Abstract = {Visual cortex shows smooth retinotopic organization on the macroscopic scale, but it is unknown how receptive fields are organized at the level of neighboring neurons. This information is crucial for discriminating among models of visual cortex. We used in vivo two-photon calcium imaging to independently map ON and OFF receptive field subregions of local populations of layer 2/3 neurons in mouse visual cortex. Receptive field subregions were often precisely shared among neighboring neurons. Furthermore, large subregions seem to be assembled from multiple smaller, non-overlapping subregions of other neurons in the same local population. These experiments provide, to our knowledge, the first characterization of the diversity of receptive fields in a dense local network of visual cortex and reveal elementary units of receptive field organization. Our results suggest that a limited pool of afferent receptive fields is available to a local population of neurons and reveal new organizational principles for the neural circuitry of the mouse visual cortex.}, Author = {Smith, Spencer L and H{\"a}usser, Michael}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Nat Neurosci}, Journal-Full = {Nature neuroscience}, Keywords = {21 Calcium imaging; 21 Circuit structure-function;21 Neurophysiology; vision; Visual Cortex/*physiology}, Month = {Sep}, Number = {9}, Pages = {1144-9}, pmid = {20711183}, Pst = {ppublish}, Title = {Parallel processing of visual space by neighboring neurons in mouse visual cortex}, Volume = {13}, Year = {2010}, url = {papers/Smith_NatNeurosci2010.pdf}, Bdsk-File-2 = {papers/Smith_NatNeurosci2010a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2620}} @article{Jahn:2008, Abstract = {An erect posture with bipedal locomotion is a characteristic feature of humans compared to other mammals. Most of our knowledge about the hierarchical network of supraspinal locomotor centers derives from animal experiments, mainly in the cat. We posed the question of whether evolutionary transition from quadrupedal to bipedal locomotion--with associated change of foreleg function--caused reorganization of these supraspinal locomotor centers. Using functional magnetic resonance imaging, we identified separate and distinct cerebellar and brainstem BOLD signal increases related to posture and gait during mental imagery of standing, walking, and running in healthy volunteers (n=26). Comparison with the locomotion centers in the cat showed that these activations include the pacemakers for gait initiation and speed regulation in the interfastigial cerebellum and bilateral midbrain tegmentum (cerebellar and mesencephalic locomotor regions), their descending target regions in the pontine reticular formation, and the rhythm generators in the cerebellar vermis and paravermal cortex. Moreover, during mental imagery of stance, a BOLD signal increase was observed in the dorsal pons, reflecting an activation of the dorsal tegmental field, a locomotion-suppressing site in the cat. These results support the view that the organization of supraspinal locomotor centers was preserved during the transition to bipedal locomotion. The clinical relevance of these centers has so far been largely neglected. However, Parkinson's disease, for example, is associated with reduced cell counts in the pedunculopontine nucleus, a part of the mesencephalic locomotor region. This association suggests that deep brain stimulation of locomotion centers may provide new therapeutic approaches for common gait disorders.}, Author = {Jahn, Klaus and Deutschl{\"a}nder, Angela and Stephan, Thomas and Kalla, Roger and Wiesmann, Martin and Strupp, Michael and Brandt, Thomas}, Date-Added = {2010-09-15 13:48:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Neuroimage}, Journal-Full = {NeuroImage}, Keywords = {21 Neurophysiology; 21 Circuit structure-function; Superior Colliculus; optic tectum; fmri; Motor Activity; Locomotion/physiology}, Mesh = {Adult; Animals; Brain Stem; Cats; Cerebellum; Data Interpretation, Statistical; Female; Humans; Imagination; Locomotion; Magnetic Resonance Imaging; Male; Middle Aged; Nerve Net; Oxygen; Posture; Running}, Month = {Jan}, Number = {2}, Pages = {786-92}, pmid = {18029199}, Pst = {ppublish}, Title = {Imaging human supraspinal locomotor centers in brainstem and cerebellum}, Volume = {39}, Year = {2008}, url = {papers/Jahn_Neuroimage2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2007.09.047}} @article{Okasha:2010, Author = {Okasha, Samir}, Date-Added = {2010-09-15 13:34:59 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {20 Networks; Selection; Cooperative Behavior; Game Theory; ideas}, Mesh = {Animals; Evolution; Genetics; History, 19th Century; History, 20th Century; Humans; Models, Genetic; Selection, Genetic}, Month = {Apr}, Number = {7}, Pages = {R306-7}, pmid = {20392416}, Pst = {ppublish}, Title = {Levels of selection}, Volume = {20}, Year = {2010}, url = {papers/Okasha_CurrBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2010.01.025}} @article{Foster:2010, Abstract = {In the epic race for the egg, sperm have evolved cooperative teams that swim together. New research shows that some do even more: sperm seek out and swim with their relatives.}, Author = {Foster, Kevin R and Pizzari, Tommaso}, Date-Added = {2010-09-15 13:32:50 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Curr Biol}, Journal-Full = {Current biology : CB}, Keywords = {20 Networks; Selection; Cooperative Behavior; Game Theory; ideas}, Mesh = {Animals; Cell Communication; Female; Male; Models, Biological; Peromyscus; Selection, Genetic; Sperm-Ovum Interactions; Spermatozoa}, Month = {Apr}, Number = {7}, Pages = {R314-6}, pmid = {20392420}, Pst = {ppublish}, Title = {Cooperation: the secret society of sperm}, Volume = {20}, Year = {2010}, url = {papers/Foster_CurrBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2010.02.015}} @article{Emerman:2010, Author = {Emerman, Michael and Malik, Harmit S}, Date-Added = {2010-09-15 13:30:23 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {PLoS Biol}, Journal-Full = {PLoS biology}, Keywords = {Grants; ideas; 15 ERVs retroelements}, Mesh = {Evolution; Humans; Paleontology; Viruses}, Month = {Feb}, Number = {2}, Pages = {e1000301}, Pmc = {PMC2817711}, pmid = {20161719}, Pst = {epublish}, Title = {Paleovirology--modern consequences of ancient viruses}, Volume = {8}, Year = {2010}, url = {papers/Emerman_PLoSBiol2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.1000301}} @article{Murchison:2010, Abstract = {The Tasmanian devil, a marsupial carnivore, is endangered because of the emergence of a transmissible cancer known as devil facial tumor disease (DFTD). This fatal cancer is clonally derived and is an allograft transmitted between devils by biting. We performed a large-scale genetic analysis of DFTD with microsatellite genotyping, a mitochondrial genome analysis, and deep sequencing of the DFTD transcriptome and microRNAs. These studies confirm that DFTD is a monophyletic clonally transmissible tumor and suggest that the disease is of Schwann cell origin. On the basis of these results, we have generated a diagnostic marker for DFTD and identify a suite of genes relevant to DFTD pathology and transmission. We provide a genomic data set for the Tasmanian devil that is applicable to cancer diagnosis, disease evolution, and conservation biology.}, Author = {Murchison, Elizabeth P and Tovar, Cesar and Hsu, Arthur and Bender, Hannah S and Kheradpour, Pouya and Rebbeck, Clare A and Obendorf, David and Conlan, Carly and Bahlo, Melanie and Blizzard, Catherine A and Pyecroft, Stephen and Kreiss, Alexandre and Kellis, Manolis and Stark, Alexander and Harkins, Timothy T and Marshall Graves, Jennifer A and Woods, Gregory M and Hannon, Gregory J and Papenfuss, Anthony T}, Date-Added = {2010-09-15 13:28:32 -0400}, Date-Modified = {2011-09-13 09:45:17 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {Grants; ideas;; microRNAs; development}, Mesh = {Animals; Bites and Stings; Cell Differentiation; Facial Neoplasms; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Genome, Mitochondrial; Genotype; Marsupialia; Membrane Proteins; MicroRNAs; Microsatellite Repeats; Myelin Basic Proteins; Nerve Sheath Neoplasms; Schwann Cells; Sequence Analysis, DNA; Tumor Markers, Biological}, Month = {Jan}, Number = {5961}, Pages = {84-7}, pmid = {20044575}, Pst = {ppublish}, Title = {The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer}, Volume = {327}, Year = {2010}, url = {papers/Murchison_Science2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1180616}} @article{Engel:1991, Abstract = {Neurons in area 17 of cat visual cortex display oscillatory responses that can synchronize across spatially separate columns in a stimulus-specific way. Response synchronization has now been shown to occur also between neurons in area 17 of the right and left cerebral hemispheres. This synchronization was abolished by section of the corpus callosum. Thus, the response synchronization is mediated by corticocortical connections. These data are compatible with the hypothesis that temporal synchrony of neuronal discharges serves to bind features within and between the visual hemifields.}, Author = {Engel, A K and K{\"o}nig, P and Kreiter, A K and Singer, W}, Date-Added = {2010-09-15 13:17:05 -0400}, Date-Modified = {2010-09-15 13:17:57 -0400}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Mesh = {Animals; Cats; Corpus Callosum; Functional Laterality; Neurons; Oscillometry; Time Factors; Visual Cortex; Visual Fields}, Month = {May}, Number = {5010}, Pages = {1177-9}, pmid = {2031188}, Pst = {ppublish}, Title = {Interhemispheric synchronization of oscillatory neuronal responses in cat visual cortex}, Volume = {252}, Year = {1991}, url = {papers/Engel_Science1991.pdf}} @article{Rosenbaum:2010, Abstract = {Correlations between spike trains can strongly modulate neuronal activity and affect the ability of neurons to encode information. Neurons integrate inputs from thousands of afferents. Similarly, a number of experimental techniques are designed to record pooled cell activity. We review and generalize a number of previous results that show how correlations between cells in a population can be amplified and distorted in signals that reflect their collective activity. The structure of the underlying neuronal response can significantly impact correlations between such pooled signals. Therefore care needs to be taken when interpreting pooled recordings, or modeling networks of cells that receive inputs from large presynaptic populations. We also show that the frequently observed runaway synchrony in feedforward chains is primarily due to the pooling of correlated inputs.}, Author = {Rosenbaum, Robert J and Trousdale, James and Josi{\'c}, Kresimir}, Date-Added = {2010-09-15 12:49:59 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Front Comput Neurosci}, Journal-Full = {Frontiers in computational neuroscience}, Keywords = {21 Neurophysiology; Models; Computational Biology}, Pages = {9}, Pmc = {PMC2870944}, pmid = {20485451}, Pst = {epublish}, Title = {Pooling and correlated neural activity}, Volume = {4}, Year = {2010}, url = {papers/Rosenbaum_FrontComputNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.3389/fncom.2010.00009}} @article{Colonnese:2010, Abstract = {A primary feature of the preterm infant electroencephalogram is the presence of large infra-slow potentials containing rapid oscillations called slow activity transients (SATs). Such activity has not been described in animal models, and their generative mechanisms are unknown. Here we use direct-current and multisite extracellular, as well as whole-cell, recording in vivo to demonstrate the existence of regularly repeating SATs in the visual cortex of infant rats before eye opening. Present only in absence of anesthesia, SATs at postnatal day 10-11 were identifiable as a separate group of long-duration (approximately 10 s) events that consisted of large (>1 mV) negative local-field potentials produced by the summation of multiple bursts of rapid oscillatory activity (15-30 Hz). SATs synchronized the vast majority of neuronal activity (87\%) in the visual cortex before eye opening. Enucleation eliminated SATs, and their duration, interevent interval, and sub-burst structure matched those of phase III retinal waves recorded in vitro. Retinal waves, however, lacked rapid oscillations, suggesting that they arise centrally. Multielectrode recordings showed that SATs spread horizontally in cortex and synchronize activity at coactive locales via the rapid oscillations. SATs were clearly different from ongoing cortical activity, which was observable as a separate class of short bursts from postnatal day 9. Together, our data suggest that, in vivo, early cortical activity is primarily determined by peripheral inputs-retinal waves in visual cortex-that provide excitatory input, and by thalamocortical circuitry, which transforms this input to beta oscillations. We propose that the synchronous oscillations of SATs participate in the formation of visual circuitry.}, Author = {Colonnese, Matthew T and Khazipov, Rustem}, Date-Added = {2010-09-15 11:35:54 -0400}, Date-Modified = {2013-05-28 21:00:04 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology; Spontaneous activity; currOpinRvw}, Mesh = {Action Potentials; Age Factors; Anesthetics; Animals; Animals, Newborn; Biological Clocks; Cortical Spreading Depression; Dose-Response Relationship, Drug; Electroencephalography; Functional Laterality; Isoflurane; Neural Inhibition; Patch-Clamp Techniques; Rats; Rats, Long-Evans; Retina; Sensory Deprivation; Spectrum Analysis; Statistics, Nonparametric; Urethane; Visual Cortex; Visual Pathways}, Month = {Mar}, Number = {12}, Pages = {4325-37}, pmid = {20335468}, Pst = {ppublish}, Title = {"Slow activity transients" in infant rat visual cortex: a spreading synchronous oscillation patterned by retinal waves}, Volume = {30}, Year = {2010}, url = {papers/Colonnese_JNeurosci2010.pdf}, Bdsk-File-2 = {papers/Colonnese_JNeurosci2010a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4995-09.2010}} @article{Mohns:2010, Abstract = {We recently reported that the majority of hippocampal neurons in newborn rats increase their activity in association with myoclonic twitches, which are indicative of active sleep. Because spindle bursts in the developing somatosensory neocortex occur in response to sensory feedback from myoclonic twitching, we hypothesized that the state-dependent activity of the newborn hippocampus arises from sensory feedback that sequentially activates the neocortex and then hippocampus, constituting an early form of neocortical-hippocampal communication. Here, in unanesthetized 5- to 6-d-old rats, we test this hypothesis by recording simultaneously from forelimb and barrel regions of somatosensory neocortex and dorsal hippocampus during periods of spontaneous sleep and wakefulness and in response to peripheral stimulation. Myoclonic twitches were consistently followed by neocortical spindle bursts, which were in turn consistently followed by bursts of hippocampal unit activity; moreover, spindle burst power was positively correlated with hippocampal unit activity. In addition, exogenous stimulation consistently evoked this neocortical-to-hippocampal sequence of activation. Finally, parahippocampal lesions that disrupted functional connections between the neocortex and hippocampus effectively disrupted the transmission of both spontaneous and evoked neocortical activity to the hippocampus. These findings suggest that sleep-related motor activity contributes to the development of neocortical and hippocampal circuits and provides a foundation on which coordinated activity between these two forebrain structures develops.}, Author = {Mohns, Ethan J and Blumberg, Mark S}, Date-Added = {2010-03-12 16:54:59 -0500}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology; Spontaneous activity}, Month = {Mar}, Number = {9}, Pages = {3438-49}, pmid = {20203203}, Pst = {ppublish}, Title = {Neocortical Activation of the Hippocampus during Sleep in Infant Rats}, Volume = {30}, Year = {2010}, url = {papers/Mohns_JNeurosci2010.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4832-09.2010}} @article{Stein:1984, Author = {Stein, B E}, Date-Added = {2010-02-23 15:10:42 -0500}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Annu Rev Neurosci}, Journal-Full = {Annual review of neuroscience}, Mesh = {Animals; Auditory Cortex; Cats; Cerebral Cortex; Eye Movements; Motor Cortex; Movement; Neural Pathways; Neurons; Retina; Somatosensory Cortex; Strabismus; Superior Colliculi; Vision, Ocular; Visual Cortex; Visual Fields; Visual Perception}, Pages = {95-125}, pmid = {6370084}, Pst = {ppublish}, Title = {Development of the superior colliculus}, Volume = {7}, Year = {1984}, url = {papers/Stein_AnnuRevNeurosci1984.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.ne.07.030184.000523}} @article{Gramsbergen:1970, Author = {Gramsbergen, A and Schwartze, P and Prechtl, H F}, Date-Added = {2010-02-23 12:04:13 -0500}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Dev Psychobiol}, Journal-Full = {Developmental psychobiology}, Keywords = {21 Activity-development; Rats; Mouse; Behavior; Spontaneous activity}, Mesh = {Animals; Animals, Laboratory; Animals, Newborn; Behavior, Animal; Body Weight; Brain; Circadian Rhythm; Female; Housing, Animal; Locomotion; Male; Rats; Sleep; Startle Reaction; Wakefulness}, Number = {4}, Pages = {267-80}, pmid = {5527425}, Pst = {ppublish}, Title = {The postnatal development of behavioral states in the rat}, Volume = {3}, Year = {1970}, url = {papers/Gramsbergen_DevPsychobiol1970.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dev.420030407}} @article{Petersson:2003, Abstract = {During development, information about the three-dimensional shape and mechanical properties of the body is laid down in the synaptic connectivity of sensorimotor systems through unknown adaptive mechanisms. In spinal reflex systems, this enables the fast transformation of complex sensory information into adequate correction of movements. Here we use a computer simulation to show that an unsupervised correlation-based learning mechanism, using spontaneous muscle twitches, can account for the functional adaptation of the withdrawal reflex system. We also show that tactile feedback resulting from spontaneous muscle twitches during sleep does indeed modify sensorimotor transformation in young rats in a predictable manner. The results indicate that these twitches, corresponding to human fetal movements, are important in spinal self-organization.}, Author = {Petersson, Per and Waldenstr{\"o}m, Alexandra and F{\aa}hraeus, Christer and Schouenborg, Jens}, Date-Added = {2010-02-23 12:04:10 -0500}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Activity-development; Rats; Mouse; Behavior; Spontaneous activity}, Mesh = {Animals; Computer Simulation; Feedback; Female; Male; Models, Biological; Muscles; Rats; Rats, Wistar; Reflex; Sleep; Spine}, Month = {Jul}, Number = {6944}, Pages = {72-5}, pmid = {12840761}, Pst = {ppublish}, Title = {Spontaneous muscle twitches during sleep guide spinal self-organization}, Volume = {424}, Year = {2003}, url = {papers/Petersson_Nature2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01719}} @article{Stafford:2009, Abstract = {During development, retinal axons project coarsely within their visual targets before refining to form organized synaptic connections. Spontaneous retinal activity, in the form of acetylcholine-driven retinal waves, is proposed to be necessary for establishing these projection patterns. In particular, both axonal terminations of retinal ganglion cells (RGCs) and the size of receptive fields of target neurons are larger in mice that lack the beta2 subunit of the nicotinic acetylcholine receptor (beta2KO). Here, using a large-scale, high-density multielectrode array to record activity from hundreds of RGCs simultaneously, we present analysis of early postnatal retinal activity from both wild-type (WT) and beta2KO retinas. We find that beta2KO retinas have correlated patterns of activity, but many aspects of these patterns differ from those of WT retina. Quantitative analysis suggests that wave directionality, coupled with short-range correlated bursting patterns of RGCs, work together to refine retinofugal projections.}, Author = {Stafford, Ben K and Sher, Alexander and Litke, Alan M and Feldheim, David A}, Date-Added = {2009-11-17 12:42:08 -0500}, Date-Modified = {2013-05-21 20:36:03 +0000}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Cortical oscillations; 10 Development; 10 circuit formation; 10 Structural plasticity; retinal wave paper; currOpinRvw}, Mesh = {Action Potentials; Analysis of Variance; Animals; Animals, Newborn; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Neurological; Mutation; Probability; Receptors, Nicotinic; Retina; Retinal Ganglion Cells; Temperature; Time Factors; Visual Pathways}, Month = {Oct}, Number = {2}, Pages = {200-12}, pmid = {19874788}, Title = {Spatial-temporal patterns of retinal waves underlying activity-dependent refinement of retinofugal projections}, Volume = {64}, Year = {2009}, url = {papers/Stafford_Neuron2009.pdf}, Bdsk-File-2 = {papers/Stafford_Neuron2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.09.021}} @article{Wang:2009, Abstract = {Retinotopic mapping is a basic feature of visual system organization, but its role in processing visual information is unknown. Mutant mice lacking the beta2 subunit of nicotinic acetylcholine receptor have imprecise maps in both visual cortex (V1) and the superior colliculus (SC) due to the disruption of spontaneous retinal activity during development. Here, we use behavioral and physiological approaches to study their visual functions. We find that beta2-/- mice fail to track visual stimuli moving along the nasotemporal axis in a subcortical optomotor behavior, but track normally along the dorsoventral axis. In contrast, these mice display normal acuity along both axes in the visual water task, a behavioral test of cortical functions. Consistent with the behavioral results, we find that V1 neurons in beta2-/- mice have normal response properties, while SC neurons have disrupted receptive fields, including enlarged structure and decreased direction and orientation selectivity along the nasotemporal axis. The subcortical-specific deficits indicate that retinotopic map disruption has different impacts on the development of functional properties in V1 and the SC.}, Author = {Wang, Lupeng and Rangarajan, Krsna V and Lawhn-Heath, Courtney A and Sarnaik, Rashmi and Wang, Bor-Shuen and Liu, Xiaorong and Cang, Jianhua}, Date-Added = {2009-11-17 09:07:07 -0500}, Date-Modified = {2013-08-27 20:42:08 +0000}, Journal = {J Neurosci}, Journal-Full = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology;Spontaneous activity;retina;visual cortex;visual system;Superior Colliculus;optic tectum;function;in vivo; currOpinRvw}, Mesh = {Analysis of Variance; Animals; Brain Mapping; Disease Models, Animal; Evoked Potentials, Visual; Head Movements; Mice; Mice, Inbred C57BL; Mice, Knockout; Nystagmus, Optokinetic; Orientation; Perceptual Disorders; Photic Stimulation; Receptors, Nicotinic; Sensory Receptor Cells; Space Perception; Superior Colliculi; Visual Cortex; Visual Fields; Visual Pathways}, Month = {Oct}, Number = {41}, Pages = {12909-18}, pmid = {19828805}, Title = {Direction-specific disruption of subcortical visual behavior and receptive fields in mice lacking the beta2 subunit of nicotinic acetylcholine receptor}, Volume = {29}, Year = {2009}, url = {papers/Wang_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2128-09.2009}} @article{Hashimoto:2003, Abstract = {We studied how physiological properties of cerebellar climbing fiber (CF) to Purkinje cell (PC) synapses change during developmental transition from multiple to mono CF innervation onto each PC. From P3 to P6, differences in the strengths of multiple CFs became larger. Around P10, each PC was either monoinnervated by one strong CF (CF-mono) or multiply innervated by one strong CF (CF-multi-S) plus a few weaker CFs (CF-multi-W). We show that simultaneous release of multiple vesicles per site occurs normally from CF-multi-S, CF-mono, and mature CFs, but less frequently from CF-multi-W and neonatal CFs. We also present evidence suggesting that weaker CFs with lower probability of multivesicular release would be withdrawn preferentially. The results suggest that differentiation into strong and weak CFs with high and low probabilities of multivesicular release precedes developmental CF synapse elimination.}, Author = {Hashimoto, Kouichi and Kano, Masanobu}, Date-Added = {2009-08-18 11:39:05 -0400}, Date-Modified = {2009-08-18 11:39:44 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {10 Development; 10 circuit formation; 21 Neurophysiology}, Mesh = {Afferent Pathways; Aging; Animals; Animals, Newborn; Cell Differentiation; Cerebellar Cortex; Dendrites; Electric Stimulation; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Glutamic Acid; Mice; Mice, Inbred C57BL; Neuronal Plasticity; Presynaptic Terminals; Purkinje Cells; Receptors, AMPA; Receptors, N-Methyl-D-Aspartate; Synaptic Transmission; Synaptic Vesicles}, Month = {Jun}, Number = {5}, Pages = {785-96}, pmid = {12797962}, Title = {Functional differentiation of multiple climbing fiber inputs during synapse elimination in the developing cerebellum}, Volume = {38}, Year = {2003}, url = {papers/Hashimoto_Neuron2003.pdf}} @article{Hashimoto:2009, Abstract = {Functional neural circuits are formed by eliminating early-formed redundant synapses and strengthening necessary connections during development. In newborn mouse cerebellum, each Purkinje cell (PC) is innervated by multiple climbing fibers (CFs) with similar strengths. Subsequently, a single CF is selectively strengthened by postnatal day 7 (P7). We find that this competition among multiple CFs occurs on the soma before CFs form synapses along dendrites. Notably, in most PCs, the single CF that has been functionally strengthened (the "winner" CF) undergoes translocation to dendrites while keeping its synapses on the soma. Synapses of the weaker CFs (the "loser" CFs) remain around the soma and form "pericellular nests" with synapses of the winner CFs. Then most perisomatic synapses are eliminated nonselectively by P15. Thus, our results suggest that the selective translocation of the winner CF to dendrites in each PC determines the single CF that survives subsequent synapse elimination and persistently innervates the PC.}, Author = {Hashimoto, Kouichi and Ichikawa, Ryoichi and Kitamura, Kazuo and Watanabe, Masahiko and Kano, Masanobu}, Date-Added = {2009-08-18 11:32:55 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {10 Development; 10 circuit formation; 21 Neurophysiology}, Mesh = {Age Factors; Aminobutyric Acids; Analysis of Variance; Animals; Animals, Newborn; Biophysics; Biotin; Calcium-Binding Protein, Vitamin D-Dependent; Cerebellum; Dendrites; Dextrans; Electric Stimulation; Excitatory Postsynaptic Potentials; Green Fluorescent Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy, Confocal; Nerve Fibers; Nerve Net; Patch-Clamp Techniques; Purkinje Cells; Receptors, Serotonin; Synapses; Time Factors; Vesicular Glutamate Transport Protein 2}, Month = {Jul}, Number = {1}, Pages = {106-18}, pmid = {19607796}, Title = {Translocation of a "winner" climbing fiber to the Purkinje cell dendrite and subsequent elimination of "losers" from the soma in developing cerebellum}, Volume = {63}, Year = {2009}, url = {papers/Hashimoto_Neuron2009.pdf}, Bdsk-File-2 = {papers/Hashimoto_Neuron2009a.pdf}, Bdsk-File-3 = {papers/Hashimoto_Neuron2009b.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2009.06.008}} @article{Thong:1986, Abstract = {To study the development of the corticotectal pathway, the enzyme horseradish peroxidase (HRP) was injected electrophoretically into the superior colliculus (SC) of rats ranging in age from newborn to adult. In animals younger than postnatal day 3 (P3), collicular injections did not label any cells in the cortex while in animals injected at P3-P4, only a few cortical cells were retrogradely labeled. In contrast, injections made at P5 or later resulted in the labeling of a substantial proportion of lamina V cells in a number of cortical areas ipsilateral to the injected colliculus. Although at P5-P7 the bulk of labeled cells was located in the visual cortices (both striate and extrastriate), a substantial proportion of the labeled cells was located in the somatosensory, motor and association cortices. On the other hand, in animals injected at P12 (or later), the labeled cells were largely restricted to the visual cortices with relatively few corticotectal cells located in somatosensory area I. At all ages studied, labeled cortical cells were confined to lamina V and had clear-cut apical dendrites (pyramidal cells). The dendritic morphologies and somal sizes of the corticotectal cells indicate that in animals younger than P12 these cells are immature. These observations suggest that the axons of cortical cells do not reach the SC before P3 and that these early corticotectal projections (P3-P12) are established by immature cells. Furthermore, although the corticotectal projection exhibits, from its onset, a high degree of specificity in terms of the laminar distribution of its cells of origin, its areal distribution is 'exuberant'. The 'exuberant' projections originating from non-visual cortical areas disappear by P12-P14, that is at the time when young rats open their eyes for the first time.}, Author = {Thong, I G and Dreher, B}, Date-Added = {2009-07-30 11:49:09 -0400}, Date-Modified = {2009-07-30 11:49:53 -0400}, Journal = {Brain Res}, Journal-Full = {Brain research}, Keywords = {21 Neurophysiology; 21 Cortical oscillations; 21 Circuit structure-function; 21 Activity-development}, Mesh = {Aging; Animals; Brain Mapping; Cerebral Cortex; Horseradish Peroxidase; Microinjections; Neural Pathways; Rats; Rats, Inbred Strains; Stereotaxic Techniques; Superior Colliculi; Time Factors}, Month = {Mar}, Number = {2}, Pages = {227-38}, pmid = {3513902}, Title = {The development of the corticotectal pathway in the albino rat}, Volume = {390}, Year = {1986}} @article{Thong:1987, Abstract = {In rats ranging in age from the second postnatal day (23rd postconceptional day-23 PCD) to adulthood, we have studied the distribution of corticotectal terminals labelled anterogradely by unilateral injections of horseradish peroxidase (conjugated with wheat germ agglutinin) into the visual or motor cortices. No projection to the contralateral superior colliculus (SC) was observed. The earliest age at which the labelled axons and/or terminals from the visual cortex were observed in the ipsilateral SC was 25 PCD. At this stage the projection only involves the optic layer. From 28 to 34 PCD, the projection involves the optic layer, the intermediate layers and the deep part of superficial gray layer. Between 34 and 40 PCD the projection becomes restricted to the superficial laminae (i.e. adultlike). On the 23 PCD (the earliest age examined) we observed a projection from the motor cortex to the intermediate laminae and to a lesser extent the optic layer of the ipsilateral SC. By 34 PCD only the adult-like projection extending from the brachium to the periaqueductal gray (PAG) is apparent. The disappearance of the transient projections to the intermediate collicular laminae may be the result of withdrawal of 'misprojecting' axonal collaterals.}, Author = {Thong, I G and Dreher, B}, Date-Added = {2009-07-30 11:46:27 -0400}, Date-Modified = {2009-07-30 11:48:06 -0400}, Journal = {Neurosci Lett}, Journal-Full = {Neuroscience letters}, Keywords = {21 Neurophysiology; 21 Cortical oscillations; 21 Circuit structure-function; 21 Activity-development}, Mesh = {Animals; Horseradish Peroxidase; Motor Cortex; Neuronal Plasticity; Rats; Rats, Inbred Strains; Superior Colliculi; Visual Cortex; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate; Wheat Germ Agglutinins}, Month = {Oct}, Number = {3}, Pages = {275-82}, pmid = {2446211}, Title = {The development of the corticotectal pathway in the albino rat: transient projections from the visual and motor cortices}, Volume = {80}, Year = {1987}, url = {papers/Thong_NeurosciLett1987.pdf}} @article{Wallace:2000, Abstract = {Many neurons in the superior colliculus (SC) are able to integrate combinations of visual, auditory, and somatosensory stimuli, thereby markedly affecting the vigor of their responses to external stimuli. However, this capacity for multisensory integration is not inborn. Rather, it appears comparatively late in postnatal development and is not expressed until the SC passes through several distinct developmental stages. As shown here, the final stage in this sequence is one in which a region of association cortex establishes functional control over the SC, thus enabling the multisensory integrative capabilities of its target SC neurons. The first example of this corticotectal input was seen at postnatal day 28. For any individual SC neuron, the onset of corticotectal influences appeared to be abrupt. Because this event occurred at very different times for different SC neurons, a period of 3-4 postnatal months was required before the adult-like condition was achieved. The protracted postnatal period required for the maturation of these corticotectal influences corresponded closely with estimates of the peak period of cortical plasticity, raising the possibility that the genesis of these corticotectal influences, and hence the onset of SC multisensory integration, occurs only after the cortex is capable of exerting experience-dependent control over SC neurons.}, Author = {Wallace, M T and Stein, B E}, Date-Added = {2009-07-30 11:42:48 -0400}, Date-Modified = {2009-07-30 11:45:30 -0400}, Journal = {J Neurophysiol}, Journal-Full = {Journal of neurophysiology}, Keywords = {21 Neurophysiology; 21 Cortical oscillations; 21 Circuit structure-function; 21 Activity-development}, Mesh = {Algorithms; Animals; Animals, Newborn; Cerebral Cortex; Hearing; Rats; Sensation; Superior Colliculi; Vision, Ocular}, Month = {Jun}, Number = {6}, Pages = {3578-82}, pmid = {10848574}, Title = {Onset of cross-modal synthesis in the neonatal superior colliculus is gated by the development of cortical influences}, Volume = {83}, Year = {2000}, url = {papers/Wallace_JNeurophysiol2000.pdf}} @conference{Ackman:2000, Author = {Ackman, James B. and LoTurco, Joseph J.}, Date-Added = {2009-07-28 17:04:58 -0400}, Date-Modified = {2009-07-28 17:09:19 -0400}, Journal = {Soc Neurosci Abstr}, Title = {Barrel formation and deformation in the neocortex of the flathead mutant}, Year = {2000}} @article{Feller:2009, Abstract = {Prior to eye-opening and the development of visual responses, the retina exhibits highly correlated spontaneous firing pattens termed retinal waves. Disruption of the normal spontaneous firing pattern either genetically or pharmacologically prevents the eye-specific refinement of retinogeniculate afferents. Here I provide the evidence that retinal waves play an instructive role in this process. In addition, I argue that a full understanding requires an identification of the features of retinal activity that drive the refinement as well as an understanding of mechanisms that transform these signals into axonal rearrangements.}, Author = {Feller, Marla B}, Date-Added = {2009-07-14 16:00:48 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Neural Dev}, Journal-Full = {Neural development}, Keywords = {21 Activity-development; 21 Cortical oscillations;21 Neurophysiology; retinal wave paper}, Pages = {24}, pmid = {19580682}, Title = {Retinal waves are likely to instruct the formation of eye-specific retinogeniculate projections}, Volume = {4}, Year = {2009}, url = {papers/Feller_NeuralDev2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1749-8104-4-24}} @article{Chalupa:2009, Abstract = {In all mammalian species the projections of the two eyes to the dorsal lateral geniculate nucleus are initially overlapping before gradually forming the eye-specific domains evident at maturity. It is widely thought that retinal waves of neuronal activity play an instructional role in this developmental process. Here, I discuss the myriad reasons why retinal waves are unlikely to have such a role, and suggest that eye-specific molecular cues in combination with neuronal activity are most probably involved in the formation of eye-specific retinogeniculate projections.}, Author = {Chalupa, Leo M}, Date-Added = {2009-07-14 15:57:53 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Neural Dev}, Journal-Full = {Neural development}, Keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology; retinal wave paper}, Pages = {25}, pmid = {19580684}, Title = {Retinal waves are unlikely to instruct the formation of eye-specific retinogeniculate projections}, Volume = {4}, Year = {2009}, url = {papers/Chalupa_NeuralDev2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1749-8104-4-25}} @article{Vries:1982, Author = {de Vries, J I and Visser, G H and Prechtl, H F}, Date-Added = {2009-07-14 13:57:01 -0400}, Date-Modified = {2009-07-14 13:57:01 -0400}, Journal = {Early Hum Dev}, Journal-Full = {Early human development}, Mesh = {Adult; Female; Fetus; Gestational Age; Humans; Movement; Posture; Pregnancy; Ultrasonography}, Month = {Dec}, Number = {4}, Pages = {301-22}, pmid = {7169027}, Title = {The emergence of fetal behaviour. I. Qualitative aspects}, Volume = {7}, Year = {1982}, url = {papers/Vries_EarlyHumDev1982.pdf}} @article{Clancy:2001, Abstract = {Conservation of the order in which events occur in developing mammalian brains permits use of regression theory to model the timing of neural development. Following a small adjustment to account for a systematic variability in primate cortical and limbic systems, the model is used to generate a 95-event/nine-species matrix that predicts aspects of neurogenesis and axonal outgrowth in the brains of developing mice, hamsters, rats, spiny mice, rabbits, ferrets, cats, monkeys, and humans. Although data are compiled from species in which the timing of birth and the rate of maturation vary widely, the model proves statistically accurate, with practical implications for improving estimation of milestones of neural development, particularly for humans. Using the three-factor model (species, neural events, and primate adjustments), we produce predictions for the timing of 493 neural occurrences in developing mammalian brains that either have not yet been, or cannot be, empirically derived. We also relate the timing of neural events across the nine species in the form of a reference table calibrated to the development of laboratory rats. This 'translation' table will assist in attempts to equate the neurodevelopmental literature across species with either large or small differences in gestation and maturation, and also permit studies done in a variety of mammals to be applied to better understand human development. The comparative data indicate that humans, although conventionally considered an altricial species, are neurally advanced at birth relative to the other species studied.}, Author = {Clancy, B and Darlington, R B and Finlay, B L}, Date-Added = {2009-07-14 13:06:45 -0400}, Date-Modified = {2009-07-14 13:07:49 -0400}, Journal = {Neuroscience}, Journal-Full = {Neuroscience}, Keywords = {10 Development; 10 circuit formation; 19 Neocortical evolution}, Mesh = {Aging; Animals; Body Patterning; Brain; Cell Differentiation; Cell Division; Humans; Mammals; Models, Neurological; Phylogeny; Reproducibility of Results; Statistical Distributions}, Number = {1}, Pages = {7-17}, pmid = {11483296}, Title = {Translating developmental time across mammalian species}, Volume = {105}, Year = {2001}, url = {papers/Clancy_Neuroscience2001.pdf}} @article{Juttner:2001, Abstract = {During postnatal development, the retinocollicular pathway undergoes activity-dependent refinement, resulting in the precise retinotopic map seen in adults. Previous studies established that retinal efferents reach the mouse superior colliculus (SC) by embryonic day 16. Morphologically, synapses were found in the rat SC before birth. As part of an extended project aimed at understanding the development of synaptic transmission in the visual layers of the SC, we report here the presence of functionally active synapses immediately after birth. Circuit activity in mouse SC neurons was detected in horizontal slices of the visual layers using cell-attached voltage clamp. The spontaneous discharge of action potentials was abolished by glutamatergic blockers and facilitated by bicuculline, showing that circuit activity is based on synaptic transmission and that the action of gamma-aminobutyric acid is inhibitory. Using whole-cell voltage clamp, spontaneous glutamatergic postsynaptic currents as well as miniature GABAergic postsynaptic currents were recorded on postnatal day 1. Excitatory and inhibitory postsynaptic currents could also be evoked by electrical stimulation. Glutamatergic postsynaptic currents comprised both (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and N-methyl-D-aspartate receptor-mediated components. The early function of glutamatergic and GABAergic synaptic transmission in the visual layers of SC suggests that SC neurons are able to process information originating from retinal axons immediately after birth.}, Author = {J{\"u}ttner, R and Henneberger, C and Grantyn, R and Rothe, T}, Date-Added = {2009-07-13 15:22:41 -0400}, Date-Modified = {2009-07-13 15:23:06 -0400}, Journal = {Int J Dev Neurosci}, Journal-Full = {International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Mesh = {2-Amino-5-phosphonovalerate; Animals; Animals, Newborn; Bicuculline; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; GABA Antagonists; Glutamic Acid; Mice; Mice, Inbred C57BL; Nicotinic Antagonists; Organ Culture Techniques; Quinoxalines; Rats; Rats, Wistar; Species Specificity; Superior Colliculi; Synaptic Transmission; Tubocurarine; gamma-Aminobutyric Acid}, Month = {Jun}, Number = {3}, Pages = {255-61}, pmid = {11337194}, Title = {Early onset of glutamatergic and GABAergic synaptic activity in the visual layers of the rodent superior colliculus}, Volume = {19}, Year = {2001}} @article{Mark:1993, Abstract = {The retinocollicular projection in the marsupial mammal the wallaby Macropus eugenii, has been investigated anatomically to determine the order in the developing projection and electrophysiologically to determine the time of onset of synaptic transmission by recording evoked potentials in the colliculus in response to stimulation of the optic nerve. There are two clear stages: a protracted period when retinal axons grow into the colliculus in coarse retinotopic order with no recordable electrical activity followed by the formation of terminal zones in retinotopically correct positions, the loss of more widely distributed axons and the onset of evoked potentials. The two stages are not seen in non-mammalian vertebrates where the projection is functional from the beginning.}, Author = {Mark, R F and Freeman, T C and Ding, Y and Marotte, L R}, Date-Added = {2009-07-13 15:18:36 -0400}, Date-Modified = {2009-07-13 15:18:58 -0400}, Journal = {Neuroreport}, Journal-Full = {Neuroreport}, Keywords = {21 Neurophysiology; 21 Activity-development}, Mesh = {Animals; Axons; Brain Mapping; Evoked Potentials, Visual; Macropodidae; Optic Nerve; Retina; Species Specificity; Superior Colliculi; Visual Pathways}, Month = {Nov}, Number = {2}, Pages = {117-20}, pmid = {8110999}, Title = {Two stages in the development of a mammalian retinocollicular projection}, Volume = {5}, Year = {1993}} @article{Weliky:1999, Abstract = {The properties of spontaneous activity in the developing visual pathway beyond the retina are unknown. Multielectrode recordings in the lateral geniculate nucleus (LGN) of awake behaving ferrets, before eye opening, revealed patterns of spontaneous activity that reflect a reshaping of retinal drive within higher visual stages. Significant binocular correlations were present only when cortico-thalamic feedback was intact. In the absence of retinal drive, cortico-thalamic feedback was required to sustain correlated LGN bursting. Activity originating from the contralateral eye drove thalamic activity far more strongly than that originating from the ipsilateral eye. Thus, in vivo patterns of LGN spontaneous activity emerge from interactions between retina, thalamus, and cortex.}, Author = {Weliky, M and Katz, L C}, Date-Added = {2009-07-10 18:13:59 -0400}, Date-Modified = {2013-05-21 20:36:03 +0000}, Journal = {Science}, Journal-Full = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Cortical oscillations; retinal wave paper; currOpinRvw}, Mesh = {Action Potentials; Animals; Denervation; Electrodes; Feedback; Ferrets; Geniculate Bodies; Models, Neurological; Neurons; Optic Nerve; Retina; Retinal Ganglion Cells; Thalamus; Visual Cortex; Visual Pathways}, Month = {Jul}, Number = {5427}, Pages = {599-604}, pmid = {10417392}, Title = {Correlational structure of spontaneous neuronal activity in the developing lateral geniculate nucleus in vivo}, Volume = {285}, Year = {1999}, url = {papers/Weliky_Science1999.pdf}, Bdsk-Url-1 = {http://www.sciencemag.org/cgi/content/full/285/5427/541}} @article{Wong:1995, Abstract = {In the adult mammalian retina, the principal direction of information flow is along a vertical pathway from photoreceptors to retinal interneurons to ganglion cells, the output neurons of the retina. We report here, however, that initially in development, at a time when the photoreceptors are not yet even present, there are already functionally defined networks within the retina. These networks are spontaneously active rather than visually driven, and they involve horizontal rather than vertical pathways. By means of optical recording using the calcium-sensitive dye Fura-2, we have found that sets of retinal ganglion cells and amacrine cells, a type of retinal interneuron, undergo synchronized oscillations in intracellular calcium concentration. These oscillations are highly correlated among subgroups of neighbouring cells, and spread in a wave-like fashion tangentially across the retina. Thus, in development of retinal circuitry, the initial patterning of neuronal function occurs in the horizontal domain before the adult pattern of vertical information transfer emerges.}, Author = {Wong, R O and Chernjavsky, A and Smith, S J and Shatz, C J}, Date-Added = {2009-07-10 16:18:53 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Journal = {Nature}, Journal-Full = {Nature}, Keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology; retinal wave paper}, Mesh = {Animals; Animals, Newborn; Calcium; Ferrets; Interneurons; Nerve Net; Retina; Retinal Ganglion Cells}, Month = {Apr}, Number = {6524}, Pages = {716-8}, pmid = {7715725}, Title = {Early functional neural networks in the developing retina}, Volume = {374}, Year = {1995}, url = {papers/Wong_Nature1995.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/374716a0}} @article{Wong:1993, Abstract = {The refinement of early connections in the visual pathway requires electrical activity in the retina before the onset of vision. Using a multielectrode array, we have shown that the spontaneous activity of cells in the neonatal ferret retina is correlated by patterns of periodically generated traveling waves. Here, we examine developmental changes in the characteristics of the waves and show that retinal ganglion cells participate in these patterns of activity, which are seen during the same period as synaptic modification in the lateral geniculate nucleus; that the waves subside gradually as the connectivity in the lateral geniculate nucleus stabilizes; and that their spatial structure allows for refinement of the retinotopic map, as well as for eye-specific segregation in the lateral geniculate nucleus.}, Author = {Wong, R O and Meister, M and Shatz, C J}, Date-Added = {2009-07-10 16:12:11 -0400}, Date-Modified = {2010-10-01 05:48:09 -0400}, Journal = {Neuron}, Journal-Full = {Neuron}, Keywords = {21 Neurophysiology; 21 Cortical oscillations; 21 Activity-development; retinal wave paper}, Mesh = {Aging; Animals; Animals, Newborn; Electrophysiology; Ferrets; Retina; Retinal Ganglion Cells; Time Factors}, Month = {Nov}, Number = {5}, Pages = {923-38}, pmid = {8240814}, Title = {Transient period of correlated bursting activity during development of the mammalian retina}, Volume = {11}, Year = {1993}, url = {papers/Wong_Neuron1993.pdf}} @article{Jiang:2003, Abstract = {The manner in which the nervous system allocates limited motor resources when confronted with conflicting behavioural demands is a crucial issue in understanding how sensory information is transformed into adaptive motor responses. Understanding this selection process is of particular concern in current models of functions of the basal ganglia. Here we report that the basal ganglia use simultaneous enhancing and suppressing processes synergistically to modulate sensory activity in the superior colliculi, which are bilaterally paired midbrain structures involved in the control of visual orientation behaviours. These complementary processes presumably ensure accurate gaze shifts mediated by the superior colliculi despite the presence of potential distractors.}, Address = {Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.}, Author = {Jiang, Huai and Stein, Barry E and McHaffie, John G}, Crdt = {2003/06/27 05:00}, Da = {20030626}, Date = {2003 Jun 26}, Date-Added = {2009-05-22 10:40:28 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20030801}, Edat = {2003/06/27 05:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Basal Ganglia/*physiology; Cats; Eye Movements/*physiology; Fixation, Ocular/physiology; Functional Laterality; Male; Neural Inhibition; Neurons/physiology; Parvalbumins/physiology; Photic Stimulation; Superior Colliculi/*physiology; gamma-Aminobutyric Acid/physiology}, Mhda = {2003/08/02 05:00}, Month = {Jun}, Number = {6943}, Own = {NLM}, Pages = {982--986}, Phst = {2003/02/19 {$[$}received{$]$}; 2003/04/23 {$[$}accepted{$]$}}, Pii = {nature01698}, Pl = {England}, pmid = {12827201}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Parvalbumins); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Opposing basal ganglia processes shape midbrain visuomotor activity bilaterally}, Volume = {423}, Year = {2003}, url = {papers/Jiang_Nature2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01698}} @article{Mongeau:2003, Abstract = {Environment and experience influence defensive behaviors, but the neural circuits mediating such effects are not well understood. We describe a new experimental model in which either flight or freezing reactions can be elicited from mice by innately aversive ultrasound. Flight and freezing are negatively correlated, suggesting a competition between fear motor systems. An unfamiliar environment or a previous aversive event, moreover, can alter the balance between these behaviors. To identify potential circuits controlling this competition, global activity patterns in the whole brain were surveyed in an unbiased manner by c-fos in situ hybridization, using novel experimental and analytical methods. Mice predominantly displaying freezing behavior had preferential neural activity in the lateral septum ventral and several medial and periventricular hypothalamic nuclei, whereas mice predominantly displaying flight had more activity in cortical, amygdalar, and striatal motor areas, the dorsolateral posterior zone of the hypothalamus, and the vertical limb of the diagonal band. These complementary patterns of c-fos induction, taken together with known connections between these structures, suggest ways in which the brain may mediate the balance between these opponent defensive behaviors.}, Address = {Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.}, Author = {Mongeau, Raymond and Miller, Gabriel A and Chiang, Elizabeth and Anderson, David J}, Crdt = {2003/05/09 05:00}, Da = {20030508}, Date = {2003 May 1}, Date-Added = {2009-04-08 18:17:57 -0400}, Date-Modified = {2009-04-08 18:19:10 -0400}, Dcom = {20030619}, Edat = {2003/05/09 05:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Acoustic Stimulation/instrumentation/methods; Animals; Anxiety; Behavior, Animal/*physiology; Brain/cytology/metabolism/*physiology; Brain Mapping; Electroshock; Escape Reaction/physiology; Fear/*physiology; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Neurons/*metabolism; Proto-Oncogene Proteins c-fos/genetics/metabolism; RNA, Messenger/metabolism; Ultrasonics}, Mhda = {2003/06/20 05:00}, Month = {May}, Number = {9}, Own = {NLM}, Pages = {3855--3868}, Pii = {23/9/3855}, Pl = {United States}, pmid = {12736356}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Proto-Oncogene Proteins c-fos); 0 (RNA, Messenger)}, Sb = {IM}, Status = {MEDLINE}, Title = {Neural correlates of competing fear behaviors evoked by an innately aversive stimulus}, Volume = {23}, Year = {2003}, url = {papers/Mongeau_JNeurosci2003.pdf}} @article{Haider:2008, Abstract = {The neuropsychological concepts found in Donald Hebb's The Organization of Behavior have greatly influenced many aspects of neuroscience research over the last half century. Hebb's ideas arose from a rich tradition of research. An underappreciated contribution came from pioneering studies at Yale University. Here, we wish to reconsider these developments, placing particular emphasis on the roles of the neurophysiologists John Fulton, J.J. Dusser de Barenne, and Warren McCulloch and the psychologists Donald Marquis and Ernest Hilgard. These neuroscientists all contributed significantly to the intellectual climate that gave rise to Hebb's remarkable synthesis.}, Address = {Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. bilal.haider@yale.edu}, Author = {Haider, Bilal}, Crdt = {2008/07/08 09:00}, Da = {20080708}, Date = {2008 Mar}, Date-Added = {2009-04-08 18:14:47 -0400}, Date-Modified = {2009-04-08 18:17:47 -0400}, Dcom = {20080811}, Edat = {2008/07/08 09:00}, Issn = {1551-4056 (Electronic)}, Jid = {0417414}, Journal = {Yale J Biol Med}, Jt = {The Yale journal of biology and medicine}, Keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20081120}, Mh = {*Behavior; Humans}, Mhda = {2008/08/12 09:00}, Month = {Mar}, Number = {1}, Oid = {NLM: PMC2442722}, Own = {NLM}, Pages = {11--18}, Pl = {United States}, Pmc = {PMC2442722}, pmid = {18604307}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Source = {Yale J Biol Med. 2008 Mar;81(1):11-8.}, Status = {MEDLINE}, Title = {Contributions of Yale neuroscience to Donald O. Hebb's organization of behavior}, Volume = {81}, Year = {2008}, url = {papers/Haider_YaleJBiolMed2008.pdf}} @article{Shu:2003, Abstract = {The vast majority of synaptic connections onto neurons in the cerebral cortex arise from other cortical neurons, both excitatory and inhibitory, forming local and distant 'recurrent' networks. Although this is a basic theme of cortical organization, its study has been limited largely to theoretical investigations, which predict that local recurrent networks show a proportionality or balance between recurrent excitation and inhibition, allowing the generation of stable periods of activity. This recurrent activity might underlie such diverse operations as short-term memory, the modulation of neuronal excitability with attention, and the generation of spontaneous activity during sleep. Here we show that local cortical circuits do indeed operate through a proportional balance of excitation and inhibition generated through local recurrent connections, and that the operation of such circuits can generate self-sustaining activity that can be turned on and off by synaptic inputs. These results confirm the long-hypothesized role of recurrent activity as a basic operation of the cerebral cortex.}, Address = {Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.}, Author = {Shu, Yousheng and Hasenstaub, Andrea and McCormick, David A}, Crdt = {2003/05/16 05:00}, Da = {20030515}, Date = {2003 May 15}, Date-Added = {2009-04-08 18:14:47 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20030610}, Edat = {2003/05/16 05:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials; Animals; Cerebral Cortex/cytology/*physiology; Electric Stimulation; Excitatory Postsynaptic Potentials/physiology; Ferrets/*physiology; Interneurons/physiology; Nerve Net/cytology/physiology; Neurons/*physiology; Pyramidal Cells/physiology; Synapses/physiology}, Mhda = {2003/06/11 05:00}, Month = {May}, Number = {6937}, Own = {NLM}, Pages = {288--293}, Phst = {2002/12/12 {$[$}received{$]$}; 2003/03/28 {$[$}accepted{$]$}}, Pii = {nature01616}, Pl = {England}, pmid = {12748642}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Nature. 2003 May 15;423(6937):288-93.}, Status = {MEDLINE}, Title = {Turning on and off recurrent balanced cortical activity}, Volume = {423}, Year = {2003}, url = {papers/Shu_Nature2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01616}} @Article{Seung:2000, author = {Seung, H S}, title = {Half a century of Hebb}, journal = {Nat Neurosci}, year = {2000}, volume = {3 Suppl}, pages = {1166}, month = {Nov}, issn = {1097-6256 (Print)}, address = {Howard Hughes Medical Institute and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA. seung@mit.edu}, doi = {10.1038/81430}, crdt = {2000/12/29 11:00}, da = {20001220}, date = {2000 Nov}, date-added = {2009-04-08 18:14:47 -0400}, date-modified = {2011-09-12 11:19:15 -0400}, dcom = {20010104}, edat = {2000/12/29 11:00}, file = {papers/Seung_NatNeurosci2000.pdf}, jid = {9809671}, jt = {Nature neuroscience}, keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology}, language = {eng}, lr = {20041117}, mh = {Animals; History, 20th Century; Humans; Long-Term Potentiation/*physiology; Memory/physiology; Nerve Net/cytology/physiology; Neuronal Plasticity/physiology; Synapses/*physiology; Synaptic Transmission/*physiology}, mhda = {2001/02/28 10:01}, own = {NLM}, pl = {United States}, pmid = {11127829}, pst = {ppublish}, pt = {Biography; Historical Article; Journal Article}, sb = {IM}, source = {Nat Neurosci. 2000 Nov;3 Suppl:1166.}, status = {MEDLINE}, } @article{Steriade:1993c, Abstract = {As most afferent axons to the thalamus originate in the cerebral cortex, we assumed that the slow (< 1 Hz) cortical oscillation described in the two companion articles is reflected in reticular (RE) thalamic and thalamocortical cells. We hypothesized that the cortically generated slow rhythm would appear in the thalamus in conjunction with delta and spindle oscillations arising from intrinsic and network properties of thalamic neurons. Intracellular recordings have been obtained in anesthetized cats from RE (n = 51) and cortically projecting (n = 240) thalamic neurons. RE cells were physiologically identified by cortically evoked high-frequency spike bursts and depolarizing spindle oscillations. Thalamocortical cells were recognized by backfiring from appropriate neocortical areas, spindle-related cyclic IPSPs, and hyperpolarization-activated delta oscillation consisting of rhythmic low-threshold spikes (LTSs) alternating with afterhyperpolarizing potentials (AHPs). The slow rhythm (0.3-0.5 Hz) was recorded in 65% of RE neurons. In approximately 90% of oscillating cells, the rhythm consisted of prolonged depolarizations giving rise to trains of single action potentials. DC hyperpolarization increased the synaptic noise and, in a few cells, suppressed the long-lasting depolarizing phase of the slow rhythm, without blocking the fast EPSPs. In approximately 10% of oscillating neurons, the hyperpolarizing phase of the oscillation was much more pronounced, thus suggesting that the slow rhythm was produced by inhibitory sculpturing of the background firing. The slow oscillation was associated with faster rhythms (4-8 Hz) in the same RE neuron. The slow rhythm of RE neurons was closely related to EEG wave complexes recurring with the same frequency, and its strong dependency upon a synchronized state of cortical EEG was observed during shifts in EEG patterns at different levels of anesthesia. In 44% of thalamocortical cells the slow rhythm of depolarizing sequences was apparent and it could coexist with delta or spindle oscillations in the same neuron. The occurrence of the slowly recurring depolarizing envelopes was delayed by the hyperpolarizing spindle sequences or by the LTS-AHP sequences of delta oscillation. The hyperpolarization-activated delta potentials that tended to dampen after a few cycles were grouped in sequences recurring with the slow rhythm. We finally propose a unified scenario of the genesis of the three major sleep rhythms: slow, delta, and spindle oscillations.}, Address = {Laboratoire de Neurophysiologie, Faculte de Medecine, Universite Laval, Quebec, Canada.}, Author = {Steriade, M and Contreras, D and Curro Dossi, R and Nunez, A}, Crdt = {1993/08/01 00:00}, Da = {19930902}, Date = {1993 Aug}, Date-Added = {2009-04-08 18:14:47 -0400}, Date-Modified = {2014-09-11 18:37:49 +0000}, Dcom = {19930902}, Edat = {1993/08/01}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials; Animals; Cats; Cerebral Cortex/cytology/*physiology; Electroencephalography; Electrophysiology; Evoked Potentials; Neurons/*physiology; Periodicity; Sleep/*physiology; Synapses/physiology; Thalamus/cytology/*physiology}, Mhda = {1993/08/01 00:01}, Month = {Aug}, Number = {8}, Own = {NLM}, Pages = {3284--3299}, Pl = {UNITED STATES}, pmid = {8340808}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {J Neurosci. 1993 Aug;13(8):3284-99.}, Status = {MEDLINE}, Title = {The slow (< 1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks}, Volume = {13}, Year = {1993}, url = {papers/Steriade_JNeurosci1993.pdf}} @article{Steriade:1993b, Abstract = {The newly described slow cortical rhythm (approximately 0.3 Hz), whose depolarizing-hyperpolarizing components are analyzed in the preceding article, is now investigated from the standpoint of its relations with delta (1-4 Hz) and spindle (7-14 Hz) rhythmicity. Regular-spiking and intrinsically bursting cortical neurons were mostly recorded from association suprasylvian areas 5 and 7; fewer neurons were also recorded from pericruciate motor and posterolateral visual areas. Although most cells were investigated under various anesthetics, a similar slow cortical rhythm was found in animals with brainstem transection at the low- or high-collicular levels. These cerveau isole (isolated forebrain) preparations display the major sleep rhythms of the EEG in the absence of general anesthetics. In 38% of recorded cortical neurons (n = 105), the slow rhythm was combined with delta oscillation. Both cellular rhythms were phase locked to the slow and delta oscillations in the surface- and depth-recorded EEG. In a group of this cell sample (n = 47), delta activity occurred as stereotyped, clock-like action potentials during the interdepolarization lulls of the slow rhythm. In another neuronal subsample (n = 58), delta events were grouped in sequences superimposed upon the depolarizing envelope of the slow rhythm, with such sequences recurring rhythmically at approximately 0.3-0.4 Hz. The associations between the two cellular and EEG rhythms (1-4 Hz and 0.3-0.4 Hz) were quantified by means of autocorrelograms, cross-correlograms, and spike-triggered averages. In 26% of recorded neurons (n = 72), the slow rhythm was combined with spindle oscillations. Regular-spiking cortical neurons fully reflected the whole frequency range of thalamically generated spindles (7-14 Hz). However, during similar patterns of EEG spindling, intrinsically bursting cells fired grouped action potentials (with intraburst frequencies of 100-200 Hz) at only 2-4 Hz. The dependence of the slow cortical oscillation upon the thalamus was studied by lesions and stimulation. The slow rhythm survived extensive ipsilateral thalamic destruction by means of electrolytic lesions or kainate-induced loss of perikarya in thalamic nuclei that were input sources to the recorded cortical neurons. To further prevent the possibility of a thalamic role in the genesis of the slow rhythm, through the contralateral thalamocortical systems and callosal projections, we also transected the corpus callosum in thalamically lesioned animals, and still recorded the slow rhythm in cortical neurons. These data indicate that the thalamus is not essentially implicated in the genesis of the slow rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)}, Address = {Laboratoire de Neurophysiologie, Faculte de Medecine, Universite Laval, Quebec, Canada.}, Author = {Steriade, M and Nunez, A and Amzica, F}, Crdt = {1993/08/01 00:00}, Da = {19930902}, Date = {1993 Aug}, Date-Added = {2009-04-08 18:14:47 -0400}, Date-Modified = {2014-09-11 18:38:10 +0000}, Dcom = {19930902}, Edat = {1993/08/01}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials; Animals; Cats; Cerebral Cortex/drug effects/*physiology; Corpus Callosum/physiology; Electric Stimulation; *Electroencephalography; Electrolysis; Electrophysiology; Humans; Kainic Acid/pharmacology; Ketamine/pharmacology; Neurons/physiology; Periodicity; Sleep/*physiology; Thalamus/drug effects/physiology; Urethane/pharmacology}, Mhda = {1993/08/01 00:01}, Month = {Aug}, Number = {8}, Own = {NLM}, Pages = {3266--3283}, Pl = {UNITED STATES}, pmid = {8340807}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {487-79-6 (Kainic Acid); 51-79-6 (Urethane); 6740-88-1 (Ketamine)}, Sb = {IM}, Source = {J Neurosci. 1993 Aug;13(8):3266-83.}, Status = {MEDLINE}, Title = {Intracellular analysis of relations between the slow (< 1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram}, Volume = {13}, Year = {1993}, url = {papers/Steriade_JNeurosci1993a.pdf}} @article{Steriade:1993a, Abstract = {We describe a novel slow oscillation in intracellular recordings from cortical association areas 5 and 7, motor areas 4 and 6, and visual areas 17 and 18 of cats under various anesthetics. The recorded neurons (n = 254) were antidromically and orthodromically identified as corticothalamic or callosal elements receiving projections from appropriate thalamic nuclei as well as from homotopic foci in the contralateral cortex. Two major types of cells were recorded: regular-spiking (mainly slow-adapting, but also fast-adapting) neurons and intrinsically bursting cells. A group of slowly oscillating neurons (n = 21) were intracellularly stained and found to be pyramidal-shaped cells in layers III-VI, with luxuriant basal dendritic arbors. The slow rhythm appeared in 88% of recorded neurons. It consisted of slow depolarizing envelopes (lasting for 0.8-1.5 sec) with superimposed full action potentials or presumed dendritic spikes, followed by long-lasting hyperpolarizations. Such sequences recurred rhythmically at less than 1 Hz, with a prevailing oscillation between 0.3 and 0.4 Hz in 67% of urethane-anesthetized animals. While in most neurons (approximately 70%) the repetitive spikes superimposed on the slow depolarization were completely blocked by slight DC hyperpolarization, 30% of cells were found to display relatively small (3-12 mV), rapid, all-or-none potentials after obliteration of full action potentials. These fast spikes were suppressed in an all-or-none fashion at Vm more negative than -90 mV. The depolarizing envelope of the slow rhythm was reduced or suppressed at a Vm of -90 to -100 mV and its duration was greatly reduced by administration of the NMDA blocker ketamine. In keeping with this action, most (56%) neurons recorded in animals under ketamine and nitrous oxide or ketamine and xylazine anesthesia displayed the slow oscillation at higher frequencies (0.6-1 Hz) than under urethane anesthesia (0.3-0.4 Hz). In 18% of the oscillating cells, the slow rhythm mainly consisted of repetitive (15-30 Hz), relatively short-lasting (15-25 msec) IPSPs that could be revealed by bringing the Vm at more positive values than -70 mV. The long-lasting (approximately 1 sec) hyperpolarizing phase of the slow oscillation was best observed at the resting Vm and was reduced at about -100 mV. Simultaneous recording of another cell across the membrane demonstrated synchronous inhibitory periods in both neurons. Intracellular diffusion of Cl- or Cs+ reduced the amplitude and/or duration of cyclic long-lasting hyperpolaryzations.(ABSTRACT TRUNCATED AT 400 WORDS)}, Address = {Laboratoire de Neurophysiologie, Faculte de Medecine, Universite Laval, Quebec, Canada.}, Author = {Steriade, M and Nunez, A and Amzica, F}, Crdt = {1993/08/01 00:00}, Da = {19930902}, Date = {1993 Aug}, Date-Added = {2009-04-08 18:14:47 -0400}, Date-Modified = {2014-09-11 18:38:16 +0000}, Dcom = {19930902}, Edat = {1993/08/01}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials/drug effects; Animals; Cats; Cerebral Cortex/cytology/*physiology; Dendrites/physiology; Electrophysiology; Humans; Ketamine/pharmacology; Lidocaine/analogs \& derivatives/pharmacology; Motor Cortex/physiology; Neural Pathways/physiology; Neurons/*physiology; Nitrous Oxide/pharmacology; Periodicity; Sleep/physiology; Thalamus/cytology/physiology; Visual Cortex/physiology; Xylazine/pharmacology}, Mhda = {1993/08/01 00:01}, Month = {Aug}, Number = {8}, Own = {NLM}, Pages = {3252--3265}, Pl = {UNITED STATES}, pmid = {8340806}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {10024-97-2 (Nitrous Oxide); 137-58-6 (Lidocaine); 21306-56-9 (QX-314); 6740-88-1 (Ketamine); 7361-61-7 (Xylazine)}, Sb = {IM}, Status = {MEDLINE}, Title = {A novel slow (< 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components}, Volume = {13}, Year = {1993}, url = {papers/Steriade_JNeurosci1993b.pdf}} @article{Kasanetz:2006, Abstract = {In vivo, cortical neurons and striatal medium spiny neurons (MSN) display robust subthreshold depolarizations (Up states) during which they are enabled to fire action potentials. In the cortex, Up states are believed to occur simultaneously in a neuronal ensemble and to be sustained by local network interactions. It is known that MSN are impelled into the Up state by extra-striatal (primarily cortical) inputs, but the mechanisms that sustain and determine the end of striatal Up states are still debated. Furthermore, it has not been established if brisk perturbations of ongoing cortical oscillations alter rhythmic transitions between Up and Down states in striatal neurons. Here we report that MSN Up states terminate abruptly when persistent activity in cortical ensembles providing afferents to a given striatal region is turned off by local electrical stimulation or ends spontaneously. In addition, we found that phase perturbations in MSN membrane potential slow oscillations induced by cortical stimulation replicate the stimulus-induced dynamics of spiking activity in cortical ensembles. Overall, these results suggest that striatal Up states are single-cell subthreshold representations of episodes of persistent spiking in cortical ensembles. A precise spatial and temporal alignment between episodes of cortical persistent activity and striatal Up states would allow MSN to detect specific cortical inputs embedded within a more general cortical signal.}, Address = {Departamento de Fisiologia, Facultad de Medicina, Universidad de Buenos Aires, Argentina. ferkasa@fmed.uba.ar}, Author = {Kasanetz, Fernando and Riquelme, Luis A and O'Donnell, Patricio and Murer, M Gustavo}, Crdt = {2006/08/26 09:00}, Da = {20061119}, Date = {2006 Nov 15}, Date-Added = {2009-04-08 18:11:01 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20070123}, Dep = {20060824}, Edat = {2006/08/26 09:00}, Gr = {P41 RR09754/RR/NCRR NIH HHS/United States; R03 TW6282/TW/FIC NIH HHS/United States}, Issn = {0022-3751 (Print)}, Jid = {0266262}, Journal = {J Physiol}, Jt = {The Journal of physiology}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20081120}, Mh = {Action Potentials/*physiology; Adaptation, Physiological/physiology; Animals; Biological Clocks/*physiology; Cerebral Cortex/*physiology; Corpus Striatum/*physiology; Electric Stimulation/*methods; Evoked Potentials/*physiology; Male; Neural Inhibition/*physiology; Rats; Rats, Sprague-Dawley}, Mhda = {2007/01/24 09:00}, Month = {Nov}, Number = {Pt 1}, Oid = {NLM: PMC2000673}, Own = {NLM}, Pages = {97--113}, Phst = {2006/08/24 {$[$}aheadofprint{$]$}}, Pii = {jphysiol.2006.113050}, Pl = {England}, Pmc = {PMC2000673}, pmid = {16931555}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Turning off cortical ensembles stops striatal Up states and elicits phase perturbations in cortical and striatal slow oscillations in rat in vivo}, Volume = {577}, Year = {2006}, url = {papers/Kasanetz_JPhysiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2006.113050}} @article{Valenti:2009, Abstract = {The prefrontal cortex receives multiple inputs from the hippocampal complex, which are thought to drive memory-guided behavior. Moreover, dysfunctions of both regions have been repeatedly associated with several psychiatric disorders. Therefore, understanding the interconnections and modulatory interactions between these regions is essential in evaluating their role in behavior and pathology. The effects of entorhinal cortex (EC) stimulation on the activity of identified medial prefrontal cortex (mPFC) pyramidal neurons were examined using single-unit extracellular recordings and sharp-electrode intracellular recordings in anesthetized rats. Single-pulse electrical stimulation of EC induced a powerful inhibition in the majority of mPFC neurons examined during extracellular recording. Intracellular recording showed that EC stimulation evoked a complex synaptic response, in which the greater proportion of neurons exhibited excitatory postsynaptic events and/or a short lasting and a prolonged inhibitory postsynaptic response. Furthermore, stimulation of EC selectively produced an augmentation of the bistable up-down state only in the type 2 regular spiking neurons and in a subclass of nonintrinsic bursting neurons. Taken together, these data suggest that the potent inhibition observed following EC stimulation may mask a direct excitatory response within the mPFC which markedly potentiates the bistable states in a select subpopulation of mPFC pyramidal neurons.}, Address = {University of Pittsburgh, Department of Neuroscience, Psychiatry and Psychology, Pittsburgh, PA 15260, USA. valenti@pitt.edu}, Author = {Valenti, Ornella and Grace, Anthony A}, Crdt = {2008/07/18 09:00}, Da = {20090206}, Date = {2009 Mar}, Date-Added = {2009-04-08 18:11:01 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dep = {20080716}, Edat = {2008/07/18 09:00}, Gr = {MH45156/MH/NIMH NIH HHS/United States}, Issn = {1460-2199 (Electronic)}, Jid = {9110718}, Journal = {Cereb Cortex}, Jt = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Mhda = {2008/07/18 09:00}, Mid = {NIHMS58595}, Month = {Mar}, Number = {3}, Oid = {NLM: NIHMS58595 {$[$}Available on 03/01/10{$]$}; NLM: PMC2637308 {$[$}Available on 03/01/10{$]$}}, Own = {NLM}, Pages = {658--674}, Phst = {2008/07/16 {$[$}aheadofprint{$]$}}, Pii = {bhn114}, Pl = {United States}, Pmc = {PMC2637308}, Pmcr = {2010/03/01}, pmid = {18632738}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Sb = {IM}, Status = {In-Process}, Title = {Entorhinal cortex inhibits medial prefrontal cortex and modulates the activity states of electrophysiologically characterized pyramidal neurons in vivo}, Volume = {19}, Year = {2009}, url = {papers/Valenti_CerebCortex2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhn114}} @article{Isomura:2006, Abstract = {Brain systems communicate by means of neuronal oscillations at multiple temporal and spatial scales. In anesthetized rats, we find that neocortical "slow" oscillation engages neurons in prefrontal, somatosensory, entorhinal, and subicular cortices into synchronous transitions between UP and DOWN states, with a corresponding bimodal distribution of their membrane potential. The membrane potential of hippocampal granule cells and CA3 and CA1 pyramidal cells lacked bimodality, yet it was influenced by the slow oscillation in a region-specific manner. Furthermore, in both anesthetized and naturally sleeping rats, the cortical UP states resulted in increased activity of dentate and most CA1 neurons, as well as the highest probability of ripple events. Yet, the CA3-CA1 network could self-organize into gamma bursts and occasional ripples during the DOWN state. Thus, neo/paleocortical and hippocampal networks periodically reset, self-organize, and temporally coordinate their cell assemblies via the slow oscillation.}, Address = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, New Jersey 07102, USA.}, Author = {Isomura, Yoshikazu and Sirota, Anton and Ozen, Simal and Montgomery, Sean and Mizuseki, Kenji and Henze, Darrell A and Buzsaki, Gyorgy}, Cin = {Neuron. 2006 Dec 7;52(5):748-9. PMID: 17145497}, Crdt = {2006/12/06 09:00}, Da = {20061205}, Date = {2006 Dec 7}, Date-Added = {2009-04-08 18:11:01 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20070110}, Edat = {2006/12/06 09:00}, Gr = {MH54671/MH/NIMH NIH HHS/United States; NS034994/NS/NINDS NIH HHS/United States; NS043157/NS/NINDS NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20071203}, Mh = {Anesthesia; Animals; Data Interpretation, Statistical; Electrophysiology; Entorhinal Cortex/cytology/*physiology; Extracellular Matrix/physiology; Hippocampus/cytology/*physiology; Male; Membrane Potentials/physiology; Neocortex/cytology/*physiology; Nerve Net/physiology; Neurons/physiology; Rats; Rats, Sprague-Dawley; Sleep/physiology}, Mhda = {2007/01/11 09:00}, Month = {Dec}, Number = {5}, Own = {NLM}, Pages = {871--882}, Phst = {2006/06/07 {$[$}received{$]$}; 2006/09/28 {$[$}revised{$]$}; 2006/10/24 {$[$}accepted{$]$}}, Pii = {S0896-6273(06)00822-1}, Pl = {United States}, pmid = {17145507}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Integration and segregation of activity in entorhinal-hippocampal subregions by neocortical slow oscillations}, Volume = {52}, Year = {2006}, url = {papers/Isomura_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.10.023}} @article{Nowak:2008, Abstract = {Neurons in cat area 17 can be grouped in 4 different electrophysiological cell classes (regular spiking, intrinsically bursting, chattering, and fast spiking [FS]). However, little is known of the functional properties of these different cell classes. Here we compared orientation and direction selectivity between these cell classes in cat area 17 and found that a subset of FS inhibitory neurons, usually with complex receptive fields, exhibited little selectivity in comparison with other cell types. Differences in occurrence and amplitude of gamma-range membrane fluctuations, as well as in numbers of action potentials in response to optimal visual stimuli, did not parallel differences observed for orientation and direction selectivity. Instead, differences in selectivity resulted mostly from differences in tuning of the membrane potential responses, although variations in spike threshold also contributed: weakly selective FS neurons exhibited both a lower spike threshold and more broadly tuned membrane potential responses in comparison with the other cell classes. Our results are consistent with the hypothesis that a subgroup of FS neurons receives connections and possesses intrinsic properties allowing the generation of weakly selective responses. The existence of weakly selective inhibitory neurons is consistent with orientation selectivity models that rely on broadly tuned inhibition.}, Address = {CerCo, Universite Toulouse 3, CNRS, Faculte de Medecine de Rangueil, 31062 Toulouse Cedex 9, France.}, Author = {Nowak, Lionel G and Sanchez-Vives, Maria V and McCormick, David A}, Crdt = {2007/08/28 09:00}, Da = {20080411}, Date = {2008 May}, Date-Added = {2009-04-08 18:11:01 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080611}, Dep = {20070823}, Edat = {2007/08/28 09:00}, Ein = {Cereb Cortex. 2008 Nov;18(11):2717}, Issn = {1460-2199 (Electronic)}, Jid = {9110718}, Journal = {Cereb Cortex}, Jt = {Cerebral cortex (New York, N.Y. : 1991)}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20081222}, Mh = {Action Potentials/*physiology; Animals; Cats; Cluster Analysis; Electrophysiology; Interneurons/*physiology; Models, Neurological; Neural Inhibition/*physiology; Neurons/cytology/physiology; Orientation/*physiology; Synapses/physiology; Visual Cortex/cytology/*physiology}, Mhda = {2008/06/12 09:00}, Month = {May}, Number = {5}, Own = {NLM}, Pages = {1058--1078}, Phst = {2007/08/23 {$[$}aheadofprint{$]$}}, Pii = {bhm137}, Pl = {United States}, pmid = {17720684}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Lack of orientation and direction selectivity in a subgroup of fast-spiking inhibitory interneurons: cellular and synaptic mechanisms and comparison with other electrophysiological cell types}, Volume = {18}, Year = {2008}, url = {papers/Nowak_CerebCortex2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhm137}} @article{Tononi:2006, Abstract = {During NREM sleep, neocortical neurons undergo near-synchronous transitions, every second or so, between UP states, during which they are depolarized and fire actively, and DOWN states, during which they are hyperpolarized and completely silent. In this issue of Neuron, Isomura et al. report that slow oscillations of membrane potential occur near-synchronously not only in neocortex but also in entorhinal cortex and subiculum. Within the hippocampus proper, pyramidal neurons lack the bistability of UP and DOWN states, but their firing is strongly modulated by cortical activity during the UP state. Intriguingly, many hippocampal neurons fire during the cortical DOWN state. Thus, during sleep UP states, the cortex can talk to the hippocampus, but it is unclear whether the hippocampus talks back.}, Address = {Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719, USA.}, Author = {Tononi, Giulio and Massimini, Marcello and Riedner, Brady A}, Con = {Neuron. 2006 Dec 7;52(5):871-82. PMID: 17145507}, Crdt = {2006/12/06 09:00}, Da = {20061205}, Date = {2006 Dec 7}, Date-Added = {2009-04-08 18:08:44 -0400}, Date-Modified = {2017-10-16 21:40:54 +0000}, Dcom = {20070110}, Edat = {2006/12/06 09:00}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Cortical oscillations; 21 Neurophysiology;Hippocampus;Electrophysiology;comment;Animals;Humans;Cerebral Cortex;Neurons;Sleep}, Language = {eng}, Mh = {Animals; Cerebral Cortex/*physiology; Electrophysiology; Hippocampus/*physiology; Humans; Neurons/physiology; Sleep/*physiology}, Mhda = {2007/01/11 09:00}, Month = {Dec}, Number = {5}, Own = {NLM}, Pages = {748--749}, Pii = {S0896-6273(06)00909-3}, Pl = {United States}, pmid = {17145497}, Pst = {ppublish}, Pt = {Comment; Journal Article}, Sb = {IM}, Status = {MEDLINE}, Title = {Sleepy dialogues between cortex and hippocampus: who talks to whom?}, Volume = {52}, Year = {2006}, url = {papers/Tononi_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.11.014}} @article{Hasenstaub:2005a, Abstract = {Temporal precision in spike timing is important in cortical function, interactions, and plasticity. We found that, during periods of recurrent network activity (UP states), cortical pyramidal cells in vivo and in vitro receive strong barrages of both excitatory and inhibitory postsynaptic potentials, with the inhibitory potentials showing much higher power at all frequencies above approximately 10 Hz and more synchrony between nearby neurons. Fast-spiking inhibitory interneurons discharged strongly in relation to higher-frequency oscillations in the field potential in vivo and possess membrane, synaptic, and action potential properties that are advantageous for transmission of higher-frequency activity. Intracellular injection of synaptic conductances having the characteristics of the recorded EPSPs and IPSPs reveal that IPSPs are important in controlling the timing and probability of action potential generation in pyramidal cells. Our results support the hypothesis that inhibitory networks are largely responsible for the dissemination of higher-frequency activity in cortex.}, Address = {Department of Neurobiology, Kavli Institute of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Author = {Hasenstaub, Andrea and Shu, Yousheng and Haider, Bilal and Kraushaar, Udo and Duque, Alvaro and McCormick, David A}, Crdt = {2005/08/02 09:00}, Da = {20050801}, Date = {2005 Aug 4}, Date-Added = {2009-04-08 18:08:44 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20051011}, Edat = {2005/08/02 09:00}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials/physiology; Animals; Cerebral Cortex/*physiology; *Cortical Synchronization; Excitatory Postsynaptic Potentials; Ferrets; Interneurons/physiology; Male; Membrane Potentials; Nerve Net/*physiology; Neural Inhibition/*physiology; Neurons/physiology; Oscillometry; Pyramidal Cells/physiology; Reaction Time; Refractory Period, Electrophysiological; Synapses/physiology; Synaptic Transmission/*physiology}, Mhda = {2005/10/12 09:00}, Month = {Aug}, Number = {3}, Own = {NLM}, Pages = {423--435}, Phst = {2004/12/20 {$[$}received{$]$}; 2005/04/25 {$[$}revised{$]$}; 2005/06/15 {$[$}accepted{$]$}}, Pii = {S0896-6273(05)00521-0}, Pl = {United States}, pmid = {16055065}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks}, Volume = {47}, Year = {2005}, url = {papers/Hasenstaub_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.06.016}} @article{Shu:2006a, Abstract = {Traditionally, neuronal operations in the cerebral cortex have been viewed as occurring through the interaction of synaptic potentials in the dendrite and soma, followed by the initiation of an action potential, typically in the axon. Propagation of this action potential to the synaptic terminals is widely believed to be the only form of rapid communication of information between the soma and axonal synapses, and hence to postsynaptic neurons. Here we show that the voltage fluctuations associated with dendrosomatic synaptic activity propagate significant distances along the axon, and that modest changes in the somatic membrane potential of the presynaptic neuron modulate the amplitude and duration of axonal action potentials and, through a Ca2+-dependent mechanism, the average amplitude of the postsynaptic potential evoked by these spikes. These results indicate that synaptic activity in the dendrite and soma controls not only the pattern of action potentials generated, but also the amplitude of the synaptic potentials that these action potentials initiate in local cortical circuits, resulting in synaptic transmission that is a mixture of triggered and graded (analogue) signals.}, Address = {Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.}, Author = {Shu, Yousheng and Hasenstaub, Andrea and Duque, Alvaro and Yu, Yuguo and McCormick, David A}, Cin = {Nature. 2006 Jun 8;441(7094):702-3. PMID: 16760964}, Crdt = {2006/04/21 09:00}, Da = {20060608}, Date = {2006 Jun 8}, Date-Added = {2009-04-08 18:08:44 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060713}, Dep = {20060412}, Edat = {2006/04/21 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials/physiology; Animals; Axons/physiology; Cerebral Cortex/*cytology/*physiology; Dendrites/physiology; Excitatory Postsynaptic Potentials/physiology; Ferrets/physiology; Membrane Potentials/*physiology; Neurons/cytology/*physiology; Presynaptic Terminals/physiology; Pyramidal Cells/cytology/physiology; Synapses/*physiology; Synaptic Transmission}, Mhda = {2006/07/14 09:00}, Month = {Jun}, Number = {7094}, Own = {NLM}, Pages = {761--765}, Phst = {2005/12/30 {$[$}received{$]$}; 2006/03/16 {$[$}accepted{$]$}; 2006/04/12 {$[$}aheadofprint{$]$}}, Pii = {nature04720}, Pl = {England}, pmid = {16625207}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Modulation of intracortical synaptic potentials by presynaptic somatic membrane potential}, Volume = {441}, Year = {2006}, url = {papers/Shu_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04720}} @article{Haider:2006a, Abstract = {The recurrent excitatory and inhibitory connections between and within layers of the cerebral cortex are fundamental to the operation of local cortical circuits. Models of cortical function often assume that recurrent excitation and inhibition are balanced, and we recently demonstrated that spontaneous network activity in vitro contains a precise balance of excitation and inhibition; however, the existence of a balance between excitation and inhibition in the intact and spontaneously active cerebral cortex has not been directly tested. We examined this hypothesis in the prefrontal cortex in vivo, during the slow (<1 Hz) oscillation in ketamine-xylazine-anesthetized ferrets. We measured persistent network activity (Up states) with extracellular multiple unit and local field potential recording, while simultaneously recording synaptic currents in nearby cells. We determined the reversal potential and conductance change over time during Up states and found that the body of Up state activity exhibited a steady reversal potential (-37 mV on average) for hundreds of milliseconds, even during substantial (21 nS on average) changes in membrane conductance. Furthermore, we found that both the initial and final segments of the Up state were characterized by significantly more depolarized reversal potentials and concomitant increases in excitatory conductance, compared with the stable middle portions of Up states. This ongoing temporal evolution between excitation and inhibition, which exhibits remarkable proportionality within and across neurons in active local networks, may allow for rapid transitions between relatively stable network states, permitting the modulation of neuronal responsiveness in a behaviorally relevant manner.}, Address = {Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Author = {Haider, Bilal and Duque, Alvaro and Hasenstaub, Andrea R and McCormick, David A}, Crdt = {2006/04/28 09:00}, Da = {20060427}, Date = {2006 Apr 26}, Date-Added = {2009-04-08 18:08:44 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060523}, Edat = {2006/04/28 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials/physiology; Animals; Biological Clocks/*physiology; Cells, Cultured; Computer Simulation; Excitatory Postsynaptic Potentials/*physiology; Ferrets; Male; *Models, Neurological; Neocortex/*physiology; Nerve Net/*physiology; Neural Inhibition/*physiology; Neurons/*physiology; Synaptic Transmission/physiology}, Mhda = {2006/05/24 09:00}, Month = {Apr}, Number = {17}, Own = {NLM}, Pages = {4535--4545}, Pii = {26/17/4535}, Pl = {United States}, pmid = {16641233}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition}, Volume = {26}, Year = {2006}, url = {papers/Haider_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5297-05.2006}} @article{Stein:2003, Abstract = {In the CNS, gamma-aminobutyric acid (GABA) acts as an inhibitory transmitter via ligand-gated GABA(A) receptor channels and G protein-coupled GABA(B) receptors. Both of these receptor types mediate inhibitory postsynaptic transmission throughout the nervous system. For GABA(A) receptors, this inhibitory action is associated with a hyperpolarization due to an increase in conductance to chloride ions. Previous studies show that GABA(A) receptor activation in neonatal neurons and spinal cord neurons can be excitatory. Two papers recently appeared that clearly demonstrate that GABA can have a depolarizing and excitatory action in mature cortical neurons. Here we discuss the evolving story on chloride ion homeostasis in CNS neurons and its role in the bipolar life of the GABA(A) receptor.}, Address = {Departments of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.}, Author = {Stein, Valentin and Nicoll, Roger A}, Crdt = {2003/02/11 04:00}, Da = {20030210}, Date = {2003 Feb 6}, Date-Added = {2009-04-08 15:45:01 -0400}, Date-Modified = {2009-04-08 15:45:16 -0400}, Dcom = {20030404}, Edat = {2003/02/11 04:00}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Excitatory Amino Acids/*physiology; Neural Inhibition/*physiology; Receptors, GABA-A/*physiology; gamma-Aminobutyric Acid/*physiology}, Mhda = {2003/04/05 05:00}, Month = {Feb}, Number = {3}, Own = {NLM}, Pages = {375--378}, Pii = {S0896627303000564}, Pl = {United States}, pmid = {12575946}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {23}, Rn = {0 (Excitatory Amino Acids); 0 (Receptors, GABA-A); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {GABA generates excitement}, Volume = {37}, Year = {2003}, url = {papers/Stein_Neuron2003.pdf}} @article{Rossi:2001, Abstract = {In the mammalian visual system the formation of eye-specific layers at the thalamic level depends on retinal waves of spontaneous activity, which rely on nicotinic acetylcholine receptor activation. We found that in mutant mice lacking the beta2 subunit of the neuronal nicotinic receptor, but not in mice lacking the alpha4 subunit, retinofugal projections do not segregate into eye-specific areas, both in the dorso-lateral geniculate nucleus and in the superior colliculus. Moreover, beta2-/- mice show an expansion of the binocular subfield of the primary visual cortex and a decrease in visual acuity at the cortical level but not in the retina. We conclude that the beta2 subunit of the nicotinic acetylcholine receptor is necessary for the anatomical and functional development of the visual system.}, Address = {Laboratoire de Neurobiologie Moleculaire, Centre National de la Recherche Scientifique, Unite de Recherche Associee 2182, Recepteurs et Cognition, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France.}, Author = {Rossi, F M and Pizzorusso, T and Porciatti, V and Marubio, L M and Maffei, L and Changeux, J P}, Crdt = {2001/05/10 10:00}, Da = {20010524}, Date = {2001 May 22}, Date-Added = {2009-04-06 22:45:24 -0400}, Date-Modified = {2012-08-23 17:24:00 +0000}, Dcom = {20010719}, Dep = {20010508}, Edat = {2001/05/10 10:00}, Issn = {0027-8424 (Print)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Activity-development; 21 Neurophysiology;Spontaneous activity;retinal wave paper;Acetylcholine;Nicotinic;Mice;Transgenic;activity manipulation;LGN;Superior Colliculus;optic tectum;retina;development;refinement;structural remodeling; 21 Activity-development; Neurophysiology; mouse; in vivo; visual system; visual cortex; retina; Superior Colliculus; LGN; structural remodeling; Structure-Activity Relationship; Spontaneous activity; retinal wave paper; epibatidine; Acetylcholine}, Language = {eng}, Lr = {20081120}, Mh = {Animals; Mice; Mice, Inbred C57BL; Mice, Knockout; Receptors, Nicotinic/genetics/*metabolism/physiology; Retina/physiology; Vision, Binocular/physiology; Visual Acuity/physiology; Visual Cortex/anatomy \& histology/*physiology}, Mhda = {2001/07/20 10:01}, Month = {May}, Number = {11}, Oid = {NLM: PMC33489}, Own = {NLM}, Pages = {6453--6458}, Phst = {2001/05/08 {$[$}aheadofprint{$]$}}, Pii = {101120998}, Pl = {United States}, Pmc = {PMC33489}, pmid = {11344259}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Receptors, Nicotinic); 0 (nicotinic acetylcholine receptor alpha4 subunit); 0 (nicotinic receptor alpha4beta2); 0 (nicotinic receptor beta2)}, Sb = {IM}, Status = {MEDLINE}, Title = {Requirement of the nicotinic acetylcholine receptor beta 2 subunit for the anatomical and functional development of the visual system}, Volume = {98}, Year = {2001}, url = {papers/Rossi_ProcNatlAcadSciUSA2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.101120998}} @article{Picciotto:1995, Abstract = {Nicotine affects many aspects of behaviour including learning and memory through its interaction with neuronal nicotinic acetylcholine receptors (nAChR). Functional nAChRs are pentameric proteins containing at least one type of alpha-subunit and one type of beta-subunit. The involvement of a particular neuronal nicotinic subunit in pharmacology and behaviour was examined using gene targeting to mutate beta 2, the most widely expressed nAChR subunit in the central nervous system. We report here that high-affinity binding sites for nicotine are absent from the brains of mice homozygous for the beta 2-subunit mutation. Further, electrophysiological recording from brain slices reveals that thalamic neurons from these mice do not respond to nicotine application. Finally, behavioural tests demonstrate that nicotine no longer augments the performance of beta 2-1- mice on passive avoidance, a test of associative memory. Paradoxically, mutant mice are able to perform better than their non-mutant siblings on this task.}, Address = {CNRS UA D1284 Neurobiologie Moleculaire, Institut Pasteur, Paris, France.}, Author = {Picciotto, M R and Zoli, M and Lena, C and Bessis, A and Lallemand, Y and Le Novere, N and Vincent, P and Pich, E M and Brulet, P and Changeux, J P}, Crdt = {1995/03/02 00:00}, Da = {19950330}, Date = {1995 Mar 2}, Date-Added = {2009-04-06 22:40:41 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {19950330}, Edat = {1995/03/02}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Lr = {20061115}, Mh = {Animals; *Avoidance Learning/drug effects; Base Sequence; Brain/drug effects/*metabolism; Cell Line; DNA; Female; Homozygote; Hypothalamus/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular Sequence Data; Mutation; Nicotine/*pharmacology; Patch-Clamp Techniques; Receptors, Nicotinic/*deficiency/genetics/metabolism}, Mhda = {1995/03/02 00:01}, Month = {Mar}, Number = {6517}, Own = {NLM}, Pages = {65--67}, Pl = {ENGLAND}, pmid = {7870173}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Receptors, Nicotinic); 54-11-5 (Nicotine); 9007-49-2 (DNA)}, Sb = {IM}, Status = {MEDLINE}, Title = {Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain}, Volume = {374}, Year = {1995}, url = {papers/Picciotto_Nature1995.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/374065a0}} @article{Huang:2001a, Abstract = {Partial ablation of the superior colliculus (SC) at birth in hamsters compresses the retinocollicular map, increasing the amount of visual field represented at each SC location. Receptive field sizes of single SC neurons are maintained, however, preserving receptive field properties in the prelesion condition. The mechanism that allows single SC neurons to restrict the number of convergent retinal inputs and thus compensate for induced brain damage is unknown. In this study, we examined the role of N-methyl-D-aspartate (NMDA) receptors in controlling retinocollicular convergence. We found that chronic 2-amino-5-phosphonovaleric acid (APV) blockade of NMDA receptors from birth in normal hamsters resulted in enlarged single-unit receptive fields in SC neurons from normal maps and further enlargement in lesioned animals with compressed maps. The effect was linearly related to lesion size. These results suggest that NMDA receptors are necessary to control afferent/target convergence in the normal SC and to compensate for excess retinal afferents in lesioned animals. Despite the alteration in receptive field size in the APV-treated animals, a complete visual map was present in both normal and lesioned hamsters. Visual responsiveness in the treated SC was normal; thus the loss of compensatory plasticity was not due to reduced visual responsiveness. Our results argue that NMDA receptors are essential for map refinement, construction of receptive fields, and compensation for damage but not overall map compression. The results are consistent with a role for the NMDA receptor as a coincidence detector with a threshold, providing visual neurons with the ability to calculate the amount of visual space represented by competing retinal inputs through the absolute amount of coincidence in their firing patterns. This mechanism of population matching is likely to be of general importance during nervous system development.}, Address = {Graduate Program in Neurobiology and Behavior, Department of Biology, Georgia State University, 24 Peachtree Center Ave., Atlanta, GA 30303, USA.}, Author = {Huang, L and Pallas, S L}, Crdt = {2001/09/06 10:00}, Da = {20010905}, Date = {2001 Sep}, Date-Added = {2009-04-06 21:29:22 -0400}, Date-Modified = {2009-04-06 21:34:10 -0400}, Dcom = {20011204}, Edat = {2001/09/06 10:00}, Gr = {R01 EY-12696/EY/NEI NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {2-Amino-5-phosphonovalerate/*pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology; Animals; Animals, Newborn; Brain Mapping; Cricetinae; Electrophysiologic Techniques, Cardiac; Excitatory Amino Acid Agonists/pharmacology; Excitatory Amino Acid Antagonists/*pharmacology; Mesocricetus; N-Methylaspartate/pharmacology; Neuronal Plasticity/*drug effects/physiology; Photic Stimulation; Receptors, N-Methyl-D-Aspartate/antagonists \& inhibitors/*physiology; Superior Colliculi/growth \& development/*physiology; Visual Fields/physiology; Visual Pathways/growth \& development/physiology; Visual Perception/physiology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology}, Mhda = {2002/01/05 10:01}, Month = {Sep}, Number = {3}, Own = {NLM}, Pages = {1179--1194}, Pl = {United States}, pmid = {11535668}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Excitatory Amino Acid Agonists); 0 (Excitatory Amino Acid Antagonists); 0 (Receptors, N-Methyl-D-Aspartate); 115066-14-3 (6-Cyano-7-nitroquinoxaline-2,3-dione); 6384-92-5 (N-Methylaspartate); 76726-92-6 (2-Amino-5-phosphonovalerate); 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {NMDA antagonists in the superior colliculus prevent developmental plasticity but not visual transmission or map compression}, Volume = {86}, Year = {2001}, url = {papers/Huang_JNeurophysiol2001.pdf}} @article{Mizuno:2007, Abstract = {Neuronal activity plays a pivotal role in shaping neuronal wiring. We investigated the role of neuronal activity in the formation of interhemispheric (callosal) axon projections in neonatal mouse visual cortex. Axonal labeling with enhanced green fluorescent protein (GFP) was used to demonstrate spatially organized pattern of callosal projections: GFP-labeled callosal axons from one hemisphere projected densely to a narrowly restricted region at the border between areas 17 and 18 in the contralateral hemisphere, in which they terminated in layers 1-3 and 5. This region- and layer-specific innervation pattern developed by postnatal day 15 (P15). To explore the role of neuronal activity of presynaptic and postsynaptic neurons in callosal connection development, an inwardly rectifying potassium channel, Kir2.1, was expressed in callosal projection neurons and their target postsynaptic neurons. Kir2.1 overexpression reduced the firing rate of cortical neurons. Kir2.1 overexpression in callosal projection neurons disturbed the growth of axons and their arbors that normally occurs between P7 and P13, whereas that in postsynaptic neurons had limited effect on the pattern of presynaptic callosal axon innervation. In addition, exogenous expression of a gain-of-function Kir2.1 mutant channel found in patients with a familial heart disease caused severe deficits in callosal axon projections. These results suggest that projection neuron activity plays a crucial role in interhemispheric connection development and that enhanced Kir2.1 activity can affect cortical wiring.}, Address = {Department of Biophysics, Kyoto University Graduate School of Science, Kitashirakawa-Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan.}, Author = {Mizuno, Hidenobu and Hirano, Tomoo and Tagawa, Yoshiaki}, Cin = {J Neurosci. 2007 Oct 10;27(41):10922-3. PMID: 17928433}, Crdt = {2007/06/22 09:00}, Da = {20070621}, Date = {2007 Jun 20}, Date-Added = {2009-04-06 18:12:46 -0400}, Date-Modified = {2012-11-13 16:34:13 +0000}, Dcom = {20070719}, Edat = {2007/06/22 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology; 23 Technique;development;Neocortex;activity manipulation;frontiers review; next; toread; Grants}, Language = {eng}, Lr = {20071029}, Mh = {Animals; Animals, Newborn; Female; Gene Transfer Techniques; Mice; Mice, Inbred ICR; Nerve Net/embryology/*growth \& development; Neurons/*physiology; Pregnancy; Visual Cortex/embryology/*growth \& development; Visual Pathways/embryology/*growth \& development}, Mhda = {2007/07/20 09:00}, Month = {Jun}, Number = {25}, Own = {NLM}, Pages = {6760--6770}, Pii = {27/25/6760}, Pl = {United States}, pmid = {17581963}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {J Neurosci. 2007 Jun 20;27(25):6760-70.}, Status = {MEDLINE}, Title = {Evidence for activity-dependent cortical wiring: formation of interhemispheric connections in neonatal mouse visual cortex requires projection neuron activity}, Volume = {27}, Year = {2007}, url = {papers/Mizuno_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1215-07.2007}} @article{Hua:2005, Abstract = {The formation of functional neural networks requires precise regulation of the growth and branching of the terminal arbors of axons, processes known to be influenced by early network electrical activity. Here we show that a rule of activity-based competition between neighbouring axons appears to govern the growth and branching of retinal ganglion cell (RGC) axon arbors in the developing optic tectum of zebrafish. Mosaic expression of an exogenous potassium channel or a dominant-negative SNARE protein was used to suppress electrical or neurosecretory activity in subsets of RGC axons. Imaging in vivo showed that these forms of activity suppression strongly inhibit both net growth and the formation of new branches by individually transfected RGC axon arbors. The inhibition is relieved when the activity of nearby 'competing' RGC axons is also suppressed. These results therefore identify a new form of activity-based competition rule that might be a key regulator of axon growth and branch initiation.}, Address = {Department of Molecular and Cellular Physiology, Stanford University, Stanford, California 94305, USA. huayy@stanford.edu}, Author = {Hua, Jackie Yuanyuan and Smear, Matthew C and Baier, Herwig and Smith, Stephen J}, Cin = {Nature. 2005 Apr 21;434(7036):969. PMID: 15846331}, Crdt = {2005/04/23 09:00}, Da = {20050422}, Date = {2005 Apr 21}, Date-Added = {2009-04-06 18:12:46 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20050503}, Edat = {2005/04/23 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology; 23 Technique;Cooperative Behavior;Competitive Behavior;development;Zebrafish;frontiers review}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Axons/*physiology; Brain/cytology/growth \& development; Calcium/metabolism; Calcium Signaling; Cell Movement; Cell Shape; Humans; Membrane Proteins/genetics/metabolism; Models, Neurological; Nerve Net/*cytology/*growth \& development; Potassium Channels, Inwardly Rectifying/genetics/metabolism; Presynaptic Terminals/metabolism; R-SNARE Proteins; Retinal Ganglion Cells/*cytology/physiology; Zebrafish/embryology/genetics}, Mhda = {2005/05/04 09:00}, Month = {Apr}, Number = {7036}, Own = {NLM}, Pages = {1022--1026}, Phst = {2004/04/21 {$[$}received{$]$}; 2005/01/28 {$[$}accepted{$]$}}, Pii = {nature03409}, Pl = {England}, pmid = {15846347}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Kir2.1 channel); 0 (Membrane Proteins); 0 (Potassium Channels, Inwardly Rectifying); 0 (R-SNARE Proteins); 7440-70-2 (Calcium)}, Sb = {IM}, Source = {Nature. 2005 Apr 21;434(7036):1022-6.}, Status = {MEDLINE}, Title = {Regulation of axon growth in vivo by activity-based competition}, Volume = {434}, Year = {2005}, url = {papers/Hua_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03409}} @article{Burrone:2002a, Abstract = {The rules by which neuronal activity causes long-term modification of synapses in the central nervous system are not fully understood. Whereas competitive or correlation-based rules result in local modification of synapses, homeostatic modifications allow neuron-wide changes in synaptic strength, promoting stability. Experimental investigations of these rules at central nervous system synapses have relied generally on manipulating activity in populations of neurons. Here, we investigated the effect of suppressing excitability in single neurons within a network of active hippocampal neurons by overexpressing an inward-rectifier potassium channel. Reducing activity in a neuron before synapse formation leads to a reduction in functional synaptic inputs to that neuron; no such reduction was observed when activity of all neurons was uniformly suppressed. In contrast, suppressing activity in a single neuron after synapses are established results in a homeostatic increase in synaptic input, which restores the activity of the neuron to control levels. Our results highlight the differences between global and selective suppression of activity, as well as those between early and late manipulation of activity.}, Address = {Department of Molecular \& Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.}, Author = {Burrone, Juan and O'Byrne, Michael and Murthy, Venkatesh N}, Crdt = {2002/12/03 04:00}, Da = {20021202}, Date = {2002 Nov 28}, Date-Added = {2009-04-06 18:12:46 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20021227}, Edat = {2002/12/03 04:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology; 23 Technique; plasticity; activity manipulation; Tetrodotoxin/pharmacology; synapse formation; Electrophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials/drug effects; Cells, Cultured; Excitatory Postsynaptic Potentials/drug effects/physiology; Hippocampus/cytology/drug effects/physiology; Homeostasis; Humans; *Neural Inhibition/drug effects; *Neuronal Plasticity; Neurons/drug effects/*physiology; Patch-Clamp Techniques; Potassium Channels, Inwardly Rectifying/genetics/metabolism; Synapses/drug effects/metabolism; Tetrodotoxin/pharmacology}, Mhda = {2002/12/28 04:00}, Month = {Nov}, Number = {6914}, Own = {NLM}, Pages = {414--418}, Phst = {2002/07/16 {$[$}received{$]$}; 2002/10/23 {$[$}accepted{$]$}}, Pii = {nature01242}, Pl = {England}, pmid = {12459783}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Potassium Channels, Inwardly Rectifying); 4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Status = {MEDLINE}, Title = {Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons}, Volume = {420}, Year = {2002}, url = {papers/Burrone_Nature2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01242}} @article{Patel:2006, Abstract = {In this study we tested the hypothesis that the 65-kDa isoform of glutamate decarboxylase (GAD(65)) mediates activity-dependent GABA synthesis as invoked by seizures in anesthetized rats. GABA synthesis was measured following acute GABA-transaminase inhibition by gabaculine using spatially localized (1)H NMR spectroscopy before and after bicuculline-induced seizures. Experiments were conducted with animals pre-treated with vigabatrin 24 h earlier in order to reduce GAD(67) protein and also with non-treated controls. GAD isoform content was quantified by immunoblotting. GABA was higher in vigabatrin-treated rats compared to non-treated controls. In vigabatrin-treated animals, GABA synthesis was 28% lower compared to controls [p < 0.05; vigabatrin-treated, 0.043 +/- 0.011 micromol/(g min); non-treated, 0.060 +/- 0.014 micromol/(g min)] and GAD(67) was 60% lower. No difference between groups was observed for GAD(65). Seizures increased GABA synthesis in both control [174%; control, 0.060 +/- 0.014 micromol/(g min) vs. seizures, 0.105 +/- 0.043 micromol/(g min)] and vigabatrin-treated rats [214%; control, 0.043 +/- 0.011 micromol/(g min); seizures, 0.092 +/- 0.018 micromol/(g min)]. GAD(67) could account for at least half of basal GABA synthesis but only 20% of the two-fold increase observed in vigabatrin-treated rats during seizures. The seizure-induced activation of GAD(65) in control cortex occurs concomitantly with a 2.3-fold increase in inorganic phosphate, known to be a potent activator of apoGAD(65)in vitro. Our results are consistent with a major role for GAD(65) in activity-dependent GABA synthesis.}, Address = {Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, Connecticut, USA. anant.patel@yale.edu}, Author = {Patel, Anant B and de Graaf, Robin A and Martin, David L and Battaglioli, Gino and Behar, Kevin L}, Crdt = {2006/03/17 09:00}, Da = {20060425}, Date = {2006 Apr}, Date-Added = {2009-04-06 13:08:30 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060608}, Dep = {20060315}, Edat = {2006/03/17 09:00}, Gr = {R01-NS34813/NS/NINDS NIH HHS/United States}, Issn = {0022-3042 (Print)}, Jid = {2985190R}, Journal = {J Neurochem}, Jt = {Journal of neurochemistry}, Keywords = {12 Interneuron development}, Language = {eng}, Lr = {20071114}, Mh = {4-Aminobutyrate Transaminase/metabolism; Animals; Anticonvulsants/pharmacology; Bicuculline/pharmacology; Blotting, Western/methods; Dose-Response Relationship, Drug; GABA Antagonists/pharmacology; Glutamate Decarboxylase/*physiology; Isoenzymes/*physiology; Magnetic Resonance Spectroscopy/methods; Male; Protein Isoforms/metabolism; Rats; Rats, Sprague-Dawley; Seizures/chemically induced/*metabolism/prevention \& control; Time Factors; Vigabatrin/pharmacology; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2006/06/09 09:00}, Month = {Apr}, Number = {2}, Own = {NLM}, Pages = {385--396}, Phst = {2006/03/15 {$[$}aheadofprint{$]$}}, Pii = {JNC3741}, Pl = {England}, pmid = {16539672}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Anticonvulsants); 0 (GABA Antagonists); 0 (Isoenzymes); 0 (Protein Isoforms); 485-49-4 (Bicuculline); 56-12-2 (gamma-Aminobutyric Acid); 60643-86-9 (Vigabatrin); EC 2.6.1.19 (4-Aminobutyrate Transaminase); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 2)}, Sb = {IM}, Status = {MEDLINE}, Title = {Evidence that GAD65 mediates increased GABA synthesis during intense neuronal activity in vivo}, Volume = {97}, Year = {2006}, url = {papers/Patel_JNeurochem2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1471-4159.2006.03741.x}} @article{Fukuda:1998, Abstract = {Glutamic acid decarboxylase (GAD), the gamma-aminobutyric acid (GABA)-synthetic enzyme, consists of two isoforms, GAD67 and GAD65. Although distributions of the two GAD isoforms at the somatic level are known to be heterogeneous among different subpopulations of GABAergic neurons, those at the synaptic level have not been investigated. In order to analyze quantitatively the two GAD-isoform immunoreactivities in axon terminals, we combined confocal laser scanning microscopy with digitized image analysis to measure the gray levels of immunofluorescent signals for the two GAD isoforms in a large number of individual boutons in each hippocampal and dentate layer of the mouse. Synaptic boutons exhibited lamina-specific immunoreactivities against the GAD isoforms. Boutons in the principal cell layers (stratum pyramidale of the hippocampus proper and the granule cell layer of the dentate gyrus) showed more intense immunoreactivity against GAD67 than those in the dendritic layers (strata lacunosum-moleculare, radiatum, and oriens of the hippocampus proper and the molecular layer of the dentate gyrus). By contrast, boutons in the dendritic layers showed more intense immunoreactivity against GAD65 than those in the principal cell layers. Such differential distributions could be correlated to the GAD-isoform immunoreactivities in the axon terminals originating from parvalbumin-containing neurons, a particular subpopulation of hippocampal GABAergic neurons mainly innervating the perisomatic domain of principal neurons. In addition to previously reported physiological and pharmacological differences between the GABAergic synapses on perisomatic domain and those on distal dendrites, the present results suggest a functional differentiation of GABAergic synapses between these two inhibitory sites.}, Address = {Department of Anatomy and Neurobiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. fukuda@a3rd.med.kyushu-u.ac.jp}, Author = {Fukuda, T and Aika, Y and Heizmann, C W and Kosaka, T}, Crdt = {1998/05/29 02:04}, Da = {19980707}, Date = {1998 Jun 1}, Date-Added = {2009-04-06 12:53:53 -0400}, Date-Modified = {2009-04-06 13:01:15 -0400}, Dcom = {19980707}, Edat = {1998/05/29 02:04}, Ein = {J Comp Neurol 1998 Sep 28;399(3):424-6}, Gr = {N01-HD-6-2915/HD/NICHD NIH HHS/United States}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Keywords = {12 Interneuron development}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Cell Count; Dendrites/*physiology/ultrastructure; Dentate Gyrus/enzymology/metabolism/ultrastructure; Glutamate Decarboxylase/*metabolism; Hippocampus/*cytology/*enzymology/ultrastructure; Image Processing, Computer-Assisted; Immunohistochemistry; Isoenzymes/*metabolism; Male; Mice; Mice, Inbred C57BL; Microscopy, Confocal; Microscopy, Immunoelectron; Presynaptic Terminals/enzymology/*physiology/ultrastructure; gamma-Aminobutyric Acid/*physiology}, Mhda = {2000/06/20 09:00}, Month = {Jun}, Number = {2}, Own = {NLM}, Pages = {177--194}, Pii = {10.1002/(SICI)1096-9861(19980601)395:2<177::AID-CNE3>3.0.CO;2-{\#}}, Pl = {UNITED STATES}, pmid = {9603371}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Isoenzymes); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase)}, Sb = {IM}, Source = {J Comp Neurol. 1998 Jun 1;395(2):177-94.}, Status = {MEDLINE}, Title = {GABAergic axon terminals at perisomatic and dendritic inhibitory sites show different immunoreactivities against two GAD isoforms, GAD67 and GAD65, in the mouse hippocampus: a digitized quantitative analysis}, Volume = {395}, Year = {1998}, url = {papers/Fukuda_JCompNeurol1998.pdf}} @article{Martin:1991, Abstract = {The apoenzyme of glutamate decarboxylase {$[$}enzyme without bound cofactor, pyridoxal 5'-phosphate (pyridoxal-P)] serves as a reservoir of inactive glutamate decarboxylase (GAD) that can be activated when additional GABA synthesis is required. We have investigated which of two molecular forms of GAD is present as apoenzyme in synaptosomes and in cortex, caudate nucleus, hippocampus, and cerebellum of rat brain. Endogenous glutamate apodecarboxylase (apoGAD) was labeled by incubating extracts of synaptosomes or punches of each region with 32P-pyridoxal-P, followed by reduction with NaBH4, to link covalently the 32P-pyridoxal-P to GAD. Proteins were separated by SDS-PAGE. Punches from all four brain regions and forebrain synaptosomes contained two forms of GAD with apparent Mrs of 63 and 65 kDa as identified by immunoblotting with four antiGAD sera. Punches and synaptosomes contained a major 32P-pyridoxal-P-labeled band with an apparent Mr of 63 kDa that was stained on immunoblots by the antiGAD serum 1440 and the monoclonal antibody GAD-6, and a minor labeled band at 65 kDa that was stained by the 1440, 6799, and K2 antisera. Synaptosomes contained remarkably few other strongly labeled proteins, but punches contained several other labeled bands. Three additional lines of evidence indicate that the labeled 63-kDa protein is apoGAD: (1) it was purified by immunoaffinity chromatography with the GAD-1 monoclonal antibody; (2) it yielded one major labeled peptide when digested with chymotrypsin, and that peptide appeared identical in peptide-mapping experiments to the labeled active-site peptide isolated from chromatographically prepared rat brain GAD; and (3) its labeling was selectively blocked by 4-deoxypyridoxine 5'-phosphate, a competitive inhibitor of the binding of pyridoxal-P to GAD.(ABSTRACT TRUNCATED AT 250 WORDS)}, Address = {Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.}, Author = {Martin, D L and Martin, S B and Wu, S J and Espina, N}, Crdt = {1991/09/01 00:00}, Da = {19911003}, Date = {1991 Sep}, Date-Added = {2009-04-06 12:53:53 -0400}, Date-Modified = {2009-04-06 13:01:15 -0400}, Dcom = {19911003}, Edat = {1991/09/01}, Gr = {MH35664/MH/NIMH NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {12 Interneuron development}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Apoenzymes/*analysis/metabolism; Brain/*enzymology; Caudate Nucleus/enzymology; Cerebellum/enzymology; Cerebral Cortex/enzymology; Chromatography, Affinity; Chymotrypsin; Glutamate Decarboxylase/*analysis/metabolism; Hippocampus/enzymology; Immunoblotting; Kinetics; Molecular Weight; Peptide Mapping; Pyridoxal Phosphate/metabolism; Rats; Synaptosomes/enzymology}, Mhda = {1991/09/01 00:01}, Month = {Sep}, Number = {9}, Own = {NLM}, Pages = {2725--2731}, Pl = {UNITED STATES}, pmid = {1880546}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Apoenzymes); 54-47-7 (Pyridoxal Phosphate); EC 3.4.21.1 (Chymotrypsin); EC 4.1.1.15 (Glutamate Decarboxylase)}, Sb = {IM}, Status = {MEDLINE}, Title = {Regulatory properties of brain glutamate decarboxylase (GAD): the apoenzyme of GAD is present principally as the smaller of two molecular forms of GAD in brain}, Volume = {11}, Year = {1991}, url = {papers/Martin_JNeurosci1991.pdf}} @article{Kash:1997, Abstract = {gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, is synthesized by two glutamate decarboxylase isoforms, GAD65 and GAD67. The separate role of the two isoforms is unknown, but differences in saturation with cofactor and subcellular localization suggest that GAD65 may provide reserve pools of GABA for regulation of inhibitory neurotransmission. We have disrupted the gene encoding GAD65 and backcrossed the mutation into the C57BL/6 strain of mice. In contrast to GAD67-/- animals, which are born with developmental abnormalities and die shortly after birth, GAD65-/- mice appear normal at birth. Basal GABA levels and holo-GAD activity are normal, but the pyridoxal 5' phosphate-inducible apo-enzyme reservoir is significantly decreased. GAD65-/- mice develop spontaneous seizures that result in increased mortality. Seizures can be precipitated by fear or mild stress. Seizure susceptibility is dramatically increased in GAD65-/- mice backcrossed into a second genetic background, the nonobese diabetic (NOD/LtJ) strain of mice enabling electroencephalogram analysis of the seizures. The generally higher basal brain GABA levels in this backcross are significantly decreased by the GAD65-/- mutation, suggesting that the relative contribution of GABA synthesized by GAD65 to total brain GABA levels is genetically determined. Seizure-associated c-fos-like immunoreactivity reveals the involvement of limbic regions of the brain. These data suggest that GABA synthesized by GAD65 is important in the dynamic regulation of neural network excitability, implicate at least one modifier locus in the NOD/LtJ strain, and present GAD65-/- animals as a model of epilepsy involving GABA-ergic pathways.}, Address = {Department of Medicine, School of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA.}, Author = {Kash, S F and Johnson, R S and Tecott, L H and Noebels, J L and Mayfield, R D and Hanahan, D and Baekkeskov, S}, Crdt = {1998/02/12 00:00}, Da = {19980115}, Date = {1997 Dec 9}, Date-Added = {2009-04-06 12:35:38 -0400}, Date-Modified = {2009-04-06 12:37:45 -0400}, Dcom = {19980115}, Edat = {1998/02/12}, Gr = {DK41822/DK/NIDDK NIH HHS/United States; NS29709/11535/NS/NINDS NIH HHS/United States}, Issn = {0027-8424 (Print)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {12 Interneuron development; 21 Epilepsy}, Language = {eng}, Lr = {20081120}, Mh = {Animals; Animals, Newborn; Brain/metabolism; Crosses, Genetic; Disease Models, Animal; Epilepsy/*enzymology/*genetics/metabolism; Female; Genes, fos; Glutamate Decarboxylase/chemistry/*deficiency/genetics; Isoenzymes/chemistry/*deficiency/genetics; Limbic System/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Inbred NOD; Mice, Knockout; Molecular Weight; Phenotype; gamma-Aminobutyric Acid/metabolism}, Mhda = {1998/02/12 00:01}, Month = {Dec}, Number = {25}, Oid = {NLM: PMC28432}, Own = {NLM}, Pages = {14060--14065}, Pl = {UNITED STATES}, Pmc = {PMC28432}, pmid = {9391152}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Isoenzymes); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase)}, Sb = {IM}, Status = {MEDLINE}, Title = {Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase}, Volume = {94}, Year = {1997}, url = {papers/Kash_ProcNatlAcadSciUSA1997.pdf}} @article{Tamamaki:2003, Abstract = {Gamma-aminobutyric acid (GABA)ergic neurons in the central nervous system regulate the activity of other neurons and play a crucial role in information processing. To assist an advance in the research of GABAergic neurons, here we produced two lines of glutamic acid decarboxylase-green fluorescence protein (GAD67-GFP) knock-in mouse. The distribution pattern of GFP-positive somata was the same as that of the GAD67 in situ hybridization signal in the central nervous system. We encountered neither any apparent ectopic GFP expression in GAD67-negative cells nor any apparent lack of GFP expression in GAD67-positive neurons in the two GAD67-GFP knock-in mouse lines. The timing of GFP expression also paralleled that of GAD67 expression. Hence, we constructed a map of GFP distribution in the knock-in mouse brain. Moreover, we used the knock-in mice to investigate the colocalization of GFP with NeuN, calretinin (CR), parvalbumin (PV), and somatostatin (SS) in the frontal motor cortex. The proportion of GFP-positive cells among NeuN-positive cells (neocortical neurons) was approximately 19.5%. All the CR-, PV-, and SS-positive cells appeared positive for GFP. The CR-, PV, and SS-positive cells emitted GFP fluorescence at various intensities characteristics to them. The proportions of CR-, PV-, and SS-positive cells among GFP-positive cells were 13.9%, 40.1%, and 23.4%, respectively. Thus, the three subtypes of GABAergic neurons accounted for 77.4% of the GFP-positive cells. They accounted for 6.5% in layer I. In accord with unidentified GFP-positive cells, many medium-sized spherical somata emitting intense GFP fluorescence were observed in layer I.}, Address = {Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan. tamamaki@mbs.med.kyoto-u.ac.jp}, Author = {Tamamaki, Nobuaki and Yanagawa, Yuchio and Tomioka, Ryohei and Miyazaki, Jun-Ichi and Obata, Kunihiko and Kaneko, Takeshi}, Copyright = {Copyright 2003 Wiley-Liss, Inc.}, Crdt = {2003/10/24 05:00}, Da = {20031023}, Date = {2003 Dec 1}, Date-Added = {2009-04-06 11:26:53 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20040115}, Edat = {2003/10/24 05:00}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Keywords = {12 Interneuron development}, Language = {eng}, Lr = {20071024}, Mh = {Animals; Blotting, Western; Calcium-Binding Protein, Vitamin D-Dependent/*analysis; Central Nervous System/*chemistry; Gene Expression; Glutamate Decarboxylase/*analysis/genetics; Green Fluorescent Proteins; Immunohistochemistry; In Situ Hybridization; Isoenzymes/*analysis/genetics; Luminescent Proteins/diagnostic use/genetics/*metabolism; Mice; Mice, Neurologic Mutants; Motor Cortex/chemistry; Neurons/chemistry; Parvalbumins/*analysis; Somatostatin/*analysis; *gamma-Aminobutyric Acid}, Mhda = {2004/01/16 05:00}, Month = {Dec}, Number = {1}, Own = {NLM}, Pages = {60--79}, Pl = {United States}, pmid = {14574680}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Calcium-Binding Protein, Vitamin D-Dependent); 0 (Isoenzymes); 0 (Luminescent Proteins); 0 (Parvalbumins); 0 (calretinin); 147336-22-9 (Green Fluorescent Proteins); 51110-01-1 (Somatostatin); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 1)}, Sb = {IM}, Source = {J Comp Neurol. 2003 Dec 1;467(1):60-79.}, Status = {MEDLINE}, Title = {Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse}, Volume = {467}, Year = {2003}, url = {papers/Tamamaki_JCompNeurol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10905}} @article{Kuwana:2003, Abstract = {To examine the role of GABA in the respiratory rhythm and pattern generation in neonatal mice, we analyzed the function of the respiratory control system of 67-kDa isoform of glutamic acid decarboxylase (GAD67)-deficient neonatal mice. In these mutant (GAD67-/-) mice, GABA levels in the brainstem were reduced to about 30% of those in wild-type (GAD67+/+) mice. In in vivo preparations, ventilatory parameters were analyzed by whole body plethysmography and electromyography of intercostal muscles. GAD67-/- mice exhibited abnormal respiratory patterns, i.e. irregular respiratory rhythm, and periodic gasp-like respiration followed by shallow breathing with short inspiratory duration and apnea. In in vitro GAD67-/- brainstem-spinal cord preparations, inspiratory C4 burst duration was shorter than that in GAD67+/+ preparations. Whole cell recordings revealed that activities of inspiratory neurons in the ventral medulla of GAD67-/- mice were characterized by a short depolarization period and a paucity of firing during the inspiratory phase. Superfusion of the in vitro GAD67-/- preparation with 10 microM GABA prolonged C4 burst duration and partly restored a normal pattern of inspiration, although the restoration was limited. These results indicate that reduced GABA levels during the perinatal period induce malfunction in the respiratory control system. We suggest that GABAergic transmission is not essential for basic respiratory rhythm generation but plays an important role in the maintenance of regular respiratory rhythm and normal inspiratory pattern in neonatal mice.}, Address = {Department of Physiology, Teikyo University School of Medicine, Kaga 2-11-1, Itabashi-ku, Tokyo 173-8605, Japan. kuwanas@med.teikyo-u.ac.jp}, Author = {Kuwana, S and Okada, Y and Sugawara, Y and Tsunekawa, N and Obata, K}, Crdt = {2003/08/05 05:00}, Da = {20030804}, Date = {2003}, Date-Added = {2009-04-06 11:26:53 -0400}, Date-Modified = {2009-04-06 11:28:01 -0400}, Dcom = {20031204}, Edat = {2003/08/05 05:00}, Issn = {0306-4522 (Print)}, Jid = {7605074}, Journal = {Neuroscience}, Jt = {Neuroscience}, Keywords = {12 Interneuron development}, Language = {eng}, Lr = {20071024}, Mh = {Animals; Animals, Newborn; Brain Stem/physiology; Electromyography; Electrophysiology; Glutamate Decarboxylase/*deficiency/*metabolism/physiology; Isoenzymes/*deficiency/*metabolism/physiology; Medulla Oblongata/metabolism/*physiology; Mice; Mice, Mutant Strains; Plethysmography; *Respiration; Spinal Cord/physiology; gamma-Aminobutyric Acid/metabolism/*physiology}, Mhda = {2003/12/05 05:00}, Number = {3}, Own = {NLM}, Pages = {861--870}, Pii = {S0306452203003385}, Pl = {United States}, pmid = {12895526}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Isoenzymes); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 1)}, Sb = {IM}, Source = {Neuroscience. 2003;120(3):861-70.}, Status = {MEDLINE}, Title = {Disturbance of neural respiratory control in neonatal mice lacking GABA synthesizing enzyme 67-kDa isoform of glutamic acid decarboxylase}, Volume = {120}, Year = {2003}} @article{Endo:2003, Abstract = {We investigated characteristics of identified GABAergic neurons in slices of the superficial superior colliculus (sSC) using transgenic mice in which green fluorescent protein (GFP) is specifically expressed in GABAergic neurons. Whole-cell patch clamp recordings and intracellular staining with biocytin revealed electrophysiological and morphological properties of GFP-positive neurons. GFP-positive neurons had a tangentially elongated wide dendritic field. In response to depolarizing current pulses, most of the GFP-positive neurons showed either of two firing properties; 55% (n=36/65) generated successive spikes with a constant firing frequency and 22% (n=14/65) showed transient burst firing at a threshold level for spike generation. These results elucidate a functional heterogeneity of GABAergic neurons, and provide fundamental information to understand the function of the GABAergic system in the sSC.}, Address = {Department of Integrative Physiology, National Institute for Physiological Sciences, Myodaiji, Okazaki 444-8585, Japan. tendo@nips.ac.jp}, Author = {Endo, Toshiaki and Yanagawa, Yuchio and Obata, Kunihiko and Isa, Tadashi}, Crdt = {2003/07/10 05:00}, Da = {20030709}, Date = {2003 Jul 31}, Date-Added = {2009-04-06 11:26:53 -0400}, Date-Modified = {2009-04-06 11:28:01 -0400}, Dcom = {20030902}, Edat = {2003/07/10 05:00}, Issn = {0304-3940 (Print)}, Jid = {7600130}, Journal = {Neurosci Lett}, Jt = {Neuroscience letters}, Keywords = {12 Interneuron development}, Language = {eng}, Lr = {20071115}, Mh = {Action Potentials/physiology; Animals; Green Fluorescent Proteins; Luminescent Proteins/biosynthesis/genetics; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Transgenic; Neurons/chemistry/*physiology; Superior Colliculi/chemistry/*physiology; gamma-Aminobutyric Acid/analysis/*physiology}, Mhda = {2003/09/03 05:00}, Month = {Jul}, Number = {1-2}, Own = {NLM}, Pages = {81--84}, Pii = {S0304394003005706}, Pl = {Ireland}, pmid = {12850553}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Luminescent Proteins); 147336-22-9 (Green Fluorescent Proteins); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Source = {Neurosci Lett. 2003 Jul 31;346(1-2):81-4.}, Status = {MEDLINE}, Title = {Characteristics of GABAergic neurons in the superficial superior colliculus in mice}, Volume = {346}, Year = {2003}} @article{Asada:1997, Abstract = {In addition to its role as an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA) is presumed to be involved in the development and plasticity of the nervous system. GABA is synthesized by glutamic acid decarboxylase (GAD), but the respective roles of its two isoforms (GAD65 and 67) have not been determined. The selective elimination of each GAD isoform by gene targeting is expected to clarify these issues. Recently we have produced GAD65 -/- mice and demonstrated that lack of GAD65 does not change brain GABA contents or animal behavior, except for a slight increase in susceptibility to seizures. Here we report the production of GAD67 -/- mice. These mice were born at the expected frequency but died of severe cleft palate during the first morning after birth. GAD activities and GABA contents were reduced to 20% and 7%, respectively, in the cerebral cortex of the newborn GAD67 -/- mice. Their brain, however, did not show any discernible defects. Previous pharmacological and genetic investigations have suggested the involvement of GABA in palate formation, but this is the first demonstration of a role for GAD67-derived GABA in the development of nonneural tissue.}, Address = {Laboratory of Neurochemistry, National Institute for Physiological Sciences, Myodaiji-cho, Okazaki 444, Japan.}, Author = {Asada, H and Kawamura, Y and Maruyama, K and Kume, H and Ding, R G and Kanbara, N and Kuzume, H and Sanbo, M and Yagi, T and Obata, K}, Crdt = {1997/06/10 00:00}, Da = {19970710}, Date = {1997 Jun 10}, Date-Added = {2009-04-06 11:26:53 -0400}, Date-Modified = {2009-04-06 11:28:01 -0400}, Dcom = {19970710}, Edat = {1997/06/10}, Issn = {0027-8424 (Print)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {12 Interneuron development}, Language = {eng}, Lr = {20081120}, Mh = {Aging/metabolism; Animals; Brain/*metabolism; Cerebral Cortex/growth \& development/metabolism; Cleft Palate/*genetics/*metabolism; Genotype; Glutamate Decarboxylase/*deficiency/genetics/metabolism; Isoenzymes/*deficiency/genetics/metabolism; Kinetics; Mice; Mice, Knockout; Mice, Neurologic Mutants; Polymerase Chain Reaction; RNA, Messenger/biosynthesis; Transcription, Genetic; gamma-Aminobutyric Acid/*metabolism}, Mhda = {1997/06/10 00:01}, Month = {Jun}, Number = {12}, Oid = {NLM: PMC21078}, Own = {NLM}, Pages = {6496--6499}, Pl = {UNITED STATES}, Pmc = {PMC21078}, pmid = {9177246}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Isoenzymes); 0 (RNA, Messenger); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase)}, Sb = {IM}, Status = {MEDLINE}, Title = {Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase}, Volume = {94}, Year = {1997}, url = {papers/Asada_ProcNatlAcadSciUSA1997.pdf}} @article{Lund:1972, Author = {Lund, J S and Lund, R D}, Crdt = {1972/07/13 00:00}, Da = {19720921}, Date = {1972 Jul 13}, Date-Added = {2009-04-05 21:05:52 -0400}, Date-Modified = {2009-04-05 21:06:47 -0400}, Dcom = {19720921}, Edat = {1972/07/13}, Issn = {0006-8993 (Print)}, Jid = {0045503}, Journal = {Brain Res}, Jt = {Brain research}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Form Perception; Rats; *Sensory Deprivation; Superior Colliculi/anatomy \& histology/*growth \& development; Synapses/*growth \& development; *Vision, Ocular; Visual Perception}, Mhda = {1972/07/13 00:01}, Month = {Jul}, Number = {1}, Own = {NLM}, Pages = {21--32}, Pii = {0006-8993(72)90039-X}, Pl = {NETHERLANDS}, pmid = {5047191}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Source = {Brain Res. 1972 Jul 13;42(1):21-32.}, Status = {MEDLINE}, Title = {The effects of varying periods of visual deprivation on synaptogenesis in the superior colliculus of the rat}, Volume = {42}, Year = {1972}, url = {papers/Lund_BrainRes1972.pdf}} @article{Lund:1972a, Author = {Lund, R D and Lund, J S}, Crdt = {1972/07/13 00:00}, Da = {19720921}, Date = {1972 Jul 13}, Date-Added = {2009-04-05 21:05:52 -0400}, Date-Modified = {2009-04-05 21:06:47 -0400}, Dcom = {19720921}, Edat = {1972/07/13}, Issn = {0006-8993 (Print)}, Jid = {0045503}, Journal = {Brain Res}, Jt = {Brain research}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Microscopy, Electron; Rats; Retina/innervation; Superior Colliculi/anatomy \& histology/*growth \& development; Synapses/*growth \& development; Visual Pathways/growth \& development}, Mhda = {1972/07/13 00:01}, Month = {Jul}, Number = {1}, Own = {NLM}, Pages = {1--20}, Pii = {0006-8993(72)90038-8}, Pl = {NETHERLANDS}, pmid = {5047186}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Status = {MEDLINE}, Title = {Development of synaptic patterns in the superior colliculus of the rat}, Volume = {42}, Year = {1972}, url = {papers/Lund_BrainRes1972a.pdf}} @article{Aamodt:2000, Abstract = {Maturation of excitatory synaptic connections depends on the amount and pattern of their activity, and activity can affect development of inhibitory synapses as well. In the superficial visual layers of the superior colliculus (sSC), developmental increases in the effectiveness of gamma-aminobutyric acid (GABA(A)) receptor-mediated inhibition may be driven by the maturation of visual inputs. In the rat sSC, GABA(A) receptor currents significantly jump in amplitude between postnatal days 17 and 18 (P17 and P18), approximately when the effects of cortical inputs are first detected in collicular neurons. We manipulated the development of these currents in vivo by implanting a drug-infused slice of the ethylene-vinyl acetate copolymer Elvax over the superior colliculus of P8 rats to chronically release from this plastic low levels of N-methyl-D-aspartate (NMDA). Sham-treated control animals received a similar implant containing only the solvent for NMDA. To examine the effects of this treatment on the development of GABA-mediated neurotransmission, we used whole cell voltage-clamp recording of spontaneous synaptic currents (sPSCs) from sSC neurons in untreated, NMDA-treated, and sham-treated superior colliculus slices ranging in age from 10 to 20 days postnatal. Both amplitude and frequency of sPSCs were studied at holding potentials of +50 mV in the presence and absence of the GABA(A) receptor antagonist, bicuculline methiodide (BMI). The normal developmental increase in GABA(A) receptor currents occurred on schedule (P18) in sham-treated sSC, but NMDA treatment caused premature up-regulation (P12). The average sPSCs in early NMDA-treated neurons were significantly larger than in age-matched sham controls or in age-matched, untreated neurons. No differences in average sPSC amplitudes across treatments or ages were present in BMI-insensitive, predominantly glutamatergic synaptic currents of the same neurons. NMDA treatment also significantly increased levels of glutamate decarboxylase (GAD), measured by quantitative western blotting with staining at P13 and P19. Cell counting using the dissector method for MAP 2 and GAD(67) at P13 and P19 indicated that the differences in GABAergic transmission were not due to increases in the proportion of inhibitory to excitatory neurons after NMDA treatment. However, chronic treatments begun at P8 with Elvax containing both NMDA and BMI significantly decreased total neuron density at P19 ( approximately 15%), suggesting that the NMDA-induced increase in GABA(A) receptor currents may protect against excitotoxicity.}, Address = {Department of Molecular Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.}, Author = {Aamodt, S M and Shi, J and Colonnese, M T and Veras, W and Constantine-Paton, M}, Crdt = {2000/03/11 09:00}, Da = {20000411}, Date = {2000 Mar}, Date-Added = {2009-04-05 20:45:26 -0400}, Date-Modified = {2009-04-05 20:45:56 -0400}, Dcom = {20000411}, Edat = {2000/03/11 09:00}, Gr = {EY-06039/EY/NEI NIH HHS/United States; NS-09569/NS/NINDS NIH HHS/United States; NS-32290/NS/NINDS NIH HHS/United States; etc.}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Aging/physiology; Animals; Carrier Proteins/metabolism; Coloring Agents; Electrophysiology; Female; GABA Plasma Membrane Transport Proteins; Glutamate Decarboxylase/metabolism; Immunohistochemistry; Lysine/analogs \& derivatives; Membrane Potentials/physiology; Membrane Proteins/metabolism; *Membrane Transport Proteins; N-Methylaspartate/*pharmacology; Neurons/ultrastructure; *Organic Anion Transporters; Patch-Clamp Techniques; Pregnancy; Rats; Rats, Sprague-Dawley; Superior Colliculi/cytology/*drug effects/physiology; gamma-Aminobutyric Acid/metabolism/*physiology}, Mhda = {2000/04/15 09:00}, Month = {Mar}, Number = {3}, Own = {NLM}, Pages = {1580--1591}, Pl = {UNITED STATES}, pmid = {10712481}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Carrier Proteins); 0 (Coloring Agents); 0 (GABA Plasma Membrane Transport Proteins); 0 (Membrane Proteins); 0 (Membrane Transport Proteins); 0 (Organic Anion Transporters); 56-12-2 (gamma-Aminobutyric Acid); 56-87-1 (Lysine); 576-19-2 (biocytin); 6384-92-5 (N-Methylaspartate); EC 4.1.1.15 (Glutamate Decarboxylase)}, Sb = {IM}, Source = {J Neurophysiol. 2000 Mar;83(3):1580-91.}, Status = {MEDLINE}, Title = {Chronic NMDA exposure accelerates development of GABAergic inhibition in the superior colliculus}, Volume = {83}, Year = {2000}, url = {papers/Aamodt_JNeurophysiol2000.pdf}} @article{Shi:1997, Abstract = {Activation of the NMDA subtype of glutamate receptor is required for activity-dependent structural plasticity in many areas of the young brain. Previous work has shown that NMDA receptor currents decline approximately at the time that developmental synaptic plasticity ends, and in situ hybridization studies have suggested that receptor subunit changes may be occurring during the same developmental interval. To establish a system in which the relationship between these properties of developing synapses can be explored, we have combined patch-clamp recordings with mRNA- and protein-level biochemical analyses to study the developmental regulation of NMDA receptors in the superficial layers of the rat superior colliculus. These experiments document an abrupt decrease in the NMDA receptor contribution to synaptic currents that occurs before eye opening and is closely associated with changes in NR1 protein, rapidly rising levels of the NMDA receptor subunit NR2A, and decreasing levels of NR2B. The functional and molecular changes also are correlated with the developmental decline in structural plasticity in these layers. In addition, both physiological and biochemical methods show evidence of GABA-mediated inhibition in the superficial collicular layers beginning after eye opening. This may provide an additional heterosynaptic mechanism for controlling excitation and plasticity in this neuropil by pattern vision. Thus our findings lend support to the idea that high levels of NMDA receptor function are associated with the potential for structural rearrangement in CNS neuropil and that the functional downregulation of this molecule results, at least partially, from changes in its subunit composition.}, Address = {Department of Biology, Yale University, New Haven, Connecticut 06520, USA.}, Author = {Shi, J and Aamodt, S M and Constantine-Paton, M}, Crdt = {1997/08/15 00:00}, Da = {19970828}, Date = {1997 Aug 15}, Date-Added = {2009-04-05 20:45:26 -0400}, Date-Modified = {2009-04-05 20:45:56 -0400}, Dcom = {19970828}, Edat = {1997/08/15}, Gr = {NS09569/NS/NINDS NIH HHS/United States; NS32290/NS/NINDS NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Age Factors; Animals; Electrophysiology; Female; Gene Expression/physiology; Neural Inhibition/physiology; Neuronal Plasticity/physiology; Pattern Recognition, Visual/physiology; Pregnancy; RNA, Messenger/metabolism; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate/chemistry/*genetics/metabolism; Superior Colliculi/chemistry/*physiology; Synaptic Transmission/*physiology; Time Factors; gamma-Aminobutyric Acid/*physiology}, Mhda = {1997/08/15 00:01}, Month = {Aug}, Number = {16}, Own = {NLM}, Pages = {6264--6276}, Pl = {UNITED STATES}, pmid = {9236237}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (RNA, Messenger); 0 (Receptors, N-Methyl-D-Aspartate); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Temporal correlations between functional and molecular changes in NMDA receptors and GABA neurotransmission in the superior colliculus}, Volume = {17}, Year = {1997}, url = {papers/Shi_JNeurosci1997.pdf}} @article{Chiu:2002, Abstract = {Utilizing a multielectrode array to record spontaneous and visually evoked activity of cortical neurons in area 17, we investigate the relationship between long-range correlated spontaneous activity and functional ocular dominance columns during early ferret postnatal development (P24-P29). In regions of visual cortex containing alternating ocular dominance patches, periodic fluctuations in correlated activity are observed in which spontaneous activity is most highly correlated between cortical patches exhibiting the same eye preference. However, these fluctuations are present even within large contralateral eye-dominated bands which lack any periodic alternations in ocular dominance. Thus, the organization of ocular dominance columns cannot fully account for the patterns of correlated activity we observe. Our results suggest that patterns of long-range correlated activity reflect an intrinsic periodicity of cortical connectivity that is constrained by segregated eye-specific LGN afferents.}, Address = {Interdepartmental Program in Neuroscience, Rochester, NY 14627, USA.}, Author = {Chiu, Chiayu and Weliky, Michael}, Crdt = {2002/10/02 04:00}, Da = {20020930}, Date = {2002 Sep 12}, Date-Added = {2009-04-05 14:39:03 -0400}, Date-Modified = {2013-05-21 20:36:03 +0000}, Dcom = {20021022}, Edat = {2002/10/02 04:00}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Cortical oscillations; retinal wave paper; Spontaneous activity; visual system; visual cortex; LGN; currOpinRvw}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials/*physiology; Aging/physiology; Animals; Animals, Newborn; Cell Differentiation/physiology; Evoked Potentials, Visual/*physiology; Ferrets; Functional Laterality/*physiology; Male; Neural Pathways/cytology/physiology; Neurons/cytology/*physiology; Synaptic Transmission/physiology; Vision, Binocular/physiology; Visual Cortex/cytology/*physiology; Visual Perception/physiology}, Mhda = {2002/10/31 04:00}, Month = {Sep}, Number = {6}, Own = {NLM}, Pages = {1123--1134}, Pii = {S089662730200867X}, Pl = {United States}, pmid = {12354401}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Relationship of correlated spontaneous activity to functional ocular dominance columns in the developing visual cortex}, Volume = {35}, Year = {2002}, url = {papers/Chiu_Neuron2002.pdf}} @article{Mooney:1996, Abstract = {Before vision, retinal ganglion cells produce spontaneous waves of action potentials. A crucial question is whether this spontaneous activity is transmitted to lateral geniculate nucleus (LGN) neurons. Using a novel in vitro preparation, we report that LGN neurons receive periodic barrages of postsynaptic currents from the retina that drive them to fire bursts of action potentials. Groups of LGN neurons are highly correlated in their firing. Experiments in wild-type and NMDAR1 knockout mice show that NMDA receptor activation is not necessary for firing. The transmission of the highly correlated retinal activity to the LGN supports the hypothesis that retinal waves drive retinogeniculate synaptic remodeling. Because LGN neurons are driven to fire action potentials, this spontaneous activity could also act more centrally to influence synaptic modification within the developing visual cortex.}, Address = {Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA.}, Author = {Mooney, R and Penn, A A and Gallego, R and Shatz, C J}, Crdt = {1996/11/01 00:00}, Da = {19970107}, Date = {1996 Nov}, Date-Added = {2009-04-05 13:59:17 -0400}, Date-Modified = {2012-04-13 18:43:57 +0000}, Dcom = {19970107}, Edat = {1996/11/01}, Gr = {GM 07365/GM/NIGMS NIH HHS/United States; MH48108/MH/NIMH NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology; retinal wave paper}, Language = {eng}, Lr = {20071114}, Mh = {2-Amino-5-phosphonovalerate/pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology; Action Potentials/drug effects/physiology; Anesthetics/pharmacology; Animals; Evoked Potentials, Visual/physiology; Excitatory Amino Acid Antagonists/pharmacology; Geniculate Bodies/*cytology; Mice; Mice, Inbred BALB C; Mice, Knockout; Neurons/chemistry/physiology; Receptors, AMPA/physiology; Receptors, N-Methyl-D-Aspartate/physiology; Retina/*cytology; Retinal Ganglion Cells/physiology; Visual Pathways}, Mhda = {1996/11/01 00:01}, Month = {Nov}, Number = {5}, Own = {NLM}, Pages = {863-874}, Pii = {S0896-6273(00)80218-4}, Pl = {UNITED STATES}, pmid = {8938119}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Anesthetics); 0 (Excitatory Amino Acid Antagonists); 0 (Receptors, AMPA); 0 (Receptors, N-Methyl-D-Aspartate); 115066-14-3 (6-Cyano-7-nitroquinoxaline-2,3-dione); 76726-92-6 (2-Amino-5-phosphonovalerate)}, Sb = {IM}, Status = {MEDLINE}, Title = {Thalamic relay of spontaneous retinal activity prior to vision}, Volume = {17}, Year = {1996}, url = {papers/Mooney_Neuron1996.pdf}} @article{Hanganu:2007, Abstract = {Acetylcholine (ACh) is known to shape the adult neocortical activity related to behavioral states and processing of sensory information. However, the impact of cholinergic input on the neonatal neuronal activity remains widely unknown. Early during development, the principal activity pattern in the primary visual (V1) cortex is the intermittent self-organized spindle burst oscillation that can be driven by the retinal waves. Here, we assessed the relationship between this early activity pattern and the cholinergic drive by either blocking or augmenting the cholinergic input and investigating the resultant effects on the activity of the rat visual cortex during the first postnatal week in vivo. Blockade of the muscarinic receptors by intracerebroventricular, intracortical, or supracortical atropine application decreased the occurrence of V1 spindle bursts by 50%, both the retina-independent and the optic nerve-mediated spindle bursts being affected. In contrast, blockade of acetylcholine esterase with physostigmine augmented the occurrence, amplitude, and duration of V1 spindle bursts. Whereas direct stimulation of the cholinergic basal forebrain nuclei increased the occurrence probability of V1 spindle bursts, their chronic immunotoxic lesion using 192 IgG-saporin decreased the occurrence of neonatal V1 oscillatory activity by 87%. Thus, the cholinergic input facilitates the neonatal V1 spindle bursts and may prime the developing cortex to operate specifically on relevant early (retinal waves) and later (visual input) stimuli.}, Address = {Institut de Neurobiologie de la Mediterranee, Institut National de la Sante et de la Recherche Medicale U29, 13273 Marseille, France. hanganu@uni-mainz.de}, Author = {Hanganu, Ileana L and Staiger, Jochen F and Ben-Ari, Yehezkel and Khazipov, Rustem}, Crdt = {2007/05/25 09:00}, Da = {20070524}, Date = {2007 May 23}, Date-Added = {2009-04-05 13:13:42 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20070622}, Edat = {2007/05/25 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Cortical oscillations}, Language = {eng}, Mh = {Animals; Animals, Newborn; Cholinergic Agents/*pharmacology; Cholinergic Agonists/pharmacology; Cholinergic Antagonists/pharmacology; Cholinergic Fibers/drug effects/*physiology; Male; Rats; Receptors, Muscarinic; Synaptic Transmission/drug effects/*physiology; Visual Cortex/drug effects/*growth \& development; Visual Pathways/drug effects/growth \& development}, Mhda = {2007/06/23 09:00}, Month = {May}, Number = {21}, Own = {NLM}, Pages = {5694--5705}, Pii = {27/21/5694}, Pl = {United States}, pmid = {17522314}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Cholinergic Agents); 0 (Cholinergic Agonists); 0 (Cholinergic Antagonists); 0 (Receptors, Muscarinic)}, Sb = {IM}, Status = {MEDLINE}, Title = {Cholinergic modulation of spindle bursts in the neonatal rat visual cortex in vivo}, Volume = {27}, Year = {2007}, url = {papers/Hanganu_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5233-06.2007}} @article{Zhou:2000, Abstract = {Spontaneous waves of excitation in the developing mammalian retina are mediated, to a large extent, by neurotransmission. However, it is unclear how the underlying neurotransmitter systems interact with each other to play specific roles in the formation of retinal waves at various developmental stages. In particular, it is puzzling why the waves maintain a similar propagation pattern even after underlying neurotransmitter systems have undergone drastic developmental changes. Using Ca(2+) imaging and patch clamp in a whole-mount preparation of the developing rabbit retina, we discovered two dramatic and coordinated transitions in the excitatory drive for retinal waves: one from a nicotinic to a muscarinic system, and the other from a fast cholinergic to a fast glutamatergic input. Retinal waves before the age of postnatal day 1 (P1) were blocked by nicotinic antagonists, but not by muscarinic or glutamatergic antagonists. After P3, however, the spontaneous wave, whose basic spatiotemporal pattern remained similar, was completely inhibited by muscarinic or glutamate antagonists, but not by nicotinic antagonists. We also found that the muscarinic drive, mediated primarily by M1 and M3 receptors, was particularly important for wave propagation, whereas the glutamatergic drive seemed more important for local excitation. Our results suggest (1) a novel mechanism by which a neurotransmitter system changes its functional role via a switch between two completely different classes of receptors for the same transmitter, (2) the cholinergic system plays a critical role in not only early but also late spontaneous waves, and (3) the continued participation of the cholinergic system may provide a network basis for the consistency in the overall propagation pattern of spontaneous retinal waves.}, Address = {Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. zhoujimmy@exchange.uams.edu}, Author = {Zhou, Z J and Zhao, D}, Crdt = {2000/08/31 11:00}, Da = {20000928}, Date = {2000 Sep 1}, Date-Added = {2009-04-03 20:07:59 -0400}, Date-Modified = {2011-09-21 15:14:51 -0400}, Dcom = {20000928}, Edat = {2000/08/31 11:00}, Gr = {R01 EY01894/EY/NEI NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology; Spontaneous activity; retinal wave paper; retina; visual system; Acetylcholine; Glutamate}, Language = {eng}, Lr = {20071114}, Mh = {6-Cyano-7-nitroquinoxaline-2,3-dione/*pharmacology; Aging; Animals; Animals, Newborn; Atropine/*pharmacology; Bungarotoxins/pharmacology; Calcium/physiology; Curare/*pharmacology; Dimethylphenylpiperazinium Iodide/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Fluorescent Dyes; Fura-2/analogs \& derivatives; Hexamethonium/pharmacology; Membrane Potentials/drug effects; Muscarine/pharmacology; Muscarinic Antagonists/pharmacology; Neurotransmitter Agents/*physiology; Nicotinic Antagonists/pharmacology; Patch-Clamp Techniques; Piperidines/pharmacology; Rabbits; Retina/embryology/growth \& development/*physiology; Retinal Ganglion Cells/drug effects/*physiology}, Mhda = {2000/09/30 11:01}, Month = {Sep}, Number = {17}, Own = {NLM}, Pages = {6570--6577}, Pii = {20/17/6570}, Pl = {UNITED STATES}, pmid = {10964962}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Bungarotoxins); 0 (Excitatory Amino Acid Antagonists); 0 (Fluorescent Dyes); 0 (Muscarinic Antagonists); 0 (Neurotransmitter Agents); 0 (Nicotinic Antagonists); 0 (Piperidines); 105344-37-4 (fura-2-am); 115066-14-3 (6-Cyano-7-nitroquinoxaline-2,3-dione); 300-54-9 (Muscarine); 51-55-8 (Atropine); 54-77-3 (Dimethylphenylpiperazinium Iodide); 60-26-4 (Hexamethonium); 7440-70-2 (Calcium); 8063-06-7 (Curare); 81405-11-0 (4-diphenylacetoxy-1,1-dimethylpiperidinium); 96314-98-6 (Fura-2)}, Sb = {IM}, Status = {MEDLINE}, Title = {Coordinated transitions in neurotransmitter systems for the initiation and propagation of spontaneous retinal waves}, Volume = {20}, Year = {2000}, url = {papers/Zhou_JNeurosci2000.pdf}} @article{Zhang:2006, Abstract = {GABA and glycine provide excitatory action during early development: they depolarize neurons and increase intracellular calcium concentration. As neurons mature, GABA and glycine become inhibitory. This switch from excitation to inhibition is thought to result from a shift of intracellular chloride concentration ([Cl-]i) from high to low, but in retina, measurements of [Cl-]i or chloride equilibrium potential (ECl) during development have not been made. Using the developing mouse retina, we systematically measured [Cl-]i in parallel with GABA's actions on calcium and chloride. In ganglion and amacrine cells, fura-2 imaging showed that before postnatal day (P) 6, exogenous GABA, acting via ionotropic GABA receptors, evoked calcium rise, which persisted in HCO3- -free buffer but was blocked with 0 extracellular calcium. After P6, GABA switched to inhibiting spontaneous calcium transients. Concomitant with this switch we observed the following: 6-methoxy-N-ethylquinolinium iodide (MEQ) chloride imaging showed that GABA caused an efflux of chloride before P6 and an influx afterward; gramicidin-perforated-patch recordings showed that the reversal potential for GABA decreased from -45 mV, near threshold for voltage-activated calcium channel, to -60 mV, near resting potential; MEQ imaging showed that [Cl-]i shifted steeply around P6 from 29 to 14 mM, corresponding to a decline of ECl from -39 to -58 mV. We also show that GABAergic amacrine cells became stratified by P4, potentially allowing GABA's excitatory action to shape circuit connectivity. Our results support the hypothesis that a shift from high [Cl-]i to low causes GABA to switch from excitatory to inhibitory.}, Address = {Deaprtment of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USA.}, Author = {Zhang, Ling-Li and Pathak, Hemal R and Coulter, Douglas A and Freed, Michael A and Vardi, Noga}, Crdt = {2005/12/24 09:00}, Da = {20060322}, Date = {2006 Apr}, Date-Added = {2009-04-03 20:05:32 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060925}, Dep = {20051221}, Edat = {2005/12/24 09:00}, Gr = {EY-00828/EY/NEI NIH HHS/United States; EY-11105/EY/NEI NIH HHS/United States; EY-13333/EY/NEI NIH HHS/United States; NS-32403/NS/NINDS NIH HHS/United States; NS-38572/NS/NINDS NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Action Potentials/physiology; Aging/physiology; Amacrine Cells/*metabolism; Animals; Animals, Newborn; Calcium/metabolism/pharmacology; Calcium Channels/physiology; Chlorides/*metabolism; Diagnostic Imaging/methods; Fura-2; Gramicidin; Membrane Potentials; Mice; Microscopy, Fluorescence/methods; Neural Inhibition/physiology; Patch-Clamp Techniques; Quinolinium Compounds; Receptors, GABA/physiology; Retina/*growth \& development/physiology; Retinal Ganglion Cells/*metabolism; Time Factors; gamma-Aminobutyric Acid/pharmacology/physiology}, Mhda = {2006/09/26 09:00}, Month = {Apr}, Number = {4}, Own = {NLM}, Pages = {2404--2416}, Phst = {2005/12/21 {$[$}aheadofprint{$]$}}, Pii = {00578.2005}, Pl = {United States}, pmid = {16371454}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Rn = {0 (Calcium Channels); 0 (Chlorides); 0 (Quinolinium Compounds); 0 (Receptors, GABA); 134907-10-1 (6-methoxy-N-ethylquinolinium); 1405-97-6 (Gramicidin); 56-12-2 (gamma-Aminobutyric Acid); 7440-70-2 (Calcium); 96314-98-6 (Fura-2)}, Sb = {IM}, Status = {MEDLINE}, Title = {Shift of intracellular chloride concentration in ganglion and amacrine cells of developing mouse retina}, Volume = {95}, Year = {2006}, url = {papers/Zhang_JNeurophysiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00578.2005}} @article{Lien:2006a, Abstract = {Local GABA (gamma-aminobutyric acid) circuits contribute to sensory experience-dependent refinement of neuronal connections in the developing nervous system, but whether GABAergic synapses themselves can be rapidly modified by sensory stimuli is largely unknown. Here we report that repetitive light stimuli or theta burst stimulation (TBS) of the optic nerve in the developing Xenopus retinotectal system induces long-term potentiation (LTP) of glutamatergic inputs but long-term depression (LTD) of GABAergic inputs to the same tectal neuron. The LTD is due to a reduction in presynaptic GABA release and requires activation of presynaptic NMDA (N-methyl-D-aspartate) receptors (NMDARs) and coincident high-level GABAergic activity. Thus, the presynaptic NMDAR may function as a coincidence detector for adjacent glutamatergic and GABAergic activities, leading to coordinated synaptic modification by sensory experience.}, Address = {Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California Berkeley, California 94720-3200, USA.}, Author = {Lien, Cheng-Chang and Mu, Yangling and Vargas-Caballero, Mariana and Poo, Mu-ming}, Crdt = {2006/02/14 09:00}, Da = {20060224}, Date = {2006 Mar}, Date-Added = {2009-04-03 20:05:32 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060414}, Dep = {20060212}, Edat = {2006/02/14 09:00}, Gr = {EY014949/EY/NEI NIH HHS/United States; Wellcome Trust/United Kingdom}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Calcium Signaling/drug effects/physiology; Excitatory Amino Acid Agonists/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Excitatory Postsynaptic Potentials/drug effects/physiology; Glutamic Acid/metabolism; Larva; Long-Term Synaptic Depression/drug effects/*physiology; Neural Inhibition/drug effects/physiology; Patch-Clamp Techniques; Photic Stimulation; Presynaptic Terminals/drug effects/*metabolism; Receptors, N-Methyl-D-Aspartate/*metabolism; Retina/cytology/*growth \& development/metabolism; Superior Colliculi/cytology/*growth \& development/metabolism; Synaptic Transmission/drug effects/physiology; Vision, Ocular/physiology; Visual Pathways/cytology/growth \& development/metabolism; Xenopus laevis; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2006/04/15 09:00}, Month = {Mar}, Number = {3}, Own = {NLM}, Pages = {372--380}, Phst = {2005/12/08 {$[$}received{$]$}; 2006/01/24 {$[$}accepted{$]$}; 2006/02/12 {$[$}aheadofprint{$]$}}, Pii = {nn1649}, Pl = {United States}, pmid = {16474391}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Excitatory Amino Acid Agonists); 0 (Excitatory Amino Acid Antagonists); 0 (Receptors, N-Methyl-D-Aspartate); 56-12-2 (gamma-Aminobutyric Acid); 56-86-0 (Glutamic Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Visual stimuli-induced LTD of GABAergic synapses mediated by presynaptic NMDA receptors}, Volume = {9}, Year = {2006}, url = {papers/Lien_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1649}} @article{Maffei:1990, Abstract = {The spontaneous discharges of neighboring retinal ganglion cells were recorded simultaneously in anesthetized prenatal rats between embryonic days 18 and 21. We report here that in the majority of cases the firings of neighboring retinal ganglion cells are strongly correlated during prenatal life. Correlation in the discharges of neighboring cells during development has long been suggested as a way to consolidate synaptic connections with a target cell onto which they converge, a model first proposed by Hebb. Correlation in the activities of neighboring neurons in the retina could be the basis of developmental processes such as refinement of retinotopic maps in the brain and segregation of the inputs from the two eyes.}, Address = {Istituto di Neurofisiologia, Consiglio Nazionale delle Ricerche, Italy.}, Author = {Maffei, L and Galli-Resta, L}, Crdt = {1990/04/01 00:00}, Da = {19900504}, Date = {1990 Apr}, Date-Added = {2009-04-03 16:34:17 -0400}, Date-Modified = {2013-08-27 03:02:05 +0000}, Dcom = {19900504}, Edat = {1990/04/01}, Issn = {0027-8424 (Print)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {retinal wave paper; in vivo; Rats; rodent; Embryo and Fetal Development; spontaneous activity; activity-development; Anesthesia; urethane; currOpinRvw}, Language = {eng}, Lr = {20081120}, Mh = {Animals; Cell Communication; Embryonic and Fetal Development; Fetus/physiology; Rats; Retina/*embryology/*physiology; Retinal Ganglion Cells/*physiology}, Mhda = {1990/04/01 00:01}, Month = {Apr}, Number = {7}, Oid = {NLM: PMC53791}, Own = {NLM}, Pages = {2861-2864}, Pl = {UNITED STATES}, Pmc = {PMC53791}, pmid = {2320593}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Status = {MEDLINE}, Title = {Correlation in the discharges of neighboring rat retinal ganglion cells during prenatal life}, Volume = {87}, Year = {1990}, url = {papers/Maffei_ProcNatlAcadSciUSA1990.pdf}} @article{Mu:2006, Abstract = {Sensory experience plays an instructive role in the development of the nervous system. Here we showed that visual experience can induce persistent modification of developing retinotectal circuits via spike timing-dependent plasticity (STDP). Pairing light stimuli with spiking of the tectal cell induced persistent enhancement or reduction of light-evoked responses, with a dependence on the relative timing between light stimulus and postsynaptic spiking similar to that for STDP. Using precisely timed sequential three-bar stimulation to mimic a moving bar, we showed that spike timing-dependent LTP/LTD can account for the asymmetric modification of the tectal cell receptive field induced by moving bar. Furthermore, selective inhibition of signaling mediated by brain-derived neurotrophic factor and nitric oxide, which are respectively required for light-induced LTP and LTD, interfered with moving bar-induced temporally specific changes in the tectal cell responses. Together, these findings suggest that STDP can mediate sensory experience-dependent circuit refinement in the developing nervous system.}, Address = {Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA. mpoo@uclink.berkeley.edu}, Author = {Mu, Yangling and Poo, Mu-Ming}, Cin = {Neuron. 2006 Apr 6;50(1):5-7. PMID: 16600848}, Crdt = {2006/04/08 09:00}, Da = {20060407}, Date = {2006 Apr 6}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060602}, Edat = {2006/04/08 09:00}, Gr = {EY014979/EY/NEI NIH HHS/United States; NS 36999/NS/NINDS NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {2-Amino-5-phosphonovalerate/pharmacology; Action Potentials/drug effects/*physiology/radiation effects; Animals; Carbazoles/pharmacology; Enzyme Inhibitors/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Indole Alkaloids; Long-Term Potentiation/drug effects/physiology/radiation effects; Long-Term Synaptic Depression/drug effects/physiology/radiation effects; Motion Perception/*physiology; NG-Nitroarginine Methyl Ester/pharmacology; Neuronal Plasticity/drug effects/*physiology; Neurons/drug effects/*physiology; Patch-Clamp Techniques/methods; Photic Stimulation/methods; Reaction Time/physiology; Retina/*physiology; *Superior Colliculi/cytology/physiology; Time Factors; Visual Pathways/*physiology; Xenopus laevis}, Mhda = {2006/06/03 09:00}, Month = {Apr}, Number = {1}, Own = {NLM}, Pages = {115--125}, Phst = {2005/10/11 {$[$}received{$]$}; 2006/02/02 {$[$}revised{$]$}; 2006/03/01 {$[$}accepted{$]$}}, Pii = {S0896-6273(06)00177-2}, Pl = {United States}, pmid = {16600860}, Pst = {ppublish}, Pt = {Comparative Study; In Vitro; Journal Article; Research Support, N.I.H., Extramural}, Rn = {0 (Carbazoles); 0 (Enzyme Inhibitors); 0 (Excitatory Amino Acid Antagonists); 0 (Indole Alkaloids); 50903-99-6 (NG-Nitroarginine Methyl Ester); 76726-92-6 (2-Amino-5-phosphonovalerate); 97161-97-2 (K 252)}, Sb = {IM}, Source = {Neuron. 2006 Apr 6;50(1):115-25.}, Status = {MEDLINE}, Title = {Spike timing-dependent LTP/LTD mediates visual experience-dependent plasticity in a developing retinotectal system}, Volume = {50}, Year = {2006}, url = {papers/Mu_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.03.009}} @article{Vislay-Meltzer:2006, Abstract = {The precise temporal relation between pre- and postsynaptic activity modulates the strength of synaptic connections. Despite its extensive characterization in vivo and in vitro, the degree to which spike timing-dependent plasticity can shape receptive field properties is unclear. We use in vivo patch-clamp recordings of tectal neurons in developing Xenopus tadpoles to control the precise timing of action potentials with respect to the arrival of a subset of visual inputs evoked by local light stimulation on the retina. The pattern of visual inputs onto a tectal neuron was tracked over time by rapid reverse correlation mapping of receptive fields. Spike timing-dependent potentiation or depression of a subset of synapses reliably shifts the spatial receptive fields toward or away from the trained subregion of visual space, respectively. These results demonstrate that natural patterns of activity evoked by sensory stimuli play an instructive role in the developing nervous system.}, Address = {Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA. vislay@mcb.harvard.edu}, Author = {Vislay-Meltzer, Rebecca L and Kampff, Adam R and Engert, Florian}, Cin = {Neuron. 2006 Apr 6;50(1):5-7. PMID: 16600848}, Crdt = {2006/04/08 09:00}, Da = {20060407}, Date = {2006 Apr 6}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060602}, Edat = {2006/04/08 09:00}, Gr = {R01 EY0144429-01A2/EY/NEI NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Action Potentials/physiology/radiation effects; Animals; Brain Mapping; Evoked Potentials/physiology/radiation effects; Larva; Neurons/*physiology/radiation effects; Patch-Clamp Techniques; Photic Stimulation; Retina/*physiology; Superior Colliculi/*physiology; Time Factors; Visual Fields/*physiology; Visual Pathways/*cytology; Visual Perception/physiology; Xenopus}, Mhda = {2006/06/03 09:00}, Month = {Apr}, Number = {1}, Own = {NLM}, Pages = {101--114}, Phst = {2005/10/28 {$[$}received{$]$}; 2005/12/21 {$[$}revised{$]$}; 2006/02/06 {$[$}accepted{$]$}}, Pii = {S0896-6273(06)00133-4}, Pl = {United States}, pmid = {16600859}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {Neuron. 2006 Apr 6;50(1):101-14.}, Status = {MEDLINE}, Title = {Spatiotemporal specificity of neuronal activity directs the modification of receptive fields in the developing retinotectal system}, Volume = {50}, Year = {2006}, url = {papers/Vislay-Meltzer_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.02.016}} @article{Engert:2002, Abstract = {During development of the visual system, the pattern of visual inputs may have an instructive role in refining developing neural circuits. How visual inputs of specific spatiotemporal patterns shape the circuit development remains largely unknown. We report here that, in the developing Xenopus retinotectal system, the receptive field of tectal neurons can be 'trained' to become direction-sensitive within minutes after repetitive exposure of the retina to moving bars in a particular direction. The induction of direction-sensitivity depends on the speed of the moving bar, can not be induced by random visual stimuli, and is accompanied by an asymmetric modification of the tectal neuron's receptive field. Furthermore, such training-induced changes require spiking of the tectal neuron and activation of a NMDA (N-methyl-D-aspartate) subtype of glutamate receptors during training, and are attributable to an activity-induced enhancement of glutamate-mediated inputs. Thus, developing neural circuits can be modified rapidly and specifically by visual inputs of defined spatiotemporal patterns, in a manner consistent with predictions based on spike-time-dependent synaptic modification.}, Address = {Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.}, Author = {Engert, Florian and Tao, Huizhong W and Zhang, Li I and Poo, Mu-ming}, Crdt = {2002/10/10 04:00}, Da = {20021007}, Date = {2002 Oct 3}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20021017}, Edat = {2002/10/10 04:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Motion Perception/*physiology; Neurons/*physiology; Retina/embryology/*physiology; Superior Colliculi/cytology/embryology/*physiology; Synapses; Visual Pathways; Xenopus laevis}, Mhda = {2002/10/18 04:00}, Month = {Oct}, Number = {6906}, Own = {NLM}, Pages = {470--475}, Phst = {2002/05/06 {$[$}received{$]$}; 2002/07/12 {$[$}accepted{$]$}}, Pii = {nature00988}, Pl = {England}, pmid = {12368854}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Nature. 2002 Oct 3;419(6906):470-5.}, Status = {MEDLINE}, Title = {Moving visual stimuli rapidly induce direction sensitivity of developing tectal neurons}, Volume = {419}, Year = {2002}, url = {papers/Engert_Nature2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature00988}} @article{Debski:2002, Abstract = {It is now 15 years since the discovery that N-methyl-d-aspartate receptor activity is required to maintain the refined topographic organization of retinotectal projections. Recent studies have identified additional components of the signaling pathways required for activity-dependent map formation and maintenance. Nitric oxide and brain-derived neurotrophic factor, candidate retrograde messengers, and serotonin and acetylcholine, modulators of neuronal excitability, all affect mapping. These studies indicate that the mapping process intersects with other processes fundamental to visual system development and function, such as process outgrowth, synaptic turnover and neuromodulation.}, Address = {Department of Biological Sciences, University of Kentucky, 101 Morgan Biological Science Building, Lexington, Kentucky 40506, USA.}, Author = {Debski, Elizabeth A and Cline, Hollis T}, Crdt = {2002/02/28 10:00}, Da = {20020225}, Date = {2002 Feb}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2009-04-03 13:22:16 -0400}, Dcom = {20020404}, Edat = {2002/02/28 10:00}, Issn = {0959-4388 (Print)}, Jid = {9111376}, Journal = {Curr Opin Neurobiol}, Jt = {Current opinion in neurobiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Brain Mapping; Neural Pathways/physiology; Retina/*cytology/*embryology; Superior Colliculi/*cytology/*embryology}, Mhda = {2002/04/12 10:01}, Month = {Feb}, Number = {1}, Own = {NLM}, Pages = {93--99}, Pii = {S0959438802002957}, Pl = {England}, pmid = {11861170}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {71}, Sb = {IM}, Source = {Curr Opin Neurobiol. 2002 Feb;12(1):93-9.}, Status = {MEDLINE}, Title = {Activity-dependent mapping in the retinotectal projection}, Volume = {12}, Year = {2002}, url = {papers/Debski_CurrOpinNeurobiol2002.pdf}} @article{Gnuegge:2001, Abstract = {The formation of a retinotopic map is thought to involve an activity-independent molecular phase for early steps of both axon pathfinding and projection and a later phase in which cross talk between retinal ganglion cells (RGCs) and tectal neurons modifies and refines the neuronal connections. We report that the maturation of the retinotopic map in the zebrafish tectum involves activity-dependent processes. Zebrafish larvae mutant for the gene macho (mao) lack neuronal activity in RGCs and also display an enlarged retinotectal projection field but no significant increase in single axon length. This morphological defect can be phenocopied by raising larvae under TTX-induced neural impulse blockade. The effect of activity deprivation is dependent on the developmental stage. The projection phenotype in mao as well as in the TTX-treated larvae develops between 4 and 6 d post-fertilization (dpf), after complete tectal coverage is first achieved. Electrophysiological recordings of RGCs in wild-type and mao zebrafish larvae reveal a temporally regulated reduction of sodium current in the mutant between 5 and 6 dpf. This coincides with the time of the axonal projection shifting on the tectum to compensate for the disparate growth patterns of the retina and the tectum. Our genetic and physiological analyses suggest a model in which neuronal activity in RGCs is needed for the establishment of morphological plasticity.}, Address = {Max-Planck-Institut fur Entwicklungsbiologie, 72076 Tubingen, Germany, and Zoologisches Institut, Universitat Tubingen, 72076 Tubingen, Germany.}, Author = {Gnuegge, L and Schmid, S and Neuhauss, S C}, Crdt = {2001/05/23 10:00}, Da = {20010524}, Date = {2001 May 15}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2009-04-03 13:22:16 -0400}, Dcom = {20010621}, Edat = {2001/05/23 10:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Axons/drug effects/physiology/ultrastructure; Eye Movements/drug effects/physiology; Fluorescent Dyes; Genes, Recessive; Microinjections; Mutation/*physiology; Neuronal Plasticity/drug effects/physiology; Neurons/drug effects/*physiology; Patch-Clamp Techniques; Presynaptic Terminals/physiology; Retina/cytology/drug effects/*physiology; Retinal Ganglion Cells/drug effects/physiology; Sodium/metabolism; Superior Colliculi/cytology/drug effects/*physiology; Tetrodotoxin/administration \& dosage; Visual Pathways/drug effects/growth \& development/*physiology; Zebrafish}, Mhda = {2001/06/22 10:01}, Month = {May}, Number = {10}, Own = {NLM}, Pages = {3542--3548}, Pii = {21/10/3542}, Pl = {United States}, pmid = {11331383}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {0 (Fluorescent Dyes); 4368-28-9 (Tetrodotoxin); 7440-23-5 (Sodium)}, Sb = {IM}, Source = {J Neurosci. 2001 May 15;21(10):3542-8.}, Status = {MEDLINE}, Title = {Analysis of the activity-deprived zebrafish mutant macho reveals an essential requirement of neuronal activity for the development of a fine-grained visuotopic map}, Volume = {21}, Year = {2001}, url = {papers/Gnuegge_JNeurosci2001.pdf}} @article{Constantine-Paton:1990, Address = {Department of Biology, Yale University, New Haven, Connecticut 06511.}, Author = {Constantine-Paton, M and Cline, H T and Debski, E}, Crdt = {1990/01/01 00:00}, Da = {19900524}, Date = {1990}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {19900524}, Edat = {1990/01/01}, Issn = {0147-006X (Print)}, Jid = {7804039}, Journal = {Annu Rev Neurosci}, Jt = {Annual review of neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology; retinal wave paper}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Functional Laterality/physiology; Geniculate Bodies/*growth \& development/physiology; *Neuronal Plasticity; Retina/*growth \& development/physiology; Visual Cortex/*growth \& development/physiology; Visual Pathways/physiology}, Mhda = {1990/01/01 00:01}, Own = {NLM}, Pages = {129--154}, Pl = {UNITED STATES}, pmid = {2183671}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {142}, Sb = {IM}, Source = {Annu Rev Neurosci. 1990;13:129-54.}, Status = {MEDLINE}, Title = {Patterned activity, synaptic convergence, and the NMDA receptor in developing visual pathways}, Volume = {13}, Year = {1990}, url = {papers/Constantine-Paton_AnnuRevNeurosci1990.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.ne.13.030190.001021}} @article{Scherer:1989, Abstract = {Glutamate receptors appear to play a key role in several forms of experience-dependent modification of both the strength of synapses and synaptic connectivity. In developing Xenopus frogs, the connections made by isthmotectal axons relaying visual input from the eye to the ipsilateral tectum are markedly influenced by the visual activity of contralateral retinotectal axons, and normal binocular visual input is necessary in order for the ipsilateral visuotectal map to come into register with the contralateral map. We have tested whether NMDA receptors play a role in establishment of the topographic matching of binocular maps during development. We have examined the effects of chronic treatment of tectum with either the receptor agonist NMDA or the antagonists APV or CPP applied throughout early postmetamorphic life using subpial implants of drug-impregnated elvax. Both antagonists blocked the matching of the ipsilateral map to the contralateral map, while NMDA permitted such matching. Our data therefore indicate that NMDA receptors are involved in the experience-dependent establishment of matching binocular maps during development.}, Address = {Department of Physiology, State University of New York, Buffalo 14214.}, Author = {Scherer, W J and Udin, S B}, Crdt = {1989/11/01 00:00}, Da = {19900103}, Date = {1989 Nov}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2009-04-03 13:22:16 -0400}, Dcom = {19900103}, Edat = {1989/11/01}, Gr = {EY-03470/EY/NEI NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {2-Amino-5-phosphonovalerate/*pharmacology; Animals; Anticonvulsants/pharmacology; Aspartic Acid/antagonists \& inhibitors/pharmacology; Functional Laterality; N-Methylaspartate; Piperazines/*pharmacology; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter/*physiology; Reference Values; Regression Analysis; Superior Colliculi/drug effects/*physiology; Visual Fields/*drug effects; Xenopus}, Mhda = {1989/11/01 00:01}, Month = {Nov}, Number = {11}, Own = {NLM}, Pages = {3837--3843}, Pl = {UNITED STATES}, pmid = {2573697}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Anticonvulsants); 0 (Piperazines); 0 (Receptors, N-Methyl-D-Aspartate); 0 (Receptors, Neurotransmitter); 100828-16-8 (3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid); 56-84-8 (Aspartic Acid); 6384-92-5 (N-Methylaspartate); 76726-92-6 (2-Amino-5-phosphonovalerate)}, Sb = {IM}, Source = {J Neurosci. 1989 Nov;9(11):3837-43.}, Status = {MEDLINE}, Title = {N-methyl-D-aspartate antagonists prevent interaction of binocular maps in Xenopus tectum}, Volume = {9}, Year = {1989}, url = {papers/Scherer_JNeurosci1989.pdf}} @article{Schmidt:1985, Abstract = {During regeneration of the optic nerve in goldfish, the ingrowing retinal fibers successfully seek out their correct places in the overall retinotopic projection on the tectum. Chemospecific cell-surface interactions appear to be sufficient to organize only a crude retinotopic map on the tectum during regeneration. Precise retinotopic ordering appears to be achieved via an activity-dependent stabilization of appropriate synapses and is based upon the correlated activity of neighboring ganglion cells of the same receptive-field type in the retina. Four treatments have been found to block the sharpening process: (a) blocking the activity of the ganglion cells with intraocular tetrodotoxin (TTX), (b) rearing in total darkness, (c) correlating the activation of all ganglion cells via stroboscopic illumination and (d) blocking retinotectal synaptic transmission with alpha-bungarotoxin (alphaBTX). These experiments support a role for correlated visually driven activity in sharpening the diffuse projection and suggest that this correlated activity interacts within the postsynaptic cells, probably through the summation of excitatory postsynaptic potentials (EPSPs). Other experiments support the concept that effective synapses are stabilized: a local postsynaptic block of transmission causes a local disruption in the retinotectal map. The changes that occur during this disruption suggest that each arbor can move to maximize its synaptic efficacy. In development, initial retinotectal projections are often diffuse and may undergo a similar activity-dependent sharpening. Indirect retinotectal maps, as well as auditory maps, appear to be brought into register with the direct retinotopic projections by promoting the convergence of contacts with correlated activity. A similar mechanism may drive both the formation of ocular dominance patches in fish tectum and kitten visual cortex and the segregation of different receptive-field types in the lateral geniculate nucleus. Activity-dependent synaptic stabilization may therefore be a general mechanism whereby the diffuse projections of early development are brought to the precise, mature level of organization.}, Author = {Schmidt, J T}, Crdt = {1985/06/01 00:00}, Da = {19851024}, Date = {1985 Jun}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2009-04-03 13:22:16 -0400}, Dcom = {19851024}, Edat = {1985/06/01}, Gr = {EY 03736/EY/NEI NIH HHS/United States}, Issn = {0272-4340 (Print)}, Jid = {8200709}, Journal = {Cell Mol Neurobiol}, Jt = {Cellular and molecular neurobiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Birds; Brain/growth \& development; Cats; Cell Adhesion; Chick Embryo; Cricetinae; Electrophysiology; Goldfish; Haplorhini; Models, Neurological; Neuromuscular Junction/physiology; Neuronal Plasticity; Retina/*growth \& development; Retinal Ganglion Cells/physiology; Superior Colliculi/*growth \& development; Synaptic Transmission; Tetrodotoxin/pharmacology; Visual Pathways/growth \& development; Xenopus}, Mhda = {1985/06/01 00:01}, Month = {Jun}, Number = {1-2}, Own = {NLM}, Pages = {65--84}, Pl = {UNITED STATES}, pmid = {2992788}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Source = {Cell Mol Neurobiol. 1985 Jun;5(1-2):65-84.}, Status = {MEDLINE}, Title = {Formation of retinotopic connections: selective stabilization by an activity-dependent mechanism}, Volume = {5}, Year = {1985}, url = {papers/Schmidt_CellMolNeurobiol1985.pdf}} @article{Meyer:1983, Abstract = {One optic nerve of mature goldfish was crushed in the orbit and allowed to regenerate. During regeneration impulse activity was eliminated by periodic intraocular injections of tetrodotoxin (TTX). At 32-104 days, the retinotopography of the retinotectal projection was measured autoradiographically by intraocular [3H]proline injections simultaneous with either small (10-20 degrees sector) or half retinal mapping lesions. TTX had no effect on the time-course and quality of the regeneration of gross topography seen with half retina mapping, but indefinitely inhibited higher order (refined) retinotopography normally seen by 2 months with retina sector mapping.}, Author = {Meyer, R L}, Crdt = {1983/02/01 00:00}, Da = {19830527}, Date = {1983 Feb}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2009-04-03 13:22:16 -0400}, Dcom = {19830527}, Edat = {1983/02/01}, Gr = {NS 15381/NS/NINDS NIH HHS/United States}, Issn = {0006-8993 (Print)}, Jid = {0045503}, Journal = {Brain Res}, Jt = {Brain research}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Action Potentials; Animals; Brain Mapping; Goldfish/physiology; Nerve Regeneration/*drug effects; Optic Nerve/drug effects/*physiology; Optic Nerve Injuries; Retina/*physiology; Tetrodotoxin/*pharmacology; Visual Fields}, Mhda = {1983/02/01 00:01}, Month = {Feb}, Number = {3}, Own = {NLM}, Pages = {293--298}, Pl = {NETHERLANDS}, pmid = {6831250}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Source = {Brain Res. 1983 Feb;282(3):293-8.}, Status = {MEDLINE}, Title = {Tetrodotoxin inhibits the formation of refined retinotopography in goldfish}, Volume = {282}, Year = {1983}} @article{Udin:1983, Abstract = {Throughout the normal vertebrate brain, visual maps form the left and right eyes overlap and are in register with one another. Visual input has a major role in the development of the pathways which mediate these binocular projections. A dramatic example of the developmental role of sensory input occurs in the isthmo-tectal projection, which is part of the polysynaptic relay from the eye to the ipsilateral tectum of the frog, Xenopus laevis. If one eye is rotated when the animal is still a tadpole, the isthmic axons respond by changing the topography of their terminations in the tectum; for example, a given isthmo-tectal axon which normally would connect with medial tectum can be induced to terminate in lateral tectum. Such rearrangements bring the ipsilateral visual map into register with the contralateral retinotectal map, even though one eye has been rotated. Indirect evidence has suggested that after early eye rotation, isthmo-tectal axons do not grow directly to their new tectal targets but instead reach those targets by routes which pass through their normal termination zones. Here I have used anterograde horseradish peroxidase labelling of isthmo-tectal fibres to show the trajectories of such axons and to compare them with the routes which axons take when allowed to develop normally. Tracings of individual axons in flat-mounted, unsectioned tecta show that most axons in normal Xenopus follow fairly straight paths in the tectum. In contrast, early eye rotation causes many isthmo-tectal axons to follow crooked, circuitous pathways before they terminate.}, Author = {Udin, S B}, Crdt = {1983/01/27 00:00}, Da = {19830311}, Date = {1983 Jan 27}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2009-04-03 13:22:16 -0400}, Dcom = {19830311}, Edat = {1983/01/27}, Gr = {EY 03470/EY/NEI NIH HHS/United States}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Axons/*physiology; Superior Colliculi/physiology; Visual Pathways/*physiology; Xenopus laevis/*physiology}, Mhda = {1983/01/27 00:01}, Month = {Jan}, Number = {5898}, Own = {NLM}, Pages = {336--338}, Pl = {ENGLAND}, pmid = {6823306}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Nature. 1983 Jan 27;301(5898):336-8.}, Status = {MEDLINE}, Title = {Abnormal visual input leads to development of abnormal axon trajectories in frogs}, Volume = {301}, Year = {1983}, url = {papers/Udin_Nature1983.pdf}} @article{Constantine-Paton:1978, Abstract = {An extra eye primordium was implanted into the forebrain region of embryonic Rana pipiens. During development both normal and supernumerary optic tracts terminated within a single, previously uninnervated tectal lobe. Autoradiographic tracing of either the normal or supernumerary eye's projection revealed distinct, eye-specific bands of radioactivity running rostrocaudally through the dually innervated tectum. Interactions among axons of retinal ganglion cells, possibly mediated through tectal neurons, must be invoked to explain this stereotyped disruption of the normally continuous retinal termination pattern.}, Author = {Constantine-Paton, M and Law, M I}, Crdt = {1978/11/10 00:00}, Da = {19781227}, Date = {1978 Nov 10}, Date-Added = {2009-04-03 13:19:49 -0400}, Date-Modified = {2010-11-14 10:42:51 -0800}, Dcom = {19781227}, Edat = {1978/11/10}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; 21 Neurophysiology; retinal wave paper}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Anura; Electrophysiology; Eye/transplantation; Rana pipiens; Superior Colliculi/cytology/*embryology/growth \& development; Transplantation, Homologous; Visual Pathways/*embryology/growth \& development/physiology}, Mhda = {1978/11/10 00:01}, Month = {Nov}, Number = {4368}, Own = {NLM}, Pages = {639--641}, Pl = {UNITED STATES}, pmid = {309179}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Eye-specific termination bands in tecta of three-eyed frogs}, Volume = {202}, Year = {1978}, url = {papers/Constantine-Paton_Science1978.pdf}} @article{Hebb1953, Author = {D.O. Hebb}, Date-Added = {2009-04-03 11:29:39 -0400}, Date-Modified = {2018-01-16 22:24:48 +0000}, Issn = {0950-5601}, Journal = {The British Journal of Animal Behaviour}, Number = {2}, Pages = {43 - 47}, Title = {Heredity and environment in mammalian behaviour}, Volume = {1}, Year = {1953}, url = {papers/Hebb_TheBritishJournalofAnimalBehaviour1953.pdf}, Bdsk-Url-1 = {http://www.sciencedirect.com/science/article/B7XNC-4JT84T7-2/2/e12e8878a063f329c65dba1acbe907d6}, Bdsk-Url-2 = {http://dx.doi.org/10.1016/S0950-5601(53)80053-5}} @article{Shah:2006, Abstract = {Successful suckling is vital to the survival of mammalian newborns. In many mammals, nursing behavior is triggered by maternally derived odors. Such odors may also promote the learned association of odorant cues present in the environment during nursing.}, Address = {Department of Anatomy, 1550 4th Street, MC 2722, University of California San Francisco, San Francisco, California 94158, USA. nms@ucsf.edu}, Author = {Shah, Nirao M}, Con = {Curr Biol. 2006 Oct 10;16(19):1956-61. PMID: 17027493}, Crdt = {2006/10/10 09:00}, Da = {20061009}, Date = {2006 Oct 10}, Date-Added = {2009-04-03 11:28:01 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20061129}, Edat = {2006/10/10 09:00}, Issn = {0960-9822 (Print)}, Jid = {9107782}, Journal = {Curr Biol}, Jt = {Current biology : CB}, Language = {eng}, Mh = {Animals; Animals, Suckling/physiology; Association Learning; *Behavior, Animal; *Cues; Lactation/*physiology; Odors; Pheromones/*physiology; Rabbits/*physiology}, Mhda = {2006/12/09 09:00}, Month = {Oct}, Number = {19}, Own = {NLM}, Pages = {R842-4}, Pii = {S0960-9822(06)02150-6}, Pl = {England}, pmid = {17027479}, Pst = {ppublish}, Pt = {Comment; Journal Article}, Rn = {0 (Pheromones)}, Sb = {IM}, Status = {MEDLINE}, Title = {Nursing behavior: remembrance of things past}, Volume = {16}, Year = {2006}, url = {papers/Shah_CurrBiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2006.09.001}} @article{Demir:2005, Abstract = {All animals exhibit innate behaviors that are specified during their development. Drosophila melanogaster males (but not females) perform an elaborate and innate courtship ritual directed toward females (but not males). Male courtship requires products of the fruitless (fru) gene, which is spliced differently in males and females. We have generated alleles of fru that are constitutively spliced in either the male or the female mode. We show that male splicing is essential for male courtship behavior and sexual orientation. More importantly, male splicing is also sufficient to generate male behavior in otherwise normal females. These females direct their courtship toward other females (or males engineered to produce female pheromones). The splicing of a single neuronal gene thus specifies essentially all aspects of a complex innate behavior.}, Address = {Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria.}, Author = {Demir, Ebru and Dickson, Barry J}, Cin = {Cell. 2005 Jun 3;121(5):664-6. PMID: 15935752}, Crdt = {2005/06/07 09:00}, Da = {20050606}, Date = {2005 Jun 3}, Date-Added = {2009-04-03 11:27:22 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20050719}, Edat = {2005/06/07 09:00}, Issn = {0092-8674 (Print)}, Jid = {0413066}, Journal = {Cell}, Jt = {Cell}, Language = {eng}, Lr = {20061115}, Mh = {Alleles; *Alternative Splicing; Animals; Brain/metabolism; Drosophila Proteins/*genetics/metabolism; Drosophila melanogaster/anatomy \& histology/*genetics/metabolism; Female; Gene Targeting; Male; Mutation; Nerve Tissue Proteins/*genetics/metabolism; Sequence Analysis, DNA; *Sexual Behavior, Animal; Transcription Factors/*genetics/metabolism}, Mhda = {2005/07/20 09:00}, Month = {Jun}, Number = {5}, Own = {NLM}, Pages = {785--794}, Phst = {2005/01/30 {$[$}received{$]$}; 2005/03/28 {$[$}revised{$]$}; 2005/04/13 {$[$}accepted{$]$}}, Pii = {S0092-8674(05)00407-1}, Pl = {United States}, pmid = {15935764}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {0 (Drosophila Proteins); 0 (Nerve Tissue Proteins); 0 (Transcription Factors); 0 (fru protein, Drosophila)}, Sb = {IM}, Status = {MEDLINE}, Title = {fruitless splicing specifies male courtship behavior in Drosophila}, Volume = {121}, Year = {2005}, url = {papers/Demir_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.04.027}} @book{Hebb:1949, Address = {New York}, Annote = {LDR 00775cam 22002411 4500 001 4528343 005 19860825000000.0 008 721213s1949 nyua b 000 0 eng 035 $9(DLC) 49050182 906 $a7$bcbc$corignew$du$eocip$f19$gy-gencatlg 010 $a 49050182 040 $aDLC$cDLC$dDLC 050 00 $aBF181$b.H4 082 00 $a131 100 1 $aHebb, D. O.$q(Donald Olding) 245 14 $aThe organization of behavior;$ba neuropsychological theory. 260 $aNew York,$bWiley,$c1949. 300 $axix, 335 p.$bdiagrs.$c22 cm. 490 0 $aA Wiley book in clinical psychology 504 $aBibliography: p. 305-319. 650 0 $aNeuropsychology. 991 $bc-GenColl$hBF181$i.H4$tCopy 1$wBOOKS 991 $bc-GenColl$hBF181$i.H4$p0000467117A$tCopy 2$wCCF }, Author = {Hebb, D. O}, Call-Number = {BF181}, Date-Added = {2009-04-03 10:59:28 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dewey-Call-Number = {131}, Genre = {Neuropsychology}, Library-Id = {49050182}, Publisher = {Wiley}, Series = {A Wiley book in clinical psychology}, Title = {The organization of behavior: a neuropsychological theory}, Year = {1949}, Bdsk-Url-1 = {http://books.google.com/books?id=VNetYrB8EBoC&printsec=frontcover}} @article{Chklovskii:2004, Abstract = {Current thinking about long-term memory in the cortex is focused on changes in the strengths of connections between neurons. But ongoing structural plasticity in the adult brain, including synapse formation/elimination and remodelling of axons and dendrites, suggests that memory could also depend on learning-induced changes in the cortical 'wiring diagram'. Given that the cortex is sparsely connected, wiring plasticity could provide a substantial boost in storage capacity, although at a cost of more elaborate biological machinery and slower learning.}, Address = {Cold Spring Harbour Laboratory, Cold Spring Harbour, New York 11724, USA.}, Author = {Chklovskii, D B and Mel, B W and Svoboda, K}, Crdt = {2004/10/16 09:00}, Da = {20041014}, Date = {2004 Oct 14}, Date-Added = {2009-04-02 17:36:11 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20041122}, Edat = {2004/10/16 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Lr = {20051116}, Mh = {Animals; Cerebral Cortex/anatomy \& histology/*cytology/*physiology; Humans; Memory/*physiology; Models, Neurological; Neuronal Plasticity/physiology; Neurons/cytology/physiology}, Mhda = {2004/12/16 09:00}, Month = {Oct}, Number = {7010}, Own = {NLM}, Pages = {782--788}, Pii = {nature03012}, Pl = {England}, pmid = {15483599}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {90}, Sb = {IM}, Status = {MEDLINE}, Title = {Cortical rewiring and information storage}, Volume = {431}, Year = {2004}, url = {papers/Chklovskii_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03012}} @article{Ramachandran:1995, Author = {Ramachandran, V S and Rogers-Ramachandran, D and Cobb, S}, Crdt = {1995/10/12 00:00}, Da = {19951114}, Date = {1995 Oct 12}, Date-Added = {2009-04-02 17:27:29 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {19951114}, Edat = {1995/10/12}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Lr = {20041117}, Mh = {Adult; Amputees; Humans; Middle Aged; *Phantom Limb; *Visual Perception}, Mhda = {1995/10/12 00:01}, Month = {Oct}, Number = {6549}, Own = {NLM}, Pages = {489--490}, Pl = {ENGLAND}, pmid = {7566144}, Pst = {ppublish}, Pt = {Letter}, Sb = {IM}, Source = {Nature. 1995 Oct 12;377(6549):489-90.}, Status = {MEDLINE}, Title = {Touching the phantom limb}, Volume = {377}, Year = {1995}, url = {papers/Ramachandran_Nature1995.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/377489a0}} @article{Ramachandran:1998, Abstract = {Almost everyone who has a limb amputated will experience a phantom limb--the vivid impression that the limb is not only still present, but in some cases, painful. There is now a wealth of empirical evidence demonstrating changes in cortical topography in primates following deafferentation or amputation, and this review will attempt to relate these in a systematic way to the clinical phenomenology of phantom limbs. With the advent of non-invasive imaging techniques such as MEG (magnetoencephalogram) and functional MRI, topographical reorganization can also be demonstrated in humans, so that it is now possible to track perceptual changes and changes in cortical topography in individual patients. We suggest, therefore, that these patients provide a valuable opportunity not only for exploring neural plasticity in the adult human brain but also for understanding the relationship between the activity of sensory neurons and conscious experience. We conclude with a theory of phantom limbs, some striking demonstrations of phantoms induced in normal subjects, and some remarks about the relevance of these phenomena to the question of how the brain constructs a 'body image.'}, Address = {Center for Brain and Cognition, University of California, San Diego, La Jolla 92093, USA. vramacha@ucsd.edu}, Author = {Ramachandran, V S and Hirstein, W}, Crdt = {1998/10/08 00:00}, Da = {19981021}, Date = {1998 Sep}, Date-Added = {2009-04-02 17:21:48 -0400}, Date-Modified = {2009-04-02 17:26:04 -0400}, Dcom = {19981021}, Edat = {1998/10/08}, Issn = {0006-8950 (Print)}, Jid = {0372537}, Journal = {Brain}, Jt = {Brain : a journal of neurology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Adult; Arm/abnormalities; Brain/physiology/*physiopathology; *Brain Mapping; Child; Humans; Incidence; Leg/abnormalities; Neurons, Afferent/physiology; Perception; Phantom Limb/epidemiology/*physiopathology/*psychology}, Mhda = {1998/10/08 00:01}, Month = {Sep}, Own = {NLM}, Pages = {1603--1630}, Pl = {ENGLAND}, pmid = {9762952}, Pst = {ppublish}, Pt = {Lectures; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {160}, Sb = {AIM; IM}, Source = {Brain. 1998 Sep;121 ( Pt 9):1603-30.}, Status = {MEDLINE}, Title = {The perception of phantom limbs. The D. O. Hebb lecture}, Volume = {121 ( Pt 9)}, Year = {1998}, url = {papers/Ramachandran_Brain1998.pdf}} @article{Wiesel:1963, Author = {Wiesel, T N and Hubel, D H}, Crdt = {1963/11/01 00:00}, Da = {19640401}, Date = {1963 Nov}, Date-Added = {2009-04-02 16:51:24 -0400}, Date-Modified = {2009-04-02 21:50:02 -0400}, Dcom = {19961201}, Edat = {1963/11/01}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {*BEHAVIOR, ANIMAL; *BLINDNESS; *BRAIN ELECTROPHYSIOLOGY; *CATS; *CEREBRAL CORTEX; *EXPERIMENTAL LAB STUDY; *LIGHT; *OCCIPITAL LOBE; *VISION}, Language = {eng}, Lr = {20081121}, Mh = {*Behavior, Animal; *Blindness; Brain/*physiology; *Cats; *Cerebral Cortex; *Light; *Occipital Lobe; *Research; *Vision, Ocular}, Mhda = {1963/11/01 00:01}, Month = {Nov}, Oto = {NLM}, Own = {NLM}, Pages = {1003--1017}, Pl = {UNITED STATES}, pmid = {14084161}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {OM}, Status = {MEDLINE}, Title = {Single-cell responses in striate cortex of kittens deprived of vision in one eye}, Volume = {26}, Year = {1963}, url = {papers/Wiesel_JNeurophysiol1963.pdf}} @article{Wiesel:1974, Author = {Wiesel, T N and Hubel, D H}, Crdt = {1974/12/01 00:00}, Da = {19750310}, Date = {1974 Dec 1}, Date-Added = {2009-04-02 16:44:21 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {19750310}, Edat = {1974/12/01}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Animals, Newborn/*anatomy \& histology/growth \& development; Brain Mapping; Dominance, Cerebral; Functional Laterality; Haplorhini/*anatomy \& histology; Mathematics; *Orientation; *Sensory Deprivation; *Vision, Ocular; Visual Cortex/*anatomy \& histology/growth \& development; Visual Fields; Visual Perception/physiology}, Mhda = {1974/12/01 00:01}, Month = {Dec}, Number = {3}, Own = {NLM}, Pages = {307--318}, Pl = {UNITED STATES}, pmid = {4215829}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article}, Sb = {IM}, Source = {J Comp Neurol. 1974 Dec 1;158(3):307-18.}, Status = {MEDLINE}, Title = {Ordered arrangement of orientation columns in monkeys lacking visual experience}, Volume = {158}, Year = {1974}, url = {papers/Wiesel_JCompNeurol1974.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901580306}} @article{Hubel:1965, Author = {Hubel, D H and Wiesel, T N}, Crdt = {1965/11/01 00:00}, Da = {19660814}, Date = {1965 Nov}, Date-Added = {2009-04-02 16:44:21 -0400}, Date-Modified = {2011-09-15 10:52:29 -0400}, Dcom = {19660814}, Edat = {1965/11/01}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Neurophysiology; retina; cat; sensory map; topographic map; visual cortex; neocortex; function; visual system; Binocular; monocular; bilateral}, Language = {eng}, Lr = {20031114}, Mh = {Animals; Cats; Cerebral Cortex/*physiology; Depth Perception; Oculomotor Muscles/*physiology; *Strabismus; Synapses}, Mhda = {1965/11/01 00:01}, Month = {Nov}, Number = {6}, Own = {NLM}, Pages = {1041--1059}, Pl = {UNITED STATES}, pmid = {5883731}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Status = {MEDLINE}, Title = {Binocular interaction in striate cortex of kittens reared with artificial squint}, Volume = {28}, Year = {1965}, url = {papers/Hubel_JNeurophysiol1965.pdf}} @article{Doupe:1999, Abstract = {Human speech and birdsong have numerous parallels. Both humans and songbirds learn their complex vocalizations early in life, exhibiting a strong dependence on hearing the adults they will imitate, as well as themselves as they practice, and a waning of this dependence as they mature. Innate predispositions for perceiving and learning the correct sounds exist in both groups, although more evidence of innate descriptions of species-specific signals exists in songbirds, where numerous species of vocal learners have been compared. Humans also share with songbirds an early phase of learning that is primarily perceptual, which then serves to guide later vocal production. Both humans and songbirds have evolved a complex hierarchy of specialized forebrain areas in which motor and auditory centers interact closely, and which control the lower vocal motor areas also found in nonlearners. In both these vocal learners, however, how auditory feedback of self is processed in these brain areas is surprisingly unclear. Finally, humans and songbirds have similar critical periods for vocal learning, with a much greater ability to learn early in life. In both groups, the capacity for late vocal learning may be decreased by the act of learning itself, as well as by biological factors such as the hormones of puberty. Although some features of birdsong and speech are clearly not analogous, such as the capacity of language for meaning, abstraction, and flexible associations, there are striking similarities in how sensory experience is internalized and used to shape vocal outputs, and how learning is enhanced during a critical period of development. Similar neural mechanisms may therefore be involved.}, Address = {Department of Psychiatry, University of California at San Francisco 94143, USA. ajd@phy.ucsf.edu}, Author = {Doupe, A J and Kuhl, P K}, Crdt = {1999/04/15 00:00}, Da = {19990604}, Date = {1999}, Date-Added = {2009-04-02 16:22:28 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {19990604}, Edat = {1999/04/15}, Gr = {DC00520/DC/NIDCD NIH HHS/United States; MH55987/MH/NIMH NIH HHS/United States; NS34835/NS/NINDS NIH HHS/United States; etc.}, Issn = {0147-006X (Print)}, Jid = {7804039}, Journal = {Annu Rev Neurosci}, Jt = {Annual review of neuroscience}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Brain/physiology; Humans; Learning/physiology; Perception/physiology; Speech/*physiology; Vocalization, Animal/*physiology}, Mhda = {1999/04/15 00:01}, Own = {NLM}, Pages = {567--631}, Pl = {UNITED STATES}, pmid = {10202549}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {220}, Sb = {IM}, Status = {MEDLINE}, Title = {Birdsong and human speech: common themes and mechanisms}, Volume = {22}, Year = {1999}, url = {papers/Doupe_AnnuRevNeurosci1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.22.1.567}} @article{Flavell:2008, Abstract = {Sensory experience and the resulting synaptic activity within the brain are critical for the proper development of neural circuits. Experience-driven synaptic activity causes membrane depolarization and calcium influx into select neurons within a neural circuit, which in turn trigger a wide variety of cellular changes that alter the synaptic connectivity within the neural circuit. One way in which calcium influx leads to the remodeling of synapses made by neurons is through the activation of new gene transcription. Recent studies have identified many of the signaling pathways that link neuronal activity to transcription, revealing both the transcription factors that mediate this process and the neuronal activity-regulated genes. These studies indicate that neuronal activity regulates a complex program of gene expression involved in many aspects of neuronal development, including dendritic branching, synapse maturation, and synapse elimination. Genetic mutations in several key regulators of activity-dependent transcription give rise to neurological disorders in humans, suggesting that future studies of this gene expression program will likely provide insight into the mechanisms by which the disruption of proper synapse development can give rise to a variety of neurological disorders.}, Address = {F.M. Kirby Neurobiology Center, Children's Hospital Boston, and Departments of Neurology and Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. Flavell@fas.harvard.edu}, Author = {Flavell, Steven W and Greenberg, Michael E}, Crdt = {2008/06/19 09:00}, Da = {20080618}, Date = {2008}, Date-Added = {2009-04-02 14:30:55 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080919}, Edat = {2008/06/19 09:00}, Gr = {HD18655/HD/NICHD NIH HHS/United States; NS048276/NS/NINDS NIH HHS/United States}, Issn = {0147-006X (Print)}, Jid = {7804039}, Journal = {Annu Rev Neurosci}, Jt = {Annual review of neuroscience}, Keywords = {Immediate-Early;genes;Transcription Factors;21 Activity-development;development;experience dependent plasticity;neurological disorder;calcium;synapse formation;refinement}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Cell Differentiation/genetics; Central Nervous System/embryology/growth \& development/*metabolism; Gene Expression Regulation, Developmental/*genetics; Humans; Neuronal Plasticity/*genetics; Neurons/*metabolism; Signal Transduction/*genetics; Synapses/genetics/metabolism; Transcription Factors/genetics; Transcriptional Activation/genetics}, Mhda = {2008/09/20 09:00}, Own = {NLM}, Pages = {563--590}, Pl = {United States}, pmid = {18558867}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review}, Rf = {150}, Rn = {0 (Transcription Factors)}, Sb = {IM}, Source = {Annu Rev Neurosci. 2008;31:563-90.}, Status = {MEDLINE}, Title = {Signaling mechanisms linking neuronal activity to gene expression and plasticity of the nervous system}, Volume = {31}, Year = {2008}, url = {papers/Flavell_AnnuRevNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.31.060407.125631}} @article{Leckman:2006, Abstract = {Tourette syndrome is a neurodevelopmental disorder characterized by motor and vocal tics--rapid, repetitive, stereotyped movements or vocalizations. Tourette syndrome typically has a prepubertal onset, and boys are more commonly affected than girls. Symptoms usually begin with transient bouts of simple motor tics. By age 10 years, most children are aware of nearly irresistible somatosensory urges that precede the tics. These urges likely reflect a defect in sensorimotor gating because they intrude into the child's conscious awareness and become a source of distraction and distress. A momentary sense of relief typically follows the completion of a tic. Over the course of hours, tics occur in bouts, with a regular intertic interval. Tics increase during periods of emotional excitement and fatigue. Tics can become "complex" in nature and appear to be purposeful. Tics can be willfully suppressed for brief intervals and can be evoked by the mere mention of them. Tics typically diminish during periods of goal-directed behavior, especially those that involve both heightened attention and fine motor or vocal control, as occur in musical and athletic performances. Over the course of months, tics wax and wane. New tics appear, often in response to new sources of somatosensory irritation, such as the appearance of a persistent vocal tic (a cough) following a cold. Over the course of years, tic severity typically peaks between 8 and 12 years of age. By the end of the second decade of life, many individuals are virtually tic free. Less than 20% of cases continue to experience clinically impairing tics as adults. Tics rarely occur in isolation, and other coexisting conditions--such as behavioral disinhibition, hypersensitivity to a broad range of sensory stimuli, problems with visual motor integration, procedural learning difficulties, attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder, depression, anxiety, and emotional instability--are often a greater source of impairment than the tics themselves. Emerging behavioral treatments of Tourette syndrome are based in part on an understanding of the moment-to-moment experience of somatosensory urges and motor response. With identification of specific genes of major effect and advances in our understanding of the neural circuitry of sensorimotor gating, habit formation, and procedural memory--together with insights from postmortem brain studies, in vivo brain imaging, and electrophysiologic recordings--we might be on the threshold of a deeper understanding of the phenomenology and natural history of Tourette syndrome.}, Address = {Yale Child Study Center, New Haven, CT 06510, USA. james.leckman{\char64}yale.edu}, Author = {Leckman, James F and Bloch, Michael H and Scahill, Lawrence and King, Robert A}, Crdt = {2006/09/15 09:00}, Da = {20060914}, Date = {2006 Aug}, Date-Added = {2009-04-02 14:30:55 -0400}, Date-Modified = {2009-04-02 14:30:55 -0400}, Dcom = {20061121}, Edat = {2006/09/15 09:00}, Gr = {1 R13 NS40925-01/NS/NINDS NIH HHS/United States; MH076273/MH/NIMH NIH HHS/United States; MH49351/MH/NIMH NIH HHS/United States; MH61940/MH/NIMH NIH HHS/United States; RR00125/RR/NCRR NIH HHS/United States}, Issn = {0883-0738 (Print)}, Jid = {8606714}, Journal = {J Child Neurol}, Jt = {Journal of child neurology}, Language = {eng}, Lr = {20071203}, Mh = {Adolescent; Attention Deficit Disorder with Hyperactivity/etiology; Child; Child, Preschool; *Ego; Female; Humans; Learning Disorders/etiology; Male; Obsessive-Compulsive Disorder/etiology; Tics/etiology; Tourette Syndrome/complications/*physiopathology/*psychology}, Mhda = {2006/12/09 09:00}, Month = {Aug}, Number = {8}, Own = {NLM}, Pages = {642--649}, Pl = {Canada}, pmid = {16970864}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review}, Rf = {77}, Sb = {IM}, Status = {MEDLINE}, Title = {Tourette syndrome: the self under siege}, Volume = {21}, Year = {2006}, url = {papers/Leckman_JChildNeurol2006.pdf}} @article{Robinson:2008, Abstract = {What genes and regulatory sequences contribute to the organization and functioning of neural circuits and molecular pathways in the brain that support social behavior? How does social experience interact with information in the genome to modulate brain activity? Here, we address these questions by highlighting progress that has been made in identifying and understanding two key "vectors of influence" that link genes, the brain, and social behavior: (i) Social information alters gene expression in the brain to influence behavior, and (ii) genetic variation influences brain function and social behavior. We also discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior.}, Address = {Department of Entomology, University of Illinois at Urbana-Champaign, 505 South Goodwin Avenue, Urbana, IL 61801, USA. generobi@illinois.edu}, Author = {Robinson, Gene E and Fernald, Russell D and Clayton, David F}, Crdt = {2008/11/08 09:00}, Da = {20081107}, Date = {2008 Nov 7}, Date-Added = {2009-04-02 14:18:41 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20081204}, Edat = {2008/11/08 09:00}, Gr = {NS045264/NS/NINDS NIH HHS/United States; NS34950/NS/NINDS NIH HHS/United States; R01 GM073644/GM/NIGMS NIH HHS/United States; R01 NS051820/NS/NINDS NIH HHS/United States}, Issn = {1095-9203 (Electronic)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Language = {eng}, Mh = {Animals; Brain/*physiology; Environment; Epigenesis, Genetic; Evolution; Gene Expression; *Genes; Genetic Variation; Genotype; Humans; *Social Behavior}, Mhda = {2008/12/17 09:00}, Month = {Nov}, Number = {5903}, Own = {NLM}, Pages = {896--900}, Pii = {322/5903/896}, Pl = {United States}, pmid = {18988841}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review}, Rf = {44}, Sb = {IM}, Status = {MEDLINE}, Title = {Genes and social behavior}, Volume = {322}, Year = {2008}, url = {papers/Robinson_Science2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1159277}} @article{Pol:2006, Abstract = {A number of different RNA and DNA viruses can invade the brain and cause neurological dysfunction. These range from the tiny polio picornavirus, which has only 7kb of RNA genetic code that preferentially infects motor neurons, to the relatively large cytomegalovirus, which has >100 genes in its 235kb DNA genome and causes various neurological problems in the developing brain but is comparatively harmless to adults. This brief overview of some aspects of neurovirology addresses the complex problems that underlie an appreciation of the contribution of viral infections to brain disease. [This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).]}, Address = {Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA. anthony.vandenpol@yale.edu}, Author = {van den Pol, Anthony N}, Crdt = {2006/06/30 09:00}, Da = {20060731}, Date = {2006 Jul}, Date-Added = {2009-04-02 12:30:11 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20061010}, Dep = {20060627}, Edat = {2006/06/30 09:00}, Issn = {0166-2236 (Print)}, Jid = {7808616}, Journal = {Trends Neurosci}, Jt = {Trends in neurosciences}, Keywords = {21 Neurodegenerative}, Language = {eng}, Mh = {Animals; Brain Diseases/embryology/pathology/*virology; Central Nervous System Viral Diseases/*complications/pathology/physiopathology; Humans; Models, Biological; Neurons/ultrastructure/virology; Viruses/classification/*pathogenicity}, Mhda = {2006/10/13 09:00}, Month = {Jul}, Number = {7}, Own = {NLM}, Pages = {398--406}, Phst = {2006/02/09 {$[$}received{$]$}; 2006/05/09 {$[$}revised{$]$}; 2006/06/02 {$[$}accepted{$]$}; 2006/06/27 {$[$}aheadofprint{$]$}}, Pii = {S0166-2236(06)00113-5}, Pl = {England}, pmid = {16806513}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {65}, Sb = {IM}, Status = {MEDLINE}, Title = {Viral infections in the developing and mature brain}, Volume = {29}, Year = {2006}, url = {papers/Pol_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.06.002}} @article{Berkovic:2006, Abstract = {Epilepsies, once regarded as due to demoniacal possession, can have both genetic and acquired causes, with interaction of these factors in many cases. To date, nearly all the genes discovered to be involved in human epilepsies encode subunits of ion channels, both voltage-gated and ligand-gated. Established acquired causes include serious brain trauma, stroke, tumours and infective lesions. Thus, in terms of exploring the neurobiology of "nature and nurture" in disease, the epilepsies are an excellent paradigm. Here, we review the evidence and discuss the possibility that ion channels are a common biological substrate for both genetic and acquired epilepsies. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).}, Address = {Department of Medicine and Epilepsy Research, University of Melbourne, Austin Health, Heidelberg West, Victoria 3081, Australia. s.berkovic@unimelb.edu.au}, Author = {Berkovic, Samuel F and Mulley, John C and Scheffer, Ingrid E and Petrou, Steven}, Crdt = {2006/06/14 09:00}, Da = {20060907}, Date = {2006 Jul}, Date-Added = {2009-04-02 12:30:11 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20061010}, Edat = {2006/06/14 09:00}, Issn = {0166-2236 (Print)}, Jid = {7808616}, Journal = {Trends Neurosci}, Jt = {Trends in neurosciences}, Keywords = {21 Epilepsy}, Language = {eng}, Lr = {20071115}, Mh = {Anoxia/complications/genetics; Brain Neoplasms/complications/genetics; Environment; Epilepsy/*etiology/*genetics/physiopathology; Humans; Ion Channels/genetics/metabolism; Stroke/complications/genetics}, Mhda = {2006/10/13 09:00}, Month = {Jul}, Number = {7}, Own = {NLM}, Pages = {391--397}, Phst = {2006/02/08 {$[$}received{$]$}; 2006/05/03 {$[$}revised{$]$}; 2006/05/26 {$[$}accepted{$]$}}, Pii = {S0166-2236(06)00110-X}, Pl = {England}, pmid = {16769131}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {47}, Rn = {0 (Ion Channels)}, Sb = {IM}, Status = {MEDLINE}, Title = {Human epilepsies: interaction of genetic and acquired factors}, Volume = {29}, Year = {2006}, url = {papers/Berkovic_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.05.009}} @article{Persico:2006, Abstract = {Our understanding of human disorders that affect higher cognitive functions has greatly advanced in recent decades, and over 20 genes associated with non-syndromic mental retardation have been identified during the past 15 years. However, proteins encoded by "cognition genes" have such diverse neurodevelopmental functions that delineating specific pathogenetic pathways still poses a tremendous challenge. In this review, we summarize genetic, epigenetic and environmental contributions to neurodevelopmental alterations that either cause or confer vulnerability to autism, a disease primarily affecting social cognition. Taken together, these results begin to provide a unifying view of complex pathogenetic pathways that are likely to lead to autism spectrum disorders through altered neurite morphology, synaptogenesis and cell migration. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).}, Address = {Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Via Longoni 83, I-00155, Rome, Italy. a.persico@unicampus.it}, Author = {Persico, Antonio M and Bourgeron, Thomas}, Crdt = {2006/07/01 09:00}, Da = {20060731}, Date = {2006 Jul}, Date-Added = {2009-04-02 12:30:11 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20061010}, Dep = {20060630}, Edat = {2006/07/01 09:00}, Issn = {0166-2236 (Print)}, Jid = {7808616}, Journal = {Trends Neurosci}, Jt = {Trends in neurosciences}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Autistic Disorder/etiology/*genetics/pathology; Cell Movement/physiology; Disease Models, Animal; *Environment; Genetics, Behavioral; Humans; Linkage (Genetics); Nerve Tissue Proteins/*genetics/metabolism}, Mhda = {2006/10/13 09:00}, Month = {Jul}, Number = {7}, Own = {NLM}, Pages = {349--358}, Phst = {2006/01/18 {$[$}received{$]$}; 2006/04/18 {$[$}revised{$]$}; 2006/05/26 {$[$}accepted{$]$}; 2006/06/30 {$[$}aheadofprint{$]$}}, Pii = {S0166-2236(06)00111-1}, Pl = {England}, pmid = {16808981}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Review}, Rf = {133}, Rn = {0 (Nerve Tissue Proteins)}, Sb = {IM}, Status = {MEDLINE}, Title = {Searching for ways out of the autism maze: genetic, epigenetic and environmental clues}, Volume = {29}, Year = {2006}, url = {papers/Persico_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.05.010}} @article{Huberman:2003, Abstract = {The segregation of initially intermingled left and right eye inputs to the dorsal lateral geniculate nucleus (DLGN) during development is thought to be in response to precise spatial and temporal patterns of spontaneous ganglion cell activity. To test this hypothesis, we disrupted the correlated activity of neighboring ganglion cells in the developing ferret retina through immunotoxin depletion of starburst amacrine cells. Despite the absence of this type of correlated activity, left and right eye inputs segregated normally in the DLGN. By contrast, when all spontaneous activity was blocked, the projections from the two eyes remained intermingled. Thus, certain features of normal neural activity patterns are not required for the formation of eye-specific projections to the DLGN.}, Address = {Center for Neuroscience, School of Medicine, University of California, Davis, CA 95616, USA.}, Author = {Huberman, Andrew D and Wang, Guo-Yong and Liets, Lauren C and Collins, Odell A and Chapman, Barbara and Chalupa, Leo M}, Crdt = {2003/05/10 05:00}, Da = {20030509}, Date = {2003 May 9}, Date-Added = {2009-04-01 18:56:46 -0400}, Date-Modified = {2013-08-28 14:40:45 +0000}, Dcom = {20030616}, Edat = {2003/05/10 05:00}, Ein = {Science. 2003 Jun 13;300(5626):1661}, Gr = {EY03991/EY/NEI NIH HHS/United States; EY11369/EY/NEI NIH HHS/United States; EY12576/EY/NEI NIH HHS/United States; EY13301/EY/NEI NIH HHS/United States; P20 MH6095/MH/NIMH NIH HHS/United States; R01 EY011369-11/EY/NEI NIH HHS/United States}, Issn = {1095-9203 (Electronic)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {Non-programmatic; 21 Activity-development; 21 Neurophysiology; retinal wave paper; currOpinRvw}, Language = {eng}, Lr = {20090227}, Mh = {Action Potentials; Amacrine Cells/physiology; Animals; Axons/physiology; Calcium; Calcium Signaling; Carrier Proteins/immunology; Ferrets; Geniculate Bodies/growth \& development/*physiology; Immunotoxins/pharmacology; *Membrane Transport Proteins; N-Glycosyl Hydrolases; Patch-Clamp Techniques; Plant Proteins; Retina/growth \& development/*physiology; Retinal Ganglion Cells/*physiology; Ribosome Inactivating Proteins, Type 1; Vesicular Acetylcholine Transport Proteins; *Vesicular Transport Proteins; Visual Pathways/growth \& development/*physiology}, Mhda = {2003/06/17 05:00}, Mid = {NIHMS83820}, Month = {May}, Number = {5621}, Oid = {NLM: NIHMS83820; NLM: PMC2647844}, Oto = {NASA}, Own = {NLM}, Pages = {994--998}, Pii = {300/5621/994}, Pl = {United States}, Pmc = {PMC2647844}, pmid = {12738869}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Carrier Proteins); 0 (Immunotoxins); 0 (Membrane Transport Proteins); 0 (Plant Proteins); 0 (Ribosome Inactivating Proteins, Type 1); 0 (Vesicular Acetylcholine Transport Proteins); 0 (Vesicular Transport Proteins); 7440-70-2 (Calcium); EC 3.2.2.- (N-Glycosyl Hydrolases); EC 3.2.2.22 (saporin)}, Sb = {IM; S}, Status = {MEDLINE}, Title = {Eye-specific retinogeniculate segregation independent of normal neuronal activity}, Volume = {300}, Year = {2003}, url = {papers/Huberman_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1080694}} @article{Sun:2008, Abstract = {Epibatidine (EPI), a potent cholinergic agonist, disrupts acetylcholine-dependent spontaneous retinal activity. Early patch-clamp recordings in juvenile ferrets suggested that EPI blocks all retinal ganglion cell (RGC) action potentials when applied to the retina. In contrast, recent experiments on the developing mouse that relied on multielectrode array (MEA) recordings reported that EPI application decorrelates the activity of neighboring RGCs and eliminates retinal waves while preserving the spiking activity of many neurons. The different techniques used in previous studies raise the question of whether EPI has different effects on RGC activity in mouse compared with that in ferret. A resolution of this issue is essential for interpreting the results of developmental studies that relied on EPI to manipulate retinal activity. Our goal was to compare the effects of EPI on the spontaneous discharges of RGCs in mouse and ferret using 60-electrode MEA as well as patch-clamp recordings during the developmental stage when retinal waves are driven by acetylcholine in both species. We found that in both mouse and ferret EPI decorrelates RGC activity and eliminates retinal waves. However, EPI does not block all spontaneous activity in either species. Instead, our whole cell recordings reveal that EPI silences more than half of all RGCs while significantly increasing the activity of the remainder. These results have important implications for interpreting the results of previous studies that relied on this cholinergic agonist to perturb retinal activity.}, Address = {Department of Neurobiology, Physiology, and Behavior, School of Medicine, University of California, Davis, CA 95616, USA.}, Author = {Sun, Chao and Speer, Colenso M and Wang, Guo-Yong and Chapman, Barbara and Chalupa, Leo M}, Crdt = {2008/10/17 09:00}, Da = {20081208}, Date = {2008 Dec}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2012-07-06 13:39:29 +0000}, Dep = {20081015}, Edat = {2008/10/17 09:00}, Gr = {EY-03991/EY/NEI NIH HHS/United States; EY-11369/EY/NEI NIH HHS/United States; EY-13301/EY/NEI NIH HHS/United States; P20MH-60973/MH/NIMH NIH HHS/United States; R01 EY011369-11/EY/NEI NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Neurophysiology; 21 Activity-development; Ferrets; Mouse; Spontaneous activity; retinal wave paper; Neurophysiology; retina; Retinal Ganglion Cells/drug effects/physiology}, Language = {eng}, Mhda = {2008/10/17 09:00}, Month = {Dec}, Number = {6}, Oid = {NLM: PMC2604840 {$[$}Available on 12/01/09{$]$}}, Own = {NLM}, Pages = {3253--3263}, Phst = {2008/10/15 {$[$}aheadofprint{$]$}}, Pii = {90303.2008}, Pl = {United States}, Pmc = {PMC2604840}, Pmcr = {2009/12/01}, pmid = {18922954}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Sb = {IM}, Source = {J Neurophysiol. 2008 Dec;100(6):3253-63. Epub 2008 Oct 15.}, Status = {In-Process}, Title = {Epibatidine application in vitro blocks retinal waves without silencing all retinal ganglion cell action potentials in developing retina of the mouse and ferret}, Volume = {100}, Year = {2008}, url = {papers/Sun_JNeurophysiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.90303.2008}} @article{Sun:2008a, Abstract = {The structural and functional properties of the visual system are disrupted in mutant animals lacking the beta2 subunit of the nicotinic acetylcholine receptor. In particular, eye-specific retinogeniculate projections do not develop normally in these mutants. It is widely thought that the developing retinas of beta2(-/-) mutants do not manifest correlated activity, leading to the notion that retinal waves play an instructional role in the formation of eye-specific retinogeniculate projections. By multielectrode array recordings, we show here that the beta2(-/-) mutants have robust retinal waves during the formation of eye-specific projections. Unlike in WT animals, however, the mutant retinal waves are propagated by gap junctions rather than cholinergic circuitry. These results indicate that lack of retinal waves cannot account for the abnormalities that have been documented in the retinogeniculate pathway of the beta2(-/-) mutants and suggest that other factors must contribute to the deficits in the visual system that have been noted in these animals.}, Address = {Departments of Neurobiology, Physiology, and Behavior, and Ophthalmology and Vision Science, University of California, Davis, CA 95616, USA.}, Author = {Sun, Chao and Warland, David K and Ballesteros, Jose M and van der List, Deborah and Chalupa, Leo M}, Crdt = {2008/09/02 09:00}, Da = {20080910}, Date = {2008 Sep 9}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2013-08-27 20:06:53 +0000}, Dcom = {20080930}, Dep = {20080829}, Edat = {2008/09/02 09:00}, Gr = {EY003991/EY/NEI NIH HHS/United States; EY016182/EY/NEI NIH HHS/United States; P30 EY12576/EY/NEI NIH HHS/United States}, Issn = {1091-6490 (Electronic)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Neurophysiology; 21 Activity-development; currOpinRvw; retinal waves; spontaneous activity; visual system; mice; mouse; Acetylcholine}, Language = {eng}, Lr = {20081120}, Mh = {Animals; Mice; Mice, Knockout; Mutation/genetics; Receptors, Nicotinic/*deficiency/genetics; Retina/metabolism/*physiology}, Mhda = {2008/10/01 09:00}, Month = {Sep}, Number = {36}, Oid = {NLM: PMC2527347}, Own = {NLM}, Pages = {13638--13643}, Phst = {2008/08/29 {$[$}aheadofprint{$]$}}, Pii = {0807178105}, Pl = {United States}, Pmc = {PMC2527347}, pmid = {18757739}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Chrnb2 protein, mouse); 0 (Receptors, Nicotinic)}, Sb = {IM}, Source = {Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13638-43. Epub 2008 Aug 29.}, Status = {MEDLINE}, Title = {Retinal waves in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor}, Volume = {105}, Year = {2008}, url = {papers/Sun_ProcNatlAcadSciUSA2008.pdf}, Bdsk-File-2 = {papers/Sun_ProcNatlAcadSciUSA2008a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0807178105}} @article{Chalupa:2007, Abstract = {In all mammalian species the projections from the two eyes to the dorsal lateral geniculate nucleus of the thalamus terminate in separate layers or territories. This mature projection pattern is refined early in development from an initial state where the inputs of the two eyes are overlapping. Here I discuss the results of studies showing that the formation of segregated eye-specific retinogeniculate projections involves activity-mediated binocular competition. I conclude that while retinal activity undoubtedly is involved in this process, the results of recent studies cast doubt on the prevalent notion that retinal waves of activity play an instructional role in the formation of segregated retinal projections.}, Address = {Department of Ophthalmology and Vision Science, School of Medicine and Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, CA 95616, USA. lmchalupa@ucdavis.edu}, Author = {Chalupa, Leo M}, Crdt = {2007/04/17 09:00}, Da = {20071015}, Date = {2007 Oct}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080206}, Dep = {20070313}, Edat = {2007/04/17 09:00}, Gr = {EY 016182/EY/NEI NIH HHS/United States; EY 03391/EY/NEI NIH HHS/United States; P20 MH 6095/MH/NIMH NIH HHS/United States}, Issn = {0165-0173 (Print)}, Jid = {101300366}, Journal = {Brain Res Rev}, Jt = {Brain research reviews}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal wave paper}, Language = {eng}, Mh = {Animals; Geniculate Bodies/growth \& development/*physiology; Retina/growth \& development/*physiology; Visual Pathways/growth \& development/*physiology}, Mhda = {2008/02/07 09:00}, Month = {Oct}, Number = {2}, Own = {NLM}, Pages = {228--236}, Phst = {2006/12/12 {$[$}received{$]$}; 2007/03/07 {$[$}revised{$]$}; 2007/03/07 {$[$}accepted{$]$}; 2007/03/13 {$[$}aheadofprint{$]$}}, Pii = {S0165-0173(07)00039-2}, Pl = {Netherlands}, pmid = {17433447}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review}, Rf = {46}, Sb = {IM}, Source = {Brain Res Rev. 2007 Oct;55(2):228-36. Epub 2007 Mar 13.}, Status = {MEDLINE}, Title = {A reassessment of the role of activity in the formation of eye-specific retinogeniculate projections}, Volume = {55}, Year = {2007}, url = {papers/Chalupa_BrainResRev2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainresrev.2007.03.003}} @article{Stellwagen:2002, Abstract = {A central hypothesis of neural development is that patterned activity drives the refinement of initially imprecise connections. We have examined this hypothesis directly by altering the frequency of spontaneous waves of activity that sweep across the mammalian retina prior to vision. Activity levels were increased in vivo using agents that elevate cAMP. When one eye is made more active, its layer within the LGN is larger despite the other eye having normal levels of activity. Remarkably, when the frequency of retinal waves is increased in both eyes, normally sized layers form. Because relative, rather than absolute, levels of activity between the eyes regulate the amount of LGN territory devoted to each eye, we conclude that activity acts instructively to guide binocular segregation during development.}, Address = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Author = {Stellwagen, D and Shatz, C J}, Crdt = {2002/02/08 10:00}, Da = {20020208}, Date = {2002 Jan 31}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2013-07-16 15:27:27 +0000}, Dcom = {20020305}, Edat = {2002/02/08 10:00}, Gr = {GM0748/GM/NIGMS NIH HHS/United States; MH48108/MH/NIMH NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development; epibatidine; Spontaneous activity; retinal wave paper; Ferrets; LGN; retina; visual system; structural remodeling; Structure-Activity Relationship; currOpinRvw}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Animals, Newborn; Bicyclo Compounds, Heterocyclic/pharmacology; Cholera Toxin/pharmacology; Cyclic AMP/analogs \& derivatives/*metabolism; Dendrites/ultrastructure; Ferrets; Fluorescent Dyes/administration \& dosage/metabolism; Forskolin/pharmacology; Functional Laterality; Geniculate Bodies/anatomy \& histology/*metabolism; Histocytochemistry; Nicotinic Agonists/pharmacology; Patch-Clamp Techniques; Pyridines/pharmacology; Retina/cytology/drug effects/growth \& development/*physiology; Retinal Ganglion Cells/cytology; Vision, Binocular/physiology; Visual Pathways/growth \& development/*physiology}, Mhda = {2002/03/07 10:01}, Month = {Jan}, Number = {3}, Own = {NLM}, Pages = {357-367}, Pii = {S0896627302005779}, Pl = {United States}, pmid = {11832224}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Bicyclo Compounds, Heterocyclic); 0 (Fluorescent Dyes); 0 (Nicotinic Agonists); 0 (Pyridines); 140111-52-0 (epibatidine); 60-92-4 (Cyclic AMP); 66428-89-5 (Forskolin); 9012-63-9 (Cholera Toxin)}, Sb = {IM}, Source = {Neuron. 2002 Jan 31;33(3):357-67.}, Status = {MEDLINE}, Title = {An instructive role for retinal waves in the development of retinogeniculate connectivity}, Volume = {33}, Year = {2002}, url = {papers/Stellwagen_Neuron2002.pdf}} @article{Cook:1999, Abstract = {During early mammalian development, inputs from the two retinas intermix within the lateral geniculate nucleus (LGN), then segregate during the first postnatal week into layers that receive input from a single retina. Functionally, the LGN also changes markedly during the first postnatal month; early geniculate responses to retinal input are mainly excitatory, then inhibitory circuits mature within the LGN. These remarkable changes in form and function of the retinogeniculate pathway occur at a time when patterned visual activity is not present, but retinal ganglion cells already manifest spontaneous action potential activity. To examine the role of early retinal activity in these critical developmental processes, we placed the slow release polymer Elvax embedded with tetrodotoxin (TTX) into the vitreous chamber of one or both eyes of neonatal ferrets. Animals receiving monocular injection of TTX had the other eye treated with Elvax containing control citrate buffer. Intraocular injection of horseradish peroxidase was made at the end of the period of TTX treatment to reveal the retinal terminals in the LGN. Chronic monocular or binocular blockade of retinal activity during the first postnatal week did not prevent eye-specific segregation, although it made the boundaries between layers less distinct. Retinal terminals ended preferentially in the appropriate layer, but a large number of terminals were also present in the inappropriate layer. Further segregation was achieved during the second postnatal week of activity blockade, when most retinal terminals ended preferentially in the appropriate geniculate layer and sharper layer boundaries were present. However, a small but significant number of terminals still extended into the inappropriate layer. Together, these findings indicate that monocular as well as binocular blockade of retinal activity resulted in some anomalous retinogeniculate projections and delayed eye-specific patterning, but segregation was largely intact at the end of the second postnatal week. We also report here that intraocular tetrodotoxin had a marked effect on the maturation of intrinsic geniculate circuits prior to eye opening. Whole-cell patch-clamp recordings in the LGN slice preparation revealed that activity blockade prevented the maturation of the slow, but not the fast, hyperpolarizing potential of LGN neurons during the first postnatal month and up to P38, the oldest age studied. In conclusion, these results indicate that spontaneous retinal activity modulates the time course of binocular segregation but does not alone account for the segregation of retinogeniculate terminals. However, early retinal activity plays an important role in developing the intrinsic circuitry of the LGN.}, Address = {Department of Anatomy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.}, Author = {Cook, P M and Prusky, G and Ramoa, A S}, Crdt = {1999/06/01 00:00}, Da = {19990803}, Date = {1999 May-Jun}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2011-09-23 10:14:52 -0400}, Dcom = {19990803}, Edat = {1999/06/01}, Gr = {EY 11508/EY/NEI NIH HHS/United States}, Issn = {0952-5238 (Print)}, Jid = {8809466}, Journal = {Vis Neurosci}, Jt = {Visual neuroscience}, Keywords = {mouse; function; Behavior; visual system; Retina; visual cortex; plasticity; acuity; Sensory Deprivation; 21 Activity-development; Binocular; Monocular; bilateral; sensory map; topographic map; 21 Neurophysiology; Spontaneous activity; Structure-Activity Relationship; structural remodeling; ferret; LGN}, Language = {eng}, Lr = {20071114}, Mh = {Action Potentials/drug effects/physiology; Animals; Ferrets; Geniculate Bodies/drug effects/growth \& development/*physiology; Patch-Clamp Techniques; Retina/drug effects/growth \& development/*physiology; Synaptic Transmission/drug effects/physiology; Tetrodotoxin/pharmacology; Visual Pathways/drug effects/growth \& development/*physiology}, Mhda = {1999/06/01 00:01}, Month = {May-Jun}, Number = {3}, Own = {NLM}, Pages = {491--501}, Pl = {ENGLAND}, pmid = {10349970}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Rn = {4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Source = {Vis Neurosci. 1999 May-Jun;16(3):491-501.}, Status = {MEDLINE}, Title = {The role of spontaneous retinal activity before eye opening in the maturation of form and function in the retinogeniculate pathway of the ferret}, Volume = {16}, Year = {1999}, url = {papers/Cook_VisNeurosci1999.pdf}} @article{Penn:1998, Abstract = {When contacts are first forming in the developing nervous system, many neurons generate spontaneous activity that has been hypothesized to shape appropriately patterned connections. In Mustela putorius furo, monocular intraocular blockade of spontaneous retinal waves of action potentials by cholinergic agents altered the subsequent eye-specific lamination pattern of the lateral geniculate nucleus (LGN). The projection from the active retina was greatly expanded into territory normally belonging to the other eye, and the projection from the inactive retina was substantially reduced. Thus, interocular competition driven by endogenous retinal activity determines the pattern of eye-specific connections from retina to LGN, demonstrating that spontaneous activity can produce highly stereotyped patterns of connections before the onset of visual experience.}, Address = {Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. apenn@uclink2.berkeley.edu}, Author = {Penn, A A and Riquelme, P A and Feller, M B and Shatz, C J}, Crdt = {1998/04/16 00:00}, Da = {19980408}, Date = {1998 Mar 27}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2013-08-27 20:45:31 +0000}, Dcom = {19980408}, Edat = {1998/04/16}, Gr = {MH 98108/MH/NIMH NIH HHS/United States}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal wave paper; Spontaneous activity; topographic map; Structure-Activity Relationship; visual system; LGN; retina; Retinal Ganglion Cells/drug effects/physiology; Ferrets; currOpinRvw}, Language = {eng}, Lr = {20071114}, Mh = {Action Potentials/drug effects; Animals; Animals, Newborn; Axons/physiology; Bicyclo Compounds, Heterocyclic/pharmacology; Bungarotoxins/pharmacology; *Conotoxins; Ferrets; Geniculate Bodies/*anatomy \& histology/growth \& development; Microspheres; Nicotinic Agonists/pharmacology; Peptides/pharmacology; Pyridines/pharmacology; Retina/drug effects/*physiology; Retinal Ganglion Cells/drug effects/*physiology; *Visual Pathways}, Mhda = {1998/04/16 00:01}, Month = {Mar}, Number = {5359}, Own = {NLM}, Pages = {2108-2112}, Pl = {UNITED STATES}, pmid = {9516112}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Bicyclo Compounds, Heterocyclic); 0 (Bungarotoxins); 0 (Conotoxins); 0 (Nicotinic Agonists); 0 (Peptides); 0 (Pyridines); 0 (alpha-conotoxin MII); 140111-52-0 (epibatidine)}, Sb = {IM}, Source = {Science. 1998 Mar 27;279(5359):2108-12.}, Status = {MEDLINE}, Title = {Competition in retinogeniculate patterning driven by spontaneous activity}, Volume = {279}, Year = {1998}, url = {papers/Penn_Science1998.pdf}} @article{Rhoades:1981, Author = {Rhoades, R W and DellaCroce, D D and Meadows, I}, Crdt = {1981/10/01 00:00}, Da = {19811222}, Date = {1981 Oct}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2009-04-01 18:17:09 -0400}, Dcom = {19811222}, Edat = {1981/10/01}, Gr = {EY03546/EY/NEI NIH HHS/United States; NS16001/NS/NINDS NIH HHS/United States; RR09085/RR/NCRR NIH HHS/United States; etc.}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Animals, Newborn/*anatomy \& histology/physiology; Cricetinae; Eye/*innervation; Nerve Degeneration; Neurons/physiology; Reaction Time; Somatosensory Cortex/*anatomy \& histology/physiology; Spinal Cord/anatomy \& histology/physiology; Superior Colliculi/*anatomy \& histology/physiology}, Mhda = {1981/10/01 00:01}, Month = {Oct}, Number = {4}, Own = {NLM}, Pages = {855--877}, Pl = {UNITED STATES}, pmid = {7288468}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {J Neurophysiol. 1981 Oct;46(4):855-77.}, Status = {MEDLINE}, Title = {Reorganization of somatosensory input to superior colliculus in neonatally enucleated hamsters: anatomical and electrophysiological experiments}, Volume = {46}, Year = {1981}, url = {papers/Rhoades_JNeurophysiol1981.pdf}} @article{Rhoades:1980, Abstract = {1. The responses of visual, auditory and somatosensory superior collicular neurones were investigated using extracellular single unit recording techniques in hamsters which were subjected to the removal of one eye on the day of birth. 2. Neonatal enucleation resulted in a marked increase in the region of the colliculus from which visual neurones activated by stimulation of the ipsilateral eye could be recorded. In most cases the visuotopic representation in the colliculus ipsilateral to the remaining eye mirrored that observed in the contralateral tectum along both the rostrocaudal and mediolateral axes: in both colliculi temporal retina projected rostrally and inferior retina medially. In some animals, however, there appeared to be a dual mapping of the remaining eye onto the ipsilateral tectum. In these hamsters the central portion of the visual field was represented twice along the rostrocaudal axis of colliculus. 3. No changes in the topography of the somatosensory and auditory representations in the tectum were observed following neonatal enucleation. 4. The laminar distribution of visual neurones in the ipsilateral colliculus was markedly altered in the neonatally enucleated hamsters. Very few exclusively visual units were encountered in the layers ventral to the stratum opticum and almost all of the visual cells recorded in the ipsilateral colliculus were isolated within 150 microM of the tectal surface. 5. In the posterior half of the ipsilateral tectum a large number of extravisually responsive cells were encountered in the stratum griseum superficiale and stratum opticum. This was not the case in the colliculus contralateral to the remaining eye, nor has it ever been observed in normal hamsters. 6. Recordings from animals subjected to both neonatal enucleation and acute bilateral removal of somatosensory and auditory cortex indicated that the projections from these areas to the colliculus were not essential to the observed changes in laminar organization. 7. Recordings from normally reared hamsters which were subjected to removal of one eye at the time of the recording experiment suggested further that the isolation of extravisual cells in the superficial tectal aminae of the neonatal enucleates was probably not the result of the 'unmasking' of extravisual influences in the superficial layers which are present, but ineffective, in the normal case.}, Author = {Rhoades, R W}, Crdt = {1980/04/01 00:00}, Da = {19801125}, Date = {1980 Apr}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2009-04-01 18:17:09 -0400}, Dcom = {19801125}, Edat = {1980/04/01}, Gr = {1 508 RR-09085/RR/NCRR NIH HHS/United States; 1 R03 MH 32897-01/MH/NIMH NIH HHS/United States}, Issn = {0022-3751 (Print)}, Jid = {0266262}, Journal = {J Physiol}, Jt = {The Journal of physiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {Action Potentials; Animals; Animals, Newborn/*physiology; Auditory Cortex/physiology; Cricetinae; Mesocricetus; Neurons/physiology; *Ocular Physiological Phenomena; Somatosensory Cortex/physiology; Superior Colliculi/anatomy \& histology/*physiology; Visual Cortex/physiology}, Mhda = {1980/04/01 00:01}, Month = {Apr}, Oid = {NLM: PMC1279405}, Own = {NLM}, Pages = {383--399}, Pl = {ENGLAND}, Pmc = {PMC1279405}, pmid = {7411438}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {J Physiol. 1980 Apr;301:383-99.}, Status = {MEDLINE}, Title = {Effects of neonatal enucleation on the functional organization of the superior colliculus in the golden hamster}, Volume = {301}, Year = {1980}, url = {papers/Rhoades_JPhysiol1980.pdf}} @article{Hoffmann:1974, Author = {Hoffmann, K P and Sherman, S M}, Crdt = {1974/11/01 00:00}, Da = {19750310}, Date = {1974 Nov}, Date-Added = {2009-04-01 18:08:58 -0400}, Date-Modified = {2009-04-01 18:17:09 -0400}, Dcom = {19750310}, Edat = {1974/11/01}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {Age Factors; Animals; Brain Mapping; Cats; Dominance, Cerebral; Electric Stimulation; Electrophysiology; Motion Perception; Neural Conduction; Neurons/physiology; *Sensory Deprivation; Superior Colliculi/*physiology; Time Factors; *Vision, Ocular; Visual Fields; Visual Pathways/*physiology; *Visual Perception}, Mhda = {1974/11/01 00:01}, Month = {Nov}, Number = {6}, Own = {NLM}, Pages = {1276--1286}, Pl = {UNITED STATES}, pmid = {4436700}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Status = {MEDLINE}, Title = {Effects of early monocular deprivation on visual input to cat superior colliculus}, Volume = {37}, Year = {1974}, url = {papers/Hoffmann_JNeurophysiol1974.pdf}} @article{Sakata:2006, Abstract = {Although the N-methyl-D-aspartate (NMDA) receptor is known to play a crucial role in activity-dependent remodeling of synaptic connections in the fetal superior colliculus (SC), its contribution to the electrical activity of fetal SC neurons has not been determined. Furthermore, whether gamma-aminobutyric acid (GABA)-mediated inhibition occurs either as early as prenatal periods or only after eye opening has been controversial. We therefore performed optical recordings using voltage-, Ca2+- and Cl--sensitive fluorescent dyes to analyse synaptic transmission and changes in intracellular Ca2+ and Cl- in the SC of fetal rats that were still connected with the dams by the umbilical cord. Excitatory and inhibitory responses were evoked by focal SC stimulation. The excitatory synaptic responses are composed of early and late components. The early component was mediated by both non-NMDA and NMDA receptors, whereas the late component occurred mainly via NMDA receptors. Train pulse stimulation at higher currents was required for induction of the inhibition, which was antagonized by bicuculline, and blocking of the GABA-mediated inhibition by bicuculline uncovered masked excitatory synaptic responses. Focal SC stimulation induced increases in [Cl-]i and [Ca2+]i that were mediated by GABA-A receptors and mainly by NMDA receptors, respectively. GABA antagonists augmented SC-induced increases in [Ca2+]i. These results indicate that, in the fetal SC, excitatory and inhibitory synaptic transmissions occur before birth, that the NMDA receptor is a major contributor to excitatory synaptic transmission and increased [Ca2+]i, and that the GABA-A receptor is already functioning to inhibit excitatory neurotransmission.}, Address = {Department of Neuroscience, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.}, Author = {Sakata, Yoshiyuki and Fujioka, Takashi and Endoh, Hisashi and Nakamura, Shoji}, Crdt = {2006/03/24 09:00}, Da = {20060323}, Date = {2006 Mar}, Date-Added = {2009-03-30 11:13:41 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060530}, Edat = {2006/03/24 09:00}, Issn = {0953-816X (Print)}, Jid = {8918110}, Journal = {Eur J Neurosci}, Jt = {The European journal of neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {2-Amino-5-phosphonovalerate/pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology; Animals; Axons/physiology; Calcium/*metabolism; Chlorides/*metabolism; Dose-Response Relationship, Drug; Electric Stimulation; Electrophysiology; Excitatory Amino Acid Antagonists/pharmacology; Female; Fluorescent Dyes; Pregnancy; Rats; Rats, Sprague-Dawley; Receptors, GABA/physiology; Receptors, Glutamate/physiology; Receptors, N-Methyl-D-Aspartate/physiology; Superior Colliculi/cytology/*metabolism; Synaptic Transmission/*physiology; Tetrodotoxin/pharmacology}, Mhda = {2006/05/31 09:00}, Month = {Mar}, Number = {6}, Own = {NLM}, Pages = {1405--1416}, Pii = {EJN4683}, Pl = {France}, pmid = {16553604}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Chlorides); 0 (Excitatory Amino Acid Antagonists); 0 (Fluorescent Dyes); 0 (Receptors, GABA); 0 (Receptors, Glutamate); 0 (Receptors, N-Methyl-D-Aspartate); 115066-14-3 (6-Cyano-7-nitroquinoxaline-2,3-dione); 4368-28-9 (Tetrodotoxin); 7440-70-2 (Calcium); 76726-92-6 (2-Amino-5-phosphonovalerate)}, Sb = {IM}, Status = {MEDLINE}, Title = {In vivo optical recordings of synaptic transmission and intracellular Ca2+ and Cl- in the superior colliculus of fetal rats}, Volume = {23}, Year = {2006}, url = {papers/Sakata_EurJNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.04683.x}} @article{ODonovan:1999, Abstract = {Spontaneous neuronal activity has been detected in many parts of the developing vertebrate nervous system. Recent studies suggest that this activity depends on properties that are probably shared by all developing networks. Of particular importance is the high excitability of recurrently connected, developing networks and the presence of activity-induced transient depression of network excitability. In the spinal cord, it has been proposed that the interaction of these properties gives rise to spontaneous, periodic activity.}, Address = {Laboratory of Neural Control The National Institute of Neurological Disorders and Stroke National Institutes of Health Bethesda Maryland 20892 USA. odonovan@codon.nih.gov}, Author = {O'Donovan, M J}, Crdt = {1999/03/11 00:00}, Da = {19990524}, Date = {1999 Feb}, Date-Added = {2009-03-30 11:04:17 -0400}, Date-Modified = {2009-03-30 11:04:38 -0400}, Dcom = {19990524}, Edat = {1999/03/11}, Issn = {0959-4388 (Print)}, Jid = {9111376}, Journal = {Curr Opin Neurobiol}, Jt = {Current opinion in neurobiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20041117}, Mh = {Animals; Central Nervous System/*embryology; Chick Embryo; Cholinergic Antagonists/pharmacology; Drosophila; Excitatory Amino Acids/pharmacology; Nerve Net/drug effects/*embryology/physiology; Patch-Clamp Techniques; Rabbits; Rats; Retina/embryology; Synaptic Transmission/drug effects/*physiology; Turtles; gamma-Aminobutyric Acid/pharmacology}, Mhda = {1999/03/11 00:01}, Month = {Feb}, Number = {1}, Own = {NLM}, Pages = {94--104}, Pii = {S0959-4388(99)80012-9}, Pl = {ENGLAND}, pmid = {10072366}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {75}, Rn = {0 (Cholinergic Antagonists); 0 (Excitatory Amino Acids); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {The origin of spontaneous activity in developing networks of the vertebrate nervous system}, Volume = {9}, Year = {1999}, url = {papers/O'Donovan_CurrOpinNeurobiol1999.pdf}} @article{Reece:1998, Abstract = {This article describes the onset of electrical excitability and synaptic transmission in the retinocollicular pathway of the fetal and early postnatal rat, utilizing a novel in vitro preparation. Although the optic nerve is visible in embryonic day (E) 14 brain, its stimulation produced no response in the superior colliculus (SC) until E16 when a low voltage simple negative wave was evoked. At E17 these potentials were blocked rapidly, completely, and reversibly when choline was substituted for sodium or with the addition of cobalt ions. In the course of establishing the block with either of the above agents the latency of response increased, indicating an action on axonal transmission. By E20 the collicular evoked potential showed a short followed by a longer latency wave. The latter was blocked by the glutamate antagonist kynurenic acid, with latency unaffected. Further examination of potentials with the addition of glutamatergic receptor subtype blockers aminophosphonopentanoic acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione/6,7-dinitroquinoxaline- 2,3-dione (CNQX/DNQX) showed a clear abolition of the elicited potentials by E20 and older. Thus, fetal rat optic nerve fibers are capable of conduction in response to electrical stimulation as soon as they reach the SC at E16. Both sodium and calcium are involved. GABA-mediated modulation of axonal conduction is evident by E18. Glutaminergic synaptic transmission is established by E20. The timetable of fetal onset of capability to conduct and support synaptic transmission in the retinocollicular pathway is earlier than had previously been reported in vivo in the rat in which the superior colliculus neurones are said not to be driven by the optic nerve until 6 days post natal. This has relevance to the possible role of impulse activity in development of the pathway.}, Address = {Developmental Neurobiology Group, Research School of Biological Sciences, Australian National University, Canberra, Australia. laura.reece@anu.edu.au}, Author = {Reece, L J and Lim, C H}, Crdt = {1998/04/29 00:00}, Da = {19980618}, Date = {1998 Mar 12}, Date-Added = {2009-03-30 10:18:02 -0400}, Date-Modified = {2009-03-30 10:18:24 -0400}, Dcom = {19980618}, Edat = {1998/04/29}, Issn = {0165-3806 (Print)}, Jid = {8908639}, Journal = {Brain Res Dev Brain Res}, Jt = {Brain research. Developmental brain research}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Animals, Newborn; Electric Stimulation; Embryonic and Fetal Development/physiology; Evoked Potentials, Visual/*physiology; Gestational Age; *Neural Conduction; Optic Nerve/embryology/growth \& development/*physiology; Rats; Rats, Wistar; Superior Colliculi/embryology/growth \& development/*physiology; Synaptic Transmission/*physiology}, Mhda = {1998/04/29 00:01}, Month = {Mar}, Number = {1-2}, Own = {NLM}, Pages = {25--38}, Pl = {NETHERLANDS}, pmid = {9554940}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {Brain Res Dev Brain Res. 1998 Mar 12;106(1-2):25-38.}, Status = {MEDLINE}, Title = {Onset of optic nerve conduction and synaptic potentials in superior colliculus of fetal rats studied in vitro}, Volume = {106}, Year = {1998}, url = {papers/Reece_BrainResDevBrainRes1998.pdf}} @article{Itaya:1995, Abstract = {During the first 10 days after birth in the rat there are a succession of major developmental stages in the retinotectal pathway. During most of this time, the only recordable event in the superior colliculus is spontaneous activity. We studied and characterized this spontaneous activity, hypothesizing that it could play an important role in pathway development. The spontaneous discharges are detectable on postnatal day 5 (P5). After P5, the number of spontaneously active cells per penetration increases up to P10, after which they decrease to adult-like levels by P14-P15. Between P5 and P10, the spontaneous discharges exhibit several patterns of activity, from constant firing to intermittent bursts with periods of quiescence, without any bearing to age. We isolated the retina and superior colliculus by injecting xylocaine onto the optic nerve and found no change in collicular activity. While this suggests that the spontaneous activity in the colliculus is independent of the retina at the ages studied, the opposite experiment, i.e., electrically stimulating the optic nerve, resulted in increased firing by collicular neurons, perhaps via nonclassical synaptic transmission. Finally, we compared interval histograms for spontaneously active cells between P5 and P15. The histograms suggest that at certain ages, spontaneous firing is more regular; moreover, these ages precede major functional advances, e.g., onset of numerous spontaneously firing cells at P6, the first response to optic nerve stimulation at P10, and the first light-evoked response at P12-P13. Our results support the hypothesis that spontaneous activity in the neonatal superior colliculus has a role in development of the retinotectal pathway, but the data also indicate that classical synaptic transmission is not involved.}, Address = {Department of Biomedical Sciences, University of South Alabama, Mobile 36688, USA.}, Author = {Itaya, S K and Fortin, S and Molotchnikoff, S}, Crdt = {1995/09/01 00:00}, Da = {19961024}, Date = {1995 Sep}, Date-Added = {2009-03-30 10:18:02 -0400}, Date-Modified = {2009-03-30 10:18:24 -0400}, Dcom = {19961024}, Edat = {1995/09/01}, Issn = {0008-4212 (Print)}, Jid = {0372712}, Journal = {Can J Physiol Pharmacol}, Jt = {Canadian journal of physiology and pharmacology}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Animals, Suckling; Optic Nerve/*physiology; Rats; Superior Colliculi/*growth \& development/*physiology; Visual Pathways/*growth \& development}, Mhda = {1995/09/01 00:01}, Month = {Sep}, Number = {9}, Own = {NLM}, Pages = {1372--1377}, Pl = {CANADA}, pmid = {8748987}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Source = {Can J Physiol Pharmacol. 1995 Sep;73(9):1372-7.}, Status = {MEDLINE}, Title = {Evolution of spontaneous activity in the developing rat superior colliculus}, Volume = {73}, Year = {1995}} @article{Molotchnikoff:1993, Abstract = {Electrophysiological activity in the neonatal rat superior colliculus was recorded to measure neuronal and synaptic activity, and, therefore, functional development. Neonatal rat pups were studied from five days to two weeks of age. The earliest activity in the superior colliculus were spontaneous discharges at a frequency of one unit per animal on postnatal day 6 (P6). Spontaneously discharging units were more numerous at P8, and the number peaked on P10. The first clear response to optic nerve stimulation was seen on P10, with relatively long and variable latencies. By P14, electrically evoked responses had much shorter latencies. The results are in line with the first response to light flash in the superior colliculus at P12/13. The evidence suggests that functional development of the rat retinotectal pathway begins at the end of the first week after birth, and that much of the functional maturation occurs mainly during the second week after birth.}, Address = {Department de Sciences Biologiques, Universite de Montreal, Que., Canada.}, Author = {Molotchnikoff, S and Itaya, S K}, Crdt = {1993/04/16 00:00}, Da = {19930610}, Date = {1993 Apr 16}, Date-Added = {2009-03-30 10:18:02 -0400}, Date-Modified = {2009-03-30 10:18:24 -0400}, Dcom = {19930610}, Edat = {1993/04/16}, Issn = {0165-3806 (Print)}, Jid = {8908639}, Journal = {Brain Res Dev Brain Res}, Jt = {Brain research. Developmental brain research}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Animals, Newborn/*growth \& development/physiology; Electric Stimulation; Evoked Potentials; Photic Stimulation; Rats; Retina/*growth \& development/physiology; Superior Colliculi/*growth \& development/physiology; Visual Pathways/*growth \& development/physiology}, Mhda = {1993/04/16 00:01}, Month = {Apr}, Number = {2}, Own = {NLM}, Pages = {300--304}, Pl = {NETHERLANDS}, pmid = {8485851}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Functional development of the neonatal rat retinotectal pathway}, Volume = {72}, Year = {1993}, url = {papers/Molotchnikoff_BrainResDevBrainRes1993.pdf}} @article{Fischer:1998, Abstract = {Competition for postsynaptic targets during development is thought to be driven by differences in temporal patterns of neuronal activity. In the ferret visual system, retinal ganglion cells that are responsive either to the onset (On) or to the offset (Off) of light exhibit similar patterns of spontaneous bursting activity early in development but later develop different bursting rhythms during the period when their axonal arbors segregate to occupy spatially distinct regions in the dorsal lateral geniculate nucleus. Here, we demonstrate that GABAergic transmission plays an important, although not exclusive, role in regulating the bursting patterns of morphologically identified On and Off ganglion cells. During the first and second postnatal weeks, blocking GABAA receptors leads to a decrease in the bursting activity of all ganglion cells, suggesting that GABA potentiates activity at the early ages. Subsequently, during the period of On-Off segregation in the geniculate nucleus, GABA suppresses ganglion cell bursting activity. In particular, On ganglion cells show significantly higher bursting rates when GABAergic transmission is blocked, but the bursting rates of Off ganglion cells are not affected systematically. Thus, developmental differences in the bursting rates of On and Off ganglion cells emerge as GABA becomes inhibitory and as it consistently and more strongly inhibits On compared with Off ganglion cells. Because in many parts of the CNS GABAergic circuits appear early in development, our results also implicate a potentially important and possibly general role for local inhibitory interneurons in creating distinct temporal patterns of presynaptic activity that are specific to each developmental period.}, Address = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.}, Author = {Fischer, K F and Lukasiewicz, P D and Wong, R O}, Crdt = {1998/06/06 00:00}, Da = {19980601}, Date = {1998 May 15}, Date-Added = {2009-03-29 22:20:36 -0400}, Date-Modified = {2011-03-24 10:49:06 -0400}, Dcom = {19980601}, Edat = {1998/06/06}, Gr = {EY02687/EY/NEI NIH HHS/United States; EY08922/EY/NEI NIH HHS/United States; EY10699/EY/NEI NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology;retina;visual system;development;GABA;Interneurons;Circuit structure-function}, Language = {eng}, Lr = {20071114}, Mh = {Aging/*physiology; Animals; Animals, Newborn; Bicuculline/pharmacology; Electrophysiology; Female; Ferrets; GABA Antagonists/pharmacology; Glycine/pharmacology; Glycine Agents/pharmacology; Membrane Potentials/drug effects/physiology; Periodicity; Picrotoxin/pharmacology; Pregnancy; Pyridazines/pharmacology; Receptors, GABA-A/agonists/antagonists \& inhibitors; Retinal Ganglion Cells/chemistry/*drug effects/*physiology; Strychnine/pharmacology; gamma-Aminobutyric Acid/*pharmacology}, Mhda = {1998/06/06 00:01}, Month = {May}, Number = {10}, Own = {NLM}, Pages = {3767--3778}, Pl = {UNITED STATES}, pmid = {9570807}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (GABA Antagonists); 0 (Glycine Agents); 0 (Pyridazines); 0 (Receptors, GABA-A); 104104-50-9 (gabazine); 124-87-8 (Picrotoxin); 485-49-4 (Bicuculline); 56-12-2 (gamma-Aminobutyric Acid); 56-40-6 (Glycine); 57-24-9 (Strychnine)}, Sb = {IM}, Status = {MEDLINE}, Title = {Age-dependent and cell class-specific modulation of retinal ganglion cell bursting activity by GABA}, Volume = {18}, Year = {1998}, url = {papers/Fischer_JNeurosci1998.pdf}} @article{Wong:2000, Abstract = {Synchronized spontaneous rhythmic activity is a feature common to many parts of the developing nervous system. In the early visual system, before vision, developing circuits in the retina generate synchronized patterns of bursting activity that contain information useful for patterning connections between retinal ganglion cells and their central targets. However, how developing retinal circuits generate and regulate these spontaneous activity patterns is still incompletely understood. Here we show that in developing retinal circuits, the nature of excitatory neurotransmission driving correlated bursting activity in ganglion cells is not fixed but undergoes a developmental shift from cholinergic to glutamatergic transmission. In addition, we show that this shift occurs as presynaptic glutamatergic bipolar cells form functional connections onto the ganglion cells, implicating the role of bipolar cells in providing endogenous drive to bursting activity later in development. This transition coincides with the period when subsets of ganglion cells (On and Off cells) develop distinct activity patterns that are thought to underlie the refinement of their connectivity with their central targets. Here, our results suggest that the differences in activity patterns of On and Off ganglion cells may be conferred by differential synaptic drive from On and Off bipolar cells, respectively. Taken together, our results suggest that the regulation of patterned spontaneous activity by neurotransmitters undergoes systematic change as new cellular elements are added to developing circuits and also that these new elements can help specify distinct activity patterns appropriate for shaping connectivity patterns at later ages.}, Address = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.}, Author = {Wong, W T and Myhr, K L and Miller, E D and Wong, R O}, Crdt = {2000/01/11 00:00}, Da = {20000127}, Date = {2000 Jan 1}, Date-Added = {2009-03-29 22:17:05 -0400}, Date-Modified = {2009-03-29 22:20:12 -0400}, Dcom = {20000127}, Edat = {2000/01/11}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {2-Amino-5-phosphonovalerate/pharmacology; Action Potentials/drug effects/physiology; Animals; Bicuculline/pharmacology; Cholinergic Fibers/physiology; Excitatory Amino Acid Antagonists/pharmacology; Ferrets; GABA Antagonists/pharmacology; Glutamic Acid/*metabolism; Glycine/physiology; Glycine Agents/pharmacology; Interneurons/cytology/physiology; Periodicity; Quinoxalines/pharmacology; Retina/cytology/*growth \& development/*physiology; Retinal Ganglion Cells/cytology/physiology; Strychnine/pharmacology; Synaptic Transmission/drug effects/*physiology; Vision, Ocular/physiology; Visual Pathways; gamma-Aminobutyric Acid/physiology}, Mhda = {2000/01/11 00:01}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {351--360}, Pl = {UNITED STATES}, pmid = {10627612}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Excitatory Amino Acid Antagonists); 0 (GABA Antagonists); 0 (Glycine Agents); 0 (Quinoxalines); 118876-58-7 (2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline); 485-49-4 (Bicuculline); 56-12-2 (gamma-Aminobutyric Acid); 56-40-6 (Glycine); 56-86-0 (Glutamic Acid); 57-24-9 (Strychnine); 76726-92-6 (2-Amino-5-phosphonovalerate)}, Sb = {IM; S}, Status = {MEDLINE}, Title = {Developmental changes in the neurotransmitter regulation of correlated spontaneous retinal activity}, Volume = {20}, Year = {2000}, url = {papers/Wong_JNeurosci2000.pdf}} @article{Tao:2005, Abstract = {The receptive field (RF) of single visual neurons undergoes progressive refinement during development. It remains largely unknown how the excitatory and inhibitory inputs on single developing neurons are refined in a coordinated manner to allow the formation of functionally correct circuits. Using whole-cell voltage-clamp recording from Xenopus tectal neurons, we found that RFs determined by excitatory and inhibitory inputs in more mature tectal neurons are spatially matched, with each spot stimulus evoking balanced synaptic excitation and inhibition. This emerges during development through a gradual reduction in the RF size and a transition from disparate to matched topography of excitatory and inhibitory inputs to the tectal neurons. Altering normal spiking activity of tectal neurons by either blocking or elevating GABA(A) receptor activity significantly impeded the developmental reduction and topographic matching of RFs. Thus, appropriate inhibitory activity is essential for the coordinated refinement of excitatory and inhibitory connections.}, Address = {Division of Neurobiology, Department of Molecular and Cell Biology, University of California, CA 94720, USA.}, Author = {Tao, Huizhong W and Poo, Mu-ming}, Cin = {Neuron. 2005 Mar 24;45(6):825-8. PMID: 15797544}, Crdt = {2005/03/31 09:00}, Da = {20050330}, Date = {2005 Mar 24}, Date-Added = {2009-03-29 21:35:36 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20050519}, Edat = {2005/03/31 09:00}, Gr = {EY015019/EY/NEI NIH HHS/United States; EY36999/EY/NEI NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Action Potentials/drug effects/physiology; Afferent Pathways/drug effects/growth \& development/*physiology; Animals; Excitatory Postsynaptic Potentials/drug effects/*physiology; GABA Agonists/pharmacology; GABA Antagonists/pharmacology; Glutamic Acid/metabolism; Neural Inhibition/drug effects/*physiology; Neuronal Plasticity/physiology; Optic Nerve/physiology; Patch-Clamp Techniques; Receptors, GABA-A/drug effects/metabolism; Retinal Ganglion Cells/physiology; Superior Colliculi/drug effects/growth \& development/*physiology; Synaptic Transmission/drug effects/physiology; Visual Fields/drug effects/*physiology; Xenopus laevis; gamma-Aminobutyric Acid/metabolism}, Mhda = {2005/05/20 09:00}, Month = {Mar}, Number = {6}, Own = {NLM}, Pages = {829--836}, Phst = {2003/09/17 {$[$}received{$]$}; 2004/06/28 {$[$}revised{$]$}; 2005/01/27 {$[$}accepted{$]$}}, Pii = {S0896-6273(05)00115-7}, Pl = {United States}, pmid = {15797545}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (GABA Agonists); 0 (GABA Antagonists); 0 (Receptors, GABA-A); 56-12-2 (gamma-Aminobutyric Acid); 56-86-0 (Glutamic Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Activity-dependent matching of excitatory and inhibitory inputs during refinement of visual receptive fields}, Volume = {45}, Year = {2005}, url = {papers/Tao_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.01.046}} @article{Milner:1999, Abstract = {Patterned spontaneous electrical activity has been demonstrated in a number of developing neural circuits and has been proposed to play a role in refining connectivity once axons reach their targets. Using an isolated spinal cord preparation, we have found that chick lumbosacral motor axons exhibit highly regular bursts of activity from embryonic day 4 (E4) (stage 24-25), shortly after they exit the spinal cord and while still en route toward their target muscles. Similar bursts could be evoked by stimulating descending pathways at cervical or thoracic levels. Unlike older embryonic cord circuits, the major excitatory transmitter driving activity was not glutamate but acetylcholine, acting primarily though nicotinic non-alpha7 receptors. The circuit driving bursting was surprisingly robust and plastic, because bursting was only transiently blocked by cholinergic antagonists, and following recovery, was now driven by GABAergic inputs. Permanent blockade of spontaneous activity was only achieved by a combination of cholinergic antagonists and bicuculline, a GABAA antagonist. The early occurrence of patterned motor activity suggests that it could be playing a role in either peripheral pathfinding or spinal cord circuit formation and maturation. Finally, the characteristic differences in burst parameters already evident between different motoneuron pools at E4 would require that the combination of transcription factors responsible for specifying pool identity to have acted even earlier.}, Address = {Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.}, Author = {Milner, L D and Landmesser, L T}, Crdt = {1999/04/07 00:00}, Da = {19990427}, Date = {1999 Apr 15}, Date-Added = {2009-03-29 21:27:44 -0400}, Date-Modified = {2009-03-29 21:29:11 -0400}, Dcom = {19990427}, Edat = {1999/04/07}, Gr = {NS 19640/NS/NINDS NIH HHS/United States; T32 HD07104/HD/NICHD NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Acetylcholine/*physiology; Action Potentials/drug effects; Animals; Bicuculline/pharmacology; Chick Embryo; GABA Antagonists/pharmacology; Glutamic Acid/pharmacology; Motor Neurons/*physiology; Neuromuscular Junction/*physiology; Nipecotic Acids/pharmacology; *Proline/*analogs \& derivatives; Receptors, Nicotinic/physiology; Synaptic Transmission/drug effects; gamma-Aminobutyric Acid/*physiology}, Mhda = {1999/04/07 00:01}, Month = {Apr}, Number = {8}, Own = {NLM}, Pages = {3007--3022}, Pl = {UNITED STATES}, pmid = {10191318}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (GABA Antagonists); 0 (Nipecotic Acids); 0 (Receptors, Nicotinic); 147-85-3 (Proline); 485-49-4 (Bicuculline); 498-95-3 (nipecotic acid); 51-84-3 (Acetylcholine); 56-12-2 (gamma-Aminobutyric Acid); 56-86-0 (Glutamic Acid); 56879-46-0 (homoproline)}, Sb = {IM}, Status = {MEDLINE}, Title = {Cholinergic and GABAergic inputs drive patterned spontaneous motoneuron activity before target contact}, Volume = {19}, Year = {1999}, url = {papers/Milner_JNeurosci1999.pdf}} @article{Kanold:2006, Abstract = {Synaptic plasticity during critical periods of development requires intact inhibitory circuitry. We report that subplate neurons are needed both for maturation of inhibition and for the proper sign of ocular dominance (OD) plasticity. Removal of subplate neurons prevents the developmental upregulation of genes involved in mature, fast GABAergic transmission in cortical layer 4, including GABA receptor subunits and KCC2, and thus prevents the switch to a hyperpolarizing effect of GABA. To understand the implications of these changes, a realistic circuit model was formulated. Simulations predicted that without subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons representing the deprived (less active) eye, exactly what was then observed experimentally. Simulations also account for published results showing that OD plasticity requires mature inhibition. Thus, subplate neurons regulate molecular machinery required to establish an adult balance of excitation and inhibition in layer 4, and thereby influence the outcome of OD plasticity.}, Address = {Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.}, Author = {Kanold, Patrick O and Shatz, Carla J}, Cin = {Neuron. 2006 Sep 7;51(5):524-6. PMID: 16950151}, Crdt = {2006/09/05 09:00}, Da = {20060904}, Date = {2006 Sep 7}, Date-Added = {2009-03-29 20:52:10 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20061025}, Edat = {2006/09/05 09:00}, Gr = {F32 EY 1352/EY/NEI NIH HHS/United States; R01 EY 02858/EY/NEI NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {10 Development; 10 circuit formation; 21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Cats; Dominance, Ocular/*physiology; Female; Gene Expression Regulation, Developmental; In Situ Hybridization; Male; *Models, Neurological; Neural Inhibition/*physiology; Neuronal Plasticity/*physiology; Neurons/*cytology/physiology; Organ Culture Techniques; Polymerase Chain Reaction; RNA, Messenger/analysis; Receptors, GABA/metabolism; Symporters/metabolism; Synaptic Transmission/physiology; Visual Cortex/*embryology/physiology; gamma-Aminobutyric Acid/metabolism}, Mhda = {2006/10/26 09:00}, Month = {Sep}, Number = {5}, Own = {NLM}, Pages = {627--638}, Phst = {2006/01/17 {$[$}received{$]$}; 2006/05/11 {$[$}revised{$]$}; 2006/07/06 {$[$}accepted{$]$}}, Pii = {S0896-6273(06)00548-4}, Pl = {United States}, pmid = {16950160}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Rn = {0 (RNA, Messenger); 0 (Receptors, GABA); 0 (Symporters); 0 (potassium-chloride symporters); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Subplate neurons regulate maturation of cortical inhibition and outcome of ocular dominance plasticity}, Volume = {51}, Year = {2006}, url = {papers/Kanold_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.07.008}} @article{Ohshiro:2006, Abstract = {Previous work demonstrates an essential role of subplate neurons during ocular dominance (OD) column formation in the developing visual cortex. While inhibitory circuitry has also been shown to play an essential role in OD plasticity, the relationship between subplate neurons and the development of inhibitory circuits has been unclear. In this issue of Neuron, Kanold and Shatz provide evidence that maturation of inhibitory circuitry requires subplate neurons in the developing cortex.}, Address = {Department of Brain and Cognitive Sciences, University of Rochester, Rochester, NY 14627, USA.}, Author = {Ohshiro, Tomokazu and Weliky, Michael}, Con = {Neuron. 2006 Sep 7;51(5):627-38. PMID: 16950160}, Crdt = {2006/09/05 09:00}, Da = {20060904}, Date = {2006 Sep 7}, Date-Added = {2009-03-29 20:52:10 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20061025}, Edat = {2006/09/05 09:00}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {10 Development; 10 circuit formation; 21 Neurophysiology; 21 Activity-development}, Language = {eng}, Mh = {Animals; Dominance, Ocular/physiology; Humans; Neural Inhibition/*physiology; Neurons/*cytology/physiology; Visual Cortex/*embryology/physiology}, Mhda = {2006/10/26 09:00}, Month = {Sep}, Number = {5}, Own = {NLM}, Pages = {524--526}, Pii = {S0896-6273(06)00644-1}, Pl = {United States}, pmid = {16950151}, Pst = {ppublish}, Pt = {Comment; Journal Article; Review}, Rf = {18}, Sb = {IM}, Status = {MEDLINE}, Title = {Subplate neurons foster inhibition}, Volume = {51}, Year = {2006}, url = {papers/Ohshiro_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.08.022}} @article{Farley:2007, Abstract = {In the adult visual cortex, multiple feature maps exist and have characteristic spatial relationships with one another. The relationships can be reproduced by "dimension-reduction" computational models, suggesting that the principles of continuity and coverage may underlie cortical map organization. However, the mechanisms responsible for establishing these relationships are unknown. We explored whether removing one feature map during development causes a coordinated reorganization of the remaining maps or whether the remaining maps are unaffected. We removed the ocular dominance map by monocular enucleation in newborn ferrets, so that single eye stimulation drove the cortex in a more spatially uniform manner in adult monocular animals compared with normal animals. Maps of orientation, spatial frequency, and retinotopy formed in monocular ferrets, but their structures and spatial relationships differed from those in normal ferrets. The wavelength of the orientation map increased, so that the average orientation gradient across the cortex decreased. The decrease in the orientation gradient in monocular animals was most prominent in the high gradient regions of the spatial frequency map, indicating a coordinated reorganization between these two maps. In monocular animals, the orthogonal relationship between the orientation and spatial frequency maps was preserved, and the orthogonal relationship between the orientation and retinotopic maps became more pronounced. These results were consistent with detailed predictions of a dimension-reduction model of cortical organization. Thus, the number of feature maps in a cortical area influences the relationships between them, and inputs to the cortex have a significant role in generating these relationships.}, Address = {Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.}, Author = {Farley, Brandon J and Yu, Hongbo and Jin, Dezhe Z and Sur, Mriganka}, Crdt = {2007/09/21 09:00}, Da = {20070920}, Date = {2007 Sep 19}, Date-Added = {2009-03-29 19:44:28 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20071011}, Edat = {2007/09/21 09:00}, Gr = {EY07023/EY/NEI NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071203}, Mh = {Animals; Brain Mapping/methods; Eye Enucleation/methods; Female; Ferrets; Nerve Net/physiology; Orientation/physiology; Pregnancy; Spatial Behavior/physiology; Visual Cortex/*physiology; Visual Pathways/*physiology}, Mhda = {2007/10/12 09:00}, Month = {Sep}, Number = {38}, Own = {NLM}, Pages = {10299--10310}, Pii = {27/38/10299}, Pl = {United States}, pmid = {17881536}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural}, Sb = {IM}, Status = {MEDLINE}, Title = {Alteration of visual input results in a coordinated reorganization of multiple visual cortex maps}, Volume = {27}, Year = {2007}, url = {papers/Farley_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2257-07.2007}} @article{Yu:2005, Abstract = {Whether general principles can explain the layouts of cortical maps remains unresolved. In primary visual cortex of ferret, the relationships between the maps of visual space and response features are predicted by a "dimension-reduction" model. The representation of visual space is anisotropic, with the elevation and azimuth axes having different magnification. This anisotropy is reflected in the orientation, ocular dominance, and spatial frequency domains, which are elongated such that their directions of rapid change, or high-gradient axes, are orthogonal to the high-gradient axis of the visual map. The feature maps are also strongly interdependent-their high-gradient regions avoid one another and intersect orthogonally where essential, so that overlap is minimized. Our results demonstrate a clear influence of the visual map on each feature map. In turn, the local representation of visual space is smooth, as predicted when many features are mapped within a cortical area.}, Address = {Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, Author = {Yu, Hongbo and Farley, Brandon J and Jin, Dezhe Z and Sur, Mriganka}, Crdt = {2005/07/26 09:00}, Da = {20050725}, Date = {2005 Jul 21}, Date-Added = {2009-03-29 19:44:28 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20051011}, Edat = {2005/07/26 09:00}, Gr = {EY07023/EY/NEI NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Anisotropy; *Brain Mapping; Diagnostic Imaging/methods; Dominance, Cerebral; Dominance, Ocular/physiology; Electrophysiology; Ferrets; Models, Neurological; Orientation/*physiology; Photic Stimulation/methods; Predictive Value of Tests; Visual Cortex/*physiology; Visual Pathways/*physiology; Visual Perception/*physiology}, Mhda = {2005/10/12 09:00}, Month = {Jul}, Number = {2}, Own = {NLM}, Pages = {267--280}, Phst = {2004/11/19 {$[$}received{$]$}; 2005/04/15 {$[$}revised{$]$}; 2005/06/02 {$[$}accepted{$]$}}, Pii = {S0896-6273(05)00516-7}, Pl = {United States}, pmid = {16039568}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {The coordinated mapping of visual space and response features in visual cortex}, Volume = {47}, Year = {2005}, url = {papers/Yu_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.06.011}} @article{Rakic:1976, Abstract = {In foetal monkey brain neuronal projections carrying input from the two eyes initially overlap; they segregate during the second half of gestation and become fully separated in subcortical visual centres and partially separated in the cortex three weeks before birth and thus before visual experience.}, Author = {Rakic, P}, Crdt = {1976/06/10 00:00}, Da = {19760901}, Date = {1976 Jun 10}, Date-Added = {2009-03-29 18:26:43 -0400}, Date-Modified = {2013-08-27 20:04:13 +0000}, Dcom = {19760901}, Edat = {1976/06/10}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {10 circuit formation; 10 Development; sensory map; topographic map; 21 Activity-development; Structure-Activity Relationship; structural remodeling; connectivity; retina; visual system; visual cortex; Neocortex; Binocular; Monocular; currOpinRvw}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Functional Laterality; Geniculate Bodies/embryology; Gestational Age; Haplorhini; Macaca mulatta; Neural Pathways/embryology; Optic Nerve/embryology; Retina/embryology; Superior Colliculi/embryology; Visual Cortex/embryology; Visual Pathways/*embryology}, Mhda = {1976/06/10 00:01}, Month = {Jun}, Number = {5560}, Own = {NLM}, Pages = {467--471}, Pl = {ENGLAND}, pmid = {819835}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Prenatal genesis of connections subserving ocular dominance in the rhesus monkey}, Volume = {261}, Year = {1976}, url = {papers/Rakic_Nature1976.pdf}} @article{Chiu:2001, Abstract = {Multi-electrode extracellular recordings in area 17 of awake behaving ferrets were conducted to characterize the pattern of spontaneous activity in the developing visual cortex before eye opening. A linear array of 16 microwire electrodes was used to record extracellular neuronal activity across a 3.2 mm strip of visual cortex between postnatal days 22 and 28. Whereas synchronous bursts of activity were observed at all recording sites, cross-correlation analysis revealed that the timing of spike activity at all electrodes was not precisely correlated. Correlated activity between cortical sites exhibited a patchy organization having long-range components. Long-range correlated activity was observed between cortical patches that were separated by a mean distance of 1 mm. The spatial pattern of correlated activity persisted during transient lateral geniculate nucleus (LGN) activity block, indicating that long-range correlated activity is generated by intrinsic circuits within the cortex, independent of LGN input activity. These results demonstrate an innate patchy organization of correlated spontaneous activity within the cortex during the early development of cortical functional and anatomical organization.}, Address = {Interdepartmental Program in Neuroscience and Department of Brain and Cognitive Sciences, University of Rochester, Rochester, New York 14627, USA.}, Author = {Chiu, C and Weliky, M}, Crdt = {2001/11/08 10:00}, Da = {20011107}, Date = {2001 Nov 15}, Date-Added = {2009-03-29 18:05:28 -0400}, Date-Modified = {2009-04-05 13:13:25 -0400}, Dcom = {20011204}, Edat = {2001/11/08 10:00}, Gr = {EY12494/EY/NEI NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development; 21 Cortical oscillations}, Language = {eng}, Lr = {20071115}, Mh = {Action Potentials/*physiology; Aging/physiology; Animals; Axotomy; Electrodes, Implanted; Ferrets; Geniculate Bodies/physiology; Male; Optic Nerve/physiology; Periodicity; Signal Processing, Computer-Assisted; Statistics as Topic; Time Factors; Visual Cortex/*growth \& development/*physiology; Wakefulness}, Mhda = {2002/01/05 10:01}, Month = {Nov}, Number = {22}, Own = {NLM}, Pages = {8906--8914}, Pii = {21/22/8906}, Pl = {United States}, pmid = {11698602}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {J Neurosci. 2001 Nov 15;21(22):8906-14.}, Status = {MEDLINE}, Title = {Spontaneous activity in developing ferret visual cortex in vivo}, Volume = {21}, Year = {2001}, url = {papers/Chiu_JNeurosci2001.pdf}} @article{White:2001a, Abstract = {Sensory experience begins when neural circuits in the cerebral cortex are still immature; however, the contribution of experience to cortical maturation remains unclear. In the visual cortex, the selectivity of neurons for oriented stimuli at the time of eye opening is poor and increases dramatically after the onset of visual experience. Here we investigate whether visual experience has a significant role in the maturation of orientation selectivity and underlying cortical circuits using two forms of deprivation: dark rearing, which completely eliminates experience, and binocular lid suture, which alters the pattern of sensory driven activity. Orientation maps were present in dark-reared ferrets, but fully mature levels of tuning were never attained. In contrast, only rudimentary levels of orientation selectivity were observed in lid-sutured ferrets. Despite these differences, horizontal connections in both groups were less extensive and less clustered than normal, suggesting that long-range cortical processing is not essential for the expression of orientation selectivity, but may be needed for the full maturation of tuning. Thus, experience is beneficial or highly detrimental to cortical maturation, depending on the pattern of sensory driven activity.}, Address = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. white033@mc.duke.edu}, Author = {White, L E and Coppola, D M and Fitzpatrick, D}, Crdt = {2001/06/29 10:00}, Da = {20010628}, Date = {2001 Jun 28}, Date-Added = {2009-03-29 18:05:28 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20010719}, Edat = {2001/06/29 10:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20031114}, Mh = {Animals; Brain Mapping; Darkness; Diagnostic Imaging; Electrophysiology; Eyelids; Female; Ferrets; Learning; Male; Neural Pathways; Orientation/*physiology; Sensation/*physiology; Sensory Deprivation; Visual Cortex/growth \& development/*physiology; Visual Perception/*physiology}, Mhda = {2001/07/20 10:01}, Month = {Jun}, Number = {6841}, Own = {NLM}, Pages = {1049--1052}, Pii = {35082568}, Pl = {England}, pmid = {11429605}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Source = {Nature. 2001 Jun 28;411(6841):1049-52.}, Status = {MEDLINE}, Title = {The contribution of sensory experience to the maturation of orientation selectivity in ferret visual cortex}, Volume = {411}, Year = {2001}, url = {papers/White_Nature2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35082568}} @article{Ruthazer:1999, Abstract = {Thalamocortical afferents in the visual cortex of the adult sable ferret are segregated into eye-specific ocular dominance bands. The development of ocular dominance bands was studied by transneuronal labeling of the visual cortices of ferret kits between the ages of postnatal day 28 (P28) and P81 after intravitreous injections of either tritiated proline or wheat germ agglutinin-horseradish peroxidase. Laminar specificity was evident in the youngest animals studied and was similar to that in the adult by P50. In P28 and P30 ferret kits, no modulation reminiscent of ocular dominance bands was detectable in the pattern of labeling along layer IV. By P37 a slight fluctuation in the density of labeling in layer IV was evident in serial reconstructions. By P50, the amplitude of modulation had increased considerably but the pattern of ocular dominance bands did not yet appear mature. The pattern and degree of modulation of the ocular dominance bands resembled that in adult animals by P63. Flat mounts of cortex and serial reconstructions of layer IV revealed an unusual arrangement of inputs serving the two eyes in the region rostral to the periodic ocular dominance bands. In this region, inputs serving the contralateral eye were commonly fused along a mediolateral axis, rostral to which were large and sometimes fused patches of ipsilateral input.}, Address = {Keck Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco 94143-0444, USA.}, Author = {Ruthazer, E S and Baker, G E and Stryker, M P}, Crdt = {1999/04/23 02:02}, Da = {19990607}, Date = {1999 May 3}, Date-Added = {2009-03-29 18:05:28 -0400}, Date-Modified = {2009-03-29 18:06:47 -0400}, Dcom = {19990607}, Edat = {1999/04/23 02:02}, Gr = {EY02874/EY/NEI NIH HHS/United States; EY07120/EY/NEI NIH HHS/United States; R37 EY002874-20/EY/NEI NIH HHS/United States}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081121}, Mh = {Aging/physiology; Animals; Axonal Transport; Dominance, Cerebral; Ferrets/*growth \& development; Functional Laterality; Proline; Thalamus/growth \& development/physiology; Tritium; Vision, Ocular/physiology; Visual Cortex/*growth \& development/physiology; Visual Pathways/*growth \& development/physiology; Visual Perception/physiology; Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate}, Mhda = {2000/06/20 09:00}, Mid = {NIHMS50148}, Month = {May}, Number = {2}, Oid = {NLM: NIHMS50148; NLM: PMC2453001}, Own = {NLM}, Pages = {151--165}, Pii = {10.1002/(SICI)1096-9861(19990503)407:2<151::AID-CNE1>3.0.CO;2-1}, Pl = {UNITED STATES}, Pmc = {PMC2453001}, pmid = {10213088}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate); 10028-17-8 (Tritium); 147-85-3 (Proline)}, Sb = {IM}, Source = {J Comp Neurol. 1999 May 3;407(2):151-65.}, Status = {MEDLINE}, Title = {Development and organization of ocular dominance bands in primary visual cortex of the sable ferret}, Volume = {407}, Year = {1999}, url = {papers/Ruthazer_JCompNeurol1999.pdf}} @article{Chapman:1996, Abstract = {The development of orientation preference maps was studied in ferret primary visual cortex using chronic optical imaging of intrinsic signals. The emergence and maturation of the maps were examined over time in single animals. The earliest age at which cortical domains selectively responsive to particular stimulus orientations were observed varied considerably between individuals, from postnatal day 31 to 36. In all cases, the earliest maps seen were low-contrast, with regions of orientation-specific activity that were difficult to distinguish from noise. These early maps matured over a period of several days into the high-contrast, patchy maps typical of adult animals. The structure of the orientation maps was remarkably constant over time. The indistinct features in the earliest maps were always patches of the same sizes and shapes and at the same locations as in the maps obtained in subsequent recording sessions. Details of the more mature maps, including the relative intensities of individual iso-orientation domains, were also constant from one recording session to another over periods of several weeks. The patterning of iso-orientation domains in ferret primary visual cortex thus is established early in development and remains stable over time, unaffected by either normal visual experience or the anatomical rearrangements of geniculocortical afferents into eye-specific domains.}, Address = {Max Planck Institute for Psychiatry, Munich-Martinsried, Germany.}, Author = {Chapman, B and Stryker, M P and Bonhoeffer, T}, Crdt = {1996/10/15 00:00}, Da = {19961127}, Date = {1996 Oct 15}, Date-Added = {2009-03-29 18:05:28 -0400}, Date-Modified = {2009-03-29 18:06:47 -0400}, Dcom = {19961127}, Edat = {1996/10/15}, Gr = {EY09760/EY/NEI NIH HHS/United States; R01 EY011369-11/EY/NEI NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20090123}, Mh = {Age Distribution; Animals; Animals, Newborn/*physiology; Brain Mapping; Ferrets; Orientation/*physiology; Visual Cortex/*physiology}, Mhda = {1996/10/15 00:01}, Month = {Oct}, Number = {20}, Own = {NLM}, Pages = {6443--6453}, Pl = {UNITED STATES}, pmid = {8815923}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Development of orientation preference maps in ferret primary visual cortex}, Volume = {16}, Year = {1996}, url = {papers/Chapman_JNeurosci1996.pdf}} @article{Huberman:2006, Abstract = {The mechanisms that give rise to ocular dominance columns (ODCs) during development are controversial. Early experiments indicated a key role for retinal activity in ODC formation. However, later studies showed that in those early experiments, the retinal activity perturbation was initiated after ODCs had already formed. Moreover, recent studies concluded that early eye removals do not impact ODC segregation. Here we blocked spontaneous retinal activity during the very early stages of ODC development. This permanently disrupted the anatomical organization of ODCs and led to a dramatic increase in receptive field size for binocular cells in primary visual cortex. Our data suggest that early spontaneous retinal activity conveys crucial information about whether thalamocortical axons represent one or the other eye and that this activity mediates binocular competition important for shaping receptive fields in primary visual cortex.}, Address = {Center for Neuroscience, University of California, Davis, Davis, California 95616, USA.}, Author = {Huberman, Andrew D and Speer, Colenso M and Chapman, Barbara}, Cin = {Neuron. 2006 Oct 19;52(2):221-2. PMID: 17046683}, Crdt = {2006/10/19 09:00}, Da = {20061018}, Date = {2006 Oct 19}, Date-Added = {2009-03-29 18:00:20 -0400}, Date-Modified = {2013-05-21 20:36:03 +0000}, Dcom = {20070105}, Edat = {2006/10/19 09:00}, Gr = {EY11369/EY/NEI NIH HHS/United States; R01 EY011369-11/EY/NEI NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal wave paper; Spontaneous activity; Structure-Activity Relationship; topographic map; Ferrets; currOpinRvw}, Language = {eng}, Lr = {20090227}, Mh = {Action Potentials/*physiology; Aging/physiology; Animals; Animals, Newborn; Bicyclo Compounds, Heterocyclic/pharmacology; Cell Communication/physiology; Cell Differentiation/physiology; Cues; Dominance, Ocular/*physiology; Ferrets; Geniculate Bodies/cytology/growth \& development; Neuronal Plasticity/physiology; Nicotinic Agonists/pharmacology; Pyridines/pharmacology; Retina/cytology/*growth \& development; Synaptic Transmission/physiology; Vision, Binocular/*physiology; Visual Cortex/cytology/*growth \& development; Visual Fields/physiology; Visual Pathways/cytology/*growth \& development}, Mhda = {2007/01/06 09:00}, Mid = {NIHMS83819}, Month = {Oct}, Number = {2}, Oid = {NLM: NIHMS83819; NLM: PMC2647846}, Own = {NLM}, Pages = {247-254}, Phst = {2005/08/10 {$[$}received{$]$}; 2006/06/15 {$[$}revised{$]$}; 2006/07/26 {$[$}accepted{$]$}}, Pii = {S0896-6273(06)00625-8}, Pl = {United States}, Pmc = {PMC2647846}, pmid = {17046688}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Rn = {0 (Bicyclo Compounds, Heterocyclic); 0 (Nicotinic Agonists); 0 (Pyridines); 140111-52-0 (epibatidine)}, Sb = {IM}, Status = {MEDLINE}, Title = {Spontaneous retinal activity mediates development of ocular dominance columns and binocular receptive fields in v1}, Volume = {52}, Year = {2006}, url = {papers/Huberman_Neuron2006.pdf}, Bdsk-File-2 = {papers/Huberman_Neuron2006a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.07.028}} @article{Li:2006, Abstract = {Development of the selective response properties that define columns in sensory cortex is thought to begin early in cortical maturation, without the need for experience. We investigated the development of direction selectivity in ferret visual cortex using optical imaging and electrophysiological techniques and found an exception to this view. Unlike orientation selectivity and ocular dominance, direction selectivity was not detected at eye opening. Direction selectivity emerged several days later and strengthened to adult levels over the following 2 weeks. Visual experience was essential for this process, as shown by the absence of direction selectivity in dark-reared ferrets. The impairment persisted in dark-reared ferrets that were given experience after this period, despite the recovery of response amplitude, preference and bandwidth for stimulus orientation, spatial and temporal frequency, and contrast. Visual experience in early postnatal life plays a necessary and unique role in the development of cortical direction selectivity.}, Address = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.}, Author = {Li, Ye and Fitzpatrick, David and White, Leonard E}, Cin = {Nat Neurosci. 2006 May;9(5):591-2. PMID: 16639402}, Crdt = {2006/04/11 09:00}, Da = {20060426}, Date = {2006 May}, Date-Added = {2009-03-29 18:00:20 -0400}, Date-Modified = {2013-08-28 14:53:25 +0000}, Dcom = {20060804}, Dep = {20060409}, Edat = {2006/04/11 09:00}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development; ferret; topographic map; visual system; Visual Cortex; neurophysiology; in vivo; intrinsic signal; optical imaging; currOpinRvw}, Language = {eng}, Lr = {20061115}, Mh = {Action Potentials/physiology; Animals; Animals, Newborn; Behavior, Animal; Contrast Sensitivity/physiology; Diagnostic Imaging/methods; Female; Ferrets; Learning/*physiology; Male; *Orientation; Photic Stimulation/methods; Sensory Deprivation/physiology; Space Perception/*physiology; Visual Cortex/*physiology; Visual Pathways/*growth \& development}, Mhda = {2006/08/05 09:00}, Month = {May}, Number = {5}, Own = {NLM}, Pages = {676--681}, Phst = {2006/01/20 {$[$}received{$]$}; 2006/03/16 {$[$}accepted{$]$}; 2006/04/09 {$[$}aheadofprint{$]$}}, Pii = {nn1684}, Pl = {United States}, pmid = {16604068}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {The development of direction selectivity in ferret visual cortex requires early visual experience}, Volume = {9}, Year = {2006}, url = {papers/Li_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1684}} @article{Feller:2005, Abstract = {One of the seminal discoveries in developmental neuroscience is that altering visual experience through monocular deprivation can alter both the physiological and the anatomical representation of the two eyes, called ocular dominance columns, in primary visual cortex. This rearrangement is restricted to a critical period that starts a few days or weeks after vision is established and ends before adulthood. In contrast to the original hypothesis proposed by Hubel and Wiesel, ocular dominance columns are already substantially formed before the onset of the critical period. Indeed, before the critical period there is a period of ocular dominance column formation during which there is robust spontaneous activity and visual experience. Recent findings raise important questions about whether activity guides ocular dominance column formation in this 'precritical period'. One developmental event that marks the passage from the precritical period to the critical period is the activation of a GABAergic circuit. How these events trigger the transition from the precritical to critical period is not known.}, Address = {Neurobiology Section 0357, UCSD, 9500 Gilman Drive, La Jolla, CA 92093-0357, USA. mscanziani@ucsd.edu}, Author = {Feller, Marla B and Scanziani, Massimo}, Crdt = {2005/02/22 09:00}, Da = {20050221}, Date = {2005 Feb}, Date-Added = {2009-03-29 18:00:20 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Dcom = {20050429}, Edat = {2005/02/22 09:00}, Gr = {MH 70058/MH/NIMH NIH HHS/United States; MH71401/MH/NIMH NIH HHS/United States; NS13528-01A1/NS/NINDS NIH HHS/United States}, Issn = {0959-4388 (Print)}, Jid = {9111376}, Journal = {Curr Opin Neurobiol}, Jt = {Current opinion in neurobiology}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal wave paper; currOpinRvw}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Dominance, Ocular/*physiology; Humans; Neuronal Plasticity/*physiology; Visual Cortex/*growth \& development/physiology}, Mhda = {2005/04/30 09:00}, Month = {Feb}, Number = {1}, Own = {NLM}, Pages = {94--100}, Pii = {S0959-4388(05)00013-9}, Pl = {England}, pmid = {15721750}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {65}, Sb = {IM}, Status = {MEDLINE}, Title = {A precritical period for plasticity in visual cortex}, Volume = {15}, Year = {2005}, url = {papers/Feller_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.01.012}} @article{Katz:2002a, Abstract = {The development of ocular dominance columns has served as a Rosetta stone for understanding the mechanisms that guide the construction of cortical circuits. Traditionally, the emergence of ocular dominance columns was thought to be closely tied to the critical period, during which columnar architecture is highly susceptible to alterations in visual input. However, recent findings in cats, monkeys and ferrets indicate that columns develop far earlier, more rapidly and with considerably greater precision than was previously suspected. These observations indicate that the initial establishment of cortical functional architecture, and its subsequent plasticity during the critical period, are distinct developmental phases that might reflect distinct mechanisms.}, Address = {Howard Hughes Medical Institute and Department of Neurobiology, Box 3209, Duke University Medical Center, Durham, North Carolina 27710, USA. larry@neuro.duke.edu}, Author = {Katz, Lawrence C and Crowley, Justin C}, Crdt = {2002/02/02 10:00}, Da = {20020201}, Date = {2002 Jan}, Date-Added = {2009-03-29 18:00:20 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20020221}, Edat = {2002/02/02 10:00}, Issn = {1471-003X (Print)}, Jid = {100962781}, Journal = {Nat Rev Neurosci}, Jt = {Nature reviews. Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20060222}, Mh = {Animals; Dominance, Ocular/*physiology; Models, Biological; Retina/cytology/physiology; Thalamus/physiology; Visual Cortex/cytology/growth \& development/*physiology; Visual Pathways; Visual Perception/*physiology}, Mhda = {2002/02/22 10:01}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {34--42}, Pii = {nrn703}, Pl = {England}, pmid = {11823803}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {107}, Sb = {IM}, Status = {MEDLINE}, Title = {Development of cortical circuits: lessons from ocular dominance columns}, Volume = {3}, Year = {2002}, url = {papers/Katz_NatRevNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn703}} @article{Daw:1978, Abstract = {The critical period for modifying the preferred direction in cat cortical units occurs earlier than that for monocular deprivation. The independence of the effects of these two types of deprivation from each other was tested by rearing six kittens with both reverse suture and reversed directional deprivation. The kittens were placed in a drum rotating in one direction with one eye open at ages 2 1/2 to 5 weeks; the drum rotation was reversed and the other eye opened when they were 5 to 12 weeks old. Recordings were then made in the visual cortex. The results were the sum of the effects of reverse suture and reversal of directional deprivation: most cells were driven by the eye that was open second, and most unidirectional cells preferred the direction to which the animals were exposed first. Consequently, many unidirectional cells preferred the first direction but were driven by the eye open second--a combination that the animal never saw during rearing. There was also an effect of ocular deprivation on directional properties and vice versa: reverse suture reduced the overall percentage of unidirectional cells, just as directional deprivation has been shown to affect the ocular dominance histogram. This result suggests that the same cells may be affected by both forms of deprivation.}, Author = {Daw, N W and Berman, N E and Ariel, M}, Crdt = {1978/02/03 00:00}, Da = {19780321}, Date = {1978 Feb 3}, Date-Added = {2009-03-29 15:39:06 -0400}, Date-Modified = {2009-03-29 15:40:54 -0400}, Dcom = {19780321}, Edat = {1978/02/03}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081121}, Mh = {Age Factors; Animals; Cats; Cell Differentiation; Functional Laterality; Motion Perception/physiology; *Vision, Ocular; Visual Cortex/cytology/*growth \& development; Visual Pathways/growth \& development; Visual Perception/physiology}, Mhda = {1978/02/03 00:01}, Month = {Feb}, Number = {4328}, Own = {NLM}, Pages = {565--567}, Pl = {UNITED STATES}, pmid = {622560}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Interaction of critical periods in the visual cortex of kittens}, Volume = {199}, Year = {1978}, url = {papers/Daw_Science1978.pdf}} @article{Huang:1999, Abstract = {Maturation of the visual cortex is influenced by visual experience during an early postnatal period. The factors that regulate such a critical period remain unclear. We examined the maturation and plasticity of the visual cortex in transgenic mice in which the postnatal rise of brain-derived neurotrophic factor (BDNF) was accelerated. In these mice, the maturation of GABAergic innervation and inhibition was accelerated. Furthermore, the age-dependent decline of cortical long-term potentiation induced by white matter stimulation, a form of synaptic plasticity sensitive to cortical inhibition, occurred earlier. Finally, transgenic mice showed a precocious development of visual acuity and an earlier termination of the critical period for ocular dominance plasticity. We propose that BDNF promotes the maturation of cortical inhibition during early postnatal life, thereby regulating the critical period for visual cortical plasticity.}, Address = {Center for Learning and Memory, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA.}, Author = {Huang, Z J and Kirkwood, A and Pizzorusso, T and Porciatti, V and Morales, B and Bear, M F and Maffei, L and Tonegawa, S}, Crdt = {1999/09/28 00:00}, Da = {19991015}, Date = {1999 Sep 17}, Date-Added = {2009-03-28 00:52:09 -0400}, Date-Modified = {2009-03-28 00:52:47 -0400}, Dcom = {19991015}, Edat = {1999/09/28}, Gr = {NS32925/NS/NINDS NIH HHS/United States; R01EY12124-01/EY/NEI NIH HHS/United States}, Issn = {0092-8674 (Print)}, Jid = {0413066}, Journal = {Cell}, Jt = {Cell}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Age Factors; Animals; Animals, Newborn; Base Sequence; Brain-Derived Neurotrophic Factor/*physiology; Cerebral Cortex/physiology; Evoked Potentials; Interneurons; Long-Term Potentiation; Mice; Mice, Transgenic; Molecular Sequence Data; Neural Inhibition/*physiology; Neuronal Plasticity/*physiology; Parvalbumins/isolation \& purification; Perception/physiology; Prosencephalon/physiology; Pyramidal Cells; *Receptors, GABA; Recombinant Proteins/metabolism; Time Factors; Tissue Distribution; Transgenes; Visual Acuity; Visual Cortex/*physiology}, Mhda = {1999/09/28 00:01}, Month = {Sep}, Number = {6}, Own = {NLM}, Pages = {739--755}, Pii = {S0092-8674(00)81509-3}, Pl = {UNITED STATES}, pmid = {10499792}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Brain-Derived Neurotrophic Factor); 0 (Parvalbumins); 0 (Receptors, GABA); 0 (Recombinant Proteins)}, Sb = {IM}, Source = {Cell. 1999 Sep 17;98(6):739-55.}, Status = {MEDLINE}, Title = {BDNF regulates the maturation of inhibition and the critical period of plasticity in mouse visual cortex}, Volume = {98}, Year = {1999}, url = {papers/Huang_Cell1999.pdf}} @article{Iwai:2003, Abstract = {Mice lacking a synaptic isoform of glutamic acid decarboxylase (GAD65) do not exhibit ocular dominance plasticity unless an appropriate level of GABAergic transmission is restored by direct infusion of benzodiazepines into the brain. To better understand how intracortical inhibition triggers experience-dependent changes, we dissected the precise timing requirement for GABA function in the monocular deprivation (MD) paradigm. Diazepam (DZ) or vehicle solution was infused daily before and/or during 4 d of MD in GAD65 knock-out mice. Extracellular single-unit recordings from the binocular zone of visual cortex were performed at the end of deprivation. We found that a minimum treatment of 2 d near the beginning of MD was sufficient to fully activate plasticity but did not need to overlap the deprivation per se. Extended delay after DZ infusion eventually led to loss of plasticity accompanied by improved intrinsic inhibitory circuit function. Two day DZ treatment just after eye opening similarly closed the critical period prematurely in wild-type mice. Raising wild-type mice in complete darkness from birth delayed the peak sensitivity to MD as in other mammals. Interestingly, 2 d DZ infusion in the dark also closed the critical period, whereas equally brief light exposure during dark-rearing had no such effect. Thus, enhanced tonic signaling through GABA(A) receptors rapidly creates a milieu for plasticity within neocortex capable of triggering a critical period for ocular dominance independent of visual experience itself.}, Address = {Laboratory for Neuronal Circuit Development, The Institute of Physical and Chemical Research (RIKEN) Brain Science Institute, Saitama 351-0198, Japan.}, Author = {Iwai, Youichi and Fagiolini, Michela and Obata, Kunihiko and Hensch, Takao K}, Crdt = {2003/08/02 05:00}, Da = {20030731}, Date = {2003 Jul 30}, Date-Added = {2009-03-28 00:39:29 -0400}, Date-Modified = {2009-03-28 00:39:55 -0400}, Dcom = {20030903}, Edat = {2003/08/02 05:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071024}, Mh = {Animals; *Critical Period (Psychology); Darkness; Diazepam/pharmacology; GABA Modulators/pharmacology; Glutamate Decarboxylase/deficiency/genetics; Isoenzymes/deficiency/genetics; Mice; Mice, Inbred C57BL; Mice, Knockout; Neural Inhibition/drug effects/*physiology; Neuronal Plasticity/drug effects/physiology; Photic Stimulation/methods; Receptors, GABA-A/drug effects/metabolism; Sensory Deprivation/physiology; Synaptic Transmission/drug effects/genetics/physiology; Time Factors; Visual Cortex/drug effects/*physiology}, Mhda = {2003/09/04 05:00}, Month = {Jul}, Number = {17}, Own = {NLM}, Pages = {6695--6702}, Pii = {23/17/6695}, Pl = {United States}, pmid = {12890762}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (GABA Modulators); 0 (Isoenzymes); 0 (Receptors, GABA-A); 439-14-5 (Diazepam); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 2)}, Sb = {IM}, Status = {MEDLINE}, Title = {Rapid critical period induction by tonic inhibition in visual cortex}, Volume = {23}, Year = {2003}, url = {papers/Iwai_JNeurosci2003.pdf}} @article{Fagiolini:2000, Abstract = {Neuronal circuits across several systems display remarkable plasticity to sensory input during postnatal development. Experience-dependent refinements are often restricted to well-defined critical periods in early life, but how these are established remains mostly unknown. A representative example is the loss of responsiveness in neocortex to an eye deprived of vision. Here we show that the potential for plasticity is retained throughout life until an inhibitory threshold is attained. In mice of all ages lacking an isoform of GABA (gamma-aminobutyric acid) synthetic enzyme (GAD65), as well as in immature wild-type animals before the onset of their natural critical period, benzodiazepines selectively reduced a prolonged discharge phenotype to unmask plasticity. Enhancing GABA-mediated transmission early in life rendered mutant animals insensitive to monocular deprivation as adults, similar to normal wild-type mice. Short-term presynaptic dynamics reflected a synaptic reorganization in GAD65 knockout mice after chronic diazepam treatment. A threshold level of inhibition within the visual cortex may thus trigger, once in life, an experience-dependent critical period for circuit consolidation, which may otherwise lie dormant.}, Address = {Laboratory for Neuronal Circuit Development, Brain Science Institute RIKEN, Saitama, Japan.}, Author = {Fagiolini, M and Hensch, T K}, Crdt = {2000/03/21 09:00}, Da = {20000407}, Date = {2000 Mar 9}, Date-Added = {2009-03-28 00:38:32 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20000407}, Edat = {2000/03/21 09:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20031114}, Mh = {Aging/*physiology; Animals; Critical Period (Psychology); Diazepam/administration \& dosage; Haplorhini; Mice; Mice, Inbred C57BL; Mice, Knockout; *Neuronal Plasticity/drug effects; Sensory Deprivation; Visual Cortex/drug effects/*physiology; Visual Perception/*physiology; gamma-Aminobutyric Acid/metabolism}, Mhda = {2001/03/23 10:01}, Month = {Mar}, Number = {6774}, Own = {NLM}, Pages = {183--186}, Pl = {ENGLAND}, pmid = {10724170}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {439-14-5 (Diazepam); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM; S}, Status = {MEDLINE}, Title = {Inhibitory threshold for critical-period activation in primary visual cortex}, Volume = {404}, Year = {2000}, url = {papers/Fagiolini_Nature2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35004582}} @article{Hensch:2004a, Abstract = {Neuronal circuits are shaped by experience during critical periods of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally accessible, especially in the developing visual system. This review summarizes our current understanding of known critical periods across several systems and species. It delineates a number of emerging principles: functional competition between inputs, role for electrical activity, structural consolidation, regulation by experience (not simply age), special role for inhibition in the CNS, potent influence of attention and motivation, unique timing and duration, as well as use of distinct molecular mechanisms across brain regions and the potential for reactivation in adulthood. A deeper understanding of critical periods will open new avenues to "nurture the brain"-from international efforts to link brain science and education to improving recovery from injury and devising new strategies for therapy and lifelong learning.}, Address = {Laboratory for Neuronal Circuit Development, Critical Period Mechanisms Research Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. hensch@riken.jp}, Author = {Hensch, Takao K}, Crdt = {2004/06/26 05:00}, Da = {20040625}, Date = {2004}, Date-Added = {2009-03-28 00:35:50 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20041013}, Edat = {2004/06/26 05:00}, Issn = {0147-006X (Print)}, Jid = {7804039}, Journal = {Annu Rev Neurosci}, Jt = {Annual review of neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20041117}, Mh = {Age Factors; Animals; Brain/cytology/growth \& development/*physiology; Cell Communication/physiology; Cell Differentiation/*physiology; *Critical Period (Psychology); Cues; Humans; Learning/physiology; Neural Pathways/cytology/growth \& development/*physiology; Neuronal Plasticity/*physiology; Synapses/physiology; Synaptic Transmission/physiology}, Mhda = {2004/10/14 09:00}, Own = {NLM}, Pages = {549--579}, Pl = {United States}, pmid = {15217343}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {234}, Sb = {IM}, Status = {MEDLINE}, Title = {Critical period regulation}, Volume = {27}, Year = {2004}, url = {papers/Hensch_AnnuRevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.27.070203.144327}} @article{Linkenhoker:2002, Abstract = {The plasticity in the central nervous system that underlies learning is generally more restricted in adults than in young animals. In one well-studied example, the auditory localization pathway has been shown to be far more limited in its capacity to adjust to abnormal experience in adult than in juvenile barn owls. Plasticity in this pathway has been induced by exposing owls to prismatic spectacles that cause a large, horizontal shift of the visual field. With prisms, juveniles learn new associations between auditory cues, such as interaural time difference (ITD), and locations in visual space, and acquire new neurophysiological maps of ITD in the optic tectum, whereas adults do neither. Here we show that when the prismatic shift is experienced in small increments, maps of ITD in adults do change adaptively. Once established through incremental training, new ITD maps can be reacquired with a single large prismatic shift. Our results show that there is a substantially greater capacity for plasticity in adults than was previously recognized and highlight a principled strategy for tapping this capacity that could be applied in other areas of the adult central nervous system.}, Address = {Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125, USA.}, Author = {Linkenhoker, Brie A and Knudsen, Eric I}, Cin = {Nature. 2002 Sep 19;419(6904):258-9. PMID: 12239549}, Crdt = {2002/09/20 10:00}, Da = {20020919}, Date = {2002 Sep 19}, Date-Added = {2009-03-27 19:40:45 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20021021}, Edat = {2002/09/20 10:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Acoustic Stimulation; Adaptation, Physiological; Aging/*physiology; Animals; Auditory Pathways/physiology; Auditory Perception/*physiology; Cues; Electrophysiology; Learning/*physiology; Neuronal Plasticity/*physiology; Space Perception/*physiology; Strigiformes/*physiology; Superior Colliculi/*physiology; Time Factors; Visual Fields/physiology}, Mhda = {2002/10/22 04:00}, Month = {Sep}, Number = {6904}, Own = {NLM}, Pages = {293--296}, Pii = {nature01002}, Pl = {England}, pmid = {12239566}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM; S}, Source = {Nature. 2002 Sep 19;419(6904):293-6.}, Status = {MEDLINE}, Title = {Incremental training increases the plasticity of the auditory space map in adult barn owls}, Volume = {419}, Year = {2002}, url = {papers/Linkenhoker_Nature2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01002}} @article{Knudsen:2002, Abstract = {A bird sings and you turn to look at it a process so automatic it seems simple. But is it? Our ability to localize the source of a sound relies on complex neural computations that translate auditory localization cues into representations of space. In barn owls, the visual system is important in teaching the auditory system how to translate cues. This example of instructed plasticity is highly quantifiable and demonstrates mechanisms and principles of learning that may be used widely throughout the central nervous system.}, Address = {Department of Neurobiology, Stanford University School of Medicine, CA 94305, USA. eknudsen@stanford.edu}, Author = {Knudsen, Eric I}, Crdt = {2002/05/17 10:00}, Da = {20020516}, Date = {2002 May 16}, Date-Added = {2009-03-27 19:40:45 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20020610}, Edat = {2002/05/17 10:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Aging/physiology; Animals; Auditory Perception/*physiology; Brain/*physiology; Cues; Learning/*physiology; Neuronal Plasticity/physiology; Orientation/physiology; Receptors, GABA/metabolism; Receptors, N-Methyl-D-Aspartate/metabolism; Space Perception/physiology; Strigiformes/*physiology}, Mhda = {2002/06/11 10:01}, Month = {May}, Number = {6886}, Own = {NLM}, Pages = {322--328}, Pii = {417322a}, Pl = {England}, pmid = {12015612}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {72}, Rn = {0 (Receptors, GABA); 0 (Receptors, N-Methyl-D-Aspartate)}, Sb = {IM}, Source = {Nature. 2002 May 16;417(6886):322-8.}, Status = {MEDLINE}, Title = {Instructed learning in the auditory localization pathway of the barn owl}, Volume = {417}, Year = {2002}, url = {papers/Knudsen_Nature2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/417322a}} @article{Hyde:2002, Abstract = {The midbrain contains an auditory map of space that is shaped by visual experience. When barn owls are raised wearing spectacles that horizontally displace the visual field, the auditory space map in the external nucleus of the inferior colliculus (ICX) shifts according to the optical displacement of the prisms. Topographic visual activity in the optic tectum could serve as the template that instructs the auditory space map. We studied the effects of a restricted, unilateral lesion in the portion of the optic tectum that represents frontal space. Here we show that such a lesion eliminates adaptive adjustments specifically in the portion of the auditory map that represents frontal space on the same side of the brain, while the rest of the map continues to adjust adaptively. Thus, activity in the tectum calibrates the auditory space map in a location-specific manner. Because the site of adaptive changes is the ICX, the results also indicate that the tectum provides a topographic instructive signal that controls adaptive auditory plasticity in the ICX.}, Address = {Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305, USA.}, Author = {Hyde, Peter S and Knudsen, Eric I}, Cin = {Nature. 2002 Jan 3;415(6867):29-31. PMID: 11780099}, Crdt = {2002/01/10 10:00}, Da = {20020107}, Date = {2002 Jan 3}, Date-Added = {2009-03-27 19:40:45 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20020129}, Edat = {2002/01/10 10:00}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {Adaptation, Physiological/*physiology; Animals; Auditory Perception/*physiology; Brain Mapping; Cues; Electrophysiology; Eyeglasses; Neuronal Plasticity/*physiology; Space Perception/*physiology; Strigiformes/*physiology; Superior Colliculi/pathology/*physiology; Vision, Ocular/*physiology; Visual Fields; Visual Perception/physiology}, Mhda = {2002/01/30 10:01}, Month = {Jan}, Number = {6867}, Own = {NLM}, Pages = {73--76}, Pii = {415073a}, Pl = {England}, pmid = {11780119}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {The optic tectum controls visually guided adaptive plasticity in the owl's auditory space map}, Volume = {415}, Year = {2002}, url = {papers/Hyde_Nature2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/415073a}} @article{Galli:1988, Abstract = {The existence of spontaneous neural activity in mammalian retinal ganglion cells during prenatal life has long been suspected. This activity could play a key role in the refinement of retinal projections during development. Recordings in vivo from the retinas of rat fetuses between embryonic day 17 and 21 found action potentials in spontaneously active ganglion cells at all the ages studied.}, Address = {Istituto di Neurofisiologia Consiglio Nazionale Delle Richerche via San Zeno, Pisa, Italy.}, Author = {Galli, L and Maffei, L}, Crdt = {1988/10/07 00:00}, Da = {19881110}, Date = {1988 Oct 7}, Date-Added = {2009-03-27 18:56:11 -0400}, Date-Modified = {2010-10-01 05:58:13 -0400}, Dcom = {19881110}, Edat = {1988/10/07}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; 21 Neurophysiology; retinal wave paper}, Language = {eng}, Lr = {20070319}, Mh = {Action Potentials; Animals; Electric Conductivity; Female; Fetus/physiology; Pregnancy; Rats; Retina/*embryology/*physiology; Retinal Ganglion Cells/*physiology}, Mhda = {1988/10/07 00:01}, Month = {Oct}, Number = {4875}, Own = {NLM}, Pages = {90--91}, Pl = {UNITED STATES}, pmid = {3175637}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Status = {MEDLINE}, Title = {Spontaneous impulse activity of rat retinal ganglion cells in prenatal life}, Volume = {242}, Year = {1988}, url = {papers/Galli_Science1988.pdf}} @article{Meister:1991, Abstract = {The development of orderly connections in the mammalian visual system depends on action potentials in the optic nerve fibers, even before the retina receives visual input. In particular, it has been suggested that correlated firing of retinal ganglion cells in the same eye directs the segregation of their synaptic terminals into eye-specific layers within the lateral geniculate nucleus. Such correlations in electrical activity were found by simultaneous recording of the extracellular action potentials of up to 100 ganglion cells in the isolated retina of the newborn ferret and the fetal cat. These neurons fired spikes in nearly synchronous bursts lasting a few seconds and separated by 1 to 2 minutes of silence. Individual bursts consisted of a wave of excitation, several hundred micrometers wide, sweeping across the retina at about 100 micrometers per second. These concerted firing patterns have the appropriate spatial and temporal properties to guide the refinement of connections between the retina and the lateral geniculate nucleus.}, Address = {Department of Neurobiology, Stanford University School of Medicine, CA 94305.}, Author = {Meister, M and Wong, R O and Baylor, D A and Shatz, C J}, Crdt = {1991/05/17 00:00}, Da = {19910626}, Date = {1991 May 17}, Date-Added = {2009-03-27 18:49:33 -0400}, Date-Modified = {2013-08-27 03:02:32 +0000}, Dcom = {19910626}, Edat = {1991/05/17}, Gr = {EY 05750/EY/NEI NIH HHS/United States}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal wave paper; currOpinRvw}, Language = {eng}, Lr = {20081121}, Mh = {Action Potentials/drug effects; Aging; Animals; Animals, Newborn; Calcium/pharmacology; Cats; Electrophysiology/methods; Ferrets; Retina/*growth \& development; Retinal Ganglion Cells/drug effects/*physiology; Vision, Ocular}, Mhda = {1991/05/17 00:01}, Month = {May}, Number = {5008}, Own = {NLM}, Pages = {939-943}, Pl = {UNITED STATES}, pmid = {2035024}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Rn = {7440-70-2 (Calcium)}, Sb = {IM}, Status = {MEDLINE}, Title = {Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina}, Volume = {252}, Year = {1991}, url = {papers/Meister_Science1991.pdf}} @article{Brown:2000, Abstract = {Topographic maps are a fundamental feature of sensory representations in nervous systems. The formation of one such map, defined by the connection of ganglion cells in the retina to their targets in the superior colliculus of the midbrain, is thought to depend upon an interaction between complementary gradients of retinal EphA receptors and collicular ephrin-A ligands. We have tested this hypothesis by using gene targeting to elevate EphA receptor expression in a subset of mouse ganglion cells, thereby producing two intermingled ganglion cell populations that express distinct EphA receptor gradients. We find that these two populations form separate maps in the colliculus, which can be predicted as a function of the net EphA receptor level that a given ganglion cell expresses relative to its neighbors.}, Address = {Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA.}, Author = {Brown, A and Yates, P A and Burrola, P and Ortuno, D and Vaidya, A and Jessell, T M and Pfaff, S L and O'Leary, D D and Lemke, G}, Crdt = {2000/08/10 11:00}, Da = {20000825}, Date = {2000 Jul 7}, Date-Added = {2009-03-27 18:33:10 -0400}, Date-Modified = {2009-03-27 18:33:10 -0400}, Dcom = {20000825}, Edat = {2000/08/10 11:00}, Issn = {0092-8674 (Print)}, Jid = {0413066}, Journal = {Cell}, Jt = {Cell}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Axons/metabolism/physiology; *Brain Mapping/methods; Eye Proteins/genetics/physiology; Gene Expression; Gene Targeting; Homeodomain Proteins/genetics/physiology; Mesencephalon/*physiology; Mice; Nerve Tissue Proteins/genetics/physiology; *Neural Pathways; Receptor Protein-Tyrosine Kinases/genetics/*physiology; Receptor, EphA3; Receptor, EphA5; Retina/metabolism/*physiology; Retinal Ganglion Cells/metabolism/physiology; *Signal Transduction}, Mhda = {2000/09/02 11:01}, Month = {Jul}, Number = {1}, Own = {NLM}, Pages = {77--88}, Pii = {S0092-8674(00)00012-X}, Pl = {UNITED STATES}, pmid = {10929715}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Eye Proteins); 0 (Homeodomain Proteins); 0 (Nerve Tissue Proteins); 0 (insulin gene enhancer binding protein Isl-1); EC 2.7.1.112 (Epha3 protein, mouse); EC 2.7.1.112 (Receptor Protein-Tyrosine Kinases); EC 2.7.1.112 (Receptor, EphA3); EC 2.7.1.112 (Receptor, EphA5)}, Sb = {IM}, Status = {MEDLINE}, Title = {Topographic mapping from the retina to the midbrain is controlled by relative but not absolute levels of EphA receptor signaling}, Volume = {102}, Year = {2000}, url = {papers/Brown_Cell2000.pdf}} @article{Akerman:2006, Abstract = {Neurotransmission during development regulates synaptic maturation in neural circuits, but the contribution of different neurotransmitter systems is unclear. We investigated the role of GABAA receptor-mediated Cl- conductances in the development of synaptic responses in the Xenopus visual system. Intracellular Cl- concentration ([Cl-]i) was found to be high in immature tectal neurons and then falls over a period of several weeks. GABAergic synapses are present at early stages of tectal development and, when activated by optic nerve stimulation or visual stimuli, induce sustained depolarizing Cl- conductances that facilitate retinotectal transmission by NMDA receptors. To test whether depolarizing GABAergic inputs cooperate with NMDA receptors during activity-dependent maturation of glutamatergic synapses, we prematurely reduced [Cl-]i in tectal neurons in vivo by expressing the Cl- transporter KCC2. This blocked the normal developmental increase in AMPA receptor-mediated retinotectal transmission and increased GABAergic synaptic input to tectal neurons. Therefore, depolarizing GABAergic transmission plays a pivotal role in the maturation of excitatory transmission and controls the balance of excitation and inhibition in the developing retinotectal circuit.}, Address = {Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.}, Author = {Akerman, Colin J and Cline, Hollis T}, Crdt = {2006/05/12 09:00}, Da = {20060511}, Date = {2006 May 10}, Date-Added = {2009-03-27 15:13:48 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060531}, Edat = {2006/05/12 09:00}, Gr = {Wellcome Trust/United Kingdom}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 10 circuit formation; 10 Development}, Language = {eng}, Lr = {20070813}, Mh = {Animals; Cell Membrane/physiology; Chloride Channels/*physiology; Electric Conductivity; Excitatory Postsynaptic Potentials/*physiology; Larva; Membrane Potentials/physiology; Neural Inhibition/*physiology; Synaptic Transmission/physiology; Visual Pathways/*embryology/*physiology; Xenopus laevis/*physiology; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2006/06/01 09:00}, Month = {May}, Number = {19}, Own = {NLM}, Pages = {5117--5130}, Pii = {26/19/5117}, Pl = {United States}, pmid = {16687503}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.}, Rn = {0 (Chloride Channels); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo}, Volume = {26}, Year = {2006}, url = {papers/Akerman_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0319-06.2006}} @article{Firth:2006, Abstract = {Early in development, before the retina is responsive to light, neurons exhibit spontaneous activity. Recently it was demonstrated that starburst amacrine cells, a unique class of neurons that secretes both GABA and acetylcholine, spontaneously depolarize. Networks comprised of spontaneously active starburst cells initiate correlated bursts of action potentials that propagate across the developing retina with a periodicity on the order minutes. To determine whether other retinal interneurons have similar "pacemaking" properties, we have utilized cultures of dissociated neurons from the rat retina. In the presence of antagonists for fast neurotransmitter receptors, distinct populations of neurons exhibited spontaneous, uncorrelated increases in intracellular calcium concentration. These increases in intracellular calcium concentration were sensitive to tetrodotoxin, indicating they are mediated by spontaneous membrane depolarizations. By combining immunofluorescence and calcium imaging, we found that 44% of spontaneously active neurons were GABAergic and included starburst amacrine cells. Whole cell voltage clamp recordings in the absence of antagonists for fast neurotransmitters revealed that after 7 days in culture, individual retinal neurons receive bursts of GABA-A receptor mediated synaptic input with a periodicity similar to that measured in spontaneously active GABAergic neurons. Low concentrations of GABA-A receptor antagonists did not alter the inter-burst interval despite significant reduction of post-synaptic current amplitude, indicating that pacemaker activity of GABAergic neurons was not influenced by network interactions. Together, these findings indicate that spiking GABAergic interneurons can function as pacemakers in the developing retina.}, Address = {Neurobiology Section, Division of Biological Sciences, University of California at San Diego, San Diego, California, USA.}, Author = {Firth, Sally I and Feller, Marla B}, Crdt = {2006/10/06 09:00}, Da = {20061005}, Date = {2006 Sep-Oct}, Date-Added = {2009-03-27 15:12:17 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20061212}, Edat = {2006/10/06 09:00}, Gr = {EY016417/EY/NEI NIH HHS/United States; EY13528/EY/NEI NIH HHS/United States}, Issn = {0952-5238 (Print)}, Jid = {8809466}, Journal = {Vis Neurosci}, Jt = {Visual neuroscience}, Language = {eng}, Lr = {20071115}, Mh = {2-Amino-5-phosphonovalerate/pharmacology; 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology; Action Potentials/drug effects/physiology/radiation effects; Anesthetics, Local/pharmacology; Animals; Animals, Newborn; Calcium/*metabolism; Cells, Cultured; Chelating Agents/pharmacology; Egtazic Acid/analogs \& derivatives/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Extracellular Fluid/*metabolism; GABA Antagonists/pharmacology; Immunohistochemistry/methods; Interneurons/drug effects/*metabolism; Patch-Clamp Techniques/methods; Picrotoxin/pharmacology; Pyridazines/pharmacology; Rats; Rats, Sprague-Dawley; Retina/*cytology; Superior Colliculi/cytology; Tetrodotoxin/pharmacology; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2006/12/13 09:00}, Month = {Sep-Oct}, Number = {5}, Own = {NLM}, Pages = {807--814}, Phst = {2006/03/22 {$[$}received{$]$}; 2006/06/13 {$[$}accepted{$]$}}, Pii = {S095252380623013X}, Pl = {England}, pmid = {17020635}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Anesthetics, Local); 0 (Chelating Agents); 0 (Excitatory Amino Acid Antagonists); 0 (GABA Antagonists); 0 (Pyridazines); 104104-50-9 (gabazine); 115066-14-3 (6-Cyano-7-nitroquinoxaline-2,3-dione); 124-87-8 (Picrotoxin); 139890-68-9 (1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester); 4368-28-9 (Tetrodotoxin); 56-12-2 (gamma-Aminobutyric Acid); 67-42-5 (Egtazic Acid); 7440-70-2 (Calcium); 76726-92-6 (2-Amino-5-phosphonovalerate)}, Sb = {IM}, Status = {MEDLINE}, Title = {Dissociated GABAergic retinal interneurons exhibit spontaneous increases in intracellular calcium}, Volume = {23}, Year = {2006}, url = {papers/Firth_VisNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1017/S095252380623013X}} @article{Sperry:1963, Author = {Sperry, R W}, Crdt = {1963/10/01 00:00}, Da = {19640301}, Date = {1963 Oct}, Date-Added = {2009-03-26 18:08:55 -0400}, Date-Modified = {2009-07-28 17:14:08 -0400}, Dcom = {19961201}, Edat = {1963/10/01}, Issn = {0027-8424 (Print)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {*BIOCHEMISTRY; *EXPERIMENTAL LAB STUDY; *NERVE TISSUE; *REGENERATION}, Language = {eng}, Lr = {20081121}, Mh = {Biochemical Phenomena; *Biochemistry; *Nerve Tissue; *Regeneration; *Research}, Mhda = {1963/10/01 00:01}, Month = {Oct}, Oid = {NLM: PMC221249}, Oto = {NLM}, Own = {NLM}, Pages = {703--710}, Pl = {UNITED STATES}, Pmc = {PMC221249}, pmid = {14077501}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {OM}, Status = {MEDLINE}, Title = {Chemoaffinity in the orderly growth of nerve fiber patterns and connections}, Volume = {50}, Year = {1963}, url = {papers/Sperry_ProcNatlAcadSciUSA1963.pdf}} @article{Holt:1983, Abstract = {Retinal nerve fibres form an orderly map of visual space in several centres in the vertebrate brain. Such topographic maps are a common feature of central nervous system organization, yet the way in which they develop is poorly understood. Early nerve projections in the fetal and neonatal mammalian brain have been found in several cases to be less restricted than those in the adult, suggesting that nerve fibres may initially form a diffuse set of connections in their target structure from which the adult map is sculpted by the elimination of terminals. Indeed, previous electrophysiological data indicate that the retinotectal map in Xenopus laevis might be initially disorganized. We report here, however, that the retinotectal projection is ordered from the beginning of tectal innervation (stage 39/40). We demonstrate this first autoradiographically by tracing groups of growing ganglion cell axons which we labelled by incubating sectors of eye rudiments, before axonal outgrowth, in 3H-proline and replacing them orthotopically. Separate labelling of dorsal and ventral parts of the initial projection showed that retinal fibres are organized topographically, as in the adult, in the tectal rudiment and throughout much of the pathway. Second, we show that visual responses are ordered in the tectum from the first stage that they can be mapped (stage 40). We conclude that the topographic ordering of retinotectal connections develops as a result of directed axonal outgrowth.}, Author = {Holt, C E and Harris, W A}, Crdt = {1983/01/13 00:00}, Da = {19830317}, Date = {1983 Jan 13}, Date-Added = {2009-03-26 17:58:21 -0400}, Date-Modified = {2013-08-27 20:03:45 +0000}, Dcom = {19830317}, Edat = {1983/01/13}, Gr = {HD14490-01/HD/NICHD NIH HHS/United States}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {spontaneous activity; activity-development; visual system; optic tectum; Xenopus; frog; Retina; currOpinRvw}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Axons/ultrastructure; Nerve Fibers/*ultrastructure; Photic Stimulation; Retina/*growth \& development; Tectum Mesencephali/*growth \& development/ultrastructure; Visual Fields; Xenopus laevis}, Mhda = {1983/01/13 00:01}, Month = {Jan}, Number = {5896}, Own = {NLM}, Pages = {150--152}, Pl = {ENGLAND}, pmid = {6823290}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Order in the initial retinotectal map in Xenopus: a new technique for labelling growing nerve fibres}, Volume = {301}, Year = {1983}, url = {papers/Holt_Nature1983.pdf}} @article{Stryker:1986, Abstract = {Ocular dominance columns in the cat's visual cortex appear to develop out of an initially overlapping projection by a progressive segregation of the geniculocortical afferents serving the 2 eyes (reviewed in LeVay and Stryker, 1979). To determine whether electrical activity in the visual afferent pathway is involved in this normal, developmental rearrangement of synaptic connections, we blocked the discharge of retinal ganglion cells in both eyes by making repeated intravitreal injections of tetrodotoxin (TTX) during the period in which geniculocortical afferent segregation would normally be taking place. Control experiments for the side effects of the injection procedure, the systemic effects of TTX, and the effects of visual deprivation were carried out, and a series of normal animals of appropriate ages was also studied. We then examined the effects of retinal blockade and the various control procedures on the formation of ocular dominance columns using an anatomical assay, the autoradiographic labeling of geniculocortical afferent terminals in layer IV of the visual cortex by the transneuronal transport of tritiated proline injected into 1 eye, and a physiological assay, the ocular dominance of single cortical cells recorded extracellularly. After retinal TTX blockade, layer IV was labeled uniformly without periodic fluctuation in grain density, and nearly all cortical cells were driven well through both eyes. These assays thus indicated that retinal blockade completely blocked the formation of ocular dominance columns, unlike any of the control procedures, suggesting that the spontaneous maintained discharge of retinal ganglion cells may have an important role in the normal development of binocular connections in the visual cortex.}, Author = {Stryker, M P and Harris, W A}, Crdt = {1986/08/01 00:00}, Da = {19861002}, Date = {1986 Aug}, Date-Added = {2009-03-26 15:34:10 -0400}, Date-Modified = {2013-08-27 20:26:54 +0000}, Dcom = {19861002}, Edat = {1986/08/01}, Gr = {K04-EY00213/EY/NEI NIH HHS/United States; R01-EY-02874/EY/NEI NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology; currOpinRvw}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Cats; Darkness; Evoked Potentials, Visual; *Functional Laterality; Histocytochemistry; Mathematics; *Photic Stimulation; Retinal Ganglion Cells/physiology; Tetrodotoxin; Visual Cortex/growth \& development/*physiology}, Mhda = {1986/08/01 00:01}, Month = {Aug}, Number = {8}, Own = {NLM}, Pages = {2117--2133}, Pl = {UNITED STATES}, pmid = {3746403}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Status = {MEDLINE}, Title = {Binocular impulse blockade prevents the formation of ocular dominance columns in cat visual cortex}, Volume = {6}, Year = {1986}, url = {papers/Stryker_JNeurosci1986.pdf}} @article{Bestman:2008, Abstract = {Visual system development requires experience-dependent mechanisms that regulate neuronal structure and function, including dendritic arbor growth, synapse formation, and stabilization. Although RNA binding proteins have been shown to affect some forms of synaptic plasticity in adult animals, their role in the development of neuronal structure and functional circuitry is not clear. Using two-photon time-lapse in vivo imaging and electrophysiology combined with morpholino-mediated knockdown and expression of functional deletion mutants, we demonstrate that the mRNA binding protein, cytoplasmic polyadenylation element binding protein1 (CPEB1), affects experience-dependent neuronal development and circuit formation in the visual system of Xenopus laevis. These data indicate that sensory experience controls circuit development by regulating translational activity of mRNAs.}, Address = {Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.}, Author = {Bestman, Jennifer E and Cline, Hollis T}, Crdt = {2008/12/17 09:00}, Da = {20081224}, Date = {2008 Dec 23}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20090127}, Dep = {20081212}, Edat = {2008/12/17 09:00}, Issn = {1091-6490 (Electronic)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20090204}, Mh = {Animals; Dendrites/*ultrastructure; *Morphogenesis; Mutation; *Neurogenesis; Neuronal Plasticity/physiology; Ocular Physiological Phenomena; Polyadenylation; Protein Biosynthesis; RNA, Messenger; RNA, Small Interfering/pharmacology; RNA-Binding Proteins/*physiology; Transcription Factors/*physiology; Xenopus Proteins/*physiology; Xenopus laevis/physiology; mRNA Cleavage and Polyadenylation Factors/*physiology}, Mhda = {2009/01/28 09:00}, Month = {Dec}, Number = {51}, Oid = {NLM: PMC2629308 {$[$}Available on 06/23/09{$]$}}, Own = {NLM}, Pages = {20494--20499}, Phst = {2008/12/12 {$[$}aheadofprint{$]$}}, Pii = {0806296105}, Pl = {United States}, Pmc = {PMC2629308}, Pmcr = {2009/06/23}, pmid = {19074264}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Cpeb1 protein, Xenopus); 0 (RNA, Messenger); 0 (RNA, Small Interfering); 0 (RNA-Binding Proteins); 0 (Transcription Factors); 0 (Xenopus Proteins); 0 (mRNA Cleavage and Polyadenylation Factors)}, Sb = {IM}, Source = {Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20494-9. Epub 2008 Dec 12.}, Status = {MEDLINE}, Title = {The RNA binding protein CPEB regulates dendrite morphogenesis and neuronal circuit assembly in vivo}, Volume = {105}, Year = {2008}, url = {papers/Bestman_ProcNatlAcadSciUSA2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0806296105}} @article{Lee:2008a, Abstract = {The contribution of structural remodeling to long-term adult brain plasticity is unclear. Here, we investigate features of GABAergic interneuron dendrite dynamics and extract clues regarding its potential role in cortical function and circuit plasticity. We show that remodeling interneurons are contained within a "dynamic zone" corresponding to a superficial strip of layers 2/3, and remodeling dendrites respect the lower border of this zone. Remodeling occurs primarily at the periphery of dendritic fields with addition and retraction of new branch tips. We further show that dendrite remodeling is not intrinsic to a specific interneuron class. These data suggest that interneuron remodeling is not a feature predetermined by genetic lineage, but rather, it is imposed by cortical laminar circuitry. Our findings are consistent with dynamic GABAergic modulation of feedforward and recurrent connections in response to top-down feedback and suggest a structural component to functional plasticity of supragranular neocortical laminae.}, Address = {The Picower Institute for Learning and Memory and Departments of Brain and Cognitive Sciences, Biology, and Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, Author = {Lee, Wei-Chung Allen and Chen, Jerry L and Huang, Hayden and Leslie, Jennifer H and Amitai, Yael and So, Peter T and Nedivi, Elly}, Crdt = {2008/12/11 09:00}, Da = {20081217}, Date = {2008 Dec 16}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20090112}, Dep = {20081209}, Edat = {2008/12/11 09:00}, Gr = {R01 EY017656/EY/NEI NIH HHS/United States; R03 EY014891/EY/NEI NIH HHS/United States; R21 EB004646/EB/NIBIB NIH HHS/United States}, Issn = {1091-6490 (Electronic)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {21 Neurophysiology; 10 Structural plasticity}, Language = {eng}, Lr = {20090126}, Mh = {Animals; Interneurons/*physiology/ultrastructure; Mice; Mice, Transgenic; Neocortex/*physiology/ultrastructure; *Neuronal Plasticity; gamma-Aminobutyric Acid/metabolism}, Mhda = {2009/01/13 09:00}, Month = {Dec}, Number = {50}, Oid = {NLM: PMC2604980 {$[$}Available on 06/16/09{$]$}}, Own = {NLM}, Pages = {19968--19973}, Phst = {2008/12/09 {$[$}aheadofprint{$]$}}, Pii = {0810149105}, Pl = {United States}, Pmc = {PMC2604980}, Pmcr = {2009/06/16}, pmid = {19066223}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Rn = {56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Source = {Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19968-73. Epub 2008 Dec 9.}, Status = {MEDLINE}, Title = {A dynamic zone defines interneuron remodeling in the adult neocortex}, Volume = {105}, Year = {2008}, url = {papers/Lee_ProcNatlAcadSciUSA2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0810149105}} @article{Tomura:2008, Abstract = {Kaede is a photoconvertible fluorescence protein that changes from green to red upon exposure to violet light. The photoconversion of intracellular Kaede has no effect on cellular function. Using transgenic mice expressing the Kaede protein, we demonstrated that movement of cells with the photoconverted Kaede protein could be monitored from lymphoid organs to other tissues as well as from skin to the draining lymph node. Analysis of the kinetics of cellular movement revealed that each subset of cells in the lymph node, such as CD4(+) T, CD8(+) T, B, and dendritic cells, has a distinct migration pattern in vivo. Thus, the Kaede transgenic mouse system would be an ideal tool to monitor precise cellular movement in vivo at different stages of immune response to pathogens as well as in autoimmune diseases.}, Address = {Laboratory for Autoimmune Regulation, Research Center for Allergy and Immunology, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama City, Kanagawa 230-0045, Japan.}, Author = {Tomura, Michio and Yoshida, Naoki and Tanaka, Junko and Karasawa, Satoshi and Miwa, Yoshihiro and Miyawaki, Atsushi and Kanagawa, Osami}, Crdt = {2008/07/30 09:00}, Da = {20080806}, Date = {2008 Aug 5}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080925}, Dep = {20080728}, Edat = {2008/07/30 09:00}, Issn = {1091-6490 (Electronic)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {23 Technique}, Language = {eng}, Lr = {20090206}, Mh = {Animals; Cell Movement/*immunology; Flow Cytometry; Fluorescent Antibody Technique; Hela Cells; Humans; Immune System/*cytology; Luminescent Proteins/*metabolism; Mice; Mice, Transgenic}, Mhda = {2008/09/26 09:00}, Month = {Aug}, Number = {31}, Oid = {NLM: PMC2504797}, Own = {NLM}, Pages = {10871--10876}, Phst = {2008/07/28 {$[$}aheadofprint{$]$}}, Pii = {0802278105}, Pl = {United States}, Pmc = {PMC2504797}, pmid = {18663225}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article}, Rn = {0 (Kaede protein, Trachyphyllia geoffroyi); 0 (Luminescent Proteins)}, Sb = {IM}, Source = {Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10871-6. Epub 2008 Jul 28.}, Status = {MEDLINE}, Title = {Monitoring cellular movement in vivo with photoconvertible fluorescence protein "Kaede" transgenic mice}, Volume = {105}, Year = {2008}, url = {papers/Tomura_ProcNatlAcadSciUSA2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0802278105}} @article{Huberman:2008a, Abstract = {Patterns of synaptic connections in the visual system are remarkably precise. These connections dictate the receptive field properties of individual visual neurons and ultimately determine the quality of visual perception. Spontaneous neural activity is necessary for the development of various receptive field properties and visual feature maps. In recent years, attention has shifted to understanding the mechanisms by which spontaneous activity in the developing retina, lateral geniculate nucleus, and visual cortex instruct the axonal and dendritic refinements that give rise to orderly connections in the visual system. Axon guidance cues and a growing list of other molecules, including immune system factors, have also recently been implicated in visual circuit wiring. A major goal now is to determine how these molecules cooperate with spontaneous and visually evoked activity to give rise to the circuits underlying precise receptive field tuning and orderly visual maps.}, Address = {Department of Neurobiology, Stanford University School of Medicine, Palo Alto, California 94305, USA. adh1@stanford.edu}, Author = {Huberman, Andrew D and Feller, Marla B and Chapman, Barbara}, Crdt = {2008/06/19 09:00}, Da = {20080618}, Date = {2008}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2013-05-31 20:00:30 +0000}, Dcom = {20080919}, Edat = {2008/06/19 09:00}, Gr = {EY11369/EY/NEI NIH HHS/United States; R01 EY011369-11/EY/NEI NIH HHS/United States; R01 EY13528/EY/NEI NIH HHS/United States}, Issn = {0147-006X (Print)}, Jid = {7804039}, Journal = {Annu Rev Neurosci}, Jt = {Annual review of neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal wave paper;Spontaneous activity;frontiers review;visual cortex;visual system;LGN;Superior Colliculus;optic tectum;Retina;plasticity;experience dependent plasticity;structural remodeling;review; currOpinRvw}, Language = {eng}, Lr = {20090316}, Mh = {Animals; Brain Mapping; Cell Differentiation/physiology; Growth Cones/*physiology/ultrastructure; Humans; Nerve Growth Factors/metabolism/secretion; Retina/embryology/*physiology; Synapses/physiology/ultrastructure; Visual Cortex/embryology/*physiology; Visual Fields/physiology; Visual Pathways/embryology/*physiology}, Mhda = {2008/09/20 09:00}, Mid = {NIHMS80268}, Oid = {NLM: NIHMS80268; NLM: PMC2655105}, Own = {NLM}, Pages = {479--509}, Pl = {United States}, Pmc = {PMC2655105}, pmid = {18558864}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review}, Rf = {200}, Rn = {0 (Nerve Growth Factors)}, Sb = {IM}, Source = {Annu Rev Neurosci. 2008;31:479-509.}, Status = {MEDLINE}, Title = {Mechanisms underlying development of visual maps and receptive fields}, Volume = {31}, Year = {2008}, url = {papers/Huberman_AnnuRevNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.31.060407.125533}} @article{Hudetz:2007, Abstract = {BACKGROUND: The degree of suppression of sensory functions during general anesthesia is controversial. Here, the authors investigated whether discrete flash stimuli induced cortical field potential responses at an isoflurane concentration producing burst suppression and compared the spatiotemporal properties and frequency spectra of flash-induced burst responses with those occurring spontaneously. METHODS: Rats were equipped with multiple epidural and intracortical electrodes to record cortical field potentials in the right hemisphere at several locations along the anterior-posterior axis. At isoflurane concentrations of 1.1, 1.4, and 1.8%, discrete light flashes were delivered to the left eye while cortical field potentials were continuously recorded. RESULTS: Isoflurane at 1.4-1.8% produced burst suppression. Each flash produced a visual evoked potential in the primary visual cortex followed by secondary bursting activity in more anterior regions. The average latency and duration of these bursts were 220 and 810 ms, respectively. The spontaneous and flash-induced bursts were similar in frequency, duration, and spatial distribution. They had maximum power in the frontal (primary motor) cortex with a dominant frequency of 10 Hz. CONCLUSIONS: The results suggest that discrete flash stimuli activate the motor regions of the cerebral cortex during isoflurane anesthesia and that these activations are analogous with those that occur spontaneously during burst suppression. Electrocortical suppression of the cortex during anesthesia does not prevent its response to visual stimuli.}, Address = {Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, Wisconsin 53226, USA. ahudetz@mcw.edu}, Author = {Hudetz, Anthony G and Imas, Olga A}, Crdt = {2007/11/29 09:00}, Da = {20071128}, Date = {2007 Dec}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20071220}, Edat = {2007/11/29 09:00}, Gr = {R01 GM-56398/GM/NIGMS NIH HHS/United States}, Issn = {1528-1175 (Electronic)}, Jid = {1300217}, Journal = {Anesthesiology}, Jt = {Anesthesiology}, Keywords = {21 Neurophysiology}, Language = {eng}, Mh = {Action Potentials/drug effects/*physiology; *Anesthesia, Inhalation/methods; Animals; Cerebral Cortex/drug effects/physiology; Isoflurane/*pharmacology; Male; Photic Stimulation/*methods; Rats; Rats, Sprague-Dawley}, Mhda = {2007/12/21 09:00}, Month = {Dec}, Number = {6}, Own = {NLM}, Pages = {983--991}, Pii = {00000542-200712000-00018}, Pl = {United States}, pmid = {18043067}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural}, Rn = {26675-46-7 (Isoflurane)}, Sb = {AIM; IM}, Source = {Anesthesiology. 2007 Dec;107(6):983-91.}, Status = {MEDLINE}, Title = {Burst activation of the cerebral cortex by flash stimuli during isoflurane anesthesia in rats}, Volume = {107}, Year = {2007}, url = {papers/Hudetz_Anesthesiology2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1097/01.anes.0000291471.80659.55}} @article{Cline:2003, Abstract = {The interface between so-called activity-dependent and activity-independent mechanisms of circuit development is discussed here in light of recent findings that question the role of activity in brain development. This debate is presented simplistically here in terms of Sperry's chemoaffinity hypothesis versus Hebb's rules of correlation-based synaptic change, which are often presented as being mutually exclusive - much like oil and vinegar.}, Address = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.}, Author = {Cline, Hollis}, Crdt = {2003/11/20 05:00}, Da = {20031119}, Date = {2003 Dec}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2009-03-26 15:30:46 -0400}, Dcom = {20040128}, Edat = {2003/11/20 05:00}, Issn = {0166-2236 (Print)}, Jid = {7808616}, Journal = {Trends Neurosci}, Jt = {Trends in neurosciences}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20051116}, Mh = {Animals; Brain/*growth \& development/metabolism; Gene Expression Regulation, Developmental/*physiology; Humans; Nerve Net/*growth \& development/metabolism; Synapses/genetics/*physiology}, Mhda = {2004/01/30 05:00}, Month = {Dec}, Number = {12}, Own = {NLM}, Pages = {655--661}, Pii = {S0166223603003412}, Pl = {England}, pmid = {14624849}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {52}, Sb = {IM}, Source = {Trends Neurosci. 2003 Dec;26(12):655-61.}, Status = {MEDLINE}, Title = {Sperry and Hebb: oil and vinegar?}, Volume = {26}, Year = {2003}, url = {papers/Cline_TrendsNeurosci2003.pdf}} @article{Chisum:2003, Abstract = {The superficial layers of primary visual cortex, unlike layer 4, have an extensive network of long-range horizontal connections linking sites of similar orientation preference. To identify possible functional consequences of this distinct anatomy, we compared the receptive field properties of layers 2/3 and 4 neurons in tree shrew primary visual cortex with electrophysiological recordings. We found that elongated receptive fields, strong orientation tuning, and length summation (properties predicted by the anatomy of the horizontal connections) are present in layer 2/3 neurons, but not in layer 4 neurons. We further characterized the summation fields of layer 2/3 neurons and found axis and orientation-specific facilitation that matched the distribution of horizontal connections. The functional signature of horizontal connections was also evident in the population response of layer 2/3 neurons; the intrinsic signal activation pattern elicited by an array of collinear Gabor elements was significantly stronger than that elicited by a noncollinear array. Furthermore, our results showed that this enhancement of population response was achieved without compromising spatial resolution along the collinear axis, providing stimulus-specific facilitation without filling in between stimuli. Taken together, these results suggest that horizontal connections play a significant role in shaping the visual responses of layer 2/3 neurons.}, Address = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. hchisum@neuro.duke.edu}, Author = {Chisum, Heather J and Mooser, Francois and Fitzpatrick, David}, Crdt = {2003/04/10 05:00}, Da = {20030409}, Date = {2003 Apr 1}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2009-03-26 15:28:52 -0400}, Dcom = {20030530}, Edat = {2003/04/10 05:00}, Gr = {EY06821/EY/NEI NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Electrophysiology; Female; Male; Neurons/cytology/*physiology; Photic Stimulation; Tupaiidae; Visual Cortex/*cytology; Visual Fields; Visual Pathways}, Mhda = {2003/05/31 05:00}, Month = {Apr}, Number = {7}, Own = {NLM}, Pages = {2947--2960}, Pii = {23/7/2947}, Pl = {United States}, pmid = {12684482}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {J Neurosci. 2003 Apr 1;23(7):2947-60.}, Status = {MEDLINE}, Title = {Emergent properties of layer 2/3 neurons reflect the collinear arrangement of horizontal connections in tree shrew visual cortex}, Volume = {23}, Year = {2003}, url = {papers/Chisum_JNeurosci2003.pdf}} @article{Maskos:2002, Abstract = {The function of the nervous system is a consequence of the intricate synaptic connectivity of its neurons. Our understanding of these highly complex networks has profited enormously from methods used over the past two decades that are based on the mechanical injection of tracer molecules into brain regions. We have developed a genetic system for the mapping of synaptic connections during development of the mammalian central nervous system and in the mature brain. It is based on the transsynaptic transfer of green fluorescent protein (GFP) in the brains of mice using a fusion protein with a nontoxic fragment of tetanus toxin (TTC) expressed in defined neurons. These transgenic mice allowed us to visualize neurons, at single-cell resolution, that are in synaptic contact by the detection of GFP in interconnected circuits. Targeted genetic expression with a specific promoter permitted us to transfer GFP to defined subsets of neurons and brain regions. GFP-TTC is coexpressed with a lacZ reporter gene to discriminate neurons that produce the tracer from cells that have acquired it transneuronally. The marker shows selective transfer in the retrograde direction. We have used electron microscopic detection of GFP to define the ultrastructural features of the system. Our work opens up a range of possibilities for brain slice and in vivo studies taking advantage of the fluorescence of GFP. We point the way toward the use of powerful multiphoton technology and set the stage for the transsynaptic transfer of other proteins in the brains of mice.}, Address = {Unite d'Embryologie Moleculaire, Unite de Recherche Associee 1947, Centre National de la Recherche Scientifique, Institut Pasteur, F-75724 Paris Cedex 15, France.}, Author = {Maskos, Uwe and Kissa, Karima and St Cloment, Cecile and Brulet, Philippe}, Crdt = {2002/07/13 10:00}, Da = {20020724}, Date = {2002 Jul 23}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20020904}, Dep = {20020711}, Edat = {2002/07/13 10:00}, Issn = {0027-8424 (Print)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Keywords = {23 Technique}, Language = {eng}, Lr = {20081120}, Mh = {Animals; Base Sequence; *Chromosome Mapping; DNA Primers; Genes, Reporter; Green Fluorescent Proteins; In Situ Hybridization; Luminescent Proteins/*genetics/metabolism; Mice; Mice, Transgenic; Molecular Sequence Data; Neurons/*physiology; Polymerase Chain Reaction; Protein Transport; Recombinant Fusion Proteins/metabolism; Reproducibility of Results; Synapses/*physiology; beta-Galactosidase/genetics/metabolism}, Mhda = {2002/09/06 10:01}, Month = {Jul}, Number = {15}, Oid = {NLM: PMC126634}, Own = {NLM}, Pages = {10120--10125}, Phst = {2002/07/11 {$[$}aheadofprint{$]$}}, Pii = {152266799}, Pl = {United States}, Pmc = {PMC126634}, pmid = {12114537}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (DNA Primers); 0 (Luminescent Proteins); 0 (Recombinant Fusion Proteins); 147336-22-9 (Green Fluorescent Proteins); EC 3.2.1.23 (beta-Galactosidase)}, Sb = {IM}, Source = {Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):10120-5. Epub 2002 Jul 11.}, Status = {MEDLINE}, Title = {Retrograde trans-synaptic transfer of green fluorescent protein allows the genetic mapping of neuronal circuits in transgenic mice}, Volume = {99}, Year = {2002}, url = {papers/Maskos_ProcNatlAcadSciUSA2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.152266799}} @article{Tan:2002, Abstract = {The mammalian superior colliculus is structurally and functionally divided into two entities: superficial visual and deep multimodal motor. To discover the role, if any, of developmental processes in establishing separate tectal compartments, we have used highly unbalanced mouse chimaeras to mark cell dispersion pathways and trace cell lineages. Two forms of cell dispersion were detected: radial and tangential. Neither radial nor tangential forms of cell dispersion were found to exist on their own in any group of labeled cells. Radial cell dispersion was the predominant form of cell movement from the germinal zones and primarily associated with the differentiation of glutamatergic neurons. In contrast, tangential cell dispersion involved a minority of tectal cells, concentrated chiefly in the superficial layers and often associated with the upper aspects of radial columns. More scattered cells expressed gamma-aminobutyric acid (GABA) compared to columnar cells. Taken together, these results indicate separate developmental constraints for the development of glutamatergic and GABAergic neurons in the superior colliculus.}, Address = {Brain Development Group, Howard Florey Institute, Parkville, Victoria, Australia. stan@hfi.unimel.edu.au}, Author = {Tan, Seong-Seng and Valcanis, Helen and Kalloniatis, Michael and Harvey, Alan}, Crdt = {2002/01/11 10:00}, Da = {20020110}, Date = {2002 Jan 1}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20020211}, Edat = {2002/01/11 10:00}, Issn = {0012-1606 (Print)}, Jid = {0372762}, Journal = {Dev Biol}, Jt = {Developmental biology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Body Patterning; Cell Movement; Chimera; Glutamic Acid/metabolism; Immunohistochemistry; Lac Operon; Mice; Mice, Transgenic; Neurons/cytology/metabolism; Phenotype; Superior Colliculi/cytology/*embryology/*growth \& development/metabolism; gamma-Aminobutyric Acid/metabolism}, Mhda = {2002/02/12 10:01}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {117--131}, Pii = {S0012160601905056}, Pl = {United States}, pmid = {11784099}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {56-12-2 (gamma-Aminobutyric Acid); 56-86-0 (Glutamic Acid)}, Sb = {IM}, Source = {Dev Biol. 2002 Jan 1;241(1):117-31.}, Status = {MEDLINE}, Title = {Cellular dispersion patterns and phenotypes in the developing mouse superior colliculus}, Volume = {241}, Year = {2002}, url = {papers/Tan_DevBiol2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/dbio.2001.0505}} @article{Klier:2001, Abstract = {The superior colliculus (SC) has a topographic map of visual space, but the spatial nature of its output command for orienting gaze shifts remains unclear. Here we show that the SC codes neither desired gaze displacement nor gaze direction in space (as debated previously), but rather, desired gaze direction in retinal coordinates. Electrical micro-stimulation of the SC in two head-free (non-immobilized) monkeys evoked natural-looking, eye-head gaze shifts, with anterior sites producing small, fixed-vector movements and posterior sites producing larger, strongly converging movements. However, when correctly calculated in retinal coordinates, all of these trajectories became 'fixed-vector.' Moreover, our data show that this eye-centered SC command is then further transformed, as a function of eye and head position, by downstream mechanisms into the head- and body-centered commands for coordinated eye-head gaze shifts.}, Address = {CIHR Group for Action and Perception, York University, 4700 Keele Street, Toronto, Ontario M3J 1P3, Canada.}, Author = {Klier, E M and Wang, H and Crawford, J D}, Crdt = {2001/05/23 10:00}, Da = {20010522}, Date = {2001 Jun}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20010705}, Edat = {2001/05/23 10:00}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Darkness; Fixation, Ocular/*physiology; Head Movements/*physiology; Light; Macaca fascicularis; Mesencephalon/physiology; Motor Activity; Neurons/*physiology; Photic Stimulation; Retina/*physiology; Saccades/*physiology; Superior Colliculi/*physiology}, Mhda = {2001/07/06 10:01}, Month = {Jun}, Number = {6}, Own = {NLM}, Pages = {627--632}, Pii = {88450}, Pl = {United States}, pmid = {11369944}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {Nat Neurosci. 2001 Jun;4(6):627-32.}, Status = {MEDLINE}, Title = {The superior colliculus encodes gaze commands in retinal coordinates}, Volume = {4}, Year = {2001}, url = {papers/Klier_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/88450}} @article{Branner:2001, Abstract = {Restoration of motor function to individuals who have had spinal cord injuries or stroke has been hampered by the lack of an interface to the peripheral nervous system. A suitable interface should provide selective stimulation of a large number of individual muscle groups with graded recruitment of force. We have developed a new neural interface, the Utah Slanted Electrode Array (USEA), that was designed to be implanted into peripheral nerves. Its goal is to provide such an interface that could be useful in rehabilitation as well as neuroscience applications. In this study, the stimulation capabilities of the USEA were evaluated in acute experiments in cat sciatic nerve. The recruitment properties and the selectivity of stimulation were examined by determining the target muscles excited by stimulation via each of the 100 electrodes in the array and using force transducers to record the force produced in these muscles. It is shown in the results that groups of up to 15 electrodes were inserted into individual fascicles. Stimulation slightly above threshold was selective to one muscle group for most individual electrodes. At higher currents, co-activation of agonist but not antagonist muscles was observed in some instances. Recruitment curves for the electrode array were broader with twitch thresholds starting at much lower currents than for cuff electrodes. In these experiments, it is also shown that certain combinations of electrode pairs, inserted into an individual fascicle, excite fiber populations with substantial overlap, whereas other pairs appear to address independent populations. We conclude that the USEA permits more selective stimulation at much lower current intensities with more graded recruitment of individual muscles than is achieved by conventional cuff electrodes.}, Address = {The Center for Neural Interfaces, Department of Bioengineering, University of Utah, Salt Lake City, Utah 84112, USA.}, Author = {Branner, A and Stein, R B and Normann, R A}, Crdt = {2001/04/05 10:00}, Da = {20010405}, Date = {2001 Apr}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2009-03-26 15:28:52 -0400}, Dcom = {20010705}, Edat = {2001/04/05 10:00}, Gr = {1-R01-NS-39677/NS/NINDS NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Cats; Computer Simulation; Electric Stimulation/*instrumentation/*methods; Equipment Design; Microelectrodes; Models, Biological; Muscle Contraction; Muscle, Skeletal/physiology; Recruitment, Neurophysiological/physiology; Sciatic Nerve/*physiology}, Mhda = {2001/07/11 10:01}, Month = {Apr}, Number = {4}, Own = {NLM}, Pages = {1585--1594}, Pl = {United States}, pmid = {11287482}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {J Neurophysiol. 2001 Apr;85(4):1585-94.}, Status = {MEDLINE}, Title = {Selective stimulation of cat sciatic nerve using an array of varying-length microelectrodes}, Volume = {85}, Year = {2001}, url = {papers/Branner_JNeurophysiol2001.pdf}} @article{Wickelgren:2000, Abstract = {For decades, neurobiologists have believed that so-called ocular dominance columns--neat columns of brain cells that respond to visual activity from one eye or the other--form as a result of visual activity. Now, in work described on page 1321, neuroscientists report that ocular dominance columns in ferrets appear long before the columns can be modified by visual experience. They propose instead that innate molecules that guide growing axons to their locations in the developing brain may be primarily responsible for building these columns. But others contest the conclusion that neural activity is not required for constructing the columns, arguing that there are other explanations for the researchers' findings.}, Author = {Wickelgren, I}, Con = {Science. 2000 Nov 17;290(5495):1321-4. PMID: 11082053}, Crdt = {2001/02/24 12:00}, Da = {20001120}, Date = {2000 Nov 17}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2009-03-26 15:30:46 -0400}, Dcom = {20001207}, Edat = {2001/02/24 12:00}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20070817}, Mh = {Animals; Animals, Newborn; Axons/physiology; Ferrets; Geniculate Bodies/physiology; Photic Stimulation; Retina/physiology; Sensory Deprivation; Time Factors; Visual Cortex/cytology/*growth \& development/*physiology; Visual Pathways/growth \& development/*physiology; *Visual Perception}, Mhda = {2001/02/28 10:01}, Month = {Nov}, Number = {5495}, Own = {NLM}, Pages = {1271--1273}, Pl = {UNITED STATES}, pmid = {11185393}, Pst = {ppublish}, Pt = {Comment; News}, Sb = {IM}, Source = {Science. 2000 Nov 17;290(5495):1271-3.}, Status = {MEDLINE}, Title = {Neurobiology. Heretical view of visual development}, Volume = {290}, Year = {2000}} @article{Crowley:2000, Abstract = {The segregation of lateral geniculate nucleus (LGN) axons into ocular dominance columns is believed to involve a prolonged, activity-dependent sorting process. However, visualization of early postnatal ferret LGN axons by direct LGN tracer injections revealed segregated ocular dominance columns <7 days after innervation of layer 4. These early columns were unaffected by experimentally induced imbalances in retinal activity, implying that different mechanisms govern initial column formation and their modification during the subsequent critical period. Instead of activity-dependent plasticity, we propose that ocular dominance column formation relies on the targeting of distinct axonal populations to defined locales in cortical layer 4.}, Address = {Howard Hughes Medical Institute and Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. jcrowley@neuro.duke.edu}, Author = {Crowley, J C and Katz, L C}, Cin = {Science. 2000 Nov 17;290(5495):1271-3. PMID: 11185393}, Crdt = {2000/11/18 11:00}, Da = {20001120}, Date = {2000 Nov 17}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2013-08-27 20:02:41 +0000}, Dcom = {20001207}, Edat = {2000/11/18 11:00}, Gr = {EY07690/EY/NEI NIH HHS/United States; MH12359/MH/NIMH NIH HHS/United States}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology; 21 Activity-development; currOpinRvw}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Animals, Newborn; Axons/*physiology; Female; Ferrets; Geniculate Bodies/cytology/*physiology; Male; Neurons, Afferent/physiology; Photic Stimulation; Retina/physiology; Sensory Deprivation; Vision, Ocular; Visual Cortex/cytology/*growth \& development/physiology; Visual Pathways/growth \& development/*physiology; *Visual Perception}, Mhda = {2001/02/28 10:01}, Month = {Nov}, Number = {5495}, Own = {NLM}, Pages = {1321--1324}, Pii = {8992}, Pl = {UNITED STATES}, pmid = {11082053}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Science. 2000 Nov 17;290(5495):1321-4.}, Status = {MEDLINE}, Title = {Early development of ocular dominance columns}, Volume = {290}, Year = {2000}, url = {papers/Crowley_Science2000.pdf}} @article{Jones:2000, Abstract = {After manipulations of the periphery that reduce or enhance input to the somatosensory cortex, affected parts of the body representation will contract or expand, often over many millimeters. Various mechanisms, including divergence of preexisting connections, expression of latent synapses, and sprouting of new synapses, have been proposed to explain such phenomena, which probably underlie altered sensory experiences associated with limb amputation and peripheral nerve injury in humans. Putative cortical mechanisms have received the greatest emphasis but there is increasing evidence for substantial reorganization in subcortical structures, including the brainstem and thalamus, that may be of sufficient extent to account for or play a large part in representational plasticity in somatosensory cortex. Recent studies show that divergence of ascending connections is considerable and sufficient to ensure that small alterations in map topography at brainstem and thalamic levels will be amplified in the projection to the cortex. In the long term, slow, deafferentation-dependent transneuronal atrophy at brainstem, thalamic, and even cortical levels are operational in promoting reorganizational changes, and the extent to which surviving connections can maintain a map is a key to understanding differences between central and peripheral deafferentation.}, Address = {Center for Neuroscience, University of California, Davis 95616, USA. ejones@ucdavis.edu}, Author = {Jones, E G}, Crdt = {2000/06/09 09:00}, Da = {20000908}, Date = {2000}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20000908}, Edat = {2000/06/09 09:00}, Gr = {NS21377/NS/NINDS NIH HHS/United States}, Issn = {0147-006X (Print)}, Jid = {7804039}, Journal = {Annu Rev Neurosci}, Jt = {Annual review of neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071114}, Mh = {Afferent Pathways/physiology; Animals; Cerebral Cortex/*physiology; Neuronal Plasticity/*physiology; Peripheral Nerves/physiology; Primates/*physiology; Somatosensory Cortex/*physiology; Spinal Cord/physiology; Thalamus/physiology; gamma-Aminobutyric Acid/physiology}, Mhda = {2000/09/19 11:01}, Own = {NLM}, Pages = {1--37}, Pl = {UNITED STATES}, pmid = {10845057}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {182}, Rn = {56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Source = {Annu Rev Neurosci. 2000;23:1-37.}, Status = {MEDLINE}, Title = {Cortical and subcortical contributions to activity-dependent plasticity in primate somatosensory cortex}, Volume = {23}, Year = {2000}, url = {papers/Jones_AnnuRevNeurosci2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.23.1.1}} @article{Crowley:1999, Abstract = {The initial establishment of ocular dominance columns in visual cortex is believed to involve the segregation of overlapping geniculocortical axons into eye-specific patches based on patterns of correlated activity. However, we found that total removal of retinal influence early in visual development did not prevent segregation of geniculocortical axons into alternating stripes with periodicity normal for ocular dominance columns. Because the patterning of geniculocortical afferents resists this dramatic change in the level, source and pattern of spontaneous activity, we propose that formation of ocular dominance columns relies on molecular cues present on thalamic axons, cortical cells or both.}, Address = {Howard Hughes Medical Institute and Department of Neurobiology, Box 3209, Duke University Medical Center, Durham, North Carolina 27710, USA. jcrowley@neuro.duke.edu}, Author = {Crowley, J C and Katz, L C}, Cin = {Nat Neurosci. 1999 Dec;2(12):1043-5. PMID: 10570475}, Crdt = {1999/11/26 09:00}, Da = {20000118}, Date = {1999 Dec}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20000118}, Edat = {1999/11/26 09:00}, Gr = {EYO7960/EY/NEI NIH HHS/United States; MH12359/MH/NIMH NIH HHS/United States}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081121}, Mh = {Aging; Animals; Animals, Newborn; Axons/physiology; Biotin/analogs \& derivatives/metabolism; Dextrans/metabolism; Female; Ferrets; Fluorescent Dyes/metabolism; Geniculate Bodies/cytology/growth \& development/physiology; Male; Microspheres; Neurons, Afferent/physiology; Retina/*physiology/surgery; Sensory Deprivation/*physiology; Time Factors; Vision, Ocular/*physiology; Visual Cortex/cytology/drug effects/*growth \& development/*physiology; Visual Pathways/*growth \& development/physiology; Visual Perception/physiology}, Mhda = {2001/03/23 10:01}, Month = {Dec}, Number = {12}, Own = {NLM}, Pages = {1125--1130}, Pl = {UNITED STATES}, pmid = {10570491}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Fluorescent Dyes); 0 (biotinylated dextran amine); 58-85-5 (Biotin); 9004-54-0 (Dextrans)}, Sb = {IM; S}, Source = {Nat Neurosci. 1999 Dec;2(12):1125-30.}, Status = {MEDLINE}, Title = {Development of ocular dominance columns in the absence of retinal input}, Volume = {2}, Year = {1999}, url = {papers/Crowley_NatNeurosci1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/16051}} @article{Hubener:1999, Abstract = {Crowley and Katz cast doubt on the idea that correlated activity is critical for visual cortex development by showing that ocular dominance maps can emerge without any retinal input.}, Author = {Hubener, M and Bonhoeffer, T}, Con = {Nat Neurosci. 1999 Dec;2(12):1125-30. PMID: 10570491}, Crdt = {1999/11/26 09:00}, Da = {20000118}, Date = {1999 Dec}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20000118}, Edat = {1999/11/26 09:00}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Animals, Newborn; Brain Mapping; Ferrets; Models, Neurological; Neuronal Plasticity/physiology; Retina/growth \& development/*physiology/surgery; Sensory Deprivation/*physiology; Vision, Ocular/*physiology; Visual Cortex/*growth \& development/*physiology; Visual Fields/physiology; Visual Pathways; Visual Perception/physiology}, Mhda = {2001/03/23 10:01}, Month = {Dec}, Number = {12}, Own = {NLM}, Pages = {1043--1045}, Pl = {UNITED STATES}, pmid = {10570475}, Pst = {ppublish}, Pt = {Comment; News}, Sb = {IM; S}, Source = {Nat Neurosci. 1999 Dec;2(12):1043-5.}, Status = {MEDLINE}, Title = {Eyes wide shut}, Volume = {2}, Year = {1999}, url = {papers/Hubener_NatNeurosci1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/15964}} @article{Edelman:1999, Address = {Scripps Research Institute, LaJolla, California 92037, USA.}, Author = {Edelman, G M}, Crdt = {1999/07/23 00:00}, Da = {19990805}, Date = {1999 Jun 30}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2009-03-26 15:30:46 -0400}, Dcom = {19990805}, Edat = {1999/07/23}, Issn = {0077-8923 (Print)}, Jid = {7506858}, Journal = {Ann N Y Acad Sci}, Jt = {Annals of the New York Academy of Sciences}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20051117}, Mh = {Brain/*anatomy \& histology/*physiology; Consciousness/physiology; Humans; Memory/physiology; Neurotransmitter Agents/physiology}, Mhda = {1999/07/23 00:01}, Month = {Jun}, Own = {NLM}, Pages = {68--89}, Pl = {UNITED STATES}, pmid = {10415887}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {0 (Neurotransmitter Agents)}, Sb = {IM}, Source = {Ann N Y Acad Sci. 1999 Jun 30;882:68-89; discussion 128-34.}, Status = {MEDLINE}, Title = {Building a picture of the brain}, Volume = {882}, Year = {1999}, url = {papers/Edelman_AnnNYAcadSci1999.pdf}} @article{Wallace:1997a, Abstract = {The development of multisensory neurons and multisensory integration was examined in the deep layers of the superior colliculus of kittens ranging in age from 3 to 135 d postnatal (dpn). Despite the high proportion of multisensory neurons in adult animals, no such neurons were found during the first 10 d of postnatal life. Rather, all sensory-responsive neurons were unimodal. The first multisensory neurons (somatosensory-auditory) were found at 12 dpn, and visually responsive multisensory neurons were not found until 20 dpn. Early multisensory neurons responded weakly to sensory stimuli, had long latencies, large receptive fields, and poorly developed response selectivities. Most surprising, however, was their inability to integrate combinations of sensory cues to produce significant response enhancement (or depression), a characteristic feature of the adult. Responses to combinations of sensory cues differed little from responses to their modality-specific components. At 28 dpn an abrupt physiological change was noted. Some multisensory neurons now integrated combinations of cross-modality cues and exhibited significant response enhancements when these cues were spatially coincident and response depressions when the cues were spatially disparate. During the next 2 months the incidence of multisensory neurons, and the proportion of these neurons capable of adult-like multisensory integration, gradually increased. Once multisensory integration appeared in a given neuron, its properties changed little with development. Even the youngest integrating neurons showed superadditive enhancements and spatial characteristics of multisensory integration that were indistinguishable from the adult. Nevertheless, neonatal and adult multisensory neurons differed in the manner in which they integrated temporally asynchronous stimuli, a distribution that may reflect the very different behavioral requirements at different ages. The possible maturational role of corticotectal projections in the abrupt gating of multisensory integration is discussed.}, Address = {Department of Neurobiology and Anatomy, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27157, USA.}, Author = {Wallace, M T and Stein, B E}, Crdt = {1997/04/01 00:00}, Da = {19990225}, Date = {1997 Apr 1}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2009-03-26 15:30:46 -0400}, Dcom = {19990225}, Edat = {1997/04/01}, Gr = {EY06562/EY/NEI NIH HHS/United States}, Issn = {0270-6474 (Print)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081121}, Mh = {Acoustic Stimulation; Aging/*physiology; Animals; Animals, Newborn; *Brain Mapping; Cats; Evoked Potentials, Somatosensory; Evoked Potentials, Visual; Neurons, Afferent/*physiology; Photic Stimulation; Superior Colliculi/growth \& development/*physiology; Vision, Ocular/physiology; Visual Perception/physiology}, Mhda = {1997/04/01 00:01}, Month = {Apr}, Number = {7}, Own = {NLM}, Pages = {2429--2444}, Pl = {UNITED STATES}, pmid = {9065504}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {J Neurosci. 1997 Apr 1;17(7):2429-44.}, Status = {MEDLINE}, Title = {Development of multisensory neurons and multisensory integration in cat superior colliculus}, Volume = {17}, Year = {1997}, url = {papers/Wallace_JNeurosci1997.pdf}} @article{Gulrajani:1984, Author = {Gulrajani, R M and Roberge, F A and Savard, P}, Crdt = {1984/12/01 00:00}, Da = {19850403}, Date = {1984 Dec}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {19850403}, Edat = {1984/12/01}, Issn = {0018-9294 (Print)}, Jid = {0012737}, Journal = {IEEE Trans Biomed Eng}, Jt = {IEEE transactions on bio-medical engineering}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Dogs; *Electrocardiography; *Electroencephalography; Humans; Mathematics; Models, Biological; Rabbits; Wolff-Parkinson-White Syndrome/diagnosis}, Mhda = {1984/12/01 00:01}, Month = {Dec}, Number = {12}, Own = {NLM}, Pages = {903--910}, Pl = {UNITED STATES}, pmid = {6396217}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Review}, Rf = {56}, Sb = {IM}, Source = {IEEE Trans Biomed Eng. 1984 Dec;31(12):903-10.}, Status = {MEDLINE}, Title = {Moving dipole inverse ECG and EEG solutions}, Volume = {31}, Year = {1984}, url = {papers/Gulrajani_IEEETransBiomedEng1984.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1109/TBME.1984.325257}} @article{Crowne:1983, Abstract = {Brief deprivation of vision after unilateral lesions of the frontal eye field prevents the appearance of contralateral inattention to visual, auditory, and somatosensory stimuli. The forced circling that accompanies inattention, however, is not affected. An equivalent preoperative period in the dark only partly reduces inattention symptoms. Visual deprivation does not reduce or prevent inattention resulting from lesions of the superior colliculus.}, Author = {Crowne, D P and Richardson, C M and Ward, G}, Crdt = {1983/04/29 00:00}, Da = {19830527}, Date = {1983 Apr 29}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2009-03-26 15:30:46 -0400}, Dcom = {19830527}, Edat = {1983/04/29}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Attention/*physiology; Darkness; Frontal Lobe/*physiology; Male; Movement; Rats; Sensory Deprivation/*physiology; Superior Colliculi/*physiology; Visual Perception/*physiology}, Mhda = {1983/04/29 00:01}, Month = {Apr}, Number = {4596}, Oid = {NASA: 83171425}, Own = {NLM}, Pages = {527--530}, Pl = {UNITED STATES}, pmid = {6836298}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM; S}, Source = {Science. 1983 Apr 29;220(4596):527-30.}, Status = {MEDLINE}, Title = {Brief deprivation of vision after unilateral lesions of the frontal eye field prevents contralateral inattention}, Volume = {220}, Year = {1983}, url = {papers/Crowne_Science1983.pdf}} @article{Drager:1976, Abstract = {In adult mice of the C57BL/6J strain the projection of the visual field was systematically mapped under direct vision. As in other vertebrate species the nasal (anterior) field projected anterolaterally, and the inferior field posterolaterally. Values of magnification-1 (m-1, or degrees of visual field per millimeter tectal surface) were calculated over most of the tectum, for measurements in the coronal and sagittal planes. Whereas m-1 was fairly constant for measurement pairs in sagittal planes, for coronal planes there was a rather large, elongated, horizontally oriented area in the upper field of vision within which m-1 was smaller than elsewhere. In this area m-1 was anisotropic, with a ratio of almost 2:1 between sagittal and coronal planes. In a previously study we had observed that many cells recorded in deeper tectal layers responded to somatosensory stimulation, with whiskers especially conspicuous. In a given penetration perpendicular to the tectal surface, somatosensory receptive fields recorded in the deeper tectum were always concerned with that group of whiskers or with those parts of the body that crossed the regions of visual field represented in the superficial layers directly above. Given this information on the visual coordinates associated with certain somatosensory fields, the detailed mapping of the visual field onto the tectum made it possible to prepare a map of the somatosensory projection on the tectum. The resulting representation differed markedly from maps described for the classic somatosensory pathway. In the tectum the somatosensory map was dictated by the visual-field projection rather than by the peripheral tactile innervation density. Whiskers were thus featured much more prominently in the tectum, and structures close to the eye, such as the pinna and cheek, receive more representation than the tail or hindpaws.}, Author = {Drager, U C and Hubel, D H}, Crdt = {1976/01/01 00:00}, Da = {19760415}, Date = {1976 Jan}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2012-04-13 18:40:15 +0000}, Dcom = {19760415}, Edat = {1976/01/01}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Neurophysiology; retina; mouse; sensory map; topographic map; Superior Colliculus; optic tectum; function; visual system; multisensory integration}, Language = {eng}, Lr = {20071115}, Mh = {Acoustic Stimulation; Animals; Brain Mapping; Light; Mice; Mice, Inbred C57BL; Superior Colliculi/*physiology; Touch/*physiology; Visual Cortex/physiology; *Visual Fields}, Mhda = {1976/01/01 00:01}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {91-101}, Pl = {UNITED STATES}, pmid = {1249606}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {J Neurophysiol. 1976 Jan;39(1):91-101.}, Status = {MEDLINE}, Title = {Topography of visual and somatosensory projections to mouse superior colliculus}, Volume = {39}, Year = {1976}, url = {papers/Drager_JNeurophysiol1976.pdf}} @article{Drager:1975, Abstract = {The superior colliculus was studied in anesthetized mice by recording from single cells and from unit clusters. The topographic representation of the visual filed was similar to what has been found in other mammals, with the temporal part of the contralateral visual field projecting posteriorly and the inferior visual field projecting laterally. At the anterior margin of the tectum receptive fields recorded through the contralateral eye and invaded the ipsilateral visual hemifield for up to 35 degrees, suggesting that the entire visual field through one eye is represented on the contralateral superior colliculus. Cells located closest to the tectal surface had relatively small receptive fields, averaging 9 degrees in center diameter; field sizes increased steadily with depth. The prevailing cell type in the stratum zonal and superficial gray responded best to a small dark or light object of any shape moved slowly through the receptive-field center or to turning a small stationary spot on or off. Large objects or diffuse light were usually much less effective. Less than one-quarter of superficial layer cells showed directional selectivity to a moving object, the majority of these favoring up and nasal movement. The chief visual cell type in the stratum opticum and upper part of the intermediate gray resembled in the newness neurons described for many other vertebrates: they had large receptive fields and responded best to up and nasal movement of a small dark or light object, whose optimal size was similar to the optimum for upper-layer cells. If the same part of the receptive field was repeatedly stimulated there was a marked tendency to habituate. Only very few cels responded to the ipsilateral eye. Intermixed with visual cells in the upper part of the intermediate gray were cells that responded to somatosensory or auditory stimuli. Here bimodal and trimodal cells were also seen. In deeper layers somatosensory and auditory modalities tended to take over. These two modalities were not segregated into sublayers but rather seemed to be arranged in clusters. Responses to somatosensory and auditory stimuli were brisk, showing little habituation to repeated stimulation.}, Author = {Drager, U C and Hubel, D H}, Crdt = {1975/05/01 00:00}, Da = {19750731}, Date = {1975 May}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2012-04-13 18:40:32 +0000}, Dcom = {19750731}, Edat = {1975/05/01}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Neurophysiology; retina; mouse; sensory map; topographic map; Superior Colliculus; optic tectum; function; visual system; multisensory integration}, Language = {eng}, Lr = {20081121}, Mh = {Acoustic Stimulation; Animals; Auditory Perception/*physiology; Brain Mapping; Evoked Potentials; Functional Laterality; Hair/innervation; Mechanoreceptors/physiology; Methionine; Mice/*physiology; Orientation; *Photic Stimulation; Photoreceptor Cells/physiology; Physical Stimulation; Somatosensory Cortex; Sulfur Radioisotopes; Superior Colliculi/*physiology; Touch/*physiology; Visual Fields; Visual Pathways/physiology; Visual Perception/*physiology}, Mhda = {1975/05/01 00:01}, Month = {May}, Number = {3}, Own = {NLM}, Pages = {690-713}, Pl = {UNITED STATES}, pmid = {1127462}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Sulfur Radioisotopes); 63-68-3 (Methionine)}, Sb = {IM; S}, Source = {J Neurophysiol. 1975 May;38(3):690-713.}, Status = {MEDLINE}, Title = {Responses to visual stimulation and relationship between visual, auditory, and somatosensory inputs in mouse superior colliculus}, Volume = {38}, Year = {1975}, url = {papers/Drager_JNeurophysiol1975.pdf}} @article{Drager:1975a, Author = {Drager, U C and Hubel, D H}, Crdt = {1975/01/17 00:00}, Da = {19750419}, Date = {1975 Jan 17}, Date-Added = {2009-03-26 15:18:34 -0400}, Date-Modified = {2011-09-16 13:35:55 -0400}, Dcom = {19750419}, Edat = {1975/01/17}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Neurophysiology; retina; mouse; sensory map; topographic map; Superior Colliculus; optic tectum; function; visual system; multisensory integration}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Auditory Pathways/*physiology; Brain Mapping; Hair; Mice; Mice, Inbred C57BL; Sensory Receptor Cells; Superior Colliculi/cytology/*physiology; *Touch; Visual Pathways/*physiology}, Mhda = {1975/01/17 00:01}, Month = {Jan}, Number = {5488}, Own = {NLM}, Pages = {203--204}, Pl = {ENGLAND}, pmid = {1110771}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Physiology of visual cells in mouse superior colliculus and correlation with somatosensory and auditory input}, Volume = {253}, Year = {1975}, url = {papers/Drager_Nature1975.pdf}} @article{Wilson:2007a, Abstract = {Fluorescent protein (XFP) expression in postnatal neurons allows the anatomical and physiological investigation of identified subpopulations of interneurons with established techniques. However, the spatiotemporal pattern of activity of these XFP neurons within a network and their role in the functional output of the network are more challenging issues to investigate. Here we apply two-photon excitation laser scanning microscopy to mouse spinal cord locomotor networks and present the methodology by which calcium activity can be recorded in XFP-expressing neurons. Such activity can be studied both in relation to neighboring non-XFP neurons in a spinal cord slice preparation and in relation to functional locomotor output monitored by ventral root activity in the intact in vitro spinal cord. Thus the network properties and functional correlates with locomotion of identified populations of interneurons can be studied simultaneously.}, Address = {Department of Anatomy and Neurobiology, 14A1 Sir Charles Tupper Medical Building, 5850 College Street, Dalhousie University, Halifax, Nova Scotia, Canada, B3H 1X5.}, Author = {Wilson, Jennifer M and Dombeck, Daniel A and Diaz-Rios, Manuel and Harris-Warrick, Ronald M and Brownstone, Robert M}, Crdt = {2007/02/17 09:00}, Da = {20070405}, Date = {2007 Apr}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20070710}, Dep = {20070215}, Edat = {2007/02/17 09:00}, Gr = {R01 NS-050943/NS/NINDS NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Activity-development; 21 Calcium imaging; 23 Technique}, Language = {eng}, Lr = {20071203}, Mh = {Animals; Calcium Signaling/*physiology; Coloring Agents; Data Interpretation, Statistical; Glutamate Decarboxylase/metabolism; Green Fluorescent Proteins/*biosynthesis/genetics; Interneurons/physiology; Locomotion/physiology; Luminescent Proteins/*biosynthesis/genetics; Mice; Mice, Inbred ICR; Mice, Transgenic; Microscopy, Confocal/*methods; Nerve Net/*anatomy \& histology/cytology/physiology; Neurons/*physiology; Spinal Cord/metabolism; gamma-Aminobutyric Acid/physiology}, Mhda = {2007/07/11 09:00}, Month = {Apr}, Number = {4}, Own = {NLM}, Pages = {3118--3125}, Phst = {2007/02/15 {$[$}aheadofprint{$]$}}, Pii = {01207.2006}, Pl = {United States}, pmid = {17303810}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Coloring Agents); 0 (Luminescent Proteins); 0 (yellow fluorescent protein, mouse); 147336-22-9 (Green Fluorescent Proteins); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase)}, Sb = {IM}, Status = {MEDLINE}, Title = {Two-photon calcium imaging of network activity in XFP-expressing neurons in the mouse}, Volume = {97}, Year = {2007}, url = {papers/Wilson_JNeurophysiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01207.2006}} @article{Ozden:2008, Abstract = {In vivo multiphoton fluorescence microscopy allows imaging of cellular structures in brain tissue to depths of hundreds of micrometers and, when combined with the use of activity-dependent indicator dyes, opens the possibility of observing intact, functioning neural circuitry. We have developed tools for analyzing in vivo multiphoton data sets to identify responding structures and events in single cells as well as patterns of activity within the neural ensemble. Data were analyzed from populations of cerebellar Purkinje cell dendrites, which generate calcium-based complex action potentials. For image segmentation, active dendrites were identified using a correlation-based method to group covarying pixels. Firing events were extracted from dendritic fluorescence signals with a 95% detection rate and an 8% false-positive rate. Because an event that begins in one movie frame is sometimes not detected until the next frame, detection delays were compensated using a likelihood-based correction procedure. To identify groups of dendrites that tended to fire synchronously, a k-means-based procedure was developed to analyze pairwise correlations across the population. Because repeated runs of k-means often generated dissimilar clusterings, the runs were combined to determine a consensus cluster number and composition. This procedure, termed meta-k-means, gave clusterings as good as individual runs of k-means, was independent of random initial seeding, and allowed the exclusion of outliers. Our methods should be generally useful for analyzing multicellular activity recordings in a variety of brain structures.}, Address = {Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA.}, Author = {Ozden, Ilker and Lee, H Megan and Sullivan, Megan R and Wang, Samuel S-H}, Crdt = {2008/05/24 09:00}, Da = {20080716}, Date = {2008 Jul}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20081105}, Dep = {20080521}, Edat = {2008/05/24 09:00}, Gr = {R01 NS-045193/NS/NINDS NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Calcium imaging; 21 Neurophysiology; 23 Technique}, Language = {eng}, Mh = {Action Potentials/physiology; Animals; Animals, Newborn; Brain Mapping; Calcium Signaling/physiology; Cerebellum/cytology; *Cluster Analysis; Dendrites/physiology; Electrophysiology; Likelihood Functions; Mice; Microscopy, Fluorescence, Multiphoton/*methods; Models, Neurological; Pattern Recognition, Automated; Purkinje Cells/cytology/*physiology}, Mhda = {2008/11/06 09:00}, Month = {Jul}, Number = {1}, Oid = {NLM: PMC2493472 {$[$}Available on 07/01/09{$]$}}, Own = {NLM}, Pages = {495--503}, Phst = {2008/05/21 {$[$}aheadofprint{$]$}}, Pii = {01310.2007}, Pl = {United States}, Pmc = {PMC2493472}, Pmcr = {2009/07/01 00:00}, pmid = {18497355}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Identification and clustering of event patterns from in vivo multiphoton optical recordings of neuronal ensembles}, Volume = {100}, Year = {2008}, url = {papers/Ozden_JNeurophysiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01310.2007}} @article{Niell:2008, Abstract = {Genetic methods available in mice are likely to be powerful tools in dissecting cortical circuits. However, the visual cortex, in which sensory coding has been most thoroughly studied in other species, has essentially been neglected in mice perhaps because of their poor spatial acuity and the lack of columnar organization such as orientation maps. We have now applied quantitative methods to characterize visual receptive fields in mouse primary visual cortex V1 by making extracellular recordings with silicon electrode arrays in anesthetized mice. We used current source density analysis to determine laminar location and spike waveforms to discriminate putative excitatory and inhibitory units. We find that, although the spatial scale of mouse receptive fields is up to one or two orders of magnitude larger, neurons show selectivity for stimulus parameters such as orientation and spatial frequency that is near to that found in other species. Furthermore, typical response properties such as linear versus nonlinear spatial summation (i.e., simple and complex cells) and contrast-invariant tuning are also present in mouse V1 and correlate with laminar position and cell type. Interestingly, we find that putative inhibitory neurons generally have less selective, and nonlinear, responses. This quantitative description of receptive field properties should facilitate the use of mouse visual cortex as a system to address longstanding questions of visual neuroscience and cortical processing.}, Address = {Department of Physiology, W M Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, California 94143-0444, USA.}, Author = {Niell, Cristopher M and Stryker, Michael P}, Crdt = {2008/07/25 09:00}, Da = {20080724}, Date = {2008 Jul 23}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2013-06-10 16:59:46 +0000}, Dcom = {20080902}, Edat = {2008/07/25 09:00}, Gr = {EY02874/EY/NEI NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development; topographic map; Visual Cortex; mouse; extracellular; neurophysiology; in vivo; currOpinRvw}, Language = {eng}, Mh = {Action Potentials/physiology; Animals; Linear Models; Mice; Mice, Inbred C57BL; Neural Inhibition/physiology; Neurons/*classification/*physiology; Nonlinear Dynamics; Orientation/physiology; Photic Stimulation/methods; Psychophysics; Spectrum Analysis; Visual Cortex/*cytology/*physiology; Visual Fields/*physiology}, Mhda = {2008/09/03 09:00}, Month = {Jul}, Number = {30}, Own = {NLM}, Pages = {7520--7536}, Pii = {28/30/7520}, Pl = {United States}, pmid = {18650330}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Highly selective receptive fields in mouse visual cortex}, Volume = {28}, Year = {2008}, url = {papers/Niell_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0623-08.2008}} @article{Sparks:1999, Abstract = {Various conceptual issues have been brought into focus by recent experiments studying the role of the superior colliculus in the control of coordinated movements of the eyes and head, the interaction of saccadic and vergence movements, and cognitive processes influencing the initiation and execution of saccades.}, Address = {Division of Neuroscience, Baylor College of Medicine, Houston, 77030, USA. sparks@saccade.neusc.bcm.tmc.edu}, Author = {Sparks, D L}, Crdt = {1999/12/23 00:00}, Da = {20000113}, Date = {1999 Dec}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2009-03-26 13:49:07 -0400}, Dcom = {20000113}, Edat = {1999/12/23}, Gr = {EY01189-27/EY/NEI NIH HHS/United States}, Issn = {0959-4388 (Print)}, Jid = {9111376}, Journal = {Curr Opin Neurobiol}, Jt = {Current opinion in neurobiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Brain Mapping; Cognition/physiology; Fixation, Ocular/*physiology; *Models, Neurological; Superior Colliculi/*physiology}, Mhda = {1999/12/23 00:01}, Month = {Dec}, Number = {6}, Own = {NLM}, Pages = {698--707}, Pii = {S0959-4388(99)00039-2}, Pl = {ENGLAND}, pmid = {10607648}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Conceptual issues related to the role of the superior colliculus in the control of gaze}, Volume = {9}, Year = {1999}, url = {papers/Sparks_CurrOpinNeurobiol1999.pdf}} @article{Rojas:2006, Abstract = {The rodent whisker sensory system is a commonly used model of cortical processing; however, anesthetics cause profound differences in the shape and timing of evoked responses. Evoked response studies, especially those that use spatial mapping techniques, such as fMRI or optical imaging, will thus show significantly different results depending on the anesthesia used. To describe the effect of behavioral states and commonly used anesthetics, we characterized the early surface-evoked response potentials (ERPs) components (first ERP peak: gamma band 25-45 Hz; fast oscillation: 200-400 Hz; and very fast oscillation: 400-600 Hz) using a 25-channel electrode array on the somatosensory cortex during whisker stimulation. We found significant differences in the ERP shape when ketamine/xylazine, urethane, propofol, isoflurane, and pentobarbital sodium were administered and during sleep and wake states. The highest ERP amplitudes were observed under propofol anesthesia and during quiet sleep. Under isoflurane, the ERP was nearly absent, except for a very late component, which was concombinant with burst synchronization. The slowest responses were seen under urethane and propofol anesthesia. Spatial mapping experiments that use electrical, NMR, or optical techniques must consider the anesthetic dependency of these signals, especially when stimulation protocols or electrical and metabolic responses are compared.}, Address = {VCAPP Department, Washington State University, Pullman, WA 99164, USA.}, Author = {Rojas, Manuel J and Navas, Jinna A and Rector, David M}, Crdt = {2006/02/04 09:00}, Da = {20060608}, Date = {2006 Jul}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20060726}, Dep = {20060202}, Edat = {2006/02/04 09:00}, Gr = {MH60263/MH/NIMH NIH HHS/United States}, Issn = {0363-6119 (Print)}, Jid = {100901230}, Journal = {Am J Physiol Regul Integr Comp Physiol}, Jt = {American journal of physiology. Regulatory, integrative and comparative physiology}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {*Anesthesia, General; Anesthetics, General/*administration \& dosage/*pharmacology; Animals; Biological Markers; Consciousness/drug effects/physiology; Dose-Response Relationship, Drug; Evoked Potentials/*drug effects; Female; Injections, Intramuscular; Injections, Intraperitoneal; Male; Rats; Rats, Sprague-Dawley}, Mhda = {2006/07/27 09:00}, Month = {Jul}, Number = {1}, Own = {NLM}, Pages = {R189-96}, Phst = {2006/02/02 {$[$}aheadofprint{$]$}}, Pii = {00409.2005}, Pl = {United States}, pmid = {16455771}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Anesthetics, General); 0 (Biological Markers)}, Sb = {IM}, Status = {MEDLINE}, Title = {Evoked response potential markers for anesthetic and behavioral states}, Volume = {291}, Year = {2006}, url = {papers/Rojas_AmJPhysiolRegulIntegrCompPhysiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/ajpregu.00409.2005}} @article{Zong:2005, Abstract = {We describe a method termed MADM (mosaic analysis with double markers) in mice that allows simultaneous labeling and gene knockout in clones of somatic cells or isolated single cells in vivo. Two reciprocally chimeric genes, each containing the N terminus of one marker and the C terminus of the other marker interrupted by a loxP-containing intron, are knocked in at identical locations on homologous chromosomes. Functional expression of markers requires Cre-mediated interchromosomal recombination. MADM reveals that interchromosomal recombination can be induced efficiently in vivo in both mitotic and postmitotic cells in all tissues examined. It can be used to create conditional knockouts in small populations of labeled cells, to determine cell lineage, and to trace neuronal connections. To illustrate the utility of MADM, we show that cerebellar granule cell progenitors are fated at an early stage to produce granule cells with axonal projections limited to specific sublayers of the cerebellar cortex.}, Address = {Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.}, Author = {Zong, Hui and Espinosa, J Sebastian and Su, Helen Hong and Muzumdar, Mandar D and Luo, Liqun}, Cin = {Cell. 2005 May 6;121(3):322-3. PMID: 15882615}, Crdt = {2005/05/11 09:00}, Da = {20050510}, Date = {2005 May 6}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20051019}, Edat = {2005/05/11 09:00}, Issn = {0092-8674 (Print)}, Jid = {0413066}, Journal = {Cell}, Jt = {Cell}, Keywords = {23 Technique}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Axons/metabolism; Cell Lineage/genetics; Cerebellar Cortex/cytology/metabolism; Crosses, Genetic; Female; *Gene Silencing; Genetic Markers; Genetic Techniques; Green Fluorescent Proteins/genetics; Integrases/*genetics; Luminescent Proteins/genetics; Male; Mice; Mice, Knockout; Mice, Transgenic; Mitosis/genetics; *Mosaicism; Neurons/cytology; Recombination, Genetic/*genetics; Transgenes/genetics}, Mhda = {2005/10/20 09:00}, Month = {May}, Number = {3}, Own = {NLM}, Pages = {479--492}, Phst = {2004/12/20 {$[$}received{$]$}; 2005/01/30 {$[$}revised{$]$}; 2005/02/10 {$[$}accepted{$]$}}, Pii = {S0092-8674(05)00157-1}, Pl = {United States}, pmid = {15882628}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Genetic Markers); 0 (Luminescent Proteins); 0 (red fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 2.7.7.- (Cre recombinase); EC 2.7.7.- (Integrases)}, Sb = {IM}, Status = {MEDLINE}, Title = {Mosaic analysis with double markers in mice}, Volume = {121}, Year = {2005}, url = {papers/Zong_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.02.012}} @article{Nishiyama:2007, Abstract = {We performed two-photon in vivo imaging of cerebellar climbing fibers (CFs; the terminal arbor of olivocerebellar axons) in adult mice. CF ascending branches innervate Purkinje cells while CF transverse branches show a near complete failure to form conventional synapses. Time-lapse imaging over hours or days revealed that ascending branches were very stable. However, transverse branches were highly dynamic, exhibiting rapid elongation and retraction and varicosity turnover. Thus, different branches of the same axon, with different innervation patterns, display branch type-specific motility in the adult cerebellum. Furthermore, dynamic changes in transverse branch length were almost completely suppressed by pharmacological stimulation of olivary firing.}, Address = {Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, MD 21205, USA.}, Author = {Nishiyama, Hiroshi and Fukaya, Masahiro and Watanabe, Masahiko and Linden, David J}, Crdt = {2007/11/09 09:00}, Da = {20071108}, Date = {2007 Nov 8}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080108}, Edat = {2007/11/09 09:00}, Gr = {P50 MH068830-010003/MH/NIMH NIH HHS/United States; R37 MH051106-15/MH/NIMH NIH HHS/United States; R37 MH51106/MH/NIMH NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20081120}, Mh = {Action Potentials/physiology; Animals; Axons/physiology/*ultrastructure; Cell Movement/*physiology; Cell Shape/physiology; Cerebellar Cortex/*cytology/physiology; Fluorescent Dyes; Growth Cones/physiology/ultrastructure; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Pathways/*cytology/physiology; Neuronal Plasticity/physiology; Olivary Nucleus/*cytology/physiology; Organ Culture Techniques; Organic Chemicals; Presynaptic Terminals/physiology/ultrastructure; Synaptic Transmission/*physiology; Time Factors}, Mhda = {2008/01/09 09:00}, Mid = {NIHMS34121}, Month = {Nov}, Number = {3}, Oid = {NLM: NIHMS34121; NLM: PMC2098835}, Own = {NLM}, Pages = {472--487}, Phst = {2006/11/28 {$[$}received{$]$}; 2007/08/13 {$[$}revised{$]$}; 2007/09/09 {$[$}accepted{$]$}}, Pii = {S0896-6273(07)00708-8}, Pl = {United States}, Pmc = {PMC2098835}, pmid = {17988631}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Alexa594); 0 (Fluorescent Dyes); 0 (Organic Chemicals)}, Sb = {IM}, Status = {MEDLINE}, Title = {Axonal motility and its modulation by activity are branch-type specific in the intact adult cerebellum}, Volume = {56}, Year = {2007}, url = {papers/Nishiyama_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.09.010}} @article{Seo:2008, Abstract = {Game theory analyses optimal strategies for multiple decision makers interacting in a social group. However, the behaviours of individual humans and animals often deviate systematically from the optimal strategies described by game theory. The behaviours of rhesus monkeys (Macaca mulatta) in simple zero-sum games showed similar patterns, but their departures from the optimal strategies were well accounted for by a simple reinforcement-learning algorithm. During a computer-simulated zero-sum game, neurons in the dorsolateral prefrontal cortex often encoded the previous choices of the animal and its opponent as well as the animal's reward history. By contrast, the neurons in the anterior cingulate cortex predominantly encoded the animal's reward history. Using simple competitive games, therefore, we have demonstrated functional specialization between different areas of the primate frontal cortex involved in outcome monitoring and action selection. Temporally extended signals related to the animal's previous choices might facilitate the association between choices and their delayed outcomes, whereas information about the choices of the opponent might be used to estimate the reward expected from a particular action. Finally, signals related to the reward history might be used to monitor the overall success of the animal's current decision-making strategy.}, Address = {Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, SHM B404, New Haven, CT 06510, USA.}, Author = {Seo, Hyojung and Lee, Daeyeol}, Crdt = {2008/10/03 09:00}, Da = {20081029}, Date = {2008 Dec 12}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20081217}, Edat = {2008/10/03 09:00}, Gr = {MH073246/MH/NIMH NIH HHS/United States; NS044270/NS/NINDS NIH HHS/United States}, Issn = {1471-2970 (Electronic)}, Jid = {7503623}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Jt = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, Keywords = {09 Evolutionary dynamics}, Language = {eng}, Lr = {20081230}, Mh = {Animals; Cerebral Cortex/*physiology; Decision Making; Game Theory; *Games, Experimental; Macaca mulatta/*physiology; *Reinforcement (Psychology)}, Mhda = {2008/12/18 09:00}, Month = {Dec}, Number = {1511}, Oid = {NLM: PMC2607365 {$[$}Available on 12/12/09{$]$}}, Own = {NLM}, Pages = {3845--3857}, Pii = {4P6234912X772503}, Pl = {England}, Pmc = {PMC2607365}, Pmcr = {2009/12/12}, pmid = {18829430}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Sb = {IM}, Status = {MEDLINE}, Title = {Cortical mechanisms for reinforcement learning in competitive games}, Volume = {363}, Year = {2008}, url = {papers/Seo_PhilosTransRSocLondBBiolSci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1098/rstb.2008.0158}} @article{Lee:2008, Abstract = {Decision making in a social group has two distinguishing features. First, humans and other animals routinely alter their behavior in response to changes in their physical and social environment. As a result, the outcomes of decisions that depend on the behavior of multiple decision makers are difficult to predict and require highly adaptive decision-making strategies. Second, decision makers may have preferences regarding consequences to other individuals and therefore choose their actions to improve or reduce the well-being of others. Many neurobiological studies have exploited game theory to probe the neural basis of decision making and suggested that these features of social decision making might be reflected in the functions of brain areas involved in reward evaluation and reinforcement learning. Molecular genetic studies have also begun to identify genetic mechanisms for personal traits related to reinforcement learning and complex social decision making, further illuminating the biological basis of social behavior.}, Address = {Yale University School of Medicine, Department of Neurobiology, 333 Cedar Street, SHM B404, New Haven, Connecticut 06510, USA. daeyeol.lee@yale.edu}, Author = {Lee, Daeyeol}, Crdt = {2008/03/28 09:00}, Da = {20080327}, Date = {2008 Apr}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080611}, Dep = {20080326}, Edat = {2008/03/28 09:00}, Gr = {DA024855/DA/NIDA NIH HHS/United States; MH073246/MH/NIMH NIH HHS/United States; R01 NS044270-05/NS/NINDS NIH HHS/United States; RL1 DA024855-01/DA/NIDA NIH HHS/United States}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {09 Evolutionary dynamics}, Language = {eng}, Lr = {20081120}, Mh = {Algorithms; Animals; Cerebral Cortex/*physiology; *Decision Making; *Game Theory; Humans; Reward; *Social Behavior; Social Perception}, Mhda = {2008/06/12 09:00}, Mid = {NIHMS50380}, Month = {Apr}, Number = {4}, Oid = {NLM: NIHMS50380; NLM: PMC2413175}, Own = {NLM}, Pages = {404--409}, Phst = {2008/03/26 {$[$}aheadofprint{$]$}}, Pii = {nn2065}, Pl = {United States}, Pmc = {PMC2413175}, pmid = {18368047}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Review}, Rf = {100}, Sb = {IM}, Status = {MEDLINE}, Title = {Game theory and neural basis of social decision making}, Volume = {11}, Year = {2008}, url = {papers/Lee_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn2065}} @article{Chakravarthy:2008, Abstract = {BACKGROUND: Transgenic mice with mosaic, Golgi-staining-like expression of enhanced green fluorescent protein (EGFP) have been very useful in studying the dynamics of neuronal structure and function. In order to further investigate the molecular events regulating structural plasticity, it would be useful to express multiple proteins in the same sparse neurons, allowing co-expression of functional proteins or co-labeling of subcellular compartments with other fluorescent proteins. However, it has been difficult to obtain reproducible expression in the same subset of neurons for direct comparison of neurons expressing different functional proteins. PRINCIPAL FINDINGS: Here we describe a Cre-transgenic line that allows reproducible expression of transgenic proteins of choice in a small number of neurons of the adult cortex, hippocampus, striatum, olfactory bulb, subiculum, hypothalamus, superior colliculus and amygdala. We show that using these Cre-transgenic mice, multiple Cre-dependent transgenes can be expressed together in the same isolated neurons. We also describe a Cre-dependent transgenic line expressing a membrane associated EGFP (EGFP-F). Crossed with the Cre-transgenic line, EGFP-F expression starts in the adolescent forebrain, is present in dendrites, dendritic protrusions, axons and boutons and is strong enough for acute or chronic in vivo imaging. SIGNIFICANCE: This triple transgenic approach will aid the morphological and functional characterization of neurons in various Cre-dependent transgenic mice.}, Address = {Molecular Visual Plasticity Group, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.}, Author = {Chakravarthy, Sridhara and Keck, Tara and Roelandse, Martijn and Hartman, Robin and Jeromin, Andreas and Perry, Sean and Hofer, Sonja B and Mrsic-Flogel, Thomas and Levelt, Christiaan N}, Crdt = {2008/08/30 09:00}, Da = {20080826}, Date = {2008}, Date-Added = {2009-03-26 13:49:07 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20081218}, Dep = {20080826}, Edat = {2008/08/30 09:00}, Issn = {1932-6203 (Electronic)}, Jid = {101285081}, Journal = {PLoS ONE}, Jt = {PLoS ONE}, Language = {eng}, Mh = {Adult; Animals; Brain/physiology; Gene Expression; Genes, Reporter; Green Fluorescent Proteins/genetics; Humans; Integrases/genetics/metabolism; Mice; Mice, Transgenic; Mosaicism; Neurons/*physiology; Prosencephalon/*physiology}, Mhda = {2008/12/19 09:00}, Number = {8}, Oid = {NLM: PMC2518110}, Own = {NLM}, Pages = {e3059}, Phst = {2007/10/19 {$[$}received{$]$}; 2008/08/04 {$[$}accepted{$]$}}, Pl = {United States}, Pmc = {PMC2518110}, pmid = {18725976}, Pst = {epublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); EC 2.7.7.- (Cre recombinase); EC 2.7.7.- (Integrases)}, Sb = {IM}, Status = {MEDLINE}, Title = {Cre-dependent expression of multiple transgenes in isolated neurons of the adult forebrain}, Volume = {3}, Year = {2008}, url = {papers/Chakravarthy_PLoSONE2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0003059}} @article{Nauhaus:2008, Abstract = {The organization of primary visual cortex (V1) into functional maps makes individual cells operate in a variety of contexts. For instance, some neurons lie in regions of fairly homogeneous orientation preference (iso-orientation domains), while others lie in regions with a variety of preferences (e.g., pinwheel centers). We asked whether this diversity in local map structure correlates with the degree of selectivity of spike responses. We used a combination of imaging and electrophysiology to reveal that neurons in regions of homogeneous orientation preference have much sharper tuning. Moreover, in both monkeys and cats, a common principle links the structure of the orientation map, on the spatial scale of dendritic integration, to the degree of selectivity of individual cells. We conclude that neural computation is not invariant across the cortical surface. This finding must factor into future theories of receptive field wiring and map development.}, Address = {Biomedical Engineering Department, University of California, Los Angeles, CA 90095, USA.}, Author = {Nauhaus, Ian and Benucci, Andrea and Carandini, Matteo and Ringach, Dario L}, Cin = {Neuron. 2008 Mar 13;57(5):627-8. PMID: 18341982}, Crdt = {2008/03/18 09:00}, Da = {20080317}, Date = {2008 Mar 13}, Date-Added = {2009-03-26 12:56:45 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080408}, Edat = {2008/03/18 09:00}, Gr = {R01 EY012816-07/EY/NEI NIH HHS/United States; R01 EY012816-08/EY/NEI NIH HHS/United States; R01 EY018322-01/EY/NEI NIH HHS/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20090316}, Mh = {Animals; Brain Mapping/*methods; Cats; Macaca fascicularis; Neurons/*physiology; Photic Stimulation/methods; Visual Cortex/*physiology; Visual Perception/physiology}, Mhda = {2008/04/09 09:00}, Mid = {NIHMS43365}, Month = {Mar}, Number = {5}, Oid = {NLM: NIHMS43365; NLM: PMC2322861}, Own = {NLM}, Pages = {673--679}, Phst = {2007/10/09 {$[$}received{$]$}; 2007/12/10 {$[$}revised{$]$}; 2008/01/18 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00105-0}, Pl = {United States}, Pmc = {PMC2322861}, pmid = {18341988}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Neuronal selectivity and local map structure in visual cortex}, Volume = {57}, Year = {2008}, url = {papers/Nauhaus_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.01.020}} @article{Mante:2008, Abstract = {Functional models of the early visual system should predict responses not only to simple artificial stimuli but also to sequences of complex natural scenes. An ideal testbed for such models is the lateral geniculate nucleus (LGN). Mechanisms shaping LGN responses include the linear receptive field and two fast adaptation processes, sensitive to luminance and contrast. We propose a compact functional model for these mechanisms that operates on sequences of arbitrary images. With the same parameters that fit the firing rate responses to simple stimuli, it predicts the bulk of the firing rate responses to complex stimuli, including natural scenes. Further improvements could result by adding a spiking mechanism, possibly one capable of bursts, but not by adding mechanisms of slow adaptation. We conclude that up to the LGN the responses to natural scenes can be largely explained through insights gained with simple artificial stimuli.}, Address = {The Smith-Kettlewell Eye Research Institute, 2318 Fillmore Street, San Francisco, CA 94115, USA. valerio@monkeybiz.stanford.edu}, Author = {Mante, Valerio and Bonin, Vincent and Carandini, Matteo}, Cin = {Neuron. 2008 May 22;58(4):467-9. PMID: 18498729}, Crdt = {2008/05/24 09:00}, Da = {20080523}, Date = {2008 May 22}, Date-Added = {2009-03-26 12:56:45 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080625}, Edat = {2008/05/24 09:00}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Mh = {Action Potentials/physiology; *Adaptation, Physiological; Animals; Brain Mapping; Cats; Geniculate Bodies/cytology/*physiology; *Models, Neurological; Neurons/physiology; Nonlinear Dynamics; Photic Stimulation/methods; Predictive Value of Tests; Reaction Time/physiology; Reproducibility of Results; Space Perception/physiology; Visual Fields/physiology; Visual Pathways/physiology; Visual Perception/*physiology}, Mhda = {2008/06/26 09:00}, Month = {May}, Number = {4}, Own = {NLM}, Pages = {625--638}, Phst = {2007/12/20 {$[$}received{$]$}; 2008/02/29 {$[$}revised{$]$}; 2008/03/14 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00257-2}, Pl = {United States}, pmid = {18498742}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Functional mechanisms shaping lateral geniculate responses to artificial and natural stimuli}, Volume = {58}, Year = {2008}, url = {papers/Mante_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.03.011}} @article{Holekamp:2008, Abstract = {Unraveling the functions of the diverse neural types in any local circuit ultimately requires methods to record from most or all of its cells simultaneously. One promising approach to this goal is fluorescence imaging, but existing methods using laser-scanning microscopy (LSM) are severely limited in their ability to resolve rapid phenomena, like neuronal action potentials, over wide fields. Here we present a microscope that rapidly sections a three-dimensional volume using a thin illumination sheet whose position is rigidly coupled to the objective and aligned with its focal plane. We demonstrate that this approach allows exceptionally low-noise imaging of large neuronal populations at pixel rates at least 100-fold higher than with LSM. Using this microscope, we studied the pheromone-sensing neurons of the mouse vomeronasal organ and found that responses to dilute urine are largely or exclusively restricted to cells in the apical layer, the location of V1r-family-expressing neurons.}, Address = {Department of Anatomy and Neurobiology, Washington University in St. Louis School of Medicine, 660 South Euclid, St. Louis, MO 63110, USA.}, Author = {Holekamp, Terrence F and Turaga, Diwakar and Holy, Timothy E}, Crdt = {2008/03/18 09:00}, Da = {20080317}, Date = {2008 Mar 13}, Date-Added = {2009-03-26 12:56:45 -0400}, Date-Modified = {2011-09-12 11:19:15 -0400}, Dcom = {20080408}, Edat = {2008/03/18 09:00}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Mh = {Animals; Female; Fluorescence; Imaging, Three-Dimensional/instrumentation/*methods; Lighting/instrumentation/*methods; Male; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence/instrumentation/*methods; Neurons/chemistry/*cytology/*physiology}, Mhda = {2008/04/09 09:00}, Month = {Mar}, Number = {5}, Own = {NLM}, Pages = {661--672}, Phst = {2007/06/15 {$[$}received{$]$}; 2007/09/26 {$[$}revised{$]$}; 2008/01/07 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00044-5}, Pl = {United States}, pmid = {18341987}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Fast three-dimensional fluorescence imaging of activity in neural populations by objective-coupled planar illumination microscopy}, Volume = {57}, Year = {2008}, url = {papers/Holekamp_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.01.011}} @article{Cang:2008b, Abstract = {The orderly projections from retina to superior colliculus (SC) preserve a continuous retinotopic representation of the visual world. The development of retinocollicular maps depend on a combination of molecular guidance cues and patterned neural activity. Here, we characterize the functional retinocollicular maps in mice lacking the guidance molecules ephrin-A2, -A3, and -A5 and in mice deficient in both ephrin-As and structured spontaneous retinal activity, using a method of Fourier imaging of intrinsic signals. We find that the SC of ephrin-A2/A3/A5 triple knock-out mice contains functional maps that are disrupted selectively along the nasotemporal (azimuth) axis of the visual space. These maps are discontinuous, with patches of SC responding to topographically incorrect locations. The patches disappear in mice that are deficient in both ephrin-As and structured activity, resulting in a near-absence of azimuth map in the SC. These results indicate that ephrin-As guide the formation of functional topography in the SC, and patterned retinal activity clusters cells based on their correlated firing patterns. Comparison of the SC and visual cortical mapping defects in these mice suggests that although ephrin-As are required for mapping in both SC and visual cortex, ephrin-A-independent mapping mechanisms are more important in visual cortex than in the SC.}, Address = {Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208, USA. cang@northwestern.edu}, Author = {Cang, Jianhua and Wang, Lupeng and Stryker, Michael P and Feldheim, David A}, Crdt = {2008/10/24 09:00}, Da = {20081023}, Date = {2008 Oct 22}, Date-Added = {2009-03-26 12:56:45 -0400}, Date-Modified = {2011-09-19 11:17:36 -0400}, Dcom = {20081201}, Edat = {2008/10/24 09:00}, Gr = {EY014689/EY/NEI NIH HHS/United States; EY018621/EY/NEI NIH HHS/United States; EY02874/EY/NEI NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081202}, Mh = {Animals; *Brain Mapping; Diagnostic Imaging/methods; Ephrins/deficiency/*physiology; Fourier Analysis; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Receptors, Nicotinic/deficiency; Superior Colliculi/*growth \& development/metabolism; Visual Cortex/growth \& development/metabolism; Visual Pathways/*growth \& development}, Mhda = {2008/12/17 09:00}, Mid = {NIHMS75267}, Month = {Oct}, Number = {43}, Oid = {NLM: NIHMS75267 {$[$}Available on 04/22/09{$]$}; NLM: PMC2588436 {$[$}Available on 04/22/09{$]$}}, Own = {NLM}, Pages = {11015--11023}, Pii = {28/43/11015}, Pl = {United States}, Pmc = {PMC2588436}, Pmcr = {2009/04/22 00:00}, pmid = {18945909}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Rn = {0 (Ephrins); 0 (Receptors, Nicotinic)}, Sb = {IM}, Status = {MEDLINE}, Title = {Roles of ephrin-As and structured activity in the development of functional maps in the superior colliculus}, Volume = {28}, Year = {2008}, url = {papers/Cang_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2478-08.2008}} @article{Mooser:2004, Abstract = {Feedforward connections are thought to be important in the generation of orientation-selective responses in visual cortex by establishing a bias in the sampling of information from regions of visual space that lie along a neuron's axis of preferred orientation. It remains unclear, however, which structural elements-dendrites or axons-are ultimately responsible for conveying this sampling bias. To explore this question, we have examined the spatial arrangement of feedforward axonal connections that link non-oriented neurons in layer 4 and orientation-selective neurons in layer 2/3 of visual cortex in the tree shrew. Target sites of labeled boutons in layer 2/3 resulting from focal injections of biocytin in layer 4 show an orientation-specific axial bias that is sufficient to confer orientation tuning to layer 2/3 neurons. We conclude that the anisotropic arrangement of axon terminals is the principal source of the orientation bias contributed by feedforward connections.}, Address = {Department of Neurobiology, Box 3209 Duke University Medical Center, Durham, North Carolina 27710, USA.}, Author = {Mooser, Francois and Bosking, William H and Fitzpatrick, David}, Cin = {Nat Neurosci. 2004 Aug;7(8):796-7. PMID: 15280890}, Crdt = {2004/07/20 05:00}, Da = {20040728}, Date = {2004 Aug}, Date-Added = {2009-03-26 12:56:45 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20040930}, Dep = {20040718}, Edat = {2004/07/20 05:00}, Gr = {EY06821/EY/NEI NIH HHS/United States}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Axons/*physiology; Female; Image Processing, Computer-Assisted; Male; Models, Neurological; Orientation/physiology; Tupaiidae/*anatomy \& histology/physiology; Visual Cortex/*anatomy \& histology/physiology; Visual Pathways/*anatomy \& histology/physiology; Visual Perception/*physiology}, Mhda = {2004/10/01 05:00}, Month = {Aug}, Number = {8}, Own = {NLM}, Pages = {872--879}, Phst = {2004/01/30 {$[$}received{$]$}; 2004/06/15 {$[$}accepted{$]$}; 2004/07/18 {$[$}aheadofprint{$]$}}, Pii = {nn1287}, Pl = {United States}, pmid = {15258585}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {A morphological basis for orientation tuning in primary visual cortex}, Volume = {7}, Year = {2004}, url = {papers/Mooser_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1287}} @article{Elstrott:2008, Abstract = {Direction selectivity in the retina requires the asymmetric wiring of inhibitory inputs onto four subtypes of On-Off direction-selective ganglion cells (DSGCs), each preferring motion in one of four cardinal directions. The primary model for the development of direction selectivity is that patterned activity plays an instructive role. Here, we use a unique, large-scale multielectrode array to demonstrate that DSGCs are present at eye opening, in mice that have been reared in darkness and in mice that lack cholinergic retinal waves. These data suggest that direction selectivity in the retina is established largely independent of patterned activity and is therefore likely to emerge as a result of complex molecular interactions.}, Address = {Neuroscience Graduate Program, University of California, San Diego, La Jolla, CA 92093, USA. jelstrott@gmail.com}, Author = {Elstrott, Justin and Anishchenko, Anastasia and Greschner, Martin and Sher, Alexander and Litke, Alan M and Chichilnisky, E J and Feller, Marla B}, Crdt = {2008/05/24 09:00}, Da = {20080523}, Date = {2008 May 22}, Date-Added = {2009-03-26 12:56:45 -0400}, Date-Modified = {2012-04-13 18:43:25 +0000}, Dcom = {20080625}, Edat = {2008/05/24 09:00}, Gr = {EY018003/EY/NEI NIH HHS/United States; R01EY13528/EY/NEI NIH HHS/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development; Structure-Activity Relationship; sensory map; topographic map; visual system; Mouse; Spontaneous activity}, Language = {eng}, Lr = {20081121}, Mh = {Acetylcholine/*metabolism; Action Potentials/physiology; Adaptation, Ocular/physiology; Age Factors; Animals; Animals, Newborn; Mice; Mice, Inbred C57BL; Mice, Knockout; Motion Perception/*physiology; Orientation/*physiology; Photic Stimulation/methods; Receptors, Nicotinic/deficiency; Retina/*cytology; Retinal Ganglion Cells/*physiology; Vision, Ocular/*physiology}, Mhda = {2008/06/26 09:00}, Mid = {NIHMS53069}, Month = {May}, Number = {4}, Oid = {NLM: NIHMS53069 {$[$}Available on 05/22/09{$]$}; NLM: PMC2474739 {$[$}Available on 05/22/09{$]$}}, Own = {NLM}, Pages = {499-506}, Phst = {2007/10/29 {$[$}received{$]$}; 2008/01/28 {$[$}revised{$]$}; 2008/03/18 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00259-6}, Pl = {United States}, Pmc = {PMC2474739}, Pmcr = {2009/05/22 00:00}, pmid = {18498732}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.}, Rn = {0 (Chrnb2 protein, mouse); 0 (Receptors, Nicotinic); 51-84-3 (Acetylcholine)}, Sb = {IM}, Status = {MEDLINE}, Title = {Direction selectivity in the retina is established independent of visual experience and cholinergic retinal waves}, Volume = {58}, Year = {2008}, url = {papers/Elstrott_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.03.013}} @article{Bosking:2008, Abstract = {In this issue of Neuron, Nauhaus et al. use a combination of optical imaging and multiple electrode recording to demonstrate that the orientation tuning of single cells in primary visual cortex is reliably related to the local structure of the orientation preference map in both cats and monkeys.}, Address = {Center for Perceptual Systems, 1 University Station, {\#}A8000, University of Texas, Austin, TX 78712, USA. wbosking@mail.cps.utexas.edu}, Author = {Bosking, William H}, Con = {Neuron. 2008 Mar 13;57(5):673-9. PMID: 18341988}, Crdt = {2008/03/18 09:00}, Da = {20080317}, Date = {2008 Mar 13}, Date-Added = {2009-03-26 12:56:45 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080408}, Edat = {2008/03/18 09:00}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Mh = {Animals; Humans; Neurons/*physiology; Visual Cortex/*physiology; Visual Fields/physiology}, Mhda = {2008/04/09 09:00}, Month = {Mar}, Number = {5}, Own = {NLM}, Pages = {627--628}, Pii = {S0896-6273(08)00180-3}, Pl = {United States}, pmid = {18341982}, Pst = {ppublish}, Pt = {Comment; Journal Article; Review}, Rf = {16}, Sb = {IM}, Status = {MEDLINE}, Title = {V1 neurons: in tune with the neighbors}, Volume = {57}, Year = {2008}, url = {papers/Bosking_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.02.026}} @article{Sudhof:2008, Abstract = {The brain processes information by transmitting signals at synapses, which connect neurons into vast networks of communicating cells. In these networks, synapses not only transmit signals but also transform and refine them. Neurexins and neuroligins are synaptic cell-adhesion molecules that connect presynaptic and postsynaptic neurons at synapses, mediate signalling across the synapse, and shape the properties of neural networks by specifying synaptic functions. In humans, alterations in genes encoding neurexins or neuroligins have recently been implicated in autism and other cognitive diseases, linking synaptic cell adhesion to cognition and its disorders.}, Address = {Neuroscience Institute, Department of Molecular and Cellular Physiology, Stanford University, 1050 Arastradero Road B249, Palo Alto, California 94304, USA. tcs1@stanford.edu}, Author = {Sudhof, Thomas C}, Crdt = {2008/10/17 09:00}, Da = {20081016}, Date = {2008 Oct 16}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081118}, Edat = {2008/10/17 09:00}, Gr = {Howard Hughes Medical Institute/United States}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Mh = {Animals; Autistic Disorder/metabolism; Cell Adhesion Molecules/metabolism; Cognition Disorders/*metabolism; Humans; Membrane Proteins/*metabolism; Nerve Tissue Proteins/*metabolism; Synapses/*metabolism; Synaptic Transmission}, Mhda = {2008/11/19 09:00}, Month = {Oct}, Number = {7215}, Own = {NLM}, Pages = {903--911}, Pii = {nature07456}, Pl = {England}, pmid = {18923512}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review}, Rf = {91}, Rn = {0 (Cell Adhesion Molecules); 0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (neuroligin 1)}, Sb = {IM}, Status = {MEDLINE}, Title = {Neuroligins and neurexins link synaptic function to cognitive disease}, Volume = {455}, Year = {2008}, url = {papers/Sudhof_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07456}} @article{Ryge:2008, Abstract = {BACKGROUND: In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal populations can in combination with global gene expression profiling potentially increase the resolution and specificity of such studies to shed new light on neuronal functions at the cellular level. METHODOLOGY/PRINCIPAL FINDINGS: We examine the microarray gene expression profiles of two distinct neuronal populations in the spinal cord of the neonatal rat, the principal motor neurons and specific interneurons involved in motor control. The gene expression profiles of the respective cell populations were obtained from amplified mRNA originating from 50-250 fluorescently identified and laser microdissected cells. In the data analysis we combine a new microarray normalization procedure with a conglomerate measure of significant differential gene expression. Using our methodology we find 32 genes to be more expressed in the interneurons compared to the motor neurons that all except one have not previously been associated with this neuronal population. As a validation of our method we find 17 genes to be more expressed in the motor neurons than in the interneurons and of these only one had not previously been described in this population. CONCLUSIONS/SIGNIFICANCE: We provide an optimized experimental protocol that allows isolation of gene transcripts from fluorescent retrogradely labeled cell populations in fresh tissue, which can be used to generate amplified aRNA for microarray hybridization from as few as 50 laser microdissected cells. Using this optimized experimental protocol in combination with our microarray analysis methodology we find 49 differentially expressed genes between the motor neurons and the interneurons that reflect the functional differences between these two cell populations in generating and transmitting the motor output in the rodent spinal cord.}, Address = {Mammalian Locomotor Laboratory, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. jesper.ryge@ki.se}, Author = {Ryge, Jesper and Westerdahl, Ann-Charlotte and Alstrom, Preben and Kiehn, Ole}, Crdt = {2008/10/17 09:00}, Da = {20081016}, Date = {2008}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081218}, Dep = {20081015}, Edat = {2008/10/17 09:00}, Issn = {1932-6203 (Electronic)}, Jid = {101285081}, Journal = {PLoS ONE}, Jt = {PLoS ONE}, Language = {eng}, Mh = {Animals; Animals, Newborn; Gene Expression Profiling/*methods; Interneurons/metabolism; Motor Neurons/metabolism; Neurons/*metabolism; Oligonucleotide Array Sequence Analysis; Rats; Spinal Cord/*cytology}, Mhda = {2008/12/19 09:00}, Number = {10}, Oid = {NLM: PMC2566599}, Own = {NLM}, Pages = {e3415}, Phst = {2008/05/16 {$[$}received{$]$}; 2008/09/18 {$[$}accepted{$]$}; 2008/10/15 {$[$}epublish{$]$}}, Pl = {United States}, Pmc = {PMC2566599}, pmid = {18923679}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Gene expression profiling of two distinct neuronal populations in the rodent spinal cord}, Volume = {3}, Year = {2008}, url = {papers/Ryge_PLoSONE2008.pdf}, Bdsk-File-2 = {papers/Ryge_PLoSONE2008.tiff}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0003415}} @article{Haustead:2008, Abstract = {Topographically ordered projections are established by molecular guidance cues and refined by neuronal activity. Retinal input to a primary visual center, the superior colliculus (SC), is bilateral with a dense contralateral projection and a sparse ipsilateral one. Both projections are topographically organized, but in opposing anterior-posterior orientations. This arrangement provides functionally coherent input to each colliculus from the binocular visual field, supporting visual function. When guidance cues involved in contralateral topography (ephrin-As) are absent, crossed retinal ganglion cell (RGC) axons form inappropriate terminations within the SC. However, the organization of the ipsilateral projection relative to the abnormal contralateral input remains unknown, as does the functional capacity of both projections. We show here that in ephrin-A(-/-) mice, the SC contains an expanded, diffuse ipsilateral projection. Electrophysiological recording demonstrated that topography of visually evoked responses recorded from the contralateral superior colliculus of ephrin-A(-/-) mice displayed similar functional disorder in all genotypes, contrasting with their different degrees of anatomical disorder. In contrast, ipsilateral responses were retinotopic in ephrin-A2(-/-) but disorganized in ephrin-A2/A5(-/-) mice. The lack of integration of binocular input resulted in specific visual deficits, which could be reversed by occlusion of one eye. The discrepancy between anatomical and functional topography in both the ipsilateral and contralateral projections implies suppression of inappropriately located terminals. Moreover, the misalignment of ipsilateral and contralateral visual information in ephrin-A2/A5(-/-) mice suggests a role for ephrin-As in integrating convergent visual inputs.}, Address = {School of Animal Biology, Faculty of Medicine and Dentistry, University of Western Australia, Crawley, WA 6009, Australia.}, Author = {Haustead, Daniel J and Lukehurst, Sherralee S and Clutton, Genevieve T and Bartlett, Carole A and Dunlop, Sarah A and Arrese, Catherine A and Sherrard, Rachel M and Rodger, Jennifer}, Crdt = {2008/07/18 09:00}, Da = {20080717}, Date = {2008 Jul 16}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-16 16:17:35 -0400}, Dcom = {20080812}, Edat = {2008/07/18 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {Superior Colliculus; optic tectum; Eph Family; Ephrin-A2; mouse; Mutant Strains; Spontaneous activity; 21 Activity-development; structural remodeling; Structure-Activity Relationship; sensory map; topographic map; retinotopy; Binocular; Monocular; bilateral}, Language = {eng}, Mh = {Animals; Brain Mapping/methods; Ephrin-A2/biosynthesis/*deficiency/*genetics; Ephrin-A5/biosynthesis/*deficiency/*genetics; Functional Laterality/*genetics/physiology; Mice; Mice, Knockout; Nerve Endings/pathology/physiology; Photic Stimulation/methods; Retina/pathology/*physiology; Retinal Ganglion Cells/pathology/physiology; Superior Colliculi/pathology/*physiology; Visual Pathways/pathology/*physiology}, Mhda = {2008/08/13 09:00}, Month = {Jul}, Number = {29}, Own = {NLM}, Pages = {7376--7386}, Pii = {28/29/7376}, Pl = {United States}, pmid = {18632942}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Ephrin-A2); 0 (Ephrin-A5)}, Sb = {IM}, Status = {MEDLINE}, Title = {Functional topography and integration of the contralateral and ipsilateral retinocollicular projections of ephrin-A-/- mice}, Volume = {28}, Year = {2008}, url = {papers/Haustead_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1135-08.2008}} @article{Kayser:2008, Abstract = {Motile dendritic filopodial processes are thought to be precursors of spine synapses, but how motility relates to cell-surface cues required for axon-dendrite recognition and synaptogenesis remains unclear. We demonstrate with dynamic imaging that loss of EphBs results in reduced motility of filopodia in cultured cortical neurons and brain slice. EphB knockdown and rescue experiments during different developmental time windows show that EphBs are required for synaptogenesis only when filopodia are most abundant and motile. In the context of EphB knockdown and reduced filopodia motility, independent rescue of either motility with PAK or of Eph-ephrin binding with an EphB2 kinase mutant is not sufficient to restore synapse formation. Strikingly, the combination of PAK and kinase-inactive EphB2 rescues synaptogenesis. Deletion of the ephrin-binding domain from EphB2 precludes rescue, indicating that both motility and trans-cellular interactions are required. Our findings provide a mechanistic link between dendritic filopodia motility and synapse differentiation.}, Address = {Department of Neuroscience, University of Pennsylvania School of Medicine, 1114 BRB II/III, 421 Curie Boulevard, Philadelphia, PA 19104, USA.}, Author = {Kayser, Matthew S and Nolt, Mark J and Dalva, Matthew B}, Crdt = {2008/07/11 09:00}, Da = {20080710}, Date = {2008 Jul 10}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080812}, Edat = {2008/07/11 09:00}, Gr = {5T32HD007516/HD/NICHD NIH HHS/United States; DA022727/DA/NIDA NIH HHS/United States; HD-026979-0/HD/NICHD NIH HHS/United States; MH073357/MH/NIMH NIH HHS/United States; NS051894-01/NS/NINDS NIH HHS/United States; R01 DA022727-01A1/DA/NIDA NIH HHS/United States; R01 MH073357-03/MH/NIMH NIH HHS/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Language = {eng}, Lr = {20090114}, Mh = {Age Factors; Animals; Animals, Newborn; Cell Movement/*physiology; Cells, Cultured; Cerebral Cortex/cytology; Dendrites/*physiology; Embryo, Mammalian; Mice; Mice, Knockout; Microscopy, Confocal; Mutation; Neurons/cytology; Pseudopodia/*physiology; Rats; Receptors, Eph Family/classification/deficiency/*physiology; Synapses/*physiology; Transfection/methods}, Mhda = {2008/08/13 09:00}, Mid = {NIHMS83540}, Month = {Jul}, Number = {1}, Oid = {NLM: NIHMS83540; NLM: PMC2617787}, Own = {NLM}, Pages = {56--69}, Phst = {2007/10/30 {$[$}received{$]$}; 2008/04/18 {$[$}revised{$]$}; 2008/05/08 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00416-9}, Pl = {United States}, Pmc = {PMC2617787}, pmid = {18614029}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {EC 2.7.1.112 (Receptors, Eph Family)}, Sb = {IM}, Status = {MEDLINE}, Title = {EphB receptors couple dendritic filopodia motility to synapse formation}, Volume = {59}, Year = {2008}, url = {papers/Kayser_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.05.007}} @article{Pasquale:2008, Abstract = {Receptor tyrosine kinases of the Eph family bind to cell surface-associated ephrin ligands on neighboring cells. The ensuing bidirectional signals have emerged as a major form of contact-dependent communication between cells. New findings reveal that Eph receptors and ephrins coordinate not only developmental processes but also the normal physiology and homeostasis of many adult organs. Imbalance of Eph/ephrin function may therefore contribute to a variety of diseases. The challenge now is to better understand the complex and seemingly paradoxical signaling mechanisms of Eph receptors and ephrins, which will enable effective strategies to target these proteins in the treatment of diseases such as diabetes and cancer.}, Address = {Burnham Institute for Medical Research, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA. elenap@burnham.org}, Author = {Pasquale, Elena B}, Crdt = {2008/04/09 09:00}, Da = {20080408}, Date = {2008 Apr 4}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080422}, Edat = {2008/04/09 09:00}, Issn = {1097-4172 (Electronic)}, Jid = {0413066}, Journal = {Cell}, Jt = {Cell}, Language = {eng}, Mh = {Animals; *Cell Communication; Diabetes Mellitus/metabolism; Ephrins/*metabolism; Humans; Neoplasms/metabolism; Nervous System/embryology; Receptors, Eph Family/*metabolism; Signal Transduction}, Mhda = {2008/04/23 09:00}, Month = {Apr}, Number = {1}, Own = {NLM}, Pages = {38--52}, Pii = {S0092-8674(08)00386-3}, Pl = {United States}, pmid = {18394988}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review}, Rf = {94}, Rn = {0 (Ephrins); EC 2.7.1.112 (Receptors, Eph Family)}, Sb = {IM}, Status = {MEDLINE}, Title = {Eph-ephrin bidirectional signaling in physiology and disease}, Volume = {133}, Year = {2008}, url = {papers/Pasquale_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.03.011}} @article{Nern:2008, Abstract = {The organization of neuronal processes into a series of layers is a hallmark of many brain regions. Homophilic cell adhesion molecules of the cadherin family have been implicated in layer choice. How they contribute to the targeting of neurons to distinct layers remains unclear. Here we systematically explore the role of a classical cadherin, Drosophila N-cadherin (CadN), in the targeting of five classes of related neurons to a series of consecutive layers in the fly visual system. We show that CadN is required in lamina neurons at discrete developmental steps but not used in a layer-specific fashion. Local CadN expression patterns correlate with specific growth cone movements, and CadN expression on one growth cone in a specific layer is essential for the targeting of processes of another neuron to this layer. We propose that dynamic regulation of CadN enables this widely expressed protein to mediate specific local interactions during neural circuit assembly.}, Address = {Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.}, Author = {Nern, Aljoscha and Zhu, Yan and Zipursky, S Lawrence}, Cin = {Neuron. 2008 Apr 10;58(1):1-3. PMID: 18400154}, Crdt = {2008/04/11 09:00}, Da = {20080410}, Date = {2008 Apr 10}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080515}, Edat = {2008/04/11 09:00}, Gr = {Howard Hughes Medical Institute/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Language = {eng}, Mh = {Animals; Cadherins/genetics/metabolism/*physiology; Cell Differentiation/physiology; Drosophila; Drosophila Proteins/genetics/metabolism/*physiology; Nerve Net/cytology/physiology; Neurons/*cytology/*metabolism/physiology; Visual Pathways/cytology/physiology}, Mhda = {2008/05/16 09:00}, Month = {Apr}, Number = {1}, Own = {NLM}, Pages = {34--41}, Phst = {2007/12/20 {$[$}received{$]$}; 2008/03/17 {$[$}revised{$]$}; 2008/03/24 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00268-7}, Pl = {United States}, pmid = {18400161}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Cadherins); 0 (Drosophila Proteins)}, Sb = {IM}, Status = {MEDLINE}, Title = {Local N-cadherin interactions mediate distinct steps in the targeting of lamina neurons}, Volume = {58}, Year = {2008}, url = {papers/Nern_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.03.022}} @article{Matthews:2008, Abstract = {In this issue of Neuron, two papers provide new insights into roles for local cadherin-based interactions during axon targeting in the Drosophila visual system. Using high-resolution analyses, Chen and Clandinin identify nonautonomous roles for the atypical cadherin Flamingo during photoreceptor targeting, while Nern et al. demonstrate that local cell type-specific roles for N-cadherin control layer-specific targeting of lamina neurons.}, Address = {Department of Neuroscience, Columbia University Medical Center, 630 W. 168(th) Street, P&S 11-511, New York, NY 10032, USA.}, Author = {Matthews, Benjamin J and Corty, Megan M and Grueber, Wesley B}, Con = {Neuron. 2008 Apr 10;58(1):26-33. PMID: 18400160; Neuron. 2008 Apr 10;58(1):34-41. PMID: 18400161}, Crdt = {2008/04/11 09:00}, Da = {20080410}, Date = {2008 Apr 10}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080515}, Edat = {2008/04/11 09:00}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Cadherins/*physiology; Drosophila; Humans; Photoreceptor Cells, Invertebrate/growth \& development; Vision, Ocular/physiology; Visual Pathways/*growth \& development}, Mhda = {2008/05/16 09:00}, Month = {Apr}, Number = {1}, Own = {NLM}, Pages = {1--3}, Pii = {S0896-6273(08)00270-5}, Pl = {United States}, pmid = {18400154}, Pst = {ppublish}, Pt = {Comment; Journal Article; Review}, Rf = {15}, Rn = {0 (Cadherins)}, Sb = {IM}, Status = {MEDLINE}, Title = {Of cartridges and columns: new roles for cadherins in visual system development}, Volume = {58}, Year = {2008}, url = {papers/Matthews_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.03.024}} @article{Chen:2008, Abstract = {Quantitative differences in cadherin activity have been proposed to play important roles in patterning connections between pre- and postsynaptic neurons. However, no examples of such a function have yet been described, and the mechanisms that would allow such differences to direct growth cones to specific synaptic targets are unknown. In the Drosophila visual system, photoreceptors are genetically programmed to make a complex, stereotypic set of synaptic connections. Here we show that the atypical cadherin Flamingo functions as a short-range, homophilic signal, passing between specific R cell growth cones to influence their choice of postsynaptic partners. We find that individual growth cones are sensitive to differences in Flamingo activity through opposing interactions between neighboring cells and require these interactions to be balanced in order to extend along the appropriate trajectory.}, Address = {Department of Neurobiology, Stanford University, Stanford, CA 94305, USA.}, Author = {Chen, Pei-Ling and Clandinin, Thomas R}, Cin = {Neuron. 2008 Apr 10;58(1):1-3. PMID: 18400154}, Crdt = {2008/04/11 09:00}, Da = {20080410}, Date = {2008 Apr 10}, Date-Added = {2009-03-26 12:50:06 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080515}, Edat = {2008/04/11 09:00}, Gr = {R01 EY015231/EY/NEI NIH HHS/United States; R01 EY015231-01A1/EY/NEI NIH HHS/United States; R01 EY015231-02/EY/NEI NIH HHS/United States; R01 EY015231-03/EY/NEI NIH HHS/United States; R01 EY015231-04/EY/NEI NIH HHS/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Cadherins/genetics/*physiology; Drosophila; Drosophila Proteins/genetics/*physiology; Growth Cones/metabolism/physiology; Photoreceptor Cells, Invertebrate/*growth \& development/*physiology; Visual Pathways/growth \& development/metabolism}, Mhda = {2008/05/16 09:00}, Mid = {NIHMS46997}, Month = {Apr}, Number = {1}, Oid = {NLM: NIHMS46997 {$[$}Available on 04/10/09{$]$}; NLM: PMC2494600 {$[$}Available on 04/10/09{$]$}}, Own = {NLM}, Pages = {26--33}, Phst = {2007/08/15 {$[$}received{$]$}; 2007/11/30 {$[$}revised{$]$}; 2008/01/04 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00038-X}, Pl = {United States}, Pmc = {PMC2494600}, Pmcr = {2009/04/10 00:00}, pmid = {18400160}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Cadherins); 0 (Drosophila Proteins); 0 (stan protein, Drosophila)}, Sb = {IM}, Status = {MEDLINE}, Title = {The cadherin Flamingo mediates level-dependent interactions that guide photoreceptor target choice in Drosophila}, Volume = {58}, Year = {2008}, url = {papers/Chen_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.01.007}} @article{Felsen:2008, Abstract = {Deciding in which direction to move is a ubiquitous feature of animal behavior, but the neural substrates of locomotor choices are not well understood. The superior colliculus (SC) is a midbrain structure known to be important for controlling the direction of gaze, particularly when guided by visual or auditory cues, but which may play a more general role in behavior involving spatial orienting. To test this idea, we recorded and manipulated activity in the SC of freely moving rats performing an odor-guided spatial choice task. In this context, not only did a substantial majority of SC neurons encode choice direction during goal-directed locomotion, but many also predicted the upcoming choice and maintained selectivity for it after movement completion. Unilateral inactivation of SC activity profoundly altered spatial choices. These results indicate that the SC processes information necessary for spatial locomotion, suggesting a broad role for this structure in sensory-guided orienting and navigation.}, Address = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. felsen@cshl.edu}, Author = {Felsen, Gidon and Mainen, Zachary F}, Cin = {Neuron. 2008 Oct 9;60(1):7-8. PMID: 18940583}, Crdt = {2008/10/23 09:00}, Da = {20081022}, Date = {2008 Oct 9}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081106}, Edat = {2008/10/23 09:00}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20090101}, Mh = {Animals; Choice Behavior/*physiology; Male; Motor Activity/*physiology; Neurons/*physiology; Odors; Orientation/physiology; Rats; Rats, Long-Evans; Smell/*physiology; Space Perception/physiology; Superior Colliculi/*physiology}, Mhda = {2008/11/07 09:00}, Mid = {NIHMS74834}, Month = {Oct}, Number = {1}, Oid = {NLM: NIHMS74834 {$[$}Available on 10/09/09{$]$}; NLM: PMC2612727 {$[$}Available on 10/09/09{$]$}}, Own = {NLM}, Pages = {137--148}, Phst = {2008/05/13 {$[$}received{$]$}; 2008/08/01 {$[$}revised{$]$}; 2008/09/05 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00769-1}, Pl = {United States}, Pmc = {PMC2612727}, Pmcr = {2009/10/09}, pmid = {18940594}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {Neuron. 2008 Oct 9;60(1):137-48.}, Status = {MEDLINE}, Title = {Neural substrates of sensory-guided locomotor decisions in the rat superior colliculus}, Volume = {60}, Year = {2008}, url = {papers/Felsen_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.09.019}} @article{Krauzlis:2008, Abstract = {The neural mechanisms that decide when and where to walk are not well understood. In this issue of Neuron, Felsen and Mainen use an olfactory-guided orienting task to show that the superior colliculus is necessary in rodents for the normal execution of spatial locomotor choices.}, Address = {Systems Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. rich@salk.edu}, Author = {Krauzlis, Richard J and Lovejoy, Lee P}, Con = {Neuron. 2008 Oct 9;60(1):137-48. PMID: 18940594}, Crdt = {2008/10/23 09:00}, Da = {20081022}, Date = {2008 Oct 9}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081106}, Edat = {2008/10/23 09:00}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology}, Language = {eng}, Mh = {Animals; Humans; Motor Activity/physiology; Orientation/physiology; Space Perception/physiology; Superior Colliculi/physiology; Walking/*physiology}, Mhda = {2008/11/07 09:00}, Month = {Oct}, Number = {1}, Own = {NLM}, Pages = {7--8}, Pii = {S0896-6273(08)00811-8}, Pl = {United States}, pmid = {18940583}, Pst = {ppublish}, Pt = {Comment; Journal Article; Review}, Rf = {15}, Sb = {IM}, Source = {Neuron. 2008 Oct 9;60(1):7-8.}, Status = {MEDLINE}, Title = {Walk this way}, Volume = {60}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.09.032}} @article{Lemke:2005, Abstract = {The sensory and motor components of nervous systems are connected topographically and contain neural maps of the external world. The paradigm for such maps is the precisely ordered wiring of the output cells of the eye to their synaptic targets in the tectum of the midbrain. The retinotectal map is organized in development through the graded activity of Eph receptor tyrosine kinases and their ephrin ligands. These signaling proteins are arrayed in complementary expression gradients along the orthogonal axes of the retina and tectum, and provide both input and recipient cells with Cartesian coordinates that specify their location. Molecular genetic studies in the mouse indicate that these coordinates are interpreted in the context of neuronal competition for termination sites in the tectum. They further suggest that order in the retinotectal map is determined by ratiometric rather than absolute difference comparisons in Eph signaling along the temporal-nasal and dorsal-ventral axes of the eye.}, Address = {Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA. lemke@salk.edu}, Author = {Lemke, Greg and Reber, Michael}, Crdt = {2005/10/11 09:00}, Da = {20051011}, Date = {2005}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2013-08-27 20:04:57 +0000}, Dcom = {20060112}, Edat = {2005/10/11 09:00}, Issn = {1081-0706 (Print)}, Jid = {9600627}, Journal = {Annu Rev Cell Dev Biol}, Jt = {Annual review of cell and developmental biology}, Keywords = {topographic map; review literature; visual system; optic tectum; superior colliculus; currOpinRvw}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Ephrins/genetics/metabolism; Models, Statistical; *Molecular Biology; Receptors, Eph Family/*metabolism; Retina/cytology/*embryology/metabolism; Superior Colliculi/embryology/metabolism}, Mhda = {2006/01/13 09:00}, Own = {NLM}, Pages = {551--580}, Pl = {United States}, pmid = {16212507}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {103}, Rn = {0 (Ephrins); EC 2.7.1.112 (Receptors, Eph Family)}, Sb = {IM}, Source = {Annu Rev Cell Dev Biol. 2005;21:551-80.}, Status = {MEDLINE}, Title = {Retinotectal mapping: new insights from molecular genetics}, Volume = {21}, Year = {2005}, url = {papers/Lemke_AnnuRevCellDevBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.cellbio.20.022403.093702}} @article{Mrsic-Flogel:2005, Abstract = {During the development of the mammalian retinocollicular projection, a coarse retinotopic map is set up by the graded distribution of axon guidance molecules. Subsequent refinement of the initially diffuse projection has been shown to depend on the spatially correlated firing of retinal ganglion cells. In this scheme, the abolition of patterned retinal activity is not expected to influence overall retinotopic organization, but this has not been investigated. We used optical imaging of intrinsic signals to visualize the complete retinotopic map in the superior colliculus (SC) of mice lacking early retinal waves, caused by the deletion of the beta2 subunit of the nicotinic acetylcholine receptor. As expected from previous anatomical studies in the SC of beta2(-/-) mice, regions activated by individual visual stimuli were much larger and had less sharp borders than those in wild-type mice. Importantly, however, we also found systematic distortions of the entire retinotopic map: the map of visual space was expanded anteriorly and compressed posteriorly. Thus, patterned neuronal activity in the early retina has a substantial influence on the coarse retinotopic organization of the SC.}, Address = {Max-Planck-Institut fur Neurobiologie, D-82152 Martinsried, Germany. flogel@neuro.mpg.de}, Author = {Mrsic-Flogel, Thomas D and Hofer, Sonja B and Creutzfeldt, Claire and Cloez-Tayarani, Isabelle and Changeux, Jean-Pierre and Bonhoeffer, Tobias and Hubener, Mark}, Crdt = {2005/07/22 09:00}, Da = {20050721}, Date = {2005 Jul 20}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2013-05-21 20:36:03 +0000}, Dcom = {20060215}, Edat = {2005/07/22 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology; retinal wave paper; Spontaneous activity; Acetylcholine; optical physiology; intrinsic signal; imaging; Superior Colliculus; optic tectum; optical imaging; currOpinRvw}, Language = {eng}, Lr = {20071115}, Mh = {Animals; *Brain Mapping; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Receptors, Nicotinic/genetics; Retina/*cytology/*growth \& development/physiology; Retinal Ganglion Cells/physiology; Superior Colliculi/*cytology/*growth \& development/physiology; Visual Pathways/cytology/growth \& development/physiology}, Mhda = {2006/02/16 09:00}, Month = {Jul}, Number = {29}, Own = {NLM}, Pages = {6921--6928}, Pii = {25/29/6921}, Pl = {United States}, pmid = {16033902}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Chrnb2 protein, mouse); 0 (Receptors, Nicotinic)}, Sb = {IM}, Source = {J Neurosci. 2005 Jul 20;25(29):6921-8.}, Status = {MEDLINE}, Title = {Altered map of visual space in the superior colliculus of mice lacking early retinal waves}, Volume = {25}, Year = {2005}, url = {papers/Mrsic-Flogel_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1555-05.2005}} @article{OLeary:2005, Abstract = {This chapter summarizes mechanisms that control the development of retinotopic maps in the brain, focusing on work from our laboratory using as models the projection of retinal ganglion cells (RGCs) to the chick optic tectum (OT) or rodent superior colliculus (SC). The formation of a retinotopic map involves the establishment of an initial, very coarse map that subsequently undergoes large-scale remodeling to generate a refined map. All arbors are formed by interstitial branches that form in a topographically biased manner along RGC axons that overshoot their correct termination zone (TZ) along the anterior-posterior (A-P) axis of the OT/SC. The interstitial branches exhibit directed growth along the lateral-medial (L-M) axis of the OT/SC to position the branch at the topographically correct location, where it arborizes to form the TZ. EphA receptors and ephrin-A ligands control in part RGC axon mapping along the A-P axis by inhibiting branching and arborization posterior to the correct TZ. Ephrin-B1 acts bifunctionally through EphB forward signaling to direct branches along the L-M axis of the OT/SC to their topographically correct site. Computational modeling indicates that multiple graded activities are required along each axis to generate a retinotopic map, and makes several predictions, including: the progressive addition of ephrin-As within the OT/SC, due to its expression on RGC axon branches and arbors, is required to increase topographic specificity in branching and arborization as well as eliminate the initial axon overshoot, and that interactions amongst RGC axons that resemble correlated neural activity are required to drive retinotopic refinement. Analyses of mutant mice that lack early spontaneous retinal waves that correlate activity amongst neighboring RGCs, confirm this modeling prediction and show that correlated activity during an early brief critical period is required to drive the large-scale remodeling of the initially topographically coarse projection into a refined one. In summary, multiple graded guidance molecules, retinal waves and correlated spontaneous RGC activity cooperate to generate retinotopic maps.}, Address = {Molecular Neurobiology Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. doleary@salk.edu}, Author = {O'Leary, Dennis D M and McLaughlin, Todd}, Crdt = {2004/12/08 09:00}, Da = {20041207}, Date = {2005}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20050222}, Edat = {2004/12/08 09:00}, Gr = {R01 EY07025/EY/NEI NIH HHS/United States}, Issn = {0079-6123 (Print)}, Jid = {0376441}, Journal = {Prog Brain Res}, Jt = {Progress in brain research}, Language = {eng}, Lr = {20071114}, Mh = {Aging/*physiology; Animals; Brain/*embryology/*growth \& development; Embryonic Development; Ephrins/metabolism; Receptors, Eph Family/metabolism; Retina/*embryology/*growth \& development/physiology; Visual Pathways/*embryology/*growth \& development}, Mhda = {2005/02/23 09:00}, Own = {NLM}, Pages = {43--65}, Pii = {S0079612304470058}, Pl = {Netherlands}, pmid = {15581697}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {114}, Rn = {0 (Ephrins); EC 2.7.1.112 (Receptors, Eph Family)}, Sb = {IM}, Source = {Prog Brain Res. 2005;147:43-65.}, Status = {MEDLINE}, Title = {Mechanisms of retinotopic map development: Ephs, ephrins, and spontaneous correlated retinal activity}, Volume = {147}, Year = {2005}, url = {papers/O'Leary_ProgBrainRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0079-6123(04)47005-8}} @article{Reber:2004, Abstract = {The highly ordered wiring of retinal ganglion cell (RGC) neurons in the eye to their synaptic targets in the superior colliculus of the midbrain has long served as the dominant experimental system for the analysis of topographic neural maps. Here we describe a quantitative model for the development of one arm of this map--the wiring of the nasal-temporal axis of the retina to the caudal-rostral axis of the superior colliculus. The model is based on RGC-RGC competition that is governed by comparisons of EphA receptor signalling intensity, which are made using ratios of, rather than absolute differences in, EphA signalling between RGCs. Molecular genetic experiments, exploiting a combinatorial series of EphA receptor knock-in and knockout mice, confirm the salient predictions of the model, and show that it both describes and predicts topographic mapping.}, Address = {Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA.}, Author = {Reber, Michael and Burrola, Patrick and Lemke, Greg}, Crdt = {2004/10/16 09:00}, Da = {20041014}, Date = {2004 Oct 14}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20041122}, Edat = {2004/10/16 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Genotype; Mice; Mice, Knockout; Mice, Transgenic; *Models, Neurological; Neural Pathways/*physiology; RNA, Messenger/genetics/metabolism; Receptors, Eph Family/deficiency/genetics/*metabolism; Retinal Ganglion Cells/cytology/*physiology; *Signal Transduction; Superior Colliculi/cytology/*physiology}, Mhda = {2004/12/16 09:00}, Month = {Oct}, Number = {7010}, Own = {NLM}, Pages = {847--853}, Phst = {2004/06/04 {$[$}received{$]$}; 2004/08/09 {$[$}accepted{$]$}}, Pii = {nature02957}, Pl = {England}, pmid = {15483613}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (RNA, Messenger); EC 2.7.1.112 (Receptors, Eph Family)}, Sb = {IM}, Source = {Nature. 2004 Oct 14;431(7010):847-53.}, Status = {MEDLINE}, Title = {A relative signalling model for the formation of a topographic neural map}, Volume = {431}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature02957}} @article{Kang:2002, Abstract = {We recently reported on the distribution and effects of eye enucleation on the immunoreactivity of calretinin in the superficial layers of the hamster superior colliculus (SC). In the present study, we describe the types of labeled cells and compare this labeling to that of GABA, the major inhibitory neurotransmitter in the central nervous system. An almost complete depletion of calretinin-immunoreactive (IR) fibers in the superficial layers of the contralateral SC was found following unilateral enucleation. On the contralateral SC, many calretinin-IR cells were newly appeared. The majority of the newly-appeared cells had small- to medium-sized round, oval, or vertical fusiform cell bodies. Two-color immunofluorescence revealed that none of these newly-appeared cells were labeled with an antibody to GABA. The present results show that the calretinin-IR cells are unique in the superficial hamster SC when compared to most of the other brain areas, where many calretinin-IR cells are GABAergic interneurons.}, Address = {Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu 702-701, Korea.}, Author = {Kang, Youn-Sil and Kong, Jee-Hyun and Park, Won-Mee and Kwon, Oh-Ju and Lee, Ji-Eun and Kim, Si-Yeol and Jeon, Chang-Jin}, Crdt = {2003/01/11 04:00}, Da = {20030110}, Date = {2002 Dec 31}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:43 -0400}, Dcom = {20030613}, Edat = {2003/01/11 04:00}, Issn = {1016-8478 (Print)}, Jid = {9610936}, Journal = {Mol Cells}, Jt = {Molecules and cells}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Calcium-Binding Protein, Vitamin D-Dependent/*metabolism; Cricetinae; Eye Enucleation; Fluorescent Antibody Technique, Indirect; Fluorescent Dyes; Nerve Fibers/metabolism; Nerve Tissue Proteins/*metabolism; Neurons/*metabolism; Parvalbumins/metabolism; Perfusion; Retinal Ganglion Cells/metabolism; Superior Colliculi/*metabolism; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2003/06/14 05:00}, Month = {Dec}, Number = {3}, Own = {NLM}, Pages = {361--366}, Pl = {Korea (South)}, pmid = {12521298}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Calcium-Binding Protein, Vitamin D-Dependent); 0 (Fluorescent Dyes); 0 (Nerve Tissue Proteins); 0 (Parvalbumins); 0 (calretinin); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Source = {Mol Cells. 2002 Dec 31;14(3):361-6.}, Status = {MEDLINE}, Title = {Morphology of calretinin-immunoreactive neurons in the superficial layers of hamster superior colliculus after enucleation: lack of co-localization with GABA}, Volume = {14}, Year = {2002}} @article{Munoz:2002, Abstract = {By the time you have reached this point, your daily count of alternating saccades and fixations will have increased considerably. So too will have your understanding of the dynamic interactions model. In the superior colliculi, visual fixation and saccadic initiation may be viewed as independent motor plans that compete for dominance across the intermediate layers. Extrinsic input modifies a point location on the retinotopic motor map that is shaped into a motor plan through the intrinsic circuitry of the superior colliculi. Independent motor plans compete for selection in a push-pull fashion and when a saccadic plan ultimately reaches threshold, it produces a strong burst of action potentials that shuts down the remaining regions of the intermediate layers. Modifying the activity of the intermediate layers changes these dynamic interactions in predictable ways. Enhancing the activity of one region facilitates nearby locations and inhibits distant locations. Diminishing the activity of one region inhibits nearby locations and facilitates distant locations. Such effects have been demonstrated in the neurophysiological activity of single cells (Munoz and Istvan, 1998; Olivier et al., 1999) and in behavior (Hikosaka and Wurtz, 1985; Munoz and Wurtz, 1993b). In addition to explaining visual fixation and saccadic initiation during basic saccadic tasks, the dynamic interactions model can explain changes in the timing of saccadic initiation that are observed when this task is modified. Namely, the gap effect, or decreased saccadic reaction times as a consequence of a gap period, occurs because removing fixation decreases the activity of fixation regions and, correspondingly, increases the excitability of saccadic regions. Express saccades, are a special instance of such dynamic interactions, in which decreased fixation activity and heightened motor preparation signals cause the target-related activity to be translated into a saccadic signal immediately. Finally, the slowing of saccadic initiation for antisaccades, can be interpreted as the consequence of multiple competing signals across the intermediate layers. It should be emphasized that the dynamic interactions that we have described in this chapter are not limited to the superior colliculi. On the contrary, similar interactions take place at many levels of the neuraxis (Moschovakis et al., 1996; Leigh and Zee, 1999; Schall and Thompson, 1999; Hikosaka et al., 2000; Munoz et al., 2000; Glimcher, 2001; Scudder et al., 2002). At this juncture, however, the dynamic interactions involved in producing visual fixation and saccadic initiation are better understood in the superior colliculi because of its well-organized motor map and its well-characterized neuronal elements. Although we are a long way from understanding how the brain controls visual fixation and saccadic initiation, we have made substantial progress in understanding these behaviors in the superior colliculi.}, Address = {Centre for Neuroscience Studies, CIHR Group in Sensory-Motor Systems, Department of Physiology, Queen's University, Kingston, ON K7L 3N6, Canada. doug@eyeml.queensu.ca}, Author = {Munoz, Douglas P and Fecteau, Jillian H}, Crdt = {2003/01/02 04:00}, Da = {20030101}, Date = {2002}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:43 -0400}, Dcom = {20030127}, Edat = {2003/01/02 04:00}, Issn = {0079-6123 (Print)}, Jid = {0376441}, Journal = {Prog Brain Res}, Jt = {Progress in brain research}, Language = {eng}, Lr = {20071115}, Mh = {Fixation, Ocular/*physiology; Humans; Saccades/*physiology; Superior Colliculi/*physiology}, Mhda = {2003/01/28 04:00}, Own = {NLM}, Pages = {3--19}, Pl = {Netherlands}, pmid = {12508579}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Review}, Rf = {51}, Sb = {IM}, Source = {Prog Brain Res. 2002;140:3-19.}, Status = {MEDLINE}, Title = {Vying for dominance: dynamic interactions control visual fixation and saccadic initiation in the superior colliculus}, Volume = {140}, Year = {2002}} @article{Nakamura:2001, Abstract = {The optic tectum differentiates from the alar plate of the mesencephalon. Here, the molecular mechanisms for differentiation of the tectum are reviewed. Mis-expression of Pax2, Pax5 or En can change the fate of the presumptive diencephalon to become the tectum. En, Fgf8, Pax2 and Pax5, exist in a positive feedback loop for their expression so that mis-expression of any of these genes acts on the feedback loop resulting in induction of the optic tectum in the diencephalon. Otx2 and Gbx2 can repress the expression of each other and contribute to the formation of the posterior border of the tectum. Mis-expression of Otx2 in the metencephalon changed the fate of its alar plate to the tectum. The anterior border of the tectum might be determined as a result of repressive interaction of Pax6 with En1 and Pax2. Along the dorsoventral axis of the mesencephalon, Shh contributes to the ventralization of the tissue, that is, the area affected by Shh differentiates into the tegmentum. It is proposed that the brain vesicle that expresses Otx2, Pax2 and En1 might differentiate into the tectum.}, Address = {Dept of Molecular Neurobiology, Institute of Development, Aging and Cancer, Tohoku University, Seiryo-machi 4-1, Aoba-ku, 980-8575, Sendai, Japan. nakamura@idac.tohoku.ac.jp}, Author = {Nakamura, H}, Crdt = {2001/02/13 11:00}, Da = {20010222}, Date = {2001 Jan}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {20010412}, Edat = {2001/02/13 11:00}, Issn = {0166-2236 (Print)}, Jid = {7808616}, Journal = {Trends Neurosci}, Jt = {Trends in neurosciences}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Antigens, CD; Antigens, Surface/metabolism; B-Cell-Specific Activator Protein; Chick Embryo; DNA-Binding Proteins/metabolism; Diencephalon/embryology/metabolism; Feedback/physiology; Gene Expression Regulation, Developmental/*physiology; Homeodomain Proteins/metabolism; Humans; Mesencephalon/embryology/metabolism; Metencephalon/embryology/metabolism; Neural Tube Defects/metabolism; Nuclear Proteins/metabolism; PAX2 Transcription Factor; Superior Colliculi/*embryology/metabolism; Transcription Factors/*metabolism; Transfection/methods}, Mhda = {2001/04/17 10:01}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {32--39}, Pii = {S0166-2236(00)01676-3}, Pl = {England}, pmid = {11163885}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {79}, Rn = {0 (Antigens, CD); 0 (Antigens, Surface); 0 (B-Cell-Specific Activator Protein); 0 (DNA-Binding Proteins); 0 (GBX2 protein, human); 0 (Homeodomain Proteins); 0 (Nuclear Proteins); 0 (PAX2 Transcription Factor); 0 (PAX2 protein, human); 0 (PAX5 protein, human); 0 (Transcription Factors); 0 (antigens, CD200)}, Sb = {IM}, Source = {Trends Neurosci. 2001 Jan;24(1):32-9.}, Status = {MEDLINE}, Title = {Regionalization of the optic tectum: combinations of gene expression that define the tectum}, Volume = {24}, Year = {2001}} @article{Barker:1998, Abstract = {We have examined the development of parvalbumin immunoreactivity in the superior colliculi (SC) of the perinatal and mature rats and rabbits. In mature animals, parvalbumin-expressing cells (PECs) and neuropil in the retinorecipient layers were distributed in a continuous single band extending throughout the entire extent of the colliculus, whereas those in the intermediate layers formed distinct, radially oriented patches. Parvalbumin was expressed for the first time on postconceptional day 34 (PCD 34, postnatal day 12) and PCD 42 (postnatal day 11) in the SC of rat and rabbit, respectively. During ensuing development, both the thickness of the parvalbumin-expressing band in the retinorecipient layers and the numbers of PECs in this band gradually increased, reaching adultlike values by PCD 44 and PCD 50 in the rat and rabbit, respectively. In the rat, monocular eye enucleations on PCD 23 resulted in approximately 55% reduction in the number of PECs in the retinorecipient layers of the contralateral colliculi examined on PCD 44 or PCD 50. Unilateral ablations of the entire visual cortex on PCD 23 (before the first corticotectal fibers from visual cortices reach the SC) or on PCD 28 (when about half of the corticotectal fibers have reached colliculus) resulted in, respectively, approximately 55% and approximately 25% relative reduction in the number of PECs in the retinorecipient layers of the ipsilateral colliculi examined on PCD 44 or PCD 50. We conclude that the ontogenetic expression of parvalbumin in most of PECs in the retinorecipient collicular layers is induced by the activity of the contralateral retinotectal and/or the activity of the ipsilateral corticotectal afferents.}, Address = {Department of Anatomy and Histology, Institute for Biomedical Research, The University of Sydney, New South Wales, Australia.}, Author = {Barker, D A and Dreher, B}, Crdt = {1998/04/21 02:03}, Da = {19980514}, Date = {1998 Apr 6}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 15:40:21 -0400}, Dcom = {19980514}, Edat = {1998/04/21 02:03}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Age Factors; Animals; Animals, Newborn; Antibodies, Monoclonal; Calcium-Binding Proteins/analysis/biosynthesis/immunology; Denervation; Eye Enucleation; Neurons, Afferent/chemistry; Parvalbumins/analysis/*biosynthesis/immunology; Rabbits/*physiology; Rats; Rats, Sprague-Dawley/*physiology; Superior Colliculi/cytology/*growth \& development/*metabolism; Visual Cortex/surgery}, Mhda = {2000/06/20 09:00}, Month = {Apr}, Number = {2}, Own = {NLM}, Pages = {210--230}, Pii = {10.1002/(SICI)1096-9861(19980406)393:2<210::AID-CNE6>3.0.CO;2-5}, Pl = {UNITED STATES}, pmid = {9548698}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Antibodies, Monoclonal); 0 (Calcium-Binding Proteins); 0 (Parvalbumins)}, Sb = {IM}, Source = {J Comp Neurol. 1998 Apr 6;393(2):210-30.}, Status = {MEDLINE}, Title = {Spatiotemporal patterns of ontogenetic expression of parvalbumin in the superior colliculi of rats and rabbits}, Volume = {393}, Year = {1998}, url = {papers/Barker_JCompNeurol1998.pdf}} @article{Barinaga:1998, Author = {Barinaga, M}, Cin = {Science. 1998 Apr 17;280(5362):359, 361. PMID: 9575075; Science. 1998 Apr 17;280(5362):361. PMID: 9575076}, Con = {Science. 1998 Mar 6;279(5356):1531-3. PMID: 9488651}, Crdt = {1998/03/21 00:00}, Da = {19980318}, Date = {1998 Mar 6}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:47:13 -0400}, Dcom = {19980318}, Edat = {1998/03/21}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Aging; Animals; Auditory Pathways/*physiology; Auditory Perception; Birds/*physiology; Cues; *Memory; Neurons/physiology; *Sound Localization; Superior Colliculi/*physiology; Time Factors; Visual Fields; Visual Pathways/*physiology; Visual Perception}, Mhda = {1998/03/21 00:01}, Month = {Mar}, Number = {5356}, Own = {NLM}, Pages = {1451--1452}, Pl = {UNITED STATES}, pmid = {9508718}, Pst = {ppublish}, Pt = {Comment; News}, Sb = {IM}, Source = {Science. 1998 Mar 6;279(5356):1451-2.}, Status = {MEDLINE}, Title = {Owl study sheds light on how young brains learn}, Volume = {279}, Year = {1998}} @article{Knudsen:1998, Abstract = {In the process of creating a multimodal map of space, auditory-visual neurons in the optic tectum establish associations between particular values of auditory spatial cues and locations in the visual field. In the barn owl, tectal neurons reveal these associations in the match between their tuning for interaural time differences (ITDs) and the locations of their visual receptive fields (VRFs). In young owls ITD-VRF associations can be adjusted by experience over a wide range, but the range of adjustment normally becomes quite restricted in adults. This normal range of adjustment in adults was greatly expanded in owls that had previously learned abnormal ITD-VRF associations as juveniles. Thus, the act of learning abnormal associations early in life leaves an enduring trace in this pathway that enables unusual functional connections to be reestablished, as needed, in adulthood, even when the associations represented by these connections have not been used for an extended period of time.}, Address = {Department of Neurobiology, Stanford University School of Medicine, 299 Campus Drive, Fairchild Building D259, Stanford, CA 94305-5125 USA. eknudsen@leland.stanford.edu}, Author = {Knudsen, E I}, Cin = {Science. 1998 Mar 6;279(5356):1451-2. PMID: 9508718}, Crdt = {1998/03/21 00:00}, Da = {19980318}, Date = {1998 Mar 6}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:47:13 -0400}, Dcom = {19980318}, Edat = {1998/03/21}, Gr = {5 R01 DC0155-18/DC/NIDCD NIH HHS/United States}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Adaptation, Physiological; Aging; Animals; Auditory Pathways/*physiology; Auditory Perception; Birds/*physiology; Cues; Memory; *Neuronal Plasticity; Neurons/physiology; *Sound Localization; Superior Colliculi/*physiology; Visual Fields; Visual Pathways/*physiology; Visual Perception}, Mhda = {1998/03/21 00:01}, Month = {Mar}, Number = {5356}, Own = {NLM}, Pages = {1531--1533}, Pl = {UNITED STATES}, pmid = {9488651}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Science. 1998 Mar 6;279(5356):1531-3.}, Status = {MEDLINE}, Title = {Capacity for plasticity in the adult owl auditory system expanded by juvenile experience}, Volume = {279}, Year = {1998}} @article{Wallace:1997, Abstract = {Visual response properties and visuotopic representation in the newborn monkey superior colliculus. J. Neurophysiol. 78: 2732-2741, 1997. Visually responsive neurons were recorded in the superior colliculus (SC) of the newborn rhesus monkey. The receptive fields of these neurons were larger than those in the adult, but already were organized into a well-ordered map of visual space that was very much like that seen in mature animals. This included a marked expansion of the representation of the central 10 degrees of the visual field and a systematic foveal to peripheral increase in receptive field size. Although newborn SC neurons had longer response latencies than did their adult counterparts, they responded vigorously to visual stimuli and exhibited many visual response properties that are characteristic of the adult. These included surround inhibition, within-field spatial summation, within-field spatial inhibition, binocularity, and an adult-like ocular dominance distribution. As in the adult, SC neurons in the newborn preferred a moving visual stimulus and had adult-like selectivities for stimulus speed. The developmentally advanced state of the functional circuitry of the newborn monkey SC contrasts with the comparative immaturity of neurons in its visual cortex. It also contrasts with observations on the state of maturation of the newborn SC in other developmental models (e.g., cat). The observation that extensive visual experience is not necessary for the development of many adult-like SC response properties in the monkey SC may help explain the substantial visual capabilities shown by primates soon after birth.}, Address = {Department of Neurobiology and Anatomy, Bowman Gray School of Medicine/Wake Forest University, Winston-Salem, North Carolina 27157, USA.}, Author = {Wallace, M T and McHaffie, J G and Stein, B E}, Crdt = {1997/11/14 00:00}, Da = {19971222}, Date = {1997 Nov}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:47:13 -0400}, Dcom = {19971222}, Edat = {1997/11/14}, Gr = {EY-06562/EY/NEI NIH HHS/United States; NS-22543/NS/NINDS NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Aging/*physiology; Animals; Animals, Newborn; *Brain Mapping; Cats; Electrolysis; Macaca mulatta; Neurons/*physiology; Photic Stimulation; Reaction Time; Superior Colliculi/growth \& development/*physiology; Visual Fields/physiology; Visual Perception/*physiology}, Mhda = {1997/11/14 00:01}, Month = {Nov}, Number = {5}, Own = {NLM}, Pages = {2732--2741}, Pl = {UNITED STATES}, pmid = {9356422}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM; S}, Source = {J Neurophysiol. 1997 Nov;78(5):2732-41.}, Status = {MEDLINE}, Title = {Visual response properties and visuotopic representation in the newborn monkey superior colliculus}, Volume = {78}, Year = {1997}} @article{Yamagata:1995, Abstract = {In diverse vertebrate species, defined subsets of retinal ganglion cells (RGCs, the neurons that project from retina to brain) are distinguishable on the basis of their dendritic morphology, physiological properties, neurotransmitter content and synaptic targets. Little is known about when this diversity arises, whether diversification requires target-derived signals, and how subtype-specific projection patterns are established. Here, we have used markers for two chemically defined RGC subsets in chick retina to address these issues. Antibodies to substance P (SP) and the nicotine acetylcholine receptor (AChR) beta 2 subunit label two small ( < 10%), mutually exclusive groups of RGCs in mature retina. SP and AChRs accumulate in distinct RGCs before retinotectal synapses have formed. Moreover, both populations of RGCs form in retinae that develop following tectal ablation or transplantation to the coelomic cavity. Thus, RGC subsets acquire distinct neurotransmitter phenotypes in the absence of extraretinal cues. In the mature optic tectum, SP- and AChR-positive RGC axonal arbors are confined to distinct retinorecipient (synaptic) laminae. In the developing tectum, SP- and AChR-positive axons are initially intermingled in a superficial fiber layer, but then enter and arborize in appropriate laminae soon after those laminae form. Importantly, SP-positive axons, which synapse in a superficial lamina, never extend into the deeper, AChR-positive lamina. Tectal interneurons rich in SP receptors are concentrated in the lamina to which SP-positive RGC axons project, and a set of cholinergic (choline acetyltransferase-positive) tectal projection neurons elaborate dendrites in the lamina to which AChR-positive RGC axons project. These populations of tectal neurons, which are likely targets of the RGC subsets, form in tecta that develop following enucleation. Thus, RGCs and their targets can diversify in each others absence. Accordingly, we propose that the lamina-selective connectivity we observe reflects the presence of complementary cues on RGC subsets and their laminar targets.}, Address = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.}, Author = {Yamagata, M and Sanes, J R}, Crdt = {1995/11/01 00:00}, Da = {19960319}, Date = {1995 Nov}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:44:25 -0400}, Dcom = {19960319}, Edat = {1995/11/01}, Issn = {0950-1991 (Print)}, Jid = {8701744}, Journal = {Development}, Jt = {Development (Cambridge, England)}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Cell Differentiation/physiology; Chick Embryo; Choline O-Acetyltransferase/metabolism; Immunohistochemistry; Organ Culture Techniques; Receptors, Cholinergic/metabolism; Retinal Ganglion Cells/*cytology/metabolism/physiology; Substance P/metabolism; Superior Colliculi/cytology}, Mhda = {1995/11/01 00:01}, Month = {Nov}, Number = {11}, Own = {NLM}, Pages = {3763--3776}, Pl = {ENGLAND}, pmid = {8582286}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Receptors, Cholinergic); 33507-63-0 (Substance P); EC 2.3.1.6 (Choline O-Acetyltransferase)}, Sb = {IM}, Source = {Development. 1995 Nov;121(11):3763-76.}, Status = {MEDLINE}, Title = {Target-independent diversification and target-specific projection of chemically defined retinal ganglion cell subsets}, Volume = {121}, Year = {1995}} @article{Benedetti:1995, Abstract = {Different regions of the body of an animal have their own shape and location within visual space. Accordingly, in the superior colliculus there are somatosensory-visual bimodal neurons receiving tactile and visual input from the same region of space. In newborn mice, we changed the position of some body parts within visual space in order to see what happened to the alignment of the somatosensory and visual receptive fields of superior colliculus bimodal neurons. To do this, we modified the shape of the head by displacing the superior vibrissae and the ears, normally in the superior portion of visual space, into the inferior visual space. Analogously, we bent the inferior vibrissae into the superior visual space. At the sixth postnatal week we recorded from somatosensory-visual bimodal neurons of the deep layers of the superior colliculus and found that the tactile and visual receptive fields were aligned. Neurons receiving tactile input from the downward-displaced superior vibrissae and ears showed visual receptive fields in the inferior portion of visual space, whereas neurons receiving input from the upward-displaced inferior vibrissae showed visual receptive fields in the superior visual space. These results show that an experience-dependent interaction between visual and somatosensory inputs occurs during development, and that early exposure to abnormal visual-somatosensory experience modifies the organization of multisensory neurons in the superior colliculus.}, Address = {Dipartimento di Anatomia e Fisiologia Umana, Universita di Torino, Italy.}, Author = {Benedetti, F and Ferro, I}, Crdt = {1995/03/01 00:00}, Da = {19950713}, Date = {1995 Mar 1}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:47:13 -0400}, Dcom = {19950713}, Edat = {1995/03/01}, Issn = {0953-816X (Print)}, Jid = {8918110}, Journal = {Eur J Neurosci}, Jt = {The European journal of neuroscience}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Animals, Newborn; Brain Mapping; Ear/physiology; Head/physiology; Mice; Mice, Inbred C57BL; *Neuronal Plasticity; Neurons, Afferent/physiology; Somatosensory Cortex/*physiology; Superior Colliculi/cytology/*physiology; Vibrissae/physiology; Visual Pathways/*physiology}, Mhda = {1995/03/01 00:01}, Month = {Mar}, Number = {3}, Own = {NLM}, Pages = {412--418}, Pl = {ENGLAND}, pmid = {7773438}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Source = {Eur J Neurosci. 1995 Mar 1;7(3):412-8.}, Status = {MEDLINE}, Title = {The effects of early postnatal modification of body shape on the somatosensory-visual organization in mouse superior colliculus}, Volume = {7}, Year = {1995}} @article{Schmidt-Kastner:1992, Abstract = {The neuron-specific calcium-binding proteins, parvalbumin and calbindin-D-28k, were studied in the subcortical visual system of normal and unilaterally deafferented albino rats. Immunohistochemistry with monoclonal antibodies was used on vibratome sections through optic tract (OT), dorsal lateral geniculate nucleus (dLGN), olivary pretectal nucleus (OPN), and superior colliculus (SC). In controls, OT stained strongly for parvalbumin and weakly for calbindin-D-28k. The dLGN contained a plexus of parvalbumin-positive fibers. In dLGN, calbindin-D-28k-antibodies showed strong labeling of some neurons with long dendrites and weak staining of the cytoplasm in other neurons. In OPN, parvalbumin stained a ring of neurons and terminals in the shell region, whereas calbindin-D-28k was contained in medial cell populations. In SC, parvalbumin was contained in fibers, terminals, and neurons throughout the visual layer. Calbindin-D-28k showed a laminar distribution of neurons with a predominance in deep portions of superficial grey matter and in ventral portions of stratum opticum. Following unilateral deafferentation induced by optic nerve section, retinal axons showed immunohistochemical changes related to Wallerian degeneration and target neurons reacted by changes of calcium-binding proteins. Parvalbumin and calbindin-D-28k immunostaining decreased during Wallerian degeneration of OT. In the deafferented dLGN, immunohistochemical labeling for calbindin-D-28k declined in strongly stained neurons from 4 to 21 days after lesion. Measurement of dendritic length per number of cells or per area of dLGN showed a significant decline for the contralateral side at 4, 8, and 21 days (ANOVA, P less than 0.05). In deafferented OPN, terminal-like staining for parvalbumin decreased and neuronal labeling was enhanced. In deafferented SC, the neuronal and dendritic staining for parvalbumin increased beginning from Day 1 on and persisting at Day 21, whereas fibers and terminal-like elements decreased in staining. Measurement of parvalbumin-positive neurons per area of SC showed a significant increase of labeling in the contralateral side from Day 1 to Day 21 (ANOVA, P less than 0.05). These studies show that cellular responses to deafferentation of visual neurons involve a regulation of calcium-binding proteins. The decline in staining for calbindin-D-28k in dLGN may relate to reduced retinal afferent activity. The progressive cellular changes in parvalbumin staining may be related to unmasking of intrinsic neurons after removal of parvalbumin-containing, afferent fibers and terminals. Additionally, the changes of parvalbumin labeling in SC neurons may reflect a plastic reorganization of local circuits known to occur in rat SC in response to deafferentation.}, Address = {Department of Neurophysiology, Medical Faculty, Ruhr-Universitat Bochum, Germany.}, Author = {Schmidt-Kastner, R and Meller, D and Eysel, U T}, Crdt = {1992/09/01 00:00}, Da = {19921026}, Date = {1992 Sep}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {19921026}, Edat = {1992/09/01}, Issn = {0014-4886 (Print)}, Jid = {0370712}, Journal = {Exp Neurol}, Jt = {Experimental neurology}, Language = {eng}, Lr = {20071115}, Mh = {Afferent Pathways/*physiology; Animals; Antibodies, Monoclonal; Calcium-Binding Protein, Vitamin D-Dependent/analysis/*metabolism; Female; Geniculate Bodies/cytology/*metabolism; Immunoenzyme Techniques; Immunohistochemistry; Male; Neurons/cytology/*metabolism; Olivary Nucleus/cytology/*metabolism; Optic Nerve/*physiology; Parvalbumins/analysis/*metabolism; Rats; Rats, Inbred Strains; Superior Colliculi/cytology/*metabolism; Visual Pathways/cytology/*metabolism}, Mhda = {1992/09/01 00:01}, Month = {Sep}, Number = {3}, Own = {NLM}, Pages = {230--246}, Pl = {UNITED STATES}, pmid = {1397159}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {0 (Antibodies, Monoclonal); 0 (Calcium-Binding Protein, Vitamin D-Dependent); 0 (Parvalbumins); 0 (calbindin)}, Sb = {IM}, Source = {Exp Neurol. 1992 Sep;117(3):230-46.}, Status = {MEDLINE}, Title = {Immunohistochemical changes of neuronal calcium-binding proteins parvalbumin and calbindin-D-28k following unilateral deafferentation in the rat visual system}, Volume = {117}, Year = {1992}} @article{Benedetti:1992, Abstract = {Mice were enucleated bilaterally at birth in order to investigate whether early visual deprivation had any influence on the development of the somatosensory representation in the superior colliculus (SC). Single unit recordings were performed during the 2nd, 3rd, 5th and 8th postnatal week in both normal and enucleated mice. It was found that, in visually deprived mice, there was a dramatic increase of the SC somatosensory units starting from the 3rd postnatal week, as occurs in normal mice. During the 5th and 8th postnatal week, this increase was larger than in normal mice, mainly due to the invasion of the somatosensory input into the superficial layers. In visually deprived mice, both the orientation of the somatosensory map and the magnification of some body parts, such as the upper vibrissae, did not show any difference with respect to normal mice. These results indicate the involvement of both vision-dependent and independent mechanisms in the formation of the SC somatosensory representation. In fact, whereas the segregation of the somatosensory afferents in the deep layers depended on the presence of visual input, the postnatal emergence and the topographic arrangement of the somatosensory map resulted to be independent of vision.}, Address = {Department of Human Anatomy and Physiology, University of Turin, Italy.}, Author = {Benedetti, F}, Crdt = {1992/02/21 00:00}, Da = {19920601}, Date = {1992 Feb 21}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 15:39:04 -0400}, Dcom = {19920601}, Edat = {1992/02/21}, Issn = {0165-3806 (Print)}, Jid = {8908639}, Journal = {Brain Res Dev Brain Res}, Jt = {Brain research. Developmental brain research}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081121}, Mh = {Animals; *Eye Enucleation; Mice; Mice, Inbred C57BL; Superior Colliculi/anatomy \& histology/*physiology; Vibrissae/physiology; Vision, Ocular/*physiology}, Mhda = {1992/02/21 00:01}, Month = {Feb}, Number = {2}, Own = {NLM}, Pages = {173--178}, Pl = {NETHERLANDS}, pmid = {1572062}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {Brain Res Dev Brain Res. 1992 Feb 21;65(2):173-8.}, Status = {MEDLINE}, Title = {The development of the somatosensory representation in the superior colliculus of visually deprived mice}, Volume = {65}, Year = {1992}, url = {papers/Benedetti_BrainResDevBrainRes1992.pdf}} @article{Mize:1992, Abstract = {GABA is an important inhibitory neurotransmitter in the mammalian superior colliculus. As in the lateral geniculate nucleus, GABA immunoreactive neurons in SC are almost all small and are distributed throughout the structure in all mammalian species studied to date. Unlike the LGN, GABA-labeled neurons in SC have a variety of morphologies. These cells have been best characterized in cat, where horizontal and two granule cell morphologies have been identified. Horizontal cells give rise to one class of presynaptic dendrite while granule C cells give rise to another class of spine-like presynaptic dendrite. Granule A cells may be the origin of some GABAergic axon terminals. GABA containing synaptic profiles form serial synapses, providing a possible substrate for disinhibition. The distribution of GABAA and GABAB receptor subtypes appears similar to that of GABA neurons, with the densest distribution found within the superficial gray layer. However, antibody immunocytochemistry of the beta 2 and beta 3 subunits of the GABAA receptor reveals that it is located at both synaptic and non-synaptic sites, and may be associated with membrane adjacent to terminals with either flattened or round vesicles. A few GABA containing neurons in SC colocalize the pentapeptide leucine enkephalin or the calcium binding protein calbindin. However, none appear to co-localize parvalbumin, a situation different from GABA containing interneurons in the LGN and visual cortex. The diversity of GABA neurons in SC rivals that found in visual cortex, although unlike visual cortex, the pattern of co-occurrence does not distinguish GABA cell types in SC. The superior colliculus also differs from both LGN and visual cortex in that GABA and calbindin immunoreactivity is not altered by either long-term occlusion and/or short-term enucleation in adult Rhesus monkeys. No consistent differences have been found in the optical density of GABA labeling in either cells or neuropil. To conclude, GABA neurons in the superior colliculus share some properties like those in LGN and others like those in visual cortex. In other properties, they differ from GABA neurons in both the LGN and visual cortex. The GABA systems in the superior colliculus are similar in all mammalian species studied, suggesting that they are phylogenetically conserved systems which are not amenable to plastic alterations, a situation different to that in the geniculostriate system.}, Address = {Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163.}, Author = {Mize, R R}, Crdt = {1992/01/01 00:00}, Da = {19920820}, Date = {1992}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {19920820}, Edat = {1992/01/01}, Gr = {EY-02973/EY/NEI NIH HHS/United States}, Issn = {0079-6123 (Print)}, Jid = {0376441}, Journal = {Prog Brain Res}, Jt = {Progress in brain research}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Axons/metabolism/ultrastructure; Dendrites/metabolism/ultrastructure; Neurons/metabolism/*ultrastructure; Receptors, GABA-A/metabolism; Retina/metabolism/ultrastructure; Superior Colliculi/*ultrastructure; Synapses/metabolism/ultrastructure; *gamma-Aminobutyric Acid/metabolism}, Mhda = {1992/01/01 00:01}, Own = {NLM}, Pages = {219--248}, Pl = {NETHERLANDS}, pmid = {1321459}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {177}, Rn = {0 (Receptors, GABA-A); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Source = {Prog Brain Res. 1992;90:219-48.}, Status = {MEDLINE}, Title = {The organization of GABAergic neurons in the mammalian superior colliculus}, Volume = {90}, Year = {1992}} @article{Ritter:1991, Abstract = {Capsaicin is a neurotoxin capable of causing degeneration in specific sites throughout the neuraxis, including the suprachiasmatic nucleus (SCh), the ventrolateral geniculate nucleus (VLG), the intergeniculate leaflet (IGL), and the olivary and medial pretectal nuclei (OPT and MPT). In this experiment, we tested the hypothesis that capsaicin-induced terminal degeneration in the SCh, VLG, IGL, OPT, and MPT results from destruction of retinal ganglion cells and their axonal projections to these sites. In the first experiment, silver stains were used to examine degeneration in the retina induced by systemic capsaicin treatment. Capsaicin caused degeneration of ganglion cells, bipolar cells, and nerve terminals in the retina, which could be observed between 2 and 24 hours after treatment. In the second experiment, 15-day-old rat pups were enucleated unilaterally. Five days or 2, 5, or 10 months later, they were injected systemically with capsaicin and killed 6 hours (pups) or 18 hours (adults) later for analysis with a cupric silver stain. In rats of all ages, prior monocular enucleation reduced or eliminated capsaicin-induced degeneration in the contralateral SCh, VLG, IGL, OPT, and MPT. In the third experiment, rat pups were treated systemically with capsaicin or vehicle solution at 12 days of age and given unilateral intravitreal injections of cholera toxin conjugated to horseradish peroxidase (CT-HRP) 3 days prior to sacrifice at 20 days of age. Transport of CT-HRP to the SCh, VLG, IGL, MPT, and OPT was attenuated but not abolished by capsaicin pretreatment. Results suggest that capsaicin causes degeneration in the SCh, VLG, IGL, MPT, and OPT by selective destruction of a subpopulation of retinal ganglion cells with axonal projections to these sites.}, Address = {Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University, Pullman 99164-6520.}, Author = {Ritter, S and Dinh, T T}, Crdt = {1991/06/01 00:00}, Da = {19910926}, Date = {1991 Jun 1}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {19910926}, Edat = {1991/06/01}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Capsaicin/*pharmacology; Female; Geniculate Bodies/cytology; Interneurons/physiology; Male; Nerve Degeneration/*drug effects; Olivary Nucleus/cytology; Optic Nerve/*physiology; Rats; Rats, Inbred Strains; Retina/cytology; Staining and Labeling; Superior Colliculi/cytology; Suprachiasmatic Nucleus/cytology}, Mhda = {1991/06/01 00:01}, Month = {Jun}, Number = {1}, Own = {NLM}, Pages = {79--90}, Pl = {UNITED STATES}, pmid = {1714924}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {404-86-4 (Capsaicin)}, Sb = {IM}, Source = {J Comp Neurol. 1991 Jun 1;308(1):79-90.}, Status = {MEDLINE}, Title = {Prior optic nerve transection reduces capsaicin-induced degeneration in rat subcortical visual structures}, Volume = {308}, Year = {1991}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903080108}} @article{Benedetti:1991, Abstract = {The somatosensory map of the superior colliculus was studied in the mouse during the 2nd and 3rd postnatal weeks, with particular attention to the representation of the vibrissae. The presence of an organized somatosensory projection was not electrophysiologically demonstrable until the beginning of the 3rd postnatal week, in coincidence with the opening of the eyes. Recordings performed during the 2nd postnatal week showed that the collicular units responding to tactile stimuli were rare and functionally immature. Starting from the beginning of the 3rd postnatal week, there was a dramatic increase of the number of somatosensory units and the appearance of an ordered topography, together with the maturation of the neuronal electrical properties. All the features of the adult collicular somatosensory map were found in the 3rd postnatal week, including the magnification of the vibrissae occupying the central portion of the visual field. The functional maturation of the collicular somatosensory map of the mouse is therefore a postnatal event which starts during the 3rd postnatal week, just after the opening of the eyes.}, Address = {Department of Human Anatomy and Physiology, University of Turin, Italy.}, Author = {Benedetti, F}, Crdt = {1991/05/20 00:00}, Da = {19911028}, Date = {1991 May 20}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:44:25 -0400}, Dcom = {19911028}, Edat = {1991/05/20}, Issn = {0165-3806 (Print)}, Jid = {8908639}, Journal = {Brain Res Dev Brain Res}, Jt = {Brain research. Developmental brain research}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Aging/physiology; Animals; Brain Mapping; Electrophysiology; Evoked Potentials, Somatosensory/physiology; Mice; Mice, Inbred C57BL; Neurons/physiology; Physical Stimulation; Superior Colliculi/*growth \& development/physiology; Vibrissae/physiology}, Mhda = {1991/05/20 00:01}, Month = {May}, Number = {1}, Own = {NLM}, Pages = {51--57}, Pl = {NETHERLANDS}, pmid = {1914145}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Source = {Brain Res Dev Brain Res. 1991 May 20;60(1):51-7.}, Status = {MEDLINE}, Title = {The postnatal emergence of a functional somatosensory representation in the superior colliculus of the mouse}, Volume = {60}, Year = {1991}} @article{Olson:1991, Abstract = {In the normal goldfish, neighboring retinal ganglion cells terminate in one small tectal locus to produce the precise retinotopy characteristic of this projection. This can be directly demonstrated by labeling neighboring ganglion cells with small "spot" injections of WGA-HRP, which yield a single small patch of product at the retinotopically appropriate part of the tectum. When the optic nerve is crushed, label from these spot injections was previously found to be widely dispersed during the early phase of regeneration. With time, label subsequently condensed, typically into several discrete patches reminiscent of ocular dominance columns. In this study, we tested whether the formation of these patches required impulse activity by injecting tetrodotoxin (TTX) into the eye during regeneration. We found that impulse blockade completely inhibited the formation of discrete patches while permitting considerable condensation of the label. This implies that these patches are generated by activity but that some map "refinement" utilized cellular processes that are activity independent. This activity-independent condensation progressed at a noticeably slower rate than the equivalent condensation seen with activity, thus suggesting that activity normally participates as a "helper factor," even though it is not strictly required. Since the formation of discrete patches during regeneration provides a sensitive measure of activity-dependent refinement, this was used to further address two controversial questions concerning the role of impulse activity. One is whether there is a chronologically defined critical period for activity-dependent refinement. This was tested by blocking impulse activity for 2 to 4 months, much longer than the activity-dependent refinement is thought to last, and then permitting activity to resume. We found that multiple patches were formed following this period of late activity, thus indicating that synaptic plasticity extends for several months beyond the supposed critical period. The other question was whether spontaneous retinal activity was sufficient for activity-dependent ordering. To test this, fish were kept in constant darkness during optic nerve crush and labelled with retinal spot injections at various times during regeneration. Condensation of label with the final formation of multiple patches formed at about the same time as fish with normal visual experience. This implies that the amount and extent of correlation of spontaneous activity in retina is adequate for driving activity-dependent refinement.}, Address = {Department of Developmental and Cell Biology, University of California, Irvine 92717.}, Author = {Olson, M D and Meyer, R L}, Crdt = {1991/01/15 00:00}, Da = {19910501}, Date = {1991 Jan 15}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {19910501}, Edat = {1991/01/15}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Darkness; Goldfish/*anatomy \& histology; Nerve Crush; Nerve Regeneration; Optic Nerve/physiology; Optic Nerve Injuries; Retinal Ganglion Cells/*drug effects/radiation effects/ultrastructure; Sensory Deprivation/physiology; Superior Colliculi/drug effects/radiation effects/*ultrastructure; Tetrodotoxin/*pharmacology; Visual Pathways/drug effects/radiation effects}, Mhda = {1991/01/15 00:01}, Month = {Jan}, Number = {3}, Own = {NLM}, Pages = {412--423}, Pl = {UNITED STATES}, pmid = {2007657}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Source = {J Comp Neurol. 1991 Jan 15;303(3):412-23.}, Status = {MEDLINE}, Title = {The effect of TTX-activity blockade and total darkness on the formation of retinotopy in the goldfish retinotectal projection}, Volume = {303}, Year = {1991}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903030307}} @article{Berson:1991, Abstract = {We have investigated the cellular localization of opioid peptides and binding sites in the cat's superior colliculus by testing the effects of retinal deafferentation and intracollicular excitotoxin lesions on patterns of enkephalin-like immunostaining and opiate receptor ligand binding. In normal cats, enkephalin-like immunoreactivity marks a thin tier in the most dorsal stratum griseum superficiale, small neurons of the stratum griseum superficiale, and patches of fibers in the intermediate and deeper gray layers. Eliminating crossed retinotectal afferents by contralateral eye enucleation had little immediate effect on this pattern, although chronic eye enucleation from birth did reduce immunoreactivity in the superficial layers. By contrast, fiber-sparing destruction of collicular neurons by the excitotoxins N-methyl-D-aspartate and ibotenic acid virtually eliminated enkephalin-like immunoreactivity in the neuropil of the upper stratum griseum superficiale, presumably by killing enkephalinergic cells of the superficial layers. Such lesions did not eliminate the patches of enkephalin-like immunoreactivity in the deeper layers. In normal cats, opiate receptor ligand binding is dense in the stratum griseum superficiale, particularly in its upper tier, and moderately dense in the intermediate gray layer. Contralateral eye removal had no detectable effect on the binding pattern, but excitotoxin lesions of the colliculus dramatically reduced binding in both superficial and deep layers. Some ligand binding, including part of that in the upper stratum griseum superficiale, apparently survived such lesions. Similar effects were observed in the lateral geniculate nucleus: enucleation produced no change in binding, whereas excitotoxin lesions greatly reduced specific opiate binding. We conclude that in the superficial collicular layers, both enkephalin-like opioid peptides and their membrane receptors are largely expressed by neurons of intrinsic collicular origin. The close correspondence between the location of these intrinsic opioid elements and the tier of retinal afferents terminating in the upper stratum griseum superficiale further suggests that opiatergic interneurons may modulate retinotectal transmission postsynaptically.}, Address = {Division of Biology and Medicine, Brown University, Providence, RI 02912.}, Author = {Berson, D M and Graybiel, A M and Bowen, W D and Thompson, L A}, Crdt = {1991/01/01 00:00}, Da = {19911113}, Date = {1991}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {19911113}, Edat = {1991/01/01}, Gr = {DA03776/DA/NIDA NIH HHS/United States; EY02866/EY/NEI NIH HHS/United States; EY06108/EY/NEI NIH HHS/United States}, Issn = {0306-4522 (Print)}, Jid = {7605074}, Journal = {Neuroscience}, Jt = {Neuroscience}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Autoradiography; Binding Sites; Cats; Enkephalins/*metabolism; Eye Enucleation; Immunohistochemistry; Neurotoxins/pharmacology; Superior Colliculi/drug effects/*metabolism}, Mhda = {1991/01/01 00:01}, Number = {2-3}, Own = {NLM}, Pages = {513--529}, Pii = {0306-4522(91)90312-C}, Pl = {ENGLAND}, pmid = {1922782}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Enkephalins); 0 (Neurotoxins)}, Sb = {IM}, Source = {Neuroscience. 1991;43(2-3):513-29.}, Status = {MEDLINE}, Title = {Evidence for intrinsic expression of enkephalin-like immunoreactivity and opioid binding sites in cat superior colliculus}, Volume = {43}, Year = {1991}} @article{Illing:1990, Abstract = {Parvalbumin-like immunoreactivity (PA-LI) has been studied in sections of the superior colliculus (SC) of the rat and its distribution compared to the patterns of acetylcholinesterase (AChE) and cytochrome oxidase (CO) staining. In the intermediate layers it was found that PA-LI is spatially associated with AChE only in the medial part of the SC, but assumes a complementary distribution further laterally. There was a positive correlation between PA-LI and CO. We conclude that the patterns of PA-LI and CO are not systematically related to collicular input known to be associated with the AChE-rich zones, but may reflect adherence to channel separation beyond the terminal fields of clustered afferents.}, Address = {Unit for Morphological Brain Research, Universitats-HNO-Klinik, Freiburg, F.R.G.}, Author = {Illing, R B and Vogt, D M and Spatz, W B}, Crdt = {1990/12/11 00:00}, Da = {19910409}, Date = {1990 Dec 11}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {19910409}, Edat = {1990/12/11}, Issn = {0304-3940 (Print)}, Jid = {7600130}, Journal = {Neurosci Lett}, Jt = {Neuroscience letters}, Language = {eng}, Lr = {20071115}, Mh = {Acetylcholinesterase/*analysis; Animals; Antibodies, Monoclonal/diagnostic use; Electron Transport Complex IV/*analysis; Immunohistochemistry; Parvalbumins/*analysis; Rats; Superior Colliculi/*cytology/enzymology}, Mhda = {1990/12/11 00:01}, Month = {Dec}, Number = {2}, Own = {NLM}, Pages = {197--200}, Pii = {0304-3940(90)90037-A}, Pl = {NETHERLANDS}, pmid = {1963482}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Antibodies, Monoclonal); 0 (Parvalbumins); EC 1.9.3.1 (Electron Transport Complex IV); EC 3.1.1.7 (Acetylcholinesterase)}, Sb = {IM}, Source = {Neurosci Lett. 1990 Dec 11;120(2):197-200.}, Status = {MEDLINE}, Title = {Parvalbumin in rat superior colliculus}, Volume = {120}, Year = {1990}} @article{Brecha:1987, Abstract = {Retinal ganglion cells are the projection neurons that link the retina to the brain. Peptide immunoreactive cells in the ganglion cell layer (GCL) of the mammalian retina have been noted but their identity has not been determined. We now report that, in the rabbit, 25-35% of all retinal ganglion cells contain substance P-like (SP) immunoreactivity. They were identified by either retrograde transport of fluorescent tracers injected into the superior colliculus, or by retrograde degeneration after optic nerve section. SP immunoreactive cells are present in all parts of the retina and have medium to large cell bodies with dendrites that ramify extensively in the proximal inner plexiform layer. Their axons terminate in the dorsal lateral geniculate nucleus, superior colliculus and accessory optic nuclei, and these terminals disappear completely after contralateral optic nerve section and/or eye enucleation. In the dorsal lateral geniculate nucleus large, beaded, immunoreactive axons and varicosities make up a narrow plexus just below the optic tract, where they define a new geniculate lamina. The varicosities make multiple synaptic contacts with dendrites of dorsal lateral geniculate nucleus projection neurons and presumptive interneurons in complex glomerular neuropil. This is direct evidence that some mammalian retinal ganglion cells contain substance P-like peptides and strongly suggests that, in the rabbit, substance P (or related tachykinins) may be a transmitter or modulator in a specific population or populations of retinal ganglion cells.}, Author = {Brecha, N and Johnson, D and Bolz, J and Sharma, S and Parnavelas, J G and Lieberman, A R}, Crdt = {1987/05/14 00:00}, Da = {19870615}, Date = {1987 May 14-20}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {19870615}, Edat = {1987/05/14}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Axons/*ultrastructure; Dendrites/ultrastructure; Histocytochemistry; Immunologic Tests; Microscopy, Electron; Nerve Endings/*ultrastructure; Neural Pathways/ultrastructure; Optic Nerve/physiology; Rabbits; Retina/*ultrastructure; Retinal Ganglion Cells/metabolism/*ultrastructure; Substance P/*metabolism}, Mhda = {1987/05/14 00:01}, Month = {May}, Number = {6118}, Own = {NLM}, Pages = {155--158}, Pl = {ENGLAND}, pmid = {2437459}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {33507-63-0 (Substance P)}, Sb = {IM}, Source = {Nature. 1987 May 14-20;327(6118):155-8.}, Status = {MEDLINE}, Title = {Substance P-immunoreactive retinal ganglion cells and their central axon terminals in the rabbit}, Volume = {327}, Year = {1987}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/327155a0}} @article{Edwards:1986, Abstract = {The emergence of laminar organization in the superior colliculus was investigated in the mouse with several anatomical methods, including tritiated-thymidine autoradiography, Golgi impregnation, and general stains for cell bodies and for fibers. The sequence of neurogenesis, cell migration, and early morphological differentiation of neurons was shown to exhibit a discontinuity between the lower and upper divisions (i.e., between the deep and intermediate "gray" and "white" layers and the superficial "gray" and "white" layers). These events proceed in an inside-out order within the lower division, but the same events within the upper division commence in advance of the completion of this progression. Thus, peak generation times for layers of the lower division proceed from (embryonic day) E11 to E13 and for the upper division from E12 to E13. Cell migration, as monitored with tritiated-thymidine labelling, reflects closely the pattern of cytogenesis. This is most clearly evident on E15 when a population of E11-labelled cells is divided into superficial and deep layers (the strata superficiale and profundum--SS and SP) by the interposition of E13-labelled cells at an intermediate level (stratum intermedium--SI). A contingent of the latter cells continue their migration and join their predecessors within the SS on E17, a time point when cell migrations are largely complete. Paralleling this sequence of arrival of neurons and the formation of three primary layers, both the time course of accumulation of fiber fascicles and the early morphological differentiation of neurons in the interval from E13 to E17 tends to proceed from SP to SS and from SS to SI. Thus, the transverse fiber system and large multipolar neurons of SP develop in advance of the longitudinal fiber system and vertically oriented neurons of SS, which in turn develop precociously with respect to the longitudinal fibers and medium-sized multipolar neurons of SI. In contrast, later events of differentiation that underly a major radial growth and an architectonic sublamination of the primary strata proceed in a simpler inside-out sequence from E17 to (postnatal day) P6. The major morphogenetic events underlying the establishment of statification in the colliculus appear to involve the operation of relatively independent programs of assembly for the two basic subdivisions. It is probable that selective cell-cell interactions contribute to the delivery of concurrently generated neurons to different laminae as well as to the deployment of axons in a manner that respects laminar boundaries.}, Author = {Edwards, M A and Caviness, V S Jr and Schneider, G E}, Crdt = {1986/06/15 00:00}, Da = {19860820}, Date = {1986 Jun 15}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {19860820}, Edat = {1986/06/15}, Issn = {0021-9967 (Print)}, Jid = {0406041}, Journal = {J Comp Neurol}, Jt = {The Journal of comparative neurology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Cell Differentiation; Cell Movement; Hybridization, Genetic; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mitosis; Morphogenesis; Neurons/cytology; Superior Colliculi/cytology/embryology/*growth \& development}, Mhda = {2001/03/28 10:01}, Month = {Jun}, Number = {3}, Own = {NLM}, Pages = {395--409}, Pl = {UNITED STATES}, pmid = {3722463}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Source = {J Comp Neurol. 1986 Jun 15;248(3):395-409.}, Status = {MEDLINE}, Title = {Development of cell and fiber lamination in the mouse superior colliculus}, Volume = {248}, Year = {1986}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902480308}} @article{Tumosa:1986, Abstract = {We have demonstrated that a significant fraction of cells in layer 1 of goldfish optic tectum are immunoreactive for choline acetyltransferase. These cells constitute 4-7% of type XIV cells, which are thought to be intrinsic neurons and represent 95% of all tectal cells. The number of immunoreactive type XIV cells is unchanged following short-term enucleation. The possible integrative role of these putative cholinergic neurons is discussed in relation to sensory functions of the optic tectum.}, Author = {Tumosa, N and Stell, W K and Johnson, C D and Epstein, M L}, Crdt = {1986/04/09 00:00}, Da = {19860627}, Date = {1986 Apr 9}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {19860627}, Edat = {1986/04/09}, Issn = {0006-8993 (Print)}, Jid = {0045503}, Journal = {Brain Res}, Jt = {Brain research}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Choline O-Acetyltransferase/*analysis; Goldfish; Neurons/cytology/enzymology/*physiology; Superior Colliculi/cytology/enzymology/*physiology}, Mhda = {1986/04/09 00:01}, Month = {Apr}, Number = {2}, Own = {NLM}, Pages = {365--369}, Pii = {0006-8993(86)90495-6}, Pl = {NETHERLANDS}, pmid = {3708332}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {EC 2.3.1.6 (Choline O-Acetyltransferase)}, Sb = {IM}, Source = {Brain Res. 1986 Apr 9;370(2):365-9.}, Status = {MEDLINE}, Title = {Putative cholinergic interneurons in the optic tectum of goldfish}, Volume = {370}, Year = {1986}} @article{So:1985, Abstract = {The synaptic organization of the alpha sector of the dorsal lateral geniculate nucleus has been examined by electron microscopy in normal adult hamsters and in adult hamsters subjected to unilateral eye enucleation or intravitreal injection of horseradish peroxidase. Two types of neuropil are apparent. Islands of complex neuropil partially enclosed by astrocyte processes (synaptic glomeruli) are surrounded by a sea of simpler non-glomerular neuropil. The latter is dominated by small axon terminals with spherical synaptic vesicles and Gray type 1 axodendritic contacts (SR-boutons) and also contains axon terminals with flattened synaptic vesicles (F-boutons). The glomerular neuropil contains exclusively postsynaptic dendrites and dendritic protrusions of presumptive projection cells; pre- and postsynaptic pleomorphic-vesicle-containing P-boutons (interpreted as appendages of the dendrites of interneurons); large axon terminals containing spherical synaptic vesicles and large pale mitochondria (R-boutons) which were experimentally identified as retinal terminals and which are presynaptic to both projection cell dendrites and P-boutons at Gray type 1 contacts; F-boutons (minority component). F-boutons and P-boutons are presynaptic to both projection cell dendrites and P-boutons and P-boutons are the intermediate elements of various serial synapses including triplet (triadic) synapses. Medium-large terminals with spherical synaptic vesicles and dark mitochondria (RLD-boutons) which were commonly invaginated by dendritic spines of projection cells in small glomerulus-like formations were also identified. The origin of RLD-boutons is unknown but SR-boutons probably derive chiefly from ipsilateral visual cortex and possibly also from superior colliculus, and non-glomerular F-boutons probably originate in the ipsilateral thalamic reticular nucleus. No differences in synaptic organization were found between the part of the nucleus which receives uncrossed retinal input and the part which receives crossed input, nor were differences seen in the size, fine structure or relationships between the terminals of identified crossed and uncrossed retinal axons.}, Author = {So, K F and Campbell, G and Lieberman, A R}, Crdt = {1985/01/01 00:00}, Da = {19850515}, Date = {1985}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {19850515}, Edat = {1985/01/01}, Issn = {0340-2061 (Print)}, Jid = {7505194}, Journal = {Anat Embryol (Berl)}, Jt = {Anatomy and embryology}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Cricetinae/*anatomy \& histology; Geniculate Bodies/*ultrastructure; Horseradish Peroxidase/diagnostic use; Injections; Mesocricetus; Microscopy, Electron; Nerve Degeneration; Nerve Endings/ultrastructure; Neurons/ultrastructure; Retina/ultrastructure; Synapses/*ultrastructure; Vitreous Body}, Mhda = {1985/01/01 00:01}, Number = {2}, Own = {NLM}, Pages = {223--234}, Pl = {GERMANY, WEST}, pmid = {3985371}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {EC 1.11.1.- (Horseradish Peroxidase)}, Sb = {IM}, Source = {Anat Embryol (Berl). 1985;171(2):223-34.}, Status = {MEDLINE}, Title = {Synaptic organization of the dorsal lateral geniculate nucleus in the adult hamster. An electron microscope study using degeneration and horseradish peroxidase tracing techniques}, Volume = {171}, Year = {1985}} @article{Altman:1981, Abstract = {Groups of pregnant rats were injected with two successive daily doses of 3H-thymidine from gestational day 12 and 13 (E12 + E13) until the day before parturition (E21 + 22) in order to label all the multiplying precursors of neurons. At 60 days of age the proportion of neurons generated (or no longer labelled) on specific days was determined in the separate layers of the superiorr colliculus. Neurogenesis begins with layers V and IV on day E12; the bulk (87%) of these cells are generated on day E13. This early-produced band of large neurons, the intermediate magnocellular zone, divides the superior colliculus into two cytogenetically distinct regions. In both the deep and the superficial superior colliculus neuron production is relatively protracted. In the deep superior colliculus neuron production peaks on day E15 in lay VII, on day E15 and E16 in lay VI, and on day E16 (the large neurons excluded) in layer V, indicating an inside-out sequence. In the superficial superio coliculus peak production time of both layer I and II is on day E16 but in the latter region neuron production is more prolonged and ends on day E18. One interpretation of these results is that the two pairs of superficial layers are produced in an outside-in sequence. These three cytogenetic subdivisions of the superior colliculus may be correlated with its structural-functional parcellation into an efferent spinotectal, a deep somatomotor and a superficial visual component. A comparison of neurogenesis in different components of the visuomotor and visual pathways of the rat indicates that the motor neurons of the extraocular muscles, the abducens, trochlear and oculomotor nuclei, and neurons of the nucleus of Darkschewitsch are produced first. Next in line are source neurons of efferents to the bulb and the spinal cord: those of the Edinger-Westphal nucleus and the intermediate magnocellular zone of the superior colliculus. These are followed by the relay neurons of the dorsal nucleus of the lateral geniculate body. The neurons of the superficial superior colliculus and of the visual cortex implicated in visual sensori-motor integrations are produced last.}, Author = {Altman, J and Bayer, S A}, Crdt = {1981/01/01 00:00}, Da = {19810810}, Date = {1981}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:42:44 -0400}, Dcom = {19810810}, Edat = {1981/01/01}, Issn = {0014-4819 (Print)}, Jid = {0043312}, Journal = {Exp Brain Res}, Jt = {Experimental brain research. Experimentelle Hirnforschung. Experimentation cerebrale}, Language = {eng}, Lr = {20080215}, Mh = {Afferent Pathways/embryology/physiology; Animals; Female; Neurons/*physiology; Pregnancy; Rats; Superior Colliculi/cytology/*embryology/physiology; Visual Pathways/cytology/*embryology/physiology}, Mhda = {1981/01/01 00:01}, Number = {3-4}, Own = {NLM}, Pages = {424--434}, Pl = {GERMANY, WEST}, pmid = {7238681}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Exp Brain Res. 1981;42(3-4):424-34.}, Status = {MEDLINE}, Title = {Time of origin of neurons of the rat superior colliculus in relation to other components of the visual and visuomotor pathways}, Volume = {42}, Year = {1981}} @article{Mathers:1979, Abstract = {To further study the existence of a critical trophic period in the development of the chick optic tectum, during which the presence of retinal synapses is essential to the continued growth of tectal neurons, we have unilaterally enucleated embryos between stages 14--20 and allowed survival until stages 35--43. If the critical trophic period is between stages 40--44, as previously reported, then we reasoned that early removal of the eye might not have any effect on tectal development until the critical period. We assessed tectal neuron survival by staining for degeneration in the efferent projections of tectal neurons. In early enucleates, degeneration was present from stages 37--43, and the severity of the degeneration was much reduced in comparison to animals enucleated during the critical period. These findings substantiate the proposition that there is a critical period late in chick tectal development. However, because the degeneration in tectal projections is less intense than in animals enucleated during the critical period, we suggest that the early enucleation has permitted axons from the remaining eye to be routed to the deafferented tectum, where they may help to sustain a portion of the tectal neurons through the critical period. Moreover, the somewhat earlier appearance of degeneration in tectal efferent pathways of early enucleates suggests that a subtle trophic relationship between retina and tectum may exist prior to stage 40, even though this relationship is not revealed when enucleations are performed later, as between stages 35--40 (ref. 17).}, Author = {Mathers, L H Jr and Ostrach, L H}, Crdt = {1979/07/13 00:00}, Da = {19791017}, Date = {1979 Jul 13}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-03-26 12:44:25 -0400}, Dcom = {19791017}, Edat = {1979/07/13}, Issn = {0006-8993 (Print)}, Jid = {0045503}, Journal = {Brain Res}, Jt = {Brain research}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Age Factors; Animals; Axons/ultrastructure; *Cell Differentiation; Chick Embryo; Diencephalon/cytology; Dominance, Cerebral/physiology; Efferent Pathways/cytology; Interneurons/cytology; Mesencephalon/cytology; Nerve Degeneration; Neurons/cytology; Retina/*cytology; Sensory Deprivation; Superior Colliculi/*cytology; Synapses/ultrastructure; Visual Pathways/cytology}, Mhda = {2001/03/28 10:01}, Month = {Jul}, Number = {2}, Own = {NLM}, Pages = {219--230}, Pii = {0006-8993(79)90103-3}, Pl = {NETHERLANDS}, pmid = {466408}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Brain Res. 1979 Jul 13;170(2):219-30.}, Status = {MEDLINE}, Title = {A critical period in the development of tectal neurons in the chick, as revealed by early enucleation}, Volume = {170}, Year = {1979}} @article{Leibnitz:1979, Abstract = {12 adult white lab-rats were enucleated and after a survival period of 1, 3, 7 and 30 days the activities of GABA-T, GDH, LDH, SDH and GPDH were demonstrated histochemically in the Tractus opticus (To), Corpus geniculatum laterale, pars dorsalis (CGLd) et ventralis (CGLv), Colliculus superior (Cs) and Nucleus olivaris praetectalis (Nop). Since the ipsi- and contralateral grisea are always in the same tissue section the enzyme activities can be quantitatively compared by visual impression without a greater mistake. In To enucleation caused a hypertrophy of astrocytes together with an increase of the activities of GABA-T, GDH, LDH, and GPDH in these cells. The reactions indicate a more intensive metabolism in connection with the myelin degradation. In CGLd, CGLv, Cs and Nop following enucleation there appeared contralaterally a graded loss in the activities of GDH, LDH, GPDH, and GABA-T; only SDH scarely changed its activity. The fastest and strongest reaction was found in Cs and Nop, while CGLd and CGLv reacted later and to a less degree. In CGLv the enzyme reaction was limited to the lateral part of the nucleus. As diminution of activity is caused by degeneration of the retinal terminals the effected enzymes must be localised in cytoplasma and mitochondria of these terminals. Taking into account findings from literature the following is concluded from the time patterns, the degree of diminution of the enzyme activities and the relation of retinal to extraretinal terminals in the individual nuclei: GABA probably acts as a transmitter in interneurons of CGLd, Cs, and Nop. Glutamate is a transmitter in Cs and Nop.}, Author = {Leibnitz, L and Bar, B}, Crdt = {1979/01/01 00:00}, Da = {19800825}, Date = {1979}, Date-Added = {2009-03-26 12:42:43 -0400}, Date-Modified = {2009-07-30 11:33:45 -0400}, Dcom = {19800825}, Edat = {1979/01/01}, Issn = {0021-8359 (Print)}, Jid = {0421521}, Journal = {J Hirnforsch}, Jt = {Journal fur Hirnforschung}, Language = {ger}, Lr = {20071115}, Mh = {4-Aminobutyrate Transaminase/metabolism; Animals; Dominance, Cerebral/physiology; Geniculate Bodies/enzymology; Glutamate Dehydrogenase/metabolism; Glycerolphosphate Dehydrogenase/metabolism; L-Lactate Dehydrogenase/metabolism; Male; Optic Nerve/enzymology; Rats; Retina/*enzymology; *Sensory Deprivation; Succinate Dehydrogenase/metabolism; Superior Colliculi/enzymology; Thalamic Nuclei/enzymology; Visual Cortex/enzymology; Visual Pathways/*enzymology}, Mhda = {1979/01/01 00:01}, Number = {6}, Own = {NLM}, Pages = {637--649}, Pl = {GERMANY, EAST}, pmid = {121134}, Pst = {ppublish}, Pt = {English Abstract; Journal Article}, Rn = {EC 1.1.- (Glycerolphosphate Dehydrogenase); EC 1.1.1.27 (L-Lactate Dehydrogenase); EC 1.3.99.1 (Succinate Dehydrogenase); EC 1.4.1.2 (Glutamate Dehydrogenase); EC 2.6.1.19 (4-Aminobutyrate Transaminase)}, Sb = {IM}, Status = {MEDLINE}, Title = {[Enzyme histochemical examinations of the visual system of the adult rat following unilateral enucleation]}, Tt = {Enzymhistochemische Untersuchungen am visuellen System der adulten Ratte nach unilateraler Enucleation.}, Volume = {20}, Year = {1979}} @article{Hubel:1959a, Author = {Hubel, D H}, Crdt = {1959/09/02 00:00}, Da = {19601201}, Date = {1959 Sep 2}, Date-Added = {2009-03-26 12:19:51 -0400}, Date-Modified = {2016-01-13 18:17:21 +0000}, Dcom = {19981101}, Edat = {1959/09/02}, Issn = {0022-3751 (Print)}, Jid = {0266262}, Journal = {J Physiol}, Jt = {The Journal of physiology}, Keywords = {*CEREBRAL CORTEX/physiology; *NEURONS/physiology; 21 Neurophysiology}, Language = {eng}, Lr = {20081120}, Mh = {Cerebral Cortex/*physiology; Neurons/*physiology}, Mhda = {1959/09/02 00:01}, Month = {Sep}, Oid = {NLM: PMC1357023}, Oto = {NLM}, Own = {NLM}, Pages = {226--238}, Pl = {Not Available}, Pmc = {PMC1357023}, pmid = {14403678}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {OM}, Status = {MEDLINE}, Title = {Single unit activity in striate cortex of unrestrained cats}, Volume = {147}, Year = {1959}} @article{Hubel:1959, Author = {Hubel, D H and Wiesel, T N}, Crdt = {1959/10/01 00:00}, Da = {19601201}, Date = {1959 Oct}, Date-Added = {2009-03-26 12:19:42 -0400}, Date-Modified = {2016-01-13 18:17:10 +0000}, Dcom = {19981101}, Edat = {1959/10/01}, Issn = {0022-3751 (Print)}, Jid = {0266262}, Journal = {J Physiol}, Jt = {The Journal of physiology}, Keywords = {*CEREBRAL CORTEX/physiology; *NEURONS/physiology; 21 Neurophysiology}, Language = {eng}, Lr = {20081120}, Mh = {Cerebral Cortex/*physiology; Neurons/*physiology}, Mhda = {1959/10/01 00:01}, Month = {Oct}, Oid = {NLM: PMC1363130}, Oto = {NLM}, Own = {NLM}, Pages = {574--591}, Pl = {Not Available}, Pmc = {PMC1363130}, pmid = {14403679}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {OM}, Source = {J Physiol. 1959 Oct;148:574-91.}, Status = {MEDLINE}, Title = {Receptive fields of single neurones in the cat's striate cortex}, Volume = {148}, Year = {1959}, url = {papers/HUBEL_JPhysiol1959.pdf}} @article{Ramocki:2008, Abstract = {Failure of normal brain development leads to mental retardation or autism in about 3% of children. Many genes integral to pathways by which synaptic modification and the remodelling of neuronal networks mediate cognitive and social development have been identified, usually through loss of function. Evidence is accumulating, however, that either loss or gain of molecular functions can be deleterious to the nervous system. Copy-number variation, regulation of gene expression by non-coding RNAs and epigenetic changes are all mechanisms by which altered gene dosage can cause the failure of neuronal homeostasis.}, Address = {Department of Pediatrics, Section of Pediatric Neurology and Developmental Neuroscience, Baylor College of Medicine, 1 Baylor Plaza, MS 225, BCMT-T807, Houston, Texas 77030, USA. mramocki@bcm.tmc.edu}, Author = {Ramocki, Melissa B and Zoghbi, Huda Y}, Crdt = {2008/10/17 09:00}, Da = {20081016}, Date = {2008 Oct 16}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081118}, Edat = {2008/10/17 09:00}, Gr = {1K08 NS062711-01/NS/NINDS NIH HHS/United States; 1R01 NS057819-01/NS/NINDS NIH HHS/United States; T32 NS43124/NS/NINDS NIH HHS/United States; Howard Hughes Medical Institute/United States}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Neurophysiology}, Language = {eng}, Mh = {Animals; Cytoskeleton/metabolism; *Gene Expression Regulation; *Homeostasis/genetics; Humans; Mental Disorders/*genetics/*physiopathology; Neurons/*metabolism; Synapses/metabolism}, Mhda = {2008/11/19 09:00}, Month = {Oct}, Number = {7215}, Own = {NLM}, Pages = {912--918}, Pii = {nature07457}, Pl = {England}, pmid = {18923513}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {69}, Sb = {IM}, Status = {MEDLINE}, Title = {Failure of neuronal homeostasis results in common neuropsychiatric phenotypes}, Volume = {455}, Year = {2008}, url = {papers/Ramocki_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07457}} @article{Sato:2008, Abstract = {Sensory experience profoundly shapes neural circuitry of juvenile brain. Although the visual cortex of adult rodents retains a capacity for plasticity in response to monocular visual deprivation, the nature of this plasticity and the neural circuit changes that accompany it remain enigmatic. Here, we investigate differences between adult and juvenile ocular dominance plasticity using Fourier optical imaging of intrinsic signals in mouse visual cortex. This comparison reveals that adult plasticity takes longer than in the juvenile mouse, is of smaller magnitude, has a greater contribution from the increase in response to the open eye, and has less effect on the hemisphere ipsilateral to the deprived eye. Binocular deprivation also causes different changes in the adult. Adult plasticity is similar to juvenile plasticity in its dependence on signaling through NMDA receptors. We propose that adult ocular dominance plasticity arises from compensatory mechanisms that counterbalance the loss of afferent activity caused by visual deprivation.}, Address = {Department of Physiology, W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, California 94143-0444, USA.}, Author = {Sato, Masaaki and Stryker, Michael P}, Crdt = {2008/10/10 09:00}, Da = {20081009}, Date = {2008 Oct 8}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081103}, Edat = {2008/10/10 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology}, Language = {eng}, Mh = {Adaptation, Physiological; Aging/physiology; Animals; *Critical Period (Psychology); Dominance, Ocular/*physiology; Mice; Mice, Inbred C57BL; Neuronal Plasticity/*physiology; Receptors, N-Methyl-D-Aspartate/metabolism; Sensory Deprivation/physiology; Signal Transduction/physiology; Time Factors; Vision, Binocular; Vision, Monocular; Visual Cortex/*physiology}, Mhda = {2008/11/04 09:00}, Month = {Oct}, Number = {41}, Own = {NLM}, Pages = {10278--10286}, Pii = {28/41/10278}, Pl = {United States}, pmid = {18842887}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Receptors, N-Methyl-D-Aspartate)}, Sb = {IM}, Status = {MEDLINE}, Title = {Distinctive features of adult ocular dominance plasticity}, Volume = {28}, Year = {2008}, url = {papers/Sato_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2451-08.2008}} @article{Dean:1989, Abstract = {Recent studies of the effects of stimulating the superior colliculus (SC) in rodents suggest that this structure mediates at least two classes of response to novel sensory stimuli. One class contains the familiar orienting response, together with movements resembling tracking or pursuit, and appears appropriate for undefined sensory 'events'. The second class contains defensive movements such as avoidance or flight, together with cardiovascular changes, that would be appropriate for a sudden emergency such as the appearance of a predator, or of an object on collision course. The two response systems appear to depend on separate output projections, and are probably subject to different sensory and forebrain influences. These findings (1) suggest an explanation for the complex anatomical organization of the SC, with multiple output pathways differentially accessed by a very wide variety of inputs, (2) emphasize the similarities between the SC and the optic tectum in non-mammalian species, and (3) suggest that the SC may be useful as a model for studying both the sensory control of defensive responses, and how intelligent decisions can be taken about relatively simple sensory inputs.}, Author = {Dean, P and Redgrave, P and Westby, G W}, Crdt = {1989/04/01 00:00}, Da = {19890615}, Date = {1989 Apr}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2009-03-26 12:10:11 -0400}, Dcom = {19890615}, Edat = {1989/04/01}, Issn = {0166-2236 (Print)}, Jid = {7808616}, Journal = {Trends Neurosci}, Jt = {Trends in neurosciences}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Behavior, Animal/*physiology; Cardiovascular Physiological Phenomena; Orientation/*physiology; Superior Colliculi/*physiology}, Mhda = {1989/04/01 00:01}, Month = {Apr}, Number = {4}, Own = {NLM}, Pages = {137--147}, Pii = {0166-2236(89)90052-0}, Pl = {ENGLAND}, pmid = {2470171}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {66}, Sb = {IM}, Status = {MEDLINE}, Title = {Event or emergency? Two response systems in the mammalian superior colliculus}, Volume = {12}, Year = {1989}, url = {papers/Dean_TrendsNeurosci1989.pdf}} @article{Sato:2007b, Abstract = {Cortical maps, consisting of orderly arrangements of functional columns, are a hallmark of the organization of the cerebral cortex. However, the microorganization of cortical maps at the level of single neurons is not known, mainly because of the limitations of available mapping techniques. Here, we used bulk loading of Ca(2+) indicators combined with two-photon microscopy to image the activity of multiple single neurons in layer (L) 2/3 of the mouse barrel cortex in vivo. We developed methods that reliably detect single action potentials in approximately half of the imaged neurons in L2/3. This allowed us to measure the spiking probability following whisker deflection and thus map the whisker selectivity for multiple neurons with known spatial relationships. At the level of neuronal populations, the whisker map varied smoothly across the surface of the cortex, within and between the barrels. However, the whisker selectivity of individual neurons recorded simultaneously differed greatly, even for nearest neighbors. Trial-to-trial correlations between pairs of neurons were high over distances spanning multiple cortical columns. Our data suggest that the response properties of individual neurons are shaped by highly specific subcolumnar circuits and the momentary intrinsic state of the neocortex.}, Author = {Sato, TR and Gray, NW and Mainen, ZF and Svoboda, K}, Crdt = {2007/07/12 09:00}, Da = {20070719}, Date = {2007 Jul 10}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dep = {20070710}, Edat = {2007/07/12 09:00}, Issn = {1545-7885 (Electronic)}, Jid = {101183755}, Journal = {PLoS Biol}, Jt = {PLoS biology}, Keywords = {21 Neurophysiology;calcium imaging;optical physiology;optical imaging;microscopy;Multiphoton;mice;mouse;Somatosensory Cortex;21 Circuit structure-function;connectivity;network;Technique}, Language = {ENG}, Mhda = {2007/07/12 09:00}, Month = {Jul}, Number = {7}, Own = {NLM}, Pages = {e189}, Phst = {2006/12/12 {$[$}received{$]$}; 2007/05/15 {$[$}accepted{$]$}}, Pii = {06-PLBI-RA-2351}, Pmc = {PMC1914403}, pmid = {17622195}, Pst = {aheadofprint}, Pt = {JOURNAL ARTICLE}, Status = {Publisher}, Title = {The Functional Microarchitecture of the Mouse Barrel Cortex}, Volume = {5}, Year = {2007}, url = {papers/Sato_PLoSBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0050189}} @article{McLaughlin:2003, Abstract = {During retinocollicular map development, spontaneous waves of action potentials spread across the retina, correlating activity among neighboring retinal ganglion cells (RGCs). To address the role of retinal waves in topographic map development, we examined wave dynamics and retinocollicular projections in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor. beta2(-/-) mice lack waves during the first postnatal week, but RGCs have high levels of uncorrelated firing. By P8, the wild-type retinocollicular projection remodels into a refined map characterized by axons of neighboring RGCs forming focal termination zones (TZs) of overlapping arbors. In contrast, in P8 beta2(-/-) mice, neighboring RGC axons form large TZs characterized by broadly distributed arbors. At P8, glutamatergic retinal waves appear in beta2(-/-) mice, and later, visually patterned activity appears, but the diffuse TZs fail to remodel. Thus, spontaneous retinal waves that correlate RGC activity are required for retinotopic map remodeling during a brief early critical period.}, Address = {Molecular Neurobiology Lab, The Salk Institute, La Jolla, CA 92037, USA.}, Author = {McLaughlin, Todd and Torborg, Christine L and Feller, Marla B and O'Leary, Dennis D M}, Cin = {Neuron. 2003 Dec 18;40(6):1053-5. PMID: 14687538}, Crdt = {2003/12/23 05:00}, Da = {20031222}, Date = {2003 Dec 18}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2013-05-29 15:12:54 +0000}, Dcom = {20040128}, Edat = {2003/12/23 05:00}, Gr = {R01 EY07025/EY/NEI NIH HHS/United States; R01 EY13528/EY/NEI NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development; retinal waves; Retinal Ganglion Cells; superior colliculus; nicotinic; Acetylcholine; Receptor; mice; mouse; transgenic; activity manipulation; development; visual system; optic tectum; connectivity; tracer; currOpinRvw}, Language = {eng}, Lr = {20071115}, Mh = {Action Potentials/*physiology; Animals; Animals, Newborn; Mice; Mice, Knockout; Neural Pathways/growth \& development/metabolism; Receptors, Nicotinic/deficiency/genetics; Retina/*growth \& development/metabolism; Retinal Ganglion Cells/physiology; Superior Colliculi/*growth \& development/metabolism; Time Factors}, Mhda = {2004/01/30 05:00}, Month = {Dec}, Number = {6}, Own = {NLM}, Pages = {1147-1160}, Pii = {S0896627303007906}, Pl = {United States}, pmid = {14687549}, Pst = {ppublish}, Pt = {Comparative Study; In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Receptors, Nicotinic); 0 (nicotinic receptor beta2)}, Sb = {IM}, Status = {MEDLINE}, Title = {Retinotopic map refinement requires spontaneous retinal waves during a brief critical period of development}, Volume = {40}, Year = {2003}, url = {papers/McLaughlin_Neuron2003.pdf}} @article{Yu:2009, Abstract = {Neurons in the mammalian neocortex are organized into functional columns. Within a column, highly specific synaptic connections are formed to ensure that similar physiological properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly specific to allow even adjacent neurons to convey information independently. How this fine-scale microcircuit is constructed to create a functional columnar architecture at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by in utero intraventricular injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex.}, Address = {Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue.}, Author = {Yu, YC and Bultje, RS and Wang, X and Shi, SH}, Crdt = {2009/02/11 09:00}, Da = {20090210}, Date = {2009 Feb 8}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dep = {20090208}, Edat = {2009/02/11 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {10 Development; 21 Neurophysiology}, Language = {ENG}, Mhda = {2009/02/11 09:00}, Month = {Feb}, Own = {NLM}, Phst = {2008/10/22 {$[$}received{$]$}; 2008/12/11 {$[$}accepted{$]$}; 2009/02/08 {$[$}aheadofprint{$]$}}, Pii = {nature07722}, pmid = {19204731}, Pst = {aheadofprint}, Pt = {JOURNAL ARTICLE}, Status = {Publisher}, Title = {Specific synapses develop preferentially among sister excitatory neurons in the neocortex}, Year = {2009}, url = {papers/Yu_Nature2009.pdf}, Bdsk-File-2 = {papers/Yu_Nature2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07722}} @article{Malone:2009, Abstract = {Transposons populate the landscape of all eukaryotic genomes. Often considered purely genomic parasites, transposons can also benefit their hosts, playing roles in gene regulation and in genome organization and evolution. Peaceful coexistence with mobile elements depends upon adaptive control mechanisms, since unchecked transposon activity can impact long-term fitness and acutely reduce the fertility of progeny. Here, we review the conserved roles played by small RNAs in the adaptation of eukaryotes to coexist with their genomic colonists. An understanding of transposon-defense pathways has uncovered recurring themes in the mechanisms by which genomes distinguish "self" from "non-self" and selectively silence the latter.}, Address = {Watson School of Biological Sciences, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.}, Author = {Malone, Colin D and Hannon, Gregory J}, Crdt = {2009/02/26 09:00}, Da = {20090225}, Date = {2009 Feb 20}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090305}, Edat = {2009/02/26 09:00}, Gr = {Howard Hughes Medical Institute/United States}, Issn = {1097-4172 (Electronic)}, Jid = {0413066}, Journal = {Cell}, Jt = {Cell}, Keywords = {15 ERVs retroelements}, Language = {eng}, Mh = {Animals; *Genome; *Genome, Human; Humans; Models, Biological; RNA, Untranslated/*genetics/*metabolism}, Mhda = {2009/03/06 09:00}, Month = {Feb}, Number = {4}, Own = {NLM}, Pages = {656--668}, Pii = {S0092-8674(09)00127-5}, Pl = {United States}, pmid = {19239887}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Review}, Rf = {160}, Rn = {0 (RNA, Untranslated)}, Sb = {IM}, Status = {MEDLINE}, Title = {Small RNAs as guardians of the genome}, Volume = {136}, Year = {2009}, url = {papers/Malone_Cell2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2009.01.045}} @article{Huang:2008, Abstract = {GABA-mediated synaptic inhibition is crucial in neural circuit operations. In mammalian brains, the development of inhibitory synapses and innervation patterns is often a prolonged postnatal process, regulated by neural activity. Emerging evidence indicates that gamma-aminobutyric acid (GABA) acts beyond inhibitory transmission and regulates inhibitory synapse development. Indeed, GABA(A) receptors not only function as chloride channels that regulate membrane voltage and conductance but also play structural roles in synapse maturation and stabilization. The link from GABA(A) receptors to postsynaptic and presynaptic adhesion is probably mediated, partly by neuroligin-reurexin interactions, which are potent in promoting GABAergic synapse formation. Therefore, similar to glutamate signaling at excitatory synapse, GABA signaling may coordinate maturation of presynaptic and postsynaptic sites at inhibitory synapses. Defining the many steps from GABA signaling to receptor trafficking/stability and neuroligin function will provide further mechanistic insights into activity-dependent development and possibly plasticity of inhibitory synapses.}, Address = {Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA. huangj@cshl.edu}, Author = {Huang, Z Josh and Scheiffele, Peter}, Crdt = {2008/06/03 09:00}, Da = {20080618}, Date = {2008 Feb}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Dcom = {20080930}, Dep = {20080529}, Edat = {2008/06/03 09:00}, Issn = {0959-4388 (Print)}, Jid = {9111376}, Journal = {Curr Opin Neurobiol}, Jt = {Current opinion in neurobiology}, Keywords = {21 Neurophysiology; 21 Activity-development; currOpinRvw}, Language = {eng}, Mh = {Animals; Brain/cytology/*embryology/*metabolism; Cell Adhesion/genetics; Cell Differentiation/genetics; Humans; Membrane Proteins/genetics/*metabolism; Nerve Tissue Proteins/genetics/*metabolism; Neural Inhibition/*physiology; Receptors, GABA-A/genetics/metabolism; Synapses/*metabolism; Synaptic Transmission/genetics; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2008/10/01 09:00}, Month = {Feb}, Number = {1}, Own = {NLM}, Pages = {77--83}, Phst = {2008/04/18 {$[$}received{$]$}; 2008/05/05 {$[$}revised{$]$}; 2008/05/08 {$[$}accepted{$]$}; 2008/05/29 {$[$}aheadofprint{$]$}}, Pii = {S0959-4388(08)00036-6}, Pl = {England}, pmid = {18513949}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {64}, Rn = {0 (Membrane Proteins); 0 (Nerve Tissue Proteins); 0 (Receptors, GABA-A); 0 (neuroligin 1); 56-12-2 (gamma-Aminobutyric Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {GABA and neuroligin signaling: linking synaptic activity and adhesion in inhibitory synapse development}, Volume = {18}, Year = {2008}, url = {papers/Huang_CurrOpinNeurobiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2008.05.008}} @article{Mank:2008, Abstract = {Neurons in the nervous system can change their functional properties over time. At present, there are no techniques that allow reliable monitoring of changes within identified neurons over repeated experimental sessions. We increased the signal strength of troponin C-based calcium biosensors in the low-calcium regime by mutagenesis and domain rearrangement within the troponin C calcium binding moiety to generate the indicator TN-XXL. Using in vivo two-photon ratiometric imaging, we show that TN-XXL exhibits enhanced fluorescence changes in neurons of flies and mice. TN-XXL could be used to obtain tuning curves of orientation-selective neurons in mouse visual cortex measured repeatedly over days and weeks. Thus, the genetically encoded calcium indicator TN-XXL allows repeated imaging of response properties from individual, identified neurons in vivo, which will be crucial for gaining new insights into cellular mechanisms of plasticity, regeneration and disease.}, Address = {Max Planck Institute of Neurobiology, Am Klopferspitz 18, D-82152 Martinsried, Germany.}, Author = {Mank, M and Santos, AF and Direnberger, S and Mrsic-Flogel, TD and Hofer, SB and Stein, V and Hendel, T and Reiff, DF and Levelt, C and Borst, A and Bonhoeffer, T and Hubener, M and Griesbeck, O}, Crdt = {2008/08/12 09:00}, Da = {20090123}, Date = {2008 Sep}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dep = {20080810}, Edat = {2008/08/12 09:00}, Issn = {1548-7105 (Electronic)}, Jid = {101215604}, Journal = {Nat Methods}, Jt = {Nature methods}, Keywords = {23 Technique; 21 Calcium imaging; 21 Neurophysiology;optical physiology;optical imaging;calcium imaging;frontiers review}, Language = {ENG}, Mhda = {2008/08/12 09:00}, Month = {Sep}, Number = {9}, Own = {NLM}, Pages = {805--811}, Phst = {2008/05/22 {$[$}received{$]$}; 2008/07/14 {$[$}accepted{$]$}; 2008/08/10 {$[$}aheadofprint{$]$}}, Pii = {nmeth.1243}, pmid = {18690223}, Pst = {ppublish}, Pt = {JOURNAL ARTICLE}, Status = {Publisher}, Title = {A genetically encoded calcium indicator for chronic in vivo two-photon imaging}, Volume = {5}, Year = {2008}, url = {papers/Mank_NatMethods2008.pdf}, Bdsk-File-2 = {papers/Mank_NatMethods2008a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1243}} @article{Mank:2008a, Address = {Max-Planck-Institut fur Neurobiologie, Am Klopferspitz 18, 82152 Martinsried, Germany.}, Author = {Mank, Marco and Griesbeck, Oliver}, Crdt = {2008/05/02 09:00}, Da = {20080514}, Date = {2008 May}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080804}, Dep = {20080501}, Edat = {2008/05/02 09:00}, Issn = {1520-6890 (Electronic)}, Jid = {2985134R}, Journal = {Chem Rev}, Jt = {Chemical reviews}, Keywords = {23 Technique; 21 Calcium imaging; 21 Neurophysiology;optical physiology;optical imaging;calcium imaging;frontiers review}, Language = {eng}, Mh = {Animals; Calcium/*metabolism; Calcium-Binding Proteins/metabolism; Humans; Indicators and Reagents; Kinetics; *Models, Genetic; Neurons/metabolism}, Mhda = {2008/08/05 09:00}, Month = {May}, Number = {5}, Own = {NLM}, Pages = {1550--1564}, Phst = {2008/05/01 {$[$}aheadofprint{$]$}}, Pl = {United States}, pmid = {18447377}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Review}, Rf = {105}, Rn = {0 (Calcium-Binding Proteins); 0 (Indicators and Reagents); 7440-70-2 (Calcium)}, Sb = {IM}, Status = {MEDLINE}, Title = {Genetically encoded calcium indicators}, Volume = {108}, Year = {2008}, url = {papers/Mank_ChemRev2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1021/cr078213v}} @article{Winship:2007, Abstract = {Elevation of intracellular Ca2+ in astrocytes can influence cerebral microcirculation and modulate synaptic transmission. Recently, in vivo imaging studies identified delayed, sensory-driven Ca2+ oscillations in cortical astrocytes; however, the long latencies of these Ca2+ signals raises questions in regards to their suitability for a role in short-latency modulation of cerebral microcirculation or rapid astrocyte-to-neuron communication. Here, using in vivo two-photon Ca2+ imaging, we demonstrate that approximately 5% of sulforhodamine 101-labeled astrocytes in the hindlimb area of the mouse primary somatosensory cortex exhibit short-latency (peak amplitude approximately 0.5 s after stimulus onset), contralateral hindlimb-selective sensory-evoked Ca2+ signals that operate on a time scale similar to neuronal activity and correlate with the onset of the hemodynamic response as measured by intrinsic signal imaging. The kinetics of astrocyte Ca2+ transients were similar in rise and decay times to postsynaptic neuronal transients, but decayed more slowly than neuropil Ca2+ transients that presumably reflect presynaptic transients. These in vivo findings suggest that astrocytes can respond to sensory activity in a selective manner and process information on a subsecond time scale, enabling them to potentially form an active partnership with neurons for rapid regulation of microvascular tone and neuron-astrocyte network properties.}, Address = {Department of Psychiatry, Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.}, Author = {Winship, Ian R and Plaa, Nathan and Murphy, Timothy H}, Crdt = {2007/06/08 09:00}, Da = {20070607}, Date = {2007 Jun 6}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20070703}, Edat = {2007/06/08 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology}, Language = {eng}, Mh = {Action Potentials/physiology; Animals; Astrocytes/*physiology; Calcium Signaling/*physiology; Female; Hindlimb/blood supply; Male; Mice; Mice, Inbred C57BL; Microcirculation/physiology; Neurons/*physiology; Somatosensory Cortex/*blood supply/*physiology; Time Factors}, Mhda = {2007/07/04 09:00}, Month = {Jun}, Number = {23}, Own = {NLM}, Pages = {6268--6272}, Pii = {27/23/6268}, Pl = {United States}, pmid = {17554000}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo}, Volume = {27}, Year = {2007}, url = {papers/Winship_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4801-06.2007}} @article{Van-Hooser:2007, Abstract = {The cerebral cortex, with its conserved 6-layer structure, has inspired many unifying models of function. However, recent comparative studies of primary visual cortex have revealed considerable structural diversity, raising doubts about the possibility of an all-encompassing theory. This review examines similarities and differences in V1 across mammals. Gross laminar interconnections are relatively conserved. Major functional response classes are found universally or nearly universally. Orientation and spatial frequency tuning bandwidths are quite similar despite an enormous range of visual resolution across species, and orientation tuning is contrast-invariant. Nevertheless, there is considerable diversity in the abundance of different cell classes, laminar organization, functional architecture, and functional connectivity. Orientation-selective responses arise in different layers in different species. Some mammals have elaborate columnar architecture like orientation maps and ocular dominance bands, but others lack this organization with no apparent impact on single cell properties. Finally, local functional connectivity varies according to map structure: similar cells are connected in smooth map regions but dissimilar cells are linked in animals without maps. If there is a single structure/function relation for cortex, it must accommodate significant variations in cortical circuitry. Alternatively, natural selection may craft unique circuits that function differently in each species.}, Address = {Duke University Medical Center, Durham, North Carolina 27710, USA. vanhooser@neuro.duke.edu}, Author = {Van Hooser, Stephen D}, Crdt = {2007/10/04 09:00}, Da = {20071116}, Date = {2007 Dec}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080214}, Dep = {20071002}, Edat = {2007/10/04 09:00}, Gr = {EY018064/EY/NEI NIH HHS/United States}, Issn = {1073-8584 (Print)}, Jid = {9504819}, Journal = {Neuroscientist}, Jt = {The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry}, Keywords = {21 Neurophysiology}, Language = {eng}, Mh = {Animals; *Computer Simulation; *Evolution; Humans; *Models, Neurological; Visual Cortex/*anatomy \& histology/*physiology; Visual Perception/physiology}, Mhda = {2008/02/15 09:00}, Month = {Dec}, Number = {6}, Own = {NLM}, Pages = {639--656}, Phst = {2007/10/02 {$[$}aheadofprint{$]$}}, Pii = {1073858407306597}, Pl = {United States}, pmid = {17911223}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Review}, Rf = {157}, Sb = {IM}, Status = {MEDLINE}, Title = {Similarity and diversity in visual cortex: is there a unifying theory of cortical computation?}, Volume = {13}, Year = {2007}, url = {papers/VanHooser_Neuroscientist2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1177/1073858407306597}} @article{Compte:2008, Abstract = {High-frequency oscillations in cortical networks have been linked to a variety of cognitive and perceptual processes. They have also been recorded in small cortical slices in vitro, indicating that neuronal synchronization at these frequencies is generated in the local cortical circuit. However, in vitro experiments have hitherto necessitated exogenous pharmacological or electrical stimulation to generate robust synchronized activity in the beta/gamma range. Here, we demonstrate that the isolated cortical microcircuitry generates beta and gamma oscillations spontaneously in the absence of externally applied neuromodulators or synaptic agonists. We show this in a spontaneously active slice preparation that engages in slow oscillatory activity similar to activity during slow-wave sleep. beta and gamma synchronization appeared during the up states of the slow oscillation. Simultaneous intracellular and extracellular recordings revealed synchronization between the timing of incoming synaptic events and population activity. This rhythm was mechanistically similar to pharmacologically induced gamma rhythms, as it also included sparse, irregular firing of neurons within the population oscillation, predominant involvement of inhibitory neurons, and a decrease of oscillation frequency after barbiturate application. Finally, we show in a computer model how a synaptic loop between excitatory and inhibitory neurons can explain the emergence of both the slow (<1 Hz) and the beta-range oscillations in the neocortical network. We therefore conclude that oscillations in the beta/gamma range that share mechanisms with activity reported in vivo or in pharmacologically activated in vitro preparations can be generated during slow oscillatory activity in the local cortical circuit, even without exogenous pharmacological or electrical stimulation.}, Address = {Institut d'Investigacions Biomediques August Pi i Sunyer, 08036 Barcelona, Spain. acompte@clinic.ub.es}, Author = {Compte, Albert and Reig, Ramon and Descalzo, Vanessa F and Harvey, Michael A and Puccini, Gabriel D and Sanchez-Vives, Maria V}, Crdt = {2008/12/19 09:00}, Da = {20081218}, Date = {2008 Dec 17}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090112}, Edat = {2008/12/19 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Mh = {Action Potentials/physiology; Animals; Biological Clocks/*physiology; Cerebral Cortex/*physiology; Computer Simulation; Female; Ferrets; Male; Nerve Net/*physiology; Neural Inhibition/physiology; Neural Networks (Computer); Neurons/*physiology; Organ Culture Techniques; Periodicity; Pyramidal Cells/physiology; Time Factors}, Mhda = {2009/01/13 09:00}, Month = {Dec}, Number = {51}, Own = {NLM}, Pages = {13828--13844}, Pii = {28/51/13828}, Pl = {United States}, pmid = {19091973}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Spontaneous high-frequency (10-80 Hz) oscillations during up states in the cerebral cortex in vitro}, Volume = {28}, Year = {2008}, url = {papers/Compte_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2684-08.2008}} @article{Lampl:2001, Abstract = {From the intracellularly recorded responses to small, rapidly flashed spots, we have quantitatively mapped the receptive fields of simple cells in the cat visual cortex. We then applied these maps to a feedforward model of orientation selectivity. Both the preferred orientation and the width of orientation tuning of the responses to oriented stimuli were well predicted by the model. Where tested, the tuning curve was well predicted at different spatial frequencies. The model was also successful in predicting certain features of the spatial frequency selectivity of the cells. It did not successfully predict the amplitude of the responses to drifting gratings. Our results show that the spatial organization of the receptive field can account for a large fraction of the orientation selectivity of simple cells.}, Address = {Department of Neurobiology and Physiology, Northwestern University, 2153 North Campus Drive, Evanston, IL 60208, USA. i.lamp@northwestern.edu}, Author = {Lampl, I and Anderson, J S and Gillespie, D C and Ferster, D}, Crdt = {2001/05/10 10:00}, Da = {20010509}, Date = {2001 Apr}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2009-03-26 12:10:11 -0400}, Dcom = {20010531}, Edat = {2001/05/10 10:00}, Gr = {R01 EY04726/EY/NEI NIH HHS/United States; T32 EY07128/EY/NEI NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20071114}, Mh = {Action Potentials/physiology; Animals; Cats; Neurons/cytology/*physiology; Orientation/*physiology; Pattern Recognition, Visual/*physiology; Photic Stimulation; Predictive Value of Tests; Space Perception/*physiology; Visual Cortex/cytology/*physiology}, Mhda = {2001/06/02 10:01}, Month = {Apr}, Number = {1}, Own = {NLM}, Pages = {263--274}, Pii = {S0896-6273(01)00278-1}, Pl = {United States}, pmid = {11343660}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Prediction of orientation selectivity from receptive field architecture in simple cells of cat visual cortex}, Volume = {30}, Year = {2001}, url = {papers/Lampl_Neuron2001.pdf}} @article{Tanaka:2009, Abstract = {Migrating neurons are thought to travel from their origin near the ventricle to distant territories along stereotypical pathways by detecting environmental cues in the extracellular milieu. Here, we report a novel mode of neuronal migration that challenges this view. We performed long-term, time-lapse imaging of medial ganglionic eminence (MGE)-derived cortical interneurons tangentially migrating in the marginal zone (MZ) in flat-mount cortices. We find that they exhibit a diverse range of behaviors in terms of the rate and direction of migration. Curiously, a predominant population of these neurons repeatedly changes its direction of migration in an unpredictable manner. Trajectories of migration vary from one neuron to another. The migration of individual cells lasts for long periods, sometimes up to 2 d. Theoretical analyses reveal that these behaviors can be modeled by a random walk. Furthermore, MZ cells migrate from the cortical subventricular zone to the cortical plate, transiently accumulating in the MZ. These results suggest that MGE-derived cortical interneurons, once arriving at the MZ, are released from regulation by guidance cues and initiate random walk movement, which potentially contributes to their dispersion throughout the cortex.}, Address = {Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.}, Author = {Tanaka, Daisuke H and Yanagida, Mitsutoshi and Zhu, Yan and Mikami, Sakae and Nagasawa, Takashi and Miyazaki, Jun-ichi and Yanagawa, Yuchio and Obata, Kunihiko and Murakami, Fujio}, Crdt = {2009/02/06 09:00}, Da = {20090205}, Date = {2009 Feb 4}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090224}, Edat = {2009/02/06 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {10 Development; 12 Interneuron development}, Language = {eng}, Mh = {Animals; Animals, Newborn; Cell Movement/genetics/*physiology; Cerebral Cortex/*cytology/metabolism/*physiology; Chemokine CXCL12/genetics; Gene Knock-In Techniques; Glutamate Decarboxylase/genetics; Green Fluorescent Proteins/genetics; Interneurons/*cytology/metabolism/*physiology; Mice; Mice, Inbred C57BL; Mice, Inbred ICR; Mice, Transgenic; Random Allocation; Time Factors}, Mhda = {2009/02/25 09:00}, Month = {Feb}, Number = {5}, Own = {NLM}, Pages = {1300--1311}, Pii = {29/5/1300}, Pl = {United States}, pmid = {19193877}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Chemokine CXCL12); 0 (Cxcl12 protein, mouse); 147336-22-9 (Green Fluorescent Proteins); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 1)}, Sb = {IM}, Status = {MEDLINE}, Title = {Random walk behavior of migrating cortical interneurons in the marginal zone: time-lapse analysis in flat-mount cortex}, Volume = {29}, Year = {2009}, url = {papers/Tanaka_JNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5446-08.2009}} @article{Jacobs:2007a, Abstract = {Changes in the genes encoding sensory receptor proteins are an essential step in the evolution of new sensory capacities. In primates, trichromatic color vision evolved after changes in X chromosome-linked photopigment genes. To model this process, we studied knock-in mice that expressed a human long-wavelength-sensitive (L) cone photopigment in the form of an X-linked polymorphism. Behavioral tests demonstrated that heterozygous females, whose retinas contained both native mouse pigments and human L pigment, showed enhanced long-wavelength sensitivity and acquired a new capacity for chromatic discrimination. An inherent plasticity in the mammalian visual system thus permits the emergence of a new dimension of sensory experience based solely on gene-driven changes in receptor organization.}, Address = {Neuroscience Research Institute and Department of Psychology, University of California, Santa Barbara, CA 93106, USA. jacobs@psych.ucsb.edu}, Author = {Jacobs, Gerald H and Williams, Gary A and Cahill, Hugh and Nathans, Jeremy}, Cin = {Science. 2007 Oct 12;318(5848):196; author reply 196. PMID: 17932271}, Crdt = {2007/03/24 09:00}, Da = {20070323}, Date = {2007 Mar 23}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20070405}, Edat = {2007/03/24 09:00}, Gr = {EY002052/EY/NEI NIH HHS/United States}, Issn = {1095-9203 (Electronic)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Neurophysiology}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Color Perception/*genetics; Discrimination (Psychology); Electroretinography; *Evolution; Female; Genetic Engineering; Heterozygote; Humans; Light; Male; Mice; Neuronal Plasticity; Primates/genetics/physiology; Retinal Cone Photoreceptor Cells/*physiology; Retinal Pigments/*genetics/*physiology; X Chromosome/genetics; X Chromosome Inactivation}, Mhda = {2007/04/06 09:00}, Month = {Mar}, Number = {5819}, Own = {NLM}, Pages = {1723--1725}, Pii = {315/5819/1723}, Pl = {United States}, pmid = {17379811}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Retinal Pigments)}, Sb = {IM}, Status = {MEDLINE}, Title = {Emergence of novel color vision in mice engineered to express a human cone photopigment}, Volume = {315}, Year = {2007}, url = {papers/Jacobs_Science2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1138838}} @article{Soucy:2009, Abstract = {We explored the map of odor space created by glomeruli on the olfactory bulb of both rat and mouse. Identified glomeruli could be matched across animals by their response profile to hundreds of odors. Their layout in different individuals varied by only approximately 1 glomerular spacing, corresponding to a precision of 1 part in 1,000. Across species, mouse and rat share many glomeruli with apparently identical odor tuning, arranged in a similar layout. In mapping the position of a glomerulus to its odor tuning, we found only a coarse relationship with a precision of approximately 5 spacings. No chemotopic order was apparent on a finer scale and nearby glomeruli were almost as diverse in their odor sensitivity as distant ones. This local diversity of sensory tuning stands in marked distinction from other brain maps. Given the reliable placement of the glomeruli, it represents a feature, not a flaw, of the olfactory bulb.}, Address = {Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, 52 Oxford Street, Cambridge, Massachusetts 02138, USA.}, Author = {Soucy, Edward R and Albeanu, Dinu F and Fantana, Antoniu L and Murthy, Venkatesh N and Meister, Markus}, Cin = {Nat Neurosci. 2009 Feb;12(2):103-4. PMID: 19172161}, Crdt = {2009/01/20 09:00}, Da = {20090127}, Date = {2009 Feb}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090227}, Dep = {20090118}, Edat = {2009/01/20 09:00}, Issn = {1546-1726 (Electronic)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {13 Olfactory bulb anatomy}, Language = {eng}, Mh = {Animals; *Brain Mapping; Female; Green Fluorescent Proteins/genetics; Male; Mice; Mice, Mutant Strains; Models, Neurological; Odors; Olfactory Bulb/*cytology/*physiology; Olfactory Pathways/*cytology/*physiology; Olfactory Receptor Neurons/cytology/physiology; Rats; Rats, Long-Evans; Rats, Wistar; Receptors, Odorant/genetics/metabolism; Smell/*physiology}, Mhda = {2009/02/28 09:00}, Month = {Feb}, Number = {2}, Own = {NLM}, Pages = {210--220}, Phst = {2008/09/24 {$[$}received{$]$}; 2008/12/18 {$[$}accepted{$]$}; 2009/01/18 {$[$}aheadofprint{$]$}}, Pii = {nn.2262}, Pl = {United States}, pmid = {19151709}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {0 (Receptors, Odorant); 147336-22-9 (Green Fluorescent Proteins)}, Sb = {IM}, Status = {MEDLINE}, Title = {Precision and diversity in an odor map on the olfactory bulb}, Volume = {12}, Year = {2009}, url = {papers/Soucy_NatNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2262}} @article{Goldin:2007, Abstract = {GABAergic interneurons of the hippocampus play an important role in the generation of behaviorally relevant network oscillations. Among this heterogeneous neuronal population, somatostatin (SOM)-positive oriens-lacunosum moleculare (O-LM) interneurons are remarkable because they are tuned to operate at theta frequencies (6-10 Hz) in vitro and in vivo. Recent studies show that a high proportion of glutamatergic synapses that impinge on O-LM interneurons are mediated by kainate receptors (KA-Rs). In the present study, we thus tested the hypothesis that KA-Rs transmit afferent inputs in O-LM neurons during synaptic stimulation at theta frequency. We combined multibeam two-photon calcium imaging in hippocampal slices from SOM-enhanced green fluorescent protein (EGFP) mice, to record the activity of SOM cells as well as hundreds of neurons simultaneously, and targeted electrophysiological recordings and morphological analysis to describe the morphofunctional features of particular cells. We report that EGFP-positive O-LM neurons are the only subtype of interneuron that reliably follows synaptic stimulation of the alveus in the theta frequency range. Electrophysiological recordings revealed the crucial contribution of KA-Rs to the firing activity and to the glutamatergic response to theta stimuli in O-LM cells compared with other cell types. The reliable activation of O-LM cells in the theta frequency range did not simply result from the longer kinetics of KA-R-mediated postsynaptic events (EPSP(KA)) but presumably from a specific interaction between EPSP(KA) and their intrinsic active membrane properties. Such preferential processing of excitatory inputs via KA-Rs by distally projecting GABAergic microcircuits could provide a key role in theta band frequency oscillations.}, Address = {Institut de Neurobiologie de la Mediteranee, Inserm, Unite 29, Universite de la Mediterranee, Parc Scientifique de Luminy, 13273 Marseille cedex 9, France.}, Author = {Goldin, Miri and Epsztein, Jerome and Jorquera, Isabel and Represa, Alfonso and Ben-Ari, Yehezkel and Crepel, Valerie and Cossart, Rosa}, Crdt = {2007/09/07 09:00}, Da = {20070906}, Date = {2007 Sep 5}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20071002}, Edat = {2007/09/07 09:00}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Neurophysiology; 21 Cortical oscillations}, Language = {eng}, Mh = {Action Potentials/physiology; Animals; Calcium Signaling/physiology; Electric Stimulation; Electrophysiology; Excitatory Postsynaptic Potentials/physiology; Glutamic Acid/metabolism; Green Fluorescent Proteins/biosynthesis/genetics; Hippocampus/cytology/*physiology; Interneurons/*physiology; Mice; Mice, Transgenic; Patch-Clamp Techniques; Pyramidal Cells/physiology; Receptors, Kainic Acid/*physiology; Synapses/*physiology; *Theta Rhythm}, Mhda = {2007/10/03 09:00}, Month = {Sep}, Number = {36}, Own = {NLM}, Pages = {9560--9572}, Pii = {27/36/9560}, Pl = {United States}, pmid = {17804617}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Receptors, Kainic Acid); 0 (enhanced green fluorescent protein); 147336-22-9 (Green Fluorescent Proteins); 56-86-0 (Glutamic Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Synaptic kainate receptors tune oriens-lacunosum moleculare interneurons to operate at theta frequency}, Volume = {27}, Year = {2007}, url = {papers/Goldin_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1237-07.2007}} @article{McKinney:2009, Abstract = {Photoconvertible fluorescent proteins are potential tools for investigating dynamic processes in living cells and for emerging super-resolution microscopy techniques. Unfortunately, most probes in this class are hampered by oligomerization, small photon budgets or poor photostability. Here we report an EosFP variant that functions well in a broad range of protein fusions for dynamic investigations, exhibits high photostability and preserves the approximately 10-nm localization precision of its parent.}, Address = {Howard Hughes Medical Institute, Janelia Farm Research Campus, 19700 Helix Drive, Ashburn, Virginia 20147, USA.}, Author = {McKinney, Sean A and Murphy, Christopher S and Hazelwood, Kristin L and Davidson, Michael W and Looger, Loren L}, Cin = {Nat Methods. 2009 Feb;6(2):124-5. PMID: 19180093}, Crdt = {2009/01/27 09:00}, Da = {20090130}, Date = {2009 Feb}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090223}, Dep = {20090125}, Edat = {2009/01/27 09:00}, Gr = {Howard Hughes Medical Institute/United States}, Issn = {1548-7105 (Electronic)}, Jid = {101215604}, Journal = {Nat Methods}, Jt = {Nature methods}, Keywords = {23 Technique}, Language = {eng}, Mh = {Animals; Fibroblasts; Fluorescent Dyes/*chemistry; Hela Cells; Humans; Luminescent Proteins/*chemistry/genetics; Microscopy, Fluorescence/methods; Mutagenesis, Site-Directed; Photochemical Processes; Recombinant Fusion Proteins/chemistry}, Mhda = {2009/02/24 09:00}, Month = {Feb}, Number = {2}, Own = {NLM}, Pages = {131--133}, Phst = {2008/10/31 {$[$}received{$]$}; 2008/12/15 {$[$}accepted{$]$}; 2009/01/25 {$[$}aheadofprint{$]$}}, Pii = {nmeth.1296}, Pl = {United States}, pmid = {19169260}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Fluorescent Dyes); 0 (Luminescent Proteins); 0 (Recombinant Fusion Proteins)}, Sb = {IM}, Status = {MEDLINE}, Title = {A bright and photostable photoconvertible fluorescent protein}, Volume = {6}, Year = {2009}, url = {papers/McKinney_NatMethods2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1296}} @article{Manent:2009, Abstract = {Disorders of neuronal migration can lead to malformations of the cerebral neocortex that greatly increase the risk of seizures. It remains untested whether malformations caused by disorders in neuronal migration can be reduced by reactivating cellular migration and whether such repair can decrease seizure risk. Here we show, in a rat model of subcortical band heterotopia (SBH) generated by in utero RNA interference of the Dcx gene, that aberrantly positioned neurons can be stimulated to migrate by reexpressing Dcx after birth. Restarting migration in this way both reduces neocortical malformations and restores neuronal patterning. We further find that the capacity to reduce SBH continues into early postnatal development. Moreover, intervention after birth reduces the convulsant-induced seizure threshold to a level similar to that in malformation-free controls. These results suggest that disorders of neuronal migration may be eventually treatable by reengaging developmental programs both to reduce the size of cortical malformations and to reduce seizure risk.}, Address = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA.}, Author = {Manent, Jean-Bernard and Wang, Yu and Chang, Yoonjeung and Paramasivam, Murugan and LoTurco, Joseph J}, Cin = {Nat Med. 2009 Jan;15(1):17-8. PMID: 19129774}, Crdt = {2008/12/23 09:00}, Da = {20090108}, Date = {2009 Jan}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090204}, Dep = {20081221}, Edat = {2008/12/23 09:00}, Gr = {MH056524/MH/NIMH NIH HHS/United States; NS062416/NS/NINDS NIH HHS/United States}, Issn = {1546-170X (Electronic)}, Jid = {9502015}, Journal = {Nat Med}, Jt = {Nature medicine}, Keywords = {21 Dysplasia-heterotopia; 10 Development; 10 genetics malformation}, Language = {eng}, Mh = {Animals; Animals, Genetically Modified; Cell Movement/genetics; Classical Lissencephalies and Subcortical Band Heterotopias/*genetics/pathology/therapy/veterinary; *Disease Models, Animal; Female; Gene Knockdown Techniques; Gene Therapy; Genetic Predisposition to Disease; Microtubule-Associated Proteins/antagonists \& inhibitors/*genetics/physiology; Models, Biological; Neuronal Migration Disorders/embryology/genetics/pathology/veterinary; Neurons/pathology/physiology; Neuropeptides/antagonists \& inhibitors/*genetics/physiology; Pregnancy; RNA Interference/physiology; Rats; Seizures/*genetics/pathology/therapy; Severity of Illness Index}, Mhda = {2009/02/05 09:00}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {84--90}, Phst = {2008/05/15 {$[$}received{$]$}; 2008/11/06 {$[$}accepted{$]$}; 2008/12/21 {$[$}aheadofprint{$]$}}, Pii = {nm.1897}, Pl = {United States}, pmid = {19098909}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Microtubule-Associated Proteins); 0 (Neuropeptides); 0 (doublecortin protein)}, Sb = {IM}, Status = {MEDLINE}, Title = {Dcx reexpression reduces subcortical band heterotopia and seizure threshold in an animal model of neuronal migration disorder}, Volume = {15}, Year = {2009}, url = {papers/Manent_NatMed2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm.1897}} @article{Katzner:2009, Abstract = {The local field potential (LFP) is increasingly used to measure the combined activity of neurons within a region of tissue. Yet, available estimates of the size of this region are highly disparate, ranging from several hundred microns to a few millimeters. To measure the size of this region directly, we used a combination of multielectrode recordings and optical imaging. We determined the orientation selectivity of stimulus-evoked LFP signals in primary visual cortex and were able to predict it on the basis of the surrounding map of orientation preference. The results show that > 95% of the LFP signal originates within 250 microm of the recording electrode. This quantitative estimate indicates that LFPs are more local than often recognized and provides a guide to the interpretation of the increasing number of studies that rest on LFP recordings.}, Address = {Smith-Kettlewell Eye Research Institute, San Francisco, CA 94115, USA.}, Author = {Katzner, Steffen and Nauhaus, Ian and Benucci, Andrea and Bonin, Vincent and Ringach, Dario L and Carandini, Matteo}, Cin = {Neuron. 2009 Jan 15;61(1):1-2. PMID: 19146806}, Crdt = {2009/01/17 09:00}, Da = {20090116}, Date = {2009 Jan 15}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090205}, Edat = {2009/01/17 09:00}, Gr = {EY12816/EY/NEI NIH HHS/United States; EY17396/EY/NEI NIH HHS/United States; EY18322/EY/NEI NIH HHS/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Mh = {Animals; Cats; Electrodes; Electrophysiology/methods; Evoked Potentials, Visual/*physiology; Neurons/*physiology; Visual Cortex/cytology/*physiology; Visual Perception/physiology}, Mhda = {2009/02/06 09:00}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {35--41}, Phst = {2008/04/02 {$[$}received{$]$}; 2008/09/15 {$[$}revised{$]$}; 2008/11/07 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)01006-4}, Pl = {United States}, pmid = {19146811}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Local origin of field potentials in visual cortex}, Volume = {61}, Year = {2009}, url = {papers/Katzner_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.11.016}} @article{White:2007, Abstract = {Functional maps arise in developing visual cortex as response selectivities become organized into columnar patterns of population activity. Recent studies of developing orientation and direction maps indicate that both are sensitive to visual experience, but not to the same degree or duration. Direction maps have a greater dependence on early vision, while orientation maps remain sensitive to experience for a longer period of cortical maturation. There is also a darker side to experience: abnormal vision through closed lids produces severe impairments in neuronal selectivity, rendering these maps nearly undetectable. Thus, the rules that govern their formation and the construction of the underlying neural circuits are modulated-for better or worse-by early vision. Direction maps, and possibly maps of other properties that are dependent upon precise conjunctions of spatial and temporal signals, are most susceptible to the potential benefits and maladaptive consequences of early sensory experience.}, Address = {Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. len.white@duke.edu}, Author = {White, Leonard E and Fitzpatrick, David}, Crdt = {2007/10/30 09:00}, Da = {20071029}, Date = {2007 Oct 25}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20071219}, Edat = {2007/10/30 09:00}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Humans; Vision, Ocular/*physiology; Visual Cortex/growth \& development/*physiology; Visual Pathways/growth \& development/*physiology; Visual Perception/physiology}, Mhda = {2007/12/20 09:00}, Month = {Oct}, Number = {2}, Own = {NLM}, Pages = {327--338}, Pii = {S0896-6273(07)00773-8}, Pl = {United States}, pmid = {17964249}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review}, Rating = {5}, Rf = {120}, Sb = {IM}, Status = {MEDLINE}, Title = {Vision and cortical map development}, Volume = {56}, Year = {2007}, url = {papers/White_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.10.011}} @article{Lagace:2007, Abstract = {Understanding the fate of adult-generated neurons and the mechanisms that influence them requires consistent labeling and tracking of large numbers of stem cells. We generated a nestin-CreER(T2)/R26R-yellow fluorescent protein (YFP) mouse to inducibly label nestin-expressing stem cells and their progeny in the adult subventricular zone (SVZ) and subgranular zone (SGZ). Several findings show that the estrogen ligand tamoxifen (TAM) specifically induced recombination in stem cells and their progeny in nestin-CreER(T2)/R26R-YFP mice: 97% of SGZ stem-like cells (GFAP/Sox2 with radial glial morphology) expressed YFP; YFP+ neurospheres could be generated in vitro after recombination in vivo, and maturing YFP+ progeny were increasingly evident in the olfactory bulb (OB) and dentate gyrus (DG) granule cell layer. Revealing an unexpected regional dissimilarity in adult neurogenesis, YFP+ cells accumulated up to 100 d after TAM in the OB, but in the SGZ, YFP+ cells reached a plateau 30 d after TAM. In addition, most SVZ and SGZ YFP+ cells became neurons, underscoring a link between nestin and neuronal fate. Finally, quantification of YFP+ cells in nestin-CreER(T2)/R26R-YFP mice allowed us to estimate, for example, that stem cells and their progeny contribute to no more than 1% of the adult DG granule cell layer. In addition to revealing the dynamic contribution of nestin-expressing stem cells to adult neurogenesis, this work highlights the utility of the nestin-CreER(T2)/R26R-YFP mouse for inducible gene ablation in stem cells and their progeny in vivo in the two major regions of adult neurogenesis.}, Address = {Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9070, USA.}, Author = {Lagace, Diane C and Whitman, Mary C and Noonan, Michele A and Ables, Jessica L and DeCarolis, Nathan A and Arguello, Amy A and Donovan, Michael H and Fischer, Stephanie J and Farnbauch, Laure A and Beech, Robert D and DiLeone, Ralph J and Greer, Charles A and Mandyam, Chitra D and Eisch, Amelia J}, Crdt = {2007/11/16 09:00}, Da = {20071116}, Date = {2007 Nov 14}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20071219}, Edat = {2007/11/16 09:00}, Gr = {DA016765/DA/NIDA NIH HHS/United States; DA018017/DA/NIDA NIH HHS/United States; DA07290/DA/NIDA NIH HHS/United States; DA16765-02S1/DA/NIDA NIH HHS/United States; DC00213/DC/NIDCD NIH HHS/United States; DC006972/DC/NIDCD NIH HHS/United States; GM07205/GM/NIGMS NIH HHS/United States; MH754572/MH/NIMH NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {02 Adult neurogenesis migration}, Language = {eng}, Mh = {Animals; Brain/cytology/*metabolism; Cell Differentiation/drug effects/*physiology; Cell Lineage/drug effects/*physiology; Cell Proliferation/drug effects; Dentate Gyrus/cytology/metabolism; Gene Targeting/methods; Intermediate Filament Proteins/*metabolism; Luminescent Proteins/genetics/metabolism; Mice; Mice, Transgenic; Models, Animal; Nerve Regeneration/drug effects/physiology; Nerve Tissue Proteins/*metabolism; Neuroglia/cytology/drug effects/metabolism; Neurons/*metabolism; Olfactory Bulb/cytology/metabolism; Recombinant Fusion Proteins/genetics/metabolism; Recombination, Genetic/drug effects/genetics; Selective Estrogen Receptor Modulators/pharmacology; Stem Cells/drug effects/*metabolism; Tamoxifen/pharmacology}, Mhda = {2007/12/20 09:00}, Month = {Nov}, Number = {46}, Own = {NLM}, Pages = {12623--12629}, Pii = {27/46/12623}, Pl = {United States}, pmid = {18003841}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Intermediate Filament Proteins); 0 (Luminescent Proteins); 0 (Nerve Tissue Proteins); 0 (Recombinant Fusion Proteins); 0 (Selective Estrogen Receptor Modulators); 0 (nestin); 0 (yellow fluorescent protein, mouse); 10540-29-1 (Tamoxifen)}, Sb = {IM}, Status = {MEDLINE}, Title = {Dynamic contribution of nestin-expressing stem cells to adult neurogenesis}, Volume = {27}, Year = {2007}, url = {papers/Lagace_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3812-07.2007}} @article{Lefort:2009, Abstract = {Local microcircuits within neocortical columns form key determinants of sensory processing. Here, we investigate the excitatory synaptic neuronal network of an anatomically defined cortical column, the C2 barrel column of mouse primary somatosensory cortex. This cortical column is known to process tactile information related to the C2 whisker. Through multiple simultaneous whole-cell recordings, we quantify connectivity maps between individual excitatory neurons located across all cortical layers of the C2 barrel column. Synaptic connectivity depended strongly upon somatic laminar location of both presynaptic and postsynaptic neurons, providing definitive evidence for layer-specific signaling pathways. The strongest excitatory influence upon the cortical column was provided by presynaptic layer 4 neurons. In all layers we found rare large-amplitude synaptic connections, which are likely to contribute strongly to reliable information processing. Our data set provides the first functional description of the excitatory synaptic wiring diagram of a physiologically relevant and anatomically well-defined cortical column at single-cell resolution.}, Address = {Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique Federale de Lausanne, CH1015, Switzerland.}, Author = {Lefort, Sandrine and Tomm, Christian and Floyd Sarria, J-C and Petersen, Carl C H}, Crdt = {2009/02/03 09:00}, Da = {20090202}, Date = {2009 Jan 29}, Date-Added = {2009-03-26 11:57:41 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090305}, Edat = {2009/02/03 09:00}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Neurophysiology}, Language = {eng}, Mh = {Action Potentials/physiology; Afferent Pathways/cytology/physiology; Animals; Excitatory Postsynaptic Potentials/physiology; Fluorescent Dyes; Mechanoreceptors/cytology/physiology; Mice; Mice, Inbred C57BL; Nerve Net/cytology/*physiology; Neural Pathways/cytology/physiology; Neurons/cytology/*physiology; Organ Culture Techniques; Patch-Clamp Techniques; Somatosensory Cortex/cytology/*physiology; Staining and Labeling; Synapses/physiology/ultrastructure; Synaptic Transmission/*physiology; Touch/physiology; Trigeminal Nerve/cytology/physiology; Vibrissae/cytology/physiology}, Mhda = {2009/03/06 09:00}, Month = {Jan}, Number = {2}, Own = {NLM}, Pages = {301--316}, Phst = {2008/08/04 {$[$}received{$]$}; 2008/12/04 {$[$}revised{$]$}; 2008/12/04 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)01092-1}, Pl = {United States}, pmid = {19186171}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Fluorescent Dyes)}, Sb = {IM}, Status = {MEDLINE}, Title = {The excitatory neuronal network of the C2 barrel column in mouse primary somatosensory cortex}, Volume = {61}, Year = {2009}, url = {papers/Lefort_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.12.020}} @article{Champoux:2008, Abstract = {The present study aimed at investigating the effects of early visual deprivation (bilateral neonatal enucleation) on auditory and somatosensory coding in the polysensory deep layers of the superior colliculus of the rat. The proportion of cells responding to auditory and somatosensory stimulation and the receptive field properties of single neurons were assessed in both normal and enucleated rats. As expected, in enucleated rats there was a drastic increase in the number of unresponsive units and visual responses could no longer be evoked. Most importantly, the proportion of cells that responded to auditory stimulation was drastically reduced. However, the few cells that remained responsive to auditory stimulation were well tuned to noise stimuli presented in both azimuth and elevation, principally in the contralateral hemifield. Enucleation also increased the proportion of cells responding to somatosensory stimulation, particularly to the vibrissae. Implications in terms of neural plasticity and functionality are discussed.}, Address = {Centre de Recherche en Neuropsychologie et Cognition, Universite de Montreal, Montreal, Quebec, Canada.}, Author = {Champoux, Francois and Bacon, Benoit A and Lepore, Franco and Guillemot, Jean-Paul}, Crdt = {2007/12/25 09:00}, Da = {20080121}, Date = {2008 Jan 29}, Date-Added = {2009-03-26 11:41:24 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20080519}, Dep = {20071112}, Edat = {2007/12/25 09:00}, Issn = {0006-8993 (Print)}, Jid = {0045503}, Journal = {Brain Res}, Jt = {Brain research}, Keywords = {21 Activity-development}, Language = {eng}, Mh = {Acoustic Stimulation; Adaptation, Physiological/physiology; Animals; Evoked Potentials, Somatosensory/physiology; Eye Enucleation; Neuronal Plasticity/physiology; Neurons/physiology; Photic Stimulation; Rats; Rats, Long-Evans; Sensory Deprivation/*physiology; Sound Localization/*physiology; Space Perception/*physiology; Superior Colliculi/anatomy \& histology/*physiology; Touch/*physiology; Vibrissae/physiology; Vision, Binocular/*physiology}, Mhda = {2008/05/20 09:00}, Month = {Jan}, Own = {NLM}, Pages = {84--95}, Phst = {2007/06/27 {$[$}received{$]$}; 2007/11/02 {$[$}revised{$]$}; 2007/11/05 {$[$}accepted{$]$}; 2007/11/12 {$[$}aheadofprint{$]$}}, Pii = {S0006-8993(07)02656-X}, Pl = {Netherlands}, pmid = {18155185}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Effects of early binocular enucleation on auditory and somatosensory coding in the superior colliculus of the rat}, Volume = {1191}, Year = {2008}, url = {papers/Champoux_BrainRes2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainres.2007.11.003}} @article{Sirota:2008, Abstract = {Although it has been tacitly assumed that the hippocampus exerts an influence on neocortical networks, the mechanisms of this process are not well understood. We examined whether and how hippocampal theta oscillations affect neocortical assembly patterns by recording populations of single cells and transient gamma oscillations in multiple cortical regions, including the somatosensory area and prefrontal cortex in behaving rats and mice. Laminar analysis of neocortical gamma bursts revealed multiple gamma oscillators of varying frequency and location, which were spatially confined and synchronized local groups of neurons. A significant fraction of putative pyramidal cells and interneurons as well as localized gamma oscillations in all recorded neocortical areas were phase biased by the hippocampal theta rhythm. We hypothesize that temporal coordination of neocortical gamma oscillators by hippocampal theta is a mechanism by which information contained in spatially widespread neocortical assemblies can be synchronously transferred to the associative networks of the hippocampus.}, Address = {Center for Molecular and Behavioral Neuroscience, Rutgers, State University of New Jersey, 197 University Avenue, Newark, NJ 07102, USA.}, Author = {Sirota, Anton and Montgomery, Sean and Fujisawa, Shigeyoshi and Isomura, Yoshikazu and Zugaro, Michael and Buzsaki, Gyorgy}, Crdt = {2008/11/29 09:00}, Da = {20081128}, Date = {2008 Nov 26}, Date-Added = {2009-03-26 11:41:24 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090116}, Edat = {2008/11/29 09:00}, Gr = {MH54671/MH/NIMH NIH HHS/United States; NS034994/NS/NINDS NIH HHS/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20090212}, Mh = {Animals; Biological Clocks/*physiology; Evoked Potentials/*physiology; Hippocampus/*physiology; Interneurons/physiology; Mice; Neocortex/*physiology; Nerve Net/physiology; Neural Inhibition/physiology; Neural Pathways/physiology; Neurons/*physiology; Pyramidal Cells/physiology; Rats; *Theta Rhythm}, Mhda = {2009/01/17 09:00}, Mid = {NIHMS83122}, Month = {Nov}, Number = {4}, Oid = {NLM: NIHMS83122 {$[$}Available on 11/26/09{$]$}; NLM: PMC2640228 {$[$}Available on 11/26/09{$]$}}, Own = {NLM}, Pages = {683--697}, Phst = {2008/02/12 {$[$}received{$]$}; 2008/06/22 {$[$}revised{$]$}; 2008/09/04 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00762-9}, Pl = {United States}, Pmc = {PMC2640228}, Pmcr = {2009/11/26}, pmid = {19038224}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Entrainment of neocortical neurons and gamma oscillations by the hippocampal theta rhythm}, Volume = {60}, Year = {2008}, url = {papers/Sirota_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.09.014}} @article{Han:2008, Abstract = {Spontaneous waves of activity propagating across large cortical areas may play important roles in sensory processing and circuit refinement. However, whether these waves are in turn shaped by sensory experience remains unclear. Here we report that visually evoked cortical activity reverberates in subsequent spontaneous waves. Voltage-sensitive dye imaging in rat visual cortex shows that following repetitive presentation of a given visual stimulus, spatiotemporal activity patterns resembling the evoked response appear more frequently in the spontaneous waves. This effect is specific to the response pattern evoked by the repeated stimulus, and it persists for several minutes without further visual stimulation. Such wave-mediated reverberation could contribute to short-term memory and help to consolidate the transient effects of recent sensory experience into long-lasting cortical modifications.}, Address = {Group in Vision Science, University of California Berkeley, Berkeley, CA 94720, USA.}, Author = {Han, Feng and Caporale, Natalia and Dan, Yang}, Crdt = {2008/10/30 09:00}, Da = {20081029}, Date = {2008 Oct 23}, Date-Added = {2009-03-26 11:41:24 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081126}, Edat = {2008/10/30 09:00}, Gr = {Howard Hughes Medical Institute/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {currOpinRvw; 21 Cortical oscillations; 21 Neurophysiology; retinal wave paper; voltage sensor; optical physiology; optical imaging; 21 Activity-development; Spontaneous activity}, Language = {eng}, Mh = {Action Potentials/physiology; Animals; Evoked Potentials/physiology; Evoked Potentials, Visual/*physiology; Fluorescent Dyes; Learning/physiology; Memory, Short-Term/*physiology; Nerve Net/physiology; Neurons/physiology; Photic Stimulation; Rats; Rats, Long-Evans; Staining and Labeling; Visual Cortex/*physiology; Visual Pathways/physiology; Visual Perception/*physiology}, Mhda = {2008/12/17 09:00}, Month = {Oct}, Number = {2}, Own = {NLM}, Pages = {321--327}, Phst = {2008/03/10 {$[$}received{$]$}; 2008/07/07 {$[$}revised{$]$}; 2008/08/26 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00767-8}, Pl = {United States}, pmid = {18957223}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Fluorescent Dyes)}, Sb = {IM}, Status = {MEDLINE}, Title = {Reverberation of recent visual experience in spontaneous cortical waves}, Volume = {60}, Year = {2008}, url = {papers/Han_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.08.026}} @article{Boldogkoi:2009, Abstract = {We developed retrograde, transsynaptic pseudorabies viruses (PRVs) with genetically encoded activity sensors that optically report the activity of connected neurons among spatially intermingled neurons in the brain. Next we engineered PRVs to express two differentially colored fluorescent proteins in a time-shifted manner to define a time period early after infection to investigate neural activity. Finally we used multiple-colored PRVs to differentiate and dissect the complex architecture of brain regions.}, Address = {Department of Medical Biology, Faculty of Medicine, University of Szeged, Somogyi B. u. 4., Szeged, H-6720, Hungary.}, Author = {Boldogkoi, Zsolt and Balint, Kamill and Awatramani, Gautam B and Balya, David and Busskamp, Volker and Viney, Tim James and Lagali, Pamela S and Duebel, Jens and Pasti, Emese and Tombacz, Dora and Toth, Judit S and Takacs, Irma F and Scherf, Brigitte Gross and Roska, Botond}, Crdt = {2009/01/06 09:00}, Da = {20090130}, Date = {2009 Feb}, Date-Added = {2009-03-26 11:41:24 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090223}, Dep = {20090104}, Edat = {2009/01/06 09:00}, Issn = {1548-7105 (Electronic)}, Jid = {101215604}, Journal = {Nat Methods}, Jt = {Nature methods}, Keywords = {23 Technique;optical imaging;optical physiology;21 Neurophysiology;calcium imaging;calcium sensor;Trans-synaptic;viral gene transfer;Gene Transfer Techniques;frontiers review;Imaging;21 Circuit structure-function;connectivity}, Language = {eng}, Mh = {Animals; Biosensing Techniques/methods; Brain/cytology/physiology; Green Fluorescent Proteins/*analysis/biosynthesis/genetics; Herpesvirus 1, Suid/genetics/*metabolism; Luminescent Proteins/*analysis/biosynthesis/genetics; Mice; Neurons/physiology/virology; Synaptic Transmission/*physiology; Time Factors; Visual Pathways/physiology/*virology}, Mhda = {2009/02/24 09:00}, Month = {Feb}, Number = {2}, Own = {NLM}, Pages = {127--130}, Phst = {2008/05/29 {$[$}received{$]$}; 2008/12/01 {$[$}accepted{$]$}; 2009/01/04 {$[$}aheadofprint{$]$}}, Pii = {nmeth.1292}, Pl = {United States}, pmid = {19122667}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.}, Rn = {0 (Luminescent Proteins); 0 (red fluorescent protein); 147336-22-9 (Green Fluorescent Proteins)}, Sb = {IM}, Status = {MEDLINE}, Title = {Genetically timed, activity-sensor and rainbow transsynaptic viral tools}, Volume = {6}, Year = {2009}, url = {papers/Boldogkoi_NatMethods2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1292}} @article{Brustein:2003, Abstract = {The zebrafish larva is a powerful model for the analysis of behaviour and the underlying neuronal network activity during early stages of development. Here we employ a new approach of "in vivo" Ca(2+) imaging in this preparation. We demonstrate that bolus injection of membrane-permeable Ca(2+) indicator dyes into the spinal cord of zebrafish larvae results in rapid staining of essentially the entire spinal cord. Using two-photon imaging, we could monitor Ca(2+) signals simultaneously from a large population of spinal neurons with single-cell resolution. To test the method, Ca(2+) transients were produced by iontophoretic application of glutamate and, as observed for the first time in a living preparation, of GABA or glycine. Glycine-evoked Ca(2+) transients were blocked by the application of strychnine. Sensory stimuli that trigger escape reflexes in mobile zebrafish evoked Ca(2+) transients in distinct neurons of the spinal network. Moreover, long-term recordings revealed spontaneous Ca(2+) transients in individual spinal neurons. Frequently, this activity occurred synchronously among many neurons in the network. In conclusion, the new approach permits a reliable analysis with single-cell resolution of the functional organisation of developing neuronal networks.}, Address = {McGill Centre for Research in Neuroscience and Department of Biology, McGill University, H3G 1A4, Montreal, Quebec, Canada.}, Author = {Brustein, E and Marandi, N and Kovalchuk, Y and Drapeau, P and Konnerth, A}, Crdt = {2003/07/29 05:00}, Da = {20030923}, Date = {2003 Sep}, Date-Added = {2009-03-26 11:41:24 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20040607}, Dep = {20030722}, Edat = {2003/07/29 05:00}, Issn = {0031-6768 (Print)}, Jid = {0154720}, Journal = {Pflugers Arch}, Jt = {Pflugers Archiv : European journal of physiology}, Keywords = {21 Calcium imaging}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Calcium/chemistry/*physiology; Calcium Signaling/drug effects/physiology; Coloring Agents; *Diagnostic Imaging; Excitatory Amino Acids/antagonists \& inhibitors/pharmacology; Fluorescent Dyes; Glycine Agents/pharmacology; Larva/physiology; Nerve Net/drug effects/growth \& development/*physiology; Neurons/physiology; Spinal Cord/cytology/growth \& development/physiology; Strychnine/pharmacology; Zebrafish/*physiology}, Mhda = {2004/06/21 10:00}, Month = {Sep}, Number = {6}, Own = {NLM}, Pages = {766--773}, Phst = {2003/05/02 {$[$}received{$]$}; 2003/06/24 {$[$}accepted{$]$}; 2003/07/22 {$[$}aheadofprint{$]$}}, Pl = {Germany}, pmid = {12883893}, Pst = {ppublish}, Pt = {In Vitro; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Coloring Agents); 0 (Excitatory Amino Acids); 0 (Fluorescent Dyes); 0 (Glycine Agents); 57-24-9 (Strychnine); 7440-70-2 (Calcium)}, Sb = {IM}, Status = {MEDLINE}, Title = {"In vivo" monitoring of neuronal network activity in zebrafish by two-photon Ca(2+) imaging}, Volume = {446}, Year = {2003}, url = {papers/Brustein_PflugersArch2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00424-003-1138-4}} @article{Roxin:2008, Abstract = {Calcium imaging of the spontaneous activity in cortical slices has revealed repeating spatiotemporal patterns of transitions between so-called down states and up states (Ikegaya et al., 2004). Here we fit a model network of stochastic binary neurons to data from these experiments, and in doing so reproduce the distributions of such patterns. We use two versions of this model: (1) an unconnected network in which neurons are activated as independent Poisson processes; and (2) a network with an interaction matrix, estimated from the data, representing effective interactions between the neurons. The unconnected model (model 1) is sufficient to account for the statistics of repeating patterns in 11 of the 15 datasets studied. Model 2, with interactions between neurons, is required to account for pattern statistics of the remaining four. Three of these four datasets are the ones that contain the largest number of transitions, suggesting that long datasets are in general necessary to render interactions statistically visible. We then study the topology of the matrix of interactions estimated for these four datasets. For three of the four datasets, we find sparse matrices with long-tailed degree distributions and an overrepresentation of certain network motifs. The remaining dataset exhibits a strongly interconnected, spatially localized subgroup of neurons. In all cases, we find that interactions between neurons facilitate the generation of long patterns that do not repeat exactly.}, Address = {Computational Neuroscience, Department of Information and Communication Technologies, Universitat Pompeu Fabra, 08003 Barcelona, Spain. alexander.roxin@upf.edu}, Author = {Roxin, Alex and Hakim, Vincent and Brunel, Nicolas}, Crdt = {2008/10/17 09:00}, Da = {20081016}, Date = {2008 Oct 15}, Date-Added = {2009-03-26 11:41:24 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081029}, Edat = {2008/10/17 09:00}, Ein = {J Neurosci. 2008 Oct 29;28(44):following 11431.}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Keywords = {21 Cortical oscillations; 21 Neurophysiology}, Language = {eng}, Lr = {20081030}, Mh = {*Cerebral Cortex/physiology; Databases, Factual/trends; *Neural Networks (Computer); *Neurons/physiology; Stochastic Processes}, Mhda = {2008/10/31 09:00}, Month = {Oct}, Number = {42}, Own = {NLM}, Pages = {10734--10745}, Pii = {28/42/10734}, Pl = {United States}, pmid = {18923048}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {The statistics of repeating patterns of cortical activity can be reproduced by a model network of stochastic binary neurons}, Volume = {28}, Year = {2008}, url = {papers/Roxin_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1016-08.2008}} @article{Ruthazer:2003, Abstract = {To determine how patterned visual activity regulates the development of axonal projections, we collected in vivo time-lapse images of retinal axons from albino Xenopus tadpoles in which binocular innervation of the optic tectum was induced. Axons added branch tips with nearly equal probability in all territories, but eliminated them preferentially from territory dominated by the opposite eye. This selective branch elimination was abolished by blockade of N-methyl-D-aspartate receptors. These results describe a correlation-based mechanism by which visual experience directly governs axon branch dynamics that contribute to the development of topographic maps.}, Address = {Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.}, Author = {Ruthazer, Edward S and Akerman, Colin J and Cline, Hollis T}, Crdt = {2003/07/05 05:00}, Da = {20030704}, Date = {2003 Jul 4}, Date-Added = {2009-03-26 11:41:24 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20030714}, Edat = {2003/07/05 05:00}, Issn = {1095-9203 (Electronic)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Axons/*physiology; Brain Mapping; Computer Simulation; Cues; Dizocilpine Maleate/pharmacology; Dominance, Ocular; Evoked Potentials, Visual; Excitatory Amino Acid Antagonists/pharmacology; Image Processing, Computer-Assisted; Receptors, N-Methyl-D-Aspartate/antagonists \& inhibitors/physiology; Retina/growth \& development; Retinal Ganglion Cells/cytology/*physiology; Superior Colliculi/anatomy \& histology/growth \& development/*physiology; Visual Pathways/growth \& development/*physiology; Xenopus laevis}, Mhda = {2003/07/15 05:00}, Month = {Jul}, Number = {5629}, Own = {NLM}, Pages = {66--70}, Pii = {301/5629/66}, Pl = {United States}, pmid = {12843386}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Excitatory Amino Acid Antagonists); 0 (Receptors, N-Methyl-D-Aspartate); 77086-22-7 (Dizocilpine Maleate)}, Sb = {IM}, Status = {MEDLINE}, Title = {Control of axon branch dynamics by correlated activity in vivo}, Volume = {301}, Year = {2003}, url = {papers/Ruthazer_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1082545}} @article{Hada:1999, Abstract = {PURPOSE: To evaluate the hypothesis that the expression of the calcium-binding protein parvalbumin (PV) in a subpopulation of gamma-aminobutyric acid (GABA)ergic neurons is an appropriate molecular marker for the effect on ocular dominance plasticity of monocular deprivation during the postnatal sensitive period. METHODS: Long-Evans rats underwent monocular enucleation immediately before eye opening (postnatal day [P] 14). Immunohistochemical analysis using anti-PV antibody was performed on the superior colliculus (SC) and lateral geniculate nucleus (LGN) at P45. In the visual cortex (VC) developmental changes in immunoreactivity were also examined at the ages of P17, P20, P27, and P45. Northern blot analysis for PV mRNA was also performed at P45. Changes in PV expression in the visual system of these rats were evaluated by use of a computer-based quantitative technique. RESULTS: PV-immunoreactive neurons were present in the SC and VC, whereas only a few were found in the LGN. The monocular enucleation at the onset of the sensitive period markedly reduced PV immunoreactivity in the neuropil of the SC, contralateral to the enucleated eye when examined one month later. No consistent and significant change in PV immunoreactivity was found in either the LGN or the VC. The number of PV-immunoreactive neurons in the VC rapidly decreased to the adult level during the middle of the sensitive period. The expression of PV mRNA in these central visual structures was not affected by early monocular enucleation. CONCLUSIONS: Expression of PV is developmentally regulated, and marked changes in its protein expression in the SC can be induced by monocular enucleation. Contrary to the original hypothesis, monocular enucleation did not consistently affect the expression of PV in the rat VC. The expression of PV is probably regulated by multiple factors, not merely by binocular competition.}, Address = {Department of Ophthalmology, Kobe University, School of Medicine, Hyogo, Japan.}, Author = {Hada, Y and Yamada, Y and Imamura, K and Mataga, N and Watanabe, Y and Yamamoto, M}, Crdt = {1999/10/06 00:00}, Da = {19991007}, Date = {1999 Oct}, Date-Added = {2009-03-26 11:37:20 -0400}, Date-Modified = {2009-03-26 11:38:24 -0400}, Dcom = {19991007}, Edat = {1999/10/06}, Issn = {0146-0404 (Print)}, Jid = {7703701}, Journal = {Invest Ophthalmol Vis Sci}, Jt = {Investigative ophthalmology \& visual science}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Blotting, Northern; *Eye Enucleation; *Gene Expression Regulation, Developmental; Geniculate Bodies/*growth \& development/metabolism; Immunoenzyme Techniques; Kainic Acid/pharmacology; Neurons/metabolism; Parvalbumins/*genetics/metabolism; RNA, Messenger/metabolism; Rats; Rats, Long-Evans; Superior Colliculi/*growth \& development/metabolism; Vision, Monocular/*genetics; Visual Cortex/*growth \& development/metabolism}, Mhda = {1999/10/06 00:01}, Month = {Oct}, Number = {11}, Own = {NLM}, Pages = {2535--2545}, Pl = {UNITED STATES}, pmid = {10509647}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {0 (Parvalbumins); 0 (RNA, Messenger); 487-79-6 (Kainic Acid)}, Sb = {IM}, Source = {Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2535-45.}, Status = {MEDLINE}, Title = {Effects of monocular enucleation on parvalbumin in rat visual system during postnatal development}, Volume = {40}, Year = {1999}, url = {papers/Hada_InvestOphthalmolVisSci1999.pdf}} @article{Morishita:2008, Abstract = {Neural circuits are shaped by experience in early postnatal life. The permanent loss of visual acuity (amblyopia) and anatomical remodeling within primary visual cortex following monocular deprivation is a classic example of critical period development from mouse to man. Recent work in rodents reveals a residual subthreshold potentiation of open eye response throughout life. Resetting excitatory-inhibitory balance or removing molecular 'brakes' on structural plasticity may unmask the potential for recovery of function in adulthood. Novel pharmacological or environmental interventions now hold great therapeutic promise based on a deeper understanding of critical period mechanisms.}, Address = {Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.}, Author = {Morishita, Hirofumi and Hensch, Takao K}, Crdt = {2008/06/07 09:00}, Da = {20080618}, Date = {2008 Feb}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Dcom = {20080930}, Dep = {20080603}, Edat = {2008/06/07 09:00}, Issn = {0959-4388 (Print)}, Jid = {9111376}, Journal = {Curr Opin Neurobiol}, Jt = {Current opinion in neurobiology}, Keywords = {21 Activity-development; 21 Neurophysiology; currOpinRvw}, Language = {eng}, Mh = {Aging/*genetics; Amblyopia/genetics; Animals; *Critical Period (Psychology); Humans; Mice; Models, Animal; Neuronal Plasticity/*genetics; Rats; Recovery of Function/genetics; Rodentia/genetics/growth \& development/metabolism; Sensory Deprivation/physiology; Visual Cortex/cytology/*growth \& development/metabolism; Visual Pathways/cytology/*growth \& development/metabolism}, Mhda = {2008/10/01 09:00}, Month = {Feb}, Number = {1}, Own = {NLM}, Pages = {101--107}, Phst = {2008/05/05 {$[$}received{$]$}; 2008/05/08 {$[$}accepted{$]$}; 2008/06/03 {$[$}aheadofprint{$]$}}, Pii = {S0959-4388(08)00037-8}, Pl = {England}, pmid = {18534841}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Review}, Rf = {73}, Sb = {IM}, Status = {MEDLINE}, Title = {Critical period revisited: impact on vision}, Volume = {18}, Year = {2008}, url = {papers/Morishita_CurrOpinNeurobiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2008.05.009}} @article{Huckfeldt:2009, Abstract = {Sensory neurons with common functions are often nonrandomly arranged and form dendritic territories that show little overlap, or tiling. Repulsive homotypic interactions underlie such patterns in cell organization in invertebrate neurons. It is unclear how dendro-dendritic repulsive interactions can produce a nonrandom distribution of cells and their spatial territories in mammalian retinal horizontal cells, as mature horizontal cell dendrites overlap substantially. By imaging developing mouse horizontal cells, we found that these cells transiently elaborate vertical neurites that form nonoverlapping columnar territories on reaching their final laminar positions. Targeted cell ablation revealed that the vertical neurites engage in homotypic interactions that result in tiling of neighboring cells before the establishment of their dendritic fields. This developmental tiling of transient neurites correlates with the emergence of a nonrandom distribution of the cells and could represent a mechanism that organizes neighbor relationships and territories of neurons before circuit assembly.}, Address = {Department of Biological Structure, University of Washington, 1959 NE Pacific Street, Seattle, Washington 98195, USA.}, Author = {Huckfeldt, Rachel M and Schubert, Timm and Morgan, Josh L and Godinho, Leanne and Di Cristo, Graziella and Huang, Z Josh and Wong, Rachel O L}, Crdt = {2008/12/09 09:00}, Da = {20081224}, Date = {2009 Jan}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090129}, Dep = {20081207}, Edat = {2008/12/09 09:00}, Gr = {EY17101/EY/NEI NIH HHS/United States}, Issn = {1546-1726 (Electronic)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Mh = {Aging; Animals; Animals, Newborn; Cell Communication/physiology; Cell Movement; Embryo, Mammalian; Green Fluorescent Proteins; Luminescent Agents; Mice; Neurites/*physiology/*ultrastructure; Retinal Horizontal Cells/cytology/*physiology/*ultrastructure; Time Factors}, Mhda = {2009/01/30 09:00}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {35--43}, Phst = {2008/09/24 {$[$}received{$]$}; 2008/11/05 {$[$}accepted{$]$}; 2008/12/07 {$[$}aheadofprint{$]$}}, Pii = {nn.2236}, Pl = {United States}, pmid = {19060895}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Rn = {0 (Luminescent Agents); 147336-22-9 (Green Fluorescent Proteins)}, Sb = {IM}, Status = {MEDLINE}, Title = {Transient neurites of retinal horizontal cells exhibit columnar tiling via homotypic interactions}, Volume = {12}, Year = {2009}, url = {papers/Huckfeldt_NatNeurosci2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2236}} @article{Niell:2005, Abstract = {The visual pathway from the retina to the optic tectum in fish and frogs has long been studied as a model for neural circuit formation. Although morphological aspects, such as axonal and dendritic arborization, have been well characterized, less is known about how this translates into functional properties of tectal neurons during development. We developed a system to provide controlled visual stimuli to larval zebrafish, while performing two-photon imaging of tectal neurons loaded with a fluorescent calcium indicator, allowing us to determine visual response properties in intact fish. In relatively mature larvae, we describe receptive field sizes, visual topography, and direction and size selectivity. We also characterize the onset and development of visual responses, beginning when retinal axons first arborize in the tectum. Surprisingly, most of these properties are established soon after dendrite growth and synaptogenesis begin and do not require patterned visual experience or a protracted period of refinement.}, Address = {Neutosciences Program, Department of Molecular and Cell Physiology, Stanford University, Stanford, California 94305, USA.}, Author = {Niell, Cristopher M and Smith, Stephen J}, Cin = {Neuron. 2005 Mar 24;45(6):825-8. PMID: 15797544}, Crdt = {2005/03/31 09:00}, Da = {20050330}, Date = {2005 Mar 24}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20050519}, Edat = {2005/03/31 09:00}, Gr = {NS043461/NS/NINDS NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Calcium imaging}, Language = {eng}, Lr = {20081121}, Mh = {Animals; Calcium Signaling/physiology; Cell Differentiation/*physiology; Dendrites/physiology/ultrastructure; Fluorescent Dyes; Growth Cones/physiology/ultrastructure; Image Cytometry/methods; Larva/anatomy \& histology/growth \& development; Microscopy, Fluorescence; Photic Stimulation; Retinal Ganglion Cells/cytology/*physiology; Superior Colliculi/cytology/growth \& development/*physiology; Synapses/physiology/ultrastructure; Time Factors; Vision, Ocular/*physiology; Visual Fields/physiology; Visual Pathways/cytology/growth \& development/*physiology; Zebrafish/anatomy \& histology/growth \& development/*physiology}, Mhda = {2005/05/20 09:00}, Month = {Mar}, Number = {6}, Own = {NLM}, Pages = {941--951}, Phst = {2004/09/09 {$[$}received{$]$}; 2004/12/20 {$[$}revised{$]$}; 2005/01/27 {$[$}accepted{$]$}}, Pii = {S0896-6273(05)00116-9}, Pl = {United States}, pmid = {15797554}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Fluorescent Dyes)}, Sb = {IM}, Status = {MEDLINE}, Title = {Functional imaging reveals rapid development of visual response properties in the zebrafish tectum}, Volume = {45}, Year = {2005}, url = {papers/Niell_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.01.047}} @article{Li:2008, Abstract = {The onset of vision occurs when neural circuits in the visual cortex are immature, lacking both the full complement of connections and the response selectivity that defines functional maturity. Direction-selective responses are particularly vulnerable to the effects of early visual deprivation, but it remains unclear how stimulus-driven neural activity guides the emergence of cortical direction selectivity. Here we report observations from a motion training protocol that allowed us to monitor the impact of experience on the development of direction-selective responses in visually naive ferrets. Using intrinsic signal imaging techniques, we found that training with a single axis of motion induced the rapid emergence of direction columns that were confined to cortical regions preferentially activated by the training stimulus. Using two-photon calcium imaging techniques, we found that single neurons in visually naive animals exhibited weak directional biases and lacked the strong local coherence in the spatial organization of direction preference that was evident in mature animals. Training with a moving stimulus, but not with a flashed stimulus, strengthened the direction-selective responses of individual neurons and preferentially reversed the direction biases of neurons that deviated from their neighbours. Both effects contributed to an increase in local coherence. We conclude that early experience with moving visual stimuli drives the rapid emergence of direction-selective responses in the visual cortex.}, Address = {Department of Neurobiology, Duke University School of Medicine, Durham, North Carolina 27710, USA.}, Author = {Li, Ye and Van Hooser, Stephen D and Mazurek, Mark and White, Leonard E and Fitzpatrick, David}, Crdt = {2008/10/24 09:00}, Da = {20081218}, Date = {2008 Dec 18}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090113}, Dep = {20081022}, Edat = {2008/10/24 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Calcium imaging}, Language = {eng}, Lr = {20090219}, Mh = {Animals; Calcium Signaling; Ferrets/growth \& development/*physiology; *Motion; Photic Stimulation; Photons; Visual Cortex/cytology/growth \& development/*physiology; Visual Perception/*physiology}, Mhda = {2009/01/14 09:00}, Mid = {NIHMS69455}, Month = {Dec}, Number = {7224}, Oid = {NLM: NIHMS69455 {$[$}Available on 06/18/09{$]$}; NLM: PMC2644578 {$[$}Available on 06/18/09{$]$}}, Own = {NLM}, Pages = {952--956}, Phst = {2008/05/08 {$[$}received{$]$}; 2008/09/11 {$[$}accepted{$]$}; 2008/10/22 {$[$}aheadofprint{$]$}}, Pii = {nature07417}, Pl = {England}, Pmc = {PMC2644578}, Pmcr = {2009/06/18}, pmid = {18946471}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Experience with moving visual stimuli drives the early development of cortical direction selectivity}, Volume = {456}, Year = {2008}, url = {papers/Li_Nature2008.pdf}, Bdsk-File-2 = {papers/Li_Nature2008a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07417}} @article{Garaschuk:2006a, Abstract = {The precise understanding of the cellular and molecular basis of brain function requires the direct assessment of the activity of defined cells in vivo. A promising approach for such analyses is two-photon microscopy in combination with appropriate cell labeling techniques. Here, we review the multi-cell bolus loading (MCBL) method that involves the use of membrane-permeant fluorescent indicator dyes. We show that this approach is useful for the functional analysis of clusters of neurons and glial cells in vivo. Work from our and other laboratories shows that the techniques that were previously feasible only in brain slices, like targeted patch clamp recordings from identified cells or pharmacological manipulations in confined brain regions, can now be used also in vivo. We also show that MCBL and two-photon imaging can be easily combined with other labeling techniques, particularly with those involving the use of genetically encoded, green-fluorescent-protein-based indicators. Finally, we examine recent applications of MCBL/two-photon imaging for the analysis of various brain regions, including the somatosensory and the visual cortex.}, Address = {Institut fur Neurowissenschaften, Technische Universitat Munchen, Biedersteinerstr. 29, 80802, Munich, Germany. arthur.konnerth@lrz.tum.de}, Author = {Garaschuk, Olga and Milos, Ruxandra-Iulia and Grienberger, Christine and Marandi, Nima and Adelsberger, Helmuth and Konnerth, Arthur}, Crdt = {2006/10/19 09:00}, Da = {20061119}, Date = {2006 Dec}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20071016}, Dep = {20061018}, Edat = {2006/10/19 09:00}, Issn = {0031-6768 (Print)}, Jid = {0154720}, Journal = {Pflugers Arch}, Jt = {Pflugers Archiv : European journal of physiology}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Calcium imaging}, Language = {eng}, Mh = {Action Potentials/physiology; Aging/physiology; Animals; Brain/cytology/*physiology; Calcium Signaling/physiology; Cats; Fluorescent Dyes/administration \& dosage; Mice; Microscopy, Fluorescence, Multiphoton; Nerve Net/cytology/*physiology; Neurons/cytology/*physiology; Patch-Clamp Techniques; Rats; Zebrafish}, Mhda = {2007/10/17 09:00}, Month = {Dec}, Number = {3}, Own = {NLM}, Pages = {385--396}, Phst = {2006/07/07 {$[$}received{$]$}; 2006/08/02 {$[$}accepted{$]$}; 2006/10/18 {$[$}aheadofprint{$]$}}, Pl = {Germany}, pmid = {17047983}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Review}, Rf = {49}, Rn = {0 (Fluorescent Dyes)}, Sb = {IM}, Status = {MEDLINE}, Title = {Optical monitoring of brain function in vivo: from neurons to networks}, Volume = {453}, Year = {2006}, url = {papers/Garaschuk_PflugersArch2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00424-006-0150-x}} @article{Nikolaev:2009, Abstract = {Naturally occurring axonal pruning and neuronal cell death help to sculpt neuronal connections during development, but their mechanistic basis remains poorly understood. Here we report that beta-amyloid precursor protein (APP) and death receptor 6 (DR6, also known as TNFRSF21) activate a widespread caspase-dependent self-destruction program. DR6 is broadly expressed by developing neurons, and is required for normal cell body death and axonal pruning both in vivo and after trophic-factor deprivation in vitro. Unlike neuronal cell body apoptosis, which requires caspase 3, we show that axonal degeneration requires caspase 6, which is activated in a punctate pattern that parallels the pattern of axonal fragmentation. DR6 is activated locally by an inactive surface ligand(s) that is released in an active form after trophic-factor deprivation, and we identify APP as a DR6 ligand. Trophic-factor deprivation triggers the shedding of surface APP in a beta-secretase (BACE)-dependent manner. Loss- and gain-of-function studies support a model in which a cleaved amino-terminal fragment of APP (N-APP) binds DR6 and triggers degeneration. Genetic support is provided by a common neuromuscular junction phenotype in mutant mice. Our results indicate that APP and DR6 are components of a neuronal self-destruction pathway, and suggest that an extracellular fragment of APP, acting via DR6 and caspase 6, contributes to Alzheimer's disease.}, Address = {Division of Research, Genentech, Inc., 1 DNA Way, South San Francisco, California 94080, USA.}, Author = {Nikolaev, Anatoly and McLaughlin, Todd and O'Leary, Dennis D M and Tessier-Lavigne, Marc}, Cin = {Nature. 2009 Feb 19;457(7232):970-1. PMID: 19225511}, Crdt = {2009/02/20 09:00}, Da = {20090219}, Date = {2009 Feb 19}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090324}, Edat = {2009/02/20 09:00}, Gr = {R01 EY07025/EY/NEI NIH HHS/United States}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {10 Structural plasticity}, Language = {eng}, Mh = {Alzheimer Disease/metabolism; Amyloid beta-Protein Precursor/chemistry/*metabolism; Animals; Axons/*metabolism; Caspase 3/metabolism; Caspase 6/*metabolism; Caspases/*metabolism; Cell Death; Ligands; Mice; Neurons/*cytology/*metabolism; Peptide Fragments/chemistry/metabolism; Protein Binding; Receptors, Tumor Necrosis Factor/*metabolism; Signal Transduction; bcl-2-Associated X Protein/genetics/metabolism}, Mhda = {2009/03/25 09:00}, Month = {Feb}, Number = {7232}, Own = {NLM}, Pages = {981--989}, Phst = {2008/05/24 {$[$}received{$]$}; 2008/12/31 {$[$}accepted{$]$}}, Pii = {nature07767}, Pl = {England}, pmid = {19225519}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Amyloid beta-Protein Precursor); 0 (Bax protein, mouse); 0 (Ligands); 0 (Peptide Fragments); 0 (Receptors, Tumor Necrosis Factor); 0 (Tnfrsf21 protein, mouse); 0 (bcl-2-Associated X Protein); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 6); EC 3.4.22.- (Caspases)}, Sb = {IM}, Status = {MEDLINE}, Title = {APP binds DR6 to trigger axon pruning and neuron death via distinct caspases}, Volume = {457}, Year = {2009}, url = {papers/Nikolaev_Nature2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07767}} @article{Peng:2009, Abstract = {Neural circuit development requires concurrent morphological and functional changes. Here, we identify coordinated and inversely correlated changes in dendritic morphology and mEPSC amplitude following increased neural activity. We show that overexpression of beta-catenin, a molecule that increases total dendritic length, mimics the effects of increased neuronal activity by scaling down mEPSC amplitudes, while postsynaptic expression of a protein that sequesters beta-catenin reverses the effects of activity on reducing mEPSC amplitudes. These results were confirmed immunocytochemically as changes in the size and density of surface synaptic AMPA receptor clusters. In individual neurons there was an inverse linear relationship between total dendritic length and average mEPSC amplitude. Importantly, beta-catenin overexpression in vivo promoted dendritic growth and reduced mEPSC amplitudes. Together, these results demonstrate that coordinated changes in dendritic morphology and unitary excitatory synaptic strength may serve as an important intrinsic mechanism that helps prevent neurons from overexcitation during neural circuit development.}, Address = {Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.}, Author = {Peng, Yi-Rong and He, Shan and Marie, Helene and Zeng, Si-Yu and Ma, Jun and Tan, Zhu-Jun and Lee, Soo Yeun and Malenka, Robert C and Yu, Xiang}, Crdt = {2009/01/17 09:00}, Da = {20090116}, Date = {2009 Jan 15}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20090205}, Edat = {2009/01/17 09:00}, Gr = {5 R37 MH063394/MH/NIMH NIH HHS/United States}, Issn = {1097-4199 (Electronic)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Mh = {Animals; Cadherins/metabolism; Cells, Cultured; *Dendrites/metabolism/ultrastructure; Excitatory Postsynaptic Potentials/physiology; Hippocampus/cytology/metabolism; Nerve Net/*physiology/ultrastructure; Neurons/cytology/drug effects/metabolism; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Receptors, AMPA/metabolism; Sodium Channel Blockers/pharmacology; *Synapses/metabolism/ultrastructure; Synaptic Transmission/drug effects/*physiology; Tetrodotoxin/pharmacology; beta Catenin/metabolism}, Mhda = {2009/02/06 09:00}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {71--84}, Phst = {2007/10/27 {$[$}received{$]$}; 2008/08/07 {$[$}revised{$]$}; 2008/11/10 {$[$}accepted{$]$}}, Pii = {S0896-6273(08)00969-0}, Pl = {United States}, pmid = {19146814}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't}, Rn = {0 (Cadherins); 0 (Receptors, AMPA); 0 (Sodium Channel Blockers); 0 (beta Catenin); 4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Status = {MEDLINE}, Title = {Coordinated changes in dendritic arborization and synaptic strength during neural circuit development}, Volume = {61}, Year = {2009}, url = {papers/Peng_Neuron2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.11.015}} @article{Keck:2008, Abstract = {The cerebral cortex has the ability to adapt to altered sensory inputs. In the visual cortex, a small lesion to the retina causes the deprived cortical region to become responsive to adjacent parts of the visual field. This extensive topographic remapping is assumed to be mediated by the rewiring of intracortical connections, but the dynamics of this reorganization process remain unknown. We used repeated intrinsic signal and two-photon imaging to monitor functional and structural alterations in adult mouse visual cortex over a period of months following a retinal lesion. The rate at which dendritic spines were lost and gained increased threefold after a small retinal lesion, leading to an almost complete replacement of spines in the deafferented cortex within 2 months. Because this massive remodeling of synaptic structures did not occur when all visual input was removed, it likely reflects the activity-dependent establishment of new cortical circuits that serve the recovery of visual responses.}, Address = {Max Planck Institute of Neurobiology, Am Klopfersptiz 18, D-82152 Martinsried, Germany.}, Author = {Keck, Tara and Mrsic-Flogel, Thomas D and Vaz Afonso, Miguel and Eysel, Ulf T and Bonhoeffer, Tobias and Hubener, Mark}, Crdt = {2008/09/02 09:00}, Da = {20080926}, Date = {2008 Oct}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081106}, Dep = {20080831}, Edat = {2008/09/02 09:00}, Issn = {1546-1726 (Electronic)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology; structural remodeling; Sensory Deprivation; visual cortex; visual system; topographic map; function; Mouse; multiphoton; microscopy; intrinsic signal}, Language = {eng}, Mh = {Analysis of Variance; Animals; Brain Mapping; Dendritic Spines; Image Processing, Computer-Assisted/methods; Magnetic Resonance Imaging/methods; Mice; Nerve Net/*physiology; Neuronal Plasticity/*physiology; Neurons/cytology/*physiology; Recovery of Function; Retina/injuries/physiology; Sensory Deprivation/physiology; Statistics, Nonparametric; Time Factors; Visual Cortex/*cytology/*physiology; Visual Fields/physiology; Visual Pathways/physiology}, Mhda = {2008/11/07 09:00}, Month = {Oct}, Number = {10}, Own = {NLM}, Pages = {1162--1167}, Phst = {2008/04/16 {$[$}received{$]$}; 2008/07/02 {$[$}accepted{$]$}; 2008/08/31 {$[$}aheadofprint{$]$}}, Pii = {nn.2181}, Pl = {United States}, pmid = {18758460}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {MEDLINE}, Title = {Massive restructuring of neuronal circuits during functional reorganization of adult visual cortex}, Volume = {11}, Year = {2008}, url = {papers/Keck_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2181}} @article{Kara:2009, Abstract = {In invertebrate predators such as the praying mantis and vertebrate predators such as wild cats the ability to detect small differences in inter-ocular retinal disparities is a critical means for accurately determining the depth of moving objects such as prey. In mammals, the first neurons along the visual pathway that encode binocular disparities are found in the visual cortex. However, a precise functional architecture for binocular disparity has never been demonstrated in any species, and coarse maps for disparity have been found in only one primate species. Moreover, the dominant approach for assaying the developmental plasticity of binocular cortical neurons used monocular tests of ocular dominance to infer binocular function. The few studies that examined the relationship between ocular dominance and binocular disparity of individual cells used single-unit recordings and have provided conflicting results regarding whether ocular dominance can predict the selectivity or sensitivity to binocular disparity. We used two-photon calcium imaging to sample the response to monocular and binocular visual stimuli from nearly every adjacent neuron in a small region of the cat visual cortex, area 18. Here we show that local circuits for ocular dominance always have smooth and graded transitions from one apparently monocular functional domain to an adjacent binocular region. Most unexpectedly, we discovered a new map in the cat visual cortex that had a precise functional micro-architecture for binocular disparity selectivity. At the level of single cells, ocular dominance was unrelated to binocular disparity selectivity or sensitivity. When the local maps for ocular dominance and binocular disparity both had measurable gradients at a given cortical site, the two gradient directions were orthogonal to each other. Together, these results indicate that, from the perspective of the spiking activity of individual neurons, ocular dominance cannot predict binocular disparity tuning. However, the precise local arrangement of ocular dominance and binocular disparity maps provide new clues regarding how monocular and binocular depth cues may be combined and decoded.}, Address = {Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA.}, Author = {Kara, P and Boyd, JD}, Crdt = {2009/01/23 09:00}, Da = {20090122}, Date = {2009 Jan 21}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-15 18:54:13 -0400}, Dep = {20090121}, Edat = {2009/01/23 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Calcium imaging; topographic map; sensory map; visual system; visual cortex; cat; optical physiology; multiphoton; Technique; Binocular; Monocular; bilateral; Sensory Deprivation}, Language = {ENG}, Mhda = {2009/01/23 09:00}, Month = {Jan}, Own = {NLM}, Phst = {2008/07/24 {$[$}received{$]$}; 2008/12/05 {$[$}accepted{$]$}; 2009/01/21 {$[$}aheadofprint{$]$}}, Pii = {nature07721}, pmid = {19158677}, Pst = {aheadofprint}, Pt = {JOURNAL ARTICLE}, Status = {Publisher}, Title = {A micro-architecture for binocular disparity and ocular dominance in visual cortex}, Year = {2009}, url = {papers/Kara_Nature2009.pdf}, Bdsk-File-2 = {papers/Kara_Nature2009a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07721}} @article{Niell:2004, Abstract = {The form of a neuron's dendritic arbor determines the set of axons with which it may form synaptic contacts, thus establishing connectivity within neural circuits. However, the dynamic relationship between dendrite growth and synaptogenesis is not well understood. To observe both processes simultaneously, we performed long-term imaging of non-spiny dendritic arbors expressing a fluorescent postsynaptic marker protein as they arborized within the optic tectum of live zebrafish larvae. Our results indicate that almost all synapses form initially on newly extended dendritic filopodia. A fraction of these nascent synapses are maintained, which in turn stabilizes the subset of filopodia on which they form. Stabilized filopodia mature into dendritic branches, and successive iterations of this process result in growth and branching of the arbor. These findings support a 'synaptotropic model' in which synapse formation can direct dendrite arborization.}, Address = {Neurosciences Program, Beckman Center, Stanford University, Stanford, California 94305, USA.}, Author = {Niell, Cristopher M and Meyer, Martin P and Smith, Stephen J}, Cin = {Nat Neurosci. 2004 Mar;7(3):205-6. PMID: 14983179}, Crdt = {2004/02/06 05:00}, Da = {20040225}, Date = {2004 Mar}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20040506}, Dep = {20040201}, Edat = {2004/02/06 05:00}, Gr = {NS043461/NS/NINDS NIH HHS/United States}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Biological Markers; Cell Communication/physiology; Cell Differentiation/*physiology; Dendrites/*metabolism/ultrastructure; Green Fluorescent Proteins; Luminescent Proteins; Molecular Sequence Data; Nerve Tissue Proteins/metabolism; Pseudopodia/metabolism/ultrastructure; Recombinant Fusion Proteins; Superior Colliculi/cytology/*embryology/metabolism; Synapses/*metabolism/ultrastructure; Synaptic Membranes/metabolism; Visual Pathways/cytology/embryology/metabolism; Zebrafish/*embryology/metabolism}, Mhda = {2004/05/07 05:00}, Month = {Mar}, Number = {3}, Own = {NLM}, Pages = {254--260}, Phst = {2003/11/04 {$[$}received{$]$}; 2004/01/14 {$[$}accepted{$]$}; 2004/02/01 {$[$}aheadofprint{$]$}}, Pii = {nn1191}, Pl = {United States}, pmid = {14758365}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Biological Markers); 0 (Luminescent Proteins); 0 (Nerve Tissue Proteins); 0 (Recombinant Fusion Proteins); 0 (postsynaptic density proteins); 147336-22-9 (Green Fluorescent Proteins)}, Sb = {IM}, Si = {GENBANK/AY520570}, Status = {MEDLINE}, Title = {In vivo imaging of synapse formation on a growing dendritic arbor}, Volume = {7}, Year = {2004}, url = {papers/Niell_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1191}} @article{Sumbre:2008, Abstract = {The ability to process temporal information is fundamental to sensory perception, cognitive processing and motor behaviour of all living organisms, from amoebae to humans. Neural circuit mechanisms based on neuronal and synaptic properties have been shown to process temporal information over the range of tens of microseconds to hundreds of milliseconds. How neural circuits process temporal information in the range of seconds to minutes is much less understood. Studies of working memory in monkeys and rats have shown that neurons in the prefrontal cortex, the parietal cortex and the thalamus exhibit ramping activities that linearly correlate with the lapse of time until the end of a specific time interval of several seconds that the animal is trained to memorize. Many organisms can also memorize the time interval of rhythmic sensory stimuli in the timescale of seconds and can coordinate motor behaviour accordingly, for example, by keeping the rhythm after exposure to the beat of music. Here we report a form of rhythmic activity among specific neuronal ensembles in the zebrafish optic tectum, which retains the memory of the time interval (in the order of seconds) of repetitive sensory stimuli for a duration of up to approximately 20 s. After repetitive visual conditioning stimulation (CS) of zebrafish larvae, we observed rhythmic post-CS activities among specific tectal neuronal ensembles, with a regular interval that closely matched the CS. Visuomotor behaviour of the zebrafish larvae also showed regular post-CS repetitions at the entrained time interval that correlated with rhythmic neuronal ensemble activities in the tectum. Thus, rhythmic activities among specific neuronal ensembles may act as an adjustable 'metronome' for time intervals in the order of seconds, and serve as a mechanism for the short-term perceptual memory of rhythmic sensory experience.}, Address = {Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720, USA.}, Author = {Sumbre, German and Muto, Akira and Baier, Herwig and Poo, Mu-ming}, Crdt = {2008/10/17 09:00}, Da = {20081106}, Date = {2008 Nov 6}, Date-Added = {2009-03-26 11:32:27 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20081204}, Dep = {20081015}, Edat = {2008/10/17 09:00}, Issn = {1476-4687 (Electronic)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Keywords = {21 Activity-development; 21 Neurophysiology; 21 Calcium imaging; entrainment;Zebrafish;calcium imaging;multiphoton;microscopy;behavior}, Language = {eng}, Mh = {Animals; Calcium/metabolism; Conditioning (Psychology); Larva/physiology; Memory/*physiology; Neurons/*physiology; *Periodicity; Photic Stimulation; Superior Colliculi/cytology/physiology; Swimming/physiology; Tail/physiology; Time Factors; Zebrafish/embryology/growth \& development/*physiology}, Mhda = {2008/12/17 09:00}, Month = {Nov}, Number = {7218}, Own = {NLM}, Pages = {102--106}, Phst = {2008/04/14 {$[$}received{$]$}; 2008/08/20 {$[$}accepted{$]$}; 2008/10/15 {$[$}aheadofprint{$]$}}, Pii = {nature07351}, Pl = {England}, pmid = {18923391}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Rn = {7440-70-2 (Calcium)}, Sb = {IM}, Status = {MEDLINE}, Title = {Entrained rhythmic activities of neuronal ensembles as perceptual memory of time interval}, Volume = {456}, Year = {2008}, url = {papers/Sumbre_Nature2008.pdf}, Bdsk-File-2 = {papers/Sumbre_Nature2008a.pdf}, Bdsk-File-3 = {papers/Sumbre_Nature2008.avi}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07351}} @article{Zheng:1999, Abstract = {The external nucleus of the inferior colliculus in the barn owl contains an auditory map of space that is based on the tuning of neurons for interaural differences in the timing of sound. In juvenile owls, this region of the brain can acquire alternative maps of interaural time difference as a result of abnormal experience. It has been found that, in an external nucleus that is expressing a learned, abnormal map, the circuitry underlying the normal map still exists but is functionally inactivated by inhibition mediated by gamma-aminobutyric acid type A (GABAA) receptors. This inactivation results from disproportionately strong inhibition of specific input channels to the network. Thus, experience-driven changes in patterns of inhibition, as well as adjustments in patterns of excitation, can contribute critically to adaptive plasticity in the central nervous system.}, Address = {Department of Neurobiology, Fairchild Science Building, Stanford University School of Medicine, Stanford, CA 94305-5125, USA. Weimin@barnowl.stanford.edu}, Author = {Zheng, W and Knudsen, E I}, Cin = {Science. 1999 May 7;284(5416):925-6. PMID: 10357679}, Crdt = {1999/05/13 00:00}, Da = {19990603}, Date = {1999 May 7}, Date-Added = {2009-03-26 11:28:24 -0400}, Date-Modified = {2009-03-26 11:29:28 -0400}, Dcom = {19990603}, Edat = {1999/05/13}, Gr = {5 R01 DC00155-18/DC/NIDCD NIH HHS/United States; F32 DC00307-01/DC/NIDCD NIH HHS/United States}, Issn = {0036-8075 (Print)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Keywords = {21 Activity-development; 21 Neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Acoustic Stimulation; Animals; Auditory Pathways/*physiology; Bicuculline/analogs \& derivatives/pharmacology; Brain Mapping; Cues; Inferior Colliculi/*physiology; Learning; Nerve Net/physiology; Neural Inhibition; *Neuronal Plasticity; Photic Stimulation; Receptors, GABA-A/antagonists \& inhibitors/*physiology; Sound Localization; Strigiformes/*physiology; Superior Colliculi/physiology; Visual Fields; Visual Pathways/*physiology}, Mhda = {1999/05/13 00:01}, Month = {May}, Number = {5416}, Own = {NLM}, Pages = {962--965}, Pl = {UNITED STATES}, pmid = {10320376}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Receptors, GABA-A); 40709-69-1 (bicuculline methiodide); 485-49-4 (Bicuculline)}, Sb = {IM}, Status = {MEDLINE}, Title = {Functional selection of adaptive auditory space map by GABAA-mediated inhibition}, Volume = {284}, Year = {1999}, url = {papers/Zheng_Science1999.pdf}} @article{Linkenhoker:2005, Abstract = {Early experience plays a powerful role in shaping adult neural circuitry and behavior. In barn owls, early experience markedly influences sound localization. Juvenile owls that learn new, abnormal associations between auditory cues and locations in visual space as a result of abnormal visual experience can readapt to the same abnormal experience in adulthood, when plasticity is otherwise limited. Here we show that abnormal anatomical projections acquired during early abnormal sensory experience persist long after normal experience has been restored. These persistent projections are perfectly situated to provide a physical framework for subsequent readaptation in adulthood to the abnormal sensory conditions experienced in early life. Our results show that anatomical changes that support strong learned neural connections early in life can persist even after they are no longer functionally expressed. This maintenance of silenced neural circuitry that was once adaptive may represent an important mechanism by which the brain preserves a record of early experience.}, Address = {Department of Neurobiology, Fairchild Science Building, Stanford University School of Medicine, Stanford, California 94305, USA.}, Author = {Linkenhoker, Brie Ann and von der Ohe, Christina G and Knudsen, Eric I}, Crdt = {2004/12/21 09:00}, Da = {20041228}, Date = {2005 Jan}, Date-Added = {2009-03-26 11:09:48 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20050302}, Dep = {20041219}, Edat = {2004/12/21 09:00}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Auditory Pathways/anatomy \& histology/*growth \& development/physiology/ultrastructure; Brain Mapping; Cues; Ear/physiology; Electrophysiology; Eyeglasses; Hearing; Inferior Colliculi/growth \& development; *Learning; Neuronal Plasticity; Presynaptic Terminals/ultrastructure; *Sound Localization; Strigiformes/*growth \& development; Superior Colliculi/growth \& development; Synaptic Transmission; Time Factors}, Mhda = {2005/03/03 09:00}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {93--98}, Phst = {2004/04/21 {$[$}received{$]$}; 2004/09/13 {$[$}accepted{$]$}; 2004/12/19 {$[$}aheadofprint{$]$}}, Pii = {nn1367}, Pl = {United States}, pmid = {15608636}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Anatomical traces of juvenile learning in the auditory system of adult barn owls}, Volume = {8}, Year = {2005}, url = {papers/Linkenhoker_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1367}} @article{Sur:1990, Abstract = {Early developmental manipulations can induce sensory afferents of one modality to project to central targets of a different sensory modality. We and other investigators have used such cross-modal plasticity to examine the role of afferent inputs and their patterns of activity in the development of sensory neocortex. We suggest that the afferent rewiring can significantly influence the internal connectivity or microcircuitry of sensory cortex, aspects of which appear to be determined or specified relatively late in development, but that they cannot influence, or influence only to a minor extent, the laminar characteristics and external connectivity patterns of cortex, which appear to be specified earlier.}, Address = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.}, Author = {Sur, M and Pallas, S L and Roe, A W}, Crdt = {1990/06/01 00:00}, Da = {19900801}, Date = {1990 Jun}, Date-Added = {2009-03-26 10:57:53 -0400}, Date-Modified = {2009-03-26 11:01:54 -0400}, Dcom = {19900801}, Edat = {1990/06/01}, Issn = {0166-2236 (Print)}, Jid = {7808616}, Journal = {Trends Neurosci}, Jt = {Trends in neurosciences}, Keywords = {21 Activity-development}, Language = {eng}, Lr = {20061115}, Mh = {Animals; Cerebral Cortex/*growth \& development/physiology; *Neuronal Plasticity; Visual Cortex/growth \& development/physiology}, Mhda = {1990/06/01 00:01}, Month = {Jun}, Number = {6}, Own = {NLM}, Pages = {227--233}, Pii = {0166-2236(90)90165-7}, Pl = {ENGLAND}, pmid = {1694329}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {60}, Sb = {IM}, Status = {MEDLINE}, Title = {Cross-modal plasticity in cortical development: differentiation and specification of sensory neocortex}, Volume = {13}, Year = {1990}, url = {papers/Sur_TrendsNeurosci1990.pdf}} @article{Greenberg:2009, Abstract = {Two-photon imaging of bulk-loaded calcium dyes can record action potentials (APs) simultaneously from dozens of spatially resolved neurons in vivo. Extending this technique to awake animals, however, has remained technically challenging due to artifacts caused by brain motion. Since in two-photon excitation microscopes image pixels are captured sequentially by scanning a focused pulsed laser across small areas of interest within the brain, fast displacements of the imaged area can distort the image nonuniformly. If left uncorrected, brain motion in awake animals will cause artifactual fluorescence changes, masking the small functional fluorescence increases associated with AP discharge. We therefore present a procedure for detection and correction of both fast and slow displacements in two-photon imaging of awake animals. Our algorithm, based on the Lucas-Kanade framework, operates directly on the motion-distorted imaging data, requiring neither external signals such as heartbeat nor a distortion-free template image. Motion correction accuracy was tested in silico over a wide range of simplified and realistic displacement trajectories and for multiple levels of fluorescence noise. Accuracy was confirmed in vivo by comparing solutions obtained from red and green fluorophores imaged simultaneously. Finally, the accuracy of AP detection from motion-displaced bulk-loaded calcium imaging is evaluated with and without motion correction, and we conclude that accurate motion correction as achieved by this procedure is both necessary and sufficient for single AP detection in awake animals.}, Address = {Network Imaging Group, Max Planck Institute for Biological Cybernetics, Spemannstrasse 41, 72076 Tubingen, Germany. david@tuebingen.mpg.de}, Author = {Greenberg, David S and Kerr, Jason N D}, Crdt = {2008/09/16 09:00}, Da = {20081028}, Date = {2009 Jan 15}, Date-Added = {2009-03-25 23:29:41 -0400}, Date-Modified = {2012-04-13 18:39:07 +0000}, Dep = {20080826}, Edat = {2008/09/16 09:00}, Issn = {0165-0270 (Print)}, Jid = {7905558}, Journal = {J Neurosci Methods}, Jt = {Journal of neuroscience methods}, Keywords = {21 Calcium imaging}, Language = {eng}, Mhda = {2008/09/16 09:00}, Month = {Jan}, Number = {1}, Own = {NLM}, Pages = {1-15}, Phst = {2008/04/17 {$[$}received{$]$}; 2008/08/11 {$[$}revised{$]$}; 2008/08/12 {$[$}accepted{$]$}; 2008/08/26 {$[$}aheadofprint{$]$}}, Pii = {S0165-0270(08)00491-3}, Pl = {Netherlands}, pmid = {18789968}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Sb = {IM}, Status = {In-Process}, Title = {Automated correction of fast motion artifacts for two-photon imaging of awake animals}, Volume = {176}, Year = {2009}, url = {papers/Greenberg_JNeurosciMethods2009.pdf}, Bdsk-File-2 = {papers/Greenberg_JNeurosciMethods2009a.pdf}, Bdsk-File-3 = {papers/Greenberg_JNeurosciMethods2009.eps}, Bdsk-File-4 = {papers/Greenberg_JNeurosciMethods2009a.eps}, Bdsk-File-5 = {papers/Greenberg_JNeurosciMethods2009b.eps}, Bdsk-File-6 = {papers/Greenberg_JNeurosciMethods2009c.eps}, Bdsk-File-7 = {papers/Greenberg_JNeurosciMethods2009.mov}, Bdsk-File-8 = {papers/Greenberg_JNeurosciMethods2009a.mov}, Bdsk-File-9 = {papers/Greenberg_JNeurosciMethods2009b.mov}, File0 = {papers/Greenberg_JNeurosciMethods2009c.mov}, File1 = {papers/Greenberg_JNeurosciMethods2009d.mov}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2008.08.020}} @article{Udin:1988, Abstract = {The catalogue of data presented here form many systems demonstrates that multiple mechanisms are involved in the formation of topographic maps. We are not yet in a position to explain why a particular mechanism appears to dominate in some situations and not in others. Certain generalizations can be made, however. First, at least some form of chemospecificity can be invoked to help explain connectivity in all of the experiments we have cited. Often, the differential identities of a population of neurons can be reflected in an orderly pattern of axon outgrowth and in the actively maintained preservation of neighbor relations as the axons grow toward their targets; such orderly arrangements are not obligatory, but, where present, they facilitate the speedy establishment of orderly maps when the axons reach their target nuclei. Within a terminal zone, chemospecific cues may dominate and constrain a given axon to terminate in a specific location, but axon-axon interactions commonly supercede chemospecific matching. At least two forms of axon-axon interaction occur, one based on some sort of biochemical properties related to the axon's embryological identity and another based on the axons' electrical activity. Tasks for the future are to identify the cellular bases of each of these mechanisms and to understand the situations in which each is manifested.}, Address = {Department of Physiology, State University of New York, Buffalo 14214.}, Author = {Udin, S B and Fawcett, J W}, Crdt = {1988/01/01 00:00}, Da = {19880607}, Date = {1988}, Date-Added = {2009-03-25 23:28:13 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {19880607}, Edat = {1988/01/01}, Issn = {0147-006X (Print)}, Jid = {7804039}, Journal = {Annu Rev Neurosci}, Jt = {Annual review of neuroscience}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Auditory Pathways/anatomy \& histology/physiology; *Brain Mapping; Geniculate Bodies/*anatomy \& histology/cytology/physiology; Neuronal Plasticity; Retina/*anatomy \& histology/cytology/physiology; Superior Colliculi/*anatomy \& histology/cytology/physiology; Visual Pathways/*anatomy \& histology/physiology}, Mhda = {1988/01/01 00:01}, Own = {NLM}, Pages = {289--327}, Pl = {UNITED STATES}, pmid = {3284443}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {114}, Sb = {IM}, Source = {Annu Rev Neurosci. 1988;11:289-327.}, Status = {MEDLINE}, Title = {Formation of topographic maps}, Volume = {11}, Year = {1988}, url = {papers/Udin_AnnuRevNeurosci1988.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.ne.11.030188.001445}} @article{Vidyasagar:1978, Author = {Vidyasagar, T R}, Crdt = {1978/09/14 00:00}, Da = {19781202}, Date = {1978 Sep 14}, Date-Added = {2009-03-25 23:25:50 -0400}, Date-Modified = {2009-03-25 23:25:50 -0400}, Dcom = {19781202}, Edat = {1978/09/14}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Darkness; Rats/*physiology; Superior Colliculi/cytology/*growth \& development; Visual Pathways/growth \& development}, Mhda = {1978/09/14 00:01}, Month = {Sep}, Number = {5676}, Own = {NLM}, Pages = {140--141}, Pl = {ENGLAND}, pmid = {692682}, Pst = {ppublish}, Pt = {Journal Article}, Sb = {IM}, Status = {MEDLINE}, Title = {Possible plasticity in the rat superior colliculus}, Volume = {275}, Year = {1978}, url = {papers/Vidyasagar_Nature1978.pdf}} @article{Zhang:1998, Abstract = {In the developing frog visual system, topographic refinement of the retinotectal projection depends on electrical activity. In vivo whole-cell recording from developing Xenopus tectal neurons shows that convergent retinotectal synapses undergo activity-dependent cooperation and competition following correlated pre- and postsynaptic spiking within a narrow time window. Synaptic inputs activated repetitively within 20 ms before spiking of the tectal neuron become potentiated, whereas subthreshold inputs activated within 20 ms after spiking become depressed. Thus both the initial synaptic strength and the temporal order of activation are critical for heterosynaptic interactions among convergent synaptic inputs during activity-dependent refinement of developing neural networks.}, Address = {Department of Biology, University of California at San Diego, La Jolla 92093-0357, USA.}, Author = {Zhang, L I and Tao, H W and Holt, C E and Harris, W A and Poo, M}, Crdt = {1998/09/17 02:02}, Da = {19980928}, Date = {1998 Sep 3}, Date-Added = {2009-03-25 23:24:53 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {19980928}, Edat = {1998/09/17 02:02}, Issn = {0028-0836 (Print)}, Jid = {0410462}, Journal = {Nature}, Jt = {Nature}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Brain/embryology/physiology; Excitatory Postsynaptic Potentials; Retina/embryology/*physiology; Superior Colliculi/embryology/*physiology; Synapses/*physiology; Xenopus laevis}, Mhda = {2001/03/23 10:01}, Month = {Sep}, Number = {6697}, Own = {NLM}, Pages = {37--44}, Pl = {ENGLAND}, pmid = {9738497}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Source = {Nature. 1998 Sep 3;395(6697):37-44.}, Status = {MEDLINE}, Title = {A critical window for cooperation and competition among developing retinotectal synapses}, Volume = {395}, Year = {1998}, url = {papers/Zhang_Nature1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/25665}} @article{Nakatani:2007, Abstract = {The mechanism underlying the determination of neurotransmitter phenotype in the developing mesencephalon, particularly GABAergic versus glutamatergic fate, remains largely unknown. Here, we show in mice that the basic helix-loop-helix transcriptional repressor gene Helt (also known as Megane and Heslike) functions as a selector gene that determines GABAergic over glutamatergic fate in the mesencephalon. Helt was coincidently expressed in all the progenitor domains for mesencephalic GABAergic neurons. In the mesencephalon of Helt-deficient embryos, GABAergic neurons were mostly absent and glutamatergic neurons emerged instead. Conversely, ectopically expressed Helt suppressed glutamatergic formation and induced GABAergic neurogenesis. However, the Helt mutants showed normal progenitor domain formation. In consequence, postmitotic expression of the homeodomain factor Nkx2.2, which was specifically expressed by GABAergic populations in wild-type embryos, was maintained despite the transmitter phenotype conversion from GABAergic to glutamatergic in the Helt mutants, suggesting that Helt is not involved in neuronal identity specification. Furthermore, we identified proneural genes Ngn1 and Ngn2, which were selectively expressed in glutamatergic progenitors in the developing mesencephalon and had the ability to confer the glutamatergic fate, as downstream target genes of Helt. These results suggest that Helt determines GABAergic over glutamatergic fate, at least in part, by repressing Ngn (Neurog) genes and that basic helix-loop-helix transcription factor networks involving Helt and Ngns are commonly used in the mesencephalon for determination of the GABAergic versus glutamatergic transmitter phenotype.}, Address = {KAN Research Institute Inc., KobeMI R\&D Center, 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.}, Author = {Nakatani, Tomoya and Minaki, Yasuko and Kumai, Minoru and Ono, Yuichi}, Crdt = {2007/07/06 09:00}, Da = {20070711}, Date = {2007 Aug}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20070928}, Dep = {20070704}, Edat = {2007/07/06 09:00}, Issn = {0950-1991 (Print)}, Jid = {8701744}, Journal = {Development}, Jt = {Development (Cambridge, England)}, Language = {eng}, Mh = {Animals; Basic Helix-Loop-Helix Transcription Factors/*genetics/*physiology; Cell Differentiation/genetics; Down-Regulation; Gene Expression Regulation, Developmental; Glutamic Acid/*metabolism; Mesencephalon/cytology/*embryology/metabolism; Mice; Mice, Inbred C57BL; Mice, Knockout; Models, Biological; Nerve Tissue Proteins/*genetics/physiology; Neurons/*cytology/metabolism; Organ Specificity/genetics; Repressor Proteins/genetics/*physiology; Stem Cells/cytology; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2007/09/29 09:00}, Month = {Aug}, Number = {15}, Own = {NLM}, Pages = {2783--2793}, Phst = {2007/07/04 {$[$}aheadofprint{$]$}}, Pii = {dev.02870}, Pl = {England}, pmid = {17611227}, Pst = {ppublish}, Pt = {Journal Article}, Rn = {0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Helt protein, mouse); 0 (Nerve Tissue Proteins); 0 (Neurog2 protein, mouse); 0 (Repressor Proteins); 182238-50-2 (Neurog1 protein, mouse); 56-12-2 (gamma-Aminobutyric Acid); 56-86-0 (Glutamic Acid)}, Sb = {IM}, Status = {MEDLINE}, Title = {Helt determines GABAergic over glutamatergic neuronal fate by repressing Ngn genes in the developing mesencephalon}, Volume = {134}, Year = {2007}, url = {papers/Nakatani_Development2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.02870}} @article{Tsunekawa:2005, Abstract = {The superior colliculus (SC) is a layered structure in the midbrain and is particularly rich in gamma-aminobutyric acid (GABA). The present investigation aimed to determine whether the development of GABAergic neurons in the SC is common to that of the neocortex in which they are produced in a distinct area called the ganglionic eminence and are transported by tangential migration. A green fluorescent protein (GFP) knock-in mouse was used in which a GFP gene was introduced into the gene for glutamic acid decarboxylase (GAD) 67 and all GABAergic neurons were fluorescent. At embryonic day (E) 11-14, GFP-positive cells increased strikingly. They were spindle-shaped with processes at both poles and oriented radially between the ventricular and pial surface, together with other GFP-negative cells. After the cutting of the embryonic SC, GFP-positive cells accumulated on one side of the injury as expected from their radial but not tangential migration. In the living slice preparations GFP-positive cells migrated radially during the observation. These results indicate that tangential migration of GABAergic neurons as observed in the neocortex is not applicable and that radial migration from the underlying ventricular zone is predominant in the SC. At E12-13, bundles of commissural GFP-positive fibers which appeared to originate outside the SC were distributed at the superficial layer. These superficial fibers were no longer observed at the later stages.}, Address = {Laboratory of Neurochemistry, National Institute for Physiological Sciences and Graduate University for Advanced Studies, Okazaki 444-8585, Japan. tsunekaw@brain.riken.jp}, Author = {Tsunekawa, Naoko and Yanagawa, Yuchio and Obata, Kunihiko}, Crdt = {2005/02/16 09:00}, Da = {20050215}, Date = {2005 Mar}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20050509}, Dep = {20050107}, Edat = {2005/02/16 09:00}, Issn = {0168-0102 (Print)}, Jid = {8500749}, Journal = {Neurosci Res}, Jt = {Neuroscience research}, Language = {eng}, Lr = {20071115}, Mh = {Amino Acids/metabolism; Animals; Animals, Newborn; Cell Count/methods; Cell Growth Processes/physiology; DNA-Binding Proteins/metabolism; Drosophila Proteins/metabolism; Embryo, Mammalian; Female; Glutamate Decarboxylase/metabolism; Green Fluorescent Proteins/genetics/metabolism; Immunohistochemistry/methods; Isoenzymes/metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neural Pathways/growth \& development/metabolism; Neurofilament Proteins/metabolism; Neurons/*metabolism/physiology; Pregnancy; Superior Colliculi/*cytology/enzymology/growth \& development; Time Factors; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2005/05/10 09:00}, Month = {Mar}, Number = {3}, Own = {NLM}, Pages = {243--251}, Phst = {2004/08/04 {$[$}received{$]$}; 2004/11/19 {$[$}revised{$]$}; 2004/11/24 {$[$}accepted{$]$}; 2005/01/07 {$[$}aheadofprint{$]$}}, Pii = {S0168-0102(04)00299-8}, Pl = {Ireland}, pmid = {15710488}, Pst = {ppublish}, Pt = {Comparative Study; In Vitro; Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Amino Acids); 0 (Bearded protein, Drosophila); 0 (DNA-Binding Proteins); 0 (Drosophila Proteins); 0 (Isoenzymes); 0 (Neurofilament Proteins); 0 (dolaisoleucine); 147336-22-9 (Green Fluorescent Proteins); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 1)}, Sb = {IM}, Status = {MEDLINE}, Title = {Development of GABAergic neurons from the ventricular zone in the superior colliculus of the mouse}, Volume = {51}, Year = {2005}, url = {papers/Tsunekawa_NeurosciRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neures.2004.11.011}} @article{Chandrasekaran:2009, Abstract = {Gradients of molecular factors pattern the developing retina and superior colliculus (SC) and guide retinal ganglion cell (RGC) axons to their appropriate central target perinatally. During and subsequent to this period, spontaneous waves of action potentials sweep across the retina, providing an instructive topographic signal based on the correlations of firing patterns of neighbouring RGCs. How these activity-independent and activity-dependent factors interact during retinotopic map formation remains unclear. A typical phenotype of mutant mice lacking genes for one or more RGC axon guidance molecules is the presence of topographically inappropriate projections or 'ectopic spots'. Here, we examine mice that lack functional bone morphogenetic protein receptors (BMPRs) in the retina. Retinal BMP controls the graded expression of RGC axon guidance molecules, resulting in some dorsal RGCs projecting ectopically to locations in the SC that normally receive input from ventral retina. We examine the consequences of this anatomical phenotype in vivo by studying the receptive field (RF) properties of neurons in the superficial SC. We observe a mixture of physiological phenotypes in BMPR mutant mice; notably we find some neurons with ectopic RFs displaced in elevation, corresponding to the observed anatomical defect. However, in a result not necessarily congruent with the presence of focal ectopic projections, some neurons have split, enlarged and patchy/distorted RFs. These results are consistent with the effects of spontaneous retinal waves acting upon a disrupted molecular template, and they place significant limits on the form of an activity-dependent learning rule for the development of retinocollicular projections.}, Address = {Graduate Program in Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.}, Author = {Chandrasekaran, Anand R and Furuta, Yas and Crair, Michael C}, Crdt = {2009/01/21 09:00}, Da = {20090302}, Date = {2009 Mar 1}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Dep = {20090119}, Edat = {2009/01/21 09:00}, Gr = {P30 EY000785/EY/NEI NIH HHS/United States; R01 EY015788/EY/NEI NIH HHS/United States; R01 MH062639/MH/NIMH NIH HHS/United States}, Issn = {1469-7793 (Electronic)}, Jid = {0266262}, Journal = {J Physiol}, Jt = {The Journal of physiology}, Keywords = {21 Activity-development; currOpinRvw}, Language = {eng}, Mhda = {2009/01/21 09:00}, Month = {Mar}, Number = {Pt 5}, Own = {NLM}, Pages = {953--963}, Phst = {2009/01/19 {$[$}aheadofprint{$]$}}, Pii = {jphysiol.2008.160952}, Pl = {England}, pmid = {19153163}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural}, Sb = {IM}, Status = {In-Process}, Title = {Consequences of axon guidance defects on the development of retinotopic receptive fields in the mouse colliculus}, Volume = {587}, Year = {2009}, url = {papers/Chandrasekaran_JPhysiol2009.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2008.160952}} @article{Norgren:1998, Abstract = {Determining the connections of neural systems is critical for determining how they function. In this review, we focus on the use of HSV-1 and HSV-2 as transneuronal tracers. Using HSV to examine neural circuits is technically simple. HSV is injected into the area of interest, and after several days, the animals are perfused and processed for immunohistochemistry with antibodies to HSV proteins. Variables which influence HSV infection include species of host, age of host, titre of virus, strain of virus and phenotype of infected cell. The choice of strain of HSV is critically important. Several strains of HSV-1 and HSV-2 have been utilized for purposes of transneuronal tract-tracing. HSV has been used successfully to study neuronal circuitry in a variety of different neuroanatomical systems including the somatosensory, olfactory, visual, motor, autonomic and limbic systems.}, Address = {Department of Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha 68198, USA.}, Author = {Norgren, R B Jr and Lehman, M N}, Crdt = {1998/11/11 03:02}, Da = {19990126}, Date = {1998 Oct}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2009-03-25 23:16:15 -0400}, Dcom = {19990126}, Edat = {1998/11/11 03:02}, Issn = {0149-7634 (Print)}, Jid = {7806090}, Journal = {Neurosci Biobehav Rev}, Jt = {Neuroscience and biobehavioral reviews}, Language = {eng}, Lr = {20051116}, Mh = {Animals; Central Nervous System/cytology/physiology/*virology; Humans; Nerve Net/physiology/*virology; Neural Pathways/cytology/physiology/virology; Neurons/cytology/physiology/*virology; Neurophysiology/methods; Simplexvirus/*physiology}, Mhda = {2001/03/28 10:01}, Month = {Oct}, Number = {6}, Own = {NLM}, Pages = {695--708}, Pii = {S0149763498000086}, Pl = {UNITED STATES}, pmid = {9809305}, Pst = {ppublish}, Pt = {Journal Article; Review}, Rf = {167}, Sb = {IM}, Status = {MEDLINE}, Title = {Herpes simplex virus as a transneuronal tracer}, Volume = {22}, Year = {1998}, url = {papers/Norgren_NeurosciBiobehavRev1998.pdf}} @article{Razak:2003, Abstract = {Neonatal brain injury triggers compensatory processes that can be adaptive or detrimental, but little is known about the mechanisms of compensation or how they might affect the response properties of neurons within the injured region. We have studied this issue in a rodent model. Partial ablation of the hamster superior colliculus (SC) at birth results in a compressed but complete visual field map in the remaining SC and a compensatory conservation of receptive field (RF) size and stimulus velocity and size tuning. The circuit underlying stimulus tuning in this system or its preservation after brain lesions is not known. Our previous work has shown that N-methyl-d-aspartate (NMDA) receptors are necessary for the development and conservation of RF size after partial SC ablation. In this study, we examined whether NMDA receptor function is also necessary for the development and conservation of stimulus velocity and size tuning. We found that velocity and size tuning were unaffected by chronic postnatal blockade of NMDA receptors and the resulting increases in RF size. Thus NMDA receptors in the SC are not necessary for the development of stimulus velocity and size tuning or in the compensatory maintenance of these properties following brain damage. These results suggest that stimulus velocity and size tuning may arise in the retina or from NMDA receptor-independent circuitry intrinsic to SC. The lack of conflict between NMDA receptor activity-dependent and -independent processes may allow conservation of some RF properties while others change during injury-induced or evolutionary changes in afferent/target convergence.}, Address = {Graduate Program in Neurobiology and Behavior, Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.}, Author = {Razak, Khaleel A and Huang, Lihua and Pallas, Sarah L}, Crdt = {2003/03/04 04:00}, Da = {20030704}, Date = {2003 Jul}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20030912}, Dep = {20030115}, Edat = {2003/03/04 04:00}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {2-Amino-5-phosphonovalerate/*pharmacology; Animals; Brain Injuries/physiopathology; Cricetinae; Electrophysiology; Excitatory Amino Acid Antagonists/*pharmacology; Mesocricetus; *Neurons/drug effects/metabolism; Photic Stimulation; Receptors, N-Methyl-D-Aspartate/*antagonists \& inhibitors; Superior Colliculi/*drug effects/*physiopathology/surgery; Visual Fields; Visual Perception}, Mhda = {2003/09/13 05:00}, Month = {Jul}, Number = {1}, Own = {NLM}, Pages = {110--119}, Phst = {2003/01/15 {$[$}aheadofprint{$]$}}, Pii = {01029.2002}, Pl = {United States}, pmid = {12611963}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Excitatory Amino Acid Antagonists); 0 (Receptors, N-Methyl-D-Aspartate); 76726-92-6 (2-Amino-5-phosphonovalerate)}, Sb = {IM}, Status = {MEDLINE}, Title = {NMDA receptor blockade in the superior colliculus increases receptive field size without altering velocity and size tuning}, Volume = {90}, Year = {2003}, url = {papers/Razak_JNeurophysiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01029.2002}} @article{Razak:2006, Abstract = {Neurons in the superficial layers of the midbrain superior colliculus (SC) exhibit distinct tuning properties for visual stimuli, but, unlike neurons in the geniculocortical visual pathway, most respond best to visual stimuli that are smaller than the classical receptive field (RF). The mechanism underlying this size selectivity may depend on the number and pattern of feedforward retinal inputs and/or the balance between inhibition and excitation within the RF. We have previously shown that chronic blockade of NMDA receptors (NMDA-R), which increases the convergence of retinal afferents onto SC neurons, does not alter size selectivity in the SC. This suggests that the number of retinal inputs does not determine size selectivity. Here we show, using single unit extracellular recordings from the SC of normal hamsters, that size selectivity in neurons selective for small stimulus size is correlated with the strength of inhibition within the RF. We also show that dark rearing causes concomitant reductions in both inhibition and size selectivity. In addition, dark rearing increases the percentage of neurons non-selective for stimulus size. Finally, we show that chronic blockade of NMDA-R, a procedure that does not alter size tuning, also does not change the strength of inhibition within the RF. Taken together, these results argue that inhibition within the RF underlies selectivity for small stimulus size and that inhibition must be intact for size tuning to be preserved after developmental manipulations of activity. In addition, these results suggest that regulation of the balance between excitation and inhibition within the RF does not require NMDA-R activity but does depend on visual experience. These results suggest that developmental experience influences neural response properties through an alteration of inhibitory circuitry.}, Address = {Graduate Program in Neurobiology and Behavior, Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA.}, Author = {Razak, Khaleel A and Pallas, Sarah L}, Crdt = {2006/10/06 09:00}, Da = {20061005}, Date = {2006 Sep-Oct}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20061212}, Edat = {2006/10/06 09:00}, Gr = {EY-12696/EY/NEI NIH HHS/United States}, Issn = {0952-5238 (Print)}, Jid = {8809466}, Journal = {Vis Neurosci}, Jt = {Visual neuroscience}, Language = {eng}, Lr = {20071115}, Mh = {2-Amino-5-phosphonovalerate/pharmacology; Action Potentials/drug effects/physiology; Animals; Cricetinae; Dark Adaptation/*physiology; Excitatory Amino Acid Antagonists/pharmacology; Mesocricetus; Neural Inhibition/drug effects/*physiology; Neurons/drug effects/*physiology; Photic Stimulation/methods; Size Perception/*physiology; Superior Colliculi/*cytology; Visual Fields/drug effects/*physiology; Visual Pathways/physiology}, Mhda = {2006/12/13 09:00}, Month = {Sep-Oct}, Number = {5}, Own = {NLM}, Pages = {741--748}, Phst = {2006/03/14 {$[$}received{$]$}; 2006/03/30 {$[$}accepted{$]$}}, Pii = {S0952523806230062}, Pl = {England}, pmid = {17020630}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.}, Rn = {0 (Excitatory Amino Acid Antagonists); 76726-92-6 (2-Amino-5-phosphonovalerate)}, Sb = {IM}, Status = {MEDLINE}, Title = {Dark rearing reveals the mechanism underlying stimulus size tuning of superior colliculus neurons}, Volume = {23}, Year = {2006}, url = {papers/Razak_VisNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1017/S0952523806230062}} @article{Guimera:2006a, Abstract = {The mouse Mgn protein (Helt) is structurally related to the neurogenic Drosophila hairy and Enhancer of split [h/E(spl)] proteins, but its unique structural properties distinguish it from other members of the family. Mgn expression shows a spatiotemporal correlation with GABAergic markers in several brain regions. We report here that homozygous Mgn-null mice die between the second and the fifth postnatal week of age, and show a complete depletion of Gad65 and Gad67 expression in the superior colliculus and a reduction in the inferior colliculus. Other brain regions, as well as other neural systems, are not affected. The progenitor GABAergic cells appear to be generated in right numbers but fail to become GABAergic neurons. The phenotype of the mice is consistent with reduced GABAergic activity. Thus, our in vivo study provides evidence that Mgn is the key regulator of GABAergic neurons, controlling their specification in the dorsal midbrain. Another conclusion from our results is that the function of Mgn shows a previously unrecognized role for h/E(spl)-related transcription factors in the dorsal midbrain GABAergic cell differentiation. Vertebrate h/E(spl)-related genes can no longer be regarded solely as a factors that confer generic neurogenic properties, but as key components for the subtype-neuronal identity in the mammalian CNS.}, Address = {GSF-National Research Center for Environment and Health, Institute of Developmental Genetics, 35/8006, Ingolstadter Landstrasse, 1, Neuherberg, Germany. guimera@gsf.de}, Author = {Guimera, Jordi and Weisenhorn, Daniela Vogt and Wurst, Wolfgang}, Crdt = {2006/09/14 09:00}, Da = {20060913}, Date = {2006 Oct}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20061128}, Edat = {2006/09/14 09:00}, Issn = {0950-1991 (Print)}, Jid = {8701744}, Journal = {Development}, Jt = {Development (Cambridge, England)}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Basic Helix-Loop-Helix Transcription Factors/analysis/genetics/*metabolism; Biological Markers/analysis/metabolism; *Cell Differentiation/genetics; Genes, Lethal; Glutamate Decarboxylase/analysis/*metabolism; Homozygote; Isoenzymes/analysis/*metabolism; Mice; Mice, Mutant Strains; Neurons/chemistry/cytology/metabolism; Phenotype; Repressor Proteins/analysis/genetics/*metabolism; Superior Colliculi/cytology/*growth \& development/metabolism; gamma-Aminobutyric Acid/*metabolism}, Mhda = {2006/12/09 09:00}, Month = {Oct}, Number = {19}, Own = {NLM}, Pages = {3847--3857}, Pii = {133/19/3847}, Pl = {England}, pmid = {16968817}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't}, Rn = {0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Biological Markers); 0 (Helt protein, mouse); 0 (Isoenzymes); 0 (Repressor Proteins); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 1); EC 4.1.1.15 (glutamate decarboxylase 2)}, Sb = {IM}, Status = {MEDLINE}, Title = {Megane/Heslike is required for normal GABAergic differentiation in the mouse superior colliculus}, Volume = {133}, Year = {2006}, url = {papers/Guimera_Development2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.02557}} @article{Carrasco:2005, Abstract = {Sensory deprivation is thought to have an adverse effect on visual development and to prolong the critical period for plasticity. Once the animal reaches adulthood, however, synaptic connectivity is understood to be largely stable. We reported previously that N-methyl-D-aspartate (NMDA) receptor blockade in the superior colliculus of the Syrian hamster prevents refinement of receptive fields (RFs) in normal or compressed retinotopic projections, resulting in target neurons with enlarged RFs but normal stimulus tuning. Here we asked whether visually driven activity is necessary for refinement or maintenance of retinotopic maps or if spontaneous activity is sufficient. Animals were deprived of light either in adulthood only or from birth until the time of recording. We found that dark rearing from birth to 2 mo of age had no effect on the timing and extent of RF refinement as assessed with single unit extracellular recordings. Visual deprivation in adulthood also had no effect. Continuous dark rearing from birth into adulthood, however, resulted in a progressive loss of refinement, resulting in enlarged, asymmetric receptive fields and altered surround suppression in adulthood. Thus unlike in visual cortex, early visually driven activity is not necessary for refinement of receptive fields during development, but is required to maintain refined visual projections in adulthood. Because the map can refine normally in the dark, these results argue against a deprivation-induced delay in critical period closure, and suggest instead that early visual deprivation leaves target neurons more vulnerable to deprivation that continues after refinement.}, Address = {Graduate Program in Neurobiology and Behavior, Department of Biology, Georgia State University, 24 Peachtree Center Ave., Atlanta, Georgia 30303, USA.}, Author = {Carrasco, M M and Razak, K A and Pallas, S L}, Crdt = {2005/05/27 09:00}, Da = {20050817}, Date = {2005 Sep}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20051011}, Dep = {20050525}, Edat = {2005/05/27 09:00}, Gr = {EY-12696/EY/NEI NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Language = {eng}, Lr = {20071115}, Mh = {Action Potentials/physiology; Age Factors; Animals; Animals, Newborn; *Brain Mapping; Cricetinae; Darkness; Electrodes; Neurons/*physiology; Photic Stimulation/methods; Sensory Deprivation/physiology; Superior Colliculi/*cytology/physiology; Visual Fields/*physiology; Visual Pathways/*physiology; Visual Perception/*physiology}, Mhda = {2005/10/12 09:00}, Month = {Sep}, Number = {3}, Own = {NLM}, Pages = {1962--1970}, Phst = {2005/05/25 {$[$}aheadofprint{$]$}}, Pii = {00166.2005}, Pl = {United States}, pmid = {15917326}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Visual experience is necessary for maintenance but not development of receptive fields in superior colliculus}, Volume = {94}, Year = {2005}, url = {papers/Carrasco_JNeurophysiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00166.2005}} @article{Razak:2005, Abstract = {Superior colliculus (SC)-mediated control of visuomotor behavior depends on neuronal selectivity for stimulus velocity. However, the mechanism responsible for velocity tuning in SC neurons is unclear. It was shown in a previous study of anesthetized, decorticate hamsters that the number and distribution of feed-forward retinal inputs are not critical for velocity tuning. Here the alternate hypothesis that inhibition from the surround determines velocity tuning of SC neurons was tested. Surround inhibition was present in 65% (43/66) of SC neurons recorded in the superficial gray layer. Neurons within this group that were selective for slowly moving stimuli exhibited spatially asymmetric surround inhibition, and their velocity tuning arose by preferential suppression of responses to rapidly moving stimuli. In the other 35% (23/66) of SC neurons recorded, surround inhibition was weak or absent and did not play a role in velocity tuning. Most neurons with surround inhibition were nonselective for the duration of stationary flashed stimuli, whereas neurons without surround inhibition were selective for stimulus duration. The majority of neurons that preferred intermediate or rapidly moving stimuli exhibited spatially symmetric surround inhibition. In these neurons, occluding the surround reduced velocity selectivity by enhancing responses to slowly moving stimuli. Based on these data, a model is proposed suggesting spatiotemporal interactions between inhibition and excitation that could underlie velocity tuning.}, Address = {Department of Biology, Georgia State University, 24 Peachtree Center Ave., Atlanta, GA 30303, USA.}, Author = {Razak, Khaleel A and Pallas, Sarah L}, Crdt = {2005/08/05 09:00}, Da = {20051013}, Date = {2005 Nov}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20051202}, Dep = {20050803}, Edat = {2005/08/05 09:00}, Gr = {EY-12696/EY/NEI NIH HHS/United States; R01 EY012696-01A1/EY/NEI NIH HHS/United States; R01 EY012696-02/EY/NEI NIH HHS/United States; R01 EY012696-03/EY/NEI NIH HHS/United States}, Issn = {0022-3077 (Print)}, Jid = {0375404}, Journal = {J Neurophysiol}, Jt = {Journal of neurophysiology}, Language = {eng}, Lr = {20081120}, Mh = {Action Potentials/*physiology; Adaptation, Physiological/physiology; Animals; Cricetinae; Evoked Potentials, Visual/*physiology; Mesocricetus; Motion Perception/*physiology; Nerve Net/*physiology; Neural Inhibition/physiology; Neurons/*physiology; Photic Stimulation/methods; Superior Colliculi/*physiology}, Mhda = {2005/12/13 09:00}, Mid = {NIHMS12318}, Month = {Nov}, Number = {5}, Oid = {NLM: NIHMS12318; NLM: PMC1752200}, Own = {NLM}, Pages = {3573--3589}, Phst = {2005/08/03 {$[$}aheadofprint{$]$}}, Pii = {00816.2004}, Pl = {United States}, Pmc = {PMC1752200}, pmid = {16079191}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.}, Sb = {IM}, Status = {MEDLINE}, Title = {Neural mechanisms of stimulus velocity tuning in the superior colliculus}, Volume = {94}, Year = {2005}, url = {papers/Razak_JNeurophysiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00816.2004}} @article{Pallas:2006, Address = {Department of Biology, Georgia State University, Atlanta, Georgia 30303, USA. spallas@gsu.edu}, Author = {Pallas, Sarah L and Wenner, Peter and Gonzalez-Islas, Carlos and Fagiolini, Michela and Razak, Khaleel A and Kim, Gunsoo and Sanes, Dan and Roerig, Birgit}, Crdt = {2006/10/13 09:00}, Da = {20061012}, Date = {2006 Oct 11}, Date-Added = {2009-03-25 23:16:15 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20061108}, Edat = {2006/10/13 09:00}, Gr = {DC006864/DC/NIDCD NIH HHS/United States; DC05202/DC/NIDCD NIH HHS/United States; DC4199/DC/NIDCD NIH HHS/United States; EY12696/EY/NEI NIH HHS/United States; EY12702/EY/NEI NIH HHS/United States; NS046510/NS/NINDS NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Language = {eng}, Lr = {20071114}, Mh = {Animals; Humans; Nerve Net/*growth \& development; Neural Inhibition/*physiology; Neuronal Plasticity/*physiology; Synaptic Transmission/physiology}, Mhda = {2006/11/10 09:00}, Month = {Oct}, Number = {41}, Own = {NLM}, Pages = {10358--10361}, Pii = {26/41/10358}, Pl = {United States}, pmid = {17035517}, Pst = {ppublish}, Pt = {Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Review}, Rf = {50}, Sb = {IM}, Status = {MEDLINE}, Title = {Developmental plasticity of inhibitory circuitry}, Volume = {26}, Year = {2006}, url = {papers/Pallas_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3516-06.2006}} @article{Wayman:2006, Abstract = {Members of the Wnt signaling family are important mediators of numerous developmental events, including activity-dependent dendrite development, but the pathways regulating expression and secretion of Wnt in response to neuronal activity are poorly defined. Here, we identify an NMDA receptor-mediated, Ca2+-dependent signaling pathway that couples neuronal activity to dendritic arborization through enhanced Wnt synthesis and secretion. Activity-dependent dendritic outgrowth and branching in cultured hippocampal neurons and slices is mediated through activation by CaM-dependent protein kinase kinase (CaMKK) of the membrane-associated gamma isoform of CaMKI. Downstream effectors of CaMKI include the MAP-kinase pathway of Ras/MEK/ERK and the transcription factor CREB. A serial analysis of chromatin occupancy screen identified Wnt-2 as an activity-dependent CREB-responsive gene. Neuronal activity enhances CREB-dependent transcription of Wnt-2, and expression of Wnt-2 stimulates dendritic arborization. This novel signaling pathway contributes to dynamic remodeling of the dendritic architecture in response to neuronal activity during development.}, Address = {Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.}, Author = {Wayman, Gary A and Impey, Soren and Marks, Daniel and Saneyoshi, Takeo and Grant, Wilmon F and Derkach, Victor and Soderling, Thomas R}, Cin = {Neuron. 2006 Jun 15;50(6):813-5. PMID: 16772162}, Crdt = {2006/06/15 09:00}, Da = {20060614}, Date = {2006 Jun 15}, Date-Added = {2009-03-25 23:12:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20060725}, Edat = {2006/06/15 09:00}, Gr = {R01 GM041292/GM/NIGMS NIH HHS/United States}, Issn = {0896-6273 (Print)}, Jid = {8809320}, Journal = {Neuron}, Jt = {Neuron}, Language = {eng}, Lr = {20071115}, Mh = {Animals; Animals, Newborn; Calcium-Calmodulin-Dependent Protein Kinase Type 1; Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism/physiology; Cells, Cultured; Cyclic AMP Response Element-Binding Protein/genetics/*physiology; Dendrites/enzymology/genetics/*physiology; Enzyme Activation/physiology; Hippocampus/cytology/enzymology/metabolism/physiology; Organ Culture Techniques; Rats; Rats, Sprague-Dawley; Transcription, Genetic/*genetics; Wnt2 Protein/genetics/*metabolism}, Mhda = {2006/07/26 09:00}, Month = {Jun}, Number = {6}, Own = {NLM}, Pages = {897--909}, Phst = {2005/10/13 {$[$}received{$]$}; 2006/04/11 {$[$}revised{$]$}; 2006/05/02 {$[$}accepted{$]$}}, Pii = {S0896-6273(06)00374-6}, Pl = {United States}, pmid = {16772171}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, N.I.H., Extramural}, Rn = {0 (Cyclic AMP Response Element-Binding Protein); 0 (Wnt2 Protein); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 1); EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases); EC 2.7.11.17 (Camk1 protein, rat); EC 2.7.11.17 (Pnck protein, rat)}, Sb = {IM}, Status = {MEDLINE}, Title = {Activity-dependent dendritic arborization mediated by CaM-kinase I activation and enhanced CREB-dependent transcription of Wnt-2}, Volume = {50}, Year = {2006}, url = {papers/Wayman_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.05.008}} @article{Chattopadhyaya:2004, Abstract = {The neocortical GABAergic network consists of diverse interneuron cell types that display distinct physiological properties and target their innervations to subcellular compartments of principal neurons. Inhibition directed toward the soma and proximal dendrites is crucial in regulating the output of pyramidal neurons, but the development of perisomatic innervation is poorly understood because of the lack of specific synaptic markers. In the primary visual cortex, for example, it is unknown whether, and to what extent, the formation and maturation of perisomatic synapses are intrinsic to cortical circuits or are regulated by sensory experience. Using bacterial artificial chromosome transgenic mice that label a defined class of perisomatic synapses with green fluorescent protein, here we show that perisomatic innervation developed during a protracted postnatal period after eye opening. Maturation of perisomatic innervation was significantly retarded by visual deprivation during the third, but not the fifth, postnatal week, implicating an important role for sensory input. To examine the role of cortical intrinsic mechanisms, we developed a method to visualize perisomatic synapses from single basket interneurons in cortical organotypic cultures. Characteristic perisomatic synapses formed through a stereotyped process, involving the extension of distinct terminal branches and proliferation of perisomatic boutons. Neuronal spiking in organotypic cultures was necessary for the proliferation of boutons and the extension, but not the maintenance, of terminal branches. Together, our results suggest that although the formation of perisomatic synapses is intrinsic to the cortex, visual experience can influence the maturation and pattern of perisomatic innervation during a postnatal critical period by modulating the level of neural activity within cortical circuits.}, Address = {Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.}, Author = {Chattopadhyaya, Bidisha and Di Cristo, Graziella and Higashiyama, Hiroyuki and Knott, Graham W and Kuhlman, Sandra J and Welker, Egbert and Huang, Z Josh}, Crdt = {2004/10/29 09:00}, Da = {20041028}, Date = {2004 Oct 27}, Date-Added = {2009-03-25 23:12:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20050519}, Edat = {2004/10/29 09:00}, Gr = {R01 EY13564-01/EY/NEI NIH HHS/United States}, Issn = {1529-2401 (Electronic)}, Jid = {8102140}, Journal = {J Neurosci}, Jt = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, Language = {eng}, Lr = {20081121}, Mh = {Action Potentials/physiology; Animals; Chromosomes, Artificial, Bacterial; DNA Repair; Glutamate Decarboxylase/genetics; Green Fluorescent Proteins/genetics; Interneurons/*physiology; Isoenzymes/genetics; Mice; Mice, Transgenic; Neural Inhibition/physiology; Neuronal Plasticity/physiology; Presynaptic Terminals/physiology; Pyramidal Cells/physiology; Recombinant Fusion Proteins; Sensory Deprivation/physiology; Synapses/*physiology; Tetrodotoxin/pharmacology; Time Factors; Tissue Culture Techniques; Vision, Ocular/*physiology; Visual Cortex/*growth \& development/*physiology; gamma-Aminobutyric Acid/*physiology}, Mhda = {2005/05/20 09:00}, Month = {Oct}, Number = {43}, Own = {NLM}, Pages = {9598--9611}, Pii = {24/43/9598}, Pl = {United States}, pmid = {15509747}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Isoenzymes); 0 (Recombinant Fusion Proteins); 147336-22-9 (Green Fluorescent Proteins); 4368-28-9 (Tetrodotoxin); 56-12-2 (gamma-Aminobutyric Acid); EC 4.1.1.15 (Glutamate Decarboxylase); EC 4.1.1.15 (glutamate decarboxylase 1)}, Sb = {IM}, Status = {MEDLINE}, Title = {Experience and activity-dependent maturation of perisomatic GABAergic innervation in primary visual cortex during a postnatal critical period}, Volume = {24}, Year = {2004}, url = {papers/Chattopadhyaya_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1851-04.2004}} @article{Tumbar:2004, Abstract = {Many adult regenerative cells divide infrequently but have high proliferative capacity. We developed a strategy to fluorescently label slow-cycling cells in a cell type-specific fashion. We used this method to purify the label-retaining cells (LRCs) that mark the skin stem cell (SC) niche. We found that these cells rarely divide within their niche but change properties abruptly when stimulated to exit. We determined their transcriptional profile, which, when compared to progeny and other SCs, defines the niche. Many of the >100 messenger RNAs preferentially expressed in the niche encode surface receptors and secreted proteins, enabling LRCs to signal and respond to their environment.}, Address = {Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, NY 10021, USA.}, Author = {Tumbar, Tudorita and Guasch, Geraldine and Greco, Valentina and Blanpain, Cedric and Lowry, William E and Rendl, Michael and Fuchs, Elaine}, Crdt = {2003/12/13 05:00}, Da = {20040116}, Date = {2004 Jan 16}, Date-Added = {2009-03-25 23:08:42 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20040209}, Dep = {20031211}, Edat = {2003/12/13 05:00}, Gr = {R01 AR050452-04/AR/NIAMS NIH HHS/United States}, Issn = {1095-9203 (Electronic)}, Jid = {0404511}, Journal = {Science}, Jt = {Science (New York, N.Y.)}, Language = {eng}, Lr = {20081120}, Mh = {Animals; Cell Cycle; Cell Division; Cell Separation; Epidermis/*cytology/physiology; Epithelial Cells/*cytology/physiology; Gene Expression Profiling; Gene Expression Regulation; Green Fluorescent Proteins; Hair Follicle/*cytology/physiology; Histones/genetics/metabolism; Keratinocytes/cytology; Luminescent Proteins/genetics/metabolism; Mice; Mice, Transgenic; Microscopy, Fluorescence; Multipotent Stem Cells/cytology/*physiology; Oligonucleotide Array Sequence Analysis; RNA, Messenger/genetics/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic}, Mhda = {2004/02/11 05:00}, Mid = {NIHMS44867}, Month = {Jan}, Number = {5656}, Oid = {NLM: NIHMS44867; NLM: PMC2405920}, Own = {NLM}, Pages = {359--363}, Phst = {2003/12/11 {$[$}aheadofprint{$]$}}, Pii = {1092436}, Pl = {United States}, Pmc = {PMC2405920}, pmid = {14671312}, Pst = {ppublish}, Pt = {Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Histones); 0 (Luminescent Proteins); 0 (RNA, Messenger); 147336-22-9 (Green Fluorescent Proteins)}, Sb = {IM}, Status = {MEDLINE}, Title = {Defining the epithelial stem cell niche in skin}, Volume = {303}, Year = {2004}, url = {papers/Tumbar_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1092436}} @article{Alonso:2003, Abstract = {Tissue stem cells form the cellular base for organ homeostasis and repair. Stem cells have the unusual ability to renew themselves over the lifetime of the organ while producing daughter cells that differentiate into one or multiple lineages. Difficult to identify and characterize in any tissue, these cells are nonetheless hotly pursued because they hold the potential promise of therapeutic reprogramming to grow human tissue in vitro, for the treatment of human disease. The mammalian skin epithelium exhibits remarkable turnover, punctuated by periods of even more rapid production after injury due to burn or wounding. The stem cells responsible for supplying this tissue with cellular substrate are not yet easily distinguishable from neighboring cells. However, in recent years a significant body of work has begun to characterize the skin epithelial stem cells, both in tissue culture and in mouse and human skin. Some epithelial cells cultured from skin exhibit prodigious proliferative potential; in fact, for >20 years now, cultured human skin has been used as a source of new skin to engraft onto damaged areas of burn patients, representing one of the first therapeutic uses of stem cells. Cell fate choices, including both self-renewal and differentiation, are crucial biological features of stem cells that are still poorly understood. Skin epithelial stem cells represent a ripe target for research into the fundamental mechanisms underlying these important processes.}, Address = {Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA.}, Author = {Alonso, Laura and Fuchs, Elaine}, Crdt = {2003/08/13 05:00}, Da = {20031001}, Date = {2003 Sep 30}, Date-Added = {2009-03-25 23:03:31 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20031104}, Dep = {20030811}, Edat = {2003/08/13 05:00}, Gr = {R01-AR31737/AR/NIAMS NIH HHS/United States}, Issn = {0027-8424 (Print)}, Jid = {7505876}, Journal = {Proc Natl Acad Sci U S A}, Jt = {Proceedings of the National Academy of Sciences of the United States of America}, Language = {eng}, Lr = {20081120}, Mh = {Animals; Cell Differentiation; Cells, Cultured; Epithelial Cells/cytology; Hair Follicle/cytology; Humans; Keratinocytes/cytology/transplantation; Skin/*cytology; Stem Cells/*cytology/physiology}, Mhda = {2003/11/05 05:00}, Month = {Sep}, Oid = {NLM: PMC304094}, Own = {NLM}, Pages = {11830--11835}, Phst = {2003/08/11 {$[$}aheadofprint{$]$}}, Pii = {1734203100}, Pl = {United States}, Pmc = {PMC304094}, pmid = {12913119}, Pst = {ppublish}, Pt = {Journal Article; Research Support, U.S. Gov't, P.H.S.; Review}, Rf = {64}, Sb = {IM}, Status = {MEDLINE}, Title = {Stem cells of the skin epithelium}, Volume = {100 Suppl 1}, Year = {2003}, url = {papers/Alonso_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1734203100}} @article{Tagawa:2005, Abstract = {The precise period when experience shapes neural circuits in the mouse visual system is unknown. We used Arc induction to monitor the functional pattern of ipsilateral eye representation in cortex during normal development and after visual deprivation. After monocular deprivation during the critical period, Arc induction reflects ocular dominance (OD) shifts within the binocular zone. Arc induction also reports faithfully expected OD shifts in cat. Shifts towards the open eye and weakening of the deprived eye were seen in layer 4 after the critical period ends and also before it begins. These shifts include an unexpected spatial expansion of Arc induction into the monocular zone. However, this plasticity is not present in adult layer 6. Thus, functionally assessed OD can be altered in cortex by ocular imbalances substantially earlier and far later than expected.}, Address = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.}, Author = {Tagawa, Yoshiaki and Kanold, Patrick O and Majdan, Marta and Shatz, Carla J}, Crdt = {2005/02/22 09:00}, Da = {20050304}, Date = {2005 Mar}, Date-Added = {2009-03-25 22:56:58 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Dcom = {20050509}, Dep = {20050220}, Edat = {2005/02/22 09:00}, Gr = {F32 EY1352/EY/NEI NIH HHS/United States; R01 EY02858/EY/NEI NIH HHS/United States}, Issn = {1097-6256 (Print)}, Jid = {9809671}, Journal = {Nat Neurosci}, Jt = {Nature neuroscience}, Language = {eng}, Lr = {20081121}, Mh = {Age Factors; Anesthetics, Local/pharmacology; Animals; Animals, Newborn; Brain Mapping; *Critical Period (Psychology); Cytoskeletal Proteins/genetics/metabolism; Densitometry/methods; Dominance, Ocular/*physiology; Enzyme Induction/physiology/radiation effects; Eye Enucleation/methods; Gene Expression Regulation/physiology/radiation effects; In Situ Hybridization/methods; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins/genetics/metabolism; Neuronal Plasticity/*physiology; Photic Stimulation; Proline/metabolism; Proto-Oncogene Proteins c-fos/genetics/metabolism; RNA, Messenger/metabolism; Statistics, Nonparametric; Tetrodotoxin/pharmacology; Tritium/metabolism; Vision, Ocular/*physiology; Visual Cortex/growth \& development/*physiology; Visual Pathways/anatomy \& histology/growth \& development/*physiology}, Mhda = {2005/05/10 09:00}, Month = {Mar}, Number = {3}, Own = {NLM}, Pages = {380--388}, Phst = {2004/12/14 {$[$}received{$]$}; 2005/01/27 {$[$}accepted{$]$}; 2005/02/20 {$[$}aheadofprint{$]$}}, Pii = {nn1410}, Pl = {United States}, pmid = {15723060}, Pst = {ppublish}, Pt = {Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.}, Rn = {0 (Anesthetics, Local); 0 (Cytoskeletal Proteins); 0 (Nerve Tissue Proteins); 0 (Proto-Oncogene Proteins c-fos); 0 (RNA, Messenger); 0 (activity regulated cytoskeletal-associated protein); 10028-17-8 (Tritium); 147-85-3 (Proline); 4368-28-9 (Tetrodotoxin)}, Sb = {IM}, Status = {MEDLINE}, Title = {Multiple periods of functional ocular dominance plasticity in mouse visual cortex}, Volume = {8}, Year = {2005}, url = {papers/Tagawa_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1410}} @article{Aaronson:1971, Author = {Aaronson, S. A. and Todaro, G. J. and Scolnick, E. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {15 ERVs retroelements;Embryo;Clone Cells;RNA Viruses;Enzyme Induction;24 Pubmed search results 2008;Cell Line;15 Retrovirus mechanism;Mice;Bromodeoxyuridine;DNA Nucleotidyltransferases;Cells, Cultured;Animals}, Medline = {72042139}, Month = {10}, Nlm_Id = {0404511}, Number = {5}, Pages = {157-9}, Pubmed = {5119627}, Title = {Induction of murine C-type viruses from clonal lines of virus-free BALB-3T3 cells}, Uuid = {6E4A3F07-22B3-41A2-9CF0-E6CE79B42132}, Volume = {174}, Year = {1971}} @article{Abbott:2004, Author = {Abbott, Alison}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Cerebrovascular Accident;21 Neurodegenerative;21 Neurophysiology;Nerve Regeneration;Human;Stem Cells;Cell Division;Tissue Therapy;Male;Brain;Neurons;news}, Month = {5}, Nlm_Id = {0410462}, Number = {6990}, Pages = {338-9}, Pii = {429338a}, Pubmed = {15164032}, Title = {Striking back}, Uuid = {7236B95F-747D-43F4-B5E1-8479D47AE6FE}, Volume = {429}, Year = {2004}, url = {papers/Abbott_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/429338a}} @article{Abdel-Aziz:2000, Abstract = {PURPOSE: An intact and fully functional multiprotein DNA replication complex (DNA synthesome) from human as well as from murine mammary carcinoma cells was first isolated and characterized in our laboratory. The human cell synthesome supports the in vitro origin-specific simian virus 40 (SV40) DNA replication reaction in the presence of the viral large T-antigen using a semiconservative mechanism and has been shown to contain all the proteins and enzymes required to support DNA synthesis. We are currently using the DNA synthesome as a unique model for analyzing the mechanism of action of anticancer drugs affecting DNA replication. The purpose of this study was to further investigate the mechanism of action of ara-C using the DNA synthesome isolated from the human breast cancer cell line MDA MB-468. METHODS: Synthesome-mediated SV40 DNA replication was performed in the presence of various concentrations of ara-CTP (the active metabolite of ara-C) and the types of daughter DNA molecules produced were analyzed lusing neutral and alkaline gel electrophoresis. We also examined the effect of ara-C on intact MDA MB-468 cell DNA synthesis and on cell proliferation. In addition, we studied the effect of ara-CTP on the activity of some of the synthesome target proteins (the DNA polymerases alpha and delta). RESULTS: Full-length daughter DNA molecules were obtained in the presence of low concentrations of ara-CTP while at higher concentrations, there was an inhibition of full-length daughter DNA synthesis. The findings suggest that specifically the initiation phase of DNA synthesis was inhibited by ara-CTP since the production of the short Okazaki fragments was suppressed at all concentrations of the drug above 10 microM. In addition, it was found that the IC50 of ara-CTP for inhibition of synthesome-mediated in vitro DNA replication was comparable to that required to inhibit intact cell DNA synthesis. Further experimentation has shown that ara-CTP preferentially inhibits the activity of the synthesome-associated DNA polymerase alpha enzyme while the DNA polymerase delta seems to be resistant to the inhibitory effect of that drug. CONCLUSIONS: Our results indicate that ara-C's action on DNA replication is mediated primarily through DNA polymerase alpha and suggest that this enzyme plays a key role in DNA synthetic initiation events. The results also provide definitive support for the use of the DNA synthesome as a unique and powerful model for analyzing the mechanism of action of anticancer drugs which directly affect DNA replication. 0344-5704 Journal Article}, Author = {Abdel-Aziz, W. and Jiang, H. Y. and Hickey, R. J. and Malkas, L. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Journal = {Cancer Chemother Pharmacol}, Keywords = {EE pdf;Tumor Cells, Cultured;Cell Division/drug effects;DNA Replication/*drug effects;Antimetabolites, Antineoplastic/*pharmacology;DNA Polymerase III/biosynthesis;DNA, Neoplasm/*biosynthesis;Human;08 Aberrant cell cycle;Breast Neoplasms/metabolism;Cytarabine/*pharmacology;Antigens, Polyomavirus Transforming/metabolism;Replicon/drug effects;Support, U.S. Gov't, P.H.S.;DNA Polymerase I/biosynthesis;Arabinofuranosylcytosine Triphosphate/pharmacology}, Number = {4}, Organization = {University of Maryland School of Medicine, Department of Pharmacology and Experimental Therapeutics, Baltimore, MD 21201, USA.}, Pages = {312-9}, Title = {Ara-C affects formation of cancer cell DNA synthesome replication intermediates}, Uuid = {5ABDDBB5-1C18-4F45-AF57-A7FF63707641}, Volume = {45}, Year = {2000}, url = {papers/Abdel-Aziz_CancerChemotherPharmacol2000.pdf}} @article{Abe:2003, Abstract = {BACKGROUND: BM cells have been shown to give rise to progeny of various cell lineages, including cells in lung and liver. This investigation evaluated whether purified BM mononuclear cells and side population (SP) cells that have hematopoietic stem-cell activity also had this property; whether a TBI preparative regimen was necessary for engraftment; and where BM-derived cells were engrafted. METHODS: Either 1-3 million BM mononuclear cells or 2000 BM SP cells from transgenic enhanced green fluorescent protein-expressing (EGFP) mice were transplanted i.v. to unirradiated or 7-9.5 Gy irradiated recipients. RESULTS: Flow cytometric analysis showed that lung cells (mean 45\%, range 4-70\%) and liver cells (mean 4\%, range 0.4-8.3\%) from irradiated, but not unirradiated recipients, were EGFP donor-derived. Similar results were obtained transplanting BM mononuclear cells or SP cells. Morphologically, donor-derived cells in the lung were primarily monocytes and macrophages. Additionally, lung fibroblasts and Type I, but not Type II, alveolar cells and rare cells in the bronchial epithelium were donor BM derived. In the liver, Kupffer cells, inflammatory cells and small clusters of hepatocytes, but not bile duct cells, were donor-derived. DISCUSSION: BM mononuclear and SP cells generated progeny in some compartments of the lung and liver, but only in TBI recipients. Stem cells in BM can contribute to repair of tissue injury in some compartments, but not to the same extent in the lung and liver.}, Author = {Abe, S. and Lauby, G. and Boyer, C. and Rennard, S. I. and Sharp, J. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {1465-3249}, Journal = {Cytotherapy}, Keywords = {Research Support, Non-U.S. Gov't;Gamma Rays;Animals;Blood Cells;Whole-Body Irradiation;Bone Marrow Transplantation;Serum Albumin;Female;Cell Count;Mice, Transgenic;Liver;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Keratin;Immune Tolerance;Bone Marrow Cells;Survival Rate;Flow Cytometry;Mice;Immunohistochemistry;Graft Survival;Luminescent Proteins;Spleen;Lung}, Nlm_Id = {100895309}, Number = {6}, Organization = {Department of Internal Medicine Pulmonary Section, University of Nebraska Medical Center, Omaha, NE 986395, USA.}, Pages = {523-33}, Pii = {0RJXN5LLRQL82P13}, Pubmed = {14660048}, Title = {Transplanted BM and BM side population cells contribute progeny to the lung and liver in irradiated mice}, Uuid = {54F89858-5CAB-4886-91C0-D937E0BA898E}, Volume = {5}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/14653240310003576}} @article{Abe:1998, Abstract = {In the absence of envelope gene expression, retrovirus packaging cell lines expressing Moloney murine leukemia virus (MLV) gag and pol genes produce large amounts of noninfectious virus-like particles that contain reverse transcriptase, processed Gag protein, and viral RNA (gag-pol RNA particles). We demonstrate that these particles can be made infectious in an in vitro, cell-free system by the addition of a surrogate envelope protein, the G spike glycoprotein of vesicular stomatitis virus (VSV-G). The appearance of infectivity is accompanied by physical association of the G protein with the immature, noninfectious virus particles. Similarly, exposure in vitro of wild-type VSV-G to a fusion-defective pseudotyped virus containing a mutant VSV-G markedly increases the infectivity of the virus to titers similar to those of conventional VSV-G pseudotyped viruses. Furthermore, similar treatment of an amphotropic murine leukemia virus significantly allows infection of BHK cells not otherwise susceptible to infection with native amphotropic virus. The partially cell-free virus maturation system reported here should be useful for studies aimed at the preparation of tissue-targeted retrovirus vectors and will also aid in studies of nucleocapsid-envelope interactions during budding and of virus assembly and virus-receptor interactions during virus uptake into infected cells. It may also represent a potentially useful step toward the eventual development of a completely cell-free retrovirus assembly system.}, Author = {Abe, A. and Chen, S. T. and Miyanohara, A. and Friedmann, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {RNA, Viral;Animals;Humans;Vesicular stomatitis-Indiana virus;Cell Line, Transformed;15 Retrovirus mechanism;Virion;Hela Cells;Viral Envelope Proteins;Cell Line;Research Support, U.S. Gov't, P.H.S.;Moloney murine leukemia virus;Membrane Glycoproteins;Fusion Proteins, gag-pol;Cell-Free System;Cricetinae;24 Pubmed search results 2008;Culture Media;15 PS VSVG receptor;Research Support, Non-U.S. Gov't}, Medline = {98325147}, Month = {8}, Nlm_Id = {0113724}, Number = {8}, Organization = {Department of Pediatrics, Center for Molecular Genetics, University of California, San Diego, La Jolla, California 92093-0634, USA.}, Pages = {6356-61}, Pubmed = {9658075}, Title = {In vitro cell-free conversion of noninfectious Moloney retrovirus particles to an infectious form by the addition of the vesicular stomatitis virus surrogate envelope G protein}, Uuid = {6BA86AC4-4324-11DB-A5D2-000D9346EC2A}, Volume = {72}, Year = {1998}, url = {papers/Abe_JVirol1998.pdf}} @article{Abedi:2004, Abstract = {OBJECTIVE: Murine marrow cells are capable of repopulating skeletal muscle fibers. A point of concern has been the "robustness" of such conversions. We have investigated the impact of type of cell delivery, muscle injury, nature of delivered cell, and stem cell mobilizations on marrow-to-muscle conversion. METHODS: We transplanted green fluorescence protein (GFP)-transgenic marrow into irradiated C57BL/6 mice and then injured anterior tibialis muscle by cardiotoxin. One month after injury, sections were analyzed by standard and deconvolutional microscopy for expression of muscle and hematopoietic markers. RESULTS: Irradiation was essential to conversion, although whether by injury or induction of chimerism is not clear. Cardiotoxin- and, to a lesser extent, PBS-injected muscles showed significant number of GFP(+) muscle fibers, while uninjected muscles showed only rare GFP(+) cells. Marrow conversion to muscle was increased by two cycles of G-CSF mobilization and to a lesser extent by G-CSF and steel or GM-CSF. Transplantation of female GFP to male C57BL/6 and GFP to ROSA26 mice showed fusion of donor cells to recipient muscle. High numbers of donor-derived muscle colonies and up to 12\%GFP(+) muscle cells were seen after mobilization or direct injection. These levels of donor muscle chimerism approach levels that could be clinically significant in developing strategies for the treatment of muscular dystrophies. CONCLUSION: In summary, the conversion of marrow to skeletal muscle cells is based on cell fusion and is critically dependent on injury. This conversion is also numerically significant and increases with mobilization.}, Author = {Abedi, Mehrdad and Greer, Deborah A. and Colvin, Gerald A. and Demers, Delia A. and Dooner, Mark S. and Harpel, Jasha A. and Weier, Heinz-Ulrich U. and Lambert, Jean-Francois F. and Quesenberry, P. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {0301-472X}, Journal = {Exp Hematol}, Keywords = {Hematopoietic Stem Cell Mobilization;Animals;Bone Marrow Transplantation;Muscle Cells;Female;Cell Fusion;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Male;Transplantation Chimera;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Muscle, Skeletal;Mice;Muscle Fibers;Luminescent Proteins;Colony-Stimulating Factors;Regeneration}, Month = {5}, Nlm_Id = {0402313}, Number = {5}, Organization = {Roger Williams Medical Center, Department of Research, Providence, RI 02864, USA. mabedi\@rwmc.org}, Pages = {426-34}, Pii = {S0301472X04000645}, Pubmed = {15145210}, Title = {Robust conversion of marrow cells to skeletal muscle with formation of marrow-derived muscle cell colonies: a multifactorial process}, Uuid = {07AF3ACE-D12E-4AAD-90CE-357A8D1F16E7}, Volume = {32}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.exphem.2004.02.007}} @book{Abeles:1991, Abstract = {90002035 M. Abeles. ill. ; 24 cm. Includes index.}, Author = {Abeles, Moshe}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Isbn = {0521374766}, Keywords = {Neural Transmission.;Cerebral Cortex physiology.;Neural networks (Computer science);Cerebral Cortex anatomy &histology.;M QP363.3 .A24 1991 612.8/25;Neural circuitry.;Cerebral cortex Computer simulation.}, Publisher = {Cambridge University Press}, Title = {Corticonics : neural circuits of the cerebral cortex}, Uuid = {9B4FB550-A5C0-4BD6-9F3C-8E16237C6164}, Year = {1991}} @article{Aberg:2000, Abstract = {In several species, including humans, the dentate granule cell layer (GCL) of the hippocampus exhibits neurogenesis throughout adult life. The ability to regulate adult neurogenesis pharmacologically may be of therapeutic value as a mechanism for replacing lost neurons. Insulin- like growth factor-I (IGF-I) is a growth-promoting peptide hormone that has been shown to have neurotrophic properties. The relationship between IGF-I and adult hippocampal neurogenesis is to date unknown. The aim of this study was to investigate the effect of the peripheral administration of IGF-I on cellular proliferation in the dentate subgranular proliferative zone, which contains neuronal progenitor cells, and on the subsequent migration and differentiation of progenitor cells within the GCL. Using bromodeoxyuridine (BrdU) labeling, we found a significant increase of BrdU-immunoreactive progenitors in the GCL after 6 d of peripheral IGF-I administration. To determine the cell fate in progenitor progeny, we characterized the colocalization of BrdU-immunolabeled cells with cell-specific markers. In animals treated with IGF-I for 20 d, BrdU-positive cells increased significantly. Furthermore, the fraction of newly generated neurons in the GCL increased, as evaluated by the neuronal markers Calbindin D(28K), microtubule-associated protein-2, and NeuN. There was no difference in the fraction of newly generated astrocytes. Thus, our results show that peripheral infusion of IGF-I increases progenitor cell proliferation and selectively induces neurogenesis in the progeny of adult neural progenitor cells. This corresponds to a 78 +/- 17\%(p <0.001) increase in the number of new neurons in IGF-I-treated animals compared with controls.}, Author = {Aberg, M. A. and Aberg, N. D. and Hedbacker, H. and Oscarsson, J. and Eriksson, P. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Neurosci}, Keywords = {Hippocampus/cytology/*drug effects/metabolism;Rats;Female;Bromodeoxyuridine/metabolism;Dentate Gyrus/cytology/drug effects;Animal;Stem Cells/*drug effects/metabolism;Insulin-Like Growth Factor I/*pharmacology;04 Adult neurogenesis factors;Hypophysectomy;Support, Non-U.S. Gov't;Male;C-13}, Number = {8}, Organization = {Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Goteborg University, Goteborg, Sweden.}, Pages = {2896-903.}, Title = {Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus}, Uuid = {52A63FBA-C95F-4154-B7BB-38DA461BA72A}, Volume = {20}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10751442%20http://www.jneurosci.org/cgi/content/full/20/8/2896%20http://www.jneurosci.org/cgi/content/abstract/20/8/2896}} @article{Aboody:2000, Abstract = {One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and migrate widely into normal brain, usually rendering them "elusive"to effective resection, irradiation, chemotherapy, or gene therapy. We demonstrate that neural stem cells (NSCs), when implanted into experimental intracranial gliomas in vivo in adult rodents, distribute themselves quickly and extensively throughout the tumor bed and migrate uniquely in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to stably express a foreign gene. The NSCs "surround"the invading tumor border while "chasing down"infiltrating tumor cells. When implanted intracranially at distant sites from the tumor (e.g., into normal tissue, into the contralateral hemisphere, or into the cerebral ventricles), the donor cells migrate through normal tissue targeting the tumor cells (including human glioblastomas). When implanted outside the CNS intravascularly, NSCs will target an intracranial tumor. NSCs can deliver a therapeutically relevant molecule-cytosine deaminase-such that quantifiable reduction in tumor burden results. These data suggest the adjunctive use of inherently migratory NSCs as a delivery vehicle for targeting therapeutic genes and vectors to refractory, migratory, invasive brain tumors. More broadly, they suggest that NSC migration can be extensive, even in the adult brain and along nonstereotypical routes, if pathology (as modeled here by tumor) is present. 0027-8424 Journal Article}, Author = {Aboody, K. S. and Brown, A. and Rainov, N. G. and Bower, K. A. and Liu, S. and Yang, W. and Small, J. E. and Herrlinger, U. and Ourednik, V. and Black, P. M. and Breakefield, X. O. and Snyder, E. Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {G;Human;Animals;Stem Cells/cytology/*physiology;Nucleoside Deaminases/*genetics;Rats;Brain/*pathology;Neurons/cytology/*physiology;Gene Therapy/methods;Female;11 Glia;Disease Models, Animal;Glioblastoma/*pathology/therapy;Hematopoietic Stem Cell Transplantation;Mice, Nude;Tropism;Rats, Inbred F344;Support, Non-U.S. Gov't;Brain Neoplasms/*pathology/therapy;Cytosine Deaminase;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Mice}, Number = {23}, Organization = {Departments of Neurology, Pediatrics, and Neurosurgery, Children's Hospital, Boston, MA, USA.}, Pages = {12846-51}, Pubmed = {11070094}, Title = {Neural stem cells display extensive tropism for pathology in adult brain: evidence from intracranial gliomas}, Uuid = {62D215A2-5535-4A50-92C3-B7564C9732F0}, Volume = {97}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11070094}} @article{Abraham:2004, Abstract = {In the fetal human hippocampus, Cajal-Retzius (CR) cells coexpress p73, a p53-family member involved in cell survival and apoptosis, and the glycoprotein reelin, crucial for radial migration. We distinguish two populations of putative CR cells. (1). p73/reelin expressing cells appear around 10 gestational weeks (GW) at the cortico-choroid border in the temporal horn of the lateral ventricle (the ventral cortical hem) and occupy the marginal zone (MZ) overlying the ammonic and dentate primordia. (2). Additional p73-positive cells appear from 14 GW onward in the neuroepithelium near the dentate-fimbrial boundary and spread toward the pial surface, flanking the migrating secondary dentate matrix. From 13 to 17 GW, large parts of the dentate gyrus are almost devoid of CR cells. p73/Reelin-positive CR cells appear in the MZ of the suprapyramidal blade at 16 GW and around 21 GW in the infrapyramidal blade. The p73-positive cells of the dentate-fimbrial boundary express reelin when they are close to the pial surface, suggesting that they differentiate into CR cells of the infrapyramidal blade. Reelin-positive, p73-negative interneurons are prominent in the prospective strata lacunosum-moleculare and radiatum of cornu ammonis as early as 14 GW; in the dentate molecular layer and hilus they appear around midgestation. We propose that CR cells of the human hippocampal formation belong to two distinct cell populations: an early one derived from the ventral cortical hem and mainly related to migration of the ammonic and dentate plates and a later appearing one derived from the dentate-fimbrial neuroepithelium, which may be related to the protracted neurogenesis and migration of dentate granule cells, particularly of the infrapyramidal blade.}, Author = {Abraham, Hajnalka and P{\'e}rez-Garc{\'\i}a, Carlos Gustavo and Meyer, Gundela}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {10 Development;10 Hippocampus;Tissue Distribution;DNA-Binding Proteins;Humans;Cells, Cultured;Neocortex;Hippocampus;Serine Endopeptidases;Cell Adhesion Molecules, Neuronal;Cerebellar Nuclei;Genes, Tumor Suppressor;Extracellular Matrix Proteins;Neurons;Nuclear Proteins;Cell Division;Gestational Age;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Month = {5}, Nlm_Id = {9110718}, Number = {5}, Organization = {Department of Anatomy, Faculty of Medicine, University La Laguna, Tenerife, Spain.}, Pages = {484-95}, Pii = {bhh010}, Pubmed = {15054064}, Title = {p73 and Reelin in Cajal-Retzius cells of the developing human hippocampal formation}, Uuid = {CFFD61AC-FCC4-4363-8966-4C2FE1B31F51}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh010}} @article{Adelsberger:2005, Abstract = {Using a new optical fiber-based approach, we demonstrate the presence of recurrent Ca(2+) transients in cortical neurons of non-anesthetized newborn mice in vivo. These Ca(2+) waves reflect the correlated activity of thousands of cells and were detected only in resting, but not in moving pups. Our results suggest that Ca(2+)-dependent cortical maturation occurs predominantly during the intermittent sleep-like resting periods that are characteristic for the first days of postnatal life.}, Author = {Adelsberger, Helmuth and Garaschuk, Olga and Konnerth, Arthur}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Fluorescent Dyes;Animals;Aniline Compounds;Fluoresceins;Calcium;Fiber Optics;21 Calcium imaging;research support, non-u.s. gov't ;Animals, Newborn;Cerebral Cortex;21 Neurophysiology;Rest;Neurons;Photons;Mice;24 Pubmed search results 2008;21 Cortical oscillations;Oscillometry;Research Support, Non-U.S. Gov't}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Physiologisches Institut, Ludwig-Maximilians Universit{\"a}t M{\"u}nchen, Pettenkoferstr. 12, 80336 M{\"u}nchen, Germany.}, Pages = {988-90}, Pii = {nn1502}, Pubmed = {16007081}, Title = {Cortical calcium waves in resting newborn mice}, Uuid = {7199FDC7-D93B-41F3-AEDB-1C78450B2D89}, Volume = {8}, Year = {2005}, url = {papers/Adelsberger_NatNeurosci2005.pdf}, Bdsk-File-2 = {papers/Adelsberger_NatNeurosci2005a.pdf}, Bdsk-File-3 = {papers/Adelsberger_NatNeurosci2005b.pdf}, Bdsk-File-4 = {papers/Adelsberger_NatNeurosci2005c.pdf}, Bdsk-File-5 = {papers/Adelsberger_NatNeurosci2005d.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1502}} @article{Adkins-Muir:2003, Abstract = {This study assessed the behavioral and dendritic structural effects of combining subdural motor cortical electrical stimulation with motor skills training following unilateral sensorimotor cortex lesions in adult male rats. Rats were pre-operatively trained on a skilled forelimb reaching task, the Montoya staircase test, and then received endothelin-1 induced ischemic lesions of the sensorimotor cortex. Ten to 14 days later, electrodes were implanted over the peri-lesion cortical surface. Rats subsequently began 10 days of rehabilitative training on the reaching task in 1 of 3 conditions: 1. 50 Hz stimulation during training, 2. 250 Hz stimulation during training or 3. no stimulation. No significant difference in performance was found between the 250 Hz and no stimulation groups. The 50 Hz stimulation group had significantly greater rates of improvement with the impaired forelimb in comparison to 250 Hz and no stimulation groups combined. Fifty Hz stimulated animals also had a significant increase in the surface density of dendritic processes immunoreactive for the cytoskeletal protein, microtubule-associated protein 2, in the peri-lesion cortex compared to the other groups. These results support the efficacy of combining rehabilitative training with cortical electrical stimulation to improve functional outcome and cortical neuronal structural plasticity following sensorimotor cortical damage.}, Author = {Adkins-Muir, DeAnna L. and Jones, Theresa A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0161-6412}, Journal = {Neurol Res}, Keywords = {Disease Models, Animal;24 Pubmed search results 2008;Corpus Striatum;Recovery of Function;Male;Motor Skills;Brain Ischemia;Cerebral Cortex;Immunohistochemistry;Animals;Sensory Thresholds;Rats, Long-Evans;Forelimb;Dose-Response Relationship, Radiation;Cell Count;Electric Stimulation;Analysis of Variance;Behavior, Animal;Microtubule-Associated Proteins;Dendrites;21 Epilepsy;Neuronal Plasticity;Comparative Study;Electrodes;Body Weight;Endothelin-1;Rats;Staining and Labeling;21 Neurophysiology;Research Support, Non-U.S. Gov't}, Medline = {23031747}, Month = {12}, Nlm_Id = {7905298}, Number = {8}, Organization = {Psychology Department and Neuroscience Institute, University of Texas at Austin, 1 University Station A8000, Austin, TX 78712, USA.}, Pages = {780-8}, Pubmed = {14669519}, Title = {Cortical electrical stimulation combined with rehabilitative training: enhanced functional recovery and dendritic plasticity following focal cortical ischemia in rats}, Uuid = {36683C8D-BBF0-44B1-A4E1-1769C11AB666}, Volume = {25}, Year = {2003}} @article{Aggoun-Aouaoui:1996, Abstract = {In kittens ranging in age between postnatal day (P) 5 and P150, callosal axons originating near the 17/18 border were anterogradely labelled with biocytin and reconstructed from serial sections. At the end of the first postnatal week most of the axons begin to invade the cortex near the 17/18 border with multiple branches; some axons already span the grey matter up to layer 1. Branches tend to grow into the grey matter in loose bundles 3.0.CO;2-M}, Pubmed = {10491570}, Title = {Glial responses to synaptic damage and plasticity}, Uuid = {8CED6A53-EE26-11DA-8605-000D9346EC2A}, Volume = {58}, Year = {1999}} @article{Aldskogius:2001, Abstract = {Microglia has the potential to produce and release a range of factors that directly and/or indirectly promote regeneration in the injured nervous system. The overwhelming evidence indicates, however, that this potential is generally not expressed in vivo. Activated microglia may enhance neuronal degeneration following axotomy, thereby counteracting functional recovery. Microglia does not seem to contribute significantly to axonal outgrowth after peripheral nerve injury, since this process proceeds uneventful even if perineuronal microglia is eliminated. The phagocytic phenotype of microglia is highly suppressed during Wallerian degeneration in the central nervous system. Therefore, microglia is incapable of rapid and efficient removal of myelin debris and its putative growth inhibitory components. In this way, microglia may contribute to regeneration failure in the central nervous system. Structural and temporal correlations are compatible with participation by perineuronal microglia in axotomy-induced shedding of presynaptic terminals, but direct evidence for such participation is lacking. Currently, the most promising case for a promoting effect on neural repair by activated microglia appears to be as a mediator of collateral sprouting, at least in certain brain areas. However, final proof for a critical role of microglia in these instances is still lacking. Results from in vitro studies demonstrate that microglia can develop a regeneration supportive phenotype. Altering the microglial involvement following neural injury from a typically passive or even counterproductive state and into a condition where these cells are actively supporting regeneration and plasticity is, therefore, an exciting challenge and probably a realistic goal.}, Author = {Aldskogius, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {1059-910X}, Journal = {Microsc Res Tech}, Keywords = {Central Nervous System;Nerve Degeneration;Nerve Regeneration;Human;Neuronal Plasticity;Not relevant;11 Glia;Microglia;review, tutorial;Support, Non-U.S. Gov't;Phagocytosis;review}, Medline = {21417960}, Month = {7}, Nlm_Id = {9203012}, Number = {1}, Organization = {Department of Neuroscience, Biomedical Center, Uppsala, Sweden. Hakan.Aldskogius\@neuro.uu.se}, Pages = {40-6}, Pii = {10.1002/jemt.1119}, Pubmed = {11526956}, Title = {Microglia in neuroregeneration}, Uuid = {98BE2D07-FB09-4697-8D1E-FB07B84B5EEE}, Volume = {54}, Year = {2001}} @article{Aldskogius:1998, Abstract = {Axon injury rapidly activates microglial and astroglial cells close to the axotomized neurons. Following motor axon injury, astrocytes upregulate within hour(s) the gap junction protein connexin-43, and within one day glial fibrillary acidic protein (GFAP). Concomitantly, microglial cells proliferate and migrate towards the axotomized neuron perikarya. Analogous responses occur in central termination territories of peripherally injured sensory ganglion cells. The activated microglia express a number of inflammatory and immune mediators. When neuron degeneration occurs, microglia act as phagocytes. This is uncommon after peripheral nerve injury in the adult mammal, however, and the functional implications of the glial cell responses in this situation are unclear. When central axons are injured, the glial cell responses around the affected neuron perikarya appears to be minimal or absent, unless neuron degeneration occurs. Microglia proliferate, and astrocytes upregulate GFAP along central axons undergoing anterograde, Wallerian, degeneration. Although microglia develop into phagocytes, they eliminate the disintegrating myelin very slowly, presumably because they fail to release molecules which facilitate phagocytosis. During later stages of Wallerian degeneration, oligodendrocytes express clusterin, a glycoprotein implicated in several conditions of cell degeneration. A hypothetical scheme for glial cell activation following axon injury is discussed, implying the injured neurons initially interact with adjacent astrocytes. Subsequently, neighbouring resting microglia are activated. These glial reactions are amplified by paracrine and autocrine mechanisms, in which cytokines appear to be important mediators. The specific functional properties of the activated glial cells will determine their influence on neuronal survival, axon regeneration, and synaptic plasticity. The control of the induction and progression of these responses are therefore likely to be critical for the outcome of, for example, neurotrauma, brain ischemia and chronic neurodegenerative diseases.}, Author = {Aldskogius, H. and Kozlova, E. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {Neurons;Neuroglia;Central Nervous System;Cell Communication;Human;11 Glia;review, tutorial;Axotomy;Support, Non-U.S. Gov't;Animals;review;Axons}, Medline = {98265208}, Month = {5}, Nlm_Id = {0370121}, Number = {1}, Organization = {Department of Neuroscience, Biomedical Center, Uppsala, Sweden. Hakan.Aldskogius\@anatomi.uu.se}, Pages = {1-26}, Pii = {S0301008297000932}, Pubmed = {9602498}, Title = {Central neuron-glial and glial-glial interactions following axon injury}, Uuid = {70E11CE7-63ED-4BFC-BBF9-404F5CEC9791}, Volume = {55}, Year = {1998}} @article{Alefeld:1998, Abstract = {Multiple extracellular recording electrodes were used to study the intra- and interhemispheric spread of stimulus-evoked epileptiform responses in adult mouse neocortical slices. Bath application of 20 microM bicuculline methiodide induced epileptiform activity that propagated at approximately 0.08 m/s over several millimeters in rostro-caudal and medio-lateral direction within the ipsilateral hemisphere and across the corpus callosum to the contralateral hemisphere. A vertical incision from layer II to subcortical regions did not prevent the spread to remote cortical regions, indicating that layer I plays a major role in the lateral propagation of epileptiform activity. The intra- and interhemispheric spread was not influenced by application of an N-methyl-d-aspartate (NMDA) receptor antagonist, but blocked by an antagonist acting at the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)-type glutamate receptor. The potential role of potassium channel activation in controlling the generation or spread of epileptiform activity was tested by applying the potassium channel opener cromakalim and the serotonin type 1A (5-HT1A) receptor agonist (+/-)-8-hydroxydipropylaminotetralin (8-OH-DPAT) to the disinhibited slices. Whereas cromakalim reduced the neuronal excitability and blocked all epileptiform responses, 8-OH-DAPT did not affect the activity pattern. Our results suggest that propagating epileptiform activity in disinhibited neocortical structures is predominantly mediated by activation of AMPA receptors and controllable by activation of a voltage-dependent potassium current.}, Author = {Alefeld, M. and Sutor, B. and Luhmann, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Epilepsy;Electric Stimulation;Mice;Research Support, Non-U.S. Gov't;Anticonvulsants;Serotonin Antagonists;21 Neurophysiology;Receptors, AMPA;24 Pubmed search results 2008;21 Epilepsy;In Vitro;Animals;Receptors, N-Methyl-D-Aspartate;Cerebral Cortex;Microelectrodes;Corpus Callosum}, Medline = {98417597}, Month = {9}, Nlm_Id = {0370712}, Number = {1}, Organization = {Institute of Neurophysiology, University of D{\"u}sseldorf, D{\"u}sseldorf, D-40001, Germany.}, Pages = {113-22}, Pii = {S0014488698968376}, Pubmed = {9743572}, Title = {Pattern and pharmacology of propagating epileptiform activity in mouse cerebral cortex}, Uuid = {B6613555-40B8-4A61-BAB7-6CB919EC3C58}, Volume = {153}, Year = {1998}} @article{Alexanian:2001, Abstract = {These are the first studies to demonstrate that adult rat corticospinal tract (CST) neurons, which were identified by retrograde neuronal labeling, retain regenerative and proliferative potential. To determine if adult CST neurons undergo cell division, we tested if these retrogradely labeled cells synthesize DNA by adding BrdU to the cultures 24 h prior to fixation of the cells. The result shows that adult corticospinal tract neurons are capable of DNA synthesis, and our total cell counts with labeled cells counts further suggest that these cells undergo cell division.}, Author = {Alexanian, A. R. and Nornes, H. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cell Survival;Animals;Cells, Cultured;Rats;DNA;Rats, Sprague-Dawley;Neurites;Kinetics;Time Factors;Pyramidal Tracts;Nerve Regeneration;Axonal Transport;Male;Neurons;Cell Division;Immunohistochemistry;Bromodeoxyuridine;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {21369603}, Month = {8}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Colorado State University, Fort Collins, Colorado 80523, USA.}, Pages = {277-82}, Pii = {S0014488601977052}, Pubmed = {11476593}, Title = {Proliferation and regeneration of retrogradely labeled adult rat corticospinal neurons in culture}, Uuid = {5D82C2EE-3327-427B-B4AB-1C877CD67B23}, Volume = {170}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.2001.7705}} @article{Allen:1999, Abstract = {Malformations of cortical development are increasingly recognized as causes of mental retardation and epilepsy. However, little is known about the molecular and biochemical signals that control the proliferation, migration, and organization of the cells involved in normal cerebral cortical development. Analysis of genes required for cortical development will help elucidate the pathogenesis of some epilepsies. In humans, two striking examples of abnormal cortical development, with varying degrees of epilepsy and mental retardation, are 'double cortex' and lissencephaly. Double cortex (DC), also known as subcortical band heterotopia, shows an abnormal band of neurons in the white matter underlying a relatively normal cortex. In pedigrees, DC often occurs in females, whereas affected males show more severe lissencephaly (XLIS), i.e. an abnormally thick cortex with decreased or absent surface convolutions. We and others have identified a novel brain specific gene, doublecortin, that is mutated in Double Cortex/X-linked lissencephaly (DC/XLIS) patients. Although the cellular function of doublecortin (DCX) is unknown, sequence analysis reveals a cytoplasmic protein with potential MAP kinase phosphorylation sites, as well as a site that is likely to be phosphorylated by c-Abl, suggesting that doublecortin functions as an intracellular signaling molecule critical for the migration of developing neurons. Interestingly, the scrambler mouse mutant demonstrates abnormal lamination with some similarity to lissencephaly and reflects a mutation in the murine homolog of the Drosophila disabled gene, mdab1, which binds c-Abl. Although a direct interaction between doublecortin and mDab1 has not been demonstrated, it is plausible that these two proteins may be part of a common signaling pathway. Therefore, abnormalities in signal transduction may be an underlying mechanism for the neuronal migration defects in DC/XLIS and the scrambler mouse, but further research is necessary to determine how such abnormalities give rise to cortical malformations and epilepsy.}, Author = {Allen, K. M. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Signal Transduction;Animals;Humans;Mice, Mutant Strains;21 Epilepsy;review;Female;Epilepsy;Mutation;Cell Movement;Disease Models, Animal;Male;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;Neurons;Mice;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {99443185}, Month = {9}, Nlm_Id = {8703089}, Number = {2-3}, Organization = {Department of Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA.}, Pages = {143-54}, Pubmed = {10515162}, Title = {Genes that regulate neuronal migration in the cerebral cortex}, Uuid = {60015DC8-FAAA-47C8-BFDE-607144847E6E}, Volume = {36}, Year = {1999}} @article{Alonso:1999, Abstract = {In the adult rodent brain, it is now well established that neurons are continuously generated from proliferating neuronal progenitor cells located in the subventricular zone of the lateral ventricle (SVZ) and the dentate gyrus of the hippocampus. Recently, it has been shown that neurons can also be generated in vitro from various regions of the adult brain and spinal cord ventricular neuroaxis. As the highly polysialylated neural cell adhesion molecule (PSA-NCAM) has been shown to be specifically expressed by neuronal progenitor cells of the SVZ and the hippocampus, the present study was designed to determine whether cells expressing this molecule could be detected in the vicinity of the ventricular system of the adult rat brain and spinal cord. After double or triple immunostaining for different neuronal and glial markers, confocal microscopy was used to examine the surface of the ventricular neuroaxis in either 40- to 50-microm-thick transverse vibratome sections cut through different brain regions, or in 200- to 300-microm-thick tissue slices including the intact surface of the brain ventricles or of the spinal cord central canal. In untreated rats, PSA-NCAM, microtubule associated protein 2 (MAP2) and class III- beta-tubulin were found to be associated with a number of neuron-like cells located on the surface of the third and fourth ventricles and of the spinal cord central canal. The proliferation of the PSA-NCAM- immunoreactive (IR) neuron-like cells detected on the surface of the third and fourth ventricles was not affected by injection of epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) into these ventricles, but was stimulated by the combined injection of EGF + bFGF. These data indicate that cells exhibiting features of neuronal progenitors are present on the ependymal surface of the adult rat brain and spinal cord ventricular axis.}, Author = {Alonso, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Journal = {J Comp Neurol}, Keywords = {Fibroblast Growth Factor, Basic/pharmacology;Rats;Stem Cells/chemistry/*cytology;Neurons/chemistry/*cytology;Fourth Ventricle/chemistry/cytology;Spinal Canal/chemistry/cytology;02 Adult neurogenesis migration;Cell Division/drug effects/physiology;Central Nervous System/*cytology/physiology;Animal;Antimetabolites;Injections, Intraventricular;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;Sialic Acids/*analysis/metabolism;B;Neural Cell Adhesion Molecules/*analysis/metabolism;Age Factors;Rats, Sprague-Dawley/*physiology;Lateral Ventricles/chemistry/cytology;Third Ventricle/chemistry/cytology;Biological Markers;Bromodeoxyuridine}, Number = {2}, Organization = {INSERM U336, University of Montpellier II, 34095 Montpellier, France. galonso\@crit.univ-montp2.fr}, Pages = {149-66.}, Title = {Neuronal progenitor-like cells expressing polysialylated neural cell adhesion molecule are present on the ventricular surface of the adult rat brain and spinal cord}, Uuid = {92774D6C-F7E5-4CB5-A572-7948BE041489}, Volume = {414}, Year = {1999}, url = {papers/Alonso_JCompNeurol1999.pdf}} @article{Alonso:1999a, Abstract = {In the brain of adult rodents, young neurons arising from the subventricular zone (SVZ) of the lateral ventricle migrate tangentially along the rostral migratory stream (RMS) toward the olfactory bulb. The aim of this study was to determine whether surgical lesions placed through the RMS could affect the rostral migration of these newly formed neurons. Confocal and electron microscopy were used to characterize their anatomical organization within the intact and lesioned forebrains. As soon as 7 days and up to 45 days after placing a surgical lesion through the proximal portions of the RMS, numerous cells immunostained for polysialylated neural cell adhesion molecule (PSA-NCAM) were detected both (1) throughout the lesional cavity extending from the cortex to the anterior commissura, and (2) within the tissue located caudal to the lesion. In both regions, these PSA- NCAM-immunostained cells were labeled for neuronal markers but were negative for glial fibrillary acidic protein (GFAP). After administration of the proliferation marker bromodeoxyuridine (BrdU), nuclear labeling was associated with cells immunostained for PSA-NCAM but GFAP-negative, that accumulated within the lesional cavity and in the tissue caudal to the lesion. For the longest postlesional delays, a number of the PSA-NCAM-immunostained neurons located in various portions of the lesional cavity exhibited intense immunostaining for gamma-aminobutyric acid, whereas only a few of them exhibited faint immunostaining for tyrosine hydroxylase. These data indicate that surgical lesions placed through the RMS of adult rats impede the migration toward the olfactory bulb of the neuroblasts arising from the SVZ, inducing their accumulation and their partial differentiation in forebrain regions caudal to the lesion.}, Author = {Alonso, G. and Prieto, M. and Chauvet, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Cerebral Ventricles;B-13;24 Pubmed search results 2008;Immunohistochemistry;Sialic Acids;Male;Brain Diseases;Neural Cell Adhesion Molecule L1;Animals;Cell Movement;Brain Diseases/pathology/*physiopathology;Neural Cell Adhesion Molecules/metabolism;Neural Pathways;Microscopy, Electron;Sialic Acids/metabolism;Prosencephalon/pathology/*physiopathology;Animal;Neural Pathways/physiopathology;Rats, Sprague-Dawley;02 Adult neurogenesis migration;Prosencephalon;Rats;Cell Movement/physiology;Neurons/*physiology;Neural Cell Adhesion Molecules;Microscopy, Confocal;Support, Non-U.S. Gov't;Research Support, Non-U.S. Gov't;Neurons}, Medline = {99196578}, Month = {3}, Nlm_Id = {0406041}, Number = {4}, Organization = {INSERM U 336, Developpement, Plasticite et Vieillissement du Systeme Nerveux, Universite Montpellier II, Montpellier, France. galonso\@crit.univ-mont2.fr}, Pages = {508-28.}, Pii = {10.1002/(SICI)1096-9861(19990322)405:4<508::AID-CNE5>3.0.CO;2-5}, Pubmed = {10098942}, Title = {Tangential migration of young neurons arising from the subventricular zone of adult rats is impaired by surgical lesions passing through their natural migratory pathway}, Uuid = {796753F8-381C-476C-AAD7-8ACCC3B39794}, Volume = {405}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10098942%20Polaris:Users:ackman:Desktop:citmgr_endnote}} @article{Alonso:2001, Abstract = {Hundreds of thalamic axons ramify within a column of cat visual cortex; yet each layer 4 neuron receives input from only a fraction of them. We have examined the specificity of these connections by recording simultaneously from layer 4 simple cells and cells in the lateral geniculate nucleus with spatially overlapping receptive fields (n = 221 cell pairs). Because of the precise retinotopic organization of visual cortex, the geniculate axons and simple-cell dendrites of these cell pairs should have overlapped within layer 4. Nevertheless, monosynaptic connections were identified in only 33\%of all cases, as estimated by cross-correlation analysis. The visual responses of monosynaptically connected geniculate cells and simple cells were closely related. The probability of connection was greatest when a geniculate center overlapped a strong simple-cell subregion of the same sign (ON or OFF) near the center of the subregion. This probability was further increased when the time courses of the visual responses were similar. In addition, the connections were strongest when the simple-cell subregion and the geniculate center were matched in position, sign, and size. The rules of connectivity between geniculate afferents and simple cells resemble those found for retinal afferents to geniculate cells. The connections along the retinogeniculocortical pathway, therefore, show a precision that goes beyond simple retinotopy to include many other response properties, such as receptive-field sign, timing, subregion strength, and size. This specificity in wiring emphasizes the need for developmental mechanisms (presumably correlation-based) that can select among afferents that differ only slightly in their response properties.}, Author = {Alonso, J. M. and Usrey, W. M. and Reid, R. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;Photic Stimulation;research support, u.s. gov't, p.h.s. ;Visual Cortex;21 Neurophysiology;Cats;Action Potentials;research support, non-u.s. gov't ;Geniculate Bodies;Synaptic Transmission;Reaction Time;Animals;24 Pubmed search results 2008;Neurons;Signal Processing, Computer-Assisted}, Month = {6}, Nlm_Id = {8102140}, Number = {11}, Organization = {Laboratory of Neurobiology, The Rockefeller University, New York, New York 10021, USA. alonso\@uconnvm.uconn.edu}, Pages = {4002-15}, Pii = {21/11/4002}, Pubmed = {11356887}, Title = {Rules of connectivity between geniculate cells and simple cells in cat primary visual cortex}, Uuid = {FB7AEF4E-52D6-4D3D-9BD5-62D29FBA260D}, Volume = {21}, Year = {2001}, url = {papers/Alonso_JNeurosci2001.pdf}} @article{Alonso:2006, Abstract = {In the olfactory bulb (OB), new neurons are added throughout life, forming an integral part of the functioning circuit. Yet only some of them survive more than a month. To determine whether this turnover depends on olfactory learning, we examined the survival of adult newborn cells labeled with the cell division marker BrdU, administered before learning in an olfactory discrimination task. We report that discrimination learning increases the number of newborn neurons in the adult OB by prolonging their survival. Simple exposure to the pair of olfactory cues did not alter neurogenesis, indicating that the mere activation of sensory inputs during the learning task was insufficient to alter neurogenesis. The increase in cell survival after learning was not uniformly distributed throughout angular sectors of coronal sections of the OB. Monitoring odor activation maps using patterns of Zif268 immediate early gene expression revealed that survival was greater in regions more activated by the non-reinforced odorant. We conclude that sensory activation in a learning context not only controls the total number of newborn neurons in the adult OB, but also refines their precise location. Shaping the distribution of newborn neurons by influencing their survival could optimize the olfactory information processing required for odor discrimination.}, Author = {Alonso, Mariana and Viollet, C{\'e}cile and Gabellec, Marie-Madeleine M. and Meas-Yedid, Vannary and Olivo-Marin, Jean-Christophe C. and Lledo, Pierre-Marie M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Neurons;Odors;24 Pubmed search results 2008;Smell;Discrimination Learning;Female;research support, non-u.s. gov't ;Olfactory Receptor Neurons;Cell Survival;Animals, Newborn;Olfactory Bulb;Age Factors;comparative study ;Animals;Male;Mice}, Month = {10}, Nlm_Id = {8102140}, Number = {41}, Organization = {Perception and Memory Laboratory, Centre National de la Recherche Scientifique, Unit{\'e} de Recherche Associ{\'e}e 2182, Pasteur Institute, 75724 Paris Cedex 15, France.}, Pages = {10508-13}, Pii = {26/41/10508}, Pubmed = {17035535}, Title = {Olfactory discrimination learning increases the survival of adult-born neurons in the olfactory bulb}, Uuid = {315A7389-5006-429B-986D-CAAF64EA28A3}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2633-06.2006}} @article{Altman:1963, Author = {Altman, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Journal = {Anat. Rec.}, Keywords = {01 Adult neurogenesis general;10 Development;10 Hippocampus;A-1}, Pages = {573-591}, Title = {Autoradiographic investigation of cell proliferation in the brains of rats and cats}, Uuid = {20AF0C48-CD32-11D9-8C77-000D9346EC2A}, Volume = {145}, Year = {1963}} @article{Altman:1965, Abstract = {0021-9967 Journal Article}, Author = {Altman, J. and Das, G. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Comp Neurol}, Keywords = {Thymidine;01 Adult neurogenesis general;Cell Differentiation;10 Development;Testosterone/metabolism;Rats;10 Hippocampus;Autoradiography;A abstr;In Vitro;Hippocampus/*cytology/*growth &development;Animals, Newborn;Tritium;Animals}, Number = {3}, Pages = {319-35}, Pubmed = {5861717}, Title = {Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats}, Uuid = {20AF1206-CD32-11D9-8C77-000D9346EC2A}, Volume = {124}, Year = {1965}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5861717}} @article{Altman:1966, Author = {Altman, J. and Das, G. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:16 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Thymidine;Cerebellar Cortex;Limbic System;Rats;Medulla Oblongata;Geniculate Bodies;Cell Division;Hippocampus;Animals, Newborn;Spinal Cord;Animals;Cerebral Ventricles;Cerebral Cortex;Cochlear Nerve;Neurons}, Medline = {66141976}, Month = {3}, Nlm_Id = {0406041}, Number = {3}, Pages = {337-89}, Pubmed = {5937257}, Title = {Autoradiographic and histological studies of postnatal neurogenesis. I. A longitudinal investigation of the kinetics, migration and transformation of cells incorporating tritiated thymidine in neonate rats, with special reference to postnatal neurogenesis in some brain regions}, Uuid = {FBEC20D7-D067-11DA-8A8C-000D9346EC2A}, Volume = {126}, Year = {1966}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901260302}} @article{Altman:1969, Author = {Altman, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Comp Neurol}, Keywords = {Cell Differentiation;Basal Ganglia/growth &development;Rats;Thymidine;Ependyma/anatomy &histology/growth &development;Neurons/growth &development;Animal;Cerebral Ventricles/anatomy &histology/*growth &development;Corpus Callosum/growth &development;Time Factors;Limbic System/*growth &development;*Cell Movement;01 Adult neurogenesis general;A-1b;Methods;Neuroglia/growth &development;Brain/anatomy &histology/growth &development;Cerebral Cortex/growth &development;Tritium;Autoradiography}, Number = {4}, Pages = {433-57.}, Title = {Autoradiographic and histological studies of postnatal neurogenesis. IV. Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb}, Uuid = {20AF1015-CD32-11D9-8C77-000D9346EC2A}, Volume = {137}, Year = {1969}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=5361244}} @article{Altman:1990, Abstract = {Methacrylate-embedded sections and short-survival thymidine radiograms of the hippocampal dentate gyrus were examined in perinatal and postnatal rats in order to trace the site of origin and migration of the precursors of granule cells and study the morphogenesis of the granular layer. The densely packed, spindle-shaped cells of the secondary dentate matrix (a derivative of the primary dentate neuroepithelium) stream in a subpial position towards the granular layer of the internal dentate limb during the perinatal and early postnatal periods. By an accretionary process, the crest of the granular layer forms on day E21 and on the subsequent days the granular layer of the internal dentate limb expands progressively in a lateral direction. Granule cells differentiation, as judged by the transformation of polymorph, darkly staining small cells into rounder, lightly staining larger granule cells, follows the same gradient from the external dentate limb to the internal dentate limb. The secondary dentate matrix is in a process of dissolution by day P5. This matrix is the source of what will later become the outer shell of the granular layer composed of early generated granule cells. The thicker inner shell of the granular layer, formed during the infantile and juvenile periods, derives from an intrinsic, tertiary germinal matrix. On day E22, the dentate migration of the secondary dentate matrix becomes partitioned into two components: a) the subpial component of extradentate origin, referred to in this context as the first dentate migration, and b) the second dentate migration. The latter is distributed in the basal polymorph layer throughout the entire dentate gyrus and is henceforth recognized as the tertiary dentate matrix. The tertiary dentate matrix is prominent between days P3 and P10. It is postulated that the great increase in granule cell population during the infantile period is principally due to cells derived from this intrinsic matrix of the dentate gyrus. Between days P20 and P30 the tertiary dentate matrix disappears in the basal polymorph layer and henceforth proliferative cells become largely confined to the subgranular zone at the base of the granular layer. The subgranular zone is the source of granule cells produced during the juvenile and adult periods.}, Author = {Altman, J. and Bayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Aging;Gestational Age;Cell Differentiation;Thymidine;Rats;Hippocampus;Autoradiography;Cell Division;Tritium;Morphogenesis;Animals;Cell Movement;Rats, Inbred Strains}, Medline = {91086547}, Month = {11}, Multicitationkey = {b}, Nlm_Id = {0406041}, Notes = {Altman and Bayer 1990b}, Number = {3}, Organization = {Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.}, Pages = {365-81}, Pubmed = {2262596}, Title = {Migration and distribution of two populations of hippocampal granule cell precursors during the perinatal and postnatal periods}, Uuid = {4AFD248A-667B-11DA-A4B6-000D9346EC2A}, Volume = {301}, Year = {1990}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903010304}} @article{Altman:1990a, Abstract = {In radiograms of rat embryos that received a single dose of [3H]thymidine between days E16 and E20 and were killed 24 hours after the injection, the heavily labeled cells (those that ceased to multiply soon after the injection) form a horizontal layer in the intermediate zone of the hippocampus, called the inferior band. The fate of these heavily labeled cells was traced in radiograms of the dorsal hippocampus in embryos that received [3H]thymidine on day E18 and were killed at different intervals thereafter. Two hours after injection the labeled proliferative cells are located in the Ammonic neuroepithelium. The heavily labeled cells that leave the neuroepithelium and aggregate in the inferior band 1 day after the injection become progressively displaced toward the stratum pyramidale 2-3 days later, and penetrate the stratum pyramidale of the CA1 region on the 4th day. In the stratum pyramidale of the CA3 region, farther removed from the Ammonic neuroepithelium, the heavily labeled cells are still sojourning in the intermediate zone 4 days after labeling. Observations in methacrylate sections suggest that two morphogenetic features of the developing hippocampus may contribute to the long sojourn of young pyramidal cells in the intermediate zone: the way in which the stratum pyramidale forms and the way in which the alveolar channels develop. The stratum pyramidale of the CA1 region forms before that of the CA3 region, which is the reverse of the neurogenetic gradient in the production of pyramidal cells. We hypothesize that this is so because the pyramidal cells destined to settle in the CA3 region, which will be contacted by granule cells axons (the mossy fibers), have to await the formation of the granular layer on days E21-E22. Concordant with this is the observation that the hippocampal intermediate zone, which contains the sojourning young pyramidal cells, greatly enlarges between days E16 and E20, then suddenly diminishes and disappears by day E22. The other factor that may contribute to the prolonged sojourn of pyramidal cells, specifically those destined to settle in the CA1 region, is the pattern of alveolar channel development. This transient extracellular matrix begins to form several days after the onset of pyramidal cell neurogenesis, grows in a direction opposite to the settling of pyramidal cells in the stratum pyramidale, and does not reach the subicular end of Ammon's horn until day E21.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Altman, J. and Bayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Thymidine;Gestational Age;10 Development;Hippocampus;10 Hippocampus;Autoradiography;Rats;Comparative Study;Pyramidal Tracts;Tritium;Morphogenesis;Animals;Rats, Inbred Strains;Cerebral Cortex}, Medline = {91086546}, Month = {11}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.}, Pages = {343-64}, Pubmed = {2262595}, Title = {Prolonged sojourn of developing pyramidal cells in the intermediate zone of the hippocampus and their settling in the stratum pyramidale}, Uuid = {09B26CE0-212F-49E4-920F-12C6B941EA86}, Volume = {301}, Year = {1990}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903010303}} @article{Altman:1990b, Abstract = {This study deals with the site of origin, migration, and settling of the principal cell constituents of the rat hippocampus during the embryonic period. The results indicate that the hippocampal neuroepithelium consists of three morphogenetically discrete components--the Ammonic neuroepithelium, the primary dentate neuroepithelium, and the fimbrial glioepithelium--and that these are discrete sources of the large neurons of Ammon's horn, the smaller granular neurons of the dentate gyrus, and the glial cells of the fimbria. The putative Ammonic neuroepithelium is marked in short-survival thymidine radiograms by a high level of proliferative activity and evidence of interkinetic nuclear migration from day E16 until day E19. On days E16 and E17 a diffuse band of unlabeled cells forms outside the Ammonic neuroepithelium. These postmitotic cells are considered to be stratum radiatum and stratum oriens neurons, which are produced in large numbers as early as day E15. A cell-dense layer, the incipient stratum pyramidale, begins to form on day E18 and spindle-shaped cells can be traced to it from the Ammonic neuroepithelium. This migratory band increases in size for several days, then declines, and finally disappears by day E22. It is inferred that this migration contains the pyramidal cells of Ammon's horn that are produced mostly on days E17 through E20. The putative primary dentate neuroepithelium is distinguished from the Ammonic neuroepithelium during the early phases of embryonic development by its location, shape, and cellular dynamics. It is located around a ventricular indentation, the dentate notch, contains fewer mitotic cells near the lumen of the ventricle than the Ammonic neuroepithelium, and shows a different labeling pattern both in short-survival and sequential-survival thymidine radiograms. By day E18, the reduced primary dentate neuroepithelium is surrounded by an aggregate of proliferative cells; this is the secondary dentate matrix. On the subsequent days spindle-shaped cells that have retained their proliferative capacity migrate from the progressively receding secondary dentate matrix to the dentate gyrus itself. The latter, representing a tertiary germinal matrix, becomes highly active during the perinatal period. The putative fimbrial glioepithelium is situated between the primary dentate neuroepithelium and the tip of the hippocampal rudiment. Observations in methacrylate sections and thymidine radiograms suggest that the cells of this germinal matrix, unlike typical neuroepithelial cells, do not undergo interkinetic nuclear migration.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Altman, J. and Bayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Thymidine;Gestational Age;Rats;Epithelium;Hippocampus;Epithelial Cells;Autoradiography;Tritium;DNA Replication;Animals;Rats, Inbred Strains;Neurons}, Medline = {91086545}, Month = {11}, Multicitationkey = {a}, Nlm_Id = {0406041}, Notes = {Altman and Bayer 1990a}, Number = {3}, Organization = {Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907.}, Pages = {325-42}, Pubmed = {2262594}, Title = {Mosaic organization of the hippocampal neuroepithelium and the multiple germinal sources of dentate granule cells}, Uuid = {4AFD1BCC-667B-11DA-A4B6-000D9346EC2A}, Volume = {301}, Year = {1990}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903010302}} @article{Alvarez:2007, Abstract = {In excitatory neurons, most glutamatergic synapses are made on the heads of dendritic spines, each of which houses the postsynaptic terminal of a single glutamatergic synapse. We review recent studies demonstrating in vivo that spines are motile and plastic structures whose morphology and lifespan are influenced, even in adult animals, by changes in sensory input. However, most spines that appear in adult animals are transient, and the addition of stable spines and synapses is rare. In vitro studies have shown that patterns of neuronal activity known to induce synaptic plasticity can also trigger changes in spine morphology. Therefore, it is tempting to speculate that the plastic changes of spine morphology reflect the dynamic state of its associated synapse and are responsible to some extent for neuronal circuitry remodeling. Nevertheless, morphological changes are not required for all forms of synaptic plasticity, and whether changes in the spine shape and size significantly impact synaptic signals is unclear. Expected online publication date for the Annual Review of Neuroscience Volume 30 is June 16, 2007. Please see http://www.annualreviews.org/catalog/pub\_dates.asp for revised estimates.}, Author = {Alvarez, and Sabatini,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0147-006X}, Journal = {Annu Rev Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {7804039}, Organization = {Harvard Medical School, Department of Neurobiology, Boston, Massachusetts 02115 valvarez\@hms.harvard.edu.}, Pubmed = {17280523}, Title = {Anatomical and Physiological Plasticity of Dendritic Spines}, Uuid = {D6A0C8E2-17BA-48A9-8935-F9AC03B13D6F}, Year = {2007}, url = {papers/Alvarez_AnnuRevNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.30.051606.094222}} @article{Alvarez:2006, Abstract = {RNA interference (RNAi), which allows selective gene silencing, has been proposed for functional genomic analysis and for the treatment of human disease. However, induction of RNAi in mammalian cells by expression of double-stranded RNA can activate innate antiviral response pathways that perturb off-target gene expression. The activation and functional consequences of these effects in neurons are unknown. We find that expression of subsets of short hairpin RNAs (shRNAs) in rat hippocampal pyramidal neurons can have off-target effects that reduce the complexity of dendritic arbors and trigger the loss of dendritic spines. Morphological changes are accompanied by electrophysiological perturbations in passive membrane properties and a decrease in the number and strength of excitatory and inhibitory synapses. These perturbations depend on the shRNA sequence and are independent of the identity of the targeted protein. Our results indicate that off-target effects of RNAi severely perturb neuronal structure and function and may lead to the functional withdrawal of affected cells from the brain circuitry.}, Author = {Alvarez, Veronica A. and Ridenour, Dennis A. and Sabatini, Bernardo L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;Dendrites;Rats, Sprague-Dawley;21 Neurophysiology;Hippocampus;Rats;Nerve Tissue Proteins;23 RNAi;Research Support, N.I.H., Extramural;RNA Interference;Adaptation, Physiological;Cells, Cultured;Animals;24 Pubmed search results 2008;23 Technique;21 Epilepsy}, Month = {7}, Nlm_Id = {8102140}, Number = {30}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {7820-5}, Pii = {26/30/7820}, Pubmed = {16870727}, Title = {Retraction of synapses and dendritic spines induced by off-target effects of RNA interference}, Uuid = {FEC9AC84-48A4-11DB-A317-000D9346EC2A}, Volume = {26}, Year = {2006}, url = {papers/Alvarez_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1957-06.2006}} @article{Alvarez-Buylla:1992, Abstract = {Neurogenesis, typically a developmental phenomenon, continues into adult life in song birds. Cells born in the walls of the lateral ventricle migrate and differentiate throughout the adult telencephalon. I will argue here that birds take advantage of these new neurons as a form of plasticity. Most of the neurons connecting the different song control nuclei are born early in development. One important exception is the central efferent motor pathway for learned vocalization. This pathway is formed by projection neurons born during juvenile and adult life. Recruitment of new projection neurons at different times of the year and in different species correlates with vocal learning. Adult neurogenesis as a form of plasticity may serve learning and it may also teach us how to repair the damaged brain.}, Author = {Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Exp Neurol}, Keywords = {01 Adult neurogenesis general;Neurons/*physiology;Canaries/physiology;Brain/*physiology;*Neuronal Plasticity;A abstr;Animal;Support, U.S. Gov't, P.H.S.;Vocalization, Animal/physiology;Birds/*physiology;*Nerve Regeneration}, Number = {1}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {110-4.}, Pubmed = {1728556}, Title = {Neurogenesis and plasticity in the CNS of adult birds}, Uuid = {311B716B-7FC9-44B4-8489-E234E57C2632}, Volume = {115}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=1728556&dopt=Citation}} @article{Alvarez-Buylla:1990, Abstract = {Adult neurogenesis in birds offers unique opportunities to study basic questions addressing the birth, migration and differentiation of neurons. Neurons in adult canaries originate from discrete proliferative regions on the walls of the lateral ventricles. They migrate away from their site of birth, initially at high rates, along the processes of radical cells. The rates of dispersal diminish as the young neurons invade regions devoid of radial fibers, probably under the guidance of other cues. The discrete sites of birth in the ventricular zone generate neurons that end up differentiating throughout the telencephalon. New neurons may become interneurons or projection neurons; the latter connect two song control nuclei between neostriatum and archistriatum. Radial cells, that in mammals disappear as neurogenesis comes to an end, persist in the adult avian brain. The presence of radial cells may be key to adult neurogenesis. Not only do they serve as guides for initial dispersal, they also divide and may be the progenitors of new neurons.}, Author = {Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Experientia}, Keywords = {01 Adult neurogenesis general;Cell Differentiation;Cerebral Ventricles/cytology/growth &development;Telencephalon/cytology/embryology/growth &development;Birds/*growth &development;A abstr;Animal;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Cell Movement;Brain/cytology/*growth &development}, Number = {9}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {948-55.}, Pubmed = {2209804}, Title = {Mechanism of neurogenesis in adult avian brain}, Uuid = {93D98BA6-6D29-4C52-BFE2-2E6D52EC69EB}, Volume = {46}, Year = {1990}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=2209804&dopt=Citation}} @article{Alvarez-Buylla:1990a, Author = {Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Experientia}, Keywords = {*Cell Movement;02 Adult neurogenesis migration;Cell Differentiation;Brain/cytology/embryology/*growth &development;Animal;Neurons/*cytology;B abstr}, Number = {9}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {879-82.}, Pubmed = {2209795}, Title = {Commitment and migration of young neurons in the vertebrate brain}, Uuid = {D464D0CC-883F-488B-A1C4-BF461DCA6842}, Volume = {46}, Year = {1990}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=2209795&dopt=Citation}} @article{Alvarez-Buylla:1994, Abstract = {Neurogenesis occurs in adult song birds, which suggests that neurons born after hatching may contribute to histogenesis and plasticity of the avian brain. However, little is known about the overall contribution to the mature brain of neurons born in juveniles and adults, and how this process affects different regions of the avian brain. In fact, studies of the histogenesis of the avian forebrain have made the classical assumption that neuronal birth ends before hatching. Here we determined the contribution of neurons born before and after hatching to different regions throughout the adult canary brain. Male canaries were injected with [3H]-thymidine at different times during embryonic, juvenile, and adult life. The position of labeled neurons was mapped in parasagittal brain sections. Because all birds were killed as adults, results indicate the time of birth of neurons that survived to adulthood in different structures of the avian brain. Injection at embryonic day (E) 5 or E9 resulted in labeled neurons in all regions of the neuroaxis. The vast majority of neurons outside of the telencephalon were born before E9. One exception was a discrete region in the dorsal thalamus, a part of the song-control circuit, where neurons continued to be born after E9. Most regions of the telencephalon had a high proportion of its neurons labeled by the embryonic injections. In particular, archistriatum, anterior neostriatum, and the hippocampus had most of their neurons labeled before hatching. This indicates that many of the telencephalic neurons born in the embryo are long lived and are not replaced by other neurons that continue to be added to the telencephalon after hatching. Neurons labeled by [3H]-thymidine injections after hatching were restricted to the telencephalon and contributed importantly to many regions. In particular, the avian striatum (lobus parolfactorius, LPO) received a large number of its neurons during the first 20 days of life, but continued to incorporate new neurons throughout juvenile and adult life. Neurons continued to be added to the telencephalon of adults (even in 4-year-old birds). The distribution of labeled neurons after [3H]-thymidine injections in adults was similar to that observed in latter stages of juvenile development. The contribution of neurons born at different ages from embryonic development to adulthood varied among different anatomical subdivisions of the canary brain. this could, in part, explain differences in the cytoarchitecture and plasticity between brain regions. Neurogenesis after hatching may allow the modification of selected brain circuits as the bird matures and ages.}, Author = {Alvarez-Buylla, A. and Ling, C. Y. and Yu, W. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Comp Neurol}, Keywords = {Telencephalon/physiology;Neuronal Plasticity/physiology;Neurons/cytology/*physiology;Corpus Striatum/physiology;Animal;Cell Survival/physiology;Time Factors;Canaries/embryology/growth &development/*physiology;01 Adult neurogenesis general;Male;*Brain Mapping;Support, Non-U.S. Gov't;Embryo, Nonmammalian/cytology;Hippocampus/physiology;Support, U.S. Gov't, P.H.S.;Vocalization, Animal/*physiology;A abstr;Thalamic Nuclei/physiology}, Number = {2}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {233-48.}, Title = {Contribution of neurons born during embryonic, juvenile, and adult life to the brain of adult canaries: regional specificity and delayed birth of neurons in the song-control nuclei}, Uuid = {D8129FB6-6035-4968-BD94-8DDFAC283A9A}, Volume = {347}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7814666}} @article{Alvarez-Buylla:1992a, Abstract = {It is generally thought that most circuits of the adult central nervous system (CNS) are sculpted, in part at least, by selective elimination of some of the neurons present in an initial overabundant set. In this scenario, the birth of neurons precedes the period when brain functions, such as learning, first occur. In contrast to this form of brain assembly, we describe here the delayed development of the high vocal center (HVC) and one of its efferent pathways in canaries. The retrograde tracer Fluoro-Gold (FG) was injected into one of HVC's two efferent targets, the nucleus robustus archistriatalis (RA), to define the boundaries of HVC. The HVC grows markedly between 1 and 4 months, invading neighboring territories of the caudal telencephalon. During this same period, 0.43\%-0.64\%of the HVC neurons present at 1 year of age are labeled per day of [3H]-thymidine injection. [3H]-Thymidine labeling is a marker of cell birth, and during the first 4 months HVC neuron number increases, probably accounting for part of the HVC growth observed. Thereafter, the number of HVC neurons remains constant, but neuronal birth persists. We infer from this that neuronal replacement starts as early as 4 months after hatching and perhaps before then. About half of the neurons born after posthatching day 10 grow an axon to RA to form the main efferent pathway exiting from HVC. HVC growth, neurogenesis, axogenesis, and the observed replacement of neurons happen during the period of juvenile vocal learning. However, the recruitment of neurons that are still present at 1 year shows no particular inflections corresponding to the various stages in song learning, and continues at essentially the same rate after the more stereotyped adult song has been acquired. We suggest that a combination of neurogenesis and neuronal replacement provides unique advantages for learning.}, Author = {Alvarez-Buylla, A. and Ling, C. Y. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Neurobiol}, Keywords = {01 Adult neurogenesis general;Neuronal Plasticity/drug effects/physiology;Thymidine/pharmacology;Neurons/drug effects/*physiology;A abstr;Fluorescent Dyes;Animal;Support, U.S. Gov't, P.H.S.;Histocytochemistry;Birds/*physiology;Male;Efferent Pathways/cytology/drug effects/*growth &development;Vocalization, Animal/drug effects/*physiology}, Number = {4}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {396-406.}, Title = {High vocal center growth and its relation to neurogenesis, neuronal replacement and song acquisition in juvenile canaries}, Uuid = {C8FDE220-2941-4285-BA49-18308C5080D1}, Volume = {23}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/pubmed?term=1634887}} @article{Alvarez-Buylla:1997, Abstract = {Neurogenesis continues in the brain of adult birds. These cells are born in the ventricular zone of the lateral ventricles. Young neurons then migrate long distances guided, in part, by radial cell processes and become incorporated throughout most of the telencephalon. In songbirds, the high vocal center (HVC), which is important for the production of learned song, receives many of its neurons after hatching. HVC neurons which project to the robust nucleus of the archistriatum to form part of the efferent pathway for song production, and HVC interneurons continue to be added throughout life. In contrast, Area X-projecting HVC cells, thought to be part of a circuit necessary for song learning but not essential for adult song production, are only born in the embryo. New neurons in HVC of juvenile and adult birds replace older cells that die. There is a correlation between seasonal cell turnover rates (addition and loss) and testosterone levels in adult male canaries. Available evidence suggests that steroid hormones control the recruitment and/or survival of new HVC neurons, but not their production. The functions of neuronal replacement in adult birds remain unclear. However, rates of HVC neuron turnover are highest at times of year when canaries modify their songs. Replaceable HVC neurons may participate in the modification of perceptual memories or motor programs for song production. In contrast, permanent HVC neurons could hold long-lasting song-related information. The unexpected large-scale production of neurons in the adult brain holds important clues about brain function and, in particular, about the neural control of a learned behavior--birdsong.}, Author = {Alvarez-Buylla, A. and Kirn, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Neurobiol}, Keywords = {A;01 Adult neurogenesis general;Neurons/*physiology;Female;Cell Death/physiology;Animal;Brain/*cytology/*growth &development;Support, U.S. Gov't, P.H.S.;Birds/*physiology;Cell Movement/*physiology;Support, Non-U.S. Gov't;Vocalization, Animal/*physiology;Male}, Number = {5}, Organization = {Rockefeller University, New York, New York 10021, USA.}, Pages = {585-601.}, Title = {Birth, migration, incorporation, and death of vocal control neurons in adult songbirds}, Uuid = {934E17E6-72D5-4BAA-B293-E45AC691C1FE}, Volume = {33}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9369461}} @article{Alvarez-Buylla:1998, Author = {Alvarez-Buylla, A. and Temple, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {J Neurobiol}, Keywords = {Neurons/*physiology;02 Adult neurogenesis migration;B both;Embryo/physiology;Aging/physiology;Nervous System/cytology/*embryology/*growth &development;Animal;Support, U.S. Gov't, P.H.S.;Stem Cells/*physiology}, Number = {2}, Organization = {Rockefeller University, New York, New York 10021, USA.}, Pages = {105-10.}, Title = {Stem cells in the developing and adult nervous system}, Uuid = {4D7512D1-D06A-11DA-8A8C-000D9346EC2A}, Volume = {36}, Year = {1998}, url = {papers/Alvarez-Buylla_JNeurobiol1998.pdf}} @article{Alvarez-Buylla:1988, Abstract = {Frontal and coronal sections of adult male and female canary brain were stained with a monoclonal antibody to vimentin using an immunoperoxidase technique; some sections were counterstained with cresyl violet. The position of radial glia cells was mapped using a computer-linked microscope. The telencephalon was found to have a rich set of radial glia. The long processes of these radial glia showed a mediolateral orientation, and were much more abundant in some parts of the telencephalon (e.g., hyperstriatum, caudal neostriatum, and lobus parolfactorius) than in others (e.g., anterior neostriatum, archistriatum, and septum), which had few or no radial glia fibers. A small, elongated cell type not previously described in adult avian brain was frequently seen to be associated with the long processes of the radial glia, oriented in the same direction and often in close apposition. The position of these cells was also systematically mapped, and they were found to be virtually absent outside of the telencephalon. The relation between radial glia fibers and the small, elongated cells was most commonly seen close to the lateral ventricle of the forebrain, where the radial glia cells have their cell bodies. The above observations suggest that there may be a functional relation between radial glia and the small, elongated cells. We hypothesize that the latter cells are young migrating neurons. This hypothesis is tested in a separate publication (A. Alvarez-Buylla and F. Nottebohm, unpublished observations).}, Author = {Alvarez-Buylla, A. and Theelen, M. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Neurosci}, Keywords = {02 Adult neurogenesis migration;Neurons/*classification/cytology;Antibodies, Monoclonal/diagnostic use;03 Adult neurogenesis progenitor source;Female;Neuroglia/*cytology;Animal;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Birds/*anatomy &histology;Male;Brain/*cytology;BB abstr}, Number = {8}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {2707-12.}, Title = {Mapping of radial glia and of a new cell type in adult canary brain}, Uuid = {EE9962C0-1103-40F8-8E35-3B7D139ABA6C}, Volume = {8}, Year = {1988}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3411349}} @article{Alvarez-Buylla:1998a, Abstract = {New neurons continue to be born in the ventricular zone (VZ) of the lateral ventricles in the brain of adult birds. On the basis of serial section reconstruction and electron microscopy, we determined that the VZ of the adult canary brain is composed of three main cell types (A, B, and E). Type A cells were never found in contact with the ventricle and had microtubule-rich processes typical of young migrating neurons. Type B cells were organized as a pseudostratified epithelium, all contacted the ventricle, and most had a characteristic single cilium. Type E cells, also in contact with ventricle, were ultrastructurally similar to the mammalian multiciliated ependymal cells. After six injections of [3H]-thymidine (1 every 12 hr), Types A and B cells were found labeled. Type E cells were never [3H]-thymidine labeled. One to two hours after a single injection of [3H]-thymidine, all labeled cells corresponded to Type B cells. At survivals of 5, 24, and 74 hr after [3H]-thymidine injection, the proportion of labeled Type B cells decreased and that of Type A cells increased, indicating that Type B cells were the primary precursors. Most [3H]-labeled nuclei at 1-2 hr after [3H]-thymidine injection were separated from the ventricular cavity, but most of the mitotic cells were adjacent to the ventricle. This observation and measurements of the distance between labeled nuclei and the ventricular surface at 1, 5, 7, and 11 hr after [3H]- thymidine injection indicate that Type B cell nuclei move toward the ventricle to divide. This work reveals the architecture of the VZ in an adult vertebrate brain, identifies the primary precursor of new neurons, and describes nuclear translocation of these precursors during the cell cycle.}, Author = {Alvarez-Buylla, A. and Garcia-Verdugo, J. M. and Mateo, A. S. and Merchant-Larios, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {J Neurosci}, Keywords = {Cerebral Ventricles/*cytology;Cell Movement/*physiology;Neurons/*cytology/ultrastructure;Mitosis/physiology;Thymidine/pharmacokinetics;Female;Cell Count;02 Adult neurogenesis migration;Animal;Ependyma/*cytology;Cell Survival/physiology;03 Adult neurogenesis progenitor source;BB pdf;Canaries;Cell Division/physiology;Stem Cells/*cytology/ultrastructure;Cell Nucleus/physiology;Tritium/diagnostic use;Support, U.S. Gov't, P.H.S.;Age Factors;Microscopy, Electron;Cilia/ultrastructure}, Number = {3}, Organization = {The Rockefeller University Field Research Center, Tyrrel Road, Millbrook, New York 12545, USA.}, Pages = {1020-37.}, Title = {Primary neural precursors and intermitotic nuclear migration in the ventricular zone of adult canaries}, Uuid = {D08CA836-2B73-4C9B-B317-3D347D82CEE6}, Volume = {18}, Year = {1998}, url = {papers/Alvarez-Buylla_JNeurosci1998.pdf}} @article{Alvarez-Buylla:2002, Author = {Alvarez-Buylla, A. and Garcia-Verdugo, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;Astrocytes/cytology/physiology;Human;Neurons/*cytology/physiology;Regeneration/physiology;A both;Cell Differentiation/physiology;Animal;Lateral Ventricles/*cytology/growth &development;Support, U.S. Gov't, P.H.S.;Stem Cells/cytology/physiology;Support, Non-U.S. Gov't;Cell Movement/physiology}, Number = {3}, Organization = {Department of Neurological Surgery, Brain Tumor Research Center, San Francisco, California 94143-0520, USA. abuylla\@itsa.ucsf.edu}, Pages = {629-34.}, Title = {Neurogenesis in adult subventricular zone}, Uuid = {33573890-BF2C-45BC-A8AB-4969A6B33E00}, Volume = {22}, Year = {2002}, url = {papers/Alvarez-Buylla_JNeurosci2002.pdf}} @article{Alvarez-Buylla:2001, Abstract = {For many years, it was assumed that neurons and glia in the central nervous system were produced from two distinct precursor pools that diverged early during embryonic development. This theory was partially based on the idea that neurogenesis and gliogenesis occurred during different periods of development, and that neurogenesis ceased perinatally. However, there is now abundant evidence that neural stem cells persist in the adult brain and support ongoing neurogenesis in restricted regions of the central nervous system. Surprisingly, these stem cells have the characteristics of fully differentiated glia. Neuroepithelial stem cells in the embryonic neural tube do not show glial characteristics, raising questions about the putative lineage from embryonic to adult stem cells. In the developing brain, radial glia have long been known to produce cortical astrocytes, but recent data indicate that radial glia might also divide asymmetrically to produce cortical neurons. Here we review these new developments and propose that the stem cells in the central nervous system are contained within the neuroepithelial -->radial glia -->astrocyte lineage.}, Author = {Alvarez-Buylla, A. and Garcia-Verdugo, J. M. and Tramontin, A. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {Models, Biological;Astrocytes/cytology;B both;Aging;Embryo/cytology;Neuroglia/*cytology;Animal;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Epithelial Cells/cytology;Support, Non-U.S. Gov't;*Cell Lineage;Stem Cells/*cytology}, Number = {4}, Pages = {287-93.}, Title = {A unified hypothesis on the lineage of neural stem cells}, Uuid = {AD8AE0A4-A3E5-11DA-AB00-000D9346EC2A}, Volume = {2}, Year = {2001}, url = {papers/Alvarez-Buylla_NatRevNeurosci2001.pdf}} @article{Alvarez-Buylla:2001a, Abstract = {For many years, it was assumed that neurons and glia in the central nervous system were produced from two distinct precursor pools that diverged early during embryonic development. This theory was partially based on the idea that neurogenesis and gliogenesis occurred during different periods of development, and that neurogenesis ceased perinatally. However, there is now abundant evidence that neural stem cells persist in the adult brain and support ongoing neurogenesis in restricted regions of the central nervous system. Surprisingly, these stem cells have the characteristics of fully differentiated glia. Neuroepithelial stem cells in the embryonic neural tube do not show glial characteristics, raising questions about the putative lineage from embryonic to adult stem cells. In the developing brain, radial glia have long been known to produce cortical astrocytes, but recent data indicate that radial glia might also divide asymmetrically to produce cortical neurons. Here we review these new developments and propose that the stem cells in the central nervous system are contained within the neuroepithelial -->radial glia -->astrocyte lineage.}, Author = {Alvarez-Buylla, A. and Garcia-Verdugo, J. M. and Tramontin, A. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {Models, Biological;Astrocytes/cytology;02 Adult neurogenesis migration;Aging;Embryo/cytology;B both;03 Adult neurogenesis progenitor source;BB pdf;Neuroglia/*cytology;Animal;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Epithelial Cells/cytology;Support, Non-U.S. Gov't;*Cell Lineage;Stem Cells/*cytology}, Number = {4}, Organization = {Arturo Alvarez-Buylla and Anthony D. Tramontin are at the University of California, San Francisco, Department of Neurosurgery Research, Box 0520, Koret Vision Research Laboratories, K-130, 10 Kirkham Street, San Francisco, California 94143, USA.Jose Manuel Garcia-Verdugo is at the University of Valencia, Burjassot-46100, Valencia, Spain. abuylla\@itsa.ucsf.edu}, Pages = {287-293.}, Title = {OPINIONA unified hypothesis on the lineage of neural stem cells}, Uuid = {FE329AE0-0E35-4AE6-BE6B-CEA9E0E09AFF}, Volume = {2}, Year = {2001}, url = {papers/Alvarez-Buylla_NatRevNeurosci2001a.pdf}} @article{Alvarez-Buylla:1988a, Abstract = {Neurons are born in the ventricular walls of the vertebrate central nervous system. From there, the young neurons migrate to their final destinations, where differentiation occurs. Neuronal migration has been described during the ontogeny of the avian and mammalian brain. Whereas in mammals most neurogenesis occurs during early development, in the adult avian forebrain wide-spread neurogenesis continues to occur. How do neurons born in adulthood reach their final destination? We report here that small elongated cells, born in the ventricular zone adjacent to the lateral ventricle, differentiate into mature neurons 20-40 days later, after migrating over distances of up to 5 mm. Migration rates are highest (28 micron h-1) when young neurons migrate through regions which are rich in radial glia. The adult vertebrate brain offers unique opportunities for studying factors that regulate neuronal migration, pathfinding and differentiation.}, Author = {Alvarez-Buylla, A. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Nature}, Keywords = {02 Adult neurogenesis migration;Cell Differentiation;B;Brain/*growth &development;Neurons/*growth &development;Birds/*growth &development;Animal;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Cell Movement;Cerebral Ventricles/physiology}, Number = {6188}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {353-4.}, Title = {Migration of young neurons in adult avian brain}, Uuid = {798D18E0-0BB4-4E93-BBB4-8BEF61AD6F75}, Volume = {335}, Year = {1988}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3419503}} @article{Alvarez-Buylla:1990b, Abstract = {Neurogenesis in the adult avian brain is restricted to the telencephalon. New neurons originate in the ventricular zone (VZ) from cells that have not been identified. We mapped the position of [3H]thymidine-labeled cells in the walls of the ventricles of the adult canary brain. Labeled VZ cells were restricted to the telencephalon (lateral ventricles) and concentrated in "hot spots". The coincidence of these hot spots with regions rich in radial cells suggested that radial cells may be the cells undergoing mitosis. We used smears prepared from fragments of the VZ containing the hot spots to show directly that radial cells accumulate [3H]thymidine. In addition, grain counts at different survival times demonstrated that these cells divide. Hot spots of VZ cell division also coincided with sites of neuronal origin. We suggest that radial cell division may give rise to new neurons.}, Author = {Alvarez-Buylla, A. and Theelen, M. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Neuron}, Keywords = {02 Adult neurogenesis migration;03 Adult neurogenesis progenitor source;Female;Neurons/cytology/ultrastructure;Cell Division;Animal;Cerebral Ventricles/*cytology;Support, U.S. Gov't, P.H.S.;Thymidine/blood/diagnostic use;BB;Support, Non-U.S. Gov't;Birds/*anatomy &histology;Male}, Number = {1}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {101-9.}, Title = {Proliferation "hot spots"in adult avian ventricular zone reveal radial cell division}, Uuid = {AB1BFCF8-C194-4F64-8505-3DF168513375}, Volume = {5}, Year = {1990}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2369518}} @article{Alvarez-Buylla:2004, Abstract = {The adult mammalian brain retains neural stem cells that continually generate new neurons within two restricted regions: the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus subgranular zone (SGZ) of the hippocampus. Though these cellular populations are spatially isolated and subserve different brain systems, common themes begin to define adult neurogenic niches: (1) astrocytes serve as both stem cell and niche cell, (2) a basal lamina and concomitant vasculogenesis may be essential components of the niche, and (3) "embryonic"molecular morphogens and signals persist in these niches and play critical roles for adult neurogenesis. The adult neurogenic niches can be viewed as "displaced"neuroepithelium, pockets of cells and local signals that preserve enough embryonic character to maintain neurogenesis for life. 0896-6273 Journal Article}, Author = {Alvarez-Buylla, A. and Lim, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Neuron}, Keywords = {02 Adult neurogenesis migration;10 Development;BB pdf;03 Adult neurogenesis progenitor source;10 Hippocampus}, Number = {5}, Organization = {Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94143 USA. abuylla\@itsa.ucsf.edu}, Pages = {683-6}, Title = {For the long run: maintaining germinal niches in the adult brain}, Uuid = {F34EB901-698C-11DA-A4B6-000D9346EC2A}, Volume = {41}, Year = {2004}, url = {papers/Alvarez-Buylla_Neuron2004.pdf}} @article{Alvarez-Buylla:1988b, Abstract = {The higher vocal center (HVc) of the canary brain projects to two forebrain nuclei: robustus archistriatalis (RA) and area X of lobus parolfactorius. The time of birth of HVc neurons projecting to these two regions was determined by combining [3H]thymidine autoradiography and retrograde fluorogold uptake. Birds were sacrificed at 13 months of age, 4 days after fluorogold injections into area X or RA. A single injection of [3H]thymidine in ovo (embryonic day 9) labeled 76\%of area X-projecting cells and 0.8\%of cells projecting to RA. The great majority of RA-projecting cells were produced during posthatching development (posthatching day 10-240; P10-P240), with a peak at P60 and a hiatus at P120. HVc reaches full adult size by P240, yet at that age the production of new RA-projecting cells continued at a rate comparable to that recorded during posthatching development. Late production of neurons interconnecting two distant regions of the brain may regulate source to target cell population size. Male canaries start to sing at P40. During subsequent months, they imitate external models and their song becomes more structured and stereotyped. At sexual maturity (P240), song is stable. Three interpretations are offered: (i) neurogenesis of RA-projecting cells is related to learning, and learning continues even after achievement of pattern stability; (ii) neurogenesis of RA-projecting cells is not related to learning; (iii) the production of RA-projecting cells serves different purposes during development and after sexual maturity.}, Author = {Alvarez-Buylla, A. and Theelen, M. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Aging;01 Adult neurogenesis general;A;*Learning;Brain/embryology/growth &development/*physiology;Female;Neurons/cytology/*physiology;Animal;Support, U.S. Gov't, P.H.S.;DNA Replication;Canaries/*physiology;Support, Non-U.S. Gov't;Male;Vocalization, Animal}, Number = {22}, Organization = {Rockefeller University, Field Research Center, Millbrook, NY 12545.}, Pages = {8722-6.}, Title = {Birth of projection neurons in the higher vocal center of the canary forebrain before, during, and after song learning}, Uuid = {76FBD1F9-0919-4A63-8B35-A96C382CCDD1}, Volume = {85}, Year = {1988}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3186755}} @article{Alvarez-Buylla:2000, Abstract = {The subventricular zone (SVZ) is a major germinal zone which persists in the adult brain. The SVZ contains cells that self renew and continuously produce new neurons and glia. In this chapter we discuss the development, architecture and function of the adult SVZ, as well as the fate of SVZ cells after transplantation. We focus on identification of neural stem cells, factors which regulate neurogenesis and mechanisms for neuronal migration through the adult brain. Detailed understanding of these processes is necessary to utilize the SVZ as a source of neuronal and glial precursors for genetic manipulation, transplantation or brain self repair. Using Smart Source Parsing}, Author = {Alvarez-Buylla, A. and Herrera, D. G. and Wichterle, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Prog Brain Res}, Keywords = {Prosencephalon/cytology/*embryology/physiology;02 Adult neurogenesis migration;Cell Division/physiology;03 Adult neurogenesis progenitor source;Human;Stem Cells/cytology/physiology/*transplantation;Animal;Brain Injuries/*therapy;Neurons/cytology/physiology/*transplantation;Cell Differentiation/physiology;BB;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Age Factors;Cell Movement/physiology}, Organization = {Rockefeller University, 1230 York Avenue 210, New York, NY 10021, USA. alvarez\@rockvax.rockefeller.edu}, Pages = {1-11}, Title = {The subventricular zone: source of neuronal precursors for brain repair}, Uuid = {01E1CCC6-4B92-490D-82B9-FA7D4DD570B6}, Volume = {127}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11142024}} @article{Alvarez-Buylla:1990c, Abstract = {Projection neurons that form part of the motor pathway for song control continue to be produced and to replace older projection neurons in adult canaries and zebra finches. This is shown by combining [3H]thymidine, a cell birth marker, and fluorogold, a retrogradely transported tracer of neuronal connectivity. Species and seasonal comparisons suggest that this process is related to the acquisition of perceptual or motor memories. The ability of an adult brain to produce and replace projection neurons should influence our thinking on brain repair.}, Author = {Alvarez-Buylla, A. and Kirn, J. R. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Science}, Keywords = {A;01 Adult neurogenesis general;Neurons/*physiology;*Learning;Brain/*physiology;Axonal Transport;Autoradiography;Thymidine/metabolism;Animal;Canaries/*physiology;Tritium;Motor Activity;Support, U.S. Gov't, P.H.S.;Seasons;Vocalization, Animal}, Number = {4975}, Organization = {Rockefeller University Field Research Center, Millbrook, NY 12545.}, Pages = {1444-6.}, Title = {Birth of projection neurons in adult avian brain may be related to perceptual or motor learning}, Uuid = {EFD1758D-EEF4-4CF9-BE99-4B303A9D5A9F}, Volume = {249}, Year = {1990}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1698312}} @article{Alvarez-Buylla:1995, Abstract = {It is generally assumed that neurogenesis in the central nervous system ceases before or soon after birth. In the last three decades, however, several studies have reported that new neurons continue to be added into the brain of adult fish, frogs, reptiles, birds and mammals. The precursor cells that give rise to the neurons generated in adulthood are generally located in the walls of the brain ventricles. From these proliferative regions, neuronal precursors migrate toward their final targets where they differentiate; they often traverse long distances through complex brain parenchyma. The identity of the neuronal precursors in the brains of adult animals is still unknown. Experiments in adult birds suggest that proliferating radial cells may be the neuronal precursors. In adult mice, cells present in the subventricular zone can generated neurons in vivo and in vitro. These neuronal precursors can be induced to proliferate in vitro when exposed to growth factors and retain their potential to differentiate into neurons and glia. Whether these putative neural stem cells can differentiate into multiple neuronal types remains to be determined. The neuronal precursors of the adult brain could be used as a source of cells for neuronal transplantation. In addition, these cells could be manipulated in vivo or in vitro to introduce genes into the brain. Adult neurogenesis offers new experimental opportunities to study neuronal birth, migration and differentiation and for the treatment of neurological diseases.}, Author = {Alvarez-Buylla, A. and Lois, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Stem Cells}, Keywords = {Neurons/*physiology;02 Adult neurogenesis migration;Vertebrates/growth &development;B-4;*Stem Cells;Animal;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Brain/*cytology}, Number = {3}, Organization = {Rockefeller University, New York, New York 10021, USA.}, Pages = {263-72.}, Title = {Neuronal stem cells in the brain of adult vertebrates}, Uuid = {E4A85775-6132-444D-AB18-2AC9B6B51079}, Volume = {13}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7613493}} @article{Alvarez-Dolado:2003, Abstract = {Recent studies have suggested that bone marrow cells possess a broad differentiation potential, being able to form new liver cells, cardiomyocytes and neurons. Several groups have attributed this apparent plasticity to 'transdifferentiation'. Others, however, have suggested that cell fusion could explain these results. Using a simple method based on Cre/lox recombination to detect cell fusion events, we demonstrate that bone-marrow-derived cells (BMDCs) fuse spontaneously with neural progenitors in vitro. Furthermore, bone marrow transplantation demonstrates that BMDCs fuse in vivo with hepatocytes in liver, Purkinje neurons in the brain and cardiac muscle in the heart, resulting in the formation of multinucleated cells. No evidence of transdifferentiation without fusion was observed in these tissues. These observations provide the first in vivo evidence for cell fusion of BMDCs with neurons and cardiomyocytes, raising the possibility that cell fusion may contribute to the development or maintenance of these key cell types. 1476-4687 Journal Article}, Author = {Alvarez-Dolado, M. and Pardal, R. and Garcia-Verdugo, J. M. and Fike, J. R. and Lee, H. O. and Pfeffer, K. and Lois, C. and Morrison, S. J. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Nature}, Keywords = {Models, Biological;Purkinje Cells/*cytology;Cell Differentiation;EE pdf;Cell Fusion;Giant Cells/*cytology;Hepatocytes/*cytology;Myocytes, Cardiac/*cytology;Mice, Inbred C57BL;Bone Marrow Transplantation;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't;Stem Cells/cytology;Mice;Bone Marrow Cells/*cytology}, Number = {6961}, Organization = {Department of Neurological Surgery, University of California at San Francisco, San Francisco, California 94143-0520, USA.}, Pages = {968-73}, Title = {Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes}, Uuid = {0236AF83-CEDC-11D9-B244-000D9346EC2A}, Volume = {425}, Year = {2003}, url = {papers/Alvarez-Dolado_Nature2003.pdf}} @article{Alves:2002, Abstract = {In the early postnatal subventricular zone (SVZ), two seemingly unrelated events occur simultaneously: a massive tangential migration of neuroblasts towards the olfactory bulb, known as the rostral migratory stream (RMS), and the outward movement of radial glia (RG) undergoing astrocytic transformation. Because of the orthogonal arrangement between these two sets of cells, little, if any, relevance has been ascribed for their possible interactions. By depositing DiI at the pial surface we have studied RG transformation within the SVZ/RMS, from birth up to the end of the first postnatal week. While still within the SVZ/RMS, RG morphology changed from simple bipolar to highly complex branched profiles, attaining their highest degree of complexity at the interface of the SVZ with the overlying white matter. At this interface cell bodies of radial glia accumulate and their processes run tangentially, surrounding the SVZ/RMS. Processes of RG surrounding the SVZ/RMS could also be observed by immunostaining for vimentin, GFAP, and nestin. In contrast, in the white matter all DiI-labeled RG presented a simple bipolar profile. These results indicate that the outward radial migration of the transforming RG does not occur uniformly. Instead, the different morphologies and cell densities that RG assume when they cross the SVZ/RMS and overlying white matter imply different migratory behaviors. Finally, our data suggest that RG provide a cellular scaffold to the early postnatal SVZ/RMS, much in the same way as astrocytes in the adult RMS.}, Author = {Alves, Jos{\'e} A. J. and Barone, Patrick and Engelender, Simone and Fr{\'o}es, Maira M. and Menezes, Jo\~{a}o R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Cytoskeletal Proteins;Glial Fibrillary Acidic Protein;Cell Differentiation;Animals;Astrocytes;Rats;Cell Count;Cell Movement;Vimentin;Rats, Wistar;11 Glia;Olfactory Bulb;03 Adult neurogenesis progenitor source;Pia Mater;Animals, Newborn;Intermediate Filament Proteins;Carbocyanines;Stem Cells;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {22198992}, Month = {9}, Nlm_Id = {0213640}, Number = {3}, Organization = {Lab. de Neuroanatomia Celular, Departamento de Anatomia, Instituto de Ci\^{e}ncias Biom{\'e}dicas, Universidade Federal do Rio de Janeiro, Brazil 21941-590.}, Pages = {251-65}, Pubmed = {12210108}, Title = {Initial stages of radial glia astrocytic transformation in the early postnatal anterior subventricular zone}, Uuid = {FF999F5D-CAFD-4CAD-A1C9-054C2DD4B39F}, Volume = {52}, Year = {2002}, url = {papers/Alves_JNeurobiol2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.10087}} @article{Amadio:2006, Abstract = {Despite an ever-expanding database of sequenced mammalian genomes to be mined for clues, the emergence of the unique human brain remains an evolutionary enigma. In their new study, trawl the human genome and those of other mammals in search of short conserved DNA elements that show extremely rapid evolution only in humans. As they report in a recent issue of Nature, their scan yielded a gene for a novel noncoding RNA that adopts a human-specific structure and may regulate neurodevelopment.}, Author = {Amadio, and Walsh,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008;19 Neocortical evolution}, Month = {9}, Nlm_Id = {0413066}, Number = {6}, Organization = {Division of Genetics, Children's Hospital Boston, Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Broad Institute of MIT and Harvard, Boston, MA 02115, USA; Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Boston, MA 02115, USA.}, Pages = {1033-1035}, Pii = {S0092-8674(06)01154-8}, Pubmed = {16990130}, Title = {Brain Evolution and Uniqueness in the Human Genome}, Uuid = {376BC2C3-E835-4ABF-98E5-1337538DF0BE}, Volume = {126}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.09.007}} @article{Amendola:2005, Abstract = {Transferring multiple genes into the same cell allows for the combination of genetic correction, marking, selection and conditional elimination of transduced cells or the reconstitution of multisubunit components and synergistic pathways. However, this cannot be reliably accomplished by current gene transfer technologies. Based on the finding that some cellular promoters intrinsically promote divergent transcription, we have developed synthetic bidirectional promoters that mediate coordinate transcription of two mRNAs in a ubiquitous or a tissue-specific manner. Lentiviral vectors incorporating the new promoters enabled efficient dual gene transfer in several tissues in vivo after direct delivery or transgenesis, and in a human gene therapy model. Because divergent gene pairs, likely transcribed from shared promoters, are common in the genome, the synthetic promoters that we developed may mimic a well-represented feature of transcription. Vectors incorporating these promoters should increase the power of gene function studies and expand the reach and safety of gene therapy.}, Author = {Amendola, Mario and Venneri, Mary Anna and Biffi, Alessandra and Vigna, Elisa and Naldini, Luigi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {23 Technique}, Month = {1}, Nlm_Id = {9604648}, Number = {1}, Organization = {[1] San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy. [2] Vita Salute San Raffaele University, San Raffaele Scientific Institute, via Olgettina 58, 20132 Milano, Italy.}, Pages = {108-16}, Pii = {nbt1049}, Pubmed = {15619618}, Title = {Coordinate dual-gene transgenesis by lentiviral vectors carrying synthetic bidirectional promoters}, Uuid = {6A32CF1F-7CF6-45A9-9D29-3A0837FEDC48}, Volume = {23}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt1049}} @article{Amrein:2004, Abstract = {Abstract Adult neurogenesis in the dentate gyrus occurs at species-specific levels. Wood mice (Apodemus flavicollis) show higher proliferation rates than laboratory mice and voles (Clethrionomys glareolus, Microtus subterraneus). We compare rates of cell death and proliferation and investigate if cell proliferation leads to the long-term recruitment of granule cells. Granule and pyknotic cell numbers were estimated in wild-living rodents in different age classes and compared with laboratory mice of mixed genetic background. All species differ significantly in their number of granule cells, except for the comparison of laboratory mice with European pine voles. Granule cell number is significantly higher in old bank voles and wood mice as compared to adults (23 and 37\%, respectively). The number of pyknotic cells is highest in wood mice and lowest in laboratory mice. Across all species, the numbers of proliferating and pyknotic cells correlate. Despite differences in cell proliferation and cell death, the ratio of proliferating to pyknotic cells does not differ between adults of the wild-living species, but in laboratory mice a significantly lower proportion of cells die compared with the other species. In addition, the ratio of proliferating to pyknotic cells was significantly higher in old wood mice than in adults. We conclude (i) that cell proliferation can lead to an increase in granule cell number in wild-living rodents and (ii) that species- and age-specific changes of the ratio between proliferating and pyknotic cells occur as deviations from a close correlation of these two numbers across all species and age groups.}, Author = {Amrein, Irmgard and Slomianka, Lutz and Lipp, Hans-Peter P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {01 Adult neurogenesis general}, Month = {12}, Nlm_Id = {8918110}, Number = {12}, Organization = {Institute of Anatomy, University of Z{\"u}rich-Irchel, Winterthurerstr. 190, 8057 Z{\"u}rich, Switzerland.}, Pages = {3342-50}, Pii = {EJN3795}, Pubmed = {15610166}, Title = {Granule cell number, cell death and cell proliferation in the dentate gyrus of wild-living rodents}, Uuid = {678323BC-F18D-4E65-B48C-6B20A49DBDA9}, Volume = {20}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2004.03795.x}} @article{An:2004, Abstract = {Neurons communicate with one another through the release of molecules from synaptic vesicles and large dense core granules through the process of exocytosis. During exocytosis, molecules are released to the extracellular space through a fusion pore, which can either dilate, resulting in full fusion, or close, resulting in incomplete exocytosis, often referred to as 'kiss and run' exocytosis. Recently, there has been much interest in the regulation of this process in both neurons and neuroendocrine cells. There has been much recent work that addresses the existence of incomplete exocytosis in neurons and neuroendocrine cells, as well as recent work probing the molecular components and modulation of the fusion pore.}, Author = {An, Seong and Zenisek, David}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Synaptic Vesicles;research support, non-u.s. gov't;Central Nervous System;Secretory Vesicles;Exocytosis;Membrane Fusion;Presynaptic Terminals;Synaptic Transmission;research support, u.s. gov't, p.h.s.;Animals;Humans;Neurosecretory Systems;review;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9111376}, Number = {5}, Organization = {Yale University School of Medicine, Department of Cellular and Molecular Physiology, Sterling Hall of Medicine, B-147, 333 Cedar St, New Haven, Connecticut 06520, USA.}, Pages = {522-30}, Pii = {S0959-4388(04)00122-9}, Pubmed = {15464884}, Title = {Regulation of exocytosis in neurons and neuroendocrine cells}, Uuid = {ADF1D4B7-043E-4818-9FE9-EA1A6EA3259C}, Volume = {14}, Year = {2004}, url = {papers/An_CurrOpinNeurobiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2004.08.008}} @article{Andermann:2006, Abstract = {Most mammals possess high-resolution visual perception, with primary visual cortices containing fine-scale, inter-related feature representations (for example, orientation and ocular dominance). Rats lack precise vision, but their vibrissa sensory system provides a precise tactile modality, including vibrissa-related 'barrel' columns in primary somatosensory cortex. Here, we examined the subcolumnar organization of direction preference and somatotopy using a new omni-directional, multi-vibrissa stimulator. We discovered a direction map that was systematically linked to somatotopy, such that neurons were tuned for motion toward their preferred surround vibrissa. This sub-barrel column direction map demonstrated an emergent refinement from layer IV to layer II/III. These data suggest that joint processing of multiple sensory features is a common property of high-resolution sensory systems.}, Author = {Andermann, Mark L. and Moore, Christopher I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Electric Stimulation;Vibrissae;24 Pubmed search results 2008;Rats, Sprague-Dawley;research support, n.i.h., extramural ;21 Neurophysiology;Rats;research support, non-u.s. gov't ;research support, u.s. gov't, non-p.h.s. ;Brain Mapping;Models, Anatomic;Animals;Male;Motion Perception;Neurons;Somatosensory Cortex}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {Harvard Program in Biophysics, Medical School Campus, Building C-2 Room 122, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.}, Pages = {543-51}, Pii = {nn1671}, Pubmed = {16547511}, Title = {A somatotopic map of vibrissa motion direction within a barrel column}, Uuid = {02A0F3CF-4E63-49BA-BB4F-AC3CEFA3697E}, Volume = {9}, Year = {2006}, url = {papers/Andermann_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1671}} @article{Andermann:2004, Abstract = {The array of vibrissae on a rat's face is the first stage of a high-resolution tactile sensing system. Recently, it was discovered that vibrissae (whiskers) resonate when stimulated at specific frequencies, generating several-fold increases in motion amplitude. We investigated the neural correlates of vibrissa resonance in trigeminal ganglion and primary somatosensory cortex (SI) neurons (regular and fast spiking units) by presenting low-amplitude, high-frequency vibrissa stimulation. We found that somatosensory neurons showed band-pass tuning and enhanced sensitivity to small amplitude stimuli, reflecting the resonance amplification of vibrissa motion. Further, a putative somatotopic map of frequency selectivity was observed in SI, with isofrequency columns extending along the representations of arcs of vibrissae, in agreement with the gradient in vibrissa resonance across the vibrissa pad. These findings suggest several parallels between frequency processing in the vibrissa system and the auditory system and have important implications for detection and discrimination of tactile information.}, Author = {Andermann, Mark L. and Ritt, Jason and Neimark, Maria A. and Moore, Christopher I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Electric Stimulation;Trigeminal Ganglion;Vibrissae;research support, non-u.s. gov't;Rats, Sprague-Dawley;21 Neurophysiology;24 Pubmed search results 2008;Action Potentials;Rats;research support, u.s. gov't, non-p.h.s.;research support, u.s. gov't, p.h.s.;Animals;Male;Reaction Time;Neurons;Somatosensory Cortex}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139 USA.}, Pages = {451-63}, Pii = {S0896627304001989}, Pubmed = {15134641}, Title = {Neural correlates of vibrissa resonance; band-pass and somatotopic representation of high-frequency stimuli}, Uuid = {D1267E16-90BE-4F37-9169-9C817EA7EA82}, Volume = {42}, Year = {2004}, url = {papers/Andermann_Neuron2004.pdf}} @article{Andersen:1981, Abstract = {BALB/c mouse sarcoma virus (BALB-MSV) is a spontaneously occurring transforming retrovirus of mouse origin. The integrated form of the viral genome was cloned from the DNA of a BALB-MSV-transformed nonproducer NRK cell line in the Charon 9 strain of bacteriophage lambda. In transfection assays, the 19-kilobase-pair (kbp) recombinant DNA clone transformed NIH/3T3 mouse cells with an efficiency of 3 X 10(4) focus-forming units per pmol. Such transformants possessed typical BALB-MSV morphology and released BALB-MSV after helper virus superinfection. A 6.8-kbp DNA segment within the 19-kbp DNA possessed restriction enzyme sites identical to those of the linear BALB-MSV genome. Long terminal repeats of approximately 0.6 kbp were localized at either end of the viral genome by the presence of a repeated constellation of restriction sites and by hybridization of segments containing these sites with nick-translated Moloney murine leukemia virus long terminal repeat DNA. A continuous segment of at least 0.6 and no more than 0.9 kbp of helper virus-unrelated sequences was localized toward the 3' end of the viral genome in relation to viral RNA. A probe composed of these sequences detected six EcoRI-generated DNA bands in normal mouse cell DNA as well as a smaller number of bands in rat and human DNAs. These studies demonstrate that BALB-MSV, like previously characterized avian and mammalian transforming retroviruses, arose by recombination of a type C helper virus with a well-conserved cellular gene.}, Author = {Andersen, P. R. and Tronick, S. R. and Aaronson, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Mice, Inbred BALB C;Animals;Cloning, Molecular;Base Sequence;Transfection;15 Retrovirus mechanism;Sarcoma Viruses, Murine;Genes, Viral;Cell Line;DNA, Recombinant;Cell Transformation, Viral;Recombination, Genetic;Mice;DNA Restriction Enzymes;24 Pubmed search results 2008;Helper Viruses;Cell Transformation, Neoplastic;Nucleic Acid Hybridization}, Medline = {82101074}, Month = {11}, Nlm_Id = {0113724}, Number = {2}, Pages = {431-9}, Pubmed = {6275097}, Title = {Structural organization and biological activity of molecular clones of the integrated genome of a BALB/c mouse sarcoma virus}, Uuid = {20ACBDE9-5349-4945-BE83-D0E8656BFC20}, Volume = {40}, Year = {1981}} @article{Anderson:1999, Abstract = {Herein we review the evidence that neocortical projection neurons and interneurons are derived from distinct regions within the telencephalon. While neocortical projection neurons are derived from the ventricular zone of the neocortex, neocortical interneurons appear to be derived from the germinal zone of the basal ganglia. These interneurons follow a tangential migratory pathway from the ganglionic eminences to the cortex. Interneurons of the olfactory bulb follow a distinct tangential migration from the basal ganglia. The Dlx homeobox genes, which are essential for basal ganglia differentiation, are also required for the development of neocortical and olfactory bulb interneurons. Furthermore, evidence is presented that retroviral- mediated expression of DLX2 in neocortical cells can induce GABAergic interneuron differentiation.}, Author = {Anderson, S. and Mione, M. and Yun, K. and Rubenstein, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Cereb Cortex}, Keywords = {Mutagenesis/physiology;H;DNA-Binding Proteins/genetics;Cells, Cultured;Homeodomain Proteins/*genetics;Gene Expression Regulation, Developmental;Cell Movement/*physiology;Gene Expression Regulation, Viral;Phenotype;Animal;GABA/genetics;Recombinant Fusion Proteins;Retroviridae;Reverse Transcriptase Polymerase Chain Reaction;Neocortex/*cytology/*growth &development;Retroviridae Infections;Support, Non-U.S. Gov't;Cell Division/physiology;Support, U.S. Gov't, P.H.S.;Mice;Antisense Elements (Genetics);Cell Differentiation/physiology;12 Interneuron development;Interneurons/chemistry/*cytology}, Number = {6}, Organization = {Center for Neurobiology and Psychiatry, Department of Psychiatry, University of California at San Francisco, 94143-0984, USA.}, Pages = {646-54.}, Title = {Differential origins of neocortical projection and local circuit neurons: role of Dlx genes in neocortical interneuronogenesis}, Uuid = {5FB2B45E-FAA8-4D5F-9B98-9E731106FF96}, Volume = {9}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10498283}} @article{Anderson:2000, Abstract = {Recent studies directed toward developing a better understanding of the molecular and cellular biology basis of monocyte-derived multinucleated giant cell formation, function, and biologic activity are presented. In addition, HIV-1-infected T-lymphocyte syncytia and the significance of adhesion molecule/ligand interactions in the formation of these syncytia are described. Interleukin-4 or interleukin-13 induction of monocyte-macrophage fusion provides a model for foreign body giant cell formation. On the other hand, interferon-gamma induction of monocyte-macrophage fusion provides a model for Langhans' giant cell formation. Variations in monocyte-macrophage adhesion and fusion to form foreign body giant cells are provided by substrates with different surface chemistries. Recent advances in osteoclast biology have identified the role of tumor necrosis factor-alpha in regulating osteoclast bone resorption and receptor-ligand interactions and signal pathways for osteoclast activation. Although foreign body giant cells, Langhans' giant cells, and osteoclasts are derived from monocytes or monocyte progenitor cells, the ways in which they are formed, whether induced by cytokines, receptors, or biologic activity, are markedly different.}, Author = {Anderson, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1065-6251}, Journal = {Curr Opin Hematol}, Keywords = {Foreign Bodies;Giant Cells;HIV-1;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;CD4-Positive T-Lymphocytes;Humans;Animals;24 Pubmed search results 2008;Cell Lineage;review}, Medline = {20074202}, Month = {1}, Nlm_Id = {9430802}, Number = {1}, Organization = {Institute of Pathology, Case Western Reserve University, Cleveland, Ohio 44106, USA.}, Pages = {40-7}, Pubmed = {10608503}, Title = {Multinucleated giant cells}, Uuid = {BAD54022-E9E4-11DA-920C-000D9346EC2A}, Volume = {7}, Year = {2000}, url = {papers/Anderson_CurrOpinHematol2000.pdf}} @article{Anderson:1995, Abstract = {In C58 and AKR mice, endogenous N-tropic, ecotropic murine leukemia virus (MuLV) proviruses become activated in rare cells during embryogenesis. Resultant replication-competent progeny viruses then actively infect a large number of cells throughout the fetus, including cells in the developing central nervous system. By in situ hybridization analyses, we have assessed the presence of ecotropic MuLV RNA in the brains of C58 mice as a function of age. Only a few ecotropic MuLV-positive cells were observed in weanling mice, but the number of positive cells in the brain increased progressively with increasing age of the mice. Throughout the lives of the mice, the ecotropic MuLV RNA-positive cells were primarily located in well-defined white-matter tracts of the brain (commissura anterior, corpus callosum, fimbria hippocampi, optical tract, and striatum) and of the spinal cord. Cells of the subventricular zone also expressed ecotropic MuLV RNA, and in older mice a small number of positive cells were present in the grey matter. Infection of endogenous ecotropic MuLV provirus-less CE/J mice in utero with ecotropic MuLV clone AKR-623 resulted in the extensive infection of brain cells. The regional distribution of ecotropic MuLV RNA-containing cells was the same as observed in the brains of C58 mice, in which cells became infected by endogenously activated virus, but the number of positive cells was higher.}, Author = {Anderson, G. W. and Plagemann, P. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {RNA, Viral;Fetus;Pregnancy;Animals;Aging;Brain;Female;15 Retrovirus mechanism;Species Specificity;Virus Activation;Embryonic and Fetal Development;Leukemia Virus, Murine;Proviruses;Mice, Inbred Strains;Research Support, U.S. Gov't, P.H.S.;Mice;24 Pubmed search results 2008;15 ERVs retroelements;Mice, Inbred AKR;Research Support, Non-U.S. Gov't}, Medline = {96079065}, Month = {12}, Nlm_Id = {0113724}, Number = {12}, Organization = {Department of Microbiology, University of Minnesota, Minneapolis 55455, USA.}, Pages = {8089-95}, Pubmed = {7494328}, Title = {Expression of ecotropic murine leukemia virus in the brains of C58/M, DBA2/J, and in utero-infected CE/J mice}, Uuid = {833A10BF-4326-11DB-A5D2-000D9346EC2A}, Volume = {69}, Year = {1995}, url = {papers/Anderson_JVirol1995.pdf}} @article{Anderson:2001, Abstract = {0896-6273 Journal Article Review Review, Academic}, Author = {Anderson, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Neuron}, Keywords = {Body Patterning/*physiology;Neurons/cytology/metabolism;10 Development;Cell Differentiation/*physiology;Human;Gene Expression Regulation, Developmental/physiology;F;Stem Cells/cytology/*metabolism;Support, Non-U.S. Gov't;Animals;Nervous System/cytology/*embryology/growth &development;Stem Cell Transplantation}, Number = {1}, Organization = {Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. mancusog\@caltech.edu}, Pages = {19-35}, Pubmed = {11343642}, Title = {Stem cells and pattern formation in the nervous system: the possible versus the actual}, Uuid = {5AECD7C5-3713-4512-9D05-0B502E86ED91}, Volume = {30}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11343642}} @article{Anderson:1997, Abstract = {Although previous analyses indicate that neocortical neurons originate from the cortical proliferative zone, evidence suggests that a subpopulation of neocortical interneurons originates within the subcortical telencephalon. For example, gamma-aminobutyric acid (GABA)- expressing cells migrate in vitro from the subcortical telencephalon into the neocortex. The number of GABA-expressing cells in neocortical slices is reduced by separating the neocortex from the subcortical telencephalon. Finally, mice lacking the homeodomain proteins DLX-1 and DLX-2 show no detectable cell migration from the subcortical telencephalon to the neocortex and also have few GABA-expressing cells in the neocortex.}, Author = {Anderson, S. A. and Eisenstat, D. D. and Shi, L. and Rubenstein, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Science}, Keywords = {DNA-Binding Proteins/*genetics/physiology;Neocortex/*cytology/embryology/metabolism;H;Tissue Culture;Corpus Striatum/*cytology/embryology/metabolism;Animal;Cell Movement;Mutation;Glutamate Decarboxylase/metabolism;Calcium-Binding Protein, Vitamin D-Dependent/analysis;Support, Non-U.S. Gov't;Interneurons/chemistry/*physiology;GABA/analysis;Telencephalon/*cytology/embryology/metabolism;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Homeodomain Proteins/*genetics/physiology;Mice;*Genes, Homeobox;12 Interneuron development}, Number = {5337}, Organization = {Nina Ireland Laboratory of Developmental Neurobiology, Center for Neurobiology and Psychiatry, Department of Psychiatry, University of California at San Francisco, CA 94143-0984, USA.}, Pages = {474-6.}, Title = {Interneuron migration from basal forebrain to neocortex: dependence on Dlx genes}, Uuid = {15C1BDC3-6A4F-4628-A7F6-26DD68F2D423}, Volume = {278}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9334308}} @article{Andersson:2003, Abstract = {Immunologic reactions against gene therapy products may prove to be a frequent problem in clinical gene therapy protocols. Enhanced green fluorescence protein (EGFP) is commonly used as a marker in gene transfer protocols, and immune responses against EGFP-expressing cells have been documented. The present study was designed to investigate the effect of a pharmacologic, nonmyeloablative, conditioning regimen on the development of EGFP+ donor/recipient mixed bone marrow chimerism and ensuing tolerance to EGFP-expressing transplants. To this end, C57BL/6J (B6) mice were treated with soluble formulations of either busulfan (Busulfex) or the closely related compound treosulfan, followed by transplantation of bone marrow cells from EGFP-transgenic (B6-EGFP.Tg) donor mice. Such conditioning regimens resulted in long-term persistence of donor EGFP+ cells among various hematopoietic lineages from blood, bone marrow, and thymus. Stable hematopoietic chimeras transplanted at 10 to 17 weeks after bone marrow transplantation (BMT) with B6-EGFP.Tg skin grafts all accepted their transplants, whereas non-EGFP chimeric B6 control animals were able to mount rejection of the EGFP+ B6 skin grafts. Control third-party grafts from major histocompatibility complex (MHC)-mismatched mice were rejected within 20 days, indicating that acceptance of EGFP-expressing skin grafts was the result of specific immune tolerance induction by the transplantation of EGFP-transgenic bone marrow. Long-term tolerance to EGFP in chimeric recipients was confirmed by the absence of anti-EGFP-reactive T cells and antibodies. These results broaden the therapeutic potential for using hematopoietic molecular chimerism in nonmyeloablated recipients as a means of preventing rejection of genetically modified cells.}, Author = {Andersson, Goran and Illigens, Ben M. W. and Johnson, Kevin W. and Calderhead, David and LeGuern, Christian and Benichou, Gilles and White-Scharf, Mary E. and Down, Julian D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Transduction, Genetic;Animals;Bone Marrow Transplantation;Busulfan;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Immune Tolerance;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Gene Therapy;Skin Transplantation;Graft Rejection;Mice;Transplantation Conditioning;Luminescent Proteins;Graft Survival;Transgenes}, Medline = {22640656}, Month = {6}, Nlm_Id = {7603509}, Number = {11}, Organization = {BioTransplant Incorporated, Boston, MA 02129, USA.}, Pages = {4305-12}, Pii = {2002-06-1649}, Pubmed = {12576326}, Title = {Nonmyeloablative conditioning is sufficient to allow engraftment of EGFP-expressing bone marrow and subsequent acceptance of EGFP-transgenic skin grafts in mice}, Uuid = {5A39B7FD-2B5A-4633-884B-341E1BEBA5CA}, Volume = {101}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood-2002-06-1649}} @article{Andreadis:1997, Abstract = {Replication-incompetent recombinant retroviruses are currently used for gene delivery. The limited efficiency of gene transfer using these vectors hampers implementation of gene therapy. Successful integration of Moloney murine leukemia virus (MMuLV)-derived retroviral vectors into the host cell DNA requires cell division. The time difference between virus entry and cell division is variable and prolonged in slowly dividing cells. Therefore, the rate of intracellular decay of internalized vectors between the time of entry into the target cell and cell division may limit the probability of successful integration following viral entry. We present two methods that measure the intracellular stability of MMuLV-derived retroviral vectors in NIH 3T3 cells. The first is based on a temporary interruption of cell cycle progression by using cell detachment. This method provides an estimate, but not a direct measurement, of the half-life. The results show that the MMuLV intracellular half-life is on the order of but shorter than the total cell cycle time. The second method allows the direct measurement of the intracellular half-life by using two cell cycle-specific labels: 5-bromodeoxyuridine, a thymidine analog that labels cells in S-phase; and the viral vector that labels cells in mitosis. By varying the time between the administration of the two labels, the intracellular half-life is measured to be in the range of 5.5 to 7.5 h. Such a short intracellular half-life may restrict the efficiency of gene transfer by retroviral vectors, particularly in slowly dividing target cells.}, Author = {Andreadis, S. T. and Brott, D. and Fuller, A. O. and Palsson, B. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {beta-Galactosidase;Animals;Cell Cycle;15 Retrovirus mechanism;Kinetics;Trypsin;Genetic Vectors;Cell Adhesion;Half-Life;Gene Transfer Techniques;Moloney murine leukemia virus;3T3 Cells;Flow Cytometry;Mice;Virus Integration;Genes, Reporter;G1 Phase;S Phase}, Medline = {97456520}, Month = {10}, Nlm_Id = {0113724}, Number = {10}, Organization = {Department of Chemical Engineering, University of Michigan, Ann Arbor 48109, USA.}, Pages = {7541-8}, Pubmed = {9311834}, Title = {Moloney murine leukemia virus-derived retroviral vectors decay intracellularly with a half-life in the range of 5.5 to 7.5 hours}, Uuid = {2A31EBB9-5F7C-4795-9254-EB2B7779A40F}, Volume = {71}, Year = {1997}, url = {papers/Andreadis_JVirol1997.pdf}} @article{Andreassen:2001, Abstract = {A "spindle assembly"checkpoint has been described that arrests cells in G1 following inappropriate exit from mitosis in the presence of microtubule inhibitors. We have here addressed the question of whether the resulting tetraploid state itself, rather than failure of spindle function or induction of spindle damage, acts as a checkpoint to arrest cells in G1. Dihydrocytochalasin B induces cleavage failure in cells where spindle function and chromatid segregation are both normal. Notably, we show here that nontransformed REF-52 cells arrest indefinitely in tetraploid G1 following cleavage failure. The spindle assembly checkpoint and the tetraploidization checkpoint that we describe here are likely to be equivalent. Both involve arrest in G1 with inactive cdk2 kinase, hypophosphorylated retinoblastoma protein, and elevated levels of p21(WAF1) and cyclin E. Furthermore, both require p53. We show that failure to arrest in G1 following tetraploidization rapidly results in aneuploidy. Similar tetraploid G1 arrest results have been obtained with mouse NIH3T3 and human IMR-90 cells. Thus, we propose that a general checkpoint control acts in G1 to recognize tetraploid cells and induce their arrest and thereby prevents the propagation of errors of late mitosis and the generation of aneuploidy. As such, the tetraploidy checkpoint may be a critical activity of p53 in its role of ensuring genomic integrity. 1059-1524 Journal Article}, Author = {Andreassen, P. R. and Lohez, O. D. and Lacroix, F. B. and Margolis, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Mol Biol Cell}, Keywords = {Tubulin/metabolism;Human;Cyclin-Dependent Kinases/metabolism;Animals;Cytochalasin B/analogs &derivatives/*pharmacology;Cell Separation;Rats;*Polyploidy;Chromosomes/metabolism;Protein-Serine-Threonine Kinases/metabolism;*G1 Phase;08 Aberrant cell cycle;Immunoblotting;Actins/antagonists &inhibitors/metabolism;Cell Line;Support, Non-U.S. Gov't;*CDC2-CDC28 Kinases;Cyclins/metabolism;Mitotic Spindle Apparatus/*metabolism;*Cell Division/drug effects;Flow Cytometry;EE, T pdf;Mice;Enzyme Inhibitors/metabolism;Protein p53/*metabolism}, Number = {5}, Organization = {Institut de Biologie Structurale Jean-Pierre Ebel (Commissariat a l'Energie Atomique-Centre National de la Recherche Scientifique), 38027 Grenoble Cedex 1, France.}, Pages = {1315-28}, Title = {Tetraploid state induces p53-dependent arrest of nontransformed mammalian cells in G1}, Uuid = {88B57EDF-E9D9-41BE-AB71-A65993031201}, Volume = {12}, Year = {2001}, url = {papers/Andreassen_MolBiolCell2001.pdf}} @article{Ang:2003, Abstract = {We have used time-lapse multiphoton microscopy to map the migration and settling pattern of GABAergic interneurons that originate in the ganglionic eminence of the ventral forebrain and incorporate into the neocortex of the cerebral hemispheres. Imaging of the surface of the cerebral hemispheres in both explant cultures and brains of living mouse embryos revealed that GABAergic interneurons migrating within the marginal zone originate from three different sources and migrate via distinct and independent streams. After reaching their areal destination, interneurons descend into the underlying cortex to assume positions with isochronically generated, radially derived neurons. The dynamics and pattern of cell migration in the marginal zone (see movies, available at www.jneurosci.org) suggest that the three populations of interneurons respond selectively to distinct local cues for directing their migration to the appropriate areas and layers of the neocortex. This approach opens a new avenue for study of normal and abnormal neuronal migration in their native environment and indicate that interneurons have specific programs for their areal and laminar deployment. 1529-2401 Journal Article}, Author = {Ang, E. S. and Haydar, T. F. and Gluncic, V. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Neurosci}, Keywords = {Calcium-Binding Protein, Vitamin D-Dependent/biosynthesis;10 Development;Microscopy, Video/methods;Interneurons/*cytology/metabolism;gamma-Aminobutyric Acid/*metabolism;Immunohistochemistry;Bromodeoxyuridine/pharmacokinetics;Time Factors;In Vitro;Support, U.S. Gov't, P.H.S.;Cerebral Cortex/*cytology/*embryology;Animals;Support, Non-U.S. Gov't;Mice;F pdf;Cell Movement/physiology}, Number = {13}, Organization = {Department of Neurobiology, Yale Medical School, New Haven, Connecticut 06510, USA.}, Pages = {5805-15}, Pubmed = {12843285}, Title = {Four-dimensional migratory coordinates of GABAergic interneurons in the developing mouse cortex}, Uuid = {D46856EA-F2AC-4B79-AB02-167160A1A6BC}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12843285}} @article{Ang:2006, Abstract = {Epilepsy affects 1-2\%of the population, with temporal lobe epilepsy (TLE) the most common variant in adults. Clinical and experimental studies have demonstrated hippocampal involvement in the seizures underlying TLE. However, identification of specific functional deficits in hippocampal circuits associated with possible roles in seizure generation remains controversial. Significant attention has focused on anatomic and cellular alterations in the dentate gyrus. The dentate gyrus is a primary gateway regulating cortical input to the hippocampus and, thus, a possible contributor to the aberrant cortical-hippocampal interactions underlying the seizures of TLE. Alternate cortical pathways innervating the hippocampus might also contribute to seizure initiation. Despite this potential importance in TLE, these pathways have received little study. Using simultaneous voltage-sensitive dye imaging and patch-clamp recordings in slices from animals with epilepsy, we assessed the relative degree of synaptic excitation activated by multiple cortical inputs to the hippocampus. Surprisingly, dentate gyrus-mediated regulation of the relay of cortical input to the hippocampus is unchanged in epileptic animals, and input via the Schaffer collaterals is actually decreased despite reduction in Schaffer-evoked inhibition. In contrast, a normally weak direct cortical input to area CA1 of hippocampus, the temporoammonic pathway, exhibits a TLE-associated transformation from a spatially restricted, highly regulated pathway to an excitatory projection with >10-fold increased effectiveness. This dysregulated temporoammonic pathway is critically positioned to mediate generation and/or propagation of seizure activity in the hippocampus.}, Author = {Ang, Chyze W. and Carlson, Gregory C. and Coulter, Douglas A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Electric Stimulation;Pilocarpine;Animals;Rats;Neural Pathways;Muscarinic Agonists;Synaptic Transmission;Patch-Clamp Techniques;21 Epilepsy;Axons;Rats, Sprague-Dawley;Hippocampus;Organ Culture Techniques;research support, non-u.s. gov't;Male;Disease Models, Animal;Action Potentials;Cerebral Cortex;21 Neurophysiology;Epilepsy, Temporal Lobe;Dentate Gyrus;research support, n.i.h., extramural;Convulsants;24 Pubmed search results 2008;Neural Inhibition;Excitatory Postsynaptic Potentials}, Month = {11}, Nlm_Id = {8102140}, Number = {46}, Organization = {Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.}, Pages = {11850-6}, Pii = {26/46/11850}, Pubmed = {17108158}, Title = {Massive and specific dysregulation of direct cortical input to the hippocampus in temporal lobe epilepsy}, Uuid = {0ECDA66A-892D-45A3-BC1F-F59DAC504175}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2354-06.2006}} @article{Ang:2006a, Abstract = {Neurons of the cerebral neocortex in mammals, including humans, are generated during fetal life in the proliferative zones and then migrate to their final destinations by following an inside-to-outside sequence. The present study examined the effect of ultrasound waves (USW) on neuronal position within the embryonic cerebral cortex in mice. We used a single BrdU injection to label neurons generated at embryonic day 16 and destined for the superficial cortical layers. Our analysis of over 335 animals reveals that, when exposed to USW for a total of 30 min or longer during the period of their migration, a small but statistically significant number of neurons fail to acquire their proper position and remain scattered within inappropriate cortical layers and/or in the subjacent white matter. The magnitude of dispersion of labeled neurons was variable but systematically increased with duration of exposure to USW. These results call for a further investigation in larger and slower-developing brains of non-human primates and continued scrutiny of unnecessarily long prenatal ultrasound exposure.}, Author = {Ang, Eugenius S. B. C. and Gluncic, Vicko and Duque, Alvaro and Schafer, Mark E. and Rakic, Pasko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Embryo;24 Pubmed search results 2008;research support, n.i.h., extramural ;Ultrasonography;Female;Pregnancy;Animals;Cell Movement;Cerebral Cortex;Neurons;Mice}, Month = {8}, Nlm_Id = {7505876}, Number = {34}, Organization = {*Department of Neurobiology and Kavli Institute for Neuroscience, Yale Medical School, Sterling Hall of Medicine, Room C-318, 333 Cedar Street, New Haven, CT 06510.}, Pages = {12903-10}, Pii = {0605294103}, Pubmed = {16901978}, Title = {From the Cover: Prenatal exposure to ultrasound waves impacts neuronal migration in mice}, Uuid = {47E0A42B-2EF0-42A5-AFB1-8A2323EABF8A}, Volume = {103}, Year = {2006}, url = {papers/Ang_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0605294103}} @article{Angata:2007, Abstract = {Polysialic acid, which is synthesized by two polysialyltransferases, ST8SiaII and ST8SiaIV, plays an essential role in brain development by modifying the neural cell adhesion molecule (NCAM). It is currently unclear how polysialic acid functions in different processes of neural development. Here we generated mice doubly mutant in both ST8SiaII and ST8SiaIV to determine the effects of loss of polysialic acid on brain development. In contrast to NCAM-deficient, ST8SiaII-deficient, or ST8SiaIV-deficient single mutant mice, ST8SiaII and ST8SiaIV double mutants displayed severe defects in anatomical organization of the forebrain associated with apoptotic cell death. Loss of polysialic acid affected both tangential and radial migration of neural precursors during cortical development, resulting in aberrant positioning of neuronal and glial cells. Glial cell differentiation was aberrantly increased in vivo and in vitro in the absence of polysialic acid. Consistent with these findings, polysialic acid-deficient mice exhibited increased expression of the glial cell marker glial fibrillary acidic protein and a decrease in expression of Pax6, a transcription factor regulating neural cell migration. These results indicate that polysialic acid regulates cell migration and differentiation of neural precursors crucial for brain development.}, Author = {Angata, Kiyohiko and Huckaby, Valerie and Ranscht, Barbara and Terskikh, Alexey and Marth, Jamey D. and Fukuda, Minoru}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0270-7306}, Journal = {Mol Cell Biol}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8109087}, Number = {19}, Organization = {Glycobiology Program, Cancer Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.}, Pages = {6659-68}, Pii = {MCB.00205-07}, Pubmed = {17682066}, Title = {Polysialic acid-directed migration and differentiation of neural precursors are essential for mouse brain development}, Uuid = {ECB7B6ED-9301-43D1-AB15-9FC964CF5367}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/MCB.00205-07}} @article{Angelov:1998, Abstract = {This monograph reviews the literature and presents experimental data on the intracerebral presentation of antigen(s) to the immune system as a consequence of neuronal cell death. "Which cells are the antigen presenting cells (APC) of the brain?" is the main question of this book. The immune surveillance of the CNS occurs through specialized resident cells, which present (auto)antigen(s) to the immune system and thus initiate an (auto)immune response. There are four established prerequisites necessary to identify resident APC of the brain. First, the APC must be capable to phagocytose dead neurons. Second, in order to be recognized by T lymphocytes, these neuronophages must express Major Histocompatibility Complex (MHC) cells II glycoproteins on their surface. Third, in order to present (auto)antigen, the MHC class II-positive neuronophages must also be able to contact T lymphocytes. Fourth, in order to exert a stimulatory effect on T lymphocytes, the APC should be able to produce the cytokine interleukin-1 beta (IL-128 Mb). Three main tools were used to identify and characterize the APC of the brain. First, a lesion model was employed that yields a slowly progressing neuronal cell loss without disruption of the blood-brain barrier. This model consisted of resection of 10 mm of the facial nerve, which caused a slowly occurring neuronal death so that one year after resection the amount of facial neurons was about 44\%of the control value. Second, neuronophages were labeled in vivo in situ via phagocytosis of the permanent fluorescent marker Fluoro-Gold (FG) from decaying pre-loaded facial motoneurons. Third, the FG-labeled neuronophages were immunocytochemically characterized with the new method "immunoquenching of fluorescence". Sections of the brainstem containing FG-labeled, i.e. fluorescent, neuronophages were incubated with a variety of primary antibodies, followed by avidin-HRP and DAB-nickel as a dark brown reaction product for bright-field microscopy. In the fluorescent mode this DAB reaction product selectively quenches the fluorescence of all immunopositive cells, i.e. only those neuronophages that do not bind to the primary antibody remain fluorescent. Combining FG-labeling of neuronophages with immunoquenching, a population of small round fluorescent cells was discovered, localized in the immediate vicinity of the motoneurons long after the neuronofugal migration of microglia. As the fluorescence of these cells was not quenched after a triple immunostaining with anti-neuronal-specific enolase, anti-GFAP and OX-42 (quenching all fluorescence from neurons, astroglia, and microglia), they seem to represent a new, immunologically unidentified neuronophage. Following this triple immunostaining, a broad panel of antibodies was tested to stain, quench fluorescence, and thus immunotype these enigmatic phagocytes. Only the monoclonal antibody ED2, the classical marker for perivascular cells, specifically stained the small round neuronophages. Although the perivascular cells are in the vicinity of the basal lamina of the cerebral vasculature, they must not be confused with the pericytes, which are not able to perform phagocytosis. In contrast, the perivascular cells are macrophages-ED2 recognizes an established macrophage membrane antigen. In addition, after neuronal injury a subset of the perivascular cells starts to synthesize MHC class II glycoproteins and IL-1 beta. Hence this population of cells seems to possess the complete machinery required for antigen presentation: They are macrophages, upregulate MHC class II molecules and IL-1 beta, and due to their anatomical location, have access to circulating T lymphocytes. What was still lacking, however, was a direct proof of neuronophagia. Our experiments provided this proof. (ABSTRACT TRUNCATED)}, Author = {Angelov, D. N. and Walther, M. and Streppel, M. and Guntinas-Lichius, O. and Neiss, W. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0301-5556}, Journal = {Adv Anat Embryol Cell Biol}, Keywords = {Research Support, Non-U.S. Gov't;Facial Nerve;Blood-Brain Barrier;11 Glia;Cerebrovascular Circulation;Animals;Brain;review}, Medline = {99033513}, Nlm_Id = {0407712}, Organization = {Institut f{\"u}r Anatomie der Universit{\"a}t zu K{\"o}ln, Germany.}, Pages = {1-87}, Pubmed = {9816725}, Title = {The cerebral perivascular cells}, Uuid = {D241189A-3E70-4A33-9C7E-0EAEA9CA4CC1}, Volume = {147}, Year = {1998}} @article{Angevine:1961, Author = {Angevine, J. B. and Sidman, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Journal = {Nature}, Keywords = {A, F abstr}, Pages = {766-768}, Title = {Autoradiographic study of cell migration during histogenesis of cerebral cortex in the mouse}, Uuid = {2A0FC100-CDF0-11D9-B244-000D9346EC2A}, Volume = {192}, Year = {1961}} @article{Anthony:2004, Abstract = {Radial glial cells function during CNS development as neural progenitors, although their precise contribution to neurogenesis remains controversial. Recent work has argued that regional differences may exist regarding the neurogenic potential of radial glia. Here, we show that the vast majority of neurons in all brain regions derive from radial glia. Cre/loxP fate mapping and clonal analysis demonstrate that radial glia throughout the CNS serve as neuronal progenitors and that radial glia within different regions of the CNS pass through their neurogenic stage of development at distinct time points. Thus, radial glial populations within different CNS regions are not heterogeneous with regard to their potential to generate neurons versus glia. 0896-6273 Journal Article}, Author = {Anthony, T. E. and Klein, C. and Fishell, G. and Heintz, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Neuron}, Keywords = {F, G pdf}, Number = {6}, Organization = {Laboratory of Molecular Biology, Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021 USA.}, Pages = {881-90}, Title = {Radial glia serve as neuronal progenitors in all regions of the central nervous system}, Uuid = {BCAB79E0-71C2-11DA-A383-000D9346EC2A}, Volume = {41}, Year = {2004}, url = {papers/Anthony_Neuron2004.pdf}} @article{Antimoni:1980, Abstract = {Effect of the modulated electromagnetic field (MEMF) on the experimentally evoked epileptiform activity of the brain structures was studied. The effect of MEMF of 2-30 hz was shown to induce suppression of the brain epileptiform activity in 41\%of the experiments. The epileptiform activity was markedly decreased in 23\%and potentiated in 10\%of the experiments, while in 25\%of the experiments the MEMF effect did not essentially change the pattern of the evoked epileptiform brain activity.}, Author = {Antimoni, G. D. and Salamov, R. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0365-9615}, Journal = {Biull Eksp Biol Med}, Keywords = {21 Epilepsy;Electroencephalography;21 Neurophysiology;Rats;Female;Electromagnetics;English Abstract;Seizures;Evoked Potentials;Acoustic Stimulation;Reaction Time;Animals;Electromagnetic Fields;24 Pubmed search results 2008;Brain;Male}, Medline = {80175731}, Month = {2}, Nlm_Id = {0370627}, Number = {2}, Pages = {145-8}, Pubmed = {7370408}, Title = {[Action of a modulated electromagnetic field on experimentally induced epileptiform brain activity in rats]}, Uuid = {52096B70-B7BB-4BCA-A4C4-6BB0F6D1E081}, Volume = {89}, Year = {1980}} @article{Anton:2004, Abstract = {Neural progenitor proliferation, differentiation and migration are continually active in the rostral migratory stream of the adult brain. Here, we show that the receptor tyrosine kinase ErbB4 is expressed prominently by the neuroblasts present in the subventricular zone and the rostral migratory stream. The neuregulins (NRG1-NRG3), which have been identified as ErbB4 ligands, are detected either in the stream or in adjacent regions. Mice deficient in ErbB4 expressed under the control of either the nestin or the hGFAP promoter have altered neuroblast chain organization and migration and deficits in the placement and differentiation of olfactory interneurons. These findings suggest that ErbB4 activation helps to regulate the organization of neural chains that form the rostral migratory stream and influences the differentiation of olfactory interneuronal precursors.}, Author = {Anton, and Ghashghaei, and Weber, and McCann, and Fischer, and Cheung, and Gassmann, and Messing, and Klein, and Schwab, and Lloyd, and Lai,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {02 Adult neurogenesis migration}, Nlm_Id = {9809671}, Organization = {[1] UNC Neuroscience Center and the Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA. [2] These authors contributed equally to this work.}, Pii = {nn1345}, Pubmed = {15543145}, Title = {Receptor tyrosine kinase ErbB4 modulates neuroblast migration and placement in the adult forebrain}, Uuid = {8D2509BA-DC5E-4AA8-A5B4-7AB29E45E01E}, Year = {2004}, url = {papers/Anton_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1345}} @article{Anton:1999, Abstract = {Changes in specific cell-cell recognition and adhesion interactions between neurons and radial glial cells regulate neuronal migration as well as the establishment of distinct layers in the developing cerebral cortex. Here, we show that alpha3beta1 integrin is necessary for neuron-glial recognition during neuronal migration and that alpha(v) integrins provide optimal levels of the basic neuron-glial adhesion needed to maintain neuronal migration on radial glial fibers. A gliophilic-to-neurophilic switch in the adhesive preference of developing cortical neurons occurs following the loss of alpha3beta1 integrin function. Furthermore, the targeted mutation of the alpha3 integrin gene results in abnormal layering of the cerebral cortex. These results suggest that alpha3beta1 and alpha(v) integrins regulate distinct aspects of neuronal migration and neuron-glial interactions during corticogenesis.}, Author = {Anton, E. S. and Kreidberg, J. A. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Integrin alpha3beta1;Animals;Integrins;Research Support, U.S. Gov't, Non-P.H.S.;Integrin alphaV;Mutation;Antigens, CD;Cell Movement;Embryonic and Fetal Development;Embryo;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neuroglia;Cell Aggregation;Neurons;Integrin alpha3;Mice;Research Support, Non-U.S. Gov't}, Medline = {99166864}, Month = {2}, Nlm_Id = {8809320}, Number = {2}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510-8001, USA. esa5\@psu.edu}, Pages = {277-89}, Pii = {S0896-6273(00)81089-2}, Pubmed = {10069334}, Title = {Distinct functions of alpha3 and alpha(v) integrin receptors in neuronal migration and laminar organization of the cerebral cortex}, Uuid = {AC9B3ADF-E3D7-4E4D-BFCA-3EAAD7518A98}, Volume = {22}, Year = {1999}, url = {papers/Anton_Neuron1999.pdf}} @article{Antonini:1998, Abstract = {To investigate the possible anatomical basis for the functional recovery of visual cortical responses after reverse monocular deprivation, we have studied the morphology of single geniculocortical afferents to area 17. In kittens reverse-sutured for 10 d after an initial week of monocular deprivation, single-unit and intrinsic signal optical recordings confirmed that the effects of the initial deprivation were largely reversed. Responses through the originally nondeprived (OND) eye were drastically diminished, but remained much more selective for orientation than after an initial monocular deprivation (Crair et al., 1997). Responses through the originally deprived (OD) eye recovered completely. Geniculocortical afferent arbors in layer IV of area 17 were filled by iontophoresis of Phaseolus lectin into lamina A of the lateral geniculate nucleus (LGN) and were serially reconstructed. Arbors serving both the OD and the OND eye were analyzed. The plastic changes of both OD and OND arbors were evaluated by comparison with arbors reconstructed in normal animals and in animals studied after an equivalent initial period of deprivation (Antonini and Stryker, 1996). These analyses demonstrate that closure of the OND eye caused a substantial shrinkage of the arbors serving that eye. Moreover, reopening the OD eye induced regrowth only in some arbors, whereas others appeared to be largely unaffected and continued to have the characteristics of deprived arbors. Quantitatively, the initial and the second deprivation caused similar proportional changes in total arbor length and numbers of branches, whereas several other features were more severely affected by the initial deprivation.}, Author = {Antonini, A. and Gillespie, D. C. and Crair, M. C. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-27 11:35:53 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Electrophysiology;Animals;Sutures;Visual Pathways;Sensory Deprivation;Neurons, Afferent;Vision, Monocular;Axons;Critical Period (Psychology);Dendrites;Nerve Regeneration;Cell Size;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008;Visual Cortex;Cats;Geniculate Bodies;Phytohemagglutinins; 21 Activity-development}, Month = {12}, Nlm_Id = {8102140}, Number = {23}, Organization = {W. M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, California 94143-0444, USA.}, Pages = {9896-909}, Pubmed = {9822746}, Title = {Morphology of single geniculocortical afferents and functional recovery of the visual cortex after reverse monocular deprivation in the kitten}, Uuid = {32EB0FC4-6F63-4549-A13B-E89CE108FB3D}, Volume = {18}, Year = {1998}} @article{Antony:2004, Abstract = {Human endogenous retroviruses (HERVs) constitute 8\%of the human genome and have been implicated in both health and disease. Increased HERV gene activity occurs in immunologically activated glia, although the consequences of HERV expression in the nervous system remain uncertain. Here, we report that the HERV-W encoded glycoprotein syncytin is upregulated in glial cells within acute demyelinating lesions of multiple sclerosis patients. Syncytin expression in astrocytes induced the release of redox reactants, which were cytotoxic to oligodendrocytes. Syncytin-mediated neuroinflammation and death of oligodendrocytes, with the ensuing neurobehavioral deficits, were prevented by the antioxidant ferulic acid in a mouse model of multiple sclerosis. Thus, syncytin's proinflammatory properties in the nervous system demonstrate a novel role for an endogenous retrovirus protein, which may be a target for therapeutic intervention.}, Author = {Antony, Joseph M. and van Marle, Guido and Opii, Wycliffe and Butterfield, D. Allan and Mallet, Fran\c{c}ois and Yong, Voon Wee and Wallace, John L. and Deacon, Robert M. and Warren, Kenneth and Power, Christopher}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Gene Products, env;Multiple Sclerosis;Myelin Sheath;Astrocytes;Encephalitis;Rats;Antioxidants;Middle Aged;Humans;Animals;Coumaric Acids;Oligodendroglia;15 Retrovirus mechanism;Endogenous Retroviruses;Recombinant Fusion Proteins;RNA, Messenger;Disease Models, Animal;Oxidation-Reduction;Aged;Cell Line;Adult;Reactive Oxygen Species;Pregnancy Proteins;Mice;24 Pubmed search results 2008;Cell Death;15 ERVs retroelements;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada.}, Pages = {1088-95}, Pii = {nn1319}, Pubmed = {15452578}, Title = {Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination}, Uuid = {3A64ADE8-EE5A-11DA-8605-000D9346EC2A}, Volume = {7}, Year = {2004}, url = {papers/Antony_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1319}} @article{Aoki:2007, Abstract = {Although context-dependent spike synchronization among populations of neurons has been experimentally observed, its functional role remains controversial. In this modeling study, we demonstrate that in a network of spiking neurons organized according to spike-timing-dependent plasticity, an increase in the degree of synchrony of a uniform input can cause transitions between memorized activity patterns in the order presented during learning. Furthermore, context-dependent transitions from a single pattern to multiple patterns can be induced under appropriate learning conditions. These findings suggest one possible functional role of neuronal synchrony in controlling the flow of information by altering the dynamics of the network.}, Author = {Aoki, Takaaki and Aoyagi, Toshio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0899-7667}, Journal = {Neural Comput}, Keywords = {research support, non-u.s. gov't;Neural Networks (Computer);21 Neurophysiology;Action Potentials;Neuronal Plasticity;Memory;Learning;Reaction Time;Animals;Humans;24 Pubmed search results 2008;Neurons}, Month = {10}, Nlm_Id = {9426182}, Number = {10}, Organization = {Graduate School of Informatics, Kyoto University, Kyoto 606-8501, Japan. aoki\@acs.i.kyoto-u.ac.jp}, Pages = {2720-38}, Pubmed = {17716009}, Title = {Synchrony-induced switching behavior of spike pattern attractors created by spike-timing-dependent plasticity}, Uuid = {9C607E0B-DCF3-470B-BB96-29198879EF69}, Volume = {19}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1162/neco.2007.19.10.2720}} @article{Aram:1988, Abstract = {A simple slice chamber was designed to achieve easy manipulations of temperature, ionic composition and drug concentrations. Spontaneous and evoked extracellular potentials could be recorded with glass microelectrodes from 500 micron thick slices of rat frontal neocortex. In the absence of magnesium ions in the superfusing medium or in the presence of convulsant agents, epileptiform activity was seen. The amplitude of this activity was greatest in layer II/III, each burst consisting of a long-lasting negative potential on the decay phase of which were superimposed many afterpotentials. There were multiple foci from which spontaneous epileptiform bursts spread to other ipsi- and contralateral parts of the cortex via both the grey and white matter. Although such bursts were observed between 23 and 37 degrees C, optimal recording of discrete epileptiform activity was achieved at 29 +/- 1 degrees C. Decreasing extracellular calcium or increasing extracellular concentrations of potassium enhanced burst discharges. Proconvulsant agents initiated both interictal and ictal epileptiform events. This, together with the reduction of epileptiform activity by standard anticonvulsant drugs such as carbamazepine and phenobarbitone suggested that this in vitro model may be useful for studying the pharmacology of epileptogenesis and for developing new therapeutic strategies for epilepsy.}, Author = {Aram, J. A. and Lodge, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Research Support, Non-U.S. Gov't;Electric Stimulation;Animals;In Vitro;Evoked Potentials;Rats;21 Epilepsy;Female;Epilepsy;Rats, Inbred Strains;Calcium;Disease Models, Animal;Male;Magnesium;Cerebral Cortex;21 Neurophysiology;Convulsants;24 Pubmed search results 2008;Corpus Callosum;Anticonvulsants}, Medline = {88215605}, Month = {4}, Nlm_Id = {7905558}, Number = {3}, Organization = {Department of Physiology, Royal Veterinary College, London, U.K.}, Pages = {211-24}, Pubmed = {3367658}, Title = {Validation of a neocortical slice preparation for the study of epileptiform activity}, Uuid = {601346DA-E66D-403A-972F-69A954E55EBC}, Volume = {23}, Year = {1988}} @article{Araneda:2002, Abstract = {Dendrodendritic inhibition between mitral and granule cells in the olfactory bulb is thought to play an important role in olfactory discrimination. In this issue of Neuron, explore the propagation of action potentials along the secondary dendrites of mitral cells and their modulation by dendrodendritic inhibition. 0896-6273 Comment Journal Article}, Author = {Araneda, R. C. and Firestein, S. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Neuron}, Keywords = {Olfactory Bulb/physiology;Human;Dendrites/physiology;Synapses/physiology;I pdf;Olfactory Receptor Neurons/physiology;Animals;13 Olfactory bulb anatomy;Action Potentials/*physiology}, Number = {1}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {5-6}, Title = {Action potentials that go the distance}, Uuid = {7310DD25-8DC8-4037-8F53-4A15D6CF23E2}, Volume = {34}, Year = {2002}, url = {papers/Araneda_Neuron2002.pdf}} @article{Araujo:1992, Abstract = {The present study characterizes whether basic fibroblast growth factor (bFGF) is present and released from astroglia, microglia, and hippocampal neurons in vitro. For cell content, bFGF-like immunoreactivity (IR) of cell extracts was measured, whereas release was determined by assessing the levels of bFGF-like IR in media. In addition, the effects of lymphokines and trophic factors that are known to be released from these cells on bFGF release were examined. For all three cell types, bFGF-like IR in extracts of cell lysates was detectable. In addition, media content was highest in astroglial cultures and lowest in neuronal cultures. Although bFGF-like IR of neuronal and microglial media appeared to increase with time in culture, this was likely due to significant astroglial proliferation. Thus, notable levels of bFGF are released by astroglia in vitro. In astroglia, bFGF release was enhanced by interleukin-1 (IL-1), IL-6, and epidermal growth factor (EGF), but not by other lymphokines or NGF. In contrast, bFGF in microglial media was reduced by IL-3, EGF, and NGF, but slightly augmented by gamma-interferon (IFN); other lymphokines were ineffective. In addition, no effects were seen in the neuronal cultures. It is likely that the bFGF found in glial media interacts with bFGF receptors since in both glial and neuronal cell types, a single class of low-capacity (Bmax), high-affinity (Kd) bFGF binding sites was evident. The possibility that endogenous bFGF acts as an autocrine factor for astroglia was further supported by experiments that tested the mitogenic effects of exogenous bFGF on glial cells. bFGF significantly enhanced 3H-thymidine uptake into astroglial, but not microglial, cells in vitro. Thus, the present study demonstrates that a complex regulation of glial bFGF release by astroglia and microglia occurs in vitro. Moreover, the results are consistent with an autocrine role for bFGF in astroglial cultures.}, Author = {Araujo, D. M. and Cotman, C. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Lymphokines;Research Support, Non-U.S. Gov't;Neuroglia;Binding Sites;Alpha;Immunohistochemistry;Nerve Tissue Proteins;Astrocytes;Time Factors;Cell Division;Research Support, U.S. Gov't, P.H.S.;11 Glia;Cells, Cultured;Animals;Fibroblast Growth Factor 2;Nerve Growth Factors;Neurons}, Medline = {92251446}, Month = {5}, Nlm_Id = {8102140}, Number = {5}, Organization = {Department of Psychobiology, University of California, Irvine 92717.}, Pages = {1668-78}, Pubmed = {1578261}, Title = {Basic FGF in astroglial, microglial, and neuronal cultures: characterization of binding sites and modulation of release by lymphokines and trophic factors}, Uuid = {4CA90F3F-3947-447F-BA95-C388B7B97014}, Volume = {12}, Year = {1992}} @article{Araya:2006, Abstract = {In mammalian cortex, most excitatory inputs occur on dendritic spines, avoiding dendritic shafts. Although spines biochemically isolate inputs, nonspiny neurons can also implement biochemical compartmentalization; so, it is possible that spines have an additional function. We have recently shown that the spine neck can filter membrane potentials going into and out of the spine. To investigate the potential function of this electrical filtering, we used two-photon uncaging of glutamate and compared the integration of electrical signals in spines vs. dendritic shafts from basal dendrites of mouse layer 5 pyramidal neurons. Uncaging potentials onto spines summed linearly, whereas potentials on dendritic shafts reduced each other's effect. Linear integration of spines was maintained regardless of the amplitude of the response, distance between spines (as close as < 2 microm), distance of the spines to the soma, dendritic diameter, or spine neck length. Our findings indicate that spines serve as electrical isolators to prevent input interaction, and thus generate a linear arithmetic of excitatory inputs. Linear integration could be an essential feature of cortical and other spine-laden circuits.}, Author = {Araya, Roberto and Eisenthal, Kenneth B. and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {7505876}, Number = {49}, Organization = {Howard Hughes Medical Institute and Departments of Biological Sciences and Chemistry, Columbia University, New York, NY 10027, USA.}, Pages = {18799-804}, Pii = {0609225103}, Pubmed = {17132736}, Title = {Dendritic spines linearize the summation of excitatory potentials}, Uuid = {2BE4898C-6767-414F-BEFF-1668652AF0B3}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0609225103}} @article{Ardid:2007, Abstract = {Selective attention is a fundamental cognitive function that uses top-down signals to orient and prioritize information processing in the brain. Single-cell recordings from behaving monkeys have revealed a number of attention-induced effects on sensory neurons, and have given rise to contrasting viewpoints about the neural underpinning of attentive processing. Moreover, there is evidence that attentional signals originate from the prefrontoparietal working memory network, but precisely how a source area of attention interacts with a sensory system remains unclear. To address these questions, we investigated a biophysically based network model of spiking neurons composed of a reciprocally connected loop of two (sensory and working memory) networks. We found that a wide variety of physiological phenomena induced by selective attention arise naturally in such a system. In particular, our work demonstrates a neural circuit that instantiates the "feature-similarity gain modulation principle," according to which the attentional gain effect on sensory neuronal responses is a graded function of the difference between the attended feature and the preferred feature of the neuron, independent of the stimulus. Furthermore, our model identifies key circuit mechanisms that underlie feature-similarity gain modulation, multiplicative scaling of tuning curve, and biased competition, and provide specific testable predictions. These results offer a synthetic account of the diverse attentional effects, suggesting a canonical neural circuit for feature-based attentional processing in the cortex.}, Author = {Ardid, Salva and Wang, Xiao-Jing J. and Compte, Albert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;Neural Networks (Computer);21 Neurophysiology;Action Potentials;Neocortex;Attention;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {32}, Organization = {Instituto de Neurociencias de Alicante, Universidad Miguel Hern{\'a}ndez-Consejo Superior de Investigaciones Cient{\'\i}ficas, 03550 Sant Joan d'Alacant, Spain.}, Pages = {8486-95}, Pii = {27/32/8486}, Pubmed = {17687026}, Title = {An integrated microcircuit model of attentional processing in the neocortex}, Uuid = {D6195EFE-B1EC-4188-8B8D-FEC2085EFD9C}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1145-07.2007}} @article{Arenkiel:2007, Abstract = {Channelrhodopsin-2 (ChR2) is a light-gated, cation-selective ion channel isolated from the green algae Chlamydomonas reinhardtii. Here, we report the generation of transgenic mice that express a ChR2-YFP fusion protein in the CNS for in vivo activation and mapping of neural circuits. Using focal illumination of the cerebral cortex and olfactory bulb, we demonstrate a highly reproducible, light-dependent activation of neurons and precise control of firing frequency in vivo. To test the feasibility of mapping neural circuits, we exploited the circuitry formed between the olfactory bulb and the piriform cortex in anesthetized mice. In the olfactory bulb, individual mitral cells fired action potentials in response to light, and their firing rate was not influenced by costimulated glomeruli. However, in piriform cortex, the activity of target neurons increased as larger areas of the bulb were illuminated to recruit additional glomeruli. These results support a model of olfactory processing that is dependent upon mitral cell convergence and integration onto cortical cells. More broadly, these findings demonstrate a system for precise manipulation of neural activity in the intact mammalian brain with light and illustrate the use of ChR2 mice in exploring functional connectivity of complex neural circuits in vivo.}, Author = {Arenkiel, Benjamin R. and Peca, Joao and Davison, Ian G. and Feliciano, Catia and Deisseroth, Karl and Augustine, George J. and Ehlers, Michael D. and Feng, Guoping}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {23 Technique; optogenetics; frontiers review}, Month = {4}, Nlm_Id = {8809320}, Number = {2}, Organization = {Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.}, Pages = {205-18}, Pii = {S0896-6273(07)00183-3}, Pubmed = {17442243}, Title = {In vivo light-induced activation of neural circuitry in transgenic mice expressing channelrhodopsin-2}, Uuid = {0C9D8491-68F8-4B2C-88D0-FEC28F6E7A2A}, Volume = {54}, Year = {2007}, url = {papers/Arenkiel_Neuron2007.pdf}, Bdsk-File-2 = {papers/Arenkiel_Neuron2007a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.03.005}} @article{Arlotta:2003, Abstract = {Over most of the past century, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that (i) neurogenesis, the birth of new neurons, is not restricted to embryonic development, but normally also occurs in two limited regions of the adult mammalian brain (the olfactory bulb and the dentate gyrus of the hippocampus); (ii) that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain; and (iii) that it is possible to induce neurogenesis even in regions of the adult mammalian brain, like the neocortex, where it does not normally occur, via manipulation of endogenous multipotent precursors in situ. In the neocortex, recruitment of small numbers of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and newly recruited neurons can form long-distance connections to appropriate targets. This suggests that elucidation of the relevant molecular controls over adult neurogenesis from endogenous neural precursors/stem cells may allow the development of neuronal replacement therapies for neurodegenerative disease and other central nervous system injuries that may not require transplantation of exogenous cells. 0077-8923 Journal Article Review Review, Tutorial}, Author = {Arlotta, P. and Magavi, S. S. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Ann N Y Acad Sci}, Keywords = {01 Adult neurogenesis general;Neurons/*physiology;Nerve Regeneration/*physiology;Environment;Support, U.S. Gov't, Non-P.H.S.;Neocortex/cytology/physiology;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't;Cells, Cultured;A, D, L pdf;Stem Cells/*physiology}, Organization = {MGH-HMS Center for Nervous System Repair, Massachusetts General Hospital, Department of Neurosurgery, Harvard Medical School, Boston, Massachusetts 02114, USA.}, Pages = {229-36}, Title = {Induction of adult neurogenesis: molecular manipulation of neural precursors in situ}, Uuid = {8BA4EEF6-7BF5-41F2-8470-0F20DFB1EF6D}, Volume = {991}, Year = {2003}, url = {papers/Arlotta_AnnNYAcadSci2003.pdf}} @article{Arlotta:2003a, Abstract = {Over the past three decades, research exploring potential neuronal replacement therapies have focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. Over most of the past century of modern neuroscience, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain, and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent findings from our lab demonstrate that it is possible to induce neurogenesis de novo in the adult mammalian brain, particularly in the neocortex where it does not normally occur, and that it may become possible to manipulate endogenous multipotent precursors in situ to replace lost or damaged neurons. Recruitment of new neurons can be induced in a region-specific, layer-specific, and neuronal type-specific manner, and newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that do not require transplantation of exogenous cells. 0531-5565 Journal Article Review Review, Academic}, Author = {Arlotta, P. and Magavi, S. S. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Exp Gerontol}, Keywords = {Neurons/*physiology;Olfactory Bulb/physiology;Human;A, D, L pdf;Animals;Neocortex/physiology;*Stem Cell Transplantation;17 Transplant Regeneration;01 Adult neurogenesis general;Mammals/*physiology;Support, Non-U.S. Gov't;06 Adult neurogenesis injury induced;Hippocampus/physiology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Neurodegenerative Diseases/therapy;*Nerve Regeneration;Mice}, Number = {1-2}, Organization = {Division of Neuroscience, Department of Neurology and Program in Neuroscience, Children's Hospital, Harvard Medical School, 320 Longwood Ave., Enders 354, Boston, MA 02115, USA.}, Pages = {173-82}, Title = {Molecular manipulation of neural precursors in situ: induction of adult cortical neurogenesis}, Uuid = {178943B5-72A5-4B5F-86E6-84AF071A0E26}, Volume = {38}, Year = {2003}, url = {papers/Arlotta_ExpGerontol2003}} @article{Arlotta:2005, Abstract = {Within the vertebrate nervous system, the presence of many different lineages of neurons and glia complicates the molecular characterization of single neuronal populations. In order to elucidate molecular mechanisms underlying the specification and development of corticospinal motor neurons (CSMN), we purified CSMN at distinct stages of development in vivo and compared their gene expression to two other pure populations of cortical projection neurons: callosal projection neurons and corticotectal projection neurons. We found genes that are potentially instructive for CSMN development, as well as genes that are excluded from CSMN and are restricted to other populations of neurons, even within the same cortical layer. Loss-of-function experiments in null mutant mice for Ctip2 (also known as Bcl11b), one of the newly characterized genes, demonstrate that it plays a critical role in the development of CSMN axonal projections to the spinal cord in vivo, confirming that we identified central genetic determinants of the CSMN population.}, Author = {Arlotta, Paola and Molyneaux, Bradley J. and Chen, Jinhui and Inoue, Jun and Kominami, Ryo and Macklis, Jeffrey D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Cell Differentiation;Animals;Transcription Factors;Gene Expression Regulation, Developmental;Oligonucleotide Array Sequence Analysis;ras Proteins;Mice, Inbred C57BL;Nerve Growth Factors;Motor Cortex;Pyramidal Tracts;Gene Expression Profiling;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Mice, Knockout;Superior Colliculus;Motor Neurons;Mice;24 Pubmed search results 2008;Growth Cones;Corpus Callosum;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {8809320}, Number = {2}, Organization = {MGH-HMS Center for Nervous System Repair, Departments of Neurosurgery and Neurology, Program in Neuroscience and Harvard Stem Cell Institute, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.}, Pages = {207-21}, Pii = {S0896627304008530}, Pubmed = {15664173}, Title = {Neuronal subtype-specific genes that control corticospinal motor neuron development in vivo}, Uuid = {C85FDC18-DF78-46F9-A3AC-B7D8285ECE75}, Volume = {45}, Year = {2005}, url = {papers/Arlotta_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.12.036}} @article{Armentano:2006, Abstract = {The transcription factor COUP-TFI (NR2F1), an orphan member of the nuclear receptor superfamily, is an important regulator of neurogenesis, cellular differentiation and cell migration. In the forebrain, COUP-TFI controls the connectivity between thalamus and cortex and neuronal tangential migration in the basal telencephalon. Here, we show that COUP-TFI is required for proper axonal growth and guidance of all major forebrain commissures. Fibres of the corpus callosum, the hippocampal commissure and the anterior commissure project aberrantly and fail to cross the midline in COUP-TFI null mutants. Moreover, hippocampal neurons lacking COUP-TFI have a defect in neurite outgrowth and show an abnormal axonal morphology. To search for downstream effectors, we used microarray analysis and showed that, in the absence of COUP-TFI, expression of various cytoskeleton molecules involved in neuronal morphogenesis is affected. Diminished protein levels of the microtubule-associated protein MAP1B and increased levels of the GTP-binding protein RND2 were confirmed in the developing cortex in vivo and in primary hippocampal neurons in vitro. Therefore, based on morphological studies, gene expression profiling and primary cultured neurons, the present data uncover a previously unappreciated intrinsic role for COUP-TFI in axonal growth in vivo and supply one of the premises for COUP-TFI coordination of neuronal morphogenesis in the developing forebrain.}, Author = {Armentano, Maria and Filosa, Alessandro and Andolfi, Gennaro and Studer, Mich\`{e}le}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8701744}, Number = {21}, Organization = {TIGEM (Telethon Institute of Genetics and Medicine Disorders Program, Via P. Castellino 111, 80131 Napoli, Italy.}, Pages = {4151-62}, Pii = {dev.02600}, Pubmed = {17021036}, Title = {COUP-TFI is required for the formation of commissural projections in the forebrain by regulating axonal growth}, Uuid = {73485913-8D33-4F60-8113-1D702EAEA8F4}, Volume = {133}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.02600}} @article{Arnhold:2000, Abstract = {OBJECT: The aim of this investigation was to assess new information concerning the capacity of transplanted embryonic stem cell (ESC)-derived neuronal cells to migrate into host brain and to evaluate these cells as a possible source for cell replacement therapy in neurodegenerative disorders such as Parkinson's disease (PD). METHODS: The authors investigated the ability of ESC-derived neural precursor cells to migrate and differentiate in a host striatum by using a D3-derived ESC clone that was transfected stably with a chicken beta-actin cytomegalovirus enhancer-driven green fluorescent protein (GFP)-labeled construct. This procedure allowed easy monitoring of all transplanted cells because of the green fluorescent labeling of donor cells. This approach also afforded easy estimation of cell integration and simultaneous observation of the entire transplanted cell population in relation to immunocytochemically identified neuronal and glial differentiation. After selection of nestin-positive neural precursor cells in a synthetic medium, they were implanted into the striatum of male adult Wistar rats. Their integration was analyzed on morphological studies performed 3 days to 4 weeks posttransplantation. CONCLUSIONS: The investigators found that after transplantation, a subpopulation of GFP-labeled cells differentiated into various neural morphological types that were positive for the mouse-specific Thy-1 antigen, which is known be expressed on neurons, as well as being positive for the astroglial marker glial fibrillary acidic protein. Moreover, GFP-expressing cells that were negative for either of these markers remained close to the injection site, presumably representing other derivatives of the neural lineage. Together, these findings contribute to basic research regarding future transplantation strategies in neurodegenerative diseases such as PD.}, Author = {Arnhold, S. and Lenartz, D. and Kruttwig, K. and Klinz, F. J. and Kolossov, E. and Hescheler, J. and Sturm, V. and Andressen, C. and Addicks, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0022-3085}, Journal = {J Neurosurg}, Keywords = {Cell Differentiation;Animals;Stem Cell Transplantation;Corpus Striatum;Humans;Rats;Cell Movement;Parkinson Disease;Antigens, Thy-1;11 Glia;Rats, Wistar;Male;Green Fluorescent Proteins;Fetal Tissue Transplantation;Neurons;Neuroglia;Luminescent Proteins;Stem Cells;Chickens}, Medline = {21003934}, Month = {12}, Nlm_Id = {0253357}, Number = {6}, Organization = {Institute of Anatomy I, Department of Stereotactic and Functional Neurosurgery, University of Cologne, Germany. stefan.arnhold\@uni-koeln.de}, Pages = {1026-32}, Pubmed = {11117845}, Title = {Differentiation of green fluorescent protein-labeled embryonic stem cell-derived neural precursor cells into Thy-1-positive neurons and glia after transplantation into adult rat striatum}, Uuid = {04EC7C34-C5F7-4323-8718-B0D85E8763C7}, Volume = {93}, Year = {2000}} @article{Arnold:1991, Abstract = {The cytoarchitecture of the entorhinal cortex was examined in the brains of six patients with a diagnosis of schizophrenia and in 16 controls. All six brains of schizophrenic patients showed abnormalities of the rostral and intermediate portions of the entorhinal cortex. The abnormalities included aberrant invaginations of the surface, disruption of cortical layers, heterotopic displacement of neurons, and paucity of neurons in superficial layers. These changes suggest disturbed development. Because the entorhinal cortex is pivotal for neural systems that mediate corticohippocampal interactions, early disruption of its structure could lead to important neuropsychological changes during development and in adult life and could contribute to the symptomatology of schizophrenia.}, Author = {Arnold, S. E. and Hyman, B. T. and Van Hoesen, G. W. and Damasio, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0003-990X}, Journal = {Arch Gen Psychiatry}, Keywords = {10 Development;Humans;Middle Aged;Neural Pathways;Psychosurgery;Schizophrenia;Female;Cell Count;Hippocampus;Male;Aged;10 genetics malformation;Neurons;research support, u.s. gov't, p.h.s.;Adult;Cerebral Cortex;Temporal Lobe;24 Pubmed search results 2008;Limbic System}, Month = {7}, Nlm_Id = {0372435}, Number = {7}, Organization = {Department of Neurology, University of Iowa College of Medicine, Iowa City.}, Pages = {625-32}, Pubmed = {2069493}, Title = {Some cytoarchitectural abnormalities of the entorhinal cortex in schizophrenia}, Uuid = {CDDF4F64-6CD2-4A5B-9075-2AC17A5E179A}, Volume = {48}, Year = {1991}} @article{Aronica:2005, Abstract = {Cells of the microglia/macrophage lineage represent an important component of different brain tumours. However, there is little information about the microglia/macrophage cell system in glioneuronal tumours and its possible contribution to the high epileptogenecity of these lesions. In the present study, the distribution of cells of the microglia/macrophage lineage was studied by immunocytochemistry for CD68 and human leucocyte antigen (HLA)-DR in a group of glioneuronal tumours, including gangliogliomas (GG, n = 30), and dysembryoplastic neuroepithelial tumours (DNT, n = 17), from patients with chronic intractable epilepsy. A significant number of microglia/macrophage cells were observed in the large majority of glioneuronal tumours, both within the tumour and in the peritumoral region. Activated microglial cells positive for HLA-DR were localized around blood vessels and clustered around tumour neuronal cells. The density of activated microglial cells correlated with the duration of epilepsy, as well as with the frequency of seizures prior to surgical resection. These observations indicate that the presence of cells of the microglial/macrophage cell system is a feature of glioneuronal tumours and is functionally related to epilepsy, either directly in epileptogenesis or through activation following seizure activity.}, Author = {Aronica, E. and Gorter, J. A. and Redeker, S. and Ramkema, M. and Spliet, W. G. M. and van Rijen, P. C. and Leenstra, S. and Troost, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Epilepsy;Adult;Adolescent;Female;Immunohistochemistry;HLA-DR Antigens;Middle Aged;Microglia;Child, Preschool;Child;11 Glia;Humans;Neoplasms, Neuroepithelial;Brain;Male}, Month = {6}, Nlm_Id = {7609829}, Number = {3}, Organization = {Department of (Neuro)Pathology, Academic Medical Centre, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands. e.aronica\@amc.uva.nl}, Pages = {280-91}, Pii = {NAN636}, Pubmed = {15885065}, Title = {Distribution, characterization and clinical significance of microglia in glioneuronal tumours from patients with chronic intractable epilepsy}, Uuid = {5FCDA117-D840-47C5-96A1-59872617A7E1}, Volume = {31}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1365-2990.2004.00636.x}} @article{Aronov:2003, Abstract = {Spike train metrics quantify the notion of dissimilarity, or distance, between spike trains and between multineuronal responses (J. Neurophysiol. 76 (1996) 1310, Network 8 (1997) 127). We present a new algorithm for the implementation of a metric based on the timing of individual spikes and on their neurons of origin. This algorithm surpasses the earlier approach in speed by a factor that grows exponentially with the number of neurons, substantially extending the applicability of metric space methods to the study of coding in larger neuronal populations.}, Author = {Aronov, Dmitriy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {23 Technique;21 Neurophysiology;Action Potentials;Algorithms;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008;Neurons;Metric System}, Month = {4}, Nlm_Id = {7905558}, Number = {2}, Organization = {Department of Biological Sciences, Columbia University, 1002 Fairchild, Mail Code 2436, 1212 Amsterdam Avenue, New York, NY 10027, USA. da2006\@columbia.edu}, Pages = {175-9}, Pii = {S0165027003000062}, Pubmed = {12706847}, Title = {Fast algorithm for the metric-space analysis of simultaneous responses of multiple single neurons}, Uuid = {3FC6C3B1-EBBD-46BC-9DB7-5F5BCA9DA718}, Volume = {124}, Year = {2003}, url = {papers/Aronov_JNeurosciMethods2003.pdf}} @article{Arsenijevic:1998, Abstract = {Insulin-like growth factor-I (IGF-I) has been reported previously to promote the proliferation, survival, and maturation of sympathetic neuroblasts, the genesis of retinal neurons, and the survival of CNS projection and motor neurons. Here we asked whether IGF-I could promote the in vitro differentiation of postmitotic mammalian CNS neuronal precursors derived from multipotent epidermal growth factor (EGF)-responsive stem cells. In the absence of IGF-I, virtually no neurons were present in cultured stem cell progeny, whereas IGF-I increased neuron number by eight- to 40-fold. Brief exposures (2 hr) to IGF-I were sufficient to allow for neuronal differentiation without affecting proliferation or survival. IGF-I actions could be mimicked by insulin and IGF-II at concentrations that correspond to the pharmacology of the IGF-I receptor, the latter for which the mRNA was detected in undifferentiated stem cell progeny. Although ineffectual alone at low concentrations (10 nM) that would activate its own receptor, insulin was able to potentiate the actions of IGF-I by acting on mitotically active neural precursors. When neuronal precursor differentiation by IGF-I was examined in relation to brain-derived neurotrophic factor (BDNF), two important observations were made: (1) BDNF could potentiate the differentiating actions of IGF-I plus insulin, and (2) BDNF could act on a separate population of precursors that did not require IGF-I plus insulin for differentiation. Taken together, these results suggest that IGF-I and BDNF may act together or sequentially to promote neuronal precursor differentiation. 0270-6474 Journal Article Review Review, Tutorial}, Author = {Arsenijevic, Y. and Weiss, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Neurosci}, Keywords = {C abstr;Stem Cells/*cytology/drug effects/*physiology;Brain/cytology/*physiology;Insulin-Like Growth Factor I/metabolism/pharmacology/*physiology;Mitosis/*physiology;Brain-Derived Neurotrophic Factor/pharmacology/physiology;Neurons/cytology/*physiology;Drug Synergism;Mice/embryology;Cell Differentiation/physiology;04 Adult neurogenesis factors;Insulin/pharmacology;Support, Non-U.S. Gov't;Animals;Cell Count/drug effects;Receptors, Somatomedin/physiology}, Number = {6}, Organization = {Department of Anatomy, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada T2N4N1.}, Pages = {2118-28}, Pubmed = {9482798}, Title = {Insulin-like growth factor-I is a differentiation factor for postmitotic CNS stem cell-derived neuronal precursors: distinct actions from those of brain-derived neurotrophic factor}, Uuid = {F1D595A9-86B1-4D8E-A311-73B9AF5D807A}, Volume = {18}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9482798}} @article{Arsiero:2007, Abstract = {The role of irregular cortical firing in neuronal computation is still debated, and it is unclear how signals carried by fluctuating synaptic potentials are decoded by downstream neurons. We examined in vitro frequency versus current (f-I) relationships of layer 5 (L5) pyramidal cells of the rat medial prefrontal cortex (mPFC) using fluctuating stimuli. Studies in the somatosensory cortex show that L5 neurons become insensitive to input fluctuations as input mean increases and that their f-I response becomes linear. In contrast, our results show that mPFC L5 pyramidal neurons retain an increased sensitivity to input fluctuations, whereas their sensitivity to the input mean diminishes to near zero. This implies that the discharge properties of L5 mPFC neurons are well suited to encode input fluctuations rather than input mean in their firing rates, with important consequences for information processing and stability of persistent activity at the network level.}, Author = {Arsiero, Maura and L{\"u}scher, Hans-Rudolf R. and Lundstrom, Brian Nils and Giugliano, Michele}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Electric Stimulation;research support, non-u.s. gov't;21 Neurophysiology;Action Potentials;Prefrontal Cortex;Rats;Rats, Wistar;21 Circuit structure-function;comparative study;research support, n.i.h., extramural;Nerve Net;Animals;24 Pubmed search results 2008;Neurons}, Month = {3}, Nlm_Id = {8102140}, Number = {12}, Organization = {Institute of Physiology, University of Bern, CH-3012 Bern, Switzerland.}, Pages = {3274-84}, Pii = {27/12/3274}, Pubmed = {17376988}, Title = {The impact of input fluctuations on the frequency-current relationships of layer 5 pyramidal neurons in the rat medial prefrontal cortex}, Uuid = {F52D59ED-541F-4EF1-A327-D1AA953A106E}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4937-06.2007}} @article{Arvidsson:2001, Abstract = {Neurogenesis in the adult rat dentate gyrus was studied following focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Animals were subjected to either 30 min of MCAO, which causes damage confined to the striatum, or 2 h of MCAO, which leads to both striatal and cortical infarction. When compared to sham-operated rats, MCAO-rats showed a marked increase of the number of cells double-labelled for 5- bromo-2'-deoxyuridine-5'-monophosphate (BrdU; injected during 4-6 days postischemia) and neuronal-specific antigen (NeuN; a marker of postmitotic neurons) in the ipsilateral dentate granule cell layer and subgranular zone at 5 weeks following the 2 h insult. Only a modest and variable increase of BrdU-labelled cells was found after 30 min of MCAO. The enhanced neurogenesis was not dependent on cell death in the hippocampus, and its magnitude was not correlated to the degree of cortical damage. Systemic administration of the N-methyl-D-aspartate (NMDA) receptor blocker dizocilpine maleate (MK-801) completely suppressed the elevated neurogenesis following 2 h of MCAO. Our findings indicate that stroke leads to increased neurogenesis in the adult rat dentate gyrus through glutamatergic mechanisms acting on NMDA receptors. This modulatory effect may be mediated through changes in the levels of several growth factors, which occur after stroke, and could influence various regulatory steps of neurogenesis.}, Author = {Arvidsson, A. and Kokaia, Z. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:39:25 -0400}, Journal = {Eur J Neurosci}, Keywords = {Recovery of Function/drug effects/physiology;Rats;Excitatory Amino Acid Antagonists/pharmacology;Receptors, N-Methyl-D-Aspartate/antagonists &inhibitors/*metabolism;D both;Infarction, Middle Cerebral Artery/*metabolism/pathology/physiopathology;Animal;Dentate Gyrus/cytology/*growth &development/metabolism;Cell Differentiation/drug effects/*physiology;Rats, Wistar;Male;Support, Non-U.S. Gov't;Neuronal Plasticity/drug effects/*physiology;Cell Division/drug effects/*physiology;Neurons/cytology/drug effects/*metabolism;06 Adult neurogenesis injury induced;Brain Ischemia/metabolism/pathology/physiopathology;Immunohistochemistry;Bromodeoxyuridine/pharmacokinetics;Biological Markers/analysis;Antimetabolites/pharmacokinetics}, Number = {1}, Organization = {Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11, University Hospital, SE-221 84, Lund, Sweden. andrea.arvidsson\@neurol.lu.se}, Pages = {10-8.}, Title = {N-methyl-D-aspartate receptor-mediated increase of neurogenesis in adult rat dentate gyrus following stroke}, Uuid = {9730EB66-EC81-11DA-8605-000D9346EC2A}, Volume = {14}, Year = {2001}, url = {papers/Arvidsson_EurJNeurosci2001.pdf}} @article{Arvidsson:2002, Abstract = {In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans. 1078-8956 Journal Article}, Author = {Arvidsson, A. and Collin, T. and Kirik, D. and Kokaia, Z. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:27:23 -0400}, Journal = {Nat Med}, Keywords = {Animals;Cerebrovascular Accident/metabolism/*pathology;Rats;Brain/*pathology;Neurons/metabolism/*pathology;D pdf;Cell Movement;Stem Cells/cytology;Rats, Wistar;Male;DNA-Binding Proteins/metabolism;Homeodomain Proteins/metabolism;Support, Non-U.S. Gov't;Neuropeptides/metabolism;Lateral Ventricles/pathology;Cell Division;Proto-Oncogene Proteins/metabolism;Biological Markers/analysis}, Number = {9}, Organization = {Section of Restorative Neurology, Wallenberg Neuroscience Center, Lund University Hospital, Lund, Sweden. andreas.arvidsson\@neurol.lu.se}, Pages = {963-70}, Title = {Neuronal replacement from endogenous precursors in the adult brain after stroke}, Uuid = {BAA16CF7-C26D-11DA-969D-000D9346EC2A}, Volume = {8}, Year = {2002}, url = {../Data/Papers/text/dissertation/dissertation.pdf}} @article{Arvidsson:2001a, Abstract = {Gene expression for glial cell line-derived neurotrophic factor (GDNF) family ligands and receptors was analyzed with in situ hybridization after two focal ischemic insults of different severities. Focal ischemia was induced in rats by either 30 min or 2 h of middle cerebral artery occlusion (MCAO), causing damage to the striatum only, or involving also the parietal cortex, respectively. We found modest, transient elevation of GDNF mRNA in the dentate granule cell layer. In addition, the number of GDNF mRNA-expressing cells increased in the cortex and striatum after 2 h or 30 min of MCAO, respectively. No changes of neurturin or persephin mRNA expression were detected. Both c- Ret and GFRalpha1 mRNA levels were markedly increased in the ipsilateral cortex outside the ischemic lesion at 6-24 h after the 2-h insult, whereas GFRalpha2 expression was decreased in cortical areas both within and outside the lesion. Similar increases of c-Ret and GFRalpha1 mRNA levels were detected in the striatum, and to a lesser extent, in the cortex following 30 min of MCAO. The 2-h insult also gave rise to transient increases of c-Ret and GFRalpha1 mRNA in hippocampal subregions. Thirty minutes and 2 h of MCAO lead to elevated c-Ret, and GFRalpha1 or GFRalpha2 mRNA expression, respectively, in the ipsilateral ventroposterolateral thalamic nucleus. Both insults induced increased levels of GFRalpha1 mRNA in the subventricular zone of the lateral ventricle.Our data indicate major changes of GDNF family signaling in the forebrain, regulated mainly through altered receptor levels, in the post-ischemic phase. These changes could enhance neuroprotective and neuroregenerative responses both to endogenous and exogenous GDNF ligands. Using Smart Source Parsing}, Author = {Arvidsson, A. and Kokaia, Z. and Airaksinen, M. S. and Saarma, M. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Neuroscience}, Keywords = {D abstr;06 Adult neurogenesis injury induced}, Number = {1}, Pages = {27-41}, Title = {Stroke induces widespread changes of gene expression for glial cell line-derived neurotrophic factor family receptors in the adult rat brain}, Uuid = {7BA2B945-00E6-4C0B-829F-33DFF84AFE9F}, Volume = {106}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11564414}} @article{Asano:2001, Abstract = {G proteins play important roles in transmembrane signal transduction, and various isoforms of each subunit, alpha, beta and gamma, are highly expressed in the brain. The Ggamma5 subunit is a minor isoform in the adult brain, but we have previously shown it to be highly expressed in the proliferative region of the ventricular zone in the rat embryonic brain. We show here that Ggamma5 is also selectively localized in a proliferative region in the adult rat brain, including the subventricular zone of the lateral ventricle and rostral migratory stream. The Galphai2 subunit colocalized with Ggamma5 in these regions, the two subunits being present in neuronal precursors and ependymal cells but not in proliferating astrocytes. In addition, intense staining of Ggamma5 was seen in axons of the olfactory neurons, which are known to regenerate. These results suggest specific roles for Ggamma5 in precursor cells during neurogenesis so that this isoform might be a useful biological marker.}, Author = {Asano, T. and Shinohara, H. and Morishita, R. and Ueda, H. and Kawamura, N. and Katoh-Semba, R. and Kishikawa, M. and Kato, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Neurochem}, Keywords = {Lateral Ventricles/*chemistry/cytology/embryology/growth &development;Axons/chemistry;Cell Differentiation;Protein Subunits;Olfactory Bulb/*chemistry/cytology/embryology/growth &development;Rats;Immunoenzyme Techniques;Heterotrimeric GTP-Binding Proteins/*analysis;Cell Movement;Animal;C abstr;Rats, Wistar;Male;Protein Isoforms/*analysis;Support, Non-U.S. Gov't;Interneurons/*chemistry/cytology;Cell Lineage;Stem Cells/*chemistry/cytology;04 Adult neurogenesis factors;Ependyma/*chemistry/cytology;Bromodeoxyuridine/diagnostic use;Gestational Age;Nerve Tissue Proteins/*analysis}, Number = {6}, Organization = {Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan. tosano\@inst-hsc.pref.aichi.jp}, Pages = {1129-35.}, Title = {Selective localization of G protein gamma5 subunit in the subventricular zone of the lateral ventricle and rostral migratory stream of the adult rat brain}, Uuid = {607EA09B-2541-41A7-B561-DD05B228E753}, Volume = {79}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11752054%20http://www.jneurochem.org/cgi/content/full/79/6/1129%20http://www.jneurochem.org/cgi/content/abstract/79/6/1129}} @book{Asanuma:1989, Abstract = {88043160 Hiroshi Asanuma. ill. ; 24 cm .}, Author = {Asanuma, Hiroshi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Isbn = {0881675415}, Keywords = {M QP383.15 .A83 1989 599/.018;Motor cortex Physiology.}, Publisher = {Raven Press}, Title = {The motor cortex}, Uuid = {FF91280D-951C-4828-82FF-F4D719F65D32}, Year = {1989}} @article{Aschner:1999, Abstract = {Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in a layer of connective tissue. The term, or its shortened form--glia, has persisted as the preferred generic term for these cells. A reciprocal relationship exists between neurons and glia, and this association is vital for mutual differentiation, development, and functioning of these cell types. Therefore, perturbations in glial cell function, as well as glial metabolism of chemicals to active intermediates, can lead to neuronal dysfunction. The purpose of this review is to explore neuroglial sites of neurotoxicant actions, discuss potential mechanisms of glial-induced or glial-mediated central nervous system and peripheral nervous system damage, and review the role of glial cells in neurotoxicity development.}, Author = {Aschner, M. and Allen, J. W. and Kimelberg, H. K. and LoPachin, R. M. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0362-1642}, Journal = {Annu Rev Pharmacol Toxicol}, Keywords = {Neuroglia;review, academic;Schwann Cells;Human;Not relevant;11 Glia;Support, U.S. Gov't, P.H.S.;Animals;Nervous System Diseases;review}, Medline = {99261465}, Nlm_Id = {7607088}, Organization = {Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. maschner\@bgsm.edu}, Pages = {151-73}, Pubmed = {10331080}, Title = {Glial cells in neurotoxicity development}, Uuid = {E718C1D3-9FA7-4271-BD98-E5F97055D5B8}, Volume = {39}, Year = {1999}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.pharmtox.39.1.151}} @article{Asensio:2001, Abstract = {The CXC chemokine gamma interferon (IFN-gamma)-inducible protein CXCL10/IP-10 is markedly elevated in cerebrospinal fluid and brain of individuals infected with human immunodeficiency virus type 1 (HIV-1) and is implicated in the pathogenesis of HIV-associated dementia (HAD). To explore the possible role of CXCL10/IP-10 in HAD, we examined the expression of this and other chemokines in the central nervous system (CNS) of transgenic mice with astrocyte-targeted expression of HIV gp120 under the control of the glial fibrillary acidic protein (GFAP) promoter, a murine model for HIV-1 encephalopathy. Compared with wild-type controls, CNS expression of the CC chemokine gene CCL2/MCP-1 and the CXC chemokine genes CXCL10/IP-10 and CXCL9/Mig was induced in the GFAP-HIV gp120 mice. CXCL10/IP-10 RNA expression was increased most and overlapped the expression of the transgene-encoded HIV gp120 gene. Astrocytes and to a lesser extent microglia were identified as the major cellular sites for CXCL10/IP-10 gene expression. There was no detectable expression of any class of IFN or their responsive genes. In astrocyte cultures, soluble recombinant HIV gp120 protein was capable of directly inducing CXCL10/IP-10 gene expression a process that was independent of STAT1. These findings highlight a novel IFN- and STAT1-independent mechanism for the regulation of CXCL10/IP-10 expression and directly link expression of HIV gp120 to the induction of CXCL10/IP-10 that is found in HIV infection of the CNS. Finally, one function of IP-10 expression may be the recruitment of leukocytes to the CNS, since the brain of GFAP-HIV gp120 mice had increased numbers of CD3(+) T cells that were found in close proximity to sites of CXCL10/IP-10 RNA expression.}, Author = {Asensio, V. C. and Maier, J. and Milner, R. and Boztug, K. and Kincaid, C. and Moulard, M. and Phillipson, C. and Lindsley, K. and Krucker, T. and Fox, H. S. and Campbell, I. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {T-Lymphocytes;Animals;HIV-1;DNA-Binding Proteins;Trans-Activators;Astrocytes;Humans;Solubility;Cells, Cultured;Brain;Interferon Type II;Mice, Transgenic;Mice, Inbred C57BL;Recombinant Fusion Proteins;11 Glia;Research Support, U.S. Gov't, P.H.S.;Receptors, Chemokine;Chemokines, CXC;Interferon-alpha;Mice;Gene Expression;HIV Envelope Protein gp120;Glial Fibrillary Acidic Protein}, Medline = {21329489}, Month = {8}, Nlm_Id = {0113724}, Number = {15}, Organization = {Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.}, Pages = {7067-77}, Pubmed = {11435587}, Title = {Interferon-independent, human immunodeficiency virus type 1 gp120-mediated induction of CXCL10/IP-10 gene expression by astrocytes in vivo and in vitro}, Uuid = {2BDE957A-8584-4926-AF47-97B9A1B28190}, Volume = {75}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.75.15.7067-7077.2001}} @article{Asheuer:2004, Abstract = {In rodents, bone marrow-derived cells enter the brain during adult life. Allogeneic bone marrow transplantation is used to treat genetic CNS diseases, but the fate of human bone marrow and CD34(+) cells within the brain remains to be elucidated. The present study demonstrates that cells derived from human CD34(+) cells, isolated from either cord blood or peripheral blood, migrate into the brain after infusion into nonobese diabetic/severe combined immunodeficient mice. Both types of CD34(+)-derived cells differentiate into perivascular and ramified microglia. The lentiviral transfer of genes into CD34(+) cells before infusion does not modify the differentiation of human CD34(+) cells into microglia, allowing new transgenic proteins to be expressed in these cells. The transplantation of CD34(+) cells could thus be used for the treatment of CNS diseases.}, Author = {Asheuer, Muriel and Pflumio, Fran\c{c}oise and Benhamida, Sonia and Dubart-Kupperschmitt, Anne and Fouquet, Fran\c{c}oise and Imai, Yoshinori and Aubourg, Patrick and Cartier, Nathalie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Differentiation;Mice, Inbred NOD;Animals;Humans;Central Nervous System Diseases;Transplantation, Heterologous;Recombinant Proteins;Microglia;Brain;Mice, SCID;Antigens, CD34;11 Glia;Green Fluorescent Proteins;Hematopoietic Stem Cell Transplantation;Fatty Acids;Peripheral Blood Stem Cell Transplantation;Hematopoietic Stem Cells;Infant, Newborn;Mice;Fetal Blood;Luminescent Proteins;Gene Expression;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {7505876}, Number = {10}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U561, H\^{o}pital Saint-Vincent de Paul, 75014 Paris, France.}, Pages = {3557-62}, Pii = {0306431101}, Pubmed = {14990803}, Title = {Human CD34+ cells differentiate into microglia and express recombinant therapeutic protein}, Uuid = {0F3ED2E5-544E-4AEB-97B1-16B50A443B3E}, Volume = {101}, Year = {2004}, url = {papers/Asheuer_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0306431101}} @article{Ashwell:1990, Abstract = {The appearance and distribution of microglia in the developing cerebellum has been examined with the aid of a peroxidase-conjugated lectin derived from Griffonia simplicifolia. This distribution has in turn been correlated with that of pyknotic figures in the same Nissl-counterstained sections, in order to gain an understanding of the role of microglial in the developing cerebellum. Round and ameboid microglia may be recognised in the fetal cerebellum as early as E11. Numbers of microglia increase steadily from that time, with initial concentrations in the region of the dorsal and ventricular surfaces. By P1, concentrations of both pyknotic figures and ameboid microglia begin to appear in the region of the future cerebellar medulla. Ameboid microglia are recognisable in the cerebellar medulla until P10, with particular concentrations where folia branch and in the rostral cerebellar peduncles. After this time only resting microglia are found in the cerebellum. Concentrations of microglia largely match the positions of pyknotic figures throughout development, except at P10 and P14, when cell death is found in the external granular layer without an accompanying concentration of microglia. Electron microscopic examination of the phagosomes of ameboid microglia at P5 and P6 indicates that these cells are mainly concerned with the phagocytosis of entire cells rather than axons. Cell death in the cerebellar medulla may serve to clear pathways for developing cortical afferents and efferents, or to increase the mechanical plasticity of the medulla during cortical folding.}, Author = {Ashwell, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Connective Tissue Cells;Lectins;Microscopy, Electron;Not relevant;Cell Survival;Cerebellum;11 Glia;Mice;Animals;Phagocytosis}, Medline = {91070714}, Month = {9}, Nlm_Id = {8908639}, Number = {2}, Organization = {School of Anatomy, University of NSW, Kensington, Australia.}, Pages = {219-30}, Pubmed = {2253324}, Title = {Microglia and cell death in the developing mouse cerebellum}, Uuid = {4A35B912-869C-4437-A987-D6D129D28A2A}, Volume = {55}, Year = {1990}} @article{Ashwell:1989, Abstract = {In this study the development of ameboid microglia and resting microglia in the retina of the albino rabbit has been examined by means of a lectin derived from Griffonia simplicifolia. Ameboid microglia are present in the retina as early as E12, when the optic fissure is in the process of closure, and appear to be concentrated initially at the vitreal surface. At E14 many ameboid microglia can be seen to extend processes to the ventricular surface of the cytoblast layer, but in subsequent ages these cells are rare and ameboid microglia are largely confined to the ganglion cell layer, inner plexiform layer, and occasionally the developing inner nuclear layer. By adult life, mature (or resting) microglia are confined to the inner plexiform and ganglion cell layers. Numbers of microglia increase steadily throughout fetal life from a mean of 400 at E14, the earliest age quantified, to a peak of 28,600 at E30. There is a small postnatal drop in numbers to 17,150 at P9. Microglia could only be labelled faintly in animals older than P11, but analysis of two adult (P130) retinas with adequate labelling suggested that numbers rise to a value of about 23,800 at this age. Ameboid microglia thus appear in the retina 11 days prior to the onset of axon loss in the optic nerve (about E23) and 14 days prior to the beginning of the period of reduction of retinal ganglion cell numbers (about E26). The present findings indicate that while some microglial precursors may enter the retina in response to debris generated during the natural retinal ganglion cell death period, most enter the retina well before this period. Also, microglia present a uniform density distribution with apparently regular spacing as early as E16, so the uniform regular distribution cannot simply be the consequence of regularly distributed pyknotic figures as previously suggested.}, Author = {Ashwell, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Retina;Neuroglia;Female;Not relevant;Cell Division;Cell Survival;Retinal Vessels;11 Glia;Immunoenzyme Techniques;Retinal Ganglion Cells;Animals;Horseradish Peroxidase;Phagocytosis;Rabbits;Male}, Medline = {89380914}, Month = {9}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Anatomy, University of Sydney, NSW, Australia.}, Pages = {286-301}, Pubmed = {2674209}, Title = {Development of microglia in the albino rabbit retina}, Uuid = {F90A0688-8CFB-4008-BC71-6875EE003036}, Volume = {287}, Year = {1989}} @article{Ashwell:1989a, Abstract = {We have examined the development of microglia in the rat retina, using a peroxidase-conjugated lectin derived from Griffonia simplicifolia. Retinas were studied from animals aged from E(embryonic day)12, just after the invagination of the optic cup and prior to the closure of the optic fissure, to adulthood. The lectin also proved a sensitive label for the endothelial cells of the developing retina. Our results provide some support for the view that microglia are derived from the monocyte-macrophage series of blood cells. At E12, most labeled cells were found at the vitreal surface, suggesting that they had come from the hyaloid circulation, while some had entered the retina and appeared to be migrating towards its ventricular surface. From E14 to early postnatal ages, most labeled cells had processes and resembled the amoeboid microglial cells described in silver carbonate staining studies (Ling, 1982). The number of labeled cells rose from about 700 to E14 to a peak of about 27,000 at P(postnatal day)7, and fell to about 19,600 by P12. As early as E16, a regularity was apparent in the distribution of microglial cells over the surface of the retina, the cells tending to avoid each other. Microglial cells are found throughout the thickness of the very young retina, but as the layers of the retina differentiate, they are increasingly restricted to the inner half of the retina. Our findings indicate that microglia enter the retina well before the period of neuronal death, making it unlikely that they invade the retina solely in response to cell death. Our results confirm however that, once in the retina, microglia become associated with, and appear to phagocytose, the pyknotic debris which appears during the period of neuronal death. They also become closely associated with the retinal vasculature. In the adult, the intensity of the labeling of microglia was much reduced. Those cells which were labeled appeared more differentiated, resembling the "resting microglia" described in earlier studies.}, Author = {Ashwell, K. W. and Holl{\"a}nder, H. and Streit, W. and Stone, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0952-5238}, Journal = {Vis Neurosci}, Keywords = {Embryo;Retina;Rats;Not relevant;Cell Count;Retinal Vessels;11 Glia;Animals, Newborn;Animals;Support, Non-U.S. Gov't;Phagocytosis}, Medline = {91120244}, Nlm_Id = {8809466}, Number = {5}, Organization = {Department of Anatomy, University of Sydney, NSW, Australia.}, Pages = {437-48}, Pubmed = {2487081}, Title = {The appearance and distribution of microglia in the developing retina of the rat}, Uuid = {5A1DCF21-9860-43D5-A09B-3869D4B22AF1}, Volume = {2}, Year = {1989}} @article{Ashwood-Smith:1985, Abstract = {Cryopreservation of chinese hamster ovary cells in tissue culture with either glycerol or dimethyl sulfoxide did not result in chromosome damage as measured by the sister chromatid exchange technique. These results are consistent with earlier negative reports in which the freezing and thawing of mammalian cells did not increase the frequency of micronuclei. No increases in the spontaneous mutation rates of several bacterial strains at different genetic loci were observed during the course of a number of years of storage at -196 degrees C. It is concluded that standard cryopreservation procedures are without genetic hazards. However, the well-documented effects of dimethyl sulfoxide on cell fusion and gene differentiation suggest caution in its use as a cryopreservative for animal and human embryos. 0011-2240 Journal Article}, Author = {Ashwood-Smith, M. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Cryobiology}, Keywords = {Cricetulus;Ovary;Sister Chromatid Exchange/*drug effects;Salmonella typhimurium/cytology/drug effects/*genetics;Glycerol/*pharmacology;EE, DMSO, abstr;Tissue Preservation/*methods;Female;Cell Line;08 Aberrant cell cycle;Escherichia coli/cytology/drug effects/*genetics;Dimethyl Sulfoxide/*pharmacology;Animals;Support, Non-U.S. Gov't;Hamsters;Freezing;*Mutation}, Number = {5}, Pages = {427-33}, Pubmed = {3902368}, Title = {Genetic damage is not produced by normal cryopreservation procedures involving either glycerol or dimethyl sulfoxide: a cautionary note, however, on possible effects of dimethyl sulfoxide}, Uuid = {8B040C13-8DE2-4442-A82F-5ECE2DCDAF4D}, Volume = {22}, Year = {1985}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3902368}} @article{Askovic:2001, Abstract = {The chimeric murine oncornavirus FrCas(E) causes a rapidly progressive paralytic disease associated with spongiform neurodegeneration throughout the neuroaxis. Neurovirulence is determined by the sequence of the viral envelope gene and by the capacity of the virus to infect microglia. The neurocytopathic effect of this virus appears to be indirect, since the cells which degenerate are not infected. In the present study we have examined the possible role of inflammatory responses in this disease and have used as a control the virus F43. F43 is an highly neuroinvasive but avirulent virus which differs from FrCas(E) only in 3' pol and env sequences. Like FrCas(E), F43 infects large numbers of microglial cells, but it does not induce spongiform neurodegeneration. RNAase protection assays were used to detect differential expression of genes encoding a variety of cytokines, chemokines, and inflammatory cell-specific markers. Tumor necrosis factor alpha (TNF-alpha) and TNF-beta mRNAs were upregulated in advanced stages of disease but not early, even in regions with prominent spongiosis. Surprisingly there was no evidence for upregulation of the cytokines interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-6 or of the microglial marker F4/80 at any stage of this disease. In contrast, increased levels of the beta-chemokines MIP-1 alpha and -beta were seen early in the disease and were concentrated in regions of the brain rich in spongiosis, and the magnitude of responses was similar to that observed in the brains of mice injected with the glutamatergic neurotoxin ibotenic acid. MIP-1alpha and MIP-1beta mRNAs were also upregulated in F43-inoculated mice, but the responses were three- to fivefold lower and occurred later in the course of infection than was observed in FrCas(E)-inoculated mice. These results suggest that the robust increase in expression of MIP-1 alpha and MIP-1 beta in the brain represents a correlate of neurovirulence in this disease, whereas the TNF responses are likely secondary events.}, Author = {Askovic, S. and Favara, C. and McAtee, F. J. and Portis, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Retroviridae Infections;Chemokines, CC;Virulence;Macrophage Inflammatory Protein-1;Ibotenic Acid;Neurodegenerative Diseases;Immunohistochemistry;Inflammation;Retroviridae;Not relevant;11 Glia;Cell Death;RNA, Messenger;Brain;Animals;Mice;Neurons}, Medline = {21126391}, Month = {3}, Nlm_Id = {0113724}, Number = {6}, Organization = {Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.}, Pages = {2665-74}, Pubmed = {11222690}, Title = {Increased expression of MIP-1 alpha and MIP-1 beta mRNAs in the brain correlates spatially and temporally with the spongiform neurodegeneration induced by a murine oncornavirus}, Uuid = {D3976495-DAC1-4C98-84D8-3F35CEEE9655}, Volume = {75}, Year = {2001}, url = {papers/Askovic_JVirol2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.75.6.2665-2674.2001}} @article{Assal:1993, Abstract = {Transient axons reaching the medialmost part of area 17 were demonstrated with anterogradely transported biocytin injected in the dorsal part of the lateral gyrus in kittens during the first and second postnatal weeks. The axons decreased in number during the third postnatal week and were only exceptionally found thereafter. Computer-aided reconstructions from serial sections demonstrated axons with different degrees of complexity. The most complex ones were found at postnatal days 7-9 and were characterized by multiple branches terminating with growth cones in the white matter. Characteristically, endings of axons that entered the cortex remained confined to the infragranular layers V and VI. A few axons entered the supragranular layers. Transient axons terminated with different endings, which may indicate different stages of maturation. A few, possibly permanent, axons were still found in the medial part of area 17 at the end of the first, and during the second postnatal months; they arborized widely in the infragranular layers, and modestly or not at all supragranularly.}, Author = {Assal, F. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Visual Cortex;Cats;Time Factors;Not relevant;Lysine;11 Glia;Medical Illustration;Animals, Newborn;Animals;Support, Non-U.S. Gov't;Axons}, Medline = {94003947}, Nlm_Id = {9110718}, Number = {4}, Organization = {Institute of Anatomy, Lausanne, Switzerland.}, Pages = {290-303}, Pubmed = {8400807}, Title = {Transient intra-areal axons in developing cat visual cortex}, Uuid = {0C6212F8-CF51-4565-8361-FA947C31ACA4}, Volume = {3}, Year = {1993}} @article{Atasoy:2008, Author = {Atasoy, Deniz and Aponte, Yexica and Su, Helen Hong and Sternson, Scott M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Animals;Photic Stimulation;Gene Expression Regulation;Humans;Image Processing, Computer-Assisted;Transfection;Rhodopsin;Dependovirus;Diagnostic Imaging;Cell Line, Transformed;Patch-Clamp Techniques;Mice, Transgenic;Green Fluorescent Proteins;research support, non-u.s. gov't;Nerve Net;Membrane Potentials;6-Cyano-7-nitroquinoxaline-2,3-dione;Mice;24 Pubmed search results 2008;Arcuate Nucleus;Brain Mapping}, Month = {7}, Nlm_Id = {8102140}, Number = {28}, Organization = {Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.}, Pages = {7025-30}, Pii = {28/28/7025}, Pubmed = {18614669}, Title = {A FLEX switch targets Channelrhodopsin-2 to multiple cell types for imaging and long-range circuit mapping}, Uuid = {8C0E2A74-601B-4527-8FE3-F6450218BA52}, Volume = {28}, Year = {2008}, url = {papers/Atasoy_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1954-08.2008}} @article{Athanassakis:2002, Abstract = {The development, growth and regeneration of nerve cells remain an unresolved issue. The up-to-date reported brain repair mechanisms are numerous and evidence suggests that, apart from the required trophism, tropism, microenvironment and specificity of the brain, a plethora of chemical, physiological and immunological compounds can contribute to such events. Among these compounds, we concentrated our interest on L- carnitine (L-Cn), which regulates the beta-oxidation of long chain fatty acids necessary for brain development, myelinization and growth. In contrast to fetal brain cells that grow easily in culture, adult brain cells show limited neurogenesis. Here, using adult brain cells from experimental mice, we show that although L-Cn does not improve their proliferative activity in short-term cultures, it accelerates the growth and differentiation of neurons, astrocytes, oligodendrocytes and ependymal cells from neurospheres in long-term cultures. Thus, the formation of a confluent neural network requires a 2-month period in culture. These observations provide new insights for in vivo use of L- Cn to support brain cell development in cases of injury or brain degenerative diseases.}, Author = {Athanassakis, I. and Zarifi, I. and Evangeliou, A. and Vassiliadis, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Brain Res}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {1-2}, Organization = {Department of Biology, University of Crete, P.O. Box 2208, 714-09, Crete, Heraklion, Greece}, Pages = {70-8.}, Title = {L-Carnitine accelerates the in vitro regeneration of neural network from adult murine brain cells}, Uuid = {9513C52D-4A71-4829-89F2-EAFEB96F0758}, Volume = {932}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11911863}} @article{Au:2006, Author = {Au, Edmund and Fishell, Gord}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008;Flow Cytometry;Adult;Cell Proliferation;DNA;Animals;Humans;Cerebral Cortex;Neurons;news}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Pages = {1086-8}, Pii = {nn0906-1086}, Pubmed = {16936768}, Title = {Adult cortical neurogenesis: nuanced, negligible or nonexistent?}, Uuid = {4AB50BD3-84F8-4F42-9DF4-24C33D4187F4}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0906-1086}} @article{Avoli:1987, Abstract = {Seizure-like discharges were observed in slices of human epileptogenic neocortex maintained in vitro when [Mg2+]o was lowered near to zero. This type of epileptiform activity: (1) could occur spontaneously or following extracellular focal stimuli; (2) resembled the electrographic pattern associated with tonic-clonic seizures; (3) was accompanied by increases in [K+]o (maximally 6.2 mM from a baseline of 3.25 mM) and decreases in [Ca2+]o (maximally 0.23 mM from a baseline of 1.8 mM). Application of the selective antagonist of N-methyl-D-aspartate (NMDA) receptors, DL-2-amino-5-phosphonovalerate, suppressed in a reversible manner both spontaneous and stimulus-induced seizure-like discharges, suggesting that NMDA-activated conductances are important for the genesis of prolonged epileptiform discharges generated by human epileptogenic neocortical slices.}, Author = {Avoli, M. and Louvel, J. and Pumain, R. and Olivier, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Gyrus Cinguli;Epilepsies, Partial;10 Development;research support, non-u.s. gov't;21 Neurophysiology;Magnesium;in vitro;10 genetics malformation;Receptors, Neurotransmitter;Humans;Receptors, N-Methyl-D-Aspartate;Temporal Lobe;24 Pubmed search results 2008;21 Epilepsy}, Month = {8}, Nlm_Id = {0045503}, Number = {1}, Pages = {199-203}, Pubmed = {3040183}, Title = {Seizure-like discharges induced by lowering [Mg2+]o in the human epileptogenic neocortex maintained in vitro}, Uuid = {7886D4E9-E192-46DA-9F44-12B3AEE7FA17}, Volume = {417}, Year = {1987}} @article{Avoli:1987a, Abstract = {Intracellular recordings from hippocampal pyramidal cells in the CA1 subfield of the 'in vitro' slice in the presence of 4-aminopyridine (4-AP, 5-50 microM) revealed a long-lasting (up to 1.5 s) depolarizing potential which occurred either spontaneously or following orthodromic stimulation. This potential was: capable of blocking both direct and synaptic activation of the cell; sensitive to bath application of low concentrations of bicuculline methiodide; and associated to an extracellular current sink in the dendrites as suggested by the extracellular field potentials recorded at different levels along an axis perpendicular to the stratum pyramidale. It is concluded that the long-lasting depolarizing potential evoked by 4-AP is caused by the activation of GABA receptors localized in the dendritic region of the CA1 subfield.}, Author = {Avoli, M. and Perreault, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {21 Epilepsy;10 Development;research support, non-u.s. gov't;21 Neurophysiology;Bicuculline;4-Aminopyridine;Action Potentials;Hippocampus;Rats;in vitro;Evoked Potentials;10 genetics malformation;Aminopyridines;Animals;Membrane Potentials;24 Pubmed search results 2008;Receptors, GABA-A}, Month = {1}, Nlm_Id = {0045503}, Number = {1}, Pages = {191-5}, Pii = {0006-8993(87)90671-8}, Pubmed = {3028566}, Title = {A GABAergic depolarizing potential in the hippocampus disclosed by the convulsant 4-aminopyridine}, Uuid = {746545A3-2FCE-4599-BE18-124878149B7F}, Volume = {400}, Year = {1987}} @article{Avoli:1991, Abstract = {In this review we summarize a number of technical and methodological approaches that have been used in our laboratory to study human brain slices maintained in vitro. The findings obtained in the course of these studies appear to be relevant in establishing the mechanisms that underlie physiological phenomena of the human brain such as synaptic plasticity or responses to neuroactive drugs. Moreover, these data are important for understanding certain fundamental mechanisms of epilepsy. In this respect, however, we caution that the mechanisms that apply to different forms of clinical epilepsy might be difficult to find given the variability present in the pathogenesis of human epilepsy.}, Author = {Avoli, M. and Hwa, G. G. and Kostopoulos, G. and Olivier, A. and Villemure, J. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0317-1671}, Journal = {Can J Neurol Sci}, Keywords = {Epilepsy;21 Epilepsy;Electroencephalography;Research Support, Non-U.S. Gov't;21 Neurophysiology;In Vitro;Electrophysiology;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Medline = {92136245}, Month = {11}, Nlm_Id = {0415227}, Number = {4 Suppl}, Organization = {Montreal Neurological Institute, Quebec, Canada.}, Pages = {636-9}, Pubmed = {1777884}, Title = {Electrophysiological analysis of human neocortex in vitro: experimental techniques and methodological approaches}, Uuid = {ACF89C77-4A1A-4FF3-95C3-25A8559419EF}, Volume = {18}, Year = {1991}} @article{Avoli:2003, Abstract = {Taylor's focal cortical dysplasia corresponds to a localized disruption of the normal cortical lamination with an excess of large, aberrant cells. Sustained epileptic discharges originate from the dysplastic neocortex and this tissue retains sufficient connectivity for expressing seizure abnormalities. In this brief review, we summarize the findings obtained by analyzing surgically-resected human tissue with focal cortical dysplasia that was maintained in vitro in a brain slice preparation. These data have been compared with those obtained from human cortex with normal structural organization; such tissue was available from patients undergoing surgery for a variety of neurological disorders, most often for mesial temporal lobe epilepsy. These studies have shown that: (i). slices obtained from focal cortical dysplastic tissue have an intrinsic ability to generate ictal-like epileptiform events when challenged with the convulsant drug 4-aminopyridine; (ii). 4-aminopyridine-induced ictal discharges are not seen in neocortical slices obtained from neocortical samples with no or minimal structural lesion; (iii). these ictal discharges are caused by the activation of excitatory amino acid receptors, and in particular those of the N-methyl-D aspartate type; (iv). focal cortical dysplastic tissue also generates synchronous potentials that are mainly contributed by GABA(A) receptor-mediated conductances.}, Author = {Avoli, Massimo and Louvel, Jacques and Mattia, Donatella and Olivier, Andre and Esposito, Vincenzo and Pumain, Rene and D'Antuono, Margherita}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {1294-9361}, Journal = {Epileptic Disord}, Keywords = {Epilepsy;24 Pubmed search results 2008;21 Epilepsy;10 Development;21 Dysplasia-heterotopia;21 Neurophysiology;Magnetic Resonance Imaging;Research Support, Non-U.S. Gov't;4-Aminopyridine;Receptors, AMPA;10 genetics malformation;Receptors, N-Methyl-D-Aspartate;Humans;Cerebral Cortex;review;Receptors, GABA-A}, Medline = {22982194}, Month = {9}, Nlm_Id = {100891853}, Organization = {Department of Neurology & Neurosurgery, McGill University, Montr{\'e}al, Qu{\'e}bec, H3A 2B4, Canada. massimo.avoli\@mcgill.ca}, Pages = {S45-50}, Pubmed = {14617420}, Title = {Epileptiform synchronization in the human dysplastic cortex}, Uuid = {826EC9F8-95FD-409C-A522-75C5C59EB2A8}, Volume = {5 Suppl 2}, Year = {2003}} @article{Avoli:1996, Abstract = {The availability of neocortical tissue obtained during brain surgery has allowed for detailed studies of the membrane and synaptic properties of neurons maintained in vitro in a slice preparation. Many of the findings obtained in these studies are summarized here. The majority of the basic electrophysiological properties appear to be similar when human and rodent neurons are compared. However, some notable exceptions regarding specific membrane properties have been reported. Since the majority of the material used in these studies is obtained from epileptic patients, several neuroscientists have tried to determine whether this tissue retains any sign of epileptogenicity when analyzed in vitro. Abnormal synaptic activity was only seen in a fraction of neurons near identified anatomical foci, including tumors, or within neocortical areas that displayed abnormal electrographic activity in situ. This cellular activity included both the presence of all-or-none and graded synaptic bursts. Epileptiform activity comparable to that seen in rodent tissue has been obtained in vitro using several pharmacological procedures including the disinhibition and the Mg(2+)-free model. In conclusion, electrophysiological and pharmacological studies of the human neocortex obtained during surgery have so far been unsuccessful in isolating any definite cellular mechanism that may account for the expression of the epileptiform activity in situ. Nevertheless, these studies have provided valuable information on the cellular and synaptic properties of human neocortex under normal conditions, and following experimental procedures capable of increasing neuronal excitability.}, Author = {Avoli, M. and Williamson, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {24 Pubmed search results 2008;21 Epilepsy;Research Support, Non-U.S. Gov't;21 Neurophysiology;Electrophysiology;Cells, Cultured;Humans;Cerebral Cortex;review;Neurons}, Medline = {96405778}, Month = {4}, Nlm_Id = {0370121}, Number = {6}, Organization = {Montreal Neurological Institute, McGill University, Quebec, Canada.}, Pages = {519-54}, Pii = {030100829500050X}, Pubmed = {8809907}, Title = {Functional and pharmacological properties of human neocortical neurons maintained in vitro}, Uuid = {4C03AF28-D20A-454E-A80D-1947CF2764E9}, Volume = {48}, Year = {1996}} @article{Awasaki:2004, Abstract = {BACKGROUND: Axon pruning is involved in establishment and maintenance of functional neural circuits. During metamorphosis of Drosophila, selective pruning of larval axons is developmentally regulated by ecdysone and caused by local axon degeneration. Previous studies have revealed intrinsic molecular and cellular mechanisms that trigger this pruning process, but how pruning is accomplished remains essentially unknown. RESULTS: Detailed analysis of morphological changes in the axon branches of Drosophila mushroom body (MB) neurons revealed that during early pupal stages, clusters of neighboring varicosities, each of which belongs to different axons, disappear simultaneously shortly before the onset of local axon degeneration. At this stage, bundles of axon branches are infiltrated by the processes of surrounding glia. These processes engulf clusters of varicosities and accumulate intracellular degradative compartments. Selective inhibition of cellular functions, including endocytosis, in glial cells via the temperature-sensitive allele of shibire both suppresses glial infiltration and varicosity elimination and induces a severe delay in axon pruning. Selective inhibition of ecdysone receptors in the MB neurons severely suppressed not only axon pruning but also the infiltration and engulfing action of the surrounding glia. CONCLUSIONS: These findings strongly suggest that glial cells are extrinsically activated by ecdysone-stimulated MB neurons. These glial cells infiltrate the mass of axon branches to eliminate varicosities and break down axon branches actively rather than just scavenging already-degraded debris. We therefore propose that neuron-glia interaction is essential for the precisely coordinated axon-pruning process during Drosophila metamorphosis.}, Author = {Awasaki, Takeshi and Ito, Kei}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Ecdysone;Nerve Degeneration;Motor Neurons, Gamma;Pupa;Animals;Mushroom Bodies;Comparative Study;Dynamins;Axons;Alleles;Endocytosis;Neuroglia;Receptors, Steroid;Metamorphosis, Biological;Drosophila;Immunohistochemistry;24 Pubmed search results 2008;Gene Expression;Drosophila Proteins;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {9107782}, Number = {8}, Organization = {Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. awasaki\@iam.u-tokyo.ac.jp}, Pages = {668-77}, Pii = {S0960982204002544}, Pubmed = {15084281}, Title = {Engulfing action of glial cells is required for programmed axon pruning during Drosophila metamorphosis}, Uuid = {534123D7-00AB-11DB-9E68-000D9346EC2A}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2004.04.001}} @article{Awasaki:2006, Abstract = {Axon pruning is a common phenomenon in neural circuit development. Previous studies demonstrate that the engulfing action of glial cells is essential in this process. The underlying molecular mechanisms, however, remain unknown. We show that draper (drpr) and ced-6, which are essential for the clearance of apoptotic cells in C. elegans, function in the glial engulfment of larval axons during Drosophila metamorphosis. The drpr mutation and glia-specific knockdown of drpr and ced-6 by RNA interference suppress glial engulfment, resulting in the inhibition of axon pruning. drpr and ced-6 interact genetically in the glial action. Disruption of the microtubule cytoskeleton in the axons to be pruned occurs via ecdysone signaling, independent of glial engulfment. These findings suggest that glial cells engulf degenerating axons through drpr and ced-6. We propose that apoptotic cells and degenerating axons of living neurons are removed by a similar molecular mechanism.}, Author = {Awasaki, Takeshi and Tatsumi, Ryoko and Takahashi, Kuniaki and Arai, Kunizo and Nakanishi, Yoshinobu and Ueda, Ryu and Ito, Kei}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Animals;Gene Expression Regulation, Developmental;Rats;10 Structural plasticity;Phosphoproteins;Apoptosis;Axons;Animals, Genetically Modified;comparative study ;research support, non-u.s. gov't ;Nerve Net;Drosophila;Metamorphosis, Biological;Caenorhabditis elegans Proteins;24 Pubmed search results 2008;Membrane Proteins;Drosophila Proteins}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan. takeshi.awasaki\@umassmed.edu}, Pages = {855-67}, Pii = {S0896-6273(06)00318-7}, Pubmed = {16772168}, Title = {Essential role of the apoptotic cell engulfment genes draper and ced-6 in programmed axon pruning during Drosophila metamorphosis}, Uuid = {F0D360F1-DAA9-4631-97E7-82FE383861DF}, Volume = {50}, Year = {2006}, url = {papers/Awasaki_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.04.027}} @article{Axelrod:2006, Abstract = {The evolution of cooperation has a well established theoretical framework based on game theory. This approach has made valuable contributions to a wide variety of disciplines, including political science, economics, and evolutionary biology. Existing cancer theory suggests that individual clones of cancer cells evolve independently from one another, acquiring all of the genetic traits or hallmarks necessary to form a malignant tumor. It is also now recognized that tumors are heterotypic, with cancer cells interacting with normal stromal cells within the tissue microenvironment, including endothelial, stromal, and nerve cells. This tumor cell-stromal cell interaction in itself is a form of commensalism, because it has been demonstrated that these nonmalignant cells support and even enable tumor growth. Here, we add to this theory by regarding tumor cells as game players whose interactions help to determine their Darwinian fitness. We marshal evidence that tumor cells overcome certain host defenses by means of diffusible products. Our original contribution is to raise the possibility that two nearby cells can protect each other from a set of host defenses that neither could survive alone. Cooperation can evolve as by-product mutualism among genetically diverse tumor cells. Our hypothesis supplements, but does not supplant, the traditional view of carcinogenesis in which one clonal population of cells develops all of the necessary genetic traits independently to form a tumor. Cooperation through the sharing of diffusible products raises new questions about tumorigenesis and has implications for understanding observed phenomena, designing new experiments, and developing new therapeutic approaches.}, Author = {Axelrod, Robert and Axelrod, David E. and Pienta, Kenneth J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Models, Biological;Cell Transformation, Neoplastic;research support, n.i.h., extramural ;research support, non-u.s. gov't ;09 Evolutionary dynamics;22 Stem cells;research support, u.s. gov't, non-p.h.s. ;Evolution;Game Theory;Humans;Neoplasms;22 Cancer;review;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {7505876}, Number = {36}, Organization = {Gerald R. Ford School of Public Policy and Department of Political Science, University of Michigan, Ann Arbor, MI 48109, USA.}, Pages = {13474-9}, Pii = {0606053103}, Pubmed = {16938860}, Title = {Evolution of cooperation among tumor cells}, Uuid = {7D593FF4-0149-4CD5-822A-B54591F4A19A}, Volume = {103}, Year = {2006}, url = {papers/Axelrod_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0606053103}} @article{Ayala:2007, Abstract = {The correct positioning of neurons during development--achieved through directed migration--is the basis for proper brain function. Several decades of research have yielded a comprehensive map illustrating the temporal and spatial events underlying neurogenesis and neuronal migration during development. The discovery of distinct migration modes and pathways has been accompanied by the identification of a large interwoven molecular network that transmits extracellular signals into the cell. Moreover, recent work has shed new light on how the cytoskeleton is regulated and coordinated at the molecular and cellular level to execute neuronal migration.}, Author = {Ayala, Rams{\'e}s and Shu, Tianzhi and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Neurons;24 Pubmed search results 2008;10 Development;Cytoskeleton;Signal Transduction;Protein Kinases;Animals;Brain;Cell Movement;review;Humans}, Month = {1}, Nlm_Id = {0413066}, Number = {1}, Organization = {Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Cambridge, MA 02139, USA.}, Pages = {29-43}, Pii = {S0092-8674(06)01648-5}, Pubmed = {17218253}, Title = {Trekking across the brain: the journey of neuronal migration}, Uuid = {751C197D-0524-46E5-898B-CEF60525B832}, Volume = {128}, Year = {2007}, url = {papers/Ayala_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.12.021}} @article{Ayoub:2003, Abstract = {Microglia are the immune cells of the CNS. In the normal adult mammalian brain, the majority of these cells is quiescent and exhibits a ramified morphology. Microglia are perhaps best known for their swift transformation to an activated ameboid morphology in response to pathological insults. Here we have observed the responsiveness of these cells to events surrounding the normal activation of neurosecretory neurons in the hypothalamic supraoptic nucleus (SON), a well studied model of structural plasticity in the CNS. Neurons in the SON were activated by substituting 2\%saline for drinking water. Brain sections were collected from four experimental groups [controls (C), 2 d-dehydrated (2D), 7 d-dehydrated (D7), and 7 d-dehydrated/21 d-rehydrated animals (R21)] and stained with Isolectin-B4-HRP to visualize microglial cells. Based on morphological criteria, we quantified ramified, hypertrophied, and ameboid microglia using unbiased stereological techniques. Statistical analyses showed significant increases in the number of hypertrophied microglia in the D2 and D7 groups. Moreover, there was a significant increase in the number of ameboid microglia in the D7 group. No changes were seen across conditions in the number of ramified cells, nor did we observe any significant phenotypic changes in a control area of the cingulate gyrus. Hence, increased morphological diversity of microglia was found specifically in the SON and was reversible with the cessation of stimulation. These results indicate that phenotypic plasticity of microglia may be a feature of the normal structural remodeling that accompanies neuronal activation in addition to the activation that accompanies brain pathology.}, Author = {Ayoub, Albert E. and Salm, A. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Gyrus Cinguli;Cell Size;Rats, Sprague-Dawley;Rats;Supraoptic Nucleus;Phenotype;Not relevant;11 Glia;Support, U.S. Gov't, Non-P.H.S.;Microglia;Male;Animals}, Medline = {22825257}, Month = {8}, Nlm_Id = {8102140}, Number = {21}, Organization = {Department of Neurobiology and Anatomy, West Virginia University School of Medicine, Morgantown, West Virginia 26506-9128, USA.}, Pages = {7759-66}, Pii = {23/21/7759}, Pubmed = {12944504}, Title = {Increased morphological diversity of microglia in the activated hypothalamic supraoptic nucleus}, Uuid = {48B73CDB-CF44-4776-8417-86AC5EF30EBC}, Volume = {23}, Year = {2003}, url = {papers/Ayoub_JNeurosci2003.pdf}} @article{Azzam:2004, Abstract = {Budding yeast protein phosphatase Cdc14 is sequestered in the nucleolus in an inactive state during interphase by the anchor protein Net1. Upon entry into anaphase, the Cdc14 early anaphase release (FEAR) network initiates dispersal of active Cdc14 throughout the cell. We report that the FEARnetwork promotes phosphorylation of Net1 by cyclin-dependent kinase (Cdk) complexed with cyclin B1 or cyclin B2. These phosphorylations appear to be required for FEAR and sustain the proper timing of late mitotic events. Thus, a regulatory circuit exists to ensure that the arbiter of the mitotic state, Cdk, sets in motion events that culminate in exit from mitosis.}, Author = {Azzam, Ramzi and Chen, Susan L. and Shou, Wenying and Mah, Angie S. and Alexandru, Gabriela and Nasmyth, Kim and Annan, Roland S. and Carr, Steven A. and Deshaies, Raymond J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:41 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {10 Development;Cell Cycle Proteins;Phosphorylation;DNA, Ribosomal;Recombinant Proteins;Metaphase;Mitosis;Mutation;Protein Kinases;Meiosis;Cyclin B;Support, Non-U.S. Gov't;Saccharomyces cerevisiae Proteins;Saccharomyces cerevisiae;Cell Nucleolus;Support, U.S. Gov't, P.H.S.;Protein-Tyrosine-Phosphatase;Cyclin-Dependent Kinases;Anaphase;Nuclear Proteins}, Month = {7}, Nlm_Id = {0404511}, Number = {5683}, Organization = {Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.}, Pages = {516-9}, Pii = {305/5683/516}, Pubmed = {15273393}, Title = {Phosphorylation by cyclin B-Cdk underlies release of mitotic exit activator Cdc14 from the nucleolus}, Uuid = {9BA0C2A1-58AF-4A7F-88CE-5838C67360F5}, Volume = {305}, Year = {2004}, url = {papers/Azzam_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1099402}} @article{Baba:1997, Abstract = {In the main olfactory bulb, neurons are arranged strategically in distinct layers among which translaminar synaptic transmission can be made from the superficial, sensory to the deep, output layers that account for the processing of olfactory information. To search for stimulus-transcription coupling thought to be operated differentially in several cell types, c-Jun expression was examined immunohistochemically in rat olfactory bulb following 30-min odor stimulation with acetic acid and 1-butanol. c-Jun was rapidly induced in neuronal cell nuclei belonging to periglomerular, tufted, mitral and granule cells. The disappearance of c-Jun, however, differed between each cell type. In the glomerular layer, the glomeruli composed of c- Jun-expressing periglomerular cells were seen. Different odors led to labeling of different sets of glomeruli. The labeled periglomerular cells disappeared within 2 h. In all the deeper layers, however, a rather homogeneous label was noted for the tufted, mitral and granule cells present throughout the olfactory bulb, regardless of the difference in odor. In tufted and mitral cells, the c-Jun expression persisted for 4 days after odor stimulation. In the granule cell layer, numerous granule cells increased c-Jun immunoreactivity which lasted for 1 day following odor application. In control rats which were given clean air, the basal amount of c-Jun expression was seen confined to scattered granule cells. The results suggest that c-Jun is expressed in a variety of odorant-stimulated bulb neurons with a time course being dependent on cell type.}, Author = {Baba, K. and Ikeda, M. and Houtani, T. and Nakagawa, H. and Ueyama, T. and Sato, K. and Sakuma, S. and Yamashita, T. and Tsukahara, Y. and Sugimoto, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {Brain Res}, Keywords = {Tissue Distribution;Rats, Sprague-Dawley;Neurons, Afferent/drug effects/*metabolism;Olfactory Bulb/cytology/drug effects/*metabolism;Proto-Oncogene Proteins c-jun/*metabolism;Rats;1-Butanol/pharmacology;*Odors;Stimulation, Chemical;Acetic Acid/pharmacology;Animal;I abstr;Support, Non-U.S. Gov't;Male;13 Olfactory bulb anatomy}, Number = {1-2}, Organization = {Department of Anatomy, Kansai Medical University, Moriguchi, Osaka, Japan.}, Pages = {142-8.}, Title = {Odor exposure reveals non-uniform expression profiles of c-Jun protein in rat olfactory bulb neurons}, Uuid = {1B19770D-1234-4C85-9BCC-22DAF371525D}, Volume = {774}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9452202}} @article{Baba:2004, Abstract = {BACKGROUND/AIMS: Recently, several cells found within the liver have been reported to derive from bone marrow (BM). This study sought to examine the commitment of BM cells to hepatic stellate cell (HSC) lineage in mouse liver. METHODS: We transplanted BM cells from green fluorescent protein (GFP) transgenic mice into age-matched C57BL/J mice. Hepatic nonparenchymal cells were isolated from the livers of BM-transplanted mice using density gradient centrifugation with Nycodenz. The expression of lineage markers by the isolated cells was evaluated by RT-PCR and immunostaining. We then examined the histology of liver tissues obtained from BM-transplanted mice with and without carbon tetrachloride-induced injury. RESULTS: GFP-expressing cells with intracytoplasmic lipid droplets comprised 33.4 +/- 2.3\%of the cells isolated by density gradient centrifugation. These cells expressed the HSC lineage markers, such as desmin and glial fibrillary acidic protein (GFAP), by both RT-PCR and immunostaining. During a 7-day culture, GFP-positive cells began to express alpha-smooth muscle actin, a marker of activated HSC. In the liver of BM-transplanted mice, GFP-positive nonparenchymal cells expressed GFAP and extended their process around hepatocytes. Upon liver injury, these cells also co-expressed desmin and alpha-smooth muscle actin. CONCLUSIONS: Nonparenchymal cells, derived from transplanted BM, acquired HSC characteristics in both quiescent and activated states.}, Author = {Baba, Shinji and Fujii, Hideaki and Hirose, Tetsuro and Yasuchika, Kentaro and Azuma, Hisaya and Hoppo, Toshitaka and Naito, Masato and Machimoto, Takafumi and Ikai, Iwao}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:26 -0400}, Issn = {0168-8278}, Journal = {J Hepatol}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Cells, Cultured;Bone Marrow Transplantation;Mice, Transgenic;Liver;Mice, Inbred C57BL;11 Glia;Liver Diseases;Reverse Transcriptase Polymerase Chain Reaction;Green Fluorescent Proteins;Bone Marrow Cells;Cell Lineage;Liver Regeneration;Mice;Genes, Reporter;Luminescent Proteins;Immunohistochemistry;Carbon Tetrachloride}, Month = {2}, Nlm_Id = {8503886}, Number = {2}, Organization = {Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, 54 Kawara-cho, Shogoin, Sakyo-ku, Kyoto City 606-8507, Japan. barbee\@kuhp.kyoto-u.ac.jp}, Pages = {255-60}, Pii = {S0168827803005312}, Pubmed = {14739096}, Title = {Commitment of bone marrow cells to hepatic stellate cells in mouse}, Uuid = {12C9C747-8495-4A26-9349-E02B75641BE6}, Volume = {40}, Year = {2004}} @article{Babb:1998, Abstract = {Developmental disorders of neuronal migrations in the human brain are referred to as 'cortical dysplasia', and current knowledge of cortical dysplasia is limited to varied pathologic descriptions which lack specific investigations of glutamate receptor mechanisms. In this study, immunocytochemistry was used to study the expressions of glutamate receptor subunit proteins for NMDAR2A/B, NMDAR1 and AMPA Glu-R2/3 in human brain resected for intractable epilepsy associated with cortical dysplasia. Seventeen patients were studied with batch-matched glutamate subunit reagents on adjacent 30-microm sections. The most striking microscopic abnormalities identified in cresylecht violet stains were cortical dyslaminations, disoriented neurons, and unexpectedly, very dark Nissl body staining of those dysplastic neurons. NMDAR2A/B intensely labeled dysplastic neurons, showing staining in both the cell bodies and dendritic profiles. However, non-dysplastic neurons were not immunoreactive to NMDAR2A/B. Dysplastic neurons were also labeled by antibodies selective to NMDAR1. Both dysplastic neurons and non-dysplastic neurons were immunoreactive to AMPA GluR2/3. Our results suggest that the epileptic hyperexcitability of dysplastic cortical regions may result, at least in part, from the heteromeric coassembly and expressions of NMDAR2A/B subunits with selectively expressed NMDAR1 splice variants in dysplastic neurons. AMPA receptors are probably also essential but not sufficient to explain the 'epileptic' properties of these dysplastic neurons. A longer, detailed report of some of these findings have been previously published (Ying et al., 1998. J. Neuropathol. Exp. Neurol. 57, 47-62).}, Author = {Babb, T. L. and Ying, Z. and Hadam, J. and Penrod, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:40 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {10 Development;Receptors, Glutamate;Child, Preschool;Humans;Middle Aged;Variation (Genetics);Alternative Splicing;Brain;Child;Epilepsy;Receptors, AMPA;Aged;10 genetics malformation;research support, u.s. gov't, p.h.s.;Cerebral Cortex;Adult;Neurons;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Adolescent}, Month = {9}, Nlm_Id = {8703089}, Number = {1-2}, Organization = {Department of Neurosciences, The Cleveland Clinic Foundation, OH 44195, USA. babbt\@cesmtp.ccf.org}, Pages = {24-33}, Pii = {S0920-1211(98)00037-0}, Pubmed = {9761306}, Title = {Glutamate receptor mechanisms in human epileptic dysplastic cortex}, Uuid = {E2FDD3AD-F596-4A5D-9B7B-F711CB7FEB6A}, Volume = {32}, Year = {1998}, url = {papers/Babb_EpilepsyRes1998.pdf}} @article{Badea:2001, Abstract = {Epileptic discharges propagate through apparently normal circuits, although it is still unclear how this recruitment takes place. To understand the role of different classes of neurons in neocortical epilepsy, we have developed a novel imaging assay that detects which neurons participate in epileptiform discharges. Using calcium imaging of neuronal populations during bicuculline-induced spontaneous epileptiform events in slices from juvenile mouse somatosensory cortex, we find that fast calcium transients correlate with epileptiform field potentials and intracellular depolarizing shifts and can be used as an optical signature that a given neuron has participated in an epileptiform event. Our results demonstrate a novel method to characterize epileptiform events with single-cell resolution. In addition, our data are consistent with an important role for layer 5 in generating neocortical seizures and indicate that subgroups of neurons are particularly prone to epileptiform recruitment.}, Author = {Badea, T. and Goldberg, J. and Mao, B. and Yuste, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Mice, Inbred BALB C;Fura-2;Electrophysiology;Animals;21 Epilepsy;Epilepsy;Reaction Time;Mice, Inbred C57BL;Calcium;Tetrodotoxin;Microscopy, Fluorescence;Bicuculline;21 Calcium imaging;Research Support, U.S. Gov't, P.H.S.;Action Potentials;Cerebral Cortex;21 Neurophysiology;Neurons;Convulsants;Mice;24 Pubmed search results 2008;Intracellular Membranes;Research Support, Non-U.S. Gov't}, Medline = {21359630}, Month = {9}, Nlm_Id = {0213640}, Number = {3}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {215-27}, Pii = {10.1002/neu.1052}, Pubmed = {11466708}, Title = {Calcium imaging of epileptiform events with single-cell resolution}, Uuid = {673CEEBA-0145-11DB-9E68-000D9346EC2A}, Volume = {48}, Year = {2001}, url = {papers/Badea_JNeurobiol2001.pdf}} @article{Bae:2005, Abstract = {After transplantation, adult bone marrow-derived mesenchymal stem cells (BM-MSCs) may undergo transdifferentiation and/or cell fusion in response to new environments. However, the mechanism(s) that govern these cell fate switches remain unknown. Here we demonstrate that the pathology associated with murine Niemann- Pick disease type C (NP-C) cerebellum augments the ability of BM-MSCs to fuse with Purkinje neurons. The results suggest that the degenerative microenvironment of Purkinje neurons in the NP-C cerebellum modulates the cell fate switch of BM-MSCs via cell fusion.}, Author = {Bae, and Furuya, and Shinoda, and Endo, and Schuchman, and Hirabayashi, and Jin,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1043-0342}, Journal = {Hum Gene Ther}, Keywords = {11 Glia}, Month = {6}, Nlm_Id = {9008950}, Notes = {cell fusion, degeneration, dendrites neurons}, Organization = {College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, South Korea.}, Pubmed = {16029138}, Title = {Neurodegeneration Augments the Ability of Bone Marrow-Derived Mesenchymal Stem Cells to Fuse with Purkinje Neurons in Niemann-Pick Type C Mice}, Uuid = {6B4B22DB-B49D-4217-953F-25612CD7A527}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/hum.2005.16.ft-97}} @article{Bagri:2002, Abstract = {The dentate gyrus is the primary afferent pathway into the hippocampus, but there is little information concerning the molecular influences that govern its formation. In particular, the control of migration and cell positioning of dentate granule cells is not clear. We have characterized more fully the timing and route of granule cell migration during embryogenesis using in utero retroviral injections. Using this information, we developed an in vitro assay that faithfully recapitulates important events in dentate gyrus morphogenesis. In searching for candidate ligands that may regulate dentate granule cell migration, we found that SDF1, a chemokine that regulates cerebellar and leukocyte migration, and its receptor CXCR4 are expressed in patterns that suggest a role in dentate granule cell migration. Furthermore, CXCR4 mutant mice have a defect in granule cell position. Ectopic expression of SDF1 in our explant assay showed that it directly regulates dentate granule cell migration. Our study shows that a chemokine is necessary for the normal development of the dentate gyrus, a forebrain structure crucial for learning and memory.}, Author = {Bagri, Anil and Gurney, Theresa and He, Xiaoping and Zou, Yong-Rui R. and Littman, Dan R. and Tessier-Lavigne, Marc and Pleasure, Samuel J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Organ Culture Techniques;Gestational Age;Stromal Cells;Mice, Knockout;Research Support, Non-U.S. Gov't;Embryonic and Fetal Development;Chemokines, CXC;Female;Dentate Gyrus;Research Support, U.S. Gov't, P.H.S.;Pregnancy;Morphogenesis;Mice;Cell Movement;Animals;Neurons;Receptors, CXCR4}, Medline = {22170647}, Month = {9}, Nlm_Id = {8701744}, Number = {18}, Organization = {Neurodevelopmental Disorders Laboratory, Department of Neurology, Program in Neuroscience, University of California, San Francisco, CA 94143-0435, USA.}, Pages = {4249-60}, Pubmed = {12183377}, Title = {The chemokine SDF1 regulates migration of dentate granule cells}, Uuid = {2415FE0C-7114-11DA-9A4D-000D9346EC2A}, Volume = {129}, Year = {2002}, url = {papers/Bagri_Development2002.pdf}} @article{Bahrey:2003, Abstract = {We measured dye coupling, electrical coupling, and voltage-gated currents using whole-cell voltage clamp in slices of mouse sensorimotor cortex at embryonic day 14 (E14). As in rat ventricular zone (VZ), cells of the VZ were extensively dye coupled, often in clusters of >100 cells. In mouse VZ, however, cells were much less electrically coupled, making measurement of voltage-gated currents more accurate. All VZ cells expressed delayed K(+) currents (I(K)), and 30\%, including morphologically identified radial glia, also expressed inward Na(+) currents (I(Na)). This fraction is consistent with I(Na) expression being an early event following cell cycle exit. Intermediate zone (IZ) cells also expressed I(K) and I(Na). Na(+) current amplitude distributions indicated three populations of IZ cells: those without I(Na), those with I(Na) similar in amplitude to VZ cells, and those with I(Na) being almost 10 times larger than in VZ cells. Cells of the cortical plate (CP) expressed both I(K) and I(Na), with I(Na) being almost 10-fold larger than in VZ cells. No cell in any zone expressed detectable hyperpolarization-activated currents. Our data suggest that the distribution and density of I(Na) may be related to early events of cell cycle exit and migration.}, Author = {Bahrey, Heidi L. Picken and Moody, William J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Embryo;research support, u.s. gov't, p.h.s. ;Ion Channels;21 Neurophysiology;Action Potentials;Female;Mice, Inbred C57BL;Fluorescent Dyes;Neocortex;21 Circuit structure-function;research support, u.s. gov't, non-p.h.s. ;Pregnancy;Animals;Mice;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {9110718}, Number = {3}, Organization = {Department of Zoology, University of Washington, Seattle, WA 98195, USA.}, Pages = {239-51}, Pubmed = {12571114}, Title = {Voltage-gated currents, dye and electrical coupling in the embryonic mouse neocortex}, Uuid = {7B344526-7A5A-4275-9EB1-A7B60ACC018B}, Volume = {13}, Year = {2003}} @article{Bai:1996, Abstract = {The colchicine analog 3-chloroacetyl-3-demthylthio-colchicine (3CTC) is a competitive inhibitor of colchicine binding to tubulin, binds to tubulin at 37 degrees C, but not at 0 degree C, and covalently reacts with beta-tubulin at 37 degree C, but not at 0 degree C, in a reaction inhibited by colchicine site drugs. The approximate intramolecular distance between the oxygen at position C-3 in 3CTC and the chlorine atom of the 3-chloroacetyl group is 3 A. using decylagarose chromatography, we purified beta-tubulin that had reacted with 3-(chloromethyl-[14C] Carbonyl)-3- demethylthiocolchicine ([14C]3CTC). This beta-tubulin that had reacted with 3-(chloromethyl-[14C]carbonyl)- 3-demethythiocolchicine ([14C]3CTC). This beta-tubulin was digested with formic acid, cyanogen bromide, endoproteinase Glu-C, or endoproteinase Lys-C, and the radio-labeled peptide(s) were isolated. The sequences of these peptides indicated that as much as 90\%of the covalent reaction between the [14C]3CTC and beta-tubulin occurred at cysteine 354. This finding indicates that the C-3 oxygen atom of colchicinoids is within 3 A of the sulfur atom of the Cys-354 residue, suggests that the colchicine A ring lies between Cys-354 and Cys-239, based on the known 9 A distance between these residues, and may indicate that the tropolone C ring lies between the peptide region containing Cys-239 and the amino-terminal beta-tubulin sequence, based on the labeling pattern observed following direct photoactivation of tubulin-bound colchicine. 0021-9258 Journal Article}, Author = {Bai, R. and Pei, X. F. and Boye, O. and Getahun, Z. and Grover, S. and Bekisz, J. and Nguyen, N. Y. and Brossi, A. and Hamel, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Biol Chem}, Keywords = {Protein Binding;Colchicine/analogs &derivatives/antagonists &;Tubulin/chemistry/*metabolism;EE, T abstr;inhibitors/*metabolism/pharmacology;Cyanogen Bromide;Molecular Sequence Data;08 Aberrant cell cycle;Cysteine/*metabolism;Amino Acid Sequence;Cattle;Chromatography, High Pressure Liquid;Animals}, Number = {21}, Organization = {Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.}, Pages = {12639-45}, Pubmed = {8647876}, Title = {Identification of cysteine 354 of beta-tubulin as part of the binding site for the A ring of colchicine}, Uuid = {DA9F68E4-B3C8-4299-B2D2-0B9261BB6084}, Volume = {271}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8647876}} @article{Bailey:1999, Abstract = {Olfactory bulb (OB) glomeruli have long been considered functional units in the processing of odor information. Recently, it has been shown that axons from olfactory receptor neurons (ORNs) expressing the same odorant receptor gene converge onto two or a few topographically fixed glomeruli in the OB. The interactions between ORN axons, mitral/tufted cell dendrites, juxtaglomerular (JG) cells, and glial cells during the development of glomeruli is of great importance in light of this receptor gene glomerular topography in the primary olfactory projection. To explore the development of mammalian olfactory glomeruli, we investigated the relationships among radial glia (RG), astrocytes, ORNs, JG cells, mitral/tufted cell dendrites, and olfactory Schwann cells throughout embryonic and early postnatal development. Our results indicate that glomeruli are formed through an invariant sequence of cellular events: (1) pioneering ORN axons contact the rostral telencephalon at approximately E11-14, which coincides with the onset of morphologic changes in telencephalic RG; (2) at E15-16, RG branch and begin to form two plexuses, one located in the subventricular layer and the other superficial to the presumptive mitral cell layer; (3) at E17-18, ORN axons accumulate in a dense band superficial to the outer radial glia plexus; (4) at E19-20, processes from RG and astrocytes begin to ramify to form glial tufts, or glial glomeruli. Coincident with the formation of these glial glomeruli, ORN axons intermingle with the glial processes and form proto-glomeruli; (5) at E21 to P0, JG cells begin to migrate into position surrounding glomeruli, (6) and at P4, the apical tuft of mitral cells becomes restricted to a single glomerulus. Interestingly, glomerular development also occurs in a distinct rostral to caudal gradient. That is, glomeruli in the rostral OB develop earlier than those in the caudal OB, but the sequence of cellular events at any point in the bulb is invariant. These results demonstrate that glomeruli are formed in a specific spatiotemporal sequence beginning with ORN axon-glia contacts, then JG cell arrival, and finally mitral cell apical dendrite restriction.}, Author = {Bailey, M. S. and Puche, A. C. and Shipley, M. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:50 -0400}, Journal = {J Comp Neurol}, Keywords = {Embryo;I;Microtubule-Associated Proteins/analysis;Vimentin/analysis;Rats;GAP-43 Protein/analysis;Glial Fibrillary Acidic Protein/analysis;Animal;Olfactory Receptor Neurons/*cytology/*metabolism;Support, U.S. Gov't, P.H.S.;Olfactory Bulb/*cytology/*metabolism;Animals, Newborn;Support, Non-U.S. Gov't;Astrocytes/*cytology/*metabolism;13 Olfactory bulb anatomy;Nerve Tissue Proteins/analysis}, Number = {4}, Organization = {Department of Anatomy and Neurobiology, Program in Neuroscience, The University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA.}, Pages = {423-48.}, Title = {Development of the olfactory bulb: evidence for glia-neuron interactions in glomerular formation}, Uuid = {8A8A71C7-A124-4459-B771-1A0C2A00EC05}, Volume = {415}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10570454}} @article{Bakal:2007, Abstract = {Although classical genetic and biochemical approaches have identified hundreds of proteins that function in the dynamic remodeling of cell shape in response to upstream signals, there is currently little systems-level understanding of the organization and composition of signaling networks that regulate cell morphology. We have developed quantitative morphological profiling methods to systematically investigate the role of individual genes in the regulation of cell morphology in a fast, robust, and cost-efficient manner. We analyzed a compendium of quantitative morphological signatures and described the existence of local signaling networks that act to regulate cell protrusion, adhesion, and tension.}, Author = {Bakal, Chris and Aach, John and Church, George and Perrimon, Norbert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {research support, non-u.s. gov't;Phenotype;Cell Line;Metabolic Networks and Pathways;Signal Transduction;RNA Interference;Cell Shape;research support, n.i.h., extramural;Drosophila;Green Fluorescent Proteins;Animals;Cell Movement;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0404511}, Number = {5832}, Organization = {Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {1753-6}, Pii = {316/5832/1753}, Pubmed = {17588932}, Title = {Quantitative morphological signatures define local signaling networks regulating cell morphology}, Uuid = {84F51BD1-5383-42B8-950A-A49BBB4E62BB}, Volume = {316}, Year = {2007}, url = {papers/Bakal_Science2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1140324}} @article{Baker:1988, Abstract = {Peripheral deafferentation of the mouse main olfactory bulb following intranasal irrigation with ZnSO4 produced profound decreases in tyrosine hydroxylase activity and immunoreactivity in intrinsic dopamine neurons normally localized to the juxtaglomerular region of the bulb. In contrast, only modest alterations in GABA-immunoreactivity and glutamic acid decarboxylase (GAD) activity were observed in the same region. In fact, when GAD activity was expressed per mg tissue, a reflection of enzyme concentration, no changes in activity were observed 3 weeks postlesion and only relatively modest decreases in specific activity were found following long survival times (4 months). When the data were expressed per bulb, as an indication of the total amount of enzyme present, GAD activity and bulb weight exhibited similar reductions. Olfactory marker protein levels, determined as an indication of the completeness of the deafferentation, were at or below the limits of detection in all lesioned mice. These data indicate that afferent regulation of transmitter expression in the juxtaglomerular neurons of the olfactory system is phenotype specific.}, Author = {Baker, H. and Towle, A. C. and Margolis, F. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Animals;13 Olfactory bulb anatomy;Glutamate Decarboxylase;Zinc;Female;Nerve Tissue Proteins;Olfactory Marker Protein;Immunohistochemistry;Sulfates;Olfactory Bulb;gamma-Aminobutyric Acid;Afferent Pathways;Male;Mice;Dopamine;Tyrosine 3-Monooxygenase;Zinc Sulfate}, Medline = {88294657}, Month = {5}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Cornell University Medical College, New York, NY 10021.}, Pages = {69-80}, Pii = {0006-8993(88)91545-4}, Pubmed = {2900047}, Title = {Differential afferent regulation of dopaminergic and GABAergic neurons in the mouse main olfactory bulb}, Uuid = {FBEC1304-D067-11DA-8A8C-000D9346EC2A}, Volume = {450}, Year = {1988}} @article{Baker:2006, Abstract = {The MRL mouse is unique in its capacity for regenerative healing of wounds. This regenerative ability includes complete closure, with little scarring, of wounds to the ear pinna and repair of cardiac muscle, without fibrosis, following cryoinjury. Here, we examine whether neurogenic zones within the MRL brain show enhanced regenerative capacity. The largest neurogenic zone in the adult brain, the subventricular zone (SVZ), lies adjacent to the lateral wall of the lateral ventricle and is responsible for replacement of interneuron populations within the olfactory bulb. Initial gross observation of the anterior forebrain in MRL mice revealed enlarged lateral ventricles; however, little neurodegeneration was detected within the SVZ or surrounding tissues. Instead, increased proliferation within the SVZ was observed, based on incorporation of the thymidine analogue bromodeoxyuridine. Closer examination using electron microscopy revealed that a significant number of SVZ astrocytes interpolated within the ependyma and established contact with the ventricle. In addition, subependymal, protuberant nests of cells, consisting primarily of neuroblasts, were found along the anterior SVZ of MRL mice. Whole mounts of the lateral wall of the lateral ventricle stained for the neuroblast marker doublecortin revealed normal formation of chains of migratory neuroblasts along the entire wall and introduction of enhanced green fluorescent protein-tagged retrovirus into the lateral ventricles confirmed that newly generated neuroblasts were able to track into the olfactory bulb.}, Author = {Baker, Kasey L. and Daniels, Stephen B. and Lennington, Jessica B. and Lardaro, Thomas and Czap, Alexandra and Notti, Ryan Q. and Cooper, Oliver and Isacson, Ole and Frasca, Salvatore and Conover, Joanne C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Microscopy, Electron, Transmission;Neurons;02 Adult neurogenesis migration;24 Pubmed search results 2008;Wound Healing;Cell Proliferation;research support, non-u.s. gov't ;Astrocytes;Immunohistochemistry;Stem Cells;Cell Death;Animals;Brain;Cell Movement;Male;Mice}, Month = {10}, Nlm_Id = {0406041}, Number = {6}, Organization = {Center for Regenerative Biology, University of Connecticut, Storrs, 06269, USA.}, Pages = {747-61}, Pubmed = {16927265}, Title = {Neuroblast protuberances in the subventricular zone of the regenerative MRL/MpJ mouse}, Uuid = {128FCCB8-33DA-4709-949A-0B985039DF87}, Volume = {498}, Year = {2006}, url = {papers/Baker_JCompNeurol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21090}} @article{Baker:2001, Abstract = {A possible source for transplantable neurons in Parkinson's disease are adult olfactory bulb (OB) dopamine (DA) progenitors that originate in the anterior subventricular zone and reach the OB through the rostral migratory stream. We used adult transgenic mice expressing a lacZ reporter directed by an 8.9 kb tyrosine hydroxylase (TH) promoter to investigate the course of DAergic differentiation. Parallel transgene and intrinsic TH mRNA expression occurred during migration of DA interneurons through the mitral and superficial granule cell layers before these cells reached their final periglomerular position. Differential transgene and calcium-calmodulin-dependent protein kinase IV expression distinguished two nonoverlapping populations of interneurons. Transgenic mice carrying a TH8.9kb/lacZ construct with a mutant AP-1 site demonstrated that this element confers OB DA-specific TH gene regulation. These results indicate that DA phenotypic determination is specific to a subset of mobile OB progenitors.}, Author = {Baker, H. and Liu, N. and Chun, H. S. and Saino, S. and Berlin, R. and Volpe, B. and Son, J. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {J Neurosci}, Keywords = {13 Olfactory bulb anatomy;I both}, Number = {21}, Organization = {Burke Medical Research Institute, Weill Medical College, Cornell University, White Plains, New York 10605.}, Pages = {8505-13.}, Title = {Phenotypic differentiation during migration of dopaminergic progenitor cells to the olfactory bulb}, Uuid = {5F27B1F2-E14D-4C82-9606-52832F65528C}, Volume = {21}, Year = {2001}, url = {papers/Baker_JNeurosci2001.pdf}} @article{Bal:2000, Abstract = {Thalamic circuits have an intrinsic capacity to generate state-dependent oscillations of different frequency and degrees of synchrony, but little is known of how synchronized oscillation is controlled in the intact brain or what function it may serve. The influence of cortical feedback was examined using slice preparations of the visual thalamus and computational models. Cortical feedback was mimicked by stimulating corticothalamic axons, triggered by the activity of relay neurons. This artificially coupled network had the capacity to self-organize and to generate qualitatively different rhythmical activities according to the strength of corticothalamic feedback stimuli. Weak feedback (one to three shocks at 100-150 Hz) phase-locked the spontaneous spindle oscillations (6-10 Hz) in geniculate and perigeniculate nuclei. However, strong feedback (four to eight shocks at 100-150 Hz) led to a more synchronized oscillation, slower in frequency (2-4 Hz) and dependent on GABA(B) receptors. This increase in synchrony was essentially attributable to a redistribution of the timing of action potential generation in lateral geniculate nucleus cells, resulting in an increased output of relay cells toward the cortex. Corticothalamic feedback is thus capable of inducing highly synchronous slow oscillations in physiologically intact thalamic circuits. This modulation may have implications for a better understanding of the descending control of thalamic nuclei by the cortex, and the genesis of pathological rhythmical activity, such as absence seizures.}, Author = {Bal, T. and Debay, D. and Destexhe, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Electric Stimulation;Animals;Ferrets;Neural Networks (Computer);Feedback;Visual Pathways;Axons;in vitro ;Reaction Time;Receptors, AMPA;Biological Clocks;Receptors, GABA-B;research support, non-u.s. gov't ;Computer Simulation;Receptors, GABA-A;Action Potentials;Thalamus;Cerebral Cortex;Neurons;21 Neurophysiology;GABA Antagonists;21 Cortical oscillations;24 Pubmed search results 2008;Stimulation, Chemical;Geniculate Bodies;Models, Neurological;Excitatory Postsynaptic Potentials}, Month = {10}, Nlm_Id = {8102140}, Number = {19}, Organization = {Unit{\'e} de Neurosciences Int{\'e}gratives et Computationnelles, Centre National de la Recherche Scientifique, Unit{\'e} Propre de Recherche 2191, Institut de Neurobiologie A. Fessard, 91 198, Gif-sur-Yvette Cedex, France. Thierry.Bal\@iaf.cnrs-gif.fr}, Pages = {7478-88}, Pubmed = {11007907}, Title = {Cortical feedback controls the frequency and synchrony of oscillations in the visual thalamus}, Uuid = {05CE1563-3CB6-4EAC-A199-A8CAA51C76DB}, Volume = {20}, Year = {2000}} @article{Balci:2007, Abstract = {Periventricular nodular heterotopia (PNH) is a rare neuronal migration disorder in which immature neurons fail to undergo a directed migration from the ventricular and subventricular zones to the cerebral cortex. Classic PNH occurs predominantly in females and is associated with periods of epilepsy and near-normal intelligence. One gene associated with PNH was mapped to chromosome Xq28. PNH with learning disability is reported in 15 male patients with several syndromes and various congenital abnormalities such as craniosynostosis, frontonasal malformation, and agenesis of the corpus callosum. We present a 26-year-old male patient who was followed up with the diagnosis of epilepsy from the age of 1 year. Additionally the patient had severe learning disability, obesity, and hypogonadism. Imaging of his brain demonstrated PNH. Klinefelter syndrome was clinically suspected, and analysis of his chromosomes revealed a karyotype 46,XY,der(19)t(X;19) (q11.1-11.2;p13.3). Molecular techniques, such as subtelomere-specific fluorescent in-situ hybridization and multicolour banding, were also used. The same translocation was demonstrated in his mother and his maternal grandmother. This family might help to explain the gene localization of X-linked recessive PNH. In our patient, PNH is associated with familial (X;19) translocation. To our knowledge, this unique combination has not been reported in the medical literature.}, Author = {Balci, Sevim and Unal, Aysun and Engiz, Ozlem and Aktas, Dilek and Liehr, Thomas and Gross, Madelaine and Mrasek, Kristin and Saygi, Serap}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0012-1622}, Journal = {Dev Med Child Neurol}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {3}, Nlm_Id = {0006761}, Number = {3}, Organization = {Department of Clinical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Turkey.}, Pages = {219-24}, Pii = {DMCN219}, Pubmed = {17355480}, Title = {Bilateral periventricular nodular heterotopia, severe learning disability, and epilepsy in a male patient with 46,XY,der(19)t(X;19) (q11.1-11.2;p13.3)}, Uuid = {FFFFF166-7DBB-4990-874D-9603CFD4E3A1}, Volume = {49}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1469-8749.2007.00219.x}} @article{Ballas:2005, Abstract = {Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its co-repressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.}, Author = {Ballas, Nurit and Grunseich, Christopher and Lu, Diane D. and Speh, Joan C. and Mandel, Gail}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Research Support, Non-U.S. Gov't;Cell Differentiation;Animals;Genes, Regulator;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Chromatin;Neuronal Plasticity;Cells, Cultured;Nervous System;Transcription Factors;Research Support, U.S. Gov't, P.H.S.;Neurons;Pluripotent Stem Cells;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Repressor Proteins;DNA Methylation}, Month = {5}, Nlm_Id = {0413066}, Number = {4}, Organization = {Howard Hughes Medical Institute, Dept. of Neurology and Behavior, The State University of New York at Stony Brook, Stony Brook, NY 11794, USA. nballas\@notes.cc.sunysb.edu}, Pages = {645-57}, Pii = {S0092-8674(05)00285-0}, Pubmed = {15907476}, Title = {REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis}, Uuid = {147958CE-0275-455F-ABF0-61E66EF02520}, Volume = {121}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.03.013}} @article{Baltimore:1971, Author = {Baltimore, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0028-4793}, Journal = {N Engl J Med}, Keywords = {15 Retrovirus mechanism;RNA, Neoplasm;24 Pubmed search results 2008;Virus Replication;Leukemia;Oncogenic Viruses;Histocytochemistry;Cell-Free System;Humans;RNA, Viral;RNA Viruses;DNA Nucleotidyltransferases;Animals}, Medline = {71079019}, Month = {2}, Nlm_Id = {0255562}, Number = {5}, Pages = {273-5}, Pubmed = {5539352}, Title = {Reversal of information flow in the growth of RNA tumor viruses}, Uuid = {FC43FEF6-4D24-4C15-A6B2-7E166BDB1D99}, Volume = {284}, Year = {1971}} @article{Banati:1994, Abstract = {The study of microglial cell biology has become the key to understanding the brain's fundamental tissue reactions as well as the cellular mechanisms underlying CNS disease. This article focuses on glial-neuronal interactions with special reference to human pathology. Three important areas of brain pathology are critically reviewed: multiple sclerosis and CNS inflammation, the brain in AIDS and opportunistic infections, and neurodegenerative disorders. Although microglial cytotoxicity may cause bystander damage, e.g. in ischemia, there is little evidence to support the view that microglial activation per se is pathogenic. Results suggesting that one important normal function of microglia is to protect the integrity of the central nervous system are discussed. The concept is proposed that microglia function as a highly developed guardian to the CNS.}, Author = {Banati, R. B. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Central Nervous System;Inflammation;Cell Survival;11 Glia;Microglia;Animals;Humans;review}, Medline = {95220173}, Nlm_Id = {7809375}, Number = {3-4}, Organization = {Department of Neuromorphology, Max-Planck-Institute of Psychiatry, Martinsried, Germany.}, Pages = {114-27}, Pubmed = {7705219}, Title = {Surveillance, intervention and cytotoxicity: is there a protective role of microglia?}, Uuid = {5989FFDF-D935-4DD5-8B7A-9AF082EC85B9}, Volume = {16}, Year = {1994}} @article{Banfield:2003, Abstract = {The transsynaptic retrograde transport of the pseudorabies virus Bartha (PRV-Bartha) strain has become an important neuroanatomical tract-tracing technique. Recently, dual viral transneuronal labeling has been introduced by employing recombinant strains of PRV-Bartha engineered to express different reporter proteins. Dual viral transsynaptic tracing has the potential of becoming an extremely powerful method for defining connections of single neurons to multiple neural circuits in the brain. However, the present use of recombinant strains of PRV expressing different reporters that are driven by different promoters, inserted in different regions of the viral genome, and detected by different methods limits the potential of these recombinant virus strains as useful reagents. We previously constructed and characterized PRV152, a PRV-Bartha derivative that expresses the enhanced green fluorescent protein. The development of a strain isogenic to PRV152 and differing only in the fluorescent reporter would have great utility for dual transsynaptic tracing. In this report, we describe the construction, characterization, and application of strain PRV614, a PRV-Bartha derivative expressing a novel monomeric red fluorescent protein, mRFP1. In contrast to viruses expressing DsRed and DsRed2, PRV614 displayed robust fluorescence both in cell culture and in vivo following transsynaptic transport through autonomic circuits afferent to the eye. Transneuronal retrograde dual PRV labeling has the potential to be a powerful addition to the neuroanatomical tools for investigation of neuronal circuits; the use of strain PRV614 in combination with strain PRV152 will eliminate many of the pitfalls associated with the presently used pairs of PRV recombinants. 0022-538x Journal Article}, Author = {Banfield, B. W. and Kaufman, J. D. and Randall, J. A. and Pickard, G. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {J Virol}, Keywords = {Suprachiasmatic Nucleus/virology;Rats;Cell Line;Ganglia, Spinal/virology;Herpesvirus 1, Suid/*physiology;Support, U.S. Gov't, P.H.S.;15 Retrovirus mechanism;J, T pdf;Luminescent Proteins/*metabolism;Animals;Support, Non-U.S. Gov't;Synapses/*virology}, Number = {18}, Organization = {Department of Microbiology, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Campus Box B175, Denver, CO 80262, USA. bruce.banfield\@uchsc.edu}, Pages = {10106-12}, Title = {Development of pseudorabies virus strains expressing red fluorescent proteins: new tools for multisynaptic labeling applications}, Uuid = {04A30716-3DBD-41E6-B020-A9C693F8303D}, Volume = {77}, Year = {2003}, url = {papers/Banfield_JVirol2003.pdf}} @article{Bannert:2004, Abstract = {Retroelements constitute a large portion of our genomes. One class of these elements, the human endogenous retroviruses (HERVs), is comprised of remnants of ancient exogenous retroviruses that have gained access to the germ line. After integration, most proviruses have been the subject of numerous amplifications and have suffered extensive deletions and mutations. Nevertheless, HERV-derived transcripts and proteins have been detected in healthy and diseased human tissues, and HERV-K, the youngest, most conserved family, is able to form virus-like particles. Although it is generally accepted that the integration of retroelements can cause significant harm by disrupting or disregulating essential genes, the role of HERV expression in the etiology of malignancies and autoimmune and neurologic diseases remains controversial. In recent years, striking evidence has accumulated indicating that some proviral sequences and HERV proteins might even serve the needs of the host and are therefore under positive selection. The remarkable progress in the analysis of host genomes has brought to light the significant impact of HERVs and other retroelements on genetic variation, genome evolution, and gene regulation.}, Author = {Bannert, Norbert and Kurth, Reinhard}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {15 ERVs retroelements;Endogenous Retroviruses;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Retroviridae Proteins;Microscopy, Electron;Evolution, Molecular;Genome, Human;Gene Expression;15 Retrovirus mechanism;Humans;Antibodies, Viral;Retroelements;Proviruses;review}, Month = {10}, Nlm_Id = {7505876}, Organization = {Robert Koch-Institut, Nordufer 20, 13353 Berlin, Germany. bannertn\@rki.de}, Pages = {14572-9}, Pii = {0404838101}, Pubmed = {15310846}, Title = {Retroelements and the human genome: new perspectives on an old relation}, Uuid = {C65C30C1-EE4E-11DA-8605-000D9346EC2A}, Volume = {101 Suppl 2}, Year = {2004}, url = {papers/Bannert_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0404838101}} @article{Bansal:2000, Abstract = {Before phototransduction, spontaneous activity in the developing mammalian retina is required for the appropriate patterning of retinothalamic connections, and there is growing evidence that this activity influences the development of circuits within the retina itself. We demonstrate here that the neural substrate that generates waves in the mouse retina develops through three distinct stages. First, between embryonic day 16 and birth [postnatal day 0 (P0)], we observed both large, propagating waves inhibited by nicotinic acetylcholine receptor (nAChR) antagonists and small clusters of cells displaying nonpropagating, correlated calcium increases that were independent of nAChR activation. Second, between P0 and P11, we observed only larger propagating waves that were abolished by toxins specific to alpha3 and beta2 subunit-containing nAChRs. Third, between P11 and P14 (eye opening) we observed propagating activity that was abolished by ionotropic glutamate receptor antagonists. The time course of this developmental shift was dramatically altered in retinas from mice lacking the beta2 nAChR subunit or the beta2 and beta4 subunits. These retinas exhibited a novel circuit at P0, no spontaneous correlated activity between P1 and P8, and the premature induction at P8 of an ionotropic glutamate receptor-based circuit. Retinas from postnatal mice lacking the alpha3 nAChR subunit exhibited spontaneous, correlated activity patterns that were similar to those observed in embryonic wild-type mice. In alpha3-/- and beta2-/- mice, the development and distribution of cholinergic neurons and processes and the density of retinal ganglion cells (RGCs) and the gross segregation of their dendrites into ON and OFF sublaminae were normal. However, the refinement of individual RGC dendrites is delayed. These results indicate that retinal waves mediated by nAChRs are involved in, but not required for, the development of neural circuits that define the ON and OFF sublamina of the inner plexiform layer.}, Author = {Bansal, A. and Singer, J. H. and Hwang, B. J. and Xu, W. and Beaudet, A. and Feller, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-07-31 18:57:07 +0000}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Retina;Fluorescent Dyes;Cell Differentiation;Protein Subunits;Animals;in vitro;Receptors, Glutamate;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Patch-Clamp Techniques;in vitro ;Reaction Time;Mice, Inbred C57BL;Biological Clocks;research support, non-u.s. gov't;Choline O-Acetyltransferase;Calcium;Dendrites;research support, non-u.s. gov't ;Action Potentials;Mice, Knockout;21 Neurophysiology;Nicotinic Antagonists;research support, u.s. gov't, p.h.s.;Mice;21 Cortical oscillations;24 Pubmed search results 2008;Receptors, Nicotinic;Retinal Ganglion Cells; retinal waves; currOpinRvw}, Month = {10}, Nlm_Id = {8102140}, Number = {20}, Organization = {Synapse Formation and Function Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda, Maryland, USA.}, Pages = {7672-81}, Pii = {20/20/7672}, Pubmed = {11027228}, Title = {Mice lacking specific nicotinic acetylcholine receptor subunits exhibit dramatically altered spontaneous activity patterns and reveal a limited role for retinal waves in forming ON and OFF circuits in the inner retina}, Uuid = {A9B23576-4C32-4166-A52E-23A59C724AE0}, Volume = {20}, Year = {2000}, url = {papers/Bansal_JNeurosci2000.pdf}} @article{Baraban:1995, Abstract = {Prenatal methylazoxymethanol acetate (MAMac) injection disrupts cell migration in developing rats. We investigated the electrophysiological characteristics of hippocampal CA1 pyramidal neurons from young MAMac-treated animals (postnatal days 25-35). In vitro intracellular recordings from CA1 cells in MAMac-treated tissue revealed resting membrane potential (mean, -61.5 +/- 1.5 mV), action potential amplitude (mean, 69 +/- 3.1 mV), action potential duration (mean, 2.1 +/- 0.2 ms), input resistance (mean, 51.5 +/- 3.6 M omega) and time constant (mean, 33.2 +/- 1.2 ms) similar to those of CA1 cells from control tissue. However, MAMac-treated tissue could be distinguished as having a higher percentage of cells (62\%vs. 10\%) which fire a burst of action potentials in response to suprathreshold current injection. The synaptic responses of CA1 cells in MAMac-treated and control tissue were comparable. The CA1 field response to stimulation was also comparable at all stimulus intensities tested (50-1500 microA). Elevation of extracellular potassium concentration ([K+]o) from 3 mM to 6 mM resulted in epileptiform discharge activity in response to stratum radiatum stimulation in all MAMac-treated slices (10/10) but in only one-third of controls (3/9). Spontaneous epileptiform discharges were also observed in the majority (8/13) of MAMac-treated slices bathed in 6 mM KCl but in no controls. These data suggest that MAMac treatment during fetal development not only disrupts normal anatomical organization but also leads to alterations in electrophysiological features of the hippocampal CA1 pyramidal cell region. As such, the MAMac model may provide insights into early onset seizure syndromes associated with developmental abnormalities.}, Author = {Baraban, S. C. and Schwartzkroin, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Pregnancy;Animals;Synapses;Evoked Potentials;Rats;21 Epilepsy;Female;Cell Movement;Rats, Sprague-Dawley;Microcephaly;21 Dysplasia-heterotopia;Pyramidal Cells;Potassium Chloride;Male;Action Potentials;21 Neurophysiology;Methylazoxymethanol Acetate;24 Pubmed search results 2008}, Medline = {96274902}, Month = {10}, Nlm_Id = {8703089}, Number = {2}, Organization = {Department of Neurological Surgery, University of Washington, Seattle 98195, USA.}, Pages = {145-56}, Pii = {0920121195000453}, Pubmed = {8777901}, Title = {Electrophysiology of CA1 pyramidal neurons in an animal model of neuronal migration disorders: prenatal methylazoxymethanol treatment}, Uuid = {CD72D2E1-0156-11DB-9E68-000D9346EC2A}, Volume = {22}, Year = {1995}, url = {papers/Baraban_EpilepsyRes1995.pdf}} @article{Baraban:1996, Abstract = {Methylazoxymethanol acetate (MAMac) is a potent teratogenic agent which can produce ectopic cell placement in developing rat brains. In the present study, we evaluated (i) whether prenatal exposure to MAMac results in a lowered seizure threshold to flurothyl and (ii) if there is a correlation between the number of ectopic cells in MAMac-exposed hippocampus and flurothyl-induced seizure latency. In 60 day old (P60) rats exposed to MAMac in utero, the latencies to myoclonic jerk (173 +/- 2.3 s) and forelimb clonus (215 +/- 4.6 s) were significantly shorter than those of controls (200 +/- 6.9 s and 238 +/- 8.8 s, respectively). MAMac also increased the proportion of flurothyl-treated rats that progressed from bilateral forelimb clonus to generalized tonic-clonic seizures (control: 33\%; MAMac: 91\%). Shorter seizure latencies were associated with an increased number of ectopic pyramidal cells in region CA1/CA2. These results suggest seizure susceptibility is enhanced in an animal model (MAMac) characterized by abnormal neuronal migration.}, Author = {Baraban, S. C. and Schwartzkroin, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:35:04 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {10 Development;Pregnancy;Animals;Rats;Seizures;Myoclonus;Female;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Male;Teratogens;10 genetics malformation;Methylazoxymethanol Acetate;Epilepsy, Tonic-Clonic;Convulsants;Mice;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Flurothyl}, Month = {4}, Nlm_Id = {8703089}, Number = {3}, Organization = {Department of Neurological Surgery/Physiology, University of Washington, Seattle 98195, USA. bara\@tt.washington.edu}, Pages = {189-94}, Pii = {0920121195000941}, Pubmed = {8739122}, Title = {Flurothyl seizure susceptibility in rats following prenatal methylazoxymethanol treatment}, Uuid = {3FEB1774-8A61-42D0-9384-AE2B40D97887}, Volume = {23}, Year = {1996}, url = {papers/Baraban_EpilepsyRes1996.pdf}} @article{Baraban:2000, Abstract = {Cortical disorganization represents one of the major clinical findings in many children with medically intractable epilepsy. To study the relationship between seizure propensity and abnormal cortical structure, we have begun to characterize an animal model exhibiting aberrant neuronal clusters (heterotopia) and disruption of cortical lamination. In this model, exposing rats in utero to the DNA methylating agent methylazoxymethanol acetate (MAM; embryonic day 15) disrupts the sequence of normal brain development. In MAM-exposed rats, cells in hippocampal heterotopia exhibit neuronal morphology and do not stain with immunohistochemical markers for glia. In hippocampal slices from MAM-exposed animals, extracellular field recordings within heterotopia suggest that these dysplastic cell clusters make synaptic connections locally (i.e. within the CA1 hippocampal subregion) and also make aberrant synaptic contact with neocortical cells. Slice perfusion with bicuculline or 4-aminopyridine leads to epileptiform activity in dysplastic cell clusters that can occur independent of input from CA3. Taken together, our findings suggest that neurons within regions of abnormal hippocampal organization are capable of independent epileptiform activity generation, and can project abnormal discharge to a broad area of neocortex, as well as hippocampus.}, Author = {Baraban, S. C. and Wenzel, H. J. and Hochman, D. W. and Schwartzkroin, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Pregnancy;Electrophysiology;Animals;Synapses;Rats;21 Epilepsy;Female;Epilepsy;Rats, Sprague-Dawley;Hippocampus;Brain Diseases;Bicuculline;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Methylazoxymethanol Acetate;Convulsants;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;4-Aminopyridine;Choristoma;Research Support, Non-U.S. Gov't}, Medline = {20221047}, Month = {4}, Nlm_Id = {8703089}, Number = {2}, Organization = {Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106, USA. baraban\@itsa.ucsf.edu}, Pages = {87-102}, Pii = {S0920121199001047}, Pubmed = {10759297}, Title = {Characterization of heterotopic cell clusters in the hippocampus of rats exposed to methylazoxymethanol in utero}, Uuid = {C0B26BF7-F1F2-48EB-903C-19B689F2551F}, Volume = {39}, Year = {2000}} @article{Baraban:1997, Abstract = {A variety of neurological complications has been reported in infants exposed to cocaine during gestation. In the present study, intrinsic cell properties of hippocampal neurons from CA1, CA3, and dentate gyrus regions were measured and compared in tissue from neonatal rats exposed to saline or cocaine in utero. Synaptic properties of the CA1 pyramidal cell region were analyzed at postnatal day (P) 20 with the use of extracellular and intracellular recording techniques. In vitro intracellular recordings (n = 223) obtained at P10, P15 and P20 in tissue from cocaine- and saline-exposed animals revealed no differences in standard cell properties such as resting membrane potential, input resistance, time constant, and action potential amplitude or duration. Hippocampal slices from cocaine-exposed animals exhibited a marked reduction of spike frequency adaptation for all three types of principal hippocampal neurons (e.g., CA1, CA3, and granule cells). The amplitudes of afterhyperpolarizations following a spike train were also decreased in CA1 and CA3 cells in tissue from cocaine-exposed animals. Extracellular and intracellular recordings in the CA1 pyramidal cell region at P20 were obtained to assess and compare synaptic function in tissue from cocaine- and saline-exposed animals. In hippocampal slices from cocaine-exposed animals, synaptic responses in the CA1 region were characterized by multiple population spike activity and reduced inhibitory postsynaptic potentials. The reduction in fast inhibitory postsynaptic potential conductance was not associated with a change in reversal potential. These results suggest that gestational cocaine exposure induces significant changes in intrinsic and synaptic electrophysiological properties of hippocampal neurons in the developing animal. The cell and synaptic features are consistent with an increase in hippocampal excitability, which may contribute to the neurobehavioral deficits and epileptogenic predisposition reported in this infant population. As such, this in utero drug exposure model may provide a useful system in which to elucidate and study the basic cellular mechanisms underlying neurological complications associated with maternal cocaine abuse.}, Author = {Baraban, S. C. and Schwartzkroin, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Narcotics;Pregnancy;Electrophysiology;Animals;Synapses;In Vitro;Aging;Rats;21 Epilepsy;Female;Extracellular Space;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Membrane Potentials;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Cocaine;Research Support, Non-U.S. Gov't}, Medline = {97171309}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Neurological Surgery, University of Washington, Seattle 98195, USA.}, Pages = {126-36}, Pubmed = {9120553}, Title = {Effects of prenatal cocaine exposure on the developing hippocampus: intrinsic and synaptic physiology}, Uuid = {61DA9708-B85C-4D26-AB6C-35150D37143D}, Volume = {77}, Year = {1997}, url = {papers/Baraban_JNeurophysiol1997.pdf}} @article{Barinaga:2003, Abstract = {1095-9203 Comment News}, Author = {Barinaga, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Science}, Keywords = {Cell Survival;Neurons/*physiology;Cell Differentiation;Human;Pregnancy;Olfactory Bulb/cytology/physiology;Animals;Rats;Memory;Stem Cells/physiology;Prolactin/*physiology;Female;Receptors, Prolactin/genetics/physiology;Brain/cytology/*physiology;Seasons;Male;Vocalization, Animal;Odors;01 Adult neurogenesis general;A;Dentate Gyrus/cytology/*physiology;Smell;*Learning;Songbirds/physiology;Mice;Cell Division}, Number = {5603}, Pages = {32-4}, Pubmed = {12511626}, Title = {Developmental biology. Newborn neurons search for meaning}, Uuid = {F5C8F045-5D06-40A9-A504-B17FFECDBA5A}, Volume = {299}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12511626}} @article{Barker:1996, Abstract = {Grafts of embryonic ventral mesencephalic tissue placed in the striatum of 6-hydroxydopamine-lesioned rats survive, and make and receive connections to and from the host brain. The dopaminergic neurons of the graft can grow processes into the host brain, and thereby alleviate many of the behavioral deficits of this form of experimental Parkinson's disease. However, when examined some weeks after implantation, grafted substantia nigra only contains about 5\%of the expected complement of dopaminergic neurons. We have examined the time course of loss of grafted neurons. We find that the majority die during the first 7 days after transplantation. However, we have shown previously that three-dimensional cultures with the same dimensions as a graft, made of identical cell suspensions, have much better dopaminergic neuronal survival. There must, therefore, be features in the environment surrounding a graft that are toxic to dopaminergic neurons. A limiting factor in the efficacy of dopaminergic grafts is the small distance over which the neurons are able to grow neurites and form connections in the host brain. We find that the growth of neurites from dopaminergic neurons into the host striatum occurs in two phases. Neurites reach their maximum length within 7 days of transplantation, and this is followed by a much slower process of branch and terminal formation. Since axon growth in the adult brain may be inhibited by a number of factors associated with reactive gliosis, we have immunostained various ages of graft for vimentin, tenascin, chondroitin sulfate proteoglycan (CS-PG) using the CS56 antibody, the DSD-1 proteoglycan, and microglia using the OX-42 antibody. We have compared this staining with that surrounding a simple stab wound. Vimentin staining was initially seen in the graft and in astrocytes immediately surrounding it. By 7 weeks staining was restricted to a ring of astrocytes surrounding the graft. Tenascin, DSD-1, and CS-PG were initially seen in and around the grafts. By 7 weeks they had disappeared from grafts, but CS-PG and tenascin persisted in small amounts around stab wounds. In general, immunostaining of these molecules persisted longer around a stab lesion than around a graft. There was also an intense local microglial reaction surrounding both grafts and stab wounds which had largely resolved by 7 weeks.}, Author = {Barker, R. A. and Dunnett, S. B. and Faissner, A. and Fawcett, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Dopamine;Animals;Corpus Striatum;Rats;review, tutorial;review;Female;Vimentin;Rats, Sprague-Dawley;Substantia Nigra;11 Glia;Fetal Tissue Transplantation;Time Factors;Support, Non-U.S. Gov't;Neurons;Tyrosine 3-Monooxygenase;Gliosis;Immunohistochemistry;Biological Markers;Cell Death}, Medline = {96390697}, Month = {9}, Nlm_Id = {0370712}, Number = {1}, Organization = {MRC Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom.}, Pages = {79-93}, Pii = {S0014488696901417}, Pubmed = {8797670}, Title = {The time course of loss of dopaminergic neurons and the gliotic reaction surrounding grafts of embryonic mesencephalon to the striatum}, Uuid = {8570C54A-5A0B-4C76-873E-8A3395966092}, Volume = {141}, Year = {1996}} @article{Barker:2005, Abstract = {Postnatal hippocampal neurogenesis in wild mammals may play an essential role in spatial memory. We compared two species that differ in their reliance on memory to locate stored food. Yellow-pine chipmunks use a single cache to store winter food; eastern gray squirrels use multiple storage sites. Gray squirrels had three times the density of proliferating cells in the dentate gyrus (determined by Ki-67 immunostaining) than that found in chipmunks, but similar density of young neurons (determined by doublecortin immunostaining). Three explanations may account for these results. First, the larger population of young cells in squirrels may increase the flexibility of the spatial memory system by providing a larger pool of cells from which new neurons can be recruited. Second, squirrels may have a more rapid cell turnover rate. Third, many young cells in the squirrels may mature into glia rather than neurons. The densities of young neurons were higher in juveniles than in adults of both species. The relationship between adult age and cell density was more complex than that has been found in captive populations. In adult squirrels, the density of proliferating cells decreased exponentially with age, whereas in adult chipmunks the density of young neurons decreased exponentially with age.}, Author = {Barker, J. M. and Wojtowicz, J. M. and Boonstra, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1601-1848}, Journal = {Genes Brain Behav}, Keywords = {01 Adult neurogenesis general;06 Adult neurogenesis injury induced;delete_this;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {101129617}, Number = {2}, Organization = {Centre for the Neurobiology of Stress, Department of Physiology, and Centre for the Neurobiology of Stress, University of Toronto, Scarborough, Ontario, Canada.}, Pages = {89-98}, Pii = {GBB097}, Pubmed = {15720405}, Title = {Where's my dinner? Adult neurogenesis in free-living food-storing rodents}, Uuid = {4D8F4EAC-6ED3-4478-AB1D-3192600984FE}, Volume = {4}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1601-183X.2004.00097.x}} @article{Barkovich:1994, Abstract = {The "band heterotopia" or "double cortex" is a brain anomaly that is presumed to result from a premature arrest of neuronal migration. Patients with this anomaly are reported to have a variable clinical course that has been, heretofore, unpredictable. The clinical records and magnetic resonance (MR) imaging studies of 27 patients with band heterotopia were retrospectively reviewed in an attempt to determine whether imaging findings are useful in predicting clinical outcome of affected patients. Statistical analyses revealed the following correlations: (1) severity of T2 prolongation in the brain with motor delay (p = 0.03); (2) degree of ventricular enlargement with the age of seizure onset (p = 0.04), and with development and intelligence (p = 0.04); (3) severity of pachygyria with the age of seizure onset (p = 0.01), seizure type (p = 0.03), and an abnormal neurologic examination (p = 0.002); (4) parietal involvement with delayed speech development (p = 0.05); (5) occipital involvement with age of seizure onset (p = 0.006); (6) age of seizure onset with development and intelligence (p = 0.03) and with an abnormal neurologic examination (p = 0.04); and (7) severity of the pachygyria and thickness of band with development of symptomatic generalized epilepsy (p = 0.002 and p = 0.02, respectively) and Lennox-Gastaut syndrome (p = 0.002 and p = 0.01, respectively).}, Author = {Barkovich, A. J. and Guerrini, R. and Battaglia, G. and Kalifa, G. and N'Guyen, T. and Parmeggiani, A. and Santucci, M. and Giovanardi-Rossi, P. and Granata, T. and D'Incerti, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {10 Development;Language Development Disorders;Magnetic Resonance Imaging;Motor Activity;Child, Preschool;Humans;Female;Epilepsy;Infant;Child;Brain Diseases;Male;Intelligence;Developmental Disabilities;10 genetics malformation;Cerebral Cortex;Infant, Newborn;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {7707449}, Number = {4}, Organization = {Neuroradiology Section, University of California, San Francisco 94143-0628.}, Pages = {609-17}, Pubmed = {7524438}, Title = {Band heterotopia: correlation of outcome with magnetic resonance imaging parameters}, Uuid = {D3C3EBD5-AB59-46EC-9FDC-EB9961248BA9}, Volume = {36}, Year = {1994}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.410360409}} @article{Barkovich:1996, Abstract = {Neuroimaging is playing an increasingly important role in the evaluation of patients with malformations of cerebral cortical development. In this review, the authors address optimal neuroimaging of cortical malformations using x-ray computed tomography, single-photon-emission computed tomography, positron emission tomography, magnetic resonance imaging, and magnetic resonance spectroscopy. Initially, the authors discuss the strengths and weaknesses of the various imaging techniques. This is followed by a discussion of the clinical and neuroimaging characteristics of several different imaging manifestations of focal malformations of cortical development, including polymicrogyria, focal subcortical heterotopia, schizencephaly, focally thickened gyri, focally irregular gyri, hemimegalencephaly, and transmural dysplasia. The authors intend that, after reading this review, the reader will have a better understanding of the optimal neuroimaging techniques for evaluating these malformations and their many neuroimaging appearances.}, Author = {Barkovich, A. J. and Kuzniecky, R. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0736-0258}, Journal = {J Clin Neurophysiol}, Keywords = {10 Development;Magnetic Resonance Imaging;Tomography, X-Ray Computed;10 genetics malformation;Tomography, Emission-Computed, Single-Photon;Humans;Tomography, Emission-Computed;Cerebral Cortex;review;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8506708}, Number = {6}, Organization = {Neuroradiology Section, University of California, San Francisco, 94143-0628, USA.}, Pages = {481-94}, Pubmed = {8978620}, Title = {Neuroimaging of focal malformations of cortical development}, Uuid = {28B43954-CB21-4A9B-AD33-DDFB8330646D}, Volume = {13}, Year = {1996}} @article{Barkovich:1996a, Abstract = {Malformations of the cerebral cortex are being recognized more frequently as a cause of epilepsy, developmental delay, neurological deficits, and mental retardation. Nonetheless, a standard nomenclature and classification system of these malformations, based upon state-of-the art knowledge derived from genetics, embryology, imaging, and pathology, has not been devised. In this manuscript, we propose such a classification system. Moreover, we have constructed the system such that both the framework and the classifications themselves are flexible and can be adapted as our knowledge of the embryology, genetics, imaging, and pathology of these disorders advances. We believe that the use of this classification system will help both clinicians and researchers to understand and think about these disorders and their causes better. In turn, we hope that this improved understanding will lead to further refinements in classification, to advances in our knowledge and, ultimately, to improvements in therapy.}, Author = {Barkovich, A. J. and Kuzniecky, R. I. and Dobyns, W. B. and Jackson, G. D. and Becker, L. E. and Evrard, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0174-304X}, Journal = {Neuropediatrics}, Keywords = {Prognosis;24 Pubmed search results 2008;Chromosome Aberrations;10 Development;Infant;Chromosome Disorders;Diagnostic Imaging;10 genetics malformation;Congenital Abnormalities;Brain Damage, Chronic;Terminology as Topic;Humans;Cerebral Cortex;review;Infant, Newborn}, Month = {4}, Nlm_Id = {8101187}, Number = {2}, Organization = {Department of Radiology, University of California San Francisco, USA.}, Pages = {59-63}, Pubmed = {8737819}, Title = {A classification scheme for malformations of cortical development}, Uuid = {6AFFA85D-FFCD-46AB-A84D-9DB7102B46F7}, Volume = {27}, Year = {1996}} @article{Barkovich:1989, Abstract = {Five patients with a continuous band of heterotopic neurons between the lateral ventricles and the cerebral cortex are described. All patients presented with intractable seizures and moderate-to-severe developmental delay. The identification of this anomaly is difficult because of its symmetry and the minimal abnormality of the gyral pattern of the cortex. The possible embryogenesis of the anomaly is discussed. The identification of these band heterotopias is important because of the intractable nature of the seizure disorder and the poor prognosis for the patient.}, Author = {Barkovich, A. J. and Jackson, D. E. and Boyer, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0033-8419}, Journal = {Radiology}, Keywords = {10 Development;Magnetic Resonance Imaging;Humans;Seizures;comparative study;Female;Child;Cell Movement;Tomography, X-Ray Computed;Brain Neoplasms;Male;Cerebral Ventricles;Developmental Disabilities;10 genetics malformation;Neurons;Cerebral Cortex;24 Pubmed search results 2008;Choristoma}, Month = {5}, Nlm_Id = {0401260}, Number = {2}, Organization = {Department of Radiology, Letterman Army Medical Center, Presidio of San Francisco.}, Pages = {455-8}, Pubmed = {2468173}, Title = {Band heterotopias: a newly recognized neuronal migration anomaly}, Uuid = {287C38FC-1597-4F27-8B3F-A8EB4F19C69A}, Volume = {171}, Year = {1989}} @article{Barkovich:1992, Abstract = {Magnetic resonance (MR) images and clinical records of 20 patients with gray matter heterotopias were retrospectively reviewed to correlate MR characteristics of the heterotopias with clinical findings. On the basis of the MR images, patients were divided into three groups: those with subependymal heterotopias (eight patients), focal subcortical gray matter heterotopias (six patients), and diffuse subcortical heterotopias (six patients). Patients with subependymal heterotopias had a significantly higher prevalence of normal development than patients in the other two groups (P = .02). When all patients with gray matter heterotopias were considered, patients with thick heterotopias and those with overlying cortical gyral anomalies, which correlated with one another, had a significantly higher prevalence of developmental delay (P = .002). Patients with thick focal gray matter heterotopias had a substantially increased prevalence of motor dysfunction. In three cases, gray matter heterotopias were associated with infoldings of dysplastic cortex containing blood vessels or cerebrospinal fluid. If not properly analyzed, these anomalies can be mistaken for vascular or cystic tumors.}, Author = {Barkovich, A. J. and Kjos, B. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0033-8419}, Journal = {Radiology}, Keywords = {10 Development;Magnetic Resonance Imaging;Child, Preschool;Humans;Seizures;Middle Aged;Paralysis;Brain;Child;Infant;Brain Neoplasms;Speech;Neurologic Examination;Intelligence;10 genetics malformation;Retrospective Studies;Cognition;Adult;Psychomotor Performance;24 Pubmed search results 2008;Choristoma;Adolescent}, Month = {2}, Nlm_Id = {0401260}, Number = {2}, Organization = {Department of Radiology, University of California, San Francisco 94143-0628.}, Pages = {493-9}, Pubmed = {1732969}, Title = {Gray matter heterotopias: MR characteristics and correlation with developmental and neurologic manifestations}, Uuid = {76311E45-AFDE-452F-BE73-F07D9E52B530}, Volume = {182}, Year = {1992}} @article{Barna:2000, Abstract = {The effect of GYKI-52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine), a selective antagonist of AMPA receptor was investigated on the generation and manifestation of 4-aminopyridine-induced cortical epileptiform activity. In vivo experiments were carried out on pentobarbital-anaesthetised adult rats. Ictal epileptiform activity was induced by local application of 4-aminopyridine (4-Ap) to the surface of somatosensory cortex. In one group of animals, GYKI 52466 was administered intraperitoneally before 4-Ap application, in another group, the already active primary focus was treated locally by GYKI 52466. Different parameters of epileptic activity were measured and compared in GYKI 52466-treated and control animals. The results demonstrate that GYKI 52466 exerts anticonvulsive effects on both the induction and the expression of epileptiform activity, by delaying the onset of the first ictal event, decreasing the numbers and duration of ictal periods, as well as the amplitudes of epileptiform discharges both in the primary and mirror foci. However, seizure propagation to other cortical areas seemed to be facilitated. The anticonvulsive effect of GYKI 52466 was stronger in pretreatment than in treatment of ongoing epileptiform activity. As a conclusion, it is supposed that AMPA receptors are probably more dominant in the induction of epileptiform activity than in the maintenance of it, mainly through the activation of corticothalamo-cortical networks. It is also supposed that the cortical inhibition which blocks the propagation of epileptiform process might be activated mainly through non-N-methyl-D-aspartate receptors.}, Author = {Barna, B. and Sz{\'a}sz, A. and Vil{\'a}gi, I. and Szente, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0361-9230}, Journal = {Brain Res Bull}, Keywords = {Anti-Anxiety Agents;Anticonvulsants;Animals;Rats;21 Epilepsy;Female;Epilepsy;Receptors, AMPA;Rats, Wistar;Time Factors;Male;Cerebral Cortex;21 Neurophysiology;4-Aminopyridine;24 Pubmed search results 2008;Electroencephalography;Benzodiazepines;Research Support, Non-U.S. Gov't}, Medline = {20181444}, Month = {2}, Nlm_Id = {7605818}, Number = {3}, Organization = {Department of Comparative Physiology, J{\'o}zsef Attila University, Szged, Hungary.}, Pages = {241-8}, Pii = {S0361923099002245}, Pubmed = {10718516}, Title = {Anticonvulsive effect of AMPA receptor antagonist GYKI 52466 on 4-aminopyridine-induced cortical ictal activity in rat}, Uuid = {AF62FE40-367E-4C62-AE5E-B96C8E871253}, Volume = {51}, Year = {2000}} @article{Barnea:2004, Author = {Barnea, G. and O'Donnell, S. and Mancia, F. and Sun, X. and Nemes, A. and Mendelsohn, M. and Axel, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:41 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Olfactory Mucosa;13 Olfactory bulb anatomy;Recombinant Fusion Proteins;Dendrites;Immunoblotting;Immunohistochemistry;Olfactory Receptor Neurons;Olfactory Bulb;Gene Targeting;Animals;Support, Non-U.S. Gov't;Mice;Receptors, Odorant;Axons}, Month = {6}, Nlm_Id = {0404511}, Number = {5676}, Organization = {Center for Neurobiology and Behavior, Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, 701 West 168th Street, New York, NY 10032, USA.}, Pages = {1468}, Pii = {304/5676/1468}, Pubmed = {15178793}, Title = {Odorant receptors on axon termini in the brain}, Uuid = {2897EA0B-7456-4997-A3D9-BC5236579D49}, Volume = {304}, Year = {2004}, url = {papers/Barnea_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1096146}} @article{Barral-Moran:2003, Abstract = {Injury to the nervous system results in reactive astrogliosis that is a critical determinant of neuronal regeneration. To analyze glial responses to mechanical injury and the role of the polysialic neural cell adhesion molecule (PSA-NCAM) in this process, we established primary glia cultures from newborn rat cerebral cortex. Scratching a confluent monolayer of primary glial cells resulted in two major events: rapid migration of oligodendrocyte progenitor-like (O-2A) cells into the wounded area and development of polarized morphology of type 1 astrocytes at the wound edge. Migrating O-2A progenitors had a bipolar morphology and exhibited A2B5 and O4 immunolabeling. Once these cells were established inside the wounded area, they lost A2B5 immunoreactivity and differentiated into glial fibrillary acidic protein-positive astrocytes. Migrating O-2A cells expressed PSA-NCAM, but type 1 astrocytes at the wound edge did not. Treatment of wounded cultures with Endo-N, which specifically removes PSA from the surface of cells, resulted in a significant decrease in O-2A cell migration into the wounded area and completely blocked the wound closure. Video time-lapse analysis showed that, in the presence of Endo-N, O-2A cells remained motile and migrated short distances but did not move away from the monolayer. These results demonstrate that O-2A progenitors contribute to reactive astrogliosis in culture and that PSA-NCAM is involved in this process by regulating cell migration.}, Author = {Barral-Moran, M-J J. and Calaora, V. and Vutskits, L. and Wang, C. and Zhang, H. and Durbec, P. and Rougon, G. and Kiss, J. Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Oligodendroglia;24 Pubmed search results 2008;Rats, Sprague-Dawley;Neuroglia;Research Support, Non-U.S. Gov't;Rats;Neural Cell Adhesion Molecule L1;Gliosis;Stem Cells;Cells, Cultured;Cell Movement;Cerebral Cortex;Animals;Sialic Acids}, Medline = {22658406}, Month = {6}, Nlm_Id = {7600111}, Number = {6}, Organization = {Departamento de Ciencias Morfologicas, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain.}, Pages = {679-90}, Pubmed = {12774308}, Title = {Oligodendrocyte progenitor migration in response to injury of glial monolayers requires the polysialic neural cell-adhesion molecule}, Uuid = {C3CF6E92-7EC6-47A3-B8A5-13D6E448624E}, Volume = {72}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10627}} @article{Barres:1999, Author = {Barres, B. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cell}, Keywords = {02 Adult neurogenesis migration;Cell Differentiation;03 Adult neurogenesis progenitor source;Human;Neuroglia/*cytology;Animal;Neurons/*cytology;Brain/*cytology;BB abstr;Stem Cells/*cytology}, Number = {6}, Organization = {Stanford University School of Medicine, Department of Neurobiology, California 94305-5125, USA.}, Pages = {667-70.}, Title = {A new role for glia: generation of neurons!}, Uuid = {8250E315-FE6F-45FD-985C-1F6372B3312A}, Volume = {97}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10380916}} @article{Barrett:1999, Author = {Barrett, L. B. and Logan, A. and Berry, M. and Ying, W. and Gonzalez, A. M. and Baird, A. and Seymour, L. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0300-5127}, Journal = {Biochem Soc Trans}, Keywords = {Hamsters;Cholera Toxin;Animals;Gene Targeting;Polylysine;Rats;Transfection;Nervous System Diseases;11 Glia;PC12 Cells;Green Fluorescent Proteins;Genetic Vectors;Cell Line;Gene Therapy;DNA, Recombinant;Neurons;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {20288925}, Month = {12}, Nlm_Id = {7506897}, Number = {6}, Organization = {CRC Institute for Cancer Studies, University of Birmingham, Edgbaston, U.K.}, Pages = {851-7}, Pubmed = {10830116}, Title = {Targeted transfection of neuronal cells using a poly(D-lysine)-cholera-toxin b chain conjugate}, Uuid = {2C7109A5-7244-4207-9C67-21DE14D57DA6}, Volume = {27}, Year = {1999}} @article{Barrette:2000, Abstract = {The low levels of transduction of human hematopoietic stem cells (HSCs) with Moloney murine leukemia virus (MLV) vectors have been an obstacle to gene therapy for hematopoietic diseases. It has been demonstrated that lentivirus vectors are more efficient than MLV vectors at transducing nondividing cell lines as well as human CD34(+) cells and severe combined immunodeficiency disease repopulating cells. We compared transduction of cell lines and Lin(-) bone marrow cells, using a vesicular stomatitis virus G (VSV-G)-pseudotyped lentivirus or MLV vectors carrying a green fluorescent protein marker gene. As predicted, the lentivirus vector was more efficient at transducing mouse and human growth-inhibited cell lines. The transduction of mouse HSC by lentivirus vectors was compared directly to MLV vectors in a co-transduction assay. In this assay, transduction by ecotropic MLV is a positive internal control for downstream steps in retrovirus transduction, including cell division. Both the VSV-G lentivirus and MLV vectors transduced mouse HSCs maintained in cytokine-free medium at very low frequency, as did the ecotropic control. The lentivirus vector and the MLV vector were equally efficient at transducing bone marrow HSCs cultured in interleukin 3 (IL-3), IL-6, and stem cell factor for 96 hours. In conclusion, although lentivirus vectors are able to transduce growth-inhibited cell lines, the cell cycle status of HSCs render them resistant to lentivirus-mediated transduction, and it is hypothesized that entry into cycle, not necessarily division, may be a requirement for efficient lentivirus-mediated transduction. 0006-4971 Journal Article}, Author = {Barrette, S. and Douglas, J. L. and Seidel, N. E. and Bodine, D. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Journal = {Blood}, Keywords = {Human;Tissue Distribution;Lentivirus/*genetics;Animals;Mice, Mutant Strains;Comparative Study;Female;Moloney murine leukemia virus/*genetics;Mice, Inbred C57BL;DNA/metabolism;08 Aberrant cell cycle;Hematopoietic Stem Cells/*metabolism;Hela Cells;Hematopoietic Stem Cell Transplantation;Blotting, Southern;Transduction, Genetic/*standards;Cell Lineage;3T3 Cells;Titrimetry;Hemoglobins/genetics;Retroviridae;Cytokines/pharmacology;Polymerase Chain Reaction;Mice;Genetic Vectors/genetics/standards;Vesicular stomatitis-Indiana virus/genetics;EE, J pdf}, Number = {10}, Organization = {Hematopoiesis Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.}, Pages = {3385-91}, Title = {Lentivirus-based vectors transduce mouse hematopoietic stem cells with similar efficiency to moloney murine leukemia virus-based vectors}, Uuid = {AA1EE43C-211B-43D9-93AE-FED4E4A881E7}, Volume = {96}, Year = {2000}, url = {papers/Barrette_Blood2000.pdf}} @article{Barron:1979, Abstract = {Adult cats survived left lateral funiculotomy 1 to 153 days. The pericruciate cortex was studied electron microscopically in these as well as sham-operated and unoperated animals. Ten days after surgery Betz cells of the right pericruciate cortex displayed disaggregation of cytoplasmic ribosomes; random dispersal and degranulation of the normally compact arrays of cisterns of rough ER; in some cells perinuclear and peripheral disposition of remaining Nissl bodies; retispersion of the Golgi apparatus; and, uncommonly, neurofilamentous hyperplasia. Fourteen days postoperatively cytoplasmic ribosomes were largely regrouped in rosette arrangements and Golgi membranes were evenly distributed in the cytoplasm. Further reversion of the ER toward a normal appearance occurred 28 days postoperatively but substantial perikaryal atrophy had supervened in many neurons by 49-153 days after surgery. Evidence of nerve cell death was not found. Concentric membranous arrays derived from ER and associated with autophagic bodies and mitochondria were identified in dendrites of normals and cats that had been operated upon, perhaps more frequently contralateral to the spinal operation. Electron-dense and electron-lucent degenerative changes in dendrites also occurred, especially early after operation. Degenerating myelin sheaths were detected in the pericruciate cortex of animals that had been operated upon and sometimes were captured in the process of phagocytosis by oligodendrocytes as well as astrocytes and microglia. The long-term persistence of axotomized Betz cells, albeit in an atrophic state, and the reversibility of some of the cytologic responses to axon injury suggest that these neurons may retain a capacity for axon regeneration that could be mobilized, as by pharmacologic means.}, Author = {Barron, K. D. and Dentinger, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Dendrites;Golgi Apparatus;Cats;Myelin Sheath;Not relevant;Endoplasmic Reticulum;11 Glia;Support, U.S. Gov't, P.H.S.;Spinal Cord;Support, Non-U.S. Gov't;Animals;Cerebral Cortex;Cytoplasmic Granules;Axons}, Medline = {81217517}, Month = {3}, Nlm_Id = {2985192R}, Number = {2}, Pages = {128-51}, Pubmed = {261986}, Title = {Cytologic observations on axotomized feline Betz cells. 1. Qualitative electron microscopic findings}, Uuid = {C881D963-239E-465C-AB9C-22E0FC0A187F}, Volume = {38}, Year = {1979}} @article{Barth:1991, Abstract = {This review directly addresses the appropriateness of the dipole model as a physical representation of neocortical sources produced by evoked and spontaneous epileptiform activity in neocortex. Three dimensional electrical measurements of cellular currents in rat sensory neocortex are compared to the extracranial magnetic fields these currents produce. Comparisons are performed for the direct cortical response (DCR) evoked by electrical stimulation of the cortical surface, and for evoked and spontaneous interictal and ictal discharge of the penicillin focus in the same animal preparation. Our data support the hypothesis that evoked and epileptiform magnetic fields result from intradendritic currents oriented perpendicular to the cortical surface. Furthermore, magnetic fields can be detected from epileptic foci smaller than 3 x 3 mm2. This work provides an empirical foundation for physical models with which to interpret noninvasive neuromagnetic recordings of epileptic discharge in human focal seizure disorders. The dipole approximation appears to be appropriate for the interpretation of magnetic field phenomena in neocortex.}, Author = {Barth, D. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0896-0267}, Journal = {Brain Topogr}, Keywords = {Magnetoencephalography;Epilepsies, Partial;Electroencephalography;Research Support, Non-U.S. Gov't;21 Epilepsy;21 Neurophysiology;Rats;Research Support, U.S. Gov't, P.H.S.;Research Support, U.S. Gov't, Non-P.H.S.;Brain Mapping;Animals;Disease Models, Animal;Cerebral Cortex;review;24 Pubmed search results 2008}, Medline = {92172674}, Nlm_Id = {8903034}, Number = {2}, Organization = {Department of Psychology, University of Colorado, Boulder 80309.}, Pages = {85-93}, Pubmed = {1793692}, Title = {Empirical comparison of the MEG and EEG: animal models of the direct cortical response and epileptiform activity in neocortex}, Uuid = {F0241DFD-A8ED-4775-9F66-A05614474BBA}, Volume = {4}, Year = {1991}} @article{Barth:1993, Abstract = {In this review, we present animal studies that evaluate the appropriateness of the dipole model as a physical representation of neocortical sources produced by evoked and spontaneous epileptiform activity in neocortex. Three-dimensional electrical measurements of cellular currents in rat sensory neocortex are compared to associated extracranial magnetic fields. Comparisons are performed for the direct cortical response evoked by electrical stimulation of the cortical surface, and for evoked and spontaneous interictal and ictal discharge of the penicillin focus in the same animal preparation. These data support the hypothesis that evoked and epileptiform magnetic fields result from intradendritic currents oriented perpendicular to the cortical surface. Furthermore, magnetic fields can be detected from epileptic foci smaller than 3 x 3 mm2. Results from animal studies are then used as an empirical foundation for physical models with which to interpret noninvasive neuromagnetic recordings of epileptic discharge in human focal seizure disorders. Examples are presented in which the spatial and temporal distribution of extracranial magnetic fields produced by interictal events in humans may be adequately represented by multiple dipolar sources.}, Author = {Barth, D. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0736-0258}, Journal = {J Clin Neurophysiol}, Keywords = {Epilepsy;Magnetoencephalography;Electroencephalography;21 Epilepsy;21 Neurophysiology;Rats;Animals;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Medline = {93210163}, Month = {1}, Nlm_Id = {8506708}, Number = {1}, Organization = {Department of Psychology, University of Colorado, Boulder 80309.}, Pages = {99-107}, Pubmed = {8458999}, Title = {The neurophysiological basis of epileptiform magnetic fields and localization of neocortical sources}, Uuid = {BD5909DA-35E1-4842-A1F0-1AC0E4219738}, Volume = {10}, Year = {1993}} @article{Barton:2002, Abstract = {Three reports on mammalian brain evolution analyse the same comparative data on brain component volumes but come to partially conflicting conclusions. Clark et al. conclude from their analysis of volumetric brain proportions ("cerebro-types") that cerebellum size is invariant across mammalian taxonomic groups, the neocortex and cerebellum do not co-vary in size (in contradiction to ref. 1), and cerebrotype-based measures identify directional changes in brain architecture. Here I provide evidence that calls each of these conclusions into question. The failure of the cerebrotype measure to identify species differences in brain architecture that are independent of gross brain size undermines the proposal by Clark et al. that it could be useful for detecting evolutionary patterns and phylogenetic relationships. 0028-0836 Comment Journal Article}, Author = {Barton, R. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Nature}, Keywords = {Cerebellum/anatomy &histology;Models, Neurological;Mammals;*Brain/anatomy &histology;Neocortex/anatomy &histology;N;*Evolution;Animals;19 Neocortical evolution}, Number = {6868}, Organization = {Department of Anthropology, University of Durham, UK. r.a.barton\@durham.ac.uk}, Pages = {134-5}, Pubmed = {11805823}, Title = {How did brains evolve?}, Uuid = {9AAAB17C-72BB-4A4A-B8D0-015004CF3D67}, Volume = {415}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11805823}} @article{Basarsky:1998, Abstract = {Spreading depression (SD) was analyzed in hippocampal and neocortical brain slices by imaging intrinsic optical signals in combination with either simultaneous electrophysiological recordings or imaging of intracellular calcium dynamics. The goal was to determine the roles of intracellular calcium (Ca2+int) waves in the generation and propagation of SD. Imaging of intrinsic optical signals in the hippocampus showed that ouabain consistently induced SD, which characteristically started in the CA1 region, propagated at 15-35 micrometer/sec, and traversed across the hippocampal fissure to the dentate gyrus. In the dendritic regions of both CA1 and the dentate gyrus, SD caused a transient increase in light transmittance, characterized by both a rapid onset and a rapid recovery. In contrast, in the cell body regions the transmittance increase was prolonged. Simultaneous imaging of intracellular calcium and intrinsic optical signals revealed that a slow Ca2+int increase preceded any change in transmittance. Additionally, a wave of increased Ca2+int typically propagated many seconds ahead of the change in transmittance. These calcium increases were also observed in individual astrocytes injected with calcium orange, indicating that Ca2+int waves were normally associated with SD. However, when hippocampal slices were incubated in calcium-free/EGTA external solutions, SD was still observed, although Ca2+int waves were completely abolished. Under these conditions SD had a comparable peak increase in transmittance but a slower onset and a faster recovery. These results demonstrate that although there are calcium dynamics associated with SD, these increases are not necessary for the initiation or propagation of spreading depression.}, Author = {Basarsky, T. A. and Duffy, S. N. and Andrew, R. D. and MacVicar, B. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Ouabain;Rats, Sprague-Dawley;Enzyme Inhibitors;21 Neurophysiology;Image Processing, Computer-Assisted;Research Support, Non-U.S. Gov't;Hippocampus;Astrocytes;Rats;Calcium;Neocortex;Organ Culture Techniques;Animals;Brain Chemistry;24 Pubmed search results 2008;Optics;Spreading Cortical Depression}, Medline = {98409769}, Month = {9}, Nlm_Id = {8102140}, Number = {18}, Organization = {Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta Canada T2N 4N1.}, Pages = {7189-99}, Pubmed = {9736642}, Title = {Imaging spreading depression and associated intracellular calcium waves in brain slices}, Uuid = {E6DCEEA0-F3CD-4C5A-AFC3-3A721248374F}, Volume = {18}, Year = {1998}} @article{Bassett:2006, Abstract = {Brain function depends on adaptive self-organization of large-scale neural assemblies, but little is known about quantitative network parameters governing these processes in humans. Here, we describe the topology and synchronizability of frequency-specific brain functional networks using wavelet decomposition of magnetoencephalographic time series, followed by construction and analysis of undirected graphs. Magnetoencephalographic data were acquired from 22 subjects, half of whom performed a finger-tapping task, whereas the other half were studied at rest. We found that brain functional networks were characterized by small-world properties at all six wavelet scales considered, corresponding approximately to classical delta (low and high), , alpha, beta, and gamma frequency bands. Global topological parameters (path length, clustering) were conserved across scales, most consistently in the frequency range 2-37 Hz, implying a scale-invariant or fractal small-world organization. Dynamical analysis showed that networks were located close to the threshold of order/disorder transition in all frequency bands. The highest-frequency gamma network had greater synchronizability, greater clustering of connections, and shorter path length than networks in the scaling regime of (lower) frequencies. Behavioral state did not strongly influence global topology or synchronizability; however, motor task performance was associated with emergence of long-range connections in both beta and gamma networks. Long-range connectivity, e.g., between frontal and parietal cortex, at high frequencies during a motor task may facilitate sensorimotor binding. Human brain functional networks demonstrate a fractal small-world architecture that supports critical dynamics and task-related spatial reconfiguration while preserving global topological parameters.}, Author = {Bassett, Danielle S. and Meyer-Lindenberg, Andreas and Achard, Sophie and Duke, Thomas and Bullmore, Edward}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {7505876}, Number = {51}, Organization = {*Brain Mapping Unit, Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom.}, Pages = {19518-23}, Pii = {0606005103}, Pubmed = {17159150}, Title = {From the Cover: Adaptive reconfiguration of fractal small-world human brain functional networks}, Uuid = {1C74D926-DD10-4B6A-88EB-D9DF52272823}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0606005103}} @article{Bast:2007, Abstract = {OBJECTIVE: The study aimed to evaluate differences between EEG and MEG analysis of early somatosensory evoked activity in patients with focal epilepsies in localizing eloquent areas of the somatosensory cortex. METHODS: Twenty-five patients (12 male, 13 female; age 4-25 years, mean 11.7 years) were included. Syndromes were classified as symptomatic in 17, idiopathic in 2 and cryptogenic in 6 cases. 10 patients presented with malformations of cortical development (MCD). 122 channel MEG and simultaneous 33-channel EEG were recorded during tactile stimulation of the thumb (sampling rate 769 Hz, band-pass 0.3-260 Hz). Forty-four hemispheres were analyzed. Hemispheres were classified as type I: normal (15), II: central structural lesion (16), III: no lesion, but central epileptic discharges (ED, 8), IV: lesion or ED outside the central region (5). Analysis of both sides including one normal and one type II or III hemisphere was possible in 15 patients. Recordings were repeated in 18 hemispheres overall. Averaged data segments were filtered (10-250 Hz) and analyzed off-line with BESA. Latencies and amplitudes of N20 and P30 were analyzed. A regional source was fitted for localizing S1 by MRI co-registration. Orientation of EEG N20 was calculated from a single dipole model. RESULTS: EEG and MEG lead to comparable good results in all normal hemispheres. Only EEG detected N20/P30 in 3 hemispheres of types II/III while MEG showed no signal. N20 dipoles had a more radial orientation in these cases. MEG added information in one hemisphere, when EEG source analysis of a clear N20 was not possible because of a low signal-to-noise ratio. Overall N20 dipoles had a more radial orientation in type II when compared to type I hemispheres (p=0.01). Further N20/P30 parameters (amplitudes, latencies, localization related to central sulcus) showed no significant differences between affected and normal hemispheres. Early somatosensory evoked activity was preserved within the visible lesion in 5 of the 10 patients with MCD. CONCLUSIONS: MEG should be combined with EEG when analyzing tactile evoked activities in hemispheres with a central structural lesion or ED focus. SIGNIFICANCE: At time, MEG analysis is frequently applied without simultaneous EEG. Our results clearly show that EEG may be superior under specific circumstances and combination is necessary when analyzing activity from anatomically altered cortex.}, Author = {Bast, T. and Wright, T. and Boor, R. and Harting, I. and Feneberg, R. and Rupp, A. and Hoechstetter, K. and Rating, D. and Baumg{\"a}rtner, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1388-2457}, Journal = {Clin Neurophysiol}, Keywords = {Touch;Magnetoencephalography;Magnetic Resonance Imaging;Epilepsies, Partial;Child, Preschool;Humans;Female;Child;Physical Stimulation;research support, non-u.s. gov't;Male;evaluation studies;Evoked Potentials, Somatosensory;21 Neurophysiology;Cerebral Cortex;Adult;24 Pubmed search results 2008;Electroencephalography;Adolescent}, Month = {8}, Nlm_Id = {100883319}, Number = {8}, Organization = {Department of Pediatric Neurology, University Children's Hospital, INF 150, 69120 Heidelberg, Germany. Thomas\_Bast\@med.uni-heidelberg.de}, Pages = {1721-35}, Pii = {S1388-2457(07)00196-4}, Pubmed = {17572142}, Title = {Combined EEG and MEG analysis of early somatosensory evoked activity in children and adolescents with focal epilepsies}, Uuid = {5E2042F4-E453-48D0-8A3E-3ACA4A2C4A4F}, Volume = {118}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.clinph.2007.03.037}} @article{Basu:2002, Abstract = {Interleukin-1 (IL-1) is induced immediately after insults to the brain, and elevated levels of IL-1 have been strongly implicated in the neurodegeneration that accompanies stroke, Alzheimer's disease, and multiple sclerosis. In animal models, antagonizing IL-1 has been shown to reduce cell death; however, the basis for this protection has not been elucidated. Here we analyzed the response to penetrating brain injury in mice lacking the type 1 IL-1 receptor (IL-1R1) to determine which cellular and molecular mediators of tissue damage require IL-1 signaling. At the cellular level, fewer amoeboid microglia/macrophages appeared adjacent to the injured brain tissue in IL-1R1 null mice, and those microglia present at early postinjury intervals retained their resting morphology. Astrogliosis also was mildly abrogated. At the molecular level, cyclooxygenase-2 (Cox-2) and IL-6 expression were depressed and delayed. Interestingly, basal levels of Cox-2, IL-1, and IL-6 were significantly lower in the IL-1R1 null mice. In addition, stimulation of vascular cell adhesion molecule-1 mRNA was depressed in the IL-1R1 null mice, and correspondingly, there was reduced diapedesis of peripheral macrophages in the IL-1R1 null brain after injury. This observation correlated with a reduced number of Cox-2+ amoeboid phagocytes adjacent to the injury. In contrast, several molecular aspects of the injury response were normal, including expression of tumor necrosis factor-alpha and the production of nerve growth factor. Because antagonizing IL-1 protects neural cells in experimental models of stroke and multiple sclerosis, our data suggest that cell preservation is achieved by abrogating microglial/macrophage activation and the subsequent self-propagating cycle of inflammation. 22117912 1529-2401 Journal Article}, Author = {Basu, A. and Krady, J. K. and O'Malley, M. and Styren, S. D. and DeKosky, S. T. and Levison, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Cytokines/genetics/metabolism;Prostaglandin-Endoperoxide Synthase/genetics/metabolism;Signal Transduction;Macrophages/metabolism/pathology;Prostaglandins/metabolism;Cyclophilins/genetics/metabolism;Isoenzymes/genetics/metabolism;Animal;Cell Count;Interleukin-1/metabolism;Inflammation Mediators/*metabolism;11 Glia;G abstr;Disease Models, Animal;Male;Macrophage Activation;Neurons/metabolism/pathology;Support, Non-U.S. Gov't;Microglia/*metabolism/pathology;Mice, Inbred C57BL;Head Injuries, Penetrating/*physiopathology;Receptors, Interleukin-1/deficiency/genetics/*metabolism;Gliosis/pathology/prevention &control;Interleukin-6/genetics/metabolism;Mice, Knockout;Vascular Cell Adhesion Molecule-1/genetics/metabolism;Mice;RNA, Messenger/metabolism}, Number = {14}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.}, Pages = {6071-82}, Pubmed = {12122068}, Title = {The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury}, Uuid = {1E802FDB-B489-432F-A9F0-7CCCF5443C0D}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12122068}} @article{Baszler:1991, Abstract = {To determine the biologic basis of ts1 MoMuLV neurovirulence in vivo, newborn CFW/D mice were inoculated with neurovirulent ts1 MoMuLV and nonneurovirulent wt MoMuLV and the temporal response to virus infection in the central nervous system (CNS), spleen, and thymus was studied comparatively. Experimental procedures included single and double labeling in situ immunohistochemistry with selective morphometric analyses, and steady state immunoblotting of viral proteins. Cellular targets for virus infection were identical for both ts1 and wt MoMuLV and consisted sequentially of 1) splenic megakaryocytes, 2) splenic and thymic lymphocytes, 3) CNS capillary endothelial cells, and 4) CNS pericytes and microglia. Resident microglial cells served as the major reservor and amplifier of virus infection in the CNS of ts1 MoMuLV-infected mice; a similar but much less significant role was played by microglia in wt MoMuLV-infected mice. The genesis and progression of severe spongiform lesions in ts1 MoMuLV-infected mice were both temporally and spatially correlated with amplified virus infection of microglia, and hyperplasia and hypertrophy of both virus-infected and nonvirus-infected microglial cells. Direct virus infection of neurons was never observed. The development of clinical neurologic disease and spongiform lesions in ts1 MoMuLV-infected mice correlated with the accumulation of both viral gag and env gene products in the CNS; there was no selective accumulation of env precursor polyprotein Pr80env. When compared to wt MoMuLV-infected mice, the neurovirulence of ts1 MoMuLV-infected mice occurred by an enhanced ability to replicate in the CNS and to infect and activate more microglia, rather than by a fundamental change in cellular tropism or topography of virus infection.}, Author = {Baszler, T. V. and Zachary, J. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Antibodies, Viral;Mice, Inbred Strains;Virulence;Central Nervous System;Immunoblotting;Moloney murine leukemia virus;Virus Replication;Immunohistochemistry;Not relevant;Thymus Gland;Viral Proteins;11 Glia;Mice;Support, Non-U.S. Gov't;Spleen;Animals;Central Nervous System Diseases}, Medline = {91157972}, Month = {3}, Nlm_Id = {0370502}, Number = {3}, Organization = {Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana.}, Pages = {655-71}, Pubmed = {2000941}, Title = {Murine retroviral neurovirulence correlates with an enhanced ability ofvirus to infect selectively, replicate in, and activate resident microglial cells}, Uuid = {94AC3012-95EB-48DC-9B7D-256DF7B18769}, Volume = {138}, Year = {1991}} @article{Baszler:1990, Abstract = {Ts1 Moloney murine leukemia virus (MoMuLV) is a neurovirulent retrovirus that causes a progressive, noninflammatory, spongiform, neurodegenerative disease in mice. The temporal localization of cellular targets for virus replication and the genesis of ultrastructural spongiform changes in the central nervous system (CNS) of CFW/D mice inoculated at birth with neurovirulent ts1 MoMuLV and nonneurovirulent wild type (wt) MoMuLV were studied comparatively by transmission electron microscopy. Cellular targets for both ts1 and wt MoMuLV infection were sequentially (a) splenic megakaryocytes, (b) CNS intravascular platelets and capillary endothelia, and (c) resident CNS pericytes and microglia. When compared with wt MoMuLV-infected mice, ts1 MoMuLV-infected mice had amplified localization of virus to microglia with disease progression that paralleled the development of spongiform changes both temporally and spatially. Virus infection of neurons was never observed. Spongiform lesions originated from the dilated cytocavitary system of proximal neuronal processes (predominantly dendrites) and from vacuolated myelin sheaths of distal axons. As the disease progressed, the severity of the spongiform lesions in ts1 MoMuLV-infected mice increased rapidly and was associated with increased number of virions and virus-infected cells. Lesions in wt MoMuLV-infected mice were not severe and regressed terminally with apparent clearance of virus from the CNS. These studies indicated that murine retroviral-induced spongiform lesions originated from both neuronal and oligodendroglial degeneration; splenic megakaryocytes, platelets, and cell-free viremia contributed to systemic dissemination of virus to the CNS; microglia were the major cell target and reservoir for virus infection in the CNS; and the neurovirulence of ts1 MoMuLV occurred by enhanced replication rather than by a fundamental change in cellular tropism. The identification of microglia as the major CNS cell target for virus infection and the absence of productive virus infection of neurons suggested an indirect mechanism for murine retroviral-induced neuronal dysfunction.}, Author = {Baszler, T. V. and Zachary, J. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0023-6837}, Journal = {Lab Invest}, Keywords = {Mice, Inbred Strains;Mutation;Animals;Neuroglia;Nerve Degeneration;Virus Replication;Not relevant;11 Glia;Support, Non-U.S. Gov't;Spleen;Leukemia Virus, Murine;Central Nervous System Diseases;Mice}, Medline = {91040713}, Month = {11}, Nlm_Id = {0376617}, Number = {5}, Organization = {Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana.}, Pages = {612-23}, Pubmed = {2172651}, Title = {Murine retroviral-induced spongiform neuronal degeneration parallels resident microglial cell infection: ultrastructural findings}, Uuid = {B06DE214-F8F5-48BB-9BFB-5E145F52BDA3}, Volume = {63}, Year = {1990}} @article{Bathellier:2006, Abstract = {Optical imaging techniques offer powerful solutions to capture brain networks processing in animals, especially when activity is distributed in functionally distinct spatial domains. Despite the progress in imaging techniques, the standard analysis procedures and statistical assessments for this type of data are still limited. In this paper, we perform two in vivo non-invasive optical recording techniques in the mouse olfactory bulb, using a genetically expressed activity reporter fluorescent protein (synaptopHfluorin) and intrinsic signals of the brain. For both imaging techniques, we show that the odour-triggered signals can be accurately parameterized using linear models. Fitting the models allows us to extract odour specific signals with a reduced level of noise compared to standard methods. In addition, the models serve to evaluate statistical significance, using a wavelet-based framework that exploits spatial correlation at different scales. We propose an extension of this framework to extract activation patterns at specific wavelet scales. This method is especially interesting to detect the odour inputs that segregate on the olfactory bulb in small spherical structures called glomeruli. Interestingly, with proper selection of wavelet scales, we can isolate significantly activated glomeruli and thus determine the odour map in an automated manner. Comparison against manual detection of glomeruli shows the high accuracy of the proposed method. Therefore, beyond the advantageous alternative to the existing treatments of optical imaging signals in general, our framework propose an interesting procedure to dissect brain activation patterns on multiple scales with statistical control.}, Author = {Bathellier, and Van De Ville, and Blu, and Unser, and Carleton,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1053-8119}, Journal = {Neuroimage}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9215515}, Organization = {Flavour Perception Group, Brain Mind Institute, Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, (EPFL), CH-1015, Switzerland; Laboratory of Computational Neuroscience, Brain Mind Institute, Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, (EPFL), CH-1015, Switzerland.}, Pii = {S1053-8119(06)01074-3}, Pubmed = {17185002}, Title = {Wavelet-based multi-resolution statistics for optical imaging signals: Application to automated detection of odour activated glomeruli in the mouse olfactory bulb}, Uuid = {4D975E73-5A51-4F23-A2AD-7BDD026C3BD0}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2006.10.038}} @article{Batista:2006, Abstract = {Neural stem and progenitor cells are located in the subependyma of the adult forebrain. An increase in adult subependymal cell proliferation is reported after various kinds of brain injury. We demonstrate an expansion of neural precursor cells in the postnatal subependyma in a murine genetic disease model of Huntington's disease (HD), the R6/2 mouse. We used the in vitro neurosphere assay as an index of the number of neural stem cells in vivo and to assess proliferation kinetics in vitro and in vivo bromodeoxyuridine labeling to assess the progenitor cell population and their fates. Disease progression in this model leads to an increase in the numbers of neural stem cells in the adult striatal subependyma. This increase is produced cell non-autonomously by events in the R6/2 brains as the mice become increasingly symptomatic. Once the neural stem cell increase is induced in vivo, it is maintained during in vitro passaging of neural stem cells, but the neural stem cell increase is not reproduced during in vitro passaging of neural stem cells from presymptomatic R6/2 mice. In addition, we show that some of the R6/2 neural progenitor cells show a change from their normal migration destiny toward the olfactory bulb. Instead, some of these cells migrate into the striatum, one of the main affected areas in HD. Our findings demonstrate that HD damage recruits precursor cells in two ways: expansion of neural stem cells and altered migration of progenitor cells.}, Author = {Batista, Claudia M. C. and Kippin, Tod E. and Willaime-Morawek, Sandrine and Shimabukuro, Mar{\'\i}lia Kimie and Akamatsu, Wado and van der Kooy, Derek}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Mice, Neurologic Mutants;Neurons;24 Pubmed search results 2008;Huntington Disease;Cell Proliferation;research support, non-u.s. gov't ;Stem Cells;Corpus Striatum;Animals;comparative study ;Cell Movement;Humans;Mice}, Month = {10}, Nlm_Id = {8102140}, Number = {41}, Organization = {Neurobiology Research Group, Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario, Canada M5S 3E1.}, Pages = {10452-60}, Pii = {26/41/10452}, Pubmed = {17035529}, Title = {A progressive and cell non-autonomous increase in striatal neural stem cells in the Huntington's disease R6/2 mouse}, Uuid = {39A451D7-1C7B-4290-B384-0D757833C657}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2850-06.2006}} @article{Battaglia:1997, Abstract = {PURPOSE: We studied 17 patients with periventricular nodular heterotopia (PNH) to further investigate the electroclinical pictures and semiology of the associated seizures. METHODS: PNH was diagnosed by means of magnetic resonance imaging (MRI). The patients' clinical and familial histories were carefully analyzed, and their electroclinical features and course of epilepsy followed for periods ranging from 10 months to 22 years. The electroclinical data were compared with those of previously reported PNH cases. RESULTS: The patients were subdivided into those with bilateral (7) and unilateral (10) PNH. The former were mainly characterized by structural abnormalities in the posterior cerebral fossa and multiple seizure types; the latter were characterized by the paratrigonal location of the malformation and, frequently, by elementary seizures with a visual or auditory onset. Focal seizures were drug resistant in most cases. The interictal EEG abnormalities were always focal and consistent with the location of the PNH. A previously unreported photic driving of posterior background activity was observed in all patients and was always consistent with the PNH location. CONCLUSIONS: Our present findings and previously reported data show that bilateral and unilateral PNH cases are different in their morphological and electroclinical features and may be determined by different etiologies. The female predominance, frequent familial occurrence, and positive family history for epilepsy suggest that genetic factors may be involved in the genesis of bilateral and symmetrical PNH, whereas the presence of prenatal risk factors and its location in the watershed paratrigonal area suggest that vascular mechanisms may determine unilateral PNH.}, Author = {Battaglia, G. and Granata, T. and Farina, L. and D'Incerti, L. and Franceschetti, S. and Avanzini, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:40 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {10 Development;Magnetic Resonance Imaging;Humans;Middle Aged;Age of Onset;Functional Laterality;Brain;Female;Epilepsy;Sex Factors;research support, non-u.s. gov't;Male;Neurologic Examination;10 genetics malformation;Cerebral Cortex;Neurons;Adult;24 Pubmed search results 2008;Choristoma;Electroencephalography;Adolescent}, Month = {11}, Nlm_Id = {2983306R}, Number = {11}, Organization = {Department of Neurophysiology, C. Besta Neurological Institute, Milan, Italy.}, Pages = {1173-82}, Pubmed = {9579917}, Title = {Periventricular nodular heterotopia: epileptogenic findings}, Uuid = {15539F3B-CFCA-4FA7-96DD-D899120B7C3E}, Volume = {38}, Year = {1997}, url = {papers/Battaglia_Epilepsia1997.pdf}} @article{Battaglia:1996, Abstract = {Despite the increasing number of patients affected by neuronal migration disorders (NMDs) recently diagnosed in vivo by means of magnetic resonance imaging (MRI), few detailed data on the correlation between the neuroradiological and the anatomical features in the single NMD case are available. The present paper reports a combined cytoarchitectural and immunocytochemical analysis, by means of antisera recognizing specific neuronal and glial markers, of three MRI diagnosed NMD patients surgically treated for the relief of intractable seizures. The first case was a giant subcortical nodular heterotopia of morphologically normal neurons lacking any type of cortical lamination. The second case was a layered polymicrogyria with an abnormal amount of ectopic neurons in the underlying white matter. The third case was a focal cortical dysplasia characterized by a dramatic disruption of the normal cortical layering associated with marked cytological abnormalities. The present data demonstrate that the macroscopical and microscopical brain abnormalities can be markedly different in different NMD subtypes, and suggest that different anatomical substrates can underlie the intrinsic hyperexcitability of these brain malformations. The relevance of further prospective clinico-morphological studies for a better understanding of the mechanisms determining the development of these brain malformations is underlined.}, Author = {Battaglia, G. and Arcelli, P. and Granata, T. and Selvaggio, M. and Andermann, F. and Dubeau, F. and Olivier, A. and Tampieri, D. and Villemure, J. G. and Avoli, M. and Avanzini, G. and Spreafico, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Epilepsy;Brain;24 Pubmed search results 2008;Neuroglia;Research Support, Non-U.S. Gov't;21 Neurophysiology;Magnetic Resonance Imaging;Female;Immunohistochemistry;21 Epilepsy;Choristoma;Humans;Male;Immune Sera;Neurons;case reports}, Medline = {97138662}, Month = {12}, Nlm_Id = {8703089}, Number = {1}, Organization = {Neurological Institute C. Besta, Milan, Italy.}, Pages = {49-58}, Pii = {S0920121196000393}, Pubmed = {8985686}, Title = {Neuronal migration disorders and epilepsy: a morphological analysis of three surgically treated patients}, Uuid = {1FAFEC44-D5B2-40E6-9DDD-CD156D2C0A66}, Volume = {26}, Year = {1996}} @article{Battista:2006, Abstract = {Adult neural stem cells (NSC) proliferate and differentiate depending on the composition of the cellular and molecular niche in which they are immersed. Until recently, microglial cells have been ignored as part of the neurogenic niche. We studied the dynamics of NSC proliferation and differentiation in the dentate gyrus of the hippocampus (DG) and characterized the changes of the neurogenic niche in adrenalectomized animals (ADX). At the cellular level, we found increased NSC proliferation and neurogenesis in the ADX animals. In addition, a morphologically distinct subpopulation of NSC (Nestin+/GFAP-) with increased proliferating profile was detected. Interestingly, the number of microglial cells at stages 2 and 3 of activation correlated with increased neurogenesis (r(2) = 0.999) and the number of Nestin-positive cells (r(2) = 0.96). At the molecular level, transforming growth factor beta (TGF-beta) mRNA levels were increased 10-fold in ADX animals. Interestingly, TGF-beta levels correlated with the amount of neurogenesis detected (r(2) = 0.99) and the number of stage 2 and 3 microglial cells (r(2) = 0.94). Furthermore, blockade of TGF-beta biological activity by administration of an anti-TGF-beta type II receptor antibody diminished the percentage of 5-bromo-2'-deoxyuridine (BrdU)/PSA-NCAM-positive cells in vivo. Moreover, TGF-beta was able to promote neurogenesis in NSC primary cultures. This work supports the idea that activated microglial cells are not pro- or anti-neurogenic per se, but the balance between pro- and anti-inflammatory secreted molecules influences the final effect of this activation. Importantly, we identified an anti-inflammatory cytokine, TGF-beta, with neurogenic potential in the adult brain.}, Author = {Battista, Daniela and Ferrari, Carina C. and Gage, Fred H. and Pitossi, Fernando J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {8918110}, Number = {1}, Organization = {Laboratory of Neuromodulation, Leloir Institute, CONICET-UBA, University of Buenos Aires, 435 Av Patricias Argentinas, Buenos Aires 1405, Argentina.}, Pages = {83-93}, Pii = {EJN4539}, Pubmed = {16420418}, Title = {Neurogenic niche modulation by activated microglia: transforming growth factor beta increases neurogenesis in the adult dentate gyrus}, Uuid = {3721E8EF-BFD2-49D2-90B6-BA3AE6E87EFB}, Volume = {23}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2005.04539.x}} @article{Baude:2007, Abstract = {Parvalbumin (PV)-expressing interneurons synchronize cortical neurons through gamma-aminobutyric acidergic (GABAergic) synapses. Three types of PV-containing interneurons populate stratum pyramidale of the hippocampal CA1 area: basket cells targeting somata and proximal dendrites, axoaxonic cells innervating axon initial segments, and bistratified cells targeting the dendrites of pyramidal cells. We tested whether this axonal specialization is accompanied by a differential expression of molecules involved in neuronal signaling. Immunofluorescence evaluation of interneurons labeled by neurobiotin in vivo shows that axoaxonic cells express significantly less GABA(A) receptor alpha1 subunit in the plasma membrane than basket and bistratified cells. Electron microscopic immunogold labeling reveals that this subunit contributes heavily to extrasynaptic receptors providing a substrate for tonic inhibition. Results from additional immunofluorescence experiments were consistent with the finding that only bistratified cells express the neuropeptide somatostatin. From the molecular profiles, we estimate that basket, bistratified, and axoaxonic cells represent about 60\%, 25\%, and 15\%, respectively, of PV-containing cells in CA1 stratum pyramidale. In addition, all 3 interneuron classes form connexin36-immunopositive dendrodendritic gap junctions. The differential expression of signaling molecules and the relative frequency of cells reflect the specialized temporal contribution of the 3 types of PV-positive interneurons to GABA release in the network.}, Author = {Baude, Agn\`{e}s and Bleasdale, Catherine and Dalezios, Yannis and Somogyi, Peter and Klausberger, Thomas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Animals;Image Processing, Computer-Assisted;Rats;Microscopy, Confocal;Fluorescent Antibody Technique;Axons;Rats, Sprague-Dawley;Hippocampus;Connexins;research support, non-u.s. gov't;Pyramidal Tracts;Male;Receptors, GABA-A;Somatostatin;Peroxidase;Interneurons;24 Pubmed search results 2008;Immunohistochemistry}, Month = {9}, Nlm_Id = {9110718}, Number = {9}, Organization = {MRC Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford University, Oxford OX1 3TH, UK.}, Pages = {2094-107}, Pii = {bhl117}, Pubmed = {17122364}, Title = {Immunoreactivity for the GABAA receptor alpha1 subunit, somatostatin and Connexin36 distinguishes axoaxonic, basket, and bistratified interneurons of the rat hippocampus}, Uuid = {FCEB5579-C5CB-41CB-BD65-87C732FE48AC}, Volume = {17}, Year = {2007}, url = {papers/Baude_CerebCortex2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhl117}} @article{Bauer:1995, Abstract = {Clinical signs of experimental autoimmune encephalomyelitis (EAE) in rats can be suppressed by treatment with liposomes containing dichloromethylene diphosphonate (Cl2MDP liposomes). Here we investigated whether besides the blood-borne macrophages also ED2+ perivascular cells and microglia are affected by this treatment. For this purpose we examined the central nervous system of bone marrow chimeras in which EAE was induced with encephalitogenic T cells. Quantification of cell numbers of various cell types in inflammatory lesions in the spinal cord showed that after treatment with Cl2MDP liposomes more than 95\%of the bone marrow derived (I1-69+) macrophages were eliminated. In addition the number of ED2+ perivascular cells were seen to be decreased by 68\%as compared to ED2+ cells in control liposome treated animals. However the number of these perivascular cells in Cl2MDP liposome treated animals did not differ from the number of perivascular cells in naive animals, indicating that only newly recruited, inflammation associated, ED2+ macrophages were eliminated. Moreover, detection of degenerating nuclei by in situ nick translation (ISNT) in combination with staining for ED1 or ED2 showed that in the perivascular space no degenerating cells were present. Cl2MDP liposome treatment furthermore decreased the numbers of T cells infiltrating the parenchyma by more than 50\%. Instead T cells were found in large numbers in the perivascular space. Microglia did not seem to be eliminated by Cl2MDP liposome treatment as shown by the absence of ED1+/ISNT+ cells in the CNS parenchyma. However the number of ED1+ (I1-69-) microglial cells decreased by more than 80\%, indicating that the activation of this cell type was impaired. It is concluded that bone marrow derived macrophages play an important role in the pathogenesis of EAE via interactions with lymphocytes and the activation of resident microglia.}, Author = {Bauer, J. and Huitinga, I. and Zhao, W. and Lassmann, H. and Hickey, W. F. and Dijkstra, C. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Research Support, Non-U.S. Gov't;Central Nervous System;Rats, Inbred Lew;Rats;Research Support, U.S. Gov't, P.H.S.;Encephalomyelitis, Autoimmune, Experimental;T-Lymphocytes;11 Glia;Microglia;Macrophages;Rats, Inbred BN;Spinal Cord;Animals;Spleen}, Medline = {96275083}, Month = {12}, Nlm_Id = {8806785}, Number = {4}, Organization = {Department of Cell Biology and Immunology, Vrije Universiteit, Amsterdam, Netherlands.}, Pages = {437-46}, Pubmed = {8926037}, Title = {The role of macrophages, perivascular cells, and microglial cells in the pathogenesis of experimental autoimmune encephalomyelitis}, Uuid = {369161B7-8ECC-486B-BA35-CD62E11BFCC2}, Volume = {15}, Year = {1995}} @article{Bauer:2005, Abstract = {Adult neurogenesis is studied in vivo using thymidine analogues such as bromodeoxyuridine (BrdU) to label DNA synthesis during the S phase of the cell cycle. However, BrdU may also label DNA synthesis events not directly related to cell proliferation, such as DNA repair and/or abortive reentry into the cell cycle, which can occur as part of an apoptotic process in postmitotic neurons. In this study, we used three well-characterized models of injury-induced neuronal apoptosis and the combined visualization of cell birth (BrdU labeling) and death (Tdt-mediated dUTP-biotin nick end labeling) to investigate the specificity of BrdU incorporation in the adult mouse brain in vivo. We present evidence that BrdU is not significantly incorporated during DNA repair and that labeling is not detected in vulnerable or dying postmitotic neurons, even when a high dose of BrdU is directly infused into the brain. These findings have important implications for a controversy surrounding adult neurogenesis: the connection between cell cycle reactivation and apoptosis of terminally differentiated neurons.}, Author = {Bauer, Sylvian and Patterson, Paul H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {01 Adult neurogenesis general;08 Aberrant cell cycle;06 Adult neurogenesis injury induced}, Month = {11}, Nlm_Id = {0375356}, Number = {4}, Organization = {Biology Division, California Institute of Technology, Pasadena, CA 91125.}, Pages = {641-50}, Pii = {jcb.200505072}, Pubmed = {16291699}, Title = {The cell cycle-apoptosis connection revisited in the adult brain}, Uuid = {B65BD976-AD3C-11DA-B832-000D9346EC2A}, Volume = {171}, Year = {2005}, url = {papers/Bauer_JCellBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200505072}} @article{Bauer:2006, Abstract = {Although neural stem cells (NSCs) persist in various areas of the adult brain, their contribution to brain repair after injury is very limited. Treatment with exogenous growth factors can mitigate this limitation, suggesting that the brain environment is normally deficient in permissive cues and that it may be possible to stimulate the latent regenerative potential of endogenous progenitors with appropriate signals. We analyzed the effects of overexpressing the cytokine leukemia inhibitory factor (LIF) on adult neurogenesis in the normal brain. We found that LIF reduces neurogenesis in the olfactory bulb and subventricular zone by acting directly on NSCs. LIF appears to promote NSC self-renewal, preventing the emergence of more differentiated cell types. This ultimately leads to an expansion of the NSC pool. Our results have implications for the development of therapeutic strategies for brain repair and suggest that LIF may be useful, in combination with other factors, in promoting regeneration in the adult brain.}, Author = {Bauer, Sylvian and Patterson, Paul H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Spheroids, Cellular;Cell Differentiation;Animals;Cells, Cultured;Transfection;Neuronal Plasticity;Telencephalon;Mice, Inbred C57BL;Nerve Growth Factors;research support, non-u.s. gov't;Antimitotic Agents;Cell Proliferation;Nerve Regeneration;Injections, Intraventricular;Male;Genetic Vectors;Leukemia Inhibitory Factor;Neuroglia;Neurons;Adenoviridae;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Bromodeoxyuridine;Stem Cells}, Month = {11}, Nlm_Id = {8102140}, Number = {46}, Organization = {Biology Division, California Institute of Technology, Pasadena, California 91125, USA.}, Pages = {12089-99}, Pii = {26/46/12089}, Pubmed = {17108182}, Title = {Leukemia inhibitory factor promotes neural stem cell self-renewal in the adult brain}, Uuid = {3A19E9E8-DCF7-48A2-A087-61BD11901E4B}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3047-06.2006}} @article{Baus:2003, Abstract = {Although the Cdk inhibitor p21(Waf1/Cip1), one of the transcriptional targets of p53, has been implicated in the maintenance of G(2) arrest after DNA damage, its function at this stage of the cell cycle is not really understood. Here, we show that the exposure of normal human fibroblasts (NHFs) to genotoxic agents provokes permanent cell cycle exit in G(2) phase, whereas mouse embryo fibroblasts and transformed human cells progress through mitosis and arrest in G(1) without intervening cytokinesis. p21(Waf1/Cip1) exerts a key role in driving this G(2) exit both by inhibiting cyclin B1-Cdk1 and cyclin A-Cdk1/2 complexes, which control G(2)/M progression, and by blocking the phosphorylation of pRb family proteins. NHFs with compromised pRb proteins could still efficiently arrest in G(2) but were unable to exit the cell cycle, resulting in cell death. Our experiments show that, when under continuous genotoxic stress, normal cells can reverse their commitment to mitotic progression due to passage through the restriction point and that mechanisms involving p21(Waf1/Cip1) and pocket proteins can induce exit in G(2) and G(1). 0261-4189 Journal Article}, Author = {Baus, F. and Gire, V. and Fisher, D. and Piette, J. and Dulic, V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:41 -0400}, Journal = {Embo J}, Keywords = {EE pdf;*DNA Damage;Human;08 Aberrant cell cycle;Fibroblasts/cytology/metabolism;Piperazines/pharmacology;Bleomycin/pharmacology;Cyclin-Dependent Kinases/metabolism;Cyclins/metabolism;Mitosis;Support, Non-U.S. Gov't;Cells, Cultured;*G2 Phase}, Number = {15}, Organization = {CRBM-CNRS FRE 2593, 1919, Route de Mende, 34293 Montpellier, IGMM-CNRS UMR 5535, Montpellier and IGH-CNRS UPR 1142, Montpellier, France.}, Pages = {3992-4002}, Title = {Permanent cell cycle exit in G2 phase after DNA damage in normal human fibroblasts}, Uuid = {EBE2D712-3E34-47DE-BC25-2D0007DA36D7}, Volume = {22}, Year = {2003}, url = {papers/Baus_EmboJ2003.pdf}} @article{Bavister:1988, Abstract = {Construction details are described for a minichamber device that maintains a localized atmosphere of carbon dioxide in air over the stage of an inverted microscope. This device is easily constructed from Plexiglas and its specifications can be adjusted to fit virtually any inverted microscope. A flow of warm, humidified carbon dioxide in air gas mixture can be directed over a petri dish or unsealed culture flask to maintain the pH of bicarbonate-CO2 buffered media. By this means, prolonged culture of cells directly on the microscope stage is made possible without occurrence of detrimental pH changes. If the microscope is fitted with an environmental control chamber to maintain temperature, cells can be maintained on the microscope stage for days, permitting frequent observation of cell growth and activity. Alternatively, continuous cine or video recordings can be made. For example, using this device, hamster and rhesus monkey embryos have been cultured for 2 to 5 d on an inverted microscope while continuous time- lapse recordings were made of cell division and differentiation and activity of cellular organelles.}, Author = {Bavister, B. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {In Vitro Cell Dev Biol}, Keywords = {23 Technique;Atmosphere;Macaca mulatta/embryology;Time Factors;Cells, Cultured/*physiology;T abstr;Animal;Hamsters/embryology;Support, U.S. Gov't, P.H.S.;*Carbon Dioxide;Support, Non-U.S. Gov't;Ectogenesis;Microscopy/*instrumentation}, Number = {8}, Organization = {Wisconsin Regional Primate Research Center, University of Wisconsin, Madison 53706.}, Pages = {759-63.}, Title = {A minichamber device for maintaining a constant carbon dioxide in air atmosphere during prolonged culture of cells on the stage of an inverted microscope}, Uuid = {616D7C57-00A7-4115-8415-5C3E81654C20}, Volume = {24}, Year = {1988}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3137208}} @article{Bayer:1982, Abstract = {The total number of granule cells in the dentate gyrus was estimated in 17 male rats, four each aged 30, 120, and 200 days, and five aged 365 days. There is a substantial 35-43\%linear increase between 1 month and 1 year. Two parameters of the granular layer are involved in the numerical change. First, total granular layer volume grows linearly with age. Second, average volume of a single granule cell nucleus in the ventral dentate gyrus decreases with age. Older rats tend to have a larger granular layer filled with more and smaller cells. In another group of 21 male rats, 3H-thymidine injections were given on four consecutive days during juvenile (30-33, n = 6) and adult life (60-63, n = 5; 120-123, n = 6; 180-183, n = 4). All animals survived to 200 days of age. The proportion of labeled mature granule cells and labeled presumptive granule cell precursors were determined in anatomically- matched slices. With older ages at injection, there is a decline in labeled mature granule cells and a concurrent increase in labeled precursors. These data are compatible with the constant level of granule cell increase determined volumetrically. Most of the late granule cells originate nearly simultaneously along the base of the main bulk of the granular layer; very few are found in the dorsal tip (septal extreme) and ventral tip (temporal extreme). This study is the first demonstration of a net numerical gain in a neuronal population during adulthood in the mammalian brain. Since the granule adulthood in the mammalian brain. Since the granule cells play a pivotal role in hippocampal function, these data suggest that their influence grows with age. Using Smart Source Parsing}, Author = {Bayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Exp Brain Res}, Keywords = {02 Adult neurogenesis migration;Cell Differentiation;10 Development;B;Rats;10 Hippocampus;Autoradiography;Thymidine/metabolism;Cell Division;Cell Count;Hippocampus/*cytology/metabolism;Support, U.S. Gov't, Non-P.H.S.;Animal;Male;Rats, Inbred Strains}, Number = {3}, Pages = {315-23}, Title = {Changes in the total number of dentate granule cells in juvenile and adult rats: a correlated volumetric and 3H-thymidine autoradiographic study}, Uuid = {FE6D5715-C36A-4362-A5D3-85538781C60F}, Volume = {46}, Year = {1982}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7095040}} @article{Bayer:1983, Abstract = {Neurogenesis in the rat olfactory bulb was examined with 3H-thymidine- radiography. For the animals in the prenatal groups, the initial 3H- thymidine exposures were separated by 24 h; they were the offspring of pregnant females given two injections on consecutive embryonic (E) days (E12-E13, E13-E14, . . . E21-E22). For the animals in the postnatal (P) groups, the initial 3H-thymidine injections were separated by 48 h, each group receiving either four (PO-P3, P2-P4, . . . P6-P9) or two (P8- P9, P10-P11, . . . P20-P21) consecutive daily injections. On P60, the percentage of labeled cells and the proportion of cells added during either 24 h or 48 h periods were quantified at several anatomical levels for each neuronal population in the main olfactory bulb (mitral cells, tufted cells, granule cells, interneurons in the external plexiform layer, periglomerular granule cells) and accessory olfactory bulb (output neurons, granule cells, periglomerular granule cells). The total time span of neurogenesis extends from E12 to beyond P20. Output neurons are prenatally generated over 5-9 day periods (with most neurogenesis occurring over 2-4 days) in a strict sequential order beginning with the accessory bulb output neurons (E13-E14) and ending with the interstitial tufted cells lying between the glomeruli in the main bulb (E20-E22). These data are correlated with the main and accessory bulb projection fields in the amygdala and with the chronology of amygdala neurogenesis. With the exception of the granule cells in the accessory bulb (88\%generated between E15-E22), the rest of the interneuronal populations are generated postnatally and nearly simultaneously. While most neurons (75-80\%) originate during the first three weeks of life, all interneuronal populations, including accessory bulb granule cells, show some neurogenesis beyond P20. Injections of 3H- thymidine in juvenile and adult rats indicates neurogenesis up to P60 in the accessory bulb and up to P180 in the main bulb, especially in the main bulb granule cell population. There is circumstantial evidence for turnover of main bulb granule cells during adult life. Using Smart Source Parsing}, Author = {Bayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Exp Brain Res}, Keywords = {A;01 Adult neurogenesis general;Cell Differentiation;10 Development;Interneurons/cytology;Rats;10 Hippocampus;Cell Division;Animal;Support, U.S. Gov't, Non-P.H.S.;Olfactory Bulb/embryology/*growth &development/metabolism;Thymidine/*metabolism;Rats, Inbred Strains}, Number = {2-3}, Pages = {329-40}, Title = {3H-thymidine-radiographic studies of neurogenesis in the rat olfactory bulb}, Uuid = {BFFA96EF-4732-48E0-82CB-9D854FE6888E}, Volume = {50}, Year = {1983}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=6641865}} @article{Bayer:1980, Author = {Bayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Thymidine;Thalamic Nuclei;Cell Differentiation;Septal Nuclei;Hippocampus;Autoradiography;Comparative Study;Neural Pathways;Rats;Limbic System;Female;Pregnancy;Brain Mapping;Morphogenesis;Animals;Neurons}, Medline = {80204888}, Month = {3}, Nlm_Id = {0406041}, Number = {1}, Pages = {87-114}, Pubmed = {7381056}, Title = {Development of the hippocampal region in the rat. I. Neurogenesis examined with 3H-thymidine autoradiography}, Uuid = {579E6264-686D-11DA-A4B6-000D9346EC2A}, Volume = {190}, Year = {1980}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901900107}} @article{Bayer:1980a, Author = {Bayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Radiation Tolerance;X-Rays;Cell Differentiation;Limbic System;Female;Rats;Epithelium;Hippocampus;Pregnancy;Brain Mapping;Morphogenesis;Animals}, Medline = {80204878}, Month = {3}, Nlm_Id = {0406041}, Number = {1}, Pages = {115-34}, Pubmed = {7381049}, Title = {Development of the hippocampal region in the rat. II. Morphogenesis during embryonic and early postnatal life}, Uuid = {AD8AE9E6-A3E5-11DA-AB00-000D9346EC2A}, Volume = {190}, Year = {1980}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901900108}} @article{Bayer:1982a, Abstract = {Volumetric estimates of the total number of granule cells in rats 30, 120, 200, and 365 days old increase linearly by approximately 35 to 43 percent between 1 month and 1 year. Total volume of the granular layer also grows linearly during that time. These results demonstrate a numerical increase in a neuronal population during adulthood in the mammalian brain.}, Author = {Bayer, S. A. and Yackel, J. W. and Puri, P. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Science}, Keywords = {B;Rats;Animal;Support, U.S. Gov't, Non-P.H.S.;Hippocampus/cytology/*growth &development;Age Factors;Male}, Number = {4548}, Pages = {890-2.}, Title = {Neurons in the rat dentate gyrus granular layer substantially increase during juvenile and adult life}, Uuid = {9FB6DC5C-67A7-11DA-A4B6-000D9346EC2A}, Volume = {216}, Year = {1982}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7079742}} @article{Bechmann:2000, Abstract = {Entorhinal lesion leads to anterograde degeneration of perforant path fibers in their main hippocampal termination zones. Subsequently, remaining fibers sprout and form new synapses on the denervated dendrites. This degeneration and reorganization is accompanied by sequential changes in glial morphology and function. Within a few hours following the lesion, amoeboid microglia migrate into the zone of denervation. Some hours later, signs of activation can be seen on astrocytes in the zone of denervation, where both cell types proliferate and remain in an activated state for more than two weeks. These activated glial cells might be involved in lesion-induced plasticity in at least two ways: (1) by releasing cytokines and growth factors which regulate layer-specific sprouting and (2) by phagocytosis of axonal debris, because myelin sheaths act as obstacles for sprouting fibers in the central nervous system. Whereas direct evidence for the former is still missing, the latter was investigated using phagocytosis-dependent labeling techniques. Both microglial cells and astrocytes incorporate axonal debris. Phagocytosing microglial cells develop the immune phenotype of antigen-presenting cells, whereas astrocytes strongly express FasL (CD95L), which induces apoptosis of activated lymphocytes. Thus, the interaction of glial cells with immune cells might be another, previously underestimated, aspect of reorganization following entorhinal lesion.}, Author = {Bechmann, I. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0077-8923}, Journal = {Ann N Y Acad Sci}, Keywords = {Brain Diseases;Research Support, Non-U.S. Gov't;Neuroglia;Hippocampus;Neuronal Plasticity;Human;Not relevant;11 Glia;review, tutorial;Humans;Support, Non-U.S. Gov't;Animals;Entorhinal Cortex;review}, Medline = {20369528}, Month = {6}, Nlm_Id = {7506858}, Organization = {Department of Cell and Neurobiology, Humboldt-University Hospital Charit{\'e}, Berlin, Germany.}, Pages = {192-206}, Pubmed = {10911875}, Title = {Involvement of non-neuronal cells in entorhinal-hippocampal reorganization following lesions}, Uuid = {BCB4B0B6-B62E-486B-8048-F318F2BD32EC}, Volume = {911}, Year = {2000}, url = {papers/Bechmann_AnnNYAcadSci2000.pdf}} @article{Bechmann:2001, Abstract = {Virchow-Robin's perivascular spaces lie between the basement membrane around pericytes and the basement membrane at the surface of the glia limitans of the brain vessels. They are directly connected to the subpial space and harbour a population of cells distinct from pericytes, perivascular microglia and other cells within perivascular spaces (e.g. T cells and mast cells) in their ability to quickly phagocytose particles from the cerebrospinal fluid (CSF). Morphology, function, and cell surface proteins of these perivascular cells suggest an origin from the monocyte/macrophage lineage. It is currently unclear to what extent these brain perivascular cells represent a resident population of histiocytes or undergo continuous supplementation from blood monocytes. Using transplants of green-fluorescent-protein (GFP)-transfected bone marrow cells, we therefore investigated the replacement of perivascular cells by blood-borne macrophages in adult mice. GFP-positive cells in the perivascular spaces were found as early as 2 weeks post transplantation. The substitution of host perivascular cells by donor-derived macrophages was then evaluated using immunocytochemistry and intraventricular injection of hydrophilic rhodamine-fluorescent tracers. Such tracers diffuse along perivascular spaces and are subsequently phagocytosed by perivascular cells leading to stable phagocytosis-dependent labelling. Thus, the population of newly immigrated macrophages could be related to the total number of perivascular macrophages. This approach revealed a continuous increase of donor-derived perivascular cells. At 14 weeks post transplantation, all perivascular cells were donor-derived. These data show that brain perivascular cells are a population of migratory macrophages and not resident histiocytes.}, Author = {Bechmann, I. and Priller, J. and Kovac, A. and B{\"o}ntert, M. and Wehner, T. and Klett, F. F. and Bohsung, J. and Stuschke, M. and Dirnagl, U. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Blood Vessels;Fluorescent Dyes;Rhodamines;Cell Differentiation;Animals;Macrophages;Pericytes;Dextrans;Bone Marrow Transplantation;Brain;Indicators and Reagents;Cell Count;Cell Movement;Mice, Inbred C57BL;11 Glia;Chemotaxis, Leukocyte;Green Fluorescent Proteins;Pia Mater;Immune System;Bone Marrow Cells;Cell Lineage;Mice;Immunohistochemistry;Luminescent Proteins;Biotin;Research Support, Non-U.S. Gov't}, Medline = {21850280}, Month = {11}, Nlm_Id = {8918110}, Number = {10}, Organization = {Department of Cell and Neurobiology, Institute of Anatomy, Humboldt-University Hospital Charit{\'e}, Schumannstrasse 20/21, D-10098 Berlin, Germany. ingo.bechmann\@charite.de}, Pages = {1651-8}, Pii = {1793}, Pubmed = {11860459}, Title = {Immune surveillance of mouse brain perivascular spaces by blood-borne macrophages}, Uuid = {B96B461E-B550-4DF8-819C-10F012B25DF9}, Volume = {14}, Year = {2001}, url = {papers/Bechmann_EurJNeurosci2001.pdf}} @article{Bechmann:2001a, Abstract = {Brain perivascular spaces harbor a population of cells which exhibit high phagocytic capacity. Therefore, these cells can be labeled by intraventricular injection of tracers. Such perivascular cells at the interface between blood and brain are believed to belong to the monocyte/macrophage lineage and to be involved in antigen presentation. Currently, it is unclear whether these cells undergo a continuous turnover by entering and leaving the bloodstream. Using bone-marrow-chimeric animals, migration of donor macrophages into brain perivascular spaces has been reported. On the other hand, following intracerebral injection of india ink into nontransplanted animals, ink-labeled perivascular cells were still found 2 years after injection, suggesting a high stability of this cell pool. Thus, the turnover of perivascular cells observed in chimeras might be a result of bone marrow transplantation rather than a physiological occurrence. To address this issue, we monitored de novo invasion of macrophages into perivascular spaces of apparently healthy adult rats by applying techniques other than bone marrow transplantation, (i) consecutive injections of different tracers and (ii) ex vivo isolation of macrophages from the blood, cell labeling, and reinjection into the same animal to avoid MHC mismatch. Both approaches revealed vivid de novo invasion of macrophages into perivascular spaces, but not into brain parenchyma, rendering untenable the concept of perivascular cells forming a stable population of macrophages in the brain. Thus, brain perivascular spaces are under permanent immune surveillance of blood borne macrophages in normal adult rats.}, Author = {Bechmann, I. and Kwidzinski, E. and Kovac, A. D. and Simb{\"u}rger, E. and Horvath, T. and Gimsa, U. and Dirnagl, U. and Priller, J. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Research Support, Non-U.S. Gov't;Basement Membrane;Rats;Rats, Wistar;Fluorescent Dyes;11 Glia;Macrophages;Animals;Oligodendroglia;Brain;Cell Movement}, Medline = {21159780}, Month = {4}, Nlm_Id = {0370712}, Number = {2}, Organization = {Institute of Anatomy, Humboldt-University Hospital Charit{\'e}, Berlin, Germany. ingo.bechmann\@charite.de}, Pages = {242-9}, Pii = {S0014488600976180}, Pubmed = {11259112}, Title = {Turnover of rat brain perivascular cells}, Uuid = {8481D47F-D3B7-11D9-A0E9-000D9346EC2A}, Volume = {168}, Year = {2001}, url = {papers/Bechmann_ExpNeurol2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.2000.7618}} @article{Bechmann:2005, Abstract = {In this study, we demonstrate the infiltration of blood-derived monocytic cells and their morphologic transformation into microglia in zones of acute, anterograde (Wallerian) axonal degeneration induced by entorhinal cortex lesion (ECL). ECL was performed in mice which had received green fluorescent protein (GFP)-transduced bone marrow grafts allowing identification of blood-derived elements within the brain. While in the unlesioned hemisphere GFP(+) cells were restricted to perivascular and leptomeningeal sites, many round fluorescent cells appeared in hippocampal zones of axonal degeneration at 24 h post lesion (hpl). Within 72 hpl, these GFP(+) cells acquired ramified, microglia-like morphologies, which persisted for at least 7 days post ECL. Differentiation of GFP(+) cells into glial fibrillary acidic protein (GFAP)(+) astrocytes was never observed. To exclude that this recruitment is an artifact of irradiation or bone marrow transplantation, the fluorescent cell tracker 6-carboxylfluorescein diacetate (CFDA) was injected into spleens of normal mice 1 day before ECL. Again, fluorescent cells appeared at the lesion site and along the layers of axonal degeneration at 48 hpl and CFDA+/MAC-1(+), cells exhibited amoeboid and ramified morphologies. Thus, blood-derived cells infiltrate not only the site of mechanical lesion, but also the layers of anterograde axonal degeneration, where they readily transform into microglia-like elements. A role for infiltrating leukocytes in facilitating or modulating postlesional plasticity, e.g., by phagocytosis of growth-inhibiting myelin should now be considered. Moreover, monocytic cells may serve as vehicles to transport therapeutic substances such as neurotrophic factors or caspase inhibitors to zones of axonal degeneration.}, Author = {Bechmann, and Goldmann, and Kovac, and Kwidzinski, and Simb{\"u}rger, and Naftolin, and Dirnagl, and Nitsch, and Priller,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:17 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {8804484}, Number = {6}, Pages = {647-9}, Pii = {04-2599fje}, Pubmed = {15671154}, Title = {Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia}, Uuid = {2598CBB2-F3D0-40DD-BB0C-9C32AE3CC447}, Volume = {19}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.04-2599fje}} @article{Bechmann:1997, Abstract = {Entorhinal lesion leads to anterograde degeneration of perforant path fibers in their main termination zone in the outer molecular layers of the dentate gyrus. Concomitantly, astrocytes become hypertrophic, and microglial cells alter their phenotype, suggesting participation in anterograde degeneration. This study analyzes the involvement of these lesion-induced activated glial cells in the process of phagocytosis of degenerated axonal debris. We established a phagocytosis-dependent labeling technique that allows for direct and simultaneous visualization of both labeled incorporated axonal debris and incorporating glial cells. Stereotaxic application of small crystals of the biotin- and rhodamine-conjugated dextran amine Mini Ruby (MR) into the entorhinal cortex led to strong and stable axonal staining of perforant path axons. Following entorhinal lesion, labeled terminals and fibers condensed and formed small granules. Incorporation of these rhodamine-fluorescent granules resulted in a phagocytosis-dependent cell labeling. During the first 3 days, we were able to identify these cells as microglia by using double-fluorescence and confocal microscopy. The first unequivocally double-labeled astrocytes were found 6 days post lesion (dpl). Whereas in all stages a subpopulation of microglial cells remained devoid of MR-labeled granules, all astrocytes in the middle molecular layer were double-labeled after long survival times (20 dpl). On the ultrastructural level, labeled granules appeared to be perforant path axons containing the tracer. Both terminals and myelinated fibers could be seen inside the cytoplasm of microglial cells and astrocytes. Thus, anterograde degeneration is a sufficient stimulus to induce axon incorporation by both astrocytes and a subpopulation of microglial cells.}, Author = {Bechmann, I. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Fluorescent Dyes;Rhodamines;Nerve Degeneration;Astrocytes;Animals;Phagocytosis;Rats;Dextrans;Microglia;Female;Entorhinal Cortex;Axons;Hippocampus;Rats, Wistar;Not relevant;Microscopy, Fluorescence;11 Glia;Male;Axonal Transport;Support, Non-U.S. Gov't;Nerve Fibers;Biotin;Research Support, Non-U.S. Gov't}, Medline = {97323109}, Month = {6}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Cell and Neurobiology, Humboldt University Hospital Charit{\'e}, Berlin, Germany.}, Pages = {145-54}, Pii = {10.1002/(SICI)1098-1136(199706)20:2<145::AID-GLIA6>3.0.CO;2-8}, Pubmed = {9179599}, Title = {Astrocytes and microglial cells incorporate degenerating fibers following entorhinal lesion: a light, confocal, and electron microscopical study using a phagocytosis-dependent labeling technique}, Uuid = {03618D06-1D73-4A59-B36E-946EB165A511}, Volume = {20}, Year = {1997}} @article{Bechmann:1997a, Abstract = {Retrograde and anterograde degeneration have been reported to be sufficient stimuli to activate glial cells, which, in turn, are involved in phagocytosis of degenerating material. Here we describe a double-fluorescence technique which allows for direct and simultaneous visualization of both labeled incorporated axonal debris and incorporating glial cells in the course of anterograde degeneration. Stereotaxic application of small crystals of biotinylated and tetramethylrhodamine (TRITC)-conjugated dextran amine Mini Ruby into the medial entorhinal cortex resulted in a stable rhodamine fluorescence confined to fibers and terminals in the middle molecular layer of the dentate gyrus, the stratum lacunosum-moleculare, and the crossed temporo-hippocampal pathway. Subsequent stereotaxic lesion of the entorhinal cortex induced transformation of rhodamine-fluorescent fibers and terminals into small granules. Incorporation of these granules by microglial cells [labeled by fluorescein isothiocyanate (FITC)-coupled Bandeiraea simplicifolia isolectin B4] or astrocytes (labeled by FITC-coupled glial fibrillary acidic protein antibodies) resulted in phagocytosis-dependent labeling of these non-neuronal cells, which could be identified by double-fluorescence microscopy. Electron microscopical analysis revealed that, following lesion, the tracer remained confined to entorhinal axons which were found to be incorporated by glial cells. Our data show that TRITC- and biotin-conjugated dextran amines are versatile tracers leading to Phaseolus vulgaris leucoagglutinin-like axonal staining. Lesion-induced phagocytosis of anterogradely degenerating axons by immunocytochemically identified glial cells can be directly observed by this technique on the light and electron microscopical levels.}, Author = {Bechmann, I. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0948-6143}, Journal = {Histochem Cell Biol}, Keywords = {Rhodamines;Research Support, Non-U.S. Gov't;Neuroglia;Nerve Degeneration;Female;Rats;Phagocytes;Immunohistochemistry;Rats, Wistar;Fluorescent Dyes;11 Glia;Microscopy, Fluorescence;Biotin;Microscopy, Immunoelectron;Male;Animals;Axons}, Medline = {97352048}, Month = {5}, Nlm_Id = {9506663}, Number = {5}, Organization = {Humboldt University Clinic Charit{\'e}, Department of Cell and Neurobiology, Berlin, Germany.}, Pages = {391-7}, Pubmed = {9208330}, Title = {Identification of phagocytic glial cells after lesion-induced anterograde degeneration using double-fluorescence labeling: combination of axonal tracing and lectin or immunostaining}, Uuid = {1457F59F-FC5F-4C9A-865A-250CE842A6FF}, Volume = {107}, Year = {1997}} @article{Bechmann:2001b, Abstract = {In contrast to other organs where the tissue is capable of replacing lost cells and thus regaining tissue function, immune cell recruitment and activation is suppressed in the CNS in order to minimize secondary damage after lesion. This state of immune privilege has its cost because the injured tissue cannot fully benefit from growth-promoting effects accompanying inflammatory responses. These responses include phagocytosis of growth-inhibiting myelin debris by cells of the innate immune system and the recently described protection of surviving fibers by myelin-specifie T cells of the adaptive immune system. While the signals suppressing macrophage functions in the CNS are yet to be defined, it seems that help from T cells is diminished by apoptosis-induction via death-inducing ligands. Indeed, the death ligand CD95L (FasL, APO 1 L) is constitutively found on neurons, microglia and astrocytes. Its upregulation on astrocytes during axonal degeneration in the hippocampus after entorhinal lesion is accompanied by the appearance of apoptotic leukocytes. T cells also express CD95L and TNF-related apoptosis- inducing ligand (TRAIL), and the presence of CD95 (Fas, APOI) and TRAIL-receptors renders brain cells putative targets of T cell-induced apoptosis. Thus, blockade of death ligands could be helpful by simultaneously enhancing T cell survival and blocking T cell-mediated brain cell death. This is only one example of how boosting helpful immune cell functions and abrogating their destructive effects might help to overcome the brain's failure to regenerate after axonal lesions.}, Author = {Bechmann, I. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0922-6028}, Journal = {Restor Neurol Neurosci}, Keywords = {review literature;Central Nervous System;Research Support, Non-U.S. Gov't;Human;Neuronal Plasticity;Neuroimmunomodulation;Not relevant;11 Glia;Animals;Humans;Central Nervous System Diseases;review;Support, Non-U.S. Gov't}, Medline = {22077803}, Nlm_Id = {9005499}, Number = {3-4}, Organization = {Institute of Anatomy, Department Cell and Neurobiology, Humboldt-University Hospital Charit{\'e}, 10098 Berlin, Germany.}, Pages = {189-98}, Pubmed = {12082221}, Title = {Plasticity following lesion: help and harm from the immune system}, Uuid = {F86530C0-3FA3-44BD-9A4E-9F302134CC37}, Volume = {19}, Year = {2001}} @article{Beck:2003, Abstract = {Bone marrow-derived cells participate in remodeling processes of many ischemia-associated diseases, which has raised hopes for the use of bone marrow as a source for cell-based therapeutic approaches. To study the participation of bone marrow-derived cells in a stroke model, bone marrow from C57BL/6-TgN(ACTbEGFP)1Osb mice that express green fluorescent protein (GFP) in all cells was transplanted into C57BL/6J mice. The recipient mice underwent permanent occlusion of the middle cerebral artery, and bone marrow-derived cells were tracked by fluorescence. The authors investigated the involvement of bone marrow-derived cells in repair processes 6 weeks and 6 months after infarction. Six weeks after occlusion of the artery, more than 90\%of the GFP-positive cells in the infarct border zone were microglial cells. Very few GFP-positive cells expressed endothelial markers in the infarct/infarct border zone, and no bone marrow-derived cells transdifferentiated into astrocytes, neurons, or oligodendroglial cells at all time points investigated. The results indicate the need for additional experimental studies to determine whether therapeutic application of nonselected bone marrow will replenish brain cells beyond an increase in microglial engraftment.}, Author = {Beck, Heike and Voswinckel, Robert and Wagner, Shawn and Ziegelhoeffer, Tibor and Heil, Matthias and Helisch, Armin and Schaper, Wolfgang and Acker, Till and Hatzopoulos, Antonis K. and Plate, Karl H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0271-678X}, Journal = {J Cereb Blood Flow Metab}, Keywords = {Research Support, Non-U.S. Gov't;Cell Differentiation;Animals;Infarction, Middle Cerebral Artery;Bone Marrow Transplantation;Microglia;2',3'-Cyclic-Nucleotide Phosphodiesterases;Indicators and Reagents;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Male;Bone Marrow Cells;Choroid Plexus;Age Factors;Mice;Luminescent Proteins;Biological Markers;Lectins;von Willebrand Factor;Glial Fibrillary Acidic Protein}, Medline = {22681133}, Month = {6}, Nlm_Id = {8112566}, Number = {6}, Organization = {GSF-Research Center for Environment &Health, Institute for Clinical Molecular Biology and Tumor Genetics, Munich, Germany. Heike.Beck\@gsf.de}, Pages = {709-17}, Pubmed = {12796719}, Title = {Participation of bone marrow-derived cells in long-term repair processes after experimental stroke}, Uuid = {D455721A-9CEF-4BCA-9994-4B8B9EA8BC59}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1097/01.WCB.0000065940.18332.8D}} @article{Beck:1995, Abstract = {Homozygous Igf1-/- mice at 2 months of age had reduced brain weights, with reductions evenly affecting all major brain areas. The gross morphology of the CNS was normal, but the size of white matter structures in brain and spinal cord was strongly reduced, owing to decreased numbers of axons and oligodendrocytes. Myelinated axons were more strongly reduced in number than unmyelinated axons. The volume of the dentate gyrus granule cell layer was reduced in excess of the decrease in brain weight. Among populations of calcium-binding protein-containing neurons, there was a selective reduction in the number of striatal parvalbumin-containing cells. Numbers of mesencephalic dopaminergic neurons, striatal and basal forebrain cholinergic neurons, and spinal cord motoneurons were unaffected. Cerebellar morphology was unaltered. Our findings suggest cell type- and region-specific functions for IGF-I and emphasize prominent roles in axon growth and maturation in CNS myelination.}, Author = {Beck, K. D. and Powell-Braxton, L. and Widmer, H. R. and Valverde, J. and Hefti, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Glial Fibrillary Acidic Protein;10 Development;10 Hippocampus;Animals;Myelin Sheath;Astrocytes;Corpus Striatum;Research Support, U.S. Gov't, Non-P.H.S.;Brain;Mutation;Cell Count;Hippocampus;Mice, Inbred C57BL;Axons;Calcium-Binding Protein, Vitamin D-Dependent;Spinal Cord;Research Support, U.S. Gov't, P.H.S.;Parvalbumins;Neurons;Organ Size;Mice;Insulin-Like Growth Factor I;Research Support, Non-U.S. Gov't}, Medline = {95234311}, Month = {4}, Nlm_Id = {8809320}, Number = {4}, Organization = {Department of Neuroscience, Genentech, Incorporated, South San Francisco, California 94080, USA.}, Pages = {717-30}, Pubmed = {7718235}, Title = {Igf1 gene disruption results in reduced brain size, CNS hypomyelination, and loss of hippocampal granule and striatal parvalbumin-containing neurons}, Uuid = {46334EB3-F160-49A1-A5F2-DF23B1A727B1}, Volume = {14}, Year = {1995}} @article{Becker:2001, Abstract = {We analyzed pathway choices of regenerating, mostly supraspinal, descending axons in the spinal cord of adult zebrafish and the cellular changes in the spinal cord caudal to a lesion site after complete spinal transection. Anterograde tracing (by application of the tracer rostral to the spinal lesion site) showed that significantly more descending axons (74\%) regenerated in the spinal gray matter of the caudal spinal cord than would be expected from random growth. Retrograde tracing (by application of the tracer caudal to the spinal lesion site) showed that, rostral to the lesion, most of these axons (80\%) extended into the major white matter tracts. Thus, ventral descending tracts often were devoid of labeled axons caudal to a spinal lesion but contained many axons rostral to the lesion in the same animals, indicating a pathway switch of descending axons from the white matter to the gray matter. Ascending axons of spinal neurons were not observed regrowing to the rostral tracer application site; therefore, they most likely did not contribute to the axonal populations analyzed. A macrophage/microglia response within 2 days of spinal cord transection, along with phagocytosis of myelin, was observed caudal to the transection by immunohistochemistry and electron microscopy. Nevertheless, caudal to the lesion, descending tracts in the white matter were filled with myelin debris during the time of axonal regrowth, at least up to 6 weeks postlesion. We suggest that the spontaneous regeneration of axons of supraspinal origin after spinal cord transection in adult zebrafish may be due in part to the axons' ability to negotiate novel pathways in the spinal cord gray matter.}, Author = {Becker, T. and Becker, C. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Zebrafish;Neurons, Efferent;Spinal Cord Injuries;Nerve Regeneration;Not relevant;11 Glia;Microglia;Macrophages;Spinal Cord;Neurons, Afferent;Age Factors;Support, Non-U.S. Gov't;Animals;Axons}, Medline = {21179351}, Month = {4}, Nlm_Id = {0406041}, Number = {1}, Organization = {Zentrum f{\"u}r Molekulare Neurobiologie Hamburg, Universit{\"a}t Hamburg, Martinistr. 52, D-20246 Hamburg, Germany. tcbecker\@zmnh.uni-hamburg.de}, Pages = {131-47}, Pubmed = {11283955}, Title = {Regenerating descending axons preferentially reroute to the gray matter in the presence of a general macrophage/microglial reaction caudal to a spinal transection in adult zebrafish}, Uuid = {3BCC4454-72E3-405A-9F82-C37AFF578B56}, Volume = {433}, Year = {2001}} @article{Becq:2005, Abstract = {In the present article we investigated the properties of CA1 and dentate gyrus cell precursors in adult rodents both in vivo and in vitro. Cell proliferation in situ was investigated by rating the number of cells incorporating BrdU after kainate-induced seizures. CA1 precursors displayed a greater proliferation capacity than dentate gyrus precursors. The majority of BrdU-labeled cells in CA1 expressed Nestin and Mash-1, two markers of neural precursors. BrdU-positive cells in the dentate gyrus expressed Nestin, but only a few expressed Mash-1. In animals pretreated with the antimitotic azacytidine, the capacity of kainate to enhance the proliferation was higher in CA1 than in the dentate gyrus. Differences in intrinsic progenitor cell activity could underlie these different expansion capacities. Thus, we compared the renewal- expansion and multipotency of dentate gyrus and CA1 precursors isolated in vitro. We found that the dissected CA1 region, including the periventricular zone, is enriched in neurosphere-forming cells (presumed stem cells), which respond to either EGF or FGF-2. Dentate gyrus contains fewer neurosphere-forming cells and none that respond to FGF-2 alone. Neurospheres generated from CA1 were multipotent and produced neurons, astrocytes, and oligodendrocytes, while dentate gyrus neurospheres mostly produced glial cells. The analysis of the effects of EGF on organotypic cultures of hippocampal slices depicted similar features: BrdU and Nestin immunoreactivities increased after EGF treatment in CA1 but not in the dentate gyrus. These results suggest that CA1 precursors are more stem-cell-like than granule cell precursors, which may represent a more restricted precursor cell.}, Author = {Becq, H. and Jorquera, I. and Ben-Ari, Y. and Weiss, S. and Represa, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Cell Differentiation;Phosphopyruvate Hydratase;24 Pubmed search results 2008;Immunohistochemistry;Kainic Acid;Animals;Cells, Cultured;Epidermal Growth Factor;Hippocampus;In Vitro;Cell Count;Transcription Factors;Fibroblast Growth Factor 2;Basic Helix-Loop-Helix Transcription Factors;Azacitidine;Statistics, Nonparametric;Analysis of Variance;Intermediate Filament Proteins;Drug Interactions;Excitatory Amino Acid Agonists;Bromodeoxyuridine;21 Epilepsy;DNA-Binding Proteins;Comparative Study;Enzyme Inhibitors;Time Factors;Dose-Response Relationship, Drug;Stem Cells;21 Neurophysiology;Cell Proliferation;Mice;Research Support, Non-U.S. Gov't;Neurons;Nerve Tissue Proteins;Dentate Gyrus}, Month = {2}, Nlm_Id = {0213640}, Number = {2}, Organization = {INMED/INSERM U29, Marseille, France.}, Pages = {243-61}, Pubmed = {15459894}, Title = {Differential properties of dentate gyrus and CA1 neural precursors}, Uuid = {2CE64E7C-17EB-4B3E-B606-83B4ED6AB637}, Volume = {62}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.20089}} @article{Bedard:2004, Abstract = {The subventricular zone (SVZ) is known to be the major source of neural stem cells in the adult brain. In rodents and nonhuman primates, many neuroblasts generated in the SVZ migrate in chains along the rostral migratory stream (RMS) to populate the olfactory bulb (OB) with new granular and periglomerular interneurons. In order to know if such a phenomenon exists in the adult human brain, we applied single and double immunostaining procedures to olfactory bulbs obtained following brain necropsy in normal adult human subjects. Double immunofluorescence labelling with a confocal microscope served to visualize cells that express markers of proliferation and immature neuronal state as well as markers that are specific to olfactory interneurons. Newborn cells that express cell cycle proteins [Ki-67, proliferating cell nuclear antigen (PCNA)] were detected in the granular and glomerular layers (GLs) of the human olfactory bulb; these cells coexpressed markers of immature neuronal state, such as Doublecortin (DCX), NeuroD and Nestin. Numerous differentiating cells expressed molecular markers of early committed neurons [beta-tubulin class III (TuJ1)] and were also immunoreactive for glutamic acid decarboxylase (GAD), a marker of GABAergic neurons, or tyrosine hydroxylase (TH), a marker of dopaminergic neurons. Other early committed neurons expressed the calcium-binding proteins calretinin (CR) or parvalbumin (PV). These results provide strong evidence for the existence of adult neurogenesis in the human olfactory system. Despite its relatively small size compared to that in rodents and nonhuman primates, the olfactory bulb in humans appears to be populated, throughout life, by new granular and periglomerular neurons that express a wide variety of chemical phenotypes. 0165-3806 Journal Article}, Author = {Bedard, A. and Parent, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {A, B pdf;01 Adult neurogenesis general}, Number = {1-2}, Organization = {Centre de recherche Universite Laval Robert-Giffard, 2601, de la Canardiere, Local F-6500, Beauport, Quebec, Canada G1J 2G3.}, Pages = {159-68}, Title = {Evidence of newly generated neurons in the human olfactory bulb}, Uuid = {35520F15-A307-4859-A8BA-960EBF838577}, Volume = {151}, Year = {2004}, url = {papers/Bedard_BrainResDevBrainRes2004.pdf}} @article{Beech:2004, Abstract = {The subventricular zone (SVZ) is a major neurogenic region in the adult brain. Cells from the SVZ give rise to two populations of olfactory bulb interneurons: the granule cells and periglomerular (PG) cells. Currently, little is known about the signaling pathways that direct these newly generated neurons to become either granule or PG neurons. In the present study, we used the nestin promoter and enhancer to direct expression of the tetracycline transactivator (tTA). We generated two independent strains of nestin-tTA transgenic animals and crossed founder mice from both lines to mice containing a tetracycline-regulated transgene (mCREB) whose expression served as a marker for the activity of the nestin-tTA transgene. mCREB expression occurred in a subset of proliferating cells in the SVZ and rostral migratory stream in both lines. Surprisingly, in both lines of nestin-tTA mice transgene expression in the olfactory bulb was limited to PG neurons and was absent from granule cells, suggesting that this nestin promoter construct differentiates between the two interneuronal populations. Transgene expression occurred in several subtypes of PG neurons, including those expressing calretinin, calbindin, GAD67, and tyrosine hydroxylase. These results suggest that a unique subset of SVZ precursor cells gives rise to PG, and not granule cells. The ability to express different transgenes within this subpopulation of neuronal precursors provides a powerful system to define the signals regulating the differentiation and survival of adult-generated neurons in the olfactory bulb.}, Author = {Beech, Robert D. and Cleary, Muriel A. and Treloar, Helen B. and Eisch, Amelia J. and Harrist, Alexia V. and Zhong, Weimin and Greer, Charles A. and Duman, Ronald S. and Picciotto, Marina R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Transgenes;13 Olfactory bulb anatomy;DNA-Binding Protein, Cyclic AMP-Responsive;03 Adult neurogenesis progenitor source;Comparative Study;Nerve Tissue Proteins;Gene Expression Regulation;Stem Cells;Promoter Regions (Genetics);Mice, Transgenic;Support, U.S. Gov't, P.H.S.;Olfactory Bulb;Animals;Mice;Support, Non-U.S. Gov't;Neurons;Intermediate Filament Proteins}, Month = {7}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor, New Haven, CT 06508, USA. robert.beech\@yale.edu}, Pages = {128-41}, Pubmed = {15176089}, Title = {Nestin promoter/enhancer directs transgene expression to precursors of adult generated periglomerular neurons}, Uuid = {631DD709-3120-4135-B2C0-5ACA90D3F00E}, Volume = {475}, Year = {2004}, url = {papers/Beech_JCompNeurol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20179}} @article{Beg:2006, Author = {Beg, Asim A. and Scheiffele, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {10 Development;Calcium Signaling;Animals;Synapses;comment;Rats;Phosphorylation;Brain;Hippocampus;RNA Interference;Calcium;10 circuit formation;Small Ubiquitin-Related Modifier Proteins;Myogenic Regulatory Factors;Dendrites;Neurons;Cerebellum;24 Pubmed search results 2008;Transcription, Genetic}, Month = {2}, Nlm_Id = {0404511}, Number = {5763}, Organization = {Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA. ab2516\@columbia.edu}, Pages = {962-3}, Pii = {311/5763/962}, Pubmed = {16484483}, Title = {Neuroscience. SUMO wrestles the synapse}, Uuid = {01D56082-FD9D-40A8-8EFD-73D7490FB897}, Volume = {311}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1124541}} @article{Beggs:2003, Abstract = {Targeted deletion of focal adhesion kinase (fak) in the developing dorsal forebrain resulted in local disruptions of the cortical basement membrane located between the neuroepithelium and pia-meninges. At disruption sites, clusters of neurons invaded the marginal zone. Retraction of radial glial endfeet, midline fusion of brain hemispheres, and gliosis also occurred, similar to type II cobblestone lissencephaly as seen in congenital muscular dystrophy. Interestingly, targeted deletion of fak in neurons alone did not result in cortical ectopias, indicating that fak deletion from glia is required for neuronal mislocalization. Unexpectedly, fak deletion specifically from meningeal fibroblasts elicited similar cortical ectopias in vivo and altered laminin organization in vitro. These observations provide compelling evidence that FAK plays a key signaling role in cortical basement membrane assembly and/or remodeling. In addition, FAK is required within neurons during development because neuron-specific fak deletion alters dendritic morphology in the absence of lamination defects.}, Author = {Beggs, Hilary E. and Schahin-Reed, Dorreyah and Zang, Keling and Goebbels, Sandra and Nave, Klaus Armin and Gorski, Jessica and Jones, Kevin R. and Sretavan, David and Reichardt, Louis F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Mice;Focal Adhesion Protein-Tyrosine Kinases;Dystroglycans;Precipitin Tests;Cells, Cultured;Carrier Proteins;Staining and Labeling;Microtubule-Associated Proteins;DNA-Binding Proteins;Mice, Knockout;Protein-Tyrosine Kinase;Transcription Factors;Cerebral Cortex;Fibroblasts;Calcium-Binding Protein, Vitamin D-Dependent;Disease Models, Animal;Basement Membrane;Research Support, U.S. Gov't, P.H.S.;src-Family Kinases;Embryo;Mutation;Neurons;Serine Endopeptidases;Phosphotyrosine;Bacterial Proteins;Immunohistochemistry;Heterozygote;Extracellular Matrix Proteins;Microscopy, Electron;Phosphopyruvate Hydratase;Cytoskeletal Proteins;Comparative Study;Glial Fibrillary Acidic Protein;Astrocytes;Otx Transcription Factors;Lamins;10 Development;Research Support, Non-U.S. Gov't;Animals;Blotting, Western;Infection;Dura Mater;Focal Adhesion Kinase 1;Homeodomain Proteins;Membrane Glycoproteins;Silver Staining;Muscular Dystrophies;Cell Adhesion Molecules, Neuronal;10 Hippocampus;Nerve Tissue Proteins}, Month = {10}, Nlm_Id = {8809320}, Number = {3}, Organization = {Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, CA 94143, USA. hbeggs\@itsa.ucsf.edu}, Pages = {501-14}, Pii = {S0896627303006664}, Pubmed = {14642275}, Title = {FAK deficiency in cells contributing to the basal lamina results in cortical abnormalities resembling congenital muscular dystrophies}, Uuid = {82C60539-F56B-4FCE-A2BF-1921897C9641}, Volume = {40}, Year = {2003}} @article{Behr:1998, Abstract = {Extracellular recordings were performed in combined hippocampal-entorhinal cortex (HC-EC) slices obtained from control and commissural kindled rats to investigate the propagation of epileptiform activity from the entorhinal cortex (EC) to the hippocampus (HC) after chronic epilepsy. Lowering extracellular Mg2+ concentration in control slices induced epileptiform activity consisting of spontaneous epileptiform bursts in area CA3 and of electrographic seizures in the EC. In contrast, the CA3 region of HC-EC slices obtained from kindled rats displayed significantly longer lasting epileptiform bursts and electrographic seizures. The electrographic seizures that were absent in controls propagated from the EC because disconnecting the HC from the EC stopped their occurrence in the CA3, whereas epileptiform bursts persisted with an unaltered pattern and frequency. Thus the area CA3 is affected by kindling and contributes to the spread of epileptiform activity within the EC-HC complex. We developed a method to induce focal epileptiform activity in the EC by locally perfusing the gamma-aminobutyric acid-A (GABA) antagonist bicuculline (50 mM) in 10 mM KCl containing artificial cerebrospinal fluid. This method enabled us to investigate the propagation of epileptiform discharges from the disinhibited EC to the DG without affecting the DG with the epileptogenic medium. We show here that kindling facilitates the propagation of epileptiform activity through the DG. These data are consistent with the normal function of the DG as a filter limiting the spread of epileptiform activity within the HC-EC complex. This gating mechanism breaks down after chronic epilepsy induced by kindling.}, Author = {Behr, J. and Lyson, K. J. and Mody, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Epilepsy;Research Support, Non-U.S. Gov't;21 Neurophysiology;Bicuculline;Rats;Research Support, U.S. Gov't, P.H.S.;Dentate Gyrus;Rats, Wistar;Kindling (Neurology);In Vitro;Chronic Disease;Evoked Potentials;Animals;Entorhinal Cortex;24 Pubmed search results 2008;GABA Antagonists;21 Epilepsy}, Medline = {98204950}, Month = {4}, Nlm_Id = {0375404}, Number = {4}, Organization = {Department of Neurology, Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.}, Pages = {1726-32}, Pubmed = {9535942}, Title = {Enhanced propagation of epileptiform activity through the kindled dentate gyrus}, Uuid = {2E217B37-2A74-413A-96B2-E028EBC30BC2}, Volume = {79}, Year = {1998}} @article{Beierlein:2002, Abstract = {Sensory information reaches the cortex via thalamocortical (TC) synapses in layer 4. Thalamic relay neurons that mediate information flow to cortex operate in two distinct modes, tonic and burst firing. Burst firing has been implicated in enhancing reliability of information flow between individual neurons. However, little is known about how local networks of neocortical neurons respond to different temporal patterns of TC activity. We studied cortical activity patterns evoked by stimulating TC afferents at different frequencies, using a combination of electrophysiology and calcium imaging in TC slices that allowed for the reconstruction of spatiotemporal activity with single-cell resolution. Stimulation of TC axons at low frequencies triggered action potentials in only a small number of layer 4 neurons. In contrast, brief high-frequency stimulus trains triggered widespread recurrent activity in populations of neurons in layer 4 and then spread into adjacent layers 2/3 and 5. Recurrent activity had a clear threshold, typically lasted 300 msec, and could be evoked repetitively at frequencies up to 0.5 Hz. Moreover, the spatial extent of recurrent activity was controlled by the TC pattern of activity. Recurrent activity triggered within the highly interconnected networks of layer 4 might act to selectively amplify and redistribute transient high-frequency TC inputs, filter out low-frequency inputs, and temporarily preserve a record of past sensory activity.}, Author = {Beierlein, Michael and Fall, Christopher P. and Rinzel, John and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Electric Stimulation;Animals;research support, u.s. gov't, p.h.s. ;Neocortex;Synaptic Transmission;Patch-Clamp Techniques;in vitro ;Reaction Time;Mice, Inbred C57BL;Calcium;research support, non-u.s. gov't ;Nerve Net;Action Potentials;Thalamus;21 Neurophysiology;Sensory Thresholds;Somatosensory Cortex;Mice;Interneurons;24 Pubmed search results 2008;Neural Inhibition;Excitatory Postsynaptic Potentials}, Month = {11}, Nlm_Id = {8102140}, Number = {22}, Organization = {Department of Biological Sciences, Columbia University, New York, New York 10027, USA. mbeierlein\@hms.harvard.edu}, Pages = {9885-94}, Pii = {22/22/9885}, Pubmed = {12427845}, Title = {Thalamocortical bursts trigger recurrent activity in neocortical networks: layer 4 as a frequency-dependent gate}, Uuid = {624DFFAF-11EF-4932-8F7E-AB87490FF6F0}, Volume = {22}, Year = {2002}, url = {papers/Beierlein_JNeurosci2002.pdf}} @article{Beierlein:2006, Abstract = {Neurons release endocannabinoids from their dendrites to trigger changes in the probability of transmitter release. Although such retrograde signaling has been described for principal neurons, such as hippocampal pyramidal cells and cerebellar Purkinje cells (PCs), it has not been demonstrated for local interneurons. Here we tested whether inhibitory interneurons in the cerebellum, stellate cells (SCs) and basket cells, regulate the strength of parallel fiber (PF) synapses by releasing endocannabinoids. We found that depolarization-induced suppression of excitation (DSE) is present in both SCs and basket cells. The properties of retrograde inhibition were examined more thoroughly for SCs. Both DSE and synaptically evoked suppression of excitation (SSE) triggered with brief PF bursts require elevations of postsynaptic calcium, are blocked by a type 1 cannabinoid receptor (CB1R) antagonist, and are absent in mice lacking the CB1R. SSE for SCs is similar to that described previously for PCs in that it is prevented by BAPTA and DAG lipase inhibitors in the recording pipette; however, unlike in PCs, NMDA receptors (NMDARs) play an important role in SSE for SCs. Although SCs express CB1Rs postsynaptically, neither high-frequency firing of SCs nor PF bursts lead to autocrine suppression of subsequent SC activity. Instead, PF bursts decrease the amplitude of disynaptic inhibition in PCs by evoking endocannabinoid release that transiently reduces the ability of PF synapses to trigger spikes in SCs. Thus, local interneurons within the cerebellum can release endocannabinoids through metabotropic glutamate receptor- and NMDAR-dependent mechanisms and contribute to use-dependent modulation of circuit properties.}, Author = {Beierlein, Michael and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Piperidines;Excitatory Amino Acid Antagonists;Calcium Chloride;Calcium Signaling;Animals;Synapses;Rats;Egtazic Acid;Synaptic Transmission;Excitatory Amino Acid Agonists;Patch-Clamp Techniques;Rats, Sprague-Dawley;Mice, Inbred C57BL;Endocannabinoids;Lipoprotein Lipase;Cerebellar Cortex;Action Potentials;Mice, Knockout;21 Neurophysiology;research support, n.i.h., extramural;Mice;Interneurons;24 Pubmed search results 2008;Pyrazoles;Receptors, Metabotropic Glutamate;Receptors, N-Methyl-D-Aspartate;Receptor, Cannabinoid, CB1;Excitatory Postsynaptic Potentials}, Month = {9}, Nlm_Id = {8102140}, Number = {39}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {9935-43}, Pii = {26/39/9935}, Pubmed = {17005857}, Title = {Local interneurons regulate synaptic strength by retrograde release of endocannabinoids}, Uuid = {26900215-F5BC-4C85-89BC-7B61343F92F6}, Volume = {26}, Year = {2006}, url = {papers/Beierlein_JNeurosci2006a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0958-06.2006}} @article{Beierlein:2006a, Abstract = {Changes in synaptic strength during ongoing activity are often mediated by neuromodulators. At the synapse between cerebellar granule cell parallel fibers (PFs) and Purkinje cells (PCs), brief bursts of stimuli can evoke endocannabinoid release from PCs and GABA release from interneurons that both inhibit transmission by activating presynaptic G-protein-coupled receptors. Studies in several brain regions suggest that synaptic activity can also evoke calcium signals in astrocytes, thereby causing them to release a transmitter, which acts presynaptically to regulate neurotransmitter release. In the cerebellum, Bergmann glia cells (BGs) are intimately associated with PF synapses. However, the mechanisms leading to calcium signals in BGs under physiological conditions and the role of BGs in regulating ongoing synaptic transmission are poorly understood. We found that brief bursts of PF activity evoke calcium signals in BGs that are triggered by the activation of metabotropic glutamate receptor 1 and purinergic receptors and mediated by calcium release from IP3-sensitive internal stores. We found no evidence for modulation of release from PFs mediated by BGs, even when endocannabinoid- and GABA-mediated presynaptic modulation was prominent. Thus, despite the fact that PF activation can reliably evoke calcium transients within BGs, it appears that BGs do not regulate synaptic transmission on the time scale of seconds to tens of seconds. Instead, endocannabinoid release from PCs and GABA release from molecular layer interneurons provide the primary means of feedback that dynamically regulate release from PF synapses.}, Author = {Beierlein, Michael and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Electric Stimulation;Nerve Fibers;Neuroglia;research support, n.i.h., extramural ;21 Neurophysiology;Presynaptic Terminals;Rats;in vitro ;Signal Transduction;Calcium;Cerebellum;Electrophysiology;Receptors, Metabotropic Glutamate;Animals;Receptors, Purinergic P2;24 Pubmed search results 2008;Neurons}, Month = {6}, Nlm_Id = {8102140}, Number = {26}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {6958-67}, Pii = {26/26/6958}, Pubmed = {16807325}, Title = {Brief bursts of parallel fiber activity trigger calcium signals in bergmann glia}, Uuid = {DDAC3052-7FAD-4806-BD99-7AF36C7A53B1}, Volume = {26}, Year = {2006}, url = {papers/Beierlein_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0613-06.2006}} @article{Belachew:2003, Abstract = {Neurogenesis is known to persist in the adult mammalian central nervous system (CNS). The identity of the cells that generate new neurons in the postnatal CNS has become a crucial but elusive issue. Using a transgenic mouse, we show that NG2 proteoglycan-positive progenitor cells that express the 2',3'-cyclic nucleotide 3'-phosphodiesterase gene display a multipotent phenotype in vitro and generate electrically excitable neurons, as well as astrocytes and oligodendrocytes. The fast kinetics and the high rate of multipotent fate of these NG2+ progenitors in vitro reflect an intrinsic property, rather than reprogramming. We demonstrate in the hippocampus in vivo that a sizeable fraction of postnatal NG2+ progenitor cells are proliferative precursors whose progeny appears to differentiate into GABAergic neurons capable of propagating action potentials and displaying functional synaptic inputs. These data show that at least a subpopulation of postnatal NG2-expressing cells are CNS multipotent precursors that may underlie adult hippocampal neurogenesis. 0021-9525 Journal Article}, Author = {Belachew, S. and Chittajallu, R. and Aguirre, A. A. and Yuan, X. and Kirby, M. and Anderson, S. and Gallo, V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {Spheroids, Cellular;gamma-Aminobutyric Acid/metabolism;Animals, Newborn;Mice;Mice, Transgenic;Support, U.S. Gov't, P.H.S.;Cells, Cultured;03 Adult neurogenesis progenitor source;Recombinant Fusion Proteins/diagnostic use;Promoter Regions (Genetics);2',3'-Cyclic-Nucleotide Phosphodiesterases/genetics/metabolism;Models, Animal;Action Potentials;Antigens/genetics/*metabolism;Cell Differentiation/*genetics;Action Potentials/genetics;Intermediate Filament Proteins;Proteoglycans;Multipotent Stem Cells/cytology/*metabolism;Antigens;Research Support, U.S. Gov't, P.H.S.;Recombinant Fusion Proteins;Phenotype;Hippocampus/cytology/*growth &development/*metabolism;gamma-Aminobutyric Acid;Multipotent Stem Cells;Neural Pathways/cytology/growth &development/metabolism;Neurons;Proteoglycans/genetics/*metabolism;Neural Pathways;Astrocytes/cytology/metabolism;02 Adult neurogenesis migration;Hippocampus;Astrocytes;Promoter Regions (Genetics)/genetics;Neurons/cytology/*metabolism;Dentate Gyrus;BB abstr;Animals;Research Support, Non-U.S. Gov't;Oligodendroglia;Cell Differentiation;Spheroids, Cellular/cytology/metabolism;Intermediate Filament Proteins/metabolism;2',3'-Cyclic-Nucleotide Phosphodiesterases;Dentate Gyrus/cytology/growth &development/metabolism;Oligodendroglia/cytology/metabolism;Support, Non-U.S. Gov't;Nerve Tissue Proteins}, Medline = {22581681}, Month = {4}, Nlm_Id = {0375356}, Number = {1}, Organization = {Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010-2970, USA.}, Pages = {169-86}, Pii = {jcb.200210110}, Pubmed = {12682089}, Title = {Postnatal NG2 proteoglycan-expressing progenitor cells are intrinsically multipotent and generate functional neurons}, Uuid = {E0CA380F-2C49-4328-BB6D-97EA1D852DCC}, Volume = {161}, Year = {2003}, url = {papers/Belachew_JCellBiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200210110}} @article{Belenkov:1969, Author = {Belenkov, N. Y. and Chirkov, V. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0013-4694}, Journal = {Electroencephalogr Clin Neurophysiol}, Keywords = {Epilepsy;21 Epilepsy;Electric Conductivity;Electroencephalography;21 Neurophysiology;Cats;Neural Conduction;Silver;Animals;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Medline = {70035687}, Month = {9}, Nlm_Id = {0375035}, Number = {7}, Pages = {698-9}, Pubmed = {4187388}, Title = {The role of electrical conductivity in the spread of epileptiform activity in the cortex}, Uuid = {19C9075A-864A-4D9B-99DE-A3D0708690D1}, Volume = {27}, Year = {1969}} @article{Bellander:2004, Abstract = {The complement cascade has been suggested to be involved in development of secondary brain damage following traumatic brain injury (TBI). Previous studies have shown that reactive microglia are involved in activation of the complement cascade following various injuries to the nervous system. Macrophages seem to have a significant role in this process, but it is still unclear whether these cells, as well as the complement components, are derived from reactive microglia or if these biological events only can occur as a result from the influx of plasma and monocytes via a disrupted blood-brain barrier (BBB). The aim of this study was to investigate the response of microglial cells and the complement system in the absence of plasma/blood components following a standardized crush injury in an entorhinal-hippocampal slice culture. There was a clear increase in complement component C1q and C5b-9-IR (Membrane Attack Complex, MAC) in the area near the crush injury. MAC-IR appeared as numerous dots in clusters which co-localized with anti-NeuN labelled neurons in the injury border zone. Complement C1q-IR co-localized with reactive microglia, co-labelled with OX42 antisera. These findings show activation of the complement cascade near the injury zone and in particular, formation of MAC at the surface of neurons in this area. There was a distinct activation of microglial cells (OX42-IR) near the site of injury, as well as an increase in ED-1 expressing macrophages. In the absence of blood and plasma components it is likely that ED-1-labelled cells represent reactive microglia transformed into macrophages. In addition, Neurons (Neun-IR) near the injury were found to co-localize with clusterin-IR indicating upregulation of a defense system to the endogenous complement attack. The present study provides evidence that microglia and complement is activated in the injury border zone of the tissue slice in a similar fashion as in vivo following TBI, despite the absence of plasma/blood products and cells. These findings support the hypothesis that reactive microglia have a key role in complement activation following TBI by local synthesis of complement with a potential impact on development of secondary neuronal insults.}, Author = {Bellander, Bo-Michael M. and Bendel, Olof and Von Euler, Gabriel and Ohlsson, Marcus and Svensson, Mikael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0897-7151}, Journal = {J Neurotrauma}, Keywords = {Complement Activation;Male;Rats, Sprague-Dawley;Hippocampus;Immunohistochemistry;Female;Rats;11 Glia;Microglia;Organ Culture;Support, Non-U.S. Gov't;Entorhinal Cortex;Animals;Neurons;Brain Injuries}, Month = {5}, Nlm_Id = {8811626}, Number = {5}, Organization = {Department of Clinical Neuroscience, Section for Neurosurgery, Karolinska Hospital, Stockholm, Sweden. bob\@ks.se}, Pages = {605-15}, Pubmed = {15165368}, Title = {Activation of microglial cells and complement following traumatic injury in rat entorhinal-hippocampal slice cultures}, Uuid = {1336ED50-0F9E-4333-B78E-3A7BFA8CF66A}, Volume = {21}, Year = {2004}, url = {papers/Bellander_JNeurotrauma2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/089771504774129937}} @article{Belluscio:2002, Abstract = {The mammalian olfactory system detects and discriminates thousands of odorants using many different receptors expressed by sensory neurons in the nasal epithelium. Axonal projections from these neurons to the main olfactory bulbs form reproducible patterns of glomeruli in two widely separated regions of each bulb, creating two mirror-symmetric maps of odorant receptor projections. To investigate whether odorant receptors organize neural circuitry in the olfactory bulb, we have examined a genetically modified mouse line, rI7 -->M71, in which a functionally characterized receptor, rI7, has been substituted into the M71 receptor locus. Here we show that despite their ectopic location the resulting glomeruli are responsive to known ligands of the rI7 receptor, attract postsynaptic innervation by mitral/tufted cell dendrites, and endow these cells with responses that are characteristic of the rI7 receptor. External tufted cells receiving input from rI7 -->M71 glomeruli form precise intrabulbar projections that link medial and lateral rI7 -->M71 glomeruli anatomically, thus providing a substrate for coordinating isofunctional glomeruli. We conclude that odorant receptor identity in epithelial neurons determines not only glomerular convergence and function, but also functional circuitry in the olfactory bulb. 0028-0836 Journal Article}, Author = {Belluscio, L. and Lodovichi, C. and Feinstein, P. and Mombaerts, P. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:41 -0400}, Journal = {Nature}, Keywords = {Olfactory Pathways/*physiology;Neurons, Afferent/physiology;Ligands;Rats;Immunohistochemistry;Receptors, Odorant/genetics/*physiology;Epithelium/metabolism;I pdf;Mice, Transgenic;Support, U.S. Gov't, P.H.S.;Olfactory Bulb/*physiology;Electrophysiology;Support, Non-U.S. Gov't;Animals;13 Olfactory bulb anatomy;Mice}, Number = {6904}, Organization = {Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. belluscl\@ninds.nih.gov}, Pages = {296-300}, Title = {Odorant receptors instruct functional circuitry in the mouse olfactory bulb}, Uuid = {1585344D-C2C8-4798-B681-A1FFCCD650F2}, Volume = {419}, Year = {2002}, url = {papers/Belluscio_Nature2002.pdf}} @article{Belmonte:2004, Author = {Belmonte, Matthew K. and Allen, Greg and Beckel-Mitchener, Andrea and Boulanger, Lisa M. and Carper, Ruth A. and Webb, Sara J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Fragile X Syndrome;Synapses;10 Development;research support, non-u.s. gov't;Neuronal Plasticity;Neural Pathways;Cerebellum;Autistic Disorder;10 genetics malformation;Child;Humans;Brain;24 Pubmed search results 2008;review}, Month = {10}, Nlm_Id = {8102140}, Number = {42}, Organization = {Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge CB2 2AH, United Kingdom.}, Pages = {9228-31}, Pii = {24/42/9228}, Pubmed = {15496656}, Title = {Autism and abnormal development of brain connectivity}, Uuid = {57D644E1-78AC-415A-BD5F-61931A5389DF}, Volume = {24}, Year = {2004}, url = {papers/Belmonte_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3340-04.2004}} @article{Belvindrah:2002, Abstract = {mCD24, a glycosylphosphatidylinositol-anchored highly glycosylated molecule, is expressed on differentiating neurons during development. In the adult CNS, its expression is restricted to immature neurons located in two regions showing ongoing neurogenesis: the subventricular zone (SVZ) of the lateral ventricle pathway and the dentate gyrus (DG) of the hippocampal formation. Here, combining bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen labelings we confirmed that mCD24 is expressed on proliferating cells. To determine whether the inactivation of the molecule may affect adult neurogenesis, we analyzed the phenotype of mCD24-deficient mice (mCD24-/-). We labeled cells in S-phase with a pulse, a long, or a cumulative administration of BrdU and analyzed cells in different zones according to their dividing rate (rapid and slow) both in the control and mCD24-/-. We found a significant increase in the number of rapid (in the SVZ and the DG) and slow (in the SVZ) proliferating cells. Cumulative assays revealed a global reduction of the total cell cycle duration of rapidly proliferating precursors of SVZ. We investigated the fate of supernumerary cells and observed an increased number of apoptotic cells (terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling) in the mutant SVZ. Furthermore, we found no difference in the size of the olfactory bulb between wild-type (WT) and mutant mice. In support, mCD24 deletion did not appear to affect migration in the migratory stream. A comparison of the organization of migrating precursors between WT and mCD24 -/-, both in vivo at the optic and electron microscopic levels and in SVZ cultured explants, did not show any changes in the arrangement of neuroblasts in chain-like structures. Altogether, our data suggest that mCD24 regulates negatively cell proliferation in zones of secondary neurogenesis.}, Author = {Belvindrah, Richard and Rougon, Genevi\`{e}ve and Chazal, Genevi\`{e}ve}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Animals;Phenotype;Cell Cycle;Apoptosis;Proliferating Cell Nuclear Antigen;Antigens, CD;Cell Count;Cell Movement;Mice, Inbred C57BL;Antigens, CD24;Olfactory Bulb;Membrane Glycoproteins;Mice, Knockout;Neurons;Dentate Gyrus;In Situ Nick-End Labeling;Mice;Cell Division;24 Pubmed search results 2008;Stem Cells;Bromodeoxyuridine;Lateral Ventricles;Research Support, Non-U.S. Gov't}, Medline = {21975474}, Month = {5}, Nlm_Id = {8102140}, Number = {9}, Organization = {Neurogen\`{e}se et Morphogen\`{e}se dans le d{\'e}veloppement et chez l'adulte/Institut de Biologie du D{\'e}veloppement de Marseille, Centre National de la Recherche Scientifique, Universit{\'e} de la M{\'e}diterran{\'e}e, Campus de Luminy, 13288 Marseille, France.}, Pages = {3594-607}, Pii = {22/9/3594}, Pubmed = {11978835}, Title = {Increased neurogenesis in adult mCD24-deficient mice}, Uuid = {433DCD4D-F50A-40BE-AE1F-7ECB915A7BE8}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/20026367}} @article{Belvindrah:2007, Abstract = {The subventricular zone (SVZ) of the lateral ventricle is the major site of neurogenesis in the adult brain. Neuroblasts that are born in the SVZ migrate as chains along the rostral migratory stream (RMS) to the olfactory bulb. Little is known about the mechanisms that control interactions between neuroblasts during their migration. Here we show that migrating neuroblasts express beta1 integrins and that the integrin ligand laminin is localized to cell chains. Using genetically modified mice and time-lapse video recordings of SVZ explants, we demonstrate that beta1 integrins and laminin promote the formation of cell chains. Laminin also induces the aggregation of purified neuroblasts. We conclude that the formation of cell chains in the RMS is controlled in part by beta1 integrins via binding to laminin. In addition, we provide evidence that beta1 class integrins are required for the maintenance of the glial tubes and that defects in the glial tubes lead to the ectopic migration of neuroblasts into the surrounding tissue.}, Author = {Belvindrah, Richard and Hankel, Sabine and Walker, John and Patton, Bruce L. and M{\"u}ller, Ulrich}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {02 Adult neurogenesis migration;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8102140}, Number = {10}, Organization = {The Scripps Research Institute, Department of Cell Biology, Institute for Childhood and Neglected Disease, La Jolla, California 92037, USA.}, Pages = {2704-17}, Pii = {27/10/2704}, Pubmed = {17344408}, Title = {Beta1 integrins control the formation of cell chains in the adult rostral migratory stream}, Uuid = {53C5C213-983D-43BF-92E5-A877D8B00F84}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2991-06.2007}} @article{Ben-Ari:2005, Abstract = {PURPOSE OF REVIEW: The polarity of action of gamma-aminobutyric acid (GABA) changes from inhibition to excitation in the developing brain and in epilepsies. This review deals with recent observations concerning the mechanisms and clinical implications of the shift in GABA's activity from inhibition to excitation. RECENT FINDINGS: GABAergic synapses provide most transmitter-gated inhibition and are the targets of numerous clinically active agents, notably antiepileptic drugs. In a wide range of brain structures and species, GABAergic synapses are excitatory during maturation because of a higher concentration of intracellular chloride. These findings suggest that activation of GABA synapses will excite foetal neurones while inhibiting those of the mother. In epilepsies, recurrent seizures also lead to an accumulation of chloride and an excitatory action of GABA. These observations have major implications for clinical practice and research. They suggest that use of benzodiazepines by pregnant mothers may lead to deleterious consequences when they are taken during the period when GABA is the main excitatory transmitter. Because neuronal activity alters important cell functions, including migration and morphogenesis, aberrant excessive excitation may lead to profound deleterious consequences. SUMMARY: In several physiological and pathological conditions, activation of GABAergic synapses excites neurones instead of producing classical inhibition. This shift, which is due to an intracellular accumulation of chloride, has major consequences for both the operation of networks and the pathogenic effects of epilepsies. This is particularly important in the immature brain, where the excitatory actions of GABA are particularly prominent.}, Author = {Ben-Ari, Yehezkel and Holmes, Gregory L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {1350-7540}, Journal = {Curr Opin Neurol}, Keywords = {Epilepsy;21 Neurophysiology;gamma-Aminobutyric Acid;Humans;Brain Chemistry;24 Pubmed search results 2008;21 Epilepsy;review}, Month = {4}, Nlm_Id = {9319162}, Number = {2}, Organization = {Institut de Neurobiologie de le M{\'e}diterran{\'e}e, INSERM, Parc scientifique de Luminy, Marseilles, France. ben-ari\@inmed.univ-mrs.fr}, Pages = {141-5}, Pii = {00019052-200504000-00011}, Pubmed = {15791144}, Title = {The multiple facets of gamma-aminobutyric acid dysfunction in epilepsy}, Uuid = {9CBFC507-01E7-4295-89C1-9DD1974E5071}, Volume = {18}, Year = {2005}} @article{Ben-Ari:2001, Abstract = {The events that follow epilepsy seizures are not restricted to the immediate period. A series of long-term alterations occurs, including synaptic rearrangements, which have an impact on the brain circuit's mode of operation. With models of temporal lobe epilepsy, seizures have been shown to generate long-lasting changes in synaptic efficacy (epileptic long-term potentiation) because of removal of the magnesium block, activation of N-methyl-D-aspartate receptors, and an increase in intracellular calcium. This novel form of synaptic plasticity provides a link between memory effects and pathologic processes. Additionally, high-affinity kainate autoradiography, Timm stain, intraventricular injection of kainic acid, and 3D reconstruction experiments clearly indicate that even brief seizures produce changes in synaptic efficacy, followed 2-3 weeks later by aberrant neosynapse formation. Several key steps have been identified in the cascade leading from transient hyperactivity episodes to long-lasting, quasi-permanent modification of the neuronal circuit organization. These include the activation of immediate-early genes, activation of growth factor genes within hours, alterations in glutamate receptors, glial hypertrophy, and cytoskeletal protein changes. The cascade is activated by the increase in intracellular calcium and leads to axonal growth and neosynapse formation, which in turn participates in the etiology of the syndrome by reducing the threshold for further seizures. In summary, study data imply that the mature epileptic circuit has unique features in comparison with those present before a seizure episode, including new receptors, ionic channels, and other proteins. It is therefore essential to develop novel strategies based on the unique mode of operation of the mature epileptic circuit, rather than on acute models of epilepsy.}, Author = {Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {gamma-Aminobutyric Acid;Long-Term Potentiation;Animals;In Vitro;Humans;Rats;Neuronal Plasticity;Seizures;Synaptic Transmission;21 Epilepsy;review;Hippocampus;Kainic Acid;Status Epilepticus;Epilepsy, Temporal Lobe;21 Neurophysiology;24 Pubmed search results 2008;Cell Death}, Medline = {21411621}, Nlm_Id = {2983306R}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e (INMED), INSERM U29, Route de Luminy, 13273 Marseille, France. ben-ari\@inmed.univ-mrs.fr}, Pages = {5-7}, Pii = {epi01003}, Pubmed = {11520314}, Title = {Cell death and synaptic reorganizations produced by seizures}, Uuid = {F6C37A9C-9E66-4D5D-A82C-0BD157BF38E9}, Volume = {42 Suppl 3}, Year = {2001}} @article{Ben-Ari:2006, Abstract = {The construction of the human brain with its 10(15) synapses follows a set of complex developmentally and environmentally regulated steps. A series of sequences have been described that are instrumental, in the sense that a failure of any one of them leads to dramatic, life-long consequences. Hence the importance of determining the sequential maturation of neurons, synapses and cortical maps. It is also important to determine how network-driven events become installed, as neuronal activity intervenes in all of these steps and modulates, for better or worse, the outcome. A fundamental consequence of these sequential events is that any disruption will have very different consequences depending on when it occurs, indeed, "when is as important as what". An obvious aspect of these general features is related to seizures. In fact, the developing brain has both a higher incidence of seizures in human and animal models, and experiences seizures that can produce long-lasting consequences that are also stage-dependent.This seminar and the series of slides presented are an introduction to these issues, summing up several studies made notably by INMED researchers during the last two decades (http://www.inmednet.com). It concentrates on four basic developmental rules: i) the generation by very immature neurons, of very large currents mediated by the activation of receptors in neurons that bear no synapses. This is due to the release of GABA that diffuses to distal sites and acts as a paracrine factor; ii) the excitatory/inhibitory shift of the actions of GABA during development because of a progressive reduction in the intracellular chloride concentration; iii) the sequential formation of GABAergic synapses and networks before glutamatergic ones, implying that, at an early stage, all the excitatory drive will be GABAergic; iv) the presence, at an early stage, of a unique, primitive pattern in all developing structures, this pattern disappears when most GABAergic synapses have shifted to their adult configuration.Several consequences of these sequences are described including: i) a control of neuronal migration by GABA-acting drugs, and the possibility that migration disorders are also generated by environmental factors that include the effects of GABA-acting agents; ii) If GABA excites immature neurons and inhibits adult one, then GABA-acting agents will also produce different effects on the mother and the embryo; iii) early brain oscillations are generated by the periphery and propagate centrally - notably to the sensory-motor cortex, suggesting that peripherally-generated movements may provide an important signal for the formation of cortical maps, in keeping with the importance of embryonic movements; iv) "seizures beget seizures" in the developing brain. This has now been shown in a triple chamber with the two intact hippocampi that we developed, and with which it has been possible to show that only recurrent seizures that include high frequency oscillations can transform the na{\"\i}ve, contralateral hippocampus to an epileptic one that seizes spontaneously. Most interestingly, at an early developmental stage, when GABA excites many neurons and the density of glutamatergic synapses is not sufficiently high, purely glutamatergic seizures cannot lead to long-term consequences, the additional excitatory drive provided by GABAergic synapses is needed. In other words, at that stage, blocking GABA synapses generates seizures, as in adults, but these do not lead to long-term consequences. The mechanisms that underlie these differences is due to the need for high frequency oscillations (> 80 Hz or so), and these can only be generated when GABA synapses are operative in the developing brain: GABA receptor antagonists are ictogenic, but not epileptogenic.To facilitate teaching purposes the paper is published together with supplemental data (as a PowerPoint presentation included in the accompanying DVD), thus allowing an overview of important developmental steps and their implications.}, Author = {Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {1294-9361}, Journal = {Epileptic Disord}, Keywords = {Epilepsy;Brain;Synapses;Glutamic Acid;24 Pubmed search results 2008;21 Neurophysiology;Paracrine Communication;21 Epilepsy;Neurotransmitter Agents;gamma-Aminobutyric Acid;Animals;Humans;Cell Movement;Neurons;review}, Month = {6}, Nlm_Id = {100891853}, Number = {2}, Organization = {INMED/INSERM, Parc Scientifique de Luminy, Marseille, France. ben-ari\@inmed.univ-mrs.fr}, Pages = {91-102}, Pubmed = {16793570}, Title = {Basic developmental rules and their implications for epilepsy in the immature brain}, Uuid = {9500E0E2-F928-44B4-BB63-9FEC89DECFCE}, Volume = {8}, Year = {2006}} @article{Ben-Ari:1989, Abstract = {1. Intracellular recordings were made from rat CA3 hippocampal neurones in vitro during the first eighteen days of postnatal life. The cells had resting membrane potentials more negative than -51 mV, action potentials greater than 55 mV and membrane input resistances of 117 +/- 12 M omega. An unusual characteristic of these cells was the presence of spontaneous giant depolarizing potentials (GDPs) which were observed during the first eight postnatal (P) days in over 85\%of neurones. They were less frequent between P9 and P12 (48\%) and disappeared after P12. 2. The GDPs were synchronously generated by a population of neurones; they reversed polarity at -27 mV when recorded with KCl-containing electrodes and at -51 mV with potassium acetate- or potassium methylsulphate-filled electrodes. 3. The GDPs were blocked by bath application of bicuculline (10 microM) or picrotoxin (100-200 microM). Exogenously applied gamma-aminobutyric acid (GABA; 0.2-1 mM) induced at resting membrane potential a bicuculline-sensitive membrane depolarization which reversed polarity at -25 and -51 mV when recorded with KCl- or potassium methylsulphate-filled electrodes respectively. 4. The GDPs were reduced in frequency or blocked by the N-methyl-D-aspartate (NMDA) receptor antagonists DL-2-amino-7-phosphonoheptanoate (AP-7; 50 microM), D(-)2-amino-5-phosphonovalerate (AP-5, 10-50 microM) and (+-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP, 10-50 microM) or NMDA channel blockers phencyclidine (2 microM) and ketamine (20 microM). 5. Stimulation of the hilus during the first week of life evoked a GDP followed by a hyperpolarization. The GDPs were generated by a population of synchronized neurones and reversed polarity at -27 mV with KCl-filled electrodes and at -52 mV with potassium acetate- or potassium methylsulphate-containing electrodes. 6. Bath application of bicuculline (1-10 microM) or picrotoxin (100-200 microM) reversibly blocked the evoked GDPs in the majority of cells. The NMDA receptor antagonists AP-5 (50 microM), AP-7 (50 microM) and CPP (30 microM) usually reduced the amplitude and the duration of the evoked GDPs. In neurones in which evoked GDPs were blocked by bicuculline, a NMDA-mediated component was revealed by increasing the strength or the frequency of stimulation. 7. During the second week of postnatal life, when spontaneous GDPs were extremely rare or absent, superfusion with bicuculline (10 microM) induced, as in adult slices, interictal discharges. These reversed polarity near 0 mV with KCl- or potassium acetate-containing electrodes and were reduced in amplitude and duration by AP-5 (50 microM).(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Ben-Ari, Y. and Cherubini, E. and Corradetti, R. and Gaiarsa, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {gamma-Aminobutyric Acid;Animals;Evoked Potentials;Rats;21 Epilepsy;Ketamine;2-Amino-5-phosphonovalerate;Amino Acids;Hippocampus;Piperazines;Rats, Inbred Strains;Phencyclidine;Bicuculline;Animals, Newborn;Action Potentials;21 Neurophysiology;Picrotoxin;Membrane Potentials;Receptors, Neurotransmitter;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Research Support, Non-U.S. Gov't}, Medline = {90112082}, Month = {9}, Nlm_Id = {0266262}, Organization = {Unit{\'e} 29, INSERM, H\^{o}pital de Port-Royal, Paris, France.}, Pages = {303-25}, Pubmed = {2575165}, Title = {Giant synaptic potentials in immature rat CA3 hippocampal neurones}, Uuid = {FBEC0E7C-D067-11DA-8A8C-000D9346EC2A}, Volume = {416}, Year = {1989}, url = {papers/Ben-Ari_JPhysiol1989.pdf}} @article{Ben-Ari:2006a, Abstract = {Infants and children are at a high risk for seizures compared with adults. Although most seizures in children are benign and result in no long-term consequences, increasing experimental animal data strongly suggest that frequent or prolonged seizures in the developing brain result in long-lasting sequelae. Such seizures may intervene with developmental programmes and lead to inadequate construction of cortical networks rather than induction of neuronal cell loss. As a consequence, the deleterious actions of seizures are strongly age dependent: seizures have different effects on immature or migrating neurons endowed with few synapses and more developed neurons that express hundreds of functional synapses. This differential effect is even more important in human beings and subhuman primates who have an extended brain development period. Seizures also beget seizures during maturation and result in a replay of development programmes, which suggests that epileptogenesis recapitulates ontogenesis. Therefore, to understand seizures and their consequences in the developing brain, it is essential to determine how neuronal activity modulates the main steps of cortical formation. In this Review, we present basic developmental principles obtained from animal studies and examine the long-lasting consequences of epilepsy.}, Author = {Ben-Ari, Yehezkel and Holmes, Gregory L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1474-4422}, Journal = {Lancet Neurol}, Keywords = {24 Pubmed search results 2008;research support, non-u.s. gov't;21 Neurophysiology;Seizures;research support, n.i.h., extramural;Nerve Net;Humans;Animals;Brain;review;21 Epilepsy}, Month = {12}, Nlm_Id = {101139309}, Number = {12}, Organization = {Institute of Neurobiology of the Mediterranean Sea (INMED, INSERM and Universit{\'e} de la M{\'e}diterran{\'e}e), Marseilles, France. ben-ari\@inmed.univ-mrs.fr}, Pages = {1055-63}, Pii = {S1474-4422(06)70626-3}, Pubmed = {17110286}, Title = {Effects of seizures on developmental processes in the immature brain}, Uuid = {ACD97E03-CC9B-48D7-9E7D-9736AD916B6A}, Volume = {5}, Year = {2006}, url = {papers/Ben-Ari_LancetNeurol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S1474-4422(06)70626-3}} @article{Ben-Ari:2002, Abstract = {In the immature brain, GABA (gamma-aminobutyric acid) is excitatory, and GABA-releasing synapses are formed before glutamatergic contacts in a wide range of species and structures. GABA becomes inhibitory by the delayed expression of a chloride exporter, leading to a negative shift in the reversal potential for choride ions. I propose that this mechanism provides a solution to the problem of how to excite developing neurons to promote growth and synapse formation while avoiding the potentially toxic effects of a mismatch between GABA-mediated inhibition and glutamatergic excitation. As key elements of this cascade are activity dependent, the formation of inhibition adds an element of nurture to the construction of cortical networks.}, Author = {Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Animals;24 Pubmed search results 2008;Cell Differentiation;Research Support, Non-U.S. Gov't;Excitatory Postsynaptic Potentials;21 Neurophysiology;21 Epilepsy;Hippocampus;Chloride Channels;Receptors, GABA;gamma-Aminobutyric Acid;Synaptic Transmission;Nerve Net;Humans;Glutamic Acid;review;Receptors, Glutamate}, Medline = {22199621}, Month = {9}, Nlm_Id = {100962781}, Number = {9}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e (INMED), INSERM Unit 29, Parc Scientifique de Luminy, 13273 Marseille Cedex 09, France. ben-ari\@inmed.univ-mrs.fr}, Pages = {728-39}, Pii = {nrn920}, Pubmed = {12209121}, Title = {Excitatory actions of gaba during development: the nature of the nurture}, Uuid = {FBEBE2E4-D067-11DA-8A8C-000D9346EC2A}, Volume = {3}, Year = {2002}, url = {papers/Ben-Ari_NatRevNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn920}} @article{Ben-Ari:2000, Abstract = {Studies using kainate, an excitatory amino acid extracted from a seaweed, have provided major contributions to the understanding of epileptogenesis. Here we review pioneering and more recent studies aimed at determining how kainate generates seizures and, in particular, how inhibition is altered during seizures. We focus on target and subunit-specific effects of kainate on hippocampal pyramidal neurons and interneurons that lead to an excitation of both types of neurons and thus to the parallel increase of glutamatergic and GABAergic spontaneous currents. We propose that kainate excites all its targets, the net consequence depending on the level of activity of the network.}, Author = {Ben-Ari, Y. and Cossart, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Trends Neurosci}, Keywords = {Seizures/*chemically induced/physiopathology;E-15;Presynaptic Terminals/metabolism;Electric Conductivity;07 Excitotoxicity Apoptosis;GABA/metabolism;Epilepsy, Temporal Lobe/chemically induced;*Kainic Acid/pharmacology;Pyramidal Cells/metabolism;Synapses/physiology;Neural Inhibition;Animal;Receptors, Kainic Acid;*Excitatory Amino Acid Agonists/pharmacology;Disease Models, Animal;Glutamic Acid/metabolism}, Number = {11}, Organization = {The INMED, INSERM U29, Parc scientifique de Luminy, BP 13, 13273, Marseille, France.}, Pages = {580-7.}, Title = {Kainate, a double agent that generates seizures: two decades of progress}, Uuid = {D0D76618-98AE-4185-98CF-829FDC00B23A}, Volume = {23}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11074268}} @article{Ben-Ari:2001a, Abstract = {During development, when synapses start to be established, a primitive form of network-driven activity provides most of the synaptic activity. This pattern enables a high degree of synchrony in immature neurons in spite of the small number of functional synapses and could participate in activity-dependent growth and synapse formation. Relying on the giant depolarizing potentials that provide most of the synaptic activity in the developing hippocampus, this article reviews the common properties and generating mechanisms of these patterns, and particularly the role of the early depolarizing action of GABA(A) and glycine receptors and the sequential expression of GABA and glutamate synapses. Patterns similar to giant depolarizing potentials have been observed in a wide range of structures and species suggesting that there is a temporal template throughout evolution that constitutes an essential step in the formation of functional networks.}, Author = {Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:42:35 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Synapses;24 Pubmed search results 2008;21 Epilepsy;21 Neurophysiology;Action Potentials;Receptors, GABA;Nerve Net;Humans;Animals;Brain;review;Excitatory Amino Acid Antagonists}, Medline = {21256346}, Month = {6}, Nlm_Id = {7808616}, Number = {6}, Organization = {INMED, INSERM U29, Avenue de Luminy, B.P. 13, 13273 Cedex 09, Marseille, France. ben-ari\@inmed.univ-mrs.fr}, Pages = {353-60}, Pii = {S0166-2236(00)01813-0}, Pubmed = {11356508}, Title = {Developing networks play a similar melody}, Uuid = {883B30E6-9B1C-46FF-A65E-7183F8B55331}, Volume = {24}, Year = {2001}, url = {papers/Ben-Ari_TrendsNeurosci2001.pdf}} @article{Ben-Ari:2004, Author = {Ben-Ari, Yehezkel and Spitzer, Nicholas C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:40 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Neurobiology;21 Epilepsy;21 Neurophysiology;congresses;Animals;editorial;Brain;Humans;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7808616}, Number = {7}, Pages = {361}, Pii = {S0166223604001614}, Pubmed = {15219731}, Title = {Nature and nurture in brain development}, Uuid = {AF5B4AF7-D7E1-4F90-9379-7FEA482E8C76}, Volume = {27}, Year = {2004}, url = {papers/Ben-Ari_TrendsNeurosci2004.pdf}, Bdsk-File-2 = {papers/Ben-Ari_TrendsNeurosci2004a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2004.05.007}} @article{Ben-Ari:2004a, Abstract = {Despite a rather long migratory journey, interneurons are functional before vertically migrating pyramidal neurons and they constitute the source and target of the first functional synapses in the developing hippocampus. Interneuron-driven network patterns are already present in utero while principal cells are mostly quiescent. At that early stage, GABAergic synapses--which are formed before glutamatergic ones--are excitatory, suggesting that GABA is a pioneer, much like the neurons from which it is released. This review discusses this sequence of events, its functional significance and the role that interneurons might play in the construction of cortical networks.}, Author = {Ben-Ari, Yehezkel and Khalilov, Ilgam and Represa, Alfonso and Gozlan, Henri}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {21 Epilepsy;21 Neurophysiology;Cell Communication;Pyramidal Cells;Neural Pathways;Interneurons;Animals;Cell Movement;Cerebral Cortex;review;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7808616}, Number = {7}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e (INMED), Parc Scientifique de Luminy, BP13, 13009 Marseille, France. ben-ari\@inmed.univ-mrs.fr}, Pages = {422-7}, Pii = {S0166223604001559}, Pubmed = {15219742}, Title = {Interneurons set the tune of developing networks}, Uuid = {87228E2B-0847-482D-82B3-D22CF1BD032F}, Volume = {27}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2004.05.002}} @article{Ben-Ari:2006b, Author = {Ben-Ari, Yehezkel and Represa, Alfonso}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {21 Neurophysiology;editorial;24 Pubmed search results 2008;21 Epilepsy}, Month = {7}, Nlm_Id = {7808616}, Number = {7}, Organization = {INMED-INSERM U29, 163 Route de Luminy, 13273 Marseille Cedex 09, France.}, Pages = {347-8}, Pii = {S0166-2236(06)00119-6}, Pubmed = {16806509}, Title = {Fourth INMED/TINS conference: Nature and nurture in brain development and neurological disorders}, Uuid = {B0E445E1-9B9E-4D41-92BA-AB83DF728BC6}, Volume = {29}, Year = {2006}, url = {papers/Ben-Ari_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.06.005}} @article{Ben-Hur:1998, Abstract = {Oligodendrocyte-type 2 astrocyte (O-2A) lineage cells are derived from multipotential stem cells of the developing CNS. Precursors of O-2A progenitors express the polysialylated (PSA) form of the neural cell adhesion molecule (NCAM) and are detected in neonatal rat brain glial cultures. It is unclear how such PSA-NCAM+ "pre-progenitors" are related to neural stem cells and whether they still have the potential to differentiate along several neural lineages. Here we isolated PSA-NCAM+ pre-progenitor cells from glial cultures by immunopanning and found that most of these cells expressed nestin and PDGF-receptor-alpha but not O-2A antigens. PSA-NCAM+ cells synthesized transcripts for fibroblast growth factor (FGF) receptors 1, 2, and 3 and responded to FGF2 by survival and proliferation, growing into large clusters resembling neural spheres. FGF2-induced proliferation of PSA-NCAM+ pre-progenitors was significantly enhanced by thyroid hormone (T3), which on its own did not increase cell survival or mitosis. After adhesion and withdrawal of the mitogen, spheres generated mostly oligodendrocytes and astrocytes but very rarely neurons. PSA-NCAM immunopanned cells grown in epidermal growth factor (EGF) also adopted a mostly glial fate after differentiation. In contrast, PSA-NCAM-negative cells and striatal neonatal stem cells, grown in EGF or FGF2, generated the three CNS cell types. Like neural stem cells, PSA-negative cells generated more oligodendrocytes and fewer neurons when expanded in FGF2 and T3. Thus emergence of PSA-NCAM at the surface of neonatal brain precursors coincides with their restriction to a glial fate. T3 modulates these events by enhancing PSA-NCAM+ pre-progenitor growth in FGF2 and favoring an oligodendrocyte fate.}, Author = {Ben-Hur, T. and Rogister, B. and Murray, K. and Rougon, G. and Dubois-Dalcq, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Astrocytes;Rats;Protein Precursors;Oligodendroglia;Rats, Sprague-Dawley;Fibroblast Growth Factor 2;03 Adult neurogenesis progenitor source;Receptors, Thyroid Hormone;Antigens;Animals, Newborn;Sialic Acids;Cell Lineage;Neural Cell Adhesion Molecule L1;Cell Division;Stem Cells;Nerve Tissue Proteins;Triiodothyronine;Neural Cell Adhesion Molecules}, Medline = {98337877}, Month = {8}, Nlm_Id = {8102140}, Number = {15}, Organization = {Unite de Neurovirologie et R{\'e}g{\'e}n{\'e}ration du Syst\`{e}me Nerveux, Institut Pasteur, 75724 Paris, France.}, Pages = {5777-88}, Pubmed = {9671666}, Title = {Growth and fate of PSA-NCAM+ precursors of the postnatal brain}, Uuid = {0759F17A-CC26-4A91-B288-41DBEE00EE38}, Volume = {18}, Year = {1998}, url = {papers/Ben-Hur_JNeurosci1998.pdf}} @article{Benardete:2002, Abstract = {PURPOSE: Cortical dysplasia (CD) is associated with epilepsy in both the pediatric and adult populations. The mechanism underlying seizures with cortical malformations is still poorly understood. To study the physiology of dysplastic cortex, we developed an experimental model of CD. METHODS: Pregnant rats were given intraperitoneal injections of carmustine (1-3-bis-chloroethyl-nitrosourea; BCNU) on embryonic day 15 (E15). Cortical histology was examined in the resulting pups at P0, P28, and P60. In addition, evoked and spontaneous field potential recordings were obtained in cortical slices from adult control and BCNU-exposed rats. Finally, we used whole-cell recordings to compare physiologic properties of pyramidal neurons and gamma-aminobutyric acid (GABA) responses in control and BCNU-treated animals. RESULTS: Features characteristic of CD were found in the offspring, including laminar disorganization, cytomegalic neurons, and neuronal heterotopias. Dysplastic cortex also contained abnormal clusters of Cajal-Retzius (CR) cells and disruption of radial glial fibers, as demonstrated with immunohistochemistry. Under conditions of partial GABAA-receptor blockade with 10 microM bicuculline methiodide (BMI), slices of dysplastic cortex demonstrated a significant increase in the number of spontaneous and evoked epileptiform discharges. Individual pyramidal neurons in dysplastic cortex were less sensitive to application of GABA compared with controls. CONCLUSIONS: BCNU exposure in utero produces histologic alterations suggestive of CD in rat offspring. Dysplastic cortex from this model demonstrates features of hyperexcitability and decreased neuronal sensitivity to GABA. Such physiologic alterations may underlie the increased epileptogenicity of dysplastic cortex.}, Author = {Benardete, Ethan A. and Kriegstein, Arnold R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {gamma-Aminobutyric Acid;Pregnancy;Electric Stimulation;Electrophysiology;Evoked Potentials;Animals;Rats;21 Epilepsy;Patch-Clamp Techniques;Female;Epilepsy;Pyramidal Cells;Carmustine;Disease Models, Animal;Bicuculline;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;Receptors, GABA;Litter Size;24 Pubmed search results 2008;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {22188635}, Month = {9}, Nlm_Id = {2983306R}, Number = {9}, Organization = {Department of Neurology and Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons; and Department of Neurosurgery, NYU Medical Center, New York, New York 10032, USA.}, Pages = {970-82}, Pii = {epi40901}, Pubmed = {12199722}, Title = {Increased excitability and decreased sensitivity to GABA in an animal model of dysplastic cortex}, Uuid = {8EF2545D-F1D8-4208-8E21-DB89DA262356}, Volume = {43}, Year = {2002}} @article{Benavides-Piccione:2006, Abstract = {Neocortical circuits share anatomical and physiological similarities among different species and cortical areas. Because of this, a 'canonical' cortical microcircuit could form the functional unit of the neocortex and perform the same basic computation on different types of inputs. However, variations in pyramidal cell structure between different primate cortical areas exist, indicating that different cortical areas could be built out of different neuronal cell types. In the present study, we have investigated the dendritic architecture of 90 layer II/III pyramidal neurons located in different cortical regions along a rostrocaudal axis in the mouse neocortex, using, for the first time, a blind multidimensional analysis of over 150 morphological variables, rather than evaluating along single morphological parameters. These cortical regions included the secondary motor cortex (M2), the secondary somatosensory cortex (S2), and the lateral secondary visual cortex and association temporal cortex (V2L/TeA). Confirming earlier primate studies, we find that basal dendritic morphologies are characteristically different between different cortical regions. In addition, we demonstrate that these differences are not related to the physical location of the neuron and cannot be easily explained assuming rostrocaudal gradients within the cortex. Our data suggest that each cortical region is built with specific neuronal components.}, Author = {Benavides-Piccione, Ruth and Hamzei-Sichani, Farid and Ballesteros-Y{\'a}\~{n}ez, Inmaculada and Defelipe, Javier and Yuste, Rafael ?}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {21 Neurophysiology;21 Calcium imaging;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {9110718}, Number = {7}, Organization = {Instituto Cajal, Madrid, Spain and.}, Pages = {990-1001}, Pii = {bhj041}, Pubmed = {16195469}, Title = {Dendritic Size of Pyramidal Neurons Differs among Mouse Cortical Regions}, Uuid = {70CD2730-4693-4625-9B83-CB74A716E096}, Volume = {16}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhj041}} @article{Bender:2003, Abstract = {The excitatory feedforward projection from layer (L) 4 to L2/3 in rat primary somatosensory (S1) cortex exhibits precise, columnar topography that is critical for columnar processing of whisker inputs. Here, we characterize the development of axonal topography in this projection using single-cell reconstructions in S1 slices. In the mature projection [postnatal day (P) 14-26], axons of L4 cells extending into L2/3 were confined almost entirely to the home barrel column, consistent with previous results. At younger ages (P8-11), however, axonal topography was significantly less columnar, with a large proportion of branches innervating neighboring barrel columns representing adjacent whisker rows. Mature topography developed from this initial state by targeted axonal growth within the home column and by growth of barrel columns themselves. Raising rats with all or a subset of whiskers plucked from P8-9, manipulations that induce reorganization of functional whisker maps and synaptic depression at L4 to L2/3 synapses, did not alter normal anatomical development of L4 to L2/3 axons. Thus, development of this projection does not require normal sensory experience after P8, and deprivation-induced reorganization of whisker maps at this age is unlikely to involve physical remodeling of L4 to L2/3 axons.}, Author = {Bender, Kevin J. and Rangel, Juliana and Feldman, Daniel E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;Electric Stimulation;Rats, Long-Evans;Lysine;In Vitro;Rats;Neuronal Plasticity;10 Structural plasticity;Animals;Beta;Patch-Clamp Techniques;Sensory Deprivation;Axons;Vibrissae;Dendrites;Support, Non-U.S. Gov't;10 Spiny stellate;Action Potentials;Neurons;Membrane Potentials;Somatosensory Cortex;Support, U.S. Gov't, P.H.S.;Age Factors;Brain Mapping}, Medline = {22871219}, Month = {9}, Nlm_Id = {8102140}, Number = {25}, Organization = {Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0357, USA.}, Pages = {8759-70}, Pii = {23/25/8759}, Pubmed = {14507976}, Title = {Development of columnar topography in the excitatory layer 4 to layer 2/3 projection in rat barrel cortex}, Uuid = {35AB084E-9D3F-42C8-B54F-4A00F9EAF1B9}, Volume = {23}, Year = {2003}, url = {papers/Bender_JNeurosci2003.pdf}} @article{Bengzon:1997, Abstract = {Neuronal apoptosis was observed in the rat dentate gyrus in two experimental models of human limbic epilepsy. Five hours after one hippocampal kindling stimulation, a marked increase of in situ terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) of fragmented DNA was observed in nuclei located within and on the hilar border of the granule cell layer and in the polymorphic region. Forty kindling stimulations with 5-min interval produced higher numbers of labeled nuclei compared with one stimulation. The increase of TUNEL-positive nuclei was prevented by the protein synthesis inhibitor cycloheximide but not affected by the N-methyl-D-aspartate receptor antagonist MK-801. Kainic acid-induced seizures lead to a pattern of labeling in the hippocampal formation identical to that evoked by kindling. A large proportion of cells displaying TUNEL-positive nuclei was double-labeled by the neuron-specific antigen NeuN, demonstrating the neuronal identity of apoptotic cells. Either 1 or 40 kindling stimulations also gave rise to a marked increase of the number of cells double-labeled with the mitotic marker bromodeoxyuridine and NeuN in the subgranular zone and on the hilar border of the dentate granule cell layer. The present data show that single and intermittent, brief seizures induce both apoptotic death and proliferation of dentate gyrus neurons. We hypothesize that these processes, occurring early during epileptogenesis, are primary events in the development of hippocampal pathology in animals and possibly also in patients suffering from temporal lobe epilepsy. 0027-8424 Journal Article}, Author = {Bengzon, J. and Kokaia, Z. and Elmer, E. and Nanobashvili, A. and Kokaia, M. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Rats, Sprague-Dawley;D abstr;Rats;Apoptosis;Cell Division;Limbic System/*pathology/physiopathology;06 Adult neurogenesis injury induced;Dentate Gyrus/*pathology/physiopathology;Support, Non-U.S. Gov't;Animals;Neurons/*pathology;Male;Epilepsy/*pathology/physiopathology}, Number = {19}, Organization = {Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, S-221 85 Lund, Sweden. johan.begzon\@neurol.lu.se}, Pages = {10432-7}, Pubmed = {9294228}, Title = {Apoptosis and proliferation of dentate gyrus neurons after single and intermittent limbic seizures}, Uuid = {67C412E5-EC82-11DA-8605-000D9346EC2A}, Volume = {94}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9294228}} @article{Bennett:2003, Abstract = {Neurofibromatosis type 1 (NF1) patients are predisposed to learning disabilities, macrocephaly, and brain tumors as well as abnormalities on magnetic resonance imaging that are postulated to result from abnormal myelination. Here we show that Nf1+/- spinal cords in adult mice have more than twofold-increased numbers of NG2+ progenitor cells. Nf1-/- embryonic spinal cords have increased numbers of Olig2+ progenitors. Also, cultures from Nf1 mutant embryos with hemizygous and biallelic Nf1 mutations have dramatically increased numbers of CNS oligodendrocyte progenitor cells. In medium that allows growth of neuroepithelial cells and glial progenitors, mutant cells hyper-respond to FGF2, have increased basal and FGF-stimulated Ras-GTP, and fail to accumulate when treated with a farnesyltransferase inhibitor. Cell accumulation results in part from increased proliferation and decreased cell death. In contrast to wild-type cells, Nf1-/- progenitors express the glial differentiation marker O4 while retaining expression of the progenitor marker nestin. Nf1 mutant progenitors also abnormally coexpress the glial differentiation markers O4 and GFAP. Importantly, Nf1-/- spinal cord-derived oligodendrocyte progenitors, which are amplified 12-fold, retain the ability to form oligodendrocytes after in vivo transplantation. The data reveal a key role for neurofibromin and Ras signaling in the maintenance of CNS progenitor cell pools and also suggest a potential role for progenitor cell defects in the CNS abnormalities of NF1 patients. 1529-2401 Journal Article}, Author = {Bennett, M. R. and Rizvi, T. A. and Karyala, S. and McKinnon, R. D. and Ratner, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Heterozygote;Spinal Cord/*pathology;Animals;Cells, Cultured;Stem Cell Transplantation;Neurons/pathology;ras Proteins/metabolism;Neurofibromin 1/*genetics;Female;Cell Count;Neurofibromatosis 1/genetics/*pathology;Mutation;Enzyme Inhibitors/pharmacology;11 Glia;Oligodendroglia/*pathology;Male;Mice, Neurologic Mutants;Mice, Inbred C57BL;Support, Non-U.S. Gov't;Cell Division/genetics;Mice, Knockout;Homozygote;Fibroblast Growth Factor 2/pharmacology;Stem Cells/drug effects/metabolism/*pathology;Support, U.S. Gov't, P.H.S.;Support, U.S. Gov't, Non-P.H.S.;Antigens, Differentiation/biosynthesis;Mice;G pdf}, Number = {18}, Organization = {Department of Cell Biology, Neurobiology, and Anatomy, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0521, USA.}, Pages = {7207-17}, Pubmed = {12904481}, Title = {Aberrant growth and differentiation of oligodendrocyte progenitors in neurofibromatosis type 1 mutants}, Uuid = {243C5C92-2D88-4B09-A7FD-DA2BCA87DD7D}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12904481}} @article{Benraiss:2001, Abstract = {Neural progenitor cells persist throughout the adult forebrain subependyma, and neurons generated from them respond to brain-derived neurotrophic factor (BDNF) with enhanced maturation and survival. To induce neurogenesis from endogenous progenitors, we overexpressed BDNF in the adult ventricular zone by transducing the forebrain ependyma to constitutively express BDNF. We constructed a bicistronic adenovirus bearing BDNF under cytomegalovirus (CMV) control, and humanized green fluorescent protein (hGFP) under internal ribosomal entry site (IRES) control. This AdCMV:BDNF:IRES:hGFP (AdBDNF) was injected into the lateral ventricles of adult rats, who were treated for 18 d thereafter with the mitotic marker bromodeoxyuridine (BrdU). Three weeks after injection, BDNF averaged 1 &mgr;g/gm in the CSF of AdBDNF-injected animals but was undetectable in control CSF. In situ hybridization demonstrated BDNF and GFP mRNA expression restricted to the ventricular wall. In AdBDNF-injected rats, the olfactory bulb exhibited a >2.4-fold increase in the number of BrdU(+)-betaIII-tubulin(+) neurons, confirmed by confocal imaging, relative to AdNull (AdCMV:hGFP) controls. Importantly, AdBDNF-associated neuronal recruitment to the neostriatum was also noted, with the treatment-induced addition of BrdU(+)-NeuN(+)- betaIII-tubulin(+) neurons to the caudate putamen. Many of these cells also expressed glutamic acid decarboxylase, cabindin-D28, and DARPP-32 (dopamine and cAMP-regulated phosphoprotein of 32 kDa), markers of medium spiny neurons of the neostriatum. These newly generated neurons survived at least 5-8 weeks after viral induction. Thus, a single injection of adenoviral BDNF substantially augmented the recruitment of new neurons into both neurogenic and non-neurogenic sites in the adult rat brain. The intraventricular delivery of, and ependymal infection by, viral vectors encoding neurotrophic agents may be a feasible strategy for inducing neurogenesis from resident progenitor cells in the adult brain.}, Author = {Benraiss, A. and Chmielnicki, E. and Lerner, K. and Roh, D. and Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {J Neurosci}, Keywords = {C both;04 Adult neurogenesis factors}, Number = {17}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021.}, Pages = {6718-31.}, Title = {Adenoviral brain-derived neurotrophic factor induces both neostriatal and olfactory neuronal recruitment from endogenous progenitor cells in the adult forebrain}, Uuid = {ED3188D6-8364-49A6-B474-5BE1935AF1A1}, Volume = {21}, Year = {2001}, url = {papers/Benraiss_JNeurosci2001.pdf}} @article{Berbel:1993, Abstract = {Callosal connections were studied with tracers (horseradish peroxidase (HRP) and wheat germ agglutinin-horseradish peroxidase (WGA-HRP)) in normal rats and rats deprived of thyroid hormones with methimazole (Sigma) since embryonic day 14 and thyroidectomized at postnatal day 6. In hypothyroid rats, the auditory areas, in particular the primary auditory area, showed cytoarchitectonic changes including blurred lamination and decrease in the size of layer V pyramidal neurons. In control rats, callosally-projecting neurons were found between layers II and VI with a peak in layer III and upper layer IV. In hypothyroid rats, labelled neurons were found between layers IV and VI with two peaks corresponding to layer IV and upper layer V, and in upper layer VI. Quantitative analysis of radial distribution of callosally-projecting neurons confirmed their shift to infragranular layers in hypothyroid rats. Three-dimensional reconstructions showed a more continuous tangential distribution of callosally-projecting neurons in hypothyroid rats which may be due to the maintenance of a juvenile 'exuberant' pattern of projections. These changes in cortical connectivity may be relevant for understanding epilepsy and mental retardation associated with early hypothyroidism in humans and to clarify basic mechanisms of cortical development.}, Author = {Berbel, P. and Guada\~{n}o-Ferraz, A. and Mart{\'\i}nez, M. and Quiles, J. A. and Balboa, R. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Wheat Germ Agglutinins;Hypothyroidism;Axonal Transport;Female;Methimazole;Rats;Not relevant;Rats, Wistar;11 Glia;Thyroidectomy;Auditory Pathways;Support, Non-U.S. Gov't;Horseradish Peroxidase;Animals;Neurons;Corpus Callosum}, Medline = {94115576}, Month = {11}, Nlm_Id = {8918110}, Number = {11}, Organization = {Departament d'Histologia, Facultat de Medicina, Universitat d'Alacant, Spain.}, Pages = {1465-78}, Pubmed = {7506971}, Title = {Organization of auditory callosal connections in hypothyroid adult rats}, Uuid = {BEADEFD2-1B46-4E2C-881A-B37C95181BBD}, Volume = {5}, Year = {1993}} @article{Berbel:1988, Abstract = {Changes in the size and shape of the corpus callosum (CC)--and in number, size, and structure of callosal axons--between embryonic day 38 (E38) and postnatal day 150 (P150) were studied by light and electron microscope in 25 kittens. The development of the CC was divided into three phases: 1. Embryonic development (E38, 53, 58): At E38, only part of the body of the CC was formed. At E53 and E58, the CC was still very short, but its different parts (genu, body, and splenium) had formed. The cross-sectional callosal area (CCA) was 5.4 mm2 at E53 and 5.6 mm2 at E58. The CC contained 46.3 and 56.4 million axons at E53 and E58 respectively. Mean axon diameters were 0.26 micron at E53 and 0.27 micron at E58. 2. Early postnatal development (P4, 9, 15, 18, 21, 26): The CC at P4 was much longer than at E58 and still slightly elongated during this phase; CCA reached 8.55 mm2 at P4 and 8.88 mm2 at P26. There was a substantial axonal loss (66.8 million at P4 and 52.6 million at P26). From P15 onward, premyelinated and myelinated axons were seen. Mean axon diameter increased from 0.30 micron at P4 to 0.33 micron at P26. 3. Late postnatal development (P39, 57, 92, 107, 150). The CC grew dramatically in both length and thickness, the latter especially in the genu. CCA was 10.1 mm2 at P39 and 15.3 mm2 at P150. The number of axons still decreased (46.5 million at P39 and 31.9 million at P150). The growth of the CCA paralleled the increase of myelinated axons (0.5\%at P26 and 29.6\%at P150 and in the mean axon diameters (0.34 micron at P39 and 0.42 micron at P150). A number of axonal ultrastructural peculiarities (electron-dense bodies, large vacuoles, lamellated bodies, etc., including those mentioned below) were noticed; their frequency at different ages was estimated as the percent of total axons. Interestingly, accumulations of vesicles inside axons increased from 4.1\%at E53 to 8.9\%at P26, dropped to 0.2\%at P39, and remained below 1\%thereafter. Swollen mitochondria increased from 0.2\%at E53 to 0.9\%at P26 and dropped to 0.06\%(on the average) from P39 onward. Accumulations of vesicles and swollen mitochondria increased during the phase of rapid axonal elimination; thus, they may indicate axonal retraction and/or degeneration. Microglia-gitter cells and astrocytes showing signs of phagocytosis were found during the embryonic and early postnatal development and may be involved in axon elimination.}, Author = {Berbel, P. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Aging;Embryo and Fetal Development;Corpus Callosum;Cats;Microscopy, Electron;Not relevant;Cell Count;11 Glia;Support, Non-U.S. Gov't;Nerve Fibers, Myelinated;Animals;Axons}, Medline = {89054473}, Month = {10}, Nlm_Id = {0406041}, Number = {1}, Organization = {Institute of Anatomy, Lausanne, Switzerland.}, Pages = {132-56}, Pubmed = {3192762}, Title = {The development of the corpus callosum in cats: a light- and electron-microscopic study}, Uuid = {E5D0AC39-1A39-483D-BA0A-5BEF0F0C6C31}, Volume = {276}, Year = {1988}} @article{Bergeron:1969, Author = {Bergeron, R. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0567-8056}, Journal = {Acta Radiol Diagn (Stockh)}, Keywords = {21 Epilepsy;21 Neurophysiology;Female;Pneumoencephalography;Cerebral Ventriculography;Autopsy;Pregnancy;Humans;Abnormalities;24 Pubmed search results 2008;Cerebral Cortex;Brain}, Medline = {70163597}, Nlm_Id = {0370367}, Pages = {135-9}, Pubmed = {5309644}, Title = {Radiographic demonstration of cortical heterotopia}, Uuid = {9A0CA96B-18C9-4D97-B729-02E1B42C4CF3}, Volume = {9}, Year = {1969}} @article{Berman:1997, Abstract = {Radial glia are present at the earliest stage of cerebral cortical development, and later they transform into astrocytes. Other glial cells including astrocytes and oligodendrocytes are thought to appear only after neuron generation is complete and the cortical layers are formed. Little is known of when and where microglia enter the central nervous system and proliferate. We addressed the question of the origin of these three glial cell types in the developing ferret cerebral cortex. We assessed the temporal pattern of glial cell division by administering [3H]thymidine to label cells in S phase, and by using survival periods of 1-2 h to label dividing cells in situ. Labeled cells were identified in the developing intermediate zone of the ferret cerebral wall. These cells were present at E28, and reached a maximum number at P1. Double labeling experiments identified these cells as astrocytes, oligodendrocytes or microglia. None of the dividing cells expressed neuronal markers. These data show that all three types of glia are generated in the developing subcortical white matter, and that glial progenitors are present in the intermediate zone as soon as it becomes a recognizable structure. These data also show that the period of glial generation overlaps extensively with the period of neuron generation, since neuron generation is not complete until the end of the second postnatal week in the ferret.}, Author = {Berman, N. E. and Johnson, J. K. and Klein, R. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Neuroglia/metabolism/*physiology;Pregnancy;G;Cerebral Cortex/*cytology/*growth &development/metabolism;Bromodeoxyuridine/pharmacology;Thymidine/metabolism;Microglia/physiology;Phenotype;Female;Cell Count;Animal;11 Glia;Antimetabolites/pharmacology;Support, U.S. Gov't, P.H.S.;Animals, Newborn/physiology;Immunohistochemistry;Biological Markers;Ferrets/*physiology}, Number = {1-2}, Organization = {Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160-7400, USA. Nberman\@knmc.edu}, Pages = {149-64.}, Title = {Early generation of glia in the intermediate zone of the developing cerebral cortex}, Uuid = {15C29F53-C9A7-4940-894B-463DD275E459}, Volume = {101}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9263589}} @article{Bernad:1994, Abstract = {An efficient procedure for the insertion of genetic markers into a large proportion of the mouse haemopoietic system was developed, based on the in vitro expansion of retrovirally infected bone marrow and selection of the transduced cells. Bone marrow cells harvested 4 d after 5-FU treatment were incubated under IL-3/SCF stimulation and their growth dynamic, susceptibility to retroviral infection and reconstitution capacity evaluated throughout the incubation period. On the third day of culture a maximum expansion in the CFU-GM and CFU-S12 progenitor pools was observed (130- and 15-fold, respectively), with no apparent impairment in long-term repopulating precursors. This expansion was, however, accompanied by a net decrease in the CFU-GM susceptibility to the infection by supernatants containing a Moloney-derived ecotropic retroviral vector carrying the neor gene. The designed protocol thus involved the infection of freshly harvested 5-FU-treated bone marrow, followed by expansion under IL-3/SCF stimulation and selection for resistance to G418. This procedure allowed us to harvest up to 780 CFU-GM and 50 CFU-S12 per 10(5) bone marrow cells, free from non-genetically marked progenitors. Most of the animals reconstituted with the transduced marrow bore, for at least 5 months, a very high proportion of bone marrow, spleen and thymus cells tagged with the reporter gene. These results, together with the high percentage of haemopoietic precursors bearing the neor gene and expressing resistance to G418 5 months after the transplantation indicates that long-term lympho-haemopoietic repopulating cells were efficiently transduced and selected in vitro under conditions that preserve their self-renewal and differentiation properties. This gene-transfer methodology may improve the development of gene therapy protocols where the purging of non-transduced precursors would guarantee a lasting and uniform expression of exogenous genes.}, Author = {Bernad, A. and Varas, F. and Gallego, J. M. and Almendral, J. M. and Bueren, J. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0007-1048}, Journal = {Br J Haematol}, Keywords = {Mice, Inbred BALB C;Animals;Hematopoietic Cell Growth Factors;Cells, Cultured;Bone Marrow Transplantation;Recombinant Proteins;Female;Interleukin-3;Mice, Inbred C57BL;Disease Susceptibility;11 Glia;Retroviridae;Genetic Vectors;Blotting, Southern;Male;Bone Marrow Cells;Retroviridae Infections;Gene Transfer Techniques;Mice;Hematopoietic Stem Cells;Stem Cell Factor;Research Support, Non-U.S. Gov't}, Medline = {95034235}, Month = {5}, Nlm_Id = {0372544}, Number = {1}, Organization = {Unidad de Biolog{\'\i}a Molecular y Celular, CIEMAT, Madrid, Spain.}, Pages = {6-17}, Pubmed = {7524619}, Title = {Ex vivo expansion and selection of retrovirally transduced bone marrow: an efficient methodology for gene-transfer to murine lympho-haemopoietic stem cells}, Uuid = {28C4E4E0-8EC7-486F-9950-1845A717E5B1}, Volume = {87}, Year = {1994}} @article{Bernier:2002, Abstract = {The subventricular zone remains mitotically active throughout life in rodents. Studies with tritiated thymidine, which is incorporated into the DNA of mitotic cells, have revealed that the rodent subventricular zone produces neuroblasts that migrate toward the olfactory bulb along the rostral migratory stream. A similar migratory stream has been documented in monkeys by using the thymidine analogue BrdUrd. The same approach showed that neurogenesis occurred in the dentate gyrus of adult primates, including humans. In the present study, experiments combining injections of BrdUrd and the dye 1,1'-dioctadecyl-3,3,3',3'-tetramethylindo-carbocyanine, with the immunostaining for molecular markers of neurogenesis (polysialylated neural cell adhesion molecule, beta-tubulin-III, collapsin response mediator protein-4, neuronal nuclear protein) in New World (Saimiri sciureus) and Old World (Macaca fascicularis) monkeys have revealed that new neurons are produced in the amygdala, piriform cortex, and adjoining inferior temporal cortex in adult primates. These newborn neurons expressed the antiapoptotic protein Bcl-2 and formed a more-or-less continuous pathway that extended from the tip of the temporal ventricular horn to the deep portion of the temporal lobe. The production of newborn neurons in the amygdala, piriform cortex, and inferior temporal cortex seems to parallel the continuing addition of neurons in the olfactory bulb. These two concomitant phenomena may ensure structural stability and functional plasticity to the primate olfactory system and temporal lobe. 22177226 0027-8424 Journal Article}, Author = {Bernier, P. J. and Bedard, A. and Vinet, J. and Levesque, M. and Parent, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;A both}, Number = {17}, Organization = {Centre de Recherche Universite Laval-Robert-Giffard, 2601, Chemin de la Canardiere, Local F-6500, Beauport, QC, Canada G1J 2G3.}, Pages = {11464-9}, Title = {Newly generated neurons in the amygdala and adjoining cortex of adult primates}, Uuid = {F334D8FC-CDEF-11D9-B244-000D9346EC2A}, Volume = {99}, Year = {2002}, url = {papers/Bernier_ProcNatlAcadSciUSA2002.pdf}} @article{Berns:2004, Abstract = {RNA interference (RNAi) is a powerful new tool with which to perform loss-of-function genetic screens in lower organisms and can greatly facilitate the identification of components of cellular signalling pathways. In mammalian cells, such screens have been hampered by a lack of suitable tools that can be used on a large scale. We and others have recently developed expression vectors to direct the synthesis of short hairpin RNAs (shRNAs) that act as short interfering RNA (siRNA)-like molecules to stably suppress gene expression. Here we report the construction of a set of retroviral vectors encoding 23,742 distinct shRNAs, which target 7,914 different human genes for suppression. We use this RNAi library in human cells to identify one known and five new modulators of p53-dependent proliferation arrest. Suppression of these genes confers resistance to both p53-dependent and p19ARF-dependent proliferation arrest, and abolishes a DNA-damage-induced G1 cell-cycle arrest. Furthermore, we describe siRNA bar-code screens to rapidly identify individual siRNA vectors associated with a specific phenotype. These new tools will greatly facilitate large-scale loss-of-function genetic screens in mammalian cells.}, Author = {Berns, Katrien and Hijmans, E. Marielle and Mullenders, Jasper and Brummelkamp, Thijn R. and Velds, Arno and Heimerikx, Mike and Kerkhoven, Ron M. and Madiredjo, Mandy and Nijkamp, Wouter and Weigelt, Britta and Agami, Reuven and Ge, Wei and Cavet, Guy and Linsley, Peter S. and Beijersbergen, Roderick L. and Bernards, Ren{\'e}}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {RNA, Small Interfering;Genetic Vectors;Down-Regulation;Gene Library;p14ARF Protein;Human;Cell Line, Tumor;Retroviridae;Cell Division;Cyclins;RNA Interference;23 RNAi;Reproducibility of Results;Protein p53;Cloning, Molecular;23 Technique;Fibroblasts}, Month = {3}, Nlm_Id = {0410462}, Number = {6981}, Organization = {Division of Molecular Carcinogenesis and Center for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.}, Pages = {431-7}, Pii = {nature02371}, Pubmed = {15042092}, Title = {A large-scale RNAi screen in human cells identifies new components of the p53 pathway}, Uuid = {B4BD274A-63B0-4649-B973-4BD3490A264D}, Volume = {428}, Year = {2004}, url = {papers/Berns_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature02371}} @article{Berry:1965, Abstract = {0021-8782 Journal Article}, Author = {Berry, M. and Rogers, A. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Anat}, Keywords = {Thymidine;Fetus;Female;Rats;Autoradiography;Microscopy, Phase-Contrast;In Vitro;A,F abstr;Pregnancy;Cerebral Cortex/*cytology/*embryology;Tritium;Animals;Male;Microscopy}, Number = {4}, Pages = {691-709}, Pubmed = {5325778}, Title = {The migration of neuroblasts in the developing cerebral cortex}, Uuid = {2A0FC626-CDF0-11D9-B244-000D9346EC2A}, Volume = {99}, Year = {1965}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5325778}} @article{Berry:2002, Abstract = {We present evidence that NG2+ glia are an integral part of an oligodendrocyte/synantocyte (OS) lineage stream the progenitors of which begin to produce both glial phenotypes at about birth. The NG2 CSPG is differentially distributed within the OS lineage, being expressed in progenitors and synantocytes but not in oligodendrocytes. All cells in the OS lineage, except the primordial stem cells, express O4. The oligodendrocyte line reacts with CD9, but synantocytes are CD9-. Nonetheless, synantocytes are morphologically complex and specialised glia which contact axolemma in myelinated fibres at nodes of Ranvier and synaptic terminals, and form >99\%of all NG2+ glia in the adult CNS. Thus, the other NG2+ phenotype, the adult oligodendrocyte progenitor cell (AOPC), constitutes a small population of <1\%of all NG2+ glia in the mature CNS. AOPC are a heterogeneous set of cells probably originating from multiple sources which, by definition, produce oligodendrocytes in the adult to replace loss after trauma, demyelination and normal 'wear and tear'. The definitive functions of synantocytes remain undefined. 0300-4864 Journal Article}, Author = {Berry, M. and Hubbard, P. and Butt, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurocytol}, Keywords = {11 Glia;G pdf}, Number = {6-7}, Organization = {Neural Damage and Repair, Centre for Neuroscience Research, Hodgkin Building, GKT School of Biomedical Sciences, Guy's Campus, London Bridge, London SE1 1UL, UK. martin.berry\@kcl.ac.uk}, Pages = {457-67}, Pubmed = {14501216}, Title = {Cytology and lineage of NG2-positive glia}, Uuid = {21E0C200-2C7E-4B96-B2C6-40F21160868E}, Volume = {31}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14501216}} @article{Bertolotto:1993, Abstract = {We used six monoclonal antibodies (MAb) recognizing epitopes within keratan sulfate (KS) chains for an immunocytochemical study of adult rat brain. One of the MAb selectively stained microglia and their ramified processes. KS-positive cells were found throughout the CNS in both paraffin-embedded and cryostat sections; the greatest number were present in hippocampus and brainstem. In the cortex the positive processes of some cells surrounded neuronal somata. In the white matter the processes were both parallel and perpendicular to the axon bundles. Double staining showed that KS-positive cells did not express astrocytic or oligodendroglial markers. By immunoelectron microscopy, the positivity was localized around the perikarya and cell processes of small cells with peripheral chromatin clumps and dark cytoplasm, which often contained secondary lysosomes. The KS-positive cells did not contribute to myelin sheaths and were not surrounded by a basal membrane. In addition to the cellular staining, three other MAb stained the white matter diffusely. Anti-KS MAb are therefore proposed as immunohistochemical markers for ramified microglia in both paraffin and cryostat sections of adult rat brain.}, Author = {Bertolotto, A. and Caterson, B. and Canavese, G. and Migheli, A. and Schiffer, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0022-1554}, Journal = {J Histochem Cytochem}, Keywords = {Support, Non-U.S. Gov't;Paraffin Embedding;Brain Chemistry;Keratan Sulfate;Neuroglia;Rats;Antibodies, Monoclonal;Not relevant;11 Glia;Frozen Sections;Fluorescent Antibody Technique;Peptide Hydrolases;Microscopy, Immunoelectron;Brain;Immunoenzyme Techniques;Animals}, Medline = {93195291}, Month = {4}, Nlm_Id = {9815334}, Number = {4}, Organization = {Clinica Neurologica II, Universit\`{a}di Torino, Italy.}, Pages = {481-7}, Pubmed = {8450191}, Title = {Monoclonal antibodies to keratan sulfate immunolocalize ramified microglia in paraffin and cryostat sections of rat brain}, Uuid = {BF823A1A-292A-4512-A7DE-1ECD161530DF}, Volume = {41}, Year = {1993}, url = {papers/Bertolotto_JHistochemCytochem1993.pdf}} @article{Besancon:1981, Abstract = {0006-291x Journal Article}, Author = {Besancon, F. and Bourgeade, M. F. and Justesen, J. and Ferbus, D. and Thang, M. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Biochem Biophys Res Commun}, Keywords = {Cell Transformation, Viral/*drug effects;2',5'-Oligoadenylate Synthetase;Mice, Inbred BALB C;Nucleotidyltransferases/*metabolism;Interferons/pharmacology;Kinetics;EE, DMSO, abstr;Cell Line;08 Aberrant cell cycle;Moloney murine leukemia virus/*genetics;Dimethyl Sulfoxide/*pharmacology;Cell Differentiation/drug effects;Support, Non-U.S. Gov't;Animals;Mice;Butyrates/*pharmacology}, Number = {1}, Pages = {16-24}, Pubmed = {6172125}, Title = {Two inducers of cell differentiation enhance the 2'5'oligoadenylate synthetase activity in MSV transformed cells}, Uuid = {AA6A7ABE-4D9C-43F6-9C7F-65E4DB0679B7}, Volume = {103}, Year = {1981}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6172125}} @article{Beschorner:2002, Abstract = {The immune response in the central nervous system (CNS) is under tight control of regulatory mechanisms, resulting in the establishment of immune privilege. CNS injury induces an acute inflammatory reaction, composed mainly of invading leukocytes and activated microglial cells/macrophages. The generation of this robust immune response requires binding of receptors such as CD14, a pattern recognition receptor of the immune system. CD14, a surface molecule of monocytic cells, is up-regulated after monocyte stimulation and is involved in cellular activation. To examine CD14 expression in human brain lesions we investigated sections of brains obtained at autopsy from 25 cases following closed traumatic brain injury (TBI) and 5 control brains by immunohistochemistry. Detection of CD14 in controls demonstrated constitutive expression by perivascular cells, but not in parenchymal microglial cells, equivalent to known expression pattern of ED2 in rats. Following TBI, numbers of CD14(+) cells in perivascular spaces and in the brain parenchyma increased in parallel within 1-2 days, both at the lesion and in adjacent perilesional areas. The number of CD14(+) cells in perivascular spaces and in the brain parenchyma reached maximum levels within 4-8 days and remained elevated until weeks after trauma. In contrast to activated parenchymal microglia/macrophages, resting parenchymal microglial cells lacked CD14. Thus, early CD14 expression constitutes an essential part of the acute inflammatory CNS response following trauma.}, Author = {Beschorner, Rudi and Nguyen, Thai D. and G{\"o}zalan, Fatma and Pedal, Ingo and Mattern, Rainer and Schluesener, Hermann J. and Meyermann, Richard and Schwab, Jan M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Research Support, Non-U.S. Gov't;Adolescent;Monocytes;Antigens, Differentiation, Myelomonocytic;Middle Aged;Macrophages;Humans;Brain;Antigens, Differentiation;Female;Cell Membrane;Extracellular Space;Antigens, CD;Microglia;11 Glia;Chemotaxis, Leukocyte;Antigens, CD14;Male;Calgranulin A;Brain Injuries;Aged;Aged, 80 and over;Calcium-Binding Proteins;Adult;Immunohistochemistry;Histocompatibility Antigens Class II;Blood Vessels}, Medline = {22005489}, Month = {6}, Nlm_Id = {0412041}, Number = {6}, Organization = {Institute of Brain Research, University of T{\"u}bingen, Medical School, Calwerstr. 3, 72076, Germany. rudi.beschorner\@med.uni-tuebingen.de}, Pages = {541-9}, Pubmed = {12012085}, Title = {CD14 expression by activated parenchymal microglia/macrophages and infiltrating monocytes following human traumatic brain injury}, Uuid = {A20AECDF-C0BD-4D7F-BF5F-CD5F3186706F}, Volume = {103}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00401-001-0503-7}} @article{Beshel:2007, Abstract = {Fast oscillations in neural assemblies have been proposed as a mechanism to facilitate stimulus representation in a variety of sensory systems across animal species. In the olfactory system, intervention studies suggest that oscillations in the gamma frequency range play a role in fine odor discrimination. However, there is still no direct evidence that such oscillations are intrinsically altered in intact systems to aid in stimulus disambiguation. Here we show that gamma oscillatory power in the rat olfactory bulb during a two-alternative choice task is modulated in the intact system according to task demands with dramatic increases in gamma power during discrimination of molecularly similar odorants in contrast to dissimilar odorants. This elevation in power evolves over the course of criterion performance, is specific to the gamma frequency band (65-85 Hz), and is independent of changes in the theta or beta frequency band range. Furthermore, these high amplitude gamma oscillations are restricted to the olfactory bulb, such that concurrent piriform cortex recordings show no evidence of enhanced gamma power during these high-amplitude events. Our results display no modulation in the power of beta oscillations (15-28 Hz) shown previously to increase with odor learning in a Go/No-go task, and we suggest that the oscillatory profile of the olfactory system may be influenced by both odor discrimination demands and task type. The results reported here indicate that enhancement of local gamma power may reflect a switch in the dynamics of the system to a strategy that optimizes stimulus resolution when input signals are ambiguous.}, Author = {Beshel, Jennifer and Kopell, Nancy and Kay, Leslie M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Odors;Electroencephalography;Olfactory Pathways;Biological Clocks;21 Neurophysiology;Rats, Sprague-Dawley;Discrimination Learning;Rats;Smell;Psychomotor Performance;comparative study;research support, n.i.h., extramural;Olfactory Bulb;Animals;Male;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {31}, Organization = {Department of Psychology and Institute for Mind and Biology, The University of Chicago, Chicago, Illinois 60637, USA.}, Pages = {8358-65}, Pii = {27/31/8358}, Pubmed = {17670982}, Title = {Olfactory bulb gamma oscillations are enhanced with task demands}, Uuid = {DDD06710-1E27-4EA9-9DA9-3AB51BC916A1}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1199-07.2007}} @article{Bessis:2007, Abstract = {Microglia have long been characterized by their immune function in the nervous system and are still mainly considered in a beneficial versus detrimental dialectic. However a review of literature enables to shed novel lights on microglial function under physiological conditions. It is now relevant to position these cells as full time partners of neuronal function and more specifically of synaptogenesis and developmental apoptosis. Indeed, microglia can actively control neuronal death. It has actually been shown in retina that microglial nerve growth factor (NGF) is necessary for the developmental apoptosis to occur. Similarly, in cerebellum, microglia induces developmental Purkinje cells death through respiratory burst. Furthermore, in spinal cord, microglial TNFalpha commits motoneurons to a neurotrophic dependent developmental apoptosis. Microglia can also control synaptogenesis. This is suggested by the fact that a mutation in KARAP/DAP12, a key protein of microglial activation impacts synaptic functions in hippocampus, and synapses protein content. In addition it has been now demonstrated that microglial brain-derived neurotrophin factor (BDNF) directly regulates synaptic properties in spinal cord. In conclusion, microglia can control neuronal function under physiological conditions and it is known that neuronal activity reciprocally controls microglial activation. We will discuss the importance of this cross-talk which allows microglia to orchestrate the balance between synaptogenesis and neuronal death occurring during development or injuries. (c) 2006 Wiley-Liss, Inc.}, Author = {Bessis, Alain and B{\'e}chade, Catherine and Bernard, Delphine and Roumier, Anne}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8806785}, Number = {3}, Organization = {Biologie Cellulaire de la Synapse, Inserm U789, Ecole Normale Sup{\'e}rieure, 46 rue d'Ulm 75005 Paris, France.}, Pages = {233-8}, Pubmed = {17106878}, Title = {Microglial control of neuronal death and synaptic properties}, Uuid = {45C5A73E-0932-4090-ABF9-C60B4DFD984A}, Volume = {55}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20459}} @article{Bessis:2005, Abstract = {Tumor necrosis factor-alpha (TNFalpha) is a prototypic inflammatory cytokine up-regulated in most if not all neurodegenerative diseases. Many studies have reported variable roles in the adult or pathological brain. In contrast, the implication of TNFalpha in developmental neuronal cell death has been well documented in few studies. In sympathetic and trigeminal neurons, TNFalpha acts in an autocrine manner to induce immediate cell death on neurotrophic factor deprivation. In the spinal cord, TNFalpha is transiently produced by macrophages and commits motoneurons to become competent to die 2 days later. TNFalpha is also likely to induce immediate and delayed prodeath effects in adult and pathological tissues. Data obtained in embryonic systems will thus help to develop new therapeutic approaches to pathological neuronal death in adults.}, Author = {Bessis, Alain and Bernard, Delphine and Triller, Antoine}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1073-8584}, Journal = {Neuroscientist}, Keywords = {10 Development;11 Glia}, Month = {8}, Nlm_Id = {9504819}, Number = {4}, Organization = {Laboratoire de Biologie Cellulaire de la Synapse Normale et Pathologique. alain.bessis\@ens.fr.}, Pages = {277-81}, Pii = {11/4/277}, Pubmed = {16061514}, Title = {Tumor Necrosis Factor-\{alpha\}and Neuronal Development}, Uuid = {48CC8928-A33C-495B-AEB1-6C3EE4A5949F}, Volume = {11}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1177/1073858404270905}} @article{Betarbet:1996, Abstract = {Our previous studies have shown that the progeny of the neuronal progenitor cells localized in a discrete region of the anterior part of the neonatal subventricular zone, referred to as the SVZa, migrate tangentially along a stereotypical and extended pathway to the olfactory bulb, and then turn radially into one of the overlying cellular layers. In this study we have examined whether the SVZa cells retain their ability to migrate and disperse when heterotopically transplanted into the striatum. SVZa cells from P0-P2 rat pups were microdissected, dissociated, labeled with the lipophilic, fluorescent dye PKH26 or the cell proliferation marker BrdU, and then transplanted into the neonatal (P0-P2) striatum. Examination of the striatum a few days after transplantation revealed aggregates of heavily labeled BrdU- positive, SVZa cells in the striatum, often situated near blood vessels. Two to four weeks after transplantation, however, the labeled SVZa cells had disseminated from their site of implantation and showed three patterns of distribution. In none of the cases was the implantation site detectable in the striatum, signifying that the cells had become incorporated in the host brain. Of the 12 brains analyzed for cell distribution, transplanted SVZa cells were confined to the striatum in 4 cases. The cells were present as individual cells or in small groups of usually two to four cells. When PKH26 was used, we found that many of the transplanted cells extended processes into the striatum. In 3 out of the 12 animals, the labeled SVZa cells were distributed along the dorsal and lateral aspects of the striatal boundary. In the remaining five animals, labeled SVZa cells appeared in both locations: within the striatum as well as along the striatal boundary. The dispersion of the transplanted cells within the striatum and the presence of the transplanted SVZa cells all along the striatal boundary, a region corresponding to the lateral cortical stream of migration of the developing forebrain, demonstrates that the isochronically transplanted SVZa cells retained their capacity to migrate.}, Author = {Betarbet, R. and Zigova, T. and Bakay, R. A. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cell Transplant}, Keywords = {Fluorescent Dyes;Microinjections;Rats;Cell Movement/*physiology;Female;Animal;Rats, Sprague-Dawley;Stem Cells/*cytology/*transplantation;Retroviridae;*Transplantation, Heterotopic;17 Transplant Regeneration;Cell Survival/physiology;Male;Animals, Newborn;Support, Non-U.S. Gov't;L abstr;Neostriatum;Support, U.S. Gov't, P.H.S.;Cerebral Cortex/cytology;Immunohistochemistry;Bromodeoxyuridine}, Number = {2}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.}, Pages = {165-78.}, Title = {Migration patterns of neonatal subventricular zone progenitor cells transplanted into the neonatal striatum}, Uuid = {16AE466F-4B4A-48A3-9BA4-F2E7E13A948D}, Volume = {5}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8689029}} @article{Betarbet:1996a, Abstract = {Earlier studies in our laboratory have demonstrated that a discrete region of the anterior part of the neonatal subventricular zone (SVZa) contains exclusively neuronal progenitor cells. The descendants of the SVZa progenitor cells are destined for the granule cell and glomerular layers of the olfactory bulb, where they differentiate into granule and periglomerular cells, the interneurons of the olfactory bulb, respectively. In the present set of experiments we examined the neurotransmitter phenotype of the SVZa-derived cells. In order to label SVZa-derived cells, the cell proliferation marker bromodeoxyuridine (BrdU) was injected into the SVZa of postnatal day 2 (P2) rats. After 3 weeks, by which time most of the SVZa-derived cells have migrated to their final destination in the bulb, the animals were perfused and their brains processed for immunohistochemistry. To identify the neurotransmitter phenotype of the SVZa-derived cells, sagittal sections of the forebrain, including the olfactory bulb, were double-labeled with an antibody to BrdU in conjunction with an antibody to gamma-amino- butyric acid (GABA) or tyrosine hydroxylase (TH), the rate limiting enzyme in the synthesis of dopamine. Using simultaneous indirect immunofluorescence to detect the presence of single- and double-labeled cells, we found that 59\%and 51\%of the BrdU-positive cells were immunoreactive for GABA in the granule cell and glomerular layers, respectively. In addition, 10\%of the BrdU-positive periglomerular cells were immunoreactive for TH. The presence of double-labeled (BrdU- positive/GABA-positive and BrdU-positive/TH-positive) cells in the olfactory bulb, demonstrates that the SVZa is a source of the GABAergic and dopaminergic interneurons of the olfactory bulb during postnatal development.}, Author = {Betarbet, R. and Zigova, T. and Bakay, R. A. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:16:09 -0400}, Journal = {Int J Dev Neurosci}, Keywords = {I both;Brain/cytology/embryology;Tyrosine 3-Monooxygenase/analysis;Rats, Sprague-Dawley;13 Olfactory bulb anatomy;Female;Rats;Cerebral Ventricles/embryology;Animal;Animals, Newborn;Support, U.S. Gov't, P.H.S.;gamma-Aminobutyric Acid/*analysis;Support, Non-U.S. Gov't;Dopamine/*analysis;Interneurons/chemistry/*cytology;Male;Cell Lineage}, Number = {7-8}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta GA 30322, USA.}, Pages = {921-30.}, Title = {Dopaminergic and GABAergic interneurons of the olfactory bulb are derived from the neonatal subventricular zone}, Uuid = {16EC1042-E17A-4285-8B41-6C3A41A74A90}, Volume = {14}, Year = {1996}, url = {papers/Betarbet_IntJDevNeurosci1996.pdf}} @article{Betschinger:2003, Abstract = {To generate different cell types, some cells can segregate protein determinants into one of their two daughter cells during mitosis. In Drosophila neuroblasts, the Par protein complex localizes apically and directs localization of the cell fate determinants Prospero and Numb and the adaptor proteins Miranda and Pon to the basal cell cortex, to ensure their segregation into the basal daughter cell. The Par protein complex has a conserved function in establishing cell polarity but how it directs proteins to the opposite side is unknown. We show here that a principal function of this complex is to phosphorylate the cytoskeletal protein Lethal (2) giant larvae (Lgl; also known as L(2)gl). Phosphorylation by Drosophila atypical protein kinase C (aPKC), a member of the Par protein complex, releases Lgl from its association with membranes and the actin cytoskeleton. Genetic and biochemical experiments show that Lgl phosphorylation prevents the localization of cell fate determinants to the apical cell cortex. Lgl promotes cortical localization of Miranda, and we propose that phosphorylation of Lgl by aPKC at the apical neuroblast cortex restricts Lgl activity and Miranda localization to the opposite, basal side of the cell. 0028-0836 Journal Article}, Author = {Betschinger, J. and Mechtler, K. and Knoblich, J. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Nature}, Keywords = {Cell Cycle Proteins/metabolism;10 Development;Proteins/*metabolism;Animals;Phosphorylation;Cytoskeleton/*metabolism;Protein Transport;Cell Line;Support, Non-U.S. Gov't;Carrier Proteins/metabolism;Macromolecular Systems;Drosophila Proteins/*metabolism;Protein Kinase C/*metabolism;Drosophila melanogaster/*cytology/*metabolism;Molecular Sequence Data;Cell Division;Amino Acid Sequence;*Cell Polarity;F}, Number = {6929}, Organization = {Research Institute of Molecular Pathology, Dr Bohr Gasse 7, 1030 Vienna, Austria.}, Pages = {326-30}, Pubmed = {12629552}, Title = {The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl}, Uuid = {819657AE-CF7F-4E49-ADE9-B1F30F5A6CA6}, Volume = {422}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12629552}} @article{Betzig:2006, Abstract = {We introduce a method for optically imaging intracellular proteins at nanometer spatial resolution. Numerous sparse subsets of photoactivatable fluorescent protein molecules were activated, localized (to approximately 2 to 25 nanometers), and then bleached. The aggregate position information from all subsets was then assembled into a superresolution image. We used this method--termed photoactivated localization microscopy--to image specific target proteins in thin sections of lysosomes and mitochondria; in fixed whole cells, we imaged vinculin at focal adhesions, actin within a lamellipodium, and the distribution of the retroviral protein Gag at the plasma membrane.}, Author = {Betzig, Eric and Patterson, George H. and Sougrat, Rachid and Lindwasser, O. Wolf and Olenych, Scott and Bonifacino, Juan S. and Davidson, Michael W. and Lippincott-Schwartz, Jennifer and Hess, Harald F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Fluorescence;Lysosomes;research support, n.i.h., extramural ;Organelles;HIV-1;Animals;Photobleaching;Algorithms;Proteins;Mitochondria;Cercopithecus aethiops;Cell Membrane;Focal Adhesions;COS Cells;23 Technique;Recombinant Fusion Proteins;Gene Products, gag;Cell Line;Nanotechnology;Light;Vinculin;Microscopy;24 Pubmed search results 2008;Actins;Luminescent Proteins;Pseudopodia}, Month = {9}, Nlm_Id = {0404511}, Number = {5793}, Organization = {Howard Hughes Medical Institute, Janelia Farm Research Campus, Ashburn, VA 20147, USA. betzige\@janelia.hhmi.org}, Pages = {1642-5}, Pii = {1127344}, Pubmed = {16902090}, Title = {Imaging intracellular fluorescent proteins at nanometer resolution}, Uuid = {ACD71C04-1337-4A14-9EEF-FAA299BE64FA}, Volume = {313}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1127344}} @article{Belanger:1997, Abstract = {In the embryonic CNS, preformed pathways precede the growth of axonal fasciculi [Katz M. J. and Lasek R. J. (1980) Cell Motil. 1, 141-157; Katz M. J. et al. (1980) Neuroscience 5, 821-833]. What are the developmental events that lead to the elaboration of these preformed pathways? To answer this question, we investigated the organization of the primitive neural tube and more particularly the arrangement of the early-generated cells using [3H]thymidine autoradiography or bromodeoxyuridine. Our data suggest that the position of early-generated cells might be involved in the setting of such pathways. In the brain stem of E12(0) (12 days and 0 h) and E12(15) rat embryos, the first-generated cells were organized into three longitudinal columns associated with glycoconjugate-rich extracellular spaces in the adjacent primitive marginal layer. Also, axons traced with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) were contiguous to the early-generated cellular columns and represented the primordium of the medial longitudinal fasciculus, the lateral longitudinal tract and the mesencephalic trigeminal tract. Our results show a correlation between the organization of early-generated cells, likely neurons, and the pattern of extracellular spaces in the marginal layer where axons grow. It has been reported in the literature that neurons produce elements of the extracellular matrix such as growth-modulating molecules or space-creating molecules. We therefore suggest that the position of early-generated neurons could be involved in the elaboration of a template for the setting of some major longitudinal tracts during embryonic development of the brainstem.}, Author = {B{\'e}langer, M. C. and Auclair, F. and Bertrand, L. and Marchand, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Thymidine;24 Pubmed search results 2008;Brain Stem;Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;Female;Carbocyanines;Neural Pathways;Rats;Fluorescent Dyes;Pregnancy;Histocytochemistry;Animals;Antimetabolites;Bromodeoxyuridine;Neurons;Axons}, Medline = {97280779}, Month = {5}, Nlm_Id = {7605074}, Number = {1}, Organization = {Universit{\'e} Laval and Centre de Recherche en Neurobiologie, H\^{o}pital del'Enfant-J{\'e}sus, Qu{\'e}bec, Canada.}, Pages = {259-70}, Pii = {S0306452296004848}, Pubmed = {9135106}, Title = {The early neuronal organization predicts the path followed by some major axonal bundles in the embryonic brainstem}, Uuid = {FD3759D4-0620-464D-8050-1B2803BE2ACC}, Volume = {78}, Year = {1997}} @article{Bhandawat:2005, Abstract = {Signaling by heterotrimeric GTP-binding proteins (G proteins) drives numerous cellular processes. The number of G protein molecules activated by a single membrane receptor is a determinant of signal amplification, although in most cases this parameter remains unknown. In retinal rod photoreceptors, a long-lived photoisomerized rhodopsin molecule activates many G protein molecules (transducins), yielding substantial amplification and a large elementary (single-photon) response, before rhodopsin activity is terminated. Here we report that the elementary response in olfactory transduction is extremely small. A ligand-bound odorant receptor has a low probability of activating even one G protein molecule because the odorant dwell-time is very brief. Thus, signal amplification in olfactory transduction appears fundamentally different from that of phototransduction.}, Author = {Bhandawat, Vikas and Reisert, Johannes and Yau, King-Wai W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Dose-Response Relationship, Drug;Signal Transduction;Rana pipiens;Animals;In Vitro;Cell Separation;Olfactory Receptor Neurons;Phosphorylation;Cyclohexanols;Kinetics;Heterotrimeric GTP-Binding Proteins;Calcium;Odors;Smell;Monoterpenes;Research Support, U.S. Gov't, P.H.S.;Action Potentials;Acetophenones;Receptors, Odorant;24 Pubmed search results 2008;Adenylate Cyclase;Research Support, N.I.H., Extramural;Ligands;Research Support, Non-U.S. Gov't}, Month = {6}, Nlm_Id = {0404511}, Number = {5730}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. vbhanda\@mail.jhmi.edu}, Pages = {1931-4}, Pii = {308/5730/1931}, Pubmed = {15976304}, Title = {Elementary response of olfactory receptor neurons to odorants}, Uuid = {528CEC99-177D-4360-9CBB-6DDD45312C76}, Volume = {308}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1109886}} @article{Bhardwaj:2006, Abstract = {Stem cells generate neurons in discrete regions in the postnatal mammalian brain. However, the extent of neurogenesis in the adult human brain has been difficult to establish. We have taken advantage of the integration of (14)C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral neocortex. Together with the analysis of the neocortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that, whereas nonneuronal cells turn over, neurons in the human cerebral neocortex are not generated in adulthood at detectable levels but are generated perinatally.}, Author = {Bhardwaj, Ratan D. and Curtis, Maurice A. and Spalding, Kirsty L. and Buchholz, Bruce A. and Fink, David and Bj{\"o}rk-Eriksson, Thomas and Nordborg, Claes and Gage, Fred H. and Druid, Henrik and Eriksson, Peter S. and Fris{\'e}n, Jonas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Atmosphere;research support, n.i.h., extramural ;Animals;Humans;Aging;Middle Aged;Neocortex;research support, u.s. gov't, non-p.h.s. ;Time Factors;Antimetabolites;Nuclear Warfare;01 Adult neurogenesis general;Aged;research support, non-u.s. gov't ;Autopsy;Carbon Radioisotopes;Aged, 80 and over;24 Pubmed search results 2008;Stem Cells;Bromodeoxyuridine}, Month = {8}, Nlm_Id = {7505876}, Number = {33}, Organization = {Department of Cell and Molecular Biology, Medical Nobel Institute, and Department of Forensic Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden.}, Pages = {12564-8}, Pii = {0605177103}, Pubmed = {16901981}, Title = {Neocortical neurogenesis in humans is restricted to development}, Uuid = {B51E2E31-1D41-4E60-8507-3B68643AB616}, Volume = {103}, Year = {2006}, url = {papers/Bhardwaj_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0605177103}} @article{Bi:1995, Abstract = {Vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS) when intranasally applied. We have examined cellular inflammatory changes in the CNS following VSV infection. As early as 1 day postinfection (p.i.), astrocytes were activated in the olfactory bulb (OB). This was followed by activation of microglia, first observed in the OB at day 3 p.i. Expression of inducible nitric oxide synthase was observed in activated microglia in the OB at day 3 p.i., and increased inducible nitric oxide synthase expression coincided with decreased virus titers in tissue homogenates. Expression of major histocompatibility complex (MHC) class I molecules on astrocytes and microglial, endothelial, and ependymal cells was also rapidly induced and followed by induced expression of MHC class II molecules on astrocytes and microglial and endothelial cells. Consistent with the pattern of viral dissemination, MHC molecules were expressed temporally from the rostral-to-caudal direction. Infiltration of CD8+ cells was observed as early as 1 day p.i. in the OB. CD4+ cells were detected in the OB at day 4 p.i. Increasing T-cell infiltration coincided with decreased virus titers. In contrast, B-cell infiltration of the CNS was not detected until day 14 p.i., after the virus was cleared and mice were showing behavioral signs of recovery. Breakdown of the blood-brain barrier was detected beginning at day 6 p.i., was most severe at day 8 p.i., and was followed by full recovery. Collectively, these data show that both innate immunity (production of nitric oxide) and acquired immunity (expression of MHC molecules and T-cell infiltration) are activated following VSV infection in the CNS.}, Author = {Bi, Z. and Barna, M. and Komatsu, T. and Reiss, C. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Histocompatibility Antigens Class I;T-Lymphocytes;Mice, Inbred BALB C;Animals;Astrocytes;Central Nervous System Diseases;Major Histocompatibility Complex;Nitric Oxide Synthase;Vesicular stomatitis-Indiana virus;Microglia;15 Retrovirus mechanism;Rhabdoviridae Infections;11 Glia;Time Factors;Blood-Brain Barrier;Male;Research Support, U.S. Gov't, P.H.S.;Mice;CD4-Positive T-Lymphocytes;24 Pubmed search results 2008;Immunity, Natural;Inflammation;Immunity;Amino Acid Oxidoreductases;Histocompatibility Antigens Class II}, Medline = {95395984}, Month = {10}, Nlm_Id = {0113724}, Number = {10}, Organization = {Department of Biology, New York University, New York 10003-6688, USA.}, Pages = {6466-72}, Pubmed = {7545248}, Title = {Vesicular stomatitis virus infection of the central nervous system activates both innate and acquired immunity}, Uuid = {F1DFFA9D-9A53-4360-90B0-870B109AB77B}, Volume = {69}, Year = {1995}} @article{Bianco:2001, Abstract = {The concept of producing 'spare parts'of the body for replacement of damaged or lost organs lies at the core of the varied biotechnological practices referred to generally as tissue engineering. Use of postnatal stem cells has the potential to significantly alter the perspective of tissue engineering. Successful long-term restoration of continuously self-renewing tissues such as skin, for example, depends on the use of extensively self-renewing stem cells. The identification and isolation of stem cells from a number of tissues provides appropriate targets for prospective gene therapies. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Bianco, P. and Robey, P. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Nature}, Keywords = {F abstr;Bone and Bones/cytology;10 Development;Human;Regeneration;*Stem Cells;*Tissue Engineering/trends;Animals;Support, Non-U.S. Gov't;Skin/cytology;Bone Regeneration}, Number = {6859}, Organization = {Dipartimento di Medicina Sperimentale e Patologia, Universita 'La Sapienza', Viale Regina Elena 324, Roma 00161, Italy. p.bianco\@flashnet.it}, Pages = {118-21}, Pubmed = {11689957}, Title = {Stem cells in tissue engineering}, Uuid = {0486320D-DE95-4C70-8449-6DA7BCB3841D}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689957}} @article{Biebl:2000, Abstract = {The adult central nervous system was thought to be very limited in its regenerative potential; however, the discovery that stem cell populations produce neurons in the adult brain highlights the dynamics of a previously assumed 'static'organ. The continuous generation of new neurons in the adult brain, nevertheless, leads to the question of whether neurogenesis is counterbalanced by an accompanying cell death in the same regions. The objective of this study was to stereologically analyze neurogenesis and programmed cell death in adult brain regions with known neurogenic activity. Using bromodeoxyuridine (BrdU) to identify newborn cells we find that within a few days of BrdU-labeling the adult dentate gyrus and olfactory bulb generate high numbers of newborn neurons. More importantly, dUTP-nick end labeling (TUNEL) reveals that areas of adult neurogenesis also contain high numbers of apoptotic cells. We conclude that programmed cell death may have an important regulatory function by eliminating supernumerous cells from neurogenic regions and may thus contribute to a self-renewal mechanism in the adult mammalian brain.}, Author = {Biebl, M. and Cooper, C. M. and Winkler, J. and Kuhn, H. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neurosci Lett}, Keywords = {Neurons/*cytology/metabolism;Rats;Apoptosis/*physiology;Olfactory Bulb/cytology/metabolism;Female;Cell Count;02 Adult neurogenesis migration;Animal;Rats, Wistar;Brain/*cytology/*physiology;Nerve Regeneration;Support, Non-U.S. Gov't;B;In Situ Nick-End Labeling;Dentate Gyrus/cytology/metabolism;Cell Differentiation/physiology;Bromodeoxyuridine;DNA Fragmentation}, Number = {1}, Organization = {Department of Neurology, University of Regensburg, Universitatsstrasse 84, D-93053, Regensburg, Germany.}, Pages = {17-20.}, Title = {Analysis of neurogenesis and programmed cell death reveals a self- renewing capacity in the adult rat brain}, Uuid = {29F4B02E-62A0-4228-B6A6-75247B32D5A7}, Volume = {291}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10962143}} @article{Bielas:2007, Abstract = {The axonal shafts of neurons contain bundled microtubules, whereas extending growth cones contain unbundled microtubule filaments, suggesting that localized activation of microtubule-associated proteins (MAP) at the transition zone may bundle these filaments during axonal growth. Dephosphorylation is thought to lead to MAP activation, but specific molecular pathways have remained elusive. We find that Spinophilin, a Protein-phosphatase 1 (PP1) targeting protein, is responsible for the dephosphorylation of the MAP Doublecortin (Dcx) Ser 297 selectively at the "wrist" of growing axons, leading to activation. Loss of activity at the "wrist" is evident as an impaired microtubule cytoskeleton along the shaft. These findings suggest that spatially restricted adaptor-specific MAP reactivation through dephosphorylation is important in organization of the neuronal cytoskeleton.}, Author = {Bielas, Stephanie L. and Serneo, Finley F. and Chechlacz, Magdalena and Deerinck, Thomas J. and Perkins, Guy A. and Allen, Patrick B. and Ellisman, Mark H. and Gleeson, Joseph G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Microtubule-Associated Proteins;Magnetic Resonance Imaging;Animals;Cells, Cultured;Humans;Serine;Microfilament Proteins;Phosphoprotein Phosphatases;Phosphorylation;Axons;Neurites;Hippocampus;research support, non-u.s. gov't;Male;Neuropeptides;Microtubules;Mice, Inbred Strains;Mice, Knockout;Neurons;research support, n.i.h., extramural;Mice;Cyclin-Dependent Kinase 5;24 Pubmed search results 2008;Actins;Corpus Callosum;Nerve Tissue Proteins}, Month = {5}, Nlm_Id = {0413066}, Number = {3}, Organization = {Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.}, Pages = {579-91}, Pii = {S0092-8674(07)00389-3}, Pubmed = {17482550}, Title = {Spinophilin facilitates dephosphorylation of doublecortin by PP1 to mediate microtubule bundling at the axonal wrist}, Uuid = {E5ECF94A-43EE-4C7F-B2AA-042156B9CBF9}, Volume = {129}, Year = {2007}, url = {papers/Bielas_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2007.03.023}} @article{Bielle:2005, Abstract = {Cajal-Retzius cells are critical in cortical lamination, but very little is known about their origin and development. The homeodomain transcription factor Dbx1 is expressed in restricted progenitor domains of the developing pallium: the ventral pallium (VP) and the septum. Using genetic tracing and ablation experiments in mice, we show that two subpopulations of Reelin(+) Cajal-Retzius cells are generated from Dbx1-expressing progenitors. VP- and septum-derived Reelin(+) neurons differ in their onset of appearance, migration routes, destination and expression of molecular markers. Together with reported data supporting the generation of Reelin(+) cells in the cortical hem, our results show that Cajal-Retzius cells are generated at least at three focal sites at the borders of the developing pallium and are redistributed by tangential migration. Our data also strongly suggest that distinct Cajal-Retzius subtypes exist and that their presence in different territories of the developing cortex might contribute to region-specific properties.}, Author = {Bielle, Franck and Griveau, Am{\'e}lie and Narboux-N\^{e}me, Nicolas and Vigneau, S{\'e}bastien and Sigrist, Markus and Arber, Silvia and Wassef, Marion and Pierani, Alessandra}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {10 Development;Tissue Distribution;Animals;Aging;Homeodomain Proteins;Cell Movement;Telencephalon;Cell Adhesion Molecules, Neuronal;Serine Endopeptidases;Recombinant Fusion Proteins;Calcium-Binding Protein, Vitamin D-Dependent;Mice, Neurologic Mutants;Embryo;research support, non-u.s. gov't ;Extracellular Matrix Proteins;Animals, Newborn;tau Proteins;Cerebral Cortex;Neurons;Mice;Cell Division;24 Pubmed search results 2008;Nerve Tissue Proteins;Genetic Techniques;12 Interneuron development}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Centre National de la Recherche Scientifique-Unit{\'e} Mixte de Recherche 8542, Ecole Normale Sup{\'e}rieure, 46 rue d'Ulm, 75005 Paris, France.}, Pages = {1002-12}, Pii = {nn1511}, Pubmed = {16041369}, Title = {Multiple origins of Cajal-Retzius cells at the borders of the developing pallium}, Uuid = {64967ECB-EFDA-4749-95F6-E0C57769C71A}, Volume = {8}, Year = {2005}, url = {papers/Bielle_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1511}} @article{Bierhuizen:1997, Abstract = {The further improvement of gene transfer into hematopoietic stem cells and their direct progeny will be greatly facilitated by markers that allow rapid detection and efficient selection of successfully transduced cells. For this purpose, a retroviral vector was designed and tested encoding a recombinant version of the Aequorea victoria green fluorescent protein that is enhanced for high-level expression in mammalian cells (EGFP). Murine cell lines (NIH 3T3, Rat2) and bone marrow cells transduced with this retroviral vector demonstrated a stable green fluorescence signal readily detectable by flow cytometry. Functional analysis of the retrovirally transduced bone marrow cells showed EGFP expression in in vitro clonogenic progenitors (GM-CFU), day 13 colony-forming unit-spleen (CFU-S), and in peripheral blood cells and marrow repopulating cells of transplanted mice. In conjunction with fluorescence-activated cell sorting (FACS) techniques EGFP expression could be used as a marker to select for greater than 95\%pure populations of transduced cells and to phenotypically define the transduced cells using antibodies directed against specific cell-surface antigens. Detrimental effects of EGFP expression were not observed: fluorescence intensity appeared to be stable and hematopoietic cell growth was not impaired. The data show the feasibility of using EGFP as a convenient and rapid reporter to monitor retroviral-mediated gene transfer and expression in hematopoietic cells, to select for the genetically modified cells, and to track these cells and their progeny both in vitro and in vivo.}, Author = {Bierhuizen, M. F. and Westerman, Y. and Visser, T. P. and Dimjati, W. and Wognum, A. W. and Wagemaker, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Gene Transfer Techniques;Flow Cytometry;Luminescent Proteins;Research Support, Non-U.S. Gov't;Hematopoietic Stem Cells;Female;Bone Marrow Cells;Retroviridae;Biological Markers;11 Glia;Green Fluorescent Proteins;Humans;Animals;Mice;Cells, Cultured;Genetic Vectors}, Medline = {98008093}, Month = {11}, Nlm_Id = {7603509}, Number = {9}, Organization = {Institute of Hematology, Erasmus University Rotterdam, Rotterdam, The Netherlands.}, Pages = {3304-15}, Pubmed = {9345012}, Title = {Enhanced green fluorescent protein as selectable marker of retroviral-mediated gene transfer in immature hematopoietic bone marrow cells}, Uuid = {CA937BC1-4D60-4482-80EB-4608E094687F}, Volume = {90}, Year = {1997}} @article{Bierhuizen:1999, Abstract = {The feasibility of using the enhanced green fluorescent protein (EGFP) as a selectable reporter molecule of retroviral-mediated gene transfer in immature rhesus monkey and human CD34+ hematopoietic cells was examined. Retroviral transduction with the MFG-EGFP retroviral vector resulted in readily detectable EGFP expression in 27\%of human and 11-35\%of rhesus monkey bone marrow cells, and in 17-38\%of rhesus monkey peripheral blood cells mobilized with FLT3 ligand (FL) and granulocyte colony-stimulating factor (G-CSF). In addition, we used the human CD34+ KG1A cell line as a model to study viability and growth of successfully transduced cells. Cultures of mock- and EGFP-transduced KG1A cells generated equal viable cell numbers for at least 1 month, indicating the absence of a cytotoxic effect of EGFP expression in these cells. FACS selection on the basis of EGFP and CD34 expression resulted in enriched subsets (>or = 87\%) of CD34+ EGFP-negative and CD34+ EGFP-positive KG1A, rhesus monkey and human bone marrow cells, demonstrating the potential of obtaining almost pure populations of transduced immature hematopoietic cells. EGFP expression was also readily demonstrated in erythroid and granulocyte/macrophage colonies derived from the CD34+ EGFP-positive rhesus monkey and human bone marrow cells by either inverted fluorescence microscopy or flow cytometry. Using four-color flow cytometry, EGFP expression could also be demonstrated in viable and phenotypically defined immature subpopulations of the CD34+ cells, ie those expressing little or no HLA-DR (rhesus monkey) or CD38 (human) antigens at the cell surface. These results demonstrate that EGFP is a very useful marker to monitor gene transfer efficiency in phenotypically defined immature rhesus monkey and human hematopoietic cell types and to select for these cells by multicolor flow cytometry prior to transplantation.}, Author = {Bierhuizen, M. F. and Westerman, Y. and Hartong, S. C. and Visser, T. P. and Wognum, A. W. and Wagemaker, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0887-6924}, Journal = {Leukemia}, Keywords = {Hematopoietic Stem Cell Mobilization;Colony-Forming Units Assay;Humans;Animals;Cell Separation;Transfection;Feasibility Studies;Antigens, CD34;Retroviridae;Immunophenotyping;11 Glia;Genetic Vectors;Green Fluorescent Proteins;Cell Line;Macaca mulatta;Cell Lineage;Male;Bone Marrow Cells;Recombinant Fusion Proteins;Flow Cytometry;Hematopoietic Stem Cells;Luminescent Proteins;Genes, Reporter;Biological Markers;Gene Expression;Membrane Proteins;Research Support, Non-U.S. Gov't}, Medline = {99229682}, Month = {4}, Nlm_Id = {8704895}, Number = {4}, Organization = {Institute of Hematology, Erasmus University Rotterdam, The Netherlands.}, Pages = {605-13}, Pubmed = {10214869}, Title = {Efficient detection and selection of immature rhesus monkey and human CD34+ hematopoietic cells expressing the enhanced green fluorescent protein (EGFP)}, Uuid = {1A2DDCF9-39D7-48DB-93BB-39E0AF99AAD4}, Volume = {13}, Year = {1999}} @article{Biffi:2004, Abstract = {Gene-based delivery can establish a sustained supply of therapeutic proteins within the nervous system. For diseases characterized by extensive CNS and peripheral nervous system (PNS) involvement, widespread distribution of the exogenous gene may be required, a challenge to in vivo gene transfer strategies. Here, using lentiviral vectors (LVs), we efficiently transduced hematopoietic stem cells (HSCs) ex vivo and evaluated the potential of their progeny to target therapeutic genes to the CNS and PNS of transplanted mice and correct a neurodegenerative disorder, metachromatic leukodystrophy (MLD). We proved extensive repopulation of CNS microglia and PNS endoneurial macrophages by transgene-expressing cells. Intriguingly, recruitment of these HSC-derived cells was faster and more robust in MLD mice. By transplanting HSCs transduced with the arylsulfatase A gene, we fully reconstituted enzyme activity in the hematopoietic system of MLD mice and prevented the development of motor conduction impairment, learning and coordination deficits, and neuropathological abnormalities typical of the disease. Remarkably, ex vivo gene therapy had a significantly higher therapeutic impact than WT HSC transplantation, indicating a critical role for enzyme overexpression in the HSC progeny. These results indicate that transplantation of LV-transduced autologous HSCs represents a potentially efficacious therapeutic strategy for MLD and possibly other neurodegenerative disorders.}, Author = {Biffi, Alessandra and De Palma, Michele and Quattrini, Angelo and Del Carro, Ubaldo and Amadio, Stefano and Visigalli, Ilaria and Sessa, Maria and Fasano, Stefania and Brambilla, Riccardo and Marchesini, Sergio and Bordignon, Claudio and Naldini, Luigi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0021-9738}, Journal = {J Clin Invest}, Keywords = {Mice;Cell Differentiation;Research Support, Non-U.S. Gov't;Lentivirus;Mice, Inbred C57BL;11 Glia;Motor Activity;Gene Therapy;Hematopoietic Stem Cell Transplantation;Animals;Nervous System;Cell Movement;Leukodystrophy, Metachromatic;Disease Models, Animal}, Month = {4}, Nlm_Id = {7802877}, Number = {8}, Organization = {San Raffaele Telethon Institute for Gene Therapy, San Raffaele Scienctific Institute, Milan, Italy.}, Pages = {1118-29}, Pubmed = {15085191}, Title = {Correction of metachromatic leukodystrophy in the mouse model by transplantation of genetically modified hematopoietic stem cells}, Uuid = {366E2A0F-8DB0-4F47-972C-6DCE833EF2F1}, Volume = {113}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1172/JCI200419205}} @article{Binder:1999, Abstract = {Recent work suggests that limiting the activation of the trkB subtype of neurotrophin receptor inhibits epileptogenesis, but whether or where neurotrophin receptor activation occurs during epileptogenesis is unclear. Because the activation of trk receptors involves the phosphorylation of specific tyrosine residues, the availability of antibodies that selectively recognize the phosphorylated form of trk receptors permits a histochemical assessment of trk receptor activation. In this study the anatomy and time course of trk receptor activation during epileptogenesis were assessed with immunohistochemistry, using a phospho-specific trk antibody. In contrast to the low level of phosphotrk immunoreactivity constitutively expressed in the hippocampus of adult rats, a striking induction of phosphotrk immunoreactivity was evident in the distribution of the mossy fibers after partial kindling or kainate-induced seizures. The anatomic distribution, time course, and threshold for seizure-induced phosphotrk immunoreactivity correspond to the demonstrated pattern of regulation of BDNF expression by seizure activity. These results provide immunohistochemical evidence that trk receptors undergo activation during epileptogenesis and suggest that the mossy fiber pathway is particularly important in the pro-epileptogenic effects of the neurotrophins.}, Author = {Binder, D. K. and Routbort, M. J. and McNamara, J. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Electric Stimulation;Receptor Protein-Tyrosine Kinases/*metabolism;Rats, Sprague-Dawley;07 Excitotoxicity Apoptosis;Neural Pathways/metabolism;Kainic Acid/toxicity;Rats;Immunohistochemistry;E-8;Kindling (Neurology);Animal;Support, U.S. Gov't, P.H.S.;Status Epilepticus/chemically induced/metabolism;Mossy Fibers, Hippocampal/*metabolism;Cells, Cultured;Male;Seizures/*metabolism}, Number = {11}, Organization = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.}, Pages = {4616-26.}, Title = {Immunohistochemical evidence of seizure-induced activation of trk receptors in the mossy fiber pathway of adult rat hippocampus}, Uuid = {CD93E490-14EE-4A5E-856C-18D1B8CCB404}, Volume = {19}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10341259%20http://www.jneurosci.org/cgi/content/full/19/11/4616}} @article{Binzegger:2004, Abstract = {We developed a quantitative description of the circuits formed in cat area 17 by estimating the "weight" of the projections between different neuronal types. To achieve this, we made three-dimensional reconstructions of 39 single neurons and thalamic afferents labeled with horseradish peroxidase during intracellular recordings in vivo. These neurons served as representatives of the different types and provided the morphometrical data about the laminar distribution of the dendritic trees and synaptic boutons and the number of synapses formed by a given type of neuron. Extensive searches of the literature provided the estimates of numbers of the different neuronal types and their distribution across the cortical layers. Applying the simplification that synapses between different cell types are made in proportion to the boutons and dendrites that those cell types contribute to the neuropil in a given layer, we were able to estimate the probable source and number of synapses made between neurons in the six layers. The predicted synaptic maps were quantitatively close to the estimates derived from the experimental electron microscopic studies for the case of the main sources of excitatory and inhibitory input to the spiny stellate cells, which form a major target of layer 4 afferents. The map of the whole cortical circuit shows that there are very few "strong" but many "weak" excitatory projections, each of which may involve only a few percentage of the total complement of excitatory synapses of a single neuron.}, Author = {Binzegger, Tom and Douglas, Rodney J. and Martin, Kevan A. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Presynaptic Terminals;Animals;Synapses;Thalamic Nuclei;Neural Pathways;Afferent Pathways;Imaging, Three-Dimensional;Cell Count;Axons;Pyramidal Cells;research support, non-u.s. gov't;Dendrites;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Visual Cortex;Cats;Models, Neurological;Brain Mapping}, Month = {9}, Nlm_Id = {8102140}, Number = {39}, Organization = {Institute of Neuroinformatics, University of Z{\"u}rich, and Eidgen{\"o}ssische Technische Hochschule Z{\"u}rich, CH-8057 Z{\"u}rich, Switzerland. tom.binzegger\@ncl.ac.uk}, Pages = {8441-53}, Pii = {24/39/8441}, Pubmed = {15456817}, Title = {A quantitative map of the circuit of cat primary visual cortex}, Uuid = {850C41FA-F384-4AE7-9484-DCAC3003EAED}, Volume = {24}, Year = {2004}, url = {papers/Binzegger_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1400-04.2004}} @article{Birmingham:2006, Abstract = {Off-target gene silencing can present a notable challenge in the interpretation of data from large-scale RNA interference (RNAi) screens. We performed a detailed analysis of off-targeted genes identified by expression profiling of human cells transfected with small interfering RNA (siRNA). Contrary to common assumption, analysis of the subsequent off-target gene database showed that overall identity makes little or no contribution to determining whether the expression of a particular gene will be affected by a given siRNA, except for near-perfect matches. Instead, off-targeting is associated with the presence of one or more perfect 3' untranslated region (UTR) matches with the hexamer or heptamer seed region (positions 2-7 or 2-8) of the antisense strand of the siRNA. These findings have strong implications for future siRNA design and the application of RNAi in high-throughput screening and therapeutic development.}, Author = {Birmingham, Amanda and Anderson, Emily M. and Reynolds, Angela and Ilsley-Tyree, Diane and Leake, Devin and Fedorov, Yuriy and Baskerville, Scott and Maksimova, Elena and Robinson, Kathryn and Karpilow, Jon and Marshall, William S. and Khvorova, Anastasia}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {Cell Survival;Base Pairing;Humans;Transfection;Oligonucleotide Array Sequence Analysis;Databases, Factual;Base Pair Mismatch;Sensitivity and Specificity;Sequence Alignment;23 Technique;Computational Biology;Silicon;Gene Expression Profiling;Hela Cells;RNA, Small Interfering;RNA, Messenger;Cell Line;Numerical Analysis, Computer-Assisted;21 Neurophysiology;Gene Silencing;23 RNAi;24 Pubmed search results 2008;3' Untranslated Regions}, Month = {3}, Nlm_Id = {101215604}, Number = {3}, Organization = {Dharmacon Research, 2650 Crescent Drive, \#100, Lafayette, Colorado 80026, USA.}, Pages = {199-204}, Pii = {nmeth854}, Pubmed = {16489337}, Title = {3' UTR seed matches, but not overall identity, are associated with RNAi off-targets}, Uuid = {FEC9A130-48A4-11DB-A317-000D9346EC2A}, Volume = {3}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth854}} @article{Bishop:2002, Abstract = {The mammalian neocortex is organized into subdivisions referred to as areas that are distinguished from one another by differences in architecture, axonal connections, and function. The transcription factors EMX1, EMX2, and PAX6 have been proposed to regulate arealization. Emx1 and Emx2 are expressed by progenitor cells in a low rostrolateral to high caudomedial gradient across the embryonic neocortex, and Pax6 is expressed in a high rostrolateral to low caudomedial gradient. Recent evidence has suggested that EMX2 and PAX6 have a role in the genetic regulation of arealization. Here we use a panel of seven genes (Cad6, Cad8, Id2, RZRbeta, p75, EphA7, and ephrin-A5) representative of a broad range of proteins as complementary markers of positional identity to obtain a more thorough assessment of the suggested roles for EMX2 and PAX6 in arealization, and in addition to assess the proposed but untested role for EMX1 in arealization. Orderly changes in the size and positioning of domains of marker expression in Emx2 and Pax6 mutants strongly imply that rostrolateral areas (motor and somatosensory) are expanded, whereas caudomedial areas (visual) are reduced in Emx2 mutants and that opposite effects occur in Pax6 mutants, consistent with their opposing gradients of expression. In contrast, patterns of marker expression, as well as the distribution of area-specific thalamocortical projections, appear normal in Emx1 mutants, indicating that they do not exhibit changes in arealization. This lack of a defined role for EMX1 in arealization is supported by our finding of similar shifts in patterns of marker expression in Emx1; Emx2 double mutants as in Emx2 mutants. Thus, our findings indicate that EMX2 and PAX6 regulate, in opposing manners, arealization of the neocortex and impart positional identity to cortical cells, whereas EMX1 appears not to have a role in this process. 1529-2401 Journal Article}, Author = {Bishop, K. M. and Rubenstein, J. L. and O'Leary, D. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {10 Development;Neocortex/anatomy &histology/*embryology/*metabolism;Cadherins/genetics/metabolism;Receptors, Cell Surface/genetics/metabolism;Animals;Mice, Mutant Strains;Repressor Proteins/metabolism;Ephrin-A5;*Gene Expression Regulation, Developmental;Homeodomain Proteins/genetics/*metabolism;DNA-Binding Proteins/genetics/metabolism;F pdf;Receptors, Melatonin;In Situ Hybridization;Animals, Newborn;Support, Non-U.S. Gov't;Morphogenesis;Trans-Activators/genetics/metabolism;Support, U.S. Gov't, P.H.S.;Transcription Factors/genetics/metabolism;Receptors, Cytoplasmic and Nuclear/genetics/metabolism;Mice;RNA, Messenger/metabolism;Membrane Proteins/genetics/metabolism;Eye Proteins/metabolism}, Number = {17}, Organization = {Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {7627-38}, Pubmed = {12196586}, Title = {Distinct actions of Emx1, Emx2, and Pax6 in regulating the specification of areas in the developing neocortex}, Uuid = {FFDFD207-7BA6-4E68-A251-CD5B065C839F}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12196586}} @article{Bittman:1999, Abstract = {Proliferating cells of the developing murine neocortex couple together into clusters during neurogenesis. Previously, we have shown that these clusters contain neural precursors in all phases of the cell cycle except M phase, and that they extend a nestin-expressing process from the cluster to the pial surface. In addition, coupling within neocortical cell clusters is a dynamic process related to the cell cycle, with maximal coupling in S/G2 phase, uncoupling in M phase and then recoupling during G1 and S phases of the cell cycle. In the present study, we use immunohistochemistry to demonstrate that cycling neocortical cells as well as radial glial cells express the gap junction proteins connexin 26 and connexin 43. Furthermore, we demonstrate that biocytin labeled clusters extend processes to the pial surface that express the glial cell antigen RC2. Lastly, by combining bromodeoxyuridine and connexin immunohistochemistry on acutely dissociated neocortical cells, we show that the percentage of cycling cells immunoreactive to connexin 26 and connexin 43 changes through the cell cycle. These results indicate that radial glial cells as well as neural precursors couple into clusters, and suggest that through differential regulation of connexins, neocortical precursors may compartmentalize as they progress through the cell cycle.}, Author = {Bittman, K. S. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cereb Cortex}, Keywords = {Nerve Tissue Proteins/*physiology;10 Development;Fetal Development/physiology;Neocortex/cytology/*embryology;Comparative Study;Cell Cycle/physiology;Stem Cells/physiology;Animal;Connexin 43/*physiology;Mice, Inbred Strains;Antibody Specificity;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Mice;Cell Differentiation/physiology;F;Nerve Fibers/physiology;Connexins/*physiology}, Number = {2}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs 06268-4156, USA.}, Pages = {188-95.}, Title = {Differential regulation of connexin 26 and 43 in murine neocortical precursors}, Uuid = {A7512708-70B1-479A-9858-8FDBEC96F031}, Volume = {9}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10220231}} @article{Bittman:2002, Abstract = {Intercellular communication through gap junction channels is a prominent feature of the developing cerebral cortex. In the first 2 weeks after birth, a time critical in the development of the rat neocortex, extensive cell coupling has been documented that diminishes as the cortex matures. Among the family of gap junction proteins, connexins 26, 36, and 43 are differentially expressed during cortical development. We used intracellular dye injections and connexin immunohistochemistry to investigate the coupling patterns and connexin expression between the different neuronal and glial cell types of the developing cortex of the rat. We found that neurons and glia couple homotypically and heterotypically at postnatal days 7 and 14. Although the prevalence of coupling was homotypic, there was considerable heterotypic coupling that involved pyramidal and nonpyramidal neurons, the principal neuronal cell types of the cortex, or neurons and astrocytes. Coupling between different cell types appeared to be mediated by differential expression of connexins 26, 36, and 43. It may be that coupling between cells in the developing neocortex is a function of the spatial and temporal expression of these and other connexin proteins.}, Author = {Bittman, Kevin and Becker, David L. and Cicirata, Federico and Parnavelas, John G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Fluorescent Dyes;Connexin 43;Animals;Astrocytes;Gene Expression Regulation, Developmental;Rats;Microscopy, Confocal;Cell Communication;Rats, Sprague-Dawley;Axons;Fluorescein-5-isothiocyanate;Pyramidal Cells;Gap Junctions;Connexins;Dendrites;research support, non-u.s. gov't ;Cerebral Cortex;21 Neurophysiology;Cell Size;Neuroglia;Neurons;Interneurons;24 Pubmed search results 2008;Immunohistochemistry;Biotin}, Month = {2}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.}, Pages = {201-12}, Pii = {10.1002/cne.2121}, Pubmed = {11807831}, Title = {Connexin expression in homotypic and heterotypic cell coupling in the developing cerebral cortex}, Uuid = {8CD735F3-2C00-4449-BC3D-F40F4B43C949}, Volume = {443}, Year = {2002}, url = {papers/Bittman_JCompNeurol2002.pdf}} @article{Bittman:1997, Abstract = {Cells within the ventricular zone (VZ) of developing neocortex are coupled together into clusters by gap junction channels. The specific role of clustering in cortical neurogenesis is unknown; however, clustering provides a means for spatially restricted local interactions between subsets of precursors and other cells within the VZ. In the present study, we have used a combination of 5-bromo-2'-deoxyuridine (BrDU) pulse labeling, intracellular biocytin labeling, and immunocytochemistry to determine when in the cell cycle VZ cells couple and uncouple from clusters and to determine what cell types within the VZ are coupled to clusters. Our results indicate that clusters contain radial glia and neural precursors but do not contain differentiating or migrating neurons. In early neurogenesis, all precursors in S and G2 phases of the cell cycle are coupled, and approximately half of the cells in G1 are coupled. In late neurogenesis, however, over half of the cells in both G1 and S phases are not coupled to VZ clusters, whereas all cells in G2 are coupled to clusters. Increased uncoupling in S phase during late neurogenesis may contribute to the greater percentage of VZ cells exiting the cell cycle at this time. Consistent with this hypothesis, we found that pharmacologically uncoupling VZ cells with octanol decreases the percentage of VZ cells that enter S phase. These results demonstrate that cell clustering in the VZ is restricted to neural precursors and radial glia, is dynamic through the cell cycle, and may play a role in regulating neurogenesis.}, Author = {Bittman, K. and Owens, D. F. and Kriegstein, A. R. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Pregnancy;Animals;Lysine;Epithelial Cells;Tubulin;Cell Cycle;Female;Cell Communication;Gap Junctions;G2 Phase;Cerebral Ventricles;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;Mice;G1 Phase;Bromodeoxyuridine;24 Pubmed search results 2008;S Phase;Research Support, Non-U.S. Gov't}, Medline = {97426553}, Month = {9}, Nlm_Id = {8102140}, Number = {18}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269-4156, USA.}, Pages = {7037-44}, Pubmed = {9278539}, Title = {Cell coupling and uncoupling in the ventricular zone of developing neocortex}, Uuid = {2F0119C9-3FFA-4514-96A1-838632FCFA8B}, Volume = {17}, Year = {1997}} @article{Bjarnason:2001, Abstract = {We studied the relative RNA expression of clock genes throughout one 24-hour period in biopsies obtained from the oral mucosa and skin from eight healthy diurnally active male study participants. We found that the human clock genes hClock, hTim, hPer1, hCry1, and hBmal1 are expressed in oral mucosa and skin, with a circadian profile consistent with that found in the suprachiasmatic nuclei and the peripheral tissues of rodents. hPer1, hCry1, and hBmal1 have a rhythmic expression, peaking early in the morning, in late afternoon, and at night, respectively, whereas hClock and hTim are not rhythmic. This is the first human study to show a circadian profile of expression for all five clock genes as documented in rodents, suggesting their functional importance in man. In concurrent oral mucosa biopsies, thymidylate synthase enzyme activity, a marker for DNA synthesis, had a circadian variation with peak activity in early afternoon, coinciding with the timing of S phase in our previous study on cell-cycle timing in human oral mucosa. The major peak in hPer1 expression occurs at the same time of day as the peak in G(1) phase in oral mucosa, suggesting a possible link between the circadian clock and the mammalian cell cycle. 0002-9440 Clinical Trial Journal Article}, Author = {Bjarnason, G. A. and Jordan, R. C. and Wood, P. A. and Li, Q. and Lincoln, D. W. and Sothern, R. B. and Hrushesky, W. J. and Ben-David, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Am J Pathol}, Keywords = {F abstr;10 Development;Cell Cycle/physiology;Trans-Activators/*genetics;Mouth Mucosa/enzymology/*metabolism;Gene Expression Regulation;Circadian Rhythm/genetics/*physiology;Thymidylate Synthase/genetics/metabolism;Support, U.S. Gov't, Non-P.H.S.;Transcription Factors/genetics;Nuclear Proteins/genetics;RNA, Messenger/genetics/metabolism;Support, Non-U.S. Gov't;Flavoproteins/genetics;Skin/*metabolism;Support, U.S. Gov't, P.H.S.}, Number = {5}, Organization = {Toronto-Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada. bjarnason\@srcl.sunnybrook.utoronto.ca}, Pages = {1793-801}, Pubmed = {11337377}, Title = {Circadian expression of clock genes in human oral mucosa and skin: association with specific cell-cycle phases}, Uuid = {C480EC4E-ED6A-4977-96D7-5D882780048B}, Volume = {158}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11337377}} @article{Bjorklund:1992, Abstract = {The ability of intrastriatal grafts of fetal mesencephalic dopamine neurons to ameliorate the symptoms of experimental and clinical parkinsonism has raised the question of the mechanisms underlying the transplant-induced functional effects. Recent studies have taken advantage of quantitative cytochemical and in situ hybridization techniques to study functional graft-host interactions at the cellular level in the rat Parkinson model. The results provide evidence that behaviorally functional grafts restore dopaminergic neurotransmission and normalize dopamine receptor function in the denervated striatum, and that these effects are likely to depend on both synaptic and extrasynaptic mechanisms. 0959-4388 Journal Article Review Review, Tutorial}, Author = {Bjorklund, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Curr Opin Neurobiol}, Keywords = {Parkinson Disease/*therapy;17 Transplant Regeneration;Human;L abstr;Dopamine/*physiology;*Brain Tissue Transplantation;Animals}, Number = {5}, Organization = {Department of Medical Research, University of Lund, Sweden.}, Pages = {683-9}, Pubmed = {1422126}, Title = {Dopaminergic transplants in experimental parkinsonism: cellular mechanisms of graft-induced functional recovery}, Uuid = {64CEAD3A-EC80-11DA-8605-000D9346EC2A}, Volume = {2}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1422126}} @article{Bjorklund:2000, Abstract = {In animal models, immature neural precursors can replace lost neurons, restore function and promote brain self-repair. Clinical trials in Parkinson's disease suggest that similar approaches may also work in the diseased human brain. But how realistic is it that cell replacement can be developed into effective clinical therapy? 1097-6256 Journal Article Review Review, Tutorial}, Author = {Bjorklund, A. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Nat Neurosci}, Keywords = {Human;Animals;Huntington Disease/therapy;Rats;Recovery of Function;Parkinson Disease/therapy;*Stem Cell Transplantation;Swine;Central Nervous System Diseases/*therapy;Cerebrovascular Accident/therapy;Epilepsy/therapy;Clinical Trials;Seizures/prevention &control;06 Adult neurogenesis injury induced;Neurons/*transplantation;Cell Transplantation/methods/*trends;Brain/*cytology/embryology;D, L pdf}, Number = {6}, Organization = {The authors are at the Wallenberg Neuroscience Center, Lund University, Solvegatan 17, S-223 62 Lund, Sweden. anders.bjorklund\@mphy.lu.se}, Pages = {537-44}, Title = {Cell replacement therapies for central nervous system disorders}, Uuid = {4E694C67-EC7F-11DA-8605-000D9346EC2A}, Volume = {3}, Year = {2000}, url = {papers/Bjorklund_NatNeurosci2000.pdf}} @article{Black:2001, Author = {Black, I. B. and Woodbury, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1079-9796}, Journal = {Blood Cells Mol Dis}, Keywords = {Neurons;Cell Differentiation;Research Support, Non-U.S. Gov't;Immunophenotyping;Rats;Bone Marrow Cells;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;review, tutorial;Humans;Animals;Stromal Cells;review}, Medline = {21375886}, Nlm_Id = {9509932}, Number = {3}, Organization = {Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, 675 Hoes Lane, CABM 342, Piscataway, NJ 08854, USA. black\@cabm.rutgers.edu}, Pages = {632-6}, Pii = {S1079979601904231}, Pubmed = {11482877}, Title = {Adult rat and human bone marrow stromal stem cells differentiate into neurons}, Uuid = {B3076514-E828-4E6F-949F-99B37396980A}, Volume = {27}, Year = {2001}, url = {papers/Black_BloodCellsMolDis2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/bcmd.2001.0423}} @article{Blackshaw:2002, Abstract = {1097-6256 Comment News}, Author = {Blackshaw, S. and Cepko, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Nat Neurosci}, Keywords = {17 Transplant Regeneration;Cell Culture/*methods;Human;Brain/cytology/growth &development;Graft Survival/physiology;Nerve Growth Factors/therapeutic use;Cell Differentiation/physiology;Stem Cell Transplantation/*methods;Brain Tissue Transplantation/*methods;L pdf;Animals;Stem Cells/*cytology/metabolism;Neurodegenerative Diseases/*therapy}, Number = {12}, Pages = {1251-2}, Title = {Stem cells that know their place}, Uuid = {BEE1CD4E-8B22-4E77-A2F2-9468F5F4236E}, Volume = {5}, Year = {2002}, url = {papers/Blackshaw_NatNeurosci2002}} @article{Blanton:1989, Abstract = {We describe methods for obtaining stable, whole-cell recordings from neurons in brain hemispheres from turtles and in brain slices from rats and turtles. Synaptic currents and membrane properties of central neurons can be studied in voltage and current clamp in cells maintained within their endogenous synaptic circuits. The methods described here are compatible with unmodified dissecting microscopes and recording chambers, and with brain slices of standard thickness (400-500 microns).}, Author = {Blanton, M. G. and Lo Turco, J. J. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci Methods}, Keywords = {Electric Stimulation;10 Development;Comparative Study;Cerebral Cortex/*physiology;Mammals/*physiology;Rats;In Vitro;Turtles/*physiology;Animal;F;Evoked Potentials;Support, U.S. Gov't, P.H.S.;Rats, Inbred Strains}, Number = {3}, Organization = {Department of Neurology, Stanford University Medical Center, CA 94305- 5300.}, Pages = {203-10.}, Title = {Whole cell recording from neurons in slices of reptilian and mammalian cerebral cortex}, Uuid = {8FDA386E-7B7B-41E7-B2B8-20720BC5041E}, Volume = {30}, Year = {1989}, url = {papers/Blanton_JNeurosciMethods1989.pdf}} @article{Blesch:2001, Abstract = {Vector systems for the regulated and reversible expression of therapeutic genes are likely to improve the safety and efficacy of gene therapy for medical disease. In the present study, we investigated whether the expression of genes transferred into the central nervous system by ex vivo gene therapy can be regulated in vivo leading to controlled neuronal survival and axonal growth. Primary rat fibroblasts were transfected with a retrovirus containing a tetracycline responsive promoter for the expression of the neurotrophin nerve growth factor (NGF) or green fluorescent protein as a control (GFP). After lesions of basal forebrain cholinergic neurons, NGF-mediated neuronal rescue and axonal growth could be completely controlled over a 2-week period by the addition or removal of the tetracycline modulator doxycycline in the animals' drinking water. Further, continued expression of the reporter gene GFP could be reliably and repeatedly turned on and off in the injured CNS for at least 3 months post-grafting, the longest time point investigated. These data constitute the first report of regulated neuronal rescue and axonal growth by controlled neurotrophin gene delivery and long-term, regulated expression using ex vivo CNS gene therapy.}, Author = {Blesch, A. and Conner, J. M. and Tuszynski, M. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Animals;Central Nervous System Diseases;Rats;Research Support, U.S. Gov't, Non-P.H.S.;Fibroblasts;Female;Axons;Polysaccharides;Retroviridae;11 Glia;Time Factors;Genetic Vectors;Spinal Cord;Analysis of Variance;Rats, Inbred F344;Research Support, U.S. Gov't, P.H.S.;Green Fluorescent Proteins;Gene Therapy;Neurons;Promoter Regions (Genetics);Anti-Bacterial Agents;Luminescent Proteins;Doxycycline;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {21318992}, Month = {6}, Nlm_Id = {9421525}, Number = {12}, Organization = {Department of Neurosciences-0626, University of California, San Diego, La Jolla, CA 92093-0626, USA.}, Pages = {954-60}, Pubmed = {11426336}, Title = {Modulation of neuronal survival and axonal growth in vivo by tetracycline-regulated neurotrophin expression}, Uuid = {8022F549-D6A8-4823-9465-A7760D1F93DA}, Volume = {8}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301480}} @article{Blitz:2005, Abstract = {Local interneurons provide feed-forward inhibition from retinal ganglion cells (RGCs) to thalamocortical (TC) neurons, but questions remain regarding the timing, magnitude, and functions of this inhibition. Here, we identify two types of inhibition that are suited to play distinctive roles. We recorded excitatory and inhibitory postsynaptic currents (EPSCs/IPSCs) in TC neurons in mouse brain slices and activated individual RGC inputs. In 34\%of TC neurons, we identified EPSCs and IPSCs with identical thresholds that were tightly correlated, indicating activation by the same RGC. Such "locked" IPSCs occurred 1 ms after EPSC onset. The remaining neurons had only "nonlocked" inhibition, in which EPSCs and IPSCs had different thresholds, indicating activation by different RGCs. Nonlocked inhibition may refine receptive fields within the LGN by providing surround inhibition. In contrast, dynamic-clamp recordings suggest that locked inhibition improves the precision of synaptically evoked responses in individual TC neurons by eliminating secondary spikes.}, Author = {Blitz, Dawn M. and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Excitatory Postsynaptic Potentials;Animals;Synapses;Neuronal Plasticity;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Patch-Clamp Techniques;Visual Pathways;Organ Culture Techniques;Visual Fields;Time Factors;Vision;Action Potentials;21 Neurophysiology;Mice;Interneurons;24 Pubmed search results 2008;Neural Inhibition;Geniculate Bodies;Retinal Ganglion Cells}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Neurobiology Department, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {917-28}, Pii = {S0896-6273(05)00071-1}, Pubmed = {15797552}, Title = {Timing and specificity of feed-forward inhibition within the LGN}, Uuid = {00047A07-83D4-4D83-868C-5C75CEF9433C}, Volume = {45}, Year = {2005}, url = {papers/Blitz_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.01.033}} @article{Bloodgood:2007, Abstract = {Recent studies have revealed that Ca(2+) signals evoked by action potentials or by synaptic activity within individual dendritic spines are regulated at multiple levels. Ca(2+) influx through glutamate receptors and voltage-sensitive Ca(2+) channels located on spines depends on the channel subunit composition, the activity of kinases and phosphatases, the local membrane potential and past patterns of activity. Furthermore, sources of spine Ca(2+) interact nonlinearly such that activation of one Ca(2+) channel can enhance or depress the activity of others. These studies have revealed that each spine is a complex and partitioned Ca(2+) signaling domain capable of autonomously regulating the electrical and biochemical consequences of synaptic activity.}, Author = {Bloodgood, and Sabatini,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9111376}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Pii = {S0959-4388(07)00057-8}, Pubmed = {17451936}, Title = {Ca(2+) signaling in dendritic spines}, Uuid = {F548687F-C1EC-4B78-B3BE-19CC8AF01A1A}, Year = {2007}, url = {papers/Bloodgood_CurrOpinNeurobiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2007.04.003}} @article{Bloodgood:2007a, Abstract = {The roles of voltage-sensitive sodium (Na) and calcium (Ca) channels located on dendrites and spines in regulating synaptic signals are largely unknown. Here we use 2-photon glutamate uncaging to stimulate individual spines while monitoring uncaging-evoked excitatory postsynaptic potentials (uEPSPs) and Ca transients. We find that, in CA1 pyramidal neurons in acute mouse hippocampal slices, CaV(2.3) voltage-sensitive Ca channels (VSCCs) are found selectively on spines and act locally to dampen uncaging-evoked Ca transients and somatic potentials. These effects are mediated by a regulatory loop that requires opening of CaV(2.3) channels, voltage-gated Na channels, small conductance Ca-activated potassium (SK) channels, and NMDA receptors. Ca influx through CaV(2.3) VSCCs selectively activates SK channels, revealing the presence of functional Ca microdomains within the spine. Our results suggest that synaptic strength can be modulated by mechanisms that regulate voltage-gated conductances within the spine but do not alter the properties or numbers of synaptic glutamate receptors.}, Author = {Bloodgood, Brenda L. and Sabatini, Bernardo L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {in vitro;Electrophysiology;Animals;Synapses;Small-Conductance Calcium-Activated Potassium Channels;Sodium Channels;Dendritic Spines;Hippocampus;Pyramidal Cells;Mice, Inbred C57BL;research support, non-u.s. gov't;Calcium;Calcium Channels, R-Type;Temperature;Protein Structure, Tertiary;21 Neurophysiology;research support, n.i.h., extramural;Mice;Cation Transport Proteins;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Ion Channel Gating;Excitatory Postsynaptic Potentials}, Month = {1}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {249-60}, Pii = {S0896-6273(06)01022-1}, Pubmed = {17224406}, Title = {Nonlinear regulation of unitary synaptic signals by CaV(2.3) voltage-sensitive calcium channels located in dendritic spines}, Uuid = {27D2740D-9B86-43C1-89EB-D43E591FA61E}, Volume = {53}, Year = {2007}, url = {papers/Bloodgood_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.12.017}} @article{Bloodgood:2005, Abstract = {In mammalian excitatory neurons, dendritic spines are separated from dendrites by thin necks. Diffusion across the neck limits the chemical and electrical isolation of each spine. We found that spine/dendrite diffusional coupling is heterogeneous and uncovered a class of diffusionally isolated spines. The barrier to diffusion posed by the neck and the number of diffusionally isolated spines is bidirectionally regulated by neuronal activity. Furthermore, coincident synaptic activation and postsynaptic action potentials rapidly restrict diffusion across the neck. The regulation of diffusional coupling provides a possible mechanism for determining the amplitude of postsynaptic potentials and the accumulation of plasticity-inducing molecules within the spine head.}, Author = {Bloodgood, Brenda L. and Sabatini, Bernardo L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Fluorescence;Animals;Synapses;Rats;Transfection;Glutamic Acid;Synaptic Transmission;Patch-Clamp Techniques;Dendritic Spines;Cytoplasm;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Receptors, AMPA;research support, non-u.s. gov't;Green Fluorescent Proteins;Organ Culture Techniques;Dendrites;Receptors, GABA-A;Action Potentials;21 Neurophysiology;Neurons;Viscosity;Diffusion;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Month = {11}, Nlm_Id = {0404511}, Number = {5749}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {866-9}, Pii = {310/5749/866}, Pubmed = {16272125}, Title = {Neuronal activity regulates diffusion across the neck of dendritic spines}, Uuid = {B54E291F-C612-4F25-9D32-6C350F0A2561}, Volume = {310}, Year = {2005}, url = {papers/Bloodgood_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1114816}} @article{Blumcke:2001, Abstract = {A considerable potential for neurogenesis has been identified in the epileptic rat hippocampus. Here, we explore this feature in human patients suffering from chronic mesial temporal lobe epilepsy. Immunohistochemical detection of the neurodevelopmental antigen nestin was used to detect neural precursor cells, and cell-type specific markers were employed to study their histogenetic origin and potential for neuronal or glial differentiation. The ontogenetic regulation of nestin-positive precursors was established in human control brains (week 19 of gestation-15 years of age). A striking increase of nestin- immunoreactive cells within the hilus and dentate gyrus could be observed in a group of young patients with temporal lobe epilepsy (TLE) and surgical treatment before age 2 years compared to adult TLE patients and controls. The cellular morphology and regional distribution closely resembled nestin-immunoreactive granule-cell progenitors transiently expressed during prenatal human hippocampus development. An increased Ki-67 proliferation index and clusters of supragranular nestin-immunoreactive cells within the molecular layer of the dentate gyrus were also noted in the group of young TLE patients. Confocal studies revealed colocalization of nestin and the betaIII isoform of tubulin, indicating a neuronal fate for some of these cells. Vimentin was consistently expressed in nestin-immunoreactive cells, whereas cell lineage-specific markers, i.e., glial fibrillary acidic protein, MAP2, neurofilament protein, NeuN, or calbindin D-28k failed to colocalize. These findings provide evidence for increased neurogenesis in pediatric patients with early onset of temporal lobe epilepsy and/or point towards a delay in hippocampal maturation in a subgroup of patients with TLE. Using Smart Source Parsing}, Author = {Blumcke, I. and Schewe, J. C. and Normann, S. and Brustle, O. and Schramm, J. and Elger, C. E. and Wiestler, O. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Hippocampus}, Keywords = {D abstr}, Number = {3}, Organization = {Department of Neuropathology, University of Bonn Medical Center, Germany.}, Pages = {311-21}, Title = {Increase of nestin-immunoreactive neural precursor cells in the dentate gyrus of pediatric patients with early-onset temporal lobe epilepsy}, Uuid = {AD8B01B1-A3E5-11DA-AB00-000D9346EC2A}, Volume = {11}, Year = {2001}} @article{Blumenthal:1987, Abstract = {We have studied fusion between membranes of vesicular stomatitis virus (VSV) and Vero cells using an assay for lipid mixing based on the relief of self-quenching of octadecylrhodamine (R18) fluorescence. We could identify the two pathways of fusion by the kinetics of R18 dequenching, effects of inhibitors, temperature dependence, and dependence on osmotic pressure. Fusion at the plasma membrane began immediately after lowering the pH below 6 and showed an approximately exponential time course, whereas fusion via the endocytic pathway (pH 7.4) became apparent after a time delay of about 2 min. Fusion via the endocytic pathway was attenuated by treating cells with metabolic inhibitors and agents that raise the pH of the endocytic vesicle. A 10-fold excess of unlabeled virus arrested R18VSV entry via the endocytic pathway, whereas R18 dequenching below pH 6 (fusion at the plasma membrane) was not affected by the presence of unlabeled virus. The temperature dependence for fusion at pH 7.4 (in the endosome) was much steeper than that for fusion at pH 5.9 (with the plasma membrane). Fusion via the endocytic pathway was attenuated at hypo-osmotic pressures, whereas fusion at the plasma membrane was not affected by this treatment. The pH profile of Vero-VSV fusion at the plasma membrane, as measured by the dequenching method, paralleled that observed for VSV-induced cell-cell fusion. Fusion was blocked by adding neutralizing antibody to the Vero-VSV complexes. Activation of the fusion process by lowering the pH was reversible, in that the rate of fusion was arrested by raising the pH back to 7.4. The observation that pH-dependent fusion occurred at similar rates with fragments and with intact cells indicates that pH, voltage, or osmotic gradients are not required for viral fusion.}, Author = {Blumenthal, R. and Bali-Puri, A. and Walter, A. and Covell, D. and Eidelman, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {Rhodamines;Cell Membrane;Spectrometry, Fluorescence;Vero Cells;Kinetics;Fluorescent Dyes;Receptors, Virus;Thermodynamics;Vesicular stomatitis-Indiana virus;15 Retrovirus mechanism;Humans;Hydrogen-Ion Concentration;Animals;24 Pubmed search results 2008}, Medline = {88007587}, Month = {10}, Nlm_Id = {2985121R}, Number = {28}, Organization = {Section of Membrane Structure and Function, National Cancer Institute, Bethesda, Maryland 20892.}, Pages = {13614-9}, Pubmed = {2820977}, Title = {pH-dependent fusion of vesicular stomatitis virus with Vero cells. Measurement by dequenching of octadecyl rhodamine fluorescence}, Uuid = {7D65D6AF-EE2C-11DA-8605-000D9346EC2A}, Volume = {262}, Year = {1987}} @article{Bock:2000, Abstract = {The human genome is rife with the proviral remains of many ancient retroviruses. The past year has seen significant progress in understanding the structure, distribution and potential function of many of these elements. Although hypotheses concerning the potential effects of these elements are common, however, incisive experiments to test any functions remain much less so.}, Author = {Bock, M. and Stoye, J. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0959-437X}, Journal = {Curr Opin Genet Dev}, Keywords = {15 ERVs retroelements;Endogenous Retroviruses;24 Pubmed search results 2008;Phylogeny;Evolution, Molecular;Genetic Code;Genome, Human;15 Retrovirus mechanism;Humans;Proviruses;Germ-Line Mutation;review;Animals}, Medline = {20541599}, Month = {12}, Nlm_Id = {9111375}, Number = {6}, Organization = {Division of Virology, National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK.}, Pages = {651-5}, Pii = {S0959437X00001386}, Pubmed = {11088016}, Title = {Endogenous retroviruses and the human germline}, Uuid = {DF06D492-3F8A-46B8-90AA-EB6FC4B1A00A}, Volume = {10}, Year = {2000}} @article{Bodick:1982, Abstract = {A previous report details morphological alterations in dendritic structure of cortical neurons in severe neurobehavioral retardation of unknown etiology. Using computer graphic techniques, the present study describes perturbations in the 3-dimensional character of the microtubular array, which correspond to degenerative change in dendritic geometry. In large proximal processes, two types of array have been reconstructed. Segmented microtubules may form a continuous helical swirl which underlies a bulge in the dendritic cylinder. Alternatively, small groups of microtubules, while maintaining orderly internal organization, may be disoriented with respect to the long axis of the process. In varicose regions of the dendrite the microtubular array is discontinuous. Microtubules course side by side through constructed regions, only to splay out and terminate within expanded regions. These pathological alterations in the microtubular array contrast sharply with the cortical dendritic microtubular array reconstructed from the normal adult mouse. Perturbation in those parameters which determine packing of microtubules within the dendritic process is also documented. In the pathological condition, microtubules lose the ability to exclude one another from close approach. The role of cross-linking molecules in maintaining the integrity of the microtubular array, and the role of microtubules in maintaining the geometry of the dendrite, are considered.}, Author = {Bodick, N. and Stevens, J. K. and Sasaki, S. and Purpura, D. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {10 Development;Golgi Apparatus;Humans;10 Structural plasticity;Female;Infant;Staining and Labeling;Get paper from library;Male;Dendrites;Microtubules;Research Support, U.S. Gov't, P.H.S.;Computers;Developmental Disabilities;Cerebral Cortex;Microscopy, Electron;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {83102363}, Month = {11}, Nlm_Id = {0045503}, Number = {3}, Pages = {299-309}, Pubmed = {6185183}, Title = {Microtubular disarray in cortical dendrites and neurobehavioral failure. II. Computer reconstruction of perturbed microtubular arrays}, Uuid = {1C1714B3-F0FA-451A-B744-3A9EC141AD3D}, Volume = {281}, Year = {1982}} @article{Boehm:1997, Abstract = {Interferons are cytokines that play a complex and central role in the resistance of mammalian hosts to pathogens. Type I interferon (IFN-alpha and IFN-beta) is secreted by virus-infected cells. Immune, type II, or gamma-interferon (IFN-gamma) is secreted by thymus-derived (T) cells under certain conditions of activation and by natural killer (NK) cells. Although originally defined as an agent with direct antiviral activity, the properties of IFN-gamma include regulation of several aspects of the immune response, stimulation of bactericidal activity of phagocytes, stimulation of antigen presentation through class I and class II major histocompatibility complex (MHC) molecules, orchestration of leukocyte-endothelium interactions, effects on cell proliferation and apoptosis, as well as the stimulation and repression of a variety of genes whose functional significance remains obscure. The implementation of such a variety of effects by a single cytokine is achieved by complex patterns of cell-specific gene regulation: Several IFN-gamma-regulated genes are themselves components of transcription factors. The IFN-gamma response is itself regulated by interaction with responses to other cytokines including IFN-alpha/beta, TNF-alpha, and IL-4. Over 200 genes are now known to be regulated by IFN-gamma and they are listed in a World Wide Web document that accompanies this review. However, much of the cellular response to IFN-gamma can be described in terms of a set of integrated molecular programs underlying well-defined physiological systems, for example the induction of efficient antigen processing for MHC-mediated antigen presentation, which play clearly defined roles in pathogen resistance. A promising approach to the complexity of the IFN-gamma response is to extend the analysis of the less understood IFN-gamma-regulated genes in terms of molecular programs functional in pathogen resistance.}, Author = {Boehm, U. and Klamp, T. and Groot, M. and Howard, J. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0732-0582}, Journal = {Annu Rev Immunol}, Keywords = {Models, Biological;Antigen Presentation;Interferon Type I;Antiviral Agents;Respiratory Burst;Gene Expression Regulation;Signal Transduction;research support, non-u.s. gov't ;14 Immune;Tumor Necrosis Factor-alpha;Apoptosis;Interferon Type II;Animals;Humans;24 Pubmed search results 2008;review;Tryptophan}, Nlm_Id = {8309206}, Organization = {Institute for Genetics, University of Cologne, K{\"o}ln, Germany. UBOEHM\@GENETIK.UNI-KOELN.DE}, Pages = {749-95}, Pubmed = {9143706}, Title = {Cellular responses to interferon-gamma}, Uuid = {53DA529F-9CC9-4695-996E-301370A9D6A1}, Volume = {15}, Year = {1997}, url = {papers/Boehm_AnnuRevImmunol1997.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.immunol.15.1.749}} @article{Bohatschek:2001, Abstract = {Changes in the morphology of ramified microglia are a common feature in brain pathology and culminate in the appearance of small, rounded, microglia-derived phagocytes in the presence of neural debris. Here, we explored the effect of adding brain cell membranes on the morphology of alphaMbeta2-integrin (CD11b/CD18, CR3) positive microglia cultured on a confluent astrocyte substrate as an in vitro model of deramification. Addition of brain membranes led to a loss of microglial ramification, with full transformation to small, rounded, macrophages at 20-40 microg/ml. Time course studies showed a rapid response, with first effects at 1-3 hours, and full transformation at 24-48 hours. Removal of cell membranes and exchange of the culture medium led to a similarly rapid process of reramification. Comparison of cell membranes from different tissues at 20 microg/ml showed strong transforming effect for the brain, more moderate for kidney and liver, and very weak for spleen and skeletal muscle. Fluorescent labeling of brain membranes revealed uptake by almost all rounded macrophages, by a subpopulation of glial fibrillary acidic protein (GFAP)-positive astrocytes, but not by ramified microglia. Phagocytosis of inert fluorobeads did not lead to a transformation into macrophages but their phagocytosis was inhibited by brain membranes, pointing to a saturable uptake mechanism. In summary, addition of brain cell membranes and their phagocytosis leads to a rapid and reversible loss of ramification. The differences in transforming activity from different tissues and the absence of effect from phagocytosed fluorobeads suggest, however, the need for a second stimulus following the phagocytosis of cell debris.}, Author = {Bohatschek, M. and Kloss, C. U. and Kalla, R. and Raivich, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Dose-Response Relationship, Drug;Cell Differentiation;Animals;Astrocytes;Cells, Cultured;Coculture Techniques;Viscera;Microglia;Models, Biological;Cell Membrane;Cell Movement;11 Glia;Phagocytes;Brain Diseases;Time Factors;Microspheres;Animals, Newborn;Macrophage-1 Antigen;Cell Size;Gliosis;Mice;Immunohistochemistry;Membrane Proteins;Microscopy, Electron;Research Support, Non-U.S. Gov't}, Medline = {21286590}, Month = {6}, Nlm_Id = {7600111}, Number = {5}, Organization = {Department of Neuromorphology, Max-Planck Institute for Neurobiology, Martinsried, Germany.}, Pages = {508-22}, Pubmed = {11391706}, Title = {In vitro model of microglial deramification: ramified microglia transform into amoeboid phagocytes following addition of brain cell membranes to microglia-astrocyte cocultures}, Uuid = {CD0337AF-3415-418B-947B-1E742A854CF3}, Volume = {64}, Year = {2001}} @article{Boire:2005, Abstract = {The laminar distribution of several distinct populations of neurofilament protein containing neurons has been used as a criterion for the delineation of cortical areas in hamsters. SMI-32 is a monoclonal antibody that recognizes a non-phosphorylated epitope on the medium- and high-molecular weight subunits of neurofilament proteins. As in carnivores and primates, SMI-32 immunoreactivity in the hamster neocortex was present in cell bodies, proximal dendrites and axons of some medium and large pyramidal neurons located in cortical layers III, V and VI. A small population of labeled multipolar cells was also found in layer IV. Neurofilament protein immunoreactive neurons were found throughout isocortical areas. Very few labeled cells were encountered in supplemental motor area, insular cortex, medial portion of associative visual cortex and in parietal association cortex. Our data indicate that SMI-32 immunoreactive cells can be efficiently used to trace boundaries between neocortical areas in the hamster's brain. The regional distribution SMI-32 immunoreactivity in the hamster cortex corresponds quite closely with cortical areas as defined by their cytoarchitecture and myeloarchitecture. The primary sensory cortical areas contain the most intense of SMI-32 immunoreactivity and are also those with the highest density of myelinated axons. Very low SMI-32 immunoreactivity was found in orbital, insular, perirhinal, cingulate and infralimbic cortices, which are also poor in myelinated axons. This supports the association between SMI-32 immunoreactivity and myelin contents.}, Author = {Boire, Denis and Desgent, S{\'e}bastien and Matteau, Isabelle and Ptito, Maurice}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0891-0618}, Journal = {J Chem Neuroanat}, Keywords = {23 Technique}, Month = {5}, Nlm_Id = {8902615}, Number = {3}, Organization = {Ecole d'optom{\'e}trie, Universit{\'e} de Montr{\'e}al, CP 6128 succ Centre-Ville, Montr{\'e}al, Quebec, Canada H3C 3J7.}, Pages = {193-208}, Pii = {S0891-0618(05)00017-7}, Pubmed = {15820621}, Title = {Regional analysis of neurofilament protein immunoreactivity in the hamster's cortex}, Uuid = {FC813E7F-D31C-11D9-A0E9-000D9346EC2A}, Volume = {29}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jchemneu.2005.01.003}} @article{Bolz:2004, Abstract = {The functional architecture of the cerebral cortex is based on intrinsic connections that precisely link neurons from distinct cortical laminae as well as layer-specific afferent and efferent projections. Experimental strategies using in vitro assays originally developed by Friedrich Bonhoeffer have suggested that positional cues confined to individual layers regulate the assembly of local cortical circuits and the formation of thalamocortical projections. One of these wiring molecules is ephrinA5, a ligand for Eph receptor tyrosine kinases. EphrinA5 and Eph receptors exhibit highly dynamic expression patterns in distinct regions of the cortex and thalamus during early and late stages of thalamocortical and cortical circuit formation. In vitro assays suggest that ephrinA5 is a multifunctional wiring molecule for different populations of cortical and thalamic axons. Additionally, the expression patterns of ephrinA5 during cortical development are consistent with this molecule regulating, in alternative ways, specific components of thalamic and cortical connectivity. To test this directly, the organization of thalamocortical projections was examined in mice lacking ephrinA5 gene expression. The anatomical studies in ephrinA5 knockout animals revealed a miswiring of limbic thalamic projections and changes in neocortical circuits that were predicted from the expression pattern and the in vitro analysis of ephrinA5 function.}, Author = {Bolz, J{\"u}rgen and Uziel, Daniela and M{\"u}hlfriedel, Sven and G{\"u}llmar, Andr{\'e} and Peuckert, Christiane and Zarbalis, Konstantionos and Wurst, Wolfgang and Torii, Masaaki and Levitt, Pat}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Embryo, Mammalian;Neurons;24 Pubmed search results 2008;10 Development;research support, non-u.s. gov't;Embryo, Nonmammalian;Ephrin-A5;Neural Pathways;10 circuit formation;in vitro;Receptor, EphA1;research support, u.s. gov't, p.h.s.;Animals;Thalamus;Cerebral Cortex;review;Axons}, Month = {4}, Nlm_Id = {0213640}, Number = {1}, Organization = {Universit{\"a}t Jena, Institut f{\"u}r Allgemeine Zoologie und Tierphysiologie, Erberstrasse 1, 07743 Jena, Germany. bolz\@pan.zoo.uni-jena.de}, Pages = {82-94}, Pubmed = {15007829}, Title = {Multiple roles of ephrins during the formation of thalamocortical projections: maps and more}, Uuid = {C6FFBF29-2055-4EB3-8D8B-CFC457E294FB}, Volume = {59}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.10346}} @article{Bond:2002, Abstract = {One of the most notable trends in mammalian evolution is the massive increase in size of the cerebral cortex, especially in primates. Humans with autosomal recessive primary microcephaly (MCPH) show a small but otherwise grossly normal cerebral cortex associated with mild to moderate mental retardation. Genes linked to this condition offer potential insights into the development and evolution of the cerebral cortex. Here we show that the most common cause of MCPH is homozygous mutation of ASPM, the human ortholog of the Drosophila melanogaster abnormal spindle gene (asp), which is essential for normal mitotic spindle function in embryonic neuroblasts. The mouse gene Aspm is expressed specifically in the primary sites of prenatal cerebral cortical neurogenesis. Notably, the predicted ASPM proteins encode systematically larger numbers of repeated 'IQ' domains between flies, mice and humans, with the predominant difference between Aspm and ASPM being a single large insertion coding for IQ domains. Our results and evolutionary considerations suggest that brain size is controlled in part through modulation of mitotic spindle activity in neuronal progenitor cells.}, Author = {Bond, Jacquelyn and Roberts, Emma and Mochida, Ganesh H. and Hampshire, Daniel J. and Scott, Sheila and Askham, Jonathan M. and Springell, Kelly and Mahadevan, Meera and Crow, Yanick J. and Markham, Alexander F. and Walsh, Christopher A. and Woods, C. Geoffrey}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Sequence Analysis, DNA;10 Development;Microtubule-Associated Proteins;Humans;Female;Microcephaly;Anthropometry;research support, non-u.s. gov't;Male;Blotting, Northern;10 genetics malformation;research support, u.s. gov't, p.h.s.;Cerebral Cortex;Pedigree;Codon, Nonsense;24 Pubmed search results 2008;Nerve Tissue Proteins;Drosophila Proteins}, Month = {10}, Nlm_Id = {9216904}, Number = {2}, Organization = {Molecular Medicine Unit, University of Leeds, St. James's University Hospital, Beckett Street, Leeds LS9 7TF, UK.}, Pages = {316-20}, Pii = {ng995}, Pubmed = {12355089}, Title = {ASPM is a major determinant of cerebral cortical size}, Uuid = {F9974529-C060-48CF-852E-667253772176}, Volume = {32}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ng995}} @article{Bondolfi:2002, Abstract = {APP23 transgenic mice express mutant human amyloid precursor protein and develop amyloid plaques predominantly in neocortex and hippocampus progressively with age, similar to Alzheimer's disease. We have previously reported neuron loss in the hippocampal CA1 region of 14- to 18-month-old APP23 mice. In contrast, no neuron loss was found in neocortex. In the present study we have reinvestigated neocortical neuron numbers in adult and aged APP23 mice. Surprisingly, results revealed that 8-month-old APP23 mice have 13 and 14\%more neocortical neurons compared with 8-month-old wild-type and 27-month-old APP23 mice, respectively. In 27-month-old APP23 mice we found an inverse correlation between amyloid load and neuron number. These results suggest that APP23 mice have more neurons until they develop amyloid plaques but then lose neurons in the process of cerebral amyloidogenesis. Supporting this notion, we found more neurons with a necrotic-apoptotic phenotype in the neocortex of 24-month-old APP23 mice compared with age-matched wild-type mice. Stimulated by recent reports that demonstrated neurogenesis after targeted neuron death in the mouse neocortex, we have also examined neurogenesis in APP23 mice. Strikingly, we found a fourfold to sixfold increase in newly produced cells in 24-month-old APP23 mice compared with both age-matched wild- type mice and young APP23 transgenic mice. However, subsequent cellular phenotyping revealed that none of the newly generated cells in neocortex had a neuronal phenotype. The majority were microglial and to a lesser extent astroglial cells. We conclude that cerebral amyloidosis in APP23 mice causes a modest neuron loss in neocortex and induces marked gliogenesis.}, Author = {Bondolfi, L. and Calhoun, M. and Ermini, F. and Kuhn, H. G. and Wiederhold, K. H. and Walker, L. and Staufenbiel, M. and Jucker, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Neocortex/*metabolism/pathology;Human;Amyloidosis/*metabolism/pathology;Neurons/*metabolism/pathology;Alzheimer Disease/metabolism/pathology;G;Phenotype;Female;Cell Count;Animal;Mice, Transgenic;Neuroglia/*metabolism/pathology;11 Glia;Mice, Inbred C57BL;Male;Amyloid beta-Protein Precursor/*genetics;Support, Non-U.S. Gov't;In Situ Nick-End Labeling;Mice;Aging/metabolism/pathology;Cell Division;Bromodeoxyuridine;Cell Death}, Number = {2}, Organization = {Department of Neuropathology, Institute of Pathology, University of Basel, CH-4003 Basel, Switzerland.}, Pages = {515-22.}, Title = {Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice}, Uuid = {BF2CAC95-97F5-4657-B001-863B64C3C59B}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11784797%20http://www.jneurosci.org/cgi/content/full/22/2/515%20http://www.jneurosci.org/cgi/content/abstract/22/2/515}} @article{Bonfanti:2006, Abstract = {Polysialic acid (PSA) is a linear homopolymer of alpha2-8-N acetylneuraminic acid whose major carrier in vertebrates is the neural cell adhesion molecule (NCAM). PSA serves as a potent negative regulator of cell interactions via its unusual biophysical properties. PSA on NCAM is developmentally regulated thus playing a prominent role in different forms of neural plasticity spanning from embryonic to adult nervous system, including axonal growth, outgrowth and fasciculation, cell migration, synaptic plasticity, activity-induced plasticity, neuronal-glial plasticity, embryonic and adult neurogenesis. The cellular distribution, developmental changes and possible function(s) of PSA-NCAM in the central nervous system of mammals here are reviewed, along with recent findings and theories about the relationships between NCAM protein and PSA as well as the role of different polysialyltransferases. Particular attention is focused on postnatal/adult neurogenesis, an issue which has been deeply investigated in the last decade as an example of persisting structural plasticity with potential implications for brain repair strategies. Adult neurogenic sites, although harbouring all subsequent steps of cell differentiation, from stem cell division to cell replacement, do not faithfully recapitulate development. After birth, they undergo morphological and molecular modifications allowing structural plasticity to adapt to the non-permissive environment of the mature nervous tissue, that are paralled by changes in the expression of PSA-NCAM. The use of PSA-NCAM as a marker for exploring differences in structural plasticity and neurogenesis among mammalian species is also discussed.}, Author = {Bonfanti, Luca}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0370121}, Number = {3}, Organization = {Department of Veterinary Morphophysiology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco, Italy; Rita Levi Montalcini Center for Brain Repair, Turin, Italy.}, Pages = {129-64}, Pii = {S0301-0082(06)00108-0}, Pubmed = {17029752}, Title = {PSA-NCAM in mammalian structural plasticity and neurogenesis}, Uuid = {CCE82151-1E30-4A24-99CB-36C03A706EFA}, Volume = {80}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.pneurobio.2006.08.003}} @article{Bonneau:2007, Abstract = {The environment significantly influences the dynamic expression and assembly of all components encoded in the genome of an organism into functional biological networks. We have constructed a model for this process in Halobacterium salinarum NRC-1 through the data-driven discovery of regulatory and functional interrelationships among approximately 80\%of its genes and key abiotic factors in its hypersaline environment. Using relative changes in 72 transcription factors and 9 environmental factors (EFs) this model accurately predicts dynamic transcriptional responses of all these genes in 147 newly collected experiments representing completely novel genetic backgrounds and environments-suggesting a remarkable degree of network completeness. Using this model we have constructed and tested hypotheses critical to this organism's interaction with its changing hypersaline environment. This study supports the claim that the high degree of connectivity within biological and EF networks will enable the construction of similar models for any organism from relatively modest numbers of experiments.}, Author = {Bonneau, Richard and Facciotti, Marc T. and Reiss, David J. and Schmid, Amy K. and Pan, Min and Kaur, Amardeep and Thorsson, Vesteinn and Shannon, Paul and Johnson, Michael H. and Bare, J. Christopher and Longabaugh, William and Vuthoori, Madhavi and Whitehead, Kenia and Madar, Aviv and Suzuki, Lena and Mori, Tetsuya and Chang, Dong-Eun E. and Diruggiero, Jocelyne and Johnson, Carl H. and Hood, Leroy and Baliga, Nitin S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Transcription, Genetic;Transcription Factors;Systems Biology;Databases, Genetic;20 Networks;Models, Genetic;RNA, Messenger;Time Factors;Gene Expression Regulation, Archaeal;Adaptation, Physiological;Environment;research support, n.i.h., extramural;Archaeal Proteins;Reproducibility of Results;24 Pubmed search results 2008;Gene Regulatory Networks;research support, u.s. gov't, non-p.h.s.;Sodium Chloride;Halobacterium salinarum}, Month = {12}, Nlm_Id = {0413066}, Number = {7}, Organization = {Center for Genomics & Systems Biology, New York University, New York, NY 10003, USA; Courant Institute of Mathematical Sciences, Department of Computer Science, New York University, New York, NY 10003, USA.}, Pages = {1354-65}, Pii = {S0092-8674(07)01416-X}, Pubmed = {18160043}, Title = {A predictive model for transcriptional control of physiology in a free living cell}, Uuid = {674AADE6-FC75-4A51-B28C-E639F8F691FC}, Volume = {131}, Year = {2007}, url = {papers/Bonneau_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2007.10.053}} @article{Bordey:2006, Abstract = {Findings over the past decades demonstrating persistent neurogenesis in the adult brain have challenged the view of a fixed circuitry in normally functioning brain and raised hopes for self-renewal following brain injury. In addition to providing insights for repair, studying adult neurogenesis may improve our understanding of embryonic development assuming that fundamental mechanisms are similar. It is argued here, using examples of cell:cell communication, that parallels can be drawn between adult and embryonic neurogenesis. Paradoxically, cell:cell communication in neurogenic regions resembles that in a mature neuroglial network. This suggests that differences in the integrative properties of cells and the extracellular matrix molecules may constitute a neurogenic environment or "niche". While reasons for persistent adult neurogenesis in humans remains obscure, recent findings regarding the environmental and activity-driven control of neurogenesis reinforce the original concept of a role for neurogenesis in motor memory formation and refinement of information processing.}, Author = {Bordey,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {1551-4005}, Journal = {Cell Cycle}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {101137841}, Number = {7}, Pii = {2614}, Pubmed = {16582623}, Title = {Adult Neurogenesis: Basic Concepts of Signaling}, Uuid = {6321DE64-188A-4C4C-A4D7-BAD0AF248B82}, Volume = {5}, Year = {2006}} @article{Borlongan:1998, Abstract = {This study was designed to explore the efficacy of a human clone cell line as an alternative neural graft source and to validate the practice of cryopreservation and xenografting as logistical approaches toward conducting neural transplantation. We investigated the biological effects of transplanting cultured human neurons (NT2N cells) derived from a well-characterized embryonal carcinoma cell line into the brains of rats subjected to transient, focal cerebral ischemia induced by embolic occlusion of the middle cerebral artery. At 1 month and extending throughout the 6-month posttransplantation test period, ischemic animals that were transplanted with NT2N cells and treated with an immunosuppressive drug displayed a significant improvement in a passive avoidance task as well as a normalization of asymmetrical motor behavior compared to ischemic animals that received rat fetal cerebellar cell grafts or vehicle alone. Remarkably, cryopreserved NT2N cell grafts compared with fresh NT2N cell grafts, remained viable in the immunosuppressed rat brain and effective in producing behavioral recovery in immunosuppressed ischemic animals. The long-term viability of cryopreserved NT2N cell xenografts in vivo and their sustained effectiveness in promoting behavioral recovery suggest potential utilization of xenografting and cryopreservation as useful protocols for establishing clone cell lines as graft source in neural transplantation therapies for central nervous system disorders. 0014-4886 Journal Article}, Author = {Borlongan, C. V. and Tajima, Y. and Trojanowski, J. Q. and Lee, V. M. and Sanberg, P. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Exp Neurol}, Keywords = {*Graft Survival;Human;Cerebral Arteries;Motor Activity;Immunosuppressive Agents/therapeutic use;Animals;Carcinoma, Embryonal/*pathology;*Cryopreservation;Rats;Comparative Study;Rats, Sprague-Dawley;Brain/pathology;Avoidance Learning;Ischemic Attack, Transient/pathology/*physiopathology/*surgery;Fetal Tissue Transplantation;17 Transplant Regeneration;Male;Neurons/cytology/pathology/*transplantation;Cell Line;Support, Non-U.S. Gov't;*Transplantation, Heterologous;L abstr;Tumor Cells, Cultured;Cerebellum/transplantation;Support, U.S. Gov't, P.H.S.;Reproducibility of Results;*Brain Tissue Transplantation}, Number = {2}, Organization = {Department of Surgery, University of South Florida College of Medicine, Tampa 33612, USA.}, Pages = {310-21}, Title = {Transplantation of cryopreserved human embryonal carcinoma-derived neurons (NT2N cells) promotes functional recovery in ischemic rats}, Uuid = {EEEEDFE7-44E2-41E2-B8AF-082CB5047BB5}, Volume = {149}, Year = {1998}, url = {papers/Borlongan_ExpNeurol1998.pdf}} @article{Borlongan:1998a, Abstract = {Stroke mortality has declined over recent decades, prompting a demand for the development of effective rehabilitative therapies for stroke survivors. This effort has been facilitated by significant progress in replicating the behavioral and neuropathological changes of authentic human cerebral ischemia using relevant animal models. Since the rodent model of middle cerebral artery occlusion mimics several motor abnormalities seen in clinical cerebral ischemia, we have utilized this model to investigate treatment strategies for stroke. The present study explored the potential benefits of neural transplantation of fetal rat striatal cells or human neurons derived from a clonal embryonal carcinoma cell line to correct the abnormalities associated with cerebral ischemia. We report here that ischemia-induced behavioral dysfunctions were ameliorated by the neural grafts as early as 1 month post-transplantation. Of note, transplantation of human neurons induced a significantly more robust recovery than fetal rat striatal grafts. Thus, the logistical and ethical concerns about the use of fetal striatal cells for transplantation therapy can be eliminated by exploiting cell line-derived human neurons as alternative graft sources. Transplantation of human neurons has a therapeutic potential for treatment of behavioral deficits associated with cerebral ischemia. 0959-4965 Journal Article}, Author = {Borlongan, C. V. and Tajima, Y. and Trojanowski, J. Q. and Lee, V. M. and Sanberg, P. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuroreport}, Keywords = {Human;Animals;Clone Cells/chemistry/transplantation;Rats;Cerebrovascular Disorders/surgery;*Fetal Tissue Transplantation;Brain Ischemia/*physiopathology/surgery;Rats, Sprague-Dawley;Motor Activity/physiology;Neurons/chemistry/*transplantation;17 Transplant Regeneration;Male;Corpus Striatum/blood supply/*transplantation;Support, Non-U.S. Gov't;L abstr;Graft Survival/physiology;Behavior, Animal/physiology;Avoidance Learning/physiology;Cell Adhesion Molecules, Neuronal/analysis;Locomotion/physiology;*Brain Tissue Transplantation}, Number = {16}, Organization = {National Institutes of Health, National Institute on Drug Abuse, Intramural Research Program, Cellular Neurophysiology, Baltimore, MD 21224, USA.}, Pages = {3703-9}, Pubmed = {9858383}, Title = {Cerebral ischemia and CNS transplantation: differential effects of grafted fetal rat striatal cells and human neurons derived from a clonal cell line}, Uuid = {82E239B6-7AB1-4AFE-8F2E-FA6D89B0273B}, Volume = {9}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9858383}} @article{Borrell:2006, Abstract = {Cajal-Retzius cells are critical in the development of the cerebral cortex, but little is known about the mechanisms controlling their development. Three focal sources of Cajal-Retzius cells have been identified in mice-the cortical hem, the ventral pallium and the septum-from where they migrate tangentially to populate the cortical surface. Using a variety of tissue culture assays and in vivo manipulations, we demonstrate that the tangential migration of cortical hem-derived Cajal-Retzius cells is controlled by the meninges. We show that the meningeal membranes are a necessary and sufficient substrate for the tangential migration of Cajal-Retzius cells. We also show that the chemokine CXCL12 secreted by the meninges enhances the dispersion of Cajal-Retzius cells along the cortical surface, while retaining them within the marginal zone in a CXCR4-dependent manner. Thus, the meningeal membranes are fundamental in the development of Cajal-Retzius cells and, hence, in the normal development of the cerebral cortex.}, Author = {Borrell, V{\'\i}ctor and Mar{\'\i}n, Oscar}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, non-u.s. gov't ;Epithelial Cells;Green Fluorescent Proteins;Laminin;Heterocyclic Compounds;24 Pubmed search results 2008;Cerebral Cortex;Animals;Cells, Cultured;Receptors, CXCR4;comparative study ;Cell Movement;Signal Transduction;Meninges;Organ Culture Techniques;Extracellular Matrix Proteins;Calcium-Binding Protein, Vitamin D-Dependent;In Situ Hybridization;Transplants;Serine Endopeptidases;Chemokines, CXC;Fluorescent Antibody Technique;Indoles;Embryo;Cell Adhesion Molecules, Neuronal;Mice, Inbred ICR;Mice;Neurons;Mice, Transgenic;in vitro ;Nerve Tissue Proteins}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Cient{\'\i}ficas & Universidad Miguel Hern{\'a}ndez, 03550 Sant Joan d'Alacant, Spain.}, Pages = {1284-93}, Pii = {nn1764}, Pubmed = {16964252}, Title = {Meninges control tangential migration of hem-derived Cajal-Retzius cells via CXCL12/CXCR4 signaling}, Uuid = {735C9844-69E2-4069-9467-0E08874F69F7}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1764}} @article{Boss:1985, Abstract = {We have estimated the number of dentate granule cells in Sprague-Dawley and Wistar rats at 1, 4 and 12 months of age. In Sprague-Dawley rats the number of granule cells is relatively constant throughout this period at about 1 million. In Wistar rats, on the other hand, there is a progressive increase in the number from about 700,000 at 1 month to 1 million at 4 months; thereafter the number declines to about 800,000 at 1 year. Estimates of the numbers of cells in the polymorphic zone that can be stained immunohistochemically for somatostatin, cholecystokinin, vasoactive-intestinal peptide, and glutamic acid decarboxylase show no appreciable differences in the two strains.}, Author = {Boss, B. D. and Peterson, G. M. and Cowan, W. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {10 Development;10 Hippocampus;Animals;Rats;Comparative Study;Immunoenzyme Techniques;Female;Cell Count;Hippocampus;Rats, Inbred Strains;Vasoactive Intestinal Peptide;Cholecystokinin;Male;Brain Chemistry;Glutamate Decarboxylase;Neurons;Age Factors;Nerve Tissue Proteins;Serotonin}, Medline = {85281338}, Month = {7}, Nlm_Id = {0045503}, Number = {1}, Pages = {144-50}, Pubmed = {3896391}, Title = {On the number of neurons in the dentate gyrus of the rat}, Uuid = {6EE3FE21-446E-437E-8E5D-E63C232E678B}, Volume = {338}, Year = {1985}} @article{Boucsein:2000, Abstract = {Microglial cells serve as pathologic sensors of the brain. They are highly abundant in all regions of the central nervous system (CNS) and are characterized by a ramified morphology within the normal tissue. In the present study, we have developed a procedure to study the membrane properties of identified, in situ microglia in acutely isolated brain slices from rat cortex, striatum and facial nucleus. Unlike the well characterized cultured microglial cells, ramified microglia of the slice are characterized by little, if any, voltage-gated membrane currents and a very low membrane potential. They are thus distinct from neurons, other glial cells and nonbrain macrophages. To study the consequences of microglial activation on the membrane channel pattern, we compared cells in the normal facial nucleus and at defined times after facial nerve axotomy. Within 12 h of axotomy, microglial cells expressed a prominent inward rectifier current and thus acquired the physiological properties of cultured microglia. Within 24 h of the lesion, the cells expressed an additional outward current, which is typical for lipopolysaccharide (LPS)-activated microglia in vitro. Seven days after the lesion, at a time of major regenerative processes in the facial nucleus, the physiological properties of microglial cells had reverted to those present prior to the pathological event. In conclusion: (i) ramified microglial cells represent a physiologically unique population of cells in the brain; (ii) are distinct from their cultured counterparts; and (iii), undergo a defined pattern of physiological states in the course of pathologic events.}, Author = {Boucsein, C. and Kettenmann, H. and Nolte, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Plant Lectins;Animals;Cells, Cultured;Rats;Microglia;Female;Patch-Clamp Techniques;Lipopolysaccharides;Rats, Wistar;11 Glia;Animals, Newborn;Support, Non-U.S. Gov't;Potassium Channels;Cerebral Cortex;Cell Size;Membrane Potentials;Axotomy;Facial Nerve;Lectins}, Medline = {20345454}, Month = {6}, Nlm_Id = {8918110}, Number = {6}, Organization = {Max Delbr{\"u}ck Center for Molecular Medicine, Cellular Neuroscience, Robert-R{\"o}ssle-Strabetae 10, D-13092 Berlin, Germany.}, Pages = {2049-58}, Pii = {ejn100}, Pubmed = {10886344}, Title = {Electrophysiological properties of microglial cells in normal and pathologic rat brain slices}, Uuid = {19AEDB8C-0300-4182-91A3-20C255DF94F5}, Volume = {12}, Year = {2000}} @article{Boulanger:2004, Author = {Boulanger, Lisa M. and Shatz, Carla J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Models, Biological;Major Histocompatibility Complex;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Central Nervous System;Neuronal Plasticity;Signal Transduction;Antigens, Surface;14 Immune;Gene Expression;Humans;Animals;Nervous System Diseases;review;Neurons}, Month = {7}, Nlm_Id = {100962781}, Number = {7}, Organization = {Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, Pacific Hall 1212A, 9500 Gilman Drive, La Jolla, California, USA. lboulanger\@ucsd.edu}, Pages = {521-31}, Pii = {nrn1428}, Pubmed = {15208694}, Title = {Immune signalling in neural development, synaptic plasticity and disease}, Uuid = {09A522B5-B622-44D0-A425-E25D4C38969D}, Volume = {5}, Year = {2004}, url = {papers/Boulanger_NatRevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1428}} @article{Bourgeois:1994, Abstract = {Since the turn of the century, the prefrontal association areas of the cerebral cortex have been thought to be among the last regions of the cortical mantle to develop. We have examined the course of synaptogenesis in the macaque prefrontal cortex by quantitative electron microscopic analysis in 25 rhesus monkeys ranging in age from embryonic day 47 (E47) to 20 years of age. A series of overlapping electron micrographs spanning the whole cortical thickness in each animal provided data on the number, the proportion, and the density of synapses per unit area (NA) and per unit volume (NV) of neuropil. The tempo and kinetics of synapse formation in prefrontal cortex closely resemble those described for sensory and motor areas, particularly during the stages of synapse acquisition and overproduction (Rakic et al., 1986). In young embryos, we describe a precortical phase (E47- E78), when synapses are found only above and below, but not within, the cortical plate. Following that, there is an early cortical phase, from E78 to E104, during which synapses accumulate within the cortical plate, initially exclusively on dendritic shafts. The next rapid phase of synaptogenesis begins at 2 months before birth and ends approximately at 2 months after birth, culminating with a mean density of 750 million synapses per cubic micrometer. This accumulation is largely accounted for by a selective increase in axospine synapses in the supragranular layers. The period of explosive synaptic density is followed by a protracted plateau stage that lasts from 2 months to 3 years of age when synaptic density remains relatively constant. The final period of decline, from 3 years through over 20 years of age, is marked by a slight but statistically significant decline in synaptic density. Concurrent recruitment of synapses with that of sensory and motor areas supports the concept that the initial establishment of cortical circuitry is governed by general mechanisms common to all areas, independent of their specific functional domain. The finding that synaptic density is relatively stable from early adolescence through puberty (the plateau period) is indicative of the importance, in primates, of a consistent and high synaptic density during the formative years when learning experiences are most intense.}, Author = {Bourgeois, J. P. and Goldman-Rakic, P. S. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cereb Cortex}, Keywords = {10 Development;Prefrontal Cortex/embryology/*growth &development/ultrastructure;Synapses/*physiology;Female;Microscopy, Electron;Macaca mulatta;Dendrites/physiology;Aging/physiology;Animal;Pregnancy;F;Support, U.S. Gov't, P.H.S.;Male}, Number = {1}, Organization = {Departement des Biotechnologies, Institut Pasteur, Paris, France.}, Pages = {78-96.}, Title = {Synaptogenesis in the prefrontal cortex of rhesus monkeys}, Uuid = {BD68D4F7-1CC6-4F6E-B07F-C017550DBA38}, Volume = {4}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8180493}} @article{Bourne:2005, Abstract = {The maturation of pyramidal neurons in the primary visual cortex (V1) of marmoset monkeys was investigated using an antibody (SMI-32) to non-phosphorylated neurofilament protein (NNF). Analysis of animals aged between birth and postnatal day 91 (PD 91, which corresponds approximately to the peak of synaptogenesis in this species) revealed discrete changes in both the laminar and the areal distribution of NNF. At PD 0, the upper part of layer 6 contained darkly labelled neurons and associated neuropil, including axons. In this layer a centroperipheral gradient, with more labelled cells in the foveal representation, was apparent at PD 0. This topographic gradient gradually disappeared, and by PD 91 a similar density of labelled layer 6 cells was observed throughout V1. Labelled cells were not apparent in layer 3C until PD 7, and were not distributed according to a topographic gradient. Labelled cells were first observed in layer 3B(alpha) at PD 28, when they formed a centroperipheral gradient similar to that seen in layer 6. This gradient was still evident in an adult animal. These results demonstrate an inside-out profile of postnatal cortical development, with the topographic pattern of maturation of V1 mimicking the centroperipheral gradient of maturation in the retina.}, Author = {Bourne, James A. and Warner, Claire E. and Rosa, Marcello G. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {23 Technique}, Month = {6}, Nlm_Id = {9110718}, Number = {6}, Organization = {Department of Physiology and Monash University Centre for Brain and Behaviour, Monash University, Victoria 3800, Australia. james.bourne\@med.monash.edu.au}, Pages = {740-8}, Pii = {bhh175}, Pubmed = {15342427}, Title = {Topographic and laminar maturation of striate cortex in early postnatal marmoset monkeys, as revealed by neurofilament immunohistochemistry}, Uuid = {A447C9C8-A27C-4B24-BD38-6B78C473BFB5}, Volume = {15}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh175}} @article{Bouzioukh:2001, Abstract = {Here we report that synapses in the adult dorsal vagal complex, a gateway for many primary afferent fibers, express a high level of the polysialylated neural cell adhesion molecule (PSA-NCAM). We show that electrical stimulation of the vagal afferents causes a rapid decrease of PSA-NCAM expression both in vivo and in acute slices. Inhibition of NMDA receptor activity completely prevented the decrease. Blockade of calmodulin activation, neuronal nitric oxide (NO) synthase, or soluble guanylyl cyclase and chelation of extracellular NO mimicked this inhibition. Our data provide a mechanistic framework for understanding how activity-linked stimulation of the NMDA-NO-cGMP pathway induces rapid changes in PSA-NCAM expression, which may be associated with long- term depression.}, Author = {Bouzioukh, F. and Tell, F. and Jean, A. and Rougon, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Vagus Nerve/physiology;Nitric-Oxide Synthase/antagonists &inhibitors/*metabolism;Electric Stimulation;Guanylate Cyclase/antagonists &inhibitors/metabolism;Neural Cell Adhesion Molecules/*biosynthesis;In Vitro;Rats;Nitric Oxide/antagonists &inhibitors/metabolism;Neuronal Plasticity/physiology;Receptors, N-Methyl-D-Aspartate/antagonists &inhibitors/*metabolism;Chelating Agents/pharmacology;Animal;Rats, Sprague-Dawley;Enzyme Inhibitors/pharmacology;Brain Stem/*metabolism;Synapses/*metabolism;Support, Non-U.S. Gov't;Neurons, Afferent/physiology;Cyclic GMP/metabolism;C;04 Adult neurogenesis factors;Neural Inhibition/physiology;Calmodulin/antagonists &inhibitors/metabolism;Sialic Acids/*biosynthesis;Signal Transduction/physiology;GAP-43 Protein/biosynthesis}, Number = {13}, Organization = {Faculte de Saint Jerome, Centre National de la Recherche Scientifique (CNRS) Formation de Recherche en Evolution 2132-Unite Sous Contrat Institut National de la Recherche Agronomique 1147, 13397 Marseille, Cedex 20, France.}, Pages = {4721-30.}, Title = {NMDA receptor and nitric oxide synthase activation regulate polysialylated neural cell adhesion molecule expression in adult brainstem synapses}, Uuid = {299175EC-6366-44F0-8FF0-B61D5C83C861}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11425899%20http://www.jneurosci.org/cgi/content/full/21/13/4721%20http://www.jneurosci.org/cgi/content/abstract/21/13/4721}} @article{Bragin:1999, Abstract = {PURPOSE: Properties of oscillations with frequencies >100 Hz were studied in kainic acid (KA)-treated rats and compared with those recorded in normal and kindled rats as well as in patients with epilepsy to determine differences associated with epilepsy. METHODS: Prolonged in vivo wideband recordings of electrical activity were made in hippocampus and entorhinal cortex (EC) of (a) normal rats, (b) kindled rats, (c) rats having chronic recurrent spontaneous seizures after intrahippocampal KA injections, and (d) patients with epilepsy undergoing depth electrode evaluation in preparation for surgical treatment. RESULTS: Intermittent oscillatory activity ranging from 100 to 200 Hz in frequency and 50-150 ms in duration was recorded in CA1 and EC of all three animal groups, and in epileptic human hippocampus and EC. This activity had the same characteristics in all groups, resembled previously observed "ripples" described by Buzs{\'a}ki et al., and appeared to represent field potentials of inhibitory postsynaptic potentials (IPSPs) on principal cells. Unexpectedly, higher frequency intermittent oscillatory activity ranging from 200 to 500 Hz and 10-100 ms in duration was encountered only in KA-treated rats and patients with epilepsy. These oscillations, termed fast ripples (FRs), were found only adjacent to the epileptogenic lesion in hippocampus, EC, and dentate gyrus, and appeared to represent field potential population spikes. Their local origin was indicated by correspondence with the negative phase of burst discharges of putative pyramidal cells. CONCLUSIONS: The persistence of normal-appearing ripples in epileptic brain support the view that inhibitory processes are preserved. FRs appear to be field potentials reflecting hyper-synchronous bursting of excitatory neurons and provide an opportunity to study the role of this pathophysiologic phenomenon in epilepsy and seizure initiation. Furthermore, if FR activity is unique to brain areas capable of generating spontaneous seizures, its identification could be a powerful functional indicator of the epileptic region in patients evaluated for surgical treatment.}, Author = {Bragin, A. and Engel, J. and Wilson, C. L. and Fried, I. and Mathern, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:41 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Electric Stimulation;Electrophysiology;Animals;Humans;Rats;Seizures;Functional Laterality;Entorhinal Cortex;Rats, Sprague-Dawley;Hippocampus;Kainic Acid;Male;Action Potentials;Epilepsy, Temporal Lobe;21 Neurophysiology;research support, u.s. gov't, p.h.s.;21 Gap junctions;24 Pubmed search results 2008;Interneurons;Microelectrodes;Electroencephalography;Electrodes, Implanted;Kindling, Neurologic}, Month = {2}, Nlm_Id = {2983306R}, Number = {2}, Organization = {Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California 90095-1769, USA.}, Pages = {127-37}, Pubmed = {9952257}, Title = {Hippocampal and entorhinal cortex high-frequency oscillations (100--500 Hz) in human epileptic brain and in kainic acid--treated rats with chronic seizures}, Uuid = {E9EF4A1B-54A6-41F3-8E05-EDE25F13189B}, Volume = {40}, Year = {1999}, url = {papers/Bragin_Epilepsia1999.pdf}} @article{Bragin:2002, Abstract = {Aperiodic high-frequency oscillations (>100 Hz) reflect a short-term synchronization of neuronal electrical activity. It has been shown in the epileptic brain that spontaneous oscillations in the frequency range of 250-600 Hz reflect action potential population bursts of synchronously discharging neuronal clusters. These oscillations occur in the early stages of epileptogenesis in areas adjacent to the brain lesion and may trigger the formation of seizure-generating neuronal networks. We studied the extent of the area generating oscillations in the frequency range of 250-600 Hz [fast ripples (FRs)] in intrahippocampal kainic acid-treated rats with spontaneous seizures, by analyzing voltage versus depth profiles of FRs in hippocampal and parahippocampal areas in freely moving animals and by spatial mapping in hippocampal slice preparations in vitro. The strength of inhibition was compared in areas with and without FRs using a paired-pulse paradigm. The extent of the areas generating FRs did not exceed 1 mm(3). The areas generating FRs became broader after the application of the GABA(A) receptor antagonist bicuculline. Paired-pulse fast inhibition at 15-30 msec intervals was similar in areas generating FRs and areas not generating FRs. Our data illustrate that hypothesized clusters of highly interconnected neurons are capable of overcoming interneuron feedback inhibition, resulting in generation of epileptiform bursts, eventually leading to seizure activity.}, Author = {Bragin, Anatol and Mody, Istvan and Wilson, Charles L. and Engel, Jerome}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {in vitro;Electric Stimulation;Animals;Evoked Potentials;Rats;Feedback;Brain;Epilepsy;Rats, Sprague-Dawley;Perforant Pathway;Hippocampus;Biological Clocks;Kainic Acid;Chronic Disease;Reaction Time;Entorhinal Cortex;Disease Models, Animal;Male;Action Potentials;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Dentate Gyrus;GABA Antagonists;24 Pubmed search results 2008;Microelectrodes;Neural Inhibition;Brain Mapping}, Month = {3}, Nlm_Id = {8102140}, Number = {5}, Organization = {Department of Neurology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1769, USA. abragin\@ucla.edu}, Pages = {2012-21}, Pii = {22/5/2012}, Pubmed = {11880532}, Title = {Local generation of fast ripples in epileptic brain}, Uuid = {1826D7CE-B5A1-40D8-AAD5-ED4F5D3926FD}, Volume = {22}, Year = {2002}, url = {papers/Bragin_JNeurosci2002.pdf}} @article{Bragin:2004, Abstract = {The normal processes of learning and memory as well as the pathological progress of various neurological diseases may result in changes in gene expression in small, local populations of neurons in any given brain area, leading to the occurrence of specific patterns of electrical activity without easily detectable changes in the morphology of this brain area. One way of identifying these changes might be the comparison of gene expression of areas which generate and areas which do not generate specific patterns of electrical activity. A method for microbiopsy of limited (0.5-1.0 mm3) tissue samples from electrophysiologically identified areas of neurons generating epileptiform activity in the rat brain is described. Here we demonstrate that total RNA isolated from individual microbiopsy samples might be successfully used for microarray based gene expression analysis of any discretely localized neuronal group which can be identified electrophysiologically, including neurons in cortical columns, cell assemblies or other functional units.}, Author = {Bragin, Anatol and Karsten, Stanislav L. and Almajano, Joyel and Wilson, Charles L. and Geschwind, Daniel H. and Engel, Jerome}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Electrophysiology;Animals;RNA;Rats;Comparative Study;Oligonucleotide Array Sequence Analysis;Brain;21 Epilepsy;Epilepsy;Hippocampus;Rats, Wistar;Kainic Acid;Disease Models, Animal;Male;Biopsy;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Neurons;Laterality;Polymerase Chain Reaction;24 Pubmed search results 2008;Microelectrodes;Research Support, Non-U.S. Gov't}, Month = {2}, Nlm_Id = {7905558}, Number = {1-2}, Organization = {Department of Neurology, Seizure Disorder Center, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA. abragin\@ucla.edu}, Pages = {49-55}, Pii = {S0165027003003121}, Pubmed = {14757344}, Title = {Large-scale microarray gene expression analysis in discrete electrophysiologically identified neuronal clusters}, Uuid = {2FDB5A3F-8231-488F-B08D-EB5F2E544AFF}, Volume = {133}, Year = {2004}, url = {papers/Bragin_JNeurosciMethods2004.pdf}} @article{Brainard:2002, Abstract = {Bird fanciers have known for centuries that songbirds learn their songs. This learning has striking parallels to speech acquisition: like humans, birds must hear the sounds of adults during a sensitive period, and must hear their own voice while learning to vocalize. With the discovery and investigation of discrete brain structures required for singing, songbirds are now providing insights into neural mechanisms of learning. Aided by a wealth of behavioural observations and species diversity, studies in songbirds are addressing such basic issues in neuroscience as perceptual and sensorimotor learning, developmental regulation of plasticity, and the control and function of adult neurogenesis. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Brainard, M. S. and Doupe, A. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Nature}, Keywords = {Prosencephalon/cytology/growth &development/*physiology;01 Adult neurogenesis general;Hearing/physiology;Learning/*physiology;Motor Cortex/cytology/growth &development/physiology;Human;Female;Neuronal Plasticity;Synapses/physiology;Aging/physiology;Auditory Cortex/cytology/growth &development/physiology;Support, U.S. Gov't, P.H.S.;Songbirds/*physiology;Vocalization, Animal/*physiology;Animals;Support, Non-U.S. Gov't;A pdf}, Number = {6886}, Organization = {W.M Keck Center for Integrative Neuroscience, University of California, San Francisco 94143, USA. msb\@phy.ucsf.edu}, Pages = {351-8}, Title = {What songbirds teach us about learning}, Uuid = {9399E62F-21B2-40AA-AD00-F71704628300}, Volume = {417}, Year = {2002}, url = {papers/Brainard_Nature2002}} @article{Brauer:1982, Abstract = {Perineuronal nets could be visualized with some Golgi methods in the rat's brain. Nets were seen in telencephalic, diencephalic and mesencephalic structures covering somata and proximal dendrites of different neuronal types. Some nets could be found originating from microglia cells. In most cases their origin is not recognizable. These perineuronal nets seem to be identical with "Golgi nets" of late anatomists, which played an important role in the discussion between recticularists and neuronists. Some aspects of their possible functional significance are discussed.}, Author = {Brauer, K. and Werner, L. and Leibnitz, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0021-8359}, Journal = {J Hirnforsch}, Keywords = {10 Development;Research Support, Non-U.S. Gov't;Dendrites;Golgi Apparatus;Telencephalon;Rats;Mesencephalon;Get paper from library;Neuroglia;Diencephalon;11 Glia;Nervous System;Nerve Net;Animals;10 Structural plasticity;24 Pubmed search results 2008;Neurons}, Medline = {83187585}, Nlm_Id = {0421521}, Number = {6}, Pages = {701-8}, Pubmed = {7169530}, Title = {Perineuronal nets of glia}, Uuid = {6C3CFCD5-8E12-4EEE-8600-084388DB2328}, Volume = {23}, Year = {1982}, url = {papers/Brauer_JHirnforsch1982.PDF}} @article{Bray:1998, Abstract = {Chemotactic bacteria such as Escherichia coli can detect and respond to extremely low concentrations of attractants, concentrations of less than 5 nM in the case of aspartate. They also sense gradients of attractants extending over five orders of magnitude in concentration (up to 1 mM aspartate). Here we consider the possibility that this combination of sensitivity and range of response depends on the clustering of chemotactic receptors on the surface of the bacterium. We examine what will happen if ligand binding changes the activity of a receptor, propagating this change in activity to neighbouring receptors in a cluster. Calculations based on these assumptions show that sensitivity to extracellular ligands increases with the extent of spread of activity through an array of receptors, but that the range of concentrations over which the array works is severely diminished. However, a combination of low threshold of response and wide dynamic range can be attained if the cell has both clusters and single receptors on its surface, particularly if the extent of activity spread can adapt to external conditions. A mechanism of this kind can account quantitatively for the sensitivity and response range of E. coli to aspartate.}, Author = {Bray, D. and Levin, M. D. and Morton-Firth, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Models, Biological;24 Pubmed search results 2008;Ligands;21 Neurophysiology;Aspartic Acid;Membrane Proteins;Receptor Aggregation;Receptors, Amino Acid;Chemotactic Factors;Chemotaxis;Bacterial Proteins;Escherichia coli}, Month = {5}, Nlm_Id = {0410462}, Number = {6680}, Organization = {Department of Zoology, University of Cambridge, UK. d.bray\@zoo.cam.ac.uk}, Pages = {85-8}, Pubmed = {9590695}, Title = {Receptor clustering as a cellular mechanism to control sensitivity}, Uuid = {FD4BB318-4BA3-4F47-B7BF-30748611FA95}, Volume = {393}, Year = {1998}, url = {papers/Bray_Nature1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/30018}} @article{Braz:2002, Abstract = {Systems neuroscience addresses the complex circuits made by populations of neurons in the CNS and the cooperative function of these neurons. Improved approaches to the neuroanatomical analysis of CNS circuits are thus of great interest. In fact, significant advances in tract-tracing methods have recently been made by using transgenic mice that express transneuronal lectin tracers under the control of neuron-specific promoters. The utility of those animals, however, is limited to the CNS circuit influenced by the particular promoter. Here, we describe a new transgenic mouse that can be used for transneuronal tracing analysis of circuits in any region of the brain or spinal cord. The transgene in these mice results in expression of LacZ in neurons throughout the CNS. Excision of the LacZ gene by Cre-mediated recombination initiates expression of the lectin, wheat germ agglutinin (WGA). To illustrate the diverse uses of these ZW (LacZ-WGA) mice, we triggered WGA expression either by crossing the mice with two Cre-expressing transgenic mouse lines or by microinjecting a Cre-expressing adeno-associated virus into the cerebellum or cerebral cortex. Both approaches resulted in extensive WGA expression in the cell bodies and dendrites of neurons in which the recombination event occurred, as well as anterograde and transneuronal transport of the lectin to second and third order neurons. Because the lectin can be induced in developing and adult animals, and in all regions of the brain and spinal cord, these ZW may prove extremely valuable for numerous studies of CNS circuit analysis. 0027-8424 Journal Article}, Author = {Braz, J. M. and Rico, B. and Basbaum, A. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {beta-Galactosidase/genetics;Neurons/*physiology;Support, Non-U.S. Gov't;Brain/*physiology;Protein Transport;Recombinant Proteins/metabolism;Promoter Regions (Genetics);T pdf;Mice, Transgenic;Support, U.S. Gov't, P.H.S.;Dependovirus/genetics;Wheat Germ Agglutinins/*genetics/metabolism;Mice;Animals;Integrases/*metabolism;23 Technique;Viral Proteins/*metabolism}, Number = {23}, Organization = {Department of Anatomy and Physiology and W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco 94143, USA.}, Pages = {15148-53}, Title = {Transneuronal tracing of diverse CNS circuits by Cre-mediated induction of wheat germ agglutinin in transgenic mice}, Uuid = {5B619A33-A209-4996-A942-F9D6B5355F1E}, Volume = {99}, Year = {2002}, url = {papers/Braz_ProcNatlAcadSciUSA2002.pdf}} @article{Brazelton:2000, Abstract = {After intravascular delivery of genetically marked adult mouse bone marrow into lethally irradiated normal adult hosts, donor-derived cells expressing neuronal proteins (neuronal phenotypes) developed in the central nervous system. Flow cytometry revealed a population of donor-derived cells in the brain with characteristics distinct from bone marrow. Confocal microscopy of individual cells showed that hundreds of marrow-derived cells in brain sections expressed gene products typical of neurons (NeuN, 200-kilodalton neurofilament, and class III beta-tubulin) and were able to activate the transcription factor cAMP response element-binding protein (CREB). The generation of neuronal phenotypes in the adult brain 1 to 6 months after an adult bone marrow transplant demonstrates a remarkable plasticity of adult tissues with potential clinical applications.}, Author = {Brazelton, T. R. and Rossi, F. M. and Keshet, G. I. and Blau, H. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Cell Differentiation;Animals;Phosphorylation;Bone Marrow Transplantation;Microscopy, Confocal;Phenotype;Brain;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Male;Olfactory Bulb;Bone Marrow Cells;DNA-Binding Protein, Cyclic AMP-Responsive;Research Support, U.S. Gov't, P.H.S.;Cell Size;Neurons;Flow Cytometry;Mice;Luminescent Proteins;Biological Markers;Gene Expression;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {20553649}, Month = {12}, Nlm_Id = {0404511}, Number = {5497}, Organization = {Department of Molecular Pharmacology, CCSR 4215, 269 Campus Drive, Stanford University, Stanford, CA 94305-5175, USA.}, Pages = {1775-9}, Pii = {9028}, Pubmed = {11099418}, Title = {From marrow to brain: expression of neuronal phenotypes in adult mice}, Uuid = {20DD63EE-E9D5-11DA-920C-000D9346EC2A}, Volume = {290}, Year = {2000}, url = {papers/Brazelton_Science2000.pdf}} @article{Brecht:2007, Abstract = {Neural networks of the rodent barrel cortex are particularly tractable for developing a quantitative understanding of response transformations in a cortical column. A column in barrel cortex consists of approximately 10 compartments. Two thalamic input pathways, a sensory lemniscal one and sensorimotor paralemniscal one, are transformed to approximately 7 population outputs, each with distinct spatiotemporal response characteristics. Granular and supragranular layers are sites of segregated processing in lemniscal and paralemniscal pathways, whereas infragranular layers are sites of intracolumnar, lemniscal/paralemniscal integration. Individual thalamocortical connections are relatively weak, and a considerable fraction of thalamocortical afferents contributes to each sensory response. Intracortically, relatively few but strong synaptic connections contribute to sensory responses, and responses are rapidly terminated by inhibition. Overall cortical population activity is very low. Whiskers mediate a wide range of behaviors and many natural tactile behaviors occur very rapidly. Vibrissal object recognition can be size invariant and motion invariant and is based on the tactile 'Gestaltwahrnehmung' of shape.}, Author = {Brecht, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008;review}, Month = {8}, Nlm_Id = {9111376}, Number = {4}, Organization = {Bernstein Center for Computational Neuroscience, Humboldt University Berlin, Philippstr. 13 House 6, 10115 Berlin, Germany. michael.brecht\@bccn-berlin.de}, Pages = {408-16}, Pii = {S0959-4388(07)00091-8}, Pubmed = {17702566}, Title = {Barrel cortex and whisker-mediated behaviors}, Uuid = {4B33F412-7F3A-4F7F-8DC9-86D6B38F82BA}, Volume = {17}, Year = {2007}, url = {papers/Brecht_CurrOpinNeurobiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2007.07.008}} @article{Bregman:2002, Abstract = {Earlier studies suggested that while after spinal cord lesions and transplants at birth, the transplants serve both as a bridge and as a relay to restore supraspinal input caudal to the injury (Bregman, 1994), after injury in the adult the spinal cord transplants serve as a relay, but not as a bridge. We show here, that after complete spinal cord transection in adult rats, delayed spinal cord transplants and exogenous neurotrophic factors, the transplants can also serve as a bridge to restore supraspinal input (Fig. 9). We demonstrate here that when the delivery of transplants and neurotrophins are delayed until 2 weeks after spinal cord transection, the amount of axonal growth and the amount of recovery of function are dramatically increased. Under these conditions, both supraspinal and propriospinal projections to the host spinal cord caudal to the transection are reestablished. The growth of supraspinal axons across the transplant and back into the host spinal cord caudal to the lesion was dependent upon the presence of exogenous neurotrophic support. Without the neurotrophins, only propriospinal axons were able to re-establish connections across the transplant. Studies using peripheral nerve or Schwann cell grafts have shown that some anatomical connectivity can be restored across the injury site, particularly under the influence of neurotrophins (Xu et al., 1995a,b; Cheng et al., 1996; Ye and Houle, 1997). Without neurotrophin treatment, brainstem axons do not enter [figure: see text] the graft (Xu et al., 1995a,b; Cheng et al., 1996; Ye and Houle, 1997). Similarly, cells genetically modified to secrete neurotrophins and transplanted into the spinal cord influence the axonal growth of specific populations of spinally projecting neurons (Tuszynski et al., 1996, 1997; Grill et al., 1997; Blesch and Tuszynski, 1997). Taken together, these studies support a role for neurotrophic factors in the repair of the mature CNS. The regrowth of supraspinal and propriospinal input across the transection site was associated with consistent improvements in hindlimb locomotor function. Animals performed alternating and reciprocal hindlimb stepping with plantar foot contact to the treadmill or stair during ascension. Furthermore, they acquired hindlimb weight support and demonstrated appropriate postural control for balance and equilibrium of all four limbs. After spinal cord injury in the adult, the circuitry underlying rhythmic alternating stepping movements is still present within the spinal cord caudal to the lesion, but is now devoid of supraspinal control. We show here that restoring even relatively small amounts of input allows supraspinal neurons to access the spinal cord circuitry. Removing the re-established supraspinal input after recovery (by retransection rostral to the transplant) abolished the recovery and abolished the serotonergic fibers within the transplant and spinal cord caudal to the transplant. This suggests that at least some of the recovery observed is due to re-establishing supraspinal input across the transplant, rather than a diffuse influence of the transplant on motor recovery. It is unlikely, however, that the greater recovery of function in animals that received delayed transplant and neurotrophins is due solely to the restoration of supraspinal input. Recent work by Ribotta et al. (2000) suggests that segmental plasticity within the spinal cord contributes to weight support and bilateral foot placement after spinal cord transection. This recovery of function occurs after transplants of fetal raphe cells into the adult spinal cord transected at T11. Recovery of function appears to require innervation of the L1-L2 segments with serotonergic fibers, and importantly, animals require external stimulation (tail pinch) to elicit the behavior. In the current study, animals with transection only did not develop stepping overground or on the treadmill without tail pinch, although the transplant and neurotrophin-treated groups did so without external stimuli. Therefore both reorganization of the segmental circuitry and partial restoration of supraspinal input presumably interact to yield the improvements in motor function observed. It is unlikely that the recovery of skilled forelimb movement observed can be mediated solely by reorganization of segmental spinal cord circuitry. We suggest that the restoration of supraspinal input contributes to the recovery observed. It is likely that after CNS injury, reorganization occurs both within the spinal cord and at supraspinal levels, and together contribute to the recovery of automatic and skilled forelimb function and of locomotion. In summary, the therapeutic intervention of tissue transplantation and exogenous neurotrophin support leads to improvements in supraspinal and propriospinal input across the transplant into the host caudal cord and a concomitant improvement in locomotor function. Paradoxically, delaying these interventions for several weeks after a spinal cord transection leads to dramatic improvements in recovery of function and a concomitant restoration of supraspinal input into the host caudal spinal cord. These findings suggest that opportunity for intervention after spinal cord injury may be far greater than originally envisioned, and that CNS neurons with long-standing injuries may be able to re-initiate growth leading to improvement in motor function.}, Author = {Bregman, Barbara S. and Coumans, Jean-Valery V. and Dai, Hai Ning and Kuhn, Penelope L. and Lynskey, James and McAtee, Marietta and Sandhu, Faheem}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0079-6123}, Journal = {Prog Brain Res}, Keywords = {Axons;Research Support, Non-U.S. Gov't;Neuroprotective Agents;Cell Transplantation;Nerve Regeneration;Spinal Cord Injuries;Neuronal Plasticity;Mammals;Research Support, U.S. Gov't, P.H.S.;Forelimb;Locomotion;Animals;24 Pubmed search results 2008;Neurons;review}, Medline = {22328364}, Nlm_Id = {0376441}, Organization = {Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20007, USA. bregmanb\@georgetown.edu}, Pages = {257-73}, Pubmed = {12440372}, Title = {Transplants and neurotrophic factors increase regeneration and recovery of function after spinal cord injury}, Uuid = {30EF16BD-52DD-46D7-AEE7-341B5FCC8679}, Volume = {137}, Year = {2002}} @article{Brenowitz:2003, Abstract = {Many types of neurons release endocannabinoids from their dendrites in response to elevation of intracellular calcium levels. Endocannabinoids then activate presynaptic cannabinoid receptors, thereby inhibiting neurotransmitter release for tens of seconds. A crucial step in understanding the physiological role of this retrograde signaling is to determine its sensitivity to elevations of postsynaptic calcium. Here we determine and compare the calcium dependence of endocannabinoid-mediated retrograde inhibition at three types of synapses onto cerebellar Purkinje cells. Previous studies have shown that Purkinje cell depolarization results in endocannabinoid-mediated retrograde inhibition of synapses received from climbing fibers, granule cell parallel fibers, and inhibitory interneurons. Using several calcium indicators with a range of affinities, we performed a series of in situ and in vitro calibrations to quantify calcium levels in Purkinje cells. We found that postsynaptic calcium levels of approximately 15 microM are required for half-maximal retrograde inhibition at all of these synapses. In contrast, previous studies had suggested that endocannabinoid release could occur with slight elevations of calcium above resting levels, which implies that inhibition should be widespread and continuously modulated by subtle changes in intracellular calcium levels. However, our results indicate that such small changes in intracellular calcium are not sufficient to evoke endocannabinoid release. Instead, because of its high requirement for calcium, retrograde inhibition mediated by calcium-dependent endocannabinoid release from Purkinje cells will occur under more restricted conditions and with greater spatial localization than previously appreciated.}, Author = {Brenowitz, Stephan D. and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Electric Stimulation;Purkinje Cells;Synapses;Calcium Signaling;Rats;Animals;research support, u.s. gov't, p.h.s. ;Patch-Clamp Techniques;Rats, Sprague-Dawley;in vitro ;Endocannabinoids;Calcium;Fatty Acids, Unsaturated;21 Neurophysiology;Cerebellum;24 Pubmed search results 2008;Neural Inhibition;Excitatory Postsynaptic Potentials}, Month = {7}, Nlm_Id = {8102140}, Number = {15}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {6373-84}, Pii = {23/15/6373}, Pubmed = {12867523}, Title = {Calcium dependence of retrograde inhibition by endocannabinoids at synapses onto Purkinje cells}, Uuid = {B7A412DC-315E-403F-980B-8E368F034562}, Volume = {23}, Year = {2003}, url = {papers/Brenowitz_JNeurosci2003.pdf}} @article{Brenowitz:2006, Abstract = {Endocannabinoids can act as retrograde messengers that allow postsynaptic cells to regulate the strength of their synaptic inputs. In the cerebellum, Purkinje cells (PCs) release endocannabinoids through two mechanisms. Synaptic activation evokes local endocannabinoid release that relies on a pathway that involves the metabotropic glutamate receptor mGluR1 and phospholipase-C (PLC). In contrast, depolarization evokes endocannabinoid release from the entire dendritic arbor. This leads to depolarization-induced suppression of inhibitory (DSI) and excitatory (DSE) synapses by a mechanism that does not involve mGluR1 or PLC. This latter mechanism of endocannabinoid release has only been observed under artificial conditions that transiently elevate postsynaptic calcium to >5 microm. Here, we tested the possibility that this mechanism could lead to retrograde inhibition in response to more realistic calcium signals. At both climbing fiber and inhibitory synapses onto PCs, we found that prolonging the elevation of calcium significantly lowered the peak calcium required to evoke PLC-independent endocannabinoid release. This suggests that the mechanism of endocannabinoid release involved in DSI and DSE is likely to evoke endocannabinoid release in response to physiologically relevant levels of calcium. When dendritic calcium was elevated to 0.4-1 microm for 15 s or more, endocannabinoid release from PCs selectively suppressed inhibitory synapses. This suggests that inhibitory synapses are more sensitive to prolonged calcium increases. Thus, in contrast to localized retrograde inhibition evoked by synaptic activation, modest but sustained calcium elevation could globally suppress inhibitory synapses onto PCs.}, Author = {Brenowitz, Stephan D. and Best, Aaron R. and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;research support, n.i.h., extramural ;Electric Stimulation;Purkinje Cells;Synapses;Animals;Rats;Enzyme Inhibitors;Patch-Clamp Techniques;Rats, Sprague-Dawley;in vitro ;comparative study ;Endocannabinoids;Calcium;Time Factors;Dendrites;Quinoxalines;21 Neurophysiology;Membrane Potentials;Cerebellum;Pyrazoles;24 Pubmed search results 2008;Neural Inhibition;Dose-Response Relationship, Radiation;Piperidines}, Month = {6}, Nlm_Id = {8102140}, Number = {25}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {6841-50}, Pii = {26/25/6841}, Pubmed = {16793891}, Title = {Sustained elevation of dendritic calcium evokes widespread endocannabinoid release and suppression of synapses onto cerebellar Purkinje cells}, Uuid = {D826445C-925C-4E5A-BD73-839C5A7B749F}, Volume = {26}, Year = {2006}, url = {papers/Brenowitz_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1280-06.2006}} @article{Bressoud:1999, Abstract = {The corpus callosum interconnects both corresponding (homotopic) and noncorresponding (heterotopic) cortical sites of the two hemispheres. We have studied the axons that establish heterotopic connections from visual areas 17 and 18 (E axons) by using anterogradely transported biocytin and three-dimensional serial reconstructions in adult cats and in kittens. Their site of termination distinguished four types of axons. Type EI ends near the border between areas 19/21a or 7, and type EII near the PMLS/PLLS border (posteromedial and posterolateral lateral suprasylvian areas). Type EIII and EIV terminate the first near the PMLS/PLLS and PMLS/21a borders, and the second near the PMLS/PLLS and 19/21a or 7 borders. Taking into account the previously studied homotopic axons (O axons; Houzel et al. [1994] Eur. J. Neurosci. 6:898-917), it can be concluded that areas 17 and 18 are interhemispherically connected by at least five types of axons, three of which (O, EI, and EII) terminate near one areal border, the other two (types EIII and EIV), near two areal borders. All types terminate near representations of the vertical meridian of the visual field. The different types of axons can be identified already during the first postnatal week; at this age, unlike in the adult, they originate not only near the 17/18 border, but also, transiently, in area 17. This suggests that the developing cortex contains sets of neurons destined to send their axon to different targets; however, the axons grow beyond their sites of adult termination. Indeed, exuberant growth takes place at the stage of axonal elongation, and at subsequent stages of axonal differentiation, i.e., during subcortical branching, intracortical branching and synaptogenesis. The growth is progressively more constrained in its topographic distribution and the axons are subsequently reshaped by regressive events.}, Author = {Bressoud, R. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Aging;Visual Cortex;Cats;Anatomy, Artistic;Not relevant;Growth Cones;11 Glia;Animals, Newborn;Support, Non-U.S. Gov't;Visual Pathways;Animals;Axons}, Medline = {99198993}, Month = {3}, Nlm_Id = {0406041}, Number = {1}, Organization = {Institute of Cell Biology and Morphology, University of Lausanne, Switzerland.}, Pages = {87-108}, Pii = {10.1002/(SICI)1096-9861(19990329)406:1<87::AID-CNE6>3.0.CO;2-S}, Pubmed = {10100894}, Title = {Typology, early differentiation, and exuberant growth of a set of cortical axons}, Uuid = {DFE00AC9-39CD-4B59-A6D6-0F84F05204F1}, Volume = {406}, Year = {1999}} @article{Breunig:2007, Author = {Breunig, Joshua J. and Arellano, Jon I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Organogenesis;01 Adult neurogenesis general;Cell Fusion;Cell Communication;Neocortex;Microglia;comment;Green Fluorescent Proteins;Animals;24 Pubmed search results 2008;review;Neurons}, Month = {2}, Nlm_Id = {8102140}, Number = {7}, Organization = {Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, Sterling Hall of Medicine C300, P.O. Box 208001, New Haven, CT 06520, USA. joshua.breunig\@yale.edu}, Pages = {1507-8}, Pubmed = {17304702}, Title = {Glowing green pyramids: a false positive for neocortical neurogenesis reveals a novel neuronal-microglial fusion in the postnatal brain}, Uuid = {4A76BE6B-12E3-43AD-859D-42A23A62C45B}, Volume = {27}, Year = {2007}, url = {papers/Breunig_JNeurosci2007.pdf}} @article{Brewer:1999, Abstract = {Adult mammalian CNS neurons appear to be terminally differentiated and postmitotic. However, this conclusion may be due to nonpermissive conditions in the brain or in culture media. If embryonic rat hippocampal neurons are cultured in Neurobasal/B27 with FGF2, nearly all neurons proliferated until a maximum density was reached. Similarly, adult neurons can be cultured that fire action potentials and display immunoreactivity for neurofilament, MAP2, tau, and glutamate. Seventy percent of the 3000 isolated adult cells per milligram of brain tissue began to proliferate after 3 days in culture and incorporated BrdU. By 4 days of regeneration in culture, virtually all neuron-like cells with asymmetric processes were glutamate positive and immunoreactive for neurofilament. Immunoreactivity of the intermediate filament stem cell marker nestin increased in adult cells to levels present in freshly isolated embryonic neurons. These are the first studies to demonstrate that over 50\%of adult CNS cells with neuron-like characteristics retain regenerative and proliferative potential.}, Author = {Brewer, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Fetus;Animals;Cells, Cultured;Rats;Fluorescent Antibody Technique;Glutamic Acid;Rats, Sprague-Dawley;Hippocampus;Neurofilament Proteins;Antimetabolites;Fibroblast Growth Factor 2;Nerve Regeneration;Antibodies;Research Support, U.S. Gov't, P.H.S.;Intermediate Filament Proteins;Neurons;Age Factors;Cell Division;24 Pubmed search results 2008;Bromodeoxyuridine;Culture Media;Stem Cells;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {99417615}, Month = {9}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Medical Microbiology and Immunology, Southern Illinois University School of Medicine, Springfield, Illinois, 62794-9626, USA.}, Pages = {237-47}, Pii = {S0014488699971236}, Pubmed = {10486191}, Title = {Regeneration and proliferation of embryonic and adult rat hippocampal neurons in culture}, Uuid = {FC745F52-BE49-4EE2-ACEA-7E52DF4C526E}, Volume = {159}, Year = {1999}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.1999.7123}} @article{Brewer:1993, Abstract = {We have systematically optimized the concentrations of 20 components of a previously published serum-free medium (Brewer and Cotman, Brain Res 494: 65-74, 1989) for survival of rat embryonic hippocampal neurons after 4 days in culture. This serum-free medium supplement, B27, produced neuron survival above 60\%, independent of plating density above 160 plated cells/mm2. For isolated cells (< 100 cells/mm2), survival at 4 days was still above 45\%, but could be rescued to the 60\%level at 40 cells/mm2 by simply applying a coverslip on top of the cells. This suggests a need for additional trophic factors. High survival was achieved with osmolarity lower than found in Dulbecco's Modified Eagle's Medium (DMEM), and by reducing cysteine and glutamine concentrations and by the elimination of toxic ferrous sulphate found in DME/F12. Neurobasal is a new medium that incorporates these modifications to DMEM. In B27/Neurobasal, glial growth is reduced to less than 0.5\%of the nearly pure neuronal population, as judged by immunocytochemistry for glial fibrillary acidic protein and neuron-specific enolase. Excellent long-term viability is achieved after 4 weeks in culture with greater than 90\%viability for cells plated at 640/mm2 and greater than 50\%viability for cells plated at 160/mm2. Since the medium also supports the growth of neurons from embryonic rat striatum, substantia nigra, septum, and cortex, and neonatal dentate gyrus and cerebellum (Brewer, in preparation), support for other neuron types is likely. B27/Neurobasal should be useful for in vitro studies of neuronal toxicology, pharmacology, electrophysiology, gene expression, development, and effects of growth factors and hormones.}, Author = {Brewer, G. J. and Torricelli, J. R. and Evege, E. K. and Price, P. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Embryo;Rats, Sprague-Dawley;Neuroglia;Culture Media, Serum-Free;Kinetics;Rats;Culture Media, Conditioned;Hippocampus;Time Factors;Cell Division;Asparagine;Glial Fibrillary Acidic Protein;Cell Survival;Animals;Cells, Cultured;23 Technique;Neurons}, Medline = {93389779}, Month = {8}, Nlm_Id = {7600111}, Number = {5}, Organization = {Southern Illinois University School of Medicine, Springfield 62794.}, Pages = {567-76}, Pubmed = {8377226}, Title = {Optimized survival of hippocampal neurons in B27-supplemented Neurobasal, a new serum-free medium combination}, Uuid = {8FA42730-F0CF-11DA-83A9-000D9346EC2A}, Volume = {35}, Year = {1993}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.490350513}} @article{Briellmann:2006, Abstract = {Double cortex is a neuronal migration disorder, associated with impaired cognitive function and seizures, and characterized by a subcortical band of neurons. Using functional MRI, we assessed the involvement of the subcortical band in language function and with interictal discharges. In both girls assessed, language-associated activation was in typical cortical areas, as well as in parts of the subcortical band. Interictal discharges were associated with deactivation in the subcortical band. This suggests involvement of the subcortical neurons in physiologic and pathologic functions.}, Author = {Briellmann, R. S. and Little, T. and Harvey, A. S. and Abbott, D. F. and Jacobs, R. and Waites, A. B. and Jackson, G. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1526-632X}, Journal = {Neurology}, Keywords = {21 Dysplasia-heterotopia;21 Neurophysiology;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {0401060}, Number = {6}, Organization = {Brain Research Institute, Neurosciences Building, Austin Health, Heidelberg Heights, Victoria 3081, Australia.}, Pages = {1090-3}, Pii = {67/6/1090}, Pubmed = {17000988}, Title = {Pathologic and physiologic function in the subcortical band of double cortex}, Uuid = {1AE40BC2-78E9-4D81-BE93-DD3E9E836B36}, Volume = {67}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1212/01.wnl.0000237554.39283.6b}} @article{Briggman:2006, Abstract = {By using multi-electrode arrays or optical imaging, investigators can now record from many individual neurons in various parts of nervous systems simultaneously while an animal performs sensory, motor or cognitive tasks. Given the large multidimensional datasets that are now routinely generated, it is often not obvious how to find meaningful results within the data. The analysis of neuronal-population recordings typically involves two steps: the extraction of relevant dynamics from neural data, and then use of the dynamics to classify and discriminate features of a stimulus or behavior. We focus on the application of techniques that emphasize interactions among the recorded neurons rather than using just the correlations between individual neurons and a perception or a behavior. An understanding of modern analysis techniques is crucially important for researchers interested in the co-varying activity among populations of neurons or even brain regions.}, Author = {Briggman, Kevin L. and Abarbanel, Henry D. I. and Kristan, William B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Nonlinear Dynamics;Signal Processing, Computer-Assisted;Movement;21 Neurophysiology;Neurophysiology;Action Potentials;Neural Pathways;Research Support, N.I.H., Extramural;Research Support, U.S. Gov't, Non-P.H.S.;Synaptic Transmission;Cognition;Animals;Humans;24 Pubmed search results 2008;review;Neurons}, Month = {4}, Nlm_Id = {9111376}, Number = {2}, Organization = {Max Planck Institute for Medical Research, Department of Biomedical Optics, Jahnstrasse 29, Heidelberg 69120, Germany.}, Pages = {135-44}, Pii = {S0959-4388(06)00039-0}, Pubmed = {16564165}, Title = {From crawling to cognition: analyzing the dynamical interactions among populations of neurons}, Uuid = {121F087E-DC46-4F94-8413-3F9B9FD6EA51}, Volume = {16}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2006.03.014}} @article{Briggman:2005, Abstract = {We investigated decision-making in the leech nervous system by stimulating identical sensory inputs that sometimes elicit crawling and other times swimming. Neuronal populations were monitored with voltage-sensitive dyes after each stimulus. By quantifying the discrimination time of each neuron, we found single neurons that discriminate before the two behaviors are evident. We used principal component analysis and linear discriminant analysis to find populations of neurons that discriminated earlier than any single neuron. The analysis highlighted the neuron cell 208. Hyperpolarizing cell 208 during a stimulus biases the leech to swim; depolarizing it biases the leech to crawl or to delay swimming.}, Author = {Briggman, K. L. and Abarbanel, H. D. I. and Kristan, W. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Coloring Agents;Swimming;Electric Stimulation;Animals;Research Support, U.S. Gov't, Non-P.H.S.;Leeches;Principal Component Analysis;Locomotion;Analysis of Variance;Research Support, U.S. Gov't, P.H.S.;Decision Making;21 Neurophysiology;Neurons;Ganglia, Invertebrate;Discriminant Analysis;Motor Neurons;Membrane Potentials;Interneurons;Microelectrodes;Central Nervous System;Fluorescence Resonance Energy Transfer;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Month = {2}, Nlm_Id = {0404511}, Number = {5711}, Organization = {Division of Biological Sciences, University of California-San Diego, La Jolla, CA 92093-0357, USA.}, Pages = {896-901}, Pii = {307/5711/896}, Pubmed = {15705844}, Title = {Optical imaging of neuronal populations during decision-making}, Uuid = {B06A78D3-2356-4480-BEB4-87968BDF97A8}, Volume = {307}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1103736}} @article{Brill:2008, Abstract = {Distinct olfactory bulb (OB) interneurons are thought to become specified depending on from which of the different subregions lining the lateral ventricle wall they originate, but the role of region-specific transcription factors (TFs) in the generation of OB interneurons diversity is still poorly understood. Despite the crucial roles of the Dlx family of TFs for patterning and neurogenesis in the ventral telencephalon during embryonic development, their role in adult neurogenesis has not yet been addressed. Here we show that in the adult brain, Dlx 1 and Dlx2 are expressed in progenitors of the lateral but not the dorsal subependymal zone (SEZ), thus exhibiting a striking regional specificity. Using retroviral vectors to examine the function of Dlx2 in a cell-autonomous manner, we demonstrate that this TF is necessary for neurogenesis of virtually all OB interneurons arising from the lateral SEZ. Beyond its function in generic neurogenesis, Dlx2 also plays a crucial role in neuronal subtype specification in the OB, promoting specification of adult-born periglomerular neurons (PGNs) toward a dopaminergic fate. Strikingly, Dlx2 requires interaction with Pax6, because Pax6 deletion blocks Dlx2-mediated PGN specification. Thus, Dlx2 wields a dual function by first instructing generic neurogenesis from adult precursors and subsequently specifying PGN subtypes in conjunction with Pax6.}, Author = {Brill, Monika S. and Snapyan, Marina and Wohlfrom, Hilde and Ninkovic, Jovica and Jawerka, Melanie and Mastick, Grant S. and Ashery-Padan, Ruth and Saghatelyan, Armen and Berninger, Benedikt and G{\"o}tz, Magdalena}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Pregnancy;Cell Differentiation;Paired Box Transcription Factors;Animals;Cells, Cultured;Humans;comparative study;Transcription Factors;Female;Homeodomain Proteins;Eye Proteins;Mice, Inbred C57BL;research support, non-u.s. gov't;Olfactory Bulb;Cell Lineage;Neurons;Age Factors;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Repressor Proteins;Transcription, Genetic}, Month = {6}, Nlm_Id = {8102140}, Number = {25}, Organization = {Department of Physiological Genomics, Institute of Physiology, Ludwig-Maximilians University Munich, D-80336 Munich, Germany.}, Pages = {6439-52}, Pii = {28/25/6439}, Pubmed = {18562615}, Title = {A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb}, Uuid = {C8856377-ADBB-4681-B5D9-04E7CB582507}, Volume = {28}, Year = {2008}, url = {papers/Brill_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0700-08.2008}} @article{Brinon:1999, Abstract = {The distribution patterns of four calcium-binding proteins (CaBPs)- calbindin D-28k (CB), calretinin (CR), neurocalcin (NC), and parvalbumin (PV)-in the rat main olfactory bulb were compared, and the degrees ofcolocalization of NC with the other CaBPs were determined by using double immunocytochemical techniques. All investigated CaBPs were detected in groups of periglomerular cells and Van Gehuchten cells, whereas other cell types expressed some of the investigated proteins but not all four. Double-labeling techniques demonstrated the colocalization of NC with CB, CR, or PV in periglomerular cells, whereas each neurochemical group constituted entirely segregated populations in the remaining neuronal types. This is evident in granule cells that demonstrated large but segregated populations immunoreactive to either NC or CR. This study provides a further biochemical characterization of interneuronal types in the rat main olfactory bulb. On the basis of the distinct calcium-binding affinities, each neurochemically defined population may have different responses to calcium influx that would result in the existence of distinct functional subgroups within morphologically defined neuronal types. The expression of the investigated CaBPs in periglomerular cells with both single and colocalized patterns suggests that the local circuits in the glomerular layer are constituted by a complex network of elements with particular calcium requirements.}, Author = {Brinon, J. G. and Martinez-Guijarro, F. J. and Bravo, I. G. and Arevalo, R. and Crespo, C. and Okazaki, K. and Hidaka, H. and Aijon, J. and Alonso, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Comp Neurol}, Keywords = {I;Nerve Tissue Proteins/*metabolism;Immunohistochemistry;Calcium-Binding Proteins/*metabolism;Rats, Wistar;Tissue Distribution/physiology;Animal;Calcium-Binding Protein, Vitamin D-Dependent/metabolism;Rats/*metabolism;Neurons/metabolism;Support, Non-U.S. Gov't;Male;Parvalbumins/metabolism;Olfactory Bulb/cytology/*metabolism;13 Olfactory bulb anatomy}, Number = {3}, Organization = {Departamento de Biologia Celular y Patologia, Universidad de Salamanca, Spain.}, Pages = {404-14.}, Title = {Coexpression of neurocalcin with other calcium-binding proteins in the rat main olfactory bulb}, Uuid = {52C72484-46FE-4B19-A627-DF054EDF01FC}, Volume = {407}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10320220}} @article{Brionne:2003, Abstract = {TGF-beta1 is a key regulator of diverse biological processes in many tissues and cell types, but its exact function in the developing and adult mammalian CNS is still unknown. We report that lack of TGF-beta1 expression in neonatal Tgfb1(-/-) mice results in a widespread increase in degenerating neurons accompanied by reduced expression of synaptophysin and laminin and a prominent microgliosis. Lack of TGF-beta1 also strongly reduces survival of primary neurons cultured from Tgfb1(-/-) mice. TGF-beta1 deficiency in adult Tgfb1(-/+) mice results in increased neuronal susceptibility to excitotoxic injury, whereas astroglial overexpression of TGF-beta1 protects adult mice against neurodegeneration in acute, excitotoxic and chronic injury paradigms. This study reveals a nonredundant function for TGF-beta1 in maintaining neuronal integrity and survival of CNS neurons and in regulating microglial activation. Because individual TGF-beta1 expression levels in the brain vary considerably between humans, this finding could have important implications for susceptibility to neurodegeneration.}, Author = {Brionne, Thomas C. and Tesseur, Ina and Masliah, Eliezer and Wyss-Coray, Tony}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Mice, Transgenic;Cell Survival;Mice, Inbred BALB C;Comparative Study;Gliosis;Mice, Inbred C57BL;Not relevant;11 Glia;Microglia;Cell Death;Transforming Growth Factor beta;Support, U.S. Gov't, P.H.S.;Animals;Brain;Mice;Neurons;Cells, Cultured}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.}, Pages = {1133-45}, Pii = {S0896627303007669}, Pubmed = {14687548}, Title = {Loss of TGF-beta 1 leads to increased neuronal cell death and microgliosis in mouse brain}, Uuid = {17617A48-818E-4D48-B28C-5752F29172ED}, Volume = {40}, Year = {2003}} @article{Britanova:2006, Abstract = {Projection neurons of the developing cerebral cortex are generated in the cerebral ventricular zone and subsequently move to the developing cortical plate via radial migration. Conversely, most inhibitory interneurons originate in the ganglionic eminences and enter the developing cortical plate by tangential migration. Using immunohistochemical analysis together with tracer labeling experiments in organotypic brain slices, we show that a portion of cortical projection neurons migrates tangentially over long distances. Lineage analysis revealed that these neurons are derived from Emx1+ cortical progenitors and express the transcription factor Satb2 but do not express GABA or Olig1. In vitro and in vivo analysis of reeler mutant brains demonstrated that although reeler mutation does not influence tangential migration of interneurons, it affects the tangential migration of cortical projection neurons.}, Author = {Britanova, and Alifragis, and Junek, and Jones, and Gruss, and Tarabykin,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0372762}, Organization = {Department of Molecular Biology of Neuronal Signals, Max-Plank-Institute for Experimental Medicine, 37075 G{\"o}ttingen, Germany; Laboratory of Molecular Technologies, Shemiakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16/10, 117871 Moscow, Russia.}, Pii = {S0012-1606(06)00964-X}, Pubmed = {16901480}, Title = {A novel mode of tangential migration of cortical projection neurons}, Uuid = {0E6B1D9F-1547-4526-B23A-E0FAB448EA8D}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2006.06.040}} @article{Britanova:2008, Abstract = {Pyramidal neurons of the neocortex can be subdivided into two major groups: deep- (DL) and upper-layer (UL) neurons. Here we report that the expression of the AT-rich DNA-binding protein Satb2 defines two subclasses of UL neurons: UL1 (Satb2 positive) and UL2 (Satb2 negative). In the absence of Satb2, UL1 neurons lose their identity and activate DL- and UL2-specific genetic programs. UL1 neurons in Satb2 mutants fail to migrate to superficial layers and do not contribute to the corpus callosum but to the corticospinal tract, which is normally populated by DL axons. Ctip2, a gene required for the formation of the corticospinal tract, is ectopically expressed in all UL1 neurons in the absence of Satb2. Satb2 protein interacts with the Ctip2 genomic region and controls chromatin remodeling at this locus. Satb2 therefore is required for the initiation of the UL1-specific genetic program and for the inactivation of DL- and UL2-specific genes.}, Author = {Britanova, Olga and de Juan Romero, Camino and Cheung, Amanda and Kwan, Kenneth Y. and Schwark, Manuela and Gyorgy, Andrea and Vogel, Tanja and Akopov, Sergey and Mitkovski, Miso and Agoston, Denes and Sestan, Nenad and Moln{\'a}r, Zolt{\'a}n and Tarabykin, Victor}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Max-Planck-Institute for Experimental Medicine, Hermann-Rein Strasse 3, 37075 G{\"o}ttingen, Germany; Shemiakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16 / 10, 117871 Moscow, Russia.}, Pages = {378-92}, Pii = {S0896-6273(08)00033-0}, Pubmed = {18255031}, Title = {Satb2 is a postmitotic determinant for upper-layer neuron specification in the neocortex}, Uuid = {FD82BD13-9494-469D-85CE-CC4BD6577418}, Volume = {57}, Year = {2008}, url = {papers/Britanova_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.12.028}} @article{Britz:2006, Abstract = {We showed previously that the proneural genes Neurogenin1 (Ngn1) and Ngn2 are required to specify the phenotypes of early- and not late-born neurons in the neocortex, acting in part through repression of Mash1, a third cortically expressed proneural gene. The precise timing of Ngn1/2 specification activity was unexpected given these genes are expressed throughout cortical development, prompting us to search for a later function. Here we reveal that Ngn2 and Mash1 are expressed in a dynamic fashion, acquiring a cell cycle-biased, nonoverlapping distribution, with preferential expression in prospective basal progenitors, during mid corticogenesis. We also identified a new function for Ngn2 during this latter period, demonstrating that it is required to regulate the transit of cortical progenitors from the ventricular zone (VZ) to the subventricular zone. Notably, Ngn2 regulates progenitor maturation at least in part through repression of Mash1 as misexpression of Mash1 strongly enhanced progenitor cell exit from the VZ. Significantly, the ability of Mash1 to promote progenitor cell maturation occurred independently of its ability to respecify cortical cells and is thus a novel function for Mash1. Taken together, these data support a model whereby Ngn2 and Mash1 function together to regulate the zonal distribution of progenitors in the developing neocortex.}, Author = {Britz, Olivier and Mattar, Pierre and Nguyen, Laurent and Langevin, Lisa-Marie M. and Zimmer, C{\'e}line and Alam, Sharmila and Guillemot, Fran\c{c}ois and Schuurmans, Carol}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Animals;Aging;Cell Differentiation;Research Support, Non-U.S. Gov't;Neurons;Cells, Cultured;24 Pubmed search results 2008;Basic Helix-Loop-Helix Transcription Factors;Nerve Tissue Proteins;Stem Cells;In Vitro;Cell Aggregation;Male;Cell Movement;Mice;Cerebral Cortex;Organogenesis}, Month = {7}, Nlm_Id = {9110718}, Organization = {Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.}, Pages = {i138-51}, Pii = {16/suppl_1/i138}, Pubmed = {16766700}, Title = {A role for proneural genes in the maturation of cortical progenitor cells}, Uuid = {67FDB250-8AC2-4895-A535-3777F7F63663}, Volume = {16 Suppl 1}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhj168}} @article{Broadwell:1993, Abstract = {Extracellular pathways circumventing the mammalian blood-brain fluid barriers (e.g., blood-brain and blood-CSF barriers) have been investigated in the rat by immunohistochemical localization of the endogenous serum proteins albumin, IgG, complement C-9, and IgM and by the exogenous tracer protein horseradish peroxidase (HRP). A demonstrable extracellular pathway into the central nervous system (CNS) is evident at the level of the subarachnoid space/pial surface. Immunoreaction products for the serum proteins and reaction product of intravenously administered HRP are identified over the entire pial surface, in the Virchow-Robin spaces and subpial cortical grey matter, and within phagocytes occupying the subarachnoid space/pial surface and perivascular clefts throughout the CNS. From specific circumventricular organs (e.g., median eminence, area postrema, subfornical organ), well known to lie outside the blood-brain barrier (BBB), each of the blood-borne proteins readily enters adjacent white and grey matter and the ventricular system for subsequent rostrocaudal labeling of the ependymal cell lining. Similar immunohistochemical and blood-borne HRP results are obtained in the CNS of the neonatal rat. Peroxidase delivered into the aorta of postmortem adult rats confirms the presence of a BBB in brain sites containing blood vessels impermeable to blood-borne HRP and the absence of a BBB in sites revealed as leaky to blood-borne HRP in the live rat. The results suggest blood-borne macromolecules, including those of the immune and complement systems, have potential widespread, extracellular distribution within the CNS and cerebrospinal fluid from sites deficient in a BBB (e.g., subarachnoid space/pial surface, circumventricular organs). These observations may have important clinical implications regarding experimental and pathologic autoimmune dysfunction within the CNS and impact on the interpretation of potential transcytosis of blood-borne peptides and proteins through the cerebral endothelium in vivo. A summary diagram of suspected extracellular and intracellular pathways circumventing the blood-brain fluid barriers is provided.}, Author = {Broadwell, R. D. and Sofroniew, M. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Immunoglobulin M;Animals;Models, Cardiovascular;Humans;Blood Proteins;Rats;Immunoglobulin G;Serum Albumin;Brain;Female;Extracellular Space;Rats, Wistar;Complement 9;11 Glia;Cerebrovascular Circulation;Rats, Inbred WF;Blood-Brain Barrier;Male;Animals, Newborn;Research Support, U.S. Gov't, P.H.S.;Neurons;Horseradish Peroxidase;Artifacts;Immunohistochemistry;Microscopy, Electron;Models, Neurological;Research Support, Non-U.S. Gov't}, Medline = {93259273}, Month = {4}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Surgery, University of Maryland School of Medicine, Baltimore 21201.}, Pages = {245-63}, Pii = {S0014488683710599}, Pubmed = {8491281}, Title = {Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system}, Uuid = {91116093-779F-4B3F-B875-669A9DC56C53}, Volume = {120}, Year = {1993}} @article{Broccardo:2006, Abstract = {The notion that the ATP-binding cassette transporter-A2 (ABCA2) may be involved in brain sterol homeostasis and is associated with early onset Alzheimer's disease led us to explore its neural expression. Our data support and extend the previous reports on ABCA2 expression by oligodendrocytes. They evidence that ABCA2 (i) is located in intracellular vesicles, identified in transfected cells as lysosome-related organelles only partially overlapping with classical endolysosomes; (ii) is a marker of neural progenitors as it is expressed in the subventricular zone of the lateral ventricle and the dentate gyrus of the hippocampal formation, sites of continual neurogenesis in the adult brain, and in nestin(+) cells differentiated in vitro from embryonic stem cells; (iii) persists, in the adult rodent brain, in a subset of GABAergic and glutamatergic neurons. Considering that the latter are targets of Alzheimer's lesions, these data provide a new rationale to explore the neuropathological consequences of ABCA2 functional dysregulations.}, Author = {Broccardo, and Nieoullon, and Amin, and Masmejean, and Carta, and Tassi, and Pophillat, and Rubartelli, and Pierres, and Rougon, and Nieoullon, and Chazal, and Chimini,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {2985190R}, Organization = {Centre d'Immunologie de Marseille Luminy INSERM CNRS, Universit{\'e} de la M{\'e}diterran{\'e}e Marseille, France.}, Pii = {JNC3714}, Pubmed = {16539677}, Title = {ABCA2 is a marker of neural progenitors and neuronal subsets in the adult rodent brain}, Uuid = {E396159E-C1ED-4E5C-A4D3-A7905F147129}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1471-4159.2006.03714.x}} @article{Brody:1998, Abstract = {Slow covariations in neuronal resting potentials can lead to artefactually fast cross-correlations in their spike trains. J. Neurophysiol. 80: 3345-3351, 1998. A model of two lateral geniculate nucleus (LGN) cells, which interact only through slow (tens of seconds) covariations in their resting membrane potentials, is used here to investigate the effect of such covariations on cross-correlograms taken during stimulus-driven conditions. Despite the slow timescale of the interactions, the model generates cross-correlograms with peak widths in the range of 25-200 ms. These bear a striking resemblance to those reported in studies of LGN cells by Sillito et al., which were taken at the time as evidence of a fast spike timing synchronization interaction; the model highlights the possibility that those correlogram peaks may have been caused by a mechanism other than spike synchronization. Slow resting potential covariations are suggested instead as the dominant generating mechanism. How can a slow interaction generate covariogram peaks with a width 100-1,000 times thinner than its timescale? Broad peaks caused by slow interactions are modulated by the cells' poststimulus time histograms (PSTHs). When the PSTHs have thin peaks (e.g., tens of milliseconds), the cross-correlogram peaks generated by slow interactions will also be thin; such peaks are easily misinterpretable as being caused by fast interactions. Although this point is explored here in the context of LGN recordings, it is a general point and applies elsewhere. When cross-correlogram peak widths are of the same order of magnitude as PSTH peak widths, experiments designed to reveal short-timescale interactions must be interpreted with the issue of possible contributions from slower interactions in mind.}, Author = {Brody, C. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Electric Stimulation;Synapses;21 Epilepsy;Excitatory Postsynaptic Potentials;21 Neurophysiology;Geniculate Bodies;Models, Neurological;Calcium Channels;Electrophysiology;Membrane Potentials;Neurons;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {0375404}, Number = {6}, Organization = {Instituto de Fisiolog{\'\i}a Celular, Universidad Nacional Aut{\'o}noma de M{\'e}xico, C.P. 04510 M{\'e}xico D.F., Mexico.}, Pages = {3345-51}, Pubmed = {9862930}, Title = {Slow covariations in neuronal resting potentials can lead to artefactually fast cross-correlations in their spike trains}, Uuid = {EECB50A3-E1FC-471D-B50F-42AFE0BF0AE5}, Volume = {80}, Year = {1998}, url = {papers/Brody_JNeurophysiol1998.pdf}} @article{Brooks:2002, Abstract = {As one part of a distinguished scientific career, Dr. Bryn Bridges focused his attention on the issue of DNA damage and repair in stationary phase bacteria. His work in this area led to his interest in DNA repair and mutagenesis in another non-dividing cell population, the neurons in the mammalian nervous system. He has specifically taken an interest in the magnocellular neurons of the central nervous system, and the possibility that somatic mutations may be occurring in these neurons. As part of this special issue dedicated to Bryn Bridges upon his retirement, I will discuss the various DNA repair pathways known to be active in the nervous system. The importance of DNA repair to the nervous system is most graphically illustrated by the neurological abnormalities observed in patients with hereditary diseases associated with defects in DNA repair. I will consider the mechanisms underlying the neurological abnormalities observed in patients with four of these diseases: xeroderma pigmentosum (XP), Cockayne's syndrome (CS), ataxia telangectasia (AT) and AT-like disorder (ATLD). I will also propose a mechanism for one of the observations indicating that somatic mutation can occur in the magnocellular neurons of the aging rat brain. Finally, as a parallel to Bridges inquiry into how much DNA synthesis is going on in stationary phase bacteria, I will address the question of how much DNA synthesis in going on in neurons, and the implications of the answer to this question for recent studies of neurogenesis in adult mammals. 0027-5107 Journal Article Review Review, Academic}, Author = {Brooks, P. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Mutat Res}, Keywords = {Nervous System Malformations/*etiology;Mutation;Neurons/*physiology;Aging/genetics;EE pdf;Human;Cockayne Syndrome/genetics;08 Aberrant cell cycle;*DNA Repair;Xeroderma Pigmentosum/genetics;Brain/abnormalities/cytology;Ataxia Telangiectasia/genetics;Heredodegenerative Disorders, Nervous System/etiology}, Number = {1-2}, Organization = {Section on Molecular Neurobiology, Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Drive, MSC 8110, Bethesda, MD 20892-8110, USA. pjbrooks\@mail.nih.gov}, Pages = {93-108}, Title = {DNA repair in neural cells: basic science and clinical implications}, Uuid = {6D9D62F3-DC9B-4854-B692-886058B75248}, Volume = {509}, Year = {2002}, url = {papers/Brooks_MutatRes2002}} @article{Brooks-Kayal:2001, Abstract = {Profound alterations in the function of GABA occur over the course of postnatal development. Changes in GABA(A) receptor expression are thought to contribute to these differences in GABAergic function, but how subunit changes correlate with receptor function in individual developing neurons has not been defined precisely. In the current study, we correlate expression of 14 different GABA(A) receptor subunit mRNAs with changes in the pharmacological properties of the receptor in individual hippocampal dentate granule cells over the course of postnatal development in rat. We demonstrate significant developmental differences in GABA(A) receptor subunit mRNA expression, including greater than two-fold lower expression of alpha1-, alpha4- and gamma2- subunit mRNAs and 10-fold higher expression of alpha5-mRNA in immature compared with adult neurons. These differences correlate both with regional changes in subunit protein level and with alterations in GABA(A) receptor function in immature dentate granule cells, including two-fold higher blockade by zinc and three-fold lower augmentation by type-I benzodiazepine site modulators. Further, we find an inverse correlation between changes in GABA(A) receptor zinc sensitivity and abundance of vesicular zinc in dentate gyrus during postnatal development. These findings suggest that developmental differences in subunit expression contribute to alterations in GABA(A) receptor function during postnatal development.}, Author = {Brooks-Kayal, A. R. and Shumate, M. D. and Jin, H. and Rikhter, T. Y. and Kelly, M. E. and Coulter, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurochem}, Keywords = {RNA, Messenger/biosynthesis;13 Olfactory bulb anatomy;Rats;Sedatives, Nonbarbiturate/pharmacology;Patch-Clamp Techniques;Animal;gamma-Aminobutyric Acid/pharmacology;Dentate Gyrus/cytology/*growth &development/metabolism;Dyes;Zinc/pharmacology;I-4;Animals, Newborn;Support, Non-U.S. Gov't;Blotting, Western;Support, U.S. Gov't, P.H.S.;Pyridines/pharmacology;Neurons/metabolism;Receptors, GABA-A/*biosynthesis}, Number = {5}, Organization = {Pediatric Regional Epilepsy Program and Joseph Stokes Research Institute of The Children's Hospital of Philadelphia, PA 19104, USA. kayal\@email.chop.edu}, Pages = {1266-78.}, Title = {gamma-Aminobutyric acid(A) receptor subunit expression predicts functional changes in hippocampal dentate granule cells during postnatal development}, Uuid = {CA95C309-EAC9-4969-9C8E-00562D176A91}, Volume = {77}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11389177%20http://www.jneurochem.org/cgi/content/full/77/5/1266%20http://www.jneurochem.org/cgi/content/abstract/77/5/1266}} @article{Brooks-Kayal:1998, Abstract = {Temporal lobe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplification (aRNA) techniques in single dentate granule cells, we demonstrate that expression of GABA(A) receptor subunit mRNAs is substantially altered in neurons from epileptic rats. These changes in gene expression precede epilepsy onset by weeks and correlate with profound alterations in receptor function, indicating that aberrant GABA(A) receptor expression and function has an essential role in the process of epileptogenesis.}, Author = {Brooks-Kayal, A. R. and Shumate, M. D. and Jin, H. and Rikhter, T. Y. and Coulter, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {Pilocarpine;Electric Conductivity;Gene Expression Regulation;Animals;Rats;Seizures;Cell Separation;21 Epilepsy;Patch-Clamp Techniques;RNA, Messenger;Receptors, GABA-A;Research Support, U.S. Gov't, P.H.S.;Histocytochemistry;Epilepsy, Temporal Lobe;Neurons;21 Neurophysiology;Dentate Gyrus;24 Pubmed search results 2008}, Medline = {98442693}, Month = {10}, Nlm_Id = {9502015}, Number = {10}, Organization = {Joseph Stokes Research Institute of The Children's Hospital of Philadelphia, Department of Neurology, University of Pennsylvania, 19104, USA. kayal\@email.chop.edu}, Pages = {1166-72}, Pubmed = {9771750}, Title = {Selective changes in single cell GABA(A) receptor subunit expression and function in temporal lobe epilepsy}, Uuid = {330B7AF4-45FA-4A7D-AAAD-1C13A6760012}, Volume = {4}, Year = {1998}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/2661}} @article{Brown:1979, Abstract = {Cultured Friend murine erythroleukemia cells (Friend cells) are induced to undergo erythroid differentiation when grown in the presence of dimethylsulfoxide (DMSO) and other compounds. The effects of unifilar substitution of bromouracil (BU) for thymidine in the DNA (BU-DNA) of Friend cells were examined. Cells were grown in the presence of 5-bromodeoxy-uridine (BrdU) for one generation, then centrifuged and resuspended in medium containing DMSO without BrdU. These cells exhibited a delay in the appearance of heme-producing, benzidine-reative (B+) cells and a decreased rate of cell proliferation in comparison to the control not containing BU-DNA. A transient inhibition of entry into S phase was observed when control cells or cells containing BU-DNA were grown in the presence of DMSO) for 10 to 20 hours. This transient inhibition was increased in the BrdU culture. Thus BU-substitution in Friend cells alters other cellular functions in addition to erythroid differentiation. The rate of increase in the percent of cells committed to differentiate (those forming B+ colonies in plasma clots) was similar in the BrdU and control cultures until 40 to 50 hours. After this time, a delay in the appearance of committed cells was observed in the BrdU culture. The effect of BrdU on the appearance of B+ cells was more pronounced and occurred earlier than its effect on the rate of commitment. Therefore, the delay in the appearance of B+ cells in the BrdU culture was due primarily to perturbation of post-commitment events such as the accumulation of hemoglobin. We also examined the effect on growth and differentiation after BrdU was incorporated during different intervals of S phase in cells synchronized by centrifugal elutriation or by double thymidine block and hydroxyurea treatment. The delay in the appearance of B+ cells and inhibition of cell proliferation were only observed when BrdU was incorporated in the first half of S phase. BrdU (10 muM) had no effect on growth or differentiation when present during late S or G1 and G2. These results, using two very different methods to achieve cell synchrony, indicate that the effects of BrdU on growth and differentiation described above are due to its incorporation into DNA sequences replicating during early S.}, Author = {Brown, E. H. and Schildkraut, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0021-9541}, Journal = {J Cell Physiol}, Keywords = {23 Technique;01 Adult neurogenesis general;Cell Differentiation;Research Support, U.S. Gov't, P.H.S.;Cell Division;Leukemia, Experimental;DNA Replication;15 Retrovirus mechanism;Animals;Interphase;Bromodeoxyuridine;Leukemia, Erythroblastic, Acute;24 Pubmed search results 2008}, Medline = {79216625}, Month = {5}, Nlm_Id = {0050222}, Number = {2}, Pages = {261-78}, Pubmed = {287673}, Title = {Perturbation of growth and differentiation of Friend murine erythroleukemia cells by 5-bromodeoxyuridine incorporation in early S phase}, Uuid = {E9E269A5-5129-4317-B241-7233CE046A42}, Volume = {99}, Year = {1979}} @article{Brown:2003a, Abstract = {During development of the central nervous system, expression of the microtubule binding protein doublecortin (DCX) is associated with migration of neuroblasts. In addition to this developmental role, expression of DCX remains high within certain areas of the adult mammalian brain. These areas, mainly the dentate gyrus and the lateral ventricle wall in conjunction with the rostral migratory stream and olfactory bulb, retain the capacity to generate new neurons into adulthood. Adult neurogenesis is typically detected by incorporation of bromodeoxyuridine (BrdU) into dividing cells and colabeling of BrdU-positive cells with markers for mature neurons. To elucidate whether DCX could act as an alternative indicator for adult neurogenesis, we investigated the temporal expression pattern of DCX in neurogenic regions of the adult brain. Analysis of newly generated cells showed that DCX is transiently expressed in proliferating progenitor cells and newly generated neuroblasts. As the newly generated cells began expressing mature neuronal markers, DCX immunoreactivity decreased sharply below the level of detection and remained undetectable thereafter. The transient expression pattern of DCX in neuronal committed progenitor cells/neuroblasts indicates that DCX could be developed into a suitable marker for adult neurogenesis and may provide an alternative to BrdU labeling. This assumption is further supported by our observation that the number of DCX-expressing cells in the dentate gyrus was decreased with age according to the reduction of neurogenesis in the aging dentate gyrus previously reported.}, Author = {Brown, Jason P. and Couillard-Despr{\'e}s, S{\'e}bastien and Cooper-Kuhn, Christiana M. and Winkler, J{\"u}rgen and Aigner, Ludwig and Kuhn, H. Georg}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Electrophoresis, Polyacrylamide Gel;Cell Differentiation;Animals;Microtubule-Associated Proteins;Aging;Rats;Fluorescent Antibody Technique;Mitosis;Female;Cell Movement;02 Adult neurogenesis migration;Hippocampus;Rats, Wistar;Time Factors;Neuropeptides;Olfactory Bulb;Blotting, Western;Neurons;Dentate Gyrus;Central Nervous System;Stem Cells;Bromodeoxyuridine;Lateral Ventricles;Research Support, Non-U.S. Gov't}, Medline = {22935334}, Month = {12}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Neurology, University of Regensburg, 93053 Regensburg, Germany.}, Pages = {1-10}, Pubmed = {14574675}, Title = {Transient expression of doublecortin during adult neurogenesis}, Uuid = {2D30F285-6D12-11DA-A4FE-000D9346EC2A}, Volume = {467}, Year = {2003}, url = {papers/Brown_JCompNeurol2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10874}} @article{Brown:2003, Abstract = {Many types of neurons can release endocannabinoids that act as retrograde signals to inhibit neurotransmitter release from presynaptic terminals. Little is known, however, about the properties or role of such inhibition under physiological conditions. Here we report that brief bursts of presynaptic activity evoked endocannabinoid release, which strongly inhibited parallel fiber-to-Purkinje cell synapses in rat cerebellar slices. This retrograde inhibition was triggered by activation of either postsynaptic metabotropic or ionotropic glutamate receptors and was restricted to synapses activated with high-frequency bursts. Thus, endocannabinoids allow neurons to inhibit specific synaptic inputs in response to a burst, thereby dynamically fine-tuning the properties of synaptic integration.}, Author = {Brown, Solange P. and Brenowitz, Stephan D. and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Excitatory Postsynaptic Potentials;Calcium Channel Blockers;Excitatory Amino Acid Antagonists;Electric Stimulation;Purkinje Cells;Presynaptic Terminals;Calcium Signaling;Rats;Animals;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Naphthalenes;Rats, Sprague-Dawley;Receptors, AMPA;Endocannabinoids;Organ Culture Techniques;Morpholines;Dendrites;21 Neurophysiology;Calcium Channels;Pyrazoles;24 Pubmed search results 2008;Receptors, Metabotropic Glutamate;Neural Inhibition;Piperidines}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.}, Pages = {1048-57}, Pii = {nn1126}, Pubmed = {14502290}, Title = {Brief presynaptic bursts evoke synapse-specific retrograde inhibition mediated by endogenous cannabinoids}, Uuid = {7489BB90-A365-45FB-95D0-BE3517FE1BF9}, Volume = {6}, Year = {2003}, url = {papers/Brown_NatNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1126}} @article{Brown:2004, Abstract = {Multiple electrodes are now a standard tool in neuroscience research that make it possible to study the simultaneous activity of several neurons in a given brain region or across different regions. The data from multi-electrode studies present important analysis challenges that must be resolved for optimal use of these neurophysiological measurements to answer questions about how the brain works. Here we review statistical methods for the analysis of multiple neural spike-train data and discuss future challenges for methodology research.}, Author = {Brown, Emery N. and Kass, Robert E. and Mitra, Partha P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Neurons;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Action Potentials;Statistics;Models, Neurological;Time Factors;Brain Mapping;Electrophysiology;Nerve Net;Animals;Humans;24 Pubmed search results 2008;review;Art}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Neuroscience Statistics Research Laboratory, Department of Anesthesia and Critical Care, Massachusetts General Hospital, and Division of Health Sciences and Technology, Harvard Medical School, Boston, 02114, USA. brown\@neurostat.mgh.harvard.edu}, Pages = {456-61}, Pii = {nn1228}, Pubmed = {15114358}, Title = {Multiple neural spike train data analysis: state-of-the-art and future challenges}, Uuid = {39CB4BA5-0B02-48A7-98C8-4FEDD753ABE8}, Volume = {7}, Year = {2004}, url = {papers/Brown_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1228}} @article{Bruccoleri:2000, Abstract = {The osteopetrotic (op/op) mouse, deficient in biologically active colony stimulating factor 1 (CSF-1), was used to examine the role of microglia in chemical-induced trauma. Op/op mice and normal phenotype littermates (non-op/op) received an acute i.p. injection of the hippocampal toxicant, trimethyltin hydroxide (TMT; 1.5 or 2.0 mg/kg). At 2.0 mg/kg, both mice displayed severe degeneration of dentate granule neurons. At 1.5 mg/kg, non-op/op mice showed a limited punctate pattern of neuronal death while op/op mice showed prominent neuronal death. TMT-induced astrocyte reactivity was similar in both groups. RNase protection assays were conducted on hippocampal tissue at 24 hr post-TMT. Elevations were seen in mRNA levels for the host response genes: intercellular cell adhesion molecule (ICAM-1; non-op/op 80\%, op/op 85\%), the protease inhibitor EB22 (non-op/op 60\%, op/op 300\%), and glial fibrillary acidic protein (GFAP; non-op/op 300\%, op/op 480\%) within 24 hr. Macrophage-1 antigen (Mac-1) mRNA levels were lower in all op/op mice and were not induced by TMT exposure. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta mRNA levels were elevated in non-op/op mice while mRNA levels for interferon inducible protein (IP-10) and monocyte chemoattractant protein (MCP-1) were elevated in op/op mice. Tumor necrosis factor alpha (TNFalpha) mRNA levels were significantly elevated in both non-op/op (100\%) and op/op (600\%) mice. TNFbeta mRNA levels in op/op mice were elevated 200\%and interleukin 1alpha (IL-1alpha) 150\%. Reverse transcriptase polymerase chain reaction (RT-PCR) showed a TMT-induced elevation in INFalpha and INFbeta mRNA levels and no elevation of INFgamma. mRNA levels of the CSF-1 receptor, c-fms, were unaltered.}, Author = {Bruccoleri, A. and Harry, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cytokines;Dose-Response Relationship, Drug;Tumor Necrosis Factor;Animals;Astrocytes;Osteopetrosis;Intercellular Adhesion Molecule-1;Mice, Mutant Strains;Cell Survival;Receptor, Macrophage Colony-Stimulating Factor;Trimethyltin Compounds;Female;Microglia;Lymphotoxin;Hippocampus;RNA, Messenger;11 Glia;Male;Reverse Transcriptase Polymerase Chain Reaction;Ribonucleases;Chemokines, CXC;Neurons;Interleukin-1;Neurodegenerative Diseases;Mice;Monocyte Chemoattractant Protein-1;Glial Fibrillary Acidic Protein}, Medline = {20459227}, Month = {10}, Nlm_Id = {7600111}, Number = {1}, Organization = {Neurotoxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.}, Pages = {146-55}, Pii = {10.1002/1097-4547(20001001)62:1<146::AID-JNR15>3.0.CO;2-L}, Pubmed = {11002296}, Title = {Chemical-induced hippocampal neurodegeneration and elevations in TNFalpha, TNFbeta, IL-1alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice}, Uuid = {3FDFF91B-4807-4558-8B55-C39CC230736F}, Volume = {62}, Year = {2000}} @article{Brumberg:2003, Abstract = {Layer VI is the origin of the massive feedback connection from the cortex to the thalamus, yet its complement of cell types and their connections is poorly understood. The physiological and morphological properties of corticofugal neurons of layer VI of mouse primary visual cortex were investigated in slices loaded with the Ca(2+) indicator fura-2AM. To identify corticofugal neurons, electrical stimulation of the white matter (WM) was done in conjunction with calcium imaging to detect neurons that responded with changes in intracellular Ca(2+) concentrations in response to the stimulation. Subsequent whole cell recordings confirmed that they discharged antidromic action potentials after WM stimulation. Antidromically activated neurons were more excitable and had different spiking properties than neighboring nonantidromic neurons, although both groups had similar input resistances. Furthermore, antidromic neurons possessed narrower action potentials and smaller afterhyperpolarizations. Additionally, three-dimensional reconstructions indicated that antidromically activated neurons had a distinct morphology with longer apical dendrites and fewer nonprimary dendrites than nonantidromic cells. To identify the antidromic neurons, rhodamine microspheres were injected into the dorsal lateral geniculate nucleus of the thalamus and allowed to retrogradely transport back to the somata of the layer VI cortico-geniculate neurons. Physiological and anatomical analysis indicated that most antidromic neurons were likely to be cortico-geniculate neurons. Our results show that cortico-thalamic neurons represent a specific functional and morphological class of layer VI neurons.}, Author = {Brumberg, Joshua C. and Hamzei-Sichani, Farid and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Rhodamines;Electric Stimulation;Electrophysiology;Synapses;Animals;Image Processing, Computer-Assisted;Neural Pathways;research support, u.s. gov't, p.h.s. ;Patch-Clamp Techniques;Female;in vitro ;Mice, Inbred C57BL;Calcium;Male;21 Calcium imaging;Microspheres;Thalamus;Action Potentials;21 Neurophysiology;Neurons;Membrane Potentials;Mice;24 Pubmed search results 2008;Microelectrodes;Visual Cortex}, Month = {5}, Nlm_Id = {0375404}, Number = {5}, Organization = {Department of Biological Sciences, Columbia University, New York, New York 10027, USA. joshua\_brumberg\@qc.edu}, Pages = {2854-67}, Pii = {89/5/2854}, Pubmed = {12740416}, Title = {Morphological and physiological characterization of layer VI corticofugal neurons of mouse primary visual cortex}, Uuid = {FF9130F1-F47E-4C83-9D49-C2278C522B6A}, Volume = {89}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01051.2002}} @article{Brummelkamp:2002, Abstract = {Mammalian genetic approaches to study gene function have been hampered by the lack of tools to generate stable loss-of-function phenotypes efficiently. We report here a new vector system, named pSUPER, which directs the synthesis of small interfering RNAs (siRNAs) in mammalian cells. We show that siRNA expression mediated by this vector causes efficient and specific down-regulation of gene expression, resulting in functional inactivation of the targeted genes. Stable expression of siRNAs using this vector mediates persistent suppression of gene expression, allowing the analysis of loss-of-function phenotypes that develop over longer periods of time. Therefore, the pSUPER vector constitutes a new and powerful system to analyze gene function in a variety of mammalian cell types. 1095-9203 Journal Article}, Author = {Brummelkamp, T. R. and Bernards, R. and Agami, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Science}, Keywords = {RNA, Untranslated/chemistry/*genetics/metabolism;Human;Transfection;Phenotype;Mutation;23 Technique;Genes, p53;RNA, Small Interfering;Nucleic Acid Conformation;RNA, Messenger/chemistry/*genetics/metabolism;*Gene Silencing;Support, Non-U.S. Gov't;Ligases/genetics;Tumor Cells, Cultured;T abstr;Protein Kinases/genetics/metabolism;Down-Regulation;*Ubiquitin-Protein Ligase Complexes;Protein p53/metabolism;*Genetic Techniques;*Genetic Vectors}, Number = {5567}, Organization = {Division of Molecular Carcinogenesis, Division of Tumor Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, Netherlands.}, Pages = {550-3}, Pubmed = {11910072}, Title = {A system for stable expression of short interfering RNAs in mammalian cells}, Uuid = {E29548BF-8B2D-4094-95A9-A2A9034DD07A}, Volume = {296}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11910072}} @article{Brunelli:1996, Author = {Brunelli, S. and Faiella, A. and Capra, V. and Nigro, V. and Simeone, A. and Cama, A. and Boncinelli, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {10 Development;Transcription Factors;Magnetic Resonance Imaging;Humans;Base Sequence;Brain;Female;Homeodomain Proteins;Tomography, X-Ray Computed;research support, non-u.s. gov't;Brain Diseases;Point Mutation;Male;DNA Primers;10 genetics malformation;Genes, Homeobox;Pedigree;Polymorphism, Single-Stranded Conformational;24 Pubmed search results 2008;Molecular Sequence Data;Nerve Tissue Proteins}, Month = {1}, Nlm_Id = {9216904}, Number = {1}, Organization = {DIBIT, Istituto Scientifico HS Raffaele, Milan, Italy.}, Pages = {94-6}, Pubmed = {8528262}, Title = {Germline mutations in the homeobox gene EMX2 in patients with severe schizencephaly}, Uuid = {98D61E40-7680-4E3B-96BC-3746145630DA}, Volume = {12}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ng0196-94}} @article{Brunet:2007, Abstract = {Homeogenes encode homeoprotein transcription factors that have fundamental roles in development. They are key players in genetic networks that lay out the body plan and also determine morphology and physiology at the cellular and multicellular level. However, homeoproteins share activities that extend beyond transcription, including translation regulation and signalling. For example, homeoproteins participate in the definition of territories in the neuroepithelium and also have a function in axonal guidance. Based on these examples, we propose that homeoproteins are not only morphogenetic transcription factors, but also morphogens themselves.}, Author = {Brunet, Isabelle and Di Nardo, Ariel A. and Sonnier, Laure and Beurdeley, Marine and Prochiantz, Alain}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Neurons;Transcription Factors;24 Pubmed search results 2008;Central Nervous System;Morphogenesis;Animals;Humans;Homeodomain Proteins;review;Axons}, Month = {6}, Nlm_Id = {7808616}, Number = {6}, Organization = {Unit{\'e} Mixte de Recherche 8542, Development and Evolution of the Nervous System (Development and Neuropharmacology Group), Ecole normale sup{\'e}rieure, 46 rue d'Ulm, 75005 Paris, France.}, Pages = {260-7}, Pii = {S0166-2236(07)00075-6}, Pubmed = {17418905}, Title = {The topological role of homeoproteins in the developing central nervous system}, Uuid = {5E1B6B83-E759-4A6D-BA92-8F66734C1861}, Volume = {30}, Year = {2007}, url = {papers/Brunet_TrendsNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2007.03.010}} @article{Brussel:2004, Abstract = {The integrated form of human immunodeficiency virus type 1 (HIV-1) DNA is classically considered to be the sole template for viral gene expression. However, several studies have suggested that unintegrated viral DNA species could also support transcription. To determine the contribution of the different species of HIV-1 DNA to viral expression, we first monitored intracellular levels of various HIV-1 DNA and RNA species in a single-round infection assay. We observed that, in comparison to the precocity of HIV-1 DNA synthesis, viral expression was delayed, suggesting that only the HIV-1 DNA species that persist for a sufficient period of time would be transcribed efficiently. We next evaluated the transcriptional activity of the circular forms of HIV-1 DNA bearing two long terminal repeats, since these episomes were reported to exhibit an intrinsic molecular stability. Our results support the notion that these circular species of HIV-1 DNA are naturally transcribed during HIV-1 infection, thereby participating in virus replication.}, Author = {Brussel, Audrey and Sonigo, Pierre}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Research Support, Non-U.S. Gov't;DNA, Circular;HIV-1;Cell Line;Gene Expression;DNA, Viral;Transcription, Genetic;RNA, Viral;HIV Integrase;Humans;HIV Long Terminal Repeat;15 Retrovirus mechanism;24 Pubmed search results 2008;Virus Integration}, Month = {10}, Nlm_Id = {0113724}, Number = {20}, Organization = {D{\'e}partement des Maladies Infectieuses, Institut Cochin, INSERM U567, CNRS UMR 8104, Universit{\'e} Ren{\'e} Descartes, 22 rue M{\'e}chain, 75014 Paris, France.}, Pages = {11263-71}, Pii = {78/20/11263}, Pubmed = {15452245}, Title = {Evidence for gene expression by unintegrated human immunodeficiency virus type 1 DNA species}, Uuid = {B12A0D8F-3EE8-49FD-AFC2-15F723FB16D4}, Volume = {78}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.78.20.11263-11271.2004}} @article{Brustle:1995, Abstract = {The stereotyped positions occupied by individual classes of neurons are a fundamental characteristic of CNS cytoarchitecture. To study the regulation of neuronal positioning, we injected genetically labeled neural precursors derived from dorsal and ventral mouse forebrain into the telencephalic vesicles of embryonic rats. Cells from both areas were found to participate in the generation of telencephalic, diencephalic, and mesencephalic brain regions. Donor-derived neurons populated the host brain in distinct patterns and acquired phenotypic features appropriate for their final location. These observations indicate that neuronal migration and differentiation are predominantly regulated by non-cell-autonomous signals. Exploiting this phenomenon, intrauterine transplantation allows generation of controlled chimerism in the mammalian brain.}, Author = {Brustle, O. and Maskos, U. and McKay, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuron}, Keywords = {02 Adult neurogenesis migration;Cell Differentiation;Transplantation, Heterologous;Rats, Sprague-Dawley;Brain/cytology/*embryology;Rats;Embryo/cytology/*physiology;Mice, Inbred C57BL;Animal;Neurons/cytology/physiology/*transplantation;B abstr;Stem Cells/cytology/physiology/transplantation;Support, Non-U.S. Gov't;Mice;Cell Movement}, Number = {6}, Organization = {Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892-4092, USA.}, Pages = {1275-85.}, Title = {Host-guided migration allows targeted introduction of neurons into the embryonic brain}, Uuid = {270994A3-2101-40F7-9ACD-E59296800DC4}, Volume = {15}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8845152}} @article{Bucci:1999, Abstract = {The thalamic connectivity and basal forebrain cholinergic input to the posterior parietal cortex (PPC) of Long-Evans rats was examined using combined retrograde tracing and immunocytochemical methods. As in previous studies, the PPC could be distinguished by its input from the lateral posterior, lateral dorsal, and posterior nuclei of the thalamus, but not the lateral geniculate nucleus or ventrobasal complex. These nuclei were also observed to receive reciprocal projections from the ipsilateral PPC. Cholinergic neurons innervating the PPC were primarily localized to the substantia innominata/nucleus basalis region. The implications of these data for possible functions of the cholinergic input to PPC are discussed.}, Author = {Bucci, D. J. and Conley, M. and Gallagher, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Molecular Probes;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Thalamic Nuclei;Rats, Long-Evans;Rats;Research Support, U.S. Gov't, P.H.S.;Neural Pathways;Choline O-Acetyltransferase;Parietal Lobe;Prosencephalon;Animals;Male;24 Pubmed search results 2008;Neurons;Frontal Lobe}, Medline = {99253381}, Month = {4}, Nlm_Id = {9100935}, Number = {5}, Organization = {Curriculum in Neurobiology, University of North Carolina at Chapel Hill 27599, USA.}, Pages = {941-5}, Pubmed = {10321464}, Title = {Thalamic and basal forebrain cholinergic connections of the rat posterior parietal cortex}, Uuid = {17331C21-62CB-4F24-BFF7-51A4FAAC526B}, Volume = {10}, Year = {1999}} @article{Buchkremer-Ratzmann:1998, Abstract = {Seizures are one of the most frequent complications after cerebral ischemia in patients. Up to now it is unknown which mechanisms are responsible for this. As shown previously photothrombotic infarction in rat neocortex leads to a sweeping suppression of GABAergic inhibition. In this study we investigated whether and to what extent epileptiform discharges can be observed in this ischemia model. In neocortical slices from lesioned animals we did not find spontaneous epileptic activity or paroxysmal depolarisation shifts. However, ipsi- and contralateral to a photothrombotic lesion the frequency of double and multiple discharges was markedly increased when compared to unlesioned controls. Surprisingly, neither the drug lubeluzole which was has been shown to prevent the GABAergic disinhibition observed after photothrombotic lesioning of rat neocortex, nor the prevention of spreading depressions by the NMDA-receptor antagonist MK-801 during lesion induction significantly affected the frequency of epileptiform discharges. This indicates that the epileptiform discharges are probably caused by functional alterations of glutamatergic receptors.}, Author = {Buchkremer-Ratzmann, I. and August, M. and Hagemann, G. and Witte, O. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0022-510X}, Journal = {J Neurol Sci}, Keywords = {Electric Stimulation;Intracranial Embolism and Thrombosis;In Vitro;Electrophysiology;Rats;Animals;Dizocilpine Maleate;21 Epilepsy;Neuroprotective Agents;Neocortex;Epilepsy;Reaction Time;Rats, Wistar;Thiazoles;Cerebral Infarction;Male;21 Neurophysiology;Light;24 Pubmed search results 2008;Piperidines}, Medline = {98248261}, Month = {4}, Nlm_Id = {0375403}, Number = {2}, Organization = {Neurologische Klinik, Heinrich-Heine-Universit{\"a}t, D{\"u}sseldorf, Germany.}, Pages = {133-7}, Pii = {S0022510X98000343}, Pubmed = {9588847}, Title = {Epileptiform discharges to extracellular stimuli in rat neocortical slices after photothrombotic infarction}, Uuid = {6DAD6465-F67A-4AE4-B2A2-6FCAFAC70510}, Volume = {156}, Year = {1998}} @article{Buck:2000, Author = {Buck, L. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cell}, Keywords = {Odors;I;Smell/*physiology;Protein Structure, Tertiary;Gene Expression/physiology;Receptors, Odorant/*chemistry/*genetics;Mammals;Animal;Pheromones/*chemistry/*physiology;13 Olfactory bulb anatomy}, Number = {6}, Organization = {Howard Hughes Medical Institute, Neurobiology Department, Harvard Medical School, Boston, Massachusetts 02115, USA. lbuck\@hms.harvard.edu}, Pages = {611-8.}, Title = {The molecular architecture of odor and pheromone sensing in mammals}, Uuid = {B5C0C278-DD53-4442-8AA7-0805D73A0F3F}, Volume = {100}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10761927}} @article{Buck:2004, Author = {Buck, Linda B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Receptors, Odorant;13 Olfactory bulb anatomy;Smell;History, 20th Century;Olfactory Receptor Neurons;Autobiography;historical article;Molecular Biology;comment;biography;Mice;Animals;24 Pubmed search results 2008;Humans;History, 21st Century}, Medline = {23227458}, Month = {1}, Nlm_Id = {0413066}, Number = {2 Suppl}, Organization = {Howard Hughes Medical Institute, Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, Washington 98109, USA. lbuck\@fhcrc.org}, Pages = {S117-9, 1 p following S119}, Pubmed = {15055598}, Title = {The search for odorant receptors}, Uuid = {D085A76C-6FB8-4AB1-90F6-597460534F70}, Volume = {116}, Year = {2004}} @article{Budd:2000, Abstract = {In cultured cerebrocortical neurons, mild excitotoxic insults or staurosporine result in apoptosis. We show here that N-methyl-d- aspartate (NMDA) receptor-mediated, but not staurosporine-mediated, apoptosis is preceded by depolarization of the mitochondrial membrane potential (Deltapsi(m)) and ATP loss. Both insults, however, release cytochrome c (Cyt c) into the cytoplasm. What prompts mitochondria to release Cyt c and the mechanism of release are as yet unknown. We examined the effect of inhibition of the adenine nucleotide translocator (ANT), a putative component of the mitochondrial permeability transition pore. Inhibition of the mitochondrial ANT with bongkrekic acid (BA) prevented NMDA receptor-mediated apoptosis of cerebrocortical neurons. Concomitantly, BA prevented Deltapsi(m) depolarization, promoted recovery of cellular ATP content, and blocked caspase-3 activation. However, in the presence of BA, Cyt c was still released. Because BA prevented NMDA-induced caspase-3 activation and apoptosis, the presence of Cyt c in the neuronal cytoplasm is not sufficient for the induction of caspase activity or apoptosis. In contrast to these findings, BA was ineffective in preventing staurosporine-induced activation of caspases or apoptosis. Additionally, staurosporine-induced, but not NMDA-induced, apoptosis was associated with activation of caspase-8. These results indicate that, in cerebrocortical cultures, excessive NMDA receptor activation precipitates neuronal apoptosis by means of mitochondrial dysfunction, whereas staurosporine utilizes a distinct pathway.}, Author = {Budd, S. L. and Tenneti, L. and Lishnak, T. and Lipton, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Caspases/metabolism;Cerebral Cortex/*cytology;Staurosporine/pharmacology;Nerve Tissue Proteins/antagonists &inhibitors/physiology;Adenine Nucleotide Translocase/antagonists &inhibitors/physiology;Bongkrekic Acid/pharmacology;07 Excitotoxicity Apoptosis;Apoptosis/drug effects/*physiology;Cytochrome c/physiology;Animal;Protein Kinases/antagonists &inhibitors;Adenosine Triphosphate/metabolism;Enzyme Activation/drug effects;E-10;Enzyme Inhibitors/pharmacology;Receptors, N-Methyl-D-Aspartate/physiology;Support, Non-U.S. Gov't;Mitochondria/enzymology/*physiology;Support, U.S. Gov't, P.H.S.;Intracellular Membranes/metabolism;Permeability;Neurons/*cytology/drug effects}, Number = {11}, Organization = {Center for Neuroscience and Aging Research, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.}, Pages = {6161-6.}, Title = {Mitochondrial and extramitochondrial apoptotic signaling pathways in cerebrocortical neurons}, Uuid = {C0F9BA2F-AF1D-4C0B-8B9A-8295AB68E8DA}, Volume = {97}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10811898}} @article{Buehlmann:2008, Abstract = {Extensive theoretical and experimental work on the neuronal correlates of visual attention raises two hypotheses about the underlying mechanisms. The first hypothesis, named biased competition, originates from experimental single-cell recordings that have shown that attention upmodulates the firing rates of the neurons encoding the attended features and downregulates the firing rates of the neurons encoding the unattended features. Furthermore, attentional modulation of firing rates increases along the visual pathway. The other, newer hypothesis assigns synchronization a crucial role in the attentional process. It stems from experiments that have shown that attention modulates gamma-frequency synchronization. In this paper, we study the coexistence of the two phenomena using a theoretical framework. We find that the two effects can vary independently of each other and across layers. Therefore, the two phenomena are not concomitant. However, we show that there is an advantage in the processing of information if rate modulation is accompanied by gamma modulation, namely that reaction times are shorter, implying behavioral relevance for gamma synchronization.}, Author = {Buehlmann, Andres and Deco, Gustavo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Bias (Epidemiology);Attention;Photic Stimulation;Animals;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Cortical Synchronization;Visual Perception;Visual Pathways;Excitatory Amino Acid Agonists;research support, non-u.s. gov't;Time Factors;Visual Fields;Action Potentials;Haplorhini;N-Methylaspartate;Neurons;Inhibition (Psychology);24 Pubmed search results 2008;Visual Cortex;Spectrum Analysis;Models, Neurological}, Month = {7}, Nlm_Id = {8102140}, Number = {30}, Organization = {Computational Neuroscience, Universitat Pompeu Fabra, 08003 Barcelona, Spain. andres.buhlmann\@upf.edu}, Pages = {7679-86}, Pii = {28/30/7679}, Pubmed = {18650344}, Title = {The neuronal basis of attention: rate versus synchronization modulation}, Uuid = {4D5BBE08-C462-46D7-AD20-4B3425BF6B33}, Volume = {28}, Year = {2008}, url = {papers/Buehlmann_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5640-07.2008}} @article{Buffelli:2003, Abstract = {Synaptic activity drives synaptic rearrangement in the vertebrate nervous system; indeed, this appears to be a main way in which experience shapes neural connectivity. One rearrangement that occurs in many parts of the nervous system during early postnatal life is a competitive process called 'synapse elimination'. At the neuromuscular junction, where synapse elimination has been analysed in detail, muscle fibres are initially innervated by multiple axons, then all but one are withdrawn and the 'winner' enlarges. In support of the idea that synapse elimination is activity dependent, it is slowed or speeded when total neuromuscular activity is decreased or increased, respectively. However, most hypotheses about synaptic rearrangement postulate that change depends less on total activity than on the relative activity of the competitors. Intuitively, it seems that the input best able to excite its postsynaptic target would be most likely to win the competition, but some theories and results make other predictions. Here we use a genetic method to selectively inhibit neurotransmission from one of two inputs to a single target cell. We show that more powerful inputs are strongly favoured competitors during synapse elimination.}, Author = {Buffelli, Mario and Burgess, Robert W. and Feng, Guoping and Lobe, Corrinne G. and Lichtman, Jeff W. and Sanes, Joshua R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {10 Development;Animals;Synapses;Neuronal Plasticity;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Axons;Mice, Transgenic;Gene Deletion;Mice, Inbred C57BL;Choline O-Acetyltransferase;10 circuit formation;Neuromuscular Junction;Mice, Knockout;21 Neurophysiology;research support, u.s. gov't, p.h.s.;Muscle, Skeletal;21 Activity-development;Motor Neurons;Mice;24 Pubmed search results 2008;Models, Neurological;Transgenes}, Month = {7}, Nlm_Id = {0410462}, Number = {6947}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid, St Louis, Missouri 63110, USA.}, Pages = {430-4}, Pii = {nature01844}, Pubmed = {12879071}, Title = {Genetic evidence that relative synaptic efficacy biases the outcome of synaptic competition}, Uuid = {2899ED06-52BC-4828-9F4F-DB0726D95264}, Volume = {424}, Year = {2003}, url = {papers/Buffelli_Nature2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01844}} @article{Bulfone:2005, Abstract = {The vertebrate telencephalon is composed of many architectonically and functionally distinct areas and structures, with billions of neurons that are precisely connected. This complexity is fine-tuned during development by numerous genes. To identify genes involved in the regulation of telencephalic development, a specific subset of differentially expressed genes was characterized. Here, we describe a set of cDNAs encoded by genes preferentially expressed during development of the mouse telencephalon that was identified through a functional genomics approach. Of 832 distinct transcripts found, 223 (27\%) are known genes. Of the remaining, 228 (27\%) correspond to expressed sequence tags of unknown function, 58 (7\%) are homologs or orthologs of known genes, and 323 (39\%) correspond to novel rare transcripts, including 48 (14\%) new putative noncoding RNAs. As an example of this latter group of novel precursor transcripts of micro-RNAs, telencephalic embryonic subtractive sequence (TESS) 24.E3 was functionally characterized, and one of its targets was identified: the zinc finger transcription factor ZFP9. The TESS transcriptome has been annotated, mapped for chromosome loci, and arrayed for its gene expression profiles during neural development and differentiation (in Neuro2a and neural stem cells). Within this collection, 188 genes were also characterized on embryonic and postnatal tissue by in situ hybridization, demonstrating that most are specifically expressed in the embryonic CNS. The full information has been organized into a searchable database linked to other genomic resources, allowing easy access to those who are interested in the dissection of the molecular basis of telencephalic development.}, Author = {Bulfone, Alessandro and Carotenuto, Pietro and Faedo, Andrea and Aglio, Veruska and Garzia, Livia and Bello, Anna Maria and Basile, Andrea and Andr\`{e}, Alessandra and Cocchia, Massimo and Guardiola, Ombretta and Ballabio, Andrea and Rubenstein, John L. R. and Zollo, Massimo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-13 09:45:17 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;MicroRNAs; microRNAs; development}, Month = {8}, Nlm_Id = {8102140}, Number = {33}, Organization = {Stem Cell Research Institute-Hospital San Raffaele, Istituto Scientifico San Raffaele, 20132 Milan, Italy. bulfone.alessandro\@hsr.it}, Pages = {7586-600}, Pii = {25/33/7586}, Pubmed = {16107646}, Title = {Telencephalic embryonic subtractive sequences: a unique collection of neurodevelopmental genes}, Uuid = {22B5E9A9-A103-4318-9BBF-EFF41456ABB9}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0522-05.2005}} @article{Bureau:2004, Abstract = {Sensory cortex is ordered into columns, each tuned to a subset of peripheral stimuli. To identify the principles underlying the construction of columnar architecture, we monitored the development of circuits in the rat barrel cortex, using laser-scanning photostimulation analysis of synaptic connectivity, reconstructions of axonal arbors, and in vivo whole-cell recording. Circuits impinging onto layer 2/3 neurons from layers 4 and 2/3 developed in a monotonic, precise progression, with little evidence for transient hyperinnervation at the level of cortical columns. Consistent with this, synaptic currents measured in layer 2/3 neurons at PND 8, just after these neurons ceased to migrate, revealed already spatially well-tuned receptive fields.}, Author = {Bureau, Ingrid and Shepherd, Gordon M. G. and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't ;Vibrissae;24 Pubmed search results 2008;Reaction Time;Nerve Net;10 Development;Animals;Photic Stimulation;Age Factors;comparative study ;In Vitro;Electric Stimulation;Brain Mapping;Synapses;21 Circuit structure-function;Dendrites;Neocortex;Membrane Potentials;Axons;Comparative Study;Rats, Sprague-Dawley;Lasers;Action Potentials;Rats;Patch-Clamp Techniques;Animals, Newborn;21 Neurophysiology;18 Classic Neuroanatomy Physiology;Support, Non-U.S. Gov't;Neurons;in vitro}, Month = {6}, Nlm_Id = {8809320}, Number = {5}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.}, Pages = {789-801}, Pii = {S0896627304002910}, Pubmed = {15182718}, Title = {Precise development of functional and anatomical columns in the neocortex}, Uuid = {617F37D0-6584-4BFA-9964-E8D87CF24805}, Volume = {42}, Year = {2004}, url = {papers/Bureau_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.05.002}} @article{Bureau:2006, Abstract = {Primary sensory cortical areas receive information through multiple thalamic channels. In the rodent whisker system, lemniscal and paralemniscal thalamocortical projections, from the ventral posteromedial nucleus (VPM) and posterior medial nucleus (POm) respectively, carry distinct types of sensory information to cortex. Little is known about how these separate streams of activity are parsed and integrated within the neocortical microcircuit. We used quantitative laser scanning photostimulation to probe the organization of functional thalamocortical and ascending intracortical projections in the mouse barrel cortex. To map the thalamocortical projections, we recorded from neocortical excitatory neurons while stimulating VPM or POm. Neurons in layers (L)4, L5, and L6A received dense input from thalamus (L4, L5B, and L6A from VPM; and L5A from POm), whereas L2/3 neurons rarely received thalamic input. We further mapped the lemniscal and paralemniscal circuits from L4 and L5A to L2/3. Lemniscal L4 neurons targeted L3 within a column. Paralemniscal L5A neurons targeted a superficial band (thickness, 60 mum) of neurons immediately below L1, defining a functionally distinct L2 in the mouse barrel cortex. L2 neurons received input from lemniscal L3 cells and paralemniscal L5A cells spread over multiple columns. Our data indicate that lemniscal and paralemniscal information is segregated into interdigitated cortical layers.}, Author = {Bureau, Ingrid and von Saint Paul, Francisca and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {Vibrissae;Microtomy;24 Pubmed search results 2008;research support, non-u.s. gov't;21 Neurophysiology;21 Circuit structure-function;research support, n.i.h., extramural;Brain Mapping;Afferent Pathways;Animals;Mice;Neurons, Afferent;Somatosensory Cortex;Thalamus}, Month = {11}, Nlm_Id = {101183755}, Number = {12}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.}, Pages = {e382}, Pii = {06-PLBI-RA-0726R2}, Pubmed = {17121453}, Title = {Interdigitated paralemniscal and lemniscal pathways in the mouse barrel cortex}, Uuid = {B86CF62E-3250-4F05-978A-20C5604EA168}, Volume = {4}, Year = {2006}, url = {papers/Bureau_PLoSBiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0040382}} @article{Burns:1992, Abstract = {Comparison of the beta-tubulin sequences with the equilibrium colchicine Ka and the Ki for inhibition by podophyllotoxin suggests that residue beta:316 is directly involved in binding the common trimethoxyphenyl-(or A-) ring. By contrast, the analysis indicates that the local hydrophobicity affects the rate of one of the two conformational changes associated with colchicine binding but does not determine the affinity of the colchicine-binding site. 0014-5793 Journal Article Review Review, Tutorial}, Author = {Burns, R. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {FEBS Lett}, Keywords = {Colchicine/chemistry/*metabolism;EE, T abstr;Binding Sites;Molecular Sequence Data;Sequence Alignment;08 Aberrant cell cycle;Tubulin/*metabolism;Amino Acid Sequence;Animals}, Number = {3}, Organization = {Biophysics Section, Blackett Laboratory, Imperial College of Science, Technology and Medicine, London, UK.}, Pages = {205-8}, Pubmed = {1544399}, Title = {Analysis of the colchicine-binding site of beta-tubulin}, Uuid = {08D3BE1F-F49D-4EF0-A6C4-14CE23DA14C0}, Volume = {297}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1544399}} @article{Burns:1993, Abstract = {The restricted host-cell range and low titer of retroviral vectors limit their use for stable gene transfer in eukaryotic cells. To overcome these limitations, we have produced murine leukemia virus-derived vectors in which the retroviral envelope glycoprotein has been completely replaced by the G glycoprotein of vesicular stomatitis virus. Such vectors can be concentrated by ultracentrifugation to titers >10(9) colony-forming units/ml and can infect cells, such as hamster and fish cell lines, that are ordinarily resistant to infection with vectors containing the retroviral envelope protein. The ability to concentrate vesicular stomatitis virus G glycoprotein pseudotyped vectors will facilitate gene therapy model studies and other gene transfer experiments that require direct delivery of vectors in vivo. The availability of these pseudotyped vectors will also facilitate genetic studies in nonmammalian species, including the important zebrafish developmental system, through the efficient introduction and expression of foreign genes. 0027-8424 Journal Article}, Author = {Burns, J. C. and Friedmann, T. and Driever, W. and Burrascano, M. and Yee, J. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Hamsters;Human;Animals;Kidney;Transfection;J;Helper Viruses/genetics/metabolism;Cell Line, Transformed;Adenoviruses, Human/*genetics;Moloney murine leukemia virus/*genetics;15 Retrovirus mechanism;Restriction Mapping;Vesicular stomatitis-Indiana virus/*genetics/metabolism;Cytomegalovirus/genetics;*Membrane Glycoproteins;Genes, gag;Genes, pol;Genetic Vectors;Viral Envelope Proteins/*biosynthesis/genetics;Cell Line;Plasmids;Support, U.S. Gov't, P.H.S.;Promoter Regions (Genetics);Dogs}, Number = {17}, Organization = {Department of Pediatrics, University of California, San Diego School of Medicine, La Jolla 92093.}, Pages = {8033-7}, Pubmed = {8396259}, Title = {Vesicular stomatitis virus G glycoprotein pseudotyped retroviral vectors: concentration to very high titer and efficient gene transfer into mammalian and nonmammalian cells}, Uuid = {E6FD4BE5-DFA9-4A2C-86A6-6F8570800528}, Volume = {90}, Year = {1993}, url = {papers/Burns_ProcNatlAcadSciUSA1993.pdf}} @article{Burns:2006, Abstract = {Thymidine analogs, including bromodeoxyuridine, chlorodeoxyuridine, iododeoxyuridine, and tritiated thymidine, label dividing cells by incorporating into DNA during S phase of cell division and are widely employed to identify cells transplanted into the central nervous system. However, the potential for transfer of thymidine analogs from grafted cells to dividing host cells has not been thoroughly tested. We here demonstrate that graft-derived thymidine analogs can become incorporated into host neural precursors and glia. Large numbers of labeled neurons and glia were found 3-12 weeks after transplantation of thymidine analog-labeled live stem cells, suggesting differentiation of grafted cells. Remarkably, however, similar results were obtained after transplantation of dead cells or labeled fibroblasts. Our findings reveal for the first time that thymidine analog labeling may not be a reliable means of identifying transplanted cells, particularly in highly proliferative environments such as the developing, neurogenic, or injured brain.}, Author = {Burns, Terry C. and Ortiz-Gonz{\'a}lez, Xilma R. and Guti{\'e}rrez-P{\'e}rez, Mar{\'\i}a and Keene, C. Dirk and Sharda, Rohit and Demorest, Zachary L. and Jiang, Yuehua and Nelson-Holte, Molly and Soriano, Mario and Nakagawa, Yasushi and Luquin, Mar{\'\i}a Rosario and Garcia-Verdugo, Jose Manuel and Pr{\'o}sper, Felipe and Low, Walter C. and Verfaillie, Catherine M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {Pregnancy;research support, n.i.h., extramural ;Animals;Biological Transport, Active;Stem Cell Transplantation;Rats;Rats, Inbred SHR;Brain;Thymidine;Female;Rats, Sprague-Dawley;in vitro ;Mice, Transgenic;Cell Proliferation;research support, non-u.s. gov't ;Animals, Newborn;Neuroglia;Neurons;Mice;24 Pubmed search results 2008;Central Nervous System;Bromodeoxyuridine}, Month = {4}, Nlm_Id = {9304532}, Number = {4}, Organization = {Stem Cell Institute, University of Minnesota, 420 Delaware Street, Minneapolis, Minnesota 55455, USA.}, Pages = {1121-7}, Pii = {2005-0463}, Pubmed = {16373692}, Title = {Thymidine analogs are transferred from prelabeled donor to host cells in the central nervous system after transplantation: a word of caution}, Uuid = {43CB330D-9013-402B-A3F4-B9A655F036A3}, Volume = {24}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1634/stemcells.2005-0463}} @article{Burrone:2006, Abstract = {Genetically encoded fluorescent probes have become indispensable tools in the biological sciences. Studies of synaptic vesicle recycling have been facilitated by a group of GFP-derived probes called pHluorins. These probes exploit changes in pH that accompany exocytosis and recapture of synaptic vesicles. Here we describe how these synaptic tracers can be used in rodent hippocampal neurons to monitor the synaptic vesicle cycle in real time and to obtain mechanistic insights about it. Synapses can be observed in living samples using a wide-field fluorescence microscope and a cooled charge-coupled device camera. A simple specimen chamber allows electrical stimulation of synapses to evoke exocytosis in a precisely controlled manner. We present protocols to measure various parameters of the synaptic vesicle cycle. This technique can be easily adapted to study different classes of synapses from wild-type and mutant mice. Once cultured neurons expressing synaptopHluorin are available, the whole procedure should take about 2 h.}, Author = {Burrone, Juan and Li, Zhiying and Murthy, Venkatesh N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1750-2799}, Journal = {Nat Protoc}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Nlm_Id = {101284307}, Number = {6}, Organization = {MRC Center for Developmental Neurobiology, King's College London, London SE1 1UL, UK.}, Pages = {2970-8}, Pii = {nprot.2006.449}, Pubmed = {17406557}, Title = {Studying vesicle cycling in presynaptic terminals using the genetically encoded probe synaptopHluorin}, Uuid = {9DAA57D0-6FA5-4743-8B02-E4ED6503D192}, Volume = {1}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nprot.2006.449}} @article{Bush:1999, Abstract = {Reactive astrocytes adjacent to a forebrain stab injury were selectively ablated in adult mice expressing HSV-TK from the Gfap promoter by treatment with ganciclovir. Injured tissue that was depleted of GFAP-positive astrocytes exhibited (1) a prolonged 25-fold increase in infiltration of CD45-positive leukocytes, including ultrastructurally identified monocytes, macrophages, neutrophils, and lymphocytes, (2) failure of blood-brain barrier (BBB) repair, (3) substantial neuronal degeneration that could be attenuated by chronic glutamate receptor blockade, and (4) a pronounced increase in local neurite outgrowth. These findings show that genetic targeting can be used to ablate scar-forming astrocytes and demonstrate roles for astrocytes in regulating leukocyte trafficking, repairing the BBB, protecting neurons, and restricting nerve fiber growth after injury in the adult central nervous system. 0896-6273 Journal Article}, Author = {Bush, T. G. and Puvanachandra, N. and Horner, C. H. and Polito, A. and Ostenfeld, T. and Svendsen, C. N. and Mucke, L. and Johnson, M. H. and Sofroniew, M. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuron}, Keywords = {G;Nerve Degeneration/*pathology;Ganciclovir/pharmacology;Animals;Leukocytes/metabolism/*pathology;Gene Expression Regulation;Wounds, Stab/*pathology;Brain Injuries/*pathology;Hippocampus/pathology;Female;Cell Count;Mice, Transgenic;Astrocytes/metabolism/*pathology;11 Glia;Simplexvirus/enzymology/genetics;Blood-Brain Barrier;*Cell Movement;Neurons/metabolism/pathology;Support, Non-U.S. Gov't;Histocytochemistry;Thymidine Kinase/biosynthesis/genetics;Mice;Glial Fibrillary Acidic Protein/biosynthesis/genetics;Neurites/metabolism/*pathology}, Number = {2}, Organization = {Medical Research Council Cambridge Centre for Brain Repair, and Department of Anatomy, University of Cambridge, United Kingdom.}, Pages = {297-308}, Pubmed = {10399936}, Title = {Leukocyte infiltration, neuronal degeneration, and neurite outgrowth after ablation of scar-forming, reactive astrocytes in adult transgenic mice}, Uuid = {AB05AF8E-19E9-42A5-A73D-F0845BDBB6FD}, Volume = {23}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10399936}} @article{Bushey:2007, Abstract = {In mammals, sleep is thought to be important for health, cognition, and memory. Fruit flies share most features of mammalian sleep, and a recent study found that Drosophila lines carrying loss-of-function mutations in Shaker (Sh) are short sleeping, suggesting that the Sh current plays a major role in regulating daily sleep amount. The Sh current is potentiated by a beta modulatory subunit coded by Hyperkinetic (Hk). Here, we demonstrate that severe loss-of-function mutations of Hk reduce sleep and do so primarily by affecting the Sh current. Moreover, we prove, using a transgenic approach, that a wild-type copy of Hk is sufficient to restore normal sleep. Furthermore, we show that short-sleeping Hk mutant lines have a memory deficit, whereas flies carrying a weaker hypomorphic Hk allele have normal sleep and normal memory. By comparing six short-sleeping Sh lines with two normal sleeping ones, we also found that only alleles that reduce sleep also impair memory. These data identify a gene, Hk, which is necessary to maintain normal sleep, and provide genetic evidence that short sleep and poor memory are linked.}, Author = {Bushey, Daniel and Huber, Reto and Tononi, Giulio and Cirelli, Chiara}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008;Mutation;research support, non-u.s. gov't;21 Neurophysiology;Animals, Genetically Modified;Drosophila Proteins;Shaker Superfamily of Potassium Channels;research support, u.s. gov't, non-p.h.s.;Drosophila;research support, n.i.h., extramural;Animals;Memory Disorders;Potassium Channels;Sleep;Hyperkinesis}, Month = {5}, Nlm_Id = {8102140}, Number = {20}, Organization = {Department of Psychiatry, University of Wisconsin-Madison, Madison, Wisconsin 53719, USA.}, Pages = {5384-93}, Pii = {27/20/5384}, Pubmed = {17507560}, Title = {Drosophila Hyperkinetic mutants have reduced sleep and impaired memory}, Uuid = {959C6B25-B7D8-4899-B222-4314087047EB}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0108-07.2007}} @article{Bushong:2002, Abstract = {Protoplasmic astrocytes are increasingly thought to interact extensively with neuronal elements in the brain and to influence their activity. Recent reports have also begun to suggest that physiologically, and perhaps functionally, diverse forms of these cells may be present in the CNS. Our current understanding of astrocyte form and distribution is based predominantly on studies that used the astrocytic marker glial fibrillary acidic protein (GFAP) and on studies using metal-impregnation techniques. The prevalent opinion, based on studies using these methods, is that astrocytic processes overlap extensively and primarily share the underlying neuropil. However, both of these techniques have serious shortcomings for visualizing the interactions among these structurally complex cells. In the present study, intracellular injection combined with immunohistochemistry for GFAP show that GFAP delineates only approximately 15\%of the total volume of the astrocyte. As a result, GFAP-based images have led to incorrect conclusions regarding the interaction of processes of neighboring astrocytes. To investigate these interactions in detail, groups of adjacent protoplasmic astrocytes in the CA1 stratum radiatum were injected with fluorescent intracellular tracers of distinctive emissive wavelengths and analyzed using three-dimensional (3D) confocal analysis and electron microscopy. Our findings show that protoplasmic astrocytes establish primarily exclusive territories. The knowledge of how the complex morphology of protoplasmic astrocytes affects their 3D relationships with other astrocytes, oligodendroglia, neurons, and vasculature of the brain should have important implications for our understanding of nervous system function.}, Author = {Bushong, E. A. and Martone, M. E. and Jones, Y. Z. and Ellisman, M. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Cytoplasm/ultrastructure;G;Rats;Microscopy, Confocal;Iontophoresis;Animal;Rats, Sprague-Dawley;Glial Fibrillary Acidic Protein/analysis/metabolism;11 Glia;Male;Oxidation-Reduction;Photochemistry;Cell Size;Isoquinolines;Astrocytes/*cytology/metabolism/ultrastructure;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Microscopy, Electron;Hippocampus/*anatomy &histology/metabolism/ultrastructure}, Number = {1}, Organization = {National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, California 92093-0608, USA.}, Pages = {183-92.}, Title = {Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains}, Uuid = {C7BA755F-4027-437E-B857-9E5A925E61D1}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11756501%20http://www.jneurosci.org/cgi/content/full/22/1/183%20http://www.jneurosci.org/cgi/content/abstract/22/1/183}} @article{Butler:1994, Abstract = {The large body of evidence that supports the hypothesis that the dorsal cortex and dorsal ventricular ridge of non-mammalian (non-synapsid) amniotes form the dorsal pallium and are homologous as a set of specified populations of cells to respective sets of cells in mammalian isocortex is reviewed. Several recently taken positions that oppose this hypothesis are examined and found to lack a solid foundation. A cladistic analysis of multiple features of the dorsal pallium in amniotes was carried out in order to obtain a morphotype for the common ancestral stock of all living amniotes, i.e., a captorhinomorph amniote. A previous cladistic analysis of the dorsal thalamus (Butler, A.B., The evolution of the dorsal thalamus of jawed vertebrates, including mammals: cladistic analysis and a new hypothesis, Brain Res. Rev., 19 (1994) 29-65; this issue, previous article) found that two fundamental divisions of the dorsal thalamus can be recognized--termed the lemnothalamus in reference to predominant lemniscal sensory input and the collothalamus in reference to predominant input from the midbrain roof. These two divisions are both elaborated in amniotes in that their volume is increased and their nuclei are laterally migrated in comparison with anamniotes. The present cladistic analysis found that two corresponding, fundamental divisions of the dorsal pallium were present in captorhinomorph amniotes and were expanded relative to their condition in anamniotes. Both the lemnothalamic medial pallial division and the collothalamic lateral pallial division were subsequently further markedly expanded in the synapsid line leading to mammals, along with correlated expansions of the lemnothalamus and collothalamus. Only the collothalamic lateral pallial division--along with the collothalamus--was subsequently further markedly expanded in the non-synapsid amniote line that gave rise to diapsid reptiles, birds and turtles. In the synapsid line leading to mammals, an increase in the degree of radial organization of both divisions of the dorsal pallium also occurred, resulting in an 'outside-in'migration pattern during development. The lemnothalamic medial division of the dorsal pallium has two parts. The medial part forms the subicular, cingulate, prefrontal, sensorimotor, and related cortices in mammals and the medial part of the dorsal cortex in non-synapsid amniotes. The lateral part forms striate cortex in mammals and the lateral part of dorsal cortex (or pallial thickening or visual Wulst) in non-synapsid amniotes. Specific fields within the collothalamic lateral division of the dorsal pallium form the extrastriate, auditory, secondary somatosensory, and related cortices in mammals and the visual, auditory, somatosensory, and related areas of the dorsal ventricular ridge in non-synapsid amniotes. 0165-0173 Journal Article Review Review, Academic}, Author = {Butler, A. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Brain Res Brain Res Rev}, Keywords = {Cerebral Cortex/*anatomy &histology;*Phylogeny;Telencephalon/*anatomy &histology;*Evolution;N;Vertebrates/*anatomy &histology;Animals;19 Neocortical evolution}, Number = {1}, Organization = {Ivory Tower Neurobiology Institute, Arlington, VA 22207.}, Pages = {66-101}, Pubmed = {8167660}, Title = {The evolution of the dorsal pallium in the telencephalon of amniotes: cladistic analysis and a new hypothesis}, Uuid = {6854D7BE-6A31-4575-9A1F-DD6B82B043DF}, Volume = {19}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8167660}} @article{Butler:1994a, Abstract = {The evolution of the dorsal thalamus in various vertebrate lineages of jawed vertebrates has been an enigma, partly due to two prevalent misconceptions: the belief that the multitude of nuclei in the dorsal thalamus of mammals could be meaningfully compared neither with the relatively few nuclei in the dorsal thalamus of anamniotes nor with the intermediate number of dorsal thalamic nuclei of other amniotes and a definition of the dorsal thalamus that too narrowly focused on the features of the dorsal thalamus of mammals. The cladistic analysis carried out here allows us to recognize which features are plesiomorphic and which apomorphic for the dorsal thalamus of jawed vertebrates and to then reconstruct the major changes that have occurred in the dorsal thalamus over evolution. Embryological data examined in the context of Von Baerian theory (embryos of later-descendant species resemble the embryos of earlier-descendant species to the point of their divergence) supports a new 'Dual Elaboration Hypothesis'of dorsal thalamic evolution generated from this cladistic analysis. From the morphotype for an early stage in the embryological development of the dorsal thalamus of jawed vertebrates, the divergent, sequential stages of the development of the dorsal thalamus are derived for each major radiation and compared. The new hypothesis holds that the dorsal thalamus comprises two basic divisions--the collothalamus and the lemnothalamus--that receive their predominant input from the midbrain roof and (plesiomorphically) from lemniscal pathways, including the optic tract, respectively. Where present, the collothalamic, midbrain-sensory relay nuclei are homologous to each other in all vertebrate radiations as discrete nuclei. Within the lemnothalamus, the dorsal lateral geniculate nucleus of mammals and the dorsal lateral optic nucleus of non-synapsid amniotes (diapsid reptiles, birds and turtles) are homologous as discrete nuclei; most or all of the ventral nuclear group of mammals is homologous as a field to the lemniscal somatosensory relay and motor feedback nuclei of non-synapsid amniotes; the anterior, intralaminar and medial nuclear groups of mammals are collectively homologous as a field to both the dorsomedial and dorsolateral (including perirotundal) nuclei of non-synapsid amniotes; the anterior, intralaminar, medial and ventral nuclear groups and the dorsal lateral geniculate nucleus of mammals are collectively homologous as a field to the nucleus anterior of anamniotes, as are their homologues in non-synapsid amniotes. In the captorhinomorph ancestors of extant land vertebrates, both divisions of the dorsal thalamus were elaborated to some extent due to an increase in proliferation and lateral migration of neurons during development.(ABSTRACT TRUNCATED AT 400 WORDS) 0165-0173 Journal Article Review Review, Academic}, Author = {Butler, A. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Brain Res Brain Res Rev}, Keywords = {*Phylogeny;Vertebrates/*anatomy &histology/embryology;Mammals/*anatomy &histology/embryology;Thalamic Nuclei/*anatomy &histology/embryology;N;*Evolution;Animals;Jaw;19 Neocortical evolution}, Number = {1}, Organization = {Ivory Tower Neurobiology Institute, Arlington, VA 22207.}, Pages = {29-65}, Pubmed = {8167659}, Title = {The evolution of the dorsal thalamus of jawed vertebrates, including mammals: cladistic analysis and a new hypothesis}, Uuid = {83FB4D15-BB3F-443E-B9DD-AAB8714D571E}, Volume = {19}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8167659}} @article{Butler:1999, Abstract = {0166-2236 Congresses}, Author = {Butler, A. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Trends Neurosci}, Keywords = {Mammals/*physiology;Evolution, Molecular;Neocortex/*physiology;N;*Evolution;Animals;19 Neocortical evolution}, Number = {8}, Organization = {Krasnow Institute for Advanced Study and the Dept of Psychology, George Mason University, Fairfax, VA 22030, USA.}, Pages = {332-4}, Pubmed = {10465725}, Title = {Whence and whither cortex?}, Uuid = {D95E9A0D-28E2-4166-8D07-AB7E2F17D22A}, Volume = {22}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10465725}} @article{Butovsky:2007, Abstract = {Microglia are resident cells in the central nervous system (CNS), of hematopoietic origin with a high plasticity. In this study, we examined whether adaptive immune system, involving in CNS maintenance and repair, can induce microglia to express markers of neural cells. We show that long exposure (above 10 days) of microglia to low doses (10 ng/ml) of the 'proinflammatory' T-cell derived cytokine, IFN-gamma, induced them to express neuronal markers including gamma-aminobutyric acid (GABA) and glutamic acid decarboxylase (GAD-67). In contrast, exposure of microglia to low doses (10 ng/ml) of the 'anti-inflammatory' T-cell derived cytokine, IL-4, induced the expression of oligodendrocyte markers and dendritic cell (DC) marker, CD11c. The microglial origin of the neural-like cells was confirmed using microglia from transgenic mice expressing GFP under promoter of the chemokine fractalkine receptor CX(3)CR1, and diphtheria toxin receptor, under CD11c promoter. This study emphasizes that microglial plasticity includes their ability to give rise to neural-like cells and shows that cytokines produced by the adaptive immune system are involved in these processes.}, Author = {Butovsky, Oleg and Bukshpan, Shay and Kunis, Gilad and Jung, Steffen and Schwartz, Michal}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {gamma-Aminobutyric Acid;Animals;Interleukin-4;Brain;Interferon Type II;Microglia;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;research support, non-u.s. gov't;08 Aberrant cell cycle;Time Factors;14 Immune;Green Fluorescent Proteins;Animals, Newborn;Glutamate Decarboxylase;Receptors, Chemokine;Mice;24 Pubmed search results 2008;Isoenzymes;Nerve Tissue Proteins;Antigens, CD11c}, Month = {7}, Nlm_Id = {9100095}, Number = {3}, Organization = {Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.}, Pages = {490-500}, Pii = {S1044-7431(07)00105-4}, Pubmed = {17560122}, Title = {Microglia can be induced by IFN-gamma or IL-4 to express neural or dendritic-like markers}, Uuid = {5CD8DEDC-DE31-4955-83F6-2BFA5BA36E85}, Volume = {35}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2007.04.009}} @article{Butt:1996, Abstract = {The glia response to Wallerian degeneration was studied in optic nerves 21 days after unilateral enucleation (PED21) of immature rats, 21 days old (P21), using immunohistochemical labelling. Nerves from normal P21 and P42 nerves were also studied for comparison. At PED21, there was a virtual loss of axons apart from a few solitary fibres of unknown origin. The nerve comprised a homogeneous glial scar tissue formed by dense astrocyte processes, oriented parallel to the long axis of the nerve along the tracks of degenerated axons. Astrocytes were almost perfectly co-labelled by antibodies to glial fibrillary acid protein and vimentin in both normal and transected nerves. However, there was a small population of VIM+GFAP- cells in normal P21 and P42 nerves, and we discuss the possibility that they correspond to O-2A progenitor cells described in vitro. Significantly, double immunofluorescence labelling in transected nerves revealed a distinct population of hypertrophic astrocytes which were GFAP+VIM-. These cells represented a novel morphological and antigenic subtype of reactive astrocyte. It was also noted that the number of oligodendrocytes in transected nerves did not appear to be less than in normal nerves, on the basis of double immunofluorescence staining for carbonic anhydrase II, myelin oligodendrocyte glycoprotein, myelin basic protein, glial fibrillary acid protein and ED-1 (for macrophages), although it was not excluded that a small proportion may have been microglia. A further prominent feature of transected nerves was that they contained a substantial amount of myelin debris, notwithstanding that OX-42 and ED1 immunostaining showed that there were abundant microglia and macrophages, sufficient for the rapid and almost complete removal of axonal debris. In conclusion, glial cells in the immature P21 rat optic nerve reacted to Wallerian degeneration in a way equivalent to the adult CNS, i.e. astrocytes underwent pronounced reactive changes and formed a dense glial scar, oligodendrocytes persisted and were not dependent on axons for their continued survival, and there was ineffective phagocytosis of myelin possibly due to incomplete activation of microglia/macrophages.}, Author = {Butt, A. M. and Kirvell, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Fluorescent Dyes;Animals;Astrocytes;In Vitro;Rats;Myelin Basic Proteins;Myelin-Associated Glycoprotein;Microglia;Oligodendroglia;Optic Nerve;Vimentin;Axons;Rats, Wistar;Not relevant;11 Glia;Animals, Newborn;Eye Enucleation;Support, Non-U.S. Gov't;Wallerian Degeneration;Neuroglia;Age Factors;Immunohistochemistry;Glial Fibrillary Acidic Protein}, Medline = {96432734}, Month = {6}, Nlm_Id = {0364620}, Number = {6}, Organization = {Division of Physiology, UMDS, St. Thomas' Hospital, London, UK.}, Pages = {381-92}, Pubmed = {8835786}, Title = {Glial cells in transected optic nerves of immature rats. II. An immunohistochemical study}, Uuid = {682A5121-D491-42E1-A5D5-623F1EA087AC}, Volume = {25}, Year = {1996}} @article{Butt:2002, Abstract = {In the adult CNS, antibodies to the NG2 chondroitin sulphate proteoglycan (CSPG) label a large population of glia that have the antigenic phenotype of oligodendrocyte progenitor cells (OPC). However, NG2 expressing glia have the morphological phenotype of astrocytes, not OPC. We propose adult NG2 expressing glia are a distinct mature glial type, which we have called syantocytes or synantoglia after the Greek 'to contact', because they specifically contact neurons and axons at synapses and nodes of Ranvier, respectively. Synantocytes are highly complex cells that elaborate multiple branching processes and are an equally significant population in both white and grey matter. We provide evidence that phenotypically distinct synantocytes develop postnatally and that neither postnatal nor adult synantocytes depend on axons for their survival, indicating they respond with markedly different behaviours to the environmental cues and axonal signals that control the differentiation of OPC into oligodendrocytes. The primary response of synantocytes to changes in the CNS environment is a rapid and localised reactive gliosis. Reactive synantocytes interact intimately with astrocytes and macrophages at lesion sites, consistent with them playing a key role in the orchestration of scar formation that protects the underlying neural tissue. It is our hypothesis that synantocytes are specialised to monitor and respond to changes in the integrity of the CNS, by way of their cellular contacts, repertoire of plasmalemmal receptors and the NG2 molecule itself. To paraphrase Del Rio Hortega, we propose that synantocytes are the fifth element in the CNS, in addition to neurons, astrocytes, oligodendrocytes and microglia. 0300-4864 Journal Article}, Author = {Butt, A. M. and Kiff, J. and Hubbard, P. and Berry, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurocytol}, Keywords = {11 Glia;G pdf}, Number = {6-7}, Organization = {Centre for Neuroscience Research, GKT School of Biomedical Sciences, King's College, London SE1 1UL, United Kingdom. arthur.butt\@kcl.ac.uk}, Pages = {551-65}, Pubmed = {14501223}, Title = {Synantocytes: new functions for novel NG2 expressing glia}, Uuid = {C7E35671-6B78-44CF-A13F-205760E9C08B}, Volume = {31}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14501223}} @article{Butt:2005, Abstract = {Interneurons of the cerebral cortex represent a heterogeneous population of cells with important roles in network function. At present, little is known about how these neurons are specified in the developing telencephalon. To explore whether this diversity is established in the early progenitor populations, we conducted in utero fate-mapping of the mouse medial and caudal ganglionic eminences (MGE and CGE, respectively), from which most cortical interneurons arise. Mature interneuron subtypes were assessed by electrophysiological and immunological analysis, as well as by morphological reconstruction. At E13.5, the MGE gives rise to fast-spiking (FS) interneurons, whereas the CGE generates predominantly regular-spiking interneurons (RSNP). Later at E15.5, the CGE produces RSNP classes distinct from those generated from the E13.5 CGE. Thus, we provide evidence that the spatial and temporal origin of interneuron precursors in the developing telencephalic eminences predicts the intrinsic physiological properties of mature interneurons.}, Author = {Butt, Simon J. B. and Fuccillo, Marc and Nery, Susana and Noctor, Steven and Kriegstein, Arnold and Corbin, Joshua G. and Fishell, Gord}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cell Aging;Cell Differentiation;Animals;Stem Cell Transplantation;Cell Movement;Telencephalon;Embryonic Development;Reaction Time;Embryo;Animals, Newborn;Action Potentials;Cerebral Cortex;21 Neurophysiology;Mice;Interneurons;Immunohistochemistry;24 Pubmed search results 2008;Stem Cells;12 Interneuron development}, Month = {11}, Nlm_Id = {8809320}, Number = {4}, Organization = {Developmental Genetics Program and the Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, New York 10016, USA.}, Pages = {591-604}, Pii = {S0896-6273(05)00934-7}, Pubmed = {16301176}, Title = {The temporal and spatial origins of cortical interneurons predict their physiological subtype}, Uuid = {6EBB1436-6EF1-4BDC-8407-1D7C80E03A7B}, Volume = {48}, Year = {2005}, url = {papers/Butt_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.09.034}} @article{Buttery:2006, Abstract = {The morphological and functional differentiation of neuronal dendrites is controlled through transcriptional programs and cell-cell signaling. Synaptic activity is thought to play an important role in the maturation of dendritic arbors, but the signaling pathways that couple neuronal activity and morphological changes in dendrites are not well understood. We explored the function of alpha1-chimaerin, a neuronal diacylglycerol-binding protein with a Rho GTPase-activating protein domain that inactivates Rac1. We find that stimulation of phospholipase Cbeta-coupled cell surface receptors recruits alpha1-chimaerin to the plasma membrane of cultured hippocampal neurons. We further show that alpha1-chimaerin protein levels are controlled by synaptic activity and that increased alpha1-chimaerin expression results in the pruning of dendritic spines and branches. This pruning activity requires both the diacylglycerol-binding and Rac GTPase-activating protein activity of alpha1-chimaerin. Suppression of alpha1-chimaerin expression resulted in increased process growth from the dendritic shaft and from spine heads. Our data suggest that alpha1-chimaerin is an activity-regulated Rho GTPase regulator that is activated by phospholipase Cbeta-coupled cell surface receptors and contributes to pruning of dendritic arbors.}, Author = {Buttery, Philip and Beg, Asim A. and Chih, Ben and Broder, Arkady and Mason, Carol A. and Scheiffele, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {10 Development;research support, n.i.h., extramural ;Signal Transduction;Animals;Gene Expression Regulation;Humans;Tissue Culture Techniques;10 Structural plasticity;Diglycerides;Protein Transport;Cell Membrane;Hippocampus;Phospholipase C;Dendrites;research support, non-u.s. gov't ;Cell Line;Cell Shape;Mice;24 Pubmed search results 2008;Isoenzymes;Chimerin 1}, Month = {2}, Nlm_Id = {7505876}, Number = {6}, Organization = {Department of Pathology and Cell Biology, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, P&S 14-509, 630 West 168th Street, New York, NY 10032, USA.}, Pages = {1924-9}, Pii = {0510655103}, Pubmed = {16446429}, Title = {The diacylglycerol-binding protein alpha1-chimaerin regulates dendritic morphology}, Uuid = {AB641F84-3317-45C5-A46E-8364491CC8C8}, Volume = {103}, Year = {2006}, url = {papers/Buttery_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0510655103}} @article{Buttner:2002, Abstract = {Sialylation is essential for development and regeneration in mammals. Using N-propanoylmannosamine, a novel precursor of sialic acid, we were able to incorporate unnatural sialic acids with a prolonged N-acyl side chain (e.g., N-propanoylneuraminic acid) into cell surface glycoconjugates. Here we report that this biochemical engineering of sialic acid leads to a stimulation of neuronal cells. Both PC12 cells and cerebellar neurons showed a significant increase in neurite outgrowth after treatment with this novel sialic acid precursor. Furthermore, also the reestablishment of the perforant pathway was stimulated in brain slices. In addition, we surprisingly identified several cytosolic proteins with regulatory functions, which are differentially expressed after treatment with N-propanoylmannosamine. Because sialic acid is the only monosaccharide that is activated in the nucleus, we hypothesize that transcription could be modulated by the unnatural CMP-N-propanoylneuraminic acid and that sialic acid activation might be a general tool to regulate cellular functions, such as neurite outgrowth. 1529-2401 Journal Article}, Author = {Buttner, B. and Kannicht, C. and Schmidt, C. and Loster, K. and Reutter, W. and Lee, H. Y. and Nohring, S. and Horstkorte, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:43 -0400}, Journal = {J Neurosci}, Keywords = {Axons/drug effects/*physiology;Mice, Inbred BALB C;Cell Differentiation/drug effects;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Neuraminic Acids/metabolism/pharmacology;Animals;Cells, Cultured;Rats;T pdf;Cerebellum/cytology;Female;23 Technique;Sialic Acids/*chemistry/*metabolism;Hexosamines/metabolism/pharmacology;PC12 Cells;Male;Perforant Pathway/cytology/drug effects;Support, Non-U.S. Gov't;Electrophoresis, Gel, Two-Dimensional;Neurons/cytology/drug effects/*metabolism;Membrane Glycoproteins/metabolism;Mice;Neurites/drug effects/physiology;Cell Membrane/chemistry/*metabolism;Nerve Regeneration/drug effects/physiology;Proteome/analysis}, Number = {20}, Organization = {Institut fur Molekularbiologie und Biochemie, Fachbereich Humanmedizin, Freie Universitat Berlin, D-14195 Berlin-Dahlem, Germany.}, Pages = {8869-75}, Title = {Biochemical engineering of cell surface sialic acids stimulates axonal growth}, Uuid = {DD96ACA2-2490-4576-AD4E-0467ADCCDFFC}, Volume = {22}, Year = {2002}, url = {papers/Buttner_JNeurosci2002.pdf}} @article{Butz:2006, Abstract = {We describe a strongly biologically motivated artificial neural network approach to model neurogenesis and synaptic turnover as it naturally occurs for example in the hippocampal dentate gyrus (DG) of the developing and adult mammalian and human brain. The results suggest that cell proliferation (CP) has not only a functional meaning for computational tasks and learning but is also relevant for maintaining homeostatic stability of the neural activity. Moderate rates of CP buffer disturbances in input activity more effectively than networks without or very high CP. Up to a critical mark an increase of CP enhances synaptogenesis which might be beneficial for learning. However, higher rates of CP are rather ineffective as they destabilize the network: high CP rates and a disturbing input activity effect a reduced cell survival. By these results the simulation model sheds light on the recurrent interdependence of structure and function in biological neural networks especially in hippocampal circuits and the interacting morphogenetic effects of neurogenesis and synaptogenesis.}, Author = {Butz, Markus and Lehmann, Konrad and Dammasch, Ingolf E. and Teuchert-Noodt, Gertraud}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:18 -0400}, Issn = {0893-6080}, Journal = {Neural Netw}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8805018}, Number = {10}, Organization = {Department for Neuroanatomy, University of Bielefeld, Germany.}, Pages = {1490-505}, Pii = {S0893-6080(06)00186-9}, Pubmed = {17014989}, Title = {A theoretical network model to analyse neurogenesis and synaptogenesis in the dentate gyrus}, Uuid = {82370F89-32EE-43B6-94E5-487492C72B04}, Volume = {19}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neunet.2006.07.007}} @article{Buzsaki:1996, Abstract = {In gross anatomical terms, the hippocampal archicortex can be conceived as an "appendage'of the large neocortex. In contrast to neocortical areas, the main output targets of the hippocampus are the same as its main inputs (i.e., the entorhinal cortex). Highly processed information about the external world (the content) reaches the hippocampus via the entorhinal cortex, whereas information about the "internal world'(the context) is conveyed by the subcortical inputs. Removal of the context makes the content illegible, as demonstrated by the observation that the behavioral impairment following surgical removal of hippocampopetal subcortical inputs is as devastating as removing the hippocampus itself. From its strategic anatomical position and input-output connections, it may be suggested that the main function of the hippocampal formation is to modify its inputs by feeding back a processed "reafferent copy'to the neocortex. I hypothesize that neocortico-hippocampal transfer of information and the modification process in neocortical circuitries by the hippocampal output take place in a temporally discontinuous manner and might be delayed by minutes, hours, or days. Acquisition of information may happen very fast during the activated state of the hippocampus associated with theta/gamma oscillations. Intrahippocampal consolidation and the hippocampal-neocortical transfer of the stored representations, on the other hand, is protracted and carried by discrete quanta of cooperative neuronal bursts during slow wave sleep. 1047-3211 Journal Article Review Review, Academic}, Author = {Buzsaki, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cereb Cortex}, Keywords = {18 Classic Neuroanatomy Physiology;Cerebral Cortex/*anatomy &histology;Hippocampus/*anatomy &histology;M;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;Neural Pathways/*anatomy &histology}, Number = {2}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, State University of New Jersey, Newark 07102, USA.}, Pages = {81-92}, Pubmed = {8670641}, Title = {The hippocampo-neocortical dialogue}, Uuid = {B1D3B6AE-833E-469D-9C2E-B0AF4B5FC117}, Volume = {6}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8670641}} @article{Buzsaki:2001, Abstract = {In this issue of Neuron, two laboratories (Deans et al. and Hormuzdi et al.) find that cortical gamma oscillation in vitro is impaired in the Cx36 knockout mouse. What are the implications? 0896-6273 Comment Journal Article}, Author = {Buzsaki, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuron}, Keywords = {18 Classic Neuroanatomy Physiology;Neurons/*physiology;Mice, Knockout;Brain/*physiology;Connexins/deficiency/genetics/*physiology;Pyramidal Cells/physiology;Cerebral Cortex/*physiology;Synapses/physiology;Spinal Cord/physiology;M;Animals;Mice;Nerve Net/*physiology}, Number = {3}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, NJ 07102, USA.}, Pages = {342-4}, Pubmed = {11516391}, Title = {Electrical wiring of the oscillating brain}, Uuid = {ED8AC2CA-AC62-446B-ABDF-620940B24508}, Volume = {31}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11516391}} @article{Buzsaki:2004, Abstract = {How does the brain orchestrate perceptions, thoughts and actions from the spiking activity of its neurons? Early single-neuron recording research treated spike pattern variability as noise that needed to be averaged out to reveal the brain's representation of invariant input. Another view is that variability of spikes is centrally coordinated and that this brain-generated ensemble pattern in cortical structures is itself a potential source of cognition. Large-scale recordings from neuronal ensembles now offer the opportunity to test these competing theoretical frameworks. Currently, wire and micro-machined silicon electrode arrays can record from large numbers of neurons and monitor local neural circuits at work. Achieving the full potential of massively parallel neuronal recordings, however, will require further development of the neuron-electrode interface, automated and efficient spike-sorting algorithms for effective isolation and identification of single neurons, and new mathematical insights for the analysis of network properties.}, Author = {Buzs{\'a}ki, Gy{\"o}rgy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Nerve Net;Neurons;21 Neurophysiology;Neurophysiology;Action Potentials;Electrophysiology;research support, u.s. gov't, p.h.s.;Animals;Brain;Humans;review;Microelectrodes;extracellular;Electrophysiology;in vivo}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, New Jersey 07102, USA. buzsaki\@axon.rutgers.edu}, Pages = {446-51}, Pii = {nn1233}, Pubmed = {15114356}, Title = {Large-scale recording of neuronal ensembles}, Uuid = {D7D4CB8C-1DAA-4F69-BAD8-78896C6B7506}, Volume = {7}, Year = {2004}, url = {papers/Buzsáki_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1233}} @article{Buzsaki:2004a, Abstract = {Clocks tick, bridges and skyscrapers vibrate, neuronal networks oscillate. Are neuronal oscillations an inevitable by-product, similar to bridge vibrations, or an essential part of the brain's design? Mammalian cortical neurons form behavior-dependent oscillating networks of various sizes, which span five orders of magnitude in frequency. These oscillations are phylogenetically preserved, suggesting that they are functionally relevant. Recent findings indicate that network oscillations bias input selection, temporally link neurons into assemblies, and facilitate synaptic plasticity, mechanisms that cooperatively support temporal representation and long-term consolidation of information.}, Author = {Buzs{\'a}ki, Gy{\"o}rgy and Draguhn, Andreas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Animals;Synapses;Humans;Neuronal Plasticity;Synaptic Transmission;Brain;review;Biological Clocks;Nerve Net;Learning;research support, u.s. gov't, p.h.s.;Cerebral Cortex;Neurons;21 Neurophysiology;Membrane Potentials;21 Cortical oscillations;24 Pubmed search results 2008;Electroencephalography}, Month = {6}, Nlm_Id = {0404511}, Number = {5679}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, State University of New Jersey, Newark, NJ 07102, USA. buzsaki\@axon.rutgers.edu}, Pages = {1926-9}, Pii = {304/5679/1926}, Pubmed = {15218136}, Title = {Neuronal oscillations in cortical networks}, Uuid = {6DAF4739-E74A-4363-B423-AE894567956F}, Volume = {304}, Year = {2004}, url = {papers/Buzsáki_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1099745}} @article{Bystron:2006, Abstract = {We describe a distinctive, widespread population of neurons situated beneath the pial surface of the human embryonic forebrain even before complete closure of the neural tube. These 'predecessor' cells include the first neurons seen in the primordium of the cerebral cortex, before the onset of local neurogenesis. Morphological analysis, combined with the study of centrosome location, regional transcription factors and patterns of mitosis and neurogenesis, indicates that predecessor cells invade the cortical primordium by tangential migration from the subpallium. These neurons, described here for the first time, precede all other known cell types of the developing cortex.}, Author = {Bystron, Irina and Rakic, Pasko and Moln{\'a}r, Zolt{\'a}n and Blakemore, Colin}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008;Cell Differentiation;Research Support, Non-U.S. Gov't;Fetus;Immunohistochemistry;Nerve Tissue Proteins;Comparative Study;Stem Cells;Research Support, U.S. Gov't, P.H.S.;Gene Expression;Body Patterning;Humans;Cell Movement;Cerebral Cortex;Neurons;Transcription Factors}, Month = {7}, Nlm_Id = {9809671}, Number = {7}, Organization = {Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford, Oxfordshire OX13PT, UK. irina.bystron\@physiol.ox.ac.uk}, Pages = {880-6}, Pii = {nn1726}, Pubmed = {16783367}, Title = {The first neurons of the human cerebral cortex}, Uuid = {1D3B526D-9F97-4B4B-96AC-0A2236DC827D}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1726}} @article{Cabantous:2005, Abstract = {Existing protein tagging and detection methods are powerful but have drawbacks. Split protein tags can perturb protein solubility or may not work in living cells. Green fluorescent protein (GFP) fusions can misfold or exhibit altered processing. Fluorogenic biarsenical FLaSH or ReASH substrates overcome many of these limitations but require a polycysteine tag motif, a reducing environment and cell transfection or permeabilization. An ideal protein tag would be genetically encoded, would work both in vivo and in vitro, would provide a sensitive analytical signal and would not require external chemical reagents or substrates. One way to accomplish this might be with a split GFP, but the GFP fragments reported thus far are large and fold poorly, require chemical ligation or fused interacting partners to force their association, or require coexpression or co-refolding to produce detectable folded and fluorescent GFP. We have engineered soluble, self-associating fragments of GFP that can be used to tag and detect either soluble or insoluble proteins in living cells or cell lysates. The split GFP system is simple and does not change fusion protein solubility.}, Author = {Cabantous, St{\'e}phanie and Terwilliger, Thomas C. and Waldo, Geoffrey S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {23 Technique}, Month = {1}, Nlm_Id = {9604648}, Number = {1}, Organization = {Bioscience Division, MS-M888, Los Alamos National Laboratory, PO Box 1663, Los Alamos, New Mexico 87545, USA.}, Pages = {102-7}, Pii = {nbt1044}, Pubmed = {15580262}, Title = {Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein}, Uuid = {7FCDFD7D-101A-4310-B293-05E0F72C7158}, Volume = {23}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt1044}} @article{Cadetti:2001, Abstract = {Whole-cell patch-clamp recordings were carried out in visually identified periglomerular and external tufted cells of rat olfactory bulb. Most of the neurones showed a slowly developing hyperpolarisation- activated current with a threshold generally positive to resting potential and with a strongly voltage-dependent activation time constant. The current, identified as Ih, was sodium- and potassium- sensitive, suppressed by external caesium, and insensitive to barium. Under current-clamp conditions, perfusion with caesium induced a 10 mV hyperpolarisation and a marked reduction of the rate of low-frequency oscillations induced experimentally. It is concluded that most of the cells in the rat glomerular layer present a distinct h-current, which is tonically active at rest and which may contribute to the oscillatory behaviour of the bulbar network.}, Author = {Cadetti, L. and Belluzzi, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuroreport}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {14}, Organization = {Dipartimento di Biologia, Sezione di Fisiologia e Biofisica, and Dipartimento di Scienze Biomediche and Terapie Avanzate, Sezione di Fisiologia Umana, Universita di Ferrara, Via L. Borsari, 46, 44100 Ferrara, Italy.}, Pages = {3117-20.}, Title = {Hyperpolarisation-activated current in glomerular cells of the rat olfactory bulb}, Uuid = {0924DAA2-9357-4FF2-A87C-E0DB75D1F7A0}, Volume = {12}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11568648}} @article{Calaora:2001, Abstract = {Neuregulin 1 (Nrg-1) isoforms have been shown to influence the emergence and growth of oligodendrocytes, the CNS myelin-forming cells. We have investigated how Nrg-1 signaling of ErbB receptors specifically controls the early stages of oligodendrocyte generation from multipotential neural precursors (NPs). We show here that embryonic striatal NPs express multiple Nrg-1 transcripts and proteins as well as their specific receptors, ErbB2 and ErbB4, but not ErbB3. The major isoform synthesized by striatal NPs is a transmembrane type III isoform called cysteine-rich domain Nrg-1. To examine the biological effect of Nrg-1, we added soluble ErbB3 (sErbB3) to growing neurospheres. This inhibitor of Nrg-1 bioactivity decreased mitosis of NPs and increased their apoptosis, resulting in a significant reduction in neurosphere size and number. When NPs were induced to migrate and differentiate by adhesion of neurospheres to the substratum, the level of type III isoforms detected by RT-PCR and Western blot decreased in parallel with a reduction in Nrg-1 fluorescence intensity in differentiating astrocytes, neurons, and oligodendrocytes. Pretreatment of growing neurospheres with sErbB3 induced a threefold increase in the proportion of oligodendrocytes generated from NPs migrating out of the neurosphere. This effect was not observed with an unrelated soluble receptor. Addition of sErbB3 during NP growth and differentiation enhanced oligodendrocyte maturation as shown by expression of galactocerebroside and myelin basic protein. We propose that both type III Nrg-1 signaling and soluble ErbB receptors modulate oligodendrocyte development from NPs.}, Author = {Calaora, V. and Rogister, B. and Bismuth, K. and Murray, K. and Brandt, H. and Leprince, P. and Marchionni, M. and Dubois-Dalcq, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Protein Isoforms/antagonists &inhibitors/metabolism/pharmacology;Cell Survival/drug effects;Cells, Cultured;Neurons/cytology/*metabolism;Rats;Signal Transduction/*physiology;Apoptosis;Receptor, erbB-3/metabolism;Chromones;Animal;Cell Division/drug effects/physiology;Mice, Inbred C57BL;Neuregulin-1/antagonists &inhibitors/*metabolism/pharmacology;Receptor, Epidermal Growth Factor/metabolism;Spinal Cord/cytology/embryology/metabolism;Support, Non-U.S. Gov't;Oligodendroglia/cytology/*metabolism;Astrocytes/cytology/metabolism;Glycosides;C;04 Adult neurogenesis factors;Stem Cells/cytology/drug effects/*metabolism;Cell Differentiation/drug effects/physiology;Mice;Cell Adhesion/physiology;Receptor, erbB-2/metabolism;Corpus Striatum/cytology/embryology/metabolism;Cell Movement/physiology;Mitosis/drug effects}, Number = {13}, Organization = {Neurovirologie et Regeneration du Systeme Nerveux, Institut Pasteur, 75724 Paris, France.}, Pages = {4740-51.}, Title = {Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro}, Uuid = {E93154B8-830A-4369-A314-2820FBBB3370}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11425901%20http://www.jneurosci.org/cgi/content/full/21/13/4740%20http://www.jneurosci.org/cgi/content/abstract/21/13/4740}} @article{Calcagnotto:2002, Abstract = {Children with brain malformations often exhibit an intractable form of epilepsy. Although alterations in cellular physiology and abnormal histology associated with brain malformations has been studied extensively, synaptic function in malformed brain regions remains poorly understood. We used an animal model, rats exposed to methylazoxymethanol (MAM) in utero, featuring loss of lamination and distinct nodular heterotopia to examine inhibitory synaptic function in the malformed brain. Previous in vitro and in vivo studies demonstrated an enhanced susceptibility to seizure activity and neuronal hyperexcitability in these animals. Here we demonstrate that inhibitory synaptic function is enhanced in rats exposed to MAM in utero. Using in vitro hippocampal slices and whole-cell voltage-clamp recordings from visualized neurons, we observed a dramatic prolongation of GABAergic IPSCs onto heterotopic neurons. Spontaneous IPSC decay time constants were increased by 195\%and evoked IPSC decay time constants by 220\%compared with age-matched control CA1 pyramidal cells; no change in IPSC amplitude or rise time was observed. GABA transport inhibitors (tiagabine and NO-711) prolonged evoked IPSC decay kinetics of control CA1 pyramidal cells (or normotopic cells) but had no effect on heterotopic neurons. Immunohistochemical staining for GABA transporters (GAT-1 and GAT-3) revealed a low level of expression in heterotopic cell regions, suggesting a reduced ability for GABA reuptake at these synapses. Together, our data demonstrate that GABA-mediated synaptic function at heterotopic synapses is altered and suggests that inhibitory systems are enhanced in the malformed brain.}, Author = {Calcagnotto, Maria Elisa and Paredes, Mercedes F. and Baraban, Scott C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:41 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {GABA Plasma Membrane Transport Proteins;Methylazoxymethanol Acetate;Epilepsy;Disease Models, Animal;24 Pubmed search results 2008;Neural Inhibition;Male;Organic Anion Transporters;Animals;Hippocampus;Research Support, U.S. Gov't, P.H.S.;In Vitro;Pregnancy;Synapses;21 Epilepsy;gamma-Aminobutyric Acid;Prenatal Exposure Delayed Effects;21 Dysplasia-heterotopia;Rats, Sprague-Dawley;Carrier Proteins;Nervous System Malformations;Rats;Patch-Clamp Techniques;Female;Membrane Proteins;Membrane Transport Proteins;21 Neurophysiology;Research Support, Non-U.S. Gov't;Neurons;Choristoma}, Medline = {22184315}, Month = {9}, Nlm_Id = {8102140}, Number = {17}, Organization = {Epilepsy Research Laboratory, Department of Neurological Surgery and The Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, California 94143, USA.}, Pages = {7596-605}, Pii = {22/17/7596}, Pubmed = {12196583}, Title = {Heterotopic neurons with altered inhibitory synaptic function in an animal model of malformation-associated epilepsy}, Uuid = {A9FEC1D3-6230-4FB6-AA51-22810514DDC5}, Volume = {22}, Year = {2002}, url = {papers/Calcagnotto_JNeurosci2002.pdf}} @article{Calcagnotto:2005, Abstract = {Focal cortical dysplasia (FCD) is a common and important cause of medically intractable epilepsy. In patients with temporal lobe epilepsy and in several animal models, compromised neuronal inhibition, mediated by GABA, contributes to seizure genesis. Although reduction in GABAergic interneuron density has been reported in FCD tissue samples, there is little available information on the resulting physiological changes in synaptic inhibition and the potential contribution of these changes to epileptogenesis in the dysplastic human brain. Using visualized whole-cell patch-clamp recordings from identified neurons in tissue slices obtained from patients with FCD, we demonstrate that GABAA-receptor-mediated inhibition is substantially altered in regions of dysplasia. These alterations include a significant reduction in IPSC frequency and a potentially compensatory decrease in transporter-mediated GABA reuptake function; the latter is marked by a significant increase in the decay-time constant for evoked and spontaneous IPSCs and a lack of effect of the GABA transport-inhibitor 1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride on IPSC kinetics. Immunohistochemical staining revealed a scattering of GABAergic interneurons across dysplastic cortex and striking reductions in GABA transporter expression. Together, these results suggest that profound alterations in GABA-mediated synaptic inhibition play an essential role in the process of epileptogenesis in patients with FCD.}, Author = {Calcagnotto, Maria Elisa and Paredes, Mercedes F. and Tihan, Tarik and Barbaro, Nicholas M. and Baraban, Scott C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Epilepsy;Synapses;21 Dysplasia-heterotopia;21 Neurophysiology;Adolescent;Adult;Comparative Study;Research Support, U.S. Gov't, P.H.S.;Neural Inhibition;Neocortex;Research Support, N.I.H., Extramural;Synaptic Transmission;Humans;24 Pubmed search results 2008;21 Epilepsy}, Month = {10}, Nlm_Id = {8102140}, Number = {42}, Organization = {Department of Neurological Surgery, University of California, San Francisco, California 94143, USA.}, Pages = {9649-57}, Pii = {25/42/9649}, Pubmed = {16237169}, Title = {Dysfunction of synaptic inhibition in epilepsy associated with focal cortical dysplasia}, Uuid = {C0C494E7-3162-408C-A346-16B0A19255F9}, Volume = {25}, Year = {2005}, url = {papers/Calcagnotto_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2687-05.2005}} @article{Calegari:2005, Abstract = {During embryonic development of the mammalian brain, the average cell-cycle length of progenitor cells in the ventricular zone is known to increase. However, for any given region of the developing cortex and stage of neurogenesis, the length of the cell cycle is thought to be similar in the two coexisting subpopulations of progenitors [i.e., those undergoing (symmetric) proliferative divisions and those undergoing (either asymmetric or symmetric) neuron-generating divisions]. Using cumulative bromodeoxyuridine labeling of Tis21-green fluorescent protein knock-in mouse embryos, in which these two subpopulations of progenitors can be distinguished in vivo, we now show that at the onset as well as advanced stages of telencephalic neurogenesis, progenitors undergoing neuron-generating divisions are characterized by a significantly longer cell cycle than progenitors undergoing proliferative divisions. In addition, we find that the recently characterized neuronal progenitors dividing at the basal side of the ventricular zone and in the subventricular zone have a longer G(2) phase than those dividing at the ventricular surface. These findings are consistent with the hypothesis (Calegari and Huttner, 2003) that cell-cycle lengthening can causally contribute to neural progenitors switching from proliferative to neuron-generating divisions and may have important implications for the expansion of somatic stem cells in general.}, Author = {Calegari, Federico and Haubensak, Wulf and Haffner, Christiane and Huttner, Wieland B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {8102140}, Number = {28}, Organization = {Max Planck Institute of Molecular Cell Biology and Genetics, D-01307 Dresden, Germany.}, Pages = {6533-8}, Pii = {25/28/6533}, Pubmed = {16014714}, Title = {Selective lengthening of the cell cycle in the neurogenic subpopulation of neural progenitor cells during mouse brain development}, Uuid = {129C72CB-6B43-45CB-86BC-137755F1CD36}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0778-05.2005}} @article{Callaway:2002, Abstract = {Recent technological advances have enabled the use of different optical methods to activate neurons, including 'caged' glutamate, photoactivation of genetically engineered cascades, and direct two-photon excitation. The ability to use light as a stimulation tool provides, in principle, a non-invasive method for the temporally and spatially precise activation of any neuron or any part of a neuron. When combined with two-photon excitation, excellent spatial control can be achieved even in complex and highly scattering preparations, such as living nervous tissue. Different methods that have been developed in the last several decades have been used to probe neuronal sensitivity, mimic synaptic input, and elucidate patterns of neural connectivity.}, Author = {Callaway, Edward M. and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Glutamates;Photic Stimulation;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;21 Calcium imaging;Brain Mapping;Animals;Light;24 Pubmed search results 2008;Neurons;review}, Medline = {22252824}, Month = {10}, Nlm_Id = {9111376}, Number = {5}, Organization = {The Salk Institute for Biological Studies, Systems Neurobiology Laboratories, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. callaway\@salk.edu}, Pages = {587-92}, Pii = {S0959438802003641}, Pubmed = {12367640}, Title = {Stimulating neurons with light}, Uuid = {4A2D5368-AB38-4818-A318-E9AA3EA45E31}, Volume = {12}, Year = {2002}, url = {papers/Callaway_CurrOpinNeurobiol2002.pdf}} @article{Callaway:1998, Abstract = {Previous studies have demonstrated that axonal arbors specific for the four main cortical layers - 2/3, 4, 5, and 6 - develop precisely from the outset using activity-independent cues. In macaque primary visual cortex (V1), layer 2/3 is subdivided into layers named 2/3A, 3B, 4A, and 4B, and layer 4 is subdivided into 4Calpha and 4Cbeta. Individual neurons in V1 of mature macaques have axonal arbors that are highly specific for these sublayers. We have studied the prenatal development of laminar and sublaminar specificity of local circuits in macaque V1. Two-hundred thirty-eight neurons were labeled intracellularly in living brain slices prepared from V1 of five prenatal macaque monkeys aged 100 to 145 d postconception (E100-E145). Axonal and dendritic arbors of labeled neurons were reconstructed to assess their relationships to the cortical layers. We find that developing spiny neurons in layers 2-4B and layer 5 specifically target superficial and deep layers without forming "incorrect" branches in layer 4C. Similarly, layer 6 pyramidal neurons that target layer 4C do not form "incorrect" branches in layer 5. These results indicate that specific projections to the main cortical layers develop with a high degree of selectivity, as in other species. However, the development of sublayer-specific projections was not always precise from the outset. Unlike postnatal animals, axons of some prenatal layer 4Cbeta spiny neurons branch in layer 4B. At similar ages, many pyramidal neurons in the upper half of layer 6 have axonal branches in layer 4Calpha as well as 4Cbeta; these projections are specific for 4Cbeta in more mature animals. Also, there is similar "exuberance" in axonal arbors of other layer 6 cell types. Transient projections were also observed in the subplate and to the white matter for cells from all layers, except 4Cbeta. These observations indicate that at least some sublayer-specific projections emerge by elimination of exuberant axonal branches and suggest that they may use activity-dependent mechanisms to identify "correct" target layers. Such cues could be provided by laminar differences in the patterns of spontaneous prenatal activity in the retino-geniculo-cortical network.}, Author = {Callaway, E. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Cell Aging;10 Development;Animals;10 Structural plasticity;Beta;Macaca radiata;Synaptic Transmission;Embryo and Fetal Development;Axons;Macaca;Visual Pathways;Pyramidal Cells;Embryo;10 Spiny stellate;Neurons;Support, U.S. Gov't, P.H.S.;Visual Cortex;Macaca nemestrina}, Medline = {98122905}, Month = {2}, Nlm_Id = {8102140}, Number = {4}, Organization = {Systems Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {1505-27}, Pubmed = {9454858}, Title = {Prenatal development of layer-specific local circuits in primary visual cortex of the macaque monkey}, Uuid = {A1B1C3C4-446E-47F2-A39C-72DA60CEC8A9}, Volume = {18}, Year = {1998}, url = {papers/Callaway_JNeurosci1998.pdf}} @article{Calmels:2005, Abstract = {Recent reports linking insertional activation of LMO2 following gene therapy for X-linked severe combined immunodeficiency (X-SCID) have led to a re-evaluation of risks following gene therapy with retroviral vectors. In our analysis of 702 integration sites in rhesus macaques that underwent transplantation up to 7 years earlier with autologous CD34+ cells transduced with amphotropic murine leukemia virus (MLV)-derived retroviral vectors containing marker genes, we detected insertion into one locus, the Mds1/Evi1 region, a total of 14 times in 9 animals. Mds1/Evi1 integrations were observed stably long term, primarily in myeloid cells. We hypothesize that this over-representation likely results from an impact on the self-renewal and engraftment potential of CD34+ progenitor cells via insertional mutagenesis at this specific locus. There is no evidence of ongoing in vivo clonal expansion of the Mds1/Evi1 populations, and all animals are hematologically normal without evidence for leukemia. Characterization of integration sites in this relevant preclinical model provides critical information for gene therapy risk assessment as well as identification of genes controlling hematopoiesis.}, Author = {Calmels, Boris and Ferguson, Cole and Laukkanen, Mikko O. and Adler, Rima and Faulhaber, Marion and Kim, Hyeoung-Joon J. and Sellers, Stephanie and Hematti, Peiman and Schmidt, Manfred and von Kalle, Christof and Akagi, Keiko and Donahue, Robert E. and Dunbar, Cynthia E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Transcription Factors;Disease Progression;Animals;DNA-Binding Proteins;Humans;Granulocytes;Leukemia;15 Retrovirus mechanism;Antigens, CD34;Retroviridae;Time Factors;Genetic Vectors;Leukocytes, Mononuclear;Leukemia Virus, Murine;Macaca mulatta;Hematopoiesis;Gene Therapy;Risk;Proto-Oncogenes;Hematopoietic Stem Cells;22 Stem cells;24 Pubmed search results 2008;Stem Cells;Primates;Mutagenesis, Insertional}, Month = {10}, Nlm_Id = {7603509}, Number = {7}, Organization = {Hematology Branch, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.}, Pages = {2530-3}, Pii = {2005-03-1115}, Pubmed = {15933056}, Title = {Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells}, Uuid = {FCBDF24F-9ED2-4AC9-85ED-ACDF048F06FF}, Volume = {106}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood-2005-03-1115}} @article{Calof:1998, Abstract = {The vertebrate olfactory epithelium (OE) is a system in which behavior of neuronal progenitor cells can be observed and manipulated easily. It is morphologically and functionally similar to embryonic germinal neuroepithelia, but is simpler in that it produces large numbers of a single type of neuron, the olfactory receptor neuron (ORN). The OE is amenable to tissue culture, gene transfer, and in vivo surgical approaches, and these have been exploited in experiments aimed at understanding the characteristics of OE neuronal progenitor cells. This has led to the realization that the ORN lineage contains at least three distinct stages of proliferating neuronal progenitor cells (including a stem cell), each of which represents a point at which growth control can be exerted. Neurogenesis proceeds continually in the OE, and studies in vivo have shown that this is a regulated process that serves to maintain the number of ORNs at a particular level. These studies suggest that OE neuronal progenitors-which are in close physical proximity to ORNs-can "read"the number of differentiated neurons in their environment and regulate production of new neurons accordingly. Putative neuronal stem cells of the OE have been identified in vitro, and studies of these cells indicate that ORNs produce a signal that feeds back to inhibit neurogenesis. This inhibitory signal may be exerted at the level of the stem cell itself. Recent studies to identify this signal, as well as endogenous stimulatory signals that may be important in regulating OE neurogenesis, are also discussed.}, Author = {Calof, A. L. and Mumm, J. S. and Rim, P. C. and Shou, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurobiol}, Keywords = {Neurons/*physiology;I;Cell Division/physiology;Cell Line/physiology;Animal;Cell Communication/physiology;Support, U.S. Gov't, P.H.S.;Olfactory Mucosa/*cytology;Support, Non-U.S. Gov't;13 Olfactory bulb anatomy;Stem Cells/*physiology}, Number = {2}, Organization = {Department of Anatomy and Neurobiology and the Developmental Biology Center, University of California, Irvine, College of Medicine, 92697- 1275, USA.}, Pages = {190-205.}, Title = {The neuronal stem cell of the olfactory epithelium}, Uuid = {7E0CB235-A148-44E4-9157-E74A14050C75}, Volume = {36}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9712304}} @article{Calvo:2000, Abstract = {The immunohistochemical detection of bromodeoxyuridine (BrdU) was used to study the cell proliferation in the developing rat pineal gland, from the appearance of pineal primordium in the embryonic day 15 (E15) until 30 days after birth. The results showed three different proliferative phases. From E15 to E21, the pineal gland shows a phase of rapid proliferation. The second phase corresponds to the first postnatal week, in which the number of labeled cells per surface unit decreases suddenly to values between 20\%to 10\%of those of embryonic period. From the second postnatal week onwards, the number of BrdU-positive cells progressively decreases.}, Author = {Calvo, J. L. and Boya, J. and Carbonell, A. L. and Garc{\'\i}a-Mauri\~{n}o, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0213-3911}, Journal = {Histol Histopathol}, Keywords = {Thymidine;Research Support, Non-U.S. Gov't;Pineal Gland;Rats;Immunohistochemistry;DNA;Female;Rats, Wistar;Cell Division;Antimetabolites;Animals;24 Pubmed search results 2008;Bromodeoxyuridine}, Medline = {20458233}, Month = {10}, Nlm_Id = {8609357}, Number = {4}, Organization = {Department of Histology, Faculty of Medicine, Complutense University, Madrid, Spain.}, Pages = {1005-10}, Pubmed = {11005223}, Title = {Cell proliferation in the developing rat pineal gland. A bromodeoxyuridine immunohistochemical study}, Uuid = {A5D89977-6DBD-4E18-901F-AD1BC3B6740D}, Volume = {15}, Year = {2000}} @article{Cam:2008, Abstract = {Transposable elements and their remnants constitute a substantial fraction of eukaryotic genomes. Host genomes have evolved defence mechanisms, including chromatin modifications and RNA interference, to regulate transposable elements. Here we describe a genome surveillance mechanism for retrotransposons by transposase-derived centromeric protein CENP-B homologues of the fission yeast Schizosaccharomyces pombe. CENP-B homologues of S. pombe localize at and recruit histone deacetylases to silence Tf2 retrotransposons. CENP-Bs also repress solo long terminal repeats (LTRs) and LTR-associated genes. Tf2 elements are clustered into 'Tf' bodies, the organization of which depends on CENP-Bs that display discrete nuclear structures. Furthermore, CENP-Bs prevent an 'extinct' Tf1 retrotransposon from re-entering the host genome by blocking its recombination with extant Tf2, and silence and immobilize a Tf1 integrant that becomes sequestered into Tf bodies. Our results reveal a probable ancient retrotransposon surveillance pathway important for host genome integrity, and highlight potential conflicts between DNA transposons and retrotransposons, major transposable elements believed to have greatly moulded the evolution of genomes.}, Author = {Cam, Hugh P. and Noma, Ken-ichi and Ebina, Hirotaka and Levin, Henry L. and Grewal, Shiv I. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Cell Cycle Proteins;Centromere Protein B;DNA-Binding Proteins;Schizosaccharomyces pombe Proteins;Genomic Instability;Genes, Mating Type, Fungal;Protein Transport;Evolution, Molecular;Histone Deacetylases;research support, n.i.h., intramural;15 Retrovirus mechanism;Heterochromatin;Gene Expression Regulation, Fungal;Oxidative Stress;DNA Transposable Elements;Genome, Fungal;21 Neurophysiology;Gene Silencing;21 Activity-development;Retroelements;24 Pubmed search results 2008;Genes, Fungal;Terminal Repeat Sequences;15 ERVs retroelements;Schizosaccharomyces}, Month = {1}, Nlm_Id = {0410462}, Number = {7177}, Organization = {Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, Maryland 20892, USA.}, Pages = {431-6}, Pii = {nature06499}, Pubmed = {18094683}, Title = {Host genome surveillance for retrotransposons by transposon-derived proteins}, Uuid = {D7343506-EFD6-4B88-AEEB-C552C324D4DD}, Volume = {451}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06499}} @article{Cameron:1998, Abstract = {The generation of neurons and glia in the developing nervous system is likely to be regulated by extrinsic factors, including growth factors and neurotransmitters. Evidence from in vivo and/or in vitro systems indicates that basic fibroblast growth factor, transforming growth factor (TGF)-alpha, insulin-like growth factor-1, and the monoamine neurotransmitters act to increase proliferation of neural precursors. Conversely, glutamate, gamma-aminobutyric acid, and opioid peptides are likely to play a role in down-regulating proliferation in the developing nervous system. Several other factors, including the neuropeptides vasoactive intestinal peptide and pituitary adenylate cyclase-activating peptide, as well as the growth factors platelet- derived growth factor, ciliary neurotrophic factor, and members of the TGF-beta family, have different effects on proliferation and differentiation depending on the system examined. Expression of many of these factors and their receptors in germinal regions of the central nervous system suggests that they can act directly on precursor populations to control their proliferation. Together, the findings discussed here indicate that proliferation and cell fate determination in the developing brain are regulated extrinsically by complex interactions between a relatively large number of growth factors and neurotransmitters.}, Author = {Cameron, H. A. and Hazel, T. G. and McKay, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurobiol}, Keywords = {C;Human;Brain/*growth &development;Growth Substances/*physiology;Aging/physiology;Animal;04 Adult neurogenesis factors;Neurotransmitters/*physiology;Animals, Newborn/growth &development}, Number = {2}, Organization = {Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.}, Pages = {287-306.}, Title = {Regulation of neurogenesis by growth factors and neurotransmitters}, Uuid = {D6B56B84-061B-4CD1-82D2-10EB4D0B952E}, Volume = {36}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9712310}} @article{Cameron:1995, Abstract = {The effects of afferent input and N-methyl-D-aspartate (NMDA) receptor activation on neurogenesis were examined in an intact system, the rat dentate gyrus, where neurons are naturally born in the adult. In the adult dentate gyrus, activation of NMDA receptors rapidly decreased the number of cells synthesizing DNA, whereas blockade of NMDA receptors rapidly increased the number of cells in the S phase identified with 3H- thymidine. Acute treatment with NMDA receptor antagonists increased the birth of neurons and increased the overall density of neurons in the granule cell layer. Lesion of the entorhinal cortex, the main excitatory afferent population to the granule neurons, also increased the birth of cells in the dentate gyrus. These results suggest that adult neurogenesis in the dentate gyrus of the rat is altered by afferent input, via NMDA receptors, and may be regulated naturally by endogenous excitatory amino acids.}, Author = {Cameron, H. A. and McEwen, B. S. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Neurosci}, Keywords = {Hippocampus/cytology/drug effects/*physiology;Dizocilpine Maleate/pharmacology;Cell Survival/drug effects;Neurons/cytology/drug effects/*physiology;Rats;Thymidine/metabolism;2-Amino-5-phosphonovalerate/analogs &derivatives/pharmacology;Receptors, N-Methyl-D-Aspartate/antagonists &inhibitors/*physiology;Homeostasis;Rats, Sprague-Dawley;Animal;Male;Time Factors;D-3;DNA/biosynthesis;Support, Non-U.S. Gov't;Afferent Pathways/*physiology;06 Adult neurogenesis injury induced;*Cell Division/drug effects;Support, U.S. Gov't, P.H.S.;S Phase;N-Methylaspartate/*pharmacology}, Number = {6}, Organization = {Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021, USA.}, Pages = {4687-92.}, Title = {Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus}, Uuid = {B2B080AD-6774-44C6-9A10-29B531BCEE8D}, Volume = {15}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7790933}} @article{Cameron:1999, Abstract = {The production of hippocampal granule neurons continues throughout adulthood but dramatically decreases in old age. Here we show that reducing corticosteroid levels in aged rats restored the rate of cell proliferation, resulting in increased numbers of new granule neurons. This result indicates that the neuronal precursor population in the dentate gyrus remains stable into old age, but that neurogenesis is normally slowed by high levels of corticosteroids. The findings further suggest that decreased neurogenesis may contribute to age-related memory deficits associated with high corticosteroids, and that these deficits may be reversible.}, Author = {Cameron, H. A. and McKay, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Nat Neurosci}, Keywords = {Neurons/*physiology;DNA/biosynthesis;Rats, Sprague-Dawley;Hippocampus/cytology/*physiology;Cell Division/physiology;Cell Survival/physiology;Rats;Adrenal Glands/physiology;Adrenal Cortex Hormones/physiology;Biological Markers;Animal;Aging/*physiology;04 Adult neurogenesis factors;Bromodeoxyuridine;Adrenalectomy;C abstr}, Number = {10}, Organization = {Laboratory of Molecular Biology, National Institutes of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. cameron\@codon.nih.gov}, Pages = {894-7.}, Title = {Restoring production of hippocampal neurons in old age}, Uuid = {7DC9E7B6-4ED4-46F0-A2A5-8B59E943237F}, Volume = {2}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10491610%20http://library.neurosci.nature.com/server-java/Propub/neuro/nn1099_894.fulltext%20http://library.neurosci.nature.com/server-java/Propub/neuro/nn1099_894.abstract}} @article{Cameron:1993, Abstract = {In order to determine whether newly born cells in the dentate gyrus of the adult rat express the neuronal marker, neuron-specific enolase, or the glial marker, glial fibrillary acidic protein, we performed combined immunohistochemistry and autoradiography on brains from adult rats perfused at various times ranging from 1 h to four weeks following [3H]thymidine administration. Light-microscopic examination revealed a negligible number of [3H]thymidine-labeled cells showing neuron- specific enolase immunoreactivity during mitosis. However, by two weeks after [3H]thymidine administration, a significant increase in the density of [3H]thymidine-labeled neuron-specific enolase-immunoreactive cells was detected. Three weeks following [3H]thymidine injection the majority of [3H]thymidine-labeled cells (>70\%) were immunoreactive for the neuronal marker. At the four-week time-point, [3H]thymidine-labeled neuron-specific enolase-immunoreactive cells were indistinguishable from neighboring granule cells. In contrast, glial fibrillary acidic protein immunoreactivity was observed in a small but significant number of [3H]thymidine cells at the 1-h time-point and the proportion of labeled cells that were immunoreactive for this cell marker did not increase with time. [3H]Thymidine-labeled cells that were immunoreactive for glial fibrillary acidic protein typically showed morphologic characteristics of radial glia at all time-points. At the 1- h time-point, the majority of [3H]thymidine-labeled cells were observed in the hilus (>60\%) with the remainder being located in the granule cell layer. However, with a four-week survival-time most [3H]thymidine- labeled cells (>85\%) were located in the granule cell layer. The majority of newly born cells in the adult dentate gyrus differentiate into neurons.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Cameron, H. A. and Woolley, C. S. and McEwen, B. S. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuroscience}, Keywords = {Cell Aging;Rats;Comparative Study;A-5;Neuroglia/chemistry/*cytology;Animal;Cell Movement;Rats, Sprague-Dawley;Phosphopyruvate Hydratase/*analysis;Neurons/*cytology/enzymology;Male;Support, Non-U.S. Gov't;Glial Fibrillary Acidic Protein/*analysis;Support, U.S. Gov't, P.H.S.;Cell Division;Biological Markers;Hippocampus/*cytology;Nerve Tissue Proteins/*analysis}, Number = {2}, Organization = {Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.}, Pages = {337-44.}, Title = {Differentiation of newly born neurons and glia in the dentate gyrus of the adult rat}, Uuid = {9FB6E0A6-67A7-11DA-A4B6-000D9346EC2A}, Volume = {56}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8247264}} @article{Cameron:1994, Abstract = {The dentate gyrus of the rat produces new granule neurons well into adulthood. In the adult, newly born granule neurons migrate from the hilus to the granule cell layer, receive synaptic input, extend axons into the mossy fiber pathway, and express a neuronal marker. No previous studies have identified factors that regulate neuronal birth in the adult dentate gyrus. In order to determine whether glucocorticoids control neurogenesis in the adult dentate gyrus, the effects of adrenal steroid manipulations on neuronal birth were assessed using [3H]thymidine autoradiography and immunohistochemistry for the neuronal marker neuron specific enolase. Acute treatment with corticosterone produced a significant decrease in the density of [3H]thymidine-labeled cells in the hilus of the dentate gyrus. In contrast, removal of endogenous adrenal steroids stimulated increased neuronal birth; adrenalectomy resulted in a significant increase in the number of neuron specific enolase-immunoreactive [3H]thymidine labeled cells in the granule cell layer compared to sham operation. Replacement of corticosterone to adrenalectomized rats after [3H]thymidine injection did not substantially alter the increase in neurogenesis observed following adrenalectomy, even though this replacement protects cells from adrenalectomy-induced cell death. These results indicate that the rate of neurogenesis in the dentate gyrus of the adult rat is dependent upon the levels of circulating adrenal steroids.}, Author = {Cameron, H. A. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {Neuroscience}, Keywords = {Hippocampus/cytology/drug effects/*physiology;Cell Differentiation;Corticosterone/pharmacology/*physiology;Rats;Apoptosis/*physiology;Animal;Rats, Sprague-Dawley;Stem Cells/*cytology/drug effects;DNA Replication;C abstr;Male;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Phosphopyruvate Hydratase/analysis;*Adrenalectomy;Biological Markers;Neurons/*cytology/drug effects;Cell Division/drug effects}, Number = {2}, Organization = {Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021.}, Pages = {203-9.}, Title = {Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus}, Uuid = {E67201A2-2FA3-4A82-B5D9-F28E4425C54B}, Volume = {61}, Year = {1994}, url = {papers/Cameron_Neuroscience1994}} @article{Cameron:1998a, Abstract = {Adrenal steroids and N-methyl-D-aspartate receptor activation have both been shown to regulate the rate of proliferation of granule neuron progenitor cells in the dentate gyrus of adult rats [Cameron H. A. and Gould E. (1994) Neuroscience 61, 203-209; Cameron H. A. et al. (1995) J. Neurosci. 15, 46874692]. Parallels between the actions of these two factors suggest that they may regulate cell division through a common pathway. This hypothesis was tested by altering both of the factors simultaneously and determining whether the effects were additive. The results of this study demonstrate that alterations in N-methyl-D- aspartate receptor activation block the effects of corticosterone level on cell proliferation; N-methyl-D-aspartate blocks the adrenalectomy- induced increase in [3H]thymidine-labelled cell density in the dentate gyrus, whereas the N-methyl-D-aspartate receptor antagonist dizocilpine maleate (MK-801) prevents the corticosterone-induced decrease in proliferating cells. This finding suggests that adrenal steroids and N- methyl-D-aspartate receptor activation regulate granule cell production in the adult rat dentate gyrus through a common pathway and that N- methyl-D-aspartate receptor activation operates downstream of corticosterone in this pathway.}, Author = {Cameron, H. A. and Tanapat, P. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuroscience}, Keywords = {Dizocilpine Maleate/pharmacology;Rats;Corticosterone/metabolism;Excitatory Amino Acid Antagonists/pharmacology;Animal;Adrenalectomy;Rats, Sprague-Dawley;C abstr;Biotransformation/physiology;Male;Adrenal Cortex Hormones/*physiology;Support, Non-U.S. Gov't;inhibitors/*physiology;Cell Division/physiology;Dentate Gyrus/*cytology/*physiology;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Receptors, N-Methyl-D-Aspartate/agonists/antagonists &;Neurons/physiology}, Number = {2}, Organization = {Laboratory of Neuroendocrinology, Rockefeller University, New York, NY 10021, USA.}, Pages = {349-54.}, Title = {Adrenal steroids and N-methyl-D-aspartate receptor activation regulate neurogenesis in the dentate gyrus of adult rats through a common pathway}, Uuid = {60B3B25D-3B50-4114-9F6F-6A2F75310409}, Volume = {82}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9466447}} @article{Caminiti:1999, Abstract = {The ipsilateral association connections of the cortex of the dorsal part of the rostral bank of the parieto-occipital sulcus and of the adjoining posterior part of the superior parietal lobule were studied by using different retrograde fluorescent tracers. Fluoro-Ruby, Fast blue and Diamidino yellow were injected into visual area V6A, and dorso-caudal (PMdc, F2) and dorso-rostral (PMdr, F7) premotor cortex, respectively. The parietal area of injection had been previously characterized physiologically in behaving monkeys, through a variety of oculomotor and visuomanual tasks. Area V6A is mainly linked by reciprocal projections to parietal areas 7m, MIP (medial intraparietal) and PEa, and, to a lesser extent, to frontal areas PMdr (rostral dorsal premotor cortex, F7) and PMdc (F2). All these areas project to that part of the dorsocaudal premotor cortex that has a direct access to primary motor cortex. V6A is also connected to area F5 and, to a lesser extent, to 7a, ventral (VIP) and lateral (LIP) intraparietal areas. This pattern of association connections may explain the presence of visually-related and eye-position signals in premotor cortex, as well as the influence of information concerning arm position and movement direction on V6A neural activity. Area V6A emerges as a potential 'early' node of the distributed network underlying visually-guided reaching. In this network, reciprocal association connections probably impose, through re-entrant signalling, a recursive property to the operations leading to the composition of eye and hand motor commands.}, Author = {Caminiti, R. and Genovesio, A. and Marconi, B. and Mayer, A. B. and Onorati, P. and Ferraina, S. and Mitsuda, T. and Giannetti, S. and Squatrito, S. and Maioli, M. G. and Molinari, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Oculomotor Muscles;Research Support, Non-U.S. Gov't;Movement;Macaca mulatta;Motor Cortex;Space Perception;Neural Pathways;Occipital Lobe;Parietal Lobe;Histocytochemistry;Brain Mapping;Animals;24 Pubmed search results 2008;Hand Strength;Frontal Lobe}, Medline = {99440155}, Month = {9}, Nlm_Id = {8918110}, Number = {9}, Organization = {Istituto di Fisiologia umana, Universit\`{a} di Roma La Sapienza, Rome, Italy. caminitir\@axrma.uniroma1.it}, Pages = {3339-45}, Pii = {ejn801}, Pubmed = {10510199}, Title = {Early coding of reaching: frontal and parietal association connections of parieto-occipital cortex}, Uuid = {96515AAE-E939-4602-B434-C841B139F8F1}, Volume = {11}, Year = {1999}} @article{Caminiti:1979, Abstract = {Horseradish peroxidase (HRP) was injected into the first (SI) or second (SII) somatosensory areas of 21 adult cats. The radial and tangential (normal and parallel to the pial surface, respectively) distribution and morphology of the callosal neurons were studied. HRP injections were combined with single unit recording in the contralateral cortex in order to determine which part of the somatosensory periphery is represented within the regions containing callosal neurons, the callosal (efferent) zones, in SI and SII. The callosal zone of SI extends over the trunk and part of the forepaw representation. In the forepaw and hindlimb representations callosal neurons projecting only to the contralateral SII are found, while in the trunk representation callosal neurons projecting to contralateral SI or SII are found. The callosal zone in SII extends widely throughout the forepaw representation in this area and projects to the contralateral SII but not to SI. In both SI and SII the callosal neurons are mainly located in layer III. A few of them are also found in layer VI. They are very rare in other layers. Callosal neurons in layer III are mostly pyramidal but exceptionally stellate; in layer VI they are pyramidal, triangular, and occasionally stellate. These data indicate that transformations of the cortical somatosensory maps are achieved in the message sent through the corpus callosum. These transformations are i) determined by the extent and location of the callosal zones and perhaps by the distribution of callosal neurons within them, ii) different in different areas, iii) different in a same area, according to the cortical targets to which they are conveyed. The existence of callosal connections originated from areas of distal forepaw representation supplies a possible anatomical substrate for those types of intermanual transfer of tactile learning which depend upon the integrity of the corpus callosum.}, Author = {Caminiti, R. and Innocenti, G. M. and Manzoni, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Dominance, Cerebral;Electric Stimulation;Hindlimb;Axonal Transport;Cats;Efferent Pathways;Not relevant;11 Glia;Evoked Potentials;Brain Mapping;Synaptic Transmission;Forelimb;Horseradish Peroxidase;Animals;Somatosensory Cortex;Neurons;Corpus Callosum}, Medline = {79169608}, Month = {4}, Nlm_Id = {0043312}, Number = {2}, Pages = {295-314}, Pubmed = {86455}, Title = {The anatomical substrate of callosal messages from SI and SII in the cat}, Uuid = {5E061307-30FA-4A92-B88F-BB70E46E3ECF}, Volume = {35}, Year = {1979}} @article{Caminiti:1981, Abstract = {The distribution of S1 (first somatosensory area) and S2 (second somatosensory area) neurons projecting to the contralateral S2 was studied with horseradish peroxidase in normal adult cats and in cats aged between 129 and 248 days in which the injected S2 area had been deprived of some of its input by an earlier lesion (on postnatal days 3 to 30; day of birth = day 1) of ipsilateral S1, alone or combined with a lesion of contralateral S2. In animals with S1 lesions, as in the normal controls, labeled neurons were selectively distributed to the regions of the trunk representation and to parts of the forelimb and hindlimb representations; however, the normally acallosal region in the forepaw representation contained scattered labeled neurons in three of the four animals whose S1 had been lesioned during the first postnatal week. In these animals, the distribution of labeled neurons in the contralateral S2 was apparently normal. Furthermore, the additional lesion of this area during the first postnatal week (one animal) did not increase the degree of filling-in of the normally acallosal parts of S1. The partial filling-in of the acallosal parts of S1 is probably due to the preservation to adulthood of some of the callosal neurons which are present in these regions during the early postnatal life. Possibly, these neurons did not disappear (or lose their callosal axons) because the neonatal lesion (i) allowed their successful competition for terminal space in contralateral S2 or (ii) induced a reorganization of the peripheral input to this area.}, Author = {Caminiti, R. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Computers;Aging;Laterality;Cats;Not relevant;11 Glia;Afferent Pathways;Somatosensory Cortex;Animals;Support, Non-U.S. Gov't;Neurons;Corpus Callosum}, Medline = {81164888}, Nlm_Id = {0043312}, Number = {1}, Pages = {53-62}, Pubmed = {7215510}, Title = {The postnatal development of somatosensory callosal connections after partial lesions of somatosensory areas}, Uuid = {3CDA37AB-3D39-4E61-938A-AAEC45F821D2}, Volume = {42}, Year = {1981}} @article{Cammer:1996, Abstract = {In the brains of adult rodents carbonic anhydrase II (CA) immunoreactivity has been observed in the choroid plexus and in oligodendrocytes, astrocytes, and myelin. Localization and functions of CA in the neonatal brain, however, have been controversial. One issue is whether the CAII-immunopositive round and ameboid cells in the corpus callosum and cingulum in the rat CNS during the first postnatal week are oligodendrocytes or microglia. Colocalization of CAII with the microglial antigen, ED1, and the microglia-specific isolectin, BSI-B4, suggested that most (approx. 60\%) of the CAII-positive round and ameboid cells in rat brain during the first postnatal week were, indeed, macrophages and microglia. During that initial week, some CAII-positive protoplasmic astrocytes (approx. 40\%) were observed as well. At the end of the first postnatal week smooth-surfaced CAII-positive cells began to appear in the corpus callosum. Those cells also bound MAbO4, a marker for the oligodendrocyte cell line. We conclude that during the first postnatal week most of the CAII-positive cells are macrophages and microglia, and that some are protoplasmic astrocytes. During the second postnatal week CAII-positive cells in the oligodendrocyte lineage become apparent, and by the end of that week there are few CAII-positive microglia. Confocal microscopy suggests that in brains of three-day-old rats the ameboid microglia are associated with nerve fibers, where they may perform phagocytosis of axons, directional guidance of axons, or disinhibition of axonal growth.}, Author = {Cammer, W. and Zhang, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Prosencephalon;Microscopy, Confocal;Rats;Neurofilament Proteins;Not relevant;Rats, Wistar;11 Glia;Antibody Specificity;Animals, Newborn;Support, U.S. Gov't, P.H.S.;Microglia;Animals;Support, Non-U.S. Gov't;Carbonic Anhydrases;Neurons;Axons}, Medline = {96337181}, Month = {7}, Nlm_Id = {8109498}, Number = {2}, Organization = {Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.}, Pages = {131-6}, Pii = {S0165572896000677}, Pubmed = {8765336}, Title = {Carbonic anhydrase II in microglia in forebrains of neonatal rats}, Uuid = {A1B54073-2C96-4DE7-BA9C-35554083F979}, Volume = {67}, Year = {1996}} @article{Campbell:2005, Abstract = {Sodium-dependent high-affinity glutamate transporters regulate synaptic glutamate levels to maintain low ambient levels of glutamate and prevent excitotoxicity. Most studies using pharmacological inhibition of glutamate transport to examine the involvement of glutamate transporters in regulating synaptic activity have examined small synaptic currents. Using in vitro brain slices, we investigated the effects of uptake inhibition on two types of epileptiform activity, bicuculline-induced paroxysmal activity, and epileptiform responses in the freeze-lesion epilepsy model. In layer II/III pyramidal cells of the prefrontal cortex, inhibiting uptake with low concentrations of DL-threo-ss-benzyloxyaspartic acid (TBOA) (20 or 30 microM) prolonged bicuculline-induced epileptiform activity. At higher concentrations, TBOA (150 or 300 microM) caused a transient enhancement of epileptiform discharges that was followed by a decrease. In the freeze-lesion model, inhibiting uptake also increased the amplitude and response area of evoked activity. The prolongation of epileptiform activity exhibited by the inhibition of glutamate uptake (TBOA 20 or 30 microM) is attributed to an increase in the level of glutamate extracellularly during uptake blockade, resulting in sustained activation of glutamate receptors. The decrease in epileptiform activity at higher TBOA concentration could be due to glutamate receptor desensitization or loss of excitability due to a depolarization block. The present results suggest that decreases in glutamate uptake can be proconvulsant in the two models of epilepsy examined.}, Author = {Campbell, Susan and Hablitz, John J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Receptors, Glutamate;Dose-Response Relationship, Drug;Animals;Prefrontal Cortex;In Vitro;Rats;21 Epilepsy;Neocortex;Aspartic Acid;Epilepsy;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Patch-Clamp Techniques;Disease Models, Animal;Amino Acid Transport System X-AG;Bicuculline;Glutamates;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;Freezing;24 Pubmed search results 2008;Research Support, N.I.H., Extramural}, Nlm_Id = {2983306R}, Organization = {Department of Neurobiology and Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.}, Pages = {129-33}, Pii = {EPI01020}, Pubmed = {15987267}, Title = {Modification of epileptiform discharges in neocortical neurons following glutamate uptake inhibition}, Uuid = {56A0358A-F987-4F39-A3DE-D1678AC6FA13}, Volume = {46 Suppl 5}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1528-1167.2005.01020.x}} @article{Campbell:2005a, Abstract = {Cortical neurogenesis is a highly stereotyped process in which progenitor cells generate neurons destined for specific cortical layers depending on the timing of cell cycle exit. Previous work has shown that during corticogenesis, progenitors become progressively restricted in their developmental potential. Recent work has uncovered some of the intrinsic mechanisms that underlie this fate restriction. In addition to timing, new studies suggest that the location of cell cycle exit in the cortical germinal zone may also contribute to cortical neuron specification.}, Author = {Campbell, Kenneth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, Ohio 45229, USA. kenneth.campbell\@chmcc.org}, Pages = {373-6}, Pii = {S0896-6273(05)00350-8}, Pubmed = {15882634}, Title = {Cortical neuron specification: it has its time and place}, Uuid = {8C13F59D-C13A-42E1-A833-0BD37DC04DB4}, Volume = {46}, Year = {2005}, url = {papers/Campbell_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.014}} @article{Campbell:2006, Abstract = {There is strong evidence for a genetic predisposition to autism and an intense interest in discovering heritable risk factors that disrupt gene function. Based on neurobiological findings and location within a chromosome 7q31 autism candidate gene region, we analyzed the gene encoding the pleiotropic MET receptor tyrosine kinase in a family based study of autism including 1,231 cases. MET signaling participates in neocortical and cerebellar growth and maturation, immune function, and gastrointestinal repair, consistent with reported medical complications in some children with autism. Here, we show genetic association (P = 0.0005) of a common C allele in the promoter region of the MET gene in 204 autism families. The allelic association at this MET variant was confirmed in a replication sample of 539 autism families (P = 0.001) and in the combined sample (P = 0.000005). Multiplex families, in which more than one child has autism, exhibited the strongest allelic association (P = 0.000007). In case-control analyses, the autism diagnosis relative risk was 2.27 (95\%confidence interval: 1.41-3.65; P = 0.0006) for the CC genotype and 1.67 (95\%confidence interval: 1.11-2.49; P = 0.012) for the CG genotype compared with the GG genotype. Functional assays showed that the C allele results in a 2-fold decrease in MET promoter activity and altered binding of specific transcription factor complexes. These data implicate reduced MET gene expression in autism susceptibility, providing evidence of a previously undescribed pathophysiological basis for this behaviorally and medically complex disorder.}, Author = {Campbell, Daniel B. and Sutcliffe, James S. and Ebert, Philip J. and Militerni, Roberto and Bravaccio, Carmela and Trillo, Simona and Elia, Maurizio and Schneider, Cindy and Melmed, Raun and Sacco, Roberto and Persico, Antonio M. and Levitt, Pat}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Transcription Factors;Receptors, Growth Factor;Humans;Base Sequence;Variation (Genetics);DNA;Female;Chromosomes, Human, Pair 7;research support, non-u.s. gov't;Male;Genetic Predisposition to Disease;Polymorphism, Single Nucleotide;Case-Control Studies;Alleles;Autistic Disorder;Genotype;research support, n.i.h., extramural;Linkage Disequilibrium;Promoter Regions (Genetics);24 Pubmed search results 2008;Chromosome Mapping;Proto-Oncogene Proteins;Transcription, Genetic}, Month = {11}, Nlm_Id = {7505876}, Number = {45}, Organization = {Department of Pharmacology, Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, TN 37203, USA.}, Pages = {16834-9}, Pii = {0605296103}, Pubmed = {17053076}, Title = {A genetic variant that disrupts MET transcription is associated with autism}, Uuid = {E148E125-B406-4E94-834E-302DDE3A3C40}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0605296103}} @article{Campos-Castello:1999, Abstract = {INTRODUCTION: A wide range of conditions are due to alterations in neurone migration (ANM). Mental retardation, motor disorders and epilepsy are seen in all these disorders. Anomalies included with the ANM are those produced at the time of neuronal migration in the phase prior to neurone proliferation and during the time following cortical organization. All these have a common characteristic, namely an anomalous cerebral cortex (cerebral dysplasias). DEVELOPMENT: There is a high incidence of epilepsy in ANM (60\%), appearing early (10\%neonatal, 42\%before 1 year old). The frequency of crises increases with age. Extended and diffused generalized forms presents as epileptic encephalopathies (Ohtahara, West, Lennox-Gastaut), whilst focal forms are seen as simple motor, partial crises, complex and secondarily generalized crises with a tendency to status epilepticus and also to continuous partial epilepsy. In diffuse, extensive forms, the EEG is characterized by large amplitude theta-delta rhythm activity (specific) with the presence of rapid activity (15-25 Hz) and of large amplitude (150-300 microV) which may also be found in other processes. In localized forms the recordings vary: localized discharges with/without crises, multifocal discharges in more than two lobes with a defined critical area, positive discharges, ipsilateral spike-and-wave complexes associated with focal discharges or with normal recordings. We review different types of ANM: in the phase of proliferation (hemimegalencephalia), the agyria-paquigyria complex; in phase of migration: type I lissencephalias (Miller-Dieker), layered heterotopias (double cortex), type II (cobblestone) lissencephalias and neuronal heterotopias, and in the phase of organization of the cortex: polymicrogyria and the esquissencephalias I and II. CONCLUSIONS: The functional prognosis in ANM depends on the control of the crises rather than on the extent of the lesion. Surgical treatment leads to 42\%good or excellent results.}, Author = {Campos-Castell{\'o}, J. and L{\'o}pez-Lafuente, A. and Ram{\'\i}rez-Segura, R. and Mart{\'\i}nez-Hern{\'a}ndez, C. and de Santos-Moreno, M. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0210-0010}, Journal = {Rev Neurol}, Keywords = {Epilepsy;21 Epilepsy;Electroencephalography;Research Support, Non-U.S. Gov't;Magnetic Resonance Imaging;21 Neurophysiology;24 Pubmed search results 2008;English Abstract;Humans;Brain;Cell Movement;review;Neurons}, Medline = {20240949}, Month = {1}, Nlm_Id = {7706841}, Organization = {Servicio de Neurolog{\'\i}a Pedi{\'a}trica, Hospital Cl{\'\i}nico Universitario San Carlos, Madrid, Espa\~{n}a.}, Pages = {S14-9}, Pubmed = {10778481}, Title = {[Epileptic signs in alterations of neuronal migration]}, Uuid = {06B0DCFF-0528-4A4D-91A6-0BC086BE453D}, Volume = {28 Suppl 1}, Year = {1999}} @article{Canaple:2003, Abstract = {Biological clocks are intrinsic time-keeping systems that regulate behavior and physiological functions in most living organisms. Recent works in this area have addressed possible molecular links between the endogenous circadian clock and cell cycle regulation. In this review, by addressing how circadian clocks can interfere with the cell cycle and how the disruption of the circadian rhythm may cause defects in regulation of cell proliferation, we highlight this potential connection between circadian rhythm and cell cycle. We also discuss how the acquisition of recent data in circadian clock mechanism may help chronotherapy, which takes into account the biological time to improve cancer treatments, and may open new therapeutic avenues for treating circadian-related diseases. 0008-5472 Journal Article Review Review, Tutorial}, Author = {Canaple, L. and Kakizawa, T. and Laudet, V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cancer Res}, Keywords = {Neoplasms/*pathology/therapy;Cell Division/physiology;10 Development;Cell Cycle/physiology;F abstr;Human;Circadian Rhythm/*physiology;Support, Non-U.S. Gov't;Animals}, Number = {22}, Organization = {Structure and Evolution of Nuclear Hormone Receptors, UMR 5665 Centre National de la Recherche Scientifique, Ecole Normale Superieure de Lyon, 46 allee d'Italie, 69364 Lyon Cedex 07, France.}, Pages = {7545-52}, Pubmed = {14633665}, Title = {The days and nights of cancer cells}, Uuid = {D8434813-7B45-4D69-9E37-5B5001DB608B}, Volume = {63}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14633665}} @article{Cancedda:2007, Abstract = {GABA exerts excitatory actions on embryonic and neonatal cortical neurons, but the in vivo function of this GABA excitation is essentially unknown. Using in utero electroporation, we eliminated the excitatory action of GABA in a subpopulation of rat ventricular progenitors and cortical neurons derived from these progenitors by premature expression of the Cl- transporter KCC2, as confirmed by the changes in the reversal potential of GABA-induced currents and the resting membrane potential after GABA(A) receptor blockade. We found that radial migration to layer II/III of the somatosensory cortex of neurons derived from the transfected progenitors was not significantly affected, but their morphological maturation was markedly impaired. Furthermore, reducing neuronal excitability of cortical neurons in vivo by overexpressing an inward-rectifying K+ channel, which lowered the resting membrane potential, mimicked the effect of premature KCC2 expression. Thus, membrane depolarization caused by early GABA excitation is critical for morphological maturation of neonatal cortical neurons in vivo.}, Author = {Cancedda, Laura and Fiumelli, Hubert and Chen, Karen and Poo, Mu-ming M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;10 Development;21 Neurophysiology;21 Activity-development;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8102140}, Number = {19}, Organization = {Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720-3200, USA.}, Pages = {5224-35}, Pii = {27/19/5224}, Pubmed = {17494709}, Title = {Excitatory GABA action is essential for morphological maturation of cortical neurons in vivo}, Uuid = {069C2760-2679-43F1-9D75-0FA39D79D01D}, Volume = {27}, Year = {2007}, url = {papers/Cancedda_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5169-06.2007}} @article{Canepari:2000, Abstract = {In the rat hippocampus, during the first postnatal week, network activity is characterized by GABA-driven giant depolarizing potentials (GDPs) associated with calcium signals that are readily blocked when the GABAA antagonist bicuculline is applied to the bath. Towards the end of the first postnatal week, in concomitance with the shift of GABA responses from the depolarizing to the hyperpolarizing direction, functional glutamatergic connections start appearing. At this developmental stage, application of bicuculline blocks GABAA-mediated inhibition and induces the appearance of interictal epileptiform discharges. In the present experiments, we have used a high spatio-temporal resolution imaging system to compare, on a time scale of tens of ms, the onset and propagation of fast calcium transients generated within a GABAergic or glutamatergic network. We found that, during the first postnatal week, calcium signals associated to evoked GDPs arise from the activation of a local circuitry of neurons spanning the stratum radiatum and the pyramidal layer. Similar activation patterns were elicited by focal application of GABA in the presence of kynurenic acid, a broad spectrum ionotropic glutamatergic antagonist, and were blocked by bicuculline. During the second postnatal week, in the presence of bicuculline, calcium signals associated with interictal discharges evoked by stimulation of glutamatergic fibres propagated along the well-defined three-synaptic pathway from the dentate gyrus to the CA1 hippocampal area.}, Author = {Canepari, M. and Mammano, F. and Kachalsky, S. G. and Rahamimoff, R. and Cherubini, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0143-4160}, Journal = {Cell Calcium}, Keywords = {gamma-Aminobutyric Acid;Fluorescent Dyes;Fluorescence;Calcium Signaling;Animals;Aniline Compounds;Rats;Glutamic Acid;Egtazic Acid;Patch-Clamp Techniques;in vitro ;Hippocampus;Rats, Wistar;Calcium;comparative study ;Bicuculline;research support, non-u.s. gov't ;21 Calcium imaging;Animals, Newborn;Nerve Net;Action Potentials;21 Neurophysiology;GABA Antagonists;Xanthenes;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8006226}, Number = {1}, Organization = {INFM Unit, International School for Advanced Studies (SISSA), Trieste, Italy.}, Pages = {25-33}, Pii = {S0143-4160(99)90086-6}, Pubmed = {10726208}, Title = {GABA- and glutamate-mediated network activity in the hippocampus of neonatal and juvenile rats revealed by fast calcium imaging}, Uuid = {0C21BC94-9A0E-4C4A-BCD6-F321062EF5B9}, Volume = {27}, Year = {2000}, url = {papers/Canepari_CellCalcium2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1054/ceca.1999.0086}} @article{Cang:2005, Abstract = {The visual cortex is organized into retinotopic maps that preserve an orderly representation of the visual world, achieved by topographically precise inputs from the lateral geniculate nucleus. We show here that geniculocortical mapping is imprecise when the waves of spontaneous activity in the retina during the first postnatal week are disrupted genetically. This anatomical mapping defect is present by postnatal day 8 and has functional consequences, as revealed by optical imaging and microelectrode recording in adults. Pharmacological disruption of these retinal waves during the first week phenocopies the mapping defect, confirming both the site and the timing of the disruption in neural activity responsible for the defect. Analysis shows that the geniculocortical miswiring is not a trivial or necessary consequence of the retinogeniculate defect. Our findings demonstrate that disrupting early spontaneous activity in the eye alters thalamic connections to the cortex.}, Author = {Cang, Jianhua and Renter{\'\i}a, Ren{\'e} C. and Kaneko, Megumi and Liu, Xiaorong and Copenhagen, David R. and Stryker, Michael P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-05-21 20:36:03 +0000}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Retina;research support, n.i.h., extramural ;Animals;Bicyclo Compounds, Heterocyclic;Synaptic Transmission;Neurons, Afferent;Nicotinic Agonists;research support, non-u.s. gov't;Time Factors;Visual Fields;research support, non-u.s. gov't ;Pyridines;Animals, Newborn;Mice, Knockout;21 Neurophysiology;21 Activity-development;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Visual Cortex;Geniculate Bodies;Receptors, Nicotinic;Brain Mapping; retinal wave paper; currOpinRvw}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {W. M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, San Francisco, California 94143, USA.}, Pages = {797-809}, Pii = {S0896-6273(05)00782-8}, Pubmed = {16337917}, Title = {Development of precise maps in visual cortex requires patterned spontaneous activity in the retina}, Uuid = {20E8EE91-0A98-44F3-93AB-3693A003874F}, Volume = {48}, Year = {2005}, url = {papers/Cang_Neuron2005a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.09.015}} @article{Cang:2005a, Abstract = {Ephrin-As and their receptors, EphAs, are expressed in the developing cortex where they may act to organize thalamic inputs. Here, we map the visual cortex (V1) in mice deficient for ephrin-A2, -A3, and -A5 functionally, using intrinsic signal optical imaging and microelectrode recording, and structurally, by anatomical tracing of thalamocortical projections. V1 is shifted medially, rotated, and compressed and its internal organization is degraded. Expressing ephrin-A5 ectopically by in utero electroporation in the lateral cortex shifts the map of V1 medially, and expression within V1 disrupts its internal organization. These findings indicate that interactions between gradients of EphA/ephrin-A in the cortex guide map formation, but that factors other than redundant ephrin-As are responsible for the remnant map. Together with earlier work on the retinogeniculate map, the current findings show that the same molecular interactions may operate at successive stages of the visual pathway to organize maps.}, Author = {Cang, Jianhua and Kaneko, Megumi and Yamada, Jena and Woods, Georgia and Stryker, Michael P. and Feldheim, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-19 11:17:24 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Aging;Embryonic Development;Retina;Mice, Knockout;Ligands;Visual Cortex;24 Pubmed search results 2008;Ephrin-A5;Ephrin-A2;research support, n.i.h., extramural;Animals, Newborn;Brain Mapping;Animals;Ephrin-A3;Mice;Synaptic Transmission;Thalamus}, Month = {11}, Nlm_Id = {8809320}, Number = {4}, Organization = {W. M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, San Francisco, California 94143, USA.}, Pages = {577-89}, Pii = {S0896-6273(05)00935-9}, Pubmed = {16301175}, Title = {Ephrin-As guide the formation of functional maps in the visual cortex}, Uuid = {FDC52C06-57DD-4770-B06B-DA02F1DD89F5}, Volume = {48}, Year = {2005}, url = {papers/Cang_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.10.026}} @article{Cang:2008, Abstract = {The topographic representation of visual space is preserved from retina to thalamus to cortex. We have previously shown that precise mapping of thalamocortical projections requires both molecular cues and structured retinal activity. To probe the interaction between these two mechanisms, we studied mice deficient in both ephrin-As and retinal waves. Functional and anatomical cortical maps in these mice were nearly abolished along the nasotemporal (azimuth) axis of the visual space. Both the structure of single-cell receptive fields and large-scale topography were severely distorted. These results demonstrate that ephrin-As and structured neuronal activity are two distinct pathways that mediate map formation in the visual cortex and together account almost completely for the formation of the azimuth map. Despite the dramatic disruption of azimuthal topography, the dorsoventral (elevation) map was relatively normal, indicating that the two axes of the cortical map are organized by separate mechanisms.}, Author = {Cang, Jianhua and Niell, Cristopher M. and Liu, Xiaorong and Pfeiffenberger, Cory and Feldheim, David A. and Stryker, Michael P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development;Visual Cortex;24 Pubmed search results 2008;research support, non-u.s. gov't;Mice, Knockout;Mice, Inbred C57BL;comparative study;research support, n.i.h., extramural;Brain Mapping;Animals;Ephrins;Mice;Visual Fields;Visual Pathways}, Month = {2}, Nlm_Id = {8809320}, Number = {4}, Organization = {W.M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.}, Pages = {511-23}, Pii = {S0896-6273(08)00028-7}, pmid = {18304481}, Title = {Selective disruption of one Cartesian axis of cortical maps and receptive fields by deficiency in ephrin-As and structured activity}, Uuid = {99B7B73B-118F-485E-A0EB-4F16ADF49DC6}, Volume = {57}, Year = {2008}, url = {papers/Cang_Neuron2008.pdf}, doi = {10.1016/j.neuron.2007.12.025}} @article{Canki:2000, Abstract = {Human immunodeficiency virus type 1 (HIV-1) has been found in the vitreous of persons with AIDS. Here we investigated the susceptibility of human retinal pigment epithelial (RPE) cells to HIV-1 infection in culture and the effects of HIV-1 on the phagocytic function of the RPE. We found that 10 of 11 populations of RPE cells isolated from different fetal or adult eyes were susceptible to low-level replication of HIV-1/NL4-3 as determined by the detection of viral DNA and spliced viral RNA encoding envelope. HIV-1 infection was not inhibited by recombinant soluble CD4, suggesting that CD4 is not required for virus entry into RPE cells. RPE cells fused with target cells constitutively expressing HIV-1 envelope glycoproteins, indicating that HIV-1 enters cells by receptor-mediated fusion. Exposure to HIV-1 or recombinant gp120 caused a two- to four-fold increase in the binding and uptake of isolated rod outer segments by RPE cells. These findings introduce a new cell target of HIV-1 replication in the eye and indicate that RPE cells function aberrantly when exposed to HIV-1 or its envelope glycoprotein.}, Author = {Canki, M. and Sparrow, J. R. and Chao, W. and Potash, M. J. and Volsky, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0889-2229}, Journal = {AIDS Res Hum Retroviruses}, Keywords = {Fetus;Human;Phagocytosis;Animals;HIV-1;Cells, Cultured;Hamsters;RNA, Viral;Comparative Study;Epithelial Cells;Recombinant Proteins;CHO Cells;15 Retrovirus mechanism;Cell Fusion;Antigens, CD4;11 Glia;Pigment Epithelium of Eye;Support, Non-U.S. Gov't;Adult;Support, U.S. Gov't, P.H.S.;Polymerase Chain Reaction;DNA, Viral;Virus Replication;Rod Outer Segments;HIV Envelope Protein gp120}, Medline = {20233485}, Month = {3}, Nlm_Id = {8709376}, Number = {5}, Organization = {Molecular Virology Laboratory, St. Luke's/Roosevelt Hospital Center, Columbia University, New York, New York 10019, USA.}, Pages = {453-63}, Pubmed = {10772531}, Title = {Human immunodeficiency virus type 1 can infect human retinal pigment epithelial cells in culture and alter the ability of the cells to phagocytose rod outer segment membranes}, Uuid = {49EDF80E-68CB-4EB5-B2EE-219AF6D10C70}, Volume = {16}, Year = {2000}, url = {papers/Canki_AIDSResHumRetroviruses2000.pdf}} @article{Cao:2003, Abstract = {As seizures in infants and children often originate from the neocortex, neocortical epilepsy models may be appropriate for studying epileptiform activity and seizure-induced injury in the developing nervous system. However, the characterization of epileptiform activity or seizure-induced injury in cultured developing cortical neurons has seldom been reported. Therefore, We attempted to establish a cultured developing cortical neuronal epilepsy model, and to study the subsequent effect on neurons. Cultures were exposed to Mg(2+)-free media for 3 h, and then returned to regular media. Using whole-cell patch-clamp intracellular recording techniques, we found that spontaneously recurrent epileptiform discharges for at least 72 h could be induced after transient Mg(2+)-free treatment. Neuron morphology following Mg(2+)-free treatment demonstrated no prominent alterations. At different time points (6, 24 and 72 h) after Mg(2+)-free treatment, neuronal viability, identified by trypan blue staining and LDH activity, and apoptosis, measured by flow cytometry, showed modest but non-significant (P>0.05) changes compared with the age-matched control group after various culture periods (6 and 17 days) in vitro. Mitochondrial metabolic activity, measured by MTT assay, significantly decreased by 15\%at 6 h after Mg(2+)-free treatment (P<0.05) in neurons cultured for 6 days, and at 24 h showed a 29\%decrease in neurons cultured for 17 days (P<0.05). In conclusion, brief Mg(2+)-free treatment constitutes a cultured developing cortical neuron 'seizure' model, and can induce transient mitochondrial dysfunction without cell loss.}, Author = {Cao, Hai-Yan Y. and Jiang, Yu-Wu W. and Liu, Zhen-Wei W. and Wu, Xi-Ru R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Electrophysiology;Animals;Cells, Cultured;Rats;Seizures;21 Epilepsy;Apoptosis;Mitochondria;Epilepsy;Patch-Clamp Techniques;Rats, Wistar;Embryo;Magnesium;Cerebral Cortex;Neurons;21 Neurophysiology;Membrane Potentials;24 Pubmed search results 2008;Models, Animal;Culture Media;Research Support, Non-U.S. Gov't}, Medline = {22580810}, Month = {4}, Nlm_Id = {8908639}, Number = {1}, Organization = {Division of Child Neurology, Department of Pediatrics, Peking University First Hospital, No. 1, Xi'anmen Dajie, Beijing 100034, PR China.}, Pages = {1-6}, Pii = {S0165380603000051}, Pubmed = {12694939}, Title = {Effect of recurrent epileptiform discharges induced by magnesium-free treatment on developing cortical neurons in vitro}, Uuid = {29E5F274-5100-45E7-BEF1-D3E8BDBC4F52}, Volume = {142}, Year = {2003}} @article{Capela:2006, Abstract = {LeX/SSEA1/CD15 is an extracellular matrix-associated carbohydrate expressed by ES cells and by adult neural and bone marrow stem cells. It is important for cell adhesion, compaction and FGF2 responses of early embryonic stem cells; however, its function at later stages is not clear. We now show that LeX is expressed by primary mouse neural progenitor cells, including neural stem cells, neuroblasts and glioblasts, but not by their more differentiated products. LeX distinguishes highly proliferative cells even in the primitive neuroepithelium, demonstrating heterogeneity in cell potential before radial glia arise. At later stages, LeX expressing progenitors are frequently radial in morphology. Surface LeX expression can be used to enrich neural stem and progenitor cells from different CNS regions throughout development by FACS. We found that LeX expression is particularly strong in neural regions with prolonged neurogenesis, e.g., the olfactory epithelium, hippocampus, basal forebrain and cerebellum. These regions also express high levels of the growth factors FGF8 and/or Wnt-1. We show here that LeX-containing molecules in the developing nervous system bind Wnt-1. Our findings suggest that LeX, which is present on the surface of principle neural progenitors and secreted into their extracellular niche, may bind and present growth factors important for their proliferation and self-renewal.}, Author = {Capela, and Temple,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {10 Development;03 Adult neurogenesis progenitor source;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0372762}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.}, Pii = {S0012-1606(05)00909-7}, Pubmed = {16458284}, Title = {LeX is expressed by principle progenitor cells in the embryonic nervous system, is secreted into their environment and binds Wnt-1}, Uuid = {92AF7DFD-C8DF-4738-9413-31C50398EF83}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2005.12.030}} @article{Capela:2002, Abstract = {Adult neural stem cells are rare, and little is known about their unique characteristics, leaving their in vivo identity enigmatic. We show that Lewis X (LeX), a carbohydrate expressed by embryonic pluripotent stem cells, is made by adult mouse subventricular zone (SVZ) stem cells and shed into their environment. Only 4\%of acutely isolated SVZ cells are LeX(+); this subpopulation, purified by FACS, contains the SVZ stem cells. Ependymal cells are LeX(-), and purified ependymal cells do not make neurospheres, resolving the controversial claim that these are stem cells. Thus, LeX expression by adult CNS stem cells aids their in vivo identification, allows their enrichment, and raises new questions about the role of this unusual carbohydrate in stem cell biology. 22260733 0896-6273 Journal Article}, Author = {Capela, A. and Temple, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {Neuron}, Keywords = {02 Adult neurogenesis migration;Antigens, CD15/*biosynthesis;Female;Central Nervous System/cytology/*metabolism;Ependyma/cytology/*metabolism;Animal;B-23;Support, U.S. Gov't, P.H.S.;Stem Cells/cytology/*metabolism;Support, Non-U.S. Gov't;Cells, Cultured;Mice;Brain/cytology/metabolism}, Number = {5}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA. alexandra.capela\@stemcellsinc.com}, Pages = {865-75}, Title = {LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal}, Uuid = {1E680164-BC67-44B2-99B8-49383C94419B}, Volume = {35}, Year = {2002}, url = {papers/Capela_Neuron2002.pdf}} @article{Cara:1997, Abstract = {During infection with different retroviruses, high levels of unintegrated extrachromosomal DNA accumulate in infected cells. While extrachromosomal linear DNA is the immediate precursor of the integrated provirus, the function, if any, of extrachromosomal circular DNA has been unclear. Several groups have attempted to address the possible function, activity, and importance of this unintegrated DNA during the life cycle of retroviruses and the course of retroviral-associated diseases. This review summarizes recent work in this field and tries to analyze some aspects of extrachromosomal forms of retroviral DNA and their possible application as a molecular biological tool.}, Author = {Cara, A. and Reitz, M. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0887-6924}, Journal = {Leukemia}, Keywords = {DNA, Circular;Virus Replication;Retroviridae;Transcription, Genetic;DNA, Viral;review, tutorial;15 Retrovirus mechanism;Extrachromosomal Inheritance;Humans;Animals;Retroviridae Infections;review;24 Pubmed search results 2008}, Medline = {97449094}, Month = {9}, Nlm_Id = {8704895}, Number = {9}, Organization = {Basic Research Laboratory, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.}, Pages = {1395-9}, Pubmed = {9305590}, Title = {New insight on the role of extrachromosomal retroviral DNA}, Uuid = {C15AE1AF-DF22-4017-B443-A4EC54C092B8}, Volume = {11}, Year = {1997}} @article{Carbonell:2005, Abstract = {Microglia rapidly become reactive in response to diverse stimuli and are thought to be prominent participants in the pathophysiology of both acute injury and chronic neurological diseases. However, mature microglial reactions to a focal lesion have not been characterized dynamically in adult vertebrate tissue. Here, we present a detailed analysis of long-distance perilesional microglial migration using time-lapse confocal microscopy in acutely isolated living slices from adult brain-injured mice. Extensive migration of perilesional microglia was apparent by 24 h after injury and peaked at 3 d. Average instantaneous migration speeds of approximately 5 microm/min and peak speeds >10 microm/min were observed. Collective, directed migration toward the lesion edge was not observed as might be expected in the presence of chemoattractive gradients. Rather, migration was autonomous and could be modeled as a random walk. Pharmacological blockade of the cysteine-cysteine chemokine receptor 5 reduced migration velocity and the number of perilesional migratory microglia without affecting directional persistence, suggesting a novel role for chemokines in modulation of discrete migratory parameters. Finally, activated microglia in the denervated hippocampal stratum oriens did not migrate extensively, whereas human immunodeficiency virus-1 tat-activated microglia migrated nearly twice as fast as those at the stab lesion, indicating a nonuniform microglial response to different stimuli. Understanding the characteristics and specific molecular mechanisms underlying microglial migration after neural injury could reveal novel targets for therapeutic strategies for modulating neuroinflammation in human diseases.}, Author = {Carbonell, W. Shawn and Murase, Shin-Ichi and Horwitz, Alan F. and Mandell, James W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Alpha;11 Glia}, Month = {7}, Nlm_Id = {8102140}, Number = {30}, Organization = {Medical Scientist Training Program, Division of Neuropathology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.}, Pages = {7040-7}, Pii = {25/30/7040}, Pubmed = {16049180}, Title = {Migration of perilesional microglia after focal brain injury and modulation by CC chemokine receptor 5: an in situ time-lapse confocal imaging study}, Uuid = {66AD9FD0-5414-4591-8028-BD02718578CE}, Volume = {25}, Year = {2005}, url = {papers/Carbonell_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5171-04.2005}} @article{Cardona:2006, Abstract = {Microglia, the resident inflammatory cells of the CNS, are the only CNS cells that express the fractalkine receptor (CX3CR1). Using three different in vivo models, we show that CX3CR1 deficiency dysregulates microglial responses, resulting in neurotoxicity. Following peripheral lipopolysaccharide injections, Cx3cr1-/- mice showed cell-autonomous microglial neurotoxicity. In a toxic model of Parkinson disease and a transgenic model of amyotrophic lateral sclerosis, Cx3cr1-/- mice showed more extensive neuronal cell loss than Cx3cr1+ littermate controls. Augmenting CX3CR1 signaling may protect against microglial neurotoxicity, whereas CNS penetration by pharmaceutical CX3CR1 antagonists could increase neuronal vulnerability.}, Author = {Cardona, Astrid E. and Pioro, Erik P. and Sasse, Margaret E. and Kostenko, Volodymyr and Cardona, Sandra M. and Dijkstra, Ineke M. and Huang, Deren and Kidd, Grahame and Dombrowski, Stephen and Dutta, RanJan and Lee, Jar-Chi C. and Cook, Donald N. and Jung, Steffen and Lira, Sergio A. and Littman, Dan R. and Ransohoff, Richard M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Neurotoxicity Syndromes;research support, n.i.h., extramural ;Animals;Cells, Cultured;Microglia;Lipopolysaccharides;Mice, Transgenic;Parkinson Disease;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;comparative study ;Disease Models, Animal;research support, non-u.s. gov't ;Analysis of Variance;Receptors, Chemokine;Neurons;Calcium-Binding Proteins;Flow Cytometry;Mice;Motor Neuron Disease;24 Pubmed search results 2008;Central Nervous System;Immunohistochemistry;Cell Death;Nerve Tissue Proteins;Cytokines}, Month = {7}, Nlm_Id = {9809671}, Number = {7}, Organization = {Neuroinflammation Research Center and Department of Neurosciences, Lerner Research Institute, Cleveland, Ohio 44195, USA.}, Pages = {917-24}, Pii = {nn1715}, Pubmed = {16732273}, Title = {Control of microglial neurotoxicity by the fractalkine receptor}, Uuid = {46AFD8D0-8775-4F51-B487-D873A909F8EE}, Volume = {9}, Year = {2006}, url = {papers/Cardona_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1715}} @article{Caric:1997, Abstract = {The cerebral cortex forms by the orderly migration and subsequent differentiation of neuronal precursors generated in the proliferative ventricular zone. We studied the role of the transcription factor Pax-6, which is expressed in the ventricular zone, in cortical development. Embryos homozygous for a mutation of Pax-6 (Small eye; Sey) had abnormalities suggesting defective migration of late-born cortical precursors. When late-born Sey/Sey precursors were transplanted into wild-type embryonic rat cortex, they showed similar integrative, migrational and differentiative abilities to those of transplanted wild-type mouse precursors. These results suggest that postmitotic cortical cells do not need Pax-6 to acquire the capacity to migrate and differentiate, but that Pax-6 generates a cortical environment that permits later-born precursors to express their full developmental potential. 0950-1991 Journal Article}, Author = {Caric, D. and Gooday, D. and Hill, R. E. and McConnell, S. K. and Price, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Development}, Keywords = {Leukocyte L1 Antigen Complex;Pregnancy;DNA-Binding Proteins/genetics/*physiology;Animals;10 Development;Tubulin/analysis;Rats;Cell Movement/*physiology;Eye Abnormalities;Membrane Glycoproteins/analysis;Female;Transcription Factors/genetics/*physiology;F pdf;Point Mutation/physiology;Mice, Neurologic Mutants;RNA, Messenger/analysis;Support, Non-U.S. Gov't;Cerebral Cortex/chemistry/*cytology/*embryology;Cell Transplantation;Support, U.S. Gov't, P.H.S.;Telencephalon/chemistry/cytology/embryology;Mice;Cell Adhesion Molecules, Neuronal/analysis;*Homeodomain Proteins;Neuroglia/cytology}, Number = {24}, Organization = {MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.}, Pages = {5087-96}, Pubmed = {9362466}, Title = {Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6}, Uuid = {0E7E510C-0881-4F06-98E7-42B16FCA3AC1}, Volume = {124}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9362466}} @article{Caric:2001, Abstract = {Epidermal growth factor receptors (EGFRs) have been implicated in the control of migration in the telencephalon, but the mechanism underlying their contribution is unclear. We show that expression of a threshold level of EGFRs confers chemotactic competence in stem cells, neurons and astrocytes in cortical explants. This level of receptor expression is normally achieved by a subpopulation of cells during mid-embryonic development. Cells that express high levels of EGFR are located in migration pathways, including the tangential pathway to the olfactory bulb via the rostral migratory stream (RMS), the lateral cortical stream (LCS) leading to ventrolateral cortex and the radial pathway from proliferative zones to cortical plate. The targets of these pathways express the ligands HB-EGF and/or TGFalpha. To test the idea that EGFRs mediate chemotactic migration these pathways, we increased the size of the population of cells expressing threshold levels of EGFRs in vivo by viral transduction. Our results suggest that EGFRs mediate migration radially to the cortical plate and ventrolaterally in the LCS, but not tangentially in the RMS. Within the bulb, however, EGFRs also mediate radial migration. Our findings suggest that developmental changes in EGFR expression, together with changes in ligand expression regulate the migration of specific populations of cells in the telencephalon by a chemoattractive mechanism.}, Author = {Caric, D. and Raphael, H. and Viti, J. and Feathers, A. and Wancio, D. and Lillien, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Development}, Keywords = {Chemotaxis/*physiology;Rats, Sprague-Dawley;Transplants;Female;Epidermal Growth Factor/genetics/immunology/metabolism;Rats;Transforming Growth Factor alpha/metabolism;Embryonic Induction;Animal;Receptor, Epidermal Growth Factor/genetics/*metabolism;Pregnancy;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Telencephalon/*embryology/metabolism/transplantation;C abstr}, Number = {21}, Organization = {Department of Neurobiology and Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, W1454 Biomedical Science Tower, Pittsburgh, PA 15261, USA.}, Pages = {4203-16.}, Title = {EGFRs mediate chemotactic migration in the developing telencephalon}, Uuid = {3C24400D-2EF2-4FDB-B5A0-81385F4F4314}, Volume = {128}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11684657%20http://dev.biologists.org/cgi/content/full/128/21/4203%20http://dev.biologists.org/cgi/content/abstract/128/21/4203}} @article{Carlen:2002, Abstract = {Over the past decade, it has become clear that neural stem cells in the adult mammalian brain continuously generate new neurons, predominantly in the hippocampus and olfactory bulb. However, the central issue of whether these new neurons participate in functional synaptic circuitry has yet to be resolved. Here, we use virus-based transsynaptic neuronal tracing and c-Fos mapping of odor-induced neuronal activity to demonstrate that neurons generated in the adult functionally integrate into the synaptic circuitry of the brain.}, Author = {Carlen, M. and Cassidy, R. M. and Brismar, H. and Smith, G. A. and Enquist, L. W. and Frisen, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {Curr Biol}, Keywords = {01 Adult neurogenesis general;A both}, Number = {7}, Organization = {Department of Cell and Molecular Biology, Medical Nobel Institute, Stockholm, Sweden}, Pages = {606-8.}, Title = {Functional integration of adult-born neurons}, Uuid = {258B37FE-8387-4DD0-AF08-FD776A092463}, Volume = {12}, Year = {2002}, url = {papers/Carlen_CurrBiol2002}} @article{Carleton:2002, Abstract = {Olfaction was long considered to belong more to the realm of art than to that of science. As a result, how the brain perceives, discriminates, and recognizes odorant molecules is still a mystery. Recent progress has nonetheless been made at early stages of the olfactory pathway when olfactory studies entered into the molecular era to elucidate the first contact of an odor molecule with a receptor. Our group focuses on the analysis of odor information in the olfactory bulb, the first processing relay in the mammalian brain. Using this model, we are attempting to decipher the code for odorant information. Furthermore, the olfactory bulb also provides an attractive model to investigate neuronal proliferation, differentiation, migration, and neuronal death, processes involving an interplay between genetic and epigenetic influences. Finally, our goal is to explore the possible consequences of the olfactory bulb plasticity, in olfactory performance. For these purposes, we aim to combine morphological, electrophysiological and behavioral approaches to investigate: (1) how the olfactory bulb processes odor molecule information, (2) how neural precursors differentiate into olfactory bulb interneurons, (3) how these newly-generated neurons integrate into an operational neural network, (4) what role they play in the adult olfactory bulb, and (5) how are basic olfactory functions maintained in such a sensory system subjected to continuous renewal of a large percentage of its neuronal population. These questions should provide new fuel for the molecular and cellular bases of sensory perception and shed light onto cellular bases of learning and memory.}, Author = {Carleton, A. and Rochefort, C. and Morante-Oria, J. and Desmaisons, D. and Vincent, J. D. and Gheusi, G. and Lledo, P. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:43 -0400}, Journal = {J Physiol Paris}, Keywords = {B both;02 Adult neurogenesis migration}, Number = {1-2}, Organization = {C.N.R.S., UPR 2197, Unite "Developpement, Evolution, Plasticite du Systeme Nerveux", Avenue de la Terrasse, 91198 Cedex, Gif-sur-Yvette, France}, Pages = {115-22.}, Title = {Making scents of olfactory neurogenesis}, Uuid = {F0986BA5-FF8E-4E45-8F60-22033BB48238}, Volume = {96}, Year = {2002}, url = {papers/Carleton_JPhysiolParis2002.pdf}} @article{Carleton:2003, Abstract = {New neurons are continually recruited throughout adulthood in certain regions of the adult mammalian brain. How these cells mature and integrate into preexisting functional circuits remains unknown. Here we describe the physiological properties of newborn olfactory bulb interneurons at five different stages of their maturation in adult mice. Patch-clamp recordings were obtained from tangentially and radially migrating young neurons and from neurons in three subsequent maturation stages. Tangentially migrating neurons expressed extrasynaptic GABA(A) receptors and then AMPA receptors, before NMDA receptors appeared in radially migrating neurons. Spontaneous synaptic activity emerged soon after migration was complete, and spiking activity was the last characteristic to be acquired. This delayed excitability is unique to cells born in the adult and may protect circuits from uncontrolled neurotransmitter release and neural network disruption. Our results show that newly born cells recruited into the olfactory bulb become neurons, and a unique sequence of events leads to their functional integration. 1097-6256 Journal Article}, Author = {Carleton, A. and Petreanu, L. T. and Lansford, R. and Alvarez-Buylla, A. and Lledo, P. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Synaptic Transmission/drug effects/physiology;Cell Differentiation;Neurons/*cytology/drug effects/*physiology;Animals;In Vitro;Synaptic Transmission;Cell Movement;Mice, Inbred C57BL;Male;Olfactory Bulb;Animals, Newborn;Support, Non-U.S. Gov't;Cell Movement/drug effects/physiology;Research Support, U.S. Gov't, P.H.S.;Neurons;Olfactory Bulb/*cytology/drug effects/*growth &development;Support, U.S. Gov't, P.H.S.;Mice;Cell Differentiation/physiology;A pdf;Research Support, Non-U.S. Gov't}, Medline = {22600675}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Pasteur Institute, Laboratory of Perception and Memory, CNRS UMR 2182, 25 Rue du Dr Roux, 75015 Paris, France.}, Pages = {507-18}, Pii = {nn1048}, Pubmed = {12704391}, Title = {Becoming a new neuron in the adult olfactory bulb}, Uuid = {3C8CAB4B-CDEF-11D9-B244-000D9346EC2A}, Volume = {6}, Year = {2003}, url = {papers/Carleton_NatNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1048}} @article{Carmeliet:2005, Abstract = {The growth of blood vessels (a process known as angiogenesis) is essential for organ growth and repair. An imbalance in this process contributes to numerous malignant, inflammatory, ischaemic, infectious and immune disorders. Recently, the first anti-angiogenic agents have been approved for the treatment of cancer and blindness. Angiogenesis research will probably change the face of medicine in the next decades, with more than 500 million people worldwide predicted to benefit from pro- or anti-angiogenesis treatments.}, Author = {Carmeliet, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Drug Resistance, Neoplasm;10 Development;Research Support, Non-U.S. Gov't;Bone Marrow Cells;14 Immune;Neovascularization, Physiologic;Neoplasms;Blood Vessels;Animals;Humans;24 Pubmed search results 2008;review;Neovascularization, Pathologic}, Month = {12}, Nlm_Id = {0410462}, Number = {7070}, Organization = {Center of Transgene Technology and Gene Therapy, University of Leuven, Flanders Interuniversity Institute for Biotechnology (VIB), B-3000 Leuven, Belgium. peter.carmeliet\@med.kuleuven.be}, Pages = {932-6}, Pii = {nature04478}, Pubmed = {16355210}, Title = {Angiogenesis in life, disease and medicine}, Uuid = {94D2D284-F69B-43E0-B269-EE327AF32ED3}, Volume = {438}, Year = {2005}, url = {papers/Carmeliet_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04478}} @article{Carmichael:2002, Abstract = {The ability of the adult brain to form new connections in areas denervated by a lesion (axonal sprouting) is more widespread than previously thought, but mechanisms remain unknown. We have previously demonstrated an unexpected, robust axonal sprouting of contralateral corticostriatal neurons into the denervated striatum after ischemic cortical lesions. We now take advantage of marked differences in the degree of axonal sprouting from contralateral homotypic cortex after two types of cortical lesions to define the role of neuronal activity in this response. Thermal-ischemic lesions (TCL) of sensorimotor cortex, which induce axonal sprouting, produced two sequential patterns of low-frequency, synchronized neuronal activity that are not seen after similarly sized aspiration lesions, which do not induce axonal sprouting. An early rhythm of synchronous neuronal activity occurred in perilesion cortex on day 1 after lesion, with a frequency range of 0.2-2 Hz. A later pattern of activity occurred on days 2 and 3 after lesion, with a frequency range of 0.1-0.4 Hz. This second rhythm synchronized neuronal activity across widespread areas, including the cortical areas that contain the cell bodies of the sprouting axons. TTX was used to block this patterned neuronal activity and determine whether axonal sprouting was prevented. Chronic TTX infusion into the lesion site blocked the synchronous neuronal activity after TCL as well as axonal sprouting. Thus, both after different types of lesions and in the blockade experiments axonal sprouting was strongly correlated with synchronous neuronal activity, suggesting a role for this activity in anatomical reorganization after brain lesion in the adult.}, Author = {Carmichael, S. Thomas and Chesselet, Marie-Fran\c{c}oise F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Corpus Striatum;Rats;Neuronal Plasticity;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Cell Communication;Rats, Sprague-Dawley;Periodicity;Axons;Tetrodotoxin;Male;Nerve Regeneration;research support, non-u.s. gov't ;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;Neurons;Somatosensory Cortex;21 Cortical oscillations;24 Pubmed search results 2008;Cerebral Decortication;Electroencephalography;Electrodes, Implanted;Electrocoagulation}, Medline = {22117911}, Month = {7}, Nlm_Id = {8102140}, Number = {14}, Organization = {Department of Neurology, University of California Los Angeles, Los Angeles, California 90095, USA. scarmichael\@mednet.ucla.edu}, Pages = {6062-70}, Pii = {22/14/6062}, Pubmed = {12122067}, Title = {Synchronous neuronal activity is a signal for axonal sprouting after cortical lesions in the adult}, Uuid = {49D83BE0-4483-4AAC-A898-6437A2B8C3D5}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/20026605}} @article{Carmona:2006, Abstract = {Patterned intrinsic network activity plays a central role in shaping immature neuronal networks into functional circuits. However, the long-lasting signals that regulate spontaneous activity of developing circuits have not been identified. Here we study the net impact of TrkB signaling on early network activity of identified neuronal populations by analyzing postnatal hippocampi from trkB null mice. Ca2+ imaging showed that pyramidal neurons of trkB-/- mice displayed a decrease in intrinsic synchronous activity in neonatal animals but an increase in juveniles. Strikingly, alterations in network activity in trkB-/- hippocampus were associated with an aberrant induction of the transcription factor Fos. In contrast to pyramidal neurons, spontaneous [Ca2+]i oscillations in trkB-/- interneurons were consistently impaired throughout postnatal development. Moreover, the number of GABAergic synapses and the expression levels of GAD65 and KCC2 were decreased in mutant hippocampi, indicating that pre- and post-synaptic GABAergic components were impaired in trkB-/- mice. Finally, the partial blockade of GABA(A) receptor in postnatal slices revealed that mutant hippocampi displayed an increased susceptibility to network hyperexcitability. These results indicate that the lack of TrkB signaling during development impairs GABAergic neurotransmission, thereby leading to an age-dependent decrease followed by an increase in the intrinsic excitability of neuronal circuits. Furthermore, the present study indicates that long-lasting TrkB signaling may contribute to the construction of CNS circuits by modulating patterns of spontaneous [Ca2+]i oscillations.}, Author = {Carmona, Maria A. and Pozas, Esther and Mart{\'\i}nez, Albert and Espinosa-Parrilla, Juan F. and Soriano, Eduardo and Aguado, Fernando}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {gamma-Aminobutyric Acid;10 Development;Signal Transduction;Calcium Signaling;Animals;Aging;Neuronal Plasticity;Synaptic Transmission;Hippocampus;Mice, Inbred C57BL;Biological Clocks;research support, non-u.s. gov't;Animals, Newborn;Nerve Net;Mice, Knockout;Receptor, trkB;10 genetics malformation;Mice;Interneurons;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {9110718}, Number = {1}, Organization = {Department of Cell Biology and IRBB-Barcelona Science Park, University of Barcelona, Barcelona E-08028, Spain.}, Pages = {47-63}, Pii = {bhi083}, Pubmed = {15829735}, Title = {Age-dependent spontaneous hyperexcitability and impairment of GABAergic function in the hippocampus of mice lacking trkB}, Uuid = {CD196995-D831-420D-A249-2065EDC07B70}, Volume = {16}, Year = {2006}, url = {papers/Carmona_CerebCortex2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhi083}} @article{Carneiro:2006, Abstract = {The entry of enveloped animal viruses into their host cells always depends on membrane fusion triggered by conformational changes in viral envelope glycoproteins. Vesicular stomatitis virus (VSV) infection is mediated by virus spike glycoprotein G, which induces membrane fusion between the viral envelope and the endosomal membrane at the acidic environment of this compartment. In this work, we evaluated VSV interactions with membranes of different phospholipid compositions, at neutral and acidic pH, using atomic force microscopy (AFM) operating in the force spectroscopy mode, isothermal calorimetry (ITC) and molecular dynamics simulation. We found that the binding forces differed dramatically depending on the membrane phospholipid composition, revealing a high specificity of G protein binding to membranes containing phosphatidylserine (PS). In a previous work, we showed that the sequence corresponding amino acid 164 of VSV G protein was as efficient as the virus in catalyzing membrane fusion at pH 6.0. Here, we used this sequence to explore VSV-PS interaction using ITC. We found that peptide binding to membranes was exothermic, suggesting the participation of electrostatic interactions. Peptide-membrane interaction at pH 7.5 was shown to be specific to PS and dependent on the presence of His residues in the fusion peptide. The application of the simplified continuum Gouy-Chapman theory to our system predicted a pH of 5.0 at membrane surface, suggesting that the His residues should be protonated when located close to the membrane. Molecular dynamics simulations suggested that the peptide interacts with the lipid bilayer through its N-terminal residues, especially Val(145) and His(148).}, Author = {Carneiro, Fabiana A. and Lapido-Loureiro, Pedro A. and Cordo, Sandra M. and Stauffer, Fausto and Weissm{\"u}ller, Gilberto and Bianconi, M. Lucia and Juliano, Maria A. and Juliano, Luiz and Bisch, Paulo M. and Poian, Andrea T. Da}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0175-7571}, Journal = {Eur Biophys J}, Keywords = {15 PS VSVG receptor;15 Retrovirus mechanism;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8409413}, Number = {2}, Organization = {Instituto de Bioqu\`{i}mica M{\'e}dica, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-590, Brazil.}, Pages = {145-54}, Pubmed = {16184389}, Title = {Probing the interaction between vesicular stomatitis virus and phosphatidylserine}, Uuid = {108FA85E-F7CC-43F8-A9DD-EA7CC4218326}, Volume = {35}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00249-005-0012-z}} @article{Carneiro:2002, Abstract = {Vesicular stomatitis virus (VSV) infection depends on the fusion of viral and cellular membranes, which is mediated by virus spike glycoprotein G at the acidic environment of the endosomal compartment. VSV G protein does not contain a hydrophobic amino acid sequence similar to the fusion peptides found among other viral glycoproteins, suggesting that membrane recognition occurs through an alternative mechanism. Here we studied the interaction between VSV G protein and liposomes of different phospholipid composition by force spectroscopy, isothermal titration calorimetry (ITC), and fluorescence spectroscopy. Force spectroscopy experiments revealed the requirement for negatively charged phospholipids for VSV binding to membranes, suggesting that this interaction is electrostatic in nature. In addition, ITC experiments showed that VSV binding to liposomes is an enthalpically driven process. Fluorescence data also showed the lack of VSV interaction with the vesicles as well as inhibition of VSV-induced membrane fusion at high ionic strength. Intrinsic fluorescence measurements showed that the extent of G protein conformational changes depends on the presence of phosphatidylserine (PS) on the target membrane. Although the increase in PS content did not change the binding profile, the rate of the fusion reaction was remarkably increased when the PS content was increased from 25 to 75\%. On the basis of these data, we suggest that G protein binding to the target membrane essentially depends on electrostatic interactions, probably between positive charges on the protein surface and negatively charged phospholipids in the cellular membrane. In addition, the fusion is exothermic, indicating no entropic constraints to this process.}, Author = {Carneiro, Fabiana A. and Bianconi, M. Lucia and Weissm{\"u}ller, Gilberto and Stauffer, Fausto and Da Poian, Andrea T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Electrostatics;Animals;Vesicular stomatitis-Indiana virus;Spectrometry, Fluorescence;Microscopy, Atomic Force;Thermodynamics;Cell Membrane;Liposomes;15 Retrovirus mechanism;Calorimetry;Viral Envelope Proteins;Cell Line;Membrane Glycoproteins;Membrane Fusion;Phospholipids;Cricetinae;24 Pubmed search results 2008;15 PS VSVG receptor;Research Support, Non-U.S. Gov't}, Medline = {21904718}, Month = {4}, Nlm_Id = {0113724}, Number = {8}, Organization = {Departamento de Bioqu{\'\i}mica M{\'e}dica, Instituto de Ci\^{e}ncias Biom{\'e}dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brazil.}, Pages = {3756-64}, Pubmed = {11907215}, Title = {Membrane recognition by vesicular stomatitis virus involves enthalpy-driven protein-lipid interactions}, Uuid = {9EC4BC91-5941-4C88-B3D1-91C530C801F5}, Volume = {76}, Year = {2002}} @article{Carp:2002, Abstract = {A series of inbred strains of mice have been developed that are either prone (SAMP) or resistant (SAMR) to accelerated senescence. All of these strains originated from an inadvertent cross or crosses between the AKR/J mouse strain and an unknown strain(s). The characteristics of the nine senescence-prone lines differ, with all strains showing generalized aspects of accelerated aging but with each line having a specific aging-related change that is emphasized, e.g. learning and memory deficits, osteoporosis and senile amyloidosis. The senescence-resistant strains have normal patterns of aging and do not show the specific aging-related changes seen in SAMP strains. The fact that AKR mice have high levels of endogenous, ecotropic murine leukemia virus (MuLV) prompted an examination of the expression levels of MuLV in SAM strains. Analysis of brain, spleen and thymus samples revealed that seven of nine SAMP strains had high levels of MuLV and contained the Emv11 provirus (previously termed Akv1) that encodes the predominant MuLV found in AKR mice. In contrast, none of the SAMR strains had Emv11 or significant amounts of virus. The current findings represent an initial step in determining the role of MuLV in the accelerated senescence seen in SAMP strains.}, Author = {Carp, R. I. and Meeker, H. C. and Chung, R. and Kozak, C. A. and Hosokawa, M. and Fujisawa, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0047-6374}, Journal = {Mech Ageing Dev}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Aging;Brain;Female;15 Retrovirus mechanism;Crosses, Genetic;Male;Proviruses;Cell Line;Animals, Newborn;Leukemia Virus, Murine;Thymus Gland;Mice;24 Pubmed search results 2008;15 ERVs retroelements;Spleen;Mice, Inbred AKR}, Medline = {21839529}, Month = {3}, Nlm_Id = {0347227}, Number = {6}, Organization = {New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314, USA. richard.carp\@omr.state.ny.us}, Pages = {575-84}, Pii = {S0047637401003773}, Pubmed = {11850021}, Title = {Murine leukemia virus in organs of senescence-prone and -resistant mouse strains}, Uuid = {833A211C-4326-11DB-A5D2-000D9346EC2A}, Volume = {123}, Year = {2002}} @article{Carr:1992, Abstract = {Young adult rats were unilaterally bulbectomized and tritiated thymidine ([3H]TdR) was injected at variable times following surgery to determine the effect of bulbectomy on the rates of cell proliferation and cell death in the olfactory epithelium. Removal of the olfactory bulb elicits a two- to fourfold increase in the proliferation rate of ipsilateral olfactory epithelial cells 7-50 days following surgery. On the contralateral side, there was a temporary twofold increase in the proliferation rate during the second week after surgery, but this returned to control values at 3 weeks. This temporary increase was in parallel with the response on the ipsilateral side so that the ratio between operated and unoperated sides remained at two. Cell death in olfactory epithelium is also up-regulated following bulbectomy. Death of cells can occur as early as 1 day following incorporation of [3H]TdR, i.e., well before the sensory neurons become mature. This means there is an over-production of sensory cells, and they die at all stages of their life cycle. The number of cells dying is greater after bulbectomy, indicating that the overproduction of olfactory cells is more pronounced after surgery.}, Author = {Carr, V. M. and Farbman, A. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Exp Neurol}, Keywords = {Support, U.S. Gov't, P.H.S.;Tritium;Neurons, Afferent/physiology;Nerve Degeneration;Rats;Autoradiography;Thymidine/metabolism;Neurons/cytology/*physiology;Animal;Cell Death;DNA Replication;I abstr;Olfactory Bulb/*physiology;Olfactory Mucosa/cytology/innervation/*physiology;13 Olfactory bulb anatomy;Epithelium/cytology/physiology;*Nerve Regeneration}, Number = {1}, Organization = {Department of Neurobiology and Physiology, Northwestern University, Evanston, Illinois 60208-3520.}, Pages = {55-9.}, Title = {Ablation of the olfactory bulb up-regulates the rate of neurogenesis and induces precocious cell death in olfactory epithelium}, Uuid = {E149A3D1-A46D-4253-9399-F28482F8D432}, Volume = {115}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1728573}} @article{Carroll:2008, Abstract = {Biologists have long sought to understand which genes and what kinds of changes in their sequences are responsible for the evolution of morphological diversity. Here, I outline eight principles derived from molecular and evolutionary developmental biology and review recent studies of species divergence that have led to a genetic theory of morphological evolution, which states that (1) form evolves largely by altering the expression of functionally conserved proteins, and (2) such changes largely occur through mutations in the cis-regulatory sequences of pleiotropic developmental regulatory loci and of the target genes within the vast networks they control.}, Author = {Carroll, Sean B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008;research support, non-u.s. gov't;Evolution, Molecular;Evolution;Animals;Humans;Proteins;Developmental Biology;Gene Regulatory Networks}, Month = {7}, Nlm_Id = {0413066}, Number = {1}, Organization = {Howard Hughes Medical Institute, Laboratory of Molecular Biology, University of Wisconsin-Madison, Madison, WI 53706, USA. sbcarrol\@wisc.edu}, Pages = {25-36}, Pii = {S0092-8674(08)00817-9}, Pubmed = {18614008}, Title = {Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution}, Uuid = {15AA6C3C-CCF7-443F-88B2-8D1FF0DC4A23}, Volume = {134}, Year = {2008}, url = {papers/Carroll_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.06.030}} @article{Carson:2006, Abstract = {Central nervous system (CNS) immune privilege is an experimentally defined phenomenon. Tissues that are rapidly rejected by the immune system when grafted in sites, such as the skin, show prolonged survival when grafted into the CNS. Initially, CNS immune privilege was construed as CNS isolation from the immune system by the blood-brain barrier (BBB), the lack of draining lymphatics, and the apparent immunoincompetence of microglia, the resident CNS macrophage. CNS autoimmunity and neurodegeneration were presumed automatic consequences of immune cell encounter with CNS antigens. Recent data have dramatically altered this viewpoint by revealing that the CNS is neither isolated nor passive in its interactions with the immune system. Peripheral immune cells can cross the intact BBB, CNS neurons and glia actively regulate macrophage and lymphocyte responses, and microglia are immunocompetent but differ from other macrophage/dendritic cells in their ability to direct neuroprotective lymphocyte responses. This newer view of CNS immune privilege is opening the door for therapies designed to harness autoreactive lymphocyte responses and also implies (i) that CNS autoimmune diseases (i.e. multiple sclerosis) may result as much from neuronal and/or glial dysfunction as from immune system dysfunctions and (ii) that the severe neuronal and glial dysfunction associated with neurodegenerative disorders (i.e. Alzheimer's disease) likely alters CNS-specific regulation of lymphocyte responses affecting the utility of immune-based therapies (i.e. vaccines).}, Author = {Carson, Monica J. and Doose, Jonathan M. and Melchior, Benoit and Schmid, Christoph D. and Ploix, Corinne C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0105-2896}, Journal = {Immunol Rev}, Keywords = {14 Immune;11 Glia;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {7702118}, Organization = {Division of Biomedical Sciences, University of California, Riverside, Riverside, CA, USA.}, Pages = {48-65}, Pii = {IMR441}, Pubmed = {16972896}, Title = {CNS immune privilege: hiding in plain sight}, Uuid = {93DE4D67-E9D3-47D5-818D-DFB3FACC695C}, Volume = {213}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1600-065X.2006.00441.x}} @article{Carson:2005, Abstract = {Olfactory receptor neurons (ORNs) undergo caspase-mediated retrograde apoptosis after target removal (bulbectomy), in which axonal caspase-9 and caspase-3 activation leads to terminal apoptosis in ORN soma of the olfactory epithelium. Here, we show that caspase-8 can act as an initiator of ORN apoptosis after bulbectomy and also after synaptic instability is induced by NMDA-mediated excitotoxic death of ORN target neurons in the olfactory bulb. Caspase-8 and caspase-3 are sequentially activated within ORN presynaptic terminals, and caspase-8 complexes with dynactin p150Glued, (a retrograde motor protein) and is transported retrogradely, preceding axonal caspase-3 activation and apoptosis of ORN cell bodies. Focal in vivo inhibition of initiator caspase activation or microtubule-dependent transport (with Taxol) at the lesioned axon terminus results in a significant reduction in retrograde axonal caspase-8 and caspase-3 activation and inhibition of retrograde ORN death. Caspase-8 activation and retrograde transport after NMDA lesion is similarly reduced in mice null for p75, the low-affinity nerve growth factor receptor. The retrograde apoptosis of ORNs thus involves a novel mechanism that used p75 in the local activation of caspase-8. Once caspase-8 is maximally activated in the presynaptic terminal, it is transported retrogradely by the motor complex dynactin/dynein, a process that can be inhibited focally to inhibit ORN apoptosis after acute axonal lesion. These data have revealed a novel mechanism of retrograde apoptosis, in which caspase-8 complexes directly with axonal dynactin p150Glued to reveal a differential vulnerability of subpopulations of ORNs to undergo apoptosis after axonal damage and the loss of olfactory bulb target neurons.}, Author = {Carson, Christine and Saleh, Maya and Fung, France W. and Nicholson, Donald W. and Roskams, A. Jane}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {8102140}, Number = {26}, Organization = {Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.}, Pages = {6092-104}, Pii = {25/26/6092}, Pubmed = {15987939}, Title = {Axonal dynactin p150Glued transports caspase-8 to drive retrograde olfactory receptor neuron apoptosis}, Uuid = {C1422DF8-8C94-4B6C-9A45-B45A7503AC05}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0707-05.2005}} @article{Carter:2007, Abstract = {Recurrent excitation is believed to underlie persistent neural activity observed in the prefrontal cortex and elsewhere during working memory. However, other positive and negative feedback mechanisms, operating on disparate timescales, may also play significant roles in determining the behavior of a working memory circuit. In this study, we examined dynamical interactions of multiple feedback mechanisms in a biophysically based neural model of spatial working memory. In such continuous attractor networks, a self-sustained activity pattern tends to drift randomly, resulting in a decreased accuracy of memory over time. Moreover, attractor states become unstable when spike-frequency adaptation reduces the excitability of persistently firing pyramidal neurons. Here, we show that a slow activity-dependent local disinhibition, namely cannabinoid-dependent depolarization-induced suppression of inhibition (DSI), can counteract these destabilizing effects, rendering working memory function more robust. In addition, the slow DSI effect gives rise to trial-to-trial correlations of memory-guided behavioral responses. On the other hand, computer simulations revealed that a global cannabinoid agonist (mimicking the effect of drug intake) yields the opposite effect. Thus, this work suggests a circuit scenario according to which endogenous DSI is beneficial for, whereas an exogenous drug such as marijuana is detrimental to, working memory and possibly other prefrontal functions.}, Author = {Carter, Eugene and Wang, Xiao-Jing J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Data Interpretation, Statistical;Memory, Short-Term;Neural Networks (Computer);Space Perception;Models, Neurological;Feedback;Prefrontal Cortex;Pyramidal Cells;Algorithms;Cues;research support, n.i.h., extramural;Cannabinoids;Calcium Signaling;Calcium Channels;Computer Simulation;Membrane Potentials;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {9110718}, Organization = {Department of Biology, Brandeis University, Waltham, MA 02454-9110, USA.}, Pages = {i16-26}, Pii = {17/suppl_1/i16}, Pubmed = {17725998}, Title = {Cannabinoid-mediated disinhibition and working memory: dynamical interplay of multiple feedback mechanisms in a continuous attractor model of prefrontal cortex}, Uuid = {AF284BE5-7F4D-400C-B50A-DFEFDBCCB75A}, Volume = {17 Suppl 1}, Year = {2007}, url = {papers/Carter_CerebCortex2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhm103}} @article{Carter:2002, Abstract = {Many small synaptic inputs or one large input are needed to influence principal cell firing, whereas individual quanta exert little influence. However, the role of a quantum may be greater for small interneurons with high input resistances. Using dynamic clamp recordings, we found that individual quanta strongly influence rat cerebellar stellate cell firing. When the frequency of synaptic inputs was low, the timing of recent spikes regulated the influence of excitatory quanta. In contrast, when input frequency was high, spike timing was less important than interactions with other inputs. Inhibitory quanta rapidly terminated firing, whereas small numbers of coincident excitatory quanta reliably and rapidly triggered firing. Our results suggest that stellate cells achieve temporal precision through coincidence detection and disynaptic inhibition, despite their high resistances and long membrane time constants. Thus, we propose that small interneurons can process synaptic inputs in a fundamentally different way from principal cells.}, Author = {Carter, Adam G. and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Electric Stimulation;Presynaptic Terminals;Animals;Rats;Neural Pathways;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Synaptic Vesicles;Rats, Sprague-Dawley;Reaction Time;Cerebellar Cortex;Animals, Newborn;Action Potentials;Potassium Channels;21 Neurophysiology;GABA Antagonists;Interneurons;24 Pubmed search results 2008;Neural Inhibition;Excitatory Postsynaptic Potentials}, Month = {12}, Nlm_Id = {9809671}, Number = {12}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.}, Pages = {1309-18}, Pii = {nn970}, Pubmed = {12411959}, Title = {Quantal events shape cerebellar interneuron firing}, Uuid = {A8542972-A04C-429B-9930-EA137BDC3BE8}, Volume = {5}, Year = {2002}, url = {papers/Carter_NatNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn970}} @article{Carter:2004, Abstract = {Striatal medium spiny neurons (MSNs) in vivo undergo large membrane depolarizations known as state transitions. Calcium (Ca) entry into MSNs triggers diverse downstream cellular processes. However, little is known about Ca signals in MSN dendrites and spines and how state transitions influence these signals. Here, we develop a novel approach, combining 2-photon Ca imaging and 2-photon glutamate uncaging, to examine how voltage-sensitive Ca channels (VSCCs) and ionotropic glutamate receptors contribute to Ca signals in MSNs. We find that upstate transitions switch the VSCCs available in dendrites and spines, decreasing T-type while enhancing L-type channels. Moreover, these transitions change the dominant synaptic Ca source from Ca-permeable AMPA receptors to NMDA receptors. Finally, pairing bAPs with synaptic inputs generates additional synaptic Ca signals due to enhanced Ca influx through NMDA receptors. By altering the sources, amplitude, and kinetics of spine Ca signals, state transitions may gate synaptic plasticity and gene expression in MSNs.}, Author = {Carter, Adam G. and Sabatini, Bernardo L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Excitatory Amino Acid Antagonists;Calcium Channel Blockers;Electric Stimulation;Calcium Signaling;Synapses;Corpus Striatum;Rats;Animals;Microscopy, Confocal;research support, u.s. gov't, p.h.s. ;Patch-Clamp Techniques;Dendritic Spines;in vitro ;Drug Combinations;comparative study ;Calcium;Tetrodotoxin;research support, non-u.s. gov't ;Glutamates;Magnesium;21 Neurophysiology;Neurons;Membrane Potentials;24 Pubmed search results 2008;Dose-Response Relationship, Radiation;Excitatory Postsynaptic Potentials}, Month = {10}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {483-93}, Pii = {S0896627304006725}, Pubmed = {15504328}, Title = {State-dependent calcium signaling in dendritic spines of striatal medium spiny neurons}, Uuid = {06E91BE0-F5A4-4F7F-ACF4-E8A1C41F4A92}, Volume = {44}, Year = {2004}, url = {papers/Carter_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.10.013}} @article{Castejon:2005, Abstract = {The inflammatory reaction surrounding hemorrhagic and perihematomal brain parenchyma has been studied by means of light and transmission electron microscopy in 12 patients with severe traumatic head injuries complicated with subdural or extradural hematoma or hygroma. Perivascular cells, ameboid phagocytic microglial cells, and infiltrated macrophage/monocyte system were observed surrounding perivascular and intraparenchymal hemorrhagic foci. They showed phagocytic activity of degenerated nerve cell processes, and organized proteinaceous edema fluid present in the enlarged extracellular space. Endocytosis by means of clathrin coated vesicles also was observed. Facultative and professional phagocytes exhibited a full repertoire of lysosomes, phagosomes containing nerve cell debris, lipid droplets, and lipofucsin granules. Phagocytic pericytes remaining within the capillary basement membrane were also observed around perivascular hemorrhages. The inflammatory reaction was examined in young and old patients with an evolution time of brain injury ranging from 1 day to 2 years. The inflammatory process developed according to the intensity of traumatic insult, patient age, associated hematoma or hygroma, severity of vasogenic and cytotoxic oedema, and anoxic-ischemic conditions of brain parenchyma.}, Author = {Castej{\'o}n, O. J. and Castellano, A. and Arismendi, G. J. and Medina, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {1122-9497}, Journal = {J Submicrosc Cytol Pathol}, Keywords = {11 Glia;24 Pubmed search results 2008}, Medline = {102464197}, Month = {4}, Nlm_Id = {8804312}, Number = {1}, Organization = {Institute of Biological Investigations, Faculty of Medicine, University of Zulia, Maracaibo, Venezuela. ocastejo\@cantv.net}, Pages = {43-52}, Pubmed = {16136727}, Title = {The inflammatory reaction in human traumatic oedematous cerebral cortex}, Uuid = {E17FB550-B18D-49DD-8B99-52B57FDED32A}, Volume = {37}, Year = {2005}} @article{Castro:2001, Abstract = {Human cortical malformations often result in severe forms of epilepsy. Although the morphological properties of cells within these malformations are well characterized, very little is known about the function of these cells. In rats, prenatal methylazoxymethanol (MAM) exposure produces distinct nodules of disorganized pyramidal-like neurons (e.g., nodular heterotopia) and loss of lamination in cortical and hippocampal structures. Hippocampal nodular heterotopias are prone to hyperexcitability and may contribute to the increased seizure susceptibility observed in these animals. Here we demonstrate that heterotopic pyramidal neurons in the hippocampus fail to express a potassium channel subunit corresponding to the fast, transient A-type current. In situ hybridization and immunohistochemical analysis revealed markedly reduced expression of Kv4.2 (A-type) channel subunits in heterotopic cell regions of the hippocampus of MAM-exposed rats. Patch-clamp recordings from visualized heterotopic neurons indicated a lack of fast, transient (I(A))-type potassium current and hyperexcitable firing. A-type currents were observed on normotopic pyramidal neurons in MAM-exposed rats and on interneurons, CA1 pyramidal neurons, and cortical layer V-VI pyramidal neurons in saline-treated control rats. Changes in A-current were not associated with an alteration in the function or expression of delayed, rectifier (Kv2.1) potassium channels on heterotopic cells. We conclude that heterotopic neurons lack functional A-type Kv4.2 potassium channels and that this abnormality could contribute to the increased excitability and decreased seizure thresholds associated with brain malformations in MAM-exposed rats.}, Author = {Castro, P. A. and Cooper, E. C. and Lowenstein, D. H. and Baraban, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Methylazoxymethanol Acetate;Epilepsy;Disease Models, Animal;24 Pubmed search results 2008;Immunohistochemistry;Shab Potassium Channels;Cerebral Cortex;Animals;Hippocampus;Research Support, U.S. Gov't, P.H.S.;In Vitro;Potassium;Pregnancy;RNA, Messenger;In Situ Hybridization;Delayed Rectifier Potassium Channels;21 Epilepsy;Prenatal Exposure Delayed Effects;Shal Potassium Channels;21 Dysplasia-heterotopia;Pyramidal Cells;Action Potentials;Rats;Patch-Clamp Techniques;Dose-Response Relationship, Drug;Female;Potassium Channels;21 Neurophysiology;Potassium Channels, Voltage-Gated;Somatosensory Cortex;4-Aminopyridine;Choristoma;Tetraethylammonium;Research Support, Non-U.S. Gov't}, Medline = {21408159}, Month = {9}, Nlm_Id = {8102140}, Number = {17}, Organization = {Department of Neurological Surgery, The Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, California 94143, USA.}, Pages = {6626-34}, Pii = {21/17/6626}, Pubmed = {11517252}, Title = {Hippocampal heterotopia lack functional Kv4.2 potassium channels in the methylazoxymethanol model of cortical malformations and epilepsy}, Uuid = {EBA2A917-91DF-450C-ABAA-D30E6671A98B}, Volume = {21}, Year = {2001}} @article{Castro:2002, Abstract = {Cortical malformations resulting from aberrant brain development can be associated with mental retardation, dyslexia, and intractable forms of epilepsy. Despite emerging interest in the pathology and etiology of cortical malformations, little is known about the phenotype of cells within these lesions. In utero exposure to the DNA methylating agent methylazoxymethanol acetate (MAM) during a critical stage in neurodevelopment results in animals with distinct clusters of displaced neurons in hippocampus, i.e. nodular heterotopia. Here we examined the molecular and electrophysiological properties of cells within hippocampal heterotopia using rats exposed to MAM during gestation. Molecular analysis revealed that heterotopic cells do not express mRNA markers normally found in hippocampal pyramidal cells or dentate granule cells (SCIP, Math-2, Prox-1, neuropilin-2). In contrast, Id-2 mRNA, normally abundant in Layer II-III supragranular neocortical neurons but not in CA1 pyramidal neurons, was prominently expressed in hippocampal heterotopia. Current-clamp analysis of the firing properties of heterotopic neurons revealed a striking similarity with supragranular cortical neurons. In particular, both cells were characterized by small hyperpolarizing 'sag' potentials, high input resistance values, slow spike-train afterhyperpolarizations, and the absence of a depolarizing afterpotential. Normotopic CA1 pyramidal neurons (e.g. pyramidal cells with normal lamination adjacent to a heterotopia) in the MAM brain exhibited molecular and electrophysiological properties that were nearly identical to those of age-matched CA1 pyramidal neurons from control rats.We conclude that neuronal heterotopiae in the hippocampus of MAM-exposed rats are comprised of neurons with a Layer II-III supragranular cortex phenotype. The MAM model, therefore, may serve as a useful tool in examination of the factors influencing aberrant brain development and epilepsy.}, Author = {Castro, P. A. and Pleasure, S. J. and Baraban, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Pregnancy;Transcription Factors;Animals;Rats;Basic Helix-Loop-Helix Transcription Factors;Patch-Clamp Techniques;Homeodomain Proteins;Female;Rats, Sprague-Dawley;Neuropilin-2;RNA, Messenger;21 Dysplasia-heterotopia;Hippocampus;Brain Diseases;Octamer Transcription Factor-6;Cell Movement;21 Epilepsy;Research Support, U.S. Gov't, P.H.S.;Action Potentials;Cerebral Cortex;21 Neurophysiology;24 Pubmed search results 2008;Gene Expression;Choristoma;Research Support, Non-U.S. Gov't}, Medline = {22267563}, Nlm_Id = {7605074}, Number = {4}, Organization = {Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, Box 0520, 513 Parnassus Avenue, 94143, USA.}, Pages = {961-72}, Pii = {S0306452202002968}, Pubmed = {12379251}, Title = {Hippocampal heterotopia with molecular and electrophysiological properties of neocortical neurons}, Uuid = {E236F22F-D38E-4895-887A-89A27A49E4AC}, Volume = {114}, Year = {2002}, url = {papers/Castro_Neuroscience2002.pdf}} @article{Catapano:2004, Abstract = {Cellular repair of neuronal circuitry affected by neurodegenerative disease or injury may be approached in the adult neocortex via transplantation of neural precursors ("neural stem cells") or via molecular manipulation and recruitment of new neurons from endogenous precursors in situ. A major challenge for potential future approaches to neuronal replacement will be to specifically direct and control progressive differentiation, axonal projection and connectivity of neural precursors along a specific neuronal lineage. This goal will require a progressively more detailed understanding of the molecular controls over morphologic differentiation of specific neuronal lineages, including neurite outgrowth and elongation, in order to accurately permit and direct proper neuronal integration and connectivity. Here, we investigate controls over the morphologic differentiation of a specific prototypical lineage of cortical neurons: callosal projection neurons (CPN). We highly enriched CPN to an essentially pure population, and cultured them at three distinct stages of development from embryonic and postnatal mouse cortex by retrograde fluorescence labelling, followed by fluorescence-activated cell sorting. We find that specific peptide growth factors exert direct stage-specific positive and negative effects over the morphologic differentiation and process outgrowth of CPN. These effects are distinct from the effects of these growth factors on CPN survival [Catapano et al. (2001)J. Neurosci., 21, 8863-8872]. These data may be critical for the future goal of directing lineage-specific neuronal differentiation of transplanted or endogenous precursors/"stem cells" toward cellular repair of complex cortical circuitry.}, Author = {Catapano, Lisa A. and Arlotta, Paola and Cage, Tene A. and Macklis, Jeffrey D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Cell Differentiation;Apoptosis;Cell Survival;Immunohistochemistry;Male;Animals;Cells, Cultured;Flow Cytometry;Research Support, U.S. Gov't, P.H.S.;Proto-Oncogene Proteins;Bromodeoxyuridine;Fibroblast Growth Factor 2;Pregnancy;Cell Polarity;Neurofilament Proteins;Dendrites;Neocortex;Brain-Derived Neurotrophic Factor;Axons;Laterality;Comparative Study;Aging;Corpus Callosum;17 Transplant Regeneration;Proto-Oncogene Proteins c-bcl-2;Neurotrophin 3;Female;Embryo;Time Factors;Animals, Newborn;Cell Size;01 Adult neurogenesis general;Mice, Knockout;Mice;Neurons;Polymerase Chain Reaction;Research Support, Non-U.S. Gov't}, Month = {5}, Nlm_Id = {8918110}, Number = {9}, Organization = {Departments of Neurosurgery and Neurology, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.}, Pages = {2421-34}, Pii = {EJN3303}, Pubmed = {15128396}, Title = {Stage-specific and opposing roles of BDNF, NT-3 and bFGF in differentiation of purified callosal projection neurons toward cellular repair of complex circuitry}, Uuid = {24C8BB7C-71A6-44C1-AA77-C87F3C0481E4}, Volume = {19}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.0953-816X.2004.03303.x}} @article{Catapano:2001, Abstract = {Repair of specific neuronal circuitry in the neocortex may be possible via neural precursor transplantation or manipulation of endogenous precursors in situ. These approaches will almost certainly require a detailed understanding of the mechanisms that control survival and differentiation of specific neuronal lineages. Such analysis has been hampered by the overwhelming diversity of neuronal types intermixed in neocortex and the inability to isolate individual lineages. To elucidate stage-specific controls over the survival of individual lineages of cortical neurons, we purified immature callosal projection neurons (CPN) at distinct stages of development from embryonic and postnatal mouse cortex by retrograde fluorescence labeling, followed by fluorescence-activated cell sorting. Purified CPN survive well in culture, acquire stage-specific projection neuron morphologies, and express appropriate neurotransmitters and growth factor receptors. Purified CPN are dependent on exogenous trophic support for survival in a stage-specific manner. Survival of postnatal day 2 (P2) to P3 and P6-P7 CPN is promoted by overlapping but distinct sets of neurotrophic factors, whereas embryonic day 19 CPN show less specificity of dependence on peptide factors. These studies demonstrate for the first time the stage-specific control by peptide growth factors over the survival of a specific cortical neuronal lineage. Such information may be critical for the future goal of directed differentiation of transplanted or endogenous precursors toward cellular repair of complex cortical circuitry. 1529-2401 Journal Article}, Author = {Catapano, L. A. and Arnold, M. W. and Perez, F. A. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;10 Development;Cell Separation;Animals;Cells, Cultured;Cell Lineage/drug effects/physiology;Nerve Growth Factors/*metabolism/pharmacology;Cell Survival/drug effects/physiology;Cerebral Cortex/drug effects/*embryology/*metabolism;Mice, Inbred C57BL;Microspheres;Support, Non-U.S. Gov't;Culture Media, Conditioned/pharmacology;Axons/metabolism;D, F pdf;06 Adult neurogenesis injury induced;Cell Differentiation/drug effects/physiology;Flow Cytometry;Support, U.S. Gov't, P.H.S.;Mice;Neurons/cytology/drug effects/*metabolism;Immunohistochemistry}, Number = {22}, Organization = {Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {8863-72}, Title = {Specific neurotrophic factors support the survival of cortical projection neurons at distinct stages of development}, Uuid = {6DD121C9-AC6C-4A8C-8FED-2AFD352DFA2D}, Volume = {21}, Year = {2001}, url = {papers/Catapano_JNeurosci2001.pdf}} @article{Catapano:1999, Abstract = {In the current experiments, we address the emerging hypothesis that transplanted neural precursor cells can respond to local microenvironmental signals in the post-developmental brain and exhibit patterns of differentiation that depend critically on specific location within the brain. HiB5 precursor cells were transplanted into adult mouse cortex, corpus callosum, and multiple positions in striatum, and assessed for differentiation by morphology and immunocytochemistry. Our results indicate that the likelihood of both neuronal and glial differentiation of transplanted precursors depends on proximity to the medial striatum or subventricular zone of the adult host, supporting the concept that microenvironmental signals can critically affect the differentiation fate of neural precursors, and suggesting the potential to manipulate such signals in the adult brain.}, Author = {Catapano, L. A. and Sheen, V. L. and Leavitt, B. R. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Neuroreport}, Keywords = {Cell Differentiation;Transplantation, Heterologous;17 Transplant Regeneration;Neurons/*cytology/physiology/*transplantation;Immunohistochemistry;Rats;Human;L abstr;Autoradiography;Animal;Corpus Striatum/*physiology;Stem Cells/*cytology/physiology/*transplantation;Support, U.S. Gov't, P.H.S.;Cell Line, Transformed;Support, Non-U.S. Gov't;Mice;Cell Movement/physiology}, Number = {18}, Organization = {Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA.}, Pages = {3971-7.}, Title = {Differentiation of transplanted neural precursors varies regionally in adults striatum}, Uuid = {A1E361A1-0A65-4F03-BFA3-3E03098DDCF4}, Volume = {10}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10716243}} @article{Catsicas:1986, Abstract = {Central nervous system structures containing neurons labeled by the fluorescent tracers Fast blue (FB), Diamidino yellow dihydrochloride (DY), Rhodamine B isothiocyanate (RITC) and Rhodamine-labeled latex microspheres (RLM) were processed with the Golgi method. The goal was to improve the visualization of the fluorescent labeled neurons and to allow their ultrastructural examination. While the fluorescence of FB and RITC is greatly attenuated by the Golgi method, RLM and DY are still visible in Golgi-impregnated neurons. However, it is usually necessary to remove the silver precipitate by gold-toning.}, Author = {Catsicas, S. and Berbel, P. J. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Staining and Labeling;Rhodamines;Cats;Microscopy, Electron;Chick Embryo;Not relevant;Fluorescent Dyes;11 Glia;Fixatives;Animals;Microspheres;Support, Non-U.S. Gov't;Amidines;Neurons}, Medline = {87088404}, Month = {12}, Nlm_Id = {7905558}, Number = {4}, Pages = {325-32}, Pubmed = {2432364}, Title = {A combination of Golgi impregnation and fluorescent retrograde labeling}, Uuid = {A099D44A-1A82-4CA4-8DFC-5F2A69ACF8FB}, Volume = {18}, Year = {1986}} @article{Cattani:2007, Abstract = {Cell-surface glutamate transporters are essential for the proper function of early cortical networks because their dysfunction induces seizures in the newborn rat in vivo. We have now analyzed the consequences of their inhibition by dl-TBOA on the activity of the developing CA1 rat hippocampal network in vitro. dl-TBOA generated a pattern of recurrent depolarization with an onset and decay of several seconds' duration in interneurons and pyramidal cells. These slow network oscillations (SNOs) were mostly mediated by gamma-aminobutyric acid (GABA) in pyramidal cells and by GABA and N-methyl-d-aspartate (NMDA) receptors in interneurons. However, in both cell types SNOs were blocked by NMDA receptor antagonists, suggesting that their generation requires a glutamatergic drive. Moreover, in interneurons, SNOs were still generated after the blockade of NMDA-mediated synaptic currents with MK-801, suggesting that SNOs are expressed by the activation of extrasynaptic NMDA receptors. Long-lasting bath application of glutamate or NMDA failed to induce SNOs, indicating that they are generated by periodic but not sustained activation of NMDA receptors. In addition, SNOs were observed in interneurons recorded in slices with or without the strata pyramidale and oriens, suggesting that the glutamatergic drive may originate from the radiatum and pyramidale strata. We propose that in the absence of an efficient transport of glutamate, the transmitter diffuses in the extracellular space to activate extrasynaptic NMDA receptors preferentially present on interneurons that in turn activate other interneurons and pyramidal cells. This periodic neuronal coactivation may contribute to the generation of seizures when glutamate transport dysfunction is present.}, Author = {Cattani, Adriano Augusto and Bonfardin, Val{\'e}rie Delphine and Represa, Alfonso and Ben-Ari, Yehezkel and Aniksztejn, Laurent}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0375404}, Number = {4}, Organization = {INMED-INSERM U29, Universit{\'e} de la M{\'e}diterran{\'e}e, Parc Scientifique de Luminy, 13273 Marseille cedex 09, France. anik\@inmed.univ-mrs.fr).}, Pages = {2324-36}, Pii = {00378.2007}, Pubmed = {17634340}, Title = {Generation of slow network oscillations in the developing rat hippocampus after blockade of glutamate uptake}, Uuid = {2DA79670-8A30-4D9A-B729-71923AA68909}, Volume = {98}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00378.2007}} @article{Caviness:2003, Abstract = {The neurons of the neocortex are generated over a 6 day neuronogenetic interval that comprises 11 cell cycles. During these 11 cell cycles, the length of cell cycle increases and the proportion of cells that exits (Q) versus re-enters (P) the cell cycle changes systematically. At the same time, the fate of the neurons produced at each of the 11 cell cycles appears to be specified at least in terms of their laminar destination. As a first step towards determining the causal interrelationships of the proliferative process with the process of laminar specification, we present a two-pronged approach. This consists of (i) a mathematical model that integrates the output of the proliferative process with the laminar fate of the output and predicts the effects of induced changes in Q and P during the neuronogenetic interval on the developing and mature cortex and (ii) an experimental system that allows the manipulation of Q and P in vivo. Here we show that the predictions of the model and the results of the experiments agree. The results indicate that events affecting the output of the proliferative population affect both the number of neurons produced and their specification with regard to their laminar fate. 22648197 1047-3211 Evaluation Studies Journal Article Validation Studies}, Author = {Caviness, V. S. and Goto, T. and Tarui, T. and Takahashi, T. and Bhide, P. G. and Nowakowski, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Cereb Cortex}, Keywords = {10 Development;*Models, Neurological;Tissue Culture;Gene Expression Regulation, Developmental;Comparative Study;Cell Cycle/physiology;Animal;Neocortex/cytology/*embryology/*physiology;Microfilament Proteins/deficiency/genetics/*metabolism;Computer Simulation;Cell Division/physiology;Mice, Knockout;Epithelium/embryology;Support, Non-U.S. Gov't;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Cerebral Ventricles/cytology/embryology;Mice;F;Neurons/classification/cytology/*physiology}, Number = {6}, Organization = {Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.}, Pages = {592-8}, Pubmed = {12764033}, Title = {Cell output, cell cycle duration and neuronal specification: a model of integrated mechanisms of the neocortical proliferative process}, Uuid = {2C6DB246-B9F3-481D-B71C-E356B5C52798}, Volume = {13}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12764033}} @article{Caviness:1973, Abstract = {0021-9967 Journal Article}, Author = {Caviness, V. S. and Sidman, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {J Comp Neurol}, Keywords = {Thymidine;Cell Differentiation;*Neurons;Autoradiography;A,F abstr;Hippocampus/pathology;Animals;Mice;Cerebral Cortex/*pathology;Movement Disorders/genetics/*pathology}, Number = {2}, Pages = {141-51}, Pubmed = {4700506}, Title = {Time of origin or corresponding cell classes in the cerebral cortex of normal and reeler mutant mice: an autoradiographic analysis}, Uuid = {786EA724-BCC9-472F-97A5-28C0F42E27CC}, Volume = {148}, Year = {1973}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4700506}} @article{Caviness:1976, Abstract = {In the neocortex of the reeler mutant mouse, there is inversion in the normal relative positions of polymorphic and pyramidal cells and of large with respect to medium-sized and small pyramidal cells. Granule cells are concentrated at a near-normal mid-cortical level in the mutant. As in the normal animal, and despite cell malposition in reeler, the principal tangential fiber system lies in the zone of polymorphic cells. Large fiber fascicles, known from experimental studies to be principally thalamo-cortical afferents, enter the tangential fiber system in the polymorphic cell zone of both reeler and normal neocortex. In the mutant these fascicles must traverse the full width of the cortex to reach this fiber system in its superficial location. In both normal and mutant animals single fibers, again principally thalamo-cortical afferents, pass from the principal tangertial fiber system to ramify in a fiber feltwork in the zone of granule cells. In the mutant these descend whereas in the normal animal they ascend. Also, as in the normal mouse, single fibers pass radially between all levels of the mutant cortex and the central white matter. Regional variations in the character, the pattern of distribution and the relative prominence of homologous cell and fiber elements are closely parallel in reeler and normal. This suggests that cell differentiation and the tangenital organization of reeler neocortex are normal despite cell malposition in the mutant.}, Author = {Caviness, V. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Mutation;Nerve Fibers;10 Development;Female;10 genetics malformation;research support, u.s. gov't, p.h.s.;Animals;Male;Cerebral Cortex;Mice;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {0406041}, Number = {4}, Pages = {435-47}, Pubmed = {1002868}, Title = {Patterns of cell and fiber distribution in the neocortex of the reeler mutant mouse}, Uuid = {DB13884A-C874-4276-B21C-4D21E40FDD39}, Volume = {170}, Year = {1976}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901700404}} @article{Caviness:1976a, Abstract = {The tangential organization of the callosal system of interhemispheric connections, as judged by the distribution of axon terminals as well as by the distribution of cells of origin of callosal axons, is normal in the reeler mutant mouse. As in the normal animal connections between the two cerebral hemispheres are homotopic. In the reeler, as in the normal animal, medium-sized pyramidal cells are, numerically speaking, the principal cells of origin of the callosal system. These lie superficially in the cortex of the normal animal but deep within the cortex of reeler. Callosal terminals are most densely concentrated at the cortical level of the small and medium-sized pyramids in both reeler and normal animals. It is probable, therefore, that the same classes of neurons are interconnected by the callosal system in the normal and reeler mouse despite malposition of neurons in reeler. The patterns of intracortical distribution of terminals of callosal axons is evidently governed by the positions of their target cells.}, Author = {Caviness, V. S. and Yorke, C. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Mice;Mutation;24 Pubmed search results 2008;10 Development;Nerve Degeneration;Axonal Transport;Female;Neural Pathways;10 genetics malformation;research support, u.s. gov't, p.h.s.;Animals;Horseradish Peroxidase;Cerebral Cortex;Male;Corpus Callosum}, Month = {12}, Nlm_Id = {0406041}, Number = {4}, Pages = {449-59}, Pubmed = {63471}, Title = {Interhemispheric neocortical connections of the corpus callosum in the reeler mutant mouse: a study based on anterograde and retrograde methods}, Uuid = {FAFAF299-9CB1-4C5A-8193-1C969C67EA39}, Volume = {170}, Year = {1976}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901700405}} @article{Caviness:1995, Abstract = {The number of neurons in the neocortex is the product of the size of the preneuronogenetic founder population, that is, the number of proliferative cells that are present at the onset of neuronogenesis, and neuronogenetic amplification occurring as neurons are being produced. The amount of neuronogenetic amplification is determined by changes in the output fraction, Q, from 0 to 1, over a fixed number of cell cycles. Greater neuronogenetic amplification would occur across species if the number of cell cycles during which Q <0.5 increased. Since neither the length of the cell cycle nor the length of the neuronogenetic interval, that is, time per se, influence neuron number directly, it is speculated that changes in these parameters are essential to neuronal diversity. 0166-2236 Journal Article Review Review, Tutorial}, Author = {Caviness, V. S. and Takahashi, T. and Nowakowski, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Trends Neurosci}, Keywords = {Models, Biological;Human;Support, U.S. Gov't, Non-P.H.S.;Cerebral Cortex/*anatomy &histology/growth &development/physiology;N;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;*Evolution;19 Neocortical evolution}, Number = {9}, Organization = {Dept of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.}, Pages = {379-83}, Pubmed = {7482802}, Title = {Numbers, time and neocortical neuronogenesis: a general developmental and evolutionary model}, Uuid = {AC343C45-CC45-4FC6-9F32-BA585E9EEA15}, Volume = {18}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7482802}} @article{Cayouette:2003, Abstract = {Asymmetric segregation of cell-fate determinants during cell division plays an important part in generating cell diversity in invertebrates. We showed previously that cells in the neonatal rat retina divide at various orientations and that some dividing cells asymmetrically distribute the cell-fate determinant Numb to the two daughter cells. Here, we test the possibility that such asymmetric divisions contribute to retinal cell diversification. We have used long-term videomicroscopy of green-fluorescent-protein (GFP)-labeled retinal explants from neonatal rats to visualize the plane of cell division and follow the differentiation of the daughter cells. We found that cells that divided with a horizontal mitotic spindle, where both daughter cells should inherit Numb, tended to produce daughters that became the same cell type, whereas cells that divided with a vertical mitotic spindle, where only one daughter cell should inherit Numb, tended to produce daughters that became different. Moreover, overexpression of Numb in the dividing cells promoted the development of photoreceptor cells at the expense of interneurons and Muller glial cells. These findings indicate that the plane of cell division influences cell-fate choice in the neonatal rat retina and support the hypothesis that the asymmetric segregation of Numb normally influences some of these choices. 22588265 0950-1991 Journal Article}, Author = {Cayouette, M. and Raff, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:51 -0400}, Journal = {Development}, Keywords = {Microscopy, Video;Cell Differentiation;Tissue Culture;10 Development;Rats;Photoreceptors, Vertebrate/cytology;Mitosis;Recombinant Proteins/genetics;Models, Biological;Animal;Rats, Sprague-Dawley;Nerve Tissue Proteins/genetics;Animals, Newborn;Support, Non-U.S. Gov't;Interneurons/cytology;Eye Proteins/genetics;Retina/*cytology/*growth &development/metabolism;Cell Division;Luminescent Proteins/genetics;F}, Number = {11}, Organization = {MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, London WC1E 6BT, UK. m.cayouette\@stanford.edu}, Pages = {2329-39}, Pubmed = {12702648}, Title = {The orientation of cell division influences cell-fate choice in the developing mammalian retina}, Uuid = {ABBAC658-12A9-4D86-9EF9-012C878D715D}, Volume = {130}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12702648}} @article{Cayouette:2002, Abstract = {It is a major challenge to understand how the neuroepithelial cells of the developing CNS choose between alternative cell fates to generate cell diversity. In invertebrates such as Drosophila melanogaster and Caenorhabditis elegans, asymmetric segregation of cell-fate determining proteins or mRNAs to the two daughter cells during precursor cell division plays a crucial part in cell diversification. There is increasing evidence that this mechanism also operates in vertebrate neural development and that Numb proteins, which function as cell-fate determinants during Drosophila development, may also function in this way in vertebrates. Recent studies on mouse cortical progenitor cells have provided the strongest evidence yet that this is the case. Here, we review these and other findings that suggest an important role for the asymmetric segregation of Numb proteins in vertebrate neural development. 22337315 1097-6256 Journal Article Review Review, Tutorial}, Author = {Cayouette, M. and Raff, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Nat Neurosci}, Keywords = {Drosophila/embryology/metabolism;10 Development;Mammals/embryology/metabolism;Human;Neurons/*cytology/metabolism;Animal;Membrane Proteins/genetics/*metabolism;Cell Lineage/*genetics;F;Nerve Tissue Proteins/genetics/*metabolism;Central Nervous System/cytology/*embryology/metabolism;Support, Non-U.S. Gov't;Cell Division/*genetics;Cell Differentiation/*genetics;Stem Cells/*cytology/metabolism}, Number = {12}, Organization = {MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, University College London, Gower Street, London WC1E 6BT, UK. m.cayouette\@stanford.edu}, Pages = {1265-9}, Pubmed = {12447381}, Title = {Asymmetric segregation of Numb: a mechanism for neural specification from Drosophila to mammals}, Uuid = {3E581062-C6E6-4E1C-8264-294F0876AD5D}, Volume = {5}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12447381}} @article{Cayre:2001, Abstract = {In the house cricket (Acheta domesticus) mushroom bodies, neurogenesis still occurs during adulthood. Using in vitro approaches, the respective roles of natural polyamines in neurogenesis were examined. Mushroom body neuroblast proliferation was assayed in organotypic culture using 5-bromo, 2'-deoxyuridine labeling. The number of labeled cells was significantly increased when putrescine was added to culture medium, whereas spermidine and spermine supplementation did not alter cell proliferation. Conversely, in vitro morphometric studies on mushroom body neurons cultured in a defined medium showed that putrescine addition failed to alter any morphological character of these interneurons, whereas addition of the long-chain polyamines, spermidine and spermine, stimulated neuron differentiation. These two polyamines significantly increased total neurite length; moreover, spermidine-treated cells exhibited more branches than the controls. The present data demonstrate that putrescine has a mitogenic effect on mushroom body neuronal precursors, and that spermidine and spermine, which failed to induce neuroblast proliferation, act on neuronal differentiation, inducing neurite outgrowth. Our results indicate that short- and long-chain polyamines play specific roles during neurogenesis, and provide a basis for further studies on neuronal precursor proliferation and differentiation. Copyright 2001 John Wiley &Sons, Inc.}, Author = {Cayre, M. and Malaterre, J. and Strambi, C. and Charpin, P. and Ternaux, J. P. and Strambi, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:43 -0400}, Journal = {J Neurobiol}, Keywords = {C pdf;04 Adult neurogenesis factors}, Number = {4}, Organization = {Laboratoire de Neurobiologie, CNRS, 31 Chemin Joseph Aiguier, 13402 Marseille cedex 20, France.}, Pages = {315-24.}, Title = {Short- and long-chain natural polyamines play specific roles in adult cricket neuroblast proliferation and neuron differentiation in vitro}, Uuid = {94AA8BE7-E491-44C5-8FD1-C7E78FDE069F}, Volume = {48}, Year = {2001}, url = {papers/Cayre_JNeurobiol2001.pdf}} @article{Cayre:2006, Abstract = {Adult neural stem cells in the subventricular zone (SVZ) produce neuronal progenitors that migrate along the rostral migratory stream (RMS) and generate olfactory interneurons. Here, we evaluate the migratory potential of SVZ cells outside the RMS and their capacity to generate oligodendrocytes in the adult brain. We show that SVZ cells migrate long distances when grafted into white matter tracts such as the cingulum (Ci) and corpus callosum (CC). Furthermore, 22 days postinjection, most present morphologic and phenotypic characteristics of cells committed to the oligodendrocyte lineage. Cells grafted in shiverer CC and Ci become MBP-positive oligodendrocytes, abundantly myelinating these white matter tracts. Type A progenitors are involved in this myelinating process. Altogether, this study reveals the migrating and myelinating potential of SVZ cells in a new environmental context. Therefore, SVZ cells stand as interesting candidates for the development of novel therapeutic strategies for demyelinating diseases.}, Author = {Cayre, Myriam and Bancila, Mircea and Virard, Isabelle and Borges, Ana and Durbec, Pascale}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9100095}, Number = {4}, Organization = {UMR 6216, Institut de Biologie du D{\'e}veloppement de Marseille Luminy, Case 907, 13288 Marseille Cedex 9, France.}, Pages = {748-58}, Pii = {S1044-7431(06)00006-6}, Pubmed = {16481195}, Title = {Migrating and myelinating potential of subventricular zone neural progenitor cells in white matter tracts of the adult rodent brain}, Uuid = {A699B43E-148A-4F14-BE99-7DC3468E5468}, Volume = {31}, Year = {2006}, url = {papers/Cayre_MolCellNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2006.01.004}} @article{Cecchi:2001, Abstract = {Adult neurogenesis has long been documented in the vertebrate brain and recently even in humans. Although it has been conjectured for many years that its functional role is related to the renewing of memories, no clear mechanism as to how this can be achieved has been proposed. Using the mammalian olfactory bulb as a paradigm, we present a scheme in which incorporation of new neurons proceeds at a constant rate, while their survival is activity-dependent and thus contingent on new neurons establishing suitable connections. We show that a simple mathematical model following these rules organizes its activity so as to maximize the difference between its responses and can adapt to changing environmental conditions in unsupervised fashion, in agreement with current neurophysiological data.}, Author = {Cecchi, G. A. and Petreanu, L. T. and Alvarez-Buylla, A. and Magnasco, M. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Comput Neurosci}, Keywords = {01 Adult neurogenesis general;A abstr}, Number = {2}, Organization = {Laboratory of Mathematical Physics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, U.S.A.; Functional Neuroimaging Laboratory, Weill Medical College of Cornell University, New York, NY 10021 and Biometaphorical Computing Group, TJ Watson Center, IBM Research, Yorktown Heights, NY 10598, USA. Email: gcecchi\@us.ibm.com}, Pages = {175-182.}, Title = {Unsupervised Learning and Adaptation in a Model of Adult Neurogenesis}, Uuid = {E50C2E4C-B5D4-4595-99F4-F5F323B517A6}, Volume = {11}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11717533}} @article{Cepko:1999, Abstract = {A fundamental issue concerning development of the vertebrate retina is the relative contributions of extrinsic and intrinsic cues to the determination of cell fate. Recent findings suggest that retinal progenitors go through a series of changes in intrinsic properties that control their competence to make different cell types and that extrinsic cues influence the ratios of the cell types that they produce. Recent studies of the role of the basic helix-loop-helix genes in retinal development have indicated that they can regulate competence and/or other aspects of cell fate determination.}, Author = {Cepko, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Retina;10 Development;21 Neurophysiology;Helix-Loop-Helix Motifs;Rats;Chick Embryo;Stem Cells;Embryonic Induction;21 Activity-development;Photoreceptors, Vertebrate;Animals;Mice;24 Pubmed search results 2008;review}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Department of Genetics Howard Hughes Medical Institute Harvard Medical School 200 Longwood Avenue Boston Massachusetts 02115 USA.}, Pages = {37-46}, Pii = {S0959-4388(99)80005-1}, Pubmed = {10072376}, Title = {The roles of intrinsic and extrinsic cues and bHLH genes in the determination of retinal cell fates}, Uuid = {F2A9DB1A-26FB-44D1-9458-A79A05E830BD}, Volume = {9}, Year = {1999}, url = {papers/Cepko_CurrOpinNeurobiol1999.pdf}} @article{Cepko:2001, Author = {Cepko, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:43 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {23 Technique;Gene Expression Regulation, Developmental;Human;Oligonucleotide Array Sequence Analysis;Molecular Biology;review, tutorial;DNA, Complementary;Animals;Brain;Central Nervous System Diseases;review;Cell Lineage}, Medline = {21547538}, Month = {11}, Nlm_Id = {9809671}, Organization = {Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. cepko\@genetics.med.harvard.edu}, Pages = {1159-60}, Pii = {nn1101-1159}, Pubmed = {11687824}, Title = {Tackling the brain's genetic complexity}, Uuid = {44DF9009-2AD8-44B0-A718-71048E6706BA}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Cepko_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1101-1159}} @article{Cernak:2002, Abstract = {Few studies have characterised apoptosis in a brain injury model that causes a significant degree of diffuse axonal injury. Such characterisation is essential from a clinical viewpoint since diffuse axonal injury is a major component of human head injury. The present study therefore, examines the expression of active and proactive caspase-3, and the bax, bcl-2 and bcl-x members of the bcl-2 family, to characterise the temporal profile of apoptosis in a model of traumatic brain injury in rats that produces significant diffuse axonal injury. Pentobarbital anaesthetised male Sprague-Dawley rats were injured using the 2m impact-acceleration model of diffuse traumatic brain injury. After injury, diffuse trauma resulted in an increased bax expression followed by induction of caspase-3. The increase in caspase-3 was simultaneous with an increase in anti-apoptotic bcl-2 expression. Bcl-x levels were increased after induction of caspase-3 and the increased levels of bcl-x were sustained to the end of the 5-day observation period. Increased active caspase-3 expression was associated with the appearance of TUNEL positive cells. These cells were detected in different brain regions at different times, with some regions showing no apoptotic cells until 3 days after injury. No TUNEL positive cells were detected at 7 and 14 days after injury. DNA electrophoresis confirmed that DNA fragmentation was maximal at 3 days after injury. Increased active caspase-3 levels were also significantly correlated with increased bcl-2 levels (r=0.80; P<0.001) suggesting that the apoptotic cascade after diffuse traumatic brain injury is a carefully controlled cellular homeostatic response. Pharmacological manipulation of this balance may offer a therapeutic approach for preventing cell death and improving outcome after diffuse traumatic brain injury. 0967-5868 Journal Article}, Author = {Cernak, I. and Chapman, S. M. and Hamlin, G. P. and Vink, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Clin Neurosci}, Keywords = {Proto-Oncogene Proteins c-bcl-2/biosynthesis;Animals;Neurons/pathology;Brain Injuries/*pathology;Rats;Electrophoresis, Agar Gel;Apoptosis/*physiology;D pdf;Rats, Sprague-Dawley;Male;Immunoblotting;Proto-Oncogene Proteins/biosynthesis;Support, Non-U.S. Gov't;In Situ Nick-End Labeling;06 Adult neurogenesis injury induced;Immunohistochemistry;Caspases/biosynthesis;DNA Fragmentation}, Number = {5}, Organization = {Department of Neuroscience, Georgetown University, Washington, DC, USA.}, Pages = {565-72}, Pubmed = {12383417}, Title = {Temporal characterisation of pro- and anti-apoptotic mechanisms following diffuse traumatic brain injury in rats}, Uuid = {70775058-6D6C-4E7F-A9F5-6BA58738903B}, Volume = {9}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12383417}} @article{Chae:1997, Abstract = {The adult mammalian cortex is characterized by a distinct laminar structure generated through a well-defined pattern of neuronal migration. Successively generated neurons are layered in an "inside-out" manner to produce six cortical laminae. We demonstrate here that p35, the neuronal-specific activator of cyclin-dependent kinase 5, plays a key role in proper neuronal migration. Mice lacking p35, and thus p35/cdk5 kinase activity, display severe cortical lamination defects and suffer from sporadic adult lethality and seizures. Histological examination reveals that the mutant mice lack the characteristic laminated structure of the cortex. Neuronal birth-dating experiments indicate a reversed packing order of cortical neurons such that earlier born neurons reside in superficial layers and later generated neurons occupy deep layers. The phenotype of p35 mutant mice thus demonstrates that the formation of cortical laminar structure depends on the action of the p35/cdk5 kinase.}, Author = {Chae, T. and Kwon, Y. T. and Bronson, R. and Dikkes, P. and Li, E. and Tsai, L. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Animals;Humans;Seizures;Open Reading Frames;Protein-Serine-Threonine Kinases;Gene Deletion;Genomic Library;Mice, Neurologic Mutants;Embryonic and Fetal Development;Crosses, Genetic;Cerebral Cortex;Neurons;Recombination, Genetic;Mice, Knockout;10 genetics malformation;Polymerase Chain Reaction;research support, u.s. gov't, p.h.s.;Mice;Cyclin-Dependent Kinase 5;Cyclin-Dependent Kinases;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {29-42}, Pii = {S0896-6273(01)80044-1}, Pubmed = {9010203}, Title = {Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality}, Uuid = {94101B09-067D-436C-ABB9-3F910F8A9A29}, Volume = {18}, Year = {1997}} @article{Chaisuksunt:2000, Abstract = {Some neurons in the brain and spinal cord will regenerate axons into a living peripheral nerve graft inserted at the site of injury, others will not. We have examined the patterns of expression of four molecules thought to be involved in developmental and regenerative axonal growth, in the cerebellum and brainstem of adult rats, following the implantation into the cerebellum of peripheral nerve grafts. We also determined how the expression patterns observed correlate with the abilities of neurons in these regions to regenerate axons. Three days to 16 weeks after insertion of living tibial nerve autografts, neurons which had regenerated axons into the graft were retrogradely labelled from the distal extremity of the graft with cholera toxin conjugated to horseradish peroxidase, and sections through the cerebellum and brainstem were processed for visualization of transported tracer and/or hybridized with riboprobes to detect messenger RNAs for the cell recognition molecules L1 and CHL1 (close homologue of L1), growth-associated protein-43 and the cellular oncogene c-jun. Retrogradely labelled neurons were present in cerebellar deep nuclei close to the graft and in brainstem nuclei known to project to the cerebellum. Neurons in these same nuclei were found to have up-regulated expression of all four messenger RNAs. Individual retrogradely labelled neurons also expressed high levels of L1, CHL1, c-jun or growth-associated protein-43 messenger RNAs (and vice versa), and every messenger RNA investigated was co-localized with at least one other messenger RNA. Purkinje cells did not regenerate axons into the graft or up-regulate L1, CHL1 or growth-associated protein-43 messenger RNAs, but there was increased expression of c-jun messenger RNA in some Purkinje cells close to the graft. Freeze-killed grafts produced no retrograde labelling of neurons, and resulted in only transient and low levels of up-regulation of the tested molecules, mainly L1 and CHL1.These findings show that cerebellar deep nucleus neurons and precerebellar brainstem neurons, but not Purkinje cells, have a high propensity for axon regeneration, and that axonal regeneration by these neurons is accompanied by increased expression of L1, CHL1, c-jun and growth-associated protein-43. Furthermore, although the patterns of expression of the four molecules investigated are not identical in regenerating neuronal populations, it is probable that all four are up-regulated in all neurons whose axons regenerate into the grafts and that their up-regulation may be required for axon regeneration to occur. Finally, because c-jun up-regulation is seen in Purkinje cells close to the graft, unaccompanied by up-regulation of the other molecules investigated, c-jun up-regulation alone cannot be taken to reliably signify a regenerative response to axotomy.}, Author = {Chaisuksunt, V. and Zhang, Y. and Anderson, P. N. and Campbell, G. and Vaudano, E. and Schachner, M. and Lieberman, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Tibial Nerve;Neural Cell Adhesion Molecules;GAP-43 Protein;Purkinje Cells;Tissue Distribution;Animals;Leukocyte L1 Antigen Complex;Rats;Female;Axons;Rats, Sprague-Dawley;Reference Values;RNA, Messenger;Proto-Oncogene Proteins c-jun;Nerve Regeneration;Membrane Glycoproteins;Neurons;Cerebellum;Neural Cell Adhesion Molecule L1;24 Pubmed search results 2008;Brain Stem;Research Support, Non-U.S. Gov't}, Medline = {20453519}, Nlm_Id = {7605074}, Number = {1}, Organization = {Department of Anatomy and Developmental Biology, University College London, Gower Street, WC1E 6BT, London, UK.}, Pages = {87-108}, Pii = {S0306452200002542}, Pubmed = {10996461}, Title = {Axonal regeneration from CNS neurons in the cerebellum and brainstem of adult rats: correlation with the patterns of expression and distribution of messenger RNAs for L1, CHL1, c-jun and growth-associated protein-43}, Uuid = {0FD521FA-93BA-4F19-9D61-3EB8543E7667}, Volume = {100}, Year = {2000}} @article{Chambers:2001, Abstract = {The olfactory bulb, neocortex and archicortex arise from a common pool of progenitors in the dorsal telencephalon. We studied the consequences of supplying excess Notch1 signal in vivo on the cellular and regional destinies of telencephalic precursors using bicistronic replication defective retroviruses. After ventricular injections mid-neurogenesis (E14.5), activated Notch1 retrovirus markedly inhibited the generation of neurons from telencephalic precursors, delayed the emergence of cells from the subventricular zone (SVZ), and produced an augmentation of glial progeny in the neo- and archicortex. However, activated Notch1 had a distinct effect on the progenitors of the olfactory bulb, markedly reducing the numbers of cells of any type that migrated there. To elucidate the mechanism of the cell fate changes elicited by Notch1 signals in the cortical regions, short- and long-term cultures of E14.5 telencephalic progenitors were examined. These studies reveal that activated Notch1 elicits a cessation of proliferation that coincides with an inhibition of the generation of neurons. Later, during gliogenesis, activated Notch1 triggers a rapid cellular proliferation with a significant increase in the generation of cells expressing GFAP. To examine the generation of cells destined for the olfactory bulb, we used stereotaxic injections into the early postnatal anterior subventricular zone (SVZa). We observed that precursors of the olfactory bulb responded to Notch signals by remaining quiescent and failing to give rise to differentiated progeny of any type, unlike cortical precursor cells, which generated glia instead of neurons. These data show that forebrain precursors vary in their response to Notch signals according to spatial and temporal cues, and that Notch signals influence the composition of forebrain regions by modulating the rate of proliferation of neural precursor cells.}, Author = {Chambers, C. B. and Peng, Y. and Nguyen, H. and Gaiano, N. and Fishell, G. and Nye, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Development}, Keywords = {10 Development;Signal Transduction;Recombinant Fusion Proteins/metabolism;Embryo/cytology/metabolism;Cells, Cultured;Rats;Animal;Neurons/*metabolism;Retroviridae/genetics/metabolism;Prosencephalon/cytology/*embryology/metabolism;Microscopy, Fluorescence;Membrane Proteins/*metabolism;Genetic Vectors;Support, Non-U.S. Gov't;Cell Size;Support, U.S. Gov't, P.H.S.;Olfactory Bulb/cytology/embryology;Mice;Cell Division;Immunohistochemistry;Neuroglia/metabolism;Stem Cells/*metabolism;F;Genes, Reporter}, Number = {5}, Organization = {Departments of Molecular Pharmacology &Biological Chemistry, Northwestern University Medical School, Chicago, IL 60611, USA.}, Pages = {689-702.}, Title = {Spatiotemporal selectivity of response to Notch1 signals in mammalian forebrain precursors}, Uuid = {66DE6081-0136-48E7-B54A-97C295730010}, Volume = {128}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11171394%20http://www.biologists.com/Development/128/05/dev9653.html}} @article{Chan:2006, Abstract = {Despite intense study, the precise origin and cell lineage of microglia, the resident mononuclear phagocytes of the nervous system, are still a matter for debate. Unlike macroglia (astrocytes and oligodendrocytes) and neurons, which are derived from neuroectoderm, microglial progenitors arise from peripheral mesodermal (myeloid) tissue. The view still commonly held is that tissue-resident mononuclear phagocytes (including microglia) are derived from circulating blood monocytes and these take up residence late in gestation and postnatally. However, microglial progenitors colonise the nervous system primarily during embryonic and fetal periods of development. Recent evidence indicates differences between the lineage of mononuclear phagocytes during the embryonic and fetal period from that in the neonate and adult-mononuclear phagocytes that take up residence within tissues are derived from a lineage of myeloid cells that is independent of the monocyte lineage. Our own findings on the development and differentiation of microglial progenitors, taken together with findings by other investigators, and in the context of the heterogeneity between myeloid differentiation in the fetus and in the adult, support the view that microglia are derived prenatally from mesodermal progenitors that are distinct from monocytes. Furthermore, microglial progenitors colonise the nervous system via extravascular routes initially. These findings challenge the concept that resident microglia in the nervous system are derived from circulating blood monocytes. Work is still underway to establish the tissue of origin and lineage of microglial progenitors in vivo. This information is critical not only from a developmental perspective, but significantly from a therapeutic viewpoint, as (i) the unique property of microglial progenitors to colonise the nervous system from the periphery allows these cells to be exploited as a biological and non-invasive means for cell therapy by delivering genes to the nervous system (microglial engraftment), and (ii) there are indications that microglial progenitors are specifically able to home to the nervous system. Use of microglial progenitors for therapeutic purposes becomes feasible only if the origin and cell lineage of these microglial progenitors are known and these cells can be isolated and manipulated in vitro (i.e., to express specific trophic factors) prior to therapeutic transfer (e.g., intravenously) in vivo. In this paper, we shall briefly consider the existing concepts on the origin and lineage of microglial progenitors and discuss new hypotheses in the light of emerging data that suggest clear differences between fetal and adult ontogeny of myeloid cells.}, Author = {Chan, and Kohsaka, and Rezaie,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0165-0173}, Journal = {Brain Res Brain Res Rev}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8908638}, Organization = {Department of Anatomy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.}, Pii = {S0165-0173(06)00118-4}, Pubmed = {17188751}, Title = {The origin and cell lineage of microglia-New concepts}, Uuid = {FCE99306-B317-4A82-8B42-AEBC3C1860F9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainresrev.2006.11.002}} @article{Chanas-Sacre:2000, Abstract = {Radial glial cells play a major guidance role for migrating neurons during central nervous system (CNS) histogenesis but also play many other crucial roles in early brain development. Being among the earliest cells to differentiate in the early CNS, they provide support for neuronal migration during embryonic brain development; provide instructive and neurotrophic signals required for the survival, proliferation, and differentiation of neurons; and may be multipotential progenitor cells that give rise to various cell types, including neurons. Radial glial cells constitute a major cell type of the developing brain in numerous nonmammalian and mammalian vertebrates, increasing in complexity in parallel with the organization of the nervous tissue they help to build. In mammalian species, these cells transdifferentiate into astrocytes when neuronal migration is completed, whereas, in nonmammalian species, they persist into adulthood as a radial component of astroglia. Thus, our perception of radial glia may have to change from that of path-defining cells to that of specialized precursor cells transiently fulfilling a guidance role during brain histogenesis. In that respect, their apparent change of phenotype from radial fiber to astrocyte probably constitutes one of the most common transdifferentiation events in mammalian development.}, Author = {Chanas-Sacre, G. and Rogister, B. and Moonen, G. and Leprince, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci Res}, Keywords = {Cell Differentiation;Neuroglia/*physiology;Human;Phenotype;Animal;Cell Lineage/physiology;11 Glia;Signal Transduction/*physiology;Cell Movement/*physiology;Support, Non-U.S. Gov't;Astrocytes/physiology;G;Cell Adhesion Molecules, Neuron-Glia/*physiology}, Number = {4}, Organization = {Center for Cellular and Molecular Neurobiology, University of Liege, Liege, Belgium.}, Pages = {357-63.}, Title = {Radial glia phenotype: origin, regulation, and transdifferentiation}, Uuid = {9F6E2B37-DC23-4D53-8D92-0CF33C1E4C56}, Volume = {61}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10931521}} @article{Chandrasekaran:2005, Abstract = {Although it is widely accepted that molecular mechanisms play an important role in the initial establishment of retinotopic maps, it has also long been argued that activity-dependent factors act in concert with molecular mechanisms to refine topographic maps. Evidence of a role for retinal activity in retinotopic map refinement in mammals is limited, and nothing is known about the effect of spontaneous retinal activity on the development of receptive fields in the superior colliculus. Using anatomical and physiological methods with two genetically manipulated mouse models and pharmacological interventions in wild-type mice, we show that spontaneous retinal waves instruct retinotopic map refinement in the superior colliculus of the mouse. Activity-dependent mechanisms may play a preferential role in the mapping of the nasal-temporal axis of the retina onto the colliculus, because refinement is particularly impaired along this axis in mutants without retinal waves. Interfering with both axon guidance cues and activity-dependent cues in the same animal has a dramatic cumulative effect. These experiments demonstrate how axon guidance cues and activity-dependent factors combine to instruct retinotopic map development.}, Author = {Chandrasekaran, Anand R. and Plas, Daniel T. and Gonzalez, Ernesto and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Retinal Ganglion Cells;Retina;Animals;Bicyclo Compounds, Heterocyclic;Mice, Mutant Strains;Phenotype;Superior Colliculi;Visual Pathways;Axons;Nicotinic Agonists;Mice, Inbred C57BL;research support, non-u.s. gov't;Visual Fields;Pyridines;research support, u.s. gov't, p.h.s.;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Receptors, Nicotinic;Brain Mapping; 21 Activity-development; 21 Neurophysiology; currOpinRvw}, Month = {7}, Nlm_Id = {8102140}, Number = {29}, Organization = {Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.}, Pages = {6929-38}, Pii = {25/29/6929}, Pubmed = {16033903}, Title = {Evidence for an instructive role of retinal activity in retinotopic map refinement in the superior colliculus of the mouse}, Uuid = {105BFB51-D724-4C76-A051-CB959A9BACF2}, Volume = {25}, Year = {2005}, url = {papers/Chandrasekaran_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1470-05.2005}} @article{Chandrasekaran:2007, Abstract = {Spontaneous retinal waves during development are thought to provide an instructive signal for precise retinotopic mapping by correlating the activity of neighboring retinal ganglion cells. In mutant mice (beta2-/-) that lack correlated waves, retinocollicular map refinement is impaired. In vivo recordings reveal that neurons in the superior colliculus of beta2-/- mice have large receptive fields and low peak visual responses, resulting in a conservation of total integrated response. We find that this "response homeostasis" is maintained on a cell-by-cell basis, and argue that it does not depend on regulation from the visual cortex during adulthood. Instead, in vitro recordings show that homeostasis arises from the conservation of total synaptic input from the retina, and that it is maintained via different mechanisms over development. In the absence of correlated retinal waves, beta2-/- neurons sample a larger number of weaker retinal inputs relative to controls after the first postnatal week. Once retinal waves are restored, developmental learning rules and homeostasis drive refinement so that fewer, stronger synapses are retained, as in wild-type mice, but from a larger retinal area. Homeostasis in neurons has been shown previously to regulate the gain of synaptic transmission in response to perturbations of activity. Our results suggest that during the development of sensory maps, a unique consequence of homeostatic mechanisms is the precise shaping of neuronal receptive fields in conjunction with activity-dependent competition.}, Author = {Chandrasekaran, Anand R. and Shah, Ruchir D. and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 20:02:17 +0000}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Retina;Animals;Synapses;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Superior Colliculi;Visual Pathways;Models, Biological;Excitatory Amino Acid Agonists;Homeostasis;Mice, Inbred C57BL;Animals, Newborn;N-Methylaspartate;Mice, Knockout;Neurons;Membrane Potentials;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Visual Cortex;Receptors, Nicotinic;Brain Mapping; 21 Activity-development; currOpinRvw}, Month = {2}, Nlm_Id = {8102140}, Number = {7}, Organization = {Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.}, Pages = {1746-55}, Pii = {27/7/1746}, Pubmed = {17301182}, Title = {Developmental homeostasis of mouse retinocollicular synapses}, Uuid = {61BC485C-E54A-4A8B-A820-B9798DC318B8}, Volume = {27}, Year = {2007}, url = {papers/Chandrasekaran_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4383-06.2007}} @article{Chang:2000, Abstract = {Cerebral inflammation often originates in a region where neuronal death occurs and thereafter slowly spreads outward. This study aimed to elucidate the roles of neurons in modulating the production of inflammatory factors stimulated by the bacterial endotoxin lipopolysaccharide (LPS). Culturing neurons with mixed glia reduced nitrite and tumor necrosis factor-alpha (TNF-alpha) production compared to cultures with only mixed glia, and shifted the dose-response curve to the right. The decreased nitrite and TNF-alpha production were not due to the cytotoxicity of LPS. Immunocytochemical analysis of glia-neuron co-cultures revealed the morphological changes in the activated microglia. Culturing PC12 cells with rat mixed-glia also reduced nitrite production. The influence of neurons on glial inflammation was partly due to the cell-cell contacts between neurons and glia via neural cell adhesion molecules (NCAM) because NCAM significantly reduced LPS-stimulated nitrite production. These results demonstrate that neurons reduce the production of inflammatory factors by glia. Since cerebral inflammation is important in many neurological disorders, this study might provide insight about the role of glia-neuron interactions in inflammatory responses in the brain.}, Author = {Chang, R. C. and Hudson, P. and Wilson, B. and Haddon, L. and Hong, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Dose-Response Relationship, Drug;Tumor Necrosis Factor;Animals;Cells, Cultured;Rats;Lipopolysaccharides;Cell Communication;Nitric-Oxide Synthase;L-Lactate Dehydrogenase;11 Glia;PC12 Cells;Rats, Inbred F344;Animals, Newborn;Coculture;Cell Size;Neurons;Neuroglia;Down-Regulation;Mice;Inflammation;Nitric Oxide;Neural Cell Adhesion Molecules}, Medline = {20108612}, Month = {1}, Nlm_Id = {0045503}, Number = {2}, Organization = {Neuropharmacology Section, MD F1-01, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA.}, Pages = {236-44}, Pii = {S0006899399022556}, Pubmed = {10640621}, Title = {Influence of neurons on lipopolysaccharide-stimulated production of nitric oxide and tumor necrosis factor-alpha by cultured glia}, Uuid = {6FF741D3-0ED0-4F06-B988-CDA6AE2E7927}, Volume = {853}, Year = {2000}} @article{Chang:2001, Abstract = {The microenvironment of the CNS has been considered to tonically inhibit glial activities. It has been shown that glia become activated where neuronal death occurs in the aging brain. We have previously demonstrated that neurons tonically inhibit glial activities including their responses to the bacterial endotoxin lipopolysaccharide (LPS). It is not clear whether activation of glia, especially microglia in the aging brain, is the consequence of disinhibition due to neuronal death. This study was designed to determine if glia regain their responsiveness to LPS once the neurons have died in aged cultures. When cultured alone, glia from postnatal day one rat mesencephalons stimulated with LPS (0.1-1000 ng/mL) produced both nitric oxide (NO) and tumor necrosis factor alpha (TNFalpha), yielding a sigmoid and a bell-shaped curve, respectively. When neuron-containing cultures were prepared from embryonic day 14/15 mesencephalons, the shape of the dose-response curve for NO was monotonic and the bell-shaped curve for TNFalpha production was shifted to the right. After 1 month of culture under conditions where neurons die, the production curves for NO and TNFalpha in LPS-stimulated glia shifted back to the left compared to mixed neuron-glia cultures. Immunostaining of rat microglia for the marker CR3 (the receptor for complement component C3) demonstrated that high concentrations of LPS (1 microg/mL) reduced the number of microglia in mixed-glial cultures. In contrast, reduction of CR3 immunostaining was not observed in LPS-stimulated mixed neuron-glia cultures. Taken together, the results demonstrate that disinhibition of the glial response to LPS occurs after neurons die in aged cultures. Once neurons have died, the responsiveness of glia to LPS is restored. Neurons prevented injury to microglia by reducing their responsiveness to LPS. This study broadens our understanding of the ways in which the CNS microenvironment affects cerebral inflammation.}, Author = {Chang, R. C. and Chen, W. and Hudson, P. and Wilson, B. and Han, D. S. and Hong, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Cell Survival;Dose-Response Relationship, Drug;Tumor Necrosis Factor;Animals;Cells, Cultured;Rats;Microglia;Lipopolysaccharides;Cell Count;11 Glia;Time Factors;Rats, Inbred F344;Membrane Glycoproteins;Coculture;Neuroglia;Mesencephalon;Neurons;Nitric Oxide}, Medline = {21103903}, Month = {2}, Nlm_Id = {2985190R}, Number = {4}, Organization = {Neuropharmacology section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, National Institutes of Health, North Carolina, USA. rccchang\@hkucc.hku.hk}, Pages = {1042-9}, Pubmed = {11181823}, Title = {Neurons reduce glial responses to lipopolysaccharide (LPS) and prevent injury of microglial cells from over-activation by LPS}, Uuid = {E040697E-CEC9-4B02-AE9E-81BE0BC1FDD6}, Volume = {76}, Year = {2001}, url = {papers/Chang_JNeurochem2001.pdf}} @article{Chang:2000a, Abstract = {Injection of biocytin provides an effective method for labeling axonal projections. Several difficulties arise when this technique is employed in fetal or early postnatal animals in vivo, including limited access to injection sites and extended post-injection survival periods. To circumvent these problems, we adapted the technique of extracellular biocytin injection for use in explanted brain hemispheres of developing mice. Briefly, entire brain hemispheres from perinatal mice (E16-P9) were removed and placed in oxygenated aCSF in a brain slice recording chamber. Following visually guided injection of biocytin (2\%) into the prelimbic cortex, the brains were then incubated in oxygenated artificial cerebrospinal fluid (aCSF) for varying periods of time and then immersion-fixed in 4\%paraformaldehyde and 0.5\%glutaraldehyde. The next day, the brains were sectioned and processed for biocytin histochemistry using the avidin-biotin-complex method. We examined the method of injection, electrode type, time of injection, and post- injection incubation period. We found that in E16-P9 animals iontophoresis of biocytin using 8- to 12-megaohm patch clamp electrodes for a duration of 10 min provides optimal axonal labeling. Post- injection incubation times of four or more hours are sufficient for labeling fine caliber collaterals as well as axon bundles that reach distances over 3 mm. In vitro injection of biocytin into explanted brain hemispheres provides a quick and easy method for tract tracing in developing brains.}, Author = {Chang, S. L. and LoTurco, J. J. and Nisenbaum, L. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci Methods}, Keywords = {Microelectrodes;10 Development;Limbic System/anatomy &histology/enzymology/growth &development;Cerebral Cortex/anatomy &histology/enzymology/growth &development;Immunohistochemistry;Brain/enzymology/*growth &development;Animals, Newborn/*physiology;Animal;F;Axons/enzymology;Injections;Lysine/administration &dosage/*analogs &derivatives;Mice;Tyrosine 3-Monooxygenase/metabolism;Neural Pathways/anatomy &histology/enzymology/growth &development}, Number = {1}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, 3107 Horsebarn Hill Rd., U-156, Storrs, CT 06269, USA.}, Pages = {1-6.}, Title = {In vitro biocytin injection into perinatal mouse brain: a method for tract tracing in developing tissue}, Uuid = {3B841E04-1C9A-49BE-B9A0-BCDACCA3978E}, Volume = {97}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10771069}} @article{Chang:2008, Abstract = {Phenotypic cell-to-cell variability within clonal populations may be a manifestation of 'gene expression noise', or it may reflect stable phenotypic variants. Such 'non-genetic cell individuality' can arise from the slow fluctuations of protein levels in mammalian cells. These fluctuations produce persistent cell individuality, thereby rendering a clonal population heterogeneous. However, it remains unknown whether this heterogeneity may account for the stochasticity of cell fate decisions in stem cells. Here we show that in clonal populations of mouse haematopoietic progenitor cells, spontaneous 'outlier' cells with either extremely high or low expression levels of the stem cell marker Sca-1 (also known as Ly6a; ref. 9) reconstitute the parental distribution of Sca-1 but do so only after more than one week. This slow relaxation is described by a gaussian mixture model that incorporates noise-driven transitions between discrete subpopulations, suggesting hidden multi-stability within one cell type. Despite clonality, the Sca-1 outliers had distinct transcriptomes. Although their unique gene expression profiles eventually reverted to that of the median cells, revealing an attractor state, they lasted long enough to confer a greatly different proclivity for choosing either the erythroid or the myeloid lineage. Preference in lineage choice was associated with increased expression of lineage-specific transcription factors, such as a >200-fold increase in Gata1 (ref. 10) among the erythroid-prone cells, or a >15-fold increased PU.1 (Sfpi1) (ref. 11) expression among myeloid-prone cells. Thus, clonal heterogeneity of gene expression level is not due to independent noise in the expression of individual genes, but reflects metastable states of a slowly fluctuating transcriptome that is distinct in individual cells and may govern the reversible, stochastic priming of multipotent progenitor cells in cell fate decision.}, Author = {Chang, Hannah H. and Hemberg, Martin and Barahona, Mauricio and Ingber, Donald E. and Huang, Sui}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Transcription, Genetic;Cell Differentiation;Animals;Trans-Activators;GATA1 Transcription Factor;Antigens, Ly;Myeloid Cells;research support, non-u.s. gov't;Gene Expression Profiling;Cell Line;Erythroid Cells;Cell Lineage;research support, n.i.h., extramural;Hematopoietic Stem Cells;Mice;Proto-Oncogene Proteins;Membrane Proteins;24 Pubmed search results 2008;Clone Cells;research support, u.s. gov't, non-p.h.s.;Stochastic Processes}, Month = {5}, Nlm_Id = {0410462}, Number = {7194}, Organization = {Vascular Biology Programme, Department of Pathology and Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {544-7}, Pii = {nature06965}, Pubmed = {18497826}, Title = {Transcriptome-wide noise controls lineage choice in mammalian progenitor cells}, Uuid = {0E2B7A0C-09AC-498D-ABF3-CF4A2E10D507}, Volume = {453}, Year = {2008}, url = {papers/Chang_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06965}} @article{Chang:2005, Abstract = {OBJECTIVE: To define the behavioral profile of periventricular nodular heterotopia (PNH), a malformation of cortical development that is associated with seizures but reportedly normal intelligence, and to correlate the results with anatomic and clinical features of this disorder. METHODS: Ten consecutive subjects with PNH, all with epilepsy and at least two periventricular nodules, were studied with structural MRI and neuropsychological testing. Behavioral results were statistically analyzed for correlation with other features of PNH. RESULTS: Eight of 10 subjects had deficits in reading skills despite normal intelligence. Processing speed and executive function were also impaired in some subjects. More marked reading difficulties were seen in subjects with more widely distributed heterotopia. There was no correlation between reading skills and epilepsy severity or antiepileptic medication use. CONCLUSION: The neuronal migration disorder of periventricular nodular heterotopia is associated with an impairment in reading skills despite the presence of normal intelligence.}, Author = {Chang, B. S. and Ly, J. and Appignani, B. and Bodell, A. and Apse, K. A. and Ravenscroft, R. S. and Sheen, V. L. and Doherty, M. J. and Hackney, D. B. and O'Connor, M. and Galaburda, A. M. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1526-632X}, Journal = {Neurology}, Keywords = {Neuropsychological Tests;Research Support, Non-U.S. Gov't;Magnetic Resonance Imaging;Humans;Middle Aged;21 Epilepsy;Female;Epilepsy;Predictive Value of Tests;Cell Movement;Dyslexia;Male;Intelligence;Research Support, U.S. Gov't, P.H.S.;Nervous System Malformations;Cerebral Cortex;Neurons;21 Neurophysiology;Adult;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Choristoma;Adolescent}, Month = {3}, Nlm_Id = {0401060}, Number = {5}, Organization = {Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA. bchang\@bidmc.harvard.edu}, Pages = {799-803}, Pii = {64/5/799}, Pubmed = {15753412}, Title = {Reading impairment in the neuronal migration disorder of periventricular nodular heterotopia}, Uuid = {396B8700-7587-4BEE-8EF0-47A5E7E0E31F}, Volume = {64}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1212/01.WNL.0000152874.57180.AF}} @article{Chang:2006, Abstract = {Mutations in the MECP2 gene cause Rett syndrome (RTT). Bdnf is a MeCP2 target gene; however, its role in RTT pathogenesis is unknown. We examined Bdnf conditional mutant mice for RTT-relevant pathologies and observed that loss of BDNF caused smaller brain size, smaller CA2 neurons, smaller glomerulus size, and a characteristic hindlimb-clasping phenotype. BDNF protein level was reduced in Mecp2 mutant mice, and deletion of Bdnf in Mecp2 mutants caused an earlier onset of RTT-like symptoms. To assess whether this interaction was functional and potentially therapeutically relevant, we increased BDNF expression in the Mecp2 mutant brain with a conditional Bdnf transgene. BDNF overexpression extended the lifespan, rescued a locomotor defect, and reversed an electrophysiological deficit observed in Mecp2 mutants. Our results provide in vivo evidence for a functional interaction between Mecp2 and Bdnf and demonstrate the physiological significance of altered BDNF expression/signaling in RTT disease progression.}, Author = {Chang, Qiang and Khare, Gargi and Dani, Vardhan and Nelson, Sacha and Jaenisch, Rudolf}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't ;Methyl-CpG-Binding Protein 2;Disease Models, Animal;24 Pubmed search results 2008;Immunohistochemistry;Male;Animals;Brain;comparative study ;Rett Syndrome;Electric Stimulation;RNA, Messenger;research support, n.i.h., extramural ;Motor Activity;Disease Progression;Behavior, Animal;Brain-Derived Neurotrophic Factor;Mutation;Gene Expression Regulation;Organ Size;Action Potentials;Patch-Clamp Techniques;Female;Enzyme-Linked Immunosorbent Assay;Animals, Newborn;Mice, Knockout;21 Neurophysiology;Mice;Neurons;Humans;in vitro ;Reverse Transcriptase Polymerase Chain Reaction}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.}, Pages = {341-8}, Pii = {S0896-6273(06)00010-9}, Pubmed = {16446138}, Title = {The disease progression of Mecp2 mutant mice is affected by the level of BDNF expression}, Uuid = {6853FBC3-7D8A-46E7-9960-4036757111F7}, Volume = {49}, Year = {2006}, url = {papers/Chang_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.12.027}} @article{Chao:2007, Abstract = {MeCP2 is a transcriptional repressor critical for normal neurological function. Prior studies demonstrated that either loss or doubling of MeCP2 results in postnatal neurodevelopmental disorders. To understand the impact of MeCP2 expression on neuronal function, we studied the synaptic properties of individual neurons from mice that either lack or express twice the normal levels of MeCP2. Hippocampal glutamatergic neurons that lack MeCP2 display a 46\%reduction in synaptic response, whereas neurons with doubling of MeCP2 exhibit a 2-fold enhancement in synaptic response. Further analysis shows that these changes were primarily due to the number of synapses formed. These results reveal that MeCP2 is a key rate-limiting factor in regulating glutamatergic synapse formation in early postnatal development and that changes in excitatory synaptic strength may underlie global network alterations in neurological disorders due to altered MeCP2 levels.}, Author = {Chao, Hsiao-Tuan T. and Zoghbi, Huda Y. and Rosenmund, Christian}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.}, Pages = {58-65}, Pii = {S0896-6273(07)00647-2}, Pubmed = {17920015}, Title = {MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number}, Uuid = {CE053998-14BC-4E10-A1FB-D81D0E212059}, Volume = {56}, Year = {2007}, url = {papers/Chao_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.08.018}} @article{Chapman:1989, Abstract = {A unilateral occipital excision was performed on 14 fetal lambs at about the 70th day of gestation, and the brains were examined postnatally for gross morphological and histologic changes. Three operated brains revealed a posterior shift of the principal transverse sulcus in the ipsilateral hemisphere. This sulcus is remote from the area of excision, which was usually represented by a cystic cavity. Histologic examination showed that the dorsal lateral geniculate body was reduced in size in all but three of the operated brains. In two brains with the changed gyral pattern there was also a reduction in the size of the white fiber tracts of the frontal lobe. No evidence of neural regeneration was found in any of the brains. The implications of these findings from the point of view of possible neurosurgical intervention in the fetus are considered.}, Author = {Chapman, S. A. and Bannister, C. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0090-3019}, Journal = {Surg Neurol}, Keywords = {Fetus;Research Support, Non-U.S. Gov't;Occipital Lobe;Sheep;Animals;Brain;24 Pubmed search results 2008;Frontal Lobe}, Medline = {89317809}, Month = {8}, Nlm_Id = {0367070}, Number = {2}, Organization = {Department of Pathology, Medical School, University of Manchester, England.}, Pages = {98-104}, Pubmed = {2749462}, Title = {Effect of excision of occipital lobe tissue on about the 70th day of gestation on the growth and development of the sheep's brain}, Uuid = {5A9664D0-9EEF-4435-ABD8-F51D06B0DF13}, Volume = {32}, Year = {1989}} @article{Charlton:2000, Abstract = {Considerable evidence points to an involvement of neural cell adhesion molecule (NCAM) in myoblast fusion. Changes in the level of NCAM expression, isoform specificity, and localization in muscle cells and tissues correspond to key morphogenetic events during muscle differentiation and repair. Furthermore, anti-NCAM antibodies have been shown by others to reduce the rate of myoblast fusion, whereas overexpression of NCAM cDNAs increases the rate of myoblast fusion compared to controls. In this study we have used a novel fusion assay based on intracistronic complementation of lacZ, in combination with fluorescent X-gal histochemistry and immunocytochemistry to assess levels of NCAM expression in individual muscle cells. Our results indicate that a substantial proportion of newly fused myoblasts have NCAM expression levels unchanged from the levels of the surrounding unfused population suggesting that increased expression of NCAM is not required for wild-type myoblasts to fuse. Moreover, pure populations of primary myoblasts isolated from mice homozygous null for NCAM and therefore lacking the molecule, when placed in differentiation medium, consistently fused to form contractile myotubes with kinetics equivalent to wild-type primary myoblasts. We conclude that the increase in expression of NCAM, although typically observed during myogenesis, is not essential to myoblast fusion to form myotubes.}, Author = {Charlton, C. A. and Mohler, W. A. and Blau, H. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {Transfection;Gene Expression Regulation, Developmental;Neural Cell Adhesion Molecules;Cell Adhesion;Research Support, Non-U.S. Gov't;Cell Differentiation;Kinetics;Muscles;Mice, Knockout;Cell Fusion;Research Support, U.S. Gov't, P.H.S.;Microscopy, Fluorescence;Animals;Cells, Cultured;Mice;Genes, Reporter;24 Pubmed search results 2008}, Medline = {20237581}, Month = {5}, Nlm_Id = {0372762}, Number = {1}, Organization = {Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, California 94305, USA.}, Pages = {112-9}, Pii = {S0012-1606(00)99654-4}, Pubmed = {10772795}, Title = {Neural cell adhesion molecule (NCAM) and myoblast fusion}, Uuid = {9AD35254-3357-40B1-B7A2-EA463B1B955A}, Volume = {221}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/dbio.2000.9654}} @article{Chatt:1984, Abstract = {Clinically, phenytoin is thought to be useful in controlling seizure activity by preventing it's spread from the focus to neighboring tissue. Experimentally, it has been suggested that phenytoin's principal action is no longer polysynaptic pathways with primary foci affected less than surrounding tissue. In this study, we present data confirming these basic experimental conclusions in foci induced in striate neocortical layer 4 of the cat. By using discrete penicillin microinjections strategically placed into this most penicillin-sensitive neocortical layer and recording simultaneously from several layers, we have been able to expand upon these conclusions by identifying this differential action at the interlaminar level. Epileptiform activity recorded from superficial laminae bordering layer 4, and into which layer 4's primary projections terminate, is suppressed preferentially by phenytoin. These superficial layers are also those that project into neighboring areas of the cat visual cortex. It would appear, then, that phenytoin begins protecting the cortex from seizure spread at the first synaptic termination into which this layer 4 primary focus projects. A discussion of the basic mechanisms of action that may be responsible for these results is also presented.}, Author = {Chatt, A. B. and Ebersole, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Epilepsy;Penicillins;Electroencephalography;Research Support, Non-U.S. Gov't;Phenytoin;21 Neurophysiology;Cats;Research Support, U.S. Gov't, P.H.S.;Research Support, U.S. Gov't, Non-P.H.S.;Animals;Cerebral Cortex;24 Pubmed search results 2008;21 Epilepsy}, Medline = {84179911}, Month = {3}, Nlm_Id = {0045503}, Number = {2}, Pages = {394-400}, Pubmed = {6713200}, Title = {Phenytoin preferentially suppresses epileptiform activity in the superficial cortical layers of the cat}, Uuid = {DA74EF9E-EBBA-4B46-B9B5-006B55BB9573}, Volume = {295}, Year = {1984}} @article{Chatt:1988, Abstract = {Simultaneous recordings from three laminae within the cat visual cortex following differential intralaminar injections of strychnine (i) confirmed that low strychnine concentrations (5 mM) induce interictal-like epileptiform abnormalities (late responses) only when injected into superficial layers 2 and 3, (ii) revealed that these abnormalities are generated locally within these layers, and (iii) showed that they remain local phenomena by not spreading vertically into other cortical layers. Higher strychnine concentrations (20 mM), however, (iv) obscured these laminar differences by increasing layer 4 sensitivity to this agent in addition to the maximally sensitive superficial layers, and further (v) revealed nonlocal, vertically propagating, interictal-like abnormalities (late responses) following layer 4 injections which are preceded by an increase in thalamocortically mediated activity within this layer (enhanced physiologic responses). When penicillin was used as the convulsant, propagated interictal-like responses (late responses) induced in any layer were always preceded by a thalamocortically mediated response from layer 4 (enhanced physiologic responses); a condition clearly unlike the 5 mM but similar to the 20 mM strychnine foci observed in this study. These results suggest that convulsant action upon the thalamocortical circuitry of layer 4 is essential for the development of propagating as opposed to local epileptiform activity. Further, these results may also help explain why some cortical seizure disorders remain localized (focal) whereas others secondarily generalize to distal brain sites (i.e., complex partial seizures of extratemporal origin).}, Author = {Chatt, A. B. and Ebersole, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Epilepsy;Penicillins;Research Support, Non-U.S. Gov't;21 Neurophysiology;Cats;Comparative Study;Research Support, U.S. Gov't, P.H.S.;Strychnine;Research Support, U.S. Gov't, Non-P.H.S.;Electrophysiology;Thalamus;Animals;Cerebral Cortex;24 Pubmed search results 2008;21 Epilepsy}, Medline = {88196274}, Month = {5}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Neurology, Yale University School of Medicine, New Haven, Connecticut 06510.}, Pages = {365-80}, Pubmed = {3360075}, Title = {Comparisons between strychnine and penicillin epileptogenesis suggest that propagating epileptiform abnormalities require the potentiation of thalamocortical circuitry in neocortical layer 4}, Uuid = {DB6837F1-7BBE-4F34-B4F8-05A297DCB89B}, Volume = {100}, Year = {1988}} @article{Chattopadhyaya:2007, Abstract = {The development of GABAergic inhibitory circuits is shaped by neural activity, but the underlying mechanisms are unclear. Here, we demonstrate a novel function of GABA in regulating GABAergic innervation in the adolescent brain, when GABA is mainly known as an inhibitory transmitter. Conditional knockdown of the rate-limiting synthetic enzyme GAD67 in basket interneurons in adolescent visual cortex resulted in cell autonomous deficits in axon branching, perisomatic synapse formation around pyramidal neurons, and complexity of the innervation fields; the same manipulation had little influence on the subsequent maintenance of perisomatic synapses. These effects of GABA deficiency were rescued by suppressing GABA reuptake and by GABA receptor agonists. Germline knockdown of GAD67 but not GAD65 showed similar deficits, suggesting a specific role of GAD67 in the maturation of perisomatic innervation. Since intracellular GABA levels are modulated by neuronal activity, our results implicate GAD67-mediated GABA synthesis in activity-dependent regulation of inhibitory innervation patterns.}, Author = {Chattopadhyaya, Bidisha and Di Cristo, Graziella and Wu, Cai Zhi and Knott, Graham and Kuhlman, Sandra and Fu, Yu and Palmiter, Richard D. and Huang, Z. Josh}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {gamma-Aminobutyric Acid;Signal Transduction;Animals;Synapses;Transfection;Phosphopyruvate Hydratase;Visual Pathways;Axons;Mice, Transgenic;Green Fluorescent Proteins;research support, non-u.s. gov't;Time Factors;Organ Culture Techniques;Glutamate Decarboxylase;21 Neurophysiology;Parvalbumins;Neurons;21 Activity-development;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Isoenzymes;Neural Inhibition;Visual Cortex;in vitro}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.}, Pages = {889-903}, Pii = {S0896-6273(07)00372-8}, Pubmed = {17582330}, Title = {GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex}, Uuid = {16A706C8-471D-4B25-8044-D423714A45ED}, Volume = {54}, Year = {2007}, url = {papers/Chattopadhyaya_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.05.015}} @article{Chavez:2002, Abstract = {Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that regulates the adaptive response to hypoxia in mammalian cells. It consists of a regulatory subunit HIF-1alpha, which accumulates under hypoxic conditions, and a constitutively expressed subunit HIF-1beta. In this study we analyzed HIF-1alpha expression in the rat cerebral cortex after transient global ischemia induced by cardiac arrest and resuscitation. Our results showed that HIF-1alpha accumulates as early as 1 hr of recovery and persists for at least 7 d. In addition, the expression of HIF-1 target genes, erythropoietin and Glut-1, were induced at 12 hr to 7d of recovery. A logical explanation for HIF-1alpha accumulation might be that the brain remained hypoxic for prolonged periods after resuscitation. By using the hypoxic marker 2-(2-nitroimidazole-1[H]-y1)-N-(2,2,3,3,3-pentafluoropropyl)-acetamide (EF5), we showed that the brain is hypoxic during the first hours of recovery from cardiac arrest, but the tissue is no longer hypoxic at 2 d. Thus, the initial ischemic episode must have activated other nonhypoxic mechanisms that maintain prolonged HIF-1alpha accumulation. One such mechanism might be initiated by insulin-like growth factor-1 (IGF-1). Our results showed that IGF-1 expression was upregulated after cardiac arrest and resuscitation. In addition, we showed that IGF-1 was able to induce HIF-1alpha in pheochromocytoma cells and cultured neurons as well as in the brain of rats that received intracerebroventricular and systemic IGF-1 infusion. Moreover, infusion of a selective IGF-1 receptor antagonist abrogates HIF-1alpha accumulation after cardiac arrest and resuscitation. Our study suggest that activation of HIF-1 might be part of the mechanism by which IGF-1 promotes cell survival after cerebral ischemia. 1529-2401 Journal Article}, Author = {Chavez, J. C. and LaManna, J. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:43 -0400}, Journal = {J Neurosci}, Keywords = {Receptor, IGF Type 1/antagonists &inhibitors/biosynthesis;Animals;Insulin-Like Growth Factor I/*metabolism/pharmacology;Hydrocarbons, Fluorinated;Rats;Up-Regulation;Neurons/drug effects/metabolism;Nuclear Proteins/genetics/*metabolism;Etanidazole/*analogs &derivatives;Rats, Wistar;*Ubiquitin-Protein Ligases;Male;*Tumor Suppressor Proteins;Disease Models, Animal;PC12 Cells;DNA-Binding Proteins/genetics/*metabolism;Cardiopulmonary Resuscitation;Ligases/metabolism;Cerebral Cortex/cytology/drug effects/*metabolism;Heart Arrest, Induced;Support, U.S. Gov't, P.H.S.;04 Adult neurogenesis factors;Peptide Hydrolases/metabolism;Immunohistochemistry;C pdf;Hypoxia, Brain/metabolism;Ischemic Attack, Transient/*metabolism}, Number = {20}, Organization = {Department of Anatomy, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4938, USA.}, Pages = {8922-31}, Title = {Activation of hypoxia-inducible factor-1 in the rat cerebral cortex after transient global ischemia: potential role of insulin-like growth factor-1}, Uuid = {D94490D2-8822-4D78-9657-C40647686904}, Volume = {22}, Year = {2002}, url = {papers/Chavez_JNeurosci2002.pdf}} @article{Chazal:2000, Abstract = {In vertebrates, interneurons of the olfactory bulb (OB) are generated postnatally and throughout life at the subventricular zone of the forebrain. The neuronal precursors migrate tangentially through the forebrain using a well defined pathway, the rostral migratory stream (RMS), and a particular mode of migration in a chain-like organization. A severe size reduction of the OB represents the most striking morphological phenotype in neural cell adhesion molecule (NCAM)- deficient mice. This defect has been traced back to a migration deficit of the precursors in the RMS and linked to the lack of the polysialylated form of NCAM. In this study we investigate the morphological alterations and functional properties of the RMS in mice totally devoid of all isoforms of NCAM and polysialic acid (PSA). We show that a morphologically altered, but defined and continuous pathway exists in mutants, and we present in vivo and in vitro evidence that PSA-NCAM in the RMS is not essential for the formation and migration of chains. Instead, we find a massive gliosis associated with the formation of membrane specializations in a heterotypic manner, linking precursors to astrocytes. This finding and the over-representation and defasciculation of axons in the pathway suggest that important interactions between migrating cells and their stationary environment are perturbed in the mutants. Finally, we used transplantation experiments to demonstrate that lack of PSA-NCAM leads to a decrease but not a total blockade of migration and demonstrate that the mutant RMS is functional in transporting normal neuronal precursors to the OB.}, Author = {Chazal, G. and Durbec, P. and Jankovski, A. and Rougon, G. and Cremer, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {J Neurosci}, Keywords = {Cell Movement/*physiology;Stem Cells/physiology;Olfactory Bulb/abnormalities/*physiology/ultrastructure;Animal;Neurons/cytology/*physiology/ultrastructure;Mice, Inbred C57BL;Sialic Acids/genetics;Axons/physiology/ultrastructure;Crosses, Genetic;Neuroglia/cytology/physiology/ultrastructure;Neural Cell Adhesion Molecules/chemistry/genetics/*physiology;Support, Non-U.S. Gov't;Cerebral Ventricles/cytology/physiology;Mice, Knockout;Olfactory Pathways/cytology/physiology;04 Adult neurogenesis factors;Mice;Prosencephalon/cytology/*physiology/ultrastructure;C pdf;Protein Isoforms/deficiency/genetics/physiology;Organ Culture}, Number = {4}, Organization = {Laboratoire de Genetique et Physiologie du Developpement, Institut de Biologie du Developpement de Marseille, Centre National de la Recherche Scientifique/ Universite de la Sante et de la Recherche Medicale, INSERM, Paris Cedex, France.}, Pages = {1446-57.}, Title = {Consequences of neural cell adhesion molecule deficiency on cell migration in the rostral migratory stream of the mouse}, Uuid = {32A22AA6-9886-45E0-A8D8-82C41C0B6E64}, Volume = {20}, Year = {2000}, url = {papers/Chazal_JNeurosci2000.pdf}} @article{Chen:2006a, Abstract = {Alternative splicing of Dscam generates an enormous molecular diversity with maximally 38,016 different receptors. Whether this large diversity is required in vivo is currently unclear. We examined the role of Dscam in neuron-target recognition of single mechanosensory neurons, which connect with different target cells through multiple axonal branches. Analysis of Dscam null neurons demonstrated an essential role of Dscam for growth and directed extension of axon branches. Expression of randomly chosen single isoforms could not rescue connectivity but did restore basic axonal extension and rudimentary branching. Moreover, two Dscam alleles were generated that each reduced the maximally possible Dscam diversity to 22,176 isoforms. Reduction of Dscam diversity resulted in specific connectivity defects of mechanosensory neurons. Furthermore, the observed allele-specific phenotypes suggest functional differences among isoforms. Our findings provide evidence that a very large number of structurally unique receptor isoforms is required to ensure fidelity and precision of neuronal connectivity.}, Author = {Chen, Brian E. and Kondo, Masahiro and Garnier, Am{\'e}lie and Watson, Fiona L. and P{\"u}ettmann-Holgado, Roland and Lamar, David R. and Schmucker, Dietmar}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {10 Development;Cell Differentiation;research support, n.i.h., extramural ;Animals;Variation (Genetics);Neural Pathways;Alternative Splicing;Receptors, Cell Surface;Phenotype;Nervous System;Mutation;Neurons, Afferent;Mechanoreceptors;10 circuit formation;research support, non-u.s. gov't ;Protein Structure, Tertiary;Drosophila melanogaster;Genotype;Protein Isoforms;24 Pubmed search results 2008;Growth Cones;Drosophila Proteins}, Month = {5}, Nlm_Id = {0413066}, Number = {3}, Organization = {Department of Cancer Biology, Dana-Farber Cancer Institute, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {607-20}, Pii = {S0092-8674(06)00445-4}, Pubmed = {16678102}, Title = {The molecular diversity of Dscam is functionally required for neuronal wiring specificity in Drosophila}, Uuid = {59E3D3A6-39B7-4CF7-B08E-CCE7CC93BD2B}, Volume = {125}, Year = {2006}, url = {papers/Chen_Cell2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.03.034}} @article{Chen:2000, Abstract = {PURPOSE: Misplaced (heterotopic) cortical neurons are a common feature of developmental epilepsies. To better understand seizure disorders associated with cortical heterotopia, the sites of aberrant discharge activity were investigated in vivo and in vitro in a seizure-prone mutant rat (tish) exhibiting subcortical band heterotopia. METHODS: Depth electrode recordings and postmortem assessment of regional c-fos mRNA levels were used to characterize the distribution of aberrant discharge activity during spontaneous seizures in vivo. Electrophysiologic recordings of spontaneous and evoked activity also were performed by using in vitro brain slices from the tish rat treated with proconvulsant drugs (penicillin and 4-aminopyridine). RESULTS: Depth electrode recordings demonstrate that seizure activity begins almost simultaneously in the normotopic and heterotopic areas of the tish neocortex. Spontaneous seizures induce c-fos mRNA in normotopic and heterotopic neocortical areas, and limbic regions. The threshold concentrations of proconvulsant drugs for inducing epileptiform spiking were similar in the normotopic and heterotopic areas of tish brain slices. Manipulations that blocked communication between the normotopic and heterotopic areas of the cortex inhibited spiking in the heterotopic, but not the normotopic, area of the cortex. CONCLUSIONS: These findings indicate that aberrant discharge activity occurs in normotopic and heterotopic areas of the neocortex, and in certain limbic regions during spontaneous seizures in the tish rat. Normotopic neurons are more prone to exhibit epileptiform activity than are heterotopic neurons in the tish cortex, and heterotopic neurons are recruited into spiking by activity initiated in normotopic neurons. The findings indicate that seizures in the tish brain primarily involve telencephalic structures, and suggest that normotopic neurons are responsible for initiating seizures in the dysplastic neocortex.}, Author = {Chen, Z. F. and Schottler, F. and Bertram, E. and Gall, C. M. and Anzivino, M. J. and Lee, K. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:42 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Electrophysiology;Animals;In Vitro;Evoked Potentials;Rats;Seizures;Brain;21 Epilepsy;Epilepsy;Genes, fos;RNA, Messenger;Tetrodotoxin;Get paper from library;In Situ Hybridization;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;24 Pubmed search results 2008;Autoradiography;Penicillin G;Electrodes, Implanted;Rats, Mutant Strains}, Medline = {20264387}, Month = {5}, Nlm_Id = {2983306R}, Notes = {have print}, Number = {5}, Organization = {Department of Neuroscience, University of Virginia Health Science Center, Charlottesville, Virginia 22908, USA.}, Pages = {493-501}, Pubmed = {10802753}, Title = {Distribution and initiation of seizure activity in a rat brain with subcortical band heterotopia}, Uuid = {B46F43C4-D4ED-4291-89DF-09E8AF188F37}, Volume = {41}, Year = {2000}, url = {papers/Chen_Epilepsia2000.pdf}} @article{Chen:2006, Abstract = {An important issue in stem cell biology relates to mechanisms of cellular plasticity. Specifically, could any observed multipotency of, e.g., adult stem cells arise from true transdifferentiation or as a result of cell-cell fusion? We studied this issue using a culture paradigm of astrocyte monolayers and multipotent neurospheres generated from neonatal cerebellar cortex and the subventricular zone (SVZ). Based on fluorescence in situ hybridization (FISH), cells from these cultures were found to contain an abnormal number of sex chromosomes, suggesting that cellular fusion is a common in vitro occurrence. A Cre/lox recombination method was also exploited to further confirm the evidence of fusion. Next, we assessed the potential of fusogenic microglial involvement by combining CD11b immunolabeling with FISH sex chromosome analysis. Differentiating neurospheres were also studied from the PU.1 knockout mouse that lacks cells of myeloid origin, presumed to be a source of central nervous system microglia. Very few cells immunopositive for the microglial marker CD11b were found to be aneuploid, and there was no difference in fusion frequency between PU.1+/+ and PU.1-/- neurospheres. These results, together, suggest that stem and/or progenitor cells that generate neurons and glia in culture possess the ability to generate fused polyploidal cells, but microglial participation is not a requirement for fusion to occur. In addition to caution that should be exerted during the interpretation of in vitro neural cell plasticity, the data also suggest that novel therapeutic treatments could be designed that exploit cellular fusion in rescue paradigms for degenerating neuronal populations.}, Author = {Chen, and Laywell, and Marshall, and Walton, and Zheng, and Steindler,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {03 Adult neurogenesis progenitor source;08 Aberrant cell cycle;11 Glia;22 Stem cells;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0370712}, Organization = {Department of Neuroscience, The McKnight Brain Institute of the University of Florida, PO Box 100244, Gainesville, FL 32610, USA.}, Pii = {S0014-4886(05)00421-8}, Pubmed = {16406350}, Title = {Fusion of neural stem cells in culture}, Uuid = {B751DF09-7CD8-4F49-B996-3AC5A6132D5E}, Year = {2006}, url = {papers/Chen_ExpNeurol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2005.11.016}} @article{Chen:2000a, Abstract = {Increasing evidence suggests that mood disorders are associated with a reduction in regional CNS volume and neuronal and glial cell atrophy or loss. Lithium, a mainstay in the treatment of mood disorders, has recently been demonstrated to robustly increase the levels of the cytoprotective B-cell lymphoma protein-2 (bcl-2) in areas of rodent brain and in cultured cells. In view of bcl-2's antiapoptotic and neurotrophic effects, the present study was undertaken to determine if lithium affects neurogenesis in the adult rodent hippocampus. Mice were chronically treated with lithium, and 5-bromo-2-deoxyuridine (BrdU) labeling of dividing cells was conducted over 12 days. Immunohistochemical analysis was undertaken 1 day after the last injection, and three-dimensional stereological cell counting revealed that lithium produced a significant 25\%increase in the BrdU-labeled cells in the dentate gyrus. Double-labeling immunofluorescence studies were undertaken to co-localize BrdU-positive cells with neuron-specific nuclear protein and showed that approximately 65\%of the cells were double-labeled. These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long-term treatment of other neuropsychiatric disorders.}, Author = {Chen, G. and Rajkowska, G. and Du, F. and Seraji-Bozorgzad, N. and Manji, H. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {J Neurochem}, Keywords = {Proto-Oncogene Proteins c-bcl-2/metabolism;Antigens, Differentiation/metabolism;Phenotype;Lithium/*pharmacology;Animal;Hippocampus/cytology/*drug effects/metabolism;Mice, Inbred C57BL;Nerve Regeneration/drug effects;Male;Neurons/cytology/*drug effects/metabolism;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Mice;Immunohistochemistry;C pdf;Bromodeoxyuridine;Cell Division/drug effects}, Number = {4}, Organization = {Laboratory of Molecular Pathophysiology, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, Michigan 48201, USA. gchen\@med.wayne.edu}, Pages = {1729-34.}, Title = {Enhancement of hippocampal neurogenesis by lithium}, Uuid = {8B65E5FC-0B7D-421D-A472-DDA53AF94D85}, Volume = {75}, Year = {2000}, url = {papers/Chen_JNeurochem2000}} @article{Chen:1999, Abstract = {Qualitative and quantitative changes were found in the cerebellar circuitry of old as compared to young rats. The old group had a reduced number of synapses (at least 30\%), however, there was an increase in the size of remaining synaptic components (13.5\%for spine head volume, 66\%for bouton volume, and 17\%for the area of synaptic contact zones). Furthermore, there were pronounced morphological changes in the older group appearing as: 1) prominent lipofuscin bodies in Purkinje cell somata, 2) numerous myelinated fibers in the lower part of the molecular layer, 3) tortuous Purkinje cell dendrites in a thinned molecular layer, and 4) abundant vacuolar profiles and membrane swirls in small and intermediate-sized dendrites. Our findings suggest that Purkinje cell dendrites are dying-back reducing the target field for granule cells and that remaining synaptic sites compensate by increasing synaptic contact area as well as the size of pre- and postsynaptic structures.}, Author = {Chen, S. and Hillman, D. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Purkinje Cells;Myelin Sheath;Synapses;Animals;Aging;Rats;Neuronal Plasticity;Vacuoles;Female;Axons;Endoplasmic Reticulum;Not relevant;Calcium-Binding Protein, Vitamin D-Dependent;11 Glia;Dendrites;Rats, Inbred F344;Lipofuscin;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Nerve Tissue Proteins}, Medline = {20085219}, Month = {3}, Nlm_Id = {0364620}, Number = {3}, Organization = {Departments of Otolaryngology and Physiology/Biophysics, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA.}, Pages = {187-96}, Pubmed = {10617901}, Title = {Dying-back of Purkinje cell dendrites with synapse loss in aging rats}, Uuid = {4E0D75B6-63B9-4441-9C49-0056C2F7F20B}, Volume = {28}, Year = {1999}, url = {papers/Chen_JNeurocytol1999.pdf}} @article{Chen:2002, Abstract = {Following peripheral nerve transection, CX3CR1 and TGF-beta1 are increased in a time-dependent manner within the injured facial motor nucleus. To explore the relationship between TGF-beta1 and CX3CR1 in the CNS, the effects of TGF-beta1 on CX3CR1 mRNA, protein and fractalkine-dependent stimulation of signal transduction cascades in primary cultures of rat microglia were examined. TGF-beta1 increased steady state levels of CX3CR1 mRNA, 125I-fractalkine binding sites and blunted fractalkine-stimulated ERK1/2 phosphorylation. The half-life of CX3CR1 mRNA was unaltered by TGF-beta1 and two potential Smad binding elements (SBEs) were identified in the rat CX3CR1 promoter. TGF-beta1 may shift fractalkine-dependent signaling away from activation of ERK1/2 towards other pathways and/or may provide a mechanism for microglia to more strongly adhere to neurons.}, Author = {Chen, Shuzhen and Luo, Defang and Streit, Wolfgang J. and Harrison, Jeffrey K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Dose-Response Relationship, Drug;Signal Transduction;Nerve Degeneration;Animals;Gene Expression Regulation;Up-Regulation;Rats;Transforming Growth Factor beta;Cells, Cultured;Microglia;Rats, Sprague-Dawley;RNA, Messenger;Not relevant;11 Glia;Time Factors;Chemokines, CX3C;Animals, Newborn;Receptors, Interleukin-8A;Support, U.S. Gov't, P.H.S.;Membrane Proteins;Mitogen-Activated Protein Kinases;Transcription, Genetic}, Medline = {22336839}, Month = {12}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, FL 32610-0267, USA.}, Pages = {46-55}, Pii = {S0165572802003545}, Pubmed = {12446007}, Title = {TGF-beta1 upregulates CX3CR1 expression and inhibits fractalkine-stimulated signaling in rat microglia}, Uuid = {CCAE918A-039B-4AA5-BE97-F22835215BF3}, Volume = {133}, Year = {2002}} @article{Chen:2003a, Abstract = {Neuronal heterotopia has a strong association with epilepsy, but the mechanisms that underlie this relationship are largely unknown. We have utilized the in utero irradiated rat model to study circuit abnormalities in experimentally induced subcortical heterotopic gray matter. Spontaneous and miniature inhibitory (IPSCs) and excitatory (EPSCs) postsynaptic currents were recorded from visualized heterotopic pyramidal neurons in in vitro hemispheric slices and compared with control neocortical pyramidal neurons using the whole cell patch-clamp technique. The frequency of spontaneous and miniature IPSCs was significantly reduced in pyramidal neurons from heterotopic cortex. Amplitude and kinetics of IPSCs were not different between the two groups. Spontaneous and miniature EPSCs were not different between the two groups. Short-term synaptic plasticity of stimulus-evoked EPSCs showed depression in heterotopic neurons and facilitation in control pyramidal neurons. This study shows a selective impairment of the GABAergic circuitry in experimental heterotopic gray matter. We have reported similar findings in normotopic dysplastic cortex from this model. Taken together, these studies demonstrate a pervasive defect in inhibition throughout the cortex of irradiated rats with cortical dysplasia and neuronal heterotopia. This may have important implications regarding cortical development and function following in utero injuries.}, Author = {Chen, Huan-Xin X. and Roper, Steven N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:42 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {10 Development;Pregnancy;Animals;Rats;Neuronal Plasticity;Synaptic Transmission;Patch-Clamp Techniques;Female;Epilepsy;Pyramidal Cells;Organ Culture Techniques;Brain Diseases;10 genetics malformation;research support, u.s. gov't, p.h.s.;Cerebral Cortex;24 Pubmed search results 2008;Choristoma;Neural Inhibition;Excitatory Postsynaptic Potentials}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Neurological Surgery, University of Florida, Gainesville 32610, USA.}, Pages = {150-8}, Pubmed = {12522167}, Title = {Reduction of spontaneous inhibitory synaptic activity in experimental heterotopic gray matter}, Uuid = {778E5A90-1ADA-421B-8E3C-12276A53930B}, Volume = {89}, Year = {2003}, url = {papers/Chen_JNeurophysiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00325.2002}} @article{Chen:2001a, Abstract = {The Slit proteins are a new family of secreted guidance cues involved in axon guidance and neuronal migration. Each mammalian Slit protein contains >1400 amino acid residues, with four leucine-rich regions (LRRs), nine epidermal growth factor repeats, a laminin G domain, and a C-terminal cysteine-rich domain. A receptor for Slit is the transmembrane protein Roundabout (Robo), whose extracellular part contains five Ig domains and three fibronectin type III repeats. We report here that the LRRs in Slit are sufficient for binding to the Ig domains of Robo. Mutant forms of Slit containing only the LRRs function as chemorepellents for axons projecting from the olfactory bulb both in vitro and in the telencephalon. The LRRs can repel neurons migrating from the anterior subventricular zone (SVZa) to the olfactory bulb in brain slices isolated from neonatal rodents. However, the LRRs do not show repulsive effects on the SVZa neurons migrating in collagen gels. Our results indicate that the same LRRs are sufficient for guiding both axon projection and neuronal migration and suggest that the other regions in the Slit proteins may be involved in regulating the diffusion and distribution of the Slit proteins. The fact that the same domains are involved in guiding axon projection and neuronal migration further strengthens the idea of a conserved guidance mechanism for these important processes.}, Author = {Chen, J. H. and Wen, L. and Dupuis, S. and Wu, J. Y. and Rao, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {J Neurosci}, Keywords = {Axons/drug effects/*physiology;Human;Peptide Fragments/pharmacology;Receptors, Immunologic/genetics/metabolism;In Vitro;Rats;Transfection;Nerve Tissue Proteins/genetics/*metabolism/pharmacology;Cell Movement/drug effects;Protein Binding/physiology;Animal;Repetitive Sequences, Amino Acid/physiology;Cell Line;Support, Non-U.S. Gov't;Protein Structure, Tertiary/physiology;Kidney/cytology/metabolism;Coculture;Neurons/cytology/drug effects/*metabolism;Olfactory Bulb/cytology/drug effects/*metabolism;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Leucine/genetics/*metabolism;Amino Acid Motifs;C pdf;Cerebral Ventricles/cytology}, Number = {5}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.}, Pages = {1548-56.}, Title = {The N-terminal leucine-rich regions in Slit are sufficient to repel olfactory bulb axons and subventricular zone neurons}, Uuid = {35E6014A-0541-441F-B978-7AFD4166BB4C}, Volume = {21}, Year = {2001}, url = {papers/Chen_JNeurosci2001}} @article{Chen:2007, Abstract = {Previous studies using dominant-mutant constructs have implicated Rac1 GTPase in neuritogenesis and neuronal migration. However, overexpression of dominant mutants generally blocks Rho-GTPase activity; thus, it may not reveal the specific or physiological functions of Rac1. To address this issue, we have applied a conditional gene-targeting strategy, using Foxg1-Cre mice to delete Rac1 in the ventricular zone (VZ) of telencephalon and Dlx5/6-Cre-IRES (internal ribosomal entry site)-EGFP (enhanced green fluorescent protein) (Dlx5/6-CIE) in the subventricular zone (SVZ) of ventral telencephalon, respectively. Surprisingly, the deletion of Rac1 in VZ progenitors did not prevent axonal outgrowth of telencephalic neurons. However, the anterior commissure was absent, and the corpus callosal as well as hippocampal commissural axons failed to cross the midline in Rac1/Foxg1-Cre knock-out embryos. The thalamocortical and corticothalamic axons also showed defasciculation or projection defects. These results suggest that Rac1 controls axon guidance rather than neuritogenesis. In addition, although Rac1/Foxg1-Cre knock-out embryos showed delayed radial migration of cortical projection neurons and severe impairment of tangential migration by the ventral telencephalon-derived interneurons, deletion of Rac1 in the SVZ by Dlx5/6-CIE mice produced no discernible defects in tangential migration. These contrasting effects of Rac1 deletion on tangential migration suggest that Rac1 is dispensable for cellular motility per se during neuronal migration. Together, these results underscore the challenge of deciphering the biological functions of Rac1, and Rho-GTPases in general, during mammalian brain development. Moreover, they indicate that Rac1 has a critical role in axon guidance and in acquisition of migratory competency during differentiation of the progenitors for the ventral telencephalon-derived interneurons.}, Author = {Chen, Lei and Liao, Guanghong and Waclaw, Ronald R. and Burns, Kevin A. and Linquist, Diana and Campbell, Kenneth and Zheng, Yi and Kuan, Chia-Yi Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Division of Experimental Hematology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.}, Pages = {3884-93}, Pii = {27/14/3884}, Pubmed = {17409253}, Title = {Rac1 controls the formation of midline commissures and the competency of tangential migration in ventral telencephalic neurons}, Uuid = {B7885DB6-4930-401A-82E8-E3A267F96573}, Volume = {27}, Year = {2007}, url = {papers/Chen_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3509-06.2007}} @article{Chen:2001, Abstract = {OBJECT: The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. METHODS: A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. CONCLUSIONS: In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures. Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation. Histological examination of the targeted region did not reveal signs of necrosis. These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy. In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses. However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated. The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy. These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation.}, Author = {Chen, Z. F. and Kamiryo, T. and Henson, S. L. and Yamamoto, H. and Bertram, E. H. and Schottler, F. and Patel, F. and Steiner, L. and Prasad, D. and Kassell, N. F. and Shareghis, S. and Lee, K. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0022-3085}, Journal = {J Neurosurg}, Keywords = {Epilepsy;21 Epilepsy;Treatment Outcome;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Evoked Potentials;Animals;Male;24 Pubmed search results 2008;Radiosurgery;Neurons}, Medline = {21081721}, Month = {2}, Nlm_Id = {0253357}, Number = {2}, Organization = {Department of Neuroscience, University of Virginia Health Sciences Center, Charlottesville 22908, USA.}, Pages = {270-80}, Pubmed = {11213965}, Title = {Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats}, Uuid = {2862ADFF-F71C-4449-ADC8-286763E5BA97}, Volume = {94}, Year = {2001}} @article{Chen:2003b, Abstract = {We developed a rat model of epidural plastic bead implantation to study the effect of physical compression on the cerebral cortex. Epidural implantation of a bead of appropriate size compressed the underlying sensorimotor cortex without apparent ischemia, since the capillary density of the cortex was increased. Although the thickness of all layers of the compressed cortex was significantly decreased, no apparent changes in the number of NADPH-diaphorase reactive neurons, reactive astrocytes, or microglial cells were observed, nor were apoptotic neurons observed. In fact, the densities of the neurons in most cortical layers apparently increased. To determine how epidural compression affects neuronal morphology, the dendritic arbors of layer III and V pyramidal neurons were evaluated using a fixed tissue intracellular dye injection technique. Neurons in both layers remained pyramidal in shape and their somatic sizes remained unaltered for at least a month after compression. On the other hand, their total dendritic length was significantly reduced beginning at 3 days post implantation. These analyses showed that apical dendrites were affected sooner than basal ones. The reduction of dendritic length was associated with a drop in the number of dendritic branches rather than dendritic trunks, suggesting the trimming of the peripheral part of the dendritic arbor. Detailed analysis showed that dendritic spines on all dendrites were reduced as early as 3 days following implantation. These results suggest that cortical neurons remodel their structures substantially within 3 days after being subjected to epidural compression.}, Author = {Chen, Jeng-Rung R. and Wang, Yueh-Jan J. and Tseng, Guo-Fang F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0897-7151}, Journal = {J Neurotrauma}, Keywords = {Laterality;10 Development;NADPH Dehydrogenase;Rats;Female;Astrocytes;Rats, Wistar;Microglia;Epidural Space;10 Structural plasticity;Support, Non-U.S. Gov't;Animals;Cerebral Cortex;Neurons;Beta}, Medline = {22846858}, Month = {8}, Nlm_Id = {8811626}, Number = {8}, Organization = {Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.}, Pages = {767-80}, Pubmed = {12965055}, Title = {The effect of epidural compression on cerebral cortex: a rat model}, Uuid = {8711D255-748A-4F13-A902-25B2876A8B2E}, Volume = {20}, Year = {2003}, url = {papers/Chen_JNeurotrauma2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/089771503767869999}} @article{Chen:2005c, Abstract = {Caspase activation occurs within 1h of reperfusion in discrete cell populations of the adult rat brain following transient forebrain ischemia. Based on the proximity of these cells to regions of adult neurogenesis and the known susceptibility of developing neurons to apoptosis, we tested the hypothesis that rapidly triggered post-ischemic caspase activation occurs in immature neurons or neuroprogenitor cells. Adult male Long Evans rats were injected with BrdU to label mitotic cells 1, 7, or 28 days prior to being studied. Rats were then subjected to either sham surgery or 10-min transient forebrain ischemia. At 1h after reperfusion, rats underwent perfusion fixation and brains prepared for immunohistochemical analysis. Immunolabeling for caspase-substrate cleavage, using an antibody directed at the caspase derived fragment of alpha-spectrin, was observed in discrete cell populations of the rostral dentate gyrus, dorsal striatum, extreme paramedian CA1 hippocampus, indusium gresium, olfactory tubercle, and thalamus. No cells double-labeled for caspase-substrate cleavage and BrdU at any time point after BrdU injection. Furthermore, cells immunolabeled for caspase-substrate cleavage did not double-label for markers of immature neurons (doublecortin) or progenitor cells (nestin), but did double-label for the mature neuronal marker NeuN. These results indicate that the phenomenon of rapidly triggered caspase activation in the adult rat brain after transient forebrain ischemia is specific to mature neurons and does not occur in neuroprogenitor cells or immature neurons.}, Author = {Chen, Zhaoming and Kontonotas, Diana and Friedmann, Daniel and Pitts-Kiefer, Alex and Frederick, James R. and Siman, Robert and Neumar, Robert W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7600130}, Number = {3}, Organization = {Department of Emergency Medicine, University of Pennsylvania School of Medicine, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.}, Pages = {166-70}, Pii = {S0304-3940(04)01462-4}, Pubmed = {15721215}, Title = {Developmental status of neurons selectively vulnerable to rapidly triggered post-ischemic caspase activation}, Uuid = {BDFF59EE-50B4-4B31-B92F-ACDDD8F34947}, Volume = {376}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2004.11.051}} @article{Chen:2004, Abstract = {The adult mammalian CNS shows a very limited capacity to regenerate after injury. However, endogenous precursors, or stem cells, provide a potential source of new neurons in the adult brain. Here, we induce the birth of new corticospinal motor neurons (CSMN), the CNS neurons that die in motor neuron degenerative diseases, including amyotrophic lateral sclerosis, and that cause loss of motor function in spinal cord injury. We induced synchronous apoptotic degeneration of CSMN and examined the fates of newborn cells arising from endogenous precursors, using markers for DNA replication, neuroblast migration, and progressive neuronal differentiation, combined with retrograde labeling from the spinal cord. We observed neuroblasts entering the neocortex and progressively differentiating into mature pyramidal neurons in cortical layer V. We found 20-30 new neurons per mm(3) in experimental mice vs. 0 in controls. A subset of these newborn neurons projected axons into the spinal cord and survived >56 weeks. These results demonstrate that endogenous precursors can differentiate into even highly complex long-projection CSMN in the adult mammalian brain and send new projections to spinal cord targets, suggesting that molecular manipulation of endogenous neural precursors in situ may offer future therapeutic possibilities for motor neuron degenerative disease and spinal cord injury.}, Author = {Chen, Jinhui and Magavi, Sanjay S. P. and Macklis, Jeffrey D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;Research Support, Non-U.S. Gov't;17 Transplant Regeneration;Motor Neurons;Nerve Regeneration;Female;Apoptosis;Research Support, U.S. Gov't, P.H.S.;Neural Pathways;Mice, Inbred C57BL;Stem Cells;06 Adult neurogenesis injury induced;Spinal Cord;Animals;Mice;Cerebral Cortex;Neurons}, Month = {11}, Nlm_Id = {7505876}, Number = {46}, Organization = {Department of Neurosurgery and Program in Neuroscience, Massachusetts General Hospital-Harvard Medical School Center for Nervous System Repair, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.}, Pages = {16357-62}, Pii = {0406795101}, Pubmed = {15534207}, Title = {Neurogenesis of corticospinal motor neurons extending spinal projections in adult mice}, Uuid = {5196DFAF-E740-41F8-A7C2-2E9C4D92C43A}, Volume = {101}, Year = {2004}, url = {papers/Chen_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0406795101}} @article{Chen:2005, Abstract = {Pyramidal neurons of the cerebral cortex display marked layer- and subtype-specific differences in their axonal projections and dendritic morphologies. Here we show that transcription factor Zfp312 is selectively expressed by layer V and VI subcortical projection pyramidal neurons and their progenitor cells. Knocking down Zfp312 with small interfering RNAs dramatically reduced the number of subcortical axonal projections from deep-layer pyramidal neurons and altered their dendritic morphology. In contrast, misexpression of Zfp312 in cortically projecting pyramidal neurons of layers II and III induced the expression of Tbr1, a transcription factor enriched in deep-layer neurons, and the formation of ectopic subcortical axonal projections. Thus, our results indicate that transcription factor Zfp312 plays a critical role in layer- and neuronal subtype-specific patterning of cortical axonal projections and dendritic morphologies.}, Author = {Chen, and Rasin, and Kwan, and Sestan,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {10 Development}, Month = {11}, Nlm_Id = {7505876}, Organization = {Department of Neurobiology and Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510.}, Pii = {0509032102}, Pubmed = {16314561}, Title = {Zfp312 is required for subcortical axonal projections and dendritic morphology of deep-layer pyramidal neurons of the cerebral cortex}, Uuid = {9347FA49-9ED5-4438-B495-8DE8D24EE662}, Year = {2005}, url = {papers/Chen_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0509032102}} @article{Chen:2005a, Abstract = {During the development of the cerebral cortex, progenitor cells produce neurons that migrate to laminar positions appropriate for their birth dates, adopt specific neuronal identities, and form appropriate local and long-distance axonal connections. Here, we report that forebrain embryonic zinc-finger-like protein (Fezl), a putative zinc-finger transcriptional repressor, is required for the differentiation of projection neurons in cortical layer 5. In Fezl-deficient mice, these neurons display molecular, morphological, and axonal targeting defects. The corticospinal tract was absent in Fezl(-/-) mice, corticotectal and pontine projections were severely reduced, and Fezl-expressing neurons formed aberrant axonal projections. The expression of many molecular markers for deep-layer neurons was reduced or absent in the Fezl(-/-) cerebral cortex. Most strikingly, Ctip2, a transcription factor required for the formation of the corticospinal tract, was not expressed in the Fezl-deficient cortex. These results suggest that Fezl regulates the differentiation of layer 5 subcortical projection neurons.}, Author = {Chen, Bin and Schaevitz, Laura R. and McConnell, Susan K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {10 Development;Cell Differentiation;Heterozygote;Animals;DNA-Binding Proteins;Humans;Neural Pathways;Axons;Staining and Labeling;Zinc Fingers;Mice, Knockout;Cerebral Cortex;Motor Neurons;Mice;research support, n.i.h., extramural;Genes, Reporter;24 Pubmed search results 2008;Nerve Tissue Proteins;Repressor Proteins;Genetic Markers}, Month = {11}, Nlm_Id = {7505876}, Number = {47}, Organization = {Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA.}, Pages = {17184-9}, Pii = {0508732102}, Pubmed = {16284245}, Title = {Fezl regulates the differentiation and axon targeting of layer 5 subcortical projection neurons in cerebral cortex}, Uuid = {47027172-2F0E-4655-9C93-9F865549D39A}, Volume = {102}, Year = {2005}, url = {papers/Chen_ProcNatlAcadSciUSA2005a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0508732102}} @article{Chen:2003, Abstract = {Mutations in MeCP2, which encodes a protein that has been proposed to function as a global transcriptional repressor, are the cause of Rett syndrome (RT T), an X-linked progressive neurological disorder. Although the selective inactivation of MeCP2 in neurons is sufficient to confer a Rett-like phenotype in mice, the specific functions of MeCP2 in postmitotic neurons are not known. We find that MeCP2 binds selectively to BDNF promoter III and functions to repress expression of the BDNF gene. Membrane depolarization triggers the calcium-dependent phosphorylation and release of MeCP2 from BDNF promoter III, thereby facilitating transcription. These studies indicate that MeCP2 plays a key role in the control of neuronal activity-dependent gene regulation and suggest that the deregulation of this process may underlie the pathology of RT T.}, Author = {Chen, Wen G. and Chang, Qiang and Lin, Yingxi and Meissner, Alexander and West, Anne E. and Griffith, Eric C. and Jaenisch, Rudolf and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Methyl-CpG-Binding Protein 2;24 Pubmed search results 2008;Gene Silencing;Animals;Cells, Cultured;Transcription, Genetic;Methylation;CpG Islands;Rett Syndrome;Promoter Regions (Genetics);Histones;Chromosomal Proteins, Non-Histone;research support, u.s. gov't, p.h.s.;Electrophoretic Mobility Shift Assay;Brain-Derived Neurotrophic Factor;Potassium Chloride;DNA-Binding Proteins;Gene Expression Regulation;Cell Membrane;Calcium;Cloning, Molecular;Rats;Repressor Proteins;research support, non-u.s. gov't;21 Neurophysiology;Mice, Knockout;DNA Methylation;Phosphorylation;Neurons;Mice;Precipitin Tests}, Month = {10}, Nlm_Id = {0404511}, Number = {5646}, Organization = {Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {885-9}, Pii = {302/5646/885}, Pubmed = {14593183}, Title = {Derepression of BDNF transcription involves calcium-dependent phosphorylation of MeCP2}, Uuid = {F957E10E-5CA4-4705-AF9A-3C144BFFC6C4}, Volume = {302}, Year = {2003}, url = {papers/Chen_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1086446}} @article{Chen:2005b, Abstract = {Cell-cell fusion is fundamental to the development and physiology of multicellular organisms, but little is known of its mechanistic underpinnings. Recent studies have revealed that many proteins involved in cell-cell fusion are also required for seemingly unrelated cellular processes such as phagocytosis, cell migration, axon growth, and synaptogenesis. We review advances in understanding cell-cell fusion by contrasting it with virus-cell and intracellular vesicle fusion. We also consider how proteins involved in general aspects of membrane dynamics have been co-opted to control fusion of diverse cell types by coupling with specialized proteins involved in cell-cell recognition, adhesion, and signaling.}, Author = {Chen, Elizabeth H. and Olson, Eric N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {08 Aberrant cell cycle;11 Glia;15 Retrovirus mechanism}, Month = {4}, Nlm_Id = {0404511}, Number = {5720}, Organization = {Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. echen\@jhmi.edu}, Pages = {369-73}, Pii = {308/5720/369}, Pubmed = {15831748}, Title = {Unveiling the mechanisms of cell-cell fusion}, Uuid = {13A0E6EF-EE5E-11DA-8605-000D9346EC2A}, Volume = {308}, Year = {2005}, url = {papers/Chen_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1104799}} @article{Chen:2000b, Abstract = {Lentiviral vectors efficiently transduce human CD34(+) cells that mediate long-term engraftment of nonobese diabetic/severe combined immunodeficient mice. However, hematopoiesis in these animals is abnormal. Typically, 95\%of the human cells in peripheral blood are B lymphocytes. To determine whether lentiviral vectors efficiently transduce stem cells that maintain normal hematopoiesis in vivo, we isolated Sca-1(+)c-Kit(+)Lin(-) bone marrow cells from mice without 5-fluorouracil treatment, and transduced these cells in the absence of cytokine stimulation with a novel lentiviral vector containing a GFP (green flourescent protein) reporter gene. These cells were transplanted into lethally irradiated C57Bl/6 mice. In fully reconstituted animals, GFP expression was observed in 8.0\%of peripheral blood mononuclear cells for 20 weeks posttransplantation. Lineage analysis demonstrated that a similar percentage (approximately 8.0\%) of GFP-positive cells was detected in peripheral blood B cells, T cells, granulocytes and monocytes, bone marrow erythroid precursor cells, splenic B cells, and thymic T cells. In secondary transplant recipients, up to 20\%of some lineages expressed GFP. Our results suggest that quiescent, hematopoietic stem cells are efficiently transduced by lentiviral vectors without impairing self-renewal and normal lineage specification in vivo. Efficient gene delivery into murine stem cells with lentiviral vectors will allow direct tests of genetic therapies in mouse models of hematopoietic diseases such as sickle cell anemia and thalassemia, in which corrected cells may have a selective survival advantage.}, Author = {Chen, W. and Wu, X. and Levasseur, D. N. and Liu, H. and Lai, L. and Kappes, J. C. and Townes, T. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {T-Lymphocytes;Cell Differentiation;Animals;Humans;Whole-Body Irradiation;Transfection;Lentivirus;B-Lymphocytes;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Hematopoietic Stem Cell Transplantation;Genetic Vectors;Research Support, U.S. Gov't, P.H.S.;Thymus Gland;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Genes, Reporter;Spleen;Research Support, Non-U.S. Gov't}, Medline = {20465652}, Nlm_Id = {9304532}, Number = {5}, Organization = {Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Alabama, USA.}, Pages = {352-9}, Pubmed = {11007919}, Title = {Lentiviral vector transduction of hematopoietic stem cells that mediate long-term reconstitution of lethally irradiated mice}, Uuid = {97EFD9CA-4768-4FA2-826D-729DE3E23B96}, Volume = {18}, Year = {2000}} @article{Chen:2003c, Abstract = {In the course of normal embryogenesis, embryonic stem (ES) cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue structures. In order to study this phenomenon in vitro under controlled conditions, 3D culture systems are necessary. Here, we studied in vitro differentiation of rhesus monkey ES cells in 3D collagen matrixes (collagen gels and porous collagen sponges). Differentiation of ES cells in these 3D systems was different from that in monolayers. ES cells differentiated in collagen matrixes into neural, epithelial, and endothelial lineages. The abilities of ES cells to form various structures in two chemically similar but topologically different matrixes were different. In particular, in collagen gels ES cells formed gland-like circular structures, whereas in collagen sponges ES cells were scattered through the matrix or formed aggregates. Soluble factors produced by feeder cells or added to the culture medium facilitated ES cell differentiation into particular lineages. Coculture with fibroblasts in collagen gel facilitated ES cell differentiation into cells of a neural lineage expressing nestin, neural cell adhesion molecule, and class III beta-tubulin. In collagen sponges, keratinocytes facilitated ES cell differentiation into cells of an endothelial lineage expressing factor VIII. Exogenous granulocyte-macrophage colony-stimulating factor further enhanced endothelial differentiation. Thus, both soluble factors and the type of extracellular matrix seem to be critical in directing differentiation of ES cells and the formation of tissue-like structures. Three-dimensional culture systems are a valuable tool for studying the mechanisms of these phenomena.}, Author = {Chen, Silvia S. and Revoltella, Roberto P. and Papini, Sandra and Michelini, Monica and Fitzgerald, Wendy and Zimmerberg, Joshua and Margolis, Leonid}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {Cytokines;Cell Differentiation;Cell Culture Techniques;Animals;Cells, Cultured;Research Support, U.S. Gov't, Non-P.H.S.;Diffusion Chambers, Culture;Culture Media, Conditioned;Extracellular Matrix;Gelatin Sponge, Absorbable;Macaca mulatta;Gels;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;Pluripotent Stem Cells;Cell Division;Immunohistochemistry;22 Stem cells;Biological Markers;Collagen;Research Support, Non-U.S. Gov't}, Medline = {22628933}, Nlm_Id = {9304532}, Number = {3}, Organization = {NASA/NIH Center for Three Dimensional Tissue Culture, Laboratory of Cellular and Molecular Biophysics, National Institute of Child Health and Human Development (NICHD), NIH, Bethesda, Maryland 20892, USA.}, Pages = {281-95}, Pubmed = {12743323}, Title = {Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems}, Uuid = {3F3C87F1-217B-4784-BAB4-0A543614B6A4}, Volume = {21}, Year = {2003}, url = {papers/Chen_StemCells2003.pdf}} @article{Cheng:2005, Abstract = {The complexity and cellular diversity of the adult brain arises from the proliferation and differentiation of a small number of stem cells. The intrinsic state of stem cells depends on their spatial and temporal history and affects their responsiveness to extrinsic signals from the microenvironment. Stem cell self-renewal and differentiation along neuronal and glial lineages are defined by the dynamic interplay between transcription, epigenetic control, and posttranscriptional regulators, including microRNAs, whose key role in stem cell biology is just emerging.}, Author = {Cheng, Li-Chun C. and Tavazoie, Masoud and Doetsch, Fiona}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-13 09:45:17 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development; MicroRNAs; microRNAs; development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Pathology, Columbia University, 630 West 168th Street, New York, New York 10032, USA.}, Pages = {363-7}, Pii = {S0896-6273(05)00363-6}, Pubmed = {15882632}, Title = {Stem cells: from epigenetics to microRNAs}, Uuid = {F81A60FF-D4D9-4208-82AE-E0615BC1F841}, Volume = {46}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.027}} @article{Chenn:1995, Abstract = {Neurons in the mammalian central nervous system are generated from progenitor cells near the lumen of the neural tube. Time-lapse microscopy of dividing cells in slices of developing cerebral cortex reveals that cleavage orientation predicts the fates of daughter cells. Vertical cleavages produce behaviorally and morphologically identical daughters that resemble precursor cells; these symmetric divisions may serve to expand or maintain the progenitor pool. In contrast, horizontally dividing cells produce basal daughters that behave like young migratory neurons and apical daughters that remain within the proliferative zone. Notch1 immunoreactivity is distributed asymmetrically in mitotic cells, with Notch1 inherited selectively by the basal (neuronal) daughter of horizontal divisions. These results provide cellular and molecular evidence that cortical neurons are generated from asymmetric divisions. 95393475 0092-8674 Journal Article}, Author = {Chenn, A. and McConnell, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Cell}, Keywords = {Stem Cells/cytology/metabolism;Neurons/cytology/metabolism;10 Development;Immunohistochemistry;Time Factors;Cell Division;Ferrets;Animal;Support, U.S. Gov't, Non-P.H.S.;F;Cerebral Cortex/cytology/embryology/*metabolism;Cell Polarity;Support, U.S. Gov't, P.H.S.;Membrane Proteins/*genetics/metabolism}, Number = {4}, Organization = {Department of Biological Sciences, Stanford University, California 94305, USA.}, Pages = {631-41}, Pubmed = {7664342}, Title = {Cleavage orientation and the asymmetric inheritance of Notch1 immunoreactivity in mammalian neurogenesis}, Uuid = {1BBA55CA-7A69-407F-8633-A5566034CE26}, Volume = {82}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7664342}} @article{Chenn:2005, Abstract = {Asymmetric cell division plays a major role in the generation of cell diversity during development. In this issue of Neuron, Sun and colleagues present evidence that the epidermal growth factor receptor is asymmetrically distributed in mitotic cerebral cortical precursors, and the resulting unequal inheritance generates offspring with different responsiveness to growth factor and unique cell fates.}, Author = {Chenn, Anjen}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {review;Cell Differentiation;10 Development;Neuroglia;Receptor, Epidermal Growth Factor;Stem Cells;Cell Division;review, tutorial;comment;Brain Neoplasms;Humans;Animals;Cerebral Cortex;Cell Lineage;Neurons}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Pathology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.}, Pages = {817-9}, Pii = {S0896-6273(05)00193-5}, Pubmed = {15797541}, Title = {The simple life (of cortical progenitors)}, Uuid = {0BDA0140-672B-4098-ADC5-BE62EFE32763}, Volume = {45}, Year = {2005}, url = {papers/Chenn_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.03.001}} @article{Chenn:2002, Abstract = {Transgenic mice expressing a stabilized beta-catenin in neural precursors develop enlarged brains with increased cerebral cortical surface area and folds resembling sulci and gyri of higher mammals. Brains from transgenic animals have enlarged lateral ventricles lined with neuroepithelial precursor cells, reflecting an expansion of the precursor population. Compared with wild-type precursors, a greater proportion of transgenic precursors reenter the cell cycle after mitosis. These results show that beta-catenin can function in the decision of precursors to proliferate or differentiate during mammalian neuronal development and suggest that beta-catenin can regulate cerebral cortical size by controlling the generation of neural precursor cells. 1095-9203 Journal Article}, Author = {Chenn, A. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Science}, Keywords = {Cell Differentiation;Apoptosis;Fungal Proteins/genetics/metabolism;Stem Cells/cytology/metabolism/*physiology;Mitosis;*Cell Cycle;Antibodies, Monoclonal;10 Development;Animals;Repressor Proteins/genetics/metabolism;*Trans-Activators;*Saccharomyces cerevisiae Proteins;Extracellular Matrix Proteins/genetics/metabolism;Signal Transduction;Cell Count;Brain/anatomy &histology/embryology;Cell Division;In Situ Hybridization;Recombinant Fusion Proteins/metabolism;Epithelium/embryology;Cerebral Cortex/anatomy &histology/*embryology/metabolism;Support, U.S. Gov't, P.H.S.;Neurons/cytology/metabolism/*physiology;Ki-67 Antigen/genetics/metabolism;Cell Adhesion Molecules, Neuronal/genetics/metabolism;F pdf;DNA-Binding Proteins/genetics/metabolism;Cytoskeletal Proteins/genetics/*metabolism;Mice;Support, Non-U.S. Gov't;Mice, Transgenic}, Number = {5580}, Organization = {Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.}, Pages = {365-9}, Pubmed = {12130776}, Title = {Regulation of cerebral cortical size by control of cell cycle exit in neural precursors}, Uuid = {72779634-C4B4-4F81-92DE-5E84F2E749A9}, Volume = {297}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12130776}} @article{Chernoff:1996, Abstract = {Studies of neuronal survival and axonal regeneration in birds and mammals have made it clear that the microenvironment of the CNS is critical to the failure of CNS regeneration in these animals. This environment includes growth and trophic factors, ECM components and matrix turnover enzymes, cytokines and other immune system contributions. Urodele amphibians (salamanders and newts) can regenerate spinal cord even as adults, and environmental contributions of glial populations are a major part of the difference between urodele and higher vertebrate spinal cord regeneration. In particular, the behavior of injury-reactive ependymal cells (radial glia) is critical to the regenerative capacity of urodele spinal cord. In this review we examine what is known about cell-cell interactions between ependymal cells and neurons and between ependymal cells and other glial populations. The known contributions of ependymal cell products such as matrix metalloproteinases and trophic factors are discussed. There is evidence in the literature that an ependymal response occurs during embryonic or fetal development in birds and mammals following spinal cord transection, and this review discusses the implications of such a process for future studies of spinal cord injury. 0214-6282 Journal Article Review Review, Tutorial}, Author = {Chernoff, E. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {Int J Dev Biol}, Keywords = {17 Transplant Regeneration;Cell Communication;Rats;Chick Embryo;Growth Substances/physiology;Spinal Cord/*physiology;L pdf;Urodela/*physiology;Animals;*Regeneration;Ependyma/cytology;Intermediate Filament Proteins/physiology}, Number = {4}, Organization = {Department of Biology, Indiana University-Purdue University at Indianapolis, 46202-5132, USA. echernof\@indyvax.iupui.edu}, Pages = {823-31}, Title = {Spinal cord regeneration: a phenomenon unique to urodeles?}, Uuid = {4A5D455E-59DB-4472-9185-E50FD648CE80}, Volume = {40}, Year = {1996}, url = {papers/Chernoff_IntJDevBiol1996.pdf}} @article{Chesler:1992, Abstract = {Although the requirement for a strict regulation of pH in the brain is frequently emphasized, recent studies indicate that neuronal activity gives rise to significant changes in intracellular and extracellular pH. Given the sensitivity of many ion channels to hydrogen ions, this modulation of local pH might influence brain function, particularly where pH shifts are sufficiently large and rapid. Studies using pH-sensitive microelectrodes have demonstrated marked cellular and regional variability of activity-dependent pH shifts, and have begun to uncover several of their underlying mechanisms. Accumulating evidence suggests that regional and subcellular pH dynamics are governed by the respective localization of glial cells, ligand-gated ion channels, and extracellular and intracellular carbonic anhydrase.}, Author = {Chesler, M. and Kaila, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;11 Glia;Animals;Hydrogen-Ion Concentration;Humans;Neurons;review}, Medline = {93069538}, Month = {10}, Nlm_Id = {7808616}, Number = {10}, Organization = {Dept of Physiology and Biophysics, New York University Medical Center, NY 10016.}, Pages = {396-402}, Pii = {0166-2236(92)90191-A}, Pubmed = {1279865}, Title = {Modulation of pH by neuronal activity}, Uuid = {E2ED6E40-EE2E-11DA-8605-000D9346EC2A}, Volume = {15}, Year = {1992}} @article{Chevaleyre:2002, Abstract = {Developing oxytocin and vasopressin (OT/AVP) supraoptic nucleus (SON) neurons positively autocontrol their electrical activity via dendritic release of their respective peptide. The effects of this autocontrol are maximum during the second postnatal week (PW2), when the dendritic arbor transiently increases and glutamatergic postsynaptic potentials appear. Here, we studied the role and interaction of dendritic OT/AVP release and glutamate release in dendritic plasticity and synaptogenesis in SON. In vivo treatment with the peptides antagonists or with an NMDA antagonist suppressed the transient increase in dendritic arbor of SON neurons at the beginning of PW2. Incubation of acute slices with these compounds decreased the dendritic arbor on a short time scale (3-8 hr) in slices of postnatal day 7 (P7) to P9 rats. Conversely, application of OT/AVP or NMDA increased dendritic branches in slices of P3-P6 rats. Their effects were inhibited by blockade of electrical activity, voltage-gated Ca2+ channels, or intracellular Ca2+ mobilization. They were also interdependent because both OT/AVP and NMDA (but not AMPA) receptor activation were required for increasing the dendritic arbor. Part of this interdependence probably results from a retrograde action of the peptides facilitating glutamate release. Finally, blocking OT/AVP receptors by in vivo treatment with the peptides antagonists during development decreased spontaneous glutamatergic synaptic activity recorded in young adults. These results show that an interplay between postsynaptic dendritic peptide release and presynaptic glutamate release is involved in the transient increase in dendritic arbor of SON neurons and indicate that OT/AVP are required for normal synaptogenesis of glutamatergic inputs in SON.}, Author = {Chevaleyre, V. and Moos, F. C. and Desarmenien, M. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;13 Olfactory bulb anatomy;N-Methylaspartate/pharmacology;In Vitro;I;Synaptic Transmission/drug effects;Rats;Neurons/drug effects/metabolism;Excitatory Amino Acid Antagonists/pharmacology;Oxytocin/antagonists &inhibitors/pharmacology;Morpholines/pharmacology;Animal;Microinjections;Dendrites/*physiology/ultrastructure;Receptors, N-Methyl-D-Aspartate/antagonists &inhibitors/metabolism;Supraoptic Nucleus/drug effects/*physiology/ultrastructure;Calcium/metabolism;Presynaptic Terminals/drug effects/physiology/ultrastructure;Pyrrolidines/pharmacology;Argipressin/antagonists &inhibitors/pharmacology;Support, Non-U.S. Gov't;Neuronal Plasticity/drug effects/*physiology;Hormone Antagonists/pharmacology;Indoles/pharmacology;Synapses/drug effects/*physiology/ultrastructure;Spiro Compounds/pharmacology}, Number = {1}, Organization = {Centre National de la Recherche Scientifique Unite Mixte de Recherche 5101, Biologie des Neurones Endocrines, 34094 Montpellier Cedex 5, France.}, Pages = {265-73.}, Title = {Interplay between presynaptic and postsynaptic activities is required for dendritic plasticity and synaptogenesis in the supraoptic nucleus}, Uuid = {A17B1A16-68DD-4EE1-9985-E2D84EA8EE01}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11756510%20http://www.jneurosci.org/cgi/content/full/22/1/265%20http://www.jneurosci.org/cgi/content/abstract/22/1/265}} @article{Chevassus-Au-Louis:1999b, Abstract = {Prenatal treatment with methylazoxymethanol (MAM) in rats generates animals with a diffuse cortical malformation associated with hyperexcitability. These alterations are reminiscent of the cortical malformations associated with epilepsy in children. We hypothesised that one of the mechanisms supporting hyperexcitability in MAM rats could be the presence of abnormal cortical connections in the malformed cortex. Using a variety of anatomical techniques, we provide evidences for three types of such abnormal connections: (i) tangential bundles of corticocortical fibres in and below the neocortical molecular layer; (ii) partial deafferentation of neocortical heterotopias by afferent cortical fibres whatever their location; (iii) exuberant innervation of hippocampal CA3 pyramidal cells by mossy fibres that form ectopic mossy boutons on their basal dendrites. We conclude that these abnormal intrinsic cortical connections may support the propagation of paroxymal activity in the neocortex of MAM-treated rats. Copyright Copyright 1999 S. Karger AG, Basel}, Author = {Chevassus-Au-Louis, N. and Jorquera, I. and Ben-Ari, Y. and Represa, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Teratogens;10 Development;Female;Hippocampus;Neural Pathways;Rats;Rats, Wistar;Methylazoxymethanol Acetate;Neocortex;Abnormalities, Drug-Induced;Pregnancy;10 genetics malformation;Animals;24 Pubmed search results 2008;Cerebral Cortex;Embryo, Mammalian}, Month = {11}, Nlm_Id = {7809375}, Number = {3-5}, Organization = {Inserm U29, H\^{o}pital de Port-Royal, Paris, France.}, Pages = {385-92}, Pii = {dne21385}, Pubmed = {10575262}, Title = {Abnormal connections in the malformed cortex of rats with prenatal treatment with methylazoxymethanol may support hyperexcitability}, Uuid = {16663AA0-9429-4FA2-8EB4-F851702D8C79}, Volume = {21}, Year = {1999}} @article{Chevassus-Au-Louis:1998a, Abstract = {Migration disorders cause neurons to differentiate in an abnormal heterotopic position. Although significant insights have been gained into the etiology of these disorders, very little is known about the anatomy of heterotopias. We have studied heterotopic masses arising in the hippocampal CA1 region after prenatal treatment with methylazoxymethanol (MAM) in rats. Heterotopic cells were phenotypically similar to neocortical supragranular neurons and exhibited the same temporal profile of migration and neurogenesis. However, they did not express molecules characteristic of CA1 neurons such as the limbic-associated membrane protein. Horseradish peroxidase injections in heterotopia demonstrated labeled fibers not only in the neocortex and white matter but also in the CA1 stratum radiatum and stratum lacunosum. To study the pathophysiological consequences of this connectivity, we compared the effects of neocortical and limbic seizures on the expression of Fos protein and on cell death in MAM animals. After metrazol-induced seizures, Fos-positive cells were present in CA1 heterotopias, the only hippocampal region to be activated with the neocortex. By contrast, kainic acid-induced seizures caused a prominent delayed cell death in limbic regions and in CA1 heterotopias. Together, these results suggest that neocortical heterotopias in the CA1 region are integrated in both the hippocampal and neocortical circuitry.}, Author = {Chevassus-Au-Louis, N. and Rafiki, A. and Jorquera, I. and Ben-Ari, Y. and Represa, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {10 Development;Pregnancy;Animals;Rats;Mitosis;Neocortex;Female;Cell Movement;Hippocampus;Rats, Wistar;research support, non-u.s. gov't;In Situ Hybridization;Animals, Newborn;10 genetics malformation;Methylazoxymethanol Acetate;Neurons;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Bromodeoxyuridine;Choristoma;Brain Mapping}, Month = {5}, Nlm_Id = {0406041}, Number = {4}, Organization = {INSERM Unit{\'e} 29, Universit{\'e} Paris 5 Ren{\'e} Descartes, France. chevassus\@cochin.inserm.fr}, Pages = {520-36}, Pii = {10.1002/(SICI)1096-9861(19980518)394:4<520::AID-CNE9>3.0.CO;2-3}, Pubmed = {9590559}, Title = {Neocortex in the hippocampus: an anatomical and functional study of CA1 heterotopias after prenatal treatment with methylazoxymethanol in rats}, Uuid = {0326F3A7-89A4-4121-AC5B-4B40820AEC63}, Volume = {394}, Year = {1998}} @article{Chevassus-Au-Louis:1998, Abstract = {Neuronal migration disorders have been involved in various pathologies, including epilepsy, but the properties of the neural networks underlying disorders have not been determined. In the present study, patch clamp recordings were made from intrahippocampal heterotopic as well as from neocortical and hippocampal neurons from brain slices of rats with prenatally methylazoxymethanol-induced cortical malformation. We report that heterotopic neurons have morphometrical parameters and cellular properties of neocortical supragranular neurons and are integrated in both neocortical and hippocampal networks. Thus, stimulation of the white matter induces both antidromic and orthodromic response in heterotopic and neocortical neurons. Stimulation of hippocampal afferents evokes a monosynaptic response in the majority of heterotopic neurons and a polysynaptic all-or-none epileptiform burst in the presence of bicuculline to block gamma-aminobutyric acid type A inhibition. Furthermore, hippocampal paroxysmal activity generated by bath application of bicuculline can spread directly to the neocortex via the heterotopia in methylazoxymethanol-treated but not in naive rats. We conclude that heterotopias form a functional bridge between the limbic system and the neocortex, providing a substrate for pathological conditions.}, Author = {Chevassus-Au-Louis, N. and Congar, P. and Represa, A. and Ben-Ari, Y. and Ga{\"\i}arsa, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {10 Development;Pregnancy;Electric Stimulation;Electrophysiology;Animals;Rats;21 Epilepsy;Neocortex;Female;Patch-Clamp Techniques;Cell Movement;Hippocampus;21 Dysplasia-heterotopia;Pyramidal Cells;Rats, Wistar;Teratogens;Nerve Net;Action Potentials;10 genetics malformation;21 Neurophysiology;Methylazoxymethanol Acetate;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {98374340}, Month = {8}, Nlm_Id = {7505876}, Number = {17}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U29, Universit{\'e} Paris 5 Ren{\'e} Descartes, 123 Boulevard de Port Royal, 75 674 Paris cedex 14, France. chevassus\@cochin.inserm.fr}, Pages = {10263-8}, Pubmed = {9707635}, Title = {Neuronal migration disorders: heterotopic neocortical neurons in CA1 provide a bridge between the hippocampus and the neocortex}, Uuid = {5E9DC354-015B-11DB-9E68-000D9346EC2A}, Volume = {95}, Year = {1998}, url = {papers/Chevassus-Au-Louis_ProcNatlAcadSciUSA1998.pdf}} @article{Chevassus-au-Louis:1999c, Abstract = {During the development of the neocortex, neurogenesis and neuronal differentiation occur in two separate locations. Thus neurons have to migrate through the future white matter. Arrested or excessive migration leads neurons to differentiate in a heterotopic position. Such neuronal migration disorders (NMDs) occur sporadically in normal development but are markedly increased as a consequence of genetic defects or after exposure to toxic drugs during the period of migration. Anatomofunctional studies in rodents with NMDs have revealed that heterotopic neurons form essentially normal afferent and efferent connections, which has been interpreted as evidence that the connection pattern of cortical neurons is specified prior to migration. In addition, recent data show that heterotopic neurons can be contacted by environmental, that is local, fibres that normally never innervate the neocortex. This dual connectivity leads heterotopias to form bridges between their environmental and original network. Such an abnormal pattern of connectivity could contribute to the pathophysiology of disorders associated with NMDs such as epilepsy.}, Author = {Chevassus-au-Louis, N. and Represa, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {1420-682X}, Journal = {Cell Mol Life Sci}, Keywords = {24 Pubmed search results 2008;Brain Diseases;10 Development;Choristoma;Neocortex;10 genetics malformation;Animals;Humans;Cerebral Cortex;Neurons;review}, Month = {8}, Nlm_Id = {9705402}, Number = {10}, Organization = {INSERM U29, Paris, France. chevassus\@cochin.inserm.fr}, Pages = {1206-15}, Pubmed = {10487203}, Title = {The right neuron at the wrong place: biology of heterotopic neurons in cortical neuronal migration disorders, with special reference to associated pathologies}, Uuid = {96A92A93-ABCA-469A-BFDC-02980E7B4244}, Volume = {55}, Year = {1999}} @article{Chevassus-au-Louis:1999, Abstract = {In the last decade, the recognition of the high frequency of cortical malformations among patients with epilepsy especially children, has led to a renewed interest in the study of the pathophysiology of cortical development. This field has also been spurred by the recent development of several experimental genetic and non-genetic, primarily rodent, models of cortical malformations. Epileptiform activity in these animals can appear as spontaneous seizure activity in vivo, in vitro hyperexcitability, or reduced seizure susceptibility in vitro and in vivo. In the neonatal freeze lesion model, that mimics human microgyria, hyperexcitability is caused by a reorganization of the network in the borders of the malformation. In the prenatal methylazoxymethanol model, that causes a diffuse cortical malformation, hyperexcitability is associated with alteration of firing properties of discrete neuronal subpopulations together with the formation of bridges between normally unconnected structures. In agreement with clinical evidence, these experimental data suggest that cortical malformations can both form epileptogenic foci and alter brain development in a manner that causes a diffuse hyperexcitability of the cortical network.}, Author = {Chevassus-au-Louis, N. and Baraban, S. C. and Ga{\"\i}arsa, J. L. and Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:42 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Humans;Rats;Neural Pathways;Mitosis;Neural Conduction;21 Epilepsy;review;Epilepsy;Mutation;Hippocampus;Abnormalities, Drug-Induced;Disease Models, Animal;Teratogens;Nervous System Malformations;Mice, Knockout;21 Neurophysiology;Methylazoxymethanol Acetate;Cerebral Cortex;Mice;24 Pubmed search results 2008;Rats, Mutant Strains}, Medline = {99329997}, Month = {7}, Nlm_Id = {2983306R}, Number = {7}, Organization = {INSERM U29, Paris, France.}, Pages = {811-21}, Pubmed = {10403203}, Title = {Cortical malformations and epilepsy: new insights from animal models}, Uuid = {8F7B0C48-015B-11DB-9E68-000D9346EC2A}, Volume = {40}, Year = {1999}, url = {papers/Chevassus-au-Louis_Epilepsia1999.pdf}} @article{Chevassus-au-Louis:1999a, Abstract = {Cortical heterotopia is defined as the misplacement of a group of neurons displaced to a precise localization in the neocortex and results from perturbed migration along the glial guide, either because of glial destruction or molecular anomalies. Heterotopic neurons are rarely dispersed but are rather grouped in nodules or bands. Heterotopic masses may lie in an ependymal or subcortical localization depending on whether they result from lack of migration or an arrested migration. Heterotopias can also occur in intra-cortical or extra-cortical localizations. The cause of heterotopia remains to be elucidated. Two genes situated on chromosome X have been implicated but non-genetic forms attributable to antenatal ischemia or toxic aggression during fetal development have also been observed. The presence of heterotopia is usually associated with epilepsy and sometimes with mental retardation. Seizures may be initiated within the heterotopic region then propagate via long projections to the neocortex which may also be malformed.}, Author = {Chevassus-au-Louis, N. and Robain, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0035-3787}, Journal = {Rev Neurol (Paris)}, Keywords = {Chromosomes, Human, Pair 10;Epilepsy;Cerebral Cortex;Brain Diseases;Neurons, Efferent;Chromosome Aberrations;21 Neurophysiology;21 Epilepsy;Chromosome Disorders;English Abstract;Choristoma;Neurons, Afferent;Humans;Animals;24 Pubmed search results 2008;Disease Models, Animal;review}, Medline = {99193810}, Month = {1}, Nlm_Id = {2984779R}, Number = {1}, Organization = {INSERM U29, Universit{\'e} Paris V Ren{\'e} Descartes, Paris.}, Pages = {51-8}, Pii = {MDOI-RN-01-1999-155-1-0035-3787-101019-ART38}, Pubmed = {10093850}, Title = {[Cortical heterotopias: animal models and human disease]}, Uuid = {1770AA54-A00E-4256-8CF8-7A1532300CF6}, Volume = {155}, Year = {1999}} @article{Cheynet:2006, Abstract = {The cellular HERV-W envelope/syncytin-1 protein, encoded by the envelope gene of the ERVWE1 proviral locus is a fusogenic glycoprotein probably involved in the formation of the placental syncytiotrophoblast layer. Syncytin-1-induced in vitro cell-cell fusion is dependent on the interaction with hASCT2. As no receptor binding domain has been clearly defined in the SU of neither the HERV-W Env nor the retroviruses of the same interference group, we designed an in vitro binding assay to evaluate the interaction of the HERV-W envelope with the hASCT2 receptor. Using truncated HERV-W SU subunits, a region consisting of the N-terminal 124 amino acids of the mature SU glycoprotein was determined as the minimal receptor-binding domain. This domain contains several sub-domains which are poorly conserved among retroviruses of this interference group but a region of 18 residus containing the SDGGGX2DX2R conserved motif was proved to be essential for syncytin-1-hASCT2 interaction.}, Author = {Cheynet, Val{\'e}rie and Oriol, Guy and Mallet, Fran\c{c}ois}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1742-4690}, Journal = {Retrovirology}, Keywords = {15 ERVs retroelements;Endogenous Retroviruses;Cell Fusion;Hela Cells;Gene Products, env;Cell Line;Amino Acid Transport System ASC;14 Immune;Receptors, Virus;15 Retrovirus mechanism;Humans;24 Pubmed search results 2008;Pregnancy Proteins}, Nlm_Id = {101216893}, Organization = {UMR 2714 CNRS-bioM{\'e}rieux, IFR128 BioSciences Lyon-Gerland, Ecole Normale Sup{\'e}rieure de Lyon, 69364 Lyon Cedex 07, France. valerie.cheynet\@ens-lyon.fr}, Pages = {41}, Pii = {1742-4690-3-41}, Pubmed = {16820059}, Title = {Identification of the hASCT2-binding domain of the Env ERVWE1/syncytin-1 fusogenic glycoprotein}, Uuid = {02106ACC-67D0-4A6B-9388-6A7209A24F08}, Volume = {3}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1742-4690-3-41}} @article{Chiasson:1999, Abstract = {The adult derivatives of the embryonic forebrain germinal zones consist of two morphologically distinct cell layers surrounding the lateral ventricles: the ependyma and the subependyma. Cell cycle analyses have revealed that at least two proliferating populations exist in this region, one that is constitutively proliferating and one that is relatively quiescent and thought to include the endogenous adult neural stem cells. Earlier studies demonstrated that specific dissection of the region surrounding the lateral ventricles was necessary for the in vitro isolation of multipotent, self-renewing neural stem cells. However, in these studies, the ependymal layer was not physically separated from the subependymal layer to identify the specific adult laminar localization of the neural stem cells around the lateral ventricles. To determine which cellular compartment in the adult forebrain contained the neural stem cells, we isolated and cultured the ependyma separately from the subependyma and tested for the presence of neural stem cells using the in vitro neurosphere assay. We demonstrate that the ependymal cells can proliferate in vitro to form sphere-like structures. However, the ependymal cells generating spheres do not have the ability to self-renew (proliferate to form secondary spheres after dissociation) nor to produce neurons, but rather only seem to generate glial fibrillary acidic protein-positive ependymal cells when plated under differentiation conditions in culture. On the other hand, a subpopulation of subependymal cells do possess the self-renewing and multipotential characteristics of neural stem cells. Therefore, the adult forebrain neural stem cell resides within the subependymal compartment.}, Author = {Chiasson, B. J. and Tropepe, V. and Morshead, C. M. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {J Neurosci}, Keywords = {02 Adult neurogenesis migration;Prosencephalon/*cytology/drug effects;Cerebral Ventricles/cytology/drug effects;Neurons/*cytology/drug effects;Comparative Study;B-14;Ependyma/*cytology/drug effects;Stem Cells/*cytology/drug effects;Cell Division/drug effects/physiology;Fibroblast Growth Factor, Basic/pharmacology;Animal;Nerve Growth Factors/pharmacology;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;Mice;Male}, Number = {11}, Organization = {Neurobiology Research Group, Department of Anatomy and Cell Biology, University of Toronto, Toronto, Canada, M5S 1A8.}, Pages = {4462-71.}, Title = {Adult mammalian forebrain ependymal and subependymal cells demonstrate proliferative potential, but only subependymal cells have neural stem cell characteristics}, Uuid = {C00389AC-EC80-11DA-8605-000D9346EC2A}, Volume = {19}, Year = {1999}, url = {papers/Chiasson_JNeurosci1999.pdf}} @article{Chih:2006, Abstract = {Formation of synapses requires specific cellular interactions that organize pre- and postsynaptic compartments. The neuroligin-neurexin complex mediates heterophilic adhesion and can trigger assembly of glutamatergic and GABAergic synapses in cultured hippocampal neurons. Both neuroligins and neurexins are encoded by multiple genes. Alternative splicing generates large numbers of isoforms, which may engage in selective axo-dendritic interactions. We explored whether alternative splicing of the postsynaptic neuroligins modifies their activity toward glutamatergic and GABAergic axons. We find that small extracellular splice insertions restrict the function of neuroligin-1 and -2 to glutamatergic and GABAergic contacts and alter interaction with presynaptic neurexins. The neuroligin isoforms associated with GABAergic contacts bind to neurexin-1alpha and a subset of neurexin-1betas. In turn, these neurexin isoforms induce GABAergic but not glutamatergic postsynaptic differentiation. Our findings suggest that alternative splicing plays a central role in regulating selective extracellular interactions through the neuroligin-neurexin complex at glutamatergic and GABAergic synapses.}, Author = {Chih, Ben and Gollan, Leora and Scheiffele, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Glycoproteins;Animals;Synapses;Cells, Cultured;Rats;comparative study;Alternative Splicing;Cercopithecus aethiops;COS Cells;Hippocampus;research support, non-u.s. gov't;Neuropeptides;21 Neurophysiology;Neurons;21 Activity-development;research support, n.i.h., extramural;24 Pubmed search results 2008;Membrane Proteins;Nerve Tissue Proteins}, Month = {7}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Physiology & Cellular Biophysics, Center for Neurobiology and Behavior, Columbia University Medical Center, College of Physicians & Surgeons, P&S 11-511, 630 West 168th Street, New York, New York 10032, USA.}, Pages = {171-8}, Pii = {S0896-6273(06)00458-2}, Pubmed = {16846852}, Title = {Alternative splicing controls selective trans-synaptic interactions of the neuroligin-neurexin complex}, Uuid = {A755CC2E-203C-48C4-84B4-92A78062591F}, Volume = {51}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.06.005}} @article{Chikada:1999, Abstract = {Gene therapy is a therapeutic strategy in treating cardiovascular disease. Vein graft failure, the major limitation on coronary artery bypass surgery, may be amenable to gene approaches. Some studies describe gene therapies using functioning genes to prevent vein graft stenosis. Gene transfer efficiency remains a major issue. In this rabbit vein graft model, we studied gene delivery using a replication-deficit recombinant adenovirus to improve gene transfer efficiency into vein grafts. The adenovirus vector that contains the E.coli lacZ gene encoding beta gal was used because this vector is widely used and thought to be effective. Gene transfer was detected by X-gal staining. We hypothesized that dimethylsulfoxide and hyaluronidase, both drug delivery enhancers, would improve efficiency and that, in transfer to adventitia, direct injection would be more effective than dwelling. We studied 3 gene delivery methods to intima and media (controls, using dimethylsulfoxide and using hyaluronidase before transfection) and 2 delivery methods to adventitia (direct injection and dwelling). We used 6 rabbits per delivery method. X-gal stained positive cell rates were counted using light microscopy. Our findings indicate that (1) dimethylsulfoxide increased the efficiency of transfection to media and intima, (2) hyaluronidase increased intimal transfection efficiency, (3) direct injection to adventitia was more effective than dwelling. These findings suggest that in vein grafting, our methods are feasible for improving gene transfer efficiency. 1344-4964 Journal Article}, Author = {Chikada, M. and Jones, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Jpn J Thorac Cardiovasc Surg}, Keywords = {Genetic Vectors;Gene Therapy/*methods;Graft Occlusion, Vascular/prevention &control;EE, DMSO, abstr;08 Aberrant cell cycle;Hyaluronoglucosaminidase;Transfection/*methods;Adenoviridae;Rabbits;Animals;Disease Models, Animal;Dimethyl Sulfoxide;Veins/*transplantation}, Number = {5}, Organization = {Department of Cardiovascular Surgery, National Children's Hospital, Tokyo, Japan.}, Pages = {204-9}, Pubmed = {10402767}, Title = {Study of gene delivery in a rabbit vein graft model. Improvement of the efficiency of gene transfer into vein grafts}, Uuid = {0992A834-9446-4397-B41D-35A118C2EF61}, Volume = {47}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10402767}} @article{Chittajallu:2002, Abstract = {Proliferative oligodendrocyte progenitor cells (OPs) express large, delayed outward-rectifying K(+) currents (I(K)), whereas nondividing immature and mature oligodendrocytes display much smaller I(K). Here, we show that up-regulation of I(K) occurs in G(1) phase of the cell cycle in purified cultured OPs and is the result of an RNA synthesis-dependent, selective increase of the K(+) channel subunit proteins Kv1.3 and Kv1.5. In oligodendrocyte cells acutely isolated from developing rat brain, a decrease of cyclin D expression is observed as these cells mature along their lineage. This is accompanied by a decrease in Kv1.3 and Kv1.5 subunit expression, suggesting a role for these subunits in the proliferative potential of OPs in situ. I(K) expressed in OPs in subventricular zone and developing white matter in acutely isolated slice preparations were selectively blocked by antagonists of Kv1.3, illustrating the functional presence of this subunit in situ. Interestingly, Kv1.3 block inhibited S-phase entry of both purified OPs in culture and in tissue slice cultures. Thus, we employ both in vitro and in situ experimental approaches to show that (i) RNA-dependent synthesis of Kv1.3 and Kv1.5 subunit proteins occurs in G(1) phase of the OP cell cycle and is responsible for the observed increase in I(K), and (ii) currents through Kv1.3-containing channels play a crucial role in G(1)/S transition of proliferating OPs. 0027-8424 Journal Article}, Author = {Chittajallu, R. and Chen, Y. and Wang, H. and Yuan, X. and Ghiani, C. A. and Heckman, T. and McBain, C. J. and Gallo, V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Human;Electrophysiology;Animals;Cells, Cultured;Up-Regulation;Rats;*G1 Phase;Rats, Sprague-Dawley;11 Glia;G abstr;Oligodendroglia/*cytology/metabolism;Time Factors;Dimerization;Support, Non-U.S. Gov't;Cell Lineage;Blotting, Western;Brain/embryology/metabolism/physiology;Lysine/*analogs &derivatives/metabolism;Cell Division;Cyclins/biosynthesis;Immunohistochemistry;*S Phase;Potassium Channels/*biosynthesis;Platelet-Derived Growth Factor/metabolism;RNA/metabolism}, Number = {4}, Organization = {Laboratory of Cellular and Synaptic Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4495, USA.}, Pages = {2350-5}, Pubmed = {11854528}, Title = {Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle}, Uuid = {8B0AB717-A368-4304-B620-61D9316F8005}, Volume = {99}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11854528}} @article{Chiu:1996, Abstract = {Several lines of evidence suggest an important role for glia in establishing boundaries during development of mammalian cortex and insect olfactory lobe. In the adult rat olfactory bulb distinct morphological categories of astroglial cells with clear laminar specificity are easily recognized following immunocytochemical staining of glial fibrillary acidic protein (GFAP). To explore the developmental distribution of olfactory bulb astrocytes and their possible role in establishing the segregation of neurons in specific olfactory bulb laminae, we used immunocytochemical localization of GFAP in rats at 0, 6, 9, 12, 15 and 21 days postnatal plus the adult. In the adult we confirmed prior observations and identified five morphological categories of astrocytes: linear, wedge, elongate, semicircular, and circular. Each category had a unique sublaminar distribution across the olfactory bulb, although categories could occur in more than one lamina. Between 0 and 21 days postnatal a 6th category was apparent, radial glial cells. The mature astrocyte morphologies did not emerge uniformly. Astrocytes found in the outermost glomerular layer developed first with the appearance of the linear, wedge and elongate morphologies. Deeper laminate of the olfactory bulb followed in a successive fashion until the adult pattern was evident around 15 days postnatal. As radial glia disappeared, the mature morphologies assumed their final position. The data suggest that the maturation of olfactory bulb astrocytes may be linked to the final migration and maturation of olfactory bulb neurons.}, Author = {Chiu, K. and Greer, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Glial Fibrillary Acidic Protein/metabolism;Rats, Sprague-Dawley;G abstr;Immunohistochemistry;Rats;Animals, Newborn/physiology;Animal;11 Glia;Support, U.S. Gov't, P.H.S.;Olfactory Bulb/*cytology/*growth &development/metabolism;Astrocytes/metabolism/*physiology/ultrastructure}, Number = {1}, Organization = {Section of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA.}, Pages = {28-37.}, Title = {Immunocytochemical analyses of astrocyte development in the olfactory bulb}, Uuid = {720A4690-540F-457D-A195-166571380D9F}, Volume = {95}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8873973}} @article{Chmielnicki:2004, Abstract = {Neurogenesis from endogenous progenitor cells in the adult forebrain ventricular wall may be induced by the local viral overexpression of cognate neuronal differentiation agents, in particular BDNF. Here, we show that the overexpression of noggin, by acting to inhibit glial differentiation by subependymal progenitor cells, can potentiate adenoviral BDNF-mediated recruitment of new neurons to the adult rat neostriatum. The new neurons survive at least 2 months after their genesis in the subependymal zone and are recruited primarily as GABAergic DARPP-32+ medium spiny neurons in the caudate-putamen. The new medium spiny neurons successfully project to the globus pallidus, their usual developmental target, extending processes over several millimeters of the normal adult striatum. Thus, concurrent suppression of subependymal glial differentiation and promotion of neuronal differentiation can mobilize endogenous subependymal progenitor cells to achieve substantial neuronal addition to otherwise non-neurogenic regions of the adult brain. 1529-2401 Journal Article}, Author = {Chmielnicki, E. and Benraiss, A. and Economides, A. N. and Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {J Neurosci}, Keywords = {C pdf;04 Adult neurogenesis factors}, Number = {9}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.}, Pages = {2133-42}, Title = {Adenovirally expressed noggin and brain-derived neurotrophic factor cooperate to induce new medium spiny neurons from resident progenitor cells in the adult striatal ventricular zone}, Uuid = {602A11ED-D3D4-4BA0-82A3-EDF31E266AA6}, Volume = {24}, Year = {2004}, url = {papers/Chmielnicki_JNeurosci2004.pdf}} @article{Cho:2003, Abstract = {Transection of the medial forebrain bundle caused apoptosis of dopamine neurons in the rat substantia nigra. Immunohistochemical localization of activated microglia and tyrosine hydroxylase in the axotomized substantia nigra showed that activation of microglia was rapid and OX-6 (MHC-II marker)-positive and ED1 (lysosomal phagocytic marker)-positive microglia were apposed to structurally intact tyrosine hydroxylase-positive dopamine neurons, indicating microglial phagocytosis of degenerating dopamine neurons. The occurrence of microglial phagocytosis at early stages of apoptosis may indicate the evolution of apoptosis into an irreversible state. Alternatively, interventions that suppress early activation of microglia might lead to novel mechanisms for neuron protection.}, Author = {Cho, Byung Pil and Sugama, Shuei and Shin, Dong Hoon and DeGiorgio, Lorraine A. and Kim, Sung Soo and Kim, Yoon Seong and Lim, So Young and Park, Key Chung and Volpe, Bruce T. and Cho, Sunghee and Joh, Tong H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0272-4340}, Journal = {Cell Mol Neurobiol}, Keywords = {Dopamine;Nerve Degeneration;Animals;Phagocytosis;Rats;Medial Forebrain Bundle;Apoptosis;Microglia;Reaction Time;Substantia Nigra;Rats, Wistar;Not relevant;11 Glia;Male;Neurons;Axotomy;Tyrosine 3-Monooxygenase;Biological Markers;Membrane Proteins;Histocompatibility Antigens Class II}, Medline = {22875838}, Month = {10}, Nlm_Id = {8200709}, Number = {4-5}, Organization = {The Burke Medical Research Institute, Department of Neurology and Neuroscience, Weill Medical College, Graduate School of Medical Sciences of Cornell University, White Plains, New York 10605, USA.}, Pages = {551-60}, Pubmed = {14514015}, Title = {Microglial phagocytosis of dopamine neurons at early phases of apoptosis}, Uuid = {4916D88B-13F5-4847-8B85-07B3D6678D21}, Volume = {23}, Year = {2003}} @article{Choi:2003, Abstract = {AIMS/HYPOTHESIS: Bone marrow cells contain at least two distinct types of stem cells which are haematopoietic stem cells and mesenchymal stem cells. Both cells have the ability to differentiate into a variety of cell types derived from all three germ layers. Thus, bone marrow stem cells could possibly be used to generate new pancreatic beta cells for the treatment of diabetes. In this study, we investigated the feasibility of bone marrow-derived cells to differentiate into beta cells in pancreas. METHODS: Using green fluorescent protein transgenic mice as donors, the distribution of haematogenous cells in the pancreas was studied after bone marrow transplantation. RESULTS: In the pancreas of green fluorescent protein chimeric mice, green fluorescent protein-positive cells were found in the islets, but none of these cells expressed insulin. Previous data has suggested that tissue injury can recruit haematopoietic stem cells or their progeny to a non-haematopietic cell fate. Therefore, low-dose streptozotocin (30 or 50 mg/kg on five consecutive days) was injected into the mice 5 weeks after bone marrow transplantation, but no green fluorescent protein-positive cells expressing insulin were seen in the islets or around the ducts of the pancreas. CONCLUSIONS/INTERPRETATION: Our data suggests that bone marrow-derived cells are a distinct cell population from islet cells and that transdifferentiation from bone marrow-derived cells to pancreatic beta cells is rarely observed.}, Author = {Choi, J. B. and Uchino, H. and Azuma, K. and Iwashita, N. and Tanaka, Y. and Mochizuki, H. and Migita, M. and Shimada, T. and Kawamori, R. and Watada, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0012-186X}, Journal = {Diabetologia}, Keywords = {Indicators and Reagents;Cell Differentiation;Research Support, Non-U.S. Gov't;Luminescent Proteins;Chimera;Bone Marrow Cells;Streptozocin;Islets of Langerhans;Bone Marrow Transplantation;11 Glia;Mice, Transgenic;Pancreas;Insulin;Green Fluorescent Proteins;Mice;Animals;Feasibility Studies}, Medline = {22892238}, Month = {10}, Nlm_Id = {0006777}, Number = {10}, Organization = {Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.}, Pages = {1366-74}, Pubmed = {12898006}, Title = {Little evidence of transdifferentiation of bone marrow-derived cells into pancreatic beta cells}, Uuid = {BACB0482-2E63-46D3-A64B-050727B8FFA6}, Volume = {46}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00125-003-1182-9}} @article{Choi:2003a, Abstract = {The present study examined whether thrombin-induced microglial activation could contribute to death of dopaminergic neurons in the rat substantia nigra (SN) in vivo. Seven days after thrombin injection into the SN, tyrosine hydroxylase immunohistochemistry showed a significant loss of nigral dopaminergic neurons. In parallel, thrombin-activated microglia, visualized by immunohistochemical staining using antibodies against the complement receptor type 3 (OX-42) and the major histocompatibility complex class II antigens were also observed in the SN, where degeneration of nigral neurons was found. Reverse transcription PCR at various time points demonstrated that activated microglia in vivo exhibited an early and transient expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and several proinflammatory cytokines, including interleukin 1beta (IL-1beta), IL-6, and tumor necrosis factor alpha. Western blot analysis and double-label immunohistochemistry showed an increase in the expression of iNOS and COX-2 and the colocalization of these proteins within microglia. The thrombin-induced loss of SN dopaminergic neurons was partially inhibited by NG-nitro-L-arginine methyl ester hydrochloride, an NOS inhibitor, and by DuP-697, a COX-2 inhibitor. Additional studies demonstrated that extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 mitogen-activated protein kinase (MAPK) were activated in the SN as early as 30 min after thrombin injection, and that these kinases were localized within microglia. Inhibition of ERK1/2 and p38 MAPK reduced iNOS and COX-2 mRNA expression and rescued dopaminergic neurons in the SN. The present results strongly suggest that microglial activation triggered by endogenous compound(s) such as thrombin may be involved in the neuropathological processes of dopaminergic neuronal cell death that occur in Parkinson's disease.}, Author = {Choi, Sang-H H. and Joe, Eun H. and Kim, Seung U. and Jin, Byung K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Prostaglandin-Endoperoxide Synthase;Dopamine;Animals;Disease Progression;Stereotaxic Techniques;Microinjections;Rats;Enzyme Inhibitors;07 Excitotoxicity Apoptosis;Microglia;Female;Cell Count;Nitric-Oxide Synthase;Rats, Sprague-Dawley;Substantia Nigra;Not relevant;11 Glia;Support, Non-U.S. Gov't;Neurons;Thrombin;Tyrosine 3-Monooxygenase;Parkinsonian Disorders;Immunohistochemistry;Isoenzymes;Mitogen-Activated Protein Kinases;Cytokines}, Medline = {22727329}, Month = {7}, Nlm_Id = {8102140}, Number = {13}, Organization = {Brain Disease Research Center, Neuroscience Graduate Program, Ajou University School of Medicine, Suwon 442-749, Korea.}, Pages = {5877-86}, Pii = {23/13/5877}, Pubmed = {12843292}, Title = {Thrombin-induced microglial activation produces degeneration of nigral dopaminergic neurons in vivo}, Uuid = {CD6E53EB-9EE0-4988-AEBC-A1E9A802B3E6}, Volume = {23}, Year = {2003}, url = {papers/Choi_JNeurosci2003}} @article{Choi:2005, Abstract = {To better understand the pathophysiological role of Src protein, a non-receptor protein tyrosine kinase of 60kDa, in the ischemic brain, we investigated the time course and regional distribution of active Src expression by using a specific antibody against Tyr416 phosphorylated Src (phospho-Src) in the rat hippocampus after transient forebrain ischemia. In the hippocampus of the control animals, active Src expression was too low to be detected by immunolabeling. Beginning 4h after reperfusion, active Src expression became evident and, after 1 day, had increased preferentially in the CA field of the hippocampus proper and the dentate gyrus. By day 3, active Src expression markedly increased in the pyramidal cell layer of CA1 and the dentate hilar region in temporal correlation with neuronal cell death occurring in these areas, where cells typical of phagocytic microglia showed phospho-Src immunoreactivity. Double-labeling experiments revealed that cells expressing active Src were microglia that stained for biotinylated lectin derived from Griffonia simplicifolia (GSI-B4). Active Src expression began to decline at day 7 and returned to the basal level by day 14 after reperfusion. These results demonstrate increased phosphorylation of Src in activated microglia of the post-ischemic hippocampus, indicating that Src signaling may be involved in the microglial reaction to an ischemic insult.}, Author = {Choi, Jeong-Sun S. and Kim, Ha-Young Y. and Chung, Jin-Woong W. and Chun, Myung-Hoon H. and Kim, Seong Yun and Yoon, Shin-Hee H. and Lee, Mun-Yong Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Animals;Rats;Comparative Study;src-Family Kinases;Microglia;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Gene Expression Regulation, Enzymologic;11 Glia;Time Factors;Disease Models, Animal;Male;Antigens;Immunohistochemistry;Ischemic Attack, Transient;Lectins;Research Support, Non-U.S. Gov't}, Nlm_Id = {7600130}, Number = {1-2}, Organization = {Department of Anatomy, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Socho-gu, Seoul 137-701, Korea.}, Pages = {1-5}, Pii = {S0304-3940(05)00029-7}, Pubmed = {15854740}, Title = {Activation of Src tyrosine kinase in microglia in the rat hippocampus following transient forebrain ischemia}, Uuid = {144F8DED-B473-4749-8A8B-6C154CD8A590}, Volume = {380}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2005.01.015}} @article{Chow:2000, Abstract = {We analyze the existence and stability of phase-locked states of neurons coupled electrically with gap junctions. We show that spike shape and size, along with driving current (which affects network frequency), play a large role in which phase-locked modes exist and are stable. Our theory makes predictions about biophysical models using spikes of different shapes, and we present simulations to confirm the predictions. We also analyze a large system of all-to-all coupled neurons and show that the splay-phase state can exist only for a certain range of frequencies.}, Author = {Chow, C. C. and Kopell, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0899-7667}, Journal = {Neural Comput}, Keywords = {Synapses;20 Networks;Gap Junctions;Electric Conductivity;research support, non-u.s. gov't;21 Neurophysiology;Action Potentials;Models, Neurological;Computer Simulation;research support, u.s. gov't, non-p.h.s.;Interneurons;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {9426182}, Number = {7}, Organization = {Department of Mathematics, University of Pittsburgh, PA 15206, USA.}, Pages = {1643-78}, Pubmed = {10935921}, Title = {Dynamics of spiking neurons with electrical coupling}, Uuid = {DEAE86BA-5E13-4662-8E41-499E5BFCA5AE}, Volume = {12}, Year = {2000}, url = {papers/Chow_NeuralComput2000.pdf}} @article{Chrobak:1998, Abstract = {How do ensembles of neurons distributed across the hippocampal and entorhinal cortices effectively interact? In the awake-behaving rat, specific subpopulations of hippocampal and entorhinal neurons become entrained into two prominent fast-frequency rhythms (gamma [40-100 Hz], and 200 Hz). These fast rhythms are coupled to slower synchronizing potentials (theta and sharp wave, respectively), are correlated to macroscopic behavioral states, and to some extent are anatomically distinct. These population dynamics allow distributed populations of neurons across the hippocampal and entorhinal cortices to discharge together in time on the order of tens of milliseconds, and thus allow interconnected domains of a distributed neural network to become transiently entraining into synchronized, fast-frequency, population ensembles. We believe that these transient population dynamics allow interconnected domains to "effectively communicate"and modify their synaptic connectivity. 0149-7634 Journal Article Review Review, Tutorial}, Author = {Chrobak, J. J. and Buzsaki, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Neurosci Biobehav Rev}, Keywords = {18 Classic Neuroanatomy Physiology;Neurons/*physiology;Theta Rhythm;Behavior, Animal/physiology;Hippocampus/cytology/*physiology;Human;Rats;M;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Behavior;Animals;Support, Non-U.S. Gov't;Entorhinal Cortex/cytology/*physiology}, Number = {2}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers-State University of New Jersey, Newark 07102, USA.}, Pages = {303-10}, Pubmed = {9579320}, Title = {Operational dynamics in the hippocampal-entorhinal axis}, Uuid = {EF1D475A-1BD4-4050-B87A-179DA6B22F2F}, Volume = {22}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9579320}} @article{Chuang:2007, Abstract = {Gap junctions are widespread in immature neuronal circuits, but their functional significance is poorly understood. We show here that a transient network formed by the innexin gap-junction protein NSY-5 coordinates left-right asymmetry in the developing nervous system of Caenorhabditis elegans. nsy-5 is required for the left and right AWC olfactory neurons to establish stochastic, asymmetric patterns of gene expression during embryogenesis. nsy-5-dependent gap junctions in the embryo transiently connect the AWC cell bodies with those of numerous other neurons. Both AWCs and several other classes of nsy-5-expressing neurons participate in signaling that coordinates left-right AWC asymmetry. The right AWC can respond to nsy-5 directly, but the left AWC requires nsy-5 function in multiple cells of the network. NSY-5 forms hemichannels and intercellular gap-junction channels in Xenopus oocytes, consistent with a combination of cell-intrinsic and network functions. These results provide insight into gap-junction activity in developing circuits.}, Author = {Chuang, Chiou-Fen F. and Vanhoven, Miri K. and Fetter, Richard D. and Verselis, Vytas K. and Bargmann, Cornelia I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-05-30 19:05:45 +0000}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008; mirror symmetry; patterning; Gap Junctions; gene}, Month = {5}, Nlm_Id = {0413066}, Number = {4}, Organization = {Howard Hughes Medical Institute, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.}, Pages = {787-99}, Pii = {S0092-8674(07)00451-5}, Pubmed = {17512411}, Title = {An Innexin-Dependent Cell Network Establishes Left-Right Neuronal Asymmetry in C. elegans}, Uuid = {61DBB00B-304D-42C7-9712-9B9038F8D11D}, Volume = {129}, Year = {2007}, url = {papers/Chuang_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2007.02.052}} @article{Chudotvorova:2005, Abstract = {The development of GABAergic synapses is associated with an excitatory to inhibitory shift of the actions of GABA because of a reduction of [Cl-]i. This is due to a delayed postnatal expression of the K+ -Cl- cotransporter KCC2, which has low levels at birth and peaks during the first few postnatal weeks. Whether the expression of the cotransporter and the excitatory to inhibitory shift have other consequences on the operation of GABA(A) receptors and synapses is not yet known. We have now expressed KCC2 in immature neurones at an early developmental stage and determined the consequences on the formation of GABA and glutamate synapses. We report that early expression of the cotransporter selectively enhances GABAergic synapses: there is a significant increase of the density of GABA(A) receptors and synapses and an increase of the frequency of GABAergic miniature postsynaptic currents. The density of glutamate synapses and frequency of AMPA miniature postsynaptic currents are not affected. We conclude that the expression of KCC2 and the reduction of [Cl-]i play a critical role in the construction of GABAergic networks that extends beyond the excitatory to inhibitory shift of the actions of GABA.}, Author = {Chudotvorova, Ilona and Ivanov, Anton and Rama, Sylvain and H{\"u}bner, Christian A. and Pellegrino, Christophe and Ben-Ari, Yehezkel and Medina, Igor}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Animals;Synapses;Gene Expression Regulation, Developmental;21 Epilepsy;21 Neurophysiology;Action Potentials;Rats;Hippocampus;Recombinant Proteins;Rats, Wistar;Animals, Newborn;gamma-Aminobutyric Acid;Cells, Cultured;Symporters;24 Pubmed search results 2008;Tissue Culture Techniques;Neurons}, Month = {8}, Nlm_Id = {0266262}, Number = {Pt 3}, Organization = {INMED/INSERM Unite 29, 163 Route de Luminy, 13009 Marseille, France.}, Pages = {671-9}, Pii = {jphysiol.2005.089821}, Pubmed = {15961425}, Title = {Early expression of KCC2 in rat hippocampal cultures augments expression of functional GABA synapses}, Uuid = {DC035323-3DB2-4679-9E5B-9AB3E0B18142}, Volume = {566}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2005.089821}} @article{Chugani:1991, Abstract = {The developmental appearance of ameboid and ramified microglia in the rat brain has been examined by immunofluorescent localization of vaults, recently described ribonucleoprotein particles (Kedersha and Rome, 1986a). Vaults are distinct, multiarched structures of unknown function expressed by higher and lower eukaryotic species. Although vaults have been detected in all mammalian cells examined to date, they are highly enriched in macrophages. In the brain, vault antisera is highly specific for both ameboid and ramified microglia. The developmental profile of vault immunoreactivity in rat brain slices suggests that microglia enter the brain at 2 locations, with different time scales for each. The first migration, which begins before embryonic day 15 and subsides between postnatal days 7 and 14, was identified by vault immunoreactivity and Bandeiraea simplicifolia B4-isolectin (a microglia marker) staining. The cells appear to enter from blood vessels and display a ramified morphology as soon as they are detected in the brain. The second microglial migration occurs in the first postnatal week, when ameboid microglia appear in the corpus callosum and other large fiber tracts. Ameboid microglia appear to differentiate into ramified microglia between postnatal days 4 and 14. Vault immunoreactivity, as a very early microglial marker, provides new insight regarding the much-debated origin of the ramified microglia. It is quite clear that ameboid cells are not the sole source of ramified microglia because ramified cells can be detected before the influx of ameboid microglia. Colocalization studies with monocyte/macrophage markers ED1 and OX42 demonstrate that both ramified and ameboid microglia originate from monocyte lineage.}, Author = {Chugani, D. C. and Kedersha, N. L. and Rome, L. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Aging;Cells, Cultured;Embryo;Neuroglia;Rats;Not relevant;11 Glia;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Mesoderm;Fluorescent Antibody Technique;Animals;Brain;Immune Sera;Macrophages;Organelles}, Medline = {91093747}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Department of Radiological Sciences, UCLA School of Medicine 90024.}, Pages = {256-68}, Pubmed = {1986066}, Title = {Vault immunofluorescence in the brain: new insights regarding the origin of microglia}, Uuid = {4FF36366-73EF-4915-A2A7-E731849C9193}, Volume = {11}, Year = {1991}} @article{Churchill:2004, Abstract = {BACKGROUND: Topographic reorganization of central maps following peripheral nerve injury has been well characterized. Despite extensive documentation of these physiological changes, the underlying anatomical correlates have yet to be fully explored. In this study, we used Golgi impregnation and light microscopy to assess dendritic morphology following denervation of the glabrous hand surface in adult primates. RESULTS: After survival durations that permit complete physiologically-defined reorganization, we find a systematic change in the dendritic arborization pattern of both layer II/III pyramidal and layer IV spiny stellate cells in the contralateral hand region of area 3b, compared to unaffected cortical areas. In general, our analyses indicate a progressive expansion of distal regions of the dendritic arbor with no appreciable changes proximally. This pattern of distal dendritic elaboration occurs for both basilar and apical dendrites. CONCLUSIONS: These observations are consistent with the notion that latent inputs gain expression in reorganized cortex after nerve injury via their influence through contacts with more distally located termination sites.}, Author = {Churchill, James D. and Tharp, Jason A. and Wellman, Cara L. and Sengelaub, Dale R. and Garraghty, Preston E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1471-2202}, Journal = {BMC Neurosci}, Keywords = {10 Development;11 Glia;10 Structural plasticity;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {100966986}, Number = {1}, Organization = {Department of Psychology, Saint Louis University, St. Louis, Missouri 63103, USA. churchj\@slu.edu }, Pages = {43}, Pii = {1471-2202-5-43}, Pubmed = {15533258}, Title = {Morphological correlates of injury-induced reorganization in primate somatosensory cortex}, Uuid = {15E6B9EF-0927-4FAE-AD91-444456C0CD6C}, Volume = {5}, Year = {2004}, url = {papers/Churchill_BMCNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1471-2202-5-43}} @article{Ciaroni:1999, Abstract = {Neurogenesis occurs throughout adult life in rat dentate gyrus. Factors and mechanisms of adult neurogenesis regulation are not well known. Vitamin E deficiency has been found to deliver a neurogenetic potential in rat dorsal root ganglia. To determine whether the role of tocopherols in adult neurogenesis may be generalized to the central nervous system, changes in adult rat dentate gyrus neurogenesis were investigated in vitamin E deficiency. Neurogenesis was quantitatively studied by determination of the density of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells and by determination of the total number of cells in the granule cell layer. The BrdU-labeled cells were immunocytochemically characterized by demonstration of neuronal marker calbindin D28K. The following results were found: (1) the volume of the granule layer increased in controls from 1 to 5 months of age, mainly due to cell density decrease; (2) the volume increased by a similar amount in vitamin E-deficient rats, mainly because of an increase in cell number; (3) BrdU-positive cells were more numerous in vitamin E- deficient rats in comparison to age-matched controls; (4) the increase in proliferated cells was located in the hilus and in the plexiform layer. This study confirms that neurogenesis occurs within adult dentate gyrus and demonstrates that this process is enhanced in vitamin E deficiency. This finding indicates that vitamin E may be an exogenous factor regulating adult neurogenesis.}, Author = {Ciaroni, S. and Cuppini, R. and Cecchini, T. and Ferri, P. and Ambrogini, P. and Cuppini, C. and Del Grande, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Comp Neurol}, Keywords = {Rats, Sprague-Dawley;C-12;Rats/*anatomy &histology;Cell Division;Cell Count;Animal;Vitamin E Deficiency/*pathology;DNA Replication;04 Adult neurogenesis factors;Male;Neurons/*pathology;Dentate Gyrus/*pathology}, Number = {3}, Organization = {Istituto di Scienze Morfologiche, University of Urbino, I-61029 Urbino, Italy. s.ciaroni\@uniurb.it}, Pages = {495-502.}, Title = {Neurogenesis in the adult rat dentate gyrus is enhanced by vitamin E deficiency}, Uuid = {E46723EB-6EF3-424B-8414-F8D8D533A99F}, Volume = {411}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10413782}} @article{Ciaroni:2002, Abstract = {In order to investigate the role of postnatal neurogenesis in granule cell number control in the rat dentate gyrus, we administered Methylazoxymethanol (MAM), a drug able to prevent cells from dividing, on P3, P5, P7, P9, when the most granule cells are produced. The effect of MAM on the number of proliferating precursors and of granule cells was examined at P16 and P90. We used 5-bromo-2'-deoxyuridine administration to label proliferating cells and immunohistochemistry to characterize the cell phenotype using neuron markers TUC 4, PSA-NCAM, Calbindin D28K and glial marker GFAP. At 16 days of age in MAM-treated rats we observed a significant decrease of BrdU-positive cells. Consistently, a decrease in density and number of granule cells was found compared to the controls. At 90 days the dentate gyrus of treated rats showed a complete recovery: no differences in the density, total number of neurons, the BrdU- and TUC 4-positive cells were revealed with respect to the controls. No deficits were evident in performance on the water maze in MAM-treated rats. These data suggest that the dentate gyrus is able to re-establish the proliferative zone and to rebuild the granule cell layer following neonatal MAM administration.}, Author = {Ciaroni, S. and Cecchini, T. and Ferri, P. and Ambrogini, P. and Cuppini, R. and Lombardelli, G. and Peruzzi, G. and Del Grande, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Journal = {Mech Ageing Dev}, Keywords = {D;06 Adult neurogenesis injury induced}, Number = {5}, Organization = {Institute of Morphological Sciences, University of Urbino, loc. Crocicchia, I-61029 (PS), Urbino, Italy}, Pages = {499-509.}, Title = {Postnatal development of rat dentate gyrus: effects of methylazoxymethanol administration}, Uuid = {DA923AC9-6C2B-4C62-BB2B-7A10E8B1A3B1}, Volume = {123}, Year = {2002}, url = {papers/Ciaroni_MechAgeingDev2002}} @article{Cina:2007, Abstract = {During embryonic development, young neurons migrate from the ventricular zone to the cortical plate of the cerebral cortex. Disturbances in this neuronal migration have been associated with numerous diseases such as mental retardation, double cortex, Down syndrome, and epilepsy. One possible cause of these neuropathologies is an aberration in normal gap junctional communication. At least 20 connexin (Cx) genes encode gap junction proteins in mice and humans. A proper understanding of the role of specific connexins in the developing brain requires the characterization of their spatial and temporal pattern of expression. In the current study we performed all the experiments on mouse developing cortex at embryonic days (E) 14, 16, and 18, timepoints that are highly active with regard to cortical development. Using reverse transcription-polymerase chain reaction, Western blot analysis, and immunohistochemistry, we found that among the family of gap junction proteins, Cx26, Cx36, Cx37, Cx43, and Cx45 were expressed in the developing cortex of mice, Cx30 and Cx32 were absent, while Cx40 was expressed at a very low level. Our results demonstrate that Cx26 and Cx37 were evenly distributed in the cortical layers of developing brain, while Cx36 and Cx43 were more abundant in the ventricular zone and cortical plate. Cx45 distribution appeared to be more abundant at E18 compared to the other timepoints (E14 and E16). Thus, the present study provides identification and the distribution pattern for Cxs associated with cortical development during normal neuronal migration.}, Author = {Cina, Cima and Bechberger, John F. and Ozog, Mark A. and Naus, Christian C. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Microtubule-Associated Proteins;Neurons;Gene Expression Regulation, Developmental;research support, non-u.s. gov't;Tissue Distribution;21 Neurophysiology;Mice, Inbred C57BL;Neocortex;Gene Expression Profiling;21 Gap junctions;Animals;Cell Movement;24 Pubmed search results 2008;Connexins;Mice}, Month = {9}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Cellular & Physiological Sciences, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada.}, Pages = {298-313}, Pubmed = {17640036}, Title = {Expression of connexins in embryonic mouse neocortical development}, Uuid = {B3980DC4-D251-48E0-BC45-F5114892128D}, Volume = {504}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21426}} @article{Cirelli:2006, Abstract = {Long-term sleep deprivation in rats produces dramatic physiological changes including increase in energy expenditure, decrease in body weight, and death after 2-3 weeks. Despite several studies, the sleep deprivation syndrome remains largely unexplained. Here, to elucidate how prolonged sleep loss affects brain cells we used microarrays and screened the expression of > 26 000 transcripts in the cerebral cortex. Rats were sleep deprived using the disk-over-water method for 1 week. Seventy-five transcripts showed increased expression in these animals relative to controls that had been spontaneously awake or sleep deprived for a few hours. Most of them were induced as a result of chronic sleep loss and not non-specific effects of the disk stimulation. They include transcripts coding for several immunoglobulins, stress response proteins (macrophage inhibitor factor-related protein 14, heat-shock protein 27, alpha-B-crystallin), minoxidil sulfotransferase, globins and cortistatin. Twenty-eight transcripts decreased their expression in long-term sleep-deprived rats. Sixteen of them were specifically decreased as a result of chronic sleep loss, including those coding for type I procollagen and dihydrolipoamide acetyltransferase. We also compared sleeping rats to short-term and long-term sleep-deprived rats, and found that acute and chronic sleep loss led to some differences at the molecular level. Several plasticity-related genes were strongly induced after acute sleep deprivation only, and several glial genes were down-regulated in both sleep deprivation conditions, but to a different extent. These findings suggest that sustained sleep loss may trigger a generalized inflammatory and stress response in the brain.}, Author = {Cirelli, Chiara and Faraguna, Ugo and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Electroencephalography;Behavior, Animal;21 Neurophysiology;Sleep Deprivation;Rats;Wakefulness;Gene Expression Regulation;Time Factors;Gene Expression;comparative study;research support, n.i.h., extramural;Rats, Inbred WKY;Animals;Brain;Male;Microarray Analysis;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {2985190R}, Number = {5}, Organization = {Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719, USA. ccirelli\@wisc.edu}, Pages = {1632-45}, Pii = {JNC4058}, Pubmed = {16923172}, Title = {Changes in brain gene expression after long-term sleep deprivation}, Uuid = {8036B6CD-B3C8-49E9-A2A6-9A06DB31A7B9}, Volume = {98}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1471-4159.2006.04058.x}} @article{Cirelli:2005, Abstract = {Sleep intensity is regulated by the duration of previous wakefulness, suggesting that waking results in the progressive accumulation of sleep need (Borbely and Achermann, 2000). In mammals, sleep intensity is reflected by slow-wave activity (SWA) in the nonrapid eye movement (NREM) sleep electroencephalogram, which increases in proportion to the time spent awake. However, the mechanisms responsible for the increase of NREM SWA after wakefulness remain unclear. According to a recent hypothesis (Tononi and Cirelli, 2003), the increase in SWA occurs because during wakefulness, many cortical circuits undergo synaptic potentiation, as evidenced by the widespread induction of long-term potentiation (LTP)-related genes in the brain of awake animals. A direct prediction of this hypothesis is that manipulations interfering with the induction of LTP-related genes should result in a blunted SWA response. Here, we examined SWA response in rats in which cortical norepinephrine (NA) was depleted, a manipulation that greatly reduces the induction of LTP-related genes during wakefulness (Cirelli and Tononi, 2004). We found that the homeostatic response of the lower-range SWA was markedly and specifically reduced after NA depletion. These data suggest that the wake-dependent accumulation of sleep need is causally related to cellular changes dependent on NA release, such as the induction of LTP-related genes, and support the hypothesis that sleep SWA homeostasis may be related to synaptic potentiation during wakefulness.}, Author = {Cirelli, Chiara and Huber, Reto and Gopalakrishnan, Anupama and Southard, Teresa L. and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Sleep Disorders;Wakefulness;Dopamine;Serotonin Uptake Inhibitors;Animals;Rats;comparative study;Locus Coeruleus;Norepinephrine;Brain;Homeostasis;Sleep Stages;Rats, Inbred WKY;Behavior, Animal;Time Factors;Analysis of Variance;Male;Brain Chemistry;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Fluoxetine;24 Pubmed search results 2008;Drug Interactions;Benzylamines;Electroencephalography;Serotonin;Spectrum Analysis}, Month = {5}, Nlm_Id = {8102140}, Number = {18}, Organization = {Department of Psychiatry, University of Wisconsin, Madison, Madison, Wisconsin 53719, USA. ccirelli\@wisc.edu}, Pages = {4503-11}, Pii = {25/18/4503}, Pubmed = {15872097}, Title = {Locus ceruleus control of slow-wave homeostasis}, Uuid = {8DA33894-2A46-4182-9C7C-2638791AF4EE}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4845-04.2005}} @article{Cirelli:2005a, Abstract = {Most of us sleep 7-8 h per night, and if we are deprived of sleep our performance suffers greatly; however, a few do well with just 3-4 h of sleep-a trait that seems to run in families. Determining which genes underlie this phenotype could shed light on the mechanisms and functions of sleep. To do so, we performed mutagenesis in Drosophila melanogaster, because flies also sleep for many hours and, when sleep deprived, show sleep rebound and performance impairments. By screening 9,000 mutant lines, we found minisleep (mns), a line that sleeps for one-third of the wild-type amount. We show that mns flies perform normally in a number of tasks, have preserved sleep homeostasis, but are not impaired by sleep deprivation. We then show that mns flies carry a point mutation in a conserved domain of the Shaker gene. Moreover, after crossing out genetic modifiers accumulated over many generations, other Shaker alleles also become short sleepers and fail to complement the mns phenotype. Finally, we show that short-sleeping Shaker flies have a reduced lifespan. Shaker, which encodes a voltage-dependent potassium channel controlling membrane repolarization and transmitter release, may thus regulate sleep need or efficiency.}, Author = {Cirelli, Chiara and Bushey, Daniel and Hill, Sean and Huber, Reto and Kreber, Robert and Ganetzky, Barry and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:19 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Protein Structure, Tertiary;24 Pubmed search results 2008;Circadian Rhythm;Drosophila melanogaster;Male;Genetic Complementation Test;Light;Mammals;Animals;Darkness;Shaker Superfamily of Potassium Channels;Phenotype;X Chromosome;Molecular Sequence Data;Drosophila Proteins;Homeostasis;Sleep;Motor Activity;Behavior, Animal;Crosses, Genetic;Longevity;research support, u.s. gov't, p.h.s.;research support, u.s. gov't, non-p.h.s.;Sleep Deprivation;Amino Acid Sequence;Point Mutation;Time Factors;Female;Potassium Channels;21 Neurophysiology;Genes, Recessive;Humans;Conserved Sequence}, Month = {4}, Nlm_Id = {0410462}, Number = {7037}, Organization = {Department of Psychiatry, 6001 Research Park Blvd, University of Wisconsin Madison, Madison, Wisconsin 53719, USA.}, Pages = {1087-92}, Pii = {nature03486}, Pubmed = {15858564}, Title = {Reduced sleep in Drosophila Shaker mutants}, Uuid = {F12C3AC1-E95D-448B-AC61-B4F635DE4F1E}, Volume = {434}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03486}} @article{Clancy:1999, Abstract = {Theories of information processing and plasticity in mammalian cortex often rely on knowledge of intracortical networks studied in rodent cortex. Accordingly, the contribution of all cells involved in this circuitry is potentially significant, including connections from a subset of neurons that persist from the developmental subplate, called subgriseal neurons in the present study. Ascending corticocortical connections from subgriseal neurons were identified by using in vivo transport of fluorescent retrograde tracers from discrete applications confined to cortical layer I (approximately 1 mm2) or from injections placed into superficial cortical layers. Applications restricted to cortical layer I can be identified by a subsequent retrograde labeling pattern that includes neurons in layers II/III and V but not those in layer IV. In contrast, when retrograde tracer is deposited in layers II/III, layer IV cells are also labeled. By using this identification technique in juvenile and adult rats, widespread interareal projections to superficial layers, including unequivocal connections to cortical layer I, were found to originate from a tangential band of neurons directly below the conventionally identified gray matter (i.e., subgriseal) and from a smaller number of cells in the white matter (WM) proper. Subgriseal and WM neurons were labeled below application and injection sites in somatosensory, auditory, visual, motor, frontal, and adjacent areas at distances of more than 4 mm. However, the subgriseal-to-superficial pathway was not sensitive to nonfluorescent retrograde tracers including horseradish peroxidase. Because neurons in the deeper cortical layers can be strongly influenced through input to their apical dendritic extensions in cortical layer I, the widespread connections described in the present study indicate that the ascending subgriseal projections should be considered in models of mature cortical function.}, Author = {Clancy, B. and Cauller, L. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Aging;Visual Cortex;Cerebral Cortex;Research Support, Non-U.S. Gov't;Rats, Sprague-Dawley;24 Pubmed search results 2008;Axonal Transport;Rats;Neuronal Plasticity;Motor Cortex;In Vitro;Horseradish Peroxidase;Male;Animals;Neurons;Frontal Lobe}, Medline = {99228083}, Month = {5}, Nlm_Id = {0406041}, Number = {2}, Organization = {Department of Psychology, Cornell University, Ithaca, New York 14853, USA. bec8\@cornell.edu}, Pages = {275-86}, Pii = {10.1002/(SICI)1096-9861(19990503)407:2<275::AID-CNE8>3.0.CO;2-0}, Pubmed = {10213095}, Title = {Widespread projections from subgriseal neurons (layer VII) to layer I in adult rat cortex}, Uuid = {47A8028D-5949-4A3D-A00C-A5B37BCF850A}, Volume = {407}, Year = {1999}} @article{Clarke:1990, Abstract = {The kitten's auditory cortex (including the first and second auditory fields AI and AII) is known to send transient axons to either ipsi- or contralateral visual areas 17 and 18. By the end of the first postnatal month the transitory axons, but not their neurons of origin, are eliminated. Here we investigated where these neurons project after the elimination of the transitory axon. Eighteen kittens received early (postnatal day (pd) 2 - 5) injections of long lasting retrograde fluorescent traces in visual areas 17 and 18 and late (pd 35 - 64) injections of other retrograde fluorescent tracers in either hemisphere, mostly in areas known to receive projections from AI and AII in the adult cat. The middle ectosylvian gyrus was analysed for double-labelled neurons in the region corresponding approximately to AI and AII. Late injections in the contralateral (to the analysed AI, AII) hemisphere including all of the known auditory areas, as well as some visual and 'association' areas, did not relabel neurons which had had transient projections to either ipsi- or contralateral visual areas 17 - 18. Thus, AI and AII neurons after eliminating their transient juvenile projections to visual areas 17 and 18 do not project to the other hemisphere. In contrast, relabelling was obtained with late injections in several locations in the ipsilateral hemisphere; it was expressed as per cent of the population labelled by the early injections. Few neurons (0 - 2.5\%) were relabelled by large injections in the caudal part of the posterior ectosylvian gyrus and the adjacent posterior suprasylvian sulcus (areas DP, P, VP). Multiple injections in the middle ectosylvian gyrus relabelled a considerably larger percentage of neurons (13\%). Single small injections in the middle ectosylvian gyrus (areas AI, AII), the caudal part of the anterior ectosylvian gyrus and the rostral part of the posterior ectosylvian gyrus relabelled 3.1 - 7.0\%of neurons. These neurons were generally near (<2.0 mm) the outer border of the late injection sites. Neurons with transient projections to ipsi- or contralateral visual areas 17 and 18 were relabelled in similar proportions by late injections at any given location. Thus, AI or AII neurons which send a transitory axon to ipsi- or contralateral visual areas 17 and 18 are most likely to form short permanent cortical connections. In that respect, they are similar to medial area 17 neurons that form transitory callosal axons and short permanent axons to ipsilateral visual areas 17 and 18.}, Author = {Clarke, and Innocenti,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:28 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Not relevant;11 Glia}, Nlm_Id = {8918110}, Number = {3}, Organization = {Institute of Anatomy, University of Lausanne, rue du Bugnon 9, 1005 Lausanne, Switzerland.}, Pages = {227-242}, Pii = {ejn_02030227}, Pubmed = {12106050}, Title = {Auditory Neurons with Transitory Axons to Visual Areas Form Short Permanent Projections}, Uuid = {E2BE8D9E-9EFB-44ED-BB9D-76573DC9CDEE}, Volume = {2}, Year = {1990}} @article{Clarke:1986, Abstract = {In the adult cat injections of retrograde fluorescent tracers near the border between areas 17 and 18 and extending to the underlying white matter label neurons in restricted parts of nine other ipsilateral visual areas. A very similar, restricted distribution of retrograde labeling is found in newborn kittens when injections near the 17/18 border are confined to the cortical gray matter. When, however, the neonatal 17/18 border injection reaches the underlying white matter, more visual areas and numerous nonvisual areas become labeled, each of them over nearly its whole tangential extent. Labeled nonvisual areas include the primary and secondary auditory areas, the auditory areas of the posterior ectosylvian gyrus, areas 7 and 5, the cingulate gyrus, and the primary and secondary somatosensory areas. The widespread labeling in kittens was not due to larger or differently placed injections, since the distribution and extent of retrograde labeling in the ipsilateral lateral geniculate nucleus were similar at all ages. The transitory projections from the auditory and somatosensory areas are not reciprocated by a projection from areas 17 or 18. In kittens injected around the end of the first postnatal month the distribution of labeled association neurons is similar to that found in the adult; i.e., many of the juvenile projections have been eliminated. Only a few of the transitory axons to areas 17 and 18 enter the gray matter; the others remain confined to the white matter. Some of these axons were anterogradely labeled with rhodamine-B-iso-thiocyanate from the auditory cortex; they show bulbous endings, some of which are probably growth cones. Retrograde double-labeling experiments showed that, in the newborn, some neurons on the lateral sulcus have at least two long collaterals, one running rostrally, the other caudally; such branching is not observed in adults. In conclusion, areas 17/18 receive at birth from a large, continuous territory including areas, or parts of areas, which will later eliminate these projections. Most of the transitory projections do not appear to enter the cortex to any great extent. The major reshaping of association projections occurs before the end of the first postnatal month. The development of association projections resembles that of callosal projections.}, Author = {Clarke, S. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Visual Cortex;Cats;Not relevant;Fluorescent Dyes;11 Glia;Animals, Newborn;Support, Non-U.S. Gov't;Animals}, Medline = {87009169}, Month = {9}, Nlm_Id = {0406041}, Number = {1}, Pages = {1-22}, Pubmed = {3760253}, Title = {Organization of immature intrahemispheric connections}, Uuid = {D923097F-0C00-42F2-89B9-FDF0501FD1E2}, Volume = {251}, Year = {1986}} @article{Clarke:1989, Abstract = {The sexual dimorphism of the human corpus callosum (CC) is currently controversial, possibly because of difficulties in morphometric analysis. We have reinvestigated the issue by using morphometric techniques specially designed to yield objective measurements of CC size and shape. The development of the CC was studied with similar techniques in order to investigate whether its final shape and size might be influenced by axonal elimination, as could be expected from previous animal studies. We have measured the CCs of 32 men and 26 women; 27 male and 19 female CCs were from brain tissue, the others were from magnetic resonance imaging graphs. Women tended to have 1) a smaller cross-sectional callosal area (CCA); 2) a larger fraction of CCA in the posterior fifth of the CC; 3) more slender CCs; and 4) more bulbous splenia. These differences could not be detected by simple inspection but were demonstrated by measurement and statistical analysis. However, CCA was correlated with the other sexually dimorphic parameters, and the sex-related differences in the latter became nonsignificant when variations in CCA were factored out or when male and female populations with similar CCA were compared. In addition, we analyzed CCs of 16 male and 16 female fetuses and of 13 male and 15 female infants and children. This sample ranged in age between 20 weeks of gestation and 14 years but covered in detail the period up to 14 months after birth. CCA increased throughout the latter period but decreased slightly between about 33 weeks of gestation and the beginning of the second postnatal mouth. This decrease coincided with thinning of the CC and a marked increase in bulbosity of the splenium. No sexual dimorphism could be demonstrated until the beginning of the postnatal period. In the age group between birth (at term) and the 14th month, CCA was, as in the adult, larger in males. Unlike in the adults, the CC was longer in males and the bulbosity index was the same in the two sexes. Axonal elimination may play a role in the perinatal pause in CCA growth and in the concomitant changes in callosal shape.}, Author = {Clarke, S. and Kraftsik, R. and Van der Loos, H. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Fetus;Human;Magnetic Resonance Imaging;Child, Preschool;Aging;Middle Aged;Embryo and Fetal Development;Female;Infant;Not relevant;11 Glia;Male;Aged;Support, Non-U.S. Gov't;Sex Characteristics;Adult;Infant, Newborn;Gestational Age;Corpus Callosum;Adolescent}, Medline = {89175582}, Month = {2}, Nlm_Id = {0406041}, Number = {2}, Organization = {Institute of Anatomy, University of Lausanne, Switzerland.}, Pages = {213-30}, Pubmed = {2925893}, Title = {Forms and measures of adult and developing human corpus callosum: is there sexual dimorphism?}, Uuid = {A1D29E42-C087-4494-A4CB-23D8A51D1ACB}, Volume = {280}, Year = {1989}} @article{Clauset:2008, Abstract = {Networks have in recent years emerged as an invaluable tool for describing and quantifying complex systems in many branches of science. Recent studies suggest that networks often exhibit hierarchical organization, in which vertices divide into groups that further subdivide into groups of groups, and so forth over multiple scales. In many cases the groups are found to correspond to known functional units, such as ecological niches in food webs, modules in biochemical networks (protein interaction networks, metabolic networks or genetic regulatory networks) or communities in social networks. Here we present a general technique for inferring hierarchical structure from network data and show that the existence of hierarchy can simultaneously explain and quantitatively reproduce many commonly observed topological properties of networks, such as right-skewed degree distributions, high clustering coefficients and short path lengths. We further show that knowledge of hierarchical structure can be used to predict missing connections in partly known networks with high accuracy, and for more general network structures than competing techniques. Taken together, our results suggest that hierarchy is a central organizing principle of complex networks, capable of offering insight into many network phenomena.}, Author = {Clauset, Aaron and Moore, Cristopher and Newman, M. E. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Models, Biological;Probability;Protein Binding;Food Chain;Biosynthetic Pathways;Algorithms;Metabolic Networks and Pathways;Sensitivity and Specificity;Gene Regulatory Networks;Social Behavior;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0410462}, Number = {7191}, Organization = {Department of Computer Science, University of New Mexico, Albuquerque, New Mexico 87131, USA. aaronc\@santafe.edu}, Pages = {98-101}, Pii = {nature06830}, Pubmed = {18451861}, Title = {Hierarchical structure and the prediction of missing links in networks}, Uuid = {6E3FF1F2-09D0-45C9-9AE4-2612A1526690}, Volume = {453}, Year = {2008}, url = {papers/Clauset_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06830}} @article{Clay:1999, Abstract = {The purpose of this review is to illustrate some of the technical and biological hurdles that need to be addressed when developing new gene therapy based clinical trials. Gene transfer approaches can be used to "mark" cells to monitor their persistence in vivo in patients, to protect cells from toxic chemotherapeutic agents, correct a genetic defect within the target cell, or to confer a novel function on the target cell. Selection of the most suitable vector for gene transfer depends upon a number of factors such as the target cell itself and whether gene expression needs to be sustained or transient. The TCR gene transfer approach described here represents one innovative strategy being pursued as a potential therapy for metastatic melanoma. Tumor reactive T cells can be isolated from the tumor infiltrating lymphocytes (TIL) of melanoma patients. A retroviral vector has been constructed containing the T cell receptor (TCR) alpha and beta chain genes from a MART-1-specific T cell clone (TIL 5). Jurkat cells transduced with this virus specifically release cytokine in response to MART-1 peptide pulsed T2 cells, showing that the virus can mediate expression of a functional TCR. HLA-A2 transgenic mice are being used to examine whether transduced bone marrow progenitor cells will differentiate in vivo into mature CD8+ T cells expressing the MART-1-specific TCR. Expression of the human TCR alpha and beta chain genes has been detected by RT-PCR in the peripheral blood of HLA-A2 transgenic mice reconstituted with transduced mouse bone marrow. Expression of the TIL 5 TCR genes in the peripheral blood of these mice was maintained for greater than 40 weeks after bone marrow reconstitution. TIL 5 TCR gene expression was also maintained following transfer of bone marrow from mice previously reconstituted with transduced bone marrow to secondary mouse recipients, suggesting that a pluripotent progenitor or lymphocyte progenitor cell has been transduced.}, Author = {Clay, T. M. and Custer, M. C. and Spiess, P. J. and Nishimura, M. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {1219-4956}, Journal = {Pathol Oncol Res}, Keywords = {Cell Differentiation;Jurkat Cells;Genetic Vectors;Receptors, Antigen, T-Cell, alpha-beta;Melanoma;T-Lymphocytes, Cytotoxic;Gene Therapy;Epitopes;Animals;Lymphocytes, Tumor-Infiltrating;Gene Expression;Transfection;Mice, Inbred C57BL;Hematopoietic Stem Cells;Neoplasm Metastasis;11 Glia;Hematopoietic Stem Cell Transplantation;Neoplasm Proteins;HLA-A2 Antigen;Lymphokines;Retroviridae;Graft Survival;COS Cells;review;Radiation Chimera;Mice, Inbred C3H;Mice;review, tutorial;Humans;Mice, Transgenic;Reverse Transcriptase Polymerase Chain Reaction}, Medline = {99180734}, Nlm_Id = {9706087}, Number = {1}, Organization = {National Cancer Institute, National Institutes of Health, Surgery Branch, Bethesda, MD 20892, USA. Tim\_Clay\@nih.gov.usa}, Pages = {3-15}, Pubmed = {10079371}, Title = {Potential use of T cell receptor genes to modify hematopoietic stem cells for the gene therapy of cancer}, Uuid = {D8E5848C-F90F-40F7-AFE7-7DC3E697EB67}, Volume = {5}, Year = {1999}} @article{Cobos:2005, Abstract = {Dlx homeodomain transcription factors are essential during embryonic development for the production of forebrain GABAergic interneurons. Here we show that Dlx1 is also required for regulating the functional longevity of cortical and hippocampal interneurons in the adult brain. We demonstrate preferential Dlx1 expression in a subset of cortical and hippocampal interneurons which, in postnatal Dlx1 mutants, show a time-dependent reduction in number. This reduction preferentially affects calretinin(+) (bipolar cells) and somatostatin(+) subtypes (for example, bitufted cells), whereas parvalbumin(+) subpopulations (basket cells and chandelier cells) seem to be unaffected. Cell transplantation analysis demonstrates that interneuron loss reflects cell-autonomous functions of Dlx1. The decrease in the number of interneurons was associated with a reduction of GABA-mediated inhibitory postsynaptic current in neocortex and hippocampus in vitro and cortical dysrhythmia in vivo. Dlx1 mutant mice show generalized electrographic seizures and histological evidence of seizure-induced reorganization, linking the Dlx1 mutation to delayed-onset epilepsy associated with interneuron loss.}, Author = {Cobos, Inma and Calcagnotto, Maria Elisa and Vilaythong, Alex J. and Thwin, Myo T. and Noebels, Jeffrey L. and Baraban, Scott C. and Rubenstein, John L. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {gamma-Aminobutyric Acid;Animals;Synapses;Aging;Brain;Apoptosis;Homeodomain Proteins;Epilepsy;Cell Count;21 Epilepsy;Gene Deletion;Behavior, Animal;Research Support, U.S. Gov't, P.H.S.;Mice, Knockout;Neurons;21 Neurophysiology;Cerebral Cortex;Mice;Interneurons;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Neural Inhibition;12 Interneuron development;Research Support, Non-U.S. Gov't}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California San Francisco, San Francisco, California 94158, USA. icobos\@itsa.ucsf.edu}, Pages = {1059-68}, Pii = {nn1499}, Pubmed = {16007083}, Title = {Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy}, Uuid = {890F4BC0-8C79-47AD-BCC2-76565AB7090D}, Volume = {8}, Year = {2005}, url = {papers/Cobos_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1499}} @article{Cogle:2004, Abstract = {Background End-organ repair by adult haemopoietic stem cells is under great scrutiny with investigators challenging the notion of these cells'plasticity. Some investigations of animals and short-term human bone marrow transplants suggest that bone marrow can repair brain. We looked for evidence of clinically relevant marrow-derived restorative neurogenesis: long-term, multilineage, neural engraftment that is not the result of cell-fusion events. Methods We examined autopsy brain specimens from three sex-mismatched female bone-marrow-transplantation patients, a female control, and a male control. We did immunohistochemistry, fluorescence in-situ hybridisation, and tissue analysis to look for multilineage, donor-derived neurogenesis. Findings Hippocampal cells containing a Y chromosome were present up to 6 years post-transplant in all three patients. Transgender neurons accounted for 1\%of all neurons; there was no evidence of fusion events since only one X chromosome was present. Moreover, transgender astrocytes and microglia made up 1-2\%of all glial cells. Interpretation Postnatal human neuropoiesis happens, and human haemopoietic cells can transdifferentiate into neurons, astrocytes, and microglia in a long-term setting without fusing. Transplantable human haemopoietic cells could serve as a therapeutic source for long-term regenerative neuropoiesis. 1474-547x Journal Article}, Author = {Cogle, C. R. and Yachnis, A. T. and Laywell, E. D. and Zander, D. S. and Wingard, P. J. and Steindler, P. D. and Scott, E. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {Lancet}, Keywords = {EE, L pdf}, Number = {9419}, Organization = {Program in Stem Cell Biology and Regenerative Medicine, University of Florida Shands Cancer Center, Gainesville, FL, USA.}, Pages = {1432-7}, Title = {Bone marrow transdifferentiation in brain after transplantation: a retrospective study}, Uuid = {794DD876-D3AF-11D9-A0E9-000D9346EC2A}, Volume = {363}, Year = {2004}, url = {papers/Cogle_Lancet2004.pdf}} @article{Cogswell:1998, Abstract = {A recently discovered, spontaneous, autosomal recessive mutation in rats, flathead (fh), results in greatly reduced brain growth beginning in late fetal development. In this study we have mapped the fh mutation by determining the pattern of segregation of polymorphic microsatellite markers with respect to fh in 51 affected F2 offspring from a single interstrain intercross. Two markers on chromosome 12, D12Rat80 and D12Mgh6, cosegregated with the fh mutation in all 51 affected animals. The distribution of six additional markers in 40 informative meioses further localizes fh approximately 2 cM teleomeric to nos1. There are no known mutations in homologous regions of either mouse or human genomes that result in deficits in late neurodevelopment similar to that observed in fh/fh animals. The unique phenotype of fh/fh animals and the location of fh suggests the presence of a novel gene essential to normal brain development on the distal end of rat chromosome 12.}, Author = {Cogswell, C. A. and Sarkisian, M. R. and Leung, V. and Patel, R. and D'Mello, S. R. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Genetic Markers;Rats, Mutant Strains;Animals;Genes, Recessive;Humans;Aging;Rats;Phenotype;Brain;Female;Lod Score;Rats, Wistar;Embryonic and Fetal Development;Crosses, Genetic;Male;Homozygote;Mice;Chromosome Mapping;Genes, Essential}, Medline = {98378253}, Month = {7}, Nlm_Id = {7600130}, Number = {1}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269-4156, USA.}, Pages = {5-8}, Pii = {S0304394098004789}, Pubmed = {9714451}, Title = {A gene essential to brain growth and development maps to the distal arm of rat chromosome 12}, Uuid = {B85E5D54-69B0-11DA-A4B6-000D9346EC2A}, Volume = {251}, Year = {1998}, url = {papers/Cogswell_NeurosciLett1998.pdf}} @article{Coil:2004, Abstract = {The envelope protein from vesicular stomatitis virus (VSV) has become an important tool for gene transfer and gene therapy. It is widely used mainly because of its ability to mediate virus entry into all cell types tested to date. Consistent with the broad tropism of the virus, the receptor for VSV is thought to be a ubiquitous membrane lipid, phosphatidylserine (PS). However, the evidence for this hypothesis is indirect and incomplete. Here, we have examined the potential interaction of VSV and PS at the plasma membrane in more detail. Measurements of cell surface levels of PS show a wide range across cell types from different organisms. We demonstrate that there is no correlation between the cell surface PS levels and VSV infection or binding. We also demonstrate that an excess of annexin V, which binds specifically and tightly to PS, does not inhibit infection or binding by VSV. While the addition of PS to cells does allow increased virus entry, we show that this effect is not specific to the VSV envelope. We conclude that PS is not the cell surface receptor for VSV, although it may be involved in a postbinding step of virus entry.}, Author = {Coil, David A. and Miller, A. Dusty}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {15 PS VSVG receptor;Cell Membrane;Phosphatidylserines;Receptors, Cell Surface;Cricetinae;Cell Line;Annexin A5;Research Support, U.S. Gov't, P.H.S.;Receptors, Virus;Vesicular stomatitis-Indiana virus;Dogs;15 Retrovirus mechanism;Animals;Humans;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0113724}, Number = {20}, Organization = {Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Room C2-105, P.O. Box 19024, Seattle, WA 98109-1024, USA.}, Pages = {10920-6}, Pii = {78/20/10920}, Pubmed = {15452212}, Title = {Phosphatidylserine is not the cell surface receptor for vesicular stomatitis virus}, Uuid = {D0F5469D-DDC6-42E6-8510-0D78677E7ABE}, Volume = {78}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.78.20.10920-10926.2004}} @article{Coil:2005, Abstract = {Enveloped virus vectors are used in a wide variety of applications. We have discovered that treatment of cultured cells with phosphatidylserine (PS) liposomes can increase virus vector infection by up to 20-fold. This effect does not abrogate virus receptor requirements, is specific to PS compared to other phospholipids, and is limited to enveloped viruses. Furthermore, the enhancement of infection does not occur through increases in virus receptor levels or virus binding, indicating that virus fusion is enhanced. The liposomes are easily generated, store well, and allow enhanced infection with a variety of virus vectors and cell types.}, Author = {Coil, David A. and Miller, A. Dusty}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {15 PS VSVG receptor;Phosphatidylserines;Virus Replication;Cell Line;Retroviridae;Research Support, U.S. Gov't, P.H.S.;Research Support, N.I.H., Extramural;15 Retrovirus mechanism;Humans;Animals;24 Pubmed search results 2008;Genetic Vectors}, Month = {9}, Nlm_Id = {0113724}, Number = {17}, Organization = {Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.}, Pages = {11496-500}, Pii = {79/17/11496}, Pubmed = {16103200}, Title = {Enhancement of enveloped virus entry by phosphatidylserine}, Uuid = {EFC78F89-375C-4D53-B511-2B695B95C59D}, Volume = {79}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.79.17.11496-11500.2005}} @article{Coil:2005a, Abstract = {BACKGROUND: A major determinant of retrovirus host range is the presence or absence of appropriate cell-surface receptors required for virus entry. Often orthologs of functional receptors are present in a wide range of species, but amino acid differences can render these receptors non-functional. In some cases amino acid differences result in additional N-linked glycosylation that blocks virus infection. The latter block to retrovirus infection can be overcome by treatment of cells with compounds such as tunicamycin, which prevent the addition of N-linked oligosaccharides. RESULTS: We have discovered that treatment of cells with liposomes composed of phosphatidylserine (PS) can also overcome the block to infection mediated by N-linked glycosylation. Importantly, this effect occurs without apparent change in the glycosylation state of the receptors for these viruses. This effect occurs with delayed kinetics compared to previous results showing enhancement of virus infection by PS treatment of cells expressing functional virus receptors. CONCLUSION: We have demonstrated that PS treatment can relieve the block to retrovirus infection of cells expressing retroviral receptors that have been rendered non-functional by glycosylation. These findings have important implications for the current model describing inhibition of virus entry by receptor glycosylation.}, Author = {Coil, David A. and Miller, A. Dusty}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1742-4690}, Journal = {Retrovirology}, Keywords = {15 PS VSVG receptor;15 Retrovirus mechanism;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {101216893}, Organization = {Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, USA. coild\@u.washington.edu}, Pages = {49}, Pii = {1742-4690-2-49}, Pubmed = {16091143}, Title = {Phosphatidylserine treatment relieves the block to retrovirus infection of cells expressing glycosylated virus receptors}, Uuid = {19DFEABE-41DC-47BB-84FB-A7D9D942B230}, Volume = {2}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1742-4690-2-49}} @article{Colacitti:1998, Abstract = {We are currently investigating various treatments which could determine, in the rat brain, structural abnormalities mimicking those reported in human brain dysgeneses. We can induce the formation of neuronal heterotopia in the progeny of rats by means of a double injection of the cytotoxic agent methylazoxymethanol acetate (MAM) on embryonic day 15. We have now investigated the anatomical connections of these heterotopia by means of anterograde and retrograde tract tracing techniques. The induced heterotopia along the border of the lateral ventricles shared common anatomical features with the periventricular nodules in human periventricular or subcortical nodular heterotopia (PNH). The tract tracing data demonstrated the existence of reciprocal connections between the neuronal heterotopia and the ipsilateral and contralateral cortical areas, and the presence of abnormal cortico-hippocampal and cortico-cortical connections. On the basis of the connectivity patterns, it may be speculated that some cells in the heterotopia could be neurons originally committed to the cortex, that were interrupted in their migration by the MAM treatment. Given the common morphological features seen in human PNH and MAM-induced brain heterotopia, the anatomical and developmental analysis of MAM-treated rats may shed light on the mechanisms by which human brain dysgeneses develop in human patients.}, Author = {Colacitti, C. and Sancini, G. and Franceschetti, S. and Cattabeni, F. and Avanzini, G. and Spreafico, R. and Di Luca, M. and Battaglia, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:42 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {10 Development;Pregnancy;Animals;Humans;Rats;Functional Laterality;Neocortex;Female;Brain;Rats, Sprague-Dawley;21 Epilepsy;Disease Models, Animal;Teratogens;Brain Diseases;Axonal Transport;10 genetics malformation;Neurons;21 Neurophysiology;Methylazoxymethanol Acetate;Laterality;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Choristoma;Gestational Age;Research Support, Non-U.S. Gov't}, Medline = {98432475}, Month = {9}, Nlm_Id = {8703089}, Number = {1-2}, Organization = {Department of Neurophysiology, Neurological Institute C. Besta, Milano, Italy.}, Pages = {49-62}, Pii = {S0920-1211(98)00039-4}, Pubmed = {9761308}, Title = {Altered connections between neocortical and heterotopic areas in methylazoxymethanol-treated rat}, Uuid = {B2F06771-7461-4660-B6D5-E47DED8AF90A}, Volume = {32}, Year = {1998}, url = {papers/Colacitti_EpilepsyRes1998.pdf}} @article{Colavincenzo:2000, Abstract = {We have examined the clearance of myelin debris from the visual pathways of the goldfish during Wallerian degeneration. Both the rate and pattern of myelin disappearance from the optic nerve and tract were determined using immunohistochemistry on frozen sections, as well as plastic sections and electron microscopy. Animals with and without regenerating optic axons were examined in order to determine whether the axons play a role in myelin clearance. We found that myelin is cleared at different rates along the visual paths. Thus, virtually all myelin debris is gone in the optic tract and distal optic nerve stump by 4 weeks after surgery, while in the cranial nerve segment, myelin clearance is still incomplete at 6 weeks postoperative. These temporal and spatial patterns of myelin clearance are the same in animals with and without regenerating axons, thus indicating that growing axons do not influence this process. Finally, ultrastructural observations revealed that both astrocytes and microglia participate in phagocytosing myelin debris in the optic nerve, while in the tract, the vast majority of debris is removed by microglia alone. These data are discussed with regard to possible mechanisms controlling the differential expression of myelin clearance.}, Author = {Colavincenzo, J. and Levine, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Wallerian Degeneration;Goldfish;Cytokines;Nerve Regeneration;Myelin Sheath;Astrocytes;Microscopy, Electron;Not relevant;11 Glia;Optic Nerve;Animals;Visual Pathways;Phagocytosis;Support, Non-U.S. Gov't}, Medline = {20121686}, Month = {1}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Biology, McGill University, Montr{\'e}al, Qu{\'e}bec, Canada.}, Pages = {47-62}, Pii = {10.1002/(SICI)1097-4547(20000101)59:1<47::AID-JNR7>3.0.CO;2-P}, Pubmed = {10658185}, Title = {Myelin debris clearance during Wallerian degeneration in the goldfish visual system}, Uuid = {657F374F-2CEE-4454-9C85-C99DF6D0095A}, Volume = {59}, Year = {2000}} @article{Colgin:2006, Author = {Colgin, Laura L. and Moser, Edvard I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {comment;24 Pubmed search results 2008;news}, Month = {3}, Nlm_Id = {0410462}, Number = {7084}, Pages = {615-7}, Pii = {440615a}, Pubmed = {16572155}, Title = {Neuroscience: rewinding the memory record}, Uuid = {8503960B-F62C-4BF8-9634-7A6AC91413A6}, Volume = {440}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/440615a}} @article{Collard:2004, Author = {Collard, John G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {02 Adult neurogenesis migration;10 Development;Cell Cycle Proteins;Tumor Suppressor Proteins;Human;rhoA GTP-Binding Protein;Cell Division;Neoplasms;Animals;Cell Movement;news}, Month = {4}, Nlm_Id = {0410462}, Number = {6984}, Pages = {705-8}, Pii = {428705a}, Pubmed = {15085115}, Title = {Cancer: Kip moving}, Uuid = {9FAC1314-FF4E-4C6E-AAE2-BCBC3267F136}, Volume = {428}, Year = {2004}, url = {papers/Collard_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/428705a}} @article{Colom:2006, Abstract = {A series of experiments was carried out testing the hypothesis that the septal region decreases the hippocampal susceptibility to hyperexcitability states through theta rhythm generation. Medial septal neurons were simultaneously recorded with hippocampal field potentials to investigate the septo-hippocampal function in the pilocarpine model of chronic epilepsy. The theta rhythm from chronically epileptic rats had lower amplitude (20\%less) and higher frequency than controls (from 3.38 to 4.25 Hz), suggesting that both generator and pacemaker structures are affected during the epileptic process. At the cellular level, the group of rhythmically bursting firing medial septal neurons, in the epileptic animals, significantly and chronically increased their firing rates in relation to controls (from 13.86 to 29.14 spikes/s). Peristimulus histograms performed around hippocampal sharp waves showed that all high-frequency firing neurons, including rhythmically bursting neurons and most slow firing neurons, decreased firing rates immediately after hippocampal epileptic discharges. Thus inhibitory hippocampo-septal influences prevail during hippocampal epileptic discharges. The occurrence of epileptic discharges was reduced 86-97\%of the number observed during spontaneous theta and theta induced by sensory (tail pinch) or chemical stimulation (carbachol), suggesting that the presence of the theta state regardless of how it was produced was responsible for the reduction in epileptic discharge frequency. The understanding of the theta rhythm "anti-epileptic" effect at the cellular and molecular levels may result in novel therapeutic approaches dedicated to protect the brain against abnormal excitability states.}, Author = {Colom, Luis V. and Garc{\'\i}a-Hern{\'a}ndez, Antonio and Casta\~{n}eda, Maria T. and Perez-Cordova, Miriam G. and Garrido-Sanabria, Emilio R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {research support, n.i.h., extramural ;Pilocarpine;Animals;Feasibility Studies;Rats;Theta Rhythm;Neural Pathways;Septum of Brain;Rats, Sprague-Dawley;Hippocampus;Biological Clocks;Chronic Disease;Action Potentials;Epilepsy, Temporal Lobe;21 Neurophysiology;Drug Delivery Systems;24 Pubmed search results 2008;Anticonvulsants}, Month = {6}, Nlm_Id = {0375404}, Number = {6}, Organization = {Department of Biological Sciences and Center for Biomedical Studies, The University of Texas at Brownsville/Texas Southmost College, USA. luis.colom\@utb.edu}, Pages = {3645-53}, Pii = {00040.2006}, Pubmed = {16554504}, Title = {Septo-hippocampal networks in chronically epileptic rats: potential antiepileptic effects of theta rhythm generation}, Uuid = {189A606F-4943-4F1B-9EA0-5820F9B20F0E}, Volume = {95}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00040.2006}} @article{Colombo:1997, Abstract = {Long astroglial processes traversing several cortical laminae appear to be characteristic of primate brains. Whether interlaminar processes develop as a modification of radial glia or are truly postnatal elements stemming from stellate astroglia, could be assessed by analyzing their early developmental stages. A survey of glial fibrillar acidic protein immunoreactive (GFAP-IR) astroglial interlaminar processes in the cerebral cortex of Ceboidea monkeys at various postnatal developmental ages, and in human cortical samples of a ten day and a seven year old child disclosed that such processes develop postnatally. At one month of age GFAP-IR interlaminar processes in monkeys were scarce and short in most frontal, parietal or occipital (striate) cortical areas, except for sulcal (principal and orbital sulci) and temporal cortical areas. Some processes were weakly positive for vimentin, and these were most abundant in ventral temporal cortical areas. At two months of age processes were present in all these areas, albeit in restricted patches and significantly shorter than in adults. The expression of this pattern was increased at seven months of age. At three years of age almost every area showed abundant processes and with lengths comparable to the adult Ceboidea individuals. In humans, at 10 days of age long interlaminar processes were readily apparent in a frontal cortex sample, becoming most apparent at the age of seven years although not reaching yet the adult characteristics as described previously. CONCLUSIONS: (1) GFAP-IR interlaminar processes develop postnatally, thus typifying a subtype of the classical stellate forms; (2) they bear no obvious direct relationship with radial glia; (3) their development is not contemporary among the various cortical regions. These long cellular processes represent an addition to those already described for other astroglial cell types in the adult mammalian brain (Golgi-Bergmann glia, tanicytes, Muller cells).}, Author = {Colombo, J. A. and Lipina, S. and Yanez, A. and Puissant, V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Int J Dev Neurosci}, Keywords = {Species Specificity;Cerebral Cortex/*growth &development;Human;Immunohistochemistry;Glial Fibrillary Acidic Protein/analysis;Astrocytes/*physiology/ultrastructure;11 Glia;Animal;Cebus;Saimiri;Support, Non-U.S. Gov't;G;Child;Infant, Newborn}, Number = {7}, Organization = {Programa Unidad de Neurobiologia Aplicada (PRUNA) (CEMIC-CONICET), Buenos Aires, Argentina. colombo\@pruna.gov.ar}, Pages = {823-33.}, Title = {Postnatal development of interlaminar astroglial processes in the cerebral cortex of primates}, Uuid = {8CEFFDC9-AA39-435F-AA95-8B8F75A40614}, Volume = {15}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9580494}} @article{Colombo:2007, Abstract = {ARX loss-of-function mutations cause X-linked lissencephaly with ambiguous genitalia (XLAG), a severe neurological condition that results in profound brain malformations, including microcephaly, absence of corpus callosum, and impairment of the basal ganglia. Despite such dramatic defects, their nature and origin remain largely unknown. Here, we used Arx mutant mice as a model to characterize the cellular and molecular mechanisms underlying the basal ganglia alterations. In these animals, the early differentiation of this tissue appeared normal, whereas subsequent differentiation was impaired, leading to the periventricular accumulation of immature neurons in both the lateral ganglionic eminence and medial ganglionic eminence (MGE). Both tangential migration toward the cortex and striatum and radial migration to the globus pallidus and striatum were greatly reduced in the mutants, causing a periventricular accumulation of NPY+ or calretinin+ neurons in the MGE. Arx mutant neurons retained their differentiation potential in vitro but exhibited deficits in morphology and migration ability. These findings imply that cell-autonomous defects in migration underlie the neuronal localization defects. Furthermore, Arx mutants lacked a large fraction of cholinergic neurons and displayed a strong impairment of thalamocortical projections, in which major axon fiber tracts failed to traverse the basal ganglia. Altogether, these results highlight the critical functions of Arx in promoting neural migration and regulating basal ganglia differentiation in mice, consistent with the phenotype of XLAG patients.}, Author = {Colombo, Elena and Collombat, Patrick and Colasante, Gaia and Bianchi, Marta and Long, Jason and Mansouri, Ahmed and Rubenstein, John L. R. and Broccoli, Vania}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;Cell Differentiation;Animals;Basal Ganglia;Cells, Cultured;Genitalia;Mice, Mutant Strains;Transcription Factors;Pregnancy;Homeodomain Proteins;Cell Movement;Female;Substantia Nigra;Mice, Inbred C57BL;Organ Culture Techniques;research support, non-u.s. gov't;Male;Septal Nuclei;Animals, Newborn;Thalamus;X Chromosome;Cerebral Cortex;Globus Pallidus;research support, n.i.h., extramural;Mice;Interneurons;24 Pubmed search results 2008;12 Interneuron development}, Month = {4}, Nlm_Id = {8102140}, Number = {17}, Organization = {Stem Cell Research Department, San Raffaele Scientific Institute, 20132 Milan, Italy.}, Pages = {4786-98}, Pii = {27/17/4786}, Pubmed = {17460091}, Title = {Inactivation of Arx, the murine ortholog of the X-linked lissencephaly with ambiguous genitalia gene, leads to severe disorganization of the ventral telencephalon with impaired neuronal migration and differentiation}, Uuid = {18F33651-D0F0-40F7-8416-D4522CB63A37}, Volume = {27}, Year = {2007}, url = {papers/Colombo_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0417-07.2007}} @article{Colonnese:2006, Abstract = {During a short perinatal interval, N-methyl-D-aspartate receptor (NMDAR) function is essential to a process in which spontaneous retinal waves focus retinal axon arbors in the superficial layers of the rodent superior colliculus (sSC). Here we provide evidence that this NMDAR-dependent axonal refinement occurs through elimination of uncorrelated retinal synapses arising from disparate loci, rather than stabilization of topographically appropriate inputs. The density of synaptic release sites within fluorescently labeled retinal terminals was counted in double-labeling experiments using confocal microscopy and antibodies against synaptophysin or synapsin-1. Chronic NMDAR blockade from birth increased retinal axon synapse density at postnatal days (P) 6, 8, and 10, suggesting that NMDAR currents reduce synapse density during the refinement period. With assay at P14, after focal arborization has been established, the effect disappeared. Conversely, chronic NMDA treatment, known to induce functional synaptic depression in the sSC, decreased retinocollicular synapse density at P14, but not earlier, during the refinement period (P8). Thus during the development of retinocollicular topographic order, there is a period when NMDAR activity predominantly eliminates retinal axon synapses. We were able to extend this period by using retinal lesions to reduce synaptic density in a defined zone. Synapse density on intact retinocollicular axons sprouting into this zone was increased by NMDAR blockade, even when examined at P14. Thus, the period of NMDAR-dependent synaptic destabilization is terminated by a factor related to the density and refinement of retinal arbors.}, Author = {Colonnese, Matthew T. and Constantine-Paton, Martha}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Retina;research support, n.i.h., extramural ;Animals;Synapses;Rats;Neuronal Plasticity;Visual Pathways;Synaptophysin;Axons;Rats, Sprague-Dawley;comparative study ;Statistics, Nonparametric;Superior Colliculus;21 Neurophysiology;Synapsins;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Retinal Ganglion Cells}, Month = {2}, Nlm_Id = {0406041}, Number = {5}, Organization = {McGovern Institute for Brain Research, Department of Biology, Cambridge, Massachusetts 02139-4307, USA. mcolonne\@mit.edu}, Pages = {738-51}, Pubmed = {16374812}, Title = {Developmental period for N-methyl-D-aspartate (NMDA) receptor-dependent synapse elimination correlated with visuotopic map refinement}, Uuid = {316232C7-5465-4373-912A-519987B20126}, Volume = {494}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20841}} @article{Colonnese:2003, Abstract = {The activity of the N-methyl-D-aspartate receptor (NR) regulates the composition of excitatory synapses and mediates multiple forms of synaptic and structural plasticity. In the superficial superior colliculus (sSC) of the rat, NR activity is essential for the full refinement of retinotopy during development. We have examined the NR's role in synaptic development by chronically treating the sSC from birth with the competitive antagonist (+/-)-2-amino-5-phosphonopentanoic acid (AP5) released by the slow-release polymer Elvax. Whole-cell voltage-clamp recordings were used to characterize excitatory postsynaptic potentials (EPSCs) in slices from postnatal day (P)12-20 sSC. Chronic NR blockade reduced the ratio of AMPA/kainate receptor (AMPAR) to NR peak current amplitudes of both spontaneous (s)EPSCs and evoked EPSCs. Spontaneous NR current amplitude was increased following treatment, while spontaneous AMPAR currents were identical to those of controls, indicating that the ratio change was due to an increased NR current. Comparison of sEPSC frequency, AMPAR current rectification, and quantitative Western blots indicated that the characteristics of AMPARs at the synapse are normal following AP5 treatment. In the sSC, NR currents show a rapid decrease in decay time on P11 and previous studies in slices indicate this change results from a NR-mediated activation of the phosphatase calcineurin. Consistent with this in vitro finding, the down-regulation failed to occur in sSC chronically treated with AP5 in vivo. Together the present data show that NR function is necessary for subsequent NR current regulation in vivo, but it is not essential for the developmental expression of normal AMPAR currents.}, Author = {Colonnese, Matthew T. and Shi, Jian and Constantine-Paton, Martha}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Pregnancy;Animals;Synapses;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Rats;research support, u.s. gov't, p.h.s. ;Brain;Excitatory Amino Acid Agonists;Female;Rats, Sprague-Dawley;Receptors, AMPA;Calcium;Kainic Acid;N-Methylaspartate;21 Neurophysiology;Receptors, Kainic Acid;Adaptation, Physiological;Age Factors;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Biology, Department of Brain and Cognitive Science, and McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge 02139, USA.}, Pages = {57-68}, Pubmed = {12522159}, Title = {Chronic NMDA receptor blockade from birth delays the maturation of NMDA currents, but does not affect AMPA/kainate currents}, Uuid = {4D30F64E-38ED-4946-91BF-A5CA0A9E383C}, Volume = {89}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00049.2002}} @article{Colonnese:2001, Abstract = {We have investigated the role of the NMDA glutamate receptor (NMDAR) in the genesis and regulation of structural plasticity during synaptogenesis in the visual layers of the rat superior colliculus (sSC). In this neuropil, three projections compete for synaptic space during development. By fluorescently labeling the projections of both eyes and imaging them with confocal microscopy, we can quantify the sprouting of the ipsilateral retinal projection that follows removal of a portion of the contralateral retinal and/or corticocollicular projection. Using these techniques we have studied the effects of NMDAR blockade under different levels of competition. NMDARs were chronically blocked from birth [postnatal day 0 (P0)] by suspending the competitive antagonist 2-amino-5-phosphonopentanoic acid in the slow release plastic Elvax, a slab of which was implanted over the sSC. Such treatment alone does not impair the normal segregation of the retinal projections. However, if sprouting of the ipsilateral projection is initiated with a small contralateral retinal lesion at P6, this sprouting can be further increased by blocking NMDARs from birth. Sprouting of the ipsilateral retinal projection is also induced by retinal lesions made at P10/P11, but NMDAR blockade does not augment the sprouting induced by this later lesion. However, when combined with simultaneous ablation of the ipsilateral visual cortex, P10/P11 lesions show increased sprouting after NMDAR blockade. These data indicate that P0 NMDAR blockade does not eliminate synaptic competition in the sSC. Instead, early elimination of NMDAR function appears to facilitate sprouting that is gated in a stepwise manner by the other visual afferents.}, Author = {Colonnese, M. T. and Constantine-Paton, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Drug Implants;Retina;Animals;Fluorescent Dyes;Rats;Neuronal Plasticity;research support, u.s. gov't, p.h.s. ;Visual Pathways;Cell Count;Rats, Sprague-Dawley;2-Amino-5-phosphonovalerate;Axons;Animals, Newborn;Superior Colliculus;21 Neurophysiology;Scotoma;Occipital Lobe;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Cerebral Decortication;Retinal Ganglion Cells}, Month = {3}, Nlm_Id = {8102140}, Number = {5}, Organization = {Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06520, USA.}, Pages = {1557-68}, Pii = {21/5/1557}, Pubmed = {11222646}, Title = {Chronic NMDA receptor blockade from birth increases the sprouting capacity of ipsilateral retinocollicular axons without disrupting their early segregation}, Uuid = {0E21198C-91D2-441F-8D92-3435B8915193}, Volume = {21}, Year = {2001}} @article{Colonnese:2005, Abstract = {NMDA receptors (NMDARs) play an important role in the structural maintenance and functional strength of synapses. The causal relationship between these anatomical and functional roles is poorly defined. Using quantitative confocal microscopy, synaptic vesicle immunoreactivity, and differential label of retinal projections, we measured axon volume and synapse density along ipsilateral retinal axons (ipsi axons) sprouting into the superficial visual layers of the superior colliculus (sSC) deafferented by a contralateral retinal lesion (a scotoma) 8 d earlier. When retinal lesions were made at postnatal day 6 (P6), glutamatergic synaptic currents on neurons within the scotoma were significantly reduced. Both ipsi axon sprouting and synapse density were increased by chronic d-AP-5 antagonism of NMDARs. Conversely, ipsi axon sprouting and synapse density were reduced by chronic exposure to the agonist, NMDA, known to functionally depress glutamate transmission in this system. After P11 lesions, however, NMDAR blockade had no effect on sprouting or synapse density. Developmental changes in NMDAR current kinetics could not account for this difference in the structural effects of NMDAR function. Also, synaptic current frequencies within the scotoma were not affected after the P11 lesions. The corticocollicular projection matures during the P11 survival interval and, as indicated by previous work, it is a source of competition for synaptic space and probably of maintained activity in the older sSC. Thus, our results suggest that during early development, NMDAR currents predominantly destabilize nascent synapses. As the neuropil matures, however, competition for synaptic space suppresses axon sprouting and synapse formation regardless of NMDAR function.}, Author = {Colonnese, Matthew T. and Zhao, Jian-Ping P. and Constantine-Paton, Martha}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Retina;research support, n.i.h., extramural ;Animals;Synapses;Rats;Microscopy, Confocal;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Excitatory Amino Acid Agonists;Patch-Clamp Techniques;Rats, Sprague-Dawley;Visual Pathways;Receptors, AMPA;Axons;Depression, Chemical;Time Factors;Nerve Regeneration;Single-Blind Method;Receptors, GABA-A;N-Methylaspartate;21 Neurophysiology;Superior Colliculus;Scotoma;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Retinal Ganglion Cells}, Month = {2}, Nlm_Id = {8102140}, Number = {5}, Organization = {McGovern Institute for Brain Research, Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. mcolonne\@mit.edu}, Pages = {1291-303}, Pii = {25/5/1291}, Pubmed = {15689567}, Title = {NMDA receptor currents suppress synapse formation on sprouting axons in vivo}, Uuid = {38700E5F-801F-4A86-9560-36E9A212CFC6}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4063-04.2005}} @article{Colonnese:2008, Abstract = {Functional magnetic resonance imaging (fMRI) is a valuable method for probing postnatal circuit refinement and plasticity. However, its use during early development has been hindered by uncertainty as to the nature of neurovascular coupling in young individuals. Here we used somatosensory stimulation in rats to determine age-related parameters of the blood oxygenation level-dependent (BOLD) signal from its apparent inception on postnatal day 13 to adulthood. By comparing fMRI measurements with electrophysiological recordings, we determined that the regional BOLD response in these animals undergoes a systematic decline in latency and growth in amplitude over this period. We found no evidence of negative BOLD at any age. Maturation of hemodynamic responses correlated with age-dependent increases in susceptibility to inhibition of carbonic anhydrase. With knowledge of the infant BOLD response characteristics, we showed that interhemispheric and higher-order cortical stimulus responses are enhanced during the first several weeks after birth.}, Author = {Colonnese, Matthew T. and Phillips, Marnie A. and Constantine-Paton, Martha and Kaila, Kai and Jasanoff, Alan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {9809671}, Number = {1}, Organization = {McGovern Institute for Brain Research, 150 Albany St., NW14-2213, Cambridge, Massachusetts 02139, USA.}, Pages = {72-9}, Pii = {nn2017}, Pubmed = {18037883}, Title = {Development of hemodynamic responses and functional connectivity in rat somatosensory cortex}, Uuid = {B61F6E14-0EA6-48A5-9142-94BEACFFD3F2}, Volume = {11}, Year = {2008}, url = {papers/Colonnese_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn2017}} @article{Combs:1999, Abstract = {Microglial interaction with amyloid fibrils in the brains of Alzheimer's and prion disease patients results in the inflammatory activation of these cells. We observed that primary microglial cultures and the THP-1 monocytic cell line are stimulated by fibrillar beta-amyloid and prion peptides to activate identical tyrosine kinase-dependent inflammatory signal transduction cascades. The tyrosine kinases Lyn and Syk are activated by the fibrillar peptides and initiate a signaling cascade resulting in a transient release of intracellular calcium that results in the activation of classical PKC and the recently described calcium-sensitive tyrosine kinase PYK2. Activation of the MAP kinases ERK1 and ERK2 follows as a subsequent downstream signaling event. We demonstrate that PYK2 is positioned downstream of Lyn, Syk, and PKC. PKC is a necessary intermediate required for ERK activation. Importantly, the signaling response elicited by beta-amyloid and prion fibrils leads to the production of neurotoxic products. We have demonstrated in a tissue culture model that conditioned media from beta-amyloid- and prion-stimulated microglia or from THP-1 monocytes are neurotoxic to mouse cortical neurons. This toxicity can be ameliorated by treating THP-1 cells with specific enzyme inhibitors that target various components of the signal transduction pathway linked to the inflammatory responses.}, Author = {Combs, C. K. and Johnson, D. E. and Cannady, S. B. and Lehman, T. M. and Landreth, G. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Signal Transduction;Protein Kinase C;Neurotoxins;Enzyme Activation;Amyloid beta-Protein;Enzyme Precursors;Tyrosine;Animals;Cells, Cultured;src-Family Kinases;Microglia;Amyloid;Phosphorylation;Not relevant;Ca(2+)-Calmodulin Dependent Protein Kinase;11 Glia;Calcium;Peptide Fragments;Support, U.S. Gov't, P.H.S.;Mice;Prions;Intracellular Membranes;Protein-Tyrosine Kinase}, Medline = {99119437}, Month = {2}, Nlm_Id = {8102140}, Number = {3}, Organization = {Alzheimer Research Laboratory, Departments of Neurology and Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4928, USA.}, Pages = {928-39}, Pubmed = {9920656}, Title = {Identification of microglial signal transduction pathways mediating a neurotoxic response to amyloidogenic fragments of beta-amyloid and prion proteins}, Uuid = {6158C12B-0F22-4645-A708-B24421D117C1}, Volume = {19}, Year = {1999}, url = {papers/Combs_JNeurosci1999.pdf}} @article{Combs:2001, Abstract = {Reactive microglia associated with the beta-amyloid plaques in Alzheimer's disease (AD) brains initiate a sequence of inflammatory events integral to the disease process. We have observed that fibrillar beta-amyloid peptides activate a tyrosine kinase-based signaling response in primary mouse microglia and the human monocytic cell line, THP-1, resulting in production of neurotoxic secretory products, proinflammatory cytokines, and reactive oxygen species. We report that most of the amyloid-induced tyrosine kinase activity was stimulated after activation of Src family members such as Lyn. However, transduction of the signaling response required for increased production of the cytokines TNFalpha and IL1-beta was mediated by the nonreceptor tyrosine kinase, Syk. Additionally, beta-amyloid stimulated an NFkappaB-dependent pathway in parallel that was required for cytokine production. Importantly, TNFalpha generated by the monocytes and microglia was responsible for the majority of the neuorotoxic activity secreted by these cells after beta-amyloid stimulation but must act in concert with other factors elaborated by microglia to elicit neuronal death. Moreover, we observed that the neuronal loss was apoptotic in nature and involved increased neuronal expression of inducible nitric oxide synthase and subsequent peroxynitrite production. Selective inhibitors of inducible nitric oxide synthase effectively protected cells from toxicity associated with the microglial and monocytic secretory products. This study demonstrates a functional linkage between beta-amyloid-dependent activation of microglia and several characteristic markers of neuronal death occurring in Alzheimer's disease brains.}, Author = {Combs, C. K. and Karlo, J. C. and Kao, S. C. and Landreth, G. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Human;Tumor Necrosis Factor;Signal Transduction;Animals;Monocytes;Amyloid beta-Protein;Enzyme Precursors;Cells, Cultured;NF-kappa B;Transcription Factors;src-Family Kinases;Apoptosis;Microglia;Nitric-Oxide Synthase;Mice, Inbred C57BL;11 Glia;Not relevant;Support, Non-U.S. Gov't;Peptide Fragments;Alzheimer Disease;Neurons;Support, U.S. Gov't, P.H.S.;Mice;Inflammation;Protein-Tyrosine Kinase}, Medline = {21114081}, Month = {2}, Nlm_Id = {8102140}, Number = {4}, Organization = {Alzheimer Research Laboratory, Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.}, Pages = {1179-88}, Pii = {21/4/1179}, Pubmed = {11160388}, Title = {beta-Amyloid stimulation of microglia and monocytes results in TNFalpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis}, Uuid = {12F137BE-A9B3-4A7C-8517-95AFAC432C19}, Volume = {21}, Year = {2001}, url = {papers/Combs_JNeurosci2001.pdf}} @article{Compte:2003, Abstract = {Slow oscillatory activity (<1 Hz) is observed in vivo in the cortex during slow-wave sleep or under anesthesia and in vitro when the bath solution is chosen to more closely mimic cerebrospinal fluid. Here we present a biophysical network model for the slow oscillations observed in vitro that reproduces the single neuron behaviors and collective network firing patterns in control as well as under pharmacological manipulations. The membrane potential of a neuron oscillates slowly (at <1 Hz) between a down state and an up state; the up state is maintained by strong recurrent excitation balanced by inhibition, and the transition to the down state is due to a slow adaptation current (Na(+)-dependent K(+) current). Consistent with in vivo data, the input resistance of a model neuron, on average, is the largest at the end of the down state and the smallest during the initial phase of the up state. An activity wave is initiated by spontaneous spike discharges in a minority of neurons, and propagates across the network at a speed of 3-8 mm/s in control and 20-50 mm/s with inhibition block. Our work suggests that long-range excitatory patchy connections contribute significantly to this wave propagation. Finally, we show with this model that various known physiological effects of neuromodulation can switch the network to tonic firing, thus simulating a transition to the waking state.}, Author = {Compte, Albert and Sanchez-Vives, Maria V. and McCormick, David A. and Wang, Xiao-Jing J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Electrophysiology;Animals;Synapses;Neural Networks (Computer);Algorithms;Neural Conduction;Anesthesia;Kinetics;Pyramidal Cells;Ion Channels;research support, non-u.s. gov't;Sleep;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Cerebral Cortex;Membrane Potentials;Neurons;Interneurons;24 Pubmed search results 2008;Models, Neurological;Excitatory Postsynaptic Potentials}, Month = {5}, Nlm_Id = {0375404}, Number = {5}, Organization = {Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA. acompte\@umh.es}, Pages = {2707-25}, Pii = {00845.2002}, Pubmed = {12612051}, Title = {Cellular and network mechanisms of slow oscillatory activity (<1 Hz) and wave propagations in a cortical network model}, Uuid = {6E72A135-84ED-4D23-91C8-2B24580512E2}, Volume = {89}, Year = {2003}, url = {papers/Compte_JNeurophysiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00845.2002}} @article{Condeelis:2006, Abstract = {Macrophages within the tumor microenvironment facilitate angiogenesis and extracellular-matrix breakdown and remodeling and promote tumor cell motility. Recent studies reveal that direct communication between macrophages and tumor cells leads to invasion and egress of tumor cells into the blood vessels (intravasation). Thus, macrophages are at the center of the invasion microenvironment and are an important drug target for cancer therapy.}, Author = {Condeelis, John and Pollard, Jeffrey W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {0413066}, Number = {2}, Organization = {Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA. condeeli\@aecom.yu.edu}, Pages = {263-6}, Pii = {S0092-8674(06)00055-9}, Pubmed = {16439202}, Title = {Macrophages: obligate partners for tumor cell migration, invasion, and metastasis}, Uuid = {B67276BD-D36B-4702-A039-E339D50A1D40}, Volume = {124}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.01.007}} @article{Condes-Lara:2003, Abstract = {Interfascicular neurons (IFNs) of the anterior commissure (AC) include short-axon and projection types which receive inputs from commissural collaterals. Therefore, it was proposed that IFNs may play a role in processing nerve impulses arising from the forebrain and delivered by these collaterals [Brain Res. 931 (2002) 81-91]. To determine possible inputs from the forebrain to IFNs we performed extracellular recordings of 25 neurons from anesthetized adult rats. Short-latency evoked potentials in IFNs were elicited by electrical stimulation of the anterior olfactory, posterior amygdaloid nuclei (PA), and medial frontal cortex. The IFN responses showed three distinct patterns, namely, a single action potential (AP) followed by what appear to be spontaneous discharge; a burst of high-frequency APs, and a single AP followed by a period devoid of APs. The latter response which was elicited by stimulation of the PA, may be explained by an intervening inhibitory interneuron, perhaps GABAergic in nature. Finally, IFNs seem not to project back to any of these three forebrain areas, as we failed to demonstrate antidromic activation.}, Author = {Cond{\'e}s-Lara, Miguel and Paz, Carlos and Jim{\'e}nez, Javier Rodr{\'\i}guez and Mart{\'\i}nez, Gema and Mart{\'\i}nez-Lorenzana, Guadalupe and Larriva-Sahd, Jorge}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {24 Pubmed search results 2008;Olfactory Pathways;Septal Nuclei;Research Support, Non-U.S. Gov't;Rats, Sprague-Dawley;Action Potentials;Rats;Neural Pathways;Electrophysiology;Amygdala;Animals;Oligodendroglia;Male;Neurons;Frontal Lobe}, Medline = {22796348}, Month = {8}, Nlm_Id = {0045503}, Number = {2}, Organization = {Department of Developmental Biology and Neurophysiology, Instituto de Neurobiolog{\'\i}a, Universidad Nacional Aut{\'o}noma de M{\'e}xico, Campus UNAM-UAQ, Juriquilla, Apartado Postal 1-1141, Zona Centro, CP 76001 Quer{\'e}taro, Qro, Mexico.}, Pages = {288-92}, Pii = {S0006899303030543}, Pubmed = {12915264}, Title = {Electrophysiological responses of interfascicular neurons of the rat anterior commissure to activation from the anterior olfactory nucleus, medial frontal cortex, and posterior nucleus of the amygdala}, Uuid = {CDC3AEC8-9CAB-4B21-9B71-2F0EDFBA2F99}, Volume = {982}, Year = {2003}} @article{Condic:2001, Abstract = {In a variety of adult CNS injury models, embryonic neurons exhibit superior regenerative performance when compared with adult neurons. It is unknown how young neurons extend axons in the injured adult brain, in which adult neurons fail to regenerate. This study shows that cultured adult neurons do not adapt to conditions that are characteristic of the injured adult CNS: low levels of growth-promoting molecules and the presence of inhibitory proteoglycans. In contrast, young neurons readily adapt to these same conditions, and adaptation is accompanied by an increase in the expression of receptors for growth- promoting molecules (receptors of the integrin family). Surprisingly, the regenerative performance of adult neurons can be restored to that of young neurons by gene transfer-mediated expression of a single alpha- integrin.}, Author = {Condic, M. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci}, Keywords = {Fibronectins/metabolism/pharmacology;Cells, Cultured;Receptors, Fibronectin/biosynthesis/genetics;Rats;Transfection;Neurons, Afferent/cytology/drug effects/*metabolism;Adenoviridae/genetics;Animal;Laminin/metabolism/pharmacology;Cell Division/drug effects/genetics;Ganglia, Spinal/cytology/metabolism;Animals, Newborn;Nerve Regeneration/drug effects/*genetics;C;04 Adult neurogenesis factors;Integrins/*biosynthesis/*genetics;Support, U.S. Gov't, P.H.S.;*Transgenes;Aging/metabolism;Gene Expression;Ligands}, Number = {13}, Organization = {Department of Neurobiology and Anatomy, University of Utah School of Medicine, Salt Lake City, Utah 84132-0002, USA. maureen.condic\@hsc.utah.edu}, Pages = {4782-8.}, Title = {Adult neuronal regeneration induced by transgenic integrin expression}, Uuid = {5F2A9C4B-445F-4DFF-9C72-F832F4D69B64}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11425905%20http://www.jneurosci.org/cgi/content/full/21/13/4782%20http://www.jneurosci.org/cgi/content/abstract/21/13/4782}} @article{Connors:2004, Abstract = {Many neurons in the mammalian central nervous system communicate through electrical synapses, defined here as gap junction-mediated connections. Electrical synapses are reciprocal pathways for ionic current and small organic molecules. They are often strong enough to mediate close synchronization of subthreshold and spiking activity among clusters of neurons. The most thoroughly studied electrical synapses occur between excitatory projection neurons of the inferior olivary nucleus and between inhibitory interneurons of the neocortex, hippocampus, and thalamus. All these synapses require the gap junction protein connexin36 (Cx36) for robust electrical coupling. Cx36 appears to interconnect neurons exclusively, and it is expressed widely along the mammalian neuraxis, implying that there are undiscovered electrical synapses throughout the central nervous system. Some central neurons may be electrically coupled by other connexin types or by pannexins, a newly described family of gap junction proteins. Electrical synapses are a ubiquitous yet underappreciated feature of neural circuits in the mammalian brain.}, Author = {Connors, Barry W. and Long, Michael A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0147-006X}, Journal = {Annu Rev Neurosci}, Keywords = {Animals;Synapses;Humans;Rats;Neural Pathways;Brain;review;Cell Communication;Mammals;Connexins;Gap Junctions;research support, non-u.s. gov't;Action Potentials;research support, u.s. gov't, p.h.s.;Neurons;Mice;24 Pubmed search results 2008;Cats;Nerve Tissue Proteins}, Nlm_Id = {7804039}, Organization = {Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA. BWC\@Brown.edu}, Pages = {393-418}, Pubmed = {15217338}, Title = {Electrical synapses in the mammalian brain}, Uuid = {BF9D7BE9-ABB8-48A0-9647-1D7ECB6BCF79}, Volume = {27}, Year = {2004}, url = {papers/Connors_AnnuRevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.26.041002.131128}} @article{Connors:1996, Abstract = {Neurons generate diverse firing patterns to perform a range of specialized tasks. Experiments show that many features of these firing patterns arise from distinctive membrane properties, but theoretical work predicts that differences in neuronal morphology are also important.}, Author = {Connors, B. W. and Regehr, W. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {21 Neurophysiology;Models, Neurological;Animals;24 Pubmed search results 2008;Neurons;review}, Month = {12}, Nlm_Id = {9107782}, Number = {12}, Organization = {Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.}, Pages = {1560-2}, Pii = {S0960-9822(02)70771-9}, Pubmed = {8994812}, Title = {Neuronal firing: does function follow form?}, Uuid = {D7AAB44E-FD8D-4492-A1E3-E06661EA9866}, Volume = {6}, Year = {1996}} @article{Connors:1983, Abstract = {We have estimated the prevalence of coupling between neurons of the rat neocortex during postnatal development. Single intracellular injections of the fluorescent dye Lucifer Yellow CH resulted in dye coupling among 70\%of neurons from 1 to 4 days of age. Dye coupling dropped to 30 to 40\%by 10 to 18 days and occurred in 20\%of injected adult neurons. The number of neurons per dye-coupled aggregate also decreased. Whereas three to seven coupled neurons were common in cortex of 1 to 4 days, aggregates of more than two neurons were exceptionally rare in adults. The frequency of dye coupling did not vary systematically with cortical depth at any age. When chemical synaptic activity was blocked, most 4-day neurons exhibited short latency antidromically evoked depolarizations which were relatively insensitive to repetitive activation and membrane polarization. These depolarizations may represent electrotonically conducted spikes from coupled neurons. No such potentials were found in adult neurons. The results suggest that neuronal coupling is extensive in immature rat neocortex, but that coupling declines at a time just before the numbers of chemical synapses increase most rapidly.}, Author = {Connors, B. W. and Benardo, L. S. and Prince, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Aging;Animals;10 Development;Axonal Transport;Rats;Fluorescent Dyes;In Vitro;Evoked Potentials;Support, U.S. Gov't, P.H.S.;Manganese;Support, Non-U.S. Gov't;Isoquinolines;Rats, Inbred Strains;Neurons;Cerebral Cortex}, Medline = {83163356}, Month = {4}, Nlm_Id = {8102140}, Number = {4}, Pages = {773-82}, Pubmed = {6187902}, Title = {Coupling between neurons of the developing rat neocortex}, Uuid = {E941EEF8-9C71-4E87-838F-000A68214528}, Volume = {3}, Year = {1983}, url = {papers/Connors_JNeurosci1983.pdf}} @article{Connors:1984, Abstract = {Among neocortical astrocytes and neurons, intracellular injection of the fluorescent dye Lucifer Yellow CH into single cells will often label multiple adjacent cells. It is possible that this intercellular dye movement occurs through gap junctions, which in several systems are sensitive to cytoplasmic acidification. In the present study we tested the effect of increased CO2 levels, a treatment expected to decrease intracellular pH (pHi), on the prevalence of glial and neuronal dye coupling in neocortical slices. When CO2 levels were raised to 40\%or 50\%, dye coupling among astrocytes was completely abolished. Under the same conditions, the prevalence of dye coupling among neocortical neurons of adult guinea pigs was significantly reduced to 18.7\%, compared to the control level of 32.3\%. Dye coupling among immature rat neocortical neurons, which normally occurs at relatively high rates, was not measurably affected by CO2 levels up to 50\%. The results suggest that coupling between cortical glia is very sensitive to cytoplasmic acidification. The relative insensitivity of neuronal coupling to CO2 may indicate either that the conductance of neuronal gap junctions is only weakly affected by pHi or that neuron-to-neuron dye passage occurs via other types of intercytoplasmic pathways.}, Author = {Connors, B. W. and Benardo, L. S. and Prince, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Male;Neurons;research support, u.s. gov't, p.h.s. ;Neuroglia;21 Neurophysiology;Female;Guinea Pigs;in vitro ;Rats;Fluorescent Dyes;21 Gap junctions;Animals;Isoquinolines;24 Pubmed search results 2008;Carbon Dioxide;Cerebral Cortex}, Month = {5}, Nlm_Id = {8102140}, Number = {5}, Pages = {1324-30}, Pubmed = {6427421}, Title = {Carbon dioxide sensitivity of dye coupling among glia and neurons of the neocortex}, Uuid = {B14DC48F-C284-460A-9652-8D4DBA8DCEEE}, Volume = {4}, Year = {1984}} @article{Connors:1986, Abstract = {The electrophysiological properties of neurons in the three-layered dorsal cortex of the turtle, Pseudemys scripta elegans, have been studied in vitro. Intracellular recordings suggested two distinct classes of neuronal behavior. Cell labeling with either Lucifer Yellow or horseradish peroxidase revealed that these behaviors correlated with the two morphological classes of cortical neurons: pyramidal cells and stellate cells. Examination of Golgi-stained neurons of dorsal cortex did not uncover any other obvious classes. Pyramidal cells had their somata in the cell layer, and extended several densely spined apical dendrites through the molecular layer to the pia. They also had spiny basilar dendrites directed through the subcellular layer toward the ependymal border. Physiologically, pyramidal cells had relatively prolonged action potentials that showed marked frequency adaptation during a sustained suprathreshold current pulse. Their most striking characteristic was a tendency to fire two discrete sizes of action potential, one small (mean = 34 mV) and of relatively low threshold, the other large (mean = 76 mV) and of higher threshold. We hypothesize that at least some small spikes arise from distal dendritic sites, whereas large spikes are somatically generated. Both spikes were tetrodotoxin-sensitive, although calcium-dependent electrogenesis occurred when potassium channels were blocked. In contrast to pyramidal cells, the somata of stellate cells were found in the molecular and subcellular zones. Their dendrites tended to be horizontally oriented and spine-free. Stellate cells had relatively brief action potentials, each of which was followed by a large but short-lasting undershoot of membrane potential. Stellate cells showed little or no spike frequency adaptation. Spike amplitudes were always relatively uniform and large (mean = 73 mV). Thus, in the dorsal cortex of turtles, the pyramidal cells, which are projection neurons, and stellate cells, which are local GABAergic inhibitory neurons, have distinctly different membrane characteristics. The physiological properties of the two types of turtle cortical neurons are very similar to their counterparts in cortical structures of the mammalian telencephalon.}, Author = {Connors, B. W. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Golgi Apparatus;Electrophysiology;Animals;Tetrodotoxin;Pyramidal Tracts;Research Support, U.S. Gov't, P.H.S.;Turtles;Action Potentials;Histocytochemistry;21 Neurophysiology;Stellate Ganglion;Membrane Potentials;Isoquinolines;Neurons;Horseradish Peroxidase;24 Pubmed search results 2008;Visual Cortex;Research Support, Non-U.S. Gov't}, Medline = {86114191}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Pages = {164-77}, Pubmed = {3944618}, Title = {Cellular physiology of the turtle visual cortex: distinctive properties of pyramidal and stellate neurons}, Uuid = {2DCA25B3-523B-4687-9132-A01E2047C383}, Volume = {6}, Year = {1986}} @article{Connors:1990, Abstract = {Neurons of the neocortex differ dramatically in the patterns of action potentials they generate in response to current steps. Regular-spiking cells adapt strongly during maintained stimuli, whereas fast-spiking cells can sustain very high firing frequencies with little or no adaptation. Intrinsically bursting cells generate clusters of spikes (bursts), either singly or repetitively. These physiological distinctions have morphological correlates. RS and IB cells can be either pyramidal neurons or spiny stellate cells, and thus constitute the excitatory cells of the cortex. FS cells are smooth or sparsely spiny non-pyramidal cells, and are likely to be GABAergic inhibitory interneurons. The different firing properties of neurons in neocortex contribute significantly to its network behavior. 0166-2236 Journal Article Review Review, Tutorial}, Author = {Connors, B. W. and Gutnick, M. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Trends Neurosci}, Keywords = {18 Classic Neuroanatomy Physiology;Cerebral Cortex/*physiology;Neural Inhibition;M;Evoked Potentials;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't}, Number = {3}, Organization = {Division of Biology and Medicine, Brown University, Providence, RI 02912.}, Pages = {99-104}, Pubmed = {1691879}, Title = {Intrinsic firing patterns of diverse neocortical neurons}, Uuid = {C1A83AC6-B196-4D4D-979D-B6851D51CAF7}, Volume = {13}, Year = {1990}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1691879}} @article{Conover:2000, Abstract = {The subventricular zone (SVZ) of the lateral ventricles, the largest remaining germinal zone of the adult mammalian brain, contains an extensive network of neuroblasts migrating rostrally to the olfactory bulb. Little is known about the endogenous proliferation signals for SVZ neural stem cells or guidance cues along the migration pathway. Here we show that the receptor tyrosine kinases EphB1-3 and EphA4 and their transmembrane ligands, ephrins-B2/3, are expressed by cells of the SVZ. Electron microscopy revealed ephrin-B ligands associated with SVZ astrocytes, which function as stem cells in this germinal zone. A three-day infusion of the ectodomain of either EphB2 or ephrin-B2 into the lateral ventricle disrupted migration of neuroblasts and increased cell proliferation. These results suggest that Eph/ephrin signaling is involved in the migration of neuroblasts in the adult SVZ and in either direct or indirect regulation of cell proliferation.}, Author = {Conover, J. C. and Doetsch, F. and Garcia-Verdugo, J. M. and Gale, N. W. and Yancopoulos, G. D. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Nat Neurosci}, Keywords = {Lateral Ventricles/drug effects/*metabolism;Receptor Protein-Tyrosine Kinases/*metabolism;02 Adult neurogenesis migration;Cell Movement/drug effects/*physiology;Human;B-18;Signal Transduction/drug effects/physiology;Animal;Cell Division/drug effects/physiology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Fetal Proteins/*metabolism;Membrane Proteins/*metabolism/pharmacology;Mice;Astrocytes/cytology/drug effects/*metabolism}, Number = {11}, Organization = {The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA. jcc\@jax.org}, Pages = {1091-7.}, Title = {Disruption of Eph/ephrin signaling affects migration and proliferation in the adult subventricular zone}, Uuid = {7F310AFC-04E9-4B6F-9438-DCFE7B128042}, Volume = {3}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11036265%20http://www.nature.com/cgi-taf/DynaPage.taf?file=/neuro/journal/v3/n11/full/nn1100_1091.html%20http://www.nature.com/cgi-taf/DynaPage.taf?file=/neuro/journal/v3/n11/abs/nn1100_1091.html}} @article{Cook:1978, Abstract = {Localized Wallerian degeneration was induced in cat optic nerves by the gentle scratching of the exposed retinas. At intervals ranging up to 103 days after operation, the cats were killed and microscopic examination of the optic nerves showed, in addition to axonal degeneration, the presence of both demyelinating and demyelinated normal axons. The tongues of oligodendroglial cytoplasm were still associated with these demyelinated axons. This phenomenon is considered to reflect a change in the homeostasis of the oligodendroglial cell imposed by degeneration of a few axons from a state of maintaining the myelin sheath to one of resorption from adjacent normal axons. No evidence for the involvement of microglia in this process was found. It is concluded also that oligodendrocytes alone can be responsible for the removal of myelin debris during Wallerian degeneragion. This observation may be important to the understanding of certain demyelinating diseases of the central nervous system.}, Author = {Cook, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Neuroglia;Wallerian Degeneration;Nerve Degeneration;Lipids;Cats;Myelin Sheath;Astrocytes;Not relevant;11 Glia;Optic Nerve;Animals;Oligodendroglia;Phagocytosis}, Medline = {79073355}, Nlm_Id = {7609829}, Number = {5}, Pages = {357-68}, Pubmed = {724091}, Title = {Primary demyelination in cat optic nerves associated with surgically induced axonal degeneration}, Uuid = {123A0A17-63F4-4CC9-B7A9-D6A323B513C9}, Volume = {4}, Year = {1978}} @article{Cooper:1986, Abstract = {Plant lectins were used to examine the disposition of glycosylated molecules in vibratome sections through the barrel subfield of mouse somatosensory cortex at selected times during postnatal development. The peroxidase conjugates of peanut agglutinin (PNA, specific for N-acetylgalactosamine), concanavalin A (specific for mannose), and wheat germ agglutinin (specific for N-acetylglucosamine and N-acetylneuraminic acid) were used to study lectin binding in aldehyde-fixed tissue sections of cortex. Following peroxidase cytochemistry and light microscopy, it was found that all three lectins bound in the region of the barrel subfield as early as postnatal day 3 (day of birth = postnatal day 1). The lectins bound to the prospective sides and/or septae of individual barrels in preference to the prospective hollows. This lectin demarcation of the barrel field occurred prior to the detection of this region with cresyl violet staining and was still demonstrable on postnatal day 6, when the individual barrels became discernible with cresyl violet. This suggests that the lectin binding material is present before the barrel field becomes a fully formed and organized region. A decrease in lectin affinity for binding sites in these tissue sections occurs during postnatal development (Cooper and Steindler: Soc. Neurosci. (Abstr.) 10: 43a, '84) and this study demonstrates that lectins do not delineate the barrel field of more mature animals (2-3 months old), whereas barrels can be detected with cresyl violet at this time. A preliminary electron microscope analysis of the postnatal day 6 somatosensory cortex demonstrates that the lectin PNA binds to elements of the forming neuropil and also to Golgi apparatus intermediate saccules in neuronal cells. The prospective barrel field can be detected with lectins during a critical period in development in which alterations can occur in the barrel field in response to peripheral deprivation (Jeanmonod et al: Neuroscience 6:1503-35, '81) and therefore we suggest that the glycans visualized with lectin-peroxidase conjugates denote possible candidates for molecules involved in shaping barrel structure. 0021-9967 Journal Article}, Author = {Cooper, N. G. and Steindler, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Comp Neurol}, Keywords = {16 Barrels;K abstr;Binding Sites;Somatosensory Cortex/*metabolism;Peanut Agglutinin;Mice, Inbred ICR;Concanavalin A/metabolism;Support, U.S. Gov't, P.H.S.;Animals, Newborn;Lectins/*metabolism;Animals;Wheat Germ Agglutinins;Support, Non-U.S. Gov't;Mice;Vibrissae}, Number = {2}, Pages = {157-69}, Pubmed = {3755448}, Title = {Lectins demarcate the barrel subfield in the somatosensory cortex of the early postnatal mouse}, Uuid = {71D090A0-A3BE-46E8-AF47-485F4A96AD1C}, Volume = {249}, Year = {1986}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3755448}} @article{Cooper-Kuhn:2002, Abstract = {Since the early 1960s, in vivo observations have shown the generation of new neurons from dividing precursor cells. Nevertheless, these experiments suffered from skepticism, suggesting that the prevailing labeling method, which incorporates tagged thymidine analogs, such as [3H]-thymidine or bromodeoxyuridine (BrdU), may not be detecting a proliferative event, but could rather mark DNA repair in postmitotic neurons. Even today many scientists outside the field are still skeptical, because the question of specificity for thymidine labeling has not been sufficiently answered. This current paper aims at evaluating the arguments that are used by proponents and skeptics of this method by (i) presenting histological evidence of specificity of BrdU labeling for neural stem cell/progenitor activity in the adult brain; (ii) validating and comparing BrdU labeling with other histological methods; and (iii) combining BrdU and labeling methods for apoptosis to argue against DNA repair being a major contribution of BrdU-positive cells. 0165-3806 Journal Article}, Author = {Cooper-Kuhn, C. M. and Kuhn, H. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Animals;Neurology/methods;Rats;Apoptosis/physiology;Neurons/*cytology;Cell Cycle/physiology;Fluorescent Antibody Technique;Brain/*cytology;Female;Rats, Wistar;Time Factors;Cell Aging/physiology;In Situ Nick-End Labeling;Cell Division;Microscopy, Electron;Bromodeoxyuridine;A both;*DNA Repair}, Number = {1-2}, Organization = {Department of Neurology, University of Regensburg, Universitaetsstrasse 84, Regensburg, Germany.}, Pages = {13-21}, Title = {Is it all DNA repair? Methodological considerations for detecting neurogenesis in the adult brain}, Uuid = {0688DF66-CDF1-11D9-B244-000D9346EC2A}, Volume = {134}, Year = {2002}, url = {papers/Cooper-Kuhn_BrainResDevBrainRes2002}} @article{Corbin:2001, Abstract = {During development of the mammalian telencephalon, cells migrate via diverse pathways to reach their final destinations. In the developing neocortex, projection neurons are generated from cells that migrate radially from the underlying ventricular zone. In contrast, subsets of cells that populate the ventral piriform cortex and olfactory bulb reach these sites by migrating long distances. Additionally, it has been recently established that cells migrate tangentially from the ventral ganglionic eminences to the developing cortex. These tangentially migrating cells are a significant source of cortical interneurons and possibly other cell types such as oligodendrocytes. Here we summarize the known routes of migration in the developing telencephalon, with a particular focus on tangential migration. We also review recent genetic and transplantation studies that have given greater insight into the understanding of these processes and the molecular cues that may guide these migrating cells.}, Author = {Corbin, J. G. and Nery, S. and Fishell, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:44 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Neurons;Cell Differentiation;10 Development;Telencephalon;Neuroglia;Human;Mammals;Stem Cells;review, tutorial;Body Patterning;Animals;Cell Movement;Nerve Growth Factors;review}, Medline = {21547541}, Month = {11}, Nlm_Id = {9809671}, Organization = {Developmental Genetics Program and the Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, New York, 10016, USA.}, Pages = {1177-82}, Pii = {nn749}, Pubmed = {11687827}, Title = {Telencephalic cells take a tangent: non-radial migration in the mammalian forebrain}, Uuid = {8E9AB044-3C79-49ED-8F62-DD73C98375B9}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Corbin_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn749}} @article{Corbo:2002, Abstract = {Doublecortin (DCX) is a microtubule-associated protein that is required for normal neocortical and hippocampal development in humans. Mutations in the X-linked human DCX gene cause gross neocortical disorganization (lissencephaly or "smooth brain") in hemizygous males, whereas heterozygous females show a mosaic phenotype with a normal cortex as well as a second band of misplaced (heterotopic) neurons beneath the cortex ("double cortex syndrome"). We created a mouse carrying a targeted mutation in the Dcx gene. Hemizygous male Dcx mice show severe postnatal lethality; the few that survive to adulthood are variably fertile. Dcx mutant mice show neocortical lamination that is largely indistinguishable from wild type and show normal patterns of neocortical neurogenesis and neuronal migration. In contrast, the hippocampus of both heterozygous females and hemizygous males shows disrupted lamination that is most severe in the CA3 region. Behavioral tests show defects in context and cued conditioned fear tests, suggesting that deficits in hippocampal learning accompany the abnormal cytoarchitecture. 1529-2401 Journal Article}, Author = {Corbo, J. C. and Deuel, T. A. and Long, J. M. and LaPorte, P. and Tsai, E. and Wynshaw-Boris, A. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {J Neurosci}, Keywords = {Motor Activity;Heterozygote;Hippocampus/abnormalities/pathology/*physiopathology;Gene Targeting;Animals;Fear;Memory;Mice, Mutant Strains;10 Development;Phenotype;10 Hippocampus;Female;Neocortex/abnormalities/pathology/*physiopathology;F pdf;Reaction Time;Disease Models, Animal;Behavior, Animal;Male;Crosses, Genetic;Neurons/metabolism/pathology;Neuropeptides/deficiency/genetics/*metabolism;Learning;Support, U.S. Gov't, P.H.S.;Mice;Fetal Viability;Microtubule-Associated Proteins/metabolism;Genes, Reporter;Nervous System Malformations/*metabolism/pathology}, Number = {17}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {7548-57}, Title = {Doublecortin is required in mice for lamination of the hippocampus but not the neocortex}, Uuid = {C2063D4B-DF58-4196-BAEE-2EB2A32353B1}, Volume = {22}, Year = {2002}, url = {papers/Corbo_JNeurosci2002.pdf}} @article{Cordery:1999, Abstract = {We are interested in similarities and conserved mechanisms in early development of the reptilian and mammalian thalamocortical connections. We set out to analyse connectivity in embryonic turtle brains (Pseudemys scripta elegans, between stages 17 and 25), by using carbocyanine dye tracing. From the earliest stages studied, labelling from dorsal and ventral thalamus revealed backlabelled cells among developing thalamic fibres within the lateral forebrain bundle and striatum, which had similar morphology to backlabelled internal capsule cells in embryonic rat (Molnar and Cordery, 1999). However, thalamic crystal placements did not label cells in the dorsal ventricular ridge (DVR) at any stage examined. Crystal placements into both dorsal and lateral cortex labelled cells in the DVR and, reciprocally, DVR crystal placements labelled cells in the dorsal and lateral cortices. Retrograde labelling revealed that thalamic fibres arrive in the DVR and dorsal cortex by stage 19. The DVR received projections from the nucleus rotundus and the dorsal cortex exclusively from the perirotundal complex (including lateral geniculate nucleus). Thalamic fibres show this remarkable degree of specificity from the earliest stage we could examine with selective retrograde labelling (stage 19). Our study demonstrates that axons of similar cells are among the first to reach dorsal and ventral thalamus in mammals and reptiles. Our connectional analysis in turtle suggests that some cells of the mammalian primitive internal capsule are homologous to a cell group within the reptilian lateral forebrain bundle and striatum and that diverse vertebrate brains might use a highly conserved pattern of early thalamocortical development. 0021-9967 Journal Article}, Author = {Cordery, P. and Molnar, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Comp Neurol}, Keywords = {*Brain Mapping;Corpus Striatum/physiology;Species Specificity;Neural Pathways/physiology;Fluorescent Dyes;Crystallization;Turtles/embryology/*physiology;Hypothalamus/physiology;Prosencephalon/physiology;N;Embryo, Nonmammalian/growth &development/*physiology;Animals;Support, Non-U.S. Gov't;Cerebral Cortex/embryology/*physiology;19 Neocortical evolution;Thalamus/embryology/*physiology}, Number = {1}, Organization = {University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, United Kingdom.}, Pages = {26-54}, Pubmed = {10464368}, Title = {Embryonic development of connections in turtle pallium}, Uuid = {8AC2FF84-5DE4-4774-AC22-A38D99826360}, Volume = {413}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10464368}} @article{Corlew:2004, Abstract = {Spontaneous [Ca2+]i transients were measured in the mouse neocortex from embryonic day 16 (E16) to postnatal day 6 (P6). On the day of birth (P0), cortical neurones generated widespread, highly synchronous [Ca2+]i transients over large areas. On average, 52\%of neurones participated in these transients, and in 20\%of slices, an average of 80\%participated. These transients were blocked by TTX and nifedipine, indicating that they resulted from Ca2+ influx during electrical activity, and occurred at a mean frequency of 0.91 min(-1). The occurrence of this activity was highly centred at P0: at E16 and P2 an average of only 15\%and 24\%of neurones, respectively, participated in synchronous transients, and they occurred at much lower frequencies at both E16 and P2 than at P0. The overall frequency of [Ca2+]i transients in individual cells did not change between E16 and P2, just the degree of their synchronicity. The onset of this spontaneous, synchronous activity correlated with a large increase in Na+ current density that occurred just before P0, and its cessation with a large decrease in resting resistance that occurred just after P2. This widespread, synchronous activity may serve a variety of functions in the neonatal nervous system.}, Author = {Corlew, Rebekah and Bosma, Martha M. and Moody, William J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 03:08:34 +0000}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Electrophysiology;Animals;Osmolar Concentration;Aging;research support, u.s. gov't, p.h.s. ;research support, u.s. gov't, non-p.h.s. ;Reaction Time;Embryonic Development;Calcium;Embryo;research support, non-u.s. gov't ;Animals, Newborn;Cerebral Cortex;21 Neurophysiology;Neurons;21 Cortical oscillations;Intracellular Membranes;Tetraethylammonium;Spontaneous activity;21 Activity-development;Neocortex;calcium imaging;optical physiology;optical imaging;in vitro;Mice; currOpinRvw}, Month = {10}, Nlm_Id = {0266262}, Number = {Pt 2}, Organization = {Department of Biology, University of Washington, Seattle, WA 98115, USA.}, Pages = {377-90}, Pii = {jphysiol.2004.071621}, Pubmed = {15297578}, Title = {Spontaneous, synchronous electrical activity in neonatal mouse cortical neurones}, Uuid = {9BEDDF05-C5DE-4D06-82F3-6A1767021255}, Volume = {560}, Year = {2004}, url = {papers/Corlew_JPhysiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2004.071621}} @article{Coronas:2002, Abstract = {Previous experiments have established that grafts of embryonic day (E) 16 frontal cortex placed into the occipital cortex of postnatal day (P) 0-P1 rats selectively attract axons from the ventrolateral and ventromedial (VL/VM) thalamic nuclei (Frapp{\'e} et al., Exp. Neurol. 169 (2001) 264). The present study was therefore undertaken to identify any possible maturation-promoting activity of the cortex on VL/VM thalamic cells. In a first step, a primary culture of VL/VM thalamic cells taken from P0-P1 rats was developed. Neurons, glial cells and a few immature, nestin immunoreactive cells were identified in the culture. In a second step, VL/VM thalamic cells that had been maintained in vitro for 4-5 days were cultured for 7 additional days in isolation (control condition) or with an E16 or P5 explant of frontal or occipital cortex placed on a microporous membrane. In control conditions, the total cell population and the percentage of MAP-2 immunoreactive neurons were not modified with time. In contrast, the percentage of MAP-2 immunoreactive neurons was increased in E16 cortex co-cultures whereas the total cell population was unchanged and the proliferative activity remained very low. Also, the mean number of neurites per neuron was increased but no effect was found on neuritic length. Similar effects on neuronal maturation were found with E16 frontal or occipital cortex explants, indicating a lack of areal specificity. P5 cortex also produced, but to a lesser extent, an increase in percentage of MAP-2 immunoreactive neurons. Further, P5 cortex had no effect on mean number of neurites per neuron but substantially promoted elongation of neuronal processes. We propose that in addition to their well-established survival promoting effect, diffusible molecules released by embryonic and early postnatal cortex can promote in vitro the maturation of thalamic neurons.}, Author = {Coronas, Val{\'e}rie and Arnault, Patricia and Roger, Michel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Microtubule-Associated Proteins;Cell Differentiation;Animals;Pregnancy;Cells, Cultured;Coculture Techniques;Rats;Neural Pathways;Frontal Lobe;Female;Cell Communication;Neurites;Rats, Wistar;Animals, Newborn;Thalamus;Cerebral Cortex;Neurons;Occipital Lobe;Body Patterning;Cell Division;24 Pubmed search results 2008;Immunohistochemistry;Diffusion;Growth Substances}, Medline = {22070432}, Month = {5}, Nlm_Id = {8500749}, Number = {1}, Organization = {CNRS-UMR 6558, Laboratoire des Biomembranes et Signalisation Cellulaire, Universit{\'e} de Poitiers, Facult{\'e} des Sciences, Poitiers, France. valerie.coronas\@univ-poitiers.fr}, Pages = {57-67}, Pii = {S0168010202000202}, Pubmed = {12074841}, Title = {Cortical diffusible factors increase MAP-2 immunoreactive neuronal population in thalamic cultures}, Uuid = {55D37F41-652C-4379-A566-047270D1E02A}, Volume = {43}, Year = {2002}} @article{Corotto:1993, Abstract = {Neurogenesis of olfactory bulb granule cells is known to persist in adult rats where, in some strains, the bulbs grow throughout life. In mice, bulb growth ceases early in adulthood and here we ask if granule cell neurogenesis persists after the bulbs have stopped growing. By injecting adult mice with bromodeoxyuridine (BrdU) and allowing short and long survival times, we found that new cells form in the subependymal layer and that they migrate subsequently into the olfactory bulbs where they acquire the nuclear morphology of granule cells and express neuron-specific markers. Using [3H]thymidine, we found that most of these adult-generated granule neurons persist within the bulbs for at least 16 weeks. This shows the persistence of neurogenesis and neuronal migration in adult animals in which the olfactory bulbs have stopped growing.}, Author = {Corotto, F. S. and Henegar, J. A. and Maruniak, J. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Neurosci Lett}, Keywords = {Neurons/*physiology;02 Adult neurogenesis migration;Cell Differentiation;Olfactory Bulb/cytology/growth &development;Cell Survival/physiology;Female;Immunohistochemistry;03 Adult neurogenesis progenitor source;Thymidine/metabolism;Bromodeoxyuridine/pharmacology;Cytoplasmic Granules/ultrastructure;Calcium-Binding Protein, Vitamin D-Dependent/immunology/metabolism;Animal;BB;Brain/anatomy &histology/cytology/*growth &development;Mice}, Number = {2}, Organization = {Division of Biological Sciences, University of Missouri, Columbia 65211.}, Pages = {111-4.}, Title = {Neurogenesis persists in the subependymal layer of the adult mouse brain}, Uuid = {69B14899-B1BF-483C-9C23-E0088B22B32D}, Volume = {149}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8474679}} @article{Corral:2001, Abstract = {Embryologists have long used morphological characteristics, and more recently marker genes, to identify neural tissue and to test the neural- inducing activity of specific cell populations and signalling molecules. These markers are also used to assess the function(s) of neural genes themselves. Progression from neural induction to terminal differentiation of neurons is a multistep process, and each step involves the activation and/or repression of genes that can be used as molecular markers for these different events. Here we briefly review these key steps in neurogenesis within the vertebrate central nervous system, and evaluate the markers used to define them. We emphasize the importance of cellular context and an understanding of gene function for interpreting the significance of marker genes.}, Author = {Corral, R. D. and Storey, K. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {10 Development;F pdf}, Number = {11}, Organization = {Kate G. Storey and Ruth Diez del Corral are both at the Division of Cell and Developmental Biology, Wellcome Trust Building, University of Dundee, Dow Street, Dundee DD1 5EH, UK.}, Pages = {835-9.}, Title = {Markers in vertebrate neurogenesis}, Uuid = {A50ED16D-C2C2-43D8-9D95-638346F4DE4A}, Volume = {2}, Year = {2001}, url = {papers/Corral_NatRevNeurosci2001.pdf}} @article{Corti:2002, Abstract = {The aim of the present study is to determine whether the expansion and mobilization of circulating bone marrow (BM) stem cells by in vivo treatment with granulocyte-colony stimulating factor (G-CSF) and stem cell factor (SCF) increase the amount of BM-derived neuronal cells in mouse brain. The presence of BM-derived cells in the brain was traced by transplanting into lethally irradiated adults and newborns adult BM from transgenic mice that ubiquitously expressed enhanced green fluorescent protein (GFP). GFP+ and Y-chromosome+ donor-derived cells were present in several brain areas of all treated mice (cortical and subcortical areas, cerebellum, olfactory bulb). The presence of GFP+ cells expressing nuclear neural specific antigen (NeuN), neurofilament, and beta-III tubulin in cortical forebrain and olfactory bulb (OB) was higher in G-CSF-SCF treated groups (P <0.05, analysis of variance, Fisher post hoc). We observed that overall the amount of double positive cells was higher in animals treated at birth than in adults and in OB than in forebrain areas (P <0.05). Temporal cortical areas of cytokine-treated adult animals revealed a mean threefold increase in the number of GFP+ cells expressing the nuclear neural specific antigen (211 +/- 86 GFP+NeuN+/mm(3) in G-CSF + SCF treated mice and 66 +/- 33 GFP+NeuN+/mm(3) in control animals). GFP+ cells coexpressing neuronal markers contain only one nucleus and have a DNA index (a measure of DNA ploidy) identical to that of surrounding neurons, thus excluding donor cell fusion with endogenous cells as a relevant phenomenon under these experimental conditions. Our results indicate that G-CSF and SCF administration modulates the availability of GFP+ cells in the brain and enhances their capacity to acquire neuronal characteristics. Cytokine stimulation of autologous stem cells might be seen as a new strategy for neuronal repair in neurodegenerative diseases.}, Author = {Corti, S. and Locatelli, F. and Strazzer, S. and Salani, S. and Del Bo, R. and Soligo, D. and Bossolasco, P. and Bresolin, N. and Scarlato, G. and Comi, G. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cytokines;Cell Differentiation;Animals;Bone Marrow Transplantation;Brain;Antigens, Differentiation;Female;Cell Count;Mice, Transgenic;Granulocyte Colony-Stimulating Factor;Mice, Inbred C57BL;11 Glia;Cell Movement;Male;Bone Marrow Cells;Animals, Newborn;Neurons;Age Factors;Mice;Stem Cell Factor;Luminescent Proteins;Y Chromosome;Stem Cells;Genes, Reporter;Research Support, Non-U.S. Gov't}, Medline = {22316816}, Month = {10}, Nlm_Id = {0370712}, Number = {2}, Organization = {Centro Dino Ferrari, Dipartimento di Scienze Neurologiche, Universit\`{a} degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, 20122, Milan, Italy.}, Pages = {443-52}, Pii = {S0014488602980040}, Pubmed = {12429190}, Title = {Modulated generation of neuronal cells from bone marrow by expansion and mobilization of circulating stem cells with in vivo cytokine treatment}, Uuid = {0A7E0CD4-D220-42EA-9CD3-F13E52734429}, Volume = {177}, Year = {2002}} @article{Corti:2002a, Abstract = {There is now evidence that bone marrow (BM) can generate cells expressing neuronal antigens in adult mouse brain. In the present study, we examined the spinal cord and dorsal root ganglia (DRG) of adult mice 3 months after BM cell transplantation from transgenic donor mice expressing the enhanced green fluorescent protein (GFP). To determine whether GFP(+) cells acquire neuroectodermal phenotypes, we tested, by immunocytochemistry followed by confocal analysis, the coexpression of the astrocytic marker glial fibrillary acidic protein (GFAP) and the neuronal markers NeuN, neurofilament (NF), and class III beta-tubulin (TuJ1). Rare GFP(+) cells coexpressing TuJ1, NF, and NeuN were found both in spinal cord and in sensory ganglia. These cells have small dimensions and short cytoplasmic processes, probably reflecting an immature phenotype. Double GFP and GFAP positivity was found only in spinal cord. To determine whether cell fusion with endogenous cells occurred, we investigated the nuclear content of cells coexpressing GFP and neuronal or astrocytic markers, demonstrating that these cells have only one nucleus and a DNA ploidy that it is not different from that of surrounding neurons and astrocytes. Large numbers of GFP(+) cells are also positively stained for F4/80, a microglial-recognizing antibody, and present a characteristic microglial-like morphology both in spinal cord and, with a higher frequency, in sensory ganglia. These data support a potential role for BM-derived stem cells in spinal cord neuroneogenesis. They also confirm that the microglial compartment within the CNS and in DRG undergoes a relatively fast turnover, with the contribution of hematopoietic stem cells. Both these findings might prove useful for the development of treatments for spinal cord neurodegenerative and acquired disorders.}, Author = {Corti, S. and Locatelli, F. and Donadoni, C. and Strazzer, S. and Salani, S. and Del Bo, R. and Caccialanza, M. and Bresolin, N. and Scarlato, G. and Comi, G. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Glial Fibrillary Acidic Protein;Cell Differentiation;Animals;Stem Cell Transplantation;Ectoderm;Ganglia, Spinal;Bone Marrow Transplantation;Microscopy, Confocal;Microglia;Mice, Transgenic;11 Glia;Green Fluorescent Proteins;Male;Spinal Cord;Bone Marrow Cells;Neurons;Mice;Immunohistochemistry;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22331219}, Month = {12}, Nlm_Id = {7600111}, Number = {6}, Organization = {Centro Dino Ferrari, Dipartimento di Scienze Neurologiche, Universit\`{a} degli Studi di Milano, IRCCS Ospedale Maggiore Policlinico, Milano, Italy. stcorti\@yahoo.it}, Pages = {721-33}, Pubmed = {12444594}, Title = {Neuroectodermal and microglial differentiation of bone marrow cells in the mouse spinal cord and sensory ganglia}, Uuid = {2D57F590-D3B1-11D9-A0E9-000D9346EC2A}, Volume = {70}, Year = {2002}, url = {papers/Corti_JNeurosciRes2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10455}} @article{Corvetti:2005, Abstract = {Chondroitin sulfate proteoglycans are major constituents of the extracellular matrix and form perineuronal nets. Information regarding the growth-inhibitory activity of these molecules after injury is rapidly expanding. However, less is known about their physiological role in the adult undamaged CNS. Here, we investigated the function of chondroitin sulfate proteoglycans in maintaining the proper structure of Purkinje axons in the cerebellum of adult rats. To this end, we examined the morphology and distribution of intracortical Purkinje neurites after intraparenchymal injection of chondroitinase ABC. Staining with the lectin Wisteria floribunda agglutinin or 2B6 antibodies showed that this treatment efficiently removed chondroitin sulfate proteoglycans from wide areas of the cerebellar cortex. In the same sites, there was a profuse outgrowth of terminal branches from the Purkinje infraganglionic plexus, which invaded the deeper regions of the granular layer. In contrast, myelinated axon segments were not affected and maintained their normal relationship with oligodendroglial sheaths. Purkinje axon sprouting was first evident at 4 d and increased further at 7 d after enzyme application. Within 42 d, the expression pattern of chondroitin sulfate proteoglycans gradually recovered, whereas axonal modifications progressively regressed. Our results show that, in the absence of injury or novel external stimuli, degradation of chondroitin sulfate proteoglycans is sufficient to induce Purkinje axon sprouting but not the formation of long-lasting synaptic contacts. Together with other growth-inhibitory molecules, such as myelin-associated proteins, chondroitin sulfate proteoglycans restrict structural plasticity of intact Purkinje axons to maintain normal wiring patterns in the adult cerebellar cortex.}, Author = {Corvetti, Luigi and Rossi, Ferdinando}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;11 Glia;10 Structural plasticity;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {31}, Organization = {Department of Neuroscience, Rita Levi Montalcini Center for Brain Repair, University of Turin, I-10125 Turin, Italy. luigi.corvetti\@unito.it}, Pages = {7150-8}, Pii = {25/31/7150}, Pubmed = {16079397}, Title = {Degradation of chondroitin sulfate proteoglycans induces sprouting of intact purkinje axons in the cerebellum of the adult rat}, Uuid = {EC668BA2-4CD0-4B9A-9C8A-3B88CF2E44BF}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0683-05.2005}} @article{Coskun:2001, Abstract = {Bone morphogenetic proteins (BMPs), a group of cytokines in the TGF- beta superfamily, have complex regulatory roles in the control of neural proliferation and cell fate decision. In this study, we analyzed the potential role(s) of BMP signaling on the regulation of the proliferation and differentiation of the unique progenitor cells of the neonatal anterior subventricular zone (SVZa). Unlike other progenitor cells of the brain, SVZa progenitor cells have the capacity to divide even though they express a neuronal phenotype. In order to augment or inhibit endogenous BMP signaling, we injected into the neonatal rat SVZa replication-deficient retroviruses encoding for either the wild- type BMP receptor subtype Ia (wt-BMPR-Ia) or a mutated dominant- negative version of BMPR-Ia (dn-BMPR-Ia) in conjunction with a reporter gene, human alkaline phosphatase (AP) and perfused the pups 1, 4 and 7 days post injection. We analyzed whether changing the expression of BMPR-Ia has an effect on the spatial-temporal expression pattern of the cyclin dependent kinase inhibitor, p19(INK4d), or on the phenotype of SVZa derived cells. The results of our study confirmed and extended our previous findings that in control (non injected) animals, the rostral migratory stream (RMS), traversed by the SVZa-derived cells en route to the olfactory bulb, exhibits an anterior(high)-posterior(low) gradient of p19(INK4d) expression; p19(INK4d) expression is essentially absent in the SVZa and highest in the subependymal zone in the middle of the olfactory bulb. However, SVZa progenitor cells encoding the wt-BMPR-Ia gene express p19(INK4d) within the SVZa, suggesting that the BMPs induce SVZa cells to ectopically undergo cell cycle exit within the SVZa. Furthermore, unlike striatal SVZ progenitor cells, which acquire an astrocytic phenotype when exposed to BMPs, SVZa progenitor cells retain their neuronal commitment under augmented BMP signaling.}, Author = {Coskun, V. and Venkatraman, G. and Yang, H. and Rao, M. S. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Int J Dev Neurosci}, Keywords = {Human;Cell Differentiation;Genetic Vectors/genetics;Recombinant Fusion Proteins/biosynthesis/genetics;Transfection;Rats;Receptors, Growth Factor/genetics/*physiology;Olfactory Bulb/*cytology/embryology;Alkaline Phosphatase/biosynthesis/genetics;Cell Movement;Animal;Protein-Serine-Threonine Kinases/genetics/*physiology;Cerebral Ventricles/embryology;Bone Morphogenetic Proteins/*physiology;Animals, Newborn;Neurons, Afferent/*cytology;Morphogenesis;Defective Viruses/genetics;Cell Lineage;C;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Retroviridae/genetics;Carrier Proteins/*biosynthesis/genetics;Genes, Reporter;*Gene Expression Regulation}, Number = {2}, Organization = {Department of Cell Biology, Emory University School of Medicine, 1648 Pierce Drive, Atlanta, GA 30322, USA.}, Pages = {219-27.}, Title = {Retroviral manipulation of the expression of bone morphogenetic protein receptor Ia by SVZa progenitor cells leads to changes in their p19(INK4d) expression but not in their neuronal commitment}, Uuid = {BD0149DF-395B-466B-92C3-7723A276A87E}, Volume = {19}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11255035}} @article{Coskun:2001a, Abstract = {In this study we investigated whether the pattern of expression of the cyclin-dependent kinase inhibitor p19(INK4d) by the unique progenitor cells of the neonatal anterior subventricular zone (SVZa) can account for their ability to divide even though they express phenotypic characteristics of differentiated neurons. p19(INK4d) was chosen for analysis because it usually acts to block permanently the cell cycle at the G(1) phase. p19(INK4d) immunoreactivity and the incorporation of bromodeoxyuridine (BrdU) by SVZa cells were compared with that of the more typical progenitor cells of the prenatal telencephalic ventricular zone. In the developing telencephalon, p19(INK4d) is expressed by postmitotic cells and has a characteristic perinuclear distribution depending on the laminar position and state of differentiation of a cell. Moreover, the laminar-specific staining of the developing cerebral cortex revealed that the ventricular zone (VZ) is divided into p19(INK4d)(+) and p19(INK4d)(-) sublaminae, indicating that the VZ has a previously unrecognized level of functional organization. Furthermore, the rostral migratory stream, traversed by the SVZa- derived cells, exhibits an anterior(high)-posterior(low) gradient of p19(INK4d) expression. On the basis of the p19(INK4d) immunoreactivity and BrdU incorporation, SVZa-derived cells appear to exit and reenter the cell cycle successively. Thus, in contrast to telencephalic VZ cells, SVZa cells continue to undergo multiple rounds of division and differentiation before becoming postmitotic.}, Author = {Coskun, V. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {J Neurosci}, Keywords = {Cell Differentiation/genetics;Carrier Proteins/*biosynthesis;Rats;Telencephalon/cytology/embryology/*metabolism;Cell Cycle;*Gene Expression Regulation, Developmental;Animal;Cell Movement;Rats, Sprague-Dawley;Enzyme Inhibitors/pharmacology;Stem Cells/cytology/*metabolism;Animals, Newborn;Cell Division/genetics;Cell Lineage;Cyclin-Dependent Kinases/antagonists &inhibitors;C;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Neurons/cytology/metabolism;Cerebral Cortex/cytology/embryology/metabolism;Cerebral Ventricles/cytology/embryology/metabolism;Bromodeoxyuridine}, Number = {9}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.}, Pages = {3092-103.}, Title = {The expression pattern of the cell cycle inhibitor p19(INK4d) by progenitor cells of the rat embryonic telencephalon and neonatal anterior subventricular zone}, Uuid = {57686C2E-DF32-45CB-A205-F5B6754A631A}, Volume = {21}, Year = {2001}, url = {papers/Coskun_JNeurosci2001}} @article{Coskun:2002, Abstract = {An overriding principle of development is that neurons become permanently postmitotic once they initiate differentiation. Work in our laboratory, however, has provided evidence for a population of progenitor cells in mammalian forebrain that express properties of differentiated neurons, even though they continue to divide. These neuronal progenitor cells are situated in the rostral migratory stream (RMS), which extends from a specialized portion of the subventricular zone surrounding the anterior tip of the lateral ventricle, referred to as the SVZa, to the middle of the olfactory bulb. As SVZa-derived cells migrate to the olfactory bulb, they undergo cell division, and they never deviate from the RMS. Once they reach their final destinations, they become terminally postmitotic interneurons. This Mini-Review concerns findings from our recent experiments designed to reveal the intrinsic and extrinsic mechanisms governing the proliferation and differentiation of the unique SVZa neuronal progenitor cells. We have investigated the role(s) of cell cycle regulatory proteins, in particular, the cell cycle inhibitor p19(INK4d), in the control of SVZa cell proliferation. Several studies have indicated that cells withdraw from the cell cycle once they express p19(INK4d). To begin to investigate whether p19(INK4d)(+) SVZa-derived cells are postmitotic, we analyzed the pattern of p19(INK4d) expression by the cells of the RMS. A pronounced gradient of p19(INK4d) expression was demonstrated; progressively more cells are p19(INK4d) immunoreactive as the olfactory bulb is approached. In addition, the capacity of p19(INK4d)(+) cells to incorporate bromodeoxyuridine was investigated. From the results of these studies, we conclude that SVZa cells in the RMS can successively down-regulate their expression of p19(INK4d) as they migrate and that they repeatedly exit and reenter the cell cycle while en route to the olfactory bulb. These studies led us to investigate whether bone morphogenetic proteins (BMPs) are involved in the regulation of SVZa cell proliferation and p19(INK4d) expression, because, elsewhere in the CNS, BMPs modulate cell proliferation and influence cell fate decisions. To determine the effects of BMP signaling on SVZa cell proliferation and differentiation, we altered the expression of the BMP receptor Ia (BMPR-Ia) using retrovirally mediated gene transfer. The cells in the SVZa encoding the wild-type BMPR-Ia exit the cell cycle and do not appear to migrate through the RMS. Conversely, both within the SVZa and along the RMS, the majority of SVZa-derived cells encoding a dominant-negative BMPR-Ia gene do not express p19(INK4d). These findings indicate that p19(INK4d) expression is suppressed when BMP signaling is inhibited. Furthermore, SVZa-derived cells with both augmented and inhibited BMP signaling retain their neuronal commitment. Collectively, these studies have revealed that SVZa cell proliferation and differentiation is under the control of several interacting intrinsic and extrinsic factors.}, Author = {Coskun, Volkan and Luskin, Marla B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Rodentia;02 Adult neurogenesis migration;Cell Differentiation;03 Adult neurogenesis progenitor source;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Cell Division;Animals;Brain;Cell Movement;Neurons;review}, Medline = {22194568}, Month = {9}, Nlm_Id = {7600111}, Number = {6}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.}, Pages = {795-802}, Pubmed = {12205673}, Title = {Intrinsic and extrinsic regulation of the proliferation and differentiation of cells in the rodent rostral migratory stream}, Uuid = {B67306E0-6850-4BE3-B0AB-614623359CAD}, Volume = {69}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10336}} @article{Cossart:2005, Abstract = {Studies relating spontaneous network activities to cognitive processes and/or brain disorders constitute a recently expanding field of investigation. They are mostly based either on cellular recordings--usually performed in pharmacologically induced oscillations in brain slices--or on multi-cellular recordings using tetrodes or multiple electrodes. However, these research strategies cannot link the electrical recordings with morphological characterization of the neurons. The progress made in imaging techniques allows for the first time to have simultaneously a dynamic and global characterization of network activity and to determine the single-cell properties of the unitary microcircuits involved in this activity.}, Author = {Cossart, Rosa and Ikegaya, Yuji and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0143-4160}, Journal = {Cell Calcium}, Keywords = {21 Neurophysiology;Action Potentials;Neural Pathways;21 Calcium imaging;Calcium;Sodium;Animals;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8006226}, Number = {5}, Organization = {INMED, INSERM U29, Parc Scientifique de Luminy, BP.13, 13273 Marseille, Cedex 9, France.}, Pages = {451-7}, Pii = {S0143-4160(05)00030-8}, Pubmed = {15820393}, Title = {Calcium imaging of cortical networks dynamics}, Uuid = {AAD63EAA-0144-11DB-9E68-000D9346EC2A}, Volume = {37}, Year = {2005}, url = {papers/Cossart_CellCalcium2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ceca.2005.01.013}} @article{Cossart:2006, Abstract = {GABAergic interneurons play diverse and important roles in controlling neuronal network dynamics. They are characterized by an extreme heterogeneity morphologically, neurochemically, and physiologically, but a functionally relevant classification is still lacking. Present taxonomy is essentially based on their postsynaptic targets, but a physiological counterpart to this classification has not yet been determined. Using a quantitative analysis based on multidimensional clustering of morphological and physiological variables, we now demonstrate a strong correlation between the kinetics of glutamate and GABA miniature synaptic currents received by CA1 hippocampal interneurons and the laminar distribution of their axons: neurons that project to the same layer(s) receive synaptic inputs with similar kinetics distributions. In contrast, the kinetics distributions of GABAergic and glutamatergic synaptic events received by a given interneuron do not depend upon its somatic location or dendritic arborization. Although the mechanisms responsible for this unexpected observation are still unclear, our results suggest that interneurons may be programmed to receive synaptic currents with specific temporal dynamics depending on their targets and the local networks in which they operate.}, Author = {Cossart, Rosa and Petanjek, Zdravko and Dumitriu, Dani and Hirsch, June C. and Ben-Ari, Yehezkel and Esclapez, Monique and Bernard, Christophe}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1050-9631}, Journal = {Hippocampus}, Keywords = {Research Support, Non-U.S. Gov't;Excitatory Amino Acid Antagonists;gamma-Aminobutyric Acid;Animals;Rats;Neural Pathways;Glutamic Acid;Synaptic Transmission;Patch-Clamp Techniques;21 Epilepsy;Neurotransmitter Agents;Reaction Time;Hippocampus;Rats, Wistar;Organ Culture Techniques;Axons;Time Factors;Dendrites;Receptors, GABA-A;Nerve Net;Animals, Newborn;21 Neurophysiology;Cell Shape;GABA Antagonists;Interneurons;24 Pubmed search results 2008;Neural Inhibition;Excitatory Postsynaptic Potentials}, Nlm_Id = {9108167}, Number = {4}, Organization = {INMED, INSERM U29, Parc scientifique de Luminy, B.P 13, 13673 Marseille, C{\'e}dex 9, France.}, Pages = {408-20}, Pubmed = {16435315}, Title = {Interneurons targeting similar layers receive synaptic inputs with similar kinetics}, Uuid = {DDED4491-6F1B-4C33-9045-DF9EEAD5B9A6}, Volume = {16}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/hipo.20169}} @article{Cossart:2001, Abstract = {Impaired inhibition is thought to be important in temporal lobe epilepsy (TLE), the most common form of epilepsy in adult patients. We report that, in experimental TLE, spontaneous GABAergic inhibition was increased in the soma but reduced in the dendrites of pyramidal neurons. The former resulted from the hyperactivity of somatic projecting interneurons, whereas the latter was probably due to the degeneration of a subpopulation of dendritic projecting interneurons. A deficit in dendritic inhibition could reduce seizure threshold, whereas enhanced somatic inhibition would prevent the continuous occurrence of epileptiform activity.}, Author = {Cossart, R. and Dinocourt, C. and Hirsch, J. C. and Merchan-Perez, A. and De Felipe, J. and Ben-Ari, Y. and Esclapez, M. and Bernard, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {gamma-Aminobutyric Acid;Research Support, Non-U.S. Gov't;Excitatory Amino Acid Antagonists;Animals;In Vitro;Rats;Muscarinic Agonists;21 Epilepsy;Patch-Clamp Techniques;Hippocampus;Pyramidal Cells;Kainic Acid;Calcium-Binding Protein, Vitamin D-Dependent;RNA, Messenger;Dendrites;Action Potentials;Somatostatin;Glutamate Decarboxylase;21 Neurophysiology;Neurons;Epilepsy, Temporal Lobe;Interneurons;24 Pubmed search results 2008;Isoenzymes;Neural Inhibition;Excitatory Postsynaptic Potentials}, Medline = {20577665}, Month = {1}, Nlm_Id = {9809671}, Number = {1}, Organization = {INMED, INSERM Unit{\'e} 29, Avenue de Luminy, B.P. 13, 13 273 Marseille Cedex 09, France.}, Pages = {52-62}, Pubmed = {11135645}, Title = {Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy}, Uuid = {3FFE9306-DC5B-43FC-BCF9-9557B07A28E4}, Volume = {4}, Year = {2001}, url = {papers/Cossart_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/82900}} @article{Cossart:2003, Abstract = {The cerebral cortex receives input from lower brain regions, and its function is traditionally considered to be processing that input through successive stages to reach an appropriate output. However, the cortical circuit contains many interconnections, including those feeding back from higher centres, and is continuously active even in the absence of sensory inputs. Such spontaneous firing has a structure that reflects the coordinated activity of specific groups of neurons. Moreover, the membrane potential of cortical neurons fluctuates spontaneously between a resting (DOWN) and a depolarized (UP) state, which may also be coordinated. The elevated firing rate in the UP state follows sensory stimulation and provides a substrate for persistent activity, a network state that might mediate working memory. Using two-photon calcium imaging, we reconstructed the dynamics of spontaneous activity of up to 1,400 neurons in slices of mouse visual cortex. Here we report the occurrence of synchronized UP state transitions ('cortical flashes') that occur in spatially organized ensembles involving small numbers of neurons. Because of their stereotyped spatiotemporal dynamics, we conclude that network UP states are circuit attractors--emergent features of feedback neural networks that could implement memory states or solutions to computational problems.}, Author = {Cossart, Rosa and Aronov, Dmitriy and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Electrophysiology;Calcium Signaling;In Vitro;Animals;Memory;Neocortex;Monte Carlo Method;Kinetics;Mice, Inbred C57BL;21 Calcium imaging;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Neurons;Membrane Potentials;Photons;Mice;21 Cortical oscillations;24 Pubmed search results 2008;Visual Cortex;Research Support, Non-U.S. Gov't}, Medline = {22633897}, Month = {5}, Nlm_Id = {0410462}, Number = {6937}, Organization = {Department of Biological Sciences, Columbia University, New York, New York 10027, USA. rcossart\@biology.columbia.edu}, Pages = {283-8}, Pii = {nature01614}, Pubmed = {12748641}, Title = {Attractor dynamics of network UP states in the neocortex}, Uuid = {38D2900D-8F6D-492C-823D-EEA24F5F3BD5}, Volume = {423}, Year = {2003}, url = {papers/Cossart_Nature2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01614}} @article{Cossart:2001a, Abstract = {We report that kainate receptors are present on presynaptic GABAergic terminals contacting interneurons and that their activation increases GABA release. Application of kainate increased the frequency of miniature inhibitory postsynaptic currents recorded in CA1 interneurons. Local applications of glutamate but not of AMPA or NMDA also increased GABA quantal release. Application of kainate as well as synaptically released glutamate reduced the number of failures of GABAergic neurotransmission between interneurons. Thus, activation of presynaptic kainate receptors increases the probability of GABA release at interneuron-interneuron synapses. Glutamate may selectively control the communication between interneurons by increasing their mutual inhibition.}, Author = {Cossart, R. and Tyzio, R. and Dinocourt, C. and Esclapez, M. and Hirsch, J. C. and Ben-Ari, Y. and Bernard, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Research Support, Non-U.S. Gov't;Receptors, Presynaptic;21 Neurophysiology;Excitatory Amino Acid Agonists;Rats;Pyramidal Cells;Hippocampus;Signal Transduction;Rats, Wistar;Receptors, Kainic Acid;Kainic Acid;Interneurons;gamma-Aminobutyric Acid;Animals;Glutamic Acid;24 Pubmed search results 2008;21 Epilepsy}, Medline = {21134730}, Month = {2}, Nlm_Id = {8809320}, Number = {2}, Organization = {INMED, INSERM U29, Parc scientifique de Luminy, B.P. 13, 13273, Marseille, France}, Pages = {497-508}, Pii = {S0896-6273(01)00221-5}, Pubmed = {11239438}, Title = {Presynaptic kainate receptors that enhance the release of GABA on CA1 hippocampal interneurons}, Uuid = {72ABE966-222D-4224-9E90-ECC749B058CD}, Volume = {29}, Year = {2001}} @article{Cossart:2002, Abstract = {The relative contribution of kainate receptors to ongoing glutamatergic activity is at present unknown. We report the presence of spontaneous, miniature, and minimal stimulation-evoked excitatory postsynaptic currents (EPSCs) that are mediated solely by kainate receptors (EPSC(kainate)) or by both AMPA and kainate receptors (EPSC(AMPA/kainate)). EPSC(kainate) and EPSC(AMPA/kainate) are selectively enriched in CA1 interneurons and mossy fibers synapses of CA3 pyramidal neurons, respectively. In CA1 interneurons, the decay time constant of EPSC(kainate) (circa 10 ms) is comparable to values obtained in heterologous expression systems. In both hippocampal neurons, the quantal release of glutamate generates kainate receptor-mediated EPSCs that provide as much as half of the total glutamatergic current. Kainate receptors are, therefore, key players of the ongoing glutamatergic transmission in the hippocampus.}, Author = {Cossart, Rosa and Epsztein, J{\'e}r\^{o}me and Tyzio, Roman and Becq, H{\'e}l\`{e}ne and Hirsch, June and Ben-Ari, Yehezkel and Cr{\'e}pel, Val{\'e}rie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Excitatory Postsynaptic Potentials;Excitatory Amino Acid Antagonists;Electric Stimulation;Presynaptic Terminals;Animals;Rats;Glutamic Acid;Synaptic Transmission;21 Epilepsy;Synaptic Vesicles;Kinetics;Hippocampus;Pyramidal Cells;Rats, Wistar;Receptors, AMPA;Organ Culture Techniques;Male;Mossy Fibers, Hippocampal;21 Neurophysiology;Receptors, Kainic Acid;Sodium Channel Blockers;GABA Antagonists;Interneurons;24 Pubmed search results 2008;Dynorphins;Research Support, Non-U.S. Gov't}, Medline = {22120386}, Month = {7}, Nlm_Id = {8809320}, Number = {1}, Organization = {INMED-INSERM U.29 and Universit{\'e} de La M{\'e}diterran{\'e}e, Parc scientifique de Luminy, BP 13, 13273 Marseille Cedex 9, France.}, Pages = {147-59}, Pii = {S0896627302007535}, Pubmed = {12123615}, Title = {Quantal release of glutamate generates pure kainate and mixed AMPA/kainate EPSCs in hippocampal neurons}, Uuid = {0ED55826-4824-4E04-BD4A-DB06DA25C42C}, Volume = {35}, Year = {2002}} @article{Cossart:2005a, Abstract = {Because blocking GABAergic neurotransmission in control tissue generates seizures and because GABA boosters control epilepsy in many patients, studies on epilepsies have been dominated by the axiom that seizures are generated by a failure of GABA-mediated inhibition. However, GABAergic interneurons and synapses are heterogeneous and have many roles that go beyond the straightforward concept of "inhibition of the target". Operation of such a diversified system cannot be ascribed to a single mechanism. In epileptic tissue, GABAergic networks undergo complex rewiring at the anatomical, physiological and functional levels; GABAergic synapses are still operative but show unique features, including excitatory effects. Therefore, inhibition is not a uniform notion and the concept of "failure" of inhibition in epilepsies must be reassessed. Seizures are not generated in a normal circuit in which GABA-mediated inhibition is simply impaired, but in a profoundly rewired network in which several properties of GABA function are altered. This review is part of the TINS Interneuron Diversity series.}, Author = {Cossart, Rosa and Bernard, Christophe and Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Epilepsy;Synapses;Somatostatin;21 Epilepsy;21 Neurophysiology;Models, Neurological;Signal Transduction;gamma-Aminobutyric Acid;Interneurons;Humans;Animals;24 Pubmed search results 2008;Neurons;review}, Month = {2}, Nlm_Id = {7808616}, Number = {2}, Organization = {INMED-INSERM, 163 Route de Luminy, 13273 Marseille Cedex 09, Marseille, France.}, Pages = {108-15}, Pii = {S0166-2236(04)00367-4}, Pubmed = {15667934}, Title = {Multiple facets of GABAergic neurons and synapses: multiple fates of GABA signalling in epilepsies}, Uuid = {EF0BDA8C-22B4-46FD-A141-F12DEEC15DC0}, Volume = {28}, Year = {2005}, url = {papers/Cossart_TrendsNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2004.11.011}} @article{Cotrina:1998, Abstract = {Gap junctions are highly conductive channels that allow the direct transfer of intracellular messengers such as Ca2+ and inositol triphosphate (IP3) between interconnected cells. In brain, astrocytes are coupled extensively by gap junctions. We found here that gap junctions among astrocytes in acutely prepared brain slices as well as in culture remained open during ischemic conditions. Uncoupling first occurred after the terminal loss of plasma membrane integrity. Gap junctions therefore may link ischemic astrocytes in an evolving infarct with the surroundings. The free exchange of intracellular messengers between dying and potentially viable astrocytes might contribute to secondary expansion of ischemic lesions. 0270-6474 Journal Article}, Author = {Cotrina, M. L. and Kang, J. and Lin, J. H. and Bueno, E. and Hansen, T. W. and He, L. and Liu, Y. and Nedergaard, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci}, Keywords = {Hydrogen-Ion Concentration;Organ Culture;06 Adult neurogenesis injury induced;Male;Astrocytes/cytology/*physiology;Cerebral Cortex/blood supply/cytology;Animals;Cells, Cultured;D abstr;Protons;Ionophores/pharmacology;Thapsigargin/pharmacology;Gap Junctions/drug effects/immunology/*metabolism;Hippocampus/blood supply/cytology;Support, U.S. Gov't, P.H.S.;Rats, Sprague-Dawley;Cell Membrane/metabolism;Isoquinolines/pharmacokinetics;Fluorescent Dyes/pharmacokinetics;Enzyme Inhibitors/pharmacology;Rats;Female;Cell Survival/physiology;Brain Ischemia/*metabolism;Support, Non-U.S. Gov't;Second Messenger Systems/physiology;Apoptosis/physiology;Phosphorylation;Cerebral Infarction/metabolism;Calcium/metabolism/pharmacology}, Number = {7}, Organization = {Department of Cell Biology, New York Medical College, Valhalla, New York 10595, USA.}, Pages = {2520-37}, Pubmed = {9502812}, Title = {Astrocytic gap junctions remain open during ischemic conditions}, Uuid = {7BB9BEE6-3DB4-46FA-AD84-221329D9ED1D}, Volume = {18}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9502812}} @article{Couillard-Despres:2005, Abstract = {Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain. Doublecortin (DCX) has recently been used as a marker for neurogenesis. However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors. Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis. Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth. Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation. We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis. Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions.}, Author = {Couillard-Despres, Sebastien and Winner, Beate and Schaubeck, Susanne and Aigner, Robert and Vroemen, Maurice and Weidner, Norbert and Bogdahn, Ulrich and Winkler, J{\"u}rgen and Kuhn, Hans-Georg G. and Aigner, Ludwig}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {01 Adult neurogenesis general;02 Adult neurogenesis migration}, Month = {1}, Nlm_Id = {8918110}, Number = {1}, Organization = {Volkswagen-Foundation Junior Group, University of Regensburg, Franz-Josef-Strauss Allee 11, 93053 Regensburg, Germany.}, Pages = {1-14}, Pii = {EJN3813}, Pubmed = {15654838}, Title = {Doublecortin expression levels in adult brain reflect neurogenesis}, Uuid = {AE708C23-95D4-44C3-924F-2A8E153194EA}, Volume = {21}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2004.03813.x}} @article{Coull:1999, Abstract = {Noradrenaline is implicated in the modulation of attention and arousal, but the neuroanatomical basis of this effect in humans is unknown. A previous functional neuroimaging study failed to find clear effects of clonidine (alpha2 adrenoceptor agonist) on activity of brain regions implicated in attention. Therefore, we now investigate whether clonidine affects the functional integration of a neuroanatomical attentional network, by modulating connectivity between brain regions rather than activity within discrete regions. Following infusion of either clonidine or placebo, positron emission tomography measurements of brain activity were collected in 13 normal subjects while they were either resting or performing an attentional task. Effective connectivity analysis showed that during rest, clonidine decreased the functional strength of connections both from frontal cortex to thalamus and in pathways to and from visual cortex. Conversely, during the attentional task, functional integration generally increased, with changes being centered on parietal cortex (increased connectivity from locus coeruleus to parietal cortex and from parietal cortex to thalamus and frontal cortex). A drug-induced increase in the modulatory effects of frontal cortex on projections from locus coeruleus to parietal cortex was also observed. Collectively, these results highlight cognitively dissociable effects of clonidine on interactions among functionally integrated brain regions and implicate the noradrenergic system in mediating the functional integration of attentional brain systems. The context-sensitive nature of the changes are consistent with observations that noradrenergic drugs have differential effects on brain processes depending on subjects' underlying arousal levels. More generally, the results illustrate the dynamic plasticity of cognitive brain systems following neurochemical challenge.}, Author = {Coull, J. T. and B{\"u}chel, C. and Friston, K. J. and Frith, C. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1053-8119}, Journal = {Neuroimage}, Keywords = {Nerve Net;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Adolescent;Adult;Neuronal Plasticity;Neural Pathways;Attention;Norepinephrine;Behavior;Locus Coeruleus;Humans;Male;Thalamus;Neurons;Frontal Lobe}, Medline = {20070571}, Month = {12}, Nlm_Id = {9215515}, Number = {6}, Organization = {Wellcome Department of Cognitive Neurology, Institute of Neurology, 12 Queen Square, London, WC1N 3BG, United Kingdom. j.coull\@fil.ion.ucl.ac.uk}, Pages = {705-15}, Pii = {S105381199990513X}, Pubmed = {10600416}, Title = {Noradrenergically mediated plasticity in a human attentional neuronal network}, Uuid = {3FD2B8CF-A550-4B6F-9289-31188CA96411}, Volume = {10}, Year = {1999}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/nimg.1999.0513}} @article{Coulter:2000, Abstract = {Temporal lobe epilepsy is associated with circuit rearrangements within the hippocampus. Mossy fibers sprout and pathologically innervate the inner molecular layer of the dentate gyrus, providing a recurrent excitatory pathway not present in the control brain. In addition to releasing glutamate, these recurrent collaterals also release zinc, which can accumulate in high concentrations in the extracellular space. Accompanying these dentate gyrus circuit rearrangements are alterations in the subunit expression patterns and pharmacology of gamma-aminobutyric acid A (GABAA) receptors in dentate granule cells. In normal, control granule cells, GABAA receptors are zinc insensitive as a result of high levels of expression of the alpha1 subunit in these cells. In epileptic brain, expression of alpha1 subunits decreases and expression of alpha4 and delta subunits increases, leading to the assembly of GABAA receptors that are exquisitely zinc sensitive. This temporal and spatial association of the expression of zinc-sensitive GABAA receptors and the emergence of a zinc-delivery system unique to the epileptic hippocampus has led to the formulation of an hypothesis that suggests that zinc release during repetitive activation of the dentate gyrus may lead to a catastrophic failure of inhibition under conditions mediating seizure initiation. This could contribute to the limbic hyperexcitability characteristic of temporal lobe epilepsy.}, Author = {Coulter, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {21 Epilepsy;24 Pubmed search results 2008;21 Neurophysiology;Mossy Fibers, Hippocampal;Epilepsy, Temporal Lobe;Zinc;Models, Neurological;Dentate Gyrus;Disease Models, Animal;Humans;Animals;review;Receptors, GABA-A}, Medline = {20452157}, Nlm_Id = {2983306R}, Organization = {Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, USA.}, Pages = {S96-9}, Pubmed = {10999528}, Title = {Mossy fiber zinc and temporal lobe epilepsy: pathological association with altered "epileptic" gamma-aminobutyric acid A receptors in dentate granule cells}, Uuid = {CCFB0B4A-E223-4605-BFD6-D6006895C4F4}, Volume = {41 Suppl 6}, Year = {2000}} @article{Coulter:2002, Author = {Coulter,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1535-7597}, Journal = {Epilepsy Curr}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {11}, Nlm_Id = {101135954}, Number = {6}, Pages = {194-195}, Pubmed = {15309116}, Title = {Sprouted Mossy Fibers Form Primarily Excitatory Connections}, Uuid = {CD086B2E-B022-4AC7-8E7C-8AA4CF0D5995}, Volume = {2}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1046/j.1535-7597.2002.00073.x}} @article{Coulter:2004, Author = {Coulter, Douglas A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1535-7597}, Journal = {Epilepsy Curr}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Nlm_Id = {101135954}, Number = {6}, Pages = {250-3}, Pubmed = {16059517}, Title = {Functional consequences of hilar mossy cell loss in temporal lobe epilepsy: proepileptic or antiepileptic?}, Uuid = {938F5A30-4CDF-491B-BFF4-D92F2D2B587E}, Volume = {4}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1535-7597.2004.46012.x}} @article{Covolan:2000, Abstract = {Dentate granule cells are generally considered to be relatively resistant to excitotoxicity and have been associated with robust synaptogenesis after neuronal damage. Synaptic reorganization of dentate granule cell axons, the mossy fibers, has been suggested to be relevant for hyperexcitability in human temporal lobe epilepsy and animal models. A recent hypothesis suggested that mossy-fiber sprouting is dependent on newly formed dentate granule cells. However, we recently demonstrated that cycloheximide (CHX) can block the mossy- fiber sprouting that would otherwise be induced by different epileptogenic agents and does not interfere with epileptogenesis in those models. Here, we investigated cell damage and neurogenesis in the dentate gyrus of pilocarpine- or kainate-treated animals with or without coadministration of CHX. Dentate granule cells were highly vulnerable to pilocarpine induced-status epilepticus (SE), but were hardly damaged by kainate-induced SE. CHX pretreatment markedly reduced the number of injured neurons after pilocarpine-induced SE. Induction of SE dramatically increased the mitotic rate of KA- and KA + CHX- treated animals. Induction of SE in animals injected with pilocarpine alone led to 2-7-fold increases in the mitotic rate of dentate granule cells as compared to 5- and 30-fold increases for pilocarpine + CHX animals. We suggest that such increased mitotic rates might be associated with a protection of a vulnerable precursor cell population that would otherwise degenerate after pilocarpine-induced SE. We further suggest that mossy-fiber sprouting and neurogenesis of granule cells are not necessarily linked to one another. Using Smart Source Parsing}, Author = {Covolan, L. and Ribeiro, L. T. and Longo, B. M. and Mello, L. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Hippocampus}, Keywords = {Status Epilepticus/chemically induced/*pathology;Pilocarpine;Rats;Muscarinic Agonists;Cycloheximide/pharmacology;Excitatory Amino Acid Agonists;Mossy Fibers, Hippocampal/chemistry/*pathology;Animal;Bromodeoxyuridine/analysis;Rats, Wistar;Kainic Acid;Male;Staining and Labeling;Support, Non-U.S. Gov't;06 Adult neurogenesis injury induced;Protein Synthesis Inhibitors/pharmacology;Antimetabolites/analysis;D-9;Mitosis/drug effects}, Number = {2}, Organization = {Department of Physiology, Universidade Federal de Sao Paulo, Brazil.}, Pages = {169-80}, Title = {Cell damage and neurogenesis in the dentate granule cell layer of adult rats after pilocarpine- or kainate-induced status epilepticus}, Uuid = {2E76A045-F6E3-49F6-9E77-8184FF3E9F40}, Volume = {10}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10791839}} @article{Cowan:1994, Abstract = {1. Spontaneous fluctuations of membrane potential, patterns of spontaneous firing, dendritic branching patterns, and intracortical and striatal axonal arborizations were compared for two types of corticostriatal neurons in the medial agranular cortex of urethan-anesthetized rats: 1) pyramidal tract (PT) cells identified by antidromic activation from the medullary pyramid and 2) crossed corticostriatal (CST) neurons identified by antidromic activation from the contralateral neostriatum. The ipsilateral corticostriatal projections of intracellularly stained PT neurons as well as contralateral corticostriatal neurons were confirmed after labeling by intracellular injection of biocytin. 2. All well-stained PT neurons had intracortical and intrastriatal collaterals. The more common type (6 of 8) was a large, deep layer V neuron that had an extensive intracortical axon arborization but a limited axon arborization in the neostriatum. The less common type of PT neuron (2 of 8) was a medium-sized, superficial layer V neuron that had a limited intracortical axon arborization but a larger and more dense intrastriatal axonal arborization. Both subclasses of PT neurons had anatomic and physiological properties associated with slow PT cells in cats and monkeys and conduction velocities < 10 m/s. All of the PT cells but one were regular spiking cells. The exception cell fired intrinsic bursts. 3. Intracellularly stained CST neurons were located in the superficial half of layer V and the deep part of layer III. Their layer I apical dendrites were few and sparsely branched. Their axons gave rise to an extensive arbor of local axon collaterals that distributed in the region of the parent neuron, frequently extending throughout the more superficial layers, including layer I. Axon collaterals were also traced to the corpus callosum, as expected from their contralateral projections, and they contributed axon collaterals to the ipsilateral neostriatum. In the neostriatum, these axons formed extended arborizations sparsely occupying a large volume of striatal tissue. All CST neurons were regular spiking cells. 4. Both types of cells displayed spontaneous membrane fluctuations consisting of a polarized state (-60 to -90 mV) that was interrupted by 0.1- to 3.0-s periods of depolarization (-55 to -45 mV) accompanied by action potentials. The membrane potential was relatively constant in each state, and transitions between the depolarized and hyperpolarized states were sometimes periodic with a frequency of 0.3-1.5 Hz. A much faster (30-45 Hz) subthreshold oscillation of the membrane potential was observed only in the depolarized state and triggered action potentials that locked to the depolarizing peaks of this rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Cowan, R. L. and Wilson, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Electric Stimulation;Lysine;Electrophysiology;Animals;Rats;Neural Pathways;research support, u.s. gov't, p.h.s. ;Axons;Rats, Sprague-Dawley;Pyramidal Cells;Male;Dendrites;Action Potentials;Histocytochemistry;Cerebral Cortex;21 Neurophysiology;21 Circuit structure-function;Neostriatum;Neurons;Membrane Potentials;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, University of Tennessee, Memphis 38163.}, Pages = {17-32}, Pubmed = {8158226}, Title = {Spontaneous firing patterns and axonal projections of single corticostriatal neurons in the rat medial agranular cortex}, Uuid = {79528774-AC06-4F43-B557-E9F0221F4EA8}, Volume = {71}, Year = {1994}} @article{Cowan:2001, Abstract = {Caspase-9, an initiator caspase, and caspase-3, an effector caspase, have been suggested to mediate the terminal stages of neuronal apoptosis, but little is known about their activation in vivo. We examined temporal and spatial aspects of caspase-9 and -3 activation in olfactory receptor neurons (ORNs) undergoing apoptosis after target removal in vivo. After removal of the olfactory bulb, enhanced expression of procaspase-9 and -3 is observed in ORNs, followed by activation initially at the level of the lesion, then in axons, and only later in the ORN soma. We established the amyloid precursor-like protein-2 (APLP2) as a caspase substrate that is cleaved in an identical spatiotemporal pattern, suggesting its cleavage is the result of retrograde propagation of a pro-apoptotic signal in a caudorostral wave from the synapse through the axon to the ORN cell body. A null mutation in caspase-3 causes a change in axonal patterning indicative of an overall developmental expansion of the ORN population, and mature ORNs of caspase-3 knock-outs do not undergo caspase-dependent terminal dUTP nick end labeling-positive apoptosis after olfactory bulb removal. These results demonstrate that ORNs require caspase-3 activation to undergo normal developmental and mature target-deprived apoptosis. In addition, we demonstrate an axonal site of action for caspase-3 and -9 and show that regulation and activation of caspase-3 and -9 leading to apoptosis is a highly ordered process that occurs initially at the presynaptic level and only later at the cell body after deafferentation.}, Author = {Cowan, C. M. and Thai, J. and Krajewski, S. and Reed, J. C. and Nicholson, D. W. and Kaufmann, S. H. and Roskams, A. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:44 -0400}, Journal = {J Neurosci}, Keywords = {I pdf;13 Olfactory bulb anatomy}, Number = {18}, Organization = {Centre for Molecular Medicine and Therapeutics, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.}, Pages = {7099-109.}, Title = {Caspases 3 and 9 send a pro-apoptotic signal from synapse to cell body in olfactory receptor neurons}, Uuid = {6B9B5E48-2D76-4E7D-B9D1-089855113E38}, Volume = {21}, Year = {2001}, url = {papers/Cowan_JNeurosci2001.pdf}} @article{Cowan:2005, Abstract = {We have explored the use of embryonic stem cells as an alternative to oocytes for reprogramming human somatic nuclei. Human embryonic stem (hES) cells were fused with human fibroblasts, resulting in hybrid cells that maintain a stable tetraploid DNA content and have morphology, growth rate, and antigen expression patterns characteristic of hES cells. Differentiation of hybrid cells in vitro and in vivo yielded cell types from each embryonic germ layer. Analysis of genome-wide transcriptional activity, reporter gene activation, allele-specific gene expression, and DNA methylation showed that the somatic genome was reprogrammed to an embryonic state. These results establish that hES cells can reprogram the transcriptional state of somatic nuclei and provide a system for investigating the underlying mechanisms.}, Author = {Cowan, Chad A. and Atienza, Jocelyn and Melton, Douglas A. and Eggan, Kevin}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Cell Differentiation;22 Stem cells;Cell Line;24 Pubmed search results 2008;Mice, Nude;Male;Animals;Pluripotent Stem Cells;Transcription, Genetic;Gene Expression Regulation, Developmental;Phenotype;Polyploidy;Transfection;Cell Transplantation;Chromosomes, Human;Hybrid Cells;Cell Cycle;08 Aberrant cell cycle;Biological Markers;Gene Expression Profiling;Epigenesis, Genetic;Teratoma;Embryo;Female;Cell Nucleus;Fibroblasts;Adult;Mice;Research Support, Non-U.S. Gov't;Cell Fusion;Humans;Cell Shape}, Month = {8}, Nlm_Id = {0404511}, Number = {5739}, Organization = {Howard Hughes Medical Institute, Harvard Stem Cell Institute, Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA.}, Pages = {1369-73}, Pii = {309/5739/1369}, Pubmed = {16123299}, Title = {Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells}, Uuid = {FF6AA2E1-D3AD-41BE-94CA-9C48153A5D54}, Volume = {309}, Year = {2005}, url = {papers/Cowan_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1116447}} @article{Craig:1996, Abstract = {The lateral ventricle subependyma in the adult mammalian forebrain contains both neural stem and progenitor cells. This study describes the in situ modulation of these subependymal neural precursor populations after intraventricular administration of exogenous growth factors. In vivo infusion of epidermal growth factor (EGF) into adult mouse forebrain for 6 consecutive days resulted in a dramatic increase in the proliferation and total number of subependymal cells and induced their migration away from the lateral ventricle walls into adjacent parenchyma. Immediately after EGF infusion, immunohistochemical characterization of the EGF-expanded cell population demonstrated that >95\%of these cells were EGF receptor- and nestin-positive, whereas only 0.9\%and 0.2\%labeled for astrocytic and neuronal markers, respectively. Seven weeks after EGF withdrawal, 25\%of the cells induced to proliferate after 6d of EGF were still detectable; 28\%of these cells had differentiated into new astrocytes and 3\%into new neurons in the cortex, striatum, and septum. Newly generated oligodendrocytes were also observed. These in vivo results (1) confirm the existence of EGF-responsive subependymal neural precursor cells in the adult mouse forebrain and (2) suggest that EGF acts directly as a proliferation, survival, and migration factor for subependymal precursor cells to expand these populations and promote the movement of these cells into normal brain parenchyma. Thus, in situ modulation of endogenous forebrain precursor cells represents a novel model for studying neural development in the adult mammalian brain and may provide insights that will achieve adult replacement of neurons and glia lost to disease or trauma.}, Author = {Craig, C. G. and Tropepe, V. and Morshead, C. M. and Reynolds, B. A. and Weiss, S. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci}, Keywords = {Ependyma/*drug effects;Time Factors;Dose-Response Relationship, Drug;Brain/*drug effects;Animal;Astrocytes/metabolism;Epidermal Growth Factor/*pharmacology;04 Adult neurogenesis factors;Neurons/metabolism;Support, Non-U.S. Gov't;C-5;Mice;Cell Count/drug effects;Mice, Inbred Strains}, Number = {8}, Organization = {Deparment of Anatomy and Cell Biology, University of Toronto, Ontario, Canada.}, Pages = {2649-58.}, Title = {In vivo growth factor expansion of endogenous subependymal neural precursor cell populations in the adult mouse brain}, Uuid = {1D9DB226-AA0D-453C-9BD6-EF04A1C6B966}, Volume = {16}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8786441}} @article{Craig:1999, Abstract = {Initial experiments to evaluate the in vivo fate(s) of constitutively proliferating subependymal cells determined that, following in vivo labeling of this population by infection with a retrovirus containing a beta-galactosidase reporter gene, there was a progressive and eventually complete loss of histochemically beta-galactosidase-positive cells within the lateral ventricle subependyma with increasing survival times of up to 28 days after retroviral infection. Subsequent experiments were designed to ascertain the potential contributions of: (i) the migration of subependymal cells away from the forebrain lateral ventricles; and (ii) the down-regulation of the retroviral reporter gene expression. Retroviral lineage tracing experiments demonstrate that a major in vivo fate for constitutively proliferating subependymal cells is their rostral migration away from the walls of the lateral ventricle to the olfactory bulb. Although down-regulation of retroviral reporter gene expression does not contribute to the loss of detection of beta-galactosidase-labeled cells from the lateral ventricle subependyma, it does result in an underestimation of the absolute number of retrovirally labeled cells in the olfactory bulb at longer survival times. Furthermore, a temporal decrease in the double labeling of beta-galactosidase-labeled cells with [3H]thymidine was observed, indicating that only a subpopulation of the migratory subependymal- derived cells continue to actively proliferate en route to the olfactory bulb. These two events may contribute to the lack of a significant increase in the total number of retrovirally labeled subependymal cells during rostral migration. Evidence from separately published studies suggests that cell death is also an important regulator of the size of the constitutively proliferating subependymal population. In summary, in vivo studies utilizing retroviral reporter gene labeling demonstrate that constitutively proliferating subependymal cells born in the lateral ventricle migrate rostrally to the olfactory bulb. Loss of proliferation potential and retroviral reporter gene down-regulation contribute to the lack of any significant increase in the total number of labeled cells recovered in the olfactory bulb. Using Smart Source Parsing}, Author = {Craig, C. G. and D'sa, R. and Morshead, C. M. and Roach, A. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Neuroscience}, Keywords = {Prosencephalon/*cytology;Genetic Vectors/analysis/genetics;Animal;Stem Cells/cytology;02 Adult neurogenesis migration;Cell Movement;Ependyma/*cytology;beta-Galactosidase/genetics;DNA Replication;Male;Support, Non-U.S. Gov't;Retroviridae/genetics;B;Cell Lineage;Olfactory Bulb/cytology;Mice;Cell Division;Genes, Reporter;Gene Expression;Cerebral Ventricles/cytology}, Number = {3}, Organization = {Department of Anatomy and Cell Biology, University of Toronto, Ontario, Canada.}, Pages = {1197-206}, Title = {Migrational analysis of the constitutively proliferating subependyma population in adult mouse forebrain}, Uuid = {3F782E5C-A0C0-4A00-BE5E-778280DFE379}, Volume = {93}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10473285}} @article{Crair:1999, Abstract = {Experimental studies over the past year have shown that neural activity has a range of effects on the development of neural pathways. Although activity appears unimportant for establishing many aspects of the gross morphology and topology of the brain, there are many cases where the presence of neural activity is essential for the formation of a mature system of neural connections; in some instances, the pattern of neural activity actually orchestrates the final arrangement of neural connections.}, Author = {Crair, M. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Receptors, N-Methyl-D-Aspartate;Eye;Superior Colliculi;Mice, Knockout;24 Pubmed search results 2008;Cats;Neuronal Plasticity;Neural Pathways;Embryonic Induction;Ferrets;Amphibia;Animals;Brain;review;Mice; 21 Activity-development; currOpinRvw}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Division of Neuroscience Program in Developmental Biology Room S-603 Baylor College of Medicine One Baylor Plaza Houston Texas 77030 USA. mikec\@sensor.bcm.tmc.edu}, Pages = {88-93}, Pii = {S0959-4388(99)80011-7}, Pubmed = {10072369}, Title = {Neuronal activity during development: permissive or instructive?}, Uuid = {08791AE4-66B5-400B-A375-A0D7DBE64F45}, Volume = {9}, Year = {1999}, url = {papers/Crair_CurrOpinNeurobiol1999.pdf}} @article{Crair:2001, Abstract = {Previous anatomic studies of the geniculocortical projection showed that ocular dominance columns emerge by 3 weeks of age in cat visual cortex, but recent optical imaging experiments have revealed a pattern of physiologic eye dominance by the end of the second week of life. We used two methods to search for an anatomic correlate of this early functional ocular dominance pattern. First, retrograde labeling of lateral geniculate nucleus (LGN) inputs to areas of cortex preferentially activated by one eye showed that the geniculocortical projection was already partially segregated by eye at postnatal day 14 (P14). Second, transneuronal label of geniculocortical afferents in flattened sections of cortex after a tracer injection into one eye showed a periodic pattern at P14 but not at P7. In the classic model for the development of ocular dominance columns, initially overlapping geniculocortical afferents segregate by means of an activity-dependent competitive process. Our data are consistent with this model but suggest that ocular dominance column formation begins between P7 and P14, approximately a week earlier than previously believed. The functional and anatomic data also reveal an early developmental bias toward contralateral eye afferents. This initial developmental bias is not consistent with a strictly Hebbian model for geniculocortical afferent segregation. The emergence of ocular dominance columns before the onset of the critical period for visual deprivation also suggests that the mechanisms for ocular dominance column formation may be partially distinct from those mediating plasticity later in life.}, Author = {Crair, M. C. and Horton, J. C. and Antonini, A. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 20:17:35 +0000}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Aging;Visual Cortex;research support, non-u.s. gov't;Cats;Functional Laterality;Geniculate Bodies;Animals, Newborn;Ocular Physiology;research support, u.s. gov't, p.h.s.;Animals;Synaptic Transmission;24 Pubmed search results 2008;Neurons; 21 Activity-development; currOpinRvw}, Month = {2}, Nlm_Id = {0406041}, Number = {2}, Organization = {W.M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, California 94143-0444, USA.}, Pages = {235-49}, Pii = {10.1002/1096-9861(20010205)430:2<235::AID-CNE1028>3.0.CO;2-P}, Pubmed = {11135259}, Title = {Emergence of ocular dominance columns in cat visual cortex by 2 weeks of age}, Uuid = {3FA6C0D1-139A-49B2-A4E6-AAAE4240C5E3}, Volume = {430}, Year = {2001}, url = {papers/Crair_JCompNeurol2001.pdf}} @article{Crair:1997, Abstract = {In the primary visual cortex of monkey and cat, ocular dominance and orientation are represented continuously and simultaneously, so that most neighboring neurons respond optimally to visual stimulation of the same eye and orientation. Maps of stimulus orientation are punctuated by singularities referred to as "pinwheel centers," around which all orientations are represented. Given that the orientation map is mostly continuous, orientation singularities are a mathematical necessity unless the map consists of perfectly parallel rows, and there is no evidence that the singularities play a role in normal function or development. We report here that in cats there is a strong tendency for peaks of ocular dominance to lie on the pinwheel center singularities of the orientation map. This relationship predicts but is not predicted by the tendencies, previously reported, for pinwheels to lie near the center lines of ocular dominance bands and for iso-orientation bands to cross ocular dominance boundaries at right angles. The coincidence of ocular dominance peaks with orientation singularities is likely to reflect a strong underlying functional link between the two visual cortical maps.}, Author = {Crair, M. C. and Ruthazer, E. S. and Gillespie, D. C. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-27 11:35:53 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Visual Cortex;Pattern Recognition, Visual;Image Processing, Computer-Assisted;Orientation;Cats;Brain Mapping;Motion Perception;research support, u.s. gov't, p.h.s.;Animals;Synaptic Transmission;24 Pubmed search results 2008;Dominance, Cerebral; 21 Activity-development}, Month = {6}, Nlm_Id = {0375404}, Number = {6}, Organization = {Department of Physiology, W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco 94143-0444, USA.}, Pages = {3381-5}, Pubmed = {9212282}, Title = {Ocular dominance peaks at pinwheel center singularities of the orientation map in cat visual cortex}, Uuid = {3C1CD2D6-0E92-494F-A016-4E36374E4599}, Volume = {77}, Year = {1997}, url = {papers/Crair_JNeurophysiol1997.pdf}} @article{Crair:1995, Abstract = {In mammalian development, the refinement of topographical projections from the thalamus to the cortex is thought to arise through an activity-dependent process in which thalamic axons compete for cortical targets. In support of this view, if activity is altered during a critical period in early development, normal connectivity is disrupted. It has been proposed that synaptic connections are strengthened during development by correlated pre- and postsynaptic activity, and a likely mechanism for this process would be N-methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP). However, the evidence that LTP is involved in normal development remains inconclusive. We have examined LTP in the thalamocortical synapses that form whisker barrels in rat somatosensory cortex (S1). We report here that the period during which LTP can be induced matches closely the critical period during which the barrels can be modified by sensory perturbations. Moreover, the loss of susceptibility to LTP with age is accompanied by a decrease in NMDA receptor-mediated synaptic currents. These findings provide compelling evidence that LTP is important for the development of cortical circuitry.}, Author = {Crair, M. C. and Malenka, R. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Synapses;24 Pubmed search results 2008;research support, non-u.s. gov't;Rats, Sprague-Dawley;Long-Term Potentiation;Female;Rats;in vitro;Pregnancy;research support, u.s. gov't, p.h.s.;Animals;Neurons, Afferent;Receptors, N-Methyl-D-Aspartate;Somatosensory Cortex;Thalamus; 21 Activity-development}, Month = {5}, Nlm_Id = {0410462}, Number = {6529}, Organization = {Department of Psychiatry, University of California, San Francisco 94143, USA.}, Pages = {325-8}, Pubmed = {7753197}, Title = {A critical period for long-term potentiation at thalamocortical synapses}, Uuid = {BC1AA26E-212E-4C4A-A391-E2A41AA8971F}, Volume = {375}, Year = {1995}, url = {papers/Crair_Nature1995.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/375325a0}} @article{Crair:1997a, Abstract = {The significance of functional maps for cortical plasticity was investigated by imaging of intrinsic optical signals together with single-unit recording in kittens. After even a brief period of monocular deprivation during the height of the critical period, only isolated patches of visual cortex continued to respond strongly to the closed eye. These deprived-eye patches were located on the pinwheel center singularities of the orientation map and consisted of neurons that were poorly selective for stimulus orientation. Neurons in regions surrounding the deprived-eye patches responded only weakly to the deprived eye but were well tuned for the same stimulus orientation that optimally excited them when presented to the open, nondeprived eye. The coincidence of deprived-eye patches with pinwheel center singularities, and the selective loss of orientation tuning within the deprived-eye patches, indicate that the orientation and ocular dominance maps are functionally linked and provide compelling evidence that pinwheel center singularities are important for cortical plasticity.}, Author = {Crair, M. C. and Ruthazer, E. S. and Gillespie, D. C. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-04-05 11:56:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Visual Cortex;Photic Stimulation;Cats;Eye Movements;Brain Mapping;research support, u.s. gov't, p.h.s.;Animals;Vision, Monocular; 21 Activity-development;development;intrinsic signal;Sensory Deprivation;activity manipulation;function;topographic map}, Month = {8}, Nlm_Id = {8809320}, Number = {2}, Organization = {W. M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco 94143-0444, USA.}, Pages = {307-18}, Pii = {S0896-6273(00)80941-1}, Pubmed = {9292721}, Title = {Relationship between the ocular dominance and orientation maps in visual cortex of monocularly deprived cats}, Uuid = {F3E6746D-EE0B-4E5A-8633-32FDBBB0EA25}, Volume = {19}, Year = {1997}, url = {papers/Crair_Neuron1997.pdf}} @article{Crair:1998, Abstract = {The role of experience in the development of the cerebral cortex has long been controversial. Patterned visual experience in the cat begins when the eyes open about a week after birth. Cortical maps for orientation and ocular dominance in the primary visual cortex of cats were found to be present by 2 weeks. Early pattern vision appeared unimportant because these cortical maps developed identically until nearly 3 weeks of age, whether or not the eyes were open. The na{\"\i}ve maps were powerfully dominated by the contralateral eye, and experience was needed for responses to the other eye to become strong, a process unlikely to be strictly Hebbian. With continued visual deprivation, responses to both eyes deteriorated, with a time course parallel to the well-known critical period of cortical plasticity. The basic structure of cortical maps is therefore innate, but experience is essential for specific features of these maps, as well as for maintaining the responsiveness and selectivity of cortical neurons.}, Author = {Crair, M. C. and Gillespie, D. C. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Visual Cortex;Photic Stimulation;research support, non-u.s. gov't;Cats;Vision;Brain Mapping;research support, u.s. gov't, p.h.s.;Animals;Visual Pathways;24 Pubmed search results 2008;Microelectrodes;Vision, Monocular; 21 Activity-development; retinal wave paper; optical physiology; optical imaging; intrinsic signal; currOpinRvw}, Month = {1}, Nlm_Id = {0404511}, Number = {5350}, Organization = {W. M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, CA 94143, USA.}, Pages = {566-70}, Pubmed = {9438851}, Title = {The role of visual experience in the development of columns in cat visual cortex}, Uuid = {021F83BD-0445-4BE1-8BF8-CA7C89CA60B1}, Volume = {279}, Year = {1998}, url = {papers/Crair_Science1998.pdf}} @article{Cramer:2005, Abstract = {Many kinds of information are carried in the acoustic signal that reaches auditory receptor cells in the cochlea. The analysis of this information is possible in large part because of the neuronal architecture of the auditory system. The mechanisms that establish the precise circuitry that underlies auditory processing have not yet been identified. The Eph receptor tyrosine kinases and their ligands are proteins that regulate axon guidance and have been shown to contribute to the establishment of topographic projections in several areas of the nervous system. Several studies have begun to investigate whether these proteins are involved in the formation of auditory system connections. Studies of gene expression show that Eph proteins are extensively expressed in structures of the inner ear as well as in neurons in the peripheral and central components of the auditory system. Functional studies have demonstrated that Eph signaling influences the assembly of auditory pathways. These studies suggest that Eph protein signaling has a significant role in the formation of auditory circuitry.}, Author = {Cramer, Karina S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0378-5955}, Journal = {Hear Res}, Keywords = {Ephrins;Humans;24 Pubmed search results 2008;10 Development;research support, non-u.s. gov't;Mammals;10 circuit formation;Receptor, EphA1;research support, n.i.h., extramural;Birds;research support, u.s. gov't, p.h.s.;Animals;Auditory Pathways;Cochlear Nerve;review;Axons}, Month = {8}, Nlm_Id = {7900445}, Number = {1-2}, Organization = {Department of Neurobiology and Behavior, University of California, 2205 McGaugh Hall, Irvine, CA 92697-4550, USA. cramerk\@uci.edu}, Pages = {42-51}, Pii = {S0378-5955(05)00086-9}, Pubmed = {16080997}, Title = {Eph proteins and the assembly of auditory circuits}, Uuid = {A87DAD9C-54DC-47A2-B178-47D1265AAE81}, Volume = {206}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.heares.2004.11.024}} @article{Crandall:2007, Abstract = {GABA neurons of the cerebral cortex and other telencephalic structures are produced in the basal forebrain and migrate to their final destinations during the embryonic period. The embryonic basal forebrain is enriched in dopamine and its receptors, creating a favorable environment for dopamine to influence GABA neuron migration. However, whether dopamine receptor activation can influence GABA neuron migration is not known. We show that dopamine D1 receptor activation promotes and D2 receptor activation decreases GABA neuron migration from the medial and caudal ganglionic eminences to the cerebral cortex in slice preparations of embryonic mouse forebrain. Slice preparations from D1 or D2 receptor knock-out mouse embryos confirm the findings. In addition, D1 receptor electroporation into cells of the basal forebrain and pharmacological activation of the receptor promote migration of the electroporated cells to the cerebral cortex. Analysis of GABA neuron numbers in the cerebral wall of the dopamine receptor knock-out mouse embryos further confirmed the effects of dopamine receptor activation on GABA neuron migration. Finally, dopamine receptor activation mobilizes striatal neuronal cytoskeleton in a manner consistent with the effects on neuronal migration. These data show that impairing the physiological balance between D1 and D2 receptors can alter GABA neuron migration from the basal forebrain to the cerebral cortex. The intimate relationship between dopamine and GABA neuron development revealed here may offer novel insights into developmental disorders such as schizophrenia, attention deficit or autism, and fetal cocaine exposure, all of which are associated with dopamine and GABA imbalance.}, Author = {Crandall, James E. and McCarthy, Deirdre M. and Araki, Kiyomi Y. and Sims, John R. and Ren, Jia-Qian Q. and Bhide, Pradeep G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {02 Adult neurogenesis migration;10 Development;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Eunice Kennedy Shriver Center for Mental Retardation, Physiology, University of Massachusetts Medical School, Waltham, Massachusetts 02452, USA.}, Pages = {3813-22}, Pii = {27/14/3813}, Pubmed = {17409246}, Title = {Dopamine receptor activation modulates GABA neuron migration from the basal forebrain to the cerebral cortex}, Uuid = {BF35D4FF-8CC0-4C79-89F5-7B06F7BDFE33}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5124-06.2007}} @article{Cremer:1997, Abstract = {The neural cell adhesion molecule (NCAM), probably the best characterized and most abundant cell adhesion molecule on neurons, is thought to be a major regulator of axonal growth and pathfinding. Here we present a detailed analysis of these processes in mice deficient for all NCAM isoforms, generated by gene targeting. The hippocampal mossy fiber tract shows prominent expression of polysialylated NCAM and the generation of new axonal projections throughout life. Focusing on this important intrahippocampal connection, we demonstrate that in the absence of NCAM, fasciculation and pathfinding of these axons are strongly affected. In addition we show alterations in the distribution of mossy fiber terminals. The phenotype is more severe in adult than in young animals, suggesting an essential role for NCAM in the maintenance of plasticity in the mature nervous system.}, Author = {Cremer, H. and Chazal, G. and Goridis, C. and Represa, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {Aging;Staining and Labeling;Nerve Fibers;Research Support, Non-U.S. Gov't;Mice, Knockout;Golgi Apparatus;Neural Cell Adhesion Molecules;Hippocampus;Nerve Endings;Neurons;Mice, Inbred C57BL;Animals;Mice;24 Pubmed search results 2008;Mice, Inbred Strains;Axons}, Medline = {97230486}, Nlm_Id = {9100095}, Number = {5}, Organization = {IBDM, CNRS/INSERM/Universit{\'e} de la M{\'e}diterran{\'e}e, Marseille Cedex 9, France.}, Pages = {323-35}, Pii = {S1044-7431(96)90588-6}, Pubmed = {9073395}, Title = {NCAM is essential for axonal growth and fasciculation in the hippocampus}, Uuid = {03980902-0C78-46F9-96A9-D66C2B5E40A7}, Volume = {8}, Year = {1997}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/mcne.1996.0588}} @article{Cremer:1994, Abstract = {Neural-cell adhesion molecules (N-CAMs) are members of the immunoglobulin superfamily mediating homo- and heterophilic cell-cell interactions. N-CAM exists in various isoforms which are generated by alternative splicing. During embryonic development, N-CAMs are expressed in derivatives of all three germ layers, whereas in the adult animal they are predominantly present in neural tissue. Processes like neurulation, axonal outgrowth, histogenesis of the retina and development of the olfactory system are correlated with the regulated expression of N-CAMs. We show here that N-CAM-deficient mice generated by gene targeting appear healthy and fertile, but adult mutants show a 10\%reduction in overall brain weight and a 36\%decline in size of the olfactory bulb. N-CAM deficiency coincides with almost total loss of protein-bound alpha-(2,8)-linked polysialic acid, a carbohydrate structure thought to be correlated with neural development and plasticity. The animals showed deficits in spatial learning when tested in the Morris water maze, whereas activity and motor abilities appeared normal.}, Author = {Cremer, H. and Lange, R. and Christoph, A. and Plomann, M. and Vopper, G. and Roes, J. and Brown, R. and Baldwin, S. and Kraemer, P. and Scheff, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Embryo;Mutation;Base Sequence;Research Support, Non-U.S. Gov't;DNA Primers;Molecular Sequence Data;Heterozygote;Homozygote;Cell Line;Mice, Inbred C57BL;Spatial Behavior;Olfactory Bulb;Mice;Animals;24 Pubmed search results 2008;Cell Adhesion Molecules, Neuronal;Sialic Acids}, Medline = {94150622}, Month = {2}, Nlm_Id = {0410462}, Number = {6462}, Organization = {Institute for Genetics, University of Cologne, Germany.}, Pages = {455-9}, Pubmed = {8107803}, Title = {Inactivation of the N-CAM gene in mice results in size reduction of the olfactory bulb and deficits in spatial learning}, Uuid = {4189DF3B-70FF-498F-BFAB-295496647134}, Volume = {367}, Year = {1994}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/367455a0}} @article{Cremer:1998, Abstract = {Cell adhesion molecules (CAMs) are known to be involved in a variety of developmental processes that play key roles in the establishment of synaptic connectivity during embryonic development, but recent evidence implicates the same molecules in synaptic plasticity of the adult. In the present study, we have used neural CAM (NCAM)-deficient mice, which have learning and behavioral deficits, to evaluate NCAM function in the hippocampal mossy fiber system. Morphological studies demonstrated that fasciculation and laminar growth of mossy fibers were strongly affected, leading to innervation of CA3 pyramidal cells at ectopic sites, whereas individual mossy fiber boutons appeared normal. Electrophysiological recordings performed in hippocampal slice preparations revealed that both basal synaptic transmission and two forms of short-term plasticity, i.e., paired-pulse facilitation and frequency facilitation, were normal in mice lacking all forms of NCAM. However, long-term potentiation of glutamatergic excitatory synapses after brief trains of repetitive stimulation was abolished. Taken together, these results strongly suggest that in the hippocampal mossy fiber system, NCAM is essential both for correct axonal growth and synaptogenesis and for long-term changes in synaptic strength.}, Author = {Cremer, H. and Chazal, G. and Carleton, A. and Goridis, C. and Vincent, J. D. and Lledo, P. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Research Support, Non-U.S. Gov't;Neural Cell Adhesion Molecules;Long-Term Potentiation;Animals;Synapses;In Vitro;Neuronal Plasticity;Synaptic Transmission;Synaptophysin;Axons;Hippocampus;Mice, Inbred C57BL;Mental Disorders;Mice, Knockout;Mice;24 Pubmed search results 2008;Nerve Fibers;Learning Disorders}, Medline = {99007299}, Month = {10}, Nlm_Id = {7505876}, Number = {22}, Organization = {Developmental Biology Institute of Marsaille, Centre National de la Recherche Scientifique, Marseille Cedex 9, France.}, Pages = {13242-7}, Pubmed = {9789073}, Title = {Long-term but not short-term plasticity at mossy fiber synapses is impaired in neural cell adhesion molecule-deficient mice}, Uuid = {C071967B-1786-48FE-B370-C62AF5EC7042}, Volume = {95}, Year = {1998}} @article{Crespel:2005, Abstract = {An increased neurogenesis is reported in animal models of mesial temporal lobe epilepsy (MTLE) but the fate of newborn cells is unknown. Here, we attempted to demonstrate neurogenesis in adult epileptic tissue obtained after hippocampectomy. MTLE hippocampi showed increased expression of division markers and of Musashi-1, a marker of neural progenitors, compared to control hippocampi. Large quantities of Musashi-1(+) cells were obvious in the subgranular layer and the subventricular zone, both known neurogenic areas, and in the fissura hippocampi. Musashi-1 was expressed by small cells that were mainly vimentin(+) or nestin(+), rarely Dcx(+) or PSA-NCAM(+) and negative for markers of mature neurons or astrocytes. Some of them are present in the granular layer, the hilus, and CA1 area resembling the ectopic positions described in rodents. These findings demonstrate that neural progenitors proliferate in chronic epilepsy and suggest that the fissura hippocampi behaves like another neurogenic area.}, Author = {Crespel, Arielle and Rigau, Val{\'e}rie and Coubes, Philippe and Rousset, Marie Claude and de Bock, Fr{\'e}d{\'e}ric and Okano, Hideyuki and Baldy-Moulinier, Michel and Bockaert, Jo{\"e}l and Lerner-Natoli, Mireille}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0969-9961}, Journal = {Neurobiol Dis}, Keywords = {24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {9500169}, Number = {3}, Organization = {Institut de G{\'e}nomique Fonctionnelle, CNRS UMR 5023-INSERM U661, UM1-UM2, 141 rue de la Cardonille, F-34094 Montpellier Cedex 5, France; Unit{\'e} M{\'e}dico-chirurgicale de l'Epilepsie, H\^{o}pital Gui de Chauliac, 80 av Fliche, 34295 Montpellier Cedex 05, France.}, Pages = {436-50}, Pii = {S0969-9961(05)00035-5}, Pubmed = {16023586}, Title = {Increased number of neural progenitors in human temporal lobe epilepsy}, Uuid = {12A24875-FBC8-4B22-9D78-430DAD66B199}, Volume = {19}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.nbd.2005.01.020}} @article{Crespo:2001, Abstract = {Combining pre-embedding parvalbumin immunostaining and post-embedding immunogold detection of GABA in the olfactory bulb, we investigated whether the parvalbumin-containing GABAergic interneurons of the external plexiform layer exclusively innervate principal cells, or whether they also establish inhibitory synapses upon GABAergic local neurons such as granule cells. Our results demonstrate that the parvalbumin-containing cells do not contact GABAergic interneurons in the neuropil of the external plexiform layer. On the contrary, their postsynaptic elements were always non-GABAergic principal cells. Although classically it has been accepted that the interneurons of the external plexiform layer could exert a disinhibitory action upon principal cells, via inhibition of GABAergic granule cells, we conclude that they exert a feedback inhibitory action directly and exclusively upon principal cells.}, Author = {Crespo, C. and Blasco-Ibanez, J. M. and Marques-Mari, A. I. and Martinez-Guijarro, F. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Neuroreport}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {11}, Organization = {Departamento de Biologia Celular, Facultad de Ciencias Biologicas, Universidad de Valencia, C/Dr. Moliner, 50, E-46100, Burjasot, Spain.}, Pages = {2553-6.}, Title = {Parvalbumin-containing interneurons do not innervate granule cells in the olfactory bulb}, Uuid = {D155E51D-EF1E-4DFB-AD9B-6FA3A4BF4858}, Volume = {12}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11496147}} @article{Crepel:2007, Abstract = {Correlated neuronal activity is instrumental in the formation of networks, but its emergence during maturation is poorly understood. We have used multibeam two-photon calcium microscopy combined with targeted electrophysiological recordings in order to determine the development of population coherence from embryonic to postnatal stages in the hippocampus. At embryonic stages (E16-E19), synchronized activity is absent, and neurons are intrinsically active and generate L-type channel-mediated calcium spikes. At birth, small cell assemblies coupled by gap junctions spontaneously generate synchronous nonsynaptic calcium plateaus associated to recurrent burst discharges. The emergence of coherent calcium plateaus at birth is controlled by oxytocin, a maternal hormone initiating labour, and progressively shut down a few days later by the synapse-driven giant depolarizing potentials (GDPs) that synchronize the entire network. Therefore, in the developing hippocampus, delivery is an important signal that triggers the first coherent activity pattern, which is silenced by the emergence of synaptic transmission.}, Author = {Cr{\'e}pel, Val{\'e}rie and Aronov, Dmitriy and Jorquera, Isabel and Represa, Alfonso and Ben-Ari, Yehezkel and Cossart, Rosa}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {21 Neurophysiology;21 Calcium imaging;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8809320}, Number = {1}, Organization = {INMED, INSERM, U29, Universit{\'e} de La M{\'e}diterran{\'e}e, Parc scientifique de Luminy, BP 13, 13273 Marseille Cedex 09, France.}, Pages = {105-20}, Pii = {S0896-6273(07)00203-6}, Pubmed = {17408581}, Title = {A parturition-associated nonsynaptic coherent activity pattern in the developing hippocampus}, Uuid = {D912D599-FFAF-47C6-A418-C533C10426F3}, Volume = {54}, Year = {2007}, url = {papers/Crépel_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.03.007}} @article{Crepel:1998, Author = {Cr{\'e}pel, V. and Congar, P. and Aniksztejn, L. and Gozlan, H. and Hammond, C. and Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0079-6123}, Journal = {Prog Brain Res}, Keywords = {Synapses;Brain Ischemia;Research Support, Non-U.S. Gov't;21 Neurophysiology;Long-Term Potentiation;Neuronal Plasticity;Calcium;Receptors, N-Methyl-D-Aspartate;Animals;24 Pubmed search results 2008;review;21 Epilepsy}, Medline = {99131175}, Nlm_Id = {0376441}, Organization = {INSERM U 29, Paris, France. crepel\@u29.cochin.inserm.fr}, Pages = {273-85}, Pubmed = {9932383}, Title = {Synaptic plasticity in ischemia: role of NMDA receptors}, Uuid = {7B4129C1-D5E6-421D-BF05-50D0D8D5361D}, Volume = {116}, Year = {1998}} @article{Crighel:1965, Author = {Crighel, E. and Kreindler, A. and Sotirescu, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Epilepsy;Electric Stimulation;21 Neurophysiology;Cats;Electrophysiology;Animals;Cerebral Cortex;24 Pubmed search results 2008;21 Epilepsy}, Medline = {66032236}, Month = {10}, Nlm_Id = {0370712}, Number = {2}, Pages = {116-27}, Pubmed = {5838159}, Title = {The onset mechanism of the epileptiform afterdischarge at neocortical level}, Uuid = {93989C11-2B5A-4755-8337-AC968640CC5B}, Volume = {13}, Year = {1965}} @article{Crino:2001, Abstract = {OBJECTIVE: Focal cortical dysplasia is characterized by disorganized cortical lamination, dysplastic and heterotopic neurons, and an association with epilepsy. The contribution that dysplastic and heterotopic neurons make to epileptogenesis in focal cortical dysplasia is unknown and the phenotype of these cells may be distinct. The authors hypothesized that the expression of genes encoding glutamatergic (glutamate [GluR] and N-methyl-D-aspartate NMDA receptors [NR]) and gamma-aminobutyric acid A receptor (GABA(A)R) subunits is distinct in dysplastic and heterotopic neurons and that changes in receptor gene expression could be defined in a cell-specific pattern. METHODS: Single immunohistochemically labeled dysplastic and heterotopic neurons were microdissected from human focal cortical dysplasia specimens obtained during epilepsy surgery. Pyramidal neurons were microdissected from postmortem control cortex and from temporal cortex without dysplasia resected during temporal lobectomy. Poly (A) messenger RNA (mRNA) from single neurons was amplified, radiolabeled, and used to probe complementary DNA (cDNA) arrays containing GluR(1-6), NR(1A,1B), NR(2A-D), and GABA(A)Ralpha(1-6), and -Rbeta(1-3) subunit cDNAS: The relative hybridization intensities of each mRNA-cDNA hybrid were quantified by phosphorimaging. RESULTS: GluR, NR, and GABA(A)R subunit mRNA expression did not differ between control neurons and nondysplastic epilepsy specimens. Expression of GluR(4), NR(2B), and NR(2C) subunit mRNA was increased, and NR(2A) and GABA(A)Rbeta(1) subunit mRNA was decreased in dysplastic compared with pyramidal and heterotopic neurons. In contrast, GABA(A)Ralpha(1), -Ralpha(2), and -Rbeta(2) as well as GluR(1) mRNA levels were reduced in both dysplastic and heterotopic neurons. CONCLUSIONS: Differential expression of GluR, NR, and GABA(A)R mRNA in dysplastic and heterotopic neurons demonstrates cell specific gene transcription changes in focal cortical dysplasia. These results suggest that dysplastic and heterotopic neurons may be pharmacologically distinct and make differential contributions epileptogenesis in focal cortical dysplasia.}, Author = {Crino, P. B. and Duhaime, A. C. and Baltuch, G. and White, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {10 Development;Receptors, Glutamate;Humans;Middle Aged;Female;RNA, Messenger;research support, non-u.s. gov't;Brain Diseases;Dissection;Male;Receptors, GABA-A;10 genetics malformation;research support, u.s. gov't, p.h.s.;Neurons;Adult;24 Pubmed search results 2008;Immunohistochemistry;Adolescent}, Month = {4}, Nlm_Id = {0401060}, Number = {7}, Organization = {Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. crinop\@mail.med.upenn.edu}, Pages = {906-13}, Pubmed = {11294928}, Title = {Differential expression of glutamate and GABA-A receptor subunit mRNA in cortical dysplasia}, Uuid = {63E9FFF8-53EA-46FC-AF7B-E57491D654D8}, Volume = {56}, Year = {2001}} @article{Crocker:2001, Abstract = {Siglecs are members of the Ig superfamily that bind to sialic acid (Sia) and are mainly expressed by cells of the hematopoietic system. Until three years ago, only four Siglecs were known, namely sialoadhesin, CD22, myelin-associated glycoprotein and CD33. Since then, a further six human CD33-related Siglecs with features of inhibitory receptors have been identified and shown to be expressed by discrete subsets of leukocytes. Recognition of Sia by these Siglecs could play a role in the regulation of the innate immune system.}, Author = {Crocker, P. R. and Varki, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1471-4906}, Journal = {Trends Immunol}, Keywords = {Animals;Antigens, Differentiation, B-Lymphocyte;Antigens, Differentiation, Myelomonocytic;Humans;Antigens, CD22;Myelin-Associated Glycoprotein;review;Antigens, CD;Models, Immunological;11 Glia;Receptors, Immunologic;Immune System;Research Support, U.S. Gov't, P.H.S.;Membrane Glycoproteins;Sialic Acids;Amino Acid Sequence;Cell Adhesion Molecules;Molecular Sequence Data;Lectins;Research Support, Non-U.S. Gov't}, Medline = {21273599}, Month = {6}, Nlm_Id = {100966032}, Number = {6}, Organization = {The Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, DD1 5EH, Dundee, UK. p.r.crocker\@dundee.ac.uk}, Pages = {337-42}, Pii = {S1471490601019305}, Pubmed = {11377294}, Title = {Siglecs, sialic acids and innate immunity}, Uuid = {974B49A6-3332-45F2-98DD-12F39E16CFC8}, Volume = {22}, Year = {2001}, url = {papers/Crocker_TrendsImmunol2001.pdf}} @article{Croquelois:2008, Abstract = {In human, neuronal migration disorders are commonly associated with developmental delay, mental retardation, and epilepsy. We describe here a new mouse mutant that develops a heterotopic cortex (HeCo) lying in the dorsolateral hemispheric region, between the homotopic cortex (HoCo) and subcortical white matter. Cross-breeding demonstrated an autosomal recessive transmission. Birthdating studies and immunochemistry for layer-specific markers revealed that HeCo formation was due to a transit problem in the intermediate zone affecting both radially and tangentially migrating neurons. The scaffold of radial glial fibers, as well as the expression of doublecortin is not altered in the mutant. Neurons within the HeCo are generated at a late embryonic age (E18) and the superficial layers of the HoCo have a correspondingly lower cell density and layer thickness. Parvalbumin immunohistochemistry showed the presence of gamma-aminobutyric acidergic cells in the HeCo and the mutant mice have a lowered threshold for the induction of epileptic seizures. The mutant showed a developmental delay but, in contrast, memory function was relatively spared. Therefore, this unique mouse model resembles subcortical band heterotopia observed in human. This model represents a new and rare tool to better understand cortical development and to investigate future therapeutic strategies for refractory epilepsy.}, Author = {Croquelois, and Giuliani, and Savary, and Kielar, and Amiot, and Schenk, and Welker,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1460-2199}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {9110718}, Organization = {Service de Neuropsychologie et de Neuror{\'e}habilitation, Centre Hospitalier Universitaire Vaudois (CHUV), Avenue Pierre Decker 5, 1011 Lausanne, Switzerland.}, Pii = {bhn106}, Pubmed = {18562329}, Title = {Characterization of the HeCo Mutant Mouse: A New Model of Subcortical Band Heterotopia Associated with Seizures and Behavioral Deficits}, Uuid = {590E78D6-E64D-4866-9EC5-8941E9D316DE}, Year = {2008}, url = {papers/Croquelois_CerebCortex2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhn106}} @article{Crowe:1995, Abstract = {There are a number of machanisms by which HIV-infected macrophages contribute to the pathogenesis of the Acquired Immunodeficiency Syndrome (AIDS). Macrophage-tropic strains of HIV are present at the time of infection, and persist throughout the course of infection, despite the emergence of T cell tropic quasispecies. As HIV causes chronic infection of macrophages with only minimal cytopathology, these cells can provide an important viral reservoir in HIV-infected persons. Macrophages are more susceptible to HIV infection than freshly isolated monocytes. HIV-infected macrophages can contribute to CD4 T lymphocyte depletion through a gp120-CD4 dependent fusion process with uninfected CD4-expressing T cells. Increasing data support the role of HIV-infected macrophages and microglia in the pathogenesis of HIV-related encephalopathy and AIDS-related dementia through the production of neurotoxins. HIV infection of macrophages in vitro results in impairment of many aspects of their function. Reduced phagocytic capacity for certain opportunistic pathogens, including Toxoplasma gondii and Candida albicans, may be responsible for reactivation of these pathogens in persons with advanced HIV infection, although the mechanisms underlying reactivation of infections and susceptibility to disease from new infections are likely to be multifactorial. Our studies showing defective phagocytosis and killing provide additional information that contribute to our understanding of the pathogenesis of AIDS. Studies of in vitro efficacy of potential antiretroviral therapies should be performed in both primary lymphocyte and monocyte cultures, given the importance of both of these cell populations to HIV pathogenesis and their differing biology.}, Author = {Crowe, S. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0004-8291}, Journal = {Aust N Z J Med}, Keywords = {Research Support, Non-U.S. Gov't;HIV Infections;AIDS-Related Opportunistic Infections;AIDS Dementia Complex;CD4 Lymphocyte Count;CD4-Positive T-Lymphocytes;11 Glia;review, tutorial;Macrophages;Humans;HIV;Phagocytosis;review}, Medline = {96366176}, Month = {12}, Nlm_Id = {1264322}, Number = {6}, Organization = {AIDS Pathogenesis Research Unit, Macfarlane Burnet Centre for Medical Research, Melbourne.}, Pages = {777-83}, Pubmed = {8770353}, Title = {Role of macrophages in the pathogenesis of human immunodeficiency virus (HIV) infection}, Uuid = {A2D09029-1D9D-4721-BF46-C2FBE6A3D4BD}, Volume = {25}, Year = {1995}} @article{Cruikshank:2007, Abstract = {The thalamus provides fundamental input to the neocortex. This input activates inhibitory interneurons more strongly than excitatory neurons, triggering powerful feedforward inhibition. We studied the mechanisms of this selective neuronal activation using a mouse somatosensory thalamocortical preparation. Notably, the greater responsiveness of inhibitory interneurons was not caused by their distinctive intrinsic properties but was instead produced by synaptic mechanisms. Axons from the thalamus made stronger and more frequent excitatory connections onto inhibitory interneurons than onto excitatory cells. Furthermore, circuit dynamics allowed feedforward inhibition to suppress responses in excitatory cells more effectively than in interneurons. Thalamocortical excitatory currents rose quickly in interneurons, allowing them to fire action potentials before significant feedforward inhibition emerged. In contrast, thalamocortical excitatory currents rose slowly in excitatory cells, overlapping with feedforward inhibitory currents that suppress action potentials. These results demonstrate the importance of selective synaptic targeting and precise timing in the initial stages of neocortical processing.}, Author = {Cruikshank, Scott J. and Lewis, Timothy J. and Connors, Barry W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;21 Activity-development;research support, u.s. gov't, non-p.h.s.;21 Circuit structure-function;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {Department of Neuroscience, Division of Biology & Medicine, Box G-LN, Brown University, Providence, Rhode Island 02912, USA.}, Pages = {462-8}, Pii = {nn1861}, Pubmed = {17334362}, Title = {Synaptic basis for intense thalamocortical activation of feedforward inhibitory cells in neocortex}, Uuid = {9A1B7549-5A2E-4349-92D8-AB5150B19398}, Volume = {10}, Year = {2007}, url = {papers/Cruikshank_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1861}} @article{Cubells:1994, Abstract = {Methamphetamine (MA) produces selective degeneration of dopamine (DA) neuron terminals without cell body loss. While excitatory amino acids (EAAs) contribute to MA toxicity, terminal loss is not characteristic of excitotoxic lesions nor is excitotoxicity selective for DA fibers; rather, EAAs may modulate MA-induced DA turnover, suggesting that DA-dependent events play a key role in MA neurotoxicity. To examine this possibility, we used postnatal ventral midbrain DA neuron cultures maintained under continuous EAA blockade. As in vivo, MA caused neurite degeneration but minimal cell death. We found that MA is a vacuologenic weak base that induces swelling of endocytic compartments; MA also induces blebbing of the plasma membrane. However, these morphological changes occurred in MA-treated cultures lacking DA neurons. Therefore, while collapse of endosomal and lysosomal pH gradients and vacuolation may contribute to MA neurotoxicity, this does not explain selective DA terminal degeneration. Alternatively, MA could exert its neurotoxic effects by collapsing synaptic vesicle proton gradients and redistributing DA from synaptic vesicles to the cytoplasm. This could cause the formation of DA-derived free radicals and reactive metabolites. To test whether MA induces oxidative stress within living DA neurons, we used 2,7-dichlorofluorescin diacetate (DCF), an indicator of intracellular hydroperoxide production. MA dramatically increased the number of DCF-labeled cells in ventral midbrain cultures, which contain about 30\%DA neurons, but not in nucleus accumbens cultures, which do not contain DA neurons. In the DA neuron cultures, intracellular DDF labeling was localized to axonal varicosities, blebs, and endocytic organelles. These results suggest that MA redistributes DA from the reducing environment within synaptic vesicles to extravesicular oxidizing environments, thus generating oxygen radicals and reactive metabolites within DA neurons that may trigger selective DA terminal loss.}, Author = {Cubells, J. F. and Rayport, S. and Rajendran, G. and Sulzer, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Methamphetamine;Dopamine;Neurotoxins;Astrocytes;Organelles;Animals;Rats;Vacuoles;Oxygen;Cells, Cultured;Biological Transport;Fluoresceins;Free Radicals;Synaptic Vesicles;Neurites;Ventral Tegmental Area;Not relevant;Substantia Nigra;Kinetics;Time Factors;11 Glia;Animals, Newborn;Endocytosis;Neurons;Support, U.S. Gov't, P.H.S.;Cell Death}, Medline = {94210059}, Month = {4}, Nlm_Id = {8102140}, Number = {4}, Organization = {Department of Psychiatry, Columbia University, New York, New York 10032.}, Pages = {2260-71}, Pubmed = {8158268}, Title = {Methamphetamine neurotoxicity involves vacuolation of endocytic organelles and dopamine-dependent intracellular oxidative stress}, Uuid = {2E5F4322-E0F2-4960-AE30-4397822F9357}, Volume = {14}, Year = {1994}, url = {papers/Cubells_JNeurosci1994.pdf}} @article{Cucchiarini:2003, Abstract = {Microglia represent a crucial cell population in the central nervous system, participating in the regulation and surveillance of physiological processes as well as playing key roles in the etiologies of several major brain disorders. The ability to target gene transfer vehicles selectively to microglia would provide a powerful new approach to investigations of mechanisms regulating brain pathologies, as well as enable the development of novel therapeutic strategies. In this study, we evaluate the feasibility of specifically and efficiently targeting microglia relative to other brain cells, using vectors based on two different serotypes of adeno-associated virus (AAV) carrying cell-type-specific transcriptional elements to regulate gene expression. Among a set of promoter choices examined, an element derived from the gene for the murine macrophage marker F4/80 was the most discriminating for microglia. Gene expression from vectors controlled by this element was highly selective for microglia, both in vitro and in vivo. To our knowledge, this is the first demonstration of selective expression of transferred genes in microglia using AAV-derived vectors, as well as the first utilization of recombinant AAV-5 vectors in any macrophage lineage. These results provide strong encouragement for the application of these vectors and this approach for delivering therapeutic and other genes selectively to microglia.}, Author = {Cucchiarini, M. and Ren, X. L. and Perides, G. and Terwilliger, E. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Transduction, Genetic;Macrophages, Alveolar;Gene Targeting;Humans;Rats;Animals;Dependovirus;Brain;Microglia;Rats, Sprague-Dawley;11 Glia;Brain Diseases;Male;Genetic Vectors;Research Support, U.S. Gov't, P.H.S.;Genetic Engineering;Gene Therapy;Serotyping;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {22578074}, Month = {4}, Nlm_Id = {9421525}, Number = {8}, Organization = {Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center, Boston, MA, USA.}, Pages = {657-67}, Pii = {3301925}, Pubmed = {12692594}, Title = {Selective gene expression in brain microglia mediated via adeno-associated virus type 2 and type 5 vectors}, Uuid = {D994EFAD-7149-4A9B-A442-02A4EAFC7BD8}, Volume = {10}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3301925}} @article{Cudmore:2004, Abstract = {Neuronal excitability has a large impact on network behavior, and plasticity in intrinsic excitability could serve as an important information storage mechanism. Here we ask whether postsynaptic excitability of layer V pyramidal neurons from primary visual cortex can be rapidly regulated by activity. Whole cell current-clamp recordings were obtained from visual cortical slices, and intrinsic excitability was measured by recording the firing response to small depolarizing test pulses. Inducing neurons to fire at high-frequency (30-40 Hz) in bursts for 5 min in the presence of synaptic blockers increased the firing rate evoked by the test pulse. This long-term potentiation of intrinsic excitability (LTP-IE) lasted for as long as we held the recording (>60 min). LTP-IE was accompanied by a leftward shift in the entire frequency versus current (F-I) curve and a decrease in threshold current and voltage. Passive neuronal properties were unaffected by the induction protocol, indicating that LTP-IE occurred through modification in voltage-gated conductances. Reducing extracellular calcium during the induction protocol, or buffering intracellular calcium with bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid, prevented LTP-IE. Finally, blocking protein kinase A (PKA) activation prevented, whereas pharmacological activation of PKA both mimicked and occluded, LTP-IE. This suggests that LTP-IE occurs through postsynaptic calcium influx and subsequent activation of PKA. Activity-dependent plasticity in intrinsic excitability could greatly expand the computational power of individual neurons.}, Author = {Cudmore, Robert H. and Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Visual Cortex;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Long-Term Potentiation;Action Potentials;research support, non-u.s. gov't ;in vitro ;Rats;Egtazic Acid;Rats, Long-Evans;Animals, Newborn;Animals;comparative study ;24 Pubmed search results 2008;Excitatory Amino Acid Antagonists;Neurons}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Biology, Volen Center for Complex Systems, Brandeis University, Waltham, MA 02454-9110, USA.}, Pages = {341-8}, Pii = {01059.2003}, Pubmed = {14973317}, Title = {Long-term potentiation of intrinsic excitability in LV visual cortical neurons}, Uuid = {86938987-03EE-4BC9-89F6-C9F6E536141D}, Volume = {92}, Year = {2004}, url = {papers/Cudmore_JNeurophysiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01059.2003}} @article{Cui:2002, Abstract = {Hematopoietic stem cells (HSCs) represent an important target for the treatment of various blood disorders. As the source of critical cells within the immune system, genetic modification of HSCs can also be used to modulate immune responses. The effectiveness of HSC-mediated gene therapy largely depends on efficient gene delivery into long-term repopulating progenitors and targeted transgene expression in an appropriate progeny of the transduced pluripotent HSCs. Self-inactivating (SIN) lentiviral vectors have been demonstrated to be capable of transducing mitotically inactive cells, including HSCs, and accommodating a nonviral promoter to control the transgene expression in transduced cells. In this study, we constructed 2 SIN lentiviral vectors, EF.GFP and DR.GFP, to express the green fluorescent protein (GFP) gene controlled solely by the promoter of either a housekeeping gene EF-1alpha or the human HLA-DRalpha gene, which is selectively expressed in antigen-presenting cells (APCs). We demonstrated that both vectors efficiently transduced human pluripotent CD34+ cells capable of engrafting nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. When the EF.GFP vector was used, constitutive high-level GFP expression was obtained in all the human HSC progeny detectable in NOD/SCID mice and in subsequent in vitro differentiation assays, indicating that engrafting human HSCs have been transduced. In contrast, the DR.GFP vector mediated transgene expression specifically in human HLA-DR+ cells and highly in differentiated dendritic cells (DCs), which are critical in regulating immunity. Furthermore, human DCs derived from transduced and engrafted human cells potently stimulated allogeneic T-cell proliferation. This study demonstrated successful targeting of transgene expression to APCs/DCs after stable gene transduction of pluripotent HSCs.}, Author = {Cui, Yan and Golob, Jonathan and Kelleher, Erin and Ye, Zhaohui and Pardoll, Drew and Cheng, Linzhao}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Cell Differentiation;Mice, SCID;Genetic Vectors;Green Fluorescent Proteins;HLA-DR Antigens;Luminescent Proteins;Feasibility Studies;Animals;Lymphocyte Activation;Genes, Synthetic;Research Support, U.S. Gov't, P.H.S.;Peptide Elongation Factor 1;Transgenes;Genes, Reporter;Promoter Regions (Genetics);Transfection;Isoantigens;Hematopoietic Stem Cells;Dendritic Cells;Spleen;Macrophages;T-Lymphocytes;11 Glia;Hematopoietic Stem Cell Transplantation;Leukocytes, Mononuclear;Gene Expression Regulation;Mice, Inbred NOD;Graft Survival;Bone Marrow Cells;Mice;Research Support, Non-U.S. Gov't;Lentivirus;Humans}, Medline = {21640012}, Month = {1}, Nlm_Id = {7603509}, Number = {2}, Organization = {Division of Immunology and Hematopoiesis, Johns Hopkins Oncology Center, Johns Hopkins University, Baltimore, MD 21231, USA.}, Pages = {399-408}, Pubmed = {11781219}, Title = {Targeting transgene expression to antigen-presenting cells derived from lentivirus-transduced engrafting human hematopoietic stem/progenitor cells}, Uuid = {A69D80D5-4118-40DC-9311-36C314F36E6C}, Volume = {99}, Year = {2002}} @article{Culic:1994, Abstract = {Experiments were performed to investigate the effects of cerebellar stimulation on epilepsy induced by parenteral administration of penicillin, in rats without or with the lesion of sensorimotor cortex. There were no differences in the EEG activity of the same experimental animal after the first and subsequent penicillin treatments (at least 7 days later). The electrical stimulation (duration of 5-10 min) of the lateral cerebellar nucleus was applied repetitively 135-315 min after penicillin administration, when the EEG power spectra markedly increased. The cerebellar stimulation evoked the decrease of the mean total EEG power spectra, but the effects were temporary. The EEG power spectra were significantly lower (P < 0.05) during the period of 150-330 min after penicillin treatment in experimental sessions with applied cerebellar stimulation in comparison to the experimental sessions without such stimulation. The residual effects (if any) of cerebellar stimulation on the EEG activity in the later period, 345-600 after penicillin treatment were not significant (P > 0.05). Cerebellar stimulation had the same effect among unlesioned animals and animals with prior cortical lesion in the acute model of epilepsy.}, Author = {Culic, M. and Saponjic, J. and Jankovic, B. and Rakic, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0971-5916}, Journal = {Indian J Med Res}, Keywords = {Electric Stimulation;Penicillins;Electroencephalography;Research Support, Non-U.S. Gov't;Epilepsy;21 Neurophysiology;24 Pubmed search results 2008;Rats;21 Epilepsy;Rats, Wistar;Animals;Disease Models, Animal;Cerebral Cortex;Cerebellar Nuclei;Male}, Medline = {95048604}, Month = {9}, Nlm_Id = {0374701}, Organization = {Institute for Biological Research, Center for Multidisciplinary Studies, Belgrade, Yugoslavia.}, Pages = {135-9}, Pubmed = {7959970}, Title = {Effect of cerebellar stimulation on EEG power spectra in the acute model of epilepsy}, Uuid = {54CAFF0B-98E9-4626-A7FE-8B7AE58D65C3}, Volume = {100}, Year = {1994}} @article{Culic:1995, Abstract = {The experiments were performed in order to investigate the sparing of function following early postnatal cortical lesion in the acute rat model of epilepsy. Sensorimotor cortex was unilaterally removed at 9 and 10 days of postnatal age in lesioned animals, while control animals were only sham operated (at the same early stage of life) or non-operated (before implantation of the electrodes). Seizure activity was recorded by means of electroencephalograms at adult stage of life induced by parenteral administration of penicillin (1,000,000 I.U./kg, i.p.). Our results showed that when the cortical lesion was performed in infancy (on the contrary to the lesion performed in adulthood) there was no prolongation of seizure activity in an acute model of epilepsy.}, Author = {Culi\'{c}, M. and Saponji\'{c}, J. and Jankovi\'{c}, B. and Pekovi\'{c}, S. and Stojiljkovi\'{c}, M. and Udovi\'{c}, S. and Raki\'{c}, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0736-5748}, Journal = {Int J Dev Neurosci}, Keywords = {Penicillins;Aging;Prognosis;Research Support, Non-U.S. Gov't;Neuroprotective Agents;Epilepsy;Electroencephalography;Rats;21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy;Rats, Wistar;Male;Injections, Intraperitoneal;Cerebral Cortex;Animals;Disease Models, Animal}, Medline = {96104002}, Month = {10}, Nlm_Id = {8401784}, Number = {6}, Organization = {Institute for Biological Research, University of Belgrade, Serbia Montenegro.}, Pages = {655-8}, Pii = {0736574895000218}, Pubmed = {8553901}, Title = {Effect of early cortical lesion on the acute model of epilepsy}, Uuid = {3A325323-445A-4004-A9E9-0F264B2F3F11}, Volume = {13}, Year = {1995}} @article{Cumming:2007, Abstract = {Error bars commonly appear in figures in publications, but experimental biologists are often unsure how they should be used and interpreted. In this article we illustrate some basic features of error bars and explain how they can help communicate data and assist correct interpretation. Error bars may show confidence intervals, standard errors, standard deviations, or other quantities. Different types of error bars give quite different information, and so figure legends must make clear what error bars represent. We suggest eight simple rules to assist with effective use and interpretation of error bars.}, Author = {Cumming, Geoff and Fidler, Fiona and Vaux, David L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {24 Pubmed search results 2008;23 Technique}, Month = {4}, Nlm_Id = {0375356}, Number = {1}, Organization = {School of Psychological Science and 2Department of Biochemistry, La Trobe University, Melbourne, Victoria, Australia 3086. g.cumming\@latrobe.edu.au}, Pages = {7-11}, Pii = {jcb.200611141}, Pubmed = {17420288}, Title = {Error bars in experimental biology}, Uuid = {38B5F7B4-962A-4786-895E-FBDC19CD9F0E}, Volume = {177}, Year = {2007}, url = {papers/Cumming_JCellBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200611141}} @article{Cunto:2002, Abstract = {During spermatogenesis, the first morphological indication of spermatogonia differentiation is incomplete cytokinesis, followed by the assembly of stable intercellular cytoplasmic communications. This distinctive feature of differentiating male germ cells has been highly conserved during evolution, suggesting that regulation of the cytokinesis endgame is a crucial aspect of spermatogenesis. However, the molecular mechanisms underlying testis-specific regulation of cytokinesis are still largely unknown. Citron kinase is a myotonin-related protein acting downstream of the GTPase Rho in cytokinesis control. We previously reported that Citron kinase knockout mice are affected by a complex neurological syndrome caused by cytokinesis block and apoptosis of specific neuronal precursors. In this report we show that, in addition, these mice display a dramatic testicular impairment, with embryonic and postnatal loss of undifferentiated germ cells and complete absence of mature spermatocytes. By contrast, the ovaries of mutant females appear essentially normal. Developmental analysis revealed that the cellular depletion observed in mutant testes is caused by increased apoptosis of undifferentiated and differentiating precursors. The same cells display a severe cytokinesis defect, resulting in the production of multinucleated cells and apoptosis. Our data indicate that Citron kinase is specifically required for cytokinesis of the male germ line. 0021-9533 Journal Article}, Author = {Cunto, F. D. and Imarisio, S. and Camera, P. and Boitani, C. and Altruda, F. and Silengo, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Cell Sci}, Keywords = {Spermatocytes/*cytology;In Situ Nick-End Labeling;Testis/cytology/enzymology/growth &development;05 Citron Kinase flathead;Mice, Knockout;Immunohistochemistry;Cell Cycle/*physiology;CK;Protein-Serine-Threonine Kinases/genetics/*physiology;Support, Non-U.S. Gov't;Animals;Male;Mice}, Number = {Pt 24}, Organization = {Department of Genetics, Biology and Biochemistry, Via Santena 5 bis, Torino, Italy. ferdinando.dicunto\@unito.it}, Pages = {4819-26}, Pubmed = {12432070}, Title = {Essential role of citron kinase in cytokinesis of spermatogenic precursors}, Uuid = {831222AB-90D7-4800-A0EE-E566CA5A25A2}, Volume = {115}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12432070}} @article{Curtis:2007, Abstract = {During brain development, one of the most important structures is the subventricular zone (SVZ), from which most neurons are generated. In adulthood the SVZ maintains a pool of progenitor cells that continuously replace neurons in the olfactory bulb. Neurodegenerative diseases induce a substantial upregulation or downregulation of SVZ progenitor cell proliferation, depending on the type of disorder. Far from being a dormant layer, the SVZ responds to neurodegenerative disease in a way that makes it a potential target for therapeutic intervention.}, Author = {Curtis, Maurice A. and Faull, Richard L. M. and Eriksson, Peter S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {research support, non-u.s. gov't;Neurodegenerative Diseases;Lateral Ventricles;Animals;Humans;24 Pubmed search results 2008;Neurons;review}, Month = {9}, Nlm_Id = {100962781}, Number = {9}, Organization = {Institute of Neuroscience and Physiology at Sahlgrenska Academy, Medicinaregat 11, Box 432, s-40530 G{\"o}teborg, Sweden. maurice.curtis\@neuro.gu.se}, Pages = {712-23}, Pii = {nrn2216}, Pubmed = {17704813}, Title = {The effect of neurodegenerative diseases on the subventricular zone}, Uuid = {2B9851EE-8704-4BD0-9FD1-C31C21DF7D35}, Volume = {8}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2216}} @article{Curtis:2003, Abstract = {Neurogenesis has recently been observed in the adult human brain, suggesting the possibility of endogenous neural repair. However, the augmentation of neurogenesis in the adult human brain in response to neuronal cell loss has not been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the subependymal layer (SEL) adjacent to the caudate nucleus in the human brain in response to neurodegeneration of the caudate nucleus in Huntington's disease (HD). Postmortem control and HD human brain tissue were examined by using the cell cycle marker proliferating cell nuclear antigen (PCNA), the neuronal marker beta III-tubulin, and the glial cell marker glial fibrillary acidic protein (GFAP). We observed a significant increase in cell proliferation in the SEL in HD compared with control brains. Within the HD group, the degree of cell proliferation increased with pathological severity and increasing CAG repeats in the HD gene. Most importantly, PCNA+ cells were shown to coexpress beta III-tubulin or GFAP, demonstrating the generation of neurons and glial cells in the SEL of the diseased human brain. Our results provide evidence of increased progenitor cell proliferation and neurogenesis in the diseased adult human brain and further indicate the regenerative potential of the human brain.}, Author = {Curtis, Maurice A. and Penney, Ellen B. and Pearson, Andree G. and van Roon-Mom, Willeke M. C. and Butterworth, Niqi J. and Dragunow, Michael and Connor, Bronwen and Faull, Richard L. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Minisatellite Repeats;Trinucleotide Repeats;Glial Fibrillary Acidic Protein;Aged;Research Support, Non-U.S. Gov't;Case-Control Studies;Nerve Regeneration;Tubulin;Adult;Proliferating Cell Nuclear Antigen;06 Adult neurogenesis injury induced;Cell Division;Middle Aged;Huntington Disease;Humans;Brain}, Medline = {22758992}, Month = {7}, Nlm_Id = {7505876}, Number = {15}, Organization = {Department of Anatomy with Radiology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland, New Zealand.}, Pages = {9023-7}, Pii = {1532244100}, Pubmed = {12853570}, Title = {Increased cell proliferation and neurogenesis in the adult human Huntington's disease brain}, Uuid = {CE947B36-E6A7-4BBF-A6A8-936CF6E73020}, Volume = {100}, Year = {2003}, url = {papers/Curtis_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1532244100}} @article{Czeh:2001, Abstract = {Stress-induced structural remodeling in the adult hippocampus, involving debranching and shortening of dendrites and suppression of neurogenesis, provides a cellular basis for understanding the impairment of neural plasticity in the human hippocampus in depressive illness. Accordingly, reversal of structural remodeling may be a desirable goal for antidepressant therapy. The present study investigated the effect of tianeptine, a modified tricyclic antidepressant, in the chronic psychosocial stress model of adult male tree shrews (Tupaia belangeri), a model with high validity for research on the pathophysiology of major depression. Animals were subjected to a 7-day period of psychosocial stress to elicit stress-induced endocrine and central nervous alterations before the onset of daily oral administration of tianeptine (50 mg/kg). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy, cell proliferation in the dentate gyrus was quantified by using BrdUrd immunohistochemistry, and hippocampal volume was measured post mortem. Chronic psychosocial stress significantly decreased in vivo concentrations of N-acetyl-aspartate (-13\%), creatine and phosphocreatine (-15\%), and choline-containing compounds (-13\%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (-33\%). These stress effects were prevented by the simultaneous administration of tianeptine yielding normal values. In stressed animals treated with tianeptine, hippocampal volume increased above the small decrease produced by stress alone. These findings provide a cellular and neurochemical basis for evaluating antidepressant treatments with regard to possible reversal of structural changes in brain that have been reported in depressive disorders.}, Author = {Czeh, B. and Michaelis, T. and Watanabe, T. and Frahm, J. and de Biurrun, G. and van Kampen, M. and Bartolomucci, A. and Fuchs, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:44 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {C pdf;04 Adult neurogenesis factors}, Number = {22}, Organization = {Division of Neurobiology, German Primate Center, 37077 Gottingen, Germany; and Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut fur biophysikalische Chemie, 37070 Gottingen, Germany.}, Pages = {12796-801.}, Title = {Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine}, Uuid = {5E856E0C-82FD-4BC6-BFBE-2E722CFBF907}, Volume = {98}, Year = {2001}, url = {papers/Czeh_ProcNatlAcadSciUSA2001.pdf}} @article{DAgostino:2002, Abstract = {Subcortical band heterotopia (SBH) or double cortex syndrome is a neuronal migration disorder, which occurs very rarely in males: to date, at least 110 females but only 11 in males have been reported. The syndrome is usually associated with mutations in the doublecortin (DCX) (Xq22.3-q23) gene, and much less frequently in the LIS1 (17p13.3) gene. To determine whether the phenotypic spectrum, the genetic basis and genotype-phenotype correlations of SBH in males are similar to those in females, we compared the clinical, imaging and molecular features in 30 personally evaluated males and 60 previously reported females with SBH. Based on the MRI findings, we defined the following band subtypes: partial, involving one or two cerebral lobes; intermediate, involving two lobes and a portion of a third; diffuse, with substantial involvement of three or more lobes; and pachygyria-SBH, in which posterior SBH merges with anterior pachygyria. Karyo typing and mutation analysis of DCX and/or LIS1 were performed in 23 and 24 patients, respectively. The range of clinical phenotypes in males with SBH greatly overlapped that in females. MRI studies revealed that some anatomical subtypes of SBH, such as partial and intermediate posterior, pachygyria-SBH and diffuse bands with posterior predominance, were more frequently or exclusively present in males. Conversely, classical diffuse SBH and diffuse bands with anterior predominance were more frequent in females. Males had either mild or the most severe band subtypes, and these correlated with the over-representation of normal/borderline intelligence and severe mental retardation, respectively. Conversely, females who had predominantly diffuse bands exhibited mostly mild or moderate mental retardation. Seven patients (29\%) had missense mutations in DCX; in four, these were germline mutations, whereas in three there was evidence for somatic mosaicism. A germline missense mutation of LIS1 and a partial trisomy of chromosome 9p were identified in one patient (4\%) each. One male each had a possible pathogenic intronic base change in both DCX and LIS1 genes. Our study shows that SBH in males is a clinically heterogeneous syndrome, mostly occurring sporadically. The clinical spectrum is similar to that of females with SBH. However, the greater cognitive and neuroradiological heterogeneity and the small number of mutations identified to date in the coding sequences of the DCX and LIS1 genes in males differ from the findings in females. This suggests other genetic mechanisms such as mutations in the non-coding regions of the DCX or LIS1 genes, gonadal or somatic mosaicism, and finally mutations of other genes.}, Author = {D'Agostino, Maria Daniela and Bernasconi, Andrea and Das, Soma and Bastos, Alexandre and Valerio, Rosa M. and Palmini, Andr{\'e} and Costa da Costa, Jaderson and Scheffer, Ingrid E. and Berkovic, Samuel and Guerrini, Renzo and Dravet, Charlotte and Ono, Jiro and Gigli, GianLuigi and Federico, Antonio and Booth, Fran and Bernardi, Bruno and Volpi, Lilia and Tassinari, Carlo Alberto and Guggenheim, Mary Anne and Ledbetter, David H. and Gleeson, Joseph G. and Lopes-Cendes, Iscia and Vossler, David G. and Malaspina, Elisabetta and Franzoni, Emilio and Sartori, Roberto J. and Mitchell, Michael H. and Mercho, Suha and Dubeau, Fran\c{c}ois and Andermann, Frederick and Dobyns, William B. and Andermann, Eva}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0006-8950}, Journal = {Brain}, Keywords = {Microtubule-Associated Proteins;10 Development;Magnetic Resonance Imaging;Pregnancy;Child, Preschool;Humans;comparative study;Phenotype;1-Alkyl-2-acetylglycerophosphocholine Esterase;Female;Mutation;Infant;Child;21 Dysplasia-heterotopia;Cell Movement;research support, non-u.s. gov't;Male;Neuropeptides;Nervous System Malformations;10 genetics malformation;21 Neurophysiology;Cerebral Cortex;Neurons;Sex Characteristics;Adult;Genotype;24 Pubmed search results 2008;Choristoma;Adolescent}, Month = {11}, Nlm_Id = {0372537}, Number = {Pt 11}, Organization = {Department of Neurology and Neurosurgery, and the Montreal Neurological Institute and Hospital, Quebec, Canada.}, Pages = {2507-22}, Pubmed = {12390976}, Title = {Subcortical band heterotopia (SBH) in males: clinical, imaging and genetic findings in comparison with females}, Uuid = {7F4AF764-DB6D-4647-A71F-04BFCD0BD1F0}, Volume = {125}, Year = {2002}, url = {papers/D'Agostino_Brain2002.pdf}} @article{DAmour:2003, Abstract = {Stem cells (SCs) are functionally defined by their abilities to self-renew and generate differentiated cells. Although much effort has been focused on defining the common characteristics among various types of SCs, the genetic and functional differences between multipotent and pluripotent SCs have garnered less attention. We report a direct genetic and functional comparison of molecularly defined and clonally related populations of neural SCs (NSCs) and embryonic SCs (ESCs), using the Sox2 promoter for isolation of purified populations by fluorescence-activated cell sorting. A stringent expression profile comparison of promoter-defined NSCs and ESCs revealed a striking dissimilarity, and subsequent chimera analyses confirmed the fundamental differences in cellular potency between these populations. This direct comparison elucidates the molecular basis for the functional differences in pluripotent ESCs and multipotent NSCs. 0027-8424 Journal Article}, Author = {D'Amour, K. A. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {DNA, Complementary/genetics;DNA-Binding Proteins/genetics;Animals;Base Sequence;Comparative Study;Chimeric Proteins/genetics;Mice, Transgenic;Pluripotent Stem Cells/*cytology/*physiology;Nuclear Proteins/genetics;Gene Expression Profiling;Reverse Transcriptase Polymerase Chain Reaction;04 Adult neurogenesis factors;Multipotent Stem Cells/*cytology/*physiology;Neurons/*chemistry/*physiology;Promoter Regions (Genetics);Mice;C pdf;Luminescent Proteins/genetics}, Organization = {Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.}, Pages = {11866-72}, Pubmed = {12923297}, Title = {Genetic and functional differences between multipotent neural and pluripotent embryonic stem cells}, Uuid = {57AEB715-82A8-441F-9D56-7AF4A8745939}, Volume = {100 Suppl 1}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12923297}} @article{DAntuono:2004, Abstract = {Patients with Taylor's type focal cortical dysplasia (FCD) present with seizures that are often medically intractable. Here, we attempted to identify the cellular and pharmacological mechanisms responsible for this epileptogenic state by using field potential and K+-selective recordings in neocortical slices obtained from epileptic patients with FCD and, for purposes of comparison, with mesial temporal lobe epilepsy (MTLE), an epileptic disorder that, at least in the neocortex, is not characterized by any obvious structural aberration of neuronal networks. Spontaneous epileptiform activity was induced in vitro by applying 4-aminopyridine (4AP)-containing medium. Under these conditions, we could identify in FCD slices a close temporal relationship between ictal activity onset and the occurrence of slow interictal-like events that were mainly contributed by GABAA receptor activation. We also found that in FCD slices, pharmacological procedures capable of decreasing or increasing GABAA receptor function abolished or potentiated ictal discharges, respectively. In addition, the initiation of ictal events in FCD tissue coincided with the occurrence of GABAA receptor-dependent interictal events leading to [K+]o elevations that were larger than those seen during the interictal period. Finally, by testing the effects induced by baclofen on epileptiform events generated by FCD and MTLE slices, we discovered that the function of GABAB receptors (presumably located at presynaptic inhibitory terminals) was markedly decreased in FCD tissue. Thus, epileptiform synchronization leading to in vitro ictal activity in the human FCD tissue is initiated by a synchronizing mechanism that paradoxically relies on GABAA receptor activation causing sizeable increases in [K+]o. This mechanism may be facilitated by the decreased ability of GABAB receptors to control GABA release from interneuron terminals.}, Author = {D'Antuono, M. and Louvel, J. and K{\"o}hling, R. and Mattia, D. and Bernasconi, A. and Olivier, A. and Turak, B. and Devaux, A. and Pumain, R. and Avoli, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0006-8950}, Journal = {Brain}, Keywords = {Adolescent;10 Development;in vitro;Electrophysiology;Epilepsies, Partial;Humans;Neocortex;Female;Homeostasis;Child;Baclofen;research support, non-u.s. gov't;Male;Analysis of Variance;Potassium;Receptors, GABA-A;Potassium Channel Blockers;Epilepsy, Temporal Lobe;10 genetics malformation;Adult;24 Pubmed search results 2008;4-Aminopyridine;Receptors, N-Methyl-D-Aspartate;GABA Agonists}, Month = {7}, Nlm_Id = {0372537}, Number = {Pt 7}, Organization = {Dipartimento di Fisiologia Umana e Farmacologia V. Erspamer, Universit\`{a} degli Studi di Roma La Sapienza, Italy.}, Pages = {1626-40}, Pii = {awh181}, Pubmed = {15175227}, Title = {GABAA receptor-dependent synchronization leads to ictogenesis in the human dysplastic cortex}, Uuid = {1447F7E2-27E5-49A4-B844-C8BEF0797B4F}, Volume = {127}, Year = {2004}, url = {papers/D'Antuono_Brain2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/brain/awh181}} @article{Dal-Canto:1997, Abstract = {In many patients with AIDS, severe neurologic deficits develop that have been designated the cf2HIV-associated cognitive-motor complex. cf1 Pathologically, these symptoms correlate with a low-grade inflammatory condition, referred to as cf2HIV encephalitis,cf1 in which the most characteristic change is the presence of multinucleated giant cells. Cortical changes include neuronal loss and alterations of dendrites and synapses. There is pallor of white matter generally associated with the mononuclear inflammatory infiltrates. The only cells that seem to be directly infected by HIV are the microglia/monocyte and the giant cells derived from fusion of monocytes. It is hypothesized, therefore, that cortical and white matter alterations in patients with this syndrome depend on the production of injurious soluble factors liberated by these cells and by astrocytes under the influence of many of these same factors. This article reviews recent advances in the understanding of these secondary effects and discusses pathogenetic mechanisms of tissue injury.}, Author = {Dal Canto, M. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {1052-5149}, Journal = {Neuroimaging Clin N Am}, Keywords = {HIV Infections;Central Nervous System;AIDS Dementia Complex;11 Glia;Humans;HIV;review}, Medline = {97268964}, Month = {5}, Nlm_Id = {9211377}, Number = {2}, Organization = {Division of Neuropathology, Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, USA.}, Pages = {231-41}, Pubmed = {9113688}, Title = {Mechanisms of HIV infection of the central nervous system and pathogenesis of AIDS-dementia complex}, Uuid = {0A3F7B00-D7A7-4315-9C58-8228F5BBB4F1}, Volume = {7}, Year = {1997}} @article{Dallison:2003, Abstract = {Previous studies have shown that when the medial prefrontal cortex (mPFC) is removed at 7-10 days of age there is a spontaneous filling of the lesion cavity and a nearly complete restitution of behaviour. In the current study animals received mPFC lesions on postnatal day 10 and on day 160 the tissue occupying the mPFC region was again removed. Behavioural performance on the Morris water task was compared to animals with either only day 10 mPFC lesions or only day 160 mPFC lesions. Rats with the combined day 10 and day 160 lesions or day 160 lesions were severely impaired at the task whereas the rats with only day 10 lesions showed complete recovery. An analysis of dendritic arborization in pyramidal neurons adjacent to the lesion showed increased dendritic arborization in the basilar fields in both the P10 groups but this was not associated with functional recovery in the animals with the two mPFC lesions. It thus appears that the tissue that filled in the mPFC lesions on day 10 was functional.}, Author = {Dallison, Agnes and Kolb, Bryan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Rats, Long-Evans;Prefrontal Cortex;Silver Staining;Animals;Aging;Rats;Comparative Study;Recovery of Function;Female;Sex Factors;Behavior, Animal;Time Factors;Dendrites;Male;Animals, Newborn;Escape Reaction;Organ Size;Maze Learning;24 Pubmed search results 2008;Swimming}, Month = {11}, Nlm_Id = {8004872}, Number = {1-2}, Organization = {Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, Canada, T1K 3M4.}, Pages = {57-63}, Pii = {S0166432803003371}, Pubmed = {14643459}, Title = {Recovery from infant medial frontal cortical lesions in rats is reversed by cortical lesions in adulthood}, Uuid = {3DB831B1-15B4-4D07-A1E3-575146A8824C}, Volume = {146}, Year = {2003}} @article{Dalmau:1998, Abstract = {During the prenatal development of the hippocampus, microglial cell precursors progressively occur in all subfields in accordance with known ontogenetic gradients of the region (Dalmau et al., J. Comp. Neurol. 1997a;377:70-84). The present study follows the regional distribution of these microglial cell precursors and their morphological differentiation in the rat hippocampus from birth to postnatal (P) day 18. The results demonstrate that the cellular differentiation and the subregional distribution of microglia follow the specific developmental gradients of the different parts of Ammon's horn and the dentate gyrus. Microglial cell distribution in the dentate gyrus is thus delayed compared with that in Ammon's horn. The appearance of microglia in the hippocampal subregions and differentiation of cell precursors into adult microglia occur earlier at temporal levels than at septal levels. Distribution of microglial cells follows an outside-to-inside pattern from the hippocampal fissure to the main cell layers in either Ammon's horn or the dentate gyrus. Meanwhile, the resident microglial cells located in the stratum oriens and dentate hilus at birth also increase in number and gradually disperse throughout the whole tissue of the two layers with age. In Ammon's horn, microglial differentiation occurs earlier in CA3 than in CA1. In the dentate gyrus, microglia appear earlier in relation to the external limb than to the internal limb, largely following a lateral-to-medial gradient. The differentiation and appearance of microglia in the various hippocampal and dentate subregions often correspond to the developmental stage of intrinsic and extrinsic afferent nerve fiber projections. Finally, in both Ammon's horn and the dentate gyrus, cells resembling reactive microglia are also observed and, in particular, in the perforant path projections from P9 to P18, suggesting their participation not only in phagocytosis of dead cells but also in axonal elimination and/or fiber reorganization.}, Author = {Dalmau, I. and Finsen, B. and Zimmer, J. and Gonz{\'a}lez, B. and Castellano, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {1050-9631}, Journal = {Hippocampus}, Keywords = {Acid Anhydride Hydrolases;Cell Differentiation;Female;Hippocampus;Cell Aging;Not relevant;Rats, Wistar;Time Factors;11 Glia;Microglia;Animals, Newborn;Histocytochemistry;Rats;Animals;Male;Support, Non-U.S. Gov't;Dentate Gyrus}, Medline = {99041331}, Nlm_Id = {9108167}, Number = {5}, Organization = {Department of Cell Biology and Physiology, Universitat Aut\`{o}noma de Barcelona, Spain. i.dalmau\@cc.uab.es}, Pages = {458-74}, Pubmed = {9825958}, Title = {Development of microglia in the postnatal rat hippocampus}, Uuid = {BBAFE0C6-F320-485A-9BE5-6D809607E8B0}, Volume = {8}, Year = {1998}} @article{Dalmau:2003, Abstract = {Entrance of mesodermal precursors into the developing CNS is the most well-accepted origin of microglia. However, the contribution of proliferation and death of recruited microglial precursors to the final microglial cell population remains to be elucidated. To investigate microglial proliferation and apoptosis during development, we combined proliferating cell nuclear antigen (PCNA) immunohistochemistry, in situ detection of nuclear DNA fragmentation (TUNEL), and caspase-3 immunohistochemistry with tomato lectin histochemistry, a selective microglial marker. The study was carried out in Wistar rats from embryonic day (E) 16 to postnatal day (P) 18 in cerebral cortex, subcortical white matter, and hippocampus. Proliferating microglial cells were found at all ages in the three brain regions and represented a significant fraction of the total microglial cell population. The percentage of microglia expressing PCNA progressively increased from the embryonic period (25-51\%at E16) to a maximum at P9, when the great majority of microglia expressed PCNA (92-99\%) in all the brain regions analyzed. In spite of the remarkable proliferation and expansion of the microglial population with time, the density of microglia remained quite constant in most brain regions because of the considerable growth of the brain during late prenatal and early postnatal periods. In contrast, apoptosis of microglia was detected only at certain times and was restricted to some ameboid cells in white matter and primitive ramified cells in gray matter, representing a small fraction of the microglial population. Therefore, our results point to proliferation of microglial precursors in the developing brain as a physiological mechanism contributing to the acquisition of the adult microglial cell population. In contrast, microglial apoptosis occurs only locally at certain developmental stages and thus seems less crucial for the establishment of the final density of microglia.}, Author = {Dalmau, Ishar and Vela, Jos{\'e} Miguel and Gonz{\'a}lez, Berta and Finsen, Bente and Castellano, Bernardo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Caspases;In Situ Nick-End Labeling;Rats;Proliferating Cell Nuclear Antigen;Rats, Wistar;Cell Count;11 Glia;Microglia;Cell Division;Not relevant;Support, Non-U.S. Gov't;Brain;Phagocytosis;Animals;DNA Fragmentation}, Medline = {22483863}, Month = {3}, Nlm_Id = {0406041}, Number = {2}, Organization = {Departmet of Histology, Faculty of Medicine, Autonomous University of Barcelona, E-08193-Bellaterra, Spain.}, Pages = {144-57}, Pubmed = {12596255}, Title = {Dynamics of microglia in the developing rat brain}, Uuid = {40B43435-EC28-11DA-8617-000D9346EC2A}, Volume = {458}, Year = {2003}, url = {papers/Dalmau_JCompNeurol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10572}} @article{Dammerman:2000, Abstract = {Layer 1 of the developing rodent somatosensory cortex contains a dense, transient GABAergic fiber plexus. Axons arising from the zona incerta (ZI) of the ventral thalamus contribute to this plexus, as do axons of intrinsic GABAergic cells of layer 1. The function of this early-appearing fiber plexus is not known, but these fibers are positioned to contact the apical dendrites of most postmigratory neurons. Here we show that electrical stimulation of layer 1 results in a GABA(A)-mediated postsynaptic current (PSC) in pyramidal neurons. Gramicidin perforated patch recording demonstrates that the GABAergic layer 1 synapse is excitatory and can trigger action potentials in cortical neurons. In contrast to electrical stimulation, activation of intrinsic layer 1 neurons with a glutamate agonist fails to produce PSCs in pyramidal cells. In addition, responses can be evoked by stimulation of layer 1 at relatively large distances from the recording site. These findings are consistent with a contribution of the widely projecting incertocortical pathway, the only described GABAergic projection to neonatal cortex. Recording of identified neonatal incertocortical neurons reveals a population of active cells that exhibit high frequencies of spontaneous action potentials and are capable of robustly activating neonatal cortical neurons. Because the fiber plexus is confined to layer 1, this pathway provides a spatially restricted excitatory GABAergic innervation of the distal apical dendrites of pyramidal neurons during the peak period of cortical synaptogenesis.}, Author = {Dammerman, R. S. and Flint, A. C. and Noctor, S. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Excitatory Amino Acid Antagonists;Excitatory Postsynaptic Potentials;Rhodamines;Animals;Fluorescent Dyes;Synapses;gamma-Aminobutyric Acid;Rats;Neocortex;Patch-Clamp Techniques;2-Amino-5-phosphonovalerate;Rats, Sprague-Dawley;Pyramidal Cells;Calcium;Research Support, U.S. Gov't, P.H.S.;Action Potentials;Quinoxalines;21 Neurophysiology;Somatosensory Cortex;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {20359585}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Neurology and the Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.}, Pages = {428-34}, Pubmed = {10899216}, Title = {An excitatory GABAergic plexus in developing neocortical layer 1}, Uuid = {68DAA0F1-9D1B-4C15-8092-EAF1B2F29A2F}, Volume = {84}, Year = {2000}} @article{Daneman:2005, Abstract = {Despite the importance of the blood-brain barrier (BBB), little is known about the molecular mechanisms that control its integrity. The identification of moody, a gene required for the formation and maintenance of the Drosophila BBB, provides new insight into how paracellular junctions are formed at the barrier. Meanwhile, moody also has been identified in a screen for fly mutants with altered sensitivity to cocaine, remarkably implicating the BBB in the physiological response to narcotics.}, Author = {Daneman, Richard and Barres, Ben A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008;10 Development;Neuroglia;Blood-Brain Barrier;Cell Adhesion Molecules;Drosophila Proteins;Signal Transduction;Tight Junctions;Animals;Endothelial Cells;Humans;Receptors, G-Protein-Coupled;review}, Month = {10}, Nlm_Id = {0413066}, Number = {1}, Organization = {Department of Neurobiology, Stanford University School of Medicine, CA 94305, USA. rdaneman\@stanford.edu}, Pages = {9-12}, Pii = {S0092-8674(05)00970-0}, Pubmed = {16213208}, Title = {The blood-brain barrier--lessons from moody flies}, Uuid = {9F1CE65B-675C-4D6C-94E8-C981493AA296}, Volume = {123}, Year = {2005}, url = {papers/Daneman_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.09.017}} @article{Dani:2005, Abstract = {Rett Syndrome (RTT) is a devastating neurological disorder that is caused by mutations in the MECP2 gene. Mecp2-mutant mice have been used as a model system to study the disease mechanism. Our previous work has suggested that MeCP2 malfunction in neurons is the primary cause of RTT in the mouse. However, the neurophysiological consequences of MeCP2 malfunction remain obscure. Using whole-cell patch-clamp recordings in cortical slices, we show that spontaneous activity of pyramidal neurons is reduced in Mecp2-mutant mice. This decrease is not caused by a change in the intrinsic properties of the recorded neurons. Instead, the balance between cortical excitation and inhibition is shifted to favor inhibition over excitation. Moreover, analysis of the miniature excitatory postsynaptic currents (mEPSCs)/inhibitory postsynaptic currents (mIPSCs) in the Mecp2-mutant cortex reveals a reduction in mEPSC amplitudes, without significant change in the average mIPSC amplitude or frequency. These findings provide the first detailed electrophysiological analysis of Mecp2-mutant mice and provide a framework for understanding the pathophysiology of the disease and tools for studying the underlying disease mechanisms.}, Author = {Dani, Vardhan S. and Chang, Qiang and Maffei, Arianna and Turrigiano, Gina G. and Jaenisch, Rudolf and Nelson, Sacha B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Mice, Inbred BALB C;Chromosomal Proteins, Non-Histone;Electrophysiology;Animals;DNA-Binding Proteins;Humans;Mice, Mutant Strains;Synaptic Transmission;Methyl-CpG-Binding Protein 2;Female;Mutation;in vitro ;Patch-Clamp Techniques;Pyramidal Cells;Mice, Inbred C57BL;Disease Models, Animal;Male;research support, non-u.s. gov't ;Cerebral Cortex;21 Neurophysiology;Mice;24 Pubmed search results 2008;Repressor Proteins;Rett Syndrome}, Month = {8}, Nlm_Id = {7505876}, Number = {35}, Organization = {Department of Biology and Volen Center for Complex Systems, Brandeis University, MS 008, Waltham, MA 02454-9110, USA.}, Pages = {12560-5}, Pii = {0506071102}, Pubmed = {16116096}, Title = {Reduced cortical activity due to a shift in the balance between excitation and inhibition in a mouse model of Rett syndrome}, Uuid = {2C45B220-14C8-44DE-ACC1-88E4FF80893A}, Volume = {102}, Year = {2005}, url = {papers/Dani_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0506071102}} @article{Darbinian-Sarkissian:2006, Abstract = {Transcription of the HIV-1 genome is controlled by the cooperation of viral regulatory proteins and several host factors which bind to specific DNA sequences within the viral promoter spanning the long terminal repeat, (LTR). Here, we describe the identification of a novel protein, p27(SJ), present in a laboratory callus culture of Hypericum perforatum (St John's Wort) that suppresses transcription of the HIV-1 genome in several human cell types including primary culture of microglia and astrocytes. p27(SJ) associates with C/EBPbeta, a transcription factor that regulates expression of the HIV-1 genome in macrophages and monocytic cells, and the viral transactivator, Tat. The association of p27(SJ) with C/EBPbeta and Tat alters their subcellular localization, causing their accumulation in the perinuclear cytoplasmic compartment of the cells. Fusion of a nuclear localization signal to p27(SJ) forces its entry into the nucleus and diminishes the capacity of p27(SJ) to suppress Tat activity, but does not alter its ability to suppress C/EBPbeta activation of the LTR. Results from binding assays showed the inhibitory effect of p27(SJ) on C/EBPbeta interaction with DNA. Finally, our results demonstrate that expression of p27(SJ) decreases the level of viral replication in HIV-1-infected cells. These observations suggest the potential for the development of a therapeutic advance based on p27(SJ) protein to control HIV-1 transcription and replication in cells associated with HIV-1 infection in the brain.}, Author = {Darbinian-Sarkissian, N. and Darbinyan, A. and Otte, J. and Radhakrishnan, S. and Sawaya, B. E. and Arzumanyan, A. and Chipitsyna, G. and Popov, Y. and Rappaport, J. and Amini, S. and Khalili, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Phytotherapy;Gene Expression Regulation, Viral;HIV-1;Astrocytes;Base Sequence;U937 Cells;Transfection;Cells, Cultured;Humans;Microglia;Plant Proteins;Hypericum;Depression, Chemical;11 Glia;HIV Infections;Gene Therapy;Genome, Viral;Virus Replication;Research Support, N.I.H., Extramural;Terminal Repeat Sequences;Molecular Sequence Data}, Month = {2}, Nlm_Id = {9421525}, Number = {4}, Organization = {Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA, USA.}, Pages = {288-95}, Pii = {3302649}, Pubmed = {16251997}, Title = {p27(SJ), a novel protein in St John's Wort, that suppresses expression of HIV-1 genome}, Uuid = {2F05D204-EA51-4D43-92A8-A678BC28D40F}, Volume = {13}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3302649}} @article{Das:2003, Abstract = {Two-photon excitation microscopy was used to reconstruct cell divisions in living zebrafish embryonic retinas. Contrary to proposed models for vertebrate asymmetric divisions, no apico-basal cell divisions take place in the zebrafish retina during the generation of postmitotic neurons. However, a surprising shift in the orientation of cell division from central-peripheral to circumferential occurs within the plane of the ventricular surface. In the sonic you (syu) and lakritz (lak) mutants, the shift from central-peripheral to circumferential divisions is absent or delayed, correlating with the delay in neuronal differentiation and neurogenesis in these mutants. The reconstructions here show that mitotic cells always remain in contact with the opposite basal surface by means of a thin basal process that can be inherited asymmetrically. 22487150 0896-6273 Journal Article}, Author = {Das, T. and Payer, B. and Cayouette, M. and Harris, W. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Neuron}, Keywords = {Recombinant Fusion Proteins/genetics;Mutation;Zebrafish;10 Development;Cell Division/physiology;Rats;Time Factors;Retina/*cytology/*embryology;Fluorescent Dyes;Luminescent Proteins/genetics;Microscopy, Video;F;Mitosis;Animal;Support, Non-U.S. Gov't;Neurons/*cytology;Stem Cells/cytology}, Number = {4}, Organization = {Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom.}, Pages = {597-609}, Pubmed = {12597858}, Title = {In vivo time-lapse imaging of cell divisions during neurogenesis in the developing zebrafish retina}, Uuid = {823894E7-231B-4479-B765-8BC9CDAAA145}, Volume = {37}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12597858}} @article{Dasgupta:2005, Abstract = {Females are more susceptible than males to multiple sclerosis (MS). However, the underlying mechanism behind this gender difference is poorly understood. Because the presence of neuroantigen-primed T cells within the CNS is necessary for the development of MS, the present study was undertaken to investigate the activation of microglia by myelin basic protein (MBP)-primed T cells of male, female and castrated male mice. Interestingly, MBP-primed T cells isolated from female and castrated male but not from male mice induced the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokines (IL-1b, IL-1a, IL-6 and TNF-a) in microglia by cell-cell contact. Again there was no apparent defect in male microglia because MBP-primed T cells isolated from female and castrated male but not male mice were capable of inducing the production of NO in male primary microglia. Inhibition of female T cell contact-mediated microglial expression of proinflammatory molecules by dominant-negative mutants of p65 and C/EBPb suggest that female MBP-primed T cells induce microglial expression of proinflammatory molecules through the activation of NF-kB and C/EBPb. Interestingly, MBP-primed T cells of male, female and castrated male mice were able to induce microglial activation of NF-kB. However, MBP-primed T cells of female and castrated male but not male mice induced microglial activation of C/EBPb. These studies suggest that microglial activation of C/EBPb but not NF-kB by T cell:microglial contact is a gender-specific event and that male MBP-primed T cells are not capable of inducing microglial expression of proinflammatory molecules due to their inability to induce the activation of C/EBPb in microglia. This novel gender-sensitive activation of microglia by neuroantigen-primed T cell contact could be one of the mechanisms behind the female-loving nature of MS.}, Author = {Dasgupta, and Jana, and Liu, and Pahan,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {Castration;Research Support, N.I.H., Extramural;NF-kappa B;Male;Animals;Transcription, Genetic;Research Support, U.S. Gov't, P.H.S.;Myelin Basic Proteins;Central Nervous System;CCAAT-Enhancer-Binding Protein-beta;Interleukin-1;T-Lymphocytes;11 Glia;Mutation;Multiple Sclerosis;Tumor Necrosis Factor-alpha;Cell Membrane;Nitric Oxide;Oligonucleotide Array Sequence Analysis;Female;Sex Factors;Microglia;Cell Nucleus;Interleukin-6;Mice;Inflammation;Research Support, Non-U.S. Gov't;RNA;Genes, Dominant;Cytokines;Immunoblotting}, Month = {7}, Nlm_Id = {2985121R}, Number = {38}, Organization = {Section of Neuroscience, Oral Biology, University of Nebraska Medical Center, Lincoln, NE 68583-0740.}, Pages = {32609-17}, Pii = {M500299200}, Pubmed = {16046404}, Title = {Myelin basic protein-primed T cells of female but not male mice induce nitric oxide synthase and proinflammatory cytokines in microglia: Implications for gender bias in multiple sclerosis}, Uuid = {9B3B99B6-9F0F-11DA-8D49-000D9346EC2A}, Volume = {280}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1074/jbc.M500299200}} @article{Daval:2004, Abstract = {Continuous generation of new neurons has been demonstrated in the adult mammalian brain, and this process was shown to be stimulated by various pathologic conditions, including cerebral ischemia. Because brain oxygen deprivation is particularly frequent in neonates and represents the primary event of asphyxia, we analyzed long-term consequences of transient hypoxia in the newborn rat. Within 24 h after birth, animals were exposed to 100\%N2 for 20 min at 36 degrees C, and temporal changes in the vulnerable CA1 hippocampus were monitored. Cell density measurements revealed delayed cell death in the pyramidal cell layer reflecting apoptosis, as shown by characteristic nuclear morphology and expression levels of Bcl-2, Bax, and caspase-3. Neuronal loss was confirmed by reduced density of neuron-specific enolase (NSE)-labeled cells, and peaked by 1 wk post insult, to reach 27\%of total cells. A gradual recovery then occurred, and no significant difference in cell density could be detected between controls and hypoxic rats at postnatal d 21. Repeated injections of bromodeoxyuridine (50 mg/kg) showed that newly divided cells expressing neuronal markers increased by 225\%in the germinative subventricular zone, and they tended to migrate along the posterior periventricle toward the hippocampus. Therefore, transient hypoxia in the newborn rat triggered apoptosis in the CA1 hippocampus followed by increased neurogenesis and apparent anatomical recovery, suggesting that the developing brain may have a high capacity for self-repair. 0031-3998 Journal article}, Author = {Daval, J. L. and Pourie, G. and Grojean, S. and Lievre, V. and Strazielle, C. and Blaise, S. and Vert, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {Pediatr Res}, Keywords = {06 Adult neurogenesis injury induced;D pdf}, Organization = {INSERM EMI 0014, Faculte de Medecine, UHP, 54500 Vandoeuvre-les-Nancy, France, and Medecine et Reanimation Neonatales, Maternite Regionale, 54000 Nancy, France.}, Title = {Neonatal Hypoxia Triggers Transient Apoptosis Followed by Neurogenesis in the Rat CA1 Hippocampus}, Uuid = {66B9D124-96A0-48AA-A35C-608EC802180A}, Year = {2004}, url = {papers/Daval_PediatrRes2004.pdf}} @article{Davalos:2005, Abstract = {Parenchymal microglia are the principal immune cells of the brain. Time-lapse two-photon imaging of GFP-labeled microglia demonstrates that the fine termini of microglial processes are highly dynamic in the intact mouse cortex. Upon traumatic brain injury, microglial processes rapidly and autonomously converge on the site of injury without cell body movement, establishing a potential barrier between the healthy and injured tissue. This rapid chemotactic response can be mimicked by local injection of ATP and can be inhibited by the ATP-hydrolyzing enzyme apyrase or by blockers of G protein-coupled purinergic receptors and connexin channels, which are highly expressed in astrocytes. The baseline motility of microglial processes is also reduced significantly in the presence of apyrase and connexin channel inhibitors. Thus, extracellular ATP regulates microglial branch dynamics in the intact brain, and its release from the damaged tissue and surrounding astrocytes mediates a rapid microglial response towards injury.}, Author = {Davalos, Dimitrios and Grutzendler, Jaime and Yang, Guang and Kim, Jiyun V. and Zuo, Yi and Jung, Steffen and Littman, Dan R. and Dustin, Michael L. and Gan, Wen-Biao B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Signal Transduction;Animals;Astrocytes;Phagocytosis;Brain;Microglia;Chemotaxis;Cell Communication;Mice, Transgenic;Reaction Time;Connexins;11 Glia;Green Fluorescent Proteins;Adenosine Triphosphate;Brain Injuries;Research Support, U.S. Gov't, P.H.S.;Apyrase;Gliosis;Mice;Research Support, N.I.H., Extramural;Receptors, Purinergic P2;Research Support, Non-U.S. Gov't}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {Molecular Neurobiology Program, Department of Physiology and Neuroscience, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.}, Pages = {752-8}, Pii = {nn1472}, Pubmed = {15895084}, Title = {ATP mediates rapid microglial response to local brain injury in vivo}, Uuid = {3E2D7CA0-FFAF-11DA-9E68-000D9346EC2A}, Volume = {8}, Year = {2005}, url = {papers/Davalos_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1472}} @article{Davidoff:2001, Abstract = {Inhibition of tumor-induced neovascularization appears to be an effective anticancer approach, although long-term angiogenesis inhibition may be required. An alternative to chronic drug administration is a gene therapy-mediated approach in which long-term in vivo protein expression is established. We have tested this approach by modifying murine bone marrow-derived cells with a gene encoding an angiogenesis inhibitor: a soluble, truncated form of the vascular endothelial growth factor receptor-2, fetal liver kinase-1 (Flk-1). Murine bone marrow cells were transduced with a retroviral vector encoding either truncated, soluble Flk-1 (tsFlk-1) together with green fluorescent protein (GFP) or GFP alone. Tumor growth in mice challenged 3 months after transplantation with tsFlk-1-expressing bone marrow cells was significantly inhibited when compared with tumor growth in control-transplanted mice. Immunohistochemical analysis of tumors in each group demonstrated colocalization of GFP expression in cells staining with endothelial cell markers, suggesting that the endothelial cells of the tumor-induced neovasculature were derived, at least in part, from bone marrow precursors. These results suggest that long-term expression of a functional angiogenesis inhibitor can be generated through gene-modified, bone marrow-derived stem cells, and that this approach can have significant anticancer efficacy. Modifying these cells seems to have the added potential benefit of targeting transgene expression to the tumor neovasculature, because bone marrow-derived endothelial cell precursors seem to be recruited in the process of tumor-induced angiogenesis.}, Author = {Davidoff, A. M. and Ng, C. Y. and Brown, P. and Leary, M. A. and Spurbeck, W. W. and Zhou, J. and Horwitz, E. and Vanin, E. F. and Nienhuis, A. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {1078-0432}, Journal = {Clin Cancer Res}, Keywords = {Receptors, Growth Factor;Angiogenesis Inhibitors;Gene Expression Regulation;Animals;Fluorescent Antibody Technique;Transfection;Humans;Female;Mice, SCID;11 Glia;Green Fluorescent Proteins;Xenograft Model Antitumor Assays;Genetic Vectors;Hematopoietic Stem Cell Transplantation;Neovascularization, Pathologic;Mice, Inbred Strains;Bone Marrow Cells;Gene Therapy;Receptors, Vascular Endothelial Growth Factor;Tumor Cells, Cultured;Research Support, U.S. Gov't, P.H.S.;Receptor Protein-Tyrosine Kinases;Mice;Cell Division;Luminescent Proteins;Neoplasms, Experimental;Research Support, Non-U.S. Gov't}, Medline = {21439142}, Month = {9}, Nlm_Id = {9502500}, Number = {9}, Organization = {Department of Surgery, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA. andrew.davidoff\@stjude.org}, Pages = {2870-9}, Pubmed = {11555605}, Title = {Bone marrow-derived cells contribute to tumor neovasculature and, when modified to express an angiogenesis inhibitor, can restrict tumor growth in mice}, Uuid = {9B91A181-0D94-454C-8CE9-136E4447B9FC}, Volume = {7}, Year = {2001}} @article{Davidson:2007, Abstract = {RNA interference (RNAi), a mediator of gene silencing, has swiftly become one of the most exciting and applicable biological discoveries. There has been rapid progress in identifying RNAi pathway components and elucidating the mechanisms of microRNA (miRNA) biogenesis and gene suppression. As a result, RNAi technologies have been successfully employed in a variety of systems as biological tools, and studies are underway to test the therapeutic utility of RNAi. In the span of several years, significant advances in the delivery of inhibitory RNAs in the nervous system have been made. We have glimpses into how endogenous miRNAs interface with neuronal development and function; in addition, RNAi has shown therapeutic efficacy in several mouse models of human neurological conditions. In this review, we summarize the current state-of-the-art of RNAi and its utility to neuroscientists.}, Author = {Davidson, Beverly L. and Boudreau, Ryan L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-13 09:45:17 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Models, Biological;24 Pubmed search results 2008;research support, non-u.s. gov't;Nervous System Physiology;RNA Interference;research support, n.i.h., extramural;Gene Therapy;Animals;Humans;Nervous System Diseases;review;RNA, Small Interfering; microRNAs; development}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Internal Medicine, University of Iowa, Iowa City, IA 52242, USA. beverly-davidson\@uiowa.edu}, Pages = {781-8}, Pii = {S0896-6273(07)00140-7}, Pubmed = {17359914}, Title = {RNA interference: a tool for querying nervous system function and an emerging therapy}, Uuid = {CD2A927F-B4B2-497B-99A4-18E233194F3A}, Volume = {53}, Year = {2007}, url = {papers/Davidson_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.02.020}} @article{Davy:2005, Abstract = {Eph receptors and ephrins have captured the interest of the developmental biology community in recent years for their pleiotropic functions during embryogenesis. Loss-of-function studies using various animal models have demonstrated the involvement of Ephs and ephrins in many aspects of embryogenesis including segmentation, neural crest cells migration, angiogenesis, and axon guidance. An essential property of this signaling pathway is the ability of both Ephs and ephrins to behave as receptors or ligands and their consequent cell autonomous and nonautonomous mode of action. While many reports did not discriminate between Eph autonomous signaling (forward) and ephrin autonomous signaling (reverse), recent genetic and in vivo studies have shown that both forward and reverse signaling play important roles during embryogenesis.}, Author = {Davy, Alice and Soriano, Philippe}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1058-8388}, Journal = {Dev Dyn}, Keywords = {10 Development;Signal Transduction;Animals;Xenopus;Humans;Ephrins;Neural Crest;review;Receptors, Eph Family;Models, Biological;Cell Movement;Axons;research support, non-u.s. gov't;10 circuit formation;Neovascularization, Physiologic;research support, u.s. gov't, p.h.s.;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Ligands}, Month = {1}, Nlm_Id = {9201927}, Number = {1}, Organization = {Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.}, Pages = {1-10}, Pubmed = {15580616}, Title = {Ephrin signaling in vivo: look both ways}, Uuid = {F497D3B7-A87F-4D82-9ABC-5D3F0169C242}, Volume = {232}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dvdy.20200}} @article{Daw:2007, Abstract = {Feedforward inhibitory GABAergic transmission is critical for mature cortical circuit function; in the neonate, however, GABA is depolarizing and believed to have a different role. Here we show that the GABAA receptor-mediated conductance is depolarizing in excitatory (stellate) cells in neonatal (postnatal day [P]3-5) layer IV barrel cortex, but GABAergic transmission at this age is not engaged by thalamocortical input in the feedforward circuit and has no detectable circuit function. However, recruitment occurs at P6-7 as a result of coordinated increases in thalamic drive to fast-spiking interneurons, fast-spiking interneuron-stellate cell connectivity and hyperpolarization of the GABAA receptor-mediated response. Thus, GABAergic circuits are not engaged by thalamocortical input in the neonate, but are poised for a remarkably coordinated development of feedforward inhibition at the end of the first postnatal week, which has profound effects on circuit function at this critical time in development.}, Author = {Daw, Michael I. and Ashby, Michael C. and Isaac, John T. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;21 Activity-development;research support, n.i.h., intramural;21 Circuit structure-function;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, UK.}, Pages = {453-61}, Pii = {nn1866}, Pubmed = {17351636}, Title = {Coordinated developmental recruitment of latent fast spiking interneurons in layer IV barrel cortex}, Uuid = {9DB275A5-4BC8-4F0D-9DF8-CF94F679EA56}, Volume = {10}, Year = {2007}, url = {papers/Daw_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1866}} @article{Dawson:2003a, Abstract = {Glial progenitor cells of the developing CNS committed to the oligodendrocyte lineage (OPCs) express the chondroitin sulfate proteoglycan, NG2. A proportion of OPCs fail to differentiate past the stage at which they express NG2 and the lipid antigen O4 and persist in the adult CNS in a phenotypically immature form. However, the physiological function of NG2(+) cells in the adult CNS is unknown. Using antibodies against NG2 we show that NG2 is expressed by a distinct cell population in the mature CNS with the homogeneous antigenic phenotype of oligodendrocyte progenitors. The morphology of NG2(+) OPCs varies from region to region, reflecting the different structural environments, but they appear to represent a homogeneous population within any one gray or white matter region. A study of nine CNS regions showed that NG2(+) OPCs are numerous throughout the CNS and numbers in the white matter are only 1.5 times that in the gray. Whereas the ratio of OPCs to myelinating oligodendrocytes in the spinal cord gray and white matter approximates 1:4, gray matter regions of the forebrain have a 1:1 ratio, a phenomenon that will have consequences for oligodendrocyte replacement following demyelination. BrdU incorporation experiments showed that NG2(+) cells are the major dividing cell population of the adult rat CNS. Since very little apoptosis was detected and BrdU became increasingly present in oligodendrocytes after a 10-day pulse chase, with a concomitant decrease in NG2(+) BrdU incorporating cells, we suggest that the size of the oligodendrocyte population may actually increase during adult life. 1044-7431 Journal Article}, Author = {Dawson, M. R. and Polito, A. and Levine, J. M. and Reynolds, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {Rats, Sprague-Dawley;Cell Cycle/physiology;Comparative Study;Central Nervous System/cytology/*metabolism;Antigens/*biosynthesis/genetics;Rats;Neuroglia/cytology/*metabolism;Proteoglycans/*biosynthesis/genetics;11 Glia;Stem Cells/cytology/*metabolism;Support, Non-U.S. Gov't;Animals;Male;G pdf;Gene Expression Regulation/physiology}, Number = {2}, Organization = {Department of Neuroinflammation, Imperial College London, Charing Cross Hospital Campus, UK.}, Pages = {476-88}, Pubmed = {14572468}, Title = {NG2-expressing glial progenitor cells: an abundant and widespread population of cycling cells in the adult rat CNS}, Uuid = {1C48BD05-8B72-4C7E-A5AF-57DF4A2F6EF0}, Volume = {24}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14572468}} @article{Dawson:2003, Abstract = {Parkinson's disease (PD) is a complex disorder with many different causes, yet they may intersect in common pathways, raising the possibility that neuroprotective agents may have broad applicability in the treatment of PD. Current evidence suggests that mitochondrial complex I inhibition may be the central cause of sporadic PD and that derangements in complex I cause alpha-synuclein aggregation, which contributes to the demise of dopamine neurons. Accumulation and aggregation of alpha-synuclein may further contribute to the death of dopamine neurons through impairments in protein handling and detoxification. Dysfunction of parkin (a ubiquitin E3 ligase) and DJ-1 could contribute to these deficits. Strategies aimed at restoring complex I activity, reducing oxidative stress and alpha-synuclein aggregation, and enhancing protein degradation may hold particular promise as powerful neuroprotective agents in the treatment of PD.}, Author = {Dawson, Ted M. and Dawson, Valina L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:45 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Human;Dopamine;Nerve Degeneration;Animals;review, tutorial;Brain;Mitochondria;review;Mutation;21 Neurodegenerative;Animals, Genetically Modified;Cysteine Endopeptidases;Parkinson Disease;Ubiquitin;Multienzyme Complexes;Support, Non-U.S. Gov't;Oxidative Stress;21 Neurophysiology;Neurons;Ubiquitin-Protein Ligases;Support, U.S. Gov't, P.H.S.;Parkinsonian Disorders;Nerve Tissue Proteins;Electron Transport Complex I}, Medline = {22954844}, Month = {10}, Nlm_Id = {0404511}, Number = {5646}, Organization = {Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. tdawson\@jhmi.edu}, Pages = {819-22}, Pii = {302/5646/819}, Pubmed = {14593166}, Title = {Molecular pathways of neurodegeneration in Parkinson's disease}, Uuid = {BA7EF0AB-446A-4D65-ADA7-0DBAA6258E6E}, Volume = {302}, Year = {2003}, url = {papers/Dawson_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1087753}} @article{Dayer:2005, Abstract = {Ongoing neurogenesis in the adult mammalian dentate gyrus and olfactory bulb is generally accepted, but its existence in other adult brain regions is highly controversial. We labeled newly born cells in adult rats with the S-phase marker bromodeoxyuridine (BrdU) and used neuronal markers to characterize new cells at different time points after cell division. In the neocortex and striatum, we found BrdU-labeled cells that expressed each of the eight neuronal markers. Their size as well as staining for gamma-aminobutyric acid (GABA), glutamic acid decarboxylase 67, calretinin and/or calbindin, suggest that new neurons in both regions are GABAergic interneurons. BrdU and doublecortin-immunoreactive (BrdU+/DCX+) cells were seen within the striatum, suggesting migration of immature neurons from the subventricular zone. Surprisingly, no DCX+ cells were found within the neocortex. NG2 immunoreactivity in some new neocortical neurons suggested that they may instead be generated from the NG2+ precursors that reside within the cortex itself.}, Author = {Dayer, Alexandre G. and Cleaver, Kathryn M. and Abouantoun, Thamara and Cameron, Heather A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {01 Adult neurogenesis general}, Month = {1}, Nlm_Id = {0375356}, Number = {3}, Organization = {Unit on Neuroplasticity, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892.}, Pages = {415-27}, Pii = {jcb.200407053}, Pubmed = {15684031}, Title = {New GABAergic interneurons in the adult neocortex and striatum are generated from different precursors}, Uuid = {09F42FC2-CE44-11D9-B244-000D9346EC2A}, Volume = {168}, Year = {2005}, url = {papers/Dayer_JCellBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200407053}} @article{DeFazio:2000, Abstract = {Recent studies have demonstrated an important role for the N-methyl-D-aspartate receptor (NMDAR) in epilepsy. NMDARs have also been shown to play a critical role in hyperexcitability associated with several animal models of human epilepsy. Using whole-cell voltage clamp recordings in brain slices, we studied evoked paroxysmal discharges in the freeze-lesion model of neocortical microgyria. The voltage dependence of epileptiform discharges indicated that these paroxysmal events were produced by a complex pattern of excitatory and inhibitory inputs. We examined the effect of the NMDAR antagonist D-2-amino-5-phosphopentanoic acid (APV) and the NMDA receptor subunit type 2B (NR2B)-selective antagonist ifenprodil on the threshold, peak amplitude, and area of evoked epileptiform discharges in brain slices from lesioned animals. Both compounds consistently raised the threshold for evoking the discharge but had modest effects on the discharge peak and amplitude. For comparison with nonlesioned cortex, we examined the effects of ifenprodil on the epileptiform discharge evoked in the presence of 2 microM bicuculline (partial disinhibition). In slices from nonlesioned cortex, 10 microM ifenprodil had little effect on the threshold whereas 71\%of the recordings in bicuculline-treated lesioned cortex showed a >25\%increase in threshold. These results suggest that NR2B-containing receptors are functionally enhanced in freeze-lesioned cortex and may contribute to the abnormal hyperexcitability observed in this model of neocortical microgyria.}, Author = {DeFazio, R. A. and Hablitz, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Excitatory Amino Acid Antagonists;Pregnancy;Piperidines;Animals;In Vitro;Evoked Potentials;Rats;Humans;Brain;21 Epilepsy;Female;Epilepsy;Rats, Sprague-Dawley;2-Amino-5-phosphonovalerate;Pyramidal Cells;Patch-Clamp Techniques;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Research Support, Non-U.S. Gov't}, Medline = {20102988}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.}, Pages = {315-21}, Pubmed = {10634874}, Title = {Alterations in NMDA receptors in a rat model of cortical dysplasia}, Uuid = {33B5F443-E433-4FA8-9DFF-36CADF518E15}, Volume = {83}, Year = {2000}} @article{DeKosky:2003, Abstract = {Early detection of neurodegenerative disorders would provide clues to the underlying pathobiology of these diseases and would enable more effective diagnosis and treatment of patients. Recent advances in molecular neuroscience have begun to provide the tools to detect diseases like Alzheimer's disease, Parkinson's disease, and others early in their course and potentially even before the development of clinical manifestations of disease. These genetic, imaging, clinical, and biochemical tools are being validated in a number of studies. Early detection of these slowly progressive diseases offers the promise of presymptomatic diagnosis and, ultimately, of disease-modifying medications for use early in disease and during the presymptomatic period.}, Author = {DeKosky, Steven T. and Marek, Kenneth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:45 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Human;Dopamine;Aging;Memory;review, tutorial;Brain;Diagnostic Imaging;review;Mutation;21 Neurodegenerative;Parkinson Disease;Time Factors;Genetic Predisposition to Disease;Support, Non-U.S. Gov't;Alzheimer Disease;21 Neurophysiology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Huntington Disease;Neurodegenerative Diseases;Biological Markers;Cognition Disorders;Genetic Markers}, Medline = {22954847}, Month = {10}, Nlm_Id = {0404511}, Number = {5646}, Organization = {Department of Neurology and Alzheimer Disease Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. DeKoskyST\@upmc.edu}, Pages = {830-4}, Pii = {302/5646/830}, Pubmed = {14593169}, Title = {Looking backward to move forward: early detection of neurodegenerative disorders}, Uuid = {E4C1673C-8A27-429C-841D-B89E2B0FF1B4}, Volume = {302}, Year = {2003}, url = {papers/DeKosky_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1090349}} @article{De-Marchis:2001, Abstract = {Continual neurogenesis in the subventricular zone (SVZ) of postnatal and adult mammalian forebrain has been well documented, but the mechanisms underlying cell migration and differentiation in this region are poorly understood. We have developed novel in vivo and in vitro methods to investigate these processes. Using stereotaxic injections of a variety of tracers/tracker [Cholera Toxin beta subunit (CTb-), Fluorogold (FG), and Cell Tracker Green (CTG)], we could efficiently label SVZ cells. Over several days, labeled cells migrate along the rostral migratory stream (RMS) to their final differentiation site in the olfactory bulb (OB). The compatibility of these tracers/trackers with immunohistochemistry allows for cell labeling with multiple dyes (e.g., CTb and CTG) and/or specific cell antigens. To investigate the dynamics of migration we labeled SVZ progenitor cells with small injections of CTG and monitored the movements of individual cells in fresh parasagittal brain slices over several hours using time-lapse confocal microscopy. Our observations suggest that tangential cell migration along the RMS occurs more rapidly than radial cell migration into the OB granule cell layer. To investigate migration over longer time periods, we developed an in vitro organotypic slice in which labeled SVZ progenitors migrate along the RMS and differentiate within the OB. The phenotypic characteristics of these cells in vitro were equivalent to those observed in vivo. Taken together, these methods provide useful tools investigating cell migration and differentiation in a preparation that maintains the anatomical organization of the RMS. 0022-3034 Journal Article}, Author = {De Marchis, S. and Fasolo, A. and Shipley, M. and Puche, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {J Neurobiol}, Keywords = {Fluorescent Dyes;Neurons/*physiology;B both;Animals;Stereotaxic Techniques;Dextrans;Microscopy, Confocal;02 Adult neurogenesis migration;*Stilbamidines;Stem Cells/*physiology;Olfactory Bulb/cytology/*physiology;Animals, Newborn;Prosencephalon/cytology/*physiology;Support, Non-U.S. Gov't;Biotin/*analogs &derivatives;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Mice;Cell Differentiation/physiology;Immunohistochemistry;Organ Culture}, Number = {4}, Organization = {Department of Human and Animal Biology, University of Torino, 10123 Torino, Italy.}, Pages = {326-38}, Title = {Unique neuronal tracers show migration and differentiation of SVZ progenitors in organotypic slices}, Uuid = {3324AFE4-DD35-4E07-A1BA-67889EB89C7B}, Volume = {49}, Year = {2001}, url = {papers/DeMarchis_JNeurobiol2001}} @article{De-Palma:2003, Abstract = {Angiogenic tumor vessels are promising targets for the activity and the selective delivery of cancer therapeutics. The bone marrow contributes different cell types to the tumor stroma, including hematopoietic cells and, as recently suggested, vascular endothelial cells (ECs). Thus, transplantation of genetically modified bone marrow progenitors may represent a vehicle for the transport of gene therapy to tumors. We transduced bone marrow progenitors with lentiviral vectors expressing genes from transcription-regulatory elements of Tie2/Tek gene. When tumors were grown in the transplanted mice, the new vector marked a distinct hematopoietic population that 'homed' to the tumor and closely interacted with vascular ECs at the tumor periphery. These Tie2-expressing mononuclear (TEM) cells had a distinguishable phenotype and were present selectively at angiogenic sites. Unexpectedly, we did not find bone marrow-derived ECs in tumor vessels when we transplanted bone marrow progenitors constitutively expressing a marker gene from the Tie2 or ubiquitously active promoters. By delivering a 'suicide' gene, we selectively eliminated the TEM cells and achieved substantial inhibition of angiogenesis and slower tumor growth without systemic toxicity. Thus, TEM cells may account for the proangiogenic activity of bone marrow-derived cells in tumors, may represent a new target for drug development and may provide the means for selective gene delivery and targeted inhibition of tumor angiogenesis.}, Author = {De Palma, Michele and Venneri, Mary Anna and Roca, Cristina and Naldini, Luigi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {Transduction, Genetic;Gene Targeting;Animals;Humans;Bone Marrow Transplantation;Phenotype;Receptor, TIE-2;Female;11 Glia;Male;Mice, Nude;Hematopoietic Stem Cell Transplantation;Neovascularization, Pathologic;Mice, Inbred Strains;Genetic Vectors;Gene Therapy;Tumor Cells, Cultured;Receptor Protein-Tyrosine Kinases;Mice;Genes, Reporter;Biological Markers;Neoplasms, Experimental;Hematopoietic Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {22662628}, Month = {6}, Nlm_Id = {9502015}, Number = {6}, Organization = {Laboratory for Gene Transfer and Therapy, IRCC, Institute for Cancer Research and Treatment, University of Torino Medical School, Strada Provinciale 142, 10060 Candiolo, Torino, Italy.}, Pages = {789-95}, Pii = {nm871}, Pubmed = {12740570}, Title = {Targeting exogenous genes to tumor angiogenesis by transplantation of genetically modified hematopoietic stem cells}, Uuid = {F530D3BE-FD2C-477F-8C5A-1025F3D97FD8}, Volume = {9}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm871}} @article{De-Paola:2006, Abstract = {We imaged axons in layer (L) 1 of the mouse barrel cortex in vivo. Axons from thalamus and L2/3/5, or L6 pyramidal cells were identified based on their distinct morphologies. Their branching patterns and sizes were stable over times of months. However, axonal branches and boutons displayed cell type-specific rearrangements. Structural plasticity in thalamocortical afferents was mostly due to elongation and retraction of branches (range, 1-150 microm over 4 days; approximately 5\%of total axonal length), while the majority of boutons persisted for up to 9 months (persistence over 1 month approximately 85\%). In contrast, L6 axon terminaux boutons were highly plastic (persistence over 1 month approximately 40 \%), and other intracortical axon boutons showed intermediate levels of plasticity. Retrospective electron microscopy revealed that new boutons make synapses. Our data suggest that structural plasticity of axonal branches and boutons contributes to the remodeling of specific functional circuits.}, Author = {De Paola, Vincenzo and Holtmaat, Anthony and Knott, Graham and Song, Sen and Wilbrecht, Linda and Caroni, Pico and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {plasticity;structural remodeling;Structure-Activity Relationship;imaging;in vivo;Optics;microscopy;Multiphoton;neocortex;axons;Synapses}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.}, Pages = {861-75}, Pii = {S0896-6273(06)00134-6}, Pubmed = {16543134}, Title = {Cell type-specific structural plasticity of axonal branches and boutons in the adult neocortex}, Uuid = {72A25FBA-1DF2-4B0A-859D-8E3731DF2C7F}, Volume = {49}, Year = {2006}, url = {papers/DePaola_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.02.017}} @article{De-Simone:2004, Abstract = {In the central nervous system (CNS), apoptosis plays an important role during development and is a primary pathogenic mechanism in several adult neurodegenerative diseases. A main feature of apoptotic cell death is the efficient and fast removal of dying cells by macrophages and nonprofessional phagocytes, without eliciting inflammation in the surrounding tissue. Apoptotic cells undergo several membrane changes, including the externalization of so-called "eat me" signals whose cognate receptors are present on professional phagocytes. Among these signals, the aminophospholipid phosphatidylserine (PS) appears to have a crucial and unique role in preventing the classical pro-inflammatory activation of macrophages, thus ensuring the silent and safe removal of apoptotic cells. Although extensively studied in the peripheral organs, the process of recognition and removal of apoptotic cells in the brain has only recently begun to be unraveled. Here, we summarize the evidence suggesting that upon interaction with PS-expressing apoptotic neurons, microglia may no longer promote the inflammatory cascade, but rather facilitate the elimination of damaged neurons through antiinflammatory and neuroprotective functions. We propose that the anti-inflammatory microglial phenotype induced through the activation of the specific PS receptor (PtdSerR), expressed by resting and activated microglial cells, could be relevant to the final outcome of neurodegenerative diseases, in which apoptosis seems to play a crucial role.}, Author = {De Simone, Roberta and Ajmone-Cat, Maria Antonietta and Minghetti, Luisa}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0893-7648}, Journal = {Mol Neurobiol}, Keywords = {Alpha;Human;Inflammation;Apoptosis;Not relevant;11 Glia;Microglia;review, tutorial;Support, Non-U.S. Gov't;Animals;review;Neurons}, Month = {4}, Nlm_Id = {8900963}, Number = {2}, Organization = {Department of Cell Biology and Neurosciences, Istituto Superiore di Sanit\`{a}, Viale Regina Elena 299, 00161 Italy.}, Pages = {197-212}, Pii = {MN:29:2:197}, Pubmed = {15126686}, Title = {Atypical antiinflammatory activation of microglia induced by apoptotic neurons: possible role of phosphatidylserine-phosphatidylserine receptor interaction}, Uuid = {4BEEB42C-8AF9-4DF5-AC9E-6A98906FD8A7}, Volume = {29}, Year = {2004}} @article{Deacon:1994, Abstract = {In order to determine whether the lateral ganglionic eminence (LGE) of the fetal telencephalon is the primary source of striatal precursors in striatal transplants and tissue cultures, cells derived exclusively from the LGE of fetal rat brains were transplanted into the quinolinic-acid-lesioned striatum of adult rats. After 2-3 months they produced grafts that were almost entirely AChE-positive as well as DARPP-32-, TH-, and calbindin-immunoreactive. The grafts were integrated into the host striatum so that host corticofugal fiber tracts interdigitated with graft tissues similar to the way they penetrate the gray matter of the normal striatum. Fast Blue dye injected into the ipsilateral globus pallidus of LGE grafted produced retrogradely labeled neurons within the grafts, but Fluorogold dye injected into the ipsilateral substantia nigra did not. In a separate experiment using DARPP-32-immunohistochemstry as a striatal marker, fetal (E16) and neonatal (P2) rat brains showed DARPP-32 immunoreactivity in the LGE but not in the adjacent medial ganglionic eminence (MGE). In summary, both fetal LGE cells and LGE grafts express specific striatal markers, and LGE grafts integrate into the host striatum and innervate the major striatal efferent target within the host brain. These data suggest that the LGE is the origin of cells committed to striatal phenotypes in the developing brain. 0006-8993 Journal Article}, Author = {Deacon, T. W. and Pakzaban, P. and Isacson, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Brain Res}, Keywords = {Animals;Acetylcholinesterase/analysis;Efferent Pathways;Rats;Fluorescent Antibody Technique;*Fetal Tissue Transplantation;Tyrosine 3-Monooxygenase/analysis;Rats, Sprague-Dawley;Nerve Tissue Proteins/analysis;Male;*Phosphoproteins;N;Amidines;Support, Non-U.S. Gov't;19 Neocortical evolution;Calcium-Binding Protein, Vitamin D-Dependent/analysis;Telencephalon/*cytology/embryology/transplantation;Dopamine/analysis;Neostriatum/chemistry/*cytology/transplantation;Support, U.S. Gov't, P.H.S.;Immunohistochemistry}, Number = {1-2}, Organization = {Neuroregeneration Laboratory, McLean Hospital, Belmont, MA 02178, USA.}, Pages = {211-9}, Pubmed = {7704606}, Title = {The lateral ganglionic eminence is the origin of cells committed to striatal phenotypes: neural transplantation and developmental evidence}, Uuid = {7EE40E68-A56C-4FC8-A88A-7471EF4E819B}, Volume = {668}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7704606}} @article{Debassio:1985, Abstract = {Although there is extensive literature documenting the effects of undernutrition on brain development, most studies have been concerned with cell differentiation with little attention given to neuronal migration. In a rat model we have investigated the effect of chronic protein deprivation on cell migration from the anterior lateral ventricle to the olfactory bulb. By using standard autoradiographic techniques and comparing the position of heavily labeled cells within the migratory stream, we estimated the migration rate to be 100 microns/h in 25\%-casein-diet rats and between 33 and 70 microns/h in 8\%-casein-diet rats. We therefore conclude that migration is slowed in chronically protein-deprived rats and this slowed migration may be related to subsequent abnormalities of cell differentiation seen in protein-deprived rats. eng Journal Article}, Author = {Debassio, W. A. and Kemper, T. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Journal = {Brain Res}, Keywords = {Protein Deficiency/*embryology;Female;Rats;Animal;Caseins/administration &dosage;Pregnancy;Mitosis;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Cell Movement;Rats, Inbred Strains;C abstr;Olfactory Bulb/*embryology}, Number = {2}, Pages = {191-6.}, Title = {The effects of protein deprivation on neuronal migration in rats}, Uuid = {9352DEA3-22BA-4E05-BCEA-CEED4C301A58}, Volume = {352}, Year = {1985}} @article{Decherchi:2000, Abstract = {The present work investigates the extent to which mature central neurons acutely or chronically axotomized by a spinal lesion still maintained the potential to regenerate an axon following post-traumatic nerve grafting within supra-lesional spinal structures. In adult rats, a C3 cervical hemisection (injury) was made and an autologous segment of the peroneal nerve was implanted 2mm rostrally into the ventrolateral part of the ipsilateral C2 spinal cord. Nerve graft implantations were carried out acutely at the time of injury (group I, acute conditions) or chronically, three weeks post-injury (group II, chronic conditions). Central neurons axotomized by the spinal lesion were labeled by True Blue injected at the lesion site at the time of trauma. Central neurons regenerating axons within the nerve grafts were labeled with either horseradish peroxidase (only in group I, n=4) or Nuclear Yellow (group I, n=3 and group II, n=6) applied two to four months post-grafting to the distal cut end of the nerve grafts. Neurons with dual staining (True Blue/Nuclear Yellow) represented central regenerating neurons which were previously axotomized by the spinal lesion and which had retained the capacity for axonal regeneration for a delayed period after injury. In group I (acute injury conditions), all types of labeled cells were found to be scattered with a clear bimodal distribution within the spinal cord and the brainstem. No labeled cells were found within the motor cortex. There was no statistically significant difference between horseradish peroxidase and all cells containing Nuclear Yellow (Nuclear Yellow and True Blue/Nuclear Yellow). In group II (chronic injury conditions), Nuclear Yellow- and True Blue/Nuclear Yellow-labeled cells had a similar dual distribution to that of group I, but were found to be significantly less represented (P=0.019). These differences are discussed in terms of capacity for cell survival and axonal regrowth after acute and chronic injury. The main conclusion is based on the evidence of dual staining of central neurons in both groups, which demonstrates that brainstem and spinal neurons involved in acute and chronic axotomy after spinal C3 lesion can survive the trauma and still maintain the capacity to regenerate lesioned axons within nerve grafts inserted rostrally (C2 spinal cord) to the primary site of injury. Although exhibited to a lesser extent in chronic than in acute conditions, this capacity was found to occur for as long as three weeks post-injury.These results indicate that supra-lesional post-traumatic nerve grafts may constitute an efficient delayed strategy for inducing axonal regrowth of chronically axotomized adult central neurons. We suggest that surgical intervention, which is not always possible immediately after a spinal cord injury, may be satisfactorily carried out after an appropriate delay.}, Author = {Decherchi, P. and Gauthier, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Fluorescent Dyes;Animals;Cervical Vertebrae;Rats;Neural Pathways;Postoperative Complications;Recovery of Function;Peroneal Nerve;Female;Axons;Rats, Sprague-Dawley;Tissue Transplantation;Spinal Cord;Nerve Regeneration;Spinal Cord Injuries;Survival Rate;Axotomy;Horseradish Peroxidase;24 Pubmed search results 2008;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {20521983}, Nlm_Id = {7605074}, Number = {1}, Organization = {Laboratoire des D{\'e}terminants Physiologiques de l'Activit{\'e} Physique, Facult{\'e} des Sciences du Sport de Marseille-Luminy, Universit{\'e} de la M{\'e}diterran{\'e}e (Aix-Marseille II), Case courrier 910, 163, avenue de Luminy, 13288 Marseille Cedex 09, France.}, Pages = {197-210}, Pii = {S0306452200003432}, Pubmed = {11068148}, Title = {Regrowth of acute and chronic injured spinal pathways within supra-lesional post-traumatic nerve grafts}, Uuid = {FA676BA0-BC33-42E6-835A-2C0A91409872}, Volume = {101}, Year = {2000}} @article{Dedesma:2006, Abstract = {The identity and biology of stem cells and progenitors in the adult brain are of considerable interest, because these cells hold great promise for the development of novel therapies for damaged brain tissue in human diseases. This research field critically needs biological markers that specifically identify the resident precursors in the germinal zones of the adult central nervous system so that the discovery of regulatory influences for adult neurogenesis may be facilitated. In this study, by using a combination of in situ hybridization, bromodeoxyuridine incorporation, immunocolocalization, and ultrastructural studies, we show that in rodents Tctex-1, a cytoplasmic dynein light chain, is selectively enriched in almost all cycling progenitors and young neuronal progeny, but not in mature granular cells and astrocytes, in the subgranular zone of the adult dentate gyrus. Tctex-1 is also selectively abundant in cells closely resembling previously described immature progenitors and migrating neuroblasts at the subventricular zone of the lateral ventricle. Our results suggest that Tctex-1 serves as a novel marker for the identification of neural progenitors of the adult brain. J. Comp. Neurol. 496:773-786, 2006. (c) 2006 Wiley-Liss, Inc.}, Author = {Dedesma, Carlos and Chuang, Jen-Zen Z. and Alfinito, Peter D. and Sung, Ching-Hwa H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0406041}, Number = {6}, Organization = {Graduate Program in Neuroscience, Weill Medical College of Cornell University, New York, New York 10021.}, Pages = {773-86}, Pubmed = {16628620}, Title = {Dynein light chain Tctex-1 identifies neural progenitors in adult brain}, Uuid = {018A3A9E-A204-4074-B44F-DD4198EDFFDB}, Volume = {496}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20958}} @article{Deisseroth:2006, Abstract = {Emerging technologies from optics, genetics, and bioengineering are being combined for studies of intact neural circuits. The rapid progression of such interdisciplinary "optogenetic" approaches has expanded capabilities for optical imaging and genetic targeting of specific cell types. Here we explore key recent advances that unite optical and genetic approaches, focusing on promising techniques that either allow novel studies of neural dynamics and behavior or provide fresh perspectives on classic model systems.}, Author = {Deisseroth, Karl and Feng, Guoping and Majewska, Ania K. and Miesenb{\"o}ck, Gero and Ting, Alice and Schnitzer, Mark J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Optics;24 Pubmed search results 2008;23 Technique;research support, n.i.h., extramural ;21 Neurophysiology;research support, non-u.s. gov't ;Neural Pathways;21 Calcium imaging;research support, u.s. gov't, non-p.h.s. ;Gene Targeting;Microscopy, Fluorescence;Animals;Brain;Humans;review;Nerve Net}, Month = {10}, Nlm_Id = {8102140}, Number = {41}, Organization = {Department of Bioengineering, Stanford University, Stanford, California 94305, USA. deissero\@stanford.edu}, Pages = {10380-6}, Pii = {26/41/10380}, Pubmed = {17035522}, Title = {Next-generation optical technologies for illuminating genetically targeted brain circuits}, Uuid = {ACB2BE32-5F98-43E9-B39D-19217939DB03}, Volume = {26}, Year = {2006}, url = {papers/Deisseroth_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3863-06.2006}} @article{Deisseroth:2004, Abstract = {A wide variety of in vivo manipulations influence neurogenesis in the adult hippocampus. It is not known, however, if adult neural stem/progenitor cells (NPCs) can intrinsically sense excitatory neural activity and thereby implement a direct coupling between excitation and neurogenesis. Moreover, the theoretical significance of activity-dependent neurogenesis in hippocampal-type memory processing networks has not been explored. Here we demonstrate that excitatory stimuli act directly on adult hippocampal NPCs to favor neuron production. The excitation is sensed via Ca(v)1.2/1.3 (L-type) Ca(2+) channels and NMDA receptors on the proliferating precursors. Excitation through this pathway acts to inhibit expression of the glial fate genes Hes1 and Id2 and increase expression of NeuroD, a positive regulator of neuronal differentiation. These activity-sensing properties of the adult NPCs, when applied as an "excitation-neurogenesis coupling rule" within a Hebbian neural network, predict significant advantages for both the temporary storage and the clearance of memories.}, Author = {Deisseroth, Karl and Singla, Sheela and Toda, Hiroki and Monje, Michelle and Palmer, Theo D. and Malenka, Robert C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Microtubule-Associated Proteins;Cell Differentiation;Animals;Transcription Factors;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Rats;Neuronal Plasticity;Cells, Cultured;Synaptic Transmission;Female;Homeodomain Proteins;Rats, Sprague-Dawley;Hippocampus;03 Adult neurogenesis progenitor source;Rats, Inbred F344;Animals, Newborn;Support, Non-U.S. Gov't;Nerve Net;Neurons;Support, U.S. Gov't, P.H.S.;Calcium Channels, L-Type;Receptors, N-Methyl-D-Aspartate;Nerve Tissue Proteins;Stem Cells;Excitatory Postsynaptic Potentials}, Month = {5}, Nlm_Id = {8809320}, Notes = {there is a supplement for this in omega data}, Number = {4}, Organization = {Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.}, Pages = {535-52}, Pii = {S0896627304002661}, Pubmed = {15157417}, Title = {Excitation-neurogenesis coupling in adult neural stem/progenitor cells}, Uuid = {84F3AFEA-DB36-4E3C-BFF0-88E9825110F8}, Volume = {42}, Year = {2004}, url = {papers/Deisseroth_Neuron2004.pdf}} @article{Del-Turco:2004, Abstract = {The dentate gyrus of rodents is characterized by a highly laminar organization: above a compact granule cell layer, commissural/associational (C/A) fibers terminate on proximal granule cell dendrites and entorhinal fibers terminate on distal granule cell dendrites in a nonoverlapping manner. To gain insights into mechanisms that underlie the formation of this laminar structure, we studied mice deficient for BETA2/NeuroD, a basic helix-loop-helix transcription factor essential for granule cell differentiation. Anterograde tracing was used to label C/A and entorhinal fibers and combined with confocal double immunofluorescence for calbindin, calretinin, parvalbumin, and reelin to visualize putative target cells. The dentate gyrus of mutant mice contained only few granule cells, which formed a cap-like structure adjacent to area CA3. Despite the severe hypoplasia of the dentate gyrus, the remaining BETA2/NeuroD-deficient granule cells expressed mature markers, extended dendrites into the molecular layer, and extended mossy fibers into area CA3. Entorhinal and C/A fibers terminated in a nonoverlapping manner in the dendritic field overlying the rudiment. Entorhinal fibers terminated in the outermost portion of the dentate gyrus where they surrounded reelin-positive Cajal-Retzius cells, and C/A fibers terminated above and within the dentate rudiment. The laminar termination of C/A fibers was closest to normal in zones of the rudiment in which granule cells were densely packed. These data indicate that granule cells are able to differentiate in the absence of BETA2/NeuroD and suggest that the signals underlying the laminar anatomy of the dentate gyrus are present in the absence of most target cells.}, Author = {Del Turco, Domenico and Gebhardt, Carl and Burbach, Guido J. and Pleasure, Samuel J. and Lowenstein, Daniel H. and Deller, Thomas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {gamma-Aminobutyric Acid;Research Support, Non-U.S. Gov't;Animals;DNA-Binding Proteins;Trans-Activators;Mice, Mutant Strains;Neural Pathways;Phosphopyruvate Hydratase;Female;Pyramidal Cells;Calcium-Binding Protein, Vitamin D-Dependent;Research Support, U.S. Gov't, P.H.S.;Parvalbumins;Dentate Gyrus;Mice;Immunohistochemistry;Nerve Tissue Proteins;Phytohemagglutinins}, Month = {9}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Clinical Neuroanatomy, J.W. Goethe University, D-60590 Frankfurt/Main, Germany.}, Pages = {81-95}, Pubmed = {15281081}, Title = {Laminar organization of the mouse dentate gyrus: insights from BETA2/Neuro D mutant mice}, Uuid = {AD8B17DF-A3E5-11DA-AB00-000D9346EC2A}, Volume = {477}, Year = {2004}, url = {papers/DelTurco_JCompNeurol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20239}} @article{Deloulme:1996, Abstract = {We have examined the regulation of neuron-specific gamma-enolase gene (NSE) expression in oligodendrocytes at various steps of their differentiation/maturation. We have demonstrated for the first time that NSE is expressed in oligodendroglial cells in vitro and in vivo, and only at a certain stage of differentiation. A heterogeneity of the gamma subunit was observed in cultured oligodendrocytes and the same one was found in adult rat brain. The level of gamma mRNA increased when precursor cells differentiated into oligodendrocytes. By contrast, no significant change in alpha-enolase gene expression was observed. High NSE (gamma gamma and alpha gamma) enolase activity was detected in cultured oligodendrocytes. Treatment with basic fibroblast growth factor, which stimulates the proliferation of oligodendrocyte precursor cells and reversibly blocks their differentiation, resulted in lower alpha gamma- and gamma gamma-enolase activities in these cells, but it enhanced alpha alpha-enolase activity slightly. These data indicate that gamma-enolase gene expression is associated with the differentiation of the oligodendrocytes and that it is repressed in adult fully mature cells.}, Author = {Deloulme, J. C. and Lucas, M. and Gaber, C. and Bouillon, P. and Keller, A. and Eclancher, F. and Sensenbrenner, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Isoenzymes;01 Adult neurogenesis general;Aging;Tissue Distribution;Research Support, Non-U.S. Gov't;Molecular Sequence Data;Cell Differentiation;Rats;24 Pubmed search results 2008;Phosphopyruvate Hydratase;Gene Expression;Amino Acid Sequence;Animals;Brain;Oligodendroglia;Cells, Cultured;Fibroblast Growth Factor 2}, Medline = {96365675}, Month = {3}, Nlm_Id = {2985190R}, Number = {3}, Organization = {Laboratoire de Neurobiologie Ontog{\'e}nique, Centre de Neurochimie du CNRS, Strasbourg, France.}, Pages = {936-45}, Pubmed = {8769852}, Title = {Expression of the neuron-specific enolase gene by rat oligodendroglial cells during their differentiation}, Uuid = {200C7D62-081D-4B01-B703-FD2C7D8034B7}, Volume = {66}, Year = {1996}} @article{Demarque:2004, Abstract = {Glutamate transporters are operative at an early developmental stage well before synapse formation, but their functional significance has not been determined. We now report that blockade of glutamate transporters in the immature neocortex generates recurrent NMDA receptor-mediated currents associated with synchronous oscillations of [Ca2+]i in the entire neuronal population. Intracerebroventricular injections of the blocker to pups generate seizures that are prevented by coinjections of NMDA receptor blockers. Therefore, the early expression of glutamate transporters plays a central role to prevent the activation by local glutamate concentrations of NMDA receptors and the generation of seizures that may alter the construction of cortical networks. A dysfunction of glutamate transporters may be a central event in early infancy epilepsy syndromes.}, Author = {Demarque, Michael and Villeneuve, Nathalie and Manent, Jean-Bernard B. and Becq, H{\'e}l\`{e}ne and Represa, Alfonso and Ben-Ari, Yehezkel and Aniksztejn, Laurent}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Calcium Signaling;Animals;Rats;Seizures;Glutamic Acid;21 Epilepsy;Neocortex;Excitatory Amino Acid Agonists;Aspartic Acid;Patch-Clamp Techniques;Amino Acid Transport System X-AG;Rats, Wistar;Biological Clocks;Animals, Newborn;N-Methylaspartate;Neurons;21 Neurophysiology;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {8102140}, Number = {13}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e/Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U29, Parc Scientifique de Luminy, 13009 Marseille, France.}, Pages = {3289-94}, Pii = {24/13/3289}, Pubmed = {15056708}, Title = {Glutamate transporters prevent the generation of seizures in the developing rat neocortex}, Uuid = {4B2D3113-9F3B-43E4-98BB-08CA5D162AAB}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5338-03.2004}} @article{Dememes:1975, Abstract = {The macrophagic and neuroglial reactions occurring in the corpus callosum following transection were studied by radioautography and electron microscopy in adult rats. The animals were killed at intervals ranging from two days to three months after operation. In the lesion itself and the immediately surrounding tissues an important proliferation of hematogenous macrophages was observed. Further away from the point of severance no significant numerical increase in the neuroglia could be noted. However the accumulation of glial filaments, lipid droplets and fragments of myelin sheath in the astrocytes seems to indicate that this type of cell plays a phagocytic role. As for the oligodendrocytes, there is no evidence of their participation in phagocytosis, whereas the microglia plays an important part. In the removal of the tissue debris the role and the origin of the macrophages and the microglia are discussed, as is the share of each type of cell in the phagocytic response depending on the extent of the lesion and the degree of axonal degeneration.}, Author = {Dem\^{e}mes, D. and Marty, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0044-3107}, Journal = {Z Mikrosk Anat Forsch}, Keywords = {Neuroglia;Wallerian Degeneration;Nerve Degeneration;Rats;Microscopy, Electron;Autoradiography;English Abstract;Not relevant;Astrocytes;11 Glia;Macrophages;Animals;Oligodendroglia;Phagocytosis;Corpus Callosum}, Medline = {77083555}, Nlm_Id = {0413637}, Number = {6}, Pages = {1104-17}, Pubmed = {1234813}, Title = {[Macrophagic and neuroglial reactions during axonic degeneration following transection of corpus callosum: a radioautographic and ultrastructural study]}, Uuid = {B819D836-9629-46E1-8CF3-697BB1C4FDA2}, Volume = {89}, Year = {1975}} @article{Demir:1998, Abstract = {The piriform cortex is a temporal lobe structure with a very high seizure susceptibility. To investigate the spatiotemporal characteristics of epileptiform activity, slices of piriform cortex were examined by imaging electrical activity with a voltage-sensitive fluorescent dye. Discharge activity was studied for different sites of stimulation and different planes of slicing along the anterior-posterior axis. Epileptiform behavior was elicited either by disinhibition with a gamma-aminobutyric acid-A receptor antagonist or by induction with a transient period of spontaneous bursting in low-chloride medium. Control activity recorded with fluorescent dye had the same pharmacological and temporal characteristics as control activity reported previously with microelectrodes. Simultaneous optical and extracellular microelectrode recordings of epileptiform discharges showed the same duration, latency, and all-or-none character as described previously with microelectrodes. Under all conditions examined, threshold electrical stimulation applied throughout the piriform cortex evoked all-or-none epileptiform discharges originating in a site that included the endopiriform nucleus, a previously identified site of discharge onset. In induced slices, but not disinhibited slices, the site of onset also included layer VI of the adjoining agranular insular cortex and perirhinal cortex, in slices from anterior and posterior piriform cortex, respectively. These locations had not been identified previously as sites of discharge onset. Thus like the endopiriform nucleus, the deep agranular insular cortex and perirhinal cortex have a very low seizure threshold. Additional subtle differences were noted between the induced and disinhibited models of epileptogenesis. Velocity was determined for discharges after onset, as they propagated outward to the overlying piriform cortex. Propagation in other directions was examined as well. In most cases, velocities were below that for action potential conduction, suggesting that recurrent excitation and/or ephaptic interactions play a role in discharge propagation. Future investigations of the cellular and organizational properties of regions identified in this study should help clarify the neurobiological basis of high seizure susceptibility.}, Author = {Demir, R. and Haberly, L. B. and Jackson, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Brain Mapping;Fluorescent Dyes;Electric Stimulation;Animals;Image Processing, Computer-Assisted;Rats;21 Epilepsy;Epilepsy;Rats, Sprague-Dawley;Male;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Membrane Potentials;Fluorometry;Temporal Lobe;24 Pubmed search results 2008;Pyridinium Compounds;Research Support, Non-U.S. Gov't}, Medline = {99036911}, Month = {11}, Nlm_Id = {0375404}, Number = {5}, Organization = {Center for Neuroscience, University of Wisconsin Medical School, Madison Wisconsin 53706, USA.}, Pages = {2727-42}, Pubmed = {9819277}, Title = {Voltage imaging of epileptiform activity in slices from rat piriform cortex: onset and propagation}, Uuid = {212DADD0-05E6-4A73-869E-052818F464FF}, Volume = {80}, Year = {1998}, url = {papers/Demir_JNeurophysiol1998.pdf}} @article{Demir:2000, Abstract = {The deep piriform region has an unusually high seizure susceptibility. Voltage imaging previously located the sites of epileptiform discharge onset in slices of rat piriform cortex and revealed the spatiotemporal pattern of development of two types of electrical activity during the latent period prior to discharge onset. A ramplike depolarization (onset activity) appears at the site of discharge onset. Onset activity is preceded by a sustained low-amplitude depolarization (plateau activity) at another site, which shows little if any overlap with the site of onset. Because synaptic blockade at either of these two sites blocks discharges, it was proposed that both forms of latent period activity are necessary for the generation of epileptiform discharges and that the onset and plateau sites work together in the amplification of electrical activity. The capacity for amplification was examined here by studying subthreshold responses in slices of piriform cortex using two different in vitro models of epilepsy. Under some conditions electrically evoked responses showed a nonlinear dependence on stimulus current, suggesting amplification by strong polysynaptic excitatory responses. The sites of plateau and onset activity were mapped for different in vitro models of epilepsy and different sites of stimulation. These experiments showed that the site of plateau activity expanded into deep layers of neighboring neocortex in parallel with expansions of the onset site into neocortex. These results provide further evidence that interactions between the sites of onset and plateau activity play an important role in the initiation of epileptiform discharges. The site of plateau activity showed little variation with different stimulation sites in the piriform cortex, but when stimulation was applied in the endopiriform nucleus (in the sites of onset of plateau activity), plateau activity had a lower amplitude and became distributed over a much wider area. These results indicate that in the initiation of epileptiform discharges, the location of the circuit that generates plateau activity is not rigidly defined but can exhibit flexibility.}, Author = {Demir, R. and Haberly, L. B. and Jackson, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Linear Models;Epilepsy;Electric Stimulation;Rats, Sprague-Dawley;21 Epilepsy;21 Neurophysiology;Rats;In Vitro;Brain Mapping;Reaction Time;Animals;Male;Cerebral Cortex;Nonlinear Dynamics;24 Pubmed search results 2008}, Medline = {20134678}, Month = {2}, Nlm_Id = {0375404}, Number = {2}, Organization = {Departments of Physiology and Anatomy and Center for Neuroscience, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA.}, Pages = {1088-98}, Pubmed = {10669520}, Title = {Characteristics of plateau activity during the latent period prior to epileptiform discharges in slices from rat piriform cortex}, Uuid = {DCA49210-3B9E-4664-AD19-BA91A2E9D4AD}, Volume = {83}, Year = {2000}} @article{Demyanenko:2004, Abstract = {We show that the neural cell recognition molecule Close Homolog of L1 (CHL1) is required for neuronal positioning and dendritic growth of pyramidal neurons in the posterior region of the developing mouse neocortex. CHL1 was expressed in pyramidal neurons in a high-caudal to low-rostral gradient within the developing cortex. Deep layer pyramidal neurons of CHL1-minus mice were shifted to lower laminar positions in the visual and somatosensory cortex and developed misoriented, often inverted apical dendrites. Impaired migration of CHL1-minus cortical neurons was suggested by strikingly slower rates of radial migration in cortical slices, failure to potentiate integrin-dependent haptotactic cell migration in vitro, and accumulation of migratory cells in the intermediate and ventricular/subventricular zones in vivo. The restriction of CHL1 expression and effects of its deletion in posterior neocortical areas suggests that CHL1 may regulate area-specific neuronal connectivity and, by extension, function in the visual and somatosensory cortex.}, Author = {Demyanenko, Galina P. and Schachner, Melitta and Anton, Eva and Schmid, Ralf and Feng, Guoping and Sanes, Joshua and Maness, Patricia F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {10}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.}, Pages = {423-37}, Pii = {S0896627304006464}, Pubmed = {15504324}, Title = {Close homolog of L1 modulates area-specific neuronal positioning and dendrite orientation in the cerebral cortex}, Uuid = {C1B3DFF6-882C-4F93-9D65-D89109BCB19A}, Volume = {44}, Year = {2004}, url = {papers/Demyanenko_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.10.016}} @article{Deng:2003, Abstract = {Although the existence of the hepatic oval cell (HOC), the liver stem cell has been known for almost 70 years, little is known about the potential for this adult stem cell to trans-differentiate into cells of other tissues. While their origin remains enigmatic, HOCs share many similarities with hematopoietic stem cells. Recent studies have revealed that a small percentage of HOCs can arise from a bone marrow-derived stem cell source. Here we report that, like bone marrow stem cells, HOCs can survive transplantation to the neonatal mouse brain and show signs of trans-differentiation by adopting the morphology and antigenic phenotype of both macro- and microglia cells. Trans-differentiated microglia cells were functional, showing active phagocytosis when cotransplanted with latex microbeads in vivo. In addition to glial markers, a small number of transplanted HOCs were immunopositive for neuronal markers, but displayed ambiguous phenotype, making their characterization difficult.}, Author = {Deng, Jie and Steindler, Dennis A. and Laywell, Eric D. and Petersen, Bryon E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cell Survival;Cell Differentiation;Animals;Stem Cell Transplantation;Cells, Cultured;Antigens, Ly;Brain;Antigens, Differentiation;Microglia;Mice, Transgenic;Liver;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Neurons;Immunomagnetic Separation;Dicarbethoxydihydrocollidine;Mice;Luminescent Proteins;Stem Cells;Membrane Proteins;Lateral Ventricles;Graft Survival}, Medline = {22777802}, Month = {8}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA.}, Pages = {373-82}, Pii = {S001448860300058X}, Pubmed = {12895448}, Title = {Neural trans-differentiation potential of hepatic oval cells in the neonatal mouse brain}, Uuid = {BCB07045-79CF-43D5-B38A-1C64660013B6}, Volume = {182}, Year = {2003}, url = {papers/Deng_ExpNeurol2003.pdf}} @article{Denk:1996, Abstract = {Recent advances in optical imaging technology have enabled the measurement of Ca2+ dynamics in individual synaptic spines with high time resolution. Results from work using this new technology have confirmed the view that individual synaptic spines can act as functional chemical compartments with independent dynamics of second-messenger concentration. In particular, the ability of Ca2+ to directly mediate Hebbian coincidence detection has been confirmed.}, Author = {Denk, W. and Yuste, R. and Svoboda, K. and Tank, D. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Synapses;Dendrites;Technology, Medical;21 Neurophysiology;21 Calcium imaging;Calcium Channels;Calcium;Microscopy, Fluorescence;Electrophysiology;Receptors, N-Methyl-D-Aspartate;Animals;Optics;review;24 Pubmed search results 2008}, Medline = {96391869}, Month = {6}, Nlm_Id = {9111376}, Number = {3}, Organization = {Bell Laboratories, Lucent Technologies, 700 Mountain Avenue, Murray Hill, New Jersey 07974, USA.}, Pages = {372-8}, Pii = {S0959-4388(96)80122-X}, Pubmed = {8794079}, Title = {Imaging calcium dynamics in dendritic spines}, Uuid = {5EDF194F-F7C5-4F97-9D69-8399A61FDFDD}, Volume = {6}, Year = {1996}} @article{Dennis:2004, Author = {Dennis, Carina}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Odors;Olfactory Pathways;Smell;Olfactory Receptor Neurons;Human;Gene Expression Regulation;Neurosciences;Receptors, Odorant;Animals;13 Olfactory bulb anatomy;news}, Month = {3}, Nlm_Id = {0410462}, Number = {6981}, Pages = {362-4}, Pii = {428362a}, Pubmed = {15042058}, Title = {Neuroscience: the sweet smell of success}, Uuid = {BD1835BD-9C93-4A24-B2BE-EBC345780C96}, Volume = {428}, Year = {2004}, url = {papers/Dennis_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/428362a}} @article{Depaepe:2005, Abstract = {Mechanisms controlling brain size include the regulation of neural progenitor cell proliferation, differentiation, survival and migration. Here we show that ephrin-A/EphA receptor signalling plays a key role in controlling the size of the mouse cerebral cortex by regulating cortical progenitor cell apoptosis. In vivo gain of EphA receptor function, achieved through ectopic expression of ephrin-A5 in early cortical progenitors expressing EphA7, caused a transient wave of neural progenitor cell apoptosis, resulting in premature depletion of progenitors and a subsequent dramatic decrease in cortical size. In vitro treatment with soluble ephrin-A ligands similarly induced the rapid death of cultured dissociated cortical progenitors in a caspase-3-dependent manner, thereby confirming a direct effect of ephrin/Eph signalling on apoptotic cascades. Conversely, in vivo loss of EphA function, achieved through EphA7 gene disruption, caused a reduction in apoptosis occurring normally in forebrain neural progenitors, resulting in an increase in cortical size and, in extreme cases, exencephalic forebrain overgrowth. Together, these results identify ephrin/Eph signalling as a physiological trigger for apoptosis that can alter brain size and shape by regulating the number of neural progenitors.}, Author = {Depaepe, Vanessa and Suarez-Gonzalez, Nathalie and Dufour, Audrey and Passante, Lara and Gorski, Jessica A. and Jones, Kevin R. and Ledent, Catherine and Vanderhaeghen, Pierre}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {10 Development;Signal Transduction;Animals;Caspase 3;Ephrins;Brain;Receptors, Eph Family;Ephrin-A5;Mutation;Apoptosis;Mice, Transgenic;Caspases;research support, non-u.s. gov't;10 circuit formation;research support, u.s. gov't, p.h.s.;Neurons;Organ Size;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Stem Cells}, Month = {6}, Nlm_Id = {0410462}, Number = {7046}, Organization = {Institut de Recherches Interdisciplinaires en Biologie Humaine et Mol{\'e}culaire (IRIBHM), University of Brussels, Campus Erasme, 808 Route de Lennik, B-1070 Brussels, Belgium.}, Pages = {1244-50}, Pii = {nature03651}, Pubmed = {15902206}, Title = {Ephrin signalling controls brain size by regulating apoptosis of neural progenitors}, Uuid = {FEC22ED6-D1D8-4AF0-B632-65B1AE92207A}, Volume = {435}, Year = {2005}, url = {papers/Depaepe_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03651}} @article{Desai:2000, Abstract = {During early stages of cerebral cortical development, progenitor cells in the ventricular zone are multipotent, producing neurons of many layers over successive cell divisions. The laminar fate of their progeny depends on environmental cues to which the cells respond prior to mitosis. By the end of neurogenesis, however, progenitors are lineally committed to producing upper-layer neurons. Here we assess the laminar fate potential of progenitors at a middle stage of cortical development. The progenitors of layer 4 neurons were first transplanted into older brains in which layer 2/3 was being generated. The transplanted neurons adopted a laminar fate appropriate for the new environment (layer 2/3), revealing that layer 4 progenitors are multipotent. Mid-stage progenitors were then transplanted into a younger environment, in which layer 6 neurons were being generated. The transplanted neurons bypassed layer 6, revealing that layer 4 progenitors have a restricted fate potential and are incompetent to respond to environmental cues that trigger layer 6 production. Instead, the transplanted cells migrated to layer 4, the position typical of their origin, and also to layer 5, a position appropriate for neither the host nor the donor environment. Because layer 5 neurogenesis is complete by the stage that progenitors were removed for transplantation, restrictions in laminar fate potential must lag behind the final production of a cortical layer. These results suggest that a combination of intrinsic and environmental cues controls the competence of cortical progenitor cells to produce neurons of different layers.}, Author = {Desai, A. R. and McConnell, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Models, Biological;Perfusion;10 Development;Cell Transplantation;Phenotype;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Time Factors;Ferrets;Nervous System;Animals;Cell Movement;Cerebral Cortex;Neurons;Cell Lineage}, Medline = {20311354}, Month = {7}, Nlm_Id = {8701744}, Number = {13}, Organization = {Department of Biological Sciences, Stanford University, Stanford, California 94305, USA. suemcc\@stanford.edu}, Pages = {2863-72}, Pubmed = {10851131}, Title = {Progressive restriction in fate potential by neural progenitors during cerebral cortical development}, Uuid = {177F6EE5-5817-400E-B83D-531365CD6E12}, Volume = {127}, Year = {2000}, url = {papers/Desai_Development2000.pdf}} @article{Desai:2002, Abstract = {The mechanisms underlying experience-dependent plasticity and refinement of central circuits are not yet fully understood. A non-Hebbian form of synaptic plasticity, which scales synaptic strengths up or down to stabilize firing rates, has recently been discovered in cultured neuronal networks. Here we demonstrate the existence of a similar mechanism in the intact rodent visual cortex. The frequency of miniature excitatory postsynaptic currents (mEPSCs) in principal neurons increased steeply between post-natal days 12 and 23. There was a concomitant decrease in mEPSC amplitude, which was prevented by rearing rats in complete darkness from 12 days of age. In addition, as little as two days of monocular deprivation scaled up mEPSC amplitude in a layer- and age-dependent manner. These data indicate that mEPSC amplitudes can be globally scaled up or down as a function of development and sensory experience, and suggest that synaptic scaling may be involved in the activity-dependent refinement of cortical connectivity.}, Author = {Desai, Niraj S. and Cudmore, Robert H. and Nelson, Sacha B. and Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;in vitro;Rats, Long-Evans;Animals;Synapses;Aging;Neuronal Plasticity;Rats;research support, u.s. gov't, p.h.s. ;Patch-Clamp Techniques;Sensory Deprivation;in vitro ;Darkness;Receptors, AMPA;Tetrodotoxin;Critical Period (Psychology);Receptors, GABA-A;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Neurons;GABA Antagonists;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Visual Cortex;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Department of Biology and Volen National Center for Complex Systems, MS 008, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA.}, Pages = {783-9}, Pii = {nn878}, Pubmed = {12080341}, Title = {Critical periods for experience-dependent synaptic scaling in visual cortex}, Uuid = {7E3AFD59-B696-47EB-8F10-2E56726FEC45}, Volume = {5}, Year = {2002}, url = {papers/Desai_NatNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn878}} @article{Destexhe:2006, Abstract = {Neuronal networks in vivo are characterized by considerable spontaneous activity, which is highly complex and intrinsically generated by a combination of single-cell electrophysiological properties and recurrent circuits. As seen, for example, during waking compared with being asleep or under anesthesia, neuronal responsiveness differs, concomitant with the pattern of spontaneous brain activity. This pattern, which defines the state of the network, has a dramatic influence on how local networks are engaged by inputs and, therefore, on how information is represented. We review here experimental and theoretical evidence of the decisive role played by stochastic network states in sensory responsiveness with emphasis on activated states such as waking. From single cells to networks, experiments and computational models have addressed the relation between neuronal responsiveness and the complex spatiotemporal patterns of network activity. The understanding of the relation between network state dynamics and information representation is a major challenge that will require developing, in conjunction, specific experimental paradigms and theoretical frameworks.}, Author = {Destexhe, Alain and Contreras, Diego}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Wakefulness;research support, n.i.h., extramural ;Attention;Synapses;Evoked Potentials;Neural Networks (Computer);Humans;review;Neocortex;Anesthesia;Sleep;research support, non-u.s. gov't ;Computer Simulation;Nerve Net;Neurons;21 Neurophysiology;24 Pubmed search results 2008;Models, Neurological;Stochastic Processes}, Month = {10}, Nlm_Id = {0404511}, Number = {5796}, Organization = {Integrative and Computational Neuroscience Unit (UNIC), CNRS, Gif sur Yvette, France. Destexhe\@iaf.cnrs-gif.fr}, Pages = {85-90}, Pii = {314/5796/85}, Pubmed = {17023650}, Title = {Neuronal computations with stochastic network states}, Uuid = {11EB670A-046C-436B-9E9E-387B57A6E405}, Volume = {314}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1127241}} @article{Deuel:2006, Abstract = {Although mutations in the human doublecortin gene (DCX) cause profound defects in cortical neuronal migration, a genetic deletion of Dcx in mice produces a milder defect. A second locus, doublecortin-like kinase (Dclk), encodes a protein with similar "doublecortin domains" and microtubule stabilization properties that may compensate for Dcx. Here, we generate a mouse with a Dclk mutation that causes no obvious migrational abnormalities but show that mice mutant for both Dcx and Dclk demonstrate perinatal lethality, disorganized neocortical layering, and profound hippocampal cytoarchitectural disorganization. Surprisingly, Dcx(-/y);Dclk(-/-) mutants have widespread axonal defects, affecting the corpus callosum, anterior commissure, subcortical fiber tracts, and internal capsule. Dcx/Dclk-deficient dissociated neurons show abnormal axon outgrowth and dendritic structure, with defects in axonal transport of synaptic vesicle proteins. Dcx and Dclk may directly or indirectly regulate microtubule-based vesicle transport, a process critical to both neuronal migration and axon outgrowth.}, Author = {Deuel, Thomas A. S. and Liu, Judy S. and Corbo, Joseph C. and Yoo, Seung-Yun Y. and Rorke-Adams, Lucy B. and Walsh, Christopher A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Microtubule-Associated Proteins;Animals;Mice, Mutant Strains;Congenital Abnormalities;Embryo, Mammalian;Neocortex;Synaptic Vesicles;Brain;Cell Movement;Protein-Serine-Threonine Kinases;RNA, Messenger;Axons;Embryo;Dendrites;Neuropeptides;Animals, Newborn;Mice, Knockout;Neurons;Abnormalities;Mice;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Nerve Tissue Proteins;Tissue Survival;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {41-53}, Pii = {S0896-6273(05)00962-1}, Pubmed = {16387638}, Title = {Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth}, Uuid = {D094E506-D974-4AC6-9162-4FB60B50D377}, Volume = {49}, Year = {2006}, url = {papers/Deuel_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.10.038}} @article{Dexter:1977, Abstract = {0092-8674 Journal Article}, Author = {Dexter, T. M. and Scott, D. and Teich, N. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Cell}, Keywords = {Clone Cells;Temperature;Friend murine leukemia virus/*growth &development;Hematopoietic Stem Cells/*cytology;Erythropoietin/pharmacology;EE, DMSO, abstr;Dimethyl Sulfoxide/pharmacology;08 Aberrant cell cycle;Moloney murine leukemia virus/*growth &development;Cell Division;Cell Adhesion;Leukemia, Experimental/*etiology;Cells, Cultured;Animals;Mice;*Hematopoiesis}, Number = {2}, Pages = {355-64}, Pubmed = {912746}, Title = {Infection of bone marrow cells in vitro with FLV: effects on stem cell proliferation, differentiation and leukemogenic capacity}, Uuid = {955E9C42-635D-4A42-9C31-DC345181A089}, Volume = {12}, Year = {1977}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=912746}} @article{Dheen:1994, Abstract = {This study describes the ultrastructural changes in the cuneate nucleus of the streptozotocin-induced diabetic rats at 3, 6, 9, and 12 months post-induction. At 3 and 6 months, post-diabetes, a marked atrophy was observed in the myelinated axons. The atrophic axons showed delamination of myelin sheath, tightly arranged lamellar whorls, vesicular elements and degenerating debris within the electron-lucent axoplasm. At 9 and 12 months post-diabetes, a variety of dystrophic and degenerating axonal profiles and dendrites were seen in neuropil. The dystrophic axonal profiles containing tubulovesicular elements, slit-like clefts, vacuoles, swollen mitochondria, membranous and multigranular bodies appeared to be hypertrophied. The degenerating axon terminals contained swollen mitochondria and clustered spherical agranular vesicles in their electron-dense granular axoplasm. The degenerating dendrites were identified by the presence of swollen mitochondria, dilated ER in the electron-dense cytoplasm and they often formed the synaptic glomeruli with central axon terminals. Macrophages containing lipid bodies and electron-dense elements in their cytoplasm were in the process of phagocytosis. In all the time intervals studied, the somata appeared to be normal and the number of dystrophic and degenerating axonal profiles in the cuneate nucleus of diabetic rats was significantly increased in comparison with age-matched saline injected control rats.}, Author = {Dheen, S. T. and Tay, S. S. and Wong, W. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0021-8359}, Journal = {J Hirnforsch}, Keywords = {Dendrites;Nerve Degeneration;Rats;Presynaptic Terminals;Myelin Sheath;Medulla Oblongata;Not relevant;Rats, Wistar;Mitochondrial Swelling;Microglia;11 Glia;Blood Glucose;Male;Animals;Support, Non-U.S. Gov't;Diabetes Mellitus, Experimental;Axons}, Medline = {94342733}, Nlm_Id = {0421521}, Number = {2}, Organization = {Department of Anatomy, Faculty of Medicine, National University of Singapore, Kent Ridge.}, Pages = {253-62}, Pubmed = {8064142}, Title = {Ultrastructure of the cuneate nucleus in the streptozotocin-induced diabetic rat}, Uuid = {5219A600-F8CC-4D37-BBCB-715E2F23C909}, Volume = {35}, Year = {1994}} @article{Dhillon:2007, Abstract = {There is increasing cumulative evidence that activated mononuclear phagocytes (macrophages/microglia) releasing inflammatory mediators in the CNS are a better correlate of HIV-associated dementia (HAD) than the actual viral load in the brain. Earlier studies on simian HIV/rhesus macaque model of NeuroAIDS confirmed that pathological changes in brains of macaques with encephalitis were associated with up-regulation of platelet-derived growth factor (PDGF) and the chemokine, CXCL10. Because the complex interplay of inflammatory mediators released by macrophages often leads to the induction of neurotoxins in HAD, we hypothesized that PDGF could interact with IFN-gamma to modulate the expression of CXCL10 in these primary virus target cells. Although PDGF alone had no effect on the induction of CXCL10 in human macrophages, in conjunction with IFN-gamma, it significantly augmented the expression of CXCL10 RNA & protein through transcriptional and posttranscriptional mechanisms. Signaling molecules, such as JAK and STATs, PI3K, MAPK, and NF-kappaB were found to play a role in the synergistic induction of CXCL10. Furthermore, PDGF via its activation of p38 MAPK was able to increase the stability of IFN-gamma-induced CXCL10 mRNA. Understanding the mechanisms involved in the synergistic up-regulation of CXCL10 could aid in the development of therapeutic modalities for HAD.}, Author = {Dhillon, Navneet Kaur and Peng, Fuwang and Ransohoff, Richard M. and Buch, Shilpa}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {21 Neurophysiology;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {2985117R}, Number = {5}, Organization = {Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.}, Pages = {2722-30}, Pii = {179/5/2722}, Pubmed = {17709485}, Title = {PDGF synergistically enhances IFN-gamma-induced expression of CXCL10 in blood-derived macrophages: implications for HIV dementia}, Uuid = {A43DA349-9E9C-4793-9E1E-0AF6D31CB9BB}, Volume = {179}, Year = {2007}} @article{Di-Cunto:1998, Abstract = {We have identified a novel serine/threonine kinase belonging to the myotonic dystrophy kinase family. The kinase can be produced in at least two different isoforms: a approximately 240-kDa protein (Citron Rho-interacting kinase, CRIK), in which the kinase domain is followed by the sequence of Citron, a previously identified Rho/Rac binding protein; a approximately 54-kDa protein (CRIK-short kinase (SK)), which consists mostly of the kinase domain. CRIK and CRIK-SK proteins are capable of phosphorylating exogenous substrates as well as of autophosphorylation, when tested by in vitro kinase assays after expression into COS7 cells. CRIK kinase activity is increased severalfold by coexpression of costitutively active Rho, while active Rac has more limited effects. Kinase activity of endogenous CRIK is indicated by in vitro kinase assays after immunoprecipitation with antibodies recognizing the Citron moiety of the protein. When expressed in keratinocytes, full-length CRIK, but not CRIK-SK, localizes into corpuscular cytoplasmic structures and elicits recruitment of actin into these structures. The previously reported Rho-associated kinases ROCK I and II are ubiquitously expressed. In contrast, CRIK exhibits a restricted pattern of expression, suggesting that this kinase may fulfill a more specialized function in specific cell types. 99009084 0021-9258 Journal Article}, Author = {Di Cunto, F. and Calautti, E. and Hsiao, J. and Ong, L. and Topley, G. and Turco, E. and Dotto, G. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {J Biol Chem}, Keywords = {Keratinocytes/enzymology;Protein Binding;Protein-Serine-Threonine Kinases/genetics/*metabolism;Base Sequence;Molecular Sequence Data;Sequence Homology, Amino Acid;CK;Animal;Amino Acid Sequence;Support, U.S. Gov't, P.H.S.;Proteins/*metabolism;Fluorescent Antibody Technique;Support, Non-U.S. Gov't;COS Cells;Cloning, Molecular;Mice;DNA, Complementary}, Number = {45}, Organization = {Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.}, Pages = {29706-11}, Title = {Citron rho-interacting kinase, a novel tissue-specific ser/thr kinase encompassing the Rho-Rac-binding protein Citron}, Uuid = {AD8AF79E-A3E5-11DA-AB00-000D9346EC2A}, Volume = {273}, Year = {1998}, url = {papers/DiCunto_JBiolChem1998.pdf}} @article{Di-Cunto:2000, Abstract = {Citron-kinase (Citron-K) has been proposed by in vitro studies as a crucial effector of Rho in regulation of cytokinesis. To further investigate in vivo its biologic functions, we have inactivated Citron-K gene in mice by homologous recombination. Citron-K-/- mice grow at slower rates, are severely ataxic, and die before adulthood as a consequence of fatal seizures. Their brains display defective neurogenesis, with depletion of specific neuronal populations. These abnormalities arise during development of the central nervous system due to altered cytokinesis and massive apoptosis. Our results indicate that Citron-K is essential for cytokinesis in vivo but only in specific neuronal precursors. Moreover, they suggest a novel molecular mechanism for a subset of human malformative syndromes of the CNS. 20537823 0896-6273 Journal Article}, Author = {Di Cunto, F. and Imarisio, S. and Hirsch, E. and Broccoli, V. and Bulfone, A. and Migheli, A. and Atzori, C. and Turco, E. and Triolo, R. and Dotto, G. P. and Silengo, L. and Altruda, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {Neuron}, Keywords = {Protein-Serine-Threonine Kinases/biosynthesis/deficiency/*genetics;Neurons/*metabolism/pathology;Stem Cells/metabolism/pathology;Neurodegenerative Diseases/complications/*genetics/pathology;Animal;CK;DNA/biosynthesis;Support, Non-U.S. Gov't;Ataxia/etiology;Mice, Knockout;Cell Division/*genetics;Support, U.S. Gov't, P.H.S.;Seizures/etiology;Polyploidy;Apoptosis/*genetics;Cyclin D1/metabolism;Mice;Brain/embryology/pathology}, Number = {1}, Organization = {Department of Genetics, Biology and Biochemistry, University of Torino, Italy. dicunto\@molinette.unito.it}, Pages = {115-27}, Title = {Defective neurogenesis in citron kinase knockout mice by altered cytokinesis and massive apoptosis}, Uuid = {F54293FA-69B4-11DA-A4B6-000D9346EC2A}, Volume = {28}, Year = {2000}, url = {papers/DiCunto_Neuron2000}} @article{Di-Stefano:1996, Abstract = {The most frequent neurological complication of AIDS is a dementia-like syndrome. Power and collaborators (J Virol 1994; 68:4643-4649) have reported an association between the clinical signs of AIDS dementia and the amino acid composition of two positions (305 and 329) within the V3 region of HIV-1 strains amplified from brain tissue. Similarly, we analyzed position 305 in the V3 region of HIV-1 present in the brain or cerebrospinal fluid of 25 nondemented subjects at different clinical stages of HIV-1 infection. Our results are, however, at variance with the findings presented by Power and colleagues. Histidine, found to be common among sequences derived from demented patients, was also present in the majority (16 of 25) of nondemented patients analyzed by us. In the hands of Power and colleagues, sequences derived from nondemented patients contained proline at position 305. None of our patients had proline in this position. We also asked the question whether the presence of a specific amino acid at position 305 of the V3 loop is linked to an increased capacity of HIV-1 isolates to infect primary microglial cells, the major target cell for HIV-1 infection in the brain. Primary HIV-1 isolates derived from blood and cerebrospinal fluid of five patients, two asymptomatic and three AIDS patients, were used to infect microglia cell cultures. Infection was monitored by syncytium formation and by p24 antigen release in the culture supernatant. All but one of the paired blood/CSF isolates replicated in human brain cultures. Replication occurred independently from the amino acid present at position 305 of the V3 region of the viral envelope. Our results indicate that the majority of HIV-1 isolates, even derived during the asymptomatic stage, have the capacity to infect microglial cells. The relevance of viral envelope sequences in determining tropism for microglial cells and development of neurological symptoms remains an open question.}, Author = {Di Stefano, M. and Wilt, S. and Gray, F. and Dubois-Dalcq, M. and Chiodi, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0889-2229}, Journal = {AIDS Res Hum Retroviruses}, Keywords = {Giant Cells;Research Support, Non-U.S. Gov't;Molecular Sequence Data;Adult;HIV Core Protein p24;Human;AIDS Dementia Complex;HIV-1;11 Glia;Microglia;Amino Acid Sequence;Acquired Immunodeficiency Syndrome;Cells, Cultured;Support, Non-U.S. Gov't;Humans;HIV Envelope Protein gp120}, Medline = {96296958}, Month = {4}, Nlm_Id = {8709376}, Number = {6}, Organization = {Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden.}, Pages = {471-6}, Pubmed = {8679301}, Title = {HIV type 1 V3 sequences and the development of dementia during AIDS}, Uuid = {0771BF68-089F-47BF-80C0-1575449044BE}, Volume = {12}, Year = {1996}} @article{Dietz:2005, Abstract = {The mitral-granule reciprocal synapse shapes the response of the olfactory bulb to odour stimuli by mediating lateral and reciprocal inhibition. We investigated the short-term plasticity of both the mitral-to-granule excitatory synapse and the granule-to-mitral inhibitory synapse in rat olfactory bulb slices, using whole-cell patch clamp recordings. The granule-to-mitral inhibitory synapse invariably exhibited paired-pulse depression at interstimulus intervals of less than a second, while the mitral-to-granule excitatory synapse showed heterogeneous responses, which on average yielded a moderate facilitation. Trains of stimuli led to a much greater depression at the granule-to-mitral synapse than at the mitral-to-granule synapse. Since mitral cells commonly respond to odours by burst firing with each inhalation cycle, we used bursts of stimuli to study recovery from depression. We found that recovery from depression induced by fast trains of stimuli was more rapid at the mitral-to-granule synapse than at the granule-to-mitral synapse. In addition, depression was enhanced by higher calcium concentrations, suggesting at least partial contribution of presynaptic mechanisms to short-term depression. The observed short-term plasticity could enable mitral cells to overcome autoinhibition and increase action potential propagation along lateral dendrites by burst firing.}, Author = {Dietz, Shelby B. and Murthy, Venkatesh N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {gamma-Aminobutyric Acid;research support, n.i.h., extramural ;Animals;Synapses;Rats;Neuronal Plasticity;Synaptic Transmission;research support, u.s. gov't, non-p.h.s. ;Patch-Clamp Techniques;Calcium;Time Factors;Odors;Dendrites;research support, non-u.s. gov't ;Temperature;Action Potentials;Olfactory Bulb;Neurons;21 Neurophysiology;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {0266262}, Number = {Pt 2}, Organization = {Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA. vnmurthy\@fas.harvard.edu.}, Pages = {475-88}, Pii = {jphysiol.2005.095844}, Pubmed = {16166156}, Title = {Contrasting short-term plasticity at two sides of the mitral-granule reciprocal synapse in the mammalian olfactory bulb}, Uuid = {563CAD52-0C7D-4B04-A2C9-B1A7012D3098}, Volume = {569}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2005.095844}} @article{Dietz:2003, Abstract = {Human institutions--ways of organizing activities--affect the resilience of the environment. Locally evolved institutional arrangements governed by stable communities and buffered from outside forces have sustained resources successfully for centuries, although they often fail when rapid change occurs. Ideal conditions for governance are increasingly rare. Critical problems, such as transboundary pollution, tropical deforestation, and climate change, are at larger scales and involve nonlocal influences. Promising strategies for addressing these problems include dialogue among interested parties, officials, and scientists; complex, redundant, and layered institutions; a mix of institutional types; and designs that facilitate experimentation, learning, and change.}, Author = {Dietz, Thomas and Ostrom, Elinor and Stern, Paul C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1095-9203}, Journal = {Science}, Month = {12}, Nlm_Id = {0404511}, Number = {5652}, Organization = {Environmental Science and Policy Program and Departments of Sociology and Crop and Soil Sciences, Michigan State University, East Lansing, MI 48824, USA.}, Pages = {1907-12}, Pii = {302/5652/1907}, Pubmed = {14671286}, Title = {The struggle to govern the commons}, Uuid = {1E2A77E3-6E60-45C6-ABF0-E7DED5662DD9}, Volume = {302}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1091015}} @article{Dijkstra:2001, Abstract = {CD81 (TAPA), a member of the tetraspanin family of proteins, is upregulated by astrocytes and microglia after traumatic injury to the rat central nervous system (CNS). To further understand the role of CD81 in the microglial response to injury, we analysed the functional effects of a CD81 antibody, AMP1, on cultured rat microglia. We found that AMP1 suppressed microglial proliferation in a dose-dependent manner. Furthermore, AMP1 stimulated myelin phagocytosis, probably by opsonizing the myelin. The phagocytosis of latex beads, as well as the production of nitric oxide, were not significantly influenced by AMP1. These data indicate that CD81 is involved in an important subset of microglial effector functions after CNS injury.}, Author = {Dijkstra, S. and Geisert, E. E. and Dijkstra, C. D. and B{\"a}r, P. R. and Joosten, E. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Membrane Proteins;Rats;Myelin Sheath;Spinal Cord Injuries;Antigens, CD;Rats, Wistar;11 Glia;Microglia;Cell Division;Nitric Oxide;Microspheres;Cells, Cultured;Animals;Phagocytosis;Antibodies;In Vitro}, Medline = {21136064}, Month = {3}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Experimental Neurology, UMC Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands. s.dijkstra\@neuro.azu.nl}, Pages = {151-9}, Pii = {S0165572801002405}, Pubmed = {11240026}, Title = {CD81 and microglial activation in vitro: proliferation, phagocytosis and nitric oxide production}, Uuid = {74EC884A-DA5D-4FB3-83F7-30FCD60E0D42}, Volume = {114}, Year = {2001}} @article{Dill:1981, Author = {Dill, R. C. and Scott, M. C. and Porter, R. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Epilepsy;24 Pubmed search results 2008;Electroencephalography;21 Epilepsy;21 Neurophysiology;Cats;Action Potentials;Pressure;Penicillin G;Research Support, U.S. Gov't, Non-P.H.S.;Blood Pressure;Animals;Cerebral Cortex;Freezing;Stomach}, Medline = {81261112}, Month = {8}, Nlm_Id = {0370712}, Number = {2}, Pages = {534-41}, Pubmed = {7262253}, Title = {Changes in the rate of cortical epileptiform activity by increased intragastric pressure in cats}, Uuid = {39F46E2E-1757-44FC-BA55-E7FC694259A5}, Volume = {73}, Year = {1981}} @article{Dingli:2007, Abstract = {Many tumors derive from the transformation of normal stem cells into cancer stem cells that retain their self-renewal capacity. This modern view of cancer has provided a natural explanation for the striking parallels which exist between these two different types of self-renewing cells. Here we develop a simple mathematical model to investigate the implications of this concept regarding the evolution of tumors in the hematopoietic system. Our results unequivocally demonstrate that stochastic effects related to the finite size of the active stem cell population have a profound influence on the dynamics of cancer evolution. For input parameters compatible with both the natural history of human cancer and mouse models, our results show how stochastic dynamics alone may lead to both remission in some cases and rapid expansion in others.}, Author = {Dingli, David and Traulsen, Arne and Pacheco, Jorge M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1551-4005}, Journal = {Cell Cycle}, Keywords = {Models, Biological;Hematologic Neoplasms;Cell Differentiation;research support, non-u.s. gov't;Hematopoietic Stem Cells;Neoplastic Stem Cells;Cell Proliferation;Stochastic Processes;09 Evolutionary dynamics;Computer Simulation;22 Stem cells;22 Cancer;Animals;Disease Progression;Humans;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {101137841}, Number = {4}, Organization = {Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts 02138, USA. dingli\@fas.harvard.edu}, Pages = {461-6}, Pii = {3853}, Pubmed = {17329969}, Title = {Stochastic dynamics of hematopoietic tumor stem cells}, Uuid = {9D99B9F2-FC34-4B50-93A4-EE13CB1B7EF6}, Volume = {6}, Year = {2007}, url = {papers/Dingli_CellCycle2007.pdf}} @article{Dingli:2007a, Abstract = {Most tissues in metazoans undergo continuous turnover due to cell death or epithelial shedding. Since cellular replication is associated with an inherent risk of mutagenesis, tissues are maintained by a small group of stem cells (SCs) that replicate slowly to maintain their own population and that give rise to differentiated cells. There is increasing evidence that many tumors are also maintained by a small population of cancer stem cells that may arise by mutations from normal SCs. SC replication can be either symmetric or asymmetric. The former can lead to expansion of the SC pool. We describe a simple model to evaluate the impact of (a)symmetric SC replication on the expansion of mutant SCs and to show that mutations that increase the probability of asymmetric replication can lead to rapid mutant SC expansion in the absence of a selective fitness advantage. Mutations in several genes can lead to this process and may be at the root of the carcinogenic process.}, Author = {Dingli, David and Traulsen, Arne and Michor, Franziska}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {1553-7358}, Journal = {PLoS Comput Biol}, Keywords = {Models, Biological;Mutation;Cell Transformation, Neoplastic;Cell Proliferation;Stem Cells;Evolution;Neoplasms;Animals;Humans;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {101238922}, Number = {3}, Organization = {Program for Evolutionary Dynamics, Harvard University, Cambridge, Massachusetts, United States of America. dingli\@fas.harvard.edu}, Pages = {e53}, Pii = {06-PLCB-RA-0506R1}, Pubmed = {17367205}, Title = {(A)symmetric stem cell replication and cancer}, Uuid = {D6FFEE19-53E1-4881-833A-EAAC782C2669}, Volume = {3}, Year = {2007}, url = {papers/Dingli_PLoSComputBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.0030053}} @article{Dittgen:2004, Abstract = {It is becoming increasingly clear that single cortical neurons encode complex and behaviorally relevant signals, but efficient means to study gene functions in small networks and single neurons in vivo are still lacking. Here, we establish a method for genetic manipulation and subsequent phenotypic analysis of individual cortical neurons in vivo. First, lentiviral vectors are used for neuron-specific gene delivery from alpha-calcium/calmodulin-dependent protein kinase II or Synapsin I promoters, optionally in combination with gene knockdown by means of U6 promoter-driven expression of short-interfering RNAs. Second, the phenotypic analysis at the level of single cortical cells is carried out by using two-photon microscopy-based techniques: high-resolution two-photon time-lapse imaging is used to monitor structural dynamics of dendritic spines and axonal projections, whereas cellular response properties are analyzed electrophysiologically by two-photon microscopy directed whole-cell recordings. This approach is ideally suited for analysis of gene functions in individual neurons in the intact brain.}, Author = {Dittgen, Tanjew and Nimmerjahn, Axel and Komai, Shoji and Licznerski, Pawel and Waters, Jack and Margrie, Troy W. and Helmchen, Fritjof and Denk, Winfried and Brecht, Michael and Osten, Pavel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Electrophysiology;Animals;Image Processing, Computer-Assisted;RNA, Small Nuclear;Phenotype;Recombinant Proteins;Lentivirus;15 Retrovirus mechanism;23 Technique;Hippocampus;Mice, Inbred C57BL;RNA, Small Interfering;Ca(2+)-Calmodulin Dependent Protein Kinase;Green Fluorescent Proteins;Genetic Vectors;Synapsins;Neurons;Photons;Mice;Microscopy;24 Pubmed search results 2008;Promoter Regions (Genetics);Research Support, Non-U.S. Gov't}, Month = {12}, Nlm_Id = {7505876}, Number = {52}, Organization = {Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.}, Pages = {18206-11}, Pii = {0407976101}, Pubmed = {15608064}, Title = {Lentivirus-based genetic manipulations of cortical neurons and their optical and electrophysiological monitoring in vivo}, Uuid = {5F8B1ED4-07ED-4677-BFF0-3FBE364A6B6F}, Volume = {101}, Year = {2004}, url = {papers/Dittgen_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0407976101}} @article{Dityatev:2003, Abstract = {1471-003x Journal Article Review Review, Academic}, Author = {Dityatev, A. and Schachner, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {Human;11 Glia;Neuronal Plasticity/*physiology;Neurons/physiology;Support, Non-U.S. Gov't;Animals;G pdf;Extracellular Matrix Proteins/*physiology;Neuroglia/physiology}, Number = {6}, Organization = {Zentrum fur Molekulare Neurobiologie, University of Hamburg, Martinistr. 52, 20246 Hamburg, Germany. dityatev\@zmnh.uni-hamburg.de}, Pages = {456-68}, Pubmed = {12778118}, Title = {Extracellular matrix molecules and synaptic plasticity}, Uuid = {28BF6648-0F35-4557-8869-B34C151B8CC2}, Volume = {4}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12778118}} @article{Dobrenis:2005, Abstract = {Microglia, the tissue macrophages of the central nervous system (CNS), intimately interact with neurons physically and through soluble factors that can affect microglial activation state and neuronal survival and physiology. We report here a new mechanism of interaction between these cells, provided by the formation of gap junctions composed of connexin (Cx) 36. Among eight Cxs tested, expression of Cx36 mRNA and protein was found in microglial cultures prepared from human and mouse, and Cx45 mRNA was found in mouse microglial cultures. Electrophysiological measurements found coupling between one-third of human or mouse microglial pairs that averaged below 30 pico-Siemens and displayed electrical properties consistent with Cx36 gap junctions. Importantly, similar frequency of low-strength electrical coupling was also obtained between microglia and neurons in cocultures prepared from neocortical or hippocampal rodent tissue. Lucifer yellow dye coupling between neurons and microglia was observed in 4\%of pairs tested, consistent with the low strength and incidence of electrical coupling. Cx36 expression level and/or the degree of coupling between microglia did not significantly change in the presence of activating agents, including lipopolysaccharide, granulocyte-macrophage colony-stimulating factor, interferon-gamma, and tumor necrosis factor-alpha, except for some reduction of Cx36 protein when exposed to the latter two agents. Our findings that intercellular coupling occurs between neuronal and microglial populations through Cx36 gap junctions have potentially important implications for normal neural physiology and microglial responses in neuronopathology in the mammalian CNS. (c) 2005 Wiley-Liss, Inc.}, Author = {Dobrenis, K. and Chang, H-Y Y. and Pina-Benabou, M. H. and Woodroffe, A. and Lee, S. C. and Rozental, R. and Spray, D. C. and Scemes, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Fluorescent Dyes;Animals;Humans;Encephalitis;Rats;Coculture Techniques;Cells, Cultured;Microglia;Patch-Clamp Techniques;Cell Communication;Rats, Sprague-Dawley;Telencephalon;Mice, Inbred C57BL;Connexins;11 Glia;RNA, Messenger;Animals, Newborn;Neurons;Inflammation Mediators;Isoquinolines;Membrane Potentials;Gliosis;Mice;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't}, Month = {11}, Nlm_Id = {7600111}, Number = {3}, Organization = {Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York.}, Pages = {306-15}, Pubmed = {16211561}, Title = {Human and mouse microglia express connexin36, and functional gap junctions are formed between rodent microglia and neurons}, Uuid = {070598CF-CEF5-11DA-8A64-000D9346EC2A}, Volume = {82}, Year = {2005}, url = {papers/Dobrenis_JNeurosciRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20650}} @article{Dobreva:2006, Abstract = {Vertebrate skeletogenesis involves two processes, skeletal patterning and osteoblast differentiation. Here, we show that Satb2, encoding a nuclear matrix protein, is expressed in branchial arches and in cells of the osteoblast lineage. Satb2-/- mice exhibit both craniofacial abnormalities that resemble those observed in humans carrying a translocation in SATB2 and defects in osteoblast differentiation and function. Multiple osteoblast-specific genes were identified as targets positively regulated by SATB2. In addition, SATB2 was found to repress the expression of several Hox genes including Hoxa2, an inhibitor of bone formation and regulator of branchial arch patterning. Molecular analysis revealed that SATB2 directly interacts with and enhances the activity of both Runx2 and ATF4, transcription factors that regulate osteoblast differentiation. This synergy was genetically confirmed by bone formation defects in Satb2/Runx2 and Satb2/Atf4 double heterozygous mice. Thus, SATB2 acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation.}, Author = {Dobreva, Gergana and Chahrour, Maria and Dautzenberg, Marcel and Chirivella, Laura and Kanzler, Benoit and Fari\~{n}as, Isabel and Karsenty, Gerard and Grosschedl, Rudolf}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {10 Development;Cell Differentiation;Animals;Transcription Factors;Gene Expression Regulation, Developmental;Skull;Osteogenesis;Homeodomain Proteins;Mutation;Activating Transcription Factor 4;Facial Bones;Branchial Region;research support, non-u.s. gov't;Matrix Attachment Region Binding Proteins;Osteoblasts;Genes, Homeobox;Core Binding Factor Alpha 1 Subunit;Craniofacial Abnormalities;Mice, Knockout;Body Patterning;Mice;24 Pubmed search results 2008;Repressor Proteins}, Month = {6}, Nlm_Id = {0413066}, Number = {5}, Organization = {Max-Planck Institute of Immunobiology, Department of Cellular and Molecular Immunology, 79108 Freiburg, Germany.}, Pages = {971-86}, Pii = {S0092-8674(06)00578-2}, Pubmed = {16751105}, Title = {SATB2 is a multifunctional determinant of craniofacial patterning and osteoblast differentiation}, Uuid = {02DBF595-3EE5-4B90-AFF2-ABA5737F4186}, Volume = {125}, Year = {2006}, url = {papers/Dobreva_Cell2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.05.012}} @article{Dobyns:1993, Abstract = {OBJECTIVE--We review the clinical phenotype, pathological changes, and results of cytogenetic and molecular genetic studies in 90 probands with lissencephaly (smooth brain) with emphasis on patients with the classical form (type I). We also describe the recent discovery of the lissencephaly gene (LIS1), deletions of which have been implicated as the cause of this disorder in many patients. DATA SOURCES--We have performed clinical, cytogenetic, and molecular genetic studies of 25 probands with Miller-Dieker syndrome and 65 probands with isolated lissencephaly sequence (ILS). We have further subdivided patients with ILS into those with classical lissencephaly and those with lissencephaly variants. STUDY SELECTION--We consider primarily our own published and unpublished data, but include references to studies of other series of patients with lissencephaly. DATA SYNTHESIS--Visible cytogenetic deletions of 17p13.3 were detected in 14 of 25 Miller-Dieker syndrome probands, and either visible cytogenetic or submicroscopic deletions in 23 (92\%) of 25. Submicroscopic deletions were detected in eight of 45 patients with all types of ILS. If only ILS patients with the classical form are considered, we detected deletions in eight (38\%) of 21. CONCLUSIONS--Deletions of the lissencephaly critical region in chromosome 17p13.3, including LIS1, appear to be the most frequent cause of classical lissencephaly. Molecular cytogenetic studies, particularly fluorescence in situ hybridization, should be performed in all such patients. LIS1 shows homology to genes involved in signal transduction, which may be its function in development of the telencephalon. Other genetic causes of classical lissencephaly and genetic and nongenetic causes of other types of lissencephaly exist and are under study.}, Author = {Dobyns, W. B. and Reiner, O. and Carrozzo, R. and Ledbetter, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0098-7484}, Journal = {JAMA}, Keywords = {Chromosomes, Human, Pair 17;Chromosome Deletion;Brain Diseases;10 Development;In Situ Hybridization, Fluorescence;24 Pubmed search results 2008;DNA;Gene Expression;Polymorphism, Restriction Fragment Length;Congenital Abnormalities;10 genetics malformation;research support, u.s. gov't, p.h.s.;Humans;Brain;Chromosome Mapping;review;Neurons}, Month = {12}, Nlm_Id = {7501160}, Number = {23}, Organization = {Department of Neurology, University of Minnesota Medical School, Minneapolis.}, Pages = {2838-42}, Pubmed = {7907669}, Title = {Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13}, Uuid = {167AC304-50C4-4A35-A1E6-79CAD55BF12E}, Volume = {270}, Year = {1993}} @article{Doetsch:1999, Abstract = {Neural stem cells reside in the subventricular zone (SVZ) of the adult mammalian brain. This germinal region, which continually generates new neurons destined for the olfactory bulb, is composed of four cell types: migrating neuroblasts, immature precursors, astrocytes, and ependymal cells. Here we show that SVZ astrocytes, and not ependymal cells, remain labeled with proliferation markers after long survivals in adult mice. After elimination of immature precursors and neuroblasts by an antimitotic treatment, SVZ astrocytes divide to generate immature precursors and neuroblasts. Furthermore, in untreated mice, SVZ astrocytes specifically infected with a retrovirus give rise to new neurons in the olfactory bulb. Finally, we show that SVZ astrocytes give rise to cells that grow into multipotent neurospheres in vitro. We conclude that SVZ astrocytes act as neural stem cells in both the normal and regenerating brain.}, Author = {Doetsch, F. and Caille, I. and Lim, D. A. and Garcia-Verdugo, J. M. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Cell}, Keywords = {Brain/cytology/physiology;Glial Fibrillary Acidic Protein/genetics/metabolism;02 Adult neurogenesis migration;03 Adult neurogenesis progenitor source;Cerebral Ventricles/*cytology/physiology;Regeneration;Chick Embryo;Animal;Olfactory Bulb;Support, U.S. Gov't, P.H.S.;Astrocytes/*cytology;Support, Non-U.S. Gov't;Male;B-10a;Mice;Stem Cells/*cytology}, Number = {6}, Organization = {The Rockefeller University, New York, New York 10021, USA.}, Pages = {703-16.}, Title = {Subventricular zone astrocytes are neural stem cells in the adult mammalian brain}, Uuid = {7710ED33-68D7-11DA-A4B6-000D9346EC2A}, Volume = {97}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10380923}} @article{Doetsch:2005, Abstract = {Adult neurogenesis occurs in most species and is regulated by a wide variety of environmental and pharmacological challenges. The functional integration of neurons generated in the adult was first demonstrated in songbirds more than two decades ago. In the adult mammalian brain, neurons are continuously generated in two structures, the olfactory bulb and the hippocampus. Current evidence suggests that adult-born immature neurons have distinct electrophysiological properties from old neurons, and proposed roles in a variety of functions including olfaction, learning and mood regulation.}, Author = {Doetsch, Fiona and Hen, Rene}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Departments of Pathology, Neurology and Center for Neurobiology and Behavior, Columbia University, 630W 168(th) Street, NYC, NY 10032, USA.}, Pages = {121-8}, Pii = {S0959-4388(05)00019-X}, Pubmed = {15721754}, Title = {Young and excitable: the function of new neurons in the adult mammalian brain}, Uuid = {BC296855-C811-491D-823A-45CA9CB0A72C}, Volume = {15}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.01.018}} @article{Doetsch:1997, Abstract = {The adult mammalian subventricular zone (SVZ) contains stem cells that give rise to neurons and glia. In vivo, SVZ progeny migrate 3-8 mm to the olfactory bulb, where they form neurons. We show here that the SVZ of the lateral wall of the lateral ventricles in adult mice is composed of neuroblasts, glial cells, and a novel putative precursor cell. The topographical organization of these cells suggests how neurogenesis and migration are integrated in this region. Type A cells had the ultrastructure of migrating neuronal precursors. These cells were arranged as chains parallel to the walls of the ventricle and were polysialylated neural adhesion cell molecule- (PSA-NCAM), TuJ1- (beta- tubulin), and nestin-positive but GFAP- and vimentin-negative. Chains of Type A cells were ensheathed by two ultrastructurally distinct astrocytes (Type B1 and B2) that were GFAP-, vimentin-, and nestin- positive but PSA-NCAM- and TuJ1-negative. Type A and B2 (but not B1) cells incorporated [3H]thymidine. The most actively dividing cell in the SVZ corresponded to Type C cells, which had immature ultrastructural characteristics and were nestin-positive but negative to the other markers. Type C cells formed focal clusters closely associated with chains of Type A cells. Whereas Type C cells were present throughout the SVZ, they were not found in the rostral migratory stream that links the SVZ with the olfactory bulb. These results suggest that chains of migrating neuroblasts in the SVZ may be derived from Type C cells. Our results provide a topographical model for the adult SVZ and should serve as a basis for the in vivo identification of stem cells in the adult mammalian brain.}, Author = {Doetsch, F. and Garcia-Verdugo, J. M. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci}, Keywords = {02 Adult neurogenesis migration;Image Processing, Computer-Assisted;Female;Microscopy, Electron;Immunohistochemistry;B-7;Thymidine/metabolism;Autoradiography;Animal;Support, U.S. Gov't, P.H.S.;Male;Mice;Cerebral Ventricles/*cytology/metabolism/ultrastructure}, Number = {13}, Organization = {The Rockefeller University, New York, New York 10021, USA.}, Pages = {5046-61.}, Title = {Cellular composition and three-dimensional organization of the subventricular germinal zone in the adult mammalian brain}, Uuid = {8EFAF554-4A23-4404-A7AE-C1B72245A2A8}, Volume = {17}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9185542}} @article{Doetsch:2002, Abstract = {The subventricular zone (SVZ) is the largest germinal layer in the adult mammalian brain and comprises stem cells, transit-amplifying progenitors, and committed neuroblasts. Although the SVZ contains the highest concentration of dividing cells in the adult brain, the intracellular mechanisms controlling their proliferation have not been elucidated. We show here that loss of the cyclin-dependent kinase inhibitor p27Kip1 has very specific effects on a population of CNS progenitors responsible for adult neurogenesis. Using bromodeoxyuridine and [(3)H]thymidine incorporation to label cells in S phase and cell- specific markers and electron microscopy to identify distinct cell types, we compared the SVZ structure and proliferation characteristics of wild-type and p27Kip1-null mice. Loss of p27Kip1 had no effect on the number of stem cells but selectively increased the number of the transit-amplifying progenitors concomitantly with a reduction in the number of neuroblasts. We conclude that cell-cycle regulation of SVZ adult progenitors is remarkably cell-type specific, with p27Kip1 being a key regulator of the cell division of the transit-amplifying progenitors.}, Author = {Doetsch, F. and Verdugo, J. M. and Caille, I. and Alvarez-Buylla, A. and Chao, M. V. and Casaccia-Bonnefil, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {6}, Organization = {Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.}, Pages = {2255-64.}, Title = {Lack of the cell-cycle inhibitor p27Kip1 results in selective increase of transit-amplifying cells for adult neurogenesis}, Uuid = {B5B7BC68-2BD1-460A-81AA-D2CFE5B72B16}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11896165%20http://www.jneurosci.org/cgi/content/full/22/6/2255%20http://www.jneurosci.org/cgi/content/abstract/22/6/2255}} @article{Doetsch:2003, Abstract = {Glia are the most numerous cells in the brain, and their many diverse functions highlight their essential role in the nervous system. Recent studies have revealed an unexpected new role for glia in a wide variety of species, that of stem cells/progenitors in the adult and embryonic brain. Differentiation along the glial lineage may be a default state of development reflected in the progression of stem cells along the neuroepithelial-->radial glia-->astrocyte lineage. 1097-6256 Journal Article Review Review, Academic}, Author = {Doetsch, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Nat Neurosci}, Keywords = {01 Adult neurogenesis general;Astrocytes/cytology;Cell Differentiation/*physiology;Neurons/*cytology/physiology;Epithelial Cells;Neuroglia/classification/*cytology/physiology;Stem Cells/*metabolism;Central Nervous System/cytology/embryology/physiology;Lateral Ventricles;Animals;Support, Non-U.S. Gov't;Cell Lineage;A pdf}, Number = {11}, Organization = {Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA. fkd2101\@columbia.edu}, Pages = {1127-34}, Pubmed = {14583753}, Title = {The glial identity of neural stem cells}, Uuid = {BD1FCAC8-A894-4D21-88A9-AF2E36777177}, Volume = {6}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14583753}} @article{Doetsch:1996, Abstract = {Cells in the brains of adult mammals continue to proliferate in the subventricular zone (SVZ) throughout the lateral wall of the lateral ventricle. Here we show, using whole mount dissections of this wall from adult mice, that the SVZ is organized as an extensive network of chains of neuronal precursors. These chains are immunopositive to the polysialylated form of NCAM, a molecule present at sites of plasticity, and TuJ1, an early neuronal marker. The majority of the chains are oriented along the rostrocaudal axis and many join the rostral migratory stream that terminates in the olfactory bulb. Using focal microinjections of DII and transplantation of SVZ cells carrying a neuron-specific reporter gene, we demonstrate that cells originating at different rostrocaudal levels of the SVZ migrate rostrally and reach the olfactory bulb where they differentiate into neurons. Our results reveal an extensive network of pathways for the tangential chain migration of neuronal precursors throughout the lateral wall of the lateral ventricle in the adult mammalian brain.}, Author = {Doetsch, F. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Brain/cytology/*physiology;02 Adult neurogenesis migration;Mammals;B-6a;*Nerve Net;Neurons/cytology/*physiology;Animal;Support, U.S. Gov't, P.H.S.;Cell Movement/*physiology;Mice}, Number = {25}, Organization = {Rockefeller University, New York, NY 10021, USA.}, Pages = {14895-900.}, Title = {Network of tangential pathways for neuronal migration in adult mammalian brain}, Uuid = {2DC83B8E-2080-46BA-981F-8176CE0F119E}, Volume = {93}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8962152}} @article{Doetsch:1999a, Abstract = {Neuronal precursors reside in the subventricular zone (SVZ) of adult mammals. This region is composed of a network of chains of migrating neuroblasts ensheathed by astrocytes and juxtaposed by clusters of immature precursors (type C cells). Here we show that after antimitotic treatment with cytosine-beta-D-arabinofuranoside, neuroblasts and type C cells are eliminated but some astrocytes remain. Remarkably, the SVZ network rapidly regenerates. Soon after cytosine-beta-D- arabinofuranoside treatment astrocytes divide. Two days later, type C cells reappear, followed at 4.5 days by migrating neuroblasts. By 10 days the SVZ network is fully regenerated, and the orientation and organization of chains of migrating neuroblasts resemble that of normal mice. This regeneration reveals an unexpected plasticity in the adult central nervous system and should provide a model system to study the early stages of neurogenesis in the adult brain.}, Author = {Doetsch, F. and Garcia-Verdugo, J. M. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Neural Cell Adhesion Molecules/analysis;02 Adult neurogenesis migration;Cytarabine/pharmacology;Cell Communication;Immunohistochemistry;Microscopy, Electron;B-10;Thymidine/metabolism;Brain/*cytology/drug effects/physiology;Regeneration;Glial Fibrillary Acidic Protein/analysis;Animal;Support, U.S. Gov't, P.H.S.;Mice;Male}, Number = {20}, Organization = {The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.}, Pages = {11619-24.}, Title = {Regeneration of a germinal layer in the adult mammalian brain}, Uuid = {7710F2B3-68D7-11DA-A4B6-000D9346EC2A}, Volume = {96}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10500226%20http://www.pnas.org/cgi/content/full/96/20/11619%20http://www.pnas.org/cgi/content/abstract/96/20/11619}} @article{Dogusan:2004, Abstract = {It has been hypothesized that B cell precursors that undergo programmed cell death due to nonproductive Ig gene rearrangements are cleared from the bone marrow by macrophages. However, a role for macrophages in this process is supported only by micrographs showing their association with apoptotic-appearing, B lineage cells. Functional data demonstrating phagocytosis of apoptotic, bone marrow lymphocytes by macrophages have not been presented, nor have receptors potentially involved in that process been identified. The data in this report demonstrate that macrophages isolated from murine bone marrow efficiently phagocytose apoptotic murine B lineage cells using multiple receptors that include CD14, integrins, class A scavenger receptor, and CD31 (PECAM-1). In addition, the results further reveal a new role for the hemopoietic microenvironment in B cell development in view of data demonstrating that murine bone marrow stromal cells are also capable of clearing apoptotic cells via an integrin-dependent mechanism.}, Author = {Dogusan, Zeynep and Montecino-Rodriguez, Encarnacion and Dorshkind, Kenneth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {Mice, Inbred BALB C;Phagocytosis;Animals;Cells, Cultured;Coculture Techniques;Macrophages;Integrins;Lymphoid Tissue;Apoptosis;B-Lymphocytes;11 Glia;Antigens, CD14;Antigens, CD31;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;Antigens, CD36;Mice;Stromal Cells}, Month = {4}, Nlm_Id = {2985117R}, Number = {8}, Organization = {Department of Pathology and Laboratory Medicine and the Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.}, Pages = {4717-23}, Pubmed = {15067047}, Title = {Macrophages and stromal cells phagocytose apoptotic bone marrow-derived B lineage cells}, Uuid = {FD895052-A713-44CC-AF32-FDFA20C6C7E6}, Volume = {172}, Year = {2004}} @article{Dolnikov:2003, Abstract = {In this study, the cell cycle modulation of retrovirus vector production and transduction was analysed. Retrovirus vector expression was found to be similar in all phases of the cell cycle and, in contrast to some other virus promoters shown previously to be upregulated by G(2)/M arrest, Moloney murine leukaemia virus LTR-driven expression was upregulated neither by G(2)/M growth arrest nor by G(1)/S growth arrest. In contrast, cultures enriched for S phase cells produced more infectious virions, apparently by modulation of stages consequent to provirus expression. In terms of retrovirus transduction, limitations appear to be slow progression through the cell cycle and short half-life of the virus. Synchronization of cells prior to mitosis can increase transduction efficiency. Cell cycle modulation can be used to modify retrovirus vector production and transduction and can allow short transduction periods. 0022-1317 Journal Article}, Author = {Dolnikov, A. and Wotherspoon, S. and Millington, M. and Symonds, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:20 -0400}, Journal = {J Gen Virol}, Keywords = {*Transduction, Genetic;*Genetic Vectors;*Cell Cycle;Human;EE, J pdf;Cell Line;08 Aberrant cell cycle;Retroviridae/*genetics/*growth &development;G2 Phase;Mitosis;Animals;Support, Non-U.S. Gov't;*Virus Cultivation;Virus Integration}, Number = {Pt 11}, Organization = {Department of Clinical Pharmacology and Toxicology, St Vincent's Hospital, Darlinghurst, NSW 2010, Australia.}, Pages = {3131-41}, Title = {Retrovirus vector production and transduction: modulation by the cell cycle}, Uuid = {B16F0C6C-CA28-4C3C-BDFB-1A089AA6B02F}, Volume = {84}, Year = {2003}, url = {papers/Dolnikov_JGenVirol2003.pdf}} @article{Domaradzka-Pytel:2000, Abstract = {The present study investigates the development of microglial and astroglial cells in the postnatal rat striatum, using immunohistochemical methods with panel antibodies that recognize macrophage antigens of unknown function--ED 1, complement type 3 receptor--OX-42 (for microglia) and glial fibrillary acidic protein (for astrocytes). On the day of birth, ED1/OX-42- immunoreactive microglial cells present in the striatum represent ameboid microglia. Between P0 and P10 we could observe the migration of ameboid microglial cells from neuroepithelial ventricular zone through internal and external capsules into the striatum. During the second postnatal week (P10, P14) a considerable decline of ameboid ED1-immunoreactive microglial cells and an increase of the number of OX-42 positive ramified cells was observed. At P21 only OX-42 positive ramified cells were observed in the whole striatum. On the day of birth, only a few GFAP-positive cells resembling radial glia were observed in the striatum. During the first postnatal week, the number of GFAP-positive cells increased significantly; they showed typical morphology of the astrocytes present in the adult animals. After P21 the final striatal population of astroglia was formed. Using Smart Source Parsing}, Author = {Domaradzka-Pytel, B. and Ludkiewicz, B. and Jagalska-Majewska, H. and Morys, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Folia Morphol}, Keywords = {Aging;Rats;Immunohistochemistry;Rats, Wistar;Animal;11 Glia;Animals, Newborn;Astrocytes/*cytology;Support, Non-U.S. Gov't;G;Corpus Striatum/cytology/*growth &development;Microglia/*cytology}, Number = {4}, Organization = {Department of Anatomy and Neurobiology, Medical University of Gdansk.}, Pages = {315-23}, Title = {Immunohistochemical study of microglial and astroglial cells during postnatal development of rat striatum}, Uuid = {012F55BF-F9B5-4783-BACE-8E937F1C6592}, Volume = {58}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11000888}} @article{Domaradzka-Pytel:1999, Abstract = {The distribution of microglia during the early stages of postnatal development in the rat was studied on rat brain from day of birth to postnatal day 90 (P90), using immunohistochemical methods with a panel of monoclonal antibodies that recognized the complement type 3 receptor (OX-42), macrophage antigen of unknown function (ED1), and the major histocompatibility complex (MHC) class I (OX-18) or class II (OX-6) antigens. Starting from the day of birth, ameboid microglia can be differentiated with positive immunoreactivity to OX-42, OX-18, and ED1. Labeled cells were localized mainly in the developing white matter. After P21, only positive reaction to OX-42 was present, and those cells had the typical morphology of the resting microglial cells that were located either in the white or grey matter. The changes in the appearance of different antigens are correlated with the morphological differentiation and transformation of ameboid microglial cells that are to become ramified microglia, present in the adult animals.}, Author = {Domaradzka-Pytel, B. and Ludkiewicz, B. and Mory\'{s}, J. and Wisniewski, H. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0021-8359}, Journal = {J Hirnforsch}, Keywords = {Aging;Cell Differentiation;Receptors, Complement;Telencephalon;Immunohistochemistry;Antibodies, Monoclonal;Histocompatibility Antigens Class II;Not relevant;Rats;Biological Markers;11 Glia;Microglia;Animals, Newborn;Rats, Wistar;Histocompatibility Antigens Class I;Animals;Support, Non-U.S. Gov't}, Medline = {20005253}, Nlm_Id = {0421521}, Number = {3}, Organization = {Department of Anatomy and Neurobiology, Medical University of Gda\'{n}sk, Poland.}, Pages = {283-91}, Pubmed = {10536861}, Title = {Expression and distribution of various antigens of developing microglial cells in the rat telencephalon}, Uuid = {F731D3F7-138E-4F6C-B3AD-29B1E784E551}, Volume = {39}, Year = {1999}, url = {papers/Domaradzka-Pytel_JHirnforsch1999.pdf}} @article{Dombeck:2007, Abstract = {We report a technique for two-photon fluorescence imaging with cellular resolution in awake, behaving mice with minimal motion artifact. The apparatus combines an upright, table-mounted two-photon microscope with a spherical treadmill consisting of a large, air-supported Styrofoam ball. Mice, with implanted cranial windows, are head restrained under the objective while their limbs rest on the ball's upper surface. Following adaptation to head restraint, mice maneuver on the spherical treadmill as their heads remain motionless. Image sequences demonstrate that running-associated brain motion is limited to approximately 2-5 microm. In addition, motion is predominantly in the focal plane, with little out-of-plane motion, making the application of a custom-designed Hidden-Markov-Model-based motion correction algorithm useful for postprocessing. Behaviorally correlated calcium transients from large neuronal and astrocytic populations were routinely measured, with an estimated motion-induced false positive error rate of <5\%.}, Author = {Dombeck, Daniel A. and Khabbaz, Anton N. and Collman, Forrest and Adelman, Thomas L. and Tank, David W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;research support, n.i.h., extramural;24 Pubmed search results 2008; 21 Calcium imaging;behavior;23 Technique;optogenetics}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Molecular Biology, Carl Icahn Labs, Princeton University, Princeton, NJ 08544, USA.}, Pages = {43-57}, Pii = {S0896-6273(07)00614-9}, Pubmed = {17920014}, Title = {Imaging large-scale neural activity with cellular resolution in awake, mobile mice}, Uuid = {3173C3FF-EE16-4634-973A-72864DED1FFD}, Volume = {56}, Year = {2007}, url = {papers/Dombeck_Neuron2007.pdf}, Bdsk-File-2 = {papers/Dombeck_Neuron2007.mov}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.08.003}} @article{Doms:1987, Abstract = {We have characterized the process by which the vesicular stomatitis virus (VSV) G protein acquires its final oligomeric structure using density-gradient centrifugation in mildly acidic sucrose gradients. The mature wild-type VSV G protein is a noncovalently associated trimer. Trimers are assembled from newly synthesized G monomers with a t1/2 of 6-8 min. To localize the site of trimerization and to correlate trimer formation with steps in transport between the endoplasmic reticulum (ER) and Golgi complex, we examined the kinetics of assembly of the temperature-sensitive mutant VSV strain, ts045. At the nonpermissive temperature (39 degrees C), ts045 G protein is not transported from the ER. The phenotypic defect that inhibited export from the ER at the nonpermissive temperature was found to be the accumulation of ts045 G protein in an aggregate. After being shifted to the permissive temperature (32 degrees C), the ts045 G protein aggregate rapidly dissociated (t1/2 less than 1 min) to monomeric G protein which subsequently trimerized with the same kinetics as the wild-type G protein. Only trimers were transported to the Golgi complex. Kinetic studies, as well as the finding that trimerization occurred under conditions which block ER to Golgi transport (at both 15 and 4 degrees C), showed that trimers were formed in the ER. Depletion of cellular ATP inhibited both the dissociation of the aggregated intermediate of ts045 G protein as well as the formation of stable trimers. The results indicate that oligomerization of G protein occurs in several steps, is sensitive to cellular ATP, and is required for transport from the ER.}, Author = {Doms, R. W. and Keller, D. S. and Helenius, A. and Balch, W. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {Adenosine Triphosphate;Macromolecular Substances;Research Support, Non-U.S. Gov't;Membrane Glycoproteins;Membrane Proteins;Kinetics;Cell Line;Research Support, U.S. Gov't, P.H.S.;Viral Matrix Proteins;Vesicular stomatitis-Indiana virus;Protein Processing, Post-Translational;15 Retrovirus mechanism;Animals;24 Pubmed search results 2008;Viral Envelope Proteins}, Medline = {88059229}, Month = {11}, Nlm_Id = {0375356}, Number = {5}, Organization = {Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510.}, Pages = {1957-69}, Pubmed = {2824524}, Title = {Role for adenosine triphosphate in regulating the assembly and transport of vesicular stomatitis virus G protein trimers}, Uuid = {481808F9-EE2C-11DA-8605-000D9346EC2A}, Volume = {105}, Year = {1987}} @article{Donaldson:1994, Abstract = {The distribution, cell tropism, and cytopathology in vivo of human immunodeficiency virus (HIV) was investigated in postmortem tissue samples from a series of HIV-infected individuals who died either of complications associated with AIDS or for unrelated reasons while they were asymptomatic. Proviral sequences were detected at a high copy number in lymphoid tissue of both presymptomatic patients and patients with AIDS, whereas significant infection of nonlymphoid tissue such as that from brains, spinal cords, and lungs were confined to those with AIDS. V3 loop sequences from both groups showed highly restricted sequence variability and a low overall positive charge of the encoded amino acid sequence compared with those of standard laboratory isolates of HIV type 1 (HIV-1). The low charge and the restriction in sequence variability were comparable to those observed with isolates showing a non-syncytium-inducing (NSI) and macrophage-tropic phenotype in vitro. All patients were either exclusively infected (six of seven cases) or predominantly infected (one case) with variants with a predicted NSI/macrophage-tropic phenotype, irrespective of the degree of disease progression. p24 antigen was detected by immunocytochemical staining of paraffin-fixed sections in the germinal centers within lymphoid tissue, although little or no antigen was found in areas of lymph node or spleen containing T lymphocytes from either presymptomatic patients or patients with AIDS. The predominant p24 antigen-expressing cells in the lungs and brains of the patients with AIDS were macrophages and microglia (in brains), frequently forming multinucleated giant cells (syncytia) even though the V3 loop sequences of these variants resembled those of NSI isolates in vitro. These studies indicate that lack of syncytium-forming ability in established T-cell lines does not necessarily predict syncytium-forming ability in primary target cells in vivo. Furthermore, variants of HIV with V3 sequences characteristic of NSI/macrophage-tropic isolates form the predominant population in a range of lymphoid and nonlymphoid tissues in vivo, even in patients with AIDS.}, Author = {Donaldson, Y. K. and Bell, J. E. and Holmes, E. C. and Hughes, E. S. and Brown, H. K. and Simmonds, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {T-Lymphocytes;Human;HIV-1;Humans;Base Sequence;Sequence Homology, Amino Acid;Macrophages;Comparative Study;Variation (Genetics);Acquired Immunodeficiency Syndrome;Sequence Alignment;Phylogeny;11 Glia;Genes, pol;Proviruses;HIV Infections;DNA Primers;Support, Non-U.S. Gov't;Amino Acid Sequence;Molecular Sequence Data;HIV Envelope Protein gp120;Research Support, Non-U.S. Gov't}, Medline = {94335116}, Month = {9}, Nlm_Id = {0113724}, Number = {9}, Organization = {Department of Medical Microbiology, University of Edinburgh, Medical School, United Kingdom.}, Pages = {5991-6005}, Pubmed = {7545945}, Title = {In vivo distribution and cytopathology of variants of human immunodeficiency virus type 1 showing restricted sequence variability in the V3 loop}, Uuid = {C0DBE78A-5A3F-4CD5-B329-1D42F72212A1}, Volume = {68}, Year = {1994}} @article{Donovan:2001, Abstract = {Pluripotent stem cells can be expanded seemingly indefinitely in culture, maintain a normal karyotype and have the potential to generate any cell type in the body. As such they represent an incredible resource for the repair of diseased or damaged tissues in our bodies. These cells also promise to open a new window into the embryonic development of our species. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Donovan, P. J. and Gearhart, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Nature}, Keywords = {F abstr;Embryo/cytology;10 Development;Models, Animal;Forecasting;Consumer Product Safety;Human;Cell Culture;Cell Line;*Stem Cells;*Cell Differentiation;Animals;Mice;Stem Cell Transplantation}, Number = {6859}, Organization = {Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. pdonovan\@lac.jci.tju.edu}, Pages = {92-7}, Pubmed = {11689953}, Title = {The end of the beginning for pluripotent stem cells}, Uuid = {8B0449FD-C616-4FE6-AB74-7B79951C09DF}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689953}} @article{Doron:2000, Abstract = {Auditory information from the posterior thalamus reaches the lateral nucleus of the amygdala (LA) by way of two pathways: a direct thalamo-amygdala projection and a polysynaptic thalamo-cortico-amygdala projection. However, the quantitative extent of thalamic neurons that project to the LA or to the auditory association cortex (AAC) is not known. Furthermore, the extent and topographical distribution of bifurcating cells that project to both LA and AAC are also unknown. Therefore, separate tracers were injected into LA and either into all of AAC or within discrete regions of AAC, such as temporal areas TE3 or perirhinal cortex (PRh), and quantitative analyses were performed on labeling within the subregions of the auditory thalamus in rats. Following LA injections, retrogradely labeled cells were most numerous in the posterior intralaminar nucleus (PIN; 48.0\%of all labeled thalamic cells), whereas labeled cells following injections of the entire AAC were most numerous in the dorsal division of the medial geniculate nucleus (MGd; 32.9\%of all labeled thalamic cells). Following AAC injections localized to only TE3, the MGd again had the majority of labeled cells (35.9\%), whereas following AAC injections localized to PRh, the PIN had the most labeled cells (32.8\%). Double-labeled cells were found in all the thalamic regions studied and were most commonly observed in the PIN (43.7\%of all double-labeled cells following injections into LA and throughout the AAC). The percentage of double-labeled cells as a proportion of either LA-projecting or AAC-projecting cells varied among the thalamic nuclei studied, ranging from 2.9\%up to 42.4\%. The topographic distribution of double-labeled cells in the thalamic nuclei resembled that of single-labeled cells following LA injections more than single-labeled cells following AAC injection. These findings suggest that double-labeled cells contribute substantially to many of the direct thalamo-amygdala and indirect thalamo-AAC-amygdala projections. Among other functions, these bifurcating cells may help regulate the processing of input to the LA arriving from these two pathways to allow for certain types of plasticity in the LA during fear conditioning.}, Author = {Doron, N. N. and Ledoux, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Auditory Cortex;Conditioning (Psychology);Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;Posterior Thalamic Nuclei;Rats;Neural Pathways;Research Support, U.S. Gov't, P.H.S.;Cell Count;Fear;Amygdala;Injections;Male;Animals;Neurons;24 Pubmed search results 2008}, Medline = {20413206}, Month = {9}, Nlm_Id = {0406041}, Number = {2}, Organization = {W.M. Keck Laboratories of Neurobiology, Center for Neural Science, New York University, New York, New York 10003, USA.}, Pages = {257-74}, Pii = {10.1002/1096-9861(20000918)425:2<257::AID-CNE8>3.0.CO;2-Y}, Pubmed = {10954844}, Title = {Cells in the posterior thalamus project to both amygdala and temporal cortex: a quantitative retrograde double-labeling study in the rat}, Uuid = {520646BE-FA56-4682-B04C-C24AB0529219}, Volume = {425}, Year = {2000}} @article{Dorus:2004, Abstract = {Human evolution is characterized by a dramatic increase in brain size and complexity. To probe its genetic basis, we examined the evolution of genes involved in diverse aspects of nervous system biology. We found that these genes display significantly higher rates of protein evolution in primates than in rodents. Importantly, this trend is most pronounced for the subset of genes implicated in nervous system development. Moreover, within primates, the acceleration of protein evolution is most prominent in the lineage leading from ancestral primates to humans. Thus, the remarkable phenotypic evolution of the human nervous system has a salient molecular correlate, i.e., accelerated evolution of the underlying genes, particularly those linked to nervous system development. In addition to uncovering broad evolutionary trends, our study also identified many candidate genes-most of which are implicated in regulating brain size and behavior-that might have played important roles in the evolution of the human brain.}, Author = {Dorus, Steve and Vallender, Eric J. and Evans, Patrick D. and Anderson, Jeffrey R. and Gilbert, Sandra L. and Mahowald, Michael and Wyckoff, Gerald J. and Malcom, Christine M. and Lahn, Bruce T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {10 Development;19 Neocortical evolution}, Month = {12}, Nlm_Id = {0413066}, Number = {7}, Organization = {Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637 USA.}, Pages = {1027-40}, Pii = {S0092867404011432}, Pubmed = {15620360}, Title = {Accelerated Evolution of Nervous System Genes in the Origin of Homo sapiens}, Uuid = {C211CCDA-AD83-42DB-A262-9B8DEE5B112C}, Volume = {119}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.11.040}} @article{Doucette:1993, Abstract = {There are two morphologically distinct types of glial cells (i.e., ensheathing cells and astrocytes) in the nerve fiber layer (NFL) of the adult mammalian olfactory bulb. Ensheathing cells provide ensheathment for olfactory axons, whereas astrocytes occupy the interfascicular spaces of the olfactory NFL. During embryonic development, however, only one type of glial cell is found in this layer of the olfactory bulb, namely, the ensheathing cell. Even though ensheathing cells take up residence within the CNS, they are actually derived from the olfactory placode. Far less is known about the developmental origin of interfascicular astrocytes, which arise either from the glial progenitor cells that give rise to ensheathing cells or from astrocyte precursor cells that migrate into the NFL from deeper layers of the bulb primordium. In the present study, enriched populations of ensheathing cells were grown in vitro in media known to promote the growth and differentiation of astrocytes to determine whether ensheathing cell progenitors could differentiate into astrocytes. These media failed to induce the appearance of astrocytes in the ensheathing cell cultures. It was concluded that the astrocytes of the NFL most likely arise from progenitor cells that migrate into this layer from deeper parts of the developing bulb.}, Author = {Doucette, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci Res}, Keywords = {Pregnancy;Rats;Phenotype;Neuroglia/*physiology;Olfactory Bulb/*cytology/embryology;Female;Animal;Astrocytes/physiology;Rats, Wistar;G abstr;11 Glia;Stem Cells/*physiology;Support, Non-U.S. Gov't;Mice;Animals, Newborn/physiology;Immunohistochemistry;Cell Differentiation/physiology;Nerve Fibers/*physiology;Culture Media}, Number = {3}, Organization = {Department of Anatomy, College of Medicine, University of Saskatchewan, Saskatoon, Canada.}, Pages = {274-87.}, Title = {Glial progenitor cells of the nerve fiber layer of the olfactory bulb: effect of astrocyte growth media}, Uuid = {4F6013D5-580C-4F9F-940F-DB6CF96525CE}, Volume = {35}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8350389}} @article{Douen:2004, Abstract = {During embryogenesis, transient expression of nestin in proliferating neuroepithelial stem cells signals the commitment of progenitor cells to differentiate. Although adult mammalian brain contains very little nestin, significant upregulation of nestin has been reported following cerebral injury, leading to speculation that nestin may be involved in brain repair. In this study, we assessed the temporal profile of nestin expression following ablation injury of the sensory barrel cortex and investigated the influence of contralateral whisker stimulation on nestin expression. Since the adult mammalian brain contains proliferating neuronal progenitor cells that can be labeled with bromodeoxyuridine (BrdU), we also determined the association of nestin reexpression with BrdU-labeled cells. Nestin reexpression was detected predominantly in the ipsilateral cortex 3 days post-ablation. There was no significant nestin upregulation in the subcortical region. Nestin reexpression was most marked surrounding the lesion, but also extended throughout the entire lateral cortex. Nestin in the ipsilateral cortex subsided by day 7, although perilesional nestin expression was still apparent 28 days post-injury. Western blot analysis of nestin expression 3 days post-ablation confirmed a significant two-fold increase in nestin expression (p<0.05). Double immunofluorescence labeling demonstrated that the majority of nestin expression occurred in astrocytes. We were unable to detect any colocalization with neuronal makers. However, BrdU-labeled cells, which were readily detected in the subventricular zone prior to injury, were readily detected in the perilesional area 3 days post-ablation, concomitant with nestin in this area. Confocal microscopy detected several BrdU-positive cells expressing nestin. Taken together, the data support a potential role for nestin reexpression in brain repair.}, Author = {Douen, A. G. and Dong, Li and Vanance, S. and Munger, R. and Hogan, M. J. and Thompson, C. S. and Hakim, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Animals;Rats;Fluorescent Antibody Technique;Microscopy, Confocal;Indicators and Reagents;Vibrissae;Rats, Wistar;Physical Stimulation;Motor Cortex;Deoxyglucose;Antimetabolites;Nerve Regeneration;Male;Brain Chemistry;Blotting, Western;Intermediate Filament Proteins;Cerebral Cortex;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine;Nerve Tissue Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Month = {5}, Nlm_Id = {0045503}, Number = {2}, Organization = {Trillium Medical Centre, Mississauga, Ontario, Canada.}, Pages = {139-46}, Pii = {S0006899304002331}, Pubmed = {15145750}, Title = {Regulation of nestin expression after cortical ablation in adult rat brain}, Uuid = {325FE1FE-40BE-4EEA-8094-DBED17895ECF}, Volume = {1008}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainres.2003.08.070}} @article{Doyle:2001, Abstract = {The intermediate filament protein nestin has been widely used as a marker for proliferating neural progenitor cells in the nervous system. The mammalian olfactory neuroepithelium is a region of the nervous system that robustly supports ongoing neurogenesis, yet where nestin has not been reported to mark proliferating progenitors. Using immunohistochemistry, we examined nestin expression in the mature olfactory neuroepithelium and found it to be tightly restricted to the basal compartment where the olfactory neuronal progenitor cell population resides. The pattern of nestin immunoreactivity was consistent with expression by the endfeet and inferior processes of sustentacular cells rather than basal cells. Using a bank of defined antibody markers, we confirmed nestin's pattern of distribution to be different from that of cytokeratin, vimentin, GBC-1, GAP43, and carnosine. It was highly similar to the pattern of SUS-4 immunoreactivity in the basal region of the neuroepithelium. Following surgical bulbectomy, nestin expression was up-regulated and became evident in the cell bodies of sustentacular cells situated more apically in the neuroepithelium. We have shown nestin to be present in the basal region of the adult olfactory neuroepithelium in the zone that supports ongoing neurogenesis in the adult, but its expression is restricted to the inferior parts of sustentacular cells rather than the neuronal progenitor cells. Nestin may play a potential role in the migration of recently proliferated olfactory neurons on the scaffolding of sustentacular cells in a manner analogous to its proposed role in radial glia during embryonic development of the central nervous system. Copyright 2001 Wiley-Liss, Inc. eng Journal Article}, Author = {Doyle, K. L. and Khan, M. and Cunningham, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Journal = {J Comp Neurol}, Keywords = {02 Adult neurogenesis migration;03 Adult neurogenesis progenitor source;BB abstr}, Number = {2}, Organization = {Neurobiology Program, The Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.}, Pages = {186-95.}, Title = {Expression of the intermediate filament protein nestin by sustentacular cells in mature olfactory neuroepithelium}, Uuid = {45CB9D4B-9A66-4D5F-9FD0-A31B088402E2}, Volume = {437}, Year = {2001}} @article{Dorr:2002, Abstract = {Apoptosis mediated by members of the tumor necrosis factor (TNF)-nerve growth factor superfamily plays a crucial role in the interaction of the nervous and the immune system. On the one hand, it is involved in the defense mechanisms of the brain, the immune privilege. On the other hand, it is involved in the induction of glial-neuronal cell death in neuroinflammatory diseases. Here, we show that in contrast to the other known death ligands, TNF-related apoptosis-inducing ligand (TRAIL) is not constitutively expressed in the human brain, whereas both apoptosis-mediating and apoptosis-blocking TRAIL receptors are found on neurons, astrocytes, and oligodendrocytes. Thus, the brain differs from other immune-privileged organs, such as the placenta, with the TRAIL receptor-TRAIL system not being part of the immune privilege of the brain. Conversely, this death receptor-ligand system might well play an important role in T cell-mediated autoimmune diseases of the CNS such as multiple sclerosis.}, Author = {D{\"o}rr, Jan and Bechmann, Ingo and Waiczies, Sonia and Aktas, Orhan and Walczak, Henning and Krammer, Peter H. and Nitsch, Robert and Zipp, Frauke}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Epilepsy;Brain Chemistry;Membrane Glycoproteins;Research Support, Non-U.S. Gov't;Reverse Transcriptase Polymerase Chain Reaction;Immunohistochemistry;Cell Line;Apoptosis;Placenta;Tumor Necrosis Factor-alpha;Antibody Specificity;11 Glia;Receptors, Tumor Necrosis Factor;RNA, Messenger;Humans;Blotting, Western;Brain}, Medline = {21839207}, Month = {2}, Nlm_Id = {8102140}, Number = {4}, Organization = {Department of Neurology, Division of Neuroimmunology, Charit{\'e} Neuroscience Research Center, 10098 Berlin, Germany.}, Pages = {RC209}, Pii = {20026087}, Pubmed = {11844843}, Title = {Lack of tumor necrosis factor-related apoptosis-inducing ligand but presence of its receptors in the human brain}, Uuid = {4051B298-6087-40FD-8068-32DBC19A4B0E}, Volume = {22}, Year = {2002}} @article{Dragoi:2001, Abstract = {Cortical areas are generally assumed to be uniform in their capacity for adaptive changes or plasticity. Here we demonstrate, however, that neurons in the cat striate cortex (V1) show pronounced adaptation-induced short-term plasticity of orientation tuning primarily at specific foci. V1 neurons are clustered according to their orientation preference in iso-orientation domains that converge at singularities or pinwheel centres. Although neurons in pinwheel centres have similar orientation tuning and responses to those in iso-orientation domains, we find that they differ markedly in their capacity for adaptive changes. Adaptation with an oriented drifting grating stimulus alters responses of neurons located at and near pinwheel centres to a broad range of orientations, causing repulsive shifts in orientation preference and changes in response magnitude. In contrast, neurons located in iso-orientation domains show minimal changes in their tuning properties after adaptation. The anisotropy of adaptation-induced orientation plasticity is probably mediated by inhomogeneities in local intracortical interactions that are overlaid on the map of orientation preference in V1.}, Author = {Dragoi, V. and Rivadulla, C. and Sur, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Visual Cortex;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Cats;Neuronal Plasticity;research support, non-u.s. gov't ;Electrophysiology;Animals;24 Pubmed search results 2008;Neurons}, Month = {5}, Nlm_Id = {0410462}, Number = {6833}, Organization = {Department of Brain and Cognitive Sciences and Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. vdragoi\@ai.mit.edu}, Pages = {80-6}, Pii = {35075070}, Pubmed = {11333981}, Title = {Foci of orientation plasticity in visual cortex}, Uuid = {B93A5B08-D0CA-4637-ADC0-29916ADBD186}, Volume = {411}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35075070}} @article{Draguhn:1998, Abstract = {Coherent oscillations, in which ensembles of neurons fire in a repeated and synchronous manner, are thought to be important in higher brain functions. In the hippocampus, these discharges are categorized according to their frequency as theta (4-10Hz), gamma (20-80 Hz) and high-frequency (approximately 200 Hz) discharges, and they occur in relation to different behavioural states. The synaptic bases of theta and gamma rhythms have been extensively studied but the cellular bases for high-frequency oscillations are not understood. Here we report that high-frequency network oscillations are present in rat brain slices in vitro, occurring as a brief series of repetitive population spikes at 150-200 Hz in all hippocampal principal cell layers. Moreover, this synchronous activity is not mediated through the more commonly studied modes of chemical synaptic transmission, but is in fact a result of direct electrotonic coupling of neurons, most likely through gap-junctional connections. Thus high-frequency oscillations synchronize the activity of electrically coupled subsets of principal neurons within the well-documented synaptic network of the hippocampus.}, Author = {Draguhn, A. and Traub, R. D. and Schmitz, D. and Jefferys, J. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:44 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Excitatory Amino Acid Antagonists;Animals;Rats;Female;Hippocampus;Rats, Wistar;Calcium;Gap Junctions;research support, non-u.s. gov't;Bicuculline;Male;Action Potentials;21 Neurophysiology;Neurons;GABA Antagonists;21 Gap junctions;Oscillometry;in vitro}, Month = {7}, Nlm_Id = {0410462}, Number = {6689}, Organization = {Department of Physiology, The Medical School, University of Birmingham, UK. draguhn\@rz.charite.hu-berlin.de}, Pages = {189-92}, Pubmed = {9671303}, Title = {Electrical coupling underlies high-frequency oscillations in the hippocampus in vitro}, Uuid = {7668D648-3BC8-442A-9FC6-15111DF1BDDF}, Volume = {394}, Year = {1998}, url = {papers/Draguhn_Nature1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/28184}} @article{Drapeau:2003, Abstract = {Neurogenesis occurs within the adult dentate gyrus of the hippocampal formation and it has been proposed that the newly born neurons, recruited into the preexistent neuronal circuits, might be involved in hippocampal-dependent learning processes. Age-dependent spatial memory impairments have been related to an alteration in hippocampal plasticity. The aim of the current study was to examine whether cognitive functions in aged rats are quantitatively correlated with hippocampal neurogenesis. To this end, we took advantage of the existence of spontaneous individual differences observed in aged subjects in a hippocampal-dependent task, the water maze. We expected that the spatial memory capabilities of aged rats would be related to the levels of hippocampal neurogenesis. Old rats were trained in the water maze, and, 3 weeks after training, rats were injected with 5-bromo-2'-deoxyuridine (BrdUrd, 50 or 150 mg/kg) to label dividing cells. Cell proliferation was examined one day after the last BrdUrd injection, whereas cell survival and differentiation were determined 3 weeks later. It is shown that a quantitative relationship exists between learning and the number of newly generated neurons. Animals with preserved spatial memory, i.e., the aged-unimpaired rats, exhibited a higher level of cell proliferation and a higher number of new neurons in comparison with rats with spatial memory impairments, i.e., the aged-impaired rats. In conclusion, the extent of memory dysfunction in aged rats is quantitatively related to the hippocampal neurogenesis. These data reinforce the assumption that neurogenesis is involved in memory processes and aged-related cognitive alterations. 0027-8424 Journal Article}, Author = {Drapeau, E. and Mayo, W. and Aurousseau, C. and Le Moal, M. and Piazza, P. V. and Abrous, D. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;A pdf}, Number = {24}, Organization = {Institut National de la Santa et de la Recherche Medicale Unite 588, Domaine de Carreire, Rue Camille Saint Saens, University of Bordeaux II, 33077 Bordeaux Cedex, France.}, Pages = {14385-90}, Pubmed = {14614143}, Title = {Spatial memory performances of aged rats in the water maze predict levels of hippocampal neurogenesis}, Uuid = {2A4E97E2-B7CC-4533-9F1C-24204593AD11}, Volume = {100}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14614143}} @article{Drescher:2002, Abstract = {Eph receptor tyrosine kinases and ephrins have been identified in organisms ranging from sponges to flies and worms to chick, mice and humans, thus allowing their function to be approached also from an evolutionary perspective. The structural analysis of Eph/ephrin crystals is providing hints for the existence of Eph and ephrin folds in plants and suggests a mechanism for triggering bi-directional signalling.}, Author = {Drescher, Uwe}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0959-437X}, Journal = {Curr Opin Genet Dev}, Keywords = {Retina;Receptors, Eph Family;10 Development;Protein Structure, Tertiary;Phylogeny;Evolution, Molecular;Multigene Family;10 circuit formation;Ephrins;Animals;Superior Colliculi;24 Pubmed search results 2008;review}, Month = {8}, Nlm_Id = {9111375}, Number = {4}, Organization = {MRC Centre for Developmental Neurobiology, King's College London, New Hunt's House, London, UK. uwe.drescher\@kcl.ac.uk}, Pages = {397-402}, Pii = {S0959437X02003167}, Pubmed = {12100883}, Title = {Eph family functions from an evolutionary perspective}, Uuid = {F8A5D055-88E9-4301-A1E9-1AB8FE2A468F}, Volume = {12}, Year = {2002}, url = {papers/Drescher_CurrOpinGenetDev2002.pdf}} @article{Dromard:2006, Abstract = {Neural stem cells cultured with FGF2/EGF generate clonal expansions called neurospheres (NS) which are widely used for therapy in animal models. However, their cellular composition is still poorly defined. Here, we report that NS derived from several embryonic and adult central nervous system (CNS) regions are mainly composed of remarkable cells coexpressing radial glia markers (BLBP, RC2, GLAST), oligodendrogenic/neurogenic factors (Mash1, Olig2, Nkx2.2) and markers which in vivo are typical of the oligodendrocyte lineage (NG2, A2B5, PDGFRalpha). On NS differentiation, the latter remain mostly expressed in neurons, together with Olig2 and Mash1. Using cytometry, we show that in growing NS the small population of multipotential self-renewing NS-forming cells are A2B5(+) and NG2(+). Additionally, we demonstrate that these NS-forming cells in the embryonic spinal cord were initially NG2- and rapidly acquired NG2 in vitro. NG2 and Olig2 were found to be rapidly induced by cell culture conditions in spinal cord neural precursor cells. Olig2 expression was also induced in astrocytes and embryonic peripheral nervous system (PNS) cells in culture following EGF/FGF treatment. These data provide new evidence for profound phenotypic modifications in CNS and PNS neural precursor cells induced by culture conditions.}, Author = {Dromard, and Bartolami, and Deleyrolle, and Takebayashi, and Ripoll, and Simonneau, and Prome, and Puech, and Tran Van Ba, and Duperray, and Valmier, and Privat, and Hugnot,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9304532}, Organization = {INSERM U583, Physiopathologie et Th{\'e}rapie des d{\'e}ficits sensoriels et moteurs, Institut des Neurosciences de Montpellier, H\^{o}pital St ELOI, Montpellier, France.}, Pii = {2005-0556}, Pubmed = {17053213}, Title = {NG2 and olig2 expression provides evidence for phenotypic deregulation of cultured CNS and PNS neural precursor cells}, Uuid = {7569E901-515A-49F1-A24C-3065E34418DE}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1634/stemcells.2005-0556}} @article{Du:1995, Abstract = {We recently described a pronounced neuronal loss in layer III of the entorhinal cortex (EC) in patients with intractable temporal lobe epilepsy (Du et al., 1993a). To explore the pathophysiology underlying this distinct neuropathology, we examined the EC in three established rat models of epilepsy using Nissl staining and parvalbumin immunohistochemistry. Adult male rats were either electrically stimulated in the ventral hippocampus for 90 min or injected with kainic acid or lithium/pilocarpine. Animals were observed for behavioral changes for up to 6 hr and were killed 24 hr or 4 weeks after the experimental treatments. At 24 hr, all animals that had exhibited a bout of acute status epilepticus showed a consistent pattern of neuronal loss in the EC in Nissl-stained sections. Neurodegeneration was most pronounced in layer III of the medial Ec at all dorsoventral levels. A few surviving neurons were frequently present in the lesioned area. An identical pattern of nerve cell loss was also seen in the EC of rats killed 4 weeks following the treatments. This lesion was completely prevented by an injection of diazepam and pentobarbital, given 1 hr after kainic acid administration. Immunohistochemistry demonstrated a relative resistance of parvalbumin-positive neurons in layer III of the medial EC. Taken together, these experiments indicate that prolonged seizures cause a preferential neuronal loss in layer III of the medial EC and that this lesion may be related to a pathological elevation of intracellular calcium ion concentrations.}, Author = {Du, F. and Eid, T. and Lothman, E. W. and Kohler, C. and Schwarcz, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {J Neurosci}, Keywords = {Pilocarpine;Electric Stimulation;Rats;07 Excitotoxicity Apoptosis;Status Epilepticus/chemically induced/etiology/pathology;E-4;Animal;Rats, Sprague-Dawley;Kainic Acid;Behavior, Animal;Lithium;Male;Neurons/*pathology;Support, Non-U.S. Gov't;Entorhinal Cortex/*pathology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Cell Death;Epilepsy, Temporal Lobe/*pathology}, Number = {10}, Organization = {Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore 21228, USA.}, Pages = {6301-13.}, Title = {Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy}, Uuid = {978F444F-4110-44CB-BFFE-8CEF3676A4E3}, Volume = {15}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7472396}} @article{Duan:2007, Abstract = {Adult neurogenesis occurs throughout life in discrete regions of the adult mammalian brain. Little is known about the mechanism governing the sequential developmental process that leads to integration of new neurons from adult neural stem cells into the existing circuitry. Here, we investigated roles of Disrupted-In-Schizophrenia 1 (DISC1), a schizophrenia susceptibility gene, in adult hippocampal neurogenesis. Unexpectedly, downregulation of DISC1 leads to accelerated neuronal integration, resulting in aberrant morphological development and mispositioning of new dentate granule cells in a cell-autonomous fashion. Functionally, newborn neurons with DISC1 knockdown exhibit enhanced excitability and accelerated dendritic development and synapse formation. Furthermore, DISC1 cooperates with its binding partner NDEL1 in regulating adult neurogenesis. Taken together, our study identifies DISC1 as a key regulator that orchestrates the tempo of functional neuronal integration in the adult brain and demonstrates essential roles of a susceptibility gene for major mental illness in neuronal development, including adult neurogenesis.}, Author = {Duan, Xin and Chang, Jay H. and Ge, Shaoyu and Faulkner, Regina L. and Kim, Ju Young and Kitabatake, Yasuji and Liu, Xiao-bo B. and Yang, Chih-Hao H. and Jordan, J. Dedrick and Ma, Dengke K. and Liu, Cindy Y. and Ganesan, Sundar and Cheng, Hwai-Jong J. and Ming, Guo-li L. and Lu, Bai and Song, Hongjun}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Cell Differentiation;Genetic Vectors;24 Pubmed search results 2008;Genotype;Animals;Hippocampus;Synaptic Transmission;Cell Movement;Morphogenesis;Phenotype;research support, n.i.h., extramural;Synapses;Mice, Inbred C57BL;Dendrites;Carrier Proteins;Schizophrenia;Retroviridae;Action Potentials;Time Factors;RNA, Small Interfering;Cell Lineage;Cell Size;research support, non-u.s. gov't;Cell Proliferation;Recombinant Fusion Proteins;Mice;Neurons;Stem Cells;Nerve Tissue Proteins;RNA Interference;Dentate Gyrus}, Month = {9}, Nlm_Id = {0413066}, Number = {6}, Organization = {Institute for Cell Engineering, Johns Hopkins University School of Medicine, 733 N. Broadway, Baltimore, MD 21205, USA.}, Pages = {1146-58}, Pii = {S0092-8674(07)00897-5}, Pubmed = {17825401}, Title = {Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain}, Uuid = {1F52DD1A-ADD4-4B49-942A-F3266E3D31CE}, Volume = {130}, Year = {2007}, url = {papers/Duan_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2007.07.010}} @article{Duan:2005, Abstract = {A major problem for neuroscience has been to find a means to achieve reliable regeneration of synaptic connections following injury to the adult CNS. This problem has been solved by the leech, where identified neurons reconnect precisely with their usual targets following axotomy, re-establishing in the adult the connections formed during embryonic development. It cannot be assumed that once axons regenerate specific synapses, function will be restored. Recent work on the leech has shown following regeneration of the synapse between S-interneurons, which are required for sensitization of reflexive shortening, a form of non-associative learning, the capacity for sensitization is delayed. The steps in repair of synaptic connections in the leech are reviewed, with the aim of understanding general mechanisms that promote successful repair. New results are presented regarding the signals that regulate microglial migration to lesions, a first step in the repair process. In particular, microglia up to 900 microm from the lesion respond within minutes by moving rapidly toward the injury, controlled in part by nitric oxide (NO), which is generated immediately at the lesion and acts via a soluble guanylate cyclase (sGC). The cGMP produced remains elevated for hours after injury. The relationship of microglial migration to axon outgrowth is discussed.}, Author = {Duan, Yuanli and Panoff, Joseph and Burrell, Brian D. and Sahley, Christie L. and Muller, Kenneth J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0272-4340}, Journal = {Cell Mol Neurobiol}, Keywords = {Alpha;11 Glia}, Medline = {102378122}, Month = {3}, Nlm_Id = {8200709}, Number = {2}, Organization = {Department of Physiology & Biophysics, University of Miami School of Medicine, Miami, Florida 33136, USA.}, Pages = {441-50}, Pubmed = {16047551}, Title = {Repair and regeneration of functional synaptic connections: cellular and molecular interactions in the leech}, Uuid = {184D781B-C650-4D31-942A-3B8BC33BBA9E}, Volume = {25}, Year = {2005}, url = {papers/Duan_CellMolNeurobiol2005.pdf}} @article{Dubeau:1995, Abstract = {Grey matter heterotopias, demonstrated by MRI, may present with a broad spectrum of clinical severity. We have studied 33 patients with periventricular nodular heterotopias (PNH); 19 (58\%) had unilateral and 14 (42\%) bilateral lesions. Thirteen of the 19 patients (68\%) with unilateral subependymal nodules of grey matter had, in addition, unilateral focal subcortical heterotopias (SNH), comprising 39\%of the entire group. Most had normal intellectual and motor function but some presented with mild mental retardation and neurological deficits. Recurrent seizures were described in 82\%, mainly partial attacks with temporo-parieto-occipital auras. Nodular heterotopias led to unilateral or bilateral independent temporal epileptic discharges in 47\%of epileptic patients with PNH alone and in 61\%of those who had SNH in addition. Extratemporal or multilobar, unilateral or bilateral interictal spiking was present in 10 other patients (36\%). Two first degree relatives of patients with seizures were affected but had no seizures, three were investigated for other apparently unrelated neurological symptoms: memory impairment, vertigo or transient ischaemic attacks in one person each. Contiguous ovoid nodules of grey matter, symmetrically lining both lateral ventricles, were described in nine patients. Seven of them were female, including four with familial incidence of PNH. Such lesions may explain the familial occurrence of epilepsy in some families. Seven patients underwent anterior temporal resection: two patients with unilateral subependymal and focal subcortical heterotopias were seizure free or significantly improved. Four patients, three with PNH alone and one with additional subcortical nodules, did not improve significantly after surgery. The remaining patient was followed for less than 6 months.}, Author = {Dubeau, F. and Tampieri, D. and Lee, N. and Andermann, E. and Carpenter, S. and Leblanc, R. and Olivier, A. and Radtke, R. and Villemure, J. G. and Andermann, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0006-8950}, Journal = {Brain}, Keywords = {10 Development;Magnetic Resonance Imaging;Child, Preschool;Humans;Middle Aged;Female;Epilepsy;Child;Brain Diseases;Male;Cerebral Ventricles;10 genetics malformation;Cerebral Cortex;Adult;24 Pubmed search results 2008;Choristoma;Data Interpretation, Statistical;Electroencephalography;Adolescent}, Month = {10}, Nlm_Id = {0372537}, Organization = {Department of Neurology and Neurosurgery, Montreal Neurological Hospital, Canada.}, Pages = {1273-87}, Pubmed = {7496786}, Title = {Periventricular and subcortical nodular heterotopia. A study of 33 patients}, Uuid = {19F63C25-2E09-464A-86A8-5EEDB06ECE0D}, Volume = {118 ( Pt 5)}, Year = {1995}} @article{Dubois-Dalcq:2005, Abstract = {Recent studies on adult neural stem cells and the developmental biology of myelination have generated the expectation that neural precursors can repair the damaged central nervous system of multiple sclerosis patients where the endogenous remyelination process has failed. As a result, many laboratories are engaged in translational studies in which the goal is to design ways to promote remyelination and repair. Here we raise issues highlighted by prior experimental and human work that should be considered lest these studies become "lost in translation."}, Author = {Dubois-Dalcq, Monique and Ffrench-Constant, Charles and Franklin, Robin J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Models, Biological;24 Pubmed search results 2008;Multiple Sclerosis;Central Nervous System;Myelin Sheath;Regeneration;Tissue Therapy;Animals;Oligodendroglia;Disease Models, Animal;review;Humans}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. dalcqm\@mail.nih.gov}, Pages = {9-12}, Pii = {S0896-6273(05)00770-1}, Pubmed = {16202704}, Title = {Enhancing central nervous system remyelination in multiple sclerosis}, Uuid = {F3A0CD50-409A-4704-97A3-079A981BDE00}, Volume = {48}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.09.004}} @article{Duch:2004, Abstract = {Insect metamorphosis is a compelling example for dendritic and synaptic remodeling as larval and adult behaviors place distinct demands on the CNS. During the metamorphosis of the moth, Manduca sexta, many larval motoneurons are remodeled to serve a new function in the adult. During late larval life, steroid hormones trigger axonal and dendritic regression as well as larval synapse elimination. These regressive events are accompanied by stereotypical changes in motor behavior during the so-called wandering stages. Both normally occurring changes in dendritic shape and in motor output have previously been analyzed quantitatively for the individually identified motoneuron MN5. This study tested whether activity affected steroid-induced dendritic regression and synapse disassembly in MN5 by means of chronically implanted extracellular electrodes. Stimulating MN5 in vivo in intact, normally developing animals during a developmental period when it usually shows no activity significantly slowed the regression of high-order dendrites. Both physiological and anatomical analysis demonstrated that reduced dendritic regression was accompanied by a significant reduction in larval synapse disassembly. Therefore, steroid-induced alterations of dendritic shape and synaptic connectivity are modified by activity-dependent mechanisms. This interaction might be a common mechanism for rapid adjustments of rigid, inflexible, hormonal programs.}, Author = {Duch, Carsten and Mentel, Tim}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;10 Structural plasticity;Beta}, Month = {11}, Nlm_Id = {8102140}, Number = {44}, Organization = {Institute of Biology and Neurobiology, Free University Berlin, 14195 Berlin, Germany.}, Pages = {9826-37}, Pii = {24/44/9826}, Pubmed = {15525767}, Title = {Activity Affects Dendritic Shape and Synapse Elimination during Steroid Controlled Dendritic Retraction in Manduca sexta}, Uuid = {31A302DE-E130-430A-9CF2-D6C9BBF8A88E}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3189-04.2004}} @article{Duchaine:2001, Abstract = {The human brain is a set of computational machines, each of which was designed by natural selection to solve adaptive problems faced by our hunter-gatherer ancestors. These machines are adaptive specializations: systems equipped with design features that are organized such that they solve an ancestral problem reliably, economically and efficiently. The search for functionally specialized computational adaptations has now begun in earnest. A host of specialized systems have recently been found, including ones designed for sexual motivation, social inference, judgment under uncertainty and conditioning, as well as content-rich systems for visual recognition and knowledge acquisition.}, Author = {Duchaine, B. and Cosmides, L. and Tooby, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {research support, non-u.s. gov't;Visual Perception;21 Neurophysiology;Adaptation, Psychological;Recognition (Psychology);Motivation;Evolution;Animals;Brain;Humans;review;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9111376}, Number = {2}, Organization = {Department of Psychology, University of California, Santa Barbara, CA 93106, USA. duchaine\@psych.ucsb.edu}, Pages = {225-30}, Pii = {S0959-4388(00)00201-4}, Pubmed = {11301244}, Title = {Evolutionary psychology and the brain}, Uuid = {307D1B27-DDB5-40A5-9F7D-5BB2D438FA9B}, Volume = {11}, Year = {2001}, url = {papers/Duchaine_CurrOpinNeurobiol2001.pdf}} @article{Duchaine:2006, Abstract = {Developmental prosopagnosia is characterized by severely impaired face recognition. Individuals with this disorder, which often runs in families, have no history of brain damage and intact early visual processing systems. Recent research has also demonstrated that many developmental prosopagnosics have normal or relatively good object recognition, indicating that their impairments are not the result of deficits to a unitary visual recognition mechanism. To investigate the nature of the impaired mechanisms, extensive testing was done on an individual with especially pure face processing deficits. The results ruled out all extant explanations of prosopagnosia except one that proposed that faces are recognized by a content-specific face processing mechanism. fMRI and MEG studies show that there are a variety of neural profiles in developmental prosopagnosia, which is consistent with behavioral studies demonstrating that it is a heterogeneous disorder.}, Author = {Duchaine, Bradley C. and Nakayama, Ken}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Magnetoencephalography;Visual Pathways;24 Pubmed search results 2008;Magnetic Resonance Imaging;Pattern Recognition, Visual;21 Neurophysiology;Developmental Disabilities;Face;Memory;research support, n.i.h., extramural;Child;Humans;Brain;Prosopagnosia;review;Social Behavior}, Month = {4}, Nlm_Id = {9111376}, Number = {2}, Organization = {Institute of Cognitive Neuroscience, University College London, Alexandra House, 17 Queen Square, London WC1N 3AR, UK. b.duchaine\@ucl.ac.uk}, Pages = {166-73}, Pii = {S0959-4388(06)00028-6}, Pubmed = {16563738}, Title = {Developmental prosopagnosia: a window to content-specific face processing}, Uuid = {0D27C226-6E5D-4436-A9DB-83596EB1B2BD}, Volume = {16}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2006.03.003}} @article{Duchaine:2004, Abstract = {A central question in cognitive neuroscience is whether mechanisms exist that are specialized for particular domains. One of the most commonly cited examples of a domain-specific competence is the human ability to recognize upright faces. However, according to a widely discussed alternative hypothesis, face recognition is instead performed by mechanisms specialized for processing any object class for which an individual has expertise. Faces, according to this domain-general hypothesis, are just one example of an expert class. Nonface object expertise has been intensively investigated using a training procedure involving an artificial stimulus class known as greebles. A key prediction of this hypothesis is that individuals with face recognition impairments will also have impairments with other categories that control subjects have expertise with. Our results show that a man with severe prosopagnosia performed normally throughout the standard greeble training procedure. These findings indicate that face recognition and greeble recognition rely on separate mechanisms.}, Author = {Duchaine, Bradley C. and Dingle, Kerry and Butterworth, Edward and Nakayama, Ken}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Grants; ideas;Photic Stimulation;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Female;Form Perception;Middle Aged;Learning;Reaction Time;Humans;comparative study ;Male;Prosopagnosia;case reports;neurological disorder;21 Circuit structure-function}, Month = {8}, Nlm_Id = {8809320}, Number = {4}, Organization = {Vision Sciences Laboratory, Department of Psychology, Harvard University, 33 Kirkland Street, Cambridge, Massachusetts 02138, USA. brad\@wjh.harvard.edu}, Pages = {469-73}, Pii = {S0896627304004921}, Pubmed = {15312646}, Title = {Normal greeble learning in a severe case of developmental prosopagnosia}, Uuid = {A8C703FC-9CD0-4D55-9333-61350AE7012B}, Volume = {43}, Year = {2004}, url = {papers/Duchaine_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.08.006}} @article{Ducret:2007, Abstract = {The maturation and operation of neural networks are known to depend on modulatory neurons. However, whether similar mechanisms may control both adult and developmental plasticity remains poorly investigated. To examine this issue, we have used the lobster stomatogastric nervous system (STNS) to investigate the ontogeny and role of GABAergic modulatory neurons projecting to small pattern generating networks. Using immunocytochemistry, we found that modulatory input neurons to the stomatogastric ganglion (STG) express GABA only after metamorphosis, a time that coincides with the developmental switch from a single to multiple pattern generating networks within the STNS. We demonstrate that blocking GABA synthesis with 3-mercapto-propionic acid within the adult modulatory neurons results in the reconfiguration of the distinct STG networks into a single network that generates a unified embryonic-like motor pattern. Using dye-coupling experiments, we also found that gap-junctional coupling is greater in embryos and GABA-deprived adults exhibiting the unified motor pattern compared with control adults. Furthermore, GABA was found to diminish directly the extent and strength of electrical coupling within adult STG networks. Together, these observations suggest the acquisition of a GABAergic phenotype by modulatory neurons after metamorphosis may induce the reconfiguration of the single embryonic network into multiple adult networks by directly decreasing electrical coupling. The findings also suggest that adult neural networks retain the ability to express typical embryonic characteristics, indicating that network ontogeny can be reversed and that changes in electrical coupling during development may allow the segregation of multiple distinct functional networks from a single large embryonic network.}, Author = {Ducret, Eric and Le Feuvre, Yves and Meyrand, Pierre and F{\'e}nelon, Val{\'e}rie S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Laboratoire de Neurobiologie des R{\'e}seaux, Universit{\'e} Bordeaux I and Centre National de la Recherche Scientifique, Unit{\'e} Mixte de Recherche 5816, 33405 Talence, France.}, Pages = {3626-38}, Pii = {27/14/3626}, Pubmed = {17409227}, Title = {Removal of GABA within adult modulatory systems alters electrical coupling and allows expression of an embryonic-like network}, Uuid = {88C9B0F4-AF02-4D6C-AFA1-E9C843E17952}, Volume = {27}, Year = {2007}, url = {papers/Ducret_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4406-06.2007}} @article{Duelli:2007, Abstract = {Chromosomal instability (CIN) underlies malignant properties of many solid cancers and their ability to escape therapy, and it might itself cause cancer [1, 2]. CIN is sustained by deficiencies in proteins, such as the tumor suppressor p53 [3-5], that police genome integrity, but the primary cause of CIN in sporadic cancers remains uncertain [6, 7]. The primary suspects are mutations that deregulate telomere maintenance, or mitosis, yet such mutations have not been identified in the majority of sporadic cancers [6]. Alternatively, CIN could be caused by a transient event that destabilizes the genome without permanently affecting mechanisms of mitosis or proliferation [5, 8]. Here, we show that an otherwise harmless virus rapidly causes massive chromosomal instability by fusing cells whose cell cycle is deregulated by oncogenes. This synergy between fusion and oncogenes "randomizes" normal diploid human fibroblasts so extensively that each analyzed cell has a unique karyotype, and some produce aggressive, highly aneuploid, heterogeneous, and transplantable epithelial cancers in mice. Because many viruses are fusogenic, this study suggests that viruses, including those that have not been linked to carcinogenesis, can cause chromosomal instability and, consequently, cancer by fusing cells.}, Author = {Duelli, Dominik M. and Padilla-Nash, Hesed M. and Berman, David and Murphy, Kathleen M. and Ried, Thomas and Lazebnik, Yuri}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Mason-Pfizer monkey virus;Transduction, Genetic;Animals;Humans;Carcinoma;Fibroblasts;Female;research support, n.i.h., intramural;Cell Fusion;Neoplasms;15 Retrovirus mechanism;08 Aberrant cell cycle;Mice, Nude;Oncogenes;Cell Transformation, Viral;research support, n.i.h., extramural;Mice;22 Stem cells;24 Pubmed search results 2008;Chromosomal Instability;Cell Transformation, Neoplastic;22 Cancer}, Month = {3}, Nlm_Id = {9107782}, Number = {5}, Organization = {Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY 11724, USA.}, Pages = {431-7}, Pii = {S0960-9822(07)00888-3}, Pubmed = {17320392}, Title = {A virus causes cancer by inducing massive chromosomal instability through cell fusion}, Uuid = {11C9B88B-91FF-48D3-AE3C-F5D8B386BD91}, Volume = {17}, Year = {2007}, url = {papers/Duelli_CurrBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2007.01.049}} @article{Duemani-Reddy:2008, Abstract = {The dynamic ability of neuronal dendrites to shape and integrate synaptic responses is the hallmark of information processing in the brain. Effectively studying this phenomenon requires concurrent measurements at multiple sites on live neurons. Substantial progress has been made by optical imaging systems that combine confocal and multiphoton microscopy with inertia-free laser scanning. However, all of the systems developed so far restrict fast imaging to two dimensions. This severely limits the extent to which neurons can be studied, as they represent complex three-dimensional structures. Here we present a new imaging system that utilizes a unique arrangement of acousto-optic deflectors to steer a focused, ultra-fast laser beam to arbitrary locations in three-dimensional space without moving the objective lens. As we demonstrate, this highly versatile random-access multiphoton microscope supports functional imaging of complex three-dimensional cellular structures such as neuronal dendrites or neural populations at acquisition rates on the order of tens of kilohertz.}, Author = {Duemani Reddy, Gaddum and Kelleher, Keith and Fink, Rudy and Saggau, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:35:08 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Electric Stimulation;Imaging, Three-Dimensional;Microscopy, Confocal;Dendrites;Rats, Sprague-Dawley;Hippocampus;Rats;technical report;in vitro;research support, u.s. gov't, non-p.h.s.;Microscopy, Fluorescence, Multiphoton;research support, n.i.h., extramural;Animals;Patch-Clamp Techniques;Membrane Potentials;Neurons;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {Department of Bioengineering, Rice University, 6100 Main Street, Suite 116 Keck Hall, Houston, Texas 77005, USA.}, Pages = {713-20}, Pii = {nn.2116}, Pubmed = {18432198}, Title = {Three-dimensional random access multiphoton microscopy for functional imaging of neuronal activity}, Uuid = {BE63200D-7857-4718-8F5A-703BE2502368}, Volume = {11}, Year = {2008}, url = {papers/DuemaniReddy_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2116}} @article{Dufour:2003, Abstract = {The mechanisms generating precise connections between specific thalamic nuclei and cortical areas remain poorly understood. Using axon tracing analysis of ephrin/Eph mutant mice, we provide in vivo evidence that Eph receptors in the thalamus and ephrins in the cortex control intra-areal topographic mapping of thalamocortical (TC) axons. In addition, we show that the same ephrin/Eph genes unexpectedly control the inter-areal specificity of TC projections through the early topographic sorting of TC axons in an intermediate target, the ventral telencephalon. Our results constitute the first identification of guidance cues involved in inter-areal specificity of TC projections and demonstrate that the same set of mapping labels is used differentially for the generation of topographic specificity of TC projections between and within individual cortical areas.}, Author = {Dufour, Audrey and Seibt, Julie and Passante, Lara and Depaepe, Vanessa and Ciossek, Thomas and Fris{\'e}n, Jonas and Kullander, Klas and Flanagan, John G. and Polleux, Franck and Vanderhaeghen, Pierre}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Ephrin-A4;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Ligands;Ephrin-A5;Female;Neural Pathways;Mice, Inbred C57BL;Receptor, EphA5;Mice, Transgenic;Brain Mapping;comment;Animals;Mice;Cerebral Cortex;Receptor, EphA4;Thalamus}, Medline = {22778824}, Month = {7}, Nlm_Id = {8809320}, Number = {3}, Organization = {IRIBHM, University of Brussels (U.L.B.), 808 Route de Lennik, B-1070 Brussels, Belgium.}, Pages = {453-65}, Pii = {S0896627303004409}, Pubmed = {12895420}, Title = {Area specificity and topography of thalamocortical projections are controlled by ephrin/Eph genes}, Uuid = {7D26F2ED-7E38-4693-B045-8ED77E966F42}, Volume = {39}, Year = {2003}, url = {papers/Dufour_Neuron2003.pdf}} @article{Dugas:2006, Abstract = {To better understand the molecular mechanisms governing oligodendrocyte (OL) differentiation, we have used gene profiling to quantitatively analyze gene expression in synchronously differentiating OLs generated from pure oligodendrocyte precursor cells in vitro. By comparing gene expression in these OLs to OLs generated in vivo, we discovered that the program of OL differentiation can progress normally in the absence of heterologous cell-cell interactions. In addition, we found that OL differentiation was unexpectedly prolonged and occurred in at least two sequential stages, each characterized by changes in distinct complements of transcription factors and myelin proteins. By disrupting the normal dynamic expression patterns of transcription factors regulated during OL differentiation, we demonstrated that these sequential stages of gene expression can be independently controlled. We also uncovered several genes previously uncharacterized in OLs that encode transmembrane, secreted, and cytoskeletal proteins that are as highly upregulated as myelin genes during OL differentiation. Last, by comparing genomic loci associated with inherited increased risk of multiple sclerosis (MS) to genes regulated during OL differentiation, we identified several new positional candidate genes that may contribute to MS susceptibility. These findings reveal a previously unexpected complexity to OL differentiation and suggest that an intrinsic program governs successive phases of OL differentiation as these cells extend and align their processes, ensheathe, and ultimately myelinate axons.}, Author = {Dugas, Jason C. and Tai, Yu Chuan and Speed, Terence P. and Ngai, John and Barres, Ben A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;research support, non-u.s. gov't;Rats, Sprague-Dawley;Rats;Oligonucleotide Array Sequence Analysis;Gene Expression Regulation;Quantitative Trait Loci;comparative study;research support, n.i.h., extramural;Protein Array Analysis;Animals;Cells, Cultured;Oligodendroglia;24 Pubmed search results 2008;Transcription Factors}, Month = {10}, Nlm_Id = {8102140}, Number = {43}, Organization = {Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305, USA. jcdugas\@alum.mit.edu}, Pages = {10967-83}, Pii = {26/43/10967}, Pubmed = {17065439}, Title = {Functional genomic analysis of oligodendrocyte differentiation}, Uuid = {31F1BEC8-9DCC-4A59-B5ED-4071C5EAA46A}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2572-06.2006}} @article{Duke:2004, Abstract = {The cell culture model utilized in this study represents one of the most widely used paradigms of microglia in vitro. After 14 days, microglia harvested from the neonatal rat brain are considered 'mature'. However, it is clear that this represents a somewhat arbitrary definition. In this paper, we provide a transcriptome definition of such microglial cells. More than 7,000 known genes and 1,000 expressed sequence tag clusters were analysed. 'Microglia genes' were defined as sequences consistently expressed in all microglia samples tested. Accordingly, 388 genes were identified as microglia genes. Another 1,440 sequences were detected in a subset of the cultures. Genes consistently expressed by microglia included genes known to be involved in the cellular immune response, brain tissue surveillance, microglial migration as well as proliferation. The expression profile reported here provides a baseline against which changes of microglia in vitro can be examined. Importantly, expression profiling of normal microglia will help to provide the presently purely operational definition of 'microglial activation' with a molecular biological correlate. Furthermore, the data reported here add to our understanding of microglia biology and allow projections as to what functions microglia may exert in vivo, as well as in vitro.}, Author = {Duke, D. C. and Moran, L. B. and Turkheimer, F. E. and Banati, R. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {11 Glia}, Nlm_Id = {7809375}, Number = {1}, Organization = {Department of Neuropathology, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, London, UK.}, Pages = {30-7}, Pii = {DNE2004026001030}, Pubmed = {15509896}, Title = {Microglia in culture: what genes do they express?}, Uuid = {38D082FA-3AA6-4D7D-B04A-CEEC8B0FE8D2}, Volume = {26}, Year = {2004}, url = {papers/Duke_DevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000080709}} @article{Dulla:2005, Abstract = {In addition to affecting respiration and vascular tone, deviations from normal CO(2) alter pH, consciousness, and seizure propensity. Outside the brainstem, however, the mechanisms by which CO(2) levels modify neuronal function are unknown. In the hippocampal slice preparation, increasing CO(2), and thus decreasing pH, increased the extracellular concentration of the endogenous neuromodulator adenosine and inhibited excitatory synaptic transmission. These effects involve adenosine A(1) and ATP receptors and depend on decreased extracellular pH. In contrast, decreasing CO(2) levels reduced extracellular adenosine concentration and increased neuronal excitability via adenosine A(1) receptors, ATP receptors, and ecto-ATPase. Based on these studies, we propose that CO(2)-induced changes in neuronal function arise from a pH-dependent modulation of adenosine and ATP levels. These findings demonstrate a mechanism for the bidirectional effects of CO(2) on neuronal excitability in the forebrain.}, Author = {Dulla, Chris G. and Dobelis, Peter and Pearson, Tim and Frenguelli, Bruno G. and Staley, Kevin J. and Masino, Susan A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Hydrogen-Ion Concentration;Receptors, Purinergic P2;Acids;Epilepsy;research support, non-u.s. gov't ;24 Pubmed search results 2008;Up-Regulation;Adenosine Triphosphatases;Receptor, Adenosine A1;Animals;Adenosine Triphosphate;Hippocampus;Synaptic Transmission;Extracellular Fluid;research support, n.i.h., extramural;Organ Culture Techniques;research support, n.i.h., extramural ;Membrane Potentials;Adenosine;21 Activity-development;Rats, Sprague-Dawley;Carbon Dioxide;Rats;Patch-Clamp Techniques;Hypercapnia;Hypocapnia;research support, non-u.s. gov't;21 Neurophysiology;Neurons;Excitatory Postsynaptic Potentials}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Neuroscience Program, Department of Neurology, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.}, Pages = {1011-23}, Pii = {S0896-6273(05)00950-5}, Pubmed = {16364904}, Title = {Adenosine and ATP link PCO2 to cortical excitability via pH}, Uuid = {C00F1394-F406-4BD1-9F99-24DDF77D0044}, Volume = {48}, Year = {2005}, url = {papers/Dulla_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.11.009}} @article{Dunlap:2006, Abstract = {Endogenous retroviruses (ERVs) are fixed and abundant in the genomes of vertebrates. Circumstantial evidence suggests that ERVs play a role in mammalian reproduction, particularly placental morphogenesis, because intact ERV envelope genes were found to be expressed in the syncytiotrophoblasts of human and mouse placenta and to elicit fusion of cells in vitro. We report here in vivo and in vitro experiments finding that the envelope of a particular class of ERVs of sheep, endogenous Jaagsiekte sheep retroviruses (enJSRVs), regulates trophectoderm growth and differentiation in the periimplantation conceptus (embryo/fetus and associated extraembryonic membranes). The enJSRV envelope gene is expressed in the trophectoderm of the elongating ovine conceptus after day 12 of pregnancy. Loss-of-function experiments were conducted in utero by injecting morpholino antisense oligonucleotides on day 8 of pregnancy that blocked enJSRV envelope protein production in the conceptus trophectoderm. This approach retarded trophectoderm outgrowth during conceptus elongation and inhibited trophoblast giant binucleate cell differentiation as observed on day 16. Pregnancy loss was observed by day 20 in sheep receiving morpholino antisense oligonucleotides. In vitro inhibition of the enJSRV envelope reduced the proliferation of mononuclear trophectoderm cells isolated from day 15 conceptuses. Consequently, these results demonstrate that the enJSRV envelope regulates trophectoderm growth and differentiation in the periimplantation ovine conceptus. This work supports the hypothesis that ERVs play fundamental roles in placental morphogenesis and mammalian reproduction.}, Author = {Dunlap, Kathrin A. and Palmarini, Massimo and Varela, Mariana and Burghardt, Robert C. and Hayashi, Kanako and Farmer, Jennifer L. and Spencer, Thomas E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Pregnancy;Cell Differentiation;research support, n.i.h., extramural ;Embryo Implantation;Animals;Humans;Female;Sheep;15 Retrovirus mechanism;Trophoblasts;Endogenous Retroviruses;research support, non-u.s. gov't ;Mice;24 Pubmed search results 2008;Jaagsiekte sheep retrovirus;15 ERVs retroelements;Oligonucleotides, Antisense;Viral Proteins}, Month = {9}, Nlm_Id = {7505876}, Number = {39}, Organization = {Center for Animal Biotechnology and Genomics, Department of Animal Science, Texas A&M University, College Station, TX 77843, USA.}, Pages = {14390-5}, Pii = {0603836103}, Pubmed = {16980413}, Title = {Endogenous retroviruses regulate periimplantation placental growth and differentiation}, Uuid = {6B785E0C-2917-47FF-9AD8-146B742B2DA5}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0603836103}} @article{Dunnett:1987, Abstract = {The capacity of dopamine (DA)-rich embryonic grafts to influence performance in a skilled motor task has been assessed. In two separate experiments, unilateral 6-hydroxydopamine lesions of forebrain DA systems induced a neglect of the contralateral limb and an almost total preference for use of the ipsilateral limb when reaching through the bars of a cage for food pellets. If the food paw was restrained, either by a bracelet or by injection of a local anaesthetic, the lesioned rats would continue to make many reaching attempts with the contralateral paw, but on the great majority of these attempts they were unsuccessful in grasping or retrieving food. DA-rich grafts, reinnervating the denervated caudate-putamen, provided no detectable benefit to the lesioned rats, neither in reducing the ipsilateral bias in their side preference, nor in increasing their success when constrained to reaching with the contralateral limb. This failure to benefit from the grafts is not due to the grafts themselves not being viable, since the same rats showed substantial compensation of whole body motor asymmetries in spontaneous and drug-induced rotation, and a reduction of asymmetry in a battery of neurological tests of sensorimotor function. The results are discussed in terms of the degree of anatomical integration of the grafts into the host neural circuitry, and the neural organization necessary for the performance of different classes of behavior. 0006-8993 Journal Article}, Author = {Dunnett, S. B. and Whishaw, I. Q. and Rogers, D. C. and Jones, G. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:52 -0400}, Journal = {Brain Res}, Keywords = {Motor Skills/drug effects/*physiology;Corpus Striatum/drug effects/*physiology;Animals;Rats;Forelimb/physiology;Substantia Nigra/drug effects/physiology;Female;Rats, Inbred Strains;Apomorphine/pharmacology;17 Transplant Regeneration;Dopamine/metabolism/*physiology;Support, Non-U.S. Gov't;Methamphetamine/pharmacology;L abstr;Stereotyped Behavior/drug effects/physiology;Mesencephalon/cytology/embryology/*transplantation;Laterality/physiology;Hydroxydopamines/diagnostic use;Oxidopamine}, Number = {1}, Pages = {63-78}, Pubmed = {3113665}, Title = {Dopamine-rich grafts ameliorate whole body motor asymmetry and sensory neglect but not independent limb use in rats with 6-hydroxydopamine lesions}, Uuid = {7501B4BA-EC80-11DA-8605-000D9346EC2A}, Volume = {415}, Year = {1987}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3113665}} @article{Dupont:2006, Abstract = {The immature cerebral cortex self-organizes into local neuronal clusters long before it is activated by patterned sensory inputs. In the cortical anlage of newborn mammals, neurons coassemble through electrical or chemical synapses either spontaneously or by activation of transmitter-gated receptors. The neuronal network and the cellular mechanisms underlying this cortical self-organization process during early development are not completely understood. Here we show in an intact in vitro preparation of the immature mouse cerebral cortex that neurons are functionally coupled in local clusters by means of propagating network oscillations in the beta frequency range. In the newborn mouse, this activity requires an intact subplate and is strongly synchronized within a cortical column by gap junctions. With the developmental disappearance of the subplate at the end of the first postnatal week, activation of NMDA (N-methyl-D-aspartate) receptors in the immature cortical network is essential to generate this columnar activity pattern. Our findings show that during a brief developmental period the cortical network switches from a subplate-driven, gap-junction-coupled syncytium to a synaptic network acting through NMDA receptors to generate synchronized oscillatory activity, which may function as an early functional template for the development of the cortical columnar architecture.}, Author = {Dupont, Erwan and Hanganu, Ileana L. and Kilb, Werner and Hirsch, Silke and Luhmann, Heiko J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-28 17:16:42 +0000}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Synapses;Gap Junctions;21 Cortical oscillations;24 Pubmed search results 2008;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;Mice, Inbred C57BL;Animals, Newborn;Electrophysiology;Somatosensory Cortex;Animals;Carbachol;Mice;Neurons;Receptors, N-Methyl-D-Aspartate; in vitro}, Month = {1}, Nlm_Id = {0410462}, Number = {7072}, Organization = {Institute of Physiology and Pathophysiology, Johannes Gutenberg University of Mainz, Duesbergweg 6, D-55128 Mainz, Germany.}, Pages = {79-83}, Pii = {nature04264}, Pubmed = {16327778}, Title = {Rapid developmental switch in the mechanisms driving early cortical columnar networks}, Uuid = {6AD30279-AC78-48EA-B100-95C574CFA3F4}, Volume = {439}, Year = {2006}, url = {papers/Dupont_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04264}} @article{Dupressoir:2005, Abstract = {Recently, we and others have identified two human endogenous retroviruses that entered the primate lineage 25-40 million years ago and that encode highly fusogenic retroviral envelope proteins (syncytin-1 and -2), possibly involved in the formation of the placenta syncytiotrophoblast layer generated by trophoblast cell fusion at the materno-fetal interface. A systematic in silico search throughout mouse genome databases presently identifies two fully coding envelope genes, present as unique copies and unrelated to any known murine endogenous retrovirus, that we named syncytin-A and -B. Quantitative RT-PCR demonstrates placenta-specific expression for both genes, with increasing transcript levels in this organ from 9.5 to 14.5 days postcoitum. In situ hybridization of placenta cryosections further localizes these transcripts in the syncytiotrophoblast-containing labyrinthine zona. Consistently, we show that both genes can trigger cell-cell fusion in ex vivo transfection assays, with distinct cell type specificities suggesting different receptor usage. Genes orthologous to syncytin-A and -B and disclosing a striking conservation of their coding status are found in all Muridae tested (mouse, rat, gerbil, vole, and hamster), dating their entry into the rodent lineage approximately 20 million years ago. Together, these data strongly argue for a critical role of syncytin-A and -B in murine syncytiotrophoblast formation, thus unraveling a rather unique situation where two pairs of endogenous retroviruses, independently acquired by the primate and rodent lineages, would have been positively selected for a convergent physiological role.}, Author = {Dupressoir, Anne and Marceau, Geoffroy and Vernochet, C{\'e}cile and B{\'e}nit, Laurence and Kanellopoulos, Colette and Sapin, Vincent and Heidmann, Thierry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Gene Products, env;Placenta;Animals;Base Sequence;Evolution, Molecular;Cell Fusion;Trophoblasts;Endogenous Retroviruses;15 Retrovirus mechanism;RNA, Messenger;Genes, env;Organ Specificity;Pregnancy Proteins;Mice;24 Pubmed search results 2008;Molecular Sequence Data;15 ERVs retroelements;Selection (Genetics);Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {7505876}, Number = {3}, Organization = {Unit{\'e} des R{\'e}trovirus Endog\`{e}nes et El{\'e}ments R{\'e}tro{\"\i}des des Eucaryotes Sup{\'e}rieurs, Unit{\'e} Mixte de Recherche, 8122 Centre National de la Recherche Scientifique, Institut Gustave Roussy, 94805 Villejuif, France.}, Pages = {725-30}, Pii = {0406509102}, Pubmed = {15644441}, Title = {Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae}, Uuid = {9DD5EBF2-EE51-11DA-8605-000D9346EC2A}, Volume = {102}, Year = {2005}, url = {papers/Dupressoir_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0406509102}} @article{Dupret:2007, Abstract = {The role of adult hippocampal neurogenesis in spatial learning remains a matter of debate. Here, we show that spatial learning modifies neurogenesis by inducing a cascade of events that resembles the selective stabilization process characterizing development. Learning promotes survival of relatively mature neurons, apoptosis of more immature cells, and finally, proliferation of neural precursors. These are three interrelated events mediating learning. Thus, blocking apoptosis impairs memory and inhibits learning-induced cell survival and cell proliferation. In conclusion, during learning, similar to the selective stabilization process, neuronal networks are sculpted by a tightly regulated selection and suppression of different populations of newly born neurons.}, Author = {Dupret, David and Fabre, Annabelle and D{\"o}br{\"o}ssy, M\`{a}t\`{e} D\`{a}niel and Panatier, Aude and Rodr{\'\i}guez, Jos{\'e} Julio and Lamarque, St{\'e}phanie and Lemaire, Valerie and Oliet, Stephane H. R. and Piazza, Pier-Vincenzo V. and Abrous, Djoher Nora}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {101183755}, Number = {8}, Organization = {INSERM U862, Bordeaux Neuroscience Research Center, Bordeaux, France.}, Pages = {e214}, Pii = {07-PLBI-RA-0438}, Pubmed = {17683201}, Title = {Spatial learning depends on both the addition and removal of new hippocampal neurons}, Uuid = {897AEE30-1C20-4876-9DCE-D86F09503122}, Volume = {5}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0050214}} @article{Durand:2006, Abstract = {We have established a quantitative reverse transcriptase-PCR (RT-PCR) approach for the analysis of RNA transcript levels in individual cells of living brain slices. Quantification is achieved by using rapid-cycle, real-time PCR protocols and high-resolution external cDNA standard curves for the gene of interest. The method consists of several procedures, including cell soma harvest, reverse transcription, and an optimized cDNA purification step, which allowed us to quantify transcripts in small types of neurons, like cerebellar granule cells. Thus, we detected in single granule cells an average of 20 transcript copies of the housekeeping gene glyceraldehyde-3-phosphate-dehydrogenase. We combined two-photon calcium imaging and quantitative RT-PCR in single Purkinje and granule cells, respectively, and identified distinct glutamate receptor-dependent Ca(2+) responses in these two cell types. The approach was further tested by profiling the expression of the ionotropic glutamate receptor subunits NR2B and NR2C in the cerebellum. Our study revealed a developmental switch from an average of 15 NR2B copies/cell at postnatal day 8 (P8) to about five NR2C copies/cell after P26. Taken together, our results demonstrate that the new method is rapid, highly sensitive, provides reliable results in neurons of various sizes, and can be used in combination with Ca(2+) imaging.}, Author = {Durand, and Marandi, and Herberger, and Blum, and Konnerth,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0031-6768}, Journal = {Pflugers Arch}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {0154720}, Number = {6}, Organization = {Institut f{\"u}r Physiologie, Ludwig-Maximilians-Universit{\"a}t, Pettenkofer Stra$\beta$e 12, 80336, Mnchen, Germany, blum\@lrz.uni-muenchen.de.}, Pages = {716-726}, Pubmed = {16211366}, Title = {Quantitative single-cell RT-PCR and Ca(2+) imaging in brain slices}, Uuid = {0D317B0A-DD4B-4754-A73F-72C7CD76FACC}, Volume = {451}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00424-005-1514-3}} @article{Durbec:2001, Abstract = {In vertebrates, interneurons of the olfactory bulb are continuously generated postnatally and throughout life at the subventricular zone of the forebrain. From there, the neuronal progenitors migrate tangentially in a typical chain-like structure to the olfactory bulb in which they differentiate as interneurons. We have used a mouse/chick xenograft strategy to explore the migration and differentiation potential of the mouse olfactory progenitors in a heterochronic and heterotypic environment. We compared the migration of primary cells derived from the subventricular zone of adult or newborn lateral ventricule with the behavior of in vitro amplified cells derived from the same structures. We show that in the chick environment, olfactory bulb progenitors from newborn brain tissue perform chain migration along the neural crest cell routes, whereas grafted neurosphere-derived- cells migrate as isolated cells. These results, together with in vitro observations, allow us to propose that neuronal chain migration is a community effect independent of environmental cues but which is closely regulated by the differentiation program of the cells. We established that the progenitor cells performing chain migration are already committed, while neurosphere-derived-cells are able to integrate and differentiate as components of the peripheral nervous system. Copyright 2001 Academic Press.}, Author = {Durbec, P. and Rougon, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:45 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {Interneurons/chemistry/*cytology/*transplantation;Neural Cell Adhesion Molecules/analysis;Olfactory Bulb/*cytology;Tubulin/analysis;Transplantation, Heterologous;Vimentin/analysis;Sialic Acids/analysis;Tyrosine 3-Monooxygenase/analysis;L pdf;Animal;Mammals;17 Transplant Regeneration;Stem Cells/chemistry/*cytology/*transplantation;Support, Non-U.S. Gov't;Chick Embryo;Mice, Inbred Strains;Animals, Newborn;Graft Survival/physiology;Age Factors;Cell Movement/physiology;Intermediate Filament Proteins/analysis;Cell Differentiation/physiology;Mice;*Brain Tissue Transplantation}, Number = {3}, Organization = {Laboratoire de Genetique et Physiologie du Developpement, IBDM, CNRS/INSERM/Universite de la Mediterranee/AP de Marseille, Parc Scientifique de Luminy, Marseille Cedex 9, 13288, France.}, Pages = {561-76.}, Title = {Transplantation of mammalian olfactory progenitors into chick hosts reveals migration and differentiation potentials dependent on cell commitment}, Uuid = {E4EFB43A-EE51-437B-A09D-AC7E73D0F14F}, Volume = {17}, Year = {2001}, url = {papers/Durbec_MolCellNeurosci2001.pdf}} @article{Durbec:2001a, Abstract = {Since its first description the polysialylated form of NCAM (PSA-NCAM) is thought to be a major regulator of cell-cell interactions in the nervous system. Over the past few years many crucial questions have been answered concerning PSA biosynthesis and function. Among these are the identification and cloning of the key enzymes that are responsible for its synthesis and the fact that expression of PSA is not restricted to developmental stages but maintained in the adult nervous system. In the adult, PSA has been shown to be not only a marker of structural plasticity but seems to be a major player in these processes. Originally suggested to be a purely anti-adhesive factor, modulating cell-cell interactions in general and by this allowing plasticity, there is now increasing evidence that this might not be the whole story. Instead, it appears possible that PSA-NCAM interacts with secreted signaling molecules and by this fulfills a more instructive function in brain plasticity.}, Author = {Durbec, P. and Cremer, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0893-7648}, Journal = {Mol Neurobiol}, Keywords = {Axons;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Neural Cell Adhesion Molecules;Nervous System Physiology;Cell Communication;Neural Cell Adhesion Molecule L1;Neuronal Plasticity;Humans;Cell Movement;Sialic Acids;review;Animals}, Medline = {21820121}, Nlm_Id = {8900963}, Number = {1-3}, Organization = {Laboratoire de G{\'e}n{\'e}tique et Physiologie du D{\'e}veloppement, Developmental Biology Institute of Marseille, Universit{\'e} de la M{\'e}diterran{\'e}e, France.}, Pages = {53-64}, Pii = {MN:24:1-3:053}, Pubmed = {11831554}, Title = {Revisiting the function of PSA-NCAM in the nervous system}, Uuid = {6938CC3D-DD2B-4AF0-8AED-28A2071DD7E4}, Volume = {24}, Year = {2001}} @article{Dymecki:2007, Abstract = {New genetic technologies are transforming nervous system studies in mice, impacting fields from neural development to the neurobiology of disease. Alongside these methodological advances, new concepts are taking shape with respect to both vocabulary and form. Here we review aspects of both burgeoning areas. Presented are technologies which, by co-opting site-specific recombinase systems, enable select genes to be turned on or off in specific brain cells of otherwise undisturbed mouse embryos or adults. Manipulated genes can be endogenous loci or inserted transgenes encoding reporter, sensor, or effector molecules, making it now possible to assess not only gene function, but also cell function, origin, fate, connectivity, and behavioral output. From these methodological advances, a new form of molecular neuroscience is emerging that may be said to lean on the concepts of genetic access, genetic lineage, and genetic anatomy-the three "Gs"-much like a general education rests on the basics of reading, 'riting, and 'rithmetic.}, Author = {Dymecki, Susan M. and Kim, Jun Chul}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;24 Pubmed search results 2008;23 Technique}, Month = {4}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.}, Pages = {17-34}, Pii = {S0896-6273(07)00205-X}, Pubmed = {17408575}, Title = {Molecular Neuroanatomy's "Three Gs": A Primer}, Uuid = {747622AE-BA34-4963-B9B2-9D41414A30DF}, Volume = {54}, Year = {2007}, url = {papers/Dymecki_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.03.009}} @article{Dzhala:2003, Abstract = {In the developing rat hippocampus, ictal epileptiform activity can be elicited easily in vitro during the first three postnatal weeks. Changes in neuronal ion transport during this time cause the effects of GABA(A) receptor (GABA(A)-R) activation to shift gradually from strongly depolarizing to hyperpolarizing. It is not known whether the depolarizing effects of GABA and the propensity for ictal activity are causally linked. A key question is whether the GABA-mediated depolarization is excitatory, which we defined operationally as being sufficient to trigger action potentials. We assessed the effect of endogenous GABA on ictal activity and neuronal firing rate in hippocampal slices from postnatal day 1 (P1) to P30. In extracellular recordings, there was a strong correlation between the postnatal age at which GABA(A)-R antagonists decreased action potential frequency (P23) and the age at which ictal activity could be induced by elevated potassium (P23). In addition, there was a strong correlation between the fraction of slices in which ictal activity was induced by elevated potassium concentrations and the fractional decrease in action potential firing when GABA(A)-Rs were blocked in the presence of ionotropic glutamate receptor antagonists. Finally, ictal activity induced by elevated potassium was blocked by the GABA(A)-R antagonists bicuculline and SR-95531 (gabazine) and increased in frequency and duration by GABA(A)-R agonists isoguvacine and muscimol. Thus, the propensity of the developing hippocampus for ictal activity is highly correlated with the effect of GABA on action potential probability and reversed by GABA(A) antagonists, indicating that GABA-mediated excitation is causally linked to ictal activity in this developmental window.}, Author = {Dzhala, Volodymyr I. and Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {GABA Agonists;Excitatory Amino Acid Antagonists;gamma-Aminobutyric Acid;Animals;Aging;Rats;research support, u.s. gov't, p.h.s. ;Patch-Clamp Techniques;Epilepsy;in vitro ;Hippocampus;Rats, Wistar;Male;Potassium;Action Potentials;Animals, Newborn;Receptors, GABA-A;21 Neurophysiology;Neurons;research support, u.s. gov't, p.h.s.;GABA Antagonists;24 Pubmed search results 2008;in vitro}, Month = {3}, Nlm_Id = {8102140}, Number = {5}, Organization = {Department of Neurology and Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.}, Pages = {1840-6}, Pii = {23/5/1840}, Pubmed = {12629188}, Title = {Excitatory actions of endogenously released GABA contribute to initiation of ictal epileptiform activity in the developing hippocampus}, Uuid = {B9679963-353E-4B94-9477-5FA8B105D336}, Volume = {23}, Year = {2003}, url = {papers/Dzhala_JNeurosci2003.pdf}} @article{Dzhala:2003a, Abstract = {The transition from brief bursts of synchronous population activity characteristic of interictal epileptiform discharges (IEDs) to more prolonged epochs of population activity characteristic of seizures (ictal-like activity) was recorded in juvenile rat hippocampal-entorhinal cortex slices and hippocampal slices using multiple-site extracellular electrodes. Epileptiform activity was elicited by either increased extracellular potassium or 4-AP. IEDs originated in the CA3 a-b region and spread bidirectionally into CA1 and CA3c dentate gyrus. The transition from IEDs to ictal-like sustained epileptiform activity was reliably preceded by (1) increase in IED propagation velocity, (2) increase in IED secondary afterdischarges and their reverberation between CA3a and CA3c, and (3) shift in the IED initiation area from CA3 a-b to CA3c. Ictal-like sustained network oscillations (10-20 Hz) originated in CA3c and spread to CA1. The pattern of hippocampal ictal-like activity was unaffected by removal of the entorhinal cortex. These findings indicate that interictal and ictal activity can originate in the same neural network, and that the transition from interictal to ictal-like-sustained activity is preceded by predictable alterations in the origin and spread of IEDs. These findings elucidate new targets for investigating the proximate causes, prediction, and treatment of seizures.}, Author = {Dzhala, Volodymyr I. and Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, u.s. gov't, p.h.s.;21 Epilepsy;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Rats;Action Potentials;Dentate Gyrus;Pyramidal Cells;Rats, Wistar;Seizures;Hippocampus;Nerve Net;Animals;Cells, Cultured;24 Pubmed search results 2008;Entorhinal Cortex;Male}, Month = {8}, Nlm_Id = {8102140}, Number = {21}, Organization = {Department of Neurology and Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.}, Pages = {7873-80}, Pii = {23/21/7873}, Pubmed = {12944517}, Title = {Transition from interictal to ictal activity in limbic networks in vitro}, Uuid = {43CD73B8-9105-40A9-BD99-7D9A962677AE}, Volume = {23}, Year = {2003}, url = {papers/Dzhala_JNeurosci2003a.pdf}} @article{Dzhala:2004, Abstract = {Hippocampal fast ripples (FRs) have been associated with seizure onset in both human and experimental epilepsy. To characterize the mechanisms underlying FR oscillations (200-600 Hz), we studied activity of single neurons and neuronal networks in rat hippocampal slices in vitro. The correlation between the action potentials of bursting pyramidal cells and local field potential oscillations suggests that synchronous onset of action potential bursts and similar intrinsic firing patterns among local neurons are both necessary conditions for FR oscillations. Increasing the fidelity of individual pyramidal cell spike train timing by blocking accommodation dramatically increased FR amplitude, whereas blockade of potassium conductances decreased the fidelity of action potential timing in individual pyramidal cell action potential bursts and decreased FR amplitude. Blockade of ionotropic glutamate receptors desynchronized onset of action potential bursts in individual pyramidal cells and abolished fast ripples. Thus, synchronous burst onset mediated by recurrent excitatory synaptic transmission and similar intrinsic spike timing mechanisms in neighboring pyramidal cells are necessary conditions for FR oscillations within the hippocampal network.}, Author = {Dzhala, Volodymyr I. and Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Animals;Cells, Cultured;Rats;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;21 Epilepsy;2-Amino-5-phosphonovalerate;Periodicity;Kinetics;Hippocampus;Pyramidal Cells;Receptors, AMPA;Rats, Wistar;Male;Quinoxalines;Action Potentials;21 Neurophysiology;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate}, Month = {10}, Nlm_Id = {8102140}, Number = {40}, Organization = {Department of Neurology and Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.}, Pages = {8896-906}, Pii = {24/40/8896}, Pubmed = {15470156}, Title = {Mechanisms of fast ripples in the hippocampus}, Uuid = {B944E9FC-8B8C-4F21-B8B7-AC047494CE25}, Volume = {24}, Year = {2004}, url = {papers/Dzhala_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3112-04.2004}} @article{Dzhala:2005, Abstract = {During development, activation of Cl(-)-permeable GABA(A) receptors (GABA(A)-R) excites neurons as a result of elevated intracellular Cl(-) levels and a depolarized Cl(-) equilibrium potential (E(Cl)). GABA becomes inhibitory as net outward neuronal transport of Cl(-) develops in a caudal-rostral progression. In line with this caudal-rostral developmental pattern, GABAergic anticonvulsant compounds inhibit motor manifestations of neonatal seizures but not cortical seizure activity. The Na(+)-K(+)-2Cl(-) cotransporter (NKCC1) facilitates the accumulation of Cl(-) in neurons. The NKCC1 blocker bumetanide shifted E(Cl) negative in immature neurons, suppressed epileptiform activity in hippocampal slices in vitro and attenuated electrographic seizures in neonatal rats in vivo. Bumetanide had no effect in the presence of the GABA(A)-R antagonist bicuculline, nor in brain slices from NKCC1-knockout mice. NKCC1 expression level versus expression of the Cl(-)-extruding transporter (KCC2) in human and rat cortex showed that Cl(-) transport in perinatal human cortex is as immature as in the rat. Our results provide evidence that NKCC1 facilitates seizures in the developing brain and indicate that bumetanide should be useful in the treatment of neonatal seizures.}, Author = {Dzhala, Volodymyr I. and Talos, Delia M. and Sdrulla, Dan A. and Brumback, Audrey C. and Mathews, Gregory C. and Benke, Timothy A. and Delpire, Eric and Jensen, Frances E. and Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {research support, n.i.h., extramural ;Rats, Long-Evans;Animals;Bumetanide;Gene Expression Regulation, Developmental;Rats;Seizures;Phenobarbital;comparative study;Humans;Sodium-Potassium-Chloride Symporters;21 Epilepsy;Infant;Hippocampus;Kainic Acid;comparative study ;research support, non-u.s. gov't;research support, non-u.s. gov't ;Animals, Newborn;Cerebral Cortex;21 Neurophysiology;Diuretics;Membrane Potentials;research support, n.i.h., extramural;24 Pubmed search results 2008;Immunohistochemistry;Electroencephalography;Anticonvulsants}, Month = {11}, Nlm_Id = {9502015}, Number = {11}, Organization = {Department of Neurology, School of Medicine, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado 80262, USA.}, Pages = {1205-13}, Pii = {nm1301}, Pubmed = {16227993}, Title = {NKCC1 transporter facilitates seizures in the developing brain}, Uuid = {6062B065-82F2-457E-A2F4-100054FEF7E2}, Volume = {11}, Year = {2005}, url = {papers/Dzhala_NatMed2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm1301}} @article{Dziembowska:2005, Abstract = {Oligodendrocyte development is controlled by a number of survival and migratory factors. The present study shows that signaling of CXCR4 receptor by the chemokine CXCL12 regulates survival and migration of neural precursors (NP) as well as oligodendrocyte progenitors (OP). CXCR4 is expressed by E14 striatal NP and OP generated by neurospheres. In CXCR4-defective mice, the number of NP in neurosphere outgrowth was twofold less than in wild-type (WT) mice; NP radial cell migration was also decreased. In contrast, the addition of CXCL12 to WT NP increased radial migration from the sphere in a dose-dependent manner with a maximal response at 200 nM. When oligodendrocytes differentiated in neurosphere outgrowth, CXCR4 was downregulated. OP isolated from newborn brain coexpressed CXCR4 with platelet-derived growth factor receptor-alpha (PDGFR alpha) or chondroitin sulfate proteoglycan; receptor expression also decreased during differentiation in vitro. Neonatal OP showed a peak migratory response to 20 nM of CXCL12 in chemotactic chambers, a migration inhibited by a CXCR4 antagonist and anti-CXCL12 antibody. In the embryonic spinal cord, the number of OP-expressing PDGFR alpha was reduced more than twofold in CXCR4-defective mice compared with WT and the ratio of ventral to dorsal OP was significantly increased. This indicates a defect in OP survival and their dorsal migration from the ventral cord region, probably because CXCR4(-/-) OP are unable to respond to CXCL12 made by vascular endothelia and the pia mater. We propose that CXCR4 signaling regulate survival and outward chemotactic migration of OP during embryonic and postnatal CNS development.}, Author = {Dziembowska, M. and Tham, T. N. and Lau, P. and Vitry, S. and Lazarini, F. and Dubois-Dalcq, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Cell Survival;Dose-Response Relationship, Drug;Cell Differentiation;Signal Transduction;Animals;Cells, Cultured;Receptors, CXCR4;Spheroids, Cellular;Oligodendroglia;Cell Count;Cell Movement;Mice, Inbred C57BL;Mice, Knockout;Neurons;Chemokines, CXC;Down-Regulation;Mice;Receptor, Platelet-Derived Growth Factor alpha;24 Pubmed search results 2008;Central Nervous System;Stem Cells;Proteochondroitin Sulfates;Research Support, Non-U.S. Gov't}, Month = {5}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Neuroscience, Pasteur Institute, Paris, France.}, Pages = {258-69}, Pubmed = {15756692}, Title = {A role for CXCR4 signaling in survival and migration of neural and oligodendrocyte precursors}, Uuid = {72C1ED51-39C7-4BC6-8824-88F22C9D6145}, Volume = {50}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20170}} @article{Eagleson:2007, Abstract = {The cre/loxP system is used routinely to manipulate gene expression in the mouse nervous system. In order to delete genes specifically from the telencephalon, the Foxg1-cre line was created previously by replacing the intron-less Foxg1 coding region with cre, resulting in a Foxg1 heterozygous mouse. As the telencephalon of heterozygous Foxg1 mice was reported to be normal, this genotype often has been used as the control in subsequent analyses. Here we describe substantial disruption of forebrain development of heterozygous mice in the Foxg1-cre line, maintained on the C57BL/6J background. High resolution magnetic resonance microscopy reveals a significant reduction in the volume of the neocortex, hippocampus and striatum. The alteration in the neocortex results, in part, from a decrease in its tangential dimension, although gross patterning of the cortical sheet appears normal. This decrease is observed in three different Foxg1 heterozygous mouse lines, independent of the method of achieving deletion of the Foxg1 gene. Although Foxg1 is not expressed in the diencephalon, three-dimensional magnetic resonance microscopy revealed that thalamic volume in the adult is reduced. In contrast, at postnatal day 4, thalamic volume is normal, suggesting that interactions between cortex and dorsal thalamus postnatally produce the final adult thalamic phenotype. In the Foxg1-cre line maintained on the C57BL/6J background, the radial domain of the cerebral cortex also is disrupted substantially, particularly in supragranular layers. However, neither Foxg1 heterozygous mice of the Foxg1-tet (tetracycline transactivator) line, nor those of the Foxg1-lacZ and Foxg1-cre lines maintained on a mixed background, displayed a reduced cortical thickness. Thus Cre recombinase contributes to the radial phenotype, although only in the context of the congenic C57BL/6J background. These observations highlight an important role for Foxg1 in cortical development, reveal noteworthy complexity in the invocation of specific mechanisms underlying phenotypes expressed following genetic manipulations and stress the importance of including appropriate controls of all genotypes.}, Author = {Eagleson, K. L. and Schlueter McFadyen-Ketchum, L. J. and Ahrens, E. T. and Mills, P. H. and Does, M. D. and Nickols, J. and Levitt, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7605074}, Number = {2}, Organization = {Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University School of Medicine, 8110B Medical Research Building III, 465 21st Avenue South, Nashville, TN 37232, USA. kathie.eagleson\@vanderbilt.edu}, Pages = {385-99}, Pii = {S0306-4522(07)00740-3}, Pubmed = {17640820}, Title = {Disruption of Foxg1 expression by knock-in of cre recombinase: effects on the development of the mouse telencephalon}, Uuid = {4C65A9D2-3581-4242-A2DF-9EC322DA62D5}, Volume = {148}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2007.06.012}} @article{Easter:1985, Abstract = {The generation of specific patterns of neuronal connections has usually been regarded as a central problem in neurobiology. The prevailing view for many years has been that these connections are established by complementary recognition molecules on the pre- and postsynaptic cells (the chemoaffinity theory). Experimental results obtained in the past decade, however, indicate that the view that axon guidance and synaptogenesis proceed according to restrictive chemical markers is too narrow. Although a more rigid plan may prevail in some invertebrates, the formation of specific connections in vertebrates also involves competition between axon terminals, trophic feedback between pre- and postsynaptic cells, and modification of connections by functional activity. 0036-8075 Journal Article}, Author = {Easter, S. S. and Purves, D. and Rakic, P. and Spitzer, N. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2012-11-13 20:49:20 +0000}, Journal = {Science}, Keywords = {Invertebrates/anatomy &histology;*Models, Neurological;Ganglia, Autonomic/anatomy &histology/growth &development;Cell Communication;Nervous System/*anatomy &histology;Synapses/anatomy &histology/physiology;N;Neurons/*anatomy &histology;Support, Non-U.S. Gov't;Animals;Vertebrates/anatomy &histology;Axons/anatomy &histology/physiology;19 Neocortical evolution; Activity-development; Structure-Activity Relationship;development; review literature}, Number = {4725}, Pages = {507-11}, Pubmed = {4048944}, Title = {The changing view of neural specificity}, Uuid = {E3E3CDE2-02B6-4823-9EBC-A7AB53461B6F}, Volume = {230}, Year = {1985}, url = {papers/Easter_Science1985.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4048944}} @article{Eberwine:2001, Author = {Eberwine, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:45 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Human;Alternative Splicing;Gene Expression Regulation;Cells;Molecular Biology;review, tutorial;RNA, Messenger;Animals;Polymerase Chain Reaction;review;23 Technique}, Medline = {21547535}, Month = {11}, Nlm_Id = {9809671}, Organization = {Department of Pharmacology, University of Pennsylvania Medical Center, 36th Street and Hamilton Walk, Philadelphia, Pennsylvania 19104, USA. eberwine\@pharm.med.upenn.edu}, Pages = {1155-6}, Pii = {nn1101-1155}, Pubmed = {11687821}, Title = {Single-cell molecular biology}, Uuid = {F673BD71-8639-4626-84C6-4F7D4E0B9601}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Eberwine_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1101-1155}} @article{Eckenhoff:1984, Abstract = {The cytoarchitectonic organization of the dentate gyrus was analyzed in the rhesus monkey at various embryonic (E) and postnatal (P) ages with the rapid Golgi method, transmission electron microscopy (EM), and immunocytochemical localization of glial fibrillary acidic protein (GFAP). From the earliest ages (stage I, E38-E83), immature granule cells were arranged radially along elongated fibers that extend from the ventricular zone to the pial surface. The glial nature of these radial fibers was confirmed by the presence of GFAP antigen in their cytoplasm detected clearly by E70. EM analysis at this age showed that granule cells situated within the dentate plate, as well as many neurons still migrating from the ventricular zone, were closely apposed to fascicles of radial glial fibers. The radial organization of the dentate plate was even more evident during stage II (E83-E165). Thus, in E97 and E125 specimens, radially oriented immunoreactive glial processes emerged from somas situated either in the ventricular or subgranular zones, penetrated between columns of neurons in the granular layer, branched upon entering the molecular layer, and finally terminated at the pial surface. Palisades of glial processes delineated ontogenetic radial units which consisted of stacks of granule cell bodies in different stages of maturation. In a given radial unit, more mature cells were located superficially (closer to the pial surface) and less mature cells were located at progressively deeper levels. This radial organization of the dentate gyrus was maintained during stage III (P0-P60) and stage IV (2 months-adult). Furthermore, the number of GFAP-positive proliferating cells in the subgranular zone increased from 1 to 5 months. In the mature brain, the radial organization of the dentate gyrus was less apparent although many glial fibers still penetrated the granule cell layer. The present results indicate that the developing dentate gyrus in primates consists of a series of ontogenetic radial units that resemble those described in the fetal neocortex (Rakic, '72). They further suggest that the development and maintenance of this radial columnar organization may be imposed by the orientation of glial scaffolding during development.}, Author = {Eckenhoff, M. F. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Aging;Neuroglia;Golgi Apparatus;Macaca mulatta;Hippocampus;Female;Astrocytes;Research Support, U.S. Gov't, P.H.S.;Cell Division;Microscopy, Electron;Pregnancy;Animals;Macaca;Neurons}, Medline = {84162788}, Month = {2}, Nlm_Id = {0406041}, Number = {1}, Pages = {1-21}, Pubmed = {6707248}, Title = {Radial organization of the hippocampal dentate gyrus: a Golgi, ultrastructural, and immunocytochemical analysis in the developing rhesus monkey}, Uuid = {5E8631FE-698C-11DA-A4B6-000D9346EC2A}, Volume = {223}, Year = {1984}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902230102}} @article{Eckenhoff:1988, Abstract = {The nature of proliferative cells in the subgranular zone (SGZ) of the hippocampal region and the fate of their progeny was analyzed by 3H-thymidine (3H-TdR) autoradiography combined with immunocytochemistry at the light and electron microscopic levels in 18 rhesus monkeys ranging in age from late gestation to 17 years. Our analysis indicates that, during the last quarter of gestation and the first 3 postnatal months, the SGZ produces both glial and neuronal cells. These 2 major classes of cells originate from the 2 precursor lines and, following their mitotic division, migrate to the granular layer. During the juvenile period (4-6 months of age), neuronal production tapers off and most postmitotic cells remaining within the SGZ differentiate into glial elements. In postpubertal animals (3 years and older), the 3H-TdR-labeled cells in the dentate gyrus belong to several non-neuronal classes. The largest group was immunoreactive to the glial fibrillary acidic protein (GFAP) at both the light and electron microscopic levels, indicating their astrocytic nature. The remaining 3H-TdR-labeled, GFAP-negative cells had ultra-structural characteristics of either microglia, oligodendroglia, or their progenitory stem cells. Therefore, there is a continuing addition and/or turnover of the glial cells in the dentate gyrus of sexually mature monkeys, but, in contrast to the massive neurogenesis reported in adult rodents, the production of new neurons could not be detected after puberty. The significance of a stable population of neurons in the hippocampal formation of mature primates is discussed in relation to its possible function in memory.}, Author = {Eckenhoff, M. F. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Thymidine;Aging;Glial Fibrillary Acidic Protein;Macaca mulatta;Immunohistochemistry;Hippocampus;Microscopy, Electron;Autoradiography;Cell Division;Research Support, U.S. Gov't, P.H.S.;Animals;Macaca}, Medline = {88316375}, Month = {8}, Nlm_Id = {8102140}, Number = {8}, Organization = {Section of Neuroanatomy, Yale University School of Medicine, New Haven, Connecticut 06510.}, Pages = {2729-47}, Pubmed = {3411351}, Title = {Nature and fate of proliferative cells in the hippocampal dentate gyrus during the life span of the rhesus monkey}, Uuid = {AD8AEC66-A3E5-11DA-AB00-000D9346EC2A}, Volume = {8}, Year = {1988}} @article{Edenfeld:2005, Abstract = {In all complex organisms, glial cells are pivotal for neuronal development and function. Insects are characterized by having only a small number of these cells, which nevertheless display a remarkable molecular diversity. An intricate relationship between neurons and glia is initially required for glial migration and during axonal patterning. Recent data suggest that in organisms such as Drosophila, a prime role of glial cells lies in setting boundaries to guide and constrain axonal growth.}, Author = {Edenfeld, Gundula and Stork, Tobias and Kl{\"a}mbt, Christian}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Institut f{\"u}r Neurobiologie, Universit{\"a}t M{\"u}nster, Badestr. 9, 48149 M{\"u}nster, Germany.}, Pages = {34-9}, Pii = {S0959-4388(05)00008-5}, Pubmed = {15721742}, Title = {Neuron-glia interaction in the insect nervous system}, Uuid = {34DAFB0E-F2C9-43AA-8AF5-80F58751FF86}, Volume = {15}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.01.007}} @article{Eder:1999, Abstract = {Morphological, immunophenotypical and electrophysiological properties were investigated in isolated cultured murine microglia before and after exposure to astrocyte-conditioned medium (ACM). Following application of ACM, microglial cells underwent a dramatic shape transformation from an amoeboid appearance to a ramified morphology. In parallel to morphological changes, a downregulation of macrophage surface antigens was observed in microglia exposed to ACM. Staining intensities for major histocompatibility complex (MHC) class II molecules and for the adhesion molecules leukocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) were significantly decreased in ramified microglia 5 days after exposure to ACM. In microglial cells treated daily with ACM over a period of 5 days, the smallest staining intensities for all surface antigens as well as the smallest ramification index as a measure for the highest degree of ramification were determined. In addition, upregulation of delayed rectifier K + currents was observed in microglia exposed to ACM for 1 day or treated daily with ACM for 5 days. In contrast, untreated amoeboid microglia or ramified microglia analysed 5 days after exposure to ACM did not express delayed rectifier K + currents. Analyses of the resting membrane potential and expression levels and properties of inward rectifier K + currents did not reveal any differences between untreated and ACM-treated microglia. It is suggested that electrophysiological properties of microglia do not strongly correlate with the morphology or the immunophenotype of microglial cells.}, Author = {Eder, C. and Schilling, T. and Heinemann, U. and Haas, D. and Hailer, N. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Cell Differentiation;Animals;Astrocytes;Cells, Cultured;Coculture Techniques;Microglia;Culture Media, Conditioned;11 Glia;Animals, Newborn;Mice, Inbred Strains;Cell Size;Potassium Channels, Voltage-Gated;Potassium Channels;Membrane Potentials;Barium;Delayed Rectifier Potassium Channels;Mice;24 Pubmed search results 2008;Immunohistochemistry;Potassium Channels, Inwardly Rectifying;Cell Adhesion Molecules;Histocompatibility Antigens Class II;Research Support, Non-U.S. Gov't}, Medline = {20062492}, Month = {12}, Nlm_Id = {8918110}, Number = {12}, Organization = {Department of Neurophysiology, Institute of Physiology, Humboldt University, Berlin, Germany. claudia.eder\@charite.de}, Pages = {4251-61}, Pii = {ejn852}, Pubmed = {10594651}, Title = {Morphological, immunophenotypical and electrophysiological properties of resting microglia in vitro}, Uuid = {604EEC69-7FA5-44FD-A8E9-1CC86F2EF3F9}, Volume = {11}, Year = {1999}} @article{Eder:2005, Abstract = {Microglia play an important role in the central nervous system, where these cells, it is believed, have both neuroprotective and neurotoxic effects. In response to acute brain injury or during neurodegenerative and neuroinflammatory diseases, activated microglial cells undergo shape changes, migrate to the affected sites of neuronal damage, proliferate, and release a variety of substances, such as cytokines and reactive oxygen species (ROS). This review summarizes the physiological mechanisms underlying microglial activation and deactivation processes, with particular focus on the involvement of microglial ion channels. Microglial ion channels have been shown to be capable, by regulating membrane potential, cell volume, and intracellular ion concentrations, of modulating or facilitating proliferation, migration, cytokine secretion, shape changes, and the respiratory burst of microglial cells. (c) 2005 Wiley-Liss, Inc.}, Author = {Eder,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {11 Glia}, Month = {5}, Nlm_Id = {7600111}, Number = {3}, Organization = {Institute of Physiology, Humboldt University, Berlin, Germany.}, Pages = {314-321}, Pubmed = {15929071}, Title = {Regulation of microglial behavior by ion channel activity}, Uuid = {3E1C9713-6E2B-468D-9F0F-46F0972F6321}, Volume = {81}, Year = {2005}, url = {papers/Eder_JNeurosciRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20476}} @article{Eder:2001, Abstract = {Microglia, macrophages that reside in the brain, can express at least 12 different ion channels, including voltage-gated proton channels. The properties of H+ currents in microglia are similar to those in other phagocytes. Proton currents are elicited by depolarizing the membrane potential, but activation also depends strongly on both intracellular pH (pH(i)) and extracellular pH (pH(o)). Increasing pH(o) or lowering pH(i) promotes H+ channel opening by shifting the activation threshold to more negative potentials. H+ channels in microglia open only when the pH gradient is outward, so they carry only outward current in the steady state. Time-dependent activation of H+ currents is slow, with a time constant roughly 1 s at room temperature. Microglial H+ currents are inhibited by inorganic polyvalent cations, which reduce H+ current amplitude and shift the voltage dependence of activation to more positive potentials. Cytoskeletal disruptive agents modulate H+ currents in microglia. Cytochalasin D and colchicine decrease the current density and slow the activation of H+ currents. Similar changes of H+ currents, possibly due to cytoskeletal reorganization, occur in microglia during the transformation from ameboid to ramified morphology. Phagocytes, including microglia, undergo a respiratory burst, in which NADPH oxidase releases bactericidal superoxide anions into the phagosome and stoichiometrically releases protons into the cell, tending to depolarize and acidify the cell. H+ currents may help regulate both the membrane potential and pH(i) during the respiratory burst. By compensating for the efflux of electrons and counteracting intracellular acidification, H+ channels help maintain superoxide anion production.}, Author = {Eder, C. and DeCoursey, T. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {Ion Channel Gating;Ion Channels;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, P.H.S.;11 Glia;Microglia;Electrophysiology;Protons;Humans;Animals;Hydrogen-Ion Concentration;review;Brain Chemistry}, Medline = {21137604}, Month = {6}, Nlm_Id = {0370121}, Number = {3}, Organization = {Institut f{\"u}r Physiologie der Charit{\'e}, Humboldt Universit{\"a}t, Tucholskystr. 2, D 10117 Berlin, Germany. claudia.eder\@charite.de}, Pages = {277-305}, Pii = {S0301008200000629}, Pubmed = {11240310}, Title = {Voltage-gated proton channels in microglia}, Uuid = {0B567502-EE2F-11DA-8605-000D9346EC2A}, Volume = {64}, Year = {2001}, url = {papers/Eder_ProgNeurobiol2001.pdf}} @article{Egea:2007, Abstract = {Ephrins are cell-surface tethered guidance cues that bind to Eph receptor tyrosine kinases in trans on opposing cells. In the developing nervous system, the Eph-ephrin signaling system controls a large variety of cellular responses including contact-mediated attraction or repulsion, adhesion or de-adhesion, and migration. Eph-ephrin signaling can be bidirectional, and is subject to modulation by ectodomain cleavage of ephrins and by Eph-ephrin endocytosis. Recent work has highlighted the importance of higher-order clustering of functional Eph-ephrin complexes and the requirement for Rho GTPases as signal transducers. Co-expression of Ephs and ephrins within the same cellular membrane can result in Eph-ephrin cis interaction or in lateral segregation into distinct domains from where they signal opposing effects on the axon.}, Author = {Egea, Joaquim and Klein, R{\"u}diger}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0962-8924}, Journal = {Trends Cell Biol}, Keywords = {10 Development;research support, non-u.s. gov't;Signal Transduction;10 circuit formation;Endocytosis;Ephrins;rho GTP-Binding Proteins;Animals;24 Pubmed search results 2008;review;Axons}, Month = {5}, Nlm_Id = {9200566}, Number = {5}, Organization = {Max-Planck Institute of Neurobiology, D-82152 Martinsried, Germany. jegea\@neuro.mpg.de }, Pages = {230-8}, Pii = {S0962-8924(07)00072-4}, Pubmed = {17420126}, Title = {Bidirectional Eph-ephrin signaling during axon guidance}, Uuid = {6774D901-70BE-4A4B-8CC6-E3BC82745C4D}, Volume = {17}, Year = {2007}, url = {papers/Egea_TrendsCellBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tcb.2007.03.004}} @article{Egensperger:1998, Abstract = {Microglial cells are considered to play an important role in the pathogenesis of Alzheimer disease. Apart from producing the Alzheimer amyloid precursor (APP) as an acute phase protein, microglial cells seem to be involved in the deposition of its amyloidogenic cleavage product, the amyloid-beta peptide (Abeta). Abeta is bound by apolipoprotein E (APOE) in an isoform-specific manner, and it has been demonstrated that inheritance of the AD susceptibility allele, APOE epsilon4, is associated with increased deposition of Abeta in the cerebral cortex. However, the relationship between APOE epsilon4 gene dose and microglial activation is unknown. Using microglial expression of major histocompatibility complex class II molecules as a marker, we have performed a quantitative genotype-phenotype analysis on microglial activation in frontal and temporal cortices of 20 APOE genotyped AD brains. The number of activated microglia and the tissue area occupied by these cells increased significantly with APOE epsilon4 gene dose. When a model of multiple linear regression was used to compare the relative influence of APOE genotype, sex, disease duration, age at death, diffuse and neuritic plaques as well as neurofibrillary tangles on microglial activation, only APOE genotype was found to have a significant effect. Thus, the APOE gene product represents an important determinant of microglial activity in AD. Since microglial activation by APP has been shown to be modulated by apoE in vitro, a direct role of microglia in AD pathogenesis is conceivable.}, Author = {Egensperger, R. and K{\"o}sel, S. and von Eitzen, U. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {1015-6305}, Journal = {Brain Pathol}, Keywords = {Histocompatibility Antigens Class II;Humans;Frontal Lobe;Image Processing, Computer-Assisted;Middle Aged;Immunoenzyme Techniques;Microglia;Female;11 Glia;Male;Aged;Apolipoproteins E;Alzheimer Disease;Linear Models;Temporal Lobe;Senile Plaques;Neurofibrillary Tangles;Research Support, Non-U.S. Gov't}, Medline = {98332358}, Month = {7}, Nlm_Id = {9216781}, Number = {3}, Organization = {Molecular Neuropathology Laboratory, Institute of Neuropathology, Hannover Medical School, Germany.}, Pages = {439-47}, Pubmed = {9669695}, Title = {Microglial activation in Alzheimer disease: Association with APOE genotype}, Uuid = {11359BCB-1C33-4E06-93F8-11A853825610}, Volume = {8}, Year = {1998}} @article{Eggan:2004, Abstract = {Cloning by nuclear transplantation has been successfully carried out in various mammals, including mice. Until now mice have not been cloned from post-mitotic cells such as neurons. Here, we have generated fertile mouse clones derived by transferring the nuclei of post-mitotic, olfactory sensory neurons into oocytes. These results indicate that the genome of a post-mitotic, terminally differentiated neuron can re-enter the cell cycle and be reprogrammed to a state of totipotency after nuclear transfer. Moreover, the pattern of odorant receptor gene expression and the organization of odorant receptor genes in cloned mice was indistinguishable from wild-type animals, indicating that irreversible changes to the DNA of olfactory neurons do not accompany receptor gene choice.}, Author = {Eggan, Kevin and Baldwin, Kristin and Tackett, Michael and Osborne, Joseph and Gogos, Joseph and Chess, Andrew and Axel, Richard and Jaenisch, Rudolf}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Embryo;Gene Expression Regulation, Developmental;Research Support, Non-U.S. Gov't;Totipotent Stem Cells;Embryonic and Fetal Development;Olfactory Receptor Neurons;Research Support, U.S. Gov't, P.H.S.;Oocytes;Cloning, Organism;22 Stem cells;Animals;Receptors, Odorant;Cell Nucleus;Mice;Polyploidy}, Month = {3}, Nlm_Id = {0410462}, Number = {6978}, Organization = {Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA.}, Pages = {44-9}, Pii = {nature02375}, Pubmed = {14990966}, Title = {Mice cloned from olfactory sensory neurons}, Uuid = {35D6617F-E354-42DE-A4D7-98D6549C826E}, Volume = {428}, Year = {2004}, url = {papers/Eggan_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature02375}} @article{Eggan:2000, Abstract = {To study whether cloning resets the epigenetic differences between the two X chromosomes of a somatic female nucleus, we monitored X inactivation in cloned mouse embryos. Both X chromosomes were active during cleavage of cloned embryos, followed by random X inactivation in the embryo proper. In the trophectoderm (TE), X inactivation was nonrandom with the inactivated X of the somatic donor being chosen for inactivation. When female embryonic stem cells with two active X chromosomes were used as donors, random X inactivation was seen in the TE and embryo. These results demonstrate that epigenetic marks can be removed and reestablished on either X chromosome during cloning. Our results also suggest that the epigenetic marks imposed on the X chromosomes during gametogenesis, responsible for normal imprinted X inactivation in the TE, are functionally equivalent to the marks imposed on the chromosomes during somatic X inactivation.}, Author = {Eggan, K. and Akutsu, H. and Hochedlinger, K. and Rideout, W. and Yanagimachi, R. and Jaenisch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Transgenes;Research Support, Non-U.S. Gov't;Cell Differentiation;Placenta;Animals;Stem Cell Transplantation;Female;Oocytes;Cloning, Organism;Green Fluorescent Proteins;Embryonic and Fetal Development;Embryo;Reverse Transcriptase Polymerase Chain Reaction;Muridae;Research Support, U.S. Gov't, P.H.S.;Male;Alleles;X Chromosome;Gene Silencing;Cell Nucleus;Mice;22 Stem cells;Luminescent Proteins;Stem Cells;Genes, Reporter;Dosage Compensation, Genetic;Genomic Imprinting}, Medline = {20545826}, Month = {11}, Nlm_Id = {0404511}, Number = {5496}, Organization = {Whitehead Institute for Biomedical Research and Department of Biology, Massachusetts Institute of Technology, 9 Cambridge Center, Cambridge, MA 02142, USA.}, Pages = {1578-81}, Pii = {9012}, Pubmed = {11090356}, Title = {X-Chromosome inactivation in cloned mouse embryos}, Uuid = {0FD6F8F1-C84F-4B8A-A7A1-39552A60064B}, Volume = {290}, Year = {2000}} @article{Egger:2003, Abstract = {Granule cells are axonless local interneurons that mediate lateral inhibitory interactions between the principal neurons of the olfactory bulb via dendrodendritic reciprocal synapses. This unusual arrangement may give rise to functional properties different from conventional lateral inhibition. Although granule cells spike, little is known about the role of the action potential with respect to their synaptic output. To investigate the signals that underlie dendritic release in these cells, two-photon microscopy in rat brain slices was used to image calcium transients in granule cell dendrites and spines. Action potentials evoked calcium transients throughout the dendrites, with amplitudes increasing with distance from soma and attaining a plateau level within the external plexiform layer, the zone of granule cell synaptic output. Transient amplitudes were, on average, equal in size in spines and adjacent dendrites. Surprisingly, both spine and dendritic amplitudes were strongly dependent on membrane potential, decreasing with depolarization and increasing with hyperpolarization from rest. Both the current-voltage relationship and the time course of inactivation were consistent with the known properties of T-type calcium channels, and the voltage dependence was blocked by application of the T-type calcium channel antagonists Ni2+ and mibefradil. In addition, mibefradil reduced action potential-mediated synaptic transmission from granule to mitral cells. The implication of a transiently inactivating calcium channel in synaptic release from granule cells suggests novel mechanisms for the regulation of lateral inhibition in the olfactory bulb. 1529-2401 Journal Article}, Author = {Egger, V. and Svoboda, K. and Mainen, Z. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurosci}, Keywords = {13 Olfactory bulb anatomy;Calcium/*metabolism;Animals;Cells, Cultured;Rats;Dendrites/metabolism;Synaptic Transmission;Calcium Channels, T-Type/physiology;Rats, Sprague-Dawley;Kinetics;Ion Transport;Olfactory Bulb/*cytology/metabolism/*physiology;*Neural Inhibition;Support, Non-U.S. Gov't;Interneurons/cytology/*metabolism/physiology;Support, U.S. Gov't, P.H.S.;Membrane Potentials;I pdf;*Action Potentials}, Number = {20}, Organization = {Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. egger\@cshl.edu}, Pages = {7551-8}, Pubmed = {12930793}, Title = {Mechanisms of lateral inhibition in the olfactory bulb: efficiency and modulation of spike-evoked calcium influx into granule cells}, Uuid = {13897D52-EF1C-4BA2-9316-A644F10C970F}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12930793}} @article{Eglitis:1997, Abstract = {Glial cells are thought to derive embryologically from either myeloid cells of the hematopoietic system (microglia) or neuroepithelial progenitor cells (astroglia and oligodendrocytes). However, it is unclear whether the glia in adult brains free of disease or injury originate solely from cells present in the brain since the fetal stage of development, or if there is further input into such adult brains from cells originating outside the central nervous system. To test the ability of hematopoietic cells to contribute to the central nervous system, we have transplanted adult female mice with donor bone marrow cells genetically marked either with a retroviral tag or by using male donor cells. Using in situ hybridization histochemistry, a continuing influx of hematopoietic cells into the brain was detected. Marrow-derived cells were already detected in the brains of mice 3 days after transplant, and their numbers increased over the next several weeks, exceeding 14,000 cells per brain in several animals. Marrow-derived cells were widely distributed throughout the brain, including the cortex, hippocampus, thalamus, brain stem, and cerebellum. When in situ hybridization histochemistry was combined with immunohistochemical staining using lineage-specific markers, some bone marrow-derived cells were positive for the microglial antigenic marker F4/80. Other marrow-derived cells surprisingly expressed the astroglial marker glial fibrillary acidic protein. These results indicate that some microglia and astroglia arise from a precursor that is a normal constituent of adult bone marrow.}, Author = {Eglitis, M. A. and Mezey, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {In Situ Hybridization;Gene Transfer Techniques;Cell Differentiation;Neuroglia;Hematopoietic Stem Cells;Female;Mice, Inbred C57BL;Genetic Markers;11 Glia;Microglia;Hematopoietic Stem Cell Transplantation;Animals;Mice;Male}, Medline = {97268700}, Month = {4}, Nlm_Id = {7505876}, Number = {8}, Organization = {Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892, USA.}, Pages = {4080-5}, Pubmed = {9108108}, Title = {Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice}, Uuid = {8481D91C-D3B7-11D9-A0E9-000D9346EC2A}, Volume = {94}, Year = {1997}} @article{Ehlers:2007, Abstract = {Dendrites and axons exhibit different morphologies and patterns of growth. This difference in neuronal structure is controlled by evolutionarily conserved directed trafficking through the secretory pathway.}, Author = {Ehlers, Michael D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cell Differentiation;Dendrites;Central Nervous System;21 Neurophysiology;Golgi Apparatus;Neurosecretion;Protein Transport;Nerve Tissue Proteins;Cell Enlargement;Endoplasmic Reticulum;Signal Transduction;Animals;Humans;24 Pubmed search results 2008;news}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Howard Hughes Medical Institute, Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. ehlers\@neuro.duke.edu}, Pages = {686-9}, Pii = {S0896-6273(07)00621-6}, Pubmed = {17785176}, Title = {Secrets of the secretory pathway in dendrite growth}, Uuid = {748DFF65-3050-4119-8EAF-C2FC9E686517}, Volume = {55}, Year = {2007}, url = {papers/Ehlers_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.08.009}} @article{Ehninger:2003, Abstract = {We here report that voluntary wheel running led to a regional increase in the number of newly generated cortical microglia. We asked how adult cortical cell genesis would respond to environmental enrichment and physical activity, both stimuli that robustly induce adult hippocampal neurogenesis. After labeling proliferating cells with bromodeoxyuridine (BrdU) and immunohistochemical detection of BrdU, we found that both experimental paradigms did not result in general effects on cell proliferation and cell genesis in the neocortex. However, there were regionally and layer specific changes in the number of BrdU marked cells, both 1 day and 4 weeks after BrdU. Environmental enrichment led to a significant increase in the number of new astrocytes in layer 1 of the motor cortex. Voluntary wheel running, in contrast, caused an induction in the proliferation of microglia in superficial cortical layers of several brain regions. Under no condition was the number of new oligodendrocytes measurably enhanced. In contrast to the hippocampus, we did not find any new neurons in the cortex. The physiological 'activation' of microglia adds a new aspect to the question of microglial function in the healthy brain and of how adult brain cells can plastically react to physiological stimuli.}, Author = {Ehninger, Dan and Kempermann, Gerd}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {01 Adult neurogenesis general;Female;Environment;Cell Division;Neocortex;11 Glia;Microglia;Motor Activity;Mice, Inbred C57BL;06 Adult neurogenesis injury induced;Mice;Animals;Support, Non-U.S. Gov't}, Medline = {22737282}, Month = {8}, Nlm_Id = {9110718}, Number = {8}, Organization = {Max Delbr{\"u}ck Center for Molecular Medicine (MDC), Berlin-Buch, Robert-R{\"o}ssle-Strasse 10, 13125 Berlin.}, Pages = {845-51}, Pubmed = {12853371}, Title = {Regional effects of wheel running and environmental enrichment on cell genesis and microglia proliferation in the adult murine neocortex}, Uuid = {47FF837A-4296-11DB-A5D2-000D9346EC2A}, Volume = {13}, Year = {2003}, url = {papers/Ehninger_CerebCortex2003.pdf}} @article{Ehring:2003, Abstract = {BACKGROUND: An optimal system for the expansion of pluripotent HPCs would ideally eliminate the use of cytokines and animal-derived serum. We have shown previously that a 3D, tantalum-coated porous biomaterial (Cytomatrix) supports the maintenance and expansion of human BM HPCs in the absence of cytokines. METHODS: Umbilical cord blood (UCB) derived HPC were cultured in the Cytomatrix in the absence of exogenous cytokines. Phenotype was determined using FACS. Colony-forming units (CFU) activity was evaluated. Engraftment capacity was evaluated by transplanting the expanded cells into non-obese diabetic (NOD)/SCID mice. RESULTS: We describe the expansion of HPCs from UCB using the Cytomatrix system. When UCB-derived CD34(+) cells were cultured in the Cytomatrix system for 2 weeks we observed an increase in the number of nucleated cells (3-fold) and CFU (2.6-fold). The number of CD45(+) and CD34(+) cells both increased three-fold. Trends demonstrated an increase in the frequency of CD34(+)C38(-) cells, and an increase in both CD34(+)C33(+) cells and CD34(+)C61(+) cells. No expansion of T or B lymphocytes was observed. When expanded UCB cells from the Cytomatrix were injected into sub-lethally irradiated NOD/SCID mice, human cells were detected in the murine peripheral blood and BM 6 weeks post-transplantation. DISCUSSION: This unique approach to the expansion of UCB cells in a serum-free, cytokine-free environment may provide expansion of HPCs with multi-lineage engraftment capability that could be used clinically.}, Author = {Ehring, B. and Biber, K. and Upton, T. M. and Plosky, D. and Pykett, M. and Rosenzweig, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1465-3249}, Journal = {Cytotherapy}, Keywords = {Mice, SCID;Antigens, CD45;Animals;Flow Cytometry;Receptors, CXCR4;Integrin beta3;ADP-ribosyl Cyclase;Cell Count;Cell Division;Antigens, CD;Hematopoietic Stem Cells;Research Support, U.S. Gov't, Non-P.H.S.;Antigens, CD3;Antigens, Differentiation, Myelomonocytic;Macrophages;Granulocytes;Transplantation, Heterologous;11 Glia;Hematopoietic Stem Cell Transplantation;Coated Materials, Biocompatible;Antigens, CD19;Fetal Blood;Integrin alpha4beta1;Antigens, CD34;Mice, Inbred NOD;Colony-Forming Units Assay;Bone Marrow Cells;Mice;Cell Culture Techniques;Humans}, Nlm_Id = {100895309}, Number = {6}, Organization = {Cytomatrix, Woburn, MA 01801, USA.}, Pages = {490-9}, Pii = {4K0GEY9DGFC1EAGM}, Pubmed = {14660045}, Title = {Expansion of HPCs from cord blood in a novel 3D matrix}, Uuid = {42B8FF9D-377A-446C-845B-563E002076EF}, Volume = {5}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/14653240310003585}} @article{Eichhoff:2008, Abstract = {PURPOSE: Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. METHODS: In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. RESULTS: We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the "aging pigment" lipofuscin. CONCLUSIONS: Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease.}, Author = {Eichhoff, and Busche, and Garaschuk,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1619-7070}, Journal = {Eur J Nucl Med Mol Imaging}, Keywords = {21 Neurophysiology;21 Calcium imaging;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {101140988}, Organization = {Institute of Neuroscience, Technical University of Munich, Biedersteinerstr. 29, 80802, Munich, Germany, olga.garaschuk\@lrz.tum.de.}, Pubmed = {18193219}, Title = {In vivo calcium imaging of the aging and diseased brain}, Uuid = {55FE76AA-34C2-44D6-9435-515179756E74}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00259-007-0709-6}} @article{Eidelman:1984, Abstract = {Purified G-protein from vesicular stomatitis virus was reconstituted into egg phosphatidylcholine vesicles by detergent dialysis of octyl glucoside. A homogeneous population of reconstituted vesicles could be obtained, provided the protein to lipid ratio was high (about 0.3 mol \%protein) and the detergent removal was slow. The reconstituted vesicles were assayed for fusion activity using electron microscopy and fluorescence energy transfer. The fusion activity mediated by the viral envelope protein was dependent upon pH, temperature, and target membrane lipid composition. Incubation of reconstituted vesicles at low pH with small unilamellar vesicles containing negatively charged lipids resulted in the appearance of large cochleate structures, as shown by electron microscopy using negative stain. This process did not cause leakage of a vesicle-encapsulated aqueous marker. The rate of fusion was pH-dependent with a pK of about 4 and the apparent energy of activation for the fusion was 16 +/- 1 kcal/mol. G-protein-mediated fusion showed a large preference for target membranes which contain phosphatidylserine or phosphatidic acid. Inclusion of 36\%cholesterol in any of the lipid compositions had no effect on the rate of fusion. These reconstituted vesicles provide a system to study the mechanism of pH-dependent fusion induced by a viral spike protein.}, Author = {Eidelman, O. and Schlegel, R. and Tralka, T. S. and Blumenthal, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {24 Pubmed search results 2008;Membrane Glycoproteins;Research Support, Non-U.S. Gov't;Kinetics;Microscopy, Electron;Liposomes;Cell Line;Cercopithecus aethiops;Viral Proteins;Vesicular stomatitis-Indiana virus;Glucosides;Phosphatidylcholines;Animals;Hydrogen-Ion Concentration;Kidney;Viral Envelope Proteins;15 Retrovirus mechanism}, Medline = {84162177}, Month = {4}, Nlm_Id = {2985121R}, Number = {7}, Pages = {4622-8}, Pubmed = {6323480}, Title = {pH-dependent fusion induced by vesicular stomatitis virus glycoprotein reconstituted into phospholipid vesicles}, Uuid = {68302A7A-EE2C-11DA-8605-000D9346EC2A}, Volume = {259}, Year = {1984}} @article{Eilers:2001, Abstract = {1. Cellular responses to GABA(A) receptor activation were studied in developing cerebellar Purkinje neurones (PNs) in brain slices obtained from 2- to 22-day-old rats. Two-photon fluorescence imaging of fura-2-loaded cells and perforated-patch recordings were used to monitor intracellular Ca2+ transients and to estimate the reversal potential of GABA-induced currents, respectively. 2. During the 1st postnatal week, focal application of GABA or the GABA(A) receptor agonist muscimol evoked transient increases in [Ca2+]i in immature PNs. These Ca2+ transients were reversibly abolished by the GABA(A) receptor antagonist bicuculline and by Ni2+, a blocker of voltage-activated Ca2+ channels. 3. Perforated-patch recordings were used to measure the reversal potential of GABA-evoked currents (E(GABA)) at different stages of development. It was found that E(GABA) was about -44 mV at postnatal day 3 (P3), it shifted to gradually more negative values during the 1st week and finally equilibrated at -87 mV at around the end of the 2nd postnatal week. This transition was well described by a sigmoidal function. The largest change in E(GABA) was -7 mV x day(-1), which occurred at around P6. 4. The transition in GABA-mediated signalling occurs during a period in which striking changes in PN morphology and synaptic connectivity are known to take place. Since such changes were shown to be Ca2+ dependent, we propose that GABA-evoked Ca2+ signalling is one of the critical determinants for the normal development of cerebellar PNs.}, Author = {Eilers, J. and Plant, T. D. and Marandi, N. and Konnerth, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {gamma-Aminobutyric Acid;Purkinje Cells;Calcium Signaling;Animals;Rats;Patch-Clamp Techniques;Nickel;Rats, Wistar;Calcium;Bicuculline;research support, non-u.s. gov't ;Receptors, GABA-A;21 Neurophysiology;Membrane Potentials;GABA Antagonists;Cerebellum;Anti-Bacterial Agents;24 Pubmed search results 2008;Gramicidin;Research Support, Non-U.S. Gov't}, Medline = {21486753}, Month = {10}, Nlm_Id = {0266262}, Number = {Pt 2}, Organization = {Abteilung Neurophysiologie, Max-Planck-Institut f{\"u}r Hirnforschung, 60528 Frankfurt, Germany. eilers\@mpih-frankfurt.mpg.de}, Pages = {429-37}, Pii = {PHY_12525}, Pubmed = {11600678}, Title = {GABA-mediated Ca2+ signalling in developing rat cerebellar Purkinje neurones}, Uuid = {5661E981-27D4-4629-802D-E84B2F2CBC5C}, Volume = {536}, Year = {2001}} @article{Ekdahl:2001, Abstract = {The dentate gyrus (DG) is one of the few regions in the brain that continues to produce new neurons throughout adulthood. Seizures not only increase neurogenesis, but also lead to death of DG neurons. We investigated the relationship between cell death and neurogenesis following seizures in the DG of adult rats by blocking caspases, which are key components of apoptotic cell death. Multiple intracerebroventricular infusions of caspase inhibitors (pancaspase inhibitor zVADfmk, and caspase 3 and 9 inhibitor) prior to, just after, 1 day after, and 1 week following 2 h of lithium-pilocarpine-induced status epilepticus reduced the number of terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick-end labelled (TUNEL) cells and increased the number of bromodeoxyuridine (BrdU) -stained proliferated cells in the subgranular zone at 1 week. The caspase inhibitor-treated group did not differ from control at 2 days or 5 weeks following the epileptic insult. Our findings suggest that caspases modulate seizure-induced neurogenesis in the DG, probably by regulating apoptosis of newly born neurons, and that this action can be suppressed transiently by caspase inhibitors. Furthermore, although previous studies have indicated that increased neuronal death can trigger neurogenesis, we show here that reduction in apoptotic death may be associated with increased neurogenesis.}, Author = {Ekdahl, C. T. and Mohapel, P. and Elmer, E. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {Eur J Neurosci}, Keywords = {06 Adult neurogenesis injury induced;D pdf}, Number = {6}, Organization = {Section of Restorative Neurology, Wallenberg Neuroscience Center, BMC A11, SE-221 84 Lund, Sweden; Section of Experimental Brain Research, Wallenberg Neuroscience Center, BMC A13, SE-221 84 Lund, Sweden.}, Pages = {937-45.}, Title = {Caspase inhibitors increase short-term survival of progenitor-cell progeny in the adult rat dentate gyrus following status epilepticus}, Uuid = {44A1F12E-393A-4C39-8495-F4D1CC64EB6C}, Volume = {14}, Year = {2001}, url = {papers/Ekdahl_EurJNeurosci2001}} @article{Ekdahl:2003, Abstract = {New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation. 0027-8424 Journal Article}, Author = {Ekdahl, C. T. and Claasen, J. H. and Bonde, S. and Kokaia, Z. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Hippocampus/metabolism;Neurons/*physiology;Animals;*Inflammation;Bromodeoxyuridine/pharmacology;Rats;Microglia/metabolism;D pdf;Rats, Sprague-Dawley;Minocycline/pharmacology;Lipopolysaccharides/metabolism/pharmacology;Male;Support, Non-U.S. Gov't;Anti-Bacterial Agents/pharmacology;Antimetabolites/pharmacology;06 Adult neurogenesis injury induced;Brain/*metabolism;Immunohistochemistry}, Number = {23}, Organization = {Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, Biomedical Center A-11, Lund, Sweden.}, Pages = {13632-7}, Title = {Inflammation is detrimental for neurogenesis in adult brain}, Uuid = {D7A5FFDD-B724-49AD-9C19-F5627372966F}, Volume = {100}, Year = {2003}, url = {papers/Ekdahl_ProcNatlAcadSciUSA2003.pdf}} @article{Ekstrand:1996, Abstract = {A non-radioactive 96-well microtitre plate reverse transcriptase (RT) assay, based on the use of covalently bound riboadenosine homopolymer in the wells and 5-bromodeoxyuridined 5'-triphosphate (BrdUTP) as dNTP, is described. The whole assay is performed in a single well, including the quantitative detection of incorporated BrdU, which is performed immunologically using alkaline phosphatase-conjugated anti-BrdU antibody and colorometric reading. The system also allows the use of variable amounts of primer. The kinetics and characteristics of the assay using BrdUTP is similar to the use of [3H]dTTP. The sensitivity of the assay can be varied either by altering the duration of RT assay time and/or by prolonging the alkaline phosphatase reaction. Thus the assay can detect < 0.02 pg of recombinant human-immunodeficiency-virus (HIV) type I RT, < 0.005 m unit of avian-myeloblastosis-virus RT or < 0.02 m unit of recombinant Moloney-murine-leukaemia-virus RT. The assay was found to be useful with various types of cell-culture material, and a comparative study of 16 HIV-infected lymphocyte cultures, using 10 microliters of supernatant medium for RT assay and 22.5 microliters for p24 antigen assay showed that the new RT assay was at least 25-fold more sensitive than the p24 antigen assay. The results also show a good correlation between the RT activities found and the p24-antigen level detected, with exception for HIV2 isolates, as they only became positive in the RT assay. The technical performance and the capacity of the test compared with other available RT kits is discussed, as well as its use for other applications.}, Author = {Ekstrand, D. H. and Awad, R. J. and K{\"a}llander, C. F. and Gronowitz, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0885-4513}, Journal = {Biotechnol Appl Biochem}, Keywords = {Thymine Nucleotides;Reference Standards;Titrimetry;RNA-Directed DNA Polymerase;HIV Infections;Research Support, Non-U.S. Gov't;Deoxyuracil Nucleotides;DNA;Subcellular Fractions;Sensitivity and Specificity;15 Retrovirus mechanism;Humans;HIV;Cells, Cultured;Templates, Genetic;24 Pubmed search results 2008}, Medline = {96206778}, Month = {4}, Nlm_Id = {8609465}, Organization = {Department of Medical Genetics, Uppsala University, Sweden.}, Pages = {95-105}, Pubmed = {8639277}, Title = {A sensitive assay for the quantification of reverse transcriptase activity based on the use of carrier-bound template and non-radioactive-product detection, with special reference to human-immunodeficiency-virus isolation}, Uuid = {3CAB3E90-F035-426D-9260-48A8AF34429C}, Volume = {23 ( Pt 2)}, Year = {1996}} @article{El-Maarouf:2006, Abstract = {Polysialic acid (PSA), a large cell-surface carbohydrate that regulates cell interactions, is used during vertebrate development to promote precursor cell migration and axon path-finding. The induction of PSA expression in damaged adult CNS tissues could help them to rebuild by creating conditions permissive for architectural remodeling. This possibility has been explored in two contexts, the regeneration of axons and the recruitment of endogenous neural precursors to a lesion. Glial scars that form at CNS injury sites block axon regeneration. It has been found that transfection of scar astrocytes by a viral vector encoding polysialyltransferase leads to sustained expression of high levels of PSA. With this treatment, a substantial portion of severed corticospinal tract axon processes were able to grow through a spinal injury site. In the studies of precursor cell migration to a cortical lesion, it was found that induced PSA expression in a path extending from the subventricular zone to a lesion near the cortical surface increased recruitment of BrdU/nestin-positive cells along the path and into the injury site. These displaced precursors were able to differentiate in a regionally appropriate manner. These findings suggest that induced PSA expression can be used as a strategy for promoting tissue repair involving both replacement of cells and rebuilding of neural connections.}, Author = {El Maarouf, Abderrahman and Petridis, Athanasios K. and Rutishauser, Urs}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Mice;Sialic Acids;Transfection;24 Pubmed search results 2008;Central Nervous System;Nerve Regeneration;Sialyltransferases;Astrocytes;Recombinant Proteins;Stem Cells;Mice, Transgenic;Animals;Cell Movement;Male;Brain Injuries;Axons}, Month = {11}, Nlm_Id = {7505876}, Number = {45}, Organization = {Laboratory of Cellular and Developmental Neuroscience, Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. a-el-maarouf\@ski.mskcc.org}, Pages = {16989-94}, Pii = {0608036103}, Pubmed = {17075041}, Title = {Use of polysialic acid in repair of the central nervous system}, Uuid = {1AC1BB78-AB09-481E-8887-BFE7D5CF8CF2}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0608036103}} @article{ElShamy:1998, Abstract = {More than half of the dorsal root ganglion (DRG) neurons are lost by excessive cell death coinciding with precursor proliferation and cell cycle exit in neurotrophin-3 null mutant (NT-3-/-) mice. We find that in the absence of NT-3, sensory precursor cells fail to arrest the cell cycle, override the G1 phase restriction point, and die by apoptosis in S phase, which can be prevented in vivo by a cell cycle blocker. Uncoordinated cell cycle reentry is preceded by a failure of nuclear N-myc downregulation and is paralleled by the activation of the full repertoire of G1 and S phase cell cycle proteins required for cell cycle entry. Our results provide evidence for novel activity of neurotrophins in cell cycle control and point toward an N-myc sensitization to cell death in the nervous system that is under the control of NT-3. 0896-6273 Journal Article}, Author = {ElShamy, W. M. and Fridvall, L. K. and Ernfors, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {Neuron}, Keywords = {Neurotrophin 3;EE pdf;Mice, Inbred BALB C;Mice, Knockout;Nerve Growth Factors/*deficiency/*genetics;Cell Division/genetics;Neurons, Afferent/*pathology;08 Aberrant cell cycle;G1 Phase/*genetics;Animals;Support, Non-U.S. Gov't;Mice;S Phase/*genetics;Stem Cells/*pathology}, Number = {5}, Organization = {Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.}, Pages = {1003-15}, Pubmed = {9856457}, Title = {Growth arrest failure, G1 restriction point override, and S phase death of sensory precursor cells in the absence of neurotrophin-3}, Uuid = {ED2AF5FF-B3D0-4632-8AF4-2A38059275FC}, Volume = {21}, Year = {1998}, url = {papers/ElShamy_Neuron1998.pdf}} @article{Elias:2007, Abstract = {Radial glia, the neuronal stem cells of the embryonic cerebral cortex, reside deep within the developing brain and extend radial fibres to the pial surface, along which embryonic neurons migrate to reach the cortical plate. Here we show that the gap junction subunits connexin 26 (Cx26) and connexin 43 (Cx43) are expressed at the contact points between radial fibres and migrating neurons, and acute downregulation of Cx26 or Cx43 impairs the migration of neurons to the cortical plate. Unexpectedly, gap junctions do not mediate neuronal migration by acting in the classical manner to provide an aqueous channel for cell-cell communication. Instead, gap junctions provide dynamic adhesive contacts that interact with the internal cytoskeleton to enable leading process stabilization along radial fibres as well as the subsequent translocation of the nucleus. These results indicate that gap junction adhesions are necessary for glial-guided neuronal migration, raising the possibility that the adhesive properties of gap junctions may have an important role in other physiological processes and diseases associated with gap junction function.}, Author = {Elias, Laura A. B. and Wang, Doris D. and Kriegstein, Arnold R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Gap Junctions;research support, non-u.s. gov't;Cell Adhesion;Rats, Sprague-Dawley;Rats;Gene Expression Regulation;Neocortex;research support, n.i.h., extramural;Connexin 43;Animals;Cell Movement;Connexins;Neurons;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0410462}, Number = {7156}, Organization = {Neuroscience Graduate Program, University of California San Francisco, 513 Parnassus Avenue, San Francisco, California 94143, USA. EliasL\@stemcell.ucsf.edu}, Pages = {901-7}, Pii = {nature06063}, Pubmed = {17713529}, Title = {Gap junction adhesion is necessary for radial migration in the neocortex}, Uuid = {74F7A21E-43F8-432B-8A34-92B102A01079}, Volume = {448}, Year = {2007}, url = {papers/Elias_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06063}} @article{Eliopoulos:2002, Abstract = {Naturally occurring drug resistance genes of human origin can be exploited for selection of genetically engineered cells co-expressing a desired therapeutic transgene. Their non-immunogenicity in clinical applications would be a major asset. Human cytidine deaminase (hCD) is a chemoresistance gene that inactivates cytotoxic cytosine nucleoside analogs, such as cytosine arabinoside (Ara-C). The aim of this study was to establish if the hCD gene can serve as an ex vivo dominant selectable marker in engineered bone marrow stromal cells (MSCs). A bicistronic retrovector comprising the hCD cDNA and the green fluorescent protein (GFP) reporter gene was generated and used for transduction of A549 cells and primary murine MSCs. Analysis of transduced cells demonstrated stable integration of proviral DNA, more than 1000-fold increase in CD enzyme activity, and drug resistance to cytosine nucleoside analogs. In a mixture of transduced and untransduced MSCs, the percentage of retrovector-expressing cells could be increased to virtual purity (>99.5\%) through in vitro drug selection with 1 microM Ara-C. Increased selective pressure with 2.5 microM Ara-C allowed for enrichment of a mixed population of MSCs expressing approximately six-fold higher levels of GFP and of CD activity when compared with unmanipulated engineered MSCs. Moreover, engraftment and endothelial differentiation of these in vitro selected and enriched gene-modified marrow stromal cells was demonstrated by Matrigel assay in vivo. In conclusion, these findings outline the potential of human CD as an ex vivo selection and enrichment marker of genetically engineered MSCs for transgenic cell therapy applications.}, Author = {Eliopoulos, N. and Al-Khaldi, A. and Beaus{\'e}jour, C. M. and Momparler, R. L. and Momparler, L. F. and Galipeau, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Transduction, Genetic;Cytidine Deaminase;Humans;Animals;Cell Separation;Antimetabolites, Antineoplastic;Female;Neoplasms;Mice, Inbred C57BL;Retroviridae;11 Glia;Green Fluorescent Proteins;Genetic Vectors;Bone Marrow Cells;Cytarabine;Gene Therapy;Tumor Cells, Cultured;Mice;Drug Resistance;Biological Markers;Luminescent Proteins;Stromal Cells;Research Support, Non-U.S. Gov't}, Medline = {21935229}, Month = {4}, Nlm_Id = {9421525}, Number = {7}, Organization = {Lady Davis Institute for Medical Research, Department of Experimental Medicine, McGill University, Montreal, Canada.}, Pages = {452-62}, Pubmed = {11938460}, Title = {Human cytidine deaminase as an ex vivo drug selectable marker in gene-modified primary bone marrow stromal cells}, Uuid = {4D3B7275-F873-4EB8-8E96-48B2CF717790}, Volume = {9}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301675}} @article{Eljaschewitsch:2006, Abstract = {Endocannabinoids are released after brain injury and believed to attenuate neuronal damage by binding to CB(1) receptors and protecting against excitotoxicity. Such excitotoxic brain lesions initially result in primary destruction of brain parenchyma, which attracts macrophages and microglia. These inflammatory cells release toxic cytokines and free radicals, resulting in secondary neuronal damage. In this study, we show that the endocannabinoid system is highly activated during CNS inflammation and that the endocannabinoid anandamide (AEA) protects neurons from inflammatory damage by CB(1/2) receptor-mediated rapid induction of mitogen-activated protein kinase phosphatase-1 (MKP-1) in microglial cells associated with histone H3 phoshorylation of the mkp-1 gene sequence. As a result, AEA-induced rapid MKP-1 expression switches off MAPK signal transduction in microglial cells activated by stimulation of pattern recognition receptors. The release of AEA in injured CNS tissue might therefore represent a new mechanism of neuro-immune communication during CNS injury, which controls and limits immune response after primary CNS damage.}, Author = {Eljaschewitsch, Eva and Witting, Anke and Mawrin, Christian and Lee, Thomas and Schmidt, Peter M. and Wolf, Susanne and Hoertnagl, Heide and Raine, Cedric S. and Schneider-Stock, Regine and Nitsch, Robert and Ullrich, Oliver}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {07 Excitotoxicity Apoptosis;11 Glia}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Institute of Immunology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany.}, Pages = {67-79}, Pii = {S0896-6273(05)01008-1}, Pubmed = {16387640}, Title = {The Endocannabinoid Anandamide Protects Neurons during CNS Inflammation by Induction of MKP-1 in Microglial Cells}, Uuid = {AC0F123B-3A45-4B66-A202-48619007A505}, Volume = {49}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.11.027}} @article{Elliot:1981, Abstract = {Nerve injury that severs axons also disrupts ensheathing glial cells. Specifically, crushing or cutting the leech nerve cord separates the glial cell's nucleated portion from an anucleate recording, by intracellular injection of Lucifer Yellow dye and horseradish peroxidase (HRP) as tracers, and by electron microscopy. The nucleated portion of the glial cell did not divide, degenerate, or grow appreciably. The severed glial stump remained isolated from the nucleated portion but maintained its resting potential and normal morphology for months. Stumps typically began to deteriorate after 3 months. Small macrophage-like cells, or 'microglia' increased in number after injury and ensheathed axons, thus partially replacing the atrophying glial stump. Some axons in the nerve cord degenerated; the remainder appeared morphologically and physiologically normal. Thus, both nucleated and anucleate glial segments persisted throughout the one to two months required for axons to regenerate functional connections. Glial cells in the leech are therefore available to guide physically the growing axons or to contribute in other ways to nerve regeneration.}, Author = {Elliot, E. J. and Muller, K. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Neuroglia;Nerve Regeneration;Microscopy, Electron;Research Support, U.S. Gov't, P.H.S.;Leeches;11 Glia;Immunoenzyme Techniques;Animals;24 Pubmed search results 2008;Axons}, Medline = {82001443}, Month = {8}, Nlm_Id = {0045503}, Number = {1-2}, Pages = {99-113}, Pubmed = {7023608}, Title = {Long-term survival of glial segments during nerve regeneration in the leech}, Uuid = {D70A0965-8D59-4AE2-A4EC-F5F375183090}, Volume = {218}, Year = {1981}} @article{Elliott:2008, Abstract = {During embryonic development, large numbers of apoptotic cells are rapidly cleared by phagocytes. In this issue, Kurant et al. (2008) describe a new phagocytic receptor, called six-microns-under (SIMU), that promotes engulfment of apoptotic neurons by glial cells in the developing nervous system of Drosophila.}, Author = {Elliott, Michael R. and Ravichandran, Kodi S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {Neuroglia;Central Nervous System;Membrane Proteins;Apoptosis;Drosophila Proteins;Drosophila;comment;Animals;Phagocytosis;Neurons;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0413066}, Number = {3}, Organization = {Carter Immunology Center and the Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.}, Pages = {393-5}, Pii = {S0092-8674(08)00505-9}, Pubmed = {18455977}, Title = {Death in the CNS: six-microns-under}, Uuid = {73346BAF-FEA0-47BD-95FB-57CCB3663DA9}, Volume = {133}, Year = {2008}, url = {papers/Elliott_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.04.014}} @article{Elliott:2001, Abstract = {In various chemoconvulsant models of human temporal lobe epilepsy, the induction of epileptogenesis by a prolonged period of continuous seizure activity is accompanied by significant changes in hippocampal structure. These changes include an increase in neurogenesis within the proliferative subgranular zone (SGZ) of the dentate gyrus and induction of mossy fiber sprouting in mature dentate granule cells. As dentate granule cell neurogenesis and axon outgrowth are also hallmarks of hippocampal development, we hypothesized that molecules involved in normal development may also play a role in similar changes associated with epileptogenesis. To begin to test this hypothesis, we have analyzed the expression patterns of multiple members of the basic helix- loop-helix (bHLH) family of transcription factors in both normal and epileptic adult rats. bHLH protein expression has been found recently in dentate granule cells at specific developmental stages, and analysis of developmental models suggests specific neural differentiation functions for these molecules. We show that mRNA expression of all seven bHLH family members examined in this study, as well as the divergent homeobox protein Prox1, is present in the adult. Patterns of expression varied considerably between family members, ranging from the limited expression of Mash1 in the neurogenic SGZ of the dentate gyrus to the scattered, widespread profile of Hes5 throughout the dentate gyrus and the hippocampus proper. Moreover, these varied profiles of expression were differentially regulated following status epilepticus, with some increasing (Mash1, Id2), some falling (Hes5, Prox1), and others remaining mostly unchanged (NeuroD/BETA2, NeuroD2/NDRF, Id3, Rath2/Nex1).While the function of these molecules in the adult brain remains to be characterized, our findings support the idea that molecules controlling cell-fate decisions in the developing dentate gyrus are also operative during seizure-induced neurogenesis and plasticity. Using Smart Source Parsing}, Author = {Elliott, R. C. and Khademi, S. and Pleasure, S. J. and Parent, J. M. and Lowenstein, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Neuroscience}, Keywords = {Epilepsy, Temporal Lobe/*genetics/metabolism/physiopathology;Neuropeptides/genetics;DNA-Binding Proteins/genetics;RNA, Messenger/*metabolism;Gene Expression Regulation/*physiology;Rats;Muscarinic Agonists/pharmacology;Neuronal Plasticity/physiology;Helminth Proteins/genetics;Repressor Proteins/genetics;Status Epilepticus/*genetics/metabolism/physiopathology;Animal;Rats, Sprague-Dawley;Nerve Tissue Proteins/genetics;C abstr;Male;Transcription Factors/*genetics;Dentate Gyrus/*metabolism/pathology/physiopathology;Pilocarpine/pharmacology;Annexins/genetics;Homeodomain Proteins/genetics;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Bromodeoxyuridine/pharmacokinetics;Helix-Loop-Helix Motifs/*physiology}, Number = {1}, Organization = {Program in Brain Plasticity and Epilepsy, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.}, Pages = {79-88}, Title = {Differential regulation of basic helix-loop-helix mRNAs in the dentate gyrus following status epilepticus}, Uuid = {6A812D74-81A7-4FC8-80A3-035878E0551A}, Volume = {106}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11564418}} @article{Emerman:2006, Author = {Emerman, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {7505876}, Number = {14}, Organization = {Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109.}, Pages = {5249-50}, Pii = {0601373103}, Pubmed = {16567650}, Title = {How TRIM5\{alpha\}defends against retroviral invasions}, Uuid = {22C64505-DC86-4B54-A851-40AF2FC4D659}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0601373103}} @article{Emery:1987, Abstract = {Cultured mouse spinal neurons were fixed at three different intervals after dendrite amputation: within the first 15 min, at 2 h and at 24 h. Dendrites were amputated at lesion distance of either 50 microns (31\%probability of cell survival) or 100 microns (53\%probability of cell survival) from the edge of their perikarya. When fixed within 15 min, operated neurons showed a two-phase gradient of ultrastructural damage which spread from the transection site towards the perikaryon. At 2 h after dendrite amputation all neurons operated close to their perikarya were categorized as either viable, moribund or dead, based on their appearance with phase contrast microscopy. These categories of response to physical trauma corresponded to distinctly different ultrastructural changes. Moribund neurons were filled with membrane-bound vesicles which were derived from swollen mitochondria and grossly dilated cisternae of the smooth endoplasmic reticulum. The cytoplasm of dead neurons contained large clear areas and many condensed, dark mitochondria. Both moribund and dead neurons lacked cytoskeletal elements. All of these ultrastructural changes are hypothesized to be the result of an increase in the intracellular concentrations of free calcium. Although evidence of residual mitochondrial swelling was present in some surviving neurons at 24 h, the ultrastructure of others was comparable to that of control cells. Some surviving neurons had terminal swellings at the ends of the severed neurites which were very similar to retraction balls of transected axons after CNS trauma.}, Author = {Emery, D. G. and Lucas, J. H. and Gross, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {G;10 Development;Cell Survival;Nerve Degeneration;Animals;Cells, Cultured;Lasers;10 Structural plasticity;11 Glia;Get paper from library;Time Factors;Spinal Cord;Dendrites;Research Support, U.S. Gov't, P.H.S.;Neurons;Mice;Microscopy, Electron;24 Pubmed search results 2008}, Medline = {87304679}, Nlm_Id = {0043312}, Number = {1}, Pages = {41-51}, Pubmed = {3622681}, Title = {The sequence of ultrastructural changes in cultured neurons after dendrite transection}, Uuid = {6E1737C2-EA48-4EB8-BCB9-E4E780E971AD}, Volume = {67}, Year = {1987}} @article{Emsley:2004a, Author = {Emsley, Jason G. and Arlotta, Paola and Macklis, Jeffrey D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Neurons;Glial Fibrillary Acidic Protein;Central Nervous System;17 Transplant Regeneration;Wound Healing;Nerve Regeneration;Astrocytes;11 Glia;review, tutorial;Cells, Cultured;Animals;Vimentin;review}, Month = {5}, Nlm_Id = {7808616}, Number = {5}, Organization = {MGH-HMS Center for Nervous System Repair, Departments of Neurosurgery and Neurology, and Program in Neuroscience, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.}, Pages = {238-40}, Pii = {S0166223604000657}, Pubmed = {15111002}, Title = {Star-cross'd neurons: astroglial effects on neural repair in the adult mammalian CNS}, Uuid = {F93781DE-26A1-4F84-95C2-A3D3FFF0C99C}, Volume = {27}, Year = {2004}, url = {papers/Emsley_TrendsNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2004.02.008}} @article{Englund:2002, Abstract = {Here we examined the ability of human neural progenitors from the embryonic forebrain, expanded for up to a year in culture in the presence of growth factors, to respond to environmental signals provided by the developing rat brain. After survival times of up to more than a year after transplantation into the striatum, the hippocampus, and the subventricular zone, the cells were analyzed using human-specific antisera and the reporter gene green fluorescent protein (GFP). From grafts implanted in the striatum, the cells migrated extensively, especially within white matter structures. Neuronal differentiation was most pronounced at the striatal graft core, with axonal projections extending caudally along the internal capsule into mesencephalon. In the hippocampus, cells migrated throughout the entire hippocampal formation and into adjacent white matter tracts, with differentiation into neurons both in the dentate gyrus and in the CA1-3 regions. Directed migration along the rostral migratory stream to the olfactory bulb and differentiation into granule cells were observed after implantation into the subventricular zone. Glial differentiation occurred at all three graft sites, predominantly at the injection sites, but also among the migrating cells. A lentiviral vector was used to transduce the cells with the GFP gene prior to grafting. The reporter gene was expressed for at least 15 weeks and the distribution of the gene product throughout the entire cytoplasmic compartment of the expressing cells allowed for a detailed morphological analysis of a portion of the grafted cells. The extensive integration and differentiation of in vitro-expanded human neural progenitor cells indicate that multipotent progenitors are capable of responding in a regionally specific manner to cues present in the developing rat brain. 0014-4886 Journal Article}, Author = {Englund, U. and Fricker-Gates, R. A. and Lundberg, C. and Bjorklund, A. and Wictorin, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {Exp Neurol}, Keywords = {Human;Animals;Neuroglia/cytology/metabolism/ultrastructure;Rats;Cell Movement/*physiology;*Fetal Tissue Transplantation;*Stem Cell Transplantation;J pdf;Cell Count;Corpus Striatum/cytology/metabolism;15 Retrovirus mechanism;Lateral Ventricles/cytology/metabolism;*Axons/ultrastructure;Rats, Sprague-Dawley;Cell Differentiation/*physiology;Cell Line;Animals, Newborn;Stem Cells/cytology/metabolism;Support, Non-U.S. Gov't;Prosencephalon/cytology/embryology/transplantation;Hippocampus/cytology/metabolism;Genes, Reporter;Neurons/cytology/metabolism/ultrastructure;Graft Survival;*Brain Tissue Transplantation;Luminescent Proteins/biosynthesis/genetics}, Number = {1}, Organization = {Wallenberg Neuroscience Center, Division of Neurobiology, Lund University, S-221 84 Lund, Sweden.}, Pages = {1-21}, Title = {Transplantation of human neural progenitor cells into the neonatal rat brain: extensive migration and differentiation with long-distance axonal projections}, Uuid = {1F8EB7E3-E335-46E3-81E8-3B971DC928BB}, Volume = {173}, Year = {2002}, url = {papers/Englund_ExpNeurol2002}} @article{Englund:2005, Abstract = {The developing neocortex contains two types of progenitor cells for glutamatergic, pyramidal-projection neurons. The first type, radial glia, produce neurons and glia, divide at the ventricular surface, and express Pax6, a homeodomain transcription factor. The second type, intermediate progenitor cells, are derived from radial glia, produce only neurons, and divide away from the ventricular surface. Here we show that the transition from radial glia to intermediate progenitor cell is associated with upregulation of Tbr2, a T-domain transcription factor, and downregulation of Pax6. Accordingly, Tbr2 expression in progenitor compartments (the subventricular zone and ventricular zone) rises and falls with cortical plate neurogenesis. The subsequent transition from intermediate progenitor cell to postmitotic neuron is marked by downregulation of Tbr2 and upregulation of Tbr1, another T-domain transcription factor. These findings delineate the transcription factor sequence Pax6 -->Tbr2 -->Tbr1 in the differentiation of radial glia -->intermediate progenitor cell -->postmitotic projection neuron. This transcription factor sequence is modified in preplate neurons, in which Tbr2 is transiently coexpressed with Tbr1, and in the direct differentiation pathway from radial glia -->postmitotic projection neuron, in which Tbr2 is expressed briefly or not at all.}, Author = {Englund, Chris and Fink, Andy and Lau, Charmaine and Pham, Diane and Daza, Ray A. M. and Bulfone, Alessandro and Kowalczyk, Tom and Hevner, Robert F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Department of Pathology, University of Washington, Seattle, Washington 98195-7470, USA.}, Pages = {247-51}, Pii = {25/1/247}, Pubmed = {15634788}, Title = {Pax6, Tbr2, and Tbr1 are expressed sequentially by radial glia, intermediate progenitor cells, and postmitotic neurons in developing neocortex}, Uuid = {AF9AEC55-9FB5-4623-A051-4B6958946A99}, Volume = {25}, Year = {2005}, url = {papers/Englund_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2899-04.2005}} @article{Englund:2000, Abstract = {A major obstacle in ex vivo gene transfer has been the loss of transgene expression soon after implantation of the grafted transduced cells. Recently, a lentiviral vector system has been developed which has proven to express high levels of transgenes in vivo after direct injection into the tissue. In this study, we have investigated the use of such a vector for ex vivo gene transfer to the brain. A number of neural cell types were found to be permissive to transduction by the lentiviral vector in vitro and a majority of them expressed the transgene after transplantation to the rat brain. Transgene expression was detected up to 8 weeks post-grafting. These findings suggest that recombinant lentiviral vectors may be used for further development of ex vivo gene therapy protocols to the CNS. 0959-4965 Journal Article}, Author = {Englund, U. and Ericson, C. and Rosenblad, C. and Mandel, R. J. and Trono, D. and Wictorin, K. and Lundberg, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Cell Differentiation;Gene Therapy/trends;Cells, Cultured/cytology/metabolism/transplantation;Genetic Vectors;Green Fluorescent Proteins;Luminescent Proteins;Gene Therapy;Transduction, Genetic;Stem Cells/cytology/metabolism;Animals;*Gene Transfer Techniques;DNA, Recombinant;Brain;Cells, Cultured;Stem Cell Transplantation;Transgenes;Brain Tissue Transplantation;15 Retrovirus mechanism;Genetic Vectors/*genetics;Gene Expression Regulation, Viral/physiology;11 Glia;Luminescent Proteins/genetics;Brain/*virology;Gene Expression Regulation, Viral;DNA, Recombinant/genetics;Gene Transfer Techniques;Rats;Cell Differentiation/genetics;J;Stem Cells;Mice;Lentivirus/*genetics;Research Support, Non-U.S. Gov't;Lentivirus;Humans;Transgenes/*genetics;Human;Support, Non-U.S. Gov't}, Medline = {21033203}, Month = {12}, Nlm_Id = {9100935}, Number = {18}, Organization = {Wallenberg Neuroscience Center, Division of Neurobiology, Lund University, Sweden.}, Pages = {3973-7}, Pubmed = {11192612}, Title = {The use of a recombinant lentiviral vector for ex vivo gene transfer into the rat CNS}, Uuid = {44C3494F-9934-46CD-B342-F65CB34AFC6B}, Volume = {11}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11192612}} @article{Englund:2002a, Abstract = {In vitro expanded neural stemprogenitor cells can undergo region-specific differentiation after transplantation to the developing or adult brain, and display morphologies and markers characteristic of mature neurons. Here we have used patch-clamp techniques to explore whether grafted stem cells also can develop physiological properties of mature neurons and become functionally integrated within host neural circuitry. The immortalized neural progenitor cell line, RN33B, prelabeled with GFP by using a lentiviral vector, was transplanted into the cortex or hippocampus of neonatal rats. We found that the grafted GFP-positive cells differentiated into cells with morphological features of cortical or hippocampal pyramidal neurons, and that many of them had established appropriate cortico-thalamic and contralateral hippocampal connections, respectively, as revealed by retrograde tracing. Whole-cell patch-clamp recordings from grafted cells with morphological characteristics of pyramidal neurons showed that they were able to generate action potentials, and received functional excitatory and inhibitory synaptic inputs from neighboring cells. These data provide evidence that grafted neural progenitors can differentiate into morphologically mature pyramidal projection neurons, establish appropriate long-distance axonal projections, exhibit normal electrophysiological properties, and become functionally integrated into host cortical circuitry.}, Author = {Englund, Ulrica and Bjorklund, Anders and Wictorin, Klas and Lindvall, Olle and Kokaia, Merab}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Stem Cell Transplantation;Synapses;Cell Differentiation;Rats;Action Potentials;Pyramidal Cells;Cell Line;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Hippocampus;22 Stem cells;gamma-Aminobutyric Acid;Receptors, N-Methyl-D-Aspartate;Animals;Cerebral Cortex;Neurons;Axons}, Medline = {22388235}, Month = {12}, Nlm_Id = {7505876}, Number = {26}, Organization = {Sections of Neurobiology and Restorative Neurology, Wallenberg Neuroscience Center, BMC A-11, Lund University, S-221 84 Lund, Sweden Europe.}, Pages = {17089-94}, Pii = {252589099}, Pubmed = {12471158}, Title = {Grafted neural stem cells develop into functional pyramidal neurons and integrate into host cortical circuitry}, Uuid = {4C875399-689E-4696-BF25-AF9CB57ECDBF}, Volume = {99}, Year = {2002}, url = {papers/Englund_ProcNatlAcadSciUSA2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.252589099}} @article{Engstrom:2001, Abstract = {An iron induced model of posttraumatic chronic focal epilepsy in rats was studied with respect to extracellular amino acids, electrophysiology, and morphology, approx. 6 months after intracortical injection of ferrous chloride. Twenty-six of the twenty-eight (93\%) rats developed spontaneous epileptiform EEG-activity and electrical cortical stimulation done in eight animals evoked seizure activity in five animals (62.5\%). Epileptic brain tissue displayed significantly higher extracellular interictal levels of aspartate (ASP), compared to normal brain, measured with intracerebral microdialysis. The interictal levels of serine (SER) were significantly higher at the lesion side compared to the contralateral cortex in epileptic animals. Spontaneous elevations of ASP and glutamate (GLU) levels up to 8 times the basal level were found in 4/5 (80\%). There was no consistent amino acid pattern following the electrically induced seizures, but in association with more intense seizure activity ASP and GLU were elevated. Histopathologically, the necrotic lesions in the cortex contained small vessels and iron pigment loaded astrocytes. Scattered eosinophilic neurons were found in the hippocampus, bilaterally in 37\%of the animals. The results show that a focal epileptiform activity developed in a high percentage of animals that received an intracortical iron injection. The observed amino acid changes in epileptic animals may be involved in the development of seizures in this model of posttraumatic epilepsy.}, Author = {Engstr{\"o}m, E. R. and Hillered, L. and Flink, R. and Kihlstr{\"o}m, L. and Lindquist, C. and Nie, J. X. and Olsson, Y. and Silander, H. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Animals;Craniocerebral Trauma;Serine;Rats;Glutamic Acid;Brain;21 Epilepsy;Aspartic Acid;Epilepsy;Extracellular Space;Rats, Sprague-Dawley;Amino Acids;Male;Microdialysis;Cerebral Cortex;21 Neurophysiology;Ferrous Compounds;24 Pubmed search results 2008;Injections;Electroencephalography;Research Support, Non-U.S. Gov't}, Medline = {21099206}, Month = {2}, Nlm_Id = {8703089}, Number = {2}, Organization = {Department of Neurosurgery, Uppsala University Hospital, S-751-85, Uppsala, Sweden. elisabeth.ronne-engstrom\@nc.uas.lul.se}, Pages = {135-44}, Pii = {S0920121100001911}, Pubmed = {11164702}, Title = {Extracellular amino acid levels measured with intracerebral microdialysis in the model of posttraumatic epilepsy induced by intracortical iron injection}, Uuid = {53BACC36-5EB3-430D-BFE8-91E0CE3C5DBD}, Volume = {43}, Year = {2001}} @article{Ennis:2001, Abstract = {Olfactory receptor neurons of the nasal epithelium project via the olfactory nerve (ON) to the glomeruli of the main olfactory bulb, where they form glutamatergic synapses with the apical dendrites of mitral and tufted cells, the output cells of the olfactory bulb, and with juxtaglomerular interneurons. The glomerular layer contains one of the largest population of dopamine (DA) neurons in the brain, and DA in the olfactory bulb is found exclusively in juxtaglomerular neurons. D2 receptors, the predominant DA receptor subtype in the olfactory bulb, are found in the ON and glomerular layers, and are present on ON terminals. In the present study, field potential and single-unit recordings, as well as whole cell patch-clamp techniques, were used to investigate the role of DA and D2 receptors in glomerular synaptic processing in rat and mouse olfactory bulb slices. DA and D2 receptor agonists reduced ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells. Spontaneous and ON-evoked spiking of mitral cells was also reduced by DA and D2 agonists, and enhanced by D2 antagonists. DA did not produce measurable postsynaptic changes in juxtaglomerular cells, nor did it alter their responses to mitral/tufted cell inputs. DA also reduced 1) paired-pulse depression of ON-evoked synaptic responses in mitral/tufted and juxtaglomerular cells and 2) the amplitude and frequency of spontaneous, but not miniature, excitatory postsynaptic currents in juxtaglomerular cells. Taken together, these findings are consistent with the hypothesis that activation of D2 receptors presynaptically inhibits ON terminals. DA and D2 agonists had no effect in D2 receptor knockout mice, suggesting that D2 receptors are the only type of DA receptors that affect signal transmission from the ON to the rodent olfactory bulb.}, Author = {Ennis, M. and Zhou, F. M. and Ciombor, K. J. and Aroniadou-Anderjaska, V. and Hayar, A. and Borrelli, E. and Zimmer, L. A. and Margolis, F. and Shipley, M. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {J Neurophysiol}, Keywords = {Olfactory Nerve/*physiology;Olfactory Receptor Neurons/*physiology;Receptors, Presynaptic/*physiology;Olfactory Bulb/cytology/physiology;In Vitro;Electrophysiology;Rats;13 Olfactory bulb anatomy;Patch-Clamp Techniques;Animal;Excitatory Postsynaptic Potentials/physiology;Mice, Inbred C57BL;Male;Support, Non-U.S. Gov't;Extracellular Space/physiology;Receptors, Dopamine D2/genetics/*physiology;Synaptic Transmission/physiology;Mice, Knockout;Support, U.S. Gov't, P.H.S.;Nerve Endings/*physiology;I pdf;Mice}, Number = {6}, Organization = {Department of Anatomy and Neurobiology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. mennis\@umaryland.edu}, Pages = {2986-97.}, Title = {Dopamine D2 receptor-mediated presynaptic inhibition of olfactory nerve terminals}, Uuid = {2D82F0DC-8D85-4D0B-ADEF-955A80999859}, Volume = {86}, Year = {2001}, url = {papers/Ennis_JNeurophysiol2001}} @article{Epperly:2003, Abstract = {There is a rapid onset of organizing alveolitis/fibrosis at 120-140 d after whole lung irradiation of C57BL/6J mice. To test the hypothesis that circulating cells of bone marrow origin contribute to irradiation fibrosis, irradiated chimeric green fluorescent protein (GFP)+ C57BL/6J mice were followed for GFP+ cells in areas of lung fibrosis. In a second experimental model, C57BL/6J female mice received 20 Gy total lung irradiation, and after 60 or 80 d were intravenously injected with cells from a clonal GFP+ male bone marrow stromal cell line or male GFP+ whole bone marrow, respectively. The mice were then followed for the development of pulmonary fibrosis, and the contribution of Y-probe-positive, GFP+ cells to fibrotic areas was quantitated. Bromodeoxyuridine labeling of developing fibrotic areas showed that the cell division occurred predominantly in GFP+, Y-probe-positive, and vimentin-positive cells. Immunohistochemistry demonstrated that these cells were macrophages and fibroblasts, not endothelial cells. Mice that received manganese superoxide dismutase-plasmid/liposome intratracheal injection 24 h before total lung irradiation demonstrated a decrease in GFP+ fibroblastic cells in the lung. Thus, pulmonary irradiation fibrosis contains proliferating cells of bone marrow origin, and gene therapy prevention of this condition acts in part by decreasing the migration and proliferation of marrow origin cells.}, Author = {Epperly, Michael W. and Guo, Hongliang and Gretton, Joan E. and Greenberger, Joel S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1044-1549}, Journal = {Am J Respir Cell Mol Biol}, Keywords = {Animals;Macrophages;Fibroblasts;Myocardium;Female;Superoxide Dismutase;Mice, Transgenic;Fibrosis;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Male;Time Factors;Microscopy, Fluorescence;Cell Line;Pulmonary Fibrosis;Research Support, U.S. Gov't, P.H.S.;Bone Marrow Cells;Bone Marrow;In Situ Hybridization;Mice;Cell Division;Y Chromosome;Luminescent Proteins;Immunohistochemistry;Bromodeoxyuridine;Lung}, Medline = {22760085}, Month = {8}, Nlm_Id = {8917225}, Number = {2}, Organization = {Department of Radiation Oncology, University of Pittsburgh Cancer Institute, PA, USA.}, Pages = {213-24}, Pii = {2002-0069OC}, Pubmed = {12649121}, Title = {Bone marrow origin of myofibroblasts in irradiation pulmonary fibrosis}, Uuid = {429B97FE-3653-459C-9393-3E96AA740D4C}, Volume = {29}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1165/rcmb.2002-0069OC}} @article{Epsztein:2005, Abstract = {Glutamatergic mossy fibers of the hippocampus sprout in temporal lobe epilepsy and establish aberrant synapses on granule cells from which they originate. There is currently no evidence for the activation of kainate receptors (KARs) at recurrent mossy fiber synapses in epileptic animals, despite their important role at control mossy fiber synapses. We report that KARs are involved in ongoing glutamatergic transmission in granule cells from chronic epileptic but not control animals. KARs provide a substantial component of glutamatergic activity, because they support half of the non-NMDA receptor-mediated excitatory drive in these cells. KAR-mediated EPSC(KA)s are selectively generated by recurrent mossy fiber inputs and have a slower kinetics than EPSC(AMPA). Therefore, in addition to axonal rewiring, sprouting of mossy fibers induces a shift in the nature of glutamatergic transmission in granule cells that may contribute to the physiopathology of the dentate gyrus in epileptic animals.}, Author = {Epsztein, J{\'e}r\^{o}me and Represa, Alfonso and Jorquera, Isabel and Ben-Ari, Yehezkel and Cr{\'e}pel, Val{\'e}rie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Electric Stimulation;Animals;Synapses;In Vitro;Rats;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;21 Epilepsy;Patch-Clamp Techniques;Epilepsy;Hippocampus;Rats, Wistar;Disease Models, Animal;Male;Status Epilepticus;Quinoxalines;Mossy Fibers, Hippocampal;21 Neurophysiology;Receptors, Kainic Acid;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Month = {9}, Nlm_Id = {8102140}, Number = {36}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, Unit{\'e} 29, Universit{\'e} de la M{\'e}diterran{\'e}e, Parc Scientifique de Luminy, 13273 Marseille Cedex 09, France.}, Pages = {8229-39}, Pii = {25/36/8229}, Pubmed = {16148230}, Title = {Recurrent mossy fibers establish aberrant kainate receptor-operated synapses on granule cells from epileptic rats}, Uuid = {27654F2A-379C-41D1-8D91-AF84C558D3FE}, Volume = {25}, Year = {2005}, url = {papers/Epsztein_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1469-05.2005}} @article{Epsztein:2006, Abstract = {Ischemic strokes are often associated with late-onset epilepsy, but the underlying mechanisms are poorly understood. In the hippocampus, which is one of the regions most sensitive to ischemic challenge, global ischemia induces a complete loss of CA1 pyramidal neurons, whereas the resistant CA3 pyramidal neurons display a long-term hyperexcitability several months after the insult. The mechanisms of this long-term hyperexcitability remain unknown despite its clinical implication. Using chronic in vivo EEG recordings and in vitro field recordings in slices, we now report spontaneous interictal epileptiform discharges in the CA3 area of the hippocampus from post-ischemic rats several months after the insult. Whole-cell recordings from CA3 pyramidal neurons, revealed a permanent reduction in the frequency of spontaneous and miniature GABAergic IPSCs and a parallel increase in the frequency of spontaneous and miniature glutamatergic postsynaptic currents. Global ischemia also induced a dramatic loss of GABAergic interneurons and terminals together with an increase in glutamatergic terminals in the CA3 area of the hippocampus. Altogether, our results show a morpho-functional reorganization in the CA3 network several months after global ischemia, resulting in a net shift in the excitatory-inhibitory balance toward excitation that may constitute a substrate for the generation of epileptiform discharges in the post-ischemic hippocampus.}, Author = {Epsztein, J{\'e}r\^{o}me and Milh, Mathieu and Bihi, Rachid Id and Jorquera, Isabel and Ben-Ari, Yehezkel and Represa, Alfonso and Cr{\'e}pel, Val{\'e}rie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {gamma-Aminobutyric Acid;Electrophysiology;Animals;Synapses;Nerve Endings;Rats;In Vitro;Glutamic Acid;Synaptic Transmission;Patch-Clamp Techniques;21 Epilepsy;Epilepsy;Hippocampus;Pyramidal Cells;Rats, Wistar;Male;21 Neurophysiology;Reperfusion Injury;Interneurons;24 Pubmed search results 2008;Neural Inhibition;Electroencephalography;Research Support, Non-U.S. Gov't}, Month = {6}, Nlm_Id = {8102140}, Number = {26}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e, and Universit{\'e} de La M{\'e}diterran{\'e}e, Parc scientifique de Luminy, 13273 Marseille Cedex 09, France.}, Pages = {7082-92}, Pii = {26/26/7082}, Pubmed = {16807337}, Title = {Ongoing epileptiform activity in the post-ischemic hippocampus is associated with a permanent shift of the excitatory-inhibitory synaptic balance in CA3 pyramidal neurons}, Uuid = {A102FC91-4D10-4CA5-B26E-03E2EE9FE548}, Volume = {26}, Year = {2006}, url = {papers/Epsztein_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1666-06.2006}} @article{Erchova:2002, Abstract = {Experiments were carried out to learn about changes in sensory cortical processing associated with different levels of anaesthesia. Traditionally this question has been addressed by studying single neurons. Because state changes are likely to influence the relationships between neurons, the present experiments were undertaken to investigate the spatial and temporal firing patterns distributed across cortex. Using 5 x 5 or 10 x 10 microelectrode arrays, spontaneous and stimulus-evoked activity of multineuron clusters was recorded from rat somatosensory 'barrel' cortex (the whisker representation) during a light surgical stage of urethane anaesthesia, and after two supplemental doses of urethane which led to intermediate and deep levels of anaesthesia. At all depths of anaesthesia, spontaneously occurring action potentials at a single electrode tended to be clustered into 'bursts.' With increasing anaesthetic depth, bursts became more prominent and rhythmic, and increasingly synchronized between cortical barrel-columns. Burst frequency decreased and fewer spikes occurred outside bursts, leading to a decrease in the overall spontaneous firing rate. The cortical territory engaged by individual whiskers contracted with increasing depth of anaesthesia, leading to the spatial segregation of whisker representations. At all stages of anaesthesia, whisker stimulation produced the maximal cortical response when delivered close to burst onset. These observations show that ongoing spontaneous activity modulates sensory response properties and makes peripheral tactile information accessible to a cortical territory whose size is determined by the phase of burst cycle. The possible significance of the cyclic cortical responsiveness encountered during urethane anaesthesia to cortical processing in awake rats is considered.}, Author = {Erchova, Irina A. and Lebedev, Mikhail A. and Diamond, Mathew E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Anesthetics;Dose-Response Relationship, Drug;Animals;Touch;Rats;Neuronal Plasticity;Cortical Synchronization;Afferent Pathways;Synaptic Transmission;Periodicity;Vibrissae;Rats, Wistar;Biological Clocks;Male;Nerve Net;Action Potentials;Neurons;21 Neurophysiology;Somatosensory Cortex;21 Cortical oscillations;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8918110}, Number = {4}, Organization = {Cognitive Neuroscience Sector, International School for Advanced Studies, Via Beirut, 9, 34014 Trieste, Italy.}, Pages = {744-52}, Pubmed = {11886439}, Title = {Somatosensory cortical neuronal population activity across states of anaesthesia}, Uuid = {3E0963E9-16B4-4442-A329-24D0F9C882CE}, Volume = {15}, Year = {2002}} @article{Erdi:1997, Abstract = {Dynamics of single cells, small networks and large cell populations are the subject of investigation. The generation and propagation of action potentials in the two major cell types of the olfactory bulb, i.e. in the mitral and granule cells, are simulated by multi-compartmental modeling techniques. The specific effects of the individual ionic currents, the propagation of the signals through the compartments, and dynamic phenomena occurring in small networks (such as synchronized oscillation due to excitatory and inhibitory coupling) have been demonstrated. A statistical model is given to describe the electrical activity patterns of large neural populations. The model is applied for describing the CA3 region of the hippocampus by incorporating some basic electrophysiological properties of hippocampal pyramidal and inhibitory neurons. Population activities as well as underlying single cell voltages are simulated during population bursts in the model of disinhibited hippocampal CA3 slice. Using Smart Source Parsing}, Author = {Erdi, P. and Aradi, I. and Grobler, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Biosystems}, Keywords = {Models, Biological;Olfactory Bulb/*cytology/physiology;02 Adult neurogenesis migration;Neurons/*physiology;03 Adult neurogenesis progenitor source;Hippocampus/*cytology/physiology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Periodicity;BB abstr}, Number = {1-2}, Organization = {Department of Biophysics, KFKI Research Institute for Particle and Nuclear Physics of the Hungarian Academy of Sciences, Budapest. erdi\@rmki.kfki.hu}, Pages = {45-53}, Title = {Rhythmogenesis in single cells and population models: olfactory bulb and hippocampus}, Uuid = {47626208-ABAD-4EF6-B6D1-EF5F04093635}, Volume = {40}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8971195}} @article{Eriksson:1998, Abstract = {The genesis of new cells, including neurons, in the adult human brain has not yet been demonstrated. This study was undertaken to investigate whether neurogenesis occurs in the adult human brain, in regions previously identified as neurogenic in adult rodents and monkeys. Human brain tissue was obtained postmortem from patients who had been treated with the thymidine analog, bromodeoxyuridine (BrdU), that labels DNA during the S phase. Using immunofluorescent labeling for BrdU and for one of the neuronal markers, NeuN, calbindin or neuron specific enolase (NSE), we demonstrate that new neurons, as defined by these markers, are generated from dividing progenitor cells in the dentate gyrus of adult humans. Our results further indicate that the human hippocampus retains its ability to generate neurons throughout life.}, Author = {Eriksson, P. S. and Perfilieva, E. and Bjork-Eriksson, T. and Alborn, A. M. and Nordborg, C. and Peterson, D. A. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {Nat Med}, Keywords = {Rodentia;Human;Neurons/cytology/pathology/*physiology;Stem Cells/cytology/pathology/physiology;Dentate Gyrus/cytology/pathology/*physiology;Animal;Glial Fibrillary Acidic Protein/analysis;Nerve Tissue Proteins/analysis;01 Adult neurogenesis general;DNA/biosynthesis;Calcium-Binding Protein, Vitamin D-Dependent/analysis;Haplorhini;Support, Non-U.S. Gov't;Hippocampus/cytology/pathology/*physiology;Adult;Support, U.S. Gov't, P.H.S.;*Nerve Regeneration;Phosphopyruvate Hydratase/analysis;Bromodeoxyuridine;Biological Markers/analysis;A-10;Astrocytes/cytology/pathology/physiology}, Number = {11}, Organization = {Department of Clinical Neuroscience, Institute of Neurology, Sahlgrenska University Hospital, Goteborg, Sweden.}, Pages = {1313-7.}, Title = {Neurogenesis in the adult human hippocampus}, Uuid = {62B56769-CCDD-11D9-8C77-000D9346EC2A}, Volume = {4}, Year = {1998}, url = {papers/Eriksson_NatMed1998.pdf}} @article{Espinosa-Heidmann:2003, Abstract = {PURPOSE: The pathogenesis of choroidal neovascularization (CNV) is postulated to be driven by angiogenesis, a process in which the cellular components of the new vessel complex are derived from cells resident within an adjacent preexisting capillary. Recently, an alternative paradigm, termed postnatal vasculogenesis, has been shown to contribute to some forms of neovascularization. In vasculogenesis, the cellular components of the new vessel complex are derived from circulating vascular progenitors from bone marrow. In the current study, transplantation of green fluorescent protein (GFP)-labeled bone marrow and laser-induced CNV were combined to examine the contribution of vasculogenesis to the formation of CNV. METHODS: Ten adult C57BL/6 female mice were used as recipients for bone marrow transplantation. Bone marrow was obtained from three C57BL/6 female mice transgenic for the beta-actin promoter GFP. One month after bone marrow transplantation, CNV was induced in recipient mice by making four separate burns in the choroid of each eye with a red diode laser. Four weeks after CNV was induced, eyes of recipient mice were processed for immunohistochemistry to detect GFP and markers for vascular smooth muscle cells (alpha-smooth muscle actin, desmin, and NG2 chondroitin sulfate proteoglycan), endothelial cells (CD31, BS-1 lectin), or macrophages (F4/80). RESULTS: GFP-labeled cells represented 17\%of the total cell population in the lesion. Many of the GFP-labeled cells were immunoreactive for alpha-smooth muscle actin (39\%), desmin, NG2, CD31 (41\%), BS-1 lectin, or F4/80. GFP-labeled cells were morphologically indistinguishable from cells normally present in CNV lesions. CONCLUSIONS: This study is the first to demonstrate that bone marrow-derived progenitor cells are a source of endothelial and smooth musclelike cells in CNV.}, Author = {Espinosa-Heidmann, Diego G. and Caicedo, Alejandro and Hernandez, Eleut P. and Csaky, Karl G. and Cousins, Scott W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0146-0404}, Journal = {Invest Ophthalmol Vis Sci}, Keywords = {Hematopoietic Stem Cells;Fluorescent Antibody Technique, Indirect;Animals;Proteoglycans;Antigens, Differentiation;Female;Indicators and Reagents;Choroidal Neovascularization;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Antigens, CD31;Hematopoietic Stem Cell Transplantation;Research Support, U.S. Gov't, P.H.S.;Antigens;Choroid;Mice;Muscle, Smooth, Vascular;Actins;Luminescent Proteins;Biological Markers;Laser Coagulation;Desmin;Endothelium, Vascular}, Medline = {22939978}, Month = {11}, Nlm_Id = {7703701}, Number = {11}, Organization = {Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, Florida 33136, USA.}, Pages = {4914-9}, Pubmed = {14578417}, Title = {Bone marrow-derived progenitor cells contribute to experimental choroidal neovascularization}, Uuid = {3A53E54E-4F42-4719-833B-516285066994}, Volume = {44}, Year = {2003}} @article{Estivill-Torrus:2002, Abstract = {In the proliferative zone of the developing cerebral cortex, multipotential progenitors predominate early in development and divide to increase the progenitor pool. As corticogenesis progresses, proportionately fewer progenitors are produced and, instead, cell divisions yield higher numbers of postmitotic neurones or glial cells. As the switch from the generation of progenitors to that of differentiated cells occurs, the orientation of cell division alters from predominantly symmetrical to predominantly asymmetrical. It has been hypothesised that symmetrical divisions expand the progenitor pool, whereas asymmetrical divisions generate postmitotic cells, although this remains to be proved. The molecular mechanisms regulating these processes are poorly understood. The transcription factor Pax6 is highly expressed in the cortical proliferative zone and there are morphological defects in the Pax6(Sey/Sey) (Pax6 null) cortex, but little is known about the principal cellular functions of Pax6 in this region. We have analysed the cell-cycle kinetics, the progenitor cleavage orientation and the onset of expression of differentiation markers in Pax6(Sey/Sey) cortical cells in vivo and in vitro. We showed that, early in corticogenesis at embryonic day (E) 12.5, the absence of Pax6 accelerated cortical development in vivo, shortening the cell cycle and the time taken for the onset of expression of neural-specific markers. This also occurred in dissociated culture of isolated cortical cells, indicating that the changes were intrinsic to the cortical cells. From E12.5 to E15.5, proportions of asymmetrical divisions increased more rapidly in mutant than in wild-type embryos. By E15.5, interkinetic nuclear migration during the cell cycle was disrupted and the length of the cell cycle was significantly longer than normal in the Pax6(Sey/Sey) cortex, with a lengthening of S phase. Together, these results show that Pax6 is required in developing cortical progenitors to control the cell-cycle duration, the rate of progression from symmetrical to asymmetrical division and the onset of expression of neural-specific markers. 0950-1991 Journal Article}, Author = {Estivill-Torrus, G. and Pearson, H. and van Heyningen, V. and Price, D. J. and Rashbass, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Development}, Keywords = {Pregnancy;10 Development;Animals;Stem Cells/cytology/*physiology;Cells, Cultured;Cell Cycle/physiology;Female;Homeodomain Proteins/*metabolism;Mice, Transgenic;Cerebral Cortex/cytology/*embryology/growth &development;Cell Differentiation/*physiology;Support, Non-U.S. Gov't;Neuroglia/physiology;Cell Division/*physiology;Transcription Factors/*metabolism;Cell Size;Nerve Tissue Proteins/metabolism;Mice;Immunohistochemistry;Biological Markers;Neurons/physiology;F}, Number = {2}, Organization = {Department of Biomedical Sciences, University of Edinburgh Medical School, Hugh Robson Building, George Square, Edinburgh EH8 9XD, UK.}, Pages = {455-66}, Pubmed = {11807037}, Title = {Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors}, Uuid = {141767D5-B5F4-4825-B349-FED10063DB1B}, Volume = {129}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11807037}} @article{Estivill-Torrus:2007, Abstract = {Lysophosphatidic acid (LPA) is a simple phospholipid with extracellular signaling properties mediated by specific G protein-coupled receptors. At least 2 LPA receptors, LPA(1) and LPA(2), are expressed in the developing brain, the former enriched in the neurogenic ventricular zone (VZ), suggesting a normal role in neurogenesis. Despite numerous studies reporting the effects of exogenous LPA using in vitro neural models, the first LPA(1) loss-of-function mutants reported did not show gross cerebral cortical defects in the 50\%that survived perinatal demise. Here, we report a role for LPA(1) in cortical neural precursors resulting from analysis of a variant of a previously characterized LPA(1)-null mutant that arose spontaneously during colony expansion. These LPA(1)-null mice, termed maLPA(1), exhibit almost complete perinatal viability and show a reduced VZ, altered neuronal markers, and increased cortical cell death that results in a loss of cortical layer cellularity in adults. These data support LPA(1) function in normal cortical development and suggest that the presence of genetic modifiers of LPA(1) influences cerebral cortical development.}, Author = {Estivill-Torr{\'u}s, and Llebrez-Zayas, and Matas-Rico, and Sant{\'\i}n, and Pedraza, and De Diego, and Del Arco, and Fern{\'a}ndez-Llebrez, and Chun, and De Fonseca,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {9110718}, Organization = {Unidad de Investigaci{\'o}n, Fundaci{\'o}n IMABIS, Hospital Carlos Haya, E-29010 M{\'a}laga, Spain.}, Pii = {bhm132}, Pubmed = {17656621}, Title = {Absence of LPA1 Signaling Results in Defective Cortical Development}, Uuid = {F1577208-B96D-4828-A0D0-D894819E6DFF}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhm132}} @article{Eugenin:2006, Abstract = {Encephalitis and dementia associated with acquired immunodeficiency syndrome (AIDS) are characterized by leukocyte infiltration into the CNS, microglia activation, aberrant chemokine expression, blood-brain barrier (BBB) disruption, and eventual loss of neurons. Little is known about whether human immunodeficiency virus 1 (HIV-1) infection of leukocytes affects their ability to transmigrate in response to chemokines and to alter BBB integrity. We now demonstrate that HIV infection of human leukocytes results in their increased transmigration across our tissue culture model of the human BBB in response to the chemokine CCL2, as well as in disruption of the BBB, as evidenced by enhanced permeability, reduction of tight junction proteins, and expression of matrix metalloproteinases (MMP)-2 and MMP-9. HIV-infected cells added to our model did not transmigrate in the absence of CCL2, nor did this condition alter BBB integrity. The chemokines CXCL10/interferon-gamma-inducible protein of 10 kDa, CCL3/macrophage inflammatory protein-1alpha, or CCL5/RANTES (regulated on activation normal T-cell expressed and secreted) did not enhance HIV-infected leukocyte transmigration or BBB permeability. The increased capacity of HIV-infected leukocytes to transmigrate in response to CCL2 correlated with their increased expression of CCR2, the chemokine receptor for CCL2. These data suggest that CCL2, but not other chemokines, plays a key role in infiltration of HIV-infected leukocytes into the CNS and the subsequent pathology characteristic of NeuroAIDS.}, Author = {Eugenin, Eliseo A. and Osiecki, Kristin and Lopez, Lillie and Goldstein, Harris and Calderon, Tina M. and Berman, Joan W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {8102140}, Number = {4}, Organization = {Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.}, Pages = {1098-106}, Pii = {26/4/1098}, Pubmed = {16436595}, Title = {CCL2/monocyte chemoattractant protein-1 mediates enhanced transmigration of human immunodeficiency virus (HIV)-infected leukocytes across the blood-brain barrier: a potential mechanism of HIV-CNS invasion and NeuroAIDS}, Uuid = {4C30E377-CB8B-4604-9218-9A7C4EDEA585}, Volume = {26}, Year = {2006}, url = {papers/Eugenin_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3863-05.2006}} @article{Ever:2005, Abstract = {Cells with radial morphology in the developing brain were first identified more than 100 years ago. These cells, later termed radial glia, have been studied primarily as migratory scaffolds and glial progenitors. However, it has become increasingly clear, on the basis of in vitro studies and more recent in vivo fate mapping experiments, that radial glia also generate neurons during embryonic development. Now the challenge will be to understand the signaling events that regulate the spatial and temporal heterogeneity of these cells and their developmental potential. Recent work has identified the Notch, ErbB, and fibroblast growth factor signaling pathways as central to the regulation of radial 'glial' progenitors.}, Author = {Ever, Leah and Gaiano, Nicholas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, Pages = {29-33}, Pii = {S0959-4388(05)00006-1}, Pubmed = {15721741}, Title = {Radial 'glial' progenitors: neurogenesis and signaling}, Uuid = {2E7D982F-150A-488F-921E-FDB861E3C4C6}, Volume = {15}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.01.005}} @article{Everhart:2005, Abstract = {To facilitate study of alveolar macrophages in vivo, we developed a method to rapidly and efficiently replace resident alveolar macrophages with macrophages of a different (donor) genotype. Chimeric mice were generated by lethal irradiation followed by fetal liver transplantation (FLT) using green fluorescent protein (GFP) transgenic reporter mice as donors. Kinetics of peripheral blood monocyte (PBM) and alveolar macrophage reconstitution was determined 4 and 10 weeks post-FLT by quantifying the percentage of GFP+ cells. To enhance the recruitment of donor monocytes into the lung after FLT, mice were treated with intratracheal administration of liposomal clodronate to deplete host alveolar macrophages at 6 weeks post-FLT. PBM reconstitution occurred by 4 weeks after FLT (85.7+/-1.6\%of CD11b+/Gr-1+ monocytes were GFP+), and minimal alveolar macrophage repopulation was observed (9.5\%GFP+). By 10 weeks following FLT, 48\%of alveolar macrophages were GFP+ by immunostaining of macrophages on lung tissue sections, and 55.1 +/- 1.6\%of lung lavage macrophages were GFP+ by fluorescein-activated cell sorter analysis. Clodronate treatment resulted in a significant increase in GFP+ alveolar macrophages 10 weeks after FLT. By immunostaining, 90\%of macrophages were GFP+ on lung tissue sections and 87.5 +/- 1.1\%GFP+ in lung lavage (compared with GFP-transgenic controls). The ability of newly recruited alveolar macrophages to clear Pseudomonas aeruginosa and activate nuclear factor-kappaB in response to Eschericia coli lipopolysaccharide demonstrated normal macrophage function. Optimizing this methodology provides an important tool for the study of specific genes and their contribution to alveolar macrophage function in vivo.}, Author = {Everhart, M. Brett and Han, Wei and Parman, Kelly S. and Polosukhin, Vasiliy V. and Zeng, Heng and Sadikot, Ruxana T. and Li, Bo and Yull, Fiona E. and Christman, John W. and Blackwell, Timothy S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0741-5400}, Journal = {J Leukoc Biol}, Keywords = {11 Glia}, Month = {2}, Nlm_Id = {8405628}, Number = {2}, Organization = {Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2650, USA.}, Pages = {173-80}, Pii = {jlb.1203647}, Pubmed = {15563581}, Title = {Intratracheal administration of liposomal clodronate accelerates alveolar macrophage reconstitution following fetal liver transplantation}, Uuid = {380CDFE2-6F4E-4389-991D-39256CE322C6}, Volume = {77}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1189/jlb.1203647}} @article{Ewald:2008, Abstract = {NMDA receptors (NMDARs) are important for neuronal development and circuit formation. The NMDAR subunits NR2A and NR2B are biophysically distinct and differentially expressed during development but their individual contribution to structural plasticity is unknown. Here we test whether NR2A and NR2B subunits have specific functions in the morphological development of tectal neurons in living Xenopus tadpoles. We use exogenous subunit expression and endogenous subunit knockdown to shift synaptic NMDAR composition toward NR2A or NR2B, as shown electrophysiologically. We analyzed the dendritic arbor structure and found evidence for both overlapping and distinct functions of NR2A and NR2B in dendritic development. Control neurons develop regions of high local branch density in their dendritic arbor, which may be important for processing topographically organized inputs. Exogenous expression of either NR2A or NR2B decreases local branch clusters, indicating a requirement for both subunits in dendritic arbor development. Knockdown of endogenous NR2A reduces local branch clusters, whereas knockdown of NR2B has no effect on branch clustering. Analysis of the underlying branch dynamics shows that exogenous NR2B-expressing neurons are more dynamic than control or exogenous NR2A-expressing neurons, demonstrating subunit-specific regulation of branch dynamics. Visual experience-dependent increases in dendritic arbor growth rate seen in control neurons are blocked in both exogenous NR2A- and NR2B-expressing neurons. These experiments indicate that NR2A and NR2B have subunit-specific properties in dendritic arbor development, but also overlapping functions, indicating a requirement for both subunits in neuronal development.}, Author = {Ewald, Rebecca C. and Van Keuren-Jensen, Kendall R. and Aizenman, Carlos D. and Cline, Hollis T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;research support, non-u.s. gov't;Dendrites;Excitatory Postsynaptic Potentials;Rats;Neuronal Plasticity;10 circuit formation;comparative study;research support, n.i.h., extramural;Animals;Receptors, N-Methyl-D-Aspartate;Xenopus laevis;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8102140}, Number = {4}, Organization = {Watson School of Biological Sciences and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.}, Pages = {850-61}, Pii = {28/4/850}, Pubmed = {18216193}, Title = {Roles of NR2A and NR2B in the development of dendritic arbor morphology in vivo}, Uuid = {370B0E5F-05A0-4074-914B-E5D5325C3E2B}, Volume = {28}, Year = {2008}, url = {papers/Ewald_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5078-07.2008}} @article{Eytan:2006, Abstract = {Cognitive processes depend on synchronization and propagation of electrical activity within and between neuronal assemblies. In vivo measurements show that the size of individual assemblies depends on their function and varies considerably, but the timescale of assembly activation is in the range of 0.1-0.2 s and is primarily independent of assembly size. Here we use an in vitro experimental model of cortical assemblies to characterize the process underlying the timescale of synchronization, its relationship to the effective topology of connectivity within an assembly, and its impact on propagation of activity within and between assemblies. We show that the basic mode of assembly activation, "network spike," is a threshold-governed, synchronized population event of 0.1-0.2 s duration and follows the logistics of neuronal recruitment in an effectively scale-free connected network. Accordingly, the sequence of neuronal activation within a network spike is nonrandom and hierarchical; a small subset of neurons is consistently recruited tens of milliseconds before others. Theory predicts that scale-free topology allows for synchronization time that does not increase markedly with network size; our experiments with networks of different densities support this prediction. The activity of early-to-fire neurons reliably forecasts an upcoming network spike and provides means for expedited propagation between assemblies. We demonstrate this capacity by observing the dynamics of two artificially coupled assemblies in vitro, using neuronal activity of one as a trigger for electrical stimulation of the other.}, Author = {Eytan, Danny and Marom, Shimon}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Nerve Net;Neurons;21 Cortical oscillations;24 Pubmed search results 2008;21 Neurophysiology;Recruitment, Neurophysiological;Action Potentials;research support, non-u.s. gov't ;Rats;Time Factors;Biophysics;Cortical Synchronization;Animals;Cells, Cultured;Cerebral Cortex;Differential Threshold;Microelectrodes}, Month = {8}, Nlm_Id = {8102140}, Number = {33}, Organization = {Department of Physiology and Biophysics, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 32000, Israel.}, Pages = {8465-76}, Pii = {26/33/8465}, Pubmed = {16914671}, Title = {Dynamics and effective topology underlying synchronization in networks of cortical neurons}, Uuid = {DB4DF5EA-9602-49CD-A8BB-8EBCCBB9F7ED}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1627-06.2006}} @article{Eyupoglu:2003, Abstract = {Primary neuronal destruction in the central nervous system triggers rapid changes in glial morphology and function, after which activated glial cells contribute to secondary neuronal changes. Here we show that, after entorhinal cortex lesion, activation of microglia, but not other glial cells, leads to massive secondary dendritic changes of deafferentiated hippocampal neurons. Blocking of microglial activation in vivo reduced this secondary neuronal damage and enhanced regenerative axonal sprouting. In contrast, abolishing astrocytes or oligodendroglia did not result in specific neuronal changes. Furthermore, primary damage leads to an interleukin 1beta up-regulation, which is attenuated by the immuno-modulator transforming growth factor beta1, whereas tumor necrosis factor alpha is not affected. Modification of microglial activity following denervation of the hippocampus protects neurons from secondary dendritic alterations and therefore enables their reinnervation. These data render activated microglia a putative therapeutic target during the course of axonal degeneration.}, Author = {Ey{\"u}poglu, Ilker Y. and Bechmann, Ingo and Nitsch, Robert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {Dendrites;Cytokines;Rats;Hippocampus;Nerve Regeneration;Anti-Inflammatory Agents;Denervation;Cell Survival;11 Glia;Microglia;Transforming Growth Factor beta;Animals;Neurons;Axons}, Medline = {22658121}, Month = {6}, Nlm_Id = {8804484}, Number = {9}, Organization = {Institute of Anatomy, Department of Cell and Neurobiology, Humboldt University Hospital (Charit{\'e}), 10098 Berlin, Germany. robert.nitsch\@charite.de}, Pages = {1110-1}, Pii = {02-0825fje}, Pubmed = {12692086}, Title = {Modification of microglia function protects from lesion-induced neuronal alterations and promotes sprouting in the hippocampus}, Uuid = {D91C5624-C402-4F66-AFB3-079CE93905EE}, Volume = {17}, Year = {2003}, url = {papers/Eyüpoglu_FASEBJ2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.02-0825fje}} @article{Fabel:2003, Abstract = {Declining learning and memory function is associated with the attenuation of adult hippocampal neurogenesis. As in humans, chronic stress or depression in animals is accompanied by hippocampal dysfunction, and neurogenesis is correspondingly down regulated, in part, by the activity of the hypothalamic-pituitary-adrenal axis as well as glutamatergic and serotonergic networks. Antidepressants can reverse this effect over time but one of the most clinically effective moderators of stress or depression and robust stimulators of neurogenesis is simple voluntary physical exercise such as running. Curiously, running also elevates circulating stress hormone levels yet neurogenesis is doubled in running animals. In evaluating the signalling that running provides to the central nervous system in mice, we have found that peripheral vascular endothelial growth factor (VEGF) is necessary for the effects of running on adult hippocampal neurogenesis. Peripheral blockade of VEGF abolished running-induced neurogenesis but had no detectable effect on baseline neurogenesis in non-running animals. These data suggest that VEGF is an important element of a 'somatic regulator'of adult neurogenesis and that these somatic signalling networks can function independently of the central regulatory networks that are typically considered in the context of hippocampal neurogenesis. 0953-816x Journal Article}, Author = {Fabel, K. and Tam, B. and Kaufer, D. and Baiker, A. and Simmons, N. and Kuo, C. J. and Palmer, T. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Eur J Neurosci}, Keywords = {Bromodeoxyuridine/pharmacokinetics;Extracellular Matrix Proteins/pharmacology;Immunohistochemistry;Male;Mitotic Index/methods;Vascular Endothelial Growth Factor Receptor-2/metabolism;Animals;Blotting, Northern;Vascular Endothelial Growth Factor A/immunology/*physiology;04 Adult neurogenesis factors;Hippocampus/cytology/drug effects/metabolism/*physiology;Cell Count;Stem Cells/metabolism;Mice, Inbred C57BL;Tubulin/metabolism;Behavior, Animal;Support, U.S. Gov't, P.H.S.;Rats, Inbred F344;Comparative Study;Genistein/pharmacology;Running;C pdf;Enzyme Inhibitors/pharmacology;Rats;Dose-Response Relationship, Drug;Enzyme-Linked Immunosorbent Assay;Neurons/drug effects/*physiology;Microscopy, Confocal;Support, Non-U.S. Gov't;Mice;Physical Conditioning, Animal/*physiology;Reverse Transcriptase Polymerase Chain Reaction;Neuropilins/metabolism}, Number = {10}, Organization = {Department of Neurosurgery, Mail Code 5487, MSLS P309, 1201 Welch Rd, Stanford University, Stanford, CA 94305-5487, USA.}, Pages = {2803-12}, Pubmed = {14656329}, Title = {VEGF is necessary for exercise-induced adult hippocampal neurogenesis}, Uuid = {8BF9D87D-B88E-41E5-B025-400F7A76477A}, Volume = {18}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14656329}} @article{Fagiolini:2004, Abstract = {Weak inhibition within visual cortex early in life prevents experience-dependent plasticity. Loss of responsiveness to an eye deprived of vision can be initiated prematurely by enhancing gamma-aminobutyric acid (GABA)-mediated transmission with benzodiazepines. Here, we use a mouse "knockin" mutation to alpha subunits that renders individual GABA type A (GABA(A)) receptors insensitive to diazepam to show that a particular inhibitory network controls expression of the critical period. Only alpha1-containing circuits were found to drive cortical plasticity, whereas alpha2-enriched connections separately regulated neuronal firing. This dissociation carries implications for models of brain development and the safe design of benzodiazepines for use in infants.}, Author = {Fagiolini, Michela and Fritschy, Jean-Marc M. and L{\"o}w, Karin and M{\"o}hler, Hanns and Rudolph, Uwe and Hensch, Takao K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Diazepam;gamma-Aminobutyric Acid;Protein Subunits;Animals;Neuronal Plasticity;Synaptic Transmission;Mutation;Mice, Inbred C57BL;research support, non-u.s. gov't;Vision;Pyridines;Receptors, GABA-A;21 Neurophysiology;Neurons;Mice;Interneurons;24 Pubmed search results 2008;Dominance, Ocular;Models, Neurological;Neural Inhibition;Visual Cortex}, Month = {3}, Nlm_Id = {0404511}, Number = {5664}, Organization = {Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198 Japan.}, Pages = {1681-3}, Pii = {303/5664/1681}, Pubmed = {15017002}, Title = {Specific GABAA circuits for visual cortical plasticity}, Uuid = {026648A0-F59F-46A8-98A9-51A82EC4D9B7}, Volume = {303}, Year = {2004}, url = {papers/Fagiolini_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1091032}} @article{Fahrner:2006, Abstract = {Granule cell dispersion (GCD) in the dentate gyrus is a frequent feature of Ammon's horn sclerosis (AHS) which is often associated with temporal lobe epilepsy (TLE). It has been hypothesized that GCD may be caused by an abnormal migration of newly born granule cells. To test this hypothesis, we used markers of proliferation and neurogenesis and immunocytochemical methods as well as quantitative Western blot and real-time RT-PCR analyses in surgically resected hippocampi from TLE patients and controls. Below the age of 1 year, Ki-67-immunopositive nuclei were detected in the subgranular zone of the dentate gyrus, but not in the dentate of TLE patients independent of age. The expression of the proliferation marker minichromosome maintenance protein 2 (mcm2) and of doublecortin (DCX) decreased significantly with age in controls and in TLE patients, but the expression of both proteins was independent of the degree of AHS and GCD. Quantitative real-time RT-PCR confirmed these findings at the level of gene expression. In contrast, immunocytochemistry for glial fibrillary acidic protein (GFAP) and vimentin as well as Golgi staining revealed a radially aligned glial network in the region of GCD. GFAP-positive fiber length significantly increased with the severity of GCD. These results indicate that epileptic activity does not stimulate neurogenesis in the human dentate gyrus and that GCD probably does not result from a malpositioning of newly generated granule cells, but rather from an abnormal migration of mature granule cells along a radial glial scaffold.}, Author = {Fahrner, and Kann, and Flubacher, and Heinrich, and Freiman, and Zentner, and Frotscher, and Haas,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {10}, Nlm_Id = {0370712}, Organization = {Experimental Epilepsy Group, Neurocenter, University of Freiburg, Breisacher Strae 64, D-79106 Freiburg, Germany.}, Pii = {S0014-4886(06)00483-3}, Pubmed = {17049346}, Title = {Granule cell dispersion is not accompanied by enhanced neurogenesis in temporal lobe epilepsy patients}, Uuid = {981E1E17-1CD7-48D0-830A-BD2DC364FE7C}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2006.08.023}} @article{Fainzilber:2006, Abstract = {Wallerian degeneration of distal axons after nerve injury is significantly delayed in the Wlds mutant mouse. The Wlds protein is a fusion of nicotinamide mononucleotide adenyltransferase-1 (Nmnat1), an essential enzyme in the biosynthesis pathway of nicotinamide adenine dinucleotide (NAD), with the N-terminal 70 amino acids of the Ube4b ubiquitination assembly factor. The mechanism of Wlds action is still enigmatic, although recent efforts suggest that it is indirect and requires sequences flanking or linking the two fused open reading frames. Three papers in this issue of Neuron now show that Wlds action is conserved in Drosophila and that a critical role of Wlds may be the suppression of axonal self-destruct signals that induce Draper-mediated clearance of damaged axons by glial cells.}, Author = {Fainzilber, Mike and Twiss, Jeffery L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;research support, n.i.h., extramural ;Wallerian Degeneration;Membrane Proteins;research support, non-u.s. gov't ;Drosophila Proteins;Nerve Tissue Proteins;Nicotinamide-Nucleotide Adenylyltransferase;research support, u.s. gov't, non-p.h.s. ;comment;Sirtuins;Animals;Humans;10 Structural plasticity;review;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Biological Chemistry, Weizmann Institute of Science, 76100 Rehovot, Israel. mike.fainzilber\@weizmann.ac.il}, Pages = {819-21}, Pii = {S0896-6273(06)00416-8}, Pubmed = {16772165}, Title = {Tracking in the Wlds--the hunting of the SIRT and the luring of the Draper}, Uuid = {B6084E8E-E738-4AAF-85A0-977A0EE98C35}, Volume = {50}, Year = {2006}, url = {papers/Fainzilber_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.05.023}} @article{Fair:2007, Abstract = {Human attentional control is unrivaled. We recently proposed that adults depend on distinct frontoparietal and cinguloopercular networks for adaptive online task control versus more stable set control, respectively. During development, both experience-dependent evoked activity and spontaneous waves of synchronized cortical activity are thought to support the formation and maintenance of neural networks. Such mechanisms may encourage tighter "integration" of some regions into networks over time while "segregating" other sets of regions into separate networks. Here we use resting state functional connectivity MRI, which measures correlations in spontaneous blood oxygenation level-dependent signal fluctuations between brain regions to compare previously identified control networks between children and adults. We find that development of the proposed adult control networks involves both segregation (i.e., decreased short-range connections) and integration (i.e., increased long-range connections) of the brain regions that comprise them. Delay/disruption in the developmental processes of segregation and integration may play a role in disorders of control, such as autism, attention deficit hyperactivity disorder, and Tourette's syndrome.}, Author = {Fair, Damien A. and Dosenbach, Nico U. F. and Church, Jessica A. and Cohen, Alexander L. and Brahmbhatt, Shefali and Miezin, Francis M. and Barch, Deanna M. and Raichle, Marcus E. and Petersen, Steven E. and Schlaggar, Bradley L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Oxygen;research support, non-u.s. gov't;Adolescent;21 Neurophysiology;Adult;Magnetic Resonance Imaging;Cerebellum;comparative study;research support, n.i.h., extramural;Child;Humans;Nerve Net;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {33}, Organization = {Departments of Neurology, Washington University, St. Louis, MO 63110, USA. damien.fair\@wustl.edu}, Pages = {13507-12}, Pii = {0705843104}, Pubmed = {17679691}, Title = {Development of distinct control networks through segregation and integration}, Uuid = {18F75C20-4036-45AF-81FD-ECB8AA60D039}, Volume = {104}, Year = {2007}, url = {papers/Fair_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0705843104}} @article{Fallon:2000, Abstract = {The development of an in vivo procedure for the induction of massive proliferation, directed migration, and neurodifferentiation (PMD) in the damaged adult central nervous system would hold promise for the treatment of human neurodegenerative disorders such as Parkinson's disease. We investigated the in vivo induction of PMD in the forebrain of the adult rat by using a combination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic neurons and infusions of transforming growth factor alpha (TGFalpha) into forebrain structures. Only in animals with both lesion and infusion of TGFalpha was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed toward the region of the TGFalpha infusion site. Subsequently, increasing numbers of differentiated neurons were observed in the striatum. In behavioral experiments, there was a significant reduction of apomorphine-induced rotations in animals receiving the TGFalpha infusions. These results show that the brain contains stem cells capable of PMD in response to an exogenously administered growth factor. This finding has significant implications with respect to the development of treatments for both acute neural trauma and neurodegenerative diseases.}, Author = {Fallon, J. and Reid, S. and Kinyamu, R. and Opole, I. and Opole, R. and Baratta, J. and Korc, M. and Endo, T. L. and Duong, A. and Nguyen, G. and Karkehabadhi, M. and Twardzik, D. and Patel, S. and Loughlin, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:46 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Neurons/cytology/drug effects/metabolism/*physiology;Cell Differentiation;Rats, Sprague-Dawley;Transforming Growth Factor alpha/administration &dosage/genetics;Prosencephalon/*cytology/drug effects;Rats;D;06 Adult neurogenesis injury induced;Cell Division;Animal;Support, U.S. Gov't, P.H.S.;Cell Movement/*physiology;Support, Non-U.S. Gov't;Oxidopamine/administration &dosage;Male}, Number = {26}, Organization = {Departments of Anatomy and Neurobiology, Medicine, and Pharmacology, University of California, Irvine, CA 92697-1275, USA. jfallon\@uci.edu}, Pages = {14686-91.}, Title = {In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain}, Uuid = {867020E3-202B-4D0E-B995-79138F77F850}, Volume = {97}, Year = {2000}, url = {papers/Fallon_ProcNatlAcadSciUSA2000.pdf}} @article{Fan:2005, Abstract = {Our previous studies have shown that intracerebral administration of endotoxin, lipopolysaccharide (LPS), induces selective white matter injury and hypomyelination in the neonatal rat brain and that the LPS-induced brain injury is associated with activation of microglia. To test the hypothesis that inhibition of microglial activation may protect against LPS-induced white matter injury, we examined roles of minocycline, a putative suppressor of microglial activation, on LPS-induced brain injury in the neonatal rat. A stereotactic intracerebral injection of LPS (1 mg/kg) was performed in postnatal day 5 Sprague-Dawley rats and control rats were injected with sterile saline. Minocycline (45 mg/kg) was administered intraperitoneally 12 h before and immediately after LPS injection and then every 24 h for 3 days. Inflammatory responses, activation of microglia and brain injury were examined 1 and 3 days after LPS injection. LPS injection resulted in brain injury in selective brain areas, including bilateral ventricular enlargement, cell death at the sub- and periventricular areas, loss of O4+ and O1+ oligodendrocyte (OL) immunoreactivity and hypomyelination, as indicated by decreased myelin basic protein immunostaining, in the neonatal rat brain. Minocycline administration significantly attenuated LPS-induced brain injury in these rat brains. The protective effect of minocycline was associated with suppressed microglial activation as indicated by the decreased number of activated microglial cells following LPS stimulation and with consequently decreased elevation of interleukin 1beta and tumor necrosis factor-alpha concentrations induced by LPS and a reduced number of inducible nitric oxide synthase expressing cells. Protection of minocycline was also linked with the reduction in LPS-induced oxidative stress, as indicated by 4-hydroxynonenal positive OLs. The overall results suggest that reduction in microglial activation may protect the neonatal brain from LPS-induced white matter injury and inhibition of microglial activation might be an effective approach for the therapeutic treatment of infection-induced white matter injury.}, Author = {Fan, L-W W. and Pang, Y. and Lin, S. and Rhodes, P. G. and Cai, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Animals;Rats;Tumor Necrosis Factor-alpha;Brain;Neuroprotective Agents;Female;Microglia;Rats, Sprague-Dawley;Nitric-Oxide Synthase;Macrophage Activation;11 Glia;Lipopolysaccharides;Brain Diseases;Alpha;Male;Cerebral Ventricles;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Oxidative Stress;Interleukin-1;Minocycline;Anti-Bacterial Agents;Immunohistochemistry;Research Support, N.I.H., Extramural;Injections;Enzyme-Linked Immunosorbent Assay}, Nlm_Id = {7605074}, Number = {1}, Organization = {Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.}, Pages = {159-68}, Pii = {S0306-4522(05)00213-7}, Pubmed = {15893639}, Title = {Minocycline attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain}, Uuid = {D270FE50-A024-4A04-8E92-8A4D139EDFDD}, Volume = {133}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2005.02.016}} @article{Farbman:1998, Abstract = {Olfactory marker protein (OMP) is a phylogenetically conserved, 19-kDa, acidic, soluble protein found abundantly in mature olfactory sensory neurons. Its function has been enigmatic although recent evidence from studies on OMP null mice suggests that neurons lacking OMP exhibit altered physiological activity, including prolonged onset and recovery kinetics following stimulation. We have reported increased expression of OMP in individual surviving sensory neurons that have been deprived of their target, the olfactory bulb. Because olfactory epithelia deprived of their target also exhibit an increased rate of cell division we investigated the effect of recombinant OMP on cell division in organotypic cultures of fetal rat (embryonic day 19) epithelium grown for 3 days in vitro. After 3 days, cultures were given a 1-hr pulse of a mitotic marker, bromodeoxyuridine (BrdU), fixed and prepared for immunohistochemistry to determine the number of proliferating cells. We found a dose-dependent increase in the number of BrdU- positive cells/100-mm length of epithelium. The number of labeled cells increased incrementally, reached a plateau at 25 pM OMP/ml culture medium, 50\%higher than in cultures with no OMP added, and remained at that level at 50 and 100 pM doses. Controls included trypsinized OMP and addition of equivalent volumes of TRIS buffer lacking OMP. These results, taken together with previous studies on several growth factors indicate that regulation of neurogenesis in olfactory tissue is a multifactorial process and that OMP may play a role.}, Author = {Farbman, A. I. and Buchholz, J. A. and Walters, E. and Margolis, F. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Ann N Y Acad Sci}, Keywords = {Recombinant Proteins/pharmacology;Nerve Tissue Proteins/metabolism/*pharmacology;Rats;Olfactory Receptor Neurons/*cytology/metabolism;Dose-Response Relationship, Drug;Animal;Support, U.S. Gov't, P.H.S.;I abstr;Cell Differentiation/drug effects/physiology;Cells, Cultured;Mice;13 Olfactory bulb anatomy}, Organization = {Northwestern University, Evanston, Illinois 60208, USA. afarbman\@nwu.edu}, Pages = {248-51.}, Title = {Does olfactory marker protein participate in olfactory neurogenesis?}, Uuid = {0036C1E0-BDCA-4514-B1CD-79E6DB9E9BBD}, Volume = {855}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9929615}} @article{Farrell:1992, Abstract = {Despite the use of hemispherectomy in the treatment of medically refractory seizures since the early 1950's, few studies published have documented neuropathologic findings in the resected specimens. This report describes the neuropathologic findings in 38 children who underwent either hemispherectomy or multilobar cortical resection as treatment for medically intractable epilepsy between 1986 and 1990. Examination of the resected specimens revealed a variety of abnormalities which fell into four broad categories. Malformations or hamartomatous lesions were the dominant finding in 15 patients, whereas encephalomalacic lesions were the most prominent abnormality in 16; chronic pathogen-free encephalitits (Rasmussen's encephalitis) was present in 3 and an additional 3 children had Sturge-Weber-Dimitri syndrome. There were no gross or microscopic abnormalities in 1 patient. This report provides the first comprehensive description of the pathologic findings in a series of children with refractory epilepsy of varying types treated by hemispherectomy-multilobar resection.}, Author = {Farrell, M. A. and DeRosa, M. J. and Curran, J. G. and Secor, D. L. and Cornford, M. E. and Comair, Y. G. and Peacock, W. J. and Shields, W. D. and Vinters, H. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol}, Keywords = {Sturge-Weber Syndrome;10 Development;Magnetic Resonance Imaging;Child, Preschool;Encephalitis;Humans;Hamartoma;Child;Epilepsy;Infant;21 Dysplasia-heterotopia;Brain Neoplasms;research support, non-u.s. gov't;Encephalomalacia;Hypoxia, Brain;10 genetics malformation;21 Neurophysiology;research support, u.s. gov't, p.h.s.;Cerebral Cortex;Brain Ischemia;24 Pubmed search results 2008;research support, u.s. gov't, non-p.h.s.}, Nlm_Id = {0412041}, Number = {3}, Organization = {Department of Pathology, UCLA Medical Center 90024.}, Pages = {246-59}, Pubmed = {1557956}, Title = {Neuropathologic findings in cortical resections (including hemispherectomies) performed for the treatment of intractable childhood epilepsy}, Uuid = {111BA2D2-86AD-44C3-9711-582E6CC9613A}, Volume = {83}, Year = {1992}} @article{Fassati:2003, Abstract = {Human immunodeficiency virus type 1 (HIV-1), like other lentiviruses, can infect non-dividing cells. This property depends on the active nuclear import of its intracellular reverse transcription complex (RTC). We have studied nuclear import of purified HIV-1 RTCs in primary macrophages and found that importin 7, an import receptor for ribosomal proteins and histone H1, is involved in the process. Nuclear import of RTCs requires, in addition, energy and the components of the Ran system. Depletion of importin 7 from cultured cells by small interfering RNA inhibits HIV-1 infection. These results provide a new insight into the molecular mechanism for HIV-1 nuclear import and reveal potential targets for therapeutic intervention.}, Author = {Fassati, Ariberto and G{\"o}rlich, Dirk and Harrison, Ian and Zaytseva, Lyubov and Mingot, Jos{\'e}-Manuel M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0261-4189}, Journal = {EMBO J}, Keywords = {Transcription, Genetic;HIV-1;Humans;Macrophages;Cells, Cultured;Nuclear Envelope;HIV-1 Reverse Transcriptase;Mutation;Antigens, CD4;Karyopherins;15 Retrovirus mechanism;RNA, Small Interfering;ran GTP-Binding Protein;Hela Cells;HIV Infections;Active Transport, Cell Nucleus;Cell Nucleolus;Cell Nucleus;Receptors, CCR5;DNA, Viral;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {22737498}, Month = {7}, Nlm_Id = {8208664}, Number = {14}, Organization = {The Wohl Virion Centre, Windeyer Institute, University College London Medical School, 46 Cleveland Street, London W1T 4JF, UK. a.fassati\@ucl.ac.uk}, Pages = {3675-85}, Pubmed = {12853482}, Title = {Nuclear import of HIV-1 intracellular reverse transcription complexes is mediated by importin 7}, Uuid = {010D180F-E038-4459-BE82-F03C8039C98F}, Volume = {22}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/emboj/cdg357}} @article{Faulkner:2000, Abstract = {Mutations in the LIS1 gene cause gross histological disorganization of the developing human brain, resulting in a brain surface that is almost smooth. Here we show that LIS1 protein co-immunoprecipitates with cytoplasmic dynein and dynactin, and localizes to the cell cortex and to mitotic kinetochores, which are known sites for binding of cytoplasmic dynein. Overexpression of LIS1 in cultured mammalian cells interferes with mitotic progression and leads to spindle misorientation. Injection of anti-LIS1 antibody interferes with attachment of chromosomes to the metaphase plate, and leads to chromosome loss. We conclude that LIS1 participates in a subset of dynein functions, and may regulate the division of neuronal progenitor cells in the developing brain.}, Author = {Faulkner, N. E. and Dujardin, D. L. and Tai, C. Y. and Vaughan, K. T. and O'Connell, C. B. and Wang, Y. and Vallee, R. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {10 Development;Microtubule-Associated Proteins;Animals;Humans;Mitosis;research support, u.s. gov't, p.h.s. ;1-Alkyl-2-acetylglycerophosphocholine Esterase;Cercopithecus aethiops;Cytoplasm;COS Cells;research support, non-u.s. gov't ;Microtubules;Cell Line;Kinetochores;Subcellular Fractions;Dynein ATPase;Cell Division;24 Pubmed search results 2008;Dogs;Gene Expression;Precipitin Tests}, Month = {11}, Nlm_Id = {100890575}, Number = {11}, Organization = {Department of Cell Biology University of Massachusetts Medical School, 377 Plantation Street, Worcester, Massachusetts 01605, USA.}, Pages = {784-91}, Pubmed = {11056532}, Title = {A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function}, Uuid = {685D6C43-5E44-441F-A63C-3A62645C2E69}, Volume = {2}, Year = {2000}, url = {papers/Faulkner_NatCellBiol2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35041020}} @article{Faux:2001, Abstract = {The differentiation of precursor cells into neurons has been shown to be influenced by both the Notch signaling pathway and growth factor stimulation. In this study, the regulation of neuronal differentiation by these mechanisms was examined in the embryonic day 10 neuroepithelial precursor (NEP) population. By downregulating Notch1 expression and by the addition of a Delta1 fusion protein (Delta Fc), it was shown that signaling via the Notch pathway inhibited neuron differentiation in the NEP cells, in vitro. The expression of two of the Notch receptor homologs, Notch1 and Notch3, and the ligand Delta1 in these NEP cells was found to be influenced by a number of different growth factors, indicating a potential interaction between growth factors and Notch signaling. Interestingly, none of the growth factors examined promoted neuron differentiation; however, the fibroblast growth factors (FGFs) 1 and 2 potently inhibited differentiation. FGF1 and FGF2 upregulated the expression of Notch and decreased expression of Delta1 in the NEP cells. In addition, the inhibitory response of the cells to the FGFs could be overcome by downregulating Notch1 expression and by disrupting Notch cleavage and signaling by the ablation of the Presenilin1 gene. These results indicate that FGF1 and FGF2 act via the Notch pathway, either directly or indirectly, to inhibit differentiation. Thus, signaling through the Notch receptor may be a common regulator of neuronal differentiation within the developing forebrain.}, Author = {Faux, C. H. and Turnley, A. M. and Epa, R. and Cappai, R. and Bartlett, P. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {J Neurosci}, Keywords = {10 Development;Receptors, Cell Surface/genetics/metabolism;Neurons/cytology/*metabolism;Cells, Cultured;Mice, Mutant Strains;Down-Regulation (Physiology);Fibroblast Growth Factor, Basic/metabolism/pharmacology;Protein Binding/physiology;Cell Count;Animal;F pdf;Cell Differentiation/drug effects/*physiology;Signal Transduction/drug effects/physiology;Mice, Inbred CBA;Support, Non-U.S. Gov't;Immunoglobulins, Fc/genetics;Proto-Oncogene Proteins/genetics/metabolism;Stem Cells/cytology/drug effects/metabolism;Mice;Gene Expression/drug effects;inhibitors/deficiency/genetics/*metabolism/pharmacology;Blood Proteins/pharmacology;Fibroblast Growth Factor/*metabolism/pharmacology;Recombinant Fusion Proteins/genetics/metabolism;Oligonucleotides, Antisense/pharmacology;Membrane Proteins/antagonists &}, Number = {15}, Organization = {The Walter and Eliza Hall Institute of Medical Research, The Royal Melbourne Hospital, Victoria 3050, Australia.}, Pages = {5587-96.}, Title = {Interactions between fibroblast growth factors and Notch regulate neuronal differentiation}, Uuid = {897B8CBE-DBF0-4ADC-9468-6128A7E3ADB7}, Volume = {21}, Year = {2001}, url = {papers/Faux_JNeurosci2001}} @article{Farber:2006, Abstract = {In this review we summarize mechanisms of Ca(2+) signaling in microglial cells and the impact of Ca(2+) signaling and Ca(2+) levels on microglial function. So far, Ca(2+) signaling has been only characterized in cultured microglia and thus these data refer rather to activated microglia as observed in pathology when compared with the resting form found under physiological conditions. Purinergic receptors are the most prominently expressed ligand-gated Ca(2+)-permeable channels in microglia and control several microglial functions such as cytokine release in a Ca(2+)-dependent fashion. A large variety of metabotropic receptors are linked to Ca(2+) release from intracellular stores. Depletion of these intracellular stores triggers a capacitative Ca(2+) entry. While microglia are already in an activated state in culture, they can be further activated, for example, by exposure to bacterial endotoxin. This activation leads to a chronic increase of [Ca(2+)](i) and this Ca(2+) increase is a prerequisite for the release of nitric oxide and cytokines. Moreover, several factors (TNFalpha, IL-1beta, and IFN-gamma) regulate resting [Ca(2+)](i) levels. (c) 2006 Wiley-Liss, Inc.}, Author = {F{\"a}rber, and Kettenmann,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {14 Immune;11 Glia;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8806785}, Number = {7}, Organization = {Cellular Neuroscience, MaxDelbrueckCenter for Molecular Medicine, RobertR{\"o}ssleStra$\beta$e 10, 13092 Berlin, Germany.}, Pages = {656-665}, Pubmed = {17006894}, Title = {Functional role of calcium signals for microglial function}, Uuid = {235CC9B7-8023-4910-8E16-37722F559487}, Volume = {54}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20412}} @article{Fedoroff:1997, Abstract = {A marked effect of colony stimulating factor-1(CSF-1) on microglial response and neuron survival in cerebral cortex ischemic damage was observed. In osteopetrotic op/op mice, which lack systemically functional CSF-1 microglia do not respond to ischemic damage to the cerebral cortex, and the infarcts are considerably larger than in CSF-1 producing mice with similar vascular impairment. Delivery of extraneous CSF-1 to op/op mice alleviates the functional deficiency of the microglia and potentiates neuron survival in ischemic lesion. Delivery of extraneous recombinant CSF-1 to normal CSF-1 producing mice does not increase either the number or degree of activation of microglia, but does further potentiate neuronal survival. We found that neurons in the cerebral cortex have active CSF-1 receptors, and we therefore propose that neuronal rescue in cerebral cortex ischemic damage is linked to activation of the CSF-1 receptor on neurons.}, Author = {Fedoroff, S. and Berezovskaya, O. and Maysinger, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0149-7634}, Journal = {Neurosci Biobehav Rev}, Keywords = {Brain Ischemia;11 Glia;Cell Death;Colony-Stimulating Factors;review, tutorial;Support, Non-U.S. Gov't;Animals;Mice;review}, Medline = {97216773}, Month = {3}, Nlm_Id = {7806090}, Number = {2}, Organization = {Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.}, Pages = {187-91}, Pii = {S0149763496000097}, Pubmed = {9062942}, Title = {Role of colony stimulating factor-1 in brain damage caused by ischemia}, Uuid = {F420C84F-208D-4CA7-8C99-5D16D0ABCBB1}, Volume = {21}, Year = {1997}} @article{Feinberg:2008, Abstract = {The identification of synaptic partners is challenging in dense nerve bundles, where many processes occupy regions beneath the resolution of conventional light microscopy. To address this difficulty, we have developed GRASP, a system to label membrane contacts and synapses between two cells in living animals. Two complementary fragments of GFP are expressed on different cells, tethered to extracellular domains of transmembrane carrier proteins. When the complementary GFP fragments are fused to ubiquitous transmembrane proteins, GFP fluorescence appears uniformly along membrane contacts between the two cells. When one or both GFP fragments are fused to synaptic transmembrane proteins, GFP fluorescence is tightly localized to synapses. GRASP marks known synaptic contacts in C. elegans, correctly identifies changes in mutants with altered synaptic specificity, and can uncover new information about synaptic locations as confirmed by electron microscopy. GRASP may prove particularly useful for defining connectivity in complex nervous systems.}, Author = {Feinberg, Evan H. and Vanhoven, Miri K. and Bendesky, Andres and Wang, George and Fetter, Richard D. and Shen, Kang and Bargmann, Cornelia I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;10 circuit formation;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Howard Hughes Medical Institute, Laboratory of Neural Circuits and Behavior, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.}, Pages = {353-63}, Pii = {S0896-6273(07)01020-3}, Pubmed = {18255029}, Title = {GFP Reconstitution Across Synaptic Partners (GRASP) Defines Cell Contacts and Synapses in Living Nervous Systems}, Uuid = {9408D907-BB62-42D7-8EF1-165DA1E4DDFC}, Volume = {57}, Year = {2008}, url = {papers/Feinberg_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.11.030}} @article{Feinstein:2004, Abstract = {No models fully account for how odorant receptors (ORs) function in the guidance of axons of olfactory sensory neurons (OSNs) to glomeruli in the olfactory bulb. Here, we use gene targeting in mice to demonstrate that the OR amino acid sequence imparts OSN axons with an identity that allows them to coalesce into glomeruli. Replacements between the coding regions of the M71 and M72 OR genes reroute axons to their respective glomeruli. A series of M71-M72 hybrid ORs uncover a spectrum of glomerular phenotypes, leading to the concept that the identity of OSN axons is revealed depending on what other axons are present. Naturally occurring amino acid polymorphisms in other ORs also produce distinct axonal identities. These critical amino acid residues are distributed throughout the protein and reside predominantly within transmembrane domains. We propose a contextual model for axon guidance in which ORs mediate homotypic interactions between like axons.}, Author = {Feinstein, Paul and Mombaerts, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:46 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {13 Olfactory bulb anatomy;Cell Differentiation;Animals;Gene Targeting;Synapses;Gene Expression Regulation, Developmental;Olfactory Receptor Neurons;Phenotype;Models, Biological;Cell Membrane;Cell Communication;Mice, Transgenic;Open Reading Frames;Olfactory Bulb;Support, Non-U.S. Gov't;Protein Structure, Tertiary;Polymorphism (Genetics);Support, U.S. Gov't, P.H.S.;Receptors, Odorant;Mice;Growth Cones;Amino Acid Sequence}, Month = {6}, Nlm_Id = {0413066}, Number = {6}, Organization = {The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. feinstp\@rockefeller.edu}, Pages = {817-31}, Pii = {S0092867404004957}, Pubmed = {15186781}, Title = {A contextual model for axonal sorting into glomeruli in the mouse olfactory system}, Uuid = {53CE646C-22FA-49F4-8603-2D22759C7223}, Volume = {117}, Year = {2004}, url = {papers/Feinstein_Cell2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.05.011}} @article{Feinstein:2004a, Abstract = {Odorant receptors (ORs) provide the core determinant of identity for axons of olfactory sensory neurons (OSNs) to coalesce into glomeruli in the olfactory bulb. Here, using gene targeting in mice, we examine how the OR protein determines axonal identity. An OR::GFP fusion protein is present in axons, consistent with a direct function of ORs in axon guidance. When the OR coding region is deleted, we observe OSNs that coexpress other ORs that function in odorant reception and axonal identity. It remains unclear if such coexpression is normally prevented by negative feedback on OR gene choice. A drastic reduction in OR protein level produces axonal coalescence into novel, remote glomeruli. By contrast, chimeric ORs and ORs with minor mutations perturb axon outgrowth. Strikingly, the beta2 adrenergic receptor can substitute for an OR in glomerular formation when expressed from an OR locus. Thus, ORs have not evolved a unique function in axon guidance.}, Author = {Feinstein, Paul and Bozza, Thomas and Rodriguez, Ivan and Vassalli, Anne and Mombaerts, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:46 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {13 Olfactory bulb anatomy;Cell Differentiation;Animals;Gene Targeting;Synapses;Gene Expression Regulation, Developmental;Olfactory Receptor Neurons;Mutation;Cell Communication;Mice, Transgenic;Open Reading Frames;Recombinant Fusion Proteins;Olfactory Bulb;Support, Non-U.S. Gov't;Receptors, Adrenergic, beta-2;Alleles;Chimeric Proteins;Support, U.S. Gov't, P.H.S.;Receptors, Odorant;Cilia;Mice;Luminescent Proteins;Growth Cones}, Month = {6}, Nlm_Id = {0413066}, Number = {6}, Organization = {The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. feinstp\@rockefeller.edu}, Pages = {833-46}, Pii = {S0092867404005318}, Pubmed = {15186782}, Title = {Axon guidance of mouse olfactory sensory neurons by odorant receptors and the beta2 adrenergic receptor}, Uuid = {4987D273-9AE3-4FDA-AD75-51A0E25E1087}, Volume = {117}, Year = {2004}, url = {papers/Feinstein_Cell2004a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.05.013}} @article{Feller:1996, Abstract = {Highly correlated neural activity in the form of spontaneous waves of action potentials is present in the developing retina weeks before vision. Optical imaging revealed that these waves consist of spatially restricted domains of activity that form a mosaic pattern over the entire retinal ganglion cell layer. Whole-cell recordings indicate that wave generation requires synaptic activation of neuronal nicotinic acetylcholine receptors on ganglion cells. The only cholinergic cells in these immature retinas are a uniformly distributed bistratified population of amacrine cells, as assessed by antibodies to choline acetyltransferase. The results indicate that the major source of synaptic input to retinal ganglion cells is a system of cholinergic amacrine cells, whose activity is required for wave propagation in the developing retina.}, Author = {Feller, M. B. and Wellis, D. P. and Stellwagen, D. and Werblin, F. S. and Shatz, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Retina;Retinal Ganglion Cells;Animals;Ferrets;Bungarotoxins;Synaptic Transmission;Patch-Clamp Techniques;Pyridazines;Choline O-Acetyltransferase;research support, non-u.s. gov't;Calcium;Acetylcholine;Tubocurarine;Animals, Newborn;Action Potentials;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Nicotinic Antagonists;GABA Antagonists;Cadmium;Curare;24 Pubmed search results 2008;research support, u.s. gov't, non-p.h.s.;Receptors, Nicotinic;in vitro; retinal wave paper}, Month = {5}, Nlm_Id = {0404511}, Number = {5265}, Organization = {Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, 94720-3200, USA. marla\@violet.berkeley.edu}, Pages = {1182-7}, Pubmed = {8638165}, Title = {Requirement for cholinergic synaptic transmission in the propagation of spontaneous retinal waves}, Uuid = {6D588E9D-C1A9-404D-92E2-676BB1014EF0}, Volume = {272}, Year = {1996}, url = {papers/Feller_Science1996.pdf}} @article{Fellin:2006, Abstract = {The release of glutamate from astrocytes activates synchronous slow inward currents (SICs) in hippocampal pyramidal neurons, which are mediated by the NMDA receptor and represent a nonsynaptic mechanism to promote the synchronization of neuronal activity. Two recent studies demonstrate that SICs generate neuronal paroxysmal depolarizations resembling those typical of interictal epileptiform activity and proposed that there could be an astrocytic basis of epilepsy (Kang et al., 2005; Tian et al., 2005). We tested this hypothesis using two in vitro models of epileptiform activity in hippocampal slices. Removal of extracellular Mg2+ and application of picrotoxin or perfusion with 0.5 mM Mg2+ and 8.5 mM K+-containing saline result mainly in neuronal ictal- and interictal-like epileptiform activity, respectively. Although both models trigger epileptiform activity, astrocytic Ca2+ oscillations were increased only after slice perfusion with 0 mM Mg2+ and picrotoxin. The activation of astrocytic Ca2+ signaling correlates with an increased frequency of SICs, and, when paired neurons were within 100 microm of one another with synchronous neuronal Ca2+ elevations, the generation of synchronous neuronal depolarizations and action potential discharges. TTX blocked both ictal- and interictal-like epileptiform activity without affecting SICs or SIC-mediated neuronal synchronization. In contrast, NMDA receptor antagonists, which block SICs, did not prevent the generation of either ictal- or interictal-like events. Based on this clear-cut pharmacology, our data demonstrate that nonsynaptic glutamate release from astrocytes is not necessary for the generation of epileptiform activity in vitro, although we cannot exclude the possibility that it may modulate the strength of the ictal (seizure)-like event.}, Author = {Fellin, Tommaso and Gomez-Gonzalo, Marta and Gobbo, Sara and Carmignoto, Giorgio and Haydon, Philip G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Epilepsy;research support, n.i.h., extramural ;21 Neurophysiology;Biological Clocks;Cell Communication;Action Potentials;research support, non-u.s. gov't ;Astrocytes;Hippocampus;Mice, Inbred C57BL;Pyramidal Cells;Animals;Cells, Cultured;24 Pubmed search results 2008;Glutamic Acid;Mice}, Month = {9}, Nlm_Id = {8102140}, Number = {36}, Organization = {Silvio Conte Center for Integration at the Tripartite Synapse, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.}, Pages = {9312-22}, Pii = {26/36/9312}, Pubmed = {16957087}, Title = {Astrocytic glutamate is not necessary for the generation of epileptiform neuronal activity in hippocampal slices}, Uuid = {9E30BE97-7C14-4138-BCD4-9387A66924C3}, Volume = {26}, Year = {2006}, url = {papers/Fellin_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2836-06.2006}} @article{Fellin:2004, Abstract = {Fast excitatory neurotransmission is mediated by activation of synaptic ionotropic glutamate receptors. In hippocampal slices, we report that stimulation of Schaffer collaterals evokes in CA1 neurons delayed inward currents with slow kinetics, in addition to fast excitatory postsynaptic currents. Similar slow events also occur spontaneously, can still be observed when neuronal activity and synaptic glutamate release are blocked, and are found to be mediated by glutamate released from astrocytes acting preferentially on extrasynaptic NMDA receptors. The slow currents can be triggered by stimuli that evoke Ca2+ oscillations in astrocytes, including photolysis of caged Ca2+ in single astrocytes. As revealed by paired recording and Ca2+ imaging, a striking feature of this NMDA receptor response is that it occurs synchronously in multiple CA1 neurons. Our results reveal a distinct mechanism for neuronal excitation and synchrony and highlight a functional link between astrocytic glutamate and extrasynaptic NMDA receptors.}, Author = {Fellin, Tommaso and Pascual, Olivier and Gobbo, Sara and Pozzan, Tullio and Haydon, Philip G. and Carmignoto, Giorgio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {in vitro;Electric Stimulation;Astrocytes;Synapses;Calcium Signaling;Rats;Neural Pathways;Animals;Feedback;Cortical Synchronization;Glutamic Acid;Cell Communication;Hippocampus;Rats, Wistar;research support, non-u.s. gov't;research support, u.s. gov't, p.h.s.;Neurons;Membrane Potentials;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Istituto CNR di Neuroscienze, Universit\`{a} di Padova, viale G. Colombo 3, 35121, Italy.}, Pages = {729-43}, Pii = {S0896627304004994}, Pubmed = {15339653}, Title = {Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors}, Uuid = {9BD284C0-0F1A-4DE5-A0D2-1654C3EDA242}, Volume = {43}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.08.011}} @article{Fellous:2004, Abstract = {When a cortical neuron is repeatedly injected with the same fluctuating current stimulus (frozen noise) the timing of the spikes is highly precise from trial to trial and the spike pattern appears to be unique. We show here that the same repeated stimulus can produce more than one reliable temporal pattern of spikes. A new method is introduced to find these patterns in raw multitrial data and is tested on surrogate data sets. Using it, multiple coexisting spike patterns were discovered in pyramidal cells recorded from rat prefrontal cortex in vitro, in data obtained in vivo from the middle temporal area of the monkey (Buracas et al., 1998) and from the cat lateral geniculate nucleus (Reinagel and Reid, 2002). The spike patterns lasted from a few tens of milliseconds in vitro to several seconds in vivo. We conclude that the prestimulus history of a neuron may influence the precise timing of the spikes in response to a stimulus over a wide range of time scales.}, Author = {Fellous, Jean-Marc M. and Tiesinga, Paul H. E. and Thomas, Peter J. and Sejnowski, Terrence J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Electric Stimulation;Photic Stimulation;Prefrontal Cortex;Animals;Rats;Algorithms;Signal Processing, Computer-Assisted;Patch-Clamp Techniques;Rats, Sprague-Dawley;Cluster Analysis;Pyramidal Cells;research support, non-u.s. gov't ;Macaca mulatta;Action Potentials;21 Neurophysiology;Neurons;Temporal Lobe;24 Pubmed search results 2008;Cats;Fixation, Ocular;Electrodes, Implanted;Geniculate Bodies}, Month = {3}, Nlm_Id = {8102140}, Number = {12}, Organization = {Computational Neurobiology Laboratory, Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. fellous\@salk.edu}, Pages = {2989-3001}, Pii = {24/12/2989}, Pubmed = {15044538}, Title = {Discovering spike patterns in neuronal responses}, Uuid = {D9F71A83-02FA-4991-B738-CE23711E3741}, Volume = {24}, Year = {2004}, url = {papers/Fellous_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4649-03.2004}} @article{Feng:2000, Abstract = {We generated transgenic mice in which red, green, yellow, or cyan fluorescent proteins (together termed XFPs) were selectively expressed in neurons. All four XFPs labeled neurons in their entirety, including axons, nerve terminals, dendrites, and dendritic spines. Remarkably, each of 25 independently generated transgenic lines expressed XFP in a unique pattern, even though all incorporated identical regulatory elements (from the thyl gene). For example, all retinal ganglion cells or many cortical neurons were XFP positive in some lines, whereas only a few ganglion cells or only layer 5 cortical pyramids were labeled in others. In some lines, intense labeling of small neuronal subsets provided a Golgi-like vital stain. In double transgenic mice expressing two different XFPs, it was possible to differentially label 3 neuronal subsets in a single animal.}, Author = {Feng, G. and Mellor, R. H. and Bernstein, M. and Keller-Peck, C. and Nguyen, Q. T. and Wallace, M. and Nerbonne, J. M. and Lichtman, J. W. and Sanes, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Transgenes;Presynaptic Terminals;Animals;Synapses;research support, u.s. gov't, p.h.s. ;Axons;Mice, Transgenic;Antigens, Thy-1;Green Fluorescent Proteins;Color;Microscopy, Fluorescence;Dendrites;research support, non-u.s. gov't ;Cell Lineage;Neuromuscular Junction;Cerebral Cortex;Neurons;21 Neurophysiology;Light;Regulatory Sequences, Nucleic Acid;Mice;24 Pubmed search results 2008;Luminescent Proteins;Retinal Ganglion Cells}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.}, Pages = {41-51}, Pii = {S0896-6273(00)00084-2}, Pubmed = {11086982}, Title = {Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP}, Uuid = {07CC9EFF-9170-42FC-B0BB-B172E7263262}, Volume = {28}, Year = {2000}, url = {papers/Feng_Neuron2000.pdf}} @article{Feng:2001, Abstract = {To examine the in vivo function of presenilin-1 (PS1), we selectively deleted the PS1 gene in excitatory neurons of the adult mouse forebrain. These conditional knockout mice were viable and grew normally, but they exhibited a pronounced deficiency in enrichment- induced neurogenesis in the dentate gyrus. This reduction in neurogenesis did not result in appreciable learning deficits, indicating that addition of new neurons is not required for memory formation. However, our postlearning enrichment experiments lead us to postulate that adult dentate neurogenesis may play a role in the periodic clearance of outdated hippocampal memory traces after cortical memory consolidation, thereby ensuring that the hippocampus is continuously available to process new memories. A chronic, abnormal clearance process in the hippocampus may conceivably lead to memory disorders in the mammalian brain.}, Author = {Feng, R. and Rampon, C. and Tang, Y. P. and Shrom, D. and Jin, J. and Kyin, M. and Sopher, B. and Martin, G. M. and Kim, S. H. and Langdon, R. B. and Sisodia, S. S. and Tsien, J. Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Neuron}, Keywords = {Membrane Proteins/*deficiency/*genetics;Alzheimer Disease/genetics;Electrophysiology;Neurons/pathology;Memory/*physiology;Animal;C abstr;Mice, Transgenic;Mice, Inbred C57BL;Prosencephalon/*growth &development/pathology;Mice, Inbred CBA;Support, Non-U.S. Gov't;Mice, Knockout;RNA, Messenger/genetics/metabolism;Hippocampus/*growth &development/pathology;04 Adult neurogenesis factors;Amyloid beta-Protein Precursor/*analogs &derivatives/metabolism;Support, U.S. Gov't, P.H.S.;Mice;Memory Disorders/genetics/pathology/physiopathology;Brain Chemistry/genetics}, Number = {5}, Organization = {Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.}, Pages = {911-26.}, Title = {Deficient neurogenesis in forebrain-specific presenilin-1 knockout mice is associated with reduced clearance of hippocampal memory traces}, Uuid = {E4D9AA44-7777-4AE9-9DE8-7CC404832F16}, Volume = {32}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11738035}} @article{Feng:2006, Abstract = {Mutations in the human Filamin A (FLNA) gene disrupt neuronal migration to the cerebral cortex and cause cardiovascular defects. Complete loss of Flna in mice results in embryonic lethality with severe cardiac structural defects involving ventricles, atria, and outflow tracts, as well as widespread aberrant vascular patterning. Despite these widespread developmental defects, migration and motility of many cell types does not appear to be affected. Instead, Flna-null embryos display abnormal epithelial and endothelial organization and aberrant adherens junctions in developing blood vessels, heart, brain, and other tissues. Essential roles for FLNA in intercellular junctions provide a mechanism for the diverse developmental defects seen in patients with FLNA mutations.}, Author = {Feng, Yuanyi and Chen, Ming Hui and Moskowitz, Ivan P. and Mendonza, Ashley M. and Vidali, Luis and Nakamura, Fumihiko and Kwiatkowski, David J. and Walsh, Christopher A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {7505876}, Number = {52}, Organization = {*Division of Genetics and Department of Cardiology, Children's Hospital Boston, Boston, MA 02215.}, Pages = {19836-41}, Pii = {0609628104}, Pubmed = {17172441}, Title = {Filamin A (FLNA) is required for cell-cell contact in vascular development and cardiac morphogenesis}, Uuid = {AE2B8A9F-7FCC-40A2-9EDC-4EE55D453544}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0609628104}} @article{Ferezou:2002, Abstract = {Neocortical neurons expressing the serotonin 5-HT3 receptor (5-HT3R) were characterized in rat acute slices by using patch-clamp recordings combined with single-cell RT-PCR and histochemical labeling. The 5-HT3A receptor subunit was expressed selectively in a subset of GABAergic interneurons coexpressing cholecystokinin (CCK) and vasoactive intestinal peptide (VIP). The 5-HT3B subunit was never detected, indicating that 5-HT3Rs expressed by neocortical interneurons did not contain this subunit. In 5-HT3A-expressing VIP/CCK interneurons, serotonin induced fast membrane potential depolarizations by activating an inward current that was blocked by the selective 5-HT3R antagonist tropisetron. Furthermore, we observed close appositions between serotonergic fibers and the dendrites and somata of 5-HT3R-expressing neurons, suggestive of possible synaptic contacts. Indeed, in interneurons exhibiting rapid excitation by serotonin, local electrical stimulations evoked fast EPSCs of large amplitude that were blocked by tropisetron. Finally, 5-HT3R-expressing neurons were also excited by a nicotinic agonist, indicating that serotonergic and cholinergic fast synaptic transmission could converge onto VIP/CCK interneurons. Our results establish a clear correlation between the presence of the 5-HT3A receptor subunit in neocortical VIP/CCK GABAergic interneurons, its functional expression, and its synaptic activation by serotonergic afferent fibers from the brainstem raphe nuclei. 1529-2401 Journal Article}, Author = {Ferezou, I. and Cauli, B. and Hill, E. L. and Rossier, J. and Hamel, E. and Lambolez, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {J Neurosci}, Keywords = {Receptors, Serotonin/drug effects/genetics/*metabolism;Interneurons/cytology/drug effects/*metabolism;Protein Subunits;Animals;Synaptic Transmission/drug effects/physiology;In Vitro;Membrane Potentials/drug effects/physiology;Rats;Vasoactive Intestinal Peptide/*metabolism;T pdf;Serotonin/*metabolism/pharmacology;Patch-Clamp Techniques;23 Technique;Rats, Wistar;Nicotinic Agonists/pharmacology;Serotonin Antagonists/pharmacology;Receptors, Serotonin, 5-HT3;Neurons, Afferent/cytology/metabolism;Reverse Transcriptase Polymerase Chain Reaction;Support, Non-U.S. Gov't;Neocortex/cytology/metabolism;Cholecystokinin/*metabolism;Excitatory Postsynaptic Potentials/drug effects/physiology;gamma-Aminobutyric Acid/metabolism}, Number = {17}, Organization = {Laboratoire de Neurobiologie et Diversite Cellulaire, Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7637, Ecole Superieure de Physique et Chime Industrielles de la ville de Paris, 75005 Paris, France.}, Pages = {7389-97}, Title = {5-HT3 receptors mediate serotonergic fast synaptic excitation of neocortical vasoactive intestinal peptide/cholecystokinin interneurons}, Uuid = {FDDB3FF2-59DC-43C8-9121-DBC13209714F}, Volume = {22}, Year = {2002}, url = {papers/Ferezou_JNeurosci2002.pdf}} @article{Fernandez:1998, Abstract = {Homologies between vertebrate forebrain subdivisions are still uncertain. In particular the identification of homologs of the mammalian neocortex or the dorsal ventricular ridge (DVR) of birds and reptiles is still a matter of dispute. To get insight about the organization of the primordia of the main telencephalic subdivisions along the anteroposterior axis of the neural tube, a fate map of the dorsal prosencephalon was obtained in avian chimeras at the 8- to 9-somite stage. At this stage, the primordia of the pallium, DVR and striatum were located on the dorsal aspect of the prosencephalon and ordered caudorostrally along the longitudinal axis of the brain. Expression of homeobox-containing genes of the Emx, Dlx and Pax families were used as markers of anteroposterior developmental subdivisions of the forebrain in mouse, chick, turtle and frog. Their expression domains delineated three main telencephalic subdivisions in all species at the onset of neurogenesis: the pallial, intermediate and striatal neuroepithelial domains. The fate of the intermediate subdivisions diverged, however, between species at later stages of development. Homologies between forebrain subdivisions are proposed based on the conservation and divergence of these gene expression patterns. 0950-1991 Journal Article}, Author = {Fernandez, A. S. and Pieau, C. and Reperant, J. and Boncinelli, E. and Wassef, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Development}, Keywords = {Sequence Analysis, DNA;Tissue Distribution;Cloning, Molecular;Animals;Tissue Transplantation;Comparative Study;Telencephalon/*embryology;Models, Biological;Species Specificity;Time Factors;N;19 Neocortical evolution;Xenopus laevis;Support, Non-U.S. Gov't;Chick Embryo;Turtles;*Genes, Homeobox;Homeodomain Proteins/*biosynthesis/genetics;DNA-Binding Proteins/biosynthesis;Nuclear Proteins/biosynthesis;Mice;Vertebrates/embryology;Coturnix;Gene Expression}, Number = {11}, Organization = {CNRS URA 1414, Equipe Regionalisation Nerveuse, Ecole Normale Superieure, 46, rue d'Ulm 75230 PARIS Cedex 05 France.}, Pages = {2099-111}, Pubmed = {9570774}, Title = {Expression of the Emx-1 and Dlx-1 homeobox genes define three molecularly distinct domains in the telencephalon of mouse, chick, turtle and frog embryos: implications for the evolution of telencephalic subdivisions in amniotes}, Uuid = {723A02B4-D47A-43C6-8ECF-9AA15DE6681B}, Volume = {125}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9570774}} @article{Fernandez:1998a, Abstract = {OBJECTIVE: One hypothesis proposes that a pre-existing alteration of medial temporal lobe structures contributes to febrile convulsions and subsequent hippocampal sclerosis (HS) in patients with temporal lobe epilepsy (TLE) and antecedent febrile convulsions. It is possible that such a structural alteration does not always lead to convulsions and may also be present in clinically unaffected relatives. METHODS: We tested this hypothesis by MRI investigation of 23 members of two families, of whom 13 had experienced febrile convulsions and 10 had not. One member of each family with febrile convulsions subsequently developed TLE. We compared the right/left ratios of hippocampal volumes (RHV) with 23 age- and sex-matched controls. Additionally, two independent raters assessed hippocampal signal intensity and pattern in T2- and fluid-attenuated inversion recovery images. RESULTS: Both TLE patients showed left HS. All subjects with febrile convulsions who did not develop epilepsy and six clinically unaffected relatives also showed asymmetric RHV (>3 standard deviation) but a normal hippocampal signal intensity. In all of these subjects, the left hippocampus was smaller. Visual inspection of these smaller hippocampi revealed blurred internal pattern or flat hippocampal bodies or both in one family and smaller hippocampal heads in the other. The pattern of HS in TLE patients showed a structural correlation with the abnormalities seen in their relatives. One subject with febrile convulsions had additional subcortical heterotopias. CONCLUSION: These findings suggest a subtle, pre-existing hippocampal malformation that may facilitate febrile convulsions and contribute to the development of subsequent HS.}, Author = {Fern{\'a}ndez, G. and Effenberger, O. and Vinz, B. and Steinlein, O. and Elger, C. E. and D{\"o}hring, W. and Heinze, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {Seizures, Febrile;Magnetic Resonance Imaging;Adolescent;Adult;Research Support, Non-U.S. Gov't;Hippocampus;Family Health;Female;Epilepsy, Temporal Lobe;Middle Aged;Child;Male;Humans;Pedigree;Sclerosis}, Medline = {98226022}, Month = {4}, Nlm_Id = {0401060}, Number = {4}, Organization = {Department of Clinical Neurophysiology, Otto-von-Guericke University, Magdeburg, Germany.}, Pages = {909-17}, Pubmed = {9566371}, Title = {Hippocampal malformation as a cause of familial febrile convulsions and subsequent hippocampal sclerosis}, Uuid = {AD8B279D-A3E5-11DA-AB00-000D9346EC2A}, Volume = {50}, Year = {1998}} @article{Ferrarelli:2007, Abstract = {OBJECTIVE: High-density EEG during sleep represents a powerful new tool to reveal potential abnormalities in rhythm-generating mechanisms while avoiding confounding factors associated with waking activities. As a first step in this direction, the authors employed high-density EEG to explore whether sleep rhythms differ between schizophrenia subjects, healthy individuals, and a psychiatric control group with a history of depression. METHOD: Healthy comparison subjects (N=17), medicated schizophrenia patients (N=18), and subjects with a history of depression (N=15) were recruited. Subjects were recorded during the first sleep episode of the night with a 256-electrode high-density EEG. Recordings were analyzed for changes in EEG power spectra, power topography, and sleep-specific cortical oscillations. RESULTS: The authors found that the schizophrenia group had a significant reduction in centroparietal EEG power, from 13.75 to 15.00 Hz, in relation to both the comparison and depression groups. No significant difference in EEG power between the comparison and depression groups was identified. The authors also found a decrease in sleep spindle number, amplitude, duration, and integrated spindle activity in schizophrenia patients. Furthermore, integrated spindle activity had an effect size corresponding to 93.0\%or 90.2\%separation of the schizophrenia from the comparison or depression group. CONCLUSIONS: Sleep spindles are generated by the thalamic reticular nucleus in conjunction with specific thalamic nuclei and are modulated by corticothalamic and thalamocortical connections. The deficit in sleep spindles in schizophrenia subjects may reflect dysfunction in thalamic-reticular and thalamocortical mechanisms and could represent a biological marker of illness.}, Author = {Ferrarelli, Fabio and Huber, Reto and Peterson, Michael J. and Massimini, Marcello and Murphy, Michael and Riedner, Brady A. and Watson, Adam and Bria, Pietro and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0002-953X}, Journal = {Am J Psychiatry}, Keywords = {Adolescent;Humans;Middle Aged;Depressive Disorder;Neural Pathways;Diagnosis, Differential;comparative study;Parietal Lobe;Female;Schizophrenia;Sleep Stages;research support, non-u.s. gov't;Male;Sleep;Thalamus;Cerebral Cortex;21 Neurophysiology;Adult;Reticular Formation;24 Pubmed search results 2008;Biological Markers;Electroencephalography;Brain Mapping}, Month = {3}, Nlm_Id = {0370512}, Number = {3}, Organization = {University of Wisconsin, Department of Psychiatry, 6001 Research Park Blvd., Madison, WI 53719, USA.}, Pages = {483-92}, Pii = {164/3/483}, Pubmed = {17329474}, Title = {Reduced sleep spindle activity in schizophrenia patients}, Uuid = {7ADA1D26-82FF-48E2-9D56-E0F5F4620F90}, Volume = {164}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1176/appi.ajp.164.3.483}} @article{Ferrer:1993, Abstract = {Different cortical malformations were produced in rats by a single dose of X-rays (200 cGy) given on different days during gestation. These include large cortical ectopic masses after irradiation on day 14; segmentation of the cerebral cortex following irradiation on days 15, 17, 19; and a four-layered "lissencephalic" cortex following irradiation on day 16. Other types of cortical malformation were produced in rats aged 0-2 days by one of the following procedures: focal cortical freezing, focal electrocoagulation, cortical aspiration, and focal brushing of the meninges with a blunt needle covered with cotton. These latter abnormalities include laminar necrosis of layer V, focal cortical dysplasia reminiscent of microgyria, status verrucosus deformis and porencephaly. Experimentally induced cortical malformations in rats can help to increase our understanding of normal and abnormal neurogenesis and organisation of the human cerebral cortex.}, Author = {Ferrer, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0256-7040}, Journal = {Childs Nerv Syst}, Keywords = {Disease Models, Animal;Gestational Age;21 Epilepsy;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Inhalation;Electrocoagulation;Female;Fetal Diseases;Rats, Wistar;Pregnancy;Animals;Radiation Injuries, Experimental;24 Pubmed search results 2008;Freezing;Cerebral Cortex}, Medline = {94138960}, Month = {11}, Nlm_Id = {8503227}, Number = {7}, Organization = {Unidad Neuropatolog{\'\i}a, Servicio Anatom{\'\i}a Patol{\'o}gica, Hospital Pr{\'\i}ncipes de Espa\~{n}a, Universidad de Barcelona, Hospitalet de Llobregat, Spain.}, Pages = {403-7}, Pubmed = {8306356}, Title = {Experimentally induced cortical malformations in rats}, Uuid = {7D2ACF23-19E8-43D6-9F49-625172276D64}, Volume = {9}, Year = {1993}} @article{Ferrer:1993a, Abstract = {Different types of cortical malformation were produced, following focal cortical freezing, electrocoagulation, focal cortical aspiration or gentle brushing of uncovered meninges, in newborn or 1- to 3-day-old rats. Malformations included laminar necrosis of the cerebral cortex, status verrucosus, focal cortical dysplasia reminiscent of microgyria, and porencephaly. Similar procedures from postnatal day 4 onwards, at a time when a reactive astrogliosis is possible, produced cavitating infarcts and tissue scars. Cytoarchitectonic studies revealed an abnormal distribution of different types of pyramidal and non-pyramidal neurons in these malformations. These indicated three subtypes of focal cortical dysplasia, which probably depend on different pathogenic mechanisms. Autoradiographic studies with [3H] methylthymidine showed normal positioning of late-generated neuroblasts in the cerebral cortex, thus suggesting preserved migration. The present experimentally induced cortical malformations are useful models of similar cortical abnormalities in humans.}, Author = {Ferrer, I. and Alc{\'a}ntara, S. and Catal{\'a}, I. and Z{\'u}jar, M. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Animals;Meninges;Rats;Brain;21 Epilepsy;Thymidine;Rats, Wistar;Disease Models, Animal;Animals, Newborn;Cerebral Cortex;Freezing;Neurons;21 Neurophysiology;Parvalbumins;24 Pubmed search results 2008;Autoradiography;Tritium;Necrosis;Biological Markers;Research Support, Non-U.S. Gov't}, Medline = {93365596}, Nlm_Id = {0043312}, Number = {2}, Organization = {Unidad Neuropatolog{\'\i}a, Hospital Pr{\'\i}ncipes de Espa\~{n}a, Universidad de Barcelona, Hospitalet de Llobregat, Spain.}, Pages = {261-9}, Pubmed = {8359242}, Title = {Experimentally induced laminar necrosis, status verrucosus, focal cortical dysplasia reminiscent of microgyria, and porencephaly in the rat}, Uuid = {F9982979-C05A-4473-9631-AB37EF69555D}, Volume = {94}, Year = {1993}} @article{Ferrer:1996, Abstract = {Transforming growth factor alpha (TGF-alpha) and epidermal growth factor-receptor (EGF-R) immunoreactivity is observed in the majority of neurons, and in maturing astrocytes, in the developing and adult brain of humans and different species of animals. TGF-alpha and EGF-R co-localize in most neurons and maturing astrocytes, suggesting that most TGF-alpha-producing cells are EGF-R-expressing cells. TGF-alpha and EGF-R immunoreactivity decrease in damaged areas following different insults. However, EGF-R appears in reactive glia, mostly reactive astrocytes, within and surrounding the damaged areas. TGF-alpha and EGF-R immunoreactivity is found in neurons of patients affected by Alzheimer's disease and other forms of dementia, and in neurons of patients suffering from epilepsy owing to different causes, thus pointing to the conclusion that TGF-alpha does not play a significant role in these pathologies. However, EGF-R immunoreactivity occurs in reactive astrocytes and microglia in subacute but not chronic lesions in human cases. Since TGF-alpha is a membrane-anchored growth factor, which may be cleaved leading to the formation of soluble forms, and both the membrane-anchored and soluble forms have the capacity to activate the EGF-R, it is feasible that TGF-alpha in the nervous system may act upon EGF-R-containing neurons through different mechanisms. In addition to distant effects resulting from the release of soluble TGF-alpha, local effects may be produced by establishing direct cell-to-cell contacts (juxtacrine stimulation), or in cells expressing both TGF-alpha and EGF-R (autocrine stimulation).}, Author = {Ferrer, I. and Alc{\'a}ntara, S. and Ballabriga, J. and Oliv{\'e}, M. and Blanco, R. and Rivera, R. and Carmona, M. and Berruezo, M. and Pitarch, S. and Planas, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {Receptor, Epidermal Growth Factor;Research Support, Non-U.S. Gov't;Alpha;11 Glia;Antibody Specificity;Transforming Growth Factor alpha;review, tutorial;Humans;Brain;Animals;review;Brain Chemistry}, Medline = {97001830}, Month = {6}, Nlm_Id = {0370121}, Number = {2}, Organization = {Unitat de Neuropatologia, Hospital Princeps d'Espanya, Universitat de Barcelona, Spain.}, Pages = {99-123}, Pii = {S0301008296000093}, Pubmed = {8844822}, Title = {Transforming growth factor-alpha (TGF-alpha) and epidermal growth factor-receptor (EGF-R) immunoreactivity in normal and pathologic brain}, Uuid = {C7FC955C-CC13-42FF-8A3F-6566D5D7AF9B}, Volume = {49}, Year = {1996}} @article{Ferri:2004, Abstract = {In many species, the Sox2 transcription factor is a marker of the nervous system from the beginning of its development, and we have previously shown that Sox2 is expressed in embryonic neural stem cells. It is also expressed in, and is essential for, totipotent inner cell mass stem cells and other multipotent cell lineages, and its ablation causes early embryonic lethality. To investigate the role of Sox2 in the nervous system, we generated different mouse mutant alleles: a null allele (Sox2(beta-geo) 'knock-in'), and a regulatory mutant allele (Sox2(DeltaENH)), in which a neural cell-specific enhancer is deleted. Sox2 is expressed in embryonic early neural precursors of the ventricular zone and, in the adult, in ependyma (a descendant of the ventricular zone). It is also expressed in the vast majority of dividing precursors in the neurogenic regions, and in a small proportion of differentiated neurones, particularly in the thalamus, striatum and septum. Compound Sox2(beta-geo/DeltaENH) heterozygotes show important cerebral malformations, with parenchymal loss and ventricle enlargement, and L-dopa-rescuable circling behaviour and epilepsy. We observed striking abnormalities in neurones; degeneration and cytoplasmic protein aggregates, a feature common to diverse human neurodegenerative diseases, are observed in thalamus, striatum and septum. Furthermore, ependymal cells show ciliary loss and pathological lipid inclusions. Finally, precursor cell proliferation and the generation of new neurones in adult neurogenic regions are greatly decreased, and GFAP/nestin-positive hippocampal cells, which include the earliest neurogenic precursors, are strikingly diminished. These findings highlight a crucial and unexpected role for Sox2 in the maintenance of neurones in selected brain areas, and suggest a contribution of neural cell proliferative defects to the pathological phenotype. 0950-1991 Journal article}, Author = {Ferri, A. L. and Cavallaro, M. and Braida, D. and Di Cristofano, A. and Canta, A. and Vezzani, A. and Ottolenghi, S. and Pandolfi, P. P. and Sala, M. and DeBiasi, S. and Nicolis, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {Development}, Keywords = {04 Adult neurogenesis factors;C pdf flathead mutant}, Title = {Sox2 deficiency causes neurodegeneration and impaired neurogenesis in the adult mouse brain}, Uuid = {7F0A3878-57A1-4BA0-820A-032F1EF97E47}, Year = {2004}, url = {papers/Ferri_Development2004.pdf}} @article{Fetler:2005, Author = {Fetler, Luc and Amigorena, Sebastian}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Receptors, Purinergic P2;Adenosine Triphosphate;Brain Injuries;Cells, Cultured;Movement;Capillaries;Astrocytes;11 Glia;Mice, Transgenic;Photons;Microglia;Cell Surface Extensions;Animals;Brain;Phagocytosis;Mice;Microscopy}, Month = {7}, Nlm_Id = {0404511}, Number = {5733}, Organization = {Laboratoire Physico-Chimie Curie, CNRS UMR 168, Institut Curie, Paris, France. luc.fetler\@curie.fr}, Pages = {392-3}, Pii = {309/5733/392}, Pubmed = {16020721}, Title = {Neuroscience. Brain under surveillance: the microglia patrol}, Uuid = {43BC98C6-CD87-4154-9045-6ADA42956C08}, Volume = {309}, Year = {2005}, url = {papers/Fetler_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1114852}} @article{Figlewicz:1988, Abstract = {In the course of development, corticocortical axons seem to first appear in a labile state from which they either mature into a stable state or are eliminated. These state transitions may be related to cytoskeletal modifications. By immunohistochemistry and immunobiochemistry we found that, in the corpus callosum of the cat, the heavy (200 kDa) subunit of neurofilaments (NF) becomes progressively more visible during the first postnatal month. This aspect of cytoskeletal maturation parallels the developmental loss of callosal axons, i.e. probably the stabilization of the axons which are not eliminated. A similar maturation of the heavy subunit was observed in the visual cortical areas 17 and 18. The medium (150 kDa) and to a lesser extent the light (70 kDa) NF subunits are already present a few days after birth.}, Author = {Figlewicz, D. A. and Gremo, F. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Aging;Macromolecular Systems;Antibodies;Cytoskeleton;Cats;Neurofilament Proteins;Antibodies, Monoclonal;Not relevant;11 Glia;Intermediate Filaments;Fluorescent Antibody Technique;Support, Non-U.S. Gov't;Molecular Weight;Intermediate Filament Proteins;Animals;Corpus Callosum}, Medline = {89118978}, Month = {8}, Nlm_Id = {0045503}, Number = {2}, Organization = {Service de Neurologie, CHUV, Lausanne, Switzerland.}, Pages = {181-9}, Pubmed = {3146406}, Title = {Differential expression of neurofilament subunits in the developing corpus callosum}, Uuid = {10C043D4-C1B6-4C45-A19B-5338A1873D61}, Volume = {470}, Year = {1988}} @article{Filipkowski:2005, Abstract = {In the central nervous system (CNS) generation of new neurons continues throughout adulthood, when it is limited to the olfactory bulb and hippocampus. The knowledge regarding the function of newly-generated neurons remains limited and is vigorously investigated using diverse approaches. Among these are genetically modified mice, most of them of knock-out type (KO). Results from 23 diverse KO mouse models demonstrate the importance of particular proteins (growth factors, nitric oxide synthases, receptors, cyclins/cyclin-associated proteins, transcription factors, etc.) in adult neurogenesis (ANGE) as well as separate it from developmental neurogenesis. These results bring us closer to revealing the function of newly generated neurons in adult brains.}, Author = {Filipkowski, Robert K. and Kiryk, Anna and Kowalczyk, Anna and Kaczmarek, Leszek}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0001-527X}, Journal = {Acta Biochim Pol}, Keywords = {24 Pubmed search results 2008}, Nlm_Id = {14520300R}, Number = {2}, Organization = {Laboratory of Molecular Neurobiology, Department of Molecular and Cellular Neurobiology, Nencki Institute, Warszawa, Poland.}, Pages = {359-72}, Pii = {055202359}, Pubmed = {15990921}, Title = {Genetic models to study adult neurogenesis}, Uuid = {6A17A3E1-5502-4ED0-A87D-9B1134D4DDD9}, Volume = {52}, Year = {2005}} @article{Filippov:2003, Abstract = {Based on the expression of glial fibrillary acidic protein (GFAP), a recent hypothesis considered stem or progenitor cells in the adult hippocampus to be a type of astrocyte. In a complementary approach, we used transgenic mice expressing green fluorescent protein (GFP) under the promoter for nestin, an intermediate filament present in progenitor cells, to demonstrate astrocytic features in nestin-GFP-positive cells. Morphologically, two subpopulations of nestin-GFP-positive cells were distinguishable; one had an elaborate tree of processes in the granule cell layer and expression of GFAP (but not of S100beta, another astrocytic marker). Electron microscopy revealed vascular end feet of nestin-positive cells, further supporting astrocytic differentiation. Electrophysiological examination of nestin-GFP-positive cells on acutely isolated hippocampal slices showed passive current characteristics of astrocytes in one subset of cells. Among the nestin-GFP-expressing cells with lacking astrocytic features, two cell types could be identified electrophysiologically: cells with delayed-rectifying potassium currents and a very small number of cells with sodium currents, potentially representing signs of the earliest steps of neuronal differentiation.}, Author = {Filippov, Vitali and Kronenberg, Golo and Pivneva, Tatjyana and Reuter, Katja and Steiner, Barbara and Wang, Li Ping and Yamaguchi, Masahiro and Kettenmann, Helmut and Kempermann, Gerd}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {Fluorescent Dyes;10 Development;10 Hippocampus;Animals;Astrocytes;Microscopy, Immunoelectron;Mice, Transgenic;Green Fluorescent Proteins;Potassium Channels;Capillaries;Dentate Gyrus;Membrane Potentials;Age Factors;Intermediate Filament Proteins;Mice;Isoquinolines;Luminescent Proteins;Stem Cells;Nerve Tissue Proteins;24 Pubmed search results 2008;Promoter Regions (Genetics);Research Support, Non-U.S. Gov't}, Medline = {22722094}, Month = {7}, Nlm_Id = {9100095}, Number = {3}, Organization = {Max Delbr{\"u}ck Center for Molecular Medicine (MDS) Berlin-Buch, Robert-R{\"o}ssle-Strasse 10, 13125 Berlin, Germany.}, Pages = {373-82}, Pii = {S1044743103000605}, Pubmed = {12837622}, Title = {Subpopulation of nestin-expressing progenitor cells in the adult murine hippocampus shows electrophysiological and morphological characteristics of astrocytes}, Uuid = {65CE90B1-5941-4768-850B-D0F75D5AD631}, Volume = {23}, Year = {2003}} @article{Fincher:1996, Abstract = {Excess sleep and fever are central nervous system (CNS) facets of the acute phase response; these responses are induced by microbial products, such as muramyl peptides, via their ability to enhance cytokine production. Although peripheral macrophages are known to digest bacteria, thereby releasing muramyl peptides that, in turn, stimulate cytokine production, it was unknown whether CNS phagocytes such as microglia also had this capacity. Primary cultures of microglia were allowed to phagocytize and digest Staphylococcus aureus radiolabeled with a cell wall-specific marker. Radiolabeled low molecular weight substances released into the culture medium were partially purified and tested for the ability to induce excess sleep, fever, and cytokine production. These substances increased non-rapid eye movement sleep, electroencephalographic slow-wave activity, and brain temperature after intracerebroventricular injection into rabbits. They also induced interleukin-1, tumor necrosis factor, and the interleukin-1 receptor antagonist production in human monocytes. Results suggest that microglia perform fundamental macrophage functions and further implicate microglia as resident immunocompetent cells.}, Author = {Fincher, E. F. and Johannsen, L. and Kap{\'a}s, L. and Takahashi, S. and Krueger, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0002-9513}, Journal = {Am J Physiol}, Keywords = {Mice, Inbred BALB C;Rabbits;Phagocytosis;Animals;Latex;Monocytes;Cell Extracts;Humans;Cells, Cultured;Research Support, U.S. Gov't, Non-P.H.S.;Microglia;Fever;11 Glia;Microscopy, Fluorescence;Male;Sleep;Microspheres;Research Support, U.S. Gov't, P.H.S.;Staphylococcus aureus;Molecular Weight;Mice;Cytokines}, Medline = {96331499}, Month = {7}, Nlm_Id = {0370511}, Number = {1 Pt 2}, Organization = {Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.}, Pages = {R149-56}, Pubmed = {8760216}, Title = {Microglia digest Staphylococcus aureus into low molecular weight biologically active compounds}, Uuid = {D8599E16-7DAC-4B32-B1BB-DEF35C726885}, Volume = {271}, Year = {1996}} @article{Finlay:1995, Abstract = {Analysis of data collected on 131 species of primates, bats, and insectivores showed that the sizes of brain components, from medulla to forebrain, are highly predictable from absolute brain size by a nonlinear function. The order of neurogenesis was found to be highly conserved across a wide range of mammals and to correlate with the relative enlargement of structures as brain size increases, with disproportionately large growth occurring in late-generated structures. Because the order of neurogenesis is conserved, the most likely brain alteration resulting from selection for any behavioral ability may be a coordinated enlargement of the entire nonolfactory brain. 0036-8075 Journal Article}, Author = {Finlay, B. L. and Darlington, R. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Science}, Keywords = {Human;Animals;Regression Analysis;Neurons/*cytology;Databases, Factual;Models, Statistical;Brain/*anatomy &histology/cytology/growth &development;*Evolution;Species Specificity;N;19 Neocortical evolution;Analysis of Variance;Adaptation, Physiological;Mammals/*anatomy &histology;Support, U.S. Gov't, P.H.S.;Cell Division;Primates/anatomy &histology;Insectivora/anatomy &histology;Models, Neurological;Chiroptera/anatomy &histology}, Number = {5217}, Organization = {Department of Psychology, Uris Hall, Cornell University, Ithaca, NY 14853, USA.}, Pages = {1578-84}, Pubmed = {7777856}, Title = {Linked regularities in the development and evolution of mammalian brains}, Uuid = {084E7463-9632-477B-804E-BF517324291A}, Volume = {268}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7777856}} @article{Firestein:2005, Author = {Firestein, Stuart}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Olfactory Pathways;Smell;History, 20th Century;Nobel Prize;Neurosciences;historical article;Gene Expression Profiling;biography;Animals;History, 21st Century;13 Olfactory bulb anatomy;Humans;Receptors, Odorant}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA. stuart\@biology.columbia.edu}, Pages = {333-8}, Pii = {S0896-6273(05)00053-X}, Pubmed = {15694319}, Title = {A nobel nose: the 2004 Nobel Prize in Physiology and Medicine}, Uuid = {B5FFFD0A-8512-4B84-84C2-DDB1B6B25B4F}, Volume = {45}, Year = {2005}, url = {papers/Firestein_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.01.021}} @article{Fischer:1972, Author = {Fischer, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0008-7335}, Journal = {Cas Lek Cesk}, Keywords = {Epilepsy;Cerebral Cortex;24 Pubmed search results 2008;21 Epilepsy;21 Neurophysiology;Rats;Gelatin;Electrophysiology;Ganglia;Animals;Disease Models, Animal;Neurons;Cobalt}, Medline = {72258774}, Month = {8}, Nlm_Id = {0004743}, Number = {33}, Pages = {772-7}, Pubmed = {5052540}, Title = {[Experimental cobalt-gelatinous epileptogenic focus in the brain cortex of rat]}, Uuid = {4E1D8EBB-08E0-442B-BDE4-D1E5FF89C7E6}, Volume = {111}, Year = {1972}} @article{Fischer:2001a, Abstract = {Microglia subpopulations were studied in mouse experimental autoimmune encephalomyelitis and toxoplasmic encephalitis. CNS inflammation was associated with the proliferation of CD11b(+) brain cells that exhibited the dendritic cell (DC) marker CD11c. These cells constituted up to 30\%of the total CD11b(+) brain cell population. In both diseases CD11c(+) brain cells displayed the surface phenotype of myeloid DC and resided at perivascular and intraparenchymatic inflammatory sites. By lacking prominent phagocytic organelles, CD11c(+) cells from inflamed brain proved distinct from other microglia, but strikingly resembled bone marrow-derived DC and thus were identified as DC. This brain DC population comprised cells strongly secreting IL-12p70, whereas coisolated CD11c(-) microglia/brain macrophages predominantly produced TNF-alpha, GM-CSF, and NO. In comparison, the DC were more potent stimulators of naive or allogeneic T cell proliferation. Both DC and CD11c(-) microglia/macrophages from inflamed brain primed naive T cells from DO11.10 TCR transgenic mice for production of Th1 cytokines IFN-gamma and IL-2. Resting microglia that had been purified from normal adult brain generated immature DC upon exposure to GM-CSF, while CD40 ligation triggered terminal maturation. Consistently, a functional maturation of brain DC was observed to occur following the onset of encephalitis. In conclusion, these findings indicate that in addition to inflammatory macrophage-like brain cells, intraparenchymatical DC exist in autoimmune and infectious encephalitis. These DC functionally mature upon disease onset and can differentiate from resident microglia. Their emergence, maturation, and prolonged activity within the brain might contribute to the chronicity of intracerebral Th1 responses.}, Author = {Fischer, H. G. and Reichmann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {Cell Differentiation;Granulocyte-Macrophage Colony-Stimulating Factor;Th1 Cells;T-Lymphocyte Subsets;Immunophenotyping;Brain;Cells, Cultured;Interphase;Lymphocyte Activation;Animals;Macrophage-1 Antigen;Toxoplasmosis, Animal;Mice, Inbred BALB C;Cell Aging;Mice, Inbred C57BL;Integrin alphaXbeta2;Dendritic Cells;Macrophages;CD40 Ligand;11 Glia;Leukocytes, Mononuclear;Comparative Study;Nitric Oxide;Leukocyte Count;Coculture Techniques;Female;Microglia;Cytokines;Encephalomyelitis, Autoimmune, Experimental;Mice;Research Support, Non-U.S. Gov't;Mice, Transgenic}, Medline = {21103309}, Month = {2}, Nlm_Id = {2985117R}, Number = {4}, Organization = {Institute for Medical Microbiology and Virology, Heinrich Heine University, Duesseldorf, Germany. hans-georg.fischer\@uni-duesseldorf.de}, Pages = {2717-26}, Pubmed = {11160337}, Title = {Brain dendritic cells and macrophages/microglia in central nervous system inflammation}, Uuid = {D4D34E3F-D8D0-470C-A684-B448B6653302}, Volume = {166}, Year = {2001}} @article{Fischer:2001, Abstract = {The retina of warm-blooded vertebrates is believed to be incapable of neural regeneration. Here we provide evidence that the retina of postnatal chickens has the potential to generate new neurons. In response to acute damage, numerous Muller glia re-entered the cell cycle, and shortly thereafter, expressed CASH-1, Pax6 and Chx10, transcription factors expressed by embryonic retinal progenitors. These progenitor-like cells transiently expressed neurofilament. Newly formed cells became distributed throughout the inner and outer nuclear layers of the retina, and remained for at least three weeks after damage. Some of these newly formed cells differentiated into retinal neurons, a few formed Muller glia, and most remained undifferentiated, with continued expression of Pax6 and Chx10. These cells continued to proliferate when grown in culture, with some differentiating into retinal neurons or Muller glia. We propose that, in response to damage, Muller glia in the retina are a potential source of neural regeneration.}, Author = {Fischer, A. J. and Reh, T. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Nat Neurosci}, Keywords = {Neuroglia/cytology/*metabolism;Nerve Regeneration/*physiology;N-Methylaspartate/pharmacology;Bromodeoxyuridine/pharmacology;Cells, Cultured/drug effects/metabolism;DNA-Binding Proteins/drug effects/metabolism;Neurons/cytology/*metabolism;Animal;Transcription Factors/drug effects/metabolism;Cell Division/drug effects/physiology;Receptors, Retinoic Acid/drug effects/metabolism;Retina/cytology/*metabolism;Support, Non-U.S. Gov't;Homeodomain Proteins/drug effects/metabolism;Neurotoxins/pharmacology;06 Adult neurogenesis injury induced;Neurofilament Proteins/drug effects/metabolism;D-13;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Glutamate-Ammonia Ligase/metabolism;Chickens}, Number = {3}, Organization = {Department of Biological Structure, University of Washington School of Medicine, Health Science Center, PO Box 357420, Seattle, Washington 98195, USA.}, Pages = {247-52.}, Title = {Muller glia are a potential source of neural regeneration in the postnatal chicken retina}, Uuid = {2BABCDFF-41CF-4419-87B9-4B39597517CD}, Volume = {4}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11224540}} @article{Fischer:2005, Abstract = {While deregulation of cyclin-dependent kinase 5 (Cdk5) has been implicated in neurodegenerative diseases, its precise role in synaptic plasticity and memory remains elusive. Proteolytic cleavage of p35, a regulatory subunit of Cdk5, by calpain results in the generation of the truncated p25 protein, which causes hyperactivation of Cdk5. Using region-specific and inducible transgenic mice, we show that transiently increased p25 expression in the hippocampus enhanced long-term potentiation (LTP) and facilitated hippocampus-dependent memory. Moreover, p25 expression increased the number of dendritic spines and synapses. Importantly, enhanced memory achieved by a transient expression of p25 followed by its repression did not cause neurodegeneration. In contrast, prolonged p25 production caused severe cognitive deficits, which were accompanied by synaptic and neuronal loss and impaired LTP. Our data suggest a role for p25 in synaptic plasticity, synaptogenesis, learning, and memory and provide a model whereby deregulation of a plasticity factor can contribute to neurodegeneration.}, Author = {Fischer, Andre and Sananbenesi, Farahnaz and Pang, Petti T. and Lu, Bai and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, n.i.h., extramural ;Nerve Degeneration;Animals;Synapses;Fear;Memory;Conditioning (Psychology);Neuronal Plasticity;Space Perception;Mice, Transgenic;Hippocampus;research support, n.i.h., intramural ;Association Learning;Time Factors;Dendrites;Learning;21 Neurophysiology;Maze Learning;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Anxiety;Cognition Disorders;Swimming}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {Harvard Medical School, Department of Pathology, Boston, Massachusetts 02115, USA.}, Pages = {825-38}, Pii = {S0896-6273(05)00951-7}, Pubmed = {16337919}, Title = {Opposing roles of transient and prolonged expression of p25 in synaptic plasticity and hippocampus-dependent memory}, Uuid = {7891483B-1EA8-4E32-B449-3094871B2734}, Volume = {48}, Year = {2005}, url = {papers/Fischer_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.10.033}} @article{Fishell:2005, Author = {Fishell, Gord and Kriegstein, Arnold}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {The Skirball Developmental Genetics Program and, Department of Cell Biology, New York University School of Medicine, 550 1st Avenue, New York, New York 10016, USA. fishell\@saturn.med.nyu.edu}, Pages = {361-2}, Pii = {S0896-6273(05)00352-1}, Pubmed = {15882631}, Title = {Cortical development: new concepts}, Uuid = {3278ABDA-A484-4942-86F5-186DBB1E5490}, Volume = {46}, Year = {2005}, url = {papers/Fishell_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.016}} @article{Fishell:2008, Abstract = {The precise stereotypic projections of pyramidal neurons within the six-layered cortex of mammals are key in allowing this structure to attain its high level of function. Recent studies have provided the first indications that postmitotic transcription factors are required for the formation and maintenance of both corticofugal and intracortical pyramidal cell populations. Here, we discuss these new findings in the context of our present understanding of cortical cell specification.}, Author = {Fishell, Gord and Hanashima, Carina}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Smilow Neuroscience Program, 5th Floor Smilow Research Building, New York University School of Medicine, 522 1st Avenue, New York, NY 10016, USA.}, Pages = {333-8}, Pii = {S0896-6273(08)00079-2}, Pubmed = {18255026}, Title = {Pyramidal neurons grow up and change their mind}, Uuid = {D971E3CE-525F-4098-8855-4BB8DAFD9825}, Volume = {57}, Year = {2008}, url = {papers/Fishell_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.01.018}} @article{Flames:2005, Abstract = {GABAergic interneurons are critical components of cortical circuits. However, understanding their function has become extremely challenging because they constitute one of the most diverse groups of cells in the central nervous system. Indeed, cortical GABAergic interneurons are heterogeneous in so many different ways--morphology, molecular profiling, electrical properties--that even attempts to discern what parameters should be used to identify cortical interneuron subtypes have failed to generate broad consensus among experts in the field. The extent to which cortical interneuron diversity emerges during development is largely unknown, but it is likely that insights on how this process takes place may help us understand their role as integrative and synchronizing elements in cortical function. Here, we review recent data on how the large variety of distinct classes of cortical interneurons may arise during development.}, Author = {Flames, Nuria and Mar{\'\i}n, Oscar}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Instituto de Neurociencias de Alicante, CSIC and Universidad Miguel Hern{\'a}ndez, Campus de San Juan, 03550 San Joan d'Alacant, Spain.}, Pages = {377-81}, Pii = {S0896-6273(05)00356-9}, Pubmed = {15882635}, Title = {Developmental mechanisms underlying the generation of cortical interneuron diversity}, Uuid = {997B3426-7D66-48E3-9559-ACD475A4BD63}, Volume = {46}, Year = {2005}, url = {papers/Flames_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.020}} @article{Flanary:2004, Abstract = {Normal somatic cells have a finite replicative capacity. With each cell division, telomeres shorten progressively until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell types in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. In this study, we show that telomere shortening accompanied by low to moderate telomerase activity, and ultimately senescence, occurs in rat microglia in vitro. When microglia are stimulated to divide with the mitogen granulocyte macrophage-colony stimulating factor (GM-CSF), longer telomeres are allowed to shorten, while shorter telomeres are lengthened. Telomerase activity is nearly 3-fold higher in GM-CSF-stimulated microglia initially, relative to unstimulated controls, and then declines to levels below those seen in controls before increasing again. Telomere attrition is also more rapid when microglia are grown in culture dishes of increasing size. Fluorescence in situ hybridization (FISH) analysis indicates that a nearly 3-fold variation in both inter- and intra-chromosomal telomere length exists in microglia. In contrast to microglia, cultured astrocytes exhibit a cyclical pattern of telomere lengthening and shortening over time, corresponding to a similar cycle of higher and lower telomerase activity. When astrocytes are passaged, mean telomere length increases initially from passage 1-2, remaining constant until passage 5, while the shortest telomeres are continually lengthened. In conclusion, the telomere shortening evident in microglia is accompanied by their progression to senescence by 32 days in vitro. In contrast, astrocytes, perhaps due to greater telomerase activity, have longer life spans and may be passaged repeatedly before entering senescence. Our findings provide an impetus to investigate the possibility that microglial telomere shortening may occur in vivo.}, Author = {Flanary, Barry E. and Streit, Wolfgang J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Rats;Comparative Study;Astrocytes;Not relevant;Cell Division;Telomere;11 Glia;Microglia;Colony-Stimulating Factors;Telomerase;Support, Non-U.S. Gov't;Cells, Cultured;Animals}, Month = {1}, Nlm_Id = {8806785}, Number = {1}, Organization = {Department of Neuroscience, University of Florida College of Medicine, McKnight Brain Institute, Gainesville, Florida 32610-0244, USA.}, Pages = {75-88}, Pubmed = {14648548}, Title = {Progressive telomere shortening occurs in cultured rat microglia, but not astrocytes}, Uuid = {1E30F4D9-C51A-4BC0-9410-99B608908626}, Volume = {45}, Year = {2004}, url = {papers/Flanary_Glia2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10301}} @article{Flanary:2003, Abstract = {Normal somatic cells have a finite replicative capacity. With each cell division, telomeres, the ends of linear chromosomes, progressively shorten until they reach a critical length, at which point the cells enter replicative senescence. Some cells maintain their telomeres by the action of the telomerase enzyme. Glia, particularly microglia, are the only adult cell type in the central nervous system (CNS) that exhibit a significant mitotic potential, and are thus susceptible to telomere shortening. Previous research in our laboratory has found that telomeres shorten in rat microglia with increasing time in vitro. Our current hypothesis is that telomeres shorten in rat brain in vivo with increasing age. Tissue samples of cerebellum and cortex were obtained from Sprague-Dawley rats of various ages. Genomic DNA and total protein was isolated from each sample for telomere length measurement via Southern blot analysis (up to 5 months) and telomerase activity measurement via TRAP analysis (up to 6 months), respectively. Telomere shortening occurs in vivo in both rat cerebellum and cortex from day 21 to approximately 5 months of age. Cortex samples possessed shorter telomeres than did cerebellum samples. The longest telomeres undergo the most dramatic shortening, while the shortest telomeres exhibit only slight attrition. Telomerase activity slowly increases from day 21 to approximately 6 months of age, with the cerebellum exhibiting higher activity than cortex in all instances. These results indicate that telomere shortening occurs in rat brain in vivo with increasing age, and that the low levels of telomerase activity present may be preferentially recruited to maintain the shortest telomeres while allowing the longer ones to shorten more rapidly. Since microglia are thought to be the only mature cells of the postnatal CNS undergoing appreciable cell division, we propose that the telomere shortening occurring in the adult rat brain with age can be largely attributed to microglial cell division. Our findings provide an impetus to further investigate the pattern of telomere length and telomerase activity that emerges with further aging in the rat brain.}, Author = {Flanary, Barry E. and Streit, Wolfgang J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1094-5458}, Journal = {J Anti Aging Med}, Keywords = {Aging;Rats, Sprague-Dawley;Rats;Not relevant;Telomere;Cerebellum;11 Glia;Support, Non-U.S. Gov't;Animals;Cerebral Cortex}, Nlm_Id = {9815684}, Number = {4}, Organization = {Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32610, USA.}, Pages = {299-308}, Pubmed = {15142431}, Title = {Telomeres shorten with age in rat cerebellum and cortex in vivo}, Uuid = {BC3D7885-6B86-43B0-A99E-2EA360D19B6E}, Volume = {6}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/109454503323028894}} @article{Flavell:2006, Abstract = {In the mammalian nervous system, neuronal activity regulates the strength and number of synapses formed. The genetic program that coordinates this process is poorly understood. We show that myocyte enhancer factor 2 (MEF2) transcription factors suppressed excitatory synapse number in a neuronal activity- and calcineurin-dependent manner as hippocampal neurons formed synapses. In response to increased neuronal activity, calcium influx into neurons induced the activation of the calcium/calmodulin-regulated phosphatase calcineurin, which dephosphorylated and activated MEF2. When activated, MEF2 promoted the transcription of a set of genes, including arc and synGAP, that restrict synapse number. These findings define an activity-dependent transcriptional program that may control synapse number during development.}, Author = {Flavell, Steven W. and Cowan, Christopher W. and Kim, Tae-Kyung K. and Greer, Paul L. and Lin, Yingxi and Paradis, Suzanne and Griffith, Eric C. and Hu, Linda S. and Chen, Chinfei and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Research Support, N.I.H., Extramural;GTPase-Activating Proteins;24 Pubmed search results 2008;Cytoskeletal Proteins;10 Development;Animals;Cells, Cultured;Transcription, Genetic;Myogenic Regulatory Factors;Rats, Long-Evans;Hippocampus;Synaptic Transmission;Transfection;Calcineurin;Synapses;Dendrites;Mutation;Gene Expression Regulation;21 Activity-development;Calcium;Rats;Oligonucleotide Array Sequence Analysis;Glutamic Acid;Recombinant Fusion Proteins;21 Neurophysiology;Research Support, Non-U.S. Gov't;Phosphorylation;Neurons;Nerve Tissue Proteins;RNA Interference;Excitatory Postsynaptic Potentials}, Month = {2}, Nlm_Id = {0404511}, Number = {5763}, Organization = {Neurobiology Program, Children's Hospital, and Departments of Neurology and Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {1008-12}, Pii = {311/5763/1008}, Pubmed = {16484497}, Title = {Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number}, Uuid = {4DC7499F-7DED-47EF-942D-9F58617829C9}, Volume = {311}, Year = {2006}, url = {papers/Flavell_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1122511}} @article{Flax:1998, Abstract = {Stable clones of neural stem cells (NSCs) have been isolated from the human fetal telencephalon. These self-renewing clones give rise to all fundamental neural lineages in vitro. Following transplantation into germinal zones of the newborn mouse brain they participate in aspects of normal development, including migration along established migratory pathways to disseminated central nervous system regions, differentiation into multiple developmentally and regionally appropriate cell types, and nondisruptive interspersion with host progenitors and their progeny. These human NSCs can be genetically engineered and are capable of expressing foreign transgenes in vivo. Supporting their gene therapy potential, secretory products from NSCs can correct a prototypical genetic metabolic defect in neurons and glia in vitro. The human NSCs can also replace specific deficient neuronal populations. Cryopreservable human NSCs may be propagated by both epigenetic and genetic means that are comparably safe and effective. By analogy to rodent NSCs, these observations may allow the development of NSC transplantation for a range of disorders. 1087-0156 Journal Article}, Author = {Flax, J. D. and Aurora, S. and Yang, C. and Simonin, C. and Wills, A. M. and Billinghurst, L. L. and Jendoubi, M. and Sidman, R. L. and Wolfe, J. H. and Kim, S. U. and Snyder, E. Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Nat Biotechnol}, Keywords = {Human;Stem Cells/cytology/physiology;Animals;Biotechnology;Cells, Cultured;10 Development;Transplantation, Heterologous;*Fetal Tissue Transplantation;*Stem Cell Transplantation;Cell Movement;Neurons/cytology/physiology/*transplantation;Genetic Engineering;Tay-Sachs Disease/enzymology/genetics/therapy;Animals, Newborn;Gene Therapy;Support, Non-U.S. Gov't;beta-N-Acetylhexosaminidase/deficiency/genetics;Support, U.S. Gov't, P.H.S.;Mice;*Brain Tissue Transplantation;Brain/cytology/growth &development/surgery;F}, Number = {11}, Organization = {Department of Neurology, Children's Hospital, Harvard Medical School, Boston, MA, USA.}, Pages = {1033-9}, Pubmed = {9831031}, Title = {Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes}, Uuid = {238E4693-3F74-4738-AEBC-3636CCBF6D14}, Volume = {16}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9831031}} @article{Fleck:2000, Abstract = {Human cortical heterotopia and neuronal migration disorders result in epilepsy; however, the precise mechanisms remain elusive. Here we demonstrate severe neuronal dysplasia and heterotopia throughout the granule cell and pyramidal cell layers of mice containing a heterozygous deletion of Lis1, a mouse model of human 17p13.3-linked lissencephaly. Birth-dating analysis using bromodeoxyuridine revealed that neurons in Lis1+/- murine hippocampus are born at the appropriate time but fail in migration to form a defined cell layer. Heterotopic pyramidal neurons in Lis1+/- mice were stunted and possessed fewer dendritic branches, whereas dentate granule cells were hypertrophic and formed spiny basilar dendrites from which the principal axon emerged. Both somatostatin- and parvalbumin-containing inhibitory neurons were heterotopic and displaced into both stratum radiatum and stratum lacunosum-moleculare. Mechanisms of synaptic transmission were severely disrupted, revealing hyperexcitability at Schaffer collateral-CA1 synapses and depression of mossy fiber-CA3 transmission. In addition, the dynamic range of frequency-dependent facilitation of Lis1+/- mossy fiber transmission was less than that of wild type. Consequently, Lis1+/- hippocampi are prone to interictal electrographic seizure activity in an elevated [K(+)](o) model of epilepsy. In Lis1+/- hippocampus, intense interictal bursting was observed on elevation of extracellular potassium to 6.5 mM, a condition that resulted in only minimal bursting in wild type. These anatomical and physiological hippocampal defects may provide a neuronal basis for seizures associated with lissencephaly.}, Author = {Fleck, M. W. and Hirotsune, S. and Gambello, M. J. and Phillips-Tansey, E. and Suares, G. and Mervis, R. F. and Wynshaw-Boris, A. and McBain, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;Golgi Apparatus;Animals;Microtubule-Associated Proteins;Humans;1-Alkyl-2-acetylglycerophosphocholine Esterase;Epilepsy;Cell Movement;Hippocampus;21 Dysplasia-heterotopia;Disease Models, Animal;Somatostatin;10 genetics malformation;Neurons;21 Neurophysiology;Parvalbumins;Nervous System Malformations;Mice;24 Pubmed search results 2008;Bromodeoxyuridine;Choristoma}, Month = {4}, Nlm_Id = {8102140}, Number = {7}, Organization = {Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.}, Pages = {2439-50}, Pubmed = {10729324}, Title = {Hippocampal abnormalities and enhanced excitability in a murine model of human lissencephaly}, Uuid = {7147A201-3A24-4282-8F92-C0B95C86EAAA}, Volume = {20}, Year = {2000}, url = {papers/Fleck_JNeurosci2000.pdf}} @article{Flint:1999, Abstract = {Oscillations in intracellular free calcium concentration ([Ca(2+)](i)) occur spontaneously in immature neurons of the developing cerebral cortex. Here, we show that developing murine cortical neurons exhibit calcium oscillations in response to direct activation of the mGluR5 subtype of the group I metabotropic glutamate receptor (mGluR). In contrast, other manipulations that elicit [Ca(2+)](i) increases produce simple, nonoscillatory changes. Furthermore, we find that spontaneous oscillatory [Ca(2+)](i) activity is blocked by antagonists of group I mGluRs, suggesting a specific role for mGluR activation in the promotion of oscillatory [Ca(2+)](i) dynamics in immature cortical neurons. The oscillatory pattern of [Ca(2+)](i) increases produced by mGluR activation might play a role in the regulation of gene expression and the control of developmental events.}, Author = {Flint, A. C. and Dammerman, R. S. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Animals;Lysine;Glutamic Acid;Neuroprotective Agents;Cycloleucine;Excitatory Amino Acid Agonists;Neocortex;Calcium;Microscopy, Fluorescence;Time Factors;Research Support, U.S. Gov't, P.H.S.;N-Methylaspartate;Neuroglia;21 Neurophysiology;Neurons;Protein Isoforms;Mice;24 Pubmed search results 2008;Receptors, Metabotropic Glutamate;Research Support, Non-U.S. Gov't}, Medline = {99449822}, Month = {10}, Nlm_Id = {7505876}, Number = {21}, Organization = {Center for Neurobiology, Columbia University, College of Physicians and Surgeons, New York, NY 10032, USA.}, Pages = {12144-9}, Pubmed = {10518590}, Title = {Endogenous activation of metabotropic glutamate receptors in neocortical development causes neuronal calcium oscillations}, Uuid = {605B3347-27DE-4F3B-A485-112871850C94}, Volume = {96}, Year = {1999}} @article{Floden:2007, Abstract = {In vitro culture of rodent microglia is a common system used to model proinflammatory changes in the brain. However, typical postnatal brain isolation protocols are time consuming and cell numbers acquired are often a rate-limiting factor for experimental progress. Large studies that rely on the use of primary microglia can, therefore, require excessive numbers of animals at considerable expense, additional technical support and culture incubator space. Although the addition of mitogens such as macrophage colony-stimulating factor, granulocyte macrophage-colony stimulating factor, and epidermal growth factor to the cultures can facilitate a higher yield, this adds additional expense and likely alters the microglial phenotype. We have defined a simple, inexpensive modification of our standard culture protocol that allows us to repetitively isolate microglia. In order to define a method for improving microglia yield, we utilized our standard mixed glial culture preparation derived from postnatal day 1-3 mouse brains. After isolating microglia from mixed cultures at 14 days in vitro, we added fresh media to the cultures for an additional 7 and 14 days to monitor microglial proliferation. We acquired a constant number of cells at each successive time point although the numbers were reduced from the first isolation. More importantly, in order to determine if our successive microglia isolates differed phenotypically we characterized several parameters of function. We compared their ability to secrete the proinflammatory cytokines interleukin-6 and tumor necrosis factor alpha after LPS stimulation. We also contrasted the phagocytic ability, morphology, and specific immunoreactivity (CD11b, CD68, CD45 and MHC II) of the culture ages. Our data demonstrate that microglia can be obtained from extended-time cultures provided periodic isolation is performed. Moreover, the cells retain a comparable in vitro phenotype. This demonstrates that cells from all ages can be combined for any given study. These findings are a viable and inexpensive way to increase and extend the microglial yield without increasing the number of animals used or adding costly mitogens. This method will be particularly useful for the preparation of microglia cultures from limited transgenic colonies.}, Author = {Floden, A. M. and Combs, C. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Animals;Cell Separation;Gene Expression Regulation;Cells, Cultured;Tumor Necrosis Factor-alpha;Phenotype;Brain;Microglia;Lipopolysaccharides;Antigens, CD;Cell Count;Mice, Inbred C57BL;11 Glia;Time Factors;Animals, Newborn;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Interleukin-6}, Month = {8}, Nlm_Id = {7905558}, Number = {2}, Organization = {Department of Pharmacology, Physiology & Therapeutics, University of North Dakota School of Medicine and Health Sciences, Neuroscience Building, 504 Hamline Street, Grand Forks, ND 58202-9037, United States.}, Pages = {218-24}, Pii = {S0165-0270(07)00207-5}, Pubmed = {17553568}, Title = {Microglia repetitively isolated from in vitro mixed glial cultures retain their initial phenotype}, Uuid = {86B54A08-BE99-4358-ADB1-A9D519D88A3F}, Volume = {164}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2007.04.018}} @article{Florkiewicz:1984, Abstract = {A stable cell line expressing a complementary DNA clone encoding the vesicular stomatitis virus glycoprotein fused and formed polykaryons at pH 5.5. The formation of polykaryons was dependent on the presence of glycoprotein anchored at the cell surface and could be prevented by incubation of cells with a monoclonal antibody to the glycoprotein. Fusion occurred at a pH 0.5 unit lower than that observed for cells infected with vesicular stomatitis virus.}, Author = {Florkiewicz, R. Z. and Rose, J. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Cell Membrane;Membrane Glycoproteins;Cell Fusion;Antibodies, Monoclonal;Research Support, U.S. Gov't, P.H.S.;Cell Line;Viral Proteins;Vesicular stomatitis-Indiana virus;Glycoproteins;15 Retrovirus mechanism;Animals;Hydrogen-Ion Concentration;Mice;Viral Envelope Proteins;24 Pubmed search results 2008}, Medline = {84274419}, Month = {8}, Nlm_Id = {0404511}, Number = {4663}, Pages = {721-3}, Pubmed = {6087454}, Title = {A cell line expressing vesicular stomatitis virus glycoprotein fuses at low pH}, Uuid = {249DF706-EE2C-11DA-8605-000D9346EC2A}, Volume = {225}, Year = {1984}} @article{Flugel:1999, Abstract = {Microglia and brain macrophages represent a substantial fraction of the cells present in astrocytic gliomas. Yet, the functional role of microglia in these tumors has remained enigmatic. We have compared rat microglial cells and thymocytes with regard to their ability to present purified CNS proteins, MBP and S100beta, as well as C6 glioma cells to specific T lymphocytes. In addition, a new cytotoxicity assay based on fluorescence activated cell sorting of tumor cells carrying the green fluorescent protein was established. This assay was used to determine the influence of microglial population density and activational state on C6 glioma cell survival in vitro. Microglia were consistently found to present MBP and S100beta less efficiently than thymocytes and appeared to be unable to present C6 glioma cells to cytotoxic T lymphocytes. In addition, high concentrations of microglial cells attenuated the cytotoxic effects of these T cells on C6 glioma cells whereas thymocytes significantly supported their specific killing. It is suggested that defense functions of microglial cells against C6 glioma are severely compromised and that the observed deficiency in antigen presentation may play an important role for astrocytoma growth in vivo.}, Author = {Fl{\"u}gel, A. and Labeur, M. S. and Grasbon-Frodl, E. M. and Kreutzberg, G. W. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0736-5748}, Journal = {Int J Dev Neurosci}, Keywords = {Antigens, Neoplasm;Flow Cytometry;Tumor Cells, Cultured;Luminescent Proteins;Glioma;Rats;T-Lymphocytes, Cytotoxic;Animals, Genetically Modified;Thymus Gland;11 Glia;Microglia;Antigen-Presenting Cells;Brain Neoplasms;Green Fluorescent Proteins;Animals;Cells, Cultured;Cell Separation}, Medline = {20036194}, Nlm_Id = {8401784}, Number = {5-6}, Organization = {Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.}, Pages = {547-56}, Pubmed = {10571416}, Title = {Microglia only weakly present glioma antigen to cytotoxic T cells}, Uuid = {E4D20645-9E41-4FD4-9094-8155D4F69AAF}, Volume = {17}, Year = {1999}} @article{Flugel:2001, Abstract = {Direct injury of the brain is followed by inflammatory responses regulated by cytokines and chemoattractants secreted from resident glia and invading cells of the peripheral immune system. In contrast, after remote lesion of the central nervous system, exemplified here by peripheral transection or crush of the facial and hypoglossal nerve, the locally observed inflammatory activation is most likely triggered by the damaged cells themselves, that is, the injured neurons. The authors investigated the expression of the chemoattractants monocyte chemoattractant protein MCP-1, regulation on activation normal T-cell expressed and secreted (RANTES), and interferon-gamma inducible protein IP10 after peripheral nerve lesion of the facial and hypoglossal nuclei. In situ hybridization and immunohistochemistry revealed an induction of neuronal MCP-1 expression within 6 hours postoperation, reaching a peak at 3 days and remaining up-regulated for up to 6 weeks. MCP-1 expression was almost exclusively confined to neurons but was also present on a few scattered glial cells. The authors found no alterations in the level of expression and cellular distribution of RANTES or IP10, which were both confined to neurons. Protein expression of the MCP-1 receptor CCR2 did not change. MCP-1, expressed by astrocytes and activated microglia, has been shown to be crucial for monocytic, or T-cell chemoattraction, or both. Accordingly, expression of MCP-1 by neurons and its corresponding receptor in microglia suggests that this chemokine is involved in neuron and microglia interaction.}, Author = {Fl{\"u}gel, A. and Hager, G. and Horvat, A. and Spitzer, C. and Singer, G. M. and Graeber, M. B. and Kreutzberg, G. W. and Schwaiger, F. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0271-678X}, Journal = {J Cereb Blood Flow Metab}, Keywords = {Receptors, Cytokine;Microtubule-Associated Proteins;Animals;Gene Expression Regulation;Rats;Brain;Rats, Wistar;11 Glia;RNA, Messenger;Male;In Situ Hybridization;Neurons;RANTES;Axotomy;Laterality;Immunohistochemistry;Monocyte Chemoattractant Protein-1;Facial Nerve;Hypoglossal Nerve;Research Support, Non-U.S. Gov't}, Medline = {21024390}, Month = {1}, Nlm_Id = {8112566}, Number = {1}, Organization = {Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.}, Pages = {69-76}, Pubmed = {11149670}, Title = {Neuronal MCP-1 expression in response to remote nerve injury}, Uuid = {239DA0B5-EA6B-4C76-BFB6-777DAEF163A5}, Volume = {21}, Year = {2001}} @article{Flugel:2001a, Abstract = {Macrophages in the brain can have a triple source. They may originate from recently blood-derived precursors, from the largely resident perivascular cell population (perivascular macrophages and related cells), and from intrinsic parenchymal as well as perivascular microglia. Although continuous exchange of part of the perivascular cell population with bone marrow-derived precursors is now accepted, the turnover of adult parenchymal microglia has remained enigmatic. Using bone-marrow chimeras carrying an unexpressed marker gene and carbon labeling of peripheral monocyte/macrophages in a combined model of facial nerve axotomy and transfer experimental autoimmune encephalitis, we demonstrate for the first time that there is an easy to induce exchange between parenchymal central nervous system (CNS) microglia and the macrophage precursor cell pool of the bone marrow. Furthermore, very low level infiltration of the CNS parenchyma by recently bone marrow-derived microglia could be observed after simple peripheral nerve axotomy that is followed by neuronal regeneration. Thus, microglial cells can be considered wanderers between the peripheral immune system and the CNS where they may act as a "Trojan horse" in infections. The fact that recently bone marrow-derived parenchymal microglia fully integrate into a regenerating brain nucleus' architecture encourages entirely new approaches for delivering genes into the adult CNS.}, Author = {Fl{\"u}gel, A. and Bradl, M. and Kreutzberg, G. W. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Transgenes;Cell Differentiation;Multiple Sclerosis;Rats, Inbred Lew;Monocytes;Macrophages;Chimera;Rats;Thymidine Kinase;Animals;Microglia;11 Glia;Immunophenotyping;Nerve Regeneration;In Situ Hybridization;Bone Marrow Cells;Cell Lineage;Gene Therapy;Encephalomyelitis, Autoimmune, Experimental;Axotomy;Simplexvirus;Biological Markers;Facial Nerve;Research Support, Non-U.S. Gov't}, Medline = {21482213}, Month = {10}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Neuroimmunology, Max-Planck-Institute of Neurobiology, Martinsried, Germany.}, Pages = {74-82}, Pii = {10.1002/jnr.1198}, Pubmed = {11599003}, Title = {Transformation of donor-derived bone marrow precursors into host microglia during autoimmune CNS inflammation and during the retrograde response to axotomy}, Uuid = {EE80116F-5DC4-47A4-80CC-86BA7088D759}, Volume = {66}, Year = {2001}} @article{Foffani:2007, Abstract = {Ripples are sharp-wave-associated field oscillations (100-300 Hz) recorded in the hippocampus during behavioral immobility and slow-wave sleep. In epileptic rats and humans, a different and faster oscillation (200-600 Hz), termed fast ripples, has been described. However, the basic mechanisms are unknown. Here, we propose that fast ripples emerge from a disorganized ripple pattern caused by unreliable firing in the epileptic hippocampus. Enhanced synaptic activity is responsible for the irregular bursting of CA3 pyramidal cells due to large membrane potential fluctuations. Lower field interactions and a reduced spike-timing reliability concur with decreased spatial synchronization and the emergence of fast ripples. Reducing synaptically driven membrane potential fluctuations improves both spike-timing reliability and spatial synchronization and restores ripples in the epileptic hippocampus. Conversely, a lower spike-timing reliability, with reduced potassium currents, is associated with ripple shuffling in normal hippocampus. Therefore, fast ripples may reflect a pathological desynchronization of the normal ripple pattern.}, Author = {Foffani, Guglielmo and Uzcategui, Yoryani G. and Gal, Beatriz and Menendez de la Prida, Liset}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Pilocarpine;Electrophysiology;Animals;Rats;Muscarinic Agonists;Epilepsy;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Lithium Carbonate;research support, non-u.s. gov't;Male;21 Neurophysiology;Neurons;Membrane Potentials;Delayed Rectifier Potassium Channels;24 Pubmed search results 2008;Fourier Analysis;Immunohistochemistry;Data Interpretation, Statistical}, Month = {9}, Nlm_Id = {8809320}, Number = {6}, Organization = {Fundaci{\'o}n del Hospital Nacional de Parapl{\'e}jicos para la Investigaci{\'o}n y la Integraci{\'o}n, SESCAM, Toledo 45071, Spain.}, Pages = {930-41}, Pii = {S0896-6273(07)00587-9}, Pubmed = {17880896}, Title = {Reduced spike-timing reliability correlates with the emergence of fast ripples in the rat epileptic hippocampus}, Uuid = {7EE68563-8D46-4C32-8B80-DC2DFC45AFEC}, Volume = {55}, Year = {2007}, url = {papers/Foffani_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.07.040}} @article{Fontanini:2006, Abstract = {Over the past few years, it has become clear that oscillatory dynamics of cortical networks are closely involved in sensory coding, attention, memory and sleep. Although most experimental and theoretical studies have focused on the neocortex, we believe that progress in understanding cortical oscillations can be advanced by also considering the olfactory system--which shares many basic properties with the neocortex and shows similar oscillatory patterns. Besides offering the advantage of a greater experimental tractability, the olfactory cortex might prove to be instrumental in uncovering general functional principles of neocortical oscillations, by virtue of the potentially important role of olfaction during neocortical evolution. In this article, we illustrate how such an evolution-based comparative approach can provide novel insights into neocortical slow-wave sleep oscillations and their relationship to respiration.}, Author = {Fontanini, Alfredo and Bower, James M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Electroencephalography;Olfactory Pathways;Biological Clocks;21 Neurophysiology;Neocortex;Brain Mapping;Nerve Net;Animals;Humans;24 Pubmed search results 2008;review}, Month = {8}, Nlm_Id = {7808616}, Number = {8}, Organization = {Volen National Center for Complex Systems and Department of Psychology, MS 013, Brandeis University, Waltham, MA 02493, USA. alfredof\@brandeis.edu}, Pages = {429-37}, Pii = {S0166-2236(06)00142-1}, Pubmed = {16842864}, Title = {Slow-waves in the olfactory system: an olfactory perspective on cortical rhythms}, Uuid = {CDDFFB56-A88E-43E7-BCF5-5A297DA45851}, Volume = {29}, Year = {2006}, url = {papers/Fontanini_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.06.013}} @article{Fordyce:2005, Abstract = {Many CNS disorders involve an inflammatory response that is orchestrated by cells of the innate immune system: macrophages, neutrophils, and microglia (the endogenous CNS immune cell). Hence, there is considerable interest in anti-inflammatory strategies that target these cells. Microglia express Kv1.3 (KCNA3) channels, which we showed previously are important for their proliferation and the NADPH-mediated respiratory burst. Here, we demonstrate the potential for targeting Kv1.3 channels to control CNS inflammation. Rat microglia express Kv1.2, Kv1.3, and Kv1.5 transcripts and protein, but only a Kv1.3 current was detected. When microglia were activated with lipopolysaccharide or a phorbol ester, only the Kv1.3 transcript (but not protein) expression changed. Using a Transwell cell-culture system that allows separate drug treatment of microglia or neurons, we found that activated microglia killed postnatal hippocampal neurons through a process that requires Kv1.3 channel activity in microglia but not in neurons. A major neurotoxic molecule in this model was peroxynitrite, which is formed from superoxide and nitric oxide; thus, it is significant that Kv1.3 channel blockers reduced the respiratory burst, but not nitric oxide production, by the activated microglia. In addressing the biochemical pathway affected by Kv1.3 channel activity, we found that Kv1.3 acts via a different cellular mechanism from the broad-spectrum drug minocycline, which is often used in animal models of neuroinflammation. That is, the dose-dependent reduction in neuron killing by minocycline corresponded with a reduction in p38 mitogen-activated protein kinase activation in microglia; however, none of the Kv1.3 blockers affected p38 activation.}, Author = {Fordyce, Christopher B. and Jagasia, Ravi and Zhu, Xiaoping and Schlichter, Lyanne C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {07 Excitotoxicity Apoptosis;Alpha;11 Glia}, Month = {8}, Nlm_Id = {8102140}, Number = {31}, Organization = {Division of Cellular and Molecular Biology, Toronto Western Research Institute, University Health Network, Toronto, Ontario, M5T 2S8, Canada.}, Pages = {7139-49}, Pii = {25/31/7139}, Pubmed = {16079396}, Title = {Microglia Kv1.3 channels contribute to their ability to kill neurons}, Uuid = {2D7ACEB2-BBAB-4C96-9F19-5FF427A2E23C}, Volume = {25}, Year = {2005}, url = {papers/Fordyce_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1251-05.2005}} @article{Forni:2006, Abstract = {Hydrocephalus is a common and variegated pathology often emerging in newborn children after genotoxic insults during pregnancy (Hicks and D'Amato, 1980). Cre recombinase is known to have possible toxic effects that can compromise normal cell cycle and survival. Here we show, by using three independent nestin Cre transgenic lines, that high levels of Cre recombinase expression into the nucleus of neuronal progenitors can compromise normal brain development. The transgenics analyzed are the nestin Cre Balancer (Bal1) line, expressing the Cre recombinase with a nuclear localization signal, and two nestin CreER(T2) (Cre recombinase fused with a truncated estrogen receptor) mice lines with different levels of expression of a hybrid CreER(T2) recombinase that translocates into the nucleus after tamoxifen treatment. All homozygous Bal1 nestin Cre embryos displayed reduced neuronal proliferation, increased aneuploidy and cell death, as well as defects in ependymal lining and lamination of the cortex, leading to microencephaly and to a form of communicating hydrocephalus. An essentially overlapping phenotype was observed in the two nestin CreER(T2) transgenic lines after tamoxifen mediated-CreER(T2) translocation into the nucleus. Neither tamoxifen-treated wild-type nor nestin CreER(T2) oil-treated control mice displayed these defects. These results indicate that some forms of hydrocephalus may derive from a defect in neuronal precursors proliferation. Furthermore, they underscore the potential risks for developmental studies of high levels of nuclear Cre in neurogenic cells.}, Author = {Forni, Paolo E. and Scuoppo, Claudio and Imayoshi, Itaru and Taulli, Riccardo and Dastr\`{u}, Walter and Sala, Valentina and Betz, Ulrich A. K. and Muzzi, Patrizia and Martinuzzi, Daniela and Vercelli, Alessandro E. and Kageyama, Ryoichiro and Ponzetto, Carola}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Animals;Gene Expression Regulation, Developmental;Selective Estrogen Receptor Modulators;Brain;Integrases;Hydrocephalus;Receptors, Estrogen;21 Dysplasia-heterotopia;Mice, Transgenic;Cell Proliferation;Microcephaly;23 Technique;Aneuploidy;Nuclear Localization Signals;Nervous System Malformations;21 Neurophysiology;Intermediate Filament Proteins;Neurons;Ependyma;Tamoxifen;Mice;24 Pubmed search results 2008;Biological Markers;Cell Death;Nerve Tissue Proteins;Stem Cells}, Month = {9}, Nlm_Id = {8102140}, Number = {37}, Organization = {Department of Anatomy, Pharmacology, and Forensic Medicine, University of Turin, 10126 Turin, Italy. paolo.forni\@unito.it}, Pages = {9593-602}, Pii = {26/37/9593}, Pubmed = {16971543}, Title = {High levels of Cre expression in neuronal progenitors cause defects in brain development leading to microencephaly and hydrocephaly}, Uuid = {59FB2871-68E4-468C-B492-A314FFE82130}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2815-06.2006}} @article{Foster:2006, Abstract = {The hippocampus has long been known to be involved in spatial navigational learning in rodents, and in memory for events in rodents, primates and humans. A unifying property of both navigation and event memory is a requirement for dealing with temporally sequenced information. Reactivation of temporally sequenced memories for previous behavioural experiences has been reported in sleep in rats. Here we report that sequential replay occurs in the rat hippocampus during awake periods immediately after spatial experience. This replay has a unique form, in which recent episodes of spatial experience are replayed in a temporally reversed order. This replay is suggestive of a role in the evaluation of event sequences in the manner of reinforcement learning models. We propose that such replay might constitute a general mechanism of learning and memory.}, Author = {Foster, David J. and Wilson, Matthew A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {research support, n.i.h., extramural ;21 Neurophysiology;Wakefulness;Action Potentials;Models, Neurological;Hippocampus;Rest;Space Perception;Memory;Running;Rats;Behavior;Electrophysiology;Animals;Learning;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {0410462}, Number = {7084}, Organization = {Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 46-5223, Cambridge, Massachusetts 02139, USA. djfoster\@mit.edu}, Pages = {680-3}, Pii = {nature04587}, Pubmed = {16474382}, Title = {Reverse replay of behavioural sequences in hippocampal place cells during the awake state}, Uuid = {3121AFF9-D65E-48E4-B786-4EDB7F16274D}, Volume = {440}, Year = {2006}, url = {papers/Foster_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04587}} @article{Fouad:2005, Abstract = {Numerous obstacles to successful regeneration of injured axons in the adult mammalian spinal cord exist. Consequently, a treatment strategy inducing axonal regeneration and significant functional recovery after spinal cord injury has to overcome these obstacles. The current study attempted to address multiple impediments to regeneration by using a combinatory strategy after complete spinal cord transection in adult rats: (1) to reduce inhibitory cues in the glial scar (chondroitinase ABC), (2) to provide a growth-supportive substrate for axonal regeneration [Schwann cells (SCs)], and (3) to enable regenerated axons to exit the bridge to re-enter the spinal cord (olfactory ensheathing glia). The combination of SC bridge, olfactory ensheathing glia, and chondroitinase ABC provided significant benefit compared with grafts only or the untreated group. Significant improvements were observed in the Basso, Beattie, and Bresnahan score and in forelimb/hindlimb coupling. This recovery was accompanied by increased numbers of both myelinated axons in the SC bridge and serotonergic fibers that grew through the bridge and into the caudal spinal cord. Although prominent descending tracts such as the corticospinal and reticulospinal tracts did not successfully regenerate through the bridge, it appeared that other populations of regenerated fibers were the driving force for the observed recovery; there was a significant correlation between numbers of myelinated fibers in the bridge and improved coupling of forelimb and hindlimb as well as open-field locomotion. Our study tests how proven experimental treatments interact in a well-established animal model, thus providing needed direction for the development of future combinatory treatment regimens.}, Author = {Fouad, Karim and Schnell, Lisa and Bunge, Mary B. and Schwab, Martin E. and Liebscher, Thomas and Pearse, Damien D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia}, Month = {2}, Nlm_Id = {8102140}, Number = {5}, Organization = {University of Alberta, Faculty of Rehabilitation Medicine, Edmonton, Canada T6G 2G4. karim.fouad\@ualberta.ca}, Pages = {1169-78}, Pii = {25/5/1169}, Pubmed = {15689553}, Title = {Combining Schwann cell bridges and olfactory-ensheathing glia grafts with chondroitinase promotes locomotor recovery after complete transection of the spinal cord}, Uuid = {1F1A6936-8500-449E-8DB1-8D28F5562C95}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3562-04.2005}} @article{Fowler:2002, Abstract = {In the mammalian brain, adult neurogenesis has been found to occur primarily in the subventricular zone (SVZ) and dentate gyrus of the hippocampus (DG) and to be influenced by both exogenous and endogenous factors. In the present study, we examined the effects of male exposure or social isolation on neurogenesis in adult female prairie voles (Microtus ochrogaster). Newly proliferated cells labeled by a cell proliferation marker, 5-bromo-2'-deoxyuridine (BrdU), were found in the SVZ and DG, as well as in other brain areas, such as the amygdala, hypothalamus, neocortex, and caudate/putamen. Two days of male exposure significantly increased the number of BrdU-labeled cells in the amygdala and hypothalamus in comparison to social isolation. Three weeks later, group differences in BrdU labeling generally persisted in the amygdala, whereas in the hypothalamus, the male-exposed animals had more BrdU-labeled cells than did the female-exposed animals. In the SVZ, 2 days of social isolation increased the number of BrdU-labeled cells compared to female exposure, but this difference was no longer present 3 weeks later. We have also found that the vast majority of the BrdU-labeled cells contained a neuronal marker, indicating neuronal phenotypes. Finally, group differences in the number of cells undergoing apoptosis were subtle and did not seem to account for the observed differences in BrdU labeling. Together, our data indicate that social environment affects neuron proliferation in a stimulus- and site- specific manner in adult female prairie voles.}, Author = {Fowler, C. D. and Liu, Y. and Ouimet, C. and Wang, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:35:09 -0400}, Journal = {J Neurobiol}, Keywords = {B pdf;02 Adult neurogenesis migration}, Number = {2}, Organization = {Department of Psychology and Program of Neuroscience, Florida State University, Tallahassee, Florida 32306.}, Pages = {115-28.}, Title = {The effects of social environment on adult neurogenesis in the female prairie vole}, Uuid = {151E41B7-11F9-4662-B800-070C658211C6}, Volume = {51}, Year = {2002}, url = {papers/Fowler_JNeurobiol2002.pdf}} @article{Fox:1998, Abstract = {Long-range, directed migration is particularly dramatic in the cerebral cortex, where postmitotic neurons generated deep in the brain migrate to form layers with distinct form and function. In the X-linked dominant human disorder periventricular heterotopia (PH), many neurons fail to migrate and persist as nodules lining the ventricular surface. Females with PH present with epilepsy and other signs, including patent ductus arteriosus and coagulopathy, while hemizygous males die embryonically. We have identified the PH gene as filamin 1 (FLN1), which encodes an actin-cross-linking phosphoprotein that transduces ligand-receptor binding into actin reorganization, and which is required for locomotion of many cell types. FLN1 shows previously unrecognized, high-level expression in the developing cortex, is required for neuronal migration to the cortex, and is essential for embryogenesis.}, Author = {Fox, J. W. and Lamperti, E. D. and Ekiolu, Y. Z. and Hong, S. E. and Feng, Y. and Graham, D. A. and Scheffer, I. E. and Dobyns, W. B. and Hirsch, B. A. and Radtke, R. A. and Berkovic, S. F. and Huttenlocher, P. R. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:45 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cerebral Ventricles;Epilepsy;Fetal Death;24 Pubmed search results 2008;Microfilament Proteins;Male;Contractile Proteins;Brain Diseases;Cerebral Cortex;Sex Characteristics;Animals;Brain;Research Support, U.S. Gov't, P.H.S.;Gene Expression Regulation, Developmental;Phenotype;X Chromosome;Magnetic Resonance Imaging;Chromosome Mapping;21 Epilepsy;Abnormalities, Multiple;Aging;Pedigree;Female;21 Neurophysiology;Mice;Research Support, Non-U.S. Gov't;Neurons;Humans;Choristoma;Embryonic and Fetal Development}, Medline = {99098194}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.}, Pages = {1315-25}, Pii = {S0896-6273(00)80651-0}, Pubmed = {9883725}, Title = {Mutations in filamin 1 prevent migration of cerebral cortical neurons in human periventricular heterotopia}, Uuid = {0E99B0A5-1E09-450C-9E36-AFD3AF9FF4A3}, Volume = {21}, Year = {1998}, url = {papers/Fox_Neuron1998.pdf}} @article{Fox:2007, Abstract = {The resting brain is not silent, but exhibits organized fluctuations in neuronal activity even in the absence of tasks or stimuli. This intrinsic brain activity persists during task performance and contributes to variability in evoked brain responses. What is unknown is if this intrinsic activity also contributes to variability in behavior. In the current fMRI study, we identify a relationship between human brain activity in the left somatomotor cortex and spontaneous trial-to-trial variability in button press force. We then demonstrate that 74\%of this brain-behavior relationship is attributable to ongoing fluctuations in intrinsic activity similar to those observed during resting fixation. In addition to establishing a functional and behavioral significance of intrinsic brain activity, these results lend new insight into the origins of variability in human behavior.}, Author = {Fox, Michael D. and Snyder, Abraham Z. and Vincent, Justin L. and Raichle, Marcus E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {21 Neurophysiology;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Radiology, Washington University, St Louis, MO 63110, USA. foxm\@npg.wustl.edu}, Pages = {171-84}, Pii = {S0896-6273(07)00666-6}, Pubmed = {17920023}, Title = {Intrinsic fluctuations within cortical systems account for intertrial variability in human behavior}, Uuid = {C751ECC3-FE59-46EC-A786-89469F2DF9FD}, Volume = {56}, Year = {2007}, url = {papers/Fox_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.08.023}} @article{Fox:1996, Abstract = {The segregation of thalamocortical inputs into eye-specific stripes in the developing cat or monkey visual cortex is prevented by manipulations that perturb or abolish neural activity in the visual pathway. Such findings show that proper development of the functional organization of visual cortex is dependent on normal patterns of neural activity. The generalisation of this conclusion to other sensory cortices has been questioned by findings that the segregation of thalamocortical afferents into a somatotopic barrel pattern in developing rodent primary somatosensory cortex (S1) is not prevented by activity blockade. We show that a temporary block of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in rat S1 during the critical period for barrel development disrupts the topographic refinement of thalamocortical connectivity and columnar organization. These effects are evident well after the blockade is ineffective and thus may be permanent. Our findings show that neural activity and specifically the activation of postsynaptic cortical neurons has a prominent role in establishing the primary sensory map in S1, as well as the topographic organization of higher order synaptic connections.}, Author = {Fox, K. and Schlaggar, B. L. and Glazewski, S. and O'Leary, D. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Excitatory Amino Acid Antagonists;Receptors, Glutamate;Animals;Synapses;Aging;Rats;Afferent Pathways;research support, u.s. gov't, p.h.s. ;2-Amino-5-phosphonovalerate;Rats, Sprague-Dawley;comparative study ;Reference Values;Vibrissae;Animals, Newborn;Thalamus;Haplorhini;Cerebral Cortex;21 Neurophysiology;Neurons;Somatosensory Cortex;21 Activity-development;24 Pubmed search results 2008;Cats;Visual Cortex}, Month = {5}, Nlm_Id = {7505876}, Number = {11}, Organization = {Department of Physiology, University of Minnesota, Minneapolis 55455, USA.}, Pages = {5584-9}, Pubmed = {8643619}, Title = {Glutamate receptor blockade at cortical synapses disrupts development of thalamocortical and columnar organization in somatosensory cortex}, Uuid = {628D3576-32EC-4F10-BB07-7117AB502515}, Volume = {93}, Year = {1996}} @article{Fox:2002, Abstract = {1095-9203 Comment Journal Article}, Author = {Fox, K. and Caterson, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {Science}, Keywords = {G;Human;Dendrites/physiology;Animals;*Neuronal Plasticity;Rats;Proteochondroitin Sulfates/*metabolism;Visual Cortex/*physiology;Extracellular Matrix/*metabolism/physiology;Synapses/physiology;11 Glia;Vision;Extracellular Matrix Proteins/metabolism;Astrocytes/physiology/transplantation;Chondroitin ABC Lyase/*metabolism;Hyaluronic Acid;Dominance, Ocular;Neurites/physiology}, Number = {5596}, Organization = {Neuroscience Research Group and the Connective Tissue Biology Labs, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, UK. foxkd\@cardiff.ac.uk}, Pages = {1187-9}, Title = {Neuroscience. Freeing the bain from the perineuronal net}, Uuid = {78108B0B-1345-4553-A186-3B17512F0467}, Volume = {298}, Year = {2002}, url = {papers/Fox_Science2002.pdf}} @article{Forster:2002, Abstract = {The mammary glands of prepubertal estrogen receptor (ER)beta-- mice are morphologically indistinguishable from those of WT littermates. It appears that, although ERbeta is expressed in the mouse mammary gland, it is not involved in ductal growth of the gland. In this study, we examined the possibility that ERbeta has a role in the differentiated function of the mammary gland. Pregnancy is rare in ERbeta-- mice, but an intensive breeding program produced seven pregnant ERbeta-- mice, of which five did not eat their offspring and continued to successful lactation. Histomorphological comparison of lactating glands revealed that alveoli were larger and there was less secretory epithelium in ERbeta-- than in WT mice. Ultrastructural analysis showed abundant milk droplets and normal apical villi in the luminal epithelial cells, but the extracellular matrix and lamina basalis were reduced, and very frequently the interepithelial cell space was increased. Levels of the adhesion molecules, E-cadherin, connexin 32, occludin, and integrin alpha2 were reduced, and no zona occludens was detectable. In addition, there was widespread expression of the proliferation marker, Ki-67, in luminal epithelial cells in ERbeta-- but not in WT mice. These findings suggest a role for ERbeta in organization and adhesion of epithelial cells and hence for differentiated tissue morphology. We speculate that, because a reduced risk for breast cancer is conferred on women who breast-feed at an early age, ERbeta could contribute to this risk reduction by facilitating terminal differentiation of the mammary gland.}, Author = {F{\"o}rster, Carola and M{\"a}kela, Sari and W{\"a}rri, Anni and Kietz, Silke and Becker, David and Hultenby, Kjell and Warner, Margaret and Gustafsson, Jan-Ake A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {10 Development;Cell Differentiation;Animals;10 Hippocampus;Pregnancy;Mammary Glands, Animal;Tight Junctions;Epithelial Cells;Lactation;Female;Receptors, Estrogen;Cell Polarity;Fertility;Gap Junctions;Integrin alpha6;Integrin alpha2;Cadherins;Mice, Knockout;Estrogen Receptor beta;Mice;Research Support, Non-U.S. Gov't}, Medline = {22342748}, Month = {11}, Nlm_Id = {7505876}, Number = {24}, Organization = {Department of Medical Nutrition, Karolinska Institute, Novum, S-141 86 Huddinge, Sweden.}, Pages = {15578-83}, Pii = {192561299}, Pubmed = {12438700}, Title = {Involvement of estrogen receptor beta in terminal differentiation of mammary gland epithelium}, Uuid = {BF311DFC-72AB-4126-A3B7-03AA185587AB}, Volume = {99}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.192561299}} @article{Forster:2002a, Abstract = {The extracellular matrix molecule Reelin is required for the correct positioning of neurons during the development of the forebrain. However, the mechanism of Reelin action on neuronal migration is poorly understood. Reelin is assumed to act on neurons directly, but it may also affect the differentiation of glial cells necessary for neuronal migration. Here we show that a regular glial scaffold fails to form in vivo in the dentate gyrus of mice deficient of Reelin or Disabled 1, a neuronal adaptor protein in the Reelin signaling pathway. A subset of these defects is observed in mice that lack beta(1)-class integrins, known to bind Reelin. Moreover, recombinant Reelin induced branching of glial processes in vitro. Our data suggest that Reelin affects glial differentiation via Disabled 1 and beta(1)-class integrin-dependent signaling pathways.}, Author = {F{\"o}rster, Eckart and Tielsch, Albrecht and Saum, Barbara and Weiss, Karl Heinz and Johanssen, Celine and Graus-Porta, Diana and M{\"u}ller, Ulrich and Frotscher, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Glial Fibrillary Acidic Protein;Golgi Apparatus;Signal Transduction;Animals;Humans;Mutation;Hippocampus;Serine Endopeptidases;Cell Adhesion Molecules, Neuronal;RNA, Messenger;Prosencephalon;In Situ Hybridization;Extracellular Matrix Proteins;Cell Line;Animals, Newborn;Antigens, CD29;Neuroglia;DNA, Complementary;Mice;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {22247732}, Month = {10}, Nlm_Id = {7505876}, Number = {20}, Organization = {Anatomisches Institut, Universit{\"a}t Freiburg, P.O. Box 111, D-79001 Freiburg, Germany. foerster\@uni-feiburg.de}, Pages = {13178-83}, Pii = {202035899}, Pubmed = {12244214}, Title = {Reelin, Disabled 1, and beta 1 integrins are required for the formation of the radial glial scaffold in the hippocampus}, Uuid = {59B7EE44-C34B-11DA-969D-000D9346EC2A}, Volume = {99}, Year = {2002}, url = {papers/Förster_ProcNatlAcadSciUSA2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.202035899}} @article{Frade:2000, Abstract = {During their early postmitotic life, a proportion of the nascent retinal ganglion cells (RGCs) are induced to die as a result of the interaction of nerve growth factor (NGF) with the neurotrophin receptor p75. To analyse the mechanisms by which NGF promotes apoptosis, an in vitro culture system consisting of dissociated E5 retinal cells was established. In this system, NGF-induced apoptosis was only observed in the presence of insulin and neurotrophin-3, conditions that favour the birth of RGCs and other neurones expressing the glycoprotein G4. The pro-apoptotic effect of NGF on the G4-positive neurones was evident after 10 hours in vitro and was preceded by a significant upregulation of cyclin B2, but not cyclin D1, and the presence of mitotic nuclei in these cells. Brain-derived neurotrophic factor prevented both the increase of cyclin B2 expression in the G4-positive neurones and the NGF-induced cell death. Finally, pharmacologically blocking cell-cycle progression using the cyclin-dependent kinase inhibitor roscovitine prevented NGF-induced cell death in a dose-dependent manner. These results strongly suggest that the apoptotic signalling initiated by NGF requires a driving stimulus manifested by the neuronal birth and is preceded by the unscheduled re-entry of postmitotic neurones into the cell cycle. 0021-9533 Journal Article}, Author = {Frade, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Journal = {J Cell Sci}, Keywords = {Animals;Brain-Derived Neurotrophic Factor/physiology;Cells, Cultured;Purines/pharmacology;Neurons/cytology/*physiology;Insulin/physiology;EE pdf;Culture Media, Conditioned;08 Aberrant cell cycle;Retina/cytology/*embryology;Support, Non-U.S. Gov't;Chick Embryo;Cell Death/drug effects/physiology;Apoptosis/drug effects/physiology;Cell Cycle/*physiology;Growth Inhibitors/pharmacology;Neurotrophin 3/physiology;Cell Differentiation/physiology;Nerve Growth Factor/antagonists &inhibitors/*physiology}, Organization = {Instituto Cajal de Neurobiologia, CSIC, Avenida Doctor Arce 37, Madrid E28002, Spain. isrf303\@fresno.csic.es.}, Pages = {1139-48}, Pubmed = {10704365}, Title = {Unscheduled re-entry into the cell cycle induced by NGF precedes cell death in nascent retinal neurones}, Uuid = {4813D1CA-F1B2-4F96-AB25-4D667BD935A8}, Volume = {113 ( Pt 7)}, Year = {2000}, url = {papers/Frade_JCellSci2000.pdf}} @article{Franceschini:2004, Abstract = {Polysialic acid (PSA) on NCAM is an important modulator of cell-cell interactions during development and regeneration. Here we investigated whether PSA overexpression influences neural cell migration and myelination. We stably expressed a GFP-tagged polysialytransferase, PSTGFP, in mouse neurospheres and induced prolonged PSA synthesis. Using a chick xenograft assay for migration, we show that PSA can instruct precursor migration along the ventral pathway. PSA persistence did not change neural precursor multipotentiality in vitro but induced a delay in oligodendrocyte differentiation. PSTGFP+ precursors showed widespread engraftment in shiverer brain, closely similar to that observed with control precursors expressing a fluorescent protein. Initially, myelination by oligodendrocytes was delayed but, eventually, down-regulation of PSTGFP occurred, allowing myelination to proceed. Thus down-regulation of polysialyltransferases takes place even in cells where its RNA is under the control of a heterologous promoter and engineering PSA overexpression in neural precursors does not cause irreversible unphysiological effects.}, Author = {Franceschini, Isabelle and Vitry, Sandrine and Padilla, Fran\c{c}oise and Casanova, Philippe and Tham, To Nam and Fukuda, Minoru and Rougon, Genevi\`{e}ve and Durbec, Pascale and Dubois-Dalcq, Monique}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {Animals;Gene Expression Regulation;Cells, Cultured;Humans;Comparative Study;Cell Movement;Mice, Transgenic;Nerve Fibers, Myelinated;Mice, Inbred C57BL;Research Support, U.S. Gov't, P.H.S.;Sialic Acids;Chick Embryo;3T3 Cells;Neurons;Mice;Protein Engineering;24 Pubmed search results 2008;Neural Cell Adhesion Molecule L1;Stem Cells;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {9100095}, Number = {2}, Organization = {Unit{\'e} de Neurovirologie et R{\'e}g{\'e}n{\'e}ration du Syst\`{e}me Nerveux, Institut Pasteur, 75724 Paris cedex 15, France.}, Pages = {151-62}, Pii = {S1044-7431(04)00127-7}, Pubmed = {15485771}, Title = {Migrating and myelinating potential of neural precursors engineered to overexpress PSA-NCAM}, Uuid = {779B993B-A63D-4899-9CA5-C2C814245E14}, Volume = {27}, Year = {2004}, url = {papers/Franceschini_MolCellNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2004.05.006}} @article{Franchi:2000, Abstract = {This study examined the ability of adult rat motor cortex to reorganize its relationship with the somatic musculature following the severing and regeneration of a motor nerve. For this purpose experiments were performed on ten male albino rats where the facial nerve on one side was severed, sutured and allowed to regenerate for 6 months. Cortical motor output organization was assessed by mapping the vibrissal movement area extension and thresholds evoked by intracortical electrical stimulation in anesthetized rats. In all ten animals, the cortical output pattern of the motor cortex contralateral to the normal side was compared with that contralateral to the reinnervated side. After facial nerve reinnervation, the most notable differences in primary motor cortex (M1) output organization in the hemispheres contralateral to the reinnervated side were: (a) the area from which vibrissa movements could be evoked at low thresholds was smaller (mean 1.2+/-0.38 mm, range 0.75-1.75 mm), decreasing to 64.2\%below those in hemispheres contralateral to the normal side (mean 3.4+/-0.52 mm, range 2.5-4 mm). The reorganized vibrissa area consisted of contiguous or discontinuous points shrunken to the medialmost portion of normal M1 vibrissal representation. (b) There was a clear medial extension of the forelimb representation, and a more modest lateral expansion of eye representation, into the vibrissa territory. The mean threshold required to evoke vibrissa movements was significantly higher in the hemispheres contralateral to the reinnervated side than in the other hemispheres (normal 23.9+/-9.7 microA vs reinnervated 37.8+/-11.9 microA; P< or =0.0001; t-test). The stimulation currents required to evoke other types of body movements were similar in the normal and reinnervated sides. Similar results were observed in all rats. In conclusion, these results indicate that motor nerve reinnervation is sufficient to produce long-lasting changes at a higher motor cortical level. This supports the notion that central supranuclear mechanisms may also be involved in the disorder of facial movements observed after facial nerve reinnervation.}, Author = {Franchi, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Movement;Animals;Rats;Neuronal Plasticity;Face;Denervation;Forelimb;Vibrissae;Rats, Inbred Strains;Motor Cortex;Male;Nerve Regeneration;Eye Movements;Electromyography;Sensory Thresholds;Laterality;Hindlimb;24 Pubmed search results 2008;Facial Nerve;Brain Mapping}, Medline = {20220919}, Month = {3}, Nlm_Id = {0043312}, Number = {1}, Organization = {Dipartimento di Scienze Biomediche e Terapie Avanzate, Universit\`{a} di Ferrara, Italy. fhg\@dns.unife.it}, Pages = {33-43}, Pubmed = {10759169}, Title = {Reorganization of vibrissal motor representation following severing and repair of the facial nerve in adult rats}, Uuid = {0E62F53F-F591-478C-ABD8-67F8F644934F}, Volume = {131}, Year = {2000}} @article{Francione:1994, Abstract = {Magnetic resonance imaging allows the identification of heterotopic gray matter (HGM) in medically intractable partial epilepsies. The relationships between HGM and the epileptogenic zone remain, however, unclear. In a case of a temporo-parietal epilepsy studied by stereo-EEG, interictal and ictal electrical activity of a temporal HGM were recorded, showing: (1) an intralesional electrical activity, (2) the possible presence of asynchronous spikes, and (3) an early but never initial, or isolated, involvement during ictal discharges. This suggests that the presurgical and surgical management of HGM must be guided, as for other lesions, by the coherence existing between ictal clinical and electrical features, and anatomical data.}, Author = {Francione, S. and Kahane, P. and Tassi, L. and Hoffmann, D. and Durisotti, C. and Pasquier, B. and Munari, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0013-4694}, Journal = {Electroencephalogr Clin Neurophysiol}, Keywords = {Prognosis;Epilepsies, Partial;Electroencephalography;10 Development;Magnetic Resonance Imaging;Adult;Female;Choristoma;10 genetics malformation;Humans;Brain;Temporal Lobe;24 Pubmed search results 2008;case reports}, Month = {4}, Nlm_Id = {0375035}, Number = {4}, Organization = {Department of Neurosciences, CHU Grenoble, France.}, Pages = {284-90}, Pubmed = {7512909}, Title = {Stereo-EEG of interictal and ictal electrical activity of a histologically proved heterotopic gray matter associated with partial epilepsy}, Uuid = {22F3CDA9-ABAF-4E68-959F-41040DA34451}, Volume = {90}, Year = {1994}} @article{Francis:2006, Abstract = {Epilepsy and mental retardation, originally of unknown cause, are now known to result from many defects including cortical malformations, neuronal circuitry disorders and perturbations of neuronal communication and synapse function. Genetic approaches in combination with MRI and related imaging techniques continually allow a re-evaluation and better classification of these disorders. Here we review our current understanding of some of the primary defects involved, with insight from recent molecular biology advances, the study of mouse models and the results of neuropathology analyses. Through these studies the molecular determinants involved in the control of neuron number, neuronal migration, generation of cortical laminations and convolutions, integrity of the basement membrane at the pial surface, and the establishment of neuronal circuitry are being elucidated. We have attempted to integrate these results with the available data concerning, in particular, human brain development, and to emphasize the limitations in some cases of extrapolating from rodent models. Taking such species differences into account is clearly critical for understanding the pathophysiological mechanisms associated with these disorders.}, Author = {Francis, Fiona and Meyer, Gundela and Fallet-Bianco, Catherine and Moreno, Sarah and Kappeler, Caroline and Socorro, Alfredo Cabrera and Tuy, Fran\c{c}oise Phan Dinh and Beldjord, Cherif and Chelly, Jamel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:21 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Animals;Humans;21 Epilepsy;review;Mutation;History, 20th Century;historical article;History, 16th Century;History, 21st Century;Cell Proliferation;Brain Diseases;History, Ancient;research support, non-u.s. gov't ;History, 17th Century;Cell Movement;Cerebral Cortex;21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8918110}, Number = {4}, Organization = {Institut Cochin, D{\'e}partement de G{\'e}n{\'e}tique et D{\'e}veloppement, Paris, F-75014 France. francis\@cochin.inserm.fr}, Pages = {877-93}, Pii = {EJN4649}, Pubmed = {16519653}, Title = {Human disorders of cortical development: from past to present}, Uuid = {89424AD1-005D-4F5D-BD06-991A0BFB085D}, Volume = {23}, Year = {2006}, url = {papers/Francis_EurJNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.04649.x}} @article{Francis:1999, Abstract = {Recently, we and others reported that the doublecortin gene is responsible for X-linked lissencephaly and subcortical laminar heterotopia. Here, we show that Doublecortin is expressed in the brain throughout the period of corticogenesis in migrating and differentiating neurons. Immunohistochemical studies show its localization in the soma and leading processes of tangentially migrating neurons, and a strong axonal labeling is observed in differentiating neurons. In cultured neurons, Doublecortin expression is highest in the distal parts of developing processes. We demonstrate by sedimentation and microscopy studies that Doublecortin is associated with microtubules (MTs) and postulate that it is a novel MAP. Our data suggest that the cortical dysgeneses associated with the loss of Doublecortin function might result from abnormal cytoskeletal dynamics in neuronal cell development.}, Author = {Francis, F. and Koulakoff, A. and Boucher, D. and Chafey, P. and Schaar, B. and Vinet, M. C. and Friocourt, G. and McDonnell, N. and Reiner, O. and Kahn, A. and McConnell, S. K. and Berwald-Netter, Y. and Denoulet, P. and Chelly, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Neuron}, Keywords = {RNA, Messenger/biosynthesis;10 Development;Rats, Long-Evans;Cells, Cultured;Rats;Animal;Cytoskeleton/metabolism/ultrastructure;Microtubule-Associated Proteins/biosynthesis/*physiology;In Situ Hybridization;Support, Non-U.S. Gov't;Antibody Specificity;Neurons/metabolism/*physiology/ultrastructure;Brain/cytology/embryology/metabolism;Support, U.S. Gov't, P.H.S.;Tubulin/isolation &purification/metabolism;Mice;Cell Differentiation/physiology;Immunohistochemistry;Neuropeptides/biosynthesis/*physiology;Cell Movement/physiology;Phosphoproteins/biosynthesis/*physiology;F}, Number = {2}, Organization = {U129 de l'INSERM, Institut Cochin de Genetique Moleculaire, Paris. ffrancis\@infobiogen.fr}, Pages = {247-56.}, Title = {Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons}, Uuid = {9AD7D46C-6D0F-11DA-A4FE-000D9346EC2A}, Volume = {23}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10399932}} @article{Frank:1996, Abstract = {Rat optic nerves were subjected to crush injury to study the local tissue reactions leading to wound healing and tissue repair. We used antibodies against glial fibrillary acidic protein (GFAP), vimentin, the S1OO protein (S1OOP), lysozyme, and ED1 as markers for astroglial cells and microglia/macrophages at the light and electron microscopic level during the 3 weeks following the crush. The crush injury produced a vast area of tissue damage including the disruption of the blood-brain barrier (BBB). In the first days after crushing, astrocytes were absent from the lesion site. S1OOP-positive astrocytes reappeared in the lesion center as early as 6 days after crushing. These astrocytes reestablished former topological structures such as perivascular and subpial glia limitans. At the edges of the lesion site reactive astrocytes enclosed and embedded axonal and myelin debris. Preceding the astroglial repopulation, a massive infiltration of microglia/macrophages (phagocytes) into the lesion center took place. ED1-positive/lysozyme- positive cells of round shape were seen in the lesion center at 2 days after crushing, and their number peaked around 1 week after crushing. They efficiently cleared the debris from the lesion site and mostly disappeared after 3 weeks. With immuno-electron microscopy we found the ED1 antigen related to the membranes of phagosomes. The microglia/macrophages observed in the nerve segments distal of the lesion (Wallerian degeneration site) were different from those in the lesion center: 1) they appeared later, about 6 days after crushing; 2) they were ED1 positive, but lysozyme negative and showed a branched morphology; and 3) they persisted in the distal nerve segment but showed little phagocytosis. We suggest that these cells are mostly activated microglia.}, Author = {Frank, M. and Wolburg, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Animals;Astrocytes;Macrophages;Rats;Microglia;Cell Count;Optic Nerve;Rats, Wistar;Not relevant;11 Glia;Time Factors;Male;Support, Non-U.S. Gov't;Nerve Crush;Immunohistochemistry;Microscopy, Electron;Biological Markers;Optic Nerve Injuries}, Medline = {96430043}, Month = {3}, Nlm_Id = {8806785}, Number = {3}, Organization = {Universitat Tubingen, Institut fur Pathologie, Germany.}, Pages = {227-40}, Pii = {10.1002/(SICI)1098-1136(199603)16:3<227::AID-GLIA5>3.0.CO;2-Z}, Pubmed = {8833193}, Title = {Cellular reactions at the lesion site after crushing of the rat optic nerve}, Uuid = {2FFB7CB9-821C-4426-B9B7-9FCCB1821FA9}, Volume = {16}, Year = {1996}} @article{Frank:2001, Abstract = {During a critical period of brain development, occluding the vision of one eye causes a rapid remodeling of the visual cortex and its inputs. Sleep has been linked to other processes thought to depend on synaptic remodeling, but a role for sleep in this form of cortical plasticity has not been demonstrated. We found that sleep enhanced the effects of a preceding period of monocular deprivation on visual cortical responses, but wakefulness in complete darkness did not do so. The enhancement of plasticity by sleep was at least as great as that produced by an equal amount of additional deprivation. These findings demonstrate that sleep and sleep loss modify experience-dependent cortical plasticity in vivo. They suggest that sleep in early life may play a crucial role in brain development.}, Author = {Frank, M. G. and Issa, N. P. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Wakefulness;Animals;Sleep, REM;Neuronal Plasticity;Blindness;Visual Pathways;Female;Male;Sleep;Action Potentials;research support, u.s. gov't, p.h.s.;Neurons;21 Neurophysiology;21 Cortical oscillations;24 Pubmed search results 2008;Visual Cortex;Electroencephalography;Cats}, Month = {4}, Nlm_Id = {8809320}, Number = {1}, Organization = {W. M. Keck Foundation Center, for Integrative Neuroscience, Department of Physiology, University of California, San Francisco, San Francisco, CA 94143-0444, USA.}, Pages = {275-87}, Pii = {S0896-6273(01)00279-3}, Pubmed = {11343661}, Title = {Sleep enhances plasticity in the developing visual cortex}, Uuid = {D044E070-9077-42BE-8622-B8F092A837FB}, Volume = {30}, Year = {2001}, url = {papers/Frank_Neuron2001.pdf}} @article{Frankshten:1986, Abstract = {Influence of cerebral hypoxia and hyperventilatory hypocapnia on the ECoG and focal epileptiform activity of the cerebral cortex induced with local application of strychnine was studied in cats with transection of spinal cord at C1. Although both hypoxia and hypocapnia produced synchronization of the cerebral cortex electrical activity, i.e. exerted the same effects on the ECoG, their influence on cortical excitability was quite different: hypoxia suppressed the epileptiform activity whereas hypocapnia facilitated it.}, Author = {Frankshten, S. I. and Smolin, L. N. and Sergeeva, L. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0015-329X}, Journal = {Fiziol Zh SSSR Im I M Sechenova}, Keywords = {Epilepsy;21 Epilepsy;Electroencephalography;24 Pubmed search results 2008;21 Neurophysiology;Cats;English Abstract;Strychnine;Animals;Hypoxia, Brain;Decerebrate State;Cerebral Cortex;Carbon Dioxide}, Medline = {86248217}, Month = {5}, Nlm_Id = {0427673}, Number = {5}, Pages = {576-9}, Pubmed = {3087794}, Title = {[Effect of cerebral hypoxia and hyperventilation hypocapnia on the epileptiform activity of the cerebral cortex of the cat]}, Uuid = {DE725F61-1204-44F2-963B-C8ACC3BFC952}, Volume = {72}, Year = {1986}} @article{Fransson:2007, Abstract = {In the absence of any overt task performance, it has been shown that spontaneous, intrinsic brain activity is expressed as systemwide, resting-state networks in the adult brain. However, the route to adult patterns of resting-state activity through neuronal development in the human brain is currently unknown. Therefore, we used functional MRI to map patterns of resting-state activity in infants during sleep. We found five unique resting-states networks in the infant brain that encompassed the primary visual cortex, bilateral sensorimotor areas, bilateral auditory cortex, a network including the precuneus area, lateral parietal cortex, and the cerebellum as well as an anterior network that incorporated the medial and dorsolateral prefrontal cortex. These results suggest that resting-state networks driven by spontaneous signal fluctuations are present already in the infant brain. The potential link between the emergence of behavior and patterns of resting-state activity in the infant brain is discussed.}, Author = {Fransson, and Ski{\"o}ld, and Horsch, and Nordell, and Blennow, and Lagercrantz, and Aden,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2014-09-22 21:00:19 +0000}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {21 Neurophysiology; human; infant; fmri; connectivity; default mode network; mirror symmetry; neuron}, Month = {9}, Nlm_Id = {7505876}, Number = {39}, Organization = {Magnetic Resonance Research Center, Department of Clinical Neuroscience, Stockholm Brain Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden; Neonatal Research Unit, Astrid Lindgren Children's Hospital, Karolinska Institute, SE-171 76 Stockholm, Sweden;}, Pages = {15531--15536}, Pii = {0704380104}, Pubmed = {17878310}, Title = {Resting-state networks in the infant brain}, Uuid = {733337C2-D658-43A8-BB5F-F702AC5F85C2}, Volume = {104}, Year = {2007}, url = {papers/Fransson_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0704380104}} @article{Frantseva:2002, Abstract = {Traumatic brain injury results in neuronal loss and associated neurological deficits. Although most research on the factors leading to trauma-induced damage focuses on synaptic or ionic mechanisms, the possible role of direct intercellular communication via gap junctions has remained unexplored. Gap junctions connect directly the cytoplasms of coupled cells; hence, they offer a way to propagate stress signals from cell to cell. We investigated the contribution of gap junctional communication (GJC) to cell death using an in vitro trauma model. The impact injury, induced by a weight dropped on the distal CA1 area of organotypic hippocampal slices, results in glutamate-dependent cell loss. The gap junctional blockers carbenoxolone and octanol decreased significantly post-traumatic cell death, measured by propidium iodide staining over a 72 hr period after the impact. Dye coupling in the pyramidal layers was enhanced immediately after the injury and decreased over the following 24 hr. To determine whether specific connexins were involved in the spread of trauma-induced cell death, we used organotypic slices from connexin43 (Cx43) knock-out mice, as well as acute knock-outs by incubation with antisense oligodeoxynucleotides. Simultaneous knockdown of two neuronal connexins resulted in significant neuroprotection. Slices from the null-mutant Cx43 mice, as well as the acute Cx43 knockdown, also showed decreased cell death after the impact. The gap junctional blockers alleviated the trauma- induced impairment of synaptic function as measured by electrophysiological field potential recordings. These results indicate that GJC enhances the cellular vulnerability to traumatic injury. Hence, specific gap junctions could be a novel target to reduce injury and secondary damage to the brain and maximize recovery from trauma.}, Author = {Frantseva, M. V. and Kokarovtseva, L. and Naus, C. G. and Carlen, P. L. and MacFabe, D. and Perez Velazquez, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurosci}, Keywords = {07 Excitotoxicity Apoptosis;E}, Number = {3}, Organization = {The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.}, Pages = {644-53.}, Title = {Specific gap junctions enhance the neuronal vulnerability to brain traumatic injury}, Uuid = {8A0A16F0-61D2-48D1-9256-A344B1426C32}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11826094%20http://www.jneurosci.org/cgi/content/full/22/3/644%20http://www.jneurosci.org/cgi/content/abstract/22/3/644}} @article{Frantz:1996, Abstract = {Early in development, neural progenitors in cerebral cortex normally produce neurons of several layers during successive cell divisions. The laminar fate of their daughters depends on environmental cues encountered just before mitosis. At the close of neurogenesis, however, cortical progenitors normally produce neurons destined only for the upper layers. To assess the developmental potential of these cells, upper-layer progenitors were transplanted into the cerebral cortex of younger hosts, in which deep-layer neurons were being generated. These studies reveal that late cortical progenitors are not competent to generate deep-layer neurons and are instead restricted to producing the upper layers.}, Author = {Frantz, G. D. and McConnell, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Research Support, Non-U.S. Gov't;Cell Line;Stem Cells;Research Support, U.S. Gov't, P.H.S.;Ferrets;Mitosis;Animals;Cell Movement;Cerebral Cortex;Neurons;Stem Cell Transplantation}, Medline = {96310877}, Month = {7}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Biological Sciences, Stanford University, California 94305, USA.}, Pages = {55-61}, Pubmed = {8755478}, Title = {Restriction of late cerebral cortical progenitors to an upper-layer fate}, Uuid = {5215BB39-AFA2-4689-A713-2535E5A584BE}, Volume = {17}, Year = {1996}} @article{Frappe:2001, Abstract = {In a previous study we provided evidence that embryonic (E) day 16 frontal cortical cells grafted into the occipital cortex of newborn rats receive inputs from the ventrolateral (VL) and ventromedial (VM) thalamic nuclei which, normally, project to the frontal cortex (25). The present study was designed to examine further the conditions of development of the thalamic innervation of heterotopic neocortical grafts. We demonstrate that VL/VM axons do not provide transitory aberrant input to the occipital cortex either in intact newborn animals or in rats having received neonatal occipital lesion and subsequent graft of E16 occipital cells. These findings indicate, therefore, that the VL/VM projection to the graft does not result from the stabilization of an initial widespread cortical projection from these thalamic nuclei occurring either spontaneously or in response to the lesion and homotopic transplantation procedures. We also show that the VL/VM projection to frontal-to-occipital grafts develops within a few days posttransplantation and is maintained in adulthood. Finally, this study establishes that most VL/VM axons which enter the grafts are not collaterals of thalamofrontal axons. After having reached the cortex, they proceed caudally primarily within the infragranular layers. The findings of this and previous (25) in vivo studies for the first time provide evidence that developing thalamic axons have the capacity to respond to signals from grafts of E16 cortical cells and are capable of deviating their trajectory to establish contact with the grafts. Only those axons arising from thalamic nuclei appropriate for the cortical locus of origin of the grafted cells respond to the guidance signals. The mechanisms by which the thalamic axons find their way to the graft probably rely on cell-contact signaling and/or long-range attraction exerted by diffusible molecules.}, Author = {Frapp{\'e}, I. and Gaillard, A. and Roger, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Fluorescent Dyes;Animals;Frontal Lobe;Thalamic Nuclei;Brain Tissue Transplantation;Rats;Neural Pathways;Neocortex;Female;Axons;Rats, Wistar;Fetal Tissue Transplantation;Male;Axonal Transport;Animals, Newborn;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Occipital Lobe;24 Pubmed search results 2008;Nerve Fibers;Gestational Age}, Medline = {21257866}, Month = {6}, Nlm_Id = {0370712}, Number = {2}, Organization = {D{\'e}partement des Neurosciences, CNRS, UMR 6558, Universit{\'e} de Poitiers, 86022 Poitiers Cedex, France.}, Pages = {264-75}, Pii = {S0014488601976691}, Pubmed = {11358441}, Title = {Attraction exerted in vivo by grafts of embryonic neocortex on developing thalamic axons}, Uuid = {D85F533A-F8D2-49B6-ADA7-920B1B7B641B}, Volume = {169}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.2001.7669}} @article{Frappe:1999, Abstract = {A number of molecular and hodological experiments have provided evidence that there is an early commitment of neocortical neurons to express features unique to a certain cortical area. However, the findings of several transplantation experiments have indicated that late embryonic cortical tissue heterotopically grafted into the neocortex of newborn rats receives a set of thalamic projections appropriate for the host cortical locus within which it develops. To provide further information on the extent to which neocortical neurons are predetermined to develop area-specific systems of connections, in this study we have compared the pattern of thalamic afferents to grafts of embryonic day 16 occipital or frontal neocortex transplanted into the occipital cortex of newborn rats. Two months after grafting, a retrograde neurotracer (cholera toxin, subunit b) was injected into the grafts to precisely assess the number of cells in the visual- and/or motor-related nuclei of the host thalamus projecting to each category of transplants (occipital-to-occipital or frontal-to-occipital). Transplants of embryonic occipital cortex received significant input from several visual-related thalamic nuclei, i.e. the lateral posterior and lateral dorsal nuclei, and no input from motor-related thalamic nuclei. However, only few labeled cells were found in the dorsal lateral geniculate nucleus, which was systematically affected by a severe atrophy, probably in response to the lesion of the occipital cortex performed prior to the transplantation. By comparison, transplants of frontal origin received a substantial input from the ventrolateral and ventromedial thalamic nuclei, which normally project to the frontal cortex, but received a weak input from the lateral posterior and lateral dorsal nuclei. Neocortical neurons grafted heterotopically into the neocortex of newborn hosts are not only able to contact cortical and subcortical targets appropriate for their embryonic site of origin, but are also susceptible to derive thalamic inputs closely related to their embryonic origin.}, Author = {Frapp{\'e}, I. and Roger, M. and Gaillard, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {24 Pubmed search results 2008;Thalamic Nuclei;Rats;Female;Rats, Wistar;Atrophy;Occipital Lobe;Animals, Newborn;Synaptic Transmission;Transplantation, Heterotopic;Thalamus;Male;Animals;Fetal Tissue Transplantation;Frontal Lobe}, Medline = {99174941}, Month = {3}, Nlm_Id = {7605074}, Number = {2}, Organization = {UMR 6558, D{\'e}partement des Neurosciences, Laboratoire de Neurophysiologie, Facult{\'e} des Sciences, Universit{\'e} de Poitiers, France.}, Pages = {409-21}, Pii = {S0306452298003790}, Pubmed = {10077323}, Title = {Transplants of fetal frontal cortex grafted into the occipital cortex of newborn rats receive a substantial thalamic input from nuclei normally projecting to the frontal cortex}, Uuid = {2F70812F-022F-46C8-B615-FF37D9313DA3}, Volume = {89}, Year = {1999}} @article{Fraser:1995, Abstract = {The ability to determine the functional capacity of putative human hematopoietic stem cell (HSC) populations requires in vivo assays in which long-term multilineage differentiation can be assessed. We hypothesized that if human fetal bone was transplanted adjacent to a fetal thymus fragment in severe combined immunodeficient (SCID) mice, a conjoint organ might form in which HSC in the human bone marrow (BM) would mimic human multilineage differentiation into progenitor cells, B cells, and myeloid cells; undergo self-renewal; and migrate to and differentiate into T cells within the thymic microenvironment. To test this possibility, SCID mice were transplanted subcutaneously with HLA class I mismatched fetal bone, thymus, and spleen fragments (SCID-hu BTS). We found that the BM of SCID-hu BTS grafts maintained B cells, myeloid cells, CD34+ cells for at least 36 weeks posttransplant. Assayable hematopoietic progenitors colony-forming units-granulocyte-macrophage were present in 100\%(66/66) of grafts over a period of 28 weeks. Cells with a HSC phenotype (CD34+Thy-1+Lin-) were maintained for 20 weeks in SCID-hu BTS grafts. These CD34+Thy-1+Lin- cells had potent secondary multilineage reconstituting potential when isolated and injected into a secondary HLA mismatched SCID-hu bone assay and analyzed 8 weeks later. In addition, early progenitors within the BM of SCID-hu BTS grafts were capable of migrating to the human thymus and undergoing differentiation through immature CD4+CD8+ double-positive T cells and produce mature T cells with a CD4+CD8- or CD8+CD4- phenotype that could be detected for at least 36 weeks. Phenotypically defined human fetal liver (FL) and umbilical cord blood (UCB) hematopoietic stem cell populations were injected into irradiated SCID-hu BTS grafts to assess their multilineage repopulating capacity and to assess the ability of the BTS system to provide an environment where multiple lineages might differentiate from a common stem cell pool. Injection of irradiated grafts with FL HSC or UCB HSC cells resulted in donor-derived B cells, myeloid cells, immature and mature T cells, and CD34+ cells in individual grafts when analyzed 8 weeks postreconstitution, further showing the multipotential nature of these stem cell populations. In addition, a strong correlation was observed between maintenance of host graft-derived CD8+ cells and failure of donor stem cell engraftment.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Fraser, C. C. and Kaneshima, H. and Hansteen, G. and Kilpatrick, M. and Hoffman, R. and Chen, B. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Cell Differentiation;Animals;Humans;Transplantation, Heterologous;Lymphocytes;Bone Transplantation;Antigens, CD;Mice, SCID;Kinetics;11 Glia;Fetal Tissue Transplantation;Hematopoietic Stem Cell Transplantation;Bone Marrow Cells;Transplantation, Homologous;Flow Cytometry;Hematopoietic Stem Cells;Mice;HLA Antigens}, Medline = {95383636}, Month = {9}, Nlm_Id = {7603509}, Number = {5}, Organization = {Experimental Cell Therapy Group, SyStemix Inc, Palo Alto, CA 94304, USA.}, Pages = {1680-93}, Pubmed = {7655000}, Title = {Human allogeneic stem cell maintenance and differentiation in a long-term multilineage SCID-hu graft}, Uuid = {F764731F-B01D-4A2A-AB8B-7236CD92238B}, Volume = {86}, Year = {1995}} @article{Freed:1987, Abstract = {The murine leukemia virus envelope protein is synthesized as a precursor molecule, Pr85env, which is proteolytically cleaved at an arginine residue to produce two mature envelope proteins, gp70 and p15(E). The results presented here indicate that mutation to lysine of the arginine found at the envelope precursor cleavage site results in a precursor which is cleaved with an efficiency at least 10-fold lower than the efficiency with which the wild-type protein is cleaved. This mutation has been used to investigate the requirement for envelope protein processing in various aspects of retroviral infection. Viruses produced by cells transfected with mutant proviral clones are approximately 10-fold less infectious than wild-type viruses. Mutant viruses are incapable of inducing XC cell syncytium formation and are 100-fold less efficient than wild-type viruses at rendering cells resistant to superinfection. Envelope glycoproteins bearing the lysine mutation are found in reduced amounts on the surface of infected cells, and as a result mutant virions contain significantly less envelope protein than do wild-type virions. The phenotypic effects of the processing mutation described here are most likely the result of this paucity of envelope glycoproteins in virions carrying the mutation.}, Author = {Freed, E. O. and Risser, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Mice, Inbred AKR;Transfection;Mutation;Cell Fusion;Cell Membrane;Mice, Inbred BALB C;24 Pubmed search results 2008;Glycosylation;Research Support, U.S. Gov't, P.H.S.;Glycoproteins;15 Retrovirus mechanism;Animals;Cells, Cultured;Leukemia Virus, Murine;Viral Envelope Proteins;Mice}, Medline = {87284162}, Month = {9}, Nlm_Id = {0113724}, Number = {9}, Pages = {2852-6}, Pubmed = {3039173}, Title = {The role of envelope glycoprotein processing in murine leukemia virus infection}, Uuid = {0206842C-4327-11DB-A5D2-000D9346EC2A}, Volume = {61}, Year = {1987}} @article{Freeman:2006, Abstract = {Glial cells are not passive spectators during nervous system assembly, rather they are active participants that exert significant control over neuronal development. Well-established roles for glia in shaping the developing nervous system include providing trophic support to neurons, modulating axon pathfinding, and driving nerve fasciculation. Exciting recent studies have revealed additional ways in which glial cells also modulate neurodevelopment. Glial cells regulate the number of neurons at early developmental stages by dynamically influencing neural precursor divisions, and at later stages by promoting neuronal cell death through engulfment. Glia also participate in the fine sculpting of neuronal connections by pruning excess axonal projections, shaping dendritic spines, and secreting multiple factors that promote synapse formation and functional maturation. These recent insights provide further compelling evidence that glial cells, through their diverse cellular actions, are essential contributors to the construction of a functionally mature nervous system.}, Author = {Freeman, Marc R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {review;Synapses;Neuroglia;Research Support, Non-U.S. Gov't;Dendrites;Stem Cells;Cell Death;Nervous System;Animals;24 Pubmed search results 2008;Neurons;Axons}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01605-2324, USA. Marc.Freeman\@umassmed.edu}, Pages = {119-25}, Pii = {S0959-4388(05)00186-8}, Pubmed = {16387489}, Title = {Sculpting the nervous system: glial control of neuronal development}, Uuid = {901FC932-DBE7-425A-8085-D1C7EBA7551F}, Volume = {16}, Year = {2006}, url = {papers/Freeman_CurrOpinNeurobiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.12.004}} @article{Frenkel:2004, Abstract = {We used a chronic recording method to document the kinetics of ocular dominance (OD) plasticity induced by temporary lid closure in young mice. We find that monocular deprivation (MD) induces two separate modifications: (1) rapid, deprivation-induced response depression and (2) delayed, deprivation-enabled, experience-dependent response potentiation. To gain insight into how altering retinal activity triggers these cortical responses, we compared the effects of MD by lid closure with monocular inactivation (MI) by intravitreal injection of tetrodotoxin. We find that MI fails to induce deprived-eye response depression but promotes potentiation of responses driven by the normal eye. These effects of MI in juvenile mice closely resemble the effects of MD in adult mice. Understanding how MI and MD differentially affect activity in the visual system of young mice may provide key insight into how the critical period ends.}, Author = {Frenkel, Mikhail Y. and Bear, Mark F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Vision, Monocular;Photic Stimulation;Sensory Deprivation;Visual Cortex;24 Pubmed search results 2008;21 Neurophysiology;Neuronal Plasticity;comparative study;research support, u.s. gov't, p.h.s.;Age Factors;Animals;Blindness;Dominance, Ocular;Mice}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Howard Hughes Medical Institute, The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.}, Pages = {917-23}, Pii = {S0896627304007950}, Pubmed = {15603735}, Title = {How monocular deprivation shifts ocular dominance in visual cortex of young mice}, Uuid = {0F60362E-8143-417A-B2ED-A68BFB765C5D}, Volume = {44}, Year = {2004}, url = {papers/Frenkel_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.12.003}} @article{Freundlieb:2006, Abstract = {The subventricular zone of the adult primate brain contains neural stem cells that can produce new neurons. Endogenous neurogenesis might therefore be used to replace lost neurons in neurodegenerative diseases. This would require, however, a precise understanding of the molecular regulation of stem cell proliferation and differentiation in vivo. Several regulatory factors, including dopamine, have been identified in rodents, but none in primates. We have, therefore, studied the origin and function of the dopaminergic innervation of the subventricular zone in nonhuman primates. Tracing experiments in three macaques revealed a topographically organized projection from the substantia nigra pars compacta (SNpc), but not the adjacent retrorubral field, to the subventricular zone: the anteromedial SNpc projects to the anteroventral subventricular zone, the posterolateral SNpc to the posterodorsal subventricular zone. Double immunolabeling for tyrosine hydroxylase and BrdU (5-bromo-2'deoxyuridine) incorporated into the DNA of proliferating cells showed that dopaminergic fibers approach proliferating cells in the subventricular zone. We investigated the effect of this nigro-subventricular projection on cell proliferation in six aged macaques, because the rate of neurogenesis differs between young adult and aged primates and because neurodegenerative diseases mainly affect aged humans. Three macaques were treated with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) to decrease dopaminergic innervation of the subventricular zone. A significant decrease in the number of PCNA+ (proliferating cell nuclear antigen-positive) proliferating cells (-44\%) and PSA-NCAM(+) (polysialylated neural cell adhesion molecule-positive) neuroblasts (-59\%) was found in the denervated regions of the subventricular zone, suggesting that an intact dopaminergic nigro-subventricular innervation is crucial for sustained neurogenesis in aged primates.}, Author = {Freundlieb, Nils and Fran\c{c}ois, Chantal and Tand{\'e}, Dominique and Oertel, Wolfgang H. and Hirsch, Etienne C. and H{\"o}glinger, G{\"u}nter U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Aging;Substantia Nigra;Tissue Distribution;Cell Differentiation;Research Support, Non-U.S. Gov't;24 Pubmed search results 2008;Macaca mulatta;Cell Proliferation;Neural Pathways;Stem Cells;Cercopithecus aethiops;Cerebral Ventricles;Cells, Cultured;Dopamine;Animals;Neurons}, Month = {2}, Nlm_Id = {8102140}, Number = {8}, Organization = {Experimental Neurology, Philipps University, D-35033 Marburg, Germany.}, Pages = {2321-5}, Pii = {26/8/2321}, Pubmed = {16495459}, Title = {Dopaminergic substantia nigra neurons project topographically organized to the subventricular zone and stimulate precursor cell proliferation in aged primates}, Uuid = {1129FCFA-C8AE-48D6-B133-D350DFCA78D7}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4859-05.2006}} @article{Fricker:1999, Abstract = {Neural progenitor cells obtained from the embryonic human forebrain were expanded up to 10(7)-fold in culture in the presence of epidermal growth factor, basic fibroblast growth factor, and leukemia inhibitory growth factor. When transplanted into neurogenic regions in the adult rat brain, the subventricular zone, and hippocampus, the in vitro propagated cells migrated specifically along the routes normally taken by the endogenous neuronal precursors: along the rostral migratory stream to the olfactory bulb and within the subgranular zone in the dentate gyrus, and exhibited site-specific neuronal differentiation in the granular and periglomerular layers of the bulb and in the dentate granular cell layer. The cells exhibited substantial migration also within the non-neurogenic region, the striatum, in a seemingly nondirected manner up to approximately 1-1.5 mm from the graft core, and showed differentiation into both neuronal and glial phenotypes. Only cells with glial-like features migrated over longer distances within the mature striatum, whereas the cells expressing neuronal phenotypes remained close to the implantation site. The ability of the human neural progenitors to respond in vivo to guidance cues and signals that can direct their differentiation along multiple phenotypic pathways suggests that they can provide a powerful and virtually unlimited source of cells for experimental and clinical transplantation.}, Author = {Fricker, R. A. and Carpenter, M. K. and Winkler, C. and Greco, C. and Gates, M. A. and Bjorklund, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurosci}, Keywords = {Cell Survival;Olfactory Bulb/physiology;Cell Differentiation;Human;Cells, Cultured;Rats;Female;Hippocampus/cytology/physiology;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Brain/cytology/*physiology;Animal;Cell Movement;Stem Cells/*cytology;Corpus Striatum/cytology/physiology;Cell Line;Support, Non-U.S. Gov't;B;Fetal Tissue Transplantation/*physiology;Brain Tissue Transplantation/*physiology;Transplantation, Heterologous/physiology;Neurons/*cytology/*physiology/transplantation}, Number = {14}, Organization = {Wallenberg Neuroscience Center, Division of Neurobiology, Lund University, S-223 Lund, Sweden.}, Pages = {5990-6005.}, Title = {Site-specific migration and neuronal differentiation of human neural progenitor cells after transplantation in the adult rat brain}, Uuid = {015B7B59-ADC4-484C-B552-879EE9A2507A}, Volume = {19}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10407037%20http://www.jneurosci.org/cgi/content/full/19/14/5990%20http://www.jneurosci.org/cgi/content/abstract/19/14/5990}} @article{Fricker-Gates:2004, Abstract = {Transplants of embryonic striatal tissue are characteristically heterogeneous, containing patches (P-zones) of striatal medium spiny projection neurons. It is not yet known how this morphology develops, and whether the striatal neurons in the grafts are derived from post-mitotic neuroblasts in the embryonic brain or from striatal progenitors that continue to divide after transplantation. To address this question we labelled dividing cells in the transplants with bromodeoxyuridine (BrdU), either prior to or after transplantation into the adult lesioned rat striatum. Cells for transplantation were either pre-labelled in utero by intraperitoneal (i.p.) injections of BrdU, or post-labelled after transplantation by i.p. injections to the hosts. Either two or six months after transplantation the brains were processed using double immunohistochemical techniques to detect BrdU and calbindin-positive neurons in the transplants. In the transplants pre-labelled with BrdU, approximately 30\%of calbindin-positive cells were heavily labelled with BrdU, suggesting these had undergone a final division prior to transplantation. In transplants where cells had been labelled post-transplantation, approximately 17\%of calbindin cells were heavily BrdU labelled. These results suggest that whereas a proportion of striatal medium spiny neurons in the striatal grafts were post-mitotic at the time of transplantation, other striatal progenitor cells can continue to divide after transplantation, and then complete an appropriate neuronal maturation programme in the adult host brain environment.}, Author = {Fricker-Gates, Rosemary A. and White, Anna and Gates, Monte A. and Dunnett, Stephen B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Cell Survival;Pregnancy;Animals;Corpus Striatum;Cells, Cultured;Aging;Brain Tissue Transplantation;Rats;Comparative Study;Mitosis;Phosphopyruvate Hydratase;Female;Cell Count;Calcium-Binding Protein, Vitamin D-Dependent;Ibotenic Acid;Embryo;Time Factors;Neurons;Transplants;Cell Division;24 Pubmed search results 2008;Immunohistochemistry;Stem Cells;Acetylcholinesterase;Bromodeoxyuridine;Research Support, Non-U.S. Gov't}, Month = {2}, Nlm_Id = {8918110}, Number = {3}, Organization = {School of Biosciences, Cardiff University, Cardiff, Wales.}, Pages = {513-20}, Pii = {3149}, Pubmed = {14984402}, Title = {Striatal neurons in striatal grafts are derived from both post-mitotic cells and dividing progenitors}, Uuid = {451975DC-A9B6-4BF4-977B-CCEFE0DF8355}, Volume = {19}, Year = {2004}} @article{Fried:2002, Abstract = {More chemicals can be smelled than there are olfactory receptors for them, necessitating a combinatorial representation by somewhat broadly tuned receptors. To understand the perception of odor quality and concentration, it is essential to establish the nature of the receptor repertoires that are activated by particular odorants at particular concentrations. We have taken advantage of the one-to-one correspondence of glomeruli and olfactory receptor molecules in the mouse olfactory bulb to analyze the tuning properties of a major receptor population by high resolution calcium imaging of odor responses selectively in the presynaptic compartment of glomeruli. We show that eighty different olfactory receptors projecting to the dorsal olfactory bulb respond to high concentrations of aldehydes with limited specificity. Varying ensembles of about 10 to 20 receptors encode any particular aldehyde at low stimulus concentrations with high specificity. Even normalized odor response patterns are markedly concentration dependent, caused by pronounced differences in affinity within the aldehyde receptor repertoire. Using Smart Source Parsing Feb}, Author = {Fried, H. U. and Fuss, S. H. and Korsching, S. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Organization = {Institute for Genetics, University of Cologne, Zulpicher Strasse 47, 50674 Cologne, Germany.}, Pages = {19}, Title = {Selective imaging of presynaptic activity in the mouse olfactory bulb shows concentration and structure dependence of odor responses in identified glomeruli}, Uuid = {201852AC-11D4-43AA-94C9-571D070DB07B}, Volume = {19}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11854464%20http://www.pnas.org/cgi/content/full/052658399v1%20http://www.pnas.org/cgi/content/abstract/052658399v1}} @article{Friedel:2007, Abstract = {Cerebellar granule cell progenitors proliferate postnatally in the upper part of the external granule cell layer (EGL) of the cerebellum. Postmitotic granule cells differentiate and migrate, tangentially in the EGL and then radially through the molecular and Purkinje cell layers. The molecular control of the transition between proliferation and differentiation in cerebellar granule cells is poorly understood. We show here that the transmembrane receptor Plexin-B2 is expressed by proliferating granule cell progenitors. To study Plexin-B2 function, we generated a targeted mutation of mouse Plexin-B2. Most Plexin-B2(-/-) mutants die at birth as a result of neural tube closure defects. Some mutants survive but their cerebellum cytoarchitecture is profoundly altered. This is correlated with a disorganization of the timing of granule cell proliferation and differentiation in the EGL. Many differentiated granule cells migrate inside the cerebellum and keep proliferating. These results reveal that Plexin-B2 controls the balance between proliferation and differentiation in granule cells.}, Author = {Friedel, Roland H. and Kerjan, G{\'e}raldine and Rayburn, Helen and Sch{\"u}ller, Ulrich and Sotelo, Constantino and Tessier-Lavigne, Marc and Ch{\'e}dotal, Alain}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;10 Development;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Department of Biological Sciences, Howard Hughes Medical Institute, Stanford University, Stanford, California 94305, USA.}, Pages = {3921-32}, Pii = {27/14/3921}, Pubmed = {17409257}, Title = {Plexin-B2 controls the development of cerebellar granule cells}, Uuid = {2D2A28EA-F315-4577-88DF-1B3626D22215}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4710-06.2007}} @article{Friedman:2004, Abstract = {High-throughput genome-wide molecular assays, which probe cellular networks from different perspectives, have become central to molecular biology. Probabilistic graphical models are useful for extracting meaningful biological insights from the resulting data sets. These models provide a concise representation of complex cellular networks by composing simpler submodels. Procedures based on well-understood principles for inferring such models from data facilitate a model-based methodology for analysis and discovery. This methodology and its capabilities are illustrated by several recent applications to gene expression data.}, Author = {Friedman, Nir}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:46 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Models, Biological;Mathematics;Computational Biology;Bayes Theorem;Gene Expression Regulation;Gene Expression Profiling;Gene Expression;Models, Statistical;review, tutorial;Models, Genetic;Support, Non-U.S. Gov't;Cell Physiology;review;23 Technique}, Month = {2}, Nlm_Id = {0404511}, Number = {5659}, Organization = {School of Computer Science and Engineering, Hebrew University, 91904 Jerusalem, Israel. nir\@cs.huji.ac.il}, Pages = {799-805}, Pii = {303/5659/799}, Pubmed = {14764868}, Title = {Inferring cellular networks using probabilistic graphical models}, Uuid = {311F933C-D057-47BC-862A-2D7766353E90}, Volume = {303}, Year = {2004}, url = {papers/Friedman_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1094068}} @article{Fries:2008, Abstract = {Neuronal gamma-band synchronization is central for cognition. Respective studies in human subjects focused on a visually induced transient enhancement of broadband EEG power. In this issue of Neuron, Yuval-Greenberg et al. demonstrate that this EEG response is an artifact of microsaccades, raising the question of whether gamma-band synchronization can be assessed with EEG.}, Author = {Fries, Pascal and Scheeringa, Ren{\'e} and Oostenveld, Robert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {Electroencephalography;Saccades;Evoked Potentials, Visual;comment;Cognition;Animals;Humans;24 Pubmed search results 2008;review;Artifacts}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {F.C. Donders Centre for Cognitive Neuroimaging, Radboud University Nijmegen, 6525 EN Nijmegen, The Netherlands. pascal.fries\@fcdonders.ru.nl}, Pages = {303-5}, Pii = {S0896-6273(08)00374-7}, Pubmed = {18466741}, Title = {Finding gamma}, Uuid = {1BDA3E30-5472-4BF8-B0EE-CD33F71DE2C2}, Volume = {58}, Year = {2008}, url = {papers/Fries_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.04.020}} @article{Friocourt:2003, Abstract = {Type I lissencephaly is a cortical malformation disorder characterized by disorganized cortical layers and gyral abnormalities and associated with severe cognitive impairment and epilepsy. The exact pathophysiological mechanisms underlying the epilepsy and mental retardation in this and related disorders remain unknown. Two genes, LIS1 and doublecortin, have both been shown to be mutated in a large proportion of cases of type I lissencephaly and a milder allelic disorder, subcortical laminar heterotopia (SCLH). Studying the protein products of these genes and the biochemical pathways in which they belong is likely to yield important information concerning both normal and abnormal cortical development. The relationships between the LIS1 and Doublecortin proteins are not yet well defined, but both are believed to play a critical role in cortical neuronal migration. Lis1 is expressed from very early development in the mouse and in both proliferating cells and post-mitotic neurons of the cortex. This protein is likely to have multiple functions since it is a subunit of the enzyme platelet-activating factor acetylhydrolase, which degrades platelet activating factor, and has also been shown to be involved in microtubule dynamics, potentially influencing nuclear migration through its interaction with the dynein motor protein complex. Doublecortin on the other hand is exclusively expressed in post-mitotic neurons and is developmentally regulated. In young developing neurons Doublecortin has a specific subcellular localization at the ends of neuritic and leading processes. This localization, combined with our previous data showing that it is a microtubule-associated protein and that it interacts with adapter complexes involved in vesicle trafficking, suggests a role in the growth of neuronal processes, downstream of directional or guidance signals. The observations summarized here favor the suggestion that whereas LIS1 may play a role in nuclear migration, Doublecortin is instead restricted to functions at the leading edge of the cell. 1047-3211 Journal Article Review Review, Tutorial}, Author = {Friocourt, G. and Koulakoff, A. and Chafey, P. and Boucher, D. and Fauchereau, F. and Chelly, J. and Francis, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Cereb Cortex}, Keywords = {Neuropeptides/genetics/*physiology;Nerve Tissue Proteins/metabolism;Cerebral Cortex/cytology/embryology/*physiology;10 Development;Gene Expression Regulation, Developmental;Microtubules/physiology;Neurons/cytology/*physiology;Cell Division;Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism;Astrocytes/metabolism;F;Microtubule-Associated Proteins/genetics/*physiology;Cell Movement/*physiology;Animals;Support, Non-U.S. Gov't;Mice}, Number = {6}, Organization = {Laboratoire de Genetique et Physiopathologie des Retards Mentaux, GDPM, Institut Cochin, 24 Rue du Faubourg Saint Jacques, F-75014 Paris, France.}, Pages = {620-6}, Pubmed = {12764037}, Title = {Doublecortin functions at the extremities of growing neuronal processes}, Uuid = {F768A71E-D0D3-4722-A13F-B02C852D9120}, Volume = {13}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12764037}} @article{Friocourt:2006, Abstract = {The ARX protein (encoded by the aristaless-related homeobox gene) is a member of the paired class of homeoproteins. More precisely, it is a member of the Aristaless subclass of proteins with a glutamine residue (Q) at the critical position 50 of the homeodomain (Q50). Through identification of diverse inherited or de novo mutations, genetic investigations of X-linked mental retardation conditions have demonstrated the implication of ARX in a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of X-linked mental retardation without apparent brain abnormalities. These investigations have recently directed attention to the role of this gene in brain development. Analysis of its spatiotemporal localization profile have revealed expression mainly in telencephalic structures at all stages of development. Interestingly, in adult, ARX expression becomes restricted to a population of GABAergic neurons. Although the identification of the target genes regulated by ARX remains a crucial step to better understanding its role during brain development, studies of the role of ARX orthologs in different models have indicated that it is essential for important developmental processes such as proliferation, cell differentiation and neuronal migration.}, Author = {Friocourt, Ga{\"e}lle and Poirier, Karine and Raki\'{c}, Sonja and Parnavelas, John G. and Chelly, Jamel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Homeodomain Proteins;Mutation;Gene Expression Regulation, Developmental;Research Support, Non-U.S. Gov't;24 Pubmed search results 2008;21 Neurophysiology;21 Epilepsy;Gene Expression;Animals;Humans;Cerebral Cortex;review;Transcription Factors}, Month = {2}, Nlm_Id = {8918110}, Number = {4}, Organization = {Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, UK.}, Pages = {869-76}, Pii = {EJN4629}, Pubmed = {16519652}, Title = {The role of ARX in cortical development}, Uuid = {8EE0A372-926A-4929-9E1B-CB994F6C1C46}, Volume = {23}, Year = {2006}, url = {papers/Friocourt_EurJNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.04629.x}} @article{Friocourt:2007, Abstract = {Type I lissencephaly, a genetic disease characterized by disorganized cortical layers and gyral abnormalities, is associated with severe cognitive impairment and epilepsy. Two genes, LIS1 and doublecortin (DCX), have been shown to be responsible for a large proportion of cases of type I lissencephaly. Both genes encode microtubule-associated proteins that have been shown to be important for radial migration of cortical pyramidal neurons. To investigate whether DCX also plays a role in cortical interneuron migration, we inactivated DCX in the ganglionic eminence of rat embryonic day 17 brain slices using short hairpin RNA. We found that, when DCX expression was blocked, the migration of interneurons from the ganglionic eminence to the cerebral cortex was slowed but not absent, similar to what had previously been reported for radial neuronal migration. In addition, the processes of DCX-deficient migrating interneurons were more branched than their counterparts in control experiments. These effects were rescued by DCX overexpression, confirming the specificity to DCX inactivation. A similar delay in interneuron migration was observed when Doublecortin-like kinase (DCLK), a microtubule-associated protein related to DCX, was inactivated, although the morphology of the cells was not affected. The importance of these genes in interneuron migration was confirmed by our finding that the cortices of Dcx, Dclk, and Dcx/Dclk mutant mice contained a reduced number of such cells in the cortex and their distribution was different compared with wild-type controls. However, the defect was different for each group of mutant animals, suggesting that DCX and DCLK have distinct roles in cortical interneuron migration.}, Author = {Friocourt, Ga{\"e}lle and Liu, Judy S. and Antypa, Mary and Rakic, Sonja and Walsh, Christopher A. and Parnavelas, John G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;10 Development;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.}, Pages = {3875-83}, Pii = {27/14/3875}, Pubmed = {17409252}, Title = {Both doublecortin and doublecortin-like kinase play a role in cortical interneuron migration}, Uuid = {400F1113-7961-4560-8B0E-83AFC00DCA91}, Volume = {27}, Year = {2007}, url = {papers/Friocourt_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4530-06.2007}} @article{Fritschy:1994, Abstract = {The involvement of GABA in neuronal differentiation and maturation precedes its role as inhibitory neurotransmitter in the brain. It was therefore investigated whether GABAA receptors mediating the actions of GABA in neonatal and adult brain can be distinguished by their molecular structure and cellular location. Immunohistochemistry with subunit-specific antibodies was employed to analyze changes in the distribution of GABAA-receptor subunits during postnatal development. In particular, subunit association patterns, as evidenced by colocalization of subunits within individual neurons, were analyzed by confocal laser microscopy. The subunits analyzed include the alpha 1- and alpha 2-subunits, which are associated with pharmacologically distinct GABAA-receptor subtypes, and the beta 2,3-subunits, which are a major constituent of GABAA receptors in both immature and adult rat brain. Each of these subunits exhibited age-dependent changes in their distribution, indicative of a differential maturation process. The alpha1-subunit immunoreactivity (-IR) was low at birth, restricted to a few areas, and increased dramatically during the first postnatal weeks. By contrast, the alpha 2-subunit-IR displayed a widespread distribution throughout the brain at birth, and disappeared from numerous areas soon after the appearance of the alpha 1-subunit. Double-immunofluorescence staining demonstrated the coexistence of both subunits in many individual neurons during a short time window, indicating that receptors containing the alpha 1-subunit gradually replace receptors containing the alpha 2-subunit in these cells. Staining for the beta 2,3-subunits was prominent and ubiquitous at every developmental age, indicating that these subunits are present in both neonatal and adult GABAA receptors. Indeed, double-immunofluorescence staining revealed an extensive colocalization of the alpha 2- and beta 2,3-subunits in neurons from neonatal rats, whereas the beta 2,3-subunits were associated with the alpha 1-subunit at later stages. Thus, the onset of alpha 1-subunit staining in maturing brain is indicative for the expression of a new, prevalent receptor subtype, presumably involved in synaptic inhibition. These findings demonstrate a switch in the subunit composition of GABAA receptors during postnatal development, suggesting the existence of molecularly distinct immature and adult forms of GABAA receptors in rat CNS.}, Author = {Fritschy, J. M. and Paysan, J. and Enna, A. and Mohler, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurosci}, Keywords = {Tissue Distribution;Rats, Sprague-Dawley;Receptors, GABA/*metabolism/physiology;Immunohistochemistry;Rats;Animal;I-3;Neuroglia/metabolism;Aging/*metabolism;Support, Non-U.S. Gov't;Animals, Newborn/growth &development/*metabolism;Brain/cytology/*metabolism;13 Olfactory bulb anatomy}, Number = {9}, Organization = {University of Zurich, Institute of Pharmacology, Switzerland.}, Pages = {5302-24.}, Title = {Switch in the expression of rat GABAA-receptor subtypes during postnatal development: an immunohistochemical study}, Uuid = {AA61B16B-29CF-4D55-A83D-10752D69E8DF}, Volume = {14}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8083738}} @article{Frotscher:2003, Abstract = {Reelin, synthesized and secreted by Cajal-Retzius (CR) cells in the marginal zone of the cortex, is an extracellular matrix protein important for the development of cortical layers. In reeler mutant mice lacking Reelin, there are severe malformations of neocortical and hippocampal lamination. It has been assumed that Reelin acts as a stop signal for migrating neurons. Here we show, by using the dentate gyrus as a model in in vivo studies and in vitro assays, that Reelin exerts its effects, at least in part, by acting on the radial glial scaffold required for neuronal migration. Migration defects of dentate granule cells, reminiscent of those seen in reeler mutants, are observed in tissue from patients with temporal lobe epilepsy (TLE). The extent of granule cell dispersion in TLE was found to be inversely correlated with the number of reelin mRNA synthesizing CR cells and reelin mRNA expression as revealed in quantitative RT-PCR studies. These findings show that the Reelin signaling pathway is essential for the correct positioning of human hippocampal neurons and that a Reelin deficiency is involved in the pathological changes associated with epilepsy.}, Author = {Frotscher, Michael and Haas, Carola A. and F{\"o}rster, Eckart}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Signal Transduction;Animals;Gene Expression Regulation;Kidney;Humans;Comparative Study;Cell Movement;Hippocampus;Reference Values;Cell Adhesion Molecules, Neuronal;Cell Line;Extracellular Matrix Proteins;Mice, Knockout;Neuroglia;Epilepsy, Temporal Lobe;Dentate Gyrus;Neurons;Adult;Mice;Research Support, Non-U.S. Gov't}, Medline = {22648203}, Month = {6}, Nlm_Id = {9110718}, Number = {6}, Organization = {Anatomisches Institut, Universit{\"a}t Freiburg, Albertstrasse 17, D-79104 Freiburg, Germany. michael.frotscher\@anat.uni-freiburg.de}, Pages = {634-40}, Pubmed = {12764039}, Title = {Reelin controls granule cell migration in the dentate gyrus by acting on the radial glial scaffold}, Uuid = {021B383A-716E-11DA-A383-000D9346EC2A}, Volume = {13}, Year = {2003}, url = {papers/Frotscher_CerebCortex2003.pdf}} @article{Frotscher:1998, Abstract = {Early-generated Cajal-Retzius cells in the marginal zone of the cortex synthesize and secrete the glycoprotein Reelin. The reelin gene is deleted in reeler mice, which show characteristic alterations in cortical lamination. Recent studies have shed some light on the role of Cajal-Retzius cells and Reelin in the formation of cell and fiber layers in the neocortex and hippocampus.}, Author = {Frotscher, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {review;10 Development;Research Support, Non-U.S. Gov't;Extracellular Matrix Proteins;Hippocampus;10 Hippocampus;Nerve Tissue Proteins;Neocortex;review, tutorial;Mice;Animals;Cell Adhesion Molecules, Neuronal;Mice, Neurologic Mutants;Neurons}, Medline = {99035600}, Month = {10}, Nlm_Id = {9111376}, Number = {5}, Organization = {Institute of Anatomy, University of Freiburg, Germany. frotsch\@uni-freiburg.de}, Pages = {570-5}, Pubmed = {9811621}, Title = {Cajal-Retzius cells, Reelin, and the formation of layers}, Uuid = {E6DE3558-E453-408B-91BF-4FE890EDAA1B}, Volume = {8}, Year = {1998}} @article{Frohlich:2006, Abstract = {Little is known about the dynamics and mechanisms of transitions between tonic firing and bursting in cortical networks. Here, we use a computational model of a neocortical circuit with extracellular potassium dynamics to show that activity-dependent modulation of intrinsic excitability can lead to sustained oscillations with slow transitions between two distinct firing modes: fast run (tonic spiking or fast bursts with few spikes) and slow bursting. These transitions are caused by a bistability with hysteresis in a pyramidal cell model. Balanced excitation and inhibition stabilizes a network of pyramidal cells and inhibitory interneurons in the bistable region and causes sustained periodic alternations between distinct oscillatory states. During spike-wave seizures, neocortical paroxysmal activity exhibits qualitatively similar slow transitions between fast run and bursting. We therefore predict that extracellular potassium dynamics can cause alternating episodes of fast and slow oscillatory states in both normal and epileptic neocortical networks.}, Author = {Fr{\"o}hlich, Flavio and Bazhenov, Maxim and Timofeev, Igor and Steriade, Mircea and Sejnowski, Terrence J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Electrophysiology;Electric Conductivity;Synapses;Animals;Humans;Neocortex;Reaction Time;Extracellular Fluid;research support, non-u.s. gov't;Potassium;Nerve Net;21 Neurophysiology;Neurons;research support, n.i.h., extramural;24 Pubmed search results 2008;Cats;Models, Neurological;Oscillometry}, Month = {6}, Nlm_Id = {8102140}, Number = {23}, Organization = {The Salk Institute for Biological Studies, Computational Neurobiology Laboratory, Howard Hughes Medical Institute, La Jolla, California 92037, USA.}, Pages = {6153-62}, Pii = {26/23/6153}, Pubmed = {16763023}, Title = {Slow state transitions of sustained neural oscillations by activity-dependent modulation of intrinsic excitability}, Uuid = {FDBE7B87-91A6-45C1-A772-5480CBD8AC81}, Volume = {26}, Year = {2006}, url = {papers/Fröhlich_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5509-05.2006}} @article{Frohlich:2008, Abstract = {Slow periodic EEG discharges are common in CNS disorders. The pathophysiology of this aberrant rhythmic activity is poorly understood. We used a computational model of a neocortical network with a dynamic homeostatic scaling rule to show that loss of input (partial deafferentation) can trigger network reorganization that results in pathological periodic discharges. The decrease in average firing rate in the network by deafferentation was compensated by homeostatic synaptic scaling of recurrent excitation among pyramidal cells. Synaptic scaling succeeded in recovering the network target firing rate for all degrees of deafferentation (fraction of deafferented cells), but there was a critical degree of deafferentation for pathological network reorganization. For deafferentation degrees below this value, homeostatic upregulation of recurrent excitation had minimal effect on the macroscopic network dynamics. For deafferentation above this threshold, however, a slow periodic oscillation appeared, patterns of activity were less sparse, and bursting occurred in individual neurons. Also, comparison of spike-triggered afferent and recurrent excitatory conductances revealed that information transmission was strongly impaired. These results suggest that homeostatic plasticity can lead to secondary functional impairment in case of cortical disorders associated with cell loss.}, Author = {Fr{\"o}hlich, Flavio and Bazhenov, Maxim and Sejnowski, Terrence J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Animals;Synapses;Encephalitis;Sodium Channels;Neuronal Plasticity;Humans;Homeostasis;Neurons, Afferent;Brain Diseases;Computer Simulation;Nerve Net;Cerebral Cortex;21 Neurophysiology;Potassium Channels, Voltage-Gated;research support, n.i.h., extramural;Interneurons;24 Pubmed search results 2008;Electroencephalography;Models, Neurological}, Month = {2}, Nlm_Id = {8102140}, Number = {7}, Organization = {The Salk Institute for Biological Studies, Computational Neurobiology Laboratory, La Jolla, California 92037, USA.}, Pages = {1709-20}, Pii = {28/7/1709}, Pubmed = {18272691}, Title = {Pathological effect of homeostatic synaptic scaling on network dynamics in diseases of the cortex}, Uuid = {45640911-826C-428A-967D-7B9D343670E6}, Volume = {28}, Year = {2008}, url = {papers/Fröhlich_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4263-07.2008}} @article{Fuchs:2004, Abstract = {The potential of stem cells in regenerative medicine relies upon removing them from their natural habitat, propagating them in culture, and placing them into a foreign tissue environment. To do so, it is essential to understand how stem cells interact with their microenvironment, the so-called stem cell niche, to establish and maintain their properties. In this review, we examine adult stem cell niches and their impact on stem cell biology. 0092-8674 Journal Article}, Author = {Fuchs, E. and Tumbar, T. and Guasch, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Cell}, Keywords = {02 Adult neurogenesis migration;BB pdf;03 Adult neurogenesis progenitor source}, Number = {6}, Organization = {Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA. fuchslb\@rockefeller.edu}, Pages = {769-78}, Title = {Socializing with the neighbors: stem cells and their niche}, Uuid = {D9EAE568-620A-4AEA-8E4D-0B5E36673000}, Volume = {116}, Year = {2004}, url = {papers/Fuchs_Cell2004.pdf}} @article{Fuchs:2007, Abstract = {With the growing recognition that rhythmic and oscillatory patterns are widespread in the brain and play important roles in all aspects of the function of our nervous system, there has been a resurgence of interest in neuronal synchronized bursting activity. Here, we were interested in understanding the development of synchronized bursts as information-bearing neuronal activity patterns. For that, we have monitored the morphological organization and spontaneous activity of neuronal networks cultured on multielectrode-arrays during their self-executed evolvement from a mixture of dissociated cells into an active network. Complex collective network electrical activity evolved from sporadic firing patterns of the single neurons. On the system (network) level, the activity was marked by bursting events with interneuronal synchronization and nonarbitrary temporal ordering. We quantified these individual-to-collective activity transitions using newly-developed system level quantitative measures of time series regularity and complexity. We found that individual neuronal activity before synchronization was characterized by high regularity and low complexity. During neuronal wiring, there was a transient period of reorganization marked by low regularity, which then leads to coemergence of elevated regularity and functional (nonstochastic) complexity. We further investigated the morphology-activity interplay by modeling artificial neuronal networks with different topological organizations and connectivity schemes. The simulations support our experimental results by showing increased levels of complexity of neuronal activity patterns when neurons are wired up and organized in clusters (similar to mature real networks), as well as network-level activity regulation once collective activity forms.}, Author = {Fuchs, E. and Ayali, A. and Robinson, A. and Hulata, E. and Ben-Jacob, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1932-8451}, Journal = {Dev Neurobiol}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {101300215}, Number = {13}, Organization = {Department of Zoology, Tel-Aviv University, Tel-Aviv 69978, Israel.}, Pages = {1802-14}, Pubmed = {17701997}, Title = {Coemergence of regularity and complexity during neural network development}, Uuid = {073AF7DB-8882-4905-8ACB-B5ED8E47F8A1}, Volume = {67}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dneu.20557}} @article{Fuchs:2000, Author = {Fuchs, E. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Eur J Neurosci}, Keywords = {01 Adult neurogenesis general;Mammals;Brain/*cytology/*physiology;Cell Differentiation/physiology;Neurons/*cytology;Animal;A-9b;Age Factors}, Number = {7}, Organization = {Division of Neurobiology, German Primate Center, Gottingen, Germany. efuchs\@gwdg.de}, Pages = {2211-4.}, Title = {Mini-review: in vivo neurogenesis in the adult brain: regulation and functional implications}, Uuid = {58B572B0-CC41-4E13-80FF-91A23DED5DAA}, Volume = {12}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10947799}} @article{Fuerst:2008, Abstract = {To establish functional circuitry, retinal neurons occupy spatial domains by arborizing their processes, which requires the self-avoidance of neurites from an individual cell, and by spacing their cell bodies, which requires positioning the soma and establishing a zone within which other cells of the same type are excluded. The mosaic patterns of distinct cell types form independently and overlap. The cues that direct these processes in the vertebrate retina are not known. Here we show that some types of retinal amacrine cells from mice with a spontaneous mutation in Down syndrome cell adhesion molecule (Dscam), a gene encoding an immunoglobulin-superfamily member adhesion molecule, have defects in the arborization of processes and in the spacing of cell bodies. In the mutant retina, cells that would normally express Dscam have hyperfasciculated processes, preventing them from creating an orderly arbor. Also, their cell bodies are randomly distributed or pulled into clumps rather than being regularly spaced mosaics. Our results indicate that mouse DSCAM mediates isoneuronal self-avoidance for arborization and heteroneuronal self-avoidance within specific cell types to prevent fasciculation and to preserve mosaic spacing. These functions are analogous to those of Drosophila DSCAM (ref. 6) and DSCAM2 (ref. 7). DSCAM may function similarly in other regions of the mammalian nervous system, and this role may extend to other members of the mammalian Dscam gene family.}, Author = {Fuerst, Peter G. and Koizumi, Amane and Masland, Richard H. and Burgess, Robert W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Retina;Neurites;10 Development;research support, non-u.s. gov't;Gene Deletion;Amacrine Cells;10 circuit formation;RNA Stability;research support, n.i.h., extramural;Animals;Cell Movement;Mice;Proteins;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0410462}, Number = {7177}, Organization = {The Jackson Laboratory, Bar Harbor, Maine 04609, USA.}, Pages = {470-4}, Pii = {nature06514}, Pubmed = {18216855}, Title = {Neurite arborization and mosaic spacing in the mouse retina require DSCAM}, Uuid = {103A59B9-5ABB-497D-9CB3-F5B3977D43C4}, Volume = {451}, Year = {2008}, url = {papers/Fuerst_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06514}} @article{Fueyo:2003, Abstract = {BACKGROUND: Oncolytic adenoviruses are promising therapies for the treatment of gliomas. However, untargeted viral replication and the paucity of coxsackie-adenovirus receptors (CARs) on tumor cells are major stumbling blocks for adenovirus-based treatment. We studied the antiglioma activity of the tumor-selective Delta-24 adenovirus, which encompasses an early 1 A adenoviral (E1A) deletion in the retinoblastoma (Rb) protein-binding region, and of the Delta-24-RGD adenovirus. Delta-24-RGD has an RGD-4C peptide motif inserted into the adenoviral fiber, which allows the adenovirus to anchor directly to integrins. METHODS: CAR and integrin expression were examined by flow cytometry in six glioma cell lines and in normal human astrocytes (NHAs). Adenoviral vectors containing green fluorescent protein (GFP) (AdGFP and AdGFP-RGD) were used to infect glioma cell lines with high or low CAR expression. Viability of glioma cells infected with different adenoviruses was assessed by trypan blue staining. Adenovirus replication was quantified with the infection-dose replication assay. Athymic mice carrying glioma xenografts received intratumoral injections of Delta-24-RGD or Delta-24 and were followed for survival, which was analyzed by the Kaplan-Meier method and the log-rank test. All statistical tests were two-sided. RESULTS: Half the glioma cell lines expressed low levels of CAR (defined as <50\%of cells expressing detectable CAR); all lines expressed integrins in more than 50\%of cells. Infection of U-87 MG cells (a low-CAR-expressing line) with AdGFP-RGD resulted in approximately six times more GFP-positive cells than infection with AdGFP. Delta-24-RGD was more cytopathic to both low- and high-CAR-expressing glioma lines than Delta-24, and it replicated more efficiently in both cell lines. In the xenografted mice, intratumoral injection of Delta-24-RGD was associated with longer survival than intratumoral injection of Delta-24 (P<.001, log-rank test). Furthermore, 60\%of Delta-24-RGD-treated mice but only 15\%of Delta-24-treated mice survived more than 4 months (difference = 45\%, 95\%CI = 21\%to 68\%). CONCLUSIONS: The antitumor activity of Delta-24-RGD suggests that it has the potential to be an effective agent in the treatment of gliomas. 1460-2105 Journal Article}, Author = {Fueyo, J. and Alemany, R. and Gomez-Manzano, C. and Fuller, G. N. and Khan, A. and Conrad, C. A. and Liu, T. J. and Jiang, H. and Lemoine, M. G. and Suzuki, K. and Sawaya, R. and Curiel, D. T. and Yung, W. K. and Lang, F. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Natl Cancer Inst}, Keywords = {Fluorescent Dyes;Human;Gene Expression Regulation, Neoplastic;Animals;Tumor Markers, Biological/*analysis;Trypan Blue;Retinoblastoma;Injections, Intralesional;Integrins/analysis;Transplantation, Heterologous;Calcium-Binding Proteins/*analysis;15 Retrovirus mechanism;J pdf;Brain Neoplasms/drug therapy/immunology/pathology/radiotherapy/*therapy;Dyes;Mice, Nude;Support, Non-U.S. Gov't;Tumor Cells, Cultured;Flow Cytometry;*Adenoviridae;Mice;Immunohistochemistry;Antigens, Neoplasm/*analysis;Astrocytes/immunology;Glioma/drug therapy/immunology/pathology/radiotherapy/*therapy}, Number = {9}, Organization = {Department of Neuro-Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. jfueyo\@mdanderson.org}, Pages = {652-60}, Pubmed = {12734316}, Title = {Preclinical characterization of the antiglioma activity of a tropism-enhanced adenovirus targeted to the retinoblastoma pathway}, Uuid = {8972B1EB-F38E-459C-A2D5-71ED9D19E95F}, Volume = {95}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12734316}} @article{Fuhrmann:2002, Abstract = {Spike-frequency adaptation in neocortical pyramidal neurons was examined using the whole cell patch-clamp technique and a phenomenological model of neuronal activity. Noisy current was injected to reproduce the irregular firing typically observed under in vivo conditions. The response was quantified by computing the poststimulus histogram (PSTH). To simulate the spiking activity of a pyramidal neuron, we considered an integrate-and-fire model to which an adaptation current was added. A simplified model for the mean firing rate of an adapting neuron under noisy conditions is also presented. The mean firing rate model provides a good fit to both experimental and simulation PSTHs and may therefore be used to study the response characteristics of adapting neurons to various input currents. The models enable identification of the relevant parameters of adaptation that determine the shape of the PSTH and allow the computation of the response to any change in injected current. The results suggest that spike frequency adaptation determines a preferred frequency of stimulation for which the phase delay of a neuron's activity relative to an oscillatory input is zero. Simulations show that the preferred frequency of single neurons dictates the frequency of emergent population rhythms in large networks of adapting neurons. Adaptation could therefore be one of the crucial factors in setting the frequency of population rhythms in the neocortex.}, Author = {Fuhrmann, Galit and Markram, Henry and Tsodyks, Misha}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Neural Networks (Computer);21 Neurophysiology;Action Potentials;Rats;Neocortex;Rats, Wistar;Electrophysiology;Somatosensory Cortex;Animals;Patch-Clamp Techniques;Membrane Potentials;Periodicity;21 Cortical oscillations}, Medline = {22153547}, Month = {8}, Nlm_Id = {0375404}, Number = {2}, Organization = {Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.}, Pages = {761-70}, Pubmed = {12163528}, Title = {Spike frequency adaptation and neocortical rhythms}, Uuid = {2AA63A3D-2990-4655-B1A3-9E48AD7ABEBA}, Volume = {88}, Year = {2002}} @article{Fujii:2002, Abstract = {BACKGROUND/AIMS: We examined whether bone marrow (BM) cells can commit to liver-consisting cells during liver regeneration after partial hepatectomy, using mice transplanted with green fluorescent protein (GFP) positive BM from GFP transgenic mice. METHODS: Partial hepatectomy or sham operation was performed. Lineage marker analysis of GFP positive liver cells was by immunostaining and flow cytometry. DiI-labeled acetylated low-density lipoprotein uptake or microsphere phagocytosis was examined in vitro. Lineage marker expression in BM and peripheral blood (PB) cells, and the vascular endothelial growth factor (VEGF) concentration in the liver were also examined. RESULTS: In hepatectomized mice, significantly more GFP positive cells participated in liver sinusoid than in sham-operated mice, expressing CD31 but not albumin. The percentage of cells that incorporated acetylated low-density lipoprotein but not microspheres was 69.5+/-3.4\%, while 28.3+/-2.6\%incorporated both, revealing sinusoidal endothelial and Kupffer cells, respectively. Increased expression of the CD31 and CD16/CD32 on GFP positive liver cells was also detected. The elevation of the VEGF concentration during liver regeneration and the increase in the CD34 and Flk-1 expression in the liver, BM, and PB cells suggested endothelial progenitor cell mobilization. CONCLUSIONS: GFP cell-marking provided direct evidence of the BM cells participation in liver regeneration after hepatectomy, where the majority was committed to sinusoidal endothelial cells probably through endothelial progenitor cell mobilization.}, Author = {Fujii, Hideaki and Hirose, Tetsuro and Oe, Shoshiro and Yasuchika, Kentaro and Azuma, Hisaya and Fujikawa, Takahisa and Nagao, Masaya and Yamaoka, Yoshio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0168-8278}, Journal = {J Hepatol}, Keywords = {Cell Differentiation;Green Fluorescent Proteins;Immunohistochemistry;Luminescent Proteins;Vascular Endothelial Growth Factor A;Animals;Hepatectomy;Phagocytosis;Flow Cytometry;Genes, Reporter;In Vitro;Liver Regeneration;Liver;Vascular Endothelial Growth Factor Receptor-2;Bone Marrow Transplantation;Mice, Inbred C57BL;11 Glia;Endothelial Growth Factors;Antigens, CD34;Intercellular Signaling Peptides and Proteins;Lymphokines;Bone Marrow Cells;Stem Cells;Indicators and Reagents;Mice;Research Support, Non-U.S. Gov't;Mice, Transgenic;Lipoproteins, LDL;Vascular Endothelial Growth Factors;Microscopy, Fluorescence}, Medline = {21979759}, Month = {5}, Nlm_Id = {8503886}, Number = {5}, Organization = {Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, 54, Kawara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. hideaki\@kuhp.kyoto-u.ac.jp}, Pages = {653-9}, Pii = {S0168827802000430}, Pubmed = {11983449}, Title = {Contribution of bone marrow cells to liver regeneration after partial hepatectomy in mice}, Uuid = {5659871C-3E9F-4082-B8FC-3DD7B7CB73B7}, Volume = {36}, Year = {2002}, url = {papers/Fujii_JHepatol2002.pdf}} @article{Fujioka:2004, Abstract = {Previous studies have demonstrated that activation of the cAMP cascade, including the cAMP response element-binding protein (CREB), increases the proliferation and survival of newborn neurons in adult mouse hippocampus. In the present study, we determined whether the cAMP-CREB cascade also influences the morphological maturation of newborn neurons in the subgranular zone of the hippocampus. Rolipram, a selective inhibitor of the cAMP-specific phosphodiesterase type 4, was administered to activate the cAMP cascade, and neuronal morphology was determined by analysis of Golgi-impregnated neurons in the subgranular zone of hippocampus. Rolipram administration significantly increased the number of branch points and length of dendrites relative to vehicle treatment. Increased branch number and length were accompanied by increased levels of phosphorylated CREB, the active form of this transcription factor, in immature neurons. In contrast, the morphology of Golgi-impregnated neurons was not significantly influenced by rolipram treatment in inducible transgenic mice expressing a dominant-negative mutant of CREB in hippocampus. We also tested the influence of cAMP analogs in primary hippocampal cultures and found that activation of the cAMP pathway increased and inhibition of the cAMP cascade decreased the number of branches and length of processes as observed in vivo. These findings indicate that the cAMP-CREB cascade plays an important role in the differentiation and maturation of newborn neurons in hippocampus. 1529-2401 Journal Article}, Author = {Fujioka, T. and Fujioka, A. and Duman, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {J Neurosci}, Keywords = {C pdf;04 Adult neurogenesis factors}, Number = {2}, Organization = {Division of Molecular Psychiatry, Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, Yale University School of Medicine, New Haven, Connecticut 06508, USA.}, Pages = {319-28}, Pubmed = {14724230}, Title = {Activation of cAMP signaling facilitates the morphological maturation of newborn neurons in adult hippocampus}, Uuid = {FDDFD87E-5A6C-4E49-A2D0-5D97BDD25EC0}, Volume = {24}, Year = {2004}, url = {papers/Fujioka_JNeurosci2004.pdf}} @article{Fujisawa:2006, Abstract = {Fluctuations of membrane potential of cortical neurons, referred to here as internal states, are essential for brain function, but little is known about how these internal states emerge and are maintained, or what determines transitions between these states. We performed intracellular recordings from hippocampal CA3 pyramidal cells ex vivo and found that neurons display multiple and hierarchical internal states, which are linked to cholinergic activity and are characterized by several power law structures in membrane potential dynamics. Multiple recordings from adjacent neurons revealed that the internal states were coherent between neurons, indicating that the internal state of any given cell in a local network could represent the network activity state. Repeated stimulation of single neurons led over time to transitions to different internal states in both the stimulated neuron and neighboring neurons. Thus, single-cell activation is sufficient to shift the state of the entire local network. As the states shift to more active levels, theta- and gamma-frequency components developed in the form of subthreshold oscillations. State transitions were associated with changes in membrane conductance but were not accompanied by a change in reversal potential. These data suggest that the recurrent network organizes the internal states of individual neurons into synchronization through network activity with balanced excitation and inhibition, and that this organization is discrete, heterogeneous and dynamic in nature. Thus, neuronal states reflect the 'phase' of an active network, a novel demonstration of the dynamics and flexibility of cortical microcircuitry.}, Author = {Fujisawa, Shigeyoshi and Matsuki, Norio and Ikegaya, Yuji}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Electrophysiology;Animals;Synapses;Rats;Algorithms;Muscarinic Agonists;Hippocampus;Pyramidal Cells;Rats, Wistar;research support, non-u.s. gov't;Organ Culture Techniques;Muscarinic Antagonists;Male;Computer Simulation;Nerve Net;Cerebral Cortex;21 Neurophysiology;Neurons;Atropine;Membrane Potentials;Carbachol;24 Pubmed search results 2008;Models, Neurological;in vitro}, Month = {5}, Nlm_Id = {9110718}, Number = {5}, Organization = {Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.}, Pages = {639-54}, Pii = {bhj010}, Pubmed = {16093564}, Title = {Single neurons can induce phase transitions of cortical recurrent networks with multiple internal States}, Uuid = {429FDB0F-10E9-462F-8F2F-BA3DC7852629}, Volume = {16}, Year = {2006}, url = {papers/Fujisawa_CerebCortex2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhj010}} @article{Fujisawa:1998, Abstract = {The tempo and intensity of retroviral neuropathogenesis are dependent on the capacity of the virus to invade the central nervous system. For murine leukemia viruses, an important determinant of neuroinvasiveness is the virus-encoded protein glycosylated Gag, the function of which in the virus life cycle is not known. While this protein is dispensable for virus replication, mutations which prevent its expression slow the spread of virus in vivo and restrict virus dissemination to the brain. To further explore the function of this protein, we compared two viruses, CasFrKP (KP) and CasFrKP41 (KP41), which differ dramatically in neurovirulence. KP expresses high early viremia titers, is neuroinvasive, and induces clinical neurologic disease in 100\%of neonatally inoculated mice, with an incubation period of 18 to 23 days. In contrast, KP41 expresses early viremia titers 100- fold lower than those of KP, exhibits attenuated neuroinvasiveness, and induces clinical neurologic disease infrequently, with a relatively long incubation period. The genomes of these two viruses differ by only 10 nucleotides, resulting in differences at five residues, all located within the N-terminal cytoplasmic tail of glycosylated Gag. In this study, using KP as the parental virus, we systematically mutated each of the five amino acid residues to those of KP41 and found that substitution mutation of two membrane-proximal residues, E53 and L56, to K and P, respectively produced the greatest effect on early viremia kinetics and neurovirulence. These mutations disrupted the KP sequence E53FLL56, the leucine dipeptide of which suggests the possibility that it may represent a sorting signal for glycosylated Gag. Supporting this idea was the finding that alteration of this sequence motif increased the level of cell surface expression of the protein, which suggests that analysis of the intracellular trafficking of glycosylated Gag may provide further clues to its function.}, Author = {Fujisawa, R. and McAtee, F. J. and Wehrly, K. and Portis, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Leukemia Virus, Murine;Viremia;Virulence;Gene Products, gag;Molecular Sequence Data;Cytoplasm;Glycosylation;Leucine;Not relevant;11 Glia;Amino Acid Sequence;Support, U.S. Gov't, P.H.S.;Mice;Animals;Brain;Spleen;Support, Non-U.S. Gov't}, Medline = {98285718}, Month = {7}, Nlm_Id = {0113724}, Number = {7}, Organization = {Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, Hamilton, Montana 59840, USA.}, Pages = {5619-25}, Pubmed = {9621020}, Title = {The neuroinvasiveness of a murine retrovirus is influenced by a dileucine-containing sequence in the cytoplasmic tail of glycosylated Gag}, Uuid = {76420E59-D360-4B88-AC79-C78F2620EA46}, Volume = {72}, Year = {1998}, url = {papers/Fujisawa_JVirol1998.pdf}} @article{Fukami:2003, Abstract = {Identification of the causes of productivity-species diversity relationships remains a central topic of ecological research. Different relations have been attributed to the influence of disturbance, consumers, niche specialization and spatial scale. One unexplored cause is the history of community assembly, the partly stochastic sequential arrival of species from a regional pool of potential community members. The sequence of species arrival can greatly affect community structure. If assembly sequence interacts with productivity to influence diversity, different sequences can contribute to variation in productivity-diversity relationships. Here we report a test of this hypothesis by assembling aquatic microbial communities at five productivity levels using four assembly sequences. About 30 generations after assembly, productivity-diversity relationships took various forms, including a positive, a hump-shaped, a U-shaped and a non-significant pattern, depending on assembly sequence. This variation resulted from idiosyncratic joint effects of assembly sequence, productivity and species identity on species abundances. We suggest that the history of community assembly should be added to the growing list of factors that influence productivity-biodiversity patterns.}, Author = {Fukami, Tadashi and Morin, Peter J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Models, Biological;Water Microbiology;research support, non-u.s. gov't;Population Dynamics;Algae;Bacterial Physiology;Stochastic Processes;Environment;Ecosystem;research support, u.s. gov't, non-p.h.s.;24 Pubmed search results 2008;Fresh Water}, Month = {7}, Nlm_Id = {0410462}, Number = {6947}, Organization = {Department of Ecology and Evolutionary Biology, University of Tennessee, Knoxville, Tennessee 37996-1610, USA. tfukami\@utk.edu}, Pages = {423-6}, Pii = {nature01785}, Pubmed = {12879069}, Title = {Productivity-biodiversity relationships depend on the history of community assembly}, Uuid = {14358360-C71D-4C1B-B485-8B5A47AD9CB7}, Volume = {424}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01785}} @article{Fukuda:2003, Abstract = {Neurogenesis in the dentate gyrus of the adult mammalian hippocampus has been proven in a series of studies, but the differentiation process toward newborn neurons is still unclear. In addition to the immunohistochemical study, electrophysiological membrane recordings of precursor cells could provide an alternative view to address this differentiation process. In this study, we performed green fluorescent protein (GFP)-guided selective recordings of nestin-positive progenitor cells in adult dentate gyrus by means of nestin-promoter GFP transgenic mice, because nestin is a typical marker for precursor cells in the adult dentate gyrus. The patch-clamp recordings clearly demonstrated the presence of two distinct subpopulations (type I and type II) of nestin-positive cells. Type I cells had a lower input resistance value of 77.1 M(Omega) (geometric mean), and their radial processes were stained with anti-glial fibrillary acidic protein antibody. On the other hand, type II nestin-positive cells had a higher input resistance value of 2110 MOmega and expressed voltage-dependent sodium current. In most cases, type II cells were stained with anti-polysialylated neural cell adhesion molecule. Taken together with a bromodeoxyuridine pulse-chase analysis, our results may reflect a rapid and dynamic cell conversion of nestin-positive progenitor, from type I to type II, at an early stage of adult neurogenesis in the dentate gyrus.}, Author = {Fukuda, Satoshi and Kato, Fusao and Tozuka, Yusuke and Yamaguchi, Masahiro and Miyamoto, Yusei and Hisatsune, Tatsuhiro}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Glial Fibrillary Acidic Protein;Research Support, Non-U.S. Gov't;Electrophysiology;Animals;In Vitro;Antigens, Differentiation;Patch-Clamp Techniques;Cell Count;Mice, Transgenic;Recombinant Fusion Proteins;Green Fluorescent Proteins;Sialic Acids;Intermediate Filament Proteins;Dentate Gyrus;Neurons;Mice;Neural Cell Adhesion Molecule L1;Immunohistochemistry;Bromodeoxyuridine;Luminescent Proteins;Nerve Tissue Proteins;Transgenes}, Medline = {22923783}, Month = {10}, Nlm_Id = {8102140}, Number = {28}, Organization = {Department of Integrated Biosciences, University of Tokyo, Kashiwa 277-8562, Japan.}, Pages = {9357-66}, Pii = {23/28/9357}, Pubmed = {14561863}, Title = {Two distinct subpopulations of nestin-positive cells in adult mouse dentate gyrus}, Uuid = {AD8B35FE-A3E5-11DA-AB00-000D9346EC2A}, Volume = {23}, Year = {2003}} @article{Fukuhara:2002, Author = {Fukuhara, S. and Tomita, S. and Nakatani, T. and Kishida, A. and Morisaki, T. and Yutani, C. and Kitamura, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0041-1345}, Journal = {Transplant Proc}, Keywords = {Transfection;Luminescent Proteins;Rats, Inbred Lew;Cell Transplantation;Bone Marrow Cells;Rats;Fluorescent Dyes;Heart Failure, Congestive;11 Glia;Mice, Transgenic;Bone Marrow Transplantation;Green Fluorescent Proteins;Disease Models, Animal;Genes, Reporter;Animals;Mice}, Medline = {22319876}, Month = {11}, Nlm_Id = {0243532}, Number = {7}, Organization = {Department of Pathology, National Cardiovascular Center, Osaka, Japan.}, Pages = {2718-21}, Pii = {S0041134502033869}, Pubmed = {12431585}, Title = {Comparison of cell labeling procedures for bone marrow cell transplantation to treat heart failure: long-term quantitative analysis}, Uuid = {B6157254-60B5-4C80-A04B-60CB657B603B}, Volume = {34}, Year = {2002}} @article{Fukumitsu:2002, Abstract = {In order to invent a screening system to check in vivo gene function and the efficiency of gene transfer mediated by a retroviral vector system, we established a novel packaging cell, PacC6/A8, that is transplantable to rat brains. The packaging cell is based on the gene of the neuropatogenic retrovirus, A8-V. For expression in the brain, a vector that expresses brain-derived neurotrophic factor (BDNF) tagged by c-Myc-His6 (LxA/bdmh) was constructed. After transfection of LxA/bdmh to PacC6/A8, a cloned cell line, PacC6/A8/bmh, was established. PacC6/A8/bmh cells stably produced pseudotyped retroviruses carrying LxA/bdmh. For a control, a retroviral vector that bears the gene that codes enhanced green fluorescent protein (EGFP) tagged by C-Mic-His6 was also created and used for the establishment of PacC6/A8/gfmh cells that produce pseudotyped retroviruses carrying LxA/gfmh. PacC6/A8/bmh and PacC6/A8/gfmh cells were injected to the brain of newborn rats. A tumor was formed in all the rats injected that did not exhibit any symptoms until 3-4 weeks after the injection. A histological study of the injected rats revealed that the transferred BDNF gene was expressed in the brain of rats injected with PacC6/A8/bmh cells, but not in rats with PacC6/A8/gfmh cells. Interestingly, many activated microglia had migrated into the tumor induced by PacC6/A8/bmh cells, and expressed a high amount of BDNF.}, Author = {Fukumitsu, Hidefumi and Takase-Yoden, Sayaka and Furukawa, Shoei and Nemoto, Kiyomitsu and Ikeda, Tomio and Watanabe, Rihito}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0963-6897}, Journal = {Cell Transplant}, Keywords = {Tumor Cells, Cultured;Luminescent Proteins;Virus Assembly;Cell Transplantation;Transduction, Genetic;Immunohistochemistry;Rats;Research Support, Non-U.S. Gov't;Retroviridae;11 Glia;Brain-Derived Neurotrophic Factor;Green Fluorescent Proteins;COS Cells;Brain;Animals;Gene Therapy;Genetic Vectors}, Medline = {22270116}, Nlm_Id = {9208854}, Number = {5}, Organization = {Institute of Life Science, Soka University, Hachioji, Tokyo, Japan.}, Pages = {459-64}, Pubmed = {12382674}, Title = {Implantation of BDNF-producing packaging cells into brain}, Uuid = {B3E1234E-5ECF-4F8B-9571-520D0490CEA5}, Volume = {11}, Year = {2002}} @article{Fukumitsu:2006, Abstract = {Lamina formation in the developing cerebral cortex requires precisely regulated generation and migration of the cortical progenitor cells. To test the possible involvement of brain-derived neurotrophic factor (BDNF) in the formation of the cortical lamina, we investigated the effects of BDNF protein and anti-BDNF antibody separately administered into the telencephalic ventricular space of 13.5-d-old mouse embryos. BDNF altered the position, gene-expression properties, and projections of neurons otherwise destined for layer IV to those of neurons for the deeper layers, V and VI, of the cerebral cortex, whereas anti-BDNF antibody changed some of those of neurons of upper layers II/III. Additional analysis revealed that BDNF altered the laminar fate of neurons only if their parent progenitor cells were exposed to it at approximately S-phase and that it hastened the timing of the withdrawal of their daughter neurons from the ventricular proliferating pool by accelerating the completion of S-phase, downregulation of the Pax6 (paired box gene 6) expression, an essential transcription factor for generation of the upper layer neurons, and interkinetic nuclear migration of cortical progenitors in the ventricular zone. These observations suggest that BDNF participates in the processes forming the neuronal laminas in the developing cerebral cortex. BDNF can therefore be counted as one of the key extrinsic factors that regulate the laminar fate of cortical neurons.}, Author = {Fukumitsu, Hidefumi and Ohtsuka, Masanari and Murai, Rina and Nakamura, Hiroyuki and Itoh, Kazuo and Furukawa, Shoei}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Pregnancy;24 Pubmed search results 2008;Cell Differentiation;research support, non-u.s. gov't;Gene Expression Regulation, Developmental;Female;Stem Cells;comparative study;Brain-Derived Neurotrophic Factor;Injections, Intraventricular;Animals;Cell Movement;Cerebral Cortex;Mice;Neurons}, Month = {12}, Nlm_Id = {8102140}, Number = {51}, Organization = {Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu 502-8585, Japan.}, Pages = {13218-30}, Pii = {26/51/13218}, Pubmed = {17182772}, Title = {Brain-derived neurotrophic factor participates in determination of neuronal laminar fate in the developing mouse cerebral cortex}, Uuid = {821067B4-1F20-45D1-859A-7282C15E045B}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4251-06.2006}} @article{Furukawa:2000, Abstract = {We are interested in the mechanisms of glial cell development in the vertebrate central nervous system. We have identified genes that can direct the formation of glia in the retina. rax, a homeobox gene, Hes1, a basic helix-loop-helix gene, and notch1, a transmembrane receptor gene, are expressed in retinal progenitor cells, downregulated in differentiated neurons, and expressed in Muller glia. Retroviral transduction of any of these genes resulted in expression of glial markers. In contrast, misexpression of a dominant-negative Hes1 gene reduced the number of glia. Cotransfection of rax with reporter constructs containing the Hes1 or notch1 regulatory regions led to the upregulation of reporter transcription. These data suggest a regulatory heirarchy that controls the formation of glia at the expense of neurons. 0896-6273 Journal Article}, Author = {Furukawa, T. and Mukherjee, S. and Bao, Z. Z. and Morrow, E. M. and Cepko, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Neuron}, Keywords = {G;Animals;Up-Regulation;Rats;Eye Proteins/*physiology;Retina/*cytology;Stem Cells/cytology;11 Glia;Genes, Dominant/physiology;Gene Expression/physiology;Support, Non-U.S. Gov't;3T3 Cells;Cell Division/physiology;Support, U.S. Gov't, P.H.S.;Homeodomain Proteins/genetics/*physiology;Mice;Animals, Newborn/physiology;Cell Differentiation/physiology;Biological Markers;Neuroglia/*cytology;Membrane Proteins/*physiology}, Number = {2}, Organization = {Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {383-94}, Title = {rax, Hes1, and notch1 promote the formation of Muller glia by postnatal retinal progenitor cells}, Uuid = {F13B7105-12CC-46DF-BE34-69B1826A985D}, Volume = {26}, Year = {2000}, url = {papers/Furukawa_Neuron2000}} @article{Furusho:2006, Abstract = {Cholinergic neurons, which express choline acetyltransferase (ChAT), are a major neuron subset generated in the basal forebrain. Areas presumed to be sites of origin of cholinergic neurons are roughly demarcated by expression of Olig2, a basic helix-loop-helix transcription factor, which includes the medial ganglionic eminence, septal area, and anterior entopeduncular/preoptic area. In the present study, we examined the involvement of Olig2 in cholinergic differentiation. When the Olig2-expressing cells at E12.5 were permanently modified to express the lacZ or EGFP gene by tamoxifen-induced Cre-mediated recombination, the cells marked by reporter gene expression were widely distributed in the basal forebrain by E18.5, some of which expressed neuronal markers. We showed that a small number of cells were double-positive for ChAT and X-gal or EGFP in almost all cases. In addition, the number of ChAT+ cells was reduced to 60\%in the Olig2 knockout mouse basal forebrain. No evidence of elevated apoptosis or reduced proliferation was observed in the knockout mouse forebrain. The present study provides the first direct evidence for involvement of the Olig2 gene in cholinergic differentiation in the basal forebrain.}, Author = {Furusho, and Ono, and Takebayashi, and Masahira, and Kagawa, and Ikeda, and Ikenaka,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {0372762}, Organization = {Department of Physiological Sciences, School of Life Science, The Graduate University for Advanced Studies (SOKENDAI), Okazaki, Aichi 444-8787, Japan; Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan.}, Pii = {S0012-1606(06)00074-1}, Pubmed = {16537079}, Title = {Involvement of the Olig2 transcription factor in cholinergic neuron development of the basal forebrain}, Uuid = {51909473-676C-4467-A989-5C435BA3BA3E}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2006.01.031}} @article{Furuya:2003, Abstract = {Chimeric mice stably reconstituted with bone marrow cells represent a good model for analysis of the mechanism of bone marrow cell infiltration in the brain. However, in preparing chimeric mice, irradiation of the recipient mice is necessary to kill their own bone marrow before transplantation, which induces gliosis and inflammatory response by activation of astrocytes and microglia in the brain. Here, we determined the most suitable dose of irradiation associated with the least brain damage before transplantation for reconstitution of chimeric mice, using FACS analysis. Our mouse model of 10 Gy body/5 Gy head irradiation should be useful for investigating the mechanism(s) of microglial activation in various neurological disorders such as stroke, Alzheimer's disease and Parkinson's disease.}, Author = {Furuya, Tsuyoshi and Tanaka, Ryota and Urabe, Takao and Hayakawa, Jun and Migita, Makoto and Shimada, Takashi and Mizuno, Yoshikuni and Mochizuki, Hideki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Animals;Head;Macrophages;Bone Marrow Transplantation;Comparative Study;Nervous System Diseases;Mice, Transgenic;Substantia Nigra;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Disease Models, Animal;Radiation Chimera;Olfactory Bulb;Bone Marrow;Bone Marrow Cells;Pia Mater;Choroid Plexus;Flow Cytometry;Mice;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22544995}, Month = {3}, Nlm_Id = {9100935}, Number = {4}, Organization = {Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.}, Pages = {629-31}, Pubmed = {12657900}, Title = {Establishment of modified chimeric mice using GFP bone marrow as a model for neurological disorders}, Uuid = {4564C259-78AF-4623-9CCE-2991A2BDEB23}, Volume = {14}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1097/01.wnr.0000063507.18654.d8}} @article{Gabel:2001, Abstract = {Focal developmental abnormalities in neocortex, including ectopic collections of neurons in layer I (ectopias), have been associated with behavioral and neurological deficits. In this study, we used infrared differential interference contrast microscopy and whole cell patch-clamp to complete the first characterization of neurons within and surrounding neocortical ectopias. Current-clamp recordings revealed that neurons within ectopias display multiple types of action potential firing patterns, and biocytin labeling indicated that approximately 20\%of the cells in neocortical ectopias can be classified as nonpyramidal cells and the rest as atypically oriented pyramidal cells. All cells had spontaneous excitatory (glutamatergic) and inhibitory (GABAergic) postsynaptic currents. Exhibitory postsynaptic currents consisted of both N-methyl-D-aspartate (NMDA) receptor-mediated and AMPA/kainate (A/K) receptor-mediated currents. The NMDA receptor-mediated component had decay time constants of 15.35 +/- 2.2 (SE) ms, while the A/K component had faster decay kinetics of 7.6 +/- 1.7 ms at -20 mV. GABA(A) receptor-mediated synaptic currents in ectopic cells reversed at potentials near the Cl- equilibrium potential and had decay kinetics of 16.65 +/- 1.3 ms at 0 mV. Furthermore we show that cells within ectopias receive direct excitatory and inhibitory input from adjacent normatopic cortex and can display a form of epileptiform activity.}, Author = {Gabel, L. A. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {gamma-Aminobutyric Acid;Electrophysiology;Animals;Synapses;Glutamic Acid;Afferent Pathways;Neocortex;Mice, Inbred NZB;Epilepsy;Female;21 Dysplasia-heterotopia;Brain Diseases;Male;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred Strains;21 Neurophysiology;Neurons;Mice;24 Pubmed search results 2008;Neural Inhibition;Choristoma}, Medline = {21104035}, Month = {2}, Nlm_Id = {0375404}, Number = {2}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA.}, Pages = {495-505}, Pubmed = {11160488}, Title = {Electrophysiological and morphological characterization of neurons within neocortical ectopias}, Uuid = {DAF4B1A7-AFA3-4A48-AB70-B15823902584}, Volume = {85}, Year = {2001}, url = {papers/Gabel_JNeurophysiol2001.pdf}} @article{Gabel:2002, Abstract = {Cortical dysplasias are associated with both epilepsy and cognitive impairments in humans. Similarly, several animal models of cortical dysplasia show that dysplasia causes increased seizure susceptibility and behavioral deficits in vivo and increased levels of excitability in vitro. As most current animal models involve either global disruptions in cortical architecture or the induction of lesions, it is not yet clear whether small spontaneous neocortical malformations are also associated with increased excitability or seizure susceptibility. Small groups of displaced neurons in layer I of the neocortex, ectopias, have been identified in patients with cognitive impairments, and similar malformations occur sporadically in some inbred lines of mice where they are associated with behavioral and sensory-processing deficits. In a previous study, we characterized the physiology of cells within neocortical ectopias, in one of the inbred lines (NXSM-D/Ei) and showed that the presence of multiple ectopias is associated with the generation of spontaneous epileptiform activity in slices. In this study, we use extracellular recordings from brain slices to show that even single-layer I ectopias are associated with higher excitability. Specifically, slices that contain single ectopias display epileptiform activity at significantly lower concentrations of the GABA(A) receptor antagonist bicuculline than do slices without ectopias (either from opposite hemispheres or animals without ectopias). Moreover, because removal of ectopias from slices does not restore normal excitability, enhanced excitability is not generated within the ectopia. Finally, we show that in vivo, mice with ectopias are more sensitive to the convulsant pentylenetetrazole than are mice without ectopias. Together these results suggest that alterations in cortical hemispheres containing focal layer I malformations increase cortical excitability and that even moderately small spontaneous cortical dysplasias are associated with increased excitability in vitro and in vivo.}, Author = {Gabel, Lisa A. and LoTurco, Joseph J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Epilepsy;Disease Susceptibility;21 Epilepsy;21 Dysplasia-heterotopia;21 Neurophysiology;Mice, Inbred NZB;Female;Pyramidal Cells;Research Support, U.S. Gov't, P.H.S.;Neocortex;Electrophysiology;Organ Culture Techniques;Animals;Disease Models, Animal;Male;Mice;24 Pubmed search results 2008}, Medline = {21972947}, Month = {5}, Nlm_Id = {0375404}, Number = {5}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA.}, Pages = {2471-9}, Pubmed = {11976384}, Title = {Layer I ectopias and increased excitability in murine neocortex}, Uuid = {DC9DD259-53F8-4C5F-8D71-AD4E7CB39E86}, Volume = {87}, Year = {2002}, url = {papers/Gabel_JNeurophysiol2002.pdf}} @article{Gage:1995, Abstract = {The nervous system of adult mammals, unlike the rest of the organs in the body, has been considered unique in its apparent inability to replace neurons following injury. However, in certain regions of the brain, neurogenesis occurs postnatally and continues through adulthood. The nature, fate, and longevity of cells undergoing proliferation within the CNS are unknown. These cells are increasingly becoming the focus of intense scrutiny; this is a recent development that has led to considerable controversy over the appropriate terminology to describe neural cells as they pass through different stages of proliferation, migration, and differentiation. Continuing studies detailing the properties of mitotic populations in the adult CNS will provide a better understanding of the nature of these cells during their development and should lead to a more consistent nomenclature. Studies of neural precursors isolated from the embryonic brain have indicated that many subgroups of cells undergo mitosis and subsequent differentiation into neurons and glia in vitro. A number of substances, such as growth factors and substrate molecules, are essential for these processes and also for lineage restriction and fate determination of these cells. Recent studies have shown that cells with proliferative capabilities can also be isolated from the adult brain. The nature of these cells is unknown, but there is evidence that both multipotent cells (stem cells) and lineage-restricted cells (neuroblasts or glioblasts) are resident within the mature CNS and that they can be maintained and induced to divide and differentiate in response to many of the same factors that influence their embryonic counterparts. Presently, it is unclear how many potentially quiescent precursor cells exist in the adult brain or what combination of growth factors and substrate molecules is involved in the proliferation and differentiation of these cells. Some of these questions are currently being addressed by using immortalized neural precursors or growth factor-expanded populations of primary precursors to model precursor responsiveness to environmental manipulations. Because in vitro culture conditions are unlikely to provide all of the factors necessary for inducing the proliferation and differentiation of neural precursors, recent studies have explored the properties of well-characterized precursor populations after implantation back into specific regions of the developing or adult CNS. These studies have highlighted the importance of the microenvironment in precursor differentiation and further suggested that precursor plasticity is a characteristic that is probably common to neural precursors throughout the CNS.(ABSTRACT TRUNCATED AT 400 WORDS) Using Smart Source Parsing}, Author = {Gage, F. H. and Ray, J. and Fisher, L. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Annu Rev Neurosci}, Keywords = {BB abstr;02 Adult neurogenesis migration;Brain Tissue Transplantation;Adult;03 Adult neurogenesis progenitor source;Human;Stem Cells/*cytology/transplantation;Animal;Neuronal Plasticity/*physiology;Brain/*cytology/growth &development;Cell Separation;Fetal Tissue Transplantation}, Organization = {Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92093-0627, USA.}, Pages = {159-92}, Title = {Isolation, characterization, and use of stem cells from the CNS}, Uuid = {B2799C98-9006-4907-AE3F-8F003E16490D}, Volume = {18}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7605059}} @article{Gage:1998, Abstract = {Neurogenesis persists in the adult dentate gyrus of rodents throughout the life of the organism. The factors regulating proliferation, survival, migration, and differentiation of neuronal progenitors are now being elucidated. Cells from the adult hippocampus can be propagated, cloned in vitro, and induced to differentiate into neurons and glial cells. Cells cultured from the adult rodent hippocampus can be genetically marked and transplanted back to the adult brain, where they survive and differentiate into mature neurons and glial cells. Although multipotent stem cells exist in the adult rodent dentate gyrus, their biological significance remains elusive.}, Author = {Gage, F. H. and Kempermann, G. and Palmer, T. D. and Peterson, D. A. and Ray, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurobiol}, Keywords = {02 Adult neurogenesis migration;Hippocampus/cytology/embryology/growth &development;Stem Cells/*physiology/transplantation;Dentate Gyrus/*cytology;Human;Spinal Cord/cytology;03 Adult neurogenesis progenitor source;Animal;Support, U.S. Gov't, P.H.S.;BB;Neurons/*physiology/transplantation;Support, Non-U.S. Gov't;Brain/embryology/physiology;Fetal Development/physiology}, Number = {2}, Organization = {Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA.}, Pages = {249-66.}, Title = {Multipotent progenitor cells in the adult dentate gyrus}, Uuid = {201358F4-F598-45E0-AC16-CE2C56AA880C}, Volume = {36}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9712308}} @article{Gage:2002, Author = {Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {J Neurosci}, Keywords = {Brain/*cytology/growth &development/physiology;01 Adult neurogenesis general;Cell Division/physiology;Neuronal Plasticity/physiology;Neurons/*cytology/physiology;Human;Models, Neurological;A both;Animal;Cell Differentiation/physiology;Stem Cells/cytology/physiology}, Number = {3}, Organization = {Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA. gage\@salk.edu}, Pages = {612-3.}, Title = {Neurogenesis in the adult brain}, Uuid = {42746EF9-0CA5-4997-A654-BD0E1CEC06D0}, Volume = {22}, Year = {2002}, url = {papers/Gage_JNeurosci2002.pdf}} @article{Gage:1995a, Abstract = {The dentate gyrus of the hippocampus is one of the few areas of the adult brain that undergoes neurogenesis. In the present study, cells capable of proliferation and neurogenesis were isolated and cultured from the adult rat hippocampus. In defined medium containing basic fibroblast growth factor (FGF-2), cells can survive, proliferate, and express neuronal and glial markers. Cells have been maintained in culture for 1 year through multiple passages. These cultured adult cells were labeled in vitro with bromodeoxyuridine and adenovirus expressing beta-galactosidase and were transplanted to the adult rat hippocampus. Surviving cells were evident through 3 months postimplantation with no evidence of tumor formation. Within 2 months postgrafting, labeled cells were found in the dentate gyrus, where they differentiated into neurons only in the intact region of the granule cell layer. Our results indicate that FGF-2 responsive progenitors can be isolated from the adult hippocampus and that these cells retain the capacity to generate mature neurons when grafted into the adult rat brain.}, Author = {Gage, F. H. and Coates, P. W. and Palmer, T. D. and Kuhn, H. G. and Fisher, L. J. and Suhonen, J. O. and Peterson, D. A. and Suhr, S. T. and Ray, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Survival;10 Development;Cell Differentiation;Fibroblast Growth Factor, Basic/pharmacology;10 Hippocampus;Rats;Fluorescent Antibody Technique;Hippocampus/*cytology/*surgery;Female;Tissue Culture/*methods;02 Adult neurogenesis migration;Animal;BB abstr;03 Adult neurogenesis progenitor source;Rats, Inbred F344;Stem Cells/drug effects/*transplantation/ultrastructure;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;*Brain Tissue Transplantation;Biological Markers;Neurons/drug effects/*transplantation/ultrastructure}, Number = {25}, Organization = {Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.}, Pages = {11879-83.}, Title = {Survival and differentiation of adult neuronal progenitor cells transplanted to the adult brain}, Uuid = {F21C7EC2-6875-11DA-A4B6-000D9346EC2A}, Volume = {92}, Year = {1995}, url = {papers/Gage_ProcNatlAcadSciUSA1995.pdf}} @article{Gage:2000, Abstract = {Neural stem cells exist not only in the developing mammalian nervous system but also in the adult nervous system of all mammalian organisms, including humans. Neural stem cells can also be derived from more primitive embryonic stem cells. The location of the adult stem cells and the brain regions to which their progeny migrate in order to differentiate remain unresolved, although the number of viable locations is limited in the adult. The mechanisms that regulate endogenous stem cells are poorly understood. Potential uses of stem cells in repair include transplantation to repair missing cells and the activation of endogenous cells to provide "self-repair. "Before the full potential of neural stem cells can be realized, we need to learn what controls their proliferation, as well as the various pathways of differentiation available to their daughter cells.}, Author = {Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Science}, Keywords = {02 Adult neurogenesis migration;Cell Differentiation;Embryo/cytology;Spinal Cord/cytology/embryology;Human;Neurons/*cytology/physiology;Brain/*cytology/embryology;Cell Division;Animal;Cell Death;Support, U.S. Gov't, P.H.S.;*Stem Cells/cytology/physiology/transplantation;Support, Non-U.S. Gov't;B-22;Cell Separation;Cell Movement}, Number = {5457}, Organization = {The Salk Institute, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. gage\@salk.edu.}, Pages = {1433-8.}, Title = {Mammalian neural stem cells}, Uuid = {68F252B8-D58B-4B84-AAD6-40DF4E8D3081}, Volume = {287}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10688783}} @article{Gaiano:2000, Abstract = {In vertebrates, Notch signaling is generally thought to inhibit neural differentiation. However, whether Notch can also promote specific early cell fates in this context is unknown. We introduced activated Notch1 (NIC) into the mouse forebrain, before the onset of neurogenesis, using a retroviral vector and ultrasound imaging. During embryogenesis, NIC-infected cells became radial glia, the first specialized cell type evident in the forebrain. Thus, rather than simply inhibiting differentiation, Notch1 signaling promoted the acquisition of an early cellular phenotype. Postnatally, many NIC-infected cells became periventricular astrocytes, cells previously shown to be neural stem cells in the adult. These results suggest that Notch1 promotes radial glial identity during embryogenesis, and that radial glia may be lineally related to stem cells in the adult nervous system. 0896-6273 Journal Article}, Author = {Gaiano, N. and Nye, J. S. and Fishell, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Neuron}, Keywords = {Neuroglia/*physiology;10 Development;Phenotype;Membrane Proteins/metabolism/*physiology;Retroviridae/metabolism;Animals, Newborn/physiology;F;Support, U.S. Gov't, P.H.S.;Signal Transduction/*physiology;Retroviridae Infections/pathology;Support, Non-U.S. Gov't;Animals;Mice;Prosencephalon/*cytology/*physiology}, Number = {2}, Organization = {Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York 10016, USA.}, Pages = {395-404}, Pubmed = {10839358}, Title = {Radial glial identity is promoted by Notch1 signaling in the murine forebrain}, Uuid = {88917F31-915C-423B-BC06-33CD6D9439F8}, Volume = {26}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10839358}} @article{Gal:2006, Abstract = {The proliferative ventricular zone (VZ) is the main source of projection neurons for the overlying cerebral neocortex. The number and diversity of neocortical neurons is determined, in part, by factors controlling the proliferation and specification of VZ cells during embryonic development. We used a variety of methods, including in utero electroporation with specific cellular markers, computer-assisted serial EM cell reconstruction, and time-lapse multiphoton imaging to characterize the molecular and morphological characteristics of the VZ constituents and to capture their behavior during cell division. Our analyses reveal at least two types of dividing cells in the VZ: (1) radial glial cells (RGCs) that span the entire neocortical wall and maintain contact both at the ventricular and pial surfaces throughout mitotic division, and (2) short neural precursors (SNPs) that possess a ventricular endfoot and a basal process of variable length that is retracted during mitotic division. These two precursor cell classes are present concomitantly in the VZ, but their relative number changes over the course of cortical neurogenesis. Moreover, the SNPs are morphologically, ultrastructurally and molecularly distinct from dividing RGCs. For example, SNPs are marked by their preferential expression of the tubulin alpha-1 promoter whereas RGCs instead express the glutamate-aspartate transporter and brain lipid binding protein promoters. In contrast to recent studies that suggest that RGCs are the sole type of VZ precursor, the present study indicates that the VZ in murine dorsal telencephalon is similar to that in human and nonhuman primates, because it contains multiple types of neuronal precursors.}, Author = {Gal, Jonathan S. and Morozov, Yury M. and Ayoub, Albert E. and Chatterjee, Mitali and Rakic, Pasko and Haydar, Tarik F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Embryo;10 Development;Research Support, Non-U.S. Gov't;Comparative Study;Cell Proliferation;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Neocortex;Female;Research Support, N.I.H., Extramural;Pregnancy;Animals;Mice;24 Pubmed search results 2008;Humans;Neurons}, Month = {1}, Nlm_Id = {8102140}, Number = {3}, Organization = {Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA.}, Pages = {1045-56}, Pii = {26/3/1045}, Pubmed = {16421324}, Title = {Molecular and morphological heterogeneity of neural precursors in the mouse neocortical proliferative zones}, Uuid = {BCADD2EC-7480-4326-A2F5-1CB88B4B9F60}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4499-05.2006}} @article{Galaburda:1985, Abstract = {We report the neuroanatomical findings in 4 consecutively studied brains of men with developmental dyslexia. The patients, who ranged in age between 14 and 32 years, were diagnosed as dyslexic during life. Nonrighthandedness and several autoimmune and atopic illnesses were present in the personal and family histories. All brains showed developmental anomalies of the cerebral cortex. These consisted of neuronal ectopias and architectonic dysplasias located mainly in perisylvian regions and affecting predominantly the left hemisphere. Furthermore, all brains showed a deviation from the standard pattern of cerebral asymmetry characterized by symmetry of the planum temporale. The neuroanatomical findings in these 4 patients are discussed with reference to developmental cortical anomalies, cerebral asymmetries, reorganization of the brain after early lesions, and the association between learning disorders, left handedness, and diseases of the immune system.}, Author = {Galaburda, A. M. and Sherman, G. F. and Rosen, G. D. and Aboitiz, F. and Geschwind, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-09-25 12:31:24 +0000}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {Dominance, Cerebral;10 Development;research support, non-u.s. gov't;Adolescent;Dyslexia;Immune System Diseases;10 genetics malformation;Child;research support, u.s. gov't, p.h.s.;Humans;Male;Cerebral Cortex;case reports; cerebral cortex; hemipshere; Grants; forelimb}, Month = {8}, Nlm_Id = {7707449}, Number = {2}, Pages = {222-33}, Pubmed = {4037763}, Title = {Developmental dyslexia: four consecutive patients with cortical anomalies}, Uuid = {1803FFB4-36AB-4D78-B399-ACEC46A0830C}, Volume = {18}, Year = {1985}, url = {papers/Galaburda_AnnNeurol1985.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.410180210}} @article{Galaburda:2006, Abstract = {All four genes thus far linked to developmental dyslexia participate in brain development, and abnormalities in brain development are increasingly reported in dyslexia. Comparable abnormalities induced in young rodent brains cause auditory and cognitive deficits, underscoring the potential relevance of these brain changes to dyslexia. Our perspective on dyslexia is that some of the brain changes cause phonological processing abnormalities as well as auditory processing abnormalities; the latter, we speculate, resolve in a proportion of individuals during development, but contribute early on to the phonological disorder in dyslexia. Thus, we propose a tentative pathway between a genetic effect, developmental brain changes, and perceptual and cognitive deficits associated with dyslexia.}, Author = {Galaburda, Albert M. and LoTurco, Joseph and Ramus, Franck and Fitch, R. Holly and Rosen, Glenn D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Cognition Disorders;research support, n.i.h., extramural ;Models, Molecular;research support, non-u.s. gov't ;Dyslexia;Behavior;Animals;Disease Models, Animal;Humans;review;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {Department of Neurology, Division of Behavioral Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts 02215, USA. agalabur\@bidmc.harvard.edu}, Pages = {1213-7}, Pii = {nn1772}, Pubmed = {17001339}, Title = {From genes to behavior in developmental dyslexia}, Uuid = {2B06D6E0-6268-41A5-9D06-746A813891EB}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1772}} @article{Galaburda:1993, Abstract = {This article reviews the known neuroanatomic and neuropathologic bases of developmental dyslexia in the context of some of the functional deficits exhibited by affected individuals. Observations from autopsy brains and experimental animal models disclose problems with cerebral asymmetry, focal developmental disorders affecting the cerebral cortex, and abnormalities in the magnocellular pathway of the visual system.}, Author = {Galaburda, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0733-8619}, Journal = {Neurol Clin}, Keywords = {21 Epilepsy;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;Dyslexia;Animals;Brain;Cerebral Cortex;review;Humans}, Medline = {93180712}, Month = {2}, Nlm_Id = {8219232}, Number = {1}, Organization = {Department of Neurology, Harvard Medical School, Boston, Massachusetts.}, Pages = {161-73}, Pubmed = {8441368}, Title = {Neuroanatomic basis of developmental dyslexia}, Uuid = {516D1990-D0E3-44B2-A46B-B6F3358E66B7}, Volume = {11}, Year = {1993}} @article{Galaburda:2003, Abstract = {This review of developmental disorders of vision focuses on only a few of the many disorders that disrupt visual development. Given the enormity of the human visual system in the primate brain and complexity of visual development, however, there are likely hundreds or thousands of types of disorders affecting high-level vision. The rapid progress seen in developmental dyslexia and WMS demonstrates the possibilities and difficulties inherent in researching such disorders, and the authors hope that similar progress will be made for congenital prosopagnosia and other disorders in the near future.}, Author = {Galaburda, Albert M. and Duchaine, Bradley C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0733-8619}, Journal = {Neurol Clin}, Keywords = {Williams Syndrome;24 Pubmed search results 2008;Brain Ischemia;Magnetic Resonance Imaging;Visual Perception;21 Neurophysiology;Perceptual Disorders;Dyslexia;Developmental Disabilities;Child;research support, u.s. gov't, p.h.s.;Humans;Brain;Nerve Net;review;Prosopagnosia}, Month = {8}, Nlm_Id = {8219232}, Number = {3}, Organization = {Division of Behavioral Neurology, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA. agalabur\@caregroup.harvard.edu}, Pages = {687-707}, Pubmed = {13677818}, Title = {Developmental disorders of vision}, Uuid = {724AB740-07B8-4CCE-8FBC-C2D462B14C13}, Volume = {21}, Year = {2003}, url = {papers/Galaburda_NeurolClin2003.pdf}} @article{Galceran:2000, Abstract = {Lef1 and other genes of the LEF1/TCF family of transcription factors are nuclear mediators of Wnt signaling. Here we examine the expression pattern and functional importance of Lef1 in the developing forebrain of the mouse. Lef1 is expressed in the developing hippocampus, and LEF1-deficient embryos lack dentate gyrus granule cells but contain glial cells and interneurons in the region of the dentate gyrus. In mouse embryos homozygous for a Lef1-lacZ fusion gene, which encodes a protein that is not only deficient in DNA binding but also interferes with (beta)-catenin-mediated transcriptional activation by other LEF1/TCF proteins, the entire hippocampus including the CA fields is missing. Thus, LEF1 regulates the generation of dentate gyrus granule cells, and together with other LEF1/TCF proteins, the development of the hippocampus.}, Author = {Galceran, J. and Miyashita-Lin, E. M. and Devaney, E. and Rubenstein, J. L. and Grosschedl, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Trans-Activation (Genetics);Transcription Factors;beta-Galactosidase;Animals;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Transfection;Recombinant Proteins;Apoptosis;Mice, Transgenic;Hippocampus;Embryonic and Fetal Development;Prosencephalon;Research Support, U.S. Gov't, P.H.S.;Mice, Knockout;Tumor Cells, Cultured;Dentate Gyrus;Homozygote;Neuroglia;Mice;Interneurons;Research Support, Non-U.S. Gov't}, Medline = {20098486}, Month = {2}, Nlm_Id = {8701744}, Number = {3}, Organization = {Howard Hughes Medical Institute, Department of Microbiology, University of California, San Francisco, CA 94143, USA.}, Pages = {469-82}, Pubmed = {10631168}, Title = {Hippocampus development and generation of dentate gyrus granule cells is regulated by LEF1}, Uuid = {E08412AA-7113-11DA-9A4D-000D9346EC2A}, Volume = {127}, Year = {2000}, url = {papers/Galceran_Development2000.pdf}} @article{Galea:2005, Abstract = {Perivascular macrophages are believed to have a significant role in inflammation in the central nervous system (CNS). They express a number of different receptors that point toward functions in both innate immunity, through pathogen-associated molecular pattern recognition, phagocytosis, and cytokine responsiveness, and acquired immunity, through antigen presentation and co-stimulation. We are interested in the receptors that are differentially expressed by perivascular macrophages and microglia in both the normal CNS as well as in neuroinflammation and neurodegeneration. In this article we report the use of a well-characterized monoclonal antibody, 5D3, to localize the expression of the mannose receptor to perivascular macrophages in the normal CNS and in various models of brain pathology. Mannose receptor expression was limited to perivascular, meningeal, and choroid plexus macrophages in normal, inflamed, injured, and diseased CNS. In particular, activated microglia and invading hematogenous leukocytes were mannose receptor negative while expressing the F4/80 antigen, macrosialin (CD68), FcRII (CD32), scavenger receptor (CD204), and CR3 (CD11b/CD18). Since the perivascular macrophages expressing the mannose receptor are known to be the only constitutively phagocytic cells in the normal CNS, we injected clodronate-loaded liposomes intracerebroventricularly in control mice to deplete these cells. In these mice, there was no detectable mannose receptor expression in perivascular spaces after immunocytochemistry with the 5D3 monoclonal antibody. This finding underlines the value of the monoclonal antibody 5D3 as a tool to study murine perivascular macrophages selectively. Mannose receptor expression by macrophages located at blood-brain (perivascular), brain-cerebrospinal fluid (CSF) (meningeal), and CSF-blood (choroid plexus) interfaces supports a functional role of these cells in responding to external stimuli such as infection.}, Author = {Galea, Ian and Palin, Karine and Newman, Tracey A. and Van Rooijen, Nico and Perry, V. Hugh and Boche, Delphine}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Research Support, Non-U.S. Gov't;Receptors, Cell Surface;Blood-Brain Barrier;Neurodegenerative Diseases;Female;Gene Expression Regulation;Lectins, C-Type;Mice, Inbred C57BL;11 Glia;Mannose-Binding Lectins;Macrophages;Mice;Brain;Animals}, Month = {2}, Nlm_Id = {8806785}, Number = {3}, Organization = {CNS Inflammation Group, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK. i.galea\@soton.ac.uk}, Pages = {375-84}, Pubmed = {15538754}, Title = {Mannose receptor expression specifically reveals perivascular macrophages in normal, injured, and diseased mouse brain}, Uuid = {109E3A92-8A02-4CA3-A9DB-F3DF2EDADA8E}, Volume = {49}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20124}} @article{Galiano:2001, Abstract = {Nerve injury triggers numerous changes in the injured neurons and surrounding non-neuronal cells. Of particular interest are molecular signals that play a role in the overall orchestration of this multifaceted cellular response. Here we investigated the function of interleukin-6 (IL6), a multifunctional neurotrophin and cytokine rapidly expressed in the injured nervous system, using the facial axotomy model in IL6-deficient mice and wild-type controls. Transgenic deletion of IL6 caused a massive decrease in the recruitment of CD3-positive T-lymphocytes and early microglial activation during the first 4 days after injury in the axotomized facial nucleus. This was accompanied by a more moderate reduction in peripheral regeneration at day 4, lymphocyte recruitment (day 14) and enhanced perikaryal sprouting (day 14). Motoneuron cell death, phagocytosis by microglial cells and recruitment of granulocytes and macrophages into injured peripheral nerve were not affected. In summary, IL6 lead to a variety of effects on the cellular response to neural trauma. However, the particularly strong actions on lymphocytes and microglia suggest that this cytokine plays a central role in the initiation of immune surveillance in the injured central nervous system.}, Author = {Galiano, M. and Liu, Z. Q. and Kalla, R. and Bohatschek, M. and Koppius, A. and Gschwendtner, A. and Xu, S. and Werner, A. and Kloss, C. U. and Jones, L. L. and Bluethmann, H. and Raivich, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Cell Survival;Animals;Fluorescent Antibody Technique;Microglia;Lymphocyte Activation;Not relevant;11 Glia;Time Factors;Disease Models, Animal;Nerve Regeneration;Facial Nerve Injuries;Support, Non-U.S. Gov't;Mice, Knockout;Motor Neurons;Gliosis;Mice;Interleukin-6;Retrograde Degeneration;Nerve Tissue Proteins;Growth Cones;Facial Nerve}, Medline = {21437552}, Month = {7}, Nlm_Id = {8918110}, Number = {2}, Organization = {Department of Neuromorphology, Max-Planck Institute for Neurobiology, Am Klopferspitz 18A, D-82152 Martinsried, Germany.}, Pages = {327-41}, Pii = {ejn1647}, Pubmed = {11553283}, Title = {Interleukin-6 (IL6) and cellular response to facial nerve injury: effects on lymphocyte recruitment, early microglial activation and axonal outgrowth in IL6-deficient mice}, Uuid = {03B51EF1-360A-40DE-94DC-FAC4F961597A}, Volume = {14}, Year = {2001}} @article{Gallay:1997, Abstract = {The karyophilic properties of the HIV-1 nucleoprotein complex facilitate infection of nondividing cells such as macrophages and quiescent T lymphocytes, and allow the in vivo delivery of transgenes by HIV-derived retroviral vectors into terminally differentiated cells such as neurons. Although the viral matrix (MA) and Vpr proteins have previously been shown to play important roles in this process, we demonstrate here that integrase, the enzyme responsible for mediating the integration of the viral genome in the host cell chromosome, can suffice to connect the HIV-1 preintegration complex with the cell nuclear import machinery. This novel function of integrase reflects the recognition of an atypical bipartite nuclear localization signal by the importin/karyopherin pathway.}, Author = {Gallay, P. and Hope, T. and Chin, D. and Trono, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Differentiation;Research Support, Non-U.S. Gov't;HIV Infections;HIV-1;Integrases;Virus Replication;Research Support, U.S. Gov't, P.H.S.;Signal Transduction;Cell Line;Cell Division;Karyopherins;Nuclear Proteins;15 Retrovirus mechanism;Humans;24 Pubmed search results 2008;Neurons}, Medline = {97420768}, Month = {9}, Nlm_Id = {7505876}, Number = {18}, Organization = {The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037-1099, USA.}, Pages = {9825-30}, Pubmed = {9275210}, Title = {HIV-1 infection of nondividing cells through the recognition of integrase by the importin/karyopherin pathway}, Uuid = {197877FC-68FF-472E-B6BD-149FC9B38081}, Volume = {94}, Year = {1997}} @article{Galle:1994, Abstract = {BACKGROUND/AIMS: Studies on the interaction of hepatitis B virus (HBV) with its host cell require a suitable tissue culture system. This study used primary adult hepatocytes from healthy human liver tissue to establish productive infection in vitro. METHODS: Hepatocytes were inoculated overnight with HBV. Production of viral proteins was assessed by radioimmunoassay and by [35S]methionine labeling, and production of viral DNA was assessed by Southern blotting and endogenous polymerase assay. RESULTS: Secretion of high levels of hepatitis B surface antigen (HBsAg) and low levels of hepatitis B virus e antigen (HBeAg) into the medium was detectable 6 days after infection and reached maximum values after 12 days. Metabolic labeling showed production of viral proteins to be a result of de novo synthesis. The appearance of single-stranded HBV DNA in the cytoplasm of infected cells, typically present in immature cores, indicated viral replication. HBV DNA containing particles possessing an active viral DNA polymerase could be immunoprecipitated from the medium 12 days after infection. An antiserum specific for the preS1 region of the viral envelope was capable to block infection. Presence of dimethyl sulfoxide in the medium greatly improved the yield of viral proteins. CONCLUSIONS: Primary adult human liver cells are competent for infection with HBV. 0016-5085 Journal Article}, Author = {Galle, P. R. and Hagelstein, J. and Kommerell, B. and Volkmann, M. and Schranz, P. and Zentgraf, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Gastroenterology}, Keywords = {Human;Animals;Cells, Cultured;Fluorescent Antibody Technique;Virion/metabolism;DNA, Viral/metabolism;Disease Susceptibility;08 Aberrant cell cycle;EE, DMSO, abstr;Dimethyl Sulfoxide/pharmacology;Viral Proteins/biosynthesis;Support, Non-U.S. Gov't;Immune Sera/pharmacology;Methionine/metabolism;Fetal Blood;Cattle/embryology;Hepatitis B/*metabolism/pathology/prevention &control;Radioimmunoassay;Culture Media;Liver/*metabolism/pathology}, Number = {3}, Organization = {Department of Internal Medicine, University of Heidelberg, Germany.}, Pages = {664-73}, Pubmed = {8119538}, Title = {In vitro experimental infection of primary human hepatocytes with hepatitis B virus}, Uuid = {8F3D3E38-6561-4832-8E37-24CD7E7A33AE}, Volume = {106}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8119538}} @article{Gallo:1971, Author = {Gallo, R. C. and Sarin, P. S. and Allen, P. T. and Newton, W. A. and Priori, E. S. and Bowen, J. M. and Dmochowski, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0090-0028}, Journal = {Nat New Biol}, Keywords = {Oncogenic Viruses;RNA Viruses;Humans;Mycoplasma;Guanine Nucleotides;Centrifugation, Density Gradient;15 Retrovirus mechanism;Neoplasms;Male;Adenosine Triphosphate;Magnesium;DNA Nucleotidyltransferases;Cytosine Nucleotides;24 Pubmed search results 2008;Burkitt Lymphoma;Autoradiography;15 ERVs retroelements;Tritium;Microscopy, Electron}, Medline = {71291919}, Month = {8}, Nlm_Id = {0410463}, Number = {31}, Pages = {140-2}, Pubmed = {5285568}, Title = {Reverse transcriptase in type C virus particles of human origin}, Uuid = {8DFFAA0C-4328-11DB-A5D2-000D9346EC2A}, Volume = {232}, Year = {1971}} @article{Galvez:2005, Abstract = {The Fragile-X mental retardation syndrome is the leading form of inherited mental retardation. Dendritic analysis in a mouse model (FraX) found abnormal pruning in somatosensory cortex. To further characterize dendritic abnormalities and assess their occurrence in other brain regions, we examined mitral cells in FraX mice olfactory bulbs. FraX mice exhibited dendritic abnormalities consistent with somatosensory cortex, suggesting that deficient pruning is found in multiple brain regions.}, Author = {Galvez, and Smith, and Greenough,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {10 Development;10 Structural plasticity}, Month = {5}, Nlm_Id = {8908639}, Organization = {Neuroscience Program, University of Illinois, Urbana, IL 61801, USA; Beckman Institute, University of Illinois, 405 N Mathews, Urbana, IL 61801, USA.}, Pii = {S0165-3806(05)00107-0}, Pubmed = {15878626}, Title = {Olfactory bulb mitral cell dendritic pruning abnormalities in a mouse model of the Fragile-X mental retardation syndrome: Further support for FMRP's involvement in dendritic development}, Uuid = {0F1C4B6E-2BF1-46C0-9180-74E3B79D9E6B}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devbrainres.2005.03.010}} @article{Gan:2003, Abstract = {Naturally occurring rearrangements of synaptic terminals are common in the nervous systems of young mammals, but little is known about their incidence in adults. Using transgenic mice that express yellow fluorescent protein (YFP) in axons, we repeatedly imaged nerve terminals in the parasympathetic submandibular ganglion. We found that the pattern of synaptic branches underwent significant rearrangements over several weeks in young adult mice. In older mice, rearrangements were less common, and synaptic patterns on individual neurons were recognizable for many months to years. Axonal branches frequently retracted or extended on a time scale of minutes in young adult mice, but seldom in mature animals. These results provide direct evidence for a decrease in plasticity of interneuronal connections as animals make the transition from young adulthood to middle age. The long-term stability of synaptic patterns could provide a structural basis for the persistence of memory in the adult nervous system.}, Author = {Gan, Wen-Biao B. and Kwon, Elaine and Feng, Guoping and Sanes, Joshua R. and Lichtman, Jeff W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Aging;Ganglia, Autonomic;research support, u.s. gov't, p.h.s. ;Luminescent Proteins;Microscopy, Confocal;21 Neurophysiology;Synapses;Presynaptic Terminals;research support, non-u.s. gov't ;Time Factors;Mice, Transgenic;Animals;Mice;24 Pubmed search results 2008;Bacterial Proteins}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Department of Anatomy & Neurobiology, Washington University School of Medicine, 660 South Euclid, Box 8108, St. Louis, Missouri 63110, USA.}, Pages = {956-60}, Pii = {nn1115}, Pubmed = {12925856}, Title = {Synaptic dynamism measured over minutes to months: age-dependent decline in an autonomic ganglion}, Uuid = {ED7DC53A-689E-4A2F-90B8-71C1A5EADFD9}, Volume = {6}, Year = {2003}, url = {papers/Gan_NatNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1115}} @article{Ganat:2006, Abstract = {To identify the fates that astroglial cells can attain in the postnatal brain, we generated mice carrying an inducible Cre recombinase (Cre-ER(T2)) controlled by the human GFAP promoter (hGFAP). In mice carrying the GCE (hGFAP-Cre-ER(T2)) transgene, OHT (4-hydroxy-tamoxifen) injections induced Cre recombination in astroglial cells at postnatal day 5 and allowed us to permanently tag these cells with reporter genes. Three days after recombination, reporter-tagged cells were quiescent astroglial cells that expressed the stem cell marker LeX in the subventricular zone (SVZ) and dentate gyrus (DG). After 2-4 weeks, the tagged GFAP lineage included proliferating progenitors expressing the neuronal marker Dcx (Doublecortin) in the SVZ and the DG. After 4 weeks, the GFAP lineage generated mature neurons in the olfactory bulb (OB), DG, and, strikingly, also in the cerebral cortex. A major portion of all neurons in the DG and OB born at the end of the first postnatal week were generated from GFAP+ cells. In addition to neurons, mature oligodendrocytes and astrocytes populating the cerebral cortex and white matter were also the progeny of GFAP+ astroglial ancestors. Thus, genetic fate mapping of postnatal GFAP+ cells reveals that they seed the postnatal brain with neural progenitors/stem cells that in turn give rise to neural precursors and their mature neuronal and oligodendrocytic progeny in many CNS regions, including the cerebral cortex.}, Author = {Ganat, Yosif M. and Silbereis, John and Cave, Clinton and Ngu, Hai and Anderson, George M. and Ohkubo, Yasushi and Ment, Laura R. and Vaccarino, Flora M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Transgenes;Cell Differentiation;research support, n.i.h., extramural ;Astrocytes;Animals;Humans;Brain;Oligodendroglia;Female;Integrases;Mice, Transgenic;Male;research support, non-u.s. gov't ;Cerebral Ventricles;Olfactory Bulb;Cell Lineage;Animals, Newborn;Neurons;Recombination, Genetic;Mice;Promoter Regions (Genetics);24 Pubmed search results 2008;Stem Cells;Glial Fibrillary Acidic Protein}, Month = {8}, Nlm_Id = {8102140}, Number = {33}, Organization = {Child Study Center, Yale University Medical School, New Haven, Connecticut 06520, USA.}, Pages = {8609-21}, Pii = {26/33/8609}, Pubmed = {16914687}, Title = {Early postnatal astroglial cells produce multilineage precursors and neural stem cells in vivo}, Uuid = {A8D22CFF-9EDA-485E-B7AF-3BFC9E93F1EF}, Volume = {26}, Year = {2006}, url = {papers/Ganat_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2532-06.2006}} @article{Ganat:2002, Abstract = {A number of signaling molecules have been implicated in the acute response to hypoxia/ischemia in the adult brain. In contrast, the reaction to chronic hypoxemia is largely unexplored. We used a protocol of chronic hypoxia in rat pups during the first three postnatal weeks, encompassing the period of cellular plasticity in the cerebral cortex. We find that the levels of fibroblast growth factor 1 (FGF1) and FGF2, two members of the FGF family, increase after 2 weeks of chronic hypoxia. In contrast, members of the neurotrophin family are unaffected. FGF2 is normally expressed in the nucleus of mature, glial fibrillary acidic protein (GFAP)-containing astrocytes. Under hypoxia, most FGF2-containing cells do not express detectable levels of GFAP, suggesting that chronic low O(2) induces their transformation into more immature glial phenotypes. Remarkably, hypoxia promotes the appearance of radial glia throughout the sub-ventricular and ependymal zones. Most of these cells express vimentin and brain lipid binding protein. A subset of these radial glial cells expresses FGF receptor 1, and are in close contact with FGF2-positive cells in the sub-ventricular zone. Thus, FGF receptor signaling in radial glia may foster cell genesis after chronic hypoxic damage.From the results of this study we suggest that after the chronic exposure to low levels of oxygen during development, the expression of radial glia increases in the forebrain periventricular region. We envision that astroglia, which are the direct descendants of radial glia, are reverting back to immature glial cells. Alternatively, hypoxia hinders the normal maturation of radial glia into GFAP-expressing astrocytes. Interestingly, hypoxia increases the levels of expression of FGF2, a factor that is essential for neuronal development. Furthermore, chronic hypoxia up-regulated FGF2's major receptor in the periventricular region. Because radial glia have been suggested to play a key role in neurogenesis and cell migration, our data suggests that hypoxia-induced FGF signaling in radial glia may represent part of a conserved program capable of regenerating neurons in the brain after injury. 0306-4522 Journal Article}, Author = {Ganat, Y. and Soni, S. and Chacon, M. and Schwartz, M. L. and Vaccarino, F. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:47 -0400}, Journal = {Neuroscience}, Keywords = {Animals;Neuroglia/*metabolism;Up-Regulation;Rats;D pdf;Cerebral Cortex/metabolism;Receptor Protein-Tyrosine Kinases/*metabolism;Fibroblast Growth Factor 1/*metabolism;Anoxia/*metabolism;Receptors, Fibroblast Growth Factor/*metabolism;Cerebral Ventricles/embryology/*metabolism;Ependyma/embryology/*metabolism;Blotting, Western;06 Adult neurogenesis injury induced;Fibroblast Growth Factor 2/*metabolism;Support, U.S. Gov't, P.H.S.;Enzyme-Linked Immunosorbent Assay;Immunohistochemistry;Regeneration}, Number = {4}, Organization = {Child Study Center, Yale University, 230 South Frontage Road, New Haven, CT 06520, USA.}, Pages = {977-91}, Title = {Chronic hypoxia up-regulates fibroblast growth factor ligands in the perinatal brain and induces fibroblast growth factor-responsive radial glial cells in the sub-ependymal zone}, Uuid = {604CD542-952D-4565-9E2F-59A9575FC663}, Volume = {112}, Year = {2002}, url = {papers/Ganat_Neuroscience2002.pdf}} @article{Garaschuk:1998, Abstract = {1. By applying fura-2-based fluorometric calcium imaging to neonatal rat hippocampal slices we identified a developmentally regulated spontaneous neuronal activity in the CA1 region of the hippocampus. The activity consisted of bursts of intracellular Ca2+ transients recurring synchronously at a slow rate of 0.4-2 min-1 in the entire population of pyramidal neurones and interneurones. 2. These early network oscillations (ENOs) were present during a restricted period of postnatal development. Thus, they were not detected at the day of birth (P0), at P1-P4 they consisted of bursts of large (up to 1.5 microM) Ca2+ transients, gradually transforming into regularly occurring, smaller Ca2+ transients during the subsequent week. Beyond P15-P16 no ENOs were detected. 3. The ENOs were blocked by tetrodotoxin (TTX) and by a reduction in temperature from 33-35 degrees C to 20-22 degrees C. By combining fluorometric imaging with whole-cell current-clamp recordings, we found that each ENO-related Ca2+ transient was associated with a high-frequency (up to 100 Hz) train of action potentials riding on a depolarizing wave. 4. Recordings in the voltage-clamp mode revealed barrages of synaptic currents that were strictly correlated with the ENO-associated Ca2+ transients in neighbouring pyramidal neurones. Perfusing the cells with an intracellular solution that allowed for a discrimination between GABAA and glutamate receptor-mediated currents showed that these barrages of synaptic currents were predominantly of GABAergic origin. 5. The ENOs were totally blocked by the GABAA receptor antagonist bicuculline and they were also substantially reduced by the glutamatergic antagonists D,L-2-amino-5-phosphonovaleric acid (D, L-APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). 6. Synaptic stimulation and application of the GABAA receptor agonist muscimol mimicked the spontaneous Ca2+ transients in pyramidal neurones. The efficacy of muscimol in evoking Ca2+ transients decreased during development in parallel with the gradual disappearance of the ENOs. 7. The developmental decrease in the amplitude of ENO-associated Ca2+ transients occurred in parallel with the transformation of the excitatory synaptic transmission in the hippocampus from the immature GABAergic to the mature glutamatergic form. Thus, at the beginning of the first postnatal week single-shock synaptic stimulation produced Ca2+ transients that were completely blocked by bicuculline. At the end of the second postnatal week the same type of evoked synaptic stimulation produced a Ca2+ transient that was little affected by bicuculline but was abolished by the combined application of D,L-APV and CNQX. 8. These results demonstrate the presence of periodic and spontaneous Ca2+ transients in the majority of pyramidal cells and interneurones of the neonatal CA1 hippocampal network. These ENOs exhibit a highly region-specific developmental profile and may control the activity-dependent wiring of the synaptic connectivity during early postnatal development.}, Author = {Garaschuk, O. and Hanse, E. and Konnerth, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {gamma-Aminobutyric Acid;Electrophysiology;Animals;Synapses;Aging;Rats;in vitro ;Hippocampus;Rats, Wistar;Calcium;21 Calcium imaging;research support, non-u.s. gov't ;Animals, Newborn;Temperature;Nerve Net;21 Neurophysiology;21 Cortical oscillations;24 Pubmed search results 2008;Oscillometry}, Month = {2}, Nlm_Id = {0266262}, Organization = {I. Physiologisches Institut, Universitat des Saarlandes, 66421 Homburg, Germany.}, Pages = {219-36}, Pubmed = {9490842}, Title = {Developmental profile and synaptic origin of early network oscillations in the CA1 region of rat neonatal hippocampus}, Uuid = {3E226CAE-42B6-4391-A741-3199DFBDC033}, Volume = {507 ( Pt 1)}, Year = {1998}, url = {papers/Garaschuk_JPhysiol1998.pdf}} @article{Garaschuk:2000, Abstract = {Two-photon imaging of large neuronal networks in cortical slices of newborn rats revealed synchronized oscillations in intracellular Ca2+ concentration. These spontaneous Ca2+ waves usually started in the posterior cortex and propagated slowly (2.1 mm per second) toward its anterior end. Ca2+ waves were associated with field-potential changes and required activation of AMPA and NMDA receptors. Although GABAA receptors were not involved in wave initiation, the developmental transition of GABAergic transmission from depolarizing to hyperpolarizing (around postnatal day 7) stopped the oscillatory activity. Thus we identified a type of large-scale Ca2+ wave that may regulate long-distance wiring in the immature cortex.}, Author = {Garaschuk, O. and Linn, J. and Eilers, J. and Konnerth, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 03:10:48 +0000}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;gamma-Aminobutyric Acid;Calcium Signaling;Electric Conductivity;In Vitro;Animals;Rats;in vitro ;Hippocampus;Receptors, AMPA;Rats, Wistar;Calcium;Tetrodotoxin;Bicuculline;research support, non-u.s. gov't ;Animals, Newborn;Nerve Net;Cerebral Cortex;21 Neurophysiology;Neurons;Membrane Potentials;Photons;GABA Antagonists;6-Cyano-7-nitroquinoxaline-2,3-dione;Receptors, GABA;Receptors, N-Methyl-D-Aspartate;Research Support, Non-U.S. Gov't;21 Activity-development;Neocortex;calcium imaging;Technique;in vitro;optical physiology;optical imaging;currOpinRvw}, Medline = {20233997}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Institut f{\"u}r Physiologie, Technische Universit{\"a}t M{\"u}nchen, 80802 M{\"u}nchen, Germany.}, Pages = {452-9}, Pubmed = {10769384}, Title = {Large-scale oscillatory calcium waves in the immature cortex}, Uuid = {6A47B021-AADE-4327-A2E0-EBE0B5B5993B}, Volume = {3}, Year = {2000}, url = {papers/Garaschuk_NatNeurosci2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/74823}} @article{Garaschuk:2006, Abstract = {One of the challenges for modern neuroscience is to understand the rules of concerted neuronal function in vivo. This question can be addressed using noninvasive high-resolution imaging techniques like two-photon microscopy. This protocol describes a versatile approach for in vivo two-photon calcium imaging of neural networks, stained with membrane-permeant fluorescent-indicator dyes. It is based on a targeted pressure ejection of the dye into the tissue of interest and can be used for a large spectrum of indicator dyes, including Oregon Green 488 BAPTA-1 acetoxymethyl ester and Fura-2 acetoxymethyl ester. Through the use of dye mixtures and multicolor imaging, this technique allows the visualization of distinct neurons and glial cells up to 500 microm below the brain surface. It is suitable for staining the brain tissue of various different species (e.g., mouse, rat, cat and zebrafish) at all developmental stages. When combined with brain microendoscopy, it allows the monitoring of intracellular calcium signals in awake, behaving animals. The total time required to carry out the protocol, including dissection and cell staining, is approximately 2 h. Thereafter, imaging experiments might be performed for at least 6 h.}, Author = {Garaschuk, Olga and Milos, Ruxandra-Iulia I. and Konnerth, Arthur}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1750-2799}, Journal = {Nat Protoc}, Keywords = {Staining and Labeling;Fluorescent Dyes;Microscopy;Fluorescence;Multiphoton;Nerve Net;Animals;Brain;Mice;calcium imaging;calcium sensor;optical physiology;optical imaging;Technique;}, Nlm_Id = {101284307}, Number = {1}, Organization = {Institut f{\"u}r Physiologie, Ludwig-Maximilians Universit{\"a}t M{\"u}nchen, Pettenkoferstrasse 12, 80336 M{\"u}nchen, Germany.}, Pages = {380-6}, Pii = {nprot.2006.58}, Pubmed = {17406260}, Title = {Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo}, Uuid = {A9A8FD99-5135-4A5F-87A5-537F39755064}, Volume = {1}, Year = {2006}, url = {papers/Garaschuk_NatProtoc2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nprot.2006.58}} @article{Garcia:2004, Abstract = {Establishing the cellular identity in vivo of adult multipotent neural progenitors is fundamental to understanding their biology. We used two transgenic strategies to determine the relative contribution of glial fibrillary acidic protein (GFAP)-expressing progenitors to constitutive neurogenesis in the adult forebrain. Transgenically targeted ablation of dividing GFAP-expressing cells in the adult mouse subependymal and subgranular zones stopped the generation of immunohistochemically identified neuroblasts and new neurons in the olfactory bulb and the hippocampal dentate gyrus. Transgenically targeted cell fate mapping showed that essentially all neuroblasts and neurons newly generated in the adult mouse forebrain in vivo, and in adult multipotent neurospheres in vitro, derived from progenitors that expressed GFAP. Constitutively dividing GFAP-expressing progenitors showed predominantly bipolar or unipolar morphologies with significantly fewer processes than non-neurogenic multipolar astrocytes. These findings identify morphologically distinctive GFAP-expressing progenitor cells as the predominant sources of constitutive adult neurogenesis, and provide new methods for manipulating and investigating these cells.}, Author = {Garcia, A. Denise R. and Doan, Ngan B. and Imura, Tetsuya and Bush, Toby G. and Sofroniew, Michael V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Cell Differentiation;Phosphopyruvate Hydratase;Green Fluorescent Proteins;Immunohistochemistry;Sialic Acids;Thymidine Kinase;Neural Cell Adhesion Molecule L1;Animals;Ganciclovir;Hippocampus;Integrases;Research Support, U.S. Gov't, P.H.S.;Cell Count;Bromodeoxyuridine;Analysis of Variance;Olfactory Bulb;Microtubule-Associated Proteins;Tubulin;Gene Expression Regulation;Neuropeptides;Comparative Study;Glial Fibrillary Acidic Protein;beta-Galactosidase;Neuroglia;Prosencephalon;Cell Size;Stem Cells;Mice;Research Support, Non-U.S. Gov't;Neurons;Mice, Transgenic}, Month = {11}, Nlm_Id = {9809671}, Number = {11}, Organization = {Department of Neurobiology and Brain Research Institute, University of California, Los Angeles, California 90095-1763, USA.}, Pages = {1233-41}, Pii = {nn1340}, Pubmed = {15494728}, Title = {GFAP-expressing progenitors are the principal source of constitutive neurogenesis in adult mouse forebrain}, Uuid = {D6F585BF-C9B5-11DA-8A64-000D9346EC2A}, Volume = {7}, Year = {2004}, url = {papers/Garcia_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1340}} @article{Garcia-Valenzuela:1999, Abstract = {Following optic nerve transection, most of the retinal ganglion cells die. Their debris is promptly cleared by phagocytic cells. It is currently not known to what extent peripherally derived macrophages contribute to this activity. Using antibodies OX42 and ED-1, phagocytic cells were labeled in the retinas of optic nerve lesioned adult rats. To distinguish whether the cells were reactive microglial or macrophagic in origin, blood-borne monocytes were labeled with fluorescent microspheres while in the systemic circulation. Macrophages invaded the retina, but only in the nerve fiber layer, sparing the ganglion cell and other layers. These macrophages engulfed only the axonal debris from dying ganglion cells, not their degenerating cell bodies. These results indicate that although peripherally derived monocytic cells are recruited into the retrogradely degenerating retina, their role in clearing debris is limited to the optic fiber layer.}, Author = {Garcia-Valenzuela, E. and Sharma, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Retina;Glial Fibrillary Acidic Protein;Phagocytosis;Animals;Macrophages;Rats;Microscopy, Confocal;Microglia;Optic Nerve;Antigens, Surface;Rats, Wistar;Not relevant;11 Glia;Time Factors;Membrane Glycoproteins;Axotomy;Support, U.S. Gov't, P.H.S.;Retinal Ganglion Cells}, Medline = {99326793}, Month = {7}, Nlm_Id = {0213640}, Number = {1}, Organization = {Departments of Cell Biology and Anatomy and Ophthalmology, New York Medical College, Valhalla, New York 10595, USA.}, Pages = {55-66}, Pii = {10.1002/(SICI)1097-4695(199907)40:1<55::AID-NEU5>3.0.CO;2-E}, Pubmed = {10398071}, Title = {Laminar restriction of retinal macrophagic response to optic nerve axotomy in the rat}, Uuid = {D82C3775-E8DF-41CD-9E0C-5444CA4ACFE1}, Volume = {40}, Year = {1999}, url = {papers/Garcia-Valenzuela_JNeurobiol1999.pdf}} @article{Garcia-Verdugo:1998, Abstract = {Neural stem cells are maintained in the subventricular zone (SVZ) of the adult mammalian brain. Here, we review the cellular organization of this germinal layer and propose lineage relationships of the three main cell types found in this area. The majority of cells in the adult SVZ are migrating neuroblasts (type A cells) that continue to proliferate. These cells form an extensive network of tangentially oriented pathways throughout the lateral wall of the lateral ventricle. Type A cells move long distances through this network at high speeds by means of chain migration. Cells in the SVZ network enter the rostral migratory stream (RMS) and migrate anteriorly into the olfactory bulb, where they differentiate into interneurons. The chains of type A cells are ensheathed by slowly proliferating astrocytes (type B cells), the second most common cell type in this germinal layer. The most actively proliferating cells in the SVZ, type C, form small clusters dispersed throughout the network. These foci of proliferating type C cells are in close proximity to chains of type A cells. We discuss possible lineage relationships among these cells and hypothesize which are the neural stem cells in the adult SVZ. In addition, we suggest that interactions between type A, B, and C cells may regulate proliferation and initial differentiation within this germinal layer.}, Author = {Garcia-Verdugo, J. M. and Doetsch, F. and Wichterle, H. and Lim, D. A. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurobiol}, Keywords = {02 Adult neurogenesis migration;Cell Division/physiology;Cerebral Ventricles/*cytology/embryology/growth &development;Interneurons/cytology;Olfactory Bulb/cytology;Neurons/*cytology/physiology;Stem Cells/*cytology/physiology;03 Adult neurogenesis progenitor source;Animal;Support, U.S. Gov't, P.H.S.;BB;Cell Movement/physiology}, Number = {2}, Organization = {University of Valencia, Spain.}, Pages = {234-48.}, Title = {Architecture and cell types of the adult subventricular zone: in search of the stem cells}, Uuid = {771B0138-B931-4335-838A-83A8C4E2D946}, Volume = {36}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9712307}} @article{Garel:2004, Abstract = {Topography of axonal projections has been generally thought to arise from positional information located within the projecting and targeted structures, independent of events along the path or within the axonal bundle. Recent evidence suggests that in the projection from the dorsal thalamus to the neocortex, initial rostrocaudal targeting of axons is regulated at the level of an intermediate target, the subcortical telencephalon. In this system, thalamic axons are spatially positioned within the subcortical telencephalon, partly via interactions between EphAs and ephrin-As, and this positioning apparently determines the rostrocaudal level of the neocortex that the axons will initially target.}, Author = {Garel, Sonia and Rubenstein, John L. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {10 Development;Transcription Factors;Animals;Humans;Carrier Proteins;Mice, Mutant Strains;Neural Pathways;Basic Helix-Loop-Helix Transcription Factors;Receptors, Eph Family;Homeodomain Proteins;Axons;review;10 circuit formation;Thalamus;Cerebral Cortex;Mice;24 Pubmed search results 2008;Growth Cones;Nerve Tissue Proteins;Models, Neurological;Brain Mapping}, Month = {9}, Nlm_Id = {7808616}, Number = {9}, Organization = {INSERM U368, Ecole Normale Sup{\'e}rieure- 46 rue d'Ulm 75230 Paris cedex 05, France.}, Pages = {533-9}, Pii = {S0166-2236(04)00206-1}, Pubmed = {15331235}, Title = {Intermediate targets in formation of topographic projections: inputs from the thalamocortical system}, Uuid = {13F7AE16-DAB7-443D-9042-2B0BBBB472B9}, Volume = {27}, Year = {2004}, url = {papers/Garel_TrendsNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2004.06.014}} @article{Garland:2007, Abstract = {CASE:: Tony is an 11-year old boy in the fifth grade whose mother describes him as "really a good kid who is bright and tries to be friendly. But he's always doing things that get him in trouble at school and sometimes at home." Tony was diagnosed with ADHD (combined type) 2 years ago. Stimulant therapy improved his attention and concentration during school, decreased hyperactivity in the classroom and improved educational achievements. However, Tony is oppositional and disruptive on the playground, during team sports and at home. His teacher observed that he wants to fit in, but he quickly gets in arguments with other children. He has difficulty sustaining friendships because he typically annoys others with unreasonable demands. He often has temper tantrums when things do not go his way; the tantrums are not prolonged but frequent. At home, on several occasions Tony hit his younger sister, and he once threw a dinner plate against the wall during a family meal. Although his mother describes these behaviors as present for many years, they seem to be escalating. Tony lives with both parents and his younger sister. There is no history of marital discord or major life event change in the past year. Standardized achievement tests demonstrate average to above average achievement scores. He continues to get mostly B grades and an occasional C. Tony's parents have tried to limit television time as a punishment for disruptive behaviors without any apparent effect. His mother reports that she yelled at him on several occasions when he refused to carry out household chores. "He gets angry at the simplest request for help." After meeting with Tony and his mother and completing a normal physical examination, the pediatrician referred Tony to a child psychologist for behavioral therapy.}, Author = {Garland, Ann and Augustyn, Marilyn and Stein, Martin T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0196-206X}, Journal = {J Dev Behav Pediatr}, Keywords = {24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8006933}, Number = {5}, Pages = {406-8}, Pii = {00004703-200710000-00012}, Pubmed = {18049326}, Title = {Disruptive and oppositional behavior in an 11-year old boy}, Uuid = {E8B87309-9595-4384-9C99-398E6E736F45}, Volume = {28}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1097/DBP.0b013e3181570cf1}} @article{Garnier:1996, Abstract = {Several recent experiments using neocortical transplantation paradigms indicated that embryonic neurons grafted in a heterotopic locus retain development characteristics corresponding to their site of origin. In the present study, limited portions of lateral (lateral-to-lateral) or medial (medial-to-lateral) sectors of embryonic (E16) frontal cortex were grafted into the lateral frontal cortex of newborn rats. A retrograde tracer was injected 3-4 months later into the dorsomedial or ventrolateral sectors of the host caudate-putamen (CPU). The results indicate that the mediolateral arrangement of striatal projection developed by lateral-to-lateral transplants is virtually identical to that found in intact rats. A very weak proportion of the transplanted cells distribute fibers to the dorsomedial sector of the CPU. In marked contrast, the proportion of efferents from medial-to-lateral transplants projecting to the dorsomedial CPU is by far larger than the one directed to the ventrolateral CPU. Our findings provide evidence that even within one single neocortical area (the frontal neocortex) some degree of prespecification (medial versus lateral patterns of efferent projections) is already present at E16.}, Author = {Garnier, C. and Arnault, P. and L{\'e}tang, J. and Roger, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Neostriatum;Frontal Lobe;Cell Differentiation;Brain Tissue Transplantation;Rats;Neural Pathways;Rats, Wistar;Silver Staining;Cholera Toxin;Animals, Newborn;Age Factors;Animals;24 Pubmed search results 2008;Fetal Tissue Transplantation;Microinjections}, Medline = {97001714}, Month = {7}, Nlm_Id = {7600130}, Number = {1}, Organization = {CNRS, URA 1869, D{\'e}partement des Neurosciences, Facult{\'e} des Sciences, Universit{\'e} de Poitiers, France.}, Pages = {33-6}, Pii = {0304394096128330}, Pubmed = {8844706}, Title = {Development of projections from transplants of embryonic medial or lateral frontal cortex placed in the lateral frontal cortex of newborn hosts}, Uuid = {5D090C26-63E1-4037-9587-5571FC419E46}, Volume = {213}, Year = {1996}} @article{Garnier:1997, Abstract = {The present study was designed to further investigate the effects of intrinsic or extrinsic influences on the development of the efferent connectivity of frontal neocortical neurons. The lateral or medial parts of the frontal neocortex of embryonic (E) day 16 fetuses were grafted into homo- (medial-to-medial) or heterotopic (lateral-to-medial) position in the medial part of the left frontal cortex of newborn hosts. Three to four months after grafting, a retrograde neurotracer was injected into the dorsomedial or ventrolateral quadrant of the left caudate-putamen (CPU). The ensuing retrograde labeling in the transplants was then compared to that found in an equivalent cortical area in control animals. Medial-to-medial transplants developed a striatal projection whose mediolateral organization conforms to that of the projection arising from the medial part of the intact frontal cortex. The mediolateral distribution of the projection arising from lateral-to-medial transplants was not fundamentally different from that originating from medial-to-medial transplants, a finding which stands in marked contrast with what was found recently [7] with medial-to-lateral transplants. These results indicate that inside the frontal cortex, different subregions are not totally interchangeable, at least in terms of development of efferent connectivity.}, Author = {Garnier, C. and Arnault, P. and Roger, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Neostriatum;Brain Tissue Transplantation;Rats;Female;Neural Pathways;Silver Staining;Rats, Wistar;Neocortex;Animals, Newborn;Animals;Male;24 Pubmed search results 2008;Fetal Tissue Transplantation;Neurons}, Medline = {98049459}, Month = {10}, Nlm_Id = {7600130}, Number = {1-2}, Organization = {CNRS, UMR 6558, D{\'e}partement des Neurosciences, Facult{\'e} des Sciences, Poitiers, France.}, Pages = {41-4}, Pubmed = {9389591}, Title = {Development of the striatal projection from embryonic neurons from the lateral or medial frontal cortex grafted homo- or heterotopically into the medial frontal cortex of newborn rats}, Uuid = {46EF58E9-63F2-4CC0-B283-3D6E1DEAEC29}, Volume = {235}, Year = {1997}} @article{Gartside:1979, Author = {Gartside, I. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Epilepsy;Electroencephalography;21 Neurophysiology;Rats;Cortical Synchronization;Animals;24 Pubmed search results 2008;21 Epilepsy}, Medline = {79218545}, Month = {4}, Nlm_Id = {0266262}, Pages = {6P}, Pubmed = {458698}, Title = {A demonstration of the influence of electrocortical synchrony on the occurrence of epileptiform spiking in the anaesthetized rat [proceedings]}, Uuid = {C2755C0E-951A-475C-ADF3-3D2C66CEBCBE}, Volume = {289}, Year = {1979}} @article{Gascon:2006, Abstract = {The initial formation and growth of dendrites is a critical step leading to the integration of newly generated neurons into postnatal functional networks. However, the cellular mechanisms and extracellular signals regulating this process remain mostly unknown. By directly observing newborn neurons derived from the subventricular zone in culture as well as in olfactory bulb slices, we show that ambient GABA acting through GABA(A) receptors is essential for the temporal stability of lamellipodial protrusions in dendritic growth cones but did not interfere with filopodia dynamics. Furthermore, we provide direct evidence that ambient GABA is required for the proper initiation and elongation of dendrites by promoting the rapid stabilization of new dendritic segments after their extension. The effects of GABA on the initial formation of dendrites depend on depolarization and Ca2+ influx and are associated with a higher stability of microtubules. Together, our results indicate that ambient GABA is a key regulator of dendritic initiation in postnatally generated olfactory interneurons and offer a mechanism by which this neurotransmitter drives early dendritic growth.}, Author = {Gascon, Eduardo and Dayer, Alexandre G. and Sauvain, Marc-Olivier O. and Potter, Gael and Jenny, Benoit and De Roo, Mathias and Zgraggen, Eloisa and Demaurex, Nicolas and Muller, Dominique and Kiss, Jozsef Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008;research support, non-u.s. gov't;Dendrites;Rats, Sprague-Dawley;Rats;Pseudopodia;Growth Cones;comparative study;Animals, Newborn;Interneurons;Animals;Cells, Cultured;Olfactory Bulb;gamma-Aminobutyric Acid;Receptors, GABA-A}, Month = {12}, Nlm_Id = {8102140}, Number = {50}, Organization = {Department of Neuroscience, University of Geneva Medical School, CH-1211 Geneva, Switzerland.}, Pages = {12956-66}, Pii = {26/50/12956}, Pubmed = {17167085}, Title = {GABA regulates dendritic growth by stabilizing lamellipodia in newly generated interneurons of the olfactory bulb}, Uuid = {FA791193-EE8C-4B44-8A84-33DCD5322841}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4508-06.2006}} @article{Gates:1995, Abstract = {The subventricular zone (SVZ) of the lateral ventricle remains mitotically active in the adult mammalian central nervous system (CNS). Recent studies have suggested that this region may contain neuronal precursors (neural stem cells) in adult rodents. A variety of neuronal and glial markers as well as three extracellular matrix (ECM) markers were examined with the hope of understanding factors that may affect the growth and migration of neurons from this region throughout development and in the adult. This study has characterized the subventricular zone of late embryonic, postnatal, and adult mice using several neuronal markers [TuJ1, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), neuron-specific enolase (NSE)], glial markers [RC-2, vimentin, glial fibrillary acidic protein (GFAP), galactocerebroside (Gal-C)], ECM markers [tenascin-C (TN-C), chondroitin sulfate, a chondroitin sulfate proteoglycan termed dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG)], stem-cell marker (nestin), and proliferation-specific marker [bromodeoxyuridine (BrdU)]. TuJ1+ and nestin+ cells (neurons and stem cells, respectively) persist in the region into adulthood, although the numbers of these cells become more sparse as the animal develops, and they appear to be immature compared to the cells in surrounding forebrain structures (e.g., not expressing NSE and having few, if any, processes). Likewise, NADPH-d+ cells are found in and around the SVZ during early postnatal development but become more sparse in the proliferative zone through maturity, and, by adulthood, only a few labeled cells can be found at the border between the SVZ and surrounding forebrain structures (e.g., the striatum), and even smaller numbers of positive cells can be found within the adult SVZ proper. BrdU labeling also seems to decrease significantly after the first postnatal week, but it still persists in the SVZ of adult animals. The disappearance of RC-2+ (radial) glia during postnatal development and the persistence of glial-derived ECM molecules such as tenascin and chondroitin sulfate proteoglycans (as well as other "boundary"molecules) in the adult SVZ may be associated with a persistence of immaturity, cell death, and a lack of cell emigration from the SVZ in the adult. 0021-9967 Journal Article}, Author = {Gates, M. A. and Thomas, L. B. and Howard, E. M. and Laywell, E. D. and Sajin, B. and Faissner, A. and Gotz, B. and Silver, J. and Steindler, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Comp Neurol}, Keywords = {In Situ Hybridization;Embryo/cytology/*metabolism;Neurons/cytology/metabolism;02 Adult neurogenesis migration;Aging/metabolism;Immunohistochemistry;B, G abstr;Extracellular Matrix/metabolism;Biological Markers;Brain/cytology/*embryology/*growth &development;Cell Division;Animals, Newborn;Support, U.S. Gov't, P.H.S.;Animals;Cerebral Ventricles;Support, Non-U.S. Gov't;Mice}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, University of Tennessee, Memphis 38163, USA.}, Pages = {249-66}, Pubmed = {8543661}, Title = {Cell and molecular analysis of the developing and adult mouse subventricular zone of the cerebral hemispheres}, Uuid = {BE1CEA9B-6144-4C81-B543-E6013567D349}, Volume = {361}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8543661}} @book{Gazzaniga:1995, Abstract = {93040288 Michael S. Gazzaniga, editor-in-chief ; section editors, Emilio Bizzi ... [et al.]. ill. (some col.) ; 28 cm. "A Bradford book."}, Author = {Gazzaniga, Michael S. and Bizzi, Emilio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Isbn = {0262071576}, Keywords = {Cognition physiology.;Cognitive neuroscience.;M QP360.5 .C643 1995 153;Brain physiology.}, Publisher = {MIT Press}, Title = {The cognitive neurosciences}, Uuid = {C8A9D979-32A5-4041-B209-89E762EB044A}, Year = {1995}} @article{Ge:2006, Abstract = {Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (gamma-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.}, Author = {Ge, Shaoyu and Goh, Eyleen L. K. and Sailor, Kurt A. and Kitabatake, Yasuji and Ming, Guo-li L. and Song, Hongjun}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {01 Adult neurogenesis general;04 Adult neurogenesis factors}, Month = {2}, Nlm_Id = {0410462}, Number = {7076}, Organization = {Institute for Cell Engineering, Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, Pages = {589-93}, Pii = {nature04404}, Pubmed = {16341203}, Title = {GABA regulates synaptic integration of newly generated neurons in the adult brain}, Uuid = {85E9564C-A32E-4FA1-AADE-1D7463C8EF8D}, Volume = {439}, Year = {2006}, url = {papers/Ge_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04404}} @article{Ge:2007, Abstract = {GABA, a major inhibitory neurotransmitter in the adult brain, activates synaptic and extrasynaptic GABA(A) receptors, causing hyperpolarization of mature neurons. As in the embryonic nervous system, GABA depolarizes neural progenitors and immature neurons in the adult brain. Several recent studies have suggested that GABA has crucial roles in regulating different steps of adult neurogenesis, including proliferation of neural progenitors, migration and differentiation of neuroblasts, and synaptic integration of newborn neurons. Here, we review recent findings on how GABA regulates adult neurogenesis in the subventricular zone of the lateral ventricles and in the dentate gyrus of the hippocampus. We also discuss an emerging view that GABA serves as a key mediator of neuronal activity in setting the tempo of adult neurogenesis.}, Author = {Ge, Shaoyu and Pradhan, Dennis A. and Ming, Guo-Li L. and Song, Hongjun}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {7808616}, Number = {1}, Organization = {Institute for Cell Engineering, Departments of Neurology and Neuroscience, Johns Hopkins University School of Medicine, 733 North Broadway, BRB 735, Baltimore, MD 21205, USA.}, Pages = {1-8}, Pii = {S0166-2236(06)00263-3}, Pubmed = {17116335}, Title = {GABA sets the tempo for activity-dependent adult neurogenesis}, Uuid = {AC58AB97-DBC3-4F1F-B1F5-4AD17370DED0}, Volume = {30}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.11.001}} @article{Gehrmann:1995, Abstract = {Microglia form a regularly spaced network of resident glial cells throughout the central nervous system (CNS). They are morphologically, immunophenotypically and functionally related to cells of the monocyte/macrophage lineage. In the ultimate vicinity of the blood-brain barrier two specialized subsets of macrophages/microglia can be distinguished: firstly, perivascular cells which are enclosed within the basal lamina and secondly juxtavascular microglia which make direct contact with the parenchymal side of the CNS vascular basal lamina but represent true intraparenchymal resident microglia. Bone marrow chimera experiments indicates that a high percentage of the perivascular cells undergoes replacement with bone marrow-derived cells. In contrast, juxtavascular microglia like other resident microglia form a highly stable pool of CNS cells with extremely little turnover with the bone marrow compartment. Both the perivascular cells and the juxtavascular microglia play an important role in initiating and maintaining CNS autoimmune injury due to their strategic localization at a site close to the blood-brain barrier, their rapid inducibility for MHC class II antigens and their potential scavenger role as phagocytic cells. The constantly replaced pool of perivascular cells probably represents an entry route by which HIV gets access to the brain. Microglia are the first cell type to respond to several types of CNS injury. Microglial activation involves a stereotypic pattern of cellular responses, such as proliferation, increased or de-novo expression of immunomolecules, recruitment to the site of injury and functional changes, e.g., the release of cytotoxic and/or inflammatory mediators. In addition, microglia have a strong antigen presenting function and a pronounced cytotoxic function. Microglial activation is a graded response, i.e., microglia only transform into intrinsic brain phagocytes under conditions of neuronal and or synaptic/terminal degeneration. In T-cell-mediated autoimmune injury of the nervous system, microglial activation follows these lines and occurs at an early stage of disease development. In experimental autoimmune encephalomyelitis (EAE), microglia proliferate vigorously, show a strong expression of MHC class I and II antigens, cell adhesion molecules, release of reactive oxygen intermediates and inflammatory cytokines and transform into phagocytic cells. Due to their pronounced antigen presenting function in vitro, activated microglia rather than astrocytes or endothelial cells are the candidates as intrinsic antigen presenting cel of the brain. In contrast to microglia, astrocytes react with a delay, appear to encase morphologically the inflammatory lesion and may be instrumental in downregulating the T-cell-mediated immune injury by inducing T-cell apoptosis.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Gehrmann, J. and Matsumoto, Y. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0165-0173}, Journal = {Brain Res Brain Res Rev}, Keywords = {Research Support, Non-U.S. Gov't;11 Glia;Microglia;review, tutorial;Brain;review}, Medline = {96031752}, Month = {3}, Nlm_Id = {8908638}, Number = {3}, Organization = {Department of Pathology, University Hospital, Z{\"u}rich, Switzerland.}, Pages = {269-87}, Pii = {016501739400015H}, Pubmed = {7550361}, Title = {Microglia: intrinsic immuneffector cell of the brain}, Uuid = {420EE321-E693-4444-8CB0-6F73D2EC7E2E}, Volume = {20}, Year = {1995}} @article{Georges:2001, Abstract = {Genetically modified donor T cells with an inducible "suicide" gene have the potential to improve the safety and availability of allogeneic hematopoietic stem cell transplantation by enhancing engraftment and permitting control of graft-versus-host disease (GVHD). However, several clinical studies of gene-modified T cells have shown limited to no in vivo function of the ex vivo expanded T cells. Using the well-established dog model of allogeneic marrow transplantation, the question was asked if retrovirally transduced, donor derived, ex vivo expanded cytotoxic T lymphocytes (CTLs) that are recipient specific could enhance engraftment of dog leukocyte antigen (DLA)-haploidentical marrow following a single dose of 9.2 Gy total body irradiation and no postgrafting immunosuppression. In this setting, only 4 of 11 control recipients of DLA-haploidentical marrow without added CTLs engrafted. CTLs did not enhance engraftment of CD34(+) selected peripheral blood stem cells. However, recipient-specific CTLs enhanced engraftment of DLA-haploidentical marrow in 9 of 11 evaluable recipients (P =.049). All dogs that engrafted developed multiorgan GVHD. To facilitate in vivo tracking, 8 dogs received CTLs transduced with a retroviral vector encoding green fluorescent protein (GFP) and neomycin phosphotransferase (neo). Recipients that engrafted had sharp increases in the numbers of circulating GFP(+) CTLs on days +5 to +6 after transplantation. GFP(+) CTLs isolated from blood were capable of recipient-specific lysis. At necropsy, up to 7.1\%of CD3(+) cells in tissues were GFP(+) and polymerase chain reaction in situ hybridization for neo showed infiltration of transduced CTLs in GVHD-affected organs. These results show that ex vivo expanded, transduced T cells maintained in vivo function and enhanced marrow engraftment.}, Author = {Georges, G. E. and Storb, R. and Bruno, B. and Brodie, S. J. and Thompson, J. D. and Taranova, A. G. and Zaucha, J. M. and Little, M. T. and Zellmer, E. and Moore, P. F. and Gooley, T. and Sale, G. and Kiem, H. P. and Sandmaier, B. M. and Lyons, R. M. and Nash, R. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Histocompatibility;Research Support, Non-U.S. Gov't;Animals;Cell Separation;Whole-Body Irradiation;Transfection;Bone Marrow Transplantation;Kanamycin Kinase;Retroviridae;Antigens, CD34;11 Glia;Green Fluorescent Proteins;Genetic Vectors;In Situ Hybridization;Haplotypes;Research Support, U.S. Gov't, P.H.S.;T-Lymphocytes, Cytotoxic;Transplantation, Homologous;Graft Rejection;Polymerase Chain Reaction;Graft vs Host Disease;Luminescent Proteins;Graft Survival;Gene Expression;Dogs;HLA Antigens}, Medline = {21575734}, Month = {12}, Nlm_Id = {7603509}, Number = {12}, Organization = {Clinical Research Division, Fred Hutchinson Cancer Research Center, University of Washington, Seattle 98109, USA. ggeorges\@fhcrc.org}, Pages = {3447-55}, Pubmed = {11719387}, Title = {Engraftment of DLA-haploidentical marrow with ex vivo expanded, retrovirally transduced cytotoxic T lymphocytes}, Uuid = {895C165A-D9F9-47E7-BB3B-AF130D193B77}, Volume = {98}, Year = {2001}} @article{Gerfen:1989, Abstract = {The basal ganglia, of which the striatum is the major component, process inputs from virtually all cerebral cortical areas to affect motor, emotional, and cognitive behaviors. Insights into how these seemingly disparate functions may be integrated have emerged from studies that have demonstrated that the mammalian striatum is composed of two compartments arranged as a mosaic, the patches and the matrix, which differ in their neurochemical and neuroanatomical properties. In this study, projections from prefrontal, cingulate, and motor cortical areas to the striatal compartments were examined with the Phaseolus vulgaris-leucoagglutinin (PHA-L) anterograde axonal tracer in rats. Each cortical area projects to both the patches and the matrix of the striatum; however, deep layer V and layer VI corticostriatal neurons project principally to the patches, whereas superficial layer V and layer III and II corticostriatal neurons project principally to the matrix. The relative contribution of patch and matrix corticostriatal projections varies among the cortical areas examined such that allocortical areas provide a greater number of inputs to the patches than to the matrix, whereas the reverse obtains for neocortical areas. These results demonstrate that the compartmental organization of corticostriatal inputs is related to their laminar origin and secondarily to the cytoarchitectonic area of origin.}, Author = {Gerfen, C. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {21 Neurophysiology;Rats;Immunohistochemistry;Corpus Striatum;Phytohemagglutinins;21 Circuit structure-function;Animals;Rats, Inbred Strains;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0404511}, Number = {4928}, Organization = {Laboratory of Cell Biology, National Institute of Mental Health, Bethesda, MD 20892.}, Pages = {385-8}, Pubmed = {2799392}, Title = {The neostriatal mosaic: striatal patch-matrix organization is related to cortical lamination}, Uuid = {F2173F83-7790-46BF-B5B6-2626799EC2F4}, Volume = {246}, Year = {1989}} @article{German:2002, Abstract = {A mouse model of Niemann-Pick type C disease has been found that exhibits neuropathology similar to the human condition. There is an age-related neurodegeneration in several brain regions and a lack of myelin in the corpus callosum in these mice. The purpose of the present study was to examine the Niemann-Pick mouse and determine whether: (1) microglia and astrocytes exhibit ultrastructural pathology similar to that found in neurons; (2) nerve fiber number is reduced when the myelin sheath is absent; and (3) the lysosomal hydrolase, cathepsin-D, is involved in the neurodegenerative process. Using light and electron microscopic methods, and immunocytochemistry, Niemann-Pick and control animals were examined at several ages. Cathepsin-D content was semi-quantitatively measured in neurons and glial cells in brain regions known to exhibit neurodegeneration, as was the density of glial fibrillary acidic protein-labeled astrocytes. The Niemann-Pick mouse exhibited: (1) an age-related increase in inclusion bodies in microglia and astrocytes, similar to that observed within neurons; (2) an almost complete absence of myelin in the corpus callosum by 7-8 weeks of age, along with a 30\%reduction in the number of corpus callosum axons; (3) a mild age-related increase in cathepsin-D content within nerve cells in many brain regions. However, the cathepsin-D elevation was greatest in microglial cells; (4) an age-related increase in the number of microglial cells containing intense cathepsin-D immunoreactivity in both the thalamus and cerebellum. Both of these brain regions have been shown previously to exhibit an age-related loss of neurons; and (5) an increase in the number of reactive astrocytes immunostained for glial fibrillary acidic protein, especially in the thalamus and cerebellum.These data indicate that glial cells are a major target for pathology in the Niemann-Pick mouse. The lack of myelin within the corpus callosum may be related to the loss of nerve fibers in this structure. The increase in cathepsin-D-laden microglial cells, in brain regions previously shown to undergo neurodegeneration, is consistent with a role for microglia in the phagocytosis of dead neurons and in actively contributing to the neurodegenerative process. The activation of astrocytes in regions that undergo neurodegeneration is also consistent with a role for these glial cells in the neurodegenerative process.}, Author = {German, D. C. and Liang, C-L L. and Song, T. and Yazdani, U. and Xie, C. and Dietschy, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Animals;Proteins;Brain;Microglia;Female;Cell Count;Cathepsin D;Nerve Fibers, Myelinated;Not relevant;Disease Models, Animal;Male;11 Glia;Mice, Neurologic Mutants;Support, Non-U.S. Gov't;Wallerian Degeneration;Cell Size;Neuroglia;Support, U.S. Gov't, P.H.S.;Inclusion Bodies;Mice;Niemann-Pick Diseases;Microscopy, Electron;Corpus Callosum;Immunohistochemistry}, Medline = {21681898}, Nlm_Id = {7605074}, Number = {3}, Organization = {Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9070, USA. dwight.german\@utsouthwestern.edu}, Pages = {437-50}, Pii = {S0306452201005176}, Pubmed = {11823057}, Title = {Neurodegeneration in the Niemann-Pick C mouse: glial involvement}, Uuid = {8713B419-812C-40DF-B669-3EB2AAA65D9D}, Volume = {109}, Year = {2002}} @article{Germano:1998, Abstract = {Recent clinical and laboratory data suggest that there is a link between neuronal migration disorders (NMD) and increased seizure threshold. To characterize an animal model with features similar to human NMD and to assess seizure susceptibility, NMD were induced in the rat at the time of neuroblastic division (PG15) and three other gestational ages (PG 13, PG14, PG16) by transplacental exposure to methylaxozymethanol (MAM, 25 mg/kg). Offspring pups were monitored for spontaneous and electrographic seizures. At postnatal day 14, randomly selected rat pups were sacrificed for histological examination. In other MAM-exposed pups and controls, status epilepticus was induced by intraperitoneal administration of kainic acid. On histology, NMD were found in all PG 15 MAM-exposed rats, in comparison to 63\%of PG 13, 70\%of PG 14, 80\%of PG16. Histological features included cortical laminar disorganization, ectopic neurons in the subcortical white matter and in cortical layer I, persistent granular layer, marginal glioneuronal heterotopia, and discrete areas of neuronal ectopia in the CA1 subfield of the hippocampus. Based on the severity of the neuronal migration abnormalities, rats were divided into three categories: severe, moderate, and mild. Severe and moderate NMD were only found in the PG 15 MAM-exposed rats. EEG recording in rats with NMD did not disclose spontaneous seizures; however, rats with severe NMD had higher slow wave activity compared to controls (P < .05). MAM-exposed rats with severe NMD were more susceptible to kainic-induced seizures compared to controls (P < .05). In rats with severe NMD, kainic acid-induced status epilepticus produced hippocampal damage in the CA3/4 region. These results demonstrate that MAM-induced NMD have histological and electrographic characteristics similar to human NMD. The severity of neuronal abnormality depends on the time of transplacental exposure as the most severe NMD were found after exposure to MAM at the time of neuroblastic division. The degree of NMD positively correlates with seizure susceptibility, since only rats with severe NMD have decreased seizure threshold. The occurrence of status epilepticus-induced hippocampal damage in pups with severe NMD suggests that the severely compromised hippocampus is less resistant to seizure-induced injury than the normal developing brain.}, Author = {Germano, I. M. and Sperber, E. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Research Support, Non-U.S. Gov't;Pregnancy;Animals;Rats;Seizures;Brain;21 Epilepsy;Female;Epilepsy;Rats, Sprague-Dawley;Hippocampus;Cell Movement;Maternal-Fetal Exchange;Disease Models, Animal;Behavior, Animal;Research Support, U.S. Gov't, P.H.S.;Body Weight;21 Neurophysiology;Methylazoxymethanol Acetate;Neurons;Organ Size;Litter Size;24 Pubmed search results 2008;Gestational Age;Electroencephalography;Brain Mapping}, Medline = {98173135}, Month = {2}, Nlm_Id = {7600111}, Number = {4}, Organization = {Department of Neurosurgery, Mount Sinai School of Medicine, New York, New York 10029, USA.}, Pages = {473-88}, Pii = {10.1002/(SICI)1097-4547(19980215)51:4<473::AID-JNR7>3.0.CO;2-9}, Pubmed = {9514201}, Title = {Transplacentally induced neuronal migration disorders: an animal model for the study of the epilepsies}, Uuid = {292D3A98-CA17-40CD-8FBB-2E972D4C4B3C}, Volume = {51}, Year = {1998}} @article{Ghanem:2007, Abstract = {Distinct subtypes of cortical GABAergic interneurons provide inhibitory signals that are indispensable for neural network function. The Dlx homeobox genes have a central role in regulating their development and function. We have characterized the activity of three cis-regulatory sequences involved in forebrain expression of vertebrate Dlx genes: upstream regulatory element 2 (URE2), I12b, and I56i. The three regulatory elements display regional and temporal differences in their activities within the lateral ganglionic eminence (LGE), medial ganglionic eminence (MGE), and caudal ganglionic eminence (CGE) and label distinct populations of tangentially migrating neurons at embryonic day 12.5 (E12.5) and E13.5. We provide evidence that the dorsomedial and ventral MGE are distinct sources of tangentially migrating neurons during midgestation. In the adult cortex, URE2 and I12b/I56i are differentially expressed in parvalbumin-, calretinin-, neuropeptide Y-, and neuronal nitric oxide synthase-positive interneurons; I12b and I56i were specifically active in somatostatin-, vasoactive intestinal peptide-, and calbindin-positive interneurons. These data suggest that interneuron subtypes use distinct combinations of Dlx1/Dlx2 enhancers from the time they are specified through adulthood.}, Author = {Ghanem, No{\"e}l and Yu, Man and Long, Jason and Hatch, Gary and Rubenstein, John L. R. and Ekker, Marc}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;10 Development;research support, n.i.h., extramural;12 Interneuron development;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8102140}, Number = {19}, Organization = {Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5.}, Pages = {5012-22}, Pii = {27/19/5012}, Pubmed = {17494687}, Title = {Distinct cis-regulatory elements from the Dlx1/Dlx2 locus mark different progenitor cell populations in the ganglionic eminences and different subtypes of adult cortical interneurons}, Uuid = {48D9C141-C7B8-4922-BAB8-5AC6EA05EF34}, Volume = {27}, Year = {2007}, url = {papers/Ghanem_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4725-06.2007}} @article{Ghashghaei:2006, Abstract = {Coordinated regulation of neuronal progenitor differentiation in the subventricular zone (SVZ) is a fundamental feature of adult neurogenesis. However, the molecular control of this process remains mostly undeciphered. Here, we investigate the role of neuregulins (NRGs) in this process and show that a NRG receptor, ErbB4, is primarily expressed by polysialylated neural cell adhesion molecule immature neuroblasts but is also detected in a subset of GFAP(+) astroglial cells, ependymal cells, and Dlx2(+) precursors in the SVZ. Of the NRG ligands, both NRG1 and -2 are expressed by immature polysialylated neural cell adhesion molecule neuroblasts in the SVZ. NRG2 is also expressed by some of the GFAP(+) putative stem cells lining the ventricles. Infusion of exogenous NRG1 leads to rapid aggregation of Dlx2(+) cells in the SVZ and affects the initiation and maintenance of organized neuroblast migration from the SVZ toward the olfactory bulb. In contrast, the infusion of NRG2 increased the number of Sox2 and GFAP(+) precursors in the SVZ. An outcome of this NRG2 effect is an increase in the number of newly generated migrating neuroblasts in the rostral migratory stream and GABAergic interneurons in the olfactory bulb. The analysis of conditional null mice that lack NRG receptor, ErbB4, in the nervous system revealed that the observed activities of NRG2 require ErbB4 activation. These results indicate that different NRG ligands affect distinct populations of differentiating neural precursors in the neurogenic regions of the mature forebrain. Furthermore, these studies identify NRG2 as a factor capable of promoting SVZ proliferation, leading to the formation of new neurons in vivo.}, Author = {Ghashghaei, H. T. and Weber, Janet and Pevny, Larysa and Schmid, Ralf and Schwab, Markus H. and Lloyd, K. C. Kent and Eisenstat, David D. and Lai, Cary and Anton, E. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {03 Adult neurogenesis progenitor source;04 Adult neurogenesis factors}, Month = {2}, Nlm_Id = {7505876}, Number = {6}, Organization = {*University of North Carolina Neuroscience Center and the Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599.}, Pages = {1930-5}, Pii = {0510410103}, Pubmed = {16446434}, Title = {The role of neuregulin-ErbB4 interactions on the proliferation and organization of cells in the subventricular zone}, Uuid = {EC9D63C1-2ACB-4454-8500-E51901DD85D6}, Volume = {103}, Year = {2006}, url = {papers/Ghashghaei_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0510410103}} @article{Gheusi:2007, Abstract = {The mature brain needs to have flexible control over behavior in the face of ever-changing needs. It achieves this control through morphological and physiological changes at the level of molecules, spines, dendrites, and axons and through processes of adult neurogenesis, entire cells. The functional maturation of newly generated cells in the adult forebrain involves the expression of neurotransmitter receptors before synaptic activity and excitatory gamma-aminobutyric acid (GABAergic) influences prior to glutamatergic input. The production of new cells for incorporation into neural circuits that are already up and running gives rise to a unique situation that may require epigenetic regulation. However, once mature, new neurons must carve out a niche among more established cells to be useful. How do they survive and what are they used for? Recent studies have revealed that adult neurogenesis alters the olfactory bulb at all levels, from single cells to the network and system levels. It has also been suggested that cell turnover may be particularly beneficial for the processing of new information in dynamic networks. However, elucidating the functional meaning of adult neurogenesis must wait for the development of new paradigms to eliminate the pool of newly generated neurons but sparing the preexisting ones. Nevertheless, there is already considerable correlative evidence to indicate that adult neurogenesis is a plastic mechanism by which the performance of the brain can be optimized in a given environment.}, Author = {Gheusi, and Lledo,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0379-864X}, Journal = {Chem Senses}, Keywords = {01 Adult neurogenesis general;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8217190}, Organization = {Laboratory of Perception and Memory, Pasteur Institute, CNRS URA 2182, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France.}, Pii = {bjm012}, Pubmed = {17404148}, Title = {Control of Early Events in Olfactory Processing by Adult Neurogenesis}, Uuid = {59AE2ADC-C072-49E9-BCFD-1AB276302DF7}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/chemse/bjm012}} @article{Gheusi:2000, Abstract = {In adult rodents, neurons are continually generated in the subventricular zone of the forebrain, from where they migrate tangentially toward the olfactory bulb, the only known target for these neuronal precursors. Within the main olfactory bulb, they ascend radially into the granule and periglomerular cell layers, where they differentiate mainly into local interneurons. The functional consequences of this permanent generation and integration of new neurons into existing circuits are unknown. To address this question, we used neural cell adhesion molecule-deficient mice that have documented deficits in the migration of olfactory-bulb neuron precursors, leading to about 40\%size reduction of this structure. Our anatomical study reveals that this reduction is restricted to the granule cell layer, a structure that contains exclusively gamma- aminobutyric acid (GABA)ergic interneurons. Furthermore, mutant mice were subjected to experiments designed to examine the behavioral consequences of such anatomical alteration. We found that the specific reduction in the newly generated interneuron population resulted in an impairment of discrimination between odors. In contrast, both the detection thresholds for odors and short-term olfactory memory were unaltered, demonstrating that a critical number of bulbar granule cells is crucial only for odor discrimination but not for general olfactory functions.}, Author = {Gheusi, G. and Cremer, H. and McLean, H. and Chazal, G. and Vincent, J. D. and Lledo, P. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Olfactory Bulb/*cytology;Prosencephalon/metabolism;Memory, Short-Term;Neurons, Afferent/*metabolism;Animal;Mutation;02 Adult neurogenesis migration;Mice, Transgenic;Neural Cell Adhesion Molecules/*genetics;Smell/*genetics;Male;Support, Non-U.S. Gov't;Cell Division/genetics;B;Psychomotor Performance;Mice;Immunohistochemistry;Bromodeoxyuridine}, Number = {4}, Organization = {Centre National de la Recherche Scientifique, Institut Alfred Fessard, Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France.}, Pages = {1823-8.}, Title = {Importance of newly generated neurons in the adult olfactory bulb for odor discrimination}, Uuid = {E9590325-910B-44B8-B651-3A700F64B38C}, Volume = {97}, Year = {2000}, url = {../Data/Papers/text/dissertation/dissertation.pdf}} @article{Ghosh:1995, Abstract = {To identify molecules that regulate the transition of dividing neuroblasts to terminally differentiated neurons in the CNS, conditions have been developed that allow the neuronal differentiation of cortical precursor cells to be examined in vitro. In these cultures, the proliferation of undifferentiated precursor cells is controlled by basic fibroblast growth factor (bFGF). The proliferative effects of bFGF do not preclude the action of signals that promote differentiation, since addition of neurotrophin-3 (NT-3) antagonizes the proliferative effects of bFGF and enhances neuronal differentiation. In addition, blocking NT-3 function with neutralizing antibodies leads to a marked decrease in the number of differentiated neurons, without affecting the proliferation of cortical precursors or the survival of postmitotic cortical neurons. These observations suggest that bFGF and NT-3, by their distinct effects on cell proliferation and differentiation, are key regulators of neurogenesis in the CNS.}, Author = {Ghosh, A. and Greenberg, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Neuron}, Keywords = {Cerebral Cortex/*cytology;Rats;Phosphorylation;Cell Communication/physiology;Signal Transduction/*physiology;Neurotrophin 3;Animal;Fibroblast Growth Factor, Basic/*physiology;Support, Non-U.S. Gov't;Cell Division/physiology;Nerve Growth Factors/*physiology;Cells, Cultured/cytology;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Cell Differentiation/physiology;Immunohistochemistry;Neurons/cytology/metabolism;C-3}, Number = {1}, Organization = {Department of Microbiology and Molecular Genetics Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {89-103.}, Title = {Distinct roles for bFGF and NT-3 in the regulation of cortical neurogenesis}, Uuid = {F9E00BD6-1D98-4391-9B4A-E6F02F564171}, Volume = {15}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7619533}} @article{Ghoumari:2005, Abstract = {We have previously demonstrated that progesterone significantly increases the rate of myelination in organotypic slice cultures of 7-day-old rat and mouse cerebellum. Here, we show that progesterone (20muM) stimulates the proliferation of oligodendrocyte precursors in cultured cerebellar slices of 7-day-old rats. The steroid increased the number of pre-oligodendrocytes (NG2(+), O4(+)) and to some extent of oligodendrocyte precursors, corresponding to an earlier developmental stage (nestin(+), PDGFalphaR(+), NG2(+), O4(-)). Progesterone stimulated the proliferation of both NG2(+) and O4(+) cells as shown by increased double-immunolabeling with the cell proliferation marker Ki67. The mitogenic effect of progesterone was inhibited by the progesterone receptor antagonist mifepristone (10muM) and could not be mimicked by its GABA-active metabolite 3alpha,5alpha-tetrahydroprogesterone (allopregnanolone), even at the high concentration of 50muM. Results indicate that progesterone first strongly and transiently stimulates the proliferation of oligodendrocyte precursors, and that it may thereafter accelerate their maturation into myelinating oligodendrocytes. Although oligodendrocyte precursors may be a direct target for the actions of progesterone, their number may also be indirectly influenced by the effects of the steroid on neurons and microglial cells, since treatment of the cerebellar slices with progesterone enhanced staining of the neuronal cytoskeleton marker microtubule-associated protein-2 and increased the number of OX-42(+) microglia. A small percentage (about 0.1\%) of the NG2(+) cells transiently became OX-42(+) in response to progesterone. These results point to novel mechanisms by which progesterone may promote myelination in the CNS, specifically by stimulating the proliferation and maturation of oligodendrocyte precursors into myelinating oligodendrocytes.}, Author = {Ghoumari, and Baulieu, and Schumacher,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {11 Glia}, Month = {7}, Nlm_Id = {7605074}, Organization = {INSERM U488, Batiment Gregory Pincus, 80 rue du G{\'e}n{\'e}ral Leclerc, 94276 Bic\^{e}tre, France.}, Pii = {S0306-4522(05)00551-8}, Pubmed = {16054770}, Title = {Progesterone increases oligodendroglial cell proliferation in rat cerebellar slice cultures}, Uuid = {48A93EED-B2A2-4AC8-943F-57C001BD76FE}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2005.05.023}} @article{Giannetti:2000, Abstract = {Microgyria was experimentally induced by focal freezing lesions of the frontal cortex in newborn rats. Adult microgyric animals received cortical injections of biotinylated dextran amine combined with NMDA, in order to obtain a Golgi-like retrograde labeling of cortico-cortical association neurons. Injections were performed either rostrally or caudally to the microgyric lesion. Results demonstrate that long-range association projections traveling across the zone of the microgyric lesion arise mainly from infragranular layers. In normal animals the same projections originate both from supragranular and infragranular layers. The analysis of single basal dendrites of layer 2/3 in microgyric animals demonstrates a simplified branching pattern, with a number of end points lower than in control animals. Potential implications for microgyria-associated epilepsy are discussed.}, Author = {Giannetti, S. and Gaglini, P. and Di Rocco, F. and Di Rocco, C. and Granato, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Frontal Lobe;N-Methylaspartate;Disease Models, Animal;Research Support, Non-U.S. Gov't;Axonal Transport;Rats;Neural Pathways;Dextrans;Fluorescent Dyes;Rats, Wistar;Animals, Newborn;Biotin;Animals;Brain;24 Pubmed search results 2008;Cerebral Cortex;Neurons}, Medline = {20378179}, Month = {7}, Nlm_Id = {9100935}, Number = {10}, Organization = {Institute of Anatomy, Catholic University Medical School, Rome, Italy.}, Pages = {2185-9}, Pubmed = {10923667}, Title = {Organization of cortico-cortical associative projections in a rat model of microgyria}, Uuid = {B7B58DA5-D81A-4E2E-AFAC-EC54B987F887}, Volume = {11}, Year = {2000}} @article{Gianola:2002, Abstract = {Long-distance axon regeneration requires the activation of a specific set of neuronal growth-associated genes. Adult Purkinje cells fail to upregulate these molecules in response to axotomy and show extremely weak regenerative properties. Nevertheless, starting from several months after injury, transected Purkinje axons undergo spontaneous sprouting. Here, we asked whether long-term injured Purkinje cells acquire novel intrinsic growth properties that enable them to upregulate growth-associated genes and sustain axon regeneration. To test this hypothesis, we examined axon growth and cell body changes in adult rat Purkinje neurons following axotomy and implantation of embryonic neocortical tissue or Schwann cells into the injury track. Purkinje cells that survived over 6 months after injury/transplantation displayed profuse sprouting in the injured cerebellum and developed extensive networks of terminal branches into embryonic neocortical grafts. In addition, severed Purkinje axons exposed to these transplants 6 months after injury grew faster than their counterparts confronted with the same environment immediately after axotomy. Nevertheless, long-term injured Purkinje cells failed to regenerate stem neurites into Schwann cell grafts, and, under all experimental conditions, they did not upregulate growth-associated molecules, including c-Jun, GAP-43, SNAP-25, and NADPH-diaphorase. These results indicate that the long-term injured Purkinje cells remain unable to activate the gene program required to sustain axon regeneration and their plasticity is restricted to terminal arbor remodeling. We propose that the delayed growth of injured Purkinje cells reflects an adaptive phenomenon by which the severed axon stump develops a new terminal arbor searching for alternative connections with local partners.}, Author = {Gianola, Sara and Rossi, Ferdinando}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {GAP-43 Protein;Purkinje Cells;Animals;Brain Tissue Transplantation;Rats;Neuronal Plasticity;Neocortex;Axons;Neurites;Rats, Wistar;RNA, Messenger;Fetal Tissue Transplantation;Nerve Regeneration;In Situ Hybridization;Schwann Cells;Time;Animals, Newborn;Axotomy;Cerebellum;Cell Division;24 Pubmed search results 2008;Immunohistochemistry;Biological Markers;Research Support, Non-U.S. Gov't}, Medline = {22088426}, Month = {7}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Neuroscience and Rita Levi Montalcini Center for Brain Repair, University of Turin, Turin, Italy.}, Pages = {25-40}, Pii = {S0014488602979240}, Pubmed = {12093080}, Title = {Long-term injured purkinje cells are competent for terminal arbor growth, but remain unable to sustain stem axon regeneration}, Uuid = {2ED98C73-4B9A-415D-807F-FB9D783CD214}, Volume = {176}, Year = {2002}} @article{Gibson:2003, Abstract = {Periventricular leukomalacia (PVL) is either a diffuse or cystic lesion of the periventricular white matter that leaves the overlying cortical grey matter largely intact. It is believed to result from hypoxia occurring pre- or perinatally and is a major cause of cerebral palsy. We have modelled PVL in rats comparing the effects of discrete injections of 3-nitropropionic acid (3-NP), a mitochondrial toxin, ibotenic acid (IBA), a glutamate analogue, or saline into the sub-cortical white matter on postnatal day 7 (P7). Following recovery times ranging from 3 days to 4 weeks, forebrain sections were Nissl stained or immunostained for Bax, cJun, calbindin (CB), parvalbumin (PV) or non-phosphorylated neurofilaments (NPNF). Compared to saline injections, ibotenic acid caused large lesions of both grey and white matter not characteristic of periventricular leukomalacia. 3-Nitropropionic acid injections caused small focal lesions restricted to the sub-cortical white matter. 3-Nitropropionic acid treatment initially increased expression of the apoptosis promoting proteins Bax and cJun, as well as non-phosphorylated neurofilaments in cortical layer V overlying the injection site. Non-phosphorylated neurofilament expression distal to the lesion was decreased representing a loss of cortical axons, but persisted and even increased with time within the cortex, demonstrating persistence of the parent cell bodies and local sprouting of neurites. There were significantly fewer calbindin and parvalbumin positive neurones in the motor cortex (MC) side ipsilateral to the 3-nitropropionic acid injection compared to the contralateral side. These persistent differences in expression of activity sensitive calcium binding proteins suggest alterations in local cortical circuitry without substantial loss of grey matter as is characteristic of periventricular leukomalacia. Changes in expression of Bax, cJun and non-phosphorylated neurofilaments during normal development are also described.}, Author = {Gibson, Claire L. and Clowry, Gavin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0736-5748}, Journal = {Int J Dev Neurosci}, Keywords = {Propionic Acids;Animals;Humans;Rats;Comparative Study;21 Epilepsy;Apoptosis;Nitro Compounds;Axons;Leukomalacia, Periventricular;Reference Values;Rats, Wistar;Disease Models, Animal;Ibotenic Acid;Motor Cortex;Animals, Newborn;21 Neurophysiology;Neurons;Infant, Newborn;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {22666659}, Month = {6}, Nlm_Id = {8401784}, Number = {4}, Organization = {Brain Development, Plasticity and Repair Group, School of Clinical Medical Sciences (Child Health), University of Newcastle upon Tyne, UK.}, Pages = {171-82}, Pii = {S0736574803000418}, Pubmed = {12781784}, Title = {The effect on motor cortical neuronal development of focal lesions to the sub-cortical white matter in the neonatal rat: a model for periventricular leukomalacia}, Uuid = {5C551320-73C7-4670-92EA-057D1E575CD2}, Volume = {21}, Year = {2003}} @article{Gibson:1999, Abstract = {Inhibitory interneurons are critical to sensory transformations, plasticity and synchronous activity in the neocortex. There are many types of inhibitory neurons, but their synaptic organization is poorly understood. Here we describe two functionally distinct inhibitory networks comprising either fast-spiking (FS) or low-threshold spiking (LTS) neurons. Paired-cell recordings showed that inhibitory neurons of the same type were strongly interconnected by electrical synapses, but electrical synapses between different inhibitory cell types were rare. The electrical synapses were strong enough to synchronize spikes in coupled interneurons. Inhibitory chemical synapses were also common between FS cells, and between FS and LTS cells, but LTS cells rarely inhibited one another. Thalamocortical synapses, which convey sensory information to the cortex, specifically and strongly excited only the FS cell network. The electrical and chemical synaptic connections of different types of inhibitory neurons are specific, and may allow each inhibitory network to function independently. 0028-0836 Journal Article}, Author = {Gibson, J. R. and Beierlein, M. and Connors, B. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Nature}, Keywords = {Gap Junctions/physiology;Electrophysiology;Animals;In Vitro;Axons/physiology;Rats;Rats, Sprague-Dawley;Thalamus/physiology;Synapses/physiology;M;Action Potentials;Nerve Net/cytology/*physiology;Synaptic Transmission/physiology;*Neural Inhibition;Somatosensory Cortex/cytology/*physiology;Support, U.S. Gov't, P.H.S.;18 Classic Neuroanatomy Physiology;Interneurons/*physiology}, Number = {6757}, Organization = {Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.}, Pages = {75-9}, Pubmed = {10573419}, Title = {Two networks of electrically coupled inhibitory neurons in neocortex}, Uuid = {C1580028-52EB-4644-AC1A-0262FD895031}, Volume = {402}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10573419}} @article{Gifford:2003, Abstract = {The retroviral capacity for integration into the host genome can give rise to endogenous retroviruses (ERVs): retroviral sequences that are transmitted vertically as part of the host germ line, within which they may continue to replicate and evolve. ERVs represent both a unique archive of ancient viral sequence information and a dynamic component of host genomes. As such they hold great potential as informative markers for studies of both virus evolution and host genome evolution. Numerous novel ERVs have been described in recent years, particularly as genome sequencing projects have advanced. This review discusses the evolution of ERV lineages, considering the processes by which ERV distribution and diversity is generated. The diversity of ERVs isolated so far is summarised in terms of both their distribution across host taxa, and their relationships to recognised retroviral genera. Finally the relevance of ERVs to studies of genome evolution, host disease and viral ecology is considered, and recent findings discussed.}, Author = {Gifford, Robert and Tristem, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0920-8569}, Journal = {Virus Genes}, Keywords = {15 ERVs retroelements;Endogenous Retroviruses;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Evolution, Molecular;15 Retrovirus mechanism;Variation (Genetics);Humans;Animals;Vertebrates;review}, Medline = {22759165}, Month = {5}, Nlm_Id = {8803967}, Number = {3}, Organization = {Department of Biological Sciences, Imperial College, Silwood Park, Buckhurst Road, Ascot Berkshire, SL5 7PY, UK.}, Pages = {291-315}, Pii = {5127076}, Pubmed = {12876457}, Title = {The evolution, distribution and diversity of endogenous retroviruses}, Uuid = {28AD1074-EF57-4816-8C33-AD09D5CD10BB}, Volume = {26}, Year = {2003}} @article{Gilja:2007, Abstract = {The greater spatial coherence of local field potentials (LFPs) compared with that of spiking activity has been attributed to frequency-dependent propagation of signals through the cortical medium. However, in this issue of Neuron, Logothetis and colleagues show that signal propagation within cortex is largely unbiased across different frequencies, thus suggesting a more functional and interpretable basis of LFP coherence.}, Author = {Gilja, Vikash and Moore, Tirin}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Axons;Perception;24 Pubmed search results 2008;21 Neurophysiology;Action Potentials;Neural Pathways;Evoked Potentials;comment;Synaptic Transmission;Animals;Humans;Cerebral Cortex;Neurons;news}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Computer Science, Stanford University, Stanford, CA 94305, USA.}, Pages = {684-6}, Pii = {S0896-6273(07)00624-1}, Pubmed = {17785175}, Title = {Electrical signals propagate unbiased in cortex}, Uuid = {B99F4800-81B6-45E7-8F77-EACE94B36A32}, Volume = {55}, Year = {2007}, url = {papers/Gilja_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.08.012}} @article{Gilmore:2001, Abstract = {The adult mammalian cerebral cortex arises from a complex series of neuronal migrations. The primitive layer known as the preplate is split into an outer marginal zone and an inner subplate by invading cortical plate neurons in an "inside-out"pattern of layering with respect to time of neuronal origin. In cyclin-dependent kinase 5 (Cdk5)-deficient mice (cdk5(-/-)), the earliest born cortical neurons split the preplate, but later born neurons arrest below the subplate, resulting in an ectopic "outside-in"layer of neurons normally destined for layers II-V. We have pursued this analysis in cdk5(-/-) <-->wild-type chimeric mice coupled with experiments in cell culture. In vitro migration assays show no difference in migrational ability between embryonic cdk5(-/-) and wild-type neurons. In cdk5(-/-) chimeras, layers I and VI are made up of both mutant and wild-type genotype neurons, whereas layers II-V contain predominantly wild-type cells. In addition, a thin layer of neurons is found below layer VI, made up of cdk5(-/-) cells; bromodeoxyuridine labeling suggests that these neurons were destined for layers II-V. Scattered cdk5(-/-) cells are found throughout layers II-V, but these neurons are always found to be GABAergic. The findings suggest that Cdk5 is not required for migration of either the deepest cortical plate neurons or the GABAergic neurons from the ganglionic eminences. The migration of layer II-V pyramidal neurons, however, is intrinsically blocked by Cdk5 deficiency, thus suggesting that different neuronal cell types use distinct mechanisms of migration. 1529-2401 Journal Article}, Author = {Gilmore, E. C. and Herrup, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurosci}, Keywords = {Neocortex/cytology/*embryology/metabolism;Animals;Cyclin-Dependent Kinases/deficiency/genetics/*metabolism;Neurons/cytology/*metabolism;Cells, Cultured;Chimera;Cell Movement/*physiology;Female;Stem Cells/cytology;Cell Count;gamma-Aminobutyric Acid/*metabolism;Interneurons/cytology/metabolism;Mice, Inbred C57BL;Male;H abstr;Support, U.S. Gov't, P.H.S.;Purkinje Cells/cytology;Mice;Immunohistochemistry;Bromodeoxyuridine;12 Interneuron development}, Number = {24}, Organization = {Department of Neurosciences, School of Medicine, Case Western Reserve University, and Alzheimer Research Laboratory, University Hospitals of Cleveland, Cleveland, Ohio 44106.}, Pages = {9690-700}, Pubmed = {11739578}, Title = {Neocortical cell migration: GABAergic neurons and cells in layers I and VI move in a cyclin-dependent kinase 5-independent manner}, Uuid = {299F7385-C835-4C65-B6AF-6D6A72E372D4}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11739578}} @article{Gimsa:2000, Abstract = {Neuroinflammation in the course of multiple sclerosis and experimental autoimmune encephalomyelitis results in demyelination and, recently demonstrated, axonal loss. Invading neuroantigen specific T cells are the crucial cellular elements in these processes. Here we demonstrate that invasion of activated T cells induces a massive microglial attack on myelinated axons in entorhinal-hippocampal slice cultures. Flow cytometry analysis of activation markers revealed that the activation state of invading MBP-specific T cells was significantly lower in comparison to PMA-activated T cells. Moreover, MBP-specific T cells showed a significantly lower secretion of IFN-gamma. Conversely, MBP-specific T cells displayed a significantly higher potential to trigger activation of microglial cells, i.e. upregulation of MHC class II and ICAM-1 expression, and, most importantly, microglial phagocytosis of pre-traced axons. Our data suggest that this was mediated via specific cellular interactions of T cells and microglial cells since IFN-gamma alone was not sufficient to induce axonal damage while such damage was apparent in response to TNF-alpha which is released by activated microglial cells. TNF-alpha secretion by both T cell populations was negligible. Thus, MBP-specific T cells which invade nervous tissue in the course of neuroinflammation are more effective in axon-damaging recruiting microglial cells than activated T cells of other specificities.}, Author = {Gimsa, U. and Peter, S. V. and Lehmann, K. and Bechmann, I. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {1015-6305}, Journal = {Brain Pathol}, Keywords = {Cell Survival;T-Lymphocytes;Tumor Necrosis Factor;Animals;Phagocytosis;Research Support, Non-U.S. Gov't;Intercellular Adhesion Molecule-1;Tumor Necrosis Factor-alpha;Microglia;Interferon Type II;Entorhinal Cortex;Lymphocyte Activation;Hippocampus;Axons;Not relevant;11 Glia;Organ Culture Techniques;Support, Non-U.S. Gov't;Mice, Inbred Strains;Neurons;Mice;Organ Culture;Histocompatibility Antigens Class II;Cytokines}, Medline = {20340164}, Month = {7}, Nlm_Id = {9216781}, Number = {3}, Organization = {Department of Cell and Neurobiology, Institute of Anatomy, Humboldt-University Clinic Charit{\'e}, Berlin, Germany. ulrike.gimsa\@charite.de}, Pages = {365-77}, Pubmed = {10885655}, Title = {Axonal damage induced by invading T cells in organotypic central nervous system tissue in vitro: involvement of microglial cells}, Uuid = {8DFF539F-01EC-4EA8-BDA8-BAA20ADFBB21}, Volume = {10}, Year = {2000}} @article{Giordana:1994, Abstract = {The non-astrocytic cells which proliferate in the rat brain after the induction of an area of necrosis have been characterized and counted by means of combined in vivo bromodeoxyuridine (BrdU) administration and immunohistochemical demonstration of glial fibrillary acid protein (GFAP), vimentin, Ricinus communis agglutinin 120 (RCA-1), Griffonia simplicifolia B4 isolectin (GSI-B4), keratan sulphate (KS), carbonic anhydrase C (CA.C), transferrin (TF) and ferritin. Two days after the injury, 7.5\%of the proliferating cells were GFAP-positive reactive astrocytes, 5.7\%were RCA-1-positive cells and 17.4\%were GSI-B4-positive cells. Lectin-binding cells had the microscopic and ultrastructural aspects of microglia; they proliferated around the needle track and in the corpus callosum. Microglia represented a large fraction of the proliferating cells. Evidence is presented for the origin of at least a proportion of perilesional astrocytes and microglia from the periventricular matrix, and of microglia from blood precursors. Other non-proliferating microglia cells transiently appeared in the normal brain around the wound, in agreement with the existence of two different microglia cell populations reacting with different modalities to an area of necrosis.}, Author = {Giordana, M. T. and Attanasio, A. and Cavalla, P. and Migheli, A. and Vigliani, M. C. and Schiffer, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Rats, Inbred F344;Rats;Antibodies, Monoclonal;Astrocytes;Immunohistochemistry;Cell Division;Not relevant;11 Glia;Microglia;Microscopy, Immunoelectron;Animals;Bromodeoxyuridine;Brain Injuries}, Medline = {94352525}, Month = {4}, Nlm_Id = {7609829}, Number = {2}, Organization = {Second Department of Neurology, University of Turin, Italy.}, Pages = {163-74}, Pubmed = {8072646}, Title = {Reactive cell proliferation and microglia following injury to the rat brain}, Uuid = {973E4AA5-F58E-47EE-8804-FA2DE30FAAB2}, Volume = {20}, Year = {1994}} @article{Gitler:2004, Abstract = {The functions of synapsins were examined by characterizing the phenotype of mice in which all three synapsin genes were knocked out. Although these triple knock-out mice were viable and had normal brain anatomy, they exhibited a number of behavioral defects. Synaptic transmission was altered in cultured neurons from the hippocampus of knock-out mice. At excitatory synapses, loss of synapsins did not affect basal transmission evoked by single stimuli but caused a threefold increase in the rate of synaptic depression during trains of stimuli. This suggests that synapsins regulate the reserve pool of synaptic vesicles. This possibility was examined further by measuring synaptic vesicle density in living neurons transfected with green fluorescent protein-tagged synaptobrevin 2, a marker of synaptic vesicles. The relative amount of fluorescent synaptobrevin was substantially lower at synapses of knock-out neurons than of wild-type neurons. Electron microscopy also revealed a parallel reduction in the number of vesicles in the reserve pool of vesicles >150 nm away from the active zone at excitatory synapses. Thus, synapsins are required for maintaining vesicles in the reserve pool at excitatory synapses. In contrast, basal transmission at inhibitory synapses was reduced by loss of synapsins, but the kinetics of synaptic depression were unaffected. In these terminals, there was a mild reduction in the total number of synaptic vesicles, but this was not restricted to the reserve pool of vesicles. Thus, synapsins maintain the reserve pool of glutamatergic vesicles but regulate the size of the readily releasable pool of GABAergic vesicles.}, Author = {Gitler, Daniel and Takagishi, Yoshiko and Feng, Jian and Ren, Yong and Rodriguiz, Ramona M. and Wetsel, William C. and Greengard, Paul and Augustine, George J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:39:47 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, n.i.h., extramural ;Animals;Synapses;Evoked Potentials;Neuronal Plasticity;Phenotype;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Synaptic Vesicles;Neurotransmitter Agents;Brain;Hippocampus;comparative study ;research support, non-u.s. gov't ;Action Potentials;Learning;Mice, Knockout;21 Neurophysiology;Synapsins;Multigene Family;Mice;24 Pubmed search results 2008;Neural Inhibition}, Month = {12}, Nlm_Id = {8102140}, Number = {50}, Organization = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.}, Pages = {11368-80}, Pii = {24/50/11368}, Pubmed = {15601943}, Title = {Different presynaptic roles of synapsins at excitatory and inhibitory synapses}, Uuid = {3AD28327-A565-4C32-98BD-B5521BD9E157}, Volume = {24}, Year = {2004}, url = {papers/Gitler_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3795-04.2004}} @article{Giulian:1986, Abstract = {Ameboid microglia are isolated from the cerebral tissue of neonatal rat by selective cell adhesion to plastic. Histochemical markers show that the microglial preparations are homogeneous (95 +/- 3\%) and represent a 10\%yield from starting cultures. Isolated ameboid microglia contain nonspecific esterase activity, the macrophage surface antigens MAC-1 and MAC-3, and acetylated low-density lipoprotein receptors. Ameboid cells have functional properties similar to those of macrophages, including the ability to engulf 5 micron latex beads, to secrete Interleukin-1 (IL-1) and to release superoxide anion. Unlike monocytes and adherent spleen cells, ameboid microglia do not show peroxidase activity by histochemical stain. Unlike resident peritoneal macrophages, ameboid microglia proliferate in vitro. Scanning electron microscopy shows that ameboid cells have short, spinous processes that can be distinguished from the ruffled surfaces of body macrophages. Our observations suggest that ameboid microglia are a distinct class of mononuclear phagocytic cells. Retinoic acid and dimethyl sulfoxide, agents known to accelerate differentiation in vitro, stimulate ameboid cells to develop thin processes several hundred microns in length. These "process-bearing" microglia eventually lose the capacity to engulf latex beads and to proliferate. They also show reductions in nonspecific esterase activity and in the binding of acetylated low-density lipoprotein. We suggest that in vitro ameboid microglia differentiate into nonphagocytic cells similar to ramified microglia found in normal adult brain. The isolation techniques described here provide the opportunity to study the composition and function of different microglial subpopulations during the development of the CNS.}, Author = {Giulian, D. and Baker, T. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Microscopy, Phase-Contrast;Microscopy, Electron, Scanning;Animals;Cell Separation;Macrophages;Rats;Brain;Oligodendroglia;Esterases;Superoxides;Not relevant;11 Glia;Animals, Newborn;Histocytochemistry;Support, Non-U.S. Gov't;Neuroglia;Interleukin-1;Support, U.S. Gov't, P.H.S.;Spleen}, Medline = {86307003}, Month = {8}, Nlm_Id = {8102140}, Number = {8}, Pages = {2163-78}, Pubmed = {3018187}, Title = {Characterization of ameboid microglia isolated from developing mammalian brain}, Uuid = {3B91C779-CB93-4B92-93FE-9FDE8AF1B7F1}, Volume = {6}, Year = {1986}, url = {papers/Giulian_JNeurosci1986.pdf}} @article{Giulian:1989, Abstract = {We monitor cellular responses to a penetrating wound in the cerebral cortex of adult rat during the first weeks after injury. Two classes of activated mononuclear phagocytes containing acetylated low-density lipoprotein (ac-LDL) receptors appear within hours at the wound site. One type of cell surrounding the lesion edge had thin, delicate processes and is identical in appearance to ramified microglia found in developing brain. Within the lesion, round cells are recognized as blood-borne macrophages when labeled by intravenous injection of carbon particles. Thus, both process-bearing reactive microglia and invading macrophages respond to brain trauma. The greatest number of ac-LDL(+) or nonspecific esterase(+) mononuclear phagocytes appears 2 days after injury within the wound site and are associated with a peak production of the cytokine interleukin-1 (IL-1). Because intracerebral infusion of IL-1 is known to stimulate astrogliosis and neovascularization (Giulian et al., 1988), we examine the time course of injury-induced reactive astrogliosis and angiogenesis. A 5-fold increase in the number of reactive astroglia is found at 3 d and a marked neovascularization at 5 d after injury. During the first week, mononuclear phagocytes engulf particles and clear them from the wound site either by migrating to the brain surface or by entering newly formed brain vasculature. To investigate further the role of reactive brain mononuclear phagocytes in CNS injury, we use drugs to inhibit trauma-induced inflammation. When applied in vivo, chloroquine or colchicine reduce the number of mononuclear phagocytes in damaged brain, help to block reactive astrogliosis and neovascularization, and slow the rate of debris clearance from sites of traumatic injury. In contrast, the glucocorticoid dexamethasone neither reduces the number of brain inflammatory cells nor hampers such responses as phagocytosis, astrogliosis, neovascularization, or debris clearance in vivo. Our observations show that mononuclear phagocytes play a major role in wound healing after CNS trauma with some events controlled by secretion of cytokines. Moreover, certain classes of immunosuppressive drugs may be useful in the treatment of acute brain injury.}, Author = {Giulian, D. and Chen, J. and Ingeman, J. E. and George, J. K. and Noponen, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Wound Healing;Astrocytes;Animals;Encephalitis;Rats;Colchicine;Rats, Inbred Strains;Wounds, Penetrating;11 Glia;Phagocytes;Chloroquine;Microspheres;Research Support, U.S. Gov't, P.H.S.;Neovascularization, Pathologic;Brain Injuries;Cerebral Cortex;Gliosis;Dexamethasone}, Medline = {90079552}, Month = {12}, Nlm_Id = {8102140}, Number = {12}, Organization = {Department of Neurology, Baylor College of Medicine, Houston, Texas 77031.}, Pages = {4416-29}, Pubmed = {2480402}, Title = {The role of mononuclear phagocytes in wound healing after traumatic injury to adult mammalian brain}, Uuid = {614F2A40-6849-4A86-8987-A7E1F726A4C7}, Volume = {9}, Year = {1989}} @article{Givogri:2006, Abstract = {The postnatal subventricular zone (SVZ) is a niche for continuous neurogenesis in the adult brain and likely plays a fundamental role in self-repair responses in neurodegenerative conditions. Maintenance of the pool of neural stem cells within this area depends on cell-cell communication such as that provided by the Notch signaling pathway. Notch1 receptor mRNA has been found distributed in different areas of the postnatal brain including the SVZ. Although the identity of Notch1-expressing cells has been established in the majority of these areas, it is still unclear what cell types within the SVZ are expressing components of this pathway. Here we demonstrate that most of expression of Notch1 in the adult SVZ occurs in polysialylated neural cell adhesion molecule (PSA-NCAM)-positive neural precursors and in glial fibrillary acidic protein-positive SVZ astrocytes. Notch1 was also found in PSA-NCAM-positive neuroblasts located within the rostral migratory stream (RMS) but much less in those that have reached the olfactory bulb. We show that two of the naturally occurring Notch1 activators, Jagged1 and Delta1, are also expressed in the SVZ and within the RMS in the adult mouse brain. Finally, using a model of cortical stab wound, we show that the astrogliogenic response of the SVZ to injury is accompanied by activation of the Notch pathway.}, Author = {Givogri, Maria I. and de Planell, Maria and Galbiati, Francesca and Superchi, Daniela and Gritti, Angela and Vescovi, Angelo and de Vellis, Jean and Bongarzone, Ernesto R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {24 Pubmed search results 2008}, Nlm_Id = {7809375}, Number = {1-2}, Organization = {Laboratory for Gene Therapy of Neurodegenerative Disorders, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy. givogri.maria\@hsr.it}, Pages = {81-91}, Pii = {DNE20060281_2081}, Pubmed = {16508306}, Title = {Notch signaling in astrocytes and neuroblasts of the adult subventricular zone in health and after cortical injury}, Uuid = {73022267-5C23-4F7E-A3E8-1932ADAEE50A}, Volume = {28}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000090755}} @article{Gleeson:1998, Abstract = {X-linked lissencephaly and "double cortex" are allelic human disorders mapping to Xq22.3-Xq23 associated with arrest of migrating cerebral cortical neurons. We identified a novel 10 kb brain-specific cDNA interrupted by a balanced translocation in an XLIS patient that encodes a novel 40 kDa predicted protein named Doublecortin. Four double cortex/X-linked lissencephaly families and three sporadic double cortex patients show independent doublecortin mutations, at least one of them a de novo mutation. Doublecortin contains a consensus Abl phosphorylation site and other sites of potential phosphorylation. Although Doublecortin does not contain a kinase domain, it is homologous to the amino terminus of a predicted kinase protein, indicating a likely role in signal transduction. Doublecortin, along with the newly characterized mDab1, may define an Abl-dependent pathway regulating neuronal migration.}, Author = {Gleeson, J. G. and Allen, K. M. and Fox, J. W. and Lamperti, E. D. and Berkovic, S. and Scheffer, I. and Cooper, E. C. and Dobyns, W. B. and Minnerath, S. R. and Ross, M. E. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Microtubule-Associated Proteins;Signal Transduction;10 Development;Chromosome Fragility;Syndrome;Base Sequence;Sequence Homology, Amino Acid;Humans;Proteins;Brain;Epilepsy;Mutation;Protein-Serine-Threonine Kinases;Genes;Translocation, Genetic;Neuropeptides;Research Support, U.S. Gov't, P.H.S.;X Chromosome;Cerebral Cortex;Sex Chromosome Aberrations;Family Health;DNA, Complementary;Chromosome Mapping;Molecular Sequence Data;Amino Acid Sequence;Research Support, Non-U.S. Gov't}, Medline = {98149344}, Month = {1}, Nlm_Id = {0413066}, Number = {1}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.}, Pages = {63-72}, Pubmed = {9489700}, Title = {Doublecortin, a brain-specific gene mutated in human X-linked lissencephaly and double cortex syndrome, encodes a putative signaling protein}, Uuid = {CB455028-6D11-11DA-A4FE-000D9346EC2A}, Volume = {92}, Year = {1998}, url = {papers/Gleeson_Cell1998.pdf}} @article{Gleeson:1999, Abstract = {Doublecortin (DCX) is required for normal migration of neurons into the cerebral cortex, since mutations in the human gene cause a disruption of cortical neuronal migration. To date, little is known about the distribution of DCX protein or its function. Here, we demonstrate that DCX is expressed in migrating neurons throughout the central and peripheral nervous system during embryonic and postnatal development. DCX protein localization overlaps with microtubules in cultured primary cortical neurons, and this overlapping expression is disrupted by microtubule depolymerization. DCX coassembles with brain microtubules, and recombinant DCX stimulates the polymerization of purified tubulin. Finally, overexpression of DCX in heterologous cells leads to a dramatic microtubule phenotype that is resistant to depolymerization. Therefore, DCX likely directs neuronal migration by regulating the organization and stability of microtubules.}, Author = {Gleeson, J. G. and Lin, P. T. and Flanagan, L. A. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Microtubule-Associated Proteins;Purkinje Cells;Rats, Long-Evans;Animals;Cells, Cultured;Rats;Humans;Phosphoproteins;Tubulin;Mitosis;Colchicine;Cell Movement;RNA, Messenger;Neuropeptides;Microtubules;In Situ Hybridization;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Cerebral Cortex;Neurons;Blotting, Western;Mice;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {99325520}, Month = {6}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.}, Pages = {257-71}, Pii = {S0896-6273(00)80778-3}, Pubmed = {10399933}, Title = {Doublecortin is a microtubule-associated protein and is expressed widely by migrating neurons}, Uuid = {AD8AFBA3-A3E5-11DA-AB00-000D9346EC2A}, Volume = {23}, Year = {1999}, url = {papers/Gleeson_Neuron1999.pdf}} @article{Gleeson:2007, Abstract = {Conductance-based neuronal network models can help us understand how synaptic and cellular mechanisms underlie brain function. However, these complex models are difficult to develop and are inaccessible to most neuroscientists. Moreover, even the most biologically realistic network models disregard many 3D anatomical features of the brain. Here, we describe a new software application, neuroConstruct, that facilitates the creation, visualization, and analysis of networks of multicompartmental neurons in 3D space. A graphical user interface allows model generation and modification without programming. Models within neuroConstruct are based on new simulator-independent NeuroML standards, allowing automatic generation of code for NEURON or GENESIS simulators. neuroConstruct was tested by reproducing published models and its simulator independence verified by comparing the same model on two simulators. We show how more anatomically realistic network models can be created and their properties compared with experimental measurements by extending a published 1D cerebellar granule cell layer model to 3D.}, Author = {Gleeson, Padraig and Steuber, Volker and Silver, R. Angus}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {24 Pubmed search results 2008;23 Technique}, Month = {4}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Physiology, University College London, Gower Street, London WC1E 6BT, United Kingdom.}, Pages = {219-35}, Pii = {S0896-6273(07)00248-6}, Pubmed = {17442244}, Title = {neuroConstruct: A Tool for Modeling Networks of Neurons in 3D Space}, Uuid = {B7854664-01C2-45F7-8A4E-B4B465AFA5DA}, Volume = {54}, Year = {2007}, url = {papers/Gleeson_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.03.025}} @article{Glezer:2006, Abstract = {Regarded as a damaging reaction, innate immune response can either improve or worsen brain outcome after injury. Hence, inflammatory molecules might modulate cell susceptibility or healing events. The remyelination that follows brain lesions is dependent on the recruitment of oligodendrocyte progenitor cells (OPCs) and expression of genes controlling differentiation and myelin production, such as Olig1 and Olig2 bHLH transcription factors. We aimed to determine how innate immunity affects these processes. Here we report that lipopolysaccharide (LPS) infusion triggered OPC reactivity. Acute inflammation changed the distribution of Olig1- and Olig2-expressing cells following chemical demyelination, enhanced reappearance of transcription signals linked to remyelination and rapidly cleared myelin debris. Although cells expressing Olig1, Olig2, and proteolipid protein were attracted to demyelinated sites in the course of chronic inflammation, myelin loss was not associated with the effects of inflammation on OPC reactivity. In addition, the beneficial properties of brain immunity are broadened to an aggressive model of injury, wherein LPS through Toll-like receptor 4 (TLR4) reduced surfactant-mediated damage while anti-inflammatory treatment enlarged the lesion. In conclusion, TLR4 activation in microglia is a powerful mechanism for improving repair at the remyelination level and protecting the cerebral tissue in presence of agents with strong cytolytic properties.}, Author = {Glezer, and Lapointe, and Rivest,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {11 Glia}, Month = {2}, Nlm_Id = {8804484}, Pii = {05-5234fje}, Pubmed = {16464958}, Title = {Innate immunity triggers oligodendrocyte progenitor reactivity and confines damages to brain injuries}, Uuid = {856C4583-1B47-449C-AA17-DA97384D0B73}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.05-5234fje}} @article{Gloveli:2005, Abstract = {As a structure involved in learning and memory, the hippocampus functions as a network. The functional differentiation along the longitudinal axis of the hippocampus is poorly demarcated in comparison with the transverse axis. Using patch clamp recordings in conjunction with post hoc anatomy, we have examined the pattern of connectivity and the functional differentiation along the long axis of the hippocampus. Here, we provide anatomical and physiological evidence that the prominent rhythmic network activities of the hippocampus, the behavior-specific gamma and theta oscillations, are seen predominantly along the transverse and longitudinal axes respectively. This orthogonal relationship is the result of the axonal field trajectories and the consequential interaction of the principal cells and major interneuron subtypes involved in generating each rhythm. Thus, the axonal arborization patterns of hippocampal inhibitory cells may represent a structural framework for the spatiotemporal distribution of activity observed within the hippocampus.}, Author = {Gloveli, Tengis and Dugladze, Tamar and Rotstein, Horacio G. and Traub, Roger D. and Monyer, Hannah and Heinemann, Uwe and Whittington, Miles A. and Kopell, Nancy J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008;Electroencephalography;research support, non-u.s. gov't;Theta Rhythm;21 Neurophysiology;Hippocampus;Pyramidal Cells;Mice, Inbred C57BL;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;Interneurons;research support, u.s. gov't, p.h.s.;Animals;Mice;Nerve Net;Patch-Clamp Techniques;21 Cortical oscillations}, Month = {9}, Nlm_Id = {7505876}, Number = {37}, Organization = {Institute of Neurophysiology, Charit{\'e}-Universit{\"a}tsmedizin Berlin, Tucholskystrasse 2, 10117 Berlin, Germany. tengis.gloveli\@charite.de}, Pages = {13295-300}, Pii = {0506259102}, Pubmed = {16141320}, Title = {Orthogonal arrangement of rhythm-generating microcircuits in the hippocampus}, Uuid = {B59C66E9-172F-4C45-AEAC-4EF9B14E11E0}, Volume = {102}, Year = {2005}, url = {papers/Gloveli_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0506259102}} @article{Godukhin:2002, Abstract = {Repeated exposures of rat hippocampal slices to short episodes of hypoxia induce a sustained decrease in the threshold of the development of stimulus-evoked epileptiform discharges in CA1 pyramidal neurons. We have previously demonstrated that the K(+)(o)-induced hyperexcitability required functional L-type voltage-dependent Ca(2+) channels and NMDA-receptors, but was independent of AMPA/kainate-receptor activation. As hypoxia/ischaemia can lead to increased K(+)(o), the epileptiform activity observed after exposure to these challenges could also result from high K(+)(o). The purpose of this study was: (i) to determine whether ionotropic glutamate receptors and L-type Ca(2+) channels are involved in the development of epileptiform activity induced by repeated exposures of hippocampal slices to hypoxia; and (ii) to compare the properties of hypoxia- and high K(+)(o)-induced hyperexcitability. Population spike of presynaptic fibres with field excitatory postsynaptic potential from the stratum radiatum, and population spike of CA1 pyramidal neurons from the stratum pyramidale, were recorded simultaneously in the CA1 area of rat hippocampal slices in response to electrical stimulation of the Schaffer collateral/commissural fibres. Repeated, brief hypoxic episodes induced a sustained decrease in the threshold for development of evoked epileptiform discharges that was associated with long-term potentiation of the CA3-CA1 synapses, but without EPSP-spike potentiation (i.e. in contrast to high K(+)(o)-induced hyperexcitability). The selective antagonist of NMDA receptors, D-APV (25 microM), and the selective blocker of L-type Ca(2+) channels, nifedipine (10 microM) depressed the development of hypoxia-induced hyperexcitability. However, in contrast to high K(+)(o)-induced hyperexcitability, hypoxia-induced hyperexcitability was also blocked by the AMPA/kainite-receptor antagonist, CNQX (5 microM). The present findings confirm that repeated, brief episodes of hypoxia, like exposure to high extracellular K(+), can induce a pro-epileptic state in the CA1 neuronal network, but that the mechanisms leading to hyperexcitability are different for the two stimuli.}, Author = {Godukhin, O. and Savin, A. and Kalemenev, S. and Levin, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0028-3908}, Journal = {Neuropharmacology}, Keywords = {Excitatory Amino Acid Antagonists;Receptors, Glutamate;Long-Term Potentiation;Animals;Research Support, Non-U.S. Gov't;In Vitro;Rats;Comparative Study;21 Epilepsy;Cell Hypoxia;Hippocampus;Rats, Wistar;Male;Neurons;21 Neurophysiology;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;Calcium Channels, L-Type;Excitatory Postsynaptic Potentials}, Medline = {21953708}, Month = {3}, Nlm_Id = {0236217}, Number = {4}, Organization = {Institute of Theoretical and Experimental Biophysics of the Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia. godukhim\@hotmail.com}, Pages = {459-66}, Pii = {S0028390802000059}, Pubmed = {11955517}, Title = {Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: involvement of ionotropic glutamate receptors and L-type Ca(2+) channels}, Uuid = {DB9F98AD-D25E-4FCD-89CF-34351C01E7B2}, Volume = {42}, Year = {2002}} @article{Goergen:2002, Abstract = {The life-long addition of new neurons has been documented in many regions of the vertebrate and invertebrate brain, including the hippocampus of mammals (Altman and Das, 1965; Eriksson et al., 1998; Jacobs et al., 2000), song control nuclei of birds (Alvarez-Buylla et al., 1990), and olfactory pathway of rodents (Lois and Alvarez-Buylla, 1994), insects (Cayre et al., 1996) and crustaceans (Harzsch and Dawirs, 1996; Sandeman et al., 1998; Harzsch et al., 1999; Schmidt, 2001). The possibility of persistent neurogenesis in the neocortex of primates is also being widely discussed (Gould et al., 1999; Kornack and Rakic, 2001). In these systems, an effort is underway to understand the regulatory mechanisms that control the timing and rate of neurogenesis. Hormonal cycles (Rasika et al., 1994; Harrison et al., 2001), serotonin (Gould, 1999; Brezun and Daszuta, 2000; Beltz et al., 2001), physical activity (Van Praag et al., 1999) and living conditions (Kemperman and Gage, 1999; Sandeman and Sandeman, 2000) influence the rate of neuronal proliferation and survival in a variety of organisms, suggesting that mechanisms controlling life-long neurogenesis are conserved across a range of vertebrate and invertebrate species. The present article extends these findings by demonstrating circadian control of neurogenesis. Data show a diurnal rhythm of neurogenesis among the olfactory projection neurons in the crustacean brain, with peak proliferation during the hours surrounding dusk, the most active period for lobsters. These data raise the possibility that light-controlled rhythms are a primary regulator of neuronal proliferation, and that previously-demonstrated hormonal and activity-driven influences over neurogenesis may be secondary events in a complex circadian control pathway. 0022-3034 Journal Article}, Author = {Goergen, E. M. and Bagay, L. A. and Rehm, K. and Benton, J. L. and Beltz, B. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurobiol}, Keywords = {F abstr;10 Development;Brain/*physiology;Neuronal Plasticity;Cell Division;Cell Count;Circadian Rhythm/*physiology;Support, U.S. Gov't, Non-P.H.S.;Nephropidae/*physiology;Neurons/physiology;Support, Non-U.S. Gov't;Animals;Feeding Behavior/physiology;Morphogenesis/physiology}, Number = {1}, Organization = {Department of Biological Sciences, Wellesley College, Wellesley, Massacusetts 02481, USA.}, Pages = {90-5}, Pubmed = {12360586}, Title = {Circadian control of neurogenesis}, Uuid = {6DFCC4CE-CCDC-11D9-8C77-000D9346EC2A}, Volume = {53}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12360586}} @article{Goerner:2001, Abstract = {Previous studies have shown that the choice of envelope protein (pseudotype) can have a significant effect on the efficiency of retroviral gene transfer into hematopoietic stem cells. This study used a competitive repopulation assay in the dog model to evaluate oncoretroviral vectors carrying the envelope protein of the endogenous feline virus, RD114. CD34-enriched marrow cells were divided into equal aliquots and transduced with vectors produced by the RD114-pseudotype packaging cells FLYRD (LgGLSN and LNX) or by the gibbon ape leukemia virus (GALV)-pseudotype packaging cells PG13 (LNY). A total of 5 dogs were studied. One dog died because of infection before sustained engraftment could be achieved, and monitoring was discontinued after 9 months in another animal that had very low overall gene-marking levels. The 3 remaining animals are alive with follow-ups at 11, 22, and 23 months. Analyses of gene marking frequencies in peripheral blood and marrow by polymerase chain reaction revealed no significant differences between the RD114 and GALV-pseudotype vectors. The LgGLSN vector also contained the enhanced green fluorescent protein (GFP), enabling us to monitor proviral expression by flow cytometry. Up to 10\%of peripheral blood cells expressed GFP shortly after transplantation and approximately 6\%after the longest follow-up of 23 months. Flow cytometric analysis of hematopoietic subpopulations showed that most of the GFP-expressing cells were granulocytes, although GFP-positive lymphocytes and monocytes were also detected. In summary, these results show that RD114-pseudotype oncoretroviral vectors are able to transduce hematopoietic long-term repopulating cells and, thus, may be useful for human stem cell gene therapy.}, Author = {Goerner, M. and Horn, P. A. and Peterson, L. and Kurre, P. and Storb, R. and Rasko, J. E. and Kiem, H. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Transduction, Genetic;Follow-Up Studies;Animals;Blood Cells;Bone Marrow Transplantation;Comparative Study;Endogenous Retroviruses;Antigens, CD34;Retroviridae Proteins;11 Glia;Green Fluorescent Proteins;Genetic Vectors;Bone Marrow Cells;Hematopoiesis;Leukemia Virus, Gibbon Ape;Survival Rate;Cell Lineage;Amino Acid Transport System ASC;Research Support, U.S. Gov't, P.H.S.;Receptors, Virus;Luminescent Proteins;Graft Survival;Cats;Dogs;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {21452787}, Month = {10}, Nlm_Id = {7603509}, Number = {7}, Organization = {Divisions of Clinical Research and Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.}, Pages = {2065-70}, Pubmed = {11567991}, Title = {Sustained multilineage gene persistence and expression in dogs transplanted with CD34(+) marrow cells transduced by RD114-pseudotype oncoretrovirus vectors}, Uuid = {6A2C0978-748A-4762-99BA-FA62503D8398}, Volume = {98}, Year = {2001}} @article{Goffinet:2006, Abstract = {ABSTRACT: For a neurobiologist, the core of human nature is the human cerebral cortex, especially the prefrontal areas, and the question what makes us human? translates into studies of the development and evolution of the human cerebral cortex, a clear oversimplification. In this comment, after pointing out this oversimplification, I would like to show that it is impossible to understand our cerebral cortex if we focus too narrowly on it. Like other organs, our cortex evolved from that in stem amniotes, and it still bears marks of that ancestry. More comparative studies of brain development are clearly needed if we want to understand our brain in its historical context. Similarly, comparative genomics is a superb tool to help us understand evolution, but again, studies should not be limited to mammals or to comparisons between human and chimpanzee, and more resources should be invested in investigation of many vertebrate phyla. Finally, the most widely used rodent models for studies of cortical development are of obvious interest but they cannot be considered models of a stem cortex from which the human type evolved. It remains of paramount importance to study cortical development directly in other species, particularly in primate models, and, whenever ethically justifiable, in human.}, Author = {Goffinet,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1747-5333}, Journal = {J Biomed Discov Collab}, Keywords = {24 Pubmed search results 2008;19 Neocortical evolution}, Month = {11}, Nlm_Id = {101258054}, Number = {1}, Pages = {13}, Pii = {1747-5333-1-13}, Pubmed = {17132178}, Title = {What makes us human ? A biased view from the perspective of comparative embryology and mouse genetics}, Uuid = {CDFA26DE-8F9B-4A54-B091-B825252EE91E}, Volume = {1}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1747-5333-1-13}} @article{Goffinet:1999, Abstract = {The expression of reelin mRNA and protein was studied during embryonic brain development in the lacertilian lizards L. viridis and L. galloti, by using radioactive in situ hybridization and immunohistochemistry. At all stages studied, high reelin expression was consistently found in the olfactory bulb, in the lateral cortex, and in neurons of the marginal zone and subplate of medial and dorsal cortical sectors. In the dorsal ventricular ridge (DVR), reelin expression was confined to deeply located, large cells which were more abundant in the caudal than the rostral part of the DVR. In the diencephalon, the ventral lateral geniculate complex and the perirotundal were strongly positive, whereas other nuclei were mostly negative. High reelin signal was associated with some layers in the tectum, with the torus semicircularis, cerebellar granule cell layers, and the ventral horn of the spinal cord. A more moderate signal was detected in the septal nuclei, striatum, retina, habenular nuclei, preoptic and periventricular hypothalamic components, and in reticular nuclei of the mid- and hindbrain. The medial and dorsal cortical plate and Purkinje cells were reelin-negative but expressed disabled-1 (Dab1) mRNA. When they are compared with reelin expression during mammalian brain development, our data reveal an evolutionarily conserved canvas of reelin expression, as well as significant differences, particularly in developing cortical fields. The developing lizard cortex differs from that of turtles, birds, crocodiles, and mammals in that it displays heavy reelin expression not only in neurons of the marginal zone that might be homologous to mammalian Cajal-Retzius cells, but also in subplate neurons. This difference in the pattern of reelin expression suggests that the elaborate radial organization of the lacertilian cortical plate, somewhat reminiscent of its mammalian counterpart, results from evolutionary convergence. Our data lend support to the hypothesis that the reelin signaling pathway played a significant role during cortical evolution. 0021-9967 Journal Article}, Author = {Goffinet, A. M. and Bar, I. and Bernier, B. and Trujillo, C. and Raynaud, A. and Meyer, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Comp Neurol}, Keywords = {In Situ Hybridization;Brain Chemistry/physiology;Immunohistochemistry;Brain Stem/*embryology;Prosencephalon/*embryology;Cell Division;Cell Adhesion Molecules, Neuronal/*genetics;RNA, Messenger/analysis;Gene Expression;Extracellular Matrix Proteins/*genetics;N;Support, Non-U.S. Gov't;Animals;Cerebellum/*embryology;Lizards/*embryology;19 Neocortical evolution}, Number = {4}, Organization = {Neurobiology Unit, University of Namur School of Medicine, B-5000 Namur, Belgium. Andre.Goffinet\@fundp.ac.be}, Pages = {533-50}, Pubmed = {10531544}, Title = {Reelin expression during embryonic brain development in lacertilian lizards}, Uuid = {FDB17E9F-A3B3-4AF6-978A-B2B99453C7CB}, Volume = {414}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10531544}} @article{Gofflot:2007, Abstract = {Nuclear receptors (NRs) compose a large family of transcription factors that operate at the interface between genes and environment, acting as sensors and effectors that translate endocrine and metabolic cues into well-defined gene expression programs. We report here on a systematic quantitative and anatomical expression atlas of the 49 NR genes in 104 regions of the adult mouse brain, organized in the interactive MousePat database. MousePat defines NR expression patterns to cellular resolution, a requirement for functional genomic strategies to understand the function of a highly heterogeneous and complex organ such as the brain. Using MousePat data, NR expression patterns can be clustered into anatomical and regulatory networks that delineate the role of NRs in brain functions, like the control of feeding and learning/memory. Mining the MousePat resource will improve the understanding of NR function in the brain and elucidate hierarchical networks that control behavior and whole body homeostasis.}, Author = {Gofflot, Fran\c{c}oise and Chartoire, Nathalie and Vasseur, Laurent and Heikkinen, Sami and Dembele, Doulaye and Le Merrer, Julie and Auwerx, Johan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {In Situ Hybridization;24 Pubmed search results 2008;10 Development;Databases, Nucleic Acid;Hypothalamus;Hippocampus;Receptors, Cytoplasmic and Nuclear;Reverse Transcriptase Polymerase Chain Reaction;Mice, Inbred C57BL;Gene Expression Profiling;Learning;Animals;Male;Mice;Feeding Behavior;Transcription Factors}, Month = {10}, Nlm_Id = {0413066}, Number = {2}, Organization = {Institut Clinique de la Souris, 67404 Illkirch, France.}, Pages = {405-18}, Pii = {S0092-8674(07)01196-8}, Pubmed = {17956739}, Title = {Systematic gene expression mapping clusters nuclear receptors according to their function in the brain}, Uuid = {DA8601FE-031D-4023-9A95-E407D997D428}, Volume = {131}, Year = {2007}, url = {papers/Gofflot_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2007.09.012}} @article{Gohlke:2004, Abstract = {We are quantitatively evaluating the acquisition of neocortical neurons through key stages of development including neurogenesis, migration, and synaptogenesis. Here we expand upon a previous computational model describing neocortical neurogenesis in the rat and mouse [Dev. Neurosci. 24 (2002) 467], to include the period of synaptogenesis (P0-P14) when programmed cell death (PCD) is known to play a major role in shaping the neocortex. We also quantitatively evaluate differing hypotheses on the role of cell death during neurogenesis. This new model construct allows prediction of acquisition of adult neuronal number in the rat and mouse neocortex from the beginning of neurogenesis through synaptogenesis. The mathematical model output is validated by independently derived stereologically determined neuron number estimates in the adult rat and mouse. Simulations suggest cell death during synaptogenesis reduces the neocortical neuronal population by 20-30\%, while cell death of progenitor cells and newly formed neurons during neurogenesis may reduce output by as much as 24\%. However, higher death rates during neurogenesis as suggested by some research would deplete the progenitor population, not allowing for the vast expansion that is the hallmark of the mammalian neocortex. Furthermore, our simulations suggest the clearance time of dying neurons labeled by TUNEL or pyknosis is relatively short, between 1 and 4 h, corroborating experimental research. This novel mathematical model for adult neocortical neuronal acquisition allows for in silico analysis of normal and perturbed states of neocortical development as well as interspecies and evolutionary analyses of neocortical development. 0165-3806 Journal Article}, Author = {Gohlke, J. M. and Griffith, W. C. and Faustman, E. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {F, EE pdf;08 Aberrant cell cycle}, Number = {1-2}, Organization = {Center for Child Environmental Health Risks Research, Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA 98105-6099, USA.}, Pages = {43-54}, Title = {The role of cell death during neocortical neurogenesis and synaptogenesis: implications from a computational model for the rat and mouse}, Uuid = {EA1D2407-C723-44FF-9845-50AA6D4BEB49}, Volume = {151}, Year = {2004}, url = {papers/Gohlke_BrainResDevBrainRes2004.pdf}} @article{Goings:2004, Abstract = {The subventricular zone (SVZ) generates the largest number of migratory cells in the adult brain. SVZ neuroblasts migrate to the olfactory bulbs (OB) in the adult, whereas during development, SVZ cells migrate into many adjacent nuclei. Previously, we showed that cerebral cortex injury in the adult causes molecular and cellular changes which may recapitulate the developmental migratory directions. Consistent with this, growth factors, as well as models of illness or injury can cause adult SVZ cells to migrate into non-olfactory bulb nuclei. Here, we tested the hypothesis that cerebral cortex injury in the adult mouse induces changes in migration, by labeling adult SVZ cells with a retroviral vector and examining the distribution of cells 4 days and 3 weeks later. Four days after cortical lesions, disproportionately fewer retrovirally-labeled cells had migrated to the olfactory bulb in lesioned mice than in controls. Conversely, the number of cells found in non-olfactory bulb regions (primarily the area of the lesion and the corpus callosum) was increased in lesioned mice. The morphology of these emigrated cells suggested that they were differentiating into glial cells. Three weeks after cortical injury, the majority of retrovirally-labeled cells in both groups of mice had migrated into the granule and periglomerular layers of the olfactory bulb. At 3 weeks, we still observed retrovirally-labeled glial cells in the corpus callosum and in the area of the injury in lesioned mice. These results suggest that cortical lesions cause a transient change in migration patterns of SVZ progeny, which is characterized by decreases in migration to the olfactory bulb but increased migration towards the injury. Our studies also suggest that cortical lesions induce the production of new glial cells which survive for at least 3 weeks after injury. The data support the concept that in the adult, SVZ cells can generate progeny that migrate towards injured areas and thus potentially be harnessed for neural repair. 0006-8993 Journal Article}, Author = {Goings, G. E. and Sahni, V. and Szele, F. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Brain Res}, Keywords = {06 Adult neurogenesis injury induced;D pdf}, Number = {2}, Organization = {CMIER Neurobiology Program, Department of Pediatrics, 2300 Children's Plaza, No. 209, Children's Memorial Hospital, Feinberg School of Medicine, Northwestern University, 60614-3394, Chicago, IL, USA}, Pages = {213-26}, Title = {Migration patterns of subventricular zone cells in adult mice change after cerebral cortex injury}, Uuid = {187A79A0-DCD9-41B5-91D9-41F2E3E64208}, Volume = {996}, Year = {2004}, url = {papers/Goings_BrainRes2004.pdf}} @article{Goldberg:2003, Abstract = {GABAergic interneurones are essential in cortical processing, yet the functional properties of their dendrites are still poorly understood. In this first study, we combined two-photon calcium imaging with whole-cell recording and anatomical reconstructions to examine the calcium dynamics during action potential (AP) backpropagation in three types of V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). Somatically generated APs actively backpropagated into the dendritic tree and evoked instantaneous calcium accumulations. Although voltage-gated calcium channels were expressed throughout the dendritic arbor, calcium signals during backpropagation of both single APs and AP trains were restricted to proximal dendrites. This spatial control of AP backpropagation was mediated by Ia-type potassium currents and could be mitigated by by previous synaptic activity. Further, we observed supralinear summation of calcium signals in synaptically activated dendritic compartments. Together, these findings indicate that in interneurons, dendritic AP propagation is synaptically regulated. We propose that interneurones have a perisomatic and a distal dendritic functional compartment, with different integrative functions.}, Author = {Goldberg, Jesse H. and Tamas, Gabor and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Animals;Electric Conductivity;Synapses;research support, u.s. gov't, p.h.s. ;Neocortex;Mice, Inbred C57BL;Calcium;21 Calcium imaging;Dendrites;research support, non-u.s. gov't ;Action Potentials;Potassium Channels;21 Neurophysiology;Calcium Channels;Mice;Interneurons;24 Pubmed search results 2008;Visual Cortex;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {0266262}, Number = {Pt 1}, Organization = {Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, NY 10027, USA. jhg24\@columbia.edu}, Pages = {49-65}, Pii = {2003.042580}, Pubmed = {12844506}, Title = {Ca2+ imaging of mouse neocortical interneurone dendrites: Ia-type K+ channels control action potential backpropagation}, Uuid = {AFFDB08C-D8C1-4FA9-9552-09D5E86B1322}, Volume = {551}, Year = {2003}, url = {papers/Goldberg_JPhysiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2003.042580}} @article{Goldberg:2003a, Abstract = {In this second study, we have combined two-photon calcium imaging with whole-cell recording and anatomic reconstructions to directly characterize synaptically evoked calcium signals in three types of mouse V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD). We observed that subthreshold synaptic activation evoked calcium signals locally restricted to individual dendritic compartments. These signals were mediated by NMDA receptors (NMDARs) in AD and IS cells, whereas in FS cells, calcium-permeable AMPA receptors (CP-AMPARs) provided an additional and kinetically distinct influx. Furthermore, even a single, subthreshold synaptic activation evoked a larger dendritic calcium influx than backpropagating action potentials. Our results demonstrate that NMDARs dominate subthreshold calcium dynamics in interneurones and reveal the functional contribution of CP-AMPARs to a specific subclass of cortical interneurone. These data highlight different strategies in dendritic signal processing by distinct classes of interneurones.}, Author = {Goldberg, Jesse H. and Yuste, Rafael and Tamas, Gabor}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Electric Stimulation;Calcium Signaling;Synapses;Animals;research support, u.s. gov't, p.h.s. ;Neocortex;in vitro ;Kinetics;Receptors, AMPA;Mice, Inbred C57BL;Calcium;Reaction Time;21 Calcium imaging;Dendrites;research support, non-u.s. gov't ;Action Potentials;21 Neurophysiology;Differential Threshold;Receptors, Neurotransmitter;Mice;Interneurons;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {0266262}, Number = {Pt 1}, Organization = {Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, NY 10027, USA. jhg24\@columbia.edu}, Pages = {67-78}, Pii = {2003.042598}, Pubmed = {12844507}, Title = {Ca2+ imaging of mouse neocortical interneurone dendrites: contribution of Ca2+-permeable AMPA and NMDA receptors to subthreshold Ca2+dynamics}, Uuid = {D96F0408-4A59-4669-81ED-316C568FEBEC}, Volume = {551}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2003.042598}} @article{Goldberg:2005, Abstract = {Dendrites of pyramidal neurons are complex, electrically active structures that can produce local and global Ca(2+) compartments. Recent studies indicate that dendrites of cortical GABAergic interneurons are also highly specialized, and that different subtypes vary in their morphology, in their intrinsic and synaptic conductances and in the Ca(2+) signals they generate. Because interneurons play a major role in oscillations, understanding their dendrites could offer key insights into rhythmogenesis. Different interneuron subtypes have different synaptic integration properties and generate differentially timed inhibition at distinct sites of the pyramidal neuraxis. In addition, interneuron dendrites generate diverse Ca(2+) signals that reflect this circuit function and probably also implement subclass-specific plasticity and homeostasis.}, Author = {Goldberg, Jesse H. and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Synapses;research support, u.s. gov't, p.h.s. ;Dendrites;Neural Networks (Computer);21 Neurophysiology;Receptors, AMPA;21 Calcium imaging;Calcium;Interneurons;Calcium Signaling;Animals;Cerebral Cortex;review;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7808616}, Number = {3}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA. jhg24\@columbia.edu}, Pages = {158-67}, Pii = {S0166-2236(05)00025-1}, Pubmed = {15749170}, Title = {Space matters: local and global dendritic Ca2+ compartmentalization in cortical interneurons}, Uuid = {E982DB44-840B-435C-956C-64DA1E5FAFB5}, Volume = {28}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2005.01.005}} @article{Goldin:2003, Abstract = {The roles of protein kinase C and the MAP-kinase extracellular receptor kinase in structural changes associated with long-term potentiation of network activity were examined in cultured hippocampal neurons. A brief exposure to a conditioning medium that favours activation of the N-methyl-d-aspartate receptor caused a rapid and specific increase in staining of neurons for the phosphorylated form of extracellular receptor kinase as well as of cyclic AMP response element binding protein. Exposure of the cultures to the conditioning medium was followed by a protein synthesis-dependent formation of novel dendritic spines. An extracellular receptor kinase antagonist PD98059 blocked the phosphorylated form of extracellular receptor kinase response and the formation of novel spines. A selective protein kinase C agonist, phorbol 12-myristate 13-acetate, caused activation of extracellular receptor kinase and formation of novel spines. The protein kinase C antagonist GF109203x blocked the phosphorylated form of extracellular receptor kinase response and the subsequent spine formation by phorbol 12-myristate 13-acetate. Both the conditioning medium and phorbol 12-myristate 13-acetate caused a delayed increase in mean amplitude of miniature excitatory postsynaptic currents recorded in the hippocampal neurons. These results indicate that activation of extracellular receptor kinase mediates the effect of a conditioning protocol on the formation of dendritic spines. The formation of novel spines was associated with long-term increase in network activity and functional synaptic connectivity among the cultured neurons.}, Author = {Goldin, Miri and Segal, Menahem}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;research support, non-u.s. gov't ;24 Pubmed search results 2008;Green Fluorescent Proteins;Immunohistochemistry;Luminescent Proteins;Animals;Cells, Cultured;Protein Kinase C;comparative study ;Hippocampus;Imaging, Three-Dimensional;Transcription Factors;Transfection;Quinoxalines;Drug Interactions;Analysis of Variance;Activating Transcription Factor 1;Dendrites;Neuronal Plasticity;Culture Media, Conditioned;DNA-Binding Proteins;Enzyme Inhibitors;Time Factors;Rats;Patch-Clamp Techniques;Animals, Newborn;Cell Size;21 Neurophysiology;Valine;Mice;Neurons;Mitogen-Activated Protein Kinases;in vitro ;Excitatory Postsynaptic Potentials}, Month = {6}, Nlm_Id = {8918110}, Number = {12}, Organization = {Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel.}, Pages = {2529-39}, Pii = {2694}, Pubmed = {12823460}, Title = {Protein kinase C and ERK involvement in dendritic spine plasticity in cultured rodent hippocampal neurons}, Uuid = {F098906F-C7DA-4DD5-B4CD-3985913812E2}, Volume = {17}, Year = {2003}, url = {papers/Goldin_EurJNeurosci2003.pdf}} @article{Goldin:2001, Abstract = {Despite widespread interest in dendritic spines, little is known about the mechanisms responsible for spine formation, retraction, or stabilization. We have now found that a brief exposure of cultured hippocampal neurons to a conditioning medium that favors activation of the NMDA receptor produces long-term modification of their spontaneous network activity. The conditioning protocol enhances correlated activity of neurons in the culture, in a process requiring an increase in [Ca(2+)](i) and is associated with both formation of novel dendritic spines and pruning of others. The novel spines are likely to be touched by a presynaptic terminal, labeled with FM4-64 dye, whereas the absence of such terminals increases the likelihood of spine pruning. These results indicate that long-term functional changes are correlated with morphological modifications of dendritic spines of neurons in a network.}, Author = {Goldin, M. and Segal, M. and Avignone, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Fluorescent Dyes;Animals;Synapses;Cells, Cultured;Rats;Neuronal Plasticity;Egtazic Acid;research support, u.s. gov't, non-p.h.s. ;Patch-Clamp Techniques;2-Amino-5-phosphonovalerate;Culture Media, Conditioned;Hippocampus;Dendrites;research support, non-u.s. gov't ;Nerve Net;21 Neurophysiology;Neurons;Quaternary Ammonium Compounds;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Pyridinium Compounds;Excitatory Postsynaptic Potentials}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Department of Neurobiology, The Weizmann Institute, Rehovot 76100, Israel.}, Pages = {186-93}, Pii = {21/1/186}, Pubmed = {11150335}, Title = {Functional plasticity triggers formation and pruning of dendritic spines in cultured hippocampal networks}, Uuid = {26E141CD-F80F-48EC-9B10-F9BB81963D9A}, Volume = {21}, Year = {2001}, url = {papers/Goldin_JNeurosci2001.pdf}} @article{Goldmakher:2000, Abstract = {The periglomerular (PG) cells of the accessory olfactory bulb (AOB) are GABAergic interneurons which receive input from the vomeronasal sensory neurons and form dendrodendritic synapses with each other and with mitral cells. Their electrophysiological properties have not been investigated. We have developed a novel method of isolating PG cells from the AOB, and used the whole-cell patch and gramicidin-perforated patch clamp techniques to measure their basic electrophysiological characteristics and their response to GABA. PG cells were found to be excitable neurons with voltage-gated Na(+) and K(+) currents, though it was very difficult to get PG cells to fire an action potential. The voltage-gated Na(+) currents of PG cells activate at more positive potentials than those of typical CNS neurons. PG cells respond to GABA with currents in which GABA(A) receptors play a significant role. A subset ( approximately 40\%) of PG cells respond to GABA with currents which have unusually high reversal potentials, indicating that GABA may be excitatory to these neurons. This phenomenon cannot be explained entirely by elevation of intracellular chloride concentrations, and is dependent on the presence of extracellular sodium.}, Author = {Goldmakher, G. V. and Moss, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Brain Res}, Keywords = {13 Olfactory bulb anatomy;Neurons/*cytology/drug effects/*physiology;Cell Separation;I;Rats;Potassium Channels/antagonists &inhibitors/physiology;Patch-Clamp Techniques;Female;Animal;Sodium Channels/antagonists &inhibitors/physiology;GABA/*pharmacology;Tetrodotoxin/pharmacology;Support, U.S. Gov't, P.H.S.;Sodium/*physiology;Olfactory Bulb/*cytology/physiology;Tetraethylammonium/pharmacology;Receptors, GABA-A/physiology;Action Potentials/drug effects;Gramicidin}, Number = {1}, Organization = {Department of Physiology, UT Southwestern Medical Center, 75235, Dallas, TX, USA. goldmakh2utsw.swmed.edu}, Pages = {7-15.}, Title = {A subset of periglomerular neurons in the rat accessory olfactory bulb may be excited by GABA through a Na(+)-dependent mechanism}, Uuid = {65FBEB72-7F75-4C52-91AC-B33006F3B128}, Volume = {871}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10882777}} @article{Goldman:1997, Author = {Goldman, S. A. and Nedergaard, M. and Crystal, R. G. and Fraser, R. A. and Goodman, R. and Harrison-Restelli, C. and Jiang, J. and Keyoung, H. M. and Leventhal, C. and Pincus, D. W. and Shahar, A. and Wang, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Ann N Y Acad Sci}, Keywords = {02 Adult neurogenesis migration;Cell Division/physiology;Adult;03 Adult neurogenesis progenitor source;Human;Mammals;Animal;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Age Factors;Brain/*cytology;BB abstr;Stem Cells/*cytology}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.}, Pages = {30-55.}, Title = {Neural precursors and neuronal production in the adult mammalian forebrain}, Uuid = {861ED51D-D6FE-468D-93CC-28256DE22A03}, Volume = {835}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9616760}} @article{Goldman:1996, Abstract = {The songbird forebrain continues to generate neurons in adulthood, from precursor cells located in the ependymal /subependymal zone (SZ) over the mediocaudal neostriatum. Precursor mitosis is followed by migration of neuronal daughter cells into the underlying forebrain, along radial fibers derived from the SZ. To define the ontogeny of both the new neurons and their radial guide cells, we employed retroviral insertion of the lacZ gene into neostriatal SZ precursor cells derived from postnatal and adult songbirds. We found that single SZ cells generate both neurons and substrate glia in vitro, and in an analogous fashion, both neurons and radial cells in vivo. This suggests that newly generated neurons and radial cells of the adult avian brain derive from a common pluripotential progenitor.}, Author = {Goldman, S. A. and Zukhar, A. and Barami, K. and Mikawa, T. and Niedzwiecki, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurobiol}, Keywords = {Cells, Cultured;Neurons/*cytology/physiology;Brain/*cytology;Animal;Cell Movement;02 Adult neurogenesis migration;Birds/*physiology;Stem Cells/cytology;Ependyma/*cytology;Retroviridae;Genetic Vectors;BB abstr;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;Gene Transfer Techniques;Animals, Newborn/*physiology;Lac Operon;Support, U.S. Gov't, P.H.S.;Canaries/*physiology;Cell Division}, Number = {4}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York 10021, USA.}, Pages = {505-20.}, Title = {Ependymal/subependymal zone cells of postnatal and adult songbird brain generate both neurons and nonneuronal siblings in vitro and in vivo}, Uuid = {1D86CC3C-F01A-4066-8A6C-C85E78F7BD34}, Volume = {30}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8844514}} @article{Goldman:1997a, Abstract = {The adult mammalian brain continues to harbor ependymal/subependymal zone (SZ) precursor cells, which can give rise to neurons in vitro. In adult rats, explants of the rostral 6-7 mm of the SZ give rise to neurons in vitro, and over this entire expanse, neuronal survival is supported specifically by brain-derived neurotrophic factor (BDNF). We asked whether either the (a) spatial distribution, (b) abundance, or (c) BDNF responsiveness of the neuronal precursor population was affected by age. Explants of three rostrocaudally defined regions were taken from both young and old rats (3 and 20 months old, respectively), and cultured in 2\%fetal bovine serum-containing media with or without added BDNF (20 ng/ml). The extent of neuronal production by these explants varied only minimally with their level of derivation, such that substantial outgrowth was observed at each level tested. Neuronal outgrowth was marginally higher and more rapid in achieving its maximal extent in the 3-month-old rats compared with their aged counterparts, but neuronal outgrowth was robust at each age tested. The duration of survival of SZ-derived neurons did not differ between the young and old rats. At both ages, BDNF supported the survival of these new adult neurons. The extent of BDNF's influence was independent of both the age of the donor rat and the rostrocaudal level at which the parent SZ explant was taken. Thus, the neuronal precursors of the rat brain persist into senescence; the size of the precursor pool attenuates minimally with age, and its spatial extent remains constant. The neurons generated from these precursors can respond to BDNF throughout life. 0022-3034 Journal Article}, Author = {Goldman, S. A. and Kirschenbaum, B. and Harrison-Restelli, C. and Thaler, H. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurobiol}, Keywords = {Neurons/*cytology/drug effects/physiology;Animals;Cell Survival/drug effects;Rats;Rats, Sprague-Dawley;Mammals;Brain-Derived Neurotrophic Factor/*pharmacology;Aging/*physiology;C abstr;Male;Brain/*cytology/growth &development;Cattle;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Culture Media;Recombinant Proteins/pharmacology;Organ Culture}, Number = {6}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.}, Pages = {554-66}, Pubmed = {9183737}, Title = {Neuronal precursors of the adult rat subependymal zone persist into senescence, with no decline in spatial extent or response to BDNF}, Uuid = {06BB6542-5673-4260-B89F-409BA40FA723}, Volume = {32}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9183737}} @article{Goldman:1998, Abstract = {Neuronal precursor cells persist in the adult vertebrate forebrain, residing primarily in the ventricular/subventricular zone (SZ). In vivo, SZ precursors yield progeny which may die or give rise to glia. Yet they may also generate neurons, which are recruited to restricted regions such as the avian telencephalon and mammalian olfactory bulb. The survival of neurons arising from adult progenitors is dictated by both the availability of a permissive pathway for migration and the environment into which migration occurs. In the songbird higher vocal center (HVC), both humoral and contact-mediated signals modulate the migration and survival of new neurons, through an orchestrated set of hormonally regulated paracrine interactions. New neurons of the songbird brain depart the SZ to enter the brain parenchyma by migrating upon radial guide fibers, which emanate from cell bodies in the ventricular epithelium. The radial guide cells coderive with new neurons from a common progenitor, which is widespread throughout the songbird SZ. Neural precursors are also widely distributed in the adult mammalian SZ, although it is unclear whether avian and mammalian progenitor cells are homologous: Whereas neuronal recruitment persists throughout much of the songbird forebrain, in mammals it is limited to the olfactory bulb. In humans, the adult SZ appears to largely cease neurogenesis in vivo, although it, too, can produce neurons in vitro. In both rats and humans, the differentiation and survival of neurons arising from the postnatal SZ may be regulated by access to postmitotic trophic factors. Indeed, serial application of fibroblast growth factor- 2 (FGF-2) and brain-derived neurotrophic factor (BDNF) has allowed the generation and maintenance of neurons from the adult human SZ. This suggests the feasibility of inducing neurogenesis in the human brain, both in situ and through implanted progenitors. In this regard, using cell-specific neural promoters coupled to fluorescent reporters, defined progenitor phenotypes may now be isolated by fluorescence- activated cell sorting. Together, these findings give hope that structural brain repair through induced neurogenesis and neurogenic implants will soon be a clinical reality.}, Author = {Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Neurobiol}, Keywords = {Brain/cytology/*growth &development;01 Adult neurogenesis general;Human;A-8c;Rodentia/growth &development;Aging/physiology;Animal;Support, U.S. Gov't, P.H.S.;Neurons/physiology;Stem Cells/physiology;Support, Non-U.S. Gov't;Canaries/growth &development;Cell Movement/physiology}, Number = {2}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.}, Pages = {267-86.}, Title = {Adult neurogenesis: from canaries to the clinic}, Uuid = {AFE0F4C6-64C4-4CB5-9550-D089FDEC1DB6}, Volume = {36}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9712309}} @article{Goldman:1995, Abstract = {We have been examining the developmental fates and migrational patterns of the immature cells in the subventricular zone (SVZ) of the mammalian forebrain by labeling postnatal rat SVZ cells by stereotactic injection of replication-deficient murine retroviruses bearing reporter genes. SVZ cells migrate into adjacent white matter, cortex, and striatum, and differentiate into astrocytes and oligodendrocytes. In white matter, they largely differentiate into oligodendrocytes, whereas in gray matter, they differentiate into both oligodendrocytes and astrocytes. In vitro, SVZ cells are multipotential, able to generate both types of glia, as well as neurons. We infer that developmental fates are in part controlled by important environmental cues that the cells encounter during their migration. Using Smart Source Parsing}, Author = {Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {J Neurooncol}, Keywords = {Prosencephalon/*cytology;02 Adult neurogenesis migration;Cell Division/physiology;Neurons/immunology;Rats;Stereotaxic Techniques;Neuroglia/immunology;Animal;Support, U.S. Gov't, P.H.S.;Stem Cells/physiology;B abstr;Cell Movement/*physiology;Cell Aging/*physiology}, Number = {1}, Organization = {Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.}, Pages = {61-4}, Title = {Lineage, migration, and fate determination of postnatal subventricular zone cells in the mammalian CNS}, Uuid = {63B8C239-2DA7-4357-AE72-27F057F246A2}, Volume = {24}, Year = {1995}, url = {papers/Goldman_JNeurooncol1995.pdf}} @article{Goldman:1983, Abstract = {The vocal control nucleus designated HVc (hyperstriatum ventrale, pars caudalis) of adult female canaries expands in response to systemic testosterone administration, which also induces the females to sing in a male-like manner. We became interested in the possibility of neurogenesis as a potential basis for this phenomenon. Intact adult female canaries were injected with [3H]thymidine over a 2-day period. Some birds were given testosterone implants at various times before thymidine. The birds were sacrificed 5 wk after hormone implantation, and their brains were processed for autoradiography. In parallel control experiments, some birds were given implants of cholesterol instead of testosterone. All birds showed considerable numbers of labeled neurons, glia, endothelia, and ventricular zone cells in and around HVc. Ultrastructural analysis confirmed the identity of these labeled neurons. Cholesterol- and testosterone-treated birds had similar neuronal labeling indices, which ranged from 1.8\%to 4.0\%in HVc. Thus, neurogenesis occurred in these adults independently of exogenous hormone treatment. Conversely, both glial and endothelial proliferation rates were markedly stimulated by exogenous testosterone treatment. We determined the origin of the thymidine-incorporating neurons by sacrificing two thymidine-treated females soon after their thymidine injections, precluding any significant migration of newly labeled cells. Analysis of these brains revealed no cells of neuronal morphology present in HVc but a very heavily labeled ventricular zone overlying HVc. We conclude that neuronal precursors exist in the HVc ventricular zone that incorporate tritiated thymidine during the S phase preceding their mitosis; after division these cells migrate into, and to some extent beyond, HVc. This ventricular zone neurogenesis seems to be a normally occurring phenomenon in intact adult female canaries.}, Author = {Goldman, S. A. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Division/drug effects;02 Adult neurogenesis migration;B;Neurons/cytology;Female;Thymidine/metabolism;Animal;Testosterone/pharmacology;Brain/physiology;Canaries/*physiology;Neuroglia/cytology;Endothelium/cytology;Support, U.S. Gov't, P.H.S.;Vocalization, Animal/drug effects/*physiology}, Number = {8}, Pages = {2390-4.}, Title = {Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain}, Uuid = {1C2C47F9-0048-4145-94BA-24181CA18484}, Volume = {80}, Year = {1983}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=6572982}} @article{Goldman:1998a, Abstract = {Structural brain repair has become a possibility with the identification and characterization of persistent neuronal progenitor cells in both the neonatal and adult brain. However, despite recent advances in the identification, propagation and expansion of these cells, they will not be useful therapeutically until methods are available for directing or delivering them to sites of need. As a result, the natural history and induction of neuronal migration into adult brain tissue has assumed new importance in clinical neurobiology. In this review we consider the cellular and molecular bases of neuronal migration into the postnatal forebrain. In particular, we discuss two natural paradigms of postnatal neuronal recruitment: radial-cell- directed neuronal migration to the songbird neostriatum, and neurophilic migration to the rodent olfactory bulb. In each, we will focus on the dynamic interactions between the migrants, their cellular guides and the local environment, and the effect of those interactions on migrational success.}, Author = {Goldman, S. A. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Trends Neurosci}, Keywords = {Prosencephalon/*cytology;Vertebrates/growth &development/*physiology;02 Adult neurogenesis migration;Neurons/*physiology;Aging/physiology;Animals, Newborn/*physiology;Animal;Support, U.S. Gov't, P.H.S.;B abstr;Support, Non-U.S. Gov't;Cell Movement/physiology}, Number = {3}, Organization = {Dept of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.}, Pages = {107-14.}, Title = {Strategies utilized by migrating neurons of the postnatal vertebrate forebrain}, Uuid = {1C7BDB93-B13D-4020-A1D0-CEAAAF76327B}, Volume = {21}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9530917%20http://www.biomednet.com/library/fulltext/pii.S0166223697011910}} @article{Goldman:2003, Abstract = {Recent studies have substantially expanded our conception of the roles for glia in function and maintenance of the adult nervous system. Of these reports, several have re-examined the lineage relationships among neural stem cells, their early radial glial derivatives and their mitotically competent neurogenic daughters. These studies have highlighted the role of radial cells in development, and of their glial progeny postnatally, as both progenitors and regulators of neuronal production and phenotype. In the adult mammalian brain, radial cell populations are scant, but their glial derivatives participate in a gliovascular network that organizes not only the structural and functional architecture of the brain but also its generative niches for resident progenitors - glial as well as neuronal. As in other organs, these progenitors can reside as transit-amplifying pools, by which lineage-biased progenitors expand to replenish discrete mature phenotypes. This review will consider the types of transit-amplifying progenitor cells persistent in the adult mammalian CNS, and the extent to which these derive from glial phenotypes. It will also discuss the interactions of progenitor cells with their brethren that could specify their phenotype and fate, while defining the permissive niches for cell genesis in the adult CNS.}, Author = {Goldman, Steve}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Cell Lineage;Ependyma;Glial Fibrillary Acidic Protein;Neuroglia;Cell Differentiation;03 Adult neurogenesis progenitor source;Mammals;Epithelial Cells;Stem Cells;11 Glia;Adaptation, Physiological;review, tutorial;Animals;Cell Movement;Cerebral Cortex;review;Neurons}, Medline = {22949172}, Month = {11}, Nlm_Id = {7808616}, Number = {11}, Organization = {Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. sgoldm\@med.cornell.edu}, Pages = {590-6}, Pii = {S0166223603002947}, Pubmed = {14585598}, Title = {Glia as neural progenitor cells}, Uuid = {B0A8CADF-7213-4D5C-832D-2B29D25A6B1E}, Volume = {26}, Year = {2003}} @article{Goldman-Rakic:1995, Abstract = {0896-6273 Journal Article Review Review, Tutorial}, Author = {Goldman-Rakic, P. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Neuron}, Keywords = {18 Classic Neuroanatomy Physiology;Neurons/*physiology;Brain/*physiology;Memory/*physiology;Human;Models, Neurological;Models, Psychological;M;Brain Mapping;Animals;Prefrontal Cortex/physiology}, Number = {3}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510.}, Pages = {477-85}, Pubmed = {7695894}, Title = {Cellular basis of working memory}, Uuid = {A67686F8-0364-47D9-BC0C-CFA6FF3552CC}, Volume = {14}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7695894}} @article{Gong:2002, Abstract = {p21(WAF1/CIP1) is a universal cyclin-dependent kinase inhibitor. To investigate the role of p21(WAF1/CIP1) in proliferation of human liver cancer cells, we examined the expression of p53, p21(WAF1/CIP1), cdk2 and cdk4 expression in two human liver cancer cell lines (HepG2 and PLC/PRF/5 cells). The effects of p21(WAF1/CIP1) on [(3)H]thymidine incorporation and cdks were also examined in these cells. HepG2 cells expressed all these proteins with lower level of cdk4. PLC/PRF/5 cells expressed the other proteins except p21(WAF1/CIP1). Transfection of p21(WAF1/CIP1) gene inhibited [(3)H]thymidine incorporation of both cells with different extent. Although the transfection of p21(WAF1/CIP1) did not affect cdk2 and cdk4 expression, it did reduce cdk2 kinase activity by 20\%. These results suggest that: (a) p21(WAF1/CIP1) involved in DNA synthesis of human liver cancer cells; (b) p21(WAF1/CIP1) could be a target gene for the treatment of human hepatocellular carcinoma. 0007-0920 Journal Article}, Author = {Gong, Y. and Deng, S. and Zhang, M. and Wang, G. and Minuk, G. Y. and Burczynski, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Br J Cancer}, Keywords = {Human;EE both;Cyclin-Dependent Kinases/metabolism;Carcinoma, Hepatocellular/*metabolism;Liver Neoplasms/*metabolism;Transfection;Adenosine Triphosphate/metabolism;Protein-Serine-Threonine Kinases/metabolism;08 Aberrant cell cycle;DNA/biosynthesis;Thymidine/*metabolism;Blotting, Northern;Cyclins/*physiology;Blotting, Western;Tumor Cells, Cultured;*CDC2-CDC28 Kinases;Support, Non-U.S. Gov't;Protein p53/metabolism;DNA, Neoplasm/*metabolism}, Number = {4}, Organization = {Department of Internal Medicine, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. ygong\@ms.umanitoba.ca}, Pages = {625-9}, Title = {A cyclin-dependent kinase inhibitor (p21(WAF1/CIP1)) affects thymidine incorporation in human liver cancer cells}, Uuid = {4CC88BDC-2BE4-4C20-AE32-957E4BA19249}, Volume = {86}, Year = {2002}, url = {papers/Gong_BrJCancer2002.pdf}} @article{Gongidi:2004, Abstract = {Differential adhesion between migrating neurons and transient radial glial fibers enables the deployment of neurons into appropriate layers in the developing cerebral cortex. The identity of radial glial signals that regulate the termination of migration remains unclear. Here, we identified a radial glial surface antigen, SPARC (secreted protein acidic and rich in cysteine)-like 1, distributed predominantly in radial glial fibers passing through the upper strata of the cortical plate (CP) where neurons end their migration. Neuronal migration and adhesion assays indicate that SPARC-like 1 functions to terminate neuronal migration by reducing the adhesivity of neurons at the top of the CP. Cortical neurons fail to achieve appropriate positions in the absence of SPARC-like 1 function in vivo. Together, these data suggest that antiadhesive signaling via SPARC-like 1 on radial glial cell surfaces may enable neurons to recognize the end of migration in the developing cerebral cortex. 0896-6273 Journal Article}, Author = {Gongidi, V. and Ring, C. and Moody, M. and Brekken, R. and Sage, E. H. and Rakic, P. and Anton, E. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Neuron}, Keywords = {F abstr;10 Development}, Number = {1}, Organization = {UNC Neuroscience Center, Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, 27599, Chapel Hill, NC, USA}, Pages = {57-69}, Pubmed = {14715135}, Title = {SPARC-like 1 Regulates the Terminal Phase of Radial Glia-Guided Migration in the Cerebral Cortex}, Uuid = {6C97D6B0-E94C-48A2-B8F2-7E3E62A48027}, Volume = {41}, Year = {2004}, url = {papers/Gongidi_Neuron2004.pdf}} @article{Gonzalez:2002, Abstract = {Rats received lesions of the posterior cingulate cortex or both the anterior and posterior cingulate cortex (total cingulate), or sham procedures, on postnatal Day 10. As adults, animals were trained in the Morris water task. Both the cingulate lesion groups showed substantial functional recovery relative to our previous studies of adult operates or animals with perinatal cingulate lesions. A Golgi analyis of layer III pyramidal cells in parietal cortex showed an increase in dendritic length in the lesion animals relative to sham controls, which is similar to previous findings for rats with anterior cingulate but not motor or parietal lesions. In addition, there was a partial regeneration of the anterior tissue in the total cingulates, which in some cases extended into the posterior region. This is consistent with earlier findings that anterior cingulate lesions around Day 10 stimulate neurogenesis. It appears that there is something special about the reparative processes and subsequent functional recovery that follow midline neocortical lesions. 21845910 0012-1630 Journal Article}, Author = {Gonzalez, C. L. and Gibb, R. and Kolb, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0012-1630}, Journal = {Dev Psychobiol}, Keywords = {06 Adult neurogenesis injury induced;Dendrites/*physiology/ultrasonography;Nerve Regeneration;24 Pubmed search results 2008;Gyrus Cinguli;Male;Escape Reaction;Cerebral Cortex;Animals;Recall/physiology;Mental Recall;Rats, Long-Evans;Brain Mapping;Dendrites;Nerve Regeneration/*physiology;D;Neuronal Plasticity;Maze Learning;Pyramidal Cells/physiology/ultrasonography;Escape Reaction/physiology;Gyrus Cinguli/anatomy &histology/*physiology;Animal;Reference Values;Pyramidal Cells;Maze Learning/physiology;Rats;Female;Cerebral Cortex/anatomy &histology/physiology;Support, Non-U.S. Gov't;Research Support, Non-U.S. Gov't;Neuronal Plasticity/*physiology}, Medline = {21845910}, Month = {3}, Nlm_Id = {0164074}, Number = {2}, Organization = {Department of Psychology and Neuroscience, University of Lethbridge, Lethbridge, Canada T1K 3M4.}, Pages = {138-46}, Pii = {10.1002/dev.10024}, Pubmed = {11857328}, Title = {Functional recovery and dendritic hypertrophy after posterior and complete cingulate lesions on postnatal day 10}, Uuid = {8FE5D68B-9D2C-47D3-A97A-8457BD1E5F4C}, Volume = {40}, Year = {2002}, url = {papers/Gonzalez_DevPsychobiol2002.pdf}} @article{Gonzalez:2003, Abstract = {Neonatal posterior cingulate cortex lesions spare the spatial deficits that characterize adult lesions. The present experiments examined the possibility that the anterior cingulate cortex mediates the spared spatial behavior. Rats were given bilateral lesions of the posterior cingulate cortex or anterior plus posterior cingulate cortex on postnatal days 4 (P4), 10 (P10), or in adulthood (P120). All groups were tested for spatial learning on the Morris place task in adulthood. Adult animals were impaired on place learning relative to controls whereas place learning was spared in all the neonatal groups and sparing was complete in the group receiving day 10 lesions. The results are discussed in relation to neural mechanisms, including fiber rerouting, synaptic changes and generation of new neurons, that may mediate spared spatial following neonatal posterior cingulate cortex lesions. Also discussed is evidence indicating that the neonatal brain, especially the day 10, has a special ability to compensate for injury.}, Author = {Gonzalez, C. L. R. and Whishaw, I. Q. and Kolb, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Gyrus Cinguli;Research Support, Non-U.S. Gov't;Rats, Long-Evans;Female;Comparative Study;Rats;Spatial Behavior;Animals, Newborn;Learning;Reaction Time;Male;Animals;Cerebral Cortex;24 Pubmed search results 2008}, Medline = {22980524}, Nlm_Id = {7605074}, Number = {2}, Organization = {Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge T1K 3M4, AB, Canada.}, Pages = {563-71}, Pii = {S0306452203002951}, Pubmed = {14614920}, Title = {Complete sparing of spatial learning following posterior and posterior plus anterior cingulate cortex lesions at 10 days of age in the rat}, Uuid = {5F7C14C0-FD2B-4994-8703-C7B4A32854CE}, Volume = {122}, Year = {2003}} @article{Gonzalez:1997, Abstract = {The reeler mutation in mice produces an especially well characterized disorder, with systematically abnormal migration of cerebral cortical neurons. The reeler gene encodes a large protein, termed Reelin, that in the cortex is synthesized and secreted exclusively in the Cajal-Retzius neurons of the cortical marginal zone (D'Arcangelo et al., 1995). In reeler mutant mice, loss of Reelin protein is associated with a systematic loss of the normal, "inside-out" sequence of neurogenesis in the cortex: neurons are formed in the normal sequence but become localized in the cortex in a somewhat inverted, although relatively disorganized "outside-in" pattern. Here we show that the scrambler mutant mouse exhibits a loss of lamination in the cortex and hippocampus that is indistinguishable from that seen in the reeler mouse. We use BrdU birthdating studies to show that scrambler cortex shows a somewhat inverted "outside-in" sequence of birthdates for cortical neurons that is similar to that previously described in reeler cortex. Finally, we perform staining with the CR-50 monoclonal antibody (Ogawa et al., 1995), which recognizes the Reelin protein (D'Arcangelo et al., 1997). We show that Reelin immunoreactivity is present in the scrambler cortex in a normal pattern, suggesting that Reelin is synthesized and released normally. Our data suggest that scrambler is a mutation in the same gene pathway as the reeler gene (Relnrl) and is most likely downstream of Relnrl.}, Author = {Gonz{\'a}lez, J. L. and Russo, C. J. and Goldowitz, D. and Sweet, H. O. and Davisson, M. T. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:46 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {10 Development;Animals;Gene Expression Regulation, Developmental;comparative study;Phenotype;Cell Movement;Hippocampus;Serine Endopeptidases;Cell Adhesion Molecules, Neuronal;research support, non-u.s. gov't;Mice, Neurologic Mutants;Cerebellar Cortex;Extracellular Matrix Proteins;Cell Lineage;Morphogenesis;research support, u.s. gov't, p.h.s.;Cerebral Cortex;10 genetics malformation;Neurons;Genetic Heterogeneity;Mice;24 Pubmed search results 2008;Biological Markers;Gestational Age;research support, u.s. gov't, non-p.h.s.;Nerve Tissue Proteins}, Month = {12}, Nlm_Id = {8102140}, Number = {23}, Organization = {Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {9204-11}, Pubmed = {9364067}, Title = {Birthdate and cell marker analysis of scrambler: a novel mutation affecting cortical development with a reeler-like phenotype}, Uuid = {EE57A0FC-9E1E-4098-AD8D-59B261531242}, Volume = {17}, Year = {1997}, url = {papers/González_JNeurosci1997.pdf}} @article{Gonzalez-Scarano:1999, Abstract = {Microglia are the principal immune cells in the central nervous system (CNS) and have a critical role in host defense against invading microorganisms and neoplastic cells. However, as with immune cells in other organs, microglia may play a dual role, amplifying the effects of inflammation and mediating cellular degeneration as well as protecting the CNS. In entities like human immunodeficiency virus (HIV) infection of the nervous system, microglia are also critical to viral persistence. In this review we discuss the role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease.}, Author = {Gonz{\'a}lez-Scarano, F. and Baltuch, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0147-006X}, Journal = {Annu Rev Neurosci}, Keywords = {HIV Infections;Multiple Sclerosis;Nerve Degeneration;Inflammation;Research Support, U.S. Gov't, P.H.S.;Alzheimer Disease;Microglia;review, tutorial;11 Glia;Animals;Humans;Central Nervous System Diseases;review}, Medline = {99218863}, Nlm_Id = {7804039}, Organization = {Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104-6146, USA. Scarano\@mail.med.upenn.edu}, Pages = {219-40}, Pubmed = {10202538}, Title = {Microglia as mediators of inflammatory and degenerative diseases}, Uuid = {EDECA05C-A0DE-4DE5-ADF8-3B20E06AAE0D}, Volume = {22}, Year = {1999}, url = {papers/González-Scarano_AnnuRevNeurosci1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.22.1.219}} @article{Goodenough:1996, Abstract = {Cells in tissues share ions, second messengers, and small metabolites through clusters of intercellular channels called gap junctions. This type of intercellular communication permits coordinated cellular activity. Intercellular channels are formed from two oligomeric integral membrane protein assemblies, called connexons, which span two adjacent cells' plasma membranes and join in a narrow, extracellular "gap." Connexons are formed from connexins, a highly related multigene family consisting of at least 13 members. Since the cloning of the first connexin in 1986, considerable progress has been made in our understanding of the complex molecular switches that control the formation and permeability of the intercellular channels. Analysis of the mechanisms of channel assembly has revealed the selectivity of inter-connexin interactions and uncovered novel characteristics of the channel permeability and gating behavior. Structure-function studies provide a molecular understanding of the significance of connexin diversity and demonstrate the unique regulation of connexins by tyrosine kinases and oncogenes.}, Author = {Goodenough, D. A. and Goliger, J. A. and Paul, D. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0066-4154}, Journal = {Annu Rev Biochem}, Keywords = {24 Pubmed search results 2008;Structure-Activity Relationship;research support, non-u.s. gov't;21 Neurophysiology;Cell Communication;Intracellular Membranes;research support, u.s. gov't, p.h.s.;Animals;Connexins;Lipid Metabolism;review;Phosphorylation}, Nlm_Id = {2985150R}, Organization = {Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {475-502}, Pubmed = {8811187}, Title = {Connexins, connexons, and intercellular communication}, Uuid = {3F9E9319-7C99-4910-A60F-5DCDE609DBE2}, Volume = {65}, Year = {1996}, url = {papers/Goodenough_AnnuRevBiochem1996.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.bi.65.070196.002355}} @article{Goodier:2008, Abstract = {Retrotransposons, mainly LINEs, SINEs, and endogenous retroviruses, make up roughly 40\%of the mammalian genome and have played an important role in genome evolution. Their prevalence in genomes reflects a delicate balance between their further expansion and the restraint imposed by the host. In any human genome only a small number of LINE1s (L1s) are active, moving their own and SINE sequences into new genomic locations and occasionally causing disease. Recent insights and new technologies promise answers to fundamental questions about the biology of transposable elements.}, Author = {Goodier, John L. and Kazazian, Haig H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0413066}, Number = {1}, Organization = {Department of Genetics, University of Pennsylvania School of Medicine, 415 Curie Boulevard, Philadelphia, PA 19104, USA. jgoodier\@mail.med.upenn.edu}, Pages = {23-35}, Pii = {S0092-8674(08)01179-3}, Pubmed = {18854152}, Title = {Retrotransposons revisited: the restraint and rehabilitation of parasites}, Uuid = {6DAD9E9C-47EE-4388-977F-7EA386EB0339}, Volume = {135}, Year = {2008}, url = {papers/Goodier_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.09.022}} @article{Gopal:2007, Abstract = {The mammalian neocortex comprises two major neuronal subtypes; interneurons derived from the ganglionic eminence (GE) and projection neurons from the cortical ventricular zone (VZ). These separate origins necessitate distinct pathways of migration. Using mouse genetics and embryonic forebrain slice culture assays, we sought to identify substrates and/or guidance molecules for nonradial cell migration (NRCM). Mice carrying a mutation in Pax6 (Sey(-/-)), a paired domain transcription factor, are reported to have increased numbers of cortical inhibitory interneurons, suggesting that Pax6 could induce inhibitors of interneuron development or alternatively play a repressive role in guiding NRCM and/or specifying interneurons. Unexpectedly, we found a cell nonautonomous reduction in the distance Sey(-/-) neurons migrated, reflecting a disorganized migration, with frequent changes in direction. In contrast, no difference in the number of nonradially migrating GE cells was observed in Sey(-/-) mice. Our data indicate that the increased numbers of interneurons observed in Sey(-/-) do not result from an increased rate or number of nonradially migrating cells; instead, loss of Pax6 results in the ectopic specification of interneurons in the cortical VZ. Further, our data indicate that the known axonal disorganization in Sey(-/-) mice contributes to the observed reduced distance of NRCM.}, Author = {Gopal, and Golden,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {9110718}, Organization = {Neuroscience Program, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.}, Pii = {bhm114}, Pubmed = {17634386}, Title = {Pax6 / Mice Have a Cell Nonautonomous Defect in Nonradial Interneuron Migration}, Uuid = {3CF564F6-1FFC-4E7D-846C-71E1094DAF44}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhm114}} @article{Gordon:1996, Author = {Gordon, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0012-1622}, Journal = {Dev Med Child Neurol}, Keywords = {Epilepsy;21 Epilepsy;Electroencephalography;21 Neurophysiology;Humans;Cell Movement;24 Pubmed search results 2008;Neurons;review}, Medline = {97070261}, Month = {11}, Nlm_Id = {0006761}, Number = {11}, Pages = {1053-7}, Pubmed = {8913187}, Title = {Epilepsy and disorders of neuronal migration. I: Introduction}, Uuid = {639E4205-71F1-4D71-AD80-D74834231B92}, Volume = {38}, Year = {1996}} @article{Gorji:2003, Abstract = {In vitro and in vivo brain slice techniques were used to examine phencyclidine (PCP) effects on the lateral propagation of epileptiform field potentials (EFP) across adjacent areas of rat frontal neocortex. Epileptiform activity was induced by perfusing slices with Mg 2+-free artificial cerebrospinal fluid. Simultaneous field potential recordings of EFP were obtained from four microelectrodes placed 2-3 mm apart across coronal slices in the third layer. PCP, applied focally between recording sites, blocked rapid propagation across treated areas and resulted in the emergence of spatially separate, independent pacemakers. The characteristics of paroxysmal depolarization shifts did not change significantly by the blockade of lateral propagation of EFP. The same asynchronized pattern of EFP conduction was observed after local application of the N-methyl-D-aspartate (NMDA)-receptor antagonist DL-2-amino-5-phosphono-valeric acid. Local administration of haloperidol as well as NMDA before PCP application reversibly prevented appearance of multiple pacemakers. Focal application of dopamine produced an abnormal pattern of lateral conduction of EFP in 50 \%of tested slices. Pacemaker failure as an indicator of functional impairment of cortical integration is the proposed mechanism for developing of schizophrenia-like psychosis associated with epilepsy. Abbreviations. APV: DL-2-amino-5-phosphono-valeric acid EEG:electroencephalogram EFP:epileptiform field potentials NMDA:N-methyl-D-aspartate PCP:phencyclidine SLPE:Schizophrenialike psychosis associated with epilepsy}, Author = {Gorji, A. and Scheller, D. and Speckmann, E-J J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0176-3679}, Journal = {Pharmacopsychiatry}, Keywords = {Epilepsy;Microelectrodes;24 Pubmed search results 2008;Magnesium;21 Epilepsy;21 Neurophysiology;Bicuculline;Rats;Neural Conduction;In Vitro;Electrophysiology;Phencyclidine;Receptors, N-Methyl-D-Aspartate;Convulsants;Cerebral Cortex;Animals;Excitatory Amino Acid Antagonists}, Medline = {22690038}, Month = {5}, Nlm_Id = {8402938}, Number = {3}, Organization = {Institut f{\"u}r Physiologie, Universit{\"a}t M{\"u}nster, 48149 M{\"u}nster, Germany. gorjial\@uni-muenster.de}, Pages = {113-20}, Pubmed = {12806569}, Title = {The lateral spread of epileptiform discharges in rat neocortical slices: effect of focal phencyclidine application}, Uuid = {8824DDDD-1492-40A1-9A9D-0F485C79BD99}, Volume = {36}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1055/s-2003-39986}} @article{Gosse:2008, Abstract = {The retinotectal projection has long been studied experimentally and theoretically, as a model for the formation of topographic brain maps. Neighbouring retinal ganglion cells (RGCs) project their axons to neighbouring positions in the optic tectum, thus re-establishing a continuous neural representation of visual space. Mapping along this axis requires chemorepellent signalling from tectal cells, expressing ephrin-A ligands, to retinal growth cones, expressing EphA receptors. High concentrations of ephrin A, increasing from anterior to posterior, prevent temporal axons from invading the posterior tectum. However, the force that drives nasal axons to extend past the anterior tectum and terminate in posterior regions remains to be identified. We tested whether axon-axon interactions, such as competition, are required for posterior tectum innervation. By transplanting blastomeres from a wild-type (WT) zebrafish into a lakritz (lak) mutant, which lacks all RGCs, we created chimaeras with eyes that contained single RGCs. These solitary RGCs often extended axons into the tectum, where they branched to form a terminal arbor. Here we show that the distal tips of these arbors were positioned at retinotopically appropriate positions, ruling out an essential role for competition in innervation of the ephrin-A-rich posterior tectum. However, solitary arbors were larger and more complex than under normal, crowded conditions, owing to a lack of pruning of proximal branches during refinement of the retinotectal projection. We conclude that dense innervation is not required for targeting of retinal axons within the zebrafish tectum but serves to restrict arbor size and shape.}, Author = {Gosse, Nathan J. and Nevin, Linda M. and Baier, Herwig}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {DNA-Binding Proteins;Zebrafish;research support, non-u.s. gov't;Models, Neurological;Zebrafish Proteins;research support, n.i.h., extramural;Retinal Ganglion Cells;Animals;Superior Colliculi;24 Pubmed search results 2008;Axons}, Month = {4}, Nlm_Id = {0410462}, Number = {7189}, Organization = {Program in Developmental Biology, University of California, San Francisco, Department of Physiology, 1550 Fourth Street, San Francisco, California 94158-2324, USA.}, Pages = {892-5}, Pii = {nature06816}, Pubmed = {18368050}, Title = {Retinotopic order in the absence of axon competition}, Uuid = {93E8B78F-EABD-469C-8FEE-B36963424799}, Volume = {452}, Year = {2008}, url = {papers/Gosse_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06816}} @article{Gotts:2005, Abstract = {Neural cell migration and differentiation may participate in neural repair after adult brain injury; however, the survival and differentiation of newly born cells after different brain lesions are poorly understood. We have examined the migration and fate of bromodeoxyuridine (BrdU)-labeled cells after a highly reproducible focal ischemic lesion restricted to the frontoparietal cortex in adult rats. Thermocoagulation of pial blood vessels induces a circumscribed degeneration of all cortical layers while sparing the corpus callosum and striatum and increases cell proliferation in the subventricular zone (SVZ) and rostral migratory stream (RMS) within 7 days. We now show that, although the rostral migration of the newly born SVZ cells and their differentiation into neurons in the olfactory bulb were not affected by the lesion, numerous cells expressing the neuroblast marker doublecortin migrated laterally in the striatum and corpus callosum 5 days postinjury. In addition to the SVZ, BrdU-labeled cells were seen in the striatum, in the corpus callosum, and around the lesion. One month later, BrdU-labeled cells in the corpus callosum expressed transferrin and the pi isoform of glutathione-S-transferase (GST-pi), markers of oligodendrocytes. Other BrdU(+) cells expressed a marker of astrocytes, but none expressed neuronal markers, suggesting that new neurons do not form or survive under these conditions. Numerous BrdU-labeled cells were still observed in the SVZ and RMS. The data show that focal cortical ischemia does not lead to the long-term survival of new neurons in the striatum or cortex but induces long-term alterations in the SVZ and the production of new oligodendrocytes that may contribute to neural repair. (c) 2005 Wiley-Liss, Inc.}, Author = {Gotts, Jeffrey E. and Chesselet, Marie-Franc\c{c}oise F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {06 Adult neurogenesis injury induced}, Month = {4}, Nlm_Id = {7600111}, Number = {2}, Organization = {Departments of Neurology and Neurobiology, Geffen School of Medicine at UCLA, Los Angeles, California.}, Pages = {160-71}, Pubmed = {15751027}, Title = {Migration and fate of newly born cells after focal cortical ischemia in adult rats}, Uuid = {2797906E-D6C4-4165-8084-960A6857795C}, Volume = {80}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20434}} @article{Gotz:1998, Abstract = {Radial glia cells perform a dual function in the developing nervous system as precursor cells and guides for migrating neurons. We show here that during forebrain neurogenesis, the transcription factor Pax6 is specifically localized in radial glia cells of the cortex but not of the basal telencephalon. In Pax6-deficient mice, cortical radial glia cells were altered in their morphology, number, tenascin-C (TN-C) expression, and cell cycle. We show that some of these alterations are cell-autonomous, whereas others were rescued by coculturing with wild-type cortical cells. Our results suggest that Pax6 plays an essential role in the differentiation of cortical radial glia. Thus, despite their widespread distribution, radial glia cells are regionally specified in the developing CNS. 0896-6273 Journal Article}, Author = {Gotz, M. and Stoykova, A. and Gruss, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Neuron}, Keywords = {10 Development;Growth Substances/*physiology;DNA-Binding Proteins/genetics/*physiology;Cell Differentiation/genetics;Cells, Cultured;Animals;Cerebral Cortex/*cytology/growth &development/pathology;Neuroglia/*cytology/metabolism/pathology;Stem Cells/metabolism;Mice, Mutant Strains;Mutation;Mice, Inbred C57BL;Embryo;F both;Support, Non-U.S. Gov't;Mice, Knockout;Mice;*Homeodomain Proteins}, Number = {5}, Organization = {Department of Molecular Cell Biology, Max-Planck Institute of Biophysical Chemistry, Gottingen, Federal Republic of Germany.}, Pages = {1031-44}, Title = {Pax6 controls radial glia differentiation in the cerebral cortex}, Uuid = {7B1C5503-424A-4A4B-90A1-6B0B8FAD5569}, Volume = {21}, Year = {1998}, url = {papers/Gotz_Neuron1998}} @article{Gould:1994, Abstract = {The dentate gyrus of the rat forms in three developmental phases, each of which is characterized by neuronal birth, migration and death. Recent evidence indicates that adrenal steroids regulate neuronal birth, death, and possibly migration throughout the life of the animal. However, the observation that very few neuroblasts in the developing or adult dentate gyrus express adrenal steroid receptors suggests that the effects of adrenal steroid manipulations on neurogenesis are indirect. Additional evidence indicates that NMDA receptor activation regulates neuronal birth and death in this brain region presenting the possibility that adrenal steroids influence these processes through direct actions on excitatory afferents. Future studies will address this possibility.}, Author = {Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {Ann N Y Acad Sci}, Keywords = {Aging;Neurons/*cytology/*physiology;Amino Acids/*physiology;Cell Division;Cell Survival;Adrenal Cortex Hormones/*physiology;Hippocampus/embryology/growth &development;Fetal Development;Animal;04 Adult neurogenesis factors;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;C- abst only}, Organization = {Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.}, Pages = {73-92; discussion 92-3.}, Title = {The effects of adrenal steroids and excitatory input on neuronal birth and survival}, Uuid = {7317F0BA-AE69-43AC-989F-92E12679505C}, Volume = {743}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7802420}} @article{Gould:1991, Abstract = {The rat dentate gyrus undergoes a period of naturally occurring cell death during the first postnatal week. In the adult rat, removal of circulating adrenal steroids by adrenalectomy is followed by massive death in the granule cell layer, thus raising the possibility that developmental cell death results from low levels of these hormones. Interestingly, the first two postnatal weeks of life in the rat, termed the stress hyporesponsive period, are characterized by very low levels of adrenal steroids. In order to determine whether low levels of adrenal steroids enable developmental cell death to occur in the dentate gyrus, we examined the density of pyknotic and healthy cells in the dentate gyrus of rat pups which received one of the following treatments: (1) injections of the endogenous rat glucocorticoid corticosterone during the first postnatal week, or (2) adrenalectomy at the time when glucocorticoid levels normally rise. Quantitative analysis of the density of pyknotic cells in the granule cell layers revealed significant decreases with corticosterone treatment by the end of the first postnatal week. In these same brains, treatment with corticosterone resulted in a substantial increase in the density of pyknotic cells in the hilus. Adrenalectomy resulted in a significant increase in the density of pyknotic cells in the granule cell layer as well as in the hilus. Despite the dramatic alterations in the density of pyknotic cells with both increases and decreases in glucocorticoid levels, the density of healthy cells remained the same. These observations suggest that glucocorticoids regulate several processes, possibly including neurogenesis and migration, in addition to cell death.}, Author = {Gould, E. and Woolley, C. S. and McEwen, B. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:53 -0400}, Journal = {J Comp Neurol}, Keywords = {C abst only;Rats;Corticosterone/*pharmacology;Adrenal Cortex Hormones/*physiology;Animal;Neurons/*drug effects/physiology;04 Adult neurogenesis factors;Hippocampus/cytology/drug effects/*growth &development;Animals, Newborn;Support, Non-U.S. Gov't;Cell Survival/drug effects;Adrenalectomy;Rats, Inbred Strains;Support, U.S. Gov't, P.H.S.}, Number = {3}, Organization = {Laboratory of Neuroendocrinology, Rockefeller University, New York, New York 10021.}, Pages = {479-85.}, Title = {Adrenal steroids regulate postnatal development of the rat dentate gyrus: I. Effects of glucocorticoids on cell death}, Uuid = {6746B068-A216-4610-A627-18447C845B24}, Volume = {313}, Year = {1991}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1770171}} @article{Gould:2002, Author = {Gould, E. and Gross, C. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;Brain/*cytology/growth &development/metabolism;Cell Division/physiology;Bromodeoxyuridine/pharmacokinetics;Cell Survival/physiology;Human;Antigens, Differentiation/biosynthesis;A both;Cell Count;Cell Differentiation/physiology;Animal;Neuroglia/cytology;Neurons/*cytology/metabolism;Staining and Labeling/methods;Dentate Gyrus/cytology}, Number = {3}, Organization = {Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA. goulde\@princeton.edu}, Pages = {619-23.}, Title = {Neurogenesis in adult mammals: some progress and problems}, Uuid = {9C09BCDE-D20C-11D9-B244-000D9346EC2A}, Volume = {22}, Year = {2002}, url = {papers/Gould_JNeurosci2002.pdf}} @article{Gould:1999, Abstract = {Thousands of hippocampal neurons are born in adulthood, suggesting that new cells could be important for hippocampal function. To determine whether hippocampus-dependent learning affects adult-generated neurons, we examined the fate of new cells labeled with the thymidine analog bromodeoxyuridine following specific behavioral tasks. Here we report that the number of adult-generated neurons doubles in the rat dentate gyrus in response to training on associative learning tasks that require the hippocampus. In contrast, training on associative learning tasks that do not require the hippocampus did not alter the number of new cells. These findings indicate that adult-generated hippocampal neurons are specifically affected by, and potentially involved in, associative memory formation.}, Author = {Gould, E. and Beylin, A. and Tanapat, P. and Reeves, A. and Shors, T. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Nat Neurosci}, Keywords = {Physical Conditioning, Animal/physiology;Rats;Association Learning/physiology;Animal;Rats, Sprague-Dawley;Male;01 Adult neurogenesis general;A-8b;Cell Division/physiology;Dentate Gyrus/*cytology/*physiology;Blinking/physiology;Maze Learning/physiology;Neurons/cytology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Learning/*physiology;Cues;Conditioning, Classical/physiology}, Number = {3}, Organization = {Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA.}, Pages = {260-5.}, Title = {Learning enhances adult neurogenesis in the hippocampal formation}, Uuid = {A888F3BE-8662-4ED1-90CE-A7608C12B9CD}, Volume = {2}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10195219}} @article{Gould:2007, Abstract = {It is now widely accepted that neurogenesis occurs in two regions of the adult mammalian brain - the hippocampus and the olfactory bulb. There is evidence for adult neurogenesis in several additional areas, including the neocortex, striatum, amygdala and substantia nigra, but this has been difficult to replicate consistently other than in the damaged brain. The discrepancies may be due to variations in the sensitivity of the methods used to detect new neurons.}, Author = {Gould, Elizabeth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {100962781}, Number = {6}, Organization = {Elizabeth Gould is at the Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA. goulde\@princeton.edu.}, Pages = {481-8}, Pii = {nrn2147}, Pubmed = {17514200}, Title = {How widespread is adult neurogenesis in mammals?}, Uuid = {73BDD42A-0BDA-4D14-AFA9-CFA577D0E620}, Volume = {8}, Year = {2007}, url = {papers/Gould_NatRevNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2147}} @article{Gould:1999a, Abstract = {The production of new hippocampal neurons in adulthood has been well documented in rodents. Recent studies have extended these findings to other mammalian species, such as tree shrews and marmoset monkeys. However, hippocampal neurogenesis has not been demonstrated in adult Old World primates. To investigate this possibility, we injected 11 adult Old World monkeys of different ages (5-23 years) with the thymidine analog bromodeoxyuridine and examined the fate of the labeled cells at different survival times by using neuronal and glial markers. In the young-adult and middle-aged monkeys, we found a substantial number of cells that incorporated bromodeoxyuridine and exhibited morphological and biochemical characteristics of immature and mature neurons. New cells located in the dentate gyrus expressed a marker of immature granule neurons, Turned On After Division 64 kDa protein, as well as markers of mature granule neurons including neuron specific enolase, neuronal nuclei, and the calcium-binding protein calbindin. Fewer new cells expressed the astroglial marker glial fibrillary acidic protein. Evidence of neurogenesis was observed in the oldest monkeys (23 years) as well, but it appeared to be less robust. These results indicate that the adult brains of Old World monkeys produce new hippocampal neurons. Adult macaque monkeys may provide a useful primate model for studying the functional significance of adult neurogenesis.}, Author = {Gould, E. and Reeves, A. J. and Fallah, M. and Tanapat, P. and Gross, C. G. and Fuchs, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Microscopy, Confocal;Aging;Cell Division/physiology;Female;Neurons/*cytology/physiology;A abstr;Hippocampus/*cytology/physiology;Cell Count;Cercopithecidae;Cell Differentiation/physiology;Animal;Support, U.S. Gov't, P.H.S.;Male}, Number = {9}, Organization = {Department of Psychology, Princeton University, Princeton NJ 08544, USA. goulde\@princeton.edu}, Pages = {5263-7.}, Title = {Hippocampal neurogenesis in adult Old World primates}, Uuid = {9FB6E308-67A7-11DA-A4B6-000D9346EC2A}, Volume = {96}, Year = {1999}, url = {papers/Gould_ProcNatlAcadSciUSA1999.pdf}} @article{Gould:2001, Abstract = {Previously we reported that new neurons are added to the hippocampus and neocortex of adult macaque monkeys. Here we compare the production and survival of adult-generated neurons and glia in the dentate gyrus, prefrontal cortex, and inferior temporal cortex. Twelve adult macaques were injected with the thymidine analogue BrdUrd, and the phenotypes of labeled cells were examined after 2 h, 24 h, 2 wk, 5 wk, 9 wk, and 12 wk by using the following immunocytochemical markers: for immature and mature neurons, class III beta-tubulin (TuJ1); for mature neurons, neuronal nuclei; for astrocytes, glial fibrillary acidic protein; and for oligodendrocytes, 2',3'-cyclic nucleotide 3'phosphodiesterase. We found that the dentate gyrus had many more BrdUrd-labeled cells than either neocortical area. Furthermore, a greater percentage of BrdUrd- labeled cells expressed a neuronal marker in the dentate gyrus than in either neocortical area. The number of new cells in all three areas declined by 9 wk after BrdUrd labeling, suggesting that some of the new cells have a transient existence. BrdUrd-labeled cells also were found in the subventricular zone and in the white matter between the lateral ventricle and neocortex; some of the latter cells were double-labeled for BrdUrd and TuJ1. Adult neocortical neurogenesis is not restricted to primates. Five adult rats were injected with BrdUrd, and after a 3- wk survival time, there were cells double-labeled for BrdUrd and either TuJ1 or neuronal nuclei in the anterior neocortex as well as the dentate gyrus. Using Smart Source Parsing Aug}, Author = {Gould, E. and Vail, N. and Wagers, M. and Gross, C. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {A;01 Adult neurogenesis general}, Organization = {Department of Psychology, Princeton University, Princeton, NJ 08544.}, Pages = {28}, Title = {Adult-generated hippocampal and neocortical neurons in macaques have a transient existence}, Uuid = {66B2AFC8-D247-11D9-A0E9-000D9346EC2A}, Volume = {28}, Year = {2001}, url = {papers/Gould_ProcNatlAcadSciUSA2001.pdf}} @article{Gould:1999b, Abstract = {In primates, prefrontal, inferior temporal, and posterior parietal cortex are important for cognitive function. It is shown that in adult macaques, new neurons are added to these three neocortical association areas, but not to a primary sensory area (striate cortex). The new neurons appeared to originate in the subventricular zone and to migrate through the white matter to the neocortex, where they extended axons. These new neurons, which are continually added in adulthood, may play a role in the functions of association neocortex.}, Author = {Gould, E. and Reeves, A. J. and Graziano, M. S. and Gross, C. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Journal = {Science}, Keywords = {Cell Survival;Cell Differentiation;Temporal Lobe/*cytology/physiology;Aging;Neurons/*cytology/physiology;Microscopy, Confocal;Axons/ultrastructure;Prefrontal Cortex/*cytology/physiology;Female;Cell Movement;Animal;Parietal Lobe/*cytology/physiology;Macaca fascicularis;Male;Support, Non-U.S. Gov't;Lateral Ventricles/cytology;Support, U.S. Gov't, P.H.S.;Visual Cortex/cytology/physiology;A-9 both;Neocortex/*cytology/physiology;Cell Division;Bromodeoxyuridine;Astrocytes/cytology}, Number = {5439}, Organization = {Department of Psychology, Princeton University, Princeton, NJ 08544, USA. goulde\@princeton.edu}, Pages = {548-52.}, Title = {Neurogenesis in the neocortex of adult primates}, Uuid = {F334DD1F-CDEF-11D9-B244-000D9346EC2A}, Volume = {286}, Year = {1999}, url = {papers/Gould_Science1999.pdf}} @article{Gozlan:2003, Abstract = {In hippocampal CA1 pyramidal neurons, GABAergic synapses are established before glutamatergic synapses. GABAergic interneurons should therefore develop and acquire synapses at an earlier stage to provide the source for GABAergic synapses. We now report that this is indeed the case. At birth and in utero, when nearly all pyramidal neurons are not yet functional, most interneurons have already either GABAergic only or GABAergic and glutamatergic postsynaptic currents. At birth, the morphological maturation of interneurons parallels their individual functional responses. In addition, the formation of functional interneurons types appears to be a sequential process. Interneurons that innervate other interneurons acquire GABA(A) synapses before peridendritic interneurons, but also before perisomatic interneurons that are not yet functional at birth. Therefore, interneurons are the source and the targets of the first synapses formed in the developing circuit. Since GABA was shown to be excitatory in utero, interneurons provide all the excitatory drive at a time when the principal cells are silent. They could therefore play a central role in the formation of the cortical circuit at early developmental stages.}, Author = {Gozlan, Henri and Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Synapses;21 Epilepsy;Cell Differentiation;21 Neurophysiology;Comparative Study;Hippocampus;Neural Pathways;Rats;Rats, Wistar;Animals, Newborn;gamma-Aminobutyric Acid;Nerve Net;Animals;Patch-Clamp Techniques;24 Pubmed search results 2008;Interneurons;Receptors, GABA-A}, Medline = {22648209}, Month = {6}, Nlm_Id = {9110718}, Number = {6}, Organization = {INMED-INSERM U29, 163 route de Luminy, BP 13, 13273 Marseille cedex 9, France. gozlan\@inmed.univ.mrs.fr}, Pages = {684-92}, Pubmed = {12764045}, Title = {Interneurons are the source and the targets of the first synapses formed in the rat developing hippocampal circuit}, Uuid = {1032B05B-8991-4EB1-9BF5-76D64D453BC0}, Volume = {13}, Year = {2003}} @article{Gotz:2005, Abstract = {The fascinating question of how the enormous diversity of neuronal and glial cells in the cerebral cortex is generated during development was recently discussed at a meeting on cortical development and stem cells in Greece. What emerged from this meeting is an equally fascinating answer, namely that precursor diversity at rather early stages of development anticipates later cell type diversity.}, Author = {G{\"o}tz, Magdalena and Sommer, Lukas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Cerebral Cortex;review;Mice;10 Development;Neuroglia;Cilia;Morphogenesis;Humans;Variation (Genetics);Animals;Neurons;Microvilli}, Month = {8}, Nlm_Id = {8701744}, Number = {15}, Organization = {GSF, National Research Centre for Environment and Health, Institute for Stem Cell Research, Neuherberg/Munich, Germany. magdalena.goetz\@gsf.de}, Pages = {3327-32}, Pii = {132/15/3327}, Pubmed = {16014512}, Title = {Cortical development: the art of generating cell diversity}, Uuid = {AB3CFE2C-1F1E-4BCA-B98C-14D3358734F0}, Volume = {132}, Year = {2005}, url = {papers/Götz_Development2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.01931}} @article{Gotz:2006, Author = {G{\"o}tz, and Stricker,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {Magdalena G{\"o}tz is at the Institute for Stem Cell Research, GSFNational Research Institute for Environment and Health, Ingolst{\"a}dter Landstr. 1, 85764 Neuherberg, Germany and at the Department for Physiological Genomics, University of Munich, Schillerstr. 46, 80633 Munich, Germany. magdalena.goetz\@gsf.de.}, Pages = {470-472}, Pii = {nn0406-470}, Pubmed = {16568104}, Title = {Go with the flow: signaling from the ventricle directs neuroblast migration}, Uuid = {999460AB-12E2-423E-8584-51DD45D851D6}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0406-470}} @article{Gotz:2005a, Abstract = {Radial glial cells have been identified as a major source of neurons during development. Here, we review the evidence for the distinct "glial" nature of radial glial cells and contrast these cells with their progenitors, the neuroepithelial cells. Recent results also suggest that not only during neurogenesis in vivo, but also during the differentiation of cultured embryonic stem cells toward neurons, progenitors with clear glial antigenic characteristics act as cellular intermediates.}, Author = {G{\"o}tz, Magdalena and Barde, Yves-Alain A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cell Differentiation;Neuroglia;Stem Cells;Humans;Animals;Brain;Neurons;review}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Institute of Stem Cell Research, GSF-National Research Center for Environment and Health, Ingolst{\"a}dter Landstr. 1, D-85764 Neuherberg/Munich, Germany. magdalena.goetz\@gsf.de}, Pages = {369-72}, Pii = {S0896-6273(05)00348-X}, Pubmed = {15882633}, Title = {Radial glial cells defined and major intermediates between embryonic stem cells and CNS neurons}, Uuid = {AD8B2FA9-A3E5-11DA-AB00-000D9346EC2A}, Volume = {46}, Year = {2005}, url = {papers/Götz_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.012}} @article{Graber:2004, Abstract = {Penetrating cortical trauma frequently results in delayed development of epilepsy. In the rat undercut model of neocortical posttraumatic hyperexcitability, suppression of neuronal activity by exposing the injured cortex to tetrodotoxin (TTX) in vivo for approximately 2 weeks prevents the expression of abnormal hypersynchronous discharges in neocortical slices. We examined the relationship between neuronal activity during the latent period after trauma and subsequent expression of hyperexcitability by varying the timing of TTX treatment. Partially isolated islands of rat sensorimotor cortex were treated with Elvax polymer containing TTX to suppress cortical activity and slices obtained for in vitro experiments 10 to 15 days later. TTX treatment was either started immediately after injury and discontinued after a variable number of days or delayed for a variable time after the lesion was placed. Immediate treatment lasting only 2 to 3 days and treatment delayed up to 3 days prevented hyperexcitability. Thus, there is a critical period for development of hyperexcitability in this model that depends on cortical activity. We propose that the hyperexcitability caused by partial cortical isolation may represent an early stage of posttraumatic epileptogenesis. A hypothetical cascade of events leading to subsequent pathophysiological activity is likely initiated at the time of injury but remains plastic during this critical period.}, Author = {Graber, Kevin D. and Prince, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {Drug Administration Schedule;Electrophysiology;Animals;In Vitro;Rats;Comparative Study;Polyvinyls;21 Epilepsy;Neocortex;Epilepsy;Rats, Sprague-Dawley;Tetrodotoxin;Disease Models, Animal;Behavior, Animal;Critical Period (Psychology);Time Factors;Male;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Evoked Potentials, Somatosensory;21 Neurophysiology;Anesthetics, Local;24 Pubmed search results 2008;Immunohistochemistry;Electroencephalography;Research Support, Non-U.S. Gov't}, Month = {6}, Nlm_Id = {7707449}, Number = {6}, Organization = {Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA 94305-5300, USA. graberk\@stanford.edu}, Pages = {860-70}, Pubmed = {15174021}, Title = {A critical period for prevention of posttraumatic neocortical hyperexcitability in rats}, Uuid = {E3B67B95-FEDA-4E7D-8D93-24F5FFCD7730}, Volume = {55}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.20124}} @article{Grabowski:1995, Abstract = {The purpose of this work was to study if enriched housing conditions and fetal neocortical transplantation could enhance the functional outcome after focal brain ischemia in adult rats. The right middle cerebral artery (MCA) was ligated in 34 inbred, spontaneously hypertensive male rats, which were then randomly divided into three groups. Groups A and B were transferred to an enriched environment, i.e., a large cage with opportunities for various activities but not forcing the rats to do any particular tasks; group C was kept in standard laboratory cages. Three weeks after the MCA occlusion blocks of fetal neocortical tissue (Embryonic Day 17) were transplanted to the infarct cavity in groups B and C. Rats in group A (n = 11) and group B (n = 11) performed equally well and significantly better than rats in group C (n = 10) when placed on an inclined plane and when traversing a rotating pole 6 and 9 weeks after the MCA occlusion and in a leg placement test at 9, but not 6 and 12 weeks. Skilled forelimb function did not differ between the groups. Infarct size and thalamic atrophy did not differ between the groups and graft size was similar in group B and C. There was no correlation between infarct size and motor function in any of the tests in rats housed in an enriched environment. Since the environment can significantly alter functional outcome without reducing infarct size we suggest that more attention should be given to the role of the laboratory environment and to long term behavioral outcome in experimental stroke. 0014-4886 Journal Article}, Author = {Grabowski, M. and Sorensen, J. C. and Mattsson, B. and Zimmer, J. and Johansson, B. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Exp Neurol}, Keywords = {Cerebral Cortex/physiology/*transplantation;17 Transplant Regeneration;Thalamus/pathology;Rats;L abstr;*Social Environment;*Motor Activity;Brain Tissue Transplantation/*physiology;Cerebral Arteries;Cerebral Infarction/pathology/*physiopathology/therapy;Rats, Inbred SHR;Support, Non-U.S. Gov't;Animals;Male;Fetal Tissue Transplantation;*Psychomotor Performance}, Number = {1}, Organization = {Department of Neurology, Lund University Hospital, Sweden.}, Pages = {96-102}, Pubmed = {7601267}, Title = {Influence of an enriched environment and cortical grafting on functional outcome in brain infarcts of adult rats}, Uuid = {9336428B-EC80-11DA-8605-000D9346EC2A}, Volume = {133}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7601267}} @article{Gracia-Llanes:2003, Abstract = {This study investigates the targets of the population of vasoactive intestinal polypeptide (VIP)-containing deep short-axon cells of the rat olfactory bulb (OB), combining single- and double-immunocytochemical approaches under light and electron microscopy. It has been assumed that deep short-axon cells innervate granule cells in the mammalian OB, but their synaptic connectivity has not been demonstrated to date. Our results indicate that, instead of the accepted scheme of the bulbar circuitry, VIP-containing deep short-axon cells are gamma-aminobutyric acid (GABA)ergic interneurons specialized in the selective innervation of other GABAergic deep short-axon cells. Their axons contact with the perisomatic region and the dendritic portions of subsets of deep short-axon cells that contain VIP, calbindin D-28k and neuropeptide Y. Electron microscopy reveals axo-somatic and axo-dendritic symmetrical synapses from VIP-containing boutons. Taken altogether, our data show that the VIP-containing deep short-axon cells of the rat OB form an interneuronal network that modulates the function of other interneurons different from granule cells. They might be involved indirectly in the inhibition or disinhibition of principal cells or might participate in the generation of oscillatory activity and in the synchronization of populations of interneurons and, then, of principal cells. Present data demonstrate that modulation of the OB by local circuits is more complex than the simple inhibition from periglomerular cells and granule cells, and remark the importance of considering the contribution of other classes of GABAergic interneurons different from periglomerular cells and granule cells to the bulbar circuitry. 0953-816x Journal Article}, Author = {Gracia-Llanes, F. J. and Crespo, C. and Blasco-Ibanez, J. M. and Marques-Mari, A. I. and Martinez-Guijarro, F. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Eur J Neurosci}, Keywords = {Vasoactive Intestinal Peptide/*metabolism;13 Olfactory bulb anatomy;Animals;Olfactory Bulb/*cytology;Rats;Axons/classification/*metabolism/ultrastructure;Comparative Study;Female;Rats, Wistar;Support, Non-U.S. Gov't;Neurons/classification/*metabolism/ultrastructure;Calcium-Binding Protein, Vitamin D-Dependent/metabolism;Neuropeptide Y/metabolism;I pdf;Parvalbumins/metabolism;Immunohistochemistry;Microscopy, Electron;gamma-Aminobutyric Acid/metabolism}, Number = {7}, Organization = {Departamento de Biologia Celular, Facultad de Ciencias Biologicas, Universidad de Valencia, E-46100, Burjasot, Spain.}, Pages = {1751-63}, Pubmed = {14622210}, Title = {VIP-containing deep short-axon cells of the olfactory bulb innervate interneurons different from granule cells}, Uuid = {934A8DE9-ACEE-4FF8-BA96-53E29811A249}, Volume = {18}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14622210}} @article{Graeber:1990, Author = {Graeber, M. B. and Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0567-7556}, Journal = {Acta Histochem Suppl}, Keywords = {Neuroglia;Phagocytes;Nerve Tissue Proteins;Human;Not relevant;Biological Markers;11 Glia;Mesoderm;review, tutorial;Humans;Brain;Nervous System Diseases;review;Animals}, Medline = {91180327}, Nlm_Id = {0061372}, Organization = {Department of Neuromorphology, Max Planck Institute for Psychiatry, Martinsried, FRG.}, Pages = {157-60}, Pubmed = {2080239}, Title = {The third glial cell type, the microglia: cellular markers of activation in situ}, Uuid = {A55312EE-29EB-40D3-ACC2-77E7DE034494}, Volume = {38}, Year = {1990}} @article{Graeber:1989, Abstract = {Injection of ricin, the toxic lectin from Ricinus communis, into the rat facial nerve leads to rapid degeneration of motor neurons and concomitant proliferation and transformation of endogenous microglia into brain macrophages. Using [3H]-thymidine autoradiography, immunocytochemistry for microglial markers and electron microscopy, we could show that when ricin was administered together with the cytostatic drug adriamycin, the retrogradely transported adriamycin inhibits the macrophage response induced by toxic ricin. It is concluded that under conditions of neuronal degeneration, e.g., following ricin intoxication, brain macrophages are predominantly, if not exclusively, derived from endogenous microglia.}, Author = {Graeber, M. B. and Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Thymidine;Ricin;Glial Fibrillary Acidic Protein;Neuroglia;Nerve Degeneration;Rats;Microscopy, Electron;Doxorubicin;Not relevant;Cell Division;11 Glia;Macrophages;Male;Animals;Rats, Inbred Strains;Brain;Vimentin}, Medline = {89389837}, Nlm_Id = {0412041}, Number = {4}, Organization = {Abteilung f{\"u}r Neuromorphologie, Max-Planck-Institut f{\"u}r Psychiatrie, Martinsried, Federal Republic of Germany.}, Pages = {348-58}, Pubmed = {2782046}, Title = {Formation of microglia-derived brain macrophages is blocked by adriamycin}, Uuid = {0246CCE4-CFC4-4662-987C-B29882280F3C}, Volume = {78}, Year = {1989}} @article{Graeber:1993, Abstract = {An autopsy case of severe peripheral facial nerve paresis with disconnection of synapses from facial motor neurons is reported. A 77-year-old man presented with left-sided otitis media and subsequent development of facial nerve paresis. Three months later, the patient died of an acute gastrointestinal bleeding from a chronic duodenal ulcer. Gross inspection of the brain revealed non-stenosing arteriosclerotic vascular changes and a single small cystic lesion in the right putamen. Microscopically, marked chromatolytic changes were observed in the left facial nucleus. Immunocytochemistry for synaptophysin revealed a marked loss of afferent synaptic contacts from somatic and stem dendritic surface membranes of all chromatolytic motor neurons. Wrapping of a number of neurons by newly formed glial fibrillary acidic protein-positive astrocytic cell processes could be detected in the regenerating facial motor nucleus. In addition, expression of HLA-DR was increased on a small number of microglia and perivascular cells. These changes were absent from the contralateral, normal-appearing facial nucleus. To our knowledge, this case provides the first evidence for disconnection of synapses following peripheral nerve lesioning in humans. Occurrence of synaptic stripping is likely to explain nuclear hyperexcitability and failure of recovery of complex fine motor movements that are commonly observed following peripheral injury to the facial nerve.}, Author = {Graeber, M. B. and Bise, K. and Mehraein, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Synapses;Facial Paralysis;Glial Fibrillary Acidic Protein;Aged;Facial Nerve;Motor Neurons;Immunohistochemistry;HLA-DR Antigens;11 Glia;Synaptophysin;Male;Humans;case reports}, Medline = {94026193}, Nlm_Id = {0412041}, Number = {2}, Organization = {Institute of Neuropathology, Ludwig Maximilians University, Munich, Germany.}, Pages = {179-81}, Pubmed = {8213072}, Title = {Synaptic stripping in the human facial nucleus}, Uuid = {500C19CC-1037-4A06-92A5-53A9B95EA658}, Volume = {86}, Year = {1993}, url = {papers/Graeber_ActaNeuropathol(Berl)1993.PDF}} @article{Graeber:1990a, Abstract = {In recent years much progress has been made toward a better understanding of the nature and function of microglial cells. This review summarizes new developments and attempts to provide a perspective for future avenues to take in microglial research. Microglia are considered to play an active role in a variety of neurological diseases. Their function in forming a network of immune competent cells within the CNS is discussed.}, Author = {Graeber, M. B. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {1015-6305}, Journal = {Brain Pathol}, Keywords = {Research Support, Non-U.S. Gov't;Central Nervous System;Human;Mammals;Not relevant;11 Glia;Antigen-Presenting Cells;review, tutorial;Microglia;Humans;Support, Non-U.S. Gov't;Central Nervous System Diseases;Animals;review}, Medline = {94122928}, Month = {9}, Nlm_Id = {9216781}, Number = {1}, Organization = {Center for Neurologic Diseases, Harvard Medical School, Boston, MA.}, Pages = {2-5}, Pubmed = {1669689}, Title = {Microglia: immune network in the CNS}, Uuid = {66BC1F86-D771-4054-9C67-A34FE0B12EF3}, Volume = {1}, Year = {1990}} @article{Graeber:1998, Abstract = {Microglia represent a population of brain macrophage precursor cells which are intrinsic to the CNS parenchyma. Transection of the facial nerve in the newborn rat causes death of the affected motor neurons which is accompanied by massive activation of local microglia. Many of these cells develop into macrophages as can be shown by immunocytochemistry for OX-42 and ED1. Using the new polyclonal microglial marker ionized calcium binding adapter molecule 1, iba1, in combination with immunocytochemical double-labeling for the proliferating cell nuclear antigen (PCNA), or [3H]thymidine autoradiography, and confocal microscopy, qualitative as well as quantitative differences can be demonstrated between the newborn and the adult axotomized rat facial nucleus. While microglial cells are the only cell population which responds to axotomy by cell division in the adult facial nucleus, GFAP positive reactive astrocytes can be shown to undergo mitosis following axotomy in the newborn rat. Furthermore, ED1 immunoreactivity, early expression of MHC class II molecules and morphological transformation of microglia into macrophages can only be observed under conditions of neuronal degeneration, i.e., in the neonatal rat facial nucleus. Thus, the combination of cellular markers described here should be useful for studies employing the neonatal rat facial nucleus as an in vivo assay system to test the efficacy of neurotrophic factors.}, Author = {Graeber, M. B. and L{\'o}pez-Redondo, F. and Ikoma, E. and Ishikawa, M. and Imai, Y. and Nakajima, K. and Kreutzberg, G. W. and Kohsaka, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Nerve Degeneration;Animals;Macrophages;Rats;Major Histocompatibility Complex;Microglia;Proliferating Cell Nuclear Antigen;Rats, Wistar;11 Glia;Male;Animals, Newborn;Calcium-Binding Proteins;Axotomy;Age Factors;Motor Neurons;Cell Division;Facial Nerve;Research Support, Non-U.S. Gov't}, Medline = {99057683}, Month = {12}, Nlm_Id = {0045503}, Number = {2}, Organization = {Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried 82152, Germany.}, Pages = {241-53}, Pii = {S0006899398008592}, Pubmed = {9838143}, Title = {The microglia/macrophage response in the neonatal rat facial nucleus following axotomy}, Uuid = {738E60DA-A48C-4B9C-96C1-2DB2208AAD2F}, Volume = {813}, Year = {1998}} @article{Graeber:1993a, Author = {Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0722-5091}, Journal = {Clin Neuropathol}, Keywords = {Multiple Sclerosis;Central Nervous System;Blood-Brain Barrier;Encephalomyelitis, Autoimmune, Experimental;11 Glia;Microglia;Macrophages;Antigen-Presenting Cells;Humans;Animals}, Medline = {94037718}, Nlm_Id = {8214420}, Number = {5}, Organization = {Institute of Neuropathology, Ludwig Maximilians University, M{\"u}nchen, Germany.}, Pages = {296-7}, Pubmed = {8222403}, Title = {Microglia, macrophages and the blood-brain barrier}, Uuid = {8194C4B2-3B49-493C-ADE0-E1167601C7B1}, Volume = {12}, Year = {1993}} @article{Graeber:2002, Abstract = {Microglia have long been ignored by neurooncologists. This has changed with the realization that microglial cells not only occur within and around brain tumors but also contribute significantly to the actual tumor mass, notably in astrocytic gliomas. In addition, it has been speculated that microglia could play a role in the defense against neoplasms of the nervous system. However, the biological success of these tumors, i.e., their highly malignant behavior, indicates that natural microglial defense mechanisms do not function properly in astrocytomas. In fact, there is evidence that microglial behavior is controlled by tumor cells, supporting their growth and infiltration. This unexpected "Achilles heel" of microglial immune defense illustrates the risk of generalizing on the basis of a single aspect of microglial biology. Microglia are highly plastic cells, capable of exerting cytotoxic functions under conditions of CNS infections, but not necessarily during glioma progression. Thus, the suggestion that microglial activation through stimulation by cytokines (e.g., interferon-gamma) will benefit patients with brain tumors could prove fatally wrong. Therapeutic recruitment of microglia to treat such diffusely infiltrative brain tumors as astrocytic gliomas must be considered premature.}, Author = {Graeber, Manuel B. and Scheithauer, Bernd W. and Kreutzberg, Georg W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Cell Lineage;Immunotherapy;Antigen Presentation;Glioma;Cell Division;Cell Count;11 Glia;Microglia;Macrophages;Brain Neoplasms;review, tutorial;Neoplasm Invasiveness;Humans;Oligodendroglioma;review;Astrocytoma}, Medline = {22267070}, Month = {11}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Neuropathology, Faculty of Medicine, Imperial College, London, United Kingdom. m.graeber\@ic.ac.uk}, Pages = {252-9}, Pubmed = {12379912}, Title = {Microglia in brain tumors}, Uuid = {5368CC39-8682-42FF-BDAF-D0B22FCD262E}, Volume = {40}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10147}} @article{Graeber:1988, Abstract = {Unlike astrocytes and oligodendrocytes, microglia are extremely plastic making them the chameleon among the glial cells in the CNS. This great mutability of the microglial cell shape suggests the presence of an elaborate cytoskeleton which is demonstrated here by applying a new ultrastructural method. Electron microscopic immunocytochemistry shows the presence of vimentin at intermediate filament sites in reactive microglia stimulated by rat facial nerve axotomy. It is suggested that vimentin-expression may serve as a marker for activated states of microglia, including brain macrophages.}, Author = {Graeber, M. B. and Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Cytoskeleton;Facial Nerve;Immunohistochemistry;Microscopy, Electron;Rats;Not relevant;11 Glia;Microscopy, Fluorescence;Animals;Male;Rats, Inbred Strains;Vimentin}, Medline = {89055215}, Month = {8}, Nlm_Id = {0364620}, Number = {4}, Organization = {Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, FRG.}, Pages = {573-80}, Pubmed = {3193132}, Title = {The microglial cytoskeleton: vimentin is localized within activated cells in situ}, Uuid = {BE85D32B-F765-4F3A-96A2-FEF88797AAD4}, Volume = {17}, Year = {1988}} @article{Graeber:1990b, Abstract = {The results of the present study demonstrate that following lethal motor neuron injury microglia and perivascular cells, as well as brain macrophages derived from the latter two cell types, newly express antigens of the myelomonocytic lineage as recognized by the monoclonal antibodies ED1 and ED3. It is suggested that differences in the immunophenotype of resident brain macrophage precursor cells, i.e. microglia and perivascular cells, and macrophages occurring outside the central nervous system (CNS) may be explained by differences in local macrophage antigen expression rather than by a different embryological lineage. The new appearance of antigens common to peripheral macrophages on neural phagocytes in CNS lesions may therefore not necessarily imply that most or all of these cells are of recent blood origin.}, Author = {Graeber, M. B. and Streit, W. J. and Kiefer, R. and Schoen, S. W. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {T-Lymphocytes;Animals;Ricin;Macrophages;Rats;Brain;Rats, Inbred Strains;Doxorubicin;Not relevant;11 Glia;Male;Blood-Brain Barrier;Antigens;Antibodies, Monoclonal;Neuroglia;Motor Neurons;Microscopy, Electron;Stem Cells}, Medline = {90237177}, Month = {5}, Nlm_Id = {8109498}, Number = {2-3}, Organization = {Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, F.R.G.}, Pages = {121-32}, Pubmed = {2332482}, Title = {New expression of myelomonocytic antigens by microglia and perivascular cells following lethal motor neuron injury}, Uuid = {F636D1D7-2C50-4460-9353-140C75A975EC}, Volume = {27}, Year = {1990}} @article{Graeber:1992, Abstract = {The expression of major histocompatibility complex (MHC) class I and II antigens was studied in surgical and postmortem brain biopsy tissue using light and electron microscopic immunocytochemistry. In addition, monoclonal antibodies directed against human macrophages (EBM11) and alpha-smooth muscle actin were applied. It is shown that blood vessel-associated MHC class II immunoreactivity in histologically normal human brain can be localized to a distinct class of cells, termed perivascular cells, which share macrophage but not smooth muscle cell antigen. This immunophenotype, the location in the perivascular space as well as the morphology, frequency and tissue distribution distinguish perivascular cells from pericytes and intraparenchymal microglia. It is suggested that MHC class II positive perivascular cells are a normal constituent of the human cerebral microvasculature. The potential role of these cells in immunological reactions occurring at the blood-brain interface is discussed.}, Author = {Graeber, M. B. and Streit, W. J. and B{\"u}ringer, D. and Sparks, D. L. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Reference Values;Neuroglia;Research Support, Non-U.S. Gov't;Human;Immunohistochemistry;Histocompatibility Antigens Class II;Microscopy, Electron;Meninges;Antibodies, Monoclonal;11 Glia;Cerebrovascular Circulation;Not relevant;Humans;Support, Non-U.S. Gov't;Brain}, Medline = {92260276}, Month = {5}, Nlm_Id = {2985192R}, Number = {3}, Organization = {Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts.}, Pages = {303-11}, Pubmed = {1583535}, Title = {Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain}, Uuid = {3F0C3357-D672-41CF-92DE-93267C2B0E36}, Volume = {51}, Year = {1992}} @article{Graeber:1988a, Abstract = {Axotomy of the rat facial nerve leads to mitotic divisions of microglial cells without developing into phagocytes. In order to study the functional characteristics of those activated, i.e., proliferating but nonphagocytic, microglia we investigated the expression of monocyte/macrophage antigens by these cells. Our results show that activated microglia lack monocyte/macrophage antigens recognized by the monoclonal antibodies Ox-41, ED1, ED2, and Ki-M2R but express high levels of CR3 complement receptors in situ.}, Author = {Graeber, M. B. and Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Complement Activation;Receptors, Complement;Neuroglia;Facial Nerve;Rats;Antibodies, Monoclonal;Not relevant;11 Glia;Macrophages;Animals;Male;Rats, Inbred Strains}, Medline = {89111061}, Month = {9}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, Federal Republic of Germany.}, Pages = {18-24}, Pubmed = {3216409}, Title = {Axotomy of the rat facial nerve leads to increased CR3 complement receptor expression by activated microglial cells}, Uuid = {B19EB1D1-CC18-46F7-95F9-10C7F5183659}, Volume = {21}, Year = {1988}} @article{Graeber:1989a, Abstract = {A controversial, though fundamental, issue in neurobiology concerns the nature, origin, and function of brain macrophages. By immunocytochemical analysis using monoclonal antibodies directed against rat macrophage antigens, i.e., ED1-3, Ox-41, Ox-42, and Ki-M2R, we show that a group of perivascular cells located within the basal membrane of CNS blood vessels are immunoreactive. These cells, which resemble pericytes in terms of their anatomical distribution, are distinct from resting parenchymal microglia immunologically as well as morphologically. Our results demonstrate considerable heterogeneity in the immunophenotype of resident brain macrophages, which may be part of the immune-nervous system interface.}, Author = {Graeber, M. B. and Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Immunohistochemistry;Rats;Antibodies, Monoclonal;Get paper from library;Not relevant;11 Glia;Cerebrovascular Circulation;Macrophages;Blood Vessels;Animals;Brain;Rats, Inbred Strains;Male}, Medline = {89178769}, Month = {1}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Neuromorphology, Max Planck Institute for Psychiatry, Martinsried, Federal Republic of Germany.}, Pages = {103-6}, Pubmed = {2926837}, Title = {Identity of ED2-positive perivascular cells in rat brain}, Uuid = {2968D13D-5D96-4297-BBC2-46E050E54C05}, Volume = {22}, Year = {1989}} @article{Graeber:1994, Author = {Graeber, M. B. and Bise, K. and Mehraein, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {letter;Research Support, Non-U.S. Gov't;Genes, MHC Class II;Immunohistochemistry;Antibodies, Monoclonal;Biological Markers;11 Glia;Microglia;Humans;Nervous System Diseases}, Medline = {95107467}, Month = {8}, Nlm_Id = {7609829}, Number = {4}, Pages = {406-8}, Pubmed = {7808591}, Title = {CR3/43, a marker for activated human microglia: application to diagnostic neuropathology}, Uuid = {300AF937-DD52-4AEB-A08D-386544A47FE5}, Volume = {20}, Year = {1994}} @article{Graeber:1994a, Author = {Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Bibliography;11 Glia;Microglia;MEDLINE;Publishing}, Medline = {94352553}, Month = {4}, Nlm_Id = {7609829}, Number = {2}, Organization = {Molecular Neuropathology Laboratory, Ludwig-Maximilians-University, Munich.}, Pages = {215-6}, Pubmed = {8072671}, Title = {Development of the microglia literature}, Uuid = {C823B66A-486A-4225-84CE-14A4FA1C12A8}, Volume = {20}, Year = {1994}} @article{Graeber:1994b, Author = {Graeber, M. B. and Mehraein, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Pyramidal Cells;11 Glia;Microglia;Animals;Humans;Cerebral Cortex;Nervous System Diseases}, Medline = {94352529}, Month = {4}, Nlm_Id = {7609829}, Number = {2}, Organization = {Institute of Neuropathology, Ludwig-Maximilians-University, Munich.}, Pages = {178-80}, Pubmed = {8072649}, Title = {Microglial rod cells}, Uuid = {35B5680B-0D78-44A8-A7DA-7B6D83B78FE5}, Volume = {20}, Year = {1994}} @article{Graeber:1989b, Abstract = {Five monoclonal antibodies specific for rat monocytes/macrophages were used to characterize macrophages/microglia bulk isolated from neonatal and adult rat brain. The majority of brain macrophages was positive for all antibodies tested with minor differences between cultures derived from developing and mature central nervous tissue. These results contrast in vivo findings indicating that most antigens of peripheral macrophages are absent from resting, activated and phagocytic microglia in situ. We conclude that brain macrophages/microglia newly express antigens of the myelomonocytic lineage when in culture and that cultured brain macrophages may be derived from different types of precursor cells normally present within the CNS.}, Author = {Graeber, M. B. and Banati, R. B. and Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Monocytes;Rats;Phenotype;Antibodies, Monoclonal;Comparative Study;Not relevant;Antigens, Surface;11 Glia;Macrophages;Immunoenzyme Techniques;Animals;Cells, Cultured;Brain;Age Factors}, Medline = {90045041}, Month = {9}, Nlm_Id = {7600130}, Number = {3}, Organization = {Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, F.R.G.}, Pages = {241-6}, Pubmed = {2682390}, Title = {Immunophenotypic characterization of rat brain macrophages in culture}, Uuid = {D6B5752D-FD0B-4FE7-B25B-ED53E5648261}, Volume = {103}, Year = {1989}} @article{Graeber:1990c, Author = {Graeber, M. B. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Neuroglia;letter;Terminology;Blood-Brain Barrier;Human;Not relevant;11 Glia;comment;Humans;Brain}, Medline = {91020405}, Month = {9}, Nlm_Id = {7808616}, Number = {9}, Pages = {366}, Pubmed = {1699325}, Title = {Perivascular microglia defined}, Uuid = {9A5C5331-B860-4F0E-9407-D40EC2C66CB7}, Volume = {13}, Year = {1990}} @article{Graf:2004, Abstract = {Formation of synaptic connections requires alignment of neurotransmitter receptors on postsynaptic dendrites opposite matching transmitter release sites on presynaptic axons. beta-neurexins and neuroligins form a trans-synaptic link at glutamate synapses. We show here that neurexin alone is sufficient to induce glutamate postsynaptic differentiation in contacting dendrites. Surprisingly, neurexin also induces GABA postsynaptic differentiation. Conversely, neuroligins induce presynaptic differentiation in both glutamate and GABA axons. Whereas neuroligins-1, -3, and -4 localize to glutamate postsynaptic sites, neuroligin-2 localizes primarily to GABA synapses. Direct aggregation of neuroligins reveals a linkage of neuroligin-2 to GABA and glutamate postsynaptic proteins, but the other neuroligins only to glutamate postsynaptic proteins. Furthermore, mislocalized expression of neuroligin-2 disperses postsynaptic proteins and disrupts synaptic transmission. Our findings indicate that the neurexin-neuroligin link is a core component mediating both GABAergic and glutamatergic synaptogenesis, and differences in isoform localization and binding affinities may contribute to appropriate differentiation and specificity.}, Author = {Graf, Ethan R. and Zhang, XueZhao and Jin, Shan-Xue X. and Linhoff, Michael W. and Craig, Ann Marie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {gamma-Aminobutyric Acid;10 Development;Cell Differentiation;Animals;Synapses;Coculture Techniques;Protein Binding;Dystroglycans;Rats;Humans;Glutamic Acid;Mutation;COS Cells;Hippocampus;10 circuit formation;Dendrites;research support, u.s. gov't, p.h.s.;21 Neurophysiology;21 Activity-development;Mice;Amino Acid Motifs;24 Pubmed search results 2008;Membrane Proteins;Nerve Tissue Proteins;research support, u.s. gov't, non-p.h.s.}, Month = {12}, Nlm_Id = {0413066}, Number = {7}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.}, Pages = {1013-26}, Pii = {S0092867404011031}, Pubmed = {15620359}, Title = {Neurexins induce differentiation of GABA and glutamate postsynaptic specializations via neuroligins}, Uuid = {2E4CF3BE-DE11-47C1-9F45-72544CEA73BA}, Volume = {119}, Year = {2004}, url = {papers/Graf_Cell2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.11.035}} @article{Grandbarbe:2007, Abstract = {The Notch signaling pathway plays a crucial role in specifying cellular fate in metazoan development by regulating communication between adjacent cells. Correlative studies suggested an involvement of Notch in hematopoietic cell development. Here, we report that the Notch pathway is expressed and active in microglial cells. During inflammatory activation, the transcription of the Notch down-stream effector Hes1 is downregulated. When Notch1 transcription in microglia is inhibited, an upregulation of the expression of pro-inflammatory cytokines is observed. Notch stimulation in activated microglia, using a soluble form of its ligand Jagged1, induces a decrease in pro-inflammatory cytokines secretion and nitric oxide production as well as an increase in phagocytic activity. Notch-stimulation is accompanied by an increase in the rate of STAT3 phosphorylation and nuclear translocation. Our results show that the Notch pathway plays an important role in the control of inflammatory reactions in the CNS.}, Author = {Grandbarbe, Luc and Michelucci, Alessandro and Heurtaux, Tony and Hemmer, Karin and Morga, Eleonora and Heuschling, Paul}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {research support, non-u.s. gov't;11 Glia;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8806785}, Number = {15}, Organization = {Department of Life Sciences, University of Luxembourg, Luxembourg.}, Pages = {1519-30}, Pubmed = {17705199}, Title = {Notch signaling modulates the activation of microglial cells}, Uuid = {D083863B-CD51-4EE2-8AF7-D7A18CCFC68B}, Volume = {55}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20553}} @article{Gravel:1993, Abstract = {The Cas-Br-E murine leukemia virus (MuLV) induces a progressive hindlimb paralysis accompanied by a spongiform myeloencephalopathy in susceptible mice. In order to better understand the pathological process leading to these neurodegenerative lesions, we have investigated the nature of the cell type(s) infected by the virus during the course of the disease in CFW/D and SWR/J mice. For this purpose, we used in situ hybridization with virus-specific probes in combination with cell-type-specific histochemical (lectin) and immunological markers as well as morphological assessment. In the early stage of infection, endothelial cells represented the main cell type expressing viral RNA in the central nervous system (CNS). With disease progression and the appearance of lesions, microglial cells became the major cell type infected, accounting for up to 65\%of the total infected cell population in diseased areas. Morphologically, these cells appeared activated and were frequently found in clusters. Infection and activation of microglial cells were almost exclusively restricted to diseased regions of the CNS. Neurons in diseased regions were not discernibly infected with virus at either early or late times of disease progression. Similarly, the proportion of infected astrocytes was typically <1\%. Although some endothelial cells and oligodendrocytes were infected by the virus, their infection was not limited to diseased CNS regions. These results are consistent with a model of indirect motor neuron degeneration, subsequent to the infection of nonneuronal CNS cells and especially of microglial cells. Infected microglial cells may play a role in the disease process by releasing not only virions or viral env-gene-encoded gp70 proteins but also other factors which may be directly or indirectly toxic to neurons. Parallels between microglial cell infection by MuLV and by lentiviruses, and specifically by human immunodeficiency virus, are discussed.}, Author = {Gravel, C. and Kay, D. G. and Jolicoeur, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {In Situ Hybridization;Neurons;Mice, Inbred Strains;Oligodendroglia;Central Nervous System;Nerve Degeneration;Astrocytes;Endothelium;Not relevant;11 Glia;Microglia;Paralysis;Animals;Mice;Leukemia Virus, Murine;Prion Diseases;Support, Non-U.S. Gov't}, Medline = {94016849}, Month = {11}, Nlm_Id = {0113724}, Number = {11}, Organization = {Laboratory of Molecular Biology, Institut de Recherches Cliniques de Montr{\'e}al, Quebec, Canada.}, Pages = {6648-58}, Pubmed = {8411367}, Title = {Identification of the infected target cell type in spongiform myeloencephalopathy induced by the neurotropic Cas-Br-E murine leukemia virus}, Uuid = {175F8E91-1868-421A-8480-DCC349AA0A15}, Volume = {67}, Year = {1993}} @article{Gray:1998, Abstract = {Granule cell progenitors in the dentate gyrus of the hippocampal formation have the unusual capacity to be able to divide in the brains of adult rats and primates. The basal proliferation rate of granule cell progenitors in the adult rat is low compared with development, however, it is possible that this rate may become significantly altered under pathological conditions such as epilepsy. We have investigated whether the proliferation of granule cell progenitors is increased in adult rats in a model of temporal lobe epilepsy, by using systemic bromodeoxyuridine injections to label dividing cells. We report here for the first time that granule cell neurogenesis is increased bilaterally 1 week after a single unilateral intracerebroventricular injection of kainic acid. Bromodeoxyuridine labeled neurons increased at least 6-fold on the side ipsilateral to the kainic acid injection compared to controls, but significantly, were also increased, by at least 3-fold on the side contralateral to the injection. The dividing cells in the subgranular zone were identified as neurons since they expressed Class III beta tubulin but not glial fibrillary acidic protein.}, Author = {Gray, W. P. and Sundstrom, L. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Brain Res}, Keywords = {Kainic Acid/*pharmacology;Rats;Neurons/*cytology;Fluorescent Antibody Technique;Excitatory Amino Acid Agonists/*pharmacology;Animal;Neuroglia/chemistry;Glial Fibrillary Acidic Protein/analysis;Dentate Gyrus/*cytology/drug effects;Cell Count;Rats, Wistar;Stem Cells/*cytology;Antimetabolites;Male;Injections, Intraventricular;Support, Non-U.S. Gov't;D-8;06 Adult neurogenesis injury induced;Epilepsy/chemically induced/physiopathology;Bromodeoxyuridine;Cell Division/drug effects}, Number = {1-2}, Organization = {Department of Clinical Neurosciences, University of Southampton, Tremona Rd., Southampton SO16 6YD, UK.}, Pages = {52-9.}, Title = {Kainic acid increases the proliferation of granule cell progenitors in the dentate gyrus of the adult rat}, Uuid = {A1B511F1-1FFE-485A-B5EC-7D8A50459DB1}, Volume = {790}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9593820%20http://www.elsevier.com:80/cgi-bin/cas/tree/store/bres/cas_sub/browse/browse.cgi?year=1998&volume=790&issue=1-2&aid=14397}} @article{Gray:2006, Abstract = {Most excitatory synapses terminate on dendritic spines. Spines vary in size, and their volumes are proportional to the area of the postsynaptic density (PSD) and synaptic strength. PSD-95 is an abundant multi-domain postsynaptic scaffolding protein that clusters glutamate receptors and organizes the associated signaling complexes. PSD-95 is thought to determine the size and strength of synapses. Although spines and their synapses can persist for months in vivo, PSD-95 and other PSD proteins have shorter half-lives in vitro, on the order of hours. To probe the mechanisms underlying synapse stability, we measured the dynamics of synaptic PSD-95 clusters in vivo. Using two-photon microscopy, we imaged PSD-95 tagged with GFP in layer 2/3 dendrites in the developing (postnatal day 10-21) barrel cortex. A subset of PSD-95 clusters was stable for days. Using two-photon photoactivation of PSD-95 tagged with photoactivatable GFP (paGFP), we measured the time over which PSD-95 molecules were retained in individual spines. Synaptic PSD-95 turned over rapidly (median retention times tau(r) is approximately 22-63 min from P10-P21) and exchanged with PSD-95 in neighboring spines by diffusion. PSDs therefore share a dynamic pool of PSD-95. Large PSDs in large spines captured more diffusing PSD-95 and also retained PSD-95 longer than small PSDs. Changes in the sizes of individual PSDs over days were associated with concomitant changes in PSD-95 retention times. Furthermore, retention times increased with developmental age (tau(r) is approximately 100 min at postnatal day 70) and decreased dramatically following sensory deprivation. Our data suggest that individual PSDs compete for PSD-95 and that the kinetic interactions between PSD molecules and PSDs are tuned to regulate PSD size.}, Author = {Gray, Noah W. and Weimer, Robby M. and Bureau, Ingrid and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:22 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {Pregnancy;Tissue Distribution;Animals;Synapses;Protein Binding;Neocortex;Models, Biological;Female;Neurons, Afferent;Mice, Inbred C57BL;research support, non-u.s. gov't;Time Factors;Embryo;21 Neurophysiology;21 Circuit structure-function;Intracellular Signaling Peptides and Proteins;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Membrane Proteins;Nerve Tissue Proteins;Models, Neurological}, Month = {11}, Nlm_Id = {101183755}, Number = {11}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.}, Pages = {e370}, Pii = {06-PLBI-RA-1140R2}, Pubmed = {17090216}, Title = {Rapid redistribution of synaptic PSD-95 in the neocortex in vivo}, Uuid = {9AA08CE5-2FFD-49AD-A449-D43F70B52439}, Volume = {4}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0040370}} @article{Graziadei:1979a, Abstract = {The neurogenetic process leading to the formation of primary sensory neurons persists into adult life in the olfactory epithelium of mammals. The morphological stages of maturation and ageing of this exceptional neuron have been described both at light and electron microscopical levels. For descriptive purposes the neural elements have been classified as: (1) basal cells proper, (2) globose basal cells, and (3) neurons. Intermediate stages, however, have been identified. Autoradiographic observations complement the morphological studies and provide a time sequence of the morphological stages leading to the mature neurons. A typical columnar arrangement of the sensory neurons has been described. Furthermore, active and quiescent zones have been recognized in the neuroepithelium. In the active zones the neurogenetic process is vigorous, and the zones are characterized by the presence of immature elements. However, in the quiescent zones there exists a population of mature elements while immature neurons are sparse.}, Author = {Graziadei, P. P. and Graziadei, G. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurocytol}, Keywords = {Axons/cytology;Cell Differentiation;Cell Nucleus/ultrastructure;Rats;Olfactory Mucosa/*cytology/innervation;Regeneration;Animal;Neurons/*cytology;Support, U.S. Gov't, Non-P.H.S.;Cytoplasm/ultrastructure;Mitosis;I abstr;Mice;Support, U.S. Gov't, P.H.S.;13 Olfactory bulb anatomy;Organoids/ultrastructure;Dendrites/cytology}, Number = {1}, Pages = {1-18.}, Title = {Neurogenesis and neuron regeneration in the olfactory system of mammals. I. Morphological aspects of differentiation and structural organization of the olfactory sensory neurons}, Uuid = {B2E24AC4-594A-4984-9514-42698A180555}, Volume = {8}, Year = {1979}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=438867}} @article{Graziadei:1979, Abstract = {This report describes the retrograde degeneration affecting olfactory sensory neurons of rats after severance of their axons and illustrates the reconstitution of new neurons originating from stem cells located at the base of the olfactory neuroepithelium. Degeneration of the mature, axotomized neurons, signalled by an increased electron density of their cytoplasmic matrix and by the appearance of lipofuscin-like granules, can be detected in the neuroepithelium as early as 24 h after surgery and becomes conspicuous between the second and the third day. Degenerating neurons can be observed in decreasing number up to the tenth post-operative day. They are removed by macrophages which invade the epithelium. The reconstitution of new neurons begins to occur after eight days, when the stem cells undergo vigorous mitotic activity and differentiate into neurons. The morphology of the reconstituted neurons has been described in detail at different stages of their maturation. After 30 days, the olfactory epithelium appears similar to controls. On the basis of both morphological (in rats) and autoradiographic ( in mice) observations, the basal cells have been recognized as stem cells of the olfactory neurons.}, Author = {Graziadei, G. A. and Graziadei, P. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurocytol}, Keywords = {Cell Differentiation;*Nerve Degeneration;Rats;Vacuoles/ultrastructure;Olfactory Nerve/*cytology/physiology;Animal;Cytoplasm/ultrastructure;Support, U.S. Gov't, Non-P.H.S.;I abstr;Mitosis;Epithelium/cytology;*Nerve Regeneration;Male;Neurons/*physiology/ultrastructure;13 Olfactory bulb anatomy}, Number = {2}, Pages = {197-213.}, Title = {Neurogenesis and neuron regeneration in the olfactory system of mammals. II. Degeneration and reconstitution of the olfactory sensory neurons after axotomy}, Uuid = {6D5ED02A-03F6-48EB-B0E7-F0FF67A95B91}, Volume = {8}, Year = {1979}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=469573}} @article{Graziadei:1986, Author = {Graziadei, P. P. and Monti Graziadei, G. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuroscience}, Keywords = {I;Rats;Cerebral Cortex/transplantation;Microscopy, Electron;Synapses/physiology/ultrastructure;Animal;Support, U.S. Gov't, Non-P.H.S.;Olfactory Bulb/*anatomy &histology/growth &development/ultrastructure;Support, U.S. Gov't, P.H.S.;Morphogenesis;Xenopus laevis;13 Olfactory bulb anatomy;Cerebellar Cortex/transplantation}, Number = {4}, Pages = {1025-35.}, Title = {Principles of organization of the vertebrate olfactory glomerulus: an hypothesis}, Uuid = {F1B99903-5A1B-4440-B939-CE4320A87C58}, Volume = {19}, Year = {1986}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3822113}} @article{Graziadei:1978, Abstract = {We removed the right olfactory bulb in neonatal mice, leaving the bulb on the left side intact as an internal control. At 5 days of survival time, we observed that the right cerebral hemisphere was displaced forward to occupy the region made vacant by removal of the bulb. The frontal cortex was, consequently, in close proximity to the lamina cribrosa. As a result of bulb ablation and severance of the fila olfactoria, the sensory perikarya underwent total retrograde degeneration, which peaked at 8 days. New neurons differentiated in the neuroepithelium from basal stem cells and, at 30 days of survival, mature sensory neurons were reconstituted. These new elements sent their axons through the lamina cribrosa to reach the protruding cerebral hemisphere, penetrating it and forming glomeruli-like structures directly in the host tissue. The "glomerulization"of the sensory fibers persisted and actually expanded between 60 and 120 days. The new glomeruli were organized intimately within the brain tissue, and large neurons of the cortex were observed to be in close proximity. Ultrastructural observations of the newly formed glomeruli demonstrated that typical sensory axon terminals profusely branched and synapsed with unidentified postsynaptic processes that penetrated the glomeruli from the surrounding cerebral tissue. 0027-8424 Journal Article}, Author = {Graziadei, P. P. and Levine, R. R. and Graziadei, G. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Synapses;Animals, Newborn;Cell Differentiation;13 Olfactory bulb anatomy;Time Factors;Support, U.S. Gov't, Non-P.H.S.;Telencephalon/*physiology;I abstr;Olfactory Bulb/*physiology;Animals;*Nerve Regeneration;Mice;Axons/physiology;Support, U.S. Gov't, P.H.S.}, Number = {10}, Pages = {5230-4}, Pubmed = {283428}, Title = {Regeneration of olfactory axons and synapse formation in the forebrain after bulbectomy in neonatal mice}, Uuid = {B4CF30B5-354C-4254-9D20-9A780D9852E0}, Volume = {75}, Year = {1978}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=283428}} @article{Green:2000, Author = {Green, D. R. and Beere, H. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Nature}, Keywords = {07 Excitotoxicity Apoptosis;Human;Dendritic Cells/physiology;*Apoptosis;Phosphatidylserines/physiology;Histocompatibility Antigens Class I/physiology;Macrophages/*physiology;Receptors, Cell Surface/*physiology;Necrosis;E-12;T-Lymphocytes/physiology;Phagocytosis;Major Histocompatibility Complex;Self Tolerance}, Number = {6782}, Pages = {28-9.}, Title = {Apoptosis. Gone but not forgotten}, Uuid = {3018653F-A538-4EA1-8BDC-A2091B4F65D2}, Volume = {405}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10811203}} @article{Green:2006, Abstract = {To prevent duplication or loss of genomic regions during DNA replication, it is essential that the entire genome is copied precisely once every S phase. Cells achieve this by mutually exclusive regulation of origin firing and licensing. A crucial protein that is involved in origin licensing is chromatin licensing and DNA replication factor 1 (CDT1) and, therefore, activity of this protein must be strictly controlled. Four recent articles have demonstrated that proliferating cell nuclear antigen (PCNA), an essential sliding clamp used in replication and DNA repair, has a crucial role in this process by mediating the proteasomal degradation of CDT1.}, Author = {Green, Catherine M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1471-4914}, Journal = {Trends Mol Med}, Keywords = {Models, Biological;DNA-Binding Proteins;Cell Cycle Proteins;DNA Damage;Xenopus Proteins;Proteasome Endopeptidase Complex;Proliferating Cell Nuclear Antigen;Cell Cycle;Animals;Humans;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {100966035}, Number = {10}, Organization = {Genome Damage and Stability Centre, University of Sussex, Brighton, BN19RQ, UK. c.m.green\@sussex.ac.uk}, Pages = {455-8}, Pii = {S1471-4914(06)00173-0}, Pubmed = {16931160}, Title = {One ring to rule them all? Another cellular responsibility for PCNA}, Uuid = {A1C10A2F-941E-4D81-9EB7-164317B0DF2E}, Volume = {12}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.molmed.2006.08.004}} @article{Greenberg:2008, Abstract = {It is unclear how the complex spatiotemporal organization of ongoing cortical neuronal activity recorded in anesthetized animals relates to the awake animal. We therefore used two-photon population calcium imaging in awake and subsequently anesthetized rats to follow action potential firing in populations of neurons across brain states, and examined how single neurons contributed to population activity. Firing rates and spike bursting in awake rats were higher, and pair-wise correlations were lower, compared with anesthetized rats. Anesthesia modulated population-wide synchronization and the relationship between firing rate and correlation. Overall, brain activity during wakefulness cannot be inferred using anesthesia.}, Author = {Greenberg, David S. and Houweling, Arthur R. and Kerr, Jason N. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Wakefulness;Rhodamines;Rats, Long-Evans;Animals;Rats;Algorithms;Egtazic Acid;Diagnostic Imaging;Rats, Sprague-Dawley;Anesthesia;Calcium;research support, non-u.s. gov't;Animals, Newborn;Action Potentials;Statistics, Nonparametric;Neurons;Photons;24 Pubmed search results 2008;Visual Cortex;Spectrum Analysis;Electroencephalography}, Month = {7}, Nlm_Id = {9809671}, Number = {7}, Organization = {Department of Cell Physiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.}, Pages = {749-51}, Pii = {nn.2140}, Pubmed = {18552841}, Title = {Population imaging of ongoing neuronal activity in the visual cortex of awake rats}, Uuid = {71F177E4-D403-4441-9EAF-39E5D84AD825}, Volume = {11}, Year = {2008}, url = {papers/Greenberg_NatNeurosci2008.pdf}, Bdsk-File-2 = {papers/Greenberg_NatNeurosci2008a.pdf}, Bdsk-File-3 = {papers/Greenberg_NatNeurosci2008.wmv}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2140}} @article{Greenberger:1980, Abstract = {Infection in vitro of freshly explanted N:NIH(S) mouse bone marrow with ectopic murine leukemia viruses produced an increase over control uninfected cultures in the 50 or more cell granulocyte-macrophage (GM) colonies and 10-49 cell clusters detected after 7 days of incubation in 0.3\%agar at 37 degrees C and 7\%CO2. This effect was observed only at plating densities above 5.0 X 10(4) cells/ml and was not observed with macrophage-depleted populations of colony-forming units of GM progenitor cells (GM-CFUc) purified by isopyknic density gradient centrifugation of nonadherent cells harvested from long-term bone marrow cultures. Fewer virus-infected, compared to uninfected, peritoneal exudate macrophages were required to stimulate the same number of GM colonies and clusters in a given number of purified GM-CFUc. In contrast, murine leukemia virus infection of T-lymphocytes or NIH/3T3 embryo fibroblasts did not stimulate release of GM-CFUc coloney-stimulating factor (CSF). Single Cell suspensions of virus-infected freshly explanted whole bone marrow grown in CSF concentrated from L929 or WEHI-3 cell-conditioned medium produced more GM-CFUc colonies and GM clusters/1 X 10(5) cells compared to single cell suspensions of uninfected marrow. This phenomenon suggests that the colonoy-forming cells responding to CSF from virus-infected marrow may have been different from those responding to L929 or WEHI-3 cell CSF. The data indicate that increased granulopoiesis observed following retrovirus infection in vivo or in long-term marrow cultures was attributable in part to virus stimulation of production of CSF by adherent marrow stromal cells including macrophages.}, Author = {Greenberger, J. S. and Wroble, L. M. and Sakakeeny, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0027-8874}, Journal = {J Natl Cancer Inst}, Keywords = {15 Retrovirus mechanism;24 Pubmed search results 2008;Mice, Inbred BALB C;Bone Marrow;L Cells (Cell Line);Research Support, U.S. Gov't, P.H.S.;Granulocytes;Mice, Inbred C57BL;Colony-Forming Units Assay;Macrophages;Colony-Stimulating Factors;Tumor Virus Infections;Cells, Cultured;Animals;Leukemia Virus, Murine;Mice, Nude;Mice}, Medline = {81028739}, Month = {10}, Nlm_Id = {7503089}, Number = {4}, Pages = {841-51}, Pubmed = {6252364}, Title = {Murine leukemia viruses: induction of macrophage production of granulocyte-macrophage colony-stimulating factor in vitro}, Uuid = {6694A74B-4328-11DB-A5D2-000D9346EC2A}, Volume = {65}, Year = {1980}} @article{Gregg:2003, Abstract = {Radial glial cells (RGCs), a transient cell population present only in the developing CNS, function both as precursor cells and as scaffolds to support neuron migration. Their cellular origin, however, is not understood. In the present study, we tested the hypothesis that functional RGCs can be generated by multipotent neural stem cells. Embryonic forebrain neural stem cells were studied in vitro to identify putative signals that promote the generation and differentiation of functional RGCs, determined by their ability to support neuronal migration. Epidermal growth factor receptor signaling was sufficient to regulate both the generation and differentiation of morphologically, antigenically, and functionally defined RGCs. In contrast, fibroblast growth factor-2 promoted the generation of RGCs but was unable to support their differentiation. Although RGCs are not normally present in the adult brain, epidermal growth factor stimulated adult forebrain neural stem cells to generate RGCs in vitro and functional RGCs within the adult forebrain subependyma in vivo. Surprisingly, epidermal growth factor receptor signaling also promoted adult forebrain ependymal cells to dedifferentiate and adopt a radial morphology in vivo. These results suggest that neural stem cells can give rise to RGCs and that RGC-guided neuronal migration can be recapitulated in the adult CNS. 1529-2401 Journal Article}, Author = {Gregg, C. and Weiss, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {J Neurosci}, Keywords = {Ependyma/cytology;Cell Differentiation;Animals;Cells, Cultured;Neuroglia/*cytology/physiology;Central Nervous System/cytology;Cell Movement;Receptor, Epidermal Growth Factor/metabolism;Male;Microscopy, Fluorescence;Stem Cells/cytology/drug effects/*physiology;Epidermal Growth Factor/pharmacology;Prosencephalon/*cytology/*embryology;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Fibroblast Growth Factor 2/pharmacology;Mice;C pdf}, Number = {37}, Organization = {Genes &Development Research Group, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1.}, Pages = {11587-601}, Pubmed = {14684861}, Title = {Generation of functional radial glial cells by embryonic and adult forebrain neural stem cells}, Uuid = {296B85F4-CE6D-4DC7-923D-73812A90B495}, Volume = {23}, Year = {2003}, url = {papers/Gregg_JNeurosci2003.pdf}} @article{Grenier:2001, Abstract = {Field potentials from different neocortical areas and intracellular recordings from areas 5 and 7 in acutely prepared cats under ketamine-xylazine anesthesia and during natural states of vigilance in chronic experiments, revealed the presence of fast oscillations (80-200 Hz), termed ripples. During anesthesia and slow-wave sleep, these oscillations were selectively related to the depth-negative (depolarizing) component of the field slow oscillation (0.5-1 Hz) and could be synchronized over ~10 mm. The dependence of ripples on neuronal depolarization was also shown by their increased amplitude in field potentials in parallel with progressively more depolarized values of the membrane potential of neurons. The origin of ripples was intracortical as they were also detected in small isolated slabs from the suprasylvian gyrus. Of all types of electrophysiologically identified neocortical neurons, fast-rhythmic-bursting and fast-spiking cells displayed the highest firing rates during ripples. Although linked with neuronal excitation, ripples also comprised an important inhibitory component. Indeed, when regular-spiking neurons were recorded with chloride-filled pipettes, their firing rates increased and their phase relation with ripples was modified. Thus besides excitatory connections, inhibitory processes probably play a major role in the generation of ripples. During natural states of vigilance, ripples were generally more prominent during the depolarizing component of the slow oscillation in slow-wave sleep than during the states of waking and rapid-eye movement (REM) sleep. The mechanisms of generation and synchronization, and the possible functions of neocortical ripples in plasticity processes are discussed.}, Author = {Grenier, F. and Timofeev, I. and Steriade, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Electrophysiology;Animals;Anesthetics, Inhalation;Sleep, REM;Xylazine;research support, u.s. gov't, p.h.s. ;Neocortex;Ketamine;Epilepsy;Anesthetics, Dissociative;Periodicity;Sleep;research support, non-u.s. gov't ;Action Potentials;Adrenergic alpha-Agonists;21 Neurophysiology;Neurons;Halothane;Arousal;24 Pubmed search results 2008;Cats;Electroencephalography}, Month = {10}, Nlm_Id = {0375404}, Number = {4}, Organization = {Laboratoire de Neurophysiologie, Facult{\'e} de M{\'e}decine, Universit{\'e} Laval, Quebec G1K 7P4, Canada.}, Pages = {1884-98}, Pubmed = {11600648}, Title = {Focal synchronization of ripples (80-200 Hz) in neocortex and their neuronal correlates}, Uuid = {15B29D64-39B3-465B-B3F2-B49A1AD48CDE}, Volume = {86}, Year = {2001}} @article{Gressens:1992, Abstract = {The origin of astrocytes of the mouse neocortex during the fetal and early postnatal periods as determined by immunocytological, autoradiographic, electron microscopic and antimitotic methods is described. Most astrocytes destined for the white matter and the infragranular cortical layers are derived from the transformation of radial glial cells between P0 and P10 with an inside-out pattern. This cell metamorphosis is not directly preceded by mitosis and involves the activation of the radial glial lysosomal apparatus. In opposition to recent hypotheses, our findings suggest that most astrocytes destined for the supragranular cortical layers are produced in the germinative zone after the migration of the infragranular neurons and themselves migrate afterwards to the upper cortex between E16 and the first postnatal days. These astrocytes do not display an intermediate stage of the radial glial cell and do not participate in the pattern of appearance of the deeper astrocytes. This second step of astrocytogenesis is a condition for normal cytoarchitectonic development and the maintenance of the supragranular layers, since the deprivation of the astrocytic equipment of the supragranular layers by an antimitotic drug drastically reduces the number of supragranular neurons. Using Smart Source Parsing}, Author = {Gressens, P. and Richelme, C. and Kadhim, H. J. and Gadisseux, J. F. and Evrard, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Biol Neonate}, Keywords = {G;Pregnancy;Thymidine/metabolism;Cell Movement/*physiology;Female;Animal;Glial Fibrillary Acidic Protein/analysis;Astrocytes/chemistry/*physiology/ultrastructure;Staining and Labeling;11 Glia;Support, Non-U.S. Gov't;Methylazoxymethanol Acetate;Mice;Cell Differentiation/physiology;Neurons/chemistry/*physiology/ultrastructure;Immunohistochemistry;Autoradiography;Cerebral Cortex/chemistry/*embryology/metabolism}, Number = {1}, Organization = {Laboratory of Developmental Neurology, University of Louvain Medical School, Brussels, Belgium.}, Pages = {4-24}, Title = {The germinative zone produces the most cortical astrocytes after neuronal migration in the developing mammalian brain}, Uuid = {004D588C-F899-4A42-8E29-A5090BF12A4A}, Volume = {61}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1373658}} @article{Griffith:2008, Author = {Griffith, Leslie C. and Rosbash, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9809671}, Number = {2}, Organization = {The authors are at the Department of Biology, MS008, Brandeis University, 415 South Street, Waltham, Massachusetts 02454, USA. griffith\@brandeis.edu or rosbash\@brandeis.edu.}, Pages = {123-4}, Pii = {nn0208-123}, Pubmed = {18227792}, Title = {Sleep: hitting the reset button}, Uuid = {BFB10AC0-8106-445E-8C1E-FFF3DE39ECE8}, Volume = {11}, Year = {2008}, url = {papers/Griffith_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0208-123}} @article{Griffiths:2001, Abstract = {The human genome contains many endogenous retroviral sequences, and these have been suggested to play important roles in a number of physiological and pathological processes. Can the draft human genome sequences help us to define the role of these elements more closely?}, Author = {Griffiths, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1465-6914}, Journal = {Genome Biol}, Keywords = {15 ERVs retroelements;Endogenous Retroviruses;Cell Fusion;Autoimmune Diseases;Gene Expression Regulation;Genome, Human;Trophoblasts;Neoplasms;15 Retrovirus mechanism;Humans;24 Pubmed search results 2008;review}, Medline = {21316070}, Nlm_Id = {100960660}, Number = {6}, Organization = {Wohl Virion Centre, Department of Immunology and Molecular Pathology, Windeyer Institute of Medical Sciences, University College London, Cleveland Street, London W1T 4JF, UK. d.j.griffiths\@ucl.ac.uk}, Pages = {REVIEWS1017}, Pubmed = {11423012}, Title = {Endogenous retroviruses in the human genome sequence}, Uuid = {833A2342-4326-11DB-A5D2-000D9346EC2A}, Volume = {2}, Year = {2001}, url = {papers/Griffiths_GenomeBiol2001.pdf}} @article{Grillner:2005, Abstract = {To understand the interface between global brain function and molecular neuroscience--that is, the microcircuit level--a major challenge. Such understanding is prerequisite if we are to account for neural function in cellular terms. Very few vertebrate microcircuits are yet understood because their analysis is demanding technically. In this review of the TINS Microcircuits Special Feature, we attempt to shed light on the problem by comparing the operation of four types of microcircuit, to identify common molecular and cellular components. Central pattern generator (CPG) networks underlying rhythmic movements and hippocampal microcircuits that generate gamma and theta rhythms are compared with the neocortical microcircuits used in cognitive tasks and a cerebellar network. The long-term goal is to identify the components of a molecular and synaptic tool kit for the design of different microcircuits.}, Author = {Grillner, Sten and Markram, Henry and De Schutter, Erik and Silberberg, Gilad and LeBeau, Fiona E. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Movement;21 Neurophysiology;Neural Networks (Computer);Hippocampus;Models, Neurological;Neural Pathways;Neocortex;21 Circuit structure-function;Nerve Net;Animals;Humans;Periodicity;review;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {7808616}, Number = {10}, Organization = {Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden. sten.grillner\@neuro.ki.se}, Pages = {525-33}, Pii = {S0166-2236(05)00211-0}, Pubmed = {16118022}, Title = {Microcircuits in action--from CPGs to neocortex}, Uuid = {4EB75DC2-72B7-454E-9EA7-558B9B2BB4A1}, Volume = {28}, Year = {2005}, url = {papers/Grillner_TrendsNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2005.08.003}} @article{Grimpe:2004, Abstract = {CNS lesions induce production of ECM molecules that inhibit axon regeneration. One major inhibitory family is the chondroitin sulfate proteoglycans (CSPGs). Reduction of their glycosaminoglycan (GAG) chains with chondroitinase ABC leads to increased axon regeneration that does not extend well past the lesion. Chondroitinase ABC, however, is unable to completely digest the GAG chains from the protein core, leaving an inhibitory "stub"carbohydrate behind. We used a newly designed DNA enzyme, which targets the mRNA of a critical enzyme that initiates glycosylation of the protein backbone of PGs, xylosyltransferase-1. DNA enzyme administration to TGF-beta-stimulated astrocytes in culture reduced specific GAG chains. The same DNA enzyme applied to the injured spinal cord led to a strong reduction of the GAG chains in the lesion penumbra and allowed axons to regenerate around the core of the lesion. Our experiments demonstrate the critical role of PGs, and particularly those in the penumbra, in causing regeneration failure in the adult spinal cord. 1529-2401 Journal Article}, Author = {Grimpe, B. and Silver, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {J Neurosci}, Keywords = {G, L pdf;11 Glia}, Number = {6}, Organization = {Case Western Reserve University, School of Medicine, Department of Neurosciences, Cleveland, Ohio 44106, USA. bxg15\@po.cwru.edu}, Pages = {1393-7}, Title = {A novel DNA enzyme reduces glycosaminoglycan chains in the glial scar and allows microtransplanted dorsal root ganglia axons to regenerate beyond lesions in the spinal cord}, Uuid = {BE5C7373-FDE5-4FF4-A7A1-BCF3A2FA0878}, Volume = {24}, Year = {2004}, url = {papers/Grimpe_JNeurosci2004.pdf}} @article{Grinstein:2005, Abstract = {Synchronous firing peaks at levels greatly exceeding background activity have recently been reported in neocortical tissue. A small subset of neurons is dominant in a large fraction of the peaks. To investigate whether this striking behavior can emerge from a simple model, we constructed and studied a model neural network that uses a modified Hopfield-type dynamical rule. We find that networks having a power-law ("scale-free") node degree distribution readily generate extremely large synchronous firing peaks dominated by a small subset of nodes, whereas random (Erd{\"o}s-R{\'e}nyi) networks do not. This finding suggests that network topology may play an important role in determining the nature and magnitude of synchronous neural activity.}, Author = {Grinstein, Geoffrey and Linsker, Ralph}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {20 Networks;Neural Networks (Computer);Stochastic Processes;Computer Simulation;comparative study;Synaptic Transmission;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7505876}, Number = {28}, Organization = {IBM Thomas J. Watson Research Center, 1101 Kitchawan Road & Route 134, PO Box 218, Yorktown Heights, NY 10598, USA.}, Pages = {9948-53}, Pii = {0504127102}, Pubmed = {15998732}, Title = {Synchronous neural activity in scale-free network models versus random network models}, Uuid = {9437DD75-5193-421F-8E35-6AB3E0823D01}, Volume = {102}, Year = {2005}, url = {papers/Grinstein_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0504127102}} @article{Grinvald:2005, Author = {Grinvald, Amiram}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {21 Neurophysiology;Action Potentials;Calcium;Diagnostic Imaging;21 Calcium imaging;Neocortex;Synaptic Transmission;Nerve Net;Humans;comment;24 Pubmed search results 2008;Neurons;23 Technique}, Month = {10}, Nlm_Id = {7505876}, Number = {40}, Organization = {Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel. amiram.grinvald\@weizmann.ac.il}, Pages = {14125-6}, Pii = {0506755102}, Pubmed = {16189023}, Title = {Imaging input and output dynamics of neocortical networks in vivo: exciting times ahead}, Uuid = {7DEB4EFB-C8BD-4EC7-8F30-BA9190646B3F}, Volume = {102}, Year = {2005}, url = {papers/Grinvald_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0506755102}} @article{Gripon:1988, Abstract = {We investigated the possibility of infecting normal adult human hepatocytes maintained in pure cultures or in cocultures with hepatitis B virus (HBV). Several assays with different infectious sera and hepatocyte populations from various donors identified only limited HBV replication, with significant variations from one cell preparation to another. The addition of 1.5\%dimethyl sulfoxide to the culture medium markedly enhanced the infection process. Indeed, hepatitis B e antigen secretion, the appearance of both HBV DNA replicative forms and major HBV transcripts, and the release of complete HBV particles into the medium were demonstrated. It is possible that the significant increase in intracellular HBV DNA in dimethyl sulfoxide-treated cells was related to enhanced adsorption of the virus. When viral particles produced by a transfected HepG2 cell line were used to infect normal hepatocytes, the same results were obtained. In addition, comparative assays with hepatocytes from three different donors showed that although high amounts of intracellular viral DNA were found in all cases, viral replicative intermediates were visualized in only one case. These findings suggest that this HBV-producing cell line could serve as a reproducible source of infectious virus and that primary culturing of human hepatocytes represents a unique tool for analyzing intracellular regulating factors which, in addition to the penetration step, modulate HBV replication. 0022-538x Journal Article}, Author = {Gripon, P. and Diot, C. and Theze, N. and Fourel, I. and Loreal, O. and Brechot, C. and Guguen-Guillouzo, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Virol}, Keywords = {RNA, Viral/analysis/biosynthesis;Human;Cell Survival/drug effects;Liver/cytology/*microbiology;Hepatitis B Virus/drug effects/*growth &development;Cells, Cultured;Transfection;Virion/isolation &purification/pathogenicity;Centrifugation, Density Gradient;Kinetics;EE, DMSO, abstr;08 Aberrant cell cycle;Immunoblotting;Support, Non-U.S. Gov't;Culture Media/analysis/pharmacology;Virus Cultivation/*methods;Dimethyl Sulfoxide/*pharmacology;DNA, Viral/analysis/biosynthesis;Hepatitis B Surface Antigens/biosynthesis;Hepatitis B e Antigens/biosynthesis}, Number = {11}, Organization = {INSERM Unite 49, Hopital de Pontchaillou, Rennes, France.}, Pages = {4136-43}, Pubmed = {3172341}, Title = {Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide}, Uuid = {AB479F47-4284-452F-A2AF-2B423292A201}, Volume = {62}, Year = {1988}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3172341}} @article{Gritti:1996, Abstract = {It has been established that the adult mouse forebrain contains multipotential (neuronal/glial) progenitor cells that can be induced to proliferate in vitro when epidermal growth factor is provided. These cells are found within the subventricular zone of the lateral ventricles, together with other progenitor cell populations, whose requirements for proliferation remain undefined. Using basic fibroblast growth factor (bFGF), we have isolated multipotential progenitors from adult mouse striatum. These progenitors proliferate and can differentiate into cells displaying the antigenic properties of astrocytes, oligodendrocytes, and neurons. The neuron-like cells possess neuronal features, exhibit neuronal electrophysiological properties, and are immunoreactive for GABA, substance P, choline acetyl-transferase, and glutamate. Clonal analysis confirmed the multipotency of these bFGF-dependent cells. Most significantly, subcloning experiments demonstrated that they were capable of self-renewal, which led to a progressive increase in population size over serial passaging. These results demonstrate that bFGF is mitogenic for multipotential cells from adult mammalian forebrain that possess stem cell properties. 0270-6474 Journal Article}, Author = {Gritti, A. and Parati, E. A. and Cova, L. and Frolichsthal, P. and Galli, R. and Wanke, E. and Faravelli, L. and Morassutti, D. J. and Roisen, F. and Nickel, D. D. and Vescovi, A. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {J Neurosci}, Keywords = {Cell Differentiation/drug effects;Animals;Cells, Cultured;Stem Cells/cytology/*drug effects;Phenotype;Corpus Striatum/*cytology;C abstr;Support, Non-U.S. Gov't;Action Potentials;Cell Lineage;Neurotransmitters/metabolism;04 Adult neurogenesis factors;Neurons/cytology;Mice;Fibroblast Growth Factor 2/*pharmacology;Clone Cells;Biological Markers;Cell Division/drug effects;Neuroglia/cytology}, Number = {3}, Organization = {Laboratory of Cellular Neuropharmacology, National Neurological Institute C, Milan, Italy.}, Pages = {1091-100}, Pubmed = {8558238}, Title = {Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor}, Uuid = {D7078ABD-51BF-415B-B562-91C1FE08F6B8}, Volume = {16}, Year = {1996}, url = {papers/Gritti_JNeurosci1996}} @article{Gritti:1999, Abstract = {The subventricular zone (SVZ) of the adult mammalian forebrain contains kinetically distinct precursor populations that contribute new neurons to the olfactory bulb. Because among forebrain precursors there are stem-like cells that can be cultured in the presence of mitogens such as epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2), we asked whether distinct subsets of stem-like cells coexist within the SVZ or whether the proliferation of a single type of SVZ stem-like cell is controlled by several GFs. We show that the latter is the case. Thus cells isolated from the SVZ coexpress the EGF and FGF receptors; by quantitative analysis, the number of stem-like cells isolated from the SVZ by either FGF2 or EGF is the same, whereas no additive effect occurs when these factors are used together. Furthermore, short-term administration of high-dose [3H]thymidine in vivo depletes both the EGF- and FGF2-responsive stem-like cell populations equally, showing they possess closely similar proliferation kinetics and likely belong to the constitutively proliferating SVZ compartment. By subcloning and population analysis, we demonstrate that responsiveness to more than one GF endows SVZ cells with an essential stem cell feature, the ability to vary self-renewal, that was until now undocumented in CNS stem-like cells. The multipotent stem cell-like population that expands slowly in the presence of FGF2 in culture switches to a faster growth mode when exposed to EGF alone and expands even faster when exposed to both GFs together. Analogous responses are observed when the GFs are used in the reverse order, and furthermore, these growth rate modifications are fully reversible. 0270-6474 Journal Article}, Author = {Gritti, A. and Frolichsthal-Schoeller, P. and Galli, R. and Parati, E. A. and Cova, L. and Pagano, S. F. and Bjornson, C. R. and Vescovi, A. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Neurons/*cytology/drug effects/*physiology;Animals;Cells, Cultured;Stem Cells/*cytology/drug effects/physiology;C abstr;Kinetics;Fibroblast Growth Factor 2/*pharmacology/physiology;Receptor, Epidermal Growth Factor/*genetics/physiology;Receptor Protein-Tyrosine Kinases/*genetics/physiology;Corpus Striatum/cytology/physiology;Reverse Transcriptase Polymerase Chain Reaction;Support, Non-U.S. Gov't;Receptors, Fibroblast Growth Factor/*genetics/physiology;04 Adult neurogenesis factors;Mice;Epidermal Growth Factor/*pharmacology/physiology;Prosencephalon/*cytology/physiology;Cell Division/drug effects}, Number = {9}, Organization = {Laboratory of Neuropharmacology, National Neurological Institute C. Besta, Milan, Italy I-20133.}, Pages = {3287-97}, Pubmed = {10212288}, Title = {Epidermal and fibroblast growth factors behave as mitogenic regulators for a single multipotent stem cell-like population from the subventricular region of the adult mouse forebrain}, Uuid = {2F6D025D-5D42-46DF-A16E-0FD899702507}, Volume = {19}, Year = {1999}, url = {papers/Gritti_JNeurosci1999.pdf}} @article{Gritti:2002, Abstract = {The lateral walls of the forebrain lateral ventricles are the richest source of stem cells in the adult mammalian brain. These stem cells give rise to new olfactory neurons that are renewed throughout life. The neurons originate in the subventricular zone (SVZ), migrate within the rostral extension (RE) of the SVZ along the rostral migratory stream (RMS) within tube-like structures formed of glial cells, to eventually reach the olfactory bulb (OB). We demonstrate that, contrary to the current view, multipotential (neuronal-astroglial-oligodendroglial) precursors with stem cell features can be isolated not only from the SVZ but also from the entire RE, including the distal portion within the OB. Specifically, these stem cells do not derive from the migratory neuroblasts coming from the SVZ. Interestingly, stem cells isolated from the proximal RE generate significantly more oligodendrocytes, and those from the distal RE proliferate significantly more slowly than stem cells derived from the SVZ and other RE regions. These findings demonstrate that stem cells are not confined to the forebrain periventricular region and indicate that stem cells endowed with different functional characteristics occur at different levels of the SVZ-RE pathway. 1529-2401 Journal Article}, Author = {Gritti, A. and Bonfanti, L. and Doetsch, F. and Caille, I. and Alvarez-Buylla, A. and Lim, D. A. and Galli, R. and Verdugo, J. M. and Herrera, D. G. and Vescovi, A. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {J Neurosci}, Keywords = {Oligodendroglia/cytology;Animals;Cell Separation;Cells, Cultured;Olfactory Bulb/*cytology;Phenotype;Spheroids, Cellular/cytology;02 Adult neurogenesis migration;Neurons/classification/*cytology/metabolism;Time Factors;Cell Line/cytology;03 Adult neurogenesis progenitor source;BB pdf;Stem Cells/classification/*cytology/drug effects;Support, Non-U.S. Gov't;Clone Cells/classification/cytology/drug effects;Growth Substances/pharmacology;Lateral Ventricles/cytology;Neurotransmitters/metabolism;Cell Movement/physiology;Mice;Cell Culture/methods;Cell Differentiation/physiology;Cell Division/drug effects;Astrocytes/cytology}, Number = {2}, Organization = {Institute for Stem Cell Research, Department of Biotechnology, San Raffaele Hospital, 20132 Milan, Italy. gritti.angela\@hsr.it.}, Pages = {437-45}, Title = {Multipotent neural stem cells reside into the rostral extension and olfactory bulb of adult rodents}, Uuid = {16268DDD-46C4-4257-AF20-F95217DD02BF}, Volume = {22}, Year = {2002}, url = {papers/Gritti_JNeurosci2002.pdf}} @article{Gritti:1995, Abstract = {Stem cells isolated from the CNS of both embryonic and adult mice undergo extensive proliferation in the presence of epidermal growth factor (EGF). Removal of EGF determines the differentiation of these cells into neurons and glia. We have recently demonstrated that basic fibroblast growth factor (bFGF) regulates the proliferation of EGF-generated progenitors of the embryonic mouse striatum. We report here that bFGF induces proliferation of some EGF-generated precursors of the adult mouse striatum which, in turn, differentiate in vitro into cells possessing neuron-like morphology and neuronal antigenic properties. These results demonstrate that EGF and bFGF can act sequentially to regulate the de novo generation of neurons from the adult mouse CNS in vitro and suggest the existence of a lineage relationship between EGF- and bFGF-responsive progenitor cells of the adult murine brain. 0304-3940 Journal Article}, Author = {Gritti, A. and Cova, L. and Parati, E. A. and Galli, R. and Vescovi, A. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {Neurosci Lett}, Keywords = {Stem Cells/*physiology;Fibroblast Growth Factor 2/*pharmacology;Epidermal Growth Factor/*physiology;Corpus Striatum;Cell Division;04 Adult neurogenesis factors;Support, Non-U.S. Gov't;Animals;Mice;C abstr;Central Nervous System/physiology}, Number = {3}, Organization = {Laboratory of Cellular Neuropharmacology, National Neurological Institute C. Besta, Milan, Italy.}, Pages = {151-4}, Pubmed = {7753479}, Title = {Basic fibroblast growth factor supports the proliferation of epidermal growth factor-generated neuronal precursor cells of the adult mouse CNS}, Uuid = {F6FDEAC7-42AC-4FE9-B6BE-807A6517D0A5}, Volume = {185}, Year = {1995}, url = {papers/Gritti_NeurosciLett1995.pdf}} @article{Groc:2002, Abstract = {During development, neural activity has been proposed to promote neuronal growth. During the first postnatal week, the hippocampus is characterized by an oscillating neural network activity and a rapid neuronal growth. In the present study we tested in vivo, by injecting tetanus toxin into the hippocampus of P1 rats, whether this neural activity indeed promotes growth of pyramidal cells. We have previously shown that tetanus toxin injection leads to a strong reduction in the frequency of spontaneous GABA and glutamatergic synaptic currents, and to a complete blockade of the early neural network activity during the first postnatal week. Morphology of neurobiotin-filled CA1 pyramidal cells was analyzed at the end of the first postnatal week (P6-10). In activity-reduced neurons, the total length of basal dendritic tree was three times less than control. The number, but not the length, of basal dendritic branches was affected. The growth impairment was restricted to the basal dendrites. The apical dendrite, the axons, or the soma grew normally during activity deprivation. Thus, the in vivo neural activity in the neonate hippocampus seems to promote neuronal growth by initiating novel branches.}, Author = {Groc, Laurent and Petanjek, Zdravko and Gustafsson, Bengt and Ben-Ari, Yehezkel and Hanse, Eric and Khazipov, Roustem}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Dendrites;Research Support, Non-U.S. Gov't;21 Neurophysiology;GABA Modulators;Hippocampus;Pyramidal Cells;Rats;Tetanus Toxin;Rats, Wistar;Neural Inhibition;Animals, Newborn;Synaptic Transmission;gamma-Aminobutyric Acid;Animals;Biotin;24 Pubmed search results 2008;21 Epilepsy}, Medline = {22341348}, Month = {11}, Nlm_Id = {8918110}, Number = {10}, Organization = {Institute of Physiology and Pharmacology, Department of Physiology, G{\"o}teborg University, G{\"o}teborg, Sweden. laurent.groc\@physiol.gu.se}, Pages = {1931-8}, Pii = {2264}, Pubmed = {12453057}, Title = {In vivo blockade of neural activity alters dendritic development of neonatal CA1 pyramidal cells}, Uuid = {FBC9D4E4-9350-4E2C-AF29-34E771B03144}, Volume = {16}, Year = {2002}} @article{Gross:1996, Abstract = {The epigenetic signals that regulate lineage development in the embryonic mammalian brain are poorly understood. Here we demonstrate that a specific subclass of the transforming growth factor beta superfamily, the bone morphogenetic proteins (BMPs), cause the selective, dose-dependent elaboration of the astroglial lineage from murine embryonic subventricular zone (SVZ) multipotent progenitor cells. The astroglial inductive effect is characterized by enhanced morphological complexity and expression of glial fibrillary acidic protein, with concurrent suppression of neuronal and oligodendroglial cell fates. SVZ progenitor cells express transcripts for the appropriate BMP-specific type I and II receptor subunits and selective BMP ligands, suggesting the presence of paracrine or autocrine developmental signaling pathways (or both). These observations suggest that the BMPs have a selective role in determining the cell fate of SVZ multipotent progenitor cells or their more developmentally restricted progeny. 0896-6273 Journal Article}, Author = {Gross, R. E. and Mehler, M. F. and Mabie, P. C. and Zang, Z. and Santschi, L. and Kessler, J. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuron}, Keywords = {Cell Differentiation/drug effects;Signal Transduction;Corpus Striatum/*cytology/embryology;Animals;Cells, Cultured;*Receptors, Growth Factor;Neurons/*cytology;Receptors, Cell Surface/*physiology;Astrocytes/*cytology/drug effects/physiology;Oligodendroglia/drug effects;Kinetics;Mammals;Bone Morphogenetic Proteins/*pharmacology;C abstr;Stem Cells/*cytology/drug effects;Glial Fibrillary Acidic Protein/analysis;Embryo;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Mice;Biological Markers}, Number = {4}, Organization = {Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.}, Pages = {595-606}, Pubmed = {8893018}, Title = {Bone morphogenetic proteins promote astroglial lineage commitment by mammalian subventricular zone progenitor cells}, Uuid = {F67C532E-66B1-49B3-890D-7D5704345015}, Volume = {17}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8893018}} @article{Grossmann:2002, Abstract = {Some parenchymal microglia in mammalian brain tissues, termed "juxtavascular microglia," directly contact the basal lamina of blood vessels; however, the functional consequences of this unique structural relationship are unknown. Here we used a rat brain slice model of traumatic brain injury to investigate the dynamic behavior of juxtavascular microglia following activation. Juxtavascular microglia were identified by confocal 3D reconstruction in tissue slices stained with a fluorescent lectin (FITC-IB4) that labels both microglia and blood vessel endothelial cells. Immunolabeling confirmed that juxtavascular cells were true parenchymal microglia (OX42+, ED2-) and not perivascular cells or pericytes. Time-lapse imaging in live tissue slices revealed that activating juxtavascular microglia withdraw most extant branches but often maintain contact with blood vessels, usually moving to the surface of a vessel within 1-4 h. Subsequently, some microglia migrate along the parenchymal surface of vessels, moving at rates up to 40 microm/h. Activated juxtavascular microglia sometimes repeatedly extend veil-like protrusions into the surrounding tissue, consistent with a role in tissue surveillance. Juxtavascular cells were twice as likely as nonjuxtavascular cells to be locomotory by 10 h in vitro, suggesting an enhanced activation response. Moreover, 38\%of all juxtavascular cells migrated along a vessel, whereas this was never observed for a nonjuxtavascular cell. These observations identify a mobile subpopulation (10\%-30\%) of parenchymal microglia that activate rapidly and are preferentially recruited to the surfaces of blood vessels following brain tissue injury. The dynamic and sustained interaction of microglia with brain microvessels may facilitate signaling between injured brain parenchyma and components of the blood-brain barrier or circulating immune cells of the blood in vivo.}, Author = {Grossmann, Ruth and Stence, Nick and Carr, Jenny and Fuller, Leah and Waite, Marc and Dailey, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Fluorescent Dyes;Microscopy, Video;Research Support, Non-U.S. Gov't;Animals;Aging;Rats;Microscopy, Confocal;Fluorescent Antibody Technique;Brain;Microglia;Immunologic Surveillance;Rats, Sprague-Dawley;Hippocampus;Cell Movement;Not relevant;11 Glia;Time Factors;Organ Culture Techniques;Brain Injuries;Support, Non-U.S. Gov't;Gliosis;Organ Culture;Blood Vessels}, Medline = {21846133}, Month = {3}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA.}, Pages = {229-40}, Pii = {10.1002/glia.10031}, Pubmed = {11857681}, Title = {Juxtavascular microglia migrate along brain microvessels following activation during early postnatal development}, Uuid = {9AE3B6B7-AD70-428B-BDE6-55C4611891AC}, Volume = {37}, Year = {2002}, url = {papers/Grossmann_Glia2002.pdf}} @article{Grove:2002, Abstract = {Gene therapy application to pulmonary airways and alveolar spaces holds tremendous promise for the treatment of lung diseases. However, safe and effective long-term gene expression using viral and nonviral vectors has not yet been achieved. Adenoviral vectors, with a natural affinity for airway epithelia, have been partially effective, but are inflammatory and induce only transient gene expression. We investigate the novel approach of using retrovirally transduced multipotent bone marrow-derived stem cells (BMSC) to deliver gene therapy to lung epithelium. We have shown previously that up to 20\%of lung epithelial cells can be derived from marrow following BMSC transplantation. Here, irradiated female mice were transplanted with male marrow that had been transduced with retrovirus encoding eGFP. Transgene expressing lung epithelial cells were present in all recipients analyzed at 2, 5, or 11 mo after transplant (n = 10), demonstrating that highly plastic BMSC can be stably transduced in vitro and retain their ability to differentiate into lung epithelium while maintaining long-term transgene expression.}, Author = {Grove, Joanna E. and Lutzko, Carolyn and Priller, Josef and Henegariu, Octavian and Theise, Neil D. and Kohn, Donald B. and Krause, Diane S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {1044-1549}, Journal = {Am J Respir Cell Mol Biol}, Keywords = {Respiratory Mucosa;Animals;Protein Precursors;Bone Marrow Transplantation;Lung Diseases;Indicators and Reagents;Proteolipids;Female;Mice, Inbred C57BL;Retroviridae;11 Glia;Green Fluorescent Proteins;Hematopoietic Stem Cell Transplantation;RNA, Messenger;Research Support, U.S. Gov't, P.H.S.;Gene Therapy;Mice;Luminescent Proteins;Gene Expression}, Medline = {22330667}, Month = {12}, Nlm_Id = {8917225}, Number = {6}, Organization = {Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA.}, Pages = {645-51}, Pubmed = {12444022}, Title = {Marrow-derived cells as vehicles for delivery of gene therapy to pulmonary epithelium}, Uuid = {251C0ACD-8FBF-498D-A0E8-246D2D0C1927}, Volume = {27}, Year = {2002}} @article{Grove:1998, Abstract = {In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. The Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryonic development. Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in the cortical hem both before and just as the CPe begins to form, and persists until birth. In addition, although the cortical hem does not show features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant, telencephalic CPe fails to develop. We show that Wnt gene expression is deficient at the cortical hem in XtJ/XtJ mice, but that the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila gene cubitus interruptus (ci), which encodes a transcriptional regulator of the Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.}, Author = {Grove, E. A. and Tole, S. and Limon, J. and Yip, L. and Ragsdale, C. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Fibroblast Growth Factor 8;10 Development;Cell Differentiation;10 Hippocampus;Animals;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Transcription Factors;Proteins;Epithelium;Mutation;Telencephalon;Hippocampus;Wnt2 Protein;Wnt Proteins;Xenopus Proteins;Research Support, U.S. Gov't, P.H.S.;Mesoderm;Cerebral Cortex;Neurons;Choroid Plexus;Morphogenesis;Fibroblast Growth Factors;Mice;Proto-Oncogene Proteins;Nerve Tissue Proteins;Kruppel-Like Transcription Factors;Repressor Proteins;Research Support, Non-U.S. Gov't}, Medline = {98252821}, Month = {6}, Nlm_Id = {8701744}, Number = {12}, Organization = {Department of Pharmacological and Physiological Sciences, University of Chicago, Chicago, IL, USA. egrove\@drugs.bsd.uchicago.edu}, Pages = {2315-25}, Pubmed = {9584130}, Title = {The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice}, Uuid = {F928B2D2-5DD5-4294-92FF-8A9117DCE926}, Volume = {125}, Year = {1998}} @article{Grove:2004, Abstract = {Stem cell plasticity refers to the ability of adult stem cells to acquire mature phenotypes that are different from their tissue of origin. Adult bone marrow cells (BMCs) include two populations of bone marrow stem cells (BMCs): hematopoietic stem cells (HSCs), which give rise to all mature lineages of blood, and mesenchymal stem cells (MSCs), which can differentiate into bone, cartilage, and fat. In this article, we review the literature that lends credibility to the theory that highly plastic BMCs have a role in maintenance and repair of nonhematopoietic tissue. We discuss the possible mechanisms by which this may occur. Also reviewed is the possibility that adult BMCs can change their gene expression profile after fusion with a mature cell, which has brought into question whether this stem cell plasticity is real.}, Author = {Grove, Joanna E. and Bruscia, Emanuela and Krause, Diane S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {Cell Differentiation;Transplantation, Heterologous;Hematopoietic Stem Cells;Bone Marrow Cells;08 Aberrant cell cycle;Stem Cells;22 Stem cells;Humans;Animals;24 Pubmed search results 2008;review;Stem Cell Transplantation}, Nlm_Id = {9304532}, Number = {4}, Organization = {Department of Laboratory Medicine, Yale University School of Medicine, P.O. Box 8035, 333 Cedar Street, New Haven, CT 06520-8035, USA. joanna.grove\@yale.edu}, Pages = {487-500}, Pii = {22/4/487}, Pubmed = {15277695}, Title = {Plasticity of bone marrow-derived stem cells}, Uuid = {A0CE026F-FBF0-47F7-BD9C-137A472EF73B}, Volume = {22}, Year = {2004}, url = {papers/Grove_StemCells2004.pdf}} @article{Groves:2003, Abstract = {Following permanent transection of the adult rat sciatic nerve, sensory neuron apoptosis in the contributing L4 and L5 dorsal root ganglia can be observed for at least 6 months afterwards. To establish the profile of any sensory neuron apoptosis and loss over time when axonal regeneration is allowed, serial sections of L4 and L5 ganglia were examined and the neurons counted using a stereological technique 1, 2 and 3 months after crushing the right sciatic nerve at mid-thigh level. Our results show that an identical degree of sensory neuron loss and apoptosis occurs 1 month after crush as at 1 month after permanent transection. However, at 3 months no neurons undergoing apoptosis could be observed and no significant loss could be detected in the ipsilateral ganglia when compared to unoperated controls. One explanation was a neuronal replacement mechanism, which was investigated by administering bromodeoxyuridine to rats for 1 month after sciatic nerve transection or crush, prior to detection using immunohistochemistry on sections of their ganglia after 2 months. The presence of bromodeoxyuridine in the nuclei of occasional cells that would be counted as neurons on the basis of size and morphology indicates that a process of apparent neurogenesis may underlie the profile of sensory neuron loss after axotomy. 0300-4864 Journal Article}, Author = {Groves, M. J. and Schanzer, A. and Simpson, A. J. and An, S. F. and Kuo, L. T. and Scaravilli, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurocytol}, Keywords = {06 Adult neurogenesis injury induced;D pdf}, Number = {2}, Organization = {Department of Molecular Pathogenesis, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG. m.groves\@ion.ucl.ac.uk}, Pages = {113-22}, Pubmed = {14707546}, Title = {Profile of adult rat sensory neuron loss, apoptosis and replacement after sciatic nerve crush}, Uuid = {D8FDED1D-636C-4B89-B53A-197F01EF7015}, Volume = {32}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14707546}} @article{Grubb:2008, Abstract = {The first synapse in olfaction undergoes considerable anatomical plasticity in both early postnatal development and adult neurogenesis, yet we know very little concerning its functional maturation at these times. Here, we used whole-cell recordings in olfactory bulb slices to describe olfactory nerve inputs to developing postnatal neurons and to maturing adult-born cells labeled with a GFP-encoding lentivirus. In both postnatal development and adult neurogenesis, the maturation of olfactory nerve synapses involved an increase in the relative contribution of AMPA over NMDA receptors, and a decrease in the contribution of NMDA receptors containing the NR2B subunit. These postsynaptic transformations, however, were not mirrored by presynaptic changes: in all cell groups, paired-pulse depression remained constant as olfactory nerve synapses matured. Although maturing cells may therefore offer, transiently, a functionally distinct connection for inputs from the nose, presynaptic function at the first olfactory connection remains remarkably constant in the face of considerable anatomical plasticity.}, Author = {Grubb, Matthew S. and Nissant, Antoine and Murray, Kerren and Lledo, Pierre-Marie M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;Cell Differentiation;research support, non-u.s. gov't;Smell;Female;Neuronal Plasticity;Mice, Inbred C57BL;comparative study;Animals, Newborn;Animals;Male;Mice;Neurons;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8102140}, Number = {11}, Organization = {Perception and Memory Laboratory, Unit{\'e} de Recherche Associ{\'e}e 2182, Centre National de la Recherche Scientifique, Institut Pasteur, F-75724 Paris Cedex 15, France.}, Pages = {2919-32}, Pii = {28/11/2919}, Pubmed = {18337423}, Title = {Functional maturation of the first synapse in olfaction: development and adult neurogenesis}, Uuid = {3072E13E-A7C3-41C3-9E93-9ADDE61476BE}, Volume = {28}, Year = {2008}, url = {papers/Grubb_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5550-07.2008}} @article{Gu:1999, Abstract = {The objective was to determine if projections of single neurons to primary motor cortex preferentially terminate in several efferent zones that could form synergies for the execution of limb movements. Intracortical microstimulation was used to identify zones evoking hip flexion (HF), elbow flexion (EF), and both plantarflexion (PF) and dorsiflexion (DF) about the ankle. Histological examination showed that the zones from which some movements were evoked extended beyond the agranular cortex into granular cortex. Fluorogold, Fast blue, and propridium iodide or rhodamine-labeled dextran were injected into three of these four efferent zones in each rat. There was a virtual absence of multiple-labeled cells despite having an intermingling of different-colored cells of which 15\%in frontal cortex were less than 1.2 mm away from a neighboring neuron that projected to a different efferent zone. This suggests that single neurons projecting to the motor cortex do not hard-wire specific synergies but rather project to single efferent zones in order to offer the greatest degree of freedom for the generation of movements. The distribution of ventral posterolateral and ventrolateral thalamic nucleus labeling depended on whether the injections were in granular or agranular cortex. Conversely, frontal cortex projections to motor efferent zones were made irrespective of their location in either granular or agranular cortex and thereby supporting their presumed role in the control of movements. Hindlimb motor cortex injections yielded retrograde labeling that extended into the more localised distribution of frontal cortex neurons retrogradely labeled from forelimb injections. This may allow hindlimb movements to be synchronized by forelimb movements during walking on challenging terrain.}, Author = {Gu, X. and Staines, W. A. and Fortier, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Electric Stimulation;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Movement;Rats, Sprague-Dawley;Rats;Motor Cortex;Extremities;Electromyography;Neural Pathways;Brain Mapping;Thalamus;Animals;Male;Neurons;Frontal Lobe}, Medline = {99373218}, Month = {7}, Nlm_Id = {0045503}, Number = {2}, Organization = {Department of Cellular and Molecular Medicine, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada.}, Pages = {175-87}, Pii = {S0006899399015760}, Pubmed = {10415372}, Title = {Quantitative analyses of neurons projecting to primary motor cortex zones controlling limb movements in the rat}, Uuid = {22AE4011-F923-4CDC-B483-3A66BEE88244}, Volume = {835}, Year = {1999}} @article{Gu:2000, Abstract = {Neurogenesis occurs throughout life in the dentate gyrus of hippocampus and subventricular zone, but this phenomenon has rarely been observed in other brain regions of adult mammals. The aim of the current study was to investigate the cell proliferation process in the ischemically challenged region-at-risk after focal cerebral ischemia in the adult rat brain. A reversible photothrombotic ring stroke model was used, which features sustained hypoperfusion followed by late spontaneous reperfusion and a remarkable morphologic tissue recovery in the anatomically well defined somatosensory cortical region-at-risk. Twelve-week-old male Wistar rats received repeated intraperitoneal injections of the cell proliferation specific marker 5-bromodeoxyuridine (BrdU) after stroke induction. Immunocytochemistry of coronal brain sections revealed that the majority of BrdU-positive cells were of glial, macrophage, and endothelial origin, whereas 3\%to 6\%of the BrdU-positive cells were double-labeled by BrdU and the neuronspecific marker Map-2 at 7 and 100 days after stroke onset in the region-at-risk. They were distributed randomly in cortical layers II-VI. Three-dimensional confocal analyses of BrdU and the neuronal-specific marker Neu N by double immunofluorescence confirmed their colocalization within the same cells at 72 hours and 30 days after stroke induction. This study suggests that, as a potential pathway for brain repair, new neurons can be generated in the cerebral cortex of adult rats after sublethal focal cerebral ischemia. 0271-678x Journal Article}, Author = {Gu, W. and Brannstrom, T. and Wester, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {J Cereb Blood Flow Metab}, Keywords = {Bromodeoxyuridine/pharmacokinetics;Intracranial Thrombosis/*complications/etiology;Rats;Cerebral Cortex/metabolism/pathology/*physiopathology;Cerebrovascular Accident/*etiology/metabolism/pathology/*physiopathology;Rats, Wistar;Radiation Injuries, Experimental/*complications;D pdf;Animals;Support, Non-U.S. Gov't;Male;*Nerve Regeneration}, Number = {8}, Organization = {Department of Medicine, Umea Stroke Center, University of Umea, Sweden.}, Pages = {1166-73}, Title = {Cortical neurogenesis in adult rats after reversible photothrombotic stroke}, Uuid = {BAA17290-C26D-11DA-969D-000D9346EC2A}, Volume = {20}, Year = {2000}, url = {papers/Gu_JCerebBloodFlowMetab2000.pdf}} @article{Guadano-Ferraz:1990, Abstract = {In the corpus callosum of the cat, the heavy subunit of neurofilaments (NFH) can be demonstrated with the monoclonal antibody NE14, as early as P11, not at P3, and only in a few axons. At P18-19 and more markedly at P29, many more callosal axons have become positive to NE14 and this is similar to what is found in the adult. In contrast, callosal axons become positive to the neurofilament antibody SMI-32 only between P29 and P39 and remain positive in the adult. Treatment with alkaline phosphatase prevents axonal staining with NE14, but results in SMI-32 staining of a few callosal axons as early as P11, but not at P3. Between P11 and P19 the number of axons stained with SMI-32 after alkaline phosphatase treatment increases, in parallel with that of axons stained with NE14. Thus NE14 appears to recognize a phosphorylated form of NFH, while SMI-32 appears to recognize an epitope of NFH which is either masked by phosphate or inaccessible until between P29 and P39, unless the tissue is treated with alkaline phosphatase. These two forms of NFH appear towards the end of the period of massive developmental elimination of callosal axons. They are also synchronous with changes in the spacing of neurofilaments quantified in a separate ultrastructural study. These cytoskeletal changes may terminate the juvenile-labile state of callosal axons and allow further axial growth of the axon.}, Author = {Guadano-Ferraz, A. and Riederer, B. M. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Embryo;Aging;Corpus Callosum;Cats;Neurofilament Proteins;Not relevant;11 Glia;Animals, Newborn;Alkaline Phosphatase;Animals;Support, Non-U.S. Gov't;Intermediate Filament Proteins;Macromolecular Systems;Axons}, Medline = {91084996}, Month = {11}, Nlm_Id = {8908639}, Number = {2}, Organization = {Institute of Anatomy, University of Lausanne, Switzerland.}, Pages = {244-56}, Pubmed = {2124524}, Title = {Developmental changes in the heavy subunit of neurofilaments in the corpus callosum of the cat}, Uuid = {6C0482ED-114F-41AB-A0DA-4B29282B2723}, Volume = {56}, Year = {1990}} @article{Guadano-Ferraz:1994, Abstract = {The development of axon number in the anterior commissure (AC) was analyzed in 39 normal and 37 hypothyroid rats using conventional electron microscopy. Hypothyroid rats underwent antithyroid treatment with methimazole from embryonic day (E) 14 onwards, followed in a fraction of the animals by thyroidectomy at postnatal day (P) 6. In normal rats, the midsagittal cross-sectional anterior commissure area (ACA) increased throughout their life; in hypothyroid rats, ACA was stationary from P4 onwards and at P174-180 it was reduced by 39\%relative to normal rats. In normal rats, the number of AC axons increased rapidly from 168,500 at E18 to, on average, 1,049,000 from P4 onwards. Similarly, in hypothyroid rats, the number of axons increased from 135,000 at E18 to, on average, 1,052,000 from P4 onwards. At all ages, the number of axons was similar in normal and hypothyroid rats. During development of the AC, the evolution of axon number observed in normal and hypothyroid rats is different from what was reported for other telencephalic commissures, including the AC of the monkey, where an important fraction of the axons are eliminated postnatally. Antithyroid treatment dissociated ACA from total number of AC axons.}, Author = {Guada\~{n}o Ferraz, A. and Escobar del Rey, F. and Morreale de Escobar, G. and Innocenti, G. M. and Berbel, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Reference Values;Hypothyroidism;Rats;Not relevant;Rats, Wistar;11 Glia;Support, Non-U.S. Gov't;Male;Brain;Animals}, Medline = {95112383}, Month = {9}, Nlm_Id = {8908639}, Number = {2}, Organization = {Departament d'Histologia, Facultat de Medicina, Universitat d'Alacant, Spain.}, Pages = {293-308}, Pubmed = {7813049}, Title = {The development of the anterior commissure in normal and hypothyroid rats}, Uuid = {1CE34B0D-0D77-4694-A09D-B47E54284C40}, Volume = {81}, Year = {1994}} @article{Guandalini:1998, Abstract = {This study investigated in the rat the corticocortical projections of the frontal eye field (FEF), which is located within the medial frontal cortex. The experiments were carried out on Wistar rats. Seven animals received a single iontophoretic injection of Phaseolus vulgaris leucoagglutinin in an FEF site within the medial frontal cortex where intracortical microstimulation elicited eye movements. In these cases, anterogradely labeled fibers and terminal-like elements were found in both hemispheres. The densest labeling was seen in the injected hemisphere, where labeled fibers prevailed in the visual cortex and their laminar distribution differed between the primary and secondary visual cortices. Dense labeled fibers were also seen in the frontal and retrosplenial cortex, whereas a columnar arrangement of terminal-like elements was detected in a restricted part of area 1 of the somatosensory cortex. Contralaterally to the injection site, labeled fibers were distributed mainly in the homotopic region. In two animals, the tracer was injected in a site at the FEF border whose stimulation evoked eye and whisker movements. In these animals, a different distribution of labeling was observed with respect to the other rats in which the tracer was deposited within the FEF, and anterograde labeling was observed in areas 1 and 2 of the parietal cortex of both hemispheres; in addition, no labeling was observed in these cases in the primary visual cortex. These findings suggest that cortical sites confined within the rat FEF are implicated in the control of orienting and exploring behaviors in addition to the control of eye movement.}, Author = {Guandalini, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0361-9230}, Journal = {Brain Res Bull}, Keywords = {Research Support, Non-U.S. Gov't;Iontophoresis;Rats;Eye Movements;Neural Pathways;Rats, Wistar;Phytohemagglutinins;Male;Animals;Cerebral Cortex;24 Pubmed search results 2008;Frontal Lobe}, Medline = {99101905}, Month = {11}, Nlm_Id = {7605818}, Number = {4}, Organization = {Dipartimento di Scienze Biomediche e Terapie Avanzate, Universit\`{a} di Ferrara, Italy. gnp\@dns.unife.it}, Pages = {377-85}, Pii = {S0361923098001221}, Pubmed = {9886790}, Title = {The corticocortical projections of the physiologically defined eye field in the rat medial frontal cortex}, Uuid = {F4552008-091B-45D2-9035-528F2608352B}, Volume = {47}, Year = {1998}} @article{Guegan:1998, Abstract = {After an ischemic episode induced by the electrocoagulation of the left middle cerebral artery (MCA) in mouse, neurons within the damaged territory die either by an apoptotic or by a necrotic process. Most of the cortical neurons within the ischemic area display both morphological and biochemical signs of programmed cell death: nuclear condensation, DNA degradation, formation of apoptotic bodies, and glutathione depletion. In fact, apoptosis essentially contributes to the expansion of the ischemic lesion and the maximum of damaged territory is reached 24 h postocclusion. Several potentially neuroprotective pathways have been evidenced in different experimental models of ischemia including the activation of antioxidant enzyme activities and/or the recruitment of neurotrophic as well as antiapoptotic factors. In our model of permanent focal ischemia induced by MCA occlusion, we measured the temporal synthesis of nerve growth factor (NGF) and examined the status of antioxidant enzymes as well as Bcl-2 antiapoptotic product. We detected in both cortices a transient increase of NGF which peaks at 6 h. Moreover, we reported that glutathione peroxidase is recruited with a time course which parallels NGF synthesis. Finally, we observed the induction of Bcl-2 in safe neurons; this may represent a self-protective response against ischemia- induced apoptosis. We provide evidence that in a model of permanent focal ischemia, several neuroprotective pathways could be coactivated.}, Author = {Guegan, C. and Ceballos-Picot, I. and Nicole, A. and Kato, H. and Onteniente, B. and Sola, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Exp Neurol}, Keywords = {Neurons/*cytology/*enzymology;Enzyme Activation/physiology;Neuroprotective Agents/*metabolism;Apoptosis/*physiology;Cerebral Cortex/cytology/pathology;Animal;Neuroglia/chemistry;Glial Fibrillary Acidic Protein/analysis;Cerebral Infarction/metabolism;Mice, Inbred C57BL;Brain Chemistry/physiology;Cell Survival/physiology;Male;Antioxidants/metabolism;Support, Non-U.S. Gov't;Superoxide Dismutase/analysis/metabolism;Mice, Inbred DBA;06 Adult neurogenesis injury induced;Proto-Oncogene Proteins c-bcl-2/analysis/metabolism;D;Mice;Brain Ischemia/*metabolism;Nerve Growth Factors/biosynthesis/metabolism;Immunohistochemistry;Necrosis;Glutathione/metabolism}, Number = {2}, Organization = {Laboratoire de Neurosciences, Universite de Caen, CNRS UMR 6551, Caen, 14074, France.}, Pages = {371-80.}, Title = {Recruitment of several neuroprotective pathways after permanent focal ischemia in mice}, Uuid = {5FE21A2A-22D2-47CF-8354-C2EFED961004}, Volume = {154}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9878175}} @article{Guerrier:2007, Abstract = {The nuclei of dividing neural progenitors undergo a cell-cycle-dependent change in position along the apico-basal axis known as interkinetic nuclear migration (INM). The functional relationship between INM and the mode of division of neural progenitors remains elusive, in part because its regulation at the molecular level is poorly understood. In this issue of Neuron, Xie et al. identify two centrosomal proteins (Cep120 and TACCs) regulating the INM of cortical neural progenitors.}, Author = {Guerrier, Sabrice and Polleux, Franck}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {comment;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Neuroscience Center, Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7250, USA.}, Pages = {1-3}, Pii = {S0896-6273(07)00717-9}, Pubmed = {17920006}, Title = {The ups and downs of neural progenitors: Cep120 and TACCs control interkinetic nuclear migration}, Uuid = {6555BD0E-F9A5-47A6-AA78-8D6C80325D2B}, Volume = {56}, Year = {2007}, url = {papers/Guerrier_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.09.019}} @article{Guerrini:1999, Author = {Guerrini, R. and Andermann, E. and Avoli, M. and Dobyns, W. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0091-3952}, Journal = {Adv Neurol}, Keywords = {Epilepsy;10 Development;research support, non-u.s. gov't;10 genetics malformation;Congenital Abnormalities;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Nlm_Id = {0367524}, Organization = {Department of Child Neurology and Psychiatry, University of Pisa, Italy.}, Pages = {95-121}, Pubmed = {10514808}, Title = {Cortical dysplasias, genetics, and epileptogenesis}, Uuid = {0DF9D7D7-8F79-4F63-83B9-9A5D7091B7DF}, Volume = {79}, Year = {1999}} @article{Guerrini:2001, Abstract = {Malformations of the cerebral cortex are an important cause of developmental disabilities and epilepsy. Here we review those malformations for which a genetic basis has been elucidated or is suspected and the types of associated epilepsy. Schizencephaly (cleft brain) has a wide anatomo-clinical spectrum, including partial epilepsy in most patients. Familial occurrence is rare. Heterozygous mutations in the EMX2 gene were reported in 13 patients. X-linked bilateral periventricular nodular heterotopia (BPNH) consists of typical BPNH with epilepsy in females and prenatal lethality in males. About 88\%of patients have partial epilepsy. Filamin A mutations, all leading to a truncated protein, have been reported in three families and in sporadic patients. The most frequent forms of lissencephaly (agyria-pachygyria) are caused by mutations of LIS1. XLIS mutations cause classical lissencephaly in hemizygous males and subcortical band heterotopia (SBH) in heterozygous females. The thickness of the heterotopic band and the degree of pachygyria correlate with the likelihood of developing Lennox-Gastaut syndrome. Mutations of the coding region of XLIS were found in all reported pedigrees and in 38-91\%of sporadic female patients with SBH. With few exceptions, children with LIS1 mutations have isolated lissencephaly, with severe developmental delay and infantile spasms. Autosomal recessive lissencephaly with cerebellar hypoplasia, accompanied by severe developmental delay, seizures, and hypotonia has been associated with mutations of the reelin gene. Fukuyama congenital muscular dystrophy is due to mutations of the fukutin gene and is accompanied by polymicrogyria. Febrile seizures and epilepsy with generalized tonic-convulsions appear in about 50\%of children but are usually not severe. Tuberous sclerosis (TS) is caused by mutations in at least two genes, TSC1 and TSC2; 75\%of cases are sporadic; 60\%of patients have epilepsy, manifested in 50\%of them as infantile spasms. TSC1 mutations seem to cause a milder disease with fewer cortical tubers and lower frequency of seizures. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria had familial occurrence on several occasions. Genetic heterogeneity is likely, including autosomal recessive, X-linked dominant, X-linked recessive inheritance, and association with 22q11.2 deletions. About 65\%of patients have severe epilepsy, often Lennox-Gastaut syndrome.}, Author = {Guerrini, R. and Carrozzo, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0148-7299}, Journal = {Am J Med Genet}, Keywords = {Epilepsy;Chromosome Mapping;Microfilament Proteins;Tuberous Sclerosis;24 Pubmed search results 2008;21 Neurophysiology;Point Mutation;21 Epilepsy;Contractile Proteins;Muscular Dystrophies;Humans;Microtubule-Associated Proteins;Cerebral Cortex;review;Cell Movement}, Medline = {21462259}, Nlm_Id = {7708900}, Number = {2}, Organization = {Pediatric Neurology, Institute of CHild Health and Great Ormond Street Hospital for Children, University College of London, UK. R.Guerrini\@ich.ucl.ac.uk}, Pages = {160-73}, Pii = {10.1002/ajmg.1569}, Pubmed = {11579436}, Title = {Epilepsy and genetic malformations of the cerebral cortex}, Uuid = {E2205C53-D232-463A-8333-615FB3EECC17}, Volume = {106}, Year = {2001}, url = {papers/Guerrini_AmJMedGenet2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ajmg.1569}} @article{Guerrini:2005, Abstract = {We reviewed the epileptogenic cortical malformations for which a causative gene has been cloned or a linkage obtained. X-linked bilateral periventricular nodular heterotopia (BPNH) consists of typical BPNH with epilepsy in female patients and prenatal lethality in most males. About 90\%of patients have focal epilepsy. Filamin A mutations have been reported in all families and in approximately 20\%of sporadic patients. A rare recessive form of BPNH also has been reported. Most cases of lissencephaly-pachygyria are caused by mutations of LIS1 and XLIS genes. LIS1 mutations cause a more severe malformation posteriorly. Most children have isolated lissencephaly, with severe developmental delay and infantile spasms, but milder phenotypes have been recorded. XLIS usually causes anteriorly predominant lissencephaly in male patients and subcortical band heterotopia (SBH) in female patients. Thickness of the band and severity of pachygyria correlate with the likelihood of developing Lennox-Gastaut syndrome. Mutations of the coding region of XLIS are found in all reported pedigrees and in 50\%of sporadic female patients with SBH. Autosomal recessive lissencephaly with cerebellar hypoplasia; accompanied by severe delay, hypotonia, and seizures, has been associated with mutations of the RELN gene. Schizencephaly has a wide anatomoclinical spectrum, including focal epilepsy in most patients. Familial occurrence is rare. Initial reports of heterozygous mutations in the EMX2 gene need confirmation. Among several syndromes featuring polymicrogyria, bilateral perisylvian polymicrogyria shows genetic heterogeneity, including linkage to Xq28 in some pedigrees, autosomal recessive inheritance in others, and association with 22q11.2 deletion in some patients. About 65\%of patients have severe epilepsy, often Lennox-Gastaut syndrome. Recessive bilateral frontal polymicrogyria has been linked to chromosome 16q12.2-21.}, Author = {Guerrini, Renzo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Magnetic Resonance Imaging;Genetic Screening;Child, Preschool;Humans;Age of Onset;Tuberous Sclerosis;review;Brain;Female;Epilepsy;Infant;Child;21 Epilepsy;Terminology;Male;Linkage (Genetics);Nervous System Malformations;Cerebral Cortex;21 Neurophysiology;Genetic Counseling;Cerebellum;Infant, Newborn;24 Pubmed search results 2008;Adolescent}, Nlm_Id = {2983306R}, Organization = {Epilepsy, Neurophysiology and Neurogenetics Unit, Division of Child Neurology and Psychiatry, University of Pisa and Research Institute Stella Maris Foundation, Pisa, Italy. renzo.guerrini\@inpe.unipi.it}, Pages = {32-7}, Pii = {EPI461010}, Pubmed = {15816977}, Title = {Genetic malformations of the cerebral cortex and epilepsy}, Uuid = {4B628DCD-8466-46C6-ACEB-C74ADDF00C63}, Volume = {46 Suppl 1}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.0013-9580.2005.461010.x}} @article{Guerrini:2003, Abstract = {Malformations of the cerebral cortex (MCC) are often associated with severe epilepsy and developmental delay. About 40\%of drug-resistant epilepsies are caused by MCC. Classification of MCC is based on embryological brain development, recognising forms that result from faulty neuronal proliferation, neuronal migration and cortical organisation. Hemimegalencephaly, an enlarged dysplastic hemisphere, can present as early onset severe epileptic encephalopathy or as partial epilepsy. In focal cortical dysplasia (FCD), MRI shows focal cortical thickening and simplified gyration. Patients have drug-resistant, often early onset epilepsy. Complete surgical ablation of FCD is accompanied by remission in up to 90\%of patients, but may be technically difficult. Tuberous sclerosis (TS) is a multisystemic disorder primarily involving the nervous system; 60\%of patients having epilepsy, with 50\%having infantile spasms. TS is caused by mutations in the TSC1 and TSC2 genes; 75\%of cases are sporadic. TSC1 mutations cause a milder disease. Bilateral periventricular nodular heterotopia (BPNH) consists of confluent and symmetric nodules of grey matter along the lateral ventricles. X-linked BPNH presents with epilepsy in females and prenatal lethality in most males. Most patients have partial epilepsy. Filamin A mutations have been reported in families and sporadic patients. Lissencephaly (LIS smooth brain) is a severe MCC characterised by absent or decreased convolutions. Classical LIS is quite rare and manifests with severe developmental delay, spastic quadriparesis and severe epilepsy. XLIS mutations cause classical lissencephaly in hemizygous males and subcortical band heterotopia in heterozygous females. Thickness of heterotopic band and degree of pachygyria correlate well with phenotype severity. Schizencephaly (cleft brain) has a wide anatomo-clinical spectrum, including partial epilepsy in most patients. Polymicrogyria (excessive number of small and prominent convolutions) has a wide spectrum of clinical manifestations ranging from early onset epileptic encephalopathy to selective impairment of cognitive functions. Bilateral perisylvian polymicrogyria may be familial. Patients present with faciopharingo-glosso-masticatory diplegia and epilepsy, which is severe in about 65\%of patients.}, Author = {Guerrini, Renzo and Sicca, Federico and Parmeggiani, Lucio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {1294-9361}, Journal = {Epileptic Disord}, Keywords = {Epilepsy;21 Epilepsy;Electroencephalography;Brain Diseases;Magnetic Resonance Imaging;21 Neurophysiology;Abnormalities, Multiple;Gene Expression;Humans;Cell Movement;Cerebral Cortex;review;24 Pubmed search results 2008}, Medline = {22982191}, Month = {9}, Nlm_Id = {100891853}, Organization = {Institute of Child Neurology and Psychiatry, University of Pisa, Calambrone, Italy. Renzo.Guerrini\@inpe.unipi.it}, Pages = {S9-26}, Pubmed = {14617417}, Title = {Epilepsy and malformations of the cerebral cortex}, Uuid = {A644E46B-7A6B-4A20-BBFD-D7E3367A47D9}, Volume = {5 Suppl 2}, Year = {2003}} @article{Guerrini:2008, Abstract = {Genetic studies have identified several of the genes associated with malformations of cortical development which might disrupt each of the main stages of cell proliferation and specification, neuronal migration and late cortical organization. The largest malformation groups, focal cortical dysplasia, heterotopia and polymicrogyria, express different perturbations of these stages and carry a variable propensity for lacking activation, preservation or reorganization of cortical function and for atypical cortical organization. Some patients have obvious neurological impairment, whereas others show unexpected deficits that are detectable only by screening. Drug-resistant epilepsy is frequent but might be amenable to surgical treatment. However, the epileptogenic zone might include remote cortical and subcortical regions. Completeness of resection, a key factor for successful surgery, might be difficult, especially in proximity to eloquent cortex. Surgical planning should be based on assessments of structural imaging and of the major functions relevant to the area in question in any such patient.}, Author = {Guerrini, Renzo and Dobyns, William B. and Barkovich, A. James}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {10 Development;10 genetics malformation;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7808616}, Number = {3}, Organization = {Department of Neurology and Neurosurgery, Children's Hospital A. Meyer, University of Florence, Viale Pieraccini 24, 50139, Florence, Italy.}, Pages = {154-62}, Pii = {S0166-2236(08)00037-4}, Pubmed = {18262290}, Title = {Abnormal development of the human cerebral cortex: genetics, functional consequences and treatment options}, Uuid = {B5C821A7-7ED3-41E4-9E61-34AD67ECDC07}, Volume = {31}, Year = {2008}, url = {papers/Guerrini_TrendsNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2007.12.004}} @article{Gueneau:1982, Abstract = {Cell genesis in the subgranular zone of the dentate gyrus of 2-month-old rabbits has been investigated. After incorporation of tritiated thymidine, electron microscopic autoradiography allowed description of the ultrastructure of the cells labelled and the progressive transformation of these cells into granular neurons to be followed. Quantitative evaluation of the time course of this transformation has been performed by light microscope autoradiography using 1-micrometer sections. Precursor cells, labelled initially with 3H-thymidine, were transformed after 5 days into early neuroblasts, these cells in turn giving rise to neurons some 8 days later. At the latest time period examined (42 days), 80\%of the labelled cells were neurons; more than 10\%remained as precursor cells. It is suspected that the latter may behave as reserve cells. Small numbers of glial cells, astrocytes, and microglia, scattered throughout the hilus of the dentate gyrus and the molecular layer, were found labelled, and it is possible that they arise from a different precusor pool. It is concluded that the subgranular zone functions as a secondary matrix for granule neurons of the dentate gyrus in young rabbits. These late-forming and apparently synaptically uncommitted neurons may be recruited during the development and refinement of postnatal behavioral substrates, by one or other of the dominant afferent systems.}, Author = {Gu{\'e}neau, G. and Privat, A. and Drouet, J. and Court, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Thymidine;Cell Differentiation;10 Development;Research Support, Non-U.S. Gov't;Hippocampus;10 Hippocampus;Autoradiography;Microscopy, Electron;Cell Count;Rabbits;Mitosis;Animals;Cytoplasmic Granules;Neurons}, Medline = {83052931}, Nlm_Id = {7809375}, Number = {4}, Pages = {345-58}, Pubmed = {7140583}, Title = {Subgranular zone of the dentate gyrus of young rabbits as a secondary matrix. A high-resolution autoradiographic study}, Uuid = {5E8639BC-698C-11DA-A4B6-000D9346EC2A}, Volume = {5}, Year = {1982}} @article{Guillemin:2004, Abstract = {The phenotypic differentiation of systemic macrophages that have infiltrated the central nervous system, pericytes, perivascular macrophages, and the "real" resident microglial cells is a major immunocytochemical and immunohistochemical concern for all users of cultures of brain cells and brain sections. It is not only important in assessing the purity of cell cultures; it is also of fundamental importance in the assessment of the pathogenetic significance of perivascular inflammatory phenomena within the brain. The lack of a single membranous and/or biochemical marker allowing conclusive identification of these cells is still a major problem in neurobiology. This review briefly discusses the functions of these cells and catalogs a large number of membranous and biochemical markers, which can assist in the identification of these cells.}, Author = {Guillemin, Gilles J. and Brew, Bruce J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0741-5400}, Journal = {J Leukoc Biol}, Keywords = {Pericytes;Research Support, Non-U.S. Gov't;Immunophenotyping;Biological Markers;11 Glia;Microglia;review, tutorial;Macrophages;Humans;Brain;review}, Month = {3}, Nlm_Id = {8405628}, Number = {3}, Organization = {Centre for Immunology, Neuroimmunology Department, St. Vincent's Hospital, Sydney, NSW, Australia. G.Guillemin\@cfi.unsw.edu.au}, Pages = {388-97}, Pii = {jlb.0303114}, Pubmed = {14612429}, Title = {Microglia, macrophages, perivascular macrophages, and pericytes: a review of function and identification}, Uuid = {ACCD6844-43CB-4C65-8F7B-0D74FA12467F}, Volume = {75}, Year = {2004}, url = {papers/Guillemin_JLeukocBiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1189/jlb.0303114}} @article{Guimera:2006, Author = {Guimer\`{a}, Roger and Sales-Pardo, Marta}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1744-4292}, Journal = {Mol Syst Biol}, Keywords = {20 Networks;Metabolism;Evolution;Proteins;24 Pubmed search results 2008;news}, Nlm_Id = {101235389}, Pages = {42}, Pii = {msb4100082}, Pubmed = {16883355}, Title = {Form follows function: the architecture of complex networks}, Uuid = {43D35539-0B3E-4E81-B5BB-91293055E7A4}, Volume = {2}, Year = {2006}, url = {papers/Guimera_MolSystBiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/msb4100082}} @article{Gulyas-Kovacs:2002, Abstract = {Rat neocortical slices express spontaneous epileptiform activity after incubation with GABA(A) receptor blocker bicuculline (BIC, 20 microM), with potassium channel blocker 4-aminopyridine (4-AP, 50 microM) or in Mg(2+)-free medium (LMG). Various parameters of spontaneous and evoked epileptiform discharges and their pharmacological sensitivity were analysed using extracellular field potential recordings in this comparative in vitro study. All types of convulsant solution induced spontaneous epileptiform activity, however, the analysed parameters showed that characteristics of epileptiform discharges are rather different in the three models. The longest duration of discharges was recorded in LMG, while the highest frequency of spontaneous events was detected in 4-AP. The epileptiform field responses elicited by electrical stimulation appeared in an all-or-none manner in BIC. On the contrary, in 4-AP and in LMG the amplitude of the responses increased gradually with increasing stimulation intensities. The NMDA receptor antagonist D,L-2-amino-5-phosphonovaleric acid (APV, 25 microM) abolished the LMG induced spontaneous epileptiform activity and significantly reduced the frequency of the epileptiform discharges in BIC and 4-AP. Blocking the AMPA type of glutamate transmission with 1-(aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466, 40 microM) rapidly abolished BIC-induced spontaneous epileptiform activity and caused a significant decrease in the frequency of 4-AP induced spontaneous epileptiform discharges. However, it had only a weak effect on the LMG-induced epileptiform activity. We conclude that the contribution of NMDA and AMPA types of glutamate receptors to the development and maintenance of epileptiform activity in cortical cell assemblies is different in the three models. There are significant alterations in contribution of NMDA and AMPA types of glutamate receptors to the above-mentioned processes in the different convulsants. In BIC the synchronisation is mainly due to the altered network properties, namely inhibition is reduced in the local circuits. Although inhibition is reduced in the local circuits, the AMPA receptor antagonist relatively easily blocked the synchronised excitation. In 4-AP, and especially in LMG, changes in the membrane characteristics of neurones play a crucial role in the increased excitability. In this case the AMPA antagonist was less effective.}, Author = {Guly{\'a}s-Kov{\'a}cs, A. and D{\'o}czi, J. and Tarnawa, I. and D{\'e}t{\'a}ri, L. and Banczerowski-Pelyhe, I. and Vil{\'a}gi, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Excitatory Amino Acid Antagonists;Anti-Anxiety Agents;Electric Stimulation;Electrophysiology;Animals;Rats;Comparative Study;21 Epilepsy;Female;Epilepsy;Rats, Sprague-Dawley;2-Amino-5-phosphonovalerate;Receptors, AMPA;Male;Bicuculline;Magnesium Deficiency;Potassium Channel Blockers;21 Neurophysiology;Somatosensory Cortex;Convulsants;24 Pubmed search results 2008;4-Aminopyridine;Receptors, N-Methyl-D-Aspartate;Benzodiazepines;Research Support, Non-U.S. Gov't}, Medline = {22122543}, Month = {8}, Nlm_Id = {0045503}, Number = {2}, Organization = {Department of Physiology and Neurobiology, E{\"o}tv{\"o}s Lor{\'a}nd University, P{\'a}zm{\'a}ny P{\'e}ter s{\'e}t{\'a}ny 1/C, 1117 Budapest, Hungary.}, Pages = {174-80}, Pii = {S0006899302027518}, Pubmed = {12126879}, Title = {Comparison of spontaneous and evoked epileptiform activity in three in vitro epilepsy models}, Uuid = {65CD5FDF-F46F-4B89-BDF3-FB15EDA94328}, Volume = {945}, Year = {2002}} @article{Guo:2001, Abstract = {In the present study expression of estrogen receptor subtype -alpha (ERalpha) and -beta (ERbeta) in the cerebral cortex, cerebellum, and olfactory bulb was investigated and compared between neonatal (1 to approximately 3-days-old) and adult (250 to approximately 350 g) rats, using reverse transcription-polymerase chain reaction (RT-PCR). No ERalpha transcripts were detectable in the adult cerebellum and olfactory bulb, whereas very weak expression of ERalpha was present in the adult cerebral cortex. No significant difference in ERbeta transcripts was detectable between the neonatal and adult rats. While transcripts for both ER subtypes were co-expressed in these brain areas of neonatal rats, although ERalpha expression was significantly weaker than ERbeta. Even in the cerebral cortex known to contain both ER subtypes in adult rats, ERalpha transcripts in neonatal rats were much higher than in adult. These observations provide evidence for the existence of different expression patterns of ERalpha/ERbeta transcripts in these three brain areas between the neonatal and adult rats, suggesting that each ER subtype may play a distinct role in the regulation of differentiation, development, and functions of the brain by estrogen.}, Author = {Guo, X. Z. and Su, J. D. and Sun, Q. W. and Jiao, B. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Cell Res}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {4}, Organization = {Department of Biochemistry and Molecular Biology, Second Military Medical University, Shanghai, China. gxzhb\@online.sh.cn}, Pages = {321-4.}, Title = {Expression of estrogen receptor (ER) -alpha and -beta transcripts in the neonatal and adult rat cerebral cortex, cerebellum, and olfactory bulb}, Uuid = {4E5203B2-A9FA-4F44-92C8-4287E6E5F1F2}, Volume = {11}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11787778}} @article{Guo:1996, Abstract = {During development of the Drosophila peripheral nervous system, a sensory organ precursor (SOP) cell undergoes rounds of asymmetric divisions to generate four distinct cells of a sensory organ. Numb, a membrane-associated protein, is asymmetrically segregated into one daughter cell during SOP division and acts as an inherited determinant of cell fate. Here, we show that Notch, a transmembrane receptor mediated cell-cell communication, functions as a binary switch in cell fate specification during asymmetric divisions of the SOP and its daughter cells in embryogenesis. Moreover, numb negatively regulates Notch, probably through direct protein-protein interaction that requires the phosphotyrosine-binding (PTB) domain of Numb and either the RAM23 region or the very C-terminal end of Notch. Notch then positively regulates a transcription factor encoded by tramtrack (ttk). This leads to Ttk expression in the daughter cell that does not inherit Numb. Thus, the inherited determinant Numb bestows a bias in the machinery for cell-cell communication to allow the specification of distinct daughter cell fates. 0896-6273 Journal Article}, Author = {Guo, M. and Jan, L. Y. and Jan, Y. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuron}, Keywords = {Stem Cells/*cytology;Embryo and Fetal Development;Cell Differentiation;10 Development;Membrane Proteins/*physiology;Female;Cell Line;Sense Organs/*cytology;Juvenile Hormones/*physiology;Transcription Factors/physiology;F;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;Male;Drosophila/embryology}, Number = {1}, Organization = {Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.}, Pages = {27-41}, Pubmed = {8755476}, Title = {Control of daughter cell fates during asymmetric division: interaction of Numb and Notch}, Uuid = {1EC00A62-0F3A-4931-9E95-CCAFBA9B7C19}, Volume = {17}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8755476}} @article{Gupta:2003, Abstract = {Several genes essential for neocortical layering have been identified in recent years, but their precise roles in this process remain to be elucidated. Mice deficient in p35--an activator of cyclin-dependent kinase 5 (Cdk5)--are characterized by a neocortex that has inverted layering. To decipher the physiological mechanisms that underlie this defect, we compared time-lapse recordings between p35(-/-) and wild-type cortical slices. In the p35(-/-) neocortex, the classic modes of radial migration--somal translocation and locomotion--were largely replaced by a distinct mode of migration: branched migration. Branched migration is cell-autonomous, associated with impaired neuronal-glial interaction and rare in neurons of scrambler mice, which are deficient in Dab1. Hence, our findings suggest that inside-out layering requires distinct functions of Reelin and p35/Cdk5 signaling, with the latter being important for proper glia-guided migration.}, Author = {Gupta, Amitabh and Sanada, Kamon and Miyamoto, David T. and Rovelstad, Susan and Nadarajah, Bagirathy and Pearlman, Alan L. and Brunstrom, Jan and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {10 Development;research support, non-u.s. gov't;Mice, Knockout;Neuroglia;Female;Nerve Tissue Proteins;in vitro;10 genetics malformation;comparative study;Pregnancy;research support, u.s. gov't, p.h.s.;Animals;Cell Movement;Mice;Neurons;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9809671}, Number = {12}, Organization = {Department of Pathology, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts 02115, USA.}, Pages = {1284-91}, Pii = {nn1151}, Pubmed = {14608361}, Title = {Layering defect in p35 deficiency is linked to improper neuronal-glial interaction in radial migration}, Uuid = {A24FB364-379F-482D-BEE0-C069DC3D5708}, Volume = {6}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1151}} @article{Gupta:2002, Abstract = {Although the basic principles of neocortical development have been known for quite some time, it is only recently that our understanding of the molecular mechanisms that are involved has improved. Such understanding has been facilitated by genetic approaches that have identified key proteins involved in neocortical development, which have been placed into signalling pathways by molecular and cell-biological studies. The challenge of current research is to understand the manner in which these various signalling pathways are interconnected to gain a more comprehensive picture of the molecular intricacies that govern neocortical development. 1471-0056 Journal Article Review Review, Tutorial}, Author = {Gupta, A. and Tsai, L. H. and Wynshaw-Boris, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:48 -0400}, Journal = {Nat Rev Genet}, Keywords = {Signal Transduction/*genetics/physiology;Extracellular Matrix Proteins/physiology;10 Development;Mice, Mutant Strains/physiology;Dynein ATPase/physiology;F both;Microtubule-Associated Proteins/genetics/physiology;Neocortex/*embryology/*physiology;Neuropeptides/genetics/physiology;Neurons/physiology;Animals;Mice;Cell Adhesion Molecules, Neuronal/physiology;Cyclin-Dependent Kinases/physiology;Cell Movement/*genetics/physiology}, Number = {5}, Organization = {Department of Pathology, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, Massachusetts 02115, USA. amitabh-gupta\@student.hms.harvard.edu}, Pages = {342-55}, Title = {Life is a journey: a genetic look at neocortical development}, Uuid = {EF1B178D-36A9-4B30-B031-F9E3BFF501A6}, Volume = {3}, Year = {2002}, url = {papers/Gupta_NatRevGenet2002.pdf}} @article{Gupta:2000, Abstract = {A puzzling feature of the neocortex is the rich array of inhibitory interneurons. Multiple neuron recordings revealed numerous electrophysiological-anatomical subclasses of neocortical gamma-aminobutyric acid-ergic (GABAergic) interneurons and three types of GABAergic synapses. The type of synapse used by each interneuron to influence its neighbors follows three functional organizing principles. These principles suggest that inhibitory synapses could shape the impact of different interneurons according to their specific spatiotemporal patterns of activity and that GABAergic interneuron and synapse diversity may enable combinatorial inhibitory effects in the neocortex.}, Author = {Gupta, A. and Wang, Y. and Markram, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {gamma-Aminobutyric Acid;Animals;Synapses;In Vitro;Rats;Research Support, U.S. Gov't, Non-P.H.S.;Neocortex;Synaptic Transmission;Patch-Clamp Techniques;Pyramidal Cells;Rats, Wistar;Dendrites;Potassium;Action Potentials;21 Neurophysiology;Somatosensory Cortex;Interneurons;24 Pubmed search results 2008;Neural Inhibition;Research Support, Non-U.S. Gov't}, Medline = {20102820}, Month = {1}, Nlm_Id = {0404511}, Number = {5451}, Organization = {Department of Neurobiology, The Weizmann Institute for Science, 76100 Rehovot, Israel.}, Pages = {273-8}, Pii = {8184}, Pubmed = {10634775}, Title = {Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex}, Uuid = {D285BBF4-18F9-4E42-B2BB-3A4F2BE23858}, Volume = {287}, Year = {2000}} @article{Gurden:2006, Abstract = {Functional imaging signals arise from metabolic and hemodynamic activity, but how these processes are related to the synaptic and electrical activity of neurons is not well understood. To provide insight into this issue, we used in vivo imaging and simultaneous local pharmacology to study how sensory-evoked neural activity leads to intrinsic optical signals (IOS) in the well-defined circuitry of the olfactory glomerulus. Odor-evoked IOS were tightly coupled to release of glutamate and were strongly modulated by activation of presynaptic dopamine and GABA-B receptors. Surprisingly, IOS were independent of postsynaptic transmission through ionotropic or metabotropic glutamate receptors, but instead were inhibited when uptake by astrocytic glutamate transporters was blocked. These data suggest that presynaptic glutamate release and uptake by astrocytes form a critical pathway through which neural activity is linked to metabolic processing and hence to functional imaging signals.}, Author = {Gurden, Hirac and Uchida, Naoshige and Mainen, Zachary F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {gamma-Aminobutyric Acid;Receptors, Glutamate;Dopamine;Presynaptic Terminals;Rats, Long-Evans;Astrocytes;Animals;Rats;Glutamic Acid;Synaptic Transmission;Cell Communication;Cerebrovascular Circulation;research support, non-u.s. gov't;Receptors, GABA-B;Olfactory Bulb;Receptors, Dopamine;Excitatory Amino Acid Transporter 1;21 Neurophysiology;Light;research support, n.i.h., extramural;24 Pubmed search results 2008;Excitatory Amino Acid Transporter 2;Energy Metabolism;Models, Neurological;Optics}, Month = {10}, Nlm_Id = {8809320}, Number = {2}, Organization = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York, 11724, USA.}, Pages = {335-45}, Pii = {S0896-6273(06)00587-3}, Pubmed = {17046695}, Title = {Sensory-evoked intrinsic optical signals in the olfactory bulb are coupled to glutamate release and uptake}, Uuid = {2F535B87-E34E-4090-BBD8-DE389D4BE440}, Volume = {52}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.07.022}} @article{Gurevich:2002, Abstract = {Arrestins are adaptor proteins involved in homologous desensitization and trafficking of G protein-coupled receptors. Arrestins bind to activated phosphorylated receptors thus precluding further signal transduction. Two subtypes of non-visual arrestins, arrestin2 and arrestin3, have been cloned. Recently, specificity of various receptors to arrestins and differences in kinetics of receptor desensitization mediated by arrestins have been demonstrated. Both arrestins are expressed in the rat brain. However, quantitative assessment of their expression and detailed distribution are lacking. Here, we used quantitative ribonuclease protection assay and western blot to measure arrestin2 and arrestin3 mRNA and protein in the rat brain during postnatal development. In situ hybridization histochemistry was employed to study the detailed distribution of arrestin mRNAs in the adult and developing brain. Both arrestins were expressed from birth in all regions studied. Arrestin2 mRNA levels increased with development until the 14th postnatal day and then decreased, whereas arrestin2 protein levels continued to rise. Arrestin3 mRNA was maximal in neonates and then decreased, while arrestin3 protein changed little. In newborns and adults, the concentration of arrestin2 mRNA was two- to three-fold higher than that of arrestin3. In neonates, the excess of the arrestin2 protein over arrestin3 was commensurate with the excess of the arrestin2 mRNA (three-fold) but in the adult, the ratio was much higher (10-20-fold). Each arrestin demonstrated a unique distribution, although in many areas there was overlap suggesting co-localization. Both arrestins were highly expressed in the cortex and hippocampus. Arrestin2 was abundant in the thalamus, particularly in the anterior, intralaminar, and midline nuclei, while arrestin3 was abundant in the medial habenular. Arrestin3 was relatively abundant in most hypothalamic nuclei and extended amygdala. In the developing brain, arrestin3 was highly expressed in the subventricular zone, whereas arrestin2 was more abundant in differentiated areas.Our data demonstrate that arrestin2 is the major arrestin subtype in the rat brain, although arrestin3 is expressed in specific cell populations including postnatal proliferative zones. Because each arrestin appears to mediate receptor desensitization in a specific way, different kinetics of trafficking of the same receptor should be expected in different cells due to varying arrestin2/arrestin3 ratios. Thus, the response of receptors to specific drugs stimulating or blocking these receptors may depend on complement of arrestins in their target cells. 0306-4522 Journal Article}, Author = {Gurevich, E. V. and Benovic, J. L. and Gurevich, V. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuroscience}, Keywords = {Pregnancy;Animals;Brain/cytology/*growth &development/*metabolism;Neurons/cytology/*metabolism;Cell Differentiation/genetics;Rats;Receptors, Cell Surface/*metabolism;Comparative Study;Female;C abstr;Rats, Sprague-Dawley;In Situ Hybridization;Animals, Newborn;Blotting, Western;Phosphoproteins/genetics/*metabolism;Protein Transport/physiology;Support, U.S. Gov't, P.H.S.;GTP-Binding Proteins/*metabolism;Gene Expression Regulation, Developmental/*physiology;04 Adult neurogenesis factors;RNA, Messenger/metabolism;Arrestins/genetics/*metabolism;Signal Transduction/physiology;Aging/genetics/metabolism}, Number = {3}, Organization = {Sun Health Research Institute, Sun City, AZ 85351, USA. eugenia.gurevich\@mcmail.vanderbilt.edu}, Pages = {421-36}, Pubmed = {11823056}, Title = {Arrestin2 and arrestin3 are differentially expressed in the rat brain during postnatal development}, Uuid = {F0B5CE1E-6788-45E9-B433-CE2A438F36B1}, Volume = {109}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11823056}} @article{Gutierrez-Mecinas:2005, Abstract = {Periglomerular cells (PG) are interneurons of the olfactory bulb (OB) that modulate the first synaptic relay of the olfactory information from the olfactory nerve to the dendrites of the bulbar principal cells. Previous investigations have pointed to the heterogeneity of these interneurons and have demonstrated the presence of two different types of PG. In the rat OB, type 1 PG receive synaptic contacts from the olfactory axons and are gamma-aminobutyric acid (GABA)-ergic, whereas type 2 PG do not receive synaptic contacts from the olfactory axons and are GABA immunonegative. In this study, we analyze and characterize neurochemically a group of PG that has not been previously classified either as type 1 or type 2. These PG are immunoreactive for the neuropeptides somatostatin (SOM) or cholecystokinin (CCK). By using double immunocytochemistry, we demonstrate that neither the SOM- nor the CCK-immunoreactive PG contain GABA immunoreactivity, which is a neurochemical feature of type 1 PG. Moreover, they do not contain the calcium-binding proteins calbindin D-28k and calretinin, which are neurochemical markers of the type 2 PG. Electron microscopy demonstrates that the dendrites of the SOM- and CCK-containing PG are distributed in the synaptic and sensory subcompartments of the glomerular neuropil and receive synaptic contacts from the olfactory axons. Therefore, they should be included in the type 1 group rather than in the type 2. Altogether, these data indicate that the SOM- and the CCK-containing PG may constitute a group of GABA-immunonegative type 1 PG that has not been previously described. These results further extend the high degree of complexity of the glomerular circuitry. J. Comp. Neurol. 489:467-479, 2005. (c) 2005 Wiley-Liss, Inc.}, Author = {Guti\`{e}rrez-Mecinas, Mar{\'\i}a and Crespo, Carlos and Blasco-Ib{\'a}\~{n}ez, Jose{\'e} Miguel and Gracia-Llanes, Francisco Javier and Marqu{\'e}s-Mar{\'\i}, Ana Isabel and Mart{\'\i}nez-Guijarro, Francisco Jos{\'e}}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {0406041}, Number = {4}, Organization = {Departamento de Biolog{\'\i}a Celular, Facultad de Ciencias Biol{\'o}gicas, Universidad de Valencia, E-46100 Burjasot, Spain.}, Pages = {467-79}, Pubmed = {16025459}, Title = {Characterization of somatostatin- and cholecystokinin-immunoreactive periglomerular cells in the rat olfactory bulb}, Uuid = {1797B3C3-A243-438A-B0CF-8F43F195ED0D}, Volume = {489}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20649}} @article{Gutkin:2006, Author = {Gutkin, Boris and Ermentrout, G. Bard}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {comment;24 Pubmed search results 2008;news}, Month = {4}, Nlm_Id = {0410462}, Number = {7087}, Pages = {999-1000}, Pii = {440999a}, Pubmed = {16625182}, Title = {Neuroscience: spikes too kinky in the cortex?}, Uuid = {641D5449-AF6A-4A31-B19C-B8BB748F9659}, Volume = {440}, Year = {2006}, url = {papers/Gutkin_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/440999a}} @article{Gutnick:1983, Abstract = {Lucifer Yellow was injected intracellularly into neurons in slices of guinea pig visual cortex. Dye coupling incidence was significantly decreased in slices that were incubated in a high concentration of carbon dioxide. This effect was probably due to intracellular acidification, since exposure to impermeant acid was not effective. The data are consistent with the hypothesis that carbon dioxide interferes with dye coupling in neocortex through its known action as an uncoupler of electronic coupling through gap junctions.}, Author = {Gutnick, M. J. and Lobel-Yaakov, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Neurons;Visual Cortex;24 Pubmed search results 2008;21 Neurophysiology;Guinea Pigs;21 Gap junctions;Cell Aggregation;research support, u.s. gov't, non-p.h.s. ;Animals;Hydrogen-Ion Concentration;Carbon Dioxide;Intracellular Fluid;Isoquinolines}, Month = {12}, Nlm_Id = {7600130}, Number = {2}, Pages = {197-200}, Pii = {0304-3940(83)90406-8}, Pubmed = {6420731}, Title = {Carbon dioxide uncouples dye-coupled neuronal aggregates in neocortical slices}, Uuid = {5CCD8C7E-211D-4FC8-87B3-E3C2A493E620}, Volume = {42}, Year = {1983}} @article{Gutnick:1985, Abstract = {The fluorescent dye Lucifer Yellow CH was intracellularly injected into neurons in slices of guinea-pig visual neocortex which had been prepared by sectioning either in a plane normal to the pial surface (radial slices) or in a plane parallel to the pial surface (tangential slices). In radial slices 44.3\%of the injections resulted in dye-coupling and the number of cells coupled to the impaled neuron per injection followed a Poisson distribution. In contrast dye-coupling was not observed in tangential slices. Incidence of dye-coupling in slices that had been sectioned in both the radial and tangential planes was the same as in intact radial slices, indicating that slicing in the radial plane induced the formation of pathways for dye movement between neurons. The results suggest that formation and/or strengthening of direct intercellular junctions between neocortical neurons may occur as a specific neuronal response to partial dendrotomy.}, Author = {Gutnick, M. J. and Lobel-Yaakov, R. and Rimon, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Histological Techniques;21 Neurophysiology;research support, non-u.s. gov't ;Guinea Pigs;Fluorescent Dyes;21 Gap junctions;research support, u.s. gov't, non-p.h.s. ;Animals;Isoquinolines;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7605074}, Number = {3}, Pages = {659-66}, Pubmed = {3906427}, Title = {Incidence of neuronal dye-coupling in neocortical slices depends on the plane of section}, Uuid = {2878BEC0-B793-475B-801E-8A21036858B1}, Volume = {15}, Year = {1985}} @article{Haas:1996, Abstract = {Seizures cause a persistent enhancement in dentate synaptic inhibition concurrent with, and possibly compensatory for, seizure-induced hippocampal hyperexcitability. To study this phenomenon, we evoked status epilepticus in rats with systemic kainic acid (KA), and 2 weeks later assessed granule cell inhibition with paired-pulse stimulation of the perforant path (PP) in vitro. Controls demonstrated three components of paired-pulse inhibition: early inhibition (10-30 msec), intermediate facilitation (30-120 msec), and late inhibition (120 msec to 120 sec). After seizures, inhibition in all components was enhanced significantly. The GABA(A) antagonist bicuculline blocked only early enhanced inhibition, demonstrating that both GABA(A) and GABA(B) postsynaptic receptors contribute to seizure-induced enhanced inhibition. In controls, the GABA(B) antagonist CGP 35348 increased both GABA(A) and GABA(B) responses in granule cells, suggesting that CGP 35348 acts presynaptically, blocking receptors that suppress GABA release. In contrast, slices from KA-treated rats were markedly less sensitive to CGP 35348. To test the hypothesis that GABA(B) receptors regulating GABA release are downregulated after seizures, we measured paired-pulse suppression of recurrent IPSPs, or disinhibition, using mossy fiber stimuli. Early disinhibition (<200 msec) was reduced after seizures, whereas late disinhibition remained intact. CGP 35348 blocked the early component of disinhibition in controls and, to a lesser extent, reduced disinhibition in KA slices. However, paired monosynaptic IPSPs recorded intracellularly showed no difference in disinhibition between groups. Our findings indicate that seizure- induced enhancement in dentate inhibition is caused, at least in part, by reduced GABA(B) function in the polysynaptic recurrent inhibitory circuit, resulting in reduced disinhibition and heightened GABA release.}, Author = {Haas, K. Z. and Sperber, E. F. and Moshe, S. L. and Stanton, P. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurosci}, Keywords = {Dentate Gyrus/*physiopathology;Organophosphorus Compounds/pharmacology;Rats;07 Excitotoxicity Apoptosis;Synaptic Transmission;Animal;*Down-Regulation (Physiology);Rats, Sprague-Dawley;Receptors, GABA-B/*metabolism;Kainic Acid;Male;E-5;Support, Non-U.S. Gov't;*Neural Inhibition;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Seizures/chemically induced/*physiopathology;GABA Antagonists/pharmacology;Receptors, GABA-A/antagonists &inhibitors/physiology;Status Epilepticus/chemically induced/physiopathology}, Number = {13}, Organization = {Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461-1602, USA.}, Pages = {4250-60.}, Title = {Kainic acid-induced seizures enhance dentate gyrus inhibition by downregulation of GABA(B) receptors}, Uuid = {B208D28D-D1A7-4B2F-AAE4-F6BC743479BB}, Volume = {16}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8753886}} @article{Haas:2002, Abstract = {The reelin signaling pathway plays a crucial role during the development of laminated structures in the mammalian brain. Reelin, which is synthesized and secreted by Cajal-Retzius cells in the marginal zone of the neocortex and hippocampus, is proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin mRNA by hippocampal Cajal-Retzius cells correlates with the extent of migration defects in the dentate gyrus of patients with temporal lobe epilepsy. These results suggest that reelin is required for normal neuronal lamination in humans, and that deficient reelin expression may be involved in migration defects associated with temporal lobe epilepsy.}, Author = {Haas, Carola A. and Dudeck, Oliver and Kirsch, Matthias and Huszka, Csaba and Kann, Gunda and Pollak, Stefan and Zentner, Josef and Frotscher, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Adolescent;10 Development;10 Hippocampus;Child, Preschool;Humans;Middle Aged;Receptors, LDL;Female;Cell Count;Cell Movement;Hippocampus;Serine Endopeptidases;Cell Adhesion Molecules, Neuronal;RNA, Messenger;Male;Receptors, Lipoprotein;In Situ Hybridization;Extracellular Matrix Proteins;Epilepsy, Temporal Lobe;Neurons;Dentate Gyrus;Adult;Polymerase Chain Reaction;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {22117883}, Month = {7}, Nlm_Id = {8102140}, Number = {14}, Organization = {Institute of Anatomy, Department of Neurosurgery, University of Freiburg, D-79001 Freiburg, Germany. Carola.Haas\@anat.uni-freiburg.de}, Pages = {5797-802}, Pii = {22/14/5797}, Pubmed = {12122039}, Title = {Role for reelin in the development of granule cell dispersion in temporal lobe epilepsy}, Uuid = {8A6426D1-6970-4AB1-83E6-56F0CC4EE9F1}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/20026621}} @article{Haas:2006, Abstract = {The size and shape of neuronal dendritic arbors affect the number and type of synaptic inputs, as well as the complexity and function of brain circuits. In the intact brain, dendritic arbor growth and the development of excitatory glutamatergic synapse are concurrent. Consequently, it has been difficult to resolve whether synaptic inputs drive dendritic arbor development. Here, we test the role of AMPA receptor (AMPAR)-mediated glutamatergic transmission in dendrite growth by expressing peptides corresponding to the intracellular C-terminal domains of AMPAR subunits GluR1 (GluR1Ct) and GluR2 (GluR2Ct) in optic tectal neurons of the Xenopus retinotectal system. These peptides significantly reduce AMPAR synaptic transmission in transfected neurons while leaving visual system circuitry intact. Daily in vivo imaging over 5 days revealed that GluR1Ct or GluR2Ct expression dramatically impaired dendrite growth, resulting in less complex arbors than controls. Time-lapse images collected at 2-h intervals over 6 h show that both GluR1Ct and GluR2Ct decrease branch lifetimes. Ultrastructural analysis indicates that synapses formed onto neurons expressing the GluRCt are less mature than synapses onto control neurons. These data suggest that the failure to form complex arbors is due to reduced stabilization of new synapses and dendritic branches. Although visual stimulation increases dendritic arbor growth rates in control tectal neurons, a weak postsynaptic response to visual experience in GluRCt-expressing cells leads to retraction of branches. These results indicate that AMPAR-mediated transmission underlies experience-dependent dendritic arbor growth by stabilizing branches, and support a competition-based model for dendrite growth.}, Author = {Haas, Kurt and Li, Jianli and Cline, Hollis T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Receptors, Glutamate;Synapses;Dendrites;research support, n.i.h., extramural ;21 Neurophysiology;Protein Structure, Tertiary;Receptors, AMPA;research support, non-u.s. gov't ;Time Factors;Electrophysiology;Synaptic Transmission;Animals;Xenopus laevis;24 Pubmed search results 2008;Neurons;Peptides}, Month = {8}, Nlm_Id = {7505876}, Number = {32}, Organization = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.}, Pages = {12127-31}, Pii = {0602670103}, Pubmed = {16882725}, Title = {AMPA receptors regulate experience-dependent dendritic arbor growth in vivo}, Uuid = {1F1109BC-1941-444D-B9ED-E48C60D95125}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0602670103}} @article{Hablitz:2000, Abstract = {PURPOSE: Identification of changes in neurotransmitter function in animal models of epilepsy provides a basis for rational drug development and an understanding of the mechanisms underlying epileptogenesis. We investigated changes in the efficacy of the benzodiazepine type I agonist zolpidem and the polyamine site N-methyl-D-aspartate receptor antagonist ifenprodil in a rat model of microgyria. METHODS: Neonatal freeze lesions were used to produce a microsulcus in the normally lissencephalic rat neocortex with anatomical similarities to human polymicrogyria. Whole-cell voltage-clamp recordings were made from visually identified layer 2/3 pyramidal cells in acutely prepared brain slices from nonlesioned and lesioned rats. RESULTS: The effect of 20 nmol/L zolpidem on the decay time constant of inhibitory postsynaptic currents was significantly less in neurons from brain slices containing the freeze lesion. A higher concentration (100 nmol/L) of zolpidem was equally efficacious in lesioned and nonlesioned cortex. In lesioned cortex, the threshold for evoking epileptiform discharges was significantly increased in the presence of 10 micromol/L ifenprodil. This effect was significant in both intrinsic hyperexcitability and partial disinhibition with 2 micromol/L bicuculline in lesioned cortex. Ifenprodil had significantly less effect on the threshold of discharges evoked in control cortex in the partial disinhibition model. CONCLUSIONS: The decreased sensitivity of gamma-aminobutyric acid A receptors to 20 nmol/L zolpidem in the freeze-lesion model is consistent with a delayed or arrested maturation in this animal model. These data support a delay in the developmental switch from alpha2 to alpha1 subunits in gamma-aminobutyric acid A receptors of neocortical pyramidal cells in lesioned cortex. The increased ifenprodil sensitivity of the threshold for evoking epileptiform discharges in both control and disinhibited slices containing the microsulcus is explained by a delay in the expression of the 2A (NR2A) N-methyl-D-aspartate receptor subunit. Delayed development may be a hallmark of this type of cortical dysplasia.}, Author = {Hablitz, J. J. and DeFazio, R. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Receptors, N-Methyl-D-Aspartate;Epilepsy;Receptors, GABA-A;21 Epilepsy;Excitatory Postsynaptic Potentials;21 Neurophysiology;Rats;Pyridines;Neural Inhibition;Neocortex;Receptors, GABA;Piperidines;Animals;Patch-Clamp Techniques;24 Pubmed search results 2008;Freezing;Disease Models, Animal}, Medline = {20452154}, Nlm_Id = {2983306R}, Organization = {Department of Neurobiology, University of Alabama at Birmingham, 35294, USA. hablitz\@nrc.uab.edu}, Pages = {S82-5}, Pubmed = {10999525}, Title = {Altered receptor subunit expression in rat neocortical malformations}, Uuid = {980D1525-278B-4EEF-8357-C6B311618008}, Volume = {41 Suppl 6}, Year = {2000}} @article{Hablitz:1998, Abstract = {A freezing probe was placed on the skull of postnatal day (PN) 1 rats to induce formation of a cerebrocortical microsulcus. Experimental studies were performed on PN days 21-24. At that time point, Nissl-stained sections revealed the presence of a microsulcus similar to that described in human dysplastic cortex. Immunocytochemical staining for parvalbumin, calretinin and calbindin indicated a significant decrease in the number of immunoreactive neurons within the microsulcus and non-significant decreases in regions adjacent to the microsulcus. Staining for the glial markers GFAP and vimentin was increased near the microsulcus. Using in vitro brain slices, recordings were made in cortex adjacent to the microsulcus. Epileptiform activity was observed in response to electrical stimulation near the microsulcus. Analysis of the voltage dependence of evoked epileptiform discharges suggested the presence of an inhibitory component. As previously observed in non-lesioned animals, bath application of 4-aminopyridine induced bicuculline-sensitive spontaneous burst discharges in the presence of excitatory amino acid antagonists. These results suggest that cortical freeze lesions associated with abnormal neuronal migration produce a chronic hyperexcitable state. The findings are consistent with a mechanism involving an alteration, not loss, of inhibition in this model.}, Author = {Hablitz, J. J. and DeFazio, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Electric Stimulation;Animals;In Vitro;Humans;Rats;Brain;Neocortex;21 Epilepsy;Epilepsy;Rats, Sprague-Dawley;2-Amino-5-phosphonovalerate;21 Dysplasia-heterotopia;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;N-Methylaspartate;21 Neurophysiology;Freezing;Cerebral Cortex;Membrane Potentials;Laterality;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;Nerve Tissue Proteins}, Medline = {98432477}, Month = {9}, Nlm_Id = {8703089}, Number = {1-2}, Organization = {Department of Neurobiology, University of Alabama at Birmingham, 35294, USA. hablitz\@nrc.uab.edu}, Pages = {75-82}, Pubmed = {9761310}, Title = {Excitability changes in freeze-induced neocortical microgyria}, Uuid = {5CAB00FD-4625-4266-A110-23330D08E00B}, Volume = {32}, Year = {1998}} @article{Hack:2002, Abstract = {During development, Reelin acts on migrating neuronal precursors and controls correct cell positioning in the cortex and other brain structures by a hitherto unidentified mechanism. Here we show that in the postnatal mouse brain, Reelin acts as a detachment signal for chain-migrating interneuron precursors in the olfactory bulb. Neuronal precursors cultured in Matrigel detached from chains and migrated individually in the presence of exogenously added Reelin protein or Reelin-expressing brain tissues. Furthermore, we found that in reeler mutant mice, neuronal precursors accumulated in the olfactory bulb and remained in clusters, indicating that they did not change from tangential chain-migration to radial individual migration. Our data provide direct evidence that Reelin acts as a detachment signal, but not a stop or guidance cue. We propose that Reelin may have comparable functions during development.}, Author = {Hack, Iris and Bancila, Mircea and Loulier, Karine and Carroll, Patrick and Cremer, Harold}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Mice, Inbred BALB C;Cell Differentiation;Signal Transduction;Animals;Gene Expression Regulation, Developmental;Brain Tissue Transplantation;Coculture Techniques;Cell Movement;Mice, Transgenic;COS Cells;Serine Endopeptidases;Cell Adhesion Molecules, Neuronal;Mice, Neurologic Mutants;Prosencephalon;Extracellular Matrix Proteins;Animals, Newborn;Neurons;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Lateral Ventricles;Research Support, Non-U.S. Gov't}, Medline = {22239857}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {NMDA/IBDM, CNRS/INSERM/Universit{\'e} M{\'e}diterran{\'e}e, Campus de Luminy, 13288 Marseille cedex 9, France.}, Pages = {939-45}, Pii = {nn923}, Pubmed = {12244323}, Title = {Reelin is a detachment signal in tangential chain-migration during postnatal neurogenesis}, Uuid = {5EE0E97C-D26B-403D-AB22-CA66FB9D1FC9}, Volume = {5}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn923}} @article{Hack:2005, Abstract = {Adult neurogenesis in mammals is restricted to two small regions, including the olfactory bulb, where GABAergic and dopaminergic interneurons are newly generated throughout the entire lifespan. However, the mechanisms directing them towards a specific neuronal phenotype are not yet understood. Here, we demonstrate the dual role of the transcription factor Pax6 in generating neuronal progenitors and also in directing them towards a dopaminergic periglomerular phenotype in adult mice. We present further evidence that dopaminergic periglomerular neurons originate in a distinct niche, the rostral migratory stream, and are fewer derived from precursors in the zone lining the ventricle. This regionalization of the adult precursor cells is further supported by the restricted expression of the transcription factor Olig2, which specifies transit-amplifying precursor fate and opposes the neurogenic role of Pax6. Together, these data explain both extrinsic and intrinsic mechanisms controlling neuronal identity in adult neurogenesis.}, Author = {Hack, and Saghatelyan, and de Chevigny, and Pfeifer, and Ashery-Padan, and Lledo, and G{\"o}tz,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {01 Adult neurogenesis general;02 Adult neurogenesis migration}, Month = {6}, Nlm_Id = {9809671}, Organization = {[1] GSF-National Research Center for Environment and Health, Institute for Stem Cell Research, Ingolst{\"a}dter Landstr. 1, D-85764 Neuherberg, Germany. [2] These authors contributed equally to this work.}, Pii = {nn1479}, Pubmed = {15951811}, Title = {Neuronal fate determinants of adult olfactory bulb neurogenesis}, Uuid = {D42A890C-9208-46A3-B185-E84038D28E23}, Year = {2005}, url = {papers/Hack_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1479}} @article{Hadj-Sahraoui:2000, Abstract = {Circulating T(4) and T(3) were measured during the first three post-natal weeks in the mouse and found to increase in a triphasic manner. The first increase occurred at post-natal day 6 and was simultaneous with a decrease in bromodeoxyuridine incorporation in areas showing post-natal mitosis. We investigated whether there was a causal relationship between increased thyroid hormone levels and decreased proliferation by inducing hypothyroidism in dams and progeny. Hypothyroidism prolonged mitotic activity in the olfactory bulb, hippocampus, subventricular zone and the cerebellar cortex. This suggests that the increase in T(3) at the end of the first postnatal week is implicated in terminating progenitor proliferation in many parts of the mouse brain. 0304-3940 Journal Article}, Author = {Hadj-Sahraoui, N. and Seugnet, I. and Ghorbel, M. T. and Demeneix, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neurosci Lett}, Keywords = {Hippocampus/metabolism/physiopathology;Pregnancy;Animals;Hypothyroidism/chemically induced/*physiopathology;Triiodothyronine/blood;Olfactory Bulb/metabolism/physiopathology;Cerebellum/metabolism/physiopathology;Female;D pdf;Time Factors;Male;Brain/metabolism/*physiopathology;Support, Non-U.S. Gov't;Bromodeoxyuridine/metabolism;Animals, Newborn;06 Adult neurogenesis injury induced;Mitosis/*physiology;Propylthiouracil/adverse effects;Thyroxine/blood;Mice}, Number = {2}, Organization = {Laboratoire de Physiologie Generale et Comparee, UMR 8572 CNRS, Museum National d'Histoire Naturelle, F-75231, Paris, Cedex, France.}, Pages = {79-82}, Pubmed = {10686382}, Title = {Hypothyroidism prolongs mitotic activity in the post-natal mouse brain}, Uuid = {33FCB3E9-F887-4668-90E6-1F527A1E2194}, Volume = {280}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10686382}} @article{Hagemann:2000, Abstract = {Early postnatal injections of ibotenate into the rat neopallium induce cortical dysplasias mimicking human polymicrogyria which often goes along with seizure disorders. Under in vitro conditions these experimentally induced dysplasias cause widespread hyperexcitability. The underlying mechanisms are as yet not fully understood. Electrophysiologically there is clear evidence of widespread alterations of the excitatory system. Intracellular recordings also showed some changes of the inhibitory system but have concentrated on recordings from focal areas close to the microgyrus. We investigated the integrity of functional inhibition using a paired-pulse paradigm to map the whole ipsilateral hemisphere. In rat cortical slices double-pulses were applied in layer VI/white matter and field potentials recorded in layer II/III. The ratio of the field potential amplitude did not show significant alterations in the dysplasias or their surround as compared with control and sham-injected animals. This result was obtained with two different locations of the dysplasias, excluding a mere areal specific effect. Our results show that despite prominent hyperexcitability in the surround of ibotenate-induced cortical dysplasias the inhibitory network appears to be functionally intact.}, Author = {Hagemann, G. and Redecker, C. and Witte, O. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Epilepsy;Research Support, Non-U.S. Gov't;21 Neurophysiology;Nerve Degeneration;Ibotenic Acid;Rats;Excitatory Amino Acid Agonists;Neural Inhibition;Rats, Wistar;Animals, Newborn;Electrophysiology;Disease Models, Animal;Animals;Cerebral Cortex;24 Pubmed search results 2008;21 Epilepsy}, Medline = {20359603}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Neurology, Heinrich-Heine-University, D-40225 Duesseldorf, Germany. Georg.Hagemann\@uni-duesseldorf.de}, Pages = {600-3}, Pubmed = {10899234}, Title = {Intact functional inhibition in the surround of experimentally induced focal cortical dysplasias in rats}, Uuid = {60817FB2-3D1F-4966-9FB6-DD2E9F9C1D7D}, Volume = {84}, Year = {2000}} @article{Hagemann:2003, Abstract = {Electrophysiological studies in humans and animal models have revealed an intrinsic epileptogenicity of cortical dysplasias which are a frequent cause of drug-resistant epilepsy. An imbalance of inhibition and excitation has been causative related. Receptor-binding studies in rodents demonstrated reduced binding to GABA and increased binding to glutamate receptors within cortical dysplasias and increments of AMPA- and kainate-receptor binding in its surround. Immunohistochemically a differential downregulation of GABA(A) receptor subunits could be demonstrated in widespread areas within and around dysplasias. As receptor binding critically depends on receptor subunit composition the observed changes in binding properties might be related to this. Here, we immunohistochemically analyzed the regional expression of four NMDA receptor subunits and two major AMPA- and kainate-receptor complexes in adult rats after neonatal freeze lesions. These lesions are characterized by a three- to four-layered cortex and a microsulcus which mimic human polymicrogyria. Using antibodies against NR1, NR2A, NR2B, NR2D, GluR2,3, and GluR5,6,7 receptor subunits we demonstrated a pronounced disturbance of cortical immunostaining pattern in the cortical malformation. These changes reflected the structural disorganization of the microgyrus with some distortion of the apical dendrites of paramicrogyral pyramidal cells, a decrease and disorganization of cells at the bottom of the microsulcus, and an inflection of apical dendrites toward the microsulcus. The neuronal staining pattern of large pyramidal cells in the neighborhood of the dysplasia did not differ for any subunit investigated. No remote or widespread changes of glutamate-receptor subunit distribution could be detected. The lack of gross and/or widespread alterations of glutamate-receptor subunit distribution in the surround of focal cortical dysplasia suggests the presence of other or additional mechanisms underlying the increased excitatory neurotransmitter binding and excitability in cortical malformations.}, Author = {Hagemann, G. and Kluska, M. M. and Redecker, C. and Luhmann, H. J. and Witte, O. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Excitatory Postsynaptic Potentials;Receptors, Glutamate;Protein Subunits;Animals;Binding Sites;Rats;Synaptic Transmission;21 Epilepsy;Epilepsy;Receptors, AMPA;Pyramidal Cells;Rats, Wistar;Animals, Newborn;Action Potentials;Nervous System Malformations;Cerebral Cortex;21 Neurophysiology;Receptors, Kainic Acid;24 Pubmed search results 2008;Immunohistochemistry;Receptors, N-Methyl-D-Aspartate;Neural Inhibition;Binding, Competitive;Research Support, Non-U.S. Gov't}, Medline = {22542189}, Nlm_Id = {7605074}, Number = {4}, Organization = {Department of Neurology, Friedrich-Schiller-University, Philosophenweg 3, D-07740, Jena, Germany. hagemann\@med.uni-jena.de}, Pages = {991-1002}, Pii = {S0306452202009594}, Pubmed = {12654351}, Title = {Distribution of glutamate receptor subunits in experimentally induced cortical malformations}, Uuid = {EF43AAA0-C1EB-48CF-BF8E-551A30A4C80B}, Volume = {117}, Year = {2003}} @article{Hagino-Yamagishi:1999, Abstract = {The expression of Brain-2, a POU domain transcription factor, was examined in the developing olfactory bulb. Brain-2 was expressed mainly in the output neurons, mitral cell and tufted cells in the main olfactory bulb (MOB), and mitral/tufted cells (MT cells) in the accessory olfactory bulb (AOB). It was not expressed in granular cells in either the MOB or the AOB. Our results suggest that Brain-2 was specifically expressed in output neurons but not in interneurons in the developing olfactory bulb. Brain-2 may play a role in the development of these output neurons.}, Author = {Hagino-Yamagishi, K. and Minamikawa-Tachino, R. and Ichikawa, M. and Yazaki, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Antimetabolites;13 Olfactory bulb anatomy;Brain Chemistry/physiology;Fluorescent Antibody Technique;Olfactory Receptor Neurons/chemistry/*physiology;Female;DNA-Binding Proteins/*analysis/*biosynthesis/immunology;Olfactory Bulb/*chemistry/*cytology/embryology;Animal;Pregnancy;I abstr;Transcription Factors/analysis/biosynthesis/immunology;Support, Non-U.S. Gov't;Bromodeoxyuridine;Antibodies;Nerve Tissue Proteins/*analysis/*biosynthesis/immunology;Mice}, Number = {1-2}, Organization = {Department of Ultrastructural Research, Tokyo Metropolitan Institute of Medical Science, Honkomagome 3-18-22, Bunkyo-ku, Tokyo 113, Japan. yamagishi\@rinshoken.or.jp}, Pages = {133-7.}, Title = {Expression of brain-2 in the developing olfactory bulb}, Uuid = {14A9990D-010F-4D0D-8BED-C811FAF3BBD8}, Volume = {113}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10064882%20http://www.elsevier.com:80/cgi-bin/cas/tree/store/bresd/cas_sub/browse/browse.cgi?year=1999&volume=113&issue=1-2&aid=60733}} @article{Hahnloser:2002, Abstract = {Sequences of motor activity are encoded in many vertebrate brains by complex spatio-temporal patterns of neural activity; however, the neural circuit mechanisms underlying the generation of these pre-motor patterns are poorly understood. In songbirds, one prominent site of pre-motor activity is the forebrain robust nucleus of the archistriatum (RA), which generates stereotyped sequences of spike bursts during song and recapitulates these sequences during sleep. We show that the stereotyped sequences in RA are driven from nucleus HVC (high vocal centre), the principal pre-motor input to RA. Recordings of identified HVC neurons in sleeping and singing birds show that individual HVC neurons projecting onto RA neurons produce bursts sparsely, at a single, precise time during the RA sequence. These HVC neurons burst sequentially with respect to one another. We suggest that at each time in the RA sequence, the ensemble of active RA neurons is driven by a subpopulation of RA-projecting HVC neurons that is active only at that time. As a population, these HVC neurons may form an explicit representation of time in the sequence. Such a sparse representation, a temporal analogue of the 'grandmother cell' concept for object recognition, eliminates the problem of temporal interference during sequence generation and learning attributed to more distributed representations.}, Author = {Hahnloser, Richard H. R. and Kozhevnikov, Alexay A. and Fee, Michale S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Songbirds;Vocalization, Animal;24 Pubmed search results 2008;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;Electrophysiology;Interneurons;Animals;Brain;Male;Neurons;Sleep}, Month = {9}, Nlm_Id = {0410462}, Number = {6902}, Organization = {Biological Computation Research Department, Bell Laboratories, Lucent Technologies, Murray Hill, New Jersey 07974, USA.}, Pages = {65-70}, Pii = {nature00974}, Pubmed = {12214232}, Title = {An ultra-sparse code underlies the generation of neural sequences in a songbird}, Uuid = {F5336DDE-D200-4E33-AD05-D6C6FE149785}, Volume = {419}, Year = {2002}, url = {papers/Hahnloser_Nature2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature00974}} @article{Haider:1997, Abstract = {A novel methodology for labeling, isolation, and detection of nucleic acids is described. Nucleic acid isolation is based on in vivo or in vitro incorporation of BrU or BrdU to either RNA or DNA, respectively, followed by immunoprecipitation of the labeled nucleic acid utilizing anti-BrdU MoAb, which crossreacts with BrU, attached to solid particles. Filter-bound bromine-labeled DNA or RNA was detected by immunoblotting with anti-BrdU MoAb, by a combined Southern/Western or Northern/Western approach, respectively. This method was applied to isolate and detect rRNA and mRNA from human cells, plasmid DNA from bacterial cells, and in vitro synthesized DNA. Newly transcribed BrU-labeled mRNA was recovered from the immunoprecipitates and analyzed by RT-PCR to study phorbol ester-mediated regulation of interleukin 1 gene transcription in human leukemic HL-60 or lymphoma U937 cells. The plasmid DNAs were isolated by immunoprecipitation from transformed bacterial cultures that were grown in the presence of BrdU and were detected immunochemically on filters. Likewise, the products of RT-PCR and Klenow polymerase-catalyzed DNA synthesis in which dTTP was replaced with BrdUTP were detected by immunoblotting. Since the method allows one to selectively separate or detect nucleic acids only synthesized during a pulse of the precursor, it can uniquely be used to identify nascent gene transcripts or the transcripts synthesized within specific time windows, e.g., after induction of differentiation, carcinogenesis, or drug treatment, and distinguish such transcripts from preexisting ones. In addition, this approach offers a simple and inexpensive alternative for preparing labeled DNA as well as RNA probes for use in a variety of hybridization protocols. Due to the low toxicity of BrU and BrdU, this approach can be used in analysis of gene transcription or DNA replication in vivo.}, Author = {Haider, S. R. and Juan, G. and Traganos, F. and Darzynkiewicz, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0014-4827}, Journal = {Exp Cell Res}, Keywords = {23 dNTPs-Brdu;DNA, Bacterial;Molecular Probe Techniques;RNA;Nucleic Acids;Humans;Sensitivity and Specificity;23 Technique;Uridine;Cross Reactions;Research Support, U.S. Gov't, P.H.S.;Antibody Specificity;Antibodies, Monoclonal;Tumor Cells, Cultured;Polymerase Chain Reaction;Deoxyuracil Nucleotides;24 Pubmed search results 2008;HL-60 Cells;Bromodeoxyuridine;Precipitin Tests;Research Support, Non-U.S. Gov't}, Medline = {97405876}, Month = {8}, Nlm_Id = {0373226}, Number = {2}, Organization = {The Cancer Research Institute, New York Medical College, Valhalla 10595, USA. raza\_haider\@nymc.edu}, Pages = {498-506}, Pii = {S0014482797936442}, Pubmed = {9260920}, Title = {Immunoseparation and immunodetection of nucleic acids labeled with halogenated nucleotides}, Uuid = {2D70F25F-8214-47DB-B095-FBB0412BE385}, Volume = {234}, Year = {1997}, url = {papers/Haider_ExpCellRes1997.pdf}} @article{Haider:2007, Abstract = {Spontaneous activity within local circuits affects the integrative properties of neurons and networks. We have previously shown that neocortical network activity exhibits a balance between excitatory and inhibitory synaptic potentials, and such activity has significant effects on synaptic transmission, action potential generation, and spike timing. However, whether such activity facilitates or reduces sensory responses has yet to be clearly determined. We examined this hypothesis in the primary visual cortex in vivo during slow oscillations in ketamine-xylazine anesthetized cats. We measured network activity (Up states) with extracellular recording, while simultaneously recording postsynaptic potentials (PSPs) and action potentials in nearby cells. Stimulating the receptive field revealed that spiking responses of both simple and complex cells were significantly enhanced (>2-fold) during network activity, as were spiking responses to intracellular injection of varying amplitude artificial conductance stimuli. Visually evoked PSPs were not significantly different in amplitude during network activity or quiescence; instead, spontaneous depolarization caused by network activity brought these evoked PSPs closer to firing threshold. Further examination revealed that visual responsiveness was gradually enhanced by progressive membrane potential depolarization. These spontaneous depolarizations enhanced responsiveness to stimuli of varying contrasts, resulting in an upward (multiplicative) scaling of the contrast response function. Our results suggest that small increases in ongoing balanced network activity that result in depolarization may provide a rapid and generalized mechanism to control the responsiveness (gain) of cortical neurons, such as occurs during shifts in spatial attention.}, Author = {Haider, Bilal and Duque, Alvaro and Hasenstaub, Andrea R. and Yu, Yuguo and McCormick, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Electric Stimulation;Photic Stimulation;Animals;Nonlinear Dynamics;Patch-Clamp Techniques;Female;Reaction Time;research support, non-u.s. gov't;Nerve Net;Action Potentials;21 Neurophysiology;Neurons;research support, n.i.h., extramural;24 Pubmed search results 2008;Visual Cortex;Cats;Dose-Response Relationship, Radiation;Excitatory Postsynaptic Potentials}, Month = {6}, Nlm_Id = {0375404}, Number = {6}, Organization = {Department of Neurobiology, Yale University, School of Medicine, New Haven, Connecticut 06510, USA.}, Pages = {4186-202}, Pii = {01114.2006}, Pubmed = {17409168}, Title = {Enhancement of visual responsiveness by spontaneous local network activity in vivo}, Uuid = {CA38D336-A8F2-4634-81D2-CD40646BC5B8}, Volume = {97}, Year = {2007}, url = {papers/Haider_JNeurophysiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01114.2006}} @article{Haider:2006, Abstract = {The recurrent excitatory and inhibitory connections between and within layers of the cerebral cortex are fundamental to the operation of local cortical circuits. Models of cortical function often assume that recurrent excitation and inhibition are balanced, and we recently demonstrated that spontaneous network activity in vitro contains a precise balance of excitation and inhibition; however, the existence of a balance between excitation and inhibition in the intact and spontaneously active cerebral cortex has not been directly tested. We examined this hypothesis in the prefrontal cortex in vivo, during the slow (<1 Hz) oscillation in ketamine-xylazine-anesthetized ferrets. We measured persistent network activity (Up states) with extracellular multiple unit and local field potential recording, while simultaneously recording synaptic currents in nearby cells. We determined the reversal potential and conductance change over time during Up states and found that the body of Up state activity exhibited a steady reversal potential (-37 mV on average) for hundreds of milliseconds, even during substantial (21 nS on average) changes in membrane conductance. Furthermore, we found that both the initial and final segments of the Up state were characterized by significantly more depolarized reversal potentials and concomitant increases in excitatory conductance, compared with the stable middle portions of Up states. This ongoing temporal evolution between excitation and inhibition, which exhibits remarkable proportionality within and across neurons in active local networks, may allow for rapid transitions between relatively stable network states, permitting the modulation of neuronal responsiveness in a behaviorally relevant manner.}, Author = {Haider, Bilal and Duque, Alvaro and Hasenstaub, Andrea R. and McCormick, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, n.i.h., extramural ;Animals;Ferrets;Cells, Cultured;Synaptic Transmission;Neocortex;Biological Clocks;Male;research support, non-u.s. gov't ;Computer Simulation;Nerve Net;Action Potentials;21 Neurophysiology;21 Circuit structure-function;Neurons;24 Pubmed search results 2008;Neural Inhibition;Models, Neurological;Excitatory Postsynaptic Potentials}, Month = {4}, Nlm_Id = {8102140}, Number = {17}, Organization = {Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Pages = {4535-45}, Pii = {26/17/4535}, Pubmed = {16641233}, Title = {Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition}, Uuid = {DDEC45B7-F3D8-4622-8D15-6EB790B1CAFE}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5297-05.2006}} @article{Hailer:1997, Abstract = {Entorhinal cortex lesion (ECL) leads to anterograde degeneration of perforant path axons and is known to induce a rapid and intense reaction of astrocytes and microglial cells in the deafferented dentate gyrus. Phagocytosis of degenerating axons involves the establishment and maintenance of cell-matrix and cell-cell interactions by activated glial cells. It was thus our aim to investigate whether the process of axon phagocytosis is accompanied by the expression of adhesion molecules on activated microglial cells or reactive astrocytes, as such molecules mediate bot cell-matrix and cell-cell interactions. We found that the integrin adhesion molecules leukocyte function antigen-1 (LFA-1), very late antigen-4 (VLA-4), and the ligand for LFA-1, intercellular adhesion molecule-1 (ICAM-1), were expressed on microglial cells accumulating in the outer molecular layer of the deafferented dentate gyrus. This upregulation of adhesion molecule expression on microglial cells showing morphological criteria of activation occurred rapidly following ECL, reached its peak at 3 days post lesion (dpl), and gradually returned to control levels after 9 dpl. Astrocytes were never labeled by antibodies directed against these adhesion molecules. Prelabeling of the perforant path with a fluorescent tracer and subsequent ECL led to phagocytosis of fluorescent-labeled axonal debris by cells that were located in the outer molecular layer and showed typical microglial morphology. Double-fluorescence labeling demonstrated that microglial cells engaged in the phagocytosis of axonal debris expressed LFA-1, VLA-4, and the LFA-1-ligand ICAM-1. In conclusion, our results demonstrate that anterograde degeneration of perforant path axons results in adhesion molecule expression on activated microglial cells engaged in axon phagocytosis. The expression of such molecules could represent a mechanism that retains activated microglia in areas of axonal degeneration and perhaps enables the interaction of microglial cells with each other or with other immunocompetent cells.}, Author = {Hailer, N. P. and Bechmann, I. and Heizmann, S. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {1050-9631}, Journal = {Hippocampus}, Keywords = {Research Support, Non-U.S. Gov't;Phagocytosis;Nerve Degeneration;Animals;Intercellular Adhesion Molecule-1;Rats;Integrins;Fluorescent Antibody Technique;Microglia;Female;Denervation;Axons;Rats, Wistar;Not relevant;11 Glia;Male;Support, Non-U.S. Gov't;Receptors, Lymphocyte Homing;Dentate Gyrus;Integrin alpha4beta1;Cell Adhesion Molecules;Lymphocyte Function-Associated Antigen-1;Anti-Allergic Agents}, Medline = {97372290}, Nlm_Id = {9108167}, Number = {3}, Organization = {Department of Cell- and Neurobiology, Humboldt University Hospital Charit{\'e}, Berlin, Federal Republic of Germany. hailer\@rz.charite.hu-berlin.de}, Pages = {341-9}, Pubmed = {9228530}, Title = {Adhesion molecule expression on phagocytic microglial cells following anterograde degeneration of perforant path axons}, Uuid = {CD4F76B1-7A61-4116-AD66-BD86A77C3C0E}, Volume = {7}, Year = {1997}} @article{Hains:2006, Abstract = {Traumatic spinal cord injury (SCI) results not only in motor impairment but also in chronic central pain, which can be refractory to conventional treatment approaches. It has been shown recently that in models of peripheral nerve injury, spinal cord microglia can become activated and contribute to development of pain. Considering their role in pain after peripheral injury, and because microglia are known to become activated after SCI, we tested the hypothesis that activated microglia contribute to chronic pain after SCI. In this study, adult male Sprague Dawley rats underwent T9 spinal cord contusion injury. Four weeks after injury, when lumbar dorsal horn multireceptive neurons became hyperresponsive and when behavioral nociceptive thresholds were decreased to both mechanical and thermal stimuli, intrathecal infusions of the microglial inhibitor minocycline were initiated. Electrophysiological experiments showed that minocycline rapidly attenuated hyperresponsiveness of lumbar dorsal horn neurons. Behavioral data showed that minocycline restored nociceptive thresholds, at which time spinal microglial cells assumed a quiescent morphological phenotype. Levels of phosphorylated-p38 were decreased in SCI animals receiving minocycline. Cessation of delivery of minocycline resulted in an immediate return of pain-related phenomena. These results suggest an important role for activated microglia in the maintenance of chronic central below-level pain after SCI and support the newly emerging role of non-neuronal immune cells as a contributing factor in post-SCI pain.}, Author = {Hains, Bryan C. and Waxman, Stephen G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {16}, Organization = {Department of Neurology, Center for Neuroscience and Regeneration Research, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Pages = {4308-17}, Pii = {26/16/4308}, Pubmed = {16624951}, Title = {Activated microglia contribute to the maintenance of chronic pain after spinal cord injury}, Uuid = {1840699A-DAAC-4A53-A14D-9E91FD840516}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0003-06.2006}} @article{Halene:1999, Abstract = {Retroviral vectors based on the Moloney murine leukemia virus (MoMuLV) are currently the most commonly used vehicles for stable gene transfer into mammalian hematopoietic cells. But, even with reasonable transduction efficiency, expression only occurs in a low percentage of transduced cells and decreases to undetectable levels over time. We have previously reported the modified MND LTR (myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted) to show increased expression frequency and decreased methylation in transduced murine embryonic stem cells and hematopoietic stem cells. We have now compared expression of the enhanced green fluorescent protein (eGFP) from a vector using the MoMuLV LTR (LeGFPSN) with that from the modified vector (MNDeGFPSN) in mature hematopoietic and lymphoid cells in the mouse bone marrow transplant (BMT) model. In primary BMT recipients, we observed a higher frequency of expression from the MND LTR (20\%to 80\%) in hematopoietic cells of all lineages in spleen, bone marrow, thymus, and blood compared with expression from the MoMuLV LTR (5\%to 10\%). Expression from the MND LTR reached 88\%in thymic T lymphocytes and 54\%in splenic B lymphocytes for up to 8 months after BMT. The mean fluorescence intensity of the individual cells, indicating the amount of protein synthesized, was 6- to 10-fold higher in cells expressing MNDeGFPSN compared with cells expressing LeGFPSN. Transduction efficiencies determined by DNA polymerase chain reaction of vector copy number were comparable for the 2 vectors. Therefore, the MND vector offers an improved vehicle for reliable gene expression in hematopoietic cells.}, Author = {Halene, S. and Wang, L. and Cooper, R. M. and Bockstoce, D. C. and Robbins, P. B. and Kohn, D. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Transduction, Genetic;Gene Dosage;Animals;Bone Marrow Transplantation;Lymphocytes;Female;Mice, Inbred C57BL;11 Glia;Retroviridae;Time Factors;Green Fluorescent Proteins;Male;Leukemia Virus, Murine;Research Support, U.S. Gov't, P.H.S.;Genetic Vectors;Gene Therapy;3T3 Cells;Gene Transfer Techniques;Polymerase Chain Reaction;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {20021682}, Month = {11}, Nlm_Id = {7603509}, Number = {10}, Organization = {Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA.}, Pages = {3349-57}, Pubmed = {10552944}, Title = {Improved expression in hematopoietic and lymphoid cells in mice after transplantation of bone marrow transduced with a modified retroviral vector}, Uuid = {8AC33AC9-260F-48F1-B6EC-168A17DDE914}, Volume = {94}, Year = {1999}} @article{Hallbergson:2003, Abstract = {The brain shows limited ability to repair itself, but neurogenesis in certain areas of the adult brain suggests that neural stem cells may be used for structural brain repair. It will be necessary to understand how neurogenesis in the adult brain is regulated to develop strategies that harness neural stem cells for therapeutic use. 0021-9738 Journal Article Review Review, Tutorial}, Author = {Hallbergson, A. F. and Gnatenco, C. and Peterson, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {J Clin Invest}, Keywords = {B pdf;*Stem Cell Transplantation;02 Adult neurogenesis migration;Neurons/*physiology;Brain/*physiology;Human;Brain Injuries/physiopathology/*therapy;Brain Diseases/physiopathology/*therapy;Animals;Stem Cells/*physiology}, Number = {8}, Organization = {Neural Repair and Neurogenesis Laboratory, Department of Neuroscience, The Chicago Medical School, 3333 Green Bay Road, North Chicago, Illinois 60064, USA.}, Pages = {1128-33}, Title = {Neurogenesis and brain injury: managing a renewable resource for repair}, Uuid = {CD111597-8CC7-4669-B9CD-6800F3426D9B}, Volume = {112}, Year = {2003}, url = {papers/Hallbergson_JClinInvest2003.pdf}} @article{Halliday:1992, Abstract = {The development of the rat striatum was investigated using a combination of two histochemically distinguishable retrovirus vectors. Using this method, it was possible to identify clonal boundaries within the embryonic striatum and thus determine patterns of proliferation, migration, and some lineal relationships. Several novel aspects of striatal histogenesis were discovered. Striatal progenitor cells do not exhibit a stem cell pattern of division between embryonic day 15 (E15) and E19; a progenitor-progeny relationship appears to exist for ventricular zone and subventricular zone (SVZ) cells; striatal progenitors produce a variety of clone types; some SVZ cells migrate radially, and some migrate tangentially within the SVZ; and radial glia and presumptive neurons can occur in the same clone. eng Journal Article}, Author = {Halliday, A. L. and Cepko, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Journal = {Neuron}, Keywords = {Pregnancy;B abstr;Escherichia coli/enzymology;Rats;Cells, Cultured;beta-Galactosidase/analysis/genetics;Female;Animal;02 Adult neurogenesis migration;Time Factors;Genetic Vectors;DNA, Bacterial/genetics;Support, Non-U.S. Gov't;Retroviridae/genetics;Neuroglia/cytology/physiology;DNA, Viral/genetics;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Stem Cells/*cytology/physiology;Corpus Striatum/*cytology/*embryology/enzymology;Immunohistochemistry;Cell Differentiation/physiology;Neurons/cytology/physiology;Alkaline Phosphatase/analysis/genetics}, Number = {1}, Organization = {Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.}, Pages = {15-26.}, Title = {Generation and migration of cells in the developing striatum}, Uuid = {87B07A86-F3CA-4D06-95FD-0AD1F544E396}, Volume = {9}, Year = {1992}} @article{Halloran:2006, Abstract = {Repulsive signaling plays a prominent role in regulating cell-cell interactions and is fundamental to multiple developmental processes. A proper balance between repulsion from and adhesion to other cells or the extracellular matrix is also important. Semaphorin-Plexin and ephrin-Eph ligand-receptor pairs compose two major repulsive signaling systems. Recent advances have elucidated mechanisms by which Semaphorin-Plexin and ephrin-Eph signaling control repulsion versus adhesion. Semaphorins act through a complex signaling pathway to inhibit integrin-mediated adhesion, allowing cell repulsion. Ephrin-Eph interactions can directly mediate cell adhesion and several mechanisms control whether ephrin-Eph binding and signaling induces repulsion or adhesion.}, Author = {Halloran, Mary C. and Wolman, Marc A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0955-0674}, Journal = {Curr Opin Cell Biol}, Keywords = {Models, Biological;10 Development;Cell Adhesion;Cell Adhesion Molecules;Semaphorins;Nerve Tissue Proteins;Signal Transduction;10 circuit formation;research support, n.i.h., extramural;Ephrins;24 Pubmed search results 2008;review}, Month = {10}, Nlm_Id = {8913428}, Number = {5}, Organization = {Department of Zoology, Madison, WI 53706, USA. mchalloran\@wisc.edu}, Pages = {533-40}, Pii = {S0955-0674(06)00121-9}, Pubmed = {16930978}, Title = {Repulsion or adhesion: receptors make the call}, Uuid = {693C6865-741A-4B40-96E1-D34648726817}, Volume = {18}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ceb.2006.08.010}} @article{Hamada:2003, Abstract = {The b-Zip transcription factor MafB is an essential determinant of neural development and an inducer of monocytic differentiation. The MafB protein is expressed in a variety of tissues including the developing spinal cord, retina, myelomonocytic lineages of hematopoietic cells, and peritoneal macrophages. However, the tissue-specific regulatory mechanism of mafB gene expression and its biological relevance have not been examined in detail. Here, we report, for the first time, analysis of the regulatory mechanism and tissue-specific expression of the mafB gene in vivo using transgenic mice. A transgene, containing the 8.2-kb sequence flanking the 5' end of the mafB exon, directed the expression of a GFP reporter gene specifically in the retina, myelomonocytic lineages of hematopoietic cells, peritoneal macrophages and the ventral spinal cord. In situ hybridization analysis showed that the reporter gene expression specifically recapitulates the endogenous expression profile of mafB in the retina and spinal cord. FACS analysis revealed that the Gr-1, Mac-1 and F4/80 antigens were present on most of the GFP-positive hematopoietic cells from transgenic adult bone marrow and spleen. On the other hand, B220 CD4, 8, and Ter119 cells were almost absent from among the GFP-positive cells examined. These observations suggest that gene regulatory regions located in the 8.2-kb upstream region of mafB are responsible for directing mafB expression in the retina, myelomonocytic lineages, peritoneal macrophages and the ventral spinal cord.}, Author = {Hamada, Michito and Moriguchi, Takashi and Yokomizo, Tomomasa and Morito, Naoki and Zhang, Chuan and Takahashi, Satoru}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0021-924X}, Journal = {J Biochem (Tokyo)}, Keywords = {Retina;Cell Differentiation;5' Untranslated Regions;Gene Dosage;Monocytes;DNA-Binding Proteins;Gene Expression Regulation;Macrophages;Animals;Transcription Factors;Brain;Avian Proteins;Mice, Transgenic;RNA, Messenger;Peritoneum;11 Glia;Green Fluorescent Proteins;Spinal Cord;Bone Marrow;Cell Lineage;Oncogene Proteins;Organ Specificity;Mice;Luminescent Proteins;Genes, Reporter;Research Support, Non-U.S. Gov't}, Medline = {22846658}, Month = {8}, Nlm_Id = {0376600}, Number = {2}, Organization = {Department of Anatomy, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba 305-8575.}, Pages = {203-10}, Pubmed = {12966068}, Title = {The mouse mafB 5'-upstream fragment directs gene expression in myelomonocytic cells, differentiated macrophages and the ventral spinal cord in transgenic mice}, Uuid = {41AF6DF3-A7D4-41B3-9FB3-A0DB93796B59}, Volume = {134}, Year = {2003}} @article{Hamel:2005, Abstract = {Brevican, a proteoglycan of the lectican family, inhibits neurite outgrowth and may also stabilize synapses. Little is known about its expression or function in vitro. This study seeks to determine whether a brevican-containing matrix is present in neural cultures, and if so, how the production of brevican may be modulated. To accomplish this, the content of brevican and its proteolytic fragments were measured in primary cultures of neurons, astrocytes and microglia after treatment with cytokines. These experiments revealed that astrocytes and neurons express several isoforms of brevican, whereas microglia do not produce this proteoglycan. Cleavage fragments of brevican were found primarily in neuronal and astrocyte culture medium. ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs), a protease that selectively cleaves lecticans, was detected in cultures of neurons, astrocytes and microglia. When astrocytes were challenged with various cytokines, it was found that treatment with transforming growth factor beta (TGFbeta) resulted in a marked increase in intact brevican in the culture medium that was accompanied by a trend for a decrease in ADAMTS-generated fragments of brevican and apparent ADAMTS activity. Thus, TGFbeta may play a role in neuronal plasticity through its regulation of brevican and the activity of the ADAMTSs.}, Author = {Hamel, Michelle G. and Mayer, Joanne and Gottschall, Paul E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Cell Differentiation;Animals;Astrocytes;Cells, Cultured;Carrier Proteins;Rats;Neuronal Plasticity;Coculture Techniques;Up-Regulation;Transforming Growth Factor beta;Microglia;Peptide Hydrolases;Cell Communication;Rats, Sprague-Dawley;Neurites;Brain;Extracellular Matrix;Procollagen N-Endopeptidase;11 Glia;Animals, Newborn;Peptide Fragments;Protein Isoforms;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Month = {6}, Nlm_Id = {2985190R}, Number = {6}, Organization = {University of South Florida College of Medicine, Department of Pharmacology and Therapeutics, Tampa, Florida, USA.}, Pages = {1533-41}, Pii = {JNC3144}, Pubmed = {15935069}, Title = {Altered production and proteolytic processing of brevican by transforming growth factor beta in cultured astrocytes}, Uuid = {02B8774C-6033-457A-AAFD-C3F0AE1094D0}, Volume = {93}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1471-4159.2005.03144.x}} @article{Hammond:2004, Abstract = {The migration, arrest, and ultimately positioning of cortical neurons require signaling activity from Reelin as well as from cyclin-dependent kinase 5 (Cdk5). Although both molecules control neuronal positioning, they achieve their effects by quite separate molecular pathways. Cdk5 is a serine-threonine kinase, the activity of which is dependent on its activating subunits p35 and p39. Mice deficient in Cdk5, p35, or both p35 and p39 display the hallmarks of disturbed cortical development, including cortical layer inversion, neuronal disorientation, and abnormal fiber infiltration. To distinguish between the cell- and non cell-autonomous functions of p35, we constructed p35+/+ <--> p35-/- chimeras using the lacZ gene as an independent marker for p35+/+ cells. In this shared developmental space, wild-type and mutant neurons behaved cell-autonomously with respect to layering. Wild-type cells formed a properly layered supercortex that is mirrored by an inverted mutant cortex lying underneath. However, this genotype-specific behavior was confined to the pyramidal population, and interneurons belonging to either genotype were indiscriminately distributed. However, there was also non cell-autonomous rescue of mutant neurons, and this rescue was specific only to early-born pyramidal neurons belonging to layer V. Rescued neurons reached the correct layer address and possessed appropriate neuronal morphology, orientation, and projections. Later-born neurons belonging to layers II and III were not rescued. These results demonstrate that p35 signaling can have both cell- and non cell-autonomous consequences, and their effects are not uniformly shared by cortical neurons born at different times or born at different places (projection neurons vs interneurons).}, Author = {Hammond, Vicki and Tsai, Li-Huei H. and Tan, Seong-Seng S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008;Nerve Fibers;10 Development;research support, non-u.s. gov't;Mice, Knockout;Chimera;Nerve Tissue Proteins;Pyramidal Cells;Interneurons;Animals;Cell Movement;Cerebral Cortex;Mice;Neurons}, Month = {1}, Nlm_Id = {8102140}, Number = {2}, Organization = {Howard Florey Institute, The University of Melbourne, Victoria 3010, Australia.}, Pages = {576-87}, Pii = {24/2/576}, Pubmed = {14724258}, Title = {Control of cortical neuron migration and layering: cell and non cell-autonomous effects of p35}, Uuid = {D3E1F685-40E7-47BF-A381-0339E7EBB854}, Volume = {24}, Year = {2004}, url = {papers/Hammond_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4529-03.2004}} @article{Hamo:2007, Abstract = {The potential interplay of glial cells with T cells during viral induced inflammation was assessed by comparing major histocompatibility complex molecule upregulation and retention on astrocytes and microglia. Transgenic mice expressing green fluorescent protein under control of the astrocyte-specific glial fibrillary acidic protein promoter were infected with a neurotropic coronavirus to facilitate phenotypic characterization of astrocytes and microglia using flow cytometry. Astrocytes in the adult central nervous system up-regulated class I surface expression, albeit delayed compared with microglia. Class II was barely detectable on astrocytes, in contrast to potent up-regulation on microglia. Maximal MHC expression in both glial cell types correlated with IFN-gamma levels and lymphocyte accumulation. Despite a decline of IFN-gamma concomitant to virus clearance, MHC molecule expression on glia was sustained. These data demonstrate distinct regulation of both class I and class II expression by microglia and astrocytes in vivo following viral induced inflammation. Furthermore, prolonged MHC expression subsequent to viral clearance implies a potential for ongoing presentation.}, Author = {Hamo, Ludwig and Stohlman, Stephen A. and Otto-Duessel, Maya and Bergmann, Cornelia C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Animals;Astrocytes;Encephalomyelitis;Gene Expression Regulation;Cells, Cultured;Interferon Type II;Female;Microglia;Mice, Transgenic;Genes, MHC Class I;11 Glia;Green Fluorescent Proteins;Male;Genes, MHC Class II;Flow Cytometry;research support, n.i.h., extramural;Mice;Enzyme-Linked Immunosorbent Assay;24 Pubmed search results 2008;Inflammation;Maus Elberfeld virus;Glial Fibrillary Acidic Protein}, Month = {8}, Nlm_Id = {8806785}, Number = {11}, Organization = {Department of Neuroscience, University of Southern California Keck School of Medicine, Los Angeles, California, USA.}, Pages = {1169-77}, Pubmed = {17600339}, Title = {Distinct regulation of MHC molecule expression on astrocytes and microglia during viral encephalomyelitis}, Uuid = {673F9897-E43E-4D66-9BC4-9E0C911ED42D}, Volume = {55}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20538}} @article{Hampton:2004, Abstract = {The cortical stab injury has been widely used for biochemical analysis of molecular changes following CNS injury. However, the cellular responses to this injury have not been accurately quantified. In order to provide a baseline for biochemical studies and future experiments on the manipulation of the CNS injury response we have undertaken a quantitative analysis of this injury. The proliferative and reactive responses of oligodendrocyte precursor cells, astrocytes and microglia were measured, using antibodies to NG2, glial fibrillary acidic protein (GFAP) and the cd11-b clone OX-42 to characterise these cell types at 2, 4, 7 and 14 days post-injury. Oligodendrocyte precursors and microglia proliferated rapidly during the first week, mostly within 0.3 mm of the lesion. Of the dividing cells over 60\%were oligodendrocyte precursor cells with microglia making up the balance of the dividing cells. Minimal numbers of astrocytes divided in response to the lesion. Large cells with one or two short processes that were both NG2 and OX-42 positive were identified very close to the lesion at 2 and 4 days post-lesion but not thereafter. They are likely to be blood-derived cells that express NG2 or have ingested it. NG2 immunohistochemistry and platelet-derived growth factor alpha receptor (PDGFalpha-R) in situ hybridisation on neighbouring sections was performed. In the lesioned area only 12\%of NG2 positive (+ive) cells were PDGFalpha-R +ive (a ratio of 1:8 for PDGFalpha-R +ive cells: NG2 +ive cells) compared with 33\%in the unlesioned cortex and an almost 100\%overlap in the spinal cord.}, Author = {Hampton, D. W. and Rhodes, K. E. and Zhao, C. and Franklin, R. J. M. and Fawcett, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Cell Differentiation;Glial Fibrillary Acidic Protein;Wounds, Penetrating;Comparative Study;Rats;Astrocytes;Stem Cells;Not relevant;11 Glia;Microglia;Support, Non-U.S. Gov't;Animals;Cerebral Cortex;Oligodendroglia}, Nlm_Id = {7605074}, Number = {4}, Organization = {Cambridge Centre for Brain Repair, E. D. Adrian Building, Forvie Site, Robinson Way, Cambridge CB2 2PY, UK. dhampton\@icord.org}, Pages = {813-20}, Pii = {S0306452204003719}, Pubmed = {15312894}, Title = {The responses of oligodendrocyte precursor cells, astrocytes and microglia to a cortical stab injury, in the brain}, Uuid = {5910240C-DDEE-4D0E-A055-4F084D2AD50F}, Volume = {127}, Year = {2004}, url = {papers/Hampton_Neuroscience2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2004.05.028}} @article{Hamzei-Sichani:2007, Abstract = {Gap junctions have been postulated to exist between the axons of excitatory cortical neurons based on electrophysiological, modeling, and dye-coupling data. Here, we provide ultrastructural evidence for axoaxonic gap junctions in dentate granule cells. Using combined confocal laser scanning microscopy, thin-section transmission electron microscopy, and grid-mapped freeze-fracture replica immunogold labeling, 10 close appositions revealing axoaxonic gap junctions ( approximately 30-70 nm in diameter) were found between pairs of mossy fiber axons ( approximately 100-200 nm in diameter) in the stratum lucidum of the CA3b field of the rat ventral hippocampus, and one axonal gap junction ( approximately 100 connexons) was found on a mossy fiber axon in the CA3c field of the rat dorsal hippocampus. Immunogold labeling with two sizes of gold beads revealed that connexin36 was present in that axonal gap junction. These ultrastructural data support computer modeling and in vitro electrophysiological data suggesting that axoaxonic gap junctions play an important role in the generation of very fast (>70 Hz) network oscillations and in the hypersynchronous electrical activity of epilepsy.}, Author = {Hamzei-Sichani, Farid and Kamasawa, Naomi and Janssen, William G. M. and Yasumura, Thomas and Davidson, Kimberly G. V. and Hof, Patrick R. and Wearne, Susan L. and Stewart, Mark G. and Young, Steven R. and Whittington, Miles A. and Rash, John E. and Traub, Roger D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Gap Junctions;Microtomy;research support, non-u.s. gov't;Rats, Sprague-Dawley;21 Neurophysiology;Mossy Fibers, Hippocampal;Gold;Freeze Fracturing;Rats;21 Gap junctions;research support, n.i.h., extramural;Microscopy, Immunoelectron;Animals;24 Pubmed search results 2008;Microscopy, Electron, Transmission}, Month = {7}, Nlm_Id = {7505876}, Number = {30}, Organization = {Program in Neural and Behavioral Science, State University of New York, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, NY 11203, USA. fh81\@alumni-mail.gs.columbia.edu}, Pages = {12548-53}, Pii = {0705281104}, Pubmed = {17640909}, Title = {Gap junctions on hippocampal mossy fiber axons demonstrated by thin-section electron microscopy and freeze fracture replica immunogold labeling}, Uuid = {9BABEA0A-0DD2-4038-AA43-A2E978BFD4AA}, Volume = {104}, Year = {2007}, url = {papers/Hamzei-Sichani_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0705281104}} @article{Han:2007a, Abstract = {Sensory experience can reorganize cortical sensory representations in an epoch of early development. During this period, cortical sensory neurons may shift their response selectivity and become tuned to more frequently occurring stimuli. Although this enlarged cortical representation is believed to underlie improved sensory processing of the experienced stimuli, its precise perceptual consequences are still unknown. We show that rearing rats in a single-frequency tonal environment results in enlarged cortical representations of the frequencies near that of the experienced tone, but the animals are impaired in perceptual discrimination of the over-represented frequencies. By contrast, discrimination of the neighboring under-represented frequencies is substantially improved. Computational analysis indicated that the altered perceptual ability could be fully accounted for by the sound exposure-induced reorganization of cortical primary auditory representations. These results indicate that early experience shapes sensory perception. The same plasticity processes may be important in optimizing phonemic representations in humans.}, Author = {Han, Yoon K. and K{\"o}ver, Hania and Insanally, Michele N. and Semerdjian, John H. and Bao, Shaowen}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Helen Wills Neuroscience Institute, 210X Barker Hall, University of California, Berkeley, California 94720, USA.}, Pages = {1191-7}, Pii = {nn1941}, Pubmed = {17660815}, Title = {Early experience impairs perceptual discrimination}, Uuid = {BEACA69C-0AFB-4047-B869-1A397BD1A5F7}, Volume = {10}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1941}} @article{Han:2007, Abstract = {Competition between neurons is necessary for refining neural circuits during development and may be important for selecting the neurons that participate in encoding memories in the adult brain. To examine neuronal competition during memory formation, we conducted experiments with mice in which we manipulated the function of CREB (adenosine 3',5'-monophosphate response element-binding protein) in subsets of neurons. Changes in CREB function influenced the probability that individual lateral amygdala neurons were recruited into a fear memory trace. Our results suggest a competitive model underlying memory formation, in which eligible neurons are selected to participate in amemorytrace as a function of their relative CREB activity at the time of learning.}, Author = {Han, Jin-Hee H. and Kushner, Steven A. and Yiu, Adelaide P. and Cole, Christy J. and Matynia, Anna and Brown, Robert A. and Neve, Rachael L. and Guzowski, John F. and Silva, Alcino J. and Josselyn, Sheena A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Transcription, Genetic;10 Development;Animals;Fear;Memory;Conditioning (Psychology);Neuronal Plasticity;Amygdala;research support, non-u.s. gov't;10 circuit formation;Genetic Vectors;Cyclic AMP Response Element-Binding Protein;21 Neurophysiology;Neurons;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Cytoskeletal Proteins}, Month = {4}, Nlm_Id = {0404511}, Number = {5823}, Organization = {Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8, Canada.}, Pages = {457-60}, Pii = {316/5823/457}, Pubmed = {17446403}, Title = {Neuronal competition and selection during memory formation}, Uuid = {2D0F1D67-86C9-466E-B844-641536AC62E1}, Volume = {316}, Year = {2007}, url = {papers/Han_Science2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1139438}} @article{Hanashima:2006, Abstract = {Innervation of the neocortex by the thalamus is dependent on the precise coordination of spatial and temporal guidance cues. In this issue of Cell, work by L{\'o}pez-Bendito et al.(2006) reveals that tangentially migrating cells within the ventral telencephalon are essential for axonal navigation between the thalamus and the neocortex, a process apparently mediated by Neuregulin-1/ErbB4 short- and long-range signaling.}, Author = {Hanashima, Carina and Moln{\'a}r, Zolt{\'a}n and Fishell, Gord}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008;Neuregulin-1;Receptor, Epidermal Growth Factor;21 Neurophysiology;Signal Transduction;comment;Animals;Cell Movement;Cerebral Cortex;Thalamus;Axons}, Month = {4}, Nlm_Id = {0413066}, Number = {1}, Organization = {Developmental Genetics Program and the Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA.}, Pages = {24-7}, Pii = {S0092-8674(06)00368-0}, Pubmed = {16615886}, Title = {Building bridges to the cortex}, Uuid = {AE657FD6-B569-4FFA-A5C9-7AE3DA4BB6FF}, Volume = {125}, Year = {2006}, url = {papers/Hanashima_Cell2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.03.021}} @article{Hanashima:2004, Abstract = {During mammalian cerebral corticogenesis, progenitor cells become progressively restricted in the types of neurons they can produce. The molecular mechanism that determines earlier versus later born neuron fate is unknown. We demonstrate here that the generation of the earliest born neurons, the Cajal-Retzius cells, is suppressed by the telencephalic transcription factor Foxg1. In Foxg1 null mutants, we observed an excess of Cajal-Retzius neuron production in the cortex. By conditionally inactivating Foxg1 in cortical progenitors that normally produce deep-layer cortical neurons, we demonstrate that Foxg1 is constitutively required to suppress Cajal-Retzius cell fate. Hence, the competence to generate the earliest born neurons during later cortical development is actively suppressed but not lost. 1095-9203 Journal Article}, Author = {Hanashima, C. and Li, S. C. and Shen, L. and Lai, E. and Fishell, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {Science}, Keywords = {10 Development;F pdf}, Number = {5654}, Organization = {Developmental Genetics Program and the Department of Cell Biology, The Skirball Institute of Biomolecular Medicine, New York University Medical Center, 540 First Avenue, New York, NY 10016, USA.}, Pages = {56-9}, Pubmed = {14704420}, Title = {Foxg1 suppresses early cortical cell fate}, Uuid = {1EF583E7-865C-47A7-9F87-D073DE1EE1E6}, Volume = {303}, Year = {2004}, url = {papers/Hanashima_Science2004.pdf}} @article{Hanazono:2002, Abstract = {BACKGROUND: The green fluorescent protein (GFP) has proven a useful marker in retroviral gene transfer studies targeting hematopoietic stem cells (HSCs) in mice. However, several investigators have reported very low in vivo peripheral blood marking levels in nonhuman primates after transplantation of HSCs transduced with the GFP gene. We retrovirally marked cynomolgus monkey HSCs with the GFP gene, and tracked in vivo marking levels within both bone marrow progenitor cells and mature peripheral blood cells following autologous transplantation after myeloablative conditioning. METHODS: Bone marrow cells were harvested from three cynomolgus macaques and enriched for the primitive fraction by CD34 selection. CD34(+) cells were transduced with one of three retroviral vectors all expressing the GFP gene and were infused after myeloablative total body irradiation (500 cGy x 2). Following transplantation, proviral levels and fluorescence were monitored among clonogenic bone marrow progenitors and mature peripheral blood cells. RESULTS: Although 13-37\%of transduced cells contained the GFP provirus and 11-13\%fluoresced ex vivo, both provirus and fluorescence became almost undetectable in the peripheral blood within several months after transplantation regardless of the vectors used. However, on sampling of bone marrow at multiple time points, significant fractions (5-10\%) of clonogenic progenitors contained the provirus and fluoresced ex vivo reflecting a significant discrepancy between GFP gene marking levels within bone marrow cells and their mature peripheral blood progeny. The discrepancy (at least one log) persisted for more than 1 year after transplantation. Since no cytotoxic T lymphocytes against GFP were detected in the animals, an immune response against GFP is an unlikely explanation for the low levels of transduced peripheral blood cells. Administration of granulocyte colony stimulating factor and stem cell factor resulted in mobilization of transduced bone marrow cells detectable as mature granulocyte progeny which expressed the GFP gene, suggesting that transduced progenitor cells in bone marrow could be mobilized into the peripheral blood and differentiated into granulocytes. CONCLUSIONS: Low levels of GFP-transduced mature cells in the peripheral blood of nonhuman primates may reflect a block to differentiation associated with GFP; this block can be overcome in part by nonphysiological cytokine treatment ex vivo and in vivo.}, Author = {Hanazono, Yutaka and Terao, Keiji and Shibata, Hiroaki and Nagashima, Takeyuki and Ageyama, Naohide and Asano, Takayuki and Ueda, Yasuji and Kato, Ikunoshin and Kume, Akihiro and Hasegawa, Mamoru and Ozawa, Keiya}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1099-498X}, Journal = {J Gene Med}, Keywords = {Gene Transfer Techniques;Research Support, Non-U.S. Gov't;Luminescent Proteins;Hematopoietic Stem Cells;Transduction, Genetic;Macaca fascicularis;11 Glia;Green Fluorescent Proteins;Male;Animals;Leukocytes, Mononuclear}, Medline = {22209487}, Nlm_Id = {9815764}, Number = {5}, Organization = {Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan. hanazono\@jichi.ac.jp}, Pages = {470-7}, Pubmed = {12221639}, Title = {Introduction of the green fluorescent protein gene into hematopoietic stem cells results in prolonged discrepancy of in vivo transduction levels between bone marrow progenitors and peripheral blood cells in nonhuman primates}, Uuid = {5EB26562-BC92-4A2D-8D46-4F2CAA4FEFD5}, Volume = {4}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jgm.307}} @article{Hand:2005, Abstract = {The molecular mechanisms specifying the dendritic morphology of different neuronal subtypes are poorly understood. Here we demonstrate that the bHLH transcription factor Neurogenin2 (Ngn2) is both necessary and sufficient for specifying the dendritic morphology of pyramidal neurons in vivo by specifying the polarity of its leading process during the initiation of radial migration. The ability of Ngn2 to promote a polarized leading process outgrowth requires the phosphorylation of a single tyrosine residue at position 241, an event that is neither involved in Ngn2 direct transactivation properties nor its proneural function. Interestingly, the migration defect observed in the Ngn2 knockout mouse and in progenitors expressing the Ngn2(Y241F) mutation can be rescued by inhibiting the activity of the small-GTPase RhoA in cortical progenitors. Our results demonstrate that Ngn2 coordinates the acquisition of the radial migration properties and the unipolar dendritic morphology characterizing pyramidal neurons through molecular mechanisms distinct from those mediating its proneural activity.}, Author = {Hand, Randal and Bortone, Dante and Mattar, Pierre and Nguyen, Laurent and Heng, Julian Ik-Tsen and Guerrier, Sabrice and Boutt, Elizabeth and Peters, Eldon and Barnes, Anthony P. and Parras, Carlos and Schuurmans, Carol and Guillemot, Fran\c{c}ois and Polleux, Franck}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Research Support, N.I.H., Extramural;24 Pubmed search results 2008;Green Fluorescent Proteins;Male;Animals;Cells, Cultured;Age Factors;Sequence Alignment;rhoA GTP-Binding Protein;Research Support, U.S. Gov't, P.H.S.;Cell Movement;In Vitro;Gene Expression Regulation, Developmental;Cell Count;Pregnancy;Electrophoresis, Gel, Pulsed-Field;Basic Helix-Loop-Helix Transcription Factors;Microtubule-Associated Proteins;Tubulin;Neocortex;Dendrites;Pyramidal Cells;Comparative Study;Blotting, Western;Electroporation;Fluorescent Antibody Technique;Time Factors;Cloning, Molecular;Female;Embryo;Chickens;Stem Cells;Microscopy, Confocal;Mice;Models, Biological;Phosphorylation;Humans;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't;Tyrosine}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Phamacology, Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA.}, Pages = {45-62}, Pii = {S0896-6273(05)00736-1}, Pubmed = {16202708}, Title = {Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex}, Uuid = {700AF376-B093-44DB-9CE1-F4E52B860725}, Volume = {48}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.08.032}} @article{Hanganu:2001, Abstract = {Subplate neurons play an important role in early cortical development. To investigate whether these transient neurons receive synaptic inputs, we performed whole-cell recordings from visually identified and biocytin-labeled subplate cells in somatosensory cortical slices from postnatal day 0-3 rats. Subplate neurons had an average resting membrane potential of -55 mV and input resistance of approximately 1.1 G ohms. Suprathreshold current injection elicited in 67\%of the cells repetitive action potentials at 4-13 Hz and the remaining 33\%showed only one spike. Three classes of spontaneous postsynaptic currents (sPSCs) could be identified: (i) Fast sPSCs, with an average amplitude of 14 pA and a decay time of 6.3 ms, which showed a 95\%decrease in their frequency during (+/-)-gamma-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate receptor blockade. Cyclothiazide caused a 3.5-fold increase in the decay time, indicating that fast sPSCs were mediated by AMPA receptors. (ii) Slow sPSCs, with 18 pA amplitude and 51.2 ms decay time were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist CPP. (iii) Chloride-driven sPSCs, with 34.4 pA amplitude and 123 ms decay time that were blocked by the gamma-amino-butyric acid A (GABA(A)) receptor antagonist gabazine. While tetrodotoxin citrate (TTX) blocked completely NMDA-mediated slow sPSCs, the frequency of AMPA- and GABA(A)-mediated sPSCs was reduced in TTX by 55 and 90\%, respectively. These results indicate that subplate neurons receive functional synaptic inputs mediated by AMPA, NMDA and GABA(A) receptors.}, Author = {Hanganu, I. L. and Kilb, W. and Luhmann, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-28 17:14:28 +0000}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Electrophysiology;Animals;Synapses;Rats;Patch-Clamp Techniques;in vitro ;Receptors, AMPA;Rats, Wistar;Tetrodotoxin;Male;research support, non-u.s. gov't ;Animals, Newborn;Receptors, GABA-A;21 Neurophysiology;Neurons;Somatosensory Cortex;21 Activity-development;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Biotin;Excitatory Postsynaptic Potentials; in vitro}, Month = {5}, Nlm_Id = {9110718}, Number = {5}, Organization = {Institute of Neurophysiology, Heinrich-Heine-University, D{\"u}sseldorf, Germany.}, Pages = {400-10}, Pubmed = {11313292}, Title = {Spontaneous synaptic activity of subplate neurons in neonatal rat somatosensory cortex}, Uuid = {E26A62C6-483B-451A-8139-4E110AB7A3B7}, Volume = {11}, Year = {2001}, url = {papers/Hanganu_CerebCortex2001.pdf}} @article{Hanganu:2004, Abstract = {The establishment of cortical synaptic circuits during early development requires the presence of subplate neurons (SPn's), a heterogeneous population of neurons capable to integrate and process synaptic information from the thalamus, cortical plate, and neighboring SPn's. An accumulation of cholinergic afferents and nicotinic acetylcholine receptors (nAChRs) has been documentated in the subplate around birth. To assess the developmental role of the cholinergic innervation onto SPn's, we used whole cell patch-clamp recordings of visually identified and biocytin-labeled SPn's in neonatal rat somatosensory cortex. Functional nAChRs were present in 92\%of the investigated SPn's. Activation of postsynaptic nAChRs by local application of agonists elicited a brief membrane depolarization associated with a barrage of action potentials and large inward currents reversing around 0 mV. According to our pharmacological data, excitation of SPn's is mediated by alpha4beta2 receptors. In contrast, functional alpha7 nAChRs could not be identified on SPn's. Activation of nAChRs affected neither the spontaneous synaptic activity of SPn's nor the synaptic connections between thalamus and SPn's and within subplate. Nicotine, at concentrations reaching the developing brain by maternal smoking, induced a severe desensitization of nAChRs and an increase in the baseline noise. These results indicate that nAChR-mediated excitation of SPn's may stabilize the developing synaptic circuits and suggest the involvement of nAChRs located on SPn's in the fetal tobacco syndrome.}, Author = {Hanganu, Ileana L. and Luhmann, Heiko J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Receptors, Nicotinic;21 Neurophysiology;Action Potentials;Rats;Nicotine;research support, non-u.s. gov't ;Dose-Response Relationship, Drug;21 Activity-development;Rats, Wistar;in vitro ;Somatosensory Cortex;Animals;comparative study ;24 Pubmed search results 2008;Carbachol;Neurons}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Institute of Physiology and Pathophysiology, Johannes-Gutenberg University, Duesbergweg 6, D-55128 Mainz, Germany. hanganu\@uni-mainz.de}, Pages = {189-98}, Pii = {00010.2004}, Pubmed = {14999055}, Title = {Functional nicotinic acetylcholine receptors on subplate neurons in neonatal rat somatosensory cortex}, Uuid = {6AB6B46B-9EA4-4777-B284-3D2690EF75AC}, Volume = {92}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00010.2004}} @article{Hanganu:2002, Abstract = {Subplate neurons (SPn) play an important role in the formation of thalamocortical connections during early development and show glutamatergic and GABAergic spontaneous synaptic activity. We characterized these synaptic inputs by performing whole-cell recordings from SPn in somatosensory cortical slices of postnatal day 0-3 rats. At -70 mV, electrical stimulation of the thalamocortical afferents elicited in 68\%of the SPn a monosynaptic CNQX-sensitive postsynaptic current (PSC). These fast PSCs were mediated by AMPA receptors, because they were prolonged by cyclothiazide and blocked by GYKI 52466. On membrane depolarization, thalamocortical stimulation elicited in 50\%of the cells an additional slow monosynaptic component mediated by NMDA receptors. Stimulation of the cortical plate evoked in 72\%of SPn a monosynaptic AMPA receptor-mediated PSC with an additional NMDA component at depolarized membrane potentials and in 40\%of the investigated cells polysynaptic responses, depending on GABA(A) and NMDA receptors. Stimulation of the subplate elicited in 67\%of SPn a monosynaptic dual-component PSC mediated by AMPA and NMDA receptors activated at -70 mV and in 12\%of SPn a monosynaptic single-component PSC mediated by AMPA receptors with an additional NMDA component activated at depolarized membrane potentials. A monosynaptic GABAergic response could be observed in 68\%of SPn after stimulation of the subplate. In gramicidin-perforated patch recordings, bath application of GABA caused membrane depolarization to -40 mV and elicited action potentials. These results demonstrate that SPn receive distinct functional synaptic inputs arising from the thalamus, cortical plate, and subplate, indicating that SPn are capable of integrating and processing information from cortical and subcortical regions.}, Author = {Hanganu, Ileana L. and Kilb, Werner and Luhmann, Heiko J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-28 17:16:09 +0000}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;gamma-Aminobutyric Acid;Electric Stimulation;Lysine;Synapses;Animals;Rats;Afferent Pathways;Patch-Clamp Techniques;Cell Membrane;in vitro ;Receptors, AMPA;Rats, Wistar;Male;research support, non-u.s. gov't ;Animals, Newborn;Action Potentials;Receptors, GABA-A;Thalamus;21 Neurophysiology;Neurons;Membrane Potentials;Somatosensory Cortex;21 Activity-development;GABA Antagonists;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials; in vitro}, Month = {8}, Nlm_Id = {8102140}, Number = {16}, Organization = {Institute of Neurophysiology, Heinrich-Heine-University D{\"u}sseldorf, D-40001 D{\"u}sseldorf, Germany.}, Pages = {7165-76}, Pii = {22/16/7165}, Pubmed = {12177212}, Title = {Functional synaptic projections onto subplate neurons in neonatal rat somatosensory cortex}, Uuid = {32458FFD-2940-4855-A354-F69C74EC6D5F}, Volume = {22}, Year = {2002}, url = {papers/Hanganu_JNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/20026716}} @article{Hanganu:2006, Abstract = {During visual system development, the light-insensitive retina spontaneously generates waves of activity, which are transmitted to the lateral geniculate nucleus. The crucial question is whether retinal waves are further transmitted to the cortex and influence the early cortical patterns of activity. Using simultaneous recordings from the rat retina and visual cortex during the first postnatal week in vivo, we found that spontaneous retinal bursts are correlated with spindle bursts (intermittent network bursts associated with spindle-shape field oscillations) in the contralateral visual cortex (V1). V1 spindle bursts could be evoked by electrical stimulation of the optic nerve. Intraocular injection of forskolin, which augments retinal waves, increased the occurrence of V1 spindle bursts. Blocking propagation of retinal activity, or removal of the retina reduced the frequency, but did not completely eliminate the cortical spindle bursts. These results indicate that spontaneous retinal waves are transmitted to the visual cortex and trigger endogenous spindle bursts. We propose that the interaction between retinal waves and spindle bursts contributes to the development of visual pathways to the cortex.}, Author = {Hanganu, Ileana L. and Ben-Ari, Yehezkel and Khazipov, Rustem}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-05-24 02:40:23 +0000}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Retina;Electric Stimulation;Animals;Rats;Functional Laterality;Patch-Clamp Techniques;Visual Pathways;comparative study ;Tetrodotoxin;research support, non-u.s. gov't ;Animals, Newborn;Action Potentials;21 Neurophysiology;Anesthetics, Local;Forskolin;21 Activity-development;24 Pubmed search results 2008;21 Cortical oscillations;Visual Cortex;Excitatory Postsynaptic Potentials; currOpinRvw}, Month = {6}, Nlm_Id = {8102140}, Number = {25}, Organization = {Institut de Neurobiologie de la Mediteran{\'e}e, Universit{\'e} de la Mediteran{\'e}e, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U29, 13273 Marseille, France.}, Pages = {6728-36}, Pii = {26/25/6728}, Pubmed = {16793880}, Title = {Retinal waves trigger spindle bursts in the neonatal rat visual cortex}, Uuid = {71C74001-527B-4E5B-A0B2-6ED03756FB93}, Volume = {26}, Year = {2006}, url = {papers/Hanganu_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0752-06.2006}} @article{Hanisch:2007, Abstract = {Microglial cells constitute the resident macrophage population of the CNS. Recent in vivo studies have shown that microglia carry out active tissue scanning, which challenges the traditional notion of 'resting' microglia in the normal brain. Transformation of microglia to reactive states in response to pathology has been known for decades as microglial activation, but seems to be more diverse and dynamic than ever anticipated--in both transcriptional and nontranscriptional features and functional consequences. This may help to explain why engagement of microglia can be either neuroprotective or neurotoxic, resulting in containment or aggravation of disease progression. Moreover, little is known about the heterogeneity of microglial responses in different pathologic contexts that results from regional adaptations or from the progression of a disease. In this review, we focus on several key observations that illustrate the multi-faceted activities of microglia in the normal and pathologic brain.}, Author = {Hanisch, Uwe-Karsten K. and Kettenmann, Helmut}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {9809671}, Number = {11}, Organization = {Institute of Neuropathology, University of G{\"o}ttingen, D-37075 G{\"o}ttingen, Germany.}, Pages = {1387-94}, Pii = {nn1997}, Pubmed = {17965659}, Title = {Microglia: active sensor and versatile effector cells in the normal and pathologic brain}, Uuid = {E6494B99-8A79-40FE-B215-0B4BA46890BE}, Volume = {10}, Year = {2007}, url = {papers/Hanisch_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1997}} @article{Hanna:1973, Author = {Hanna, G. R. and Stalmaster, R. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {Epilepsy;24 Pubmed search results 2008;Electroencephalography;21 Epilepsy;21 Neurophysiology;Nerve Degeneration;Cats;Motor Cortex;Animals;Disease Models, Animal;Cerebral Cortex;Freezing;Electrodes, Implanted}, Medline = {73238377}, Month = {9}, Nlm_Id = {0401060}, Number = {9}, Pages = {918-25}, Pubmed = {4737684}, Title = {Cortical epileptic lesions produced by freezing}, Uuid = {0988714F-434B-42EE-AE2E-AD50A0B45824}, Volume = {23}, Year = {1973}} @article{Hannan:1999, Abstract = {Neuronal heterotopia are seen in various pathologies and are associated with intractable epilepsy. We examined brain tissue from four children with subcortical or periventricular nodular heterotopia of different aetiologies: one with severe epilepsy following focal brain trauma at 17 weeks gestation, one with hemimegalencephaly and intractable epilepsy, one with focal cortical dysplasia and intractable epilepsy, and one dysmorphic term infant with associated hydrocephalus and polymicrogyria. The connectivity of nodules was investigated using histological and carbocyanine dye (DiI) tracing techniques. DiI crystal placement adjacent to heterotopic nodules revealed numerous DiI-labelled fibres within a 2-3 mm radius of the crystals. Although we observed labelled fibres closely surrounding nodules, the majority did not penetrate them. Placement of DiI crystals within nodules also identified a limited number of projections out of the nodules and in one case there was evidence for connectivity between adjacent nodules. The cellular and neurochemical composition of nodules was also examined using immunohistochemistry for calretinin and neuropeptide Y (NPY), which are normally expressed in GABAergic cortical interneurons. Within heterotopic nodules from all cases, numerous calretinin-positive neurons were identified, along with a few cell bodies and many processes positive for NPY. Calretinin-positive neurons within nodules were less morphologically complex than those in the cortex, which may reflect incomplete differentiation into an inhibitory neuronal phenotype. There were also abnormal clusters of calretinin-positive cells in the overlying cortical plate, indicating that the migratory defect which produces heterotopic nodules also affects development of the cortex itself. Thus, heterotopic nodules consisting of multiple neuronal cell types are associated with malformation in the overlying cortical plate, and have limited connectivity with other brain regions. This abnormal development of connectivity may affect neuronal maturation and consequently the balance of excitation and inhibition in neuronal circuits, leading to their epileptogenic potential.}, Author = {Hannan, A. J. and Servotte, S. and Katsnelson, A. and Sisodiya, S. and Blakemore, C. and Squier, M. and Moln{\'a}r, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0006-8950}, Journal = {Brain}, Keywords = {Fatal Outcome;10 Development;case reports;Magnetic Resonance Imaging;Fluorescent Dyes;Humans;gamma-Aminobutyric Acid;Fluorescent Antibody Technique;Female;Epilepsy;Child;research support, non-u.s. gov't;Calcium-Binding Protein, Vitamin D-Dependent;Male;Neuropeptide Y;Brain Chemistry;Cerebral Cortex;Cell Size;10 genetics malformation;Carbocyanines;Infant, Newborn;24 Pubmed search results 2008;Interneurons;Choristoma}, Month = {2}, Nlm_Id = {0372537}, Organization = {University Laboratory of Physiology, University of Oxford, UK.}, Pages = {219-38}, Pubmed = {10071051}, Title = {Characterization of nodular neuronal heterotopia in children}, Uuid = {5E805D44-FFAB-493A-A39C-95B2279D7D07}, Volume = {122 ( Pt 2)}, Year = {1999}} @article{Hannon:2002, Abstract = {A conserved biological response to double-stranded RNA, known variously as RNA interference (RNAi) or post-transcriptional gene silencing, mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes. RNAi has been cultivated as a means to manipulate gene expression experimentally and to probe gene function on a whole-genome scale. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Hannon, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:48 -0400}, Journal = {Nature}, Keywords = {RNA, Double-Stranded/chemistry/genetics/*metabolism;T pdf;*Gene Silencing;Genetic Techniques;Genome;Support, U.S. Gov't, Non-P.H.S.;RNA Processing, Post-Transcriptional;Models, Genetic;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't;23 Technique}, Number = {6894}, Organization = {Cold Spring Harbour Laboratory, New York 11724, USA. hannon\@cshl.org}, Pages = {244-51}, Title = {RNA interference}, Uuid = {C001D54E-371B-44E4-BB82-FE4A2A93F214}, Volume = {418}, Year = {2002}, url = {papers/Hannon_Nature2002.pdf}} @article{Hansen:2000, Abstract = {A pathogenetic hallmark of retroviral neurodegeneration is the affinity of neurovirulent retroviruses for microglia cells, while degenerating neurons are excluded from retroviral infections. Microglia isolated ex vivo from rats peripherally infected with a neurovirulent retrovirus released abundant mature type C virions; however, infectivity associated with microglia was very low. In microglia, viral transcription was unaffected but envelope proteins were insufficiently cleaved into mature viral proteins and were not detected on the microglia cell surface. These microglia-specific defects in envelope protein translocation and processing not only may have prevented formation of infectious virus particles but also may have caused further cellular defects in microglia with the consequence of indirect neuronal damage. It is conceivable that similar events play a role in neuro-AIDS.}, Author = {Hansen, R. and Czub, S. and Werder, E. and Herold, J. and Gosztonyi, G. and Gelderblom, H. and Schimmer, S. and Mazgareanu, S. and ter Meulen, V. and Czub, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Macrophages, Peritoneal;Animals;Cells, Cultured;Rats;Microglia;Cell Membrane;Virion;Not relevant;11 Glia;Leukemia Virus, Murine;Intracellular Fluid;Defective Viruses;Viral Envelope Proteins;Support, Non-U.S. Gov't;Rats, Inbred F344;Protein Processing, Post-Translational;Mice;Retroviridae Proteins, Oncogenic;Transcription, Genetic}, Medline = {20111297}, Month = {2}, Nlm_Id = {0113724}, Number = {4}, Organization = {Institut f]ur Virologie und Immunbiologie, Universit]at W]urzburg, D-97078 W]urzburg, Germany.}, Pages = {1775-80}, Pubmed = {10644349}, Title = {Abundant defective viral particles budding from microglia in the course of retroviral spongiform encephalopathy}, Uuid = {864ACFA8-C8FF-43DB-B4D3-ABDDE5924265}, Volume = {74}, Year = {2000}, url = {papers/Hansen_JVirol2000.pdf}} @article{Hanson:2004, Abstract = {Rhythmic spontaneous electrical activity occurs in many parts of the developing nervous system, where it plays essential roles in the refinement of neural connections. By blocking or slowing this bursting activity, via in ovo drug applications at precise developmental periods, we show that such activity is also required at much earlier stages for spinal motoneurons to accurately execute their first major dorsal-ventral pathfinding decision. Blockade or slowing of rhythmic bursting activity also prevents the normal expression patterns of EphA4 and polysialic acid on NCAM, which may contribute to the pathfinding errors observed. More prolonged (E2-5) blockade resulted in a downregulation of LIM homeodomain transcription factors, but since this occurred only after the pathfinding errors and alterations in guidance molecules, it cannot have contributed to them.}, Author = {Hanson, M. Gartz and Landmesser, Lynn T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cell Differentiation;Animals;Gene Expression Regulation, Developmental;Homeodomain Proteins;Cell Membrane;Cell Movement;Nerve Growth Factors;Spinal Cord;Research Support, U.S. Gov't, P.H.S.;Receptor, EphA4;Action Potentials;Chick Embryo;Muscle, Skeletal;21 Neurophysiology;Sialic Acids;Down-Regulation;Receptors, Glycine;GABA Antagonists;Motor Neurons;24 Pubmed search results 2008;Growth Cones;Neural Inhibition;Neural Cell Adhesion Molecules; 21 Activity-development}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Neurosciences, Case School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.}, Pages = {687-701}, Pii = {S0896627304005239}, Pubmed = {15339650}, Title = {Normal patterns of spontaneous activity are required for correct motor axon guidance and the expression of specific guidance molecules}, Uuid = {DB541A62-F574-4675-B09B-0C806293614F}, Volume = {43}, Year = {2004}, url = {papers/Hanson_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.08.018}} @article{Hao:1995, Abstract = {Gene therapy is a potential treatment for hemophilia, wherein cells transduced with a normal factor IX gene could provide a continuous in vivo source of circulating factor IX. In this study, we examined the potential use of hematopoietic cells as a target for factor IX gene therapy. Human myeloid leukemia cells (HL-60) were transduced by retroviral vectors carrying a normal human factor IX cDNA under control of either the Moloney murine leukemia virus long terminal repeat (MoMuLV LTR) (LIXSN), the SV40 promoter (LNSVIX), or a cytomegalovirus (CMV) promoter (LNCIX). Factor IX production was measured in the transduced cells both in the uninduced state and after induction of granulocytic differentiation [with dimethylsulfoxide (DMSO)] or monocytoid differentiation [with phorbol myristic acetate (PMA)]. Transcription of factor IX from the MoMuLV LTR was seen in all cells, with a two-fold increase upon differentiation. Induction with PMA led to an 8- to 15-fold increase in factor IX transcripts from an internal CMV promoter. No factor IX transcripts from the internal SV40 promoter were detected. Immunoreactive factor IX protein was identified by Western blot from induced HL-60 cells transduced by either LIXSN or LNCIX. Factor IX production by HL-60 cells transduced by LNCIX ranged from 38-93 ng/10(6) cells/24 hr following induction of monocytic differentiation. The factor IX antigen titer was directly related to factor IX coagulant titer (r = 0.98; p <0.001). These data indicate that human myelomonocytic cells are capable of performing the necessary post-translational modifications to produce functional factor IX.(ABSTRACT TRUNCATED AT 250 WORDS) 1043-0342 Journal Article}, Author = {Hao, Q. L. and Malik, P. and Salazar, R. and Tang, H. and Gordon, E. M. and Kohn, D. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Hum Gene Ther}, Keywords = {Retroviridae/*genetics;*Genetic Vectors;Coagulants/metabolism;Tetradecanoylphorbol Acetate/pharmacology;EE, DMSO, abstr;Human;08 Aberrant cell cycle;Hematopoietic System/metabolism;Blotting, Northern;HL-60 Cells;Factor IX/biosynthesis/*genetics/immunology;Support, Non-U.S. Gov't;*Gene Transfer Techniques}, Number = {7}, Organization = {Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital Los Angeles, CA, USA.}, Pages = {873-80}, Pubmed = {7578406}, Title = {Expression of biologically active human factor IX in human hematopoietic cells after retroviral vector-mediated gene transduction}, Uuid = {D0803E1F-5451-4AB3-813A-D65DDE720CC5}, Volume = {6}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7578406}} @article{Hardiman:1988, Abstract = {Fifty patients underwent superficial temporal lobectomy for intractable temporal lobe epilepsy. Total cure rate was 52\%, and significant improvement was achieved in 88\%. Cytoarchitectural changes in gray and white tissue were analyzed under light microscopy. Neuronal dysgenesis was correlated with the duration of seizure disorder, age of onset, and other etiologic factors, and with clinical outcome. Temporal lobes from 33 neurologically normal autopsy brains which were age- and sex-matched with patients were examined as controls. Severe neuronal ectopia (greater than 8 neurons/2 mm2 white matter) was present in 42\%of patients with epilepsy and in none of controls. There was neuronal clustering in 28\%of those with epilepsy, and Chaslin's (subpial) gliosis in 38\%. Controls did not have these changes. The presence of severe neuronal ectopia and clustering was predictive of a favorable clinical outcome following surgery (p less than 0.05). No correlation was found between microdysgenesis and other factors. These findings suggest that the presence of neuronal dysgenesis may be of significance in the clinical outcome following surgery, and that the abnormal tissue may be important as a morphologic substrate for seizures in some patients.}, Author = {Hardiman, O. and Burke, T. and Phillips, J. and Murphy, S. and O'Moore, B. and Staunton, H. and Farrell, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {Reference Values;10 Development;21 Dysplasia-heterotopia;21 Neurophysiology;Adolescent;Adult;Epilepsy, Temporal Lobe;Female;Middle Aged;10 genetics malformation;Child;Humans;Male;Temporal Lobe;Neurons;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {0401060}, Number = {7}, Organization = {Richmond Institute of Neurology and Neurosurgery, Beaumont Hospital, Dublin, Ireland.}, Pages = {1041-7}, Pubmed = {3386820}, Title = {Microdysgenesis in resected temporal neocortex: incidence and clinical significance in focal epilepsy}, Uuid = {D4D5B7B9-4E8D-4600-80EC-6AF2216017D8}, Volume = {38}, Year = {1988}} @article{Harkany:2004, Abstract = {Embryonic stem (ES) cells are multipotent progenitors with unlimited developmental potential, and in vitro differentiated ES cell-derived neuronal progenitors can develop into functional neurons when transplanted in the central nervous system. As the capacity of naive primary ES cells to integrate in the adult brain and the role of host neural tissue therein are yet largely unknown, we grafted low densities of undifferentiated mouse ES (mES) cells in adult mouse brain regions associated with neurodegenerative disorders; and we demonstrate that ES cell-derived neurons undergo gradual integration in recipient tissue and acquire morphological and electrophysiological properties indistinguishable from those of host neurons. Only some brain areas permitted survival of mES-derived neural progenitors and formed instructive environments for neuronal differentiation and functional integration of naive mES cells. Hence, region-specific presence of microenvironmental cues and their pivotal involvement in controlling ES cell integration in adult brain stress the importance of recipient tissue characteristics in formulating cell replacement strategies for neurodegenerative disorders.}, Author = {Harkany, Tibor and And{\"a}ng, Michael and Kingma, Hylke Jan and G{\"o}rcs, Tam{\'a}s J. and Holmgren, Carl D. and Zilberter, Yuri and Ernfors, Patrik}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Cell Survival;Cell Differentiation;Electrophysiology;Animals;Cells, Cultured;Stem Cell Transplantation;Brain;Patch-Clamp Techniques;Mice, Transgenic;Mice, Inbred C57BL;Green Fluorescent Proteins;Male;17 Transplant Regeneration;Neurons;Mice;Luminescent Proteins;Stem Cells;22 Stem cells;Graft Survival;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {2985190R}, Number = {5}, Organization = {Department of Medical Biochemistry and Biophysics/Center of Excellence in Developmental Biology,Karolinska Institutet, Stockholm, Sweden.}, Pages = {1229-39}, Pii = {2243}, Pubmed = {15009679}, Title = {Region-specific generation of functional neurons from naive embryonic stem cells in adult brain}, Uuid = {D2E0FE39-13B5-4E08-BA99-A78701AF481C}, Volume = {88}, Year = {2004}, url = {papers/Harkany_JNeurochem2004.pdf}} @article{Harris:1991, Abstract = {Based on morphological, virological, biochemical and molecular biological data, it is proposed that the presence of endogenous retrovirus particles in the placental cytotrophoblasts of many mammals is indicative of some beneficial action provided by the virus in relation to cell fusion, syncytiotrophoblast formation and the creation of the placenta. Further, it is hypothesised that the germ line retroviral infection of some primitive mammal-like species resulted in the evolution of the placental mammals.}, Author = {Harris, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0014-5793}, Journal = {FEBS Lett}, Keywords = {15 ERVs retroelements;Female;Mammals;Placenta;Pregnancy;Evolution;15 Retrovirus mechanism;Animals;24 Pubmed search results 2008;review}, Medline = {92111751}, Month = {12}, Nlm_Id = {0155157}, Number = {1-3}, Organization = {Institute of Cell and Tumour Biology, German Cancer Research Center, Heidelberg.}, Pages = {3-4}, Pii = {0014-5793(91)81370-N}, Pubmed = {1765162}, Title = {The evolution of placental mammals}, Uuid = {6FE3A5AB-D6A0-41B1-B1DC-FAD397248927}, Volume = {295}, Year = {1991}, url = {papers/Harris_FEBSLett1991.pdf}} @article{Harris:2005, Abstract = {Cortical neurons show irregular but structured spike trains. This has been interpreted as evidence for 'temporal coding', whereby stimuli are represented by precise spike-timing patterns. Here, we suggest an alternative interpretation based on the older concept of the cell assembly. The dynamic evolution of assembly sequences, which are steered but not deterministically controlled by sensory input, is the proposed substrate of psychological processes beyond simple stimulus-response associations. Accordingly, spike trains show a temporal structure that is stimulus-dependent and more variable than would be predicted by strict sensory control. We propose four signatures of assembly organization that can be experimentally tested. We argue that many observations that have been interpreted as evidence for temporal coding might instead reflect an underlying assembly structure.}, Author = {Harris, Kenneth D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {24 Pubmed search results 2008;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;Hippocampus;Nerve Net;Animals;Humans;Cerebral Cortex;review;Neurons}, Month = {5}, Nlm_Id = {100962781}, Number = {5}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, New Jersey 07102, USA. kdharris\@andromeda.rutgers.edu}, Pages = {399-407}, Pii = {nrn1669}, Pubmed = {15861182}, Title = {Neural signatures of cell assembly organization}, Uuid = {5900A326-8636-4A12-80AC-00DD5829E610}, Volume = {6}, Year = {2005}, url = {papers/Harris_NatRevNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1669}} @article{Harris:2002, Abstract = {According to the temporal coding hypothesis, neurons encode information by the exact timing of spikes. An example of temporal coding is the hippocampal phase precession phenomenon, in which the timing of pyramidal cell spikes relative to the theta rhythm shows a unidirectional forward precession during spatial behaviour. Here we show that phase precession occurs in both spatial and non-spatial behaviours. We found that spike phase correlated with instantaneous discharge rate, and processed unidirectionally at high rates, regardless of behaviour. The spatial phase precession phenomenon is therefore a manifestation of a more fundamental principle governing the timing of pyramidal cell discharge. We suggest that intrinsic properties of pyramidal cells have a key role in determining spike times, and that the interplay between the magnitude of dendritic excitation and rhythmic inhibition of the somatic region is responsible for the phase assignment of spikes. 0028-0836 Journal Article}, Author = {Harris, K. D. and Henze, D. A. and Hirase, H. and Leinekugel, X. and Dragoi, G. and Czurko, A. and Buzsaki, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Nature}, Keywords = {18 Classic Neuroanatomy Physiology;*Action Potentials;Sleep, REM/physiology;Kinetics;*Theta Rhythm;Rats;Dendrites/physiology;Analysis of Variance;Motor Activity/physiology;M;Computer Simulation;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;Male;Pyramidal Cells/*physiology}, Number = {6890}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, New Jersey 07102, USA.}, Pages = {738-41}, Pubmed = {12066184}, Title = {Spike train dynamics predicts theta-related phase precession in hippocampal pyramidal cells}, Uuid = {850DC798-699A-478D-9BB4-F3322906B7F9}, Volume = {417}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12066184}} @article{Harris:2001, Abstract = {Cortical pyramidal cells fire single spikes and complex spike bursts. However, neither the conditions necessary for triggering complex spikes, nor their computational function are well understood. CA1 pyramidal cell burst activity was examined in behaving rats. The fraction of bursts was not reliably higher in place field centers, but rather in places where discharge frequency was 6-7 Hz. Burst probability was lower and bursts were shorter after recent spiking activity than after prolonged periods of silence (100 ms-1 s). Burst initiation probability and burst length were correlated with extracellular spike amplitude and with intracellular action potential rising slope. We suggest that bursts may function as "conditional synchrony detectors,"signaling strong afferent synchrony after neuronal silence, and that single spikes triggered by a weak input may suppress bursts evoked by a subsequent strong input. 0896-6273 Journal Article}, Author = {Harris, K. D. and Hirase, H. and Leinekugel, X. and Henze, D. A. and Buzsaki, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuron}, Keywords = {18 Classic Neuroanatomy Physiology;Hippocampus/*cytology;Behavior, Animal/physiology;Rats, Long-Evans;Rats;Time Factors;M;Support, U.S. Gov't, P.H.S.;Electrophysiology;Support, Non-U.S. Gov't;Animals;Male;Pyramidal Cells/*physiology;Action Potentials/*physiology}, Number = {1}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, NJ 07102, USA.}, Pages = {141-9}, Pubmed = {11604145}, Title = {Temporal interaction between single spikes and complex spike bursts in hippocampal pyramidal cells}, Uuid = {0DDF8381-0144-4E70-8F86-282CDDD62B7B}, Volume = {32}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11604145}} @article{Harris:2004, Abstract = {Analysis of developmental plasticity of bone marrow-derived cells (BMDCs) is complicated by the possibility of cell-cell fusion. Here we demonstrate that epithelial cells can develop from BMDCs without cell-cell fusion. We use the Cre/lox system together with beta-galactosidase and enhanced green fluorescent protein expression in transgenic mice to identify epithelial cells in the lung, liver, and skin that develop from BMDCs without cell fusion.}, Author = {Harris, Robert G. and Herzog, Erica L. and Bruscia, Emanuela M. and Grove, Joanna E. and Van Arnam, John S. and Krause, Diane S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Cell Differentiation;22 Stem cells;Elapid Venoms;Recombinases;Epithelial Cells;Green Fluorescent Proteins;24 Pubmed search results 2008;Radiation, Ionizing;Luminescent Proteins;Male;Animals;Direct Lytic Factors;Research Support, U.S. Gov't, P.H.S.;X Chromosome;Y Chromosome;Keratin;Bone Marrow Transplantation;08 Aberrant cell cycle;Hepatocytes;beta-Galactosidase;Muscle Cells;Female;Bone Marrow Cells;Stem Cells;Recombination, Genetic;Mice;Cell Fusion;Research Support, Non-U.S. Gov't;Mice, Transgenic;Reverse Transcriptase Polymerase Chain Reaction;Keratinocytes}, Month = {7}, Nlm_Id = {0404511}, Number = {5680}, Organization = {Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.}, Pages = {90-3}, Pii = {305/5680/90}, Pubmed = {15232107}, Title = {Lack of a fusion requirement for development of bone marrow-derived epithelia}, Uuid = {5CC0E045-CDD5-4813-B0E8-1F60CA48FCD5}, Volume = {305}, Year = {2004}, url = {papers/Harris_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1098925}} @article{Harrison:2007, Abstract = {Sex is determined in Drosophila by the activity of the Sex-lethal master regulator. Activity of Sex-lethal is initiated early in females by chromosome-counting transcription factors, then reinforced by signaling through the Janus kinase pathway.}, Author = {Harrison, Douglas A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Janus Kinases;Sex Determination (Genetics);Female;Alternative Splicing;Drosophila Proteins;Gene Expression Regulation;Signal Transduction;Drosophila;comment;Animals;24 Pubmed search results 2008;review;Transcription Factors}, Month = {5}, Nlm_Id = {9107782}, Number = {9}, Organization = {Biology Department, University of Kentucky, Lexington, Kentucky 40506, USA. DougH\@email.uky.edu}, Pages = {R328-30}, Pii = {S0960-9822(07)01113-X}, Pubmed = {17470347}, Title = {Sex determination: controlling the master}, Uuid = {A4DA062B-BB79-4093-895A-5FC6CB711E07}, Volume = {17}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2007.03.012}} @article{Harrison:2003, Abstract = {The expression of a number of chemokines and chemokine receptors by cells resident in normal and pathological central nervous system (CNS) tissue has been characterized by in situ hybridization techniques. As a result, our understanding of the role of this cytokine family in neurobiology has been enhanced greatly. Specific methods for detecting chemokine and chemokine receptor mRNAs in situ vary with the number of these genes that have been characterized and encompass approaches widely utilized by other investigators characterizing cell-specific gene expression patterns. We describe methods that our laboratory has used successfully in characterizing chemokine and chemokine receptor expression in the CNS, focusing on protocols that utilize radiolabeled in vitro-transcribed riboprobes for detecting these transcripts. Because general dye-based histological staining methods do not readily differentiate astrocytes and microglia, specific immunohistochemical protocols are required for definitive localization of gene expression to these glial cell types. As such, methods that are compatible with the in situ hybridization procedure are included for staining astrocytes and microglia.}, Author = {Harrison, Jeffrey K. and Luo, Defang and Streit, Wolfgang J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {1046-2023}, Journal = {Methods}, Keywords = {In Situ Hybridization;Dyes;Neuroglia;Central Nervous System;Immunohistochemistry;Rats;Astrocytes;Not relevant;Plasmids;Chemokines;Transcription, Genetic;11 Glia;Blotting, Northern;Animals;RNA, Messenger;Receptors, Chemokine;Oxazines}, Medline = {22613545}, Month = {4}, Nlm_Id = {9426302}, Number = {4}, Organization = {Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610-0267, USA. harrison\@pharmacology.ufl.edu}, Pages = {312-8}, Pii = {S1046202302003547}, Pubmed = {12725797}, Title = {In situ hybridization analysis of chemokines and chemokine receptors in the central nervous system}, Uuid = {0F1225E4-DB47-4E80-9054-399F9D1F725E}, Volume = {29}, Year = {2003}} @article{Harrison:1998, Abstract = {A recently identified chemokine, fractalkine, is a member of the chemokine gene family, which consists principally of secreted, proinflammatory molecules. Fractalkine is distinguished structurally by the presence of a CX3C motif as well as transmembrane spanning and mucin-like domains and shows atypical constitutive expression in a number of nonhematopoietic tissues, including brain. We undertook an extensive characterization of this chemokine and its receptor CX3CR1 in the brain to gain insights into use of chemokine-dependent systems in the central nervous system. Expression of fractalkine in rat brain was found to be widespread and localized principally to neurons. Recombinant rat CX3CR1, as expressed in Chinese hamster ovary cells, specifically bound fractalkine and signaled in the presence of either membrane-anchored or soluble forms of fractalkine protein. Fractalkine stimulated chemotaxis and elevated intracellular calcium levels of microglia; these responses were blocked by anti-CX3CR1 antibodies. After facial motor nerve axotomy, dramatic changes in the levels of CX3CR1 and fractalkine in the facial nucleus were evident. These included increases in the number and perineuronal location of CX3CR1-expressing microglia, decreased levels of motor neuron-expressed fractalkine mRNA, and an alteration in the forms of fractalkine protein expressed. These data describe mechanisms of cellular communication between neurons and microglia, involving fractalkine and CX3CR1, which occur in both normal and pathological states of the central nervous system.}, Author = {Harrison, J. K. and Jiang, Y. and Chen, S. and Xia, Y. and Maciejewski, D. and McNamara, R. K. and Streit, W. J. and Salafranca, M. N. and Adhikari, S. and Thompson, D. A. and Botti, P. and Bacon, K. B. and Feng, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Hamsters;Animals;Cloning, Molecular;Rats;Brain;Microglia;CHO Cells;Rats, Sprague-Dawley;Recombinant Fusion Proteins;11 Glia;Male;Chemokines, CX3C;Chemokines, CXC;Support, U.S. Gov't, P.H.S.;Motor Neurons;Amino Acid Sequence;Molecular Sequence Data;Membrane Proteins}, Medline = {98393742}, Month = {9}, Nlm_Id = {7505876}, Number = {18}, Organization = {Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA.}, Pages = {10896-901}, Pubmed = {9724801}, Title = {Role for neuronally derived fractalkine in mediating interactions between neurons and CX3CR1-expressing microglia}, Uuid = {1F5F030A-69AC-49DD-8ABF-F2D13794A159}, Volume = {95}, Year = {1998}, url = {papers/Harrison_ProcNatlAcadSciUSA1998.pdf}} @article{Hart:2006, Abstract = {The X-linked gene filamin A (Flna) encodes a widely expressed actin-binding protein that crosslinks actin into orthogonal networks and interacts with a variety of other proteins including membrane proteins, integrins, transmembrane receptor complexes and second messengers, thus forming an important intracellular signalling scaffold. Heterozygous loss of function of human FLNA causes periventricular nodular heterotopia in females and is generally lethal (cause unknown) in hemizygous males. Missense FLNA mutations underlie a spectrum of disorders affecting both sexes that feature skeletal dysplasia accompanied by a variety of other abnormalities. Dilp2 is an X-linked male-lethal mouse mutation that was induced by N-ethyl-N-nitrosourea. We report here that Dilp2 is caused by a T-to-A transversion that converts a tyrosine codon to a stop codon in the Flna gene (Y2388X), leading to absence of the Flna protein and male lethality because of incomplete septation of the outflow tract of the heart, which produces common arterial trunk. A proportion of both male and female mutant mice have other cardiac defects including ventricular septal defect. In addition, mutant males have midline fusion defects manifesting as sternum and palate abnormalities. Carrier females exhibit milder sternum and palate defects and misshapen pupils. These results define crucial roles for Flna in development, demonstrate that X-linked male lethal mutations can be recovered from ENU mutagenesis screens and suggest possible explanations for lethality of human males hemizygous for null alleles of FLNA.}, Author = {Hart, Alan W. and Morgan, Joanne E. and Schneider, J{\"u}rgen and West, Katrine and McKie, Lisa and Bhattacharya, Shoumo and Jackson, Ian J. and Cross, Sally H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:47 -0400}, Issn = {0964-6906}, Journal = {Hum Mol Genet}, Keywords = {Mice, Inbred BALB C;10 Development;Heterozygote;Embryo Loss;Genes, Lethal;Animals;Pupil Disorders;Mice, Mutant Strains;Microfilament Proteins;Pregnancy;Phenotype;Osteogenesis;Genes, X-Linked;Female;Heart Defects, Congenital;research support, non-u.s. gov't;Point Mutation;Male;Bone and Bones;10 genetics malformation;Sex Characteristics;Loss of Heterozygosity;Mice;24 Pubmed search results 2008;Contractile Proteins;Palate;Gene Expression;Mutant Proteins}, Month = {8}, Nlm_Id = {9208958}, Number = {16}, Organization = {Comparative and Developmental Genetics Section, MRC Human Genetics Unit, Edinburgh EH4 2XU, UK.}, Pages = {2457-67}, Pii = {ddl168}, Pubmed = {16825286}, Title = {Cardiac malformations and midline skeletal defects in mice lacking filamin A}, Uuid = {54AE64C9-D05A-43D4-948F-5E7259B58154}, Volume = {15}, Year = {2006}, url = {papers/Hart_HumMolGenet2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/hmg/ddl168}} @article{Hartenstein:1981, Abstract = {After several large cortical injections of horseradish peroxidase, individual callosal axons could be observed in most cortical areas contralateral to the injected hemisphere. They left the white matter and travelled for various distances (up to 2 mm) deep in layer VI, then turned to penetrate the cortex radially or obliquely, giving collaterals to several layers and forming narrow terminal arborisations in supragranular layers. In addition, callosal fibers were seen predominantly in deep cortical layers, which fibers could be interpreted either as collaterals of the thick fibers or as a distinct class of callosal afferents.}, Author = {Hartenstein, V. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Axons;Axonal Transport;Not relevant;11 Glia;Afferent Pathways;Horseradish Peroxidase;Animals;Cerebral Cortex;Mice;Corpus Callosum}, Medline = {81198107}, Month = {4}, Nlm_Id = {7600130}, Number = {1}, Pages = {19-24}, Pubmed = {6164965}, Title = {The arborization of single callosal axons in the mouse cerebral cortex}, Uuid = {D59203E1-1681-461F-B31E-C28F62829228}, Volume = {23}, Year = {1981}} @article{Hartfuss:2003, Abstract = {Radial glial cells are characterized, besides their astroglial properties, by long radial processes extending from the ventricular zone to the pial surface, a crucial feature for the radial migration of neurons. The molecular signals that regulate this characteristic morphology, however, are largely unknown. We show an important role of the secreted molecule reelin for the establishment of radial glia processes. We describe a significant reduction in ventricular zone cells with long radial processes in the absence of reelin in the cortex of reeler mutant mice. These defects were correlated to a decrease in the content of brain lipid-binding protein (Blbp) and were detected exclusively in the cerebral cortex, but not in the basal ganglia of reeler mice. Conversely, reelin addition in vitro increased the Blbp content and process extension of radial glia from the cortex, but not the basal ganglia. Isolation of radial glia by fluorescent-activated cell sorting showed that these effects are due to direct signaling of reelin to radial glial cells. We could further demonstrate that this signaling requires Dab1, as the increase in Blbp upon reelin addition failed to occur in Dab1-/- mice. Taken together, these results unravel a novel role of reelin signaling to radial glial cells that is crucial for the regulation of their Blbp content and characteristic morphology in a region-specific manner.}, Author = {Hartfuss, Eva and F{\"o}rster, Eckart and Bock, Hans H. and Hack, Michael A. and Leprince, Pierre and Luque, Juan M. and Herz, Joachim and Frotscher, Michael and G{\"o}tz, Magdalena}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {10 Development;Cell Differentiation;Signal Transduction;Animals;10 Hippocampus;Carrier Proteins;Cell Surface Extensions;Cell Adhesion Molecules, Neuronal;Mice, Inbred C57BL;Recombinant Fusion Proteins;Serine Endopeptidases;Mice, Neurologic Mutants;Extracellular Matrix Proteins;Research Support, U.S. Gov't, P.H.S.;Cell Size;Neurons;Neuroglia;Cerebral Cortex;Mice;Fatty Acid-Binding Proteins;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {22806427}, Month = {10}, Nlm_Id = {8701744}, Number = {19}, Organization = {Max-Planck-Institute of Neurobiology, Neuronal Specification, Am Klopferspitz 18a, D-82152 Martinsried, Germany.}, Pages = {4597-609}, Pii = {130/19/4597}, Pubmed = {12925587}, Title = {Reelin signaling directly affects radial glia morphology and biochemical maturation}, Uuid = {EEEA839C-8C1B-43ED-9391-BFD703C66BD5}, Volume = {130}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.00654}} @article{Hartman:2006, Abstract = {Neural activity regulates the number and properties of GABAergic synapses in the brain, but the mechanisms underlying these changes are unclear. We found that blocking spike activity globally in developing hippocampal neurons from rats reduced the density of GABAergic terminals as well as the frequency and amplitude of miniature inhibitory postsynaptic currents (mIPSCs). Chronic inactivity later in development led to a reduction in the mIPSC amplitude, without any change in GABAergic synapse density. By contrast, hyperpolarizing or abolishing spike activity in single neurons did not alter GABAergic synaptic inputs. Suppressing activity in individual presynaptic GABAergic neurons also failed to decrease synaptic output. Our results indicate that GABAergic synapses are regulated by the level of activity in surrounding neurons. Notably, we found that the expression of GABAergic plasticity involves changes in the amount of neurotransmitter in individual vesicles.}, Author = {Hartman, Kenichi N. and Pal, Sumon K. and Burrone, Juan and Murthy, Venkatesh N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Microtubule-Associated Proteins;research support, n.i.h., extramural ;Electric Stimulation;Vesicular Glutamate Transport Protein 1;Animals;Carrier Proteins;Rats;Transfection;Cells, Cultured;Synaptic Transmission;research support, u.s. gov't, non-p.h.s. ;Patch-Clamp Techniques;comparative study ;Hippocampus;Tetrodotoxin;research support, non-u.s. gov't ;Pyridines;Animals, Newborn;Glutamate Decarboxylase;21 Neurophysiology;Neurons;Phosphinic Acids;Membrane Potentials;Potassium Channels, Inwardly Rectifying;24 Pubmed search results 2008;Drug Interactions;Isoenzymes;Membrane Proteins;Neural Inhibition}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.}, Pages = {642-9}, Pii = {nn1677}, Pubmed = {16582905}, Title = {Activity-dependent regulation of inhibitory synaptic transmission in hippocampal neurons}, Uuid = {96CAEA94-0F25-4C6C-9E68-DD63534A5167}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1677}} @article{Harwell:2005, Abstract = {Regulation of gene transcription by neuronal activity is thought to be key to the translation of sensory experience into long-term changes in synaptic structure and function. Here we show that cpg15, a gene encoding an extracellular signaling molecule that promotes dendritic and axonal growth and synaptic maturation, is regulated in the somatosensory cortex by sensory experience capable of inducing cortical plasticity. Using in situ hybridization, we monitored cpg15 expression in 4-week-old mouse barrel cortex after trimming all whiskers except D1. We found that cpg15 expression is depressed in the deprived barrels and enhanced in the barrel column corresponding to the spared D1 whisker. Changes in cpg15 mRNA levels first appear in layer IV, peak 12 h after deprivation, and then decline rapidly. In layers II/III, changes in cpg15 expression appear later, peak at 24 h, and persist for days. Induction of cpg15 expression is significantly diminished in adolescent as well as adult CREB knockout mice. cpg15's spatio-temporal expression pattern and its regulation by CREB are consistent with a role in experience-dependent plasticity of cortical circuits. Our results suggest that local structural and/or synaptic changes may be a mechanism by which the adult cortex can adapt to peripheral manipulations.}, Author = {Harwell, Corey and Burbach, Barry and Svoboda, Karel and Nedivi, Elly}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {research support, n.i.h., extramural ;Animals;Gene Expression Regulation;research support, u.s. gov't, p.h.s. ;comparative study ;Vibrissae;Mice, Inbred C57BL;Physical Stimulation;Time Factors;research support, non-u.s. gov't ;In Situ Hybridization;Cyclic AMP Response Element-Binding Protein;Mice, Knockout;21 Neurophysiology;Somatosensory Cortex;Mice;24 Pubmed search results 2008;Membrane Proteins;Nerve Tissue Proteins}, Month = {10}, Nlm_Id = {0213640}, Number = {1}, Organization = {The Picower Center for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 50 Ames Street, E18-670, Cambridge, Massachusetts 02139, USA.}, Pages = {85-96}, Pubmed = {16010668}, Title = {Regulation of cpg15 expression during single whisker experience in the barrel cortex of adult mice}, Uuid = {AE104EA4-321D-4A07-9304-E39746FB1959}, Volume = {65}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.20176}} @article{Hasan:2004, Abstract = {Genetically encoded fluorescent calcium indicator proteins (FCIPs) are promising tools to study calcium dynamics in many activity-dependent molecular and cellular processes. Great hopes-for the measurement of population activity, in particular-have therefore been placed on calcium indicators derived from the green fluorescent protein and their expression in (selected) neuronal populations. Calcium transients can rise within milliseconds, making them suitable as reporters of fast neuronal activity. We here report the production of stable transgenic mouse lines with two different functional calcium indicators, inverse pericam and camgaroo-2, under the control of the tetracycline-inducible promoter. Using a variety of in vitro and in vivo assays, we find that stimuli known to increase intracellular calcium concentration (somatically triggered action potentials (APs) and synaptic and sensory stimulation) can cause substantial and rapid changes in FCIP fluorescence of inverse pericam and camgaroo-2.}, Author = {Hasan, Mazahir T. and Friedrich, Rainer W. and Euler, Thomas and Larkum, Matthew E. and Giese, G{\"u}nter and Both, Matthias and Duebel, Jens and Waters, Jack and Bujard, Hermann and Griesbeck, Oliver and Tsien, Roger Y. and Nagai, Takeharu and Miyawaki, Atsushi and Denk, Winfried}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {Retina;Signal Transduction;Animals;Photic Stimulation;Humans;Transfection;research support, u.s. gov't, p.h.s. ;Brain;Mice, Transgenic;23 Technique;comparative study ;Calcium;Microscopy, Fluorescence;Hela Cells;21 Calcium imaging;Fluorescence Recovery After Photobleaching;research support, non-u.s. gov't ;Olfactory Bulb;21 Neurophysiology;Calcium Channels;Mice;Doxycycline;24 Pubmed search results 2008;Luminescent Proteins;Gene Expression;Brain Mapping}, Month = {6}, Nlm_Id = {101183755}, Number = {6}, Organization = {Max Planck Institute for Medical Research, Heidelberg, Germany. mhasan\@mpimf-heidelberg.mpg.de}, Pages = {e163}, Pubmed = {15208716}, Title = {Functional fluorescent Ca2+ indicator proteins in transgenic mice under TET control}, Uuid = {0935A4F6-7B6F-49C2-97A9-879C973B2258}, Volume = {2}, Year = {2004}, url = {papers/Hasan_PLoSBiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0020163}} @article{Hase:2002, Abstract = {The present study aimed to analyse how anatomical regeneration contributes to functional recovery after experimental spinal cord repair. Thoracic spinal cord of neonatal rats was completely transected to make a gap and repaired by grafting a section of embryonic spinal cord. Six weeks after surgery, outcome of locomotor performance was assessed using an open field locomotor scale (BBB scale). Axonal regeneration across the repaired site was quantitatively assessed in the raphe, vestibular, and red nuclei and the sensorimotor cortex by a retrograde tracing method. The rats that had no labelled neurons in any of the supraspinal nuclei showed no hind-forelimb coordination. The rats that had labelled neurons in the brainstem nuclei but not in the sensorimotor cortex showed hind-forelimb coordination of varying grades depending on the amount of regeneration. The rats that had labelled neurons in all of the examined nuclei showed almost normal locomotion. In addition to a relationship between distribution of the labelled neurons and functional recovery, a positive correlation was observed between number of the labelled neurons in each of the supraspinal nuclei and locomotor performance of the rat. Thus the grade of restored function appeared to be regulated by distribution and number of fibres regenerated across the repaired site and into the target region. These results suggest that accurate reconstruction of neural connections is essential for significant functional recovery after spinal cord repair.}, Author = {Hase, Takao and Kawaguchi, Saburo and Hayashi, Hideki and Nishio, Takeshi and Mizoguchi, Akira and Nakamura, Takashi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Fetus;Pregnancy;Animals;Efferent Pathways;Brain Tissue Transplantation;Rats;Recovery of Function;Brain;Female;Axons;Rats, Wistar;Spinal Cord;Nerve Regeneration;Spinal Cord Injuries;Animals, Newborn;24 Pubmed search results 2008;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {21916982}, Month = {3}, Nlm_Id = {8918110}, Number = {6}, Organization = {Department of Integrative Brain Science, Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan.}, Pages = {969-74}, Pii = {1932}, Pubmed = {11918656}, Title = {Spinal cord repair in neonatal rats: a correlation between axonal regeneration and functional recovery}, Uuid = {4B23BFD2-24FC-43A5-A731-0AF2204ED832}, Volume = {15}, Year = {2002}} @article{Hashizume:2004, Abstract = {The results of clinical and experimental studies on epilepsy associated with focal cortical dysplasia (FCD) are presented. We have been interested in the findings of abnormal increases in the numbers of small vessels in specimens of FCD resected from epilepsy patients. In the clinical study of 13 patients with epilepsy, specimens of FCD or dysembryoplastic neuroepithelial tumor (DNT) were examined using immunohistochemistry. The number of vessels in both lesions were greater than those in cortical specimens of autopsy cases without epilepsy. Because the vessels showed negative staining of VEGF, it was thought that the phenomenon of increase in the number of vessels was simply a hypervascularity, not a neovascularity. The local hypervascularity was expected to show local hyperperfusion in CBF-SPECT study, but interictal SPECT demonstrated local hypoperfusion and ictal SPECT showed hyperperfusion. This may have been caused by a functional change in those vessels. In the experimental study, we tried to make a new animal model of FCD to study epileptogenicity of FCD. When kainic acid had been infused into the neocortex in the neonatal rats, FCD was induced in adult Wistar rats. Histopathological examination revealed cortical dyslamination and abnormal neurons. On EEG, local spike bursts were elicited from the lesions, however, clinical seizures were not detected. Although the data are preliminary and observation over a longer period is required to determine whether spontaneous seizures will occur in this model, it is expected that this new model will be useful for studying epilepsy associated with FCD.}, Author = {Hashizume, Kiyotaka and Tsuda, Hiroshige and Hodozuka, Akira and Tanaka, Tatsuya}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1323-1316}, Journal = {Psychiatry Clin Neurosci}, Keywords = {Animals;Neoplasms, Neuroepithelial;Rats;Brain;21 Epilepsy;Excitatory Amino Acid Agonists;Epilepsy;Rats, Wistar;Cerebrovascular Circulation;Motor Cortex;Male;Kainic Acid;Brain Neoplasms;Disease Models, Animal;Animals, Newborn;21 Neurophysiology;Somatosensory Cortex;24 Pubmed search results 2008;Immunohistochemistry;Electroencephalography;Blood Vessels}, Month = {6}, Nlm_Id = {9513551}, Number = {3}, Organization = {Department of Neurosurgery, Asahikawa Medical College, Asahikawa, Japan. kmark113\@asahikawa-med.ac.jp}, Pages = {S26-9}, Pii = {PCN1244_7}, Pubmed = {15149312}, Title = {Clinical and experimental studies of epilepsy associated with focal cortical dysplasia}, Uuid = {0F343945-FDAC-4CC7-A141-8597E91BD0A8}, Volume = {58}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1440-1819.2004.01244_7.x}} @article{Hastings:1999, Abstract = {The dentate gyrus continues to produce granule neurons throughout adulthood. The present study examined the extension of axons by adult- generated granule neurons into hippocampal area CA3. We injected the fluorescent retrograde tracers Fast blue (FB) and FluoroRuby (FR) into area CA3 of adult male rats at various times after the administration of 5'-bromo-2'-deoxyuridine (BrdU), a marker of proliferating cells and their progeny. We report that immature granule cells extend axons into CA3 as rapidly as 4-10 days after mitosis. A significant increase in the percentage of BrdU-labeled cells that were labeled with FB or FR was observed by 2 weeks after BrdU administration. This proportion remained roughly constant up to 3 weeks after BrdU-labeling, a time at which markers of a mature neuronal phenotype are expressed. BrdU- labeled cells that contained either FB or FR often were located far from the tracer injection site, indicating that these cells had extended relatively long axons. Collectively these results suggest that adult-generated granule neurons may influence normal hippocampal function, even at a very early stage after their production.}, Author = {Hastings, N. B. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Fluorescent Dyes;Neural Pathways/physiology/ultrastructure;Animals;Axons/*physiology;Aging;Rats;Neural Pathways;Hippocampus/*physiology/ultrastructure;Animal;Cell Count;02 Adult neurogenesis migration;Dentate Gyrus/physiology/ultrastructure;Rats, Sprague-Dawley;Axons;Hippocampus;Time Factors;Male;Aging/pathology/*physiology;Research Support, U.S. Gov't, P.H.S.;B;Neurons;Dentate Gyrus;Support, U.S. Gov't, P.H.S.;24 Pubmed search results 2008;Bromodeoxyuridine;Immunohistochemistry;Neurons/*physiology/ultrastructure}, Medline = {99395198}, Month = {10}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA. hastings\@princeton.edu}, Pages = {146-54.}, Pii = {10.1002/(SICI)1096-9861(19991011)413:1<146::AID-CNE10>3.0.CO;2-B}, Pubmed = {10464376}, Title = {Rapid extension of axons into the CA3 region by adult-generated granule cells}, Uuid = {3992BB66-9C25-475A-9D68-33D10ABF2B9E}, Volume = {413}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10464376}} @article{Hastings:2002, Abstract = {Most excitatory intrahippocampal pathways are characterized by significant, highly ordered projections into the long, or septotemporal, hippocampal axis. However, the mossy fiber system, the excitatory projection by which the dentate gyrus projects to hippocampal area CA3, is considered an exception, being organized to innervate exclusively transversely oriented cortical layers of the hippocampus. In the present study, the anatomy of the rat mossy fiber system was investigated using axonal tracing techniques, with an emphasis on determining its projection pattern into the long hippocampal axis. To this end, we used dual ipsilateral retrograde tracer injections to determine whether individual granule cells extend divergent axon collaterals to septotemporally distinct levels of hippocampal area CA3. We combined this technique with the fluorescent immunohistochemical detection of 5-bromo-2'-deoxyuridine (BrdU), a marker of granule cell precursors and their progeny, to address whether the divergence of mossy fiber collaterals within area CA3 might by related to ontogenic gradients in granule cell genesis. We observed single granule neurons that had retrogradely transported both tracers, indicating that they had axon collaterals passing through or terminating within the distinct levels of area CA3 into which tracer had been injected. By using BrdU labeling, we identified divergent granule neurons that were produced during embryonic and postnatal development. We observed no adult-generated granule neurons with significantly diverging mossy fiber collaterals. However, many fewer cells were labeled with BrdU in adult-exposed animals. Because of this smaller sample, we cannot rule out the possibility that small numbers of divergent adult-generated granule cells exist. We conclude that a proportion of the hippocampal mossy fiber projection extends septotemporally divergent axon collaterals to hippocampal area CA3.}, Author = {Hastings, Nicholas B. and Seth, Malika I. and Tanapat, Patima and Rydel, Tracy A. and Gould, Elizabeth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Pregnancy;Animals;Rats;Neural Pathways;Female;Axons;Rats, Sprague-Dawley;Hippocampus;Male;Antimetabolites;Mossy Fibers, Hippocampal;Research Support, U.S. Gov't, P.H.S.;Neurons;Dentate Gyrus;Cell Division;24 Pubmed search results 2008;Bromodeoxyuridine;Immunohistochemistry;Biological Markers}, Medline = {22242085}, Month = {10}, Nlm_Id = {0406041}, Number = {4}, Organization = {Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA. hastings\@princeton.edu}, Pages = {324-33}, Pubmed = {12355416}, Title = {Granule neurons generated during development extend divergent axon collaterals to hippocampal area CA3}, Uuid = {31E5AFA1-5E0F-41F0-8020-B763F99F8C83}, Volume = {452}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10386}} @article{Hata:1999, Abstract = {Activity-dependent competition is thought to guide the normal development of specific patterns of neural connections. Such competition generally favors more active inputs, making them larger and stronger, while less active inputs become smaller and weaker. We pharmacologically inhibited the activity of visual cortical cells and measured the three-dimensional structure of inputs serving the two eyes when one eye was occluded. The more active inputs serving the open eye actually became smaller than the deprived inputs from the occluded eye, which were similar to those in normal animals. These findings demonstrate in vivo that it is not the amount of afferent activity but the correlation between cortical and afferent activity that regulates the growth or retraction of these inputs.}, Author = {Hata, Y. and Tsumoto, T. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Visual Cortex;Sensory Deprivation;research support, non-u.s. gov't;Dendrites;21 Neurophysiology;Cats;Geniculate Bodies;Neuronal Plasticity;Neural Inhibition;21 Activity-development;Muscimol;research support, u.s. gov't, p.h.s.;Animals;Neurons, Afferent;GABA Agonists;Vision, Monocular;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Neurophysiology, Biomedical Research Center, Osaka University Medical School, Suita, Japan. hata\@nphys.med.osaka-u.ac.jp}, Pages = {375-81}, Pii = {S0896-6273(00)81097-1}, Pubmed = {10069342}, Title = {Selective pruning of more active afferents when cat visual cortex is pharmacologically inhibited}, Uuid = {26D2F01B-38D9-4AF9-815B-BCC7A522320D}, Volume = {22}, Year = {1999}, url = {papers/Hata_Neuron1999.pdf}} @article{Hatanaka:2002, Abstract = {During development neurons migrate from their site of origin to their final destinations under a variety of mechanisms. Although evidence has been accumulating that the cells from cortical ventricular zone (VZ) migrate radially and produce pyramidal cells, evidence that directly links the origin and the terminal phenotype of radially migrating cells has been limited. Further, the relation between the migratory behavior of these cells and their mature morphology remains obscure. To address these issues, we developed an in vitro preparation that enables visualization of cells derived from the cortical VZ. VZ cells of a rat cortex at embryonic days 18 to 19 were labeled by injecting green fluorescent protein (GFP)-encoding plasmid into the lateral ventricle, followed by electroporation. The cortex was then sliced and cultured organotypically. After 1 day, GFP(+) cells exhibited neural progenitor and radial glial cell natures. Over the next few days, many GFP(+) cells migrated toward the pial surface, extending leading processes toward the pial surface and leaving a thin trailing process that almost reached the VZ. The leading processes of these neurons were positive for microtubule-associated protein 2, and some transformed into dendritic arbor-like structures by day 5 or 6, and their trailing processes exhibited morphologic features indicative of prospective axons. Time-lapse analysis confirmed extension of the trailing processes. Expression of molecular markers and morphologic analysis demonstrated that the vast majority of the migrated GFP(+) cells differentiated into excitatory neurons with pyramidal cell-like morphology. These results strongly suggested that cells derived from the cortical VZ generate neurons that migrate radially. These neurons appeared to extend prospective dendrites in front and leave prospective axons behind, subsequently differentiating into pyramidal cells.}, Author = {Hatanaka, Yumiko and Murakami, Fujio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Fluorescent Dyes;Microtubule-Associated Proteins;Cell Differentiation;Animals;In Vitro;Rats;Cell Movement;Axons;Pyramidal Cells;Rats, Wistar;11 Glia;Green Fluorescent Proteins;Injections, Intraventricular;Dendrites;Mice, Inbred ICR;Cerebral Ventricles;Plasmids;Cell Lineage;Cerebral Cortex;Neuroglia;Mice;Luminescent Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {22297222}, Month = {12}, Nlm_Id = {0406041}, Number = {1}, Organization = {Division of Behavior and Neurobiology, National Institute for Basic Biology, Okazaki, Aichi 444-8585, Japan. yumiko\@nibb.ac.jp}, Pages = {1-14}, Pubmed = {12410614}, Title = {In vitro analysis of the origin, migratory behavior, and maturation of cortical pyramidal cells}, Uuid = {C3362B1A-A354-470B-98C6-BABD96FC287B}, Volume = {454}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10421}} @article{Hatch:1994, Abstract = {Some children infected by HIV-1 demonstrate nervous system disease. Because a significant percentage of these children are believed to be infected during gestation and it is thought that HIV-1 may infect distinct glial populations, this work tested the hypothesis that different HIV-1 isolates can infect cells of the developing human fetal central nervous system (CNS). Central nervous system organotypic tissue cultures derived from human fetal brain enable the study of complex interactions between CNS cell types. Central nervous system organotypic cultures were exposed to lymphocytotropic (L-tropic) or monocytotropic (M-tropic) HIV-1 isolates and monitored for viral infection. HIV-1 gp41 and p24 antigens were detected by immunocytochemistry (ICC), HIV-1 RNA was localized in the cytoplasm of CNS cells by in situ hybridization (ISH), and viral DNA was detected by polymerase chain reaction (PCR) in HIV-1-exposed cultures. Double-label ICC identified HIV-1 antigens in both microglia and astrocytes. These results demonstrate that both L- and M-tropic isolates infect microglia and astrocytes in human fetal organotypic cultures. In addition, HIV-1 infection was detected in culture supernatants up to day 57 postinfection and at 90 days by coculture with susceptible CEM cells. HIV-1 infection of neural cells appears to be productive. This model may permit further examination of the interaction of HIV-1 with the developing human CNS and the mechanisms of AIDS-associated neuropathology.}, Author = {Hatch, W. C. and Pousada, E. and Losev, L. and Rashbaum, W. K. and Lyman, W. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0889-2229}, Journal = {AIDS Res Hum Retroviruses}, Keywords = {Fetus;Human;Tissue Culture;HIV-1;Astrocytes;Base Sequence;Humans;Microglia;Female;Culture Techniques;11 Glia;Giant Cells;DNA Primers;Research Support, U.S. Gov't, P.H.S.;Neurons;Support, U.S. Gov't, P.H.S.;Virus Replication;Molecular Sequence Data;Central Nervous System}, Medline = {95194725}, Month = {12}, Nlm_Id = {8709376}, Number = {12}, Organization = {Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461.}, Pages = {1597-607}, Pubmed = {7888218}, Title = {Neural cell targets of human immunodeficiency virus type 1 in human fetal organotypic cultures}, Uuid = {BCFCEB98-EA03-4BAB-A599-A10CFE15A3A0}, Volume = {10}, Year = {1994}} @article{Hatfield:2005, Abstract = {One of the key characteristics of stem cells is their capacity to divide for long periods of time in an environment where most of the cells are quiescent. Therefore, a critical question in stem cell biology is how stem cells escape cell division stop signals. Here, we report the necessity of the microRNA (miRNA) pathway for proper control of germline stem cell (GSC) division in Drosophila melanogaster. Analysis of GSCs mutant for dicer-1 (dcr-1), the double-stranded RNaseIII essential for miRNA biogenesis, revealed a marked reduction in the rate of germline cyst production. These dcr-1 mutant GSCs exhibit normal identity but are defective in cell cycle control. On the basis of cell cycle markers and genetic interactions, we conclude that dcr-1 mutant GSCs are delayed in the G1 to S transition, which is dependent on the cyclin-dependent kinase inhibitor Dacapo, suggesting that miRNAs are required for stem cells to bypass the normal G1/S checkpoint. Hence, the miRNA pathway might be part of a mechanism that makes stem cells insensitive to environmental signals that normally stop the cell cycle at the G1/S transition.}, Author = {Hatfield, S. D. and Shcherbata, H. R. and Fischer, K. A. and Nakahara, K. and Carthew, R. W. and Ruohola-Baker, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-13 09:45:17 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Research Support, Non-U.S. Gov't;G1 Phase;S Phase;Gene Deletion;Research Support, U.S. Gov't, P.H.S.;Drosophila Proteins;Cell Division;Drosophila melanogaster;Genome;Nuclear Proteins;Research Support, N.I.H., Extramural;MicroRNAs;Stem Cells;Animals;Ribonuclease III;24 Pubmed search results 2008; microRNAs; development}, Month = {6}, Nlm_Id = {0410462}, Number = {7044}, Organization = {Department of Biochemistry, University of Washington, J591, HSB, Seattle, Washington 98195-7350, USA.}, Pages = {974-8}, Pii = {nature03816}, Pubmed = {15944714}, Title = {Stem cell division is regulated by the microRNA pathway}, Uuid = {E9BF0371-4995-441E-9A68-31ABFFBFFAB4}, Volume = {435}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03816}} @article{Hatten:1999, Abstract = {Widespread cell migrations are the hallmark of vertebrate brain development. In the early embryo, morphogenetic movements of precursor cells establish the rhombomeres of the hindbrain, the external germinal layer of the cerebellum, and the regional boundaries of the forebrain. In midgestation, after primary neurogenesis in compact ventricular zones has commenced, individual postmitotic cells undergo directed migrations along the glial fiber system. Radial migrations establish the neuronal layers. Three molecules have been shown to function in glial guided migration--astrotactin, glial growth factor, and erbB. In the postnatal period, a wave of secondary neurogenesis produces huge numbers of interneurons destined for the cerebellar cortex, the hippocampal formation, and the olfactory bulb. Molecular analysis of the genes that mark stages of secondary neurogenesis show similar expression patterns of a number of genes. Thus these three regions may have genetic pathways in common. Finally, we consider emerging studies on neurological mutant mice, such as reeler, and human brain malformations. Positional cloning and identification of mutated genes has led to new insights on laminar patterning in brain. 0147-006x Journal Article Review Review, Tutorial}, Author = {Hatten, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {Annu Rev Neurosci}, Keywords = {Cell Movement/physiology;Cerebellar Cortex/embryology/physiology;Neurons/*physiology;Human;Embryo and Fetal Development/physiology;Mice, Neurologic Mutants/physiology;Central Nervous System/*cytology/embryology;Animals;F pdf;Mice;Embryo/anatomy &histology/physiology;Cerebral Cortex/cytology/embryology}, Organization = {Rockefeller University, New York, New York 10021-6399, USA. hatten\@rockvax.rockefeller.edu}, Pages = {511-39}, Pubmed = {10202547}, Title = {Central nervous system neuronal migration}, Uuid = {AD8AEEDC-A3E5-11DA-AB00-000D9346EC2A}, Volume = {22}, Year = {1999}, url = {papers/Hatten_AnnuRevNeurosci1999.pdf}} @article{Hatten:2002, Abstract = {Over the past decade, genetic analyses have yielded a more molecular view of neuronal migration and its role in central nervous system development. We now realize that many of the molecular mechanisms that guide migrations in invertebrates are recapitulated in the vertebrate nervous system. These mechanisms guide dorsoventral and anterior-posterior migrations and merge with radial migratory pathways that are prominent in the development of the mammalian cortex. This review discusses the choreography of these different migratory mechanisms within the context of genetic approaches that have defined their molecular mechanisms. 1095-9203 Journal Article Review Review, Tutorial}, Author = {Hatten, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:48 -0400}, Journal = {Science}, Keywords = {10 Development;F both;*Caenorhabditis elegans Proteins;Telencephalon/cytology;Nerve Growth Factors/physiology;Neurons/*cytology;Cell Movement/*physiology;Animals;Vertebrates;*Nerve Tissue Proteins;Helminth Proteins/physiology;Neuroglia/physiology}, Number = {5587}, Organization = {Laboratory of Developmental Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10021-6399, USA. hatten\@rockefeller.edu}, Pages = {1660-3}, Title = {New directions in neuronal migration}, Uuid = {4071EC2D-FF38-4275-AC6E-D1F5CD50A1F4}, Volume = {297}, Year = {2002}, url = {papers/Hatten_Science2002.pdf}} @article{Hattori:2007, Abstract = {Neurons are thought to use diverse families of cell-surface molecules for cell recognition during circuit assembly. In Drosophila, alternative splicing of the Down syndrome cell adhesion molecule (Dscam) gene potentially generates 38,016 closely related transmembrane proteins of the immunoglobulin superfamily, each comprising one of 19,008 alternative ectodomains linked to one of two alternative transmembrane segments. These ectodomains show isoform-specific homophilic binding, leading to speculation that Dscam proteins mediate cell recognition. Genetic studies have established that Dscam is required for neural circuit assembly, but the extent to which isoform diversity contributes to this process is not known. Here we provide conclusive evidence that Dscam diversity is essential for circuit assembly. Using homologous recombination, we reduced the entire repertoire of Dscam ectodomains to just a single isoform. Neural circuits in these mutants are severely disorganized. Furthermore, we show that it is crucial for neighbouring neurons to express distinct isoforms, but that the specific identity of the isoforms expressed in an individual neuron is unimportant. We conclude that Dscam diversity provides each neuron with a unique identity by which it can distinguish its own processes from those of other neurons, and that this self-recognition is essential for wiring the Drosophila brain.}, Author = {Hattori, Daisuke and Demir, Ebru and Kim, Ho Won and Viragh, Erika and Zipursky, S. Lawrence and Dickson, Barry J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Mutation;10 Development;research support, non-u.s. gov't;Mushroom Bodies;Alleles;Alternative Splicing;Drosophila Proteins;10 circuit formation;Drosophila melanogaster;Protein Isoforms;research support, n.i.h., extramural;Animals;Brain;24 Pubmed search results 2008;Neurons}, Month = {9}, Nlm_Id = {0410462}, Number = {7159}, Organization = {Department of Biological Chemistry, Howard Hughes Medical Institute, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90049, USA.}, Pages = {223-7}, Pii = {nature06099}, Pubmed = {17851526}, Title = {Dscam diversity is essential for neuronal wiring and self-recognition}, Uuid = {8F5D54EB-70C7-4F5C-97E2-A763990A6D0E}, Volume = {449}, Year = {2007}, url = {papers/Hattori_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06099}} @article{Haubensak:2004, Abstract = {Neurons of the mammalian CNS are thought to originate from progenitors dividing at the apical surface of the neuroepithelium. Here we use mouse embryos expressing GFP from the Tis21 locus, a gene expressed throughout the neural tube in most, if not all, neuron-generating progenitors, to specifically reveal the cell divisions that produce CNS neurons. In addition to the apical, asymmetric divisions of neuroepithelial (NE) cells that generate another NE cell and a neuron, we find, from the onset of neurogenesis, a second population of progenitors that divide in the basal region of the neuroepithelium and generate two neurons. Basal progenitors are most frequent in the telencephalon, where they outnumber the apically dividing neuron-generating NE cells. Our observations reconcile previous data on the origin and lineage of CNS neurons and show that basal, rather than apical, progenitors are the major source of the neurons of the mammalian neocortex.}, Author = {Haubensak, Wulf and Attardo, Alessio and Denk, Winfried and Huttner, Wieland B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {10 Development;Heterozygote;Cell Cycle Proteins;Animals;Microscopy, Video;Aging;Epithelial Cells;Rhombencephalon;Mitosis;Female;Telencephalon;Mice, Transgenic;Mice, Inbred C57BL;Recombinant Fusion Proteins;Green Fluorescent Proteins;Embryonic and Fetal Development;Crosses, Genetic;Male;Genes, Tumor Suppressor;Neurons;Immediate-Early Proteins;Mice;Luminescent Proteins;Genes, Reporter;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {7505876}, Notes = {there is suppl pdf info in omega data as well}, Number = {9}, Organization = {Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.}, Pages = {3196-201}, Pii = {0308600100}, Pubmed = {14963232}, Title = {Neurons arise in the basal neuroepithelium of the early mammalian telencephalon: a major site of neurogenesis}, Uuid = {53316EC6-8CBE-4D47-9A33-90C3446F85B4}, Volume = {101}, Year = {2004}, url = {papers/Haubensak_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0308600100}} @article{Haun:1993, Abstract = {Unilateral lesions extending across the boundary region of visual and parietal cortex in adult rats result in the death of 20-35\%of neurons in layers II-III of the caudal third of medial frontal cortex ipsilaterally, a neuron population labeled with 3H-thymidine on the 19th day of gestation (E19). Additionally, there is a consistent 15\%loss of these labeled neurons in an area between 50\%and 60\%of the distance along the caudal-rostral extent of medial frontal cortex, an area that may function analogously to the frontal eye field of primates. All of these neurons are rescued from axotomy-induced death by delivering into the posterior cortex lesion cavity for 2 weeks a macromolecular fraction of culture medium conditioned by embryonic primordia of the frontal-occipital pathway (CM). Moreover, the rescue is apparently permanent, with normal numbers of these neurons present in CM animals 6-7 weeks after the neurotrophic factor is no longer being supplied exogenously. Behaviorally, control operates receiving a similarly prepared fraction of unconditioned medium are significantly impaired in the number of trials needed to learn two visual discrimination tasks. This deficit is attributable in part to a bias in erroneous responses to the side contralateral to the lesion. The error bias reflects a failure to inhibit repeated incorrect responding contralaterally. In contrast, the CM animals learn both visual tasks in a normal number of trials and have no contralateral error bias. Rather, all CM animals have an contralateral error bias. Rather, all CM animals have an ipsilateral error bias (interpreted as an unmasking of the contralateral neglect expected after a parietal cortex lesion).(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Haun, F. and Cunningham, T. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Visual Cortex;Frontal Lobe;Neurons;Pattern Recognition, Visual;Discrimination Learning;Rats;Research Support, U.S. Gov't, P.H.S.;Cell Survival;Occipital Lobe;Vision;Parietal Lobe;Culture Techniques;Culture Media;Animals;24 Pubmed search results 2008;Nerve Growth Factors;Axons}, Medline = {93147933}, Month = {2}, Nlm_Id = {8102140}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19129.}, Pages = {614-22}, Pubmed = {8426229}, Title = {Recovery of frontal cortex-mediated visual behaviors following neurotrophic rescue of axotomized neurons in medial frontal cortex}, Uuid = {6CEF1EF3-976B-4AB4-9943-AED60B470839}, Volume = {13}, Year = {1993}} @article{Hayakawa:2003, Abstract = {Studies have indicated that bone marrow contains both hematopoietic stem cells and mesenchymal stem cells that can differentiate into a variety of mesenchymal tissues, such as bone, cartilage, muscle, and adipose tissue. Therefore, bone marrow cells are thought to be very useful for cell and gene therapy for various diseases. However, the multipotentiality of these cells remains unclear. To address this issue, we established a chimeric model mouse stably reconstituted with green fluorescent protein (GFP)-marked bone marrow cells. We injected bone marrow cells from GFP-transgenic C57BL/6 mice into the tail veins of recipient wild-type C57BL/6 mice that had been irradiated with a lethal dose of 10 Gy from a cesium source. Microscopic examination and fluorescence-assisted cell sorter (FACS) analysis showed that bone marrow cells, including mesenchymal cells, were almost completely reconstituted with GFP+ cells 5 weeks after transplantation. FACS analysis with lineage-specific antibodies confirmed that the GFP+ cells could differentiate into all types of blood cells. To confirm the usefulness of this mouse model, we studied the role of circulating bone marrow-derived cells in healing of damaged intestine. We performed amputation and anastomosis of the jejunum 10 cm from the pyloric region of the stomach. On the third day after operation, a large number of GFP+ cells were infiltrated in the area of anastomosis, and these cells were positive for CD45 and F4/80 antigens. In 7 days, several cells became negative for CD45 and F4/80 and positive for alpha smooth muscle actin antigen, which is specific for smooth muscle. This finding suggested that bone marrow-derived cells had differentiated into smooth muscle. Because reconstituted bone marrow cells as opposed to injected bone marrow cells, behave naturally, this model is ideal for studying the multipotentiality of bone marrow cells in vivo.}, Author = {Hayakawa, Jun and Migita, Makoto and Ueda, Takahiro and Shimada, Takashi and Fukunaga, Yoshitaka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0925-5710}, Journal = {Int J Hematol}, Keywords = {Myocytes, Smooth Muscle;Flow Cytometry;Cell Differentiation;Luminescent Proteins;Models, Animal;Bone Marrow Cells;Regeneration;Mice, Inbred C57BL;Bone Marrow Transplantation;11 Glia;Mice, Transgenic;Green Fluorescent Proteins;Jejunum;Mice;Cell Movement;Animals;Transplantation Chimera}, Medline = {22724912}, Month = {6}, Nlm_Id = {9111627}, Number = {5}, Organization = {Department of Pediatrics, Center for Advanced Medical Technology, Nippon Medical School, Tokyo, Japan.}, Pages = {456-62}, Pubmed = {12841383}, Title = {Generation of a chimeric mouse reconstituted with green fluorescent protein-positive bone marrow cells: a useful model for studying the behavior of bone marrow cells in regeneration in vivo}, Uuid = {AE8FD54A-504A-4FB2-B025-B47A7360BBC7}, Volume = {77}, Year = {2003}} @article{Hayakawa:2005, Abstract = {Recent studies have shown multiple differences between humans and apes in sialic acid (Sia) biology, including Siglecs (Sia-recognizing-Ig-superfamily lectins). Comparisons with the chimpanzee genome indicate that human SIGLEC11 emerged through human-specific gene conversion by an adjacent pseudogene. Conversion involved 5 cent untranslated sequences and the Sia-recognition domain. This human protein shows reduced binding relative to the ancestral form but recognizes oligosialic acids, which are enriched in the brain. SIGLEC11 is expressed in human but not in chimpanzee brain microglia. Further studies will determine if this event was related to the evolution of Homo.}, Author = {Hayakawa, Toshiyuki and Angata, Takashi and Lewis, Amanda L. and Mikkelsen, Tarjei S. and Varki, Nissi M. and Varki, Ajit}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Animals;Humans;Brain;Exons;Pan troglodytes;Phylogeny;Microglia;Pseudogenes;11 Glia;Gene Conversion;Pongo pygmaeus;Evolution;Research Support, U.S. Gov't, P.H.S.;Sialic Acids;19 Neocortical evolution;Regulatory Sequences, Nucleic Acid;Membrane Proteins;Research Support, N.I.H., Extramural;Lectins;Research Support, Non-U.S. Gov't}, Month = {9}, Nlm_Id = {0404511}, Number = {5741}, Organization = {Glycobiology Research and Training Center, University of California at San Diego, La Jolla, CA 92093, USA.}, Pages = {1693}, Pii = {309/5741/1693}, Pubmed = {16151003}, Title = {A human-specific gene in microglia}, Uuid = {869DE839-F0EB-4AA3-80E6-FFF8094C90A1}, Volume = {309}, Year = {2005}, url = {papers/Hayakawa_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1114321}} @article{Haydar:2000, Abstract = {Recent studies have implicated the classical neurotransmitters GABA and glutamate in the regulation of neural progenitor proliferation. We now show that GABA and glutamate have opposite effects on the two neural progenitor populations in the ventricular zones (VZs) and subventricular zones (SVZs) of the embryonic cerebrum. Application of either molecule to organotypic slice cultures dramatically increases proliferation in the VZ by shortening the cell cycle, whereas proliferation in the SVZ is decreased. These disparate effects, measured both by bromodeoxyuridine uptake and the expansion of retrovirally labeled progenitor clones, are mimicked by the application of specific GABA and glutamate agonists and are blocked by antagonists. Thus, the relative contributions of the VZ and SVZ to neocortical growth may be regulated by differential responsiveness to GABA and glutamate. 0270-6474 Journal Article}, Author = {Haydar, T. F. and Wang, F. and Schwartz, M. L. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurosci}, Keywords = {10 Development;Animals;Bromodeoxyuridine/pharmacology;Kainic Acid/pharmacology;Neurons/*cytology;F abstr;Excitatory Amino Acid Antagonists/pharmacology;Cerebral Ventricles/chemistry/*cytology/embryology;Muscimol/pharmacology;Stem Cells/*cytology/drug effects;Cell Division/drug effects/physiology;Clone Cells/drug effects/physiology;Neocortex/chemistry/*cytology/embryology;Glutamic Acid/analysis/*pharmacology;Mice, Inbred ICR;Excitatory Amino Acid Agonists/pharmacology;Cell Movement/drug effects/physiology;Antimetabolites/pharmacology;GABA Agonists/pharmacology;Cell Differentiation/drug effects/physiology;Support, U.S. Gov't, P.H.S.;Mice;GABA Antagonists/pharmacology;6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology;Organ Culture;gamma-Aminobutyric Acid/analysis/*pharmacology;Fetus/cytology}, Number = {15}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.}, Pages = {5764-74}, Pubmed = {10908617}, Title = {Differential modulation of proliferation in the neocortical ventricular and subventricular zones}, Uuid = {BB2FAF94-87DD-4C4A-87D8-9E6FF4E91144}, Volume = {20}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10908617}} @article{Haydar:2005, Abstract = {Studies on human patients and animal models of disease have shown that disruptions in prenatal and early postnatal brain development are a root cause of mental retardation. Since proper brain development is achieved by a strict spatiotemporal control of neurogenesis, cell migration, and patterning of synapses, abnormalities in one or more of these events during prenatal development can lead to cognitive dysfunction after birth. Many of underlying causes of mental retardation must therefore be studied in developing brains. To aid in this research, live imaging using laser scanning microscopy (LSM) has recently allowed neuroscientists to delve deeply into the complex three-dimensional environment of the living brain to record dynamic cellular events over time. This review will highlight recent examples of how LSM is being applied to elucidate both normal and abnormal cortical development.}, Author = {Haydar, Tarik F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1080-4013}, Journal = {Ment Retard Dev Disabil Res Rev}, Keywords = {Pregnancy;Cell Differentiation;Down Syndrome;Absorptiometry, Photon;Humans;Microscopy, Confocal;Brain;Apoptosis;Female;Cell Movement;21 Epilepsy;review;Mental Retardation;Neurons;21 Neurophysiology;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Fragile X Syndrome}, Nlm_Id = {9517974}, Number = {4}, Organization = {Center for Neuroscience Research, Children's Research Institute, Children's National Medical Center, Washington, DC 20010, USA. thaydar\@cnmcresearch.org}, Pages = {303-16}, Pubmed = {16240412}, Title = {Advanced microscopic imaging methods to investigate cortical development and the etiology of mental retardation}, Uuid = {51D05EF6-F039-47F7-A44E-DDC3EF0F7015}, Volume = {11}, Year = {2005}, url = {papers/Haydar_MentRetardDevDisabilResRev2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/mrdd.20088}} @article{Haydar:2003, Abstract = {The mode of neural stem cell division in the forebrain proliferative zones profoundly influences neocortical growth by regulating the number and diversity of neurons and glia. Long-term time-lapse multiphoton microscopy of embryonic mouse cortex reveals new details of the complex three-dimensional rotation and oscillation of the mitotic spindle before stem cell division. Importantly, the duration and amplitude of spindle movement predicts and specifies the eventual mode of mitotic division. These technological advances have provided dramatic data and insights into the kinetics of neural stem cell division by elucidating the involvement of spindle rotation in selection of the cleavage plane and the mode of neural stem cell division that together determine the size of the mammalian neocortex. 22506285 0027-8424 Journal Article}, Author = {Haydar, T. F. and Ang, E. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Nervous System/cytology;Telencephalon/*embryology/*metabolism;10 Development;Image Processing, Computer-Assisted;Time Factors;Cell Division;Animal;Mice, Inbred ICR;Brain/pathology;Support, U.S. Gov't, P.H.S.;F;Neurons/*cytology;Support, Non-U.S. Gov't;Mice;Photons;Mitotic Spindle Apparatus/chemistry/*physiology}, Number = {5}, Organization = {Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA.}, Pages = {2890-5}, Pubmed = {12589023}, Title = {Mitotic spindle rotation and mode of cell division in the developing telencephalon}, Uuid = {0D76DEAD-EAF6-4831-AC44-171244E56F35}, Volume = {100}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12589023}} @article{Haydon:2001, Abstract = {Glial cells are emerging from the background to become more prominent in our thinking about integration in the nervous system. Given that glial cells associated with synapses integrate neuronal inputs and can release transmitters that modulate synaptic activity, it is time to rethink our understanding of the wiring diagram of the nervous system. It is no longer appropriate to consider solely neuron-neuron connections; we also need to develop a view of the intricate web of active connections among glial cells, and between glia and neurons. Without such a view, it might be impossible to decode the language of the brain. 1471-003x Journal Article Review Review, Tutorial}, Author = {Haydon, P. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {G;Glutamic Acid/metabolism;Gap Junctions/physiology;Synapses/*physiology;Synaptic Transmission/*physiology;Signal Transduction/physiology;Schwann Cells/metabolism;11 Glia;Support, U.S. Gov't, P.H.S.;Neuroglia/*physiology/ultrastructure;Animals;Astrocytes/physiology;Calcium Signaling;Neurons/*physiology/ultrastructure;Calcium/metabolism}, Number = {3}, Organization = {Department of Zoology and Genetics, Iowa State University, Ames, Iowa 50011, USA. pghaydon\@iastate.edu}, Pages = {185-93}, Pubmed = {11256079}, Title = {GLIA: listening and talking to the synapse}, Uuid = {AD1698E7-784B-4923-837F-4B6E502CBE89}, Volume = {2}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11256079}} @article{Hayes:2000, Abstract = {Two S-phase markers for in vivo studies of cell proliferation in the developing central nervous system, tritiated thymidine ((3)H-TdR) and bromodeoxyuridine (BUdR), were compared using double-labeling techniques in the developing mouse cortex at embryonic day 14 (E14). The labeling efficiencies and detectability of the two tracers were approximately equivalent, and there was no evidence of significant tracer interactions that depend on order of administration. For both tracers, the loading time needed to label an S-phase cell to detectability is estimated at <0.2 h shortly after the injection of the label, but, as the concentration of the label falls, it increases to approximately 0.65 h after about 30 min. Thereafter, cells that enter the S-phase continue to become detectably labeled for approximately 5-6 h. The approximate equivalence of these two tracers was exploited to observe directly the numbers and positions of nuclei entering (labeled with the second tracer only) and leaving (labeled with the first tracer only) the S-phase. As expected, the numbers of nuclei entering and leaving the S-phase both increased as the interval between the two injections lengthened. Also, nuclei leaving the S-phase rapidly move towards the ventricular surface during G2, but, unexpectedly, the distribution of the entering nuclei does not differ significantly from the distribution of the nuclei in the S-phase. This indicates that: (1) the extent and rate of abventricular nuclear movement during G1 is variable, such that not all nuclei traverse the entire width of the ventricular zone, and (2) interkinetic nuclear movements are minimal during S-phase.}, Author = {Hayes, N. L. and Nowakowski, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Embryo;Thymidine;Mice;24 Pubmed search results 2008;S Phase;Immunohistochemistry;Research Support, U.S. Gov't, P.H.S.;Research Support, U.S. Gov't, Non-P.H.S.;Animals;Bromodeoxyuridine;Cerebral Cortex;Cell Nucleus;Mice, Inbred Strains}, Medline = {20125899}, Nlm_Id = {7809375}, Number = {1-2}, Organization = {Department of Neuroscience, UMDNJ - Robert Wood Johnson Medical School, Piscataway, N.J., USA. hayes\@umdnj.edu}, Pages = {44-55}, Pii = {dne22044}, Pubmed = {10657697}, Title = {Exploiting the dynamics of S-phase tracers in developing brain: interkinetic nuclear migration for cells entering versus leaving the S-phase}, Uuid = {4B306C29-E44B-4BE1-A9DA-D2D1386DA412}, Volume = {22}, Year = {2000}} @article{Haynes:2006, Abstract = {Microglia are primary immune sentinels of the CNS. Following injury, these cells migrate or extend processes toward sites of tissue damage. CNS injury is accompanied by release of nucleotides, serving as signals for microglial activation or chemotaxis. Microglia express several purinoceptors, including a G(i)-coupled subtype that has been implicated in ATP- and ADP-mediated migration in vitro. Here we show that microglia from mice lacking G(i)-coupled P2Y(12) receptors exhibit normal baseline motility but are unable to polarize, migrate or extend processes toward nucleotides in vitro or in vivo. Microglia in P2ry(12)(-/-) mice show significantly diminished directional branch extension toward sites of cortical damage in the living mouse. Moreover, P2Y(12) expression is robust in the 'resting' state, but dramatically reduced after microglial activation. These results imply that P2Y(12) is a primary site at which nucleotides act to induce microglial chemotaxis at early stages of the response to local CNS injury.}, Author = {Haynes, Sharon E. and Hollopeter, Gunther and Yang, Guang and Kurpius, Dana and Dailey, Michael E. and Gan, Wen-Biao B. and Julius, David}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9809671}, Number = {12}, Organization = {Departments of Physiology & Cellular and Molecular Pharmacology, University of California, San Francisco (UCSF), 600 16th Street, San Francisco, California 94158-2517, USA.}, Pages = {1512-9}, Pii = {nn1805}, Pubmed = {17115040}, Title = {The P2Y(12) receptor regulates microglial activation by extracellular nucleotides}, Uuid = {DA1AF3BF-16A3-4397-9B27-57EC6B0DDDCD}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1805}} @article{Hazan:2006, Abstract = {Recent technological advances now allow for simultaneous recording of large populations of anatomically distributed neurons in behaving animals. The free software package described here was designed to help neurophysiologists process and view recorded data in an efficient and user-friendly manner. This package consists of several well-integrated applications, including NeuroScope (http://neuroscope.sourceforce.net), an advanced viewer for electrophysiological and behavioral data with limited editing capabilities, Klusters (http://klusters.sourceforge.net), a graphical cluster cutting application for manual and semi-automatic spike sorting, NDManager (GPL,see http://www.gnu.org/licenses/gpl.html), an experimental parameter and data processing manager. All of these programs are distributed under the GNU General Public License (GPL, see ), which gives its users legal permission to copy, distribute and/or modify the software. Also included are extensive user manuals and sample data, as well as source code and documentation.}, Author = {Hazan, Lynn and Zugaro, Micha{\"e}l and Buzs{\'a}ki, Gy{\"o}rgy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {research support, non-u.s. gov't;Programming Languages;Neurophysiology;Computer Graphics;Cluster Analysis;comparative study;research support, n.i.h., extramural;User-Computer Interface;Animals;Humans;Automatic Data Processing;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {7905558}, Number = {2}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, NJ 07102, USA.}, Pages = {207-16}, Pii = {S0165-0270(06)00041-0}, Pubmed = {16580733}, Title = {Klusters, NeuroScope, NDManager: a free software suite for neurophysiological data processing and visualization}, Uuid = {731DF2C7-CFA1-4F86-9FC3-DD95E24B5AC6}, Volume = {155}, Year = {2006}, url = {papers/Hazan_JNeurosciMethods2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2006.01.017}} @article{He:2008, Abstract = {Using a transgenic mouse line in which GFP is expressed in a single population of retinal ganglion cells (RGCs), Huberman and colleagues report in this issue of Neuron that the axon terminals of RGCs exhibit an orderly pattern of distribution in the higher visual centers. This pattern undergoes a developmental refinement, and synchronous activity in the retina regulates columnar but not laminar formation.}, Author = {He, Shigang}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {Retina;Retinal Ganglion Cells;comment;Animals;Visual Pathways;24 Pubmed search results 2008;Mice;Axons}, Month = {8}, Nlm_Id = {8809320}, Number = {3}, Organization = {State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 15 Da-tun Road, Beijing 100101, China. shiganghe\@moon.ibp.ac.cn}, Pages = {352-3}, Pii = {S0896-6273(08)00635-1}, Pubmed = {18701060}, Title = {Alpha cells take off first}, Uuid = {8B40B752-69D3-48A7-BCA8-1388590770AA}, Volume = {59}, Year = {2008}, url = {papers/He_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.08.001}} @article{Heck:2006, Abstract = {The cortical migration process depends on a number of trophic factors and on the activation of different voltage- and ligand-gated channels. We investigated the role of gamma-aminobutyric acid (GABA) type A receptors in the neuronal migration process of the newborn rat parietal cortex in vivo and in vitro. Local in vivo application of the GABA-A antagonist bicuculline methiodide (BMI) or the agonist muscimol via cortical surface Elvax implants induced prominent alterations in the cortical architecture when compared with untreated or sham-operated controls. BMI- and muscimol-treated animals revealed heterotopic cell clusters in the upper layers and a complete loss of the cortical lamination in the region underlying the Elvax implant. Immunocytochemical staining for glial fibrillary acidic protein, N-methyl-D-aspartate receptors, and GABA demonstrated that heterotopia was not provoked by glial proliferation and confirmed the presence of both glutamatergic and GABAergic neurons. In organotypic neocortical slices from embryonic day 18-19 embryos, application of BMI and to a lesser extent also muscimol induced an increase in the migration speed and an accumulation of neurons in the upper cortical layers. Spontaneous intracellular calcium ([Ca(2+)]i) oscillations in neocortical slices from newborn rats were abolished by BMI (5 and 20 microM) and muscimol (1 and 10 microM), indicating that both compounds interfere with [Ca(2+)]i signaling required for normal neuronal migration. Electrophysiological recordings from migrating neurons in newborn rat neocortical slices indicate that long-term application of muscimol causes a pronounced reduction (1 microM muscimol) or blockade (10 microM) in the responsiveness of postsynaptic GABA-A receptors due to a pronounced receptor desensitization. Our results indicate that modulation of GABA-A receptors by compounds acting as agonists or antagonists may profoundly influence the neuronal migration process in the developing cerebral cortex.}, Author = {Heck, and Kilb, and Reiprich, and Kubota, and Furukawa, and Fukuda, and Luhmann,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {in vitro;Drug Implants;10 Development;Electrophysiology;Animals;GABA Agonists;Rats;Neocortex;Patch-Clamp Techniques;Cell Movement;Kinetics;Rats, Wistar;Calcium;research support, non-u.s. gov't;Antimetabolites;Bicuculline;Animals, Newborn;Receptors, GABA-A;Neurons;21 Neurophysiology;Muscimol;GABA Antagonists;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine;Receptors, N-Methyl-D-Aspartate;Glial Fibrillary Acidic Protein}, Month = {2}, Nlm_Id = {9110718}, Number = {1}, Organization = {Institute of Physiology and Pathophysiology, University of Mainz, Mainz, Germany.}, Pages = {138-48}, Pii = {bhj135}, Pubmed = {16452638}, Title = {GABA-A Receptors Regulate Neocortical Neuronal Migration In Vitro and In Vivo}, Uuid = {E859FE90-A0AB-4599-9AB3-E46D38090182}, Volume = {17}, Year = {2006}, url = {papers/Heck_CerebCortex2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhj135}} @article{Heck:2007, Abstract = {A massive neuronal loss during early postnatal development has been well documented in the murine cerebral cortex, but the factors that drive cells into apoptosis are largely unknown. The role of neuronal activity in developmental apoptosis was studied in organotypic neocortical slice cultures of newborn mice. Multielectrode array and whole-cell patch-clamp recordings revealed spontaneous network activity characterized by synchronized burst discharges, which could be blocked by tetrodotoxin and ionotropic glutamate receptor antagonists. The identical neuropharmacological manipulations also caused a significant increase in the number of apoptotic neurons as early as 6 h after the start of drug treatment. Moreover, inhibition of the NMDA receptor subunit NR2A or NR2B induced a differential short-term versus delayed increase in the apoptosis rate, respectively. Activation of L-type, voltage-dependent calcium channels was neuroprotective and could prevent activity-dependent apoptosis during NMDA receptor blockade. Furthermore, this effect involved phosphorylation of cAMP response element-binding protein and activation of the tropomyosin-related kinase (Trk) receptors. Inhibition of electrical synapses and blockade of ionotropic gamma-aminobutyric acid receptors induced specific changes in spontaneous electrical activity patterns, which caused an increase in caspase-3-dependent cell death. Our results demonstrate that synchronized spontaneous network bursts activating ionotropic glutamate receptors promote neuronal survival in the neonatal mouse cerebral cortex.}, Author = {Heck, and Golbs, and Riedemann, and Sun, and Lessmann, and Luhmann,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {21 Neurophysiology;21 Activity-development;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9110718}, Organization = {Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, D-55128 Mainz, Germany.}, Pii = {bhm165}, Pubmed = {17965127}, Title = {Activity-Dependent Regulation of Neuronal Apoptosis in Neonatal Mouse Cerebral Cortex}, Uuid = {EB33FE26-440E-4770-AF89-611D9E859833}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhm165}} @article{Hegg:1999, Abstract = {Microglia- and macrophage-induced neuronal death may underlie a number of neurodegenerative diseases. The effects of factors secreted by monocytic cells were studied on glutamatergic synaptic transmission between cultured rat hippocampal neurons. Conditioned media from differentiated human U937 cells was collected after 24 h and applied to neurons (0.5\%-30\%dilution). Unactivated U937 cells spontaneously released factors that when applied to neuronal cultures evoked bursts of action potentials and elicited neuronal death (29+/-4\%). Conditioned media collected from U937 cells evoked intracellular calcium ([Ca(2+)](i)) spiking (0.5\%-2\%dilution) and at higher concentrations evoked sustained increases in intracellular calcium (3\%-30\%dilution), as measured by indo-1-based photometry in single neurons. Activation of the U937 cells with zymosin A (500 microg/ml) enhanced the potency of the conditioned media to increase intraneuronal [Ca(2+)](i) as indicated by a leftward shift in the concentration-response curve. Selective antagonists to voltage-gated Na(+) and Ca(2+) channels and NMDA-gated channels (tetrodotoxin, nimodipine, and (+/-)-2-amino-5-phosphonopentanoic acid, respectively) blocked the calcium transients elicited by unactivated and zymosin -A-treated conditioned media. This pharmacologic profile is consistent with U937-released factors that excite the synaptic network that forms between cultured hippocampal neurons.}, Author = {Hegg, C. C. and Thayer, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0014-2999}, Journal = {Eur J Pharmacol}, Keywords = {U937 Cells;Neurotoxins;Excitatory Amino Acid Antagonists;Zymosan;6-Cyano-7-nitroquinoxaline-2,3-dione;Animals;Cells, Cultured;Hippocampus;Synapses;Receptors, N-Methyl-D-Aspartate;Nimodipine;Membrane Potentials;11 Glia;Culture Media, Conditioned;Support, U.S. Gov't, P.H.S.;Action Potentials;Support, U.S. Gov't, Non-P.H.S.;Tetrodotoxin;Pipecolic Acids;Rats;Glutamic Acid;Dose-Response Relationship, Drug;Fetus;Patch-Clamp Techniques;Monocytes;Calcium;Cell Death;Excitatory Amino Acids;Neurons;Human;Calcium Channel Blockers}, Medline = {20076374}, Month = {12}, Nlm_Id = {1254354}, Number = {2-3}, Organization = {Department of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St. SE, Minneapolis, MN 55455-0217, USA.}, Pages = {231-7}, Pii = {S0014299999007128}, Pubmed = {10607881}, Title = {Monocytic cells secrete factors that evoke excitatory synaptic activity in rat hippocampal cultures}, Uuid = {6BFA1FC8-1EB3-4A80-A8DE-663B7C383E9A}, Volume = {385}, Year = {1999}} @article{Hegstrom:1996, Abstract = {During metamorphosis in the moth, Manduca sexta, the abdominal body-wall muscle DEO1 is remodeled to form the adult muscle DE5. As the larval muscle degenerates, its motoneuron loses its end plates and retracts axon branches from the degenerating muscle. Muscle degeneration is under the control of the insect hormones, the ecdysteroids. Topical application of an ecdysteroid mimic resulted in animals that produced a localized patch of pupal cuticle. Muscle fibers underlying the patch showed a gradient of degeneration. The motoneuron showed end-plate loss and axon retraction from degenerating regions of a given fiber but maintained its fine terminal branches and end plates on intact regions. The results suggest that local steroid treatments that result in local muscle degeneration bring about a loss of synaptic contacts from regions of muscle degeneration.}, Author = {Hegstrom, C. D. and Truman, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Muscles;Animals;Synapses;Pupa;Microscopy, Confocal;Larva;Manduca;Female;Motor Endplate;Hydrazines;Cell Adhesion Molecules, Neuronal;Insect Hormones;Steroids;Axons;Synaptotagmins;Male;Ecdysteroids;Research Support, U.S. Gov't, P.H.S.;Antibody Specificity;Membrane Glycoproteins;Cyclic GMP;Calcium-Binding Proteins;Juvenile Hormones;Metamorphosis, Biological;Motor Neurons;24 Pubmed search results 2008;Immunohistochemistry;Nerve Tissue Proteins}, Medline = {97039647}, Month = {10}, Nlm_Id = {0213640}, Number = {2}, Organization = {Department of Zoology, University of Washington, Seattle 98195-1800, USA. hegstrom\@zoology.washington.edu}, Pages = {175-88}, Pii = {10.1002/(SICI)1097-4695(199610)31:2<175::AID-NEU4>3.0.CO;2-8}, Pubmed = {8885199}, Title = {Synapse loss and axon retraction in response to local muscle degeneration}, Uuid = {FD940BB3-5E01-4098-8BD8-6A65F8E51A95}, Volume = {31}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/(SICI)1097-4695(199610)31:2<175::AID-NEU4>3.0.CO;2-8}} @article{Heim:2007, Abstract = {Fluorescent Ca(2+) indicator proteins (FCIPs) are attractive tools for studying Ca(2+) dynamics in live cells. Here we describe transgenic mouse lines expressing a troponin C (TnC)-based biosensor. The biosensor is widely expressed in neurons and has improved Ca(2+) sensitivity both in vitro and in vivo. This allows FCIP-based two-photon Ca(2+) imaging of distinct neurons and their dendrites in vivo, and opens a new avenue for structure-function analysis of intact neuronal circuits.}, Author = {Heim, Nicola and Garaschuk, Olga and Friedrich, Michael W. and Mank, Marco and Milos, Ruxandra I. and Kovalchuk, Yury and Konnerth, Arthur and Griesbeck, Oliver}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {Calcium Signaling;Animals;Spectrometry, Fluorescence;Brain;Female;Mice, Transgenic;23 Technique;Mice, Inbred C57BL;Calcium;research support, non-u.s. gov't;Troponin C;Green Fluorescent Proteins;Dendrites;Male;Mice, Inbred Strains;Biosensing Techniques;Neurons;Mice;optical physiology;optical imaging;calcium imaging;frontiers review}, Month = {2}, Nlm_Id = {101215604}, Number = {2}, Organization = {Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried, Germany.}, Pages = {127-9}, Pii = {nmeth1009}, Pubmed = {17259991}, Title = {Improved calcium imaging in transgenic mice expressing a troponin C-based biosensor}, Uuid = {FE9D0565-55D5-4CE8-8439-5477E2293DA1}, Volume = {4}, Year = {2007}, url = {papers/Heim_NatMethods2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth1009}} @article{Heinrich:2006, Abstract = {Mesio-temporal lobe epilepsy (MTLE) is often accompanied by granule cell dispersion (GCD), a widening of the granule cell layer. The molecular determinants of GCD are poorly understood. Here, we used an animal model to study whether GCD results from an increased dentate neurogenesis associated with an abnormal migration of the newly generated granule cells. Adult mice were given intrahippocampal injections of kainate (KA) known to induce focal epileptic seizures and GCD, comparable to the changes observed in human MTLE. Ipsilateral GCD progressively developed after KA injection and was paralleled by a gradual decrease in the expression of doublecortin, a marker of newly generated granule cells, in the dentate subgranular layer. Staining with Fluoro-Jade B revealed little cell degeneration in the subgranular layer on the KA-injected side. Labeling with bromodeoxyuridine showed an early, transient increase in mitotic activity in the dentate gyrus of the KA-injected hippocampus that gave rise to microglial cells and astrocytes but not to new neurons. Moreover, at later time points, there was a virtually complete cessation of mitotic activity in the injected hippocampus (where GCD continued to develop), but not on the contralateral side (where no GCD was observed). Finally, a significant decrease in reelin mRNA synthesis in the injected hippocampus paralleled the development of GCD, and neutralization of reelin by application of the CR-50 antibody induced GCD. These results show that GCD does not result from increased neurogenesis but reflects a displacement of mature granule cells, most likely caused by a local reelin deficiency.}, Author = {Heinrich, Christophe and Nitta, Naoki and Flubacher, Armin and M{\"u}ller, Martin and Fahrner, Alexander and Kirsch, Matthias and Freiman, Thomas and Suzuki, Fumio and Depaulis, Antoine and Frotscher, Michael and Haas, Carola A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {17}, Organization = {Experimental Epilepsy Group, University of Freiburg, D-79106 Freiburg, Germany.}, Pages = {4701-13}, Pii = {26/17/4701}, Pubmed = {16641251}, Title = {Reelin deficiency and displacement of mature neurons, but not neurogenesis, underlie the formation of granule cell dispersion in the epileptic hippocampus}, Uuid = {888A02A1-450F-4491-B7B0-234F4F557C71}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5516-05.2006}} @article{Heins:2002, Abstract = {Radial glial cells, ubiquitous throughout the developing CNS, guide radially migrating neurons and are the precursors of astrocytes. Recent evidence indicates that radial glial cells also generate neurons in the developing cerebral cortex. Here we investigated the role of the transcription factor Pax6 expressed in cortical radial glia. We showed that radial glial cells isolated from the cortex of Pax6 mutant mice have a reduced neurogenic potential, whereas the neurogenic potential of non-radial glial precursors is not affected. Consistent with defects in only one neurogenic lineage, the number of neurons in the Pax6 mutant cortex in vivo is reduced by half. Conversely, retrovirally mediated Pax6 expression instructs neurogenesis even in astrocytes from postnatal cortex in vitro. These results demonstrated an important role of Pax6 as intrinsic fate determinant of the neurogenic potential of glial cells. 21912404 1097-6256 Journal Article}, Author = {Heins, N. and Malatesta, P. and Cecconi, F. and Nakafuku, M. and Tucker, K. L. and Hack, M. A. and Chapouton, P. and Barde, Y. A. and Gotz, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {Nat Neurosci}, Keywords = {Neurons/*physiology;Human;Cell Separation;10 Development;Cells, Cultured;Rats;Cell Movement/*physiology;Neuroglia/*physiology;Homeodomain Proteins/genetics/*metabolism;Animal;Mice, Transgenic;Mice, Inbred C57BL;Cerebral Cortex/cytology/embryology/*growth &development/physiology;Support, Non-U.S. Gov't;Cell Lineage;Flow Cytometry;Transcription Factors/genetics/metabolism;Mice;Luminescent Proteins/metabolism;F;Indicators and Reagents/metabolism;Transgenes/genetics}, Number = {4}, Organization = {Max-Planck Institute of Neurobiology, Am Klopferspitz 18a, 82152, Planegg-Martinsreid, Munich, Germany.}, Pages = {308-15}, Pubmed = {11896398}, Title = {Glial cells generate neurons: the role of the transcription factor Pax6}, Uuid = {82E2CF78-925E-47EB-B076-1ECE762D9814}, Volume = {5}, Year = {2002}, url = {papers/Heins_NatNeurosci2002}} @article{Helenius:1980, Author = {Helenius, A. and Kartenbeck, J. and Simons, K. and Fries, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {24 Pubmed search results 2008;Cell Membrane;Semliki forest virus;Chloroquine;Adsorption;Virus Replication;Cell Line;Get paper from library;Receptors, Virus;Lysosomes;Endocytosis;Fluorescent Antibody Technique;Animals;Kidney;Hamsters;15 Retrovirus mechanism;Microvilli}, Medline = {80204437}, Month = {2}, Nlm_Id = {0375356}, Number = {2}, Pages = {404-20}, Pubmed = {6991511}, Title = {On the entry of Semliki forest virus into BHK-21 cells}, Uuid = {79972FAC-6CA0-4959-B698-AC2F0A6AAC92}, Volume = {84}, Year = {1980}} @article{Hellstrom:1999, Abstract = {Development of a vascular system involves the assembly of two principal cell types - endothelial cells and vascular smooth muscle cells/pericytes (vSMC/PC) - into many different types of blood vessels. Most, if not all, vessels begin as endothelial tubes that subsequently acquire a vSMC/PC coating. We have previously shown that PDGF-B is critically involved in the recruitment of pericytes to brain capillaries and to the kidney glomerular capillary tuft. Here, we used desmin and alpha-smooth muscle actin (ASMA) as markers to analyze vSMC/PC development in PDGF-B-/- and PDGFR-beta-/- embryos. Both mutants showed a site-specific reduction of desmin-positive pericytes and ASMA-positive vSMC. We found that endothelial expression of PDGF-B was restricted to immature capillary endothelial cells and to the endothelium of growing arteries. BrdU labeling showed that PDGFR-beta-positive vSMC/PC progenitors normally proliferate at sites of endothelial PDGF-B expression. In PDGF-B-/- embryos, limb arterial vSMC showed a reduced BrdU-labeling index. This suggests a role of PDGF-B in vSMC/PC cell proliferation during vascular growth. Two modes of vSMC recruitment to newly formed vessels have previously been suggested: (1) de novo formation of vSMC by induction of undifferentiated perivascular mesenchymal cells, and (2) co-migration of vSMC from a preexisting pool of vSMC. Our data support both modes of vSMC/PC development and lead to a model in which PDGFR-beta-positive vSMC/PC progenitors initially form around certain vessels by PDGF-B-independent induction. Subsequent angiogenic sprouting and vessel enlargement involves PDGF-B-dependent vSMC/PC progenitor co-migration and proliferation, and/or PDGF-B-independent new induction of vSMC/PC, depending on tissue context.}, Author = {Hellstr{\"o}m, M. and Kal{\'e}n, M. and Lindahl, P. and Abramsson, A. and Betsholtz, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Blood Vessels;Cell Division;Animals;Receptors, Platelet-Derived Growth Factor;Mice, Mutant Strains;Pericytes;Brain;Arteries;Cell Movement;11 Glia;Mice, Inbred Strains;Platelet-Derived Growth Factor;Mice;Muscle, Smooth, Vascular;Proto-Oncogene Proteins;Proto-Oncogene Proteins c-sis;Desmin;Receptor, Platelet-Derived Growth Factor beta;Actins;Research Support, Non-U.S. Gov't}, Medline = {99307070}, Month = {6}, Nlm_Id = {8701744}, Number = {14}, Organization = {Department of Medical Biochemistry, G{\"o}teborg University, Box 440, SE 405 30 G{\"o}teborg, Sweden. christer.betsholtz\@medkem.gu.se}, Pages = {3047-55}, Pubmed = {10375497}, Title = {Role of PDGF-B and PDGFR-beta in recruitment of vascular smooth muscle cells and pericytes during embryonic blood vessel formation in the mouse}, Uuid = {87E9B23C-1E32-4FC6-9FE5-69167DAAAF1C}, Volume = {126}, Year = {1999}} @article{Helmchen:2007, Abstract = {High-resolution functional imaging of neural activity in vivo relies on appropriate labeling methods. In this issue of Neuron, Nagayama et al. introduce a simple procedure for staining subsets of neurons with organic calcium indicator dyes via local electroporation. Neuronal populations are sparsely labeled, preserving the ability to resolve calcium signals in dendrites and synaptic structures.}, Author = {Helmchen, Fritjof and Nevian, Thomas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Staining and Labeling;21 Neurophysiology;Fluorescent Dyes;Diagnostic Imaging;Calcium;comment;Animals;Brain;24 Pubmed search results 2008;Neurons}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Neurophysiology, Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland. helmchen\@hifo.unizh.ch}, Pages = {771-3}, Pii = {S0896-6273(07)00149-3}, Pubmed = {17359911}, Title = {Little strokes fill big oaks: a simple in vivo stain of brain cells}, Uuid = {CA91B9FD-EF2D-4B5A-9582-E39B4D02D572}, Volume = {53}, Year = {2007}, url = {papers/Helmchen_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.03.001}} @article{Hematti:2004, Abstract = {Murine leukemia virus (MLV)-derived vectors are widely used for hematopoietic stem cell (HSC) gene transfer, but lentiviral vectors such as the simian immunodeficiency virus (SIV) may allow higher efficiency transfer and better expression. Recent studies in cell lines have challenged the notion that retroviruses and retroviral vectors integrate randomly into their host genome. Medical applications using these vectors are aimed at HSCs, and thus large-scale comprehensive analysis of MLV and SIV integration in long-term repopulating HSCs is crucial to help develop improved integrating vectors. We studied integration sites in HSCs of rhesus monkeys that had been transplanted 6 mo to 6 y prior with MLV- or SIV-transduced CD34(+)cells. Unique MLV (491) and SIV (501) insertions were compared to a set of in silico-generated random integration sites. While MLV integrants were located predominantly around transcription start sites, SIV integrants strongly favored transcription units and gene-dense regions of the genome. These integration patterns suggest different mechanisms for integration as well as distinct safety implications for MLV versus SIV vectors.}, Author = {Hematti, Peiman and Hong, Bum-Kee K. and Ferguson, Cole and Adler, Rima and Hanawa, Hideki and Sellers, Stephanie and Holt, Ingeborg E. and Eckfeldt, Craig E. and Sharma, Yugal and Schmidt, Manfred and von Kalle, Christof and Persons, Derek A. and Billings, Eric M. and Verfaillie, Catherine M. and Nienhuis, Arthur W. and Wolfsberg, Tyra G. and Dunbar, Cynthia E. and Calmels, Boris}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {22 Stem cells;15 Retrovirus mechanism;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {101183755}, Number = {12}, Organization = {Hematology Branch, National Institutes of Health Bethesda, Maryland, USA.}, Pages = {e423}, Pubmed = {15550989}, Title = {Distinct genomic integration of MLV and SIV vectors in primate hematopoietic stem and progenitor cells}, Uuid = {C0683DDD-2CD5-4D37-B0E6-28F6B8DCC085}, Volume = {2}, Year = {2004}, url = {papers/Hematti_PLoSBiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0020423}} @article{Hempel:2007, Abstract = {Sorting of fluorescent cells is a powerful technique for revealing the cellular processes that differ among the various cell types found in complex tissues. With the recent availability of transgenic mouse strains in which specific subpopulations of neurons are labeled, it has become desirable to purify these fluorescent neurons from their surrounding hetereogeneous brain tissue for electrophysiological, biochemical and molecular analyses. This has been accomplished using automated fluorescence-activated cell sorting (FACS) and laser capture microdissection (LCM). Although these procedures can be effective, they have some serious disadvantages, including high equipment costs and difficulty in obtaining samples completely free of contaminating tissue. Here we offer an alternative protocol for purifying fluorescent neurons, which relies on less-expensive equipment, readily produces perfectly pure samples and can be applied to neurons that are only dimly labeled and present in low numbers. The entire protocol can be completed in 3-5 h.}, Author = {Hempel, Chris M. and Sugino, Ken and Nelson, Sacha B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1750-2799}, Journal = {Nat Protoc}, Keywords = {24 Pubmed search results 2008}, Nlm_Id = {101284307}, Number = {11}, Organization = {Department of Biology and National Center for Behavioral Genomics, Brandeis University, MS 008, 415 South Street, Waltham, Massachusetts 02454-9110, USA.}, Pages = {2924-9}, Pii = {nprot.2007.416}, Pubmed = {18007629}, Title = {A manual method for the purification of fluorescently labeled neurons from the mammalian brain}, Uuid = {DAF6E242-CAEE-4678-96A2-7DAD44291983}, Volume = {2}, Year = {2007}, url = {papers/Hempel_NatProtoc2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nprot.2007.416}} @article{Hendel:2008, Abstract = {Recent advance in the design of genetically encoded calcium indicators (GECIs) has further increased their potential for direct measurements of activity in intact neural circuits. However, a quantitative analysis of their fluorescence changes (DeltaF) in vivo and the relationship to the underlying neural activity and changes in intracellular calcium concentration (Delta[Ca(2+)](i)) has not been given. We used two-photon microscopy, microinjection of synthetic Ca(2+) dyes and in vivo calibration of Oregon-Green-BAPTA-1 (OGB-1) to estimate [Ca(2+)](i) at rest and Delta[Ca(2+)](i) at different action potential frequencies in presynaptic motoneuron boutons of transgenic Drosophila larvae. We calibrated DeltaF of eight different GECIs in vivo to neural activity, Delta[Ca(2+)](i), and DeltaF of purified GECI protein at similar Delta[Ca(2+)] in vitro. Yellow Cameleon 3.60 (YC3.60), YC2.60, D3cpv, and TN-XL exhibited twofold higher maximum DeltaF compared with YC3.3 and TN-L15 in vivo. Maximum DeltaF of GCaMP2 and GCaMP1.6 were almost identical. Small Delta[Ca(2+)](i) were reported best by YC3.60, D3cpv, and YC2.60. The kinetics of Delta[Ca(2+)](i) was massively distorted by all GECIs, with YC2.60 showing the slowest kinetics, whereas TN-XL exhibited the fastest decay. Single spikes were only reported by OGB-1; all GECIs were blind for Delta[Ca(2+)](i) associated with single action potentials. YC3.60 and D3cpv tentatively reported spike doublets. In vivo, the K(D) (dissociation constant) of all GECIs was shifted toward lower values, the Hill coefficient was changed, and the maximum DeltaF was reduced. The latter could be attributed to resting [Ca(2+)](i) and the optical filters of the equipment. These results suggest increased sensitivity of new GECIs but still slow on rates for calcium binding.}, Author = {Hendel, Thomas and Mank, Marco and Schnell, Bettina and Griesbeck, Oliver and Borst, Alexander and Reiff, Dierk F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Presynaptic Terminals;Calcium Signaling;Animals;Aniline Compounds;comparative study;Spectrometry, Fluorescence;Fluoresceins;Female;Animals, Genetically Modified;Calcium;research support, non-u.s. gov't;Male;Intracellular Fluid;Action Potentials;Neurons;Microscopy, Fluorescence, Multiphoton;Drosophila;24 Pubmed search results 2008;Models, Neurological;Drosophila Proteins;optical physiology;optical imaging;calcium imaging;frontiers review}, Month = {7}, Nlm_Id = {8102140}, Number = {29}, Organization = {Department of Systems and Computational Neurobiology, Max Planck Institute of Neurobiology, D-82152 Martinsried, Germany.}, Pages = {7399-411}, Pii = {28/29/7399}, Pubmed = {18632944}, Title = {Fluorescence changes of genetic calcium indicators and OGB-1 correlated with neural activity and calcium in vivo and in vitro}, Uuid = {CEEE574B-A51D-40A2-82AD-B8BC3F682062}, Volume = {28}, Year = {2008}, url = {papers/Hendel_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1038-08.2008}} @article{Hengartner:2000, Abstract = {Apoptosis--the regulated destruction of a cell--is a complicated process. The decision to die cannot be taken lightly, and the activity of many genes influence a cell's likelihood of activating its self- destruction programme. Once the decision is taken, proper execution of the apoptotic programme requires the coordinated activation and execution of multiple subprogrammes. Here I review the basic components of the death machinery, describe how they interact to regulate apoptosis in a coordinated manner, and discuss the main pathways that are used to activate cell death.}, Author = {Hengartner, M. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Nature}, Keywords = {E-11;07 Excitotoxicity Apoptosis;Human;*Apoptosis;Mitochondria/physiology;Animal;Caspases/metabolism}, Number = {6805}, Organization = {Cold Spring Harbor Laboratory, New York 11724, USA. hengartn\@cshl.org}, Pages = {770-6.}, Title = {The biochemistry of apoptosis}, Uuid = {7FFC9FEF-E4A4-4D8C-AB0E-1C876C471CD8}, Volume = {407}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11048727}} @article{Henion:2005, Abstract = {During embryonic development, axons from sensory neurons in the olfactory epithelium (OE) extend into the olfactory bulb (OB) where they synapse with projection neurons and form glomerular structures. To determine whether glycans play a role in these processes, we analyzed mice deficient for the glycosyltransferase beta1,3-N-acetylglucosaminyltransferase 1 (beta3GnT1), a key enzyme in lactosamine glycan synthesis. Terminal lactosamine expression, as shown by immunoreactivity with the monoclonal antibody 1B2, is dramatically reduced in the neonatal null OE. Postnatal beta3GnT1-/- mice exhibit severely disorganized OB innervation and defective glomerular formation. Beginning in embryonic development, specific subsets of odorant receptor-expressing neurons are progressively lost from the OE of null mice, which exhibit a postnatal smell perception deficit. Axon guidance errors and increased neuronal cell death result in an absence of P2, I7, and M72 glomeruli, indicating a reduction in the repertoire of odorant receptor-specific glomeruli. By approximately 2 weeks of age, lactosamine is unexpectedly reexpressed in sensory neurons of null mice through a secondary pathway, which is accompanied by the regrowth of axons into the OB glomerular layer and the return of smell perception. Thus, both neonatal OE degeneration and the postnatal regeneration are lactosamine dependent. Lactosamine expression in beta3GnT1-/- mice is also reduced in pheromone-receptive vomeronasal neurons and dorsal root ganglion cells, suggesting that beta3GnT1 may perform a conserved function in multiple sensory systems. These results reveal an essential role for lactosamine in sensory axon pathfinding and in the formation of OB synaptic connections.}, Author = {Henion, Timothy R. and Raitcheva, Denitza and Grosholz, Robert and Biellmann, Franziska and Skarnes, William C. and Hennet, Thierry and Schwarting, Gerald A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8102140}, Number = {8}, Organization = {Shriver Center, Waltham, Massachusetts 02452, USA.}, Pages = {1894-903}, Pii = {25/8/1894}, Pubmed = {15728829}, Title = {Beta1,3-N-acetylglucosaminyltransferase 1 glycosylation is required for axon pathfinding by olfactory sensory neurons}, Uuid = {B0D745DB-3AB6-48F1-BF9C-769F912D0D31}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4654-04.2005}} @article{Hensch:2005, Abstract = {Neuronal circuits in the brain are shaped by experience during 'critical periods' in early postnatal life. In the primary visual cortex, this activity-dependent development is triggered by the functional maturation of local inhibitory connections and driven by a specific, late-developing subset of interneurons. Ultimately, the structural consolidation of competing sensory inputs is mediated by a proteolytic reorganization of the extracellular matrix that occurs only during the critical period. The reactivation of this process, and subsequent recovery of function in conditions such as amblyopia, can now be studied with realistic circuit models that might generalize across systems.}, Author = {Hensch, Takao K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Peptide Hydrolases;Synapses;24 Pubmed search results 2008;21 Neurophysiology;Critical Period (Psychology);Neuronal Plasticity;Models, Neurological;Neural Pathways;Time Factors;21 Activity-development;gamma-Aminobutyric Acid;Animals;Brain;Cerebral Cortex;review;Humans}, Month = {11}, Nlm_Id = {100962781}, Number = {11}, Organization = {RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama, 351-0198, Japan. hensch\@riken.jp}, Pages = {877-88}, Pii = {nrn1787}, Pubmed = {16261181}, Title = {Critical period plasticity in local cortical circuits}, Uuid = {9CAB9E7F-C179-4EE8-B949-74131BFF2200}, Volume = {6}, Year = {2005}, url = {papers/Hensch_NatRevNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1787}} @article{Hensch:1998, Abstract = {Sensory experience in early life shapes the mammalian brain. An impairment in the activity-dependent refinement of functional connections within developing visual cortex was identified here in a mouse model. Gene-targeted disruption of one isoform of glutamic acid decarboxylase prevented the competitive loss of responsiveness to an eye briefly deprived of vision, without affecting cooperative mechanisms of synapse modification in vitro. Selective, use-dependent enhancement of fast intracortical inhibitory transmission with benzodiazepines restored plasticity in vivo, rescuing the genetic defect. Specific networks of inhibitory interneurons intrinsic to visual cortex may detect perturbations in sensory input to drive experience-dependent plasticity during development.}, Author = {Hensch, T. K. and Fagiolini, M. and Mataga, N. and Stryker, M. P. and Baekkeskov, S. and Kash, S. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {gamma-Aminobutyric Acid;Long-Term Potentiation;Diazepam;Animals;Photic Stimulation;Gene Targeting;Neuronal Plasticity;Synaptic Transmission;Visual Pathways;Mice, Inbred C57BL;Receptors, GABA-A;Mice, Knockout;21 Neurophysiology;Glutamate Decarboxylase;Mice;Interneurons;GABA Modulators;24 Pubmed search results 2008;Visual Cortex}, Month = {11}, Nlm_Id = {0404511}, Number = {5393}, Organization = {Laboratory for Neuronal Circuit Development, Brain Science Institute RIKEN, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. hensch\@postman.riken.go.jp}, Pages = {1504-8}, Pubmed = {9822384}, Title = {Local GABA circuit control of experience-dependent plasticity in developing visual cortex}, Uuid = {A0EE9598-1793-4ED2-9D6F-DD31CF93720E}, Volume = {282}, Year = {1998}, url = {papers/Hensch_Science1998.pdf}} @article{Hensch:2004, Abstract = {The mammalian visual cortex is organized into columns. Here, we examine cortical influences upon developing visual afferents in the cat by altering intrinsic gamma-aminobutyric acid (GABA)-mediated inhibition with benzodiazepines. Local enhancement by agonist (diazepam) infusion did not perturb visual responsiveness, but did widen column spacing. An inverse agonist (DMCM) produced the opposite effect. Thus, intracortical inhibitory circuits shape the geometry of incoming thalamic arbors, suggesting that cortical columnar architecture depends on neuronal activity.}, Author = {Hensch, Takao K. and Stryker, Michael P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Diazepam;gamma-Aminobutyric Acid;Electrophysiology;Photic Stimulation;Animals;Synaptic Transmission;Visual Pathways;Carbolines;research support, non-u.s. gov't;Vision;Thalamus;Receptors, GABA-A;research support, u.s. gov't, p.h.s.;Neurons;21 Neurophysiology;24 Pubmed search results 2008;Dominance, Ocular;Visual Cortex;Cats;Neural Inhibition}, Month = {3}, Nlm_Id = {0404511}, Number = {5664}, Organization = {Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan. hensch\@postman.riken}, Pages = {1678-81}, Pii = {303/5664/1678}, Pubmed = {15017001}, Title = {Columnar architecture sculpted by GABA circuits in developing cat visual cortex}, Uuid = {609F5C59-6DF3-4A90-B173-8021162176F9}, Volume = {303}, Year = {2004}, url = {papers/Hensch_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1091031}} @article{Henschler:2004, Abstract = {To study the homing behaviour of an enriched multipotent primitive haemopoietic progenitor cell (HPC) population in mice, undifferentiated murine factor-dependent multipotent HPCs (FDCP-mix), stably transfected with the green fluorescence protein gene, were intravenously injected into congenic mice. After 2 or 24 h, cell suspensions were prepared from bone marrow, spleen, lung, liver, muscle, colon, kidney, brain or blood of the mice and analysed by flow cytometry. Using direct quantifiable determination of total HPC numbers homed per organ and a method to estimate the degree of organ contamination by HPC that were present in blood vessels within the organs before preparation, the highest absolute numbers of HPC were detected in the liver and lungs at 2 h but this was sharply decreased at 24 h, whereas HPC selectively accumulated in the bone marrow and spleen at 24 h after transplantation. Only a few HPC were detected in other organs. The seeding efficiency of homed FDCP-mix HPC to the bone marrow and spleen was approximately 1.5\%and ranged between that of primary whole bone marrow cells and lineage-depleted freshly isolated bone marrow cells. Pretreatment of HPC with inhibitors of signal transduction indicated that short-term homing of multipotent HPC into haemopoietic organs is an active process requiring co-ordinated intracellular signalling through Rho family small GTPases and protein kinases. Thus, short-term homing of FDCP-mix HPC into haemopoietic organs is of low efficiency but high selectivity, and provides a system to analyse the mechanisms and manipulation of primitive HPC which saves large numbers of donor animals.}, Author = {Henschler, R. and Fehervizyova, Z. and Bistrian, R. and Seifried, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0007-1048}, Journal = {Br J Haematol}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Transfection;Multipotent Stem Cells;Cell Count;Cell Movement;Liver;Mice, Inbred C57BL;11 Glia;Time Factors;Green Fluorescent Proteins;Bone Marrow Cells;Mice, Inbred DBA;Flow Cytometry;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Models, Animal;Spleen;Lung}, Month = {7}, Nlm_Id = {0372544}, Number = {1}, Organization = {Institute of Transfusion Medicine and Immune Haematology, German Red Cross Blood Centre, Frankfurt, Germany. rhenschler\@bsdhessen.de}, Pages = {111-9}, Pii = {BJH4995}, Pubmed = {15198741}, Title = {A mouse model to study organ homing behaviour of haemopoietic progenitor cells reveals high selectivity but low efficiency of multipotent progenitors to home into haemopoietic organs}, Uuid = {9D0ABAE4-32CD-4606-B86C-E43871B925F8}, Volume = {126}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1365-2141.2004.04995.x}} @article{Henske:1996, Abstract = {Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by seizures, mental retardation, and hamartomatous lesions. Although hamartomas can occur in almost any organ, they are most common in the brain, kidney, heart, and skin. Allelic loss or loss of heterozygosity (LOH) in TSC lesions has previously been reported on chromosomes 16p13 and 9q34, the locations of the TSC2 and TSC1 genes, respectively, suggesting that the TSC genes act as tumor-suppressor genes. In our study, 87 lesions from 47 TSC patients were analyzed for LOH in the TSC1 and TSC2 chromosomal regions. Three findings resulted from this analysis. First, we confirmed that the TSC1 critical region is distal to D9S149. Second, we found LOH more frequently on chromosome 16p13 than on 9q34. Of the 28 patients with angiomyolipomas or rhabdomyomas, 16p13 LOH was detected in lesions from 12 (57\%) of 21 informative patients, while 9q34 LOH was detected in lesions from only 1 patient (4\%). This could indicate that TSC2 tumors are more likely than TSC1 tumors to require surgical resection or that TSC2 is more common than TSC1 in our patient population. It is also possible that small regions of 9q34 LOH were missed. Lastly, LOH was found in 56\%of renal angiomyolipomas and cardiac rhabdomyormas but in only 4\%of TSC brain lesions. This suggests that brain lesions can result from different pathogenic mechanisms than kidney and heart lesions.}, Author = {Henske, E. P. and Scheithauer, B. W. and Short, M. P. and Wollmann, R. and Nahmias, J. and Hornigold, N. and van Slegtenhorst, M. and Welsh, C. T. and Kwiatkowski, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0002-9297}, Journal = {Am J Hum Genet}, Keywords = {10 Development;Heterozygote;Chromosomes, Human, Pair 16;Kidney;Base Sequence;comparative study;Humans;Tuberous Sclerosis;Brain;Chromosome Deletion;research support, non-u.s. gov't;Angiomyolipoma;Chromosomes, Human, Pair 9;Alleles;10 genetics malformation;research support, u.s. gov't, p.h.s.;Rhabdomyoma;24 Pubmed search results 2008;Molecular Sequence Data}, Month = {8}, Nlm_Id = {0370475}, Number = {2}, Organization = {Experimental Medicine Division, Brigham and Women's Hospital, Boston, MA 02115, USA.}, Pages = {400-6}, Pubmed = {8755927}, Title = {Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions}, Uuid = {B0AD6056-680F-4F8E-AA1D-58D0DDFA4CA8}, Volume = {59}, Year = {1996}} @article{Henze:2000, Abstract = {Multichannel tetrode array recording in awake behaving animals provides a powerful method to record the activity of large numbers of neurons. The power of this method could be extended if further information concerning the intracellular state of the neurons could be extracted from the extracellularly recorded signals. Toward this end, we have simultaneously recorded intracellular and extracellular signals from hippocampal CA1 pyramidal cells and interneurons in the anesthetized rat. We found that several intracellular parameters can be deduced from extracellular spike waveforms. The width of the intracellular action potential is defined precisely by distinct points on the extracellular spike. Amplitude changes of the intracellular action potential are reflected by changes in the amplitude of the initial negative phase of the extracellular spike, and these amplitude changes are dependent on the state of the network. In addition, intracellular recordings from dendrites with simultaneous extracellular recordings from the soma indicate that, on average, action potentials are initiated in the perisomatic region and propagate to the dendrites at 1.68 m/s. Finally we determined that a tetrode in hippocampal area CA1 theoretically should be able to record electrical signals from approximately 1, 000 neurons. Of these, 60-100 neurons should generate spikes of sufficient amplitude to be detectable from the noise and to allow for their separation using current spatial clustering methods. This theoretical maximum is in contrast to the approximately six units that are usually detected per tetrode. From this, we conclude that a large percentage of hippocampal CA1 pyramidal cells are silent in any given behavioral condition.}, Author = {Henze, D. A. and Borhegyi, Z. and Csicsvari, J. and Mamiya, A. and Harris, K. D. and Buzs{\'a}ki, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Extracellular Space;research support, non-u.s. gov't;Dendrites;21 Neurophysiology;Rats, Sprague-Dawley;Sleep, REM;Action Potentials;Hippocampus;Pyramidal Cells;Rats;Stereotaxic Techniques;Electrophysiology;research support, u.s. gov't, p.h.s.;Animals;24 Pubmed search results 2008;Microelectrodes}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA. buzsaki\@axon.rutgers.edu}, Pages = {390-400}, Pubmed = {10899213}, Title = {Intracellular features predicted by extracellular recordings in the hippocampus in vivo}, Uuid = {C7AFB5AF-2434-4C8C-9CFB-A013A159F25F}, Volume = {84}, Year = {2000}, url = {papers/Henze_JNeurophysiol2000.pdf}} @article{Heppner:2005a, Abstract = {Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo.}, Author = {Heppner, Frank L. and Greter, Melanie and Marino, Denis and Falsig, Jeppe and Raivich, Gennadij and H{\"o}velmeyer, Nadine and Waisman, Ari and R{\"u}licke, Thomas and Prinz, Marco and Priller, Josef and Becher, Burkhard and Aguzzi, Adriano}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {11 Glia}, Month = {2}, Nlm_Id = {9502015}, Number = {2}, Organization = {Institute of Neuropathology, University Hospital Zurich, CH-8091 Zurich, Switzerland.}, Pages = {146-52}, Pii = {nm1177}, Pubmed = {15665833}, Title = {Experimental autoimmune encephalomyelitis repressed by microglial paralysis}, Uuid = {27249648-1844-4841-AB32-C381AAA67E96}, Volume = {11}, Year = {2005}, url = {papers/Heppner_NatMed2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm1177}} @article{Heppner:2005, Author = {Heppner, F. L. and Greter, M. and Marino, D. and Falsig, J. and Raivich, G. and H{\"o}velmeyer, N. and Waisman, A. and R{\"u}licke, T. and Prinz, M. and Priller, J. and Becher, B. and Aguzzi, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {11 Glia}, Month = {4}, Nlm_Id = {9502015}, Number = {4}, Pages = {455}, Pii = {nm0405-455}, Pubmed = {15812520}, Title = {CORRIGENDUM: Experimental autoimmune encephalomyelitis repressed by microglial paralysis}, Uuid = {EEF0B380-A984-439B-858C-F2221609F477}, Volume = {11}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm0405-455}} @article{Herculano-Houzel:2006, Abstract = {How do cell number and size determine brain size? Here, we show that, in the order Rodentia, increased size of the cerebral cortex, cerebellum, and remaining areas across six species is achieved through greater numbers of neurons of larger size, and much greater numbers of nonneuronal cells of roughly invariant size, such that the ratio between total neuronal and nonneuronal mass remains constant across species. Although relative cerebellar size remains stable among rodents, the number of cerebellar neurons increases with brain size more rapidly than in the cortex, such that the cerebellar fraction of total brain neurons increases with brain size. In contrast, although the relative cortical size increases with total brain size, the cortical fraction of total brain neurons remains constant. We propose that the faster increase in average neuronal size in the cerebral cortex than in the cerebellum as these structures gain neurons and the rapidly increasing glial numbers that generate glial mass to match total neuronal mass at a fixed glia/neuron total mass ratio are fundamental cellular constraints that lead to the relative expansion of cerebral cortical volume across species.}, Author = {Herculano-Houzel, Suzana and Mota, Bruno and Lent, Roberto}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008;19 Neocortical evolution}, Month = {8}, Nlm_Id = {7505876}, Number = {32}, Organization = {Departamento de Anatomia, Instituto de Ci\^{e}ncias Biom{\'e}dicas, Universidade Federal do Rio de Janeiro, 21941-590, Rio de Janeiro, Brazil. suzanahh\@ism.com.br}, Pages = {12138-43}, Pii = {0604911103}, Pubmed = {16880386}, Title = {Cellular scaling rules for rodent brains}, Uuid = {5E7A0EC4-47CB-486D-A9CF-BE161643FBA3}, Volume = {103}, Year = {2006}, url = {papers/Herculano-Houzel_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0604911103}} @article{Herman:1994, Abstract = {0301-0082 Journal Article Review Review, Academic}, Author = {Herman, J. P. and Abrous, N. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Prog Neurobiol}, Keywords = {Corpus Striatum/physiology;17 Transplant Regeneration;Homeostasis;Human;Neuronal Plasticity;L abstr;Dopamine/*physiology;Brain Tissue Transplantation/*physiology;Receptors, Dopamine/physiology;Motor Activity;Animals;Support, Non-U.S. Gov't;Neurons/physiology/*transplantation/ultrastructure;Mesencephalon/physiology}, Number = {1}, Organization = {CNRS UMR 9941, Laboratoire des Interactions Cellulaires Neuroendocriniennes, Faculte de Medecine Nord, Marseille, France.}, Pages = {1-35}, Pubmed = {7831470}, Title = {Dopaminergic neural grafts after fifteen years: results and perspectives}, Uuid = {83C31F35-4395-45F2-A9A9-2298A1D82374}, Volume = {44}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7831470}} @article{Hermanson:2002, Abstract = {Understanding the gene programmes that regulate maintenance and differentiation of neural stem cells is a central question in stem cell biology. Virtually all neural stem cells maintain an undifferentiated state and the capacity to self-renew in response to fibroblast growth factor-2 (FGF2). Here we report that a repressor of transcription, the nuclear receptor co-repressor (N-CoR), is a principal regulator in neural stem cells, as FGF2-treated embryonic cortical progenitors from N-CoR gene-disrupted mice display impaired self-renewal and spontaneous differentiation into astroglia-like cells. Stimulation of wild-type neural stem cells with ciliary neurotrophic factor (CNTF), a differentiation-inducing cytokine, results in phosphatidylinositol-3-OH kinase/Akt1 kinase-dependent phosphorylation of N-CoR, and causes a temporally correlated redistribution of N-CoR to the cytoplasm. We find that this is a critical strategy for cytokine-induced astroglia differentiation and lineage-characteristic gene expression. Recruitment of protein phosphatase-1 to a specific binding site on N-CoR exerts a reciprocal effect on the cellular localization of N-CoR. We propose that repression by N-CoR, modulated by opposing enzymatic activities, is a critical mechanism in neural stem cells that underlies the inhibition of glial differentiation. 0028-0836 Journal Article}, Author = {Hermanson, O. and Jepsen, K. and Rosenfeld, M. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:48 -0400}, Journal = {Nature}, Keywords = {Human;Chromatin/metabolism;Animals;Enzyme Activation;1-Phosphatidylinositol 3-Kinase/metabolism;Protein-Serine-Threonine Kinases/metabolism;Stem Cells/*cytology/drug effects/enzymology/metabolism;Protein Transport;11 Glia;Phosphoprotein Phosphatase/antagonists &inhibitors/metabolism;Cell Line;Support, Non-U.S. Gov't;Ciliary Neurotrophic Factor/pharmacology;*Cell Differentiation/drug effects;Phosphorylation/drug effects;Astrocytes/*cytology/drug effects/enzymology/metabolism;Cytoplasm/metabolism;Repressor Proteins/*metabolism;Fibroblast Growth Factor 2/pharmacology;Support, U.S. Gov't, P.H.S.;Nuclear Proteins/*metabolism;Cell Nucleus/metabolism;Neurons/*cytology/drug effects/enzymology/metabolism;Mice;Cell Division/drug effects;G pdf}, Number = {6910}, Organization = {Howard Hughes Medical Institute, Department of Molecular Medicine, University of California, San Diego, School of Medicine, 9500 Gilman Drive, Room 345, La Jolla, California 92093-0648, USA.}, Pages = {934-9}, Title = {N-CoR controls differentiation of neural stem cells into astrocytes}, Uuid = {014877D0-8701-43CA-9E16-2DBCA8F78DBC}, Volume = {419}, Year = {2002}, url = {papers/Hermanson_Nature2002.pdf}} @article{Hernandez:1996, Abstract = {Significant progress has been made in elucidating the mechanisms of viral membrane fusion proteins; both those that function at low, as well as those that function at neutral, pH. For many viral fusion proteins evidence now suggests that a triggered conformational change that exposes a previously cryptic fusion peptide, along with a rearrangement of the fusion protein oligomer, allows the fusion peptide to gain access to the target bilayer and thus initiate the fusion reaction. Although the topologically equivalent process of cell-cell fusion is less well understood, several cell surface proteins, including members of the newly described ADAM gene family, have emerged as candidate adhesion/fusion proteins.}, Author = {Hernandez, L. D. and Hoffman, L. R. and Wolfsberg, T. G. and White, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Issn = {1081-0706}, Journal = {Annu Rev Cell Dev Biol}, Keywords = {Cell Membrane;Viral Fusion Proteins;Recombinant Fusion Proteins;Membrane Fusion;08 Aberrant cell cycle;Viruses;review, tutorial;15 Retrovirus mechanism;24 Pubmed search results 2008;review}, Medline = {97125667}, Nlm_Id = {9600627}, Organization = {Department of Cell Biology, University of Virginia, Charlottesville 22908, USA.}, Pages = {627-61}, Pubmed = {8970739}, Title = {Virus-cell and cell-cell fusion}, Uuid = {33DA7E2C-216C-11DB-96D3-000D9346EC2A}, Volume = {12}, Year = {1996}, url = {papers/Hernandez_AnnuRevCellDevBiol1996.pdf}} @article{Hernit-Grant:1996, Abstract = {In the neocortex, the effectiveness of potential transplantation therapy for diseases involving neuronal loss may depend upon whether donor neurons can reestablish the precise long-distance projections that form the basis of sensory, motor, and cognitive function. During corticogenesis, the formation of these connections is affected by tropic factors, extracellular matrix, structural pathways, and developmental cell death. Previous studies demonstrated that embryonic neurons and multipotent neural precursors transplanted into neocortex or mice undergoing photolytically induced, synchronous, apoptotic neuronal degeneration selectively migrate into these regions, where they differentiate into pyramidal neurons and accept afferent synaptic input. The experiments presented here assess whether embryonic neurons transplanted into regions of somatosensory cortex undergoing targeted cell death differentiate further and develop long-distance axons and whether this outgrowth is target specific. Neocortical neurons from Gestational Day 17 mouse embryos were dissociated, prelabeled with fluorescent nanospheres and a lipophilic dye (DiI or PKH), and transplanted into adult mouse primary somatosensory cortex (S1) undergoing apoptotic degeneration of callosal projection neurons. Donor neurons selectively migrated into and differentiated within regions of targeted neuronal death in lamina II/III over a 2-week period, in agreement with our prior studies. To detect possible projections made by donor neurons 2, 4, 6, 8, or 10 weeks following transplantation, the retrogradely transported dye fluorogold (FG) was stereotaxically injected into contralateral S1, ipsilateral secondary somatosensory cortex (S2), or ipsilateral thalamus. Ten weeks following transplantation, 21 +/- 5\%of the labeled donor neurons were labeled by FG injections into contralateral S1, demonstrating that donor neurons sent projections to the distant area, the original target of host neurons undergoing photolytically induced cell death. No donor neurons were labeled with FG injections into ipsilateral S2 or thalamus, nearby targets of other subpopulations of neurons in S1. These data indicate that in the adult neocortex: (1) transplanted immature neurons are capable of extending long-distance projections between hemispheres through the mature white matter of the corpus callosum and (2) these projections are formed with specificity to replace projections by neurons undergoing synchronous degeneration. These experiments provide an experimental system with which to test factors affecting such outgrowth and connectivity. Taken together, these results suggest that the reconstruction and repair of cortical circuitry responsible for sensory, motor, or cognitive function may be possible in the mature neocortex, if donor neurons or precursor cells are provided with the correct combination of local and distant signals within an appropriately permissive host environment. 0014-4886 Journal Article}, Author = {Hernit-Grant, C. S. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Exp Neurol}, Keywords = {Neurons/cytology/*transplantation;Mice;Fetal Tissue Transplantation;Cell Division/physiology;17 Transplant Regeneration;Photochemistry;L abstr;Neural Pathways;Mice, Inbred C57BL;Cell Death/physiology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't;Somatosensory Cortex/*cytology;Age Factors;Corpus Callosum/*cytology}, Number = {1}, Organization = {Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {131-42}, Pubmed = {8635560}, Title = {Embryonic neurons transplanted to regions of targeted photolytic cell death in adult mouse somatosensory cortex re-form specific callosal projections}, Uuid = {8756E0BE-EC7F-11DA-8605-000D9346EC2A}, Volume = {139}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8635560}} @article{Herrera:1999, Abstract = {Neural stem cells persist in the adult brain subventricular zone (SVZ). These cells generate a large number of new neurons that migrate to the olfactory bulb, where they complete their differentiation. Here, we transplanted cells carrying beta-galactosidase under the control of neuron-specific enolase promoter (NSE::LacZ) from the SVZ of adult mice into the striatum cortex and olfactory bulb, with or without an excitotoxin lesion. Between 2 and 8 weeks after transplantation, grafted cells were present in the recipient regions, but extensive migration and differentiation into mature neurons of grafted cells were only observed in the olfactory bulb. Clusters of graft-derived neuroblasts forming chain-like structures were observed within or close to the grated sites in the cortex and striatum; electron microscopy confirmed that graft-derived cells in the olfactory bulb and a small number in the striatum were neurons. Surprisingly, most of the cells expressing NSE::LacZ outside the olfactory bulb were astrocytes. We conclude that primary precursors from the SVZ migrate and differentiate effectively only within the environment of the olfactory bulb. Only limited survival and differentiation were observed in other brain regions studied. 1st report showing that differentiation potential of postnatal svz precursors when transplanted into adult brain is largely limited to the astroglial fate.}, Author = {Herrera, D. G. and Garcia-Verdugo, J. M. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {Ann Neurol}, Keywords = {Lateral Ventricles/*cytology;Transfection;Kainic Acid/toxicity;Corpus Striatum/*cytology/drug effects;Animal;02 Adult neurogenesis migration;Transplantation, Heterotopic;beta-Galactosidase/genetics;Stem Cells/*cytology;Male;B-19;Cerebral Cortex/*cytology/drug effects;Recombinant Proteins/metabolism;Phosphopyruvate Hydratase/genetics;Transplantation, Isogeneic;Neurons/*cytology/*transplantation/ultrastructure;Support, U.S. Gov't, P.H.S.;Promoter Regions (Genetics);Brain Tissue Transplantation/*physiology;Mice;Olfactory Bulb/*cytology/drug effects}, Number = {6}, Organization = {Department of Psychiatry, The New York Hospital, Cornell Medical Center, NY, USA.}, Pages = {867-77.}, Title = {Adult-derived neural precursors transplanted into multiple regions in the adult brain}, Uuid = {523387C0-C4AF-4CEC-B4A5-3B07A8CBDCB8}, Volume = {46}, Year = {1999}, url = {papers/Herrera_AnnNeurol1999.pdf}} @article{Herrup:1995, Abstract = {Unexpected nerve cell death has been reported in several experimental situations where neurons have been forced to re-enter the cell cycle after leaving the ventricular zone and entering the G0, non-mitotic stage. To determine whether an association between cell death and unscheduled cell cycling might be found in conjunction with any naturally occurring developmental events, we have examined target-related cell death in two neuronal populations, the granule cells of the cerebellar cortex and the neurons of the inferior olive. Both of these cell populations have a demonstrated developmental dependency on their synaptic target, the cerebellar Purkinje cell. Two mouse neurological mutants, staggerer (sg/sg) and lurcher (+/Lc), are characterized by intrinsic Purkinje cell deficiencies and, in both mutants, substantial numbers of cerebellar granule cells and inferior olive neurons die due to the absence of trophic support from their main postsynaptic target. We report here that the levels of three independent cell cycle markers--cyclin D, proliferating cell nuclear antigen and bromodeoxyuridine incorporation--are elevated in the granule cells before they die. Although lurcher Purkinje cells die during a similar developmental period, no compelling evidence for any cell cycle involvement in this instance of pre-programmed cell death could be found. While application of the TUNEL technique (in situ terminal transferase end-labeling of fragmented DNA) failed to label dying granule cells in either mutant, light and electron microscopic observations are consistent with the interpretation that the death of these cells is apoptotic in nature. Together, the data indicate that target-related cell death in the developing central nervous system is associated with a mechanism of cell death that involves an apparent loss of cell cycle control. 0950-1991 Journal Article}, Author = {Herrup, K. and Busser, J. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {Development}, Keywords = {EE pdf;*Cell Cycle;Olivary Nucleus/cytology/embryology;Biological Markers;Neurons/cytology/*physiology;Cerebellar Cortex/cytology/embryology;Mice, Mutant Strains;Support, U.S. Gov't, P.H.S.;Fluorescent Antibody Technique;Animals;Mice;Apoptosis/*physiology;Purkinje Cells/cytology/*physiology}, Number = {8}, Organization = {Department of Neurology, Case Western Reserve Medical School, Cleveland, OH 44106, USA.}, Pages = {2385-95}, Pubmed = {7671804}, Title = {The induction of multiple cell cycle events precedes target-related neuronal death}, Uuid = {32527EC2-D395-11D9-A0E9-000D9346EC2A}, Volume = {121}, Year = {1995}, url = {papers/Herrup_Development1995.pdf}} @article{Herzog:1999, Abstract = {Although it has been known for over 50 years that olfactory receptor neuron (ORN) neurogenesis and subsequent reinnervation of the olfactory bulb (OB) occurs following ORN injury, the precise intrinsic and extrinsic factors that regulate this dynamic process have not yet been fully identified. In the first of two experiments, we characterized the time course of anatomical recovery following zinc sulfate (ZnSO(4)) lesion of ORNs in adult male Sprague-Dawley rats. ZnSO(4) produced a near complete deafferentation of OB within 3 days following intranasal administration. A time-dependent increase in ORN reinnervation of OB was observed following 10, 20, and 30 day recovery intervals. Given the evidence that bFGF, EGF, and TGF-alpha have mitogenic effects on ORNs in vitro, a second experiment examined the extent to which these growth factors (GFs) might enhance ORN regeneration and subsequent reinnervation of OB in vivo. Rats received intranasal infusions of ZnSO(4) on day 0, followed by subcutaneous injections of either bFGF (5, 10, or 50 microgram/kg), EGF (5, 10, or 50 microgram/kg), or TGF- alpha (5 or 10 microgram/kg) on days 3-6. Horseradish peroxidase (HRP) histochemistry of OB following a 10-day recovery period revealed a dose- related enhancement in reinnervation of OB for each of the three growth factors examined, with the greatest enhancement produced by TGF-alpha. These data suggest that GFs may regulate ORN mitogenesis in vivo in a way similar to that which has been characterized in vitro.}, Author = {Herzog, C. and Otto, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:23 -0400}, Journal = {Brain Res}, Keywords = {Nerve Regeneration/drug effects/*physiology;Olfactory Bulb/*physiology;Rats;Zinc Sulfate/administration &dosage/toxicity;Epidermal Growth Factor/*pharmacology;Animal;D pdf;Rats, Sprague-Dawley;Time Factors;Male;Transforming Growth Factor alpha/*pharmacology;Axonal Transport;Support, Non-U.S. Gov't;Nose;06 Adult neurogenesis injury induced;Horseradish Peroxidase;Infusions, Parenteral;Olfactory Receptor Neurons/cytology/drug effects/*physiology}, Number = {1-2}, Organization = {Program in Biopsychology and Behavioral Neuroscience, Department of Psychology, Rutgers University, New Brunswick, NJ, USA.}, Pages = {155-61.}, Title = {Regeneration of olfactory receptor neurons following chemical lesion: time course and enhancement with growth factor administration}, Uuid = {DEFCD029-3919-4613-B3A5-A1F6F459642D}, Volume = {849}, Year = {1999}, url = {papers/Herzog_BrainRes1999}} @article{Hess:2004, Abstract = {BACKGROUND: Bone marrow (BM)-derived cells differentiate into a wide variety of cell types. BM contains a heterogeneous population of stem and progenitor cells including hematopoietic stem cells, marrow stromal cells, and perhaps other progenitor cells. To establish unequivocally the transdifferentiation capability of a hematopoietic cell to a nonhematopoietic cell (endothelial cells, neurons, and glial cells), it is imperative to demonstrate that a single cell or clone of that single cell (clonal analysis) differentiates into cells comprising vessels or other cells in the brain. METHODS: We generated mice that exhibited a high level of hematopoietic reconstitution from a single enhanced green fluorescent protein (EGFP) stem cell. To achieve this, we combined FACS sorting and cell culture to generate a population of cells derived from a single hematopoietic stem cell (Lin-, CD34-, c-kit+, and Sca-1+). Clonal populations of cells were then transplanted into lethally irradiated recipient mice. After 3-4 months of engraftment, some mice underwent middle cerebral artery (MCA) suture occlusion. EGFP immunocytochemistry and dual labeling was performed with cell-specific markers on tissue from various time points. RESULTS: In all transplanted mice, EGFP+ highly ramified cells were seen in the brain parenchyma. These cells stained with RCA120 lectin and had the characteristics of parenchymal microglial cells. In brains without infarction and in uninfarcted brain regions of mice that underwent MCA occlusion, there were many EGFP+ cells in a perivascular distribution, associated with both small and larger blood vessels. The cells were tightly apposed to the vessel wall and some had long processes that enveloped the endothelial cells. After MCA occlusion, there was an influx of EGFP expressing cells in the ischemic tissue that colocalized with the "neovascularization." These EGFP+ cells were wrapped around endothelial cells in an albuminal location and did not coexpress von Willebrand Factor or CD31. We detected rare dual-labeled EGFP and NeuN-expressing cells. We detected two staining patterns. The more frequent pattern was phagocytosis of NeuN cells by EGFP expressing cells. However, we also detected rarer cells where the EGFP and NeuN appeared to be colocalized by confocal microscopy. CONCLUSIONS: HSC differentiate into parenchymal microglial cells and perivascular cells in the brain. The numbers of these cells increase after cerebral ischemia. The HSC is therefore one source of parenchymal microglial cells and a source for perivascular cells. After a cerebral infarction, there are rare HSC-derived cells that stain with the neuronal marker, NeuN. However, the more common pattern appears to represent phagocytosis of damaged neurons by EGFP+ microglial cells.}, Author = {Hess, David C. and Abe, Takanori and Hill, William D. and Studdard, Angeline Martin and Carothers, Jo and Masuya, Masahiro and Fleming, Paul A. and Drake, Christopher J. and Ogawa, Makio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cell Differentiation;Antigens, CD31;Phosphopyruvate Hydratase;Green Fluorescent Proteins;Alpha;Immunohistochemistry;Male;Antigens;Luminescent Proteins;Brain;Cells, Cultured;Carbocyanines;Plant Lectins;Animals;Flow Cytometry;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred C57BL;Hematopoietic Stem Cells;Research Support, U.S. Gov't, Non-P.H.S.;Endothelial Cells;11 Glia;Hematopoietic Stem Cell Transplantation;Laterality;Comparative Study;Radiation Chimera;Benzimidazoles;Time Factors;Female;Microglia;Endothelium, Vascular;Infarction, Middle Cerebral Artery;Microscopy, Confocal;Research Support, Non-U.S. Gov't;Hematopoiesis;Mice, Transgenic;Neurons;Mice}, Month = {4}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. dhess\@mail.mcg.edu}, Pages = {134-44}, Pii = {S0014488603005740}, Pubmed = {15026252}, Title = {Hematopoietic origin of microglial and perivascular cells in brain}, Uuid = {6E23815A-CEE1-11D9-B244-000D9346EC2A}, Volume = {186}, Year = {2004}, url = {papers/Hess_ExpNeurol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2003.11.005}} @article{Hess:2002, Abstract = {BACKGROUND AND PURPOSE: After an ischemic event, bone marrow-derived cells may be involved in reparative processes. There is increasing evidence that bone marrow-derived stem cells may be a source of endothelial cells and organ-specific cells. Our objectives were to determine whether bone marrow-derived cells were a source of endothelial cells and neurons after cerebral ischemia. METHODS: We transplanted bone marrow from male C57 BL/6-TgN (ACTbEGFP)1Osb mice, which express green fluorescent protein (GFP), into female C57 BL/6J mice. The recipient mice then underwent suture occlusion of the middle cerebral artery (MCA), and bone marrow- derived cells were tracked by GFP epifluorescence and Y chromosome probe. RESULTS: Within 3 days and at 7 and 14 days after MCA occlusion, bone marrow-derived cells incorporated into the vasculature in the ischemic zone and expressed an endothelial cell phenotype. Few bone marrow-derived cells incorporated into the vasculature 24 hours after MCA occlusion. Some bone marrow-derived cells also expressed the neuronal marker NeuN at 7 and 14 days after ischemia. CONCLUSIONS: Postnatal vasculogenesis occurs in the brain in the setting of a cerebral infarction. Bone marrow-derived cells are a source of endothelial cells and NeuN-expressing cells after cerebral infarction. This plasticity may be exploited in the future to enhance recovery after stroke.}, Author = {Hess, David C. and Hill, William D. and Martin-Studdard, Angeline and Carroll, James and Brailer, Joanna and Carothers, Jo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {1524-4628}, Journal = {Stroke}, Keywords = {Endothelium, Vascular;Cell Differentiation;Animals;Stem Cell Transplantation;Infarction, Middle Cerebral Artery;Bone Marrow Transplantation;Research Support, U.S. Gov't, Non-P.H.S.;Antigens, Differentiation;Female;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Microscopy, Fluorescence;Male;Radiation Chimera;Green Fluorescent Proteins;Disease Models, Animal;Neovascularization, Physiologic;Bone Marrow Cells;Neurons;Cerebrovascular Accident;Mice;Immunohistochemistry;Stem Cells;Luminescent Proteins;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {21984760}, Month = {5}, Nlm_Id = {0235266}, Number = {5}, Organization = {Department of Neurology, Medical College of Georgia, Augusta, Ga 30912, USA. dhess\@neuro.mcg.edu}, Pages = {1362-8}, Pubmed = {11988616}, Title = {Bone marrow as a source of endothelial cells and NeuN-expressing cells After stroke}, Uuid = {80D65F16-BAED-4A65-B54A-3E979A46D347}, Volume = {33}, Year = {2002}} @article{Hevner:2003, Abstract = {Cortical projection neurons exhibit diverse morphological, physiological, and molecular phenotypes, but it is unknown how many distinct types exist. Many projection cell phenotypes are associated with laminar fate (radial position), but each layer may also contain multiple types of projection cells. We have investigated two hypotheses: (1) that different projection cell types exhibit characteristic molecular expression profiles and (2) that laminar fates are determined primarily by molecular phenotype. We found that several transcription factors were differentially expressed by projection neurons, even within the same layer: Otx1 and Er81, for example, were expressed by different neurons in layer 5. Retrograde tracing showed that Er81 was expressed in corticospinal and corticocortical neurons. In contrast, Otx1 has been detected only in corticobulbar neurons [Weimann et al., Neuron 1999;24:819-831]. Birthdating demonstrated that different molecularly defined types were produced sequentially, in overlapping waves. Cells adopted laminar fates characteristic of their molecular phenotypes, regardless of cell birthday. Molecular markers also revealed the locations of different projection cell types in the malformed cortex of reeler mice. These studies suggest that molecular profiles can be used advantageously for classifying cortical projection cells, for analyzing their neurogenesis and fate specification, and for evaluating cortical malformations. 0378-5866 Journal Article}, Author = {Hevner, R. F. and Daza, R. A. and Rubenstein, J. L. and Stunnenberg, H. and Olavarria, J. F. and Englund, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {Dev Neurosci}, Keywords = {Pregnancy;10 Development;Brain/*embryology/*growth &development;Animals;Gene Expression Regulation, Developmental;Fluorescent Antibody Technique;Microscopy, Confocal;Female;Embryo and Fetal Development/*physiology;F pdf;Neurons/*classification/cytology/metabolism;Mice, Neurologic Mutants;Microscopy, Fluorescence;Embryo;Support, Non-U.S. Gov't;Transcription Factors/*biosynthesis;Pyramidal Cells/*cytology/metabolism;Animals, Newborn;Support, U.S. Gov't, P.H.S.;Mice;Bromodeoxyuridine;Biological Markers/analysis}, Number = {2-4}, Organization = {Department of Pathology, University of Washington, Harborview Medical Center, Seattle, Wash 98104-2499, USA. rhevner\@u.washington.edu}, Pages = {139-51}, Title = {Beyond laminar fate: toward a molecular classification of cortical projection/pyramidal neurons}, Uuid = {61CF7C23-C111-45ED-873D-96D6C16C3BE5}, Volume = {25}, Year = {2003}, url = {papers/Hevner_DevNeurosci2003.pdf}} @article{Hevner:2006, Abstract = {Glutamatergic, pyramidal-projection neurons are produced in the embryonic cerebral cortex by a series of genetically programmed fate choices, implemented in large part by developmental transcription factors. Our work has focused on Pax6, Tbr2/Eomes, NeuroD, and Tbr1, which are expressed sequentially during the neurogenesis of pyramidal-projection neurons. Recently, we have found that the same transcription factors are expressed, in the same order, during glutamatergic neurogenesis in the adult dentate gyrus, and (with modifications) in the developing cerebellum. While the precise functional significance of this transcription factor expression sequence is unknown, its common appearance in embryonic and adult neurogenesis, and in different brain regions, suggests it is part of a conserved genetic program that specifies general properties of glutamatergic neurons in these regions. Subtypes of glutamatergic neurons (e.g., layer-specific fates in the cortex) are further determined by combinations of transcription factors, superimposed on general sequential programs. These new perspectives on neurogenesis add to the conceptual framework for strategies to engineer neural stem cells for the repair of specific brain circuits.}, Author = {Hevner, and Hodge, and Daza, and Englund,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8500749}, Organization = {Department of Pathology, University of Washington, Harborview Medical Center, Harborview Pathology, Box 359791, 325 Ninth Ave., Seattle, WA 98104, USA.}, Pii = {S0168-0102(06)00067-8}, Pubmed = {16621079}, Title = {Transcription factors in glutamatergic neurogenesis: Conserved programs in neocortex, cerebellum, and adult hippocampus}, Uuid = {DD951484-7E39-4F91-BEB9-3617AC4C5EE2}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neures.2006.03.004}} @article{Hickey:1988, Abstract = {A crucial question in the study of immunological reactions in the central nervous system (CNS) concerns the identity of the parenchymal cells that function as the antigen-presenting cells in that organ. Rat bone marrow chimeras and encephalitogenic, major histocompatability--restricted T-helper lymphocytes were used to show that a subset of endogenous CNS cells, commonly termed "perivascular microglial cells," is bone marrow-derived. In addition, these perivascular cells are fully competent to present antigen to lymphocytes in an appropriately restricted manner. These findings are important for bone marrow transplantation and for neuroimmunological diseases such as multiple sclerosis.}, Author = {Hickey, W. F. and Kimura, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {T-Lymphocytes;Endothelium;Rats, Inbred Lew;Multiple Sclerosis;Astrocytes;Antigen-Presenting Cells;Animals;Chimera;Rats;Bone Marrow Transplantation;Histocompatibility Antigens;Bone Marrow;Research Support, U.S. Gov't, P.H.S.;Encephalomyelitis, Autoimmune, Experimental;Neuroglia;Graft vs Host Disease;Immunohistochemistry;Central Nervous System;Research Support, Non-U.S. Gov't}, Medline = {88099511}, Month = {1}, Nlm_Id = {0404511}, Number = {4837}, Organization = {Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104-6079.}, Pages = {290-2}, Pubmed = {3276004}, Title = {Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo}, Uuid = {8481DC25-D3B7-11D9-A0E9-000D9346EC2A}, Volume = {239}, Year = {1988}} @article{Hicks:1968, Abstract = {0003-276x Journal Article}, Author = {Hicks, S. P. and D'Amato, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Anat Rec}, Keywords = {DNA/biosynthesis;Cell Differentiation;Cerebral Cortex/*cytology/embryology/growth &development;Female;Rats;Autoradiography;Thymidine/metabolism;Neurons/*growth &development;A,F abstr;Pregnancy;Pregnancy, Animal;Animals, Newborn;Animals;Tritium;Cell Movement/physiology}, Number = {3}, Pages = {619-34}, Pubmed = {5664077}, Title = {Cell migrations to the isocortex in the rat}, Uuid = {2A0FC9B2-CDF0-11D9-B244-000D9346EC2A}, Volume = {160}, Year = {1968}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5664077}} @article{Hienola:2006, Abstract = {N-syndecan (syndecan-3) is a transmembrane proteoglycan that is abundantly expressed in the major axonal pathways and in the migratory routes of the developing brain. When ligated by heparin-binding (HB) growth-associated molecule (GAM; pleiotrophin), N-syndecan mediates cortactin-Src kinase-dependent neurite outgrowth. However, the functional role of N-syndecan in brain development remains unexplored. In this study, we show that N-syndecan deficiency perturbs the laminar structure of the cerebral cortex as a result of impaired radial migration. In addition, neural migration in the rostral migratory stream is impaired in the N-syndecan-null mice. We suggest that the migration defect depends on impaired HB-GAM-induced Src kinase activation and haptotactic migration. Furthermore, we show that N-syndecan interacts with EGF receptor (EGFR) at the plasma membrane and is required in EGFR-induced neuronal migration.}, Author = {Hienola, Anni and Tumova, Sarka and Kulesskiy, Evgeny and Rauvala, Heikki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0375356}, Number = {4}, Organization = {Neuroscience Center, University of Helsinki, 00014 Helsinki, Finland.}, Pages = {569-80}, Pii = {jcb.200602043}, Pubmed = {16908672}, Title = {N-syndecan deficiency impairs neural migration in brain}, Uuid = {66F56733-9450-4F78-87DD-2877E231DA03}, Volume = {174}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200602043}} @article{Hienola:2004, Abstract = {Proliferation of neural stem cells in the embryonic cerebral cortex is regulated by many growth factors and their receptors. Among the key molecules stimulating stem cell proliferation are FGF-2 and the FGF receptor-1. This ligand-receptor system is highly dependent on the surrounding heparan sulfates. We have found that heparin-binding growth-associated molecule (HB-GAM, also designated as pleiotrophin) regulates neural stem cell proliferation in vivo and in vitro. Deficiency of HB-GAM results in a pronounced, up to 50\%increase in neuronal density in the adult mouse cerebral cortex. This phenotype arises during cortical neurogenesis, when HB-GAM knockout embryos display an enhanced proliferation rate as compared to wild-type embryos. Further, our in vitro studies show that exogenously added HB-GAM inhibits formation and growth of FGF-2, but not EGF, stimulated neurospheres, restricts the number of nestin-positive neural stem cells, and inhibits FGF receptor phosphorylation. We propose that HB-GAM functions as an endogenous inhibitor of FGF-2 in stem cell proliferation in the developing cortex. 1044-7431 Journal Article}, Author = {Hienola, A. and Pekkanen, M. and Raulo, E. and Vanttola, P. and Rauvala, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {1}, Organization = {Neuroscience Center, Department of Biosciences and Institute of Biotechnology, University of Helsinki, Helsinki 00014, Finland.}, Pages = {75-88}, Pubmed = {15121180}, Title = {HB-GAM inhibits proliferation and enhances differentiation of neural stem cells}, Uuid = {659798A1-FE87-460A-A228-1849EEE58C3A}, Volume = {26}, Year = {2004}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15121180}} @article{Hilgetag:2006, Abstract = {The convoluted cortex of primates is instantly recognizable in its principal morphologic features, yet puzzling in its complex finer structure. Various hypotheses have been proposed about the mechanisms of its formation. Based on the analysis of databases of quantitative architectonic and connection data for primate prefrontal cortices, we offer support for the hypothesis that tension exerted by corticocortical connections is a significant factor in shaping the cerebral cortical landscape. Moreover, forces generated by cortical folding influence laminar morphology, and appear to have a previously unsuspected impact on cellular migration during cortical development. The evidence for a significant role of mechanical factors in cortical morphology opens the possibility of constructing computational models of cortical develoment based on physical principles. Such models are particularly relevant for understanding the relationship of cortical morphology to the connectivity of normal brains, and structurally altered brains in diseases of developmental origin, such as schizophrenia and autism.}, Author = {Hilgetag, and Barbas,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1553-7358}, Journal = {PLoS Comput Biol}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {101238922}, Number = {3}, Organization = {School of Engineering and Science, International University Bremen, Bremen, Germany.}, Pages = {e22}, Pubmed = {16557292}, Title = {Role of Mechanical Factors in the Morphology of the Primate Cerebral Cortex}, Uuid = {D582DE1E-7A77-4B86-ABA7-506F579A9CF8}, Volume = {2}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.0020022}} @article{Hill:2004, Abstract = {The chemokine stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptor CXCR4 have been implicated in homing of stem cells to the bone marrow and the homing of bone marrow-derived cells to sites of injury. Bone marrow cells infiltrate brain and give rise to long-term resident cells following injury. Therefore, SDF-1 and CXCR4 expression patterns in 40 mice were examined relative to the homing of bone marrow-derived cells to sites of ischemic injury using a stroke model. Mice received bone marrow transplants from green fluorescent protein (GFP) transgenic donors and later underwent a temporary middle cerebral artery suture occlusion (MCAo). SDF-1 was associated with blood vessels and cellular profiles by 24 hours through at least 30 days post-MCAo. SDF-1 expression was principally localized to the ischemic penumbra. The majority of SDF-1 expression was associated with reactive astrocytes; much of this was perivascular. GFP+ cells were associated with SDF-1-positive vessels and were also found in the neuropil of regions with increased SDF-1 immunoreactivity. Most vessel-associated GFP+ cells resemble pericytes or perivascular microglia and the majority of the GFP+ cells in the parenchyma displayed characteristics of activated microglial cells. These findings suggest SDF-1 is important in the homing of bone marrow-derived cells, especially monocytes, to areas of ischemic injury.}, Author = {Hill, William D. and Hess, David C. and Martin-Studdard, Angeline and Carothers, Jo J. and Zheng, Jianqing and Hale, David and Maeda, Manabu and Fagan, Susan C. and Carroll, James E. and Conway, Simon J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Receptors, CXCR4;Animals;Astrocytes;Up-Regulation;Infarction, Middle Cerebral Artery;Bone Marrow Transplantation;Microscopy, Confocal;Research Support, U.S. Gov't, Non-P.H.S.;Microglia;Female;Brain;Mice, Transgenic;Cell Movement;Cerebrovascular Circulation;Green Fluorescent Proteins;Disease Models, Animal;Male;11 Glia;In Situ Hybridization;Research Support, U.S. Gov't, P.H.S.;Brain Ischemia;Chemokines, CXC;Mice;Immunohistochemistry;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {23109187}, Month = {1}, Nlm_Id = {2985192R}, Number = {1}, Organization = {Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912-2000, USA. whill\@mail.mcg.edu}, Pages = {84-96}, Pubmed = {14748564}, Title = {SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury}, Uuid = {48A02ED9-1852-4C21-832F-BD0326CA3CA0}, Volume = {63}, Year = {2004}} @article{Hill:2005, Abstract = {When the brain goes from wakefulness to sleep, cortical neurons begin to undergo slow oscillations in their membrane potential that are synchronized by thalamocortical circuits and reflected in EEG slow waves. To provide a self-consistent account of the transition from wakefulness to sleep and of the generation of sleep slow waves, we have constructed a large-scale computer model that encompasses portions of two visual areas and associated thalamic and reticular thalamic nuclei. Thousands of model neurons, incorporating several intrinsic currents, are interconnected with millions of thalamocortical, corticothalamic, and both intra- and interareal corticocortical connections. In the waking mode, the model exhibits irregular spontaneous firing and selective responses to visual stimuli. In the sleep mode, neuromodulatory changes lead to slow oscillations that closely resemble those observed in vivo and in vitro. A systematic exploration of the effects of intrinsic currents and network parameters on the initiation, maintenance, and termination of slow oscillations shows the following. 1) An increase in potassium leak conductances is sufficient to trigger the transition from wakefulness to sleep. 2) The activation of persistent sodium currents is sufficient to initiate the up-state of the slow oscillation. 3) A combination of intrinsic and synaptic currents is sufficient to maintain the up-state. 4) Depolarization-activated potassium currents and synaptic depression terminate the up-state. 5) Corticocortical connections synchronize the slow oscillation. The model is the first to integrate intrinsic neuronal properties with detailed thalamocortical anatomy and reproduce neural activity patterns in both wakefulness and sleep, thereby providing a powerful tool to investigate the role of sleep in information transmission and plasticity.}, Author = {Hill, Sean and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Wakefulness;Synapses;Evoked Potentials;comparative study;Humans;Afferent Pathways;Feedback;Synaptic Transmission;Models, Biological;Reaction Time;research support, non-u.s. gov't;Time Factors;Sleep;Computer Simulation;Potassium;Thalamus;Cerebral Cortex;21 Neurophysiology;24 Pubmed search results 2008;Neural Inhibition;Electroencephalography;Models, Neurological}, Month = {3}, Nlm_Id = {0375404}, Number = {3}, Organization = {Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Boulevard, Madison, WI 53719-1176, USA. seanhill\@wisc.edu}, Pages = {1671-98}, Pii = {00915.2004}, Pubmed = {15537811}, Title = {Modeling sleep and wakefulness in the thalamocortical system}, Uuid = {D522FFD0-CDF2-41A3-8DD5-4DEA4DF92B7C}, Volume = {93}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00915.2004}} @article{Hill:2005a, Abstract = {Rapidly advancing knowledge of genome structure and sequence enables new means for the analysis of specific DNA changes associated with the differences between the human brain and that of other mammals. Recent studies implicate evolutionary changes in messenger RNA and protein expression levels, as well as DNA changes that alter amino acid sequences. We can anticipate having a systematic catalogue of DNA changes in the lineage leading to humans, but an ongoing challenge will be relating these changes to the anatomical and functional differences between our brain and that of our ancient and more recent ancestors.}, Author = {Hill, Robert Sean and Walsh, Christopher A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {10 Development;Research Support, Non-U.S. Gov't;Comparative Study;Phylogeny;Evolution, Molecular;Research Support, U.S. Gov't, P.H.S.;Gene Expression Regulation;Research Support, N.I.H., Extramural;Organ Size;Evolution;Animals;Humans;Cerebral Cortex;Brain;19 Neocortical evolution}, Month = {9}, Nlm_Id = {0410462}, Number = {7055}, Organization = {Division of Neurogenetics and Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, and Department of Neurology, Harvard Medical School, Room 266, New Research Building, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.}, Pages = {64-7}, Pii = {nature04103}, Pubmed = {16136130}, Title = {Molecular insights into human brain evolution}, Uuid = {AAC914E8-31A2-411A-8655-39CC592B5B35}, Volume = {437}, Year = {2005}, url = {papers/Hill_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04103}} @article{Himanen:2007, Abstract = {Eph receptors are the largest subfamily of receptor tyrosine kinases regulating cell shape, movements, and attachment. The interactions of the Ephs with their ephrin ligands are restricted to the sites of cell-cell contact since both molecules are membrane attached. This review summarizes recent advances in our understanding of the molecular mechanisms underlining the diverse functions of the molecules during development and in the adult organism. The unique properties of this signaling system that are of highest interest and have been the focus of intense investigations are as follows: (i) the signal is simultaneously transduced in both ligand-expressing cells and receptor-expressing cells, (ii) signaling via the same molecules can generate opposing cellular reactions depending on the context, and (iii) the Ephs and the ephrins are divided into two subclasses with promiscuous intrasubclass interactions, but rarely observed intersubclass interactions.}, Author = {Himanen, Juha-Pekka P. and Saha, Nayanendu and Nikolov, Dimitar B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0955-0674}, Journal = {Curr Opin Cell Biol}, Keywords = {10 Development;Signal Transduction;Enzyme Activation;Humans;Ephrins;Enzyme Inhibitors;Nervous System;review;Cell Communication;research support, non-u.s. gov't;10 circuit formation;Cell Adhesion;Protein Structure, Tertiary;Endocytosis;research support, n.i.h., extramural;24 Pubmed search results 2008;Receptor, EphA1;Peptides}, Month = {10}, Nlm_Id = {8913428}, Number = {5}, Organization = {Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.}, Pages = {534-42}, Pii = {S0955-0674(07)00121-4}, Pubmed = {17928214}, Title = {Cell-cell signaling via Eph receptors and ephrins}, Uuid = {1AA9C550-4C59-408B-B3E5-9C14A638CCC7}, Volume = {19}, Year = {2007}, url = {papers/Himanen_CurrOpinCellBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ceb.2007.08.004}} @article{Himanen:2003, Abstract = {Eph receptors, the largest subfamily of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape and mobility. Both Ephs and ephrins are membrane-bound and their interactions at sites of cell-cell contact initiate unique bidirectional signaling cascades, with information transduced in both the receptor-expressing and the ligand-expressing cells. Recent structural and biophysical studies summarized in this review reveal unique molecular features not previously observed in any other receptor-ligand families and explain many of the biochemical and signaling properties of Ephs and ephrins. Of particular importance is the insight into how approximation of ligand-expressing and receptor-expressing cells could lead to the formation and activation of highly ordered signaling centers at cell-cell interfaces.}, Author = {Himanen, Juha-Pekka P. and Nikolov, Dimitar B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Receptors, Eph Family;10 Development;research support, non-u.s. gov't;Ligands;Protein Conformation;Cell Communication;Signal Transduction;10 circuit formation;comparative study;Ephrins;research support, u.s. gov't, p.h.s.;Animals;Cells, Cultured;24 Pubmed search results 2008;review;Receptor Protein-Tyrosine Kinases}, Month = {1}, Nlm_Id = {7808616}, Number = {1}, Organization = {Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.}, Pages = {46-51}, Pii = {S016622360200005X}, Pubmed = {12495863}, Title = {Eph signaling: a structural view}, Uuid = {5DC897E6-F938-4A45-8FBF-3F800AB03325}, Volume = {26}, Year = {2003}} @article{Himes:2006, Abstract = {We report in this study that activation of the JNK by the growth factor, CSF-1 is critical for macrophage development, proliferation, and survival. Inhibition of JNK with two distinct classes of inhibitors, the pharmacological agent SP600125, or the peptide D-JNKI1 resulted in cell cycle inhibition with an arrest at the G(2)/M transition and subsequent apoptosis. JNK inhibition resulted in decreased expression of CSF-1R (c-fms) and Bcl-x(L) mRNA in mature macrophages and repressed CSF-1-dependent differentiation of bone marrow cells to macrophages. Macrophage sensitivity to JNK inhibitors may be linked to phosphorylation of the PU.1 transcription factor. Inhibition of JNK disrupted PU.1 binding to an element in the c-fms gene promoter and decreased promoter activity. Promoter activity could be restored by overexpression of PU.1. A comparison of expression profiles of macrophages with 22 other tissue types showed that genes that signal JNK activation downstream of tyrosine kinase receptors, such as focal adhesion kinase, Nck-interacting kinase, and Rac1 and scaffold proteins are highly expressed in macrophages relative to other tissues. This pattern of expression may underlie the novel role of JNK in macrophages.}, Author = {Himes, S. Roy and Sester, David P. and Ravasi, Timothy and Cronau, Stephen L. and Sasmono, Tedjo and Hume, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {11 Glia}, Month = {2}, Nlm_Id = {2985117R}, Number = {4}, Organization = {Cooperative Research Centre for Chronic Inflammatory Disease, Institute for Molecular Biosciences, University of Queensland, Brisbane, Australia.}, Pages = {2219-28}, Pii = {176/4/2219}, Pubmed = {16455978}, Title = {The JNK Are Important for Development and Survival of Macrophages}, Uuid = {CF8CF5CA-FD34-45E0-8DFC-5B82BE2F2EF9}, Volume = {176}, Year = {2006}} @article{Hinds:1968, Abstract = {0021-9967 Journal Article}, Author = {Hinds, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Thymidine;01 Adult neurogenesis general;Cell Differentiation;Neuroglia;Limbic System/*cytology/*growth &development;*Neuroglia;Limbic System;Autoradiography;*Cell Differentiation;Animals, Newborn;Tritium;A, B abstr;Animals;Mice}, Medline = {69169667}, Month = {11}, Nlm_Id = {0406041}, Number = {3}, Pages = {305-22}, Pubmed = {5721257}, Title = {Autoradiographic study of histogenesis in the mouse olfactory bulb. II. Cell proliferation and migration}, Uuid = {DCAED3E1-D322-11DA-941C-000D9346EC2A}, Volume = {134}, Year = {1968}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901340305}, Bdsk-Url-2 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5721257}} @article{Hinds:1968a, Abstract = {0021-9967 Journal Article}, Author = {Hinds, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Comp Neurol}, Keywords = {Thymidine;01 Adult neurogenesis general;Limbic System/*cytology/*growth &development;*Neuroglia;*Neurons;Autoradiography;Cell Division;*Cell Differentiation;Animals, Newborn;Tritium;A, B abstr;Animals;Mice}, Number = {3}, Pages = {287-304}, Pubmed = {5721256}, Title = {Autoradiographic study of histogenesis in the mouse olfactory bulb. I. Time of origin of neurons and neuroglia}, Uuid = {C1229D21-8751-4D27-922C-549DA75BADBD}, Volume = {134}, Year = {1968}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=5721256}} @article{Hirase:2004, Abstract = {Large and long-lasting cytosolic calcium surges in astrocytes have been described in cultured cells and acute slice preparations. The mechanisms that give rise to these calcium events have been extensively studied in vitro. However, their existence and functions in the intact brain are unknown. We have topically applied Fluo-4 AM on the cerebral cortex of anesthetized rats, and imaged cytosolic calcium fluctuation in astrocyte populations of superficial cortical layers in vivo, using two-photon laser scanning microscopy. Spontaneous [Ca(2+)](i) events in individual astrocytes were similar to those observed in vitro. Coordination of [Ca(2+)](i) events among astrocytes was indicated by the broad cross-correlograms. Increased neuronal discharge was associated with increased astrocytic [Ca(2+)](i) activity in individual cells and a robust coordination of [Ca(2+)](i) signals in neighboring astrocytes. These findings indicate potential neuron-glia communication in the intact brain.}, Author = {Hirase, Hajime and Qian, Lifen and Barth{\'o}, Peter and Buzs{\'a}ki, Gy{\"o}rgy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {Research Support, N.I.H., Extramural;24 Pubmed search results 2008;21 Calcium imaging;Immunohistochemistry;Xanthenes;Male;Cerebral Cortex;Animals;Cells, Cultured;Electrophysiology;Brain;Cytosol;Research Support, U.S. Gov't, P.H.S.;Signal Transduction;Calcium Signaling;Cell Communication;Aniline Compounds;Rats, Sprague-Dawley;Neuroglia;Calcium;Rats;Female;Microscopy, Video;Microscopy, Confocal;21 Neurophysiology;Models, Biological;Neurons;Research Support, Non-U.S. Gov't;Astrocytes;Fluorescent Dyes}, Month = {4}, Nlm_Id = {101183755}, Number = {4}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey, USA. hirase\@axon.rutgers.edu}, Pages = {E96}, Pubmed = {15094801}, Title = {Calcium dynamics of cortical astrocytic networks in vivo}, Uuid = {D1F218D3-C597-4CC9-AEB6-82606B20E0F9}, Volume = {2}, Year = {2004}, url = {papers/Hirase_PLoSBiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0020096}} @article{Hirotsune:1998, Abstract = {Heterozygous mutation or deletion of the beta subunit of platelet-activating factor acetylhydrolase (PAFAH1B1, also known as LIS1) in humans is associated with type I lissencephaly, a severe developmental brain disorder thought to result from abnormal neuronal migration. To further understand the function of PAFAH1B1, we produced three different mutant alleles in mouse Pafah1b1. Homozygous null mice die early in embryogenesis soon after implantation. Mice with one inactive allele display cortical, hippocampal and olfactory bulb disorganization resulting from delayed neuronal migration by a cell-autonomous neuronal pathway. Mice with further reduction of Pafah1b1 activity display more severe brain disorganization as well as cerebellar defects. Our results demonstrate an essential, dosage-sensitive neuronal-specific role for Pafah1b1 in neuronal migration throughout the brain, and an essential role in early embryonic development. The phenotypes observed are distinct from those of other mouse mutants with neuronal migration defects, suggesting that Pafah1b1 participates in a novel pathway for neuronal migration.}, Author = {Hirotsune, S. and Fleck, M. W. and Gambello, M. J. and Bix, G. J. and Chen, A. and Clark, G. D. and Ledbetter, D. H. and McBain, C. J. and Wynshaw-Boris, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {10 Development;Microtubule-Associated Proteins;Animals;Cells, Cultured;Proteins;1-Alkyl-2-acetylglycerophosphocholine Esterase;Cell Movement;Hippocampus;research support, non-u.s. gov't;Embryonic and Fetal Development;Olfactory Bulb;Abnormalities, Multiple;Cerebral Cortex;Neurons;Mice, Knockout;10 genetics malformation;Genotype;Cerebellum;research support, u.s. gov't, p.h.s.;Mice;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {9216904}, Number = {4}, Organization = {Genetic Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.}, Pages = {333-9}, Pubmed = {9697693}, Title = {Graded reduction of Pafah1b1 (Lis1) activity results in neuronal migration defects and early embryonic lethality}, Uuid = {C0F16862-BA39-4EE5-BDEB-CFBDA85B809B}, Volume = {19}, Year = {1998}, url = {papers/Hirotsune_NatGenet1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/1221}} @article{Hisatomi:2003, Abstract = {The effective phagocytotic clearance of apoptotic debris is fundamental to the maintenance of neural tissues during apoptosis. Retinal photoreceptors undergo apoptosis after retinal detachment. Although their induction phase of apoptosis has been well discussed, their phagocytotic process remains quite unclear. We herein demonstrate that apoptotic photoreceptors are selectively eliminated from their physiological localization, the outer nuclear layer, to the subretinal space, and then phagocytosed by monocyte-derived macrophages. This could be shown by an ultrastructural and immunophenotypic analysis. Moreover, in chimera mice expressing transgenic green fluorescent protein in bone marrow-derived cells, the local infiltration of macrophages could be detected after retinal detachment-induced photoreceptor apoptosis. The local injection of an antibody blocking the phosphatidylserine receptor (PSR) or a peptide (GRGDSP)-blocking integrin alphavbeta3 revealed that phagocytotic clearance involves the PSR as well as integrin alphavbeta3 in vivo. Importantly, the level of blockade obtained with these reagents was different. Although anti-PSR increased the frequency of apoptotic cells that fail to bind to macrophages, GRGDSP prevented the engulfment (but not the recognition) of apoptotic photoreceptor cells by macrophages. To our knowledge, this is the first report describing the mechanisms through which apoptotic photoreceptors are selectively eliminated via a directional process in the subretinal space.}, Author = {Hisatomi, Toshio and Sakamoto, Taiji and Sonoda, Koh-Hei H. and Tsutsumi, Chikako and Qiao, Hong and Enaida, Hiroshi and Yamanaka, Ichiro and Kubota, Toshiaki and Ishibashi, Tatsuro and Kura, Shinobu and Susin, Santos A. and Kroemer, Guido}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Retina;Microscopy, Electron, Scanning;Phagocytosis;Animals;Rats, Inbred BN;Macrophages;Rats;Oligopeptides;Receptors, Cell Surface;Apoptosis;Retinal Degeneration;Mice, Transgenic;11 Glia;Immunophenotyping;Green Fluorescent Proteins;Microscopy, Fluorescence;Antibodies;Integrin alphaVbeta3;In Situ Nick-End Labeling;Photoreceptors;Mice;Luminescent Proteins;Membrane Proteins;Microscopy, Electron;Immunohistochemistry;Flavoproteins;Research Support, Non-U.S. Gov't}, Medline = {22642309}, Month = {6}, Nlm_Id = {0370502}, Number = {6}, Organization = {Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. hisatomi\@med.kyushu-u.ac.jp}, Pages = {1869-79}, Pubmed = {12759244}, Title = {Clearance of apoptotic photoreceptors: elimination of apoptotic debris into the subretinal space and macrophage-mediated phagocytosis via phosphatidylserine receptor and integrin alphavbeta3}, Uuid = {44A415D7-F573-40D2-871B-3F8516DEF038}, Volume = {162}, Year = {2003}} @article{Hochedlinger:2005, Abstract = {The POU-domain transcription factor Oct-4 is normally expressed in pluripotent cells of the mammalian embryo. In addition, germ-cell tumors and a few somatic tumors show detectable expression of Oct-4. While Oct-4's role during preimplantation development is to maintain embryonic cells in a pluripotent state, little is known about its potential oncogenic properties. Here we investigate the effect of ectopic Oct-4 expression on somatic tissues of adult mice using a doxycycline-dependent expression system. Activation of Oct-4 results in dysplastic growths in epithelial tissues that are dependent on continuous Oct-4 expression. Dysplastic lesions show an expansion of progenitor cells and increased beta-catenin transcriptional activity. In the intestine, Oct-4 expression causes dysplasia by inhibiting cellular differentiation in a manner similar to that in embryonic cells. These data show that certain adult progenitors remain competent to interpret key embryonic signals and support the notion that progenitor cells are a driving force in tumorigenesis.}, Author = {Hochedlinger, Konrad and Yamada, Yasuhiro and Beard, Caroline and Jaenisch, Rudolf}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0413066}, Number = {3}, Organization = {Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA.}, Pages = {465-77}, Pii = {S0092-8674(05)00163-7}, Pubmed = {15882627}, Title = {Ectopic expression of Oct-4 blocks progenitor-cell differentiation and causes dysplasia in epithelial tissues}, Uuid = {9B6FD7A1-2DC4-493D-ACDA-6A8F7F18B155}, Volume = {121}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.02.018}} @article{Hoek:2000, Abstract = {OX2 (CD200) is a broadly expressed membrane glycoprotein, shown here to be important for regulation of the macrophage lineage. In mice lacking CD200, macrophage lineage cells, including brain microglia, exhibited an activated phenotype and were more numerous. Upon facial nerve transection, damaged CD200-deficient neurons elicited an accelerated microglial response. Lack of CD200 resulted in a more rapid onset of experimental autoimmune encephalomyelitis (EAE). Outside the brain, disruption of CD200-CD200 receptor interaction precipitated susceptibility to collagen-induced arthritis (CIA) in mice normally resistant to this disease. Thus, in diverse tissues OX2 delivers an inhibitory signal for the macrophage lineage.}, Author = {Hoek, R. M. and Ruuls, S. R. and Murphy, C. A. and Wright, G. J. and Goddard, R. and Zurawski, S. M. and Blom, B. and Homola, M. E. and Streit, W. J. and Brown, M. H. and Barclay, A. N. and Sedgwick, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Animals;Gene Targeting;Encephalomyelitis, Experimental Autoimmune;Macrophages;Rats;Microglia;Denervation;Antigens, Surface;Lymph Nodes;Macrophage Activation;Not relevant;11 Glia;Mice, Inbred C57BL;Joints;Arthritis, Experimental;Support, Non-U.S. Gov't;Receptors, Immunologic;Cell Lineage;Neurons;Down-Regulation;Mice;Central Nervous System;Facial Nerve;Spleen}, Medline = {20553647}, Month = {12}, Nlm_Id = {0404511}, Number = {5497}, Organization = {DNAX Research Institute of Molecular and Cellular Biology, 901 California Avenue, Palo Alto, CA 94304, USA.}, Pages = {1768-71}, Pii = {9024}, Pubmed = {11099416}, Title = {Down-regulation of the macrophage lineage through interaction with OX2 (CD200)}, Uuid = {96B560F1-4424-49F4-BBE0-C0533FCBD187}, Volume = {290}, Year = {2000}} @article{Hof:1999, Abstract = {The three calcium-binding proteins parvalbumin, calbindin, and calretinin are found in morphologically distinct classes of inhibitory interneurons as well as in some pyramidal neurons in the mammalian neocortex. Although there is a wide variability in the qualitative and quantitative characteristics of the neocortical subpopulations of calcium-binding protein-immunoreactive neurons in mammals, most of the available data show that there is a fundamental similarity among the mammalian species investigated so far, in terms of the distribution of parvalbumin, calbindin, and calretinin across the depth of the neocortex. Thus, calbindin- and calretinin-immunoreactive neurons are predominant in layers II and III, but are present across all cortical layers, whereas parvalbumin-immunoreactive neurons are more prevalent in the middle and lower cortical layers. These different neuronal populations have well defined regional and laminar distribution, neurochemical characteristics and synaptic connections, and each of these cell types displays a particular developmental sequence. Most of the available data on the development, distribution and morphological characteristics of these calcium-binding proteins are from studies in common laboratory animals such as the rat, mouse, cat, macaque monkey, as well as from postmortem analyses in humans, but there are virtually no data on other species aside of a few incidental reports. In the context of the evolution of mammalian neocortex, the distribution and morphological characteristics of calcium-binding protein-immunoreactive neurons may help defining taxon-specific patterns that may be used as reliable phylogenetic traits. It would be interesting to extend such neurochemical analyses of neuronal subpopulations to other species to assess the degree to which neurochemical specialization of particular neuronal subtypes, as well as their regional and laminar distribution in the cerebral cortex, may represent sets of derived features in any given mammalian order. This could be particularly interesting in view of the consistent differences in neurochemical typology observed in considerably divergent orders such as cetaceans and certain families of insectivores and metatherians, as well as in monotremes. The present article provides an overview of calcium-binding protein distribution across a large number of representative mammalian species and a review of their developmental patterns in the species where data are available. This analysis demonstrates that while it is likely that the developmental patterns are quite consistent across species, at least based on the limited number of species for which ontogenetic data exist, the distribution and morphology of calcium-binding protein- containingneurons varies substantially among mammalian orders and that certain species show highly divergent patterns compared to closely related taxa. Interestingly, primates, carnivores, rodents and tree shrews appear closely related on the basis of the observed patterns, marsupials show some affinities with that group, whereas prototherians have unique patterns. Our findings also support the relationships of cetaceans and ungulates, and demonstrates possible affinities between carnivores and ungulates, as well as the existence of common, probably primitive, traits in cetaceans and insectivores.}, Author = {Hof, P. R. and Glezer and Conde, F. and Flagg, R. A. and Rubin, M. B. and Nimchinsky, E. A. and Vogt Weisenhorn, D. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Chem Neuroanat}, Keywords = {Human;Mammals/*physiology;Comparative Study;Phylogeny;Animal;Parvalbumins/*physiology;12 Interneuron development;Neurons/physiology;Calcium-Binding Protein, Vitamin D-Dependent/*physiology;H;Neocortex/growth &development/*physiology}, Number = {2}, Organization = {Fishberg Research Center for Neurobiology, Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, NY 10029, USA. patrick\_hof\@fishmailserver.neuro.mssm.edu}, Pages = {77-116.}, Title = {Cellular distribution of the calcium-binding proteins parvalbumin, calbindin, and calretinin in the neocortex of mammals: phylogenetic and developmental patterns}, Uuid = {EB261684-E4D2-46A3-B2FE-96ED29D7BA59}, Volume = {16}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10223310}} @article{Hoffman:1992, Abstract = {The pathogenesis of progressive spastic paraparesis [HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP)], a serious consequence of human T-cell leukemia virus type I (HTLV-I) infection, is unclear. T and B lymphocytes can be naturally infected by HTLV-I, but the susceptibility to HTLV-I infection of other cell types that could contribute to the pathogenesis of HAM/TSP has not been determined. We found that a human monocyte cell line (THP-1), primary human peripheral blood monocytes, and isolated microglial cells but not astrocytes or oligodendroglial cells derived from adult human brain were infected by HTLV-I in vitro. Infection with HTLV-I enhanced the secretion of interleukin 6 in human microglial cell-enriched cultures but did not stimulate the release of interleukin 1 from monocytes or microglial cells. Tumor necrosis factor alpha production was stimulated by HTLV-I infection of monocytes and microglial cells and could be enhanced by suboptimal amounts of lipopolysaccharide. Since both tumor necrosis factor alpha and interleukin 6 have been implicated in inflammatory demyelination and gliosis, our findings suggest that human microglial cells and monocytes infected with and activated by HTLV-I could play a role in the pathogenesis of HAM/TSP.}, Author = {Hoffman, P. M. and Dhib-Jalbut, S. and Mikovits, J. A. and Robbins, D. S. and Wolf, A. L. and Bergey, G. K. and Lohrey, N. C. and Weislow, O. S. and Ruscetti, F. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Monocytes;Tumor Necrosis Factor;Neuroglia;Tumor Cells, Cultured;Human;Human T-lymphotropic virus 1;Not relevant;In Vitro;11 Glia;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;RNA, Viral;Interleukin-6;RNA, Messenger;Brain;Cells, Cultured;HTLV-I Infections}, Medline = {93101611}, Month = {12}, Nlm_Id = {7505876}, Number = {24}, Organization = {Retrovirus Research Center, Department of Veterans Affairs Medical Center, Baltimore, MD 21218.}, Pages = {11784-8}, Pubmed = {1465399}, Title = {Human T-cell leukemia virus type I infection of monocytes and microglial cells in primary human cultures}, Uuid = {D3E22DB7-9BFE-4429-9A56-B6886196E678}, Volume = {89}, Year = {1992}, url = {papers/Hoffman_ProcNatlAcadSciUSA1992.pdf}} @article{Holden:1977, Abstract = {Utilizing controlled cryopreservation techniques, we were able to standardize the 51Cr release cytotoxicity assay and thereby ensured reliable comparisons between results obtained on different days. Optimal conditions for freezing of both effector and target cells were quite similar. Dimethyl sulfoxide (DMSO) at a concentration of 7.5-10.0\%was employed as the cryoprotective agent and cells were frozen at the rate of -1 degrees C/minute. The handling procedures for the cells before and after freezing were important. Factors affecting recovery of functional reactivity were related to toxicity of DMSO for the cells, the osmotic stress placed upon the cells as the DMSO was being removed after thawing, the handling temperature of the freshly thawed cells, and the susceptibility of cells to mechanical damage immediately after thawing. The recovery of lymphocytes after freezing was about 70\%; the recovery of cytotoxicity was around 85\%. Syngeneic cytotoxic reactivity induced by inoculation with the Moloney strain of murine sarcoma virus was cryopreserved, as were allogeneic cytotoxicity and natural cytotoxic reactivity. Multiple tests employing effector cells from the same frozen pool gave reproducible results; the standard error of the mean percent cytotoxicity was less than 1.5\%. Cryopreserved target cells gave decreased day-to-day variability in susceptibility to lysis, since the same population of cells could be employed in each assay. These results demonstrated conclusively that we can now have a constant source of effector cells and target cells, which can be used from assay to assay as an internal standard. 0027-8874 Journal Article}, Author = {Holden, H. T. and Oldham, R. K. and Ortaldo, J. R. and Herberman, R. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Natl Cancer Inst}, Keywords = {Antigens, Viral;Animals;Cell Survival/drug effects;Chromium Radioisotopes;Cells, Cultured;Moloney murine leukemia virus/immunology;Comparative Study;Sarcoma, Experimental/immunology;Antigens, Neoplasm;EE, DMSO, abstr;08 Aberrant cell cycle;Antilymphocyte Serum;Male;Time Factors;Dimethyl Sulfoxide/pharmacology;Mice, Inbred Strains;Temperature;Cryoprotective Agents;Lymphocytes/immunology;Freezing;Cytotoxicity Tests, Immunologic/*methods;Support, U.S. Gov't, P.H.S.;Immunity, Cellular;Mice;Neoplasms, Experimental/immunology;Culture Media}, Number = {3}, Pages = {611-22}, Pubmed = {839557}, Title = {Standardization of the chromium-51 release, cell-mediated cytotoxicity assay: cryopreservation of mouse effector and target cells}, Uuid = {F31C61FA-F566-4680-8832-3586A9DB5D08}, Volume = {58}, Year = {1977}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=839557}} @article{Holevinsky:1995, Abstract = {Stimulation of macrophages induces the "respiratory burst" response which is associated with the generation of superoxide (O2-), a drop in cytoplasmic pH, and a pronounced depolarization of the membrane potential. The purpose of the present studies was to determine whether an increase in O2- was temporally related to changes in membrane potential and transmembrane current. Release of O2- at the single cell level was photometrically monitored during phagocytosis of immune complexes while simultaneously measuring whole-cell current. Membrane depolarization and the generation of a non-selective current followed an increase in O2- production with a variable lag time which was correlated with the state of cellular maturation in culture. In the absence of phagocytosis, the exposure of macrophages to O2- generated by a xanthine-xanthine oxidase reaction activated a non-selective current similar to that seen after phagocytosis. These results provide the first demonstration of the relationship between free radical release and the ensuing electrophysiological signaling events which are linked to particle engulfment in phagocytic cells.}, Author = {Holevinsky, K. O. and Nelson, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {24 Pubmed search results 2008;Receptors, Fc;Respiratory Burst;Research Support, U.S. Gov't, P.H.S.;11 Glia;Macrophages;Superoxides;Cells, Cultured;Humans;Membrane Potentials;Phagocytosis;Free Radicals}, Medline = {95229654}, Month = {4}, Nlm_Id = {2985121R}, Number = {14}, Organization = {Department of Neurology, University of Chicago, Illinois 60637, USA.}, Pages = {8328-36}, Pubmed = {7713941}, Title = {Simultaneous detection of free radical release and membrane current during phagocytosis}, Uuid = {4B8FA383-08EF-45F1-95E6-E4B088F526C0}, Volume = {270}, Year = {1995}} @article{Holland:1996, Abstract = {Receptor tyrosine kinases of the EPH class have been implicated in the control of axon guidance and fasciculation, in regulating cell migration, and in defining compartments in the developing embryo. Efficient activation of EPH receptors generally requires that their ligands be anchored to the cell surface, either through a transmembrane (TM) region or a glycosyl phosphatidylinositol (GPI) group. These observations have suggested that EPH receptors can transduce signals initiated by direct cell-cell interaction. Genetic analysis of Nuk, a murine EPH receptor that binds TM ligands, has raised the possibility that these ligands might themselves have a signalling function. Consistent with this, the three known TM ligands have a highly conserved cytoplasmic region, with multiple potential sites for tyrosine phosphorylation. Here we show that challenging cells that express the TM ligands Elk-L or Htk-L with the clustered ectodomain of Nuk induces phosphorylation of the ligands on tyrosine, a process that can be mimicked both in vitro and in vivo by an activated Src tyrosine kinase. Co-culture of cells expressing a TM ligand with cells expressing Nuk leads to tyrosine phosphorylation of both the ligand and Nuk. These results suggest that the TM ligands are associated with a tyrosine kinase, and are inducibly phosphorylated upon binding Nuk, in a fashion reminiscent of cytokine receptors. Furthermore, we show that TM ligands, as well as Nuk, are phosphorylated on tyrosine in mouse embryos, indicating that this is a physiological process. EPH receptors and their TM ligands therefore mediate bidirectional cell signalling. 0028-0836 Journal Article}, Author = {Holland, S. J. and Gale, N. W. and Mbamalu, G. and Yancopoulos, G. D. and Henkemeyer, M. and Pawson, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Nature}, Keywords = {10 Development;Recombinant Fusion Proteins/metabolism;Animals;Rats;Phosphorylation;*Signal Transduction;Proto-Oncogene Proteins/*metabolism;COS Cells;Ephrin-B2;Membrane Proteins/*metabolism;Receptor Protein-Tyrosine Kinases/*metabolism;Support, Non-U.S. Gov't;Cell Membrane/metabolism;Tyrosine/metabolism;Coculture;Tumor Cells, Cultured;Mice;Amino Acid Sequence;Molecular Sequence Data;F;Ligands}, Number = {6602}, Organization = {Programme in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.}, Pages = {722-5}, Pubmed = {8878483}, Title = {Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands}, Uuid = {80E87EA1-5599-4F2F-81FA-1A5B7A878196}, Volume = {383}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8878483}} @article{Holland:1974, Author = {Holland, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0036-8733}, Journal = {Sci Am}, Keywords = {15 ERVs retroelements;24 Pubmed search results 2008;Cricetinae;Virus Replication;15 Retrovirus mechanism;Animals;Slow Virus Diseases;RNA Viruses;Humans;Mice}, Medline = {74083540}, Month = {2}, Nlm_Id = {0404400}, Number = {2}, Pages = {32-40}, Pubmed = {4810514}, Title = {Slow, inapparent and recurrent viruses}, Uuid = {8DFFA399-4328-11DB-A5D2-000D9346EC2A}, Volume = {230}, Year = {1974}} @article{Holmberg:2002, Abstract = {The ephrins and their Eph receptors have emerged as repulsive cues for growing axons during the past decade. Since then, great effort has been made to understand the significance and mechanisms of Eph-mediated repulsion. More recently, it has become clear that ephrins perform in many more developmental processes than the repulsion-dependent establishment of topography in the nervous system. As numerous studies suggest functions more akin to adhesion or attraction than to repulsion, increasing attention is now being paid to the intracellular mechanisms that might explain this duality.}, Author = {Holmberg, Johan and Fris{\'e}n, Jonas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Fetal Proteins;Receptor Protein-Tyrosine Kinases;Transcription Factors;10 Development;research support, non-u.s. gov't;Cell Adhesion;Membrane Proteins;24 Pubmed search results 2008;Ephrin-A2;Signal Transduction;10 circuit formation;Ephrin-B2;Animals;Humans;Receptor, EphA4;review;Axons}, Month = {5}, Nlm_Id = {7808616}, Number = {5}, Organization = {Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.}, Pages = {239-43}, Pii = {S0166223602021495}, Pubmed = {11972959}, Title = {Ephrins are not only unattractive}, Uuid = {0ED889E1-E6C0-4AED-BA9A-F5B12208A532}, Volume = {25}, Year = {2002}} @article{Holmes:1999, Abstract = {In some children, epilepsy is a catastrophic condition, leading to significant intellectual and behavioral impairment, but little is known about the consequences of recurrent seizures during development. In the present study, we evaluated the effects of 15 daily pentylenetetrazol-induced convulsions in immature rats beginning at postnatal day (P) 1, 10, or 60. In addition, we subjected another group of P10 rats to twice daily seizures for 15 days. Both supragranular and terminal sprouting in the CA3 hippocampal subfield was assessed in Timm-stained sections by using a rating scale and density measurements. Prominent sprouting was seen in the CA3 stratum pyramidale layer in all rats having 15 daily seizures, regardless of the age when seizures began. Based on Timm staining in control P10, P20, and P30 rats, the terminal sprouting in CA3 appears to be new growth of axons and synapses as opposed to a failure of normal regression of synapses. In addition to CA3 terminal sprouting, rats having twice daily seizures had sprouting noted in the dentate supragranular layer, predominately in the inferior blade of the dentate, and had a decreased seizure threshold when compared with controls. Cell counting of dentate granule cells, CA3, CA1, and hilar neurons, with unbiased stereological methods demonstrated no differences from controls in rats with daily seizures beginning at P1 or P10, whereas adult rats with daily seizures had a significant decrease in CA1 neurons. Rats that received twice daily seizures on P10-P25 had an increase in dentate granule cells. This study demonstrates that, like the mature brain, immature animals have neuronal reorganization after recurrent seizures, with mossy fiber sprouting in both the CA3 subfield and supragranular region. In the immature brain, repetitive seizures also result in granule cell neurogenesis without loss of principal neurons. Although the relationship between these morphological changes after seizures during development and subsequent cognitive impairment is not yet clear, our findings indicate that during development recurrent seizures can result in significant alterations in cell number and axonal growth.}, Author = {Holmes, G. L. and Sarkisian, M. and Ben-Ari, Y. and Chevassus-Au-Louis, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Coloring Agents;Animals;Rats;Seizures;21 Epilepsy;Cell Count;Hippocampus;Rats, Wistar;Pentylenetetrazole;Behavior, Animal;Mossy Fibers, Hippocampal;Research Support, U.S. Gov't, P.H.S.;Histocytochemistry;21 Neurophysiology;Dentate Gyrus;Convulsants;24 Pubmed search results 2008;Recurrence;Research Support, Non-U.S. Gov't}, Medline = {99140495}, Month = {2}, Nlm_Id = {0406041}, Number = {4}, Organization = {Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, USA. holmesg\@a1.tch.harvard.edu}, Pages = {537-53}, Pii = {10.1002/(SICI)1096-9861(19990222)404:4<537::AID-CNE9>3.0.CO;2-#}, Pubmed = {9987996}, Title = {Mossy fiber sprouting after recurrent seizures during early development in rats}, Uuid = {A5F464BF-9077-4237-B296-EE0B2FA55F82}, Volume = {404}, Year = {1999}} @article{Holmes:2004, Abstract = {Running activity increases cell proliferation and neurogenesis in the dentate gyrus of adult mice. The present experiment was designed to investigate whether the effect of activity on adult neurogenesis is dependent on the time of day (circadian phase) and the amount of activity. Mice received restricted access to a running wheel (0, 1, or 3 hr) at one of three times of day: the middle of the light phase (i.e., when mice are normally inactive), dark onset (i.e., when mice begin their nocturnal activity), and the middle of the dark period (i.e., when mice are in the middle of their active period). Cell proliferation and net neurogenesis were assessed after incorporation of the thymidine analog bromodeoxyuridine (BrdU) and immunohistochemical detection of BrdU and neuronal markers. Running activity significantly increased cell proliferation, cell survival, and total number of new neurons only in animals with 3 hr of wheel access during the middle of the dark period. Although activity was positively correlated with increased neurogenesis at all time points, the effects were not statistically significant in animals with wheel access at the beginning of the dark period or during the middle of the light period. These data suggest that the influence of exercise on cell proliferation and neurogenesis is modulated by both circadian phase and the amount of daily exercise, thus providing new insight into the complex relationship between physiological and behavioral factors that can mediate adult neuroplasticity.}, Author = {Holmes, Melissa M. and Galea, Liisa A. M. and Mistlberger, Ralph E. and Kempermann, Gerd}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Animals;Astrocytes;Running;Physical Conditioning, Animal;Cell Count;Hippocampus;Mice, Inbred C57BL;Behavior, Animal;Time Factors;Male;Support, Non-U.S. Gov't;Neurons;04 Adult neurogenesis factors;Mice;Cell Division;Immunohistochemistry;Bromodeoxyuridine;Circadian Rhythm}, Month = {4}, Nlm_Id = {7600111}, Number = {2}, Organization = {Department of Psychology, University of British Columbia, Vancouver, British Columbia, Canada. holmes22\@msu.edu}, Pages = {216-22}, Pubmed = {15048919}, Title = {Adult hippocampal neurogenesis and voluntary running activity: circadian and dose-dependent effects}, Uuid = {91EBDE72-94BF-4D0C-A103-0CD5A5AC9104}, Volume = {76}, Year = {2004}, url = {papers/Holmes_JNeurosciRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20039}} @article{Holmes:2003, Author = {Holmes, Gregory L. and Ben-Ari, Yezekiel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {Genetic Vectors;Epilepsy;Galanin;21 Epilepsy;21 Neurophysiology;Rats;Fibronectins;comment;Gene Therapy;Humans;Animals;24 Pubmed search results 2008;Neurons;news}, Medline = {22775888}, Month = {8}, Nlm_Id = {9502015}, Number = {8}, Pages = {994-6}, Pii = {nm0803-994}, Pubmed = {12894158}, Title = {Seizing hold of seizures}, Uuid = {5B20AEF9-E824-4D01-944A-EF70B1D972AD}, Volume = {9}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm0803-994}} @article{Holmes:2002, Abstract = {The immature brain is more prone to seizures than the older brain as a result of an imbalance between excitatory and inhibitory input. The depolarizing, rather than hyperpolarizing effect of GABA(A) during the first week of life in the rodent, and the delay in postsynaptic GABA(B) inhibition coupled with the over-expression of glutamatergic synapses contribute to this increased propensity toward seizures. It is now clear that seizures can be injurious to the immature brain, although the pattern of seizure-induced injury is age-related. While the immature brain is resistant to acute seizure-induced cell loss, there are functional abnormalities following seizures with impairment of visual-spatial memory and reduced seizure threshold. Neonatal seizures are also associated with a number of activity-dependent changes in brain development including altered synaptogenesis and reduction in neurogenesis. These results argue that neonatal seizures should no longer be considered as benign events.}, Author = {Holmes, Gregory L. and Khazipov, Roustem and Ben-Ari, Yehezkiel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Disease Susceptibility;21 Epilepsy;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;Seizures;Animals, Newborn;Animals;Humans;Brain;Infant, Newborn;review}, Medline = {21921663}, Month = {1}, Nlm_Id = {9100935}, Number = {1}, Organization = {Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children's Hospital, Boston, MA 02115, USA.}, Pages = {A3-8}, Pubmed = {11924904}, Title = {New concepts in neonatal seizures}, Uuid = {4456B47A-5ABD-4D83-8FD6-CE05EB0F9531}, Volume = {13}, Year = {2002}} @article{Holmes:2002a, Abstract = {A considerable amount of money and effort is spent every year investigating the effects of seizure on the developing rodent brain. A critical question is the relevance of these studies to children. The goal of this chapter is to review the relationship between seizures during early development and cognitive impairment in children and rodents. While the majority of children with epilepsy have normal cognitive development, a small group of children with frequent, recurrent seizures show progressive cognitive impairment. Likewise, in rodent models recurrent seizures during early development are associated with cognitive impairment and histological changes including mossy fiber sprouting and reduced neurogenesis. Status epilepticus is associated with a lower morbidity and mortality rate in children than in adults. Status epilepticus in rodent models is associated with less cell loss and cognitive impairment than in adults. While rodent studies can offer a great deal of insight into mechanisms of seizure-induced brain damage, they also have significant limitations. No animal models have yet been developed that mimic human epileptic syndromes, such as infantile spasms, Lennox-Gastaut syndrome, or the severe myoclonic epilepsies. In addition, rodent studies supply only crude measures of learning and memory. Disturbances of language or higher cortical functions such as visual or auditory processing cannot be tested in animal models.}, Author = {Holmes, Gregory L. and Khazipov, Rustem and Ben-Ari, Yehezkiel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0079-6123}, Journal = {Prog Brain Res}, Keywords = {Disease Models, Animal;21 Epilepsy;Nerve Fibers;Research Support, Non-U.S. Gov't;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;Status Epilepticus;Seizures;Child;Maze Learning;Humans;Brain;24 Pubmed search results 2008;Animals;review}, Medline = {22139322}, Nlm_Id = {0376441}, Organization = {Department of Neurology, Harvard Medical School, Center for Research in Pediatric Epilepsy, Children's Hospital, Boston, MA 02115, USA. gregory.holmes\@tch.harvard.edu}, Pages = {321-34}, Pubmed = {12143352}, Title = {Seizure-induced damage in the developing human: relevance of experimental models}, Uuid = {0D537617-1003-44EA-8FFC-94025B833FB0}, Volume = {135}, Year = {2002}} @article{Holmgren:2003, Abstract = {The extent to which neocortical pyramidal cells function as a local network is determined by the strength and probability of their connections. By mapping connections between pyramidal cells we show here that in a local network of about 600 pyramidal cells located within a cylindrical volume of 200 microm x 200 microm of neocortical layer 2/3, an individual pyramidal cell receives synaptic inputs from about 30 other pyramidal neurons, with the majority of EPSP amplitudes in the 0.2-1.0 mV range. The probability of connection decreased from 0.09 to 0.01 with intercell distance (over the range 25-200 microm). Within the same volume, local interneuron (fast-spiking non-accommodating interneuron, FS)-pyramidal cell connections were about 10 times more numerous, with the majority of connections being reciprocal. The probability of excitatory and inhibitory connections between pyramidal cells and FS interneurons decreased only slightly with distance, being in the range 0.5-0.75. Pyramidal cells in the local network received strong synaptic input during stimulation of afferent fibres in layers 1 and 6. Minimal-like stimulation of layer 1 or layer 6 inputs simultaneously induced postsynaptic potentials in connected pyramidal cells as well as in pyramidal-FS cell pairs. These inputs readily induced firing of pyramidal cells, although synaptically connected cells displayed different firing patterns. Unitary EPSPs in pyramidal-pyramidal cell pairs did not detectably alter cell firing. FS interneurons fire simultaneously with pyramidal cells. In pyramidal-FS cell pairs, both unitary EPSPs and IPSPs efficiently modulated cell firing patterns. We suggest that computation in the local network may proceed not only by direct pyramidal-pyramidal cell communication but also via local interneurons. With such a high degree of connectivity with surrounding pyramidal cells, local interneurons are ideally poised to both coordinate and expand the local pyramidal cell network via pyramidal-interneuron-pyramidal communication.}, Author = {Holmgren, Carl and Harkany, Tibor and Svennenfors, Bj{\"o}rn and Zilberter, Yuri}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Signal Transduction;Electric Stimulation;Animals;Synapses;Rats;Afferent Pathways;Neocortex;Cell Communication;Rats, Sprague-Dawley;in vitro ;Pyramidal Cells;Axons;Dendrites;research support, non-u.s. gov't ;Nerve Net;Action Potentials;21 Neurophysiology;Interneurons;24 Pubmed search results 2008;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {0266262}, Number = {Pt 1}, Organization = {Karolinska Institute, Department of Neuroscience, Retzius v{\"a}g 8, B2-2, S-17177 Stockholm, Sweden.}, Pages = {139-53}, Pii = {jphysiol.2003.044784}, Pubmed = {12813147}, Title = {Pyramidal cell communication within local networks in layer 2/3 of rat neocortex}, Uuid = {4429603C-1779-4F55-9DDF-6C7FF7FD0B1C}, Volume = {551}, Year = {2003}, url = {papers/Holmgren_JPhysiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2003.044784}} @article{Holter:1991, Abstract = {Experimental gene transfer and viral infections can result in the accumulation of unintegrated DNA in target cells. The effects of such accumulation on target cell metabolism have not been directly studied. The experiments reported in this paper show that transfection of cloned retroviral long-terminal-repeat (LTR) DNA, or of a variety of eukaryotic promoters, into proliferating HeLa cells results in rapid, sequence-specific, and dose-dependent cell death. Plasmids containing the Rous sarcoma virus LTR or the human immunodeficiency virus LTR cloned in pUC-related plasmids are 5 to 10 times more toxic than pUC19. The demonstrated sensitivity of eukaryotic cells to exogenously introduced DNA has important implications for the interpretation of gene transfer experiments and may be relevant to the pathogenic mechanisms in the course of retroviral infections such as AIDS.}, Author = {Holter, W. and Rabson, A. B. and Corsico, C. D. and Howard, B. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0014-4827}, Journal = {Exp Cell Res}, Keywords = {Cell Survival;Research Support, Non-U.S. Gov't;HIV;Cytopathogenic Effect, Viral;Humans;Repetitive Sequences, Nucleic Acid;Transfection;HIV Long Terminal Repeat;15 Retrovirus mechanism;23 Technique;Retroviridae;Hela Cells;Research Support, U.S. Gov't, P.H.S.;Sarcoma Viruses, Avian;DNA, Viral;Receptors, Interleukin-2;Promoter Regions (Genetics);24 Pubmed search results 2008;Transcription, Genetic}, Medline = {91138647}, Month = {3}, Nlm_Id = {0373226}, Number = {1}, Organization = {Laboratory of Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.}, Pages = {54-8}, Pubmed = {1847335}, Title = {Sequence-specific toxicity of transfected retroviral DNA}, Uuid = {CE59C305-DC38-4F12-92EA-FC89DE1083E7}, Volume = {193}, Year = {1991}} @article{Holthoff:2006, Abstract = {Whereas the regenerative nature of action potential conduction in axons has been known since the late 1940s, neuronal dendrites have been considered as passive cables transferring incoming synaptic activity to the soma. The relatively recent discovery that neuronal dendrites contain active conductances has revolutionized our view of information processing in neurons. In many neuronal cell types, sodium action potentials initiated at the axon initial segment can back-propagate actively into the dendrite thereby serving, for the dendrite, as an indicator of the output activity of the neuron. In addition, the dendrites themselves can initiate action-potential-like regenerative responses, so-called dendritic spikes, that are mediated either by the activation of sodium, calcium, and/or N-methyl-D-aspartate receptor channels. Here, we review the recent experimental and theoretical evidence for a role of regenerative dendritic activity in information processing within neurons and, especially, in activity-dependent synaptic plasticity.}, Author = {Holthoff, Knut and Kovalchuk, Yury and Konnerth, Arthur}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0302-766X}, Journal = {Cell Tissue Res}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {0417625}, Number = {2}, Organization = {Institute of Neuroscience, Technical University Munich, Biedersteinerstrasse 29, 80802, Munich, Germany, knut.holthoff\@lrz.tu-muenchen.de.}, Pages = {369-77}, Pubmed = {16816965}, Title = {Dendritic spikes and activity-dependent synaptic plasticity}, Uuid = {AC76AE20-028F-462C-9187-9C2B9947B326}, Volume = {326}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00441-006-0263-8}} @article{Holthoff:2002, Abstract = {Dendritic spines are morphologically and functionally heterogeneous. To understand this diversity, we use two-photon imaging of layer 5 neocortical pyramidal cells and measure action potential-evoked [Ca(2+)]i transients in spines. Spine calcium kinetics are controlled by (i) the diameter of the parent dendrite, (ii) the length of the spine neck, and (iii) the strength of spine calcium pumps. These factors produce different calcium dynamics in spines from basal, proximal apical, and distal apical dendrites, differences that are more pronounced without exogenous buffers. In proximal and distal apical dendrites, different calcium dynamics correlate with different susceptibility to synaptic depression, and modifying calcium kinetics in spines changes the expression of long-term depression. Thus, the spine location apparently determines its calcium dynamics and synaptic plasticity. Our results highlight the precision in design of neocortical neurons.}, Author = {Holthoff, Knut and Tsay, David and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Fluorescent Dyes;Animals;In Vitro;Neuronal Plasticity;Microscopy, Confocal;Patch-Clamp Techniques;Models, Biological;Pyramidal Cells;Calcium;21 Calcium imaging;Dendrites;Mathematics;Statistics;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Mice;24 Pubmed search results 2008;Visual Cortex;Models, Neurological;Research Support, Non-U.S. Gov't}, Medline = {21822663}, Month = {1}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department Biological Sciences, Columbia University, New York, NY 10027, USA. holthoff\@irz.uni-muenchen.de}, Pages = {425-37}, Pii = {S0896627302005767}, Pubmed = {11832229}, Title = {Calcium dynamics of spines depend on their dendritic location}, Uuid = {E924BD75-C3A8-421A-B0AF-EF005BF444E6}, Volume = {33}, Year = {2002}} @article{Holtmaat:2005, Abstract = {Dendritic spines were imaged over days to months in the apical tufts of neocortical pyramidal neurons (layers 5 and 2/3) in vivo. A fraction of thin spines appeared and disappeared over a few days, while most thick spines persisted for months. In the somatosensory cortex, from postnatal day (PND) 16 to PND 25 spine retractions exceeded additions, resulting in a net loss of spines. The fraction of persistent spines (lifetime > or = 8 days) grew gradually during development and into adulthood (PND 16-25, 35\%; PND 35-80, 54\%; PND 80-120, 66\%; PND 175-225, 73\%), providing evidence that synaptic circuits continue to stabilize even in the adult brain, long after the closure of known critical periods. In 6-month-old mice, spines turn over more slowly in visual compared to somatosensory cortex, possibly reflecting differences in the capacity for experience-dependent plasticity in these brain regions.}, Author = {Holtmaat, Anthony J. G. D. and Trachtenberg, Joshua T. and Wilbrecht, Linda and Shepherd, Gordon M. and Zhang, Xiaoqun and Knott, Graham W. and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Cell Differentiation;Animals;Synapses;Aging;Neuronal Plasticity;Neural Pathways;10 Structural plasticity;Neocortex;Dendritic Spines;Mice, Transgenic;Pyramidal Cells;Mice, Inbred C57BL;Microscopy, Fluorescence;Green Fluorescent Proteins;Male;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Somatosensory Cortex;Mice;24 Pubmed search results 2008;Visual Cortex;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {8809320}, Number = {2}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.}, Pages = {279-91}, Pii = {S0896627305000048}, Pubmed = {15664179}, Title = {Transient and persistent dendritic spines in the neocortex in vivo}, Uuid = {F7868304-A7AB-4F14-91A1-01287F624B4F}, Volume = {45}, Year = {2005}, url = {papers/Holtmaat_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.01.003}} @article{Honda:2004, Abstract = {The mechanism of topographic mapping of retinal ganglion cells to the midbrain was previously elucidated by the servomechanism model, which is based on the fact that cells expressing Eph-receptors respond specifically to surface expressing membrane-bound ephrin-ligands at a critical level. The retina has increased nasal-to-temporal gradient of Eph receptor-density, and the optic tectum/superior colliculus has increased rostral-to-caudal gradient of membrane-bound ephrin-ligand. An axon from the retina has an identification tag of a certain level of Eph-receptor density depending on its retinal position, and adheres to the site on the tectum/superior colliculus expressing ephrin-ligands at a critical ligand-density level. The servomechanism model rigidly defines positions of axon terminals on the midbrain. However, optic nerve regeneration experiments combined with halved retina or tectum show a plastic or flexible mapping (expansion, compression and transposition of tectal projections). To reconcile the discrepancy between the rigid model and the plastic behavior, competition between retinal axon terminals for a target site was introduced to the servomechanism. The servomechanism/competition model succeeded in computer simulations of the plastic mapping of retinal axons on the tectum. Recent experiments of upregulated ligand-density on the tectum during nerve regeneration and the role of axonal competition are discussed.}, Author = {Honda, Hisao}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0012-1592}, Journal = {Dev Growth Differ}, Keywords = {10 Development;research support, non-u.s. gov't;21 Neurophysiology;Neuronal Plasticity;Algorithms;10 circuit formation;21 Activity-development;Computer Simulation;Retinal Ganglion Cells;Animals;Mice;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0356504}, Number = {5}, Organization = {Hyogo University, Kakogawa, Hyogo 675-0195, Japan. hihonda\@hyogo-dai.ac.jp}, Pages = {425-37}, Pii = {DGD759}, Pubmed = {15606488}, Title = {Competitive interactions between retinal ganglion axons for tectal targets explain plasticity of retinotectal projection in the servomechanism model of retinotectal mapping}, Uuid = {B87CB708-836A-410C-886D-C5A364A6B8F7}, Volume = {46}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1440-169x.2004.00759.x}} @article{Honda:1990, Abstract = {Employing immunohistochemical techniques and a panel of monoclonal antibodies that recognize rat cells of monocyte/macrophage lineage, we have demonstrated that cells labeled with these antibodies are widely distributed throughout the parenchyma of the rat brain. These cells have a remarkable microglial morphology and form phenotypically heterogenous populations. Double immunoperoxidase staining with the monoclonal antibody and anti-von Willebrand factor antiserum, which recognizes vascular endothelial cells, revealed that these cells are located exclusively at perivascular sites in the adult brain. These observations indicate that the microglial cells are perivascular cells of the monocyte/macrophage lineage, and may be intimately involved in various immunopathogenic conditions of the central nervous system.}, Author = {Honda, H. and Kimura, H. and Silvers, W. K. and Rostami, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Monocytes;Research Support, Non-U.S. Gov't;Rats, Inbred Lew;Neuroglia;Rats;Immunohistochemistry;Research Support, U.S. Gov't, P.H.S.;Antibodies, Monoclonal;T-Lymphocytes;Phenotype;11 Glia;Antigens, CD4;Macrophages;Blood Vessels;Animals;Brain}, Medline = {91009779}, Nlm_Id = {8109498}, Number = {1-3}, Organization = {Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104.}, Pages = {183-91}, Pubmed = {2104520}, Title = {Perivascular location and phenotypic heterogeneity of microglial cells in the rat brain}, Uuid = {3B5146DE-CAA0-4705-8FC0-F32B036B21A3}, Volume = {29}, Year = {1990}} @article{Honda:2003, Abstract = {Topographic mapping of retinal ganglion axons to the midbrain is computed by the servomechanism model, which is based on the experimental result of cell attachment. Cells expressing a certain level of Eph proteins (receptors for ephrin ligands) optimally attach to a surface that expresses a specific level of ephrin ligand density. The retina has an increasing nasal-to-temporal gradient of Eph receptor density, and the optic tectum/superior colliculus has an increasing rostral-to-caudal gradient of membrane-bound ephrin ligand. An axon from the retina has an identification tag of a certain level of Eph receptor density depending on its retinal position and adheres to the site on the tectum/superior colliculus expressing ephrin ligands at a critical ligand density level. Quantitatively, a retinal axon has a receptor density (R) that is determined by its retinal position, and the axon terminal is induced to adhere to the tectal site of ligand density (L = S/R), where S is a constant. Consequently, the servomechanism model defines positions of axon terminals on the midbrain. Abnormal topographic maps are reported in a knock-in experiment with elevated density of Eph receptors and a knock-out experiment lacking ephrin ligands using gene-targeting technology. By adding competition between axon terminals for target sites to the servomechanism model, the abnormal maps became easy to understand. Furthermore, the servomechanism-competition model allowed conjecture of the gradient shapes of receptor and ligand densities and estimation of the capacity of the midbrain surface to accept retinal axon terminals.}, Author = {Honda, Hisao}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Retina;10 Development;Heterozygote;Animals;Ephrins;Superior Colliculi;09 Evolutionary dynamics;Axons;Mice, Transgenic;research support, non-u.s. gov't;10 circuit formation;Computer Simulation;Mice, Knockout;21 Neurophysiology;Homozygote;21 Activity-development;Mice;24 Pubmed search results 2008;Receptor, EphA1;Models, Neurological;Ligands;Retinal Ganglion Cells}, Month = {11}, Nlm_Id = {8102140}, Number = {32}, Organization = {Hyogo University, Hyogo 675-0195, Japan. hihonda\@hyogo-dai.ac.jp}, Pages = {10368-77}, Pii = {23/32/10368}, Pubmed = {14614096}, Title = {Competition between retinal ganglion axons for targets under the servomechanism model explains abnormal retinocollicular projection of Eph receptor-overexpressing or ephrin-lacking mice}, Uuid = {0A5DCF95-65A4-4551-AC9C-A3A3EA613455}, Volume = {23}, Year = {2003}, url = {papers/Honda_JNeurosci2003.pdf}} @article{Honda:1999, Abstract = {The neurotrophic effect of glial cell line-derived neurotrophic factor (GDNF) has been well documented in both the central and peripheral nervous systems. From the histological findings, target cells of GDNF have been considered to be neurons. In the present study, the expression of GDNF receptors, ret and GFRalpha-1, was demonstrated in rat primary cultured microglia by reverse transcription-polymerase chain reaction and the protein-level expression of Ret was also confirmed by Western-blotting analyses. Moreover, GDNF stimulated the phosphorylation of MAP kinase (ERK1/2) in the cells. These results suggest that GDNF regulates not only neuronal survival and maturation but also certain functions of microglia in the brain.}, Author = {Honda, S. and Nakajima, K. and Nakamura, Y. and Imai, Y. and Kohsaka, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {p42 MAP Kinase;Animals;Cells, Cultured;Rats;Microglia;Kinetics;RNA, Messenger;Not relevant;11 Glia;Nerve Growth Factors;Support, Non-U.S. Gov't;Animals, Newborn;Cerebral Cortex;Polymerase Chain Reaction;Receptor Protein-Tyrosine Kinases;Proto-Oncogene Proteins;Nerve Tissue Proteins;Drosophila Proteins;Mitogen-Activated Protein Kinases;Transcription, Genetic}, Medline = {20046677}, Month = {11}, Nlm_Id = {7600130}, Number = {3}, Organization = {Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo, Japan.}, Pages = {203-6}, Pii = {S0304394099007697}, Pubmed = {10580710}, Title = {Rat primary cultured microglia express glial cell line-derived neurotrophic factor receptors}, Uuid = {09C55A16-0AD5-4080-BC31-2D8BEFE241B6}, Volume = {275}, Year = {1999}, url = {papers/Honda_NeurosciLett1999.pdf}} @article{Honey:2007, Abstract = {Neuronal dynamics unfolding within the cerebral cortex exhibit complex spatial and temporal patterns even in the absence of external input. Here we use a computational approach in an attempt to relate these features of spontaneous cortical dynamics to the underlying anatomical connectivity. Simulating nonlinear neuronal dynamics on a network that captures the large-scale interregional connections of macaque neocortex, and applying information theoretic measures to identify functional networks, we find structure-function relations at multiple temporal scales. Functional networks recovered from long windows of neural activity (minutes) largely overlap with the underlying structural network. As a result, hubs in these long-run functional networks correspond to structural hubs. In contrast, significant fluctuations in functional topology are observed across the sequence of networks recovered from consecutive shorter (seconds) time windows. The functional centrality of individual nodes varies across time as interregional couplings shift. Furthermore, the transient couplings between brain regions are coordinated in a manner that reveals the existence of two anticorrelated clusters. These clusters are linked by prefrontal and parietal regions that are hub nodes in the underlying structural network. At an even faster time scale (hundreds of milliseconds) we detect individual episodes of interregional phase-locking and find that slow variations in the statistics of these transient episodes, contingent on the underlying anatomical structure, produce the transfer entropy functional connectivity and simulated blood oxygenation level-dependent correlation patterns observed on slower time scales.}, Author = {Honey, Christopher J. and K{\"o}tter, Rolf and Breakspear, Michael and Sporns, Olaf}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2014-08-05 13:06:21 +0000}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Visual Cortex;Computational Biology;research support, non-u.s. gov't;21 Neurophysiology;Motor Cortex;Models, Neurological;Neural Pathways;Neocortex;Time Factors;Nerve Net;Animals;Macaca;24; Cerebral Cortex;Somatosensory Cortex; network; technique; Methods; review literature; computation biology; Theoretical; graph theory; human; fmri; Software}, Month = {6}, Nlm_Id = {7505876}, Number = {24}, Organization = {Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.}, Pages = {10240-5}, Pii = {0701519104}, Pubmed = {17548818}, Title = {Network structure of cerebral cortex shapes functional connectivity on multiple time scales}, Uuid = {F9E66FE9-A014-4D12-8A22-9D419B276564}, Volume = {104}, Year = {2007}, url = {papers/Honey_ProcNatlAcadSciUSA2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0701519104}} @article{Hong:2005, Abstract = {Cognitive development is determined by both genetics and environment. One point of convergence of these two influences is the neural activity-dependent regulation of programs of gene expression that specify neuronal fate and function. Human genetic studies have linked several transcriptional regulators to neurodevelopmental disorders including mental retardation and autism spectrum disorders. Recent reports on two such factors, CREB-binding protein and methyl-CpG-binding protein 2, have begun to reveal how epigenetics and neuronal activity act to modulate the program of gene expression required for synaptic development and function.}, Author = {Hong, Elizabeth J. and West, Anne E. and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Cognition Disorders;21 Neurophysiology;Transcription, Genetic;Cognition;Humans;Animals;24 Pubmed search results 2008;review;Transcription Factors}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Division of Neuroscience, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {21-8}, Pii = {S0959-4388(05)00003-6}, Pubmed = {15721740}, Title = {Transcriptional control of cognitive development}, Uuid = {5A4F74D5-899E-4B0C-88AE-B473DAE293A7}, Volume = {15}, Year = {2005}, url = {papers/Hong_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.01.002}} @article{Hong:2000, Abstract = {Normal development of the cerebral cortex requires long-range migration of cortical neurons from proliferative regions deep in the brain. Lissencephaly ("smooth brain," from "lissos," meaning smooth, and "encephalos," meaning brain) is a severe developmental disorder in which neuronal migration is impaired, leading to a thickened cerebral cortex whose normally folded contour is simplified and smooth. Two identified lissencephaly genes do not account for all known cases, and additional lissencephaly syndromes have been described. An autosomal recessive form of lissencephaly (LCH) associated with severe abnormalities of the cerebellum, hippocampus and brainstem maps to chromosome 7q22, and is associated with two independent mutations in the human gene encoding reelin (RELN). The mutations disrupt splicing of RELN cDNA, resulting in low or undetectable amounts of reelin protein. LCH parallels the reeler mouse mutant (Reln(rl)), in which Reln mutations cause cerebellar hypoplasia, abnormal cerebral cortical neuronal migration and abnormal axonal connectivity. RELN encodes a large (388 kD) secreted protein that acts on migrating cortical neurons by binding to the very low density lipoprotein receptor (VLDLR), the apolipoprotein E receptor 2 (ApoER2; refs 9-11 ), alpha3beta1 integrin and protocadherins. Although reelin was previously thought to function exclusively in brain, some humans with RELN mutations show abnormal neuromuscular connectivity and congenital lymphoedema, suggesting previously unsuspected functions for reelin in and outside of the brain.}, Author = {Hong, S. E. and Shugart, Y. Y. and Huang, D. T. and Shahwan, S. A. and Grant, P. E. and Hourihane, J. O. and Martin, N. D. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Brain Stem;24 Pubmed search results 2008;Male;Models, Genetic;Cerebral Cortex;10 Development;Animals;Linkage (Genetics);Hippocampus;Phenotype;Extracellular Matrix Proteins;Chromosomes, Human, Pair 7;Magnetic Resonance Imaging;research support, u.s. gov't, p.h.s.;Chromosome Mapping;Lod Score;Frameshift Mutation;Mutation;Serine Endopeptidases;Blotting, Western;Microsatellite Repeats;RNA Splicing;Cerebellum;Pedigree;Female;Cell Adhesion Molecules, Neuronal;Family Health;DNA, Complementary;research support, non-u.s. gov't;Mice;Genes, Recessive;Humans;Reverse Transcriptase Polymerase Chain Reaction;10 genetics malformation;Nerve Tissue Proteins}, Month = {9}, Nlm_Id = {9216904}, Number = {1}, Organization = {Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts, USA.}, Pages = {93-6}, Pubmed = {10973257}, Title = {Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutations}, Uuid = {63D251FC-1EAE-48E3-BDD5-978BA32CFA29}, Volume = {26}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/79246}} @article{Hoopfer:2006, Abstract = {Axon pruning by degeneration remodels exuberant axonal connections and is widely required for the development of proper circuitry in the nervous system from insects to mammals. Developmental axon degeneration morphologically resembles injury-induced Wallerian degeneration, suggesting similar underlying mechanisms. As previously reported for mice, we show that Wlds protein substantially delays Wallerian degeneration in flies. Surprisingly, Wlds has no effect on naturally occurring developmental axon degeneration in flies or mice, although it protects against injury-induced degeneration of the same axons at the same developmental age. By contrast, the ubiquitin-proteasome system is intrinsically required for both developmental and injury-induced axon degeneration. We also show that the glial cell surface receptor Draper is required for efficient clearance of axon fragments during developmental axon degeneration, similar to its function in injury-induced degeneration. Thus, mechanistically, naturally occurring developmental axon pruning by degeneration and injury-induced axon degeneration differ significantly in early steps, but may converge onto a common execution pathway.}, Author = {Hoopfer, Eric D. and McLaughlin, Todd and Watts, Ryan J. and Schuldiner, Oren and O'Leary, Dennis D. M. and Luo, Liqun}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Gene Expression Regulation, Developmental;10 Development;research support, n.i.h., extramural ;Wallerian Degeneration;Nerve Tissue Proteins;Animals, Genetically Modified;Drosophila Proteins;Mice, Inbred C57BL;Drosophila;10 Structural plasticity;Animals;comparative study ;Mice;24 Pubmed search results 2008;Axons}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Howard Hughes Medical Institute, Department of Biological Sciences and Neurosciences Program, Stanford University, 385 Serra Mall, Stanford, California 94305, USA.}, Pages = {883-95}, Pii = {S0896-6273(06)00380-1}, Pubmed = {16772170}, Title = {Wlds protection distinguishes axon degeneration following injury from naturally occurring developmental pruning}, Uuid = {AEDC064D-5D0E-4823-8D0D-0637AEAF392F}, Volume = {50}, Year = {2006}, url = {papers/Hoopfer_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.05.013}} @article{Hopfield:1982, Abstract = {Computational properties of use of biological organisms or to the construction of computers can emerge as collective properties of systems having a large number of simple equivalent components (or neurons). The physical meaning of content-addressable memory is described by an appropriate phase space flow of the state of a system. A model of such a system is given, based on aspects of neurobiology but readily adapted to integrated circuits. The collective properties of this model produce a content-addressable memory which correctly yields an entire memory from any subpart of sufficient size. The algorithm for the time evolution of the state of the system is based on asynchronous parallel processing. Additional emergent collective properties include some capacity for generalization, familiarity recognition, categorization, error correction, and time sequence retention. The collective properties are only weakly sensitive to details of the modeling or the failure of individual devices.}, Author = {Hopfield, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Computers;20 Networks;Mathematics;Models, Neurological;Memory;research support, u.s. gov't, non-p.h.s.;Animals;24 Pubmed search results 2008;Neurons}, Month = {4}, Nlm_Id = {7505876}, Number = {8}, Pages = {2554-8}, Pubmed = {6953413}, Title = {Neural networks and physical systems with emergent collective computational abilities}, Uuid = {6083F25D-690C-49ED-BECB-EE6AB3B1B55B}, Volume = {79}, Year = {1982}, url = {papers/Hopfield_ProcNatlAcadSciUSA1982.pdf}} @article{Hori:2001, Abstract = {PURPOSE. To determine the extent to which donor cells persist and recipient cells repopulate each of the three cell layers of orthotopic corneal grafts in mice. METHODS. BALB/c, C57BL/6, and enhanced green fluorescence protein (EGFP) transgenic mice (B6 background) were used as donors and recipients for orthotopic syngeneic and allogeneic corneal grafts. Graft-bearing eyes were harvested at 5, 10, 15, 28, and 56 days, stained with propidium iodide, and observed (layer by layer) by confocal microscopy. Bone marrow-derived cells in the grafts were assessed immunohistochemically. RESULTS. Donor epithelium was totally replaced by recipient epithelial cells within 15 days in both syngeneic and allogeneic grafts, whereas donor stromal keratocytes and endothelial cells were retained virtually intact in syngeneic grafts and in accepted allografts. In rejected allografts, neither donor-derived keratocytes nor endothelial cells were detected, and, instead, recipient-derived stromal fibroblasts, neovessels, and infiltrating leukocytes were heavily represented. The posterior surface of rejected grafts was devoid of corneal endothelium and was covered incompletely with bone marrow-derived cells of recipient origin. CONCLUSIONS. Whereas in mice graft-derived epithelium is largely irrelevant to corneal allograft outcome, persistence of donor-derived endothelium and keratocytes correlates perfectly with graft acceptance. Recipient endothelium is incapable of covering the posterior surface of accepted or rejected corneal grafts, whereas bone marrow-derived cells of recipient origin come to occupy this site in rejected grafts.}, Author = {Hori, J. and Streilein, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0146-0404}, Journal = {Invest Ophthalmol Vis Sci}, Keywords = {Cell Survival;Research Support, Non-U.S. Gov't;Keratoplasty, Penetrating;Animals;Mice, Inbred BALB C;Microscopy, Confocal;Fibroblasts;Cell Count;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Corneal Stroma;Microscopy, Fluorescence;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Transplantation, Homologous;Graft Rejection;Tissue Donors;Mice;Luminescent Proteins;Endothelium, Corneal;Epithelium, Corneal}, Medline = {21324520}, Month = {7}, Nlm_Id = {7703701}, Number = {8}, Organization = {Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114-2500, USA.}, Pages = {1820-8}, Pubmed = {11431448}, Title = {Dynamics of donor cell persistence and recipient cell replacement in orthotopic corneal allografts in mice}, Uuid = {4009C0FF-7634-4C33-B203-9C455A95B872}, Volume = {42}, Year = {2001}} @article{Horn:2002, Abstract = {Efficient transduction of hematopoietic stem cells is a prerequisite for successful hematopoietic stem cell gene therapy. Oncoretroviral vectors are the most widely used vectors for hematopoietic gene therapy studies. However, these vectors require cell division, and thus efficient transduction of quiescent stem cells has been difficult to achieve. Lentiviral vectors can transduce non-dividing cells and therefore may be more efficient in transducing quiescent hematopoietic stem cells. We have used a competitive repopulation assay in the baboon to compare transduction of hematopoietic repopulating cells by lentiviral and oncoretroviral vectors. Baboon CD34-enriched marrow cells were transduced in the presence or absence of multiple hematopoietic growth factors using a short, 2-day, transduction protocol. Here, we show that efficient lentiviral transduction of hematopoietic repopulating cells was only achieved when cells were transduced in the presence of multiple growth factors. Using these conditions, up to 8.6\%of hematopoietic repopulating cells were genetically modified by the lentiviral vector more than 1 year after transplant. Interestingly, the number of lentivirally marked cells increased over time in three of four animals. In conclusion, these results suggest that lentiviral vectors are able to tranduce multilineage hematopoietic stem cells, and thus, may provide an alternative vector system for clinical stem cell gene therapy applications.}, Author = {Horn, P. A. and Morris, J. C. and Bukovsky, A. A. and Andrews, R. G. and Naldini, L. and Kurre, P. and Kiem, H-P P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Transduction, Genetic;Animals;Hematopoietic Cell Growth Factors;Cells, Cultured;Stem Cell Transplantation;Comparative Study;Recombinant Proteins;Lentivirus;Antigens, CD34;11 Glia;Retroviridae;Green Fluorescent Proteins;Papio;Research Support, U.S. Gov't, P.H.S.;Gene Therapy;Polymerase Chain Reaction;Transplantation, Autologous;Hematopoietic Stem Cells;Luminescent Proteins;Models, Animal;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {22265326}, Month = {11}, Nlm_Id = {9421525}, Number = {21}, Organization = {Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.}, Pages = {1464-71}, Pubmed = {12378409}, Title = {Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons}, Uuid = {014DF188-FC7B-44C5-AA99-CD4685CCCB1E}, Volume = {9}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3301820}} @article{Horner:2002, Abstract = {The NG2 proteoglycan is believed to be an in vivo marker for oligodendrocyte progenitors found in the developing brain. The prevalence of NG2-expressing cells that remain in the adult CNS following the end of gliogenesis is significant. Current research is focused on how this cell participates in the normal function of the adult CNS and whether it may be activated by injury and/or contribute to repair. Despite substantial evidence for a sub-population of NG2-expressing cells playing a glial progenitor role in the adult CNS, there is much to be learned. Specifically, the heterogeneity of this population has not been adequately addressed for the adult CNS and while NG2 cells continue to divide in the adult CNS it is not clear what function they serve once myelination is complete. Future studies should elucidate the functional importance of NG2 in a variety of cell functions and shed light on the role NG2-expressing cells play in the intact and diseased CNS. 0300-4864 Journal Article}, Author = {Horner, P. J. and Thallmair, M. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurocytol}, Keywords = {11 Glia;G pdf}, Number = {6-7}, Organization = {Department of Neurological Surgery, University of Washington, 325 Ninth Ave Box 359655, Seattle, WA 98104, USA. phorner\@u.washington.edu}, Pages = {469-80}, Pubmed = {14501217}, Title = {Defining the NG2-expressing cell of the adult CNS}, Uuid = {A7903E18-3076-4402-9835-F686B182B0B1}, Volume = {31}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14501217}} @article{Horner:2000, Abstract = {The existence of multipotent progenitor populations in the adult forebrain has been widely studied. To extend this knowledge to the adult spinal cord we have examined the proliferation, distribution, and phenotypic fate of dividing cells in the adult rat spinal cord. Bromodeoxyuridine (BrdU) was used to label dividing cells in 13- to 14- week-old, intact Fischer rats. Single daily injections of BrdU were administered over a 12 d period. Animals were killed either 1 d or 4 weeks after the last injection of BrdU. We observed frequent cell division throughout the adult rodent spinal cord, particularly in white matter tracts (5-7\%of all nuclei). The majority of BrdU-labeled cells colocalized with markers of immature glial cells. At 4 weeks, 10\%of dividing cells expressed mature astrocyte and oligodendroglial markers. These data predict that 0.75\%of all astrocytes and 0.82\%of all oligodendrocytes are derived from a dividing population over a 4 week period. To determine the migratory nature of dividing cells, a single BrdU injection was given to animals that were killed 1 hr after the injection. In these tissues, the distribution and incidence of BrdU labeling matched those of the 4 week post injection (pi) groups, suggesting that proliferating cells divide in situ rather than migrate from the ependymal zone. These data suggest a higher level of cellular plasticity for the intact spinal cord than has previously been observed and that glial progenitors exist in the outer circumference of the spinal cord that can give rise to both astrocytes and oligodendrocytes.}, Author = {Horner, P. J. and Power, A. E. and Kempermann, G. and Kuhn, H. G. and Palmer, T. D. and Winkler, J. and Thal, L. J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurosci}, Keywords = {Salivary Proteins/analysis;Rats;Microscopy, Confocal;Stem Cells/chemistry/*cytology;Neurons/chemistry/*cytology;Animal;02 Adult neurogenesis migration;Astrocytes/chemistry/*cytology;Antimetabolites/analysis/pharmacokinetics;Spinal Cord/*cytology/growth &development;Male;BB abstr;03 Adult neurogenesis progenitor source;Oligodendroglia/chemistry/cytology;Rats, Inbred F344;Cell Division/physiology;Bromodeoxyuridine/analysis/pharmacokinetics;Support, Non-U.S. Gov't;Cell Nucleus;Support, U.S. Gov't, P.H.S.;Age Factors;Cell Movement/physiology;Cell Differentiation/physiology;Biological Markers}, Number = {6}, Organization = {The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA. fgage\@salk.edu}, Pages = {2218-28.}, Title = {Proliferation and differentiation of progenitor cells throughout the intact adult rat spinal cord}, Uuid = {6C0060C8-1782-4721-9DEB-CA9909D02DCE}, Volume = {20}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10704497%20http://www.jneurosci.org/cgi/content/full/20/6/2218%20http://www.jneurosci.org/cgi/content/abstract/20/6/2218}} @article{Horner:2000a, Abstract = {It is self-evident that the adult mammalian brain and spinal cord do not regenerate after injury, but recent discoveries have forced a reconsideration of this accepted principle. Advances in our understanding of how the brain develops have provided a rough blueprint for how we may bring about regeneration in the damaged brain. Studies in developmental neurobiology, intracellular signalling and neuroimmunology are bringing the regeneration field closer to success. Notwithstanding these advances, clear and indisputable evidence for adult functional regeneration remains to be shown.}, Author = {Horner, P. J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {Nature}, Keywords = {01 Adult neurogenesis general;A, L both;Nervous System/immunology/*injuries;Nervous System Diseases/pathology;Signal Transduction;Animal;Nerve Growth Factors/physiology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;*Nerve Regeneration;Axons}, Number = {6807}, Organization = {The Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA.}, Pages = {963-70.}, Title = {Regenerating the damaged central nervous system}, Uuid = {E01EED99-D590-4C56-94FC-7C7966800116}, Volume = {407}, Year = {2000}, url = {papers/Horner_Nature2000.pdf}} @article{Horner:2003, Abstract = {Like a newly popular nightspot, the biology of adult stem cells has emerged from obscurity to become one of the most lively new disciplines of the decade. The neurosciences have not escaped this trendy pastime and, from amid the noise and excitement, the astrocyte emerges as a beguiling companion to the adult neural stem cell. A once receding partner to neurons and oligodendrocytes, the astrocyte even takes on an alter ego of the stem cell itself (S. Goldman, this issue of TINS). Putting ego aside, the 'astrocyte' is also (and perhaps more importantly) an integral component of neural progenitor hotspots, where the craziness or 'la vida loca' of the nightlife might not be so wild when compared with our traditional understanding of the astrocyte. Here, astrocytes contribute to the instructive confluence of location, atmosphere and cellular neighbors that define the daily 'vida local' or everyday local life of an adult stem cell. This review discusses astrocytes as influential components in the local stem cell niche.}, Author = {Horner, Philip J. and Palmer, Theo D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {review;Neuroglia;Glial Fibrillary Acidic Protein;03 Adult neurogenesis progenitor source;Astrocytes;Stem Cells;Cell Division;11 Glia;review, tutorial;Animals;Cerebral Cortex;Cell Lineage;Neurons}, Medline = {22949173}, Month = {11}, Nlm_Id = {7808616}, Number = {11}, Organization = {University of Washington, Department of Neurosurgery, Harborview R&T Building, 325 Ninth Ave - Box 359655, Seattle, WA 98104, USA. tpalmer\@stanford.edu}, Pages = {597-603}, Pii = {S0166223603002935}, Pubmed = {14585599}, Title = {New roles for astrocytes: the nightlife of an 'astrocyte'. La vida loca!}, Uuid = {9353075F-1767-487C-AF7C-EB7B33616D4D}, Volume = {26}, Year = {2003}, url = {papers/Horner_TrendsNeurosci2003.pdf}} @article{Horowitz:1999, Abstract = {Mammalian nervous system function involves billions of neurons which are interconnected in a multitude of neural circuits. Here we describe a genetic approach to chart neural circuits. By using an olfactory- specific promoter, we selectively expressed barley lectin in sensory neurons in the olfactory epithelium and vomeronasal organ of transgenic mice. The lectin was transported through the axons of those neurons to the olfactory bulb, transferred to the bulb neurons with which they synapse, and transported through the axons of bulb neurons to the olfactory cortex. The lectin also was retrogradely transported from the bulb to neuromodulatory brain areas. No evidence could be obtained for adverse effects of the lectin on odorant receptor gene expression, sensory axon targeting in the bulb, or the generation or transmission of signals by olfactory sensory neurons. Transneuronal transfer was detected prenatally in the odor-sensing pathway, but only postnatally in the pheromone-sensing pathway, suggesting that odors, but not pheromones, may be sensed in utero. Our studies demonstrate that a plant lectin can serve as a transneuronal tracer when its expression is genetically targeted to a subset of neurons. This technology can potentially be applied to a variety of vertebrate and invertebrate neural systems and may be particularly valuable for mapping connections formed by small subsets of neurons and for studying the development of connectivity as it occurs in utero.}, Author = {Horowitz, L. F. and Montmayeur, J. P. and Echelard, Y. and Buck, L. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Gene Transfer Techniques;Neurons/*physiology;23 Technique;Brain/*physiology;Human;Biological Markers;T;Axonal Transport/*physiology;Animal;Lectins/genetics;Mice, Transgenic;Support, Non-U.S. Gov't;Mice;Plant Proteins/genetics;Nerve Net/*physiology}, Number = {6}, Organization = {Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {3194-9.}, Title = {A genetic approach to trace neural circuits}, Uuid = {4F8C43AE-39AD-41BC-B307-EDAEB7283D37}, Volume = {96}, Year = {1999}, url = {papers/Horowitz_ProcNatlAcadSciUSA1999}} @article{Horton:2005, Abstract = {This year, the field of neuroscience celebrates the 50th anniversary of Mountcastle's discovery of the cortical column. In this review, we summarize half a century of research and come to the disappointing realization that the column may have no function. Originally, it was described as a discrete structure, spanning the layers of the somatosensory cortex, which contains cells responsive to only a single modality, such as deep joint receptors or cutaneous receptors. Subsequently, examples of columns have been uncovered in numerous cortical areas, expanding the original concept to embrace a variety of different structures and principles. A "column" now refers to cells in any vertical cluster that share the same tuning for any given receptive field attribute. In striate cortex, for example, cells with the same eye preference are grouped into ocular dominance columns. Unaccountably, ocular dominance columns are present in some species, but not others. In principle, it should be possible to determine their function by searching for species differences in visual performance that correlate with their presence or absence. Unfortunately, this approach has been to no avail; no visual faculty has emerged that appears to require ocular dominance columns. Moreover, recent evidence has shown that the expression of ocular dominance columns can be highly variable among members of the same species, or even in different portions of the visual cortex in the same individual. These observations deal a fatal blow to the idea that ocular dominance columns serve a purpose. More broadly, the term "column" also denotes the periodic termination of anatomical projections within or between cortical areas. In many instances, periodic projections have a consistent relationship with some architectural feature, such as the cytochrome oxidase patches in V1 or the stripes in V2. These tissue compartments appear to divide cells with different receptive field properties into distinct processing streams. However, it is unclear what advantage, if any, is conveyed by this form of columnar segregation. Although the column is an attractive concept, it has failed as a unifying principle for understanding cortical function. Unravelling the organization of the cerebral cortex will require a painstaking description of the circuits, projections and response properties peculiar to cells in each of its various areas.}, Author = {Horton, Jonathan C. and Adams, Daniel L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2012-07-11 13:58:24 +0000}, Issn = {0962-8436}, Journal = {Philos Trans R Soc Lond B Biol Sci}, Keywords = {research support, u.s. gov't, p.h.s. ;Visual Perception;research support, n.i.h., extramural ;21 Neurophysiology;research support, non-u.s. gov't ;Models, Neurological;Electron Transport Complex IV;Brain Mapping;Humans;Visual Pathways;Cerebral Cortex;review; mirror symmetry; retinal wave paper; Spontaneous activity; topographic map; visual system; monkey; 21 Activity-development; Neocortex}, Month = {4}, Nlm_Id = {7503623}, Number = {1456}, Organization = {Beckman Vision Center, 10 Koret Way, University of California, San Francisco, CA 94143-0730, USA.}, Pages = {837-62}, Pii = {P01XKQ6EEH9AD84T}, Pubmed = {15937015}, Title = {The cortical column: a structure without a function}, Uuid = {95DB5BDA-C3B1-4C52-8B6E-18BCB72AB084}, Volume = {360}, Year = {2005}, url = {papers/Horton_PhilosTransRSocLondBBiolSci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1098/rstb.2005.1623}} @article{Hossain:2004, Abstract = {Neonatal hypoxic-ischemic brain injury is a major cause of neurological disability and mortality. Its therapy will likely require a greater understanding of the discrete neurotoxic molecular mechanism(s) triggered by hypoxia-ischemia (HI). Here, we investigated the role of neuronal pentraxin 1 (NP1), a member of a newly recognized subfamily of "long pentraxins," in the HI injury cascade. Neonatal brains developed marked infarcts in the ipsilateral cerebral hemisphere at 24 hr and showed significant loss of ipsilateral striatal, cortical, and hippocampal volumes at 7 d after HI compared with the contralateral hemisphere and sham controls. Immunofluorescence analyses revealed elevated neuronal expression of NP1 in the ipsilateral cerebral cortex from 6 hr to 7 d and in the hippocampal CA1 and CA3 regions from 24 hr to 7 d after HI. These same brain areas developed infarcts and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-positive cells within 24-48 hr of HI. In primary cortical neurons, NP1 protein was induced >2.5-fold (p < 0.001) after their exposure to hypoxia that caused approximately 30-40\%neuronal death. Transfecting cortical neurons with antisense oligodeoxyribonucleotides directed against NP1 mRNA (NP1AS) significantly inhibited (p < 0.01) hypoxia-induced NP1 protein induction and neuronal death (p < 0.001), demonstrating a specific requirement of NP1 in hypoxic neuronal injury. NP1 protein colocalized and coimmunoprecipitated with the fast excitatory AMPA glutamate receptor subunit (GluR1) in primary cortical neurons, and hypoxia induced a time-dependent increase in NP1-GluR1 interactions. NPIAS also protected against AMPA-induced neuronal death (p < 0.05), implicating a role for NP1 in the excitotoxic cascade. Our results show that NP1 induction mediates hypoxic-ischemic injury probably by interacting with and modulating GluR1 and potentially other excitatory glutamate receptors.}, Author = {Hossain, Mir Ahamed and Russell, Juliet C. and O'Brien, Richard and Laterra, John}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {C-Reactive Protein;Dose-Response Relationship, Drug;Neurotoxins;Animals;Gene Expression Regulation;Cells, Cultured;Protein Binding;Rats;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;21 Epilepsy;Apoptosis;Cell Hypoxia;Brain;RNA, Messenger;Receptors, AMPA;Disease Models, Animal;Hypoxia-Ischemia, Brain;Animals, Newborn;Rats, Inbred F344;In Situ Nick-End Labeling;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Nerve Tissue Proteins;Oligonucleotides, Antisense;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {8102140}, Number = {17}, Organization = {Department of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. hossain\@kennedykrieger.org}, Pages = {4187-96}, Pii = {24/17/4187}, Pubmed = {15115814}, Title = {Neuronal pentraxin 1: a novel mediator of hypoxic-ischemic injury in neonatal brain}, Uuid = {22F43975-E7F2-4C86-B8D6-95CE9A5E0F9D}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0347-04.2004}} @article{Hossain-Ibrahim:2006, Abstract = {ABSTRACT: BACKGROUND: Inflammation around cell bodies of primary sensory neurons and retinal ganglion cells enhances expression of neuronal growth-associated genes and stimulates axonal regeneration. We have asked if inflammation would have similar effects on corticospinal neurons, which normally show little response to spinal cord injury. Lipopolysaccharide (LPS) was applied onto the pial surface of the motor cortex of adult rats with or without concomitant injury of the corticospinal tract at C4. Inflammation around corticospinal tract cell bodies in the motor cortex was assessed by immunohistochemistry for OX42 (a microglia and macrophage marker). Expression of growth-associated genes c-jun, ATF3, SCG10 and GAP-43 was investigated by immunohistochemistry or in situ hybridisation. RESULTS: Application of LPS-induced a gradient of inflammation through the entire depth of the motor cortex and promoted c-Jun and SCG10 expression for up to 2 weeks, and GAP-43 upregulation for 3 days by many corticospinal neurons, but had very limited effects on neuronal ATF3 expression. However, many glial cells in the subcortical white matter upregulated ATF3. LPS did not promote sprouting of anterogradely labelled corticospinal axons, which did not grow into or beyond a cervical lesion site. CONCLUSION: Inflammation produced by topical application of LPS promoted increased expression of some growth-associated genes in the cell bodies of corticospinal neurons, but was insufficient to promote regeneration of the corticospinal tract.}, Author = {Hossain-Ibrahim, and Rezajooi, and Macnally, and Mason, and Lieberman, and Anderson,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1471-2202}, Journal = {BMC Neurosci}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {100966986}, Number = {1}, Pages = {8}, Pii = {1471-2202-7-8}, Pubmed = {16433912}, Title = {Effects of lipopolysaccharide-induced inflammation on expression of growth-associated genes by corticospinal neurons}, Uuid = {41DA9E74-E89F-4076-8082-AAB65D70DEAB}, Volume = {7}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1471-2202-7-8}} @article{Houalla:2003, Abstract = {We have developed a method for isolating goldfish microglia. Cells were identified as microglia immunohistochemically with NN-2, a monoclonal antibody (MAb) raised against teleost retinal microglial cells, and by their phagocytic abilities. Morphological characterization of the cells identified round, phase-bright cells as well as flattened macrophage-like cells. Ramified cells were also seen but they were rare. Fusion of macrophage-like cells occurred in high density cultures and resulted in the formation of giant cells that disintegrated a few days later. Immunohistochemical studies demonstrated that virtually all of the cells in our cultures were NN-2+ and did not label with either antiGFAP (an astrocyte marker) or MAb 6D2 (an oligodendrocyte marker). Cells identified as microglia were intensely phagocytic and ingested latex microspheres, DiIAcLDL and goldfish myelin in vitro. In addition, we labelled microglial cells in vivo with intracranial injections of fluorescent dextran and found that microglia isolated from these animals contained the dextran and phagocytosed microspheres. We also studied the effect of myelin on microsphere uptake and compared the effect of myelin and opsonized myelin on the phagocytic activity of the cells. Our results showed a clear increase in the phagocytic activity of microglia when incubated with myelin, with an enhanced effect of opsonized myelin.}, Author = {Houalla, T. and Levine, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Research Support, Non-U.S. Gov't;Glial Fibrillary Acidic Protein;Goldfish;Immunohistochemistry;Myelin Sheath;Comparative Study;Time Factors;Cell Count;11 Glia;Microglia;Cell Culture Techniques;Microspheres;Cells, Cultured;Brain;Animals;Phagocytosis;Cell Separation}, Month = {12}, Nlm_Id = {7905558}, Number = {1-2}, Organization = {Department of Biology, McGill University, Montr{\'e}al, Qu{\'e}, Canada H3A 1B1.}, Pages = {121-31}, Pii = {S0165027003002711}, Pubmed = {14659832}, Title = {The isolation and culture of microglia-like cells from the goldfish brain}, Uuid = {014FFA6A-0663-46E1-8624-3CEBC24B8E22}, Volume = {131}, Year = {2003}, url = {papers/Houalla_JNeurosciMethods2003.pdf}} @article{Houser:1990, Abstract = {The distribution of granule cells in the dentate gyrus of the hippocampal formation was studied in control autopsy and temporal lobe epilepsy (TLE) specimens. In control tissue, the granule cell somata were closely approximated and formed a narrow lamina with a distinct, regular border with the molecular layer. In 11 of 15 TLE specimens, the granule cell somata were dispersed and formed a wider than normal granule cell layer. The granule cell somata extended into the molecular layer to varying extents, creating an irregular boundary between the lamina. The dispersed granule cells were frequently aligned in columns, and many of these neurons displayed elongated bipolar forms. The extent of granule cell dispersion appeared to be related to the amount of cell loss in the polymorph layer of the dentate gyrus. Granule cell dispersion was not consistently associated with granule cell loss although 5 of the 11 specimens with granule cell dispersion also showed moderate to marked granule cell loss. The most common features in the histories of the TLE cases with granule cell dispersion were severe febrile seizures or seizures associated with meningitis or encephalitis during the first 4 years of life. The dispersion of the granule cells suggests that there has been some alteration in the patterns of cell migration in a subpopulation of cases with severe TLE. The resultant ectopic positions of the granule cells could lead to changes in both the afferent and efferent connections of these neurons and, thus, contribute to the altered circuitry of the hippocampal formation in TLE.}, Author = {Houser, C. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Staining and Labeling;Adolescent;Adult;Epilepsy, Temporal Lobe;Female;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Risk Factors;Middle Aged;Research Support, U.S. Gov't, Non-P.H.S.;Male;Humans;Oxazines}, Medline = {91159839}, Month = {12}, Nlm_Id = {0045503}, Number = {2}, Organization = {Neurology Service, Veterans Administration Medical Center, West Los Angeles, CA.}, Pages = {195-204}, Pubmed = {1705855}, Title = {Granule cell dispersion in the dentate gyrus of humans with temporal lobe epilepsy}, Uuid = {3379D824-810D-11DA-9009-000D9346EC2A}, Volume = {535}, Year = {1990}} @article{Houser:1992, Abstract = {Multiple morphological and neurochemical changes are found in the dentate gyrus of humans with temporal lobe epilepsy (TLE). Three basically different types of changes will be discussed and some interrelationships considered. Neuronal loss in several regions of the hippocampal formation in human TLE has been recognized for many years, but only recently have the polymorph or hilar neurons been evaluated as a distinct group of neurons, and cell loss in this region is now being documented in many cases with severe TLE. Reorganization of afferents within the molecular layer of the dentate gyrus is also found in a high percentage of TLE specimens. The apparent reorganization of mossy fibers from the dentate granule cells is particularly striking, and aberrant innervation of the inner part of the molecular layer by zinc- and dynorphin-containing mossy fibers has been reported in human tissue by several groups of investigators. In a subpopulation of TLE specimens, there is also disorganization of the granule cell layer. Rather than being arranged in the compact, highly organized layer that is characteristic of control tissue, the granule cell bodies in some TLE cases are dispersed. In some additional cases, a bilaminar pattern of granule cells is observed. Each of these changes could contribute to altered circuitry within the dentate gyrus of humans with TLE, and such alterations could influence seizure susceptibility within the hippocampal formation.}, Author = {Houser, C. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0922-9833}, Journal = {Epilepsy Res Suppl}, Keywords = {Axons;Nerve Fibers;Nerve Degeneration;Nerve Regeneration;Hippocampus;Neuronal Plasticity;Research Support, U.S. Gov't, P.H.S.;Epilepsy, Temporal Lobe;Research Support, U.S. Gov't, Non-P.H.S.;Afferent Pathways;Humans;review;Neurons}, Medline = {93103514}, Nlm_Id = {8913231}, Organization = {Neurology Service, Veterans Administration Medical Center, West Los Angeles, Wadsworth Division, CA.}, Pages = {223-34}, Pubmed = {1466768}, Title = {Morphological changes in the dentate gyrus in human temporal lobe epilepsy}, Uuid = {3379DFA5-810D-11DA-9009-000D9346EC2A}, Volume = {7}, Year = {1992}} @article{Hu:2000, Abstract = {Olfactory interneuron precursors in the rostral migration stream migrate in chains and through long distances to the olfactory bulb. The migration is inhibited when polysialic acid moiety of NCAM is removed. How polysialic acid regulates chain migration has remained unknown. Previous studies in other systems have indicated the polysialic acid as a negative regulator of cell-cell interactions. Thus, polysialic acid may prevent cells in chains from interacting too tightly. To test this hypothesis and examine how polysialic acid regulates chain migration, the effect of polysialic acid depletion was evaluated in vitro and in vivo. Surprisingly, removal of polysialic acid often resulted in the dispersion of chains into single cells in both subventricular zone cultures and in adult mice where chain migration was observed. These results indicate that polysialic acid plays an important role in the formation of chains by olfactory interneuron precursors.}, Author = {Hu, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:49 -0400}, Journal = {J Neurosci Res}, Keywords = {Dose-Response Relationship, Drug;Cells, Cultured;Laminin/pharmacology;Animal;B pdf;02 Adult neurogenesis migration;Olfactory Bulb/*cytology/embryology/*metabolism;Cell Differentiation/genetics/physiology;Drug Combinations;Stem Cells/*cytology/drug effects;Proteoglycans/pharmacology;Cell Movement/drug effects/genetics/*physiology;Animals, Newborn;Mice, Inbred Strains;Support, Non-U.S. Gov't;Mice, Knockout;Sialic Acids/*metabolism/pharmacology;Neural Cell Adhesion Molecules/genetics/metabolism;Support, U.S. Gov't, P.H.S.;Interneurons/*cytology/drug effects/*metabolism;Mice;Collagen/pharmacology}, Number = {5}, Organization = {Rammelkamp Center for Education and Research, MetroHealth Medical Center, Cleveland, Ohio, USA. hhu\@research.metrohealth.org}, Pages = {480-92.}, Title = {Polysialic acid regulates chain formation by migrating olfactory interneuron precursors}, Uuid = {5655C4BF-2DA3-4303-809B-AF85874F618B}, Volume = {61}, Year = {2000}, url = {papers/Hu_JNeurosciRes2000.pdf}} @article{Hu:1996, Abstract = {During mammalian brain development, immature neurons often migrate considerable distances. A dramatic example is the rostral migration of olfactory interneuron precursors from near the septum to the olfactory bulb via a subventricular pathway. Heterotopic transplantations establish that this migration is unidirectional and that guidance cues operate over a considerable distance. The guidance cues for this translocation have not been identified, and the present studies provide evidence that a diffusible chemorepulsive factor, secreted by caudal septum but not by other tissue regions surrounding the pathway, may be involved. This activity is functionally distinct from that produced by factors that influence vertebrate axon outgrowth, such as netrin-1, netrin-2, and collapsin-1/semaphorin-III. The presence of this activity in the floor plate/ventral spinal cord as well as the septum suggests that it may influence other types of cell migration.}, Author = {Hu, H. and Rutishauser, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuron}, Keywords = {Septal Nuclei/cytology;02 Adult neurogenesis migration;Olfactory Bulb/cytology/*growth &development;Cell Communication;Rats;Cerebral Ventricles/cytology;B-5;Animal;Support, U.S. Gov't, P.H.S.;Cells, Cultured;Cell Movement;Mice;Chemotaxis;Interneurons/*cytology}, Number = {5}, Organization = {Department of Genetics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106-4955, USA.}, Pages = {933-40.}, Title = {A septum-derived chemorepulsive factor for migrating olfactory interneuron precursors}, Uuid = {E7501F31-B3D6-4E58-9E65-1C691485B60B}, Volume = {16}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8630251}} @article{Hu:1996a, Abstract = {Transplantation studies have been used to show that tangential migration of olfactory bulb interneuron precursors is retarded in NCAM- mutant mice, and that this defect reflects loss of NCAM polysialic acid (PSA). In contrast, radial migration of cells within the bulb did not require PSA. Reciprocal transplantations between wild-type and mutant mice have revealed that the mutation affects the in vivo migration environment in the subventricular zone, and not movement of individual cells. However, in vitro migration of the cells into a PSA-negative collagen matrix environment was also PSA dependent. The surprisingly similar results obtained in the in vivo and in vitro environments is consistent with the observation that migration of subventricular cells occurs as streams of closely apposed cells in which the PSA-positive cells appear to serve as their own migration substrate.}, Author = {Hu, H. and Tomasiewicz, H. and Magnuson, T. and Rutishauser, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuron}, Keywords = {Tissue Culture;Fluorescent Antibody Technique, Indirect;B abstr;Mice, Mutant Strains;Cell Movement/*physiology;Sialic Acids/genetics/*physiology;Animal;Mutation;02 Adult neurogenesis migration;Neural Cell Adhesion Molecules/chemistry/genetics;Stem Cells/*cytology;Animals, Newborn;Support, Non-U.S. Gov't;Brain/cytology;Olfactory Bulb/*cytology/transplantation;Support, U.S. Gov't, P.H.S.;Interneurons/*cytology;Mice;Collagen;Culture Media}, Number = {4}, Organization = {Department of Genetics, Case Western Reserve University, Cleveland, Ohio 44106, USA.}, Pages = {735-43.}, Title = {The role of polysialic acid in migration of olfactory bulb interneuron precursors in the subventricular zone}, Uuid = {042C2777-3C57-4CEA-AA88-88B2309B69CA}, Volume = {16}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8607992}} @article{Huang:2000, Abstract = {Our aims were to examine whether oxidative DNA damage was elevated in brain cells of male C57BL/6 mice after oxidative stress, and to determine whether neuronal nitric oxide synthase (nNOS) was involved in such damage. Oxidative stress was induced by occluding both common carotid arteries for 90 min, followed by reperfusion. Escherichia coli exonuclease III (Exo III) removes apyrimidinic or apurinic (AP) sites and 3'-phosphate termini in single-strand breaks, and converts these lesions to 3'OH termini. These ExoIII-sensitive sites (EXOSS) can then be postlabeled using digoxigenin-11-dUTP and Klenow DNA polymerase-I, and detected using fluorescein isothiocyanate-IgG against digoxigenin. Compared with the non-ischemia controls, the density of EXOSS-positive cells was elevated at least 20-fold (P <0.01) at 15 min of reperfusion, and remained elevated for another 30 min. EXOSS mainly occurred in the cell nuclei of the astrocytes and neurons. Signs of cell death were detected at 24 h of reperfusion and occurred mostly in the neurons. Both DNA damage and cell death in the cerebral cortical neurons were abolished by treatment with 3-bromo-7-nitroindazole (30 mg/kg, intraperitoneal), which specifically inhibited nNOS. Our results suggest that nNOS, its activator (calcium), and peroxynitrite exacerbate oxidative DNA damage after brain ischemia.-Huang, D., Shenoy, A., Cui, J., Huang, W., Liu, P. In situ detection of AP sites and DNA strand breaks bearing 3'-phosphate termini in ischemic mouse brain. 0892-6638 Journal Article}, Author = {Huang, D. and Shenoy, A. and Cui, J. and Huang, W. and Liu, P. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Faseb J}, Keywords = {Exodeoxyribonucleases/metabolism;Animals;Nitric-Oxide Synthase/metabolism;Reperfusion Injury/*metabolism;Arcuate Nucleus/chemistry;Cerebral Cortex/chemistry;Histocytochemistry/*methods;Astrocytes/chemistry;Mice, Inbred C57BL;08 Aberrant cell cycle;Male;EE;Support, Non-U.S. Gov't;DNA Polymerase I;In Situ Nick-End Labeling;NADP/isolation &purification;Oxidative Stress/*physiology;Support, U.S. Gov't, P.H.S.;*DNA Damage;Prosencephalon/chemistry;Brain Ischemia/*metabolism;Mice;Cell Death;Neurons/chemistry}, Number = {2}, Organization = {Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.}, Pages = {407-17}, Pubmed = {10657997}, Title = {In situ detection of AP sites and DNA strand breaks bearing 3'-phosphate termini in ischemic mouse brain}, Uuid = {DB2E6B2A-18DA-4888-8743-B1F16C7C0AE8}, Volume = {14}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10657997}} @article{Huang:2002, Abstract = {Two experiments were carried out to test whether cells which are born in adulthood and migrate to the olfactory bulb of adult male golden hamsters are activated during sexual behaviors, to determine the time course over which such responsiveness appears, and to ask whether activation is specific to sexual cues. In the first experiment, adult male hamsters were injected with 5'-bromodeoxyuridine (BrdU, 50mg/kg b.w.) 3 times over the course of one week in order to mark dividing cells. Ten days, three weeks, or seven weeks after the first BrdU injection, the animals were allowed to mate with an estrous female for half an hour before being sacrificed. Confocal analysis of fluorescent immunostaining of BrdU and c-Fos first revealed dual labeled cells in the olfactory bulb 3 weeks after injection of the thymidine analog. In order to determine whether the activation of these newly generated cells is specific to sexual cues, we next compared the incidence of c- Fos expression in newborn (BrdU positive) cells among male hamsters exposed to an estrous female, an aggressive male, a cotton swab containing vaginal secretion from an estrous female hamster (FHVS), a cotton swab containing peppermint, or a cotton swab containing distilled water. In the mitral and glomerular layers of the accessory olfactory bulb, animals exposed to an estrous female had significantly more double labeled cells than did those given other treatments (p <0.01). In the mitral layer of the main bulb, animals exposed to an estrous female had a significantly higher percentage of double labeled cells than those of other groups, except those exposed to an aggressive male (p <0.05). No double labeled cells were seen in medial preoptic area (MPOA), medial nucleus of the amygdala (Me), the bed nucleus of the stria terminalis (BNST), or the hypothalamus. Our results indicate that cells born in adulthood are more responsive to cues arising from estrous females than other stimuli, and thus may participate in sociosexual behaviors. (c) 2002 Elsevier Science (USA).}, Author = {Huang, L. and Bittman, E. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:39:49 -0400}, Journal = {Horm Behav}, Keywords = {B both;02 Adult neurogenesis migration}, Number = {3}, Organization = {Department of Biology, The University of Massachusetts, Amherst, Massachusetts, 01003}, Pages = {343-50.}, Title = {Olfactory bulb cells generated in adult male golden hamsters are specifically activated by exposure to estrous females}, Uuid = {16A33483-4D7A-4043-8422-11BF8BD31D9F}, Volume = {41}, Year = {2002}, url = {papers/Huang_HormBehav2002.pdf}} @article{Huang:1998, Abstract = {Seasonal changes in vertebrate brain function are pervasive, but annual cycles in the rates of neuronal incorporation are established only in songbirds. Although cell division continues in the subependymal and hippocampal subgranular zones of adult rodents, there exists no parallel evidence that seasonal plasticity in mammals extends to changes in neuronal or glial number. We examined the effect of photoperiod on incorporation of new neurons in the brain of the adult golden hamster, a long-day breeder. We administered the cell birth marker 5'-bromodeoxyuridine (BrdU) to males which had either been maintained in long days, transferred to short days for 10 weeks, or moved acutely from long to short or short to long days. The number of cells in specific brain regions immunoreactive (ir) for this thymidine analog was determined 7 weeks later. The number of BrdU-ir cells in the dentate gyrus and subependymal zone increased twofold in short days. Transfer between photoperiods 10 days before the BrdU injections produced intermediate numbers of BrdU-labeled cells in the dentate gyrus, but was as effective as long-term photoperiodic exposure in the subependymal zone. Photoperiod also had similar effects in the hypothalamus and cingulate/retrosplenial cortex, but not in the central gray or preoptic area. Double-label immunocytochemistry indicated that very few of the BrdU-ir cells were glia, but that a majority had neuronal phenotype. In the subependymal zone, short days significantly increased the number of BrdU-labeled neurons. We did not detect significant effects of photoperiod on the volume of either the granule cell layer of the hippocampus or the dentate gyrus as a whole. We conclude that short day lengths increase neuronal birth and/or survival in several brain regions of adult hamsters.}, Author = {Huang, L. and DeVries, G. J. and Bittman, E. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:32 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Hamsters;Animals;Photoperiod;Research Support, U.S. Gov't, Non-P.H.S.;Brain;Male;Antimetabolites;Research Support, U.S. Gov't, P.H.S.;Testis;Body Weight;Mesocricetus;Neuroglia;Dentate Gyrus;Sex Behavior, Animal;Organ Size;Neurons;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine}, Medline = {98401911}, Month = {9}, Nlm_Id = {0213640}, Number = {3}, Organization = {Department of Biology, University of Massachusetts, Amherst 01003, USA.}, Pages = {410-20}, Pii = {10.1002/(SICI)1097-4695(19980905)36:3<410::AID-NEU8>3.0.CO;2-Z}, Pubmed = {9733075}, Title = {Photoperiod regulates neuronal bromodeoxyuridine labeling in the brain of a seasonally breeding mammal}, Uuid = {FD62AB0E-5C27-4F78-ACD9-349BBE6C6AD7}, Volume = {36}, Year = {1998}} @article{Huang:2001, Abstract = {Papillary thyroid carcinoma (PTC) is clinically heterogeneous. Apart from an association with ionizing radiation, the etiology and molecular biology of PTC is poorly understood. We used oligo-based DNA arrays to study the expression profiles of eight matched pairs of normal thyroid and PTC tissues. Additional PTC tumors and other tissues were studied by reverse transcriptase-PCR and immunohistochemistry. The PTCs showed concordant expression of many genes and distinct clustered profiles. Genes with increased expression in PTC included many encoding adhesion and extracellular matrix proteins. Expression was increased in 8/8 tumors for 24 genes and in 7/8 tumors for 22 genes. Among these genes were several previously known to be overexpressed in PTC, such as MET, LGALS3, KRT19, DPP4, MDK, TIMP1, and FN1. The numerous additional genes include CITED1, CHI3L1, ODZ1, N33, SFTPB, and SCEL. Reverse transcriptase-PCR showed high expression of CITED1, CHI3L1, ODZ1, and SCEL in 6/6 additional PTCs. Immunohistochemical analysis detected CITED1 and SFTPB in 49/52 and 39/52 PTCs, respectively, but not in follicular thyroid carcinoma and normal thyroid tissue. Genes underexpressed in PTC included tumor suppressors, thyroid function-related proteins, and fatty acid binding proteins. Expression was decreased in 7/8 tumors for eight genes and decreased in 6/8 tumors for 19 genes. We conclude that, despite its clinical heterogeneity, PTC is characterized by consistent and specific molecular changes. These findings reveal clues to the molecular pathways involved in PTC and may provide biomarkers for clinical use. 0027-8424 Journal Article}, Author = {Huang, Y. and Prasad, M. and Lemon, W. J. and Hampel, H. and Wright, F. A. and Kornacker, K. and LiVolsi, V. and Frankel, W. and Kloos, R. T. and Eng, C. and Pellegata, N. S. and de la Chapelle, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Tumor Markers, Biological;*Gene Expression Profiling;Cell Adhesion Molecules/genetics;Human;Oligonucleotide Array Sequence Analysis;Reverse Transcriptase Polymerase Chain Reaction;Cluster Analysis;Thyroid Neoplasms/*genetics;Support, U.S. Gov't, P.H.S.;N;19 Neocortical evolution}, Number = {26}, Organization = {Human Cancer Genetics Program, Comprehensive Cancer Center, Department of Pathology, Divisions of Sensory Biophysics and Endocrinology and Nuclear Medicine, Ohio State University, Columbus, OH 43210, USA.}, Pages = {15044-9}, Pubmed = {11752453}, Title = {Gene expression in papillary thyroid carcinoma reveals highly consistent profiles}, Uuid = {43A9DA02-3B33-431E-A9F9-9608D842DC51}, Volume = {98}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11752453}} @article{Huard:1998, Abstract = {We have infused replication-incompetent retroviral vectors into the nasal cavity of adult rats 1 day after exposure to the olfactotoxic gas methyl bromide (MeBr) to assess the lineage relationships of cells in the regenerating olfactory epithelium. The vast majority of the retrovirus-labeled clones fall into three broad categories: clones that invariably contain globose basal cells (GBCs) and/or neurons, clones that always include cells in the ducts of Bowman's glands, and clones that are composed of sustentacular cells only. Many of the GBC-related clones contain sustentacular cells and horizontal basal cells as well. Most of the duct-related clones contain gland cells, and some also include sustentacular cells. Thus, the destruction of both neurons and non-neuronal cells that is caused by MeBr activates two distinct types of multipotent cells. The multipotent progenitor that gives rise to neurons and non-neuronal cells is a basal cell, whereas the progenitor that gives rise to duct, gland, and sustentacular cells resides within the ducts, based on the pattern of sparing after lesion and the analysis of early regeneration by using cell type-specific markers. We conclude that the balance between multipotency and selective neuropotency, which is characteristic of globose basal cells in the normal olfactory epithelium, is determined by which cell types have been depleted and need to be replenished rapidly.}, Author = {Huard, J. M. and Youngentob, S. L. and Goldstein, B. J. and Luskin, M. B. and Schwob, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {J Comp Neurol}, Keywords = {I both;Retroviridae/genetics;Genetic Vectors;Rats, Sprague-Dawley;Cell Line;Rats/*anatomy &histology;Animal;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Olfactory Mucosa/*cytology;13 Olfactory bulb anatomy;Stem Cells/*cytology}, Number = {4}, Organization = {Department of Anatomy and Cell Biology, SUNY Health Science Center, Syracuse, New York 13210, USA.}, Pages = {469-86.}, Title = {Adult olfactory epithelium contains multipotent progenitors that give rise to neurons and non-neural cells}, Uuid = {F732B3EC-67CC-4812-B3DC-82E826B3F8E6}, Volume = {400}, Year = {1998}, url = {papers/Huard_JCompNeurol1998}} @article{Huber:2006, Abstract = {Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing after wakefulness and decreasing after sleep. We showed recently that a learning task involving a circumscribed brain region produces a local increase in sleep SWA. We hypothesized that increases in cortical SWA reflect synaptic potentiation triggered by learning. To further investigate the link between synaptic plasticity and sleep, we asked whether a procedure leading to synaptic depression would cause instead a decrease in sleep SWA. We show here that if a subject's arm is immobilized during the day, motor performance deteriorates and both somatosensory and motor evoked potentials decrease over contralateral sensorimotor cortex, indicative of local synaptic depression. Notably, during subsequent sleep, SWA over the same cortical area is markedly reduced. Thus, cortical plasticity is linked to local sleep regulation without learning in the classical sense. Moreover, when synaptic strength is reduced, local sleep need is also reduced.}, Author = {Huber, Reto and Ghilardi, M. Felice and Massimini, Marcello and Ferrarelli, Fabio and Riedner, Brady A. and Peterson, Michael J. and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Restraint, Physical;Electroencephalography;research support, non-u.s. gov't;Adult;21 Neurophysiology;Arm;Neuronal Plasticity;Analysis of Variance;Psychomotor Performance;research support, n.i.h., extramural;Somatosensory Cortex;Humans;Male;Task Performance and Analysis;Sleep;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Department of Psychiatry, University of Wisconsin, Madison, Wisconsin 53719, USA.}, Pages = {1169-76}, Pii = {nn1758}, Pubmed = {16936722}, Title = {Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity}, Uuid = {0136BDAE-0AC4-4B76-AC87-CF6E29B98795}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1758}} @article{Huber:2007, Abstract = {BACKGROUND: Sleep slow wave activity (SWA) is thought to reflect sleep need, increasing in proportion to the length of prior wakefulness and decreasing during sleep. However, the process responsible for SWA regulation is not known. We showed recently that SWA increases locally after a learning task involving a circumscribed brain region, suggesting that SWA may reflect plastic changes triggered by learning. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis directly, we used transcranial magnetic stimulation (TMS) in conjunction with high-density EEG in humans. We show that 5-Hz TMS applied to motor cortex induces a localized potentiation of TMS-evoked cortical EEG responses. We then show that, in the sleep episode following 5-Hz TMS, SWA increases markedly (+39.1+/-17.4\%, p<0.01, n = 10). Electrode coregistration with magnetic resonance images localized the increase in SWA to the same premotor site as the maximum TMS-induced potentiation during wakefulness. Moreover, the magnitude of potentiation during wakefulness predicts the local increase in SWA during sleep. CONCLUSIONS/SIGNIFICANCE: These results provide direct evidence for a link between plastic changes and the local regulation of sleep need.}, Author = {Huber, Reto and Esser, Steve K. and Ferrarelli, Fabio and Massimini, Marcello and Peterson, Michael J. and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1932-6203}, Journal = {PLoS ONE}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Nlm_Id = {101285081}, Number = {3}, Organization = {Department of Psychiatry, University of Wisconsin, Madison, Madison, Wisconsin, United States of America.}, Pages = {e276}, Pubmed = {17342210}, Title = {TMS-induced cortical potentiation during wakefulness locally increases slow wave activity during sleep}, Uuid = {32D918A1-6836-4FE1-82B7-0D5F7F2B6FB2}, Volume = {2}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0000276}} @article{Huberman:2008, Abstract = {Our understanding of how mammalian sensory circuits are organized and develop has long been hindered by the lack of genetic markers of neurons with discrete functions. Here, we report a transgenic mouse selectively expressing GFP in a complete mosaic of transient OFF-alpha retinal ganglion cells (tOFF-alphaRGCs). This enabled us to relate the mosaic spacing, dendritic anatomy, and electrophysiology of these RGCs to their complete map of projections in the brain. We find that tOFF-alphaRGCs project exclusively to the superior colliculus (SC) and dorsal lateral geniculate nucleus and are restricted to a specific laminar depth within each of these targets. The axons of tOFF-alphaRGC are also organized into columns in the SC. Both laminar and columnar specificity develop through axon refinement. Disruption of cholinergic retinal waves prevents the emergence of columnar- but not laminar-specific tOFF-alphaRGC connections. Our findings reveal that in a genetically identified sensory map, spontaneous activity promotes synaptic specificity by segregating axons arising from RGCs of the same subtype.}, Author = {Huberman, Andrew D. and Manu, Mihai and Koch, Selina M. and Susman, Michael W. and Lutz, Amanda Brosius and Ullian, Erik M. and Baccus, Stephen A. and Barres, Ben A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {Retinal Ganglion Cells;Cholera Toxin;Retina;Animals;Gene Expression Regulation, Developmental;Superior Colliculi;Patch-Clamp Techniques;Visual Pathways;Axons;Mice, Transgenic;Mice, Inbred C57BL;Green Fluorescent Proteins;research support, non-u.s. gov't;Indoles;Vesicular Acetylcholine Transport Proteins;Dendrites;Animals, Newborn;Membrane Potentials;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Geniculate Bodies;Receptors, Nicotinic;Brain Mapping}, Month = {8}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Neurobiology, Fairchild Science Building D235, Stanford University School of Medicine, Palo Alto, CA 94305, USA. adh1\@stanford.edu}, Pages = {425-38}, Pii = {S0896-6273(08)00591-6}, Pubmed = {18701068}, Title = {Architecture and activity-mediated refinement of axonal projections from a mosaic of genetically identified retinal ganglion cells}, Uuid = {959422B3-549E-47D7-BE16-25E33212B9E9}, Volume = {59}, Year = {2008}, url = {papers/Huberman_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.07.018}} @article{Hudgins:1998, Abstract = {After insult or trauma, astrocytes become activated and endeavor to restore the brain's delicately balanced microenvironment. An index of their activated state is that they become enlarged or hypertrophic. Ciliary neurotrophic factor (CNTF), a member of the alpha helical family of cytokines, is synthesized by astrocytes and is generally regarded to be an autocrine and paracrine injury signal. To determine whether CNTF might be an endogenous signal that stimulates astrocyte hypertrophy in vivo, we intracerebrally injected 200 ng of recombinant human CNTF into the adult rat neocortex. To study the astrocytes their cytosol was stained with antibodies against S100beta and their nuclei were stained with propidium iodide (PI). Fluorescent images of astrocytic nuclei and somas were acquired using a confocal laser-scanning microscope and their areas were measured using the NIH image software. Within 24 h of treatment, CNTF induced a volume increase of the somas and nuclei of protoplasmic and fibrous astrocytes in vivo, and this effect persisted for at least 48 h. To determine whether CNTF activates astrocytes directly, glial cultures were treated with CNTF (10 ng/ml) and were evaluated by measuring the area of PI stained nuclei. CNTF stimulation increased the size of both polygonal and process-bearing astroglia. Since our studies in vivo have shown that CNTF induces other key aspects of gliosis (S. W. Levison et al., 1996; Exp. Neurol. 141, 256), we conclude that CNTF is a powerful activator of astrocytes and that it is likely responsible for the persistent glial hypertrophy observed following injuries and diseases of the CNS. 98197131 0014-4886 Journal Article}, Author = {Hudgins, S. N. and Levison, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Exp Neurol}, Keywords = {Human;Glial Fibrillary Acidic Protein/biosynthesis;Ciliary Neurotrophic Factor;Nerve Growth Factors/*pharmacology;Cells, Cultured;Rats;Microscopy, Confocal;Female;Animal;Rats, Sprague-Dawley;11 Glia;G abstr;Support, Non-U.S. Gov't;Neocortex/cytology/*drug effects/pathology;Nerve Tissue Proteins/*pharmacology;Cell Nucleus/drug effects/ultrastructure;Hypertrophy;Nerve Tissue Protein S 100/biosynthesis;Astrocytes/cytology/*drug effects/pathology;Recombinant Proteins/pharmacology;Cytoplasm/drug effects/ultrastructure}, Number = {2}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.}, Pages = {171-82}, Pubmed = {9527886}, Title = {Ciliary neurotrophic factor stimulates astroglial hypertrophy in vivo and in vitro}, Uuid = {CD3A96D3-A275-43A2-AF8F-72E3F22F7142}, Volume = {150}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9527886}} @article{Hudson:2004, Abstract = {Finding a reliable source of alternative neural stem cells for treatment of various diseases and injuries affecting the central nervous system is a challenge. Numerous studies have shown that hematopoietic and nonhematopoietic progenitors derived from bone marrow (BM) under specific conditions are able to differentiate into cells of all three germ layers. Recently, it was reported that cultured, unfractionated (whole) adult BM cells form nestin-positive spheres that can later initiate neural differentiation (Kabos et al., 2002). The identity of the subpopulation of BM cells that contributes to neural differentiation remains unknown. We therefore analyzed the hematopoietic and neural features of cultured, unfractionated BM cells derived from a transgenic mouse that expresses green fluorescent protein (GFP) in all tissues. We also transplanted the BM cells into the subventricular zone (SVZ), a region known to support postnatal neurogenesis. After injection of BM cells into the neurogenic SVZ in neonatal rats, we found surviving GFP+ BM cells close to the injection site and in various brain regions, including corpus callosum and subcortical white matter. Many of the grafted cells were detected within the rostral migratory stream (RMS), moving toward the olfactory bulb (OB), and some cells reached the subependymal zone of the OB. Our in vitro experiments revealed that murine GFP+ BM cells retained their proliferation and differentiation potential and predominantly preserved their hematopoietic identity (CD45, CD90, CD133), although a few expressed neural antigens (nestin, glial fibrillary acdiic protein, TuJ1).}, Author = {Hudson, J. E. and Chen, N. and Song, S. and Walczak, P. and Jendelov{\'a}, P. and Sykova, E. and Willing, A. E. and Saporta, S. and Bickford, P. and Sanchez-Ramos, J. and Zigova, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cell Survival;Pregnancy;Animals;Stem Cell Transplantation;Cells, Cultured;Rats;Comparative Study;Brain;Female;Cell Count;Rats, Sprague-Dawley;Mice, Transgenic;11 Glia;Green Fluorescent Proteins;Time Factors;Male;Hematopoiesis;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Bone Marrow Cells;Neurons;Mice;Luminescent Proteins;Immunohistochemistry;Bromodeoxyuridine;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {7600111}, Number = {2}, Organization = {Department of Neurosurgery, College of Medicine, Center of Excellence for Aging and Brain Repair, University of South Florida, Tampa, Florida 33612, USA. jhudson\@hsc.usf.edu}, Pages = {255-64}, Pubmed = {15048923}, Title = {Green fluorescent protein bone marrow cells express hematopoietic and neural antigens in culture and migrate within the neonatal rat brain}, Uuid = {89B9DB35-4D71-44A0-8C6F-598FCA312A06}, Volume = {76}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20043}} @article{Huffman:1999, Abstract = {Theories of both cortical field development and cortical evolution propose that thalamocortical projections play a critical role in the differentiation of cortical fields (; ). In the present study, we examined how changing the size of the immature neocortex before the establishment of thalamocortical connections affects the subsequent development and organization of the adult neocortex. This alteration in cortex is consistent with one of the most profound changes made to the mammalian neocortex throughout evolution: cortical size. Removing the caudal one-third to three-fourths of the cortical neuroepithelial sheet unilaterally at an early stage of development in marsupials resulted in normal spatial relationships between visual, somatosensory, and auditory cortical fields on the remaining cortical sheet. Injections of neuroanatomical tracers into the reduced cortex revealed in an altered distribution of thalamocortical axons; this alteration allowed the maintenance of their original anteroposterior distribution. These results demonstrate the capacity of the cortical neuroepithelium to accommodate different cortical fields at early stages of development, although the anteroposterior and mediolateral relationships between cortical fields appear to be invariant. The shifting of afferents and efferents with cortical reduction or expansion at very early stages of development may have occurred naturally in different lineages over time and may be sufficient to explain much of the phenotypic variation in cortical field number and organization in different mammals. 1529-2401 Journal Article}, Author = {Huffman, K. J. and Molnar, Z. and Van Dellen, A. and Kahn, D. M. and Blakemore, C. and Krubitzer, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {J Neurosci}, Keywords = {Neocortex/growth &development/*physiology;Animals;Axons/physiology;Female;Opossums/*growth &development;Species Specificity;Aging/*physiology;Male;N;Cerebral Cortex/*anatomy &histology/growth &development/*physiology;Visual Cortex/physiology;Axonal Transport;Support, Non-U.S. Gov't;19 Neocortical evolution;Somatosensory Cortex/physiology;Support, U.S. Gov't, P.H.S.;Thalamus/anatomy &histology/growth &development/*physiology;Auditory Cortex/physiology}, Number = {22}, Organization = {Center for Neuroscience and Department of Psychology, University of California, Davis, Davis, California 95616, USA.}, Pages = {9939-52}, Pubmed = {10559402}, Title = {Formation of cortical fields on a reduced cortical sheet}, Uuid = {9F8985F5-C10E-455F-BFEF-128B9CE4A705}, Volume = {19}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10559402}} @article{Huh:2000, Abstract = {Class I major histocompatibility complex (class I MHC) molecules, known to be important for immune responses to antigen, are expressed also by neurons that undergo activity-dependent, long-term structural and synaptic modifications. Here, we show that in mice genetically deficient for cell surface class I MHC or for a class I MHC receptor component, CD3zeta, refinement of connections between retina and central targets during development is incomplete. In the hippocampus of adult mutants, N-methyl-D-aspartate receptor-dependent long-term potentiation (LTP) is enhanced, and long-term depression (LTD) is absent. Specific class I MHC messenger RNAs are expressed by distinct mosaics of neurons, reflecting a potential for diverse neuronal functions. These results demonstrate an important role for these molecules in the activity-dependent remodeling and plasticity of connections in the developing and mature mammalian central nervous system (CNS).}, Author = {Huh, G. S. and Boulanger, L. M. and Du, H. and Riquelme, P. A. and Brotz, T. M. and Shatz, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Retinal Ganglion Cells;24 Pubmed search results 2008;Retina;Animals;Brain;Histocompatibility Antigens Class I;Research Support, U.S. Gov't, P.H.S.;Visual Pathways;Hippocampus;Signal Transduction;Synaptic Transmission;Synapses;Mice, Inbred C57BL;Long-Term Potentiation;Mice, Mutant Strains;Antigens, CD3;In Situ Hybridization;Neural Pathways;Neuronal Plasticity;Receptors, N-Methyl-D-Aspartate;Gene Expression Profiling;21 Activity-development;Geniculate Bodies;Mice, Knockout;21 Neurophysiology;Genes, MHC Class I;Mice;Neurons;Research Support, Non-U.S. Gov't;Receptors, GABA-A;Excitatory Postsynaptic Potentials}, Medline = {20568411}, Month = {12}, Nlm_Id = {0404511}, Number = {5499}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA. gshuh\@alum.mit.edu}, Pages = {2155-9}, Pii = {9062}, Pubmed = {11118151}, Title = {Functional requirement for class I MHC in CNS development and plasticity}, Uuid = {1E586764-38E3-426B-A38E-9454C002292F}, Volume = {290}, Year = {2000}} @article{Hull:2007, Author = {Hull, Court and Scanziani, Massimo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;21 Cortical oscillations;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {The authors are in the Section of Neurobiology, Division of Biology, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093-0634, USA. massimo\@ucsd.edu.}, Pages = {400-2}, Pii = {nn0407-400}, Pubmed = {17387326}, Title = {It's about time for thalamocortical circuits}, Uuid = {EA0AAA1E-41C5-4E40-86A4-711CE9D9968E}, Volume = {10}, Year = {2007}, url = {papers/Hull_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0407-400}} @article{Humphreys:1990, Abstract = {Brains from male cases with dyslexia show symmetry of the planum temporale and predominantly left-sided cerebrocortical microdysgenesis. We now report on three women with dyslexia. In all brains, the planum temporale was again symmetrical. Also, in two of the brains, multiple foci of cerebrocortical glial scarring were present. In both women, many of the scars were myelinated, suggesting origination during late intrauterine or early postnatal life. In one, scars were mainly left perisylvian and involved portions of the vascular border zone of the temporal cortex. In the other, scars were more numerous and occurred in the border zone of the anterior, middle, and posterior cerebral arteries symmetrically. All three cases showed to a variable extent brain warts, molecular layer ectopias, and focal architectonic dysplasia identical to those seen in the male cases. Two women had primary brain neoplasms, an oligodendroglioma and a low-grade astrocytoma, respectively, and two women showed small angiomas. Reexamination of previously reported male cases disclosed one with myelinated glial scars. Two control brains with asymmetrical plana temporale showed myelinated glial scars as well. The significance of the anatomical findings is discussed, and possible etiological factors are considered with known effects of autoimmune diseases on the nervous system.}, Author = {Humphreys, P. and Kaufmann, W. E. and Galaburda, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {24 Pubmed search results 2008;10 Development;research support, non-u.s. gov't;Adult;Aged;Aged, 80 and over;Female;Dyslexia;10 genetics malformation;comparative study;research support, u.s. gov't, p.h.s.;Humans;Brain;Male;Temporal Lobe;case reports}, Month = {12}, Nlm_Id = {7707449}, Number = {6}, Organization = {Dyslexia Research Laboratory, Charles A. Dana Research Institute, Boston, MA.}, Pages = {727-38}, Pubmed = {2285260}, Title = {Developmental dyslexia in women: neuropathological findings in three patients}, Uuid = {E2EDD918-3CD7-4F08-A8B4-E27DDE953618}, Volume = {28}, Year = {1990}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.410280602}} @article{Hurley:1999, Abstract = {Because of morphological similarities between ameboid microglia in the developing central nervous system (CNS), brain macrophages in the injured CNS, and cultured microglia in vitro, it is thought that these cell types are functionally equivalent. To investigate the validity of this assumption, we have compared mRNA levels of interleukin-1alpha and -1beta (IL-1alpha and IL-1beta), tumor necrosis factor-alpha and -beta (TNF-alpha and TNF-beta), transforming growth factor-beta1 (TGF-beta1), and macrophage colony-stimulating factor (M-CSF) in the postnatal day 4 (P4) supraventricular corpus callosum (SVCC) with those in unstimulated cultured microglia. Control tissues included spleen, cortex, hippocampus, and cerebellum. Our analyses have shown that while IL-1alpha, IL-1beta, TNF-alpha, TNF-beta, and TGF-beta1 transcripts are abundantly expressed by cultured microglia, they are very low to virtually undetectable in the SVCC. These data strongly suggest that ameboid microglia, which are concentrated in the SVCC, are unlikely to be a significant source of these cytokines. Our study, which shows clear differences in the functional status of cultured microglia vs. ameboid microglia in vivo, stresses the importance of using caution when interpreting in vitro findings in terms of the in vivo functions of microglia.}, Author = {Hurley, S. D. and Walter, S. A. and Semple-Rowland, S. L. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Macrophage Colony-Stimulating Factor;Tumor Necrosis Factor;Rats, Sprague-Dawley;Reverse Transcriptase Polymerase Chain Reaction;Hippocampus;Rats;Not relevant;Interleukin-1;Cerebellum;Gene Expression;Microglia;Support, U.S. Gov't, P.H.S.;11 Glia;Cells, Cultured;RNA, Messenger;Animals;Corpus Callosum}, Medline = {99129656}, Month = {2}, Nlm_Id = {8806785}, Number = {3}, Organization = {University of Florida Brain Institute, University of Florida, Gainesville, USA.}, Pages = {304-9}, Pii = {10.1002/(SICI)1098-1136(19990201)25:3<304::AID-GLIA10>3.0.CO;2-W}, Pubmed = {9932876}, Title = {Cytokine transcripts expressed by microglia in vitro are not expressed by ameboid microglia of the developing rat central nervous system}, Uuid = {3E52F359-8EA5-42AE-949E-38D7DD8DFEA8}, Volume = {25}, Year = {1999}, url = {papers/Hurley_Glia1999.pdf}} @article{Hurtado-Lorenzo:2006, Abstract = {The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery.}, Author = {Hurtado-Lorenzo, Andr{\'e}s and Skinner, Mhairi and El Annan, Jaafar and Futai, Masamitsu and Sun-Wada, Ge-Hong H. and Bourgoin, Sylvain and Casanova, James and Wildeman, Alan and Bechoua, Shaliha and Ausiello, Dennis A. and Brown, Dennis and Marshansky, Vladimir}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {Hydrogen-Ion Concentration;Research Support, N.I.H., Extramural;Cell Line;GTPase-Activating Proteins;Epithelial Cells;Green Fluorescent Proteins;24 Pubmed search results 2008;Kidney Tubules, Proximal;Endocytosis;Animals;Dynamins;Protein Interaction Mapping;Proteins;Isoenzymes;Transfection;Hela Cells;Vacuolar Proton-Translocating ATPases;Serum Albumin, Bovine;Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone;11 Glia;Mutation;Protein Binding;Protein Transport;ADP-Ribosylation Factors;Mice;Models, Biological;Macrolides;Humans;Endosomes;Research Support, Non-U.S. Gov't;Ammonium Chloride}, Month = {2}, Nlm_Id = {100890575}, Number = {2}, Organization = {Program in Membrane Biology & Nephrology Division, Richard Simches Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA.}, Pages = {124-36}, Pii = {ncb1348}, Pubmed = {16415858}, Title = {V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway}, Uuid = {0F1B1181-3D9B-4C44-BF32-C890A10178F0}, Volume = {8}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb1348}} @article{Hutchings:1986, Abstract = {Using scanning and transmission electron microscopy and light microscopy, the authors studied the human pia mater and its relationship to the entry of blood vessels into the normal cerebral cortex. The purpose of this investigation was to examine the long-established concept that the subarachnoid space communicates directly with the perivascular spaces of the cerebral cortex. Brains obtained post mortem from subjects with recent subarachnoid hemorrhage (SAH) and purulent leptomeningitis were studied by light microscopy to determine the permeability of the pia mater to red blood cells and inflammatory cells. Scanning electron microscopy showed that the normal pia mater is a flat sheet of cells that is reflected from the surface of the brain to form the outer coating of the meningeal vessels in the subarachnoid space. Transmission electron microscopy confirmed that the cells of the pia mater are joined by junctional complexes and form a continuous sheet that separates the subarachnoid space on one side from the subpial and perivascular spaces on the other. Thus, neither the pia mater nor the subarachnoid space extends into the brain beside blood vessels as they enter the cerebral cortex. The perivascular spaces were, in fact, found to be confluent with the subpial space and not with the subarachnoid space. In cases of recent SAH, red blood cells did not enter the perivascular spaces from the subarachnoid space; neither did India ink injected post mortem into the subarachnoid space pass into the perivascular spaces. The results of these crude tracer studies suggest that the pia mater is an effective barrier to the passage of particulate matter. Histological examination of brains of patients who had died with purulent leptomeningitis showed that inflammatory cells were present in the cortical perivascular spaces and in the contiguous subpial spaces. The presence of a large number of inflammatory cells in the subarachnoid space suggests that inflammatory cells readily penetrate the pia mater that separates the perivascular spaces from the subarachnoid space. The permeability of the pia mater to small molecular weight substances is briefly discussed.}, Author = {Hutchings, M. and Weller, R. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0022-3085}, Journal = {J Neurosurg}, Keywords = {Meningitis;Research Support, Non-U.S. Gov't;Aged;Adult;Microscopy, Electron, Scanning;Pia Mater;Middle Aged;11 Glia;Humans;Brain;Subarachnoid Hemorrhage}, Medline = {86280693}, Month = {9}, Nlm_Id = {0253357}, Number = {3}, Pages = {316-25}, Pubmed = {3734882}, Title = {Anatomical relationships of the pia mater to cerebral blood vessels in man}, Uuid = {FBDD127C-146E-49C2-9734-AD5B5492BE01}, Volume = {65}, Year = {1986}} @article{Huttmann:2003, Abstract = {Kainate-induced seizures increase hippocampal neurogenesis. Glial fibrillary acidic protein-positive astrocytes with radial processes in the dentate gyrus share many of the characteristics of radial glia and appear to act as precursor cells for adult dentate neurogenesis. Using the chemoconvulsant kainate and transgenic mice with human glial-fibrillary acidic protein (hGFAP) promoter-controlled enhanced green fluorescent protein (EGFP) expression, we examined the proliferation, morphology and electrophysiological properties of astrocytes in the neurogenic subgranular zone of the dentate gyrus in control animals and upon the induction of seizure-induced cell proliferation, three days post-kainate. EGFP-positive cells with and without radial processes could easily be distinguished. Kainate treatment caused a significant increase in the total number of proliferating EGFP-positive cells, particularly a tenfold elevation in the number of proliferating radial glia-like astrocytes, and also caused a preferential shift in the dividing cell population towards cells expressing EGFP. Immunohistochemical analysis revealed a surprisingly low proportion of cells coexpressing the astroglial marker S100beta and EGFP. Kainate increased the number of EGFP-positive, S100beta-positive and S100beta-positive-EGFP-positive astrocytes in the subgranular zone. We also report a subset of faintly EGFP-positive cells expressing markers of early neuronal differentiation. Patch-clamp analysis revealed the presence of three functionally different populations of EGFP-positive cells in both kainate and control tissue. We conclude that there is an early increase in proliferating radial glia-like astrocytes in the dentate after kainate-induced seizures, consistent with a recruitment of precursors for seizure-induced neurogenesis. 0953-816x Journal Article}, Author = {Huttmann, K. and Sadgrove, M. and Wallraff, A. and Hinterkeuser, S. and Kirchhoff, F. and Steinhauser, C. and Gray, W. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Eur J Neurosci}, Keywords = {Human;Microscopy, Confocal/methods;Animals;Membrane Potentials/physiology;In Vitro;*Cell Differentiation;Comparative Study;Phenotype;Neural Cell Adhesion Molecule L1/metabolism;Immunohistochemistry/methods;Cell Count;D pdf;Mice, Transgenic;Kainic Acid;Bromodeoxyuridine/metabolism;Animals, Newborn;Support, Non-U.S. Gov't;Astrocytes/*physiology;Sialic Acids/metabolism;S100 Proteins/metabolism;06 Adult neurogenesis injury induced;Dentate Gyrus/*pathology;Nerve Tissue Proteins/metabolism;Mice;Luminescent Proteins/genetics/metabolism;Neurons/physiology;Seizures/chemically induced/*pathology;Patch-Clamp Techniques/methods;Glial Fibrillary Acidic Protein/genetics/*metabolism}, Number = {10}, Organization = {Experimental Neurobiology, Neurosurgery, University of Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.}, Pages = {2769-78}, Pubmed = {14656326}, Title = {Seizures preferentially stimulate proliferation of radial glia-like astrocytes in the adult dentate gyrus: functional and immunocytochemical analysis}, Uuid = {38BE8F9C-8731-453B-8F38-9E8E2A160AA5}, Volume = {18}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14656326}} @article{Hwang:1999, Abstract = {In human cells, efficient global genomic repair of DNA damage induced by ultraviolet radiation requires the p53 tumor suppressor, but the mechanism has been unclear. The p48 gene is required for expression of an ultraviolet radiation-damaged DNA binding activity and is disrupted by mutations in the subset of xeroderma pigmentosum group E cells that lack this activity. Here, we show that p48 mRNA levels strongly depend on basal p53 expression and increase further after DNA damage in a p53-dependent manner. Furthermore, like p53(-/-) cells, xeroderma pigmentosum group E cells are deficient in global genomic repair. These results identify p48 as the link between p53 and the nucleotide excision repair apparatus. 0027-8424 Journal Article}, Author = {Hwang, B. J. and Ford, J. M. and Hanawalt, P. C. and Chu, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Protein p53/*genetics;Genes, Structural, Neoplasm/*genetics;Ultraviolet Rays;Gene Expression Regulation, Neoplastic/*genetics;DNA Repair/*genetics;Human;Xeroderma Pigmentosum/*genetics;08 Aberrant cell cycle;Support, U.S. Gov't, Non-P.H.S.;DNA Damage/genetics;Support, U.S. Gov't, P.H.S.;DNA-Binding Proteins/*genetics;Support, Non-U.S. Gov't;Fibroblasts;RNA, Messenger/genetics;Radiation, Ionizing;EE}, Number = {2}, Organization = {Departments of Medicine and Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5115, USA.}, Pages = {424-8}, Pubmed = {9892649}, Title = {Expression of the p48 xeroderma pigmentosum gene is p53-dependent and is involved in global genomic repair}, Uuid = {60D4D9DE-F438-4866-8F21-AB0A3F59BBE8}, Volume = {96}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9892649}} @article{Hynes:2000, Author = {Hynes, M. and Rosenthal, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Neuron}, Keywords = {Neurons/cytology/metabolism;Parkinson Disease/*therapy;Dopamine/*metabolism;17 Transplant Regeneration;Cell Differentiation/*physiology;Human;Growth Substances/metabolism/pharmacology;L;Aging/physiology;Animal;Stem Cells/cytology/*metabolism/*transplantation;Bone Morphogenetic Proteins/metabolism;Cell Lineage}, Number = {1}, Organization = {Renovis, Inc, Oakland, California 94609, USA. mhynes\@concentric.net}, Pages = {11-4.}, Title = {Embryonic stem cells go dopaminergic}, Uuid = {0C725360-55E8-4651-9B8D-6C544C0833D1}, Volume = {28}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11086977}} @article{Iannetti:2001, Abstract = {Band heterotopias are an example of genetic generalized neuronal migration disorders that may be present in patients with mild epilepsy and normal or slightly impaired intellect, as well as in patients with intractable epilepsy and mental retardation. The case of a 17-year-old left-handed female patient with epilepsy and normal cognitive development is reported in whom single-photon emission computed tomography (SPECT), proton magnetic resonance spectroscopy, and functional magnetic resonance imaging (fMRI) were performed. MRI revealed the presence of bilateral asymmetric band heterotopia. SPECT revealed a left frontoparietal and occipital hypoperfusion, demonstrating a good correlation with the electroencephalogram abnormalities. Because of the appearance of new types of seizures, the patient underwent a second MRI investigation together with a proton magnetic resonance spectroscopy (MRS) study. MRI confirmed bilateral band heterotopia characterized by greater thickness in the left hemisphere at the frontal and occipital level. MRI and SPECT findings were in agreement with left occipital electroencephalogram abnormalities and with occipital seizure type. Qualitative results of proton MRS revealed normal spectra profiles in the examined left frontal and occipital heterotopic area and in the normal overlying cortex. Later, fMRI was performed. The finger-tapping test of the right hand yielded the activation of both normal left sensory-motor cortex and the facing band heterotopia. In the right hemisphere, only the activation of the sensory-motor neocortex was observed; no involvement of the right misplaced brain tissue was present. This functional behavior could be considered the consequence of poor neuronal representation. On the contrary, the involvement of both band heterotopia and normal cortex observed in the left hemisphere could be the result of many synaptic interconnections. Functional investigations may have an important role in defining the activity of band heterotopia per se and in relation to the overlying neocortex.}, Author = {Iannetti, P. and Spalice, A. and Raucci, U. and Perla, F. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0887-8994}, Journal = {Pediatr Neurol}, Keywords = {case reports;Magnetic Resonance Imaging;Radiopharmaceuticals;Humans;Dominance, Cerebral;Tomography, Emission-Computed, Single-Photon;Brain;21 Epilepsy;Female;Epilepsy;Cell Movement;Brain Diseases;Intelligence;Mutation, Missense;21 Neurophysiology;24 Pubmed search results 2008;Technetium Tc 99m Exametazime;Choristoma;Adolescent}, Medline = {21172232}, Month = {2}, Nlm_Id = {8508183}, Number = {2}, Organization = {Division of Pediatric Neurology, Pediatrics Department, "La Sapienza" University, Roma, Italy.}, Pages = {159-63}, Pii = {S0887899400002472}, Pubmed = {11275469}, Title = {Functional neuroradiologic investigations in band heterotopia}, Uuid = {C5655C1B-01E1-4F8E-8C68-52C5407F6D39}, Volume = {24}, Year = {2001}} @article{Ikegami:2002, Abstract = {Transdifferentiation from retinal pigment epithelium (RPE) to neural retina (NR) was studied under a new culture system as an experimental model for newt retinal regeneration. Adult newt RPEs were organ cultured with surrounding connective tissues, such as the choroid and sclera, on a filter membrane. Around day 7 in vitro, lightly pigmented "neuron-like cells" with neuritic processes were found migrating out from the explant onto the filter membrane. Their number gradually increased day by day. BrdU-labeling study showed that RPE cells initiated to proliferate under the culture condition on day 4 in vitro, temporally correlating to the time course of retinal regeneration in vivo. Histological observations of cultured explants showed that proliferating RPE cells did not form the stratified structure typically observed in the NR but they rather migrated out from the explants. Neuronal differentiation was examined by immunohistochemical detection of various neuron-specific proteins; HPC-1 (syntaxin), GABA, serotonin, rhodopsin, and acetylated tubulin. Immunoreactive cells for these proteins always possessed fine and long neurite-like processes. Numerous lightly pigmented cells with neuron-like morphology showed HPC-1 immunoreactivity. Fibroblast growth factor-2 (FGF-2), known as a potent factor for the transdifferentiation of ocular tissues in various vertebrates, substantially increased the numbers of both neuron-like cells and HPC-1-like immunoreactive cells in a dose-dependent manner. These results indicate that our culture method ensures neural differentiation of newt RPE cells in vitro and provides, for the first time, a suitable in vitro experimental model system for studying tissue-intrinsic factors responsible for newt retinal regeneration.}, Author = {Ikegami, Yoko and Mitsuda, Sanae and Araki, Masasuke}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Cell Differentiation;Research Support, Non-U.S. Gov't;Pigment Epithelium of Eye;Nerve Regeneration;Immunohistochemistry;Salamandridae;Connective Tissue;Epithelial Cells;Female;Microscopy, Phase-Contrast;Cell Division;Organ Culture Techniques;Antimetabolites;Cells, Cultured;24 Pubmed search results 2008;Bromodeoxyuridine;Animals}, Medline = {21668592}, Month = {2}, Nlm_Id = {0213640}, Number = {3}, Organization = {Developmental Neurobiology Laboratory, Department of Biological Sciences, Faculty of Science, Nara Women's University, Nara 630-8506, Japan.}, Pages = {209-20}, Pii = {10.1002/neu.10031}, Pubmed = {11810636}, Title = {Neural cell differentiation from retinal pigment epithelial cells of the newt: an organ culture model for the urodele retinal regeneration}, Uuid = {04FD1661-131B-4164-BD98-A49F79C17B42}, Volume = {50}, Year = {2002}} @article{Ikegaya:2005, Abstract = {Bulk loading of calcium indicators has provided a unique opportunity to reconstruct the activity of cortical networks with single-cell resolution. Here we describe the detailed methods of bulk loading of AM dyes we developed and have been improving for imaging with a spinning disk confocal microscope.}, Author = {Ikegaya, Yuji and Le Bon-Jego, Morgane and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Microscopy, Confocal;Imaging, Three-Dimensional;Research Support, Non-U.S. Gov't;Neuroglia;21 Neurophysiology;Image Processing, Computer-Assisted;21 Calcium imaging;Fluorescent Dyes;Calcium;Animals;Mice;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {8500749}, Number = {2}, Organization = {Department of Biological Sciences, Columbia University, 1002 Fairchild Center, M.C. 2435 New York, NY 10027, USA. ikegaya\@tk.air.jp}, Pages = {132-8}, Pii = {S0168-0102(05)00063-5}, Pubmed = {15893573}, Title = {Large-scale imaging of cortical network activity with calcium indicators}, Uuid = {95609A84-99BE-4B62-BFAD-EC099DAAE61F}, Volume = {52}, Year = {2005}, url = {papers/Ikegaya_NeurosciRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neures.2005.02.004}} @article{Ikegaya:2004, Abstract = {How can neural activity propagate through cortical networks built with weak, stochastic synapses? We find precise repetitions of spontaneous patterns of synaptic inputs in neocortical neurons in vivo and in vitro. These patterns repeat after minutes, maintaining millisecond accuracy. Calcium imaging of slices reveals reactivation of sequences of cells during the occurrence of repeated intracellular synaptic patterns. The spontaneous activity drifts with time, engaging different cells. Sequences of active neurons have distinct spatial structures and are repeated in the same order over tens of seconds, revealing modular temporal dynamics. Higher order sequences are replayed with compressed timing.}, Author = {Ikegaya, Yuji and Aaron, Gloster and Cossart, Rosa and Aronov, Dmitriy and Lampl, Ilan and Ferster, David and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Excitatory Postsynaptic Potentials;Animals;Prefrontal Cortex;Synapses;In Vitro;Microscopy, Confocal;Synaptic Transmission;Patch-Clamp Techniques;2-Amino-5-phosphonovalerate;Pyramidal Cells;Mice, Inbred C57BL;Calcium;Time Factors;21 Calcium imaging;Nerve Net;Action Potentials;(R)-2,3,4,5-Tetrahydro-8-chloro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Receptors, Dopamine D1;Neurons;2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine;Mice;21 Cortical oscillations;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Cats;Visual Cortex;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {0404511}, Number = {5670}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {559-64}, Pii = {304/5670/559}, Pubmed = {15105494}, Title = {Synfire chains and cortical songs: temporal modules of cortical activity}, Uuid = {9FBD1E33-A51D-446F-BCF8-7CB15E33829A}, Volume = {304}, Year = {2004}, url = {papers/Ikegaya_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1093173}} @article{Ikonomidou:1999, Abstract = {Programmed cell death (apoptosis) occurs during normal development of the central nervous system. However, the mechanisms that determine which neurons will succumb to apoptosis are poorly understood. Blockade of N-methyl-D-aspartate (NMDA) glutamate receptors for only a few hours during late fetal or early neonatal life triggered widespread apoptotic neurodegeneration in the developing rat brain, suggesting that the excitatory neurotransmitter glutamate, acting at NMDA receptors, controls neuronal survival. These findings may have relevance to human neurodevelopmental disorders involving prenatal (drug-abusing mothers) or postnatal (pediatric anesthesia) exposure to drugs that block NMDA receptors.}, Author = {Ikonomidou, C. and Bosch, F. and Miksa, M. and Bittigau, P. and Vockler, J. and Dikranian, K. and Tenkova, T. I. and Stefovska, V. and Turski, L. and Olney, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:54 -0400}, Journal = {Science}, Keywords = {Fetus;Quinoxalines/pharmacology;*Nerve Degeneration;Dopamine Antagonists/pharmacology;Dose-Response Relationship, Drug;Dizocilpine Maleate/pharmacology;Rats;Muscarinic Antagonists/pharmacology;Excitatory Amino Acid Antagonists/pharmacology;07 Excitotoxicity Apoptosis;Receptors, N-Methyl-D-Aspartate/*antagonists &inhibitors/metabolism;Animal;E-9;Calcium Channel Blockers/pharmacology;Haloperidol/pharmacology;Support, Non-U.S. Gov't;Neurons/*cytology/drug effects/metabolism;In Situ Nick-End Labeling;*Apoptosis;Scopolamine/pharmacology;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Microscopy, Electron;Brain/*cytology/drug effects/embryology/growth &development}, Number = {5398}, Organization = {Department of Pediatric Neurology, Charite-Virchow Clinics, Humboldt University, Augustenburger Platz 1, 13353 Berlin, Germany. hrissanthi.ikonomidou\@charite.de}, Pages = {70-4.}, Title = {Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain}, Uuid = {6AE9BA62-8306-4883-AF20-A7B98EF4ED9B}, Volume = {283}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9872743}} @article{Illes:2007, Abstract = {Embryonic stem cells can be differentiated into neurons of diverse neurotransmitter-specific phenotypes. While the time course of functional progression of ES cell-derived neural precursors towards mature neurons has been described in detail on single-cell level, the temporal development and pharmacological modulation of ES cell-derived neuronal network activity have not been explored yet. Neuronal network activity can be assessed by the microelectrode array (MEA) technology that allows simultaneous monitoring of the electrical activity exhibited by entire populations of neurons over several weeks or months in vitro. We demonstrate here that ES cell-derived neural precursors cultured on MEAs for 5 to 6 weeks develop neuronal networks with oscillating and synchronous spike patterns via distinct states of activity and change electrophysiological characteristics even after 5 to 6 weeks in culture pointing towards late maturational processes. These processes were accompanied by an increasing density of presynaptic vesicles. Furthermore, we demonstrated that ES cell-derived network activity was sensitive to synaptically acting drugs indicating that pharmacologically susceptible neuronal networks were generated. Thus, the MEA technology represents a powerful tool to describe the temporal progression of stem cell-derived neural populations towards mature, functioning neuronal networks that can be applied to investigate pharmacologically active compounds.}, Author = {Illes, Sebastian and Fleischer, Wiebke and Siebler, Mario and Hartung, Hans-Peter P. and Dihn{\'e}, Marcel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {gamma-Aminobutyric Acid;Cell Differentiation;Electrophysiology;Animals;Synaptic Vesicles;Tetrodotoxin;research support, non-u.s. gov't;Time Factors;Cell Line;Embryonic Stem Cells;Action Potentials;Nerve Net;N-Methylaspartate;21 Neurophysiology;Neurons;GABA Antagonists;Microelectrodes;24 Pubmed search results 2008;Immunohistochemistry;Oscillometry}, Month = {9}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Neurology, University Hospital D{\"u}sseldorf, Heinrich-Heine University, Germany.}, Pages = {171-6}, Pii = {S0014-4886(07)00218-X}, Pubmed = {17644089}, Title = {Development and pharmacological modulation of embryonic stem cell-derived neuronal network activity}, Uuid = {05103017-A86E-4860-98E2-CF07433393D3}, Volume = {207}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2007.05.020}} @article{Imasawa:2001, Abstract = {Bone marrow stem cells (BMC) develop into hematopoietic and mesenchymal lineages but have not been known to differentiate into glomerular cells. To investigate whether such differentiation is possible, a search was made for donor glomerular cells in lethally irradiated C57BL/6j (B6) mice given transplants of BMC from syngeneic mice transgenic for green fluorescence protein (GFP) ([GFP-->B6] mice). After the recipients of donor BMC manifested GFP-positive cells in their glomeruli, the numbers of such cells increased markedly, in a time-dependent manner, from 2 wk to 24 wk after bone marrow transplantation. Immunohistochemical analyses revealed that most GFP-positive cells in the glomeruli were neither macrophages nor T cells. With the use of a laser-scanning confocal microscope, GFP-positive cells were observed within the mesangium of [GFP-->B6] mice. Furthermore, indirect immunofluorescence assays demonstrated that desmin-positive cells in the glomeruli of these chimeric mice were also positive for GFP. Among glomerular cells isolated from [GFP-->B6] mice 24 wk after bone marrow transplantation and then cultured, the majority of cells (approximately 84\%) stained for desmin and approximately 60\%of the desmin-positive cells expressed GFP. In addition, these GFP-positive cells in the cultures contracted in response to angiotensin II stimulation. These results suggest that bone marrow-derived cells may have the potential to differentiate into glomerular mesangial cells.}, Author = {Imasawa, T. and Utsunomiya, Y. and Kawamura, T. and Zhong, Y. and Nagasawa, R. and Okabe, M. and Maruyama, N. and Hosoya, T. and Ohno, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {1046-6673}, Journal = {J Am Soc Nephrol}, Keywords = {Cell Differentiation;Glomerular Mesangium;Animals;Cells, Cultured;Bone Marrow Transplantation;Female;Indicators and Reagents;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Time Factors;Angiotensin II;Bone Marrow Cells;Tissue Donors;Desmin;Mice;Luminescent Proteins}, Medline = {21316373}, Month = {7}, Nlm_Id = {9013836}, Number = {7}, Organization = {Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. imasawa\@nifty.com}, Pages = {1401-9}, Pubmed = {11423569}, Title = {The potential of bone marrow-derived cells to differentiate to glomerular mesangial cells}, Uuid = {5EF0F651-7ABB-4CF8-A707-5012B0795D6A}, Volume = {12}, Year = {2001}} @article{Imitola:2004, Abstract = {Migration toward pathology is the first critical step in stem cell engagement during regeneration. Neural stem cells (NSCs) migrate through the parenchyma along nonstereotypical routes in a precise directed manner across great distances to injury sites in the CNS, where they might engage niches harboring local transiently expressed reparative signals. The molecular mechanisms for NSC mobilization have not been identified. Because NSCs seem to home similarly to pathologic sites derived from disparate etiologies, we hypothesized that the inflammatory response itself, a characteristic common to all, guides the behavior of potentially reparative cells. As proof of concept, we show that human NSCs migrate in vivo (including from the contralateral hemisphere) toward an infarcted area (a representative CNS injury), where local astrocytes and endothelium up-regulate the inflammatory chemoattractant stromal cell-derived factor 1alpha (SDF-1alpha). NSCs express CXC chemokine receptor 4 (CXCR4), the cognate receptor for SDF-1alpha. Exposure of SDF-1alpha to quiescent NSCs enhances proliferation, promotes chain migration and transmigration, and activates intracellular molecular pathways mediating engagement. CXCR4 blockade abrogates their pathology-directed chain migration, a developmentally relevant mode of tangential migration that, if recapitulated, could explain homing along nonstereotypical paths. Our data implicate SDF-1alpha/CXCR4, representative of the inflammatory milieu characterizing many pathologies, as a pathway that activates NSC molecular programs during injury and suggest that inflammation may be viewed not simply as playing an adverse role but also as providing stimuli that recruit cells with a regenerative homeostasis-promoting capacity. CXCR4 expression within germinal zones suggests that NSC homing after injury and migration during development may invoke similar mechanisms.}, Author = {Imitola, Jaime and Raddassi, Khadir and Park, Kook In and Mueller, Franz-Josef J. and Nieto, Marta and Teng, Yang D. and Frenkel, Dan and Li, Jianxue and Sidman, Richard L. and Walsh, Christopher A. and Snyder, Evan Y. and Khoury, Samia J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Receptors, CXCR4;Ischemia;Dose-Response Relationship, Drug;Animals;Stem Cell Transplantation;Humans;Up-Regulation;Neural Crest;Brain;Models, Statistical;Cell Movement;02 Adult neurogenesis migration;Anoxia;Cell Proliferation;Fibroblast Growth Factor 2;17 Transplant Regeneration;11 Glia;Cell Line;Microscopy, Fluorescence;Research Support, U.S. Gov't, P.H.S.;Mice;24 Pubmed search results 2008;Central Nervous System;Stem Cells;Inflammation;Research Support, Non-U.S. Gov't}, Month = {12}, Nlm_Id = {7505876}, Number = {52}, Organization = {Center for Neurologic Diseases, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {18117-22}, Pii = {0408258102}, Pubmed = {15608062}, Title = {Directed migration of neural stem cells to sites of CNS injury by the stromal cell-derived factor 1alpha/CXC chemokine receptor 4 pathway}, Uuid = {23FB1259-216C-49B6-9D9F-85C499CACA85}, Volume = {101}, Year = {2004}, url = {papers/Imitola_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0408258102}} @article{Imura:2003, Abstract = {Periventricular germinal zones (GZs) of developing and adult brain contain neural stem cells (NSCs), the cellular identities and origins of which are not defined completely. We used tissue culture techniques and transgenic mice expressing herpes simplex virus thymidine kinase (HSV-TK) from the mouse glial fibrillary acid protein (GFAP) promoter to test the hypothesis that certain NSCs express GFAP. To do so, we determined the relative proportions of multipotent neurospheres that are formed by GFAP-expressing cells derived from GZs at different stages of development. In this transgenic model, dividing GFAP-expressing cells are ablated selectively by treatment with the antiviral agent ganciclovir (GCV). Single-cell analysis showed that transgene-derived HSV-TK was present only in GFAP-expressing cells. GCV applied in vitro eliminated growth of multipotent neurospheres from GZs of postnatal and adult transgenic mice but not early embryonic (embryonic day 12.5) transgenic mice. GCV prevented growth of secondary multipotent neurospheres prepared after passage of primary transgenic neurospheres derived from all three of these developmental stages. In addition, GCV prevented growth of multipotent neurospheres from transgenic astrocyte-enriched cell cultures derived from postnatal GZ, and elaidic acid GCV given for 4 d to adult transgenic mice in vivo abolished the ability to grow multipotent neurospheres from GZ. Extensive control experiments, including clonal analysis, demonstrated that failure of neurosphere growth was not merely secondary to loss of GFAP-expressing support cells or the result of a nonspecific toxic effect. Our findings demonstrate that the predominant multipotent NSCs isolated from postnatal and adult but not early embryonic GZs express GFAP, and that NSCs exhibit heterogeneous expression of intermediate filaments during developmental maturation. 1529-2401 Journal Article}, Author = {Imura, T. and Kornblum, H. I. and Sofroniew, M. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {J Neurosci}, Keywords = {Stem Cells/cytology/*metabolism/physiology;Intermediate Filament Proteins/metabolism;02 Adult neurogenesis migration;Astrocytes/physiology;Support, Non-U.S. Gov't;BB pdf;03 Adult neurogenesis progenitor source;Prosencephalon/*cytology/embryology/*growth &development/metabolism;Neurons/*cytology;Mice, Transgenic;Support, U.S. Gov't, P.H.S.;Thymidine Kinase/genetics;Mice;Animals;Ganciclovir/pharmacology;Glial Fibrillary Acidic Protein/genetics/*metabolism;Cells, Cultured}, Number = {7}, Organization = {Department of Neurobiology, Brain Research Institute, University of California, Los Angeles, California 90095-1763, USA.}, Pages = {2824-32}, Pubmed = {12684469}, Title = {The predominant neural stem cell isolated from postnatal and adult forebrain but not early embryonic forebrain expresses GFAP}, Uuid = {7710F75A-68D7-11DA-A4B6-000D9346EC2A}, Volume = {23}, Year = {2003}, url = {papers/Imura_JNeurosci2003.pdf}} @article{Inan:2006, Abstract = {The cellular and molecular mechanisms mediating the activity-dependent development of brain circuitry are still incompletely understood. Here, we examine the role of cAMP-dependent protein kinase [protein kinase A (PKA)] signaling in cortical development and plasticity, focusing on its role in thalamocortical synapse and barrel map development. We provide direct evidence that PKA activity mediates barrel map formation using knock-out mice that lack type IIbeta regulatory subunits of PKA (PKARIIbeta). We show that PKARIIbeta-mediated PKA function is required for proper dendritogenesis and the organization of cortical layer IV neurons into barrels, but not for the development and plasticity of thalamocortical afferent clustering into a barrel pattern. We localize PKARIIbeta function to postsynaptic processes in barrel cortex and show that postsynaptic PKA targets, but not presynaptic PKA targets, have decreased phosphorylation in pkar2b knock-out (PKARIIbeta(-/-)) mice. We also show that long-term potentiation at TC synapses and the associated developmental increase in AMPA receptor function at these synapses, which normally occurs as barrels form, is absent in PKARIIbeta(-/-) mice. Together, these experiments support an activity-dependent model for barrel map development in which the selective addition and elimination of thalamocortical synapses based on Hebbian mechanisms for synapse formation is mediated by a cAMP/PKA-dependent pathway that relies on PKARIIbeta function.}, Author = {Inan, Melis and Lu, Hui-Chen C. and Albright, Michael J. and She, Wei-Chi C. and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Thalamus;Cyclic AMP-Dependent Protein Kinases;research support, non-u.s. gov't;Cyclic AMP;Mice, Knockout;Neuronal Plasticity;Mice, Inbred C57BL;Signal Transduction;Protein Subunits;comparative study;research support, n.i.h., extramural;Animals, Newborn;Animals;Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit;24 Pubmed search results 2008;Cerebral Cortex;Mice}, Month = {4}, Nlm_Id = {8102140}, Number = {16}, Organization = {Division of Neurology/Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.}, Pages = {4338-49}, Pii = {26/16/4338}, Pubmed = {16624954}, Title = {Barrel map development relies on protein kinase A regulatory subunit II beta-mediated cAMP signaling}, Uuid = {D13B1B4B-AA5C-4A6E-89C0-A40960D0FAC3}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3745-05.2006}} @article{Inan:2007, Abstract = {One approach to examining how higher sensory, motor, and cognitive faculties emerge in the neocortex is to elucidate the underlying wiring principles of the brain during development. The mammalian neocortex is a layered structure generated from a sheet of proliferating ventricular cells that progressively divide to form specific functional areas, such as the primary somatosensory (S1) and motor (M1) cortices. The basic wiring pattern in each of these functional areas is based on a similar framework, but is distinct in detail. Functional specialization in each area derives from a combination of molecular cues within the cortex and neuronal activity-dependent cues provided by innervating axons from the thalamus. One salient feature of neocortical development is the establishment of topographic maps in which neighboring neurons receive input relayed from neighboring sensory afferents. Barrels, which are prominent sensory units in the somatosensory cortex of rodents, have been examined in detail, and data suggest that the initial, gross formation of the barrel map relies on molecular cues, but the refinement of this topography depends on neuronal activity. Several excellent reviews have been published on the patterning and plasticity of the barrel cortex and the precise targeting of ventrobasal thalamic axons. In this review, the authors will focus on the formation and functional maturation of synapses between thalamocortical axons and cortical neurons, an event that coincides with the formation of the barrel map. They will briefly review cortical patterning and the initial targeting of thalamic axons, with an emphasis on recent findings. The rest of the review will be devoted to summarizing their understanding of the cellular and molecular mechanisms underlying thalamocortical synapse maturation and its role in barrel map formation.}, Author = {Inan, Melis and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1073-8584}, Journal = {Neuroscientist}, Keywords = {Receptors, Glutamate;Synaptic Membranes;Gene Expression Regulation, Developmental;Ventral Thalamic Nuclei;Rats;Neural Pathways;Signal Transduction;research support, n.i.h., extramural;Body Patterning;Somatosensory Cortex;Animals;Mice;24 Pubmed search results 2008;review;Nerve Growth Factors; 21 Activity-development}, Month = {2}, Nlm_Id = {9504819}, Number = {1}, Organization = {Program in Developmental Biology, Baylor College of Medicine, Houston TX, USA.}, Pages = {49-61}, Pii = {13/1/49}, Pubmed = {17229975}, Title = {Development of cortical maps: perspectives from the barrel cortex}, Uuid = {3DB9F16C-328B-4FC1-8377-72AA9C49663D}, Volume = {13}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1177/1073858406296257}} @article{Ince-Dunn:2006, Abstract = {During cortical development, both activity-dependent and genetically determined mechanisms are required to establish proper neuronal connectivity. While activity-dependent transcription may link the two processes, specific transcription factors that mediate such a process have not been identified. We identified the basic helix-loop-helix (bHLH) transcription factor Neurogenic Differentiation 2 (NeuroD2) in a screen for calcium-regulated transcription factors and report that it is required for the proper development of thalamocortical connections. In neuroD2 null mice, thalamocortical axon terminals fail to segregate in the somatosensory cortex, and the postsynaptic barrel organization is disrupted. Additionally, synaptic transmission is defective at thalamocortical synapses in neuroD2 null mice. Total excitatory synaptic currents are reduced in layer IV in the knockouts, and the relative contribution of AMPA and NMDA receptor-mediated currents to evoked responses is decreased. These observations indicate that NeuroD2 plays a critical role in regulating synaptic maturation and the patterning of thalamocortical connections.}, Author = {Ince-Dunn, Gulayse and Hall, Benjamin J. and Hu, Shu-Ching C. and Ripley, Beth and Huganir, Richard L. and Olson, James M. and Tapscott, Stephen J. and Ghosh, Anirvan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Trans-Activation (Genetics);Drug Interactions;Animals, Newborn;Mice;Somatosensory Cortex;Membrane Potentials;Calcium Channel Blockers;research support, n.i.h., extramural ;Receptors, AMPA;Cells, Cultured;Gene Expression;Basic Helix-Loop-Helix Transcription Factors;Potassium Chloride;Neuropeptides;Mice, Knockout;Nerve Growth Factors;Electric Stimulation;comparative study ;Synapses;S100 Proteins;24 Pubmed search results 2008;Excitatory Amino Acid Antagonists;Nimodipine;Thalamus;Embryo;Quinoxalines;Vibrissae;GABA Antagonists;Amino Acid Sequence;Egtazic Acid;Neurons;2-Amino-5-phosphonovalerate;Chelating Agents;Immunohistochemistry;Neural Pathways;research support, non-u.s. gov't ;Phosphopyruvate Hydratase;Pyridinium Compounds;Transfection;Pyridazines;10 Development;Animals;Amino Acids;10 Structural plasticity;CREB-Binding Protein;Blotting, Western;in vitro ;Chloramphenicol O-Acetyltransferase;Models, Biological;Patch-Clamp Techniques}, Month = {3}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, Pages = {683-95}, Pii = {S0896-6273(06)00088-2}, Pubmed = {16504944}, Title = {Regulation of thalamocortical patterning and synaptic maturation by NeuroD2}, Uuid = {39A1F072-7A53-495F-B1FD-6D93F70ADAD0}, Volume = {49}, Year = {2006}, url = {papers/Ince-Dunn_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.01.031}} @article{Innocenti:2001, Abstract = {We report on the case of a 20-year-old man with bilateral parasagittal parieto-occipital polymicrogyria and epilepsy. Functional magnetic resonance imaging responses to reversing checkerboard and interhemispheric electroencephalogram coherence changes to moving gratings were investigated. Results of both studies indicate that the polymicrogyric cortex was activated by visual stimuli, suggesting preserved function in the dysplastic area.}, Author = {Innocenti, G. M. and Maeder, P. and Knyazeva, M. G. and Fornari, E. and Deonna, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {Visual Cortex;Epilepsy;Photic Stimulation;Magnetic Resonance Imaging;Adult;Electroencephalography;Human;Depth Perception;Not relevant;11 Glia;Parietal Lobe;Motion Perception;Support, Non-U.S. Gov't;Male;Nervous System Malformations;case reports}, Medline = {21563356}, Month = {11}, Nlm_Id = {7707449}, Number = {5}, Organization = {Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Giorgio.Innocenti\@neuro.ki.se}, Pages = {672-6}, Pubmed = {11706976}, Title = {Functional activation of microgyric visual cortex in a human}, Uuid = {0AF2995F-110E-4FB8-89F5-E25EC62E8837}, Volume = {50}, Year = {2001}} @article{Innocenti:1978, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0003-9829}, Journal = {Arch Ital Biol}, Keywords = {Visual Cortex;Cats;Neural Pathways;Not relevant;11 Glia;Brain Mapping;Somatosensory Cortex;Animals;Visual Pathways;Corpus Callosum}, Medline = {79164734}, Month = {9}, Nlm_Id = {0372441}, Number = {3-4}, Pages = {463-70}, Pubmed = {749727}, Title = {Postnatal development of interhemispheric connections of the cat visual cortex}, Uuid = {50B30AB1-86BE-476C-86CE-A018DCA3B3EB}, Volume = {116}, Year = {1978}} @article{Innocenti:1980, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0003-9829}, Journal = {Arch Ital Biol}, Keywords = {Electric Stimulation;Axonal Transport;Cats;Not relevant;11 Glia;Support, Non-U.S. Gov't;Animals;Visual Pathways;Neurons;Corpus Callosum}, Medline = {81132667}, Month = {5}, Nlm_Id = {0372441}, Number = {2}, Pages = {124-88}, Pubmed = {6162430}, Title = {The primary visual pathway through the corpus callosum: morphological and functional aspects in the cat}, Uuid = {0BDA6F73-6596-4A42-B447-A79C9E6371B7}, Volume = {118}, Year = {1980}} @article{Innocenti:1994, Abstract = {In recent years the corpus callosum has provided a model for the study of cortical connections in the adult and developing brain. In particular, aspects of development originally described in the corpus callosum could be generalized to other cortical connections. New frontiers include the analysis of the human corpus callosum, studies of callosal connections at the cellular level and the analysis of dynamic interactions between the hemispheres. Gross morphological parameters of the human corpus callosum have been measured and related to gender, handedness etc. The detailed dendritic and axonal morphology of individual callosal neurons and their development is being defined. Electrophysiological investigations and computer stimulations are stressing temporal aspects of the interactions between the hemispheres.}, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {Corpus Callosum;Axons;Dendrites;Human;Neural Pathways;Not relevant;11 Glia;review, tutorial;Synaptic Transmission;Animals;Support, Non-U.S. Gov't;Cerebral Cortex;review;Dominance, Cerebral}, Medline = {95142911}, Month = {10}, Nlm_Id = {8004872}, Number = {1-2}, Organization = {Institut d'Anatomie, Lausanne, Switzerland.}, Pages = {1-8}, Pubmed = {7840876}, Title = {Some new trends in the study of the corpus callosum}, Uuid = {9B83E017-B5C3-418E-A371-7A5D6365DABE}, Volume = {64}, Year = {1994}} @article{Innocenti:1983, Abstract = {Clusters of 'gitter cells' develop in the white matter of the occipital cortex of the cat at the end of the first postnatal week. These clusters, and others already present at birth, disappear by the end of the first postnatal month. The life span of the clusters in the occipital white matter corresponds to the period when transitory callosal axons are eliminated. The clusters have close contact with callosal axons and can be labeled by HRP injected in the contralateral hemisphere and transported through the corpus callosum. One of the clusters clearly forms in a part of the white matter crossed by transitory callosal axons. The 'gitter cells' might be involved in the elimination of these axons. Consistent with this hypothesis, ultrastructural observations show groups of axons completely surrounded by 'gitter cell' cytoplasm as if they were being phagocytosed.}, Author = {Innocenti, G. M. and Clarke, S. and Koppel, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Aging;Visual Cortex;Cats;Axonal Transport;Not relevant;11 Glia;Animals, Newborn;Macrophages;Support, Non-U.S. Gov't;Animals;Phagocytosis;Corpus Callosum}, Medline = {84105891}, Month = {12}, Nlm_Id = {0045503}, Number = {1}, Pages = {55-66}, Pubmed = {6198052}, Title = {Transitory macrophages in the white matter of the developing visual cortex. II. Development and relations with axonal pathways}, Uuid = {AAA0EA78-EE27-11DA-8605-000D9346EC2A}, Volume = {313}, Year = {1983}} @article{Innocenti:1983a, Abstract = {Injections of horseradish peroxidase (HRP) into the occipital cortex of the kitten and diffusing to the white matter label a widely distributed microglial population and in addition, cells with light and electron microscopic features of 'gitter cells'. The latter are concentrated in a complex and highly consistent system of interconnected clusters in the white matter of the lateral, postlateral, middle suprasylvian and posterior ectosylvian gyri, as well as on the roof of the lateral ventricle. The 'gitter cells' have the ultrastructural and (as described by others) chemical characteristics of macrophages, and may be involved in the elimination of transitory axons.}, Author = {Innocenti, G. M. and Koppel, H. and Clarke, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Visual Cortex;Aging;Cats;Axonal Transport;Microscopy, Electron;Not relevant;11 Glia;Macrophages;Animals, Newborn;Animals;Horseradish Peroxidase;Support, Non-U.S. Gov't}, Medline = {84105890}, Month = {12}, Nlm_Id = {0045503}, Number = {1}, Pages = {39-53}, Pubmed = {6198051}, Title = {Transitory macrophages in the white matter of the developing visual cortex. I. Light and electron microscopic characteristics and distribution}, Uuid = {AAA0E6A4-EE27-11DA-8605-000D9346EC2A}, Volume = {313}, Year = {1983}} @article{Innocenti:1984, Abstract = {A transitory projection from primary and secondary auditory areas to the contralateral and ipsilateral areas 17 and 18 exists in newborn kittens. Distinct neuronal populations project to ipsilateral areas 17-18, contralateral areas 17-18 and contralateral auditory cortex; they are at different depth in layers II, III, and IV. By postnatal day 38 the auditory to visual projections have been lost, apparently by elimination of axons rather than by neuronal death. While it was previously reported that the elimination of transitory axons is responsible for focusing the origin of callosal connections to restricted portions of sensory areas it now appears that similar events play a more general role in the organization of cortico-cortical networks. Indeed, the elimination of juvenile projections is largely responsible for determining which areas will be connected in the adult.}, Author = {Innocenti, G. M. and Clarke, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Visual Cortex;Auditory Cortex;Cats;Neural Pathways;Not relevant;11 Glia;Animals, Newborn;Support, Non-U.S. Gov't;Animals}, Medline = {84233451}, Month = {5}, Nlm_Id = {0045503}, Number = {1}, Pages = {143-8}, Pubmed = {6733534}, Title = {Bilateral transitory projection to visual areas from auditory cortex in kittens}, Uuid = {726CB281-EE56-4593-8B6F-1559B3ADAFEC}, Volume = {316}, Year = {1984}} @article{Innocenti:2002, Abstract = {Visual areas 17, 18, 19 and 21 of the ferret can be distinguished on the grounds of cytoarchitecture, myeloarchitecture and cytochrome oxidase reactivity, and with transneuronal tract-tracing from the eye. Each visual area contains callosally connected, as well as acallosal, regions. The callosal connections originate mainly from layers 2 and 3 and, more widely, from layer 6. Callosally projecting neurons and callosal terminals are organized in three roughly medio-laterally oriented bands. The posterior and intermediate bands straddle the 17/18 and 19/21 border, respectively; the third band extends along the medial bank of the lateral suprasylvian sulcus. These bands are linked by a variable number of bridges of connections that demarcate acallosal islands. The distribution of callosal connections predicts the existence of vertical meridian representations corresponding to each of the bands and of non-isotropic representations of the visual field within the bridges and islands.}, Author = {Innocenti, Giorgio M. and Manger, Paul R. and Masiello, Italo and Colin, Isabelle and Tettoni, Laurent}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Electrophysiology;Animals;Ferrets;Neural Pathways;Female;Not relevant;Dyes;11 Glia;Support, Non-U.S. Gov't;Cerebral Cortex;Molecular Probes;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Laterality;Reticular Formation;Interneurons;Tissue Fixation;Corpus Callosum;Visual Cortex;Geniculate Bodies}, Medline = {21881436}, Month = {4}, Nlm_Id = {9110718}, Number = {4}, Organization = {Division of Neuroanatomy and Brain Development, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.giorgio.innocenti\@neuro.ki.se}, Pages = {411-22}, Pubmed = {11884356}, Title = {Architecture and callosal connections of visual areas 17, 18, 19 and 21 in the ferret (Mustela putorius)}, Uuid = {47E0252E-3490-445E-AF44-D418C01B575D}, Volume = {12}, Year = {2002}} @article{Innocenti:1994a, Abstract = {We analysed the activation profiles obtained by simulating invasion of an orthodromic action potential in eleven anterogradely filled and serially reconstructed terminal arbors of callosal axons originating and terminating in areas 17 and 18 of the adult cat. This was done in order to understand how geometry relates to computational properties of axons. In the simulation, conduction from the callosal midline to the first bouton caused activation latencies of 0.9-3.2 ms, compatible with published electrophysiological values. Activation latencies of the total set of terminal boutons varied across arbors between 0.3 and 2.7 ms. Arbors distributed boutons in tangentially segregated terminal columns spanning one or, more often, several layers. Individual columns of one axon were frequently activated synchronously or else with a few hundred microseconds of each other. Synchronous activation of spatially separate columns is achieved by: (i) long primary or secondary branches of similar calibre running nearly parallel to each other for several millimetres; (ii) variations in the calibre of branches serially fed to separate columns by the same primary or secondary branch; (iii) exchange of high-order or preterminal branches across columns. The long, parallel branches blatantly violate principles of axonal economy. Simulated alterations of the axonal arbors indicate that similar spatiotemporal patterns of activity could, in principle, be obtained by less axon-costly architectures. The structure of axonal arbors, therefore, may not be determined solely by the type of spatiotemporal activation profiles it achieves in the cortex but also by other constraints, in particular those imposed by developmental mechanisms.}, Author = {Innocenti, G. M. and Lehmann, P. and Houzel, J. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Axons;Image Processing, Computer-Assisted;Cats;Action Potentials;Presynaptic Terminals;Neural Conduction;Software;Not relevant;11 Glia;Support, Non-U.S. Gov't;Visual Pathways;Cerebral Cortex;Animals;Corpus Callosum}, Medline = {95039996}, Month = {6}, Nlm_Id = {8918110}, Number = {6}, Organization = {Institu d'Anatomie, Lausanne, Switzerland.}, Pages = {918-35}, Pubmed = {7952279}, Title = {Computational structure of visual callosal axons}, Uuid = {7513E043-7A60-405B-A838-FF23E94D8A8B}, Volume = {6}, Year = {1994}} @article{Innocenti:1980a, Abstract = {Counts of callosal neurons retrogradely labeled by horseradish peroxidase (visualized using multiple substrates) were obtained in areas 17 and 18 of five kittens reared with their eyelids bilaterally sutured and of three kittens which had undergone bilateral enucleation on postnatal days 1--4. These counts were compared with those obtained in normal adult cats. The normal adult distribution of the callosal neurons results from the gradual postnatal reduction of a more widespread juvenile population. Binocular visual deprivation by lid suturing dramatically decreases the final number of callosal neurons and narrows their region of distribution (callosal zone) in areas 17 and 18. A less severe reduction in the final number of callosal neurons is caused by bilateral enucleation, which also increases the width of the callosal zone compared to that of normal cats. Thus, visual experience is necessary for the normal stabilization of juvenile callosal connections. However, since some callosal neurons form connections in the absence of vision, other influences capable of stabilizing juvenile callosal neurons also exist. These influences are probably antagonized by destabilizing influences or inhibited, when the eyes are intact.}, Author = {Innocenti, G. M. and Frost, D. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Visual Cortex;Aging;Visual Perception;Cats;Not relevant;11 Glia;Animals;Brain;Blindness;Neurons;Corpus Callosum}, Medline = {80246373}, Nlm_Id = {0043312}, Number = {4}, Pages = {365-75}, Pubmed = {7398830}, Title = {The postnatal development of visual callosal connections in the absence of visual experience or of the eyes}, Uuid = {2112C8E1-B05E-4191-9881-3FBE3B8D37AE}, Volume = {39}, Year = {1980}} @article{Innocenti:1980b, Abstract = {Horseradish peroxidase (HRP) was injected unilaterally into the first and second visual areas (V1 and V2; areas 17 and 18) of 20 kittens aged between 2 and 90 days and into the second somatosensory area (S2) of 16 kittens aged between 1 and 52 days. The radial and tangential (normal and parallel to the pial surface, respectively) distributions of neurones giving origin to callosal axons (callosal neurones) were studied. In adult cats, callosal efferent zones (CZs) are defined by the distribution of callosal neurones. CZs occupy in the visual cortices, tangentially and radially restricted parts of areas 17, 18, 19 of the lateral suprasylvian gyrus and in the somatosensory cortices, parts of S1 and S2. At birth, callosal neurones are distributed throughout the tangential extent of visual and somatosensory areas; they are also more widespread in depth than in the adult. During the first postnatal month, as a result of the gradual disappearance of callosal neurones from parts of the visual and somatosensory areas, the adult CZs emerge. The CZ in areas 17 and 18 undergoes a further tangential reduction during the second and third postnatal months.}, Author = {Innocenti, G. M. and Caminiti, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Visual Cortex;Corpus Callosum;Axons;Aging;Cats;Efferent Pathways;Not relevant;11 Glia;Animals, Newborn;Somatosensory Cortex;Horseradish Peroxidase;Animals;Neurons;Dominance, Cerebral}, Medline = {80156975}, Nlm_Id = {0043312}, Number = {4}, Pages = {381-94}, Pubmed = {7363973}, Title = {Postnatal shaping of callosal connections from sensory areas}, Uuid = {A8AF3508-72B5-4272-ACB0-5423DA9B7867}, Volume = {38}, Year = {1980}} @article{Innocenti:1986, Abstract = {In the course of normal development transitory corticocortical projections are formed within each hemisphere and between the two hemispheres. The organization of the transitory projections and the main events in their elimination have been investigated. Experiments on visual areas of the cat indicate that the elimination/stabilization of a fraction of the juvenile projections depends on activity.}, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0392-0461}, Journal = {Ital J Neurol Sci}, Keywords = {Cats;Haplorhini;Neuronal Plasticity;Neural Pathways;Not relevant;11 Glia;Vision;Support, Non-U.S. Gov't;Animals;Cerebral Cortex;Corpus Callosum}, Medline = {87007487}, Month = {4}, Nlm_Id = {8006502}, Pages = {25-8}, Pubmed = {3093402}, Title = {Postnatal development of corticocortical connections}, Uuid = {9E34537F-D630-474B-9422-CFCFF5EA24CF}, Volume = {Suppl 5}, Year = {1986}} @article{Innocenti:1984a, Abstract = {In newborn kittens, the anterograde transport of horseradish peroxidase, alone or bound to wheat-germ agglutinin, indicates that callosal axons have entered selectively the restricted portions of the neocortical gray matter (e.g., the area 17/18 border) which receive callosal afferents in adults. The callosal axons do also reach regions where they lack in the adult, but there they seem not to penetrate far into the gray matter. Neonatal injections of retrograde fluorescent tracers restricted to the gray matter in areas 17, 18, and posteromedial lateral suprasylvian area (PMLS) label neurons in the contralateral hemisphere only when the tracers were directed into regions known to receive callosal axons. In particular, injections near the 17/18 border label neurons in the contralateral hemisphere at the homologous site and at restricted, retinotopically corresponding locations in other visual areas: a pattern similar to the adult one. In contrast, an injection reaching the white matter of areas 17 or 18 labels a wider, continuous territory extending mediolaterally over most visual areas from 17 to posterolateral lateral suprasylvian area (PLLS) and including regions which later become acallosal; in addition, labeled neurons are found in the limbic cortex medial to area 17 and in the auditory cortex lateral to PLLS, none of which is known to project to either 17 or 18 in the adult. In flattened reconstructions of the cortex, the shape of the territory labeled by each of these injections is characteristically, although somewhat irregularly, crescent shaped; its rostrocaudal position varies with that of the injection. An injection extending into the white matter of more lateral visual areas (19, 21a, PMLS) labels callosal neurons over a similar territory, which extensively overlaps that labeled by the 17/18 border injections and likewise includes regions which are acallosal in the adult. In spite of the overlapping distribution of labeling obtained from separate injection sites, as in adults, each cytoarchitectonically (or retinotopically) defined area seems to receive from a different set of neurons, although a few neurons send bifurcating axons to more than one area. In conclusion, injections restricted to the cortical gray matter reveal a topographic organization of juvenile callosal connections similar to that of the adult. In contrast, injections extending into the white matter and adequate to reach the transitory callosal axons which appear to be confined there reveal what appears to be an earlier organization. These two organizations probably reflect different morphogenetic factors.}, Author = {Innocenti, G. M. and Clarke, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Visual Cortex;Haplorhini;Cats;Rats;Not relevant;11 Glia;Animals, Newborn;Animals;Support, Non-U.S. Gov't;Corpus Callosum}, Medline = {85080780}, Month = {12}, Nlm_Id = {0406041}, Number = {2}, Pages = {287-309}, Pubmed = {6439760}, Title = {The organization of immature callosal connections}, Uuid = {70660790-A4B0-462E-A85E-B60AD7359120}, Volume = {230}, Year = {1984}} @article{Innocenti:1988, Abstract = {In newborn kittens, cortical auditory areas (including AI and AII) send transitory projections to ipsi- and contralateral visual areas 17 and 18. These projections originate mainly from neurons in supragranular layers but also from a few in infragranular layers (Innocenti and Clarke: Dev. Brain Res. 14:143-148, '84; Clarke and Innocenti: J. Comp. Neurol. 251:1-22, '86). The postnatal development of these projections was studied with injections of anterograde tracers (wheat germ agglutinin-horseradish peroxidase [WGA-HRP]) in AI and AII and of retrograde tracers (WGA-HRP, fast blue, diamidino yellow, rhodamine-labeled latex beads) in areas 17 and 18. It was found that the projections are nearly completely eliminated in development, this, by the end of the first postnatal month. Until then, most of the transitory axons seem to remain confined to the white matter and the depth of layer VI; a few enter it further but do not appear to form terminal arbors. As for other transitory cortical projections the disappearance of the transitory axons seems not to involve death of their neurons of origin. In kittens older than 1 month and in normal adult cats, retrograde tracer injections restricted to, or including, areas 17 and 18 label only a few neurons in areas AI and AII. Unlike the situation in the kitten, nearly all of these are restricted to layers V and VI. A similar distribution of neurons projecting from auditory to visual areas is found in adult cats bilaterally enucleated at birth, which suggests that the postnatal elimination of the auditory-to-visual projection is independent of visual experience and more generally of information coming from the retina.}, Author = {Innocenti, G. M. and Berbel, P. and Clarke, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Auditory Cortex;Aging;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Visual Cortex;Cats;Axonal Transport;Efferent Pathways;Not relevant;Fluorescent Dyes;11 Glia;Ocular Physiology;Support, Non-U.S. Gov't;Animals;Horseradish Peroxidase;Wheat Germ Agglutinins}, Medline = {88285433}, Month = {6}, Nlm_Id = {0406041}, Number = {2}, Organization = {Institute of Anatomy, University of Lausanne, Switzerland.}, Pages = {242-59}, Pubmed = {2456313}, Title = {Development of projections from auditory to visual areas in the cat}, Uuid = {A2DE9782-7F96-4168-ADBB-95B2127AF365}, Volume = {272}, Year = {1988}} @article{Innocenti:1991, Abstract = {Lesions of cortical areas 17 and 18 were produced in newborn kittens by local injections of the excitotoxin ibotenic acid. In the adult this results in a microcortex which consists of superficial layers I, II and III, in the absence of granular and infragranular layers. Horseradish peroxidase, alone or wheat germ agglutinin conjugated, was injected in the microcortex or in the contralateral, intact areas 17 and 18. The microcortex maintains several connections characteristic of normal areas 17 and 18 of the cat. It receives afferents from the dLGN, and several visual areas of the ipsilateral and contralateral hemisphere. However, it has lost its projections to dLGN, superior colliculus, and, at least in part, those to contralateral visual areas. Thus some parts of the microcortex receive from, but do not project into, the corpus callosum. In addition, the microcortex maintains afferents from ipsilateral and contralateral auditory areas AI and AII which are normally eliminated in development.}, Author = {Innocenti, G. M. and Berbel, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0792-8483}, Journal = {J Neural Transplant Plast}, Keywords = {Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Visual Cortex;Ibotenic Acid;Cats;Neural Pathways;Not relevant;11 Glia;Animals, Newborn;Histocytochemistry;Neurons, Afferent;Support, Non-U.S. Gov't;Wheat Germ Agglutinins;Animals;Horseradish Peroxidase;Corpus Callosum}, Medline = {91329448}, Nlm_Id = {9104161}, Number = {1}, Organization = {Institute of Anatomy, University of Lausanne, Switzerland.}, Pages = {29-54}, Pubmed = {1714302}, Title = {Analysis of an experimental cortical network: II). Connections of visual areas 17 and 18 after neonatal injections of ibotenic acid}, Uuid = {B8AAF71A-A513-4A13-B29D-93F38E63FE4E}, Volume = {2}, Year = {1991}} @article{Innocenti:1991a, Abstract = {Lesions of cortical areas 17 and 18 have been produced in newborn kittens by local injections of the excitotoxin ibotenic acid (ibo). Twenty-four hours after an injection on postnatal days 2 or 3, the gray matter of areas 17 and 18 near the center of the injection appears completely destroyed, with the exception of a one-to-two cell-thick layer at the bottom of layer I. Intact migrating neurons and radial glia can be found light- and electron-microscopically in the region affected. During the following weeks a several hundred micron thick cortex reforms. In the adult, this cortex consists of superficial layers I, II and III as proven by cytoarchitectonics, continuity with the corresponding layers of the normal cortex and cellular composition. We believe that the recovery is due to completion of migration by neurons spared by the ibo injection. More severe destruction of cerebral cortex, i.e. complete loss of the neuronal layers or their reduction to a few cell-thick mantles can be obtained with ibo injections at the end of the second or, respectively, first postnatal week. Severity of lesion also depends on the dose of ibo injected. There are interesting similarities between the ibo-injured cortex and two human neocortical displasias: microgyria and ulegyria.}, Author = {Innocenti, G. M. and Berbel, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0792-8483}, Journal = {J Neural Transplant Plast}, Keywords = {Aging;Epilepsy;Visual Cortex;Cats;Human;Microscopy, Electron;Atropine;Female;Not relevant;Ibotenic Acid;Middle Aged;11 Glia;Animals, Newborn;Support, Non-U.S. Gov't;Brain;Animals}, Medline = {91329447}, Nlm_Id = {9104161}, Number = {1}, Organization = {Institute of Anatomy, University of Lausanne, Switzerland.}, Pages = {1-28}, Pubmed = {1868117}, Title = {Analysis of an experimental cortical network: I). Architectonics of visual areas 17 and 18 after neonatal injections of ibotenic acid; similarities with human microgyria}, Uuid = {03F7EEEE-CCA0-40F3-BA49-C7A8390F90C4}, Volume = {2}, Year = {1991}} @article{Innocenti:1985, Abstract = {The number of callosally projecting neurons (callosal neurons) which can be labeled in cortical areas 17 and 18 by horseradish peroxidase (HRP), injected in the contralateral visual cortex, is reduced to about 50\%of normal in cats reared with their eyelids bilaterally sutured. In the same animals the density of HRP anterogradely transported to areas 17 and 18 is also decreased. The apparent loss of callosal neurons is limited to layers III and IV (subzone a), whereas layer VI (subzone c) is unaffected. The effect is obtained after 3 months or more but not after 1 month of deprivation. Two months of visual experience following deprivation do not restitute a normal number of callosal neurons. However, 10 days of normal visual experience preceding the deprivation are sufficient to prevent the effects of the latter. Animals deprived of vision after a short period of normal visual experience and animals allowed normal vision after 1 month of visual deprivation have a more widespread distribution of callosal neurons than do normal animals; in this way they are similar to previously described cats reared with convergent or divergent strabismus, monocular enucleation, or monocular eyelid suture. The results suggest that: vision is actively responsible for both the maintenance and the elimination of fractions of the juvenile callosal connections; the elimination which normally takes place during the second postnatal month requires normal binocular vision; and activity-dependent competition between callosal and other axons can explain the role of vision.}, Author = {Innocenti, G. M. and Frost, D. O. and Illes, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Sensory Deprivation;Cats;Not relevant;Cell Count;11 Glia;Support, U.S. Gov't, P.H.S.;Horseradish Peroxidase;Visual Pathways;Support, Non-U.S. Gov't;Animals;Corpus Callosum}, Medline = {85133812}, Month = {2}, Nlm_Id = {8102140}, Number = {2}, Pages = {255-67}, Pubmed = {3973665}, Title = {Maturation of visual callosal connections in visually deprived kittens: a challenging critical period}, Uuid = {B8189B0B-6E0F-4E03-9496-61427C77CA00}, Volume = {5}, Year = {1985}} @article{Innocenti:1986a, Abstract = {Neurons projecting transitorily into the corpus callosum from area 17 of the cat were retrogradely labeled by the fluorescent tracer Fast Blue (FB) injected into contralateral areas 17 and 18 on postnatal days 1-5. During the second postnatal month these neurons were still labeled by the early injection, although they had eliminated their callosal axon. At this time, 15-20\%of these neurons could be retrogradely relabeled by injections of Diamidino Yellow (DY) into ipsilateral areas 17 and 18, but few or none by similar injections in the other areas that receive from area 17 (19, 21a, PMLS, 20a, 20b, DLS). Similarly, area 17 neurons projecting transitorily to contralateral area PMLS during the first postnatal week could be relabeled by DY injections in ipsilateral areas 17 and 18 but not in PMLS. Already around birth, many transitorily callosal neurons in area 17 send bifurcating axons both to contralateral areas 17 and 18 and ipsilateral area 18. It is probable that during postnatal development some of these neurons selectively eliminate their callosal axon collaterals and maintain the projection to ipsilateral area 18. In fact, some transitorily callosal neurons in area 17 can be double-labeled by simultaneous perinatal injections of FB in contralateral areas 17 and 18 and of a new long-lasting retrograde tracer, rhodamine-conjugated latex microspheres, in ipsilateral area 18. The same neurons can then be relabeled by reinjecting ipsilateral area 18 with DY during the second postnatal month. This finding, however, does not exclude the possibility that some transitorily callosal neurons send an axon to ipsilateral area 18 after eliminating their callosal axon. In conclusion, area 17 neurons that project transitorily through the corpus callosum later participate, probably permanently, in ipsilateral corticocortical projections but selectively to areas 17-18. The mechanism responsible for this selectivity is unknown, but it may be related to the differential radial distribution (i.e., to birth date) of area 17 neurons engaged in the various corticocortical projections. The problems raised by the use of long-lasting retrograde fluorescent tracers in neurodevelopmental studies and by the quantification of results of double- and triple-labeling paradigms are also discussed.}, Author = {Innocenti, G. M. and Clarke, S. and Kraftsik, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Visual Cortex;Cats;Action Potentials;Not relevant;11 Glia;Animals, Newborn;Brain Mapping;Synaptic Transmission;Animals;Support, Non-U.S. Gov't;Amidines;Corpus Callosum}, Medline = {86226482}, Month = {5}, Nlm_Id = {8102140}, Number = {5}, Pages = {1384-409}, Pubmed = {3012015}, Title = {Interchange of callosal and association projections in the developing visual cortex}, Uuid = {9133213B-23C3-4808-BC58-5FD77229DA0B}, Volume = {6}, Year = {1986}} @article{Innocenti:2003, Abstract = {The Zeitgeist favors an interpretation of schizophrenia as a condition of abnormal connectivity of cortical neurons, particularly in the prefrontal and temporal cortex. The available evidence points to reduced connectivity, a possible consequence of excessive synaptic pruning in development. A decreased thalamic input to the cerebral cortex appears likely, and developmental studies predict that this decrease should entail a secondary loss of both long- and short-range cortico-cortical connections, including connections between the hemispheres. Indeed, morphological, electrophysiological and neuropsychological studies over the last two decades suggest that the callosal connections are altered in schizophrenics. However, the alterations are subtle and sometimes inconsistent across studies, and need to be investigated further with new methodologies.}, Author = {Innocenti, G. M. and Ansermet, F. and Parnas, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1359-4184}, Journal = {Mol Psychiatry}, Keywords = {Thalamus;review, academic;Human;Neural Pathways;Not relevant;11 Glia;Support, Non-U.S. Gov't;Schizophrenia;Cerebral Cortex;review;Corpus Callosum}, Medline = {22547177}, Month = {3}, Nlm_Id = {9607835}, Number = {3}, Organization = {Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Giorgio.Innocenti\@neuro.ki.se}, Pages = {261-74}, Pii = {4001205}, Pubmed = {12660799}, Title = {Schizophrenia, neurodevelopment and corpus callosum}, Uuid = {46C6DFEC-204C-4EB4-A223-E8B2A177C815}, Volume = {8}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.mp.4001205}} @article{Innocenti:1995, Abstract = {Detailed visualization, three-dimensional reconstruction, and quantification of individual callosal axons interconnecting the visual areas 17 and 18 of the cat was undertaken in order to clarify the structural basis for interhemispheric interaction. These studies have generated the notion of macro- vs micro-organization of callosal connections. The first refers to the global distribution of callosal connections in the hemisphere as well as to the pattern of area-to-area connections. The latter refers to the fine radial and tangential distributions of individual callosal axons. A discrete disjunctive, 'columnar' pattern of termination of callosal axons, previously unknown for the visual areas, was found. The consequence of caliber and distribution of callosal axons and their branches on the dynamic properties of interhemispheric interactions were analyzed by computer simulations. These studies suggested that callosal axons could synchronize activity within and between the hemispheres in ways relevant for the 'binding' of perceptual features. These new concepts prompted a reexamination of the normal development of callosal connections. The central issue is whether intrinsic developmental programs, or else cellular interactions open to environmental information specify the morphological substrate of interhemispheric interactions. The answer to this question is still incomplete. In development, transient, widespread arbors of callosal axons, which could provide the basis for plastic changes of callosal connections were found in the white matter and the deep cortical layers. On the other hand, growth into the cortex and synaptogenesis of callosal axons appear to be highly, topographically specific albeit not necessarily independent of visual experience.}, Author = {Innocenti, G. M. and Aggoun-Zouaoui, D. and Lehmann, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0028-3932}, Journal = {Neuropsychologia}, Keywords = {Visual Cortex;Visual Pathways;Cell Differentiation;Corpus Callosum;Dominance, Cerebral;Image Processing, Computer-Assisted;Cats;Neuronal Plasticity;Not relevant;11 Glia;review, tutorial;Synaptic Transmission;Support, Non-U.S. Gov't;Animals;Mice;review;Axons}, Medline = {96059977}, Month = {8}, Nlm_Id = {0020713}, Number = {8}, Organization = {Institut d'Anatomie, Universit{\'e} de Lausanne, Switzerland.}, Pages = {961-87}, Pii = {002839329500033Y}, Pubmed = {8524456}, Title = {Cellular aspects of callosal connections and their development}, Uuid = {646ACBB4-1368-4834-BC06-EA4C7EC2B3B4}, Volume = {33}, Year = {1995}} @article{Innocenti:1983b, Abstract = {In areas 17 and 18 of adult cats only a few neurons send bifurcating axons to more than one contralateral area or to areas in both hemispheres; most neurons seem to project to only one area. We now found that such a selective connectivity is already present at birth, i.e. several weeks before transitory callosal axons are eliminated. This is true even for those portions of cortex which will lose access to the corpus callosum: in particular different neurons project transitorily from medial area 17 to different contralateral areas. Thus cortical neurons may be induced to project to specific targets by a mechanism operating long before (and possibly independent of) the axon elimination. The latter may, however, be responsible for the final topographic organization of the connections.}, Author = {Innocenti, G. M. and Clarke, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Visual Cortex;Cats;Not relevant;11 Glia;Brain Mapping;Synaptic Transmission;Animals, Newborn;Support, Non-U.S. Gov't;Animals;Neurons;Corpus Callosum}, Medline = {84068803}, Month = {10}, Nlm_Id = {7600130}, Number = {1-2}, Pages = {27-32}, Pubmed = {6316218}, Title = {Multiple sets of visual cortical neurons projecting transitorily through the corpus callosum}, Uuid = {BD7FB43B-0BD7-441A-8509-A27AD66B699D}, Volume = {41}, Year = {1983}} @article{Innocenti:1982, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0028-3967}, Journal = {Neurosci Res Program Bull}, Keywords = {Dominance, Cerebral;Animals;Aging;Thalamic Nuclei;Rats;Neural Pathways;Axons;Not relevant;11 Glia;Pyramidal Tracts;Computers;Cerebral Cortex;Neurons;Mice;Microscopy, Electron;Corpus Callosum;Models, Neurological;Cats;Brain Mapping}, Medline = {83013416}, Month = {4}, Nlm_Id = {7509226}, Number = {4}, Pages = {532-40}, Pubmed = {7121841}, Title = {Development of interhemispheric cortical connections}, Uuid = {E707A0AC-DA97-4346-AE6F-0FDA849EEB38}, Volume = {20}, Year = {1982}} @article{Innocenti:1979, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0079-6123}, Journal = {Prog Brain Res}, Keywords = {Visual Cortex;Corpus Callosum;Neurons, Efferent;Cats;Rats;Not relevant;11 Glia;Animals, Newborn;Neurons, Afferent;Animals;Brain;Somatosensory Cortex;Axons}, Medline = {81014716}, Nlm_Id = {0376441}, Pages = {479-87}, Pubmed = {551492}, Title = {Two types of brain plasticity?}, Uuid = {60A5CD27-BCEC-4E31-A066-D95C316044A2}, Volume = {51}, Year = {1979}} @article{Innocenti:1999, Abstract = {MS is a little girl who suffered severe, bilateral destruction of her primary visual areas at six weeks, after premature birth at 30 weeks. Between the ages of 4.5 and 5.5 years she partially recovered different aspects of visual function, and, in particular, the ability to segregate fig-ures from background, based on texture cues. The recovery might have been due to the compensatory role of the remaining visual areas that could have acquired response properties similar to those of the primary visual areas. This is not supported by the available FMRI (functional magnetic resonance imaging) responses to visual stimuli. Instead, abnormalities in the pattern of stimulus-induced changes of interhemi-spheric EEG-coherence in this patient suggest that her visual callosal connections, and possibly other cortico-cortical connections have re-organized abnormally. Since cortico-cortical connections, including the callosal ones appear to be involved in perceptual binding and figure-background segregation, their reorganization could be an important element in the functional recovery after early lesion, and/or in the residual perceptual impairment.}, Author = {Innocenti, G. M. and Kiper, D. C. and Knyazeva, M. G. and Deonna, T. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0922-6028}, Journal = {Restor Neurol Neurosci}, Keywords = {Not relevant;11 Glia}, Nlm_Id = {9005499}, Number = {2-3}, Organization = {Division of Neuroanatomy and Brain Development, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.}, Pages = {219-27}, Pubmed = {12671234}, Title = {On nature and limits of cortical developmental plasticity after an early lesion, in a child}, Uuid = {C57BAEC0-1E15-4768-8478-138F76586AC3}, Volume = {15}, Year = {1999}} @article{Innocenti:1996, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0035-3655}, Journal = {Rev Med Suisse Romande}, Keywords = {History of Medicine, 20th Cent.;United States;Switzerland;Human;Neurosciences;historical article;Europe;11 Glia;Not relevant;Neuroanatomy;Brain}, Medline = {97122873}, Month = {11}, Nlm_Id = {0421524}, Number = {11}, Organization = {Institut de biologie cellulaire et de morphologie, Facult{\'e} de m{\'e}decine, Universit{\'e} de Lausanne.}, Pages = {931-42}, Pubmed = {8992591}, Title = {[The neuroanatomic melting pot of Lausanne (1973-1993)]}, Uuid = {2B539BA9-6422-46C8-84E6-6EC118DEBD02}, Volume = {116}, Year = {1996}} @article{Innocenti:1981, Abstract = {The visual cortical areas in the two hemispheres are interconnected by axons running through the corpus callosum. In adult cats, these axons originate from, and terminate in, tangentially restricted portions of each area. In young kittens, however, callosal axons originate from the entire extent of each area, although they apparently enter the gray matter only in the restricted regions where they will also be found in adults. In kittens, but not in adults, callosal axons also reach other regions, but there they appear to be confined to the lowest part of layer VI. During the first two postnatal months, the callosal efferent zones become progressively restricted to their adult locations. During this process, many neurons eliminate the axons (or axon collaterals) that they had formerly sent through the corpus callosum and form permanent connection ipsilaterally.}, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Corpus Callosum;Cats;Not relevant;11 Glia;Support, Non-U.S. Gov't;Animals;Age Factors;Visual Pathways;Axons}, Medline = {81177079}, Month = {5}, Nlm_Id = {0404511}, Number = {4496}, Pages = {824-7}, Pubmed = {7221566}, Title = {Growth and reshaping of axons in the establishment of visual callosal connections}, Uuid = {9E7AED33-EE27-11DA-8605-000D9346EC2A}, Volume = {212}, Year = {1981}, url = {papers/Innocenti_Science1981.pdf}} @article{Innocenti:1995a, Abstract = {The callosal visual connections of the cat provide a model for studying the phenotypes of cortical axons and their differentiation. The terminal arbor of a callosal axon develops in several successive stages. At each stage, the arbor approximates the adult phenotype more closely. This is achieved through two mechanisms: (1) exuberant, but increasingly constrained, growth and (2) partial deletion of previously generated parts of the arbor. This differentiation is controlled by interactions of the axon with its cellular environment, and by visual experience. It might have played a permissive role in the evolution of the cerebral cortex by enabling adjustments of cortical connectivity to changes in the number, size, internal organization and cellular composition of cortical areas. 0166-2236 Journal Article Review Review, Tutorial}, Author = {Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Human;Neural Pathways/cytology/growth &development/physiology;Animals;Axons/physiology;Neural Pathways;review, tutorial;review;*Evolution;Axons;11 Glia;N;19 Neocortical evolution;Evolution;Support, Non-U.S. Gov't;Cerebral Cortex;Cerebral Cortex/cytology/growth &development/*physiology;Cats}, Medline = {96048681}, Month = {9}, Nlm_Id = {7808616}, Number = {9}, Organization = {Institut d'Anatomie, Lausanne, Switzerland.}, Pages = {397-402}, Pii = {016622369593936R}, Pubmed = {7482805}, Title = {Exuberant development of connections, and its possible permissive role in cortical evolution}, Uuid = {9C3457D8-00AB-11DB-9E68-000D9346EC2A}, Volume = {18}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7482805}} @article{Inoue:2001, Author = {Inoue, T. and Krumlauf, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:49 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Embryo;Gene Transfer Techniques;Gene Expression Regulation, Developmental;23 Technique;Cell Culture;review, tutorial;Electroporation;Support, Non-U.S. Gov't;Animals;Brain;review;Genetic Vectors}, Medline = {21547536}, Month = {11}, Nlm_Id = {9809671}, Organization = {Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, Missouri 64110, USA.rek\@stowers-institute.org}, Pages = {1156-8}, Pii = {nn1101-1156}, Pubmed = {11687822}, Title = {An impulse to the brain--using in vivo electroporation}, Uuid = {A5054AFB-51F9-4E77-9EC8-0B7290FE65E9}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Inoue_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1101-1156}} @article{Insausti:2001, Abstract = {Episodic memory consolidation requires the integrity of the anatomical pathways between the cerebral cortex and the hippocampal formation. Whilst the largest cortical output of the hippocampal formation originates in the entorhinal cortex, direct projections from CA1, subiculum and presubiculum to the cortex have been reported. The aim of this study is the assessment of the extent, topography and relative strength of those projections, as a parallel/alternate route of memory processing. A total of 45 injections in 28 Macaca fascicularis monkeys were used. Cortical deposits of fluorescent tracers (20 cases, 3\%Fast Blue, 2\%Diamidino Yellow) or 1\%WGA-HRP (eight cases) were made in different cortical areas of the frontal, temporal and parietal lobes, as well as cingulate cortex by direct exposure of the cortical surface. After appropriate survival, animals were perfused and the brains serially sectioned at 50 microm and the retrograde labelling charted with an X-Y digitizing system. Retrograde neuronal labelling was observed in CA1, subiculum, presubiculum and parasubiculum; it was absent in the dentate gyrus, CA3 and CA2. Compared to other portions of the hippocampal formation, the CA1-subiculum border had the highest number of labelled neurons (especially after deposits in the rostral perirhinal cortex), followed by medial frontal cortex, temporal pole, orbitofrontal, anterior and posterior cingulate cortices, parietal and inferotemporal cortices, and no labelling after posterior inferotemporal and lateral frontal cortices. Our results indicate that CA1, subiculum, presubiculum and parasubiculum send direct output to cortical areas. This nonentorhinal, hippocampal formation cortical output may be relevant in memory processing.}, Author = {Insausti, R. and Mu\~{n}oz, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {24 Pubmed search results 2008;Dyes;Research Support, Non-U.S. Gov't;Hippocampus;Neural Pathways;Macaca fascicularis;Tissue Fixation;Brain Mapping;Animals;Entorhinal Cortex;Male;Neurons;Cerebral Cortex}, Medline = {21437563}, Month = {8}, Nlm_Id = {8918110}, Number = {3}, Organization = {Human Neuroanatomy Laboratory, Department of Health Sciences, University of Castilla-La Mancha, School of Medicine, Benjam{\'\i}n Palencia Building, Campus Universitario s/n, 02071 Albacete, Spain. rinsaus\@med-ab.uclm.es}, Pages = {435-51}, Pii = {ejn1662}, Pubmed = {11553294}, Title = {Cortical projections of the non-entorhinal hippocampal formation in the cynomolgus monkey (Macaca fascicularis)}, Uuid = {46AAA621-6371-4381-8E20-A944027924DE}, Volume = {14}, Year = {2001}} @article{Iosif:2006, Abstract = {Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine, acting through the TNF-R1 and TNF-R2 receptors. The two receptors have been proposed to mediate distinct TNF-alpha effects in the CNS, TNF-R1 contributing to neuronal damage and TNF-R2 being neuroprotective. Whether TNF-alpha and its receptors play any role for neurogenesis in the adult brain is unclear. Here we used mouse models with loss of TNF-R1 and TNF-R2 function to establish whether signaling through these receptors could influence hippocampal neurogenesis in vivo under basal conditions, as well as after status epilepticus (SE), which is associated with inflammation and elevated TNF-alpha levels. Notably, in the intact brain, the number of new, mature hippocampal neurons was elevated in TNF-R1(-/-) and TNF-R1/R2(-/-) mice, whereas no significant changes were detected in TNF-R2(-/-) mice. Also after SE, the TNF-R1(-/-) and TNF-R1/R2(-/-) mice produced more new neurons. In contrast, the TNF-R2(-/-) mice showed reduced SE-induced neurogenesis. Cell proliferation in the dentate subgranular zone was elevated in TNF-R1(-/-) and TNF-R1/R2(-/-) mice both under basal conditions and after SE. The TNF-R2(-/-) mice either showed no change or minor decrease of cell proliferation. TNF-R1 and TNF-R2 receptors were expressed by hippocampal progenitors, as assessed with reverse transcription-PCR on sorted or cultured cells and immunocytochemistry on cultures. Our data reveal differential actions of TNF-R1 and TNF-R2 signaling in adult hippocampal neurogenesis and identify for the first time TNF-R1 as a negative regulator of neural progenitor proliferation in both the intact and pathological brain.}, Author = {Iosif, Robert E. and Ekdahl, Christine T. and Ahlenius, Henrik and Pronk, Cornelis J. H. and Bonde, Sara and Kokaia, Zaal and Jacobsen, Sten-Eirik W. E. and Lindvall, Olle}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {14 Immune;04 Adult neurogenesis factors;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8102140}, Number = {38}, Organization = {Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE 221 84 Lund, Sweden.}, Pages = {9703-12}, Pii = {26/38/9703}, Pubmed = {16988041}, Title = {Tumor necrosis factor receptor 1 is a negative regulator of progenitor proliferation in adult hippocampal neurogenesis}, Uuid = {71C7A512-9E21-4CD2-893D-371D545EBD16}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2723-06.2006}} @article{Iravani:2005, Abstract = {Sustained reactive microgliosis may contribute to the progressive degeneration of nigral dopaminergic neurons in Parkinson's disease (PD), in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposed human and in non-human primates. However, the temporal relationship between glial cell activation and nigral cell death is relatively unexplored. Consequently, the effects of acute (24 h) and chronic (30 days) glial cell activation induced by unilateral supranigral lipopolysaccharide (LPS) administration were studied in rats. At 24 h, LPS administration caused a marked reduction in the number of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra (SN) but striatal TH-ir was unaffected. By 30 days, the loss of TH-positive neurons in the LPS-treated nigra was no greater than at 24 h although a heterogeneous loss of striatal TH-ir was present. The loss of nigrostriatal neurons was of functional significance, as at 30 days, LPS-treated rats exhibited ipsiversive circling in response to (+)-amphetamine administration. At 24 h, there was a moderate increase in glial fibrillary acidic protein (GFAP)-ir astrocytes in the SN but a marked elevation of p47phox positive OX-42-ir microglia, and intense inducible nitric oxide synthase (iNOS)-ir and 3-nitrotyrosine (3-NT)-ir was present. However, by 30 days the morphology of OX-42-ir microglia returned to a resting state, the numbers were greatly reduced and no 3-NT-ir was present. At 30 days, GFAP-ir astrocytes were markedly increased in number and iNOS-ir was present in fibrillar astrocyte-like cells. This study shows that acute glial activation leading to dopaminergic neuron degeneration is an acute short-lasting response that does not itself perpetuate cell death or lead to prolonged microglial activation.}, Author = {Iravani, and Leung, and Sadeghian, and Haddon, and Rose, and Jenner,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Alpha;11 Glia}, Month = {7}, Nlm_Id = {8918110}, Number = {2}, Organization = {Neurodegenerative Disease Research Centre, GKT School of Biomedical Sciences, King's College, London, SE11UL, UK.}, Pages = {317-330}, Pii = {EJN4220}, Pubmed = {16045485}, Title = {The acute and the long-term effects of nigral lipopolysaccharide administration on dopaminergic dysfunction and glial cell activation}, Uuid = {AA1BA458-8B77-41B9-925C-49A31EF84F09}, Volume = {22}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2005.04220.x}} @article{Isaacson:1973, Author = {Isaacson, R. L. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Epilepsy;Electric Stimulation;Electroencephalography;21 Epilepsy;21 Neurophysiology;Hypothalamus;Rats;Penicillin G;Disease Models, Animal;Male;Cerebral Cortex;Animals;24 Pubmed search results 2008}, Medline = {73160170}, Month = {1}, Nlm_Id = {0045503}, Number = {1}, Pages = {194-9}, Pii = {0006-8993(73)90413-7}, Pubmed = {4698156}, Title = {Hypothalamic stimulation and the persistence of epileptiform discharges}, Uuid = {1C9917D0-1750-4C10-9E7A-86CDCF4D96A9}, Volume = {49}, Year = {1973}} @article{Isaacson:1971, Author = {Isaacson, R. L. and Schwartz, H. and Persoff, N. and Pinson, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Epilepsy;21 Epilepsy;Electroencephalography;21 Neurophysiology;Rats;Penicillin G;Synaptic Transmission;Animals;Male;Cerebral Cortex;24 Pubmed search results 2008;Corpus Callosum}, Medline = {71290228}, Month = {6}, Nlm_Id = {2983306R}, Number = {2}, Pages = {133-46}, Pubmed = {4328332}, Title = {The role of the corpus callosum in the establishment of areas of secondary epileptiform activity}, Uuid = {8D5352CC-D1A4-4D8B-AE94-02F1061701BE}, Volume = {12}, Year = {1971}} @article{Isgor:2005, Abstract = {Numerous factors modulate neurogenesis in the adult dentate gyrus and subventricular zone, but it is often not clear if the modulation is mediated by direct effects on the proliferating and differentiating cells or secondary to effects on other cells. Also, while some factors selectively affect neurogenesis in one of the neurogenetic zones, it is not clear how selectivity is achieved. Estrogen is a hormonal modulator of neurogenesis. To address the issues of direct versus indirect control and regional specificity we investigated the colocalization of immunoreactivity for a proliferating cell marker, Ki-67, and a marker for migrating and differentiating cells with a neuronal phenotype, doublecortin, with the expressions of mRNA for estrogen receptors alpha and beta. We found an extensive colocalization of estrogen receptor alpha with both markers in the dentate gyrus and only with Ki-67 in the subventricular zone. An extensive colocalization of estrogen receptor beta with both markers was found in the dentate gyrus, but only a few Ki-67-immunoreactive and no doublecortin-immunoreactive cells of the subventricular zone expressed estrogen receptor beta mRNA. Estrogen receptor alpha and beta mRNAs were not expressed in other telencephalic Ki-67-immunoreactive cells or in constitutively doublecortin-immunoreactive cells of the piriform cortex. The extensive colocalization of immunoreactive markers for cell proliferation and differentiation with mRNAs for estrogen receptor alpha and estrogen receptor beta points to the direct modulation of dentate cell proliferation, differentiation and survival by estrogen, while direct effects of estrogen in the subventricular zone appear restricted to estrogen receptor alpha-mediated effects operating at the time of cell proliferation.}, Author = {Isgor, and Watson,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7605074}, Organization = {Department of Biomedical Science, Charles E. Schmidt Biomedical Center, Florida Atlantic University, Boca Raton, FL 33431-0991, USA.}, Pii = {S0306-4522(05)00512-9}, Pubmed = {15994024}, Title = {Estrogen receptor alpha and beta mRNA expressions by proliferating and differentiating cells in the adult rat dentate gyrus and subventricular zone}, Uuid = {211598C6-3E3D-4AE5-BE44-E1D86A55250E}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2005.05.008}} @article{Ishiguro:1965, Author = {Ishiguro, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0033-2658}, Journal = {Seishin Shinkeigaku Zasshi}, Keywords = {21 Neurophysiology;Anoxia;Electrophysiology;Brain;24 Pubmed search results 2008;21 Epilepsy}, Medline = {66002132}, Month = {5}, Nlm_Id = {9801787}, Number = {5}, Pages = {435-56}, Pubmed = {5889889}, Title = {[Anoxia and electrical activity of the brain--comparative studies on the neocortex, the paleocortex, the archicortex and the subcortical structures]}, Uuid = {2E01C4C6-A0B5-40AD-8346-9EEC7795D4A8}, Volume = {67}, Year = {1965}} @article{Ivanov:2006, Abstract = {The extracellular signal-regulated kinases (ERK) signalling cascade is a key pathway that mediates the NMDA receptor (NMDAR)-dependent neuronal plasticity and survival. However, it is not clear yet how NMDARs regulate ERK activity. Stimulation of the NMDARs induces a complex modification of ERK that includes both ERK activation and inactivation and depends on particular experimental conditions. Here we show that there exists a differential restriction in the regulation of ERK activity that depends on the pool of NMDAR that was activated. The synaptic pool of NMDARs activates ERK whereas the extrasynaptic pool does not; on the contrary, it triggers a signalling pathway that results in the inactivation of ERK. As a result, simultaneous activation of both extrasynaptic and synaptic NMDAR using bath application of NMDA or glutamate (a typical protocol explored in the majority of studies) produced ERK activation that depended on the concentration of agonists and was always significantly weaker than those mediated by synaptic NMDARs. Since the activation of the extrasynaptic NMDA is attributed mainly to global release of glutamate occurring at pathological conditions including hypoxic/ischaemic insults, traumas and epileptic brain damage, the reported differential regulation of ERK cascade by NMDARs provides a unique mechanism for an early identification of the physiological and/or pathophysiological consequences of NMDAR activation. The negative regulation of the ERK activity might be one of the first signalling events determining brain injury and constitutes a putative target of new pharmacological applications.}, Author = {Ivanov, Anton and Pellegrino, Christophe and Rama, Sylvain and Dumalska, Iryna and Salyha, Yuriy and Ben-Ari, Yehezkel and Medina, Igor}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Synapses;21 Epilepsy;Enzyme Activation;21 Neurophysiology;Action Potentials;Hippocampus;Rats;Extracellular Signal-Regulated MAP Kinases;Synaptic Transmission;Animals;Cells, Cultured;Receptors, N-Methyl-D-Aspartate;Neurons;24 Pubmed search results 2008}, Medline = {103133006}, Month = {5}, Nlm_Id = {0266262}, Number = {Pt 3}, Organization = {INMED/INSERM Unite 29, 163 Route de Luminy, 13009 Marseille, France.}, Pages = {789-98}, Pii = {jphysiol.2006.105510}, Pubmed = {16513670}, Title = {Opposing role of synaptic and extrasynaptic NMDA receptors in regulation of the extracellular signal-regulated kinases (ERK) activity in cultured rat hippocampal neurons}, Uuid = {656FC2AE-09A6-4E86-B34F-46BD04FAD168}, Volume = {572}, Year = {2006}, url = {papers/Ivanov_JPhysiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2006.105510}} @article{Iwasato:2008, Abstract = {Experimental evidence from mutant or genetically altered mice indicates that the formation of barrels and the proper maturation of thalamocortical (TC) synapses in the primary somatosensory (barrel) cortex depend on mechanisms mediated by neural activity. Type 1 adenylyl cyclase (AC1), which catalyzes the formation of cAMP, is stimulated by increases in intracellular Ca(2+) levels in an activity-dependent manner. The AC1 mutant mouse, barrelless (brl), lacks typical barrel cytoarchitecture, and displays presynaptic and postsynaptic functional defects at TC synapses. However, because AC1 is expressed throughout the trigeminal pathway, the barrel cortex phenotype of brl mice may be a consequence of AC1 disruption in cortical or subcortical regions. To examine the role of cortical AC1 in the development of morphological barrels and TC synapses, we generated cortex-specific AC1 knock-out (CxAC1KO) mice. We found that neurons in layer IV form grossly normal barrels and TC axons fill barrel hollows in CxAC1KO mice. In addition, whisker lesion-induced critical period plasticity was not impaired in these mice. However, we found quantitative reductions in the quality of cortical barrel cytoarchitecture and dendritic asymmetry of layer IV barrel neurons in CxAC1KO mice. Electrophysiologically, CxAC1KO mice have deficits in the postsynaptic but not in the presynaptic maturation of TC synapses. These results suggest that activity-dependent postsynaptic AC1-cAMP signaling is required for functional maturation of TC synapses and the development of normal barrel cortex cytoarchitecture. They also suggest that the formation of the gross morphological features of barrels is independent of postsynaptic AC1 in the barrel cortex.}, Author = {Iwasato, Takuji and Inan, Melis and Kanki, Hiroaki and Erzurumlu, Reha S. and Itohara, Shigeyoshi and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;Thalamus;24 Pubmed search results 2008;research support, non-u.s. gov't;Excitatory Postsynaptic Potentials;Mice, Knockout;Female;Neuronal Plasticity;Neural Pathways;Mice, Mutant Strains;comparative study;research support, n.i.h., extramural;Animals;Male;Cerebral Cortex;Adenylate Cyclase;Mice}, Month = {6}, Nlm_Id = {8102140}, Number = {23}, Organization = {Laboratory for Behavioral Genetics, RIKEN Brain Science Institute, Saitama 351-0198, Japan.}, Pages = {5931-43}, Pii = {28/23/5931}, Pubmed = {18524897}, Title = {Cortical adenylyl cyclase 1 is required for thalamocortical synapse maturation and aspects of layer IV barrel development}, Uuid = {CE108406-ECFB-4C27-B60E-3D5D40FAEF2B}, Volume = {28}, Year = {2008}, url = {papers/Iwasato_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0815-08.2008}} @article{Izhikevich:2004, Abstract = {A neuronal network inspired by the anatomy of the cerebral cortex was simulated to study the self-organization of spiking neurons into neuronal groups. The network consisted of 100 000 reentrantly interconnected neurons exhibiting known types of cortical firing patterns, receptor kinetics, short-term plasticity and long-term spike-timing-dependent plasticity (STDP), as well as a distribution of axonal conduction delays. The dynamics of the network allowed us to study the fine temporal structure of emerging firing patterns with millisecond resolution. We found that the interplay between STDP and conduction delays gave rise to the spontaneous formation of neuronal groups--sets of strongly connected neurons capable of firing time-locked, although not necessarily synchronous, spikes. Despite the noise present in the model, such groups repeatedly generated patterns of activity with millisecond spike-timing precision. Exploration of the model allowed us to characterize various group properties, including spatial distribution, size, growth, rate of birth, lifespan, and persistence in the presence of synaptic turnover. Localized coherent input resulted in shifts of receptive and projective fields in the model similar to those observed in vivo.}, Author = {Izhikevich, Eugene M. and Gally, Joseph A. and Edelman, Gerald M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008;research support, non-u.s. gov't;Statistics as Topic;21 Neurophysiology;Action Potentials;Neuronal Plasticity;Models, Neurological;Computer Simulation;evaluation studies;Rabbits;Nerve Net;Animals;Humans;Cerebral Cortex;Neurons;Synaptic Transmission}, Month = {8}, Nlm_Id = {9110718}, Number = {8}, Organization = {The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, CA 92121, USA. eugene.izhikevich\@nsi.edu}, Pages = {933-44}, Pii = {bhh053}, Pubmed = {15142958}, Title = {Spike-timing dynamics of neuronal groups}, Uuid = {2757B4C6-F955-4DA9-9763-414966F13845}, Volume = {14}, Year = {2004}, url = {papers/Izhikevich_CerebCortex2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh053}} @article{Jackson:2002, Abstract = {Primary microcephaly (MIM 251200) is an autosomal recessive neurodevelopmental condition in which there is a global reduction in cerebral cortex volume, to a size comparable with that of early hominids. We previously mapped the MCPH1 locus, for primary microcephaly, to chromosome 8p23, and here we report that a gene within this interval, encoding a BRCA1 C-terminal domain-containing protein, is mutated in MCPH1 families sharing an ancestral 8p23 haplotype. This gene, microcephalin, is expressed in the developing cerebral cortex of the fetal brain. Further study of this and related genes may provide important new insights into neocortical development and evolution.}, Author = {Jackson, Andrew P. and Eastwood, Helen and Bell, Sandra M. and Adu, Jimi and Toomes, Carmel and Carr, Ian M. and Roberts, Emma and Hampshire, Daniel J. and Crow, Yanick J. and Mighell, Alan J. and Karbani, Gulshan and Jafri, Hussain and Rashid, Yasmin and Mueller, Robert F. and Markham, Alexander F. and Woods, C. Geoffrey}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0002-9297}, Journal = {Am J Hum Genet}, Keywords = {10 Development;Chromosomes, Human, Pair 8;Animals;Cloning, Molecular;Humans;Base Sequence;Gene Expression Regulation, Developmental;Sequence Homology, Amino Acid;DNA;Brain;Female;Child;Microcephaly;RNA, Messenger;research support, non-u.s. gov't;Male;Embryonic and Fetal Development;In Situ Hybridization;10 genetics malformation;Adult;Organ Size;DNA Mutational Analysis;Mice;24 Pubmed search results 2008;Amino Acid Sequence;Molecular Sequence Data;Nerve Tissue Proteins;Adolescent}, Month = {7}, Nlm_Id = {0370475}, Number = {1}, Organization = {Molecular Medicine Unit, University of Leeds, United Kingdom. medapj\@leeds.ac.uk}, Pages = {136-42}, Pii = {AJHG023908}, Pubmed = {12046007}, Title = {Identification of microcephalin, a protein implicated in determining the size of the human brain}, Uuid = {0E7D5DA5-9A14-42AD-B963-277674308B69}, Volume = {71}, Year = {2002}} @article{Jackson:1989, Abstract = {The production of ferret visual cortical neurons was studied using 3H-thymidine autoradiography. The genesis of cortical neurons begins on or slightly before embryonic day 20 (E20) of the 41 d gestational period, continues postnatally until 2 weeks after birth (P14), and follows an inside-out radial gradient with neurons for the deeper cortical layers being generated before those for the superficial layers. Layer I neurons are generated both early (E20-E30) and late (P1-P14) in the period of cortical neurogenesis and, thus, provide at least a partial exception to the inside-out gradient of cortical neurogenesis. Tangential gradients of cortical neurogenesis extend across areas 17 and 18 in both the anterior-to-posterior and lateral-to-medial directions. Neither of these gradients bears a meaningful relationship to the cortical representation of the visual field. Most infragranular and granular layer neurons are generated prenatally, while most supragranular layer neurons are produced postnatally. Neurons destined for a given layer are produced over a period of several days, and the neurons generated on any given day contribute to the formation of 2 or more cortical layers. In general, prenatally generated neurons complete their migration in 1 week or less, while most postnatally generated neurons require approximately 2 weeks to complete their migration. 0270-6474 Journal Article}, Author = {Jackson, C. A. and Peduzzi, J. D. and Hickey, T. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;Ferrets/embryology/*growth &development;10 Development;Embryo/*physiology;Thymidine/diagnostic use;Autoradiography;Cell Division;Neurons/cytology/*physiology;A,F abstr;Animals, Newborn;Neuroglia/cytology;Carnivora/*growth &development;Animals;Cell Movement;Visual Cortex/cytology/embryology/*growth &development;Support, U.S. Gov't, P.H.S.}, Number = {4}, Organization = {Department of Physiological Optics, School of Optometry, Medical Center, University of Alabama, Birmingham 35294.}, Pages = {1242-53}, Pubmed = {2703875}, Title = {Visual cortex development in the ferret. I. Genesis and migration of visual cortical neurons}, Uuid = {3140CDF5-2AA2-438E-8A56-7DD37EDDBAE9}, Volume = {9}, Year = {1989}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2703875}} @article{Jackson:2006, Abstract = {Neurons and oligodendrocytes are produced in the adult brain subventricular zone (SVZ) from neural stem cells (B cells), which express GFAP and have morphological properties of astrocytes. We report here on the identification B cells expressing the PDGFRalpha in the adult SVZ. Specifically labeled PDGFRalpha expressing B cells in vivo generate neurons and oligodendrocytes. Conditional ablation of PDGFRalpha in a subpopulation of postnatal stem cells showed that this receptor is required for oligodendrogenesis, but not neurogenesis. Infusion of PDGF alone was sufficient to arrest neuroblast production and induce SVZ B cell proliferation contributing to the generation of large hyperplasias with some features of gliomas. The work demonstrates that PDGFRalpha signaling occurs early in the adult stem cell lineage and may help regulate the balance between oligodendrocyte and neuron production. Excessive PDGF activation in the SVZ in stem cells is sufficient to induce hallmarks associated with early stages of tumor formation.}, Author = {Jackson, Erica L. and Garcia-Verdugo, Jose Manuel and Gil-Perotin, Sara and Roy, Monica and Quinones-Hinojosa, Alfredo and VandenBerg, Scott and Alvarez-Buylla, Arturo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Glioma;research support, n.i.h., extramural ;Signal Transduction;Animals;Humans;Middle Aged;Mice, Transgenic;comparative study ;Cell Proliferation;research support, non-u.s. gov't ;Platelet-Derived Growth Factor;Aged, 80 and over;Neurons;Mice;Receptor, Platelet-Derived Growth Factor alpha;24 Pubmed search results 2008;Stem Cells;Lateral Ventricles;Adolescent}, Month = {7}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Neurological Surgery and Program in Developmental and Stem Cell Biology, University of California, San Francisco, San Francisco, California 94143, USA.}, Pages = {187-99}, Pii = {S0896-6273(06)00466-1}, Pubmed = {16846854}, Title = {PDGFR alpha-positive B cells are neural stem cells in the adult SVZ that form glioma-like growths in response to increased PDGF signaling}, Uuid = {2B7EF72C-EE6C-4F09-AFA8-90D6D860DD8E}, Volume = {51}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.06.012}} @article{Jacob:1977, Abstract = {0036-8075 Journal Article}, Author = {Jacob, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Science}, Keywords = {*Science;Human;Sexual Behavior/physiology;Brain/physiology;Molecular Biology;N;Philosophy;Sociology;Animals;Reproduction;19 Neocortical evolution;*Evolution}, Number = {4295}, Pages = {1161-6}, Pubmed = {860134}, Title = {Evolution and tinkering}, Uuid = {EBCDD564-8C79-4F19-A445-D98BEC5A02DF}, Volume = {196}, Year = {1977}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=860134}} @article{Jacobs:1996, Abstract = {The presence of developmental cortical malformations has been associated with the occurrence of epilepsy, and correlative anatomic-clinical electrophysiological studies suggest that microdysgenic lesions may actually initiate epileptiform activity. We have investigated the electrophysiological properties of an animal model of polymicrogyria created by making cortical freeze lesions in rat pups at P0 or P1. Such lesions create microgyri with histological features similar to those of human polymicrogyria. We have determined that there is a focal region of hyperexcitability around the lesion in this rat microgyrus. Field potentials evoked by stimulation within a few millimeters of the microgyrus have characteristics typical of epileptiform activity. This aberrant activity is seen as early as 12 d after the lesion, as well as in animals as old as 118 d. Immunochemical staining for the calcium binding protein, parvalbumin, shows a decrease in neuronal and neuropil staining within the microgyrus. These findings suggest that inhibition might be decreased within the lesion, which may contribute to generation of the adjacent hyperexcitable region. These results demonstrate that this animal model is appropriate for examining the mechanisms contributing to epileptogenesis associated with a cortical malformation.}, Author = {Jacobs, K. M. and Gutnick, M. J. and Prince, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Cerebral Cortex;Epilepsy;21 Epilepsy;Research Support, Non-U.S. Gov't;21 Dysplasia-heterotopia;21 Neurophysiology;Rats;Immunohistochemistry;Models, Neurological;Research Support, U.S. Gov't, P.H.S.;In Vitro;Animals, Newborn;Electrophysiology;Animals;24 Pubmed search results 2008;Freezing;Membrane Potentials}, Medline = {96324305}, Nlm_Id = {9110718}, Number = {3}, Organization = {Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA 94305, USA.}, Pages = {514-23}, Pubmed = {8670677}, Title = {Hyperexcitability in a model of cortical maldevelopment}, Uuid = {391A21C2-013D-11DB-9E68-000D9346EC2A}, Volume = {6}, Year = {1996}} @article{Jacobs:1999, Abstract = {The presence of developmental cortical malformations is associated with epileptogenesis and other neurological disorders. In recent years, animal models specific to certain malformations have been developed to study the underlying epileptogenic mechanisms. Teratogens (chemical, thermal or radiation) applied during cortical neuroblast division and migration result in lissencephaly and focal cortical dysplasia. Animals with these malformations have a lowered seizure threshold as well as histopathologies typical of those found in human dysgenic brains. Alterations that may promote epileptogenesis have been identified in lissencephalic brains, such as increased numbers of bursting types of neurons, and abnormal connections between hippocampus, subcortical heterotopia, and neocortex. A distinct set of pathological properties is present in animal models of 4-layered microgyria, induced with cortical lesions made during late stages of cortical neuroblast migration. Hyperexcitability has been demonstrated in cortex adjacent to the microgyrus (paramicrogyral zone) in in vitro slice preparations. A number of observations suggest that cellular differentiation is delayed in microgyric brains. Other studies show increases in postsynaptic glutamate receptors and decreases in GABA(A) receptors in microgyric cortex. These alterations could promote epileptogenesis, depending on which cell types have the altered receptors. The microgyrus lacks thalamic afferents from sensory relay nuclei, that instead appear to project to the paramicrogyral region, thereby increasing excitatory connectivity within this epileptogenic zone. These studies have provided a necessary first step in understanding molecular and cellular mechanisms of epileptogenesis associated with cortical malformations.}, Author = {Jacobs, K. M. and Kharazia, V. N. and Prince, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:48 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Epilepsy;Cerebral Cortex;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;21 Dysplasia-heterotopia;21 Neurophysiology;21 Epilepsy;Research Support, U.S. Gov't, P.H.S.;Methylazoxymethanol Acetate;Abnormalities, Drug-Induced;Synaptic Transmission;Disease Models, Animal;Nucleic Acid Synthesis Inhibitors;Animals;review;Humans}, Medline = {99443187}, Month = {9}, Nlm_Id = {8703089}, Number = {2-3}, Organization = {Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA 94305, USA.}, Pages = {165-88}, Pubmed = {10515164}, Title = {Mechanisms underlying epileptogenesis in cortical malformations}, Uuid = {468A60D5-D911-4990-A14E-7FF940061AF3}, Volume = {36}, Year = {1999}, url = {papers/Jacobs_EpilepsyRes1999.pdf}} @article{Jacobs:1999a, Abstract = {Polymicrogyria, a developmental cortical malformation associated with epilepsy, can be modeled in rats with a transcortical freeze lesion on the day of birth (P0) or P1. We have used field potential recordings to characterize the incidence, propagation patterns, and distribution of epileptiform activity in slices from rats with experimental microgyri. Interictal-like epileptiform activity was evoked in slices from 85\%of freeze-lesioned rats aged P12-P118. These data show age-specific properties of epileptogenesis, including: a delay in onset, a decrease in the incidence of epileptiform activity in rats >P40 that was specific to those lesioned on P0 as opposed to P1, and a shift in the likely site of initiation to areas further from the microgyrus in mature animals. Several observations suggest that the area adjacent to the microgyrus, which appears histologically normal in Nissl stains, contains the necessary epileptogenic neuronal circuits: 1) in 78\%of slices, epileptiform activity could be evoked only from a focal zone adjacent to the microgyrus (paramicrogyral zone) and not within the microgyrus proper; 2) epileptiform activity consistently originated from a particular site within this paramicrogyral zone, independent of the location of the stimulating electrode, suggesting that the generator is outside of the microgyrus; 3) evoked epileptiform activities in the paramicrogyral cortex were unaltered after separation of this zone from the microgyrus with a transcortical cut; and 4) the short-latency graded field potential evoked in the paramicrogyral zone contained an additional negativity not seen in control slices. The epileptiform activity was blocked reversibly by N-methyl--aspartate receptor antagonists in slices from mature as well as immature freeze-lesioned rats. These results suggest that aberrant synaptic connectivity develops in rat cortex surrounding the microgyrus and produces a focal epileptogenic zone whose capacity to generate epileptiform activities does not depend on connections with the malformation itself. We hypothesize that afferents, originating from cortical and extracortical sites, lose their targets in the region of the malformation and make appropriate laminar contacts in the cortex adjacent to the malformation, creating an overabundance of excitatory input to this cortical zone. Increased excitatory feedback onto specific cortical elements may be one factor involved in epileptogenesis in this model of a cortical malformation.}, Author = {Jacobs, K. M. and Hwang, B. J. and Prince, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:48 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Aging;Survival;Epilepsies, Partial;Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Research Support, U.S. Gov't, P.H.S.;Models, Neurological;Electrodes;In Vitro;Evoked Potentials, Motor;Receptors, N-Methyl-D-Aspartate;Animals;24 Pubmed search results 2008;Cerebral Cortex;21 Epilepsy}, Medline = {99115794}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California 94305, USA.}, Pages = {159-73}, Pubmed = {9914277}, Title = {Focal epileptogenesis in a rat model of polymicrogyria}, Uuid = {431C8833-013D-11DB-9E68-000D9346EC2A}, Volume = {81}, Year = {1999}, url = {papers/Jacobs_JNeurophysiol1999.pdf}} @article{Jacobs:2007, Abstract = {A growing body of animal research suggests that neurons represent information not only in terms of their firing rates but also by varying the timing of spikes relative to neuronal oscillations. Although researchers have argued that this temporal coding is critical in human memory and perception, no supporting data from humans have been reported. This study provides the first analysis of the temporal relationship between brain oscillations and single-neuron activity in humans. Recording from 1924 neurons, we find that neuronal activity in various brain regions increases at specific phases of brain oscillations. Neurons in widespread brain regions were phase locked to oscillations in the theta- (4-8 Hz) and gamma- (30-90 Hz) frequency bands. In hippocampus, phase locking was prevalent in the delta- (1-4 Hz) and gamma-frequency bands. Individual neurons were phase locked to various phases of theta and delta oscillations, but they only were active at the trough of gamma oscillations. These findings provide support for the temporal-coding hypothesis in humans. Specifically, they indicate that theta and delta oscillations facilitate phase coding and that gamma oscillations help to decode combinations of simultaneously active neurons.}, Author = {Jacobs, Joshua and Kahana, Michael J. and Ekstrom, Arne D. and Fried, Itzhak}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;21 Cortical oscillations;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Neuroscience Graduate Group, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.}, Pages = {3839-44}, Pii = {27/14/3839}, Pubmed = {17409248}, Title = {Brain oscillations control timing of single-neuron activity in humans}, Uuid = {91F0D7E3-ADD6-470D-A77F-68B5295186A3}, Volume = {27}, Year = {2007}, url = {papers/Jacobs_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4636-06.2007}} @article{Jacobs:2000, Abstract = {Neurogenesis (the birth of new neurons) continues postnatally and into adulthood in the brains of many animal species, including humans. This is particularly prominent in the dentate gyrus of the hippocampal formation. One of the factors that potently suppresses adult neurogenesis is stress, probably due to increased glucocorticoid release. Complementing this, we have recently found that increasing brain levels of serotonin enhance the basal rate of dentate gyrus neurogenesis. These and other data have led us to propose the following theory regarding clinical depression. Stress-induced decreases in dentate gyrus neurogenesis are an important causal factor in precipitating episodes of depression. Reciprocally, therapeutic interventions for depression that increase serotonergic neurotransmission act at least in part by augmenting dentate gyrus neurogenesis and thereby promoting recovery from depression. Thus, we hypothesize that the waning and waxing of neurogenesis in the hippocampal formation are important causal factors, respectively, in the precipitation of, and recovery from, episodes of clinical depression.}, Author = {Jacobs, B. L. and Praag, H. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Mol Psychiatry}, Keywords = {Stress, Psychological/pathology/physiopathology;01 Adult neurogenesis general;Adult;Brain/*pathology/*physiopathology;Human;Models, Neurological;A abstr;Models, Psychological;Depressive Disorder/pathology/*physiopathology;Depression/pathology/*physiopathology;Animal;Support, U.S. Gov't, P.H.S.;Neurons/*pathology/*physiology;Support, Non-U.S. Gov't}, Number = {3}, Organization = {Program in Neuroscience, Princeton University, Princeton, NJ 08544- 1010, USA. barryj\@princeton.edu}, Pages = {262-9.}, Title = {Adult brain neurogenesis and psychiatry: a novel theory of depression}, Uuid = {40C8063E-5751-4D60-AB3F-09BD585E3DC7}, Volume = {5}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10889528}} @article{Jacobs:2006, Abstract = {Retinoic acid (RA) is commonly used in vitro to differentiate stem cell populations including adult neural stem cells into neurons; however, the in vivo function of RA during adult neurogenesis remains largely unexplored. We found that depletion of RA in adult mice leads to significantly decreased neuronal differentiation within the granular cell layer of the dentate gyrus. RA contribution to neurogenesis occurs early, for RA deficiency also results in a decrease in newborn cells expressing an immature neuronal marker. Furthermore, although proliferation is unaffected during RA absence, cell survival is significantly reduced. Finally, a screen for retinoid-induced genes identifies metabolic targets including the lipid transporters, CD-36 and ABCA-1, the lipogenic master regulator SREBP1c as well as components of the Wnt signaling pathway. Our results reveal RA as a crucial contributor to early stages of adult neurogenesis and survival in vivo.}, Author = {Jacobs, Sharoni and Lie, D. Chichung and DeCicco, Kathleen L. and Shi, Yanhong and DeLuca, Luigi M. and Gage, Fred H. and Evans, Ronald M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7505876}, Number = {10}, Organization = {Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.}, Pages = {3902-7}, Pii = {0511294103}, Pubmed = {16505366}, Title = {Retinoic acid is required early during adult neurogenesis in the dentate gyrus}, Uuid = {C6990B18-A61C-40F9-91A6-0BD3D40156A8}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0511294103}} @article{Jadhav:2006, Abstract = {Signaling through the Notch pathway regulates multiple aspects of development. The vertebrate retina allows an investigation of the basis for these various effects, because the major cell types of the retina arise from a common progenitor that expresses Notch1. The Notch pathway was constitutively activated in distinct populations of retinal cells during development. Prolonged Notch activity in progenitor cells maintained cells in the progenitor state without perturbing temporal identity, promoting early progenitor characteristics early in development and late progenitor characteristics later in development. Eventually, constitutive Notch activation led these cells to acquire characteristics of glial and stem cells. In contrast, reactivating the Notch pathway in newly postmitotic retinal cells promoted mature glial cell formation in a subset of cells. These data suggest that prolonged Notch activity does not disrupt the normal progression of progenitor temporal states, and that down-regulating or overcoming Notch activity is required for proper formation of both neuronal and glial cell fates.}, Author = {Jadhav, Ashutosh P. and Cho, Seo-Hee H. and Cepko, Constance L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {7505876}, Number = {50}, Organization = {Division of Health Sciences and Technology, Department of Genetics, Harvard-Massachusetts Institute of Technology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.}, Pages = {18998-9003}, Pii = {0608155103}, Pubmed = {17148603}, Title = {Notch activity permits retinal cells to progress through multiple progenitor states and acquire a stem cell property}, Uuid = {19FCC327-AAED-4C04-B881-12FB89A8138D}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0608155103}} @article{Jaeger:2004, Abstract = {We present a method for learning nonlinear systems, echo state networks (ESNs). ESNs employ artificial recurrent neural networks in a way that has recently been proposed independently as a learning mechanism in biological brains. The learning method is computationally efficient and easy to use. On a benchmark task of predicting a chaotic time series, accuracy is improved by a factor of 2400 over previous techniques. The potential for engineering applications is illustrated by equalizing a communication channel, where the signal error rate is improved by two orders of magnitude.}, Author = {Jaeger, Herbert and Haas, Harald}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {20 Networks;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {0404511}, Number = {5667}, Organization = {International University Bremen, Bremen D-28759, Germany. h.jaeger\@iu-bremen.de}, Pages = {78-80}, Pii = {304/5667/78}, Pubmed = {15064413}, Title = {Harnessing nonlinearity: predicting chaotic systems and saving energy in wireless communication}, Uuid = {04119B0A-FE4F-4C0C-BA5D-6742DBCA7E8E}, Volume = {304}, Year = {2004}, url = {papers/Jaeger_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1091277}} @article{Jaenisch:1983, Author = {Jaenisch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {15 ERVs retroelements;Genes, Viral;Gene Expression Regulation;Retroviridae;15 Retrovirus mechanism;DNA Transposable Elements;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0413066}, Number = {1}, Pages = {5-6}, Pii = {0092-8674(83)90491-9}, Pubmed = {6297787}, Title = {Endogenous retroviruses}, Uuid = {AB21159F-769B-4DF5-BBD3-63ABC3923134}, Volume = {32}, Year = {1983}, url = {papers/Jaenisch_Cell1983.pdf}} @article{Jakubs:2006, Abstract = {Neural progenitors in the adult dentate gyrus continuously produce new functional granule cells. Here we used whole-cell patch-clamp recordings to explore whether a pathological environment influences synaptic properties of new granule cells labeled with a GFP-retroviral vector. Rats were exposed to a physiological stimulus, i.e., running, or a brain insult, i.e., status epilepticus, which gave rise to neuronal death, inflammation, and chronic seizures. Granule cells formed after these stimuli exhibited similar intrinsic membrane properties. However, the new neurons born into the pathological environment differed with respect to synaptic drive and short-term plasticity of both excitatory and inhibitory afferents. The new granule cells formed in the epileptic brain exhibited functional connectivity consistent with reduced excitability. We demonstrate a high degree of plasticity in synaptic inputs to adult-born new neurons, which could act to mitigate pathological brain function.}, Author = {Jakubs, and Nanobashvili, and Bonde, and Ekdahl, and Kokaia, and Kokaia, and Lindvall,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Laboratory of Neurogenesis and Cell Therapy, Section of Restorative Neurology, Wallenberg Neuroscience Center, University Hospital, SE-221 84 Lund, Sweden; Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Biomedical Center, SE-221 84 Lund, Sweden.}, Pages = {1047-1059}, Pii = {S0896-6273(06)00870-1}, Pubmed = {17178407}, Title = {Environment Matters: Synaptic Properties of Neurons Born in the Epileptic Adult Brain Develop to Reduce Excitability}, Uuid = {745F4500-441F-4914-BEDB-87E73A41A60F}, Volume = {52}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.11.004}} @article{Jang:2004, Abstract = {Both plasticity and cell fusion have been suggested to have a role in germ-layer switching. To understand the mechanisms underlying cell fate changes, we have examined a highly enriched population of hematopoietic stem cells (HSCs) in vitro or in vivo in response to injury for liver-specific phenotypic and functional changes. Here we show that HSCs become liver cells when cocultured with injured liver separated by a barrier. Chromosomal analyses and tissue-specific gene and/or protein expression show that microenvironmental cues rather than fusion are responsible for conversion in vitro. We transplanted HSCs into liver-injured mice and observed that HSCs convert into viable hepatocytes with increasing injury. Notably, liver function was restored 2-7 d after transplantation. We conclude that HSCs contribute to the regeneration of injured liver by converting into functional hepatocytes without fusion. 1465-7392 Journal Article}, Author = {Jang, Y. Y. and Collector, M. I. and Baylin, S. B. and Diehl, A. M. and Sharkis, S. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {Nat Cell Biol}, Keywords = {EE pdf;08 Aberrant cell cycle}, Number = {6}, Organization = {Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.}, Pages = {532-9}, Title = {Hematopoietic stem cells convert into liver cells within days without fusion}, Uuid = {F63C7309-6092-418C-95B3-16A4A6922502}, Volume = {6}, Year = {2004}, url = {papers/Jang_NatCellBiol2004.pdf}} @article{Jankovski:1998, Abstract = {The subventricular zone of the adult mammalian forebrain contains progenitor cells that, by migrating along a restricted pathway called the 'rostral migratory stream'(RMS), add new neurons to the olfactory bulb throughout life. To determine the influence of the olfactory bulb on the development of these progenitor cells, we performed lesions that interrupt this pathway and separate the olfactory bulb from the rest of the forebrain. By labelling cells born at several survival times after the lesions with the thymidine analogue bromodeoxyuridine (BrdU), we found that disconnection from the bulb influences the rate of BrdU incorporation by the progenitor cells. The number of labelled cells in lesioned mice was almost half that found in control mice. In the disconnected migratory pathway, the number of neurons expressing calretinin was increased indicating that neuronal differentiation was enhanced: newly born neurons occurred within and around the RMS, most of them expressed calretinin and left the pathway starting about 2 weeks after the lesion. Thereafter, these neurons preserving their phenotype, spread for long distances, and accumulated ectopically in dorsal regions of the anterior olfactory nucleus and the frontal cortex. Finally, transplantation of adult subventricular cells into the lesioned pathway showed that the lesion neither prevents neuronal migration nor alters its direction. Thus, although the olfactory bulb appears to regulate the pace of the developmental processes, its disconnection does not prevent the proliferation, migration and phenotypic acquisition of newly generated bulbar interneurons that, since they cannot reach their terminal domains, populate some precise regions of the lesioned adult forebrain.}, Author = {Jankovski, A. and Garcia, C. and Soriano, E. and Sotelo, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Eur J Neurosci}, Keywords = {Cell Movement/*physiology;Stem Cells/chemistry/*cytology;Animal;Cell Count;02 Adult neurogenesis migration;Mice, Transgenic;Nerve Tissue Proteins/analysis;Bromodeoxyuridine/analysis;B-8;Cell Survival/physiology;Prosencephalon/cytology/growth &development/surgery;Calcium-Binding Protein, Vitamin D-Dependent/analysis;Support, Non-U.S. Gov't;Cell Division/physiology;Olfactory Bulb/*cytology/growth &development/*surgery;Age Factors;Mice;Cell Differentiation/physiology;Antimetabolites/analysis;Interneurons/chemistry/*cytology}, Number = {12}, Organization = {INSERM U-106, Paris, France.}, Pages = {3853-68.}, Title = {Proliferation, migration and differentiation of neuronal progenitor cells in the adult mouse subventricular zone surgically separated from its olfactory bulb}, Uuid = {D736DC0B-48B1-4E33-AC7B-C71CA9465511}, Volume = {10}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9875362}} @article{Jankovski:1996, Abstract = {To gain insight into cellular and molecular mechanisms subserving neuronal cell migration in the adult mouse forebrain, we have first investigated the cellular composition of the subventricular zone- olfactory bulb pathway (SVZ-OB). The pathway was essentially composed of cells with neuronal and astrocytic identities, neuronal cells being four times more numerous than astrocytes. Neuronal cells (precursors and some young postmitotic neurons) formed continuous cellular strands of migratory cells from the anterior horn of the lateral ventricle to the olfactory bulb. These chains of migrating cells moved within channels formed by the processes of a special subpopulation of astrocytes. The neuronal cells expressed the embryonic form of polysialic acid neural cell adhesion molecule, and the astrocytes were tenascin-C positive, thus preserving an embryonic cellular environment. Through transplantation experiments, the second part of this study attempted to analyze the functional properties of the adult SVZ-OB pathway. Early postnatal (P2-13) cerebellar progenitor cells, taken from a transgenic mouse line in which cerebellar granule cells and molecular layer interneurons (basket/stellate cells) expressed the reporter gene lacZ, were implanted in the SVZ-OB pathway of adult wild- type mice. Unlike grafted SVZ cells that migrate all along the pathway, none of the cerebellar precursors reached the olfactory bulb, although some of them were able to migrate along the caudal one-third of the pathway. The majority (over 67\%) of the migrating cells were progenitors that acquired the phenotype of basket/stellate cells. Granule cell progenitors and most granule cells did not survive transplantation. These results show that the adult SVZ-OB pathway is not a "passive generic guidance"for all classes of premigratory neurons. From the two types of grafted cerebellar progenitors, only those with migratory capability and that do not follow radial glial axes are able to translocate along the SVZ-OB pathway. Furthermore, the basket/stellate cell progenitors are specified at the time of grafting: Neither their identity nor the pace of expression of their major distinctive features are influenced by local signals emanating from the adult forebrain.}, Author = {Jankovski, A. and Sotelo, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Comp Neurol}, Keywords = {Stem Cells/*transplantation;02 Adult neurogenesis migration;Cerebellum/cytology/*transplantation;B;Lac Operon;Microscopy, Electron;Neural Pathways/physiology;Animal;Neurons/*cytology;Mice, Transgenic;Olfactory Bulb/*physiology;Astrocytes/*cytology;Prosencephalon/*physiology;Mice;Neuroglia/cytology;*Transplantation, Heterotopic;Cell Movement/physiology}, Number = {3}, Organization = {INSERM U. 106, Hopital de la Salpetriere, Paris, France.}, Pages = {376-96.}, Title = {Subventricular zone-olfactory bulb migratory pathway in the adult mouse: cellular composition and specificity as determined by heterochronic and heterotopic transplantation}, Uuid = {87D1F70B-B1AD-4361-BDD7-77AFF7DC5E10}, Volume = {371}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8842894}} @article{Janusonis:2004, Abstract = {Although the serotonergic system plays an important role in various neurological disorders, the role of early serotonergic projections to the developing cerebral cortex is not well understood. Because serotonergic fibers enter the marginal zone (MZ) before birth, it has been suggested that they may influence cortical development through synaptic contacts with Cajal-Retzius (CR) cells. We used immunohistochemistry combined with confocal and electron microscopy to show that the earliest serotonergic projections to the MZ form synaptic contacts with the somata and proximal dendrites of CR cells as early as embryonic day 17. To elucidate the functional significance of these early serotonergic contacts with CR cells, we perturbed their normal development by injecting pregnant mice with 5-methoxytryptamine. Lower reelin levels were detected in the brains of newborn pups from the exposed animals. Because reelin plays an important role in the cortical laminar and columnar organization during development, we killed some pups from the same litters on postnatal day 7 and analyzed their presubicular cortex. We found that the supragranular layers of the presubicular cortex (which normally display a visible columnar deployment of neurons) were altered in the treated animals. Our results suggest a mechanism of how serotonergic abnormalities during cortical development may disturb the normal cortical organization; and, therefore, may be relevant for understanding neurological disorders in which abnormalities of the serotonergic system are accompanied by cortical pathology (such as autism).}, Author = {Janusonis, Skirmantas and Gluncic, Vicko and Rakic, Pasko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;5-Methoxytryptamine;Animals;Pregnancy;Synapses;Female;Axons;Cell Adhesion Molecules, Neuronal;Dendrites;Extracellular Matrix Proteins;Support, Non-U.S. Gov't;Nervous System Malformations;Cerebral Cortex;Neurons;Support, U.S. Gov't, P.H.S.;Mice;Prenatal Exposure Delayed Effects;Gestational Age;Serotonin}, Month = {2}, Nlm_Id = {8102140}, Number = {7}, Organization = {Yale University School of Medicine, Department of Neurobiology, New Haven, Connecticut 06520-8001, USA.}, Pages = {1652-9}, Pii = {24/7/1652}, Pubmed = {14973240}, Title = {Early serotonergic projections to Cajal-Retzius cells: relevance for cortical development}, Uuid = {C23436D7-8209-4B2D-A22B-61305596346B}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4651-03.2004}} @article{Jarrosson-Wuilleme:2006, Abstract = {It is commonly accepted that infection of nondividing cells by gammaretroviruses such as the murine leukemia viruses is inefficient due to their inability to cross the nuclear envelope barrier. Challenging this notion, we now show that human nondividing macrophages display a specific window of susceptibility to transduction with a Friend murine leukemia virus (F-MLV)-derived vector during their differentiation from monocytes. This finding suggests that factors other than the nuclear membrane govern permissiveness to gammaretroviral infection and raises the possibility of using the macrophage tropism of F-MLV in gene therapy.}, Author = {Jarrosson-Wuilleme, Loraine and Goujon, Caroline and Bernaud, Jeanine and Rigal, Dominique and Darlix, Jean-Luc L. and Cimarelli, Andrea}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {11 Glia;15 Retrovirus mechanism}, Month = {2}, Nlm_Id = {0113724}, Number = {3}, Organization = {LaboRetro, INSERM U412, Ecole Normale Sup{\'e}rieure de Lyon, IFR 128 BioSciences Lyon-Gerland, 46 All{\'e}e d'Italie, 69364 Lyon, France. acimarel\@ens-lyon.fr.}, Pages = {1152-9}, Pii = {80/3/1152}, Pubmed = {16414992}, Title = {Transduction of nondividing human macrophages with gammaretrovirus-derived vectors}, Uuid = {E2DA51BF-93D6-43B1-9797-CBE1972E3F3D}, Volume = {80}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.80.3.1152-1159.2006}} @article{Jarvis:2001, Abstract = {An important but poorly understood event associated with ischemia is anoxic depolarization (AD), a sudden and profound depolarization of neurons and glia in cortical and subcortical gray matter. Leao first measured the AD as a wave of electrical silence moving across the cerebral cortex in 1947 and noted its similarity to spreading depression (SD). SD is harmless when coursing through normoxic cortical tissue as during migraine aura. However for 3-4 h following focal ischemia, the additional metabolic stress arising from recurring SD in the penumbra expands the ischemic core, so SD blockade is potentially beneficial therapeutically. In the present study, we measured intrinsic optical signals (IOSs) to monitor anoxic depolarization in submerged rat neocortical slices during O2/glucose deprivation (OGD). After approximately 6 min of OGD, the AD was imaged as a focal increase in light transmittance which then propagated across neocortical gray at approximately 2 mm/min. Although the slice was globally stressed, the AD always initiated focally, sometimes at multiple sites. Its propagation was coincident with a transient negative shift in the extracellular potential, the electrical signature of AD. Acute damage to neocortex (measured as a delayed decrease in LT and as a loss of the evoked field potential) followed only where the AD had propagated, so it is the combined metabolic demands of AD and OGD that acutely damages all layers of the neocortex. Glutamate receptor antagonists (2 mM kynurenate or 25 microM AP-5/10 microM CNQX) did not block AD initiation, slow its propagation or prevent post-AD damage. This study shows that acute ischemic damage is greatly exacerberated by AD during metabolic stress and that glutamate receptor antagonists are not protective. Using this slice model, therapeutically tolerable drugs that block the AD and SD can be investigated.}, Author = {Jarvis, C. R. and Anderson, T. R. and Andrew, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Excitatory Amino Acid Antagonists;Receptors, Glutamate;Animals;Rats;Glutamic Acid;Neocortex;Excitatory Amino Acid Agonists;Rats, Sprague-Dawley;Anoxia;Male;research support, non-u.s. gov't ;Action Potentials;N-Methylaspartate;21 Neurophysiology;Brain Ischemia;Neurons;6-Cyano-7-nitroquinoxaline-2,3-dione;Spreading Cortical Depression;24 Pubmed search results 2008;Kynurenic Acid}, Month = {3}, Nlm_Id = {9110718}, Number = {3}, Organization = {Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada K7L 3N6.}, Pages = {249-59}, Pubmed = {11230096}, Title = {Anoxic depolarization mediates acute damage independent of glutamate in neocortical brain slices}, Uuid = {957F713F-B489-4789-983B-CB40A8CDF10A}, Volume = {11}, Year = {2001}} @article{Jessell:2000, Abstract = {Our understanding of neural development has advanced dramatically over the past decade. Significant insights have now been obtained into seven fundamental developmental processes: first, induction of the neural plate; second, regionalization of the neural tube along the dorsoventral and anteroposterior axes; third, generation of neurons and glia from multipotential precursors; fourth, apoptotic cell death; fifth, migration of neurons; sixth, guidance of axons to their targets; and seventh, formation of synapses.}, Author = {Jessell, T. M. and Sanes, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {21 Neurophysiology;Animals;Brain;24 Pubmed search results 2008;review;Humans}, Month = {10}, Nlm_Id = {9111376}, Number = {5}, Organization = {Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, 701 West 168th Street, NY, New York 10032, USA. tmj1\@columbia.edu}, Pages = {599-611}, Pii = {S0959-4388(00)00136-7}, Pubmed = {11084323}, Title = {Development. The decade of the developing brain}, Uuid = {642159B2-8BF7-4EC8-99C0-6E52B126CAA7}, Volume = {10}, Year = {2000}} @article{Ji:2007, Abstract = {Sleep replay of awake experience in the cortex and hippocampus has been proposed to be involved in memory consolidation. However, whether temporally structured replay occurs in the cortex and whether the replay events in the two areas are related are unknown. Here we studied multicell spiking patterns in both the visual cortex and hippocampus during slow-wave sleep in rats. We found that spiking patterns not only in the cortex but also in the hippocampus were organized into frames, defined as periods of stepwise increase in neuronal population activity. The multicell firing sequences evoked by awake experience were replayed during these frames in both regions. Furthermore, replay events in the sensory cortex and hippocampus were coordinated to reflect the same experience. These results imply simultaneous reactivation of coherent memory traces in the cortex and hippocampus during sleep that may contribute to or reflect the result of the memory consolidation process.}, Author = {Ji, Daoyun and Wilson, Matthew A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Rats, Long-Evans;Animals;Rats;Memory;Cell Count;Hippocampus;research support, non-u.s. gov't;Behavior, Animal;Sleep;Statistics;Action Potentials;Electromyography;21 Neurophysiology;Neurons;research support, n.i.h., extramural;Probability;24 Pubmed search results 2008;Visual Cortex;Electroencephalography}, Month = {1}, Nlm_Id = {9809671}, Number = {1}, Organization = {The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. dji\@mit.edu}, Pages = {100-7}, Pii = {nn1825}, Pubmed = {17173043}, Title = {Coordinated memory replay in the visual cortex and hippocampus during sleep}, Uuid = {C5756DE4-2657-4B3B-8B67-8051C5DE4528}, Volume = {10}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1825}} @article{Jiang:2004, Abstract = {Vectors suitable for delivery of therapeutic genes to the CNS for chronic neurodegenerative diseases will require regulatable transgene expression. In this study, three self-regulating rAAV vectors encoding humanized green fluorescent protein (hGFP) were made using the tetracycline (tet)-off system. Elements were cloned in different orientations relative to each other and to the AAV internal terminal repeat (ITRs). The advantage of this vector system is that all infected cells will carry both the 'therapeutic' gene and the tet-regulator. To compare the efficiency of the vectors, 293T cells infected by each vector were grown in the presence or absence of the tet-analog doxycycline (dox). Cells were analyzed by flow cytometry for hGFP protein expression, and quantitative RT-PCR (QRT-PCR) for levels of hGFP mRNA and the tet-activator (tTA) mRNA. In the presence of dox, cells infected with one of the vectors, rAAVS3, showed less than 2\%total fluorescent intensity and mRNA copy number than cells grown without dox. The other two vectors were significantly more leaky. Levels of tTA mRNA were not affected by dox. The S3 vector also displayed tight regulation in HeLa and HT1080 cells. To assess regulation in the brain, the S3 vector was injected into rat striatum and rats maintained on regular or dox-supplemented water. At 1 month after vector injection, numerous positive cells were observed in rats maintained on regular water whereas only rare positive cells with very low levels of fluorescence were observed in rats maintained on water containing dox. The QRT-PCR analysis showed that dox inhibited expression of hGFP mRNA in brain by greater than 99\%. These results demonstrate that exceedingly tight regulation of transgene expression is possible using the tet-off system in the context of a self-regulating rAAV vector and that the specific orientation of two promoters relative to each other and to the ITRs is important. Regulatable vectors based on this design are ideal for therapeutic gene delivery to the CNS.}, Author = {Jiang, L. and Rampalli, S. and George, D. and Press, C. and Bremer, E. G. and O'Gorman, M. R. G. and Bohn, M. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Gene Expression Regulation;Humans;Rats;Tetracycline;Dependovirus;Recombinant Proteins;RNA, Messenger;11 Glia;Green Fluorescent Proteins;Hela Cells;Reverse Transcriptase Polymerase Chain Reaction;Genetic Vectors;Cell Line;Rats, Inbred F344;Research Support, U.S. Gov't, P.H.S.;Gene Therapy;Flow Cytometry;Neurodegenerative Diseases;Doxycycline;Luminescent Proteins;Central Nervous System;Gene Expression;Transgenes}, Month = {7}, Nlm_Id = {9421525}, Number = {13}, Organization = {1Department of Pediatrics, Children's Memorial Institute for Education &Research, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.}, Pages = {1057-67}, Pii = {3302245}, Pubmed = {15152187}, Title = {Tight regulation from a single tet-off rAAV vector as demonstrated by flow cytometry and quantitative, real-time PCR}, Uuid = {BBB661F9-369A-473B-8FB8-0612CD24E4B7}, Volume = {11}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3302245}} @article{Jiang:1998, Abstract = {In the adult songbird forebrain, neurons continue to be produced from precursor cells in the forebrain ependymal/subependymal zone (SZ), from which they migrate upon radial guide fibers. The new neurons and their radial cell partners may coderive from a common SZ progenitor, which may be the radial cell itself. On this basis, we asked whether radial cells might provide trophic support for the migration or survival of newly generated neurons. We focused upon the insulin-like growth factors (IGFs) IGF-1 and IGF-2, which have previously been shown to support the survival and differentiation of neural progenitor cells. We found that IGF-1 immunoreactivity was expressed heavily by adult zebra finch radial cells and their fibers, with little expression otherwise. IGF-2, in contrast, was expressed by parenchymal astrocytes and exhibited little radial cell expression. Despite their distinct distributions, IGF-1 and IGF-2 exerted similar trophic effects on finch SZ cells in vitro; both greatly increased the number of neurons migrating from explants of the adult finch SZ, relative to explants raised in low-insulin, IGF-1-deficient media. However, neither factor extended neuronal survival. These results suggest that in neurogenic regions of the adult avian forebrain, IGF-1 acts as a radial cell- associated neuronal differentiation and/or departure factor, which may serve to regulate neuronal recruitment into the adult brain.}, Author = {Jiang, J. and McMurtry, J. and Niedzwiecki, D. and Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurobiol}, Keywords = {Nerve Growth Factors/*physiology;Ependyma/cytology/*physiology;Neurons/*physiology;C;Female;Corpus Striatum/cytology/metabolism/*physiology;Insulin-Like Growth Factor I/*physiology;Animal;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Astrocytes/metabolism;Vocalization, Animal/physiology;04 Adult neurogenesis factors;Insulin-Like Growth Factor II/metabolism;Birds/*physiology;Cell Movement/physiology}, Number = {1}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York, New York 10021, USA.}, Pages = {1-15.}, Title = {Insulin-like growth factor-1 is a radial cell-associated neurotrophin that promotes neuronal recruitment from the adult songbird edpendyma/subependyma}, Uuid = {D422B255-D4C6-420E-A97C-76C25AC8EC22}, Volume = {36}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9658334}} @article{Jiang:1998a, Abstract = {Chemokines are a group of pro-inflammatory peptides that mediate leukocyte migration and activation. Several members of the chemokine family have been shown to be synthesized by cells of the central nervous system (CNS). To begin to address the role of chemokine receptors in CNS physiology, we identified, by molecular cloning techniques, the rat orthologs of the chemokine receptors, CCR2, CCR3, CCR5, and CXCR4. CCR2 and CCR5 expression was detected in rat spleen, lung, kidney, thymus and macrophages; CCR5 mRNA was also detected in rat brain. Primary cultures of rat microglia expressed CCR5 mRNA that was regulated by IFN-gamma, while both cultured astrocytes and microglia were found to contain mRNA for CXCR4 and CX3CR1. Induction of experimental allergic encephalomyelitis (EAE) in the rat was accompanied by increased levels of CCR2, CCR5, CXCR4, and CX3CR1 mRNAs in the lumbar spinal cords of animals displaying clinical signs of the disease. These data identify the rat orthologs of chemokine receptors and demonstrate that brain, spinal cord, and cultured glial cells express chemokine receptors that can be regulated both in vitro and in vivo.}, Author = {Jiang, Y. and Salafranca, M. N. and Adhikari, S. and Xia, Y. and Feng, L. and Sonntag, M. K. and deFiebre, C. M. and Pennell, N. A. and Streit, W. J. and Harrison, J. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Human;Rats, Inbred Lew;GTP-Binding Proteins;Astrocytes;Gene Expression Regulation;Kidney;Rats;Cells, Cultured;Animals;Cloning, Molecular;Encephalomyelitis, Experimental Autoimmune;Microglia;Rats, Sprague-Dawley;RNA, Messenger;Not relevant;11 Glia;Male;Spinal Cord;Xenopus laevis;Support, Non-U.S. Gov't;Brain Chemistry;Receptors, Chemokine;Support, U.S. Gov't, P.H.S.;Amino Acid Sequence;Molecular Sequence Data}, Medline = {98318173}, Month = {6}, Nlm_Id = {8109498}, Number = {1}, Organization = {Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville 32610-0267, USA.}, Pages = {1-12}, Pii = {S0165572898000058}, Pubmed = {9655467}, Title = {Chemokine receptor expression in cultured glia and rat experimental allergic encephalomyelitis}, Uuid = {3C442BDA-F2F7-4DCA-B025-D24B818306F7}, Volume = {86}, Year = {1998}} @article{Jiang:2005, Abstract = {Apoptosis is an essential process during normal neuronal development. Approximately one-half of the neurons produced during neurogenesis die before completion of CNS maturation. To characterize the role of the inhibitor of apoptosis gene, survivin, during neurogenesis, we used the Cre-loxP-system to generate mice lacking survivin in neuronal precursor cells. Conditional deletion of survivin starting at embryonic day 10.5 leads to massive apoptosis of neuronal precursor cells in the CNS. Conditional mutants were born at the expected Mendelian ratios; however, these died shortly after birth from respiratory insufficiency, without primary cardiopulmonary pathology. Newborn conditional mutants showed a marked reduction in the size of the brain associated with severe, mutifocal apoptosis in the cerebrum, cerebellum, brainstem, spinal cord, and retina. Caspase-3 and caspase-9 activities in the mutant brains were significantly elevated, whereas bax expression was unchanged from controls. These results show that survivin is critically required for the survival of developing CNS neurons, and may impact on our understanding of neural repair, neural development, and neurodegenerative diseases. Our study is the first to solidify a role for survivin as an antiapoptotic protein during normal neuronal development in vivo.}, Author = {Jiang, Yuying and de Bruin, Alain and Caldas, Hugo and Fangusaro, Jason and Hayes, John and Conway, Edward M. and Robinson, Michael L. and Altura, Rachel A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Retina;Microtubule-Associated Proteins;10 Development;Animals;Pregnancy;Mice, Mutant Strains;Phenotype;Brain;Apoptosis;Female;Integrases;Gene Deletion;08 Aberrant cell cycle;Male;Research Support, U.S. Gov't, P.H.S.;Neurons;Intermediate Filament Proteins;Mice;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {8102140}, Number = {30}, Organization = {Center for Childhood Cancer, Columbus Children's Research Institute, Columbus, Ohio 43205, USA.}, Pages = {6962-70}, Pii = {25/30/6962}, Pubmed = {16049172}, Title = {Essential role for survivin in early brain development}, Uuid = {D46AB62D-22DF-44D9-8ECB-1390B9A67FB1}, Volume = {25}, Year = {2005}, url = {papers/Jiang_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1446-05.2005}} @article{Jiang:1999, Abstract = {Ciliary neurotrophic factor (CNTF) is produced and released in response to injury in the central nervous system (CNS). While CNTF initially was characterized as a trophic factor for neurons, more recent evidence supports roles for this factor in survival, proliferation, and maturation of oligodendrocyte lineage cells. Evidence is emerging to support the hypothesis that CNTF's actions may include enhancing other growth and trophic factors. Here we tested the hypothesis that CNTF can induce expression of receptors on oligodendrocytes for factors that are known to promote their generation, maturation, and survival. Specifically, we used an in vivo paradigm to test whether CNTF, when injected stereotactically into forebrain white matter of adult rats, could induce mRNA expression for the insulin-like growth factor (IGF) type I receptor (IGF-IR), fibroblast growth factor (FGF) receptor (FGFR)-1, FGFR3, and platelet-derived growth factor (PDGF) receptor- alpha (PDGFRalpha). We determined that CNTF injection increased expression of IGF-IR and FGFR1 mRNAs in adult white matter to 200-250\%of control levels. Cellular analysis indicated that these receptor mRNAs were induced in interfascicular oligodendrocytes. In contrast, CNTF had no effect on levels of FGFR3 and PDGFRalpha mRNAs. These results suggest that CNTF enhances the sensitivity of oligodendrocytes to other mitogens and trophic factors via induction of their receptors.}, Author = {Jiang, F. and Levison, S. W. and Wood, T. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci Res}, Keywords = {G;RNA, Messenger/*biosynthesis;Ciliary Neurotrophic Factor;Nerve Growth Factors/*pharmacology;Brain/*drug effects/metabolism;Cell Survival/drug effects;Receptors, Fibroblast Growth Factor/genetics;Rats;Oligodendroglia/*drug effects/metabolism;Receptor, IGF Type 1/*genetics;Female;Animal;Rats, Sprague-Dawley;Glial Fibrillary Acidic Protein/analysis;11 Glia;Support, Non-U.S. Gov't;Nerve Tissue Proteins/*pharmacology;Receptors, Platelet-Derived Growth Factor/genetics;Support, U.S. Gov't, P.H.S.}, Number = {4}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA.}, Pages = {447-57.}, Title = {Ciliary neurotrophic factor induces expression of the IGF type I receptor and FGF receptor 1 mRNAs in adult rat brain oligodendrocytes}, Uuid = {5054657A-B291-423C-BDB2-9B1DD1F7C8B1}, Volume = {57}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10440894}} @article{Jiang:2001, Abstract = {BACKGROUND AND PURPOSE: This study explored the possible occurrence of newly generated nerve cells in the ischemic cortex of adult rats after middle cerebral artery occlusion and reperfusion. METHODS: Nine- to 10-week-old male Wistar rats were subjected to 2 hours of middle cerebral artery occlusion by the monofilament method. Rats received repeated intraperitoneal injections of the cell proliferation-specific marker 5-bromodeoxyuridine (BrdU) after stroke induction. Brain sections were processed for immunohistochemistry with an avidin-biotin complex-alkaline phosphatase and/or -peroxidase method. Brain sections processed with double-immunofluorescent staining were further scanned by confocal microscopy. RESULTS: Interspersed among the predominantly newly formed glial cells, some cells were double labeled by BrdU and 1 of the neuron-specific markers, Map-2, beta-tubulin III, and Neu N, at 30 and 60 days after stroke onset. These cells were randomly distributed throughout cortical layers II through VI, occurring with highest density in the ischemic boundary zone. Three-dimensional confocal analyses of BrdU and the neuron-specific marker Neu N confirmed their colocalization within the same cortical cells. CONCLUSIONS: This study suggests that new neurons can be generated in the cerebral cortex of adult rats after transient focal cerebral ischemia. Cortical neurogenesis may be a potential pathway for brain repair after stroke. 1524-4628 Journal Article}, Author = {Jiang, W. and Gu, W. and Brannstrom, T. and Rosqvist, R. and Wester, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {Stroke}, Keywords = {Disease Models, Animal;Cerebral Cortex/*blood supply/pathology/*physiopathology;Neurons/*cytology/metabolism/pathology;Bromodeoxyuridine/pharmacokinetics;Immunohistochemistry;Rats;D;Cell Division;Cell Count;Rats, Wistar;Infarction, Middle Cerebral Artery/*pathology;Reperfusion;Animals;Support, Non-U.S. Gov't;Male;Neuroglia/cytology/metabolism;*Regeneration}, Number = {5}, Organization = {Departments of Public Health and Clinical Medicine, Medicine, Umea Stroke Center,Umea University (Sweden).}, Pages = {1201-7}, Pubmed = {11340234}, Title = {Cortical neurogenesis in adult rats after transient middle cerebral artery occlusion}, Uuid = {BAA170FE-C26D-11DA-969D-000D9346EC2A}, Volume = {32}, Year = {2001}, url = {papers/Jiang_Stroke2001.pdf}} @article{Jin:2003, Abstract = {Neurogenesis, which may contribute to the ability of the adult brain to function normally and adapt to disease, nevertheless declines with advancing age. Adult neurogenesis can be enhanced by administration of growth factors, but whether the aged brain remains responsive to these factors is unknown. We compared the effects of intracerebroventricular fibroblast growth factor (FGF)-2 and heparin-binding epidermal growth factor-like growth factor (HB-EGF) on neurogenesis in the hippocampal dentate subgranular zone (SGZ) and the subventricular zone (SVZ) of young adult (3-month) and aged (20-month) mice. Neurogenesis, measured by labelling with bromodeoxyuridine (BrdU) and by expression of doublecortin, was reduced by approximately 90\%in SGZ and by approximately 50\%in SVZ of aged mice. HB-EGF increased BrdU labelling in SGZ at 3 months by approximately 60\%and at 20 months by approximately 450\%, which increased the number of BrdU-labelled cells in SGZ of aged mice to approximately 25\%of that in young adults. FGF-2 also stimulated BrdU labelling in SGZ, by approximately 25\%at 3 months and by approximately 250\%at 20 months, increasing the number of newborn neurones in older mice to approximately 20\%of that in younger mice. In SVZ, HB-EGF and FGF-2 increased BrdU incorporation by approximately 140\%at 3 months and approximately 170\%at 20 months, so the number of BrdU-labelled cells was comparable in untreated 3-month-old and growth factor-treated 20-month-old mice. These results demonstrate that the aged brain retains the capacity to respond to exogenous growth factors with increased neurogenesis, which may have implications for the therapeutic potential of neurogenesis enhancement in age-associated neurological disorders. 1474-9718 Journal Article}, Author = {Jin, K. and Sun, Y. and Xie, L. and Batteur, S. and Mao, X. O. and Smelick, C. and Logvinova, A. and Greenberg, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1474-9718}, Journal = {Aging Cell}, Keywords = {Hippocampus/cytology/drug effects/*metabolism;Animals;Dentate Gyrus/cytology/drug effects/metabolism;Aging;Comparative Study;Epidermal Growth Factor/*pharmacology;*Aging;Heparin/metabolism;Hippocampus;Male;Fibroblast Growth Factor 2;Cerebral Ventricles;Heparin;Mice, Inbred Strains;Research Support, U.S. Gov't, P.H.S.;Neurons;Cerebral Ventricles/cytology/drug effects/*metabolism;Dentate Gyrus;Support, U.S. Gov't, P.H.S.;04 Adult neurogenesis factors;Mice;Neurons/*drug effects/metabolism;Epidermal Growth Factor;Fibroblast Growth Factor 2/*pharmacology;C pdf}, Medline = {22764190}, Month = {6}, Nlm_Id = {101130839}, Number = {3}, Organization = {Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.}, Pages = {175-83}, Pubmed = {12882410}, Title = {Neurogenesis and aging: FGF-2 and HB-EGF restore neurogenesis in hippocampus and subventricular zone of aged mice}, Uuid = {3EF67BBC-8E5F-41FE-AA19-D45DD6F0F468}, Volume = {2}, Year = {2003}, url = {papers/Jin_AgingCell2003.pdf}} @article{Jin:2003a, Abstract = {Bone marrow cells (BMC) can be induced to express neuronal phenotypic features in vitro, but the extent to which they can transdifferentiate to mature, functional neurons is uncertain. We examined the effects of different growth factors and combinations thereof on the expression of neuronal marker proteins in cultures of BMC enriched in marrow stromal cells. Patterns of neuronal marker expression varied depending on the growth factor or factors to which BMC cultures were exposed. Cultures treated for up to 5 weeks with epidermal growth factor, fibroblast growth factor-2, retinoic acid, and nerve growth factor displayed neuron-like cellular processes and expressed neuronal markers, including the neuronal nuclear antigen NeuN, microtubule-associated protein 2, tau, synaptophysin, alpha(1A) and alpha(1B) calcium channel subunits, NR2A glutamate receptor subunits, and gamma-aminobutyric acid. However, the intracellular distribution of these markers was distinct from their usual distribution in mature neurons. We conclude that a variety of growth factors can drive BMC toward a neuronal phenotype or phenotypes, but that morphological neuronal features and the ectopic expression of neuronal proteins and neurotransmitters may not equate with the ability to execute normal neuronal functions.}, Author = {Jin, Kunlin and Mao, Xiao Ou and Batteur, Sophie and Sun, Yunjuan and Greenberg, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cell Differentiation;Animals;Cells, Cultured;Nerve Growth Factors;08 Aberrant cell cycle;Fibroblast Growth Factor 2;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;Neurons;Neuroglia;Epidermal Growth Factor;Mice;Cell Division;Immunohistochemistry;Biological Markers;Tretinoin;Growth Substances}, Medline = {22999018}, Month = {11}, Nlm_Id = {0370712}, Number = {1}, Organization = {Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.}, Pages = {78-89}, Pii = {S001448860300133X}, Pubmed = {14637082}, Title = {Induction of neuronal markers in bone marrow cells: differential effects of growth factors and patterns of intracellular expression}, Uuid = {65047487-57D3-4BCD-B055-A00CEDF47E06}, Volume = {184}, Year = {2003}, url = {papers/Jin_ExpNeurol2003a.pdf}} @article{Jin:2003b, Author = {Jin, Kunlin and Greenberg, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Stromal Cells;Cell Differentiation;Adipose Tissue;Research Support, Non-U.S. Gov't;Bone Marrow Cells;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;Growth Substances;Culture Media;comment;Animals;Cells, Cultured;Humans;Neurons;Mice}, Medline = {22916126}, Month = {10}, Nlm_Id = {0370712}, Number = {2}, Organization = {Buck Institute for Age Research, 8001 Redwood Boulevard, Novato, CA 94945, USA.}, Pages = {255-7}, Pii = {S0014488603002206}, Pubmed = {14552865}, Title = {Tales of transdifferentiation}, Uuid = {04FE95CB-E28E-4F91-BFDB-77285DA34ABD}, Volume = {183}, Year = {2003}, url = {papers/Jin_ExpNeurol2003.pdf}} @article{Jin:2002, Abstract = {Heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is found in cerebral neurons, and its expression is increased after hypoxic or ischemic injury, which also stimulates neurogenesis. To investigate the possible role of HB-EGF in hypoxic-ischemic induction of neurogenesis, we measured its expression, effects, and target receptors in embryonic murine cerebral cortical cultures and in adult rat brain. Hypoxia increased HB-EGF expression by approximately 50\%in cortical cultures, where expression was associated with mature and immature neurons. HB-EGF (5-100 ng/ml) stimulated by approximately 80\%the incorporation of bromodeoxyuridine (BrdU) into cultured cells that expressed the HB-EGF receptors epidermal growth factor receptor (EGFR)/avian erythroblastic leukemia viral oncogene homolog 1 (ErbB1) and N-arginine dibasic convertase (NRDc). Intracerebroventricular administration of HB-EGF in adult rats increased BrdU labeling in the subventricular zone and in the subgranular zone of dentate gyrus, where EGFR/ErbB1 and NRDc were also expressed and where ischemia-induced neurogenesis is observed. We conclude that HB-EGF stimulates neurogenesis in proliferative zones of the adult brain that are also affected in ischemia and that it does so by interacting with EGFR/ErbB1 and possibly NRDc. Therefore, HB-EGF may help to trigger proliferation of neuronal precursors in brain after hypoxic or ischemic injury. 1529-2401 Journal Article}, Author = {Jin, K. and Mao, X. O. and Sun, Y. and Xie, L. and Jin, L. and Nishi, E. and Klagsbrun, M. and Greenberg, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Survival;Animals;Cell Survival/drug effects;Epidermal Growth Factor/*biosynthesis/*pharmacology;Cells, Cultured;Rats;Receptors, Growth Factor;Cerebral Cortex/cytology/*growth &development/metabolism;Cell Hypoxia;Receptors, Growth Factor/analysis;Rats, Sprague-Dawley;Neurons/drug effects/*metabolism;Stem Cells/drug effects/metabolism;C abstr;Male;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neurons;Epidermal Growth Factor;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Stem Cells;Cell Division/drug effects}, Medline = {22092348}, Month = {7}, Nlm_Id = {8102140}, Number = {13}, Organization = {Buck Institute for Age Research, Novato, California 94945, USA.}, Pages = {5365-73}, Pii = {22/13/5365}, Pubmed = {12097488}, Title = {Heparin-binding epidermal growth factor-like growth factor: hypoxia-inducible expression in vitro and stimulation of neurogenesis in vitro and in vivo}, Uuid = {88CAC002-4411-4BBC-B6AE-A4BDACAB79DA}, Volume = {22}, Year = {2002}, url = {papers/Jin_JNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/20026486}} @article{Jin:2006a, Abstract = {Formation of new recurrent excitatory circuits after brain injuries has been hypothesized as a major factor contributing to epileptogenesis. Increases in total axonal length and the density of synaptic boutons are present in layer V pyramidal neurons of chronic partial isolations of rat neocortex, a model of posttraumatic epileptogenesis. To explore the functional consequences of these changes, we used laser-scanning photostimulation combined with whole-cell patch-clamp recording from neurons in layer V of somatosensory cortex to map changes in excitatory synaptic connectivity after injury. Coronal slices were submerged in artificial CSF (23 degrees C) containing 100 microM caged glutamate, APV (2-amino-5-phosphonovaleric acid), and high divalent cation concentration to block polysynaptic responses. Focal uncaging of glutamate, accomplished by switching a pulsed UV laser to give a 200-400 micros light stimulus, evoked single- or multiple-component composite EPSCs. In neurons of the partially isolated cortex, there were significant increases in the fraction of uncaging sites from which EPSCs could be evoked ("hot spots") and a decrease in the mean amplitude of individual elements in the composite EPSC. When plotted along the cortical depth, the changes in EPSCs took place mainly between 150 and 200 microm above and below the somata, suggesting a specific enhancement of recurrent excitatory connectivity among layer V pyramidal neurons of the undercut neocortex. These changes may shift the balance within cortical circuits toward increased synaptic excitation and contribute to epileptogenesis.}, Author = {Jin, Xiaoming and Prince, David A. and Huguenard, John R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8102140}, Number = {18}, Organization = {Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.}, Pages = {4891-900}, Pii = {26/18/4891}, Pubmed = {16672663}, Title = {Enhanced excitatory synaptic connectivity in layer v pyramidal neurons of chronically injured epileptogenic neocortex in rats}, Uuid = {E20A8A15-9A07-46AE-9E34-53FA7AB55AE9}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4361-05.2006}} @article{Jin:2000, Abstract = {A major obstacle to stem-cell gene therapy rests in the inability to deliver a gene into a therapeutically relevant fraction of stem cells. One way to circumvent this obstacle is to use selection. Vectors containing two linked genes serve as the basis for selection, with one gene encoding a selectable product and the other, a therapeutic protein. Applying selection in vivo has the potential to bring a minor population of genetically corrected cells into the therapeutic range. But strategies for achieving in vivo selection have traditionally relied on genes that confer resistance to cytotoxic drugs and are encumbered by toxicity. Here we describe a new system for in vivo selection that uses a 'cell-growth switch', allowing a minor population of genetically corrected cells into the therapeutic range. But strategies for achieving in vivo selection have traditionally relied on genes that confer resistance to cytotoxic drugs and are encumbered by toxicity. Here we describe a new system for in vivo selection that uses a 'cell-growth switch', allowing a minor population of genetically modified cells to be inducibly amplified, thereby averting the risks associated with cytotoxic drugs. This system provides a general platform for conditionally expanding genetically modified cell populations in vivo, and may have widespread applications in gene and cell therapy.}, Author = {Jin, L. and Zeng, H. and Chien, S. and Otto, K. G. and Richard, R. E. and Emery, D. W. and Blau, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Protein Structure, Tertiary;Genetic Vectors;Green Fluorescent Proteins;Erythrocytes;Luminescent Proteins;Gene Therapy;Animals;Cell Separation;Flow Cytometry;Dimerization;Research Support, U.S. Gov't, P.H.S.;Transgenes;Kinetics;Phenotype;Proto-Oncogene Proteins;Bone Marrow Transplantation;Receptors, Cytokine;Blotting, Southern;Receptors, Erythropoietin;Granulocytes;11 Glia;Neoplasm Proteins;Blood Platelets;Retroviridae;Time Factors;Dose-Response Relationship, Drug;Recombinant Fusion Proteins;Mice;Research Support, Non-U.S. Gov't;Cell Culture Techniques;Oncogene Proteins}, Medline = {20428183}, Month = {9}, Nlm_Id = {9216904}, Number = {1}, Organization = {Division of Hematology, Department of Medicine, University of Washington, Seattle, Washington, USA.}, Pages = {64-6}, Pubmed = {10973250}, Title = {In vivo selection using a cell-growth switch}, Uuid = {8339F942-B570-480C-8409-16F13336F199}, Volume = {26}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/79194}} @article{Jin:2001, Abstract = {Because neurogenesis persists in the adult mammalian brain and can be regulated by physiological and pathological events, we investigated its possible involvement in the brain's response to focal cerebral ischemia. Ischemia was induced by occlusion of the middle cerebral artery in the rat for 90 min, and proliferating cells were labeled with 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdUrd) over 2-day periods before sacrificing animals 1, 2 or 3 weeks after ischemia. Ischemia increased the incorporation of BrdUrd into cells in two neuroproliferative regions-the subgranular zone of the dentate gyrus and the rostral subventricular zone. Both effects were bilateral, but that in the subgranular zone was more prominent on the ischemic side. Cells labeled with BrdUrd coexpressed the immature neuronal markers doublecortin and proliferating cell nuclear antigen but did not express the more mature cell markers NeuN and Hu, suggesting that they were nascent neurons. These results support a role for ischemia-induced neurogenesis in what may be adaptive processes that contribute to recovery after stroke. 0027-8424 Journal Article}, Author = {Jin, K. and Minami, M. and Lan, J. Q. and Mao, X. O. and Batteur, S. and Simon, R. P. and Greenberg, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Dentate Gyrus/metabolism/pathology/*physiopathology;Rats, Sprague-Dawley;Proliferating Cell Nuclear Antigen/metabolism;Immunohistochemistry;Rats;Bromodeoxyuridine/metabolism;06 Adult neurogenesis injury induced;Brain Ischemia/metabolism/pathology/*physiopathology;Neuropeptides/metabolism;Support, U.S. Gov't, P.H.S.;D pdf;Animals;Male}, Number = {8}, Organization = {Buck Institute for Age Research, Novato, CA 94945, USA.}, Pages = {4710-5}, Title = {Neurogenesis in dentate subgranular zone and rostral subventricular zone after focal cerebral ischemia in the rat}, Uuid = {6D9248FE-EC81-11DA-8605-000D9346EC2A}, Volume = {98}, Year = {2001}, url = {papers/Jin_ProcNatlAcadSciUSA2001.pdf}} @article{Jin:2004, Abstract = {Neurogenesis, which persists in the adult mammalian brain, may provide a basis for neuronal replacement therapy in neurodegenerative diseases like Alzheimer's disease (AD). Neurogenesis is increased in certain acute neurological disorders, such as ischemia and epilepsy, but the effect of more chronic neurodegenerations is uncertain, and some animal models of AD show impaired neurogenesis. To determine how neurogenesis is affected in the brains of patients with AD, we investigated the expression of immature neuronal marker proteins that signal the birth of new neurons in the hippocampus of AD patients. Compared to controls, Alzheimer's brains showed increased expression of doublecortin, polysialylated nerve cell adhesion molecule, neurogenic differentiation factor and TUC-4. Expression of doublecortin and TUC-4 was associated with neurons in the neuroproliferative (subgranular) zone of the dentate gyrus, the physiological destination of these neurons (granule cell layer), and the CA1 region of Ammon's horn, which is the principal site of hippocampal pathology in AD. These findings suggest that neurogenesis is increased in AD hippocampus, where it may give rise to cells that replace neurons lost in the disease, and that stimulating hippocampal neurogenesis might provide a new treatment strategy.}, Author = {Jin, Kunlin and Peel, Alyson L. and Mao, Xiao Ou and Xie, Lin and Cottrell, Barbara A. and Henshall, David C. and Greenberg, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Human;Nerve Degeneration;Animals;Middle Aged;Female;21 Neurodegenerative;Hippocampus;Male;Neuropeptides;Aged;Support, Non-U.S. Gov't;Case-Control Studies;Alzheimer Disease;Sialic Acids;21 Neurophysiology;Aged, 80 and over;Adult;Neurons;Support, U.S. Gov't, P.H.S.;Neural Cell Adhesion Molecule L1;Immunohistochemistry;Nerve Tissue Proteins;Adolescent}, Month = {1}, Nlm_Id = {7505876}, Number = {1}, Organization = {Buck Institute for Age Research, Novato, CA 94945, USA.}, Pages = {343-7}, Pii = {2634794100}, Pubmed = {14660786}, Title = {Increased hippocampal neurogenesis in Alzheimer's disease}, Uuid = {54B36CC8-A2F6-4D51-BE18-BC66F92F6D1F}, Volume = {101}, Year = {2004}, url = {papers/Jin_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.2634794100}} @article{Jin:2004a, Abstract = {Neurogenesis continues in the adult brain and is increased in certain pathological states. We reported recently that neurogenesis is enhanced in hippocampus of patients with Alzheimer's disease (AD). We now report that the effect of AD on neurogenesis can be reproduced in a transgenic mouse model. PDGF-APP(Sw,Ind) mice, which express the Swedish and Indiana amyloid precursor protein mutations, show increased incorporation of BrdUrd and expression of immature neuronal markers in two neuroproliferative regions: the dentate gyrus and subventricular zone. These changes, consisting of approximately 2-fold increases in the number of BrdUrd-labeled cells, were observed at age 3 months, when neuronal loss and amyloid deposition are not detected. Because enhanced neurogenesis occurs in both AD and an animal model of AD, it seems to be caused by the disease itself and not by confounding clinical factors. As neurogenesis is increased in PDGF-APP(Sw,Ind) mice in the absence of neuronal loss, it must be triggered by more subtle disease manifestations, such as impaired neurotransmission. Enhanced neurogenesis in AD and animal models of AD suggests that neurogenesis may be a compensatory response and that measures to enhance neurogenesis further could have therapeutic potential.}, Author = {Jin, Kunlin and Galvan, Veronica and Xie, Lin and Mao, Xiao Ou and Gorostiza, Olivia F. and Bredesen, Dale E. and Greenberg, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Platelet-Derived Growth Factor;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred C57BL;06 Adult neurogenesis injury induced;Alzheimer Disease;Mice, Transgenic;Amyloid beta-Protein Precursor;Animals;Bromodeoxyuridine;Mice;Neurons}, Month = {9}, Nlm_Id = {7505876}, Number = {36}, Organization = {Buck Institute for Age Research, Novato, CA 94945, USA.}, Pages = {13363-7}, Pii = {0403678101}, Pubmed = {15340159}, Title = {Enhanced neurogenesis in Alzheimer's disease transgenic (PDGF-APPSw,Ind) mice}, Uuid = {E5401220-E44E-4CD8-8DD5-0D7B1236A9EA}, Volume = {101}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0403678101}} @article{Jin:2006, Abstract = {Experimental stroke in rodents stimulates neurogenesis and migration of newborn neurons from their sites of origin into ischemic brain regions. We report that in patients with stroke, cells that express markers associated with newborn neurons are present in the ischemic penumbra surrounding cerebral cortical infarcts, where these cells are preferentially localized in the vicinity of blood vessels. These findings suggest that stroke-induced compensatory neurogenesis may occur in the human brain, where it could contribute to postischemic recovery and represent a target for stroke therapy.}, Author = {Jin, Kunlin and Wang, Xiaomei and Xie, Lin and Mao, Xiao Ou and Zhu, Wei and Wang, Yin and Shen, Jianfeng and Mao, Ying and Banwait, Surita and Greenberg, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cerebrovascular Accident;Brain Ischemia;Cell Differentiation;research support, n.i.h., extramural ;Adult;Aged;Cell Proliferation;Female;Middle Aged;research support, u.s. gov't, non-p.h.s. ;Male;Humans;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {35}, Organization = {*Buck Institute for Age Research, Novato, CA 94945.}, Pages = {13198-202}, Pii = {0603512103}, Pubmed = {16924107}, Title = {Evidence for stroke-induced neurogenesis in the human brain}, Uuid = {A9B027F8-A75F-44E1-BE3E-547680B65107}, Volume = {103}, Year = {2006}, url = {papers/Jin_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0603512103}} @article{Jinno:2007a, Abstract = {Microglia are classically considered to be immune cells in the brain, but have now been proven to be involved in neuronal activity as well. Here we stereologically analyzed the spatial arrangement of microglia in the mouse hippocampus. First, we estimated the numerical densities (NDs) of microglia identified by ionized calcium-binding adaptor molecule 1 (Iba1). Despite that microglia appeared to be evenly distributed throughout the hippocampal area, the NDs demonstrated significant dorsoventral, interregional, and interlaminar differences. Briefly, the NDs in the ventral hippocampus were significantly lower in the CA3 region than in the CA1 region and dentate gyrus, although no interregional differences were detectable in the dorsal hippocampus. Both in the CA1 and CA3 regions, the NDs were significantly higher in the stratum lacunosum-moleculare than in the remaining layers. Next, we investigated the spatial patterns of distribution of Iba1-labeled microglia and S100beta-labeled astrocytes. So far as we examined, the somato-somatic contacts were not seen among microglia or among astrocytes, whereas the close apposition between microglia and astrocytes were occasionally detected. The 3D point process analysis showed that the spatial distribution of microglia was significantly repulsive. Because the statistical territory of single microglia was larger than that estimated from process tracing, they are not likely to touch each other with their processes. Astrocytes were distributed slightly repulsively with overlapping areas. The 3D point process analysis also revealed a significant spatial attraction between microglia and astrocytes. The present findings provide a novel anatomical basis for glial research.}, Author = {Jinno, Shozo and Fleischer, Frank and Eckel, Stefanie and Schmidt, Volker and Kosaka, Toshio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Animals;Astrocytes;Image Processing, Computer-Assisted;comparative study;Imaging, Three-Dimensional;Microglia;Cell Communication;Cell Count;Hippocampus;Staining and Labeling;Mice, Inbred C57BL;research support, non-u.s. gov't;11 Glia;Male;Nerve Growth Factors;Calcium-Binding Proteins;Dentate Gyrus;Poisson Distribution;Mice;24 Pubmed search results 2008;S100 Proteins;Immunologic Techniques}, Month = {10}, Nlm_Id = {8806785}, Number = {13}, Organization = {Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan. sjnno\@med.kyushu-u.ac.jp}, Pages = {1334-47}, Pubmed = {17647290}, Title = {Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes}, Uuid = {F972761F-0BBE-49D2-9521-103AB9AC3B8C}, Volume = {55}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20552}} @article{Jinno:2007, Abstract = {The formation and recall of sensory, motor, and cognitive representations require coordinated fast communication among multiple cortical areas. Interareal projections are mainly mediated by glutamatergic pyramidal cell projections; only few long-range GABAergic connections have been reported. Using in vivo recording and labeling of single cells and retrograde axonal tracing, we demonstrate novel long-range GABAergic projection neurons in the rat hippocampus: (1) somatostatin- and predominantly mGluR1alpha-positive neurons in stratum oriens project to the subiculum, other cortical areas, and the medial septum; (2) neurons in stratum oriens, including somatostatin-negative ones; and (3) trilaminar cells project to the subiculum and/or other cortical areas but not the septum. These three populations strongly increase their firing during sharp wave-associated ripple oscillations, communicating this network state to the septotemporal system. Finally, a large population of somatostatin-negative GABAergic cells in stratum radiatum project to the molecular layers of the subiculum, presubiculum, retrosplenial cortex, and indusium griseum and fire rhythmically at high rates during theta oscillations but do not increase their firing during ripples. The GABAergic projection axons have a larger diameter and thicker myelin sheet than those of CA1 pyramidal cells. Therefore, rhythmic IPSCs are likely to precede the arrival of excitation in cortical areas (e.g., subiculum) that receive both glutamatergic and GABAergic projections from the CA1 area. Other areas, including the retrosplenial cortex, receive only rhythmic GABAergic CA1 input. We conclude that direct GABAergic projections from the hippocampus to other cortical areas and the septum contribute to coordinating oscillatory timing across structures.}, Author = {Jinno, Shozo and Klausberger, Thomas and Marton, Laszlo F. and Dalezios, Yannis and Roberts, J. David B. and Fuentealba, Pablo and Bushong, Eric A. and Henze, Darrell and Buzs{\'a}ki, Gy{\"o}rgy and Somogyi, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Brain Mapping;gamma-Aminobutyric Acid;Animals;Rats;Dextrans;Neural Pathways;Rats, Sprague-Dawley;Hippocampus;research support, non-u.s. gov't;Male;Stilbamidines;Action Potentials;Somatostatin;Inhibitory Postsynaptic Potentials;21 Neurophysiology;21 Circuit structure-function;Neurons;research support, n.i.h., extramural;Microscopy, Electron, Transmission;24 Pubmed search results 2008;Receptors, Metabotropic Glutamate;Biotin;Models, Neurological;Nerve Tissue Proteins;Phytohemagglutinins}, Month = {8}, Nlm_Id = {8102140}, Number = {33}, Organization = {Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, Oxford University, Oxford, United Kingdom. sjnno\@med.kyushu-u.ac.jp}, Pages = {8790-804}, Pii = {27/33/8790}, Pubmed = {17699661}, Title = {Neuronal diversity in GABAergic long-range projections from the hippocampus}, Uuid = {C034F2E8-B3A4-4EE5-B8F1-FDDD77FECB5C}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1847-07.2007}} @article{Joannides:2004, Abstract = {Background Neural stem cells are a potential source of cells for drug screening or cell-based treatments for neurodegenerative diseases. However, ethical and practical considerations limit the availability of neural stem cells derived from human embryonic tissue. An alternative source of human neural stem cells is needed; a source that is readily accessible, easily expanded, and reliably induced to a neural fate. Methods Dermis isolated from biopsy samples of adult human skin was cultured and expanded in the presence of the mitogens epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF 2), and then by serum. We used immunocytochemical techniques, clonal analysis, and physiological characterisation to assess neural differentiation after the treatment of expanded cells with novel induction media. Findings Initial characterisation of skin samples confirmed the absence of nestin, a neural precursor marker. Sequential culture in EGF and FGF 2 followed by adherent expansion in serum, and re-exposure to mitogens in substrate-free conditions resulted in large numbers of nestin-positive/musashi-positive neural precursors. Subsequent exposure of these precursors to hippocampal-astrocyte-derived signals resulted in cells of neuronal morphology that had stable expression of markers of neuronal differentiation (neurofilament, beta tubulin). We also show the presence of voltage-dependent calcium transients, and demonstrate monoclonal neural potential. Interpretation We describe the isolation and characterisation of cells derived from adult human dermis that can be expanded for extended periods of time in vitro, while retaining inducible neural potential. The generation of almost limitless numbers of neural precursors from a readily accessible autologous adult human source provides a platform for further experimental studies and has potential therapeutic implications. 1474-547x Journal Article}, Author = {Joannides, A. and Gaughwin, P. and Schwiening, C. and Majed, H. and Sterling, J. and Compston, P. A. and Chandran, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Lancet}, Keywords = {S abstr;22 Stem cells}, Number = {9429}, Organization = {Department of Clinical Neurosciences, University of Cambridge and Addenbrooke's Hospital, Cambridge, UK.}, Pages = {172-8}, Pubmed = {15246730}, Title = {Efficient generation of neural precursors from adult human skin: astrocytes promote neurogenesis from skin-derived stem cells}, Uuid = {B400C25C-2D47-4C10-9082-55904A06C0E9}, Volume = {364}, Year = {2004}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15246730}} @article{Jockusch:2003, Abstract = {We studied the migratory behaviour of adult muscle precursor cells in the mouse into and from skeletal muscle grafts using green fluorescent protein (GFP) and nuclear LacZ transgenes as complementary and double markers of the cell's origin. Owing to the small molecular mass and extreme solubility of GFP, this label provided a drastically increased sensitivity for detection compared with the markers that had been used previously. During the first six weeks after the operation, the graft/host border was well defined, with only occasional local intermingling and co-fusion of host and donor myogenic cells. Seven to eleven weeks after the operation we found that the host myogenic cells had migrated into the graft, and graft myogenic cells had migrated into the adjacent host muscle, with integration of donor nuclei into pre-existing myotubes or muscle fibres. There was no indication of an origin of, or target for, these myogenic cells besides neighbouring muscles. Our observations indicate migration of these cells through solid muscle tissue, over a distance of several millimetres. The migratory activity of adult myogenic precursor cells can be stimulated by traumatic events in either the target muscle or the muscle of origin.}, Author = {Jockusch, Harald and Voigt, Sylvana}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0021-9533}, Journal = {J Cell Sci}, Keywords = {Animals;Female;Myoblasts;Cell Movement;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Time Factors;Mice, Nude;Male;Transplantation Chimera;Mice, Inbred Strains;Lac Operon;Mice;Muscle, Smooth, Vascular;Luminescent Proteins;Nuclear Proteins;Research Support, Non-U.S. Gov't}, Medline = {22526791}, Month = {4}, Nlm_Id = {0052457}, Number = {Pt 8}, Organization = {Developmental Biology and Molecular Pathology, W7, University of Bielefeld, D-33501 Bielefeld, Germany. h.jockusch\@uni-bielfeld.de}, Pages = {1611-6}, Pubmed = {12640044}, Title = {Migration of adult myogenic precursor cells as revealed by GFP/nLacZ labelling of mouse transplantation chimeras}, Uuid = {7ECC4343-24D5-464D-ADC1-0D67561C6026}, Volume = {116}, Year = {2003}} @article{Joels:2004, Abstract = {It has become increasingly clear that the increase in corticosteroid levels, e.g. after a brief stressor induce molecular and cellular changes in brain, including the hippocampal formation. These effects eventually result in behavioral adaptation. Prolonged exposure to stress, though, may lead to mal-adaptation and even be a risk factor for diseases like major depression in genetically predisposed individuals. We conducted a series of experiments where changes in brain function were examined after 3 weeks of unpredictable stress. After unpredictable stress, inhibitory input to neurons involved in the hypothalamus-pituitary-adrenal (HPA) axis regulation was suppressed, which may dysregulate the axis and lead to overexposure of the brain to glucocorticoids. Furthermore, glutamate transmission in the dentate gyrus (DG) was enhanced, possibly through transcriptional regulation of receptor subunits. Combined with enhanced calcium channel expression this could increase vulnerability to cell death. Neurogenesis and apoptosis in the dentate were diminished. Synaptic plasticity was suppressed both in the dentate and CA1 area. Collectively, these effects may give rise to deficits in memory formation. Finally, we observed reduced responses to serotonin in the CA1 area, which could contribute to the onset of symptoms of depression in predisposed individuals. All of these endpoints provide potential targets for novel treatment strategies of stress-related brain disorders.}, Author = {Jo{\"e}ls, Marian and Karst, Henk and Alfarez, Deborah and Heine, Vivi M. and Qin, Yongjun and van Riel, Els and Verkuyl, Martin and Lucassen, Paul J. and Krugers, Harm J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1025-3890}, Journal = {Stress}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9617529}, Number = {4}, Organization = {SILS-CNS, University of Amsterdam, The Netherlands. joels\@science.uva.nl}, Pages = {221-31}, Pii = {H7L632V754R125V0}, Pubmed = {16019587}, Title = {Effects of chronic stress on structure and cell function in rat hippocampus and hypothalamus}, Uuid = {F42CD4B1-1DE9-49FA-A80C-B2F5792ECCA5}, Volume = {7}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/10253890500070005}} @article{Johansson:1999, Abstract = {New neurons are continuously added in specific regions of the adult mammalian central nervous system. These neurons are derived from multipotent stem cells whose identity has been enigmatic. In this work, we present evidence that ependymal cells are neural stem cells. Ependymal cells give rise to a rapidly proliferating cell type that generates neurons that migrate to the olfactory bulb. In response to spinal cord injury, ependymal cell proliferation increases dramatically to generate migratory cells that differentiate to astrocytes and participate in scar formation. These data demonstrate that ependymal cells are neural stem cells and identify a novel process in the response to central nervous system injury.}, Author = {Johansson, C. B. and Momma, S. and Clarke, D. L. and Risling, M. and Lendahl, U. and Frisen, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Cell}, Keywords = {Stem Cells/cytology/*physiology;Astrocytes/cytology/physiology;Rats;Spinal Cord Injuries/physiopathology;Neurons/cytology/*physiology;Animal;Central Nervous System/*cytology;02 Adult neurogenesis migration;Mammals;Membrane Proteins/analysis;Heart Ventricle/cytology;Support, Non-U.S. Gov't;Spinal Cord/cytology;Olfactory Bulb/cytology;Mice;Cell Division;B-15;Biological Markers}, Number = {1}, Organization = {Department of Cell and Molecular Biology, Karolinska Institute, Stockholm, Sweden.}, Pages = {25-34.}, Title = {Identification of a neural stem cell in the adult mammalian central nervous system}, Uuid = {7D641BB2-71AE-4780-B5FE-EBC6DB7F0AF8}, Volume = {96}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9989494}} @article{John:2003, Abstract = {It is now clear that cytokines function as powerful regulators of glial cell function in the central nervous system (CNS), either inhibiting or promoting their contribution to CNS pathology. Although these interactions are complex, the availability of animals with targeted deletions of these genes and/or their receptors, as well as transgenic mice in which cytokine expression has been targeted to specific cell types, and the availability of purified populations of glia that can be studied in vitro, has provided a wealth of interesting and frequently surprising data relevant to this activity. A particular feature of many of these studies is that it is the nature of the receptor that is expressed, rather than the cytokine itself, that regulates the functional properties of these cytokines. Because cytokine receptors are themselves modulated by cytokines, it becomes evident that the effects of these cytokines may change dramatically depending upon the cytokine milieu present in the immediate environment. An additional exciting aspect of these studies is the previously underappreciated role of these factors in repair to the CNS. In this review, we focus on current information that has helped to define the role of cytokines in regulating glial cell function as it relates to the properties of microglia and astrocytes.}, Author = {John, Gareth R. and Lee, Sunhee C. and Brosnan, Celia F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1073-8584}, Journal = {Neuroscientist}, Keywords = {Human;Tumor Necrosis Factor;Animals;Astrocytes;Transforming Growth Factor beta;review, tutorial;review;Interferon Type II;Microglia;11 Glia;Nerve Growth Factors;Support, Non-U.S. Gov't;Neuroglia;Interleukin-1;Support, U.S. Gov't, P.H.S.;Interleukin-6;Central Nervous System;Cell Death;Cytokines}, Medline = {22467748}, Month = {2}, Nlm_Id = {9504819}, Number = {1}, Organization = {Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.}, Pages = {10-22}, Pubmed = {12580336}, Title = {Cytokines: powerful regulators of glial cell activation}, Uuid = {7CBEC163-6F9A-4AFB-A4C5-C71C525F41C2}, Volume = {9}, Year = {2003}, url = {papers/John_Neuroscientist2003.pdf}} @article{Johnson:2005, Abstract = {It has been suggested that germline stem cells maintain oogenesis in postnatal mouse ovaries. Here we show that adult mouse ovaries rapidly generate hundreds of oocytes, despite a small premeiotic germ cell pool. In considering the possibility of an extragonadal source of germ cells, we show expression of germline markers in bone marrow (BM). Further, BM transplantation restores oocyte production in wild-type mice sterilized by chemotherapy, as well as in ataxia telangiectasia-mutated gene-deficient mice, which are otherwise incapable of making oocytes. Donor-derived oocytes are also observed in female mice following peripheral blood transplantation. Although the fertilizability and developmental competency of the BM and peripheral blood-derived oocytes remain to be established, their morphology, enclosure within follicles, and expression of germ-cell- and oocyte-specific markers collectively support that these cells are bona fide oocytes. These results identify BM as a potential source of germ cells that could sustain oocyte production in adulthood.}, Author = {Johnson, Joshua and Bagley, Jessamyn and Skaznik-Wikiel, Malgorzata and Lee, Ho-Joon J. and Adams, Gregor B. and Niikura, Yuichi and Tschudy, Katherine S. and Tilly, Jacqueline Canning and Cortes, Maria L. and Forkert, Randolf and Spitzer, Thomas and Iacomini, John and Scadden, David T. and Tilly, Jonathan L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Cell Cycle Proteins;Oogenesis;DNA-Binding Proteins;Animals;Mice, Mutant Strains;Bone Marrow Transplantation;Humans;Female;Oocytes;Ovary;Mice, Transgenic;Protein-Serine-Threonine Kinases;Bone Marrow;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Adult;Peripheral Blood Stem Cell Transplantation;Mice;Tumor Suppressor Proteins;22 Stem cells;Sterilization, Reproductive;Biological Markers;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {0413066}, Number = {2}, Organization = {Vincent Center for Reproductive Biology, Vincent Obstetrics and Gynecology Service, Harvard Medical School, Boston, Massachusetts 02114, USA.}, Pages = {303-15}, Pii = {S0092-8674(05)00650-1}, Pubmed = {16051153}, Title = {Oocyte generation in adult mammalian ovaries by putative germ cells in bone marrow and peripheral blood}, Uuid = {78DE01CF-7CDB-4F6A-A339-51B21FC6F9CD}, Volume = {122}, Year = {2005}, url = {papers/Johnson_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.06.031}} @article{Johnston:2001, Abstract = {Human endogenous retroviruses (HERVs) have been implicated as causative agents in diseases characterized by inflammation and macrophage activation, such as multiple sclerosis. Because monocyte activation and differentiation influence retroviral transcription and replication, we investigated the contribution of these processes to the expression of four HERV families (HERV-W, HERV-K, HERV-E, and HERV-H) in human monocytes, and autopsied brain tissue from patients with brain diseases associated with increased macrophage activity. Reverse transcriptase-polymerase chain reaction analysis of primary macrophages and U937 monocytoid cells stimulated with phorbol-12-myristate-13-acetate or lipopolysaccharide revealed three- to ninefold increases in HERV-W, HERV-K, and HERV-H RNA levels. In addition, elevated reverse transcriptase activity and HERV RNA were detectable in supernatants from PMA-stimulated U937 cultures, properties that could be attenuated with the inhibitor of monocyte differentiation threonine-lysine-proline. In contrast, stimulation of monocytes decreased or had no effect on HERV-E expression. Compared with controls, HERV-W and HERV-K expression was increased in brain tissue from patients with multiple sclerosis or human immunodeficiency virus infection or AIDS, with concomitant elevated tumor necrosis factor-alpha levels. Similarly, elevated HERV-W levels were detected in patients with Alzheimer's dementia only when tumor necrosis factor-alpha expression was also evident (2 of 6 cases). The detection of several HERVs in inflammatory brain diseases and the capacity to augment HERV expression in monocytes with compounds that influence cellular activity suggest that increased expression of these viruses is a consequence of increased immune activity rather than causative of distinct diseases.}, Author = {Johnston, J. B. and Silva, C. and Holden, J. and Warren, K. G. and Clark, A. W. and Power, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {RNA, Viral;Cell Differentiation;Monocytes;Encephalitis;U937 Cells;Middle Aged;Tumor Necrosis Factor-alpha;Phenotype;Humans;Brain;Female;15 Retrovirus mechanism;Lipopolysaccharides;Endogenous Retroviruses;Male;Reverse Transcriptase Polymerase Chain Reaction;Aged;Carcinogens;Tetradecanoylphorbol Acetate;Adult;24 Pubmed search results 2008;Gene Expression;15 ERVs retroelements;Research Support, Non-U.S. Gov't}, Medline = {21487102}, Month = {10}, Nlm_Id = {7707449}, Number = {4}, Organization = {Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.}, Pages = {434-42}, Pubmed = {11601494}, Title = {Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases}, Uuid = {833A2DFF-4326-11DB-A5D2-000D9346EC2A}, Volume = {50}, Year = {2001}} @article{Johnston:2003, Abstract = {How left/right functional asymmetry is layered on top of an anatomically symmetrical nervous system is poorly understood. In the nematode Caenorhabditis elegans, two morphologically bilateral taste receptor neurons, ASE left (ASEL) and ASE right (ASER), display a left/right asymmetrical expression pattern of putative chemoreceptor genes that correlates with a diversification of chemosensory specificities. Here we show that a previously undefined microRNA termed lsy-6 controls this neuronal left/right asymmetry of chemosensory receptor expression. lsy-6 mutants that we retrieved from a genetic screen for defects in neuronal left/right asymmetry display a loss of the ASEL-specific chemoreceptor expression profile with a concomitant gain of the ASER-specific profile. A lsy-6 reporter gene construct is expressed in less than ten neurons including ASEL, but not ASER. lsy-6 exerts its effects on ASEL through repression of cog-1, an Nkx-type homeobox gene, which contains a lsy-6 complementary site in its 3'untranslated region and that has been shown to control ASE-specific chemoreceptor expression profiles. lsy-6 is the first microRNA to our knowledge with a role in neuronal patterning, providing new insights into left/right axis formation. 1476-4687 Journal Article}, Author = {Johnston, R. J. and Hobert, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-13 09:45:17 -0400}, Journal = {Nature}, Keywords = {Genes, Helminth/*genetics;Base Sequence;10 Development;Cell Differentiation;3'Untranslated Regions/genetics;MicroRNAs/genetics/*metabolism;Nervous System/cytology/*embryology/*metabolism;Gene Expression Regulation;Support, U.S. Gov't, Non-P.H.S.;Caenorhabditis elegans/anatomy &histology/cytology/*embryology/*genetics;Support, U.S. Gov't, P.H.S.;Animals;F pdf;Cell Lineage;*Body Patterning; microRNAs; development}, Number = {6968}, Organization = {Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, College of Physicians and Surgeons, 701 W.168th Street, New York, New York 10032, USA.}, Pages = {845-9}, Pubmed = {14685240}, Title = {A microRNA controlling left/right neuronal asymmetry in Caenorhabditis elegans}, Uuid = {F8932CB7-EC7B-4E6E-9EB1-8C2BD64DE8B0}, Volume = {426}, Year = {2003}, url = {papers/Johnston_Nature2003.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14685240}} @article{Jolicoeur:2003, Abstract = {Some murine leukemia viruses (MuLVs), among them Cas-Br-E and ts-1 MuLVs, are neurovirulent, inducing spongiform myeloencephalopathy and hind limb paralysis in susceptible mice. It has been shown that the env gene of these viruses harbors the determinant of neurovirulence. It appears that neuronal loss occurs by an indirect mechanism, since the target motor neurons have not been found to be infected. However, the pathogenesis of the disease remains unclear. Several lymphokines, cytokines, and other cellular effectors have been found to be aberrantly expressed in the brains of infected mice, but whether these are required for the development of the neurodegenerative lesions is not known. In an effort to identify the specific effectors which are indeed required for the initiation and/or development of spongiform myeloencephalopathy, we inoculated gene-deficient (knockout [KO]) mice with ts-1 MuLV. We show here that interleukin-6 (IL-6), inducible nitric oxide synthetase (iNOS), ICE, Fas, Fas ligand (FasL), and TNF-R1 KO mice still develop signs of disease. However, transgenic mice overexpressing Bcl-2 in neurons (NSE/Bcl-2) were largely protected from hind limb paralysis and had less-severe spongiform lesions. These results indicate that motor neuron death occurs in this disease at least in part by a Bcl-2-inhibitable pathway not requiring the ICE, iNOS, Fas/FasL, TNF-R1, and IL-6 gene products.}, Author = {Jolicoeur, Paul and Hu, Chunyan and Mak, Tak W. and Martinou, Jean-Claude C. and Kay, Denis G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Caspase 1;Nerve Degeneration;Animals;Central Nervous System Viral Diseases;Mice, Inbred C3H;Antigens, CD;Mice, Transgenic;Nitric-Oxide Synthase;Not relevant;11 Glia;Receptors, Tumor Necrosis Factor;Leukemia Virus, Murine;Proto-Oncogene Proteins c-bcl-2;Retroviridae Infections;Support, Non-U.S. Gov't;Membrane Glycoproteins;Mice, Knockout;Neurons;Mice;Interleukin-6;Antigens, CD95}, Month = {12}, Nlm_Id = {0113724}, Number = {24}, Organization = {Laboratory of Molecular Biology, Clinical Research Institute of Montreal, Montreal, Quebec H2W 1R7, Canada. jolicop\@ircm.qc.ca}, Pages = {13161-70}, Pubmed = {14645573}, Title = {Protection against murine leukemia virus-induced spongiform myeloencephalopathy in mice overexpressing Bcl-2 but not in mice deficient for interleukin-6, inducible nitric oxide synthetase, ICE, Fas, Fas ligand, or TNF-R1 genes}, Uuid = {16309A3E-ACCF-4545-A5BF-BFBEA465FA7A}, Volume = {77}, Year = {2003}, url = {papers/Jolicoeur_JVirol2003.pdf}} @article{Jones:2005, Abstract = {Theta phase-locking and phase precession are two related phenomena reflecting coordination of hippocampal place cell firing with the local, ongoing theta rhythm. The mechanisms and functions of both the phenomena remain unclear, though the robust correlation between firing phase and location of the animal has lead to the suggestion that this phase relationship constitutes a temporal code for spatial information. Recent work has described theta phase-locking in the rat medial prefrontal cortex (mPFC), a structure with direct anatomical and functional links to the hippocampus. Here, we describe an initial characterization of phase precession in the mPFC relative to the CA1 theta rhythm. mPFC phase precession was most robust during behavioral epochs known to be associated with enhanced theta-frequency coordination of CA1 and mPFC activities. Precession was coherent across the mPFC population, with multiple neurons precessing in parallel as a function of location of the animal. The existence of phase precession beyond the hippocampus implies a more global role for this phenomenon during theta rhythm-mediated coordination of neural activity.}, Author = {Jones, Matthew W. and Wilson, Matthew A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {1050-9631}, Journal = {Hippocampus}, Keywords = {research support, u.s. gov't, p.h.s. ;Theta Rhythm;research support, n.i.h., extramural ;21 Neurophysiology;Orientation;Rats;Rats, Long-Evans;Space Perception;research support, non-u.s. gov't ;Action Potentials;Prefrontal Cortex;Hippocampus;Synaptic Transmission;Animals;Male;24 Pubmed search results 2008;Neurons}, Nlm_Id = {9108167}, Number = {7}, Organization = {Department of Brain and Cognitive Sciences, The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Massachusetts Institute of Technology, Cambridge, 02139, USA.}, Pages = {867-73}, Pubmed = {16149084}, Title = {Phase precession of medial prefrontal cortical activity relative to the hippocampal theta rhythm}, Uuid = {3371E999-2147-48D3-8B47-983DB5F58297}, Volume = {15}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/hipo.20119}} @article{Jones:1997, Abstract = {Brain lesions, even of the most subtle type, are accompanied by the activation of microglia, the main immune cells of the brain. Microglial cells dramatically increase in number through proliferation and adhere to the injured neurons, where they displace the synaptic input. After proliferation, microglia gradually migrate into the nearby parenchyma and appear to decrease in number. Here we examined the possible involvement of apoptosis in the regulation of the microglial cell number using Terminal transferase mediated d-UTP Nick End-Labelling (TUNEL). In vitro, cell death is a common phenomenon in microglial cell cultures, and is enhanced by the withdrawal of the mitogen, granulocyte-macrophage colony stimulating factor. In vivo, application of the TUNEL-reaction revealed TUNEL-positive microglia beginning at day 4, with a peak 7 days after transection of the facial nerve. Surprisingly, TUNEL-labelling in vivo was localized on the outer side of the nuclear membrane and in the microglial cytoplasm, with very little staining within the nucleus itself. These TUNEL-labelled cells also lacked other classic morphological signs of apoptosis, like membrane blebbing, chromatin condensation and apoptotic bodies. These data suggest that the regulation of post-mitotic microglia is not mediated by the classic pathway of apoptosis.}, Author = {Jones, L. L. and Banati, R. B. and Graeber, M. B. and Bonfanti, L. and Raivich, G. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Facial Nerve;Homeostasis;Rats;Microscopy, Electron;Apoptosis;Immunohistochemistry;Rats, Wistar;DNA Nucleotidylexotransferase;11 Glia;Microglia;Animals, Newborn;Male;Brain;Axotomy;Cells, Cultured;Animals}, Medline = {98086141}, Month = {11}, Nlm_Id = {0364620}, Number = {11}, Organization = {Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, Germany.}, Pages = {755-70}, Pubmed = {9426172}, Title = {Population control of microglia: does apoptosis play a role?}, Uuid = {99AFF81C-CE04-447A-9AB7-33387F3B1BCE}, Volume = {26}, Year = {1997}} @article{Jones:2007, Abstract = {Periodic bursts of activity in the disinhibited in vitro hippocampal CA3 network spread through the neural population by the glutamatergic recurrent collateral axons that link CA3 pyramidal cells. It was previously proposed that these bursts of activity are terminated by exhaustion of releasable glutamate at the recurrent collateral synapses so that the next periodic burst of network activity cannot occur until the supply of glutamate has been replenished. As a test of this hypothesis, the rate of glutamate release at CA3 axon terminals was reduced by substitution of extracellular Ca(2+) with Sr(2+). Reduction of the rate of glutamate release reduces the rate of depletion and should thereby prolong bursts. Here we demonstrate that Sr(2+) substitution prolongs spontaneous bursts in the disinhibited adult CA3 hippocampal slices to 37.2 +/- 7.6 (SE) times the duration in control conditions. Sr(2+) also decreased the probability of burst initiation and the rate of burst onset, consistent with reduced synchrony of glutamate release and a consequent reduced rate of spread of excitation through the slice. These findings support the supply of releasable glutamate as an important determinant of the probability and duration of synchronous CA3 network activity.}, Author = {Jones, Jethro and Stubblefield, Elizabeth A. and Benke, Timothy A. and Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:24 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {in vitro;Dose-Response Relationship, Drug;Animals;Rats;Glutamic Acid;21 Epilepsy;Periodicity;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Calcium;Male;Strontium;Nerve Net;Action Potentials;21 Neurophysiology;Picrotoxin;GABA Antagonists;21 Cortical oscillations;24 Pubmed search results 2008;Excitatory Postsynaptic Potentials}, Month = {5}, Nlm_Id = {0375404}, Number = {5}, Organization = {VBK 910, Neurology Department, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114. kstaley\@partners.org).}, Pages = {3812-8}, Pii = {01310.2006}, Pubmed = {17344368}, Title = {Desynchronization of Glutamate Release Prolongs Synchronous CA3 Network Activity}, Uuid = {6D113FD7-A8B1-46EB-A7A7-4288F2392572}, Volume = {97}, Year = {2007}, url = {papers/Jones_JNeurophysiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.01310.2006}} @article{Jones:2003, Abstract = {Increased expression of certain extracellular matrix (ECM) molecules after CNS injury is believed to restrict axonal regeneration. The chondroitin sulfate proteoglycans (CSPGs) are one such class of ECM molecules that inhibit neurite outgrowth in vitro and are upregulated after CNS injury. We examined growth responses of several classes of axons to this inhibitory environment in the presence of a cellular fibroblast bridge in a spinal cord lesion site and after a growth factor stimulus at the lesion site (fibroblasts genetically modified to secrete NGF). Immunohistochemical analysis showed dense labeling of the CSPGs NG2, brevican, neurocan, versican, and phosphacan at the host-lesion interface after spinal cord injury (SCI). Furthermore, robust expression of NG2, and to a lesser extent versican, was also observed throughout grafts of control and NGF-secreting fibroblasts. Despite this inhibitory milieu, several axonal classes penetrated control fibroblast grafts, including dorsal column sensory, rubrospinal, and nociceptive axons. Axon growth was amplified more in the presence of NGF-secreting grafts. Confocal microscopy demonstrated that axon growth was, paradoxically, preferentially associated with NG2-rich substrates in both graft types. NG2 expression also increased after sciatic nerve injury, wherein axons successfully regenerate. Cellular sources of NG2 in SCI and peripheral nerve lesion sites included Schwann cells and endothelial cells. Notably, these same cellular sources in lesion sites produced the cell adhesion molecules L1 and laminin, and these molecules all colocalized. Thus, axons grow along substrates coexpressing both inhibitory and permissive molecules, suggesting that regeneration is successful when local permissive signals balance and exceed inhibitory signals. 1529-2401 Journal Article}, Author = {Jones, L. L. and Sajed, D. and Tuszynski, M. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci}, Keywords = {Axons/drug effects/*physiology;Extracellular Matrix/metabolism;Cell Adhesion Molecules/biosynthesis;Nerve Regeneration/*physiology;Animals;Antigens/biosynthesis;Cells, Cultured;Rats;Nerve Growth Factor/biosynthesis/genetics/pharmacology;Sciatic Neuropathy/pathology/physiopathology;Female;Fibroblasts/cytology/metabolism/transplantation;Proteochondroitin Sulfates/biosynthesis/*metabolism;11 Glia;Disease Models, Animal;Support, Non-U.S. Gov't;Endothelium, Vascular/cytology/metabolism;Rats, Inbred F344;Cell Division/physiology;Spinal Cord Injuries/pathology/*physiopathology;Laminin/metabolism;Proteoglycans/biosynthesis;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Spinal Cord/metabolism/pathology;Graft Survival;Schwann Cells/cytology/metabolism;G pdf}, Number = {28}, Organization = {Department of Neurosciences, University of California-San Diego, La Jolla, California 92093, USA.}, Pages = {9276-88}, Pubmed = {14561854}, Title = {Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition}, Uuid = {C17C4CB8-2102-4AF9-AC2B-638BD58BCBAF}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14561854}} @article{Jones:1993, Abstract = {To determine whether ecotropic murine leukemia virus (MuLV) envelope glycoproteins are sufficient to cause cell-to-cell fusion when expressed in the absence of virus production, we used an ecotropic MuLV, AKV, to construct env expression vectors that lack the gag and pol genes. The rat cell line XC, which undergoes cell-to-cell fusion upon infection with ecotropic MuLV, was transfected with wild-type env expression vectors, and high levels of syncytium formation resulted. Transfection of the murine cell line NIH 3T3 with expression vectors containing the wild-type or mutated env region did not result in syncytium formation. Immunoprecipitation analysis of the envelope glycoproteins expressed in NIH 3T3 and XC cells showed that the mature surface glycoprotein expressed in XC cells was of a much lower apparent molecular weight than that expressed in NIH 3T3 cells. Further characterization showed that most if not all of this difference was the result of differences in glycosylation. Finally, site-directed mutagenesis was used to introduce several conservative and nonconservative changes into the amino-terminal region of the transmembrane protein. Analysis of the effect of these mutations confirmed that this region is a fusion domain.}, Author = {Jones, J. S. and Risser, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Viral Fusion Proteins;Animals;Recombinant Proteins;15 Retrovirus mechanism;Cell Fusion;Glycosylation;Protein Structure, Secondary;Viral Envelope Proteins;Research Support, U.S. Gov't, P.H.S.;3T3 Cells;Protein Processing, Post-Translational;Mice;AKR murine leukemia virus;DNA Mutational Analysis;Amino Acid Sequence;Mutagenesis, Site-Directed;Viral Matrix Proteins;24 Pubmed search results 2008;Molecular Sequence Data}, Medline = {93100857}, Month = {1}, Nlm_Id = {0113724}, Number = {1}, Organization = {McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.}, Pages = {67-74}, Pubmed = {8416389}, Title = {Cell fusion induced by the murine leukemia virus envelope glycoprotein}, Uuid = {020678A8-4327-11DB-A5D2-000D9346EC2A}, Volume = {67}, Year = {1993}, url = {papers/Jones_JVirol1993.pdf}} @article{Jones:2004, Abstract = {Precise timing of mitosis is essential for high-fidelity cell duplication. However, temporal measurements of the mitotic clock have been challenging. Here we present a fluorescent mitosis biosensor that monitors the time between nuclear envelope breakdown (NEB) and re-formation using parallel total internal reflection fluorescence (TIRF) microscopy. By tracking tens to hundreds of mitotic events per experiment, we found that the mitotic clock of unsynchronized rat basophilic leukemia cells has a marked precision with 80\%of cells completing mitosis in 32 +/- 6 min. This assay further allowed us to observe delays in mitotic timing at Taxol concentrations 100 times lower than previous minimal effective doses, explaining why Taxol is clinically active at low concentrations. Inactivation of the spindle checkpoint by targeting the regulator Mad2 with RNAi consistently shortened mitosis, providing direct evidence that the internal mitotic timing mechanism is much faster in cells that lack the checkpoint.}, Author = {Jones, Joshua T. and Myers, Jason W. and Ferrell, James E. and Meyer, Tobias}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {Image Interpretation, Computer-Assisted;Cell Culture;Rats;Comparative Study;Cell Line;Microscopy, Video;validation studies;evaluation studies;Biosensing Techniques;Microscopy, Fluorescence;Mitosis;Equipment Failure Analysis;Animals;Support, Non-U.S. Gov't;Cell Nucleus;23 Technique;Equipment Design}, Month = {3}, Nlm_Id = {9604648}, Number = {3}, Organization = {Department of Molecular Pharmacology, W200 Clark, 318 Campus Drive, Stanford University Medical School, Stanford, California 94305, USA.}, Pages = {306-12}, Pii = {nbt941}, Pubmed = {14990952}, Title = {Probing the precision of the mitotic clock with a live-cell fluorescent biosensor}, Uuid = {BBCF2F8E-1301-45DD-93A8-1B0AD2662908}, Volume = {22}, Year = {2004}, url = {papers/Jones_NatBiotechnol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt941}} @article{Jones:2005a, Abstract = {Decision-making requires the coordinated activity of diverse brain structures. For example, in maze-based tasks, the prefrontal cortex must integrate spatial information encoded in the hippocampus with mnemonic information concerning route and task rules in order to direct behavior appropriately. Using simultaneous tetrode recordings from CA1 of the rat hippocampus and medial prefrontal cortex, we show that correlated firing in the two structures is selectively enhanced during behavior that recruits spatial working memory, allowing the integration of hippocampal spatial information into a broader, decision-making network. The increased correlations are paralleled by enhanced coupling of the two structures in the 4- to 12-Hz theta-frequency range. Thus the coordination of theta rhythms may constitute a general mechanism through which the relative timing of disparate neural activities can be controlled, allowing specialized brain structures to both encode information independently and to interact selectively according to current behavioral demands.}, Author = {Jones, Matthew W. and Wilson, Matthew A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {Theta Rhythm;research support, non-u.s. gov't;21 Neurophysiology;Hippocampus;Prefrontal Cortex;Rats;Rats, Long-Evans;Space Perception;Time Factors;Memory;research support, n.i.h., extramural;Animals;Male;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {101183755}, Number = {12}, Organization = {The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, RIKEN-MIT Neuroscience Research Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.}, Pages = {e402}, Pii = {05-PLBI-RA-0687R2}, Pubmed = {16279838}, Title = {Theta rhythms coordinate hippocampal-prefrontal interactions in a spatial memory task}, Uuid = {14406351-BCFE-4D93-B41D-D36F7ACD4123}, Volume = {3}, Year = {2005}, url = {papers/Jones_PLoSBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0030402}} @article{Jongstra:1981, Abstract = {In contrast to those of many other mouse strains, spleen cell cultures of 129/J mice do not release reverse transcriptase activity into the supernatant upon stimulation with bacterial lipopolysaccharide. We report here that lipopolysaccharide induced the expression of intracellular viral proteins in 129/J spleen cells. Furthermore, we found that stimulated spleen cells released retroviral particles. We conclude that 129/J mice are inducible with lipopolysaccharide but that the virus produced is a defective particle deficient in reverse transcriptase activity.}, Author = {Jongstra, J. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {15 ERVs retroelements;Lipopolysaccharides;Animals;RNA-Directed DNA Polymerase;Retroviridae;Lymphocytes;Defective Viruses;Viral Proteins;15 Retrovirus mechanism;Cells, Cultured;Mice;24 Pubmed search results 2008;Lymphocyte Activation;Antigens, Viral}, Medline = {81194905}, Month = {3}, Nlm_Id = {0113724}, Number = {3}, Pages = {1044-50}, Pubmed = {6164797}, Title = {Lipopolysaccharide induces retroviral antigen expression in 129/J mouse lymphocytes: evidence for assembly of a defective viral particle}, Uuid = {BE00E952-48FB-405D-B44A-1F6BA00D4B6D}, Volume = {37}, Year = {1981}} @article{Juan:1996, Abstract = {It was observed before that DNA in situ in chromatin of mitotic cells is more sensitive to denaturation than DNA in chromatin of interphase cells. DNA sensitivity to denaturation, in these studies, was analyzed by exposing cells to heat or acid and using acridine orange (AO), the metachromatic fluorochrome which can differentially stain double-stranded (ds) vs single-stranded (ss) nucleic acids, as a marker of the degree of DNA denaturation. However, without prior cell treatment with heat or acid no presence of single-stranded DNA in either mitotic or interphase cells was detected by this assay. In the present experiments we demonstrate that DNA in situ in mitotic cells, without any prior treatment that can induce DNA denaturation, is sensitive to ss-specific S1 and mung bean nucleases. Incubation of permeabilized human T cell leukemic MOLT-4, promyelocytic HL-60, histiomonocytic lymphoma U937 cells, or normal PHA-stimulated lymphocytes with S1 or mung bean nucleases generated extensive DNA breakage in mitotic cells. DNA strand breaks were detected using fluorochrome-labeled triphosphonucleotides in the reaction catalyzed by exogenous terminal deoxynucleotidyl transferase. Under identical conditions of the cells' exposure to ss-specific nucleases, DNA breakage in interphase cells was of an order of magnitude less extensive compared to mitotic cells. The data indicate that segments of DNA in mitotic chromosomes, in contrast to interphase cells, may be in a conformation which is sensitive to ss nucleases. This may be a reflection of the differences in the torsional stress of DNA loops between interphase and mitotic chromatin. Namely, greater stress in mitotic loops may lead to formation of the hairpin-loop structures by inverted repeats; such structures are sensitive to ss nucleases. The present method of detection of such segments appears to be more sensitive than the use of AO. The identification of mitotic cells based on sensitivity of their DNA to ss nucleases provides an additional method for their quantification by flow cytometry.}, Author = {Juan, G. and Pan, W. and Darzynkiewicz, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0014-4827}, Journal = {Exp Cell Res}, Keywords = {23 dNTPs-Brdu;Fluorescent Dyes;Interphase;Chromatin;Humans;Lymphocytes;Mitosis;Aspergillus Nuclease S1;23 Technique;DNA, Single-Stranded;Research Support, U.S. Gov't, P.H.S.;Tumor Cells, Cultured;Leukemia, Promyelocytic, Acute;Flow Cytometry;Nucleic Acid Denaturation;Uridine Triphosphate;24 Pubmed search results 2008;Bromodeoxyuridine;DNA Fragmentation;Research Support, Non-U.S. Gov't}, Medline = {96428453}, Month = {9}, Nlm_Id = {0373226}, Number = {2}, Organization = {Cancer Research Institute, New York Medical College, Valhalla 10595, USA.}, Pages = {197-202}, Pii = {S0014482796902670}, Pubmed = {8831556}, Title = {DNA segments sensitive to single-strand-specific nucleases are present in chromatin of mitotic cells}, Uuid = {6003D77A-B17A-465C-8990-004D63E3FE29}, Volume = {227}, Year = {1996}, url = {papers/Juan_ExpCellRes1996.pdf}} @article{Julien:1974, Author = {Julien, R. M. and Laxer, K. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0013-4694}, Journal = {Electroencephalogr Clin Neurophysiol}, Keywords = {Penicillins;Epilepsy;Purkinje Cells;Electroencephalography;Cerebellar Cortex;21 Neurophysiology;Cats;21 Epilepsy;Neural Pathways;Disease Models, Animal;Animals;Cerebral Cortex;Cerebellar Nuclei;24 Pubmed search results 2008}, Medline = {74266348}, Month = {8}, Nlm_Id = {0375035}, Number = {2}, Pages = {123-32}, Pubmed = {4135018}, Title = {Cerebellar responses to penicillin-induced cerebral cortical epileptiform discharge}, Uuid = {E5869FA4-882E-45BE-BDE7-185C56C61E5C}, Volume = {37}, Year = {1974}} @article{Julius:2004, Author = {Julius, David and Katz, Lawrence C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {13 Olfactory bulb anatomy}, Month = {12}, Nlm_Id = {0413066}, Number = {6}, Organization = {Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143 USA.}, Pages = {747-52}, Pii = {S0092867404011638}, Pubmed = {15607972}, Title = {A nobel for smell}, Uuid = {252D01F5-60A0-4B78-A320-F1F16FF8891D}, Volume = {119}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.12.004}} @article{Jun:2007, Abstract = {Temporally precise sequences of neuronal spikes that span hundreds of milliseconds are observed in many brain areas, including songbird premotor nucleus, cat visual cortex, and primary motor cortex. Synfire chains-networks in which groups of neurons are connected via excitatory synapses into a unidirectional chain-are thought to underlie the generation of such sequences. It is unknown, however, how synfire chains can form in local neural circuits, especially for long chains. Here, we show through computer simulation that long synfire chains can develop through spike-time dependent synaptic plasticity and axon remodeling-the pruning of prolific weak connections that follows the emergence of a finite number of strong connections. The formation process begins with a random network. A subset of neurons, called training neurons, intermittently receive superthreshold external input. Gradually, a synfire chain emerges through a recruiting process, in which neurons within the network connect to the tail of the chain started by the training neurons. The model is robust to varying parameters, as well as natural events like neuronal turnover and massive lesions. Our model suggests that long synfire chain can form during the development through self-organization, and axon remodeling, ubiquitous in developing neural circuits, is essential in the process.}, Author = {Jun, Joseph K. and Jin, Dezhe Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1932-6203}, Journal = {PLoS ONE}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Nlm_Id = {101285081}, Number = {1}, Organization = {Department of Physics, The Pennsylvania State University, University Park, Pennsylvania, United States of America.}, Pages = {e723}, Pubmed = {17684568}, Title = {Development of neural circuitry for precise temporal sequences through spontaneous activity, axon remodeling, and synaptic plasticity}, Uuid = {1460447A-6D3C-44C8-BA14-435BD5DC829F}, Volume = {2}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0000723}} @article{Jung:2000, Abstract = {The seven-transmembrane receptor CX(3)CR1 is a specific receptor for the novel CX(3)C chemokine fractalkine (FKN) (neurotactin). In vitro data suggest that membrane anchoring of FKN, and the existence of a shed, soluble FKN isoform allow for both adhesive and chemoattractive properties. Expression on activated endothelium and neurons defines FKN as a potential target for therapeutic intervention in inflammatory conditions, particularly central nervous system diseases. To investigate the physiological function of CX(3)CR1-FKN interactions, we generated a mouse strain in which the CX(3)CR1 gene was replaced by a green fluorescent protein (GFP) reporter gene. In addition to the creation of a mutant CX(3)CR1 locus, this approach enabled us to assign murine CX(3)CR1 expression to monocytes, subsets of NK and dendritic cells, and the brain microglia. Analysis of CX(3)CR1-deficient mice indicates that CX(3)CR1 is the only murine FKN receptor. Yet, defying anticipated FKN functions, absence of CX(3)CR1 interferes neither with monocyte extravasation in a peritonitis model nor with DC migration and differentiation in response to microbial antigens or contact sensitizers. Furthermore, a prominent response of CX(3)CR1-deficient microglia to peripheral nerve injury indicates unimpaired neuronal-glial cross talk in the absence of CX(3)CR1.}, Author = {Jung, S. and Aliberti, J. and Graemmel, P. and Sunshine, M. J. and Kreutzberg, G. W. and Sher, A. and Littman, D. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0270-7306}, Journal = {Mol Cell Biol}, Keywords = {Receptors, Cytokine;Luminescent Proteins;Receptors, HIV;Mutagenesis, Insertional;Research Support, Non-U.S. Gov't;Phenotype;Gene Expression;Mice, Mutant Strains;11 Glia;Gene Targeting;Green Fluorescent Proteins;Mice;Genes, Reporter;Animals}, Medline = {20266298}, Month = {6}, Nlm_Id = {8109087}, Number = {11}, Organization = {Skirball Institute of Biomolecular Medicine and Howard Hughes Medical Institute New York University Medical Center, New York, New York 10016, USA. jung\@saturn.med.nyu.edu}, Pages = {4106-14}, Pubmed = {10805752}, Title = {Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion}, Uuid = {03D24E18-43DD-4A75-A408-600AF9B50F9C}, Volume = {20}, Year = {2000}, url = {papers/Jung_MolCellBiol2000.pdf}} @article{Justice:2003, Abstract = {The tumor suppressor genes lethal giant larvae (lgl) and discs large (dlg) act together to maintain the apical basal polarity of epithelial cells in the Drosophila embryo. Neuroblasts that delaminate from the embryonic epithelium require lgl to promote formation of a basal Numb and Prospero crescent, which will be asymmetrically segregated to the basal daughter cell upon division to specify cell fate. Sensory organ precursors (SOPs) also segregate Numb asymmetrically at cell division. Numb functions to inhibit Notch signaling and to specify the fates of progenies of the SOP that constitute the cellular components of the adult sensory organ. We report here that, in contrast to the embryonic neuroblast, lgl is not required for asymmetric localization of Numb in the dividing SOP. Nevertheless, mosaic analysis reveals that lgl is required for cell fate specification within the SOP lineage; SOPs lacking Lgl fail to specify internal neurons and glia. Epistasis studies suggest that Lgl acts to inhibit Notch signaling by functioning downstream or in parallel with Numb. These findings uncover a previously unknown function of Lgl in the inhibition of Notch and reveal different modes of action by which Lgl can influence cell fate in the neuroblast and SOP lineages. 0960-9822 Journal Article}, Author = {Justice, N. and Roegiers, F. and Jan, L. Y. and Jan, Y. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Curr Biol}, Keywords = {10 Development;F}, Number = {9}, Organization = {Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco, 533 Parnassus Avenue, San Francisco, CA 94143-0725, USA.}, Pages = {778-83}, Pubmed = {12725738}, Title = {Lethal giant larvae acts together with numb in notch inhibition and cell fate specification in the Drosophila adult sensory organ precursor lineage}, Uuid = {13D321DA-99E3-46CB-B4F2-3BA2451ADB39}, Volume = {13}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12725738}} @article{Kaas:1999, Abstract = {0028-0836 News}, Author = {Kaas, J. H. and Reiner, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Nature}, Keywords = {Human;*Neocortex/cytology/physiology;N;Neurons/physiology;*Evolution;Animals;19 Neocortical evolution}, Number = {6735}, Pages = {418-9}, Pubmed = {10365953}, Title = {Evolutionary neurobiology. The neocortex comes together}, Uuid = {FCEA8A34-5316-410C-962E-65E735174CBC}, Volume = {399}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10365953}} @article{Kacza:1997, Abstract = {OBJECTIVES AND METHODS: A fluorescence and electron microscopical approach, based on the transection of the rat optic nerve and the axotomy-induced transcellular labelling of activated retinal microglial cells, using the carbocyanine dye 4Di-10ASP, was employed to monitor phagocytosis in the injured central nervous system. After survival times ranging between two days up to three months, retinal flat-mounts were inspected and photoconverted. RESULTS: Fluorescence microscopy revealed that within a few days microglia became transcellularly stained due to the phagocytosed 4Di-10ASP-labelled neuronal debris. Ultrastructural analysis confirmed that marked ganglion cell-derived material was incorporated into phagosomes of various sizes. Though immediate phagocytic intake was not observed, the nature of the detected phagosomes suggests that small fractions of degenerated neurons are incorporated. CONCLUSIONS: The approach presented, utilizing function-dependent transcellular fluorescent labelling of phagocytic microglia, might enrich further experimental studies of glia-neuron interactions in the injured nervous system.}, Author = {Kacza, J. and Seeger, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {1023-3830}, Journal = {Inflamm Res}, Keywords = {Retina;Cell Membrane;Neuroglia;Nerve Degeneration;Rats;Microscopy, Electron;Phagocytes;Not relevant;11 Glia;Microscopy, Fluorescence;Optic Nerve;Retinal Ganglion Cells;Support, Non-U.S. Gov't;Animals;Axotomy}, Medline = {98039588}, Month = {10}, Nlm_Id = {9508160}, Number = {10}, Organization = {Institute of Veterinary Anatomy, University of Leipzig, Germany. kacza\@vetmed.uni-leipzig.de}, Pages = {430-3}, Pubmed = {9372319}, Title = {Transcellular labelling of activated retinal microglia following transection of the optic nerve}, Uuid = {29F1FFB2-31AE-45FA-A67C-F450A418284E}, Volume = {46}, Year = {1997}} @article{Kafitz:2008, Abstract = {The reliable identification of astrocytes for physiological measurements was always time-consuming and difficult. Recently, the fluorescent dye sulforhodamine 101 (SR101) was reported to label cortical glial cells in vivo [Nimmerjahn A, Kirchhoff F, Kerr JN, Helmchen F. Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo. Nat Methods 2004;1:31-7]. We adapted this technique for use in acute rat hippocampal slices at early postnatal stages (P3, 7, 15) and in young adults (P24-27) and describe a procedure for double-labeling of SR101 and ion-selective dyes. Using whole-cell patch-clamp, imaging, and immunohistochemistry, we characterized the properties of SR101-positive versus SR101-negative cells in the stratum radiatum. Our data show that SR101, in contrast to Fura-2 or SBFI, only stains a subset of glial cells. Throughout development, SR101-positive and SR101-negative cells differ in their basic membrane properties. Furthermore, SR101-positive cells undergo a developmental switch from variably rectifying to passive between P3 and P15 and lack voltage-gated Na+ currents. At P15, the majority of SR101-positive cells is positive for GFAP. Thus, our data demonstrate that SR101 selectively labels a subpopulation of glial cells in early juvenile hippocampi that shows the typical developmental changes and characteristics of classical astrocytes. Owing to its reliability and uncomplicated handling, we expect that this technique will be helpful in future investigations studying astrocytes in the developing brain.}, Author = {Kafitz, Karl Wolfgang and Meier, Silke Doris and Stephan, Jonathan and Rose, Christine Rosemarie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Fura-2;Coloring Agents;Rhodamines;Electrophysiology;Benzofurans;Calcium Signaling;Animals;Rats;Sodium Channels;Fluorescent Dyes;Patch-Clamp Techniques;Cell Membrane;Cytological Techniques;Hippocampus;Staining and Labeling;Ethers, Cyclic;research support, non-u.s. gov't;Organ Culture Techniques;Animals, Newborn;Neuroglia;Membrane Potentials;Neurophysiology;24 Pubmed search results 2008;Immunohistochemistry;Glial Fibrillary Acidic Protein}, Month = {3}, Nlm_Id = {7905558}, Number = {1}, Organization = {Institut f{\"u}r Neurobiologie, Heinrich-Heine-Universit{\"a}t D{\"u}sseldorf, Universit{\"a}tsstrasse 1, D-40225 D{\"u}sseldorf, Germany. kafitz\@uni-duesseldorf.de}, Pages = {84-92}, Pii = {S0165-0270(07)00594-8}, Pubmed = {18187203}, Title = {Developmental profile and properties of sulforhodamine 101--Labeled glial cells in acute brain slices of rat hippocampus}, Uuid = {F27D5BD8-9209-4F6D-8B18-CCFD0085C356}, Volume = {169}, Year = {2008}, url = {papers/Kafitz_JNeurosciMethods2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2007.11.022}} @article{Kageyama:2000, Abstract = {For embryos that have small pancreas and lack brain, eyes and thymus, the defects are caused by mutation of a single gene, Hes1. Hes1 encodes a basic helix-loop-helix (bHLH) transcriptional repressor and functionally antagonizes positive bHLH genes such as the neuronal determination gene, Mash1. Misexpression of Hes1 inhibits cell differentiation and keeps cells at the precursor stage or proliferative stage. Conversely, in the absence of Hes1, the expression of positive bHLH genes is upregulated and cells differentiate prematurely without sufficient cell growth. As a result, the development of many tissues such as the brain, eye and pancreas is severely affected. Thus, Hes1 regulates tissue morphogenesis by maintaining undifferentiated cells. In the case of T cell development, Hes1 mutation leads to defects of expansion of early T cell precursors and thereby suppresses T cell fate specification. Thus, Hes1 promotes differentiation of some cell types in addition to maintenance of the undifferentiated state. Interestingly, Hes1 expression is controlled by the transmembrane protein Notch, which is activated by the ligands expressed on the surface of neighboring cells. Taken together, these results indicate that the Notch-Hes1 pathway, which is controlled by cell-cell interaction, plays an essential role in differentiation of many cell types.}, Author = {Kageyama, R. and Ohtsuka, T. and Tomita, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Mol Cells}, Keywords = {Muscle Proteins/genetics/*physiology;Nervous System/cytology;T-Lymphocytes/cytology;Sequence Homology, Amino Acid;Molecular Sequence Data;Human;Transcription Factors/genetics/*physiology;Endocrine System/cytology;Animal;Amino Acid Sequence;04 Adult neurogenesis factors;Muscles/cytology;Exocrine Glands/cytology;Support, Non-U.S. Gov't;DNA-Binding Proteins/genetics/*physiology;Cell Differentiation/physiology;C abstr}, Number = {1}, Organization = {Institute for Virus Research, Kyoto University, Japan. rkageyam\@virus.kyoto-u.ac.jp}, Pages = {1-7.}, Title = {The bHLH gene Hes1 regulates differentiation of multiple cell types}, Uuid = {F5F46DA0-8457-4B8A-8BCA-D5FC720E8618}, Volume = {10}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10774739}} @article{Kaiser:2001, Abstract = {1. Bitufted interneurons in layer 2/3 of the rat (P14) somatosensory cortex have elongated apical and basal dendritic arbors that can span the entire depth of the cortex. Simultaneous dendritic and somatic whole-cell voltage recordings combined with Ca2+ fluorescence measurements were made to quantify voltage and Ca2+ signalling in dendritic arbors of bitufted neurons. 2. Action potentials (APs) initiated close to the soma by brief current injection back-propagated into the apical and basal dendritic arbors and evoked a transient increase in volume-averaged dendritic Ca2+ concentration (Delta[Ca(2+)](i)) of about 140 nM peak amplitude per AP. The AP evoked Ca2+ signal decayed with a time constant of about 200 ms. 3. A relatively high endogenous Ca(2+) binding ratio of approximately 285 determines the comparatively small rise in [Ca(2+)](i) of bitufted cell dendrites evoked by a back-propagating AP. 4. The [Ca(2+)](i) transient evoked by back-propagating dendritic APs decreased with distance (< or = 50 microm) from the soma in some neurons. At distances greater than 50 microm transients did not show a spatial gradient between the proximal and distal dendritic branches. 5. During trains of APs the mean amplitude of the steady-state increase in dendritic [Ca(2+)](i) encoded the AP frequency linearly up to 40 Hz with a slope of 20 nM Hz(-1). 6. The results suggest that APs initiated in the axon of bitufted neurons back-propagate and 'copy' the pattern of the axon's electrical activity also to the dendritic arbor. The AP pattern is transduced into a transient rise of dendritic [Ca(2+)](i) which, presumably, can regulate the receptive properties of the dendritic arbor for synaptic input. 7. Bitufted interneurons in layer 2/3 of the rat (P14) somatosensory cortex have elongated apical and basal dendritic arbors that can span the entire depth of the cortex. Simultaneous dendritic and somatic whole-cell voltage recordings combined with Ca2+ fluorescence measurements were made to quantify voltage and Ca2+ signalling in dendritic arbors of bitufted neurons. 8. Action potentials (APs) initiated close to the soma by brief current injection back-propagated into the apical and basal dendritic arbors and evoked a transient increase in volume-averaged dendritic Ca2+ concentration (Delta[Ca(2+)](i)) of about 140 nM peak amplitude per AP. The AP evoked Ca2+ signal decayed with a time constant of about 200 ms. 9. A relatively high endogenous Ca2+ binding ratio of approximately 285 determines the comparatively small rise in [Ca(2+)](i) of bitufted cell dendrites evoked by a back-propagating AP. 10. The [Ca(2+)](i) transient evoked by back-propagating dendritic APs decreased with distance (< or = 50 microm) from the soma in some neurons. At distances greater than 50 microm transients did not show a spatial gradient between the proximal and distal dendritic branches. 11. During trains of APs the mean amplitude of the steady-state increase in dendritic [Ca(2+)](i) encoded the AP frequency linearly up to 40 Hz with a slope of 20 nM Hz(-1). 12. The results suggest that APs initiated in the axon of bitufted neurons back-propagate and also 'copy' the pattern of the axon's electrical activity to the dendritic arbor. The AP pattern is transduced into a transient rise of dendritic [Ca(2+)](i) which, presumably, can regulate the receptive properties of the dendritic arbor for synaptic input.}, Author = {Kaiser, K. M. and Zilberter, Y. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Tissue Distribution;Calcium Signaling;Animals;Osmolar Concentration;Rats;Axons;in vitro ;Rats, Wistar;Tetrodotoxin;Calcium;21 Calcium imaging;Dendrites;Action Potentials;21 Neurophysiology;Sodium Channel Blockers;Somatosensory Cortex;Interneurons;24 Pubmed search results 2008;Buffers}, Month = {8}, Nlm_Id = {0266262}, Number = {Pt 1}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut f{\"u}r medizinische Forschung, Jahnstrasse 29, D-69120 Heidelberg, Germany. kaiser\@mpimf-heidelberg.mpg.de}, Pages = {17-31}, Pii = {PHY_11859}, Pubmed = {11507155}, Title = {Back-propagating action potentials mediate calcium signalling in dendrites of bitufted interneurons in layer 2/3 of rat somatosensory cortex}, Uuid = {8350A427-92C5-4597-9B5F-4924051ADEA4}, Volume = {535}, Year = {2001}, url = {papers/Kaiser_JPhysiol2001.pdf}} @article{Kakita:2001, Abstract = {The postnatal subventricular zone (SVZ) gives rise to many of the glial cells in the forebrain. We investigated migration pathways and dynamics of motility of progenitors from the neonatal rat forebrain SVZ by labeling progenitors in vivo with a retrovirus encoding green fluorescent protein (GFP) and then visualizing the dynamics of their movements by time-lapse fluorescence microscopy in slice preparations. Cells within the dorso-lateral SVZ moved in an apparently undirected fashion, but migrated in a directed manner after emigration into white matter and cortex, displaying both radial and tangential migration. Cells in the striatal-SVZ, a region of SVZ along the lateral wall of the ventricle, migrated parallel to the ventricular surface, and entered the striatum, where they migrated both perpendicular and parallel to the ventricular surface. Sometimes, cells in all these regions reversed their migration back toward the SVZ. Migration involved either elongation of the leading process followed by a quick translocation of the nucleus or a synchronous advancement of the nucleus and the leading process. Two distinct patterns of cellular changes were observed at orthogonal turning: one involves the cessation of cell body movement and the formation of a new leading process, and the other involves continuous cell body movement and bending of the leading process. The dynamic behavior of progenitors may reflect local tissue architecture and contribute to the widespread distribution of glia.}, Author = {Kakita, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Hum Cell}, Keywords = {G abstr;11 Glia}, Number = {1}, Organization = {Department of Pathology, Brain Disease Research Center, Brain Research Institute, Niigata University. kakita\@bri.niigata-u.ac.jp}, Pages = {59-75.}, Title = {Migration pathways and behavior of glial progenitors in the postnatal forebrain}, Uuid = {7F14D824-14ED-48F3-B9ED-95E85086F394}, Volume = {14}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11436354}} @article{Kakita:2003, Abstract = {Transplacental administration of methylmercury (MeHg) induces disruption of neuronal migration in the developing cerebral cortex. However, the effects of MeHg on glial progenitor migration remain unclear. To understand this, we performed double administration of MeHg and 5-bromo-2-deoxyuridine (BrdU) to neonatal rat pups on postnatal day 2 (P2), when glial cells are generated from progenitors in the subventricular zone (SVZ). Histopathological examination of a proportion of the MeHg-treated rats on P28 revealed no apparent abnormalities of cytoarchitecture or neuron count in either the primary motor or primary somatosensory cortex of the cerebrum. BrdU immunohistochemistry revealed abnormal accumulation of the labeled cells in the deeper layers of the cortices and underlying white matter of both areas, where an excessive number of astrocytes (glial fibrillary acidic protein- or S-100beta-immunolabeled cells) and oligodendrocytes (2',3'-cyclic-nucleotide 3'-phosphohydrolase-labeled cells) were located. Next, to investigate the migration of individual progenitors from the forebrain SVZ of P2 neonates, we labeled them in vivo with a retrovirus encoding green fluorescent protein (GFP), following administration of MeHg, and then examined the distribution pattern of the GFP-labeled cells in the P28 cerebrum. We found that the labeled cells developed into astrocytes and oligodendrocytes and were accumulated abnormally in the lateral white matter as well as in the adjacent deeper layer of the lateral cortex and lateral side of the striatum. Thus, exposure to MeHg in the gliogenic period induced irregular distribution of glia as a consequence of abnormal migration of the postnatal progenitors.}, Author = {Kakita, Akiyoshi and Inenaga, Chikanori and Sakamoto, Mineshi and Takahashi, Hitoshi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Research Support, Non-U.S. Gov't;Tissue Distribution;Animals;Kidney;Aging;Rats;Comparative Study;Cell Count;Telencephalon;Cell Movement;Liver;Rats, Wistar;Nerve Growth Factors;Animals, Newborn;Methylmercury Compounds;Neuroglia;Neurons;Cerebellum;24 Pubmed search results 2008;Bromodeoxyuridine;Stem Cells;S100 Proteins;Brain Stem;Glial Fibrillary Acidic Protein}, Medline = {22865166}, Month = {8}, Nlm_Id = {2985192R}, Number = {8}, Organization = {Department of Pathological Neuroscience, Resource Branch for Brain Disease Research CBBR, Brain Research Institute, Niigata University, Asahimachi, Niigata, Japan. kakita\@bri.niigata-u.ac.jp}, Pages = {835-47}, Pubmed = {14503639}, Title = {Disruption of postnatal progenitor migration and consequent abnormal pattern of glial distribution in the cerebrum following administration of methylmercury}, Uuid = {5088C32F-81A2-4750-8253-EE9DD05F3F2C}, Volume = {62}, Year = {2003}} @article{Kakita:1999, Abstract = {Glial progenitors colonize the CNS widely in the perinatal period, but the pathways and mechanisms of migration are not well understood. We investigated the migration of progenitors from the neonatal rat forebrain subventricular zone (SVZ) by labeling them in vivo with a retrovirus encoding green fluorescent protein and visualizing movements by time lapse microscopy in slices. Cells within the dorsolateral SVZ moved in an undirected fashion but migrated radially and tangentially after emigration into white matter, cortex, and striatum. Cells in the striatal SVZ migrated parallel to the ventricular surface. During migration, elongation of the leading process and nuclear translocation were independent or linked. Orthogonal turning involved either cessation of cell body movement and formation of a new leading process or continuous cell body movement and bending of the leading process.}, Author = {Kakita, A. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Neuron}, Keywords = {Rats;Transfection;Cell Movement/*physiology;Animal;Indicators and Reagents;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Cerebral Cortex/cytology/growth &development;Retroviridae;Stem Cells/*cytology;Animals, Newborn;Prosencephalon/*cytology/*growth &development;B-17;Support, U.S. Gov't, P.H.S.;Neuroglia/*cytology;Luminescent Proteins;Organ Culture;Corpus Striatum/cytology/growth &development}, Number = {3}, Organization = {Department of Pathology and The Center for Neurobiology and Behavior, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. ak463\@columbia.edu}, Pages = {461-72.}, Title = {Patterns and dynamics of SVZ cell migration in the postnatal forebrain: monitoring living progenitors in slice preparations}, Uuid = {B59BBF33-8944-45AD-925B-95412E4FD0F7}, Volume = {23}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10433259}} @article{Kalatsky:2003, Abstract = {We present a new technique for acquiring and analyzing intrinsic signal optical images of brain activity, using continuous stimulus presentation and data acquisition. The main idea is to present a temporally periodic stimulus and to analyze the component of the response at the stimulus frequency. Advantages of the new technique include the removal of heart, respiration, and vasomotor artifacts, a dramatic increase in spatial resolution, and a 30-fold or greater reduction in acquisition time. We also present a novel approach to localizing instantaneous neuronal responses using time-reversed stimuli that is widely applicable to brain imaging. To demonstrate the power of the technique, we present high-resolution retinotopic maps of five visual areas in mouse cortex and orientation maps in cat visual cortex.}, Author = {Kalatsky, Valery A. and Stryker, Michael P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-26 13:10:06 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development;Animals;Photic Stimulation;Visual Perception;Functional Laterality;Mice, Inbred C3H;Mice, Inbred C57BL;Cerebrovascular Circulation;research support, non-u.s. gov't;Orientation;Evoked Potentials, Visual;research support, u.s. gov't, p.h.s.;Neurons;Mice;Reproducibility of Results;24 Pubmed search results 2008;Visual Cortex;Cats;Brain Mapping}, Month = {5}, Nlm_Id = {8809320}, Number = {4}, Organization = {W.M. Keck Foundation Center for Integrative Neuroscience, Department of Physiology, University of California-San Francisco, San Francisco, CA 94143, USA.}, Pages = {529-45}, Pii = {S0896627303002861}, Pubmed = {12765606}, Title = {New paradigm for optical imaging: temporally encoded maps of intrinsic signal}, Uuid = {64EB9F98-214C-47FA-94C3-18FAB200D538}, Volume = {38}, Year = {2003}, url = {papers/Kalatsky_Neuron2003.pdf}} @article{Kalberer:2000, Abstract = {Transcriptional silencing of genes transferred into hematopoietic stem cells poses one of the most significant challenges to the success of gene therapy. If the transferred gene is not completely silenced, a progressive decline in gene expression as the mice age often is encountered. These phenomena were observed to various degrees in mouse transplant experiments using retroviral vectors containing a human beta-globin gene, even when cis-linked to locus control region derivatives. Here, we have investigated whether ex vivo preselection of retrovirally transduced stem cells on the basis of expression of the green fluorescent protein driven by the CpG island phosphoglycerate kinase promoter can ensure subsequent long-term expression of a cis-linked beta-globin gene in the erythroid lineage of transplanted mice. We observed that 100\%of mice (n = 7) engrafted with preselected cells concurrently expressed human beta-globin and the green fluorescent protein in 20-95\%of their RBC for up to 9.5 mo posttransplantation, the longest time point assessed. This expression pattern was successfully transferred to secondary transplant recipients. In the presence of beta-locus control region hypersensitive site 2 alone, human beta-globin mRNA expression levels ranged from 0.15\%to 20\%with human beta-globin chains detected by HPLC. Neither the proportion of positive blood cells nor the average expression levels declined with time in transplanted recipients. Although suboptimal expression levels and heterocellular position effects persisted, in vivo stem cell gene silencing and age-dependent extinction of expression were avoided. These findings support the further investigation of this type of vector for the gene therapy of human hemoglobinopathies.}, Author = {Kalberer, C. P. and Pawliuk, R. and Imren, S. and Bachelot, T. and Takekoshi, K. J. and Fabry, M. and Eaves, C. J. and London, I. M. and Humphries, R. K. and Leboulch, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Erythrocytes;Transcription, Genetic;Animals;Globins;comment;Humans;Transfection;Mice, Inbred C3H;Mice, Inbred C57BL;Recombinant Fusion Proteins;Retroviridae;Time Factors;11 Glia;Green Fluorescent Proteins;RNA, Messenger;Mice, Inbred Strains;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Genetic Vectors;Hematopoietic Stem Cell Transplantation;Locus Control Region;Gene Silencing;Mice;Hematopoietic Stem Cells;Luminescent Proteins;Phosphoglycerate Kinase;Promoter Regions (Genetics);Research Support, Non-U.S. Gov't}, Medline = {20266379}, Month = {5}, Nlm_Id = {7505876}, Number = {10}, Organization = {The Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC, Canada Y5Z 1L3.}, Pages = {5411-5}, Pii = {100082597}, Pubmed = {10792053}, Title = {Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human beta-globin in engrafted mice}, Uuid = {01E9A09C-4F1A-473F-9DE4-A7A7D5C93C95}, Volume = {97}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.100082597}} @article{Kalisman:2005, Abstract = {The neocortex has a high capacity for plasticity. To understand the full scope of this capacity, it is essential to know how neurons choose particular partners to form synaptic connections. By using multineuron whole-cell recordings and confocal microscopy we found that axons of layer V neocortical pyramidal neurons do not preferentially project toward the dendrites of particular neighboring pyramidal neurons; instead, axons promiscuously touch all neighboring dendrites without any bias. Functional synaptic coupling of a small fraction of these neurons is, however, correlated with the existence of synaptic boutons at existing touch sites. These data provide the first direct experimental evidence for a tabula rasa-like structural matrix between neocortical pyramidal neurons and suggests that pre- and postsynaptic interactions shape the conversion between touches and synapses to form specific functional microcircuits. These data also indicate that the local neocortical microcircuit has the potential to be differently rewired without the need for remodeling axonal or dendritic arbors.}, Author = {Kalisman, Nir and Silberberg, Gilad and Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Imaging, Three-Dimensional;Microscopy, Confocal;Synapses;Dendrites;Research Support, Non-U.S. Gov't;21 Neurophysiology;Nerve Regeneration;Rats;Neocortex;Rats, Wistar;21 Circuit structure-function;Electrophysiology;Animals;24 Pubmed search results 2008;Neurons;Axons}, Month = {1}, Nlm_Id = {7505876}, Number = {3}, Organization = {Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.}, Pages = {880-5}, Pii = {0407088102}, Pubmed = {15630093}, Title = {The neocortical microcircuit as a tabula rasa}, Uuid = {45CCB041-62FA-4523-BAA9-CCEE3E489174}, Volume = {102}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0407088102}} @article{Kalman:2001, Abstract = {The present study compares the immunopositive elements in the developing rat cortex between the day of birth (P0) and the 18th postnatal day (P18), after immunostaining against nestin, vimentin and glial fibrillary acidic protein (GFAP). Nestin immunostaining revealed more structural details than either vimentin or GFAP, or they together. While vimentin immunostaining preferred radial glia and GFAP preferred astrocytes, nestin immunostaining detected both. Stellate-shaped astrocyte-like cells were already seen at P0 and cells of typical astrocytic morphology were numerous at P3, and were predominating elements from P7, whereas GFAP-immunopositive astrocytes were very scarce even at P7, and became numerous only by P11, when nestin immunopositivity started to disappear. Nestin immunostaining revealed such structures which were not seen in GFAP- or vimentin immunostained sections: cell body-like structures 'hanging'at the end the radial fibers, seeming to divide with their fibers, or having astrocyte-like processes. Nestin immunostaining is therefore highly recommended for studies of the glial architecture in the early post-natal brain development.}, Author = {Kalman, M. and Ajtai, B. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Int J Dev Neurosci}, Keywords = {11 Glia;G}, Number = {1}, Organization = {Department of Anatomy, Histology and Embryology, Semmelweis University of Medicine, Tuzolto 58, 1094, Budapest, Hungary}, Pages = {101-8.}, Title = {A comparison of intermediate filament markers for presumptive astroglia in the developing rat neocortex: immunostaining against nestin reveals more detail, than GFAP or vimentin}, Uuid = {597429B2-2785-463B-A363-87EF431D9923}, Volume = {19}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11226759}} @article{Kalman:1991, Abstract = {The majority of astroglia develop postnatally in rats. GFAP (glial fibrillary acidic protein)-immunoreactivity appears mainly during the 2nd and 3rd postnatal weeks throughout the brain. Hypothyroidism inhibits, among others, the cell proliferation, maturation, and migration of neurons. However, hardly any data on the effect of hypothyroidism on GFAP-immunoreactivity are available in the literature. In our experiments, thyroidectomy was performed between the 3rd and 5th postnatal days. Operated and control animals from the same litter were perfused transcardially and processed for immunohistochemistry in parallel after 2, 3, and 4 wk. On the basis of serial sections, the development of GFAP-immunoreactivity was not generally affected by hypothyroidism. We could observe only two phenomena that showed a tendency of retardation in the operated animals: (1) the decrease of the strong GFAP-immunopositivity of white matter tracts (for example, internal capsule and pyramidal tract) and (2) the gradual disappearance of the GFAP-immunoreactive radial fibers (for example, in the neocortex, in the olfactory bulb, and around the 3rd ventricle).}, Author = {Kalman, M. and Moskovkin, G. N. and Martinez, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Mol Chem Neuropathol}, Keywords = {Organ Specificity;Aging;*Thyroidectomy;Reference Values;Rats;Immunohistochemistry;Hypothyroidism/physiopathology;Animal;11 Glia;Glial Fibrillary Acidic Protein/*metabolism;Animals, Newborn;Immunoenzyme Techniques;G-need;Brain/cytology/*growth &development/metabolism;Astrocytes/cytology/metabolism/*physiology}, Number = {2}, Organization = {1st Dept of Anatomy, Semmelweis University of Medicine, Budapest, Hungary.}, Pages = {103-16.}, Title = {Development of glial fibrillary acidic protein immunoreactivity in thyroidectomized rats}, Uuid = {761CA0F0-E3AC-46C2-B78C-89499C7204FB}, Volume = {15}, Year = {1991}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1776989}} @article{Kaltschmidt:2000, Abstract = {The asymmetric segregation of cell-fate determinants and the generation of daughter cells of different sizes rely on the correct orientation and position of the mitotic spindle. In the Drosophila embryo, the determinant Prospero is localized basally and is segregated equally to daughters of similar cell size during epidermal cell division. In contrast, during neuroblast division Prospero is segregated asymmetrically to the smaller daughter cell. This simple switch between symmetric and asymmetric segregation is achieved by changing the orientation of cell division: neural cells divide in a plane perpendicular to that of epidermoblast division. Here, by labelling mitotic spindles in living Drosophila embryos, we show that neuroblast spindles are initially formed in the same axis as epidermal cells, but rotate before cell division. We find that daughter cells of different sizes arise because the spindle itself becomes asymmetric at anaphase: apical microtubules elongate, basal microtubules shorten, and the midbody moves basally until it is positioned asymmetrically between the two spindle poles. This observation contradicts the widely held hypothesis that the cleavage furrow is always placed midway between the two centrosomes. 20089045 1465-7392 Journal Article}, Author = {Kaltschmidt, J. A. and Davidson, C. M. and Brown, N. H. and Brand, A. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Nat Cell Biol}, Keywords = {10 Development;Stem Cells/cytology/physiology;Prophase/physiology;Nervous System/cytology/growth &development;Tubulin/analysis;Neurons/*cytology/physiology;Metaphase/physiology;Microscopy, Confocal;Phosphorylation;Rotation;Animal;Histones/analysis/metabolism;Mitotic Spindle Apparatus/chemistry/*physiology;Support, Non-U.S. Gov't;Anaphase/physiology;Drosophila/cytology/*growth &development;Epidermis/cytology/growth &development;F;Interphase/physiology}, Number = {1}, Organization = {Wellcome/CRC Institute and Department of Genetics, University of Cambridge, Tennis Court Road, Cambridge CB2 1QR, UK.}, Pages = {7-12}, Pubmed = {10620800}, Title = {Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system}, Uuid = {0CC3007C-1A17-43F8-ABAE-E007136F1ACC}, Volume = {2}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10620800}} @article{Kamei:1998, Abstract = {Although accumulating data reveal patterns of proliferation, migration, and differentiation of neuronal lineage cells in the developing brain, gliogenesis in the brain has not been well elucidated. In the rat brain, vimentin is selectively expressed in radial glia and in their progeny, not in oligodendrocytes or neurons from embryonic day 15 (E15) until postnatal day 15 (P15). Here we examined mitotic radial glial lineage cells in the rat brain E17-P7, using the monoclonal antibody 4A4, which recognizes vimentin phosphorylated by a mitosis-specific kinase, cdc2 kinase. In the neocortex, mainly radial glia in the ventricular zone, but not their progeny, underwent cell division. In contrast, not only radial glia but also various types of radial glial progeny including Bergmann glia continued to proliferate in the cerebellum. Radial glia in the neocortex divided horizontally, obliquely, and vertically against the ventricular surface. The percentage of the vertical division increased with progress in the stage of development, concurrently with the decrease of the population of horizontal divisions. Thus, the monoclonal antibody 4A4 provides an useful tool to label mitotic glia in the developing brain and revealed different patterns of gliogenesis in the neocortex and cerebellum. A possibility is discussed that the dynamics of mitotic orientation observed here may be related to the change of the pattern of gliogenesis during development.}, Author = {Kamei, Y. and Inagaki, N. and Nishizawa, M. and Tsutsumi, O. and Taketani, Y. and Inagaki, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Glia}, Keywords = {G;Protein p34cdc2/metabolism;Neuroglia/chemistry/classification/*cytology;Rats;Phosphorylation;Mitosis;Animal;Neocortex/cytology/embryology/growth &development;Cell Polarity;11 Glia;Support, Non-U.S. Gov't;Cell Lineage;Astrocytes/cytology/metabolism;Vimentin/*analysis/immunology/metabolism;Phosphoproteins/*analysis/metabolism;Cerebellum/cytology/embryology/growth &development;Protein Processing, Post-Translational;Nerve Tissue Proteins/*analysis/metabolism;Brain/*cytology/embryology/growth &development;Biological Markers;Peptide Fragments/immunology;Enzyme-Linked Immunosorbent Assay;Antibodies, Monoclonal/immunology}, Number = {3}, Organization = {Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, Japan.}, Pages = {191-9.}, Title = {Visualization of mitotic radial glial lineage cells in the developing rat brain by Cdc2 kinase-phosphorylated vimentin}, Uuid = {1164A408-E5B1-47CA-A385-AB9FB21B45F2}, Volume = {23}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9633804}} @article{Kaneko:2000, Abstract = {In situ detection of neural progenitor cells including stem-like cells is essential for studying the basic mechanisms of the generation of cellular diversity in the CNS, upon which therapeutic treatments for CNS injuries, degenerative diseases, and brain tumors may be based. We have generated rat monoclonal antibodies (Mab 14H1 and 14B8) that recognize an RNA-binding protein Musashi1, but not a Musashi1-related protein, Musashi2. The amino acid sequences at the epitope sites of these anti-Musashi1 Mabs are remarkably conserved among the human, mouse, and Xenopus proteins. Spatiotemporal patterns of Musashi1 immunoreactivity in the developing and/or adult CNS tissues of frogs, birds, rodents, and humans indicated that our anti-Musashi1 Mabs reacted with undifferentiated, proliferative cells in the CNS of all the vertebrates tested. Double or triple immunostaining of embryonic mouse brain cells in monolayer cultures demonstrated strong Musashi1 expression in Nestin(+)/RC2(+) cells. The relative number of Musashi1(+)/Nestin(+)/RC2(+) cells increased fivefold when embryonic forebrain cells were cultured to form 'neurospheres'in which stem-like cells are known to be enriched through their self-renewing mode of growth. Nestin(+)/RC2(-) cells, which included Talpha1-GFP(+) neuronal progenitor cells and GLAST(+) astroglial precursor cells, were also Musashi1(+), as were GFAP(+) astrocytes. Young neurons showed a trace of Musashi1 expression. Cells committed to the oligodendroglial lineage were Musashi(-). Musashi1 was localized to the perikarya of CNS stem-like cells and non-oligodendroglial progenitor cells without shifting to cell processes or endfeet, and is therefore advantageous for identifying each cell and counting cells in situ. 20125908 0378-5866 Journal Article}, Author = {Kaneko, Y. and Sakakibara, S. and Imai, T. and Suzuki, A. and Nakamura, Y. and Sawamoto, K. and Ogawa, Y. and Toyama, Y. and Miyata, T. and Okano, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Dev Neurosci}, Keywords = {Central Nervous System/*cytology/*embryology/metabolism;Tissue Distribution;Animal;Cytological Techniques;02 Adult neurogenesis migration;RNA-Binding Proteins/genetics/*metabolism;Amino Acid Sequence/genetics;Nerve Tissue Proteins/genetics/*metabolism;BB abstr;03 Adult neurogenesis progenitor source;Evolution;Chick Embryo;Conserved Sequence/genetics;Xenopus/embryology;Antibodies, Monoclonal;Support, Non-U.S. Gov't;Mice/embryology;Epitopes;Neurons/metabolism;Molecular Sequence Data;Stem Cells/*metabolism;Genetic Markers}, Number = {1-2}, Organization = {Division of Neuroanatomy, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine, Tokyo, Japan.}, Pages = {139-53}, Pubmed = {10657706}, Title = {Musashi1: an evolutionally conserved marker for CNS progenitor cells including neural stem cells}, Uuid = {CC6898D6-0650-4F57-A7A0-7512A1E92B35}, Volume = {22}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10657706}} @article{Kaneko:2006, Abstract = {Neurogenesis in the subgranular zone of the hippocampal dentate gyrus and olfactory bulbs continues into adulthood and has been implicated in the cognitive function of the adult brain. The basal forebrain cholinergic system has been suggested to play a role in regulating neurogenesis as well as learning and memory in these regions. Herein, we report that highly polysialylated neural cell adhesion molecule (PSA-NCAM)-positive immature cells as well as neuronal nuclei (NeuN)-positive mature neurons in the dentate gyrus and olfactory bulb express multiple acetylcholine receptor subunits and make contact with cholinergic fibers. To examine the function of acetylcholine in neurogenesis, we used donepezil (Aricept), a potent and selective acetylcholinesterase inhibitor that improves cognitive impairment in Alzheimer's disease. Intraperitoneal administrations of donepezil significantly enhanced the survival of newborn neurons, but not proliferation of neural progenitor cells in the subgranular zone or the subventricular zone of normal mice. Moreover, donepezil treatment reversed the chronic stress-induced decrease in neurogenesis. Taken together, these results suggest that activation of the cholinergic system promotes survival of newborn neurons in the adult dentate gyrus and olfactory bulb under both normal and stressed conditions.}, Author = {Kaneko, Naoko and Okano, Hideyuki and Sawamoto, Kazunobu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1356-9597}, Journal = {Genes Cells}, Keywords = {24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9607379}, Number = {10}, Organization = {Department of Physiology, Keio University School of Medicine, Tokyo 160-8582, Japan.}, Pages = {1145-59}, Pii = {GTC1010}, Pubmed = {16999735}, Title = {Role of the cholinergic system in regulating survival of newborn neurons in the adult mouse dentate gyrus and olfactory bulb}, Uuid = {BF122FB5-F258-4BBF-907B-98C4E2067C42}, Volume = {11}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1365-2443.2006.01010.x}} @article{Kaneko:2008, Abstract = {Rapid, experience-dependent plasticity in developing visual cortex is thought to be competitive. After monocular visual deprivation, the reduction in response of binocular neurons to one eye is matched by a corresponding increase to the other. Chronic optical imaging in mice deficient in TNFalpha reveals the normal initial loss of deprived-eye responses, but the subsequent increase in response to the open eye is absent. This mutation also blocks homeostatic synaptic scaling of mEPSCs in visual cortex in vitro, without affecting LTP. In monocular cortex, thought not to be subject to competition, responses in TNFalpha mutants are as reduced as in the binocular zone. Pharmacological inhibition of endogenous TNFalpha in wild-type mice phenocopies the knockout. These findings suggest that experience-dependent competition in developing visual cortex is the outcome of two distinct, noncompetitive processes, a loss of deprived-eye responses followed by an apparently homeostatic increase in responses dependent on TNFalpha signaling.}, Author = {Kaneko, Megumi and Stellwagen, David and Malenka, Robert C. and Stryker, Michael P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {21 Neurophysiology; 21 Activity-development;Excitatory Amino Acid Antagonists;Long-Term Potentiation;Animals;Neuronal Plasticity;Tumor Necrosis Factor-alpha;Patch-Clamp Techniques;Sensory Deprivation;Visual Pathways;Organ Culture Techniques;research support, non-u.s. gov't;Analysis of Variance;Animals, Newborn;Mice, Knockout;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Dominance, Ocular;Visual Cortex;in vitro}, Month = {6}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Physiology and W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA 94143-0444, USA.}, Pages = {673-80}, Pii = {S0896-6273(08)00377-2}, Pubmed = {18549780}, Title = {Tumor necrosis factor-alpha mediates one component of competitive, experience-dependent plasticity in developing visual cortex}, Uuid = {326D6C55-A94A-459D-96B5-68ABC599659B}, Volume = {58}, Year = {2008}, url = {papers/Kaneko_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.04.023}} @article{Kanmogne:2002, Abstract = {Breakdown of the blood-brain barrier is commonly seen in patients with human immunodeficiency virus (HIV)-associated dementia, despite the lack of productive HIV-infection of the brain endothelium. Through this damaged blood-brain barrier, HIV and HIV-infected monocytes/macrophages infiltrate the brain and further infect microglia and brain macrophages. Neuronal cell death and dysfunction are the underlying cause of HIV-associated dementia, but no productive HIV-infection of neurons has been documented. It is likely that secreted viral products play a major role in blood-brain barrier damage and neuronal cell death. The aim of the present study was to examine the effect of HIV-1 gp160 peptides and gp120 proteins on brain microvascular endothelial cells and neurons from both human and rats. Four of the 7 gp160 peptides tested evoked significant neurotoxicity. Two different full-length recombinant HIV gp120 proteins (HIV-1CM235 gp120 and HIV-1MN gp120) also induced neuronal and brain endothelial cell death, and concentrations as little as 1 ng/ml evoked pronounced morphological changes in these cells and marked cytotoxicity. This study suggests that HIV proteins and peptides that are shed in vivo may be directly involved in blood-brain barrier damage and neuronal cell death in HIV-associated dementia.}, Author = {Kanmogne, Georgette D. and Kennedy, R. C. and Grammas, Paula}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Fetus;Dose-Response Relationship, Drug;Endothelium, Vascular;Animals;HIV-1;Monocytes;Cells, Cultured;Rats;Humans;Research Support, Non-U.S. Gov't;HIV Envelope Protein gp160;Brain;Culture Media, Conditioned;Recombinant Fusion Proteins;11 Glia;Blood-Brain Barrier;Research Support, U.S. Gov't, P.H.S.;Peptide Fragments;Neurons;Cell Death;HIV Envelope Protein gp120;AIDS Dementia Complex}, Medline = {22317806}, Month = {11}, Nlm_Id = {2985192R}, Number = {11}, Organization = {Department of Pathology, University of Oklahoma Health Science Center, Oklahoma City 73104, USA.}, Pages = {992-1000}, Pubmed = {12430716}, Title = {HIV-1 gp120 proteins and gp160 peptides are toxic to brain endothelial cells and neurons: possible pathway for HIV entry into the brain and HIV-associated dementia}, Uuid = {56590B38-3B9D-4799-86A8-9657C4EC9B19}, Volume = {61}, Year = {2002}} @article{Kanold:2003, Abstract = {The subplate forms a transient circuit required for development of connections between the thalamus and the cerebral cortex. When subplate neurons are ablated, ocular dominance columns do not form in the visual cortex despite the robust presence of thalamic axons in layer 4. We show that subplate ablation also prevents formation of orientation columns. Visual responses are weak and poorly tuned to orientation. Furthermore, thalamocortical synaptic transmission fails to strengthen, whereas intracortical synapses are unaffected. Thus, subplate circuits are essential not only for the anatomical segregation of thalamic inputs but also for key steps in synaptic remodeling and maturation needed to establish the functional architecture of visual cortex.}, Author = {Kanold, Patrick O. and Kara, Prakash and Reid, R. Clay and Shatz, Carla J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Visual Cortex;Electric Stimulation;Animals;Synapses;Brain-Derived Neurotrophic Factor;Synaptic Transmission;Patch-Clamp Techniques;Female;Visual Pathways;Immunotoxins;Axons;Receptors, AMPA;Kainic Acid;Male;Vision;Thalamus;Evoked Potentials, Visual;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Microelectrodes;Dominance, Ocular;Cats;Geniculate Bodies;Excitatory Postsynaptic Potentials}, Month = {7}, Nlm_Id = {0404511}, Number = {5632}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {521-5}, Pii = {301/5632/521}, Pubmed = {12881571}, Title = {Role of subplate neurons in functional maturation of visual cortical columns}, Uuid = {125929C7-1837-4D6C-98EF-1D6B03A330A0}, Volume = {301}, Year = {2003}, url = {papers/Kanold_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1084152}} @article{Kaplan:1981, Abstract = {Newly formed neurons in the adult mammalian neocortex have been reported by several investigators using light microscopic radioautography, but these reports have not been confirmed by electron microscopy--probably because their rarity precludes any reasonable chance of observing these cells with electron microscopic radioautography. To overcome this problem I have used a recently developed method that allows serial thin sectioning and subsequent electron microscopic examination of plastic-embedded sections previously prepared for light microscopic radioautography. Ninety-day- old rats were injected with 4.3 microCi per gm body weight of [H3] thymidine and allowed to survive for 30 days. In the light radioautographs, labeled cells were found in layer IV of the visual cortex, and analysis of electron micrographs of selected examples of these labeled cells clearly demonstrated their neuronal nature wit synapses along their cell bodies and dendrites. In order to quantify the relative frequency of labeled neurons, the number of labeled cells seen in the light microscopic sections was expressed as a percentage of the total number of neurons found in sections through the entire thickness of the visual cortex; the percentage was 0.011\%, or about 1 in 10,000. The results of this study are in agreement with evidence of neurogenesis of granular neurons in the adult rat olfactory bulb and dentate gyrus (Kaplan and Hinds, '77). Thus, it has now been confirmed that relatively small labeled neurons and their synapses are found in at least 3 brain regions (olfactory bulb, dentate gyrus, and visual cortex) in a normal adult rodent.}, Author = {Kaplan, M. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Comp Neurol}, Keywords = {01 Adult neurogenesis general;Cell Differentiation;A-2;Neurons/cytology;Visual Cortex/cytology/*growth &development/metabolism;Microscopy, Electron;Rats;Thymidine/metabolism;Autoradiography;Animal;Support, U.S. Gov't, P.H.S.;Mitosis;Male}, Number = {2}, Pages = {323-38.}, Title = {Neurogenesis in the 3-month-old rat visual cortex}, Uuid = {5A160142-CD3D-11D9-8C77-000D9346EC2A}, Volume = {195}, Year = {1981}, url = {papers/Kaplan_JCompNeurol1981.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7251929}} @article{Kaplan:1984, Abstract = {Ultrastructural identification of mitotic neuronal precursors beneath the basal hippocampal granule cell layer was made using electron micrographs of [3H]thymidine-labeled cells. Ultrathin sections were obtained by a method that allows serial thin sectioning of reembedded sections previously prepared for light microscopic radioautography. The electron microscopic observations reported in this study reveal: (1) that a steady rate of granule cell neurogenesis occurs during the first year of a rodent's life; (2) that newly formed granule neurons in the dentate gyrus of the newborn mouse and adult rat are a result of neuroblast division; and (3) two distinct classes of mitotic cells can be identified during the peak period of postnatal neurogenesis--those with synapses on their cell bodies and processes and those with no synapses or processes.}, Author = {Kaplan, M. S. and Bell, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {10 Development;Research Support, Non-U.S. Gov't;Hippocampus;10 Hippocampus;Microscopy, Electron;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Mitosis;Animals;Mice;Mice, Inbred Strains}, Medline = {84215313}, Month = {6}, Nlm_Id = {8102140}, Number = {6}, Pages = {1429-41}, Pubmed = {6726341}, Title = {Mitotic neuroblasts in the 9-day-old and 11-month-old rodent hippocampus}, Uuid = {0317A407-AA4A-4235-A978-6324FEDB6198}, Volume = {4}, Year = {1984}} @article{Kaplan:1977, Abstract = {Three-month-old rats were injected intraperitoneally with [3H]thymidine (4.3 microcuries per gram of body weight) and allowed to survive for 30 days. Radioautography of 1-micrometer sections revealed labeled cells in the granular layers of dentate gyrus and olfactory bulb; these were confirmed as neurons by electron microscopy of reembedded 1-micrometer sections.}, Author = {Kaplan, M. S. and Hinds, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Science}, Keywords = {A;01 Adult neurogenesis general;10 Development;Rats;10 Hippocampus;Hippocampus/cytology/*growth &development/metabolism;Thymidine/metabolism;Animal;Neurons/metabolism/*physiology;Support, U.S. Gov't, P.H.S.;Age Factors;Male;Olfactory Bulb/cytology/*growth &development/metabolism}, Number = {4308}, Pages = {1092-4.}, Title = {Neurogenesis in the adult rat: electron microscopic analysis of light radioautographs}, Uuid = {5A160966-CD3D-11D9-8C77-000D9346EC2A}, Volume = {197}, Year = {1977}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=887941}} @article{Kaplan:2001, Abstract = {Introduction by the EditorOver the past few years, the classic idea that no new nerve cells are born in the adult mammalian brain has finally and conclusively been refuted by the scientific community. Yet, the first indications that neurogenesis occurs in the brain of adult mammals were obtained using light and electron microscopy over two decades ago. Why this went unrecognized is described in a personal account by the researcher who pioneered those studies: Michael Kaplan.}, Author = {Kaplan, M. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {Trends Neurosci}, Keywords = {01 Adult neurogenesis general;A pdf}, Number = {10}, Organization = {816 Frederick Road, 21228, Catonsville, MD, USA}, Pages = {617-20.}, Title = {Environment complexity stimulates visual cortex neurogenesis: death of a dogma and a research career}, Uuid = {5A160546-CD3D-11D9-8C77-000D9346EC2A}, Volume = {24}, Year = {2001}, url = {papers/Kaplan_TrendsNeurosci2001.pdf}} @article{Kapsa:2002, Abstract = {In muscle, mutant genes can be targeted and corrected directly by intramuscular (i.m.) injection of corrective DNA, or by ex vivo delivery of DNA to myogenic cells, followed by cell transplantation. Short fragment homologous replacement (SFHR) has been used to repair the exon 23 nonsense transition at the Xp21.1 dys locus in cultured cells and also, directly in tibialis anterior from male mdx mice. Whilst mdx dys locus correction can be achieved in up to 20\%of cells in culture, much lower efficiency is evident by i.m. injection. The major consideration for application of targeted gene correction to muscle is delivery throughout relevant tissues. Systemically injected bone marrow (BM)-derived cells from wt C57BL/10 ScSn mice are known to remodel mdx muscle when injected into the systemic route. Provided that non muscle-derived cell types most capable of muscle remodeling activity can be more specifically identified, isolated and expanded, cell therapy seems presently the most favorable vehicle by which to deliver gene correction throughout muscle tissues. Using wt bone marrow as a model, this study investigates systemic application of bone marrow-derived cells as potential vehicles to deliver corrected (ie wt) dys locus to dystrophic muscle. Intravenous (i.v.) and intraperitoneal (i.p.) injections of wt BM were given to lethally and sub-lethally irradiated mdx mice. Despite both i.v. and surviving i.p. groups containing wt dys loci in 100\%and less than 1\%of peripheral blood nuclei, respectively, both groups displayed equivalent levels of wt dys transcript in muscle RNA. These results suggest that the muscle remodeling activity observed in systemically injected BM cells is not likely to be found in the hemopoietic fraction.}, Author = {Kapsa, R. M. and Quigley, A. F. and Vadolas, J. and Steeper, K. and Ioannou, P. A. and Byrne, E. and Kornberg, A. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Animals;Gene Targeting;Bone Marrow Transplantation;Dystrophin;DNA;Mice, Inbred C57BL;11 Glia;Male;Bone Marrow Cells;Mice, Inbred mdx;Gene Therapy;Muscle, Skeletal;Muscular Dystrophies;Transplantation, Autologous;Mice;Injections, Intravenous;Injections, Intraperitoneal;Research Support, Non-U.S. Gov't}, Medline = {22027842}, Month = {6}, Nlm_Id = {9421525}, Number = {11}, Organization = {Melbourne Neuromuscular Research Institute, Clinical Neurosciences, St Vincent's Hospital, Fitzroy Victoria, Australia.}, Pages = {695-9}, Pubmed = {12032690}, Title = {Targeted gene correction in the mdx mouse using short DNA fragments: towards application with bone marrow-derived cells for autologous remodeling of dystrophic muscle}, Uuid = {34789CF5-97EB-4B52-96F9-F111BBB807CC}, Volume = {9}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301737}} @article{Kara:2003, Abstract = {How does a single retinal ganglion cell (RGC) affect the firing of simple cells in the visual cortex? Although much is known of the functional connections between the retina and the lateral geniculate nucleus (LGN) and between LGN and visual cortex, it is hard to infer the effect of disynaptic connections from retina to visual cortex. Most importantly, there is considerable divergence from retina to LGN, so cortical neurons might be influenced by ganglion cells through multiple feedforward pathways. We recorded simultaneously from ganglion cells in the retina and cortical simple cells in the striate cortex with overlapping receptive fields and evaluated disynaptic connections with cross-correlation analysis. In all disynaptically connected pairs, the retinal receptive field center and overlapping cortical subregion always shared the same sign (either both ON or both OFF). Connected pairs were similar in other respects, such as relative position and timing of their receptive fields, and thus obeyed the same rules of connectivity found previously for retinothalamic and thalamocortical connections. We found that a single RGC directly contributed on average to approximately 3\%of the activity of its cortical target. The relative timing of pairs of spikes from the retinal cell affected their efficacy in driving the cortical cell. When two retinal spikes were closely spaced (<10 msec), the second spike was several times more likely to drive the cortical target. The relative magnitude of this disynaptic paired spike enhancement was considerably larger than has been found previously for retinogeniculate and geniculocortical connections. The amplified paired spike enhancement from retina to cortex ensures that signal transmission from retina to cortex is particularly effective when the retina fires a series of closely spaced action potentials.}, Author = {Kara, Prakash and Reid, R. Clay}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Visual Cortex;Photic Stimulation;research support, u.s. gov't, p.h.s. ;Visual Pathways;24 Pubmed search results 2008;21 Neurophysiology;Cats;Action Potentials;Geniculate Bodies;Electrophysiology;Reaction Time;Animals;Retinal Ganglion Cells;Synaptic Transmission;Visual Fields;Signal Processing, Computer-Assisted}, Month = {9}, Nlm_Id = {8102140}, Number = {24}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. pkara\@hms.harvard.edu}, Pages = {8547-57}, Pii = {23/24/8547}, Pubmed = {13679424}, Title = {Efficacy of retinal spikes in driving cortical responses}, Uuid = {3605C566-4980-49B7-AEF2-31C0C046D1B2}, Volume = {23}, Year = {2003}, url = {papers/Kara_JNeurosci2003.pdf}} @article{Karishma:2002, Abstract = {Treating adult male rats with subcutaneous pellets of dehydroepiandrosterone (DHEA) increased the number of newly formed cells in the dentate gyrus of the hippocampus, and also antagonized the suppressive of corticosterone (40 mg/kg body weight daily for 5 days). Neither pregnenolone (40 mg/kg/day), a precursor of DHEA, nor androstenediol (40 mg/kg/day), a major metabolite, replicated the effect of DHEA (40 mg/kg/day). Corticosterone reduced the number of cells labelled with a marker for neurons (NeuN) following a 28-day survival period, and this was also prevented by DHEA. DHEA by itself increased the number of newly formed neurons, but only if treatment was continued throughout the period of survival. Subcutaneous DHEA pellets stimulated neurogenesis in a small number of older rats ( approximately 12 months old). These results show that DHEA, a steroid prominent in the blood and cerebral environment of humans, but which decreases markedly with age and during major depressive disorder, regulates neurogenesis in the hippocampus and modulates the inhibitory effect of increased corticoids on both the formation of new neurons and their survival. 0953-816x Journal Article}, Author = {Karishma, K. K. and Herbert, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Eur J Neurosci}, Keywords = {Dentate Gyrus/cytology/*drug effects/*growth &development;Drug Administration Schedule;Animals;Corticosterone/blood/*pharmacology;Drug Interactions/physiology;Rats;Neuroprotective Agents/metabolism/pharmacology;C abstr;Rats, Inbred Strains;Male;Neurons/cytology/*drug effects/metabolism;Support, Non-U.S. Gov't;Cell Division/drug effects/*physiology;Cell Death/drug effects/physiology;Cell Differentiation/drug effects/physiology;04 Adult neurogenesis factors;Age Factors;Stem Cells/cytology/drug effects/metabolism;Cell Survival/drug effects/*physiology;Dehydroepiandrosterone/metabolism/*pharmacology;Immunohistochemistry;Androstenediol/pharmacology;Depression, Involutional/metabolism/pathology/physiopathology;Pregnenolone/pharmacology}, Number = {3}, Organization = {Department of Anatomy, University of Cambridge, Cambridge, CB2 3DY, UK.}, Pages = {445-53}, Pubmed = {12193187}, Title = {Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression}, Uuid = {29F93216-DF0C-463E-A85B-A85B114995ED}, Volume = {16}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12193187}} @article{Karl:2005, Abstract = {The doublecortin (DCX) gene encodes a 40-kDa microtubule-associated protein specifically expressed in neuronal precursors of the developing and adult CNS. Due to its specific expression pattern, attention was drawn to DCX as a marker for neuronal precursors and neurogenesis, thereby underscoring the importance of its promoter identification and promoter analysis. Here, we analysed the human DCX regulatory sequence and confined it to a 3.5-kb fragment upstream of the ATG start codon. We demonstrate by transient transfection experiments that this fragment is sufficient and specific to drive expression of reporter genes in embryonic and adult neuronal precursors. The activity of this regulatory fragment overlapped with the expression of endogenous DCX and with the young neuronal markers class III beta-tubulin isotype and microtubule-associated protein Map2ab but not with glial or oligodendroglial markers. Electrophysiological data further confirmed the immature neuronal nature of these cells. Deletions within the 3.5-kb region demonstrated the relevance of specific regions containing transcription factor-binding sites. Moreover, application of neurogenesis-related growth factors in the neuronal precursor cultures suggested the lack of direct signalling of these factors on the DCX promoter construct.}, Author = {Karl, Claudia and Couillard-Despres, Sebastien and Prang, Peter and Munding, Matthias and Kilb, Werner and Brigadski, Tanja and Pl{\"o}tz, Sonja and Mages, Wolfgang and Luhmann, Heiko and Winkler, J{\"u}rgen and Bogdahn, Ulrich and Aigner, Ludwig}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {02 Adult neurogenesis migration}, Month = {1}, Nlm_Id = {2985190R}, Number = {2}, Organization = {Volkswagen-Foundation-Research Group, University of Regensburg, Regensburg, Germany.}, Pages = {264-82}, Pii = {JNC2879}, Pubmed = {15663475}, Title = {Neuronal precursor-specific activity of a human doublecortin regulatory sequence}, Uuid = {52FAB77B-3251-4265-96E5-AA815626A9DF}, Volume = {92}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1471-4159.2004.02879.x}} @article{Karpova:2005, Abstract = {Inducible and reversible silencing of selected neurons in vivo is critical to understanding the structure and dynamics of brain circuits. We have developed Molecules for Inactivation of Synaptic Transmission (MISTs) that can be genetically targeted to allow the reversible inactivation of neurotransmitter release. MISTs consist of modified presynaptic proteins that interfere with the synaptic vesicle cycle when crosslinked by small molecule "dimerizers." MISTs based on the vesicle proteins VAMP2/Synaptobrevin and Synaptophysin induced rapid ( approximately 10 min) and reversible block of synaptic transmission in cultured neurons and brain slices. In transgenic mice expressing MISTs selectively in Purkinje neurons, administration of dimerizer reduced learning and performance of the rotarod behavior. MISTs allow for specific, inducible, and reversible lesions in neuronal circuits and may provide treatment of disorders associated with neuronal hyperactivity.}, Author = {Karpova, Alla Y. and Tervo, Dougal G. R. and Gray, Noah W. and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Vesicle-Associated Membrane Protein 2;research support, n.i.h., extramural ;Purkinje Cells;Gene Targeting;Animals;Cells, Cultured;Motor Activity;Synaptic Transmission;Synaptic Vesicles;Neurotransmitter Agents;in vitro ;Cross-Linking Reagents;Mice, Transgenic;Synaptophysin;Time Factors;research support, non-u.s. gov't ;Dimerization;Learning;21 Neurophysiology;Neurons;Mice;24 Pubmed search results 2008;Neural Inhibition}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {Howard Hughes Medical Institute, USA.}, Pages = {727-35}, Pii = {S0896-6273(05)00963-3}, Pubmed = {16337911}, Title = {Rapid and reversible chemical inactivation of synaptic transmission in genetically targeted neurons}, Uuid = {D46946D4-973F-4BC7-B20D-521F8F43044A}, Volume = {48}, Year = {2005}, url = {papers/Karpova_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.11.015}} @article{Karten:1997, Abstract = {97250444 0027-8424 Comment Journal Article}, Author = {Karten, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Embryo and Fetal Development/genetics;Gene Expression Regulation, Developmental;10 Development;Cerebral Cortex/*embryology;Genes, Homeobox;Animal;F;Support, U.S. Gov't, P.H.S.;Mammals/embryology;*Evolution}, Number = {7}, Organization = {Department of Neurosciences, University of California at San Diego, La Jolla 92093-0608, USA.}, Pages = {2800-4}, Pubmed = {9096300}, Title = {Evolutionary developmental biology meets the brain: the origins of mammalian cortex}, Uuid = {AD8012FE-D353-4E70-A611-F4C98376EE44}, Volume = {94}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9096300}} @article{Kashiwakura:2003, Abstract = {BACKGROUND: Bone marrow stromal cells (BMSCs) have many characteristics of mesenchymal stem cells that can differentiate into smooth muscle cells (SMCs). However, there have been few studies closely following the cell development of smooth muscle lineage among BMSCs. METHODS AND RESULTS: To investigate the possible existence of a cell population committed to the SMC lineage among bone marrow adhesion cells, we tried to detect and follow the in vitro differentiation of such a cell type by using a promoter-sorting method with a human SM22alpha promoter (-480 bp)/green fluorescent protein (GFP) construct. The construct was transfected to adhesion cells that appeared 5 days after the seeding of mononuclear cells from bone marrow. GFP was first detectable 5 days after the transfection in a cell population [Ad(G) cells], which expressed PDGF-beta but neither mature (calponin) nor immature (SMemb) SMC-specific proteins at that time. However, the cells were eventually grown into individual clones that expressed SMC-specific proteins (alpha-smooth muscle actin, calponin, and SM-1), suggesting that Ad(G) cells have partly at least progenitor properties. Because early studies have reported that PDGF-beta signaling plays pivotal roles in the differentiation of mesenchymal smooth muscle progenitor cells, Ad(G) cells might be putative mesenchymal smooth muscle progenitors expressing PDGF-beta. CONCLUSIONS: We demonstrated the presence of a cell population fated to become SMCs and followed their differentiation into SMCs among BMSCs.}, Author = {Kashiwakura, Yuji and Katoh, Youichi and Tamayose, Kenji and Konishi, Hakuoh and Takaya, Norihide and Yuhara, Senji and Yamada, Masanori and Sugimoto, Koichi and Daida, Hiroyuki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1524-4539}, Journal = {Circulation}, Keywords = {Stromal Cells;Cell Differentiation;Animals;Humans;Cells, Cultured;Muscle Proteins;Transfection;Microfilament Proteins;Mice, Inbred C57BL;Recombinant Fusion Proteins;11 Glia;Green Fluorescent Proteins;Antibodies;RNA, Messenger;Bone Marrow Cells;Cell Lineage;Calcium-Binding Proteins;Smooth Muscle Myosins;Promoter Regions (Genetics);Muscle, Smooth, Vascular;Mice;Stem Cells;Clone Cells;Receptor, Platelet-Derived Growth Factor beta;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22604924}, Month = {4}, Nlm_Id = {0147763}, Number = {16}, Organization = {Department of Cardiology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.}, Pages = {2078-81}, Pii = {01.CIR.0000070082.64414.B5}, Pubmed = {12707231}, Title = {Isolation of bone marrow stromal cell-derived smooth muscle cells by a human SM22alpha promoter: in vitro differentiation of putative smooth muscle progenitor cells of bone marrow}, Uuid = {23D30BBE-0BC1-4C19-A5D1-0D234D1A26B8}, Volume = {107}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.CIR.0000070082.64414.B5}} @article{Kasowski:1999, Abstract = {Olfactory receptor cell (ORC) axons terminate in the olfactory bulb glomerular neuropil, where they synapse with dendrites of mitral, tufted, and periglomerular neurons. We investigated the organization of the glomerular neuropil by using antibodies to both single- and double- label constituents for analyses with confocal microscopy. Electron microscopy (EM) was employed to assess the distribution of synaptic appositions within the glomerulus. Adult Sprague-Dawley rats were processed for immunocytochemistry with olfactory marker protein (OMP), synaptophysin, synapsin 1, glial fibrillary acidic protein (GFAP), and/or microtubule-associated protein 2 (MAP2). Equivalent rats were processed for transmission EM. Double labeling for OMP and MAP2 revealed two distinctive subcompartments within glomeruli: an axonal compartment containing predominately primary afferent axons with individual dendritic inserts and a complementary dendritic compartment that excluded primary afferent axons. Areas not occupied by OMP or MAP2 immunoreactivity were either immunoreactive for GFAP, indicating a glial process, or were blood vessels. Synaptophysin and synapsin 1 also showed differential labeling within the glomerulus. Synaptophysin strongly colocalized with OMP, whereas synapsin 1 was associated most strongly with MAP2. Reconstructions of glomeruli from EM montages revealed interdigitating axonal and dendritic subcompartments. The axonal subcompartments were composed primarily of ORC processes with individual or small groups of dendrites interspersed. Dendritic subcompartments were composed predominately of dendritic processes. Primary afferent axodendritic and local-circuit dendrodendritic synapses segregated within the glomerulus into the axonal and dendritic subcompartments, respectively. The results support the hypothesis of subcompartmental organization within olfactory bulb glomeruli.}, Author = {Kasowski, H. J. and Kim, H. and Greer, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Comp Neurol}, Keywords = {Synapsins/analysis;13 Olfactory bulb anatomy;I;Rats;Neurons/*ultrastructure;Microscopy, Confocal;Microtubule-Associated Proteins/analysis;Axons/ultrastructure;Animal;Rats, Sprague-Dawley;Glial Fibrillary Acidic Protein/analysis;Nerve Tissue Proteins/analysis;Synaptophysin/analysis;Synapses/ultrastructure;Olfactory Bulb/*ultrastructure;Support, U.S. Gov't, P.H.S.;Olfactory Receptor Neurons/ultrastructure;Microscopy, Electron;Biological Markers;Models, Neurological;Dendrites/ultrastructure}, Number = {2}, Organization = {Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.}, Pages = {261-74.}, Title = {Compartmental organization of the olfactory bulb glomerulus}, Uuid = {0A8A805C-BA19-4ACE-908E-A2A77A037E7B}, Volume = {407}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10213094}} @article{Kasthuri:2003, Abstract = {In developing mammalian muscle, axon branches of several motor neurons co-innervate the same muscle fibre. Competition among them results in the strengthening of one and the withdrawal of the rest. It is not known why one particular axon branch survives or why some competitions resolve sooner than others. Here we show that the fate of axonal branches is strictly related to the identity of the axons with which they compete. When two neurons co-innervate multiple target cells, the losing axon branches in each contest belong to the same neuron and are at nearly the same stage of withdrawal. The axonal arbor of one neuron engages in multiple sets of competitions simultaneously. Each set proceeds at a different rate and heads towards a common outcome based on the identity of the competitor. Competitive vigour at each of these sets of local competitions depends on a globally distributed resource: neurons with larger arborizations are at a competitive disadvantage when confronting neurons with smaller arborizations. An accompanying paper tests the idea that the amount of neurotransmitter released is this global resource.}, Author = {Kasthuri, Narayanan and Lichtman, Jeff W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Synapses;24 Pubmed search results 2008;10 Development;research support, non-u.s. gov't;21 Neurophysiology;10 circuit formation;Mice, Transgenic;research support, u.s. gov't, p.h.s.;Animals;Mice;Muscle, Skeletal;Neurons;Axons}, Month = {7}, Nlm_Id = {0410462}, Number = {6947}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St Louis, Missouri 63110, USA.}, Pages = {426-30}, Pii = {nature01836}, Pubmed = {12879070}, Title = {The role of neuronal identity in synaptic competition}, Uuid = {77E4C70B-FD49-495B-B696-03E42212685A}, Volume = {424}, Year = {2003}, url = {papers/Kasthuri_Nature2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature01836}} @article{Katagiri:2007, Abstract = {Local GABAergic circuits trigger visual cortical plasticity in early postnatal life. How these diverse connections contribute to critical period onset was investigated by nonstationary fluctuation analysis following laser photo-uncaging of GABA onto discrete sites upon individual pyramidal cells in slices of mouse visual cortex. The GABA(A) receptor number decreased on the soma-proximal dendrite (SPD), but not at the axon initial segment, with age and sensory deprivation. Benzodiazepine sensitivity was also higher on the immature SPD. Too many or too few SPD receptors in immature or dark-reared mice, respectively, were adjusted to critical period levels by benzodiazepine treatment in vivo, which engages ocular dominance plasticity in these animal models. Combining GAD65 deletion with dark rearing from birth confirmed that an intermediate number of SPD receptors enable plasticity. Site-specific optimization of perisomatic GABA response may thus trigger experience-dependent development in visual cortex.}, Author = {Katagiri, Hiroyuki and Fagiolini, Michela and Hensch, Takao K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Benzodiazepines;GABA Agonists;gamma-Aminobutyric Acid;Electric Stimulation;Animals;Patch-Clamp Techniques;Pyramidal Cells;Mice, Inbred C57BL;research support, non-u.s. gov't;Critical Period (Psychology);Dendrites;Pyridines;Animals, Newborn;Glutamate Decarboxylase;21 Neurophysiology;Mice, Knockout;Membrane Potentials;Age Factors;21 Activity-development;Mice;24 Pubmed search results 2008;Isoenzymes;Visual Cortex;Dominance, Ocular;Neural Inhibition;in vitro}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Laboratory for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.}, Pages = {805-12}, Pii = {S0896-6273(07)00146-8}, Pubmed = {17359916}, Title = {Optimization of somatic inhibition at critical period onset in mouse visual cortex}, Uuid = {244216C8-D92E-4FC7-84DC-0454C6E84A8A}, Volume = {53}, Year = {2007}, url = {papers/Katagiri_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.02.026}} @article{Kataoka:2003, Abstract = {Results of recent studies have indicated that bone marrow cells can differentiate into various cells of ectodermal, mesodermal, and endodermal origins when transplanted into the body. However, the problems associated with those experiments such as the long latent period, rareness of the event, and difficulty in controlling the processes have hampered detailed mechanistic studies. In the present study, we examined the potency of mouse bone marrow cells to differentiate into cells comprising skin tissues using a skin reconstitution assay. Bone marrow cells from adult green fluorescent protein (GFP)-transgenic mice were transplanted in a mixture of embryonic mouse skin cells (17.5 days post-coitus) onto skin defects made on the backs of nude mice. Within 3 weeks, fully differentiated skin with hair was reconstituted. GFP-positive cells were found in the epidermis, hair follicles, sebaceous glands, and dermis. The localization and morphology of the cells, results of immunohistochemistry, and results of specific staining confirmed that the bone marrow cells had differentiated into epidermal keratinocytes, sebaceous gland cells, follicular epithelial cells, dendritic cells, and endothelial cells under the present conditions. These results indicate that this system is suitable for molecular and cellular mechanistic studies on differentiation of stem cells to various epidermal and dermal cells.}, Author = {Kataoka, Ken and Medina, Reinhold J. and Kageyama, Tomofumi and Miyazaki, Masahiro and Yoshino, Tadashi and Makino, Teruhiko and Huh, Nam-Ho H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Cell Differentiation;Wound Healing;Animals;Bone Marrow Transplantation;Indicators and Reagents;Hair Follicle;Mice, Transgenic;Wounds, Penetrating;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Embryo;Mice, Nude;Mice, Inbred ICR;Bone Marrow Cells;Skin;Mice;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22870326}, Month = {10}, Nlm_Id = {0370502}, Number = {4}, Organization = {Department of Cell Biology, Okayama University Graduate School of Medicine and Dentistry, Shikatachou, Okayama, Japan.}, Pages = {1227-31}, Pubmed = {14507632}, Title = {Participation of adult mouse bone marrow cells in reconstitution of skin}, Uuid = {D8DB25EE-40B6-4DB0-86E1-A2BB77A7D3FC}, Volume = {163}, Year = {2003}} @article{Katayama:2006, Abstract = {Hematopoietic stem and progenitor cells (HSPC), attracted by the chemokine CXCL12, reside in specific niches in the bone marrow (BM). HSPC migration out of the BM is a critical process that underlies modern clinical stem cell transplantation. Here we demonstrate that enforced HSPC egress from BM niches depends critically on the nervous system. UDP-galactose ceramide galactosyltransferase-deficient (Cgt(-/-)) mice exhibit aberrant nerve conduction and display virtually no HSPC egress from BM following granulocyte colony-stimulating factor (G-CSF) or fucoidan administration. Adrenergic tone, osteoblast function, and bone CXCL12 are dysregulated in Cgt(-/-) mice. Pharmacological or genetic ablation of adrenergic neurotransmission indicates that norepinephrine (NE) signaling controls G-CSF-induced osteoblast suppression, bone CXCL12 downregulation, and HSPC mobilization. Further, administration of a beta(2) adrenergic agonist enhances mobilization in both control and NE-deficient mice. Thus, these results indicate that the sympathetic nervous system regulates the attraction of stem cells to their niche.}, Author = {Katayama, Yoshio and Battista, Michela and Kao, Wei-Ming M. and Hidalgo, Andr{\'e}s and Peired, Anna J. and Thomas, Steven A. and Frenette, Paul S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {11 Glia;22 Stem cells;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0413066}, Number = {2}, Organization = {Department of Medicine, Immunobiology Center and Black Family Stem Cell Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.}, Pages = {407-21}, Pii = {S0092-8674(05)01328-0}, Pubmed = {16439213}, Title = {Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow}, Uuid = {C6B15F81-4AEE-49E1-930B-8B0967BCFBAF}, Volume = {124}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.10.041}} @article{Katchanov:2001, Abstract = {After mild ischemic insults, many neurons undergo delayed neuronal death. Aberrant activation of the cell cycle machinery is thought to contribute to apoptosis in various conditions including ischemia. We demonstrate that loss of endogenous cyclin-dependent kinase (Cdk) inhibitor p16(INK4a) is an early and reliable indicator of delayed neuronal death in striatal neurons after mild cerebral ischemia in vivo. Loss of p27(Kip1), another Cdk inhibitor, precedes cell death in neocortical neurons subjected to oxygen-glucose deprivation in vitro. The loss of Cdk inhibitors is followed by upregulation of cyclin D1, activation of Cdk2, and subsequent cytoskeletal disintegration. Most neurons undergo cell death before entering S-phase, albeit a small number ( approximately 1\%) do progress to the S-phase before their death. Treatment with Cdk inhibitors significantly reduces cell death in vitro. These results show that alteration of cell cycle regulatory mechanisms is a prelude to delayed neuronal death in focal cerebral ischemia and that pharmacological interventions aimed at neuroprotection may be usefully directed at cell cycle regulatory mechanisms. 1529-2401 Journal Article}, Author = {Katchanov, J. and Harms, C. and Gertz, K. and Hauck, L. and Waeber, C. and Hirt, L. and Priller, J. and von Harsdorf, R. and Bruck, W. and Hortnagl, H. and Dirnagl, U. and Bhide, P. G. and Endres, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci}, Keywords = {Cyclin-Dependent Kinases/*antagonists &inhibitors/metabolism;Cell Hypoxia;Brain Ischemia/*metabolism/pathology;EE pdf;Disease Models, Animal;*Tumor Suppressor Proteins;Cyclin D1/metabolism;Animals;Cells, Cultured;In Situ Nick-End Labeling;Cell Cycle/physiology;Protein p16/deficiency/*metabolism;Mice, Inbred Strains;*Cell Cycle Proteins;Protein-Serine-Threonine Kinases/metabolism;Bromodeoxyuridine;08 Aberrant cell cycle;Support, U.S. Gov't, P.H.S.;Enzyme Inhibitors/pharmacology;Cell Death;Rats;*CDC2-CDC28 Kinases;Microtubule-Associated Proteins/deficiency/*metabolism;Purines/pharmacology;Support, Non-U.S. Gov't;Mice;Rats, Wistar;Oxygen/metabolism;Neurons/*metabolism/pathology;Glucose/deficiency/metabolism}, Number = {14}, Organization = {Experimental Neurology, Department of Neurology, Institute of Pharmacology and Toxicology, Charite, Humboldt-University of Berlin, D-10098 Berlin, Germany.}, Pages = {5045-53}, Pubmed = {11438580}, Title = {Mild cerebral ischemia induces loss of cyclin-dependent kinase inhibitors and activation of cell cycle machinery before delayed neuronal cell death}, Uuid = {3252827C-D395-11D9-A0E9-000D9346EC2A}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11438580}} @article{Kato:2000, Abstract = {It is well established that olfactory receptor cells are replaced during life. Periglomerular (PG) cells of the olfactory bulb have recently been demonstrated to be produced following proliferation and migration of periventricular neuronal precursor cells even in adulthood. The purpose of the present study was to examine the fate of newly formed PG cells in adult rodents. Using 5-bromodeoxyuridine (BrdU), we carried out a quantitative immunohistochemical analysis of BrdU-positive cells in the bulbar glomerular layer at different survival periods. Each number of BrdU-positive PG cells per 100 olfactory glomeruli was 34.1 +/- 3.3 (1 week), 57.2 +/- 2.7 (2 weeks), 28.0 +/- 4.7 (4 weeks) and 25.9 +/- 1.6 (8 weeks). These results indicate that bulbar PG cells, similar to olfactory receptor cells, are mostly replaced during life, and that the olfactory system is composed of disposable neuronal networks centrally as well as peripherally.}, Author = {Kato, T. and Yokouchi, K. and Kawagishi, K. and Fukushima, N. and Miwa, T. and Moriizumi, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Acta Otolaryngol}, Keywords = {I;13 Olfactory bulb anatomy}, Number = {7}, Organization = {Department of Anatomy, School of Medicine, Shinshu University, Matsumoto, Japan.}, Pages = {876-9.}, Title = {Fate of newly formed periglomerular cells in the olfactory bulb}, Uuid = {D7D9EBB8-18E0-486B-89B5-C49FD62F966A}, Volume = {120}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11132724}} @article{Kato:2001, Abstract = {It has been known that stem cells do exist in the central nervous system, and adult neurogenesis is continually taking place in the olfactory bulb during life. We report here, with the combined method of autoradiography using (3)H-thymidine and immunohistochemistry for a neuronal marker, that 65.3-76.9\%of calretinin-immunoreactive bulbar neurons are replaced during the short period of 6 weeks in the adult rodent. The results indicate that neuronal replacement is a common phenomenon in the olfactory bulb during life.}, Author = {Kato, T. and Yokouchi, K. and Fukushima, N. and Kawagishi, K. and Li, Z. and Moriizumi, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Neurosci Lett}, Keywords = {I;13 Olfactory bulb anatomy}, Number = {1}, Organization = {Department of Anatomy, Shinshu University School of Medicine, 390-8621, Matsumoto, Japan}, Pages = {17-20.}, Title = {Continual replacement of newly-generated olfactory neurons in adult rats}, Uuid = {EECDB633-E5B8-4C9E-B61F-1187913D0B0A}, Volume = {307}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11516564}} @article{Katou:2003, Abstract = {The checkpoint regulatory mechanism has an important role in maintaining the integrity of the genome. This is particularly important in S phase of the cell cycle, when genomic DNA is most susceptible to various environmental hazards. When chemical agents damage DNA, activation of checkpoint signalling pathways results in a temporary cessation of DNA replication. A replication-pausing complex is believed to be created at the arrested forks to activate further checkpoint cascades, leading to repair of the damaged DNA. Thus, checkpoint factors are thought to act not only to arrest replication but also to maintain a stable replication complex at replication forks. However, the molecular mechanism coupling checkpoint regulation and replication arrest is unknown. Here we demonstrate that the checkpoint regulatory proteins Tof1 and Mrc1 interact directly with the DNA replication machinery in Saccharomyces cerevisiae. When hydroxyurea blocks chromosomal replication, this assembly forms a stable pausing structure that serves to anchor subsequent DNA repair events. 1476-4687 Journal Article}, Author = {Katou, Y. and Kanoh, Y. and Bando, M. and Noguchi, H. and Tanaka, H. and Ashikari, T. and Sugimoto, K. and Shirahige, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Nature}, Keywords = {Mutation;Carrier Proteins/metabolism;*DNA Replication/drug effects/genetics;Saccharomyces cerevisiae/*cytology/drug effects/genetics/*metabolism;Hydroxyurea/pharmacology;*S Phase/drug effects;Chromosomes, Fungal/drug effects/*metabolism;Oligonucleotide Array Sequence Analysis;Bromodeoxyuridine/metabolism;08 Aberrant cell cycle;Protein Binding/drug effects;Nuclear Proteins/metabolism;Saccharomyces cerevisiae Proteins/genetics/*metabolism;Support, Non-U.S. Gov't;Macromolecular Systems;Cell Cycle Proteins/genetics/*metabolism;EE}, Number = {6952}, Organization = {Genome Structure and Function Team, Human Genome Research Group, RIKEN Genomic Science Center, 1-7-22 Suehiro-cho, Japan.}, Pages = {1078-83}, Pubmed = {12944972}, Title = {S-phase checkpoint proteins Tof1 and Mrc1 form a stable replication-pausing complex}, Uuid = {6C9875CF-9A4B-4ABF-A9BF-C0AA460DD90D}, Volume = {424}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12944972}} @article{Katz:2002, Abstract = {It has been generally believed that oncoretroviruses are dependent on mitosis for efficient nuclear entry of viral DNA. We previously identified a nuclear localization signal in the integrase protein of an oncoretrovirus, avian sarcoma virus (ASV), suggesting an active import mechanism for the integrase-DNA complex (G. Kukolj, R. A. Katz, and A. M. Skalka, Gene 223:157-163, 1998). Here, we have evaluated the requirement for mitosis in nuclear import and integration of ASV DNA. Using a modified ASV encoding a murine leukemia virus amphotropic env gene and a green fluorescent protein (GFP) reporter gene, DNA nuclear import was measured in cell cycle-arrested avian (DF-1) as well as human (HeLa) and mouse cells. The results showed efficient accumulation of nuclear forms of ASV DNA in gamma-irradiation-arrested cells. Efficient transduction of a GFP reporter gene was also observed after infection of cells that were arrested with gamma-irradiation, mitomycin C, nocodazole, or aphidicolin, confirming that nuclear import and integration of ASV DNA can occur in the absence of mitosis. By monitoring GFP expression in individual cells, we also obtained evidence for nuclear import of viral DNA during interphase in cycling cells. Lastly, we observed that ASV can transduce postmitotic mouse neurons. These results support an active nuclear import mechanism for the oncoretrovirus ASV and suggest that this mechanism can operate in both nondividing and dividing cells. 0022-538x Journal Article}, Author = {Katz, R. A. and Greger, J. G. and Darby, K. and Boimel, P. and Rall, G. F. and Skalka, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Virol}, Keywords = {Mitomycin/pharmacology;Human;Interphase;Animals;*Transduction, Genetic;Hydroxyurea/pharmacology;Nocodazole/pharmacology;Mitosis;Genetic Vectors/*genetics;15 Retrovirus mechanism;J pdf;Aphidicolin/pharmacology;DNA, Viral/metabolism;Mice, Inbred C57BL;G2 Phase;Hela Cells;Cell Line;Support, Non-U.S. Gov't;Chick Embryo;Sarcoma Viruses, Avian/*genetics;Research Design;Neurons;Active Transport, Cell Nucleus;Support, U.S. Gov't, P.H.S.;Mice;Genes, Reporter;Cell Nucleus/metabolism;Luminescent Proteins/genetics}, Number = {11}, Organization = {Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. R\_Katz\@fccc.edu}, Pages = {5422-34}, Pubmed = {11991971}, Title = {Transduction of interphase cells by avian sarcoma virus}, Uuid = {AE49FE62-0E3E-4764-BBE4-7616314163CA}, Volume = {76}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11991971}} @article{Katz:1996, Abstract = {Vision is critical for the functional and structural maturation of connections in the mammalian visual system. Visual experience, however, is a subset of a more general requirement for neural activity in transforming immature circuits into the organized connections that subserve adult brain function. Early in development, internally generated spontaneous activity sculpts circuits on the basis of the brain's "best guess" at the initial configuration of connections necessary for function and survival. With maturation of the sense organs, the developing brain relies less on spontaneous activity and increasingly on sensory experience. The sequential combination of spontaneously generated and experience-dependent neural activity endows the brain with an ongoing ability to accommodate to dynamically changing inputs during development and throughout life.}, Author = {Katz, L. C. and Shatz, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-03-13 12:11:28 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Animals;Synapses;Neuronal Plasticity;review;Visual Pathways;Axons;Nerve Growth Factors;Vision;Action Potentials;21 Neurophysiology;21 Activity-development;Visual Cortex;Geniculate Bodies;Retinal Ganglion Cells;visual system;Spontaneous activity;Synaptic Transmission;refinement;Neocortex;synapse formation;Competitive Behavior;experience dependent plasticity;}, Month = {11}, Nlm_Id = {0404511}, Number = {5290}, Organization = {Howard Hughes Medical Institute and the Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. larry\@neuro.duke.edu}, Pages = {1133-8}, Pubmed = {8895456}, Title = {Synaptic activity and the construction of cortical circuits}, Uuid = {EA60C1CD-4CF5-46E7-B86F-9627118B32FB}, Volume = {274}, Year = {1996}, url = {papers/Katz_Science1996.pdf}} @article{Kaufmann:1989, Abstract = {Previous studies showed that few foci of cerebro-cortical microdysgenesis (molecular layer neuronal ectopias and focal laminar dysplasia) are present in up to 26\%of variably processed normal brains; they are more common in the right inferior frontal region. Brains of male developmental dyslexics processed in serial histologic sections showed 30 to 140 foci of these types of anomalies, predominantly in left perisylvian cortex. Here, we present the results of a detailed analysis of ten normal brains also processed in serial sections. The ages ranged from 3.5 to 87 years, all male. Three brains showed abnormalities similar in type to those of the dyslexic, but in far smaller numbers and in different locations: two showed a single cingulate focus--one right, one left; the third brain showed two right supratemporal foci. We conclude that the present form of developmental anomaly is rare in normal brains, and that the findings in the dyslexic brains may be significant.}, Author = {Kaufmann, W. E. and Galaburda, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {10 Development;Child, Preschool;Humans;Middle Aged;Brain;Child;Reference Values;Dyslexia;research support, non-u.s. gov't;Brain Diseases;Warts;Aged;Brain Neoplasms;Male;10 genetics malformation;Aged, 80 and over;research support, u.s. gov't, p.h.s.;Cerebral Cortex;Adult;24 Pubmed search results 2008;Choristoma;Adolescent}, Month = {2}, Nlm_Id = {0401060}, Number = {2 Pt 1}, Organization = {Dyslexia Neuroanatomical Laboratory, Beth Israel Hospital, Boston, MA 02215.}, Pages = {238-44}, Pubmed = {2915796}, Title = {Cerebrocortical microdysgenesis in neurologically normal subjects: a histopathologic study}, Uuid = {D57F93A7-8BB8-4EBB-8527-E2D62EA6B849}, Volume = {39}, Year = {1989}} @article{Kaur:1997, Abstract = {The pineal gland of rats of various ages (1-21 days old) was examined by immunohistochemistry and electron microscopy. Numerous widely distributed cells identified as macrophages/microglia were immunoreactive with the monoclonal antibodies OX-42, OX-18, OX-6, and ED1, indicating that they expressed complement type 3 (CR3) receptors, major histocompatibility complex class I and II antigens, and antigens of monocyte/macrophage lineage as detected by the antibodies, respectively. Following an intraperitoneal injection of rhodamine isothiocyanate (RhIC) in all age groups, the cells emitted a bright fluorescence. They were also labeled by horseradish peroxidase (HRP), as demonstrated in both light and electron microscopy. An HRP reaction was observed in vesicles and lysosomes at the ultrastructural level. A remarkable feature was the uptake of these tracers by pinealocytes. In light microscopy, the pinealocytes showed a punctate reaction product 3-24 hours after HRP injection. By electron microscopy, the reaction product was observed in vesicles, lysosomes, and some rod-like structures in the cytoplasm. On the basis of their immunophenotypic features, it is suggested that the macrophages/microglia in the pineal gland are active phagocytes which are also probably involved in the immunoregulatory function in the gland. The avid uptake of RhIC and HRP from the circulation by these cells suggests that serum-derived substances that may gain access to the parenchyma of the gland are being constantly monitored. The labeling of pinealocytes with HRP suggests that the functional activities of these cells are being modulated by serum-derived substances.}, Author = {Kaur, C. and Wu, C. H. and Ling, E. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0742-3098}, Journal = {J Pineal Res}, Keywords = {Fluorescent Dyes;Rhodamines;Pineal Gland;Animals;Macrophages;Rats;Antigens, Differentiation;Female;Microglia;Rats, Wistar;Not relevant;11 Glia;Male;Support, Non-U.S. Gov't;Macrophage-1 Antigen;Antibodies, Monoclonal;Horseradish Peroxidase;Immunohistochemistry;Microscopy, Electron;Histocompatibility Antigens Class I;Histocompatibility Antigens Class II}, Medline = {97356831}, Month = {4}, Nlm_Id = {8504412}, Number = {3}, Organization = {Department of Anatomy, Faculty of Medicine, National University of Singapore, Kent Ridge, Singapore.}, Pages = {137-44}, Pubmed = {9213267}, Title = {Immunohistochemical and tracer studies of macrophages/microglia in the pineal gland of postnatal rats}, Uuid = {B79450A1-E7D9-49DD-978F-81CAB6CDC756}, Volume = {22}, Year = {1997}, url = {papers/Kaur_JPinealRes1997.pdf}} @article{Kaushal:2003, Abstract = {Frequent chromosomal aneuploidy has recently been discovered in normal neurons of the developing and mature murine CNS. Toward a more detailed understanding of aneuploidy and its effects on normal CNS cells, we examined the genomes of cells in the postnatal subventricular zone (SVZ), an area that harbors a large number of neural stem and progenitor cells (NPCs), which give rise to neurons and glia. Here we show that NPCs, neurons, and glia from the SVZ are frequently aneuploid. Karyotyping revealed that approximately 33\%of mitotic SVZ cells lost or gained chromosomes in vivo, whereas interphase fluorescence in situ hybridization demonstrated aneuploidy in postnatal-born cells in the olfactory bulb (OB) in vivo, along with neurons, glia, and NPCs in vitro. One possible consequence of aneuploidy is altered gene expression through loss of heterozygosity (LOH). This was examined in a model of LOH: loss of transgene expression in mice hemizygous for a ubiquitously expressed enhanced green fluorescent protein (eGFP) transgene on chromosome 15. Concurrent examination of eGFP expression, transgene abundance, and chromosome 15 copy number demonstrated that a preponderance of living SVZ and OB cells not expressing eGFP lost one copy of chromosome 15; the eGFP transgene was lost in these cells as well. Although gene expression profiling revealed changes in expression levels of several genes relative to GFP-expressing controls, cells with LOH at chromosome 15 were morphologically normal and proliferated or underwent apoptosis at rates similar to those of euploid cells in vitro. These findings support the view that NPCs and postnatal-born neurons and glia can be aneuploid in vivo and functional gene expression can be permanently altered in living neural cells by chromosomal aneuploidy. 1529-2401 Journal Article}, Author = {Kaushal, D. and Contos, J. J. and Treuner, K. and Yang, A. H. and Kingsbury, M. A. and Rehen, S. K. and McConnell, M. J. and Okabe, M. and Barlow, C. and Chun, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {J Neurosci}, Keywords = {Transgenes;In Situ Hybridization, Fluorescence;Animals;Brain/cytology/growth &development/*metabolism;*Gene Expression Regulation, Developmental;*Chromosomes;EE pdf;*Aneuploidy;Mice, Transgenic;08 Aberrant cell cycle;Cell Survival/genetics;Stem Cells/cytology/metabolism;Support, Non-U.S. Gov't;Cell Division/genetics;Karyotyping;Support, U.S. Gov't, P.H.S.;Loss of Heterozygosity;Mice;Neurons/cytology/metabolism;Lateral Ventricles/cytology/*metabolism;Luminescent Proteins/biosynthesis/genetics}, Number = {13}, Organization = {Neuroscience Program, Department of Pharmacology, University of California, San Diego, San Diego, California 92093, USA.}, Pages = {5599-606}, Title = {Alteration of gene expression by chromosome loss in the postnatal mouse brain}, Uuid = {F7A64D80-10B9-4A3C-909D-D04D0CF976CB}, Volume = {23}, Year = {2003}, url = {papers/Kaushal_JNeurosci2003.pdf}} @article{Kawaguchi:1993, Abstract = {1. To test the hypothesis that physiologically and morphologically different cortical nonpyramidal cells express different calcium-binding proteins, whole-cell current-clamp recording in vitro was combined with intracellular staining and double immunofluorescence in layer V of frontal cortex of rats 16-20 days old. 2. Nonpyramidal cells were first characterized as fast-spiking (FS) or low-threshold spike (LTS) cells, injected with biocytin, and subsequently stained immunohistochemically for parvalbumin and calbindinD28k. 3. FS cells were identified by input resistances <350 M omega, spike width at half amplitude <0.8 ms, and virtually no spike frequency adaptation of spike trains by depolarizing pulses. LTS cells were identified by input resistances >350 M omega, spike width at half amplitude >0.8 ms, and the discharge of low-threshold spikes from hyperpolarized potentials. Repetitive firing could be induced by a combination of stimulation-induced excitatory postsynaptic potentials with depolarization in FS cells. Repetitive firing was not observed in LTS cells under these conditions. 4. After biocytin injection of layer V cells characterized in this way, subsequent double immunostaining showed that all biocytin-labeled parvalbumin-immunoreactive cells (n = 18) belonged to the FS cells (FS-PV cells), whereas all biocytin-labeled calbindinD28k-immunoreactive cells (n = 10) belonged to the LTS cells (LTS-Calb cells). 5. FS-PV cells had smooth or sparsely spiny dendrites, whereas LTS-Calb cells had dendrites with a modest number of spines but fewer than pyramidal cells. FS-PV cells showed denser axonal branches near their somata and extended axons in a more horizontal direction. Some of them could be identified as basket cells by the presence of terminal boutons surrounding somata of other cells. LTS-Calb cells extended their main axons more vertically up to layer I. 6. Double immunofluorescent staining revealed that very few cells in layer V showed immunoreactivity for both calcium-binding proteins but that most cells immunoreactive for the calcium-binding proteins in layer V were also immunoreactive for gamma-aminobutyric acid. 7. These results suggest that GABAergic nonpyramidal cells in layer V of neocortex can be divided into two functional groups on the basis of different firing modes, axonal distributions, and calcium-binding protein immunoreactivity: 1) FS-PV cells show repetitive firing by synaptic activation, have axonal arborizations that are more dense near their somata and oriented horizontally, and the cells exhibit parvalbumin immunoreactivity and 2) LTS cells show low-threshold spikes, have more vertical axonal arborizations up to layer I, and exhibit calbindinD28K immunoreactivity. 0022-3077 Journal Article}, Author = {Kawaguchi, Y. and Kubota, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurophysiol}, Keywords = {18 Classic Neuroanatomy Physiology;Electric Stimulation;Calcium-Binding Protein, Vitamin D-Dependent/*metabolism;Frontal Lobe/*cytology;gamma-Aminobutyric Acid/physiology;Rats;Synaptic Transmission/*physiology;Parvalbumins/*metabolism;Rats, Wistar;M;Neurons/physiology;Fluorescent Antibody Technique;Animals;Support, Non-U.S. Gov't;Tissue Culture}, Number = {1}, Organization = {Laboratory for Neural Systems, Frontier Research Program, Institute of Physical and Chemical Research (RIKEN), Wako, Japan.}, Pages = {387-96}, Pubmed = {8395585}, Title = {Correlation of physiological subgroupings of nonpyramidal cells with parvalbumin- and calbindinD28k-immunoreactive neurons in layer V of rat frontal cortex}, Uuid = {41EE6803-ABFD-4C70-8480-A5C15FACB5A8}, Volume = {70}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8395585}} @article{Kawakami:1999, Abstract = {Green fluorescent protein (GFP) transgenic (GFP+) mice express GFP in most tissues except erythrocytes and hair. Immune responses of GFP+ mouse and their application to studies of lymphocyte development were investigated. Flow cytometric analyses revealed that differentiation patterns of lymphocytes from GFP+ mice are equivalent to those from parental C57BL/6 mice. There was no difference in mature T-cell proliferative ability in response to allogeneic stimulator cells or anti-CD3epsilon stimulation between GFP+ and C57BL/6 mice. Furthermore, the anti-OVA antibody response of GFP+ mice was also the same as that of C57BL/6 mice. Taken together, these results show no immunological differences between GFP+ and C57BL/6 mice. Bone marrow transplantation and in vitro thymus reconstitution experiments were performed in an attempt to apply the GFP+ mice to the analysis of lymphocyte development. When bone marrow cells from GFP+ mice were transplanted. T and B lymphocytes containing GFP developed normally in scid recipients. Next we examined intrathymic T-cell development by hanging drop culture methods. GFP+ and CD4+8+ immature T-cells developed normally from bone marrow cells in the reconstituted thymus. The experimental system using hematopoietic cells from GFP+ mice is a powerful tool for visualizing lymphocyte development.}, Author = {Kawakami, N. and Sakane, N. and Nishizawa, F. and Iwao, M. and Fukada, S. I. and Tsujikawa, K. and Kohama, Y. and Ikawa, M. and Okabe, M. and Yamamoto, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0165-2478}, Journal = {Immunol Lett}, Keywords = {Immune System;Bone Marrow;Luminescent Proteins;Receptors, Antigen, T-Cell;Research Support, Non-U.S. Gov't;Antigens, CD3;Mice, Inbred C57BL;Lymphocytes;Thymus Gland;11 Glia;Mice, Transgenic;Mice, SCID;Animals;Mice;Green Fluorescent Proteins;Spleen;Transplantation Chimera}, Medline = {20120462}, Month = {12}, Nlm_Id = {7910006}, Number = {3}, Organization = {Department of Immunology, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.}, Pages = {165-71}, Pii = {S0165247899001522}, Pubmed = {10656669}, Title = {Green fluorescent protein-transgenic mice: immune functions and their application to studies of lymphocyte development}, Uuid = {D0B5AA69-B750-4279-8E7F-E53498FC98B7}, Volume = {70}, Year = {1999}} @article{Kastner:1972, Author = {K{\"a}stner, I. and M{\"u}ller, M. and Rougerie, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0033-2739}, Journal = {Psychiatr Neurol Med Psychol (Leipz)}, Keywords = {Animals;Agar;Stereotaxic Techniques;Rats;Seizures;Comparative Study;Gelatin;Brain;21 Epilepsy;Epilepsy;Disease Models, Animal;Male;Olfactory Bulb;Potassium;Cerebral Cortex;21 Neurophysiology;Sodium;Polyethylenes;24 Pubmed search results 2008;Electroencephalography;Cobalt;Waxes}, Medline = {74030018}, Month = {10}, Nlm_Id = {0376467}, Number = {10}, Pages = {581-6}, Pubmed = {4584754}, Title = {[Comparative animal experimental studies on the production of chronic epileptiform focal activity]}, Uuid = {C57383B3-241E-49D9-AAF5-AF9244D517A4}, Volume = {24}, Year = {1972}} @article{Keays:2007, Abstract = {The development of the mammalian brain is dependent on extensive neuronal migration. Mutations in mice and humans that affect neuronal migration result in abnormal lamination of brain structures with associated behavioral deficits. Here, we report the identification of a hyperactive N-ethyl-N-nitrosourea (ENU)-induced mouse mutant with abnormalities in the laminar architecture of the hippocampus and cortex, accompanied by impaired neuronal migration. We show that the causative mutation lies in the guanosine triphosphate (GTP) binding pocket of alpha-1 tubulin (Tuba1) and affects tubulin heterodimer formation. Phenotypic similarity with existing mouse models of lissencephaly led us to screen a cohort of patients with developmental brain anomalies. We identified two patients with de novo mutations in TUBA3, the human homolog of Tuba1. This study demonstrates the utility of ENU mutagenesis in the mouse as a means to discover the basis of human neurodevelopmental disorders.}, Author = {Keays, David A. and Tian, Guoling and Poirier, Karine and Huang, Guo-Jen J. and Siebold, Christian and Cleak, James and Oliver, Peter L. and Fray, Martin and Harvey, Robert J. and Moln{\'a}r, Zolt{\'a}n and Pi\~{n}on, Maria C. and Dear, Neil and Valdar, William and Brown, Steve D. M. and Davies, Kay E. and Rawlins, J. Nicholas P. and Cowan, Nicholas J. and Nolan, Patrick and Chelly, Jamel and Flint, Jonathan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008;Memory Disorders;Male;Cerebral Cortex;10 Development;Animals;Serine;Dimerization;Hippocampus;Cell Movement;Phenotype;research support, n.i.h., extramural;DNA Mutational Analysis;Anxiety;Molecular Sequence Data;Mice, Mutant Strains;Tubulin;Behavior, Animal;21 Epilepsy;Chromosome Mapping;Mutation;Amino Acid Sequence;Guanosine Triphosphate;Glutamic Acid;Female;research support, non-u.s. gov't;21 Neurophysiology;Mice;Neurons;Humans}, Month = {1}, Nlm_Id = {0413066}, Number = {1}, Organization = {Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, OX3 7BN, UK.}, Pages = {45-57}, Pii = {S0092-8674(06)01611-4}, Pubmed = {17218254}, Title = {Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans}, Uuid = {A527F883-1A06-4BC0-8E22-212E34121B9E}, Volume = {128}, Year = {2007}, url = {papers/Keays_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.12.017}} @article{Kee:2001, Abstract = {The dentate gyrus is one of the few areas of the mammalian brain where new neurons are continuously produced in adulthood. Certain insults such as epileptic seizures and ischemia are known to enhance the rate of neuronal production. We analyzed this phenomenon using the temporary occlusion of the two carotid arteries combined with arterial hypotension as a method to induce ischemia in rats. We measured the rate of cell production and their state of differentiation with a mitotic indicator, bromodeoxyuridine (BrdU), in combination with the immunohistochemical detection of neuronal markers. One week after the ischemic episode, the cell production in dentate gyrus was increased two- to threefold more than the basal level seen in control animals. Two weeks after ischemia, over 60\%of these cells became young neurons as determined by colabeling with BrdU and a cytoplasmic protein (CRMP-4) involved in axonal guidance during development. Five weeks after the ischemia, over 60\%of new neurons expressed calbindin, a calcium-binding protein normally expressed in mature granule neurons. In addition to more cells being generated, a greater proportion of all new cells remained in the differentiated but not fully mature state during the 2- to 5-week period after ischemia. The maturation rate of neurons as determined by the calbindin labeling and by the rate of migration from a proliferative zone into the granule cell layer was not changed when examined 5 weeks after ischemia. The results support the hypothesis that survival of dentate gyrus after ischemia is linked with enhanced neurogenesis. Additional physiological stimulation after ischemia may be exploited to stimulate maturation of new neurons and to offer new therapeutic strategies for promoting recovery of neuronal circuitry in the injured brain. 0014-4819 Journal Article}, Author = {Kee, N. J. and Preston, E. and Wojtowicz, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Exp Brain Res}, Keywords = {Cerebrovascular Accident/pathology;Cytoplasm/chemistry;Ischemic Attack, Transient/*pathology;Rats, Sprague-Dawley;D abstr;Cell Division/physiology;Cell Survival/physiology;Rats;06 Adult neurogenesis injury induced;Neurons/chemistry/*cytology;Dentate Gyrus/*blood supply/*cytology;Cell Differentiation/physiology;Support, Non-U.S. Gov't;Animals;Bromodeoxyuridine;Antimetabolites;Calcium-Binding Protein, Vitamin D-Dependent/analysis}, Number = {3}, Organization = {Department of Physiology, University of Toronto, ON, Canada.}, Pages = {313-20}, Pubmed = {11243473}, Title = {Enhanced neurogenesis after transient global ischemia in the dentate gyrus of the rat}, Uuid = {2C5B9D0D-EC81-11DA-8605-000D9346EC2A}, Volume = {136}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11243473}} @article{Kee:2002, Abstract = {Adult animals continue to produce new neurons in the dentate gyrus of hippocampus. Until now, the principal method of studying neurogenesis has been to inject either tritiated thymidine or 5'-Bromo-2- deoxyuridine (BrdU) intraperitoneally followed by autoradiographic or immunohistochemical detection methods respectively. However, such exogenous markers may produce toxic effects. Our objective was to determine whether Ki-67, a nuclear protein expressed in all phases of the cell cycle except the resting phase, can be used as an alternative, endogenous marker. Using immunohistochemistry, we examined Ki-67 and BrdU expression pattern in rats. Ki-67 was expressed within the proliferative zone of the dentate gyrus and its expression pattern mimicked that of BrdU when examined soon after exogenous BrdU administration. Quantitative comparison of BrdU and Ki-67-positive cells showed 50\%higher numbers of the latter when examined 24 h after the BrdU injection. This was expected, since BrdU can be incorporated into DNA only during the S-phase of the mitotic process, whereas Ki-67 is expressed for its whole duration. Experimental increases (by ischemia) or reductions (by radiation) in the number of mitotic cells produced parallel changes in BrdU and Ki-67 signals. Thus, Ki-67 is an effective mitotic marker and has most of the benefits of BrdU and none of the costs. This study provides evidence for Ki-67 to be used as a marker of proliferation in the initial phase of adult neurogenesis.}, Author = {Kee, N. and Sivalingam, S. and Boonstra, R. and Wojtowicz, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci Methods}, Keywords = {01 Adult neurogenesis general;02 Adult neurogenesis migration;A, BB, T abstr}, Number = {1}, Organization = {Department of Physiology, Medical Sciences Building, University of Toronto, Ont., M5S 1A8, Toronto, Canada}, Pages = {97-105.}, Title = {The utility of Ki-67 and BrdU as proliferative markers of adult neurogenesis}, Uuid = {0BD40556-A31E-4A73-BBEB-FC28380929C3}, Volume = {115}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11897369}} @article{Keirstead:1999, Abstract = {Transplantation offers a means of identifying the differentiation and myelination potential of early neural precursors, features relevant to myelin regeneration in demyelinating diseases. In the postnatal rat brain, precursor cells expressing the polysialylated (PSA) form of the neural cell adhesion molecule NCAM have been shown to generate mostly oligodendrocytes and astrocytes in vitro (Ben-Hur et al., 1998). Immunoselected PSA-NCAM+ newborn rat CNS precursors were expanded as clusters with FGF2 and grafted into a focal demyelinating lesion in adult rat spinal cord. We show that these neural precursors can completely remyelinate such CNS lesions. While PSA-NCAM+ precursor clusters contain rare P75+ putative neural crest precursors, they do not generate Schwann cells in vitro even in the presence of glial growth factor. Yet they generate oligodendrocytes, astrocytes, and Schwann cells in vivo when confronted with demyelinated axons in a glia-free area. We confirmed the transplant origin of these Schwann cells using Y chromosome in situ hybridization and immunostaining for the peripheral myelin protein P0 of tissue from female rats that had been grafted with male cell clusters. The number and distribution of Schwann cells within remyelinated tissue, and the absence of P0 mRNAs in donor cells, indicated that Schwann cells were generated by expansion and differentiation of transplanted PSA-NCAM+ neural precursors and were not derived from contaminating Schwann cells. Thus, transplantation into demyelinated CNS tissue reveals an unexpected differentiation potential of a neural precursor, resulting in remyelination of CNS axons by PNS and CNS myelin-forming cells.}, Author = {Keirstead, H. S. and Ben-Hur, T. and Rogister, B. and O'Leary, M. T. and Dubois-Dalcq, M. and Blakemore, W. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Neural Cell Adhesion Molecules;Myelin P0 Protein;Cell Differentiation;Rats, Inbred Lew;Animals;Cells, Cultured;Coculture Techniques;Brain Tissue Transplantation;Rats;Nervous System;Brain;Oligodendroglia;Female;Axons;Nerve Fibers, Myelinated;Rats, Wistar;Male;Reverse Transcriptase Polymerase Chain Reaction;Nerve Regeneration;Schwann Cells;Animals, Newborn;Sialic Acids;Neural Cell Adhesion Molecule L1;24 Pubmed search results 2008;Y Chromosome;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {99389882}, Month = {9}, Nlm_Id = {8102140}, Number = {17}, Organization = {Medical Research Council Cambridge Centre for Brain Repair and Department of Clinical Veterinary Medicine, Cambridge, United Kingdom CB3 0ES.}, Pages = {7529-36}, Pubmed = {10460259}, Title = {Polysialylated neural cell adhesion molecule-positive CNS precursors generate both oligodendrocytes and Schwann cells to remyelinate the CNS after transplantation}, Uuid = {32D0DC09-EB33-453A-B67A-B242BB5897DC}, Volume = {19}, Year = {1999}} @article{Keller:1981, Author = {Keller, G. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Visual Cortex;Axonal Transport;Cats;Not relevant;11 Glia;Afferent Pathways;Horseradish Peroxidase;Support, Non-U.S. Gov't;Animals;Neurons;Corpus Callosum}, Medline = {81221426}, Nlm_Id = {7605074}, Number = {4}, Pages = {703-12}, Pubmed = {6165925}, Title = {Callosal connections of suprasylvian visual areas in the cat}, Uuid = {73C925B9-5B44-4FA6-9F4A-B0328DB54A5B}, Volume = {6}, Year = {1981}} @article{Keller-Peck:2001, Abstract = {In developing muscle, synapse elimination reduces the number of motor axons that innervate each postsynaptic cell. This loss of connections is thought to be a consequence of axon branch trimming. However, branch retraction has not been observed directly, and many questions remain, such as: do all motor axons retract branches, are eliminated branches withdrawn synchronously, and are withdrawing branches localized to particular regions? To address these questions, we used transgenic mice that express fluorescent proteins in small subsets of motor axons, providing a unique opportunity to reconstruct complete axonal arbors and identify all the postsynaptic targets. We found that, during early postnatal development, each motor axon loses terminal branches, but retracting branches withdraw asynchronously and without obvious spatial bias, suggesting that local interactions at each neuromuscular junction regulate synapse elimination.}, Author = {Keller-Peck, C. R. and Walsh, M. K. and Gan, W. B. and Feng, G. and Sanes, J. R. and Lichtman, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Animals;Bacterial Proteins;Synapses;Aging;research support, u.s. gov't, p.h.s. ;Axons;Mice, Transgenic;Green Fluorescent Proteins;research support, non-u.s. gov't ;Animals, Newborn;Neuromuscular Junction;21 Neurophysiology;Muscle, Skeletal;Motor Neurons;Mice;Luminescent Proteins;24 Pubmed search results 2008;Models, Neurological}, Month = {8}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.}, Pages = {381-94}, Pii = {S0896-6273(01)00383-X}, Pubmed = {11516396}, Title = {Asynchronous synapse elimination in neonatal motor units: studies using GFP transgenic mice}, Uuid = {B40D3D39-051C-4514-BE33-7C8414B71939}, Volume = {31}, Year = {2001}, url = {papers/Keller-Peck_Neuron2001.pdf}} @article{Kelly:2004, Abstract = {We characterize the survival, migration, and differentiation of human neurospheres derived from CNS stem cells transplanted into the ischemic cortex of rats 7 days after distal middle cerebral artery occlusion. Transplanted neurospheres survived robustly in naive and ischemic brains 4 wk posttransplant. Survival was influenced by proximity of the graft to the stroke lesion and was negatively correlated with the number of IB4-positive inflammatory cells. Targeted migration of the human cells was seen in ischemic animals, with many human cells migrating long distances ( approximately 1.2 mm) predominantly toward the lesion; in naive rats, cells migrated radially from the injection site in smaller number and over shorter distances (0.2 mm). The majority of migrating cells in ischemic rats had a neuronal phenotype. Migrating cells between the graft and the lesion expressed the neuroblast marker doublecortin, whereas human cells at the lesion border expressed the immature neuronal marker beta-tubulin, although a small percentage of cells at the lesion border also expressed glial fibrillary acid protein (GFAP). Thus, transplanted human CNS (hCNS)-derived neurospheres survived robustly in naive and ischemic brains, and the microenvironment influenced their migration and fate.}, Author = {Kelly, S. and Bliss, T. M. and Shah, A. K. and Sun, G. H. and Ma, M. and Foo, W. C. and Masel, J. and Yenari, M. A. and Weissman, I. L. and Uchida, N. and Palmer, T. and Steinberg, G. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Neurons;Cell Differentiation;Fetus;Brain Ischemia;17 Transplant Regeneration;Transplantation, Heterologous;Rats;Research Support, U.S. Gov't, P.H.S.;Biological Markers;Cell Survival;Arterial Occlusive Diseases;22 Stem cells;Humans;Cell Movement;Cerebral Cortex;Stem Cell Transplantation;Animals}, Month = {8}, Nlm_Id = {7505876}, Number = {32}, Organization = {Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA.}, Pages = {11839-44}, Pii = {0404474101}, Pubmed = {15280535}, Title = {Transplanted human fetal neural stem cells survive, migrate, and differentiate in ischemic rat cerebral cortex}, Uuid = {0C56BAC8-0911-4F68-B845-57E10EB5F937}, Volume = {101}, Year = {2004}, url = {papers/Kelly_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0404474101}} @article{Kempermann:1998, Abstract = {New neurons are continuously born in the dentate gyrus of the adult mouse hippocampus, and regulation of adult neurogenesis is influenced by both genetic and environmental determinants. Mice of the 129/SvJ strain have significantly less hippocampal neurogenesis than other inbred mouse strains [1] and do not perform well in learning tasks. Here, the impact of environmental stimuli on brain plasticity during adulthood of 129/SvJ mice was studied using 'enriched environments'where mice receive complex inanimate and social stimulation [2,3]. In contrast to our earlier reports on mice of the C57BL/6 strain - which are competent in learning tasks and in which environmental stimulation did not influence cell proliferation [4,5] - environmentally stimulated 129/SvJ mice were found to have twice as many proliferating cells in the dentate gyrus compared with mice in standard housing. Environmental stimulation fostered the survival of newborn cells in 129/SvJ mice; this effect had also been seen in C57BL/6 mice. Phenotypic analysis of the surviving cells revealed that environmental stimulation resulted in 67\%more new neurons. In combination with our earlier results, these data indicate a differential impact of inheritable traits on the environmental regulation of adult hippocampal neurogenesis. In addition, we observed behavioral changes in environmentally stimulated 129/SvJ mice.}, Author = {Kempermann, G. and Brandon, E. P. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Curr Biol}, Keywords = {Neurons/*cytology/*physiology;Dentate Gyrus/*cytology/*physiology;Species Specificity;*Neuronal Plasticity;Female;Comparative Study;Housing, Animal;Cell Division;*Social Environment;*Maze Learning;Animal;Mice, Inbred C57BL;Support, U.S. Gov't, P.H.S.;04 Adult neurogenesis factors;Mice;C abstr;Mice, Inbred Strains}, Number = {16}, Organization = {The Salk Institute for Biological Studies Laboratory of Genetics 10010 North Torrey Pines Road, La Jolla, California, 92037, USA.}, Pages = {939-42.}, Title = {Environmental stimulation of 129/SvJ mice causes increased cell proliferation and neurogenesis in the adult dentate gyrus}, Uuid = {258181F8-F7A5-4BCE-AE3E-9B3637EAC3CE}, Volume = {8}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9707406%20http://www.biomednet.com/article/bb8p55}} @article{Kempermann:2004, Abstract = {'Function' is the key criterion for determining whether adult neurogenesis - be it endogenous, induced, or after transplantation - is successful and has truly generated new nerve cells. Function, however, is an elusive and problematic term. A satisfying statement of function will require evaluation on the three conceptual levels of cells, networks, and systems - and potentially even beyond, on the level of psychology. Neuronal development is a lengthy process, a fact that must be considered when judging causes and consequences in experiments that address function and function-dependent regulation of adult neurogenesis. Nevertheless, the information that has been obtained and published so far provides ample evidence that neurons generated in the adult can function and even suggests how they might contribute to cognitive processes.}, Author = {Kempermann, Gerd and Wiskott, Laurenz and Gage, Fred H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Aging;01 Adult neurogenesis general;Cell Differentiation;Adult;Nerve Regeneration;Human;Neuronal Plasticity;Stem Cells;Cell Division;review, tutorial;Animals;Brain;review;Neurons}, Month = {4}, Nlm_Id = {9111376}, Number = {2}, Organization = {Max Delbr{\"u}ck Center for Molecular Medicine, Berlin-Buch and Volkswagenstiftung Research Group at the Department of Experimental Neurology, Charit{\'e} - University Medicine Berlin, Berlin, Germany.}, Pages = {186-91}, Pii = {S0959438804000339}, Pubmed = {15082323}, Title = {Functional significance of adult neurogenesis}, Uuid = {F0AA4D53-BD0E-4090-8D66-893A3B7AF074}, Volume = {14}, Year = {2004}, url = {papers/Kempermann_CurrOpinNeurobiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2004.03.001}} @article{Kempermann:1998a, Abstract = {We demonstrate here that under physiological conditions neurogenesis continues to occur in the dentate gyrus of senescent mice and can be stimulated by living in an enriched environment. Neurogenesis was investigated by confocal microscopy of three-channel immunofluorescent staining for the proliferation marker bromodeoxyuridine (BrdU) and neuronal and glial markers. Quantification was performed with unbiased stereological counting techniques. Neurogenesis decreased with increasing age. Stimulation of adult and aged mice by switching from standard housing to an enriched environment with opportunities for social interaction, exploration, and physical activity for 68 d resulted in an increased survival of labeled cells. Phenotypic analysis revealed that, in enriched living animals, relatively more cells differentiated into neurons, resulting in a threefold net increase of BrdU-labeled neurons in 20-month-old mice (105 vs 32 cells) and a more than twofold increase in 8-month-old mice (684 vs 285 cells) compared with littermates living under standard laboratory conditions. Corresponding absolute numbers of BrdU-positive astrocytes and BrdU- positive cells that did not show colabeling for neuronal or glial markers were not influenced. The effect on the relative distribution of phenotypes can be interpreted as a survival-promoting effect that is selective for neurons. Proliferation of progenitor cells appeared unaffected by environmental stimulation.}, Author = {Kempermann, G. and Kuhn, H. G. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci}, Keywords = {Neurons/*cytology;Microscopy, Confocal;Phenotype;Female;Cell Count;C abstr;Animal;Mice, Inbred C57BL;Aging/*physiology;DNA/metabolism;Support, Non-U.S. Gov't;Dentate Gyrus/*physiology;Cell Division/physiology;Maze Learning/physiology;Support, U.S. Gov't, P.H.S.;Nerve Tissue/*growth &development;04 Adult neurogenesis factors;Mice;Immunohistochemistry;Bromodeoxyuridine}, Number = {9}, Organization = {The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA.}, Pages = {3206-12.}, Title = {Experience-induced neurogenesis in the senescent dentate gyrus}, Uuid = {275CF215-A8A7-4495-AB0A-FAF51B763BBC}, Volume = {18}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9547229}} @article{Kempermann:2002, Author = {Kempermann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;Cell Division/physiology;Hippocampus/*cytology/growth &development/physiology;Adaptation, Physiological/physiology;Neurons/*cytology/physiology;Human;Nerve Net/cytology/physiology;A both;Animal;Memory/physiology}, Number = {3}, Organization = {Research Group VolkswagenStiftung at the Department of Experimental Neurology, Charite University Hospital, Humboldt University Berlin, 10117 Berlin, Germany. gerd.kempermann\@mdc-berlin.de}, Pages = {635-8.}, Title = {Why new neurons? Possible functions for adult hippocampal neurogenesis}, Uuid = {03C2536B-8172-4F8F-A2DC-0AC6D4E571AC}, Volume = {22}, Year = {2002}, url = {papers/Kempermann_JNeurosci2002.pdf}} @article{Kempermann:1998b, Author = {Kempermann, G. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Nat Med}, Keywords = {01 Adult neurogenesis general;Cell Differentiation;A abstr;Cell Division;Animal;Neurons/*cytology;Callithrix;Dentate Gyrus/*cytology/growth &development;Stem Cells/*cytology}, Number = {5}, Pages = {555-7.}, Title = {Closer to neurogenesis in adult humans}, Uuid = {6CDD6AE1-439C-4E14-8F23-D48FA4F12734}, Volume = {4}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9585224}} @article{Kempermann:1997, Abstract = {Neurogenesis occurs in the dentate gyrus of the hippocampus throughout the life of a rodent, but the function of these new neurons and the mechanisms that regulate their birth are unknown. Here we show that significantly more new neurons exist in the dentate gyrus of mice exposed to an enriched environment compared with littermates housed in standard cages. We also show, using unbiased stereology, that the enriched mice have a larger hippocampal granule cell layer and 15 per cent more granule cell neurons in the dentate gyrus.}, Author = {Kempermann, G. and Kuhn, H. G. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Nature}, Keywords = {Dentate Gyrus/*cytology;Female;Housing, Animal;Cell Division;Cell Count;*Environment;Animal;04 Adult neurogenesis factors;Neurons/*cytology;Maze Learning;Support, Non-U.S. Gov't;Bromodeoxyuridine;Mice;C abstr}, Number = {6624}, Organization = {The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA.}, Pages = {493-5.}, Title = {More hippocampal neurons in adult mice living in an enriched environment}, Uuid = {4833BE8D-AF4F-4A87-A75A-24A777D63B80}, Volume = {386}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9087407}} @article{Kempermann:1997a, Abstract = {To address genetic influences on hippocampal neurogenesis in adult mice, we compared C57BL/6, BALB/c, CD1(ICR), and 129Sv/J mice to examine proliferation, survival, and differentiation of newborn cells in the dentate gyrus. Proliferation was highest in C57BL/6; the survival rate of newborn cells was highest in CD1. In all strains approximately 60\%of surviving newborn cells had a neuronal phenotype, but 129/SvJ produced more astrocytes. Over 6 days C57BL/6 produced 0.36\%of their total granule cell number of 239,000 as new neurons, BALB/c 0.30\%of 242,000, CD1 (ICR) 0.32\%of 351,000, and 129/SvJ 0.16\%of 280,000. These results show that different aspects of adult hippocampal neurogenesis are differentially influenced by the genetic background.}, Author = {Kempermann, G. and Kuhn, H. G. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Mice, Inbred BALB C;Cell Survival;Cell Differentiation;Microscopy, Confocal;Comparative Study;Dentate Gyrus/cytology/*growth &development/metabolism;Animal;C abstr;Mice, Inbred C57BL;Species Specificity;Mice, Inbred ICR;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Neurons/cytology;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Immunohistochemistry}, Number = {19}, Organization = {Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.}, Pages = {10409-14.}, Title = {Genetic influence on neurogenesis in the dentate gyrus of adult mice}, Uuid = {A5D2FF94-6417-4930-A432-11C53EACA67C}, Volume = {94}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9294224}} @article{Kempermann:2000, Abstract = {Plasticity is an essential characteristic of the brain: it is part of how the brain functions and is continuous while the brain interacts with the outer world. The state of activation and the level of activity of the entire organism affect the brain's plastic response. Brain plasticity has many substrates, ranging from synapses to neurites and entire cells. The production of new neurons is part of plasticity even in the adult and old brain, but under normal conditions neurogenesis only occurs in two privileged regions of the adult brain: hippocampus and olfactory system. At least in the hippocampus, physical activity stimulates neurogenesis by acting on the proliferation of neuronal stem cells. More specific functions such as learning may be able to recruit new neurons from the pool of cells with neurogenic potential. In a broader context neuronal stem cells can likely be found throughout the brain. Therefore, novel approaches to neuroregeneration will, when most effective, make use of the activity-related effects on neuronal stem cells in the adult brain to activate these stem cells in a targeted manner to enhance brain function. Using Smart Source Parsing}, Author = {Kempermann, G. and van Praag, H. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Prog Brain Res}, Keywords = {Support, U.S. Gov't, P.H.S.;Animal;Cell Division/physiology;Nerve Regeneration/*physiology;Human;Stem Cells/cytology/physiology/*transplantation;Exercise Therapy/trends;Neuronal Plasticity/*physiology;Brain Injuries/*therapy;Physical Conditioning, Animal/physiology;Central Nervous System/cytology/*embryology/physiology;04 Adult neurogenesis factors;Support, Non-U.S. Gov't;Hippocampus/cytology/growth &development/physiology;Cell Differentiation/physiology;C abstr;Tissue Transplantation/methods/*trends}, Organization = {Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.}, Pages = {35-48}, Title = {Activity-dependent regulation of neuronal plasticity and self repair}, Uuid = {8182F0DE-60A3-4BAA-9C52-1945425C61D0}, Volume = {127}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11142036}} @article{Kempermann:2003, Author = {Kempermann, Gerd and Neumann, Harald}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Cell Differentiation;Signal Transduction;Animals;comment;Anti-Inflammatory Agents, Non-Steroidal;Rats;Neuronal Plasticity;Brain-Derived Neurotrophic Factor;Microglia;Lipopolysaccharides;Hippocampus;11 Glia;Neurons;Inflammation Mediators;06 Adult neurogenesis injury induced;04 Adult neurogenesis factors;Minocycline;Mice;24 Pubmed search results 2008;Interleukin-6;Stem Cells;Inflammation;Immunity, Natural}, Month = {12}, Nlm_Id = {0404511}, Number = {5651}, Organization = {Neuronal Stem Cells Research Group, Max-Delbr{\"u}ck-Centrum f{\"u}r Molekulare Medizin Berlin-Buch, 13125 Berlin, Germany. gerd.kempermann\@mdc-berlin.de}, Pages = {1689-90}, Pii = {302/5651/1689}, Pubmed = {14657479}, Title = {Neuroscience. Microglia: the enemy within?}, Uuid = {BC9ED3E2-C167-42E5-BD95-D5732CB79340}, Volume = {302}, Year = {2003}, url = {papers/Kempermann_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1092864}} @article{Kenet:2003, Abstract = {Spontaneous cortical activity--ongoing activity in the absence of intentional sensory input--has been studied extensively, using methods ranging from EEG (electroencephalography), through voltage sensitive dye imaging, down to recordings from single neurons. Ongoing cortical activity has been shown to play a critical role in development, and must also be essential for processing sensory perception, because it modulates stimulus-evoked activity, and is correlated with behaviour. Yet its role in the processing of external information and its relationship to internal representations of sensory attributes remains unknown. Using voltage sensitive dye imaging, we previously established a close link between ongoing activity in the visual cortex of anaesthetized cats and the spontaneous firing of a single neuron. Here we report that such activity encompasses a set of dynamically switching cortical states, many of which correspond closely to orientation maps. When such an orientation state emerged spontaneously, it spanned several hypercolumns and was often followed by a state corresponding to a proximal orientation. We suggest that dynamically switching cortical states could represent the brain's internal context, and therefore reflect or influence memory, perception and behaviour.}, Author = {Kenet, Tal and Bibitchkov, Dmitri and Tsodyks, Misha and Grinvald, Amiram and Arieli, Amos}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Visual Cortex;Anesthesia;Visual Perception;21 Neurophysiology;Orientation;Cats;Algorithms;Fluorescent Dyes;Brain Mapping;Animals;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0410462}, Number = {6961}, Organization = {Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel. (tal\@phy.ucsf.edu}, Pages = {954-6}, Pii = {nature02078}, Pubmed = {14586468}, Title = {Spontaneously emerging cortical representations of visual attributes}, Uuid = {0276B215-A4B7-4226-B658-8CA9A103511A}, Volume = {425}, Year = {2003}, url = {papers/Kenet_Nature2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature02078}} @article{Kennedy:1997, Abstract = {To determine the kinetics of tissue macrophage and microglial engraftment after bone marrow (BM) transplantation, we have developed a model using the ROSA 26 mouse. Transplanted ROSA 26 cells can be precisely identified in recipient animals because they constitutively express beta-galactosidase (beta-gal) and neomycin resistance. B6/129 F2 mice were irradiated and transplanted with BM from ROSA 26 donors and their tissues (spleen, marrow, brain, liver, and lung) examined at various time points to determine the kinetics of engraftment. Frozen sections from transplanted animals were stained histochemically for beta-gal to identify donor cells. At 1, 2, 6, and 12 months posttransplantation, 98\%to 100\%of granulocyte-macrophage colonies were of donor (ROSA 26) origin determined by beta-gal staining and by neomycin resistance. Splenic monocytes/macrophages were 89\%donor origin by 1 month confirming quick and complete engraftment of hematopoietic tissues. At this time, only rare ROSA 26 tissue macrophages or microglia were observed. Alveolar macrophage engraftment was evident by 2 months and had increased to 61\%of total tissue macrophages at 1 year posttransplantation. The kinetics of liver Kupffer cell engraftment were similar to those seen in the lung. However, donor microglial engraftment remained only 23\%of total microglia at 6 months and increased to only 30\%by 1 year. Also, donor microglia were predominantly seen at perivascular and leptomeningeal, and not parenchymal, sites. The data show that microglia derive from BM precursors but turn over at a significantly slower rate than other tissue macrophages. No clinical or histological graft-versus-host disease was observed in the recipients of ROSA 26 BM. These kinetics may impact strategies for the gene therapy of lysosomal storage diseases. Because individual donor cells can be identified in situ, the ROSA 26 model should have many applications in transplantation biology including studies of homing and differentiation.}, Author = {Kennedy, D. W. and Abkowitz, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Genetic Markers;beta-Galactosidase;Macrophages, Alveolar;Colony-Forming Units Assay;Macrophages;Lysosomal Storage Diseases;Bone Marrow Transplantation;Humans;Animals;Microglia;Female;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Time Factors;Radiation Chimera;Male;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;Gene Therapy;Mice;Central Nervous System;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {97385032}, Month = {8}, Nlm_Id = {7603509}, Number = {3}, Organization = {Division of Hematology, University of Washington, Seattle 98195, USA.}, Pages = {986-93}, Pubmed = {9242527}, Title = {Kinetics of central nervous system microglial and macrophage engraftment: analysis using a transgenic bone marrow transplantation model}, Uuid = {70684331-D5C8-4461-9266-81DF6D78A932}, Volume = {90}, Year = {1997}} @article{Kennedy:2003, Abstract = {Genetic factors play a major role in the etiology of adult-onset neurodegenerative and neuropsychiatric disorders. Several highly penetrant genes have been cloned for rare, autosomal-dominant, early-onset forms of neurodegenerative diseases. These genes have provided important insights into the mechanisms of these diseases (often altering neuronal protein processing). However, the genes associated with inherited susceptibility to late-onset neurodegenerative diseases, schizophrenia, and bipolar disorder appear to have smaller effects and are likely to interact with each other (and with nongenetic factors) to modulate susceptibility and/or disease phenotype. Several strategies have recently been applied to address this complexity, leading to the identification of a number of candidate susceptibility loci/genes.}, Author = {Kennedy, James L. and Farrer, Lindsay A. and Andreasen, Nancy C. and Mayeux, Richard and St George-Hyslop, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:50 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Human;Middle Aged;Bipolar Disorder;review, tutorial;Phenotype;review;Schizophrenia;21 Neurodegenerative;Genetic Predisposition to Disease;Neuregulin-1;Mental Disorders;Linkage (Genetics);Alzheimer Disease;Support, Non-U.S. Gov't;21 Neurophysiology;Adult;Genetic Heterogeneity;Support, U.S. Gov't, P.H.S.;Multifactorial Inheritance;Dementia;Chromosome Mapping;Neurodegenerative Diseases}, Medline = {22954845}, Month = {10}, Nlm_Id = {0404511}, Number = {5646}, Organization = {Departments of Psychiatry and Medicine, Centre for Addiction and Mental Health, Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario M5S 3H9, Canada.}, Pages = {822-6}, Pii = {302/5646/822}, Pubmed = {14593167}, Title = {The genetics of adult-onset neuropsychiatric disease: complexities and conundra?}, Uuid = {C034899D-793E-4248-9EDE-6C22556F796F}, Volume = {302}, Year = {2003}, url = {papers/Kennedy_Science2003.pdf}, Bdsk-File-2 = {papers/Kennedy_Science2003a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1092132}} @article{Kerjan:2007, Abstract = {Classical lissencephaly is a human developmental brain disorder characterized by a paucity of cortical gyration and thickening of the cortical gray matter, leading to severe epilepsy and mental retardation. Loss-of-function mutations in the microtubule-associated protein encoding genes, PAFAH1B1 (encoding the protein LIS1), DCX and TUBA1A have been implicated in the pathogenesis of the condition. Animal models are required to understand the basis of this disease, which is a challenge, given that mice normally have a smooth cortex. Recent advances toward this goal have come from stepwise reduction in gene function, deletion of redundant genes and acute gene inactivation using short hairpin RNA (shRNA). These approaches have implicated genes that regulate the microtubule cytoskeleton during neuronal division, migration and maturation.}, Author = {Kerjan, Geraldine and Gleeson, Joseph G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0168-9525}, Journal = {Trends Genet}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8507085}, Number = {12}, Organization = {Neurogenetics Laboratory, Department of Neurosciences, LBR3A16, UCSD School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0691, USA.}, Pages = {623-30}, Pii = {S0168-9525(07)00328-9}, Pubmed = {17997185}, Title = {Genetic mechanisms underlying abnormal neuronal migration in classical lissencephaly}, Uuid = {6C8EAF1F-EDFC-412C-B2FF-E8EE0E49B366}, Volume = {23}, Year = {2007}, url = {papers/Kerjan_TrendsGenet2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tig.2007.09.003}} @article{Kernie:2001, Abstract = {The persistence of neural stem cells into adulthood has been an area of intense investigation in recent years. There is limited knowledge about how an acquired brain injury might affect the ability of neural precursor cells to proliferate and repopulate injured areas. In the present study we utilize a controlled cortical impact model of traumatic brain injury in adult mice and subsequent BrdU labeling to demonstrate that there is significant proliferation of neural precursors in response to traumatic brain injury in areas both proximal and distal to the injury site. The fate of the proximal proliferation is almost exclusively astrocytic at 60-days post injury and demonstrates that newly generated cells make up much of the astrogliotic scar. Moreover, in areas more distal from the injury site, neurogenesis occurs within the granular layer of the dentate gyrus at a level more than five-fold greater than in controls. These data demonstrate that neural proliferation plays key roles in the remodeling that occurs after traumatic brain injury and suggests a mechanism as to how functional recovery after traumatic brain injuries continues to occur long after the injury itself.}, Author = {Kernie, S. G. and Erwin, T. M. and Parada, L. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Intermediate Filament Proteins/metabolism;Support, Non-U.S. Gov't;Nerve Tissue Protein S 100/metabolism;06 Adult neurogenesis injury induced;Astrocytes;Dentate Gyrus;Up-Regulation/physiology;Disease Models, Animal;Recovery of Function;Brain Injuries/*physiopathology;Male;Up-Regulation;24 Pubmed search results 2008;Cerebral Cortex;Immunohistochemistry;Nerve Regeneration;Research Support, Non-U.S. Gov't;Recovery of Function/physiology;Animals;Mice, Inbred Strains;Astrocytes/cytology/*metabolism;Cell Division/*physiology;Intermediate Filament Proteins;Bromodeoxyuridine;Cell Division;Calcium-Binding Protein, Vitamin D-Dependent;Nerve Regeneration/*physiology;Gliosis;Neuronal Plasticity;Cerebral Cortex/cytology/injuries/metabolism;Animal;Glial Fibrillary Acidic Protein;D pdf;Dentate Gyrus/cytology/metabolism;Neurons/cytology/*metabolism;Calcium-Binding Protein, Vitamin D-Dependent/metabolism;Bromodeoxyuridine/diagnostic use/metabolism;Stem Cells/cytology/*metabolism;Stem Cells;S100 Proteins;Glial Fibrillary Acidic Protein/metabolism;Mice;Neuronal Plasticity/physiology;Brain Injuries;Nerve Tissue Proteins;Neurons;Gliosis/etiology/*physiopathology}, Medline = {21611761}, Month = {11}, Nlm_Id = {7600111}, Number = {3}, Organization = {Center for Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9133, USA. Steven.Kernie\@utsouthwestern.edu}, Pages = {317-26.}, Pii = {10.1002/jnr.10013}, Pubmed = {11746349}, Title = {Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice}, Uuid = {702B0430-E8A9-46C1-8A06-9744D5668C95}, Volume = {66}, Year = {2001}, url = {papers/Kernie_JNeurosciRes2001}} @article{Kerr:2007, Abstract = {Individual pyramidal neurons of neocortex show sparse and variable responses to sensory stimuli in vivo. It has remained unclear how this variability extends to population responses on a trial-to-trial basis. Here, we characterized single-neuron and population responses to whisker stimulation in layer 2/3 (L2/3) of identified columns in rat barrel cortex using in vivo two-photon calcium imaging. Optical detection of single action potentials from evoked calcium transients revealed low spontaneous firing rates (0.25 Hz), variable response probabilities (range, 0-0.5; mean, 0.2 inside barrel column), and weak angular tuning of L2/3 neurons. On average, both the single-neuron response probability and the percentage of the local population activated were higher in the barrel column than above septa or in neighboring columns. Within the barrel column, mean response probability was highest in the center (0.4) and declined toward the barrel border. Neuronal pairs showed correlations in both spontaneous and sensory-evoked activity that depended on the location of the neurons. Correlation decreased with increasing distance between neurons and, for neuronal pairs the same distance apart, with distance of the pair from the barrel column center. Although neurons are therefore not activated independently from each other, we did not observe precisely repeating spatial activation patterns. Instead, population responses showed large trial-to-trial variability. Nevertheless, the accuracy of decoding stimulus onset times from local population activity increased with population size and depended on anatomical location. We conclude that, despite their sparseness and variability, L2/3 population responses show a clear spatial organization on the columnar scale.}, Author = {Kerr, Jason N. D. and de Kock, Christiaan P. J. and Greenberg, David S. and Bruno, Randy M. and Sakmann, Bert and Helmchen, Fritjof}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Statistics as Topic;Electric Stimulation;Animals;Image Processing, Computer-Assisted;Rats;Patch-Clamp Techniques;Vibrissae;Rats, Wistar;Calcium;Organic Chemicals;Animals, Newborn;Action Potentials;Evoked Potentials, Somatosensory;Neurons;Somatosensory Cortex;Probability;24 Pubmed search results 2008;Brain Mapping}, Month = {11}, Nlm_Id = {8102140}, Number = {48}, Organization = {Department of Cell Physiology, Max Planck Institute for Medical Research, D-69120 Heidelberg, Germany. jason\@tuebingen.mpg.de}, Pages = {13316-28}, Pii = {27/48/13316}, Pubmed = {18045926}, Title = {Spatial organization of neuronal population responses in layer 2/3 of rat barrel cortex}, Uuid = {BA289ECF-C46D-4442-9D54-CD92F69B470A}, Volume = {27}, Year = {2007}, url = {papers/Kerr_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2210-07.2007}} @article{Kerr:2008, Abstract = {The appeal of in vivo cellular imaging to any neuroscientist is not hard to understand: it is almost impossible to isolate individual neurons while keeping them and their complex interactions with surrounding tissue intact. These interactions lead to the complex network dynamics that underlie neural computation which, in turn, forms the basis of cognition, perception and consciousness. In vivo imaging allows the study of both form and function in reasonably intact preparations, often with subcellular spatial resolution, a time resolution of milliseconds and a purview of months. Recently, the limits of what can be achieved in vivo have been pushed into terrain that was previously only accessible in vitro, due to advances in both physical-imaging technology and the design of molecular contrast agents.}, Author = {Kerr, Jason N. D. and Denk, Winfried}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1471-0048}, Journal = {Nat Rev Neurosci}, Keywords = {Magnetic Resonance Imaging;Image Processing, Computer-Assisted;Models, Neurological;Brain Mapping;Animals;Brain;Humans;review;Neurons;calcium imaging;technique;optical physiology;optical imaging;multiphoton;microscopy;Optics;frontiers review}, Month = {3}, Nlm_Id = {100962781}, Number = {3}, Organization = {Network Imaging Group, Max Planck Institute for Biological Cybernetics, Spemannstrasse 41, D-72076 Tuebingen, Germany. jason\@tuebingen.mpg.de}, Pages = {195-205}, Pii = {nrn2338}, Pubmed = {18270513}, Title = {Imaging in vivo: watching the brain in action}, Uuid = {1702B0AE-A4B5-4307-AA80-B68EA555E602}, Volume = {9}, Year = {2008}, url = {papers/Kerr_NatRevNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn2338}} @article{Kerr:2005, Abstract = {Neural activity manifests itself as complex spatiotemporal activation patterns in cell populations. Even for local neural circuits, a comprehensive description of network activity has been impossible so far. Here we demonstrate that two-photon calcium imaging of bulk-labeled tissue permits dissection of local input and output activities in rat neocortex in vivo. Besides astroglial and neuronal calcium transients, we found spontaneous calcium signals in the neuropil that were tightly correlated to the electrocorticogram. This optical encephalogram (OEG) is shown to represent bulk calcium signals in axonal structures, thus providing a measure of local input activity. Simultaneously, output activity in local neuronal populations could be derived from action potential-evoked calcium transients with single-spike resolution. By using these OEG and spike activity measures, we characterized spontaneous activity during cortical Up states. We found that (i) spiking activity is sparse (<0.1 Hz); (ii) on average, only approximately 10\%of neurons are active during each Up state; (iii) this active subpopulation constantly changes with time; and (iv) spiking activity across the population is evenly distributed throughout the Up-state duration. Furthermore, the number of active neurons directly depended on the amplitude of the OEG, thus optically revealing an input-output function for the local network. We conclude that spontaneous activity in the neocortex is sparse and heterogeneously distributed in space and time across the neuronal population. The dissection of the various signal components in bulk-loaded tissue as demonstrated here will enable further studies of signal flow through cortical networks.}, Author = {Kerr, Jason N. D. and Greenberg, David and Helmchen, Fritjof}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Microscopy, Confocal;Electroencephalography;Neuropil;21 Neurophysiology;Action Potentials;Rats;Neocortex;Photons;Nerve Net;Animals;Calcium Signaling;Neurons;Axons}, Month = {9}, Nlm_Id = {7505876}, Number = {39}, Organization = {Department of Cell Physiology, Max Planck Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany.}, Pages = {14063-8}, Pii = {0506029102}, Pubmed = {16157876}, Title = {Imaging input and output of neocortical networks in vivo}, Uuid = {9867358D-2C22-476C-9B8A-87CBF747A7D7}, Volume = {102}, Year = {2005}, url = {papers/Kerr_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0506029102}} @article{Kesslak:1986, Abstract = {Ablation of the medial frontal cortex produces a learning deficit on a reinforced alternation task. Recovery from this deficit was significantly accelerated in rats by transplantation of either cultured purified astrocytes or Gelfoam that had remained the previous 5 days in a brain wound in another animal (wound-Gelfoam). Cell-free extracts of wound-Gelfoam did not enhance behavioral recovery. Embryonic frontal cortex was effective only if transplanted with a delay after ablation. It appears from these results that transplants can facilitate functional recovery by more than one mechanism, including promotion of survival and reactive synaptogenesis of host neurons, stabilization of the damaged environment and replacement of lost neurons. In this study, glial cells were capable of facilitating recovery from central nervous system damage to the same extent as neuronal transplants.}, Author = {Kesslak, J. P. and Nieto-Sampedro, M. and Globus, J. and Cotman, C. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:33 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Gelatin Sponge, Absorbable;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Behavior, Animal;Movement;Rats;Research Support, U.S. Gov't, P.H.S.;Astrocytes;Learning;Male;Cells, Cultured;Rats, Inbred Strains;Animals;Frontal Lobe}, Medline = {86164810}, Month = {5}, Nlm_Id = {0370712}, Number = {2}, Pages = {377-90}, Pubmed = {3956668}, Title = {Transplants of purified astrocytes promote behavioral recovery after frontal cortex ablation}, Uuid = {4ABC6829-ABC4-4956-958A-0EEB9CAC907F}, Volume = {92}, Year = {1986}} @article{Kettenmann:1990, Abstract = {Microglia are the source of the resident macrophages of the brain and thus belong to one of the most reactive cell types in cerebral tissue. They are attributed to have an important role in a number of pathological conditions, such as multiple sclerosis, viral infections like AIDS, and in lethal or sublethal injuries of neurons where the blood-brain barrier is left intact (Streit et al., 1988; McGeer et al., 1988; Gendelman et al., 1989). Microglia share a number of macrophage characteristics but so far lack a distinguishing positive marker. In this study it is shown that microglia are distinguished from other macrophages by a unique pattern of ion channels. We compared membrane currents of microglial cells with those from peritoneal macrophages cultured under identical conditions. Although in macrophages a delayed outward K+ current was previously described (Randriamampita and Trautmann, 1987), microglial cells lacked any specific outward current. Instead, these cells were characterized by large inwardly rectifying currents, activated by hyperpolarizing voltage steps. The reversal potential in different K+ gradients and the sensitivity of the current to to Ba2+, TEA, and 4-AP indicates that this current is K+ selective. In single-channel recordings, a 30 pS K+ selective channel similar to the classical inward rectifier K+ channel was observed. Thus, the expression of membrane channels served not only to distinguish microglia from other cells inside and outside the brain, e.g., blood macrophages, but also suggests a unique functional state of this cell population.}, Author = {Kettenmann, H. and Hoppe, D. and Gottmann, K. and Banati, R. and Kreutzberg, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Support, Non-U.S. Gov't;Potassium;Ion Channels;Peritoneal Cavity;Not relevant;11 Glia;Macrophages;Electrophysiology;Cells, Cultured;Potassium Channels;Brain;Membrane Potentials;Animals}, Medline = {90376370}, Month = {7}, Nlm_Id = {7600111}, Number = {3}, Organization = {Department of Neurobiology, University of Heidelberg, Federal Republic of Germany.}, Pages = {278-87}, Pubmed = {1697905}, Title = {Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages}, Uuid = {DD16A7BA-6A0D-4274-AD98-AF4AFAB59673}, Volume = {26}, Year = {1990}} @article{Kettenmann:2007, Author = {Kettenmann,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {0410462}, Organization = {Helmut Kettenmann is at the Max Delbr{\"u}ck Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13092 Berlin, Germany.kettenmann\@mdc-berlin.de.}, Pii = {nature05713}, Pubmed = {17410127}, Title = {Neuroscience: The brain's garbage men}, Uuid = {348AD2EC-2AC4-4078-B6E2-9F6A5E96D50D}, Year = {2007}, url = {papers/Kettenmann_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05713}} @article{Khalilov:1999, Abstract = {The effects of modulators of GABA-A receptors on neuronal network activity were studied in the neonatal (postnatal days 0-5) rat hippocampus in vitro. Under control conditions, the physiological pattern of activity of the neonatal hippocampal network was characterized by spontaneous network-driven giant depolarizing potentials (GDPs). The GABA-A receptor agonist isoguvacine (1-2 microM) and the allosteric modulator diazepam (2 microM) induced biphasic responses: initially the frequency of GDPs increased 3 to 4 fold followed by blockade of GDPs and desynchronization of the network activity. The GABA-A receptor antagonists bicuculline (10 microM) and picrotoxin (100 microM) blocked GDPs and induced glutamate (AMPA and NMDA)-receptor-mediated interictal- and ictal-like activities in the hippocampal slices and the intact hippocampus. These data suggest that at early postnatal ages GABA can exert a dual - both excitatory and inhibitory - action on the network activity. Copyright Copyright 1999 S. Karger AG, Basel}, Author = {Khalilov, I. and Dzhala, V. and Ben-Ari, Y. and Khazipov, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {gamma-Aminobutyric Acid;GABA Agonists;Diazepam;Electrophysiology;Animals;In Vitro;Rats;21 Epilepsy;Isonicotinic Acids;Hippocampus;Rats, Wistar;Bicuculline;Animals, Newborn;Nerve Net;21 Neurophysiology;GABA Antagonists;GABA Modulators;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {20044654}, Month = {11}, Nlm_Id = {7809375}, Number = {3-5}, Organization = {INMED, Marseille, France.}, Pages = {310-9}, Pii = {dne21310}, Pubmed = {10575254}, Title = {Dual role of GABA in the neonatal rat hippocampus}, Uuid = {EB4DCB0D-3F38-4839-BC20-78C97F1FE022}, Volume = {21}, Year = {1999}} @article{Khalilov:1999a, Abstract = {In vivo studies suggest that ontogenesis of limbic seizures is determined by the development of the limbic circuit. We have now used the newly-developed in vitro intact interconnected neonatal rat limbic structures preparation to determine the developmental profile of kainate-induced epileptiform activity in the hippocampus and its propagation to other limbic structures. We report gradual alterations in the effects of kainate during the first postnatal week on an almost daily basis; from no epileptiform activity at birth, through interictal seizures around postnatal day (P) 2 and ictal seizures by the end of the first week. The developmental profile of kainate-induced hippocampal seizures is paralleled by the expression of postsynaptic kainate receptor-mediated currents in CA3 pyramidal cells. Intralimbic propagation of the hippocampal seizures is also age-dependent: whereas seizures readily propagate to the septum and to the contralateral hippocampus via the commissures on P2, propagation to the entorhinal cortex only takes place from P4 onwards. Finally, repeated brief applications of kainate to the hippocampus induce recurrent spontaneous glutamatergic ictal and interictal discharges which persist for several hours after the kainate is washed away and which replace the physiological pattern of network activity. Paroxysmal activities are thus generated by kainate in the hippocampus at an early developmental stage and are initially restricted to this structure. Before the end of the first week of postnatal life, kainate generates the epileptiform activities that may perturb activity-dependent mechanisms that modulate neuronal development. Although at this stage neurons are relatively resistant to the pathological effects of kainate, the epileptiform activities that it generates will perturb activity-dependent mechanisms that modulate neuronal development.}, Author = {Khalilov, I. and Dzhala, V. and Medina, I. and Leinekugel, X. and Melyan, Z. and Lamsa, K. and Khazipov, R. and Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Electrophysiology;Animals;Synapses;In Vitro;Rats;21 Epilepsy;Excitatory Amino Acid Agonists;Epilepsy;Entorhinal Cortex;Hippocampus;Rats, Wistar;Calcium;Tetrodotoxin;Kainic Acid;Septal Nuclei;Organ Culture Techniques;Male;Potassium;Animals, Newborn;21 Neurophysiology;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;Benzodiazepines;Limbic System;Research Support, Non-U.S. Gov't}, Medline = {20032200}, Month = {10}, Nlm_Id = {8918110}, Number = {10}, Organization = {INMED, INSERM U 29, Marseille, France.}, Pages = {3468-80}, Pii = {ejn768}, Pubmed = {10564355}, Title = {Maturation of kainate-induced epileptiform activities in interconnected intact neonatal limbic structures in vitro}, Uuid = {DE86AC92-C6A8-445E-9F83-9148203258E8}, Volume = {11}, Year = {1999}} @article{Khalilov:2002, Abstract = {Kainate generates in adult hippocampal neurons a seizure but also a massive excitation of interneurons and a dramatic increase of the inhibitory drive that impinges on principal cells. This "overinhibition" is largely mediated by GluR5-containing kainate receptors that are enriched on interneurons. Here, using the neonatal intact hippocampus in vitro and the triple chamber, we first show that this mechanism is fully operative in neonatal neurons. We then report that application to one hippocampus of (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid-a relatively selective agonist of GluR5 containing kainate receptors-depresses the propagation of seizure generated in the opposite hippocampus by a convulsive agent. We conclude that the selective excitation of interneurons by GluR5-containing kainate receptor agonists opens a new therapeutic approach for the epilepsies.}, Author = {Khalilov, Ilgam and Hirsch, June and Cossart, Rosa and Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Research Support, Non-U.S. Gov't;Anticonvulsants;21 Neurophysiology;Hippocampus;Pyramidal Cells;Rats;Seizures;Neural Inhibition;Rats, Wistar;Receptors, Kainic Acid;Animals, Newborn;Interneurons;Animals;Isoxazoles;24 Pubmed search results 2008;Propionates;21 Epilepsy}, Medline = {22086359}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, U29, Marseille, France.}, Pages = {523-7}, Pubmed = {12091575}, Title = {Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors}, Uuid = {448E86CE-42CD-41AC-8579-8E058707BA89}, Volume = {88}, Year = {2002}} @article{Khalilov:2003, Abstract = {We have determined whether seizures generate an epileptogenic focus in distal structures using an in vitro preparation composed of three independent chambers that accommodate two intact hippocampi and their connecting commissures. This enabled us to apply a convulsive agent to one hippocampus, allow the propagation of a given number of seizures to the other side and block the connections reversibly by applying tetrodotoxin (TTX) to the commissural chamber. The propagation of seizures from the kainate-treated side to the naive side transformed the latter into an independent epileptogenic focus that was capable of generating spontaneous and evoked seizures. The induction mechanism required activation of NMDA receptors and the epileptogenic transformation was associated with long-term alterations in GABAergic synapses, which became excitatory because of a shift in the chloride reversal potential, E(Cl). These data indicate that the excitatory actions of GABA may be a fundamental property of epileptogenic structures.}, Author = {Khalilov, Ilgam and Holmes, Gregory L. and Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Research Support, Non-U.S. Gov't;gamma-Aminobutyric Acid;Presynaptic Terminals;Animals;Rats;Neural Pathways;Chloride Channels;Glutamic Acid;Synaptic Transmission;21 Epilepsy;Epilepsy;Hippocampus;Rats, Wistar;Kainic Acid;Disease Models, Animal;Male;Animals, Newborn;21 Neurophysiology;Membrane Potentials;Laterality;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Medline = {22875098}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {Institut de Neurobiologie de la Mediterranee (INMED)-INSERM U29, 163 Route de Luminy, Marseilles 13273, France.}, Pages = {1079-85}, Pii = {nn1125}, Pubmed = {14502289}, Title = {In vitro formation of a secondary epileptogenic mirror focus by interhippocampal propagation of seizures}, Uuid = {1FFC49FD-9E02-416E-85BA-8EBBA0CF0309}, Volume = {6}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1125}} @article{Khalilov:2005, Abstract = {GABA excites immature neurons and inhibits adult ones, but whether this contributes to seizures in the developing brain is not known. We now report that in the developing, but not the adult, hippocampus, seizures beget seizures only if GABAergic synapses are functional. In the immature hippocampus, seizures generated with functional GABAergic synapses include fast oscillations that are required to transform a naive network to an epileptic one: blocking GABA receptors prevents the long-lasting sequels of seizures. In contrast, in adult neurons, full blockade of GABA(A) receptors generates epileptogenic high-frequency seizures. Therefore, purely glutamatergic seizures are not epileptogenic in the developing hippocampus. We suggest that the density of glutamatergic synapses is not sufficient for epileptogenesis in immature neurons; excitatory GABAergic synapses are required for that purpose. We suggest that the synergistic actions of GABA and NMDA receptors trigger the cascades involved in epileptogenesis in the developing hippocampus.}, Author = {Khalilov, Ilgam and Le Van Quyen, Michel and Gozlan, Henri and Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {gamma-Aminobutyric Acid;Cell Aging;Electrophysiology;Animals;Synapses;In Vitro;Aging;Rats;Seizures;21 Epilepsy;Epilepsy;Hippocampus;Rats, Wistar;Male;Animals, Newborn;21 Neurophysiology;Neurons;GABA Antagonists;24 Pubmed search results 2008;Oscillometry;Research Support, Non-U.S. Gov't}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {INMED-INSERM, U 29 Marseille, 163, route de Luminy, 13273 Marseille Cedex 09, France.}, Pages = {787-96}, Pii = {S0896-6273(05)00882-2}, Pubmed = {16337916}, Title = {Epileptogenic actions of GABA and fast oscillations in the developing hippocampus}, Uuid = {E0F3F8E5-749B-4901-B315-D446D2E34EA4}, Volume = {48}, Year = {2005}, url = {papers/Khalilov_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.09.026}} @article{Khapli:2003, Abstract = {Osteoclasts, the multinucleated cells that resorb bone, differentiate from hemopoietic precursors of the monocyte/macrophage lineage in the presence of M-CSF and receptor activator of NF-kappaB ligand (RANKL). In this study we investigated the role of IL-3 in osteoclast differentiation. We show here that IL-3, a cytokine secreted by activated T lymphocytes, inhibits RANKL-induced osteoclast differentiation by a direct action on early osteoclast precursors. Anti-IL-3 Ab neutralized the inhibitory effect of IL-3 on osteoclast differentiation. In addition, IL-3 inhibits TNF-alpha-induced osteoclast differentiation in bone marrow-derived macrophages. However, IL-3 has no inhibitory effect on mature osteoclasts. In osteoclast precursors, IL-3 prevents RANKL-induced nuclear translocation of NF-kappaB by inhibiting the phosphorylation and degradation of IkappaB. RT-PCR analysis revealed that IL-3 down-regulated c-Fos transcription. Interestingly, the osteoclast precursors in the presence of IL-3 showed strong expression of macrophage markers such as Mac-1, MOMA-2, and F4/80. Furthermore, the inhibitory effect of IL-3 on osteoclast differentiation was irreversible, and the osteoclast precursors preincubated in IL-3 were resistant to RANKL action. Thus, our results reveal for the first time that IL-3 acts directly on early osteoclast precursors and irreversibly blocks RANKL-induced osteoclast differentiation by diverting the cells to macrophage lineage.}, Author = {Khapli, Shruti M. and Mangashetti, Latha S. and Yogesha, S. D. and Wani, Mohan R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {Cell Differentiation;Interleukin-3;Ligands;Receptor, Macrophage Colony-Stimulating Factor;NF-kappa B;Animals;Cells, Cultured;Proto-Oncogene Proteins c-fos;Growth Inhibitors;Mice, Inbred BALB C;Proto-Oncogene Proteins;Osteoclasts;Receptors, Cytoplasmic and Nuclear;RNA, Messenger;Macrophages;11 Glia;Membrane Glycoproteins;Tumor Necrosis Factor-alpha;Carrier Proteins;Active Transport, Cell Nucleus;I-kappa B;Cell Lineage;Bone Marrow Cells;Cell Nucleus;Stem Cells;Glycoproteins;Mice;Research Support, Non-U.S. Gov't;Phosphorylation;Humans;Recombinant Proteins;Trans-Activators}, Medline = {22701037}, Month = {7}, Nlm_Id = {2985117R}, Number = {1}, Organization = {National Center for Cell Science, Pune, India.}, Pages = {142-51}, Pubmed = {12816992}, Title = {IL-3 acts directly on osteoclast precursors and irreversibly inhibits receptor activator of NF-kappa B ligand-induced osteoclast differentiation by diverting the cells to macrophage lineage}, Uuid = {678AE7B2-553E-47B0-8FCE-E1418BC17388}, Volume = {171}, Year = {2003}} @article{Kharlamov:1996, Abstract = {We have shown recently in rats that photothrombotic local brain injury that is induced by the intravenous injection of the photosensitive dye rose bengal and skull irradiation with a beam of focused light can trigger the expression of the protein p53 and initiate DNA damage in the area surrounding the thrombotic/necrotic core. We hypothesize that these changes are the signs of injury-induced apoptosis. We used pharmacological tools to characterize the injury-triggered DNA damage that we assayed by TUNEL-labeling, followed by a computer-assisted quantitative analysis. In addition, the morphology of apoptotic cells was visualized by fluorescent staining with propidium iodide. The pharmacological approach included: (a) the inhibition of endonucleases by intracerebroventricular injection of aurintricarboxylic acid (ATA, 20 micrograms/5 microliters); (b) the inhibition of protein synthesis by injecting cycloheximide subcutaneously (2.5 mg/kg); and (c) the blockade of glutamate receptors by injecting 2.5 mg/kg dizolcipine (MK- 801) intravenously. These treatments significantly reduced the number of apoptotic cells that we counted in the area surrounding the necrotic core. The results show that injury-induced DNA damage involved de novo synthesis of proteins and an activation of endonucleases, suggesting the occurrence of apoptosis. In this model, apoptosis was associated with an activation of glutamate receptors. Treatments targeted at halting the apoptotic process might provide protection after stroke or after trauma to the brain.}, Author = {Kharlamov, A. and Uz, T. and Joo, J. Y. and Manev, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Brain Res}, Keywords = {DNA/metabolism;Rats, Sprague-Dawley;Intracranial Embolism and Thrombosis/chemically;*Light;Rats;*Apoptosis;D;Genetic Techniques;Rose Bengal;Animal;06 Adult neurogenesis injury induced;Support, U.S. Gov't, P.H.S.;induced/etiology/*pathology;Support, Non-U.S. Gov't;Propidium;Male;Brain/metabolism/*pathology}, Number = {1-2}, Organization = {Psychiatric Institute, University of Illinois at Chicago 60612, USA.}, Pages = {1-9.}, Title = {Pharmacological characterization of apoptotic cell death in a model of photothrombotic brain injury in rats}, Uuid = {7B3E9F29-D94D-46F9-9EDF-B60FC7D1B444}, Volume = {734}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8896802}} @article{Khatri:2006, Author = {Khatri, Vivek and Ramos, Raddy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Psychophysics;Sensory Deprivation;21 Neurophysiology;Rats;Neural Pathways;comment;Animals;Vibrissae;24 Pubmed search results 2008;review}, Month = {11}, Nlm_Id = {8102140}, Number = {48}, Organization = {Hunter College, 695 Park Avenue, New York, NY 10021, USA. khatri\_vivek\@yahoo.com}, Pages = {12385-6}, Pubmed = {17139795}, Title = {Rat whisker psychophysics}, Uuid = {CF82CA29-DF7B-45D4-9C68-FD61F4851E6B}, Volume = {26}, Year = {2006}} @article{Khazipov:2004, Abstract = {The immature brain is prone to seizures but the underlying mechanisms are poorly understood. We explored the hypothesis that increased seizure susceptibility during early development is due to the excitatory action of GABA. Using noninvasive extracellular field potential and cell-attached recordings in CA3 of Sprague-Dawley rat hippocampal slices, we compared the developmental alterations in three parameters: excitatory actions of GABA, presence of the immature pattern of giant depolarizing potentials (GDPs) and severity of epileptiform activity generated by high potassium. The GABA(A) receptor agonist isoguvacine increased firing of CA3 pyramidal cells in neonatal slices while inhibiting activity in adults. A switch in the GABA(A) signalling from excitation to inhibition occurred at postnatal day (P) 13.5 +/- 0.4. Field GDPs were present in the form of spontaneous population bursts until P12.7 +/- 0.3. High potassium (8.5 mm) induced seizure-like events (SLEs) in 35\%of slices at P7-16 (peak at P11.3 +/- 0.4), but only interictal activity before and after that age. The GABA(A) receptor antagonist bicuculline reduced the frequency or completely blocked SLEs and induced interictal clonic-like activity accompanied by a reduction in the frequency but an increase in the amplitude of the population spikes. In slices with interictal activity, bicuculline typically caused a large amplitude interictal clonic-like activity at all ages; in slices from P5-16 rats it was often preceded by one SLE at the beginning of bicuculline application. These results suggest that, in the immature hippocampus, GABA exerts dual (both excitatory and inhibitory) actions and that the excitatory component in the action of GABA may contribute to increased excitability during early development.}, Author = {Khazipov, Roustem and Khalilov, Ilgam and Tyzio, Roman and Morozova, Elena and Ben-Ari, Yezekiel and Holmes, Gregory L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Excitatory Postsynaptic Potentials;gamma-Aminobutyric Acid;Research Support, Non-U.S. Gov't;Animals;In Vitro;Aging;Rats;Comparative Study;Seizures;21 Epilepsy;Patch-Clamp Techniques;Female;Isonicotinic Acids;Hippocampus;Pyramidal Cells;Disease Susceptibility;Time Factors;Bicuculline;Male;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Potassium;21 Neurophysiology;Membrane Potentials;GABA Antagonists;24 Pubmed search results 2008;Neural Inhibition;GABA Agonists}, Month = {2}, Nlm_Id = {8918110}, Number = {3}, Organization = {Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, New Hampshire, 03756, USA. khazipov\@inmed.univ-mrs.fr}, Pages = {590-600}, Pii = {3152}, Pubmed = {14984409}, Title = {Developmental changes in GABAergic actions and seizure susceptibility in the rat hippocampus}, Uuid = {B90CF51D-3E5A-4DC4-B80E-B76E32F8F276}, Volume = {19}, Year = {2004}} @article{Khazipov:1999, Abstract = {We describe a novel chamber in which the two intact neonatal rat hippocampi and the commissural fibers are placed in three independent compartments separated by latex membranes and perfused selectively with different solutions. A set of control tests showed that the compartments are well isolated: 1) methylene blue or eosin applied to one compartment did not diffuse to other compartments when verified via the microscope, and spectrophotometry revealed that <1/10.000th of the dye diffuses to other compartments; 2) tetrodotoxin (1 microM) applied to the commissural compartment blocked the synaptic responses evoked contralaterally without affecting those evoked on the ipsilateral side. This chamber enables a wide range of experiments that cannot be performed in conventional chambers, e.g., to study the maturation and plasticity of the commissural connections, bilateral synchronization of the rhythmic activities in the limbic system, commissural propagation of the epileptiform activities, etc.}, Author = {Khazipov, R. and Desfreres, L. and Khalilov, I. and Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Synapses;Perfusion;21 Neurophysiology;Eosine Yellowish-(YS);Rats;Hippocampus;Rats, Wistar;In Vitro;Tetrodotoxin;Animals, Newborn;Culture Techniques;Membranes, Artificial;Animals;Latex;Methylene Blue;24 Pubmed search results 2008;21 Epilepsy}, Medline = {99158870}, Month = {2}, Nlm_Id = {0375404}, Number = {2}, Organization = {Centre de Recherches sur l'Epilepsie et l'Isch{\'e}mie C{\'e}r{\'e}brale, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U29, 123 Bd de Port-Royal, Paris 75674, France.}, Pages = {921-4}, Pubmed = {10036300}, Title = {Three-independent-compartment chamber to study in vitro commissural synapses}, Uuid = {91E01962-F1BD-4B12-BF35-6D26045896D0}, Volume = {81}, Year = {1999}} @article{Khazipov:2001, Abstract = {Morphological studies suggest that the primate hippocampus develops extensively before birth, but little is known about its functional development. Patch-clamp recordings of hippocampal neurons and reconstruction of biocytin-filled pyramidal cells were performed in slices of macaque cynomolgus fetuses delivered by cesarean section. We found that during the second half of gestation, axons and dendrites of pyramidal cells grow intensively by hundreds of micrometers per day to attain a high level of maturity near term. Synaptic currents appear around midgestation and are correlated with the level of morphological differentiation of pyramidal cells: the first synapses are GABAergic, and their emergence correlates with the growth of apical dendrite into stratum radiatum. A later occurrence of glutamatergic synaptic currents correlates with a further differentiation of the axodendritic tree and the appearance of spines. Relying on the number of dendritic spines, we estimated that hundreds of new glutamatergic synapses are established every day on a pyramidal neuron during the last third of gestation. Most of the synaptic activity is synchronized in spontaneous slow ( approximately 0.1 Hz) network oscillations reminiscent of the giant depolarizing potentials in neonatal rodents. Epileptiform discharges can be evoked by the GABA(A) receptor antagonist bicuculline by the last third of gestation, and postsynaptic GABA(B) receptors contribute to the termination of epileptiform discharges. Comparing the results obtained in primates and rodents, we conclude that the template of early hippocampal network development is conserved across the mammalian evolution but that it is shifted toward fetal life in primate.}, Author = {Khazipov, R. and Esclapez, M. and Caillard, O. and Bernard, C. and Khalilov, I. and Tyzio, R. and Hirsch, J. and Dzhala, V. and Berger, B. and Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {gamma-Aminobutyric Acid;Cell Differentiation;Animals;Lysine;In Vitro;21 Epilepsy;Patch-Clamp Techniques;Epilepsy;Axons;Hippocampus;Pyramidal Cells;Biological Clocks;Macaca fascicularis;Dendrites;Receptors, GABA-A;Nerve Net;21 Neurophysiology;Neurons;Membrane Potentials;GABA Antagonists;Interneurons;24 Pubmed search results 2008}, Medline = {21602237}, Month = {12}, Nlm_Id = {8102140}, Number = {24}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e/Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM) U29, Luminy, 13273 Marseille, France. khazipov\@inmed.univ-mrs.fr}, Pages = {9770-81}, Pii = {21/24/9770}, Pubmed = {11739585}, Title = {Early development of neuronal activity in the primate hippocampus in utero}, Uuid = {DC4FA291-4B50-472B-A304-26CBA2171E5E}, Volume = {21}, Year = {2001}} @article{Khazipov:2004a, Abstract = {Sensorimotor coordination emerges early in development. The maturation period is characterized by the establishment of somatotopic cortical maps, the emergence of long-range cortical connections, heightened experience-dependent plasticity and spontaneous uncoordinated skeletal movement. How these various processes cooperate to allow the somatosensory system to form a three-dimensional representation of the body is not known. In the visual system, interactions between spontaneous network patterns and afferent activity have been suggested to be vital for normal development. Although several intrinsic cortical patterns of correlated neuronal activity have been described in developing somatosensory cortex in vitro, the in vivo patterns in the critical developmental period and the influence of physiological sensory inputs on these patterns remain unknown. We report here that in the intact somatosensory cortex of the newborn rat in vivo, spatially confined spindle bursts represent the first and only organized network pattern. The localized spindles are selectively triggered in a somatotopic manner by spontaneous muscle twitches, motor patterns analogous to human fetal movements. We suggest that the interaction between movement-triggered sensory feedback signals and self-organized spindle oscillations shapes the formation of cortical connections required for sensorimotor coordination.}, Author = {Khazipov, Rustem and Sirota, Anton and Leinekugel, Xavier and Holmes, Gregory L. and Ben-Ari, Yehezkel and Buzs{\'a}ki, Gy{\"o}rgy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 03:04:28 +0000}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Excitatory Postsynaptic Potentials;Motor Activity;Movement;Animals;Synapses;Aging;Rats;21 Epilepsy;Patch-Clamp Techniques;Spinal Cord;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Receptors, GABA-A;21 Neurophysiology;Somatosensory Cortex;Psychomotor Performance;24 Pubmed search results 2008;21 Cortical oscillations;Research Support, Non-U.S. Gov't; currOpinRvw}, Month = {12}, Nlm_Id = {0410462}, Number = {7018}, Organization = {INMED, INSERM U29, Avenue de Luminy, B.P. 13, 13273 Marseille, France.}, Pages = {758-61}, Pii = {nature03132}, Pubmed = {15592414}, Title = {Early motor activity drives spindle bursts in the developing somatosensory cortex}, Uuid = {F04AEC6A-F8B5-4D85-A118-3147F58C3D1B}, Volume = {432}, Year = {2004}, url = {papers/Khazipov_Nature2004.pdf}, Bdsk-File-2 = {papers/Khazipov_Nature2004a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03132}} @article{Khazipov:2006, Abstract = {During prenatal and early postnatal development, the cerebral cortex exhibits synchronized oscillatory network activity that is believed to be essential for the generation of neuronal cortical circuits. The nature and functional role of these early activity patterns are of central interest in neuroscience. Much of the research is performed in rodents and in vitro, but how closely do these model systems relate to the human fetal brain? In this review, we compare observations in humans with in vivo and in vitro rodent data, focusing on particular oscillatory activity patterns that share many common features: delta brushes, spindle bursts and spindle-like oscillations. There is considerable evidence that the basic functional properties of immature cortical networks are conserved through mammalian evolution, making the neonatal rodent an excellent model for studying early cortical activity and associated plasticity during the developmental period corresponding to the human fetal stage. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).}, Author = {Khazipov, Rustem and Luhmann, Heiko J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Periodicity;21 Cortical oscillations;24 Pubmed search results 2008;21 Neurophysiology;research support, non-u.s. gov't ;Models, Neurological;21 Activity-development;Nerve Net;Animals;Humans;Cerebral Cortex;review;Neurons}, Month = {7}, Nlm_Id = {7808616}, Number = {7}, Organization = {INMED, INSERM U29, 163 route de Luminy, 13273 Marseille, France. khazipov\@inmed.univ-mrs.fr}, Pages = {414-8}, Pii = {S0166-2236(06)00095-6}, Pubmed = {16713634}, Title = {Early patterns of electrical activity in the developing cerebral cortex of humans and rodents}, Uuid = {ADFE47FE-6A3B-45E2-B5A5-8913AF640A47}, Volume = {29}, Year = {2006}, url = {papers/Khazipov_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.05.007}} @article{Khoury:2007, Abstract = {Microglia are the principal immune cells of the brain. In Alzheimer disease, these brain mononuclear phagocytes are recruited from the blood and accumulate in senile plaques. However, the role of microglia in Alzheimer disease has not been resolved. Microglia may be neuroprotective by phagocytosing amyloid-beta (Abeta), but their activation and the secretion of neurotoxins may also cause neurodegeneration. Ccr2 is a chemokine receptor expressed on microglia, which mediates the accumulation of mononuclear phagocytes at sites of inflammation. Here we show that Ccr2 deficiency accelerates early disease progression and markedly impairs microglial accumulation in a transgenic mouse model of Alzheimer disease (Tg2576). Alzheimer disease mice deficient in Ccr2 accumulated Abeta earlier and died prematurely, in a manner that correlated with Ccr2 gene dosage, indicating that absence of early microglial accumulation leads to decreased Abeta clearance and increased mortality. Thus, Ccr2-dependent microglial accumulation plays a protective role in the early stages of Alzheimer disease by promoting Abeta clearance.}, Author = {Khoury, and Toft, and Hickman, and Means, and Terada, and Geula, and Luster,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {9502015}, Organization = {[1] Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology. 149 13th Street, Charlestown, Massachusetts 02129, USA. [2] Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA.}, Pii = {nm1555}, Pubmed = {17351623}, Title = {Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease}, Uuid = {9DA797ED-567C-4700-B52F-FA58172B53FB}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm1555}} @article{Kida:1993, Abstract = {Perivascular cells in the rat brain are an immunophenotypically defined group of cells which can be identified by their expression of the ED2 antigen. The present study investigates the role of perivascular cells as scavengers in the perivascular spaces of the rat brain and the relationship of these cells to microglia, macrophages, pericytes and smooth muscle cells. Particulate matter (Indian ink) was injected selectively into the perivascular spaces of the left caudoputamen of 59 rats. Animals were killed by cardiac perfusion of formalin or glutaraldehyde 2 h-2 years after ink injection. Cerebral hemispheres were examined histologically and immunocytochemically using the ED2 antibody for perivascular cells, ED1 for microglia and macrophages and OX-6 directed against Ia antigen [major histocompatibility complex (MHC) class II]. ED2+ perivascular cells ingested Indian ink in the perivascular spaces and expressed MHC class II antigen. Reactive microglia and macrophages in the perivascular parenchyma expressed ED1, but no ED2+ cells were seen outside the perivascular spaces. Transmission electron microscopy distinguished perivascular cells, which ingested carbon particles, from pericytes, which did not. The results of this study suggest that perivascular cells remain distinct from pericytes, microglia and macrophages and that they play a major role as scavengers in the perivascular spaces of the rat brain. This role reflects the importance of perivascular spaces as drainage pathways for soluble and insoluble material from the brain.}, Author = {Kida, S. and Steart, P. V. and Zhang, E. T. and Weller, R. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Neuroglia;Research Support, Non-U.S. Gov't;Immunohistochemistry;Microscopy, Electron;Histocompatibility Antigens Class II;Subarachnoid Space;Rats, Wistar;Rats;11 Glia;Macrophages;Blood Vessels;Male;Animals;Brain}, Medline = {93331866}, Nlm_Id = {0412041}, Number = {6}, Organization = {Department of Neuropathology, Southampton University Medical School, UK.}, Pages = {646-52}, Pubmed = {8337943}, Title = {Perivascular cells act as scavengers in the cerebral perivascular spaces and remain distinct from pericytes, microglia and macrophages}, Uuid = {C91ADFE9-2E79-42ED-B856-AA615DEFBE13}, Volume = {85}, Year = {1993}} @article{Kida:1995, Abstract = {Perivascular cells (PVCs) form an immunophenotypically defined population that plays an important scavenging role in the perivascular fluid drainage pathways in the rat brain; such cells may also act as antigen-presenting cells. The present study tests the hypotheses that (a) PVCs in human brain are distinct from microglia and haematogenous macrophages, and (b) PVCs within astrocytic tumours and peritumoral oedematous brain tissue react in a similar way to PVCs in the rat brain. Paraffin sections of formalin-fixed tissue from 10 astrocytomas, 10 anaplastic astrocytomas, 10 glioblastoma multiforme, peritumoral oedematous brain and from normal human brain were examined immunocytochemically using antibodies HLA-DR beta-chain for MHC class II antigen, PGM1 and MAC 387 directed against macrophage components, MT1 for T lymphocytes and GFAP for astrocytes. No PVCs, microglia or macrophages were labelled by these techniques in paraffin sections of normal brain. Microglia, macrophages recently derived from haematogenous monocytes and PVCs were labelled by immunocytochemistry in all tumours but were more numerous in glioblastomas than in astrocytomas or anaplastic astrocytomas. Perivascular cells were distinguished by their perivascular position, their expression of MHC class II antigen and were labelled by PGM1 antibody but not by MAC 387 antibody. Microglia and monocyte/macrophages, remote from blood vessels, on the other hand, were strongly labelled by MAC 387, moderately by PGM1 and showed weak expression of MHC class II antigen. A similar pattern of staining was seen in peritumoral oedematous tissue. These findings suggest that PVCs form a defined population of resident cells in the human brain and that they are distinct from microglia, monocytes and macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Kida, S. and Ellison, D. W. and Steart, P. V. and Weller, R. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Animals;Humans;Up-Regulation;Rats;Middle Aged;Macrophages;Lymphocytes;Brain Edema;Microglia;Major Histocompatibility Complex;11 Glia;Brain Neoplasms;Paraffin Embedding;HLA-DR Antigens;Glioblastoma;Astrocytoma;Adult;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {95334156}, Month = {4}, Nlm_Id = {7609829}, Number = {2}, Organization = {Department of Pathology (Neuropathology), Southampton General Hospital, UK.}, Pages = {121-9}, Pubmed = {7609842}, Title = {Characterization of perivascular cells in astrocytic tumours and peritumoral oedematous brain}, Uuid = {23143A5F-78E4-4ECA-8698-6A4E8F3012BC}, Volume = {21}, Year = {1995}} @article{Kiefer:1995, Abstract = {Lesions to the nervous system are nearly universally accompanied by a glial response involving both microglia and astrocytes. The growth and immunoregulatory cytokine transforming growth factor-beta 1 (TGF-beta 1) has potent effects on glial cells in vitro and may play a role in regulating glial activation in vivo. Though present only at very low levels in the normal brain, TGF-beta 1 mRNA is strongly upregulated in a number of different experimental models suitable to study glial responses. Following axotomy of the facial nerve of the rat, about a three-fold increase of TGF-beta 1 mRNA in the regenerating nucleus was observed with a time-course closely matching that of glial activation. Putative activated microglial cells are the major cellular source as revealed by in-situ hybridization. TGF-beta 1 was also found to be upregulated around brain tumors, in the spinal cord in response to peripheral nerve inflammation and in the postischemic hippocampus. In all systems investigated, TGF-beta 1 mRNA could be localized predominantly to cells with the typical nuclear morphology of microglia. In the peripheral nervous system, nerve transection leads to a massive increase in TGF-beta mRNA expression both proximal and distal to the cut site. However, whereas TGF-beta 1 mRNA is restricted to the nerve stump in the proximal segment, expression is diffuse and widespread throughout the denervated distal segment where it was localized mainly to cells with macrophage morphology.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Kiefer, R. and Streit, W. J. and Toyka, K. V. and Kreutzberg, G. W. and Hartung, H. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0736-5748}, Journal = {Int J Dev Neurosci}, Keywords = {Nervous System Physiology;Cytokines;Rats;Human;Not relevant;11 Glia;review, tutorial;Transforming Growth Factor beta;Animals;Trauma, Nervous System;review}, Medline = {96035130}, Nlm_Id = {8401784}, Number = {3-4}, Organization = {Department of Neurology, University of W{\"u}rzburg, Germany.}, Pages = {331-9}, Pubmed = {7572285}, Title = {Transforming growth factor-beta 1: a lesion-associated cytokine of the nervous system}, Uuid = {52ABA8C7-8B7D-4540-B267-0C4C7F98B1AB}, Volume = {13}, Year = {1995}} @article{Kiefer:1994, Abstract = {Malignant gliomas are associated with a state of systemic immunosuppression which appears to be partially mediated by transforming growth factor beta (TGF-beta) secreted from glioma cells. In a recently described animal model of malignant glioma, massive activation of local microglial cells and formation of microglia-derived macrophages has been observed in the absence of detectable tumour regression. We have investigated the in situ expression of TGF-beta in rat glioma as a possible cause of ineffective tumour destruction. Two weeks following unilateral injection of glioma cells, large tumours were observed in the affected hemisphere. In situ hybridization for TGF-beta 1 mRNA revealed an intense signal over the entire tumour area. In the peritumoural area, at sites of glial activation, a lower signal was obtained over cellular profiles containing nuclei typical for microglia, as well as other unidentified cellular profiles. No signal was obtained over the contralateral unaffected hemisphere. Northern blot analysis revealed a strong expression of TGF-beta 1 mRNA in tumour tissue, a lesser signal in the peritumoural reactive brain tissue and virtually no signal in normal tissue. Our data indicate that the experimental rat glioma has the potential to secrete TGF-beta in vivo which might render the microglial infiltration ineffective. TGF-beta expressed by activated microglial cells themselves might further inhibit their tumoricidal potential, thus contributing further to unrestrained tumour growth.}, Author = {Kiefer, R. and Supler, M. L. and Toyka, K. V. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Animals;Rats;Transforming Growth Factor beta;Neoplasm Transplantation;Female;RNA, Neoplasm;Rats, Wistar;Not relevant;11 Glia;RNA Probes;Brain Neoplasms;RNA, Messenger;In Situ Hybridization;Support, Non-U.S. Gov't;Blotting, Northern;Neuroglia;Cell Transplantation;Glioma}, Medline = {94232536}, Month = {1}, Nlm_Id = {7600130}, Number = {2}, Organization = {Department of Neurology, University of W{\"u}rzburg, FRG.}, Pages = {161-4}, Pubmed = {8177493}, Title = {In situ detection of transforming growth factor-beta mRNA in experimental rat glioma and reactive glial cells}, Uuid = {0AC174DF-946A-48BF-81C9-E4237426B391}, Volume = {166}, Year = {1994}} @article{Kiel:2005, Abstract = {To improve our ability to identify hematopoietic stem cells (HSCs) and their localization in vivo, we compared the gene expression profiles of highly purified HSCs and non-self-renewing multipotent hematopoietic progenitors (MPPs). Cell surface receptors of the SLAM family, including CD150, CD244, and CD48, were differentially expressed among functionally distinct progenitors. HSCs were highly purified as CD150(+)CD244(-)CD48(-) cells while MPPs were CD244(+)CD150(-)CD48(-) and most restricted progenitors were CD48(+)CD244(+)CD150(-). The primitiveness of hematopoietic progenitors could thus be predicted based on the combination of SLAM family members they expressed. This is the first family of receptors whose combinatorial expression precisely distinguishes stem and progenitor cells. The ability to purify HSCs based on a simple combination of SLAM receptors allowed us to identify HSCs in tissue sections. Many HSCs were associated with sinusoidal endothelium in spleen and bone marrow, though some HSCs were associated with endosteum. HSCs thus occupy multiple niches, including sinusoidal endothelium in diverse tissues.}, Author = {Kiel, Mark J. and Yilmaz, Omer H. and Iwashita, Toshihide and Yilmaz, Osman H. and Terhorst, Cox and Morrison, Sean J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {0413066}, Number = {7}, Organization = {Howard Hughes Medical Institute andDepartments of Internal Medicine and Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan, 48109.}, Pages = {1109-21}, Pii = {S0092-8674(05)00540-4}, Pubmed = {15989959}, Title = {SLAM Family Receptors Distinguish Hematopoietic Stem and Progenitor Cells and Reveal Endothelial Niches for Stem Cells}, Uuid = {72AB4025-E7C8-4155-AE2B-D493724F7BC2}, Volume = {121}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.05.026}} @article{Kiel:2007, Abstract = {Stem cells are proposed to segregate chromosomes asymmetrically during self-renewing divisions so that older ('immortal') DNA strands are retained in daughter stem cells whereas newly synthesized strands segregate to differentiating cells. Stem cells are also proposed to retain DNA labels, such as 5-bromo-2-deoxyuridine (BrdU), either because they segregate chromosomes asymmetrically or because they divide slowly. However, the purity of stem cells among BrdU-label-retaining cells has not been documented in any tissue, and the 'immortal strand hypothesis' has not been tested in a system with definitive stem cell markers. Here we tested these hypotheses in haematopoietic stem cells (HSCs), which can be highly purified using well characterized markers. We administered BrdU to newborn mice, mice treated with cyclophosphamide and granulocyte colony-stimulating factor, and normal adult mice for 4 to 10 days, followed by 70 days without BrdU. In each case, less than 6\%of HSCs retained BrdU and less than 0.5\%of all BrdU-retaining haematopoietic cells were HSCs, revealing that BrdU has poor specificity and poor sensitivity as an HSC marker. Sequential administration of 5-chloro-2-deoxyuridine and 5-iodo-2-deoxyuridine indicated that all HSCs segregate their chromosomes randomly. Division of individual HSCs in culture revealed no asymmetric segregation of the label. Thus, HSCs cannot be identified on the basis of BrdU-label retention and do not retain older DNA strands during division, indicating that these are not general properties of stem cells.}, Author = {Kiel, Mark J. and He, Shenghui and Ashkenazi, Rina and Gentry, Sara N. and Teta, Monica and Kushner, Jake A. and Jackson, Trachette L. and Morrison, Sean J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Animals;Cells, Cultured;Aging;Cyclophosphamide;Chromosome Segregation;Granulocyte Colony-Stimulating Factor;research support, non-u.s. gov't;08 Aberrant cell cycle;Time Factors;Bone Marrow Cells;Animals, Newborn;research support, n.i.h., extramural;Hematopoietic Stem Cells;Mice;24 Pubmed search results 2008;Bromodeoxyuridine;research support, u.s. gov't, non-p.h.s.;Stochastic Processes}, Month = {9}, Nlm_Id = {0410462}, Number = {7159}, Organization = {Howard Hughes Medical Institute, Life Sciences Institute, Department of Internal Medicine, and Centre for Stem Cell Biology, University of Michigan, Ann Arbor, Michigan 48109-2216, USA.}, Pages = {238-42}, Pii = {nature06115}, Pubmed = {17728714}, Title = {Haematopoietic stem cells do not asymmetrically segregate chromosomes or retain BrdU}, Uuid = {6B754168-7C58-4CA8-AC8D-5889E376307E}, Volume = {449}, Year = {2007}, url = {papers/Kiel_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06115}} @article{Kihara:2008, Abstract = {Gap junction (GJ) channels couple adjacent cells, allowing transfer of second messengers, ions, and molecules up to 1 kDa. These channels are composed by a multigene family of integral membrane proteins called connexins (Cx). In the retina, besides being essential circuit element in the visual processing, GJ channels also play important roles during its development. Herein, we analyzed Cx43, Cx45, Cx50, and Cx56 expression during chick retinal histogenesis. Cx exhibited distinct expression profiles during retinal development, except for Cx56, whose expression was not detected. Cx43 immunolabeling was observed at early development, in the transition of ventricular zone and pigmented epithelium. Later, Cx43 was seen in the outer plexiform and ganglion cell layers, and afterwards also in the inner plexiform layer. We observed remarkable changes in the phosphorylation status of this protein, which indicated modifications in functional properties of this Cx during retinal histogenesis. By contrast, Cx45 showed stable gene expression levels throughout development and ubiquitous immunoreactivity in progenitor cells. From later embryonic development, Cx45 was mainly observed in the inner retina, and it was expressed by glial cells and neurons. In turn, Cx50 was virtually absent in the chick retina at initial embryonic phases. Combination of PCR, immunohistochemistry and Western blot indicated that this Cx was present in differentiated cells, arising in parallel with the formation of the visual circuitry. Characterization of Cx expression in the developing chick retina indicated particular roles for these proteins and revealed similarities and differences when compared to other species. (c) 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008.}, Author = {Kihara, A. H. and Paschon, V. and Akamine, P. S. and Saito, K. C. and Leonelli, M. and Jiang, J. X. and Hamassaki, D. E. and Britto, L. R. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1932-8451}, Journal = {Dev Neurobiol}, Keywords = {24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {101300215}, Number = {11}, Organization = {Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S\~{a}o Paulo, S\~{a}o Paulo, S\~{a}o Paulo, Brazil.}, Pages = {1287-302}, Pubmed = {18506822}, Title = {Differential expression of connexins during histogenesis of the chick retina}, Uuid = {9369A1C6-9E68-4554-B416-B6EBE7482308}, Volume = {68}, Year = {2008}, url = {papers/Kihara_DevNeurobiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/dneu.20652}} @article{Kilb:2003, Abstract = {In mature cortex, activation of the cholinergic system induces oscillatory network activity and facilitates synaptic plasticity. We used an in vitro preparation of the intact cerebral cortex and cortical slices of the neonatal rat to study carbachol (CCh, >or=30 micro M)-induced network oscillations during the early postnatal period. Multi-site extracellular recordings revealed CCh-induced transient beta oscillations with an average duration of 4.6 +/- 0.2 s, amplitude of 123 +/- 7.4 microV and frequency of 17.7 +/- 0.5 Hz. These oscillations propagated uniformly at 0.5-1.5 mm/s over the cortex and were reversibly blocked by tetrodotoxin (TTX) and atropine, indicating that they depended on action potentials and activation of muscarinic receptors. The activity was not blocked by bicuculline methiodide or gabazine, but was reversibly abolished by kynurenic acid, indicating that activation of glutamate receptors, but not GABA-A receptors, was required. CNQX caused a significant decrease in the power of the Fourier frequency spectrum of the CCh-induced oscillations and CPP or MK-801 completely blocked the activity, indicating a contribution of AMPA/kainate receptors and an essential role of NMDA receptors. Oscillations were synchronized between sites separated horizontally by approximately 1 mm and for delays of 2-8 ms. Synchronized activity between neighboring recording sites was very stable over repeated applications of CCh. Whole-cell recordings from morphologically identified pyramidal neurons in the intact cortex revealed a close temporal correlation between CCh-induced membrane oscillations and local field potential recordings. In contrast, CCh-induced oscillations recorded in coronal neocortical slices were smaller in amplitude and frequency, suggesting that a widespread network of intracortical axonal connections is required for their generation.}, Author = {Kilb, Werner and Luhmann, Heiko J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Biological Clocks;21 Neurophysiology;Rats;research support, non-u.s. gov't ;in vitro ;Cholinergic Fibers;Rats, Wistar;Animals, Newborn;Nerve Net;Animals;Carbachol;24 Pubmed search results 2008;Cerebral Cortex;21 Cortical oscillations}, Month = {4}, Nlm_Id = {9110718}, Number = {4}, Organization = {Institute of Physiology and Pathophysiology, University of Mainz, Germany.}, Pages = {409-21}, Pubmed = {12631570}, Title = {Carbachol-induced network oscillations in the intact cerebral cortex of the newborn rat}, Uuid = {67366E36-1736-45AB-9D3E-868E1DFDA3A1}, Volume = {13}, Year = {2003}} @article{Kim:2000, Abstract = {The olfactory bulb glomerulus is a discrete and heterogeneous neuropil where olfactory receptor cell axons synapse with dendrites of mitral, tufted, and periglomerular neurons. To understand better the maturation of glomeruli and the spatiotemporal interactions that occur during postnatal development, we employed confocal microscopy and markers for immature and mature olfactory receptor cell axons in parallel with a marker for synaptic structure in maturing glomeruli. Sprague-Dawley rats at postnatal days 1, 6, 12, and 18 were processed for single- and double-label immunocytochemistry for olfactory marker protein (OMP), growth-associated protein (GAP-43), and synaptophysin. Mature or adult- like subcompartmental organization within the glomerulus emerged by postnatal day 12. Earlier in development immature axons entered the core of the glomerulus and moved to the periphery as they matured. However, beginning around 12 days postnatal, immature axons distributed in the periphery and moved toward the core as they matured. This change in the trajectories of axons into glomeruli suggests that different rules may be followed in establishing versus maintaining glomeruli. Double labeling with OMP and synaptophysin demonstrated strong colocalization compared with GAP-43 and synaptophysin, which showed much less colocalization, consistent with the notion that OMP is associated with more mature axons.}, Author = {Kim, H. and Greer, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:50 -0400}, Journal = {J Comp Neurol}, Keywords = {Nerve Tissue Proteins/metabolism;Synaptophysin/metabolism;Rats, Sprague-Dawley;Presynaptic Terminals/*metabolism/*ultrastructure;Rats;Immunohistochemistry;Olfactory Receptor Neurons/*cytology/*growth &development/metabolism;I pdf;Animal;Animals, Newborn;Olfactory Bulb/*cytology/*growth &development/metabolism;Support, U.S. Gov't, P.H.S.;Age Factors;Brain Mapping;GAP-43 Protein/metabolism;13 Olfactory bulb anatomy}, Number = {2}, Organization = {Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.}, Pages = {297-311.}, Title = {The emergence of compartmental organization in olfactory bulb glomeruli during postnatal development}, Uuid = {1BE95B64-FBFC-4D32-A9D6-52CDC9E99A65}, Volume = {422}, Year = {2000}, url = {papers/Kim_JCompNeurol2000.pdf}} @article{Kim:2000a, Abstract = {Inflammation in the brain has been increasingly associated with the development of a number of neurological diseases. The hallmark of neuroinflammation is the activation of microglia, the resident brain immune cells. Injection of bacterial endotoxin lipopolysaccharide (LPS) into the hippocampus, cortex, or substantia nigra of adult rats produced neurodegeneration only in the substantia nigra. Although LPS appeared to impact upon mesencephalic neurons in general, an extensive loss of dopaminergic neurons was observed. Analysis of the abundance of microglia revealed that the substantia nigra had the highest density of microglia. When mixed neuron-glia cultures derived from the rat hippocampus, cortex, or mesencephalon were treated with LPS, mesencephalic cultures became sensitive to LPS at a concentration as low as 10 ng/ml and responded in a dose-dependent manner with the production of inflammatory factors and a loss of dopaminergic and other neurons. In contrast, hippocampal or cortical cultures remained insensitive to LPS treatment at concentrations as high as 10 microg/ml. Consistent with in vivo observations, mesencephalic cultures had fourfold to eightfold more microglia than cultures from other regions. The positive correlation between abundance of microglia and sensitivity to LPS-induced neurotoxicity was further supported by the observation that supplementation with enriched microglia derived from mesencephalon or cortex rendered LPS-insensitive cortical neuron-glia cultures sensitive to LPS-induced neurotoxicity. These data indicate that the region-specific differential susceptibility of neurons to LPS is attributable to differences in the number of microglia present within the system and may reflect levels of inflammation-related factors produced by these cells.}, Author = {Kim, W. G. and Mohney, R. P. and Wilson, B. and Jeohn, G. H. and Liu, B. and Hong, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Cell Survival;Pregnancy;Tumor Necrosis Factor;Nerve Degeneration;Neurotoxins;Animals;Cells, Cultured;Rats;Brain;Microglia;Female;Cell Count;Lipopolysaccharides;Hippocampus;Substantia Nigra;11 Glia;Male;Alpha;Rats, Inbred F344;Cerebral Cortex;Neurons;Inflammation;Nitric Oxide}, Medline = {20394118}, Month = {8}, Nlm_Id = {8102140}, Number = {16}, Organization = {Neuropharmacology Section, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.}, Pages = {6309-16}, Pii = {20/16/6309}, Pubmed = {10934283}, Title = {Regional difference in susceptibility to lipopolysaccharide-induced neurotoxicity in the rat brain: role of microglia}, Uuid = {9857E136-E13A-11DA-9DD9-000D9346EC2A}, Volume = {20}, Year = {2000}, url = {papers/Kim_JNeurosci2000.pdf}} @article{Kim:2005, Abstract = {RNA interference (RNAi) is the process of sequence-specific post-transcriptional gene silencing triggered by double-stranded RNAs. In attempts to identify RNAi triggers that effectively function at lower concentrations, we found that synthetic RNA duplexes 25-30 nucleotides in length can be up to 100-fold more potent than corresponding conventional 21-mer small interfering RNAs (siRNAs). Some sites that are refractory to silencing by 21-mer siRNAs can be effectively targeted by 27-mer duplexes, with silencing lasting up to 10 d. Notably, the 27-mers do not induce interferon or activate protein kinase R (PKR). The enhanced potency of the longer duplexes is attributed to the fact that they are substrates of the Dicer endonuclease, directly linking the production of siRNAs to incorporation in the RNA-induced silencing complex. These results provide an alternative strategy for eliciting RNAi-mediated target cleavage using low concentrations of synthetic RNA as substrates for cellular Dicer-mediated cleavage.}, Author = {Kim, Dong-Ho H. and Behlke, Mark A. and Rose, Scott D. and Chang, Mi-Sook S. and Choi, Sangdun and Rossi, John J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {23 RNAi;23 Technique}, Month = {2}, Nlm_Id = {9604648}, Number = {2}, Organization = {Division of Molecular Biology, Beckman Research Institute of the City of Hope, 1450 East Duarte Rd., Duarte, California 91010, USA.}, Pages = {222-6}, Pii = {nbt1051}, Pubmed = {15619617}, Title = {Synthetic dsRNA Dicer substrates enhance RNAi potency and efficacy}, Uuid = {A5A5822B-C605-4375-92D8-A67367AECD24}, Volume = {23}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt1051}} @article{Kim:1991, Abstract = {Susceptibility of rodent cells to infection by ecotropic murine leukaemia viruses (MuLV) is determined by binding of the virus envelope to a membrane receptor that has multiple membrane-spanning domains. Cells infected by ecotropic MuLV synthesize envelope protein, gp70, which binds to this receptor, thereby preventing additional infections. The consequences of envelope-MuLV receptor binding for the infected host cell have not been directly determined, partly because the cellular function of the MuLV receptor protein is unknown. Here we report a coincidence in the positions of the first eight putative membrane-spanning domains found in the virus receptor and in two related proteins, the arginine and histidine permeases of Saccharomyces cerevisiae (Fig. 1), but not in any other proteins identified by computer-based sequence comparison of the GenBank data base. Xenopus oocytes injected with receptor-encoding messenger RNA show increased uptake of L-arginine, L-lysine and L-ornithine. The transport properties and the expression pattern of the virus receptor behave in ways previously attributed to y+, the principal transporter of cationic L-amino acids in mammalian cells.}, Author = {Kim, J. W. and Closs, E. I. and Albritton, L. M. and Cunningham, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Arginine;Histidine;Animals;In Vitro;Cations;Biological Transport;Recombinant Proteins;Oocytes;15 Retrovirus mechanism;Hydrogen-Ion Concentration;RNA, Messenger;Leukemia Virus, Murine;Xenopus laevis;Research Support, U.S. Gov't, P.H.S.;Blotting, Northern;Membrane Glycoproteins;Receptors, Virus;Mice;Membrane Transport Proteins;24 Pubmed search results 2008;Membrane Proteins;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {91343001}, Month = {8}, Nlm_Id = {0410462}, Number = {6337}, Organization = {Howard Hughes Medical Institute, Boston, Massachusetts.}, Pages = {725-8}, Pubmed = {1652100}, Title = {Transport of cationic amino acids by the mouse ecotropic retrovirus receptor}, Uuid = {068EAED3-EE2C-11DA-8605-000D9346EC2A}, Volume = {352}, Year = {1991}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/352725a0}} @article{Kinoshita:2002, Abstract = {Detailed knowledge of neuronal connectivity patterns is indispensable for studies of various aspects of brain functions. We previously established a genetic strategy for visualization of multisynaptic neural pathways by expressing wheat germ agglutinin (WGA) transgene under the control of neuron type-specific promoter elements in transgenic mice and DROSOPHILA: In this paper, we have developed a WGA- expressing recombinant adenoviral vector system and applied it for analysis of the olfactory system. When the WGA-expressing adenovirus was infused into a mouse nostril, various types of cells throughout the olfactory epithelium were infected and expressed WGA protein robustly. WGA transgene products in the olfactory sensory neurons were anterogradely transported along their axons to the olfactory bulb and transsynaptically transferred in glomeruli to dendrites of the second- order neurons, mitral and tufted cells. WGA protein was further conveyed via the lateral olfactory tract to the olfactory cortical areas including the anterior olfactory nucleus, olfactory tubercle, piriform cortex and lateral entorhinal cortex. In addition, transsynaptic retrograde labeling was observed in cholinergic neurons in the horizontal limb of diagonal band, serotonergic neurons in the median raphe nucleus, and noradrenergic neurons in the locus coeruleus, all of which project centrifugal fibers to the olfactory bulb. Thus, the WGA-expressing adenovirus is a useful and powerful tool for tracing neural pathways and could be used in animals that are not amenable to the transgenic technology.}, Author = {Kinoshita, N. and Mizuno, T. and Yoshihara, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:50 -0400}, Journal = {Chem Senses}, Keywords = {T pdf;23 Technique}, Number = {3}, Organization = {Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan. Department of Biochemistry, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.}, Pages = {215-23.}, Title = {Adenovirus-mediated WGA Gene Delivery for Transsynaptic Labeling of Mouse Olfactory Pathways}, Uuid = {4ECD2CD9-2385-4168-995B-DB6D8BA805DF}, Volume = {27}, Year = {2002}, url = {papers/Kinoshita_ChemSenses2002.pdf}} @article{Kintner:2002, Author = {Kintner, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {J Neurosci}, Keywords = {Neuroglia/cytology/physiology;Nerve Tissue Proteins/metabolism;01 Adult neurogenesis general;Body Patterning/physiology;Spinal Cord/cytology/embryology/metabolism;Helix-Loop-Helix Motifs;Neurons/*cytology/physiology;Stem Cells/*cytology/physiology;Human;Aging/physiology;A both;Cell Lineage/physiology;Animal;Central Nervous System/*cytology/*embryology/metabolism;Cell Differentiation/physiology;Vertebrates}, Number = {3}, Organization = {The Salk Institute for Biological Studies, San Diego, California 92186, USA. kintner\@salk.edu}, Pages = {639-43.}, Title = {Neurogenesis in embryos and in adult neural stem cells}, Uuid = {9834F0AD-4004-4214-BBE9-8E7390087F92}, Volume = {22}, Year = {2002}, url = {papers/Kintner_JNeurosci2002.pdf}} @article{Kiper:1999, Abstract = {In recent years, the analysis of the coherence between signals recorded from the scalp [electroencephalographic (EEG) coherence] has been used to assess the functional properties of cortico-cortical connections, both in animal models and in humans. However, the experimental validation of this technique is still scarce. Therefore we applied it to the study of the callosal connections between the visual areas of the two hemispheres, because this particular set of cortico-cortical connections can be activated in a selective way by visual stimuli. Indeed, in primary and in low-order secondary visual areas, callosal axons interconnect selectively regions, which represent a narrow portion of the visual field straddling the vertical meridian and, within these regions, neurons that prefer the same stimulus orientation. Thus only isooriented stimuli located near the vertical meridian are expected to change interhemispheric coherence by activating callosal connections. Finally, if such changes are found and are indeed mediated by callosal connections, they should disappear after transection of the corpus callosum. We perfomed experiments on seven paralyzed and anesthetized ferrets, recording their cortical activity with epidural electrodes on areas 17/18, 19, and lateral suprasylvian, during different forms of visual stimulation. As expected, we found that bilateral iso-oriented stimuli near the vertical meridian, or extending across it, caused a significant increase in interhemispheric coherence in the EEG beta-gamma band. Stimuli with different orientations, stimuli located far from the vertical meridian, as well as unilateral stimuli failed to affect interhemispheric EEG coherence. The stimulus-induced increase in coherence disappeared after surgical transection of the corpus callosum. The results suggest that the activation of cortico-cortical connections can indeed be revealed as a change in EEG coherence. The latter can therefore be validly used to investigate the functionality of cortico-cortical connections.}, Author = {Kiper, D. C. and Knyazeva, M. G. and Tettoni, L. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Visual Cortex;Laterality;Photic Stimulation;Electroencephalography;Female;Not relevant;Ferrets;11 Glia;Animals;Support, Non-U.S. Gov't;Visual Pathways;Corpus Callosum}, Medline = {20070013}, Month = {12}, Nlm_Id = {0375404}, Number = {6}, Organization = {Institut de Biologie Cellulaire et de Morphologie, Universit{\'e} de Lausanne, 1005 Lausanne, Switzerland.}, Pages = {3082-94}, Pubmed = {10601443}, Title = {Visual stimulus-dependent changes in interhemispheric EEG coherence in ferrets}, Uuid = {BB12EC0C-78AA-4601-895F-A33EA791774F}, Volume = {82}, Year = {1999}} @article{Kiper:2002, Abstract = {We analyzed the visual functions of two patients (MS, FJ) with bilateral lesion of the primary visual cortex, which occurred at gestational age 33 wk in MS and at postnatal month 7 in FJ. In both patients basic visual functions--visual acuity, contrast sensitivity, color, form, motion perception-are similarly preserved or modestly impaired. Functions requiring higher visual processing, particularly figure-ground segregation based on textural cues, are severely impaired. In MS, studied longitudinally, the deficits attenuated between the ages of 4.5 and 8 y, suggesting that the developing visual system can display a considerable degree of adaptive plasticity several years after the occurrence of a lesion. In FJ (age 18:9 to 20:6 y), who is more impaired, the recovery, if any, was less.}, Author = {Kiper, D. C. and Zesiger, P. and Maeder, P. and Deonna, T. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Journal = {Neural Plast}, Keywords = {Adolescent;Human;Psychophysics;Form Perception;Recovery of Function;Neuronal Plasticity;Age of Onset;Female;Child;Not relevant;11 Glia;Male;Visual Fields;Vision;Support, Non-U.S. Gov't;Visual Acuity;Visual Cortex;Agnosia;Longitudinal Studies;Neuropsychological Tests}, Medline = {22346599}, Nlm_Id = {100883417}, Number = {1}, Organization = {Institut de Biologie Cellulaire et de Morphologie, University of Lausanne, Switzerland.}, Pages = {1-25}, Pubmed = {12458786}, Title = {Vision after early-onset lesions of the occipital cortex: I. Neuropsychological and psychophysical studies}, Uuid = {88FA4CE8-EC51-4417-9CEC-521624B2EE88}, Volume = {9}, Year = {2002}} @article{Kippin:2004, Abstract = {Many of the effects of prenatal stress on the endocrine function, brain morphology, and behavior in mammals can be reversed by brief sessions of postnatal separation and handling. We have tested the hypothesis that the effects of both the prenatal and postnatal experiences are mediated by negative and positive regulation of neural stem cell (NSC) number during critical stages in neurodevelopment. We used the in vitro clonal neurosphere assay to quantify NSCs in hamsters that had experienced prenatal stress (maternal restraint stress for 2 hr per day, for the last 7 d of gestation), postnatal handling (maternal-offspring separation for 15 min per day during postnatal days 1-21), orboth. Prenatal stress reduced the number of NSCs derived from the subependyma of the lateral ventricle. The effect was already present at postnatal day 1 and persisted into adulthood (at least 14 months of age). Similarly, prenatal stress reduced in vivo proliferation in the adult subependyma of the lateral ventricle. Conversely, postnatal handling increased NSC number and reversed the effect of prenatal stress. The effects of prenatal stress on NSCs and proliferation and the effect of postnatal handling on NSCs did not differ between male and females. The findings demonstrate that environmental factors can produce changes in NSC number that are present at birth and endure into late adulthood. These changes may underlie some of the behavioral effects produced by prenatal stress and postnatal handling. 1529-2401 Journal Article}, Author = {Kippin, T. E. and Cain, S. W. and Masum, Z. and Ralph, M. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {J Neurosci}, Keywords = {C pdf;04 Adult neurogenesis factors}, Number = {11}, Organization = {Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. tod.kippin\@utoronto.ca}, Pages = {2832-6}, Title = {Neural stem cells show bidirectional experience-dependent plasticity in the perinatal mammalian brain}, Uuid = {64E39CC1-16F9-4642-ACEE-88FB9F0740CF}, Volume = {24}, Year = {2004}, url = {papers/Kippin_JNeurosci2004.pdf}} @article{Kirichok:2006, Abstract = {In mammals, sperm cells become motile during ejaculation and swim up the female reproductive tract. Before fertilization and to overcome various barriers, their motility must be hyperactivated, a motion that is characterized by vigorous asymmetric tail beating. Hyperactivation requires an increase in calcium in the flagella, a process that probably involves plasmalemmal ion channels. Numerous attempts in the past two decades to understand sperm cell channels have been frustrated by the difficulty of measuring spermatozoan transmembrane ion currents. Here, by using a simple approach to patch-clamp spermatozoa and to characterize whole-spermatozoan currents, we describe a constitutively active flagellar calcium channel that is strongly potentiated by intracellular alkalinization. This current is not present in spermatozoa lacking the sperm-specific putative ion channel protein, CatSper1. This plasma membrane protein of the six transmembrane-spanning ion channel superfamily is specifically localized to the principal piece of the sperm tail and is required for sperm cell hyperactivation and male fertility. Our results identify CatSper1 as a component of the key flagellar calcium channel, and suggest that intracellular alkalinization potentiates CatSper current to increase intraflagellar calcium and induce sperm hyperactivation.}, Author = {Kirichok, Yuriy and Navarro, Betsy and Clapham, David E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Organ Specificity;Ion Channel Gating;Electric Conductivity;Male;Patch-Clamp Techniques;21 Neurophysiology;24 Pubmed search results 2008;Alkalies;Calcium Channels;Spermatozoa;Calcium;Substrate Specificity;Animals;Ion Transport;Sperm Tail;Mice;Hydrogen-Ion Concentration}, Month = {2}, Nlm_Id = {0410462}, Number = {7077}, Organization = {Howard Hughes Medical Institute, Department of Cardiology, Children's Hospital and Harvard Medical School Enders 1309, Boston, Massachusetts 02115, USA.}, Pages = {737-40}, Pii = {nature04417}, Pubmed = {16467839}, Title = {Whole-cell patch-clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel}, Uuid = {0E16FF32-351B-4F6E-B06D-CB779D984702}, Volume = {439}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04417}} @article{Kirn:1999, Abstract = {Projection neurons are added to the high vocal center (HVC) of adult songbirds. Here we report on events associated with their initial arrival in HVC. Neurons formed in adult canaries were labeled with [(3)H]-thymidine and examined 8, 15, 22, and 31 days later. By 8 days, some [(3)H]-labeled cells with the nuclear profile of postmigratory neurons were already present in HVC but could not be retrogradely labeled by Fluoro-Gold injections in the robust nucleus of the archistriatum (RA); 7 days later, a few such cells could be backfilled from RA. Thus, new neurons may arrive in HVC as much as 1 week prior to establishing connections with RA. By 31 days, 43\%of the [(3)H]-labeled neurons could be backfilled from RA. In no case were new neurons backfilled by tracer injections into Area X, suggesting that newly formed HVC cells do not establish a transient connection with this region. At all survival times, the somata of new neurons were often clustered tightly together with other HVC neurons that differed in age and projection. Between days 15 and 25 after their birth, half of the new HVC neurons disappeared. We conclude: (1) that neurons arrive in HVC earlier than previously thought, (2) that soon after their arrival they become part of cell clusters in HVC, and (3) that in addition to the previously described death of new neurons that occurs over a period of months, there is an early wave of death that occurs soon after new neurons adopt a postmigratory phenotype.}, Author = {Kirn, J. R. and Fishman, Y. and Sasportas, K. and Alvarez-Buylla, A. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Comp Neurol}, Keywords = {01 Adult neurogenesis general;Fluorescent Dyes/diagnostic use;Canaries/*anatomy &histology/growth &development;Cerebral Ventricles/cytology;A abstr;Animal;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Male;Cell Movement;Telencephalon/*cytology/growth &development;Cell Lineage}, Number = {3}, Organization = {Biology Department, Wesleyan University, Middletown, Connecticut 06459- 0170, USA. jrkirn\@wesleyan.edu}, Pages = {487-94.}, Title = {Fate of new neurons in adult canary high vocal center during the first 30 days after their formation}, Uuid = {76F6D583-D85E-4F3D-8C5C-9C5D06DD8FC8}, Volume = {411}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10413781}} @article{Kirn:1991, Abstract = {Neurons are produced in the adult canary telencephalon. Many of these cells are incorporated into the high vocal center (nucleus HVC), which participates in the control of learned song. In the present work, 3H- thymidine and fluorogold were employed to follow the differentiation and survival of HVC neurons born in adulthood. We found that many HVC neurons born in September grow long axons to the robust nucleus of the archistriatum (nucleus RA) and thus become part of the efferent pathway for song control. Many of these new neurons have already established their connections with RA by 30 d after their birth. By 240 d, 75-80\%of the September-born HVC neurons project to RA. Most of these new projection neurons survive at least 8 months. The longevity of HVC neurons born in September suggests that these cells remain part of the vocal control circuit long enough to participate in the yearly renewal of the song repertoire.}, Author = {Kirn, J. R. and Alvarez-Buylla, A. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci}, Keywords = {Cell Survival;Cell Differentiation;Axons/physiology;Thymidine/metabolism;Neurons/cytology/*physiology;Animal;Brain/cytology/*physiology;Telencephalon/cytology/*physiology;DNA Replication;Male;01 Adult neurogenesis general;Learning;Support, U.S. Gov't, P.H.S.;Canaries/*physiology;Tritium;*Vocalization, Animal;Autoradiography;A abstr}, Number = {6}, Organization = {Rockefeller University Field Research Center, Millbrook, New York 12545.}, Pages = {1756-62.}, Title = {Production and survival of projection neurons in a forebrain vocal center of adult male canaries}, Uuid = {B7B2FBB3-655B-4AB3-BB47-055D74443A41}, Volume = {11}, Year = {1991}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2045885}} @article{Kirschenbaum:1994, Abstract = {It has traditionally been held that the adult brain is incapable of significant self-repair, due in part to its inability to generate new neurons. Nevertheless, rodents and birds have been found to harbor neural precursor cells in adulthood. We asked whether the adult human brain might retain such precursors, by culturing samples of temporal lobe under conditions permissive for neuronal differentiation, while exposed to 3H-thymidine. Adult human temporal lobe cultures, derived from cortex, subcortex, and periventricular subependymal zone (SZ), were incubated for 7-28 d, stained for neuronal and glial antigens, and autoradiographed. Neuron-like cells were found in explant outgrowths and monolayer dissociates of SZ and periventricular white matter, but not cortex; they expressed neuronal antigens including MAP-2, MAP-5, NF, and N-CAM, and were GFAP-. Neurons responded to K+ depolarization with rapid and reversible increases in intracellular Ca2+, with much greater increments than those noted in glia. Although most neurons were not 3H-thymidine labeled, a small number of MAP-2+ and MAP-5+/GFAP- cells did incorporate 3H-thymidine, suggesting neuronal production from precursor mitosis. Rare 3H-thymidine+ neurons were also found in cultures of subventricular white matter; in these, GFAP+ astrocytic mitogenesis was common, while O4+ oligodendrocytes, although the predominant cell type, were largely postmitotic. Thus, the adult human forebrain harbors precursor cells that retain the potential for neuronal production and differentiation in vitro. eng Journal Article}, Author = {Kirschenbaum, B. and Nedergaard, M. and Preuss, A. and Barami, K. and Fraser, R. A. and Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Journal = {Cereb Cortex}, Keywords = {Neurons/*physiology;Human;Cells, Cultured;Image Processing, Computer-Assisted;Thymidine/metabolism;Phenotype;Female;02 Adult neurogenesis migration;Calcium/metabolism;Male;BB abstr;03 Adult neurogenesis progenitor source;Middle Age;Support, Non-U.S. Gov't;Neuroglia/physiology;Adult;Support, U.S. Gov't, P.H.S.;Cell Differentiation/physiology;Immunohistochemistry;Autoradiography;Adolescence;Culture Media;Prosencephalon/cytology/*growth &development}, Number = {6}, Organization = {Department of Neurology, Cornell University Medical College, New York, New York 10021.}, Pages = {576-89.}, Title = {In vitro neuronal production and differentiation by precursor cells derived from the adult human forebrain}, Uuid = {D78D30D6-98C3-450D-8FCC-D90921194C05}, Volume = {4}, Year = {1994}} @article{Kirschenbaum:1999, Abstract = {Neurons continue to be born in the subventricular zone (SVZ) of the lateral ventricles of adult mice. These cells migrate as a network of chains through the SVZ and the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into mature neurons. The OB is the only known target for these neuronal precursors. Here, we show that, after elimination of the OB, the SVZ and RMS persist and become dramatically larger. The proportion of dividing [bromodeoxyuridine (BrdU)-labeled] or dying (pyknotic or terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end- labeled) cells in the RMS was not significantly affected at 3 d or 3 weeks after bulbectomy (OBX). However, by 3 months after OBX, the percentage of BrdU-labeled cells in the RMS decreased by half and that of dying cells doubled. Surprisingly, the rostral migration of precursors continued along the RMS after OBX. This was demonstrated by focal microinjections of BrdU and grafts of SVZ cells carrying LacZ under the control of a neuron-specific promoter gene. Results indicate that the OB is not essential for proliferation and the directional migration of SVZ precursors.}, Author = {Kirschenbaum, B. and Doetsch, F. and Lois, C. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Neurosci}, Keywords = {Cerebral Ventricles/*cytology;Neurons/*cytology/enzymology/*physiology;Olfactory Bulb/*physiology;Animal;02 Adult neurogenesis migration;Time Factors;Mice, Transgenic/genetics;Male;Stem Cells/*cytology/*physiology;Mice, Inbred Strains;Phosphopyruvate Hydratase/genetics/metabolism;Cell Division/physiology;B-9;Nerve Net/physiology;Cell Transplantation;Support, U.S. Gov't, P.H.S.;Mice;Cell Movement/physiology}, Number = {6}, Organization = {The Rockefeller University, New York, New York 10021, USA.}, Pages = {2171-80.}, Title = {Adult subventricular zone neuronal precursors continue to proliferate and migrate in the absence of the olfactory bulb}, Uuid = {0905D5EA-E218-4058-A12B-3A78647B6FF9}, Volume = {19}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10066270%20http://www.jneurosci.org/cgi/content/full/19/6/2171}} @article{Kirschenbaum:1995, Abstract = {Neuronal precursor cells persist in the adult forebrain ependymal/subependymal zone (SZ) and have been found to produce neurons in cultures derived from birds, rodents, and humans. We postulated that the survival of neurons generated from these cells might be constrained in adulthood by the local absence of trophic support. To test this hypothesis, we established explant cultures of adult rat forebrain SZ and assessed the effect of defined neurotrophins on the survival of new neurons arising from these explants. We found that microtubule-associated protein 2+ neurons arose from explants derived from a wide area of the SZ, spanning the rostral 6 mm of the ventricular system. In cultures exposed to brain-derived neurotrophic factor (BDNF), >35\%of new neurons survived at 22 days in vitro (DIV), and >25\%survived at 42 DIV, concurrent with the virtually complete loss of neurons in unsupplemented controls. The surviving cells expressed trkB, the high-affinity receptor for BDNF. In contrast, neither nerve growth factor nor neurotrophic factor 3 enhanced neuronal survival. Thus, BDNF supports the survival of neurons produced by the adult rat forebrain and may act as a permissive factor for neuronal recruitment in adulthood. 0027-8424 Journal Article}, Author = {Kirschenbaum, B. and Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Nerve Growth Factors/*pharmacology;Animals;Receptor, Ciliary Neurotrophic Factor;Rats;Thymidine/metabolism;Comparative Study;Brain-Derived Neurotrophic Factor;Neurotrophin 3;Rats, Sprague-Dawley;Kinetics;C abstr;Receptors, Nerve Growth Factor/analysis/biosynthesis;Analysis of Variance;Support, Non-U.S. Gov't;Nerve Tissue Proteins/*pharmacology;Prosencephalon/anatomy &histology/*cytology;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Tritium;Organ Culture;Neurons/*cytology/drug effects;Cell Division/drug effects}, Number = {1}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.}, Pages = {210-4}, Pubmed = {7816819}, Title = {Brain-derived neurotrophic factor promotes the survival of neurons arising from the adult rat forebrain subependymal zone}, Uuid = {F8404A44-8522-4A3D-A530-4E67950EE7D9}, Volume = {92}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7816819}} @article{Kishi:1990, Abstract = {In order to examine the relationship between radial glial fibers and the migrating bipolar subependymal cells which are considered to be post-mitotic precursors of granule cells in the rat olfactory bulb, the arrangement of radial glial fibers along the anterior lateral and olfactory ventricles was analysed by Golgi techniques, immunohistochemical demonstration of glial fibrillary acidic protein, and electron microscopy. In rats during their first 3 weeks of life, the bipolar subependymal cells migrate along the anterior lateral and olfactory ventricles into the center of the olfactory bulb, whereas the radial glial fibers radiating from the ventricular surface are arranged rather perpendicularly to the direction of migration of bipolar cells. Hence radial glial fibers in this region are not considered to act as guides for the rostralwards migration of subependymal cells.}, Author = {Kishi, K. and Peng, J. Y. and Kakuta, S. and Murakami, K. and Kuroda, M. and Yokota, S. and Hayakawa, S. and Kuge, T. and Asayama, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0914-9465}, Journal = {Arch Histol Cytol}, Keywords = {Ependyma;Glial Fibrillary Acidic Protein;Neuroglia;Immunohistochemistry;Microscopy, Electron;Rats;Stem Cells;Olfactory Bulb;Animals;Cell Movement;Rats, Inbred Strains;13 Olfactory bulb anatomy;Axons}, Medline = {90321712}, Month = {5}, Nlm_Id = {8806082}, Number = {2}, Organization = {Department of Anatomy, Toho University School of Medicine, Tokyo, Japan.}, Pages = {219-26}, Pubmed = {2372444}, Title = {Migration of bipolar subependymal cells, precursors of the granule cells of the rat olfactory bulb, with reference to the arrangement of the radial glial fibers}, Uuid = {FBEC0A0A-D067-11DA-8A8C-000D9346EC2A}, Volume = {53}, Year = {1990}} @article{Kishi:1987, Abstract = {The morphology and the development of the cells in the subependymal layer and of granule cells of the olfactory bulb were examined by Nissl and Golgi staining in postnatal rats. The subependymal layer around the anterior lateral ventricle extends into the center of the olfactory bulb. The mitotic indexes in the subependymal layer are high at the level of the anterior horn of the lateral ventricle and very low inside the olfactory bulb during the first 3 weeks after birth. Golgi-stained subependymal cells are classified into two main groups. One group consists of smoothly contoured bipolar cells with leading processes tipped by large growth cones and with trailing processes. They make up a majority of Golgi-stained subependymal cells during the first 3 weeks of age, and smaller numbers of them continue to exist at 37 and 60 days. They migrate with their growth cones oriented toward the olfactory bulb from the level of the anterior lateral ventricle into the granular layer of the olfactory bulb, where they differentiate into the definitive granule cells: their somata enlarge; the leading processes elongate, branch, sprout many gemmules, and become the peripheral processes; and the trailing processes become the basal dendrites. The other group contains relatively large cells with many cytoplasmic processes that are considered to belong to the glial cell line.}, Author = {Kishi, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Cell Differentiation;Neuroglia;Rats;Olfactory Bulb;Animals;Cell Movement;13 Olfactory bulb anatomy;Neurons}, Medline = {87195543}, Month = {4}, Nlm_Id = {0406041}, Number = {1}, Pages = {112-24}, Pubmed = {3571532}, Title = {Golgi studies on the development of granule cells of the rat olfactory bulb with reference to migration in the subependymal layer}, Uuid = {FBEC1551-D067-11DA-8A8C-000D9346EC2A}, Volume = {258}, Year = {1987}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902580109}} @article{Kitai:2000, Abstract = {Microglia are the major target of HIV-1 infection in the brain. Microglial infection is CD4-dependent, but the role of chemokine receptors CCR5 and CCR3 and their natural ligands in modulating HIV-1 infection in microglia has been questioned. In primary human fetal microglial cultures, we demonstrate that HIV-1 infection of these cells is dependent on CCR5, since an antibody to CCR5 completely blocked productive infection. Anti-CCR3, in contrast, had a smaller inhibitory effect which was not statistically significant. The chemokine ligands for CCR5, RANTES and MIP-1beta, also potently inhibited HIV-1 infection in microglia, but the third ligand MIP-1alpha failed to show inhibition. Interestingly, when microglial cultures were treated with antibodies specific to each of these chemokines, HIV-1 infection was enhanced by anti-RANTES and anti-MIP-1beta, but not by anti-MIP-1alpha. These results demonstrate the presence of endogenous chemokines that act as endogenous inhibitors of HIV-1 infection in microglia. Additionally, IFNbeta, a known anti-viral cytokine, also provided potent inhibition of viral infection as well as induction of all three chemokines in microglia. These results suggest the possibility that type I interferon can down-modulate microglial HIV-1 infection in vivo by multiple mechanisms.}, Author = {Kitai, R. and Zhao, M. L. and Zhang, N. and Hua, L. L. and Lee, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {AIDS Dementia Complex;Human;Antiviral Agents;HIV-1;Cells, Cultured;HIV Envelope Protein gp41;Humans;Brain;Microglia;Lipopolysaccharides;11 Glia;Giant Cells;Research Support, U.S. Gov't, P.H.S.;RANTES;Support, U.S. Gov't, P.H.S.;Receptors, CCR5;Macrophage Inflammatory Protein-1;Virus Replication;Interferon-beta;Neuroimmunomodulation}, Medline = {20481316}, Month = {10}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Pathology (Neuropathology), Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.}, Pages = {230-9}, Pii = {S0165572800003155}, Pubmed = {11024554}, Title = {Role of MIP-1beta and RANTES in HIV-1 infection of microglia: inhibition of infection and induction by IFNbeta}, Uuid = {87A71E2F-EF88-4E69-BB21-4D5C3C1B5D04}, Volume = {110}, Year = {2000}} @article{Kitamura:2003, Abstract = {Most of the human genome has now been sequenced and about 30,000 potential open reading frames have been identified, indicating that we use these 30,000 genes to functionally organize our biologic activities. However, functions of many genes are still unknown despite intensive efforts using bioinformatics as well as transgenic and knockout mice. Retrovirus-mediated gene transfer is a powerful tool that can be used to understand gene functions. We have developed a variety of retrovirus vectors and efficient packaging cell lines that have facilitated the development of efficient functional expression cloning methods. In this review, we describe retrovirus-mediated strategies used for investigation of gene functions and function-based screening strategies. 0301-472x Journal Article Review Review, Tutorial}, Author = {Kitamura, T. and Koshino, Y. and Shibata, F. and Oki, T. and Nakajima, H. and Nosaka, T. and Kumagai, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {Exp Hematol}, Keywords = {Retroviridae/*genetics;*Gene Transfer Techniques;Structure-Activity Relationship;Virus Assembly;*Genomics;Genetic Vectors/*genetics;Human;J, T, pdf;15 Retrovirus mechanism;Support, Non-U.S. Gov't;Animals;Cloning, Molecular;Protein Sorting Signals;Polymerase Chain Reaction}, Number = {11}, Organization = {Divisions of Cellular Therapy and Hematopoietic Factors, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. kitamura\@ims.u-tokyo.ac.jp}, Pages = {1007-14}, Title = {Retrovirus-mediated gene transfer and expression cloning: powerful tools in functional genomics}, Uuid = {926A223C-1429-42DB-B3CA-F38163B75A74}, Volume = {31}, Year = {2003}, url = {papers/Kitamura_ExpHematol2003.pdf}} @article{Kitamura:2002, Abstract = {Male embryonic mice with mutations in the X-linked aristaless-related homeobox gene (Arx) developed with small brains due to suppressed proliferation and regional deficiencies in the forebrain. These mice also showed aberrant migration and differentiation of interneurons containing gamma-aminobutyric acid (GABAergic interneurons) in the ganglionic eminence and neocortex as well as abnormal testicular differentiation. These characteristics recapitulate some of the clinical features of X-linked lissencephaly with abnormal genitalia (XLAG) in humans. We found multiple loss-of-function mutations in ARX in individuals affected with XLAG and in some female relatives, and conclude that mutation of ARX causes XLAG. The present report is, to our knowledge, the first to use phenotypic analysis of a knockout mouse to identify a gene associated with an X-linked human brain malformation.}, Author = {Kitamura, Kunio and Yanazawa, Masako and Sugiyama, Noriyuki and Miura, Hirohito and Iizuka-Kogo, Akiko and Kusaka, Masatomo and Omichi, Kayo and Suzuki, Rika and Kato-Fukui, Yuko and Kamiirisa, Kyoko and Matsuo, Mina and Kamijo, Shin-ichi and Kasahara, Megumi and Yoshioka, Hidefumi and Ogata, Tsutomu and Fukuda, Takayuki and Kondo, Ikuko and Kato, Mitsuhiro and Dobyns, William B. and Yokoyama, Minesuke and Morohashi, Ken-ichirou}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Cell Differentiation;Apoptosis;Genetic Vectors;Alleles;24 Pubmed search results 2008;Epithelial Cells;Immunohistochemistry;Genitalia;Male;Models, Genetic;10 Development;Animals;Brain;Linkage (Genetics);Testis;Base Sequence;Cell Movement;Phenotype;Homeodomain Proteins;X Chromosome;Transcription Factors;Transfection;Cell Division;Molecular Sequence Data;Bromodeoxyuridine;research support, u.s. gov't, p.h.s.;Mutation;comparative study;Amino Acid Sequence;Prosencephalon;Syndrome;DNA, Complementary;research support, non-u.s. gov't;Mice, Knockout;Mice;Neurons;Humans;Microscopy, Fluorescence;10 genetics malformation}, Month = {11}, Nlm_Id = {9216904}, Number = {3}, Organization = {Mitsubishi Kagaku Institute of Life Sciences, 11 Minamiooya, Machida, Tokyo 194-8511, Japan. kunio\@libra.ls.m-kagaku.co.jp}, Pages = {359-69}, Pii = {ng1009}, Pubmed = {12379852}, Title = {Mutation of ARX causes abnormal development of forebrain and testes in mice and X-linked lissencephaly with abnormal genitalia in humans}, Uuid = {4EA79F44-20F3-4D2D-99AE-DDC18EEF1381}, Volume = {32}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ng1009}} @article{Klausberger:2008, Abstract = {In the cerebral cortex, diverse types of neurons form intricate circuits and cooperate in time for the processing and storage of information. Recent advances reveal a spatiotemporal division of labor in cortical circuits, as exemplified in the CA1 hippocampal area. In particular, distinct GABAergic (gamma-aminobutyric acid-releasing) cell types subdivide the surface of pyramidal cells and act in discrete time windows, either on the same or on different subcellular compartments. They also interact with glutamatergic pyramidal cell inputs in a domain-specific manner and support synaptic temporal dynamics, network oscillations, selection of cell assemblies, and the implementation of brain states. The spatiotemporal specializations in cortical circuits reveal that cellular diversity and temporal dynamics coemerged during evolution, providing a basis for cognitive behavior.}, Author = {Klausberger, Thomas and Somogyi, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Neurons;Synapses;gamma-Aminobutyric Acid;Dendrites;24 Pubmed search results 2008;Hippocampus;Pyramidal Cells;Neural Pathways;Evolution;Interneurons;Cognition;Animals;Humans;Nerve Net;review;Axons}, Month = {7}, Nlm_Id = {0404511}, Number = {5885}, Organization = {MRC Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, UK. thomas.klausberger\@pharm.ox.ac.uk}, Pages = {53-7}, Pii = {321/5885/53}, Pubmed = {18599766}, Title = {Neuronal diversity and temporal dynamics: the unity of hippocampal circuit operations}, Uuid = {CD82C252-3398-4F19-B624-85C451B5FC98}, Volume = {321}, Year = {2008}, url = {papers/Klausberger_Science2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1149381}} @article{Klein:2001, Abstract = {Ephrins are cell surface associated ligands for Eph receptor tyrosine kinases and are implicated in repulsive axon guidance, cell migration, topographic mapping and angiogenesis. During the past year, Eph receptors have been shown to associate with glutamate receptors in excitatory neurons, suggesting a role in synapse formation or function. Moreover, ephrin/Eph signaling appears to regulate neural stem cell proliferation and migration in adult mouse brains. The mode of action of ephrin/Ephs has been expanded from repulsion to adhesion and from cell surface attachment to regulated cleavage.}, Author = {Klein, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0955-0674}, Journal = {Curr Opin Cell Biol}, Keywords = {Receptor Protein-Tyrosine Kinases;Synapses;Transcription Factors;10 Development;research support, non-u.s. gov't;Ephrin-A2;Signal Transduction;10 circuit formation;Receptor, EphA1;Animals;Humans;24 Pubmed search results 2008;review;Neurons}, Month = {4}, Nlm_Id = {8913428}, Number = {2}, Organization = {European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69117 Heidelberg, Germany. klein\@embl-heidelberg.de}, Pages = {196-203}, Pii = {S0955-0674(00)00197-6}, Pubmed = {11248553}, Title = {Excitatory Eph receptors and adhesive ephrin ligands}, Uuid = {A2F5110E-00E6-4675-9A8F-CA1B91EABB52}, Volume = {13}, Year = {2001}} @article{Klein:2003, Abstract = {0021-9738 Journal Article Review Review, Tutorial}, Author = {Klein, J. A. and Ackerman, S. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Clin Invest}, Keywords = {*Cell Cycle;Human;Neurodegenerative Diseases/*etiology;Reactive Oxygen Species/metabolism;08 Aberrant cell cycle;EE pdf;Cell Death;Support, U.S. Gov't, P.H.S.;Superoxides/metabolism;Animals;Neurons/physiology;*Oxidative Stress}, Number = {6}, Organization = {The Jackson Laboratory, Bar Harbor, Maine 04609, USA.}, Pages = {785-93}, Pubmed = {12639981}, Title = {Oxidative stress, cell cycle, and neurodegeneration}, Uuid = {1A7BC487-7F66-4CC6-8002-D9272879163A}, Volume = {111}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12639981}} @article{Klein:2002, Abstract = {Harlequin (Hq) mutant mice have progressive degeneration of terminally differentiated cerebellar and retinal neurons. We have identified the Hq mutation as a proviral insertion in the apoptosis-inducing factor (Aif) gene, causing about an 80\%reduction in AIF expression. Mutant cerebellar granule cells are susceptible to exogenous and endogenous peroxide-mediated apoptosis, but can be rescued by AIF expression. Overexpression of AIF in wild-type granule cells further decreases peroxide-mediated cell death, suggesting that AIF serves as a free radical scavenger. In agreement, dying neurons in aged Hq mutant mice show oxidative stress. In addition, neurons damaged by oxidative stress in both the cerebellum and retina of Hq mutant mice re-enter the cell cycle before undergoing apoptosis. Our results provide a genetic model of oxidative stress-mediated neurodegeneration and demonstrate a direct connection between cell cycle re-entry and oxidative stress in the ageing central nervous system. 0028-0836 Journal Article}, Author = {Klein, J. A. and Longo-Guess, C. M. and Rossmann, M. P. and Seburn, K. L. and Hurd, R. E. and Frankel, W. N. and Bronson, R. T. and Ackerman, S. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {Nature}, Keywords = {Animals;Cell Survival/drug effects;Cells, Cultured;Apoptosis/drug effects;Mice, Mutant Strains;Aging;Hydrogen Peroxide/pharmacology;Phenotype;Membrane Proteins/*deficiency/*genetics/metabolism;Flavoproteins/*genetics/metabolism;Retina/metabolism/*pathology;EE pdf;Cell Cycle/drug effects;Neurons/drug effects/metabolism/*pathology;Mutation/*genetics;Lipid Peroxidation;08 Aberrant cell cycle;*Oxidative Stress/drug effects;Purkinje Cells/metabolism/pathology;Down-Regulation;Cerebellum/drug effects/metabolism/*pathology;Support, U.S. Gov't, P.H.S.;Mice;Microscopy, Electron;Free Radical Scavengers/metabolism;Polymerase Chain Reaction;Catalase/metabolism;Glutathione/metabolism}, Number = {6905}, Organization = {The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA.}, Pages = {367-74}, Title = {The harlequin mouse mutation downregulates apoptosis-inducing factor}, Uuid = {24A4FF15-0393-4007-925A-5CFC42DA3471}, Volume = {419}, Year = {2002}, url = {papers/Klein_Nature2002.pdf}} @article{Klement:1972, Author = {Klement, V. and Nicolson, M. O. and Gilden, R. V. and Oroszlan, S. and Sarma, P. S. and Rongey, R. W. and Gardner, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0090-0028}, Journal = {Nat New Biol}, Keywords = {Microscopy, Electron;Oncogenic Viruses;Antigens, Viral;Animals;RNA Viruses;Rats;15 Retrovirus mechanism;Uridine;Retroviridae;Sarcoma, Experimental;Cell Line;Immunodiffusion;Sarcoma Viruses, Avian;DNA Nucleotidyltransferases;24 Pubmed search results 2008;Bromodeoxyuridine;Chickens;15 ERVs retroelements;Tritium;Cell Transformation, Neoplastic}, Medline = {73020642}, Month = {8}, Nlm_Id = {0410463}, Number = {86}, Pages = {234-7}, Pubmed = {4342693}, Title = {Rat C-type virus induced in rat sarcoma cells by 5-bromodeoxyuridine}, Uuid = {8DFFB767-4328-11DB-A5D2-000D9346EC2A}, Volume = {238}, Year = {1972}} @article{Klesney-Tait:2006, Abstract = {TREM proteins are a family of cell surface receptors that participate in diverse cell processes, including inflammation, bone homeostasis, neurological development and coagulation. TREM-1, the first to be identified, acts to amplify inflammation. Other TREM proteins regulate the differentiation and function of macrophages, microglia, dendritic cells, osteoclasts and platelets. Here we discuss the state of the field, putative ligands of TREM proteins and the challenges that remain in understanding TREM biology.}, Author = {Klesney-Tait, Julia and Turnbull, Isaiah R. and Colonna, Marco}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1529-2908}, Journal = {Nat Immunol}, Keywords = {14 Immune;11 Glia;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {100941354}, Number = {12}, Organization = {Washington University School of Medicine, Department of Pathology and Immunology, Saint Louis, Missouri 63110, USA.}, Pages = {1266-73}, Pii = {ni1411}, Pubmed = {17110943}, Title = {The TREM receptor family and signal integration}, Uuid = {92CCE245-9D8E-441D-9EC6-540EF121B04F}, Volume = {7}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ni1411}} @article{Kloss:1999, Abstract = {Integrins are a large family of heterodimeric glycoproteins that play a crucial role in cell adhesion during development, inflammation, and tissue repair. In the current study, we investigated the localization of different integrin subunits in the mouse facial motor nucleus and their regulation after transection of the facial nerve. In the normal mouse brain, there was clear immunoreactivity for alpha5-, alpha6-, and beta1-integrin subunits on blood vessel endothelia and for alphaM- and beta2-subunits on resting parenchymal microglia. Facial nerve transection led to an up-regulation of the beta1-subunit on the axotomized neurons and an increase in the alpha4-, alpha5-, alpha6-, beta1-, alphaM-, alphaX-, and beta2-subunits on the adjacent, activated microglia. Quantification of the microglial integrins revealed two different expression patterns. The subunits alpha5 and alpha6 showed a monophasic increase with a maximum at day 4, the alphaM-subunit a biphasic regulation, with an early peak at day 1 and an elevated plateau between day 14 and 42. At day 14, there was also an influx of lymphocytes immunoreactive for the alpha4beta1- and alphaLbeta2-integrins, which aggregated at sites of neural debris and phagocytotic microglia. This finding was accompanied by a significant increase of the alpha5beta1-integrin on blood vessel endothelia. In summary, facial axotomy is followed by a strong and cell-type-specific expression of integrins on the affected neurons and on surrounding microglia, lymphocytes, and vascular endothelia. The presence of several, strikingly different temporal patterns suggests a selective involvement of these molecules in the different adhesive events during regeneration in the central nervous system.}, Author = {Kloss, C. U. and Werner, A. and Klein, M. A. and Shen, J. and Menuz, K. and Probst, J. C. and Kreutzberg, G. W. and Raivich, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Nerve Regeneration;Organ Specificity;Facial Nerve Injuries;Antibodies, Monoclonal;Brain;Animals;Phagocytosis;Dimerization;Base Sequence;Molecular Sequence Data;Integrins;RNA, Messenger;Spleen;Retrograde Degeneration;11 Glia;Microscopy, Immunoelectron;Cell Adhesion;Gene Expression Regulation;Comparative Study;Facial Nerve;Time Factors;Female;Microglia;Endothelium, Vascular;Lymphocytes;Microscopy, Confocal;Support, Non-U.S. Gov't;Fluorescent Antibody Technique, Indirect;Image Processing, Computer-Assisted;Polymerase Chain Reaction;Nerve Tissue Proteins;Astrocytes;Mice}, Medline = {99333552}, Month = {8}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Neuromorphology, Max-Planck Institute for Neurobiology, D-82152 Martinsried, Germany.}, Pages = {162-78}, Pii = {10.1002/(SICI)1096-9861(19990816)411:1<162::AID-CNE12>3.0.CO;2-W}, Pubmed = {10404114}, Title = {Integrin family of cell adhesion molecules in the injured brain: regulation and cellular localization in the normal and regenerating mouse facial motor nucleus}, Uuid = {B022642D-3E79-45C4-AEC4-783601F9509B}, Volume = {411}, Year = {1999}} @article{Klueva:2003, Abstract = {Lateral amygdala (LA) activity during synchronized-epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple-site extra- and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4-aminopyridine (50 microm) induced epileptiform discharges in all regions under study. Slow interictal-like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal-like activity. Disconnection of the amygdala resulted in de-synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal-like activity was intracellularly reflected in LA projection neurons as gamma-aminobutyric acid (GABA)A/B receptor-mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal-like activity in all areas under study. We conclude that interictal-like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons.}, Author = {Klueva, Julia and Munsch, Thomas and Albrecht, Doris and Pape, Hans-Christian C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Amygdala;Epilepsy;24 Pubmed search results 2008;GABA Antagonists;Male;Reaction Time;Animals;Extracellular Space;Hippocampus;In Vitro;Propanolamines;Electric Stimulation;Entorhinal Cortex;Synapses;Potassium;Phosphinic Acids;21 Epilepsy;Carbenoxolone;Comparative Study;Evoked Potentials;Action Potentials;Anesthetics, Local;Tetrodotoxin;Time Factors;Rats;Anti-Ulcer Agents;Bicuculline;21 Neurophysiology;Research Support, Non-U.S. Gov't;Rats, Wistar;Dissection;Neurons;4-Aminopyridine}, Month = {11}, Nlm_Id = {8918110}, Number = {10}, Organization = {Institut f{\"u}r Physiologie, Medizinische Fakult{\"a}t, Otto-von-Guericke-Universit{\"a}t Magdeburg, D-39120 Magdeburg, Germany.}, Pages = {2779-91}, Pii = {2984}, Pubmed = {14656327}, Title = {Synaptic and non-synaptic mechanisms of amygdala recruitment into temporolimbic epileptiform activities}, Uuid = {924633A2-683E-4CEC-ADBD-C0188918D260}, Volume = {18}, Year = {2003}} @article{Kluge:1998, Abstract = {In vitro tract tracing allowing for continuous observation of the perforant path is a crucial prerequisite for experimental studies on the entorhinal-hippocampal interaction in an organotypic slice culture containing the entorhinal cortex, the perforant path, and the dentate gyrus (OEHSC). We prepared horizontal slices of the temporal entorhinal-hippocampal region of the rat on a vibratome, and the perforant path axons were traced by application of the fluorescent tracer Mini Ruby on the entorhinal cortex. After 2 days in vitro (div), the perforant path became visible in most cultures. Entorhinal neurons and single perforant fibers could be followed to the outer molecular layers of the dentate gyrus by in vitro fluorescence microscopy and it was possible to monitor the perforant path directly over a period of 25 div. Moreover, ultrastructural analysis proved the existence of traced perforant path boutons forming synapses with spines and dendritic shafts in the outer molecular layers of the dentate gyrus. Transsection of the prelabelled perforant path in vitro resulted in anterograde degeneration and subsequent phagocytosis of axonal material by activated microglial cells in the zone of denervation. In conclusion, in vitro tracing demonstrates the maintenance of the entorhinal-hippocampal pathway in OEHSCs and permits monitoring of dynamic changes in the prelabeled perforant path after various lesion paradigms, e.g., transsection or neurotoxin treatment. This approach permits further studies on the efficacy of neuroprotectants, cytokines, and growth factors in the treatment of lesion-induced neuronal degeneration.}, Author = {Kluge, A. and Hailer, N. P. and Horvath, T. L. and Bechmann, I. and Nitsch, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {1050-9631}, Journal = {Hippocampus}, Keywords = {Phagocytosis;Nerve Degeneration;Animals;Rats;Entorhinal Cortex;Axons;Perforant Pathway;Rats, Wistar;11 Glia;Microscopy, Fluorescence;Organ Culture Techniques;Dendrites;Neurons;Neuroglia;Dentate Gyrus;Microscopy, Electron;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {98178709}, Nlm_Id = {9108167}, Number = {1}, Organization = {Department of Cell and Neurobiology, Institute of Anatomy, Humboldt University Hospital (Charit{\'e}), Berlin, Germany.}, Pages = {57-68}, Pubmed = {9519887}, Title = {Tracing of the entorhinal-hippocampal pathway in vitro}, Uuid = {3372E16D-4486-4E8A-ACAF-2BC6A4A14BF3}, Volume = {8}, Year = {1998}} @article{Klump:2001, Abstract = {Retroviral vector-mediated expression of the homeoboxgene, HoxB4, in hematopoietic cells has been reported to mediate a benign expansion of gene-modified hematopoietic stem and precursor cells in vivo. In the present study, we used a novel coexpression strategy for coordinated expression of HoxB4 along with a cytoplasmic protein from a retroviral vector. The novel coexpression strategy, based on cotranslational protein separation mediated by the 2A sequence of foot-and-mouth disease virus (FMDV), allows an indirect quantification of HoxB4 expression levels when inserting a reporter such as the enhanced green fluorescent protein (GFP) in the retroviral vector. Presence of the 2A sequence did not interfere with the correct subcellular localization of HoxB4 (nuclear) and GFP (cytoplasmic), nor with the titer of bicistronic vectors, and mediated functional long-term coexpression (at least 1 year) of GFP and HoxB4 after transplantation of transduced mouse bone marrow cells in mice.}, Author = {Klump, H. and Schiedlmeier, B. and Vogt, B. and Ryan, M. and Ostertag, W. and Baum, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Transduction, Genetic;Animals;Fluorescent Antibody Technique;Cytoplasm;Female;Mice, Inbred C57BL;Retroviridae;11 Glia;Male;Time Factors;Aphthovirus;Green Fluorescent Proteins;Polioviruses;Genetic Vectors;Gene Therapy;Blotting, Western;Cell Nucleus;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {21313499}, Month = {5}, Nlm_Id = {9421525}, Number = {10}, Organization = {Heinrich-Pette-Institut for Experimental Virology and Immunology, Martinistrasse 52, D-20251 Hamburg, Germany.}, Pages = {811-7}, Pubmed = {11420646}, Title = {Retroviral vector-mediated expression of HoxB4 in hematopoietic cells using a novel coexpression strategy}, Uuid = {1E9F9CDB-7744-4712-88D5-E3C4838FCB72}, Volume = {8}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301447}} @article{Knowles:1989, Author = {Knowles, W. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0891-1150}, Journal = {Cleve Clin J Med}, Keywords = {Epilepsy;Neurons;Synapses;24 Pubmed search results 2008;21 Epilepsy;21 Neurophysiology;Neural Inhibition;Animals;Disease Models, Animal;Brain;Humans;review}, Medline = {89275462}, Nlm_Id = {8703441}, Pages = {S221-5}, Pubmed = {2659212}, Title = {Aspects of epileptogenesis: maturation of neuronal circuits}, Uuid = {361690BD-6637-42DA-84CA-B9F211F2DA03}, Volume = {56 Suppl Pt 2}, Year = {1989}} @article{Knyazeva:2001, Abstract = {Visual corpus callosum (CC) preferentially interconnects neurons selective for similar stimulus orientation near the representations of the vertical meridian. These properties allow studying the CC functionality with EEG coherence analysis. Iso-oriented and orthogonally-oriented gratings were presented to the two hemifields, either close to the vertical meridian or far from it. In animals with intact CC, and in man, interhemispheric coherence (ICoh) increased only with iso-oriented gratings presented near or crossing the vertical meridian. The increase was localized to occipital electrodes and was specific for the beta-gamma frequency band. Visual-stimulus induced changes in ICoh were studied in patients with early pathologies of the visual areas. From a girl with abnormal vision and severe bilateral lesion of the primary visual areas at 3 weeks, after premature birth at 30 weeks, we obtained no ICoh response until 9 years. In control children visual stimulation increased occipital ICoh at 6-7 years. From a young man having suffered similar lesions when he was 9 months older than the girl, no consistent increase in ICoh could be obtained. In a 14-year-old girl with congenital visual agnosia, no visible lesions, but with a temporal-occipital epileptic focus, ICoh responses were evoked both by iso-oriented, and by orthogonally-oriented gratings. In a young man with bilateral parieto-occipital microgyria extending into the calcarine sulcus, visual stimuli increased ICoh as in normal individuals, but the response was weaker. These cases are discussed in terms of development of CC connections and point to a variety of plastic changes in the cortical connectivity of children.}, Author = {Knyazeva, M. G. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0165-0173}, Journal = {Brain Res Brain Res Rev}, Keywords = {Human;Visual Perception;review, tutorial;review;Female;Child;Infant;Not relevant;11 Glia;Male;Brain Injuries;Evoked Potentials, Visual;Support, Non-U.S. Gov't;Nervous System Malformations;Adult;Vision Disorders;Infant, Newborn;Corpus Callosum;Visual Cortex;Electroencephalography;Adolescent}, Medline = {21548859}, Month = {10}, Nlm_Id = {8908638}, Number = {2-3}, Organization = {Institute of Cellular Biology and Morphology, University of Lausanne, Rue du Bugnon 9, 1005, Lausanne, Switzerland. maria.knyazeva\@ibcm.unil.ch}, Pages = {119-28}, Pii = {S016501730100087X}, Pubmed = {11690608}, Title = {EEG coherence studies in the normal brain and after early-onset cortical pathologies}, Uuid = {F7B61936-9A75-44BC-8F58-3D3F84D125BD}, Volume = {36}, Year = {2001}} @article{Knyazeva:1999, Abstract = {We analyzed the coherence of electroencephalographic (EEG) signals recorded symmetrically from the two hemispheres, while subjects (n = 9) were viewing visual stimuli. Considering the many common features of the callosal connectivity in mammals, we expected that, as in our animal studies, interhemispheric coherence (ICoh) would increase only with bilateral iso-oriented gratings located close to the vertical meridian of the visual field, or extending across it. Indeed, a single grating that extended across the vertical meridian significantly increased the EEG ICoh in normal adult subjects. These ICoh responses were obtained from occipital and parietal derivations and were restricted to the gamma frequency band. They were detectable with different EEG references and were robust across and within subjects. Other unilateral and bilateral stimuli, including identical gratings that were effective in anesthetized animals, did not affect ICoh in humans. This fact suggests the existence of regulatory influences, possibly of a top-down kind, on the pattern of callosal activation in conscious human subjects. In addition to establishing the validity of EEG coherence analysis for assaying cortico-cortical connectivity, this study extends to the human brain the finding that visual stimuli cause interhemispheric synchronization, particularly in frequencies of the gamma band. It also indicates that the synchronization is carried out by cortico-cortical connection and suggests similarities in the organization of visual callosal connections in animals and in man.}, Author = {Knyazeva, M. G. and Kiper, D. C. and Vildavski, V. Y. and Despland, P. A. and Maeder-Ingvar, M. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Laterality;Photic Stimulation;Electroencephalography;Adult;Human;Female;Algorithms;Not relevant;clinical trial;11 Glia;Brain Mapping;Cortical Synchronization;Support, Non-U.S. Gov't;Brain;Male}, Medline = {20070014}, Month = {12}, Nlm_Id = {0375404}, Number = {6}, Organization = {Research Institute of Developmental Physiology, 119121 Pogodinskaya 8-2, Moscow, Russia.}, Pages = {3095-107}, Pubmed = {10601444}, Title = {Visual stimulus-dependent changes in interhemispheric EEG coherence in humans}, Uuid = {CC0295FA-DD64-4EB8-BE96-64DCB1025676}, Volume = {82}, Year = {1999}} @article{Knyazeva:2002, Abstract = {In one of two patients (MS and FJ) with bilateral, early-onset lesion of the primary visual cortex, Kiper et al. (2002) observed a considerable degree of functional recovery. To clarify the physiological mechanisms involved in the recovery, we used fMRI and quantitative EEG to study both patients. The fMRI investigations indicated that in both patients, isolated islands of the primary visual cortex are functioning, in the right hemisphere in MS and in the left in FJ. The functional recovery observed in MS roughly correlated with the functional maturation of interhemispheric connections and might reflect the role of corticocortical connectivity in visual perception. The functionality of interhemispheric connections was assessed by analyzing the changes in occipital inter-hemispheric coherence of EEG signals (ICoh) evoked by moving gratings. In the patient MS, this ICoh response was present at 7:11 y and was more mature at 9:2 y. In the more visually impaired patient, FJ, a consistent increase in ICoh to visual stimuli could not be obtained, possibly because of the later occurrence of the lesion.}, Author = {Knyazeva, M. G. and Maeder, P. and Kiper, D. C. and Deonna, T. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Journal = {Neural Plast}, Keywords = {Form Perception;Human;Magnetic Resonance Imaging;Photic Stimulation;comment;Recovery of Function;Neuronal Plasticity;Age of Onset;Female;Child;Not relevant;11 Glia;Male;Vision;Support, Non-U.S. Gov't;Visual Cortex;Electroencephalography;Adolescent}, Medline = {22346600}, Nlm_Id = {100883417}, Number = {1}, Organization = {Institut de Biologie Cellulaire et de Morphologie, University of Lausanne, Switzerland.}, Pages = {27-40}, Pubmed = {12458787}, Title = {Vision after early-onset lesions of the occipital cortex: II. Physiological studies}, Uuid = {A872AB69-A67E-413A-9285-9D2207952BC5}, Volume = {9}, Year = {2002}} @article{Kobari:2000, Abstract = {The aim of the present report is to describe clinically relevant culture conditions that support the expansion of primitive hematopoietic progenitors/stem cells, with maintenance of their hematopoietic potential as assessed by in vitro assays and the NOD-SCID in vivo repopulating capacity.CD34(+) cord blood (CB) cells were cultured in serum-free medium containing stem cell factor, Flt3 ligand, megakaryocyte growth and development factor, and granulocyte colony-stimulating factor. After 14 days, the primitive functions of expanded and nonexpanded cells were determined in vitro using clonogenic cell (colony-forming cells, long-term culture initiating cell [LTC-IC], and extended [E]-LTC-IC) and lymphopoiesis assays (NK, B, and T) and in vivo by evaluating long-term engraftment of the bone marrow of NOD-SCID mice. The proliferative potential of these cells also was assessed by determining their telomere length and telomerase activity.Levels of expansion were up to 1,613-fold for total cells, 278-fold for colony-forming unit granulocyte-macrophage, 47-fold for LTC-IC, and 21-fold for E-LTC-IC. Lymphoid B-, NK, and T-progenitors could be detected. When the expanded populations were transplanted into NOD-SCID mice, they were able to generate myeloid progenitors and lymphoid cells for 5 months. These primitive progenitors engrafted the NOD-SCID bone marrow, which contained LTC-IC at the same frequency as that of control transplanted mice, with conservation of their clonogenic capacity. Moreover, human CD34(+)CDl9(-) cells sorted from the engrafted marrow were able to generate CD19(+) B-cells, CD56(+)CD3(-) NK cells, and CD4(+)CD8(+)alphabetaTCR(+) T-cells in specific cultures. Our expansion protocol also maintained the telomere length in CD34(+) cells, due to an 8.8-fold increase in telomerase activity over 2 weeks of culture.These experiments provide strong evidence that expanded CD34(+) CB cells retain their ability to support long-term hematopoiesis, as shown by their engraftment in the NOD-SCID model, and to undergo multilineage differentiation along all myeloid and the B-, NK, and T-lymphoid pathways. The expansion protocol described here appears to maintain the hematopoietic potential of CD34(+) CB cells, which suggests its relevance for clinical applications.}, Author = {Kobari, L. and Pflumio, F. and Giarratana, M. and Li, X. and Titeux, M. and Izac, B. and Leteurtre, F. and Coulombel, L. and Douay, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0301-472X}, Journal = {Exp Hematol}, Keywords = {T-Lymphocytes;Cell Differentiation;Mice, Inbred NOD;Animals;Cells, Cultured;Humans;Granulocytes;Lymphocytes;Mice, SCID;Granulocyte Colony-Stimulating Factor;B-Lymphocytes;11 Glia;Antigens, CD34;Hematopoietic Stem Cell Transplantation;Killer Cells, Natural;Hematopoiesis;Thrombopoietin;Fetal Blood;Stem Cell Factor;Hematopoietic Stem Cells;Membrane Proteins;Graft Survival;Mice;Research Support, Non-U.S. Gov't}, Medline = {20582384}, Month = {12}, Nlm_Id = {0402313}, Number = {12}, Organization = {INSERM U 417, H\^{o}pital Saint-Antoine, Paris, France.}, Pages = {1470-80}, Pii = {S0301472X00005579}, Pubmed = {11146169}, Title = {In vitro and in vivo evidence for the long-term multilineage (myeloid, B, NK, and T) reconstitution capacity of ex vivo expanded human CD34(+) cord blood cells}, Uuid = {3BE3F751-1C76-4770-A2E6-63BEDBE1DD14}, Volume = {28}, Year = {2000}} @article{Kobayashi:2006, Abstract = {Grey matter heterotopia are commonly associated with refractory epilepsy. Depth electrodes recordings have shown that epileptiform activity can be generated within these lesions, and also at a distance in the neocortex. Heterotopia seem to be part of a more complex circuitry involving also the surrounding and distant cerebral cortex. Blood oxygenation level-dependent (BOLD) changes to interictal spikes using continuous EEG and functional MRI (EEG-fMRI) can help to understand non-invasively the mechanisms of epileptogenicity in these patients. We studied 14 patients with epilepsy and heterotopia using simultaneous recording of EEG-fMRI. EEG was continuously acquired from inside the scanner during 2 h sessions. Epileptic spikes were visually identified in the filtered EEG and each type of spike determined one EEG-fMRI study. We looked at positive (activation) and negative (deactivation) changes in the BOLD signal. Eleven patients had nodular heterotopia and three band heterotopia. Four patients had more than one type of spikes, with a total of 26 EEG-fMRI studies. We excluded three with less than three spikes, and therefore a total of 23 studies (12 with nodular and 11 with band heterotopia) were analysed. Nodular heterotopia: Activation was present in nine studies, with involvement of the heterotopia or surrounding cortex in six, three of which had concomitant distant activation. Deactivation was also observed in nine studies, with involvement of the heterotopia and surrounding cortex in four, three of which had concomitant distant deactivation. Band heterotopia: Activation was present in all 11 studies, and always involved the heterotopia and surrounding cortex, 9 of which had concomitant distant activation. Deactivation was also observed in all 11 studies, with involvement of both the heterotopia and surrounding cortex, in addition to distant deactivation in 5 studies. EEG-fMRI studies reveal, non-invasively, metabolic responses in the heterotopia despite the fact that spikes are generated in the neocortex. The responses, activation or deactivation, had different correlation with the lesion and surrounding or distant cortex, activation reflecting intense neuronal activity, or excitation, and deactivation a possible distant (extra-lesional) inhibition. EEG-fMRI may become a useful tool to understand the epileptogenicity of such malformations.}, Author = {Kobayashi, Eliane and Bagshaw, Andrew P. and Grova, Christophe and Gotman, Jean and Dubeau, Fran\c{c}ois}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1460-2156}, Journal = {Brain}, Keywords = {Epilepsy;Electroencephalography;Research Support, Non-U.S. Gov't;21 Dysplasia-heterotopia;21 Neurophysiology;Magnetic Resonance Imaging;Female;Choristoma;Male;Humans;Brain;24 Pubmed search results 2008;21 Epilepsy}, Month = {2}, Nlm_Id = {0372537}, Number = {Pt 2}, Organization = {Montreal Neurological Institute and Hospital, McGill University, Montreal, Canada. eliane.kobayashi\@mail.mcgill.ca}, Pages = {366-74}, Pii = {awh710}, Pubmed = {16339793}, Title = {Grey matter heterotopia: what EEG-fMRI can tell us about epileptogenicity of neuronal migration disorders}, Uuid = {8AA1B7E4-ECBD-41E8-8B83-C3C065FE28DD}, Volume = {129}, Year = {2006}, url = {papers/Kobayashi_Brain2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/brain/awh710}} @article{Koenigsknecht-Talboo:2005, Abstract = {Microglia undergo a phenotypic activation in response to fibrillar beta-amyloid (fAbeta) deposition in the brains of Alzheimer's disease (AD) patients, resulting in their elaboration of inflammatory molecules. Despite the presence of abundant plaque-associated microglia in the brains of AD patients and in animal models of the disease, microglia fail to efficiently clear fAbeta deposits. However, they can be induced to do so during Abeta vaccination therapy attributable to anti-Abeta antibody stimulation of IgG receptor (FcR)-mediated phagocytic clearance of Abeta plaques. We report that proinflammatory cytokines attenuate microglial phagocytosis stimulated by fAbeta or complement receptor 3 and argue that this may, in part, underlie the accumulation of fAbeta-containing plaques within the AD brain. The proinflammatory suppression of fAbeta-elicited phagocytosis is dependent on nuclear factor kappaB activation. Significantly, the proinflammatory cytokines do not inhibit phagocytosis elicited by antibody-mediated activation of FcR, which may contribute to the efficiency of Abeta vaccination-based therapy. Importantly, the proinflammatory suppression of fAbeta phagocytosis can be relieved by the coincubation with anti-inflammatory cytokines, cyclooxygenase inhibitors, ibuprofen, or an E prostanoid receptor antagonist, suggesting that proinflammatory cytokines induce the production of prostaglandins, leading to an E prostanoid receptor-dependent inhibition of phagocytosis. These findings support anti-inflammatory therapies for the treatment of AD.}, Author = {Koenigsknecht-Talboo, Jessica and Landreth, Gary E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8102140}, Number = {36}, Organization = {Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.}, Pages = {8240-9}, Pii = {25/36/8240}, Pubmed = {16148231}, Title = {Microglial phagocytosis induced by fibrillar beta-amyloid and IgGs are differentially regulated by proinflammatory cytokines}, Uuid = {99C72EAB-8DB4-4974-9E13-9E497D74CC87}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1808-05.2005}} @article{Koester:1992, Abstract = {We demonstrate in rat neocortex that the distinct laminar arrangements of the apical dendrites of two classes of layer 5 projection neurons, callosal and corticotectal, do not arise de novo, but are generated later in development from a common tall pyramidal morphology. Neurons of each class initially elaborate an apical dendrite in layer 1. Layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons later lose the segments of their apical dendrite superficial to layer 4, generating their characteristic short pyramidal morphology. The apical dendrite of layer 5 callosal neurons is actively eliminated, rather than passively displaced, as superficial cortical layers expand. Corticotectal neurons and callosal neurons superficial to layer 5 maintain their apical dendrite to layer 1. Therefore, this selective dendritic loss occurs in a neuron class-specific manner and, within the callosal population, in a lamina-specific manner. Based on our additional observations and other studies, this phenomenon can be extended to other types of cortical projection neurons. These findings show that selective dendritic elimination plays a major role in shaping the functional architecture characteristic of the adult cortex.}, Author = {Koester, S. E. and O'Leary, D. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Embryo and Fetal Development;10 Development;Dendrites;Neuronal Plasticity;10 Spiny stellate;Support, U.S. Gov't, P.H.S.;Animals, Newborn;10 Structural plasticity;Support, Non-U.S. Gov't;Animals;Cerebral Cortex;Neurons;Beta}, Medline = {92211398}, Month = {4}, Nlm_Id = {8102140}, Number = {4}, Organization = {Molecular Neurobiology Laboratory, Salk Institute, La Jolla, California 92037.}, Pages = {1382-93}, Pubmed = {1556599}, Title = {Functional classes of cortical projection neurons develop dendritic distinctions by class-specific sculpting of an early common pattern}, Uuid = {3A581CF5-00AF-11DB-9E68-000D9346EC2A}, Volume = {12}, Year = {1992}, url = {papers/Koester_JNeurosci1992.pdf}} @article{Kohwi:2005, Abstract = {The subventricular zone (SVZ) produces different subclasses of olfactory bulb (OB) interneurons throughout life. Little is known about the molecular mechanisms controlling the production of different types of interneurons. Here we show that most proliferating adult SVZ progenitors express the transcription factor Pax6, but only a small subpopulation of migrating neuroblasts and new OB interneurons derived from these progenitors retains Pax6 expression. To elucidate the cell-autonomous role of Pax6 in OB neurogenesis, we transplanted green fluorescent protein-expressing embryonic forebrain progenitors of the dorsal lateral ganglionic eminence from Pax6 mutant Small Eye (Pax6(Sey/Sey)) mice into the SVZ of adult wild-type mice. Pax6(Sey/Sey) progenitors produce neuroblasts capable of migrating into the OB but fail to generate dopaminergic periglomerular and superficial granule cells. Interestingly, superficial granule neurons also express mRNA for tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Our data show that SVZ neuroblasts are heterogeneous and that Pax6 is required in a cell-autonomous manner for the production of cells in the dopaminergic lineage.}, Author = {Kohwi, Minoree and Osumi, Noriko and Rubenstein, John L. R. and Alvarez-Buylla, Arturo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Month = {7}, Nlm_Id = {8102140}, Number = {30}, Organization = {Department of Neurological Surgery, Program in Developmental and Stem Cell Biology, University of California, San Francisco, California 94143, USA.}, Pages = {6997-7003}, Pii = {25/30/6997}, Pubmed = {16049175}, Title = {Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb}, Uuid = {AD8B0FB7-A3E5-11DA-AB00-000D9346EC2A}, Volume = {25}, Year = {2005}, url = {papers/Kohwi_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1435-05.2005}} @article{Koizumi:2006, Abstract = {The ability of the mature mammalian nervous system to continually produce neuronal precursors is of considerable importance, as manipulation of this process might one day permit the replacement of cells lost as a result of injury or disease. In mammals, the anterior subventricular zone (SVZa) region is one of the primary sites of adult neurogenesis. Here we show that doublecortin (DCX), a widely used marker for newly generated neurons, when deleted in mice results in a severe morphological defect in the rostral migratory stream and delayed neuronal migration that is independent of direction or responsiveness to Slit chemorepulsion. DCX is required for nuclear translocation and maintenance of bipolar morphology during migration of these cells. Our data identifies a critical function for DCX in the movement of newly generated neurons in the adult brain.}, Author = {Koizumi, Hiroyuki and Higginbotham, Holden and Poon, Tiffany and Tanaka, Teruyuki and Brinkman, Brendan C. and Gleeson, Joseph G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Mice, Inbred BALB C;Microtubule-Associated Proteins;Cell Differentiation;Animals;Gene Expression Regulation, Developmental;Phenotype;Chemotaxis;Protein Transport;Female;Mice, Transgenic;Neurites;Mice, Inbred C57BL;Cell Movement;Cell Proliferation;Male;Neuropeptides;Prosencephalon;Active Transport, Cell Nucleus;Cell Shape;Mice, Knockout;Neurons;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Stem Cells;Nerve Tissue Proteins}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {Neurogenetics Laboratory, Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.}, Pages = {779-86}, Pii = {nn1704}, Pubmed = {16699506}, Title = {Doublecortin maintains bipolar shape and nuclear translocation during migration in the adult forebrain}, Uuid = {CAFD7FBB-DA6F-47BF-ABBF-631E5BB4B1FC}, Volume = {9}, Year = {2006}, url = {papers/Koizumi_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1704}} @article{Koizumi:2007, Abstract = {Microglia, brain immune cells, engage in the clearance of dead cells or dangerous debris, which is crucial to the maintenance of brain functions. When a neighbouring cell is injured, microglia move rapidly towards it or extend a process to engulf the injured cell. Because cells release or leak ATP when they are stimulated or injured, extracellular nucleotides are thought to be involved in these events. In fact, ATP triggers a dynamic change in the motility of microglia in vitro and in vivo, a previously unrecognized mechanism underlying microglial chemotaxis; in contrast, microglial phagocytosis has received only limited attention. Here we show that microglia express the metabotropic P2Y(6) receptor whose activation by endogenous agonist UDP triggers microglial phagocytosis. UDP facilitated the uptake of microspheres in a P2Y(6)-receptor-dependent manner, which was mimicked by the leakage of endogenous UDP when hippocampal neurons were damaged by kainic acid in vivo and in vitro. In addition, systemic administration of kainic acid in rats resulted in neuronal cell death in the hippocampal CA1 and CA3 regions, where increases in messenger RNA encoding P2Y(6) receptors that colocalized with activated microglia were observed. Thus, the P2Y(6) receptor is upregulated when neurons are damaged, and could function as a sensor for phagocytosis by sensing diffusible UDP signals, which is a previously unknown pathophysiological function of P2 receptors in microglia.}, Author = {Koizumi, and Shigemoto-Mogami, and Nasu-Tada, and Shinozaki, and Ohsawa, and Tsuda, and Joshi, and Jacobson, and Kohsaka, and Inoue,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {0410462}, Organization = {[1] Division of Pharmacology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya, Tokyo 158-8501, Japan [2] Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3893, Japan [3] These authors contributed equally to this work.}, Pii = {nature05704}, Pubmed = {17410128}, Title = {UDP acting at P2Y(6) receptors is a mediator of microglial phagocytosis}, Uuid = {4A43664C-6A83-43B1-B669-2485BF0E03B5}, Year = {2007}, url = {papers/Koizumi_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05704}} @article{Koizumi:2006a, Abstract = {The potential role of doublecortin (Dcx), encoding a microtubule-associated protein, in brain development has remained controversial. Humans with mutations show profound alterations in cortical lamination, whereas in mouse, RNAi-mediated knockdown but not germline knockout shows abnormal positioning of cortical neurons. Here, we report that the doublecortin-like kinase (Dclk) gene functions in a partially redundant pathway with Dcx in the formation of axonal projections across the midline and migration of cortical neurons. Dosage-dependent genetic effects were observed in both interhemispheric connectivity and migration of cortically and subcortically derived neurons. Surprisingly, RNAi-mediated knockdown of either gene results in similar migration defects. These results indicate the Dcx microtubule-associated protein family is required for proper neuronal migration and axonal wiring.}, Author = {Koizumi, Hiroyuki and Tanaka, Teruyuki and Gleeson, Joseph G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Microtubule-Associated Proteins;Animals;Gene Dosage;Gene Targeting;Aging;Congenital Abnormalities;Synaptic Transmission;Exons;Brain;Cell Movement;Embryo, Mammalian;Embryonic Development;Protein-Serine-Threonine Kinases;Axons;Embryo;Neuropeptides;Animals, Newborn;Mice, Inbred Strains;Mice, Knockout;Neurons;Cerebral Cortex;Protein Structure, Tertiary;Abnormalities;Mice;24 Pubmed search results 2008;Nerve Fibers;Corpus Callosum;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, La Jolla, California 93093, USA.}, Pages = {55-66}, Pii = {S0896-6273(05)01064-0}, Pubmed = {16387639}, Title = {Doublecortin-like kinase functions with doublecortin to mediate fiber tract decussation and neuronal migration}, Uuid = {BE358A3B-7250-4B40-9F5C-EA1B1F1C61F3}, Volume = {49}, Year = {2006}, url = {papers/Koizumi_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.10.040}} @article{Kokaia:2003, Abstract = {Evidence for neuronal self-repair following insults to the adult brain has been scarce until very recently. Ischaemic insults have now been shown to trigger neurogenesis from neural stem cells or progenitor cells located in the dentate subgranular zone, the subventricular zone lining the lateral ventricle, and the posterior periventricle adjacent to the hippocampus. New neurons migrate to the granule cell layer or to the damaged CA1 region and striatum, where they express morphological markers characteristic of those neurons that have died. Some evidence indicates that these neurons can re-establish connections and contribute to functional recovery. 0959-4388 Journal Article Review Review, Tutorial}, Author = {Kokaia, Z. and Lindvall, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Human;Cell Differentiation;Nerve Regeneration/*physiology;Signal Transduction;Animals;Humans;Recovery of Function;Neurons/*cytology/physiology;review, tutorial;Recovery of Function/*physiology;review;D pdf;Cell Movement;Telencephalon;Telencephalon/cytology/*growth &development/physiology;Nerve Regeneration;Support, Non-U.S. Gov't;Neurons;Brain Ischemia;06 Adult neurogenesis injury induced;Cell Movement/physiology;Stem Cells/*cytology/physiology;Cell Differentiation/physiology;Brain Ischemia/pathology/*physiopathology/therapy;24 Pubmed search results 2008;Stem Cells;Signal Transduction/physiology;Research Support, Non-U.S. Gov't}, Medline = {22482251}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Section of Restorative Neurology, Wallenberg Neuroscience Centre, University Hospital, BMC A-11 SE- 221 84, Lund, Sweden. zaal.kokaia\@neurol.lu.se}, Pages = {127-32}, Pii = {S0959438803000175}, Pubmed = {12593991}, Title = {Neurogenesis after ischaemic brain insults}, Uuid = {0B914C21-AA60-4BBA-A9D0-F3FDD711926F}, Volume = {13}, Year = {2003}, url = {papers/Kokaia_CurrOpinNeurobiol2003.pdf}} @article{Koketsu:2003, Abstract = {The concept that, after developmental periods, neocortical neurons become numerically stable and are normally nonrenewable has been challenged by a report of continuous neurogenesis in the association areas of the cerebral cortex in the adult Macaque monkey. Therefore, we have reexamined this issue in two different Macaque species using the thymidine analog bromodeoxyuridine (BrdU) as an indicator of DNA replication during cell division. We found several BrdU+/NeuN+ (neuronal nuclei) double-labeled cells, but cortical neurons, distinguished readily by their size and cytological and immunohistochemical properties, were not BrdU positive. We examined in detail the frontal cortex, where it is claimed that the largest daily addition of neurons has been made, but did not see migratory streams or any sign of addition of new neurons. Thus, we concluded that, in the normal condition, cortical neurons of adult primates, similar to other mammalian species, are neither supplemented nor renewable. 1529-2401 Journal Article}, Author = {Koketsu, D. and Mikami, A. and Miyamoto, Y. and Hisatsune, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {J Neurosci}, Keywords = {A pdf;Frontal Lobe/*cytology;Cell Division/physiology;Immunohistochemistry;Female;Antigens, Differentiation/biosynthesis;Macaca fascicularis;Regeneration/*physiology;Cell Count;Neurons/*cytology/metabolism;Neocortex/*cytology;Animals;Bromodeoxyuridine;Support, Non-U.S. Gov't;Age Factors;Macaca}, Number = {3}, Organization = {Department of Integrated Biosciences, University of Tokyo, Kashiwa, Chiba, Japan.}, Pages = {937-42}, Title = {Nonrenewal of neurons in the cerebral neocortex of adult macaque monkeys}, Uuid = {55FF24D0-CDF0-11D9-B244-000D9346EC2A}, Volume = {23}, Year = {2003}, url = {papers/Koketsu_JNeurosci2003.pdf}} @article{Kokoeva:2005, Abstract = {Ciliary neurotrophic factor (CNTF) induces weight loss in obese rodents and humans, and for reasons that are not understood, its effects persist after the cessation of treatment. Here we demonstrate that centrally administered CNTF induces cell proliferation in feeding centers of the murine hypothalamus. Many of the newborn cells express neuronal markers and show functional phenotypes relevant for energy-balance control, including a capacity for leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3). Coadministration of the mitotic blocker cytosine-beta-d-arabinofuranoside (Ara-C) eliminates the proliferation of neural cells and abrogates the long-term, but not the short-term, effect of CNTF on body weight. These findings link the sustained effect of CNTF on energy balance to hypothalamic neurogenesis and suggest that regulated hypothalamic neurogenesis in adult mice may play a previously unappreciated role in physiology and disease.}, Author = {Kokoeva, Maia V. and Yin, Huali and Flier, Jeffrey S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {01 Adult neurogenesis general}, Month = {10}, Nlm_Id = {0404511}, Number = {5748}, Organization = {Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, 99 Brookline Avenue, Boston, MA 02215, USA.}, Pages = {679-83}, Pii = {310/5748/679}, Pubmed = {16254185}, Title = {Neurogenesis in the hypothalamus of adult mice: potential role in energy balance}, Uuid = {EAD02836-C89B-47F9-A9B7-C19A7DB47B69}, Volume = {310}, Year = {2005}, url = {papers/Kokoeva_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1115360}} @article{Kolb:1987, Abstract = {Rats with complete removal of the cortex anterior to bregma in adulthood (frontal cortex) were compared behaviorally and neuroanatomically to rats with similar removals at 1, 5, or 10 days of age. The age at which animals received the cortical excision made a significant difference with respect to the development of the thalamus and the remaining cortex as well as the behavioral outcome in adulthood. There was a direct relationship between cortical thickness in adulthood and the age at surgery: the earlier the lesion the thinner the cortex. Part of this anatomical effect was acute, and could be observed within 24 h of surgery, but the major reduction in thickness was not observed until adolescence. Behaviorally, the animals were administered several tests including tongue extension, grooming, beam walking, swimming, and a spatial navigation task. Like the cortical measurements, the behavioral measurements showed a clear relationship between age at surgery and behavioral outcome: the earlier the lesion in infancy, the greater the behavioral impairments. Thus, whereas rats with lesions at 10 days of age showed behavioral sparing, relative to adult operates, on every measure, rats with lesions at 5 days of age performed at about the level of adult operates on most tests and rats with lesions at 1 day had more extensive behavioral impairments than all other groups. These results imply that the effects of cortical injury in infancy are tightly correlated with the precise level of neural maturation at the time of lesion.}, Author = {Kolb, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Behavior, Animal;Nerve Regeneration;Female;Rats;Body Weight;Organ Size;Motor Activity;Reaction Time;Animals;Male;Thalamus;Brain;Frontal Lobe}, Medline = {88077384}, Month = {9}, Nlm_Id = {8004872}, Number = {3}, Organization = {Department of Psychology, University of Lethbridge, Alta., Canada.}, Pages = {205-20}, Pubmed = {3689568}, Title = {Recovery from early cortical damage in rats. I. Differential behavioral and anatomical effects of frontal lesions at different ages of neural maturation}, Uuid = {BB0F0E6E-D24F-11D9-A0E9-000D9346EC2A}, Volume = {25}, Year = {1987}} @article{Kolb:1991, Abstract = {This study examined the possibility that the presence or absence of behavioral sparing following neonatal frontal lesions might be correlated with changes in the complexity of dendritic branching. Rats were given bilateral frontal lesions in either adulthood, the day of birth, or on day 10. Ninety days later the animals were trained in a spatial navigation task. The animals' brains were then processed for Golgi-Cox staining and the dendritic branching of the pyramidal cells in the parietal cortex was analyzed. Frontal cortical lesions in newborn rats produced a severe behavioral deficit in the water task whereas frontal removal at 10 days of age allowed sparing of function relative to adult operates (that is, the Kennard effect). Analysis of dendritic arbor in sensorimotor cortex revealed that the day-10 animals exhibited a dramatic proliferation of dendritic arbor relative to control rats. In contrast, the day-1 animals had slightly less dendritic branching than control animals. Rats with frontal lesions in adulthood showed a small, but significant, increase in dendritic branching. The correlation between behavioral sparing and the increase in dendritic arborization following neonatal lesions may be illustrative of a general mechanism underlying the Kennard effect.}, Author = {Kolb, B. and Gibb, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Frontal Lobe;Rats;Neuronal Plasticity;Synaptic Transmission;Orientation;Male;Dendrites;Nerve Regeneration;Animals, Newborn;Escape Reaction;Cerebral Cortex;Discrimination Learning;Social Environment;Mental Recall;24 Pubmed search results 2008;Brain Mapping}, Medline = {91315735}, Month = {4}, Nlm_Id = {8004872}, Number = {1}, Organization = {Department of Psychology, University of Lethbridge, Canada.}, Pages = {51-6}, Pubmed = {1650231}, Title = {Sparing of function after neonatal frontal lesions correlates with increased cortical dendritic branching: a possible mechanism for the Kennard effect}, Uuid = {3F8104D4-5411-4513-9BD3-F451714EDEF2}, Volume = {43}, Year = {1991}} @article{Kolb:1996, Abstract = {Rats with removal of the medial prefrontal (mPFC) cortex at days 3, 6, 9, 15, or 30 were compared behaviourally and anatomically to littermate controls. In contrast to adult operates, mPFC lesions at all young ages led to the development of an abnormally thin cortical mantle. In addition, although there was an obvious cavity in brains examined in the early postoperative period, the brains of animals with lesions at day 9 or 15 had no lesion cavity in adulthood as part of the cortex appeared to regrow. The differential anatomical consequences of the lesions at days 9 and 15 was correlated with a differential behavioural outcome as well. Thus although rats in all young lesion groups showed a milder behavioural syndrome than rats with comparable lesions in adulthood, the functional outcome was best for animals with lesions at 9 days of age.}, Author = {Kolb, B. and Petrie, B. and Cioe, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Behav Brain Res}, Keywords = {Foot/anatomy &histology;Body Weight/physiology;Rats;Behavior, Animal/*physiology;Female;Comparative Study;Prefrontal Cortex/growth &development/*injuries/pathology;Maze Learning/physiology;Animal;D-4;Aging/*physiology;Animals, Newborn;Support, Non-U.S. Gov't;Organ Weight/physiology;Male;Movement/physiology;Feeding Behavior/physiology}, Number = {1-2}, Organization = {Department of Psychology, University of Lethbridge, Canada. kolb\@hg.uleth.ca}, Pages = {1-14.}, Title = {Recovery from early cortical damage in rats, VII. Comparison of the behavioural and anatomical effects of medial prefrontal lesions at different ages of neural maturation}, Uuid = {87B3E229-D23B-11D9-B244-000D9346EC2A}, Volume = {79}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8883811}} @article{Kolb:1997, Abstract = {Rats were given medial frontal lesions at 7 days of age and were tested as adults on tests of forelimb use, forelimb tactile sensitivity, tongue use, hindleg use, and in a spatial navigation task. The brains were processed with a modified Golgi-Cox procedure and dendritic arborization and spine density was measured. The animals showed recovery only on the spatial task and this was associated with an increase in the number of spines per unit length of dendrite. We also reanalyzed Golgi-Cox stained material from an experiment in which animals were depleted of cortical noradrenaline (NA) in infancy and then given frontal lesions on day 7. The NA depletion blocked the recovery from frontal lesions. Analysis of dendritic morphology showed that in otherwise intact rats, NA depletion decreased dendritic arbor but increased spine density to the level of frontal operates. Depleted frontal-operates showed no additional increase in spine density and also showed a decrease in dendritic arborization. These results suggest that recovery from neonatal cortical injury and from neonatal noradrenaline depletion may be supported by changes in both the dendritic arborization and the spine density in the remaining cortex.}, Author = {Kolb, B. and Stewart, J. and Sutherland, R. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {Tongue;Touch;Musculoskeletal Equilibrium;Animals;Frontal Lobe;Rats;Norepinephrine;Forelimb;Neurites;Sympatholytics;Pyramidal Cells;Male;Sympathectomy, Chemical;Body Weight;Animals, Newborn;Organ Size;Maze Learning;24 Pubmed search results 2008;Oxidopamine;Research Support, Non-U.S. Gov't}, Medline = {98133762}, Month = {12}, Nlm_Id = {8004872}, Number = {1-2}, Organization = {Department of Psychology, University of Lethbridge, AB, Canada. Kolb\@HG.ULETH.CA}, Pages = {61-70}, Pubmed = {9475615}, Title = {Recovery of function is associated with increased spine density in cortical pyramidal cells after frontal lesions and/or noradrenaline depletion in neonatal rats}, Uuid = {5DF92B5B-920F-4E25-B133-F3EC9A6DEA95}, Volume = {89}, Year = {1997}} @article{Kolb:1998, Abstract = {Rats were given suction lesions of the presumptive frontal cortex on embryonic day 18 (E18) and subsequently tested, as adults, on tests of spatial navigation (Morris water task, radial arm maze), motor tasks (Whishaw reaching task, beam walking), and locomotor activity. Frontal cortical lesions at E18 affected cerebral morphogenesis, producing unusual morphological structures including abnormal patches of neurons in the cortex and white matter as well as neuronal bridges between the hemispheres. A small sample of E18 operates also had hydrocephaly. The animals with E18 lesions without hydrocephalus were behaviorally indistinguishable from littermate controls. The results demonstrate that animals with focal lesions of the presumptive frontal cortex have gross abnormalities in cerebral morphology but the lesions leave the functions normally subserved by the frontal cortex in adult rats unaffected. The results are discussed in the context of a hypothesis regarding the optimal times for functional recovery from cortical injury.}, Author = {Kolb, B. and Cioe, J. and Muirhead, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Movement;Hindlimb;Touch;Musculoskeletal Equilibrium;Female;Rats;Organ Size;Motor Activity;Animals, Newborn;Maze Learning;Pregnancy;Animals;Cerebral Cortex;24 Pubmed search results 2008;Frontal Lobe}, Medline = {98237558}, Month = {3}, Nlm_Id = {8004872}, Number = {1-2}, Organization = {Department of Psychology, University of Lethbridge, Canada. Kolb\@HG.ULETH.CA}, Pages = {143-55}, Pubmed = {9578447}, Title = {Cerebral morphology and functional sparing after prenatal frontal cortex lesions in rats}, Uuid = {00B97F60-6778-4654-839F-A64844F9E93D}, Volume = {91}, Year = {1998}} @article{Kolb:1998a, Abstract = {The experiments described here show that the cavity left by midline frontal cortex removals at 10 days of age (P10) fills in with neural tissue. Similar changes are not found at earlier and later ages. This neuronal filling is blocked by prior pretreatment by administration of Bromodeoxyuridine (BrdU) on embryonic day 13. Administration of BrdU following the P10 lesion does not interfere with regrowth. Subsequent immunohistochemical staining for BrdU demonstrates the regrown area to be composed of newly generated cells. which include pyramidal and nonpyramidal neurons. Injections of a retrograde tracer into the striatum or posterior parietal cortex shows that the new neurons have connections similar to those of undamaged brains. The regrowth of this tissue is correlated with recovery of function in a test of forelimb use. Thus, the mammalian brain, during some privileged postnatal stages of growth. is capable of extensive reorganization that includes regeneration of lost neurons. These results are discussed in relation to the proximity of the lesion to the stem cells in the lateral ventricle and their postnatal migrational activities. 98237557 0166-4328 Journal Article}, Author = {Kolb, B. and Gibb, R. and Gorny, G. and Whishaw, I. Q.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {Movement;Animals;Nerve Regeneration/*physiology;Frontal Lobe;Rats;Neural Pathways;Mitosis;Mitosis/physiology;Frontal Lobe/cytology/pathology/*physiology;Female;D both;Animal;Movement/physiology;Antimetabolites;Male;Antimetabolites/diagnostic use;Nerve Regeneration;Animals, Newborn;Support, Non-U.S. Gov't;Neural Pathways/cytology/pathology/physiology;Animals, Newborn/*physiology;Neurons;Fluorescent Antibody Technique, Direct;Immunohistochemistry;Bromodeoxyuridine/diagnostic use;Bromodeoxyuridine;Neurons/physiology;Research Support, Non-U.S. Gov't}, Medline = {98237557}, Month = {3}, Nlm_Id = {8004872}, Number = {1-2}, Organization = {Department of Psychology, University of Lethbridge, Canada. Kolb\@HG.ULETH.CA}, Pages = {127-41}, Pubmed = {9578446}, Title = {Possible regeneration of rat medial frontal cortex following neonatal frontal lesions}, Uuid = {87B3E640-D23B-11D9-B244-000D9346EC2A}, Volume = {91}, Year = {1998}, url = {papers/Kolb_BehavBrainRes1998.pdf}} @article{Kolb:2003, Abstract = {Rats were given lesions of the temporal association cortex on postnatal day 4 or 10, or in adulthood. Ninety days later they were trained on two visual tasks (visual-spatial navigation; horizontal-vertical stripes discrimination). Lesion animals were compared behaviorally and neuroanatomically to littermate sham control rats. The day 4 lesions produced a larger deficit in the navigation task than day 10 or adult lesions. There were no deficits in the discrimination task. Analysis of the brains showed that the day 4 lesions produced a smaller brain and thinner cortex than day 10 lesions. The day 10 lesions produced hypertrophy in the dendritic arborization of pyramidal cells in parietal cortex. The results are consistent with the general findings that perinatal cortical injury in rats produces more severe behavioral and morphological effects than similar lesions in the second week of life and that cortical lesions around day 10 lead to an increase in cortical synaptogenesis.}, Author = {Kolb, Bryan and Cioe, Jan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0166-4328}, Journal = {Behav Brain Res}, Keywords = {Motor Activity;Rats, Long-Evans;Animals;Aging;Rats;Comparative Study;Space Perception;Brain;Sex;Female;Reaction Time;Orientation;Time Factors;Dendrites;Nerve Regeneration;Body Weight;Animals, Newborn;Escape Reaction;Male;Discrimination Learning;Behavior, Animal;Organ Size;Psychomotor Performance;Temporal Lobe;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {22827283}, Month = {9}, Nlm_Id = {8004872}, Number = {1-2}, Organization = {Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, Alta., Canada T1K 3M4. kolb\@uleth.ca}, Pages = {67-76}, Pii = {S0166432803000688}, Pubmed = {12946596}, Title = {Recovery from early cortical damage in rats. IX. Differential behavioral and anatomical effects of temporal cortex lesions at different ages of neural maturation}, Uuid = {06B5E91B-6EE2-411C-A89F-9B719DF34A08}, Volume = {144}, Year = {2003}} @article{Kolb:1985, Abstract = {Syrian golden hamsters with removals of the medial or ventral subfields of the frontal cortex at 4 days of age were compared behaviorally and neuroanatomically with hamsters with similar removals in adulthood. The behavioral results showed that hamsters with neonatal lesions show little sparing of species-typical behaviors such as hoarding and nest building. Study of the development of animals with early lesions showed that although as young juveniles the operated hamsters did not appear to be different from their littermate controls, as they developed they failed to improve in their performance as their littermates did. As adults these early operates were thus severely impaired relative to their littermates. Nonetheless, under certain environmental conditions it was possible to show that the animals were capable of performing the behaviors nearly as proficiently as normal animals. Thus, in order to thoroughly assess the extent of behavioral sparing following early neonatal lesions, it is necessary to test animals under widely varying stimulus conditions. Finally, when the brains of neonatally operated hamsters were compared with those of animals operated on in adulthood, there were striking differences; although the area of cavity appeared smaller in the neonatal operates, their brains weighed less and the remaining neocortex was thinner.}, Author = {Kolb, B. and Whishaw, I. Q.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0735-7044}, Journal = {Behav Neurosci}, Keywords = {Brain;Cerebral Cortex;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Species Specificity;Behavior, Animal;Organ Size;Mesocricetus;Nesting Behavior;Animals, Newborn;Animals;Male;Hamsters;Feeding Behavior;Frontal Lobe}, Medline = {87298932}, Month = {8}, Nlm_Id = {8302411}, Number = {4}, Pages = {691-706}, Pubmed = {3843735}, Title = {Neonatal frontal lesions in hamsters impair species-typical behaviors and reduce brain weight and neocortical thickness}, Uuid = {33C4AEE3-AB7B-40ED-9D3F-3721256842A6}, Volume = {99}, Year = {1985}} @article{Kolb:1993, Abstract = {Rats given medial frontal lesions on Postnatal Day 1 or Day 10 were trained on the Morris water task on Days 19-21 or Days 56-58. The operated groups were equally impaired at the water task on Days 19-21, but the Day 10 rats had recovered by 56 days. Dendritic arborization and spine density were analyzed in parietal layer II-III pyramidal cells. At Day 60, but not at Day 22, the Day 10 animals had more dendritic spines per unit dendritic length than did the controls or Day 1 rats. Thus, there was functional recovery rather than sparing after frontal lesions at 10 days, and the recovery was correlated with an increase in dendritic spines.}, Author = {Kolb, B. and Gibb, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0735-7044}, Journal = {Behav Neurosci}, Keywords = {Escape Reaction;24 Pubmed search results 2008;Dendrites;Research Support, Non-U.S. Gov't;Orientation;Nerve Regeneration;Female;Mental Recall;Neuronal Plasticity;Rats;Organ Size;Brain Mapping;Male;Age Factors;Animals;Neurons;Frontal Lobe}, Medline = {94107488}, Month = {10}, Nlm_Id = {8302411}, Number = {5}, Organization = {Department of Psychology, University of Lethbridge, Alberta, Canada.}, Pages = {799-811}, Pubmed = {8280389}, Title = {Possible anatomical basis of recovery of function after neonatal frontal lesions in rats}, Uuid = {680B3703-7CE9-4BFE-89C0-F4966F6AA21C}, Volume = {107}, Year = {1993}} @article{Kolb:2004, Abstract = {We compare the effects of psychoactive drugs such as morphine and amphetamine on the synaptic organization of neurons in the orbital frontal (OFC) and medial frontal (mPFC) regions in the rat. Both regions are altered chronically by exposure to intermittent doses of either drug but the effects are area-dependent. For example, whereas morphine produces increased spine density in OFC but decreased spine density in mPFC. The differential response of the OFC and mPFC to drugs is paralleled by an areal-dependent effect of gonadal hormones on these regions as well: males have greater dendritic arborization in the mPFC whereas females have a greater arborization in the OFC. We also compared the effects of neonatal injury to the OFC and mPFC on cognitive, motor, and social behaviors as well as on the anatomical organization of the remaining brain. Again, there were differential effects of the treatments to the OFC and mPFC. Neonatal OFC lesions allowed virtually complete functional recovery of cognitive and motor behaviors, which was correlated with mild abnormalities in cerebral development compared to the more severe deficits and morphological sequelae following mPFC lesions at the same ages. One exception was the effect of OFC on social behavior, which was severe regardless of whether the injury was in infancy or adulthood. It is proposed that both drug-induced and developmental abnormalities in the integrity of OFC neurons may lead to deficits in social behavior or other behavioral pathologies, possibly including depression.}, Author = {Kolb, Bryan and Pellis, Sergio and Robinson, Terry E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0278-2626}, Journal = {Brain Cogn}, Keywords = {Neurons;Central Nervous System Stimulants;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Rats;Neuronal Plasticity;Research Support, U.S. Gov't, P.H.S.;Gonadal Steroid Hormones;Prefrontal Cortex;review, tutorial;Nerve Net;Animals;Orbit;review;Frontal Lobe}, Month = {6}, Nlm_Id = {8218014}, Number = {1}, Organization = {Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge, AB, Canada T1K 3M4. kolb\@uleth.ca}, Pages = {104-15}, Pii = {S0278262603002781}, Pubmed = {15134846}, Title = {Plasticity and functions of the orbital frontal cortex}, Uuid = {55F42FB7-BF07-4D88-8B05-DD17DE8EA895}, Volume = {55}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0278-2626(03)00278-1}} @article{Kolb:1994, Abstract = {Rats were given frontal cortical lesions at day 1 or 10 of life. Later, as adults, they were either: (1) processed with Golgi-Cox in order to analyze cortical dendritic arborization; (2) given injections of True Blue into the parietal or visual cortex, or (3) given injections of [3H]leucine into the substantia nigra. An additional group of normal rats were given injections of fluorescent dyes into the cortex on day 4 or 10 of life. The main findings were that (1) adult hemispheres with day 10 lesions had greater dendritic arbor than normal hemispheres, (2) adult hemispheres with day 1 lesions had reduced dendritic branching relative to normal hemispheres, (3) adult rats with day 10 lesions had no obvious abnormalities in cortical connections, (4) adult rats with day 1 lesions had abnormal thalamo-cortical, amygdalo-cortical, and nigro-cortical connections, and (5) many of these abnormal connections were present in the brains of 4-day-old normal rats. Since the 'abnormal' connections in the very early frontal operates were present in day 4 animals, it appears that they result from the failure of exuberant connections to retract after the lesions. The increased dendritic growth in day 10 operates does not appear related to qualitative changes in cortical afferents or efferents and may related to increased intrinsic cortical connectivity. Since rats with day 10 lesions have previously been shown to exhibit significant recovery of function, it is possible that the increased dendritic arborization is supporting the functional restitution.}, Author = {Kolb, B. and Gibb, R. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Visual Cortex;Aging;Brain Diseases;Research Support, Non-U.S. Gov't;Dendrites;Reference Values;Rats;Neural Pathways;Fluorescent Dyes;Benzofurans;Parietal Lobe;Animals, Newborn;Animals;Injections;Rats, Inbred Strains;Male;Frontal Lobe}, Medline = {94340407}, Month = {5}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Department of Psychology, University of Lethbridge, Alta., Canada.}, Pages = {85-97}, Pubmed = {8062102}, Title = {Neonatal frontal cortical lesions in rats alter cortical structure and connectivity}, Uuid = {BAA1CDEB-C26D-11DA-969D-000D9346EC2A}, Volume = {645}, Year = {1994}} @article{Kolb:1994a, Abstract = {Following bilateral removal of the medial frontal cortex, which included the medial prefrontal and adjacent midline motor cortex, 4-day-old rats were given transplants of embryonic day 17 frontal cortical tissue. Other rats were given only frontal lesions or sham operations. In adulthood, the animals were trained on a spatial navigation task and a forelimb reaching task. The transplanted tissue grew well and interacted morphologically with the host but the grafts failed to reduce the spatial navigation and motor deficits resulting from the frontal removals. The grafts also failed to reduce the anatomical sequelae of the early lesions, which included cortical thinning and thalamic shrinkage. It appears unlikely that cortical transplantation will be a viable treatment for recovery from perinatal frontal cortical injury.}, Author = {Kolb, B. and Muirhead, D. and Cioe, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Behavior, Animal;Rats;Space Perception;Psychomotor Performance;Grooming;Body Weight;Organ Size;Animals, Newborn;Motor Activity;Forelimb;Animals;Brain;Rats, Inbred Strains;Fetal Tissue Transplantation;Frontal Lobe}, Medline = {94349121}, Month = {5}, Nlm_Id = {0045503}, Number = {1}, Organization = {University of Lethbridge, AB, Canada.}, Pages = {15-22}, Pubmed = {8069698}, Title = {Neonatal frontal cortex grafts fail to attenuate behavioural deficits or abnormal cortical morphogenesis}, Uuid = {6E186ED3-A3A9-4976-A027-0856BFE0E4FE}, Volume = {647}, Year = {1994}} @article{Kolb:2000, Abstract = {Rats were given bilateral lesions of the motor cortex on the day of birth (P1), tenth day of life (P10), or in adulthood. They were trained on several motor tasks (skilled forelimb reaching, beam traversing, tongue extension), general motor activity, and a test of spatial learning (Morris water task). Although all lesion groups were impaired at skilled reaching, the P10 group was less impaired than either of the other two lesion groups. Furthermore, on the other motor tests the P10 group did not differ from controls whereas both P1 and adult groups were impaired. Only the P1 lesion group was impaired at the acquisition of the Morris water task. Anatomical analyses revealed that the P1 and P10 rats had smaller brains than the other two groups as well as having a generalized decrease in cortical thickness. Dendritic analysis of layer III pyramidal cells in the parietal cortex revealed a decrease in apical arbor in the lesion groups and an increase in the basilar arbor of the P1 and adult lesion animals. The P1 and adult operated groups showed an increase in spine density in the basilar dendrites of layer V pyramidal cells. Finally, analysis of the pattern of corticospinal projections revealed that the P1 animals had a markedly wider field of corticospinal projection neurons than any of the other groups. The widespread anatomical changes in all lesion groups versus the relatively better behavioral recovery after P10 lesions suggests that day 10 represents an optimal period for adapting to brain damage and subsequent brain reorganization.}, Author = {Kolb, B. and Cioe, J. and Whishaw, I. Q.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Dendrites;Motor Skills;Motor Cortex;Rats, Long-Evans;Rats;Female;Animals, Newborn;Motor Activity;Maze Learning;Animals;Parietal Lobe;Male;Age Factors;24 Pubmed search results 2008}, Medline = {20511893}, Month = {11}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Department of Psychology and Neuroscience, University of Lethbridge, AB T1K 3M4, Lethbridge, Canada. kolb\@uleth.ca}, Pages = {62-74}, Pii = {S0006899300028286}, Pubmed = {11056185}, Title = {Is there an optimal age for recovery from motor cortex lesions? I. Behavioral and anatomical sequelae of bilateral motor cortex lesions in rats on postnatal days 1, 10, and in adulthood}, Uuid = {62EBC92E-F85F-4BFA-A64E-1183BC3077C2}, Volume = {882}, Year = {2000}} @article{Kolb:1999, Abstract = {The mitotic marker 5-bromodeoxyuridine (BrdU) was injected twice daily (60 mg/kg) into pregnant hooded rats on one of embryonic days (E) 11, 12, 13, 15, 17, or 21, or into rat pups on postnatal day (P) 10. The principal findings were the following: (1) BrdU exposure on E11 produces profound effects on body morphology, and animals must be fed a special diet because of chronic tooth abnormalities; (2) BrdU exposure at E17 or earlier produces a change in coat spotting pattern, the precise pattern varying with age; (3) BrdU exposure on E15 or earlier produces a reduction in both brain and body weight; (4) BrdU exposure on E17 or earlier reduces cortical thickness; (5) BrdU exposure on E11-E13 and at P10 reduces cerebellar size relative to cerebral size; (6) spatial learning is significantly affected after injections of BrdU at E11-E17, but the largest effect is on E17; (7) the deficit in spatial learning may be related in part to a reduction in visual acuity; and (8) skilled forelimb ability is most disrupted after BrdU exposure at E15 but is also impaired after injections on E13 or earlier. BrdU thus has teratological effects on body, brain, and behavior that vary with the developmental age of the fetus or infant.}, Author = {Kolb, B. and Pedersen, B. and Ballermann, M. and Gibb, R. and Whishaw, I. Q.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Embryo;Aging;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Behavior, Animal;Behavioral Symptoms;Rats, Long-Evans;Rats;Abnormalities, Drug-Induced;Animals, Newborn;Drug Administration Schedule;Brain;Bromodeoxyuridine;Injections;Animals}, Medline = {99165835}, Month = {3}, Nlm_Id = {8102140}, Number = {6}, Organization = {Department of Psychology and Neuroscience, University of Lethbridge, Lethbridge, Canada T1K 3M4.}, Pages = {2337-46}, Pubmed = {10066283}, Title = {Embryonic and postnatal injections of bromodeoxyuridine produce age-dependent morphological and behavioral abnormalities}, Uuid = {17BC6A1F-5DDD-4A53-B5B1-988421F95431}, Volume = {19}, Year = {1999}} @article{Kolb:2000a, Abstract = {The size of cortical removal was varied in rats that were given medial frontal lesions on postnatal day 2. In adulthood, the animals were trained on the Morris water task and Whishaw reaching task following which the brains were harvested and dendritic arborization and spine density was examined in the layer III pyramidal cells in Zilles' area Par1. There was a small relationship between lesion size and behavioral outcome as smaller lesions produced somewhat smaller deficits. In contrast, both small and large lesions produced large reductions in brain weight, dendritic arborization, and spine density. The cortex of newborn rats appears to be especially vulnerable to even restricted injury. This contrasts to the effects of similar injury a week later when animals show extensive functional recovery and anatomical compensation.}, Author = {Kolb, B. and Cioe, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0028-3908}, Journal = {Neuropharmacology}, Keywords = {Research Support, Non-U.S. Gov't;Rats, Long-Evans;Animals;Frontal Lobe;Rats;Neuronal Plasticity;Appetitive Behavior;Female;Cell Count;Reaction Time;Male;Dendrites;Analysis of Variance;Animals, Newborn;Brain Injuries;Organ Size;Maze Learning;24 Pubmed search results 2008;Cerebral Decortication;Swimming}, Medline = {20164901}, Month = {3}, Nlm_Id = {0236217}, Number = {5}, Organization = {Department of Psychology and Neuroscience, University of Lethbridge, Lethbridge, Canada. kolb\@hg.uleth.ca}, Pages = {756-64}, Pii = {S0028390899002609}, Pubmed = {10699442}, Title = {Recovery from early cortical damage in rats, VIII. Earlier may be worse: behavioural dysfunction and abnormal cerebral morphogenesis following perinatal frontal cortical lesions in the rat}, Uuid = {784BFBB2-472A-4946-87CE-1A4D81712C0A}, Volume = {39}, Year = {2000}} @article{Kole:2008, Abstract = {The axon initial segment (AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium (Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel density at the AIS is similar to that at the soma and proximal dendrites. Here we provide data obtained by antibody staining, whole-cell voltage-clamp and Na(+) imaging, together with modeling, which indicate that the Na(+) channel density at the AIS of cortical pyramidal neurons is approximately 50 times that in the proximal dendrites. Anchoring of Na(+) channels to the cytoskeleton can explain this discrepancy, as disruption of the actin cytoskeleton increased the Na(+) current measured in patches from the AIS. Computational models required a high Na(+) channel density ( approximately 2,500 pS mum(-2)) at the AIS to account for observations on action potential generation and backpropagation. In conclusion, action potential generation requires a high Na(+) channel density at the AIS, which is maintained by tight anchoring to the actin cytoskeleton.}, Author = {Kole, Maarten H. P. and Ilschner, Susanne U. and Kampa, Bj{\"o}rn M. and Williams, Stephen R. and Ruben, Peter C. and Stuart, Greg J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9809671}, Number = {2}, Organization = {Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Garran Road, Canberra ACT 0200, Australia.}, Pages = {178-86}, Pii = {nn2040}, Pubmed = {18204443}, Title = {Action potential generation requires a high sodium channel density in the axon initial segment}, Uuid = {88E60543-0419-4F29-B068-20AD3941DF52}, Volume = {11}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn2040}} @article{Koliatsos:1994, Abstract = {The present study proposes a reproducible model of experimental degeneration of adult motor neurons in the rat. Avulsion of ventral roots in the adult lumbar cord transects motor axons at the root exit and leads to retrograde cell death of 80\%of motor neurons 2 weeks later; this result follows a series of retrograde changes, including chromatolysis, loss of transmitter phenotype, and accumulation of phosphorylated neurofilaments in perikarya. Glial cells recruited at the site of retrograde injury express both microglia-specific epitopes (as exemplified by OX-42 immunoreactivity) and macrophage-specific markers (e.g., ED-1 immunoreactivity). Macrophage-specific markers become particularly intense 7 days postaxotomy and provide additional evidence of active phagocytosis of injured neurons. Ventral root avulsion is a very useful model for assessing mechanisms of motor neuron death and testing the ability of trophic factors and other agents to preserve the phenotype and promote the survival of adult motor neurons in vivo.}, Author = {Koliatsos, V. E. and Price, W. L. and Pardo, C. A. and Price, D. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Fluorescent Dyes;Animals;Rats;Phenotype;Models, Biological;Neurons, Afferent;Rats, Sprague-Dawley;Sciatic Nerve;Axons;Not relevant;Choline O-Acetyltransferase;11 Glia;Spinal Nerve Roots;Stilbamidines;Male;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Motor Neurons;Immunohistochemistry;Retrograde Degeneration}, Medline = {94267079}, Month = {4}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2196.}, Pages = {35-44}, Pubmed = {8207127}, Title = {Ventral root avulsion: an experimental model of death of adult motor neurons}, Uuid = {72B75CF9-7D3C-44AD-8898-01AC571137B1}, Volume = {342}, Year = {1994}} @article{Komai:2006, Abstract = {Sensory experience is necessary for normal cortical development. This has been shown by sensory deprivation and pharmacological perturbation of the cortex. Because these manipulations affect the cortical network as a whole, the role of postsynaptic cellular properties during experience-dependent development is unclear. Here we addressed the developmental role of somatodendritic excitability, which enables postsynaptic spike timing-dependent forms of plasticity, in rat somatosensory cortex. We used short interfering RNA (siRNA)-based knockdown of Na+ channels to suppress the somatodendritic excitability of small numbers of layer 2/3 pyramidal neurons in the barrel cortex, without altering the ascending sensory pathway. In vivo recordings from siRNA-expressing cells revealed that this manipulation interfered with the normal developmental strengthening of sensory responses. The sensory responsiveness of neighboring cortical neurons was unchanged, indicating that the cortical network was unchanged. We conclude that somatodendritic excitability of the postsynaptic neuron is needed for the regulation of synaptic strength in the developing sensory cortex.}, Author = {Komai, Shoji and Licznerski, Pawel and Cetin, Ali and Waters, Jack and Denk, Winfried and Brecht, Michael and Osten, Pavel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Animals;Rats;Sodium Channels;Microscopy, Confocal;Neuronal Plasticity;Synaptic Transmission;Lentivirus;Sensory Deprivation;RNA Interference;Rats, Wistar;Pyramidal Cells;Green Fluorescent Proteins;RNA, Small Interfering;research support, non-u.s. gov't ;DNA, Recombinant;21 Neurophysiology;Somatosensory Cortex;24 Pubmed search results 2008;Excitatory Postsynaptic Potentials}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Department of Biomedical Optics, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.}, Pages = {1125-33}, Pii = {nn1752}, Pubmed = {16921372}, Title = {Postsynaptic excitability is necessary for strengthening of cortical sensory responses during experience-dependent development}, Uuid = {F78B5867-D7E5-48F0-9277-940E06E290A5}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1752}} @article{Komitova:2006, Abstract = {Environmental enrichment (EE) alleviates sensorimotor deficits after brain infarcts but the cellular correlates are not well-known. This study aimed to test the effects of postischemic EE on neocortical cell genesis. A neocortical infarct was caused by distal ligation of the middle cerebral artery in adult spontaneously hypertensive rats, subsequently housed in standard environment or EE. Bromodeoxyuridine (BrdU) was administered during the first postischemic week to label proliferating cells and BrdU incorporation was quantified 4 weeks later in the periinfarct, ipsilateral medial and contralateral cortex. Immunohistochemistry and confocal microscopy were used to analyze co-localization of BrdU with neuronal (calbindin D28k, calretinin, parvalbumin, glutamic acid decarboxylase, tyrosine hydroxylase), astrocytic (glial fibrillary acidic protein, glutamine synthetase, vimentin, nestin), microglia/macrophage (CD11b/Ox-42, CD68/ED-1), oligodendrocyte progenitor/polydendrocyte (NG2, platelet-derived growth factor alpha receptor) or mature oligodendrocyte (myelin basic protein) markers. BrdU positive cells were increased in all analyzed cortical regions in stroke EE rats compared with stroke standard environment rats. Newly born cells in the periinfarct cortex were mostly reactive astroglia. Occasionally, BrdU positive cells in the periinfarct cortex that were negative for glial or microglia/macrophage markers co-expressed markers typical for interneurons but did not express appropriate functional markers. The majority of BrdU positive cells in intact cortical regions, ipsi- and contralaterally, were identified as NG2 positive polydendrocytes. Perineuronally situated newly born cells and polydendrocytes were found to be brain-derived neurotrophic factor immunoreactive. In conclusion, EE enhanced newborn glial scar astroglia and NG2+ polydendrocytes in the postischemic neocortex which might be beneficial for brain repair and poststroke plasticity.}, Author = {Komitova, and Perfilieva, and Mattsson, and Eriksson, and Johansson,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {06 Adult neurogenesis injury induced;11 Glia}, Month = {1}, Nlm_Id = {0370712}, Organization = {The Arvid Carlsson Institute for Neuroscience at the Institute of Clinical Neuroscience, G{\"o}teborg University, G{\"o}teborg, Sweden.}, Pii = {S0014-4886(05)00461-9}, Pubmed = {16427625}, Title = {Enriched environment after focal cortical ischemia enhances the generation of astroglia and NG2 positive polydendrocytes in adult rat neocortex}, Uuid = {2AC7FE11-1C83-45C7-883A-6FA9E9981700}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2005.12.007}} @article{Komitova:2002, Abstract = {The study aimed to elucidate the effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis. A cortical infarct was induced by a permanent ligation of the middle cerebral artery distal to the striatal branches in 6-month-old spontaneously hypertensive rats. Bromodeoxyuridine (BrdU) was administered as 7 consecutive daily injections starting 24 hours after surgery and animals were housed in standard or enriched environment. Four weeks after completed BrdU administration, BrdU incorporation and its co-localization with the neuronal markers NeuN and calbindin D28k, and the astrocytic marker glial fibrillary acidic protein in the granular cell layer and subgranular zone of the hippocampal dentate gyrus were determined with immunohistochemistry and were quantified stereologically. Compared with sham-operated rats, rats with cortical infarcts had a five-to sixfold ipsilateral increase in BrdU-labeled cells. About 80\%of the new cells were neurons. Differential postischemic housing did not influence significantly the total number of surviving BrdU-labeled cells or newborn neurons. However, postischemic environmental enrichment increased the ipsilateral generation of astrocytes normalizing the astrocyte-to-neuron ratio, which was significantly reduced in rats housed in standard environment postischemically. 0271-678x Journal Article}, Author = {Komitova, M. and Perfilieva, E. and Mattsson, B. and Eriksson, P. S. and Johansson, B. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {J Cereb Blood Flow Metab}, Keywords = {Animals;Rats;*Cell Differentiation;Brain Ischemia/*pathology;Astrocytes/chemistry/pathology;Phenotype;Hippocampus/*pathology;Brain Infarction/pathology;Bromodeoxyuridine/analysis/metabolism;Glial Fibrillary Acidic Protein/analysis;Fluorescent Antibody Technique;Rats, Inbred SHR;Male;Support, Non-U.S. Gov't;D abstr;Neurons/chemistry/pathology;Calcium-Binding Protein, Vitamin D-Dependent/analysis;Animals, Newborn;06 Adult neurogenesis injury induced;Immunohistochemistry;Biological Markers/analysis}, Number = {7}, Organization = {Institute of Clinical Neuroscience, University of Goteborg, Sweden.}, Pages = {852-60}, Pubmed = {12142570}, Title = {Effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis and differentiation in the adult rat}, Uuid = {8B9D204E-EC81-11DA-8605-000D9346EC2A}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12142570}} @article{Kondo:2004, Abstract = {Cell-cell fusion generates multinucleated cells such as osteoclasts in bone, myotubes in muscle, and trophoblasts in placenta. Molecular details governing these fusion processes are still largely unknown. As a step toward identification of fusogenic genes, we tested the concept that retroviral vectors can be packaged as a result of cell-cell fusion. First, we introduced replication-deficient retroviral vectors expressing mCAT-1, which mediates fusogenic interaction with the retroviral envelope protein Env, into Chinese hamster ovary (CHO) cells to generate vector cells. Plasmids expressing virion proteins Gag, Pol, and Env were introduced into a separate culture of CHO cells to generate packaging cells. Co-culturing vector and packaging cells resulted in production of infectious retroviruses carrying the mCAT-1 gene as a consequence of cell-cell fusion. Second, we introduced a retroviral vector into primary osteoclast precursors and co-cultured them with established osteoclast precursor RAW264.7 cells, which turned out to harbor packaging activity. Packaged retroviral vector was detected in culture supernatants only where the osteoclast differentiation factor receptor activator for NF-kappaB ligand (RANKL) induced fusion between these two cell types. These data suggest that retrovirus production can occur as a result of cell-cell fusion. This provides a novel approach for isolating and characterizing fusogenic genes using retroviral expression vectors.}, Author = {Kondo, Takako and Ikeda, Kyoji and Matsuo, Koichi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {8756-3282}, Journal = {Bone}, Keywords = {Hamsters;Gene Products, env;Animals;Trans-Activators;Carrier Proteins;Macrophages;Transfection;CHO Cells;Virus Assembly;Cell Fusion;Cell Line, Tumor;Cationic Amino Acid Transporter 1;Retroviridae;Giant Cells;11 Glia;Gene Products, gag;Genetic Vectors;Cricetulus;Membrane Glycoproteins;Mice;Gene Expression;Gene Products, pol;Osteoclasts;Research Support, Non-U.S. Gov't}, Month = {11}, Nlm_Id = {8504048}, Number = {5}, Organization = {Department of Geriatric Research, National Institute for Longevity Sciences (NILS), Aichi 474-8522, Japan.}, Pages = {1120-6}, Pii = {S8756-3282(04)00263-7}, Pubmed = {15542037}, Title = {Detection of osteoclastic cell-cell fusion through retroviral vector packaging}, Uuid = {EB5B06AB-70FD-44A1-8F0A-2E0C20B087BC}, Volume = {35}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.bone.2004.06.011}} @article{Kondo:2001, Abstract = {PURPOSE: Cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The mechanisms of CD-induced epileptogenicity remain unknown. The difficulty in obtaining and testing human tissue warrants the identification and characterization of animal model(s) of CD that share most of the clinical, electroencephalographic (EEG), and histopathologic characteristics of human CD. In this study, we report on the in vivo EEG characterization of the radiation-induced model of CD. METHODS: Timed-pregnant Sprague-Dawley rats were irradiated on E17 using a single dose of 145 cGy or left untreated. Their litters were identified and implanted with bifrontal epidural and hippocampal depth electrodes for prolonged continuous EEG recordings. After prolonged EEG monitoring, animals were killed and their brains sectioned and stained for histologic studies. RESULTS: In utero-irradiated rats showed frequent spontaneous interictal epileptiform spikes and spontaneous seizures arising independently from the hippocampal or the frontal neocortical structures. No epileptiform or seizure activities were recorded from age-matched control rats. Histologic studies showed the presence of multiple cortical areas of neuronal clustering and disorganization. Moreover, pyramidal cell dispersion was seen in the CA1>CA3 areas of the hippocampal formations. CONCLUSIONS: Our results further characterize the in vivo EEG characteristics of the in utero radiation model of CD using long-term EEG monitoring. This model may be used to study the molecular and cellular changes in epileptogenic CD and to test the efficacy of newer antiepileptic medications.}, Author = {Kondo, S. and Najm, I. and Kunieda, T. and Perryman, S. and Yacubova, K. and L{\"u}ders, H. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Cerebral Cortex;Epilepsies, Partial;Electroencephalography;Rats, Sprague-Dawley;24 Pubmed search results 2008;21 Neurophysiology;21 Epilepsy;Hippocampus;Female;Rats;Evoked Potentials;Pregnancy;Animals;Disease Models, Animal;Radiation Injuries, Experimental;Neurons;Frontal Lobe}, Medline = {21600859}, Month = {10}, Nlm_Id = {2983306R}, Number = {10}, Organization = {Section of Epilepsy, Department of Neurology, The Cleveland Clinic Foundation, Cleveland, Ohio 44195 USA.}, Pages = {1221-7}, Pii = {38300}, Pubmed = {11737155}, Title = {Electroencephalographic characterization of an adult rat model of radiation-induced cortical dysplasia}, Uuid = {FAAC8B58-0C2B-4F1A-B74D-9523014174C7}, Volume = {42}, Year = {2001}} @article{Kondo:2000, Abstract = {During animal development, cells become progressively more restricted in the cell types to which they can give rise. In the central nervous system (CNS), for example, multipotential stem cells produce various kinds of specified precursors that divide a limited number of times before they terminally differentiate into either neurons or glial cells. We show here that certain extracellular signals can induce oligodendrocyte precursor cells to revert to multipotential neural stem cells, which can self-renew and give rise to neurons and astrocytes, as well as to oligodendrocytes. Thus, these precursor cells have greater developmental potential than previously thought.}, Author = {Kondo, T. and Raff, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Science}, Keywords = {Platelet-Derived Growth Factor/pharmacology;Culture Media, Serum-Free;BB;Cells, Cultured;Rats;Isoenzymes/biosynthesis/genetics;*Cell Differentiation;Bone Morphogenetic Proteins/pharmacology;Stem Cells/chemistry/*cytology;Neurons/chemistry/*cytology;Animal;02 Adult neurogenesis migration;Astrocytes/chemistry/*cytology;Glial Fibrillary Acidic Protein/analysis;Oligodendroglia/chemistry/*cytology;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;Glutamate Decarboxylase/biosynthesis/genetics;Neurofilament Proteins/analysis/biosynthesis;Thyroid Hormones/pharmacology;Animals, Newborn;Fibroblast Growth Factor 2/pharmacology;Cell Culture;Galactosylceramides/analysis;Culture Media;Optic Nerve/cytology;Blood}, Number = {5485}, Organization = {Medical Research Council Developmental Neurobiology Programme, MRC Laboratory for Molecular Cell Biology and the Biology Department, University College London, London WC1E 6BT, UK. t.kondo\@ucl.ac.uk}, Pages = {1754-7.}, Title = {Oligodendrocyte precursor cells reprogrammed to become multipotential CNS stem cells}, Uuid = {AB3E29F3-954B-4EC7-835A-ACBC4DAC0CE7}, Volume = {289}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10976069}} @article{Kontani:2005, Abstract = {Cell-cell fusion initiates fertilization, sculpts tissues during animal development, reprograms stem cells to new differentiated states, and may be a key step in cancer progression. While cell fusion is tightly regulated, the mechanisms that limit fusion to appropriate partners are unknown. Here, we report that the fus-1 gene is essential to repress fusion of epidermal cells in C. elegans: in severe fus-1 mutants, all epidermal cells, except the lateral seam cells, inappropriately fuse into a single large syncytium. This hyperfusion requires EFF-1, an integral membrane protein essential for fusion of epidermal cells into discrete syncytia. FUS-1 is localized to the apical plasma membrane in all epidermal cells potentiated to undergo fusion, whereas it is virtually undetectable in nonfusing seam cells. fus-1 encodes the e subunit of the vacuolar H(+)-ATPase (V-ATPase), and loss of other V-ATPase subunits also causes widespread hyperfusion. These findings raise the possibility of manipulating cell fusion by altering V-ATPase activity.}, Author = {Kontani, Kenji and Moskowitz, Ivan P. G. and Rothman, Joel H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1534-5807}, Journal = {Dev Cell}, Keywords = {08 Aberrant cell cycle;11 Glia;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {101120028}, Number = {5}, Organization = {Department of MCD Biology, Neuroscience Research Institute, University of California, Santa Barbara, 93106, USA.}, Pages = {787-94}, Pii = {S1534-5807(05)00098-5}, Pubmed = {15866168}, Title = {Repression of cell-cell fusion by components of the C. elegans vacuolar ATPase complex}, Uuid = {67D614CF-8BE3-4F39-B4FA-1435169C5E14}, Volume = {8}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devcel.2005.02.018}} @article{Konur:2005, Abstract = {Dendrites serve a critical role in neuronal information processing as sites of synaptic integration. The morphological diversity of dendritic architecture reflects specialized strategies that neurons have evolved to detect and process incoming information. Recent observations suggest that calcium signals exert an important influence on neuronal morphology by regulating the growth and branching of dendrites and the formation of dendritic spines. Calcium signals appear to influence branch dynamics by affecting the cytoskeleton near the site of calcium entry, whereas calcium-dependent dendritic growth involves activation of a transcriptional program.}, Author = {Konur, Sila and Ghosh, Anirvan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Division of Biological Sciences, Neurobiology Section, University of California, San Diego, La Jolla, California 92093, USA.}, Pages = {401-5}, Pii = {S0896-6273(05)00358-2}, Pubmed = {15882639}, Title = {Calcium signaling and the control of dendritic development}, Uuid = {FCC30B04-DDF8-4B7B-ABE2-204584CCA767}, Volume = {46}, Year = {2005}, url = {papers/Konur_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.022}} @article{Kootstra:1999, Abstract = {Human immunodeficiency virus type 1 (HIV-1) is considered to infect nondividing cells because nuclear localization signals (NLS) in matrix (MA, p17(Gag)) and Vpr allow active nuclear transport of the preintegration complex. Previous studies demonstrated that HIV-1 reverse transcription is successful only in cells with proliferative potential, thus restricting HIV-1 replication to cycling cells. To sort out this apparent discrepancy we compared the phenotype of a chimeric HIV-1 variant lacking a functional Vpr and MA-NLS (R7. deltaVpr.deltaNLS), and previously described to lack replicative capacity in macrophages and growth-arrested cells, with a chimera lacking a functional Vpr (R7.deltaVpr). Both variants replicated efficiently in primary macrophages, with only minimal differences in the kinetics of reverse transcription, integration, or p24 production. In agreement with our previous observation, elongation of reverse transcription was restricted to the proliferating subpopulation of macrophages. Replication of R7.deltaVpr and R7.deltaVpr.deltaNLS could also be demonstrated in aphidicolin-treated macrophages, indicating efficient nuclear transport in G1/S phase-arrested cells. In conclusion, our results confirm the dependency of the process of HIV-1 reverse transcriptase on cell proliferation in primary macrophages and exclude an important role of MA-NLS and Vpr in macrophage infection.}, Author = {Kootstra, N. A. and Schuitemaker, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {Research Support, Non-U.S. Gov't;Viral Proteins;HIV-1;Cells, Cultured;Macrophages;Peptide Chain Elongation, Translational;Humans;Variation (Genetics);Phenotype;Gene Products, vpr;Cell Cycle;15 Retrovirus mechanism;Gene Products, gag;Kinetics;11 Glia;Mutagenesis;Nuclear Localization Signals;Nuclear Localization Signal;HIV Antigens;DNA, Viral;Cell Division;24 Pubmed search results 2008;Virus Replication;S Phase;Bromodeoxyuridine;Transcription, Genetic}, Medline = {99119491}, Month = {1}, Nlm_Id = {0110674}, Number = {2}, Organization = {Department of Clinical Viral-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Academic Medical Centre, University of Amsterdam, Plesmanlaan 125, Amsterdam, 1066 CX, The Netherlands.}, Pages = {170-80}, Pii = {S004268229899482X}, Pubmed = {9918876}, Title = {Phenotype of HIV-1 lacking a functional nuclear localization signal in matrix protein of gag and Vpr is comparable to wild-type HIV-1 in primary macrophages}, Uuid = {16440373-F916-4122-A16D-32602A6B2F20}, Volume = {253}, Year = {1999}} @article{Kopec:2000, Abstract = {Nitric oxide (NO) is produced by inducible nitric oxide synthase (iNOS) in activated microglia and has been shown to participate in host defense mechanisms. However, the role of NO produced by constitutive nitric oxide synthase (cNOS) in microglia is poorly understood. In this report, NO was found to regulate phagocytosis in murine BV-2 microglial cells as quantified by flow cytometry. Addition of NO-generating compounds caused impaired phagocytosis as compared to untreated microglia. The addition of nitric oxide synthase (NOS) inhibitors to microglial cells resulted in potentiation of phagocytosis, suggesting that constitutive NO was participating in the regulation of phagocytosis. The inverse correlation between NO production and phagocytosis was also observed when Alzheimer's beta-amyloid peptide was added. With beta-amyloid treatment, constitutive NO production decreased while phagocytosis increased. Cell extracts prepared from untreated microglia were found to contain both neuronal and endothelial NOS isoforms, but not the inducible form. The correlation of spontaneous NO production with attenuated phagocytosis suggests that constitutive NOS enzymes participate in microglial regulation.}, Author = {Kopec, K. K. and Carroll, R. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {1089-8603}, Journal = {Nitric Oxide}, Keywords = {Phagocytosis;Flow Cytometry;Fluorescein;11 Glia;Microglia;Nitric Oxide;Microspheres;Mice;Animals;Nitric-Oxide Synthase;Fluorescence;Isoenzymes}, Medline = {20297117}, Month = {4}, Nlm_Id = {9709307}, Number = {2}, Organization = {Department of Neuroscience Therapeutics, Division of Warner-Lambert, Parke-Davis Pharmaceutical Research, 2800 Plymouth Road, Ann Arbor, Michigan, 48105, USA.}, Pages = {103-11}, Pii = {S1089860300902805}, Pubmed = {10835290}, Title = {Phagocytosis is regulated by nitric oxide in murine microglia}, Uuid = {6CF5E2D0-15C8-4FA7-8DC2-A596CE053D43}, Volume = {4}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/niox.2000.0280}} @article{Kopen:1999, Abstract = {Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.}, Author = {Kopen, G. C. and Prockop, D. J. and Phinney, D. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Models, Biological;Cell Differentiation;Adipocytes;Chondrocytes;08 Aberrant cell cycle;Immunohistochemistry;Bone Marrow Cells;Astrocytes;Cerebellum;Bone Marrow Transplantation;Animals, Newborn;Prosencephalon;Animals;Cells, Cultured;Mice;Stromal Cells}, Medline = {99415924}, Month = {9}, Nlm_Id = {7505876}, Number = {19}, Organization = {Center for Gene Therapy, MCP Hahnemann University, 245 North 15th Street, Philadelphia, PA 19102-1192, USA.}, Pages = {10711-6}, Pubmed = {10485891}, Title = {Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains}, Uuid = {37E7113E-D3B2-11D9-A0E9-000D9346EC2A}, Volume = {96}, Year = {1999}} @article{Koppel:1983, Abstract = {The main tract of interhemispheric connections, the corpus callosum, is now suspected to contain more axons at birth than in adulthood. This notion is based on results obtained with retrograde pathway tracing techniques, but this indirect approach has several shortcomings. Since the elimination of projections during development now seems to be a general phenomenon, probably a crucial one in the establishment of connections, we have examined the development of the corpus callosum using quantitative electron microscopy. An average of 70\%of the callosal axons present at birth are eliminated by adulthood in the cat. We have also calculated a new figure of 23 million axons in the adult cat corpus callosum, which is over 4 times greater than the currently accepted figure.}, Author = {Koppel, H. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Corpus Callosum;Cats;Microscopy, Electron;Not relevant;11 Glia;Synaptic Transmission;Animals;Support, Non-U.S. Gov't;Neurons;Axons}, Medline = {84068804}, Month = {10}, Nlm_Id = {7600130}, Number = {1-2}, Pages = {33-40}, Pubmed = {6316219}, Title = {Is there a genuine exuberancy of callosal projections in development? A quantitative electron microscopic study in the cat}, Uuid = {7FDFAAAC-39AF-4AB3-8DB1-792E0BFCFBBD}, Volume = {41}, Year = {1983}} @article{Kornack:1998, Abstract = {The evolutionary expansion of neocortical size in mammals is particularly prominent in anthropoid primates (i.e., monkeys, apes, and humans) and reflects an increased number of cortical cells, yet the developmental basis for this increase remains undefined. Cortical cell production depends on the length of the cell-division cycle of progenitor cells during neurogenesis, which previously has been measured only in smaller-brained rodents. To investigate whether cortical expansion in primates reflects modification of cell-cycle kinetics, we determined cell-cycle length during neurogenesis in the proliferative cerebral ventricular zone of fetal rhesus monkeys, by using cumulative S-phase labeling with bromodeoxyuridine. Cell-cycle durations in monkeys were as much as 5 times longer than those reported in rodents. Nonetheless, substantially more total rounds of cell division elapsed during the prolonged neurogenetic period of the monkey cortex, providing a basis for increased cell production. Moreover, unlike the progressive slowing that occurs during cortical development in rodents, cell division accelerated during neurogenesis of the enlarged cortical layers in monkeys. These findings suggest that evolutionary modification of the duration and number of progenitor cell divisions contributed to both the expansion and laminar elaboration of the primate neocortex. 0027-8424 Journal Article}, Author = {Kornack, D. R. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {*Cell Cycle;Bromodeoxyuridine/pharmacokinetics;S Phase;Neocortex/*cytology/embryology/metabolism;Female;Macaca mulatta;Cell Division;Pregnancy;N;DNA Replication;Animals;Mice;Male;Support, U.S. Gov't, P.H.S.;19 Neocortical evolution}, Number = {3}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA. kornack\@biomed.med.yale.edu}, Pages = {1242-6}, Pubmed = {9448316}, Title = {Changes in cell-cycle kinetics during the development and evolution of primate neocortex}, Uuid = {70CCAD88-B220-4DDB-8037-4D85D994562D}, Volume = {95}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9448316}} @article{Kornack:1999, Abstract = {We present evidence for continuous generation of neurons, oligodendrocytes, and astrocytes in the hippocampal dentate gyrus of adult macaque monkeys, using immunohistochemical double labeling for bromodeoxyuridine and cell-type-specific markers. We estimate that the relative rate of neurogenesis is approximately 10 times less than that reported in the adult rodent dentate gyrus. Nevertheless, the generation of these three cell types in a discreet brain region suggests that a multipotent neural stem cell may be retained in the adult primate hippocampus. This demonstration of adult neurogenesis in nonhuman Old World primates-with their phylogenetic proximity to humans, long life spans, and elaborate cognitive abilities-establishes the macaque as an unexcelled animal model to experimentally investigate issues of neurogenesis in humans and offers new insights into its significance in the adult brain.}, Author = {Kornack, D. R. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;Oligodendroglia/metabolism;Neurons/*metabolism;Dentate Gyrus/*growth &development;Immunohistochemistry;Phylogeny;Cercopithecidae/physiology;Macaca/*physiology;Animal;Astrocytes/metabolism;Hippocampus/*growth &development;Evolution;Support, U.S. Gov't, P.H.S.;Bromodeoxyuridine;A-9a}, Number = {10}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510-8001, USA.}, Pages = {5768-73.}, Title = {Continuation of neurogenesis in the hippocampus of the adult macaque monkey}, Uuid = {5064D6D4-CCDD-11D9-8C77-000D9346EC2A}, Volume = {96}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10318959%20http://www.pnas.org/cgi/content/full/96/10/5768}} @article{Kornack:2001, Abstract = {In adult rodents, neural progenitor cells in the subependymal (SZ) zone of the lateral cerebral ventricle generate neuroblasts that migrate in chains via the rostral migratory stream (RMS) into the olfactory bulb (OB), where they differentiate into interneurons. However, the existence of this neurogenic migratory system in other mammals has remained unknown. Here, we report the presence of a homologue of the rodent SZ/RMS in the adult macaque monkey, a nonhuman Old World primate with a relatively smaller OB. Our results-obtained by using combined immunohistochemical detection of a marker for DNA replication (5- bromodeoxyuridine) and several cell type-specific markers-indicate that dividing cells in the adult monkey SZ generate neuroblasts that undergo restricted chain migration over an extended distance of more than 2 cm to the OB and differentiate into granule interneurons. These findings in a nonhuman primate extend and support the use of the SZ/RMS as a model system for studying neural regenerative mechanisms in the human brain.}, Author = {Kornack, D. R. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {*Cell Movement;02 Adult neurogenesis migration;B both;Olfactory Pathways/*cytology;Immunohistochemistry;Macaca mulatta;Phenotype;Macaca fascicularis;Animal;*Cell Differentiation;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Brain/*cytology;Primates}, Number = {8}, Organization = {Center for Aging and Developmental Biology, Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY 14642, USA. david.kornack\@urmc.rochester.edu}, Pages = {4752-7.}, Title = {The generation, migration, and differentiation of olfactory neurons in the adult primate brain}, Uuid = {A4E75311-F4A5-474D-B396-A1E08C3A507D}, Volume = {98}, Year = {2001}, url = {papers/Kornack_ProcNatlAcadSciUSA2001}} @article{Kornack:2001a, Abstract = {A recent assertion that new neurons are continually added to the neocortex of adult macaque monkeys has profound implications for understanding the cellular mechanisms of higher cognitive functions. Here we searched for neurogenesis in adult macaques by using immunofluorescent triple labeling for the DNA-replication indicator, bromodeoxyuridine (BrdU), and neuronal and glial cell markers. Although numerous BrdU-labeled cells were distributed throughout the cerebral wall, including the neocortex, these were identified as nonneuronal cells; evidence for newly generated neurons was limited to the hippocampus and olfactory bulb. Thus, our results do not substantiate the claim of neurogenesis in normal adult primate neocortex.}, Author = {Kornack, D. R. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {Science}, Keywords = {Tubulin/analysis;Fluorescent Antibody Technique;Neurons/*cytology;Microscopy, Confocal;Immunoenzyme Techniques;Neocortex/*cytology;Endothelium, Vascular/cytology;Female;Animal;Glial Fibrillary Acidic Protein/analysis;Bromodeoxyuridine/analysis/metabolism;Cell Movement;Macaca fascicularis;Microscopy, Fluorescence;Male;Nuclear Proteins/analysis;Brain/cytology;Macaca mulatta;Support, U.S. Gov't, P.H.S.;Cell Death;A pdf;Astrocytes/cytology;*Cell Division}, Number = {5549}, Organization = {Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.}, Pages = {2127-30.}, Title = {Cell proliferation without neurogenesis in adult primate neocortex}, Uuid = {55FF2A1E-CDF0-11D9-B244-000D9346EC2A}, Volume = {294}, Year = {2001}, url = {papers/Kornack_Science2001.pdf}} @article{Kornblum:2001, Abstract = {The study of neural stem cell biology is hindered by the absence of well-defined markers for neural stem cells and neuronal progenitors. Without the ability to identify the relevant cell types, the analysis of how the diverse cell populations of the central nervous system are generated becomes virtually impossible.}, Author = {Kornblum, H. I. and Geschwind, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {10 Development;F pdf}, Number = {11}, Organization = {Harley I. Kornblum is at the Department of Molecular and Medical Pharmacology, the Department of Pediatrics and the Crump Institute for Molecular Imaging, UCLA School of Medicine, Los Angeles, California 90095, USA.}, Pages = {843-6.}, Title = {Molecular markers in CNS stem cell research: hitting a moving target}, Uuid = {0F8D7E6A-9AF9-4DFC-999C-08001209CC04}, Volume = {2}, Year = {2001}, url = {papers/Kornblum_NatRevNeurosci2001.pdf}} @article{Korr:1999, Abstract = {In a recent paper (Shankle et al., 1998a), post-natal neurogenesis in the human cerebral cortex was discussed. Based on re-calculations of morphometric data from the literature, the authors concluded an average 1.1\%monthly increase in post-natal cortical neuron number between post-natal months 15-72. The present paper makes clear by discussing four main assumptions done by Shankle et al., i.e. shrinkage of the tissue, morphometric features of the neurons under study, conversion of cell densities per area to number per unit volume and estimation of coefficients of variation, that their final conclusion about an increase in neuron number is unsound. Furthermore, five points are discussed here that Shankle et al. had mentioned in order to demonstrate that the pulse thymidine labeling method is less reliable than some have assumed. The present paper refute these assumptions point by point. Thus, the Shankle et al. paper does not provide scientifically valid evidence of a post-natal neurogenesis in the developing human cerebral cortex.}, Author = {Korr, H. and Schmitz, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0022-5193}, Journal = {J Theor Biol}, Keywords = {Adolescent;Infant;Autoradiography;Models, Neurological;Cell Count;Child, Preschool;Child;Humans;Cerebral Cortex;Neurons}, Medline = {99459024}, Month = {10}, Nlm_Id = {0376342}, Number = {3}, Organization = {Department of Anatomy and Cell Biology, RWTH University of Aachen, Pauwelsstrasse 30/Wendlingweg 2, Aachen, D-52057, Germany. korr\@post.klinikum.rwth-aachen.de}, Pages = {291-7}, Pii = {S002251939990992X}, Pubmed = {10527718}, Title = {Facts and fictions regarding post-natal neurogenesis in the developing human cerebral cortex}, Uuid = {BAA1552F-C26D-11DA-969D-000D9346EC2A}, Volume = {200}, Year = {1999}, url = {papers/Korr_JTheorBiol1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/jtbi.1999.0992}} @article{Kosaka:2007, Abstract = {We analyzed the cellular composition of the juxtaglomerular region in the main olfactory bulb of C57B/6J strain mice, focusing on 1) the compartmental organization of the glomerulus and the presence of type 1 and 2 periglomerular cells, 2) the colocalization relationships among the 4 major chemically identified groups of periglomerular cells, glutamic acid decarboxylase (GAD)/gamma-aminobutyric acid (GABA), tyrosine hydroxylase, calretinin and calbindin D28k positive periglomerular cells, and 3) the chemical properties of the nitric oxide synthase (NOS)-positive juxtaglomerular cells. We confirmed the compartmental organization of the glomerulus and the presence of both type 1 and 2 periglomerular cells in the mice. Similar to rat periglomerular cells, the tyrosine hydroxylase-positive cells were type 1 and GAD/GABA-positive. On the other hand, both the calbindin D28k-positive and calretinin-positive cells were type 2 periglomerular cells, but in contrast to those in rats, which are GAD/GABA-negative, all of the calbindin D28k-positive periglomerular cells and 65\%of the calretinin-positive periglomerular cells were GAD/GABA-positive. The GAD/GABA-positive cells thus included both type 1 and type 2 periglomerular cells. Juxtaglomerular NOS-positive cells have been proposed as a subgroup of type 1 periglomerular cells that are separate from the calretinin-positive and calbindin D28k-positive cells in rats. However, in the mice, about 70\%of the NOS-positive cells were calretinin-positive, and 50\%of the calretinin-positive cells were NOS-positive. We herein reveal the significant species differences in the chemical properties of periglomerular cells and suggest that the cellular organization of the mouse main olfactory bulb cannot be extrapolated from that of rats.}, Author = {Kosaka, Katsuko and Kosaka, Toshio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {0045503}, Organization = {School of Health Sciences, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan. kosaka\@shs.kyushu-u.ac.jp}, Pages = {42-55}, Pii = {S0006-8993(07)01347-9}, Pubmed = {17662264}, Title = {Chemical properties of type 1 and type 2 periglomerular cells in the mouse olfactory bulb are different from those in the rat olfactory bulb}, Uuid = {7ABA0134-33F5-479C-A1DA-95D32E8BBB6F}, Volume = {1167}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainres.2007.04.087}} @article{Kosaka:1996, Abstract = {Synaptic contacts on the granule cell somata as well as on their axon initial segments in the dentate gyrus of one juvenile 5-week-old rat and one adult 12-week-old rat were analyzed in an electron microscopic serial-sectioning study. In the dentate gyrus of the juvenile rat, somata of 17 granule cells were nearly completely reconstructed from a series of 183 serial sections, and the axon initial segments of 15 of these granule cells were traced in various lengths. On the other hand, in the dentate gyrus of the adult rat, somata of 31 granule cells were almost completely reconstructed from a series of 238 serial sections, and the axon initial segments of 23 of these granule cells were traced in various lengths. Both symmetrical and asymmetrical synapses were observed on the somata, whereas almost all synapses on the axon initial segments were of symmetrical type and asymmetrical synapses on the axon initial segments were rather exceptional. Although we confirmed two conclusions from previous random-section studies to some extent, that is, the superficial-to-deep gradient of synaptic densities on granule cell somata and the presence of a substantial number of asymmetrical synapses on granule cell somata (about 23\%of total somatic synapses), the present serial-sectioning study clearly revealed that granule cells vary greatly with regard to the number of synapses on their somata (15-186 in a 5-week-old rat and 9-144 in a 12-week-old rat) and axon initial segments. The granule cells also differed in the proportion of somatic asymmetrical synapses to total synapses they received (0-44\%in a 5-week-old rat and 0-60\%in a 12-week-old rat). The results of the present study indicated that, when a relatively small number of granule cells are analyzed, one should take the heterogeneity of synaptic contacts on granule cells in number and type into consideration.}, Author = {Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Synapses;10 Development;Research Support, Non-U.S. Gov't;Rats;10 Hippocampus;Microscopy, Electron;Dentate Gyrus;Rats, Wistar;Animals;Male;Neurons}, Medline = {97109112}, Month = {11}, Nlm_Id = {0043312}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Kyushu University, Fukuoka, Japan.}, Pages = {237-43}, Pubmed = {8951392}, Title = {Synapses in the granule cell layer of the rat dentate gyrus: serial-sectioning study}, Uuid = {727304DF-1BB8-435E-9ECB-917E46C78439}, Volume = {112}, Year = {1996}} @article{Kosaka:1986, Abstract = {Structural features of astrocytes in the rat dentate gyrus were studied by means of light and high-voltage electron microscopy of Golgi-impregnated materials, conventional electron microscopy, combined Golgi-electron microscopy, and immunohistochemistry for glial fibrillar acidic protein. Astrocytes in the dentate gyrus were of the protoplasmic type and were classified into six subtypes based on the location of their somata; i.e., astrocytes in the polymorph layer, in the subgranular zone, in the granular cell layer, at the border of the granular cell layer and the molecular layer, in the molecular layer, and subjacent to the pia surface. Stereoscopic observations of 5-micron-thick sections of Golgi-impregnated materials revealed three-dimensional structural details of astroglial processes not apparent in either the light microscope or in conventional thin-section electron microscopy. Most of them were basically thin sheets, varying in shape and size in accordance with their sites. In the granule cell layer, thin veillike sheets or lamellae, originating from three kinds of astrocytes (subtypes 2, 3, and 4), intervened between granule cell somata, whereas in the plexiform and molecular layers small leafletlike appendages originating from astrocytes (subtypes 1, 2, 4, and 5) intermingled with one another, making spongelike conglomerates. Thus astrocytes in the subgranular zone and those at the border of the granule cell layer and the molecular layer showed prominent regional differentiation of their processes among layers. In addition to these sheetlike processes, thin threadlike processes were also common.}, Author = {Kosaka, T. and Hama, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:25 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {10 Development;Glial Fibrillary Acidic Protein;Research Support, Non-U.S. Gov't;Rats;10 Hippocampus;Microscopy, Electron;Astrocytes;Hippocampus;Immunoenzyme Techniques;Male;Animals;Rats, Inbred Strains}, Medline = {86278976}, Month = {7}, Nlm_Id = {0406041}, Number = {2}, Pages = {242-60}, Pubmed = {3525618}, Title = {Three-dimensional structure of astrocytes in the rat dentate gyrus}, Uuid = {C99C9F35-18A0-40A1-AB97-192892A7D220}, Volume = {249}, Year = {1986}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902490209}} @article{Kosaka:2001, Abstract = {Intraglomerular dendritic tufts of Golgi-impregnated and biotinylated dextran amine (BDA)-labeled mitral cells in the rat main olfactory bulb were analyzed in detail. In particular, the relationships of BDA- labeled tufts with olfactory nerve (ON) terminals and processes of calbindin D-28K-immunoreactive (CB-IR) cells were investigated with confocal laser-scanning light microscopic (CLSM) and electron microscopic (EM) analyses. CB-IR cells were type 2 periglomerular cells that restricted their processes in the ON-free (non-ON) zone of the glomerulus and received few synapses from ON terminals. The mitral tufts varied in complexity, but individual branches were rather simple, smooth processes that bore some branchlets and spines and extended more or less in a straight line or a gentle curve rather than winding tortuously within glomeruli as though they did not consider the compartmental organization, which consisted of ON and non-ON zones that interdigitated in a complex manner with one another. Conventional EM analysis revealed that both thin and thick, presumed proximal branches of mitral/tufted cell dendritic tufts received asymmetrical synapses from ON terminals. Correlated CLSM-EM analysis confirmed direct contacts between the BDA- and CB-labeled processes detected in the CLSM examinations, and synapses were recognized at some of those sites. Furthermore, ON terminals and CB-IR processes were distributed on both proximal and distal dendritic branches in a more or less mosaic pattern. These findings revealed that, on the mitral dendritic tufts, ON terminals and processes of type 2 periglomerular neurons were not clearly segregated proximodistally but, rather, were arranged in a mosaic pattern, which may be important in fine tuning the output from individual glomeruli.}, Author = {Kosaka, K. and Aika, Y. and Toida, K. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {J Comp Neurol}, Keywords = {Calcium-Binding Protein, Vitamin D-Dependent/*metabolism;Olfactory Nerve/*physiology;Fluorescent Dyes;Axons/physiology;13 Olfactory bulb anatomy;Golgi Apparatus/ultrastructure;Olfactory Bulb/*cytology;Rats;Dextrans;Microscopy, Confocal;Neurons/classification/*physiology/*ultrastructure;Animal;Rats, Wistar;Male;Support, Non-U.S. Gov't;Biotin/*analogs &derivatives;Dendrites/*physiology/*ultrastructure;I pdf;Microscopy, Electron;Nerve Endings/physiology}, Number = {3}, Organization = {Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. kosaka\@shs.kyushu- u.ac.jp}, Pages = {219-35.}, Title = {Structure of intraglomerular dendritic tufts of mitral cells and their contacts with olfactory nerve terminals and calbindin-immunoreactive type 2 periglomerular neurons}, Uuid = {D0208EFE-DE5B-4800-A729-E10DFAF23396}, Volume = {440}, Year = {2001}, url = {papers/Kosaka_JCompNeurol2001}} @article{Kosaka:1995, Abstract = {Chemically-defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb were revealed immunocytochemically using antibodies against gamma-amino butyric acid (GABA), tyrosine hydroxylase (TH), methionin-enkephalin-Arg6-Gly7-Leu8 (ENK), calretinin (CR), calbindin-D28K (calbindin) and thyrotropin- releasing hormone (TRH). GABA-like immunoreactive (GABA-LIR) neurons and CR immunoreactive (CR-IR) neurons were most numerous; they were about 1.5-3 times more numerous than calbindin immunoreactive (calbindin-IR), TH immunoreactive (TH-IR), ENK-like immunoreactive (ENK- LIR) and THR-like immunoreactive (TRH-LIR) neurons. We identified at least three distinct chemically-defined neuron groups, GABA-LIR neurons, CR containing neurons and calbindin containing neurons, since these three neuron groups were almost separate from one another. On the other hand, TH-IR and ENK-LIR neurons were nearly included in and thus considered to be subpopulations of GABA-LIR and CR-IR neurons, respectively, for about 80\%of these two neuron groups contained GABA-L and CR immunoreactivities, respectively. TRH-LIR neurons appeared to be divided into two subpopulations, one containing the GABA-L immunoreactivity and the other containing the CR immunoreactivity. Thus in the glomerular layer of the rat olfactory bulb, GABA-LIR, CR-IR and calbindin-IR cells could be considered to be three distinct chemically- defined neuron groups, whereas TH-IR, TRH-LIR and ENK-LIR neurons were regarded as their subpopulations. Furthermore, some neurons groups, whereas TH-IR, TRH-LIR and ENK-LIR neurons were regarded as their subpopulations. Furthermore, some neurons are supposed to contain three substances (e.g. GABA + TH + TRH, GABA + TRH + EnK, CR + TRH + ENK, GABA + TRH + CR) or a few might even contain four substances (e.g. GABA + TRH + CR + ENK). Preliminary quantitative analysis using the optical disector method showed percentages of these three main neuron groups to total cells in the glomerular layer; that is, neuron groups containing GABA, CR and calbindin were about 20\%, 20\%and 10\%, respectively.}, Author = {Kosaka, K. and Aika, Y. and Toida, K. and Heizmann, C. W. and Hunziker, W. and Jacobowitz, D. M. and Nagatsu, I. and Streit, P. and Visser, T. J. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Neurosci Res}, Keywords = {Microscopy, Confocal;Tyrosine 3-Monooxygenase/immunology;Antibodies/*immunology;GABA/immunology;Immunohistochemistry;Rats;Protirelin/immunology;Rats, Wistar;Cell Count;Animal;Neurons/*classification/*immunology;Olfactory Bulb/*physiology;Support, Non-U.S. Gov't;Male;13 Olfactory bulb anatomy;I both}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.}, Pages = {73-88.}, Title = {Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb}, Uuid = {AFA26055-926D-4D57-8FD9-6A1CBAB62C24}, Volume = {23}, Year = {1995}, url = {papers/Kosaka_NeurosciRes1995.pdf}} @article{Kosaka:1998, Abstract = {Recent progress in the studies of the olfactory system, especially in the molecular biological studies, makes it one of the useful sensory model systems for understanding neural mechanisms for the information processing. In the olfactory bulb, the primary center of the olfactory system, glomeruli are regarded as important functional units in the transmission of odorant signals and in processing the olfactory information, but have been believed to be composed by only a small number of neuronal types and thus to be simple in their neuronal and synaptic organization. However, accumulating morphological data reveal that each type of neurons might further consist of several different subpopulations, indicating that the organization of glomeruli might not be so simple as it was believed. Here we describe an aspect of the structural organization of glomeruli, focusing on the heterogeneities of periglomerular neurons in mammalian main olfactory bulb.}, Author = {Kosaka, K. and Toida, K. and Aika, Y. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Neurosci Res}, Keywords = {Neurons/*cytology/*physiology;I;Neuropeptides/analysis;Mammals;Animal;Olfactory Bulb/*anatomy &histology/cytology/*physiology;Calcium-Binding Proteins/analysis;Support, Non-U.S. Gov't;13 Olfactory bulb anatomy}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan. katsuko\@a3rd.med.kyushu-u.ac.jp}, Pages = {101-10.}, Title = {How simple is the organization of the olfactory glomerulus?: the heterogeneity of so-called periglomerular cells}, Uuid = {ED88B049-5A76-4FE3-9695-C993E0D08179}, Volume = {30}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9579643}} @article{Kosaka:2004, Abstract = {In the mouse main olfactory bulb (MOB) gap junction-forming processes in glomeruli were analyzed by means of the serial electron microscopical reconstruction. Gap junctions were encountered between diverse types of dendritic processes and thus confirming our previous study on gap junctions in the rat MOB. Importantly, among more than 30 gap junctions examined in serial sections, we encountered 3 gap junctions made between mitral/tufted cell dendrites in the glomerulus. Then we must consider both direct coupling between mitral/tufted cells via gap junctions and indirect coupling between mitral/tufted cells via intervening interneuronal processes as suggested previously. 0168-0102 Journal Article}, Author = {Kosaka, T. and Kosaka, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Neurosci Res}, Keywords = {I pdf;13 Olfactory bulb anatomy}, Number = {4}, Organization = {Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.}, Pages = {373-8}, Title = {Neuronal gap junctions between intraglomerular mitral/tufted cell dendrites in the mouse main olfactory bulb}, Uuid = {AAA97934-5365-4DED-9384-A371DA8DCEB5}, Volume = {49}, Year = {2004}, url = {papers/Kosaka_NeurosciRes2004.pdf}} @article{Kosaka:2006, Abstract = {The distribution and structural features of nitric acid synthase (NOS) containing intrinsic neurons were studied in the mouse main olfactory bulb (MOB). NOS positive neurons were heterogeneous, including some subpopulations of periglomerular cells, granule cells, interneurons in the external plexiform layer, superficial and deep short-axon cells and stellate cells. NOS positive periglomerular cells were frequently calretinin immunoreactive and, although rarely, calbindin positive. Importantly, some middle and external tufted cells were also confirmed to be NOS positive, some of which were also cholecystokinin (CCK) positive. Retrograde tracer experiments showed that some NOS positive tufted cells, which were also CCK positive, constitute the intrabulbar association system and the projection system to the olfactory tubercle. In addition, another particular subpopulation of NOS positive neurons with no or little CCK immunoreactivity appeared to project to areas covering the dorsal endopiriform nucleus, claustrum and insular cortex. Furthermore, diverse types of neurons other than mitral/tufted cells were also suggested to be projection neurons of the MOB. The present study revealed the diversity of NOS positive neurons in the mouse MOB and further revealed that they were different from those reported previously in the rat MOB in structural and chemical properties.}, Author = {Kosaka, and Kosaka,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {24 Pubmed search results 2008;13 Olfactory bulb anatomy}, Month = {11}, Nlm_Id = {8500749}, Organization = {Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Higashiku, Fukuoka 812-8582, Japan.}, Pii = {S0168-0102(06)00277-X}, Pubmed = {17134781}, Title = {Heterogeneity of nitric oxide synthase-containing neurons in the mouse main olfactory bulb}, Uuid = {E55F435C-7671-407D-8FBB-3D4902AC8516}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neures.2006.10.005}} @article{Kosaka:1997, Abstract = {In the glomerular layer of the rat main olfactory bulb, we previously reported three chemically defined interneuron groups: GABA-like immunoreactive, calretinin-immunoreactive and Calbindin-D28k- immunoreactive groups [Kosaka K. et al. (1995) Neurosci. Res. 23, 73- 88]. In the present study, we analysed the structural features of these three neuron groups using confocal laser scanning light microscopy, focusing on their dendritic arborization pattern, especially on their close apposition to olfactory receptor terminals labeled by olfactory marker protein. Each glomerulus consisted of two zones, the olfactory nerve zone and the non-olfactory nerve zone. The former was mainly occupied by olfactory nerve preterminals and terminals as well as their targets, postsynaptic fine dendritic portions of intrinsic neurons. The latter non-olfactory nerve zone was occupied mainly by olfactory marker protein-negative profiles. Processes of GABAergic neurons and those of one of their subpopulations, tyrosine hydroxylase-immunoreactive neurons, were numerous both in the olfactory nerve and non-olfactory nerve zones, resulting in their frequent close apposition to olfactory marker protein-immunoreactive elements. Combined confocal laser scanning light microscopic electron microscopic examination revealed synaptic contacts from olfactory nerve terminals on tyrosine hydroxylase-immunoreactive processes at these sites of close apposition. In contrast, calretinin-immunoreactive and Calbindin-D28k- immunoreactive processes, particularly Calbindin-D28k-immunoreactive ones, were distributed almost exclusively in the non-olfactory nerve zone, as if they avoided the olfactory nerve zone, showing a net or honeycomb pattern. Thus, calretinin-immunoreactive and Calbindin-D28k- immunoreactive processes were not or very rarely closely apposed to olfactory nerve terminals. These findings suggested that there might be some differences among chemically defined interneuronal groups in their synaptic contacts from olfactory nerves. Further quantitative image analysis clearly exhibited the prominent differences among these neuron groups in their intraglomerular dendritic arborization in relation with the olfactory nerve zone, i.e. the percentages of the area in the olfactory nerve zone occupied by GABAergic and tyrosine hydroxylase- immunoreactive processes were about 10\%, respectively, whereas those of calretinin-immunoreactive and Calbindin-D28k-immunoreactive processes were only about 1\%and 0.3\%, respectively. These findings suggested that so-called periglomerular cells in glomeruli might be heterogeneous not only in their chemical nature, but also in their dendritic arborization pattern and synaptic contacts from olfactory nerve terminals.}, Author = {Kosaka, K. and Toida, K. and Margolis, F. L. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:55 -0400}, Journal = {Neuroscience}, Keywords = {Microscopy, Confocal;I;Fluorescent Antibody Technique, Indirect;Olfactory Bulb/*cytology/metabolism/ultrastructure;Rats;Immunohistochemistry;Neurons/metabolism/*physiology/ultrastructure;Microscopy, Electron, Scanning;Rats, Wistar;Presynaptic Terminals/metabolism/*physiology/ultrastructure;Animal;Dendrites/metabolism/*physiology/ultrastructure;Calcium-Binding Protein, Vitamin D-Dependent/metabolism;Support, Non-U.S. Gov't;Male;Olfactory Nerve/cytology/*physiology/ultrastructure;13 Olfactory bulb anatomy}, Number = {3}, Organization = {Department of Anatomy and Neurobiology, Faculty of Medicine, Kyushu University, Higashi-ku, Fukuoka, Japan.}, Pages = {775-86.}, Title = {Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb--II. Prominent differences in the intraglomerular dendritic arborization and their relationship to olfactory nerve terminals}, Uuid = {AF344FC4-0EEB-480D-9476-716D07A63043}, Volume = {76}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9135050}} @article{Kothare:1998, Abstract = {The association between gray matter heterotopias and seizures is well established; whether seizures originate from these lesions is not known. We evaluated three patients with intractable complex partial seizures and periventricular nodular heterotopias (PNHs) with video-EEG monitoring with multiple depth electrodes, including placement in the PNH, to determine whether seizures originate from the PNH. In two of the three patients, all seizures arose from the PNH as low-voltage beta activity. In the third patient, 80\%arose from the hippocampi and 20\%from the heterotopia. PNHs may serve as an epileptogenic focus in patients with intractable epilepsy.}, Author = {Kothare, S. V. and VanLandingham, K. and Armon, C. and Luther, J. S. and Friedman, A. and Radtke, R. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {Brain Diseases;10 Development;Electroencephalography;Adult;Epilepsy, Complex Partial;Magnetic Resonance Imaging;Female;Hippocampus;Electrodes;Choristoma;10 genetics malformation;Cerebral Ventricles;Humans;Male;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {0401060}, Number = {6}, Organization = {Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.}, Pages = {1723-7}, Pubmed = {9855532}, Title = {Seizure onset from periventricular nodular heterotopias: depth-electrode study}, Uuid = {BA907C55-EFB6-4AE5-BBD4-5DBFB72F6F8F}, Volume = {51}, Year = {1998}} @article{Koulakov:2004, Abstract = {BACKGROUND: We examine results of gain-of-function experiments on retinocollicular maps in knock-in mice [Brown et al. (2000) Cell 102:77]. In wild-type mice the temporal-nasal axis of retina is mapped to the rostral-caudal axis of superior colliculus. The established map is single-valued, which implies that each point in retina maps to a unique termination zone in superior colliculus. In homozygous Isl2/EphA3 knock-in mice the map is double-valued, which means that each point on retina maps to two termination zones in superior colliculus. This is because about 50 percent of cells in retina express Isl2, and two types of projections, wild-type and Isl2/EphA3 positive, form two branches of the map. In heterozygous Isl2/EphA3 knock-ins the map is intermediate between the homozygous and wild-type: it is single-valued in temporal and double-valued in the nasal parts of retina. In this study we address possible reasons for such a bifurcation of the map. RESULTS: We study the map formation using stochastic model based on Markov chains. In our model the map undergoes a series of reconstructions with probabilities dependent upon a set of chemical cues. Our model suggests that the map in heterozygotes is single-valued in temporal region of retina for two reasons. First, the inhomogeneous gradient of endogenous receptor in retina makes the impact of exogenous receptor less significant in temporal retina. Second, the gradient of ephrin in the corresponding region of superior colliculus is smaller, which reduces the chemical signal-to-noise ratio. We predict that if gradient of ephrin is reduced by a genetic manipulation, the single-valued region of the map should extend to a larger portion of temporal retina, i.e. the point of transition between single-and double-valued maps should move to a more nasal position in Isl2-EphA3 heterozygotes. CONCLUSIONS: We present a theoretical model for retinocollicular map development, which can account for intriguing behaviors observed in gain-of-function experiments by Brown et al., including bifurcation in heterozygous Isl2/EphA3 knock-ins. The model is based on known chemical labels, axonal repulsion/competition, and stochasticity. Possible mapping in Isl2/EphB knock-ins is also discussed.}, Author = {Koulakov, Alexei A. and Tsigankov, Dmitry N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1471-2202}, Journal = {BMC Neurosci}, Keywords = {Stochastic Processes;10 Development;Heterozygote;Animals;Transcription Factors;Retina;Ephrins;Superior Colliculi;Markov Chains;Homeodomain Proteins;Axons;Receptor, EphA3;Mice, Transgenic;Ephrin-B2;10 circuit formation;Homozygote;21 Neurophysiology;Mice;24 Pubmed search results 2008;Ephrin-B3;Models, Neurological;Ligands;Retinal Ganglion Cells}, Month = {8}, Nlm_Id = {100966986}, Organization = {Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, NY, 11724, USA. akula\@cshl.edu}, Pages = {30}, Pii = {1471-2202-5-30}, Pubmed = {15339341}, Title = {A stochastic model for retinocollicular map development}, Uuid = {D5B1F724-1B67-4AE5-90DD-7E5827B4F004}, Volume = {5}, Year = {2004}, url = {papers/Koulakov_BMCNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1471-2202-5-30}} @article{Kovac:2004, Abstract = {Entorhinal cortex lesion (ECL) is a well described model of anterograde axonal degeneration, subsequent sprouting and reactive synaptogenesis in the hippocampus. Here, we show that such lesions induce transsynaptic degeneration of the target cells of the lesions pathway in the dentate gyrus. Peaking between 24 and 36 hours post-lesion, dying neurons were labeled with DeOlmos silver-staining and antisera against activated caspase 3 (CCP32), a downstream inductor of programmed cell death. Within caspase 3-positive neurons, fragmented nuclei were co-localized using Hoechst 33342 staining. Chromatin condensation and nuclear fragmentation were also evident in semithin sections and at the ultrastructural level, where virtually all caspase 3-positive neurons showed these hallmarks of apoptosis. There is a well-described upregulation of the apoptosis-inducing CD95/L system within the CNS after trauma, yet a comparison of caspase 3-staining patterns between CD95 (Ipr)- and CD95L (gld)-deficient with non-deficient mice (C57/bl6) provided no evidence for CD95L-mediated neuronal cell death in this setting. However, inhibition of NMDA receptors with MK-801 completely suppressed caspase 3 activation, pointing to glutamate neurotoxicity as the upstream inducer of the observed cell death. Thus, these data show that axonal injury in the CNS does not only damage the axotomized neurons themselves, but can also lethally affect their target cells, apparently by activating glutamate-mediated intracellular pathways of programmed cell death.}, Author = {Kovac, Adam D. and Kwidzinski, Erik and Heimrich, Bernd and Bittigau, Petra and Deller, Thomas and Nitsch, Robert and Bechmann, Ingo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {1015-6305}, Journal = {Brain Pathol}, Keywords = {Excitatory Amino Acid Antagonists;Animals;Synapses;Enzyme Activation;Glutamic Acid;Comparative Study;Dizocilpine Maleate;Apoptosis;Entorhinal Cortex;Caspases;Perforant Pathway;11 Glia;Male;Membrane Glycoproteins;Axotomy;Neurons;Mice;Microscopy, Electron;Immunohistochemistry;Antigens, CD95;Research Support, Non-U.S. Gov't}, Medline = {23561092}, Month = {7}, Nlm_Id = {9216781}, Number = {3}, Organization = {Institute of Anatomy, Deptment of Cell and Neurobiology, Charit{\'e}, University Medicine, Berlin, Germany.}, Pages = {249-57}, Pubmed = {15446579}, Title = {Entorhinal cortex lesion in the mouse induces transsynaptic death of perforant path target neurons}, Uuid = {36E3689F-887B-44A2-A900-8B7684B2937C}, Volume = {14}, Year = {2004}} @article{Kozlowski:2000, Abstract = {The effects of delivering GDNF via an adenoviral vector (AdGDNF) 1 week after lesioning dopaminergic neurons in the rat substantia nigra (SN) with 6-hydroxydopamine (6-OHDA) were examined. Rats were unilaterally lesioned by injection of 6-OHDA into the striatum, resulting in progressive degeneration of dopaminergic neurons in the SN. One week later, when substantial damage had already occurred, AdGDNF or a control vector harboring beta-galactosidase (AdLacZ) was injected into either the striatum or SN (3.2 x 10(7) PFU/microl in 2 microl). Rats were examined behaviorally with the amphetamine-induced rotation test and for forelimb use for weight-bearing movements. On day 30 postlesion, the extent of nigrostriatal tract degeneration was determined by injecting a retrograde tracer (FluoroGold) bilaterally into the lesioned striatum. Five days later, rats were sacrificed within 2 h of amphetamine injection to examine amphetamine-induced Fos expression in the striatum, a measure of dopaminergic-dependent function in target neurons. AdGDNF injection in the SN rescued dopaminergic neurons in the SN and increased the number of dopaminergic neurons that maintained a connection to the striatum, compared to rats injected with AdLacZ. Further support that these spared SN cells maintained functional connections to the striatum was evidenced by increased Fos expression in striatal target neurons and a decrease in amphetamine-induced rotation. In contrast to the effects observed in rats injected with AdGDNF in the SN, rats injected with AdGDNF in the striatum did not exhibit significant ameliorative effects. This study demonstrates that experimentally increasing levels of GDNF biosynthesis near the dopaminergic neuronal soma is effective in protecting the survival of these neurons and their function even when therapy is begun after 6-OHDA-induced degeneration has commenced. Thus, GDNF gene therapy may ameliorate the consequences of Parkinson's disease through rescuing compromised dopaminergic neurons.}, Author = {Kozlowski, D. A. and Connor, B. and Tillerson, J. L. and Schallert, T. and Bohn, M. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Fluorescent Dyes;Motor Activity;Dopamine;Nerve Degeneration;Animals;Rats;Neural Pathways;Recovery of Function;Parkinson Disease;Substantia Nigra;Nerve Growth Factors;Male;Rats, Inbred F344;Proto-Oncogene Proteins c-fos;Research Support, U.S. Gov't, P.H.S.;Neostriatum;Neurons;Gene Therapy;Tyrosine 3-Monooxygenase;24 Pubmed search results 2008;Nerve Tissue Proteins;Oxidopamine;Research Support, Non-U.S. Gov't}, Medline = {20487523}, Month = {11}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Pediatrics, Children's Memorial Institute for Education and Research, Chicago, Illinois 60614, USA.}, Pages = {1-15}, Pii = {S0014488600974636}, Pubmed = {11031079}, Title = {Delivery of a GDNF gene into the substantia nigra after a progressive 6-OHDA lesion maintains functional nigrostriatal connections}, Uuid = {7EF62F54-2685-459A-90D6-43071E74A319}, Volume = {166}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.2000.7463}} @article{Kozorovitskiy:2003, Author = {Kozorovitskiy, Yevgenia and Gould, Elizabeth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {Purkinje Cells;Cell Fusion;08 Aberrant cell cycle;Stem Cells;Bone Marrow Transplantation;22 Stem cells;comment;Animals;Brain;Mice;24 Pubmed search results 2008;news}, Month = {11}, Nlm_Id = {100890575}, Number = {11}, Pages = {952-4}, Pii = {ncb1103-952}, Pubmed = {14593417}, Title = {Stem cell fusion in the brain}, Uuid = {BB56ABD9-822D-4D91-81EF-C6B23561B182}, Volume = {5}, Year = {2003}, url = {papers/Kozorovitskiy_NatCellBiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb1103-952}} @article{Kohr:1991, Abstract = {Nerve cells that lack the cytoplasmic Ca2+ binding protein Calbindin-D28K (CaBP) appear to be selectively vulnerable to Ca(2+)-related injury consistent with a postulated intraneuronal Ca(2+)-buffering role of CaBP. We have confirmed the selective loss of CaBP from the dentate gyrus during kindling-induced epilepsy in acutely dissociated granule cells (GCs) from kindled rats. Immunohistochemically stained kindled neurons showed a significant loss of CaBP when compared to controls (p less than 0.001; ANOVA). The Ca(2+)-buffering role of CaBP was assessed in acutely dissociated control and kindled GCs by examining a physiological process highly sensitive to intracellular Ca(2+)-buffering: the Ca(2+)-dependent inactivation of high-voltage activated (HVA or L-type) Ca2+ currents in the absence (or presence) of exogenous Ca(2+)-chelators. Whole-cell patch clamp recordings in kindled GCs demonstrated a markedly enhanced Ca(2+)-dependent inactivation of Ca(2+)-currents. After brief conditioning Ca2+ currents, in the absence of an exogenous intraneuronal Ca(2+)-chelator, subsequent test Ca2+ currents were inactivated by 58.3\%in kindled GCs, a significant increase from the 37.4\%inactivation observed in control GCs (p less than 0.005; ANOVA). The differential Ca2+ current decay and Ca(2+)-dependent inactivation were prevented in both control and kindled GCs upon loading the neurons with the exogenous Ca(2+)-chelator BAPTA. These experiments demonstrate a high correlation between the loss of CaBP and changes in Ca2+ current inactivation and are consistent with the hypothesis that CaBP contributes to the physiological Ca(2+)-buffering in mammalian neurons.}, Author = {K{\"o}hr, G. and Lambert, C. E. and Mody, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Epilepsy;10 Development;Calcium-Binding Protein, Vitamin D-Dependent;Research Support, Non-U.S. Gov't;Hippocampus;10 Hippocampus;Rats;Immunohistochemistry;Calcium Channels;In Vitro;Research Support, U.S. Gov't, P.H.S.;Kindling (Neurology);Egtazic Acid;Animals;Male;Rats, Inbred Strains;Neurons}, Medline = {92008423}, Nlm_Id = {0043312}, Number = {3}, Organization = {Department of Neurology and Neurological Sciences, Stanford University Medical Center, CA 94305.}, Pages = {543-51}, Pubmed = {1655508}, Title = {Calbindin-D28K (CaBP) levels and calcium currents in acutely dissociated epileptic neurons}, Uuid = {F84C899D-B7B4-41E2-ADAF-CB95A71E05E4}, Volume = {85}, Year = {1991}} @article{Kosel:1997, Abstract = {Six cases of middle cerebral artery occlusion are presented in which the cellular changes accompanying descending degeneration of the lateral corticospinal tract were studied at different time points (5 days-10 years) following the insult. Microglia and perivascular cells were found to ingest large amounts of myelin degradation products, while expressing high levels of major histocompatibility complex (MHC) class II molecules. Activation of perivascular macrophages, as indicated by increased class II expression, lasted for many years and appeared to follow down-regulation of both phagocytic activity and class II expression on parenchymal microglia. TUNEL labeling was absent from both microglia and perivascular cells at all time points investigated. Indirect evidence is presented that microglia may transfer myelin degradation products to the perivascular space. Perivascular cells which express MHC class II molecules constitutively do not appear to leave the perivascular compartment in large numbers and could release myelin degradation products into the cerebrospinal fluid. The possible immunological consequences of these findings are discussed with respect to their possible relevance for antigen presentation and autoimmune central nervous system disease.}, Author = {K{\"o}sel, S. and Egensperger, R. and Bise, K. and Arbogast, S. and Mehraein, P. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Myelin Sheath;Humans;Macrophages;Middle Aged;Brain;Microglia;Female;11 Glia;Cerebrovascular Disorders;Male;Spinal Cord;Aged;Wallerian Degeneration;Aged, 80 and over;Arterial Occlusive Diseases;Adult;Cerebral Arterial Diseases;Histocompatibility Antigens Class II;Lipids}, Medline = {98106759}, Month = {12}, Nlm_Id = {0412041}, Number = {6}, Organization = {Molecular Neuropathology Laboratory, Institute of Neuropathology, Ludwig-Maximilians University, Munich, Germany.}, Pages = {532-8}, Pubmed = {9444354}, Title = {Long-lasting perivascular accumulation of major histocompatibility complex class II-positive lipophages in the spinal cord of stroke patients: possible relevance for the immune privilege of the brain}, Uuid = {B75097E0-E4E7-4805-BC61-AE465760BB0F}, Volume = {94}, Year = {1997}} @article{Kraemer:2001, Abstract = {Cortical migration disorders are a major cause for intractable epilepsy syndromes. High resolution MRI and PET are increasingly capable to identify cortical dysgenesis. In this study we used the rat freeze lesion model to investigate cortical morphological and functional changes in adult rats after induction of a cortical freeze lesion at postnatal day (p) 0. Autoradiographic measurements of basic cortical [14C]deoxyglucose metabolism showed a significant reduction up to 1 mm lateral to the lesion but no remote changes. Electrophysiological in vitro recordings revealed a significant reduction in the amplitude of stimulus-evoked field potential responses recorded lateral to the lesion as compared to medial recording sites. Our data provide further evidence that spatially restricted developmental alterations of cortical morphology cause functional changes in surrounding and histologically normal areas that need to be considered for a better understanding of the resulting pathophysiology.}, Author = {Kraemer, M. and Roth-Haerer, A. and Bruehl, C. and Luhmann, H. J. and Witte, O. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Cell Differentiation;Animals;Rats;21 Epilepsy;Neocortex;Denervation;Epilepsy;Cell Movement;Rats, Wistar;Glucose;Deoxyglucose;Organ Culture Techniques;Disease Models, Animal;Carbon Radioisotopes;Animals, Newborn;Nerve Net;Nervous System Malformations;21 Neurophysiology;Freezing;Neurons;Membrane Potentials;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {21329654}, Month = {7}, Nlm_Id = {9100935}, Number = {9}, Organization = {Neurologische Klinik, Heinrich-Heine-Universit{\"a}t, Moorenstr.5, D-40225 D{\"u}sseldorf, Germany.}, Pages = {2001-6}, Pubmed = {11435937}, Title = {Metabolic and electrophysiological alterations in an animal model of neocortical neuronal migration disorder}, Uuid = {34011F5B-E90D-4262-9EC7-4665FFED593C}, Volume = {12}, Year = {2001}} @article{Krall:1994, Abstract = {Gaucher disease is an inherited lysosomal storage disease in which the loss in functional activity of glucocerebrosidase (GC) results in the storage of its lipid substrate in cells of the macrophage lineage. A gene therapy approach involving retroviral transduction of autologous bone marrow (BM) followed by transplantation has been recently approved for clinical trial. Amelioration of the disease symptoms may depend on the replacement of diseased macrophages with incoming cells expressing human GC; however, the processes of donor cell engraftment and vector gene expression have not been addressed at the cellular level in relevant tissues. Therefore, we undertook a comprehensive immunohistologic study of macrophage and microglia replacement after murine BM transplantation with retrovirus-marked BM. Serial quantitative PCR analyses were employed to provide an overview of the time course of engraftment of vector-marked cells in a panel of tissues. Following reconstitution of hematopoietic tissues with vector-marked donor cells at early stages, GC+ cells began to infiltrate the liver, lung, brain, and spinal cord by 3 months after transplant. Immunohistochemical analyses of PCR+ tissues using the 8E4 monoclonal antibody specific for human GC revealed that macrophages expressing human GC had partially reconstituted the Mac-1+ population in all tissues in a manner characteristic to each tissue type. In the brain, 20\%of the total microglia had been replaced with donor cells expressing GC by 3 to 4 months after transplant. The finding that significant numbers of donor cells expressing a retroviral gene product immigrate to the central nervous system suggests that gene therapy for neuronopathic forms of lysosomal storage diseases as well as antiviral gene therapy for AIDS may be feasible.}, Author = {Krall, W. J. and Challita, P. M. and Perlmutter, L. S. and Skelton, D. C. and Kohn, D. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Genetic Markers;Animals;Humans;Macrophages;Bone Marrow Transplantation;Brain;Microglia;Mice, Inbred C57BL;Retroviridae;11 Glia;Male;Genetic Vectors;Research Support, U.S. Gov't, P.H.S.;Glucosylceramidase;Polymerase Chain Reaction;Mice;Immunohistochemistry;Gene Expression;Spleen;Research Support, Non-U.S. Gov't}, Medline = {94220722}, Month = {5}, Nlm_Id = {7603509}, Number = {9}, Organization = {Division of Research Immunology and Bone Marrow Transplantation, Childrens Hospital, Los Angeles, CA 90027.}, Pages = {2737-48}, Pubmed = {8167352}, Title = {Cells expressing human glucocerebrosidase from a retroviral vector repopulate macrophages and central nervous system microglia after murine bone marrow transplantation}, Uuid = {CCE6B77F-F08D-498C-8418-609114046F07}, Volume = {83}, Year = {1994}} @article{Krantic:2005, Abstract = {Rapid progress in understanding the molecular basis of neurodegeneration has been tightly linked with recent discoveries in the field of programmed cell death (PCD). Analysis of PCD in neuronal demise has led to identification of several associated phenomena, such as re-initiation of the cell cycle and the key role of oxidative stress, although putative causal relationships between these events are still debatable. These issues are reviewed here in the context of acute and chronic neurodegenerative processes. In addition, newly emerging concepts concerning cell-cycle re-initiation are discussed in terms of their potential impact on the development of more effective therapeutic strategies.}, Author = {Krantic, Slavica and Mechawar, Naguib and Reix, St{\'e}phanie and Quirion, R{\'e}mi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Aging;Neurons;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;07 Excitotoxicity Apoptosis;Neurodegenerative Diseases;Reactive Oxygen Species;Apoptosis;Models, Neurological;Cell Cycle;Humans;Brain;Animals;Oxidative Stress;review}, Month = {12}, Nlm_Id = {7808616}, Number = {12}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e (INMED), Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM), Parc Scientifique Luminy, BP13, 13 273 Marseille, France. krantic\@inmed.univ.mrs.fr}, Pages = {670-6}, Pii = {S0166-2236(05)00259-6}, Pubmed = {16216345}, Title = {Molecular basis of programmed cell death involved in neurodegeneration}, Uuid = {194E8C79-FBF9-43DD-9C86-A921F0D6F2A7}, Volume = {28}, Year = {2005}, url = {papers/Krantic_TrendsNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2005.09.011}} @article{Kreiman:2004, Abstract = {Sequence information and high-throughput methods to measure gene expression levels open the door to explore transcriptional regulation using computational tools. Combinatorial regulation and sparseness of regulatory elements throughout the genome allow organisms to control the spatial and temporal patterns of gene expression. Here we study the organization of cis-regulatory elements in sets of co-regulated genes. We build an algorithm to search for combinations of transcription factor binding sites that are enriched in a set of potentially co-regulated genes with respect to the whole genome. No knowledge is assumed about involvement of specific sets of transcription factors. Instead, the search is exhaustively conducted over combinations of up to four binding sites obtained from databases or motif search algorithms. We evaluate the performance on random sets of genes as a negative control and on three biologically validated sets of co-regulated genes in yeasts, flies and humans. We show that we can detect DNA regions that play a role in the control of transcription. These results shed light on the structure of transcription regulatory regions in eukaryotes and can be directly applied to clusters of co-expressed genes obtained in gene expression studies. Supplementary information is available at http://www.mit.edu/ approximately kreiman/resources/cisregul/.}, Author = {Kreiman, Gabriel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1362-4962}, Journal = {Nucleic Acids Res}, Keywords = {Computational Biology;10 Development;research support, non-u.s. gov't;Binding Sites;Response Elements;Algorithms;Gene Expression Regulation;Saccharomyces cerevisiae;Drosophila melanogaster;evaluation studies;Cell Cycle;Animals;Humans;24 Pubmed search results 2008;Muscle, Skeletal;Transcription Factors}, Nlm_Id = {0411011}, Number = {9}, Organization = {Center for Biological and Computational Learning, McGovern Institute for Brain Research, Massachusetts Institute of Technology, 45 Carleton Street, MIT E25-201B, Cambridge, MA 02142, USA. kreiman\@mit.edu}, Pages = {2889-900}, Pii = {32/9/2889}, Pubmed = {15155858}, Title = {Identification of sparsely distributed clusters of cis-regulatory elements in sets of co-expressed genes}, Uuid = {78EF4B19-D067-40ED-B975-DC81187CFDA5}, Volume = {32}, Year = {2004}, url = {papers/Kreiman_NucleicAcidsRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/nar/gkh614}} @article{Kreutzberg:1989, Abstract = {Following axonal interruption, structural, metabolic and physiological parameters change in motorneurons. Also, glial cells are involved in this process. Microglia proliferate and express new proteins such as vimentin or MHC antigens. Astrocytes show hypertrophy, increased GFAP synthesis, and formation of lamellae. Both glial cell types participate in deafferentation and insulation of regenerating neurons, a process with significance for post-lesioning functional impairment.}, Author = {Kreutzberg, G. W. and Graeber, M. B. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0885-7490}, Journal = {Metab Brain Dis}, Keywords = {Neuroglia;Motor Neurons;Nerve Regeneration;Not relevant;11 Glia;review, tutorial;Animals;review}, Medline = {89201129}, Month = {3}, Nlm_Id = {8610370}, Number = {1}, Organization = {Department of Neuromorphology, Max Planck Institute for Psychiatry, Planegg-Martinsried, F.R.G.}, Pages = {81-5}, Pubmed = {2649780}, Title = {Neuron-glial relationship during regeneration of motorneurons}, Uuid = {DB0C68DC-6D86-4B68-B4DA-8D2DDCFF87AA}, Volume = {4}, Year = {1989}} @article{Kriegstein:2005, Abstract = {Our knowledge of the proliferation, migration, and differentiation of neurons has changed dramatically over the last 10 years. Whereas traditionally it was thought that glial and neuronal cells were separate cell lines with different lineages, we now know that this is not true. Radial glia are a type of neural stem cell that generate excitatory pyramidal neurons directly through asymmetric cell division in the ventricular zone (VZ) of the telencephalon and indirectly through the symmetric division of daughter intermediate precursor cells that divide in the subventricular zone (SVZ). Moreover, pyramidal neurons, once thought to migrate only along radial guide fibers to the developing layers of the cortex, have been shown to proceed through four distinct stages of migration during which they change shape, direction, and speed. Gamma-aminobutyric acid (GABAergic) inhibitory interneurons, on the other hand, are generated not in the cortex, but in the medial ganglionic eminence and migrate tangentially to their final cortical destinations. Evidence suggests that GABA activation may play a role in coordinating the generation and migration of both pyramidal and interneuron populations. At the end of neurogenesis, radial glial cells translocate to the cortex and transform into astrocytes. Although they do not actively divide in the adult brain, astrocytes may retain the potential to generate new neurons. These new findings have increased our understanding of the mechanisms underlying certain developmental disorders and, in doing so, reveal potentially useful modes of therapeutic intervention.}, Author = {Kriegstein, Arnold R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Epilepsy;10 Development;Neuroglia;Research Support, Non-U.S. Gov't;Pyramidal Cells;Models, Neurological;Astrocytes;Cell Division;Neocortex;Stem Cells;Interneurons;gamma-Aminobutyric Acid;Humans;Cell Movement;Neurons}, Nlm_Id = {2983306R}, Organization = {Department of Neurology, University of California, San Francisco, San Francisco, California 94143, USA. kreigstein\@stemcell.ucsf.edu}, Pages = {15-21}, Pii = {EPI304}, Pubmed = {16201991}, Title = {Constructing circuits: neurogenesis and migration in the developing neocortex}, Uuid = {1556314C-B609-4380-8BCF-65E9BD7E6B2F}, Volume = {46 Suppl 7}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1528-1167.2005.00304.x}} @article{Kriegstein:2004, Abstract = {Real-time imaging of migrating neurons has changed our understanding of how newborn neurons reach their final positions in the developing cerebral cortex. The migratory routes and modes of migration are more diverse and complex than previously thought. The finding that cortical interneurons migrate to the cortex from origins in the ventral telencephalon has already markedly altered our view of cortical migration. More recent findings have demonstrated additional nuances in the migratory pattern and highlighted differences between subsets of interneurons. Moreover, radial migration of pyramidal neurons does not progress smoothly from ventricle to cortical plate, but is instead characterized by distinct migratory phases in which neurons change shape and direction of movement. Integrating these findings with the molecular machinery underlying migration will provide a more complete picture of how the cerebral cortex is assembled.}, Author = {Kriegstein, Arnold R. and Noctor, Stephen C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {review;10 Development;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, P.H.S.;Humans;Animals;Cerebral Cortex;Neurons;Cell Movement}, Month = {7}, Nlm_Id = {7808616}, Number = {7}, Organization = {Department of Neurology, Columbia University Medical Center, New York, NY 10032, USA. ark17\@columbia.edu}, Pages = {392-9}, Pii = {S0166223604001547}, Pubmed = {15219738}, Title = {Patterns of neuronal migration in the embryonic cortex}, Uuid = {0010FB9D-AEFC-46E8-A02D-59AB1B432A7A}, Volume = {27}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2004.05.001}} @article{Krishna-K:2008, Abstract = {Cadherins are superfamily of Ca(2+)-dependent transmembrane glycoproteins with more than 100 members. They play a role in a wide variety of developmental mechanisms, including cell proliferation, cell differentiation, cell-cell recognition, neurite outgrowth and synaptogenesis. We cloned 16 novel members of the classic cadherin and delta-protocadherin subgroups from ferret brain. Their expression patterns were investigated by in situ hybridization in the developing primary visual cortex (V1) of the ferret. Fifteen out of the 16 cadherins are expressed in a spatiotemporally restricted fashion throughout development. Each layer of V1 can be characterized by the combinatorial expression of a subset of cadherins at any given developmental stage. A few cadherins are expressed by subsets of neurons in specific layers or by neurons dispersed throughout all cortical layers. Generally, the expression of protocadherins is more widespread, whereas that of classic cadherins is more restricted to specific layers. At the V1/V2 boundary, changes in layer-specific cadherin expression are observed. In conclusion, our results suggest that cadherins provide a code of potentially adhesive cues for layer formation in ferret V1. The persistence of expression in the adult suggests a functional role also in the mature cortex.}, Author = {Krishna-K and Nuernberger, and Weth, and Redies,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1460-2199}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {9110718}, Organization = {Institute of Anatomy I.}, Pii = {bhn090}, Pubmed = {18534988}, Title = {Layer-Specific Expression of Multiple Cadherins in the Developing Visual Cortex (V1) of the Ferret}, Uuid = {BD38DECA-BD3B-4ED2-B6CC-D16BC14AB947}, Year = {2008}, url = {papers/Krishna-K_CerebCortex2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhn090}} @article{Kristan:2006, Abstract = {'Form follows function' is an architectural philosophy attributed to the great American architect Louis Sullivan , and later taken up by the Bauhaus movement. It stresses that the form of a building should reflect its function. Neuroscientists have used the connverse of this dictum to learn the functions of neural circuits, believing that if we study neural architecture, it will lead us to an understanding of how neural systems function. New tools for studying the structure of neural circuits are being developed, so it is important to discuss what the old techniques have taught us about how to derive function from the form of a neural circuit.}, Author = {Kristan, William B. and Katz, Paul}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9107782}, Number = {19}, Organization = {University of California San Diego, Division of Biological Sciences, Neurobiology Section, 9500 Gilman Drive, La Jolla, California 92093-0357, USA.}, Pages = {R828-31}, Pii = {S0960-9822(06)02146-4}, Pubmed = {17027473}, Title = {Form and function in systems neuroscience}, Uuid = {A9A134FD-B2AF-4BC1-ABFE-0F9DE10B5E12}, Volume = {16}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2006.08.079}} @article{Kristensen:2003, Abstract = {The microtubule-disrupting agent colchicine is known to be particular toxic for certain types of neurons, including the granule cells of the dentate gyrus. In this study we investigated whether colchicine could induce such neuron-specific degeneration in developing (1 week in vitro) and mature (3 weeks in vitro) organotypic hippocampal slice cultures and whether the induced cell death was apoptotic and/or necrotic. When applied to 1-week-old cultures for 48 h, colchicine induced primarily apoptotic, but also a minor degree of necrotic cell death in the dentate granule cells, as investigated by cellular uptake of the fluorescent dye propidium iodide (PI), immunostaining for active caspase 3 and c-Jun/AP-1 (N) and fragmentation of nuclei as seen in Hoechst 33342 staining. All four markers appeared after 12 h of colchicine exposure. Two of them, active caspase 3 and c-Jun/AP-1 (N) displayed a similar time course and reached a maximum after 24 h of exposure, 24 h ahead of both PI uptake and Hoechst 33342 staining, which together displayed similar time profiles and a close correlation. In 3-week-old cultures, colchicine did not induce apoptotic or necrotic cell death. Attempts to interfere with the colchicine-induced apoptosis in 1-week-old cultures showed that colchicine-induced PI uptake and formation of apoptotic nuclei were temporarily prevented by coapplication of the protein synthesis inhibitor cycloheximide. Application of the pancaspase inhibitor z-VAD-fmk almost completely abolished the formation of active caspase 3 protein and apoptotic nuclei induced by colchicine, but the formation of necrotic nuclei increased correspondingly and the PI uptake was unaffected. We conclude that colchicine induces caspase 3-dependent apoptotic cell death of dentate granule cells in hippocampal brain slice cultures, but the apoptotic cell death is highly dependent on the developmental stage of the cultures. 0006-8993 Journal Article}, Author = {Kristensen, B. W. and Noer, H. and Gramsbergen, J. B. and Zimmer, J. and Noraberg, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Brain Res}, Keywords = {Fluorescent Dyes/diagnostic use;Dose-Response Relationship, Drug;Neurotoxins/*toxicity;Caspases/drug effects/metabolism;Animals;Rats;Benzimidazoles/diagnostic use;Cycloheximide/pharmacology;EE pdf;Rats, Wistar;Neuroprotective Agents/pharmacology;08 Aberrant cell cycle;Time Factors;Apoptosis/*drug effects;Dentate Gyrus/*drug effects/metabolism;Support, Non-U.S. Gov't;Colchicine/*toxicity;Protein Synthesis Inhibitors/pharmacology;Neurons/*drug effects/metabolism;Immunohistochemistry;Necrosis;Amino Acid Chloromethyl Ketones/pharmacology;Propidium/metabolism}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark, Winslowparken 21, DK-5000 C, Odense, Denmark. bkristensen\@health.sdu.dk}, Pages = {264-78}, Title = {Colchicine induces apoptosis in organotypic hippocampal slice cultures}, Uuid = {4D76C49D-FB61-4229-9F3E-4ADD85218810}, Volume = {964}, Year = {2003}, url = {papers/Kristensen_BrainRes2003}} @article{Krivit:1995, Abstract = {Treatment and potential cure of lysosomal and peroxisomal diseases, heretofore considered fatal, has become a reality during the past decade. Bone marrow transplantation, (BMT), has provided a method for replacement of the disease-causing enzyme deficiency. Cells derived from the donor marrow continue to provide enzyme indefinitely. Several scores of patients with diseases as diverse as metachromatic leukodystrophy, adrenoleukodystrophy, globoid cell leukodystrophy, Hurler syndrome (MPS I-H), Maroteaux-Lamy (MPS VI) Gaucher disease, and fucosidosis have been successfully treated following long-term engraftment. Central nervous system (CNS) manifestations are also prevented or ameliorated in animal models of these diseases following engraftment from normal donors. The microglial cell system has been considered to be the most likely vehicle for enzyme activity following bone marrow engraftment. Microglia in the mature animal or human are derived from the newly engrafted bone marrow. Graft-v-host disease activation of the microglia is also of importance. This article will summarize some of the pertinent literature relative to the role of microglia in such transplant processes.}, Author = {Krivit, W. and Sung, J. H. and Shapiro, E. G. and Lockman, L. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0963-6897}, Journal = {Cell Transplant}, Keywords = {Phagocytosis;Animals;Humans;Lysosomal Storage Diseases;Bone Marrow Transplantation;review, tutorial;Peroxisomal Disorders;review;Microglia;Female;Cell Movement;11 Glia;Male;Blood-Brain Barrier;Bone Marrow Cells;Cell Lineage;Research Support, U.S. Gov't, P.H.S.;Graft vs Host Disease;Central Nervous System}, Medline = {96090321}, Nlm_Id = {9208854}, Number = {4}, Organization = {Department of Pediatrics, University of Minnesota Medical School, Minneapolis 55455, USA.}, Pages = {385-92}, Pii = {096368979500021O}, Pubmed = {7582569}, Title = {Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases}, Uuid = {BF60B3F9-CB4A-438B-A7A8-BBA7316F8E48}, Volume = {4}, Year = {1995}} @article{Kronenberg:2003, Abstract = {To study how adult hippocampal neurogenesis might originate from the proliferation of stem or progenitor cells in vivo, we have used transgenic mice expressing green fluorescent protein (GFP) under the nestin promoter to identify these cells. Having described an astrocyte-like type 1 cell with low proliferative activity, a characteristic morphology, vascular end feet, and passive electrophysiological properties, we focused here on the large population of nestin-GFP-expressing type 2 cells, which lack all these features. Type 2 cells were highly proliferative and showed signs suggestive of their involvement in the neuronal lineage. They could be subclassified by the absence (type 2a) or presence (type 2b) of a coexpression of the early neuronal marker doublecortin. A third type of proliferating cells was doublecortin positive but nestin-GFP negative (type 3). We believe that type 2a, 2b, and 3 cells mirror a marker progression during earliest neuronal development. This view is supported by the increasing coexpression of the early granule cell-specific marker Prox-1. The low proliferative activity of type 1 cells showed little change over time or under "neurogenic interventions,"such as a challenge by environmental complexity (ENR) or voluntary physical activity (RUN). However, RUN led to a significant increase of type 2 cells labeled with the proliferation marker bromodeoxyuridine (BrdU). ENR did not cause increased cell proliferation or an increased number of BrdU-labeled type 2 cells, but both ENR and RUN resulted in more newly generated cells lacking nestin-GFP immunoreactivity and expressing Prox-1. These findings allow us to break down what was broadly perceived as "proliferation"in earlier experiments into the relative contribution of several cell types, representing the earliest steps of neuronal development. 0021-9967 Journal Article}, Author = {Kronenberg, G. and Reuter, K. and Steiner, B. and Brandt, M. D. and Jessberger, S. and Yamaguchi, M. and Kempermann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {J Comp Neurol}, Keywords = {Intermediate Filament Proteins/genetics/metabolism;Animals;Random Allocation;Comparative Study;Neural Cell Adhesion Molecule L1/metabolism;02 Adult neurogenesis migration;Mice, Transgenic;*Environment;Mice, Inbred C57BL;Motor Activity/physiology;Time Factors;Behavior, Animal;Neurons/classification/*physiology;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;BB pdf;Sialic Acids/metabolism;Homeodomain Proteins/metabolism;Ki-67 Antigen/metabolism;Hippocampus/*cytology/growth &development;Neuropeptides/metabolism;Mice;Cell Division;Immunohistochemistry;Bromodeoxyuridine/pharmacokinetics;Luminescent Proteins/genetics/metabolism}, Number = {4}, Organization = {Max Delbruck Center for Molecular Medicine (MDC) Berlin-Buch, 13125 Berlin, Germany.}, Pages = {455-63}, Pubmed = {14624480}, Title = {Subpopulations of proliferating cells of the adult hippocampus respond differently to physiologic neurogenic stimuli}, Uuid = {60780499-018E-4790-A453-31403D150336}, Volume = {467}, Year = {2003}, url = {papers/Kronenberg_JCompNeurol2003.pdf}} @article{Krubitzer:1995, Abstract = {The present investigation was designed to determine the number and internal organization of somatosensory fields in monotremes. Microelectrode mapping methods were used in conjunction with cytochrome oxidase and myelin staining to reveal subdivisions and topography of somatosensory cortex in the platypus and the short-billed echidna. The neocortices of both monotremes were found to contain four representations of the body surface. A large area that contained neurons predominantly responsive to cutaneous stimulation of the contralateral body surface was identified as the primary somatosensory area (SI). Although the overall organization of SI was similar in both mammals, the platypus had a relatively larger representation of the bill. Furthermore, some of the neurons in the bill representation of SI were also responsive to low amplitude electrical stimulation. These neurons were spatially segregated from neurons responsive to pure mechanosensory stimulation. Another somatosensory field (R) was identified immediately rostral to SI. The topographic organization of R was similar to that found in SI; however, neurons in R responded most often to light pressure and taps to peripheral body parts. Neurons in cortex rostral to R were responsive to manipulation of joints and hard taps to the body. We termed this field the manipulation field (M). The mediolateral sequence of representation in M was similar to that of both SI and R, but was topographically less precise. Another somatosensory field, caudal to SI, was adjacent to SI laterally at the representation of the face, but medially was separated from SI by auditory cortex. Its position relative to SI and auditory cortex, and its topographic organization led us to hypothesize that this caudal field may be homologous to the parietal ventral area (PV) as described in other mammals. The evidence for the existence of four separate representations in somatosensory cortex in the two species of monotremes indicates that cortical organization is more complex in these mammals than was previously thought. Because the two monotreme families have been separate for at least 55 million years (Richardson, B.J. [1987] Aust. Mammal. 11:71-73), the present results suggest either that the original differentiation of fields occurred very early in mammalian evolution or that the potential for differentiation of somatosensory cortex into multiple fields is highly constrained in evolution, so that both species arrived at the same solution independently. 0021-9967 Journal Article}, Author = {Krubitzer, L. and Manger, P. and Pettigrew, J. and Calford, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Comp Neurol}, Keywords = {Electric Stimulation;19 Neocortical evolution;Parietal Lobe/anatomy &histology/physiology;Visual Cortex/anatomy &histology/physiology;Physical Stimulation;Models, Neurological;Auditory Cortex/anatomy &histology/physiology;Platypus/*anatomy &histology;N;Echidna/*anatomy &histology;Animals;Somatosensory Cortex/*anatomy &histology/physiology;Support, Non-U.S. Gov't;Microelectrodes;Receptors, Sensory/physiology}, Number = {2}, Organization = {Department of Physiology and Pharmacology, University of Queensland, Australia.}, Pages = {261-306}, Pubmed = {7699113}, Title = {Organization of somatosensory cortex in monotremes: in search of the prototypical plan}, Uuid = {EB3AF88F-11EA-4FD7-87B7-37B3E7BBF547}, Volume = {351}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7699113}} @article{Krueger:1987, Abstract = {Normal and malignant cells show differences in cell membrane lipid fluidity (CMF) which influence the expression of membrane receptors and may interfere with cell function. Friend virus (FLV) and Moloney virus (MLV) infected hematopoietic and lymphoid cells were monitored for CMF (fluorescence polarization) and for transferrin (TFC) and thymic (Thy) receptors (FITC-labelled monoclonal antibodies). CMF was modulated with cholesterol hemisuccinate (CHS), phospholipids (PL) and DMSO. Erythropoietic stem cells exhibit an increased persistent CMF within minutes after FLV infection; transferrin receptors are expressed, yet no hemoglobin is synthesized. CHS rigidification reduces TFC expression with differentiation of cells and hemoglobin synthesis, yet transformed cell populations do not react uniformly. Thymic lymphocytes, instead, do not exhibit changes in Thy expression upon CHS treatment although cell membranes become rigidified. Separate experiments showed these cells not being "transformed"per se but blocked in differentiation because of viral destruction of thymic epithelial cells with loss of thymopoietin in vivo. Thus viral cell transformation is followed by non-rigid but persistent membrane fluidization interfering with only selective receptor expression. 0258-851x Journal Article}, Author = {Krueger, G. R. and Stolzenburg, T. and Muller, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {In Vivo}, Keywords = {EE, DMSO, abstr;Leukemia, Experimental/genetics/*physiopathology;08 Aberrant cell cycle;Moloney murine leukemia virus/*genetics;*Cell Transformation, Neoplastic;*Membrane Fluidity;Friend murine leukemia virus/*genetics;Animals, Newborn;Receptors, Transferrin/*metabolism;Animals;Support, Non-U.S. Gov't;Mice;Mice, Inbred Strains}, Number = {6}, Organization = {Pathology Institute, University of Cologne, F.R.G.}, Pages = {343-6}, Pubmed = {2979801}, Title = {Cell membrane lipid fluidity and receptor expression in Moloney- and Friend virus-transformed cells}, Uuid = {15D7A82E-7FAC-49A1-A097-146BCA0B75C9}, Volume = {1}, Year = {1987}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2979801}} @article{Kruger:1996, Abstract = {Cortical spreading depression (SD) represents a pathophysiological signal that has been associated with the induction of migraine and ischaemic brain damage. The properties of repetitive SDs and their effects on excitatory and inhibitory synaptic transmission were analysed in neocortical slices obtained from adult rats. The SD showed only small variations in amplitude, duration and integral when elicited four times at intervals of 30 min. Extracellularly recorded paired pulse inhibition was, however, significantly reduced by approximately 10\%with each SD episode. Since excitatory synaptic transmission was unaffected, our data indicate that repetitive SD causes a selective reduction of intracortical inhibition.}, Author = {Kr{\"u}ger, H. and Luhmann, H. J. and Heinemann, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {21 Epilepsy;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Rats, Wistar;Synaptic Transmission;gamma-Aminobutyric Acid;Animals;Cerebral Cortex;Spreading Cortical Depression;24 Pubmed search results 2008}, Medline = {97135920}, Month = {11}, Nlm_Id = {9100935}, Number = {15-17}, Organization = {Institute of Physiology at the Charit{\'e}, Department of Neurophysiology, Berlin, Germany.}, Pages = {2733-6}, Pubmed = {8981457}, Title = {Repetitive spreading depression causes selective suppression of GABAergic function}, Uuid = {0D57891A-748F-40ED-9F83-B7376F167355}, Volume = {7}, Year = {1996}} @article{Kuan:2004, Abstract = {Recent studies suggest that postmitotic neurons can reenter the cell cycle as a prelude to apoptosis after brain injury. However, most dying neurons do not pass the G1/S-phase checkpoint to resume DNA synthesis. The specific factors that trigger abortive DNA synthesis are not characterized. Here we show that the combination of hypoxia and ischemia induces adult rodent neurons to resume DNA synthesis as indicated by incorporation of bromodeoxyuridine (BrdU) and expression of G1/S-phase cell cycle transition markers. After hypoxia-ischemia, the majority of BrdU- and neuronal nuclei (NeuN)-immunoreactive cells are also terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL)-stained, suggesting that they undergo apoptosis. BrdU+ neurons, labeled shortly after hypoxia-ischemia, persist for >5 d but eventually disappear by 28 d. Before disappearing, these BrdU+/NeuN+/TUNEL+ neurons express the proliferating cell marker Ki67, lose the G1-phase cyclin-dependent kinase (CDK) inhibitors p16INK4 and p27Kip1 and show induction of the late G1/S-phase CDK2 activity and phosphorylation of the retinoblastoma protein. This contrasts to kainic acid excitotoxicity and traumatic brain injury, which produce TUNEL-positive neurons without evidence of DNA synthesis or G1/S-phase cell cycle transition. These findings suggest that hypoxia-ischemia triggers neurons to reenter the cell cycle and resume apoptosis-associated DNA synthesis in brain. Our data also suggest that the demonstration of neurogenesis after brain injury requires not only BrdU uptake and mature neuronal markers but also evidence showing absence of apoptotic markers. Manipulating the aberrant apoptosis-associated DNA synthesis that occurs with hypoxia-ischemia and perhaps neurodegenerative diseases could promote neuronal survival and neurogenesis.}, Author = {Kuan, Chia-Yi Y. and Schloemer, Aryn J. and Lu, Aigang and Burns, Kevin A. and Weng, Wei-Lan L. and Williams, Michael T. and Strauss, Kenneth I. and Vorhees, Charles V. and Flavell, Richard A. and Davis, Roger J. and Sharp, Frank R. and Rakic, Pasko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;08 Aberrant cell cycle;06 Adult neurogenesis injury induced}, Month = {11}, Nlm_Id = {8102140}, Number = {47}, Organization = {Department of Pediatrics, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. alex.kuan\@chmcc.org}, Pages = {10763-72}, Pii = {24/47/10763}, Pubmed = {15564594}, Title = {Hypoxia-ischemia induces DNA synthesis without cell proliferation in dying neurons in adult rodent brain}, Uuid = {325284AE-D395-11D9-A0E9-000D9346EC2A}, Volume = {24}, Year = {2004}, url = {papers/Kuan_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3883-04.2004}} @article{Kuenzel:1982, Abstract = {Six groups of broiler chicks, Gallus domesticus, sustained bilateral lesions to specific neural structures residing in the lateral hypothalamic and thalamic areas. In contrast to past data reported for the albino rat, the pigeon, Columba livia and barbary dove, Streptopelia risoria, bilateral destruction of the chick lateral hypothalamic area (LHy), quinto-frontal tract (QF), and stratum cellulare externum (SCE) resulted in transient aphagia and rapid recovery of lost body weight. Similarly, bilateral destruction of the nucleus reticularis superior (RS) and nucleus intercalatus (ICT) resulted in a temporary 1--3 day period of aphagia with body weight returning to pre-operative levels in approximately 4 days. Bilateral destruction of the ansa lenticularis (AL) resulted in a more prolonged period of aphagia (4 days) and an average 8-day period to recover lost body weight. Additional data suggest that more persistent aphagia can be induced following lesions to the posterior hypothalamus and midbrain. Specifically, bilateral lesions which destroyed the following combination of neural structures resulted in prolonged aphagia: AL, QF and posterior LHy; AL and posterior nucleus of the AL (ALp); and AL, ALp and QF. It is suggested that the AL and ALp contain neurons which are part of a more complex system that modulates or controls motor activity and feeding behavior in birds.}, Author = {Kuenzel, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:34 -0400}, Issn = {0031-9384}, Journal = {Physiol Behav}, Keywords = {24 Pubmed search results 2008;Brain Stem;Mesencephalon;Eating;Research Support, Non-U.S. Gov't;Hypothalamus;Neural Pathways;Corpus Striatum;Body Weight;Chickens;Male;Brain;Animals;Frontal Lobe}, Medline = {82197973}, Month = {2}, Nlm_Id = {0151504}, Number = {2}, Pages = {237-44}, Pubmed = {7079336}, Title = {Transient aphagia produced following bilateral destruction of the lateral hypothalamic area and quinto-frontal tract of chicks}, Uuid = {B66EFA4E-3EE3-4354-8265-5D83398DE9CD}, Volume = {28}, Year = {1982}} @article{Kuhn:1996, Abstract = {The hippocampus is one of the few areas of the rodent brain that continues to produce neurons postnatally. Neurogenesis reportedly persists in rats up to 11 months of age. Using bromodeoxyuridine (BrdU) labeling, the present study confirms that in the adult rat brain, neuronal progenitor cells divide at the border between the hilus and the granule cell layer (GCL). In adult rats, the progeny of these cells migrate into the GCL and express the neuronal markers NeuN and calbindin-D28k. However, neurogenesis was drastically reduced in aged rats. Six-to 27-month-old Fischer rats were injected intraperitoneally with BrdU to detect newborn cells in vivo and to follow their fate in the dentate gyrus. When killed 4-6 weeks after BrdU labeling, 12- to 27- month-old rats exhibited a significant decline in the density of BrdU- positive cells in the granule cell layer compared with 6-month-old controls. Decreased neurogenesis in aging rats was accompanied by reduced immunoreactivity for poly-sialylated neural cell adhesion molecule, a molecule that is involved in migration and process elongation of developing neurons. When animals were killed immediately (12 hr) after BrdU injection, significantly fewer labeled cells were observed in the GCL and adjacent subgranular zone of aged rats, indicative of a decrease in mitotic activity of neuronal precursor cells. The reduced proliferation was not attributable to a general aged- related metabolic impairment, because the density of BrdU-positive cells was not altered in other brain regions with known mitotic activity (e.g., hilus and lateral ventricle wall). The decline in neurogenesis that occurs throughout the lifespan of an animal can thus be related to a decreasing proliferation of granule cell precursors.}, Author = {Kuhn, H. G. and Dickinson-Anson, H. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {J Neurosci}, Keywords = {Neural Cell Adhesion Molecules/analysis;Rats;Comparative Study;Sialic Acids/analysis;Female;Neurons/chemistry/*cytology;Animal;Polysaccharides/analysis;Aging/*physiology;Stem Cells/*cytology;Dentate Gyrus/*cytology;01 Adult neurogenesis general;Rats, Inbred F344;Support, Non-U.S. Gov't;Cell Division/physiology;A-7;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Cell Differentiation/physiology;Immunohistochemistry;Bromodeoxyuridine;Biological Markers/analysis}, Number = {6}, Organization = {Laboratory of Genetics, Salk Institute, La Jolla, California 92037, USA.}, Pages = {2027-33.}, Title = {Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation}, Uuid = {6F91BFE5-4E8B-4F84-B75B-AB567B501497}, Volume = {16}, Year = {1996}, url = {papers/Kuhn_JNeurosci1996.pdf}} @article{Kuhn:1997, Abstract = {Neurons and glia are generated throughout adulthood from proliferating cells in two regions of the rat brain, the subventricular zone (SVZ) and the hippocampus. This study shows that exogenous basic fibroblast growth factor (FGF-2) and epidermal growth factor (EGF) have differential and site-specific effects on progenitor cells in vivo. Both growth factors expanded the SVZ progenitor population after 2 weeks of intracerebroventricular administration, but only FGF-2 induced an increase in the number of newborn cells, most prominently neurons, in the olfactory bulb, the normal destination for neuronal progenitors migrating from the SVZ. EGF, on the other hand, reduced the total number of newborn neurons reaching the olfactory bulb and substantially enhanced the generation of astrocytes in the olfactory bulb. Moreover, EGF increased the number of newborn cells in the striatum either by migration of SVZ cells or by stimulation of local progenitor cells. No evidence of neuronal differentiation of newborn striatal cells was found by three-dimensional confocal analysis, although many of these newborn cells were associated closely with striatal neurons. The proliferation of hippocampal progenitors was not affected by either growth factor. However, EGF increased the number of newborn glia and reduced the number of newborn neurons, similar to the effects seen in the olfactory bulb. These findings may be useful for elucidating the in vivo role of growth factors in neurogenesis in the adult CNS and may aid development of neuronal replacement strategies after brain damage.}, Author = {Kuhn, H. G. and Winkler, J. and Kempermann, G. and Thal, L. J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {J Neurosci}, Keywords = {Fibroblast Growth Factor, Basic/*pharmacology;Rats, Inbred F344;C-6;Stem Cells/*drug effects;Rats;Brain/*drug effects;Animal;Cell Count/*drug effects;Epidermal Growth Factor/*pharmacology;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Neurons/*drug effects;Male}, Number = {15}, Organization = {Laboratory of Genetics, The Salk Institute, La Jolla, California 92186, USA.}, Pages = {5820-9.}, Title = {Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain}, Uuid = {5880393F-DEE5-45DE-A02E-D286F91864A1}, Volume = {17}, Year = {1997}, url = {papers/Kuhn_JNeurosci1997.pdf}} @article{Kulkarni:1994, Abstract = {Little is known about the regulation of apoptosis in fibroblasts although several model systems including serum deprivation and treatment with staurosporine or topoisomerase inhibitors have been used to induce apoptosis in vitro. To validate a reproducible in vitro model for the study of apoptosis in fibroblasts, we cultured density-inhibited monolayer cultures of Balb/c 3T3 fibroblasts in Dulbecco's modified essential medium plus 15\%fetal calf serum and then withdrew serum. Time-lapse video microscopy demonstrated that within minutes of serum withdrawal, cells lost substrate attachment and floated to the top of the liquid growth medium. There was a time-dependent increase in the number of non-adherent cells. Some of these cells regained attachment and spread momentarily, but they eventually rounded up and lost attachment permanently. In contrast to serum-containing cultures in which similar morphological changes were followed by mitosis, in serum-free cultures repeated attempts at mitosis were followed by permanent attachment loss and presumably cell death. To assess whether all the non-adherent cells were in fact dead, the percentages of cells that continued to proliferate upon return to serum-supplemented conditions was computed. After various periods of serum starvation a decreasing proportion (approx. 75\%at 30 minutes; <2\%at 24 hours) of the non-adherent cells could be rescued by addition of serum. Transmission electron microscopy of cells 3 hours after serum withdrawal showed that the majority (approximately 60\%) of non-adherent cells exhibited marked intranuclear chromatin condensation but maintained integrity of cell and nuclear membranes and cell organelles, morphological changes consistent with those of apoptotic cell death. Scanning electron microscopy of cultures 3 hours following serum withdrawal showed rounded cells with marked surface blebbing. Fluorescence and confocal microscopy revealed increased intensity of nuclear staining with DAPI while actin filaments became indistinct or collapsed around the nucleus. After cycloheximide treatment to inhibit protein synthesis, there was no reduction of apoptosis. Gel electrophoresis of DNA from both control and 3 hour-serum-deprived cells showed intact DNA with no oligonucleosomal length fragmentation. After serum withdrawal, intracellular calcium was reduced by about 32\%over 5 minutes as measured by fura2 ratio fluorimetry in single cells. Serum-starved cells showed a time-dependent shrinkage in mean cell diameter compared to trypsinized, adherent control cells (at 0 hours, mean diameter = 18.0 microns--viable; at 4 hours, mean diameter = 15.5 microns--apoptotic). Flow cytometric analysis showed increased propidium iodide staining and reduced fluorescein diacetate uptake over 3 hours, changes that were contemporaneous with the reduction of cell diameter.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Kulkarni, G. V. and McCulloch, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0021-9533}, Journal = {J Cell Sci}, Keywords = {Microscopy, Phase-Contrast;Microscopy, Electron, Scanning;Animals;Electrophoresis, Agar Gel;07 Excitotoxicity Apoptosis;Cycloheximide;Apoptosis;Models, Biological;DNA;Mitosis;Genes, myc;Calcium;Microscopy, Fluorescence;Cell Adhesion;Support, Non-U.S. Gov't;3T3 Cells;Cell Size;Flow Cytometry;Mice;Microscopy, Electron;Culture Media;Gene Expression}, Medline = {95014779}, Month = {5}, Nlm_Id = {0052457}, Organization = {Faculty of Dentistry, University of Toronto, Ontario, Canada.}, Pages = {1169-79}, Pubmed = {7929626}, Title = {Serum deprivation induces apoptotic cell death in a subset of Balb/c 3T3 fibroblasts}, Uuid = {9F98B556-58F3-47CE-B12F-DEF9B50F7C53}, Volume = {107 ( Pt 5)}, Year = {1994}, url = {papers/Kulkarni_JCellSci1994.pdf}} @article{Kulkarni:2006, Abstract = {To evaluate the specificity of long dsRNAs used in high-throughput RNA interference (RNAi) screens performed at the Drosophila RNAi Screening Center (DRSC), we performed a global analysis of their activity in 30 genome-wide screens completed at our facility. Notably, our analysis predicts that dsRNAs containing >/=19-nucleotide perfect matches identified in silico to unintended targets may contribute to a significant false positive error rate arising from off-target effects. We confirmed experimentally that such sequences in dsRNAs lead to false positives and to efficient knockdown of a cross-hybridizing transcript, raising a cautionary note about interpreting results based on the use of a single dsRNA per gene. Although a full appreciation of all causes of false positive errors remains to be determined, we suggest simple guidelines to help ensure high-quality information from RNAi high-throughput screens.}, Author = {Kulkarni, and Booker, and Silver, and Friedman, and Hong, and Perrimon, and Mathey-Prevot,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {21 Neurophysiology;23 RNAi;24 Pubmed search results 2008;23 Technique}, Month = {10}, Nlm_Id = {101215604}, Number = {10}, Organization = {[1] Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. [2] Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA. [3] These authors contributed equally to this work.}, Pages = {833-838}, Pii = {nmeth935}, Pubmed = {16964256}, Title = {Evidence of off-target effects associated with long dsRNAs in Drosophila melanogaster cell-based assays}, Uuid = {FEC9BA6C-48A4-11DB-A317-000D9346EC2A}, Volume = {3}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth935}} @article{Kumar:2001, Abstract = {Despite the major role of excitatory cortico-cortical connections in mediating neocortical activities, little is known about these synapses at the cellular level. Here we have characterized the synaptic properties of long-range excitatory-to-excitatory contacts between visually identified layer V pyramidal neurons of agranular frontal cortex in callosally connected neocortical slices from postnatal day 13 to 21 (P13-21) rats. Midline stimulation of the corpus callosum with a minimal stimulation paradigm evoked inward excitatory postsynaptic currents (EPSCs) with an averaged peak amplitude of 56.5 +/- 5 pA under conditions of whole cell voltage clamp at -70 mV. EPSCs had fixed latencies from stimulus onset and could follow stimulus trains (1-20 Hz) without changes in kinetic properties. Bath application of 2,3-dihydro-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX) abolished these responses completely, indicating that they were mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs). Evoked responses were isolated in picrotoxin to yield purely excitatory PSCs, and a low concentration of NBQX (0.1 microM) was used to partially block AMPARs and prevent epileptiform activity in the tissue. Depolarization of the recorded pyramidal neurons revealed a late, slowly decaying component that reversed at approximately 0 mV and was blocked by D-2-amino-5-phosphonovaleric acid. Thus AMPA and N-methyl-D-aspartate receptors (NMDARs) coexist at callosal synapses and are likely to be activated monosynaptically. The peak amplitudes and decay time constants for EPSCs evoked using minimal stimulation (+/-40 mV) were similar to spontaneously occurring sEPSCs. Typical conductances associated with AMPA and NMDAR-mediated components, deduced from their respective current-voltage (I-V) relationships, were 525 +/- 168 and 966 +/- 281 pS, respectively. AMPAR-mediated responses showed age-dependent changes in the rectification properties of their I-V relationships. While I-Vs from animals >P15 were linear, those in the younger (3.0.CO;2-6}, Pubmed = {8929897}, Title = {Removal of cobalt-labeled neurons and nerve fibers by microglia from the frog's brain and spinal cord}, Uuid = {0AE0E1D7-2DEB-4AF6-A3CE-B86B46720271}, Volume = {16}, Year = {1996}} @article{Lazarowski:2006, Abstract = {Epileptogenic cortical tubers, characterized by dysplastic neurons and balloon cells, is a frequent feature of tuberous sclerosis. In severe tuberous sclerosis-affected individuals, seizures are refractory to medication. Multidrug resistance proteins (multidrug resistance protein-1 [MDR-1] and multidrug resistance-associated protein-1 [MRP-1]) have been found to be highly expressed in epileptogenic cortical tubers. However, two new proteins related to refractoriness in cancer (breast cancer resistance protein and major vault protein) have not been investigated in tuberous sclerosis and refractory epilepsy. On the same brain specimens previously describing the MDR-1 and MRP-1 expression, we investigated retrospectively breast cancer resistance protein and major vault protein by specific monoclonal antibodies and routine immunohistochemistry methods. Breast cancer resistance protein was present in vascular endothelial cells from all the vessels examined in 3 of 3 cases. Major vault protein was detected in only one case, and selectively expressed in several but not all ballooned cells. In epileptogenic cortical tubers, the additional expression of breast cancer resistance protein on vessels and major vault protein in some ballooned cells to the previously demonstrated expression of MDR-1 and MRP-1 (in vessels, astroglia, microglia, neurons, and ballooned cells) configures a brain protein pharmacoresistance map from patients with tuberous sclerosis and refractory epilepsy.}, Author = {Lazarowski, Alberto J. and Lubieniecki, Fabiana J. and Camarero, Sandra A. and Pomata, Hugo H. and Bartuluchi, Marcelo A. and Sevlever, Gustavo and Taratuto, Ana L{\'\i}a}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0887-8994}, Journal = {Pediatr Neurol}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {8508183}, Number = {1}, Organization = {Clinical Biochemistry Department, Facultad de Farmacia y Bioquimica, Universidad de Buenos Aires (UBA); Institute of Cell Biology and Neurobiology "Dr. E de Robertis", Facultad de Medicina, Universidad de Buenos Aires (UBA).}, Pages = {20-4}, Pii = {S0887-8994(05)00341-3}, Pubmed = {16376273}, Title = {New proteins configure a brain drug resistance map in tuberous sclerosis}, Uuid = {D4B7F79E-B799-4A97-B38B-46AA0E63EFDD}, Volume = {34}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.pediatrneurol.2005.06.008}} @article{Lazo:2002, Abstract = {Small molecules provide powerful tools to interrogate biological pathways but many important pathway participants remain refractory to inhibitors. For example, Cdc25 dual-specificity phosphatases regulate mammalian cell cycle progression and are implicated in oncogenesis, but potent and selective inhibitors are lacking for this enzyme class. Thus, we evaluated 10,070 compounds in a publicly available chemical repository of the National Cancer Institute for in vitro inhibitory activity against oncogenic, full-length, recombinant human Cdc25B. Twenty-one compounds had mean inhibitory concentrations of <1 microM; >75\%were quinones and >40\%were of the para-naphthoquinone structural type. Most notable was NSC 95397 (2,3-bis-[2-hydroxyethylsulfanyl]-[1,4]naphthoquinone), which displayed mixed inhibition kinetics with in vitro K(i) values for Cdc25A, -B, and -C of 32, 96, and 40 nM, respectively. NSC 95397 was more potent than any inhibitor of dual specificity phosphatases described previously and 125- to 180-fold more selective for Cdc25A than VH1-related dual-specificity phosphatase or protein tyrosine phosphatase 1b, respectively. Modification of the bis-thioethanol moiety markedly decreased enzyme inhibitory activity, indicating its importance for bioactivity. NSC 95397 showed significant growth inhibition against human and murine carcinoma cells and blocked G(2)/M phase transition. A potential Cdc25 site of interaction was postulated based on molecular modeling with these quinones. We propose that inhibitors based on this chemical structure could serve as useful tools to probe the biological function of Cdc25. 0026-895x Journal Article}, Author = {Lazo, J. S. and Nemoto, K. and Pestell, K. E. and Cooley, K. and Southwick, E. C. and Mitchell, D. A. and Furey, W. and Gussio, R. and Zaharevitz, D. W. and Joo, B. and Wipf, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Mol Pharmacol}, Keywords = {Cell Division/drug effects;Tumor Cells, Cultured;Models, Molecular;Drug Evaluation, Preclinical;EE, T abstr;Kinetics;Human;Binding Sites;Amino Acid Motifs;Cell Cycle/drug effects;cdc25 Phosphatase/*antagonists &inhibitors/chemistry;08 Aberrant cell cycle;Naphthoquinones/chemistry/*pharmacology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Enzyme Inhibitors/chemistry/*pharmacology;Cell Cycle Proteins/*antagonists &inhibitors/chemistry}, Number = {4}, Organization = {Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA. lazo\@pitt.edu}, Pages = {720-8}, Pubmed = {11901209}, Title = {Identification of a potent and selective pharmacophore for Cdc25 dual specificity phosphatase inhibitors}, Uuid = {AA39DE2B-BD53-4746-A662-90DE0547B874}, Volume = {61}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11901209}} @article{Le-Be:2006, Abstract = {The local microcircuitry of the neocortex is structurally a tabula rasa, with the axon of each pyramidal neuron having numerous submicrometer appositions with the dendrites of all neighboring pyramidal neurons, but is functionally highly selective, with synapses formed onto only a small proportion of these targets. This design leaves a vast potential for the microcircuit to rewire without extensive axonal or dendritic growth. To examine whether rewiring does take place, we used multineuron patch-clamp recordings on 12- to 14-day-old rat neocortical slices and studied long-term changes in synaptic connectivity within clusters of neurons. We found pyramidal neurons spontaneously connecting and disconnecting from each other and that exciting the slice with glutamate greatly increases the number of new connections established. Evoked emergence of new synaptic connections requires action potential activity and activation of metabotropic glutamate receptor 5, but not NMDA receptor or group II or group III metabotropic glutamate receptor activation. We also found that it is the weaker connections that are selectively eliminated. These results provide direct evidence for spontaneous and evoked rewiring of the neocortical microcircuitry involving entire functional multisynaptic connections. We speculate that this form of microcircuit plasticity enables an evolution of the microcircuit connectivity by natural selection as a function of experience.}, Author = {Le B{\'e}, Jean-Vincent V. and Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Long-Term Potentiation;Animals;Synapses;Rats;Neuronal Plasticity;Synaptic Transmission;Neocortex;Pyramidal Cells;Rats, Wistar;Animals, Newborn;Action Potentials;21 Neurophysiology;21 Circuit structure-function;Cell Nucleus;21 Activity-development;Receptors, Metabotropic Glutamate;24 Pubmed search results 2008;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {7505876}, Number = {35}, Organization = {Brain Mind Institute, Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, CH-1015 Lausanne, Switzerland.}, Pages = {13214-9}, Pii = {0604691103}, Pubmed = {16924105}, Title = {Spontaneous and evoked synaptic rewiring in the neonatal neocortex}, Uuid = {2AD01C29-29BA-47D3-AB41-92A8A4112BC4}, Volume = {103}, Year = {2006}, url = {papers/LeBé_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0604691103}} @article{Blanc:2005, Abstract = {During viral infection, fusion of the viral envelope with endosomal membranes and nucleocapsid release were thought to be concomitant events. We show here that for the vesicular stomatitis virus they occur sequentially, at two successive steps of the endocytic pathway. Fusion already occurs in transport intermediates between early and late endosomes, presumably releasing the nucleocapsid within the lumen of intra-endosomal vesicles, where it remains hidden. Transport to late endosomes is then required for the nucleocapsid to be delivered to the cytoplasm. This last step, which initiates infection, depends on the late endosomal lipid lysobisphosphatidic acid (LBPA) and its putative effector Alix/AIP1, and is regulated by phosphatidylinositol-3-phosphate (PtdIns(3)P) signalling via the PtdIns(3)P-binding protein Snx16. We conclude that the nucleocapsid is exported into the cytoplasm after the back-fusion of internal vesicles with the limiting membrane of late endosomes, and that this process is controlled by the phospholipids LBPA and PtdIns(3)P and their effectors.}, Author = {Le Blanc, and Luyet, and Pons, and Ferguson, and Emans, and Petiot, and Mayran, and Demaurex, and Faur{\'e}, and Sadoul, and Parton, and Gruenberg,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {15 Retrovirus mechanism;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {100890575}, Number = {7}, Organization = {[1] Biochemistry Department, University of Geneva, 30 quai E. Ansermet, 1211 Geneva 4, Switzerland. [2] Department of Molecular and Cell Biology, 16 Barker Hall, University of California, Berkeley, CA 94720-3202, USA. [3] These authors contributed equally to this work.}, Pages = {653-664}, Pii = {ncb1269}, Pubmed = {15951806}, Title = {Endosome-to-cytosol transport of viral nucleocapsids}, Uuid = {F4A92BC6-EA30-4CC2-B1B4-666BD3A294D2}, Volume = {7}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb1269}} @article{Le-Borgne:2003, Abstract = {In Drosophila, Notch signaling regulates binary fate decisions at each asymmetric division in sensory organ lineages. Following division of the sensory organ precursor cell (pI), Notch is activated in one daughter cell (pIIa) and inhibited in the other (pIIb). We report that the E3 ubiquitin ligase Neuralized localizes asymmetrically in the dividing pI cell and unequally segregates into the pIIb cell, like the Notch inhibitor Numb. Furthermore, Neuralized upregulates endocytosis of the Notch ligand Delta in the pIIb cell and acts in the pIIb cell to promote activation of Notch in the pIIa cell. Thus, Neuralized is a conserved regulator of Notch signaling that acts as a cell fate determinant. Polarization of the pI cell directs the unequal segregation of both Neuralized and Numb. We propose that coordinated upregulation of ligand activity by Neuralized and inhibition of receptor activity by Numb results in a robust bias in Notch signaling. 1534-5807 Journal Article}, Author = {Le Borgne, R. and Schweisguth, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Dev Cell}, Keywords = {Trans-Activation (Genetics);10 Development;Signal Transduction;Animals;Nerve Tissue Proteins/*metabolism;Models, Biological;Mutation;Cell Polarity;Trans-Activators/metabolism;Membrane Proteins/*metabolism;*Ubiquitin-Protein Ligases;Drosophila/embryology;Support, Non-U.S. Gov't;Cell Lineage;Drosophila Proteins/metabolism;Cell Division/*physiology;Endocytosis;Juvenile Hormones/metabolism;Ligases/*metabolism;Luminescent Proteins/metabolism;F}, Number = {1}, Organization = {Departement de Biologie, Ecole Normale Superieure, CNRS UMR 8542, 46, rue d'Ulm 75230, Cedex, Paris, France.}, Pages = {139-48}, Pubmed = {12852858}, Title = {Unequal segregation of Neuralized biases Notch activation during asymmetric cell division}, Uuid = {81EEC7EC-06CB-4A93-A897-1ED245ECC690}, Volume = {5}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12852858}} @article{Le-Van-Quyen:2006, Abstract = {Adult brain networks generate a wide range of oscillations. Some of these are behaviourally relevant, whereas others occur during seizures and other pathological conditions. This raises the question of how physiological oscillations differ from pathogenic ones. In this review, this issue is discussed from a developmental standpoint. Indeed, both epileptic and physiological high-frequency oscillations (HFOs) appear progressively during maturation, and it is therefore possible to determine how this program corresponds to maturation of the neuronal populations that generate these oscillations. We review here important differences in the development of neuronal populations that might contribute to their different oscillatory properties. In particular, at an early stage, the density of glutamatergic synapses is too low for physiological HFOs but an additional drive can be provided by excitatory GABA, triggering epileptic HFOs and the cascades involved in long-lasting epileptogenic transformations. This review is part of the INMED/TINS special issue Nature and nurture in brain development and neurological disorders, based on presentations at the annual INMED/TINS symposium ().}, Author = {Le Van Quyen, Michel and Khalilov, Ilgam and Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {7}, Nlm_Id = {7808616}, Number = {7}, Organization = {LENA-CNRS UPR640, Universit{\'e} Pierre et Marie Curie, H\^{o}pital de la Salp\^{e}tri\`{e}re, 47 Bd de l'H\^{o}pital, 75651 Paris Cedex 13, France.}, Pages = {419-27}, Pii = {S0166-2236(06)00112-3}, Pubmed = {16793147}, Title = {The dark side of high-frequency oscillations in the developing brain}, Uuid = {AAE2D781-03EC-4E08-9C66-8F599A57ABC9}, Volume = {29}, Year = {2006}, url = {papers/LeVanQuyen_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.06.001}} @article{Leavitt:1999, Abstract = {Neuronal migration is an essential step in normal mammalian neocortical development, and the expression of defined cellular and molecular signals within the developing cortical microenvironment is likely crucial to this process. Therapy via transplanted or manipulated endogenous precursors for diseases which involve neuronal loss may depend critically on whether newly incorporated cells can actively migrate to repopulate areas of neuronal loss within the adult brain. Previous studies demonstrated that embryonic neurons and multipotent precursors transplanted into the neocortex of adult mice undergoing targeted apoptosis of pyramidal neurons migrate long distances into neuron-deficient regions, undergo directed differentiation, accept afferent synaptic input, and make appropriate long-distance projections. The experiments presented here: (1) use time-lapse digital confocal imaging of neuronal migration in living slice cultures to assess cellular mechanisms utilized by immature neurons during such long distance migration, and (2) identify changes within the host cortical astroglial population that may contribute to this migration. Prelabeled embryonic day 17 mouse neocortical neurons were transplanted into adult mouse primary somatosensory cortex undergoing targeted apoptotic degeneration of callosal projection neurons. Four to 7 days following transplantation, living slice cultures containing the region of transplanted cells were prepared and observed. Sequential time-lapse images were recorded using a video-based digital confocal microscope. Transplanted cells displayed bipolar morphologies characteristic of migrating neuroblasts and moved in a saltatory manner with mean rates of up to 14 microm/h. To investigate whether a permissive glial phenotype may provide a potential substrate for this directed form of neuronal migration, slice cultures were immunostained with the RC2 monoclonal antibody, which identifies radial glia that act as a substrate for neuronal migration during corticogenesis. RC2 does not label mature stellate astrocytes, which express glial fibrillary acidic protein (GFAP). RC2 expression was observed in glial cells closely apposed to migrating donor neurons within the slice cultures. The timing and specificity of RC2 expression was examined immunocytochemically at various times following transplantation. RC2 immunostaining within regions of neuronal degeneration was transient, with peak staining between 3 and 7 days following transplantation. Strongly RC2-immunoreactive cells that did not express GFAP were found within these regions, but not in distant cortical regions or within control brains. RC2-positive cells were identified in recipient transgenic mice which express beta-galactosidase under a glial specific promoter. Coexpression of RC2 and beta-galactosidase identified these cells as host astroglia. These results demonstrate that adult cortical astrocytes retain the capacity to reexpress an earlier developmental phenotype that may partially underlie the observed active migration of transplanted neurons and neural precursors. Further understanding of these processes could allow directed migration of transplanted or endogenous precursors toward therapeutic cellular repopulation and complex circuit reconstruction in neocortex and other CNS regions.}, Author = {Leavitt, B. R. and Hernit-Grant, C. S. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Exp Neurol}, Keywords = {Tissue Culture;Neurons/physiology/*transplantation;Animal;02 Adult neurogenesis migration;Mice, Transgenic;Embryo/cytology;Mice, Inbred C57BL;Fetal Tissue Transplantation;Support, Non-U.S. Gov't;Cell Aging/physiology;B;Support, U.S. Gov't, Non-P.H.S.;Astrocytes/*cytology/physiology;Neocortex/*cytology/*embryology/physiology;Cell Differentiation/physiology;Support, U.S. Gov't, P.H.S.;Biological Markers;Neuroglia/*cytology;Mice;Cell Movement/physiology}, Number = {1}, Organization = {Division of Neuroscience, Harvard Medical School and, Boston, Massachusetts 02115, USA.}, Pages = {43-57.}, Title = {Mature astrocytes transform into transitional radial glia within adult mouse neocortex that supports directed migration of transplanted immature neurons}, Uuid = {F055A695-ABF9-40F5-A648-55D31ADEAE51}, Volume = {157}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10222107}} @article{Leblond:1964, Abstract = {0083-1921 Journal Article}, Author = {Leblond, C. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Natl Cancer Inst Monogr}, Keywords = {01 Adult neurogenesis general;A,F abstr}, Pages = {119-50}, Pubmed = {14147128}, Title = {Classification of Cell Populations on the Basis of Their Proliferative Behavior}, Uuid = {B14AA9DA-4190-4A76-B525-B96C796A485D}, Volume = {14}, Year = {1964}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14147128}} @article{Lechner:2004, Abstract = {Several recent studies have suggested that the adult bone marrow harbors cells that can differentiate into tissues from all three germ layers. Other reports have contradicted these findings or attributed them to cell fusion. In this study, we investigated whether bone marrow-derived cells contribute to the renewal of adult pancreatic endocrine cells, in particular insulin-producing beta-cells, in vivo. To address this issue, we studied mice transplanted with green fluorescent protein (GFP)-positive, sex-mismatched bone marrow. We also extended our studies to pancreatic injury models (partial pancreatectomy and streptozotocin administration). All animals showed stable full donor chimerism in the peripheral blood and microscopic analysis at 4-6 weeks and 3 months after transplantation, indicating that the GFP(+) and Y chromosome-positive donor bone marrow contributed substantially to blood, lymphatic, and interstitial cells in the pancreas. However, after examining >100,000 beta-cells, we found only 2 beta-cells positive for GFP, both of which were in control animals without pancreatic injury. Thus our study results did not support the concept that bone marrow contributes significantly to adult pancreatic beta-cell renewal.}, Author = {Lechner, Andreas and Yang, Yong-Guang G. and Blacken, Robyn A. and Wang, Lan and Nolan, Anna L. and Habener, Joel F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0012-1797}, Journal = {Diabetes}, Keywords = {Research Support, Non-U.S. Gov't;Cell Differentiation;Animals;Bone Marrow Transplantation;Female;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Time Factors;Male;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Pancreatectomy;Transplantation, Homologous;Islets of Langerhans;Mice;Luminescent Proteins;Genetic Markers}, Month = {3}, Nlm_Id = {0372763}, Number = {3}, Organization = {Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School and Howard Hughes Medical Institute, Boston, Massachusetts, USA.}, Pages = {616-23}, Pubmed = {14988245}, Title = {No evidence for significant transdifferentiation of bone marrow into pancreatic beta-cells in vivo}, Uuid = {87B16BCD-FB86-4459-9337-743B86942C3D}, Volume = {53}, Year = {2004}} @article{Lee:1993, Abstract = {Central nervous system disease is a frequent finding in both pediatric and adult AIDS. Microglia have been shown to be the major target of HIV-1 infection in the central nervous system. However, studies in vitro concerning susceptibility of human microglia to HIV-1 infection reported conflicting results; microglia from adult brain showed productive infection by HIV-1, whereas microglia from fetal brain did not. To investigate this further and to define the possible mechanisms responsible for this difference, we prepared highly purified human microglial cell cultures from fetuses of 16 to 24 weeks' gestation and exposed them to monocytotropic (HIV-1 JR-FL and HIV-1 JR-CSF) isolates of HIV-1. Culture supernatants were examined for the presence of p24 antigen for a 4-week period after viral exposure. Concurrently, potential cytopathic effects and cellular viral antigen expression (gp41 and p24) were examined by light microscopy in combination with immunocytochemistry. The results showed that human fetal microglia can be productively infected by HIV-1 as judged by p24 antigen capture assay, syncytia formation, and gp41 and p24 immunoreactivity of infected microglia. In addition, by electron microscopy, numerous viral particles characteristic of HIV-1 were present both in the intracellular and extracellular compartments. Uninfected cultures or astrocytes overgrown in the microglial cultures did not show evidence of infection under identical experimental conditions. These data demonstrate that human fetal microglia, like their adult counterparts, are susceptible to HIV-1 infection in vitro and can support the production of virus.}, Author = {Lee, S. C. and Hatch, W. C. and Liu, W. and Kress, Y. and Lyman, W. D. and Dickson, D. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Disease Susceptibility;HIV Core Protein p24;HIV-1;Immunohistochemistry;Human;Microscopy, Electron;Microscopy, Phase-Contrast;Fetal Diseases;Research Support, U.S. Gov't, P.H.S.;11 Glia;Microglia;Support, U.S. Gov't, P.H.S.;Acquired Immunodeficiency Syndrome;Humans}, Medline = {94027253}, Month = {10}, Nlm_Id = {0370502}, Number = {4}, Organization = {Department of Pathology (Neuropathology), Albert Einstein College of Medicine, Bronx, New York 10461.}, Pages = {1032-9}, Pubmed = {8213999}, Title = {Productive infection of human fetal microglia by HIV-1}, Uuid = {5D47D766-BB97-4626-90AC-E49E4FDF36C5}, Volume = {143}, Year = {1993}} @article{Lee:1990, Abstract = {Five beta-tubulin isotypes are expressed differentially during chicken brain development. One of these isotypes is encoded by the gene c beta 4 and has been assigned to an isotypic family designated as Class III (beta III). In the nervous system of higher vertebrates, beta III is synthesized exclusively by neurons. A beta III-specific monoclonal antibody was used to determine when during chick embryogenesis c beta 4 is expressed, the cellular localization of beta III, and the number of charge variants (isoforms) into which beta III can be resolved by isoelectric focusing. On Western blots, beta III is first detectable at stages 12-13. Thereafter, the relative abundance of beta III in brain increases steadily, apparently in conjunction with the rate of neural differentiation. The isotype was not detectable in non-neural tissue extracts from older embryos (days 10-14) and hatchlings. Western blots of protein separated by two-dimensional gel electrophoresis (2D-PAGE) reveal that the number of beta III isoforms increases from one to three during neural development. This evidence indicates that beta III is a substrate for developmentally regulated, multiple-site posttranslational modification. Immunocytochemical studies reveal that while c beta 4 expression is restricted predominantly to the nervous system, it is transiently expressed in some embryonic structures. More importantly, in the nervous system, immunoreactive cells were located primarily in the non-proliferative marginal zone of the neural epithelia. Regions containing primarily mitotic neuroblasts were virtually unstained. This localization pattern indicates that c beta 4 expression occurs either during or immediately following terminal mitosis, and suggests that beta III may have a unique role during early neuronal differentiation and neurite outgrowth.}, Author = {Lee, M. K. and Tuttle, J. B. and Rebhun, L. I. and Cleveland, D. W. and Frankfurter, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0886-1544}, Journal = {Cell Motil Cytoskeleton}, Keywords = {Organ Specificity;10 Development;Research Support, Non-U.S. Gov't;Tubulin;Immunohistochemistry;Antibodies, Monoclonal;Research Support, U.S. Gov't, P.H.S.;Chick Embryo;Antibody Specificity;Nervous System;Protein Processing, Post-Translational;Animals;Neurons}, Medline = {91077940}, Nlm_Id = {8605339}, Number = {2}, Organization = {Neuroscience Program, University of Virginia, Charlottesville.}, Pages = {118-32}, Pubmed = {2257630}, Title = {The expression and posttranslational modification of a neuron-specific beta-tubulin isotype during chick embryogenesis}, Uuid = {FBEC0C5F-D067-11DA-8A8C-000D9346EC2A}, Volume = {17}, Year = {1990}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cm.970170207}} @article{Lee:1997a, Abstract = {Several major advances in the understanding of the regulation of vertebrate neurogenesis by members of the basic helix-loop-helix (bHLH) protein family have been made in the past year. Specifically, a number of bHLH genes have been cloned and shown to convert non-neuronal fate to neuronal fate when expressed ectopically. In particular, studies on NeuroD and Neurogenin suggest a regulatory pathway, providing powerful molecular tools to study vertebrate neurogenesis.}, Author = {Lee, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Curr Opin Neurobiol}, Keywords = {F abstr;10 Development;Nervous System/*embryology;Animal;Helix-Loop-Helix Motifs/*genetics;Drosophila;Fetal Development;*Genes;Cell Differentiation/genetics}, Number = {1}, Organization = {Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Campus Box 347, Colorado 80309-0347, USA. jackie.lee\@colorado.edu}, Pages = {13-20.}, Title = {Basic helix-loop-helix genes in neural development}, Uuid = {F04FC1DC-1253-4F93-8C71-928AD3BF586A}, Volume = {7}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9039799%20http://www.biomednet.com/article/nb7112}} @article{Lee:1997b, Abstract = {NeuroD is a basic helix-loop-helix (bHLH) transcription factor cloned from a two hybrid screen designed to search for new bHLH proteins. In our previous studies, we showed that NeuroD could convert Xenopus ectoderm into fully differentiated neurons and that it could prematurely differentiate neural precursor cells in the nervous system. Recently, an insulin transcription activator, Beta-2, was cloned from a hamster insulinoma cell line by Naya et al. [Genes Dev (1995)9:1,009- 1,019]. Sequence analysis revealed that Beta-2 is the hamster homologue of NeuroD. We are currently investigating the role that NeuroD/Beta-2 plays in vertebrate neurogenesis and pancreatic development. Using Smart Source Parsing}, Author = {Lee, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Dev Neurosci}, Keywords = {F abstr;10 Development;Nervous System/*embryology;Anura/embryology;Nerve Tissue Proteins/*physiology;Animal;Fetal Development;Vertebrates/embryology;Helix-Loop-Helix Motifs/physiology}, Number = {1}, Organization = {University of Colorado Boulder, Department of Molecular, Cellular and Developmental Biology 80309-0347, USA.}, Pages = {27-32}, Title = {NeuroD and neurogenesis}, Uuid = {49BEB60F-E253-4518-B7DE-42FEFAC171C1}, Volume = {19}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9078430}} @article{Lee:2000b, Abstract = {The mechanisms that regulate patterning and growth of the developing cerebral cortex remain unclear. Suggesting a role for Wnt signaling in these processes, multiple Wnt genes are expressed in selective patterns in the embryonic cortex. We have examined the role of Wnt-3a signaling at the caudomedial margin of the developing cerebral cortex, the site of hippocampal development. We show that Wnt-3a acts locally to regulate the expansion of the caudomedial cortex, from which the hippocampus develops. In mice lacking Wnt-3a, caudomedial cortical progenitor cells appear to be specified normally, but then underproliferate. By mid-gestation, the hippocampus is missing or represented by tiny populations of residual hippocampal cells. Thus, Wnt-3a signaling is crucial for the normal growth of the hippocampus. We suggest that the coordination of growth with patterning may be a general role for Wnts during vertebrate development.}, Author = {Lee, S. M. and Tole, S. and Grove, E. and McMahon, A. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {10 Development;Signal Transduction;Animals;10 Hippocampus;Gene Expression Regulation, Developmental;Proteins;Telencephalon;Hippocampus;Mammals;Embryonic and Fetal Development;Wnt Proteins;Research Support, U.S. Gov't, P.H.S.;Mice, Knockout;Cerebral Cortex;Neurons;Mice;Stem Cells;Gestational Age}, Medline = {20098485}, Month = {2}, Nlm_Id = {8701744}, Number = {3}, Organization = {Department of Molecular Biology, The Biolabs, Harvard University, Cambridge, MA 02138, USA.}, Pages = {457-67}, Pubmed = {10631167}, Title = {A local Wnt-3a signal is required for development of the mammalian hippocampus}, Uuid = {E0841A51-7113-11DA-9A4D-000D9346EC2A}, Volume = {127}, Year = {2000}, url = {papers/Lee_Development2000.pdf}} @article{Lee:2002b, Abstract = {Bis (also called Bag-3), identified as a novel Bcl-2-interacting protein, has been shown to enhance anti-cell death activity of Bcl-2. Because ischemia/reperfusion induces expression of Bcl-2, we examined the changes in the pattern of Bis expression in the adult rat hippocampus after transient forebrain ischemia. Western blot analysis with protein extracts from the hippocampus showed that, compared with controls, levels of Bis were markedly increased seven days after ischemia. An immunohistochemical study showed that the expression of Bis increased preferentially in the CA1 and the dentate hilar regions, and peaked at 3-7 days after reperfusion. The temporal and spatial patterns of expression for both Bis and glial fibrillary acidic protein (GFAP) were very similar, and double immunofluorescence histochemistry showed that Bis was expressed in reactive astrocytes, which express GFAP. Immunolabeling of adjacent sections with anti-Bcl-2 and anti-Hsp70 antibodies revealed that the pattern of Bis expression closely correlates with that of Bcl-2, but clearly differs from that of Hsp70. Coexpression of Bis and Bcl-2 in reactive astrocytes was confirmed by double immunofluorescence histochemistry. Our results demonstrate that reactive astrocytes transiently up-regulate Bis after ischemia/reperfusion in the adult rat hippocampus. However, the precise role of Bis in the astrocytic response to ischemia/reperfusion in relation to Bcl-2 remains to be determined. 0014-4886 Journal Article}, Author = {Lee, M. Y. and Kim, S. Y. and Shin, S. L. and Choi, Y. S. and Lee, J. H. and Tsujimoto, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Exp Neurol}, Keywords = {Carrier Proteins/analysis/immunology/*metabolism;Heat-Shock Proteins 70/analysis/immunology;Hippocampus/cytology;Rats, Sprague-Dawley;Ischemic Attack, Transient/*metabolism;Rats;06 Adult neurogenesis injury induced;Up-Regulation/physiology;Proto-Oncogene Proteins c-bcl-2/analysis/immunology/*metabolism;D pdf;Animals;Astrocytes/chemistry/*metabolism;Antibodies;Support, Non-U.S. Gov't;Male}, Number = {2}, Organization = {Department of Anatomy, The Catholic University of Korea, Seoul 137-701, Korea.}, Pages = {338-46}, Pubmed = {12061864}, Title = {Reactive astrocytes express bis, a bcl-2-binding protein, after transient forebrain ischemia}, Uuid = {33C96DBD-8508-47A7-9007-EF34656794EE}, Volume = {175}, Year = {2002}, url = {papers/Lee_ExpNeurol2002}} @article{Lee:2001, Abstract = {Human bone marrow-derived mesenchymal stem cells (hMSCs) are being investigated for a potential therapeutic role as hematopoietic support cells following chemo-radiotherapy and as vehicles of gene delivery. Although hMSCs can be safely infused into humans and experimental animals, there is limited evidence regarding their engraftment and proliferation in vivo. We developed a drug resistance gene transfer strategy to mark and selectively enrich marked hMSCs using chemotherapy. We have determined that hMSCs are markedly sensitized to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in vitro when pretreated with O(6)-benzylguanine (BG) resulting in a more than four-fold decrease in BCNU IC(90). The MFG retroviral vector encoding a bicistronic transcript for green fluorescent protein (GFP) and mutant (G156A)-methylguanine methyltransferase (G156A-MGMT), which encodes O(6)-alkylguanine-DNA alkyltransferase (AGT), conferring, BG plus BCNU resistance, transduced a high percentage of hMSCs. Transduced hMSCs had high expression of GFP and AGT and became significantly resistant to BG and BCNU. Furthermore, the proportion of GFP expressing transduced hMSCs increased from 32 +/- 14\%to 70 +/- 14\%following BG and BCNU treatment in vitro. Intravenously infused hMSCs were detected in NOD-SCID mice 8 weeks later by PCR analysis but could not be recultured from the bone marrow. GFP-expressing hMSCs inoculated into subcutaneous wounds in nonobese diabetic-severe combined immunodeficient (NOD-SCID) mouse could be recultured at a low frequency, but enriched by BG and BCNU treatment from 0.05 +/- 0.03\%to 0.55 +/- 0.4 (p = 0.028, Welch t-test). Our results indicate that hMSCs are sensitive to BG and BCNU, predicting significant toxicity to the hematopoietic microenvironment with this therapy. G156A-MGMT is a powerful selectable gene for a second marker gene in hMSCs. Drug resistance gene transfer into hMSCs may allow in vivo enrichment of hMSCs when MSC homing and engraftment into target tissues is optimized.}, Author = {Lee, K. and Gerson, S. L. and Maitra, B. and Ko\c{c}, O. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1525-8165}, Journal = {J Hematother Stem Cell Res}, Keywords = {Guanine;Mice, SCID;Infusions, Intravenous;Cell Survival;Genetic Vectors;O(6)-Methylguanine-DNA Methyltransferase;Green Fluorescent Proteins;Luminescent Proteins;Dystrophin;Brain;Cells, Cultured;Animals;Flow Cytometry;Mesoderm;Research Support, U.S. Gov't, P.H.S.;DNA;Liver;Tissue Distribution;Transfection;Cell Transplantation;Spleen;11 Glia;Mice, Inbred NOD;Retroviridae;Bone Marrow Cells;Dose-Response Relationship, Drug;Antineoplastic Agents;Mutation, Missense;Recombinant Fusion Proteins;Mice;Stem Cells;Lung;Humans;Carmustine;Drug Resistance, Multiple}, Medline = {21528902}, Month = {10}, Nlm_Id = {100892915}, Number = {5}, Organization = {Department of Medicine, Case Western Reserve University, Ireland Cancer Center of University Hospitals of Cleveland, OH 44106, USA.}, Pages = {691-701}, Pubmed = {11672516}, Title = {G156A MGMT-transduced human mesenchymal stem cells can be selectively enriched by O6-benzylguanine and BCNU}, Uuid = {1EAE6B74-95AB-48CB-81C8-C18C507AC8B0}, Volume = {10}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/152581601753193913}} @article{Lee:2007, Abstract = {Activated microglia are thought to undergo apoptosis as a self-regulatory mechanism. To better understand molecular mechanisms of the microglial apoptosis, apoptosis-resistant variants of microglial cells were selected and characterized. The expression of lipocalin 2 (lcn2) was significantly down-regulated in the microglial cells that were resistant to NO-induced apoptosis. lcn2 expression was increased by inflammatory stimuli in microglia. The stable expression of lcn2 as well as the addition of rLCN2 protein augmented the sensitivity of microglia to the NO-induced apoptosis, while knockdown of lcn2 expression using short hairpin RNA attenuated the cell death. Microglial cells with increased lcn2 expression were more sensitive to other cytotoxic agents as well. Thus, inflammatory activation of microglia may lead to up-regulation of lcn2 expression, which sensitizes microglia to the self-regulatory apoptosis. Additionally, the stable expression of lcn2 in BV-2 microglia cells induced a morphological change of the cells into the round shape with a loss of processes. Treatment of primary microglia cultures with the rLCN2 protein also induced the deramification of microglia. The deramification of microglia was closely related with the apoptosis-prone phenotype, because other deramification-inducing agents such as cAMP-elevating agent forskolin, ATP, and calcium ionophore also rendered microglia more sensitive to cell death. Taken together, our results suggest that activated microglia may secrete LCN2 protein, which act in an autocrine manner to sensitize microglia to the self-regulatory apoptosis and to endow microglia with an amoeboid form, a canonical morphology of activated microglia in vivo.}, Author = {Lee, Shinrye and Lee, Jayoung and Kim, Sangseop and Park, Jae-Yong Y. and Lee, Won-Ha H. and Mori, Kiyoshi and Kim, Sang-Hyun H. and Kim, In Kyeom and Suk, Kyoungho}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {research support, non-u.s. gov't;11 Glia;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {2985117R}, Number = {5}, Organization = {Department of Pharmacology, Kyungpook National University School of Medicine, 101 Dong-in, Joong-gu, Daegu 700-422, Korea.}, Pages = {3231-41}, Pii = {179/5/3231}, Pubmed = {17709539}, Title = {A dual role of lipocalin 2 in the apoptosis and deramification of activated microglia}, Uuid = {5CB0A68B-EA0E-4FA4-A92A-5E27D5AF0DD9}, Volume = {179}, Year = {2007}} @article{Lee:2002a, Abstract = {The adult brain contains small populations of neural precursor cells (NPC) that can give rise to new neurons and glia, and may play important roles in learning and memory, and recovery from injury. Growth factors can influence the proliferation, differentiation and survival of NPC, and may mediate responses of NPC to injury and environmental stimuli such as enriched environments and physical activity. We now report that neurotrophin expression and neurogenesis can be modified by a change in diet. When adult mice are maintained on a dietary restriction (DR) feeding regimen, numbers of newly generated cells in the dentate gyrus of the hippocampus are increased, apparently as the result of increased cell survival. The new cells exhibit phenotypes of neurons and astrocytes. Levels of expression of brain- derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are increased by DR, while levels of expression of high-affinity receptors for these neurotrophins (trkB and trkC) are unchanged. In addition, DR increases the ratio of full-length trkB to truncated trkB in the hippocampus. The ability of a change in diet to stimulate neurotrophin expression and enhance neurogenesis has important implications for dietary modification of neuroplasticity and responses of the brain to injury and disease.}, Author = {Lee, J. and Seroogy, K. B. and Mattson, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurochem}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {3}, Organization = {Laboratory of Neurosciences, National Institute on Aging Gerontology Research Center Baltimore, Maryland 21224, USA.}, Pages = {539-47.}, Title = {Dietary restriction enhances neurotrophin expression and neurogenesis in the hippocampus of adult mice}, Uuid = {EC1ED654-A87C-413B-820C-7C833D23C933}, Volume = {80}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11905999}} @article{Lee:1997, Abstract = {Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a "rim-to-core" neurogenetic pattern rather than the characteristic "inside-out" pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the tish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures. The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.}, Author = {Lee, K. S. and Schottler, F. and Collins, J. L. and Lanzino, G. and Couture, D. and Rao, A. and Hiramatsu, K. and Goto, Y. and Hong, S. C. and Caner, H. and Yamamoto, H. and Chen, Z. F. and Bertram, E. and Berr, S. and Omary, R. and Scrable, H. and Jackson, T. and Goble, J. and Eisenman, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Magnetic Resonance Imaging;Animals;Image Processing, Computer-Assisted;Rats;Neural Pathways;21 Epilepsy;Female;Epilepsy;21 Dysplasia-heterotopia;Disease Models, Animal;Male;Prosencephalon;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;24 Pubmed search results 2008;Choristoma;Electroencephalography;Rats, Mutant Strains}, Medline = {97383273}, Month = {8}, Nlm_Id = {8102140}, Number = {16}, Organization = {Department of Neurological Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.}, Pages = {6236-42}, Pubmed = {9236234}, Title = {A genetic animal model of human neocortical heterotopia associated with seizures}, Uuid = {039640AD-2F43-4AC6-AA37-C5C00FEA17A1}, Volume = {17}, Year = {1997}, url = {papers/Lee_JNeurosci1997.pdf}} @article{Lee:2006, Abstract = {After brain injury, neuroblast cells from the subventricular zone (SVZ) expand and migrate toward damaged tissue. The mechanisms that mediate these neurogenic and migratory responses remain to be fully dissected. Here, we show that bromodeoxyuridine-labeled and doublecortin-positive cells from the SVZ colocalize with the extracellular protease matrix metalloproteinase-9 (MMP-9) during the 2 week recovery period after transient focal cerebral ischemia in mice. Treatment with the broad spectrum MMP inhibitor GM6001 significantly decreases the migration of doublecortin-positive cells that extend from the SVZ into the striatum. These data suggest that MMPs are involved in endogenous mechanisms of neurogenic migration as the brain seeks to heal itself after injury.}, Author = {Lee, Seong-Ryong R. and Kim, Hahn-Young Y. and Rogowska, Jadwiga and Zhao, Bing-Qiao Q. and Bhide, Pradeep and Parent, Jack M. and Lo, Eng H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8102140}, Number = {13}, Organization = {Department of Neurology and Radiology, Massachusetts General Hospital, Boston, Massachusetts 02129, USA.}, Pages = {3491-5}, Pii = {26/13/3491}, Pubmed = {16571756}, Title = {Involvement of matrix metalloproteinase in neuroblast cell migration from the subventricular zone after stroke}, Uuid = {596A2651-E881-4E98-8357-36465C0FA116}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4085-05.2006}} @article{Lee:2000a, Abstract = {Endogenous calcium binding ratios (kappaS) in dendrites of cultured hippocampal neurons were estimated according to the single compartment model for transients in intracellular Ca2+ concentration ([Ca2+]). In addition, the electrophysiological characteristics of neurons were classified by their autaptic currents and intrinsic firing patterns. These data were analysed in order to determine whether a correlation between Ca2+ buffers and electrophysiological type exists. Ca2+ binding ratios of endogenous buffers were estimated by eliciting [Ca2+] transients with short depolarizations, while cells were loaded with fura-2. Two types of estimates could be obtained: one termed kappaS(tau), based on analysing time constants (tau) of [Ca2+] transients, and another termed kappaS(dCa), derived from an analysis of initial amplitudes of [Ca2+] transients. Values for kappaS(tau) and kappaS(dCa) were estimated as 57 +/- 10 (mean +/- s.d., n = 10) and 60 +/- 14 (n = 10), respectively, in excitatory neurons, and 130 +/- 50 (n = 11) and 150 +/- 70 (n = 11), respectively, in inhibitory neurons. The kappaS values of excitatory and inhibitory cells were significantly different from each other, regardless of the measurement method (Student's t test, P < 0.01). However, there was no significant difference in kappaS between the groups classified according to firing patterns. Although kappaS(tau) values were well matched to those of kappaS(dCa) in most excitatory cells, the two values did not agree in three out of the fourteen inhibitory cells investigated. In these cells, the first few [Ca2+] transients after obtaining the whole cell configuration displayed a double exponential decay, suggesting that buffers with slow binding kinetics, such as parvalbumin, are involved. This hypothesis is further explored in an accompanying paper.}, Author = {Lee, S. H. and Rosenmund, C. and Schwaller, B. and Neher, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Neurons;Dendrites;Cell Compartmentation;21 Neurophysiology;Kinetics;Hippocampus;research support, non-u.s. gov't ;Immunohistochemistry;Models, Neurological;21 Calcium imaging;Calcium;Rats;Animals;comparative study ;24 Pubmed search results 2008;Buffers;Cells, Cultured}, Month = {6}, Nlm_Id = {0266262}, Organization = {Max Planck Institute for Biophysical Chemistry, Department of Membrane Biophysics, D-37077 Gottingen, Germany.}, Pages = {405-18}, Pii = {PHY_9975}, Pubmed = {10835043}, Title = {Differences in Ca2+ buffering properties between excitatory and inhibitory hippocampal neurons from the rat}, Uuid = {32C55380-96F5-411F-827E-DAD995F2BC7C}, Volume = {525 Pt 2}, Year = {2000}, url = {papers/Lee_JPhysiol2000.pdf}} @article{Lee:2000, Abstract = {Ageing of the brain leads to impairments in cognitive and motor skills, and is the major risk factor for several common neurological disorders such as Alzheimer disease (AD) and Parkinson disease (PD). Recent studies suggest that normal brain ageing is associated with subtle morphological and functional alterations in specific neuronal circuits, as opposed to large-scale neuronal loss. In fact, ageing of the central nervous system in diverse mammalian species shares many features, such as atrophy of pyramidal neurons, synaptic atrophy, decrease of striatal dopamine receptors, accumulation of fluorescent pigments, cytoskeletal abnormalities, and reactive astrocytes and microglia. To provide the first global analysis of brain ageing at the molecular level, we used oligonucleotide arrays representing 6,347 genes to determine the gene-expression profile of the ageing neocortex and cerebellum in mice. Ageing resulted in a gene-expression profile indicative of an inflammatory response, oxidative stress and reduced neurotrophic support in both brain regions. At the transcriptional level, brain ageing in mice displays parallels with human neurodegenerative disorders. Caloric restriction, which retards the ageing process in mammals, selectively attenuated the age-associated induction of genes encoding inflammatory and stress responses.}, Author = {Lee, C. K. and Weindruch, R. and Prolla, T. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Aging;24 Pubmed search results 2008;21 Neurodegenerative;Research Support, Non-U.S. Gov't;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred C57BL;Neocortex;Cerebellum;RNA Stability;Gene Expression;Mice;Animals;Male;RNA, Messenger;Brain}, Medline = {20347713}, Month = {7}, Nlm_Id = {9216904}, Number = {3}, Organization = {Environmental Toxicology Center, University of Wisconsin, Madison, Wisconsin, USA.}, Pages = {294-7}, Pubmed = {10888876}, Title = {Gene-expression profile of the ageing brain in mice}, Uuid = {DEE8F3DD-0D16-4970-BD14-1AF4A73E32FA}, Volume = {25}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/77046}} @article{Lee:2002, Abstract = {Rats repeatedly ran through a sequence of spatial receptive fields of hippocampal CA1 place cells in a fixed temporal order. A novel combinatorial decoding method reveals that these neurons repeatedly fired in precisely this order in long sequences involving four or more cells during slow wave sleep (SWS) immediately following, but not preceding, the experience. The SWS sequences occurred intermittently in brief ( approximately 100 ms) bursts, each compressing the behavioral sequence in time by approximately 20-fold. This rapid encoding of sequential experience is consistent with evidence that the hippocampus is crucial for spatial learning in rodents and the formation of long-term memories of events in time in humans.}, Author = {Lee, Albert K. and Wilson, Matthew A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-07-31 19:36:37 +0000}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Signal Transduction;Rats, Long-Evans;Animals;Signal Processing, Computer-Assisted;Rats;Neural Pathways;Memory;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Hippocampus;Pyramidal Cells;Male;Sleep;research support, non-u.s. gov't ;Action Potentials;Learning;21 Neurophysiology;Neuropsychological Tests; spontaneous activity; hippocampus; Technique; Methods; Computational Biology;}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Picower Center for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. albert\@cortical.mit.edu}, Pages = {1183-94}, Pii = {S0896627302010966}, Pubmed = {12495631}, Title = {Memory of sequential experience in the hippocampus during slow wave sleep}, Uuid = {93CDA466-9C3E-491D-891D-5BBEE281CA23}, Volume = {36}, Year = {2002}, url = {papers/Lee_Neuron2002.pdf}} @article{Lee:2006a, Abstract = {Despite decades of evidence for functional plasticity in the adult brain, the role of structural plasticity in its manifestation remains unclear. To examine the extent of neuronal remodeling that occurs in the brain on a day-to-day basis, we used a multiphoton-based microscopy system for chronic in vivo imaging and reconstruction of entire neurons in the superficial layers of the rodent cerebral cortex. Here we show the first unambiguous evidence (to our knowledge) of dendrite growth and remodeling in adult neurons. Over a period of months, neurons could be seen extending and retracting existing branches, and in rare cases adding new branch tips. Neurons exhibiting dynamic arbor rearrangements were GABA-positive non-pyramidal interneurons, while pyramidal cells remained stable. These results are consistent with the idea that dendritic structural remodeling is a substrate for adult plasticity and they suggest that circuit rearrangement in the adult cortex is restricted by cell type-specific rules.}, Author = {Lee, Wei-Chung Allen C. and Huang, Hayden and Feng, Guoping and Sanes, Joshua R. and Brown, Emery N. and So, Peter T. and Nedivi, Elly}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {101183755}, Number = {2}, Organization = {The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.}, Pages = {e29}, Pii = {05-PLBI-RA-0998R3}, Pubmed = {16366735}, Title = {Dynamic remodeling of dendritic arbors in GABAergic interneurons of adult visual cortex}, Uuid = {25E80549-A835-486F-8CBE-FFD75F4339C8}, Volume = {4}, Year = {2006}, url = {papers/Lee_PLoSBiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0040029}} @article{Lehmann:2005, Abstract = {The proliferation and survival of new cells in the dentate gyrus of mammals is a complex process that is subject to numerous influences, presenting a confusing picture. We suggest regarding these processes on the level of small networks, which can be simulated in silico and which illustrate in a nutshell the influences that proliferating cells exert on plasticity and the conditions they require for survival. Beyond the insights gained by this consideration, we review the available literature on factors that regulate cell proliferation and neurogenesis in the dentate gyrus in vivo. It turns out that the rate of cell proliferation and excitatory afferents via the perforant path interactively determine cell survival, such that the best network stability is achieved when either of the two is increased whereas concurrent activation of the two factors lowers cell survival rates. Consequently, the mitotic activity is regulated by systemic parameters in compliance with the hippocampal network's requirements. The resulting neurogenesis, in contrast, depends on local factors, i.e. the activity flow within the network. In the process of cell differentiation and survival, each cell's spectrum of afferent and efferent connections decides whether it will integrate into the network or undergo apoptosis, and it is the current neuronal activity which determines the synaptic spectrum. We believe that this framework will help explain the biology of dentate cell proliferation and provide a basis for future research hypotheses.}, Author = {Lehmann, Konrad and Butz, Markus and Teuchert-Noodt, Gertraud}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {8918110}, Number = {12}, Organization = {Department Neuroanatomy, Fac. Biology, University of Bielefeld, PO Box 100131, 33501 Bielefeld, Germany. Konrad.Lehmann\@uni-bielefeld.de}, Pages = {3205-16}, Pii = {EJN4156}, Pubmed = {16026459}, Title = {Offer and demand: proliferation and survival of neurons in the dentate gyrus}, Uuid = {2491E0E2-EC2B-48D8-9117-6D550B81E16C}, Volume = {21}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2005.04156.x}} @article{Lehnardt:2003, Abstract = {Innate immunity is an evolutionarily ancient system that provides organisms with immediately available defense mechanisms through recognition of pathogen-associated molecular patterns. We show that in the CNS, specific activation of innate immunity through a Toll-like receptor 4 (TLR4)-dependent pathway leads to neurodegeneration. We identify microglia as the major lipopolysaccharide (LPS)-responsive cell in the CNS. TLR4 activation leads to extensive neuronal death in vitro that depends on the presence of microglia. LPS leads to dramatic neuronal loss in cultures prepared from wild-type mice but does not induce neuronal injury in CNS cultures derived from tlr4 mutant mice. In an in vivo model of neurodegeneration, stimulating the innate immune response with LPS converts a subthreshold hypoxic-ischemic insult from no discernable neuronal injury to severe axonal and neuronal loss. In contrast, animals bearing a loss-of-function mutation in the tlr4 gene are resistant to neuronal injury in the same model. The present study demonstrates a mechanistic link among innate immunity, TLRs, and neurodegeneration.}, Author = {Lehnardt, Seija and Massillon, Leon and Follett, Pamela and Jensen, Frances E. and Ratan, Rajiv and Rosenberg, Paul A. and Volpe, Joseph J. and Vartanian, Timothy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Mice, Inbred BALB C;Nerve Degeneration;Bystander Effect;Animals;Coculture Techniques;Rats;Ganglia, Spinal;Apoptosis;Microglia;Mice, Inbred C3H;Rats, Sprague-Dawley;Lipopolysaccharides;Hypoxia-Ischemia, Brain;11 Glia;Antigens, CD14;14 Immune;Spinal Cord;Research Support, U.S. Gov't, P.H.S.;Chick Embryo;Cerebral Cortex;Neurons;Mice;24 Pubmed search results 2008;Immunity, Natural;Research Support, Non-U.S. Gov't}, Medline = {22735862}, Month = {7}, Nlm_Id = {7505876}, Number = {14}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {8514-9}, Pii = {1432609100}, Pubmed = {12824464}, Title = {Activation of innate immunity in the CNS triggers neurodegeneration through a Toll-like receptor 4-dependent pathway}, Uuid = {1F636BBD-71DF-4BAC-9CD5-301D41E442FF}, Volume = {100}, Year = {2003}, url = {papers/Lehnardt_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1432609100}} @misc{Leibler:1994, Author = {Leibler, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0028-0836}, Keywords = {20 Networks;Adenosine Triphosphate;DNA;Electrodes;Biophysics;comment;Motion;Colloids;24 Pubmed search results 2008;news}, Month = {8}, Nlm_Id = {0410462}, Number = {6489}, Pages = {412-3}, Pubmed = {8047156}, Title = {Nature}, Uuid = {B65FE09C-D988-43E9-BDD2-D847B07B99D7}, Volume = {370}, Year = {1994}, url = {papers/Leibler_1994.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/370412a0}} @article{Leichnetz:2001, Abstract = {The afferent and efferent cortical and subcortical connections of the medial posterior parietal cortex (area 7m) were studied in cebus (Cebus apella) and macaque (Macaca fascicularis) monkeys using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique. The principal intraparietal corticocortical connections of area 7m in both cebus and macaque cases were with the ipsilateral medial bank of the intraparietal sulcus (MIP) and adjacent superior parietal lobule (area 5), inferior parietal lobule (area 7a), lateral bank of the IPS (area 7ip), caudal parietal operculum (PGop), dorsal bank of the caudal superior temporal sulcus (visual area MST), and medial prestriate cortex (including visual area PO and caudal medial lobule). Its principal frontal corticocortical connections were with the prefrontal cortex in the shoulder above the principal sulcus and the cortex in the shoulder above the superior ramus of the arcuate sulcus (SAS), the area purported to contain the smooth eye movement-related frontal eye field (FEFsem) in the cebus monkey by other investigators. There were moderate connections with the cortex in the rostral bank of the arcuate sulcus (purported to contain the saccade-related frontal eye field; FEFsac), supplementary eye field (SEF), and rostral dorsal premotor area (PMDr). Area 7m also had major connections with the cingulate cortex (area 23), particularly the ventral bank of the cingulate sulcus. The principal subcortical connections of area 7m were with the dorsal portion of the ventrolateral thalamic (VLc) nucleus, lateral posterior thalamic nucleus, lateral pulvinar, caudal mediodorsal thalamic nucleus and medial pulvinar, central lateral, central superior lateral, and central inferior intralaminar thalamic nuclei, dorsolateral caudate nucleus and putamen, middle region of the claustrum, nucleus of the diagonal band, zona incerta, pregeniculate nucleus, anterior and posterior pretectal nuclei, intermediate layer of the superior colliculus, nucleus of Darkschewitsch and dorsomedial parvicellular red nucleus (macaque cases only), dorsal, dorsolateral and lateral basilar pontine nuclei, nucleus reticularis tegmenti pontis, locus ceruleus, and superior central nucleus. The findings are discussed in terms of the possibility that area 7m contains a "medial parietal eye field" and belongs to a neural network of oculomotor-related structures that plays a role in the control of eye movement.}, Author = {Leichnetz, G. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0003-276X}, Journal = {Anat Rec}, Keywords = {Species Specificity;Comparative Study;Macaca fascicularis;Neural Pathways;Eye Movements;Parietal Lobe;Cebus;Horseradish Peroxidase;Animals;24 Pubmed search results 2008;Frontal Lobe}, Medline = {21259445}, Month = {6}, Nlm_Id = {0370540}, Number = {2}, Organization = {Department of Anatomy, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298-0709, USA. gleichne\@hsc.vcu.edu}, Pages = {215-36}, Pii = {10.1002/ar.1082}, Pubmed = {11360237}, Title = {Connections of the medial posterior parietal cortex (area 7m) in the monkey}, Uuid = {8B7937EC-6C97-453F-B727-F3866482FD91}, Volume = {263}, Year = {2001}} @article{Leimig:2002, Abstract = {Protective protein/cathepsin A (PPCA), a lysosomal carboxypeptidase, is deficient in the neurodegenerative lysosomal disorder galactosialidosis (GS). PPCA(-/-) mice display a disease course similar to that of severe human GS, resulting in nephropathy, ataxia, and premature death. Bone marrow transplantation (BMT) in mutant animals using transgenic BM overexpressing the corrective enzyme in either erythroid cells or monocytes/macrophages has proven effective for the improvement of the phenotype, and encouraged the use of genetically modified BM cells for ex vivo gene therapy of GS. Here, we established stable donor hematopoiesis in PPCA(-/-) mice that received hematopoietic progenitors transduced with a murine stem cell virus (MSCV)-based, bicistronic retroviral vector overexpressing PPCA and the green fluorescent protein (GFP) marker. We observed complete correction of the disease phenotype in the systemic organs up to 10 months after transplantation. PPCA(+) BM-derived cells were detected in all tissues, with the highest expression in liver, spleen, BM, thymus, and lung. In addition, a lysosomal immunostaining was seen in nonhematopoietic cells, indicating efficient uptake of the corrective protein by these cells and cross-correction. Expression in the brain occurred throughout the parenchyma but was mainly localized on perivascular areas. However, PPCA expression in the central nervous system was apparently sufficient to delay the onset of Purkinje cell degeneration and to correct the ataxia. The long-term expression and internalization of the PPCA by cells of systemic organs and the clear improvement of the neurologic phenotype support the use of this approach for the treatment of GS in humans. (Blood. 2002;99:3169-3178)}, Author = {Leimig, Thasia and Mann, Linda and Martin, Maria del Pilar e. l. . P. and Bonten, Erik and Persons, Derek and Knowles, James and Allay, James A. and Cunningham, John and Nienhuis, Arthur W. and Smeyne, Richard and d'Azzo, Alessandra}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Neuraminidase;Ataxia;Tissue Distribution;beta-Galactosidase;Animals;Carboxypeptidase C;Treatment Outcome;Lysosomal Storage Diseases;Central Nervous System Diseases;Mucolipidoses;11 Glia;Green Fluorescent Proteins;Hematopoietic Stem Cell Transplantation;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Gene Therapy;Mice, Knockout;Organ Specificity;Carboxypeptidases;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Kidney Diseases;Research Support, Non-U.S. Gov't}, Medline = {21961532}, Month = {5}, Nlm_Id = {7603509}, Number = {9}, Organization = {St Jude Children's Research Hospital, Memphis, TN 38105, USA.}, Pages = {3169-78}, Pubmed = {11964280}, Title = {Functional amelioration of murine galactosialidosis by genetically modified bone marrow hematopoietic progenitor cells}, Uuid = {157BF097-6CC7-4EB4-82DE-E904BE775A25}, Volume = {99}, Year = {2002}} @article{Leinekugel:2002, Abstract = {The behavior of immature cortical networks in vivo remains largely unknown. Using multisite extracellular and patch-clamp recordings, we observed recurrent bursts of synchronized neuronal activity lasting 0.5 to 3 seconds that occurred spontaneously in the hippocampus of freely moving and anesthetized rat pups. The influence of slow rhythms (0.33 and 0.1 hertz) and the contribution of both gamma-aminobutyric acid A-mediated and glutamate receptor-mediated synaptic signals in the generation of hippocampal bursts was reminiscent of giant depolarizing potentials observed in vitro. This earliest pattern, which diversifies during the second postnatal week, could provide correlated activity for immature neurons and may underlie activity-dependent maturation of the hippocampal network.}, Author = {Leinekugel, Xavier and Khazipov, Rustem and Cannon, Robert and Hirase, Hajime and Ben-Ari, Yehezkel and Buzs{\'a}ki, Gy{\"o}rgy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 03:04:18 +0000}, Issn = {1095-9203}, Journal = {Science}, Keywords = {gamma-Aminobutyric Acid;Receptors, Glutamate;Animals;Synapses;Evoked Potentials;Rats;Research Support, U.S. Gov't, Non-P.H.S.;Synaptic Transmission;Patch-Clamp Techniques;21 Epilepsy;Hippocampus;Pyramidal Cells;Rats, Wistar;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Receptors, GABA-A;Neurons;21 Neurophysiology;21 Cortical oscillations;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't; currOpinRvw}, Medline = {22061478}, Month = {6}, Nlm_Id = {0404511}, Number = {5575}, Organization = {INMED, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM) U29, Avenue de Luminy, Boite Postale 13, 13273 Marseille Cedex 09, France.}, Pages = {2049-52}, Pii = {296/5575/2049}, Pubmed = {12065842}, Title = {Correlated bursts of activity in the neonatal hippocampus in vivo}, Uuid = {56665EEB-078B-4456-B55A-6D0FC3ED4D53}, Volume = {296}, Year = {2002}, url = {papers/Leinekugel_Science2002.pdf}, Bdsk-File-2 = {papers/Leinekugel_Science2002a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1071111}} @article{Lemasson:2005, Abstract = {In mammals, the olfactory bulb (OB) constitutes one of two regions of the postnatal brain with continuous neurogenesis throughout life. Despite intense explorations of neuronal replacement in the adult OB, little is known about the mechanisms that operate at earlier postnatal stages. This question is particularly pertinent, because the majority of local interneurons are born in the neonate, when olfaction controls vital functions. Here, we analyzed the recruitment of newborn cells to the granule cell (GC) layer (GCL) and found that the postnatal mouse OB is supplied with two spatiotemporally distinct populations of newborn interneurons. Early born [postnatal day 3 (P3) to P7] GCs constitute a threefold larger population compared with those generated later (P14-P60), and some of them are produced locally within the OB itself. Newborn interneurons generated at P3-P7 were predominantly targeted to the external edge of the GCL, whereas newly generated cells were positioned deeper in older mice. Additionally, although approximately 50\%of adult newborn cells were eliminated within a few weeks of reaching the OB, almost the entire population of early born GCs survived until adulthood. Importantly, early olfactory experience specifically modifies the number of newborn GCs in neonates but leaves unaltered the amount of neurons generated during adulthood. Together, these results demonstrate that early postnatal neurogenesis endows the neonate bulbar circuit with newborn GCs that differ morphologically and functionally from those produced in the adult.}, Author = {Lemasson, Morgane and Saghatelyan, Armen and Olivo-Marin, Jean-Christophe C. and Lledo, Pierre-Marie M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;02 Adult neurogenesis migration;13 Olfactory bulb anatomy}, Month = {7}, Nlm_Id = {8102140}, Number = {29}, Organization = {Laboratory of Perception and Memory, Centre National de la Recherche Scientifique, Unit{\'e} de Recherche Associ{\'e}e 2182, Pasteur Institute, 75724 Paris Cedex 15, France.}, Pages = {6816-25}, Pii = {25/29/6816}, Pubmed = {16033891}, Title = {Neonatal and adult neurogenesis provide two distinct populations of newborn neurons to the mouse olfactory bulb}, Uuid = {06ECAA00-B357-4FA4-9E7B-8083D364E5BB}, Volume = {25}, Year = {2005}, url = {papers/Lemasson_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1114-05.2005}} @article{Lemkine:2005, Abstract = {Thyroid hormones (TH) are essential for brain development. However, information on if and how this key endocrine factor affects adult neurogenesis is fragmentary. We thus investigated the effects of TH on proliferation and apoptosis of stem cells in the subventricular zone (SVZ), as well as on migration of transgene-tagged neuroblasts out of the stem cell niche. Hypothyroidism significantly reduced all three of these processes, inhibiting generation of new cells. To determine the mechanisms relaying TH action in the SVZ, we analyzed which receptor was implicated and whether the effects were played out directly at the level of the stem cell population. The alpha TH receptor (TRalpha), but not TRbeta, was found to be expressed in nestin positive progenitor cells of the SVZ. Further, use of TRalpha mutant mice showed TRalpha to be required to maintain full proliferative activity. Finally, a direct TH transcriptional effect, not mediated through other cell populations, was revealed by targeted gene transfer to stem cells in vivo. Indeed, TH directly modulated transcription from the c-myc promoter reporter construct containing a functional TH response element containing TRE but not from a mutated TRE sequence. We conclude that liganded-TRalpha is critical for neurogenesis in the adult mammalian brain.}, Author = {Lemkine, and Raji, and Alfama, and Turque, and Hassani, and Alegria-Pr{\'e}vot, and Samarut, and Levi, and Demeneix,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8804484}, Pii = {04-2916fje}, Pubmed = {15728663}, Title = {Adult neural stem cell cycling in vivo requires thyroid hormone and its alpha receptor}, Uuid = {B998329D-CA79-476C-85CB-01E9527A0121}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.04-2916fje}} @article{Lendahl:1990, Abstract = {Multipotential CNS stem cells receive and implement instructions governing differentiation to diverse neuronal and glial fates. Exploration of the mechanisms generating the many cell types of the brain depends crucially on markers identifying the stem cell state. We describe a gene whose expression distinguishes the stem cells from the more differentiated cells in the neural tube. This gene was named nestin because it is specifically expressed in neuroepithelial stem cells. The predicted amino acid sequence of the nestin gene product shows that nestin defines a distinct sixth class of intermediate filament protein. These observations extend a model in which transitions in intermediate filament gene expression reflect major steps in the pathway of neural differentiation.}, Author = {Lendahl, U. and Zimmerman, L. B. and McKay, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Research Support, Non-U.S. Gov't;10 Development;Cell Differentiation;10 Hippocampus;Animals;RNA;Base Sequence;Rats;Cloning, Molecular;Comparative Study;Genes;Gene Library;Genetic Vectors;Cell Line;Research Support, U.S. Gov't, P.H.S.;Blotting, Northern;Intermediate Filament Proteins;Nucleotide Mapping;Amino Acid Sequence;Molecular Sequence Data;Nerve Tissue Proteins;Gene Expression;Sequence Homology, Nucleic Acid;Central Nervous System}, Medline = {90150286}, Month = {2}, Nlm_Id = {0413066}, Number = {4}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02142.}, Pages = {585-95}, Pii = {0092-8674(90)90662-X}, Pubmed = {1689217}, Title = {CNS stem cells express a new class of intermediate filament protein}, Uuid = {4380AEEE-7FED-11DA-9A2D-000D9346EC2A}, Volume = {60}, Year = {1990}} @article{Lennington:2003, Abstract = {Presumably, the 'hard-wired'neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ), which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL) of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis. 1477-7827 Journal article}, Author = {Lennington, J. B. and Yang, Z. and Conover, J. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Reprod Biol Endocrinol}, Keywords = {02 Adult neurogenesis migration;BB pdf;03 Adult neurogenesis progenitor source}, Number = {1}, Organization = {Center for Regenerative Biology and the Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA. joanne.conover\@uconn.edu}, Pages = {99}, Pubmed = {14614786}, Title = {Neural stem cells and the regulation of adult neurogenesis}, Uuid = {D8AFEBAB-31FF-4F2C-8889-48B3DC1027D7}, Volume = {1}, Year = {2003}, url = {papers/Lennington_ReprodBiolEndocrinol2003.pdf}} @article{Leonard:2007, Abstract = {Alzheimer's disease is a devastating neurological disorder. The role of hyperexcitability in the disease's cognitive decline is not completely understood. In this issue of Neuron, Palop et al. report both limbic seizures and presumed homeostatic responses to seizures in an animal model of Alzheimer's.}, Author = {Leonard, A. Soren and McNamara, James O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Animals;comment;Amyloid beta-Protein;Humans;21 Epilepsy;news;Epilepsy;Mutation;Homeostasis;Disease Models, Animal;Amyloid beta-Protein Precursor;Neuropeptide Y;Alzheimer Disease;21 Neurophysiology;Dentate Gyrus;24 Pubmed search results 2008;Neural Inhibition;Cognition Disorders}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA.}, Pages = {677-8}, Pii = {S0896-6273(07)00625-3}, Pubmed = {17785172}, Title = {Does epileptiform activity contribute to cognitive impairment in Alzheimer's disease?}, Uuid = {64465452-1A81-4271-AEA0-A8C433E49985}, Volume = {55}, Year = {2007}, url = {papers/Leonard_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.08.014}} @article{Leonardi-Essmann:2005, Abstract = {Fractalkine is the only known member of the CX(3)C-chemokine family, and so is its receptor CX(3)CR1. Fractalkine, typically is expressed by neurons where it is inserted in the plasma membrane ("chemokine on a stalk"). It can, however, be clipped off by a specific enzyme and diffuse into the extracellular space. CX(3)CR1 is primarily expressed by microglia, the phagocytes of the brain. This study was aimed at studying gene expression changes in cultured rat microglia upon fractalkine stimulation using gene chip technology. Six genes turned out to be upregulated, amongst which milk-fat globule EGF factor-8 protein (MFG-E8) was the most surprising, but also the most revealing one. We hypothesize that it serves as a bridging molecule between apoptotic cells (neurons) and microglia. Since the docking to microglia is, in part, mediated by members of the integrin family, six of these molecules have been-post hoc-included in real-time PCR confirmations of chip results. Two of them-integrin alpha(2) and integrin beta(5)-were upregulated as well. These data provide a much closer look into molecular mechanisms involved in apoptosis of neurons and their removal by microglia.}, Author = {Leonardi-Essmann, Fernando and Emig, Michael and Kitamura, Yoshihisa and Spanagel, Rainer and Gebicke-Haerter, Peter J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Alpha;11 Glia}, Month = {3}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Central Institute for Mental Health, Department of Psychopharmacology, J5, 68159 Mannheim, Germany.}, Pages = {92-101}, Pii = {S0165-5728(04)00415-1}, Pubmed = {15710462}, Title = {Fractalkine-upregulated milk-fat globule EGF factor-8 protein in cultured rat microglia}, Uuid = {D75E7423-E05A-486D-88CC-BCBC431F88C4}, Volume = {160}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneuroim.2004.11.012}} @article{Leonardo:2005, Abstract = {Zebra finch song is represented in the high-level motor control nucleus high vocal center (HVC) (Reiner et al., 2004) as a sparse sequence of spike bursts. In contrast, the vocal organ is driven continuously by smoothly varying muscle control signals. To investigate how the sparse HVC code is transformed into continuous vocal patterns, we recorded in the singing zebra finch from populations of neurons in the robust nucleus of arcopallium (RA), a premotor area intermediate between HVC and the motor neurons. We found that highly similar song elements are typically produced by different RA ensembles. Furthermore, although the song is modulated on a wide range of time scales (10-100 ms), patterns of neural activity in RA change only on a short time scale (5-10 ms). We suggest that song is driven by a dynamic circuit that operates on a single underlying clock, and that the large convergence of RA neurons to vocal control muscles results in a many-to-one mapping of RA activity to song structure. This permits rapidly changing RA ensembles to drive both fast and slow acoustic modulations, thereby transforming the sparse HVC code into a continuous vocal pattern.}, Author = {Leonardo, Anthony and Fee, Michale S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Muscles;research support, n.i.h., extramural ;Finches;Animals;Neural Pathways;Sound Spectrography;research support, u.s. gov't, p.h.s. ;research support, u.s. gov't, non-p.h.s. ;Brain;Time Factors;Male;research support, non-u.s. gov't ;Vocalization, Animal;Action Potentials;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Models, Neurological}, Month = {1}, Nlm_Id = {8102140}, Number = {3}, Organization = {McGovern Institute and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.}, Pages = {652-61}, Pii = {25/3/652}, Pubmed = {15659602}, Title = {Ensemble coding of vocal control in birdsong}, Uuid = {FC693F50-C685-40AC-956D-675B22DD57FC}, Volume = {25}, Year = {2005}, url = {papers/Leonardo_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3036-04.2005}} @article{Leonhard:2002, Abstract = {Resident macrophages of the peripheral nervous system have recently been shown to respond rapidly to Wallerian degeneration before the influx of blood-derived macrophages. Because resident endoneurial macrophages are slowly but incompletely exchanged from the blood within 3 months, they could potentially comprise a heterogenous cell population consisting of long-term resident cells and more mobile cells undergoing turnover. We used bone marrow chimeric mice created by transplanting bone marrow from green fluorescent protein-transgenic mice into irradiated wildtype recipients to selectively analyse the response of these two resident macrophage populations to Wallerian degeneration in sciatic nerve explant cultures. In such nerves, recently immigrated macrophages exhibit green fluorescence whereas long-term resident macrophages do not. Studies in cultures from wildtype controls revealed rapid morphological changes of resident macrophages towards a bloated phenotype, a proliferative response resulting in a 3.7-fold increase of macrophage numbers over 2 weeks, and phagocytosis of myelin basic protein-immunoreactive myelin debris. When chimeric mice were analysed, both populations of resident endoneurial macrophages participated in morphological transformation, proliferation and phagocytosis. Quantitative studies revealed a stronger proliferative and phagocytic response in long-term resident endoneurial macrophages compared with recently immigrated macrophages. Our results point towards subtle, but not principal, differences between the two macrophage populations, which might indicate different stages of macrophage differentiation rather than the existence of entirely distinct endoneurial macrophage populations. The results further underline the versatility of resident endoneurial macrophages following peripheral nerve injury, which is reminiscent of the lesion response of microglial cells within the brain.}, Author = {Leonhard, Christine and M{\"u}ller, Marcus and Hickey, William F. and Ringelstein, Erich B. and Kiefer, Reinhard}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Peripheral Nerves;Cell Differentiation;Animals;Phagocytosis;Macrophages;Bone Marrow Transplantation;Cell Count;Mice, Transgenic;Sciatic Nerve;Cell Movement;11 Glia;Organ Culture Techniques;Time Factors;Transplantation Chimera;Wallerian Degeneration;Mice;Cell Division;Immunohistochemistry;Histocompatibility Antigens Class II;Research Support, Non-U.S. Gov't}, Medline = {22318903}, Month = {11}, Nlm_Id = {8918110}, Number = {9}, Organization = {Department of Neurology, Universit{\"a}tsklinikum M{\"u}nster, Albert-Schweitzer-Str. 33, D-48129 M{\"u}nster, Germany.}, Pages = {1654-60}, Pii = {2236}, Pubmed = {12431217}, Title = {Lesion response of long-term and recently immigrated resident endoneurial macrophages in peripheral nerve explant cultures from bone marrow chimeric mice}, Uuid = {6675E6E0-52CA-486C-A687-D0C7C85BD1B8}, Volume = {16}, Year = {2002}} @article{Lerner-Tung:1995, Abstract = {Human endogenous retroviral sequences recently have been shown to be associated with breast cancer and some leukemias. These retroviral sequences have similarities to an endogenous retrovirus expressed in guinea pigs. The conditions for activation of this guinea pig retrovirus (GPRV) in cultured guinea pig embryo (GPE) cells using 5-bromo-2'-deoxyuridine (BrdU) was investigated. These studies employed the reverse transcriptase activity (RT) assay and electron microscopy (EM), in conjunction with Northern blot analysis that utilized a 2.6 kb GPRV-specific cDNA probe. Contrary to published studies, dexamethasone at concentrations ranging from 10(-8) to 10(-5) M appeared to play a minimal role in enhancing the production of GPRV. Following a 6 hr incubation with BrdU, GPRV mRNA was present in cultured GPE cells. Extracellular virion release was also observed by EM 12 hr later, although RT activity was not detected. All three methods detected viral expression at 48 hr after the addition of the drug. Additionally, after 6 hr exposure to BrdU, detectable RT and mRNA levels were maintained through 44 days after the removal of BrdU in a stationary culture condition and through 31 days in cultures that were subcultured weekly in media not containing BrdU. Low levels of extracellular viruses were detected in these cultures by electron microscopy through 49 days. Therefore, after only a 6 hr exposure to BrdU was extracellular GPRV detected 12 hr after drug removal and virus production continued for up to 49 days. This study provides information about an animal endogenous retroviral system that may be used as a model for the study of human endogenous retroviruses.}, Author = {Lerner-Tung, M. B. and Doong, S. L. and Cheng, Y. C. and Hsiung, G. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0920-8569}, Journal = {Virus Genes}, Keywords = {15 ERVs retroelements;15 Retrovirus mechanism;24 Pubmed search results 2008;Guinea Pigs;Microscopy, Electron;Retroviridae;Research Support, U.S. Gov't, P.H.S.;Research Support, U.S. Gov't, Non-P.H.S.;RNA, Viral;Dexamethasone;Virus Activation;Bromodeoxyuridine;Cells, Cultured;DNA, Complementary;Animals}, Medline = {95320966}, Month = {2}, Nlm_Id = {8803967}, Number = {3}, Organization = {Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT, USA.}, Pages = {201-9}, Pubmed = {7597799}, Title = {Characterization of conditions for the activation of endogenous guinea pig retrovirus in cultured cells by 5-bromo-2'-deoxyuridine}, Uuid = {833A1EEC-4326-11DB-A5D2-000D9346EC2A}, Volume = {9}, Year = {1995}} @article{Leroux:2002, Abstract = {Neuropeptide Y (NPY) is present in most cerebrocortical areas during fetal and postnatal development. In the rat frontal cortex, a dense radial fiber network containing NPY immunoreactivity is observed transiently as early as embryonic day 17 (E17) and disappears at the end of the first postnatal week. We have investigated the distribution of NPY receptors in the frontoparietal cortex at 13 stages of development, from E15 fetuses to adults, by in vitro autoradiography, using (125)I-pPYY as a radioligand. Quantitative receptor density was measured through all cortical layers at each developmental stage. Pharmacological identification of (125)I-pPPY binding sites was made by competition experiments using pNPY or [Leu(31),Pro(34)]pNPY and pNPY(13-36), as selective competitors for Y1 and Y2 receptors, respectively. NPY receptors were first detected in the cerebral cortex at low densities at E19 in a thin layer of tissue corresponding to the inner half of the intermediate zone (IZ) and the upper ventricular zone (VZ). The neuroepithelium did not contain binding sites. High densities of sites were observed by E21 onward to P10 in the deep cortical layers corresponding to the IZ and layers V-VI. A decreasing gradient of receptor density was observed from layer VI to the marginal zone (layer I). The distribution of NPY receptors does not match with the perikarya of transient NPY-immunoreactive neurons located in the cortical plate but does coincide with their axonal extension. The receptor density decreased abruptly between P10 and P12 in deep layers, whereas a moderate expression of binding sites is detected from P10 to P12 in layers I-III. By P14, the binding level was the lowest observed in the postnatal period. From P21 onward, receptors were observed in superficial layers I-III, and their density rose by two- to threefold up to adulthood. Competition studies indicated that the NPY receptors located in the deep cortical layers of the E21 or P1 rat cortex exhibit Y2 receptor type characteristics. The binding sites detected in the superficial layers from P10 to P12 rats also show Y2 receptors characteristics, unlike the NPY receptors in layers II-III of the adult, which behave like Y1 receptors. These data show that different NPY receptor types are successively expressed in specific layers during late gestation and early postnatal life in the rat frontoparietal cortex.}, Author = {Leroux, Philippe}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Fetus;Pregnancy;Cell Differentiation;Animals;Binding Sites;Radioligand Assay;Aging;Rats;Receptors, Neuropeptide Y;Peptide YY;Parietal Lobe;Frontal Lobe;Female;Iodine Radioisotopes;Rats, Wistar;Neuropeptide Y;Peptide Fragments;Animals, Newborn;Neurons;24 Pubmed search results 2008;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {21626275}, Month = {1}, Nlm_Id = {0406041}, Number = {1}, Organization = {Laboratory DIFEMA, UPRES EA 2122, Faculty of Medicine and Pharmacy, University of Rouen, 22 Boulevard Gambetta, 76183 Rouen, France. philippe.leroux\@univ-rouen.fr}, Pages = {35-47}, Pii = {10.1002/cne.1420}, Pubmed = {11754365}, Title = {Localization and characterization of NPY/PYY receptors in rat frontoparietal cortex during development}, Uuid = {9A2480BC-BECE-439E-B24F-B98DED371023}, Volume = {442}, Year = {2002}} @article{Letinic:2002, Abstract = {The mammalian neocortex contains two major classes of neurons, projection and local circuit neurons. Projection neurons contain the excitatory neurotransmitter glutamate, while local circuit neurons are inhibitory, containing GABA. The complex function of neocortical circuitry depends on the number and diversity of GABAergic (gamma-aminobutyric-acid-releasing) local circuit neurons. Using retroviral labelling in organotypic slice cultures of the embryonic human forebrain, we demonstrate the existence of two distinct lineages of neocortical GABAergic neurons. One lineage expresses Dlx1/2 and Mash1 transcription factors, represents 65\%of neocortical GABAergic neurons in humans, and originates from Mash1-expressing progenitors of the neocortical ventricular and subventricular zone of the dorsal forebrain. The second lineage, characterized by the expression of Dlx1/2 but not Mash1, forms around 35\%of the GABAergic neurons and originates from the ganglionic eminence of the ventral forebrain. We suggest that modifications in the expression pattern of transcription factors in the forebrain may underlie species-specific programmes for the generation of neocortical local circuit neurons and that distinct lineages of cortical interneurons may be differentially affected in genetic and acquired diseases of the human brain. 0028-0836 Journal Article}, Author = {Letinic, K. and Zoncu, R. and Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Nature}, Keywords = {Interneurons/cytology/metabolism/ultrastructure;Human;Neocortex/*cytology/embryology/*metabolism/ultrastructure;In Vitro;DNA-Binding Proteins/analysis;Stem Cells/cytology/metabolism/ultrastructure;Transcription Factors/analysis;Proteoglycans;Cell Movement;Drug Combinations;gamma-Aminobutyric Acid/*metabolism;*Cell Lineage;Neurons/*cytology/*metabolism/ultrastructure;Laminin;Species Specificity;H abstr;Homeodomain Proteins/analysis;Pyramidal Cells/cytology/metabolism;Cell Division;Immunohistochemistry;Microscopy, Electron;Biological Markers/analysis;Collagen;12 Interneuron development}, Number = {6889}, Organization = {Yale University School of Medicine, Section of Neurobiology, New Haven, Connecticut 06510, USA.}, Pages = {645-9}, Pubmed = {12050665}, Title = {Origin of GABAergic neurons in the human neocortex}, Uuid = {889A0D0D-94EE-426D-A9B3-BF2E308C6EC6}, Volume = {417}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12050665}} @article{Levesque:1996, Abstract = {Corticostriatal projections arising from the infragranular layers of the motor and second somatosensory cortices were studied in rats after labeling small pools of neurons with biocytin. Camera lucida reconstruction of 263 fibers arising from laminae V and VI revealed that all corticostriatal projections derive from collaterals of lamina V cells whose main axons descend into the cerebral peduncle. In contrast, lamina VI cells do not branch upon the striatum, but upon the thalamus. Together with the results obtained in previous tracing studies, the present data raise the possibility that no neuron is exclusively corticostriatal. We therefore propose that all corticostriatal projections are collaterals given off by the axons of two types of neurons: layer V cells whose main axon project to the brainstem and/or spinal cord, and layer III cells that project to the contralateral hemisphere.}, Author = {Levesque, M. and Charara, A. and Gagnon, S. and Parent, A. and Deschenes, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {research support, non-u.s. gov't;Rats, Sprague-Dawley;21 Neurophysiology;Female;Motor Cortex;Rats;Corpus Striatum;Lysine;Brain Mapping;Synaptic Transmission;Somatosensory Cortex;Animals;Male;Thalamus;24 Pubmed search results 2008;Axons}, Month = {2}, Nlm_Id = {0045503}, Number = {2}, Organization = {Centre de Recherche en Neurobiologie, Hopital de l'Enfant-Jesus, Universite Laval, Quebec, Canada.}, Pages = {311-5}, Pii = {0006-8993(95)01333-4}, Pubmed = {8833768}, Title = {Corticostriatal projections from layer V cells in rat are collaterals of long-range corticofugal axons}, Uuid = {587F268F-4EBC-4ADF-8B1B-985916D5291B}, Volume = {709}, Year = {1996}, url = {papers/Levesque_BrainRes1996.pdf}} @article{Levine:2004, Abstract = {Autophagy is the major cellular pathway for the degradation of long-lived proteins and cytoplasmic organelles. It involves the rearrangement of subcellular membranes to sequester cargo for delivery to the lysosome where the sequestered material is degraded and recycled. For many decades, it has been known that autophagy occurs in a wide range of eukaryotic organisms and in multiple different cell types during starvation, cellular and tissue remodeling, and cell death. However, until recently, the functions of autophagy in normal development were largely unknown. The identification of a set of evolutionarily conserved genes that are essential for autophagy has opened up new frontiers for deciphering the role of autophagy in diverse biological processes. In this review, we summarize our current knowledge about the molecular machinery of autophagy and the role of the autophagic machinery in eukaryotic development.}, Author = {Levine, Beth and Klionsky, Daniel J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {1534-5807}, Journal = {Dev Cell}, Keywords = {10 Structural plasticity;10 Development;Research Support, Non-U.S. Gov't;Protein Transport;Cell Aging;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;Eukaryotic Cells;Lysosomes;review, tutorial;Cell Death;Humans;Peptide Hydrolases;Animals;review;Autophagocytosis}, Month = {4}, Nlm_Id = {101120028}, Number = {4}, Organization = {Department of Medicine, Columbia University, New York, NY 10032, USA. levine\@cancercenter.columbia.edu}, Pages = {463-77}, Pii = {S1534580704000991}, Pubmed = {15068787}, Title = {Development by self-digestion: molecular mechanisms and biological functions of autophagy}, Uuid = {F3FC63AA-DAC6-4B9C-BF80-B35D939DE827}, Volume = {6}, Year = {2004}} @article{Levison:1998, Abstract = {Studies using transgenic mice that overexpress ciliary neurotrophic factor (CNTF), direct injection of CNTF into brain parenchyma, and ectopic expression of CNTF by an adenoviral vector have demonstrated that CNTF activates astrocytes. Paradoxically, studies to date have failed to show an effect of CNTF on the expression of GFAP by cultured astrocytes. Therefore, the goal of this study was to use nuclear hypertrophy and GFAP expression as indices of glial activation to compare the responsiveness of forebrain type 1 and type 2 astrocytes to CNTF. As reported by others, CNTF did not increase GFAP in type 1 astrocytes; however, it rapidly increased their nuclear size by 20\%. Nuclear hypertrophy was apparent within 4 h after CNTF exposure and persisted for at least 48 h. In contrast, type 2 astrocyte GFAP increased 2-fold over the course of 48 h of CNTF treatment. During this same treatment period type 2 astroglial nuclei enlarged by 25\%. We conclude that CNTF stimulates both type 1 and type 2 astrocytes directly. Together with our in vivo studies (Levison et al., 1996: Exp. Neurol. 141: 256), these data support the concept that CNTF is responsible for many of the progressive astroglial changes that appear after CNS injury and disease. 98398397 0006-8993 Journal Article}, Author = {Levison, S. W. and Hudgins, S. N. and Crawford, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Brain Res}, Keywords = {Ciliary Neurotrophic Factor;Prosencephalon/cytology;Rats;Nerve Tissue Proteins/*pharmacology;G abstr;Astrocytes/*drug effects/pathology;Animal;11 Glia;Glial Fibrillary Acidic Protein/*metabolism;Nerve Growth Factors/pharmacology;Animals, Newborn;Support, Non-U.S. Gov't;Cells, Cultured;Cell Nucleus/drug effects/*pathology;Hypertrophy}, Number = {1-2}, Organization = {Department of Neuroscience and Anatomy, H109, Pennsylvania State University, College of Medicine, P.O. Box 850, Hershey, PA 17033, USA. slevison\@psu.edu}, Pages = {189-93}, Pubmed = {9729376}, Title = {Ciliary neurotrophic factor stimulates nuclear hypertrophy and increases the GFAP content of cultured astrocytes}, Uuid = {1851C11A-9D18-4702-AFCC-EE1BAAF8CE42}, Volume = {803}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9729376}} @article{Levison:2000, Abstract = {During development, the output of the subventricular zone (SZ) becomes increasingly restricted, yet it still harbors multipotential progenitors. The output of the SZ could be gated by selectively eliminating inappropriately specified progenitors. Using in situ end- labeling (ISEL) to identify apoptotic cells, nearly 60\%of the ISEL(+) cells in the juvenile forebrain were localized to the SZ. Of these dying cells, at least 9\%could be identified as neurons, 4\%as astrocytes, and 12\%as oligodendrocytes. The remainder were negative for the stem cell marker nestin, as well as other markers evaluated. To test the hypothesis that committed progenitors were under selective pressures, neural stem/progenitor cells were allowed to differentiate in vitro in the presence or absence of the caspase 3 inhibitor z-DEVD- fmk. DEVD increased neuronal production 10-fold over control cultures. By contrast, the development of astrocytes and oligodendrocytes was not affected. Altogether, these data support the hypothesis that selective forces within the postnatal rat forebrain control the types of precursors that emerge from the germinal matrix. Furthermore, they suggest that different mechanisms control neuronal versus glial cell numbers. Using Smart Source Parsing}, Author = {Levison, S. W. and Rothstein, R. P. and Brazel, C. Y. and Young, G. M. and Albrecht, P. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Dev Neurosci}, Keywords = {Cell Differentiation/drug effects;Rats;Apoptosis/*physiology;Animal;Ependyma/cytology/*physiology;02 Adult neurogenesis migration;Enzyme Inhibitors/pharmacology;Rats, Sprague-Dawley;Stem Cells/cytology/metabolism;03 Adult neurogenesis progenitor source;Cell Line;Caspases/antagonists &inhibitors;BB pdf;In Situ Nick-End Labeling;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Animals, Newborn/physiology;Neuroglia/metabolism;Neurons/cytology/metabolism;Biological Markers}, Number = {1-2}, Organization = {Department of Neuroscience, Pennsylvania State University College of Medicine, Hershey, Pa., USA. slevison\@psu.edu}, Pages = {106-15}, Title = {Selective apoptosis within the rat subependymal zone: a plausible mechanism for determining which lineages develop from neural stem cells}, Uuid = {252D46F1-C3CE-4541-B594-5B6A10791A99}, Volume = {22}, Year = {2000}, url = {papers/Levison_DevNeurosci2000}} @article{Levison:2001, Abstract = {Cerebral hypoxia/ischemia of the newborn has a frequency of 4/1,000 births and remains a major cause of cerebral palsy, epilepsy, and mental retardation. Despite progress in understanding the pathogenesis of hypoxic-ischemic injury, the data are incomplete regarding the mechanisms leading to permanent brain injury. Here we tested the hypothesis that cerebral hypoxia/ischemia damages stem/progenitor cells in the subventricular zone (SVZ), resulting in a permanent depletion of oligodendrocytes. We used a widely accepted rat model and examined animals at recovery intervals ranging from 4 h to 3 weeks. Within hours after the hypoxic-ischemic insult 20\%of the total cells were deleted from the SVZ. The residual damaged cells appeared necrotic. During 48 h of recovery deaths accumulated; however, these later deaths were predominantly apoptotic. Many apoptotic SVZ cells stained with a marker for immature oligodendrocytes. At 3 weeks survival, the SVZ was smaller and markedly less cellular, and it contained less than 1/4 the normal complement of neural stem cells. The corresponding subcortical white matter was dysmyelinated, relatively devoid of oligodendrocytes and enriched in astrocytes. We conclude that neural stem cells and oligodendrocyte progenitors in the SVZ are vulnerable to hypoxia/ischemia. Consequently, the developmental production of oligodendrocytes is compromised and regeneration of damaged white matter oligodendrocytes does not occur resulting in failed regeneration of CNS myelin in periventricular loci. The resulting dysgenesis of the brain that occurs subsequent to perinatal hypoxic/ischemic injury may contribute to the cognitive and motor dysfunction that results from asphyxia of the newborn. 21481710 0378-5866 Journal Article}, Author = {Levison, S. W. and Rothstein, R. P. and Romanko, M. J. and Snyder, M. J. and Meyers, R. L. and Vannucci, S. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Dev Neurosci}, Keywords = {Cerebrovascular Accident/pathology;Hypoxia-Ischemia, Brain/*pathology;G abstr;Female;Rats;Apoptosis;Rats, Wistar;Animal;11 Glia;Pregnancy;Cerebral Ventricles/*embryology/pathology;Support, U.S. Gov't, P.H.S.;Cerebral Palsy/pathology;Neurons/*pathology;Oligodendroglia/*pathology;Stem Cells/*pathology}, Number = {3}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey, Pa 17033, USA. slevison\@psu.edu}, Pages = {234-47}, Pubmed = {11598326}, Title = {Hypoxia/ischemia depletes the rat perinatal subventricular zone of oligodendrocyte progenitors and neural stem cells}, Uuid = {5A825527-5F6B-44D3-9223-75271E34B105}, Volume = {23}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11598326}} @article{Levison:2003, Abstract = {The developmental origin of microglia remains a controversial subject. While it is generally accepted that primitive fetal macrophages that migrate from the yolk sac to the brain become microglia, it also has been argued that there is a second source of microglia that are of neuroectodermal lineage. To determine whether progenitors in the dorsolateral subventricular zone (SVZDL) are capable of producing microglia as well as macroglia, we infected perinatal rat SVZDL cells with a mixture of two replication-deficient retroviruses, placed these progenitors in vitro and then varied the media formulations to promote microglial differentiation. Mixed macroglial clones were obtained, but no heterogeneous clones containing microglia were observed, regardless of the media components. Among the macroglial clones, we observed every possible combination of type 1 astrocyte and O-2A lineage cells. Some clones were homogeneous and contained cells belonging to a single macroglial lineage. Other clonal clusters were heterogeneous and were comprised of type 1 astrocytes and oligodendrocytes, type 1 and type 2 astrocytes, or type 2 astrocytes and oligodendrocytes. Of 130 clones examined, where we used triple immunofluorescence with antibodies that recognize microglia, 2 clonal clusters contained OX-42+ microglia that were retrovirally labeled, but all of the cells in those clones expressed the microglial marker and none expressed either GFAP or O4. In addition, we isolated neural stem cells from the perinatal SVZDL and assessed their capacity to generate macroglia and microglia. Confirming and extending our previous analyses, neural stem cells generated homogeneous and heterogeneous macroglial clones, but they did not generate microglia. We conclude that brain macroglia and microglia do not share a common precursor, even though the neural stem cells in the SVZDL cells can produce neurons, astrocytes and oligodendrocytes. Therefore, the microglia that reside in the SVZDL are immigrants from nonneural precursors. 0378-5866 Journal Article}, Author = {Levison, S. W. and Druckman, S. K. and Young, G. M. and Basu, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Dev Neurosci}, Keywords = {Glial Fibrillary Acidic Protein/metabolism;Animals;Astrocytes/*cytology;Rats;Fluorescent Antibody Technique;Genetic Vectors/administration &dosage;02 Adult neurogenesis migration;Oligodendroglia/*cytology;Stem Cells/*cytology/drug effects;11 Glia;Retroviridae;Interleukin-6/pharmacology;Injections, Intraventricular;03 Adult neurogenesis progenitor source;Brain/*cytology/growth &development;BB pdf;Cell Lineage/physiology;Membrane Glycoproteins/metabolism;Support, U.S. Gov't, P.H.S.;Cell Differentiation/physiology;Immunohistochemistry;Antigens, CD45/metabolism;Clone Cells;Microglia/*cytology/metabolism}, Number = {2-4}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey, PA 17033, USA. slevinson\@psu.edu}, Pages = {184-96}, Pubmed = {12966216}, Title = {Neural stem cells in the subventricular zone are a source of astrocytes and oligodendrocytes, but not microglia}, Uuid = {D2D212D4-1833-401F-B110-F651D5818703}, Volume = {25}, Year = {2003}, url = {papers/Levison_DevNeurosci2003.pdf}} @article{Levison:1993, Abstract = {Postnatal gliogenesis in the rodent forebrain was studied by infecting subventricular zone cells of either neonates or juvenile rats with replication-deficient retroviruses that encode reporter enzymes, enabling the migration and fate of these germinal zone cells to be traced over the ensuing several weeks. Neither neonatal nor juvenile subventricular zone cells migrated substantially along the rostral-caudal axis. Neonatal subventricular zone cells migrated dorsally and laterally into hemispheric gray and white matter and became both astrocytes and oligodendrocytes. Juvenile subventricular zone cells migrated into more medial areas of the subcortical white matter and on occasion appeared in the white matter of the contralateral hemisphere, but rarely migrated into the neocortex. Juvenile subventricular zone cells almost exclusively differentiated into oligodendrocytes. Thus, the migratory patterns and the developmental fates of subventricular zone cells change during the first 2 weeks of life. When either neonatal or juvenile subventricular zone cells were labeled in vivo and then removed and cultured, some generated homogeneous clones that contained either astrocytes with a 'type 1'phenotype or oligodendrocytes, but some generated heterogeneous clones that contained both glial types. These results provide additional evidence for a common progenitor for astrocytes and oligodendrocytes and strongly suggest that temporally and spatially regulated environmental signals control the destiny of glial progenitors during postnatal development. eng Journal Article}, Author = {Levison, S. W. and Chuang, C. and Abramson, B. J. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Development}, Keywords = {Neuroglia/*physiology;Rats, Sprague-Dawley;G abstr;Rats;Brain/*growth &development;Time Factors;Retroviridae;Cell Differentiation/physiology;11 Glia;Animal;Support, U.S. Gov't, P.H.S.;Histocytochemistry;Oligodendroglia/physiology;Cells, Cultured;Astrocytes/physiology;Cell Movement/physiology}, Number = {3}, Organization = {Department of Pathology, Columbia University College of Physicians and Surgeons, New York, NY 10032.}, Pages = {611-22.}, Title = {The migrational patterns and developmental fates of glial precursors in the rat subventricular zone are temporally regulated}, Uuid = {A5A23E87-BD3C-45F4-BD74-B7A17987F05D}, Volume = {119}, Year = {1993}, Bdsk-Url-1 = {http://www.cob.org.uk/Development/119/03/dev4131.html}} @article{Levison:1996, Abstract = {CNS trauma or disease induces a constellation of changes in the glia comprising the condition known as reactive gliosis. At present, little is known regarding the nature of the injury signals and the specific consequences of their actions. Ciliary neurotrophic factor (CNTF) induces acute phase proteins in liver and increases astrocytic glial fibrillary acidic protein (GFAP) both in vitro and in vivo. The purpose of the present study was to establish whether CNTF induces other aspects of gliosis. Between 10 and 72 h after 100 ng of recombinant human CNTF was administered into the adult rat neocortex, alterations were observed in a region extending several millimeters in circumference from the injection site. Microglia in this region were more apparent and astrocytes were hypertrophic. By in situ hybridization, mRNAs for GFAP, vimentin, and clusterin were upregulated when compared to the control hemisphere (which received heat-inactivated CNTF). By immunocytochemistry, GFAP, vimentin, glutathione-S-transferase mu, S-100, and OX-42 were elevated by 48 h. By contrast, the oligodendroglial marker GSTYp, the neuronal markers MAP-2 and NSE, the intermediate filament nestin, and the stress protein alpha B-crystallin were unchanged. In addition, a greater than twofold increase in the number of proliferating cells was observed. Since CNTF induces swelling and multiple "gliotic"genes in astrocytes, increases microglial number, and stimulates cell proliferation, we conclude that CNTF is sufficient to induce multiple aspects of gliosis. These data are consistent with a model whereby CNTF (which is synthesized by astrocytes) would be released when the integrity of the astrocyte membrane is compromised, whereupon it would elicit an inflammatory response. 96424473 0014-4886 Journal Article}, Author = {Levison, S. W. and Ducceschi, M. H. and Young, G. M. and Wood, T. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Exp Neurol}, Keywords = {In Situ Hybridization;Rats, Sprague-Dawley;Ciliary Neurotrophic Factor;G abstr;Human;Nerve Tissue Proteins/*pharmacology;Rats;RNA, Messenger/metabolism;Female;Autoradiography;11 Glia;Animal;Nerve Growth Factors/*pharmacology;Support, Non-U.S. Gov't;Gliosis/*chemically induced}, Number = {2}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey 17033, USA. Slevison\@Neuro.hmc.psu.edu}, Pages = {256-68}, Pubmed = {8812159}, Title = {Acute exposure to CNTF in vivo induces multiple components of reactive gliosis}, Uuid = {2116B247-4499-4572-8FFF-174BBA8DC9CA}, Volume = {141}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8812159}} @article{Levison:2000a, Abstract = {Proliferating astrocytes are frequently observed in diseased and injured brains. These newly generated astrocytes are necessary to reestablish the barriers that isolate the CNS from the rest of the body; however, they also create a matrix that inhibits regeneration and remyelination. Therefore, it is important to understand the mechanisms that enable a terminally differentiated astrocyte to reenter the cell cycle. Ciliary neurotrophic factor (CNTF), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), and fibroblastic growth factor-2 (FGF-2) are four cytokines that are rapidly elevated in damaged neural tissue. These cytokines also have been implicated in glial scar formation. We sought to determine whether IL-6 and CNTF stimulate astroglial proliferation alone or in combination with other mitogens. Intraparenchymal CNTF modestly increased the number of proliferating cell nuclear antigen (PCNA) and glial fibrillary acidic protein (GFAP) double positive astrocytes when introduced by stereotactic injection into the adult rat brain. When applied directly to highly enriched rat forebrain astrocyte cultures, neither CNTF nor IL-6-stimulated DNA synthesis. Therefore, they are not astroglial mitogens. However, both cytokines synergized with epidermal growth factor (EGF), increasing its mitogenicity by approximately twofold. Astrocytes that had been "aged"for at least 3 weeks in vitro became refractory to EGF; however, when these "aged"astrocytes were pretreated with either IL-6 or CNTF for as little as 2 h, they became competent to reenter the cell cycle upon exposure to EGF. These data suggest that IL-6 type cytokines, likely by activating STAT family transcription factors, induce the expression of signaling molecules that endow resting astrocytes with the competence to respond to mitogens and to reenter the cell cycle. 20556184 0894-1491 Journal Article}, Author = {Levison, S. W. and Jiang, F. J. and Stoltzfus, O. K. and Ducceschi, M. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Glia}, Keywords = {*Interleukin-6;Proliferating Cell Nuclear Antigen/analysis;Prosencephalon/cytology;Cells, Cultured;Rats;Microtubule-Associated Proteins/analysis;Ciliary Neurotrophic Factor/*pharmacology;Thymidine/pharmacokinetics;Astrocytes/chemistry/*cytology/*drug effects;Animal;Epidermal Growth Factor/*pharmacology;Rats, Sprague-Dawley;Glial Fibrillary Acidic Protein/analysis;G abstr;11 Glia;DNA/biosynthesis;Support, Non-U.S. Gov't;Tritium/diagnostic use;Fibroblast Growth Factor 2/pharmacology;Cell Division/drug effects}, Number = {3}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA. slevison\@psu.edu}, Pages = {328-37}, Pubmed = {11102972}, Title = {IL-6-type cytokines enhance epidermal growth factor-stimulated astrocyte proliferation}, Uuid = {27010CBB-9161-40EE-84C4-7434E5BDF942}, Volume = {32}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11102972}} @article{Levison:1991, Abstract = {Studies on glial cultures have demonstrated that fetal bovine serum contains a factor that induces bipotential glial precursors known as oligodendrocyte-type 2 astrocyte (O-2A) progenitors to become type 2 astroglia rather than oligodendroglia. The goal of this research project was to characterize and purify this factor, which we refer to as the astroglia-inducing molecule (AIM). Using cultures enriched in O-2A progenitors, we determined that AIM is present in human and bovine sera and that fetal bovine serum qualified as the best serum for purifying AIM. AIM is heat and trypsin labile and may be a plasma glycoprotein. A 240-fold enriched AIM preparation was produced by applying an ammonium sulfate precipitate of fetal bovine serum to heparin and then lentil lectin-agarose, followed by gel filtration chromatography. In crude preparations, AIM activity migrated at 50 kDa by gel filtration. With enrichment, activity was seen at several molecular masses, all of which were approximate multiples of 50 kDa. Treatment with 6 M guanidine hydrochloride generated an AIM with a molecular mass between 12 and 18 kDa, a result suggesting that AIM aggregates. On a preparative isoelectric focusing gel, AIM activity most frequently migrated between pH values of 3 and 4; however, proteins with isoelectric points of greater than 9 or at 6 also had activity in several experiments. These data suggest that either multiple AIMs exist or that a single AIM exists that associates with other proteins. Immunofluorescence for ganglioside GD3 and glial fibrillary acidic protein confirmed that AIM preparations induce type 2 astroglia from O-2A progenitors and suggests that AIM has little effect on type 1 astroglia. Because none of the known growth factors that have been tested to date mimics its effects. AIM may be a novel differentiation factor. 91318280 0022-3042 Journal Article}, Author = {Levison, S. W. and McCarthy, K. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurochem}, Keywords = {Support, U.S. Gov't, P.H.S.;Blood Proteins/*analysis/isolation &purification/physiology;Fluorescent Antibody Technique;G abstr;Rats;Astrocytes/*cytology/drug effects;Stem Cells/*cytology/drug effects;11 Glia;Animal;Cerebral Cortex/*cytology;Cell Differentiation/drug effects/physiology;Neuroglia/*cytology/drug effects;Cells, Cultured;Isoelectric Focusing;Hydrogen-Ion Concentration;Chromatography, Gel;Serum Albumin, Bovine/pharmacology}, Number = {3}, Organization = {Curriculum in Neurobiology, University of North Carolina, Chapel Hill 27599-7369.}, Pages = {782-94}, Pubmed = {1861150}, Title = {Characterization and partial purification of AIM: a plasma protein that induces rat cerebral type 2 astroglia from bipotential glial progenitors}, Uuid = {B0BEA641-2721-4011-80BE-C7593F35193A}, Volume = {57}, Year = {1991}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1861150}} @article{Levison:1989, Abstract = {Cultured rat dorsal root ganglion neurons expressed ganglioside GD3 when grown in the absence of non-neuronal cells. Among the non-neuronal cells, fibroblasts, but not Schwann cells, also stained for ganglioside GD3 during the first few days in culture. When neurons were combined with non-neuronal cells the intensity of the GD3 immunoreactive neuronal processes was diminished at sites contacted by Schwann cells. This contact-mediated effect was specific for ganglioside GD3 since no difference was seen with A2B5 or JONES antibodies, which recognize different gangliosides. 90037545 0165-5728 Journal Article}, Author = {Levison, S. W. and McCarthy, K. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neuroimmunol}, Keywords = {Schwann Cells/*metabolism;G abstr;Rats;Antibodies, Monoclonal;Gangliosides/*analysis;Animal;11 Glia;Sciatic Nerve/cytology;Ganglia, Spinal/cytology/*metabolism;Neurons/metabolism;Cells, Cultured;Support, U.S. Gov't, P.H.S.;Rats, Inbred Strains;Fluorescent Antibody Technique}, Number = {3}, Organization = {Curriculum in Neurobiology, University of North Carolina, Chapel Hill 27599.}, Pages = {223-32}, Pubmed = {2681262}, Title = {Schwann cells influence the expression of ganglioside GD3 by rat dorsal root ganglion neurons}, Uuid = {8BC486A3-69B0-4E22-A32C-EFE77307A39C}, Volume = {24}, Year = {1989}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2681262}} @article{Levison:1997, Abstract = {Developmental studies have shown that both neurons and glia arise from the subventricular zone (SVZ) but there have been no clonal analyses to determine whether a single progenitor can produce both. Therefore, we used replication deficient retroviral vectors to analyze the clonal progeny of single rat SVZ cells that were maintained in culture media permissive or non-permissive for neuronal differentiation. When maintained in medium supplemented with 5\%fetal bovine serum, all surviving progenitors generated glial cell clones. Within these glial clones we often observed both type 1 astrocytes and O-2A lineage cells. When SVZ cells were maintained in medium permissive for neurogenesis approximately 50\%of the total clones contained at least one antigenically defined neuron. Of those clones that contained neurons, 60\%contained neurons and glia. The other 50\%of the total clones were either comprised of only astrocytes, astrocytes and oligodendrocytes, or were unidentifiable. Since the culture environment permitted multilineage clone formation, yet many homogeneous neuronal or astrocytic clones were obtained, some progenitors must become developmentally restricted while they are in the germinal zone. Therefore, we conclude that the perinatal SVZ is a mosaic of multipotential, bipotential, and lineage restricted precursors, and that the lack of postnatal neocortical neurogenesis is not due to the absence of potential neuroblasts. 97276384 0360-4012 Journal Article}, Author = {Levison, S. W. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurosci Res}, Keywords = {Cell Adhesion Molecules, Neuronal/analysis/immunology;Cerebral Ventricles/*cytology;Microtubule-Associated Proteins/analysis/immunology;Cells, Cultured;Rats;Fluorescent Antibody Technique;Vimentin/analysis/immunology;Stem Cells/chemistry/*cytology;Neurons/chemistry/*cytology;Animal;Astrocytes/chemistry/*cytology;Mammals;Rats, Sprague-Dawley;11 Glia;G abstr;Retroviridae;Oligodendroglia/chemistry/*cytology;Glial Fibrillary Acidic Protein/analysis/immunology;Animals, Newborn;Antibodies, Monoclonal;Lac Operon;Cell Lineage/physiology;Support, U.S. Gov't, P.H.S.;Cell Differentiation/physiology;Genes, Reporter;Biological Markers;Intermediate Filament Proteins/analysis/immunology}, Number = {2}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey, USA.}, Pages = {83-94}, Pubmed = {9130137}, Title = {Multipotential and lineage restricted precursors coexist in the mammalian perinatal subventricular zone}, Uuid = {59F6AA47-E68C-42CC-B64E-B21741FD9DCF}, Volume = {48}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9130137}} @article{Levison:1999, Abstract = {Gliogenesis in the mammalian central nervous system does not cease abruptly like neurogenesis. Instead, glia accumulate over a time period that extends into adulthood. To determine whether new glial cells in the adult cortex arise from resident progenitors and to determine the glial types to which these progenitors give rise to, cells in the perinatal subventricular zone (SVZ) were labeled with replication- deficient retroviral vectors, and clonal clusters of glia in the neocortex were examined from 1 week to 8 months of age. The average clonal cluster size increased during the first month of life. Interestingly, clusters containing oligodendrocyte lineage cells preferentially expanded with age, on average doubling every 3 months. Unexpectedly, the number of cells in astrocyte clusters decreased over time. In heterogeneous clusters, the numbers of oligodendroglia increased, whereas the number of astrocytes did not. Moreover, clonal clusters containing mature glia also contained less mature cells, indicating that clonally related progenitors do not differentiate synchronously in vivo. Thus, progenitors from the SVZ continue to cycle, resulting in an accumulation of oligodendroglia in the neocortex. These slowly cycling cells likely express the NG2 proteoglycan because a subset of the clonal clusters contained NG2(+) cells and these NG2(+) cells accumulated with time.}, Author = {Levison, S. W. and Young, G. M. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurosci Res}, Keywords = {Oligodendroglia/*cytology;02 Adult neurogenesis migration;Rats, Sprague-Dawley;B-11;Rats;Clone Cells/physiology;Cell Cycle/*physiology;Animal;Support, U.S. Gov't, P.H.S.;Cell Aging/*physiology;Neocortex/*cytology;Support, Non-U.S. Gov't;Stem Cells/physiology;Cell Movement/physiology}, Number = {4}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State College of Medicine, Hershey 17033, USA. slevison\@psu.edu}, Pages = {435-46.}, Title = {Cycling cells in the adult rat neocortex preferentially generate oligodendroglia}, Uuid = {2468AEEF-692C-4C25-9A4E-359D79B53940}, Volume = {57}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10440893}} @article{Levison:1993a, Abstract = {The developmental fates of subventricular zone (SVZ) cells of the postnatal rat forebrain were determined by retroviral-mediated gene transfer and immunolabeling for glial antigens. A beta-galactosidase- containing retrovirus injected stereotactically into the SVZ infected small, immature cells. By 28 days post-injection labeled cells had appeared in both gray and white matter of the ipsilateral hemisphere. White matter contained labeled oligodendrocytes, but few astrocytes, while neocortex and striatum contained both glial types, often appearing in tightly knit clusters. An analysis after simultaneously injecting alkaline phosphatase- and beta-galactosidase-containing retroviruses showed that cells in each cortical cluster were related. Most clusters contained a single cell type, but approximately 15\%contained both astrocytes and oligodendrocytes. These observations strongly suggest that a single SVZ cell can differentiate into both glial types.}, Author = {Levison, S. W. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Neuron}, Keywords = {Prosencephalon/*cytology;Stereotaxic Techniques;Rats;Transfection;*Cell Differentiation;Fluorescent Antibody Technique;beta-Galactosidase/analysis/genetics;Animal;Rats, Sprague-Dawley;G abstr;11 Glia;Stem Cells/*cytology;Astrocytes/*cytology/enzymology;Retroviridae/genetics;Histocytochemistry;Support, U.S. Gov't, P.H.S.;Oligodendroglia/*cytology/enzymology;Gene Expression;Alkaline Phosphatase/analysis/genetics;Genetic Markers}, Number = {2}, Organization = {Department of Pathology, Columbia University College of Physicians and Surgeons, New York, New York 10032.}, Pages = {201-12}, Title = {Both oligodendrocytes and astrocytes develop from progenitors in the subventricular zone of postnatal rat forebrain}, Uuid = {E7A4F69A-EE2B-11DA-8605-000D9346EC2A}, Volume = {10}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8439409}} @article{Levitt:2005, Abstract = {Advances in defining mechanisms of cortical development have been paralleled in recent years by an intense interest in translating these findings into greater insight of both childhood- and adult-onset cognitive and mental health disorders of developmental etiology. Successful integration of basic and clinical findings have been applied to monogenic disorders. The greater challenge lies in studying cortical development in the context of gene x environment interactions, which underlie the pathogenesis of the most common neurodevelopmental disorders. This can occur through an improved delineation of pathophysiological characteristics unique to specific complex disorders and the application of this information to the refinement of the most relevant model systems.}, Author = {Levitt, Pat}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee 37203, USA. pat.levitt\@vanderbilt.edu}, Pages = {407-12}, Pii = {S0896-6273(05)00351-X}, Pubmed = {15882640}, Title = {Developmental neurobiology and clinical disorders: lost in translation?}, Uuid = {A81A5B8C-2765-4410-9BB3-EEFEAB64F764}, Volume = {46}, Year = {2005}, url = {papers/Levitt_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.015}} @article{Lewis:1994, Abstract = {The human immunodeficiency virus productively infects and integrates into cells that have been arrested in the cell cycle with either gamma irradiation or aphidicolin. Integration by oncoretroviruses such as the murine leukemia virus (MuLV), on the other hand, depends on cell proliferation. Although the entire cell cycle is not necessary for MuLV infection, it is essential that the infected cells pass through mitosis. The long terminal repeat circle junction, a marker for nuclear entry, is first observed in MuLV-infected cells immediately after mitosis. These results suggest that mitosis is necessary for nuclear entry of MuLV, but not human immunodeficiency virus, unintegrated proviral DNA.}, Author = {Lewis, P. F. and Emerman, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Base Sequence;HIV-1;DNA, Circular;Research Support, Non-U.S. Gov't;S Phase;Comparative Study;Molecular Sequence Data;Research Support, U.S. Gov't, P.H.S.;Hela Cells;Aphidicolin;DNA, Viral;Mitosis;DNA, Complementary;Humans;15 Retrovirus mechanism;Leukemia Virus, Murine;Genetic Vectors}, Medline = {94076446}, Month = {1}, Nlm_Id = {0113724}, Number = {1}, Organization = {Department of Pediatrics, University of Washington, Seattle.}, Pages = {510-6}, Pubmed = {8254763}, Title = {Passage through mitosis is required for oncoretroviruses but not for the human immunodeficiency virus}, Uuid = {E18BE20E-DFC2-11DA-AC55-000D9346EC2A}, Volume = {68}, Year = {1994}} @article{Lewis:2005, Abstract = {PURPOSE: To compare the activation of microglia in response to retinal detachment in four species. METHODS: Experimental detachments were created in cats, rabbits, and ground squirrels and the retinas harvested 1, 3, 7, or 28 days later. Retinal reattachments of 28 days in duration were also performed in cats following a 3-day detachment. Human tissue was obtained during reattachment surgery. Microglia and macrophages were labeled with the lectins Griffonia simplicifolia and Ricinus communis and the antibody CD11b. M{\"u}ller cell and photoreceptor responses were followed immunocytochemically on the same tissue sections labeled with microglial markers. Images were collected by laser scanning confocal microscopy. RESULTS: Lightly labeled microglia were observed primarily in the inner retina of control tissue. In the cat and rabbit, a progressive increase in the number of labeled cells occurred in the outer retina beginning at 1 day of detachment. In both long term human and cat detachments numbers of microglia were elevated throughout the retina. This is in contrast to the rabbit and ground squirrel retinas where microglial activation was dramatically diminished in longer term detachments. Presumptive macrophages (anti-CD11b labeled cells) occurred only in the subretinal space. Retinal reattachment in cats significantly attenuated the response except in areas of poor outer segment regeneration. CONCLUSIONS: The robust microglial response to retinal detachment is an indicator of the importance of this cell type in the overall response of the retina. Our data suggest that the feline retina is a particularly appropriate model system for understanding this response in humans. Inhibiting the microglial response in that species should help us understand more precisely its potential role in photoreceptor survival in human pathology.}, Author = {Lewis, Geoffrey P. and Sethi, Charanjit S. and Carter, Katrina M. and Charteris, David G. and Fisher, Steven K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {1090-0535}, Journal = {Mol Vis}, Keywords = {11 Glia}, Month = {7}, Nlm_Id = {9605351}, Organization = {Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, CA.}, Pages = {491-500}, Pii = {v11/a57}, Pubmed = {16052164}, Title = {Microglial cell activation following retinal detachment: a comparison between species}, Uuid = {E569CAA8-956E-4981-8D8A-7FD5BB4714D1}, Volume = {11}, Year = {2005}} @article{Letang:1998, Abstract = {Previous work found that transplants of embryonic (E) day 16 occipital cortex placed into the frontal cortex of newborn hosts failed to receive input from visual-related nuclei of the host thalamus. The present study is aimed at determining the possible causes of the lack of visual-related thalamic input to these transplants. For that purpose, a retrograde neurotracer was injected into transplants of embryonic (E16) occipital origin which were placed into the frontal cortex of newborn rats with either intact or damaged occipital cortex. In rats with intact occipital cortex, occipital-to-frontal transplants were indeed not contacted by axons from the dorsal lateral geniculate (DLG) nucleus and received only sparse to negligible input from, respectively, the lateral posterior (LP) and laterodorsal (LD) thalamic nuclei. Yet, following neonatal lesion of the host occipital cortex, the occipital-to-frontal transplants received a significant input from the LP and to a much lesser degree from the LD but practically none from the DLG. Additional control cases with frontal-to-frontal transplants and prior lesion of the occipital cortex did not receive significant input from any of these thalamic nuclei. Thus, following neonatal deprivation of cortical target cells in their main terminal field, LP and to a lesser extent LD axons have the capacity to recognize and significantly innervate appropriate targets even those at some distance from their normal terminal site. DLG neurons degenerate or are not able to contact and invade available terminal space that is provided at some distance from the occipital cortex.}, Author = {L{\'e}tang, J. and Gaillard, A. and Roger, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Pregnancy;Animals;Frontal Lobe;Thalamic Nuclei;Brain Tissue Transplantation;Rats;Neural Pathways;Neocortex;Female;Axons;Rats, Wistar;Fetal Tissue Transplantation;Animals, Newborn;Cell Transplantation;Occipital Lobe;Immunohistochemistry;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {98348419}, Month = {7}, Nlm_Id = {0370712}, Number = {1}, Organization = {D{\'e}partement des Neurosciences, Laboratoire de Neurophysiologie, Universit{\'e} de Poitiers, 40 Av. du Recteur Pineau, Poitiers Cedex, 86022, France.}, Pages = {64-73}, Pii = {S0014488698968303}, Pubmed = {9682013}, Title = {Specific invasion of occipital-to-frontal neocortical grafts by axons from the lateral posterior thalamic nucleus consecutive to neonatal lesion of the rat occipital cortex}, Uuid = {C86C2EB4-4C4A-4898-8496-8470A1367A04}, Volume = {152}, Year = {1998}} @article{Levesque:1996a, Abstract = {Corticostriatal and corticothalamic projections arising from the second somatosensory area in the rat were studied after labeling small pools of neurons in laminae V and VI with biocytin. Tracing the axon of single neurons revealed the following principles of organization: (i) all corticostriatal and corticothalamic projections arising from layer V cells are collaterals of long-range corticofugal axons that also project below the thalamic level; (ii) all layer V cells that project to the thalamus also project to the striatum; (iii) all layer VI corticothalamic cells project exclusively to the thalamus; (iv) cells of the upper part of lamina VI send collaterals to the thalamic reticular nucleus and arborize in the ventrobasal complex forming rod-like terminal fields; and (v) cells of the lower part of lamina VI also send collaterals to the thalamic reticular nucleus, give off few branches in the ventrobasal complex and terminate principally in the caudal part of the posterior thalamic group. On the basis of these findings, and in the light of previous anatomical studies, it is proposed that the above mentioned organizing principles represent general rules that also apply to corticostriatal and corticothalamic pathways arising from other areas of the neocortex.}, Author = {L{\'e}vesque, M. and Gagnon, S. and Parent, A. and Desch\^{e}nes}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Neostriatum;24 Pubmed search results 2008;research support, non-u.s. gov't;Rats, Sprague-Dawley;21 Neurophysiology;Iontophoresis;Female;Pyramidal Cells;Neural Pathways;Rats;Lysine;Somatosensory Cortex;Animals;Male;Cerebral Cortex;Thalamus;Axons}, Nlm_Id = {9110718}, Number = {6}, Organization = {Centre de Recherche en Neurobiologie, H\^{o}pital de l'Enfant-J{\'e}sus, Qu{\'e}bec City, Canada.}, Pages = {759-70}, Pubmed = {8922332}, Title = {Axonal arborizations of corticostriatal and corticothalamic fibers arising from the second somatosensory area in the rat}, Uuid = {B44A81C8-178D-4D1C-B02C-1141ACD73AD9}, Volume = {6}, Year = {1996}, url = {papers/Lévesque_CerebCortex1996.pdf}} @article{Li:1995, Abstract = {In situ presence of numerous DNA strand breaks is a typical feature of apoptotic cells. Selective DNA strand break induction by photolysis (SBIP) at sites that contain incorporated halogenated DNA precursors has recently been proposed as a method of analysing DNA replication. Detection of DNA strand breaks, thus, enables one to identify apoptotic and/or DNA replicating cells. The current methods for DNA strand break labelling rely on the use of exogenous terminal deoxynucleotidyl transferase which either directly attaches the fluorochrome conjugated triphosphodeoxynucleotides to 3'OH ends in the breaks, or indirectly labels 3'OH ends with digoxygenin or biotin conjugated triphosphodeoxynucleotides. A limitation of these methodologies, especially restricting their routine application in the clinic, is high cost of reagents. In the present study we have tested whether relatively simple compound BrdUTP, which is approximately three orders of magnitude less expensive than dUTP conjugated to digoxygenin, can be used as marker of DNA strand breaks. Apoptosis of HL-60 cells was induced by DNA topoisomerase I inhibitor camptothecin. The incorporated BrdUTP was detected by fluoresceinated anti-BrdUrd MoAb. Cellular fluorescence was measured by flow cytometry as well as by Laser Scanning Cytometer (LSC). The data show that intensity of DNA strand break labelling with BrdUTP was nearly four- and two-fold higher than that obtained with the indirect labelling using biotin- or digoxygenin-conjugated dUTP, respectively, and over eight-fold higher than in the case of direct labelling with the fluorochrome (fluorescein or BODIPY)-conjugated deoxynucleotides. The increased labelling of DNA strand breaks with BrdUTP may reflect more efficient incorporation of this precursor by terminal transferase, compared to the nucleotides with bulky fluorochrome conjugates. DNA strand break labelling with BrdUTP, thus, offers a possibility of more sensitive (and at lower cost) detection of apoptotic or DNA replicating cells, compared to the alternative methods of DNA strand break labelling.}, Author = {Li, X. and Darzynkiewicz, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0960-7722}, Journal = {Cell Prolif}, Keywords = {23 dNTPs-Brdu;Fluorescent Dyes;Humans;DNA Topoisomerases, Type I;Cell Cycle;Sensitivity and Specificity;Apoptosis;23 Technique;Boron Compounds;Fluorescein-5-isothiocyanate;Research Support, U.S. Gov't, P.H.S.;Camptothecin;DNA Damage;Cell Division;Deoxyuracil Nucleotides;Biological Markers;HL-60 Cells;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {96150267}, Month = {11}, Nlm_Id = {9105195}, Number = {11}, Organization = {Cancer Research Institute, New York Medical College, Valhalla 10523, USA.}, Pages = {571-9}, Pubmed = {8555370}, Title = {Labelling DNA strand breaks with BrdUTP. Detection of apoptosis and cell proliferation}, Uuid = {A4A6DE04-1683-41AD-BE98-3E978C95CBB3}, Volume = {28}, Year = {1995}} @article{Li:2000, Abstract = {Bone morphogenetic proteins (BMPs) trigger neuronal differentiation of neocortical precursors within the ventricular zone (VZ) [Li et al. (1998): J Neurosci 18:8853-8862]. BMP-2/4 protein is concentrated at the VZ surface and BMPs rapidly promote the differentiation of neocortical precursors in both dissociated cell and explant cultures. Noggin binds to BMP-2/4 with high affinity, and prevents binding to cell surface receptors. In the present study, we used human recombinant noggin protein to determine whether endogenous BMP-2/4 triggers neuronal differentiation in dissociated cell culture. We find that noggin inhibits the differentiation of neocortical neurons: noggin decreases the number of MAP-2- and TUJ1-positive cells after 24 h of treatment, yet has no effect on either proliferation or cell survival. Noggin also significantly decreases neurite growth of MAP-2-positive cells. In addition, using Western blot analysis we show that noggin protein is present in developing cortex at E15. These results are consistent with previous results showing that endogenous BMPs trigger neuronal differentiation in the neocortical VZ and also indicate that a balance of noggin and BMP may regulate the differentiation of neocortical neurons in vivo.}, Author = {Li, W. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Neurons;Proteins;Embryo;10 Development;Research Support, Non-U.S. Gov't;Carrier Proteins;Embryonic and Fetal Development;Cell Differentiation;Research Support, U.S. Gov't, P.H.S.;Neocortex;Cell Survival;Cell Division;Humans;Mice;Animals;Microtubule-Associated Proteins;Cells, Cultured}, Medline = {20125901}, Nlm_Id = {7809375}, Number = {1-2}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, Conn., USA.}, Pages = {68-73}, Pii = {dne22068}, Pubmed = {10657699}, Title = {Noggin is a negative regulator of neuronal differentiation in developing neocortex}, Uuid = {A4081506-385B-4EB3-B94A-DBA1C59ED151}, Volume = {22}, Year = {2000}, url = {papers/Li_DevNeurosci2000.pdf}} @article{Li:2005, Abstract = {The dentate gyrus is one of two locations with continuing neurogenesis in adult mammals. While the function of adult neurogenesis is unknown, it is believed that it is involved in learning and memory. For adult neurogenesis to occur, the dentate gyrus must maintain the appropriate precursor cell niche in the subgranular zone, which is likely to be dependent on the developmental mechanisms at play in forming the dentate gyrus. In this review, we graft a molecular framework onto the known neuroanatomic developmental plan by considering the phenotypes of several mouse mutants that have well characterized dentate gyrus developmental abnormalities. This effort reveals that there are at least six distinct developmental steps that need to occur in the formation of the dentate gyrus, which can be associated with specific gene defects: (1) defining the dentate neuroepithelium; (2) forming the primary radial glial scaffolding; (3) radial migration of granule neurons to form the primordial granule cell layer; (4) establishing the precursor pool in the hilus; (5) radial transformation of the tertiary matrix, and (6) differentiation of dentate granule cells. From this analysis, it is clear that some molecular pathways control multiple steps in the development of the dentate gyrus. For example the Wnt pathway (steps 1, 2, 4) and the chemokine receptor CXCR4 (steps 3, 4) are involved in multiple developmental steps, while the neuronal differentiation gene NeuroD (step 6) and the integrin signaling pathway (step 5) are involved only in discrete stages of the dentate gyrus morphogenesis.}, Author = {Li, Guangnan and Pleasure, Samuel J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Nlm_Id = {7809375}, Number = {2-4}, Organization = {Department of Neurology, Programs in Neuroscience, Developmental Biology and Epilepsy Research, University of California, San Francisco, CA 94143, USA.}, Pages = {93-9}, Pii = {DNE20050272_4093}, Pubmed = {16046842}, Title = {Morphogenesis of the dentate gyrus: what we are learning from mouse mutants}, Uuid = {4AFD26A8-667B-11DA-A4B6-000D9346EC2A}, Volume = {27}, Year = {2005}, url = {papers/Li_DevNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000085980}} @article{Li:2001, Abstract = {Early after infection, the retroviral RNA genome is reverse transcribed to generate a linear cDNA copy, then that copy is integrated into a chromosome of the host cell. We report that unintegrated viral cDNA is a substrate for the host cell non-homologous DNA end joining (NHEJ) pathway, which normally repairs cellular double-strand breaks by end ligation. NHEJ activity was found to be required for an end-ligation reaction that circularizes a portion of the unintegrated viral cDNA in infected cells. Consistent with this, the NHEJ proteins Ku70 and Ku80 were found to be bound to purified retroviral replication intermediates. Cells defective in NHEJ are known to undergo apoptosis in response to retroviral infection, a response that we show requires reverse transcription to form the cDNA genome but not subsequent integration. We propose that the double-strand ends present in unintegrated cDNA promote apoptosis, as is known to be the case for chromosomal double-strand breaks, and cDNA circularization removes the pro-apoptotic signal.}, Author = {Li, L. and Olvera, J. M. and Yoder, K. E. and Mitchell, R. S. and Butler, S. L. and Lieber, M. and Martin, S. L. and Bushman, F. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0261-4189}, Journal = {EMBO J}, Keywords = {Research Support, Non-U.S. Gov't;Hamsters;Animals;HIV-1;DNA-Binding Proteins;Humans;Cell Line, Transformed;Research Support, U.S. Gov't, Non-P.H.S.;Apoptosis;CHO Cells;15 Retrovirus mechanism;DNA Helicases;Research Support, U.S. Gov't, P.H.S.;Moloney murine leukemia virus;Saccharomyces cerevisiae Proteins;3T3 Cells;Antigens, Nuclear;Mice;Virus Integration;24 Pubmed search results 2008;DNA, Viral;Nuclear Proteins;Terminal Repeat Sequences;Transcription, Genetic}, Medline = {21299385}, Month = {6}, Nlm_Id = {8208664}, Number = {12}, Organization = {Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.}, Pages = {3272-81}, Pubmed = {11406603}, Title = {Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection}, Uuid = {08F87F4C-FC74-49A2-992F-EBBBFDCDF8E7}, Volume = {20}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/emboj/20.12.3272}} @article{Li:2003, Abstract = {Radial glia are a polarized cell type that in most neural regions appear only transiently during development. They have long been recognized as glia or glial progenitors that support neuronal migration. Recent evidence indicates that radial glia also give rise to neurons and appear to be a major population of dividing precursor cells in the embryonic cortical ventricular zone. Radial glia extend long processes from the ventricular zone to the pial surface that provide guides for neuronal migration. We reasoned that the unique morphology of radial glia is due to the composition and organization of their cytoskeleton. In this present study, we have used C6-R, a radial glial-like cell line and isolated perinatal cerebellar radial glia to ask what are the critical cytoskeletal elements in radial glial cells and how they are regulated. Treatments with nocodazole and cytochalasin D showed that microtubules, but not microfilaments, are critical for the polarized morphology of radial glia. In addition, quantitative real-time PCR indicated that certain mRNAs specific for microtubule-associated proteins (MAPs) are selectively expressed in radial glia. These results together with the known ability of microtubule affinity-regulating kinases to regulate microtubule organization suggest that microtubules and MAPs are critical for the morphology of radial glia. 0894-1491 Journal Article}, Author = {Li, H. and Berlin, Y. and Hart, R. P. and Grumet, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Glia}, Keywords = {Brain/growth &development/metabolism/ultrastructure;Animals;Cells, Cultured;Cell Polarity/drug effects/physiology;Rats;Protein-Serine-Threonine Kinases/*genetics;Nocodazole/pharmacology;Microtubules/drug effects/metabolism/*ultrastructure;Stem Cells/metabolism/ultrastructure;Cell Differentiation/drug effects/*physiology;Rats, Sprague-Dawley;08 Aberrant cell cycle;Cytochalasin D/pharmacology;Support, Non-U.S. Gov't;Animals, Newborn;RNA, Messenger/drug effects/metabolism;Support, U.S. Gov't, P.H.S.;Microtubule-Associated Proteins/*genetics;Cell Size/drug effects/physiology;Neuroglia/metabolism/*ultrastructure;EE, G abstr}, Number = {1}, Organization = {Department of Cell Biology and Neuroscience and WM Keck Center for Collaborative Neuroscience, Rutgers, State University of New Jersey, Piscataway, New Jersey 08854, USA.}, Pages = {37-46}, Title = {Microtubules are critical for radial glial morphology: possible regulation by MAPs and MARKs}, Uuid = {31D292BF-5993-4694-81BE-AD113B17CDA7}, Volume = {44}, Year = {2003}, url = {papers/Li_Glia2003.pdf}} @article{Li:1999, Abstract = {Small, circumscribed electrolytic lesions were made in the upper cervical corticospinal tract in adult rats. In the centre of the lesion, the axons and all other tissue elements were totally destroyed. Surrounding this region of destruction is an area of tissue which is only partially damaged. In this area TUNEL positive staining of contiguous rows of tract glial cells indicates massive oligodendrocytic apoptosis at 1-3 days after operation, but axons, astrocytes and blood vessels survive. From around 4 days, the corticospinal axons in this area are demyelinated, and the microglia contain ingested myelin, identified in electron micrographs as characteristic MBP immunoreactive laminar cytoplasmic bodies. After around 3 weeks, large numbers of Schwann cells, continuous with those on the pial surface of the spinal cord, accumulate along the lesion track and selectively infiltrate the perilesional reactive area, where they mingle intimately with the phagocytic microglia. Electron micrographs show that at this time basal lamina-enclosed Schwann cell processes establish non-myelinated ensheathment of axons. From around 4 weeks after operation, prominent Schwann cell myelination is indicated by P0 immunoreactivity, and peripheral type, one-to-one myelination in electron micrographs. Thus the effect of the selective loss of oligodendrocytes is to first activate microglia, and then to induce a replacement of myelin by Schwann cells.}, Author = {Li, Y. and Field, P. M. and Raisman, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Phagocytosis;Animals;Myelin Sheath;Rats;Myelin Basic Proteins;Apoptosis;Female;Microglia;Oligodendroglia;Rats, Inbred Strains;Cell Movement;Not relevant;11 Glia;Pyramidal Tracts;Axons;Spinal Cord Injuries;Schwann Cells;Support, Non-U.S. Gov't;In Situ Nick-End Labeling;Microscopy, Electron;Demyelinating Diseases}, Medline = {20204293}, Nlm_Id = {0364620}, Number = {4-5}, Organization = {Norman and Sadie Lee Research Centre, Division of Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.}, Pages = {417-27}, Pubmed = {10739580}, Title = {Death of oligodendrocytes and microglial phagocytosis of myelin precede immigration of Schwann cells into the spinal cord}, Uuid = {37748B49-5705-4F35-9DD1-1B07C2A58F96}, Volume = {28}, Year = {1999}} @article{Li:2002a, Abstract = {We tested the hypothesis that populations of ependymal, subependymal and choroid plexus cells proliferate and differentiate after stroke in adult rats. Rats were subjected to 2 h of middle cerebral artery occlusion (n=70) and euthanized at 1, 2, 4, 7, 14, 21 and 28 days (10 per time point). Hematoxylin and eosin staining and immunostaining were performed using antibodies against bromodeoxyuridine, neuronal nuclear antigen and glial fibrillary acidic protein after stroke. In normal nonischemic rats (n=10), single layers of ependymal and choroid plexus cells do not react with bromodeoxyuridine, neuronal nuclear antigen or glial fibrillary acidic protein. Individual subependymal cells express glial fibrillary acidic protein and bromodeoxyuridine, but not neuronal nuclear antigen. After stroke, increased bromodeoxyuridine reactivity was present in multiple layers of ependymal cells and nodules of subependymal cells and in scattered choroid plexus cells from 2 to 28 days and peaked at 7 days. Bromodeoxyuridine immunoreactivity colocalized with neural phenotypes of neuronal nuclear antigen (~0.1- 3.5\%) and glial fibrillary acidic protein (~8.6\%) immunoreactivity in cells in the ventricular zone and the subventricular zone, as well as in the choroid plexus of the ischemia affected hemisphere. Our data suggest that ependymal, subependymal and choroid plexus cells are potential neural precursor cells in the adult mammalian brain.}, Author = {Li, Y. and Chen, J. and Chopp, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurol Sci}, Keywords = {D abstr;06 Adult neurogenesis injury induced}, Number = {2}, Organization = {Department of Neurology, Henry Ford Health Sciences Center, 2799 West Grand Boulevard, 48202, Detroit, MI, USA}, Pages = {137-46.}, Title = {Cell proliferation and differentiation from ependymal, subependymal and choroid plexus cells in response to stroke in rats}, Uuid = {5652C4EE-D17E-42D8-A2FD-DF6CBF7B3330}, Volume = {193}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11790394}} @article{Li:2002b, Abstract = {Many applications of hematopoietic gene therapy require selection for clones with active transgene expression. However, it was unclear whether the clonal progeny of a retrovirally transduced hematopoietic stem cell would be capable of maintaining transgene expression through serial repopulation and multilineage differentiation. Such investigations require simultaneous analyses of clonality, multilineage activity and transgene copy numbers. Using a mouse model, the present study demonstrates that a single hematopoietic stem cell expressing a marker gene from one or two insertions of a simple retroviral vector actively maintains multilineage transgene expression in the vast majority (80-99\%) of bone marrow and peripheral blood cells. Gene expression persisted through serial transplantations for at least 97 weeks post gene transfer and was observed in the lymphoid (B, T and NK cells), myeloid (CD11b(+), Gr-1(+)), erythroid (Ter119(+), mature red blood cells) and megakaryocytic (as indicated by platelets) progeny. Therefore, a single immunoselection for hematopoietic stem cells expressing the transgene in vivo was sufficient to establish a completely chimeric hematopoiesis. These observations imply that the retroviral vectors used in this study contain cis-elements that mediate expression through massive clonal expansion and multilineage differentiation, provided the insertion occurred in genetic loci permissive for expression in hematopoietic stem cells.}, Author = {Li, Z. and Fehse, B. and Schiedlmeier, B. and D{\"u}llmann, J. and Frank, O. and Zander, A. R. and Ostertag, W. and Baum, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0887-6924}, Journal = {Leukemia}, Keywords = {Transgenes;Transduction, Genetic;Gene Dosage;Colony-Forming Units Assay;Humans;Chimera;Transfection;Animals;Female;Mice, Transgenic;Antigens, CD34;Retroviridae;Mice, Inbred C57BL;11 Glia;Hematopoietic Stem Cell Transplantation;Green Fluorescent Proteins;Hematopoiesis;Bone Marrow Cells;Gene Transfer Techniques;Cell Lineage;Gene Silencing;Mice;Hematopoietic Stem Cells;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22188889}, Month = {9}, Nlm_Id = {8704895}, Number = {9}, Organization = {Experimental Cell Therapy, Department of Hematology and Oncology, Hannover Medical School, Hannover, Germany.}, Pages = {1655-63}, Pubmed = {12200677}, Title = {Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell}, Uuid = {108C22C6-2FC3-4384-9E52-478532C6FD66}, Volume = {16}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.leu.2402619}} @article{Li:2002, Abstract = {The developmental programme of embryogenesis is controlled by both genetic and epigenetic mechanisms. An emerging theme from recent studies is that the regulation of higher-order chromatin structures by DNA methylation and histone modification is crucial for genome reprogramming during early embryogenesis and gametogenesis, and for tissue-specific gene expression and global gene silencing. Disruptions to chromatin modification can lead to the dysregulation of developmental processes, such as X-chromosome inactivation and genomic imprinting, and to various diseases. Understanding the process of epigenetic reprogramming in development is important for studies of cloning and the clinical application of stem-cell therapy.}, Author = {Li, En}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1471-0056}, Journal = {Nat Rev Genet}, Keywords = {DNA Methylation;24 Pubmed search results 2008;Ectoderm;Embryonic and Fetal Development;Research Support, U.S. Gov't, P.H.S.;X Chromosome;Mammals;Trophoblasts;Models, Genetic;Chromatin;Humans;Animals;Germ Cells;review}, Medline = {22199595}, Month = {9}, Nlm_Id = {100962779}, Number = {9}, Organization = {Cardiovascular Research Center, Massachusetts General Hospital, Department of Medicine, Harvard Medical School, 149 13th Street, Charlestown, Massachusetts 02129, USA. en\@cvrc.mgh.harvard.edu}, Pages = {662-73}, Pii = {nrg887}, Pubmed = {12209141}, Title = {Chromatin modification and epigenetic reprogramming in mammalian development}, Uuid = {C7C10AC4-D242-4144-88E6-3F99798AE719}, Volume = {3}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrg887}} @article{Li:2007, Abstract = {The neuron-specific K-Cl cotransporter, KCC2, induces a developmental shift to render GABAergic transmission from depolarizing to hyperpolarizing. Now we demonstrate that KCC2, independently of its Cl(-) transport function, is a key factor in the maturation of dendritic spines. This morphogenic role of KCC2 in the development of excitatory synapses is mediated by structural interactions between KCC2 and the spine cytoskeleton. Here, the binding of KCC2 C-terminal domain to the cytoskeleton-associated protein 4.1N may play an important role. A more general conclusion based on our data is that KCC2 acts as a synchronizing factor in the functional development of glutamatergic and GABAergic synapses in cortical neurons and networks.}, Author = {Li, Hong and Khirug, Stanislav and Cai, Chunlin and Ludwig, Anastasia and Blaesse, Peter and Kolikova, Julia and Afzalov, Ramil and Coleman, Sarah K. and Lauri, Sari and Airaksinen, Matti S. and Kein{\"a}nen, Kari and Khiroug, Leonard and Saarma, Mart and Kaila, Kai and Rivera, Claudio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Institute of Biotechnology, University of Helsinki, Viikinkaari 4, FIN-00014, Helsinki, Finland.}, Pages = {1019-33}, Pii = {S0896-6273(07)00865-3}, Pubmed = {18093524}, Title = {KCC2 Interacts with the Dendritic Cytoskeleton to Promote Spine Development}, Uuid = {FC15E4C7-9342-4F76-B553-D7B124DBB7CC}, Volume = {56}, Year = {2007}, url = {papers/Li_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.10.039}} @article{Li:2002c, Abstract = {It is now apparent that adult neurogenesis is taking place during life in the olfactory bulb (OB) of the rodent brain. In the olfactory nervous system, the precursor cells of the subventricular zone are known to continually proliferate, migrate through the rostral migratory stream (RMS) and differentiate into the bulbar neurons. The RMS, consisting of heterogeneous cell populations of the neural and neuronal precursor cells, is the unique forebrain structure that provides a long-distance migratory route for the precursor cells. The present study was undertaken to examine whether neuronal regeneration, focusing on calretinin-immunoreactive (+) cells, may proceed in the RMS following lesions induced by an excitotoxin. Two days after ibotenate injections, massive degeneration of calretinin (+) cells occurred in the RMS and its adjacent forebrains. Thereafter, calretinin (+) cells gradually increased in the RMS and reached above their control value 2 weeks after ibotenate injections. Removal of the OB also produced a marked increase in calretinin (+) cells in the RMS. Autoradiographic experiments using (3)H-thymidine showed that calretinin (+) cells were continually generated in the RMS and underwent neuronal turnover within 8 weeks in a normal condition. The results indicate that, in terms of calretinin (+) cells, neuronal differentiation and replacement is continually taking place within the RMS, and that the RMS is capable of repopulating those cells which were injured by ibotenate. 0168-0102 Journal Article}, Author = {Li, Z. and Kato, T. and Kawagishi, K. and Fukushima, N. and Yokouchi, K. and Moriizumi, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Neurosci Res}, Keywords = {I both;Excitatory Amino Acid Agonists/toxicity;Calcium-Binding Protein, Vitamin D-Dependent/*analysis;Neurons/chemistry/*cytology/physiology;13 Olfactory bulb anatomy;Cell Count/statistics &numerical data;Immunohistochemistry;Rats;Rats, Wistar;Cell Movement/*physiology;Support, Non-U.S. Gov't;Animals;Male;Prosencephalon/chemistry/*cytology/drug effects/*physiology;Ibotenic Acid/*toxicity}, Number = {2}, Organization = {Department of Anatomy, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.}, Pages = {123-32}, Title = {Cell dynamics of calretinin-immunoreactive neurons in the rostral migratory stream after ibotenate-induced lesions in the forebrain}, Uuid = {1671C3B9-E979-44BE-8B58-4E7958710F21}, Volume = {42}, Year = {2002}, url = {papers/Li_NeurosciRes2002}} @article{Li:2003a, Abstract = {Cells undergoing apoptosis during development are removed by phagocytes, but the underlying mechanisms of this process are not fully understood. Phagocytes lacking the phosphatidylserine receptor (PSR) were defective in removing apoptotic cells. Consequently, in PSR-deficient mice, dead cells accumulated in the lung and brain, causing abnormal development and leading to neonatal lethality. A fraction of PSR knockout mice manifested a hyperplasic brain phenotype resembling that of mice deficient in the cell death-associated genes encoding Apaf-1, caspase-3, and caspase-9, which suggests that phagocytes may also be involved in promoting apoptosis. These data demonstrate a critical role for PSR in early stages of mammalian organogenesis and suggest that this receptor may be involved in respiratory distress syndromes and congenital brain malformations. 1095-9203 Journal Article}, Author = {Li, M. O. and Sarkisian, M. R. and Mehal, W. Z. and Rakic, P. and Flavell, R. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Science}, Keywords = {Receptors, Cell Surface/genetics/*metabolism;Cell Nucleus/ultrastructure;Pulmonary Surfactants/metabolism;10 Development;Animals;Brain/abnormalities/cytology/*embryology;Phagocytosis;In Situ Nick-End Labeling;Neurons/cytology;Phenotype;Phosphatidylserines/metabolism;Cell Division;11 Glia;Hematopoietic Stem Cell Transplantation;Support, U.S. Gov't, P.H.S.;Necrosis;Respiratory Insufficiency/etiology;Epithelial Cells/physiology/ultrastructure;F pdf;Eye Abnormalities/etiology;Lung/cytology/*embryology/physiology;Eye/embryology;Mesoderm/ultrastructure;Mice, Knockout;Macrophages/*physiology;Support, Non-U.S. Gov't;Mice;Inflammation;Reverse Transcriptase Polymerase Chain Reaction;*Apoptosis}, Number = {5650}, Organization = {Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA.}, Pages = {1560-3}, Pubmed = {14645847}, Title = {Phosphatidylserine receptor is required for clearance of apoptotic cells}, Uuid = {E539FCB2-EE25-11DA-8605-000D9346EC2A}, Volume = {302}, Year = {2003}, url = {papers/Li_Science2003.pdf}} @article{Lian:2006, Abstract = {PURPOSE OF REVIEW: The development of the cerebral cortex progresses through defined stages including neural proliferation, neuroblast migration and neuronal differentiation. Disruptions in each of these developmental stages can lead to characteristic cerebral cortical malformations. This review provides an overview of the known genetic causes of human cerebral developmental disorders and discusses the potential molecular mechanisms that contribute to these malformations. RECENT FINDINGS: Mutations in genes that are involved in neural proliferation give rise to microcephaly (small brain). Mutations in genes that direct the onset of neuroblast migration give rise to periventricular heterotopia (clusters of neurons along the ventricles of the brain). Mutations in genes that are required for neuroblast migration cause type I lissencephaly (smooth brain) and subcortical band heterotopia (smooth brain with a band of neurons beneath the cortex). Mutations in genes that direct migratory neurons to arrest in the cortex lead to type II lissencephaly (smooth brain with clusters of neurons along the surface of the brain). SUMMARY: The identification of causative genes involved in the formation of the cerebral cortex now allows for a rational approach with which to interpret the underlying mechanistic basis for many of these disorders.}, Author = {Lian, Gewei and Sheen, Volney}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1040-8703}, Journal = {Curr Opin Pediatr}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9000850}, Number = {6}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {614-20}, Pii = {00008480-200612000-00005}, Pubmed = {17099359}, Title = {Cerebral developmental disorders}, Uuid = {B677D117-C5F1-4408-BF7F-BF686220D42C}, Volume = {18}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1097/MOP.0b013e328010542d}} @article{Liang:2002, Abstract = {Human T-lymphotropic virus type 1 (HTLV-1) Tax exerts pleiotropic effects on multiple cellular regulatory processes to bring about NF-kappaB activation, aberrant cell cycle progression, and cell transformation. Here we report that Tax stimulates cellular G(1)/S entry but blocks mitosis. Tax expression in naive cells transduced with a retroviral vector, pBabe-Tax, leads to a significant increase in the number of cells in the S phase, with an accompanying rise in the population of cells with a DNA content of 4N or more. In all cell types tested, including BHK-21, mouse NIH 3T3, and human diploid fibroblast WI-38, Tax causes an uncoupling of DNA synthesis from cell division, resulting in the formation of multinucleated giant cells and cells with decondensed, highly convoluted and lobulated nuclei that are reminiscent of the large lymphocytes with cleaved or cerebriform nuclei seen in HTLV-1-positive individuals. This contrasts with the Tax-transformed cell lines, PX1 (fibroblast) and MT4 (lymphocyte), which produce Tax at high levels, but without the accompanying late-stage cell cycle abnormalities. PX1 and MT4 may have been selected to harbor somatic mutations that allow a bypass of the Tax-induced block in mitosis. 0022-538x Journal Article}, Author = {Liang, M. H. and Geisbert, T. and Yao, Y. and Hinrichs, S. H. and Giam, C. Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {J Virol}, Keywords = {Hamsters;Human;Transduction, Genetic;Animals;*Mitosis/drug effects;Cell Line, Transformed;Moloney murine leukemia virus/genetics;EE pdf;*S Phase/drug effects;Giant Cells;08 Aberrant cell cycle;Genetic Vectors;Cell Line;3T3 Cells;Support, U.S. Gov't, P.H.S.;Mice;Gene Products, tax/genetics/metabolism/pharmacology/*physiology;Cell Division/drug effects}, Number = {8}, Organization = {Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814, USA.}, Pages = {4022-33}, Title = {Human T-lymphotropic virus type 1 oncoprotein tax promotes S-phase entry but blocks mitosis}, Uuid = {D9FA1D40-F8F8-4C43-9C3D-4661B80F4500}, Volume = {76}, Year = {2002}, url = {papers/Liang_JVirol2002.pdf}} @article{Libri:1998, Abstract = {The effects of the selective GABA(B) receptor antagonist [3-[[(3,4-dichlorophenyl)methyl]aminolpropyl] (diethoxymethyl) phosphinic acid (CGP 52432) on muscarinic (mAChR) and metabotropic glutamate (mGluR) responsiveness were studied in slices of piriform cortex from both immature (P16-P22) and adult (> or =P40) rats, using a conventional intracellular recording technique. In both adult and immature slices, CGP 52432 (1 microM) had no effect on neuronal membrane properties, whereas it selectively abolished the late inhibitory postsynaptic potential (IPSP) evoked by local electrical stimulation of association fibre terminals. Age-related changes in mAChR (but not mGluR) responsiveness were also detected. In adult neurones, bath-application of the mAChR agonist oxotremorine-M (OXO-M; 10 microM), or the selective mGluR agonist 1S,3R-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD; 10 microM) evoked similar membrane depolarization and inhibition of evoked excitatory postsynaptic potentials (EPSPs). However, while 1S,3R-ACPD and OXO-M produced indistinguishable slow excitatory effects in immature slices, during superfusion with OXO-M, neurones exhibited spontaneous paroxysmal depolarizing shifts (PDSs) that were suppressed in the presence of atropine (1 microM) or the selective GABA(B) receptor agonist beta-parachlorophenyl-gamma-aminobutyric acid [(-)baclofen; 10 microM]. Also, application of OXO-M resulted in a pronounced prolongation (rather than a decrease) of electrically evoked postsynaptic potentials (PSPs) which now exhibited recurrent superimposed spike discharges. In adult slices, in the continuous presence of CGP 52432 (1 microM; 20 min pre-incubation), a subsequent exposure to 10 microM OXO-M or 1S,3R-ACPD failed to induce any spontaneous epileptiform activity, and evoked PSPs were consistently suppressed. In contrast, in immature slices, after incubation in CGP 52432 (1 microM; 20 min), a subsequent application of a low dose of OXO-M (2.5 microM), which was inactive per se, was able to produce spontaneous PDSs and a prolongation of evoked PSPs. We conclude that a reduction in GABA(B)-mediated synaptic inhibition in immature slices (in co-operation with other factors) may contribute to the facilitation of excitatory neurotransmission and therefore play a role in the generation of mAChR-induced epileptiform activity.}, Author = {Libri, V. and Constanti, A. and Postlethwaite, M. and Bowery, N. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0028-1298}, Journal = {Naunyn Schmiedebergs Arch Pharmacol}, Keywords = {Research Support, Non-U.S. Gov't;Dose-Response Relationship, Drug;Electric Stimulation;Animals;Oxotremorine;Rats;Muscarinic Agonists;Synaptic Transmission;Neuroprotective Agents;Cycloleucine;Epilepsy;Female;21 Epilepsy;Rats, Wistar;Receptors, Muscarinic;Receptors, GABA-B;Male;Cerebral Cortex;21 Neurophysiology;Phosphinic Acids;Neurons;Membrane Potentials;GABA Antagonists;24 Pubmed search results 2008;Receptors, Metabotropic Glutamate;Benzylamines;Excitatory Postsynaptic Potentials}, Medline = {98420449}, Month = {8}, Nlm_Id = {0326264}, Number = {2}, Organization = {Department of Pharmacology, The School of Pharmacy, University of London, UK.}, Pages = {168-74}, Pubmed = {9750001}, Title = {Blockade of GABA(B) receptors facilitates muscarinic agonist-induced epileptiform activity in immature rat piriform cortex in vitro}, Uuid = {19BC0118-BD86-470D-898B-5DEABCC11617}, Volume = {358}, Year = {1998}} @article{Lie:2004, Abstract = {New cells are continuously generated from immature proliferating cells throughout adulthood in many organs, thereby contributing to the integrity of the tissue under physiological conditions and to repair following injury. In contrast, repair mechanisms in the adult central nervous system (CNS) have long been thought to be very limited. However, recent findings have clearly demonstrated that in restricted areas of the mammalian brain, new functional neurons are constantly generated from neural stem cells throughout life. Moreover, stem cells with the potential to give rise to new neurons reside in many different regions of the adult CNS. These findings raise the possibility that endogenous neural stem cells can be mobilized to replace dying neurons in neurodegenerative diseases. Indeed, recent reports have provided evidence that, in some injury models, limited neuronal replacement occurs in the CNS. Here, we summarize our current understanding of the mechanisms controlling adult neurogenesis and discuss their implications for the development of new strategies for the treatment of neurodegenerative diseases. 0362-1642 Journal article}, Author = {Lie, D. C. and Song, H. and Colamarino, S. A. and Ming, G. L. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {Annu Rev Pharmacol Toxicol}, Keywords = {01 Adult neurogenesis general;A pdf}, Organization = {1Laboratory of Genetics, The Salk Institute, La Jolla, California 92037; email: lie\@salk.edu, colamarino\@salk.edu, gage\@salk.edu, 2Institute for Cell Engineering, Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; email: shongju1\@jhmi.edu, gming1\@jhmi.edu}, Pages = {399-421}, Title = {NEUROGENESIS IN THE ADULT BRAIN: New Strategies for Central Nervous System Diseases}, Uuid = {6E7AC1A9-0F63-4775-ABB8-6BC7F0B1314D}, Volume = {44}, Year = {2004}, url = {../../Volumes/Vega/Users/ackman/James/Endnotelibraries/OMEGAData/0561468416nnurev.pharmtox04.pdf}} @article{Lieber:1973, Author = {Lieber, M. M. and Todaro, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0020-7136}, Journal = {Int J Cancer}, Keywords = {15 ERVs retroelements;Clone Cells;Chromosomes;RNA-Directed DNA Polymerase;Cell Transformation, Neoplastic;Moloney murine leukemia virus;Microscopy, Electron;Cell Line;Retroviridae;Epitopes;Radioimmunoassay;15 Retrovirus mechanism;Animals;Bromodeoxyuridine;Mice;Cells, Cultured;24 Pubmed search results 2008}, Medline = {74173544}, Month = {5}, Nlm_Id = {0042124}, Number = {3}, Pages = {616-27}, Pubmed = {4133949}, Title = {Spontaneous and induced production of endogenous type-C RNA virus from a clonal line of spontaneously transformed BALB-3T3}, Uuid = {8DFFA5E0-4328-11DB-A5D2-000D9346EC2A}, Volume = {11}, Year = {1973}} @article{Lieber:2000, Abstract = {Moloney murine leukemia virus (MoMLV)-derived vectors require cell division for efficient transduction, which may be related to an inability of the viral DNA-protein complex to cross the nuclear membrane. In contrast, adenoviruses (Ad) can efficiently infect nondividing cells. This property may be due to the presence of multiple nuclear translocation signals in a number of Ad proteins, which are associated with the incoming viral genomes. Of particular interest is the Ad preterminal protein (pTP), which binds alone or in complex with the Ad polymerase to specific sequences in the Ad inverted terminal repeat. The goal of this study was to test whether coexpression of pTP with retroviral DNA carrying pTP-binding sites would facilitate nuclear import of the viral preintegration complex and transduction of quiescent cells. In preliminary experiments, we demonstrated that the karyophylic pTP can coimport plasmid DNA into the nuclei of growth-arrested cells. Retroviral transduction studies were performed with G(1)/S-arrested LTA cells or stationary-phase human primary fibroblasts. These studies demonstrated that pTP or pTP-Ad polymerase conferred nuclear import of retroviral DNA upon arrested cells when the retrovirus vector contained the corresponding binding motifs. However, pTP-mediated nuclear translocation of MoMLV DNA in nondividing cells was not sufficient for stable transduction. Additional cellular factors activated during S phase or DNA repair synthesis were required for efficient retroviral integration. 0022-538x Journal Article}, Author = {Lieber, A. and Kay, M. A. and Li, Z. Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Journal = {J Virol}, Keywords = {Human;Protein Precursors/genetics/*metabolism;Animals;Viral Proteins/genetics/*metabolism;Cells, Cultured;Transfection;Biological Transport;Cell Line, Transformed;*Virus Integration;J pdf;15 Retrovirus mechanism;Cell Nucleus/metabolism/virology;Moloney murine leukemia virus/*genetics;Adenoviruses, Human/*physiology;Plasmids;Support, Non-U.S. Gov't;DNA, Viral/*metabolism;Phosphoproteins/genetics/*metabolism;Support, U.S. Gov't, P.H.S.;Mice;Cell Division}, Number = {2}, Organization = {Division of Medical Genetics, University of Washington, Seattle, Washington 98195, USA. lieber00\@u.washington.edu}, Pages = {721-34}, Pubmed = {10623734}, Title = {Nuclear import of moloney murine leukemia virus DNA mediated by adenovirus preterminal protein is not sufficient for efficient retroviral transduction in nondividing cells}, Uuid = {15111441-1DD3-4845-9F8A-CC80289AB0E1}, Volume = {74}, Year = {2000}, url = {papers/Lieber_JVirol2000.pdf}} @article{Lieber:1973a, Author = {Lieber, M. M. and Livingston, D. M. and Todaro, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {15 ERVs retroelements;Clone Cells;RNA-Directed DNA Polymerase;Cell Transformation, Neoplastic;Kinetics;Virus Replication;Retroviridae;Gammaretrovirus;15 Retrovirus mechanism;Mice;Bromodeoxyuridine;RNA Viruses;Animals;24 Pubmed search results 2008}, Medline = {73216982}, Month = {8}, Nlm_Id = {0404511}, Number = {98}, Pages = {443-4}, Pubmed = {4123998}, Title = {Superinduction of endogenous type C virus by 5-bromodeoxyuridine from transformed mouse clones}, Uuid = {8DFFAE50-4328-11DB-A5D2-000D9346EC2A}, Volume = {181}, Year = {1973}} @article{Lieberam:2005, Abstract = {Motor neurons, alone among neurons in the vertebrate CNS, extend axons out of the neural tube to innervate peripheral targets. Two classes of motor neurons, termed vMNs and dMNs, extend axons out of the neural tube via ventral and dorsal exit points, respectively, in accord with their homeodomain transcription factor repertoire. Downstream of these transcriptional codes, the cell surface receptors that shape initial motor axon trajectories have not been identified. We show here that the chemokine receptor Cxcr4 is expressed on the axons of vMNs as they follow their ventral trajectory, whereas its ligand, Cxcl12, is expressed by mesenchymal cells surrounding the ventral neural tube. Genetic studies reveal that Cxcl12-Cxcr4 signaling directs the ventral trajectory of spinal vMNs. In its absence, these neurons adopt a dMN-like trajectory, despite preservation of their vMN transcriptional identity. Thus, the status of Cxcr4 signaling helps to determine the initial axonal trajectory of mammalian motor neurons.}, Author = {Lieberam, Ivo and Agalliu, Dritan and Nagasawa, Takashi and Ericson, Johan and Jessell, Thomas M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;11 Glia}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, New York, New York 10032.}, Pages = {667-79}, Pii = {S0896-6273(05)00653-7}, Pubmed = {16129397}, Title = {A cxcl12-CXCR4 chemokine signaling pathway defines the initial trajectory of Mammalian motor axons}, Uuid = {375DF883-064B-42A8-9044-0CB5938C6451}, Volume = {47}, Year = {2005}, url = {papers/Lieberam_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.08.011}} @article{Lieberman:2005, Abstract = {Evolutionary dynamics have been traditionally studied in the context of homogeneous or spatially extended populations. Here we generalize population structure by arranging individuals on a graph. Each vertex represents an individual. The weighted edges denote reproductive rates which govern how often individuals place offspring into adjacent vertices. The homogeneous population, described by the Moran process, is the special case of a fully connected graph with evenly weighted edges. Spatial structures are described by graphs where vertices are connected with their nearest neighbours. We also explore evolution on random and scale-free networks. We determine the fixation probability of mutants, and characterize those graphs for which fixation behaviour is identical to that of a homogeneous population. Furthermore, some graphs act as suppressors and others as amplifiers of selection. It is even possible to find graphs that guarantee the fixation of any advantageous mutant. We also study frequency-dependent selection and show that the outcome of evolutionary games can depend entirely on the structure of the underlying graph. Evolutionary graph theory has many fascinating applications ranging from ecology to multi-cellular organization and economics.}, Author = {Lieberman, Erez and Hauert, Christoph and Nowak, Martin A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Models, Biological;20 Networks;Mutation;Probability;research support, non-u.s. gov't;Population Dynamics;Selection (Genetics);Stochastic Processes;09 Evolutionary dynamics;Ecology;research support, u.s. gov't, non-p.h.s.;Evolution;Genetic Drift;Reproduction;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0410462}, Number = {7023}, Organization = {Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA. erez\@erez.com}, Pages = {312-6}, Pii = {nature03204}, Pubmed = {15662424}, Title = {Evolutionary dynamics on graphs}, Uuid = {7646A438-8A95-459C-8AB4-2D139273B751}, Volume = {433}, Year = {2005}, url = {papers/Lieberman_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03204}} @article{Lien:2006, Abstract = {During development, cells monitor and adjust their rates of accumulation to produce organs of predetermined size. We show here that central nervous system-specific deletion of the essential adherens junction gene, alphaE-catenin, causes abnormal activation of the hedgehog pathway, resulting in shortening of the cell cycle, decreased apoptosis, and cortical hyperplasia. We propose that alphaE-catenin connects cell-density-dependent adherens junctions with the developmental hedgehog pathway and that this connection may provide a negative feedback loop controlling the size of developing cerebral cortex.}, Author = {Lien, Wen-Hui H. and Klezovitch, Olga and Fernandez, Tania E. and Delrow, Jeff and Vasioukhin, Valeri}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Cell Differentiation;Signal Transduction;Animals;Trans-Activators;Up-Regulation;Oligonucleotide Array Sequence Analysis;Cell Cycle;Mitosis;Apoptosis;Models, Biological;Mutation;Cell Count;Cell Polarity;Cell Adhesion;Cerebral Cortex;Neurons;alpha Catenin;Hyperplasia;Mice;24 Pubmed search results 2008;Central Nervous System;Stem Cells;Adherens Junctions;Research Support, N.I.H., Extramural}, Month = {3}, Nlm_Id = {0404511}, Number = {5767}, Organization = {Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.}, Pages = {1609-12}, Pii = {311/5767/1609}, Pubmed = {16543460}, Title = {alphaE-catenin controls cerebral cortical size by regulating the hedgehog signaling pathway}, Uuid = {2F3A68C8-2D04-4BBF-A9A8-D3F587816FED}, Volume = {311}, Year = {2006}, url = {papers/Lien_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1121449}} @article{Lim:2008, Abstract = {Ephrin-Eph signaling is involved in axon guidance during development, but it may also regulate synapse development after the axon has contacted the target cell. Here we report that the activation of ephrin-B reverse signaling in the developing Xenopus laevis optic tectum promotes morphological and functional maturation of retinotectal synapses. Elevation of ephrin-B signaling increased the number of retinotectal synapses and stabilized the axon arbors of retinal ganglion cells. It also enhanced basal synaptic transmission and activity-induced long-term potentiation (LTP) of retinotectal synapses. The functional effects were caused by a rapid enhancement of presynaptic glutamate release and a delayed increase in the postsynaptic glutamate responsiveness. The facilitated LTP induction occurred during the early phase of enhanced transmitter release and appeared to be causally related to the late-phase postsynaptic maturation via an NMDA receptor-dependent mechanism. This ephrin-B-dependent synapse maturation supports the notion that the ephrin/Eph protein families have multiple functions in neural development.}, Author = {Lim, Byung Kook and Matsuda, Naoto and Poo, Mu-Ming M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {10 Development;10 circuit formation;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9809671}, Number = {2}, Organization = {Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, University of California, Berkeley, California 94720-3200, USA.}, Pages = {160-9}, Pii = {nn2033}, Pubmed = {18193042}, Title = {Ephrin-B reverse signaling promotes structural and functional synaptic maturation in vivo}, Uuid = {CCA7A8E1-3CF0-4285-9A7B-19B5E97686E3}, Volume = {11}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn2033}} @article{Lim:2000, Abstract = {Large numbers of new neurons are born continuously in the adult subventricular zone (SVZ). The molecular niche of SVZ stem cells is poorly understood. Here, we show that the bone morphogenetic protein (BMP) antagonist Noggin is expressed by ependymal cells adjacent to the SVZ. SVZ cells were found to express BMPs as well as their cognate receptors. BMPs potently inhibited neurogenesis both in vitro and in vivo. BMP signaling cell-autonomously blocked the production of neurons by SVZ precursors by directing glial differentiation. Purified mouse Noggin protein promoted neurogenesis in vitro and inhibited glial cell differentiation. Ectopic Noggin promoted neuronal differentiation of SVZ cells grafted to the striatum. We thus propose that ependymal Noggin production creates a neurogenic environment in the adjacent SVZ by blocking endogenous BMP signaling.}, Author = {Lim, D. A. and Tramontin, A. D. and Trevejo, J. M. and Herrera, D. G. and Garcia-Verdugo, J. M. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Neuron}, Keywords = {Cell Differentiation/drug effects;Human;Cell Survival/drug effects;inhibitors/biosynthesis/pharmacology;Brain Tissue Transplantation;Mice, Mutant Strains;Microinjections;Animal;Mice, Transgenic;Corpus Striatum/cytology/metabolism;Bone Morphogenetic Proteins/*antagonists &;Fetal Tissue Transplantation;Cell Line;C-17;Ependyma/cytology/metabolism;Receptors, Cell Surface/biosynthesis;Neurons/cytology/*metabolism/transplantation;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Mice;Signal Transduction/drug effects/*physiology;Gene Expression;Cell Division/drug effects;Proteins/*metabolism/pharmacology}, Number = {3}, Organization = {Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.}, Pages = {713-26.}, Title = {Noggin antagonizes BMP signaling to create a niche for adult neurogenesis}, Uuid = {2A223AF6-9A16-4590-860F-22A046B261CF}, Volume = {28}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11163261}} @article{Lim:1997, Abstract = {The mammalian subventricular zone (SVZ) of the lateral wall of the forebrain ventricle retains a population of proliferating neuronal precursors throughout life. Neuronal precursors born in the postnatal and adult SVZ migrate to the olfactory bulb where they differentiate into interneurons. Here we tested the potential of mouse postnatal SVZ precursors in the environment of the embryonic brain: (i) a ubiquitous genetic marker, (ii) a neuron-specific transgene, and (iii) a lipophilic-dye were used to follow the fate of postnatal day 5-10 SVZ cells grafted into embryonic mouse brain ventricles at day 15 of gestation. Graft-derived cells were found at multiple levels of the neuraxis, including septum, thalamus, hypothalamus, and in large numbers in the midbrain inferior colliculus. We observed no integration into the cortex. Neuronal differentiation of graft derived cells was demonstrated by double-staining with neuron-specific beta-tubulin antibodies, expression of the neuron-specific transgene, and the dendritic arbors revealed by the lipophilic dye. We conclude that postnatal SVZ cells can migrate through and differentiate into neurons within multiple embryonic brain regions other than the olfactory bulb. 1st report of broad differentiation&migration potential of postnatalSVZ precursors transplant into embryonic brain}, Author = {Lim, D. A. and Fishell, G. J. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {*Cell Movement;02 Adult neurogenesis migration;Cell Differentiation;03 Adult neurogenesis progenitor source;Biological Markers;Animal;Neurons/*cytology/transplantation;Cerebral Ventricles/*cytology/*embryology;Support, U.S. Gov't, P.H.S.;Mice;BB abstr}, Number = {26}, Organization = {The Rockefeller University, New York, NY 10021, USA.}, Pages = {14832-6.}, Title = {Postnatal mouse subventricular zone neuronal precursors can migrate and differentiate within multiple levels of the developing neuraxis}, Uuid = {89C9DA53-4DF3-4504-B90A-7FDA777E62F9}, Volume = {94}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9405699}} @article{Lim:1999, Abstract = {Neurogenesis continues in the mammalian subventricular zone (SVZ) throughout life. However, the signaling and cell-cell interactions required for adult SVZ neurogenesis are not known. In vivo, migratory neuroblasts (type A cells) and putative precursors (type C cells) are in intimate contact with astrocytes (type B cells). Type B cells also contact each other. We reconstituted SVZ cell-cell interactions in a culture system free of serum or exogenous growth factors. Culturing dissociated postnatal or adult SVZ cells on astrocyte monolayers-but not other substrates-supported extensive neurogenesis similar to that observed in vivo. SVZ precursors proliferated rapidly on astrocytes to form colonies containing up to 100 type A neuroblasts. By fractionating the SVZ cell dissociates with differential adhesion to immobilized polylysine, we show that neuronal colony-forming precursors were concentrated in a fraction enriched for type B and C cells. Pure type A cells could migrate in chains but did not give rise to neuronal colonies. Because astrocyte-conditioned medium alone was not sufficient to support SVZ neurogenesis, direct cell-cell contact between astrocytes and SVZ neuronal precursors may be necessary for the production of type A cells.}, Author = {Lim, D. A. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:52 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {B-16 both;02 Adult neurogenesis migration;Prosencephalon/*cytology/physiology;Adult;Human;Neurons/*cytology/physiology;Astrocytes/*cytology/physiology;Cell Differentiation/physiology;Support, U.S. Gov't, P.H.S.;Cells, Cultured;Cell Communication/*physiology;Cell Movement/physiology}, Number = {13}, Organization = {The Rockefeller University, New York, NY 10021, USA. limd\@rockvax.rockefeller.edu}, Pages = {7526-31.}, Title = {Interaction between astrocytes and adult subventricular zone precursors stimulates neurogenesis}, Uuid = {513EE85C-FBD9-46D3-B47A-8F5736240ECE}, Volume = {96}, Year = {1999}, url = {papers/Lim_ProcNatlAcadSciUSA1999.pdf}} @article{Lima:2005, Abstract = {Optically gated ion channels were expressed in circumscribed groups of neurons in the Drosophila CNS so that broad illumination of flies evoked action potentials only in genetically designated target cells. Flies harboring the "phototriggers" in different sets of neurons responded to laser light with behaviors specific to the sites of phototrigger expression. Photostimulation of neurons in the giant fiber system elicited the characteristic escape behaviors of jumping, wing beating, and flight; photostimulation of dopaminergic neurons caused changes in locomotor activity and locomotor patterns. These responses reflected the direct optical activation of central neuronal targets rather than confounding visual input, as they persisted unabated in carriers of a mutation that eliminates phototransduction. Encodable phototriggers provide noninvasive control interfaces for studying the connectivity and dynamics of neural circuits, for assigning behavioral content to neurons and their activity patterns, and, potentially, for restoring information corrupted by injury or disease.}, Author = {Lima, Susana Q. and Miesenb{\"o}ck, Gero}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Lasers;Motor Activity;Electrophysiology;Photic Stimulation;Cells, Cultured;Animals;Cloning, Molecular;Larva;Phototransduction;23 Technique;Ion Channels;Male;Research Support, U.S. Gov't, P.H.S.;Action Potentials;Neurons;Drosophila;24 Pubmed search results 2008;Central Nervous System;Ion Channel Gating;Receptors, Purinergic P2;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {0413066}, Number = {1}, Organization = {Department of Cell Biology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06520, USA.}, Pages = {141-52}, Pii = {S0092-8674(05)00115-7}, Pubmed = {15820685}, Title = {Remote control of behavior through genetically targeted photostimulation of neurons}, Uuid = {57E32EEE-8576-4851-BA0F-3D282A1520E4}, Volume = {121}, Year = {2005}, url = {papers/Lima_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.02.004}} @article{Lin:2006, Abstract = {Neural stem and progenitor cells typically exhibit a density-dependent survival and expansion, such that critical densities are required below which clonogenic progenitors are lost. This suggests that short-range autocrine factors may be critical for progenitor cell maintenance. We report here that purines drive the expansion of ventricular zone neural stem and progenitor cells, and that purine receptor activation is required for progenitor cells to be maintained as such. Neural progenitors expressed P2Y purinergic receptors and mobilized intracellular calcium in response to agonist. Receptor antagonists suppressed proliferation and permitted differentiation into neurons and glia in vitro, while subsequent removal of purinergic inhibition restored progenitor cell expansion. Real-time bioluminescence imaging of extracellular ATP revealed that the source of extracellular nucleotides are the progenitor cells themselves, which appear to release ATP in episodic burst events. Enzyme histochemistry of the adult rat brain for ectonucleotidase activity revealed that NTDPase, which acts to degrade active ATP and thereby clears it from areas of active purinergic transmission, was selectively localized to the subventricular zone and the dentate gyrus, regions in which neuronal differentiation proceeds from the progenitor cell pool. These data suggest that purine nucleotides act as proliferation signals for neural progenitor cells, and thereby serve as negative regulators of terminal neuronal differentiation. As a result, progenitor cell-derived neurogenesis is thus associated with regions of both active purinergic signaling and modulation thereof.}, Author = {Lin, and Takano, and Arcuino, and Wang, and Hu, and Darzynkiewicz, and Nunes, and Goldman, and Nedergaard,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {0372762}, Organization = {Department of Cell Biology, New York Medical College, Valhalla, NY, USA.}, Pii = {S0012-1606(06)01218-8}, Pubmed = {17188262}, Title = {Purinergic signaling regulates neural progenitor cell expansion and neurogenesis}, Uuid = {5E3043F7-34AB-4E8C-9CC0-DFB260A67CE3}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2006.09.017}} @article{Lin:2002, Abstract = {Antibodies against the chondroitin sulfate proteoglycan NG2 label a subpopulation of glial cells within the CNS, which have a small cell body and thin radiating processes. Physiological recordings from these small cells in acute brain slices have revealed that they possess unique properties, suggesting that they may comprise a class of glial cells distinct from astrocytes, oligodendrocytes, or microglia. NG2-expressing glial cells (abbreviated as "NG2 cells"here) have a moderate input resistance and are not dye- or tracer-coupled to adjacent cells. They express voltage-gated Na+, K+ and Ca2+ conductances, though they do not exhibit regenerative Na+ or Ca2+ action potentials due to the much larger K+ conductances present. In addition to voltage-gated conductances, they express receptors for various neurotransmitters. In the hippocampus, AMPA and GABAA receptors on these cells are activated by release of transmitter from neurons at defined synaptic junctions that are formed with CA3 pyramidal neurons and GABAergic interneurons. These rapid forms of neuron-glial communication may regulate the proliferation rate of NG2 cells or their development into mature oligodendrocytes. These depolarizing inputs may also trigger the release of neuroactive substances from NG2 cells, providing feedback regulation of signaling at neuronal synapses. Although the presence of Ca2+ permeable AMPA receptors provides a pathway to link neuronal activity to Ca2+ dependent processes within the NG2 cells, these receptors also put these cells at risk for glutamate-associated excitotoxicity. This vulnerability to the sustained elevation of glutamate may underlie ischemic induced damage to white matter tracts and contribute to cerebral palsy in premature infants. 0300-4864 Journal Article}, Author = {Lin, S. C. and Bergles, D. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurocytol}, Keywords = {11 Glia;G pdf}, Number = {6-7}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe St., WBSB 813, Baltimore, MD 21205, USA.}, Pages = {537-49}, Pubmed = {14501222}, Title = {Physiological characteristics of NG2-expressing glial cells}, Uuid = {90E9978F-E2A4-4DA7-859A-144C5D9B0F26}, Volume = {31}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14501222}} @article{Lin:2005, Abstract = {Mammalian urine releases complex mixtures of volatile compounds that are used in reproduction, territoriality and conspecific recognition. To understand how such complex mixtures are represented in the main olfactory bulb, we analysed the electrophysiological responses of individual mitral cells to volatile compounds in mouse urine. In both males and females, urine volatile compounds evoke robust responses in a small subset of mitral cells. Fractionation of the volatile compounds using gas chromatography showed that out of the hundreds of compounds present, mitral cells are activated by single compounds. One cohort of mitral cells responded exclusively to male urine; these neurons were activated by (methylthio)methanethiol, a potent, previously unknown semiochemical present only in male urine. When added to urine, synthetic (methylthio)methanethiol significantly enhances urine attractiveness to female mice. We conclude that mitral cells represent natural odorant stimuli by acting as selective feature detectors, and that their activation is largely independent of the presence of other components in the olfactory stimulus.}, Author = {Lin, and Zhang, and Block, and Katz,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:26 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0410462}, Organization = {HHMI and Department of Neurobiology, Box 3209, Duke University Medical Center, Durham, North Carolina 27710, USA.}, Pii = {nature03414}, Pubmed = {15724148}, Title = {Encoding social signals in the mouse main olfactory bulb}, Uuid = {78BE30DA-BC2F-4899-B2BE-C551B3DF9413}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03414}} @article{Lin:1976, Abstract = {Using a membrane filter assay, we have obtained results from both kinetic and competition experiments indicating that histones bind more strongly to bromodeoxyuridine-substituted DNA than to normal DNA. At 37 degrees C in our standard buffer of 0.2 M ionic strength, the rate of dissociation of histones H1, H2, and h4 from BrdU-substituted DNA is respectively 7, 4, and 2 times slower than it is from normal DNA. Competition experiments show an even greater difference between BrdU-substituted and normal DNA with respect to histone binding. The tighter binding of histones to BrdU-substituted DNA is of interest because of the known effects of BrdU on eukaryotic chromosome condensation and staining, virus induction, and the inhibition of differentiation.}, Author = {Lin, S. and Lin, D. and Riggs, A. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:52 -0400}, Issn = {0305-1048}, Journal = {Nucleic Acids Res}, Keywords = {01 Adult neurogenesis general;Protein Binding;Binding Sites;Histones;Comparative Study;DNA;Osmolar Concentration;DNA, Viral;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Plants;Filtration;Bromodeoxyuridine;Hydrogen-Ion Concentration;23 Technique}, Medline = {77013012}, Month = {9}, Nlm_Id = {0411011}, Number = {9}, Pages = {2183-91}, Pubmed = {9622}, Title = {Histones bind more tightly to bromodeoxyuridine-substituted DNA than to normal DNA}, Uuid = {A280D993-F40F-49C1-9736-16114411117B}, Volume = {3}, Year = {1976}, url = {papers/Lin_NucleicAcidsRes1976.pdf}} @article{Lindner:2003, Abstract = {Recommendations from experts and recently established guidelines on how to improve the face and predictive validity of animal models of stroke have stressed the importance of using older animals and long-term behavioral-functional endpoints rather than relying almost exclusively on acute measures of infarct volume in young animals. The objective of the present study was to determine whether we could produce occlusions in older rats with an acceptable mortality rate and then detect reliable, long-lasting functional deficits. A reversible intraluminar suture middle cerebral artery occlusion (MCAO) procedure was used to produce small infarcts in middle-aged rats. This resulted in an acceptable mortality rate, and robust disabilities were detected in functional assays, although the degree of total tissue loss measured 90 d after MCAO was quite modest. Infarcted animals were functionally impaired relative to sham control animals even 90 d after the occlusions, and when animals were subgrouped based on amount of tissue loss, MCAO animals with only 4\%tissue loss exhibited enduring neurological-behavioral impairments relative to sham-operated controls, and the functional impairments in the group with the largest infarcts (20\%tissue loss) were more severe than the functional impairments in the rats with 4\%tissue loss. These results suggest that this model, using reversible MCAO to produce small infarcts and long-lasting functional-behavioral deficits in older rats, may represent an advance in the relatively higher-throughput modeling of stroke and its recovery in rodents and may be useful in the development and characterization of future stroke therapies. 1529-2401 Journal Article}, Author = {Lindner, M. D. and Gribkoff, V. K. and Donlan, N. A. and Jones, T. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurosci}, Keywords = {*Disease Models, Animal;Forelimb/physiopathology;Brain/blood supply/pathology;Rats;Predictive Value of Tests;Survival Rate;Infarction, Middle Cerebral Artery/*diagnosis/pathology/*physiopathology;*Severity of Illness Index;Reproducibility of Results;Motor Activity;11 Glia;Animals;Age Factors;G pdf;*Behavior, Animal}, Number = {34}, Organization = {Neuroscience Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA. Mark.Lindner\@BMS.com}, Pages = {10913-22}, Pubmed = {14645487}, Title = {Long-lasting functional disabilities in middle-aged rats with small cerebral infarcts}, Uuid = {8048D81D-7D4F-4E86-93AC-5D8526087394}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14645487}} @article{Lindner:1976, Abstract = {Explants and cells of nervous tissue were cultivated in the presence of aethanol, tween 80, dimethylformamid (DMF) and dimethylsulfoxid (DMSO) and the influence upon the index of area, the growth rate and fiber index was observed. They are important to solutions of drugs for tests in vitro. At the beginning of the cultivation aethanol in vitro influenced the regeneration of nerve fibers from explants and cells. A significant increase of the index of growth was observed. After a long term influence of tween 80, DMF and DMSO an inhibition of differentiation of neurons in vitro was observed. TY - JOUR M1 - 1088567 M2 - Uber die Wirkung von Athanol und anderen Losungsmitteln auf das Nervengewebe unter In-vitro-Bedingungen.}, Author = {Lindner, G. and Grosse, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Isbn = {0044-3107}, Journal = {Z Mikrosk Anat Forsch}, Keywords = {Dimethylformamide;English Abstract;Polysorbates;Tissue Culture;Cell Differentiation;Ethanol;Polyethylene Glycols;Rats;Animals;Comparative Study;Dimethyl Sulfoxide;Cell Count;Telencephalon;Hippocampus;08 Aberrant cell cycle;Trigeminal Ganglion;Chick Embryo;Neurons;Heart Ventricles;Cell Division;EE abstr;Culture Media}, Number = {3}, Pages = {557-564}, Title = {Action of ethanol and other solvents on the nerve tissue under in vitro conditions}, Uuid = {6ACD2CF9-43D6-4472-9772-232F0D7D9DA6}, Volume = {90}, Year = {1976}, Bdsk-Url-1 = {http://www.hubmed.org/display.cgi?issn=00443107&uids=1088567}} @article{Lindvall:2003, Abstract = {0027-8424 Comment Journal Article}, Author = {Lindvall, O. and McKay, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Dopamine/metabolism;Human;06 Adult neurogenesis injury induced;Brain/*metabolism/*physiology;D pdf;Neurons/metabolism;Animals;*Regeneration;Central Nervous System/physiology}, Number = {13}, Organization = {Wallenberg Neuroscience Center, Department of Clinical Neuroscience, University Hospital, Solvegatan 17 BMC A-11, 22184 Lund, Sweden.}, Pages = {7430-1}, Pubmed = {12810949}, Title = {Brain repair by cell replacement and regeneration}, Uuid = {E9FBAF76-84ED-46FF-A72C-8D0981C28B7E}, Volume = {100}, Year = {2003}, url = {papers/Lindvall_ProcNatlAcadSciUSA2003.pdf}} @article{Ling:1989, Abstract = {The present study describes neuronal degeneration and its accompanying non-neuronal cellular reaction in the hypoglossal nucleus following an intraneural injection of Ricinus communis agglutinin-60 (RCA-60) into the hypoglossal nerve. The first noticeable structural changes were observed in neurons in hamsters killed 3 days after the RCA injection. Drastic alterations occurred in the period extending from the 5th to the 15th postoperative day. Two forms of neuronal degeneration were observed: light and dark types. In the light type, masses of free ribosomes were observed; other changes included the dilation of Golgi saccules and the presence of abnormal mitochondria. In the dark type of degeneration, the cells became condensed with vacuoles in their cytoplasm. Axon terminals presynaptic to the degenerating cells during this period appeared to be normal. A massive influx of mononuclear leucocytes by diapedesis occurred at the large venules. Some of the infiltrated cells were clearly lymphocytes, while others were monocytes which became indistinguishable from indigenous microglia once they were in the neuropil. Neural macrophages, most probably derived both from microglia and the infiltrated monocytes, were engaged in the phagocytosis of neuronal debris. A remarkable finding in the present study was the wide-spread occurrence of dark axon terminals in the neuropil in longer surviving animals (90 and 120 days). The structural alterations, e.g., clumping and swelling of some of the synaptic vesicles in the enhanced cytoplasmic density, suggest that these were undergoing atrophic changes resulting from the long period of dysfunction following the death of postsynaptic neurons induced by RCA.}, Author = {Ling, E. A. and Shieh, J. Y. and Wen, C. Y. and Yick, T. Y. and Wong, W. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0914-9465}, Journal = {Arch Histol Cytol}, Keywords = {Hamsters;Neurons;Nerve Degeneration;Lectins;Not relevant;Plant Lectins;11 Glia;Mesocricetus;Injections;Hypoglossal Nerve;Support, Non-U.S. Gov't;Male;Animals}, Medline = {90105065}, Month = {10}, Nlm_Id = {8806082}, Number = {4}, Organization = {Department of Anatomy, Faculty of Medicine, National University of Singapore.}, Pages = {345-54}, Pubmed = {2513846}, Title = {Neural degeneration and non-neuronal cellular reactions in the hypoglossal nucleus following an intraneural injection of toxic ricin}, Uuid = {FA74EBF9-40A5-4B9A-9EEE-23E9DF588DEA}, Volume = {52}, Year = {1989}} @article{Ling:1997, Abstract = {Studies in songbirds suggest that neurogenesis during the first few years of life is related to song learning. In this study, we examined whether postnatal neurogenesis occurs in a nonsongbird, the ring dove (Streptoplia risoria), and whether it persists to old age. Twenty-four hours after a single intramuscular injection of [3H]thymidine, labeled cells were present in the brains, particularly in the lateral wall of the lateral ventricle of juvenile (3-month and 8-month) and adult (1- year to 8-year) doves. Two months after multiple [3H]thymidine injections, there were fewer labeled cells in the ventricular zone (VZ), but many labeled cells with neuronal morphology in the parenchyma of the forebrain; labeled cells were confirmed as neurons by using neuron-specific markers, microtubule-associated protein-2 (MAP-2) and anti-neuronal nucleus (NeuN). In general, new neurons were distributed in the forebrain without clustering in any particular nucleus. During the first year of life, however, neostriatum caudale and hyperstriatum, the regions known to be essential for proper integration of sensory cues and reproductive behavior, contained more new neurons than any other brain regions. These neuronal additions showed an age-related decline; the first reduction coincided with the dove's attainment of adult physical size (about 3 months old) and the second occurred when the dove would normally attain reproductive fitness (about 1 year old). A low level of forebrain neurogenesis persisted up to 8 years of age (the oldest animals studied). These observations suggest that neurogenesis in adulthood is widespread among birds but that the biological significance of adult neurogenesis in the ring dove remains to be determined.}, Author = {Ling, C. and Zuo, M. and Alvarez-Buylla, A. and Cheng, M. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Comp Neurol}, Keywords = {01 Adult neurogenesis general;Cell Division/physiology;Thymidine/diagnostic use;Comparative Study;Autoradiography;Female;A abstr;Cell Count;Neurons/*cytology;Tritium/diagnostic use;Support, U.S. Gov't, P.H.S.;Aging/*physiology;Animal;Male;Birds/*physiology;Telencephalon/cytology/*growth &development;Support, Non-U.S. Gov't}, Number = {2}, Organization = {Department of Brain &Cognitive Science, Massachusetts Institute of Technology, Cambridge 02139, USA.}, Pages = {300-12.}, Title = {Neurogenesis in juvenile and adult ring doves}, Uuid = {80D1A5B6-B2B1-4C10-B321-758E76214853}, Volume = {379}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9050792}} @article{Linnarsson:2000, Abstract = {There are two populations of neurons which are continually renewed in the adult, the dentate gyrus granule neurons and the olfactory bulb granule and periglomerular neurons. In the dentate gyrus, a secondary proliferative zone termed the subgranular zone is established along the interface between the dentate gyrus and the hilus where granule cells are born throughout life. Olfactory bulb neurons are generated in the anterior subventricular zone of the lateral ventricle and migrate via the rostral migratory stream to the olfactory bulb. We examined animals lacking brain-derived neurotrophic factor (BDNF) in order to establish whether this neurotrophin could be involved in the generation and/or survival of these neurons in vivo. We find that cells in nestin- positive regions of both the subgranular layer of the dentate gyrus and the subventricular zone of the olfactory bulb undergo apoptosis starting 2 weeks after birth in the absence of BDNF. However, increased apoptosis was not limited to precursors, as apoptotic cells were also found in the granule cell layer of the dentate gyrus and in the granule and periglomerular layers of the olfactory bulb. The excessive cell death was limited to these populations of neurons as no excessive cell death was detected in other forebrain areas. We conclude that BDNF is essential for the survival of neurons specifically in populations which are continuously being regenerated in the brain.}, Author = {Linnarsson, S. and Willson, C. A. and Ernfors, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Brain Res Mol Brain Res}, Keywords = {Aging;Olfactory Bulb/cytology/growth &development/*physiology;Mice, Knockout;Brain-Derived Neurotrophic Factor/deficiency/genetics/*physiology;C;Neurons/*cytology/physiology;Cerebral Ventricles/cytology/growth &development/*physiology;Nerve Regeneration/*physiology;Cell Survival;Animal;04 Adult neurogenesis factors;Support, Non-U.S. Gov't;Mice;Apoptosis/*physiology;Dentate Gyrus/cytology/growth &development/*physiology;In Situ Nick-End Labeling}, Number = {1}, Organization = {Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Doktorsringen 12A, 171 77, Stockholm, Sweden.}, Pages = {61-9.}, Title = {Cell death in regenerating populations of neurons in BDNF mutant mice}, Uuid = {323BCDD7-7AE6-4DBF-9C00-86AAF56C0520}, Volume = {75}, Year = {2000}, url = {papers/Linnarsson_BrainResMolBrainRes2000.pdf}} @article{Lipardi:2001, Abstract = {In posttranscriptional gene silencing (PTGS), "quelling,"and RNA interference (RNAi), 21-25 nucleotide RNA fragments are produced from the initiating dsRNA. These short interfering RNAs (siRNAs) mediate RNAi by an unknown mechanism. Here, we show that GFP and Pp-Luc siRNAs, isolated from a protein complex in Drosophila embryo extract, target mRNA degradation in vitro. Most importantly, these siRNAs, as well as a synthetic 21-nucleotide duplex GFP siRNA, serve as primers to transform the target mRNA into dsRNA. The nascent dsRNA is degraded to eliminate the incorporated target mRNA while generating new siRNAs in a cycle of dsRNA synthesis and degradation. Evidence is presented that mRNA-dependent siRNA incorporation to form dsRNA is carried out by an RNA-dependent RNA polymerase activity (RdRP). 0092-8674 Journal Article}, Author = {Lipardi, C. and Wei, Q. and Paterson, B. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Cell}, Keywords = {Drosophila/embryology;*RNA Processing, Post-Transcriptional;RNA, Untranslated/*biosynthesis/metabolism;RNA, Antisense;*Gene Silencing;RNA/*metabolism;Micrococcal Nuclease/metabolism;T abstr;RNA, Double-Stranded/*metabolism;RNA, Messenger/*metabolism;Animals;RNA, Small Interfering;Polymerase Chain Reaction;23 Technique;Luminescent Proteins/genetics/metabolism}, Number = {3}, Organization = {Laboratory of Biochemistry, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.}, Pages = {297-307}, Pubmed = {11701121}, Title = {RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs}, Uuid = {111B4059-78BB-44CE-9EED-DB1339EA65D8}, Volume = {107}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11701121}} @article{Lipscomb:2002, Abstract = {The murine olfactory system consists of two primary divisions: (1) a main olfactory system, in which olfactory sensory neurons (OSNs) located in the main olfactory epithelium (MOE) send their axons to glomeruli in the main olfactory bulb (MOB); and (2) an accessory olfactory system, in which OSNs located in the vomeronasal organ send their axons to glomeruli in the accessory olfactory bulb (AOB). In labeling studies using the lectin Ulex europaeus agglutinin (UEA), we discovered a novel subset of small neuropilar structures in the MOB that are distinct from other glomeruli both in the MOB and AOB. These "microglomeruli"are morphologically similar to MOB glomeruli in many respects: they receive innervation from processes present in the olfactory nerve layer and are isolated from other glomeruli by juxtaglomerular cells; in addition, the compartmental pattern of UEA labeling suggests the presence of UEA (-) processes within their neuropil. Microglomeruli contained processes that express the olfactory marker protein, a marker common to mature OSN axons. However, unlike other glomerular structures, the microglomeruli did not contain neural cell adhesion molecule-labeled processes. Within microglomeruli, UEA(+) processes interdigitated with MAP2(+) dendrites, some of which likely originate from interneurons, as indicated by glutamic acid decarboxylase labeling. Synaptophysin labeling in microglomeruli strongly suggested that synapses occur between UEA(+) processes and dendrites. Anterograde labeling of OSNs, by injection of rhodamine- dextran into one naris, demonstrated that UEA(+) processes in microglomeruli originated in the MOE. The unique morphology, protein expression, and location of microglomeruli have led us to hypothesize that they represent a novel class of glomerular structures in the murine olfactory system.}, Author = {Lipscomb, B. W. and Treloar, H. B. and Greer, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurosci}, Keywords = {I;13 Olfactory bulb anatomy}, Number = {3}, Organization = {Interdepartmental Neuroscience Graduate Program, Department of Neurosurgery, and Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.}, Pages = {766-74.}, Title = {Novel microglomerular structures in the olfactory bulb of mice}, Uuid = {85181C1D-59A3-40D8-BC27-46CCE1BBBB95}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11826106%20http://www.jneurosci.org/cgi/content/full/22/3/766%20http://www.jneurosci.org/cgi/content/abstract/22/3/766}} @article{Lipson:2007, Abstract = {The emergence of communication is considered one of the major transitions in evolution. Recent work using robot-based simulation shows that communication arises spontaneously. While deceptive communication arises in a purely competitive setting, cooperative communication arises only subject to group or kin selection.}, Author = {Lipson, Hod}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {20 Networks;Neural Networks (Computer);Selection (Genetics);09 Evolutionary dynamics;Cooperative Behavior;Evolution;comment;Competitive Behavior;Animals;Animal Communication;Robotics;review;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {9107782}, Number = {9}, Organization = {Mechanical & Aerospace Engineering, Cornell University, Ithaca, New York, USA. hl274\@cornell.edu}, Pages = {R330-2}, Pii = {S0960-9822(07)01070-6}, Pubmed = {17470348}, Title = {Evolutionary robotics: emergence of communication}, Uuid = {0EBCBCF1-F01E-4D3D-A6F7-4BAD98B325EE}, Volume = {17}, Year = {2007}, url = {papers/Lipson_CurrBiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2007.03.003}} @article{Liu:2005a, Abstract = {The plant innate immune response includes the hypersensitive response (HR), a form of programmed cell death (PCD). PCD must be restricted to infection sites to prevent the HR from playing a pathologic rather than protective role. Here we show that plant BECLIN 1, an ortholog of the yeast and mammalian autophagy gene ATG6/VPS30/beclin 1, functions to restrict HR PCD to infection sites. Initiation of HR PCD is normal in BECLIN 1-deficient plants, but remarkably, healthy uninfected tissue adjacent to HR lesions and leaves distal to the inoculated leaf undergo unrestricted PCD. In the HR PCD response, autophagy is induced in both pathogen-infected cells and distal uninfected cells; this is reduced in BECLIN 1-deficient plants. The restriction of HR PCD also requires orthologs of other autophagy-related genes including PI3K/VPS34, ATG3, and ATG7. Thus, the evolutionarily conserved autophagy pathway plays an essential role in plant innate immunity and negatively regulates PCD.}, Author = {Liu, Yule and Schiff, Michael and Czymmek, Kirk and Tall{\'o}czy, Zsolt and Levine, Beth and Dinesh-Kumar, S. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Molecular Sequence Data;Organelles;Base Sequence;Proteins;Gene Expression Regulation, Plant;Apoptosis;Research Support, U.S. Gov't, Non-P.H.S.;Plant Proteins;Tobacco;1-Phosphatidylinositol 3-Kinase;Research Support, U.S. Gov't, P.H.S.;Saccharomyces cerevisiae Proteins;Microscopy, Electron, Transmission;Tumor Suppressor Proteins;Amino Acid Sequence;Research Support, N.I.H., Extramural;Tobacco Mosaic Virus;24 Pubmed search results 2008;Immunity, Natural;Autophagocytosis}, Month = {5}, Nlm_Id = {0413066}, Number = {4}, Organization = {Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.}, Pages = {567-77}, Pii = {S0092-8674(05)00240-0}, Pubmed = {15907470}, Title = {Autophagy regulates programmed cell death during the plant innate immune response}, Uuid = {8AEA457A-F07E-4435-9E84-1B46663D9DEA}, Volume = {121}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.03.007}} @article{Liu:2003a, Abstract = {Seizures increase dentate granule cell proliferation in adult rats but decrease proliferation in young pups. The particular period and number of perinatal seizures required to cause newborn granule cell suppression in development are unknown. Therefore, we examined cell proliferation with bromodeoxyuridine (BrdU) immunohistochemistry during the peak of neurogenesis (e.g., P6 and P9) and at later postnatal ages (e.g., P13, P20, or P30) following single and multiple episodes of perinatal status epilepticus induced by kainate (KA). Because an inverse relationship exists between glucocorticosteroids (CORT) levels and granule cell proliferation, plasma CORT levels and electroencephalographic (EEG) activity were simultaneously monitored to elucidate underlying mechanisms that inhibit cell proliferation. In control animals, the number of BrdU-labeled cells increased then declined with maturation. After 1x KA or 2x KA administered on P6 and P9, the numbers of BrdU-labeled cells were not different from age-matched controls. However, rat pups with 3x KA (on P6, P9, and P13) had marked suppression of BrdU-labeled cells 48-72 h after the last seizure (43 +/- 6.5\%of control). Cell proliferation was also significantly inhibited on P20 after 2x KA (to 56 +/- 6.9\%) or 3x KA (to 54 +/- 7.9\%) and on P30 with 3x KA (to 74.5 +/- 8.2\%of age-matched controls). Cell death was not apparent as chromatin stains showed increased basophilia of only inner cells lining the granule cell layers, in the absence of eosinophilia, argyrophilia, or terminal deoxynucleotidyl dUTP nick endlabeling (TUNEL) labeling at times examined. In P13 pups with 3x KA, electron microscopy revealed an increased number of immature granule cells and putative stem cells with irregular shape, condensed cytoplasm, and electron dense nuclei, and they were also BrdU positive. The EEG showed no relationship between neurogenesis and duration of high-synchronous ictal activity. However, endocrine studies showed a correlation with BrdU number and age, sustained increases in circulating CORT levels following 1x KA on P6 (0.7 +/- 0.1 to 2.40 +/- 0.86 microg/dl), and cumulative increases that exceeded 10 microg/dl at 4-8 h after 3x KA on P13 or P20. In conclusion, a history of only one or two perinatal seizure(s) can suppress neurogenesis if a second or third seizure recurs after a critical developmental period associated with a marked surge in CORT. During the first 2 weeks of postnatal life sustained increases in postictal circulating CORT levels but not duration or intensity of ictal activity has long-term consequences on neurogenesis. The occurrence of an increased proportion of immature granule cells and putative stem cells with irregular morphology in the absence of neurodegeneration suggests that progenitors may not differentiate properly and remain in an immature state.}, Author = {Liu, H. and Kaur, J. and Dashtipour, K. and Kinyamu, R. and Ribak, C. E. and Friedman, L. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Fluorescent Antibody Technique, Indirect;Silver Staining;Animals;Rats;Seizures;Cell Count;Rats, Sprague-Dawley;Hippocampus;Cytoplasmic Granules;Antimetabolites;Status Epilepticus;Hydrocortisone;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;In Situ Nick-End Labeling;Glucocorticoids;Dentate Gyrus;Radioimmunoassay;24 Pubmed search results 2008;Immunohistochemistry;Microscopy, Electron;Bromodeoxyuridine;Electroencephalography}, Medline = {22999028}, Month = {11}, Nlm_Id = {0370712}, Number = {1}, Organization = {New Jersey Neuroscience Institute, Seton Hall University, South Orange, NJ 07079, USA.}, Pages = {196-213}, Pii = {S0014488603002073}, Pubmed = {14637092}, Title = {Suppression of hippocampal neurogenesis is associated with developmental stage, number of perinatal seizure episodes, and glucocorticosteroid level}, Uuid = {17AE3D08-D878-4CD9-AAD5-00DD2873DAF7}, Volume = {184}, Year = {2003}} @article{Liu:1998a, Abstract = {We have examined the glial cell response, the possible expression of compounds associated with the complement cascade, including the putative complement inhibitor clusterin, and their cellular association during Wallerian degeneration in the central nervous system. Examination of the proliferation pattern revealed an overall greater mitotic activity after rhizotomy, an exclusive involvement of microglia in this proliferation after peripheral nerve injury, but, in addition, a small fraction of proliferating astrocytes after rhizotomy. Immunostaining with the phagocytic cell marker ED1 gradually became very prominent after rhizotomy, possibly reflecting a response to the extensive nerve fiber disintegration. Lumbar dorsal rhizotomy did not induce endogenous immunoglobulin G (IgG) deposition or complement expression in the spinal cord dorsal horn, dorsal funiculus, or gracile nucleus. This is in marked contrast to the situation after peripheral nerve injury, which appears to activate the entire complement cascade in the vicinity of the central sensory processes. Clusterin, a multifunctional protein with complement inhibitory effects, was markedly upregulated in the dorsal funiculus in astrocytes. In addition, there was an intense induction of clusterin expression in the degenerating white matter in oligodendrocytes, possibly reflecting a degeneration process in these cells. The findings suggest that 1) complement expression by microglial cells is intimately associated with IgG deposition; 2) axotomized neuronal perikarya, but not degenerating central fibers, undergo changes which induce such deposition; and 3) clusterin is not related to complement expression following neuronal injury but participates in regulating the state of oligodendrocytes during Wallerian degeneration.}, Author = {Liu, L. and Persson, J. K. and Svensson, M. and Aldskogius, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Wallerian Degeneration;Brain Stem;Complement Inactivators;Complement;Sciatic Nerve;Organ Specificity;Oligodendroglia;Oligonucleotides, Antisense;Animals;Phagocytosis;Cell Division;RNA, Messenger;In Situ Hybridization;11 Glia;Molecular Chaperones;Biological Markers;Not relevant;Gene Expression Regulation;Comparative Study;Rats, Sprague-Dawley;Glial Fibrillary Acidic Protein;Neuroglia;Rats;Female;Complement Activation;Microglia;Spinal Nerve Roots;Glycoproteins;Rhizotomy;Immunoglobulin G;Support, Non-U.S. Gov't;Nerve Tissue Proteins;Astrocytes}, Medline = {98295564}, Month = {7}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Anatomy, Biomedical Center, Uppsala University, Sweden. li.liu\@anatomi.uu.se}, Pages = {221-38}, Pii = {10.1002/(SICI)1098-1136(199807)23:3<221::AID-GLIA5>3.0.CO;2-7}, Pubmed = {9633807}, Title = {Glial cell responses, complement, and clusterin in the central nervous system following dorsal root transection}, Uuid = {1677A3C6-CD3E-4603-AE33-5894A0ECB285}, Volume = {23}, Year = {1998}} @article{Liu:2003c, Abstract = {The olfactory bulb (OB) core is an extension of the rostral migratory stream and thus is a potential source of neural progenitor and neural stem cells. We characterized in vivo and in vitro neuronal progenitor and neural stem cells in the adult OB core. In mouse and rat, bromodeoxyuridine (BrdU) labeling showed that the OB core accumulates newly replicated cells. Nestin, a neuroepithelial stem cell marker, was enriched in the OB core. BrdU-positive cells were immunolabeled for nestin and TUC4, a marker for early postmitotic neurons. The distributions of cells labeled for BrdU, TUC4, and nestin were similarly concentrated in the OB core. Nestin- and TUC4-positive cells were also found in the OB of young and aged humans. Isolated and cultured OB core cells from adult rat and mouse had the capacity to generate numerous neurospheres. Adult OB core neurospheres were cryopreserved and subsequently cultured. Single cell clonal analysis of neurospheres revealed the capacity for self-renewal and multipotency. Cultured adult OB core cells differentiated into neurons, astrocytes, and oligodendrocytes. Some neurons expressed choline acetlytransferase, substance P, and glutamic acid decarboxylase. Basic fibroblast growth factor potentiated the self-renewal of cells and beta-nerve growth factor stimulated differentiation. OB-derived neural stem cells in coculture with skeletal muscle cells were induced to become neurons expressing choline acetyltransferase and substance P and formed neuromuscular synaptic junctions on myocytes displaying acetylcholinesterase-positive motor end plates. Cocultured OB-derived neural stem cells with myoblast cells also generated nonneural cell progeny. We conclude that the adult mammalian OB core is a reservoir of neural progenitor cells and pluripotent neural stem cells. 0021-9967 Journal Article}, Author = {Liu, Z. and Martin, L. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {J Comp Neurol}, Keywords = {Human;Animals;Neurons/chemistry/*cytology/drug effects;Cells, Cultured;Stem Cells/chemistry/*cytology/drug effects;Rats;Comparative Study;Cell Survival/drug effects/physiology;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Mice, Inbred C57BL;Male;Aged;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;BB pdf;Aged, 80 and over;Cell Differentiation/drug effects/physiology;Adult;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Mice;Olfactory Bulb/chemistry/*cytology/drug effects;Coculture/methods}, Number = {4}, Organization = {Department of Pathology, Division of Neuropathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, Pages = {368-91}, Title = {Olfactory bulb core is a rich source of neural progenitor and stem cells in adult rodent and human}, Uuid = {13289AF0-9881-4C21-8D64-D922E74D4A43}, Volume = {459}, Year = {2003}, url = {papers/Liu_JCompNeurol2003}} @article{Liu:1998, Abstract = {Neurogenesis in the dentate gyrus of adult rodents is regulated by NMDA receptors, adrenal steroids, environmental stimuli, and seizures. To determine whether ischemia affects neurogenesis, newly divided cells in the dentate gyrus were examined after transient global ischemia in adult gerbils. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) immunohistochemistry demonstrated a 12-fold increase in cell birth in the dentate subgranular zone 1-2 weeks after 10 min bilateral common carotid artery occlusions. Two minutes of ischemia did not significantly increase BrdU incorporation. Confocal microscopy demonstrated that BrdU immunoreactive cells in the granule cell layer colocalized with neuron-specific markers for neuronal nuclear antigen, microtubule-associated protein-2, and calbindin D28k, indicating that the newly divided cells migrated from the subgranular zone into the granule cell layer and matured into neurons. Newborn cells with a neuronal phenotype were first seen 26 d after ischemia, survived for at least 7 months, were located only in the granule cell layer, and comprised approximately 60\%of BrdU-labeled cells in the granule cell layer 6 weeks after ischemia. The increased neurogenesis was not attributable to entorhinal cortical lesions, because no cell loss was detected in this region. Ischemic preconditioning for 2 min, which protects CA1 neurons against subsequent ischemic damage, did not prevent increased neurogenesis in the granule cell layer after a subsequent severe ischemic challenge. Thus, ischemia-induced dentate neurogenesis is not attributable to CA1 neuronal loss. Enhanced neurogenesis in the dentate gyrus may be a compensatory adaptive response to ischemia-associated injury and could promote functional recovery after ischemic hippocampal injury. 0270-6474 Journal Article}, Author = {Liu, J. and Solway, K. and Messing, R. O. and Sharp, F. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurosci}, Keywords = {Dentate Gyrus/*blood supply/*cytology;Animals;Gerbillinae;Neurons/*cytology;Thymidine/pharmacokinetics;Ischemic Attack, Transient/*physiopathology;Cell Count;Stem Cells/cytology;Antimetabolites;Male;Entorhinal Cortex/blood supply/cytology;D abstr;Cell Division/physiology;06 Adult neurogenesis injury induced;Support, U.S. Gov't, P.H.S.;Cell Differentiation/physiology;Biological Markers;Bromodeoxyuridine;Astrocytes/cytology}, Number = {19}, Organization = {Departments of Neurology and Neurosurgery, University of California at San Francisco and San Francisco Veterans Affairs Medical Center, San Francisco, California 94121, USA.}, Pages = {7768-78}, Pubmed = {9742147}, Title = {Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils}, Uuid = {0EDB751A-EC81-11DA-8605-000D9346EC2A}, Volume = {18}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9742147}} @article{Liu:2003b, Abstract = {Several thousand new neurons are produced each day in the adult mammalian hippocampus, among which only excitatory granule cells (GCs) have thus far been identified. In the present study, we used mutant Semliki Forest Virus vectors to express enhanced green fluorescent protein in the hippocampus, and observed that approximately 14\%of newly generated neurons in the dentate gyrus of adult rats are GABAergic basket cells (BCs). With the use of double whole-cell patch-clamp recordings from BC-GC pairs in hippocampal slices, we demonstrate that newly generated BCs in the dentate gyrus form inhibitory synapses with principal GCs. These data show for the first time that functional inhibitory neurons are recruited in the dentate gyrus of adult rats. 1529-2401 Journal Article}, Author = {Liu, S. and Wang, J. and Zhu, D. and Fu, Y. and Lukowiak, K. and Lu, Y. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {J Neurosci}, Keywords = {Bromodeoxyuridine;A pdf;Neurons/classification/*cytology/metabolism/virology;Animals;Rats;Phenotype;Neural Inhibition/*physiology;Patch-Clamp Techniques;Female;Cell Count;Rats, Sprague-Dawley;Excitatory Postsynaptic Potentials/physiology;Genetic Vectors/administration &dosage/physiology;Isoenzymes/analysis/biosynthesis;Male;01 Adult neurogenesis general;Support, Non-U.S. Gov't;Synaptic Transmission/physiology;Cell Division/physiology;Hippocampus/*cytology/growth &development/virology;Cell Differentiation/physiology;Immunohistochemistry;Glutamate Decarboxylase/analysis/biosynthesis;gamma-Aminobutyric Acid/metabolism;Luminescent Proteins/genetics;Semliki forest virus/genetics/physiology;Genes, Reporter}, Number = {3}, Organization = {Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada, T2N 4N1.}, Pages = {732-6}, Title = {Generation of functional inhibitory neurons in the adult rat hippocampus}, Uuid = {DDD6D9F7-CCBF-442F-A5E2-CF720E0F5F4D}, Volume = {23}, Year = {2003}, url = {papers/Liu_JNeurosci2003.pdf}} @article{Liu:2003, Abstract = {Interneurons in the olfactory bulb (OB) are generated not only in the developing embryo but also throughout the postnatal life of mammals from neuronal precursor cells migrating from the anterior subventricular zone (SVZa) of the mammalian forebrain. We discovered that the OB secretes a diffusible activity that attracts these neuronal precursor cells. The attractive activity is present in specific layers in the OB, including the glomerular layer but not the granule cell layer. The attractive activity and the neuronal responsiveness persist from embryonic through neonatal to adult stages. Removal of the rostral OB significantly reduces SVZa migration toward the OB, an effect that can be rescued by a transplant of the OB but not by that of the neocortex. The activity in the OB is not mimicked by the known attractants. These results provide an explanation for the continuous migration of SVZa neurons toward the OB, demonstrate an important role of the OB in neuronal migration, and reveal the existence of a new chemoattractant. 1529-2401 Journal Article}, Author = {Liu, G. and Rao, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Neurons/*cytology/drug effects/physiology;Signal Transduction;Animals;In Vitro;Cells, Cultured;Rats;Coculture Techniques;Stem Cells/*cytology/drug effects/physiology;B pdf;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Cell Movement;Olfactory Bulb/cytology/embryology/*metabolism;Chemotactic Factors/pharmacology/*physiology;Olfactory Bulb;Prosencephalon;Support, Non-U.S. Gov't;Research Support, U.S. Gov't, P.H.S.;Cell Movement/drug effects/physiology;Coculture;Neurons;Support, U.S. Gov't, P.H.S.;Diffusion;Chemotactic Factors;Stem Cells;Gestational Age;Signal Transduction/physiology;Prosencephalon/*cytology/embryology/physiology}, Medline = {22761098}, Month = {7}, Nlm_Id = {8102140}, Number = {16}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.}, Pages = {6651-9}, Pii = {23/16/6651}, Pubmed = {12878706}, Title = {Neuronal migration from the forebrain to the olfactory bulb requires a new attractant persistent in the olfactory bulb}, Uuid = {B54BBF07-8397-4C07-9AFE-6F72BA0F4B6F}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12878706}} @article{Liu:2005, Abstract = {In the postnatal subventricular zone (SVZ), local cues or signaling molecules released from neuroblasts limit the proliferation of glial fibrillary acidic protein (GFAP)-expressing progenitors thought to be stem cells. However, signals between SVZ cells have not been identified. We show that depolarization of neuroblasts induces nonsynaptic SNARE-independent GABA(A) receptor currents in GFAP-expressing cells, the time course of which depends on GABA uptake in acute mouse slices. We found that GABA(A) receptors are tonically activated in GFAP-expressing cells, consistent with the presence of spontaneous depolarizations in neuroblasts that are sufficient to induce GABA release. These data demonstrate the existence of nonsynaptic GABAergic signaling between neuroblasts and GFAP-expressing cells. Furthermore, we show that GABA(A) receptor activation in GFAP-expressing cells limits their progression through the cell cycle. Thus, as GFAP-expressing cells generate neuroblasts, GABA released from neuroblasts provides a feedback mechanism to control the proliferation of GFAP-expressing progenitors by activating GABA(A) receptors.}, Author = {Liu, Xiuxin and Wang, Qin and Haydar, Tarik F. and Bordey, Ang{\'e}lique}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Research Support, N.I.H., Extramural;Spider Venoms;24 Pubmed search results 2008;Green Fluorescent Proteins;Sodium Channel Blockers;GABA Antagonists;Immunohistochemistry;Chelating Agents;10 Development;Animals;04 Adult neurogenesis factors;03 Adult neurogenesis progenitor source;Research Support, U.S. Gov't, P.H.S.;In Vitro;Egtazic Acid;Botulinum Toxins;Cell Count;Potassium;Electric Stimulation;Bromodeoxyuridine;Lateral Ventricles;Drug Interactions;Dose-Response Relationship, Radiation;Cyclooxygenase Inhibitors;Membrane Potentials;gamma-Aminobutyric Acid;Nickel;Gene Expression Regulation;Cadmium;Comparative Study;Glial Fibrillary Acidic Protein;Enzyme Inhibitors;Tetrodotoxin;Meclofenamic Acid;Patch-Clamp Techniques;Dose-Response Relationship, Drug;Stem Cells;Animals, Newborn;Cell Proliferation;Mice;Research Support, Non-U.S. Gov't;Neurons;Mice, Transgenic}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.}, Pages = {1179-87}, Pii = {nn1522}, Pubmed = {16116450}, Title = {Nonsynaptic GABA signaling in postnatal subventricular zone controls proliferation of GFAP-expressing progenitors}, Uuid = {63BEBDEF-E0E8-4922-99E1-7C281ED70367}, Volume = {8}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1522}} @article{Liu:2000, Abstract = {BETA2/NeuroD is a homologue of the Drosophila atonal gene that is widely expressed during development in the mammalian brain and pancreas. Although studies in Xenopus suggest that BETA2/NeuroD is involved in cellular differentiation, its function in the mammalian nervous system is unclear. Here we show that mutant mice homozygous for a deletion at the BETA2/NeuroD locus fail to develop a granule cell layer within the dentate gyrus, one of the principal structures of the hippocampal formation. To understand the basis of this abnormality, we analyzed dentate gyrus development by using immunocytochemical markers in BETA2/NeuroD-deficient mice. The early cell populations in the dentate gyrus, including Cajal-Retzius cells and radial glia, are present and appear normally organized. The migration of dentate precursor cells and newly born granule cells from the neuroepithelium to the dentate gyrus remains intact. However, there is a dramatic defect in the proliferation of precursor cells once they reach the dentate and a significant delay in the differentiation of granule cells. This leads to malformation of the dentate granule cell layer and excess cell death. BETA2/NeuroD null mice also exhibit spontaneous limbic seizures associated with electrophysiological evidence of seizure activity in the hippocampus and cortex. These findings thus establish a critical role of BETA2/NeuroD in the development of a specific class of neurons. Furthermore, failure to express BETA2/NeuroD leads to a stereotyped pattern of pathological excitability of the adult central nervous system.}, Author = {Liu, M. and Pleasure, S. J. and Collins, A. E. and Noebels, J. L. and Naya, F. J. and Tsai, M. J. and Lowenstein, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Differentiation;Animals;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Trans-Activators;Mice, Mutant Strains;Phenotype;Female;Epilepsy;Mutation;Hippocampus;Mice, Inbred C57BL;Male;In Situ Hybridization;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred Strains;Neurons;Dentate Gyrus;Genotype;Mice;Cell Division;Limbic System;Research Support, Non-U.S. Gov't}, Medline = {20105564}, Month = {1}, Nlm_Id = {7505876}, Number = {2}, Organization = {Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.}, Pages = {865-70}, Pubmed = {10639171}, Title = {Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy}, Uuid = {3210BAF0-716F-11DA-A383-000D9346EC2A}, Volume = {97}, Year = {2000}, url = {papers/Liu_ProcNatlAcadSciUSA2000.pdf}} @article{Livet:2007, Abstract = {Detailed analysis of neuronal network architecture requires the development of new methods. Here we present strategies to visualize synaptic circuits by genetically labelling neurons with multiple, distinct colours. In Brainbow transgenes, Cre/lox recombination is used to create a stochastic choice of expression between three or more fluorescent proteins (XFPs). Integration of tandem Brainbow copies in transgenic mice yielded combinatorial XFP expression, and thus many colours, thereby providing a way to distinguish adjacent neurons and visualize other cellular interactions. As a demonstration, we reconstructed hundreds of neighbouring axons and multiple synaptic contacts in one small volume of a cerebellar lobe exhibiting approximately 90 colours. The expression in some lines also allowed us to map glial territories and follow glial cells and neurons over time in vivo. The ability of the Brainbow system to label uniquely many individual cells within a population may facilitate the analysis of neuronal circuitry on a large scale.}, Author = {Livet, Jean and Weissman, Tamily A. and Kang, Hyuno and Draft, Ryan W. and Lu, Ju and Bennis, Robyn A. and Sanes, Joshua R. and Lichtman, Jeff W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Transgenes;Animals;Synapses;Humans;Neural Pathways;Nervous System;Cell Communication;Integrases;Mice, Transgenic;Axons;Color;Time Factors;Cell Line;Genetic Engineering;Neuroglia;Recombination, Genetic;Cerebellum;Mice;24 Pubmed search results 2008;Luminescent Proteins;Attachment Sites, Microbiological;Gene Expression;Stochastic Processes}, Month = {11}, Nlm_Id = {0410462}, Number = {7166}, Organization = {Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.}, Pages = {56-62}, Pii = {nature06293}, Pubmed = {17972876}, Title = {Transgenic strategies for combinatorial expression of fluorescent proteins in the nervous system}, Uuid = {EE8EF728-7540-4FDE-9AC1-5C297F7A8DC0}, Volume = {450}, Year = {2007}, url = {papers/Livet_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06293}} @article{Livnat:2006, Abstract = {Many behaviors have been attributed to internal conflict within the animal and human mind. However, internal conflict has not been reconciled with evolutionary principles, in that it appears maladaptive relative to a seamless decision-making process. We study this problem through a mathematical analysis of decision-making structures. We find that, under natural physiological limitations, an optimal decision-making system can involve "selfish" agents that are in conflict with one another, even though the system is designed for a single purpose. It follows that conflict can emerge within a collective even when natural selection acts on the level of the collective only.}, Author = {Livnat, and Pippenger,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {7505876}, Organization = {Departments of Ecology and Evolutionary Biology and Computer Science, Princeton University, Princeton, NJ 08540.}, Pii = {0510932103}, Pubmed = {16492775}, Title = {An optimal brain can be composed of conflicting agents}, Uuid = {4C83BE74-1CF5-4E70-B908-AFA8843A67D3}, Year = {2006}, url = {papers/Livnat_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0510932103}} @article{Lledo:2006, Abstract = {The adult brain is a plastic place. To ensure that the mature nervous system's control of behaviour is flexible in the face of a varying environment, morphological and physiological changes are possible at many levels, including that of the entire cell. In two areas of the adult brain - the olfactory bulb and the dentate gyrus - new neurons are generated throughout life and form an integral part of the normal functional circuitry. This process is not fixed, but highly modulated, revealing a plastic mechanism by which the brain's performance can be optimized for a given environment. The functional benefits of this whole-cell plasticity, however, remain a matter for debate.}, Author = {Lledo, Pierre-Marie M. and Alonso, Mariana and Grubb, Matthew S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {100962781}, Number = {3}, Organization = {Laboratory of Perception and Memory, Institut Pasteur, Centre National de la Recherche Scientifique Unit de Recherche Associ{\'e}e 2182, 25, rue du Docteur Roux, 75724 Paris cedex 15, France. pmlledo\@pasteur.fr}, Pages = {179-93}, Pii = {nrn1867}, Pubmed = {16495940}, Title = {Adult neurogenesis and functional plasticity in neuronal circuits}, Uuid = {E8E2FDD5-5F5A-4926-8606-206EE258A351}, Volume = {7}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1867}} @article{Lledo:2003, Abstract = {The perception of odorant molecules provides the essential information that allows animals to explore their surrounding. We describe here how the external world of scents may sculpt the activity of the first central relay of the olfactory system, i.e., the olfactory bulb. This structure is one of the few brain areas to continuously replace one of its neuronal populations: the local GABAergic interneurons. How the newly generated neurons integrate into a pre-existing neural network and how basic olfactory functions are maintained when a large percentage of neurons are subjected to continuous renewal, are important questions that have recently received new insights. Furthermore, we shall see how the adult neurogenesis is specifically subjected to experience-dependent modulation. In particular, we shall describe the sensitivity of the bulbar neurogenesis to the activity level of sensory inputs from the olfactory epithelium and, in turn, how this neurogenesis may adjust the neural network functioning to optimize odor information processing. Finally, we shall discuss the behavioral consequences of the bulbar neurogenesis and how it may be appropriate for the sense of smell. By maintaining a constitutive turnover of bulbar interneurons subjected to modulation by environmental cues, we propose that adult ongoing neurogenesis in the olfactory bulb is associated with improved olfactory memory. These recent findings not only provide new fuel for the molecular and cellular bases of sensory perception but should also shed light onto cellular bases of learning and memory. 0959-4965 Journal Article Review Review, Tutorial}, Author = {Lledo, P. M. and Gheusi, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Neuroreport}, Keywords = {Odors;01 Adult neurogenesis general;gamma-Aminobutyric Acid/physiology;Smell/*physiology;Olfactory Bulb/cytology/*physiology;Mitosis/*physiology;Memory/*physiology;Neuronal Plasticity;Cell Death;Mammals/physiology;Interneurons/*physiology;Support, Non-U.S. Gov't;Animals;Learning/physiology;A pdf}, Number = {13}, Organization = {Laboratory of Perception and Memory, Centre National de la Recherche Scientifique, Unite de Recherche Associee 2182, Institut Pasteur, 25 rue du Dr. Roux, 75724 Paris, France. pmlledo\@pasteur.fr}, Pages = {1655-63}, Pubmed = {14512833}, Title = {Olfactory processing in a changing brain}, Uuid = {77B8E530-AB82-4CA8-B88B-FF4B63F41CF7}, Volume = {14}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14512833}} @article{Lo:2001, Author = {Lo, D. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:52 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Biomedical Technology;Gene Expression Regulation, Developmental;Drug Industry;Human;Neurosciences;Time Factors;review, tutorial;Genomic Library;Animals;Central Nervous System Diseases;review;23 Technique}, Medline = {21547534}, Month = {11}, Nlm_Id = {9809671}, Organization = {Cogent Neuroscience, Inc. 4321 Medical Park Drive Durham, NC 27704, USA.}, Pages = {1153-4}, Pii = {nn1101-1153}, Pubmed = {11687820}, Title = {Challenges for neuroscience in a post-genome world}, Uuid = {589AB5B1-3FED-497D-8C84-6256F0A8B98D}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Lo_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1101-1153}} @article{LoTurco:2003, Abstract = {Successful cell division in neural progenitors in the neocortical ventricular zone (VZ), as in all dividing cells, depends critically upon coordinating chromosome segregation during mitosis with cytokinesis. This coordination further suggests that common molecular regulators may link events in mitosis with those in cytokinesis. Recent genetic evidence indicates that cytokinesis in CNS neuronal progenitors, but not in most other cell types of the body, requires the function of citron kinase. In neocortex, citron kinase is most critical for neurogenic cytokinesis. In citron kinase null mutants, a large proportion of neuronal cells within neocortex are binucleate; however, very few glial cells are binucleate. In addition, confocal time-lapse imaging of mitoses at the VZ surface shows that citron kinase is also necessary for phases of the cell cycle just prior to cytokinesis. Deficits in mitosis seen in mutants indicate aberrant mitotic spindle function, and like deficits in cytokinesis, occur in some but not all cells at the VZ surface. Citron kinase is therefore an essential multifunctional regulator of cell divisions in the VZ, and may serve to coordinate chromosome segregation with cytokinesis in neuronal precursors.}, Author = {LoTurco, Joseph J. and Sarkisian, Mathew R. and Cosker, Laurie and Bai, Jilin}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Mice, Knockout;Rats;Research Support, U.S. Gov't, P.H.S.;Neocortex;Cell Division;Rats, Mutant Strains;Mice, Mutant Strains;Protein-Serine-Threonine Kinases;Culture Techniques;Mitosis;Cerebral Ventricles;Animals;Mice;Neurons}, Medline = {22648196}, Month = {6}, Nlm_Id = {9110718}, Number = {6}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269-4156, USA. Loturco\@uconn.edu}, Pages = {588-91}, Pubmed = {12764032}, Title = {Citron kinase is a regulator of mitosis and neurogenic cytokinesis in the neocortical ventricular zone}, Uuid = {979B27FA-69B0-11DA-A4B6-000D9346EC2A}, Volume = {13}, Year = {2003}, url = {papers/LoTurco_CerebCortex2003.pdf}} @article{LoTurco:1995, Abstract = {We have found that, during the early stages of cortical neurogenesis, both GABA and glutamate depolarize cells in the ventricular zone of rat embryonic neocortex. In the ventricular zone, glutamate acts on AMPA/kainate receptors, while GABA acts on GABAA receptors. GABA induces an inward current at resting membrane potentials, presumably owing to a high intracellular Cl- concentration maintained by furosemide-sensitive Cl- transport. GABA and glutamate also produce increases in intracellular Ca2+ in ventricular zone cells, in part through activation of voltage-gated Ca2+ channels. Furthermore, GABA and glutamate decrease the number of embryonic cortical cells synthesizing DNA. Depolarization with K+ similarly decreases DNA synthesis, suggesting that the neurotransmitters act via membrane depolarization. Applied alone, GABAA and AMPA/kainate receptor antagonists increase DNA synthesis, indicating that endogenously released amino acids influence neocortical progenitors in the cell cycle. These results demonstrate a novel role for amino acid neurotransmitters in regulating neocortical neurogenesis.}, Author = {LoTurco, J. J. and Owens, D. F. and Heath, M. J. and Davis, M. B. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Neuron}, Keywords = {Glutamic Acid/*pharmacology;GABA/*pharmacology;10 Development;Rats, Sprague-Dawley;Stem Cells/*drug effects/*metabolism;Cell Polarity/drug effects;Rats;DNA/*biosynthesis;Cerebral Cortex/*cytology/embryology/metabolism;Animal;F;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Patch-Clamp Techniques}, Number = {6}, Organization = {Department of Physiology and Neurobiology, University of Connecticut at Storrs 06269, USA.}, Pages = {1287-98.}, Title = {GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis}, Uuid = {FF0E3C5E-D06B-11DA-8A8C-000D9346EC2A}, Volume = {15}, Year = {1995}, url = {papers/LoTurco_Neuron1995.pdf}} @article{Locatelli:2003, Abstract = {Recent evidence suggests that cells from bone marrow can acquire neuroectodermal phenotypes in cell culture or after transplantation in animal models and in the human brain. However, isolation of the bone marrow cell subpopulation with neuronal differentiation potential remains a challenge. To isolate and expand neural progenitors from whole murine bone marrow, bone marrow was obtained from hind limb bone of C57BL6 mice and plated in culture with neuronal medium with basic fibroblast growth factor and epidermal growth factor. After 5-7 days in culture, cellular spheres similar to brain neurospheres appeared either floating or attached to culture dishes. These spheres were collected, dissociated, and expanded. The bone marrow-derived spheres were positive for nestin as assessed by immunocytochemistry and by reverse transcriptase polymerase chain reaction. Thy-1- and Sca-1-positive bone marrow cells selected by magnetic cell sorting resulted in a higher yield of nestin-positive spheres. After exposure to neuronal differentiative medium retinoic acid with and without Sonic hedgehog, cells positive for neuronal markers tubulin III (TuJ-1) and neurofilament (NF) were detected. The mRNA profile of these cells included the expression of TuJ-1, neuronal-specific enolase (NSE), and NF-light chain. To evaluate the in vivo behavior of these cells, spheres derived from bone marrow-derived cells of transgenic green fluorescent protein (GFP) mice were transplanted into newborn mouse brain. Two months later, the mouse neural cortex contained a minor proportion of GFP(+) cells co-expressing neuronal markers (TuJ-1, NF, MAP-2, NeuN). Although cell fusion phenomena with the host cells could not be ruled out, bone marrow-derived neurosphere transplantation could be a strategy for cellular mediated gene therapy.}, Author = {Locatelli, F. and Corti, S. and Donadoni, C. and Guglieri, M. and Capra, F. and Strazzer, S. and Salani, S. and Del Bo, R. and Fortunato, F. and Bordoni, A. and Comi, G. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1525-8165}, Journal = {J Hematother Stem Cell Res}, Keywords = {Tretinoin;Cell Differentiation;Phosphopyruvate Hydratase;Antigens, Thy-1;Green Fluorescent Proteins;Immunohistochemistry;Luminescent Proteins;Brain;Animals;Epidermal Growth Factor;Intermediate Filament Proteins;Fibroblast Growth Factor 2;Gene Expression;Bone Marrow Transplantation;Mice, Inbred C57BL;Neurofilament Proteins;Tubulin;11 Glia;Antigens, Ly;Cell Adhesion;Proto-Oncogene Protein c-kit;Glial Fibrillary Acidic Protein;Neuroglia;Immunomagnetic Separation;Membrane Proteins;Bone Marrow Cells;Animals, Newborn;Stem Cells;Microscopy, Confocal;Mice;Research Support, Non-U.S. Gov't;Neurons;Mice, Transgenic;Reverse Transcriptase Polymerase Chain Reaction;Nerve Tissue Proteins;Trans-Activators}, Month = {12}, Nlm_Id = {100892915}, Number = {6}, Organization = {Centro Dino Ferrari, Dipartimento di Scienze Neurologiche, Universit\`{a} degli Studi di Milano, I.R.C.C.S. Ospedale Maggiore Policlinico, Milan, Italy.}, Pages = {727-34}, Pubmed = {14977481}, Title = {Neuronal differentiation of murine bone marrow Thy-1- and Sca-1-positive cells}, Uuid = {A8A7A0C0-D3A3-4E60-9FFC-3841F44311AC}, Volume = {12}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/15258160360732740}} @article{Loewen:2004, Abstract = {PURPOSE: To address a problem impeding research into glaucoma-associated genetic mutations and glaucoma gene therapy and achieve permanent, targeted transgene expression in the trabecular meshwork (TM). Lentiviral vectors are known to transduce human donor eye TM ex vivo, but efficacy in vivo has not been shown. More generally in the field of gene therapy, the authors hypothesized that distinctive properties of the intraocular aqueous circulation could facilitate solving problems of accessibility, targeting, and scale that have hindered realization of gene therapy in other settings. METHODS: A domestic cat model was developed in which long-term in vivo studies were performed. After dose-response studies in primary human TM cells, 19 cats received anterior chamber (AC) injections of stepped doses (10(6)-10(8) transduction units) of lentiviral vectors encoding different marker transgenes (beta-galactosidase, Aequorea victoria green fluorescent protein [GFP], or Renilla reniformis GFP). Animals were monitored serially for transgene expression and IOP. RESULTS: High-grade, stable transgene expression in the TM was achieved and monitored noninvasively over time in living animals. Extensive expression resulted after a single transcorneal injection, persisted for at least 10 months (time of death in the present studies), and was targeted to the TM. The initial IOP did not differ significantly from the IOP at the end of the study (P = 0.4). Aequorea GFP was superior to Renilla GFP. Vectors were effective enough to cause GFP-specific overexpression cytotoxicity at the highest dose, which was solved by dose reduction. CONCLUSIONS: High-grade transgene expression in this large-animal model persisted stably for at least 10 months after a single transcorneal lentiviral vector injection, was highly targeted, and could be monitored serially and noninvasively in living animals. These studies provide a basis for developing realistic disease models and administering glaucoma gene therapy.}, Author = {Loewen, Nils and Fautsch, Michael P. and Teo, Wu-Lin L. and Bahler, Cindy K. and Johnson, Douglas H. and Poeschla, Eric M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0146-0404}, Journal = {Invest Ophthalmol Vis Sci}, Keywords = {Transgenes;Transduction, Genetic;beta-Galactosidase;Gene Targeting;Humans;Cells, Cultured;Animals;Lentivirus;Indicators and Reagents;Animals, Genetically Modified;11 Glia;Green Fluorescent Proteins;Time Factors;Genetic Vectors;Intraocular Pressure;Trabecular Meshwork;Research Support, U.S. Gov't, P.H.S.;Aqueous Humor;Luminescent Proteins;Cats;Gene Expression;Research Support, Non-U.S. Gov't}, Month = {9}, Nlm_Id = {7703701}, Number = {9}, Organization = {Molecular Medicine Program, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.}, Pages = {3091-8}, Pii = {45/9/3091}, Pubmed = {15326125}, Title = {Long-term, targeted genetic modification of the aqueous humor outflow tract coupled with noninvasive imaging of gene expression in vivo}, Uuid = {12AB1D7D-6598-444B-9A91-E5DD606B5FDF}, Volume = {45}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1167/iovs.04-0366}} @article{Logothetis:2007, Abstract = {To combine insights obtained from electric field potentials (LFPs) and neuronal spiking activity (MUA) we need a better understanding of the relative spatial summation of these indices of neuronal activity. Compared to MUA, the LFP has greater spatial coherence, resulting in lower spatial specificity and lower stimulus selectivity. A differential propagation of low- and high-frequency electric signals supposedly underlies this phenomenon, which could result from cortical tissue specifically attenuating higher frequencies, i.e., from a frequency-dependent impedance spectrum. Here we directly measure the cortical impedance spectrum in vivo in monkey primary visual cortex. Our results show that impedance is independent of frequency, is homogeneous and tangentially isotropic within gray matter, and can be theoretically predicted assuming a pure-resistive conductor. We propose that the spatial summation of LFP and MUA is determined by the size of these signals' generators and the nature of neural events underlying them, rather than by biophysical properties of gray matter.}, Author = {Logothetis, Nikos K. and Kayser, Christoph and Oeltermann, Axel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Electrophysiology;Animals;Evoked Potentials;Signal Processing, Computer-Assisted;Neural Pathways;Neural Conduction;Synaptic Transmission;Axons;Nerve Fibers, Myelinated;research support, non-u.s. gov't;Action Potentials;Neuropil;Electric Impedance;21 Neurophysiology;Haplorhini;Neurons;24 Pubmed search results 2008;Visual Cortex;Models, Neurological}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 T{\"u}bingen, Germany. nikos.logothetis\@tuebingen.mpg.de}, Pages = {809-23}, Pii = {S0896-6273(07)00572-7}, Pubmed = {17785187}, Title = {In vivo measurement of cortical impedance spectrum in monkeys: implications for signal propagation}, Uuid = {05154D79-4F30-44F1-9AF9-87FE6D4E34E1}, Volume = {55}, Year = {2007}, url = {papers/Logothetis_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.07.027}} @article{Lohmann:2008, Abstract = {Synapse elimination is an important process underlying the establishment of functional neuronal networks during development. Here, we tested the idea that neurons select among potential synaptic partners already during initial contact formation between dendritic filopodia and axons-well before mature synapses are established. We show that filopodia frequently make contact with axons, and while some contacts are selectively stabilized, many are short-lived. More specifically, we demonstrate that contacts with a certain population of GABAergic axons never get stabilized, indicating that filopodia already early on select between different types of axons. Local dendritic calcium transients that are independent of glutamate occur within seconds after contact formation, and their frequency is high where contacts become stabilized and low at short-lived contacts. Thus, filopodia are capable of choosing between potential synaptic partners well before a mature synapse is established.}, Author = {Lohmann, Christian and Bonhoeffer, Tobias}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {Synapses;research support, non-u.s. gov't;Dendrites;Rats;Pseudopodia;comparative study;Animals, Newborn;Calcium Signaling;Animals;Cells, Cultured;Mice;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {8809320}, Number = {2}, Organization = {Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Planegg-Martinsried, Germany. c.lohmann\@nin.knaw.nl}, Pages = {253-60}, Pii = {S0896-6273(08)00460-1}, Pubmed = {18667153}, Title = {A role for local calcium signaling in rapid synaptic partner selection by dendritic filopodia}, Uuid = {7EC30ACE-D419-43D5-9FBD-7F2411A6739F}, Volume = {59}, Year = {2008}, url = {papers/Lohmann_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.05.025}} @article{Lois:1993, Abstract = {Subventricular zone (SVZ) cells proliferate spontaneously in vivo in the telencephalon of adult mammals. Several studies suggest that SVZ cells do not differentiate after mitosis into neurons or glia but die. In the present work, we show that SVZ cells labeled in the brains of adult mice with [3H]thymidine differentiate directly into neurons and glia in explant cultures. In vitro labeling with [3H]thymidine shows that 98\%of the neurons that differentiate from the SVZ explants are derived from precursor cells that underwent their last division in vivo. This report identifies the SVZ cells as neuronal precursors in an adult mammalian brain.}, Author = {Lois, C. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Prosencephalon/*cytology;Support, Non-U.S. Gov't;02 Adult neurogenesis migration;Cell Differentiation;Cerebral Ventricles/cytology;03 Adult neurogenesis progenitor source;Cell Division;Neuroglia/*cytology;In Vitro;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Animal;Mice;Cells, Cultured;Stem Cells/cytology;BB abstr;Corpus Striatum/cytology}, Number = {5}, Organization = {Rockefeller University, New York, NY 10021.}, Pages = {2074-7.}, Title = {Proliferating subventricular zone cells in the adult mammalian forebrain can differentiate into neurons and glia}, Uuid = {757FF8C8-F7DA-482E-9DDA-0EB28C3C5B0B}, Volume = {90}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8446631}} @article{Lois:1994, Abstract = {During the development of the mammalian brain, neuronal precursors migrate to their final destination from their site of birth in the ventricular and subventricular zones (VZ and SVZ, respectively). SVZ cells in the walls of the lateral ventricle continue to proliferate in the brain of adult mice and can generate neurons in vitro, but their fate in vivo is unknown. Here SVZ cells from adult mice that carry a neuronal-specific transgene were grafted into the brain of adult recipients. In addition, the fate of endogenous SVZ cells was examined by microinjection of tritiated thymidine or a vital dye that labeled a discrete population of SVZ cells. Grafted and endogenous SVZ cells in the lateral ventricle of adult mice migrate long distances and differentiate into neurons in the olfactory bulb.}, Author = {Lois, C. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Science}, Keywords = {Cerebral Ventricles/*cytology;Cell Differentiation;Neurons/*cytology/metabolism;Olfactory Bulb/*cytology;Microinjections;Brain Tissue Transplantation;beta-Galactosidase/analysis/genetics;Animal;Cell Movement;Mice, Transgenic;A-6;Brain/cytology;Mice, Inbred Strains;Support, Non-U.S. Gov't;Cell Transplantation;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Genes, Reporter}, Number = {5162}, Organization = {Rockefeller University, New York, NY 10021.}, Pages = {1145-8.}, Title = {Long-distance neuronal migration in the adult mammalian brain}, Uuid = {120AE247-CD62-11D9-97C9-000D9346EC2A}, Volume = {264}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8178174}} @article{Lois:1996, Abstract = {In the brain of adult mice, cells that divide in the subventricular zone of the lateral ventricle migrate up to 5 millimeters to the olfactory bulb where they differentiate into neurons. These migrating cells were found to move as chains through a well-defined pathway, the rostral migratory stream. Electron microscopic analysis of serial sections showed that these chains contained only closely apposed, elongated neuroblasts connected by membrane specializations. A second cell type, which contained glial fibrillary acidic protein, ensheathed the chains of migrating neuroblasts. Thus, during chain migration, neural precursors moved associated with each other and were not guided by radial glial or axonal fibers.}, Author = {Lois, C. and Garcia-Verdugo, J. M. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Science}, Keywords = {Cerebral Ventricles/*cytology;Cell Differentiation;Neural Cell Adhesion Molecules/analysis;Cell Membrane/ultrastructure;B abstr;Neuroglia/chemistry/*cytology/physiology;Neurons/*cytology/ultrastructure;Mitosis;Animal;Cell Movement;02 Adult neurogenesis migration;Glial Fibrillary Acidic Protein/analysis;Male;Support, Non-U.S. Gov't;Olfactory Bulb/cytology;Support, U.S. Gov't, P.H.S.;Mice;Microscopy, Electron}, Number = {5251}, Organization = {Rockefeller University, New York 10021, USA.}, Pages = {978-81.}, Title = {Chain migration of neuronal precursors}, Uuid = {D5824B12-8D9D-436E-82DF-65DA6355AF61}, Volume = {271}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8584933}} @article{Lombroso:2000, Abstract = {PURPOSE: Increased availability of surgically resected epileptogenic tissues reveals often unsuspected cortical dysplasia (CD). There is some controversy about the ontogenic stages in which these occur. Although most take place during neuroblast proliferation and migration, there is some evidence for some CD occurring during postmigrational intrinsic cortical organization. It has been shown that various kinds of focal cortical manipulations in rats, if performed within 3-4 postnatal days, lead to the genesis of various cortical malformations including a four-layered microgyrus or an unlayered CD. It is not known whether such events also might occur in the human brain. METHODS: Two children sustained minor head trauma within 4 postnatal days and later developed intractable epilepsy, which was relieved by surgery. Neuropathologic analysis of the resected tissues revealed an unsuspected microdysplastic cortex immediately adjacent to a focal, modest meningeal fibrosis, presumably secondary to the old closed head trauma. RESULTS: The main histologic features were a disorganized, unlayered cortex; abnormal clusters of neurons, often with complex, randomly oriented proximal dendritic patterns with absent apical orientation; the presence of a number of heterotopic small and large neurons in the white matter; absence of inflammatory infiltrates, of hemosiderine, of reactive gliosis, or of an excessive number of blood vessels. The morphologic features in these surgical specimens suggest that these focal malformations occur because of a regional disorder of postmigrational intrinsic cortical remodeling. CONCLUSIONS: The clinical histories and the pathologic findings lend some support to the hypothesis that minor morbid events occuring in the immediate postnatal period may lead to microdysplasia in the human similar to those induced in rat pups. The animal model could be helpful to clarify the genesis of some cases of CD and of the epileptogenicity often manifesting later in life.}, Author = {Lombroso, C. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:51 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {10 Development;case reports;Electric Stimulation;Animals;Craniocerebral Trauma;Humans;Rats;21 Epilepsy;Female;Epilepsy;Disease Models, Animal;Animals, Newborn;Nervous System Malformations;Cerebral Cortex;21 Neurophysiology;10 genetics malformation;24 Pubmed search results 2008;Electroencephalography;Adolescent}, Medline = {20152984}, Month = {2}, Nlm_Id = {2983306R}, Number = {2}, Organization = {Department of Neurology, Children's Hospital and Harvard Medical School, Boston, Massachusetts, USA. Lombroso C\@aol.com}, Pages = {245-53}, Pubmed = {10691125}, Title = {Can early postnatal closed head injury induce cortical dysplasia}, Uuid = {AB33617D-B9B8-456E-AF3F-ED771C4058A6}, Volume = {41}, Year = {2000}, url = {papers/Lombroso_Epilepsia2000.pdf}} @article{Lomvardas:2006, Abstract = {The expression of a single odorant receptor (OR) gene from a large gene family in individual sensory neurons is an essential feature of the organization and function of the olfactory system. We have used chromosome conformation capture to demonstrate the specific association of an enhancer element, H, on chromosome 14 with multiple OR gene promoters on different chromosomes. DNA and RNA fluorescence in situ hybridization (FISH) experiments allow us to visualize the colocalization of the H enhancer with the single OR allele that is transcribed in a sensory neuron. In transgenic mice bearing additional H elements, sensory neurons that express OR pseudogenes also express a second functional receptor. These data suggest a model of receptor choice in which a single trans-acting enhancer element may allow the stochastic activation of only one OR allele in an olfactory sensory neuron.}, Author = {Lomvardas, Stavros and Barnea, Gilad and Pisapia, David J. and Mendelsohn, Monica and Kirkland, Jennifer and Axel, Richard}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Chromosomes;In Situ Hybridization, Fluorescence;research support, n.i.h., extramural ;Animals;RNA;Gene Expression Regulation;Olfactory Receptor Neurons;DNA;09 Evolutionary dynamics;Pseudogenes;Neurons, Afferent;Mice, Transgenic;Enhancer Elements (Genetics);research support, non-u.s. gov't ;Sulfites;Alleles;Multigene Family;Receptors, Odorant;Mice;Promoter Regions (Genetics);24 Pubmed search results 2008;DNA Methylation}, Month = {7}, Nlm_Id = {0413066}, Number = {2}, Organization = {Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.}, Pages = {403-13}, Pii = {S0092-8674(06)00855-5}, Pubmed = {16873069}, Title = {Interchromosomal interactions and olfactory receptor choice}, Uuid = {41BEF53D-8E67-4832-906F-E5785AFE3D98}, Volume = {126}, Year = {2006}, url = {papers/Lomvardas_Cell2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.06.035}} @article{Long:2007, Abstract = {Olfactory bulb interneuron development is a complex multistep process that involves cell specification in the ventral telencephalon, tangential migration into the olfactory bulb, and local neuronal maturation. Although several transcription factors have been implicated in this process, how or when they act remains to be elucidated. Here we explore the mechanisms that result in olfactory bulb interneuron defects in Dlx1&2-/- (distal-less homeobox 1 and 2) and Mash1-/- (mammalian achaete-schute homolog 1) mutants. We provide evidence that Dlx1&2 and Mash1 regulate parallel molecular pathways that are required for the generation of these cells, thereby providing new insights into the mechanisms underlying olfactory bulb development. The analysis also defined distinct anatomical zones related to olfactory bulb development. Finally we show that Dlx1&2 are required for promoting tangential migration to the olfactory bulb, potentially via regulating the expression of ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4), Robo2 (roundabout homolog 2), Slit1 (slit homolog 1), and PK2 (prokineticin 2), which have all been shown to play essential roles in this migration.}, Author = {Long, Jason E. and Garel, Sonia and Alvarez-Dolado, Manuel and Yoshikawa, Kazuaki and Osumi, Noriko and Alvarez-Buylla, Arturo and Rubenstein, John L. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {13 Olfactory bulb anatomy;Cell Differentiation;Signal Transduction;Animals;Transcription Factors;Mice, Mutant Strains;comparative study;Homeodomain Proteins;Cell Movement;02 Adult neurogenesis migration;Mice, Inbred C57BL;research support, non-u.s. gov't;Olfactory Bulb;Mice, Knockout;research support, n.i.h., extramural;Mice;Interneurons;24 Pubmed search results 2008;12 Interneuron development}, Month = {3}, Nlm_Id = {8102140}, Number = {12}, Organization = {Nina Ireland Laboratory of Developmental Neurobiology, University of California at San Francisco, San Francisco, California 94143, USA.}, Pages = {3230-43}, Pii = {27/12/3230}, Pubmed = {17376983}, Title = {Dlx-dependent and -independent regulation of olfactory bulb interneuron differentiation}, Uuid = {3B0B3C65-4D6B-448B-B6EA-A9ED898FCF6A}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5265-06.2007}} @article{Lopez-Garcia:2002, Abstract = {The medial cerebral cortex of lizards, an area homologous to the hippocampal fascia dentata, shows delayed postnatal neurogenesis, i.e., cells in the medial cortex ependyma proliferate and give rise to immature neurons, which migrate to the cell layer. There, recruited neurons differentiate and give rise to zinc containing axons directed to the rest of cortical areas, thus resulting in a continuous growth of the medial cortex and its zinc-enriched axonal projection. This happens along the lizard life span, even in adult lizards, thus allowing one of their most important characteristics: neuronal regeneration. Experiments in our laboratory have shown that chemical lesion of the medial cortex (affecting up to 95\%of its neurons) results in a cascade of events: first, massive neuronal death and axonal-dendritic retraction and, secondly, triggered ependymal-neuroblast proliferation and subsequent neo-histogenesis and regeneration of an almost new medial cortex, indistinguishable from a normal undamaged one. This is the only case to our knowledge of the regeneration of an amniote central nervous centre by new neuron production and neo-histogenesis. Thus the lizard cerebral cortex is a good model to study neuronal regeneration and the complex factors that regulate its neurogenetic, migratory and neo-synaptogenetic events.}, Author = {Lopez-Garcia, Carlos and Molowny, Asuncion and Nacher, Juan and Ponsoda, Xavier and Sancho-Bielsa, Francisco and Alonso-Llosa, Gregori}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0001-3765}, Journal = {An Acad Bras Cienc}, Keywords = {review;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Models, Animal;Nerve Regeneration;review, tutorial;Lizards;Animals;Cerebral Cortex;Neurons;Seasons}, Medline = {21955951}, Month = {3}, Nlm_Id = {7503280}, Number = {1}, Organization = {Lab. Neurobiologia Celular, Universidad de Valencia, Burjasot, Valencia, 46100, Spain. carlos.lopez\@uv.es}, Pages = {85-104}, Pii = {S0001-37652002000100006}, Pubmed = {11960178}, Title = {The lizard cerebral cortex as a model to study neuronal regeneration}, Uuid = {7D2759FB-FB2F-4E53-84DB-EE7E1CA9353C}, Volume = {74}, Year = {2002}} @article{Lopez-Garcia:1994, Abstract = {In normal lizards, microglial cells populate the medial cortex (a zone homologous to the hippocampal fascia dentata), with a preferential distribution along the border between the granular cell layer and the plexiform layers. Intraperitoneal injection of the neurotoxin 3-acetylpyridine (3AP) induces a selective lesion in the medial cortex with a rapid degeneration of the granular layer and its zinc-enriched axonal projection. Within 6-8 weeks, the granular layer is, however, repopulated by a new set of neurons generated in the subjacent ependyma and the cell debris is removed. The aim of this study was to determine to what extent microglia were involved in the scavenging processes during the regeneration process. To this end we studied the brains of regenerating lizards at different times after 3AP lesion, visualising microglial cells by the nucleoside diphosphatase (NDPase) histochemical reaction. Surprisingly, we found that stained microglial cells disappeared 6-8 hours after 3AP injection and remained absent until 10-15 days after injection. One month postlesion an increased population of microglial cells was found scattered throughout all plexiform layers of the cortex. Thorough examination of semithin and ultrathin sections confirmed the absence of microglia in the medial cortex of recent lesioned animals but the presence of an exuberant population after 1 month postlesion. In the tissue, phagocytotic scavenging was carried out by radial ependymocytes, not by microglia.}, Author = {Lopez-Garcia, C. and Nacher, J. and Castellano, B. and Luis de la Iglesia, J. A. and Molowny, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Acid Anhydride Hydrolases;Nerve Regeneration;Hippocampus;Microscopy, Electron;Pyridines;Not relevant;11 Glia;Microglia;Histocytochemistry;Lizards;Support, Non-U.S. Gov't;Animals;Phagocytosis}, Medline = {95146147}, Month = {9}, Nlm_Id = {8806785}, Number = {1}, Organization = {Facultad de Ciencias Biologicas, Universidad de Valencia, Burjasot, Spain.}, Pages = {52-61}, Pubmed = {7843787}, Title = {Transitory disappearance of microglia during the regeneration of the lizard medial cortex}, Uuid = {D39F8439-0332-4FC1-B75C-D5E9E4DE039D}, Volume = {12}, Year = {1994}} @article{Lossi:2003, Abstract = {Apoptosis has been recognized to be an essential process during neural development. It is generally assumed that about half of the neurons produced during neurogenesis die before completion of the central nervous system (CNS) maturation, and this process affects nearly all classes of neurons. In this review, we discuss the experimental data in vivo on naturally occurring neuronal death in normal, transgenic and mutant animals, with special attention to the cerebellum as a study model. The emerging picture is that of a dual wave of apoptotic cell death affecting central neurons at different stages of their life. The first wave consists of an early neuronal death of proliferating precursors and young postmitotic neuroblasts, and appears to be closely linked to cell cycle regulation. The second wave affects postmitotic neurons at later stages, and is much better understood in functional terms, mainly on the basis of the neurotrophic concept in its broader definition. The molecular machinery of late apoptotic death of postmitotic neurons more commonly follows the mitochondrial pathway of intracellular signal transduction, but the death receptor pathway may also be involved.Undoubtedly, analysis of naturally occurring neuronal death (NOND) in vivo will offer a basis for parallel and future studies aiming to elucidate the mechanisms of pathologic neuronal loss occurring as the result of conditions such as neurodegenerative disorders, trauma or ischemia.}, Author = {Lossi, L. and Merighi, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {review;Central Nervous System;Human;review, academic;Apoptosis;Not relevant;11 Glia;Necrosis;Animals;Support, Non-U.S. Gov't;Neurons;Autophagocytosis}, Medline = {22674165}, Month = {4}, Nlm_Id = {0370121}, Number = {5}, Organization = {Department of Veterinary Morphophysiology, University of Torino, Via Leonardo da Vinci 44, I-10095 (TO), Grugliasco, Italy. laura.lossi\@unito.it}, Pages = {287-312}, Pii = {S0301008203000510}, Pubmed = {12787572}, Title = {In vivo cellular and molecular mechanisms of neuronal apoptosis in the mammalian CNS}, Uuid = {0C760CB7-0E5F-406A-A0F9-1D0BB309CFE2}, Volume = {69}, Year = {2003}, url = {../../Volumes/Vega/Users/ackman/James/Endnotelibraries/OMEGAData/Mergheri-prog04.pdf}} @article{Lotto:2001, Abstract = {Many neurons die as the normal brain develops. How this is regulated and whether the mechanism involves neurotrophic molecules from target cells are unknown. We found that cultured neurons from a key forebrain structure, the dorsal thalamus, develop a need for survival factors including brain-derived neurotrophic factor (BDNF) from their major target, the cerebral cortex, at the age at which they innervate it. Experiments in vivo have shown that rates of dorsal thalamic cell death are reduced by increasing cortical levels of BDNF and are increased in mutant mice lacking functional BDNF receptors or thalamocortical projections; these experiments have also shown that an increase in the rates of dorsal thalamic cell death can be achieved by blocking BDNF in the cortex. We suggest that the onset of a requirement for cortex- derived neurotrophic factors initiates a competitive mechanism regulating programmed cell death among dorsal thalamic neurons.}, Author = {Lotto, R. B. and Asavaritikrai, P. and Vali, L. and Price, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurosci}, Keywords = {Prosencephalon/cytology/drug effects/embryology/*metabolism;Cells, Cultured;Gene Expression Regulation, Developmental;inhibitors/metabolism/pharmacology;Cell Survival/drug effects/genetics;Animal;Brain-Derived Neurotrophic Factor/antagonists &;Nerve Growth Factors/antagonists &inhibitors/*metabolism/pharmacology;Culture Media, Conditioned/pharmacology;Receptor, trkB/deficiency/genetics;Receptor, trkC/deficiency/genetics;In Situ Nick-End Labeling;Apoptosis/drug effects/genetics;Neurons/cytology/drug effects/*metabolism;C;Homeodomain Proteins/genetics/metabolism;04 Adult neurogenesis factors;Mice, Knockout;Mice;Thalamic Nuclei/cytology/embryology/metabolism;Neural Pathways/cytology/embryology/metabolism;Thalamus/cytology/drug effects/embryology/metabolism;Receptors, Nerve Growth Factor/deficiency/genetics/metabolism;Cerebral Cortex/cytology/metabolism;Antibodies/pharmacology;Support, Non-U.S. Gov't}, Number = {11}, Organization = {Genes and Development Group, Department of Biomedical Sciences, University Medical School, Edinburgh EH8 9XD, United Kingdom.}, Pages = {3904-10.}, Title = {Target-derived neurotrophic factors regulate the death of developing forebrain neurons after a change in their trophic requirements}, Uuid = {CFE36093-28E5-429C-8A6C-7868412D9BC7}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11356878%20http://www.jneurosci.org/cgi/content/full/21/11/3904%20http://www.jneurosci.org/cgi/content/abstract/21/11/3904}} @article{Loturco:2006, Abstract = {The genetic basis is now known for several disorders of neuronal migration in the developing cerebral cortex. Identification of the cellular processes mediated by the implicated genes is revealing crucial stages of neuronal migration and has the potential to reveal common cellular causes of neuronal migration disorders. We hypothesize that a newly recognized morphological stage of neuronal migration, the multipolar stage, is vulnerable and is disrupted in several disorders of neocortical development. The multipolar stage occurs as bipolar progenitor cells become radially migrating neurons. Several studies using in utero electroporation and RNAi have revealed that transition out of the multipolar stage depends on the function of filamin A, LIS1 and DCX. Mutations in the genes encoding these proteins in humans cause distinct neuronal migration disorders, including periventricular nodular heterotopia, subcortical band heterotopia and lissencephaly. The multipolar stage therefore seems to be a critical point of migration control and a vulnerable target for disruption of neocortical development. This review is part of the INMED/TINS special issue Nature and nurture in brain development and neurological disorders, based on presentations at the annual INMED/TINS symposium ().}, Author = {Loturco, and Bai,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Models, Biological;Cell Movement;review;10 Development;Neuropeptides;Animals;Microtubule-Associated Proteins;Cerebral Cortex;Nervous System Malformations;Neurons}, Month = {5}, Nlm_Id = {7808616}, Number = {7}, Organization = {Department of Physiology and Neurobiology, 75 North Eagleville Road U-3156, University of Connecticut, Storrs, CT 06269, USA.}, Pages = {407-13}, Pii = {S0166-2236(06)00094-4}, Pubmed = {16713637}, Title = {The multipolar stage and disruptions in neuronal migration}, Uuid = {5683478F-1346-40C7-9AF2-806433546ED4}, Volume = {29}, Year = {2006}, url = {papers/Loturco_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.05.006}} @article{Louissaint:2002, Abstract = {Neurogenesis proceeds throughout life in the higher vocal center (HVC) of the adult songbird neostriatum. Testosterone induces neuronal addition and endothelial division in HVC. We asked if testosterone-induced angiogenesis might contribute importantly to HVC neuronal recruitment. Testosterone upregulated both VEGF and its endothelial receptor, VEGF-R2/Quek1/KDR, in HVC. This yielded a burst in local HVC angiogenesis. FACS-isolated HVC endothelial cells produced BDNF in a testosterone-dependent manner. In vivo, HVC BDNF rose by the third week after testosterone, lagging by over a week the rise in VEGF and VEGF-R2. In situ hybridization revealed that much of this induced BDNF mRNA was endothelial. In vivo, both angiogenesis and neuronal addition to HVC were substantially diminished by inhibition of VEGF-R2 tyrosine kinase. These findings suggest a causal interaction between testosterone-induced angiogenesis and neurogenesis in the adult forebrain. 0896-6273 Journal Article}, Author = {Louissaint, A. and Rao, S. and Leventhal, C. and Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Neovascularization, Physiologic;Cell Movement/drug effects/physiology;Male;Receptors, Growth Factor;Vascular Endothelial Growth Factor A;Endothelial Growth Factors/biosynthesis;Receptors, Vascular Endothelial Growth Factor;Brain;Cells, Cultured;Canaries;Animals;Endothelium, Vascular/cytology/drug effects/*physiology/secretion;Brain/*blood supply/cytology/drug effects/*growth &development;03 Adult neurogenesis progenitor source;Research Support, U.S. Gov't, P.H.S.;Cell Movement;Estrogens/pharmacology;Signal Transduction;Brain-Derived Neurotrophic Factor/biosynthesis/secretion;Cell Division;Estrogens;Receptors, Growth Factor/biosynthesis;Testosterone;Signal Transduction/drug effects/physiology;Endothelial Growth Factors;Receptor Protein-Tyrosine Kinases;Support, U.S. Gov't, P.H.S.;Brain-Derived Neurotrophic Factor;Receptor Protein-Tyrosine Kinases/biosynthesis;Neurons/*cytology/drug effects/physiology;Lymphokines;Cell Division/drug effects/physiology;Canaries/*physiology;02 Adult neurogenesis migration;Lymphokines/biosynthesis;Female;Testosterone/pharmacology;Endothelium, Vascular;BB abstr;Support, Non-U.S. Gov't;Research Support, Non-U.S. Gov't;Neurons;Neovascularization, Physiologic/drug effects/*physiology;Vascular Endothelial Growth Factors}, Medline = {22082306}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Neurology and Neuroscience, Cornell University Medical Center, 1300 York Avenue, New York, NY 10021, USA.}, Pages = {945-60}, Pii = {S0896627302007225}, Pubmed = {12086642}, Title = {Coordinated interaction of neurogenesis and angiogenesis in the adult songbird brain}, Uuid = {1B0C3BC1-B21F-4EB4-A12C-C503D3608B1D}, Volume = {34}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12086642}} @article{Lovelace:2007, Abstract = {Cell culture analyses of growth, morphology and apoptosis commonly require counting of different cell types stained with antibodies to discriminate between them. Previously, we reported the use of l-Leucine methyl ester (l-LME) to prepare purified cultures of type 1 astrocytes with minimal microglia, and staining by GFAP and CD antibodies, respectively. Here, we demonstrate a novel use of acridine orange (AO) for rapid discrimination between these cell types using fluorescence microscopy. AO accumulates in the lysosomes and also binds strongly to nuclear DNA and cytoplasmic/nucleolar RNA. Microglia may contain abundant lysosomes due to known roles in homeostasis and immune response. AO staining of lysosomes was tested at a range of concentrations, and 2.5 microg/mL was most suitable. In agreement with previous reports, microglia treated with AO showed very intense yellow, orange or red granular cytoplasmic staining of lysosomes. Microglia contain a substantially higher number of lysosomes than astrocytes, which have a variable amount. We measured the microglia population at 5.14+/-0.50\%in mixed cultures. Thus, these results show AO is a novel discriminatory marker, as microglia were easily observed and counted in clumps on top of the monolayer of astrocytes, providing a rapid alternative to time-consuming and costly antibody-based assays.}, Author = {Lovelace, Michael D. and Cahill, David M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {research support, non-u.s. gov't;11 Glia;24 Pubmed search results 2008;23 Technique}, Month = {9}, Nlm_Id = {7905558}, Number = {2}, Organization = {School of Life and Environmental Sciences, Deakin University, Pigdons Road, Waurn Ponds, Victoria 3217, Australia.}, Pages = {223-9}, Pii = {S0165-0270(07)00277-4}, Pubmed = {17662460}, Title = {A rapid cell counting method utilising acridine orange as a novel discriminating marker for both cultured astrocytes and microglia}, Uuid = {6036F8F8-B5DF-49B9-B65A-B7267D6F7217}, Volume = {165}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2007.06.009}} @article{Lovell-Badge:2001, Abstract = {Stem cells have offered much hope by promising to greatly extend the numbers and range of patients who could benefit from transplants, and to provide cell replacement therapy to treat debilitating diseases such as diabetes, Parkinson's and Huntington's disease. The issue of stem cell research is politically charged, prompting biologists to begin engaging in ethical debates, and generating in the general public an unusually high level of interest in this aspect of biology. But excitement notwithstanding, there is a long way to go in basic research before new therapies will be established, and now the pressure is on for scientists and clinicians to deliver. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Lovell-Badge, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Nature}, Keywords = {F abstr;Embryo/cytology;10 Development;Forecasting;Human;Research/trends;*Stem Cells;Politics;Animals}, Number = {6859}, Organization = {Division of Developmental Genetics, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK. rlovell\@nimr.mrc.ac.uk}, Pages = {88-91}, Pubmed = {11689952}, Title = {The future for stem cell research}, Uuid = {6958CACC-5F89-4FFC-8968-AB56C3B507F9}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689952}} @article{Lowy:1971, Author = {Lowy, D. R. and Rowe, W. P. and Teich, N. and Hartley, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {15 ERVs retroelements;Animals;Mice;Ultraviolet Rays;24 Pubmed search results 2008;Virus Replication;Cell Line;15 Retrovirus mechanism;Fluorescent Antibody Technique;Cells, Cultured;Idoxuridine;Bromodeoxyuridine;Antigens, Viral;Leukemia Virus, Murine}, Medline = {72042138}, Month = {10}, Nlm_Id = {0404511}, Number = {5}, Pages = {155-6}, Pubmed = {4330367}, Title = {Murine leukemia virus: high-frequency activation in vitro by 5-iododeoxyuridine and 5-bromodeoxyuridine}, Uuid = {719139FF-8E99-4AF4-8D07-F46A25FE65D6}, Volume = {174}, Year = {1971}} @article{Lopez-Bendito:2008, Abstract = {Functioning of the cerebral cortex requires the coordinated assembly of circuits involving glutamatergic projection neurons and GABAergic interneurons. Although much is known about the migration of interneurons from the subpallium to the cortex, our understanding of the mechanisms controlling their precise integration within the cortex is still limited. Here, we have investigated in detail the behavior of GABAergic interneurons as they first enter the developing cortex by using time-lapse videomicroscopy, slice culture, and in utero experimental manipulations and analysis of mouse mutants. We found that interneurons actively avoid the cortical plate for a period of approximately 48 h after reaching the pallium; during this time, interneurons disperse tangentially through the marginal and subventricular zones. Perturbation of CXCL12/CXCR4 signaling causes premature cortical plate invasion by cortical interneurons and, in the long term, disrupts their laminar and regional distribution. These results suggest that regulation of cortical plate invasion by GABAergic interneurons is a key event in cortical development, because it directly influences the coordinated formation of appropriate glutamatergic and GABAergic neuronal assemblies.}, Author = {L{\'o}pez-Bendito, Guillermina and S{\'a}nchez-Alca\~{n}iz, Juan Antonio and Pla, Ram{\'o}n and Borrell, V{\'\i}ctor and Pic{\'o}, Esther and Valdeolmillos, Miguel and Mar{\'\i}n, Oscar}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;10 Development;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8102140}, Number = {7}, Organization = {Instituto de Neurociencias de Alicante, Consejo Superior de Investigaciones Cient{\'\i}ficas and Universidad Miguel Hern{\'a}ndez, 03550 Sant Joan d'Alacant, Spain.}, Pages = {1613-24}, Pii = {28/7/1613}, Pubmed = {18272682}, Title = {Chemokine signaling controls intracortical migration and final distribution of GABAergic interneurons}, Uuid = {78197D19-A3AC-45A4-B9A7-D533104D7936}, Volume = {28}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4651-07.2008}} @article{Loscher:1996, Abstract = {In epilepsy research, there is growing interest in the role of the piriform cortex (PC) in the development and maintenance of limbic kindling and other types of limbic epileptogenesis leading to complex partial seizures, i.e. the most common type of seizures in human epilepsy. The PC ("primary olfactory cortex") is the largest area of the mammalian olfactory cortex and receives direct projections from the olfactory bulb via the lateral olfactory tract (LOT). Beside the obvious involvement in olfactory perception and discrimination, the PC, because of its unique intrinsic associative fiber system and its various connections to and from other limbic nuclei, has been implicated in the study of memory processing, spread of excitatory waves, and in the study of brain disorders such as epilepsy with particular emphasis on the kindling model of temporal lobe epilepsy with complex partial seizures. The interest in the kindling model is based primarily on the following observations. (1) The PC contains the most susceptible neural circuits of all forebrain regions for electrical (or chemical) induction of limbic seizures. (2) During electrical stimulation of other limbic brain regions, broad and large afterdischarges can be observed in the ipsilateral PC, indicating that the PC is activated early during the kindling process. (3) The interictal discharge, which many consider to be the hallmark of epilepsy, originates in the PC, independent of which structure serves as the kindled focus. (4) Autoradiographic studies of cerebral metabolism in rat amygdala kindling show that, during focal seizures, the area which exhibits the most consistent increase in glucose utilization is the ipsilateral paleocortex, particularly the PC. (5) During the commonly short initial afterdischarges induced by stimulation of the amygdala at the early stages of kindling, the PC is the first region that exhibits induction of immediate-early genes, such as c-fos. (6) The PC is the most sensitive brain structure to brain damage by continuous or frequent stimulation of the amygdala or hippocampus. (7) Amygdala kindling leads to a circumscribed loss of GABAergic neurons in the ipsilateral PC, which is likely to explain the increase in excitability of PC pyramidal neurons during kindling. (8) Kindling of the amygdala or hippocampus induces astrogliosis in the PC, indicating neuronal death in this brain region. Furthermore, activation of microglia is seen in the PC after amygdala kindling. (9) Complete bilateral lesions of the PC block the generalization of seizures upon kindling from the hippocampus or olfactory bulb. Incomplete or unilateral lesions are less effective in this regard, but large unilateral lesions of the PC and adjacent endopiriform nucleus markedly increase the threshold for induction of focal seizures from stimulation of the basolateral amygdala (BLA) prior to and after kindling, indicating that the PC critically contributes to regulation of excitability in the amygdala. (10) Potentiation of GABAergic neurotransmission in the PC markedly increases the threshold for induction of kindled seizures via stimulation of the BLA, again indicating a critical role of the PC in regulation of seizure susceptibility of the amygdala. Microinjections of NMDA antagonists or sodium channel blockers into the PC block seizure generalization during kindling development. (11) Neurophysiological studies on the amygdala-PC slice preparation from kindled rats showed that kindling of the amygdala induces long-lasting changes in synaptic efficacy in the ipsilateral PC, including spontaneous discharges and enhanced susceptibility to evoked burst responses. The epileptiform potentials in PC slice preparations from kindled rats seem to originate in neuron at the deep boundary of PC. Spontaneous firing and enhanced excitability of PC neurons in response to kindling from other sites is also seen in vivo, substantiating the fact that kindling induces long-lasting changes in the PC c}, Author = {L{\"o}scher, W. and Ebert, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {Epilepsy;21 Epilepsy;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Kindling (Neurology);Humans;Animals;Cerebral Cortex;review;24 Pubmed search results 2008}, Medline = {97168205}, Month = {12}, Nlm_Id = {0370121}, Number = {5-6}, Organization = {Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, Hannover, Germany.}, Pages = {427-81}, Pubmed = {9015822}, Title = {The role of the piriform cortex in kindling}, Uuid = {45CEB394-3EFE-4CE7-9AEC-7AE86BCEB44B}, Volume = {50}, Year = {1996}} @article{Lower:1996, Abstract = {Human endogenous retroviruses (HERVs) are very likely footprints of ancient germ-cell infections. HERV sequences encompass about 1\%of the human genome. HERVs have retained the potential of other retroelements to retrotranspose and thus to change genomic structure and function. The genomes of almost all HERV families are highly defective. Recent progress has allowed the identification of the biologically most active family, HTDV/HERV-K, which codes for viral proteins and particles and is highly expressed in germ-cell tumors. The demonstrable and potential roles of HTDV/HERV-K as well as of other human elements in disease and in maintaining genome plasticity are illustrated.}, Author = {L{\"o}wer, R. and L{\"o}wer, J. and Kurth, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {15 ERVs retroelements;Research Support, Non-U.S. Gov't;RNA-Directed DNA Polymerase;Female;Retroviridae;Genome, Human;HIV Seropositivity;Neoplasms;15 Retrovirus mechanism;Antibody Formation;Humans;Male;24 Pubmed search results 2008;Retroelements;review}, Medline = {96224256}, Month = {5}, Nlm_Id = {7505876}, Number = {11}, Organization = {Paul-Ehrlich-Institut, Langen, Germany.}, Pages = {5177-84}, Pubmed = {8643549}, Title = {The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences}, Uuid = {F67A3B32-EE53-11DA-8605-000D9346EC2A}, Volume = {93}, Year = {1996}} @article{Lu:2002a, Abstract = {The oligodendrocyte lineage genes Olig1 and Olig2 encode related bHLH proteins that are coexpressed in neural progenitors. Targeted disruption of these two genes sheds light on the ontogeny of oligodendroglia and genetic requirements for their development from multipotent CNS progenitors. Olig2 is required for oligodendrocyte and motor neuron specification in the spinal cord. Olig1 has roles in development and maturation of oligodendrocytes, evident especially within the brain. Both Olig genes contribute to neural pattern formation. Neither Olig gene is required for astrocytes. These findings, together with fate mapping analysis of Olig-expressing cells, indicate that oligodendrocytes are derived from Olig-specified progenitors that give rise also to neurons. 0092-8674 Journal Article}, Author = {Lu, Q. R. and Sun, T. and Zhu, Z. and Ma, N. and Garcia, M. and Stiles, C. D. and Rowitch, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Cell}, Keywords = {Nerve Tissue Proteins/*deficiency/genetics/metabolism;Animals;Female;G abstr;11 Glia;Male;Body Patterning/genetics;Stem Cells/cytology/*metabolism;Motor Neurons/cytology/*metabolism;Astrocytes/cytology/metabolism;Rhombencephalon/cytology/embryology/metabolism;Oligodendroglia/cytology/*metabolism;Mutation/physiology;Cell Lineage/*genetics;Spinal Cord/cytology/*embryology/metabolism;Support, U.S. Gov't, P.H.S.;Cell Differentiation/*genetics;Mice;Mice, Knockout;Support, Non-U.S. Gov't}, Number = {1}, Organization = {Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.}, Pages = {75-86}, Pubmed = {11955448}, Title = {Common developmental requirement for Olig function indicates a motor neuron/oligodendrocyte connection}, Uuid = {BFF5EB76-41A4-4135-A11F-43985E82E4A8}, Volume = {109}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11955448}} @article{Lu:2005, Author = {Lu, P. and Tuszynski, M. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Month = {6}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Neurosciences, University of California at San Diego, La Jolla, CA 92093-0626, USA.}, Pages = {273-8}, Pii = {S0014-4886(05)00052-X}, Pubmed = {15869931}, Title = {Can bone marrow-derived stem cells differentiate into functional neurons?}, Uuid = {2A74E8D9-D3A7-11D9-A0E9-000D9346EC2A}, Volume = {193}, Year = {2005}, url = {papers/Lu_ExpNeurol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2005.01.031}} @article{Lu:2006, Abstract = {Periventricular heterotopia (PH) is a malformation of cortical development characterized by nodules of neurons, ectopically located along the lateral ventricles of the brain. Mutations in the vesicle transport ADP-ribosylation factor guanine exchange factor 2 gene (ARFGEF2) or the actin-binding Filamin A (FLNA) gene cause PH. Previous studies have shown that FLNA expression is developmentally regulated, with strongest expression observed along the ventricular zone (VZ) and to a lesser degree in postmitotic neurons in the cortex. Here we characterize the expression patterns for ARFGEF2 within the central nervous systems of human and mouse in order to better understand their potential roles in causing PH. ARFGEF2 mRNA was widely expressed in all cortical layers, especially in the neural precursors of the ventricular and subventricular zones (SVZ) during development, with persistent but diminished expression in adulthood. ARFGEF2 encodes for the protein brefeldin-inhibited guanine exchange factor 2 (BIG2). BIG2 protein immunoreactivity was most strongly localized to the neural progenitors along the neuroependymal lining of the VZ during development, with decreased expression in adulthood. Furthermore, overlapping BIG2 and FLNA expression was greatest in these same neuroependymal cells of human embryonic brain and was co-expressed in progenitors by Western blot. Finally, transfection of a dominant-negative construct of ARFGEF2 in SHSY5Y neuroblastoma cells partially blocked FLNA transport from the Golgi apparatus to the cell membrane. These results suggest that mutations in ARFGEF2 may impair targeted transport of FLNA to the cell surface within neural progenitors along the neuroependyma and that disruption of these cells could contribute to PH formation.}, Author = {Lu, Jie and Tiao, Grace and Folkerth, Rebecca and Hecht, Jonathon and Walsh, Christopher and Sheen, Volney}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Tissue Distribution;Animals;Humans;Gene Expression Regulation, Developmental;Microfilament Proteins;21 Epilepsy;Protein Transport;Cell Movement;Mice, Inbred C57BL;RNA, Messenger;Brain Diseases;Cerebral Ventricles;Nervous System Malformations;Cerebral Cortex;21 Neurophysiology;Neurons;Ependyma;Mice;24 Pubmed search results 2008;Contractile Proteins;Stem Cells;Choristoma;Guanine Nucleotide Exchange Factors}, Month = {1}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {476-84}, Pubmed = {16320251}, Title = {Overlapping expression of ARFGEF2 and Filamin A in the neuroependymal lining of the lateral ventricles: insights into the cause of periventricular heterotopia}, Uuid = {33F04A72-67F9-4827-96F0-C62358A22C77}, Volume = {494}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20806}} @article{Lu:2006a, Abstract = {Cortical maps are remarkably precise, with organized arrays of thalamocortical afferents (TCAs) that project into distinct neuronal modules. Here, we present evidence for the involvement of efficient neurotransmitter release in mouse cortical barrel map development using barrelless mice, a loss-of-function mutant of calcium/calmodulin-activated adenylyl cyclase I (AC1), and mice with a mutation in Rab3-interacting molecule 1alpha (RIM1alpha), an active zone protein that regulates neurotransmitter release. We demonstrate that release efficacy is substantially decreased in barrelless TCAs. We identify RIMs as important phosphorylation targets for AC1 in the presynaptic terminal. We further show that RIM1alpha mutant mice have reduced TCA neurotransmitter release efficacy and barrel map deficits, although not as severe as those found in barrelless mice. This supports the role of RIM proteins in mediating, in part, AC1 signaling in barrel map development. Finally, we present a model to show how inadequacies in presynaptic function can interfere with activity-dependent processes in neuronal circuit formation. These results demonstrate how efficient synaptic transmission mediated by AC1 function contributes to the development of cortical barrel maps.}, Author = {Lu, Hui-Chen C. and Butts, Daniel A. and Kaeser, Pascal S. and She, Wei-Chi C. and Janz, Roger and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Models, Neurological;24 Pubmed search results 2008;Animals;GTP-Binding Proteins;Gene Expression Regulation, Developmental;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;research support, n.i.h., extramural;Adenylate Cyclase;Electric Stimulation;Brain Mapping;Mice, Inbred C57BL;Drug Interactions;Mice, Mutant Strains;Dizocilpine Maleate;Neural Pathways;Neuronal Plasticity;Excitatory Amino Acid Agonists;Thalamus;N-Methylaspartate;comparative study;in vitro;Blotting, Western;Synapsins;Calcium;Patch-Clamp Techniques;Time Factors;Dose-Response Relationship, Drug;Neurotransmitter Agents;Animals, Newborn;research support, non-u.s. gov't;Mice, Knockout;Mice;Somatosensory Cortex;Excitatory Postsynaptic Potentials; 21 Activity-development}, Month = {3}, Nlm_Id = {8102140}, Number = {10}, Organization = {Department of Neuroscience, Program in Developmental Biology, Baylor College of Medicine, Houston, Texas 77030, USA. hclu\@bcm.tmc.edu}, Pages = {2692-703}, Pii = {26/10/2692}, Pubmed = {16525048}, Title = {Role of efficient neurotransmitter release in barrel map development}, Uuid = {1B23633E-CF41-45E4-AFE6-B59AEE7BFBE0}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3956-05.2006}} @article{Lu:2004b, Abstract = {Differentiation of stem cells toward a neuronal lineage normally involves a gradually progressive restriction in developmental potential and is regulated by a diverse set of specific and temporally precise genetic events. However, recent studies have indicated that both rodent and human bone marrow stromal cells (MSCs) can be rapidly (within minutes to hours) induced to differentiate into neurons in vitro by relatively simple chemical means (using beta-mercaptoethanol [BME] or dimethylsulfoxide [DMSO] and butylated hydroxyanisol [BHA]; Woodbury et al. [ 2000] J. Neurosci. Res. 61:364-370). The ability to transdifferentiate an easily accessible cell source into neurons could have substantial potential for promoting neural repair. We therefore explored the potential of simple chemical methods to transdifferentiate other cell types, including primary rat fibroblasts, primary human keratinocytes, HEK293 cells, rat PC-12 cells, and as positive control rat bone marrow stromal (BMS) cells. Surprisingly, all cells except for keratinocytes adopted at least partial "neuron-like" pyramidal cell morphology with fine-cellular extensions resembling neurites upon stimulation with BME or DMSO/BHA. However, time-lapse microscopy indicated that the chemical exposure of MSCs did not result in new neurite growth but rather cellular shrinkage, with retraction of the majority of existing cell extensions, leaving only few, fine neurite-like processes. To determine whether the chemically induced transdifferentiation resulted from simple cellular toxicity, MSCs were exposed to various stressors, including detergents, high-molarity sodium chloride, and extremes of pH. In all cases, cellular shrinkage and adoption of pseudoneuronal morphology were observed. Concomitantly with cellular shrinkage, apparent increases in immunolabeling for the neuronal markers NSE and NeuN were detected in the cell soma that could not be confirmed by RT-PCR. Furthermore, blockade of protein synthesis with cycloheximide did not prevent cells from adopting "neuron-like" morphology after chemical induction. Thus, morphological changes and increases in immunolabeling for certain cellular markers upon "chemical induction" of MSCs are likely the result of cellular toxicity, cell shrinkage, and changes in the cytoskeleton and do not represent regulated steps in a complicated cellular differentiation process.}, Author = {Lu, Paul and Blesch, Armin and Tuszynski, Mark H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cell Differentiation;Embryonic Induction;Stress;Animals;Keratinocytes;Rats;Humans;Dimethyl Sulfoxide;Fibroblasts;Phosphopyruvate Hydratase;Female;Neurites;Butylated Hydroxyanisole;PC12 Cells;08 Aberrant cell cycle;Rats, Inbred F344;Bone Marrow Cells;Cell Size;Mercaptoethanol;Cytoskeleton;Artifacts;Stromal Cells;Cytotoxins;Nerve Tissue Proteins}, Month = {7}, Nlm_Id = {7600111}, Number = {2}, Organization = {Department of Neurosciences, University of California, San Diego, La Jolla, California 92093, USA.}, Pages = {174-91}, Pubmed = {15211585}, Title = {Induction of bone marrow stromal cells to neurons: differentiation, transdifferentiation, or artifact?}, Uuid = {5CC5A696-1B6D-4F5F-B4EC-F2704661254D}, Volume = {77}, Year = {2004}, url = {papers/Lu_JNeurosciRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20148}} @article{Lu:2003, Abstract = {Cortical map formation requires the accurate targeting, synaptogenesis, elaboration and refinement of thalamocortical afferents. Here we demonstrate the role of Ca2+/calmodulin-activated type-I adenylyl cyclase (AC1) in regulating the strength of thalamocortical synapses through modulation of AMPA receptor (AMPAR) trafficking using barrelless mice, a mutant without AC1 activity or cortical 'barrel' maps. Barrelless synapses are stuck in an immature state that contains few functional AMPARs that are rarely silent (NMDAR-only). Long-term potentiation (LTP) and long-term depression (LTD) at thalamocortical synapses require postsynaptic protein kinase A (PKA) activity and are difficult to induce in barrelless mice, probably due to an inability to properly regulate synaptic AMPAR trafficking. Consistent with this, both the extent of PKA phosphorylation on AMPAR subunit GluR1 and the expression of surface GluR1 are reduced in barrelless neurons. These results suggest that activity-dependent mechanisms operate through an AC1/PKA signaling pathway to target some synapses for consolidation and others for elimination during barrel map formation.}, Author = {Lu, Hui-Chen C. and She, Wei-Chi C. and Plas, Daniel T. and Neumann, Paul E. and Janz, Roger and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Long-Term Potentiation;Signal Transduction;Animals;Cells, Cultured;Gene Expression Regulation, Developmental;Mice, Mutant Strains;comparative study;Protein Transport;Receptors, AMPA;Mice, Inbred C57BL;research support, non-u.s. gov't;Mice, Inbred ICR;Animals, Newborn;research support, u.s. gov't, p.h.s.;Cerebral Cortex;Membrane Potentials;Mice;24 Pubmed search results 2008;Adenylate Cyclase;Brain Mapping; 21 Activity-development}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Division of Neuroscience and Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza S-603, Houston, Texas 77030, USA. hlu\@cns.tmc.edu}, Pages = {939-47}, Pii = {nn1106}, Pubmed = {12897788}, Title = {Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development}, Uuid = {8E4F6F65-4F40-435B-ABA5-2831DE4DC139}, Volume = {6}, Year = {2003}, url = {papers/Lu_NatNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1106}} @article{Lu:2001, Abstract = {Asymmetric division is a fundamental mechanism for generating cellular diversity. In the central nervous system of Drosophila, neural progenitor cells called neuroblasts undergo asymmetric division along the apical-basal cellular axis. Neuroblasts originate from neuroepithelial cells, which are polarized along the apical-basal axis and divide symmetrically along the planar axis. The asymmetry of neuroblasts might arise from neuroblast-specific expression of the proteins required for asymmetric division. Alternatively, both neuroblasts and neuroepithelial cells could be capable of dividing asymmetrically, but in neuroepithelial cells other polarity cues might prevent asymmetric division. Here we show that by disrupting adherens junctions we can convert the symmetric epithelial division into asymmetric division. We further confirm that the adenomatous polyposis coli (APC) tumour suppressor protein is recruited to adherens junctions, and demonstrate that both APC and microtubule-associated EB1 homologues are required for the symmetric epithelial division along the planar axis. Our results indicate that neuroepithelial cells have all the necessary components to execute asymmetric division, but that this pathway is normally overridden by the planar polarity cue provided by adherens junctions.}, Author = {Lu, B. and Roegiers, F. and Jan, L. Y. and Jan, Y. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Nature}, Keywords = {10 Development;Cell Differentiation;Human;Adherens Junctions/*physiology;Neurons/*cytology;Mitotic Spindle Apparatus/physiology;Animal;Animals, Genetically Modified;Cell Polarity;Carrier Proteins/physiology;Support, Non-U.S. Gov't;Cell Division/*physiology;Cytoskeletal Proteins/physiology;Adenomatous Polyposis Coli Protein;Body Patterning/physiology;Drosophila;Support, U.S. Gov't, P.H.S.;Epithelial Cells/cytology;F}, Number = {6819}, Organization = {Howard Hughes Medical Institute and Department of Physiology, University of California at San Francisco, 94143-0725, USA.}, Pages = {522-5.}, Title = {Adherens junctions inhibit asymmetric division in the Drosophila epithelium}, Uuid = {58A987C8-8E69-45BC-B2ED-C7D3C42893C7}, Volume = {409}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11206549}} @article{Lu:2004, Abstract = {The ageing of the human brain is a cause of cognitive decline in the elderly and the major risk factor for Alzheimer's disease. The time in life when brain ageing begins is undefined. Here we show that transcriptional profiling of the human frontal cortex from individuals ranging from 26 to 106 years of age defines a set of genes with reduced expression after age 40. These genes play central roles in synaptic plasticity, vesicular transport and mitochondrial function. This is followed by induction of stress response, antioxidant and DNA repair genes. DNA damage is markedly increased in the promoters of genes with reduced expression in the aged cortex. Moreover, these gene promoters are selectively damaged by oxidative stress in cultured human neurons, and show reduced base-excision DNA repair. Thus, DNA damage may reduce the expression of selectively vulnerable genes involved in learning, memory and neuronal survival, initiating a programme of brain ageing that starts early in adult life.}, Author = {Lu, Tao and Pan, Ying and Kao, Shyan-Yuan Y. and Li, Cheng and Kohane, Isaac and Chan, Jennifer and Yankner, Bruce A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Cell Survival;Human;Gene Expression Regulation;Antioxidants;Aging;Neuronal Plasticity;Oligonucleotide Array Sequence Analysis;DNA Repair;Middle Aged;Cells, Cultured;Homeostasis;21 Neurodegenerative;Cell Line, Tumor;Calcium;08 Aberrant cell cycle;Gene Expression Profiling;Aged;Oxidative Stress;Learning;Support, Non-U.S. Gov't;Cerebral Cortex;21 Neurophysiology;Neurons;Aged, 80 and over;Adult;Support, U.S. Gov't, P.H.S.;DNA Damage;Promoter Regions (Genetics)}, Month = {6}, Nlm_Id = {0410462}, Number = {6994}, Organization = {Department of Neurology and Division of Neuroscience, The Children's Hospital and Harvard Medical School, Enders 260,300 Longwood Avenue, Boston, Massachusetts 02115, USA.}, Pages = {883-91}, Pii = {nature02661}, Pubmed = {15190254}, Title = {Gene regulation and DNA damage in the ageing human brain}, Uuid = {CB919E08-79E0-4674-B848-F6FAB15E6886}, Volume = {429}, Year = {2004}, url = {papers/Lu_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature02661}} @article{Lu:2001a, Abstract = {The regulation of NMDA receptor (NMDAR) subunit composition and expression during development is thought to control the process of thalamocortical afferent innervation, segregation, and plasticity. Thalamocortical synaptic plasticity in the mouse is dependent on NMDARs containing the NR2B subunit, which are the dominant form during the "critical period" window for plasticity. Near the end of the critical period there is a gradual increase in the contribution of NR2A subunits that happens in parallel to changes in NMDAR-mediated current kinetics. However, no extension of the critical period occurs in NR2A knockout mice, despite the fact that NMDA subunit composition and current kinetics remain immature past the end of the critical period. These data suggest that regulation of NMDAR subunit composition is not essential for closing the critical period plasticity window in mouse somatosensory barrel cortex.}, Author = {Lu, H. C. and Gonzalez, E. and Crair, M. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-27 11:35:53 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Excitatory Amino Acid Antagonists;Excitatory Postsynaptic Potentials;Long-Term Potentiation;Animals;Piperidines;Synapses;Gene Expression Regulation, Developmental;Neuronal Plasticity;Receptors, AMPA;Mice, Inbred C57BL;research support, non-u.s. gov't;Critical Period (Psychology);Thalamus;Quinoxalines;Mice, Knockout;research support, u.s. gov't, p.h.s.;Somatosensory Cortex;Mice;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Brain Mapping; 21 Activity-development}, Month = {11}, Nlm_Id = {8809320}, Number = {4}, Organization = {Division of Neuroscience and Program in Developmental Biology, One Baylor Plaza, S-603, Baylor College of Medicine, Houston, TX 77030, USA.}, Pages = {619-34}, Pii = {S0896-6273(01)00501-3}, Pubmed = {11719203}, Title = {Barrel cortex critical period plasticity is independent of changes in NMDA receptor subunit composition}, Uuid = {F7E6986F-B211-4895-8EF3-FE233D4AAE3C}, Volume = {32}, Year = {2001}} @article{Lu:2004a, Abstract = {NMDA receptor (NMDAR)-mediated increases in AMPA receptor (AMPAR) currents are associated with long-term synaptic potentiation (LTP). Here, we provide evidence that similar changes occur in response to normal increases in sensory stimulation during development. Experiments discriminated between eye opening-induced and age-dependent changes in synaptic currents. At 6 hr after eye opening (AEO), a transient population of currents mediated by NR2B-rich NMDARs increase significantly, and silent synapses peak. Sustained increases in evoked and miniature AMPAR currents occur at 12 hr AEO. Significant changes in AMPAR:NMDAR evoked current ratios, contacts per axon, and inputs per cell are present at 24 hr AEO. The AMPAR current changes are those seen in vitro during NMDAR-dependent LTP. Here, they are a consequence of eye opening and are associated with a new wave of synaptic refinement. These data also suggest that new NR2B-rich NMDAR currents precede and may initiate this developmental synaptic potentiation and functional tuning.}, Author = {Lu, Wei and Constantine-Paton, Martha}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Synapses;research support, u.s. gov't, p.h.s. ;Electric Conductivity;Rats, Sprague-Dawley;21 Neurophysiology;Superior Colliculus;Presynaptic Terminals;Neuronal Plasticity;Rats;Receptors, AMPA;Time Factors;Eyelids;Animals, Newborn;Animals;Receptors, N-Methyl-D-Aspartate;24 Pubmed search results 2008;Axons}, Month = {7}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Biology, McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge 02139, USA.}, Pages = {237-49}, Pii = {S0896627304004209}, Pubmed = {15260959}, Title = {Eye opening rapidly induces synaptic potentiation and refinement}, Uuid = {3BA8B82A-6374-4494-8DCA-A2F3889A922C}, Volume = {43}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.06.031}} @article{Lu:2002, Abstract = {We investigated the role of the CXCR4 chemokine receptor in development of the mouse hippocampus. CXCR4 mRNA is expressed at sites of neuronal and progenitor cell migration in the hippocampus at late embryonic and early postnatal ages. mRNA for stromal cell-derived factor 1 (SDF-1), the only known ligand for the CXCR4 receptor, is expressed close to these migration sites, in the meninges investing the hippocampal primordium and the primordium itself. In mice engineered to lack the CXCR4 receptor, the morphology of the hippocampal dentate gyrus (DG) is dramatically altered. Gene expression markers for DG granule neurons and bromodeoxyuridine labeling of dividing cells revealed an underlying defect in the stream of postmitotic cells and secondary dentate progenitor cells that migrate toward and form the DG. In the absence of CXCR4, the number of dividing cells in the migratory stream and in the DG itself is reduced, and neurons appear to differentiate prematurely before reaching their target. Our findings indicate a role for the SDF-1/CXCR4 chemokine signaling system in DG morphogenesis. Finally, the DG is unusual as a site of adult neurogenesis. We find that both CXCR4 and SDF-1 are expressed in the adult DG, suggesting an ongoing role in DG morphogenesis.}, Author = {Lu, Meiling and Grove, Elizabeth A. and Miller, Richard J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Receptors, CXCR4;Signal Transduction;Animals;Female;Culture Techniques;Hippocampus;Intracellular Fluid;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Mice, Knockout;Cerebral Cortex;Dentate Gyrus;Chemokines, CXC;Neurons;Mice;Cell Division;Gene Expression;Ligands;Research Support, Non-U.S. Gov't}, Medline = {22008001}, Month = {5}, Nlm_Id = {7505876}, Number = {10}, Organization = {Department of Molecular Pharmacology and Biological Chemistry, Northwestern University, Chicago, IL 60611, USA.}, Pages = {7090-5}, Pii = {092013799}, Pubmed = {11983855}, Title = {Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor}, Uuid = {241601F4-7114-11DA-9A4D-000D9346EC2A}, Volume = {99}, Year = {2002}, url = {papers/Lu_ProcNatlAcadSciUSA2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.092013799}} @article{Lubenov:2008, Abstract = {The level of synchronization in distributed systems is often controlled by the strength of the interactions between individual elements. In brain circuits the connection strengths between neurons are modified under the influence of spike-timing-dependent plasticity (STDP) rules. Here we show that when recurrent networks with conduction delays exhibit population bursts, STDP rules exert a strong decoupling force that desynchronizes activity. Conversely, when activity in the network is random, the same rules can have a coupling and synchronizing influence. The presence of these opposing forces promotes the self-organization of spontaneously active neuronal networks to a state at the border between randomness and synchrony. The decoupling force of STDP may be engaged by the synchronous bursts occurring in the hippocampus during slow-wave sleep, leading to the selective erasure of information from hippocampal circuits as memories are established in neocortical areas.}, Author = {Lubenov, Evgueniy V. and Siapas, Athanassios G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;Action Potentials;Hippocampus;Models, Neurological;Neuronal Plasticity;Rats;comparative study;Nerve Net;Animals;24 Pubmed search results 2008;Neurons}, Month = {4}, Nlm_Id = {8809320}, Number = {1}, Organization = {Division of Biology, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA 91125, USA.}, Pages = {118-31}, Pii = {S0896-6273(08)00128-1}, Pubmed = {18400168}, Title = {Decoupling through synchrony in neuronal circuits with propagation delays}, Uuid = {CA534A3F-EF8C-4426-B2A4-C19385EFA107}, Volume = {58}, Year = {2008}, url = {papers/Lubenov_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.01.036}} @article{Lucio:1997, Abstract = {Previous studies have shown that hypothyroidism modifies the development of callosal connections. In particular, adult hypothyroid rats have fewer callosally projecting neurons in layers II-III of the auditory cortex and more in layer V. This might be due to disturbance in the stabilization/elimination of juvenile callosal axons, or to abnormal neuronal migration during cortical histogenesis. To distinguish between these possibilities we have studied the distribution of callosally projecting auditory neurons at different postnatal ages using retrogradely transported tracers, and the cortical neurogenetic gradients using DNA labelling with 5-bromo-2'-deoxiuridine. In hypothyroid rats, injected at postnatal day 5 (P5) and killed at P18-20, most of the neurons retrogradely labelled from the contralateral hemisphere are distributed between layers IV and VI, as in older rats. In hypothyroid rats, many neurons are at locations inappropriate for their birthdate, including the subcortical white matter, resulting in more diffuse radial neurogenetic gradients. These results indicate that early induced hypothyroidism alters neuronal migration and prevents the establishment of callosal connections from cortical layers II-III.}, Author = {Lucio, R. A. and Garc{\'\i}a, J. V. and Ram{\'o}n Cerezo, J. and Pacheco, P. and Innocenti, G. M. and Berbel, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Auditory Cortex;Hypothyroidism;Rats;Not relevant;Rats, Wistar;11 Glia;Histocytochemistry;Disease Models, Animal;Male;Support, Non-U.S. Gov't;Animals}, Medline = {97321031}, Month = {6}, Nlm_Id = {9110718}, Number = {4}, Organization = {Departamento de Histolog{\'\i}a, Universidad de Alicante, Spain.}, Pages = {303-16}, Pubmed = {9177762}, Title = {The development of auditory callosal connections in normal and hypothyroid rats}, Uuid = {877BF3FE-AD94-4F90-883D-6B67A282FDD0}, Volume = {7}, Year = {1997}} @article{Ludwig:2003, Abstract = {Hyperpolarization-activated cation (HCN) channels are believed to be involved in the generation of cardiac pacemaker depolarizations as well as in the control of neuronal excitability and plasticity. The contributions of the four individual HCN channel isoforms (HCN1-4) to these diverse functions are not known. Here we show that HCN2-deficient mice exhibit spontaneous absence seizures. The thalamocortical relay neurons of these mice displayed a near complete loss of the HCN current, resulting in a pronounced hyperpolarizing shift of the resting membrane potential, an altered response to depolarizing inputs and an increased susceptibility for oscillations. HCN2-null mice also displayed cardiac sinus dysrhythmia, a reduction of the sinoatrial HCN current and a shift of the maximum diastolic potential to hyperpolarized values. Mice with cardiomyocyte- specific deletion of HCN2 displayed the same dysrhythmia as mice lacking HCN2 globally, indicating that the dysrhythmia is indeed caused by sinoatrial dysfunction. Our results define the physiological role of the HCN2 subunit as a major determinant of membrane resting potential that is required for regular cardiac and neuronal rhythmicity.}, Author = {Ludwig, Andreas and Budde, Thomas and Stieber, Juliane and Moosmang, Sven and Wahl, Christian and Holthoff, Knut and Langebartels, Anke and Wotjak, Carsten and Munsch, Thomas and Zong, Xiangang and Feil, Susanne and Feil, Robert and Lancel, Marike and Chien, Kenneth R. and Konnerth, Arthur and Pape, Hans-Christian C. and Biel, Martin and Hofmann, Franz}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0261-4189}, Journal = {EMBO J}, Keywords = {Neurons;Research Support, Non-U.S. Gov't;research support, non-u.s. gov't ;24 Pubmed search results 2008;Heart Rate;Male;Protein Subunits;Cerebral Cortex;Animals;Electrocardiography;Genes, Reporter;In Vitro;Motor Activity;Membrane Potentials;Ion Channels;21 Epilepsy;Thalamus;Epilepsy, Absence;Gene Targeting;Sinoatrial Node;Patch-Clamp Techniques;Mice, Knockout;21 Neurophysiology;Recombination, Genetic;Mice;Arrhythmia, Sinus;Mice, Transgenic;Muscle Proteins;in vitro ;Myocytes, Cardiac}, Medline = {22401613}, Month = {1}, Nlm_Id = {8208664}, Number = {2}, Organization = {Institut f{\"u}r Pharmakologie und Toxikologie, Technische Universit{\"a}t M{\"u}nchen, D-80802 M{\"u}nchen, Germany. ludwig\@ipt.med.tu-muenchen.de}, Pages = {216-24}, Pubmed = {12514127}, Title = {Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2}, Uuid = {233FA7C2-CB18-4F9A-B0E4-E9433A709279}, Volume = {22}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/emboj/cdg032}} @article{Ludwin:1990, Abstract = {Unilateral enucleation of the eye in adult male rats was performed in an attempt to resolve the longstanding controversy as to the nature of the phagocytic cells during Wallerian degeneration in the central nervous system. Previously both resident microglia and circulating monocytes, as well as oligodendrocytes, have all been considered to be the phagocytic cells. In these present experiments macrophages and microglia were studied using lectin histochemistry for Griffonia simplicifolia agglutinin and the monoclonal antibody ED1 at light microscopic level. Oligodendrocytes were demonstrated ultrastructurally using immunohistochemistry with monoclonal antibodies against myelin oligodendrocyte glycoprotein (MOG). Ultrastructural examination of the degeneration optic nerves confirmed longstanding reports of the slow nature of breakdown in the adult central nervous system. During the early periods of breakdown, starting at 1 week and continuing to 1 or 2 months, it was difficult to type, on ultrastructural examination alone, the nature of all the cells undergoing phagocytosis, but many of them resembled microglia/macrophages. Myelin debris cleared very slowly and could still be recognised prominently in the nerve up to 22 months post-enucleation. Lectin and immunochemical examination showed that the early major phagocytic component of phagocytosis was carried out by macrophages, probably both circulating and resident. In addition, however, myelin and axonal debris was taken up or retracted into oligodendrocyte processes, which were stained with antibodies to MOG. This oligodendrocyte component appeared to be small in relationship to the overall degree of debris.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Ludwin, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Plant Lectins;Nerve Degeneration;Animals;Phagocytosis;Macrophages;Rats;Oligodendroglia;Optic Nerve;Not relevant;11 Glia;Male;Support, Non-U.S. Gov't;Wallerian Degeneration;Histocytochemistry;Immunohistochemistry;Microscopy, Electron;Biological Markers;Lectins}, Medline = {90378936}, Nlm_Id = {0412041}, Number = {3}, Organization = {Department of Pathology, Kingston General Hospital, Ontario, Canada.}, Pages = {266-73}, Pubmed = {2399808}, Title = {Phagocytosis in the rat optic nerve following Wallerian degeneration}, Uuid = {4FE27560-3391-46A4-A693-BEA54B80DD45}, Volume = {80}, Year = {1990}} @article{Lue:2002, Abstract = {The induction of an antibody response to amyloid beta (Abeta) peptide has become a strategy for the treatment of Alzheimer's disease (AD). This has proven effective in reducing the plaque burden in transgenic mice that develop Abeta plaques similar to human AD patients. The mechanism for enhanced clearance of Abeta is partly due to the interaction of immunoglobulin Fcgamma receptor-expressing microglia and specific antibody-opsonized Abeta deposits. This interaction can stimulate Fcgamma receptor-mediated phagocytosis, but also results in inflammatory activation of these cells. Consequently, interaction of microglia with antibody-antigen complexes could exacerbate the existing inflammation in the brains of AD patients. In this study, we used substrate-bound Abeta and cultured human microglia from AD and non-demented cases to model interaction of microglia and antibody-opsonized plaques in AD brains. Enhanced production of tumor necrosis factor-alpha, macrophage colony stimulating factor, interleukin-10, and superoxide ions was detected. We also demonstrated enhanced uptake of opsonized Abeta by microglia, which was reduced significantly in the presence of excess IgG, indicative of the involvement of Fcgamma receptor-mediated mechanisms. Human microglia were shown in this study to express mRNA for Fcgamma receptors I, IIa, IIb, and III. The expression of Fcgamma receptor II was augmented by proinflammatory stimulation. These results suggest that initial interactions of human microglia with antibody-opsonized amyloid could result in increased inflammation. The consequence of this on inflammatory pathology in AD brains needs to be considered before immunization is used as a strategy for treating AD.}, Author = {Lue, Lih-Fen F. and Walker, Douglas G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Immunotherapy;Human;Phagocytosis;Cells, Cultured;Amyloid beta-Protein;Frontal Lobe;Microglia;Superoxides;Culture Media, Conditioned;Opsonins;11 Glia;RNA, Messenger;Antibodies;Support, Non-U.S. Gov't;Peptide Fragments;Alzheimer Disease;Support, U.S. Gov't, P.H.S.;Receptors, IgG;Cytokines}, Medline = {22292042}, Month = {11}, Nlm_Id = {7600111}, Number = {4}, Organization = {Sun Health Research Institute, Sun City, Arizona 85351, USA.}, Pages = {599-610}, Pubmed = {12404514}, Title = {Modeling Alzheimer's disease immune therapy mechanisms: interactions of human postmortem microglia with antibody-opsonized amyloid beta peptide}, Uuid = {9E4BC686-2CFF-48F3-B5D2-D9D9F99C636C}, Volume = {70}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10422}} @article{Luhmann:1999, Abstract = {The cellular morphology and electrophysiology of the rat neocortex between embryonic day (E) 18 and postnatal day (P) 3 was studied in vitro by extracellular biocytin injections and whole-cell recordings, respectively. Most neurons were characterized by a small number of short-range dendrites and a main axon that was directed towards the white matter. Biocytin injections into the marginal zone and the cortical plate labeled far-reaching connections extending up to 2 mm in horizontal direction, indicating the existence of a dense network of long-range intrinsic projections in the neonatal cortex. Action potentials could be elicited as early as E18 and repetitive firing could first be observed at P0. Electrical stimulation of the immature cortex at various positions elicited polyphasic and long-lasting (up to 1 s) excitatory postsynaptic potentials and currents, which were significantly reduced in amplitude by a selective N-methyl-D-aspartate receptor antagonist. Our data indicate that the perinatal cortex manifests the structural and functional conditions for powerful excitatory interactions, which increase the likelihood for the generation of epileptiform activity during this developmental period. Copyright Copyright 1999 S. Karger AG, Basel}, Author = {Luhmann, H. J. and Schubert, D. and K{\"o}tter, R. and Staiger, J. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Embryo;Synapses;Cell Membrane;Research Support, Non-U.S. Gov't;Electric Conductivity;21 Neurophysiology;21 Epilepsy;Rats;Neural Pathways;Rats, Wistar;Animals, Newborn;Synaptic Transmission;Electrophysiology;Animals;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Medline = {20044653}, Month = {11}, Nlm_Id = {7809375}, Number = {3-5}, Organization = {Institute of Neurophysiology, University of D{\"u}sseldorf, Germany. luhmann\@uni-duesseldorf.de}, Pages = {298-309}, Pii = {dne21298}, Pubmed = {10575253}, Title = {Cellular morphology and physiology of the perinatal rat cerebral cortex}, Uuid = {A9A97EC4-BFDF-4493-9378-479396D7AFEC}, Volume = {21}, Year = {1999}, url = {papers/Luhmann_DevNeurosci1999.pdf}} @article{Luhmann:1996, Abstract = {Hypoxia, ischemia and other forms of brain injury during the pre- and perinatal period may cause neuronal migration disorders which results in irreversible structural modifications. In human neocortex, these malformations have been associated with severe mental retardation, motor dysfunction and the manifestation of therapy-resistant epilepsy. We were interested in analyzing the expression of epileptiform activity in an animal model of neocortical migration disorders. Newborn rats received a focal freeze lesion and were investigated anatomically and in vitro electrophysiologically after survival times of up to five months. Anatomic abnormalities included loss of normal cortical lamination (focal microgyrus) and presence of ectopic cell clusters in layer I and in the white matter (heterotopia). The functional in vitro analyses with eight extracellular recording electrodes revealed a prominent hyperexcitability of the disorganized neocortical network. Electrical stimulation of the afferents elicited epileptiform responses that propagated over > 4 mm in the horizontal direction. In untreated and sham-operated animals, this spread of evoked activity was restricted to 0.5-1 mm. Epileptiform responses were not significantly affected by APV but blocked by NBQX, indicating that AMPA receptors play a prominent role in the generation and propagation of this pathophysiological activity. Our data suggest that the experimentally induced migration disturbances cause long-term structural and/or functional modifications in the neocortical network which may form the basis for the expression of epileptiform activity.}, Author = {Luhmann, H. J. and Raabe, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:51 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Epilepsy;24 Pubmed search results 2008;Electroencephalography;Research Support, Non-U.S. Gov't;21 Dysplasia-heterotopia;21 Neurophysiology;21 Epilepsy;Rats;Choristoma;Rats, Wistar;Animals, Newborn;Electrophysiology;Animals;Disease Models, Animal;Cerebral Cortex;Humans;Brain}, Medline = {97138664}, Month = {12}, Nlm_Id = {8703089}, Number = {1}, Organization = {Institute of Physiology II, Department of Neurophysiology, D{\"u}sseldorf, Germany. luhmann\@uni-duesseldorf.de}, Pages = {67-74}, Pii = {S0920121196000411}, Pubmed = {8985688}, Title = {Characterization of neuronal migration disorders in neocortical structures: I. Expression of epileptiform activity in an animal model}, Uuid = {F31176E4-12C6-4C35-BB05-98AB97DEEB95}, Volume = {26}, Year = {1996}, url = {papers/Luhmann_EpilepsyRes1996.pdf}} @article{Luhmann:1998, Abstract = {The majority of patients showing neuronal migration disorders in cortical structures suffer from pharmaco-resistant epilepsy. In order to study the molecular and cellular mechanisms underlying this pronounced hyperexcitability, we used an animal model of focal cortical dysplasia demonstrating structural malformations which resemble the human pathology of microgyria. Neocortical slices prepared from adult rats, which at the day of birth received a cortical freeze lesion, were analysed in vitro with an array of eight extracellular recording electrodes to investigate the pattern and pharmacology of propagating epileptiform activity in microgyric cortex. In cortical slices exhibiting neuronal migration disorders, orthodromic synaptic stimulation elicited late recurrent activity and early epileptiform responses that spread with 0.06 m/s over > or = 3.5 mm across the cortex. Application of a N-methyl-D-aspartate (NMDA) antagonist blocked the late recurrent activity, but not the propagation of the early epileptiform responses. The latter were blocked by an (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) antagonist, indicating that the spread of this activity was predominantly mediated by activation of AMPA receptors. A very similar response pattern could be observed in neocortical slices obtained from untreated age-matched control rats, when the slice was partially disinhibited by bath-application of 5 microM bicuculline methiodide. Stimulus-evoked epileptiform signals recorded in disinhibited slices propagated with 0.08 m/s across the cortex and showed the same sensitivity to ionotropic glutamate antagonists as in dysplastic cortex. Our results indicate that widespread structural and/or functional modifications of the AMPA receptor and possibly also of the gamma-amino-butyric acid type A receptor contribute to the pronounced hyperexcitability in dysplastic cortex.}, Author = {Luhmann, H. J. and Raabe, K. and Q{\"u}, M. and Zilles, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Electric Stimulation;Epilepsies, Partial;In Vitro;Evoked Potentials;Rats;Animals;Comparative Study;Electrodes;Parietal Lobe;Neocortex;Synaptic Transmission;Cell Movement;Extracellular Space;Frontal Lobe;Receptors, AMPA;Rats, Wistar;Disease Models, Animal;21 Epilepsy;Animals, Newborn;21 Neurophysiology;Neurons;Receptors, Kainic Acid;Cryosurgery;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Electroencephalography;Research Support, Non-U.S. Gov't}, Medline = {99000142}, Month = {10}, Nlm_Id = {8918110}, Number = {10}, Organization = {Institute of Neurophysiology, University of D{\"u}sseldorf, Germany. luhmann\@uni-duesseldorf.de}, Pages = {3085-94}, Pubmed = {9786203}, Title = {Characterization of neuronal migration disorders in neocortical structures: extracellular in vitro recordings}, Uuid = {79EE6F9E-013D-11DB-9E68-000D9346EC2A}, Volume = {10}, Year = {1998}} @article{Luhmann:2000, Abstract = {We examined the generation, propagation and pharmacology of 4-aminopyridine (4-AP)-induced epileptiform activity (EA) in the intact interconnected limbic structure of the newborn (P0-7) rat in vitro. Whole-cell recordings of CA3 pyramidal cells and multisite field potential recordings in CA3, CA1, dentate gyrus, and lateral and medial entorhinal cortex revealed 4-AP-induced EA as early as P0-1. At this age, EA was initiated in the CA3 region and propagated to CA1, but not to the entorhinal cortex. Starting from P3-4, EA propagated from CA3 to the entorhinal cortex. Along the CA3 septo-temporal axis, EA arose predominantly from the septal pole and spread towards the temporal site. Whereas the onset of 4-AP-induced EA decreased with age from 21.2 +/- 1.6 min at P0-1 to 4.7 +/- 0.63 min at P6-7, the seizure duration increased in the same age groups from 98 +/- 14 s to 269.4 +/- 85.9 s, respectively. The EA was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not by DL-2-amino-5-phosphonovaleric acid (APV), (+)-MK-801 hydrogen maleate (MK-801) or (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG), suggesting that they were mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor activation. We conclude that: (i) the septal pole of the hippocampal CA3 region plays a central role in the generation of EA in the neonatal limbic system; and (ii) AMPA/kainate receptor-mediated EA can be generated in CA3 already at birth. Therefore, the recurrent collateral synapses and circuits required for the generation of EA are developed earlier than previously suggested on the basis of studies on hippocampal slices.}, Author = {Luhmann, H. J. and Dzhala, V. I. and Ben-Ari, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Receptors, Glutamate;Animals;In Vitro;Rats;Dizocilpine Maleate;21 Epilepsy;Patch-Clamp Techniques;Epilepsy;2-Amino-5-phosphonovalerate;Hippocampus;Rats, Wistar;Entorhinal Cortex;Benzoates;Animals, Newborn;Glycine;Action Potentials;Neurons;21 Neurophysiology;Age Factors;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;4-Aminopyridine;Research Support, Non-U.S. Gov't}, Medline = {20428258}, Month = {8}, Nlm_Id = {8918110}, Number = {8}, Organization = {Institute of Neurophysiology, University of Duesseldorf, POB 101007, D-40001 Duesseldorf, Germany. luhmann\@uni-duesseldorf.de}, Pages = {2757-68}, Pii = {ejn156}, Pubmed = {10971618}, Title = {Generation and propagation of 4-AP-induced epileptiform activity in neonatal intact limbic structures in vitro}, Uuid = {B79AF588-F92A-4DB4-98BD-E452A77445C1}, Volume = {12}, Year = {2000}} @article{Luhmann:1998a, Abstract = {Neuronal migration disorders (NMD) are involved in a variety of different developmental disturbances and in therapy-resistant epilepsy. The cellular mechanisms underlying the pronounced hyperexcitability in dysplastic cortex are not well understood and demand further clinical and experimental analyses. We used a focal freeze-lesion model in cerebral cortex of newborn rats to study the functional consequences of NMD. Intracellular recordings from supragranular regular spiking cells in cortical slices from adult sham-operated rats revealed normal passive and active intrinsic membrane properties and normal stimulus-evoked excitatory and inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively). Regular spiking neurons recorded in rat dysplastic cortex showed on average a significantly smaller action potential amplitude, a slower spike rise, and a less steep primary frequency-current relationship. Stimulus-elicited EPSPs in NMD-affected cortex consisted of multiphasic burst discharges, which coincided with extracellular field potentials and lasted 150-800 ms. These epileptiform responses could be recorded at membrane potentials between -50 and -110 mV and were blocked by -2-amino-5-phosphonovaleric acid (APV), indicating the involvement of N-methyl--aspartate (NMDA) receptors. Isolated NMDA-mediated and APV-sensitive EPSPs could be recorded at membrane potentials negative to -70 mV, suggesting that NMDA receptors are activated at relatively negative membrane potentials. In comparison with the controls, polysynaptic IPSPs mediated by the gamma-aminobutyric acid (GABA) type A and B receptor were either absent or reduced in peak conductance in microgyric cortex by 27\%(P < 0.05) and 17\%, respectively. However, monosynaptic IPSPs recorded in the presence of ionotropic glutamate receptor antagonists revealed a similar efficacy in NMD and control cortex, indicating that GABAergic neurons in microgyric cortex get a weaker excitatory input. Our data indicate that the expression of epileptiform activity in NMD-affected cortex rather results from an imbalance between excitatory and inhibitory synaptic transmission than from alterations in the intrinsic membrane properties. This imbalance is caused by an increase in NMDA-receptor-mediated excitation in pyramidal neurons and a concurrent decrease of glutamatergic input onto inhibitory interneurons.}, Author = {Luhmann, H. J. and Karpuk, N. and Q{\"u}, M. and Zilles, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Excitatory Amino Acid Antagonists;Excitatory Postsynaptic Potentials;Animals;Synapses;In Vitro;Aging;Rats;Evoked Potentials;Synaptic Transmission;Neocortex;21 Epilepsy;2-Amino-5-phosphonovalerate;Cell Movement;Pyramidal Cells;Rats, Wistar;Brain Diseases;Animals, Newborn;Quinoxalines;21 Neurophysiology;Neurons;Membrane Potentials;Interneurons;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Research Support, Non-U.S. Gov't}, Medline = {98325103}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Institute of Neurophysiology, University of D{\"u}sseldorf, D-40001 Dusseldorf, Germany.}, Pages = {92-102}, Pubmed = {9658031}, Title = {Characterization of neuronal migration disorders in neocortical structures. II. Intracellular in vitro recordings}, Uuid = {5CDA474E-79F8-4C02-B955-402E89679F9E}, Volume = {80}, Year = {1998}} @article{Lujan:2005, Abstract = {Our understanding of the role played by neurotransmitter receptors in the developing brain has advanced in recent years. The major excitatory and inhibitory neurotransmitters in the brain, glutamate and GABA, activate both ionotropic (ligand-gated ion channels) and metabotropic (G protein-coupled) receptors, and are generally associated with neuronal communication in the mature brain. However, before the emergence of their role in neurotransmission in adulthood, they also act to influence earlier developmental events, some of which occur prior to synapse formation: such as proliferation, migration, differentiation or survival processes during neural development. To fulfill these actions in the constructing of the nervous system, different types of glutamate and GABA receptors need to be expressed both at the right time and at the right place. The identification by molecular cloning of 16 ionotropic glutamate receptor subunits, eight metabotropic glutamate receptor subtypes, 21 ionotropic and two metabotropic GABA receptor subunits, some of which exist in alternatively splice variants, has enriched our appreciation of how molecular diversity leads to functional diversity in the brain. It now appears that many different types of glutamate and GABA receptor subunits have prominent expression in the embryonic and/or postnatal brain, whereas others are mainly present in the adult brain. Although the significance of this differential expression of subunits is not fully understood, it appears that the change in subunit composition is essential for normal development in particular brain regions. This review focuses on emerging information relating to the expression and role of glutamatergic and GABAergic neurotransmitter receptors during prenatal and postnatal development.}, Author = {Luj{\'a}n, R. and Shigemoto, R. and L{\'o}pez-Bendito, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Humans;Neurons;Cell Differentiation;research support, non-u.s. gov't;Synapses;21 Neurophysiology;24 Pubmed search results 2008;Cell Proliferation;Signal Transduction;21 Activity-development;Receptors, GABA;Receptors, Neurotransmitter;Animals;Brain;Cell Movement;review;Glutamic Acid}, Nlm_Id = {7605074}, Number = {3}, Organization = {Facultad de Medicina and Centro Regional de Investigaciones Biom{\'e}dicas, Universidad de Castilla-La Mancha, Campus Biosanitario, Avda. de Almansa s/n, 02006 Albacete, Spain. rlujan\@med-ab.uclm.es}, Pages = {567-80}, Pii = {S0306-4522(04)00872-3}, Pubmed = {15590141}, Title = {Glutamate and GABA receptor signalling in the developing brain}, Uuid = {0134439A-87A9-4F1F-834D-E5F3807DD6A2}, Volume = {130}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2004.09.042}} @article{Lundberg:2001, Abstract = {The hormone leptin has been shown to be an afferent signal in a negative-feedback loop regulating body weight, and consequently, the administration of the gene product for the treatment of obesity has recently attracted considerable attention. Leptin is produced by adipocytes in response to increased trigyceride storage, and appears to affect body weight primarily through target cells in the hypothalamus. Although plasma levels of leptin correlate positively with adipose tissue mass in normal humans and animals, recent studies have shown that obese humans and animals appear to be relatively resistant to the increased plasma levels of leptin. Analysis of the levels of leptin in the cerebrospinal fluid suggests that the uptake of leptin across the blood-brain barrier may be saturable. Taken together, these results suggest that therapeutic approaches to deliver leptin through the circulation may prove to be problematic. Although recent clinical trials have suggested that peripherally administered leptin might lead to a reduction in body weight in humans, it is likely that the more effective delivery of leptin to cellular targets within the central nervous system will be necessary in order to fully reveal the therapeutic potential of the gene product. In an effort to provide a means for the delivery of leptin that obviates the need for the gene product to traverse the blood-brain barrier, we have evaluated the use of recombinant adeno-associated vectors to deliver leptin intraventricularly or directly to the hypothalamus.}, Author = {Lundberg, C. and Jungles, S. J. and Mulligan, R. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {Obesity;Animals;Humans;Leptin;Dependovirus;Brain;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Mice, Obese;Genetic Vectors;Cerebral Ventricles;Weight Loss;Hypothalamus;Gene Therapy;Muscle, Skeletal;Recombination, Genetic;Mice;Luminescent Proteins;Genes, Reporter;Research Support, Non-U.S. Gov't}, Medline = {21110318}, Month = {2}, Nlm_Id = {9604648}, Number = {2}, Organization = {Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {169-72}, Pubmed = {11175734}, Title = {Direct delivery of leptin to the hypothalamus using recombinant adeno-associated virus vectors results in increased therapeutic efficacy}, Uuid = {1FF33080-C024-4893-B947-6725A443186C}, Volume = {19}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/84448}} @article{Lunyak:2005, Abstract = {Epigenetic strategies control the orderly acquisition and maintenance of neuronal traits. A complex network of transcriptional repressors and co-repressors mediates gene specificity for these strategies. In this issue of Cell, a study by Ballas and coworkers (Ballas et al., 2005) provides insight into the early lineage commitment events during neurogenesis. This study demonstrates that regulation of the REST/NRSF transcriptional repressor plays a fundamental role in the progression of pluripotent cells to lineage-restricted neural progenitors.}, Author = {Lunyak, Victoria V. and Rosenfeld, Michael G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Epigenesis, Genetic;Neurons;Cell Differentiation;Gene Expression Regulation, Developmental;review;Repressor Proteins;24 Pubmed search results 2008;review, tutorial;comment;Nervous System;Animals;Humans;Pluripotent Stem Cells;Cell Lineage;Transcription Factors}, Month = {5}, Nlm_Id = {0413066}, Number = {4}, Pages = {499-501}, Pii = {S0092-8674(05)00445-9}, Pubmed = {15907461}, Title = {No rest for REST: REST/NRSF regulation of neurogenesis}, Uuid = {3DFD3A04-9CC5-444C-AAB5-2DE80275068C}, Volume = {121}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.05.003}} @article{Luo:2006, Abstract = {In the adult mouse brain, the subventricular zone (SVZ) is a neurogenic stem cell niche only 4-5 cell diameters thick. Within this narrow zone, a unique microenvironment supports stem cell self-renewal, gliogenesis or neurogenesis lineage decisions and tangential migration of newly generated neurons out of the SVZ and into the olfactory bulb. However, with aging, SVZ neurogenesis declines. Here, we examine the dynamic interplay between SVZ cytoarchitecture and neurogenesis through aging. Assembly of high-resolution electron microscopy images of corresponding coronal sections from 2-, 10- and 22-month-old mice into photomontages reveal a thinning of the SVZ with age. Following a 2-h BrdU pulse, we detect a significant decrease in cell proliferation from 2 to 22 months. Neuroblast numbers decrease with age, as do transitory amplifying progenitor cells, while both SVZ astrocytes and adjacent ependymal cells remain relatively constant. At 22 months, only residual pockets of neurogenesis remain and neuroblasts become restricted to the anterior dorsolateral horn of the SVZ. Within this dorsolateral zone many key components of the younger neurogenic niche are maintained; however, in the aged SVZ, increased numbers of SVZ astrocytes are found interposed within the ependyma. These astrocytes co-label with markers to ependymal cells and astrocytes, form intercellular adherens junctions with neighboring ependymal cells, and some possess multiple basal bodies of cilia within their cytoplasm. Together, these data reveal an age-related, progressive restriction of SVZ neurogenesis to the dorsolateral aspect of the lateral ventricle with increased numbers of SVZ astrocytes interpolated within the ependyma.}, Author = {Luo, Jie and Daniels, Stephen B. and Lennington, Jessica B. and Notti, Ryan Q. and Conover, Joanne C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1474-9718}, Journal = {Aging Cell}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {101130839}, Number = {2}, Organization = {Center for Regenerative Biology, Department of Physiology and Neurobiology, University of Connecticut, Storrs, 06250-4243, USA.}, Pages = {139-52}, Pii = {ACE197}, Pubmed = {16626393}, Title = {The aging neurogenic subventricular zone}, Uuid = {8CA566D5-0DDB-413F-B2AB-37CF86D4DC57}, Volume = {5}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1474-9726.2006.00197.x}} @article{Luo:2001, Author = {Luo, L. and Zong, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Mosaicism;23 Technique;Gene Expression Regulation, Developmental;Central Nervous System;Human;Genetic Markers;review, tutorial;Gene Targeting;Genes, Reporter;Neurons;review}, Medline = {21547537}, Month = {11}, Nlm_Id = {9809671}, Organization = {Department of Biological Sciences, Stanford University, Stanford, California 94305, USA. lluo\@stanford.edu}, Pages = {1158-9}, Pii = {nn1101-1158}, Pubmed = {11687823}, Title = {Single neuron labeling and genetic manipulation}, Uuid = {D2FD4A4C-658C-4703-B796-500A8B47E9E3}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Luo_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1101-1158}} @article{Luo:2001a, Abstract = {To define the relationship between glomerular activation patterns and neuronal olfactory responses in the main olfactory bulb, intracellular recordings were combined with optical imaging of intrinsic signals. Response correlation maps (RCMs) were constructed by correlating the fluctuations in membrane potential and firing rate during odorant presentations with patterns of glomerular activation. The RCMs indicated that mitral/tufted cells were excited by activation of a focal region surrounding their principal glomerulus and generally inhibited by activation of more distant regions. However, the structure of the RCMs and the relative contribution of excitatory and inhibitory glomerular input evolved and even changed sign during and after odorant application. These data suggest a dynamic center-surround organization of mitral/tufted cell receptive fields.}, Author = {Luo, M. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Neuron}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {6}, Organization = {Howard Hughes Medical Institute and Department of Neurobiology, Duke University Medical Center, 27710, Durham, NC, USA}, Pages = {1165-79.}, Title = {Response correlation maps of neurons in the Mammalian olfactory bulb}, Uuid = {2C846801-7538-41E3-ACCB-3A640BA84FBB}, Volume = {32}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11754845}} @article{Luo:2008, Abstract = {Understanding the principles of information processing in neural circuits requires systematic characterization of the participating cell types and their connections, and the ability to measure and perturb their activity. Genetic approaches promise to bring experimental access to complex neural systems, including genetic stalwarts such as the fly and mouse, but also to nongenetic systems such as primates. Together with anatomical and physiological methods, cell-type-specific expression of protein markers and sensors and transducers will be critical to construct circuit diagrams and to measure the activity of genetically defined neurons. Inactivation and activation of genetically defined cell types will establish causal relationships between activity in specific groups of neurons, circuit function, and animal behavior. Genetic analysis thus promises to reveal the logic of the neural circuits in complex brains that guide behaviors. Here we review progress in the genetic analysis of neural circuits and discuss directions for future research and development.}, Author = {Luo, Liqun and Callaway, Edward M. and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;Neural Pathways;Gene Expression Regulation;Nerve Net;Animals;Humans;Neurons;review;Technique;connectivity;connectome;genes;Gene Transfer Techniques;optogenetics;optical physiology;Viral Envelope Proteins;viral gene transfer}, Month = {3}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.}, Pages = {634-60}, Pii = {S0896-6273(08)00031-7}, Pubmed = {18341986}, Title = {Genetic dissection of neural circuits}, Uuid = {97D790D4-B66F-479A-9C8E-8D1F4C2EBD3B}, Volume = {57}, Year = {2008}, url = {papers/Luo_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.01.002}} @article{Luskin:1994, Abstract = {A spatially discrete region of the anterior part of the postnatal telencephalic subventricular zone, referred to as the SVZa generates vast numbers of lineally-related neurons destined for the olfactory bulb (Luskin, 1993). The cells originating in the SVZa migrate to the olfactory bulb along a highly restricted pathway which is in a direction orthogonal to the orientation of radial glial fibers. In this study we analysed the number, distribution, orientation and rate of migration of SVZa-derived cells as they approach the olfactory bulb. In order to track the SVZa-derived cells, a retroviral lineage tracer, encoding the reporter gene E. coli beta-galactosidase (lacZ) was injected precisely into the rat SVZa at postnatal day 1 (P1). The lacZ- positive cells were visualized 1, 2 and 3 days later by X-Gal histochemistry in cryostat sections. As the number of SVZa-derived cells in the pathway increased with survival time, their distribution changed systematically. The distribution pattern of lacZ-positive cells by 2 and 3 days postinjection suggested that some of the progeny of infected progenitor cells were undergoing neurogenesis as they proceeded to the olfactory bulb; a large percentage of the lacZ- positive cells were substantially displaced from the SVZa injection site. To investigate whether lacZ-positive cells migrate in a directed fashion, their orientation preference was scored. For the majority of lacZ-positive cells (>94\%), their leading process was directed toward the olfactory bulb, possibly reflecting a response to migratory cues present along the pathway. The estimated average rate of cell migration to the olfactory bulb was 23 mu m/h, which is approximately twice the speed of radially directed neuronal migration from the telencephalic ventricular zone to the cortical plate (O'Rourke et al., 1992). Collectively, these results suggest that SVZa-derived interneurons en route to the olfactory bulb may employ a novel mode of tangential migration.}, Author = {Luskin, M. B. and Boone, M. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Issn = {0379-864X}, Journal = {Chem Senses}, Keywords = {Genetic Vectors;Immunohistochemistry;Animals, Newborn/physiology;Telencephalon/*cytology/growth &development;Interneurons;Animals;beta-Galactosidase/biosynthesis/genetics;Escherichia coli/enzymology/genetics;Nerve Fibers;Research Support, U.S. Gov't, P.H.S.;Nerve Fibers/physiology;Olfactory Bulb/*cytology/growth &development;Olfactory Bulb;Support, U.S. Gov't, P.H.S.;Escherichia coli;Animal;B abstr;Rats, Sprague-Dawley;Retroviridae;beta-Galactosidase;02 Adult neurogenesis migration;Neuroglia/physiology;Rats;Neuroglia;Telencephalon;Retroviridae/genetics;Animals, Newborn;Support, Non-U.S. Gov't;Research Support, Non-U.S. Gov't;Interneurons/*physiology}, Medline = {95253832}, Month = {12}, Nlm_Id = {8217190}, Number = {6}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.}, Pages = {695-714.}, Pubmed = {7735848}, Title = {Rate and pattern of migration of lineally-related olfactory bulb interneurons generated postnatally in the subventricular zone of the rat}, Uuid = {A19AAF07-E157-4B67-85C7-6F5487670D12}, Volume = {19}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7735848}} @article{Luskin:2002, Abstract = {For the last 10 years our laboratory has been studying the proliferation, migration and differentiation of neuronal progenitor cells located in the anterior part of the postnatal forebrain subventricular zone (SVZa). SVZa-derived cells possess a number of proliferative characteristics that distinguish them from the other progenitor cells in the central nervous system. This review summarizes our recent findings, in which we compared the pattern of cell cycle inhibitory proteins expressed by the neonatal SVZa to that of telencephalic ventricular zone cells.}, Author = {Luskin, Marla B. and Coskun, Volkan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0379-864X}, Journal = {Chem Senses}, Keywords = {10 Development;Cell Differentiation;Cell Cycle Proteins;Animals;Protein p16;Humans;Cyclin-Dependent Kinase Inhibitor p19;Comparative Study;Cell Cycle;review;Cell Movement;Telencephalon;Prosencephalon;Cerebral Ventricles;03 Adult neurogenesis progenitor source;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Cyclin-Dependent Kinase Inhibitor p16;Neurons;Cell Division;Stem Cells}, Medline = {22137523}, Month = {7}, Nlm_Id = {8217190}, Number = {6}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA. luskin\@cellbio.emory.edu}, Pages = {577-80}, Pubmed = {12142335}, Title = {The progenitor cells of the embryonic telencephalon and the neonatal anterior subventricular zone differentially regulate their cell cycle}, Uuid = {47B68489-6B2C-4F38-8B40-FF97B3EBD943}, Volume = {27}, Year = {2002}} @article{Luskin:1994a, Abstract = {Although previous studies have revealed that the prenatal rat ventricular zone contains separate progenitor cells for neurons, astrocytes, and oligodendrocytes during the development of the cerebral cortex as early as the beginning of neurogenesis (Luskin et al., 1993; Grove et al., 1993), it is still unclear whether there are bipotential progenitor cells in the neonatal telencephalic subventricular zone which give rise to both astrocytes and oligodendrocytes during the peak of gliogenesis. To investigate this possibility, discrete groups of clonally related cells, generated by infecting progenitor cells of the neonatal subventricular zone with a retroviral lineage tracer, were analyzed ultrastructurally. An intracerebral injection of retrovirus encoding the reporter gene E. coli beta-galactosidase (lacZ) was made into the subventricular zone of newborn rats. Two weeks later their brains were perfused, sectioned, and histochemically reacted with X-Gal to identify at the light microscopic level clones of lacZ-positive cells. The sections were processed for electron microscopy to enable the identity of clonally related cells to be assessed at the ultrastructural level. All of the clones analyzed contained cells of the same phenotype and could be divided into four distinct types: immature cell clones situated in the subependymal zone surrounding the lateral ventricle, oligodendrocytes clones, and white or gray matter astrocyte clones. Not all of the cells in every clone displayed ultrastructural features of a mature cell. Rather, in some glial clones the lacZ-positive cells appeared to be at different stages of differentiation. However, we never encountered clones which contained both macroglial subtypes or clones containing neurons. Although the existence of bipotential progenitor cells cannot be completely dismissed, our results indicate the absence of progenitor cells in vivo in the neonatal subventricular zone which divide and generate astrocytes and oligodendrocytes. eng Journal Article}, Author = {Luskin, M. B. and McDermott, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Journal = {Glia}, Keywords = {Prosencephalon/*cytology/growth &development/ultrastructure;Rats;Stem Cells/physiology;Phenotype;beta-Galactosidase/metabolism;Animal;Rats, Sprague-Dawley;G abstr;11 Glia;Cerebral Ventricles/*cytology/growth &development/ultrastructure;Histocytochemistry;Gene Transfer Techniques;Animals, Newborn/*physiology;Support, Non-U.S. Gov't;Oligodendroglia/*physiology/ultrastructure;Astrocytes/*physiology/ultrastructure;Support, U.S. Gov't, P.H.S.;Microscopy, Electron;Clone Cells}, Number = {3}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.}, Pages = {211-26.}, Title = {Divergent lineages for oligodendrocytes and astrocytes originating in the neonatal forebrain subventricular zone}, Uuid = {C77FC097-C99F-4A3A-BAB2-28F3D2A08211}, Volume = {11}, Year = {1994}} @article{Luskin:1985, Abstract = {The 3H-thymidine method of birth-dating was used to determine when the cells belonging to each of the principal cellular layers of the cat's primary visual cortex are generated. In order to detect systematic differences in the position of radioactively labeled cells following 3H-thymidine administration at different prenatal ages, a geometric method was devised to represent the distribution of labeled cells in the form of depth histograms. Results show that visual cortical neurogenesis occurs largely during the second half of gestation between embryonic day 31 (E31) and E57. Cells of layer 6 are generated early, between E31 and E38, whereas cells destined for successively more superficial layers are generated at progressively later times. Layer 4 cells, the principal targets of geniculocortical afferents, are generated between E37 and E44. In addition, a special population of cells embedded in the white matter below layer 6 was found to be produced throughout the week-long period immediately prior to the onset of layer 6 neurogenesis. Overall, this radial pattern of cortical neurogenesis closely resembles the inside-first, outside-last, spatiotemporal sequence of development described for the monkey's primary visual cortex (Rakic, '74). In addition to finding this pronounced gradient in the radial dimension, we were also able to detect a less pronounced gradient along the tangential dimension: neurons destined for any given layer in the anterior part of the cortex (inferior visual field representation) are generated slightly in advance of neurons destined for more posterior regions (superior visual field). However even our more quantitative histogram analysis failed to reveal a mediolateral (central to peripheral visual field) gradient within area 17. In the cat, layers 6, 5, and 4 each take about a week to be generated, although their total cell numbers and packing densities differ in the adult. About 2 weeks are required to produce the cells of layers 2 and 3 combined. Furthermore, we found that neurons belonging to different layers and different morphological classes can be generated simultaneously. This suggests that the identity of a cortical neuron is not solely a function of the time of neurogenesis. 0021-9967 Journal Article}, Author = {Luskin, M. B. and Shatz, C. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Comp Neurol}, Keywords = {01 Adult neurogenesis general;Thymidine/diagnostic use;Cats;Female;Neurons/analysis/*physiology;Autoradiography;Visual Cortex/anatomy &histology/*growth &development;A,F abstr;Support, U.S. Gov't, P.H.S.;*Brain Mapping/methods;Animals;Age Factors;Male;Animals, Newborn/growth &development;Injections, Intravenous}, Number = {4}, Pages = {611-31}, Pubmed = {4086673}, Title = {Neurogenesis of the cat's primary visual cortex}, Uuid = {C3344955-15FE-4242-BF87-07AA5FF7E417}, Volume = {242}, Year = {1985}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4086673}} @article{Luskin:1998, Abstract = {The subventricular zone (SVZ) is the only germinal zone of the developing mammalian forebrain to persist postnatally. Although the SVZ has been known to give rise to most of the glial cells of the forebrain, several studies over the past few years have shown that the cells of the neonatal and adult SVZ can also generate neurons. Recent studies have demonstrated that a discrete region of the anterior part of the neonatal SVZ is composed exclusively of neuronal progenitor cells, whose progeny become interneurons of the olfactory bulb. This review will explore the properties that distinguish this anterior segment of the neonatal subventricular zone (SVZa) from the more posterior, gliogenic region. The cells of the SVZa, as well as its anterior extension forming the rostral migratory stream that enters the middle of the olfactory bulb, have antigenic characteristics of a neuronal phenotype, yet continue to divide during migration. In vitro, SVZa progenitor cells also retain a neuronal phenotype despite persistent division. Intriguingly, SVZa cells and their progeny migrate long distances along a highly stereotypical pathway. To better understand the guidance cues used by SVZa-derived cells during migration, both homotopic and heterotopic transplantation experiments have been conducted. SVZa cells homotopically transplanted into another animal's SVZa migrate with the recipient's endogenous SVZa cells in an indistinguishable manner, whereas those from the embryonic telencephalic ventricular zone, normally destined to follow radial glia to the cerebral cortex, fail to migrate following transplantation to the SVZa. SVZa cells transplanted heterotopically into the neonatal and adult striatum were able to disperse from their site of implantation. Thus, SVZa cells are special proliferating cells for which the rostral migratory stream is a particularly permissive pathway.}, Author = {Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {J Neurobiol}, Keywords = {Animals, Newborn/growth &development/*physiology;Olfactory Bulb/cytology/growth &development;02 Adult neurogenesis migration;B;Stem Cells/cytology/*physiology;Phenotype;Cell Line/physiology;Neurons/cytology/*physiology;Animal;Support, U.S. Gov't, P.H.S.;Prosencephalon/*cytology/growth &development;Support, Non-U.S. Gov't}, Number = {2}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.}, Pages = {221-33.}, Title = {Neuroblasts of the postnatal mammalian forebrain: their phenotype and fate}, Uuid = {46EA1F62-B88A-4E4F-8085-7CC8D2F8BCD0}, Volume = {36}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9712306}} @article{Luskin:1993, Abstract = {The diverse array of neurons and glia in the mammalian cerebral cortex arises from proliferating cells of the ventricular zone that surrounds the lateral ventricles of the developing brain. A fundamental but unresolved question is whether the individual cells of the ventricular zone are committed to producing progeny of only one particular phenotype or whether they generate progeny of more than one phenotype. We have begun to address this question by asking if individual cells of the ventricular zone generate exclusively neurons or glia at the onset of cortical neurogenesis in the rat. To assess the phenotypes of cells derived from a common progenitor cell, retroviral-mediated gene transfer was used to introduce the reporter gene, Escherichia coli beta-galactosidase, into ventricular zone cells at embryonic day 15 or 16. We used histochemistry to reveal beta-galactosidase-expressing cells in the mature rat cerebral cortex. Isolated clusters of beta-galactosidase-expressing cells, presumably clones, were identified in serial sections. Since the histochemical reaction product is electron dense, each cell could be examined at the ultrastructural level and assigned definitively to one of the major classes of cells in the cerebral cortex on the basis of well-established morphological criteria. This approach overcomes the problems of cell type identification encountered with light microscopy, where it is not always possible to distinguish between different cell phenotypes. We found that virtually all clones contained cells of exclusively one type: either all astrocytes, all oligodendrocytes, or all neurons. Furthermore, each particular cell type exhibited a different pattern and intensity of staining. The neuronal clones, with one exception, were composed of either all pyramidal cells (projection neurons), or all nonpyramidal cells (interneurons). The size and composition of neuronal clones did not seem related to their position in the cerebral cortex. Collectively, our observations indicate that separate progenitor cells exist for pyramidal neurons, nonpyramidal neurons, astrocytes, and oligodendrocytes. The striking phenotypic homogeneity in the clones arising from individual progenitor cells suggests that by the onset of cortical neurogenesis, at least some lineage restrictions have already occurred among the precursor cell population. Thus, our results suggest that lineage may play a pivotal role in determining some of the functionally important phenotypic attributes of cells in the cerebral cortex. eng Journal Article}, Author = {Luskin, M. B. and Parnavelas, J. G. and Barfield, J. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {10 Development;Cerebral Cortex/*cytology/enzymology/ultrastructure;Oligodendroglia/*cytology/enzymology/ultrastructure;beta-Galactosidase;Astrocytes;beta-Galactosidase/genetics/metabolism;Rats;Animals;Neuroglia/ultrastructure;Oligodendroglia;Animal;02 Adult neurogenesis migration;Neurons/*cytology/enzymology/ultrastructure;11 Glia;BB abstr;Cell Line;03 Adult neurogenesis progenitor source;Histocytochemistry;Support, Non-U.S. Gov't;Cerebral Cortex;Neuroglia;Neurons;Lac Operon;Support, U.S. Gov't, P.H.S.;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Stem Cells/*cytology/enzymology/ultrastructure;Astrocytes/*cytology/enzymology/ultrastructure;Research Support, Non-U.S. Gov't}, Medline = {93217553}, Month = {4}, Nlm_Id = {8102140}, Number = {4}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.}, Pages = {1730-50.}, Pubmed = {8463848}, Title = {Neurons, astrocytes, and oligodendrocytes of the rat cerebral cortex originate from separate progenitor cells: an ultrastructural analysis of clonally related cells}, Uuid = {69307C29-DC8E-4799-B9A6-346D5A18F77C}, Volume = {13}, Year = {1993}, url = {papers/Luskin_JNeurosci1993.pdf}} @article{Luskin:1997, Abstract = {A discrete area of the anterior part of the subventricular zone, or SVZa, of the postnatal forebrain is composed of progenitor cells that are dissimilar to those elsewhere in the CNS. In vivo SVZa progenitor cells retain the ability for division, even though they are phenotypically neurons. To characterize further the properties of SVZa cells, we have analyzed their characteristics in vitro using cell-type specific antibodies and their proliferative capacity by the incorporation of bromodeoxyuridine. At 2 h in vitro, as well as after 1 day in vitro, virtually all SVZa cells isolated from the neonatal forebrain express TuJ1, an antibody that recognizes neuron-specific tubulin, and are GFAP-negative. Likewise, the preponderance of SVZa cells express the neuron-specific markers N-CAM and MAP-2 when examined after 1 day in culture. The majority of SVZa cells cultured for as long as 8 days also possessed a neuronal phenotype. In addition, process- bearing TuJ1-positive SVZa cells continued to proliferate throughout the entire culture period. Thus, the neuronal progenitor cells of the SVZa constitute a unique cell population with characteristics distinct from the cells of other germinal zones. Using Smart Source Parsing}, Author = {Luskin, M. B. and Zigova, T. and Soteres, B. J. and Stewart, R. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {Prosencephalon/*cytology;Neurons/*cytology/*physiology;02 Adult neurogenesis migration;Animals, Newborn/*anatomy &histology;Support, Non-U.S. Gov't;03 Adult neurogenesis progenitor source;Rats;Stem Cells/*cytology/physiology;Phenotype;Cell Division;Animal;Support, U.S. Gov't, P.H.S.;Neurites/physiology;Cells, Cultured;Telencephalon/*cytology;BB abstr;Cerebral Ventricles}, Number = {5}, Organization = {Department of Anatomy, Emory University School of Medicine, George Washington University Medical Center, 2300 Eye St., N.W., Atlanta, Georgia, 30322, USA. luskin\@anatomy.emory.edu}, Pages = {351-66}, Title = {Neuronal progenitor cells derived from the anterior subventricular zone of the neonatal rat forebrain continue to proliferate in vitro and express a neuronal phenotype}, Uuid = {DE254ADF-4237-4775-88E4-5104143C9948}, Volume = {8}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9073397}} @article{Luskin:1988, Abstract = {To analyze cell lineage in the murine cerebral cortex, we infected progenitor cells with a recombinant retrovirus, then used the retroviral gene product to identify the descendants of infected cells. Cortices were infected on E12-E14 either in vivo or following dissociation and culture. In both cases, nearly all clones contained either neurons or glia, but not both. Thus, neuronal and glial lineages appear to diverge early in cortical development. To analyze the distribution of clonally related cells in vivo, clonal boundaries were reconstructed from serial sections. Perinatally (E18-PN0), clonally related cells were radially arrayed as they migrated to the cortical plate. Thus, clonal cohorts traverse a similar radial path. Following migration (PN7-PN23), neuronal clones generally remained radially arrayed, while glial clones were variable in orientation, suggesting that these two cell types accumulate in different ways. Neuronal clones sometimes spanned the full thickness of the cortex. Thus, a single progenitor can contribute neurons to several laminae.}, Author = {Luskin, M. B. and Pearlman, A. L. and Sanes, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cell Differentiation;10 Development;Neuroglia;Research Support, Non-U.S. Gov't;Retroviridae Proteins;Embryonic and Fetal Development;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Mice, Inbred C57BL;Retroviridae;15 Retrovirus mechanism;Mice;Animals;Cerebral Cortex;Neurons}, Medline = {90166544}, Month = {10}, Nlm_Id = {8809320}, Number = {8}, Organization = {Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110.}, Pages = {635-47}, Pubmed = {3272182}, Title = {Cell lineage in the cerebral cortex of the mouse studied in vivo and in vitro with a recombinant retrovirus}, Uuid = {AA6A06C6-2E8E-40FD-BFBA-31F2F47971AE}, Volume = {1}, Year = {1988}} @article{Luskin:1993a, Abstract = {The subventricular zone of the postnatal forebrain produces mainly glia, although it supports limited neurogenesis. To determine whether the subventricular zone is positionally specified, the phenotype and destination of the progeny of subventricular zone cells along the anterior-posterior axis of the lateral ventricles were analyzed. A retroviral lineage tracer containing the E. coli reporter gene lacZ was injected into different parts of the subventricular zone of neonatal rat pups, and at various times thereafter, the expression of beta- galactosidase was detected histochemically or immunohistochemically in the descendants of infected cells. A discrete region of the anterior part of the subventricular zone (SVZa) generated an immense number of neurons that differentiated into granule cells and periglomerular cells of the olfactory bulb-the two major types of interneurons. Thus, the SVZa appears to constitute a specialized source of neuronal progenitor cells. To reach the olfactory bulb, neurons arising in the SVZa migrate several millimeters along a highly restricted route. Guidance cues must be involved to prohibit widespread dispersion of these migrating neurons.}, Author = {Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Neuron}, Keywords = {Prosencephalon/*cytology;Cell Line/physiology;Cell Differentiation;Olfactory Bulb/cytology/physiology;Rats;Phenotype;Female;Animal;Rats, Sprague-Dawley;B-3;Cell Movement;Stem Cells/cytology;Neurons/*cytology/*physiology;Male;Time Factors;Animals, Newborn;Support, Non-U.S. Gov't;Lac Operon;Support, U.S. Gov't, P.H.S.;Cell Division}, Number = {1}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322.}, Pages = {173-89.}, Title = {Restricted proliferation and migration of postnatally generated neurons derived from the forebrain subventricular zone}, Uuid = {120ADD26-CD62-11D9-97C9-000D9346EC2A}, Volume = {11}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8338665}} @article{Luttenberg:1980, Author = {Luttenberg, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {0015-5640}, Journal = {Folia Morphol (Praha)}, Keywords = {Nerve Degeneration;Cats;Neural Pathways;Animals;24 Pubmed search results 2008;Frontal Lobe}, Medline = {81068181}, Nlm_Id = {0010076}, Number = {4}, Pages = {333-6}, Pubmed = {7439850}, Title = {Association systems of the cat's frontal cortex}, Uuid = {354A35EA-8D24-4A19-9665-C5AE50892647}, Volume = {28}, Year = {1980}} @article{Lubke:2007, Abstract = {A basic feature of the neocortex is its organization in functional, vertically oriented columns, recurring modules of signal processing and a system of transcolumnar long-range horizontal connections. These columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical columns contain thousands of neurons and span all cortical layers. They receive input from other cortical areas and subcortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a cortical column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of cortical signal processing and the underlying neuronal 'microcircuits'. In the last decade the 'barrel' field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a cortical column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a cortical column, with emphasis on excitatory signal flow.}, Author = {L{\"u}bke, Joachim and Feldmeyer, Dirk}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1863-2653}, Journal = {Brain Struct Funct}, Keywords = {Somatosensory Cortex;Synaptic Transmission;24 Pubmed search results 2008;Ventral Thalamic Nuclei;21 Neurophysiology;Pyramidal Cells;Neural Pathways;Receptors, Sensory;Afferent Pathways;Animals;Humans;Nerve Net;review;Neurons, Afferent}, Month = {7}, Nlm_Id = {101282001}, Number = {1}, Organization = {Research Centre J{\"u}lich, Institute of Neurosciences and Biophysics INB-3, Leo-Brandt-Str, 52425 J{\"u}lich, Germany.}, Pages = {3-17}, Pubmed = {17717695}, Title = {Excitatory signal flow and connectivity in a cortical column: focus on barrel cortex}, Uuid = {E6476333-66E4-453F-BBA1-9DE6207F450F}, Volume = {212}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00429-007-0144-2}} @article{Lubke:2000, Abstract = {Cortical columns are the functional units of the neocortex that are particularly prominent in the "barrel" field of the somatosensory cortex. Here we describe the morphology of two classes of synaptically coupled excitatory neurons in layer 4 of the barrel cortex, spiny stellate, and star pyramidal cells, respectively. Within a single barrel, their somata tend to be organized in clusters. The dendritic arbors are largely confined to layer 4, except for the distal part of the apical dendrite of star pyramidal neurons that extends into layer 2/3. In contrast, the axon of both types of neurons spans the cortex from layer 1 to layer 6. The most prominent axonal projections are those to layers 4 and 2/3 where they are largely restricted to a single cortical column. In layers 5 and 6, a small fraction of axon collaterals projects also across cortical columns. Consistent with the dense axonal projection to layers 4 and 2/3, the total number and density of boutons per unit axonal length was also highest there. Electron microscopy combined with GABA postimmunogold labeling revealed that most (>90\%) of the synaptic contacts were established on dendritic spines and shafts of excitatory neurons in layers 4 and 2/3. The largely columnar organization of dendrites and axons of both cell types, combined with the preferential and dense projections within cortical layers 4 and 2/3, suggests that spiny stellate and star pyramidal neurons of layer 4 serve to amplify thalamic input and relay excitation vertically within a single cortical column.}, Author = {L{\"u}bke, J. and Egger, V. and Sakmann, B. and Feldmeyer, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Synapses;10 Development;Dendrites;Rats;Pyramidal Cells;10 Spiny stellate;Electron Transport Complex IV;In Vitro;Rats, Wistar;10 Structural plasticity;Somatosensory Cortex;Animals;Support, Non-U.S. Gov't;Neurons;Axons}, Medline = {20341884}, Month = {7}, Nlm_Id = {8102140}, Number = {14}, Organization = {Anatomisches Institut I, Albert-Ludwigs-Universit{\"a}t Freiburg, D-79104 Freiburg, Germany. luebkejo\@uni-freiburg.de}, Pages = {5300-11}, Pii = {20/14/5300}, Pubmed = {10884314}, Title = {Columnar organization of dendrites and axons of single and synaptically coupled excitatory spiny neurons in layer 4 of the rat barrel cortex}, Uuid = {7BDFA014-911B-438C-A2BD-C7728C9D3A89}, Volume = {20}, Year = {2000}, url = {papers/Lübke_JNeurosci2000.pdf}} @article{Luthi:1994, Abstract = {A monoclonal antibody G39, generated against a protein extract of leech central nervous system, labels specific cell types in adult, embryonic, and regenerating preparations. The antibody stained glial cells, microglial cells, and connective tissue cells, but not neurons or muscle on cryosections. The staining pattern resembled that of an intracellular network. Affinity purification of the antigen revealed a 70 kD protein. Peptide sequencing showed significant homology of a stretch of 15 amino acids to squid neural filament protein. The same mAb G39 delineated glial cells as they formed during development of the CNS and showed that the giant neuropil glial cells appear before those in the packets. The antigen recognized by mAb G39 represents a nonneuronal intermediate filament of the leech Hirudo medicinalis found in various cell-types such as glia, microglia, and some cells of the connective tissue.}, Author = {L{\"u}thi, T. E. and Brodbeck, D. L. and Jen{\"o}, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Mice, Inbred BALB C;Electrophoresis, Polyacrylamide Gel;Animals;Sequence Homology, Amino Acid;Decapodiformes;Hydrogen-Ion Concentration;Leeches;Neurofilament Proteins;11 Glia;Concanavalin A;Antibodies, Monoclonal;Neuroglia;Blotting, Western;Mice;Nerve Crush;Central Nervous System;Molecular Sequence Data;Amino Acid Sequence;24 Pubmed search results 2008;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {94157531}, Month = {1}, Nlm_Id = {0213640}, Number = {1}, Organization = {Department of Pharmacology, Universit{\"a}t Basel, Switzerland.}, Pages = {70-82}, Pubmed = {8113784}, Title = {Identification of a 70 kD protein with sequence homology to squid neurofilament protein in glial cells of the leech CNS}, Uuid = {33F7CBE9-60F0-4EB4-B48E-5B78092EBC32}, Volume = {25}, Year = {1994}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.480250107}} @article{Lynch:1993, Abstract = {In this report, we have examined the role of central nervous system (CNS) development in the pathogenesis of neurodegenerative disease induced by murine retroviruses. This was accomplished by comparing the effect of delivering viruses, with either severe or marginal neurovirulence (J. L. Portis, S. Czub, C. F. Garon, and F. J. McAtee, J. Virol. 64:1648-1656, 1990), during the midgestational development of the mouse (gestation days 9 to 10). Midgestation inoculation of the marginally neurovirulent virus, 15-1, resulted in high level CNS infection, as determined by viral DNA and protein analysis. The high-level infection resulted in rapid, severe disease with 100\%incidence and an average clinical onset on postnatal day 17 (P17). The disease onset was comparable to that observed for the highly neurovirulent virus, FrCasE, when inoculated neonatally (onset ca. P16). To evaluate whether disease could be induced even earlier in CNS development, FrCasE was inoculated during midgestation. Surprisingly, neither clinical nor histological manifestations of CNS disease were accelerated but rather appeared at the same developmental time as seen for neonatally inoculated animals (onset of neuropathology at ca. P10; onset of clinical disease at ca. P15). CNS infection, on the other hand, occurred at earlier times (or = P10. This resulted in microglial engraftment and focal CNS infection unilaterally at the implantation sites and bilaterally along white matter tracts of the corpus callosum and pons and in cells of the subventricular layers of the lateral cerebral ventricles. Strikingly, focal spongiform degeneration colocalized with the sites of infection. In contrast to the wounding experiments, the implantation model was not associated with an inflammatory response or significant glial activation. Results of these studies suggest that (i) the developmental resistance of the CNS to infection lies at the blood-brain barrier and can be bypassed by direct introduction into the brain of virus-infected cells, (ii) the neuropathology induced by this virus is a consequence of local effects of the infection and does not appear to require endothelial or neuronal infection, and (iii) elements of the inflammatory response and/or glial activation may modulate the expression of neuropathology induced by neurovirulent retroviruses.}, Author = {Lynch, W. P. and Robertson, S. J. and Portis, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Animals;Nerve Degeneration;Blood-Brain Barrier;11 Glia;Microglia;Age Factors;Mice;Nervous System Diseases;Mice, Inbred Strains;Leukemia Virus, Murine}, Medline = {95156564}, Month = {3}, Nlm_Id = {0113724}, Number = {3}, Organization = {Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infections Diseases, Hamilton, Montana 59840.}, Pages = {1408-19}, Pubmed = {7853473}, Title = {Induction of focal spongiform neurodegeneration in developmentally resistant mice by implantation of murine retrovirus-infected microglia}, Uuid = {27C57D12-0F1B-4B8F-8FB2-AFEC1B0350A0}, Volume = {69}, Year = {1995}, url = {papers/Lynch_JVirol1995.pdf}} @article{Lynch:1996, Abstract = {CasBrE is a neurovirulent murine retrovirus which induces a spongiform myeloencephalopathy in susceptible mice. Genetic mapping studies have indicated that sequences responsible for neurovirulence reside within the env gene. To address the question of direct envelope protein neuroxicity in the central nervous system (CNS), we have generated chimeric mice expressing the CasBrE envelope protein in cells of neuroectodermal origin. Specifically, the multipotent neural progenitor cell line C17.2 was engineered to express the CasBrE env gene as either gp70/p15E (CasE) or gp70 alone (CasES). CasE expression in these cells resulted in complete (>10(5)) interference of superinfection with Friend murine leukemia virus clone FB29, whereas CasES expression resulted in a 1.8-log-unit decrease in FB29 titer. Introduction of these envelope-expressing C17.2 cells into the brains of highly susceptible IRW mice resulted in significant engraftment as integral cytoarchitecturally correct components of the CNS. Despite high-level envelope protein expression from the engrafted cells, no evidence of spongiform neurodegeneration was observed. To examine whether early virus replication events were necessary for pathogenesis, C17.2 cells expressing whole virus were transplanted into mice in which virus replication in the host was specifically restricted by Fv-1 to preintegration events. Again, significant C17.2 cell engraftment and infectious virus expression failed to precipitate spongiform lesions. In contrast, transplantation of virus-expressing C17.2 progenitor cells in the absence of the Fv-1 restriction resulted in extensive spongiform neurodegeneration by 2 weeks postengraftment. Cytological examination indicated that infection had spread beyond the engrafted cells, and in particular to host microglia. Spongiform neuropathology in these animals was directly correlated with CasBrE env expression in microglia rather than expression from neural progenitor cells. These results suggest that the envelope protein of CasBrE is not itself neurotoxic but that virus infectious events beyond binding and fusion in microglia are necessary for the induction of CNS disease.}, Author = {Lynch, W. P. and Snyder, E. Y. and Qualtiere, L. and Portis, J. L. and Sharpe, A. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Central Nervous System;Animals;Prion Diseases;Base Sequence;Brain;Microglia;Gene Products, gag;Retroviridae;11 Glia;Viral Envelope Proteins;Cell Line;Research Support, U.S. Gov't, P.H.S.;Mice;DNA, Viral;Virulence;Virus Replication;Retroviridae Proteins, Oncogenic;Gene Expression;Molecular Sequence Data;Research Support, Non-U.S. Gov't}, Medline = {97126095}, Month = {12}, Nlm_Id = {0113724}, Number = {12}, Organization = {Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. wonk\@mbcrr.harvard.edu}, Pages = {8896-907}, Pubmed = {8971019}, Title = {Late virus replication events in microglia are required for neurovirulent retrovirus-induced spongiform neurodegeneration: evidence from neural progenitor-derived chimeric mouse brains}, Uuid = {7B76721E-0ABC-42B8-A69A-D7E7A8AA0879}, Volume = {70}, Year = {1996}, url = {papers/Lynch_JVirol1996.pdf}} @article{Lynch:1999, Abstract = {The induction of spongiform myeloencephalopathy by murine leukemia viruses is mediated primarily by infection of central nervous system (CNS) microglia. In this regard, we have previously shown that CasBrE-induced disease requires late, rather than early, virus replication events in microglial cells (W. P. Lynch et al., J. Virol. 70:8896-8907, 1996). Furthermore, neurodegeneration requires the presence of unique sequences within the viral env gene. Thus, the neurodegeneration-inducing events could result from microglial expression of retroviral envelope protein alone or from the interaction of envelope protein with other viral structural proteins in the virus assembly and maturation process. To distinguish between these possible mechanisms of disease induction, we engineered the engraftable neural stem cell line C17-2 into packaging/producer cells in order to deliver the neurovirulent CasBrE env gene to endogenous CNS cells. This strategy resulted in significant CasBrE env expression within CNS microglia without the appearance of replication competent virus. CasBrE envelope expression within microglia was accompanied by increased expression of activation markers F4/80 and Mac-1 (CD11b) but failed to induce spongiform neurodegenerative changes. These results suggest that envelope expression alone within microglia is not sufficient to induce neurodegeneration. Rather, microglia-mediated disease appears to require neurovirulent Env protein interaction with other viral proteins during assembly or maturation. More broadly, the results presented here prove the efficacy of a novel method by which neural stem cell biology may be harnessed for genetically manipulating the CNS, not only for studying neurodegeneration but also as a paradigm for the disseminated distribution of retroviral vector-transduced genes.}, Author = {Lynch, W. P. and Sharpe, A. H. and Snyder, E. Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Gene Transfer Techniques;Research Support, Non-U.S. Gov't;Nerve Degeneration;Research Support, U.S. Gov't, P.H.S.;Not relevant;Stem Cells;Cell Line;11 Glia;Microglia;Support, U.S. Gov't, P.H.S.;Hematopoietic Stem Cell Transplantation;Retroviridae;Animals;Mice;Support, Non-U.S. Gov't;Retroviridae Infections;Genes, env}, Medline = {99329209}, Month = {8}, Nlm_Id = {0113724}, Number = {8}, Organization = {Department of Microbiology/Immunology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.}, Pages = {6841-51}, Pubmed = {10400782}, Title = {Neural stem cells as engraftable packaging lines can mediate gene delivery to microglia: evidence from studying retroviral env-related neurodegeneration}, Uuid = {ECC9382C-5756-43F1-BF6A-0AD45F36D4E5}, Volume = {73}, Year = {1999}, url = {papers/Lynch_JVirol1999.pdf}} @article{Lynch:2000, Abstract = {The wild mouse ecotropic retrovirus, Cas-Br-E, induces progressive, noninflammatory spongiform neurodegenerative disease in susceptible mice. Functional genetic analysis of the Cas-Br-E genome indicates that neurovirulence maps to the env gene, which encodes the surface glycoprotein responsible for binding and fusion of virus to host cells. To understand how the envelope protein might be involved in the induction of disease, we examined the regional and temporal expression of Cas-Br-E Env protein in the central nervous systems (CNS) of mice infected with the highly neurovirulent chimeric virus FrCas(E). We observed that multiple isoforms of Cas-Br-E Env were expressed in the CNS, with different brain regions exhibiting unique patterns of processed Env glycoprotein. Specifically, the expression of gp70 correlated with regions showing microglial infection and spongiform neurodegeneration. In contrast, regions high in neuronal infection and without neurodegenerative changes (the cerebellum and olfactory bulb) were characterized by a gp65 Env protein isoform. Sedimentation analysis of brain region extracts indicated that gp65 rather than gp70 was incorporated into virions. Biochemical analysis of the Cas-Br-E Env isoforms indicated that they result from differential processing of N-linked sugars. Taken together, these results indicate that differential posttranslational modification of the Cas-Br-E Env is associated with a failure to incorporate certain Env isoforms into virions in vivo, suggesting that defective viral assembly may be associated with the induction of spongiform neurodegeneration.}, Author = {Lynch, W. P. and Sharpe, A. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {review;Mice;Glycosylation;Not relevant;Gammaretrovirus;Protein Isoforms;11 Glia;Support, U.S. Gov't, P.H.S.;review, tutorial;Support, Non-U.S. Gov't;Animals;Retroviridae Infections;Viral Envelope Proteins;Brain}, Medline = {20094946}, Month = {2}, Nlm_Id = {0113724}, Number = {3}, Organization = {Department of Microbiology/Immunology, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA. wonk\@neoucom.edu}, Pages = {1558-65}, Pubmed = {10627570}, Title = {Differential glycosylation of the Cas-Br-E env protein is associated with retrovirus-induced spongiform neurodegeneration}, Uuid = {5DAC56DC-EA5F-46A3-B640-7B04E221DF50}, Volume = {74}, Year = {2000}, url = {papers/Lynch_JVirol2000.pdf}} @article{Lynch:1991, Abstract = {We have examined the pathological lesions and sites of infection in mice inoculated with a highly neurovirulent recombinant wild mouse ecotropic retrovirus (FrCasE). The spongiform lesions appeared initially as swollen postsynaptic neuronal processes, progressing to swelling in neuronal cell bodies, all in the absence of detectable gliosis. Infection of neurons in regions of vacuolation was not detected. However, high level infection of cerebellar granule neurons was observed in the absence of cytopathology, wherein viral protein was found associated with both axons and dendrites. Infection of ramified and amoeboid microglial cells was associated with cytopathology in the brain stem, and endothelial cell-pericyte infection was found throughout the CNS. No evidence of defective retroviral expression was observed. These results are consistent with an indirect mechanism of retrovirus-induced neuropathology.}, Author = {Lynch, W. P. and Czub, S. and McAtee, F. J. and Hayes, S. F. and Portis, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Nucleic Acid Hybridization;RNA Viruses;Cerebellar Cortex;Immunohistochemistry;Gene Products, env;Reassortant Viruses;Retroviridae;Not relevant;Virus Replication;11 Glia;Support, U.S. Gov't, P.H.S.;Blood Vessels;Animals;Mice;Retroviridae Infections;Neurons;Central Nervous System Diseases}, Medline = {92000683}, Month = {9}, Nlm_Id = {8809320}, Number = {3}, Organization = {Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Disease, National Institutes of Health, Hamilton, Montana 59840.}, Pages = {365-79}, Pubmed = {1654946}, Title = {Murine retrovirus-induced spongiform encephalopathy: productive infection of microglia and cerebellar neurons in accelerated CNS disease}, Uuid = {369DB0AE-B8DB-4F32-84CE-2CA6EF114609}, Volume = {7}, Year = {1991}, url = {papers/Lynch_Neuron1991.pdf}} @article{Lyons:2007, Abstract = {Deficits in cognitive function are associated with neuroinflammatory changes, typified by activation of glial cells and an alteration of the pro- and anti-inflammatory cytokine balance in the brain. Although there is evidence to suggest that activation of microglia is regulated by interaction with other cell types in the brain, the mechanism(s) involved is poorly understood. Here, we provide evidence that interaction between CD200 and its receptor plays a role in modulating microglial activation under conditions of chronic and acute inflammation of the brain. We report that interleukin-4 (IL-4) plays a central role in modulating expression of CD200 and identify a mechanism by which IL-4 directly controls microglial cell activation. Our findings provide the first demonstration of a role for IL-4 in modulating CD200 expression and suggest a mechanism for regulation of microglial activation in the intact CNS under inflammatory conditions.}, Author = {Lyons, Anthony and Downer, Eric J. and Crotty, Suzanne and Nolan, Yvonne M. and Mills, Kingston H. G. and Lynch, Marina A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Animals;Acute Disease;Rats;Interleukin-4;comparative study;Microglia;Antigens, CD;Mice, Inbred C57BL;Rats, Wistar;research support, non-u.s. gov't;11 Glia;Chronic Disease;Male;Membrane Glycoproteins;Mice;24 Pubmed search results 2008;Inflammation;Ligands}, Month = {8}, Nlm_Id = {8102140}, Number = {31}, Organization = {Trinity College Institute for Neuroscience, Physiology Department, Trinity College, Dublin 2, Ireland.}, Pages = {8309-13}, Pii = {27/31/8309}, Pubmed = {17670977}, Title = {CD200 ligand receptor interaction modulates microglial activation in vivo and in vitro: a role for IL-4}, Uuid = {BB7AC3FD-E4C9-44BA-8585-C9D764C9CA5A}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1781-07.2007}} @article{Ma:2003, Abstract = {BACKGROUND: Despite the meridian system being an important concept in Traditional Chinese Medicine (TCM), modern biology and Western medical systems have failed to find an anatomic substrate. Since the 1960s, a variety of phenomena along meridians have been reported, among which quite a few suggest that along meridians there is a fluid pathway (but not blood vessels or lymphatics). On the other hand, perivascular space (PVS) has been demonstrated to be a body fluid pathway in addition to blood vessels and lymphatics in some mammalian tissues, such as brain, thymus, and lung. OBJECTIVES: The present study was designed to examine the relationship between PVS and the meridian. We studied characteristics of the tissues around the blood vessels along the Stomach Meridian of Foot-Yangming and the Gallbladder Meridian of Foot-shaoyang, with the goal of identifying anatomical structure corresponding to the meridian described in TCM. DESIGN AND RESULTS: Through perivascular dye injection and frozen section histology, we found that there is PVS around the blood vessels along the meridians, and it is a fluid pathway. Subsequent physiologic studies revealed that the PVS shows significantly greater electrical conductivity and significantly higher partial oxygen pressure (pO(2)) compared to medial and lateral tissues. CONCLUSIONS: The PVS along the meridians has properties offering good explanation for the meridian phenomena. The work sheds new light on the studies of meridians and may contribute to research on the mechanism of Chinese acupuncture.}, Author = {Ma, Wentao and Tong, Hua and Xu, Weiya and Hu, Jiming and Liu, Nai and Li, Hongyi and Cao, Lianxin}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1075-5535}, Journal = {J Altern Complement Med}, Keywords = {Electric Conductivity;Research Support, Non-U.S. Gov't;Mice, Inbred BALB C;Female;Microscopy, Electron;Connective Tissue;Extracellular Fluid;Contrast Media;Meridians;Lymphatic Vessels;11 Glia;Rabbits;Male;Animals;Mice}, Month = {12}, Nlm_Id = {9508124}, Number = {6}, Organization = {Department of Analysis-Measurement Science, School of Life Sciences, Wuhan University, Wuhan 430-072, People's Republic of China.}, Pages = {851-9}, Pubmed = {14736357}, Title = {Perivascular space: possible anatomical substrate for the meridian}, Uuid = {A79F8A81-37D7-403C-95AD-C19BCD98ADAD}, Volume = {9}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/107555303771952208}} @article{Ma:2006, Abstract = {GABA-releasing inhibitory interneurons in the cerebral cortex can be classified by their neurochemical content, firing patterns, or axonal targets, to name the most common criteria, but whether classifications using different criteria converge on the same neuronal subtypes, and how many such subtypes exist, is a matter of much current interest and considerable debate. To address these issues, we generated transgenic mice expressing green fluorescent protein (GFP) under control of the GAD67 promoter. In two of these lines, named X94 and X98, GFP expression in the barrel cortex was restricted to subsets of somatostatin-containing (SOM+) GABAergic interneurons, similar to the previously reported "GIN" line (Oliva et al., 2000), but the laminar distributions of GFP-expressing (GFP+) cell bodies in the X94, X98, and GIN lines were distinct and nearly complementary. We compared neurochemical content and axonal distribution patterns of GFP+ neurons among the three lines and analyzed in detail electrophysiological properties in a dataset of 150 neurons recorded in whole-cell, current-clamp mode. By all criteria, there was nearly perfect segregation of X94 and X98 GFP+ neurons, whereas GIN GFP+ neurons exhibited intermediate properties. In the X98 line, GFP expression was found in infragranular, calbindin-containing, layer 1-targeting ("Martinotti") cells that had a propensity to fire low-threshold calcium spikes, whereas X94 GFP+ cells were stuttering interneurons with quasi fast-spiking properties, residing in and targeting the thalamo-recipient neocortical layers. We conclude that much of the variability previously attributed to neocortical SOM+ interneurons can be accounted for by their natural grouping into distinct subtypes.}, Author = {Ma, Yunyong and Hu, Hang and Berrebi, Albert S. and Mathers, Peter H. and Agmon, Ariel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Somatostatin;research support, n.i.h., extramural ;21 Neurophysiology;Neocortex;Neural Inhibition;Mice, Transgenic;Interneurons;12 Interneuron development;Animals;Cells, Cultured;Mice;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8102140}, Number = {19}, Organization = {Department of Neurobiology and Anatomy, West Virginia University, Morgantown, West Virginia 26506, USA.}, Pages = {5069-82}, Pii = {26/19/5069}, Pubmed = {16687498}, Title = {Distinct subtypes of somatostatin-containing neocortical interneurons revealed in transgenic mice}, Uuid = {83EF528C-27C2-4B0E-895F-4D377E8AE0E4}, Volume = {26}, Year = {2006}, url = {papers/Ma_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0661-06.2006}} @article{Ma:2006a, Abstract = {RNA interference (RNAi) in both plants and animals is mediated by small RNAs of approximately 21-23 nucleotides in length for regulation of target gene expression at multiple levels through partial sequence complementarities. Combined with widespread genome sequencing, experimental use of RNAi has the potential to interrogate systematically all genes in a given organism with respect to a particular function. However, owing to a tolerance for mismatches and gaps in base-pairing with targets, small RNAs could have up to hundreds of potential target sequences in a genome, and some small RNAs in mammalian systems have been shown to affect the levels of many messenger RNAs besides their intended targets. The use of long double-stranded RNAs (dsRNAs) in Drosophila, where Dicer-mediated processing produces small RNAs inside cells, has been thought to reduce the probability of such 'off-target effects' (OTEs). Here we show, however, that OTEs mediated by short homology stretches within long dsRNAs are prevalent in Drosophila. We have performed a genome-wide RNAi screen for novel components of Wingless (Wg) signal transduction in Drosophila S2R + cells, and found few, if any, legitimate candidates. Rather, many of the top candidates exert their effects on Wg response through OTEs on known pathway components or through promiscuous OTEs produced by tandem trinucleotide repeats present in many dsRNAs and genes. Genes containing such repeats are over-represented in candidate lists from published screens, suggesting that they represent a common class of false positives. Our results suggest simple measures to improve the reliability of genome-wide RNAi screens in Drosophila and other organisms.}, Author = {Ma, and Creanga, and Lum, and Beachy,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {23 RNAi;23 Technique}, Month = {9}, Nlm_Id = {0410462}, Organization = {Howard Hughes Medical Institute, Department of Molecular Biology and Genetics.}, Pii = {nature05179}, Pubmed = {16964239}, Title = {Prevalence of off-target effects in Drosophila RNA interference screens}, Uuid = {FEC9BD16-48A4-11DB-A317-000D9346EC2A}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05179}} @article{Ma:2002, Abstract = {The Sca-1 cell surface glycoprotein is used routinely as a marker of adult hematopoietic stem cells (HSCs), allowing a >100-fold enrichment of these rare cells from the bone marrow of the adult mouse. The Sca-1 protein is encoded by the Ly-6A/E gene, a small 4-exon gene that is tightly controlled in its expression in HSCs and several hematopoietic cell types. For the ability to sort and localize HSCs directly from the mouse, we initiated a transgenic approach in which we created Ly-6A (Sca-1) green fluorescent protein (GFP) transgenic mice. We show here that a 14-kb Ly-6A expression cassette directs the transcription of the GFP marker gene in all functional repopulating HSCs in the adult bone marrow. A >100-fold enrichment of HSCs occurred by sorting for the GFP-expressing cells. Furthermore, as shown by fluorescence-activated cell sorting and histologic analysis of several hematopoietic tissues, the GFP transgene expression pattern generally corresponded to that of Sca-1. Thus, the Ly-6A GFP transgene facilitates the enrichment of HSCs and presents the likelihood of identifying HSCs in situ.}, Author = {Ma, Xiaoqian and Robin, Catherine and Ottersbach, Katrin and Dzierzak, Elaine}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:35 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {Transgenes;Animals;Cell Separation;Bone Marrow Transplantation;Antigens, Ly;Indicators and Reagents;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Hematopoietic Stem Cell Transplantation;Mice, Inbred CBA;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;Age Factors;Mice;Hematopoietic Stem Cells;Luminescent Proteins;Membrane Proteins;Biological Markers;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {22345243}, Nlm_Id = {9304532}, Number = {6}, Organization = {Pathology Department, Erasmus University, Rotterdam, Netherlands.}, Pages = {514-21}, Pubmed = {12456959}, Title = {The Ly-6A (Sca-1) GFP transgene is expressed in all adult mouse hematopoietic stem cells}, Uuid = {89EFD174-8F46-4E21-BB9B-F7CBA6CC2115}, Volume = {20}, Year = {2002}} @article{MacFarlane:2000, Abstract = {Arrest of spinal cord astrocytes at defined stages of the cell cycle clock causes significant changes in the expression of voltage-activated Na(+) and K(+) currents. Arrest of actively proliferating astrocytes in G1/G0 by all-trans-retinoic acid induces premature expression of inwardly rectifying K(+) currents (IK(IR)) typically expressed only in differentiated astrocytes. By contrast, arrest in S phase by ara-C or Aphidicolin leads to a greater than twofold increase in "delayed"outwardly rectifying currents (IK(D)) and a concomitant decrease in IK(IR). Pharmacological blockade of IK(D) by TEA and 4AP caused proliferating astrocytes to arrest in G0/G1, suggesting that activity of these channels is required for G1/S checkpoint progression. Conversely, in quiescent astrocytes, inhibition of IK(IR) by 30 microM BaCl(2) led to an increase in astrocyte proliferation and to an increase in the number of cells in S phase from 5\%to 26\%. These data suggest that a downregulation of K(IR) promotes cell cycle progression through the G1/S checkpoint. Blockade of IK(IR) in actively proliferating cells, however, leads to an accumulation in G2/M, suggesting that reappearance of this current may be critical for progression beyond DNA synthesis. Interestingly, Na(+) currents (INa(+)) are increased greater than fourfold in S phase-arrested cells, yet their pharmacological blockade by TTX has no effect on cell cycle progression. However, the resting membrane potential of S phase-arrested cells increases profoundly, and manipulation of membrane potential by the application of low concentrations of ouabain, or reduction of extracellular potassium, induces the accumulation of quiescent astrocytes in S phase of the cell cycle, suggesting that either depolarization or intracellular sodium, or both, play an important role in promoting astrocyte proliferation. 0894-1491 Journal Article}, Author = {MacFarlane, S. N. and Sontheimer, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Glia}, Keywords = {Electrophysiology;Sodium Channels/metabolism/physiology;Membrane Potentials/physiology;Ion Channels/*metabolism;Rats;Sodium/metabolism;Animals;Cell Cycle/physiology;G, EE pdf;Rats, Sprague-Dawley;08 Aberrant cell cycle;Astrocytes/*cytology/*metabolism;Potassium Channels/physiology;Cell Division/physiology;Potassium Channel Blockers;Spinal Cord/*cytology/*metabolism;Support, U.S. Gov't, P.H.S.;S Phase/physiology;Intracellular Fluid/metabolism/physiology}, Number = {1}, Organization = {Department of Neurobiology, University of Alabama, Birmingham, Alabama, USA. macfarlan\@nrc.uab.edu}, Pages = {39-48}, Title = {Changes in ion channel expression accompany cell cycle progression of spinal cord astrocytes}, Uuid = {0D258350-606B-4DC2-9D9A-04AB3D843D7B}, Volume = {30}, Year = {2000}, url = {papers/MacFarlane_Glia2000.pdf}} @article{MacLean:2005, Abstract = {Although spontaneous activity occurs throughout the neocortex, its relation to the activity produced by external or sensory inputs remains unclear. To address this, we used calcium imaging of mouse thalamocortical slices to reconstruct, with single-cell resolution, the spatiotemporal dynamics of activity of layer 4 in the presence or absence of thalamic stimulation. We found spontaneous neuronal coactivations corresponded to intracellular UP states. Thalamic stimulation of sufficient frequency (>10 Hz) triggered cortical activity, and UP states, indistinguishable from those arising spontaneously. Moreover, neurons were activated in identical and precise spatiotemporal patterns in thalamically triggered and spontaneous events. The similarities between cortical activations indicate that intracortical connectivity plays the dominant role in the cortical response to thalamic inputs. Our data demonstrate that precise spatiotemporal activity patterns can be triggered by thalamic inputs and indicate that the thalamus serves to release intrinsic cortical dynamics.}, Author = {MacLean, Jason N. and Watson, Brendon O. and Aaron, Gloster B. and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Electric Stimulation;24 Pubmed search results 2008;research support, n.i.h., extramural ;21 Neurophysiology;research support, non-u.s. gov't ;in vitro ;Mice, Inbred C57BL;Neocortex;Animals, Newborn;Electrophysiology;Nerve Net;Animals;Mice;Reaction Time;Neurons;Thalamus}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10027, USA. JM2107\@columbia.edu}, Pages = {811-23}, Pii = {S0896-6273(05)01001-9}, Pubmed = {16337918}, Title = {Internal dynamics determine the cortical response to thalamic stimulation}, Uuid = {21409ED2-8EA4-4DD3-9BA3-DAF89C29C41F}, Volume = {48}, Year = {2005}, url = {papers/MacLean_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.09.035}} @article{Macas:2006, Abstract = {The adult human brain retains the capacity to generate new neurons in the hippocampal formation (Eriksson et al., 1998) and neuronal progenitor cells (NPCs) in the forebrain (Bernier et al., 2000), but to what extent it is capable of reacting to injuries, such as ischemia, is not known. We analyzed postmortem tissue from normal and pathological human brain tissue (n = 54) to study the cellular response to ischemic injury in the forebrain. We observed that cells expressing the NPC marker polysialylated neural adhesion cell molecule (PSA-NCAM) are continuously generated in the adult human subventricular zone (SVZ) and migrate along the olfactory tracts. These cells were not organized in migrating chains as in the adult rodent rostral migratory stream, and their number was lower in the olfactory tracts of brains from old (56-81 years of age) compared with young (29 + 36 years of age) individuals. Moreover, we show that in brains of patients of advanced age (60-87 years of age), ischemia led to an elevated number of Ki-67-positive cells in the ipsilateral SVZ without concomitant apoptotic cell death. Additionally, ischemia led to an increased number of PSA-NCAM-positive NPCs close to the lateral ventricular walls, compared with brains of comparable age without obvious neuropathologic changes. These results suggest that the adult human brain retains a capacity to respond to ischemic injuries and that this capacity is maintained even in old age.}, Author = {Macas, Jadranka and Nern, Christian and Plate, Karl H. and Momma, Stefan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Aging;Cell Differentiation;research support, non-u.s. gov't;Adult;Aged;Aged, 80 and over;Cell Proliferation;Stem Cells;Middle Aged;Lateral Ventricles;comparative study;Prosencephalon;Humans;Cell Movement;24 Pubmed search results 2008;Neurons}, Month = {12}, Nlm_Id = {8102140}, Number = {50}, Organization = {Institute of Neurology (Edinger Institute), University of Frankfurt, D-60528 Frankfurt, Germany.}, Pages = {13114-9}, Pii = {26/50/13114}, Pubmed = {17167100}, Title = {Increased generation of neuronal progenitors after ischemic injury in the aged adult human forebrain}, Uuid = {4A808686-54FC-4917-978E-68460A4BC331}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4667-06.2006}} @article{Macdonald:2006, Abstract = {Neuron-glia communication is central to all nervous system responses to trauma, yet neural injury signaling pathways remain poorly understood. Here we explore cellular and molecular aspects of neural injury signaling in Drosophila. We show that transected Drosophila axons undergo injury-induced degeneration that is morphologically similar to Wallerian degeneration in mammals and can be suppressed by the neuroprotective mouse Wld(s) protein. Axonal injury elicits potent morphological and molecular responses from Drosophila glia: glia upregulate expression of the engulfment receptor Draper, undergo dramatic changes in morphology, and rapidly recruit cellular processes toward severed axons. In draper mutants, glia fail to respond morphologically to axon injury, and severed axons are not cleared from the CNS. Thus Draper appears to act as a glial receptor for severed axon-derived molecular cues that drive recruitment of glial processes to injured axons for engulfment.}, Author = {Macdonald, Jennifer M. and Beach, Margaret G. and Porpiglia, Ermelinda and Sheehan, Amy E. and Watts, Ryan J. and Freeman, Marc R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Neuroglia;Wallerian Degeneration;Membrane Proteins;research support, non-u.s. gov't ;Animals, Genetically Modified;Drosophila Proteins;Nerve Tissue Proteins;Drosophila;10 Structural plasticity;Animals;comparative study ;24 Pubmed search results 2008;Axons}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.}, Pages = {869-81}, Pii = {S0896-6273(06)00319-9}, Pubmed = {16772169}, Title = {The Drosophila cell corpse engulfment receptor draper mediates glial clearance of severed axons}, Uuid = {D7312C6C-E02E-40AF-9EEE-E44E934C0848}, Volume = {50}, Year = {2006}, url = {papers/Macdonald_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.04.028}} @article{Macklis:1993, Abstract = {Selective degeneration of neocortical callosal pyramidal neurons by noninvasive laser illumination was used for directed studies of neocortical transplantation, to test the hypothesis that transplanted embryonic neurons may seek to restore normal cytoarchitecture within an appropriately permissive local environment. At long wavelengths that penetrate through tissue without major absorption, photolysis can cause extremely selective degeneration to desired subpopulations of targeted neurons in vivo (Macklis and Madison, 1991; Madison and Macklis, 1993). Cell death is geographically defined and slowly progressive, allowing control over the anatomical substrate for transplantation. Targeting occurs by retrograde incorporation of cytolytic chromophores that are activated by specific-wavelength light. Intermixed neurons, glia, axons, blood vessels, and connective tissue remain intact. Degeneration was effected within neocortical lamina II/III of neonatal mouse pups following targeting in utero or early postnatally with photoactive nanospheres. Total neuron density was reduced typically by 25-30\%within defined areas, with approximately 60\%loss of large projection neurons and no change in the number of small, presumptive interneurons. Embryonic day 17 neocortical cell suspensions, which included recently postmitotic neurons destined to form lamina II/III, were transplanted lateral to these regions of ongoing neuron degeneration in juvenile mice. Cellular injections spanned laminae II-V, to provide donor neurons with both lateral and laminar choice for possible migration and integration. Donor cells were labeled in vitro with unique fluorescent and electron-dense nanospheres that allowed distinct identification of donor cells at both light and electron microscopic levels. Control experiments included neocortical transplants into intact age-matched hosts, into hosts with kainic acid lesions to neocortex, or distant to the region of photolytic neuronal degeneration; embryonic cerebellar transplants to the regions of selective photolytic degeneration; and grafts of hypoosmotically lysed neocortical cells to lesioned regions. After survival times of 1 hr to 12 weeks, labeled neurons were identified morphologically and positions were digitized for qualitative and quantitative analysis of position and specificity of migration and cellular integration; electron microscopy was used to confirm further the donor identities of migrated neurons. Neurons placed near host zones of photolytic neuron degeneration migrated up to 780 microns specifically within these zones; approximately 44\%of donor neurons migrated significantly beyond the injection site to enter these regions. Migration and integration did not occur in normal, unaffected deeper layers IV-VI of these experimental mice, or in the normal lamina II/III bordering the transplantation site on the side opposite the neuron-deficient region. Control grafts of all five types revealed only minimal local spread without laminar preference.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Lasers;Nerve Degeneration;Animals;Cells, Cultured;Brain Tissue Transplantation;Photolysis;Cell Movement;Mice, Inbred C57BL;Fetal Tissue Transplantation;17 Transplant Regeneration;Embryo;Pyramidal Tracts;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neurons;06 Adult neurogenesis injury induced;Mice;Microscopy, Electron;Corpus Callosum;Research Support, Non-U.S. Gov't}, Medline = {93375318}, Month = {9}, Nlm_Id = {8102140}, Number = {9}, Organization = {Department of Neurology, Harvard Medical School, Boston, Massachusetts.}, Pages = {3848-63}, Pubmed = {8366349}, Title = {Transplanted neocortical neurons migrate selectively into regions of neuronal degeneration produced by chromophore-targeted laser photolysis}, Uuid = {C9CC07D7-DF55-4496-98D1-C2FE9C457049}, Volume = {13}, Year = {1993}, url = {papers/Macklis_JNeurosci1993.pdf}} @article{Mackowiak:2007, Abstract = {Recent evidence indicates that the polysialylated neural cell adhesion molecule (PSA-NCAM) is involved in hippocampal plasticity. On the other hand, CB1 receptor activation is known to disturb some hippocampal processes involving plastic changes, such as learning and memory. Therefore, the present study investigated the effect of HU-210, a CB1 receptor agonist, on the expression of PSA-NCAM protein in the dentate gyrus (DG) and CA3 region of the rat hippocampus. It was found that at a dose of 0.1 mg/kg i.p. of HU-210, the number of PSA-NCAM immunoreactive (IR) cells in the DG declined in a time-dependent manner. The decrease in PSA-NCAM expression was observed at 1 and 2 days (ca. 21\%and 30\%, respectively), but not after 4 h and 4 days following HU-210 administration. However, HU-210 treatment did not change the length density of PSA-NCAM immunopositive processes in CA3 mossy fibers at all the time points measured. The effect observed in the DG on day 2 was blocked by AM-251 (1 mg/kg, i.p.), a CB1 receptor antagonist, given 30 min before HU-210. Neither the number of Ki-67 (IR) cells (a marker of proliferation) nor the number of doublecortin-IR cells (a marker of immature neurons) was affected by HU-210 (0.1 mg/kg, i.p.) treatment at any of the time points. An analysis of co-localization of CB1 receptor protein with PSA-NCAM protein revealed that both proteins were not present in the same population of neurons in the subgranular layer of the DG. The observed changes in PSA-NCAM expression were not related to the reduction of proliferation or differentiation of newly born cells, but were possible due to alternations in the synaptic activity in the DG. However, such alteration in the PSA-NCAM expression may change the timing of the functional maturation of newly born neurons. Moreover, the above finding suggests that acute activation of CB1 receptors may result in the stiffening of the hippocampal structure and susceptibility to plastic changes and may lead to functional impairment governed by alterations in the hippocampal structure.}, Author = {Ma\'{c}kowiak, and Chocyk, and Markowicz-Kula, and Wdzony,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {02 Adult neurogenesis migration;04 Adult neurogenesis factors;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0045503}, Organization = {Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krak{\'o}w, 12 Smtna Street, Poland.}, Pii = {S0006-8993(07)00343-5}, Pubmed = {17355876}, Title = {Acute activation of CB1 cannabinoid receptors transiently decreases PSA-NCAM expression in the dentate gyrus of the rat hippocampus}, Uuid = {F3DDE5C9-A991-45E3-AF7B-67E3FE47B800}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainres.2007.02.014}} @article{Madaule:1998, Abstract = {During mitosis, a ring containing actin and myosin appears beneath the equatorial surface of animal cells. This ring then contracts, forms a cleavage furrow and divides the cell, a step known as cytokinesis. The two daughter cells often remain connected by an intercellular bridge which contains a refringent structure known as the midbody. How the appearance of this ring is regulated is unclear, although the small GTPase Rho, which controls the formation of actin structures, is known to be essential. Protein kinases are also thought to participate in cytokinesis. We now show that a splice variant of a Rho target protein, named citron, contains a protein kinase domain that is related to the Rho-associated kinases ROCK14 and ROK, which regulate myosin-based contractility. Citron kinase localizes to the cleavage furrow and midbody of HeLa cells; Rho is also localized in the midbody. We find that overexpression of citron mutants results in the production of multinucleate cells and that a kinase-active mutant causes abnormal contraction during cytokinesis. We propose that citron kinase regulates cytokinesis at a step after Rho in the contractile process. 98361238 0028-0836 Journal Article}, Author = {Madaule, P. and Eda, M. and Watanabe, N. and Fujisawa, K. and Matsuoka, T. and Bito, H. and Ishizaki, T. and Narumiya, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Nature}, Keywords = {GTP-Binding Proteins/*physiology;GTP Phosphohydrolases/*physiology;Transfection;Sequence Homology, Amino Acid;Molecular Sequence Data;Hela Cells;Human;Proteins/chemistry/genetics/*physiology;Alternative Splicing;CK;Amino Acid Sequence;Protein-Serine-Threonine Kinases/chemistry/metabolism;Cell Division/*physiology;Support, Non-U.S. Gov't;rho GTP-Binding Proteins}, Number = {6692}, Organization = {Department of Pharmacology, Kyoto University Faculty of Medicine, Japan.}, Pages = {491-4}, Title = {Role of citron kinase as a target of the small GTPase Rho in cytokinesis}, Uuid = {AD8AF47C-A3E5-11DA-AB00-000D9346EC2A}, Volume = {394}, Year = {1998}, url = {papers/Madaule_Nature1998}} @article{Madsen:2000, Abstract = {BACKGROUND: Electroconvulsive therapy (ECT) is a widely used and efficient treatment modality in psychiatry, although the basis for its therapeutic effect is still unknown. Past research has shown seizure activity to be a regulator of neurogenesis in the adult brain. This study examines the effect of a single and multiple electroconvulsive seizures on neurogenesis in the rat dentate gyrus. METHODS: Rats were given either a single or a series of 10 electroconvulsive seizures. At different times after the seizures, a marker of proliferating cells, Bromodeoxyuridine (BrdU), was administered to the animals. Subsequently, newborn cells positive for BrdU were counted in the dentate gyrus. Double staining with a neuron-specific marker indicated that the newborn cells displayed a neuronal phenotype. RESULTS: A single electroconvulsive seizure significantly increased the number of new born cells in the dentate gyrus. These cells survived for at least 3 months. A series of seizures further increased neurogenesis, indicating a dose-dependent mechanism. CONCLUSIONS: We propose that generation of new neurons in the hippocampus may be an important neurobiologic element underlying the clinical effects of electroconvulsive seizures.}, Author = {Madsen, T. M. and Treschow, A. and Bengzon, J. and Bolwig, T. G. and Lindvall, O. and Tingstr{\"o}m, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0006-3223}, Journal = {Biol Psychiatry}, Keywords = {Animals;Rats;Microscopy, Confocal;Phenotype;Apoptosis;Electroconvulsive Therapy;Cell Count;Rats, Wistar;Antimetabolites;Male;Neurons;Dentate Gyrus;Fluorescent Antibody Technique, Direct;Cell Division;Immunohistochemistry;Bromodeoxyuridine;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {20322947}, Month = {6}, Nlm_Id = {0213264}, Number = {12}, Organization = {Neuropsychiatry Laboratory, Department of Psychiatry, H:S Rigshospitalet, (TMM, TGB), Copenhagen, Denmark.}, Pages = {1043-9}, Pii = {S0006322300002286}, Pubmed = {10862803}, Title = {Increased neurogenesis in a model of electroconvulsive therapy}, Uuid = {99B37E3F-3704-4A0B-A6CC-F4CE3E6A1D25}, Volume = {47}, Year = {2000}} @article{Madsen:2003, Abstract = {The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21 days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired in a hippocampus-independent object-recognition task. These results are in line with other reports documenting the functional significance of newly generated neurons in this region. As our irradiation procedure models prophylactic cranial irradiation used in the treatment of different cancers, we suggest that blocked neurogenesis contributes to the reported deleterious side effects of this treatment, consisting of memory impairment, dysphoria and lethargy. 0306-4522 Journal Article}, Author = {Madsen, T. M. and Kristjansen, P. E. and Bolwig, T. G. and Wortwein, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Neuroscience}, Keywords = {Cell Division/physiology/*radiation effects;Maze Learning/physiology/radiation effects;Exploratory Behavior/physiology/radiation effects;Dentate Gyrus/growth &development/*physiopathology/*radiation effects;Neurons/physiology/*radiation effects;Memory Disorders/*etiology/pathology/physiopathology;Rats;Immunohistochemistry;Rats, Wistar;06 Adult neurogenesis injury induced;Radiotherapy/*adverse effects;D pdf;Animals;Support, Non-U.S. Gov't;Bromodeoxyuridine/diagnostic use;Male;Stem Cells/physiology/*radiation effects}, Number = {3}, Organization = {Laboratory of Neuropsychiatry, Department of Psychiatry O-6102, H:S Rigshospitalet, Blegdamsvej 9, 2100, Copenhagen, Denmark.}, Pages = {635-42}, Pubmed = {12809684}, Title = {Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat}, Uuid = {B5B155C1-A944-4583-825E-CA871C4C660C}, Volume = {119}, Year = {2003}, url = {papers/Madsen_Neuroscience2003}} @article{Maffei:2004, Abstract = {Visual deprivation during a developmental sensitive period markedly alters visual cortical response properties, but the changes in intracortical circuitry that underlie these effects are poorly understood. Here we use a slice preparation of rat primary visual cortex to show that 2 d of prior visual deprivation early in life increases the excitability of layer 4 circuitry. Slice recordings showed that spontaneous activity of layer 4 star pyramidal neurons increased 25-fold after 2 d of visual deprivation between postnatal days (P) 15 and P17. This effect was mediated by increased net excitatory and decreased net inhibitory synaptic drive. Paired recordings showed that excitatory connections between star pyramidal neurons doubled in amplitude, whereas inhibitory connections decreased or increased depending on the interneuron class. These effects reversed when vision was restored. This dynamic adjustment of the excitation-inhibition balance may allow the networks within layer 4 to maintain stable levels of activity in the face of variable sensory input.}, Author = {Maffei, Arianna and Nelson, Sacha B. and Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Visual Cortex;Sensory Deprivation;research support, u.s. gov't, p.h.s. ;24 Pubmed search results 2008;21 Neurophysiology;Rats;Neuronal Plasticity;Animals, Newborn;Synaptic Transmission;Nerve Net;Animals;comparative study ;comparative study;Vision, Monocular;research support, u.s. gov't, p.h.s.}, Month = {12}, Nlm_Id = {9809671}, Number = {12}, Organization = {Department of Biology and Volen National Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454, USA.}, Pages = {1353-9}, Pii = {nn1351}, Pubmed = {15543139}, Title = {Selective reconfiguration of layer 4 visual cortical circuitry by visual deprivation}, Uuid = {185FC868-43C7-4D1A-9C50-67151F68192E}, Volume = {7}, Year = {2004}, url = {papers/Maffei_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1351}} @article{Maffei:2006, Abstract = {The fine-tuning of circuits in sensory cortex requires sensory experience during an early critical period. Visual deprivation during the critical period has catastrophic effects on visual function, including loss of visual responsiveness to the deprived eye, reduced visual acuity, and loss of tuning to many stimulus characteristics. These changes occur faster than the remodelling of thalamocortical axons, but the intracortical plasticity mechanisms that underlie them are incompletely understood. Long-term depression of excitatory intracortical synapses has been proposed as a general candidate mechanism for the loss of cortical responsiveness after visual deprivation. Alternatively (or in addition), the decreased ability of the deprived eye to activate cortical neurons could be due to enhanced intracortical inhibition. Here we show that visual deprivation leaves excitatory connections in layer 4 (the primary input layer to cortex) unaffected, but markedly potentiates inhibitory feedback between fast-spiking basket cells (FS cells) and star pyramidal neurons (star pyramids). Further, a previously undescribed form of long-term potentiation of inhibition (LTPi) could be induced at synapses from FS cells to star pyramids, and was occluded by previous visual deprivation. These data suggest that potentiation of inhibition is a major cellular mechanism underlying the deprivation-induced degradation of visual function, and that this form of LTPi is important in fine-tuning cortical circuitry in response to visual experience.}, Author = {Maffei, Arianna and Nataraj, Kiran and Nelson, Sacha B. and Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Long-Term Potentiation;research support, n.i.h., extramural ;Feedback, Biochemical;Photic Stimulation;Synapses;Animals;Rats;Visual Perception;Patch-Clamp Techniques;Vision, Monocular;in vitro ;Long-Term Depression (Physiology);Pyramidal Cells;21 Neurophysiology;21 Activity-development;24 Pubmed search results 2008;Visual Cortex;Excitatory Postsynaptic Potentials}, Month = {9}, Nlm_Id = {0410462}, Number = {7107}, Organization = {Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454, USA.}, Pages = {81-4}, Pii = {nature05079}, Pubmed = {16929304}, Title = {Potentiation of cortical inhibition by visual deprivation}, Uuid = {EAD34B1C-9957-4561-8748-43769CAAA9C3}, Volume = {443}, Year = {2006}, url = {papers/Maffei_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05079}} @article{Magavi:2000, Abstract = {Neurogenesis normally only occurs in limited areas of the adult mammalian brain--the hippocampus, olfactory bulb and epithelium, and at low levels in some regions of macaque cortex. Here we show that endogenous neural precursors can be induced in situ to differentiate into mature neurons, in regions of adult mammalian neocortex that do not normally undergo any neurogenesis. This differentiation occurs in a layer- and region-specific manner, and the neurons can re-form appropriate corticothalamic connections. We induced synchronous apoptotic degeneration of corticothalamic neurons in layer VI of anterior cortex of adult mice and examined the fates of dividing cells within cortex, using markers for DNA replication (5-bromodeoxyuridine; BrdU) and progressive neuronal differentiation. Newly made, BrdU- positive cells expressed NeuN, a mature neuronal marker, in regions of cortex undergoing targeted neuronal death and survived for at least 28 weeks. Subsets of BrdU+ precursors expressed Doublecortin, a protein found exclusively in migrating neurons, and Hu, an early neuronal marker. Retrograde labelling from thalamus demonstrated that BrdU+ neurons can form long-distance corticothalamic connections. Our results indicate that neuronal replacement therapies for neurodegenerative disease and CNS injury may be possible through manipulation of endogenous neural precursors in situ.}, Author = {Magavi, S. S. and Leavitt, B. R. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Transcription Factors;Nerve Degeneration;Cell Differentiation;Animals;Neocortex/cytology/*physiology;Aging;Transcription Factors/immunology/metabolism;Neurons/*cytology;Antigens, Differentiation/metabolism;Antigens, Differentiation;Neocortex;Aging/physiology;D-12;Animal;Cell Movement;Apoptosis;Nerve Regeneration;Bromodeoxyuridine/metabolism;Support, Non-U.S. Gov't;Research Support, U.S. Gov't, P.H.S.;Neurons;Support, U.S. Gov't, P.H.S.;Mice;Bromodeoxyuridine;Research Support, Non-U.S. Gov't}, Medline = {20335883}, Month = {6}, Nlm_Id = {0410462}, Number = {6789}, Organization = {Division of Neuroscience, Children's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {951-5.}, Pubmed = {10879536}, Title = {Induction of neurogenesis in the neocortex of adult mice}, Uuid = {BAA16A96-C26D-11DA-969D-000D9346EC2A}, Volume = {405}, Year = {2000}, url = {papers/Magavi_Nature2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35016083}} @article{Magavi:2001, Abstract = {Over the past three decades, research exploring potential neuronal replacement therapies have focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. Over most of the past century of modern neuroscience, it was thought that the adult brain was completely incapable of generating new neurons. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain, and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent findings from our lab demonstrate that it is possible to induce neurogenesis de novo in the adult mammalian brain, particularly in the neocortex where it does not normally occur, and that it may become possible to manipulate endogenous multipotent precursors in situ to replace lost or damaged neurons. Elucidation of the relevant molecular controls may allow the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that do not require transplantation of exogenous cells.}, Author = {Magavi, S. S. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Neuropsychopharmacology}, Keywords = {Stem Cells/*physiology;Neurons/*physiology;Epithelium/physiology;Olfactory Bulb/physiology;Human;D;06 Adult neurogenesis injury induced;Animal;Hippocampus/cytology/growth &development/physiology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Mice;Vertebrates/physiology;Neocortex/cytology/*growth &development/physiology}, Number = {6}, Organization = {Division of Neuroscience, Children's Hospital, Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {816-35.}, Title = {Manipulation of neural precursors in situ: induction of neurogenesis in the neocortex of adult mice}, Uuid = {A0E7C1DA-618A-4314-AAF8-02DBBE3BFE80}, Volume = {25}, Year = {2001}, url = {papers/Magavi_Neuropsychopharmacology2001.pdf}} @article{Mager:1985, Abstract = {The properties of clonogenic and leukemic cells, derived from mice infected with different helper virus pseudotypes of the polycythemic strain of Friend spleen focus-forming virus (SFFVp), have been analyzed. Four different replication-competent murine leukemia viruses (MuLVs) were used as helpers for the defective SFFVp genome: the Friend MuLVs, Moloney MuLV, and an amphotropic MuLV. Three different biological parameters were measured: (i) the kinetics of emergence of clonogenic cells characteristic of the late stages of Friend erythroleukemia; (ii) the ability of cells in these colonies to give rise to secondary colonies (self-renewal capacity); and (iii) the capacity of cell lines derived from these colonies to respond to inducers of erythroid differentiation. The properties of these cells was found to be independent of the helper virus used, suggesting that it is the SFFVp genome, not the helper virus, that plays a determinant role in the late stages of erythroleukemia. 0042-6822 Journal Article}, Author = {Mager, D. L. and Bernstein, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:56 -0400}, Journal = {Virology}, Keywords = {Friend murine leukemia virus/physiology;Cell Differentiation;Animals;Helper Viruses/*physiology;Erythropoiesis;Erythropoietin/pharmacology;Leukemia Virus, Murine/*genetics/*physiology;EE, DMSO, abstr;08 Aberrant cell cycle;Dimethyl Sulfoxide/pharmacology;Cell Line;Genes, Viral;Support, Non-U.S. Gov't;Moloney murine leukemia virus/physiology;Hematopoietic Stem Cells/*pathology;Hemoglobins/biosynthesis;Spleen/pathology;Cell Division;Mice;Spleen Focus-Forming Viruses/*genetics/physiology;Clone Cells;Leukemia, Erythroblastic, Acute/*microbiology/pathology}, Number = {2}, Pages = {337-41}, Pubmed = {3002024}, Title = {Induction of clonogenic and erythroleukemic cells by different helper virus pseudotypes of Friend spleen focus-forming virus}, Uuid = {0148F92C-A095-4FAC-84B3-2A3AB5861B92}, Volume = {141}, Year = {1985}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3002024}} @article{Mainen:1999, Abstract = {Two-photon excitation laser scanning microscopy (TPLSM) has become the tool of choice for high-resolution fluorescence imaging in intact neural tissues. Compared with other optical techniques, TPLSM allows high-resolution imaging and efficient detection of fluorescence signal with minimal photobleaching and phototoxicity. The advantages of TPLSM are especially pronounced in highly scattering environments such as the brain slice. Here we describe our approaches to imaging various aspects of synaptic function in living brain slices. To combine several imaging modes together with patch-clamp electrophysiological recordings we found it advantageous to custom-build an upright microscope. Our design goals were primarily experimental convenience and efficient collection of fluorescence. We describe our TPLSM imaging system and its performance in detail. We present dynamic measurements of neuronal morphology of neurons expressing green fluorescent protein (GFP) and GFP fusion proteins as well as functional imaging of calcium dynamics in individual dendritic spines. Although our microscope is a custom instrument, its key advantages can be easily implemented as a modification of commercial laser scanning microscopes.}, Author = {Mainen, Z. F. and Maletic-Savatic, M. and Shi, S. H. and Hayashi, Y. and Malinow, R. and Svoboda, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1046-2023}, Journal = {Methods}, Keywords = {Lasers;Fluorescent Dyes;Microscopy, Video;Animals;Synapses;In Vitro;Rats;Equipment Design;Microscopy, Confocal;Synaptic Transmission;Brain;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Recombinant Fusion Proteins;Green Fluorescent Proteins;Dissection;Dendrites;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Photons;24 Pubmed search results 2008;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {99286365}, Month = {6}, Nlm_Id = {9426302}, Number = {2}, Organization = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.}, Pages = {231-9, 181}, Pii = {S1046-2023(99)90776-4}, Pubmed = {10356355}, Title = {Two-photon imaging in living brain slices}, Uuid = {75832941-D788-40E1-ABE0-4D503019DB23}, Volume = {18}, Year = {1999}, url = {papers/Mainen_Methods1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/meth.1999.0776}} @article{Mainland:2002, Abstract = {0028-0836 Clinical Trial Controlled Clinical Trial Journal Article}, Author = {Mainland, J. D. and Bremner, E. A. and Young, N. and Johnson, B. N. and Khan, R. M. and Bensafi, M. and Sobel, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:53 -0400}, Journal = {Nature}, Keywords = {*Perception/drug effects;Human;Female;Nose/*physiology;Androstenes/administration &dosage/pharmacology;I pdf;Smell/drug effects/*physiology;Male;*Neuronal Plasticity/drug effects;13 Olfactory bulb anatomy}, Number = {6909}, Organization = {Helen Wills Neuroscience Institute, University of California at Berkeley, Berkeley, California 94720, USA. mainland\@uclink.berkeley.edu}, Pages = {802}, Title = {Olfactory plasticity: one nostril knows what the other learns}, Uuid = {00C7A6CC-39EB-47CA-8332-3CCDCD7B6478}, Volume = {419}, Year = {2002}, url = {papers/Mainland_Nature2002.pdf}} @article{Mair:1982, Abstract = {Activity was recorded from mitral cells in newborn to six-day-old rat pups during odorous stimulation. Twenty-eight neurons were studied in pups with unopened nasal cavities which sampled stimuli during intermittent periods of inhalation. Forty-six neurons were studied in pups with opened nasal cavities which were stimulated by delivering odorants directly to the olfactory epithelia. We show that mitral cells are selectively excited by different odorants on the day pups are born; prior to the maturation of bulb interneurons, the responses of neonatal mitral cells are time-locked to the inhalation cycle; neonatal mitral cells preserve the temporal patterns of activity exhibited by receptor neurons during stimulation with different concentrations of odorants; and the response patterns of mitral cells differ qualitatively between newborn and adult rats. We conclude that receptor-to-mitral cell synapses are functional in newborn rat pups and that the activity of this afferent pathway is modulated by the pups'respiratory behavior. We argue that without interneurons, mitral cells repeat the temporal code exhibited by receptor neurons and do not produce the types of response patterns characteristic of neurons in the adult rat olfactory bulb. eng Journal Article}, Author = {Mair, R. G. and Gesteland, R. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Journal = {Neuroscience}, Keywords = {Nose/physiology;Neurons/*physiology;Olfactory Bulb/cytology/*physiology;Action Potentials;Animals, Newborn/*physiology;Animal;Stimulation, Chemical;Evoked Potentials;Support, U.S. Gov't, P.H.S.;I abstr;Support, Non-U.S. Gov't;Rats/*physiology;13 Olfactory bulb anatomy}, Number = {12}, Pages = {3117-25.}, Title = {Response properties of mitral cells in the olfactory bulb of the neonatal rat}, Uuid = {7A3FF3FA-B999-4C4A-9BDF-3C461D26D328}, Volume = {7}, Year = {1982}} @article{Mair:1982a, Abstract = {Mitral cells are formed prenatally whereas most granule cells originate postnatally. Material was taken from 2-day-old, 14-day-old, 28-day-old, and adult rat olfactory bulbs and processed for rapid Golgi or Cresyl Violet staining. We show that the number of granule cell bodies/mitral cell body increases from 7.0 to 46.3 during the first two weeks of life; most mitral cells appear morphologically functional during the first postnatal week; few granule cells appear to be functional until the second postnatal week; and the number of short axon interneurons increases dramatically during the second postnatal week. We conclude the newborn rats have an intact afferent pathway from olfactory receptors to primary cortex that lacks the extensive interneuronal circuitry characteristic of adults. eng Journal Article}, Author = {Mair, R. G. and Gellman, R. L. and Gesteland, R. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Journal = {Neuroscience}, Keywords = {Granulocytes/cytology;Interneurons/cytology;Olfactory Bulb/cytology/*growth &development;Cell Division;Animal;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;I abstr;Neurons/*cytology/physiology/ultrastructure;Rats/*growth &development;13 Olfactory bulb anatomy;Animals, Newborn/*growth &development}, Number = {12}, Pages = {3105-16.}, Title = {Postnatal proliferation and maturation of olfactory bulb neurons in the rat}, Uuid = {F3EF71F9-F476-42F6-B833-D68AF851BCCF}, Volume = {7}, Year = {1982}} @article{Majed:2006, Abstract = {Microglia exist under physiological conditions in a resting state but become activated after neuronal injury. Recent studies have highlighted the reciprocal role of neurons in controlling both the number and activity of microglia. In this study, microglia derived from newborn rat cortices were cultured and activated by interferon-gamma (IFNgamma) treatment, then exposed to recombinant Sema3A or conditioned medium derived from stressed embryonic cortical neurons. We found that activation of microglia by IFNgamma induced differential upregulation of the semaphorin receptors Plexin-A1 and Neuropilin-1. This result was confirmed by Northern blotting, reverse transcription-PCR, and Western blotting. Furthermore, recombinant Sema3A induced apoptosis of microglia when added to the in vitro culture, and a similar result was obtained on activated microglia when Sema3A was produced by stressed neurons. Using an in vivo model of microglia activation by striatal injection of lipopolysaccharide demonstrated a corresponding upregulation of Plexin-A1 and Neuropilin-1 in activated microglia and enhanced production of Sema3A by stressed adult neurons. These results suggest a novel semaphorin-mediated mechanism of neuroprotection whereby stressed neurons can protect themselves from further damage by activated microglia.}, Author = {Majed, Henry H. and Chandran, Siddharthan and Niclou, Simone P. and Nicholas, Richard S. and Wilkins, Alastair and Wing, Mark G. and Rhodes, Kate E. and Spillantini, Maria Grazia and Compston, Alastair}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8102140}, Number = {6}, Organization = {Department of Clinical Neurosciences, Centre for Brain Repair, University of Cambridge, Forvie Site, Cambridge CB2 2PY, United Kingdom.}, Pages = {1730-8}, Pii = {26/6/1730}, Pubmed = {16467521}, Title = {A novel role for Sema3A in neuroprotection from injury mediated by activated microglia}, Uuid = {E3B5B916-4959-11DB-8404-000D9346EC2A}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0702-05.2006}} @article{Majewska:2006, Abstract = {Although plastic changes are known to occur in developing and adult cortex, it remains unclear whether these changes require remodeling of cortical circuitry whereby synapses are formed and eliminated or whether they rely on changes in the strength of existing synapses. To determine the structural stability of dendritic spines and axon terminals in vivo, we chose two approaches. First, we performed time-lapse two-photon imaging of dendritic spine motility of layer 5 pyramidal neurons in juvenile [postnatal day 28 (P28)] mice in visual, auditory, and somatosensory cortices. We found that there were differences in basal rates of dendritic spine motility of the same neuron type in different cortices, with visual cortex exhibiting the least structural dynamics. Rewiring visual input into the auditory cortex at birth, however, failed to alter dendritic spine motility, suggesting that structural plasticity rates might be intrinsic to the cortical region. Second, we investigated the persistence of both the presynaptic (axon terminals) and postsynaptic (dendritic spine) structures in young adult mice (P40-P61), using chronic in vivo two-photon imaging in different sensory areas. Both terminals and spines were relatively stable, with >80\%persisting over a 3 week period in all sensory regions. Axon terminals were more stable than dendritic spines. These data suggest that changes in network function during adult learning and memory might occur through changes in the strength and efficacy of existing synapses as well as some remodeling of connectivity through the loss and gain of synapses.}, Author = {Majewska, Ania K. and Newton, Jessica R. and Sur, Mriganka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't ;24 Pubmed search results 2008;Inferior Colliculus;Green Fluorescent Proteins;Auditory Pathways;Luminescent Proteins;10 Structural plasticity;10 Development;Animals;Presynaptic Terminals;Genes, Reporter;Visual Pathways;Visual Cortex;Synapses;Mice, Inbred C57BL;research support, n.i.h., extramural ;21 Circuit structure-function;Dendrites;Motion;Neuronal Plasticity;Axons;Bacterial Proteins;Learning;Auditory Cortex;Pyramidal Cells;21 Activity-development;Denervation;Geniculate Bodies;21 Neurophysiology;Microscopy, Confocal;Mice;Somatosensory Cortex;Memory;Mice, Transgenic}, Month = {3}, Nlm_Id = {8102140}, Number = {11}, Organization = {Department of Brain and Cognitive Sciences, Picower Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. ania\_majewska\@urmc.rochester.edu}, Pages = {3021-9}, Pii = {26/11/3021}, Pubmed = {16540580}, Title = {Remodeling of synaptic structure in sensory cortical areas in vivo}, Uuid = {FBE9C75E-05EB-40D2-BD0F-D690CBF97A7F}, Volume = {26}, Year = {2006}, url = {papers/Majewska_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4454-05.2006}} @article{Majewska:2000, Abstract = {We describe in detail a custom-built two-photon microscope based on a modified confocal scanhead (Olympus Fluoview) and mode-locked Ti:sapphire laser (Coherent Mira 900). This system has internal detectors as well as external whole-field detection and an electrooptical modulator for blanking the beam on flyback and effecting fast changes in excitation intensity. This microscope can be used in deep, scattering samples for quantitative measurements with a wide range of fluorophores (GFP, fura, calcium green, calcium orange, fluo-3, DiI, DiO, fluorescein, rhodamine), for fluorescent photobleaching recovery and for uncaging. Images obtained with this system can be deconvolved with the Estimation Maximization algorithm using the program XCOSM (freeware available at: http://www.ibc.wustl.edu/bcl/ xcosm/).}, Author = {Majewska, A. and Yiu, G. and Yuste, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0031-6768}, Journal = {Pflugers Arch}, Keywords = {24 Pubmed search results 2008;Dendrites;21 Neurophysiology;Photochemistry;Lasers;Software;21 Calcium imaging;Photons;Animals;Brain;Optics;Image Enhancement;Microscopy}, Medline = {21078507}, Month = {12}, Nlm_Id = {0154720}, Number = {2-3}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA. akm21\@columbia.edu}, Pages = {398-408}, Pubmed = {11211128}, Title = {A custom-made two-photon microscope and deconvolution system}, Uuid = {7436BF24-4BDA-40D1-8993-89499D4128FB}, Volume = {441}, Year = {2000}, url = {papers/Majewska_PflugersArch2000.pdf}} @article{Majewska:2006a, Abstract = {The cerebral cortex is subdivided into discrete functional areas that are defined by specific properties, including the presence of different cell types, molecular expression patterns, microcircuitry and long-range connectivity. These properties enable different areas of cortex to carry out distinct functions. Emerging data argue that the particular structure and identity of cortical areas derives not only from specific inputs but also from unique processing networks. The aim of this review is to summarize current information on the interplay of intrinsic molecular cues with activity patterns that are driven by sensory experience and shape cortical networks as they develop, emphasizing synaptic connections in networks that process vision. This review is part of the TINS special issue on The Neural Substrates of Cognition.}, Author = {Majewska, Ania K. and Sur, Mriganka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Synapses;24 Pubmed search results 2008;21 Neurophysiology;Neuronal Plasticity;Models, Neurological;21 Activity-development;21 Circuit structure-function;Nerve Net;Animals;Humans;Cerebral Cortex;review;Neurons}, Month = {6}, Nlm_Id = {7808616}, Number = {6}, Organization = {Department of Neurobiology and Anatomy, University of Rochester Medical Center, Rochester, NY 14642, USA. ania\_majewska\@urmc.rochester.edu}, Pages = {323-9}, Pii = {S0166-2236(06)00088-9}, Pubmed = {16697057}, Title = {Plasticity and specificity of cortical processing networks}, Uuid = {CCD5D401-2778-46FD-82BC-5F63F9E5E17C}, Volume = {29}, Year = {2006}, url = {papers/Majewska_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.04.002}} @article{Mak:2007, Abstract = {The regulation of female reproductive behaviors may involve memories of male pheromone signatures, formed in part by neural circuitry involving the olfactory bulb and hippocampus. These neural structures are the principal sites of adult neurogenesis; however, previous studies point to their independent regulation by sensory and physiological stimuli. Here we report that the pheromones of dominant (but not subordinate) males stimulate neuronal production in both the olfactory bulb and hippocampus of female mice, which are independently mediated by prolactin and luteinizing hormone, respectively. Neurogenesis induced by dominant-male pheromones correlates with a female preference for dominant males over subordinate males, whereas blocking neurogenesis with the mitotic inhibitor cytosine arabinoside eliminated this preference. These results suggest that male pheromones are involved in regulating neurogenesis in both the olfactory bulb and hippocampus, which may be important for female reproductive success.}, Author = {Mak, Gloria K. and Enwere, Emeka K. and Gregg, Christopher and Pakarainen, Tomi and Poutanen, Matti and Huhtaniemi, Ilpo and Weiss, Samuel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Receptors, Prolactin;Sexual Behavior, Animal;Animals;Receptors, LH;Brain;Female;Mice, Inbred C57BL;research support, non-u.s. gov't;Behavior, Animal;Cell Proliferation;Immunosuppressive Agents;Mice, Inbred ICR;Male;Cytarabine;In Situ Nick-End Labeling;Mice, Knockout;Neurons;Sex Attractants;Social Dominance;Zinc Sulfate;Mice;24 Pubmed search results 2008;Bromodeoxyuridine;Nerve Tissue Proteins;Astringents}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Hotchkiss Brain Institute, Department of Cell Biology & Anatomy, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada.}, Pages = {1003-11}, Pii = {nn1928}, Pubmed = {17603480}, Title = {Male pheromone-stimulated neurogenesis in the adult female brain: possible role in mating behavior}, Uuid = {98853858-5A97-4F01-A8CD-2B62468B859D}, Volume = {10}, Year = {2007}, url = {papers/Mak_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1928}} @article{Makar:2002, Abstract = {The peripheral delivery of interferon-beta (IFN-beta) for the treatment of central nervous system (CNS) diseases is only partially effective because of the blood-brain barrier (BBB). To circumvent this problem, we evaluated the feasibility of genetically altering bone marrow cells ex vivo and using them as vehicles to transfer the IFN-beta cDNA into the mouse CNS. An IFN-beta retroviral expression vector (pLXSN-IFNbeta) was used to stably transfect PA317 cells. The supernatant from these producer cells, which expressed IFN-beta mRNA and protein, were used to infect bone marrow cells. When transplanted into irradiated mice, IFN-beta-engineered marrow cells accessed the CNS and expressed IFN-beta mRNA and protein. Marrow cells transduced with a control neomycin vector entered the brain and expressed the neomycin but not the IFN-beta gene. In the CNS, IFN-beta delivered by marrow cells induced the mRNA expression of 2',5'-oligoadenylate synthetase (2',5'-OAS), indicating biologic activity. Our findings demonstrating that bone marrow cells can serve as a delivery system for IFN-beta cDNA into the CNS could have implications for the treatment of neurologic disorders, such as multiple sclerosis (MS), viral encephalitis, and brain tumors.}, Author = {Makar, Tapas Kumar and Wilt, Susan and Dong, Zhongyun and Fishman, Paul and Mouradian, M. Maral and Dhib-Jalbut, Suhayl}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1079-9907}, Journal = {J Interferon Cytokine Res}, Keywords = {Animals;Feasibility Studies;Transfection;Bone Marrow Transplantation;Research Support, U.S. Gov't, Non-P.H.S.;Brain;Enzyme Induction;Kanamycin Kinase;Specific Pathogen-Free Organisms;2',5'-Oligoadenylate Synthetase;Recombinant Fusion Proteins;Blood-Brain Barrier;Genes, Synthetic;11 Glia;Research Support, U.S. Gov't, P.H.S.;RNA, Messenger;Genetic Vectors;Gene Therapy;DNA, Complementary;Mice;Genes, Reporter;Interferon-beta;Research Support, Non-U.S. Gov't}, Medline = {22172979}, Month = {7}, Nlm_Id = {9507088}, Number = {7}, Organization = {Department of Neurology, University of Maryland, and Department of Veterans Affairs, Baltimore, MD 21201, USA.}, Pages = {783-91}, Pubmed = {12184916}, Title = {IFN-beta gene transfer into the central nervous system using bone marrow cells as a delivery system}, Uuid = {4620A9EC-1589-4012-A77F-FA327B9893BA}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/107999002320271378}} @article{Makranz:2004, Abstract = {Complement-receptor-3 (CR3/MAC-1), scavenger-receptor-AI/II (SRAI/II) and Fcgamma-receptor (FcgammaR) can mediate phagocytosis of degenerated myelin in macrophages and microglia. However, CR3/MAC-1 and SRAI/II, but not FcgammaR, mediate phagocytosis after axonal injury. We tested for phosphatidylinositol 3-kinase (PI3K), phosphoinositide-specific phospholipase-Cgamma (PLCgamma) and protein kinase-C (PKC) signaling in myelin phagocytosis mediated by CR3/MAC-1 alone and by CR3/MAC-1 combined with SRAI/II. Phagocytosis was inhibited by PI3K inhibitors wortmannin and LY-294002, PLCgamma inhibitor U-73122, classical PKC (cPKC) inhibitor Go-6976, general PKC inhibitors Ro-318220 and calphostin-C, and BAPTA/AM which chelates intracellular Ca(2+) required for cPKC activation. PKC activator PMA augmented phagocytosis and further alleviated inhibitions induced by PI3K and PLCgamma inhibitors. Overall, altering PKC activity modulated phagocytosis 4- to 6-fold between inhibition and augmentation. PLCgamma activation did not require tyrosine phosphorylation. Thus, signaling of myelin phagocytosis mediated by CR3/MAC-1 alone and by CR3/MAC-1 combined with SRAI/II involves PI3K, PLCgamma and cPKC, the cascade PI3K-->PLCgamma-->cPKC, and wide-range modulation by PKC. This pathway may thus be targeted for in vivo modulation, which may explain differences in the efficiency of CR3/MAC-1-mediated myelin phagocytosis in different pathological conditions.}, Author = {Makranz, Chen and Cohen, Goni and Baron, Ayellet and Levidor, Lital and Kodama, Tatsuhiko and Reichert, Fanny and Rotshenker, Shlomo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0969-9961}, Journal = {Neurobiol Dis}, Keywords = {Mice, Inbred BALB C;Signal Transduction;Protein Kinase C;Nerve Degeneration;Myelin Sheath;Protein Subunits;Macrophages;Enzyme Inhibitors;Animals;Phosphorylation;Phagocytosis;Axons;Cell Line, Tumor;Phospholipase C;Not relevant;11 Glia;1-Phosphatidylinositol 3-Kinase;Nerve Regeneration;Chelating Agents;Support, Non-U.S. Gov't;Macrophage-1 Antigen;Mice, Knockout;Antigens, CD36;Mice;Demyelinating Diseases}, Month = {3}, Nlm_Id = {9500169}, Number = {2}, Organization = {Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School and the Eric Roland Center for Neurodegenerative Diseases, Jerusalem, Israel.}, Pages = {279-86}, Pii = {S0969996103002456}, Pubmed = {15006698}, Title = {Phosphatidylinositol 3-kinase, phosphoinositide-specific phospholipase-Cgamma and protein kinase-C signal myelin phagocytosis mediated by complement receptor-3 alone and combined with scavenger receptor-AI/II in macrophages}, Uuid = {A134BE99-4BE7-424E-BBF1-A5EB194051CD}, Volume = {15}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.nbd.2003.11.007}} @article{Malatesta:2000, Abstract = {The developing central nervous system of vertebrates contains an abundant cell type designated radial glial cells. These cells are known as guiding cables for migrating neurons, while their role as precursor cells is less clear. Since radial glial cells express a variety of astroglial characteristics and differentiate as astrocytes after completing their guidance function, they have been considered as part of the glial lineage. Using fluorescence-activated cell sorting, we show here that radial glial cells also are neuronal precursors and only later, after neurogenesis, do they shift towards an exclusive generation of astrocytes. These results thus demonstrate a novel function for radial glial cells, namely their ability to generate two major cell types found in the nervous system, neurons and astrocytes.}, Author = {Malatesta, P. and Hartfuss, E. and G{\"o}tz, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Glial Fibrillary Acidic Protein;Cell Differentiation;Animals;Astrocytes;Cell Separation;Rats;Recombinant Proteins;Mice, Transgenic;ATP-Binding Cassette Transporters;Rats, Wistar;Mice, Inbred C57BL;Green Fluorescent Proteins;Amino Acid Transport System X-AG;Male;Cerebral Cortex;Neurons;Neuroglia;Flow Cytometry;Promoter Regions (Genetics);Mice;Luminescent Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {20530480}, Month = {12}, Nlm_Id = {8701744}, Number = {24}, Organization = {Max-Planck Institute of Neurobiology, Am Klopferspitz 18A, D-82152 Planegg-Martinsried, Germany.}, Pages = {5253-63}, Pubmed = {11076748}, Title = {Isolation of radial glial cells by fluorescent-activated cell sorting reveals a neuronal lineage}, Uuid = {AE860997-71C2-11DA-A383-000D9346EC2A}, Volume = {127}, Year = {2000}, url = {papers/Malatesta_Development2000.pdf}} @article{Malatesta:2003, Abstract = {The precursor function of the ubiquitous glial cell type in the developing central nervous system (CNS), the radial glia, is largely unknown. Using Cre/loxP in vivo fate mapping studies, we found that radial glia generate virtually all cortical projection neurons but not the interneurons originating in the ventral telencephalon. In contrast to the cerebral cortex, few neurons in the basal ganglia originate from radial glia, and in vitro lineage analysis revealed intrinsic differences in the potential of radial glia from the dorsal and ventral telencephalon. This shows that the progeny of radial glia not only differs profoundly between brain regions but also includes the majority of neurons in some parts of the CNS. 22516608 0896-6273 Journal Article}, Author = {Malatesta, P. and Hack, M. A. and Hartfuss, E. and Kettenmann, H. and Klinkert, W. and Kirchhoff, F. and Gotz, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Neuron}, Keywords = {10 Development;Integrase/analysis/biosynthesis/genetics;Glial Fibrillary Acidic Protein/analysis/biosynthesis/genetics;Neural Pathways/chemistry/embryology/growth &development/metabolism;Cerebral Cortex/chemistry/embryology/growth &development/metabolism;Neurons/*chemistry/physiology;Viral Proteins/analysis/biosynthesis/genetics;Mice, Inbred C57BL;Animal;Mice, Transgenic;F;Neuroglia/*chemistry/physiology;Cells, Cultured;Support, Non-U.S. Gov't;Mice;Basal Ganglia/chemistry/embryology/growth &development/metabolism}, Number = {5}, Organization = {Max-Planck Institute of Neurobiology, Am Klopferspitz 18A, D-82152 Planegg-Martinsried, Germany.}, Pages = {751-64}, Pubmed = {12628166}, Title = {Neuronal or glial progeny: regional differences in radial glia fate}, Uuid = {74035A95-54E7-4E61-9700-E2ADDCAB33FC}, Volume = {37}, Year = {2003}, url = {papers/Malatesta_Neuron2003.pdf}} @article{Male:2001, Author = {Male, D. and Rezaie, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0079-6123}, Journal = {Prog Brain Res}, Keywords = {Central Nervous System;Cell Adhesion Molecules;Stem Cells;Chemokines;11 Glia;Microglia;review, tutorial;Blood Vessels;Animals;Humans;review}, Medline = {21428568}, Nlm_Id = {0376441}, Organization = {Immunology Section, Department of Biological Sciences, Open University, Milton Keynes MK7 6AA, UK. d.k.male\@open.ac.uk}, Pages = {81-93}, Pubmed = {11545033}, Title = {Colonisation of the human central nervous system by microglia: the roles of chemokines and vascular adhesion molecules}, Uuid = {BA6DC32A-F039-48D7-AB1C-F187DECA5CE2}, Volume = {132}, Year = {2001}} @article{Maletic-Savatic:1995, Abstract = {Hippocampal neurons are highly plastic in their excitable properties, both during development and in the adult brain. As voltage-sensitive K+ channels are major determinants of membrane excitability, one mechanism for generating plasticity is through regulation of K+ channel activity. To gain insights into the regulation of K+ channels in the hippocampus, we have analyzed the spatiotemporal expression patterns of five K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro. Delayed rectifier-type channels (Kv1.5, Kv2.1, and Kv2.2) are expressed on all neuronal somata and proximal dendrites, while A-type channels (Kv1.4 and Kv4.2) are present distally on distinct subpopulations of neurons. The development of these patterns in situ is monotonic; that is, while the time and spatial development varies among the channels, each K+ channel subtype initially appears in its adult pattern, suggesting that the mechanisms underlying spatial patterning operate through development. Immunoblots confirm the differential temporal expression of K+ channels in the developing hippocampus, and demonstrate developmentally regulated changes in the microheterogeneity of some K+ channel polypeptide species. Temporal expression patterns of all five K+ channels observed in situ are retained in vitro, while certain aspects of cellular and subcellular localization are altered for some of the K+ channel polypeptides studied. Similarities in K+ channel polypeptide expression in situ and in vitro indicate that the same regulatory mechanisms are controlling spatiotemporal patterning in both situations. However, differences between levels of expression for all subtypes studied except Kv2.1 indicate additional mechanisms operating in situ but absent in vitro that are important in determining polypeptide abundance.}, Author = {Maletic-Savatic, M. and Lenn, N. J. and Trimmer, J. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:53 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Fetus;13 Olfactory bulb anatomy;Electrophoresis, Polyacrylamide Gel;Animals;In Vitro;Cells, Cultured;Aging;Rats;Comparative Study;Cell Membrane;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Immunoblotting;Dendrites;Animals, Newborn;Support, Non-U.S. Gov't;Potassium Channels;Neurons;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Gene Expression}, Medline = {95271336}, Month = {5}, Nlm_Id = {8102140}, Number = {5 Pt 2}, Organization = {Department of Neurology, State University of New York, Stony Brook, New York 11794, USA.}, Pages = {3840-51}, Pubmed = {7751950}, Title = {Differential spatiotemporal expression of K+ channel polypeptides in rat hippocampal neurons developing in situ and in vitro}, Uuid = {A54A7FD3-F248-4FB5-86E6-2B20CF31EACC}, Volume = {15}, Year = {1995}, url = {papers/Maletic-Savatic_JNeurosci1995.pdf}} @article{Malik:1995, Abstract = {Gene transfer into human hematopoietic stem cells with expression targeted to the maturing myelomonocytic progeny has applications for gene therapy of genetic diseases affecting granulocytes and macrophages. We hypothesized that promoters of myeloid-specific genes that are upregulated with myelomonocytic differentiation would also upregulate expression of an exogenous gene in a retroviral vector. Moloney murine leukemia virus (MoMuLV)-based retroviral vectors using promoters from hematopoietic genes (CD11b, CD18, and CD34) were compared with vectors with viral promoters (MoMuLV long terminal repeat [LTR], cytomegalovirus [CMV], and simian virus 40 [SV40]). Human glucocerebrosidase (GC) cDNA was the reporter gene. HL60 cells were transduced with these vectors and vector-derived GC activity was compared in undifferentiated HL-60 cells and the same cells differentiated into granulocytes using dimethyl sulfoxide or monocyte/macrophages using phorbol myristate acetate. In undifferentiated HL-60 cells, vector-derived GC activity was the highest when it was controlled by the MoMuLV LTR. In HL-60 cells differentiated into granulocytes, vector-derived GC activity transcribed from the CD11b, MoMuLV LTR, and CMV promoters was equivalent to 1.7, 1.5, and 1.5 times the normal endogenous GC activity, respectively, and 0.8, 2.0, and 3.6 times the normal GC activity, respectively, in those differentiated into macrophages. With granulocytic differentiation, the CD11b promoter showed maximal induction in GC activity (8-fold); with macrophage differentiation, the CD11b promoter showed a fourfold induction in GC expression. The CD11b promoter also generated significant levels of GC activity in the myelomonocytic progeny of transduced CD34+ cells. Expression from the CD11b promoter, unlike that from the CMV or the MoMuLV LTR promoters, was relatively myelomonocyte-specific, with minimal expression observed in Jurkat T cells or HeLa carcinoma cells. The induction of expression from the CD11b promoter with differentiation in HL-60 cells correlates with the developmental regulation of the CD11b gene. Retroviral vectors using the CD11b promoter have potential utility for gene therapy of disorders affecting the myelomonocytic lineage. 0006-4971 Journal Article}, Author = {Malik, P. and Krall, W. J. and Yu, X. J. and Zhou, C. and Kohn, D. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Blood}, Keywords = {*Genetic Vectors;Human;Cell Differentiation;DNA, Complementary/genetics;T-Lymphocytes/drug effects;Glucosylceramidase/genetics;Leukemia, T-Cell, Acute;Repetitive Sequences, Nucleic Acid;*Gene Expression Regulation, Neoplastic;Macrophage-1 Antigen/*genetics;Moloney murine leukemia virus/*genetics;*Promoter Regions (Genetics);EE, DMSO, abstr;08 Aberrant cell cycle;Hematopoietic Stem Cells/*metabolism;Antigens, CD34/*genetics;Recombinant Fusion Proteins/biosynthesis;Dimethyl Sulfoxide/pharmacology;Hela Cells/drug effects;Support, Non-U.S. Gov't;*Gene Transfer Techniques;Organ Specificity;Tumor Cells, Cultured;Support, U.S. Gov't, P.H.S.;HL-60 Cells/drug effects;Tetradecanoylphorbol Acetate/pharmacology;Genes, Reporter;Antigens, CD18/*genetics}, Number = {8}, Organization = {Division of Research Immunology/Bone Marrow Transplantation, Childrens Hospital, Los Angeles, University of Southern California School of Medicine, USA.}, Pages = {2993-3005}, Pubmed = {7579392}, Title = {Retroviral-mediated gene expression in human myelomonocytic cells: a comparison of hematopoietic cell promoters to viral promoters}, Uuid = {717F1A5D-6A3A-4ECE-9EB6-F4EE62689F8E}, Volume = {86}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7579392}} @article{Mallamaci:2006, Abstract = {Early thalamus-independent steps in the process of cortical arealization take place on the basis of information intrinsic to the cortical primordium, as proposed by Rakic in his classical protomap hypothesis [Rakic, P. (1988)Science, 241, 170-176]. These steps depend on a dense network of molecular interactions, involving genes encoding for diffusible ligands which are released around the borders of the cortical field, and transcription factor genes which are expressed in graded ways throughout this field. In recent years, several labs worldwide have put considerable effort into identifying members of this network and disentangling its topology. In this respect, a considerable amount of knowledge has accumulated and a first, provisional description of the network can be delineated. The aim of this review is to provide an organic synthesis of our current knowledge of molecular genetics of early cortical arealization, i.e. to summarise the mechanisms by which secreted ligands and graded transcription factor genes elaborate positional information and trigger the activation of distinctive area-specific morphogenetic programs.}, Author = {Mallamaci, Antonello and Stoykova, Anastassia}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {21 Epilepsy;24 Pubmed search results 2008;Gene Expression Regulation, Developmental;Research Support, Non-U.S. Gov't;Ligands;21 Neurophysiology;Genes, Regulator;Neural Pathways;Body Patterning;Animals;Humans;Cerebral Cortex;review;Transcription Factors}, Month = {2}, Nlm_Id = {8918110}, Number = {4}, Organization = {DIBIT, Unit of Cerebral Cortex Development, Department of Molecular Biology and Functional Genomics, San Raffaele Scientific Intitute, via Olgettina 58, 20132 Milan, Italy. a.mallamaci\@hsr.it}, Pages = {847-56}, Pii = {EJN4634}, Pubmed = {16519650}, Title = {Gene networks controlling early cerebral cortex arealization}, Uuid = {2929E8A4-DAD9-4782-BC58-FA87FA94E4CA}, Volume = {23}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.04634.x}} @article{Mallat:2005, Abstract = {Cell corpses generated during CNS development are eliminated through phagocytosis performed by a variety of cells, including mesenchyme-derived macrophages and microglia, or glial cells originating in the neurogenic ectoderm. Mounting evidence indicates that in different species, phagocytes not only clear cell corpses but also engulf still-living neural cells or axons, and thereby promote cell death or axon pruning. Knowledge of the mechanisms of corpse recognition by engulfing cells provides molecular signals to this new role for phagocytes. These observations support a conserved and instructive role for phagocytosis in the execution of regressive events during neurogenesis.}, Author = {Mallat, Michel and Mar{\'\i}n-Teva, Jos{\'e} Luis and Ch{\'e}ret, Cyril}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Central Nervous System;Apoptosis;11 Glia;Humans;Animals;Phagocytosis;review;Neurons}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Biologie des Interactions Neurone-glie, INSERM U.495, IFR 70, UPMC, H\^{o}pital de la Salp\^{e}tri\`{e}re, 47 boulevard de l'H\^{o}pital, 75013 Paris, France. michel.mallat\@infobiogen.fr}, Pages = {101-7}, Pii = {S0959-4388(05)00007-3}, Pubmed = {15721751}, Title = {Phagocytosis in the developing CNS: more than clearing the corpses}, Uuid = {BCEDC80F-00B3-11DB-9E68-000D9346EC2A}, Volume = {15}, Year = {2005}, url = {papers/Mallat_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.01.006}} @article{Manaka:1972, Author = {Manaka, S. and Sato, S. and Fuchinoue, T. and Sekino, H. and Nagai, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0006-8969}, Journal = {No To Shinkei}, Keywords = {Epilepsy;Electroencephalography;Adult;Female;Humans;Psychosurgery;Brain}, Medline = {72145055}, Month = {3}, Nlm_Id = {0413550}, Number = {3}, Pages = {311-8}, Pubmed = {5067047}, Title = {[Successfully treated case of ectopic gray matter as a cause of uncontrollable epilepsy]}, Uuid = {961AF4BA-4963-4F38-BE45-5B27B9BAA9F4}, Volume = {14}, Year = {1972}} @article{Mancilla:2007, Abstract = {We performed a systematic analysis of phase locking in pairs of electrically coupled neocortical fast-spiking (FS) and low-threshold-spiking (LTS) interneurons and in a conductance-based model of a pair of FS cells. Phase-response curves (PRCs) were obtained for real interneurons and the model cells. We used PRCs and the theory of weakly coupled oscillators to make predictions about phase-locking characteristics of cell pairs. Phase locking and the robustness of phase-locked states to differences in intrinsic frequencies of cells were directly examined by driving interneuron pairs through a wide range of firing frequencies. Calculations using PRCs accurately predicted that electrical coupling robustly synchronized the firing of interneurons over all frequencies studied (FS, approximately 25-80 Hz; LTS, approximately 10-30 Hz). The synchronizing ability of electrical coupling and the robustness of the phase-locked states were directly dependent on the strength of coupling but not on firing frequency. The FS cell model also predicted the existence of stable antiphase firing at frequencies below approximately 30 Hz, but no evidence for stable antiphase firing was found using the experimentally determined PRCs or in direct measures of phase locking in pairs of interneurons. Despite significant differences in biophysical properties of FS and LTS cells, their phase-locking behavior was remarkably similar. The wide spikes and shallow action potential afterhyperpolarizations of interneurons, compared with the model, prohibited antiphase behavior. Electrical coupling between cortical interneurons of the same type maintained robust synchronous firing of cell pairs for up to approximately 10\%heterogeneity in their intrinsic frequencies.}, Author = {Mancilla, Jaime G. and Lewis, Timothy J. and Pinto, David J. and Rinzel, John and Connors, Barry W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8102140}, Number = {8}, Organization = {Department of Neuroscience, Division of Biology and Medicine, Brown University, Providence, Rhode Island 02912, USA. mancilla\@email.unc.edu}, Pages = {2058-73}, Pii = {27/8/2058}, Pubmed = {17314301}, Title = {Synchronization of electrically coupled pairs of inhibitory interneurons in neocortex}, Uuid = {49B904BB-F38A-4BEC-BA7D-7066B9620EEB}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2715-06.2007}} @article{Mander:2006, Abstract = {Microglia are resident brain macrophages that become activated and proliferate following brain damage or stimulation by immune mediators, such as IL-1beta or TNF-alpha. We investigated the mechanisms by which microglial proliferation is regulated in primary cultures of rat glia. We found that basal proliferation of microglia was stimulated by proinflammatory cytokines IL-1beta or TNF-alpha, and this proliferation was completely inhibited by catalase, implicating hydrogen peroxide as a mediator of proliferation. In addition, inhibitors of NADPH oxidase (diphenylene iodonium or apocynin) also prevented microglia proliferation, suggesting that this may be the source of hydrogen peroxide. IL-1beta and TNF-alpha rapidly stimulated the rate of hydrogen peroxide produced by isolated microglia, and this was inhibited by diphenylene iodonium, implying that the cytokines were acting directly on microglia to stimulate the NADPH oxidase. Low concentrations of PMA or arachidonic acid (known activators of NADPH oxidase) or xanthine/xanthine oxidase or glucose oxidase (generating hydrogen peroxide) also increased microglia proliferation and this was blocked by catalase, showing that NADPH oxidase activation or hydrogen peroxide was sufficient to stimulate microglia proliferation. In contrast to microglia, the proliferation of astrocytes was unaffected by the presence of catalase. In conclusion, these findings indicate that microglial proliferation in response to IL-1beta or TNF-alpha is mediated by hydrogen peroxide from NADPH oxidase.}, Author = {Mander, Palwinder K. and Jekabsone, Aiste and Brown, Guy C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {2985117R}, Number = {2}, Organization = {Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.}, Pages = {1046-52}, Pii = {176/2/1046}, Pubmed = {16393992}, Title = {Microglia proliferation is regulated by hydrogen peroxide from NADPH oxidase}, Uuid = {D934E02E-901F-4BCB-B24E-9AB58C5542D8}, Volume = {176}, Year = {2006}} @article{Manent:2005, Abstract = {Immature neurons express GABA and glutamate receptors before synapse formation, and both transmitters are released at an early developmental stage. We have now tested the hypothesis that the ongoing release of GABA and glutamate modulates neuronal migration. Using 5-bromo-2'-deoxyuridine labeling and cocultures of hippocampal slices obtained from naive and green fluorescent protein-transgenic mice, we report that migration is severely affected by GABA(A) or NMDA receptor antagonist treatments. These effects were also present in munc18-1 knock-out slices in which soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-dependent vesicular secretion of transmitters has been deleted. GABA(A) antagonists were more efficient than NMDA antagonists to reduce cell migration, in keeping with the earlier maturation of GABAergic mechanisms. We conclude that GABA and, to a lesser degree, glutamate released in a SNARE-independent mechanism exert a paracrine action on neuronal migration.}, Author = {Manent, Jean-Bernard B. and Demarque, Micha{\"e}l and Jorquera, Isabel and Pellegrino, Christophe and Ben-Ari, Yehezkel and Aniksztejn, Laurent and Represa, Alfonso}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {5}, Nlm_Id = {8102140}, Number = {19}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U29, Campus de Luminy BP13, 13273 Marseille, France.}, Pages = {4755-65}, Pii = {25/19/4755}, Pubmed = {15888651}, Title = {A noncanonical release of GABA and glutamate modulates neuronal migration}, Uuid = {49CD7728-F069-4245-AD90-345FD45DE081}, Volume = {25}, Year = {2005}, url = {papers/Manent_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0553-05.2005}} @article{Manent:2006, Abstract = {Paracrine GABA and glutamate acting, respectively, on GABAA and NMDA receptors modulate the migration of hippocampal pyramidal cells. Using corticohippocampal organotypic explants from glutamic acid decarboxylase (GAD) 67-enhanced green fluorescent protein (EGFP) knock-in embryos, we now report that, in contrast to pyramidal neurons, the blockade of AMPA but not NMDA receptors exerts important actions on the migration of GABAergic interneurons. In addition, the blockade of GABAA receptors fails to modify the migration rates of GABAergic interneurons. Immunohistochemical analyses of GAD67-EGFP embryos (from embryonic day 14 to birth) reveal that interneurons colonize the hippocampal primordium by embryonic day 15. At that stage, the hippocampal primordium is already composed of pioneer glutamatergic neurons, including (1) Cajal-Retzius cells, immunopositive to calretinin and reelin, and (2) other presumptive pioneer pyramidal cells that are immunopositive to betaIII-tubulin and vesicular glutamate transporter 3 and immunonegative to GABA or GAD67. Therefore, the migrations of pyramidal neurons and GABAergic interneurons are cross-modulated: glutamate released from pioneer glutamatergic neurons facilitates the migration of GABAergic interneurons, which in turn would release GABA, facilitating the migration of glutamatergic neuroblasts. This general sequence may provide a retroactive positive loop needed to construct the hippocampal network. It might constitute a primitive homeostatic mechanism in the developing brain that acts to balance GABA-glutamate contributions to network construction and activity.}, Author = {Manent, Jean-Bernard B. and Jorquera, Isabel and Ben-Ari, Yehezkel and Aniksztejn, Laurent and Represa, Alfonso}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Pregnancy;Animals;In Vitro;Glutamic Acid;21 Epilepsy;Female;Cell Movement;Mice, Transgenic;Embryonic Development;Hippocampus;Receptors, AMPA;Green Fluorescent Proteins;Cerebral Cortex;21 Neurophysiology;Mice;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;Interneurons;Receptors, N-Methyl-D-Aspartate;12 Interneuron development;Research Support, Non-U.S. Gov't}, Month = {5}, Nlm_Id = {8102140}, Number = {22}, Organization = {Institut de Neurobiologie de la M{\'e}diterran{\'e}e, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, Unit{\'e} 29, 13273 Marseille, France.}, Pages = {5901-9}, Pii = {26/22/5901}, Pubmed = {16738232}, Title = {Glutamate acting on AMPA but not NMDA receptors modulates the migration of hippocampal interneurons}, Uuid = {185ED19E-1324-48B0-83C5-F9465745C821}, Volume = {26}, Year = {2006}, url = {papers/Manent_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1033-06.2006}} @article{Manev:2001, Abstract = {5-Lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) are two enzymes that are critical for the synthesis of eicosanoids, the inflammatory metabolites of arachidonic acid. Both 5-LOX and COX-2 are expressed in the brain, including in CNS neurons. The physiologic role of these proteins in neuronal functioning is not clear. In non-neuronal tissues these two enzymes often assume similar roles: in addition to their function in inflammation, 5-LOX and COX-2 appear to be associated with cell proliferation, that is, with tumor growth. High 5-LOX expression has been noticed in the proliferating brain or pancreatic tumor cells; reduction in tumor cell proliferation and/or destruction of tumor cells was achieved with 5-LOX inhibitors. Proliferation of immature neurons/neuroblasts is an important component of mitotic neurogenesis. We investigated the role of 5-LOX in proliferation using cultures of human neuronal precursor cells, NT2. We found that these cells express 5-LOX mRNA and we used 3H-thymidine incorporation as a measure of cell proliferation; this was reduced by treating the cultures with 5-LOX inhibitor AA-861. We propose that the 5-LOX pathway plays a crucial role in mitotic neurogenesis. Additional studies should explore whether 5-LOX may participate in neurogenesis related pathologies and whether it should be considered a target for procedures aimed at altering neurogenesis for therapeutic purposes. eng Journal Article}, Author = {Manev, H. and Uz, T. and Manev, R. and Zhang, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Journal = {Ann N Y Acad Sci}, Keywords = {Neurons/*drug effects/*physiology;Neuroprotective Agents/metabolism;Human;Cell Line;Lipoxygenase Inhibitors/*pharmacology;Animal;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Benzoquinones/*pharmacology;Arachidonate 5-Lipoxygenase/*drug effects/metabolism;RNA, Messenger/drug effects/metabolism;C abstr}, Organization = {Psychiatric Institute, Department of Psychiatry, University of Illinois at Chicago, 1601 West Taylor Street, MC912, Chicago, IL 60612, USA. HManev\@psych.uic.edu}, Pages = {45-51.}, Title = {Neurogenesis and neuroprotection in the adult brain. A putative role for 5-lipoxygenase?}, Uuid = {E587D2AD-CAC9-4DDD-8D46-7417BBE6D5DF}, Volume = {939}, Year = {2001}} @article{Manfra:2001, Abstract = {Transgenic mice expressing green fluorescent protein (GFP) were generated to provide a source of labeled leukocytes for cell transfer studies. The transgene comprises the GFP coding region under the transcriptional control of the chicken ss-actin promoter and human cytomegalovirus enhancer. Mice expressing this GFP transgene were generated in the B6D2 and in the 129SvEv backgrounds. Flow cytometric analysis of cells from the blood, spleen, and bone marrow of these transgenic mice revealed that most leukocytes, including dendritic cells and memory T cells, express GFP. In allogeneic cell transfers, donor GFP+ splenocytes were detected in the spleen and mesenteric lymph nodes of recipient mice within 2 hours after transfer and for at least 9 days thereafter. In syngeneic experiments using 129-derived GFP+ donor splenocytes, donor cells were detected in multiple tissues of 129 recipients from 2 hours to 3 weeks after transfer. In bone-marrow transplantation experiments using irradiated allogeneic recipients, the percent of GFP+ donor cells in recipients at 3 weeks was comparable to that seen in similar tissues of GFP+ donor mice. These data demonstrate that GFP+ transgenic mice provide a ready source of GFP-expressing primary cells that can be easily monitored after their transfer to recipient animals.}, Author = {Manfra, D. J. and Chen, S. C. and Yang, T. Y. and Sullivan, L. and Wiekowski, M. T. and Abbondanzo, S. and Vassileva, G. and Zalamea, P. and Cook, D. N. and Lira, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Animals;Bone Marrow Transplantation;Female;Mice, Transgenic;Adoptive Transfer;Recombinant Fusion Proteins;Mice, Inbred C57BL;11 Glia;Microscopy, Fluorescence;Green Fluorescent Proteins;Male;Bone Marrow Cells;Mice, Inbred Strains;Leukocytes;Mice, Inbred DBA;Mice;Luminescent Proteins;Gene Expression;Spleen}, Medline = {20580890}, Month = {1}, Nlm_Id = {0370502}, Number = {1}, Organization = {Department of Immunology, Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.}, Pages = {41-7}, Pubmed = {11141477}, Title = {Leukocytes expressing green fluorescent protein as novel reagents for adoptive cell transfer and bone marrow transplantation studies}, Uuid = {2CD570BE-2F25-4B16-9410-E50C1F107499}, Volume = {158}, Year = {2001}} @article{Mangale:2008, Abstract = {The earliest step in creating the cerebral cortex is the specification of neuroepithelium to a cortical fate. Using mouse genetic mosaics and timed inactivations, we demonstrated that Lhx2 acts as a classic selector gene and essential intrinsic determinant of cortical identity. Lhx2 selector activity is restricted to an early critical period when stem cells comprise the cortical neuroepithelium, where it acts cell-autonomously to specify cortical identity and suppress alternative fates in a spatially dependent manner. Laterally, Lhx2 null cells adopt antihem identity, whereas medially they become cortical hem cells, which can induce and organize ectopic hippocampal fields. In addition to providing functional evidence for Lhx2 selector activity, these findings show that the cortical hem is a hippocampal organizer.}, Author = {Mangale, Vishakha S. and Hirokawa, Karla E. and Satyaki, Prasad R. V. and Gokulchandran, Nandini and Chikbire, Satyadeep and Subramanian, Lakshmi and Shetty, Ashwin S. and Martynoga, Ben and Paul, Jolly and Mai, Mark V. and Li, Yuqing and Flanagan, Lisa A. and Tole, Shubha and Monuki, Edwin S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {10 Development;Embryonic Induction;Animals;Transcription Factors;Gene Expression Regulation, Developmental;Chimera;Epithelium;Homeodomain Proteins;Mutation;Telencephalon;Hippocampus;Pyramidal Cells;Neuroepithelial Cells;research support, non-u.s. gov't;Organizers, Embryonic;Prosencephalon;Embryonic Stem Cells;10 genetics malformation;Cerebral Cortex;Mice, Knockout;Cell Aggregation;Dentate Gyrus;Recombination, Genetic;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008}, Mid = {UKMS1965}, Month = {1}, Nlm_Id = {0404511}, Number = {5861}, Organization = {Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai 400005, India.}, Pages = {304-9}, Pii = {319/5861/304}, Pmc = {PMC2494603}, Pubmed = {18202285}, Title = {Lhx2 selector activity specifies cortical identity and suppresses hippocampal organizer fate}, Uuid = {1D3F8C0E-E5F7-4492-B285-5EA34C534417}, Volume = {319}, Year = {2008}, url = {papers/Mangale_Science2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1151695}} @article{Manganas:2007, Abstract = {The identification of neural stem and progenitor cells (NPCs) by in vivo brain imaging could have important implications for diagnostic, prognostic, and therapeutic purposes. We describe a metabolic biomarker for the detection and quantification of NPCs in the human brain in vivo. We used proton nuclear magnetic resonance spectroscopy to identify and characterize a biomarker in which NPCs are enriched and demonstrated its use as a reference for monitoring neurogenesis. To detect low concentrations of NPCs in vivo, we developed a signal processing method that enabled the use of magnetic resonance spectroscopy for the analysis of the NPC biomarker in both the rodent brain and the hippocampus of live humans. Our findings thus open the possibility of investigating the role of NPCs and neurogenesis in a wide variety of human brain disorders.}, Author = {Manganas, Louis N. and Zhang, Xueying and Li, Yao and Hazel, Raphael D. and Smith, S. David and Wagshul, Mark E. and Henn, Fritz and Benveniste, Helene and Djuric, Petar M. and Enikolopov, Grigori and Maletic-Savatic, Mirjana}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Cell Differentiation;Animals;Humans;Signal Processing, Computer-Assisted;Rats;Algorithms;Brain;Adult Stem Cells;Female;Child;Hippocampus;research support, non-u.s. gov't;Male;Embryonic Stem Cells;Brain Chemistry;Magnetic Resonance Spectroscopy;Neurons;Fatty Acids;Adult;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Biological Markers;Stem Cells;research support, u.s. gov't, non-p.h.s.;Protons;Adolescent}, Month = {11}, Nlm_Id = {0404511}, Number = {5852}, Organization = {SUNY Stony Brook, Stony Brook, NY 11794, USA.}, Pages = {980-5}, Pii = {318/5852/980}, Pubmed = {17991865}, Title = {Magnetic resonance spectroscopy identifies neural progenitor cells in the live human brain}, Uuid = {973E3224-E7DB-4537-B879-672D758038D3}, Volume = {318}, Year = {2007}, url = {papers/Manganas_Science2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1147851}} @article{Manger:2002, Abstract = {We describe representations of the visual field in areas 18, 19 and 21 of the ferret using standard microelectrode mapping techniques. In all areas the azimuths are represented as islands of peripheral visual field surrounded by central visual field representation. The zero meridian was found at the 17/18 and 19/21 borders; at the 18/19 and anterior border of 21 the relative periphery of the visual field was found. In areas 18 and 19, elevations are represented in a smooth medio-lateral progression from lower to upper visual field. In several cases the elevations in area 21 evidenced a similar medio-lateral progression; however, in others the elevations exhibited a split representation of the horizontal meridian. Anatomically determined callosal connections coincided with the representation of azimuths near the zero meridian. Medio-lateral bands of callosal connectivity that straddle the 17/18 and 19/21 borders are connected by bridges of callosally projecting cells. Acallosal cortical islands corresponded to the peripheral visual field and were found straddling the 18/19 border and the anterior border of area 21. The results are discussed in relation to callosal connectivity and retinotopy in extrastriate visual cortex and to proposed homologies of carnivore and primate visual cortex.}, Author = {Manger, Paul R. and Kiper, Daniel and Masiello, Italo and Murillo, Luis and Tettoni, Laurent and Hunyadi, Zsolt and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Visual Cortex;Retina;Microelectrodes;Image Processing, Computer-Assisted;Female;Not relevant;Ferrets;Electron Transport Complex IV;11 Glia;Brain Mapping;Electrophysiology;Histocytochemistry;Support, Non-U.S. Gov't;Visual Pathways;Visual Fields;Animals;Corpus Callosum}, Medline = {21881437}, Month = {4}, Nlm_Id = {9110718}, Number = {4}, Organization = {Department of Neuroscience, Division of Neuroanatomy and Brain Development, Karolinska Institutet, Retzius v{\"a}g 8, S-171 77 Stockholm, Sweden.}, Pages = {423-37}, Pubmed = {11884357}, Title = {The representation of the visual field in three extrastriate areas of the ferret (Mustela putorius) and the relationship of retinotopy and field boundaries to callosal connectivity}, Uuid = {9C59A774-DA00-4B91-A3AF-5530151EBD30}, Volume = {12}, Year = {2002}} @article{Manger:2002a, Abstract = {On grounds of electrophysiological mapping, cytoarchitecture, myeloarchitecture and callosal and thalamic connectivity, we have identified two cortical areas in the posterior parietal cortex of the ferret: posterior parietal caudal and rostral (PPc and PPr). These areas occupy the lateral and suprasylvian gyri, from the cingulate sulcus (medially) to the suprasylvian sulcus (laterally) and lie between visual areas 18 and 21 (posteriorly) and the somatosensory areas (anteriorly). Within both areas a coarse representation of the visual field was found and within PPr there was also a representation of the body. Each representation mirrors those within neighboring areas. Cytoarchitectonic and myeloarchitectonic fields within this cortical region did not correspond in any simple way to the physiological representations. The architectonic differences correlate to differential callosal connectivity, with predominant connectivity corresponding to the upper hemifield/head representations. PPr and PPc receive thalamic projections from a different, but overlapping, complement of thalamic nuclei. The superimposition of somatic and visual maps in PPr might relate to the probable role of this area in transforming retinal-centered to body-centered spatial coordinates. The organization of the parietal areas in the ferret resembles that of the flying fox and might unveil a common organizational plan from which the primate posterior parietal cortex evolved.}, Author = {Manger, Paul R. and Masiello, Italo and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Histological Techniques;Evoked Potentials, Somatosensory;Dyes;Female;Neural Pathways;Not relevant;Ferrets;11 Glia;Brain Mapping;Electrophysiology;Parietal Lobe;Support, Non-U.S. Gov't;Thalamus;Animals;Corpus Callosum}, Medline = {22314832}, Month = {12}, Nlm_Id = {9110718}, Number = {12}, Organization = {Department of Neuroscience, B2:2, Division of Neuroanatomy and Brain Development, Karolinska Institutet, Retzius v{\"a}g 3, S-171 77 Stockholm, Sweden.}, Pages = {1280-97}, Pubmed = {12427679}, Title = {Areal organization of the posterior parietal cortex of the ferret (Mustela putorius)}, Uuid = {BCC4B8FD-87F7-4A30-919B-BEF877DE6EAA}, Volume = {12}, Year = {2002}} @article{Manger:2004, Abstract = {Using systematic electrophysiological mapping, architectonics and the global pattern of interhemispheric connectivity, we have identified three visual areas in the lateral most part of the posterior suprasylvian gyrus. The most posterior and largest area we call area 20a and anterior to this we defined a smaller area, area 20b. These areas lie lateral to the visual areas 18, 19 and 21 and posterior to a third, but incompletely defined, visual area, area PS. Areas 20a and 20b, emphasize the representation of the upper hemifield. Their interhemispheric connections conform to the so called 'midline rule' in that they are abundant in regions representing central portions of the visual field, scarce or absent elsewhere. These areas are probably homologous to the homonymous areas of the cat and might be indicative of a Bauplan from which the temporal areas of primates may have evolved.}, Author = {Manger, Paul R. and Nakamura, Hiroyuki and Valentiniene, Sonata and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Visual Cortex;Retina;Neurons;Visual Perception;Female;Evoked Potentials, Visual;Ferrets;Not relevant;11 Glia;Brain Mapping;Temporal Lobe;Visual Fields;Animals;Support, Non-U.S. Gov't;Visual Pathways}, Month = {6}, Nlm_Id = {9110718}, Number = {6}, Organization = {Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.}, Pages = {676-89}, Pii = {bhh028}, Pubmed = {15054048}, Title = {Visual areas in the lateral temporal cortex of the ferret (Mustela putorius)}, Uuid = {6488A416-BE7B-4603-AFC5-06755166FABA}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh028}} @article{Mantini:2007, Abstract = {Functional neuroimaging and electrophysiological studies have documented a dynamic baseline of intrinsic (not stimulus- or task-evoked) brain activity during resting wakefulness. This baseline is characterized by slow (<0.1 Hz) fluctuations of functional imaging signals that are topographically organized in discrete brain networks, and by much faster (1-80 Hz) electrical oscillations. To investigate the relationship between hemodynamic and electrical oscillations, we have adopted a completely data-driven approach that combines information from simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Using independent component analysis on the fMRI data, we identified six widely distributed resting state networks. The blood oxygenation level-dependent signal fluctuations associated with each network were correlated with the EEG power variations of delta, theta, alpha, beta, and gamma rhythms. Each functional network was characterized by a specific electrophysiological signature that involved the combination of different brain rhythms. Moreover, the joint EEG/fMRI analysis afforded a finer physiological fractionation of brain networks in the resting human brain. This result supports for the first time in humans the coalescence of several brain rhythms within large-scale brain networks as suggested by biophysical studies.}, Author = {Mantini, D. and Perrucci, M. G. and Del Gratta, C. and Romani, G. L. and Corbetta, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Electroencephalography;research support, non-u.s. gov't;Adult;21 Neurophysiology;Magnetic Resonance Imaging;Oxygen;research support, n.i.h., extramural;Humans;Brain;Male;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {32}, Organization = {Institute of Advanced Biomedical Technologies and Department of Clinical Sciences and Bio-imaging, G. D'Annunzio University Foundation, G. D'Annunzio University, Chieti 66013, Italy. d.mantini\@unich.it}, Pages = {13170-5}, Pii = {0700668104}, Pubmed = {17670949}, Title = {Electrophysiological signatures of resting state networks in the human brain}, Uuid = {FA5DDE54-06F1-435D-88CE-E1990B09538C}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0700668104}} @article{Mao:2001a, Abstract = {Neural progenitor cells are present in the rodent brain throughout adulthood, and can proliferate and differentiate into new neurons and/or glia to repair injury. To explore the repair processes mediated by brain progenitor cells, a selective lesion of the nigrostriatal dopaminergic pathway was induced in young adult mice by repeated administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A thymidine analog, bromodeoxyuridine (BrdU), was used as a tracer for DNA synthesis to label the dividing cells and their terminal progeny following injury. Three days after MPTP treatments (25 mg/kg, once daily for 5 days), an 8-fold increase in the number of BrdU-labeled newborn cells was observed in the dorsal striatum. A 5-fold increase was also seen in the substantia nigra (SN). Newborn cells in the striatum survived beyond 60 days after their birth whereas newborn cells in the SN survived for less than 31 days. The vast majority of newborn cells in the striatum differentiated into astroglia according to their radial morphology and co-expression with an astroglial marker, S100beta, within 10 days after birth. In contrast, most BrdU-positive cells in the SN failed to co-express S100beta. Little or none of BrdU-labeled cells in both the striatum and SN were found to co-localize with a neuronal marker, neuronal nuclear antigen, or tyrosine hydroxylase during the full course of survival days surveyed (3 to 60 days). Repeated MPTP also decreased dopamine content and uptake in the striatum, which showed a significant recovery 31 days after MPTP lesion. These results demonstrate a rapid and profound astrogenesis in the striatum of young adult mice in response to toxic dopaminergic insult. The lack of neurogenesis in the two affected brain areas indicates the relative importance of glial cell regeneration in repairing MPTP injury.}, Author = {Mao, L. and Lau, Y. S. and Petroske, E. and Wang, J. Q.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Cell Survival;Cell Differentiation;MPTP Poisoning;Astrocytes;Dopamine;Animals;Dopamine Agents;3,4-Dihydroxyphenylacetic Acid;Substantia Nigra;Mice, Inbred C57BL;1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine;Male;Research Support, U.S. Gov't, P.H.S.;Neostriatum;Tyrosine 3-Monooxygenase;Age Factors;Mice;Cell Division;24 Pubmed search results 2008;Bromodeoxyuridine;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {21575786}, Month = {11}, Nlm_Id = {8908639}, Number = {1-2}, Organization = {Division of Pharmacology, School of Pharmacy, University of Missouri-Kansas City, 2411 Holmes Street, M3-225, Kansas City, MO, USA}, Pages = {57-65}, Pii = {S0165380601002607}, Pubmed = {11718836}, Title = {Profound astrogenesis in the striatum of adult mice following nigrostriatal dopaminergic lesion by repeated MPTP administration}, Uuid = {EA4AC4AC-945B-44F0-8380-71CB1C396E6D}, Volume = {131}, Year = {2001}} @article{Mao:2001, Abstract = {The flow of activity in the cortical microcircuitry is poorly understood. We use calcium imaging to reconstruct, with millisecond and single-cell resolution, the spontaneous activity of populations of neurons in unstimulated slices from mouse visual cortex. We find spontaneous activity correlated among networks of layer 5 pyramidal cells. Synchronous ensembles occupy overlapping territories, often share neurons, and are repeatedly activated. Sets of neurons are also sequentially activated numerous times. Network synchronization and sequential correlations are blocked by glutamatergic antagonists, even though spontaneous firing persists in many "autonomously active" neurons. This autonomous activity is periodic and depends on hyperpolarization-activated cationic (H) and persistent sodium (Na(p)) currents. We conclude that the isolated neocortical microcircuit generates spontaneous activity, mediated by a combination of intrinsic and circuit mechanisms, and that this activity can be temporally precise.}, Author = {Mao, B. Q. and Hamzei-Sichani, F. and Aronov, D. and Froemke, R. C. and Yuste, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Neurons;Visual Cortex;21 Neurophysiology;Action Potentials;Pyramidal Cells;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred C57BL;21 Calcium imaging;Neocortex;In Vitro;Mice;Animals;24 Pubmed search results 2008;Membrane Potentials;Excitatory Amino Acid Antagonists}, Medline = {21603134}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {883-98}, Pii = {S0896-6273(01)00518-9}, Pubmed = {11738033}, Title = {Dynamics of spontaneous activity in neocortical slices}, Uuid = {2E3F25D4-E90F-4FDD-A5A0-B6A58B4942AE}, Volume = {32}, Year = {2001}, url = {papers/Mao_Neuron2001.pdf}} @article{Mao:1999, Abstract = {During mammalian development, electrical activity promotes the calcium-dependent survival of neurons that have made appropriate synaptic connections. However, the mechanisms by which calcium mediates neuronal survival during development are not well characterized. A transcription-dependent mechanism was identified by which calcium influx into neurons promoted cell survival. The transcription factor MEF2 was selectively expressed in newly generated postmitotic neurons and was required for the survival of these neurons. Calcium influx into cerebellar granule neurons led to activation of p38 mitogen-activated protein kinase-dependent phosphorylation and activation of MEF2. Once activated, MEF2 regulated neuronal survival by stimulating MEF2-dependent gene transcription. These findings demonstrate that MEF2 is a calcium-regulated transcription factor and define a function for MEF2 during nervous system development that is distinct from previously well-characterized functions of MEF2 during muscle differentiation.}, Author = {Mao, Z. and Bonni, A. and Xia, F. and Nadal-Vicens, M. and Greenberg, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Cell Survival;Cell Differentiation;Signal Transduction;p38 Mitogen-Activated Protein Kinases;DNA-Binding Proteins;Animals;Rats;Transfection;Cells, Cultured;Mitosis;Phosphorylation;Apoptosis;Transcription Factors;Mutation;Calcium;research support, non-u.s. gov't;Myogenic Regulatory Factors;Dimerization;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Cerebral Cortex;Neurons;Cerebellum;24 Pubmed search results 2008;Calcium Channels, L-Type;Immunohistochemistry;Mitogen-Activated Protein Kinases;Transcription, Genetic}, Month = {10}, Nlm_Id = {0404511}, Number = {5440}, Organization = {Division of Neuroscience, Department of Neurology, Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {785-90}, Pii = {7931}, Pubmed = {10531066}, Title = {Neuronal activity-dependent cell survival mediated by transcription factor MEF2}, Uuid = {F543137E-7CB7-4D13-9AAB-10FC4B6F1E26}, Volume = {286}, Year = {1999}} @article{Marandi:2007, Author = {Marandi, Nima and Konnerth, Arthur}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {23 Technique;24 Pubmed search results 2008;Image Processing, Computer-Assisted;Lasers;Time Factors;Cerebrovascular Circulation;Brain Mapping;comment;Microscopy, Fluorescence;Nerve Net;Sensitivity and Specificity;Cerebral Cortex;Brain Chemistry;news}, Month = {1}, Nlm_Id = {101215604}, Number = {1}, Pages = {19-20}, Pii = {nmeth0107-19}, Pubmed = {17195020}, Title = {4D brain signaling}, Uuid = {3F23C331-CF57-4CCC-A18E-3B5ABF46CC50}, Volume = {4}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth0107-19}} @article{Marandi:2002, Abstract = {Two-photon laser scanning microscopy has been used successfully for imaging activity-dependent changes of intracellular calcium and sodium levels. Here we introduce a simple technique for two-photon chloride imaging in intact neurons. It involves the use of the membrane-permeable Cl(-) indicator dye MQAE [N-(6-methoxyquinolyl) acetoethyl ester]. Brief incubation with MQAE produced a robust loading of cells in slices from various brain regions including hippocampus, cortex and cerebellum. In contrast to conventional fluorescence measurements using MQAE, two-photon imaging was not affected in a major way by dye bleaching and phototoxic damage. Instead, it allowed prolonged recordings of time-resolved changes in intracellular chloride concentration in somata and dendrites. As an example of an application we imaged GABA-mediated Cl(-) transients in pyramidal cells of cortical and hippocampal slices as well as in cerebellar Purkinje neurons. By combining Cl(-) imaging with the gramicidin-based perforated-patch-clamp technique we showed that changes in MQAE fluorescence are proportional to the magnitudes of GABA-evoked transmembrane Cl(-) fluxes. Thus, MQAE-based two-photon microscopy promises to be a valuable technique for many applications requiring chloride imaging in single cells.}, Author = {Marandi, Nima and Konnerth, Arthur and Garaschuk, Olga}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0031-6768}, Journal = {Pflugers Arch}, Keywords = {Fluorescent Dyes;Animals;In Vitro;Rats;Microscopy, Confocal;Chlorides;Brain;Rats, Sprague-Dawley;in vitro ;Quinolines;research support, non-u.s. gov't ;Models, Chemical;21 Neurophysiology;Neurons;Photons;24 Pubmed search results 2008;Intracellular Membranes;Research Support, Non-U.S. Gov't}, Medline = {22354843}, Month = {12}, Nlm_Id = {0154720}, Number = {3}, Organization = {Institut f{\"u}r Physiologie, Ludwig-Maximilians Universit{\"a}t M{\"u}nchen, Pettenkoferstrasse 12, 80336 Munich, Germany.}, Pages = {357-65}, Pubmed = {12466938}, Title = {Two-photon chloride imaging in neurons of brain slices}, Uuid = {9147438E-40AF-4286-853E-580D7D512E5B}, Volume = {445}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00424-002-0933-7}} @article{Marder:2005, Abstract = {The networks that generate rhythmic motor patterns in invertebrates and vertebrates are ideal for studying the mechanisms by which functional circuits are formed during development. Rhythmic motor patterns and movements are seen embryonically, before they are needed for behavior; recent work suggests that activity in immature spinal cord networks is important for circuit formation and transmitter specification. Despite significant advances in describing the patterns of transcription factor expression in both invertebrate nervous systems and vertebrate spinal cord, a real understanding of how central pattern generators develop is hindered by our lack of knowledge of the organization of these circuits in adults.}, Author = {Marder, Eve and Rehm, Kristina J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 02:59:44 +0000}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Motor Activity;Nerve Net;Animals;Humans;24 Pubmed search results 2008;review; currOpinRvw}, Month = {2}, Nlm_Id = {9111376}, Number = {1}, Organization = {Volen Center, Biology Department, Brandeis University, Waltham, Massachusetts 02454-9110, USA. marder\@brandeis.edu}, Pages = {86-93}, Pii = {S0959-4388(05)00012-7}, Pubmed = {15721749}, Title = {Development of central pattern generating circuits}, Uuid = {C45E0699-837D-447F-B00A-D882061A61F5}, Volume = {15}, Year = {2005}, url = {papers/Marder_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.01.011}} @article{Marder:2002, Abstract = {Early neuroscientists scoured the animal kingdom for the ideal preparation with which to study specific problems of interest. Today, non-mammalian nervous systems continue to provide ideal platforms for the study of fundamental problems in neuroscience. Indeed, the peculiarities of body plan and nervous systems that have evolved to carry out precise tasks in unique ecological niches enable investigators not only to pose specific scientific questions, but also to uncover principles that are general to all nervous systems. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Marder, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:53 -0400}, Journal = {Nature}, Keywords = {10 Development;Neurosciences/methods;*Models, Animal;Behavior, Animal/physiology;Nervous System/cytology/*embryology;*Nervous System Physiology;Animals;F pdf;Learning/physiology}, Number = {6886}, Organization = {Volen Center, Brandeis University, Waltham, MA 02454-9110, USA. marder\@brandeis.edu}, Pages = {318-21}, Title = {Non-mammalian models for studying neural development and function}, Uuid = {D0EBE8BF-DA3D-42FC-9DE3-2570DEDAF684}, Volume = {417}, Year = {2002}, url = {papers/Marder_Nature2002.pdf}} @article{Margolis:1972, Author = {Margolis, F. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Hamsters;Rabbits;Immune Sera;13 Olfactory bulb anatomy;I;Rats;Goats;Female;Animal;Species Specificity;Male;Immunoelectrophoresis;Brain Chemistry;Ammonium Sulfate;Immunodiffusion;Organ Specificity;Limbic System/*analysis;Olfactory Bulb/analysis;Chromatography, DEAE-Cellulose;Mice;Electrophoresis, Disc;Molecular Weight;Guinea Pigs;Precipitin Tests;Chickens;Nerve Tissue Proteins/*isolation &purification}, Number = {5}, Pages = {1221-4.}, Title = {A brain protein unique to the olfactory bulb}, Uuid = {435F6C0D-02F6-4355-9D62-0E7B58217F9A}, Volume = {69}, Year = {1972}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=4624756}} @article{Marin-Burgin:2006, Abstract = {During development, many embryos show electrical coupling among neurons that is spatially and temporally regulated. For example, in vertebrate embryos extensive dye coupling is seen during the period of circuit formation, suggesting that electrical connections could pre-figure circuits, but it has been difficult to identify which neuronal types are coupled. We have used the leech Hirudo medicinalis to follow the development of electrical connections within the circuit that produces local bending. This circuit consists of three layers of neurons: four mechanosensory neurons (P cells), 17 identified interneurons, and approximately 24 excitatory and inhibitory motor neurons. These neurons can be identified in embryos, and we followed the spatial and temporal dynamics as specific connections developed. Injecting Neurobiotin into identified cells of the circuit revealed that electrical connections were established within this circuit in a precise manner from the beginning. Connections first appeared between motor neurons; mechanosensory neurons and interneurons started to connect at least a day later. This timing correlates with the development of behaviors, so the pattern of emerging connectivity could explain the appearance first of spontaneous behaviors (driven by a electrically coupled motor network) and then of evoked behaviors (when sensory neurons and interneurons are added to the circuit).}, Author = {Marin-Burgin, Antonia and Eisenhart, F. James and Kristan, William B. and French, Kathleen A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0340-7594}, Journal = {J Comp Physiol A Neuroethol Sens Neural Behav Physiol}, Keywords = {Behavior, Animal;21 Neurophysiology;Movement;Central Nervous System;Neuronal Plasticity;Research Support, N.I.H., Extramural;Leeches;Animals;24 Pubmed search results 2008;Neurons}, Month = {2}, Nlm_Id = {101141792}, Number = {2}, Organization = {Section of Neurobiology, Division of Biological Sciences, University of California, 3119 Pacific Hall, San Diego, La Jolla, CA 92093-0357, USA. aburgin\@ucsd.edu}, Pages = {123-33}, Pubmed = {16205960}, Title = {Embryonic electrical connections appear to pre-figure a behavioral circuit in the leech CNS}, Uuid = {5B68DA4B-CBCC-4D65-86DB-CE82F9CAAB15}, Volume = {192}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00359-005-0055-8}} @article{Marin-Padilla:1995, Abstract = {The prenatal developmental histories of layer I, fibrous (white matter), and protoplasmic (gray matter) astrocytes have been studied in the human neocortex by the rapid Golgi method. The developmental route followed by each of these astrocytes is a distinct process which evolves from a specific precursor, occurs at a different time, and is linked to a specific event. The differentiation of layer I astrocytes is linked to the neocortex external glial limiting membrane (EGLM), that of fibrous astrocytes to the early white matter vascularization and maturation, and that of protoplasmic astrocytes to the late gray matter ascending vascularization and maturation. At the start of development, three glial precursors are established in the neocortex: 1) original radial neuroectodermal cells with nuclei above the primordial plexiform layer (PPL) by losing their ependymal and retaining their pial attachments become early astrocytes of layer I and EGLM components; 2) neuroectodermal cells with nuclei below the PPL that retain their pial and ependymal attachments become type I radial glial cells which are committed to the guidance of neurons and the early EGLM maintenance; and, 3) neuroectodermal cells that lose their pial but retain their ependymal attachment are transformed into type II radial glial precursors. By progressively losing their ependymal attachment, type II radial glia precursors become freely migrating cells, establish vascular contacts, and differentiate into fibrous astrocytes (and into oligodendrocytes?) throughout the subplate, developing white matter, and paraventricular regions. After the formation of the gray matter, additional layer I astrocytes are needed for the EGLM late prenatal and postnatal maintenance because type I radial glia cells start to regress and to reabsorb their EGLM endfeet. A late ependyma-to-pia migration of glial precursors progressively repopulates layer I with additional astrocytes and establishes the ephemeral subpial granular layer (SGL) of Ranke. From the 15th week of gestation to the time of birth, late astrocytes of layer I lose their EGLM attachments, migrate freely into the maturing gray matter, establish vascular contacts, and differentiate into protoplasmic astrocytes. The protoplasmic astrocytes of the gray matter evolve from transformation of layer I astrocytes rather than from radial glia cells as is generally believed.}, Author = {Marin-Padilla, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {G;Human;Cell Differentiation;10 Development;Astrocytes;Humans;Cell Movement;Staining and Labeling;11 Glia;Astrocytes/*chemistry;Embryonic and Fetal Development;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Cell Differentiation/physiology;24 Pubmed search results 2008;Fetal Development/physiology;Cerebral Cortex/*anatomy &histology/chemistry/embryology}, Medline = {95403735}, Month = {7}, Nlm_Id = {0406041}, Number = {4}, Organization = {Department of Pathology, Dartmouth Medical School, Hanover, New Hampshire 03755, USA.}, Pages = {554-72.}, Pubmed = {7545703}, Title = {Prenatal development of fibrous (white matter), protoplasmic (gray matter), and layer I astrocytes in the human cerebral cortex: a Golgi study}, Uuid = {E3FDA3AC-C3A4-44E0-9FAF-D947C974A82F}, Volume = {357}, Year = {1995}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903570407}, Bdsk-Url-2 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7545703}} @article{Marino:2005, Abstract = {Cortical computations critically involve local neuronal circuits. The computations are often invariant across a cortical area yet are carried out by networks that can vary widely within an area according to its functional architecture. Here we demonstrate a mechanism by which orientation selectivity is computed invariantly in cat primary visual cortex across an orientation preference map that provides a wide diversity of local circuits. Visually evoked excitatory and inhibitory synaptic conductances are balanced exquisitely in cortical neurons and thus keep the spike response sharply tuned at all map locations. This functional balance derives from spatially isotropic local connectivity of both excitatory and inhibitory cells. Modeling results demonstrate that such covariation is a signature of recurrent rather than purely feed-forward processing and that the observed isotropic local circuit is sufficient to generate invariant spike tuning.}, Author = {Mari\~{n}o, Jorge and Schummers, James and Lyon, David C. and Schwabe, Lars and Beck, Oliver and Wiesing, Peter and Obermayer, Klaus and Sur, Mriganka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {gamma-Aminobutyric Acid;Cholera Toxin;Visual Cortex;Animals;Photic Stimulation;Synapses;comparative study;Visual Perception;research support, u.s. gov't, p.h.s. ;Diagnostic Imaging;Synaptic Transmission;Cell Count;Patch-Clamp Techniques;comparative study ;research support, non-u.s. gov't;Orientation;research support, non-u.s. gov't ;Computer Simulation;Nerve Net;Action Potentials;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Immunohistochemistry;Neural Inhibition;Models, Neurological;Cats;Brain Mapping}, Month = {2}, Nlm_Id = {9809671}, Number = {2}, Organization = {Department of Brain and Cognitive Sciences and Picower Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.}, Pages = {194-201}, Pii = {nn1391}, Pubmed = {15665876}, Title = {Invariant computations in local cortical networks with balanced excitation and inhibition}, Uuid = {B0F8A70C-219E-4F74-8FDE-D3723E1B3971}, Volume = {8}, Year = {2005}, url = {papers/Marino_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1391}} @article{Marin:2006, Abstract = {The special conformation of the developing nervous system, in which progenitor zones are largely confined to the lumen of the neural tube, places neuronal migration as one of the most fundamental processes in brain development. Previous studies have shown that different neuronal types adopt distinct morphological modes of migration in the developing brain, indicating that neuronal migration might be a diverse process. Here, we review recent data on the molecular mechanisms underlying neuronal migration that suggest that similar signaling principles are responsible for the frequently variable morphology of different types of migrating neuron. According to this idea, the same basic molecular mechanisms found in other cell types, such as fibroblasts, might have been adapted to the special morphological needs of migrating neurons in different regions of the developing brain.}, Author = {Mar{\'\i}n, Oscar and Valdeolmillos, Miguel and Moya, Fernando}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {7808616}, Number = {12}, Organization = {Instituto de Neurociencias de Alicante, CSIC and Universidad Miguel Hern{\'a}ndez, 03550 Sant Joan d'Alacant, Spain. o.marin\@umh.es}, Pages = {655-61}, Pii = {S0166-2236(06)00223-2}, Pubmed = {17046074}, Title = {Neurons in motion: same principles for different shapes?}, Uuid = {09473F7F-E1D2-4F76-AACB-A44AEC5C9C92}, Volume = {29}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.10.001}} @article{Marin-Teva:2004, Abstract = {The loss of neuronal cells, a prominent event in the development of the nervous system, involves regulated triggering of programmed cell death, followed by efficient removal of cell corpses. Professional phagocytes, such as microglia, contribute to the elimination of dead cells. Here we provide evidence that, in addition to their phagocytic activity, microglia promote the death of developing neurons engaged in synaptogenesis. In the developing mouse cerebellum, Purkinje cells die, and 60\%of these neurons that already expressed activated caspase-3 were engulfed or contacted by spreading processes emitted by microglial cells. Apoptosis of Purkinje cells in cerebellar slices was strongly reduced by selective elimination of microglia. Superoxide ions produced by microglial respiratory bursts played a major role in this Purkinje cell death. Our study illustrates a mammalian form of engulfment-promoted cell death that links the execution of neuron death to the scavenging of dead cells.}, Author = {Mar{\'\i}n-Teva, Jos{\'e} Luis and Dusart, Isabelle and Colin, Catherine and Gervais, Annie and van Rooijen, Nico and Mallat, Michel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Apoptosis/*physiology;Purkinje Cells/cytology/*physiology;Cell Communication/*physiology;Cell Differentiation;Apoptosis;Cell Survival;Caspases/metabolism;Alpha;Signal Transduction/*physiology;Animals;Presynaptic Terminals/physiology;Antibodies/pharmacology;Presynaptic Terminals;Cerebellar Cortex;In Vitro;Signal Transduction;Caspases;Free Radical Scavengers/pharmacology;Cell Respiration/drug effects/physiology;Purkinje Cells;Mice, Inbred C57BL;Cell Differentiation/physiology;Receptors, Tumor Necrosis Factor/antagonists &inhibitors/metabolism;Cell Communication;Not relevant;Cell Survival/drug effects/physiology;Enzyme Inhibitors;Receptors, Tumor Necrosis Factor;Cerebellar Cortex/cytology/*growth &development;Enzyme Inhibitors/pharmacology;Cell Respiration;EE, G pdf;Microglia;Mice, Knockout;Mice;Antibodies;Microglia/cytology/*physiology;Support, Non-U.S. Gov't;Free Radical Scavengers}, Month = {2}, Nlm_Id = {8809320}, Number = {4}, Organization = {Biologie des Interactions Neurone-glie, INSERM U.495, IFR 70, UPMC, 47 Bd de l'h\^{o}pital, 75013 Paris, France.}, Pages = {535-47}, Pii = {S0896627304000698}, Pubmed = {14980203}, Title = {Microglia promote the death of developing Purkinje cells}, Uuid = {79AF5F34-D3BA-11D9-A0E9-000D9346EC2A}, Volume = {41}, Year = {2004}} @article{Markakis:1999, Abstract = {The subgranule zone of the dentate gyrus in rats has been shown to be proliferative into adulthood and senescence. However, the connectivity of newly generated, identified neurons in the adult has not been definitively described. In the present study, 9 weeks after a series of intraperitoneal injections of 5-bromo-2'-deoxyuridine (BrdU), animals received stereotaxic iontophoretic injections of Fluoro-Gold (FG) into field CA3. Three weeks after FG injections, sections were analyzed for BrdU immunoreactivity (proliferative label), FG retrograde label, and either calbindin-D28k or synaptophysin immunohistochemistry. A large proportion (up to 44\%) of BrdU-labeled cells in the dentate gyrus within regions of FG retrograde label incorporated FG. All of the doubly labeled (BrdU-FG) neurons also immunolabeled with the antibody to calbindin-D28k. Many doubly labeled (BrdU-FG) cells were also surrounded in three planes by synaptophysin immunoreactivity. We conclude that newly generated neurons in the dentate gyrus have the correct immunohistochemical profile, send appropriate axonal projections to field CA3, and are surrounded by profiles containing synaptic vesicle proteins.}, Author = {Markakis, E. A. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Comp Neurol}, Keywords = {Fluorescent Dyes;Neural Pathways/chemistry/ultrastructure;Synaptic Vesicles/*chemistry/ultrastructure;Rats;Iontophoresis;Dentate Gyrus/*chemistry/cytology;Animal;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Nerve Tissue Proteins/analysis;Axons/*chemistry/ultrastructure;Synaptophysin/analysis;Male;Calcium-Binding Protein, Vitamin D-Dependent/analysis;B;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Bromodeoxyuridine;Neurons/*chemistry/ultrastructure}, Number = {4}, Organization = {The Salk Institute for Biological Studies, Laboratory of Genetics, La Jolla, California 92037, USA.}, Pages = {449-60.}, Title = {Adult-generated neurons in the dentate gyrus send axonal projections to field CA3 and are surrounded by synaptic vesicles}, Uuid = {22E070E4-C6EA-4209-B831-D929468E4ED0}, Volume = {406}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10205022}} @article{Markakis:2004, Abstract = {We report the first isolation of progenitor cells from the hypothalamus, a derivative of the embryonic basal plate that does not exhibit neurogenesis postnatally. Neurons derived from hypothalamic progenitor cells were compared with those derived from progenitor cultures of hippocampus, an embryonic alar plate derivative that continues to support neurogenesis in vivo into adulthood. Aside from their different embryonic origins and their different neurogenic potential in vivo, these brain regions were chosen because they are populated with cells of three different categories: Category I cells are generated in both hippocampus and hypothalamus, Category II cells are generated in the hypothalamus but are absent from the hippocampus, and Category III is a cell type generated in the olfactory placode that migrates into the hypothalamus during development. Stem-like cells isolated from other brain regions, with the ability to generate neurons and glia, produce neurons of several phenotypes including gabaergic, dopaminergic, and cholinergic lineages. In the present study, we extended our observations into neuroendocrine phenotypes. The cultured neural precursors from 7-week-old rat hypothalamus readily generated neuropeptide-expressing neurons. Hippocampal and hypothalamic progenitor cultures converged to indistinguishable populations and produced neurons of all three categories, confirming that even short-term culture confers or selects for immature progenitors with enough plasticity to elaborate neuronal phenotypes usually inhibited in vivo by the local microenvironment. The range of phenotypes generated from neuronal precursors in vitro now includes the peptides found in the neuroendocrine system: corticotropin-releasing hormone, growth hormone-releasing hormone, gonadotropin-releasing hormone, oxytocin, somatostatin, thyrotropin-releasing hormone, and vasopressin.}, Author = {Markakis, Eleni A. and Palmer, Theo D. and Randolph-Moore, Lynne and Rakic, Pasko and Gage, Fred H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Animals;Cell Separation;Cells, Cultured;Rats;Neurosecretory Systems;Comparative Study;Phenotype;Antigens, Differentiation;Cell Count;Rats, Sprague-Dawley;Hippocampus;RNA, Messenger;Corticotropin-Releasing Hormone;Male;Reverse Transcriptase Polymerase Chain Reaction;Neuropeptides;Rats, Inbred F344;Hypothalamus;Support, Non-U.S. Gov't;Neurons;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Stem Cells}, Month = {3}, Nlm_Id = {8102140}, Number = {12}, Organization = {Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Pages = {2886-97}, Pii = {24/12/2886}, Pubmed = {15044527}, Title = {Novel neuronal phenotypes from neural progenitor cells}, Uuid = {B9D50436-CB07-4FA2-86B8-0184D7B67599}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4161-03.2004}} @article{Markram:1997, Abstract = {Tufted layer 5 (TL5) pyramidal neurons are important projection neurons from the cerebral cortex to subcortical areas. Recent and ongoing experiments aimed at understanding the computational analysis performed by a network of synaptically connected TL5 neurons are reviewed here. The experiments employed dual and triple whole-cell patch clamp recordings from visually identified and preselected neurons in brain slices of somatosensory cortex of young (14- to 16-day-old) rats. These studies suggest that a local network of TL5 neurons within a cortical module of diameter 300 microns consists of a few hundred neurons that are extensively inter-connected with reciprocal feedback from at least first-, second- and third-order target neurons. A statistical analysis of synaptic innervation suggests that this recurrent network is not randomly arranged and hence each neuron could be functionally unique. Synaptic transmission between these neurons is characterized by use-dependent synaptic depression which confers novel properties to this recurrent network of neurons. First, a range of rates of depression for different synaptic connections enable each TL5 neuron to receive a unique mixture of information about the average firing rates and the temporally correlated action potential (AP) activity in the population of presynaptic TL5 neurons. Second, each AP generated by any neuron in the network induces a change (defined as an iteration step) in the functional coupling of the neurons in the network (defined as network configuration). It is proposed that the network configuration is iterated during a stimulus to achieve an optimally orchestrated network response. Hebbian, anti-Hebbian and neuromodulatory-induced modifications of neurotransmitter release probability change the rates of synaptic depression and thereby alter the iteration step size. These data may be important to understand the dynamics of electrical activity within the network.}, Author = {Markram, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Pyramidal Cells;Research Support, U.S. Gov't, Non-P.H.S.;Synaptic Transmission;Nerve Net;Animals;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Medline = {97422090}, Month = {9}, Nlm_Id = {9110718}, Number = {6}, Organization = {Department of Neurobiology, Weizmann Institute for Science, Rehovot, Israel. bnmark\@weizmann.weizmann.ac.il}, Pages = {523-33}, Pubmed = {9276177}, Title = {A network of tufted layer 5 pyramidal neurons}, Uuid = {5B296C16-49C9-44DC-A187-39F620B74594}, Volume = {7}, Year = {1997}} @article{Markram:1995, Abstract = {1. Dendrites of rat neocortical layer V pyramidal neurons were loaded with the Ca2+ indicator dye Calcium Green-1 (CG-1) or fluo-3, and the mechanisms which govern action potential (AP)-evoked transient changes in dendritic cytosolic Ca2+ concentration ([Ca2+]i) were examined. APs were initiated either by synaptic stimulation or by depolarizing the soma or dendrite by current injection, and changes in fluorescence of the indicator dye were measured in the proximal 170 microns of the apical dendrite. 2. Simultaneous two-pipette recordings of APs from the soma and apical dendrite, and dendritic fluorescence imaging indicated that a single AP propagating from the soma into the apical dendrite evokes a rapid transient increase in fluorescence indicating a transient increase in [Ca2+]i. At 35-37 degrees C the decay time constant of the fluorescence transient following an AP was around 80 ms. 3. Voltage-activated Ca2+ channels (VACCs) of several subtypes mediated the AP-evoked fluorescence transient in the proximal (100-170 microns) apical dendrite. The AP-evoked fluorescence transient resulted from Ca2+ entry through L-type (nifedipine sensitive; 25\%), N-type (omega-conotoxin GVIA sensitive; 28\%) and P-type (omega-agatoxin IVA sensitive; 10\%) Ca2+ channels and through Ca2+ channels (R-type) not sensitive to L-, N- and P-type Ca2+ channel blockers (cadmium ion sensitive; 37\%). 4. The decay time course of the dendritic fluorescence transient was prolonged by the blockers of endoplasmic reticulum (ER) Ca(2+)-ATPase, cyclopiazonic acid and thapsigargin, suggesting that uptake of Ca2+ into the ER in dendrites governs clearance of dendritic Ca2+. 5. The decay time course of the fluorescence transient was slightly prolonged by benzamil, a blocker of plasma membrane Na(+)-Ca2+ exchange and by calmidazolium, a blocker of the calmodulin-dependent plasma membrane Ca(2+)-ATPase, suggesting that these pathways are less important for dendrite Ca2+ clearance following a single AP. Neither the mitochondrial uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) nor the blocker of Ca2+ uptake into mitochondria, Ruthenium Red, had any measurable effect on the decay time course of the fluorescence transient. 6. Dendritic fluorescence transients measured during trains of dendritic APs began to summate at impulse frequencies of 5 APs s-1. At higher frequencies APs caused a concerted and maintained elevation of dendritic fluorescence during the train.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Markram, H. and Helm, P. J. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Fluorescence;Electrophysiology;Animals;In Vitro;Rats;Tetraethylammonium Compounds;Spectrometry, Fluorescence;Mitochondria;Cell Membrane;Ca(2+)-Transporting ATPase;Pyramidal Cells;Rats, Wistar;Calcium;Microscopy, Fluorescence;Endoplasmic Reticulum;Dendrites;Action Potentials;Cerebral Cortex;21 Neurophysiology;Potassium Channels;Sodium;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {95387286}, Month = {5}, Nlm_Id = {0266262}, Organization = {Max-Planck-Institut f{\"u}r medizinische Forschung, Heidelberg, Germany.}, Pages = {1-20}, Pubmed = {7658365}, Title = {Dendritic calcium transients evoked by single back-propagating action potentials in rat neocortical pyramidal neurons}, Uuid = {926FA11B-4B2A-4DEE-962A-C7124965048F}, Volume = {485 ( Pt 1)}, Year = {1995}} @article{Markram:1997a, Abstract = {1. Dual voltage recordings were made from pairs of adjacent, synaptically connected thick tufted layer 5 pyramidal neurones in brain slices of young rat (14-16 days) somatosensory cortex to examine the physiological properties of unitary EPSPs. Pre- and postsynaptic neurones were filled with biocytin and examined in the light and electron microscope to quantify the morphology of axonal and dendritic arbors and the number and location of synaptic contacts on the target neurone. 2. In 138 synaptic connections between pairs of pyramidal neurones 96 (70\%) were unidirectional and 42 (30\%) were bidirectional. The probability of finding a synaptic connection in dual recordings was 0.1. Unitary EPSPs evoked by a single presynaptic action potential (AP) had a mean peak amplitude ranging from 0.15 to 5.5 mV in different connections with a mean of 1.3 +/- 1.1 mV, a latency of 1.7 +/- 0.9 ms, a 20-80\%rise time of 2.9 +/- 2.3 ms and a decay time constant of 40 +/- 18 ms at 32-24 degrees C and -60 +/- 2 mV membrane potential. 3. Peak amplitudes of unitary EPSPs fluctuated randomly from trial to trial. The coefficient of variation (c.v.) of the unitary EPSP amplitudes ranged from 0.13 to 2.8 in different synaptic connections (mean, 0.52; median, 0.41). The percentage of failures of single APs to evoke a unitary EPSP ranged from 0 to 73\%(mean, 14\%; median, 7\%). Both c.v. and percentage of failures decreased with increasing mean EPSP amplitude. 4. Postsynaptic glutamate receptors which mediate unitary EPSPs at -60 mV were predominantly of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor type. Receptors of the N-methyl-D-aspartate (NMDA) type contributed only a small fraction (< 20\%) to the voltage-time integral of the unitary EPSP at -60 mV, but their contribution increased at more positive membrane potentials. 5. Branching patterns of dendrites and axon collaterals of forty-five synaptically connected neurones, when examined in the light microscope, indicated that the axonal and dendritic anatomy of both projecting and target neurones and of uni- and bidirectionally connected neurones was uniform. 6. The number of potential synaptic contacts formed by a presynaptic neurone on a target neurone varied between four and eight (mean, 5.5 +/- 1.1 contacts; n = 19 connections). Synaptic contacts were preferentially located on basal dendrites (63\%, 82 +/- 35 microns from the soma, n = 67) and apical oblique dendrites (27\%, 145 +/- 59 microns, n = 29), and 35\%of all contacts were located on tertiary basal dendritic branches. The mean geometric distances (from the soma) of the contacts of a connection varied between 80 and 585 microns (mean, 147 microns; median, 105 microns). The correlation between EPSP amplitude and the number of morphologically determined synaptic contacts or the mean geometric distances from the soma was only weak (correlation coefficients were 0.2 and 0.26, respectively). 7. Compartmental models constructed from camera lucida drawings of eight target neurones showed that synaptic contacts were located at mean electrotonic distances between 0.07 and 0.33 from the soma (mean, 0.13). Simulations of unitary EPSPs, assuming quantal conductance changes with fast rise time and short duration, indicated that amplitudes of quantal EPSPs at the soma were attenuated, on average, to < 10\%of dendritic EPSPs and varied in amplitude up to 10-fold depending on the dendritic location of synaptic contacts. The inferred quantal peak conductance increase varied between 1.5 and 5.5 nS (mean, 3 nS). 8. The combined physiological and morphological measurements in conjunction with EPSP simulations indicated that the 20-fold range in efficacy of the synaptic connections between thick tufted pyramidal neurones, which have their synaptic contacts preferentially located on basal and apical oblique dendrites, was due to differences in transmitter release probability of the projecting neurones and, to a lesser extent, to differenc}, Author = {Markram, H. and L{\"u}bke, J. and Frotscher, M. and Roth, A. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Microscopy, Interference;Microscopy, Video;Electric Stimulation;Electric Conductivity;Synapses;Animals;Rats;Synaptic Transmission;Patch-Clamp Techniques;Receptors, AMPA;Pyramidal Cells;Rats, Wistar;Time Factors;Dendrites;Action Potentials;Cell Size;21 Neurophysiology;Cerebral Cortex;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Ion Channel Gating;Research Support, Non-U.S. Gov't}, Medline = {97292817}, Month = {4}, Nlm_Id = {0266262}, Organization = {Max-Planck-Institut f{\"u}r Medizinische Forschung, Abteilung Zellphysiologie, Germany. bnmark\@weizmann.weizmann.ac.il}, Pages = {409-40}, Pubmed = {9147328}, Title = {Physiology and anatomy of synaptic connections between thick tufted pyramidal neurones in the developing rat neocortex}, Uuid = {ED19386E-B2B6-4B5B-BE9A-B1A849EDF999}, Volume = {500 ( Pt 2)}, Year = {1997}} @article{Markram:2004, Abstract = {Mammals adapt to a rapidly changing world because of the sophisticated cognitive functions that are supported by the neocortex. The neocortex, which forms almost 80\%of the human brain, seems to have arisen from repeated duplication of a stereotypical microcircuit template with subtle specializations for different brain regions and species. The quest to unravel the blueprint of this template started more than a century ago and has revealed an immensely intricate design. The largest obstacle is the daunting variety of inhibitory interneurons that are found in the circuit. This review focuses on the organizing principles that govern the diversity of inhibitory interneurons and their circuits.}, Author = {Markram, Henry and Toledo-Rodriguez, Maria and Wang, Yun and Gupta, Anirudh and Silberberg, Gilad and Wu, Caizhi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Electrophysiology;Animals;Synapses;Humans;Research Support, U.S. Gov't, Non-P.H.S.;Neocortex;Synaptic Transmission;review;Axons;Ion Channels;Neuropeptides;Dendrites;Nerve Net;Neurons;21 Neurophysiology;Membrane Potentials;Calcium-Binding Proteins;Interneurons;24 Pubmed search results 2008;Neural Inhibition;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {100962781}, Number = {10}, Organization = {Laboratory of Neural Microcircuitry, Brain Mind Institute, Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, 1015 Lausanne, Switzerland. Henry.markram\@epfl.ch}, Pages = {793-807}, Pii = {nrn1519}, Pubmed = {15378039}, Title = {Interneurons of the neocortical inhibitory system}, Uuid = {4F96E7AE-B6E4-492D-839A-51FAE2593FD8}, Volume = {5}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1519}} @article{Markram:2006, Abstract = {IBM's Blue Gene supercomputer allows a quantum leap in the level of detail at which the brain can be modelled. I argue that the time is right to begin assimilating the wealth of data that has been accumulated over the past century and start building biologically accurate models of the brain from first principles to aid our understanding of brain function and dysfunction.}, Author = {Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Neural Networks (Computer);21 Neurophysiology;Models, Neurological;Research Support, U.S. Gov't, Non-P.H.S.;Quantum Theory;Humans;Brain;Animals;review;neuroinformatics}, Month = {2}, Nlm_Id = {100962781}, Number = {2}, Organization = {Laboratory of Neural Microcircuitry, Brain Mind Institute, Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne, Lausanne 1015, Switzerland. henry.markram\@epfl.ch}, Pages = {153-60}, Pii = {nrn1848}, Pubmed = {16429124}, Title = {The blue brain project}, Uuid = {1FD41476-7138-4766-97B8-A503483C774D}, Volume = {7}, Year = {2006}, url = {papers/Markram_NatRevNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1848}} @article{Markram:1996, Abstract = {Experience-dependent potentiation and depression of synaptic strength has been proposed to subserve learning and memory by changing the gain of signals conveyed between neurons. Here we examine synaptic plasticity between individual neocortical layer-5 pyramidal neurons. We show that an increase in the synaptic response, induced by pairing action-potential activity in pre- and postsynaptic neurons, was only observed when synaptic input occurred at low frequencies. This frequency-dependent increase in synaptic responses arises because of a redistribution of the available synaptic efficacy and not because of an increase in the efficacy. Redistribution of synaptic efficacy could represent a mechanism to change the content, rather than the gain, of signals conveyed between neurons.}, Author = {Markram, H. and Tsodyks, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Synapses;Research Support, Non-U.S. Gov't;21 Neurophysiology;Action Potentials;Neuronal Plasticity;Pyramidal Cells;Rats;Rats, Wistar;In Vitro;Evoked Potentials;Animals;Patch-Clamp Techniques;24 Pubmed search results 2008;Cerebral Cortex}, Medline = {96351070}, Month = {8}, Nlm_Id = {0410462}, Number = {6594}, Organization = {Department of Neurobiology, The Weizmann Institute for Science, Rehovot, Israel.}, Pages = {807-10}, Pubmed = {8752273}, Title = {Redistribution of synaptic efficacy between neocortical pyramidal neurons}, Uuid = {40E03AA4-2359-4D99-ACAC-09B749D54149}, Volume = {382}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/382807a0}} @article{Markram:1994, Abstract = {Simultaneous recordings of membrane voltage and concentration of intracellular Ca2+ ([Ca2+]i) were made in apical dendrites of layer 5 pyramidal cells of rat neocortex after filling dendrites with the fluorescent Ca2+ indicator Calcium Green-1. Subthreshold excitatory postsynaptic potentials (EP-SPs), mediated by the activation of glutamate receptor channels, caused a brief increase in dendritic [Ca2+]i. This rise in dendritic [Ca2+]i was mediated by the opening of low-voltage-activated Ca2+ channels in the dendritic membrane. The results provide direct evidence that dendrites do not function as passive cables even at low-frequency synaptic activity; rather, a single subthreshold EPSP changes the dendritic membrane conductance by opening Ca2+ channels and generating a [Ca2+]i transient that may propagate towards the soma. The activation of these Ca2+ channels at a low-voltage threshold is likely to influence the way in which dendritic EPSPs contribute to the electrical activity of the neuron.}, Author = {Markram, H. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Membrane Potentials;Neurons;Synapses;Dendrites;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Receptors, AMPA;Signal Transduction;Calcium;Calcium Channels;Rats, Wistar;Microscopy, Fluorescence;Animals;24 Pubmed search results 2008;Cerebral Cortex;Differential Threshold}, Medline = {94255500}, Month = {5}, Nlm_Id = {7505876}, Number = {11}, Organization = {Max-Planck-Institut f{\"u}r Medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Germany.}, Pages = {5207-11}, Pubmed = {8197208}, Title = {Calcium transients in dendrites of neocortical neurons evoked by single subthreshold excitatory postsynaptic potentials via low-voltage-activated calcium channels}, Uuid = {320FC852-6869-4368-97CC-EFDDE68F8E63}, Volume = {91}, Year = {1994}} @article{Markram:1998, Abstract = {The nature of information stemming from a single neuron and conveyed simultaneously to several hundred target neurons is not known. Triple and quadruple neuron recordings revealed that each synaptic connection established by neocortical pyramidal neurons is potentially unique. Specifically, synaptic connections onto the same morphological class differed in the numbers and dendritic locations of synaptic contacts, their absolute synaptic strengths, as well as their rates of synaptic depression and recovery from depression. The same axon of a pyramidal neuron innervating another pyramidal neuron and an interneuron mediated frequency-dependent depression and facilitation, respectively, during high frequency discharges of presynaptic action potentials, suggesting that the different natures of the target neurons underlie qualitative differences in synaptic properties. Facilitating-type synaptic connections established by three pyramidal neurons of the same class onto a single interneuron, were all qualitatively similar with a combination of facilitation and depression mechanisms. The time courses of facilitation and depression, however, differed for these convergent connections, suggesting that different pre-postsynaptic interactions underlie quantitative differences in synaptic properties. Mathematical analysis of the transfer functions of frequency-dependent synapses revealed supra-linear, linear, and sub-linear signaling regimes in which mixtures of presynaptic rates, integrals of rates, and derivatives of rates are transferred to targets depending on the precise values of the synaptic parameters and the history of presynaptic action potential activity. Heterogeneity of synaptic transfer functions therefore allows multiple synaptic representations of the same presynaptic action potential train and suggests that these synaptic representations are regulated in a complex manner. It is therefore proposed that differential signaling is a key mechanism in neocortical information processing, which can be regulated by selective synaptic modifications.}, Author = {Markram, H. and Wang, Y. and Tsodyks, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Synapses;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Pyramidal Cells;Rats, Wistar;In Vitro;Brain Mapping;Interneurons;Research Support, U.S. Gov't, Non-P.H.S.;Animals;Somatosensory Cortex;Synaptic Transmission;24 Pubmed search results 2008}, Medline = {98226813}, Month = {4}, Nlm_Id = {7505876}, Number = {9}, Organization = {Department of Neurobiology, The Weizmann Institute for Science, Rehovot, 76100, Israel. bnmark\@weizmann.weizmann.ac.il}, Pages = {5323-8}, Pubmed = {9560274}, Title = {Differential signaling via the same axon of neocortical pyramidal neurons}, Uuid = {C532346F-B356-46E2-AEA1-A0368647977B}, Volume = {95}, Year = {1998}} @article{Markram:1997b, Abstract = {Activity-driven modifications in synaptic connections between neurons in the neocortex may occur during development and learning. In dual whole-cell voltage recordings from pyramidal neurons, the coincidence of postsynaptic action potentials (APs) and unitary excitatory postsynaptic potentials (EPSPs) was found to induce changes in EPSPs. Their average amplitudes were differentially up- or down-regulated, depending on the precise timing of postsynaptic APs relative to EPSPs. These observations suggest that APs propagating back into dendrites serve to modify single active synaptic connections, depending on the pattern of electrical activity in the pre- and postsynaptic neurons. 0036-8075 Journal Article}, Author = {Markram, H. and Lubke, J. and Frotscher, M. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Science}, Keywords = {Dendrites/*physiology;Electric Stimulation;Animals;In Vitro;Up-Regulation;*Synaptic Transmission;Rats;Receptors, N-Methyl-D-Aspartate/metabolism;Synapses/*physiology;Patch-Clamp Techniques;Pyramidal Cells/*physiology;Rats, Wistar;M;Calcium/metabolism;Time Factors;Support, Non-U.S. Gov't;Action Potentials;Down-Regulation;18 Classic Neuroanatomy Physiology;Cerebral Cortex/cytology/physiology}, Number = {5297}, Organization = {Max-Planck-Institut fur Medizinische Forschung, Abteilung Zellphysiologie, Jahnstrasse 29, D-69120 Heidelberg, Germany. bnmark\@weizmann.weizmann.ac.il}, Pages = {213-5}, Pubmed = {8985014}, Title = {Regulation of synaptic efficacy by coincidence of postsynaptic APs and EPSPs}, Uuid = {795C5ED1-AD7C-4231-B3E8-BDA19FE21215}, Volume = {275}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8985014}} @article{Marodon:2003, Abstract = {Achieving cell-specific expression of a therapeutic transgene by gene transfer vectors represents a major goal for gene therapy. To achieve specific expression of a transgene in CD4(+) cells, we have generated lentiviral vectors expressing the enhanced green fluorescent protein (eGFP) reporter gene under the control of regulatory sequences derived from the CD4 gene--a minimal promoter and the proximal enhancer, with or without the silencer. Both lentiviral vectors could be produced at high titers (more than 10(7) infectious particles per milliliter) and were used to transduce healthy murine hematopoietic stem cells (HSCs). On reconstitution of RAG-2-deficient mice with transduced HSCs, the specific vectors were efficiently expressed in T cells, minimally expressed in B cells, and not expressed in immature cells of the bone marrow. Addition of the CD4 gene-silencing element in the vector regulatory sequences led to further restriction of eGFP expression into CD4(+) T cells in reconstituted mice and in ex vivo-transduced human T cells. Non-T CD4(+) dendritic and macrophage cells derived from human CD34(+) cells in vitro expressed the transgene of the specific vectors, albeit at lower levels than CD4(+) T cells. Altogether, we have generated lentiviral vectors that allow specific targeting of transgene expression to CD4(+) cells after differentiation of transduced mice HSCs and human mature T cells. Ultimately, these vectors may prove useful for in situ injections for in vivo gene therapy of HIV infection or genetic immunodeficiencies.}, Author = {Marodon, Gilles and Mouly, Enguerran and Blair, Emma J. and Frisen, Charlotte and Lemoine, Fran\c{c}ois M. and Klatzmann, David}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Cell Differentiation;Transduction, Genetic;Animals;DNA-Binding Proteins;Gene Expression Regulation;Humans;Lentivirus;Antigens, CD4;Mice, Inbred C57BL;Recombinant Fusion Proteins;11 Glia;Green Fluorescent Proteins;Radiation Chimera;Genes, Synthetic;Genetic Vectors;Bone Marrow Cells;Cell Lineage;Thymus Gland;Mice, Knockout;Adult;Regulatory Sequences, Nucleic Acid;Mice;CD4-Positive T-Lymphocytes;Luminescent Proteins;Genes, Reporter;Hematopoietic Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {22592439}, Month = {5}, Nlm_Id = {7603509}, Number = {9}, Organization = {Centre National de la Recherche Scientifique UMR-7087, Biologie et Th{\'e}rapeutique des Pathologies Immunitaires, Centre d'Etude et de Recherche en Virologie et en Immunologie, H\^{o}pital La Piti{\'e}-S\^{a}lp{\'e}tri\`{e}re, Paris, France.}, Pages = {3416-23}, Pii = {2002-02-0578}, Pubmed = {12511423}, Title = {Specific transgene expression in human and mouse CD4+ cells using lentiviral vectors with regulatory sequences from the CD4 gene}, Uuid = {A54BF6A1-6B32-4BDF-969A-FB71EE636972}, Volume = {101}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood-2002-02-0578}} @article{Marshall:2003, Abstract = {The subventricular zone (SVZ) of the perinatal forebrain gives rise to both neurons and glia. The mechanisms governing the phenotypic specification of progenitors within this heterogeneous germinal zone are unclear. However, the characterization of subpopulations of SVZ cells has given us a better understanding of the basic architecture of the SVZ and presents us with the opportunity to ask more detailed questions regarding phenotype specification and cell fate. Recent work demonstrating the embryonic origins of SVZ cells is summarized, and a model describing the formation of the perinatal SVZ, noting contributions of cells from pallial as well as subpallial germinal zones, is presented. We further address differences among classes of SVZ cells based on molecular profile, phenotype, and migration behavior and present a model summarizing the organization of perinatal SVZ cells along coronal, sagittal, and horizontal axes. A detailed description of the SVZ in the adult, outlining classes of cells based on morphology, molecular profile, and proliferative behavior, was recently reported by Doetsch et al. (Proc Natl Acad Sci USA 93:14895-14900, 1997). Potential relationships among cells within the perinatal and adult SVZ will be discussed. GLIA 43:52-61, 2003. 0894-1491 Journal Article Review Review, Academic}, Author = {Marshall, C. A. and Suzuki, S. O. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {Glia}, Keywords = {Prosencephalon/cytology/*embryology/*growth &development;02 Adult neurogenesis migration;Lateral Ventricles/cytology/*embryology/growth &development;Neuroglia/*cytology/physiology;Neurons/*cytology/physiology;Stem Cells/*cytology/physiology;Human;03 Adult neurogenesis progenitor source;Biological Markers;BB both;Cell Lineage/physiology;Cell Differentiation/physiology;Support, U.S. Gov't, P.H.S.;Animals;Cell Movement/physiology}, Number = {1}, Organization = {Center for Neurobiology and Behavior, Division of Neuropathology, Department of Pathology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.}, Pages = {52-61}, Pubmed = {12761867}, Title = {Gliogenic and neurogenic progenitors of the subventricular zone: who are they, where did they come from, and where are they going?}, Uuid = {32DAD1B5-4469-4245-863F-08049F5F04D0}, Volume = {43}, Year = {2003}, url = {papers/Marshall_Glia2003}} @article{Martens:2002, Abstract = {Stem cells isolated from the fourth ventricle and spinal cord form neurospheres in vitro in response to basic fibroblast growth factor (FGF2)+heparin (H) or epidermal growth factor (EGF)+FGF2 together. To determine whether these growth factor conditions are sufficient to induce stem cells within the fourth ventricle and spinal cord to proliferate and expand their progeny in vivo, we infused EGF and FGF2, alone or together, with or without H, into the fourth ventricle for 6 days via osmotic minipumps. Animals were injected with bromodeoxyuridine (BrdU) on days 4, 5 and 6 of infusion in order to label cells proliferating in response to the growth factors. Infusions of EGF+FGF2+H into the fourth ventricle resulted in the largest proliferative effect, a 10.8-fold increase in the number of BrdU+ cells around the fourth ventricle, and a 33.5-fold increase in the number of BrdU+ cells around the central canal of the spinal cord, as compared to vehicle infused controls. The majority of the cells were nestin+ after 6 days of infusion. Seven weeks post-infusion, 22 and 30\%of the number of BrdU+ cells induced to proliferate after 6 days of EGF+FGF2+H infusions were still detected around the fourth ventricle and central canal of the spinal cord, respectively. Analysis of the fates of the remaining cells showed that a small percentage of BrdU+ cells around the fourth ventricle and in the white matter of the spinal cord differentiated into astrocytes and oligodendrocytes. BrdU+ neurons were not found in the brainstem or in the grey matter of the cervical spinal cord 7 weeks post-infusion. These results show that endogenous stem cells and progenitors around the fourth ventricle and central canal of the spinal cord proliferate in response to exogenously applied growth factors, but unlike in the lateral ventricle where they generate some new neurons, they only produce new astrocytes and oligodendrocytes at 7 weeks post-infusion. 0953-816x Journal Article}, Author = {Martens, D. J. and Seaberg, R. M. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Eur J Neurosci}, Keywords = {Heparin/pharmacology;Animals;Lateral Ventricles/cytology/drug effects/metabolism;Cells, Cultured;Fourth Ventricle/*cytology/drug effects/metabolism;Spinal Cord/*cytology/drug effects/metabolism;Growth Substances/*pharmacology;Male;Injections, Intraventricular;Stem Cells/*cytology/drug effects/metabolism;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;Mice, Inbred Strains;Neuroglia/cytology/drug effects/metabolism;Neurons/*cytology/drug effects/metabolism;Cell Division/drug effects/*physiology;04 Adult neurogenesis factors;Fibroblast Growth Factor 2/pharmacology;Mice;Immunohistochemistry;C pdf;Rhombencephalon/*cytology/drug effects/metabolism;Up-Regulation/drug effects/physiology}, Number = {6}, Organization = {Department of Anatomy and Cell Biology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada. djmartens\@sympatico.ca}, Pages = {1045-57}, Pubmed = {12383233}, Title = {In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord}, Uuid = {107B0C44-E370-4A89-9EA8-3B0B14EB88C3}, Volume = {16}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12383233}} @article{Martens:2000, Abstract = {The embryonic forebrain germinal zone contains two separate and additive populations of epidermal growth factor (EGF)- and fibroblast growth factor (FGF)-responsive stem cells that both exhibit self-renewal and multipotentiality. Although cumulative S phase labeling studies have investigated the proliferation kinetics of the overall population of precursor cells within the forebrain germinal zone through brain development, little is known about when and how (symmetrically or asymmetrically) the small subpopulations of stem cells are proliferating in vivo. This has been determined by injecting timed-pregnant mice with high doses of tritiated thymidine ((3)H-thy) to kill any stem cells proliferating within the striatal germinal zone in vivo and then by assaying for neurosphere formation in vitro. Injections of 0.8 mCi of (3)H-thy given every 2 hr for 12 hr to timed-pregnant mice at E11, E14, and E17 resulted in significant depletions in the number of neurospheres generated by FGF-responsive stem cells at E11 and by EGF-responsive and FGF-responsive stem cells at E14 and E17. With increasing embryonic age, the depletions observed in the number of neurospheres generated in vitro in response to FGF2 after exposure to (3)H-thy in vivo decreased, suggesting there is an increase in the length of the cell cycle of FGF-responsive neural stem cells through embryonic development. The results suggest that the FGF-responsive stem cell population expands between E11 and E14 by dividing symmetrically, but switches to primarily asymmetric division between E14 and E17. The EGF-responsive stem cells arise after E11, and their population expands through symmetric divisions and through asymmetric divisions of FGF-responsive stem cells. 20115704 1529-2401 Journal Article}, Author = {Martens, D. J. and Tropepe, V. and van Der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {J Neurosci}, Keywords = {Prosencephalon/*embryology;Drug Administration Schedule;Neurons/*cytology/metabolism;Embryo/cytology/metabolism;Stem Cells/*cytology/metabolism;Epidermal Growth Factor/*pharmacology;Animal;Cell Count;Kinetics;Corpus Striatum/embryology;Fibroblast Growth Factors/*pharmacology;DNA/metabolism;Cell Division/drug effects/physiology;Thymidine/administration &dosage/metabolism;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Mice;Injections;C-18}, Number = {3}, Organization = {University of Toronto, Department of Anatomy and Cell Biology, Toronto, Ontario M5S 1A8, Canada. david.martens\@utoronto.ca}, Pages = {1085-95}, Pubmed = {10648714}, Title = {Separate proliferation kinetics of fibroblast growth factor-responsive and epidermal growth factor-responsive neural stem cells within the embryonic forebrain germinal zone}, Uuid = {87E9034E-01B1-4B29-8BA5-954DA67FD3E5}, Volume = {20}, Year = {2000}, url = {papers/Martens_JNeurosci2000.pdf}} @article{Martin:2001, Abstract = {Episodes of prolonged seizures or head trauma produce chronic hippocampal network hyperexcitability hypothesized to result primarily from inhibitory interneuron loss or dysfunction. The possibly causal role of inhibitory neuron failure in the development of epileptiform pathophysiology remains unclear because global neurologic injuries produce such a multitude of effects. The recent finding that Substance P receptors (SPRs) are expressed exclusively in the rat hippocampus by inhibitory interneurons provided the rationale for attempting to ablate interneurons selectively by using neurotoxic conjugates of SPR ligands and the ribosome inactivating protein saporin that specifically target Substance P receptor-expressing cells. Whereas intrahippocampal microinjection of a conjugate of native SP and saporin produced significant nonspecific damage at concentrations needed to produce even limited selective loss of SPR-positive cells, a conjugate of saporin and the more potent and peptidase-resistant SP analog [Sar(9), Met(O(2))(11)] Substance P (SSP-saporin) caused negligible nonspecific damage at the injection site, and a virtually complete loss of SPR-like immunoreactivity (LI) up to 1 mm from the injection site. Within the SPR depletion zone, immunoreactivities for most GABA-, parvalbumin-, somatostatin-, and cholecystokinin-immunoreactive cells and fibers were eliminated. The few interneurons detectable within the affected zone were devoid of SPR-LI. The apparent loss of interneurons was selective in that calbindin- and glutamate receptor subunit 2 (GluR2) -positive principal cells survived within the affected zone, as did myelinated fibers and the extrinsic calretinin- and tyrosine hydroxylase--immunoreactive terminals of subcortical afferents. An apparent lack of reactive synaptic reorganization in response to interneuron loss was indicated by zinc transporter-3 (ZnT3)-- and beta-synuclein--LI, as well as by Timm staining, all of which revealed relatively normal patterns of excitatory terminal distribution. Control injections produced minor damage at the injection site, but no apparent specific loss of SPR-LI. One to 12 weeks after injection of SSP-saporin, extracellular electrophysiological field responses recorded in the CA1 pyramidal and dentate granule cell layers in response to afferent stimulation were blindly evaluated simultaneously in two sites 1-2 mm apart along the longitudinal hippocampal axis. SSP-saporin-treated rats exhibited relatively normal responses in some sites, whereas disinhibition and hyperexcitability indistinguishable from the pathophysiology produced by experimental status epilepticus were simultaneously recorded at adjacent sites. Anatomic analysis of the recording sites in each animal revealed that epileptiform pathophysiology was consistently observed only within areas of SPR ablation, whereas relatively normal evoked responses were recorded from immediately adjacent and relatively unaffected regions. These data establish the efficacy of [Sar(9), Met(O(2))(11)] Substance P-saporin for producing a selective and spatially extensive ablation of hippocampal inhibitory interneurons in vivo and a highly focal disinhibition that was restricted to the site of interneuron loss. These results also demonstrate that the "epileptic" pathophysiology produced by experimental status epilepticus or head trauma can be replicated by focal interneuron loss per se, without involving principal cell loss and other interpretive confounds inherent in the use of global neurologic injury models.}, Author = {Martin, J. L. and Sloviter, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {N-Glycosyl Hydrolases;Antineoplastic Agents, Phytogenic;Neurotoxins;Animals;Rats;Neuronal Plasticity;Peptide Hydrolases;21 Epilepsy;Immunotoxins;Epilepsy;Rats, Sprague-Dawley;Plant Proteins;Hippocampus;Pyramidal Cells;Male;Research Support, U.S. Gov't, P.H.S.;Peptide Fragments;Nerve Net;Receptors, Neurokinin-1;21 Neurophysiology;Mossy Fibers, Hippocampal;Membrane Potentials;Interneurons;24 Pubmed search results 2008;Immunohistochemistry;Neural Inhibition;Cell Death;Substance P;Glial Fibrillary Acidic Protein}, Medline = {21331787}, Month = {7}, Nlm_Id = {0406041}, Number = {2}, Organization = {Department of Pharmacology, University of Arizona College of Medicine, Tucson, Arizona 85724, USA.}, Pages = {127-52}, Pubmed = {11438920}, Title = {Focal inhibitory interneuron loss and principal cell hyperexcitability in the rat hippocampus after microinjection of a neurotoxic conjugate of saporin and a peptidase-resistant analog of Substance P}, Uuid = {40CDD2E7-94DD-4851-9E46-87FB4A536881}, Volume = {436}, Year = {2001}} @article{Martinez:2005, Abstract = {Here we ask whether visual response pattern varies with position in the cortical microcircuit by comparing the structure of receptive fields recorded from the different layers of the cat's primary visual cortex. We used whole-cell recording in vivo to show the spatial distribution of visually evoked excitatory and inhibitory inputs and to stain individual neurons. We quantified the distribution of 'On' and 'Off' responses and the presence of spatially opponent excitation and inhibition within the receptive field. The thalamorecipient layers (4 and upper 6) were dominated by simple cells, as defined by two criteria: they had separated On and Off subregions, and they had push-pull responses (in a given subregion, stimuli of the opposite contrast evoked responses of the opposite sign). Other types of response profile correlated with laminar location as well. Thus, connections unique to each visual cortical layer are likely to serve distinct functions.}, Author = {Martinez, Luis M. and Wang, Qingbo and Reid, R. Clay and Pillai, Cinthi and Alonso, Jos{\'e}-Ma\~{n}uel M. and Sommer, Friedrich T. and Hirsch, Judith A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Models, Neurological;Neural Inhibition;Electrophysiology;Photic Stimulation;Animals;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Visual Pathways;Reaction Time;comparative study ;Visual Fields;Thalamus;Action Potentials;Neurons;21 Neurophysiology;24 Pubmed search results 2008;Visual Cortex;Cats;Geniculate Bodies;Brain Mapping}, Month = {3}, Nlm_Id = {9809671}, Number = {3}, Organization = {Department of Medicine, Campus de Oza, Universidad A Coru\~{n}a, 15006, Spain.}, Pages = {372-9}, Pii = {nn1404}, Pubmed = {15711543}, Title = {Receptive field structure varies with layer in the primary visual cortex}, Uuid = {7931C83B-81AE-44F3-A484-BB0518A1F078}, Volume = {8}, Year = {2005}, url = {papers/Martinez_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1404}} @article{Martinez-Marcos:2005, Abstract = {The location of neurogenesis and the direction of migration of neurons in the adult mouse vomeronasal organ is controversial. Cell division occurs at the center, and particularly, at the edges of the epithelium. Newly generated cells at the center of the epithelium participate in neurogenesis, however, it is unknown to what extent dividing cells at the edges participate in growth, become apoptotic or mature into neurons. Premitotic cells were labeled with bromodeoxyuridine (BrdU) in adult mice and animals allowed to survive for different postinjection periods. The terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end-labeling (TUNEL) method was used to show the distribution of apoptotic cells. The vertical and horizontal position of BrdU-labeled cells was analyzed as a function of postinjection survival time. Vertical and horizontal migration of BrdU-labeled cells were detected. Cells in the central portions of the epithelium migrated vertically to become neurons as demonstrated by co-expression of olfactory marker protein. Cells at the edges migrated horizontally very slowly (less than 10\%of the distance from the edge to the center of the epithelium per month), thus indicating that these cells participate in cell renewal exclusively in marginal regions. Neural turnover in the mouse vomeronasal epithelium, therefore appears to occur through a process of vertical migration. Data on the distribution of apoptotic cells indicate that a number of dividing cells throughout the epithelium, but particularly at the edges, die before becoming functional neurons. Accordingly, most dividing cells at the edges probably constitute a reservoir of stem cells dying before differentiation. (c) 2005 Wiley Periodicals, Inc. J Neurobiol, 2005.}, Author = {Martinez-Marcos, and Jia, and Quan, and Halpern,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0213640}, Organization = {Departamento de Ciencias M{\'e}dicas, Facultad de Medicina, Centro Regional de Investigaci{\'o}n Biom{\'e}dica, Universidad de Castillala Mancha, Avda. Almansa S/N, 02006 Albacete, Spain.}, Pubmed = {15729685}, Title = {Neurogenesis, migration, and apoptosis in the vomeronasal epithelium of adult mice}, Uuid = {A3849F76-97AC-46FB-BA62-6E106AB8D53A}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.20128}} @article{Martin:2001a, Abstract = {Human immunodeficiency virus type 1 (HIV-1) infects and induces syncytium formation in microglial cells from the central nervous system (CNS). A primary isolate (HIV-1(BORI)) was sequentially passaged in cultured microglia, and the isolate recovered (HIV-1(BORI-15)) showed high levels of fusion and replicated more efficiently in microglia (J. M. Strizki, A. V. Albright, H. Sheng, M. O'Connor, L. Perrin, and F. Gonz{\'a}lez-Scarano, J. Virol. 70:7654-7662, 1996). The parent and adapted viruses used CCR5 as coreceptor. Recombinant viruses demonstrated that the syncytium-inducing phenotype was associated with four amino acid differences in the V1/V2 region of the viral gp120 (J. T. C. Shieh, J. Martin, G. Baltuch, M. H. Malim, and F. Gonz{\'a}lez-Scarano, J. Virol. 74:693-701, 2000). We produced luciferase-reporter, env-pseudotyped viruses using plasmids containing env sequences from HIV-1(BORI), HIV-1(BORI-15), and the V1/V2 region of HIV-1(BORI-15) in the context of HIV-1(BORI) env (named rBORI, rB15, and rV1V2, respectively). The pseudotypes were used to infect cells expressing various amounts of CD4 and CCR5 on the surface. In contrast to the parent recombinant, the rB15 and rV1V2 pseudotypes retained their infectability in cells expressing low levels of CD4 independent of the levels of CCR5, and they infected cells expressing CD4 with a chimeric coreceptor containing the third extracellular loop of CCR2b in the context of CCR5 or a CCR5 Delta4 amino-terminal deletion mutant. The VH-rB15 and VH-rV1V2 recombinant viruses were more sensitive to neutralization by a panel of HIV-positive sera than was VH-rBORI. Interestingly, the CD4-induced 17b epitope on gp120 was more accessible in the rB15 and rV1V2 pseudotypes than in rBORI, even before CD4 binding, and concomitantly, the rB15 and rV1V2 pseudotypes were more sensitive to neutralization with the human 17b monoclonal antibody. Adaptation to growth in microglia--cells that have reduced expression of CD4 in comparison with other cell types--appears to be associated with changes in gp120 that modify its ability to utilize CD4 and CCR5. Changes in the availability of the 17b epitope indicate that these affect conformation. These results imply that the process of adaptation to certain tissue types such as the CNS directly affects the interaction of HIV-1 envelope glycoproteins with cell surface components and with humoral immune responses.}, Author = {Mart{\'\i}n, J. and LaBranche, C. C. and Gonz{\'a}lez-Scarano, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Immune Sera;HIV-1;Adaptation, Biological;Cells, Cultured;Humans;Transfection;Brain;Microglia;HIV Antibodies;Serial Passage;Antigens, CD4;11 Glia;Cell Line;Research Support, U.S. Gov't, P.H.S.;Sequence Deletion;Chimeric Proteins;Antibodies, Monoclonal;Receptors, Chemokine;Epitopes;Neutralization Tests;Receptors, CCR5;Enzyme-Linked Immunosorbent Assay;Genes, Reporter;HIV Envelope Protein gp120;Luciferases}, Medline = {21165267}, Month = {4}, Nlm_Id = {0113724}, Number = {8}, Organization = {Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.}, Pages = {3568-80}, Pubmed = {11264346}, Title = {Differential CD4/CCR5 utilization, gp120 conformation, and neutralization sensitivity between envelopes from a microglia-adapted human immunodeficiency virus type 1 and its parental isolate}, Uuid = {9F7628F0-2472-4F89-8263-7987F5A6F2F6}, Volume = {75}, Year = {2001}, url = {papers/Martín_JVirol2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.75.8.3568-3580.2001}} @article{Martin-Garcia:2006, Abstract = {We previously described envelope glycoproteins of an HIV-1 isolate adapted in vitro for growth in microglia that acquired a highly fusogenic phenotype and lower CD4 dependence, as well as resistance to inhibition by anti-CD4 antibodies. Here, we investigated whether similar phenotypic changes are present in vivo. Envelope clones from the brain and spleen of an HIV-1-infected individual with neurological disease were amplified, cloned, and sequenced. Phylogenetic analysis demonstrated clustering of sequences according to the tissue of origin, as expected. Functional clones were then used in cell-to-cell fusion assays to test for CD4 and co-receptor utilization and for sensitivity to various antibodies and inhibitors. Both brain- and spleen-derived envelope clones mediated fusion in cells expressing both CD4 and CCR5 and brain envelopes also used CCR3 as co-receptor. We found that the brain envelopes had a lower CD4 dependence, since they efficiently mediated fusion in the presence of low levels of CD4 on the target cell membrane, and they were significantly more resistant to blocking by anti-CD4 antibodies than the spleen-derived envelopes. In contrast, we observed no difference in sensitivity to the CCR5 antagonist TAK-779. However, brain-derived envelopes were significantly more resistant than those from spleen to the fusion inhibitor T-1249 and concurrently showed slightly greater fusogenicity. Our results suggest an increased affinity for CD4 of brain-derived envelopes that may have originated from in vivo adaptation to replication in microglial cells. Interestingly, we note the presence of envelopes more resistant to a fusion inhibitor in the brain of an untreated, HIV-1-infected individual.}, Author = {Mart{\'\i}n-Garc{\'\i}a, Julio and Cao, Wei and Varela-Rohena, Angel and Plassmeyer, Matthew L. and Gonz{\'a}lez-Scarano, Francisco}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {HIV Fusion Inhibitors;Receptors, HIV;HIV Infections;Molecular Sequence Data;HIV-1;Membrane Fusion;AIDS Dementia Complex;HIV Envelope Protein gp41;Research Support, N.I.H., Extramural;Amino Acid Sequence;Antigens, CD4;11 Glia;Humans;Brain;Spleen;Drug Resistance, Viral;HIV Envelope Protein gp120}, Month = {3}, Nlm_Id = {0110674}, Number = {1}, Organization = {Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. julio.martin-garcia\@drexelmed.edu}, Pages = {169-79}, Pii = {S0042-6822(05)00726-9}, Pubmed = {16309726}, Title = {HIV-1 tropism for the central nervous system: Brain-derived envelope glycoproteins with lower CD4 dependence and reduced sensitivity to a fusion inhibitor}, Uuid = {6BEF24CF-6A1E-4CFB-8FA2-DCF80FE7AA86}, Volume = {346}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.virol.2005.10.031}} @article{Martinez-Cerdeno:2006, Abstract = {The vertebrate cerebral cortex varies from the 3-layered dorsal cortex of reptiles to the 6-layered lissencephalic cortex characteristic of rodents and to the 6-layered gyrencephalic cortex typical of carnivores and primates. Distinct developmental mechanisms may have evolved independently to account for the radial expansion that produced the multilayered cortex of mammals and for the tangential expansion of cortical surface area that resulted in gyrencephalic cortex. Recent evidence shows that during the late stages of cortical development, radial glial cells divide asymmetrically in the ventricular zone to generate radial glial cells and intermediate progenitor (IP) cells and that IP cells subsequently divide symmetrically in the subventricular zone to produce multiple neurons. We propose that the evolution of this two-step pattern of neurogenesis played an important role in the amplification of cell numbers underlying the radial and tangential expansion of the cerebral cortex.}, Author = {Mart{\'\i}nez-Cerde\~{n}o, Ver{\'o}nica and Noctor, Stephen C. and Kriegstein, Arnold R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {9110718}, Number = {Suppl 1}, Organization = {Department of Neurology and the Institute for Stem Cell and Tissue Biology, University of California-San Francisco, San Francisco, CA 94143, USA.}, Pages = {i152-i161}, Pii = {16/suppl_1/i152}, Pubmed = {16766701}, Title = {The role of intermediate progenitor cells in the evolutionary expansion of the cerebral cortex}, Uuid = {57B58582-BADF-4786-81A4-0B48D42B7ED1}, Volume = {16}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhk017}} @article{Martinez-Contreras:2002, Abstract = {Recent studies confirm that astrocytes and neurons are associated with the synaptic transmission, particularly with the regulation of glutamate (Glu) levels. Therefore, they have the capacity to modulate the Glu released from neurons into the extracellular space. It has also been demonstrated an intense astrocytic and microglia response to physical or chemical lesions of the central nervous system. However, the persistence of the response of the glial cells in adult brain had not been previously reported, after the excitotoxic damage caused by neonatal dosage of monosodium glutamate (MSG) to newborn rats. In this study, 4 mg/g body weight of MSG were administered to newborn rats at 1, 3, 5, and 7 days after birth, at the age of 60 days the astrocytes and the microglia cells were analyzed with immunohistochemical methods in the fronto-parietal cortex. Double labeling to glial fibrillary acidic protein (GFAP) and BrdU, or isolectin-B(4) and BrdU identified astrocytes or microglia cells that proliferated; immunoblotting and immunoreactivity to vimentin served for assess immaturity of astrocytic intermediate filaments. The results show that the neonatal administration of MSG-induced reactivity of astrocytes and microglia cells in the fronto-parietal cortex, which was characterized by hyperplasia; an increased number of astrocytes and microglia cells that proliferated, hypertrophy; increased complexity of the cytoplasm extension of both glial cells and expression of RNAm to vimentin, with the presence of vimentin-positive astrocytes. This glial response to neuroexcitotoxic stimulus of Glu on the immature brain, which persisted to adulthood, suggests that the neurotransmitter Glu could trigger neuro-degenerative illnesses.}, Author = {Mart{\'\i}nez-Contreras, A. and Huerta, M. and Lopez-Perez, S. and Garc{\'\i}a-Estrada, J. and Luqu{\'\i}n, S. and Beas Z{\'a}rate, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Research Support, Non-U.S. Gov't;Neurotoxins;Astrocytes;Animals;Aging;Rats;Fluorescent Antibody Technique;Glutamic Acid;Synaptic Transmission;Microglia;Female;Vimentin;Rats, Wistar;Disease Models, Animal;Male;Animals, Newborn;Cerebral Cortex;Gliosis;Neurodegenerative Diseases;Cell Division;24 Pubmed search results 2008;Stem Cells;Bromodeoxyuridine;Lectins;Glial Fibrillary Acidic Protein}, Medline = {21642404}, Month = {1}, Nlm_Id = {7600111}, Number = {2}, Organization = {Lab de Neuroqu{\'\i}mica, Div de Neurociencias, C.I.B.O., Guadalajara Jal., Mexico.}, Pages = {200-10}, Pii = {10.1002/jnr.10093}, Pubmed = {11782964}, Title = {Astrocytic and microglia cells reactivity induced by neonatal administration of glutamate in cerebral cortex of the adult rats}, Uuid = {3944E797-5B2A-42E6-84CF-994951B8224E}, Volume = {67}, Year = {2002}} @article{Masahira:2006, Abstract = {Motoneurons and oligodendrocytes in the embryonic spinal cord are produced from a restricted domain of the ventral ventricular zone, termed the pMN domain. The pMN domain is the site of expression of two basic helix-loop-helix transcription factors, Olig1 and Olig2, which are essential for motoneuron and oligodendrocyte development. Previous lineage-tracing experiments using Olig1-Cre and Olig2-GFP mice suggested that motoneurons and oligodendrocytes, but not astrocytes, are produced from the pMN domain. However, important questions remain, including the fate of neuroepithelial cells in the pMN domain, and specifically whether motoneurons and oligodendrocytes are the only types of cells produced in the pMN domain. We performed lineage-tracing experiments using a tamoxifen-inducible Cre-recombinase inserted into the Olig2 locus. We demonstrated that motoneurons and oligodendrocyte progenitors are derived from the Olig2(+) progenitors in the pMN domain, and also found that a subset of astrocytes at the ventral surface of the spinal cord and ependymal cells at the ventricular surface are also produced from the pMN domain. These findings demonstrate that motoneurons and oligodendrocytes are not the only cell types originating from this domain.}, Author = {Masahira, and Takebayashi, and Ono, and Watanabe, and Ding, and Furusho, and Ogawa, and Nabeshima, and Alvarez-Buylla, and Shimizu, and Ikenaka,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {0372762}, Organization = {Division of Neurobiology and Bioinformatics, National Institute for Physiological Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan; Department of Neurosurgery, Kochi Medical School, Nankoku 783-8505, Japan.}, Pii = {S0012-1606(06)00126-6}, Pubmed = {16581057}, Title = {Olig2-positive progenitors in the embryonic spinal cord give rise not only to motoneurons and oligodendrocytes, but also to a subset of astrocytes and ependymal cells}, Uuid = {BD702F19-08AE-461D-B96C-6BEA64DA9FDB}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2006.02.029}} @article{Masland:2001, Abstract = {The listing of cell types present in the retina is nearing completion, the first time this can be said for any significantly complex sample of the central nervous system. Mammalian retinas contain approximately 55 separate neuronal types. The functions of 22 of them are known or can be strongly inferred. For these 22, in every instance, a cell defined as a 'type' by structural criteria carries out a distinct and individual physiological function. Electrophysiological experiments continue to reveal new features of the retina's handling of information, and there is every reason to believe that the remaining 33 types of cell will also have distinct physiological functions. Further subtleties clearly exist in both peripheral and central visual coding.}, Author = {Masland, R. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Retina;21 Neurophysiology;research support, non-u.s. gov't ;Photoreceptors, Vertebrate;Retinal Ganglion Cells;Animals;24 Pubmed search results 2008;Neurons;review}, Month = {8}, Nlm_Id = {9111376}, Number = {4}, Organization = {Howard Hughes Medical Institute, Massachusetts General Hospital, Boston, MA 02114, USA. masland\@helix.mgh.harvard.edu}, Pages = {431-6}, Pii = {S0959-4388(00)00230-0}, Pubmed = {11502388}, Title = {Neuronal diversity in the retina}, Uuid = {AE36B435-B131-4191-A912-F60D5E81C14C}, Volume = {11}, Year = {2001}} @article{Masland:2001a, Abstract = {The retina, like many other central nervous system structures, contains a huge diversity of neuronal types. Mammalian retinas contain approximately 55 distinct cell types, each with a different function. The census of cell types is nearing completion, as the development of quantitative methods makes it possible to be reasonably confident that few additional types exist. Although much remains to be learned, the fundamental structural principles are now becoming clear. They give a bottom-up view of the strategies used in the retina's processing of visual information and suggest new questions for physiological experiments and modeling.}, Author = {Masland, R. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Retina;Cones (Retina);21 Neurophysiology;Color Perception;Retinal Ganglion Cells;Animals;Primates;Visual Pathways;review;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Howard Hughes Medical Institute, Wellman 429, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114, USA. masland\@helix.mgh.harvard.edu}, Pages = {877-86}, Pii = {nn0901-877}, Pubmed = {11528418}, Title = {The fundamental plan of the retina}, Uuid = {4E986A38-B957-44E8-866C-7FCC97EC3E69}, Volume = {4}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0901-877}} @article{Maslov:2004, Abstract = {The mammalian brain contains neural stem cells (NSCs) that allow continued neurogenesis throughout the life of the animal. However, neurogenesis is known to decline during aging and, to the extent that neurogenesis is required for normal CNS function, this may contribute to neurodegenerative disease. Decreased neurogenesis could result from loss of NSCs or dysfunction at some later step, and distinguishing these possibilities is important for understanding the cause of the decline. However, because of the inability to distinguish NSCs from their rapidly dividing progeny in situ, it has not been possible to quantitatively assess the NSC populations in young and old animals. In this report we show that the G1 phase-specific expression of the replication factor Mcm2 is a useful marker for detecting slowly cycling putative NSCs in situ and confirm the identity of these cells using both cytosine beta-D-arabinofuranoside (Ara-C) treatment and a double nucleoside analog-labeling technique. The ability to distinguish NSCs from proliferative progenitors has allowed characterization of the expression of several markers including Nestin, Musashi, and GFAP in these different cell types. Furthermore, comparison of the NSC populations in the subventricular zones of young (2-4 months) and old (24-26 months) mice demonstrates an approximately twofold reduction in the older mice. A similar twofold reduction is also observed in the number of neurospheres recovered in culture from old relative to young animals. The reduction in the neural stem cell population documented here is sufficient to account for the reduced level of neurogenesis in old animals. 1529-2401 Journal Article}, Author = {Maslov, A. Y. and Barone, T. A. and Plunkett, R. J. and Pruitt, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {J Neurosci}, Keywords = {B pdf;02 Adult neurogenesis migration}, Number = {7}, Organization = {Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA.}, Pages = {1726-33}, Title = {Neural stem cell detection, characterization, and age-related changes in the subventricular zone of mice}, Uuid = {9486AD80-D4D3-4A47-B89D-9E3572EA82AE}, Volume = {24}, Year = {2004}, url = {papers/Maslov_JNeurosci2004.pdf}} @article{Maslov:2007, Abstract = {Previous studies have demonstrated expression of the minichromosome maintenance protein Mcm2 in cells that remain competent to divide, including stem/progenitor cells of the subventricular zone (SVZ) within the brain. Here, a transgenic mouse line in which the Mcm2 gene drives expression of enhanced green fluorescent protein (EGFP) was constructed by insertion of an internal ribosomal entry site (IRES)-EGFP cassette into the last exon of the gene, 3' to the stop codon. In these mice, expression of EGFP is observed in the SVZ and several other tissues with high proliferative activity, including the spleen, intestine, hair follicles, and bone marrow. These observations suggest that EGFP fluorescence in this mouse line provides an index of the proliferative capacity of different tissues. Immunohistological analysis demonstrates a direct concordance between expression of EGFP and Mcm2, consistent with a transcriptional level downregulation of Mcm2 expression in postmitotic cells. To test the utility of EGFP expression for recovery of live cells retaining the capacity to divide, EGFP-expressing and -nonexpressing cells from bone marrow and brain were isolated from an adult Mcm2(IRES-EGFP) mouse by fluorescence-activated cell sorting and assayed for clonal growth. The EGFP-positive fraction contained the entire clonogenic population of the bone marrow and greater than 90\%of neurosphere-forming cells from the brain. Brain-derived clonogenic cells were shown to remain competent to differentiate towards all three neural lineages. These studies demonstrate that the Mcm2(IRES-EGFP) transgenic line constructed here can be used for recovery of proliferation competent cells from different tissue types.}, Author = {Maslov, Alexander Y. and Bailey, Kimberly J. and Mielnicki, Lawrence M. and Freeland, Amy L. and Sun, Xiaolei and Burhans, William C. and Pruitt, Steven C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {9304532}, Number = {1}, Organization = {Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York, New York 14263, USA. steven.pruitt\@roswellpark.org.}, Pages = {132-8}, Pii = {2006-0032}, Pubmed = {17008428}, Title = {Stem/Progenitor cell-specific enhanced green fluorescent protein expression driven by the endogenous mcm2 promoter}, Uuid = {50C3CA8B-6A51-4A8A-A535-89C22D2DB78D}, Volume = {25}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1634/stemcells.2006-0032}} @article{Mason:2001, Abstract = {Neuronal migration is an essential developmental step in the construction of the vertebrate nervous system, but the extracellular signals involved in initiating and regulating neuronal movement remain unclear. Here we report the identification of a novel astrocyte-derived migration-inducing activity (MIA). Using an in vitro assay, we show that MIA induces the migration of olfactory bulb interneuron precursors, increasing the number of migrating cells and the distance they move. We established quantitative criteria to distinguish between the biological effects of inducers, inhibitors, repellents, and attractants on migrating cells and used them to compare the effects of MIA with those of Slit, a putative repulsive guidance cue. Our analysis demonstrates that, by themselves, MIA induces and Slit inhibits migration from subventricular zone explants. However, when presented together with MIA, Slit acts as a repellent. This study shows that glial cells play a critical role in initiating and modulating the movement of neuronal precursors through the release of a diffusible protein. Moreover, this study provides evidence that the guidance of migrating neuronal precursors is an integrative process, resulting from the cooperation of distinct extracellular factors, and that the function of Slit is context dependent.}, Author = {Mason, H. A. and Ito, S. and Corfas, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Journal = {J Neurosci}, Keywords = {Extracellular Space/*metabolism;Dose-Response Relationship, Drug;Rats, Long-Evans;Interneurons/cytology/*metabolism;Cells, Cultured;Rats;Cell Movement/drug effects/*physiology;Models, Biological;Animal;02 Adult neurogenesis migration;B pdf;Olfactory Bulb/cytology/*metabolism;Nerve Tissue Proteins/metabolism/pharmacology;Signal Transduction/drug effects/physiology;Culture Media, Conditioned/pharmacology;Support, Non-U.S. Gov't;Growth Substances/pharmacology;Lateral Ventricles/cytology;Stem Cells/cytology/drug effects/*metabolism;Support, U.S. Gov't, P.H.S.;Cell Migration Inhibition;Chemotactic Factors/metabolism/pharmacology;Neuroglia/cytology/metabolism}, Number = {19}, Organization = {Division of Neuroscience and Department of Neurology, Children's Hospital and Harvard Medical School, Boston Massachusetts 02115, USA.}, Pages = {7654-63.}, Title = {Extracellular signals that regulate the tangential migration of olfactory bulb neuronal precursors: inducers, inhibitors, and repellents}, Uuid = {B4793014-9059-4D8C-841A-CD60A9E0EF37}, Volume = {21}, Year = {2001}, url = {papers/Mason_JNeurosci2001}} @article{Massague:2000, Author = {Massague, J. and Blain, S. W. and Lo, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Cell}, Keywords = {Models, Biological;Neoplasms/etiology;Hereditary Diseases/etiology;Human;Cell Division/genetics;C-15;Signal Transduction/*genetics;Transforming Growth Factor beta/*metabolism;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Cell Differentiation/genetics}, Number = {2}, Organization = {Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan- Kettering Cancer Center, New York, New York 10021, USA. j- massague\@ski.mskcc.org}, Pages = {295-309.}, Title = {TGFbeta signaling in growth control, cancer, and heritable disorders}, Uuid = {60143CA6-F0DE-4ADB-B81D-C542065B2BA5}, Volume = {103}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11057902}} @article{Massengale:2005, Abstract = {Several studies have reported that bone marrow (BM) cells may give rise to neurons and astrocytes in vitro and in vivo. To further test this hypothesis, we analyzed for incorporation of neural cell types expressing donor markers in normal or injured brains of irradiated mice reconstituted with whole BM or single, purified c-kit(+)Thy1.1(lo)Lin(-)Sca-1(+) (KTLS) hematopoietic stem cells (HSCs), and of unirradiated parabionts with surgically anastomosed vasculature. Each model showed low-level parenchymal engraftment of donor-marker(+) cells with 96-100\%immunoreactivity for panhematopoietic (CD45) or microglial (Iba1 or Mac1) lineage markers in all cases studied. Other than one arborizing structure in the olfactory bulb of one BM-transplanted animal, possibly representing a neuronal or glial cell process, we found no donor-marker-expressing astrocytes or non-Purkinje neurons among >10,000 donor-marker(+) cells from 21 animals. These data strongly suggest that HSCs and their progeny maintain lineage fidelity in the brain and do not adopt neural cell fates with any measurable frequency.}, Author = {Massengale, Mei and Wagers, Amy J. and Vogel, Hannes and Weissman, Irving L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-1007}, Journal = {J Exp Med}, Keywords = {08 Aberrant cell cycle;22 Stem cells}, Month = {5}, Nlm_Id = {2985109R}, Number = {10}, Organization = {Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305.}, Pages = {1579-89}, Pii = {jem.20050030}, Pubmed = {15897275}, Title = {Hematopoietic cells maintain hematopoietic fates upon entering the brain}, Uuid = {BFCE77E0-DB37-4096-8A56-49C3D9776C2D}, Volume = {201}, Year = {2005}, url = {papers/Massengale_JExpMed2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1084/jem.20050030}} @article{Massimini:2007, Abstract = {During much of sleep, cortical neurons undergo near-synchronous slow oscillation cycles in membrane potential, which give rise to the largest spontaneous waves observed in the normal electroencephalogram (EEG). Slow oscillations underlie characteristic features of the sleep EEG, such as slow waves and spindles. Here we show that, in sleeping subjects, slow waves and spindles can be triggered noninvasively and reliably by transcranial magnetic stimulation (TMS). With appropriate stimulation parameters, each TMS pulse at <1 Hz evokes an individual, high-amplitude slow wave that originates under the coil and spreads over the cortex. TMS triggering of slow waves reveals intrinsic bistability in thalamocortical networks during non-rapid eye movement sleep. Moreover, evoked slow waves lead to a deepening of sleep and to an increase in EEG slow-wave activity (0.5-4.5 Hz), which is thought to play a role in brain restoration and memory consolidation.}, Author = {Massimini, Marcello and Ferrarelli, Fabio and Esser, Steve K. and Riedner, Brady A. and Huber, Reto and Murphy, Michael and Peterson, Michael J. and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, non-u.s. gov't;Adult;21 Neurophysiology;Wakefulness;clinical trial;Transcranial Magnetic Stimulation;Humans;Male;Cerebral Cortex;Sleep;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {7505876}, Number = {20}, Organization = {Department of Psychiatry, University of Wisconsin, 6001 Research Park Boulevard, Madison, WI 53719, USA.}, Pages = {8496-501}, Pii = {0702495104}, Pubmed = {17483481}, Title = {Triggering sleep slow waves by transcranial magnetic stimulation}, Uuid = {A7086623-5826-446F-AE77-DD3AC973C14E}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0702495104}} @article{Massimini:2005, Abstract = {When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premotor area) is transmitted to the rest of the brain. During quiet wakefulness, an initial response (approximately 15 milliseconds) at the stimulation site was followed by a sequence of waves that moved to connected cortical areas several centimeters away. During non-rapid eye movement sleep, the initial response was stronger but was rapidly extinguished and did not propagate beyond the stimulation site. Thus, the fading of consciousness during certain stages of sleep may be related to a breakdown in cortical effective connectivity.}, Author = {Massimini, Marcello and Ferrarelli, Fabio and Huber, Reto and Esser, Steve K. and Singh, Harpreet and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Wakefulness;Electric Stimulation;Evoked Potentials;Humans;Magnetics;Consciousness;research support, non-u.s. gov't;Male;Sleep;Computer Simulation;Software;Cerebral Cortex;21 Neurophysiology;Adult;24 Pubmed search results 2008;Electroencephalography;Models, Neurological;Brain Mapping}, Month = {9}, Nlm_Id = {0404511}, Number = {5744}, Organization = {Department of Psychiatry, University of Wisconsin, Madison, 6001 Research Park Boulevard, Madison, WI 53719, USA.}, Pages = {2228-32}, Pii = {309/5744/2228}, Pubmed = {16195466}, Title = {Breakdown of cortical effective connectivity during sleep}, Uuid = {2B2CCC4C-8359-4BA8-8442-BA38C39E2A38}, Volume = {309}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1117256}} @article{Masuda-Nakagawa:1994, Abstract = {The principal aim of the present experiments has been to analyze the properties of microglial cells and their role in nerve regeneration. In the leech, damage to the CNS has been shown to be followed by accumulation of laminin and microglial cells at the site of injury (Masuda-Nakagawa et al., 1990. Proc. R. Soc. Lond. B. 241:201-206; and 1993. Proc. Natl. Acad. Sci. USA 90:4966-4970). Procedures were devised for isolating these small, wandering cells from the CNS of the leech. In culture, they were reliably identified by their sizes, shapes, and phagocytotic activity. Their morphology, motility, and interactions with neurons were influenced by the substrate molecules on which they were plated. On the plant lectin concanavalin A (Con A) microglia had a rounded shape and remained stationary. By contrast on extracts of leech extracellular matrix (ECM) enriched with laminin the cells were mobile and spindle-shaped with long processes. On Con A, neuronal growth cones avoided microglial cells, whereas on ECM extract the presence of a microglial cell did not influence neurite growth. Microglial cells showed immunoreactivity on both substrates when stained with a monoclonal antibody against leech laminin. Together these results suggest that microglial cells are influenced in their properties by molecules in the environment and that they could contribute to neuronal outgrowth at the site of an injury.}, Author = {Masuda-Nakagawa, L. M. and Walz, A. and Brodbeck, D. and Neely, M. D. and Grumbacher-Reinert, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Microscopy, Electron, Scanning;Phagocytosis;Animals;Cells, Cultured;Microglia;Axons;Neurites;Leeches;Not relevant;11 Glia;Laminin;Concanavalin A;Extracellular Matrix;Support, Non-U.S. Gov't;Antibodies, Monoclonal;Neurons;Freeze Drying;24 Pubmed search results 2008;Immunohistochemistry;Culture Media;Research Support, Non-U.S. Gov't}, Medline = {94157532}, Month = {1}, Nlm_Id = {0213640}, Number = {1}, Organization = {Department of Pharmacology, Universit{\"a}t Basel, Switzerland.}, Pages = {83-91}, Pubmed = {8113785}, Title = {Substrate-dependent interactions of leech microglial cells and neurons in culture}, Uuid = {B3F0B75C-A48A-4C51-9AD4-6A2CAD78E05A}, Volume = {25}, Year = {1994}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.480250108}} @article{Mataga:2004, Abstract = {Sensory experience physically rewires the brain in early postnatal life through unknown processes. Here, we identify a robust anatomical consequence of monocular deprivation (MD) in layer II/III of visual cortex that corresponds to the rapid, functional loss of responsiveness preceding any changes in axonal input. Protrusions on pyramidal cell apical dendrites increased steadily after eye opening, but were transiently lost through competitive mechanisms after brief MD only during the physiological critical period. Proteolysis by tissue-type plasminogen activator (tPA) conversely declined with age and increased with MD only in young mice. Targeted disruption of tPA release or its upstream regulation by glutamic acid decarboxylase (GAD65) prevented MD-induced spine loss that was pharmacologically rescued concomitant with critical period plasticity. An extracellular mechanism for structural remodeling that is limited to the binocular zone upon proper detection of competing inputs thus links early sensory experience to visual function.}, Author = {Mataga, Nobuko and Mizuguchi, Yoko and Hensch, Takao K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:27 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Visual Cortex;Sensory Deprivation;24 Pubmed search results 2008;research support, non-u.s. gov't;Mice, Knockout;21 Neurophysiology;Glutamate Decarboxylase;Tissue Plasminogen Activator;Dendritic Spines;comparative study;Animals;Humans;Isoenzymes;Mice;Vision, Monocular}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Laboratory for Neuronal Circuit Development, Institute of Physical and Chemical Research (RIKEN), Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.}, Pages = {1031-41}, Pii = {S089662730400755X}, Pubmed = {15603745}, Title = {Experience-dependent pruning of dendritic spines in visual cortex by tissue plasminogen activator}, Uuid = {05CDE761-EA3B-49FD-9CA7-B2C75156F9B4}, Volume = {44}, Year = {2004}, url = {papers/Mataga_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.11.028}} @article{Mato:1996, Abstract = {The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system.}, Author = {Mato, M. and Ookawara, S. and Sakamoto, A. and Aikawa, E. and Ogawa, T. and Mitsuhashi, U. and Masuzawa, T. and Suzuki, H. and Honda, M. and Yazaki, Y. and Watanabe, E. and Luoma, J. and Yla-Herttuala, S. and Fraser, I. and Gordon, S. and Kodama, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Human;Ferritin;Animals;Biological Transport, Active;In Vitro;Macrophages;Aging;Rats;Receptors, Cell Surface;Microglia;Rats, Wistar;Not relevant;Vitamin E Deficiency;Lipoproteins, LDL;Blood-Brain Barrier;Aged;11 Glia;Arterioles;Male;Cerebral Cortex;Horseradish Peroxidase;Adult;Mice;Immunohistochemistry;Microscopy, Electron;Dietary Fats}, Medline = {96194956}, Month = {4}, Nlm_Id = {7505876}, Number = {8}, Organization = {Department of Anatomy, Jichi Medical School, Tochigi, Japan.}, Pages = {3269-74}, Pubmed = {8622926}, Title = {Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex}, Uuid = {6888F5A0-E029-49F3-B833-669E78A95FB1}, Volume = {93}, Year = {1996}} @article{Matsuda:2008, Abstract = {Microglia are believed to play an important role in the regulation of phagocytosis, neuronal survival, neuronal cell death, and inflammation. Recent studies have demonstrated that microglia are multipotential stem cells that give rise to neurons, astrocytes, and oligodendrocytes. However, the functional properties of neurons derived from microglia are poorly understood. In this study, we investigated the possibility that microglia differentiate into functional neurons. Immunocytochemical study demonstrated that microtubule-associated protein 2 (MAP2)-positive cells were derived from microglia under differentiation conditions. Intracellular Ca(2+) imaging study demonstrated that KCl caused no significant changes in [Ca(2+)](i) in microglia, whereas it caused a remarkable increase in [Ca(2+)](i) in microglia-derived cells. Furthermore, electrophysiological study demonstrated that the spike waveform, firing rate, and tetrodotoxin sensitivity of extracellular action potentials evoked by 4-aminopyridine from microglia-derived MAP2-positive cells were nearly identical to those from cultured cortical neurons. These results suggest that microglia-derived MAP2-positive cells possess properties of functional neurons.}, Author = {Matsuda, and Niidome, and Nonaka, and Goto, and Fujimura, and Kato, and Nakanishi, and Akaike, and Kihara, and Sugimoto,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1090-2104}, Journal = {Biochem Biophys Res Commun}, Keywords = {01 Adult neurogenesis general;10 Development;08 Aberrant cell cycle;11 Glia;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0372516}, Organization = {Department of Neuroscience for Drug Discovery, Graduate School of Pharmaceutical Sciences, Kyoto University, Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.}, Pii = {S0006-291X(08)00270-2}, Pubmed = {18284917}, Title = {Microtubule-associated protein 2-positive cells derived from microglia possess properties of functional neurons}, Uuid = {121A8EEF-A3DC-4ABE-990C-830DA8BEABE8}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.bbrc.2008.02.038}} @article{Matsuda:2007, Abstract = {In vivo electroporation is a powerful technique for the introduction of genes into organisms. Temporal and spatial regulation of expression of introduced genes, or of RNAi, would further enhance the utility of this method. Here we demonstrate conditional regulation of gene expression from electroporated plasmids in the postnatal rat retina and the embryonic mouse brain. For temporal regulation, Cre/loxP-mediated inducible expression vectors were used in combination with a vector expressing a conditionally active form of Cre recombinase, which is activated by 4-hydroxytamoxifen. Onset of gene expression was regulated by the timing of 4-hydroxytamoxifen administration. For spatial regulation, transgenes were expressed by using promoters specific for rod photoreceptors, bipolar cells, amacrine cells, M{\"u}ller glia or progenitor cells. Combinations of these constructs will facilitate a variety of experiments, including cell-type-specific gene misexpression, conditional RNAi, and fate mapping of progenitor and precursor cells.}, Author = {Matsuda, Takahiko and Cepko, Constance L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {7505876}, Number = {3}, Organization = {Department of Genetics and Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.}, Pages = {1027-32}, Pii = {0610155104}, Pubmed = {17209010}, Title = {Controlled expression of transgenes introduced by in vivo electroporation}, Uuid = {CCB8B11B-E842-429E-868F-D312B7143B35}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0610155104}} @article{Matsugami:2006, Abstract = {Previous in vitro studies have shown that the neurotransmitter glutamate is important in brain development. Paradoxically, loss-of-function mouse models of glutamatergic signaling that are generated by genetic deletion of glutamate receptors or glutamate release show normal brain assembly. We examined the direct consequences on brain development of extracellular glutamate buildup due to the depletion of the glutamate transporters GLAST and GLT1. GLAST/GLT1 double knockout mice show multiple brain defects, including cortical, hippocampal, and olfactory bulb disorganization with perinatal mortality. Here, we report abnormal formation of the neocortex in GLAST/GLT1 mutants. Several essential aspects of neuronal development, such as stem cell proliferation, radial migration, neuronal differentiation, and survival of SP neurons, were impaired. These results provide direct in vivo evidence that GLAST and GLT1 are necessary for brain development through regulation of extracellular glutamate concentration and show that an important mechanism is likely to be maintenance of glutamate-mediated synaptic transmission.}, Author = {Matsugami, Toshiko R. and Tanemura, Kentaro and Mieda, Michihiro and Nakatomi, Reiko and Yamada, Keiko and Kondo, Takashi and Ogawa, Masaharu and Obata, Kunihiko and Watanabe, Masahiko and Hashikawa, Tsutomu and Tanaka, Kohichi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Neurons;Excitatory Amino Acid Transporter 1;Mutation;Dendrites;Mice, Knockout;24 Pubmed search results 2008;Heterozygote;Gene Deletion;research support, non-u.s. gov't ;Excitatory Amino Acid Transporter 2;Mice, Transgenic;Animals;Brain;Cerebral Cortex;Glutamic Acid;Mice}, Month = {8}, Nlm_Id = {7505876}, Number = {32}, Organization = {Laboratory of Molecular Neuroscience, School of Biomedical Science and Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.}, Pages = {12161-6}, Pii = {0509144103}, Pubmed = {16880397}, Title = {From the Cover: Indispensability of the glutamate transporters GLAST and GLT1 to brain development}, Uuid = {56869094-BB45-4CEE-8146-0F1F9973CC81}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0509144103}} @article{Matsumoto:2007, Abstract = {There is increasing evidence that heparan sulfate (HS) plays an essential role in various axon guidance processes. These observations, however, have not addressed whether HS is required cell autonomously as an axonal coreceptor or as an environmental factor that modulates the localization of guidance molecules in the terrain in which growing axons navigate. Here we demonstrate that netrin-1-mediated commissural axon guidance requires cell-autonomous expression of HS in commissural neurons in vivo. We used the Wnt1-Cre transgene to drive region-specific ablation of Ext1, which encodes an enzyme essential for HS synthesis, in the dorsal part of the spinal cord. Remarkably, Wnt1-Cre-mediated ablation of Ext1 causes commissural axon pathfinding defects that share similarities with those of Netrin-1-deficient and DCC (deleted in colorectal cancer)-deficient mice. Neither Ext1-deficient dorsal spinal cord explants nor wild-type explants in which HS expression was ablated could extend axons in response to netrin-1. Intracellular signaling downstream of netrin-1 and DCC was defective in Ext1-deficient commissural neurons and in DCC-transfected HEK293T cells from which HS was removed. These results demonstrate that the expression of HS by commissural neurons is essential for these neurons to transduce netrin-1 signals, thus providing evidence for a cell-autonomous role of HS in netrin-1/DCC-mediated axon guidance.}, Author = {Matsumoto, Yoshihiro and Irie, Fumitoshi and Inatani, Masaru and Tessier-Lavigne, Marc and Yamaguchi, Yu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {16}, Organization = {Developmental Neurobiology Program, Burnham Institute for Medical Research, La Jolla, California 92037, USA.}, Pages = {4342-50}, Pii = {27/16/4342}, Pubmed = {17442818}, Title = {Netrin-1/DCC signaling in commissural axon guidance requires cell-autonomous expression of heparan sulfate}, Uuid = {BCBF83D2-223A-4D71-8C87-5C20320F8347}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0700-07.2007}} @article{Matsumura:2001, Abstract = {Phosphorylation of regulatory light chain (RMLC) of myosin II at Ser19/Thr18 is likely to play important roles in controlling the morphological changes seen during cell division of cultured mammalian cells. Phosphorylation of RMLC regulates the activity of myosin II, an essntial motor for cytokinesis, and phosphorylation of RMLC shows dramatic changes during mitosis. Two exzymes, myosin phosphatase and kinase, control phosphorvlation of RMLC. Myosin phosphatase is activated during mitosis, apparently as a result of mitosis-specific phosphorylation of the myosin phosphatase targeting subunit (MYPT). This activation of myosin phosphatase is likely to result in RMLC dephosphorylation, causing the disassemly of stress fibers and focal adhesions during prophase. The phosphorylation of MYPT is lost in cyotokinesis, which would decrease myosin phosphatase activity. At the same time, ROCK (Rho-kinase) probably phosphorylates MYPT at its inhibitory sites, further decreasing the activity of myosin phosphatase. These changes in MYPT phosphorylation would raise RMLC phosphorylation, leading to the activation of myosin II for cyotokinesis. RMLC phosphorylation is also regulated by several RMLC kinases including ROCK (Rho-kinase), MLCK and citron kinase, all of which are localized at cleavage furrows. Future studies should examine whether these multiple kinases are redundant or whether they control distinct aspects of cell division. 21939132 0386-7196 Journal Article Review Review, Tutorial}, Author = {Matsumura, F. and Totsukawa, G. and Yamakita, Y. and Yamashiro, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {Cell Struct Funct}, Keywords = {Immunohistochemistry;Myosin-Light-Chain Kinase/metabolism;CK;Phosphoprotein Phosphatase/metabolism;Myosin Light Chains/*metabolism;Animal;Cell Division/*physiology;Phosphorylation;05 Citron Kinase flathead;Protein-Serine-Threonine Kinases/metabolism}, Number = {6}, Organization = {Department of Molecular Biology &Biochemistry, Rutgers University, Piscataway, NJ 08855, USA. matsumura\@mbcl.rutgers.edu}, Pages = {639-44}, Title = {Role of myosin light chain phosphorylation in the regulation of cytokinesis}, Uuid = {BF2B1080-1977-4F01-A3F8-A59ADD6A763F}, Volume = {26}, Year = {2001}, url = {papers/Matsumura_CellStructFunct2001.pdf}} @article{Matthaei:2007, Abstract = {Although genetic manipulations in mice have provided a powerful tool for investigating gene function in vivo, recent studies have uncovered a number of developmental phenomena that complicate the attribution of phenotype to the specific genetic change. A more realistic approach has been to modulate gene expression and function in a temporal and tissue-specific manner. The most common of these methods, the CreLoxP and tetracycline response systems, are surveyed here and their recently identified shortcomings discussed, along with a less well known system based on the E. coli lac operon and modified for use in mammals. The potential for further complications in interpretation due to hitherto unexpected epigenetic effects involving transfer of RNA or protein in oocytes or sperm is also explored. Given these problems we reiterate the necessity for the use of completely reversible methods that will allow each experimental group of animals to act as their own control. Using these methods with a number of specific modifications to eliminate non-specific effects from random insertion sites and inducer molecules, the full potential of genetic manipulation studies should be realized.}, Author = {Matthaei, Klaus I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Tissue Distribution;Animals;Trans-Activators;Aging;Tetracycline;review;Embryo, Mammalian;Integrases;Mice, Transgenic;Gene Deletion;Protein Synthesis Inhibitors;Animals, Newborn;Genetic Engineering;Epigenesis, Genetic;Escherichia coli;Lac Operon;Mice;24 Pubmed search results 2008;Gene Expression;Transgenes}, Month = {7}, Nlm_Id = {0266262}, Number = {Pt 2}, Organization = {Gene Targeting Laboratory, The John Curtin School of Medical Research, GPO Box 334, Canberra City, ACT 0200, Australia. klaus.matthaei\@anu.edu.au}, Pages = {481-8}, Pii = {jphysiol.2007.134908}, Pmc = {PMC2075346}, Pubmed = {17495035}, Title = {Genetically manipulated mice: a powerful tool with unsuspected caveats}, Uuid = {18D8B6EF-4F03-4B09-AD4B-440FD0913D0A}, Volume = {582}, Year = {2007}, url = {papers/Matthaei_JPhysiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2007.134908}} @article{Mattia:1995, Abstract = {Application of the convulsant drug 4-aminopyridine (50 to 100 microM) induced spontaneous seizure-like discharges (duration = 76.3 +/- 46.8 sec, mean +/- SD; interval of occurrence = 225.2 +/- 87.9 sec) in slices of neocortex obtained from patients with a diagnosis of focal neuronal migration disorders during neurosurgical procedures for relief of drug-resistant seizures. Similar epileptiform discharges could also be elicited in these slices by single-shock stimuli delivered in the underlying white matter or within the gray matter. By contrast, neocortical slices obtained from patients suffering from temporal lobe epilepsy (which is characterized by Ammon's horn sclerosis but relatively normal neocortex) did not generate any epileptiform activity during 4-aminopyridine application. Thus, our study is the first to provide experimental evidence for the intrinsic epileptogenicity that characterizes neuronal migration disorders.}, Author = {Mattia, D. and Olivier, A. and Avoli, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {Epilepsies, Partial;Research Support, Non-U.S. Gov't;21 Neurophysiology;4-Aminopyridine;Action Potentials;Cells, Cultured;Humans;Cerebral Cortex;24 Pubmed search results 2008;21 Epilepsy}, Medline = {95342419}, Month = {7}, Nlm_Id = {0401060}, Number = {7}, Organization = {Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, PQ, Canada.}, Pages = {1391-5}, Pubmed = {7617202}, Title = {Seizure-like discharges recorded in human dysplastic neocortex maintained in vitro}, Uuid = {15AAED9A-9C4A-46E2-8FD3-B26561EBF651}, Volume = {45}, Year = {1995}} @article{Mattson:2004, Author = {Mattson, Mark P. and Taub, Dennis D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {15 ERVs retroelements;Pregnancy Proteins;Endogenous Retroviruses;Multiple Sclerosis;Cytokines;Encephalitis;Gene Products, env;Astrocytes;Reactive Oxygen Species;11 Glia;comment;15 Retrovirus mechanism;Humans;24 Pubmed search results 2008;Oxidative Stress;news}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Pages = {1021-3}, Pii = {nn1004-1021}, Pubmed = {15452568}, Title = {Ancient viral protein enrages astrocytes in multiple sclerosis}, Uuid = {E410D850-3650-4B2B-B169-10EFFF15EF48}, Volume = {7}, Year = {2004}, url = {papers/Mattson_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1004-1021}} @article{Mattsson:1997, Abstract = {BACKGROUND AND PURPOSE: The purpose of this study was to evaluate whether grafting of fetal neocortical tissue 1 week after focal brain ischemia improved behavioral outcome and reduced secondary thalamic atrophy. METHODS: One week after distal ligation of the right middle cerebral artery in spontaneously hypertensive male rats, blocks of fetal neocortex (embryonic day 17) were homografted to rats housed in standard or enriched environments. Control infarcted nongrafted rats were housed in the enriched environment. Behavioral outcome was repeatedly tested until the rats were killed 20 weeks after the ligation. Ten days earlier, a mixture of 2\%Fluoro-Gold and 10\%biotinylated dextran amine was injected into the transplants for retrograde and anterograde tracing of graft-host connections. RESULTS: Grafted and nongrafted rats with enriched housing performed significantly better than grafted rats with standard housing on a rotating pole and a prehensile traction test. Grafted "enriched"rats were moreover significantly better than grafted "standard"rats and nongrafted enriched rats in a rotation test and a postural and locomotor tail position test. In the latter test, nongrafted enriched rats performed significantly better than grafted standard rats. The lesion-induced atrophy in posterior thalamus with its major sensorimotor cortex relay nuclei was significantly reduced in grafted enriched rats compared with nongrafted enriched rats. Afferent and efferent graft-host connections were identified in both grafted groups. Graft volumes did not differ. CONCLUSIONS: Neural grafting enhanced functional outcome and reduced thalamic atrophy only when combined with housing in enriched environments. 0039-2499 Journal Article}, Author = {Mattsson, B. and Sorensen, J. C. and Zimmer, J. and Johansson, B. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Stroke}, Keywords = {Fetus;17 Transplant Regeneration;Rats;L abstr;Housing, Animal;Cerebral Infarction/pathology/*physiopathology/*surgery;*Environment;Atrophy;Rats, Inbred SHR;Thalamus/*pathology;Animals;Support, Non-U.S. Gov't;Male;Cerebral Cortex/*transplantation;*Behavior, Animal}, Number = {6}, Organization = {Laboratory for Experimental Neurology, Wallenberg Neuroscience Center, Lund University Hospital, Sweden.}, Pages = {1225-31; discussion 1231-2}, Pubmed = {9183356}, Title = {Neural grafting to experimental neocortical infarcts improves behavioral outcome and reduces thalamic atrophy in rats housed in enriched but not in standard environments}, Uuid = {873928BF-EC80-11DA-8605-000D9346EC2A}, Volume = {28}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9183356}} @article{Matute-Bello:2004, Abstract = {To determine the time required to repopulate mouse lungs with donor alveolar macrophages following total body irradiation (TBI) and bone marrow transplantation (BMT), C57Bl/6 mice were subjected to TBI with 900 cGy, followed by transplantation of bone marrow cells from mice expressing green fluorescent protein (GFP) in their somatic cells. The mice were euthanized at either 30 (n=5), 60 (n=5) or 90 (n=5) days following BMT. Thirty days following transplantation, 87.8 +/- 3.9\%(mean +/- S.E.M.) circulating leukocytes in recipient mice were derived from the donor, as determined by fluorescence activated cell sorting (FACS) analysis for GFP. However, only 46.9 +/- 7.4\%of the resident alveolar cells expressed GFP, indicating incomplete repopulation. By day 60 post-transplantation, the percentage of bronchoalveolar lavage fluid (BALF) cells expressing GFP reached 74.5 +/- 2.4\%, remaining stable 90 days after transplantation (80.4 +/- 1.9\%). We conclude that 60 days after TBI with 900 cGy and bone marrow transplantation, the majority of the lung resident alveolar macrophages is of donor origin. This study provides useful information regarding the time of reconstitution with donor alveolar macrophages in the pulmonary airspaces of recipient mice following marrow transplantation.}, Author = {Matute-Bello, Gustavo and Lee, Janet S. and Frevert, Charles W. and Liles, W. Conrad and Sutlief, Steven and Ballman, Kimberly and Wong, Venus and Selk, Amy and Martin, Thomas R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0022-1759}, Journal = {J Immunol Methods}, Keywords = {Macrophages, Alveolar;Adoptive Transfer;Luminescent Proteins;Research Support, U.S. Gov't, P.H.S.;Time Factors;Mice, Inbred C57BL;Bone Marrow Transplantation;11 Glia;Whole-Body Irradiation;Animals;Mice;Green Fluorescent Proteins}, Month = {9}, Nlm_Id = {1305440}, Number = {1-2}, Organization = {Pulmonary and Critical Care Division, Department of Medicine, University of Washington, Seattle, WA 98108, USA.}, Pages = {25-34}, Pii = {S0022-1759(04)00203-0}, Pubmed = {15350509}, Title = {Optimal timing to repopulation of resident alveolar macrophages with donor cells following total body irradiation and bone marrow transplantation in mice}, Uuid = {2A23F70E-F4D1-4AA9-A8A7-50944B37C2EB}, Volume = {292}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jim.2004.05.010}} @article{Mautes:2000, Abstract = {Oxidative stress contributes to secondary injury after spinal cord trauma. Among the consequences of oxidative stress is the induction of heme oxygenase-1 (HO-1), an inducible isozyme that metabolizes heme to iron, biliverdin, and carbon monoxide. Here we examine the induction of HO-1 in the hemisected spinal cord, a model that results in reproducible degeneration in the ipsilateral white matter. HO-1 was induced in microglia and macrophages from 24 h to at least 42 days after injury. Within the first week after injury, HO-1 was induced in both the gray and the white matter. Thereafter, HO-1 expression was limited to degenerating fiber tracts. HSP70, a heat shock protein induced mainly by the presence of denatured proteins, was consistently colocalized with HO-1 in the microglia and macrophages. This study to demonstrates long-term induction of HO-1 and HSP70 in microglia and macrophages after traumatic injury and an association between induction of HO-1 and Wallerian degeneration. White matter degeneration is characterized by phagocytosis of cellular debris and remodeling of surviving tissue. This results in the metabolism, synthesis, and turnover of heme and heme proteins. Thus, sustained induction of HO-1 and HSP70 in microglia and macrophages suggests that tissue degeneration is an ongoing process, lasting 6 weeks and perhaps even longer.}, Author = {Mautes, A. E. and Bergeron, M. and Sharp, F. R. and Panter, S. S. and Weinzierl, M. and Guenther, K. and Noble, L. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Animals;Astrocytes;Myelitis;Macrophages;Rats;Anterior Horn Cells;Heat-Shock Proteins 70;Microglia;Axons;Rats, Sprague-Dawley;Not relevant;11 Glia;Male;Spinal Cord Injuries;Oxidative Stress;Heme Oxygenase (Decyclizing);Support, Non-U.S. Gov't;Wallerian Degeneration;Support, U.S. Gov't, P.H.S.}, Medline = {20539894}, Month = {12}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Neurosurgery, University of California at San Francisco, San Francisco, California, 94143, USA.}, Pages = {254-65}, Pii = {S0014488600975204}, Pubmed = {11085891}, Title = {Sustained induction of heme oxygenase-1 in the traumatized spinal cord}, Uuid = {FF8E1D55-98AC-4E0D-A4C0-4AE4C1FE916B}, Volume = {166}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.2000.7520}} @article{Mayne:2003, Abstract = {Due to their phagocytic and poorly proliferative nature, it has been difficult to transfect human monocytes and macrophages. Adenoviral vectors have recently allowed transduction of a high percentage of human macrophages, but only after CSF upregulation of the integrins, alphavbeta3 or alphavbeta5, during culture for 48 h, a time allowing significant monocyte to macrophage differentiation. In our hands, after 24-h incubation with M-CSF (20 ng/ml) and a further 24-h incubation with an adenoviral vector encoding green fluorescent protein (AdV-GFP) [multiplicity of infection (MOI)=50:1], only 35\%of CD14-positive cells express GFP. We report that centrifugation of these cells with AdV-GFP at 2000 x g for 1 h at 37 degrees C significantly enhanced the number of cells expressing GFP (to 65\%) and the level of GFP expression per transduced cell (fivefold). The viability of the cells was not compromised (<5 \%CD14-positive cells were 7-aminoactinomycin D (7AAD)-positive after 24 h AdV-GFP exposure at MOI=50:1). Centrifugation allowed efficient transduction of monocytes and macrophages with an MOI at least tenfold lower than otherwise required and did not activate the transduced cells or affect their ability to produce TNFalpha or IL-1beta in response to lipopolysaccharide (LPS). This methodology was also suitable for transducing large numbers of in vitro monocyte-derived macrophages (MDMac) and macrophages isolated from synovial fluids with up to 75-80\%of CD14-positive cells transduced after 24-h exposure to AdV-GFP (50:1) and centrifugation (2000 x g). This methodology should provide significant expression of transgenes in human monocytes and macrophages.}, Author = {Mayne, George C. and Borowicz, Romana A. and Greeneklee, Kate V. L. and Finlay-Jones, John J. and Williams, Keryn A. and Hart, Prue H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0022-1759}, Journal = {J Immunol Methods}, Keywords = {Cell Survival;Transduction, Genetic;Animals;Monocytes;Macrophages;Humans;Integrins;Tumor Necrosis Factor-alpha;Receptors, Vitronectin;Extracellular Space;11 Glia;Green Fluorescent Proteins;Centrifugation;Genetic Vectors;Integrin alphaVbeta3;Interleukin-1;Flow Cytometry;Adenoviridae;Luminescent Proteins;Synovial Fluid;Research Support, Non-U.S. Gov't}, Medline = {22838810}, Month = {7}, Nlm_Id = {1305440}, Number = {1-2}, Organization = {Department of Microbiology and Infectious Diseases, School of Medicine, Flinders University, GPO Box 2100, Adelaide 5001, Australia.}, Pages = {45-56}, Pii = {S0022175903002291}, Pubmed = {12957395}, Title = {Centrifugation facilitates transduction of green fluorescent protein in human monocytes and macrophages by adenovirus at low multiplicity of infection}, Uuid = {B96728CB-A2B5-47AE-9883-32D31887F444}, Volume = {278}, Year = {2003}} @article{Maysinger:1996, Abstract = {The aim of this study was to develop delivery systems for administration of CSF-1 to remedy the systemic deficiency of this cytokine in osteopetrotic op/op mice and to study the microglial response and neuronal survival in op/op mice following cerebral cortex ischemic lesion. Unilateral cerebral cortex ischemic lesions were produced in homozygous op/op mice and either microencapsulated rhCSF-1 or LM-10 fibroblast-like cells producing CSF-1 were administered either locally, at the site and time of the lesioning, or into the peritoneum 2 weeks before the lesion was made. Physical properties (shape, size, integrity) and kinetics of rhCSF-1 release were assessed prior to the experiments in situ. Depending on the characteristics of the biodegradable polymer (e.g., chitosan with different densities or poly-L-lactic-poly-glycolic acid), remarkable differences in survival of encapsulated cells were observed. Cellular integrity following encapsulation and metabolic activity was regularly assessed for a period of 1 month. The best level of viability was achieved with highly viscous chitosan (311). The results from these studies demonstrate that: (1) rhCSF-1 incorporated into biodegradable spheres can be released and retain its biological activity; (2) microencapsulated LM-10 cells which produce CSF-1 can survive and constitutively release CSF-1 in alginate-chitosan spheres for different lengths of time depending on the physical properties of the chitosan used; and (3) CSF-1 is an important growth factor in the central nervous system where it can both strongly alter morphological changes of microglia and enhance survival of neurons in injured brain.}, Author = {Maysinger, D. and Berezovskaya, O. and Fedoroff, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cell Survival;Human;Animals;Capsules;Osteopetrosis;Mice, Mutant Strains;Recombinant Proteins;Fibroblasts;Brain;Cell Count;11 Glia;Nerve Growth Factors;Cell Line;Biopolymers;Microspheres;Support, Non-U.S. Gov't;Macrophage Colony-Stimulating Factor;Mice;Drug Delivery Systems;Microscopy, Electron}, Medline = {96390694}, Month = {9}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.}, Pages = {47-56}, Pii = {S0014488696901387}, Pubmed = {8797667}, Title = {The hematopoietic cytokine colony stimulating factor 1 is also a growth factor in the CNS: (II). Microencapsulated CSF-1 and LM-10 cells as delivery systems}, Uuid = {52E5AB29-6EE8-4DF7-A34A-E25E63F0E0C4}, Volume = {141}, Year = {1996}} @article{Mazzoni:1994, Abstract = {The presence and binding properties of epidermal growth-factor receptors (EGF-Rs) in different cell types purified from the rat medial septal area in culture were investigated. We report that astrocytes, oligodendrocytes and neurons from this area possess EGF-Rs while microglia do not. EGF-binding sites are detectable on astrocytes derived from the medial septum of both embryonic and neonatal rats. Scatchard analysis of the data for astrocytes from the fetal rats show that EGF specifically binds to both high- (Kd = 7.21 x 10(-10) M, Bmax = 3602 receptors/cell) and low-affinity (Kd = 3.99 x 10(-8) M, Bmax = 86,265 receptors/cell) receptors on these cells. On the other hand, astrocytes purified from neonatal tissue possess a greater number of high-affinity receptors (Bmax = 10,938 receptors/cell) when compared with the embryonic astroglia. With time in culture, the number of both types of receptors on neonatal astrocytes decreases. Oligodendrocytes also possess high- and low-affinity EGF-Rs with dissociation constants of 3.25 x 10(-10) M and 3.85 x 10(-8) M, respectively. The number of receptors on oligodendrocytes is significantly lower than those of neonatal astrocytes (Bmax = 1185 and 25,081 receptors/cell for high- and low-affinity binding sites, respectively). Finally, neurons from this area also exhibit two different EGF-R types with dissociation constants similar to those described for astrocytes. As the number of receptors/neuron (Bmax = 136 and 1159 receptors/cell for high- and low-affinity binding sites, respectively) appears to be extremely low, it is possible that EGF specifically binds only to a subpopulation of neurons from this area. These studies demonstrate which cell types in the developing medial septal area possess EGF-Rs and provide a detailed characterization of these binding sites. These EGF-R-bearing cells may be potential targets for this growth factor or for transforming growth factor alpha in this brain area.}, Author = {Mazzoni, I. E. and Kenigsberg, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Animals;Receptor, Epidermal Growth Factor;Astrocytes;Cells, Cultured;Rats;Microglia;Oligodendroglia;Iodine Radioisotopes;Rats, Sprague-Dawley;Kinetics;11 Glia;Septal Nuclei;Alpha;Neuroglia;Epidermal Growth Factor;Neurons;Isotope Labeling;Immunohistochemistry;Lectins;Research Support, Non-U.S. Gov't}, Medline = {95103258}, Month = {9}, Nlm_Id = {0045503}, Number = {1}, Organization = {Department of Physiology, University of Montreal, Que., Canada.}, Pages = {115-26}, Pubmed = {7804824}, Title = {Localization and characterization of epidermal growth-factor receptors in the developing rat medial septal area in culture}, Uuid = {4DD506E9-6CE1-45F1-A385-5C56A25C36E8}, Volume = {656}, Year = {1994}} @article{Mazzoni:2007, Abstract = {Most neuronal networks, even in the absence of external stimuli, produce spontaneous bursts of spikes separated by periods of reduced activity. The origin and functional role of these neuronal events are still unclear. The present work shows that the spontaneous activity of two very different networks, intact leech ganglia and dissociated cultures of rat hippocampal neurons, share several features. Indeed, in both networks: i) the inter-spike intervals distribution of the spontaneous firing of single neurons is either regular or periodic or bursting, with the fraction of bursting neurons depending on the network activity; ii) bursts of spontaneous spikes have the same broad distributions of size and duration; iii) the degree of correlated activity increases with the bin width, and the power spectrum of the network firing rate has a 1/f behavior at low frequencies, indicating the existence of long-range temporal correlations; iv) the activity of excitatory synaptic pathways mediated by NMDA receptors is necessary for the onset of the long-range correlations and for the presence of large bursts; v) blockage of inhibitory synaptic pathways mediated by GABA(A) receptors causes instead an increase in the correlation among neurons and leads to a burst distribution composed only of very small and very large bursts. These results suggest that the spontaneous electrical activity in neuronal networks with different architectures and functions can have very similar properties and common dynamics.}, Author = {Mazzoni, Alberto and Broccard, Fr{\'e}d{\'e}ric D. and Garcia-Perez, Elizabeth and Bonifazi, Paolo and Ruaro, Maria Elisabetta and Torre, Vincent}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 03:01:15 +0000}, Issn = {1932-6203}, Journal = {PLoS ONE}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008; currOpinRvw}, Nlm_Id = {101285081}, Organization = {International School for Advanced Studies, Trieste, Italy.}, Pages = {e439}, Pubmed = {17502919}, Title = {On the dynamics of the spontaneous activity in neuronal networks}, Uuid = {33E677EC-FD72-4D6A-96FC-58372CBDF09A}, Volume = {2}, Year = {2007}, url = {papers/Mazzoni_PLoSONE2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0000439}} @article{Maurer:2003, Abstract = {Macrophages have recently been shown to be critically involved in the pathogenesis of genetically determined demyelination in mice heterozygously deficient for P0 (P0(+-)). Since little is known about the origin of these cells, we created chimeric P0(+-) mice by transplanting bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated P0(+-) mice. When analyzing chimeric P0(+-) mice, we could determine two populations (GFP(+) and GFP(-)) of endoneurial macrophages that became phagocytic for myelin and increased in number. We found that both GFP(-) resident macrophages and GFP(+) macrophages proliferated in peripheral nerves of P0(+-) mice but not in nerves of chimeric or nonchimeric P0(++) mice. These findings demonstrate a so far poorly recognized role of resident endoneurial macrophages in demyelinating neuropathies. Surprisingly, we also found GFP(+) cells that unequivocally showed the morphological characteristics of fibroblasts. These blood-borne fibroblast-like cells express the common hematopoetic stem cell marker CD34 and might comprise another cell type of potential importance for immune regulation in hereditary demyelinating neuropathies.}, Author = {M{\"a}urer, Mathias and M{\"u}ller, Marcus and Kobsar, Igor and Leonhard, Christine and Martini, Rudolf and Kiefer, Reinhard}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {Peripheral Nerves;Phagocytosis;Animals;Myelin Sheath;Microscopy, Immunoelectron;Macrophages;Bone Marrow Transplantation;Phenotype;Fibroblasts;Cell Movement;Mice, Transgenic;Mice, Inbred C57BL;Green Fluorescent Proteins;Transplantation Chimera;Disease Models, Animal;11 Glia;Spinal Nerve Roots;Peripheral Nervous System Diseases;Mice;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22722092}, Month = {7}, Nlm_Id = {9100095}, Number = {3}, Organization = {Department of Neurology, Bayerische Julius-Maximilians-Universit{\"a}t W{\"u}rzburg, D-97080 W{\"u}rzburg, Germany.}, Pages = {351-9}, Pii = {S1044743103000551}, Pubmed = {12837620}, Title = {Origin of pathogenic macrophages and endoneurial fibroblast-like cells in an animal model of inherited neuropathy}, Uuid = {46F301AD-28D9-4511-BD13-F1FCA0E1C40E}, Volume = {23}, Year = {2003}} @article{McAllister:1995, Abstract = {Although dendritic growth and differentiation are critical for the proper development and function of neocortex, the molecular signals that regulate these processes are largely unknown. The potential role of neurotrophins was tested by treating slices of developing visual cortex with NGF, BDNF, NT-3, or NT-4 and by subsequently visualizing the dendrites of pyramidal neurons using particle-mediated gene transfer. Specific neurotrophins increased the length and complexity of dendrites of defined cell populations. Basal dendrites of neurons in each cortical layer responded most strongly to a single neurotrophin: neurons in layer 4 to BDNF and neurons in layers 5 and 6 to NT-4. In contrast, apical dendrites responded to a range of neurotrophins. On both apical and basal dendrites, the effects of the TrkB receptor ligands, BDNF and NT-4, were distinct. The spectrum of neurotrophic actions and the laminar specificity of these actions implicate endogenous neurotrophins as regulatory signals in the development of specific dendritic patterns in mammalian neocortex.}, Author = {McAllister, A. K. and Lo, D. C. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Gene Transfer Techniques;Visual Cortex;Nerve Growth Factors;Dendrites;10 Development;10 Structural plasticity;Beta;Nerve Tissue Proteins;Ferrets;Support, U.S. Gov't, P.H.S.;beta-Galactosidase;Brain-Derived Neurotrophic Factor;Organ Culture;Animals;Support, Non-U.S. Gov't;Neurons;Neurotrophin 3}, Medline = {96049128}, Month = {10}, Nlm_Id = {8809320}, Number = {4}, Organization = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.}, Pages = {791-803}, Pubmed = {7576629}, Title = {Neurotrophins regulate dendritic growth in developing visual cortex}, Uuid = {684E3BB2-058F-4040-BE51-4D8ACF29F1DA}, Volume = {15}, Year = {1995}} @article{McBride:1988, Abstract = {We studied Clarke's Column of the L-1 spinal cord segment of young adult female rats after first prelabeling its neurons by the intracerebellar injection of Fluoro-Gold or true blue and subsequently axotomizing the labeled cells by a complete spinal cord transection at T-9. In control rats, the number of labeled neurons at 1, 5, 10, and 20 weeks showed a progressive decrease, probably due to leakage of dye from the cells. A much greater loss of labeled neurons was found in T-9 spinal cord-transected rats than in their matched controls. At 5 weeks after transection, loss of large neurons was somewhat offset by an increase in small neurons; neuron shrinkage was a likely cause of this increase, because small, very intensely labeled neurons were found in transected rats but not in control rats. By 10 and 20 weeks post-transection, the number of all prelabeled neurons in transected rats had sharply decreased. In transected rats, but not in controls, very significant increases in labeled astroglia and microglia and other labeled small cells were found at 5 weeks. At 10 weeks, the identifiable labeled astroglia had decreased but marked increases in microglia and other labeled small cells persisted. We conclude that, following a complete T-9 spinal cord transection, axotomized Clarke's column neurons first shrink in size and then die. Labeled reactive astrocytes, which are most evident 5 weeks after injury, probably indicate phagocytosis of axotomized neurons.}, Author = {McBride, R. L. and Feringa, E. R. and Smith, B. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Female;Rats;Astrocytes;Not relevant;Denervation;Fluorescent Dyes;Cell Survival;Support, U.S. Gov't, Non-P.H.S.;Spinal Cord;Microscopy, Fluorescence;11 Glia;Stilbamidines;Animals;Rats, Inbred Strains;Neurons;Benzofurans}, Medline = {89031111}, Month = {11}, Nlm_Id = {0370712}, Number = {2}, Organization = {V.A. Medical Center, Medical College of Georgia, Augusta 30910.}, Pages = {236-43}, Pubmed = {3181363}, Title = {The fate of prelabeled Clarke's column neurons after axotomy}, Uuid = {47C7F37F-522A-4CBE-85DA-1C96F7A9E51E}, Volume = {102}, Year = {1988}} @article{McBride:2004, Abstract = {The present study investigated the neuroanatomical and behavioral effects of human stem cell transplants into the striatum of quinolinic acid (QA)-lesioned rats. Twenty-four rats received unilateral QA (200 nM/microl) injections into the striatum. One week later, rats were transplanted with stem cells derived from human fetal cortex (12 weeks postconception) that were either 1) pretreated in culture media with the differentiating cytokine ciliary neurotrophic factor (CNTF; n = 9) or 2) allowed to grow in culture media alone (n=7). Each rat was injected with a total of 200,000 cells. A third group of rats (n=8) was given a sham injection of vehicle. Rats transplanted with human stem cells performed significantly better over the 8 weeks of testing on the cylinder test compared with those treated with vehicle (P < or = 0.001). Stereological striatal volume analyses performed on Nissl-stained sections revealed that rats transplanted with CNTF-treated neurospheres had a 22\%greater striatal volume on the lesioned side compared with those receiving transplants of untreated neurospheres (P = 0.0003) and a 26\%greater striatal volume compared with rats injected with vehicle (P < or = 0.0001). Numerous human nuclei-positive cells were visualized in the striatum in both transplantation groups. Grafted cells were also observed in the globus pallidus, entopeduncular nucleus, and substantia nigra pars reticulata, areas of the basal ganglia receiving striatal projections. Some of the human nuclei-positive cells coexpressed glial fibrillary acidic protein and NeuN, suggesting that they had differentiated into neurons and astrocytes. Taken together, these data demonstrate that striatal transplants of human fetal stem cells elicit behavioral and anatomical recovery in a rodent model of Huntington's disease.}, Author = {McBride, Jodi L. and Behrstock, Soshana P. and Chen, Er-Yun Y. and Jakel, Rebekah J. and Siegel, Irwin and Svendsen, Clive N. and Kordower, Jeffrey H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Glial Fibrillary Acidic Protein;Movement;Cell Differentiation;Rats, Inbred Lew;Ciliary Neurotrophic Factor;Astrocytes;Corpus Striatum;Treatment Outcome;Rats;Transplantation, Heterologous;Recovery of Function;Cells, Cultured;Humans;Animals;Stem Cell Transplantation;Disease Models, Animal;Male;Nerve Regeneration;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neurons;Quinolinic Acid;Huntington Disease;24 Pubmed search results 2008;Graft Survival;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {0406041}, Number = {2}, Organization = {Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA.}, Pages = {211-9}, Pubmed = {15211462}, Title = {Human neural stem cell transplants improve motor function in a rat model of Huntington's disease}, Uuid = {B13E991D-9ED7-4351-9243-DDD6C6E83E80}, Volume = {475}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20176}} @article{McCabe:2006, Abstract = {Waves of spontaneous electrical activity that are highly synchronized across large populations of neurones occur throughout the developing mammalian central nervous system. The stages at which this activity occurs are tightly regulated to allow activity-dependent developmental programmes to be initiated correctly. What determines the onset and cessation of spontaneous synchronous activity (SSA) in a particular region of the nervous system, however, remains unclear. We have tested the hypothesis that activity itself triggers developmental changes in intrinsic and circuit properties that determine the stages at which SSA occurs. To do this we exposed cultured slices of mouse neocortex to tetrodotoxin (TTX) to block SSA, which normally occurs between embryonic day 17 (E17) and postnatal day 3 (P3). In control cultured slices, SSA rarely occurs after P3. In TTX-treated slices, however, SSA was generated from P3 (the day of TTX removal) until at least P10. This indicates that in the absence of spontaneous activity, the mechanisms that normally determine the timing of SSA are not initiated, and that a compensatory response occurs that shifts the time of SSA occurrence to later developmental stages.}, Author = {McCabe, Annette K. and Chisholm, Sarah L. and Picken-Bahrey, Heidi L. and Moody, William J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {24 Pubmed search results 2008;Biological Clocks;21 Neurophysiology;Action Potentials;Feedback;Neuronal Plasticity;research support, u.s. gov't, non-p.h.s.;Animals;Mice;Cerebral Cortex;Neurons;21 Cortical oscillations}, Month = {11}, Nlm_Id = {0266262}, Number = {Pt 1}, Organization = {Department of Biology, University of Washington, Seattle, WA 98195, USA.}, Pages = {155-67}, Pii = {jphysiol.2006.117523}, Pubmed = {16945966}, Title = {The self-regulating nature of spontaneous synchronized activity in developing mouse cortical neurones}, Uuid = {A5D07BD2-8ADD-40F6-9F33-1E604BA510D8}, Volume = {577}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2006.117523}} @article{McCaffrey:2002, Abstract = {RNA interference is an evolutionarily conserved surveillance mechanism that responds to double-stranded RNA by sequence-specific silencing of homologous genes. Here we show that transgene expression can be suppressed in adult mice by synthetic small interfering RNAs and by small-hairpin RNAs transcribed in vivo from DNA templates. We also show the therapeutic potential of this technique by demonstrating effective targeting of a sequence from hepatitis C virus by RNA interference in vivo. 0028-0836 Journal Article}, Author = {McCaffrey, A. P. and Meuse, L. and Pham, T. T. and Conklin, D. S. and Hannon, G. J. and Kay, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:53 -0400}, Journal = {Nature}, Keywords = {Hepacivirus/*genetics;Human;Liver/metabolism;Luciferase/biosynthesis/genetics;RNA, Untranslated/chemistry/*genetics/*metabolism;Aging/*genetics;Animals;Recombinant Fusion Proteins/biosynthesis/genetics;Genes, Reporter/genetics;T pdf;23 Technique;RNA, Small Interfering;RNA, Viral/genetics/metabolism;Substrate Specificity;*Gene Silencing;RNA, Double-Stranded/chemistry/genetics/metabolism;Mice;Viral Nonstructural Proteins/biosynthesis/genetics;Transgenes/genetics}, Number = {6893}, Organization = {Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305-5208, USA.}, Pages = {38-9}, Title = {RNA interference in adult mice}, Uuid = {FF057C67-E1CD-4C22-A9E5-7733A5E720BB}, Volume = {418}, Year = {2002}, url = {papers/McCaffrey_Nature2002.pdf}} @article{McCann:2007, Abstract = {To examine the role of retrograde signals on synaptic maintenance, we inhibited protein synthesis in individual postsynaptic cells in vivo while monitoring presynaptic terminals. Within 12 h, axon terminals begin to atrophy and withdraw from normal postsynaptic sites. Structural similarities between this process and naturally occurring synapse elimination suggest that short-lived target derived factors not only participate in synaptic maintenance in adults, but also regulate elimination of connections during development.}, Author = {McCann, Corey M. and Nguyen, Quyen T. and Santo Neto, Humberto and Lichtman, Jeff W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;Synaptic Membranes;Protein Synthesis Inhibitors;Time Factors;Neuromuscular Junction;comparative study;Receptors, Cholinergic;Animals;Mice;24 Pubmed search results 2008;Axons}, Month = {5}, Nlm_Id = {8102140}, Number = {22}, Organization = {Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.}, Pages = {6064-7}, Pii = {27/22/6064}, Pubmed = {17537978}, Title = {Rapid synapse elimination after postsynaptic protein synthesis inhibition in vivo}, Uuid = {CA1DAE14-D09B-414C-9C98-9C7AB545FD05}, Volume = {27}, Year = {2007}, url = {papers/McCann_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0627-07.2007}} @article{McCann:2008, Abstract = {Synaptic plasticity underlies the adaptability of the mammalian brain, but has been difficult to study in living animals. Here we imaged the synapses between pre- and postganglionic neurons in the mouse submandibular ganglion in vivo, focusing on the mechanisms that maintain and regulate neurotransmitter receptor density at postsynaptic sites. Normally, synaptic receptor densities were maintained by rapid exchange of receptors with nonsynaptic regions (over minutes) and by continual turnover of cell surface receptors (over hours). However, after ganglion cell axons were crushed, synaptic receptors showed greater lateral mobility and there was a precipitous decline in insertion. These changes led to near-complete loss of synaptic receptors and synaptic depression. Disappearance of postsynaptic spines and presynaptic terminals followed this acute synaptic depression. Therefore, neurotransmitter receptor dynamism associated with rapid changes in synaptic efficacy precedes long-lasting structural changes in synaptic connectivity.}, Author = {McCann, Corey M. and Tapia, Juan Carlos and Kim, Han and Coggan, Jay S. and Lichtman, Jeff W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {in vitro;Presynaptic Terminals;Animals;Synapses;Gene Expression Regulation;Bungarotoxins;Nonlinear Dynamics;Mice, Transgenic;research support, non-u.s. gov't;Time Factors;Analysis of Variance;Receptors, Cholinergic;Axotomy;Neurons;Intracellular Signaling Peptides and Proteins;Mice;Luminescent Proteins;24 Pubmed search results 2008;Submandibular Gland;Excitatory Postsynaptic Potentials}, Month = {7}, Nlm_Id = {9809671}, Number = {7}, Organization = {Department of Molecular & Cellular Biology, Harvard University, 7 Divinity Ave., Cambridge, Massachusetts 02138, USA.}, Pages = {807-15}, Pii = {nn.2145}, Pubmed = {18568021}, Title = {Rapid and modifiable neurotransmitter receptor dynamics at a neuronal synapse in vivo}, Uuid = {61D33AB0-A02C-43CD-B4AA-4A263CA08664}, Volume = {11}, Year = {2008}, url = {papers/McCann_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2145}} @article{McCann:1996, Abstract = {We have investigated the response of astrocytes and microglia to trimethyl tin intoxication in the septum, hippocampus, olfactory bulb, and pyriform cortex of the rat. Microglia were studied qualitatively using lectin histochemistry, and astrocytes were examined both qualitatively with immunohistochemistry, and quantitatively using an immunoassay for glial fibrillary acidic protein. Our results show that activated microglia first appeared 2 days after trimethyl tin intoxication in the lateral septum and hippocampus. Four days after trimethyl tin intoxication, the same regions revealed a most intense microglial reaction characterized by microglial hypertrophy and the formation of phagocytic clusters. By day 7, microglial activation in the septum and hippocampus had lessened, suggesting that the cells were reverting to the resting phenotype. The microglial response in the pyriform cortex and olfactory bulb, while being later in onset than in the septum and hippocampus, showed a similar progression of microglial changes reaching maximal intensity 7 days after trimethyl tin intoxication. Significant increases in the expression of glial fibrillary acidic protein were observed in all regions examined and typically occurred after microglial activation was already underway. We conclude that microglial and astroglial reactions which occur in response to trimethyl tin-induced neuronal necrosis are separated in time, with microglial activation preceding astrogliosis. In addition, our study stresses the importance of microglia as an endogenous source of CNS macrophages, and illustrates the merit of histochemical analysis with microglial markers for the early delineation of neurotoxicant-induced brain damage.}, Author = {McCann, M. J. and O'Callaghan, J. P. and Martin, P. M. and Bertram, T. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Macrophage Activation;Glial Fibrillary Acidic Protein;Nerve Degeneration;Trimethyltin Compounds;Comparative Study;Immunohistochemistry;Astrocytes;Rats;Not relevant;11 Glia;Microglia;Horseradish Peroxidase;Animals;Enzyme-Linked Immunosorbent Assay;Brain;Male}, Medline = {96295043}, Month = {5}, Nlm_Id = {7605074}, Number = {1}, Organization = {Procter and Gamble Company, Miami Valley Laboratories, Cincinnati, OH 45239, USA.}, Pages = {273-81}, Pii = {0306452295005269}, Pubmed = {8730724}, Title = {Differential activation of microglia and astrocytes following trimethyl tin-induced neurodegeneration}, Uuid = {C9150240-66AA-4F93-8C58-292F10E4AF46}, Volume = {72}, Year = {1996}} @article{McCarthy:2002, Abstract = {The longitudinal evolution of HIV-1 phenotypes was studied in a cohort of six vertically infected children with early onset and rapid progression of clinical disease. Among 30 viral isolates obtained from peripheral blood, tropisms for both human blood-derived cells (macrophages, T-lymphocytes), and for human neural (brain-derived) cells (microglia, astrocytes) were determined, as was chemokine co-receptor usage. All children harbored from birth macrophage-tropic isolates using the CCR5 co-receptor. Two children later developed T-cell tropic isolates with CXCR4 and CCR3 usage. While all six patients developed neurological abnormalities, only three produced neural cell tropic isolates, which used CCR5. However, early and persistent finding of both astrocyte- and microglia-tropic isolates in one patient did associate with the most rapid progression to brain atrophy among the six patients. Viral phenotypic properties determined in cell culture did not specifically predict clinical features or course, and the development of AIDS did not coincide with, or depend on, the appearance T-tropic, syncytia-inducing viruses.}, Author = {McCarthy, Micheline and He, Jun and Auger, Denise and Geffin, Rebeca and Woodson, Cristina and Hutto, Cecelia and Wood, Charles and Scott, Gwendolyn}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0146-6615}, Journal = {J Med Virol}, Keywords = {Receptors, CXCR4;Human;Prospective Studies;HIV-1;CD4 Lymphocyte Count;Astrocytes;Child, Preschool;Disease Progression;Humans;Cells, Cultured;Research Support, U.S. Gov't, Non-P.H.S.;Microglia;Female;Nervous System Diseases;Receptors, HIV;Infant;Disease Transmission, Vertical;11 Glia;Time Factors;Male;HIV Infections;Research Support, U.S. Gov't, P.H.S.;Receptors, Chemokine;Viral Load;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Receptors, CCR5}, Medline = {21918115}, Month = {5}, Nlm_Id = {7705876}, Number = {1}, Organization = {Department of Veterans Affairs Medical Center, Miami, Florida 33125, USA. mmccarth\@med.miami.edu}, Pages = {1-8}, Pii = {10.1002/jmv.2185}, Pubmed = {11920811}, Title = {Cellular tropisms and co-receptor usage of HIV-1 isolates from vertically infected children with neurological abnormalities and rapid disease progression}, Uuid = {F8B1A6DC-B546-436A-A3DD-54B7E6255F81}, Volume = {67}, Year = {2002}} @article{McConnell:1995, Author = {McConnell, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Neuron}, Keywords = {F abstr;10 Development;Cerebral Cortex/*cytology/embryology/*growth &development;Phenotype;Stem Cells;Cell Division;Animal;*Cell Differentiation;Support, U.S. Gov't, Non-P.H.S.;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Cell Movement}, Number = {4}, Organization = {Department of Biological Sciences, Stanford University, California 94305, USA.}, Pages = {761-8.}, Title = {Constructing the cerebral cortex: neurogenesis and fate determination}, Uuid = {EA744A14-7E85-46AC-97E0-E66E3E5A6367}, Volume = {15}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7576626}} @article{McConnell:1991, Abstract = {The neocortex is patterned in layers of neurons that are generated in an orderly sequence during development. This correlation between cell birthday and laminar fate prompted an examination of how neuronal phenotypes are determined in the developing cortex. At various times after labeling with [3H]thymidine, embryonic progenitor cells were transplanted into older host brains. The laminar fate of transplanted neurons correlates with the position of their progenitors in the cell cycle at the time of transplantation. Daughters of cells transplanted in S-phase migrate to layer 2/3, as do host neurons. Progenitors transplanted later in the cell cycle, however, produce daughters that are committed to their normal, deep-layer fates. Thus, environmental factors are important determinants of laminar fate, but embryonic progenitors undergo cyclical changes in their ability to respond to such cues.}, Author = {McConnell, S. K. and Kaznowski, C. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Brain Tissue Transplantation;10 Development;Research Support, Non-U.S. Gov't;G1 Phase;S Phase;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Ferrets;G2 Phase;Cell Cycle;Mitosis;Animals;Cerebral Cortex;Neurons}, Medline = {92022577}, Month = {10}, Nlm_Id = {0404511}, Number = {5029}, Organization = {Department of Biological Sciences, Stanford University, CA 94305.}, Pages = {282-5}, Pubmed = {1925583}, Title = {Cell cycle dependence of laminar determination in developing neocortex}, Uuid = {01F003F3-05C0-48E3-B82D-D2FF70FA2791}, Volume = {254}, Year = {1991}} @article{McCormick:2005, Abstract = {Neuronal activity can rapidly flip-flop between stable states. Although these semi-stable states can be generated through interactions of neuronal networks, it is now known that they can also occur in vivo through intrinsic ionic currents.}, Author = {McCormick, David A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Purkinje Cells;Ion Channels;21 Neurophysiology;Models, Neurological;Nerve Net;Humans;Brain;24 Pubmed search results 2008;Neurons;review}, Month = {4}, Nlm_Id = {9107782}, Number = {8}, Organization = {Department of Neurobiology, Kavli Center for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. david.mccormick\@yale.edu}, Pages = {R294-6}, Pii = {S0960-9822(05)00380-5}, Pubmed = {15854894}, Title = {Neuronal networks: flip-flops in the brain}, Uuid = {E2B160F6-B856-45ED-B74A-7EC405D69881}, Volume = {15}, Year = {2005}, url = {papers/McCormick_CurrBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2005.04.009}} @article{McCormick:1985, Abstract = {Slices of sensorimotor and anterior cingulate cortex from guinea pigs were maintained in vitro and bathed in a normal physiological medium. Electrophysiological properties of neurons were assessed with intracellular recording techniques. Some neurons were identified morphologically by intracellular injection of the fluorescent dye Lucifer yellow CH. Three distinct neuronal classes of electrophysiological behavior were observed; these were termed regular spiking, bursting, and fast spiking. The physiological properties of neurons from sensorimotor and anterior cingulate areas did not differ significantly. Regular-spiking cells were characterized by action potentials with a mean duration of 0.80 ms at one-half amplitude, a ratio of maximum rate of spike rise to maximum rate of fall of 4.12, and a prominent afterhyperpolarization following a train of spikes. The primary slope of initial spike frequency versus injected current intensity was 241 Hz/nA. During prolonged suprathreshold current pulses the frequency of firing adapted strongly. When local synaptic pathways were activated, all cells were transiently excited and then strongly inhibited. Bursting cells were distinguished by their ability to generate endogenous, all-or-none bursts of three to five action potentials. Their properties were otherwise very similar to regular-spiking cells. The ability to generate a burst was eliminated when the membrane was depolarized to near the firing threshold with tonic current. By contrast, hyperpolarization of regular-spiking (i.e., nonbursting) cells did not uncover latent bursting tendencies. The action potentials of fast-spiking cells were much briefer (mean of 0.32 ms) than those of the other cell types.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {McCormick, D. A. and Connors, B. W. and Lighthall, J. W. and Prince, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {gamma-Aminobutyric Acid;Electrophysiology;Animals;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;in vitro ;comparative study ;Motor Cortex;research support, non-u.s. gov't ;Action Potentials;Glutamate Decarboxylase;21 Neurophysiology;Cerebral Cortex;Somatosensory Cortex;24 Pubmed search results 2008;21 Cortical oscillations;Guinea Pigs;Gyrus Cinguli}, Month = {10}, Nlm_Id = {0375404}, Number = {4}, Pages = {782-806}, Pubmed = {2999347}, Title = {Comparative electrophysiology of pyramidal and sparsely spiny stellate neurons of the neocortex}, Uuid = {53BAA34A-90B6-4AA1-A79E-DF7824FCC8C2}, Volume = {54}, Year = {1985}, url = {papers/McCormick_JNeurophysiol1985.pdf}} @article{McCormick:1987, Abstract = {1. The post-natal development of the electrophysiological properties of cortical layer V pyramidal neurons was investigated with intracellular recordings from rat sensorimotor cortical slices, in vitro. 2. At all ages post-natally (post-natal day 1 to day 36; P1-P36) neurons were capable of generating a train of Na+-dependent action potentials in response to intracellular injection of sufficient depolarizing current. During the second and third week post-natally, these action potentials changed substantially, becoming faster in both their rising and falling phases, shorter in duration, and larger in amplitude. 3. Both mature (greater than P21) and immature (P2-P4) cortical neurones could generate Ca2+-dependent action potentials only if a substantial portion of K+ conductances were blocked. The maximum rate of rise of Ca2+ spikes also increased with age. 4. The apparent input resistance, specific membrane resistance, and membrane time constant all decreased with age from P1 to P30. Immature neurones had I-V relationships that were substantially more linear than those of adult cells, although rectification was often present in both the hyperpolarizing and depolarizing range. Inward rectification in the depolarizing range was Na+ dependent and was substantially larger in mature versus immature neurones. 5. Single, or trains of, action potentials in immature neurones were followed by short duration (10-50 ms) and long duration (1-5 s) after-hyperpolarizations (a.h.p.s) respectively. The duration of the latter appeared to decrease with age. The presence of large a.h.p.s indicates that Ca2+ entry occurs during the action potential of immature, as well as mature, neurones. 6. Responses to intracellular injection of depolarizing current pulses indicated that immature neurones have frequency versus injected current (f-I) relationships which are in general less steep than those for adult neurones and more limited in terms of the range of firing frequencies. 7. Our results are consistent with the hypothesis that there is a considerable increase in the density of voltage-dependent ionic channels underlying the electro-responsiveness of cortical pyramidal neurones during post-natal development.}, Author = {McCormick, D. A. and Prince, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Animals;Electric Conductivity;Cesium;Rats;Glutamic Acid;Tetraethylammonium Compounds;Tetrodotoxin;research support, non-u.s. gov't;Glutamates;Action Potentials;Animals, Newborn;research support, u.s. gov't, p.h.s.;Neurons;21 Neurophysiology;Membrane Potentials;Cerebral Cortex;24 Pubmed search results 2008;Tetraethylammonium;in vitro}, Month = {12}, Nlm_Id = {0266262}, Organization = {Department of Neurology, Stanford University School of Medicine, CA 94305.}, Pages = {743-62}, Pubmed = {2895811}, Title = {Post-natal development of electrophysiological properties of rat cerebral cortical pyramidal neurones}, Uuid = {0B763A9E-4818-4C63-8F45-771B02C6828A}, Volume = {393}, Year = {1987}, url = {papers/McCormick_JPhysiol1987.pdf}} @article{McCormick:2007, Abstract = {Action potentials in cortical neurons show a variable threshold and a sudden rise in membrane potential at initiation. Naundorf et al. fail to explain these features using single- or double-compartment Hodgkin-Huxley-style models, suggesting instead that they could arise from cooperative opening of Na+ channels, although there is no direct biological evidence to support this. Here we show that these so-called unique features are to be expected from Hodgkin-Huxley models if the spatial geometry and spike initiation properties of cortical neurons are taken into account--it is therefore unnecessary to invoke exotic channel-gating properties as an explanation.}, Author = {McCormick, David A. and Shu, Yousheng and Yu, Yuguo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {21 Neurophysiology;Action Potentials;Sodium Channels;Models, Neurological;Pyramidal Cells;comment;Electrophysiology;24 Pubmed search results 2008;Axons}, Month = {1}, Nlm_Id = {0410462}, Number = {7123}, Organization = {Department of Neurobiology, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06510, USA. david.mccormick\@yale.edu}, Pages = {E1-2; discussion E2-3}, Pii = {nature05523}, Pubmed = {17203021}, Title = {Neurophysiology: Hodgkin and Huxley model--still standing?}, Uuid = {AF239357-0C04-4A46-B386-22951B7DE950}, Volume = {445}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05523}} @article{McCubrey:1982, Abstract = {The frequency of ecotropic murine leukemia virus (MuLV) production in cells induced with halogenated pyrimidines has been investigated in several low leukemic strains of mice. Very few BALB/c or C57BL/6 (B6) induced embryo cells produce MuLV; this low frequency increases 10 to 50 fold in cells of the BALB/c x B6 F1 hybrid. Data from back-crosses of the F1 hybrid to each parent and from BALB/c x B6 recombinant inbred strains indicate that the phenotype of enhanced MuLV production results from interaction of two unlinked loci, dominant (+/+) alleles of which are carried by either parent. Genetic tests with BALB/c x B6 recombinant inbred strains confirm this two-locus model. The loci are designated Inc-1 and Inb-1 to signify their phenotypic detection by induction and the BALB/c or B6 strain of origin, respectively. Examination of hybrids of BALB/c and of B6 with other strains indicates that strains related in pedigree to BALB/c carry Inc-1, whereas those related to B6 carry Inb-1. Identification of genetic loci that specifically interact to enhance MuLV production after exposure to halogenated pyrimidines indicates the existence of mechanisms that regulate the induction or intracellular expression of endogenous MuLV.}, Author = {McCubrey, J. and Risser, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Mice, Inbred BALB C;Idoxuridine;Animals;Cells, Cultured;Phenotype;Leukemia;15 Retrovirus mechanism;Virus Activation;Crosses, Genetic;Embryo;Leukemia Virus, Murine;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred Strains;Mice;24 Pubmed search results 2008;Plaque Assay;15 ERVs retroelements;Research Support, Non-U.S. Gov't}, Medline = {82233707}, Month = {4}, Nlm_Id = {0413066}, Number = {4}, Pages = {881-8}, Pii = {0092-8674(82)90067-8}, Pubmed = {6284378}, Title = {Genetic interactions in induction of endogenous murine leukemia virus from low leukemic mice}, Uuid = {8DFFB311-4328-11DB-A5D2-000D9346EC2A}, Volume = {28}, Year = {1982}} @article{McElhaney:1994, Abstract = {The purpose of this study was to identify cellular sources of nitric oxide (NO) after injury to rat facial motor neurons using NADPH-diaphorase histochemistry. We employed intraneural injections of either saline or toxic ricin, followed by nerve crush, in order to produce regeneration or degeneration of facial motor neurons (FMNs), respectively. Reactive astrocytes responding to ricin-induced degeneration of FMNs showed increased NADPH-diaphorase activity while reactive astrocytes responding to axotomy (saline injection) did not. Reactive microglial cells were found not to express NADPH-diaphorase in either one of these two paradigms. We conclude that irreversible neuron injury resulting in neurodegeneration causes increased production of NO by reactive astrocytes.}, Author = {McElhaney, M. R. and Chandler, L. J. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Nerve Degeneration;Astrocytes;Ricin;Animals;Rats;Microglia;Rats, Sprague-Dawley;Not relevant;11 Glia;Male;Nerve Regeneration;NADPH Dehydrogenase;Support, Non-U.S. Gov't;Histocytochemistry;Support, U.S. Gov't, P.H.S.;Motor Neurons;Nerve Crush;Facial Nerve;Ligands}, Medline = {95183230}, Month = {10}, Nlm_Id = {7600130}, Number = {1}, Organization = {Department of Comparative and Experimental Pathology, College of Veterinary Medicine, University of Florida, Gainesville 32610.}, Pages = {67-70}, Pubmed = {7877765}, Title = {Astrocytes but not microglia express NADPH-diaphorase activity after motor neuron injury in the rat}, Uuid = {77F92E3E-C615-4542-9F2E-372211CD07ED}, Volume = {180}, Year = {1994}} @article{McGeer:1998, Abstract = {Lesions in such chronic neurodegenerative disorders as Alzheimer disease, Parkinson disease, the parkinsonism dementia complex of Guam and amyotrophic lateral sclerosis have associated with them a variety of proteins known to be involved in inflammatory processes. This is particularly true of Alzheimer disease where inflammatory reactions are thought to be important contributors to the neuronal loss. They include complement proteins, complement inhibitors, acute phase reactants, inflammatory cytokines, proteases and protease inhibitors. Studies of cultured human astrocytes and microglia, obtained from postmortem brain, have established that nearly all of these proteins are produced by one or another of these cell types. Human neurons also produce many inflammatory proteins and their inhibitors, creating complex interactions. Accumulations of amyloid and extracellular tangles apparently act as irritants, causing the activation of complement, the initiation of reactive changes in microglia, and the release of potentially neurotoxic products. Such products include the membrane attack complex, oxygen free radicals and excess glutamate. Twenty epidemiological studies that have been published to data indicate that populations taking antiinflammatory drugs have a significantly reduced prevalence of Alzheimer disease or a slower mental decline. One small clinical trial with indomethacin showed arrest of the disease over a 6 month period. Therapeutic intervention in key inflammatory processes holds great promise for the amelioration of Alzheimer disease and possibly other neurodegenerative disorders.}, Author = {McGeer, P. L. and McGeer, E. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0303-6995}, Journal = {J Neural Transm Suppl}, Keywords = {Human;Inflammation;Models, Neurological;Astrocytes;Models, Immunological;Microglia;review, tutorial;Alzheimer Disease;Parkinson Disease;Support, Non-U.S. Gov't;Brain;11 Glia;Neurons;review}, Medline = {99067910}, Nlm_Id = {0425126}, Organization = {Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, Canada.}, Pages = {159-66}, Pubmed = {9850924}, Title = {Mechanisms of cell death in Alzheimer disease--immunopathology}, Uuid = {32FC2B8F-19B3-414B-B040-902C82B5A8A2}, Volume = {54}, Year = {1998}} @article{McGuire:2001, Abstract = {In this issue of Neuron, report that forebrain-specific Presenilin-1 conditional knockout mice show defects in enrichment-induced neurogenesis in the dentate gyrus. This defect in neurogenesis is associated with enhanced fear memory of contextual cues when animals are subjected to enrichment between training and testing. The authors suggest that neurogenesis in the adult dentate gyrus may serve to clear out old memory traces from the hippocampus, thus leaving the hippocampus available for new memory processing.}, Author = {McGuire, S. E. and Davis, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Neuron}, Keywords = {Memory/*physiology;Alzheimer Disease/drug therapy/metabolism;Human;Membrane Proteins/*metabolism;Animal;Prosencephalon/*metabolism;04 Adult neurogenesis factors;C abstr}, Number = {5}, Organization = {Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.}, Pages = {763-5.}, Title = {Presenilin-1 and memories of the forebrain}, Uuid = {A9A66685-FEBC-4469-9779-40C9B46BE822}, Volume = {32}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11738022}} @article{McKay:2004, Abstract = {The vitamin biotin is an endogenous molecule that acts as an important cofactor for several carboxylases in the citric acid cycle. Disorders of biotin metabolism produce neurological symptoms that range from ataxia to sensory loss, suggesting the presence of biotin in specific functional systems of the CNS. Although biotin has been described in some cells of nonmammalian nervous systems, the distribution of biotin in mammalian CNS is virtually unknown. We report the presence of biotin in select regions of rat CNS, as revealed with a monoclonal antibody directed against biotin and with avidin- and streptavidin-conjugated labels. Detectable levels of biotin were primarily found caudal to the diencephalon, with greatest expression in the cerebellar motor system and several brainstem auditory nuclei. Biotin was found as a somatic label in cerebellar Purkinje cells, in cell bodies and proximal dendrites of cerebellar deep nuclear neurons, and in red nuclear neurons. Biotin was detected in cells of the spiral ganglion, somata and proximal dendrites of cells in the cochlear nuclei, superior olivary nuclei, medial nucleus of the trapezoid body, and nucleus of the lateral lemniscus. Biotin was further found in pontine nuclei and fiber tracts, the substantia nigra pars reticulata, lateral mammillary nucleus, and a small number of hippocampal interneurons. Biotin was detected in glial cells of major tract systems throughout the brain but was most prominent in tracts of the hindbrain. Biotin is thus expressed in select regions of rat CNS with a distribution that correlates to the known clinical sequelae associated with biotin deficiencies.}, Author = {McKay, Bruce E. and Molineux, Michael L. and Turner, Ray W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Avidin;Streptavidin;Tissue Distribution;Rats, Sprague-Dawley;Central Nervous System;Comparative Study;Immunohistochemistry;Rats;Biotin;Histocytochemistry;Support, Non-U.S. Gov't;Male;Animals;Neurons;23 Technique}, Month = {5}, Nlm_Id = {0406041}, Number = {1}, Organization = {Neuroscience Research Group, University of Calgary, Calgary, Alberta T2N 4N1, Canada.}, Pages = {86-96}, Pubmed = {15067720}, Title = {Biotin is endogenously expressed in select regions of the rat central nervous system}, Uuid = {E878B101-02EA-43BC-97C8-9FFA24C3143D}, Volume = {473}, Year = {2004}, url = {papers/McKay_JCompNeurol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20109}} @article{McKone:2007, Abstract = {Does face recognition involve face-specific cognitive and neural processes ('domain specificity') or do faces only seem special because people have had more experience of individuating them than they have of individuating members of other homogeneous object categories ('the expertise hypothesis')? Here, we summarize new data that test these hypotheses by assessing whether classic face-selective effects - holistic processing, recognition impairments in prosopagnosia and fusiform face area activation - remain face selective in comparison with objects of expertise. We argue that evidence strongly supports domain specificity rather than the expertise hypothesis. We conclude that the crucial social function of face recognition does not reflect merely a general practice phenomenon and that it might be supported by evolved mechanisms (visual or nonvisual) and/or a sensitive period in infancy.}, Author = {McKone, Elinor and Kanwisher, Nancy and Duchaine, Bradley C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1364-6613}, Journal = {Trends Cogn Sci}, Keywords = {Neurons;Photic Stimulation;Prosopagnosia;research support, non-u.s. gov't;Pattern Recognition, Visual;Specialties, Medical;21 Neurophysiology;24 Pubmed search results 2008;Face;research support, n.i.h., extramural;Brain Mapping;Animals;Brain;Humans;review;Facial Expression}, Month = {1}, Nlm_Id = {9708669}, Number = {1}, Organization = {School of Psychology, Australian National University, ACT 0200, Australia. elinor.mckone\@anu.edu.au}, Pages = {8-15}, Pii = {S1364-6613(06)00300-7}, Pubmed = {17129746}, Title = {Can generic expertise explain special processing for faces?}, Uuid = {631C0DAA-01F2-460C-A7C0-F1FE5867486D}, Volume = {11}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tics.2006.11.002}} @article{McLaren:2001, Abstract = {Much recent interest has focused on whether stem cell therapy could alleviate or even cure common degenerative diseases. This has been accompanied by debate on the ethics of destructive research on early human embryos. Stem cells derived from various sources raise different ethical issues, but their contribution to medical research could be immense. Any use of stem cells should be subject to appropriate scientific and ethical review. 0028-0836 Journal Article Review Review, Tutorial}, Author = {McLaren, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Nature}, Keywords = {*Bioethics;Morals;Embryo/cytology;10 Development;F abstr;Public Policy;Human;*Research/legislation &jurisprudence/standards;*Stem Cells;Sociology;*Ethics, Medical}, Number = {6859}, Organization = {Wellcome/CRC Institute, University of Cambridge, UK. a.mclaren\@welc.cam.ac.uk}, Pages = {129-31}, Pubmed = {11689959}, Title = {Ethical and social considerations of stem cell research}, Uuid = {9CE01674-47C0-48F3-8630-1846EA6E40EC}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689959}} @article{McLean:1994, Abstract = {Serotonin has been postulated to influence several developmental parameters. The potential role of serotonin in the development of the rat olfactory bulb, a simple cortical structure, was determined following selective depletion of serotonin to the olfactory bulb of neonate rats. In the neonate, 5,7-dHT was injected into the anterior olfactory nucleus to selectively destroy serotonergic axons leading to the bulb. Following survival of 5 days to 3 months, the rats were sacrificed and analyzed by immunocytochemical markers, Nissl stain, Golgi impregnation, and image analysis. The serotonin depletions had no significant effect on the cytoarchitecture of the bulb or on neuronal or glial cell growth. In addition, the depletions did not affect neuronal migration or differentiation (overall length of dendrites, branch points, or dendritic spines) of cell populations in the bulb. These findings suggest that serotonin does not, by itself, affect the overall development of cellular elements in the bulb, although this study does not rule out the possibility that serotonin may affect other parameters of development. eng Journal Article}, Author = {McLean, J. H. and Darby-King, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Journal = {Brain Res Bull}, Keywords = {Neuroglia/cytology/physiology;Cell Differentiation;Rats, Sprague-Dawley;Rats;Female;Serotonin/deficiency/*physiology;Olfactory Bulb/*cytology/*physiology;Neurons/cytology/*physiology;Aging/physiology;Animal;Animals, Newborn;I abstr;Support, Non-U.S. Gov't;Injections;5,7-Dihydroxytryptamine/pharmacology;Male;13 Olfactory bulb anatomy}, Number = {3}, Organization = {Division of Basic Medical Sciences, Memorial University of Newfoundland, St. John's, Canada.}, Pages = {249-59.}, Title = {Lack of evidence for serotonergic effect on the cellular development of the olfactory bulb in the postnatal rat}, Uuid = {F51085E5-6B23-4502-8619-1259D3E8160E}, Volume = {34}, Year = {1994}} @article{McMahon:2007, Abstract = {During development there is a clear correlation between position of dividing progenitor cells, mode of division and developmental potential, suggesting that the local environment of progenitor cells may influence their cell fate [ 17 (6), 639-647]. The contribution of these conditions was investigated here by transplantation of radial glial progenitor cells into isotopic, isochronic, heterotopic and heterochronic environment conditions. Neuronal cells were removed from E14 spinal cords using negative immunoselection. The remaining radial glia were transplanted into the ventricular system of host embryos and pups. Distance of migration as well as morphological and antigenic phenotype of transplanted radial glia was examined after various survival times post transplantation. Host age clearly influenced migration and differentiation of transplant cells, with transplant cells migrating further in younger hosts and differentiating earlier in older aged host environments. Evidence is presented showing that most transplanted spinal cord radial glia give rise to astrocytes. In addition some transplanted radial glia were shown to give rise to neurons in spinal cord regions. Radial glia did not appear to generate neurons in the brains of host animals until postnatal ages, perhaps because transplanted radial glia were isolated from spinal cord and thus may not have been influenced to behave as endogenous radial glia in the brain which commonly produce neurons.}, Author = {McMahon, Siobhan S. and McDermott, Kieran W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Anatomy and Biosciences Institute, University College Cork, Cork, Ireland.}, Pages = {128-36}, Pii = {S0014-4886(06)00467-5}, Pubmed = {17010971}, Title = {Developmental potential of radial glia investigated by transplantation into the developing rat ventricular system in utero}, Uuid = {8ADF0455-442F-4185-8257-23294969647E}, Volume = {203}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2006.07.029}} @article{McMahon:2002, Abstract = {The contribution of peripheral macrophage was assessed in cuprizone intoxication, a model of demyelination and remyelination in which the blood-brain barrier remains intact. Flow cytometry of brain cells isolated from cuprizone-treated mice revealed an increase in the percentage of Mac-1(+)/CD45(hi) peripheral macrophage. To confirm these results in situ, C57BL/6 mice were lethally irradiated, transplanted with bone marrow from GFP-transgenic mice, and exposed to cuprizone. GFP(+) peripheral macrophages were seen in the CNS after 2 weeks of treatment, and infiltration continued through 6 weeks. While the peripheral macrophages were far outnumbered by the resident microglia, their recruitment across the blood-brain barrier alludes to a potentially important role.}, Author = {McMahon, Eileen J. and Suzuki, Kinuko and Matsushima, Glenn K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Antigens, CD45;Animals;Macrophages;Bone Marrow Transplantation;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Chemotaxis, Leukocyte;Disease Models, Animal;Blood-Brain Barrier;Antigens, CD3;Radiation Chimera;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Macrophage-1 Antigen;Male;Demyelinating Autoimmune Diseases, CNS;Flow Cytometry;Mice;Central Nervous System;Research Support, Non-U.S. Gov't}, Medline = {22213662}, Month = {9}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Microbiology and Immunology, University of North Carolina, 27599, Chapel Hill, NC, USA}, Pages = {32-45}, Pii = {S0165572802002059}, Pubmed = {12225886}, Title = {Peripheral macrophage recruitment in cuprizone-induced CNS demyelination despite an intact blood-brain barrier}, Uuid = {B60654D4-FDC9-49CF-B8F6-160A01A4CD0F}, Volume = {130}, Year = {2002}} @article{McMillian:1994, Abstract = {Reactive gliosis is a powerful response to brain injury and subsequent neuronal damage in vivo. Neuronal cell cultures are now well established as assays to study this process in vitro. However, equivalent studies of purified glial cell populations have only recently been achieved, following the realization that glial cells produce many of the neuropeptides, transmitters and growth factors that are produced also by neurons. There is now scope for studies in vitro that use mixed, identified populations of glial and neuronal cells to dissect the interactions between the two. Such cultures also lend themselves to assays for potential therapeutic strategies for brain injury that take account of all the different cell types found in the brain.}, Author = {McMillian, M. K. and Thai, L. and Hong, J. S. and O'Callaghan, J. P. and Pennypacker, K. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {11 Glia;Neurotransmitters;Nerve Tissue Proteins;Astrocytes;Neuropeptides;Gliosis;Rats;Growth Substances;Microglia;Animals, Suckling;Cell Death;Growth Inhibitors;Animals;Cells, Cultured;review, tutorial;Neurons;review}, Medline = {94295082}, Month = {4}, Nlm_Id = {7808616}, Number = {4}, Organization = {Laboratory of Molecular and Integrative Neurosciences, National Institute of Environmental Health Sciences, National Institutes of Health.}, Pages = {138-42}, Pubmed = {7517589}, Title = {Brain injury in a dish: a model for reactive gliosis}, Uuid = {50CADAB1-EA03-499A-95C6-990AABE2A2B0}, Volume = {17}, Year = {1994}} @article{McNamara:1994, Author = {McNamara, J. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Epilepsy;Neurons;Brain Diseases;Potassium;21 Epilepsy;21 Neurophysiology;Terminology;Hippocampus;Models, Neurological;Research Support, U.S. Gov't, P.H.S.;Research Support, U.S. Gov't, Non-P.H.S.;Animals;Humans;24 Pubmed search results 2008;review;Sclerosis}, Medline = {94267505}, Month = {6}, Nlm_Id = {8102140}, Number = {6}, Organization = {Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 27710.}, Pages = {3413-25}, Pubmed = {8207463}, Title = {Cellular and molecular basis of epilepsy}, Uuid = {28ECF8D2-73A8-4A7D-9AF4-500B5FB02D83}, Volume = {14}, Year = {1994}, url = {papers/McNamara_JNeurosci1994.pdf}} @article{McNamara:2000, Abstract = {We have previously shown that the myristoylated alanine-rich C kinase substrate, a primary protein kinase C substrate in brain that binds and cross-links filamentous actin, is enriched in neuronal growth cones and is developmentally regulated in brain. Here we examined myristoylated alanine-rich C kinase substrate expression in the facial motor nucleus during axonal regeneration following facial nerve axotomy or facial nerve resection lesions, which impede regeneration, or following motor neuron degeneration induced by the retrograde neurotoxin ricin. For comparative purposes, the protein kinase C substrates myristoylated alanine-rich C kinase substrate-like protein and growth-associated protein-43 were examined in parallel. Myristoylated alanine-rich C kinase substrate messenger RNA exhibited a robust increase in both neurons and non-neuronal cells in the facial motor nucleus beginning four days after axotomy, peaked at seven days (2.5-fold), and declined back to baseline levels by 40 days. Myristoylated alanine-rich C kinase substrate protein similarly exhibited a twofold elevation in the facial motor nucleus determined four and 14 days post-axotomy. Following nerve resection, myristoylated alanine-rich C kinase substrate messenger RNA levels increased at seven days and returned to baseline levels by 40 days. Unlike myristoylated alanine-rich C kinase substrate messenger RNA, myristoylated alanine-rich C kinase substrate-like messenger RNA levels did not increase in the facial motor nucleus at any time point following nerve axotomy or resection, whereas growth-associated protein-43 messenger RNA exhibited a rapid (one day) and prolonged (40 days) elevation in facial motor nucleus neurons following either nerve axotomy or resection. Ricin-induced degeneration of facial motor neurons elevated myristoylated alanine-rich C kinase substrate and myristoylated alanine-rich C kinase substrate-like messenger RNAs in both microglia (lectin-positive) and astrocytes (glial fibrillary acidic protein-positive).Collectively, these data demonstrate that myristoylated alanine-rich C kinase substrate exhibits a unique expression profile in the facial motor nucleus following facial nerve lesions, and it is proposed that myristoylated alanine-rich C kinase substrate may serve to mediate actin-membrane cytoskeletal plasticity in both neurons and glial cells in response to protein kinaseC-mediated signaling during nerve regeneration and degeneration.}, Author = {McNamara, R. K. and Jiang, Y. and Streit, W. J. and Lenox, R. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {GAP-43 Protein;Nerve Degeneration;Animals;Up-Regulation;Rats;Proteins;RNA, Messenger;Not relevant;11 Glia;Male;Nerve Regeneration;Support, Non-U.S. Gov't;Axotomy;Neuroglia;Support, U.S. Gov't, P.H.S.;Motor Neurons;Membrane Proteins;Facial Nerve}, Medline = {20291264}, Nlm_Id = {7605074}, Number = {3}, Organization = {Department of Psychiatry, University of Pennsylvania School of Medicine, Clinical Research Building, Philadelphia, PA 19104-6140, USA. rkm\@mail.med.upenn.edu}, Pages = {581-9}, Pii = {S0306452200000397}, Pubmed = {10828540}, Title = {Facial motor neuron regeneration induces a unique spatial and temporal pattern of myristoylated alanine-rich C kinase substrate expression}, Uuid = {45BF0640-8455-4E2A-B483-E932DCA725A5}, Volume = {97}, Year = {2000}} @article{McNeill:1988, Abstract = {Loss of dopaminergic neurons from the pars compacta of the substantia nigra is the pathological hallmark of Parkinson's disease (PD) and results in a partial deafferentation to the striatum. Since deafferentation is known to induce transynaptic atrophy of postsynaptic cells, we examined by Golgi impregnation the morphology of medium spiny I (MSI) striatal neurons, the principal target population for both nigrostriatal and corticostriatal fibers. Our quantitative data indicate that the dendritic arbor of MSI neurons in the putamen is significantly reduced in both length and number and MSI neurons are morphologically characterized by truncated dendrites with few dendritic spines and irregular, bulbous swellings. These data provide morphological evidence for the atrophy of striatal dendrites in PD and may explain, in part, the declining efficacy of chronic L-DOPA replacement therapy in advanced PD.}, Author = {McNeill, T. H. and Brown, S. A. and Rafols, J. A. and Shoulson, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Reference Values;10 Development;Dendrites;Aged;Aged, 80 and over;10 Spiny stellate;Research Support, U.S. Gov't, P.H.S.;Corpus Striatum;Atrophy;11 Glia;Parkinson Disease;10 Structural plasticity;Humans;G;24 Pubmed search results 2008;Neurons}, Medline = {88327382}, Month = {7}, Nlm_Id = {0045503}, Number = {1}, Organization = {Department of Neurology, University of Rochester, NY 14642.}, Pages = {148-52}, Pubmed = {3416180}, Title = {Atrophy of medium spiny I striatal dendrites in advanced Parkinson's disease}, Uuid = {AE810627-6F60-4E7B-AB48-66B533AFB704}, Volume = {455}, Year = {1988}} @article{McQuiston:2001, Abstract = {In the mammalian olfactory bulb, glomeruli are surrounded by a heterogeneous population of interneurons called juxtaglomerular neurons. As they receive direct input from olfactory receptor neurons and connect with mitral cells, they are involved in the initial stages of olfactory information processing, but little is known about their detailed physiological properties. Using whole cell patch-clamp techniques, we recorded from juxtaglomerular neurons in rat olfactory bulb slices. Based on their response to depolarizing pulses, juxtaglomerular neurons could be divided into two physiological classes: bursting and standard firing. When depolarized, the standard firing neurons exhibited a range of responses: accommodating, nonaccommodating, irregular firing, and delayed to firing patterns of action potentials. Although the firing pattern was not rigorously predictive of a particular neuronal morphology, most short axon cells fired accommodating trains of action potentials, while most delayed to firing cells were external tufted cells. In contrast to the standard firing neurons, bursting neurons produced a calcium-channel-dependent low-threshold spike when depolarized either by current injection or by spontaneous or evoked postsynaptic potentials. Bursting neurons also could oscillate spontaneously. Most bursting cells were either periglomerular cells or external tufted cells. Based on their mode of firing and placement in the bulb circuit, these bursting cells are well situated to drive synchronous oscillations in the olfactory bulb. 21486690 0022-3077 Journal Article}, Author = {McQuiston, A. R. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {J Neurophysiol}, Keywords = {Quinoxalines/pharmacology;2-Amino-5-phosphonovalerate/pharmacology;13 Olfactory bulb anatomy;Rats;Excitatory Amino Acid Antagonists/pharmacology;Nickel/pharmacology;Animal;Cell Size/physiology;Patch-Clamp Techniques;Action Potentials/drug effects/physiology;Nootropic Agents/pharmacology;Periodicity;Rats, Sprague-Dawley;Male;Olfactory Bulb/cytology/*physiology;Interneurons/cytology/*physiology;Anesthetics, Local/pharmacology;Excitatory Postsynaptic Potentials/drug effects/physiology;Lidocaine/*analogs &derivatives/pharmacology;I both;Choline/pharmacology}, Number = {4}, Organization = {Howard Hughes Medical Institute and Department of Neurobiology, Duke University School of Medicine, Durham, North Carolina 27710, USA.}, Pages = {1899-907}, Title = {Electrophysiology of interneurons in the glomerular layer of the rat olfactory bulb}, Uuid = {5A557FE3-8D3D-4C59-8ECB-4887A1E338A2}, Volume = {86}, Year = {2001}, url = {papers/McQuiston_JNeurophysiol2001.pdf}} @article{McTigue:1998, Abstract = {Functional loss after spinal cord injury (SCI) is caused, in part, by demyelination of axons surviving the trauma. Neurotrophins have been shown to induce oligodendrogliagenesis in vitro, but stimulation of oligodendrocyte proliferation and myelination by these factors in vivo has not been examined. We sought to determine whether neurotrophins can induce the formation of new oligodendrocytes and myelination of regenerating axons after SCI in adult rats. In this study, fibroblasts producing neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), ciliary neurotrophic factor, nerve growth factor, basic fibroblast growth factor, or beta-galactosidase (control grafts) were transplanted subacutely into the contused adult rat spinal cord. At 10 weeks after injury, all transplants contained axons. NT-3 and BDNF grafts, however, contained significantly more axons than control or other growth factor-producing grafts. In addition, significantly more myelin basic protein-positive profiles were detected in NT-3 and BDNF transplants, suggesting enhanced myelination of ingrowing axons within these neurotrophin-producing grafts. To determine whether augmented myelinogenesis was associated with increased proliferation of oligodendrocyte lineage cells, bromodeoxyuridine (BrdU) was used to label dividing cells. NT-3 and BDNF grafts contained significantly more BrdU-positive oligodendrocytes than controls. The association of these new oligodendrocytes with ingrowing myelinated axons suggests that NT-3- and BDNF-induced myelinogenesis resulted, at least in part, from expansion of oligodendrocyte lineage cells, most likely the endogenous oligodendrocyte progenitors. These findings may have significant implications for chronic demyelinating diseases or CNS injuries.}, Author = {McTigue, D. M. and Horner, P. J. and Stokes, B. T. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Neurosci}, Keywords = {Myelin Sheath/*physiology;Fibroblasts/drug effects;Nerve Growth Factors/*pharmacology;Rats;Schwann Cells/drug effects;Spinal Cord Injuries/*drug therapy;Female;Animal;Brain-Derived Neurotrophic Factor/*pharmacology;Oligodendroglia/cytology/drug effects;Neurotrophin 3;G abstr;11 Glia;Rats, Inbred F344;Cell Lineage;Cell Division/physiology;Support, Non-U.S. Gov't;Contusions/*drug therapy;Nerve Regeneration/*drug effects;Support, U.S. Gov't, P.H.S.;Axons/drug effects}, Number = {14}, Organization = {Department of Physiology, Ohio State University, Columbus, Ohio 43210, USA.}, Pages = {5354-65.}, Title = {Neurotrophin-3 and brain-derived neurotrophic factor induce oligodendrocyte proliferation and myelination of regenerating axons in the contused adult rat spinal cord}, Uuid = {6A320F65-A359-4D2A-AE81-9091E757CFA8}, Volume = {18}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9651218%20http://www.jneurosci.org/cgi/content/full/18/14/5354}} @article{Mechawar:2001, Abstract = {A recently developed method for determining the length of cholinergic axons and number of cholinergic axon varicosities (terminals) in brain sections immunostained for choline acetyltransferase was used to estimate the areal and laminar densities of the cholinergic innervation in rat frontal (motor), parietal (somatosensory) and occipital (visual) cortex at different postnatal ages. This cortical innervation showed an early beginning, a few immunostained fibers being already present in the cortical subplate at birth. In the first two postnatal weeks, it developed rapidly along three parameters: a progressive increase in the number of varicosities per unit length of axon, and a lengthening and branching of the axons. Between postnatal days 4 and 16, the number of varicosities increased steadily from two to four per 10 microm of cholinergic axon. The mean densities of cholinergic axons increased from 1.4 to 9.6, 1.7 to 9.3 and 0.7 to 7.2 m/mm(3), and the corresponding densities of varicosities from 0.4 to 3.9, 0.4 to 3.5, and 0.2 to 2.6x10(6)/mm(3) in the frontal, parietal and occipital areas, respectively. The rate of growth was maximal during these first two weeks, after which the laminar pattern characteristic of each area appeared to be established. Adult values were almost reached by postnatal day 16 in the parietal cortex, but maturation proceeded further in the frontal and particularly in the occipital cortex.These quantitative data on the ingrowth and maturation of the cholinergic innervation in postnatal rat cerebral cortex substantiate a role for acetylcholine in the development of this brain region and emphasize the striking growth capacity of individual cholinergic neurons.}, Author = {Mechawar, N. and Descarries, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Cerebral Cortex;24 Pubmed search results 2008;Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;Rats;Immunohistochemistry;Neural Pathways;Cholinergic Fibers;Occipital Lobe;Choline O-Acetyltransferase;Parietal Lobe;Male;Age Factors;Animals;Acetylcholine;Frontal Lobe}, Medline = {21603174}, Nlm_Id = {7605074}, Number = {4}, Organization = {D{\'e}partement de pathologie, and Centre de recherche en sciences neurologiques, Facult{\'e} de m{\'e}decine, Universit{\'e} de Montr{\'e}al, P.O. Box 6128, Succursale Centre-ville, H3C 3J7, Montreal, QC, Canada.}, Pages = {555-67}, Pii = {S030645220100389X}, Pubmed = {11738494}, Title = {The cholinergic innervation develops early and rapidly in the rat cerebral cortex: a quantitative immunocytochemical study}, Uuid = {B51620AA-709A-4CF5-89E4-CF3C18FEF38F}, Volume = {108}, Year = {2001}} @article{Meeker:1999, Abstract = {Microglia are thought to play an important role in neurodegenerative changes due to infection with human or animal immunodeficiency viruses. Using feline immunodeficiency virus and cat neural cultures, we observed a dramatic increase in the accumulation of microglia from a basal rate of 5-7\%day(-1) to 25-126\%day(-1). Both live virus and heat-inactivated virus induced proliferation. Negligible proliferation was seen in purified microglial cultures. Conditioned medium from astrocytes or mixed neural cultures treated with feline immunodeficiency virus stimulated the proliferation of purified microglia. Disease progression may be facilitated by early non-infectious interactions of lentiviruses with neural tissue that promote the activation and proliferation of microglia.}, Author = {Meeker, R. B. and Azuma, Y. and Bragg, D. C. and English, R. V. and Tompkins, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Cats;Female;AIDS Dementia Complex;Astrocytes;Cell Division;Tumor Necrosis Factor-alpha;Microglia;Pregnancy;Immunodeficiency Virus, Feline;11 Glia;Cells, Cultured;Bromodeoxyuridine;Cerebral Cortex;Animals;24 Pubmed search results 2008}, Medline = {20046776}, Month = {11}, Nlm_Id = {8109498}, Number = {1}, Organization = {Department of Neurology, University of North Carolina, Chapel Hill 27599, USA.}, Pages = {15-26}, Pii = {S0165572899001265}, Pubmed = {10580809}, Title = {Microglial proliferation in cortical neural cultures exposed to feline immunodeficiency virus}, Uuid = {02F4E76B-8278-4B68-94AD-F2309D79021F}, Volume = {101}, Year = {1999}, url = {papers/Meeker_JNeuroimmunol1999.pdf}} @article{Meencke:1992, Author = {Meencke, H. J. and Veith, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0922-9833}, Journal = {Epilepsy Res Suppl}, Keywords = {Spasms, Infantile;10 Development;Cell Differentiation;Syndrome;Child, Preschool;Humans;Brain;Child;Epilepsy;Infant;Cell Count;Cell Movement;10 genetics malformation;Cerebral Cortex;Neurons;Adult;Infant, Newborn;24 Pubmed search results 2008;Adolescent}, Nlm_Id = {8913231}, Organization = {Department of Neurology, Universit{\"a}tsklinikum Rudolf-Virchow, Free University of Berlin, Germany.}, Pages = {31-9; discussion 39-40}, Pubmed = {1285910}, Title = {Migration disturbances in epilepsy}, Uuid = {4CF65CD4-0BCB-4219-B70B-04B0FE500C66}, Volume = {9}, Year = {1992}} @article{Meeren:2002, Abstract = {Absence seizures are the most pure form of generalized epilepsy. They are characterized in the electroencephalogram by widespread bilaterally synchronous spike-wave discharges (SWDs), which are the reflections of highly synchronized oscillations in thalamocortical networks. To reveal network mechanisms responsible for the initiation and generalization of the discharges, we studied the interrelationships between multisite cortical and thalamic field potentials recorded during spontaneous SWDs in the freely moving WAG/Rij rat, a genetic model of absence epilepsy. Nonlinear association analysis revealed a consistent cortical "focus" within the peri-oral region of the somatosensory cortex. The SWDs recorded at other cortical sites consistently lagged this focal site, with time delays that increased with electrode distance (corresponding to a mean propagation velocity of 1.4 m/sec). Intra-thalamic relationships were more complex and could not account for the observed cortical propagation pattern. Cortical and thalamic sites interacted bi-directionally, whereas the direction of this coupling could vary throughout one seizure. However, during the first 500 msec, the cortical focus was consistently found to lead the thalamus. These findings argue against the existence of one common subcortical pacemaker for the generation of generalized spike-wave discharges characteristic for absence seizures in the rat. Instead, the results suggest that a cortical focus is the dominant factor in initiating the paroxysmal oscillation within the corticothalamic loops, and that the large-scale synchronization is mediated by ways of an extremely fast intracortical spread of seizure activity. Analogous mechanisms may underlie the pathophysiology of human absence epilepsy.}, Author = {Meeren, Hanneke K. M. and Pijn, Jan Pieter M. and Van Luijtelaar, Egidius L. J. M. and Coenen, Anton M. L. and Lopes da Silva, Fernando H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Wakefulness;Electric Stimulation;Epilepsies, Partial;Evoked Potentials;Animals;Rats;Signal Processing, Computer-Assisted;Nonlinear Dynamics;Rats, Inbred Strains;Biological Clocks;Disease Models, Animal;Time Factors;research support, non-u.s. gov't ;Thalamus;Action Potentials;Nerve Net;Cerebral Cortex;21 Neurophysiology;Evoked Potentials, Somatosensory;Epilepsy, Absence;24 Pubmed search results 2008;Electroencephalography;Electrodes, Implanted;Brain Mapping}, Month = {2}, Nlm_Id = {8102140}, Number = {4}, Organization = {Department of Comparative and Physiological Psychology, Nijmegen Institute of Cognition and Information, University of Nijmegen, 6500 HE Nijmegen, The Netherlands. h.meeren\@vumc.nl.}, Pages = {1480-95}, Pii = {22/4/1480}, Pubmed = {11850474}, Title = {Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats}, Uuid = {D6C8E565-7ADD-40A7-82BC-87E36E835D4B}, Volume = {22}, Year = {2002}} @article{Mehmet:2000, Author = {Mehmet, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Nature}, Keywords = {Amyloid beta-Protein/metabolism;Receptors, Cytoplasmic and Nuclear/metabolism;07 Excitotoxicity Apoptosis;Alzheimer Disease/enzymology;*Apoptosis;Calcium-Binding Proteins/metabolism;E-13;Caspases/*metabolism;Animal;Receptors, Peptide/metabolism;Endoplasmic Reticulum/*metabolism;Mice}, Number = {6765}, Pages = {29-30.}, Title = {Caspases find a new place to hide}, Uuid = {A2C589B2-034F-4818-BDFB-CC9807681025}, Volume = {403}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10638735}} @article{Mehta:2002, Abstract = {In the vast majority of brain areas, the firing rates of neurons, averaged over several hundred milliseconds to several seconds, can be strongly modulated by, and provide accurate information about, properties of their inputs. This is referred to as the rate code. However, the biophysical laws of synaptic plasticity require precise timing of spikes over short timescales (<10 ms). Hence it is critical to understand the physiological mechanisms that can generate precise spike timing in vivo, and the relationship between such a temporal code and a rate code. Here we propose a mechanism by which a temporal code can be generated through an interaction between an asymmetric rate code and oscillatory inhibition. Consistent with the predictions of our model, the rate and temporal codes of hippocampal pyramidal neurons are highly correlated. Furthermore, the temporal code becomes more robust with experience. The resulting spike timing satisfies the temporal order constraints of hebbian learning. Thus, oscillations and receptive field asymmetry may have a critical role in temporal sequence learning.}, Author = {Mehta, M. R. and Lee, A. K. and Wilson, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {research support, u.s. gov't, p.h.s. ;Consciousness;21 Neurophysiology;Kinetics;Rats, Long-Evans;Action Potentials;Rats;research support, non-u.s. gov't ;Computer Simulation;Models, Neurological;Time Factors;Neuronal Plasticity;Motor Activity;Learning;Pyramidal Cells;Animals;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0410462}, Number = {6890}, Organization = {Center for Learning & Memory, Department of Brain & Cognitive Sciences, RIKEN-MIT Neuroscience Center, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. mayank\@mit.edu}, Pages = {741-6}, Pii = {nature00807}, Pubmed = {12066185}, Title = {Role of experience and oscillations in transforming a rate code into a temporal code}, Uuid = {7E85C0BD-7721-4573-9FF4-5E4B9226201B}, Volume = {417}, Year = {2002}, url = {papers/Mehta_Nature2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature00807}} @article{Mehta:2005, Abstract = {The exocyst is a complex of proteins originally identified in yeast that has been implicated in polarized secretion. Components of the exocyst have been implicated in neurite outgrowth, cell polarity, and cell viability. We have isolated an exocyst component, sec15, in a screen for genes required for synaptic specificity. Loss of sec15 causes a targeting defect of photoreceptors that coincides with mislocalization of specific cell adhesion and signaling molecules. Additionally, sec15 mutant neurons fail to localize other exocyst members like Sec5 and Sec8, but not Sec6, to neuronal terminals. However, loss of sec15 does not cause cell lethality in contrast to loss of sec5 or sec6. Our data suggest a role of Sec15 in an exocyst-like subcomplex for the targeting and subcellular distribution of specific proteins. The data also show that functions of other exocyst components persist in the absence of sec15, suggesting that different exocyst components have separable functions.}, Author = {Mehta, Sunil Q. and Hiesinger, P. Robin and Beronja, Slobodan and Zhai, R. Grace and Schulze, Karen L. and Verstreken, Patrik and Cao, Yu and Zhou, Yi and Tepass, Ulrich and Crair, Michael C. and Bellen, Hugo J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Exocytosis;Animals;Synapses;Humans;Sequence Homology, Amino Acid;comparative study;Protein Transport;Mutation;research support, non-u.s. gov't;research support, u.s. gov't, p.h.s.;Blotting, Western;Neurons;Drosophila;Microscopy, Electron, Transmission;Polymerase Chain Reaction;Amino Acid Sequence;24 Pubmed search results 2008;Molecular Sequence Data;Membrane Proteins;Immunohistochemistry}, Month = {4}, Nlm_Id = {8809320}, Number = {2}, Organization = {Program in Developmental Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.}, Pages = {219-32}, Pii = {S0896-6273(05)00237-0}, Pubmed = {15848801}, Title = {Mutations in Drosophila sec15 reveal a function in neuronal targeting for a subset of exocyst components}, Uuid = {B66795D8-162A-45CA-BB67-F4D5377536D0}, Volume = {46}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.02.029}} @article{Meikle:2007, Abstract = {Tuberous sclerosis (TSC) is a hamartoma syndrome caused by mutations in TSC1 or TSC2 in which cerebral cortical tubers and seizures are major clinical issues. We have engineered mice in which most cortical neurons lose Tsc1 expression during embryonic development. These Tsc1 mutant mice display several neurological abnormalities beginning at postnatal day 5 with subsequent failure to thrive and median survival of 35 d. The mice also display clinical and electrographic seizures both spontaneously and with physical stimulation, and some seizures end in a fatal tonic phase. Many cortical and hippocampal neurons are enlarged and/or dysplastic in the Tsc1 mutant mice, strongly express phospho-S6, and are ectopic in multiple sites in the cortex and hippocampus. There is a striking delay in myelination in the mutant mice, which appears to be caused by an inductive neuronal defect. This new TSC brain model replicates several features of human TSC brain lesions and implicates an important function of Tsc1/Tsc2 in neuronal development.}, Author = {Meikle, Lynsey and Talos, Delia M. and Onda, Hiroaki and Pollizzi, Kristen and Rotenberg, Alexander and Sahin, Mustafa and Jensen, Frances E. and Kwiatkowski, David J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;Animals;Seizures;comparative study;Tuberous Sclerosis;Female;Mice, Transgenic;Mice, Inbred C57BL;research support, non-u.s. gov't;Disease Models, Animal;Male;Mice, Inbred CBA;Survival Rate;10 genetics malformation;Neurons;research support, n.i.h., extramural;Mice;Tumor Suppressor Proteins;24 Pubmed search results 2008;Demyelinating Diseases}, Month = {5}, Nlm_Id = {8102140}, Number = {21}, Organization = {Division of Translational Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.}, Pages = {5546-58}, Pii = {27/21/5546}, Pubmed = {17522300}, Title = {A mouse model of tuberous sclerosis: neuronal loss of Tsc1 causes dysplastic and ectopic neurons, reduced myelination, seizure activity, and limited survival}, Uuid = {C191DE96-E574-48C5-9CD7-E609857BA655}, Volume = {27}, Year = {2007}, url = {papers/Meikle_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5540-06.2007}} @article{Mekel-Bobrov:2005, Abstract = {The gene ASPM (abnormal spindle-like microcephaly associated) is a specific regulator of brain size, and its evolution in the lineage leading to Homo sapiens was driven by strong positive selection. Here, we show that one genetic variant of ASPM in humans arose merely about 5800 years ago and has since swept to high frequency under strong positive selection. These findings, especially the remarkably young age of the positively selected variant, suggest that the human brain is still undergoing rapid adaptive evolution.}, Author = {Mekel-Bobrov, Nitzan and Gilbert, Sandra L. and Evans, Patrick D. and Vallender, Eric J. and Anderson, Jeffrey R. and Hudson, Richard R. and Tishkoff, Sarah A. and Lahn, Bruce T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Sequence Analysis, DNA;10 Development;Animals;Adaptation, Biological;Humans;Research Support, U.S. Gov't, Non-P.H.S.;Brain;Pan troglodytes;Phylogeny;Models, Genetic;Gene Conversion;19 Neocortical evolution;Time;Haplotypes;Polymorphism, Genetic;Evolution;African Continental Ancestry Group;Gene Frequency;Recombination, Genetic;Asian Continental Ancestry Group;Genotype;Organ Size;Linkage Disequilibrium;Nerve Tissue Proteins;European Continental Ancestry Group;Selection (Genetics);Research Support, Non-U.S. Gov't}, Month = {9}, Nlm_Id = {0404511}, Number = {5741}, Organization = {Howard Hughes Medical Institute, Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.}, Pages = {1720-2}, Pii = {309/5741/1720}, Pubmed = {16151010}, Title = {Ongoing adaptive evolution of ASPM, a brain size determinant in Homo sapiens}, Uuid = {4371E42B-804D-40F6-BF83-1114EB210557}, Volume = {309}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1116815}} @article{Melamed:2008, Abstract = {The synchronous oscillatory activity characterizing many neurons in a network is often considered to be a mechanism for representing, binding, conveying, and organizing information. A number of models have been proposed to explain high-frequency oscillations, but the mechanisms that underlie slow oscillations are still unclear. Here, we show by means of analytical solutions and simulations that facilitating excitatory (E(f)) synapses onto interneurons in a neural network play a fundamental role, not only in shaping the frequency of slow oscillations, but also in determining the form of the up and down states observed in electrophysiological measurements. Short time constants and strong E(f) synapse-connectivity were found to induce rapid alternations between up and down states, whereas long time constants and weak E(f) synapse connectivity prolonged the time between up states and increased the up state duration. These results suggest a novel role for facilitating excitatory synapses onto interneurons in controlling the form and frequency of slow oscillations in neuronal circuits.}, Author = {Melamed, Ofer and Barak, Omri and Silberberg, Gilad and Markram, Henry and Tsodyks, Misha}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1573-6873}, Journal = {J Comput Neurosci}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9439510}, Number = {2}, Organization = {Department of Sciences, Holon Institute of Technology, Holon, 58102, Israel. ofer.melamed\@hit.ac.il}, Pages = {308-16}, Pubmed = {18483841}, Title = {Slow oscillations in neural networks with facilitating synapses}, Uuid = {D2AFCAF4-6FBD-4920-8375-AA7BD35FF5C6}, Volume = {25}, Year = {2008}, url = {papers/Melamed_JComputNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s10827-008-0080-z}} @article{Meletis:2006, Abstract = {There is increasing evidence that tumors are heterogeneous and that a subset of cells act as cancer stem cells. Several proto-oncogenes and tumor suppressors control key aspects of stem cell function, suggesting that similar mechanisms control normal and cancer stem cell properties. We show here that the prototypical tumor suppressor p53, which plays an important role in brain tumor initiation and growth, is expressed in the neural stem cell lineage in the adult brain. p53 negatively regulates proliferation and survival, and thereby self-renewal, of neural stem cells. Analysis of the neural stem cell transcriptome identified the dysregulation of several cell cycle regulators in the absence of p53, most notably a pronounced downregulation of p21 expression. These data implicate p53 as a suppressor of tissue and cancer stem cell self-renewal.}, Author = {Meletis, Konstantinos and Wirta, Valtteri and Hede, Sanna-Maria M. and Nist{\'e}r, Monica and Lundeberg, Joakim and Fris{\'e}n, Jonas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {03 Adult neurogenesis progenitor source;22 Stem cells;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8701744}, Number = {2}, Organization = {Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.}, Pages = {363-9}, Pii = {133/2/363}, Pubmed = {16368933}, Title = {p53 suppresses the self-renewal of adult neural stem cells}, Uuid = {FF1EBD28-0472-4C97-AD6B-79CB678D4769}, Volume = {133}, Year = {2006}, url = {papers/Meletis_Development2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.02208}} @article{Mellem:2008, Abstract = {Small, high-impedance neurons with short processes, similar to those found in the soil nematode Caenorhabditis elegans, are predicted to transmit electrical signals by passive propagation. However, we have found that certain neurons in C. elegans fire regenerative action potentials. These neurons resembled Schmitt triggers, as their potential state appears to be bistable. Transitions between up and down states could be triggered by application of the neurotransmitter glutamate or brief current pulses.}, Author = {Mellem, Jerry E. and Brockie, Penelope J. and Madsen, David M. and Maricq, Andres V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1546-1726}, Journal = {Nat Neurosci}, Keywords = {Electric Stimulation;Animals;Glutamic Acid;Caenorhabditis elegans;Feedback;Neural Conduction;Ions;Patch-Clamp Techniques;Animals, Genetically Modified;Receptors, AMPA;Calcium;Ion Channels;Green Fluorescent Proteins;Action Potentials;Neurons;Sodium;research support, n.i.h., extramural;Caenorhabditis elegans Proteins;24 Pubmed search results 2008;Stimulation, Chemical}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Department of Biology, University of Utah, Salt Lake City, Utah 84112-0840, USA.}, Pages = {865-7}, Pii = {nn.2131}, Pubmed = {18587393}, Title = {Action potentials contribute to neuronal signaling in C. elegans}, Uuid = {7DAB9696-4051-472E-9BBE-365B01E21C8D}, Volume = {11}, Year = {2008}, url = {papers/Mellem_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2131}} @article{Mellitzer:2000, Abstract = {Eph receptor tyrosine kinases and ephrins mediate contact-dependent cell interactions that regulate the repulsion and adhesion mechanisms involved in the guidance and assembly of cells. Recent work has revealed a role of overlapping Eph receptor and ephrin expression in modulating neuronal growth cone repulsion, and has shown that bidirectional activation restricts intermingling and communication between cell populations. In addition, progress has been made in understanding how Eph receptors and ephrins control cell adhesion.}, Author = {Mellitzer, G. and Xu, Q. and Wilkinson, D. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Receptor Protein-Tyrosine Kinases;24 Pubmed search results 2008;Ephrin-A1;10 Development;research support, non-u.s. gov't;Receptors, Eph Family;Cell Communication;Ephrin-B1;Membrane Proteins;Signal Transduction;10 circuit formation;Animals;Receptor, EphB4;Proteins;review;Neurons}, Month = {6}, Nlm_Id = {9111376}, Number = {3}, Organization = {Division of Developmental Neurobiology, National Institute for Medical Research, Mill Hill, NW7 1AA, UK.}, Pages = {400-8}, Pii = {S0959-4388(00)00095-7}, Pubmed = {10851175}, Title = {Control of cell behaviour by signalling through Eph receptors and ephrins}, Uuid = {B074347E-572F-46CB-BC03-931C0F2C0684}, Volume = {10}, Year = {2000}} @article{Mellitzer:1999, Abstract = {Eph proteins are receptors with tyrosine-kinase activity which, with their ephrin ligands, mediate contact-dependent cell interactions that are implicated in the repulsion mechanisms that guide migrating cells and neuronal growth cones to specific destinations. Ephrin-B proteins have conserved cytoplasmic tyrosine residues that are phosphorylated upon interaction with an EphB receptor, and may transduce signals that regulate a cellular response. Because Eph receptors and ephrins have complementary expression in many tissues during embryogenesis, bidirectional activation of Eph receptors and ephrin-B proteins could occur at interfaces of their expression domains, for example at segment boundaries in the vertebrate hindbrain. Previous work has implicated Eph receptors and ephrin-B proteins in the restriction of cell intermingling between hindbrain segments. We therefore analysed whether complementary expression of Eph receptors and ephrins restricts cell intermingling, and whether this requires bidirectional or unidirectional signalling. Here we report that bidirectional but not unidirectional signalling restricts the intermingling of adjacent cell populations, whereas unidirectional activation is sufficient to restrict cell communication through gap junctions. These results reveal that Eph receptors and ephrins regulate two aspects of cell behaviour that can stabilize a distinct identity of adjacent cell populations. 0028-0836 Journal Article}, Author = {Mellitzer, G. and Xu, Q. and Wilkinson, D. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Nature}, Keywords = {10 Development;Binding Sites;Signal Transduction;Gap Junctions/metabolism;In Vitro;Animals;Phosphorylation;Rhombencephalon/cytology/metabolism;Ephrin-B2;Fetal Proteins/*metabolism;Membrane Proteins/*metabolism;Receptor Protein-Tyrosine Kinases/*metabolism;F both;Support, Non-U.S. Gov't;Receptor, EphA4;Receptor, EphB2;Zebrafish;Ephrin-B1;*Cell Communication; Cooperative Behavior; Competitive Behavior; cell interaction; evolutionary dynamics}, Number = {6739}, Organization = {Division of Developmental Neurobiology, National Institute for Medical Research, London, UK.}, Pages = {77-81}, Pubmed = {10403252}, Title = {Eph receptors and ephrins restrict cell intermingling and communication}, Uuid = {3328C473-8108-4BE2-8BCE-3DCBB114E915}, Volume = {400}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10403252}} @article{Menezes:1998, Abstract = {The anterior subventricular zone (SVZa) is the site for postnatal neurogenesis of interneurons of the olfactory bulb (OB). Concurrently or after proliferation, neuronal precursors therein migrate within it to reach the OB, an event known as the rostral migratory stream (RMS). We used bromodeoxyuridine (BrdU) incorporation with short survival times to investigate the distribution of S-phase nuclei in the SVZa/RMS of the postnatal mouse. We observed that they were distributed along a radial, outside-in, decreasing gradient that persisted until postnatal day 10 (P10), then faded away to finally disappear by P16. After longer post-injection survival times labeled cell distribution became homogeneous. GFAP-positive glia are present at the periphery but not at the core of the SVZa. Our results represent the first evidence of a discrete spatial organization of a cell cycle phase within the SVZ, and also suggests a segregation of proliferating and migrating cells in the rostral migratory stream of the early postnatal mouse.}, Author = {Menezes, J. R. and Dias, F. and Garson, A. V. and Lent, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Anat Embryol (Berl)}, Keywords = {Neuroglia/cytology/metabolism;Glial Fibrillary Acidic Protein/metabolism;BB;Cerebral Ventricles/*cytology/growth &development;Animal;02 Adult neurogenesis migration;03 Adult neurogenesis progenitor source;Bromodeoxyuridine/metabolism;Support, Non-U.S. Gov't;Cell Division/physiology;Animals, Newborn;Olfactory Bulb/cytology/growth &development;Interneurons/cytology;Mice;Cell Movement/physiology;Immunohistochemistry;Prosencephalon/*cytology/growth &development;S Phase/*physiology}, Number = {3}, Organization = {Departamento de Anatomia, Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Brazil. jmenezes\@anato.ufrj.br}, Pages = {205-11.}, Title = {Restricted distribution of S-phase cells in the anterior subventricular zone of the postnatal mouse forebrain}, Uuid = {F6BD7F45-162C-4C6D-89B7-1E4A93A728EB}, Volume = {198}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9764975}} @article{Menezes:1995, Abstract = {In the mammalian forebrain most neurons originate from proliferating cells in the ventricular zone lining the lateral ventricles. These neurons become postmitotic before they undergo migration to their final destinations. In this study we examined the proliferative and migratory properties of cells destined for the olfactory bulb that arise postnatally from progenitor cells situated at the anterior extent of the subventricular zone (SVZa). The SVZa-derived cells migrate along a stereotypical pathway to the olfactory bulb where they become interneurons. Using lineage tracers and the cell proliferation marker BrdU, we have demonstrated that SVZa-derived cells in the rat retain the capacity for division after migrating away from their initial site of generation. These cells also express a neuron-specific tubulin, recognized by the antibody TuJ1. These results suggest that, unlike other immature neurons, these SVZa-derived cells have made a commitment to become neurons before becoming postmitotic.}, Author = {Menezes, J. R. and Smith, C. M. and Nelson, K. C. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {Olfactory Bulb/cytology/physiology;Cell Differentiation;Recombinant Proteins/analysis/biosynthesis;Neurons/*cytology/physiology;Transfection;Rats;Mitosis;Animal;Cell Movement;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Interneurons/cytology/physiology;03 Adult neurogenesis progenitor source;Animals, Newborn;beta-Galactosidase/analysis/biosynthesis;BB abstr;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Stem Cells/*cytology/physiology;Cell Division;Prosencephalon/*cytology/physiology;Immunohistochemistry}, Number = {6}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.}, Pages = {496-508.}, Title = {The division of neuronal progenitor cells during migration in the neonatal mammalian forebrain}, Uuid = {2DE28CFB-95CC-4488-AA25-39EB693E9321}, Volume = {6}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8742267}} @article{Menn:2006, Abstract = {Glial fibrillary acidic protein (GFAP)-positive astrocytes (type B cells) in the subventricular zone (SVZ) generate large numbers of new neurons in the adult brain. SVZ stem cells can also generate oligodendrocytes in vitro, but it is not known whether these adult primary progenitors generate oligodendrocytes in vivo. Myelin repair and oligodendrocyte formation in the adult brain is instead associated with glial-restricted progenitors cells, known as oligodendrocyte progenitor cells (OPCs). Here we show that type B cells also generate a small number of nonmyelinating NG2-positive OPCs and mature myelinating oligodendrocytes. Some type B cells and a small subpopulation of actively dividing type C (transit-amplifying) cells expressed oligodendrocyte lineage transcription factor 2 (Olig2), suggesting that oligodendrocyte differentiation in the SVZ begins early in the lineage. Olig2-positive, polysialylated neural cell adhesion molecule-positive, PDGF receptor alpha-positive, and beta-tubulin-negative cells originating in the SVZ migrated into corpus callosum, striatum, and fimbria fornix to differentiate into the NG2-positive nonmyelinating and mature myelinating oligodendrocytes. Furthermore, primary clonal cultures of type B cells gave rise to oligodendrocytes alone or oligodendrocytes and neurons. Importantly, the number of oligodendrocytes derived from type B cells in vivo increased fourfold after a demyelinating lesion in corpus callosum, indicating that SVZ astrocytes participate in myelin repair in the adult brain. Our work identifies SVZ type B cells as progenitors of oligodendrocytes in normal and injured adult brain.}, Author = {Menn, B{\'e}n{\'e}dicte and Garcia-Verdugo, Jose Manuel and Yaschine, Cynthia and Gonzalez-Perez, Oscar and Rowitch, David and Alvarez-Buylla, Arturo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Aging;24 Pubmed search results 2008;Cell Differentiation;research support, n.i.h., extramural ;Basic Helix-Loop-Helix Transcription Factors;research support, non-u.s. gov't ;Nerve Tissue Proteins;Stem Cells;Animals;Brain;Cerebral Ventricles;Mice;Oligodendroglia}, Month = {7}, Nlm_Id = {8102140}, Number = {30}, Organization = {Department of Neurosurgery and Developmental and Stem Cell Biology Program, University of California at San Francisco, San Francisco, California 94143, USA.}, Pages = {7907-18}, Pii = {26/30/7907}, Pubmed = {16870736}, Title = {Origin of oligodendrocytes in the subventricular zone of the adult brain}, Uuid = {FFCE7325-9713-4024-9DF9-1E1A32FA2D93}, Volume = {26}, Year = {2006}, url = {papers/Menn_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1299-06.2006}} @article{Mercier:2002, Abstract = {Cytogenesis in adult peripheral organs, and in all organs during development, occurs nearby basal laminae (BL) overlying connective tissue. Paradoxically, cytogenesis in the adult brain occurs primarily in the subependymal layer (SEL), a zone where no particular organization of BL and connective tissue has been described. We have reinvestigated the anatomy of the area considered the most neurogenic in the adult brain, the SEL of the lateral ventricle, in zones adjacent to the caudate putamen, corpus callosum, and lateral septal nucleus. Here, we report structural (confocal microscopy using laminin as a marker) and ultrastructural evidence for highly organized extravascular BL, unique to the SEL. The extravascular BL, termed fractones because of their fractal organization, were regularly arranged along the SEL and consisted of stems terminating in bulbs immediately underneath the ependyma. Fractones contacted local blood vessels by means of their stems. An individual fractone engulfed in its folds numerous processes of astrocytes, ependymocytes, microglial cells, and precursor cell types. The attachment site (base) of stems to blood vessels was extensively folded, overlying large perivascular macrophages that belong to a fibroblast/macrophage network coursing in the perivascular layer and through the meninges. In addition, collagen-1, which is associated with BL and growth factors during developmental morphogenetic inductions, was immunodetected in the SEL and particularly regionalized within fractones. Because macrophages and fibroblasts produce cytokines and growth factors that may concentrate in and exert their effect from the BL, we suggest that the structure described is implicated in adult neurogenesis, gliogenesis, and angiogenesis.}, Author = {Mercier, Frederic and Kitasako, John T. and Hatton, Glenn I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Animals;Macrophages;Image Processing, Computer-Assisted;Rats;Microscopy, Confocal;Neuronal Plasticity;Brain;Fibroblasts;Rats, Sprague-Dawley;Male;Fractals;03 Adult neurogenesis progenitor source;Research Support, U.S. Gov't, P.H.S.;Nerve Net;Cerebral Ventricles;Collagen Type I;Immunohistochemistry;Microscopy, Electron;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {22198815}, Month = {9}, Nlm_Id = {0406041}, Number = {2}, Organization = {Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA. fmercier\@pop.ucr.edu}, Pages = {170-88}, Pubmed = {12209835}, Title = {Anatomy of the brain neurogenic zones revisited: fractones and the fibroblast/macrophage network}, Uuid = {A9017865-A677-4B1B-B3AD-050049E09EE7}, Volume = {451}, Year = {2002}, url = {papers/Mercier_JCompNeurol2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10342}} @article{Meredith:2007, Abstract = {Fragile X syndrome, caused by a mutation in the Fmr1 gene, is characterized by mental retardation. Several studies reported the absence of long-term potentiation (LTP) at neocortical synapses in Fmr1 knockout (FMR1-KO) mice, but underlying cellular mechanisms are unknown. We find that in the prefrontal cortex (PFC) of FMR1-KO mice, spike-timing-dependent LTP (tLTP) is not so much absent, but rather, the threshold for tLTP induction is increased. Calcium signaling in dendrites and spines is compromised. First, dendrites and spines more often fail to show calcium transients. Second, the activity of L-type calcium channels is absent in spines. tLTP could be restored by improving reliability and amplitude of calcium signaling by increasing neuronal activity. In FMR1-KO mice that were raised in enriched environments, tLTP was restored to WT levels. Our results show that mechanisms for synaptic plasticity are in place in the FMR1-KO mouse PFC, but require stronger neuronal activity to be triggered.}, Author = {Meredith, Rhiannon M. and Holmgren, Carl D. and Weidum, Meredith and Burnashev, Nail and Mansvelder, Huibert D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {in vitro;Calcium Channel Blockers;Electric Stimulation;Calcium Signaling;Animals;Nifedipine;Neuronal Plasticity;Patch-Clamp Techniques;Female;Dendritic Spines;Pyramidal Cells;Mice, Inbred C57BL;research support, non-u.s. gov't;Calcium;Time Factors;Male;Animals, Newborn;Action Potentials;Cerebral Cortex;21 Neurophysiology;Mice, Knockout;Environment;Fragile X Mental Retardation Protein;Mice;24 Pubmed search results 2008;Excitatory Postsynaptic Potentials}, Month = {5}, Nlm_Id = {8809320}, Number = {4}, Organization = {Department of Experimental Neurophysiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, De Boelelaan 1085, 1081 HV, Amsterdam, The Netherlands.}, Pages = {627-38}, Pii = {S0896-6273(07)00330-3}, Pubmed = {17521574}, Title = {Increased threshold for spike-timing-dependent plasticity is caused by unreliable calcium signaling in mice lacking fragile X gene FMR1}, Uuid = {B6524C1B-17F0-4CEF-B4E0-9C9A46CA3334}, Volume = {54}, Year = {2007}, url = {papers/Meredith_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.04.028}} @article{Mergliano:2003, Abstract = {Programmed cell death plays an essential role during Drosophila embryonic development. A stereotypic series of cellular changes occur during apoptosis, most of which are initiated by a caspase cascade that is triggered by a trio of proteins, RPR, HID and GRIM. The final step in apoptosis is engulfment of the cell corpse. To monitor cell engulfment in vivo, we developed a fluorogenic beta-galactosidase substrate that is cleaved by an endogenous, lysosomal beta-galactosidase activity. The pattern of cell engulfment in wild-type embryos correlated well with the known pattern of apoptosis. Surprisingly, the pattern of cell engulfment persisted in apoptosis-deficient embryos. We provide evidence for a caspase-independent engulfment process that affects the majority of cells expected to die in developing Drosophila embryos.}, Author = {Mergliano, Jaime and Minden, Jonathan S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Gene Expression Regulation, Developmental;Research Support, U.S. Gov't, P.H.S.;Acridine Orange;Fluorescent Dyes;Biological Markers;Drosophila melanogaster;Endocytosis;beta-Galactosidase;Cell Death;Animals;Caspases;24 Pubmed search results 2008;Transgenes}, Medline = {22934560}, Month = {12}, Nlm_Id = {8701744}, Number = {23}, Organization = {Department of Biological Sciences and Science and Technology Center for Light Microscope Imaging and Biotechnology, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA.}, Pages = {5779-89}, Pii = {dev.00824}, Pubmed = {14534140}, Title = {Caspase-independent cell engulfment mirrors cell death pattern in Drosophila embryos}, Uuid = {DBDC98DA-6824-4D3D-B505-84EFE2F9B74F}, Volume = {130}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.00824}} @article{Merkle:2006, Abstract = {Neural stem cells (NSCs) are primary progenitors that give rise to neurons and glia in the embryonic, neonatal and adult brain. In recent years, we have learned three important things about these cells. First, NSCs correspond to cells previously thought to be committed glial cells. Second, embryonic and adult NSCs are lineally related: they transform from neuroepithelial cells into radial glia, then into cells with astroglial characteristics. Third, NSCs divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. These advances challenge our traditional perceptions of glia and stem cells, and provide the foundation for understanding the molecular basis of mammalian NSC behavior.}, Author = {Merkle, Florian T. and Alvarez-Buylla, Arturo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0955-0674}, Journal = {Curr Opin Cell Biol}, Keywords = {Neurons;Transcription Factors;Cell Differentiation;research support, non-u.s. gov't;Central Nervous System;Gene Expression Regulation, Developmental;Neuroglia;24 Pubmed search results 2008;Stem Cells;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;Animals;Cell Movement;Humans;review;Cell Lineage}, Month = {12}, Nlm_Id = {8913428}, Number = {6}, Organization = {Department of Neurological Surgery and Program in Developmental and Stem Cell Biology, University of California, San Francisco, Box 0525, HSW 1201A, San Francisco, California 94143, USA.}, Pages = {704-9}, Pii = {S0955-0674(06)00153-0}, Pubmed = {17046226}, Title = {Neural stem cells in mammalian development}, Uuid = {2714E463-3C81-4E2D-9423-E6FC1B8F3C07}, Volume = {18}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ceb.2006.09.008}} @article{Merkle:2004, Abstract = {Neural stem cells with the characteristics of astrocytes persist in the subventricular zone (SVZ) of the juvenile and adult brain. These cells generate large numbers of new neurons that migrate through the rostral migratory stream to the olfactory bulb. The developmental origin of adult neural stem cells is not known. Here, we describe a lox-Cre-based technique to specifically and permanently label a restricted population of striatal radial glia in newborn mice. Within the first few days after labeling, these radial glial cells gave rise to neurons, oligodendrocytes, and astrocytes, including astrocytes in the SVZ. Remarkably, the rostral migratory stream contained labeled migratory neuroblasts at all ages examined, including 150-day-old mice. Labeling dividing cells with the S-phase marker BrdUrd showed that new neurons continue to be produced in the adult by precursors ultimately derived from radial glia. Furthermore, both radial glia in neonates and radial glia-derived cells in the adult lateral ventricular wall generated self-renewing, multipotent neurospheres. These results demonstrate that radial glial cells not only serve as progenitors for many neurons and glial cells soon after birth but also give rise to adult SVZ stem cells that continue to produce neurons throughout adult life. This study identifies and provides a method to genetically modify the lineage that links neonatal and adult neural stem cells.}, Author = {Merkle, Florian T. and Tramontin, Anthony D. and Garc{\'\i}a-Verdugo, Jos{\'e} Manuel and Alvarez-Buylla, Arturo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;03 Adult neurogenesis progenitor source}, Month = {12}, Nlm_Id = {7505876}, Number = {50}, Organization = {Department of Neurological Surgery, Developmental and Stem Cell Biology Program, Box 0525, University of California-San Francisco, San Francisco, CA 94143, USA.}, Pages = {17528-32}, Pii = {0407893101}, Pubmed = {15574494}, Title = {Radial glia give rise to adult neural stem cells in the subventricular zone}, Uuid = {7710F98A-68D7-11DA-A4B6-000D9346EC2A}, Volume = {101}, Year = {2004}, url = {papers/Merkle_ProcNatlAcadSciUSA2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0407893101}} @article{Mestres:1980, Abstract = {In order to analyse whether or not surface morphology and intracellular skeleton are interdependent, Cytochalasin B (CB), an agent which interferes with microfilaments, was introduced ino the brain ventricular system of adult rats. Following intraventricular application of CB for different periods of time (up to 6h) the animals were sacrificed and the ventricular wall examined with both transmission and scanning electron microscopes. The first signs of cellular alteration after short periods of CB application were an increase in the number of microfilaments within the cytoplasm and the appearance of a multitude of small knobs on the surface of the cilia of the cuboidal ependymal cells, whereas the tanycytes exhibited extensive blebbing at their apical poles. When the duration of CB perfusion was lengthened, entire ciliated cells became rounded up and were loosened from the epithelium, especially in the transition zone of the third ventricle where the ependyma is composed of both tanycytes and ciliated cells. The significance of the CB-induced changes in the ependyma are discussed in relation to the ependymal surface modifications seen under physiological and other experimental conditions. 0586-5581 Journal Article}, Author = {Mestres, P. and Garfia, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Scan Electron Microsc}, Keywords = {Cell Adhesion/drug effects;Biological Transport/drug effects;Rats;Microscopy, Electron, Scanning;08 Aberrant cell cycle;Cytochalasin B/*pharmacology;Hypothalamus/*drug effects;EE, G abstr;Ependyma/cytology/*drug effects;Cytoskeleton/drug effects;Animals;Male;Cell Membrane/ultrastructure;Cilia/ultrastructure}, Number = {3}, Pages = {465-74}, Pubmed = {7191139}, Title = {Effects of cytochalasin B on the ependyma}, Uuid = {2CBD9D02-1850-4ADC-8B72-4DB766E3CC25}, Year = {1980}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7191139}} @article{Metea:2006, Abstract = {Neuronal activity evokes localized changes in blood flow. Although this response, termed neurovascular coupling, is widely used to monitor human brain function and diagnose pathology, the cellular mechanisms that mediate the response remain unclear. We investigated the contribution of glial cells to neurovascular coupling in the acutely isolated mammalian retina. We found that light stimulation and glial cell stimulation can both evoke dilation or constriction of arterioles. Light-evoked and glial-evoked vasodilations were blocked by inhibitors of cytochrome P450 epoxygenase, the synthetic enzyme for epoxyeicosatrienoic acids. Vasoconstrictions, in contrast, were blocked by an inhibitor of omega-hydroxylase, which synthesizes 20-hydroxyeicosatetraenoic acid. Nitric oxide influenced whether vasodilations or vasoconstrictions were produced in response to light and glial stimulation. Light-evoked vasoactivity was blocked when neuron-to-glia signaling was interrupted by a purinergic antagonist. These results indicate that glial cells contribute to neurovascular coupling and suggest that regulation of blood flow may involve both vasodilating and vasoconstricting components.}, Author = {Metea, Monica R. and Newman, Eric A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8102140}, Number = {11}, Organization = {Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.}, Pages = {2862-70}, Pii = {26/11/2862}, Pubmed = {16540563}, Title = {Glial cells dilate and constrict blood vessels: a mechanism of neurovascular coupling}, Uuid = {2D3D3368-F8CE-48AC-9BB9-9BA6DED29897}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4048-05.2006}} @article{Metin:1996, Abstract = {In the nervous system of many species, growing axons associate transiently with cellular groupings along their path. Whether this mechanism applies to the development of corticothalamic and thalamocortical projections is unknown. Using carbocyanine dyes, we studied the early growth of both corticofugal and thalamocortical fibers in hamster embryos. At embryonic day 11.5 (E11.5), corticofugal fibers invade the lateral ganglionic eminence (LGE), and thalamocortical fibers invade the medial ganglionic eminence (MGE). At this age, both sets of fibers are not yet in contact with each other. At the same time, neurons in each subdivision of the GE grow toward the cortex and thalamus. During the next 24 hr, corticofugal and thalamocortical fibers remain within the confines of the GE, where they course at different radial levels and bear large and complex growth cones. In the LGE, corticofugal fibers are often found in close association with cells that are likely to be neuronal. Starting on E13.5, both early projections from the GE decrease, and corticothalamic and thalamocortical fibers invade their definitive target regions. To test whether the GE specifically orients the growth and trajectories of cortical fibers even in the absence of the reciprocal thalamic projection, we cocultured explants of cortex and GE from either hamster or mouse embryos. These experiments showed that the GE, but not other tested brain regions, is able specifically to orient the growth of cortical axons. We therefore suggest that the GE may be an intermediate target in the pathfinding of axons between the cortex and the thalamus. 0270-6474 Journal Article}, Author = {Metin, C. and Godement, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Neurosci}, Keywords = {Cerebral Cortex/*anatomy &histology;Axons/*physiology;Thalamus/*anatomy &histology;Immunohistochemistry;Neural Pathways/physiology;Mice, Inbred C57BL;N;Ganglia/*anatomy &histology;Support, Non-U.S. Gov't;Animals;Hamsters;Mice;19 Neocortical evolution}, Number = {10}, Organization = {Institut Alfred Fessard, Centre National de la Recherche Scientifique UPR 2212, Gif-sur-Yvette, France.}, Pages = {3219-35}, Pubmed = {8627360}, Title = {The ganglionic eminence may be an intermediate target for corticofugal and thalamocortical axons}, Uuid = {C888318E-EE6E-4C00-BD7E-6F5A10CEEB35}, Volume = {16}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8627360}} @article{Meucci:2000, Abstract = {Recent in vitro and in vivo studies have shown that the chemokine fractalkine is widely expressed in the brain and localized principally to neurons. Central nervous system expression of CX(3)CR1, the only known receptor for fractalkine, has been demonstrated exclusively on microglia and astrocytes. Thus, it has been proposed that fractalkine regulates cellular communication between neurons (that produce fractalkine) and microglia (that express its receptor). Here we show, for the first time, that hippocampal neurons also express CX(3)CR1. Receptor activation by soluble fractalkine induces activation of the protein kinase Akt, a major component of prosurvival signaling pathways, and nuclear translocation of NF-kappaB, a downstream effector of Akt. Fractalkine protects hippocampal neurons from the neurotoxicity induced by the HIV-1 envelope protein gp120(IIIB), an effect blocked by anti-CX(3)CR1 antibodies. Experiments with two different inhibitors of the phosphatidylinositol 3-kinase, a key enzyme in the activation of Akt, and with a phospholipid activator of Akt demonstrate that Akt activation is responsible for the neuroprotective effects of fractalkine. These data show that neuronal CX(3)CR1 receptors mediate the neurotrophic effects of fractalkine, suggesting that fractalkine and its receptor are involved in a complex network of both paracrine and autocrine interactions between neurons and glia.}, Author = {Meucci, O. and Fatatis, A. and Simen, A. A. and Miller, R. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Survival;Signal Transduction;Animals;Astrocytes;DNA-Binding Proteins;Rats;NF-kappa B;Phosphatidylinositols;Recombinant Proteins;Culture Techniques;Receptors, HIV;Hippocampus;Protein-Serine-Threonine Kinases;11 Glia;1-Phosphatidylinositol 3-Kinase;Chemokines, CX3C;Research Support, U.S. Gov't, P.H.S.;I-kappa B;Neurons;Chemokines, CXC;24 Pubmed search results 2008;Proto-Oncogene Proteins;Membrane Proteins;Receptors, Cytokine}, Medline = {20345114}, Month = {7}, Nlm_Id = {7505876}, Number = {14}, Organization = {Department of Neurobiology, Pharmacology, and Physiology, and Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.}, Pages = {8075-80}, Pii = {090017497}, Pubmed = {10869418}, Title = {Expression of CX3CR1 chemokine receptors on neurons and their role in neuronal survival}, Uuid = {2ACA9BFB-DA87-4C70-9115-EA9DF6C7A7E9}, Volume = {97}, Year = {2000}, url = {papers/Meucci_ProcNatlAcadSciUSA2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.090017497}} @article{Meuth:1974, Author = {Meuth, M. and Green, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {15 ERVs retroelements;Animals;24 Pubmed search results 2008;DNA;Deoxycytidine;Cell Survival;Cell Aggregation;15 Retrovirus mechanism;Cells, Cultured;Bromodeoxyuridine;Ribonucleotide Reductases;Bromouracil;Mice}, Medline = {75129340}, Month = {6}, Nlm_Id = {0413066}, Number = {2}, Pages = {109-12}, Pii = {0092-8674(74)90099-3}, Pubmed = {4477047}, Title = {Induction of a deoxycytidineless state in cultured mammalian cells by bromodeoxyuridine}, Uuid = {8DFFAC32-4328-11DB-A5D2-000D9346EC2A}, Volume = {2}, Year = {1974}} @article{Mey:2005, Abstract = {Retinoic acid (RA) promotes growth and differentiation in many developing tissues but less is known about its influence on CNS regeneration. We investigated the possible involvement of RA in rat spinal cord injury (SCI) using the New York University (NYU) impactor to induce mild or moderate spinal cord contusion injury. Changes in RA at the lesion site were determined by measuring the activity of the enzymes for its synthesis, the retinaldehyde dehydrogenases (RALDHs). A marked increase in enzyme activity occurred by day 4 and peaked at days 8-14 following the injuries. RALDH2 was the only detectable RALDH present in the control or injured spinal cord. The cellular localization of RALDH2 was identified by immunostaining. In the noninjured spinal cord, RALDH2 was detected in oligodendroglia positive for the markers RIP and CNPase. Expression was also intense in the arachnoid membrane surrounding the spinal cord. After SCI the increase in RALDH2 was independent of the RIP- and CNPase-positive cells, which were severely depleted. Instead, RALDH2 was present in a cell type not previously identified as capable of synthesizing RA, that expressed NG2 and that was negative for markers of astrocytes, oligodendroglia, microglia, neurons, Schwann cells and immature lymphocytes. We postulate that the RALDH2- and NG2-positive cells migrate into the injured sites from the adjacent arachnoid membrane, where the RALDH2-positive cells proliferate substantially following SCI. These findings indicate that close correlations exist between RA synthesis and SCI and that RA may play a role in the secondary events that follow acute SCI.}, Author = {Mey, J{\"o}rg and J Morassutti, Dante and Brook, Gary and Liu, Rong-Huan H. and Zhang, Yi-Ping P. and Koopmans, Guido and McCaffery, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;Spinal Cord Injuries;Comparative Study;Rats;Research Support, U.S. Gov't, P.H.S.;Aldehyde Oxidoreductases;Tretinoin;Antigens;Research Support, N.I.H., Extramural;11 Glia;Male;Proteoglycans;Animals}, Month = {3}, Nlm_Id = {8918110}, Number = {6}, Organization = {Institute of Biology II, RWTH Aachen, Germany.}, Pages = {1555-68}, Pii = {EJN3928}, Pubmed = {15845083}, Title = {Retinoic acid synthesis by a population of NG2-positive cells in the injured spinal cord}, Uuid = {39EC210E-C63C-4B45-BA3C-538AE5A74031}, Volume = {21}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2005.03928.x}} @article{Mezey:2003, Abstract = {Adult bone marrow stem cells seem to differentiate into muscle, skin, liver, lung, and neuronal cells in rodents and have been shown to regenerate myocardium, hepatocytes, and skin and gastrointestinal epithelium in humans. Because we have demonstrated previously that transplanted bone marrow cells can enter the brain of mice and differentiate into neurons there, we decided to examine postmortem brain samples from females who had received bone marrow transplants from male donors. The underlying diseases of the patients were lymphocytic leukemia and genetic deficiency of the immune system, and they survived between 1 and 9 months after transplant. We used a combination of immunocytochemistry (utilizing neuron-specific antibodies) and fluorescent in situ hybridization histochemistry to search for Y chromosome-positive cells. In all four patients studied we found cells containing Y chromosomes in several brain regions. Most of them were nonneuronal (endothelial cells and cells in the white matter), but neurons were certainly labeled, especially in the hippocampus and cerebral cortex. The youngest patient (2 years old), who also lived the longest time after transplantation, had the greatest number of donor-derived neurons (7 in 10,000). The distribution of the labeled cells was not homogeneous. There were clusters of Y-positive cells, suggesting that single progenitor cells underwent clonal expansion and differentiation. We conclude that adult human bone marrow cells can enter the brain and generate neurons just as rodent cells do. Perhaps this phenomenon could be exploited to prevent the development or progression of neurodegenerative diseases or to repair tissue damaged by infarction or trauma.}, Author = {Mezey, Eva and Key, Sharon and Vogelsang, Georgia and Szalayova, Ildiko and Lange, G. David and Crain, Barbara}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Microscopy, Confocal;In Situ Hybridization, Fluorescence;Cell Differentiation;Adult;Infant;Immunohistochemistry;Female;Bone Marrow Cells;Cell Division;Bone Marrow Transplantation;22 Stem cells;Microscopy, Fluorescence;Child;Male;Brain;Humans;Neurons}, Medline = {22457179}, Month = {2}, Nlm_Id = {7505876}, Number = {3}, Organization = {National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS)/In situ Hybridization Facility (ISHF), Bethesda, MD 20892, USA. mezey\@codon.nih.gov}, Pages = {1364-9}, Pii = {0336479100}, Pubmed = {12538864}, Title = {Transplanted bone marrow generates new neurons in human brains}, Uuid = {37E716AA-D3B2-11D9-A0E9-000D9346EC2A}, Volume = {100}, Year = {2003}, url = {papers/Mezey_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0336479100}} @article{Mezey:2000, Abstract = {Bone marrow stem cells give rise to a variety of hematopoietic lineages and repopulate the blood throughout adult life. We show that, in a strain of mice incapable of developing cells of the myeloid and lymphoid lineages, transplanted adult bone marrow cells migrated into the brain and differentiated into cells that expressed neuron-specific antigens. These findings raise the possibility that bone marrow-derived cells may provide an alternative source of neurons in patients with neurodegenerative diseases or central nervous system injury.}, Author = {Mezey, E. and Chandross, K. J. and Harta, G. and Maki, R. A. and McKercher, S. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Cell Differentiation;Animals;Stem Cell Transplantation;Bone Marrow Transplantation;Microscopy, Confocal;Immunoenzyme Techniques;Brain;Phosphopyruvate Hydratase;Female;Cell Movement;Male;Research Support, U.S. Gov't, P.H.S.;Antigens;Bone Marrow Cells;Mice, Knockout;Intermediate Filament Proteins;Neurons;Mice;Y Chromosome;Stem Cells;Biological Markers;Nerve Tissue Proteins}, Medline = {20553650}, Month = {12}, Nlm_Id = {0404511}, Number = {5497}, Organization = {Basic Neuroscience Program, Laboratory of Developmental Neurogenetics, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA. mezey\@codon.nih.gov}, Pages = {1779-82}, Pii = {9025}, Pubmed = {11099419}, Title = {Turning blood into brain: cells bearing neuronal antigens generated in vivo from bone marrow}, Uuid = {ED9BE605-99B6-4936-86D6-B08EF3B9C7BD}, Volume = {290}, Year = {2000}, url = {papers/Mezey_Science2000.pdf}} @article{Mi:2000, Abstract = {Many mammalian viruses have acquired genes from their hosts during their evolution. The rationale for these acquisitions is usually quite clear: the captured genes are subverted to provide a selective advantage to the virus. Here we describe the opposite situation, where a viral gene has been sequestered to serve an important function in the physiology of a mammalian host. This gene, encoding a protein that we have called syncytin, is the envelope gene of a recently identified human endogenous defective retrovirus, HERV-W. We find that the major sites of syncytin expression are placental syncytiotrophoblasts, multinucleated cells that originate from fetal trophoblasts. We show that expression of recombinant syncytin in a wide variety of cell types induces the formation of giant syncytia, and that fusion of a human trophoblastic cell line expressing endogenous syncytin can be inhibited by an anti-syncytin antiserum. Our data indicate that syncytin may mediate placental cytotrophoblast fusion in vivo, and thus may be important in human placental morphogenesis.}, Author = {Mi, S. and Lee, X. and Li, X. and Veldman, G. M. and Finnerty, H. and Racie, L. and LaVallie, E. and Tang, X. Y. and Edouard, P. and Howes, S. and Keith, J. C. and McCoy, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Interleukin-12;Gene Products, env;Tissue Distribution;Animals;Humans;Sequence Homology, Amino Acid;Transfection;15 Retrovirus mechanism;Cell Fusion;Trophoblasts;Endogenous Retroviruses;COS Cells;Giant Cells;Hela Cells;Green Fluorescent Proteins;Proviruses;Genes, Viral;Tumor Cells, Cultured;Pregnancy Proteins;24 Pubmed search results 2008;Amino Acid Sequence;Molecular Sequence Data;15 ERVs retroelements;Luminescent Proteins;Gene Expression}, Medline = {20155476}, Month = {2}, Nlm_Id = {0410462}, Number = {6771}, Organization = {Genetics Institute, Inc., Cambridge, Massachusetts 02140, USA.}, Pages = {785-9}, Pubmed = {10693809}, Title = {Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis}, Uuid = {A12D8DB6-EE4C-11DA-8605-000D9346EC2A}, Volume = {403}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35001608}} @article{Michaels:1988, Abstract = {The autopsied brains of three homosexual men with acquired immune deficiency syndrome (AIDS), progressive encephalopathy and widespread multinucleated giant cell encephalitis were investigated by lectin and immunohistochemical methods to ascertain the cellular distribution of a human immunodeficiency virus (HIV) core protein, p25. Abundant viral antigen was present in all brains, limited to perivascular macrophages, microglial and multinucleated cells, some bearing elongated cytoplasmic processes. The multinucleated cells were consistently labelled by the lectin Ricinus communis agglutinin-1, a marker for microglia, which demonstrated process-bearing variants of these cells. The prominent staining of microglia for viral antigen and the morphological suggestion that they fuse with other microglia and/or macrophages to form the multinucleated cells characteristic of HIV encephalitis indicate that microglia are probably direct targets of HIV infection and serve to propagate and amplify this retroviral encephalitis.}, Author = {Michaels, J. and Price, R. W. and Rosenblum, M. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Ricin;Neuroglia;Research Support, Non-U.S. Gov't;Aged;Encephalitis;Adult;Research Support, U.S. Gov't, P.H.S.;HIV Antigens;Viral Core Proteins;Middle Aged;Homosexuality;Acquired Immunodeficiency Syndrome;11 Glia;Humans;Male;HIV}, Medline = {89021907}, Nlm_Id = {0412041}, Number = {4}, Organization = {Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.}, Pages = {373-9}, Pubmed = {3176903}, Title = {Microglia in the giant cell encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion}, Uuid = {F0C6C354-2299-4372-85CF-9CEA7B7B48B6}, Volume = {76}, Year = {1988}} @article{Migheli:1999, Abstract = {A missense mutation in the gene coding for the G-protein-activated inwardly rectifying potassium (GIRK) channel, GIRK2, is responsible for apoptosis in the external germinal layer (EGL) of the cerebellum and a nonapoptotic death of midbrain dopaminergic neurons in the weaver (wv) mouse. Failure of axonogenesis and migration are considered to be the primary consequences of GIRK2 channel malfunction in the cerebellum. We investigated whether a disruption of the cell cycle precedes the failure of migration and axonogenesis and leads to massive apoptosis. To this end, immunohistochemistry and immunoblotting for PCNA, Cdk4, cyclin D, cyclin A, and the Cdk inhibitor p27/kip1, as well as in situ end-labeling for apoptotic DNA fragmentation, were applied to cerebella of P7-P21+/+, wv/+, and wv/wv mice. In +/+ and wv/+ mice, the expression of cell cycle proteins was limited to the outer, premigratory zone of the EGL. Antibodies to p27, a marker of cell differentiation, gave a reverse staining pattern. Due to migration delay, patches of p27-positive cells persisted in the outer EGL in P21 wv/+ mice. On the contrary, marked cell cycle up-regulation and absence of p27 occurred throughout the EGL at all ages in wv/wv mice, indicating an inability to switch off the cell cycle. Mitotic index evaluation showed that cell cycle activation was unrelated to proliferative events. Cell cycle proteins were not expressed in the substantia nigra, suggesting that nonapoptotic death of mature dopaminergic neurons is not preceded by abortive cell cycle re-entry. Our data show that abnormalities of the cell cycle in wv/wv cerebellum represent a major and early consequence of GIRK2 channel malfunction and may strongly influence the susceptibility of EGL cells to apoptosis. These observations may help in understanding the pathogenesis of human neurological channelopathies. 0002-9440 Journal Article}, Author = {Migheli, A. and Piva, R. and Casolino, S. and Atzori, C. and Dlouhy, S. R. and Ghetti, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {Am J Pathol}, Keywords = {Potassium Channels/metabolism;Human;Animals;Cyclins/analysis/*metabolism;Ion Channels/physiology;*Cell Cycle Proteins;Mitosis;EE pdf;*Tumor Suppressor Proteins;Cyclin-Dependent Kinases/analysis/antagonists &inhibitors/*metabolism;08 Aberrant cell cycle;Substantia Nigra/anatomy &histology/physiology;Microtubule-Associated Proteins/analysis/*metabolism;*Mice, Neurologic Mutants;In Situ Hybridization;Support, Non-U.S. Gov't;*Apoptosis;*Cell Cycle;Mitotic Index;DNA Damage;Genotype;Support, U.S. Gov't, P.H.S.;Mice;Immunohistochemistry;Proliferating Cell Nuclear Antigen/*analysis/*metabolism;Cerebellum/*metabolism/*physiology;DNA Fragmentation;Cyclin A/analysis/*metabolism}, Number = {2}, Organization = {Department of Neuroscience, Laboratory of Neuropathology, University of Turin, Italy.}, Pages = {365-73}, Title = {A cell cycle alteration precedes apoptosis of granule cell precursors in the weaver mouse cerebellum}, Uuid = {77F51F59-226A-43C8-B65D-88D45D67BC23}, Volume = {155}, Year = {1999}, url = {papers/Migheli_AmJPathol1999.pdf}} @article{Migliore:2006, Abstract = {The NEURON simulation environment has been extended to support parallel network simulations. Each processor integrates the equations for its subnet over an interval equal to the minimum (interprocessor) presynaptic spike generation to postsynaptic spike delivery connection delay. The performance of three published network models with very different spike patterns exhibits superlinear speedup on Beowulf clusters and demonstrates that spike communication overhead is often less than the benefit of an increased fraction of the entire problem fitting into high speed cache. On the EPFL IBM Blue Gene, almost linear speedup was obtained up to 100 processors. Increasing one model from 500 to 40,000 realistic cells exhibited almost linear speedup on 2,000 processors, with an integration time of 9.8 seconds and communication time of 1.3 seconds. The potential for speed-ups of several orders of magnitude makes practical the running of large network simulations that could otherwise not be explored.}, Author = {Migliore, M. and Cannia, C. and Lytton, W. W. and Markram, Henry and Hines, M. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0929-5313}, Journal = {J Comput Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {9439510}, Number = {2}, Organization = {Institute of Biophysics, National Research Council, via U La Malfa 153, 90146, Palermo, Italy. michele.migliore\@pa.ibf.cnr.it}, Pages = {119-29}, Pubmed = {16732488}, Title = {Parallel network simulations with NEURON}, Uuid = {ED48959B-C447-42A4-9707-63A2806F764A}, Volume = {21}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s10827-006-7949-5}} @article{Migliore:2007, Abstract = {Lateral inhibition of cells surrounding an excited area is a key property of sensory systems, sharpening the preferential tuning of individual cells in the presence of closely related input signals. In the olfactory pathway, a dendrodendritic synaptic microcircuit between mitral and granule cells in the olfactory bulb has been proposed to mediate this type of interaction through granule cell inhibition of surrounding mitral cells. However, it is becoming evident that odor inputs result in broad activation of the olfactory bulb with interactions that go beyond neighboring cells. Using a realistic modeling approach we show how backpropagating action potentials in the long lateral dendrites of mitral cells, together with granule cell actions on mitral cells within narrow columns forming glomerular units, can provide a mechanism to activate strong local inhibition between arbitrarily distant mitral cells. The simulations predict a new role for the dendrodendritic synapses in the multicolumnar organization of the granule cells. This new paradigm gives insight into the functional significance of the patterns of connectivity revealed by recent viral tracing studies. Together they suggest a functional wiring of the olfactory bulb that could greatly expand the computational roles of the mitral-granule cell network.}, Author = {Migliore, and Shepherd,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0929-5313}, Journal = {J Comput Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {9439510}, Organization = {Department of Neurobiology, Yale University School of Medicine, New Haven, CT, USA.}, Pubmed = {17674173}, Title = {Dendritic action potentials connect distributed dendrodendritic microcircuits}, Uuid = {14F43D0B-19B5-4AC6-ABBF-C7A20841DDB6}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s10827-007-0051-9}} @article{Mignone:2004, Abstract = {Neural stem cells generate a wide spectrum of cell types in developing and adult nervous systems. These cells are marked by expression of the intermediate filament nestin. We used the regulatory elements of the nestin gene to generate transgenic mice in which neural stem cells of the embryonic and adult brain are marked by the expression of green fluorescent protein (GFP). We used these animals as a reporter line for studying neural stem and progenitor cells in the developing and adult nervous systems. In these nestin-GFP animals, we found that GFP-positive cells reflect the distribution of nestin-positive cells and accurately mark the neurogenic areas of the adult brain. Nestin-GFP cells can be isolated with high purity by using fluorescent-activated cell sorting and can generate multipotential neurospheres. In the adult brain, nestin-GFP cells are approximately 1,400-fold more efficient in generating neurospheres than are GFP-negative cells and, despite their small number, give rise to 70 times more neurospheres than does the GFP-negative population. We characterized the expression of a panel of differentiation markers in GFP-positive cells in the nestin-GFP transgenics and found that these cells can be divided into two groups based on the strength of their GFP signal: GFP-bright cells express glial fibrillary acidic protein (GFAP) but not betaIII-tubulin, whereas GFP-dim cells express betaIII-tubulin but not GFAP. These two classes of cells represent distinct classes of neuronal precursors in the adult mammalian brain, and may reflect different stages of neuronal differentiation. We also found unusual features of nestin-GFP-positive cells in the subgranular cell layer of the dentate gyrus. Together, our results indicate that GFP-positive cells in our transgenic animals accurately represent neural stem and progenitor cells and suggest that these nestin-GFP-expressing cells encompass the majority of the neural stem cells in the adult brain.}, Author = {Mignone, John L. and Kukekov, Valery and Chiang, Ann-Shyn S. and Steindler, Dennis and Enikolopov, Grigori}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Green Fluorescent Proteins;Immunohistochemistry;Luminescent Proteins;Animals;Cells, Cultured;Brain;Flow Cytometry;Hippocampus;Gene Expression Regulation, Developmental;Research Support, U.S. Gov't, P.H.S.;Stem Cell Transplantation;Proteins;Cell Count;Intermediate Filament Proteins;Bromodeoxyuridine;Tubulin;11 Glia;Comparative Study;Glial Fibrillary Acidic Protein;Time Factors;Embryo;Stem Cells;Indicators and Reagents;Microscopy, Confocal;Mice;Research Support, Non-U.S. Gov't;Neurons;Mice, Transgenic;Reverse Transcriptase Polymerase Chain Reaction;Nerve Tissue Proteins}, Month = {2}, Nlm_Id = {0406041}, Number = {3}, Organization = {Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.}, Pages = {311-24}, Pubmed = {14730584}, Title = {Neural stem and progenitor cells in nestin-GFP transgenic mice}, Uuid = {6A7851D4-B1E3-41B4-978F-762F33AF7919}, Volume = {469}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10964}} @article{Mikhailov:1998, Abstract = {Microtubules (MTs) contribute to the directional locomotion of many cell types through an unknown mechanism. Previously, we showed that low concentrations (<200 nM) of nocodazole or taxol reduced the rate of locomotion of NRK fibroblasts over 60\%without altering MT polymer level [Liao et al., 1995: J. Cell Sci. 108:3473-3483]. In this paper, we directly measured the dynamics of MTs in migrating NRK cells injected with rhodamine tubulin and treated with low concentrations of nocodazole or taxol. Both drug treatments caused statistically significant reductions (approx. twofold) in growth and shortening rates and less dramatic effects on rescue and catastrophe transition frequencies. The percent time MTs were inactive (i.e., paused) increased greater than twofold in nocodazole- and taxol-treated cells, while the percent time growing was substantially reduced. Three parameters of MT dynamics were linearly related to the rates of locomotion determined previously: rate of shortening, percent time pausing and percent time growing. The number of MTs that came within 1 microm of the leading edge was reduced in drug-treated cells, suggesting that reduced MT dynamics may affect actin arrays necessary for cell locomotion. We examined two such structures, lamellipodium and adhesion plaques, and found that lamellipodia area was coordinately reduced with MT dynamics. No effect was detected on adhesion plaque density or distribution. In time-lapse recordings, MTs did not penetrate into the lamellipodium of untreated cells, suggesting that MTs affect lamellipodia either through their interaction with factors at the base of the lamellipodium or by releasing factors that diffuse into the lamellipodia. In support of the latter hypothesis, when all MTs were rapidly depolymerized by 20 microM nocodazole, we detected the rapid formation of exaggerated protrusions from the leading edge of the cell. Our results show for the first time a linear relationship between MT dynamics and the formation of the lamellipodium and support the idea that MT dynamics may contribute to cell locomotion by regulating the size of the lamellipodium, perhaps through diffusable factors. 0886-1544 Journal Article}, Author = {Mikhailov, A. and Gundersen, G. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {Cell Motil Cytoskeleton}, Keywords = {Cell Movement/drug effects/physiology;EE, T abstr;EE, T pdf;Paclitaxel/*pharmacology;Image Processing, Computer-Assisted;Cell Adhesion;Cell Line;08 Aberrant cell cycle;Dose-Response Relationship, Drug;Tyrosine;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't;Microtubules/drug effects/*physiology;Nocodazole/*pharmacology}, Number = {4}, Organization = {Department of Pathology, Columbia University, New York, New York 10032, USA.}, Pages = {325-40}, Pubmed = {9858157}, Title = {Relationship between microtubule dynamics and lamellipodium formation revealed by direct imaging of microtubules in cells treated with nocodazole or taxol}, Uuid = {922E92A0-243A-43D8-8363-D4394451C121}, Volume = {41}, Year = {1998}, url = {papers/Mikhailov_CellMotilCytoskeleton1998}} @article{Mikita:1988, Abstract = {Cytosine arabinoside (araC) is a potent antileukemic agent that is misincorporated into DNA in the course of its action. We have developed a chemical synthetic method that allows site-specific introduction of araC into synthetic DNA oligomers. We describe here the utilization of these oligomers as primer/template substrates for in vitro DNA synthesis reactions and as fragments for DNA ligation. These studies were undertaken to investigate the manner in which sites of araC misincorporation constitute sites of DNA dysfunction. AraCMP at the primer terminus dramatically reduced the rate of next nucleotide addition for Escherichia coli polymerase I (Klenow fragment) (Pol I), T4 polymerase, HeLa cell polymerase alpha 2 (Pol alpha 2), and AMV reverse transcriptase. Polymerases with associated 3'-5'exonuclease activity preferentially excised araCMP from the primer terminus prior to chain elongation. AraCMP-terminated fragments were ligated more slowly than control fragments by T4 DNA ligase. AraCMP located at an internucleotide site in the template markedly slowed replicative bypass for Pol I, T4 polymerase, and Pol alpha 2, but not for reverse transcriptase. Synthesis was partially arrested after insertion of the correct nucleotide opposite the lesion site. These results suggest a complex mechanism for the inhibition of DNA replication by araC when it is misincorporated into DNA. 0006-2960 Journal Article}, Author = {Mikita, T. and Beardsley, G. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Biochemistry}, Keywords = {Base Sequence;RNA-Directed DNA Polymerase/metabolism;*DNA Damage;Human;DNA Polymerase II/metabolism;08 Aberrant cell cycle;DNA Polymerase I/metabolism;Hela Cells/enzymology;EE abstr;DNA-Directed DNA Polymerase/*metabolism;Escherichia coli/enzymology;Oligodeoxyribonucleotides/chemical synthesis;DNA/*chemical synthesis;Support, U.S. Gov't, P.H.S.;Templates, Genetic;*Cytarabine}, Number = {13}, Organization = {Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06510.}, Pages = {4698-705}, Pubmed = {2458756}, Title = {Functional consequences of the arabinosylcytosine structural lesion in DNA}, Uuid = {B9F64701-A6C7-4111-8B4E-D9447F819D36}, Volume = {27}, Year = {1988}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2458756}} @article{Milh:2006, Abstract = {Delta-brush is the dominant pattern of rapid oscillatory activity (8-25 Hz) in the human cortex during the third trimester of gestation. Here, we studied the relationship between delta-brushes in the somatosensory cortex and spontaneous movements of premature human neonates of 29-31 weeks postconceptional age using a combination of scalp electroencephalography and monitoring of motor activity. We found that sporadic hand and foot movements heralded the appearance of delta-brushes in the corresponding areas of the cortex (lateral and medial regions of the contralateral central cortex, respectively). Direct hand and foot stimulation also reliably evoked delta-brushes in the same areas. These results suggest that sensory feedback from spontaneous fetal movements triggers delta-brush oscillations in the central cortex in a somatotopic manner. We propose that in the human fetus in utero, before the brain starts to receive elaborated sensory input from the external world, spontaneous fetal movements provide sensory stimulation and drive delta-brush oscillations in the developing somatosensory cortex contributing to the formation of cortical body maps.}, Author = {Milh, and Kaminska, and Huon, and Lapillonne, and Ben-Ari, and Khazipov,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {9}, Nlm_Id = {9110718}, Organization = {INMED/INSERM U29, Universit{\'e} de la M{\'e}diterran{\'e}e, Marseille, France.}, Pii = {bhl069}, Pubmed = {16950867}, Title = {Rapid Cortical Oscillations and Early Motor Activity in Premature Human Neonate}, Uuid = {D1FD7FA7-A949-4067-BCCC-D34A521D9756}, Year = {2006}, url = {papers/Milh_CerebCortex2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhl069}} @article{Milh:2007, Abstract = {PURPOSE: To determine the electrophysiological pattern and propose a clinical relevance of a deficient glutamate transport in the developing brain. METHODS: (a) Surface EEG-video monitoring in freely moving pups; (b) intracortical multiple unit activity (MUA) and local field potential recordings in 5- to 7-day-old rats after pharmacological inhibition of the glutamate transporters by DL-TBOA. RESULTS: Glutamate transporters inhibition alters the background cortical electrical activity inducing a dominant and persistent pattern of bilateral recurrent paroxysmal bursts alternating with periods of hypoactivity and also partial seizures. Intracortical local field recordings show that paroxysmal bursts are associated with multiunits and gamma oscillations separated by periods of silence. This cortical activity involves the activation of ionotropic glutamate receptors and was not observed after kainate and pilocarpine administration. CONCLUSIONS: We show that a dysfunction of glutamate transporters in immature rats leads to a singular cortical activity that is reminiscent of a "suppression-burst" pattern. We propose that an early deficiency of glutamate transport may underlie some early onset epilepsies.}, Author = {Milh, Mathieu and Becq, H{\'e}l\`{e}ne and Villeneuve, Nathalie and Ben-Ari, Yehezkel and Aniksztejn, Laurent}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;Epilepsy;development;in vivo;rat;Neocortex;Seizures}, Month = {1}, Nlm_Id = {2983306R}, Number = {1}, Organization = {INMED/INSERM U29, Universit{\'e} de la Mediterran{\'e}e, Marseille, France.}, Pages = {169-74}, Pii = {EPI839}, Pubmed = {17241224}, Title = {Inhibition of glutamate transporters results in a "suppression-burst" pattern and partial seizures in the newborn rat}, Uuid = {F35DBACA-5FCC-4932-99E2-7E352A252B89}, Volume = {48}, Year = {2007}, url = {papers/Milh_Epilepsia2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1528-1167.2006.00839.x}} @article{Miller:1988, Abstract = {The use of an exogenously administered thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), for studies of the proliferation, migration and time of origin of cells in the cerebral cortex was investigated and compared with [3H]thymidine [( 3H]dT) autoradiography. Pregnant rats or mice were injected with BrdU and/or [3H]dT and processed by standard immunohistochemical techniques using a primary antibody directed against BrdU in single-stranded DNA, autoradiographic methods, or both. In animals that survived only 1 h after the injection, BrdU-positive cells were distributed in the proliferative zones throughout the central nervous system (CNS). In animals killed 1-3 days after the BrdU injection, intensely immunoreactive cells were in the superficial cortical plate and less intensely labeled cells were scattered throughout the deep cortical plate, the intermediate zone, and the germinal zones. In adult animals, 60 days or more after an injection of BrdU on GD 19, BrdU-positive cells were located in layer II/III of neocortex, the hippocampal pyramidal layer, and the granule layer of the dentate gyrus. In the double-labeling studies, the distribution of BrdU-immunoreactive cells was identical to that of autoradiographically labeled cells, and all autoradiographically labeled neurons were BrdU positive. Thus, BrdU immunohistochemistry is suitable for developmental studies of the CNS; moreover, it provides several advantages over [3H]dT autoradiography.}, Author = {Miller, M. W. and Nowakowski, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Pregnancy;Cell Differentiation;Animals;Rats;Comparative Study;Brain;Thymidine;Female;Cell Movement;23 Technique;Rats, Inbred Strains;Time Factors;01 Adult neurogenesis general;Research Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Immunohistochemistry;Autoradiography;Bromodeoxyuridine;Research Support, Non-U.S. Gov't}, Medline = {89002086}, Month = {8}, Nlm_Id = {0045503}, Number = {1}, Organization = {Department of Anatomy, School of Osteopathic Medicine, University of Medicine and Dentistry of New Jersey, Piscataway 08854.}, Pages = {44-52}, Pii = {0006-8993(88)90055-8}, Pubmed = {3167568}, Title = {Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system}, Uuid = {01DF6DA8-42A3-11DB-A5D2-000D9346EC2A}, Volume = {457}, Year = {1988}} @article{Miller:1981, Abstract = {Lesions were produced in the nasal-superior quadrant of rat retinas at 1 day postnatal. Both the optic fiber and ganglion cell layers were destroyed at the lesion site. Retrograde changes in the more peripherally located ganglion cell bodies, their optic fibers, and neuroglia were monitored by light and electron microscopy. No optic fibers remained in the region peripheral to the lesion site after 2 days postoperative (DPO). Neither regenerative sprouting nor axonal ingrowth from late-maturing ganglion cells in the retinal periphery was observed. Cell death of the large and the majority of medium ganglion cell bodies was very rapid as was clearing of the degeneration products. These processes peaked at 1 DPO and were complete by 2 DPO. Microglia and Mueller cell cytoplasm actively phagocytized degenerating ganglion cell bodies and their optic fibers. A stable population of cell bodies in the ganglion cell layer peripheral to the lesion remained intact from 2 DOP to 21 DPO. The surviving somata were consistently 65\%of the control ganglion cell population, and they remained after their axons had degenerated. The cell bodies measured 6-12.1 micron in diameter, a range which included the small cell population and a few of the medium cells. Dendritic patterning, used to designate ganglion cell types, corroborated their classification as small and medium ganglion cells. Morphological changes in these perikarya due to axotomy were limited to a mild chromatolytic response.}, Author = {Miller, N. M. and Oberdorfer, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Retina;Cell Differentiation;Nerve Degeneration;Animals;Phagocytosis;Rats;Cell Count;Optic Nerve;Rats, Inbred Strains;Axons;Not relevant;11 Glia;Dendrites;Nerve Regeneration;Neurons;Neuroglia;Support, U.S. Gov't, P.H.S.;Microscopy, Electron;Nerve Fibers}, Medline = {82053649}, Month = {11}, Nlm_Id = {0406041}, Number = {4}, Pages = {493-504}, Pubmed = {7298911}, Title = {Neuronal and neuroglial responses following retinal lesions in the neonatal rats}, Uuid = {3BA3171C-7A45-4FAF-9F20-492B9AC36D72}, Volume = {202}, Year = {1981}} @article{Miller:1993, Abstract = {Postmitotic neurons migrate from a zone(s) near the ventricles to the neocortex. During this migration, neurons associate with radial glia. After serving their role as guides for neuronal migration, the radial glia transform into astrocytes. Prenatal exposure to ethanol causes abnormal neuronal migration. We examined the effects of gestational exposure to ethanol on radial glia and astrocytes. Radial glia were stained immunohistochemically with the antibody RAT-401, and astrocytes were labeled with an antibody directed against glial fibrillary acidic protein (GFAP). The subjects were the offspring of rats fed an ethanol- containing liquid diet (Et), pair-fed a liquid control diet (Ct), or fed chow and water (Ch). During the first postnatal week, radial glial fibers (in Et-treated rats and controls) stretched from the ventricular surface through the developing cerebral wall to the pial surface. In the Et-treated rats, the radial processes were less dense and more poorly fasciculated than they were in the Ch- and Ct-treated rats. Moreover, by postnatal day (P) 5, there was a significant reduction in RAT-401 immunostaining in the Et-treated rats, particularly in the superficial cortex. A similar reduction in control rats did not begin until P10. In all three treatment groups, GFAP-immunoreactive astrocytes were in the cortex throughout the period from P1 to P45. In neonates, GFAP-positive cells were distributed in the marginal zone (layer I) and the intermediate zone (the white matter). The number of GFAP-positive cells in the cortical plate increased steadily with time so that, by P26, GFAP-immunoreactive astrocytes were distributed evenly through all cortical laminae. Interestingly, between P5 and P12, the number of astrocytes was significantly greater in Et-treated rats than in controls. Thus prenatal exposure to ethanol induces the premature loss of RAT-401-positive processes and the precocious increase in GFAP immunostaining. These ethanol-induced changes in glial development indicate that ethanol accelerates the transformation of radial glia into astrocytes. Moreover, the ethanol-induced premature degradation of the network of radial glial fibers may underlie the migration of late- generated neurons to ectopic sites.}, Author = {Miller, M. W. and Robertson, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Comp Neurol}, Keywords = {Rats, Sprague-Dawley;Prenatal Exposure Delayed Effects;Neuroglia/*drug effects;Female;Rats;Glial Fibrillary Acidic Protein/immunology/metabolism;Ethanol/*pharmacology;Astrocytes/*drug effects;11 Glia;Animal;Pregnancy;Support, U.S. Gov't, P.H.S.;G;Cerebral Cortex/*cytology/drug effects/*growth &development}, Number = {2}, Organization = {Research Service, Veterans Affairs Medical Center, Iowa City, Iowa 52246.}, Pages = {253-66.}, Title = {Prenatal exposure to ethanol alters the postnatal development and transformation of radial glia to astrocytes in the cortex}, Uuid = {40A39CF4-74CA-4B85-AD7D-1B7C379A735E}, Volume = {337}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8276999}} @article{Miller:2007, Abstract = {DNA methylation is a covalent chemical modification of DNA catalyzed by DNA methyltransferases (DNMTs). DNA methylation is associated with transcriptional silencing and has been studied extensively as a lifelong molecular information storage mechanism put in place during development. Here we report that DNMT gene expression is upregulated in the adult rat hippocampus following contextual fear conditioning and that DNMT inhibition blocks memory formation. In addition, fear conditioning is associated with rapid methylation and transcriptional silencing of the memory suppressor gene PP1 and demethylation and transcriptional activation of the synaptic plasticity gene reelin, indicating both methyltransferase and demethylase activity during consolidation. DNMT inhibition prevents the PP1 methylation increase, resulting in aberrant transcription of the gene during the memory-consolidation period. These results demonstrate that DNA methylation is dynamically regulated in the adult nervous system and that this cellular mechanism is a crucial step in memory formation.}, Author = {Miller, Courtney A. and Sweatt, J. David}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Phosphoprotein Phosphatase;Animals;Fear;Rats;Enzyme Inhibitors;Memory;DNA;Models, Biological;Rats, Sprague-Dawley;Hippocampus;Cell Adhesion Molecules, Neuronal;Azacitidine;research support, non-u.s. gov't;Behavior, Animal;Gene Expression Regulation, Enzymologic;Reverse Transcriptase Polymerase Chain Reaction;Male;Serine Endopeptidases;Extracellular Matrix Proteins;Conditioning, Classical;21 Neurophysiology;DNA (Cytosine-5-)-Methyltransferase;research support, n.i.h., extramural;24 Pubmed search results 2008;Nerve Tissue Proteins;DNA Methylation}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Neurobiology and the Evelyn F. McKnight Brain Institute,University of Alabama at Birmingham, Birmingham, AL 35294, USA.}, Pages = {857-69}, Pii = {S0896-6273(07)00142-0}, Pubmed = {17359920}, Title = {Covalent modification of DNA regulates memory formation}, Uuid = {B2347B89-1B63-4C82-9C78-3F0A365CF6B0}, Volume = {53}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.02.022}} @article{Miller:2007a, Abstract = {During development of the mammalian nervous system, neural stem cells generate neurons first and glia second, thereby allowing the initial establishment of neural circuitry, and subsequent matching of glial numbers and position to that circuitry. Here, we have reviewed work addressing the mechanisms underlying this timed cell genesis, with a particular focus on the developing cortex. These studies have defined an intriguing interplay between intrinsic epigenetic status, transcription factors, and environmental cues, all of which work together to establish this fascinating and complex biological timing mechanism.}, Author = {Miller, Freda D. and Gauthier, Andr{\'e}e S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Developmental & Stem Cell Biology, Hospital for Sick Children, Toronto M5G 1X8, Canada; Department of Molecular & Medical Genetics, University of Toronto, Toronto M5S 1A8, Canada; Department of Physiology, University of Toronto, Toronto M5S 1A8, Canada.}, Pages = {357-69}, Pii = {S0896-6273(07)00298-X}, Pubmed = {17481390}, Title = {Timing Is Everything: Making Neurons versus Glia in the Developing Cortex}, Uuid = {FE52E7C9-5829-4E58-BE62-118B159DF3E2}, Volume = {54}, Year = {2007}, url = {papers/Miller_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.04.019}} @article{Miller:2006, Author = {Miller, Greg}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Mice;Mutation;Neurons;Methyl-CpG-Binding Protein 2;Phosphorylation;24 Pubmed search results 2008;Female;Gene Silencing;Rett Syndrome;Brain-Derived Neurotrophic Factor;Mental Disorders;Animals;Brain;Corticotropin-Releasing Hormone;Humans;news}, Month = {12}, Nlm_Id = {0404511}, Number = {5805}, Pages = {1536-7}, Pii = {314/5805/1536}, Pubmed = {17158303}, Title = {Neuroscience. Getting a read on Rett syndrome}, Uuid = {94669E2F-9585-41E0-8FDC-4DA747AD87B8}, Volume = {314}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.314.5805.1536}} @article{Milligan:1991, Abstract = {Brain macrophages and microglia play important roles in central nervous system (CNS) development, especially during regressive events in which particular neuronal and glial constituents are eliminated. The purpose of this study is to provide a complete map of brain macrophage and microglia distribution in all regions of the neuraxis from birth to sexual maturity. We have utilized morphology and immunostaining with the specific antibodies OX-42 and ED1 to distinguish between brain macrophages and microglia. Brain macrophages are large, round cells, 10-15 microns in diameter, with few or no cytoplasmic processes; these cells are ED1- and OX-42-immunopositive. Microglia have small cell bodies with numerous, ramified cytoplasmic processes. These cells are OX-42-positive, and ED1-negative. We found a specific pattern of distribution of brain macrophages, targeting specific cortical and subcortical areas transiently, including developing fiber tracts. These cells disappeared completely by the third postnatal week. In contrast, OX-42-positive microglia exhibited a gradual increase in number and were distributed uniformly throughout gray matter and within white matter tracts. These cells remain in the adult CNS, constituting the resident microglia population. We suggest that these two distinct phagocytic cell populations perform unique functions in the developing brain, including remodeling of restricted CNS areas by brain macrophages that is part of a normal morphological process.}, Author = {Milligan, C. E. and Cunningham, T. J. and Levitt, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:36 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Neuroglia;Immunohistochemistry;Antibodies, Monoclonal;Rats;11 Glia;Animals, Newborn;Macrophages;Support, U.S. Gov't, P.H.S.;Animals;Brain}, Medline = {92184999}, Month = {12}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19129.}, Pages = {125-35}, Pubmed = {1797868}, Title = {Differential immunochemical markers reveal the normal distribution of brain macrophages and microglia in the developing rat brain}, Uuid = {34DBBCE6-B9F4-11DA-93EA-000D9346EC2A}, Volume = {314}, Year = {1991}} @article{Milne:2005, Abstract = {Ischaemia induces activation of resident microglia and infiltration of peripheral monocyte/macrophage cells into the central nervous system. The role of scavenger receptors, receptors critical to the recognition and clearance of cell debris, has not been investigated during cerebral ischaemia. MARCO is an inducible member of the scavenger receptor family unique to cells of monocytic lineage and is a cell surface marker that plays a critical role in the differentiation of monocytes to dendritic cells. To understand the role of MARCO in cerebral ischaemia, we investigated its expression in mice following middle cerebral artery (MCA) occlusion. No MARCO mRNA expression was observed in naive mouse brain. There was no significant increase in expression of MARCO mRNA following transient occlusion (60min) of the MCA at any time point up to 24 h. However, a significant, marked increase in MARCO mRNA expression was observed at 24 h in the cortex of mouse brains after a permanent occlusion of the MCA. The increased expression of MARCO mRNA at 24 h after prolonged ischaemia is consistent with its putative role in the clearance of debris and/or degenerating cells after severe ischaemia and supports previous publications showing the presence of dendritic cells around permanently occluded lesions.}, Author = {Milne, Stuart A. and McGregor, Ailsa L. and McCulloch, James and Sharkey, John}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {11 Glia}, Nlm_Id = {7600130}, Number = {1-2}, Organization = {Astellas CNS in Edinburgh, The University of Edinburgh, UK. stuart.miline\@ed.ac.uk}, Pages = {58-62}, Pii = {S0304-3940(05)00355-1}, Pubmed = {15936512}, Title = {Increased expression of macrophage receptor with collagenous structure (MARCO) in mouse cortex following middle cerebral artery occlusion}, Uuid = {8BD875D7-32DC-4BDC-A231-773F389979F6}, Volume = {383}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2005.03.065}} @article{Milward:2005, Abstract = {The phenomenon of colossal magnetoresistance in manganites is generally agreed to be a result of competition between crystal phases with different electronic, magnetic and structural order; a competition which can be strong enough to cause phase separation between metallic ferromagnetic and insulating charge-modulated states. Nevertheless, closer inspection of phase diagrams in many manganites reveals complex phases where the two order parameters of magnetism and charge modulation unexpectedly coexist. Here we show that such experiments can be naturally explained within a phenomenological Ginzburg-Landau theory. In contrast to models where phase separation originates from disorder or as a strain-induced kinetic phenomenon, we argue that magnetic and charge modulation coexist in new thermodynamic phases. This leads to a rich diagram of equilibrium phases, qualitatively similar to those seen experimentally. The success of this model argues for a fundamental reinterpretation of the nature of charge modulation in these materials, from a localized to a more extended 'charge-density wave' picture. The same symmetry considerations that favour textured coexistence of charge and magnetic order may apply to many electronic systems with competing phases. The resulting 'electronically soft' phases of matter with incommensurate, inhomogeneous and mixed order may be general phenomena in correlated systems.}, Author = {Milward, G. C. and Calder{\'o}n, M. J. and Littlewood, P. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0410462}, Number = {7026}, Organization = {Cavendish Laboratory, Cambridge University, Madingley Road, Cambridge CB3 0HE, UK. gcm24\@cam.ac.uk}, Pages = {607-10}, Pii = {nature03300}, Pubmed = {15703740}, Title = {Electronically soft phases in manganites}, Uuid = {B7949D53-7E27-4899-8396-5F3F818677C9}, Volume = {433}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03300}} @article{Minlebaev:2007, Abstract = {Early in development, cortical networks generate particular patterns of activity that participate in cortical development. The dominant pattern of electrical activity in the neonatal rat neocortex in vivo is a spatially confined spindle-burst. Here, we studied network mechanisms of generation of spindle-bursts in the barrel cortex of neonatal rats using a superfused cortex preparation in vivo. Both spontaneous and sensory-evoked spindle-bursts were present in the superfused barrel cortex. Pharmacological analysis revealed that spindle-bursts are driven by glutamatergic synapses with a major contribution of AMPA/kainate receptors, but slight participation of NMDA receptors and gap junctions. Although GABAergic synapses contributed minimally to the pacing the rhythm of spindle-burst oscillations, surround GABAergic inhibition appeared to be crucial for their compartmentalization. We propose that local spindle-burst oscillations, driven by glutamatergic synapses and spatially confined by GABAergic synapses, contribute to the development of barrel cortex during the critical period of developmental plasticity.}, Author = {Minlebaev, Marat and Ben-Ari, Yehezkel and Khazipov, Rustem}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Excitatory Amino Acid Antagonists;gamma-Aminobutyric Acid;Animals;Rats;Neuronal Plasticity;Afferent Pathways;Glutamic Acid;Synaptic Transmission;Female;Neurons, Afferent;Vibrissae;Receptors, AMPA;Biological Clocks;research support, non-u.s. gov't;Rats, Wistar;Male;Nerve Net;Animals, Newborn;Action Potentials;Receptors, GABA-A;21 Neurophysiology;Somatosensory Cortex;GABA Antagonists;Trigeminal Nerve;21 Cortical oscillations;Interneurons;24 Pubmed search results 2008;Neural Inhibition}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {The Mediterranean Institute of Neurobiology/INSERM U29, 163 Avenue de Luminy, B.P. 13, 13273 Marseille, France.}, Pages = {692-700}, Pii = {00759.2006}, Pubmed = {17093125}, Title = {Network mechanisms of spindle-burst oscillations in the neonatal rat barrel cortex in vivo}, Uuid = {777C09E1-9D7F-405E-96EB-D87D55C6EEF8}, Volume = {97}, Year = {2007}, url = {papers/Minlebaev_JNeurophysiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00759.2006}} @article{Miragall:1982, Abstract = {The time interval between the incorporation of [3H]thymidine and the appearance of olfactory marker protein (OMP) in autoradiographically labeled neurons which have differentiated from stem cells, has been determined by autoradiographic and immunohistochemical techniques. The first [3H]thymidine-labeled, OMP-containing elements have been observed 7 days after administration of the radioactive thymidine. This result allows some speculation on the potential function of the olfactory marker protein.}, Author = {Miragall, F. and Monti Graziadei, G. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Brain Res}, Keywords = {13 Olfactory bulb anatomy;I;Cell Differentiation;Neurons/*physiology;Tritium;Fluorescent Antibody Technique;Kinetics;Autoradiography;Animal;Support, U.S. Gov't, Non-P.H.S.;DNA Replication;Nerve Tissue Proteins/*analysis;Support, Non-U.S. Gov't;Male;Mice;Mice, Inbred Strains;Olfactory Bulb/*physiology}, Number = {1}, Pages = {245-50.}, Title = {Experimental studies on the olfactory marker protein. II. Appearance of the olfactory marker protein during differentiation of the olfactory sensory neurons of mouse: an immunohistochemical and autoradiographic study}, Uuid = {C409DE67-CB5A-4BDD-8AC2-C0979B305563}, Volume = {239}, Year = {1982}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7046875}} @article{Mirescu:2006, Abstract = {Prolonged sleep deprivation is stressful and has been associated with adverse consequences for health and cognitive performance. Here, we show that sleep deprivation inhibits adult neurogenesis at a time when circulating levels of corticosterone are elevated. Moreover, clamping levels of this hormone prevents the sleep deprivation-induced reduction of cell proliferation. The recovery of normal levels of adult neurogenesis after chronic sleep deprivation occurs over a 2-wk period and involves a temporary increase in new neuron formation. This compensatory increase is dissociated from glucocorticoid levels as well as from the restoration of normal sleep patterns. Collectively, these findings suggest that, although sleep deprivation inhibits adult neurogenesis by acting as a stressor, its compensatory aftereffects involve glucocorticoid-independent factors.}, Author = {Mirescu, Christian and Peters, Jennifer D. and Noiman, Liron and Gould, Elizabeth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {7505876}, Number = {50}, Organization = {Department of Psychology, Princeton University, Princeton, NJ 08544.}, Pages = {19170-5}, Pii = {0608644103}, Pubmed = {17135354}, Title = {Sleep deprivation inhibits adult neurogenesis in the hippocampus by elevating glucocorticoids}, Uuid = {A011A288-C511-4D32-8570-83CE33B10304}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0608644103}} @article{Mischel:1995, Author = {Mischel, P. S. and Nguyen, L. P. and Vinters, H. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {10 Development;Child, Preschool;Humans;review;Female;Epilepsy;Infant;Severity of Illness Index;21 Dysplasia-heterotopia;Child;Male;10 genetics malformation;21 Neurophysiology;research support, u.s. gov't, p.h.s.;Adult;Cerebral Cortex;Infant, Newborn;24 Pubmed search results 2008;Immunohistochemistry;Adolescent}, Month = {3}, Nlm_Id = {2985192R}, Number = {2}, Organization = {Department of Pathology and Laboratory Medicine, UCLA Medical Center 90024-1732.}, Pages = {137-53}, Pubmed = {7876884}, Title = {Cerebral cortical dysplasia associated with pediatric epilepsy. Review of neuropathologic features and proposal for a grading system}, Uuid = {D436FF9A-1D63-4DE0-813D-FFD84D47B092}, Volume = {54}, Year = {1995}} @article{Mishima:2007, Abstract = {Glial cells have traditionally been considered to play supportive roles in the central nervous system. As recent experimental evidence suggests glial cells' participation in neural information processing, there has been a need to monitor the physiology of glial cells in vivo in the matured brain. Concurrently, identification and classification of the recorded glial cells is essential as there are at least several different kinds of glial cells. Past studies have achieved in vivo intracellular electrophysiological recording of glial cells using sharp glass microelectrodes, however, morphological recovery and identification of the recorded cells have hardly been done, due to technical difficulties. We demonstrate that use of large fragment biotinylated dextran amine (BDA) is an effective way to label a single glial cell recorded with a sharp microelectrode in vivo. Furthermore, the tracer signal amplification was achieved by a combination of avidin biotinylated horseradish peroxidase macromolecular complex (ABC) and tyramide-based methods, making multiple immunohistochemistry feasible. Using the method described in this study, we have successfully recorded and labeled cortical glial cells including astrocytes, oligodendrocytes, and microglia.}, Author = {Mishima, Tsuneko and Sakatani, Seiichi and Hirase, Hajime}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008;23 Technique}, Month = {10}, Nlm_Id = {7905558}, Number = {1}, Organization = {Hirase Research Unit, Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.}, Pages = {32-40}, Pii = {S0165-0270(07)00306-8}, Pubmed = {17686526}, Title = {Intracellular labeling of single cortical astrocytes in vivo}, Uuid = {CDD2AE2A-3CDB-4782-B5AB-2045533EA757}, Volume = {166}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2007.06.021}} @article{Miskevich:2002, Abstract = {Recently, NMDA receptors (NMDARs) have been implicated in a cell contact-dependent suppression of sprouting in cultured Xenopus tectal neurons during an early period when neither AMPA/kainate (KA) receptors nor action potentials play a prominent role in cell-cell communication. We asked how the NMDA receptors function in the absence of the depolarizing effect of AMPA/KA receptor activity. We show that type II metabotropic glutamate receptors (mGluRs) can operate synergistically with NMDA receptors in the absence of AMPA/KA receptor function to suppress an early neurite sprouting response of the tectal neurons. Calcium imaging with fluo-3 AM and morphological analyses after exposure to glutamate receptor antagonists show that a combination of AMPA/KA receptor and type II mGluR blockers mimics the decrease in intracellular free calcium in response to glutamate and the structural effects produced by NMDA receptor antagonists in these cultures. Patch- clamp analyses confirmed a decrease in NMDA receptor-mediated currents with type II mGluR blockade, and 8-bromo cAMP application produced a decrease in NMDA receptor-mediated calcium influx. These data suggest that type II mGluRs potentiate NMDA receptor function by decreasing cAMP levels in tectal neurons. We also show that NMDARs exhibit low magnesium sensitivity in tectal neurons during the first few days in culture. Thus both metabotropic and ionotropic glutamate receptors can play a role in the contact-mediated suppression of ongoing sprouting at early neuron-neuron contacts before action potential activity.}, Author = {Miskevich, F. and Lu, W. and Lin, S. Y. and Constantine-Paton, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Calcium Signaling/drug effects/physiology;Receptors, Glutamate/*metabolism;13 Olfactory bulb anatomy;Synapses/drug effects/*metabolism/ultrastructure;I;In Vitro;Cells, Cultured;Excitatory Amino Acid Antagonists/pharmacology;Larva;Magnesium/pharmacology;Patch-Clamp Techniques;Animal;Receptors, N-Methyl-D-Aspartate/antagonists &inhibitors/metabolism;Corpora Quadrigemina;Calcium/metabolism;Time Factors;Cyclic AMP/metabolism;Xenopus laevis;Cell Surface Extensions/drug effects/*metabolism/ultrastructure;Receptors, Metabotropic Glutamate/antagonists &inhibitors/metabolism;Neurites/ultrastructure;Support, U.S. Gov't, P.H.S.;Neurons/drug effects/*metabolism/ultrastructure}, Number = {1}, Organization = {Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139-4307, USA.}, Pages = {226-38.}, Title = {Interaction between metabotropic and NMDA subtypes of glutamate receptors in sprout suppression at young synapses}, Uuid = {43AB19AB-C648-443E-95FD-19F6BD78CF0B}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11756506%20http://www.jneurosci.org/cgi/content/full/22/1/226%20http://www.jneurosci.org/cgi/content/abstract/22/1/226}} @article{Mission:1991, Abstract = {Three cell forms of astroglial lineage populate the prenatal and early postnatal murine cerebral wall. In the present review we consider the ontogeny of these cell forms with respect to histogenetic events of the perinatal period. Classic bipolar radial glial cells predominate prior to E17. The bipolar coexist with monopolar radial forms in the perinatal period. Both bipolar and monopolar radial forms coexist with multipolar astrocytes in the course of the first postnatal week and are ultimately succeeded by the multipolar cells. The shift from bipolar to monopolar radial forms is initially coincident with translocation of somata of bipolar cells from the ventricular zone to the upper intermediate zone and cortical strata. Arborization appears to occur both at the growing tips and along the shaft of the processes of both bipolar and monopolar radial cell types. As arborization continues, the processes of the monopolar radial cells come to resemble those of the multipolar astrocytes. Eventually the radial cells are fully transformed into the multipolar astrocytic forms. During this period of transition, radial processes in the cortex appear to be degenerating, suggesting that regressive processes contribute to the cytologic transformation. This sequence of transformations begins late in the period of neuronal migration and continues through the early stages of growth and differentiation in the murine cerebral cortex. The signals that induce these changes may arise from differentiating neurons within the cortex. These transformations occur at a time when radial glial fibers are no longer required as guides for neuronal migration, and the glial population assumes new roles related to the development and operation of cortical neuronal circuits. Using Smart Source Parsing}, Author = {Mission, J. P. and Takahashi, T. and Caviness, V. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Glia}, Keywords = {Staining and Labeling;Cell Differentiation;Cerebral Cortex/*cytology/embryology/growth &development;Antibodies, Monoclonal/diagnostic use;Astrocytes/chemistry/*cytology;Biological Markers;Animal;11 Glia;Fetal Development;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;G;Mice;Nerve Tissue Proteins/analysis;Glycogen/analysis}, Number = {2}, Organization = {Department of Neurology, Developmental Neurobiology, Massachusetts General Hospital, Harvard Medical School, Boston 02114.}, Pages = {138-48}, Title = {Ontogeny of radial and other astroglial cells in murine cerebral cortex}, Uuid = {A1E1E51E-94DC-4F2E-8011-B961E0894BCF}, Volume = {4}, Year = {1991}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1709615}} @article{Mitchell:2001, Abstract = {Layer I of the neocortex is a dense synaptic zone consisting of horizontal corticocortical and widespread layer VII projections, in addition to thalamic inputs. In order to determine the origin and extent of corticocortical and thalamocortical projections to layer I of the frontal/premotor area M2 of the rat neocortex, we have used fluorescent anatomical tracing methods to determine the precise sources of cortical and thalamic input to the rostral and caudal aspects of layer I of M2. Retrograde tracer diamidino yellow (DY), applied directly to the pial surface on rostral or caudal areas of rat M2 (RM2 and CM2, respectively) labeled cells ipsilaterally throughout layers II/III, V, and VII of the adjacent primary motor area and the parietal areas (SI and SII). In addition, retrograde transport labeled contralateral CM2 or RM2 in layers II/III and V at sites homotopic to either CM2 or RM2 application sites. Contralateral layer VII was retrogradely labeled by the application to layer I of CM2, but not by the RM2 application. Retrograde DY transport from layer I of RM2 or CM2 of was seen in the ventral medial (VM), ventral lateral (VL), and posterior (Po) thalamic nuclei. However layer I transport from CM2 additionally labeled the thalamic central medial (CM) nucleus, while the RM2 labeled the mediodorsal (MD) thalamic nucleus. Upon determination that thalamic nuclei VM and VL were of primary interest in this study, due to their dense retrograde labeling, injections of anterograde tracer rhodamine dextranamine (RDA) into VM or VL were performed in order to study the projection patterns of these nuclei to layer I of the frontal cortex. RDA injections into VM labeled fibers extending through layer I of both RM2 and CM2 and throughout the cingulate cortex. Injections of RDA into VL consistently labeled dense fibers in layer I of both CM2 and RM2, although labeling was sharply decreased anterior to CM2. This study adds to a growing body of evidence that projections to layer I from all sources of cortical input make a significant contribution to integration throughout the neocortex.}, Author = {Mitchell, B. D. and Cauller, L. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Rhodamines;Frontal Lobe;Rats, Sprague-Dawley;Ventral Thalamic Nuclei;Axonal Transport;Rats;Prefrontal Cortex;Dextrans;Neural Pathways;Fluorescent Dyes;Motor Cortex;Thalamus;Animals;24 Pubmed search results 2008;Neurons;Amidines}, Medline = {21577688}, Month = {12}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {University of Texas at Dallas, Neuroscience Program, Department of Human Development and Communication Sciences, GR41, 2601 N. Floyd Road, Richardson, TX 75083, USA. bartley.mitchell\@tch.harvard.edu}, Pages = {68-77}, Pii = {S0006899301030840}, Pubmed = {11720712}, Title = {Corticocortical and thalamocortical projections to layer I of the frontal neocortex in rats}, Uuid = {B5EBB038-9529-4D0B-97FD-2F570ACC3420}, Volume = {921}, Year = {2001}} @article{Mitchell:2001a, Abstract = {Flathead is a rat neurological mutant which is phenotypically characterized by a flattened cranium, resting tremor, ataxia, progressive paralysis of the hind limbs, and death at 3-4 weeks after birth. Previous studies showed that rats homozygous for the mutation have a dramatically reduced brain size caused by a burst of apoptosis that begins after embryonic day 16 (E16) and which peaks at about E18. Late-developing structures such as the dentate gyrus, internal granule layer of the cerebellum, and superficial layers of the neocortex are severely depleted of cells. In the present study we have found that neurons and glia are both affected by the mutation. Immunohistochemical analysis with TAG-1, a marker for migratory neurons, revealed reduced staining in Fh neocortex and cerebellum, indicating that the mutation affects neuronal migration or a developmental event prior to it. Analysis of acutely dissociated neocortical cultures showed an accumulation of nestin-positive progenitor cells. Moreover, a substantial proportion of these progenitor cells were multinucleated with the nuclei organized as rosettes. Such multinucleated cells were also found in intact sections of the neocortex and the cerebellum where their presence was restricted to proliferative zones. Within the neocortex, the abundance of multinucleated progenitors is highest at E18 and decreases thereafter, thus correlating with the profile of cell death. This, along with the dramatically higher frequency of apoptosis among multinucleated cells, suggests that the aberrant cell death in Fh is due to defective cytokinesis that occurs in progenitor cells during late stages of brain development. 21441449 0165-3806 Journal Article}, Author = {Mitchell, B. D. and Gibbons, B. and Allen, L. R. and Stella, J. and D'Mello, S. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Rats;Giant Cells/chemistry/cytology;Neocortex/*abnormalities/pathology;Stem Cells/chemistry/*cytology;Neurons/chemistry/*cytology;Animal;Membrane Glycoproteins/analysis;CK;DNA/biosynthesis;Cerebellum/*abnormalities/pathology;Cell Division/genetics;In Situ Nick-End Labeling;Support, Non-U.S. Gov't;Skull/abnormalities;Intermediate Filament Proteins/analysis;Apoptosis/*genetics;Neuroglia/cytology;Rats, Mutant Strains}, Number = {1}, Organization = {Department of Molecular and Cell Biology, University of Texas at Dallas, 2601 North Floyd Road, Richardson, TX 75083, USA.}, Pages = {53-63}, Title = {Aberrant apoptosis in the neurological mutant Flathead is associated with defective cytokinesis of neural progenitor cells}, Uuid = {8850E816-6D6B-11DA-A4FE-000D9346EC2A}, Volume = {130}, Year = {2001}, url = {papers/Mitchell_BrainResDevBrainRes2001}} @article{Mitchell:2004, Abstract = {Over most of the past century of modern neuroscience, it was thought that the adult brain was completely incapable of generating new neurons. During the past 3 decades, research exploring potential neuronal replacement therapies has focused on replacing lost neurons by transplanting cells or grafting tissue into diseased regions of the brain. However, in the last decade, the development of new techniques has resulted in an explosion of new research showing that neurogenesis, the birth of new neurons, normally occurs in two limited and specific regions of the adult mammalian brain and that there are significant numbers of multipotent neural precursors in many parts of the adult mammalian brain. Recent advances in our understanding of related events of neural development and plasticity, including the role of radial glia in developmental neurogenesis and the ability of endogenous precursors present in the adult brain to be induced to produce neurons and partially repopulate brain regions affected by neurodegenerative processes, have led to fundamental changes in the views about how the brain develops as well as to approaches by which endogenous precursors might be recruited to repair the adult brain. Recruitment of new neurons can be induced in a region-specific, layer-specific and neuronal-type-specific manner, and, in some cases, newly recruited neurons can form long-distance connections to appropriate targets. Elucidation of the relevant molecular controls may both allow control over transplanted precursor cells and potentially allow the development of neuronal replacement therapies for neurodegenerative disease and other CNS injuries that do not require transplantation of exogenous cells.}, Author = {Mitchell, Bartley D. and Emsley, Jason G. and Magavi, Sanjay S. P. and Arlotta, Paola and Macklis, Jeffrey D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Cell Lineage;01 Adult neurogenesis general;Stem Cell Transplantation;Cell Differentiation;Central Nervous System Diseases;Research Support, Non-U.S. Gov't;17 Transplant Regeneration;Mammals;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Animals;Brain;Humans;review;Neurons}, Nlm_Id = {7809375}, Number = {2-4}, Organization = {MGH-HMS Center for Nervous System Repair, Department of Neurosurgery, Harvard Medical School, Massachusetts General Hospital, Boston, MA 02114, USA.}, Pages = {101-17}, Pii = {DNE20040262_4101}, Pubmed = {15711054}, Title = {Constitutive and induced neurogenesis in the adult mammalian brain: manipulation of endogenous precursors toward CNS repair}, Uuid = {636C848A-659B-4E35-A7C4-10A34EAB5351}, Volume = {26}, Year = {2004}, url = {papers/Mitchell_DevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000082131}} @article{Mitchell:1999, Abstract = {OBJECTIVE: To examine the nature and frequency of anterior temporal lobe (AT) abnormalities that occur in intractable temporal lobe epilepsy (TLE). METHODS: We reviewed the MR scans and clinical histories of 50 consecutive patients with intractable TLE. Histopathology was available in 42 surgically treated cases. RESULTS: MRI demonstrated loss of the gray-white matter differentiation and decreased T1- and increased T2-weighted signal in the ipsilateral AT in 58\%of the 50 patients. This appearance was observed in 64\%of the 36 patients with hippocampal sclerosis (HS) but was also seen in patients without HS. These changes were associated with temporal lobe atrophy, a higher hippocampal T2 relaxation time, and a history of febrile convulsions. Pathologic examination showed that the MRI appearances were not caused by dysplasia, degenerative abnormalities, or inflammatory change. Histologic quantitation showed increased glial cell nuclei counts in the intractable TLE cases compared with controls. There was no difference in glial cell numbers between cases with AT abnormality and those without this appearance. Presence or absence of changes was not predictive of preoperative neuropsychology, postoperative change in neuropsychology, or seizure outcome after surgery. CONCLUSIONS: These frequently seen ipsilateral changes are not caused by gliosis and may reflect a nonspecific increase in water content in the temporal lobe. This may be due to myelin abnormalities or some other as yet unidentified pathologic factor.}, Author = {Mitchell, L. A. and Jackson, G. D. and Kalnins, R. M. and Saling, M. M. and Fitt, G. J. and Ashpole, R. D. and Berkovic, S. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {Neuropsychological Tests;Adolescent;Magnetic Resonance Imaging;Child, Preschool;Humans;Treatment Outcome;Middle Aged;Female;Child;Atrophy;clinical trial;Male;Analysis of Variance;controlled clinical trial;Epilepsy, Temporal Lobe;Adult;Temporal Lobe;Research Support, Non-U.S. Gov't}, Medline = {99129732}, Month = {1}, Nlm_Id = {0401060}, Number = {2}, Organization = {Brain Imaging Research Institute, Austin and Repatriation Medical Centre, Heidelberg, Victoria, Australia.}, Pages = {327-36}, Pubmed = {9932952}, Title = {Anterior temporal abnormality in temporal lobe epilepsy: a quantitative MRI and histopathologic study}, Uuid = {AD8B2A63-A3E5-11DA-AB00-000D9346EC2A}, Volume = {52}, Year = {1999}} @article{Mitrasinovic:2005, Abstract = {Microglia with increased expression of the macrophage colony-stimulating factor receptor (M-CSFR; c-fms) are found surrounding plaques in Alzheimer's disease (AD) and in mouse models for AD and after ischemic or traumatic brain injury. Increased expression of M-CSFR causes microglia to adopt an activated state that results in proliferation, release of cytokines, and enhanced phagocytosis. To determine whether M-CSFR-induced microglial activation affects neuronal survival, we assembled a coculture system consisting of BV-2 microglia transfected to overexpress the M-CSFR and hippocampal organotypic slices treated with NMDA. Twenty-four hours after assembly of the coculture, microglia overexpressing M-CSFR proliferated at a higher rate than nontransfected control cells and exhibited enhanced migration toward NMDA-injured hippocampal cultures. Surprisingly, coculture with c-fms-transfected microglia resulted in a dramatic reduction in NMDA-induced neurotoxicity. Similar results were observed when cocultures were treated with the teratogen cyclophosphamide. Biolistic overexpression of M-CSFR on microglia endogenous to the organotypic culture also rescued neurons from excitotoxicity. Furthermore, c-fms-transfected microglia increased neuronal expression of macrophage colony-stimulating factor (M-CSF), the M-CSFR, and neurotrophin receptors in the NMDA-treated slices, as determined with laser capture microdissection. In the coculture system, direct contact between the exogenous microglia and the slice was necessary for neuroprotection. Finally, blocking expression of the M-CSF ligand by exogenous c-fms-transfected microglia with a hammerhead ribozyme compromised their neuroprotective properties. These results demonstrate a protective role for microglia overexpressing M-CSFR in our coculture system and suggest under certain circumstances, activated microglia can help rather than harm neurons subjected to excitotoxic and teratogen-induced injury.}, Author = {Mitrasinovic, Olivera M. and Grattan, Alicia and Robinson, Christopher C. and Lapustea, Nicolae B. and Poon, Clara and Ryan, Heather and Phong, Connie and Murphy, Greer M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {17}, Organization = {Neuroscience Research Laboratories, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California 94305, USA.}, Pages = {4442-51}, Pii = {25/17/4442}, Pubmed = {15858070}, Title = {Microglia overexpressing the macrophage colony-stimulating factor receptor are neuroprotective in a microglial-hippocampal organotypic coculture system}, Uuid = {8050F9BD-2870-4960-9BD5-352AC3044BC2}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0514-05.2005}} @article{Mitrasinovic:2003, Abstract = {Macrophage colony stimulating factor (M-CSF) and its receptor are upregulated in the brain in Alzheimer's disease. M-CSF induces activation and proliferation of microglial cells and expression of proinflammatory cytokines. Amyloid beta (Abeta) immunization experiments suggest that microglia have the capacity to aggressively clear Abeta from the brain under certain circumstances. We examined the role of M-CSF in phagocytosis of fluorescent microspheres and Abeta by cultured microglia. M-CSF treatment increased microglial cell phagocytosis of both microspheres and of Abeta. Antibody neutralization of M-CSF inhibited Abeta uptake induced by overexpression of the M-CSF receptor on microglia. These results suggest that M-CSF could be important in promoting microglial clearance of abnormal protein aggregates such as Abeta.}, Author = {Mitrasinovic, Olivera M. and Vincent, Valerie A. M. and Simsek, Dilek and Murphy, Greer M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Amyloid beta-Protein;Flow Cytometry;Peptide Fragments;Research Support, Non-U.S. Gov't;Macrophage Colony-Stimulating Factor;Cell Line;Research Support, U.S. Gov't, P.H.S.;Fluorescent Dyes;11 Glia;Microglia;Microspheres;Animals;Mice;Phagocytosis}, Medline = {22697620}, Month = {7}, Nlm_Id = {7600130}, Number = {3}, Organization = {Neuroscience Research Laboratories, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5485, USA.}, Pages = {185-8}, Pii = {S0304394003004749}, Pubmed = {12812836}, Title = {Macrophage colony stimulating factor promotes phagocytosis by murine microglia}, Uuid = {F92DE338-4087-4D1D-AA79-394774E93B0C}, Volume = {344}, Year = {2003}, url = {papers/Mitrasinovic_NeurosciLett2003.pdf}} @article{Miyakoshi:2001, Abstract = {Neurons from the anterior subventricular zone (SVZ) of the cerebral cortex migrate tangentially to become interneurons in the olfactory bulb during development and in adult rodents. This migration was defined as neuronophilic, independent of a radial glial substrate. The cortical SVZ and the rostral migratory stream to the olfactory bulb were shown to be rich in 9-O-acetyl GD3 gangliosides (9-O-acGD3), which have been previously shown to be implicated in gliophilic migration in the rodent cerebral cortex and cerebellum. In the present study, we performed SVZ explant cultures using rats during their first postnatal week to analyze the expression of these gangliosides in chain migration of neuronal precursors. We characterized migrating chains of these neuroblasts through morphological analysis and immunocytochemistry for the neural cell adhesion molecule. By using the Jones monoclonal antibody which binds specifically to 9-O-acGD3 we showed that migrating chains from the SVZ explants express 9-O-acGD3 which is distributed in a punctate manner in individual cells. 9-O-acGD3 is also present in migrating chains that form in the absence of radial glia, typical of the neuronophilic chain migration of the SVZ. Our data indicate that 9- O-acetylated gangliosides may participate in neuronophilic as well as gliophilic migration.}, Author = {Miyakoshi, L. M. and Mendez-Otero, R. and Hedin-Pereira, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {Braz J Med Biol Res}, Keywords = {Neurons/*metabolism/ultrastructure;Cerebral Ventricles/cytology;Rats;Olfactory Bulb/*metabolism;C pdf;Animal;Gangliosides/analysis/*metabolism;Neuroglia/cytology;Cell Movement/*physiology;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Cerebral Cortex/cytology/*metabolism}, Number = {5}, Organization = {Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brasil.}, Pages = {669-73.}, Title = {The 9-O-acetyl GD3 gangliosides are expressed by migrating chains of subventricular zone neurons in vitro}, Uuid = {89D39105-291F-4F77-8FAE-1A882D2D66FD}, Volume = {34}, Year = {2001}, url = {papers/Miyakoshi_BrazJMedBiolRes2001}} @article{Miyata:2004, Abstract = {Mature neocortical layers all derive from the cortical plate (CP), a transient zone in the dorsal telencephalon into which young neurons are continuously delivered. To understand cytogenetic and histogenetic events that trigger the emergence of the CP, we have used a slice culture technique. Most divisions at the ventricular surface generated paired cycling daughters (P/P divisions) and the majority of the P/P divisions were asymmetric in daughter cell behavior; they frequently sent one daughter cell to a non-surface (NS) position, the subventricular zone (SVZ), within a single cell-cycle length while keeping the other mitotic daughter for division at the surface. The NS-dividing cells were mostly Hu+ and their daughters were also Hu+, suggesting their commitment to the neuronal lineage and supply of early neurons at a position much closer to their destiny than from the ventricular surface. The release of a cycling daughter cell to SVZ was achieved by collapse of the ventricular process of the cell, followed by its NS division. Neurogenin2 (Ngn2) was immunohistochemically detected in a certain cycling population during G1 phase and was further restricted during G2-M phases to the SVZ-directed population. Its retroviral introduction converted surface divisions to NS divisions. The asymmetric P/P division may therefore contribute to efficient neuron/progenitor segregation required for CP initiation through cell cycle-dependent and lineage-restricted expression of Ngn2.}, Author = {Miyata, Takaki and Kawaguchi, Ayano and Saito, Kanako and Kawano, Masako and Muto, Tetsuji and Ogawa, Masaharu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {10 Development;Transcription Factors;Animals;Gene Expression Regulation, Developmental;Epithelial Cells;Cell Cycle;Mitosis;Ki-67 Antigen;Models, Biological;Brain;Telencephalon;Cell Movement;Retroviridae;G2 Phase;Time Factors;Green Fluorescent Proteins;Cell Lineage;Cerebral Cortex;Neurons;Mice;Cell Division;G1 Phase;Immunohistochemistry;Collagen;Nerve Tissue Proteins;Stem Cells;Luminescent Proteins}, Month = {7}, Nlm_Id = {8701744}, Number = {13}, Organization = {Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, Saitama 351-0198, Japan. tmiyata\@med.nagoya-u.ac.jp}, Pages = {3133-45}, Pii = {dev.01173}, Pubmed = {15175243}, Title = {Asymmetric production of surface-dividing and non-surface-dividing cortical progenitor cells}, Uuid = {AB69CE3F-EB35-4EE7-B7D3-43D587AAAB71}, Volume = {131}, Year = {2004}, url = {papers/Miyata_Development2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.01173}} @article{Miyata:1999, Abstract = {NeuroD, a bHLH transcription factor, is implicated in differentiation of neurons and pancreatic beta cells. NeuroD-null mice die shortly after birth due to severe neonatal diabetes. To examine if there is postnatal neuronal phenotype in these mice, we rescued them from neonatal lethality by introducing a transgene encoding the mouse neuroD gene under the insulin promoter. These mice survive to adulthood but display severe neurological phenotype due to neuronal deficit in the granule layers of the cerebellum and hippocampus. We show here that NeuroD is required for these postnatally generated microneurons to undergo proper differentiation, the absence of which results in cell death.}, Author = {Miyata, T. and Maeda, T. and Lee, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0890-9369}, Journal = {Genes Dev}, Keywords = {Research Support, Non-U.S. Gov't;10 Development;Cell Differentiation;Animals;10 Hippocampus;Phenotype;Apoptosis;Cell Count;Mice, Transgenic;Hippocampus;Recombinant Fusion Proteins;Mice, Neurologic Mutants;Research Support, U.S. Gov't, P.H.S.;Gene Therapy;Mice, Knockout;Neurons;In Situ Nick-End Labeling;Insulin;Cerebellum;Mice;Promoter Regions (Genetics);Nerve Tissue Proteins;Transgenes}, Medline = {99328891}, Month = {7}, Nlm_Id = {8711660}, Number = {13}, Organization = {Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Boulder, Colorado 80309-0347, USA.}, Pages = {1647-52}, Pubmed = {10398678}, Title = {NeuroD is required for differentiation of the granule cells in the cerebellum and hippocampus}, Uuid = {33538635-E001-4773-86E0-B13136723BFD}, Volume = {13}, Year = {1999}, url = {papers/Miyata_GenesDev1999.pdf}} @article{Miyata:2001, Abstract = {Recent studies demonstrated the neuronogenic role of radial glial cells (RGCs) in the rodent. To reveal the fate of radial glial processes, we intensively monitored divisions of RGCs in DiI-labeled slices from the embryonic day 14 mouse cortex. During RGC division, each pia-connected fiber becomes thin but is neither lost nor divided; it is inherited asymmetrically by one daughter cell. In divisions that produce a neuron and a progenitor, the neuron inherits the pial fiber, also grows a thick ventricular process for several hours, and is therefore indistinguishable from the progenitor RGC. The ventricular process in the radial glial-like neuron ("radial neuron") then collapses, leading to ascent of the neuron by using the "recycled"radial fiber. 21453756 0896-6273 Journal Article}, Author = {Miyata, T. and Kawaguchi, A. and Okano, H. and Ogawa, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Neuron}, Keywords = {Fetus;10 Development;Neurons/*cytology/metabolism;Cerebral Cortex/cytology/*embryology/metabolism;Cell Movement/*physiology;Stem Cells/*cytology/metabolism;Aging/physiology;Animal;Cell Size/physiology;Cell Compartmentation/physiology;Cell Differentiation/*physiology;Mice, Inbred ICR;Support, Non-U.S. Gov't;Cell Division/*physiology;Body Patterning/physiology;Neuroglia/*cytology/metabolism;Nerve Tissue Proteins/metabolism;Cell Lineage/physiology;Mice;Immunohistochemistry;Neurites/metabolism/ultrastructure;Organ Culture;F}, Number = {5}, Organization = {Laboratory for Cell Culture Development, Brain Science Institute, RIKEN, 351-0198, Saitama, Japan. tmiyata\@brain.riken.go.jp}, Pages = {727-41}, Pubmed = {11567613}, Title = {Asymmetric inheritance of radial glial fibers by cortical neurons}, Uuid = {7CC4274D-7D83-421E-BEED-90D39FD09A02}, Volume = {31}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11567613}} @article{Mizrahi:2004, Abstract = {Structural changes in hippocampal dendrites and dendritic spines are thought to be a consequence of a wide range of experience- and activity-dependent manipulations. We explored the dynamics of hippocampal dendritic spines in vivo by developing a surgical preparation of the adult mouse brain that enabled two-photon imaging of fluorescently labeled CA1 pyramidal neurons. Dendritic trees and spines were repeatedly visualized over many hours in exquisite detail. We tested spine stability under both control conditions and during prolonged epileptic seizures. Remarkably, spines remained structurally stable after 30 min of experimental induction of epileptic seizures. Spines began to disappear only several hours after induction of epileptic activity. We thus demonstrate that this technique provides a methodology for direct in vivo optical studies of the intact mammalian hippocampus.}, Author = {Mizrahi, Adi and Crowley, Justin C. and Shtoyerman, Eran and Katz, Lawrence C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Pilocarpine;Animals;Microscopy, Confocal;Sensitivity and Specificity;Epilepsy;Mice, Transgenic;Hippocampus;Pyramidal Cells;23 Technique;Time Factors;Bicuculline;Dendrites;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;GABA Antagonists;Mice;18 Classic Neuroanatomy Physiology;Reproducibility of Results;Luminescent Proteins;Electroencephalography}, Month = {3}, Nlm_Id = {8102140}, Number = {13}, Organization = {Howard Hughes Medical Institute and Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. mizrahi\@neuro.duke.edu}, Pages = {3147-51}, Pii = {24/13/3147}, Pubmed = {15056694}, Title = {High-resolution in vivo imaging of hippocampal dendrites and spines}, Uuid = {8CC128E5-DC58-4DBF-A500-105F70EB3093}, Volume = {24}, Year = {2004}, url = {papers/Mizrahi_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5218-03.2004}} @article{Mizrahi:2003, Abstract = {In many regions of the adult mammalian brain, pronounced changes in synaptic input caused by lesions or severe sensory deprivation induce marked sprouting or retraction of neuronal dendrites. In the adult olfactory bulb, adult neurogenesis produces less pronounced, but continuously ongoing synapse turnover. To test the structural stability of adult dendrites in this context, we used two-photon microscopy to image dendrites of mitral and tufted (M/T) cells over prolonged periods in adult mice. Although pharmacologically increased activity could elicit morphological changes, under natural conditions such as ongoing neurogenesis, an odor-enriched environment or olfactory-based learning, M/T cell dendrites remained highly stable. Thus, in a context of ongoing adult synaptogenesis, dendritic stability could serve as a structural scaffold to maintain the organization of local circuits. 1097-6256 Journal Article}, Author = {Mizrahi, A. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Nat Neurosci}, Keywords = {Probability;Microscopy, Confocal/methods;Synapses/*physiology;Acetophenones/pharmacology;I pdf;Olfactory Bulb/*cytology/drug effects/physiology;Imaging, Three-Dimensional/instrumentation/methods;Animals;Electrophysiology;Aldehydes/pharmacology;Bacterial Proteins/genetics;Conditioning, Classical;Transfection/veterinary;Behavior, Animal;Dendrites/*physiology;Photons;Odors;Support, U.S. Gov't, P.H.S.;Luminescent Proteins/genetics;Comparative Study;13 Olfactory bulb anatomy;Nerve Net/*physiology;Action Potentials/drug effects;Time Factors;Neurons, Afferent/physiology/virology;Bicuculline/pharmacology;Dose-Response Relationship, Drug;Stimulation, Chemical;Discrimination Learning/physiology;Mice;Support, Non-U.S. Gov't;GABA Antagonists/pharmacology;Mice, Transgenic;Neuronal Plasticity/*physiology}, Number = {11}, Organization = {Howard Hughes Medical Institute and the Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. mizrahi\@neuro.duke.edu}, Pages = {1201-7}, Pubmed = {14528309}, Title = {Dendritic stability in the adult olfactory bulb}, Uuid = {7C6D760F-1DF7-4224-9388-3C6697F79983}, Volume = {6}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14528309}} @article{Mizrahi:2006, Abstract = {As a consequence of adult neurogenesis, the olfactory bulb (OB) receives a continuous influx of newborn neurons well into adulthood. However, their rates of generation and turnover, the factors controlling their survival, and how newborn neurons intercalate into adult circuits are largely unknown. To visualize the dynamics of adult neurogenesis, we produced a line of transgenic mice expressing GFP in approximately 70\%of juxtaglomerular neurons (JGNs), a population that undergoes adult neurogenesis. Using in vivo two-photon microscopy, time-lapse analysis of identified JGN cell bodies revealed a neuronal turnover rate of approximately 3\%of this population per month. Although new neurons appeared and older ones disappeared, the overall number of JGNs remained constant. This approach provides a dynamic view of the actual appearance and disappearance of newborn neurons in the vertebrate central nervous system, and provides an experimental substrate for functional analysis of adult neurogenesis.}, Author = {Mizrahi, Adi and Lu, Jing and Irving, Ryan and Feng, Guoping and Katz, Lawrence C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;02 Adult neurogenesis migration;13 Olfactory bulb anatomy}, Month = {2}, Nlm_Id = {7505876}, Number = {6}, Organization = {*Howard Hughes Medical Institute and Department of Neurobiology, Duke University Medical Center, Durham, NC 27710.}, Pages = {1912-7}, Pii = {0506297103}, Pubmed = {16446451}, Title = {In vivo imaging of juxtaglomerular neuron turnover in the mouse olfactory bulb}, Uuid = {C171D912-302A-4B1F-A80A-7B660E3BA20E}, Volume = {103}, Year = {2006}, url = {papers/Mizrahi_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0506297103}} @article{Mizumoto:2003, Abstract = {Neural progenitor cells isolated from the brains of neonatal GFP transgenic mice were grafted to the retina of RCS rats and rds and B6 mice. Expression of GFP and differentiation markers was evaluated at 1-4 weeks post-transplantation. Grafted cells maintained transgene expression throughout the 4-week period. At 1 week there was widespread migration of GFP+cells within the host retina and at 2 weeks evidence of neuronal differentiation (as shown by both marker expression and cell morphology), although integration at 4 weeks was limited to syngeneic recipients. Because brain-derived neural progenitor cells exhibit both neuronal and astrocytic differentiation in diseased and normal host retina, these cells provide a useful tool for studies of retinal regeneration.}, Author = {Mizumoto, Hiroyuki and Mizumoto, Keiko and Shatos, Marie A. and Klassen, Henry and Young, Michael J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0042-6989}, Journal = {Vision Res}, Keywords = {Retina;Mice, Inbred BALB C;Cell Differentiation;Animals;Stem Cell Transplantation;Rats;Transplantation, Heterologous;Brain;Indicators and Reagents;11 Glia;Green Fluorescent Proteins;Cell Line;Research Support, U.S. Gov't, P.H.S.;Mice;Luminescent Proteins;Stem Cells;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {22704539}, Month = {7}, Nlm_Id = {0417402}, Number = {16}, Organization = {The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.}, Pages = {1699-708}, Pii = {S0042698903002359}, Pubmed = {12818339}, Title = {Retinal transplantation of neural progenitor cells derived from the brain of GFP transgenic mice}, Uuid = {5DB7385D-9645-4E6C-9FD9-14645F907A31}, Volume = {43}, Year = {2003}} @article{Mizuno:1999, Abstract = {Telencephalin (TLCN) is a neuronal surface glycoprotein whose expression is restricted to the telencephalon, the most rostral segment of the brain. TLCN binds to lymphocyte function-associated antigen-1 (LFA-1) integrin. In the central nervous system, LFA-1 is selectively and constitutively expressed by microglia, suggesting that TLCN/LFA-1 binding may mediate cell-cell interactions between telencephalic neurons and microglia. In the present study, we investigated the effects of recombinant TLCN protein on the morphology of microglia. TLCN induced an intensive spreading of lamellipodia, causing a rapid change in microglial morphology. In contrast, TLCN induced no significant change in morphology of neuroblastoma and fibroblasts. Furthermore, the TLCN-induced spreading of microglia was accompanied by a clustering of LFA-1 on cell surface membrane. These results provide evidence that TLCN binding to the surface of microglia transduces signals into microglia that mediate or accelerate cell spreading and LFA-1 redistribution, implying that neuronal TLCN may control the state and/or function of microglia in both physiological and pathological conditions.}, Author = {Mizuno, T. and Yoshihara, Y. and Kagamiyama, H. and Ohsawa, K. and Imai, Y. and Kohsaka, S. and Mori, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Neuroblastoma;Animals;Cells, Cultured;Diencephalon;Recombinant Proteins;Microglia;L Cells (Cell Line);Tumor Suppressor Protein p53;Telencephalon;Genes, p53;Cell Movement;Animals, Newborn;Mice, Inbred Strains;Membrane Glycoproteins;Mice, Knockout;Tumor Cells, Cultured;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Lymphocyte Function-Associated Antigen-1;Neural Cell Adhesion Molecules}, Medline = {20074697}, Month = {12}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Wako, Japan.}, Pages = {58-66}, Pii = {S0006-8993(99)01984-8}, Pubmed = {10592287}, Title = {Neuronal adhesion molecule telencephalin induces rapid cell spreading of microglia}, Uuid = {628A3CB3-16B7-4C52-A72A-0D5D480936F6}, Volume = {849}, Year = {1999}} @article{Mizutani:2007, Abstract = {During brain development, neurons and glia are generated from a germinal zone containing both neural stem cells (NSCs) and more limited intermediate neural progenitors (INPs). The signalling events that distinguish between these two proliferative neural cell types remain poorly understood. The Notch signalling pathway is known to maintain NSC character and to inhibit neurogenesis, although little is known about the role of Notch signalling in INPs. Here we show that both NSCs and INPs respond to Notch receptor activation, but that NSCs signal through the canonical Notch effector C-promoter binding factor 1 (CBF1), whereas INPs have attenuated CBF1 signalling. Furthermore, whereas knockdown of CBF1 promotes the conversion of NSCs to INPs, activation of CBF1 is insufficient to convert INPs back to NSCs. Using both transgenic and transient in vivo reporter assays we show that NSCs and INPs coexist in the telencephalic ventricular zone and that they can be prospectively separated on the basis of CBF1 activity. Furthermore, using in vivo transplantation we show that whereas NSCs generate neurons, astrocytes and oligodendrocytes at similar frequencies, INPs are predominantly neurogenic. Together with previous work on haematopoietic stem cells, this study suggests that the use or blockade of the CBF1 cascade downstream of Notch is a general feature distinguishing stem cells from more limited progenitors in a variety of tissues.}, Author = {Mizutani, Ken-ichi and Yoon, Keejung and Dang, Louis and Tokunaga, Akinori and Gaiano, Nicholas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {24 Pubmed search results 2008;research support, non-u.s. gov't;Telencephalon;Basic Helix-Loop-Helix Leucine Zipper Transcription Factors;Signal Transduction;Stem Cells;research support, n.i.h., extramural;Green Fluorescent Proteins;Animals;Cells, Cultured;Mice;Neurons;Receptors, Notch}, Month = {9}, Nlm_Id = {0410462}, Number = {7160}, Organization = {Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, Pages = {351-5}, Pii = {nature06090}, Pubmed = {17721509}, Title = {Differential Notch signalling distinguishes neural stem cells from intermediate progenitors}, Uuid = {AB97042F-AD1E-4F32-875F-BB008B72DBA1}, Volume = {449}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06090}} @article{Mochida:2004, Abstract = {Widespread use of noninvasive brain imaging techniques, in particular magnetic resonance imaging, has led to increased recognition of genetic disorders of cortical development in recent years. The causative genes for many of these disorders have been identified through a combination of detailed clinical and radiological analyses and molecular genetic approaches. These disease genes have been found to affect different steps of cortical development, including proliferation of neuronal progenitor cells, neuronal migration, and maintaining integrity of the pial surface. In many cases, syndromes with similar clinical phenotypes are caused by genes with related biochemical functions. In this article, we review the recent advances in molecular genetic studies of the disorders of cortical development. The identification and functional studies of the genes associated with these developmental disorders will likely lead to improvement in diagnosis and facilitate our understanding of the mechanisms of cortical development.}, Author = {Mochida, Ganeshwaran H. and Walsh, Christopher A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0003-9942}, Journal = {Arch Neurol}, Keywords = {10 Development;Human;Animals;Humans;review, tutorial;review;21 Dysplasia-heterotopia;research support, non-u.s. gov't;Pia Mater;Molecular Biology;Support, Non-U.S. Gov't;Nervous System Malformations;Cerebral Cortex;Neurons;21 Neurophysiology;10 genetics malformation;Support, U.S. Gov't, P.H.S.;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0372436}, Number = {5}, Organization = {Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Boston, Mass, USA.}, Pages = {637-40}, Pii = {61/5/637}, Pubmed = {15148137}, Title = {Genetic basis of developmental malformations of the cerebral cortex}, Uuid = {8D537858-0125-11DB-9E68-000D9346EC2A}, Volume = {61}, Year = {2004}, url = {papers/Mochida_ArchNeurol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1001/archneur.61.5.637}} @article{Mody:1987, Abstract = {The effect of low extracellular Mg2+ concentration ([Mg2+]o) on neuronal activity was studied in rat hippocampal slices. After 20-40 min of perfusion with Mg2+-free medium, when [Mg2+]o declined to approximately 0.1-0.4 mM, spontaneous field potentials developed in the CA1 and CA3 regions, but not in the dentate gyrus. In the CA3 pyramidal cell layer, these potentials consisted of repetitive (0.3-0.5 Hz), 40- to 120-ms-long positive deflections (2-5 mV) with superimposed population spikes. In the stratum (str.) pyramidale of the CA1 region, positive-negative deflections (less than 3 mV) lasting for 30-80 ms were observed, which occurred with a frequency of 0.3-0.5 Hz. In some cases, longer lasting and rapidly recurring events were also observed. In CA3 pyramidal cells, the intracellular correlates of the field potential transients were 20- to 30-mV paroxysmal depolarization shifts (PDS) with superimposed bursts of action potentials, followed by large (greater than 10 mV), 500- to 1,200-ms-long afterhyperpolarizations (AHP). In contrast, pyramidal neurons of the CA1 area did not show PDSs; instead, sequences of excitatory postsynaptic potentials (EPSPs)/inhibitory postsynaptic potentials (IPSPs) accompanied the transient field potential changes. Occasionally, spontaneous EPSPs/IPSPs, occurring with high frequencies, could also be observed in CA1 without any field potential transients. In both hippocampal regions, the epileptiform activity evolved without significant alterations in the resting membrane potential (RMP) and input resistance (RN) of the neurons, although a 2- to 5-mV reduction in action potential threshold was noted. The spontaneous activity in Mg2+-free medium was readily suppressed by raising the extracellular Ca2+ concentration ([Ca2+]o) from 1.6 to 3.6 mM. The perfusion of 10-30 microns DL-2-amino-5-phosphonovaleric acid (2-APV), an antagonist for the glutamate receptors of the N-methyl-D-aspartate (NMDA) type, also attenuated or reversibly blocked the spontaneous activity. Surgical isolation of area CA1 from CA3 ceased the occurrence of the transients in CA1 but not in CA3. The synaptic input/output curves were shifted to the left in the absence of [Mg2+]o. Threshold intensity for eliciting population spikes was 50-75\%of that in normal medium. Paired-pulse facilitation was still present near threshold, but was reduced at higher stimulus intensities. Decreases in [Ca2+]o, produced by repetitive stimulation (20-Hz/5-10 s) of the Schaffer collateral/commissural pathway and monitored with ion-selective microelectrodes in the CA1 region, were enhanced in Mg2+-free medium.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Mody, I. and Lambert, J. D. and Heinemann, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {10 Development;Electrophysiology;Animals;Synapses;Rats;Synaptic Transmission;21 Epilepsy;Epilepsy;Hippocampus;Rats, Inbred Strains;research support, non-u.s. gov't;Male;Magnesium Deficiency;10 genetics malformation;21 Neurophysiology;Membrane Potentials;Spreading Cortical Depression;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {0375404}, Number = {3}, Pages = {869-88}, Pubmed = {3031235}, Title = {Low extracellular magnesium induces epileptiform activity and spreading depression in rat hippocampal slices}, Uuid = {A40B03B5-A04A-428A-8A09-7A10B3808D42}, Volume = {57}, Year = {1987}} @article{Moffett:1997, Abstract = {Experimental tumors of the central nervous system were investigated with antibodies to quinolinate to assess the cellular distribution of this endogenous neurotoxin. In advanced F98 and RG-2 glioblastomas and E367 neuroblastomas in the striatum of rats, variable numbers of quinolinate immunoreactive cells were observed in and around the tumors, with the majority being present within tumors, rather than brain parenchyma. The stained cells were morphologically variable, including round, complex, rod-shaped, and sparsely dendritic cells. Neuroblastoma and glioma cells were unstained, as were neurons, astrocytes, oligodendrocytes, ependymal cells, endothelial cells, and cells of the choroid plexus and leptomeninges. Glial fibrillary acidic protein immunoreactivity was strongly elevated in astrocytes surrounding the tumors. Dual labeling immunohistochemistry with antibodies to quinolinate and glial fibrillary acidic protein demonstrated that astrocytes and the cells containing quinolinate immunoreactivity were morphologically disparate and preferentially distributed external and internal to the tumors, respectively, and no dual labeled cells were observed. Lectin histochemistry with Griffonia simplicifolia B4 isolectin and Lycopersicon esculentum lectin demonstrated numerous phagocytic macrophages and reactive microglia in and around the tumors whose distribution was similar to that of quinolinate immunoreactive cells, albeit much more numerous. Dual labeling studies with antibodies to quinolinate and the lectins demonstrated partial codistribution of these markers, with most double-labeled cells having the morphology of phagocytes. The present findings suggest the possibility that quinolinate may serve a functional role in a select population of inflammatory cell infiltrates during the immune response to brain neoplasms.}, Author = {Moffett, J. R. and Els, T. and Espey, M. G. and Walter, S. A. and Streit, W. J. and Namboodiri, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Lectins;Neuroblastoma;Plant Lectins;Astrocytes;Corpus Striatum;Macrophages;Rats;Animals;Neoplasm Transplantation;Microglia;Female;Rats, Wistar;11 Glia;Not relevant;Brain Neoplasms;Tumor Stem Cells;Male;Glioblastoma;Rats, Inbred F344;Antibody Specificity;Quinolinic Acid;Organ Specificity;Support, U.S. Gov't, P.H.S.;Biological Markers;Inflammation;Nerve Tissue Proteins;Tryptophan Oxygenase;Glial Fibrillary Acidic Protein}, Medline = {97312389}, Month = {4}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Biology, Georgetown University, Washington, DC 20057-1229, USA.}, Pages = {287-301}, Pii = {S0014488696963657}, Pubmed = {9168830}, Title = {Quinolinate immunoreactivity in experimental rat brain tumors is present in macrophages but not in astrocytes}, Uuid = {F40CE37D-6170-4736-A653-0F901FF77EAF}, Volume = {144}, Year = {1997}, url = {papers/Moffett_ExpNeurol1997.pdf}} @article{Moga:2005, Abstract = {Annexin 7 (ANX7), also termed synexin, is a member of the annexin family of calcium-binding proteins. In the present study, we examined the distribution and cellular localization of ANX7-immunoreactivity in the rat hippocampus and its response to adrenalectomy (ADX). ANX7 was co-localized with OX42 in microglia distributed throughout the hippocampus of both control and ADX animals. ANX7-immunoreactivity was not detected in GFAP-positive astrocytes or in hippocampal neurons. At 1-week and 4-weeks following ADX, we observed a population of large, ameboid, ANX7-immunopositive microglia ("reactive microglia") which were largely confined to the granule cell layer of the dentate gyrus throughout its rostrocaudal extent. No reactive microglia were present in the hippocampus of sham-ADX or ADX + corticosterone treated animals. In 4-weeks ADX animals but not 1-week ADX, ANX7-immunostaining was significantly increased in the mossy fiber layer of CA3, due to the presence of many small, dark-staining "activated microglia". Our results show that ANX7 is abundantly expressed in the rat hippocampus by different microglial forms (e.g., ramified, activated and reactive microglia), suggesting an important role for this calcium-binding protein in microglial Ca2+-dependent processes.}, Author = {Moga, Margaret M. and Dempah, Dominique and Zhou, Dan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Research Support, Non-U.S. Gov't;Rats, Sprague-Dawley;Glial Fibrillary Acidic Protein;Immunohistochemistry;Hippocampus;Comparative Study;Time Factors;Rats;Annexin A7;Microglia;Antigens, CD11b;11 Glia;Animals;Male;Adrenalectomy}, Nlm_Id = {7600130}, Number = {1-2}, Organization = {Department Anatomy and Cell Biology, Indiana University School of Medicine, Terre Haute, IN 47809, USA. mmoga\@medicine.indstate.edu}, Pages = {42-7}, Pii = {S0304-3940(05)00022-4}, Pubmed = {15854748}, Title = {Annexin 7-immunoreactive microglia in the hippocampus of control and adrenalectomized rats}, Uuid = {8FC8F2DD-86CE-45DB-8D05-1563ADC16D78}, Volume = {380}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2005.01.022}} @article{Mohajerani:2007, Abstract = {At early developmental stages, correlated neuronal activity is thought to exert a critical control on functional and structural refinement of synaptic connections. In the hippocampus, between postnatal day 2 (P2) and P6, network-driven giant depolarizing potentials (GDPs) are generated by the synergistic action of glutamate and GABA, which is depolarizing and excitatory. Here the rising phase of GDPs was used to trigger Schaffer collateral stimulation in such a way that synchronized network activity was coincident with presynaptic activation of afferent input. This procedure produced a persistent increase in spontaneous and evoked alpha-amino-3-hydroxy-5-methyl-4-isoxadepropionic acid-mediated glutamatergic currents, an effect that required calcium influx through postsynaptic L-type calcium channels. No potentiation was observed when a delay of 3 sec was introduced between GDPs and afferent stimulation. Pairing-induced potentiation was prevented by scavengers of endogenous BDNF or tropomyosin-related kinase receptor B (TrkB) receptor antagonists. Blocking TrkB receptors in the postsynaptic cell did not prevent the effects of pairing, suggesting that BDNF, possibly secreted from the postsynaptic cell during GDPs, acts on TrkB receptors localized on presynaptic neurons. Application of exogenous BDNF mimicked the effects of pairing on synaptic transmission. In addition, pairing-induced synaptic potentiation was blocked by ERK inhibitors, suggesting that BDNF activates the MAPK/ERK cascade, which may lead to transcriptional regulation and new protein synthesis in the postsynaptic neuron. These results support the hypothesis that, during a critical period of postnatal development, GABAA-mediated GDPs are instrumental in tuning excitatory synaptic connections and provide insights into the molecular mechanisms involved in this process.}, Author = {Mohajerani, Majid H. and Sivakumaran, Sudhir and Zacchi, Paola and Aguilera, Pedro and Cherubini, Enrico}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Synapses;research support, non-u.s. gov't;Excitatory Postsynaptic Potentials;21 Neurophysiology;Long-Term Potentiation;Hippocampus;Rats;Calcium;Extracellular Signal-Regulated MAP Kinases;MAP Kinase Signaling System;Rats, Wistar;Brain-Derived Neurotrophic Factor;Animals;Receptors, N-Methyl-D-Aspartate;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {32}, Organization = {Neuroscience Program, International School for Advanced Studies, Beirut 2-4, 34014 Trieste, Italy.}, Pages = {13176-81}, Pii = {0704533104}, Pubmed = {17656555}, Title = {Correlated network activity enhances synaptic efficacy via BDNF and the ERK pathway at immature CA3 CA1 connections in the hippocampus}, Uuid = {1FC0F1BD-5410-432D-A454-92F67FCB5C93}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0704533104}} @article{Mohapel:2005, Abstract = {Hippocampus-mediated learning enhances neurogenesis in the adult dentate gyrus (DG), and this process has been suggested to be involved in memory formation. The hippocampus receives abundant cholinergic innervation and acetylcholine (ACh) plays an important role in learning and Alzheimer's disease (AD) pathophysiology. Here, we show that a selective neurotoxic lesion of forebrain cholinergic input with 192 IgG-saporin reduces DG neurogenesis with a concurrent impairment in spatial memory. Conversely, systemic administration of the cholinergic agonist physostigmine increases DG neurogenesis. We find that changes of forebrain ACh levels primarily influence the proliferation and/or the short-term survival rather than the long-term survival or differentiation of the new neurons. We further demonstrate that these newly born cells express the muscarinic receptor subtypes M1 and M4. Our data provide evidence that forebrain ACh promotes neurogenesis, and suggest that the impaired cholinergic function in AD may in part contribute to deficits in learning and memory through reductions in the formation of new hippocampal neurons.}, Author = {Mohapel, Paul and Leanza, Giampiero and Kokaia, Merab and Lindvall, Olle}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0197-4580}, Journal = {Neurobiol Aging}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {8100437}, Number = {6}, Organization = {Section of Restorative Neurology, Wallenberg Neuroscience Centre, BMC A11, SE-221 84 Lund, Sweden.}, Pages = {939-46}, Pii = {S0197-4580(04)00280-5}, Pubmed = {15718053}, Title = {Forebrain acetylcholine regulates adult hippocampal neurogenesis and learning}, Uuid = {B2F6BF43-0AF7-4595-91D9-43B4094F8609}, Volume = {26}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neurobiolaging.2004.07.015}} @article{Mokeichev:2007, Abstract = {It was recently discovered that subthreshold membrane potential fluctuations of cortical neurons can precisely repeat during spontaneous activity, seconds to minutes apart, both in brain slices and in anesthetized animals. These repeats, also called cortical motifs, were suggested to reflect a replay of sequential neuronal firing patterns. We searched for motifs in spontaneous activity, recorded from the rat barrel cortex and from the cat striate cortex of anesthetized animals, and found numerous repeating patterns of high similarity and repetition rates. To test their significance, various statistics were compared between physiological data and three different types of stochastic surrogate data that preserve dynamical characteristics of the recorded data. We found no evidence for the existence of deterministically generated cortical motifs. Rather, the stochastic properties of cortical motifs suggest that they appear by chance, as a result of the constraints imposed by the coarse dynamics of subthreshold ongoing activity.}, Author = {Mokeichev, Alik and Okun, Michael and Barak, Omri and Katz, Yonatan and Ben-Shahar, Ohad and Lampl, Ilan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Visual Cortex;24 Pubmed search results 2008;research support, non-u.s. gov't;21 Neurophysiology;Cats;Rats;Stochastic Processes;Algorithms;Cell Count;Animals;Patch-Clamp Techniques;Cerebral Cortex;Membrane Potentials;Neurons}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel.}, Pages = {413-25}, Pii = {S0896-6273(07)00037-2}, Pubmed = {17270737}, Title = {Stochastic emergence of repeating cortical motifs in spontaneous membrane potential fluctuations in vivo}, Uuid = {5D3F6844-FE3C-40DA-8403-15CC9BD99587}, Volume = {53}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.01.017}} @article{Molnar:2006, Abstract = {Donald Hebb postulated the existence of a mechanism of activity-dependent transcription and synaptic modification almost 60 years ago. While the details of this process are still unclear, a new study by Ince-Dunn et al. in this issue of Neuron indicates that NeuroD2, a calcium-regulated transcription factor, plays a central role in thalamocortical synaptic maturation.}, Author = {Moln{\'a}r, Zolt{\'a}n and Moln{\'a}r, Elek}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Models, Biological;10 Development;Basic Helix-Loop-Helix Transcription Factors;Neural Pathways;Neuropeptides;Calcium;comment;Somatosensory Cortex;Animals;Mice;Thalamus;10 Structural plasticity;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Physiology, Anatomy and Genetics, Le Gros Clark Building, University of Oxford, Oxford, OX1 3QX, United Kingdom.}, Pages = {639-42}, Pii = {S0896-6273(06)00129-2}, Pubmed = {16504936}, Title = {Calcium and NeuroD2 control the development of thalamocortical communication}, Uuid = {AC14514F-3890-4541-A1D8-61BDA6639417}, Volume = {49}, Year = {2006}, url = {papers/Molnár_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.02.012}} @article{Molofsky:2003, Abstract = {Stem cells persist throughout life by self-renewing in numerous tissues including the central and peripheral nervous systems. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects. Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16Ink4a is upregulated in neural stem cells, reducing the rate of proliferation. p16Ink4a deficiency partially reverses the self-renewal defect in Bmi-1-/- neural stem cells. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16Ink4a expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues. 1476-4687 Journal Article}, Author = {Molofsky, A. V. and Pardal, R. and Iwashita, T. and Park, I. K. and Clarke, M. F. and Morrison, S. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {Nature}, Keywords = {Cell Survival;Cell Differentiation;Animals;Protein p16/metabolism;Apoptosis;Stem Cells/*cytology/*metabolism;Mice, Inbred C57BL;Support, Non-U.S. Gov't;Cell Lineage;Neural Crest/cytology/metabolism;Proto-Oncogene Proteins/deficiency/genetics/*metabolism;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Neurons/*cytology/*metabolism;C pdf;Nuclear Proteins/deficiency/genetics/*metabolism;Nervous System/*cytology/*metabolism}, Number = {6961}, Organization = {Howard Hughes Medical Institute, and Departments of Internal Medicine and Cell and Developmental Biology, University of Michigan, Ann Arbor, Michigan 48109-0934, USA.}, Pages = {962-7}, Pubmed = {14574365}, Title = {Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation}, Uuid = {4DA326E9-F3C9-40D6-9A96-9A24B6E9F11D}, Volume = {425}, Year = {2003}, url = {papers/Molofsky_Nature2003.pdf}} @article{Mombaerts:2006, Abstract = {The main olfactory epithelium of the mouse is a mosaic of 2000 populations of olfactory sensory neurons (OSNs). Each population expresses one allele of one of the 1000 intact odorant receptor (OR) genes. An OSN projects a single unbranched axon to a single glomerulus, from an array of 1600-1800 glomeruli in the main olfactory bulb. Within a glomerulus the OSN axon synapses with the dendrites of second-order neurons and interneurons. Axons of OSNs that express the same OR project to the same glomeruli-typically one glomerulus per half-bulb and thus four glomeruli per mouse. These glomeruli are located at characteristic positions within the glomerular layer of the bulb. ORs determine both the odorant response profile of the OSN and the projection of its axon to a specific glomerulus. I focus on genetic approaches to the axonal wiring problem, particularly on how ORs may function in axonal wiring.}, Author = {Mombaerts, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1081-0706}, Journal = {Annu Rev Cell Dev Biol}, Keywords = {13 Olfactory bulb anatomy;24 Pubmed search results 2008;Olfactory Pathways;Evolution, Molecular;Receptors, Adrenergic, beta-2;Ephrins;Animals;Mice;Receptors, Odorant;review;Axons}, Nlm_Id = {9600627}, Organization = {Rockefeller University, New York, New York 10021, USA. peter\@rockefeller.edu}, Pages = {713-37}, Pubmed = {17029582}, Title = {Axonal wiring in the mouse olfactory system}, Uuid = {6905C562-C088-416F-A8A1-80AEEE33FFCF}, Volume = {22}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.cellbio.21.012804.093915}} @article{Mombaerts:2001, Abstract = {The mouse's sense of smell is built of approximately 1000 input channels. Each of these consists of a population of olfactory sensory neurons that express the same odorant receptor gene and project their axons to the same targets (glomeruli) in the olfactory bulb. A neuron must choose to express a singular receptor gene from a repertoire of approximately 1000 genes, and its axon must be wired to the corresponding glomerulus, from an array of approximately 1800 glomeruli. Genetic experiments have shown that the expressed odorant receptor specifies axonal choice of the innervated glomerulus, but it is not the only determinant. The mechanisms of odorant receptor gene choice and axonal wiring are central to the functional organization of the mammalian olfactory system. Although principles have emerged, our understanding of these processes is still limited.}, Author = {Mombaerts, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:54 -0400}, Journal = {Nat Neurosci}, Keywords = {13 Olfactory bulb anatomy;I both}, Organization = {The Rockefeller University, 1230 York Avenue, New York, New York 10021, USA.}, Pages = {1192-8.}, Title = {How smell develops}, Uuid = {719E6FCE-B0F0-49C2-88C0-82479E0D1C03}, Volume = {4 Supp 1}, Year = {2001}, url = {papers/Mombaerts_NatNeurosci2001.pdf}} @article{Monckton:1980, Abstract = {Several B-lymphocyte mitogens have been previously characterized as efficient inducers of endogenous C-type viruses in mouse spleen cell cultures. We now report that foetal calf serum is also capable of inducing C-type virus release in such cultures. While virus induction by B-cell mitogens was found to be serum independent, the combined effects of serum and mitogens were found to be additive and, with some serum batches, synergistic. The kinetics of induction of virus release by serum was very similar to the established pattern using mitogens. The effect of serum was concentration-dependent. The serum lipoprotein fraction prepared by density ultracentrifugation contained virus-inducing activity. By co-cultivation with mink CCL64 cells, stable lines of mouse xenotropic C-type virus could be recovered from cultures which contained serum, serum lipoprotein fraction or mitogens, but not from control cultures. Preliminary evidence indicates that human sera contained a similar virus-inducing activity in the lipoprotein fraction.}, Author = {Monckton, R. P. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0022-1317}, Journal = {J Gen Virol}, Keywords = {Lipoproteins;Mice, Inbred BALB C;Blood;Animals;Cells, Cultured;Lymphocytes;Lipopolysaccharides;Mice, Inbred C3H;15 Retrovirus mechanism;RNA-Directed DNA Polymerase;Retroviridae;Mitogens;Virus Activation;Mice;Fetal Blood;24 Pubmed search results 2008;Bromodeoxyuridine;Virus Replication;15 ERVs retroelements;Spleen;Mice, Inbred AKR}, Medline = {80161930}, Month = {3}, Nlm_Id = {0077340}, Number = {1}, Pages = {59-66}, Pubmed = {6154125}, Title = {Foetal calf serum acts as an inducer of endogenous C-type virus in mouse lymphoid cells}, Uuid = {1FE44D3D-5C0D-4DFA-B762-30310693919C}, Volume = {47}, Year = {1980}} @article{Monier:2006, Abstract = {We describe the topographical distribution of microglial subpopulations during development of the human diencephalon and telencephalon. Brains from embryos and fetuses age 5-23.5 gestational weeks (gw) were subjected to single- and double-immunolabeling for lectin RCA-1 (Ricinus Communis Agglutinin 1), Iba1 (a microglial marker), CD68 (specific of macrophages), CD45 (marker for mononucleate cells of hematopoietic lineage), CD34 (expressed on endothelial cells), and MIB1 and Ki67 (markers for cell proliferation). At 5.5 gw the first intracerebral microglial cells were seen close to the meninges and choroid plexus near the di-telencephalic fissure. They were amoeboid and positive for Iba1, CD45, and RCA-1, whereas cells in the deep parenchyma expressed Iba1/CD68/RCA-1 and constituted clusters. In the developing diencephalon, microglial clusters were located in junctional regions of the white matter anlagen, most notably at the junctions of the internal capsule with the thalamic projections, the external capsule, and the cerebral peduncle. In the cortical anlagen, Iba1+/RCA-1/CD68+/CD45+ cells accumulated at 10-12 gw, constituting a tangential band at the junction between the cortical plate and the subplate. Between 10 and 16 gw microglial clusters increased markedly in size and cellular density. Contact between Iba1+ microglia and CD34+ blood vessels was clearly visible from 10-12 gw onward, first in microglial clusters of the white matter anlagen and subsequently throughout the parenchyma. From the middle of the second trimester onward microglial cells colonized the entire cerebral parenchyma, developed a ramified morphology, and downregulated their surface antigens, but remained more numerous in the white matter.}, Author = {Monier, Anne and Evrard, Philippe and Gressens, Pierre and Verney, Catherine}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Embryo;Cell Differentiation;research support, non-u.s. gov't;Fetus;Pregnancy Trimester, Second;Female;Immunohistochemistry;11 Glia;Microglia;Pregnancy;Humans;Brain;Pregnancy Trimester, First;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {0406041}, Number = {4}, Organization = {Inserm, U676, Paris, F-75019 France.}, Pages = {565-82}, Pubmed = {17029271}, Title = {Distribution and differentiation of microglia in the human encephalon during the first two trimesters of gestation}, Uuid = {93B11D64-44E2-4B97-A7EB-058E61C4977C}, Volume = {499}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21123}} @article{Monje:2002, Abstract = {In both pediatric and adult patients, cranial radiation therapy causes a debilitating cognitive decline that is poorly understood and currently untreatable. This decline is characterized by hippocampal dysfunction, and seems to involve a radiation-induced decrease in postnatal hippocampal neurogenesis. Here we show that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitor-cell population. Not only is hippocampal neurogenesis ablated, but the remaining neural precursors adopt glial fates and transplants of non-irradiated neural precursor cells fail to differentiate into neurons in the irradiated hippocampus. The inhibition of neurogenesis is accompanied by marked alterations in the neurogenic microenvironment, including disruption of the microvascular angiogenesis associated with adult neurogenesis and a marked increase in the number and activation status of microglia within the neurogenic zone. These findings provide clear targets for future therapeutic interventions. 1078-8956 Journal Article}, Author = {Monje, M. L. and Mizumatsu, S. and Fike, J. R. and Palmer, T. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {Nat Med}, Keywords = {Cell Differentiation;DNA Repair/radiation effects;Animals;Cells, Cultured;Microglia/radiation effects;Rats;Cell Division/radiation effects;Stem Cell Transplantation;Female;Bromodeoxyuridine/analysis/metabolism;D pdf;Stem Cells/*radiation effects;Neovascularization, Pathologic;Rats, Inbred F344;Support, Non-U.S. Gov't;06 Adult neurogenesis injury induced;Cell Transplantation;Astrocytes/radiation effects;Neurons/*radiation effects;Support, U.S. Gov't, P.H.S.;Brain/*pathology/*radiation effects}, Number = {9}, Organization = {Department of Neurosurgery, Stanford University, Stanford, California, USA.}, Pages = {955-62}, Title = {Irradiation induces neural precursor-cell dysfunction}, Uuid = {5405B9C8-D938-407C-9285-2701474788BF}, Volume = {8}, Year = {2002}, url = {papers/Monje_NatMed2002.pdf}} @article{Monsonego:2003, Abstract = {Although neurodegenerative diseases such as Alzheimer's disease are not classically considered mediated by inflammation or the immune system, in some instances the immune system may play an important role in the degenerative process. Furthermore, it has become clear that the immune system itself may have beneficial effects in nervous system diseases considered neurodegenerative. Immunotherapeutic approaches designed to induce a humoral immune response have recently been developed for the treatment of Alzheimer's disease. These studies have led to human trials that resulted in both beneficial and adverse effects. In animal models, it has also been shown that immunotherapy designed to induce a cellular immune response may be of benefit in central nervous system injury, although T cells may have either a beneficial or detrimental effect depending on the type of T cell response induced. These areas provide a new avenue for exploring immune system-based therapy of neurodegenerative diseases and will be discussed here with a primary focus on Alzheimer's disease. We will also discuss how these approaches affect microglia activation, which plays a key role in therapy of such diseases.}, Author = {Monsonego, Alon and Weiner, Howard L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:54 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Immunotherapy;T-Lymphocytes;Human;Animals;Antigen-Presenting Cells;Amyloid beta-Protein;review, tutorial;Alzheimer Vaccines;review;Microglia;Antibody Formation;Lymphocyte Activation;21 Neurodegenerative;Clinical Trials;Alzheimer Disease;21 Neurophysiology;Immunization;Immunity, Mucosal;Immunity, Natural;Central Nervous System;Nitric Oxide}, Medline = {22954848}, Month = {10}, Nlm_Id = {0404511}, Number = {5646}, Organization = {Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. amonsonego\@rics.bwh.harvard.edu}, Pages = {834-8}, Pii = {302/5646/834}, Pubmed = {14593170}, Title = {Immunotherapeutic approaches to Alzheimer's disease}, Uuid = {4193E8A4-1F11-41AD-B948-B2ACE071736F}, Volume = {302}, Year = {2003}, url = {papers/Monsonego_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1088469}} @article{Montague:1999, Abstract = {The subcellular localization of ionotropic glutamate receptor (GluR) subunits was examined with light and electron microscopy in the rat olfactory bulb by using antibodies to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunits: GluR1, GluR2/3, and GluR4; and kainate (KA) receptor subunits: GluR5/6/7. Immunoreactivity to GluR1 was heavy in the glomerular layer, moderate in the external plexiform layer, and localized to periglomerular somata and dendrites, short axon somata and dendrites, mitral cell somata, and mitral/tufted dendrites. GluR2/3 immunoreactivity was heavy in the external plexiform and glomerular layers and localized to periglomerular somata and dendrites, mitral cell somata, mitral/tufted dendrites, granule cell somata, and olfactory nerve-associated glia. GluR4 immunoreactivity showed heavy staining in the external plexiform and olfactory nerve layers with localization to mitral cells, mitral/tufted dendritic processes, and olfactory nerve glial processes. GluR5/6/7 immunoreactivity was heavy in the external plexiform layer, moderate in the olfactory nerve and glomerular layers, and localized to granule cells, mitral cells, and mitral/tufted dendritic processes. Ultrastructural immunolabeling for all antibodies examined showed immunoreactivity in the postsynaptic membrane and densities, adjacent dendritic cytoplasm, and somatic cytoplasm. These data demonstrate a highly specific laminar, cellular, and subcellular distribution of ionotropic GluR subunits within the primary afferent and local synaptic circuits of the olfactory bulb. The results are consistent with the notion that the different roles subserved by glutamate in the olfactory bulb are actuated, in part, by a differential distribution of GluR subunits. 99146417 0021-9967 Journal Article}, Author = {Montague, A. A. and Greer, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Comp Neurol}, Keywords = {Receptors, Kainic Acid/*chemistry;Rats, Sprague-Dawley;Subcellular Fractions/*chemistry;Olfactory Bulb/*chemistry;Comparative Study;I-5;Microscopy, Electron;Rats;Animal;Support, U.S. Gov't, P.H.S.;Receptors, AMPA/*chemistry;Peptide Fragments/*analysis;13 Olfactory bulb anatomy}, Number = {2}, Organization = {Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.}, Pages = {233-46}, Pubmed = {10023812}, Title = {Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb}, Uuid = {49A6850F-27D2-44FF-94EC-17DE05D0F9C5}, Volume = {405}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10023812}} @article{Montgomery:2008, Abstract = {Rapid eye movement (REM) sleep has been considered a paradoxical state because, despite the high behavioral threshold to arousing perturbations, gross physiological patterns in the forebrain resemble those of waking states. To understand how intrahippocampal networks interact during REM sleep, we used 96 site silicon probes to record from different hippocampal subregions and compared the patterns of activity during waking exploration and REM sleep. Dentate/CA3 theta and gamma synchrony was significantly higher during REM sleep compared with active waking. In contrast, gamma power in CA1 and CA3-CA1 gamma coherence showed significant decreases in REM sleep. Changes in unit firing rhythmicity and unit-field coherence specified the local generation of these patterns. Although these patterns of hippocampal network coordination characterized the more common tonic periods of REM sleep (approximately 95\%of total REM), we also detected large phasic bursts of local field potential power in the dentate molecular layer that were accompanied by transient increases in the firing of dentate and CA1 neurons. In contrast to tonic REM periods, phasic REM epochs were characterized by higher theta and gamma synchrony among the dentate, CA3, and CA1 regions. These data suggest enhanced dentate processing, but limited CA3-CA1 coordination during tonic REM sleep. In contrast, phasic bursts of activity during REM sleep may provide windows of opportunity to synchronize the hippocampal trisynaptic loop and increase output to cortical targets. We hypothesize that tonic REM sleep may support off-line mnemonic processing, whereas phasic bursts of activity during REM may promote memory consolidation.}, Author = {Montgomery, Sean M. and Sirota, Anton and Buzs{\'a}ki, Gy{\"o}rgy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Motor Activity;Wakefulness;Rats, Long-Evans;Animals;Sleep, REM;Theta Rhythm;Rats;Neural Pathways;Synaptic Transmission;Exploratory Behavior;Hippocampus;Pyramidal Cells;Biological Clocks;research support, non-u.s. gov't;Male;Nerve Net;Action Potentials;Learning;Neurons;Dentate Gyrus;research support, n.i.h., extramural;Maze Learning;24 Pubmed search results 2008;research support, u.s. gov't, non-p.h.s.}, Month = {6}, Nlm_Id = {8102140}, Number = {26}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA.}, Pages = {6731-41}, Pii = {28/26/6731}, Pubmed = {18579747}, Title = {Theta and gamma coordination of hippocampal networks during waking and rapid eye movement sleep}, Uuid = {A6283407-78A4-4D17-A50C-2319F3CC68AE}, Volume = {28}, Year = {2008}, url = {papers/Montgomery_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1227-08.2008}} @article{Monuki:2001, Abstract = {All the higher mental and cognitive functions unique to humans depend on the neocortex ('new' cortex, referring to its relatively recent appearance in evolution), which is divided into discrete areas that subserve distinct functions, such as language, movement and sensation. With a few notable exceptions, all neocortical areas have six layers of neurons and a remarkably similar thickness and overall cell density, despite subtle differences in their cellular architecture. Furthermore, all neocortical areas are formed over roughly the same time period during development and provide little hint at early developmental stages of the rich functional diversity that becomes apparent as development comes to an end. How these areas are formed has long fascinated developmental neuroscientists, because the formation of new cortical areas, with the attendant appearance of new cortical functions, is what must have driven the evolution of mammalian behavior.}, Author = {Monuki, E. S. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:54 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Mice;10 Development;Human;Mammals;Stem Cells;Neocortex;Embryonic Induction;Body Patterning;Support, U.S. Gov't, P.H.S.;review, tutorial;Animals;Support, Non-U.S. Gov't;Nervous System Malformations;Nerve Growth Factors;review}, Medline = {21547544}, Month = {11}, Nlm_Id = {9809671}, Organization = {Division of Neurogenetics, Beth Israel Deaconess Medical Center, and Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA. esmonuki\@alum.mit.edu}, Pages = {1199-206}, Pii = {nn752}, Pubmed = {11687830}, Title = {Mechanisms of cerebral cortical patterning in mice and humans}, Uuid = {0112C0B9-8615-4892-AA9D-7C608E629398}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Monuki_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn752}} @article{Monuki:2001a, Abstract = {The organizing centers and molecules that pattern the cerebral cortex have been elusive. Here we show that cortical patterning involves regulation of the Lhx2 homeobox gene by the roof plate. Roof plate ablation results in reduced cortical size and Lhx2 expression defects that implicate roof plate signals in the bimodal regulation of Lhx2 in vivo. Bimodal Lhx2 regulation can be recapitulated in explants using two roof plate-derived signaling molecules, Bmp4 and Bmp2. Loss of Lhx2 function results in profound losses of cortical progenitors and neurons, but Lhx2 mutants continue to generate cortical neurons from dorsal sources that may include the roof plate region itself. These findings provide evidence for the roof plate as an organizing center of the developing cortex and for a roof plate-Lhx2 pathway in cortical patterning.}, Author = {Monuki, E. S. and Porter, F. D. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;10 Hippocampus;Animals;Transcription Factors;Cells, Cultured;Gene Expression Regulation, Developmental;Pregnancy;Transforming Growth Factor beta;Female;Homeodomain Proteins;Bone Morphogenetic Proteins;Male;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;Mice, Knockout;Neurons;Cerebral Cortex;Mice;Growth Substances;Research Support, Non-U.S. Gov't}, Medline = {21576527}, Month = {11}, Nlm_Id = {8809320}, Number = {4}, Organization = {Division of Neurogenetics, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.}, Pages = {591-604}, Pii = {S0896-6273(01)00504-9}, Pubmed = {11719201}, Title = {Patterning of the dorsal telencephalon and cerebral cortex by a roof plate-Lhx2 pathway}, Uuid = {0530A234-C1AB-4FC9-B071-BF3BAD333AF5}, Volume = {32}, Year = {2001}} @article{Monyer:2004, Abstract = {Structural and functional diversity of GABAergic interneurons has become increasingly central in our understanding of the elemental steps of information processing in the brain. The use of different molecular, electrophysiological and anatomical techniques has provided a wealth of new information regarding GABAergic interneurons over the past decade but it has also led to confusion regarding the number of subtypes of GABAergic interneurons. Combinatorial approaches that also consider multiple parameters seem now to offer renewed hope for finally clarifying the structural diversity of GABAergic interneurons. New molecular techniques have become a powerful tool for exposing the functional diversity of GABAergic neurons at the cellular, microcircuit and systems levels. This article reviews literature regarding molecular tools that have been used, or that appear promising for future attempts, to classify GABAergic interneurons. Some important limitations will also be indicated.}, Author = {Monyer, Hannah and Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {24 Pubmed search results 2008;21 Neurophysiology;Reverse Transcriptase Polymerase Chain Reaction;Mental Processes;Animals, Genetically Modified;Gene Expression Regulation;Interneurons;gamma-Aminobutyric Acid;Animals;Humans;Mice;review;RNA, Messenger}, Month = {2}, Nlm_Id = {7808616}, Number = {2}, Organization = {IZN, Department of Clinical Neurobiology, University of Heidelberg, Heidelberg, Germany. monyer\@urz.uni-hd.de}, Pages = {90-7}, Pii = {S0166223603004090}, Pubmed = {15102488}, Title = {Interneuron Diversity series: Molecular and genetic tools to study GABAergic interneuron diversity and function}, Uuid = {A1CEDBC7-7A37-4EDF-91A2-26793A08FE91}, Volume = {27}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2003.12.008}} @article{Moody:1998, Abstract = {Electrical activity participates in the development of the nervous system and comes in two general forms. Use-dependent or experience-driven activity occurs relatively late in development, and is important in events of terminal nervous system differentiation, such as stabilization of synaptic connections. Earlier in development, activity is spontaneous, occurring independently of normal sensory input and motor output. Spontaneous activity participates in many of the initial events of axon outgrowth, pruning of synaptic connections, and maturation of neuronal signaling properties. Despite its importance, the genesis of spontaneous activity is poorly understood. What is clear is that spontaneous activity must be regulated by the patterns with which voltage- and ligand-gated ion channels develop in individual neurons. This review explores how that regulation most likely occurs.}, Author = {Moody, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Muscles;Ion Channels;21 Neurophysiology;Action Potentials;21 Circuit structure-function;Nervous System;Calcium Signaling;Animals;21 Cortical oscillations;24 Pubmed search results 2008;Neurons;review}, Month = {10}, Nlm_Id = {0213640}, Number = {1}, Organization = {Department of Zoology, University of Washington, Seattle 98195-1800, USA.}, Pages = {97-109}, Pii = {10.1002/(SICI)1097-4695(199810)37:1<97::AID-NEU8>3.0.CO;2-3}, Pubmed = {9777735}, Title = {Control of spontaneous activity during development}, Uuid = {75FDFAC8-E32B-431F-867E-880893320408}, Volume = {37}, Year = {1998}} @article{Moody:2005, Abstract = {At specific stages of development, nerve and muscle cells generate spontaneous electrical activity that is required for normal maturation of intrinsic excitability and synaptic connectivity. The patterns of this spontaneous activity are not simply immature versions of the mature activity, but rather are highly specialized to initiate and control many aspects of neuronal development. The configuration of voltage- and ligand-gated ion channels that are expressed early in development regulate the timing and waveform of this activity. They also regulate Ca2+ influx during spontaneous activity, which is the first step in triggering activity-dependent developmental programs. For these reasons, the properties of voltage- and ligand-gated ion channels expressed by developing neurons and muscle cells often differ markedly from those of adult cells. When viewed from this perspective, the reasons for complex patterns of ion channel emergence and regression during development become much clearer.}, Author = {Moody, William J. and Bosma, Martha M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0031-9333}, Journal = {Physiol Rev}, Keywords = {Ion Channel Gating;Neurons;Ion Channels;Muscles;Ligands;21 Neurophysiology;Circuit structure-function;Animals;Brain;Humans;review;Muscle, Skeletal;Spontaneous activity;experience dependent plasticity;development;connectivity;10 circuit formation}, Month = {7}, Nlm_Id = {0231714}, Number = {3}, Organization = {Department of Biology, University of Washington, Seattle, Washington 98195, USA. profbill\@u.washington.edu}, Pages = {883-941}, Pii = {85/3/883}, Pubmed = {15987798}, Title = {Ion channel development, spontaneous activity, and activity-dependent development in nerve and muscle cells}, Uuid = {B485BCD7-42B0-4239-9508-37D422BACDEB}, Volume = {85}, Year = {2005}, url = {papers/Moody_PhysiolRev2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/physrev.00017.2004}} @article{Mooney:2004, Abstract = {Abnormalities in the migration of cortical neurons to ectopic sites can be caused by prenatal exposure to ethanol. In extreme cases, cells migrate past the pial surface and form suprapial heterotopias or 'warts'. We used organotypic slice cultures from 17-day-old rat fetuses to examine structural and molecular changes that accompany wart formation. Cultures were exposed to ethanol (0, 200, 400 or 800 mg/dl) and maintained for 2-32 h. Fixed slices were sectioned and immunolabeled with antibodies directed against calretinin, reelin, nestin, GFAP, doublecortin, MAP-2 and NeuN. Ethanol promoted the widespread infiltration of the marginal zone (MZ) with neurons and the focal formation of warts. The appearance of warts is time- and concentration-dependent. Heterotopias comprised migrating neurons and were not detected in control slices. Warts were associated with breaches in the array of Cajal-Retzius cells and with translocation of reelin-immunoexpression from the MZ to the outer limit of the wart. Ethanol also altered the morphology of the radial glia. Thus, damage to the integrity of superficial cortex allows neurons to infiltrate the MZ, and if the pial-subpial glial barrier is also compromised these ectopic neurons can move beyond the normal cerebral limit to form a wart.}, Author = {Mooney, Sandra M. and Siegenthaler, Julie A. and Miller, Michael W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Embryo;10 Development;Female;Rats;Dose-Response Relationship, Drug;Choristoma;Ethanol;Support, U.S. Gov't, Non-P.H.S.;Pregnancy;Support, U.S. Gov't, P.H.S.;Organ Culture;Animals;Cerebral Cortex}, Month = {10}, Nlm_Id = {9110718}, Number = {10}, Organization = {Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.}, Pages = {1071-80}, Pii = {bhh066}, Pubmed = {15166098}, Title = {Ethanol induces heterotopias in organotypic cultures of rat cerebral cortex}, Uuid = {1D5B2D88-95BD-4629-BE3E-F411E892C3FB}, Volume = {14}, Year = {2004}, url = {papers/Mooney_CerebCortex2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh066}} @article{Moore:2002, Abstract = {The repair of oxidative DNA lesions (ODLs) in the nucleus of ischemic cortical brain cells was examined following experimentally induced stroke by occluding the right middle cerebral artery and both common carotid arteries for 60-90 min followed by reperfusion in male long-Evans hooded rats. The control group consisted of sham-operated animals undergoing the same surgery without vessel occlusion. Using a gene-specific assay based upon the presence of Escherichia coli Fpg protein-sensitive sites, we noted that animals with stroke exhibited six and four ODLs per gene in the actin and DNA polymerase-beta genes, respectively. This was increased from one per four copies of each gene in the sham-operated control (p <0.01). One half of the initial ODLs was repaired within 30 min, and 83\%of them were repaired as early as 45 min of reperfusion. There was no further increase when gene repair was measured again at 2 h of reperfusion. The rates of active repair within 45 min of reperfusion were the same in these two genes (p = 0.103, ANOVA). BrdU (10 mg/kg) was administered via intraperitoneal injection at least one day before surgery. We observed that there was no significant incorporation of BrdU triphosphates into genomic DNA during active repair, but there were significant amounts of BrdU triphosphate in nuclear DNA after active repair. The result indicates that genomic repair of ODLs in the brain did not significantly incorporate BrdU, and the initiation of neurogenesis probably starts after the completion of repair in the brain. 0022-3042 Journal Article}, Author = {Moore, N. and Okocha, F. and Cui, J. K. and Liu, P. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Journal = {J Neurochem}, Keywords = {DNA/metabolism;EE pdf;Cerebrovascular Accident/*genetics;Brain/*physiopathology/surgery;Rats, Long-Evans;Rats;Bromodeoxyuridine/metabolism;Sutures;*DNA Repair;Cell Nucleus/*physiology;Support, U.S. Gov't, P.H.S.;Animals;Male;Brain Injuries/etiology/metabolism}, Number = {1}, Organization = {Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.}, Pages = {111-8}, Title = {Homogeneous repair of nuclear genes after experimental stroke}, Uuid = {F865814F-CDF0-11D9-B244-000D9346EC2A}, Volume = {80}, Year = {2002}, url = {papers/Moore_JNeurochem2002.pdf}} @article{Moore:1999, Abstract = {Recently, the study of sensory cortex has focused on the context-dependent evolution of receptive fields and cortical maps over millisecond to second time-scales. This article reviews advances in our understanding of these processes in the rat primary somatosensory cortex (SI). Subthreshold input to individual rat SI neurons is extensive, spanning several vibrissae from the center of the receptive field, and arrives within 25 ms of vibrissa deflection. These large subthreshold receptive fields provide a broad substrate for rapid excitatory and inhibitory multi-vibrissa interactions. The 'whisking' behavior, an approximately 8 Hz ellipsoid movement of the vibrissae, introduces a context-dependent change in the pattern of vibrissa movement during tactile exploration. Stimulation of vibrissae over this frequency range modulates the pattern of activity in thalamic and cortical neurons, and, at the level of the cortical map, focuses the extent of the vibrissa representation relative to lower frequency stimulation (1 Hz). These findings suggest that one function of whisking is to reset cortical organization to improve tactile discrimination. Recent discoveries in primary visual cortex (VI) demonstrate parallel non-linearities in center-surround interactions in rat SI and VI, and provide a model for the rapid integration of multi-vibrissa input. The studies discussed in this article suggest that, despite its original conception as a uniquely segregated cortex, rat SI has a wide array of dynamic interactions, and that the study of this region will provide insight into the general mechanisms of cortical dynamics engaged by sensory systems.}, Author = {Moore, C. I. and Nelson, S. B. and Sur, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {24 Pubmed search results 2008;21 Neurophysiology;Rats;Motor Activity;Somatosensory Cortex;Animals;Perception;Vibrissae;Neurons;review}, Month = {11}, Nlm_Id = {7808616}, Number = {11}, Organization = {Dept of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, Pages = {513-20}, Pii = {S0166-2236(99)01452-6}, Pubmed = {10529819}, Title = {Dynamics of neuronal processing in rat somatosensory cortex}, Uuid = {73EADF15-9BD0-4509-98E2-341F9B31A90D}, Volume = {22}, Year = {1999}} @article{Moran:2004a, Abstract = {Experimental models such as the facial nerve axotomy paradigm in rodents allow the systematic and detailed study of the response of neurones and their microenvironment to various types of challenges. Well-studied experimental examples include peripheral nerve trauma, the retrograde axonal transport of neurotoxins and locally enhanced inflammation following the induction of experimental autoimmune encephalomyelitis in combination with axotomy. These studies have led to novel insights into the regeneration programme of the motoneurone, the role of microglia and astrocytes in synaptic plasticity and the biology of glial cells. Importantly, many of the findings obtained have proven to be valid in other functional systems and even across species barriers. In particular, microglial expression of major histocompatibility complex molecules has been found to occur in response to various types of neuronal damage and is now regarded as a characteristic component of "glial inflammation". It is found in the context of numerous neurodegenerative disorders including Parkinson's and Alzheimer's disease. The detachment of afferent axonal endings from the surface membrane of regenerating motoneurones and their subsequent displacement by microglia ("synaptic stripping") and long-lasting insulation by astrocytes have also been confirmed in humans. The medical implications of these findings are significant. Also, the facial nerve system of rats and mice has become the best studied and most widely used test system for the evaluation of neurotrophic factors.}, Author = {Moran, Linda B. and Graeber, Manuel B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0165-0173}, Journal = {Brain Res Brain Res Rev}, Keywords = {Nerve Regeneration;Facial Nerve Injuries;11 Glia;review, tutorial;Axotomy;Animals;Disease Models, Animal;review;Humans}, Month = {3}, Nlm_Id = {8908638}, Number = {2-3}, Organization = {Department of Neuropathology, Division of Neuroscience and Psychological Medicine, Faculty of Medicine, Imperial College London, Charing Cross Campus, Fulham Palace Road, London W6 8RF, UK.}, Pages = {154-78}, Pii = {S0165017303002595}, Pubmed = {15003391}, Title = {The facial nerve axotomy model}, Uuid = {FF13CCF2-EE26-11DA-8605-000D9346EC2A}, Volume = {44}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainresrev.2003.11.004}} @article{Moran:2004, Abstract = {This study provides an expression signature of interferon-gamma (IFN-gamma)-activated microglia. Microglia are macrophage precursor cells residing in the brain and spinal cord. The microglial phenotype is highly plastic and changes in response to numerous pathological stimuli. IFN-gamma has been established as a strong immunological activator of microglial cells both in vitro and in vivo. Affymetrix RG\_U34A microarrays were used to determine the effect of IFN-gamma stimulation on migroglia cells isolated from newborn Lewis rat brains. More than 8,000 gene sequences were examined, i.e., 7,000 known genes and 1,000 expressed sequence tag (EST) clusters. Under baseline conditions, microglia expressed 326 of 8,000 genes examined (approximately 4\%of all genes, 182 known and 144 ESTs). Transcription of only 34 of 7,000 known genes and 8 of 1,000 ESTs was induced by IFN-gamma stimulation. The majority of the newly expressed genes encode pro-inflammatory cytokines and components of the MHC-mediated antigen presentation pathway. The expression of 60 of 182 identified genes and of 9 of 144 ESTs was increased by IFN-gamma, whereas 29 of 182 known genes and 7 of 144 ESTs were down-regulated or undetectable in IFN-gamma-stimulated cultures. Overall, the activating effect of IFN-gamma on the microglial transcriptome showed restriction to pathways involved in antigen presentation, protein degradation, actin binding, cell adhesion, apoptosis, and cell signaling. In comparison, down-regulatory effects of IFN-gamma stimulation appeared to be confined to pathways of growth regulation, remodeling of the extracellular matrix, lipid metabolism, and lysosomal processing. In addition, transcriptomic profiling revealed previously unknown microglial genes that were de novo expressed, such as calponin 3, or indicated differential regulatory responses, such as down-regulation of cathepsins that are up-regulated in response to other microglia stimulators.}, Author = {Moran, L. B. and Duke, D. C. and Turkheimer, F. E. and Banati, R. B. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1364-6745}, Journal = {Neurogenetics}, Keywords = {Down-Regulation;Research Support, Non-U.S. Gov't;Rats, Inbred Lew;Rats;Oligonucleotide Array Sequence Analysis;Interferon Type II;Gene Expression;Transcription, Genetic;Up-Regulation;Reproducibility of Results;Microglia;Animals;Antineoplastic Agents;Cells, Cultured;11 Glia}, Month = {6}, Nlm_Id = {9709714}, Number = {2}, Organization = {University Department of Neuropathology, Neurosciences Division, Faculty of Medicine, Imperial College London, London, UK.}, Pages = {95-108}, Pubmed = {15042428}, Title = {Towards a transcriptome definition of microglial cells}, Uuid = {9A72A57B-72B9-4EF4-A20D-46E257DA915E}, Volume = {5}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s10048-004-0172-5}} @article{Mordelet:2002, Abstract = {Transplantation of ex vivo gene-corrected autologous cells represents an attractive therapeutic approach for brain diseases. Among the cells of the central nervous system, brain macrophages are promising candidates due to their role in tissue homeostasis and their implication in several neurological diseases. Up to now, gene transfer into macrophages has proven difficult by most currently available gene delivery methods. We describe herein, an efficient transduction of rat bone marrow-derived and brain macrophages with an HIV-1-derived vector containing a central DNA flap and encoding the GFP reporter gene (TRIP-DeltaU3-GFP). In primary cultures of macrophages our results show that more than 90\%of the cells were transduced by the TRIP vector and that GFP expression remained stable for 1 month without cytopathic effect. In vivo, transplants of transduced macrophages into the striatum of adult rats exhibited long-term expression of GFP up to 3 months. Transduced macrophages were observed around the brain injection site and exhibited the brain macrophage/microglia phenotype. There was no significant sign of astrogliosis around the graft. These results confirm the potential of lentiviral vectors for efficient and stable ex vivo transduction of macrophages. Moreover, transduced autologous macrophages appear as a valuable vehicle for long-term and localized gene expression into the brain.}, Author = {Mordelet, E. and Kissa, K. and Calvo, C-F F. and Lebastard, M. and Milon, G. and van der Werf, S. and Vidal, C. and Charneau, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Transduction, Genetic;HIV-1;Rats, Long-Evans;Astrocytes;Rats;Macrophages;Animals;Brain;Rats, Wistar;11 Glia;Green Fluorescent Proteins;Brain Diseases;Time Factors;Male;Genetic Vectors;Bone Marrow Cells;Gene Therapy;Transplantation, Autologous;Luminescent Proteins;Gene Expression;Cell Death;Research Support, Non-U.S. Gov't}, Medline = {21838676}, Month = {1}, Nlm_Id = {9421525}, Number = {1}, Organization = {Unite de Genetique Moleculaire des Virus Respiratoires, Institut Pasteur, Paris, France.}, Pages = {46-52}, Pubmed = {11850722}, Title = {Brain engraftment of autologous macrophages transduced with a lentiviral flap vector: an approach to complement brain dysfunctions}, Uuid = {A6C77A52-275E-401A-9BC9-EA1789FAA060}, Volume = {9}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301591}} @article{Moreau-Gaudry:2001, Abstract = {Use of oncoretroviral vectors in gene therapy for hemoglobinopathies has been impeded by low titer vectors, genetic instability, and poor expression. Fifteen self- inactivating (SIN) lentiviral vectors using 4 erythroid promoters in combination with 4 erythroid enhancers with or without the woodchuck hepatitis virus postregulatory element (WPRE) were generated using the enhanced green fluorescent protein as a reporter gene. Vectors with high erythroid-specific expression in cell lines were tested in primary human CD34(+) cells and in vivo in the murine bone marrow (BM) transplantation model. Vectors containing the ankyrin-1 promoter showed high-level expression and stable proviral transmission. Two vectors containing the ankyrin-1 promoter and 2 erythroid enhancers (HS-40 plus GATA-1 or HS-40 plus 5-aminolevulinate synthase intron 8 [I8] enhancers) and WPRE expressed at levels higher than the HS2/beta-promoter vector in bulk unilineage erythroid cultures and individual erythroid blast-forming units derived from human BM CD34(+) cells. Sca1(+)/lineage(-) Ly5.1 mouse hematopoietic cells, transduced with these 2 ankyrin-1 promoter vectors, were injected into lethally irradiated Ly5.2 recipients. Eleven weeks after transplantation, high-level expression was seen from both vectors in blood (63\%-89\%of red blood cells) and erythroid cells in BM (70\%-86\%engraftment), compared with negligible expression in myeloid and lymphoid lineages in blood, BM, spleen, and thymus (0\%-4\%). The I8/HS-40-containing vector encoding a hybrid human beta/gamma-globin gene led to 43\%to 113\%human gamma-globin expression/copy of the mouse alpha-globin gene. Thus, modular use of erythroid-specific enhancers/promoters and WPRE in SIN-lentiviral vectors led to identification of high-titer, stably transmitted vectors with high-level erythroid-specific expression for gene therapy of red cell diseases.}, Author = {Moreau-Gaudry, F. and Xia, P. and Jiang, G. and Perelman, N. P. and Bauer, G. and Ellis, J. and Surinya, K. H. and Mavilio, F. and Shen, C. K. and Malik, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Gene Expression;Transduction, Genetic;Animals;Humans;Gene Expression Regulation, Viral;Bone Marrow Transplantation;Comparative Study;Lentivirus;Antigens, CD34;11 Glia;Green Fluorescent Proteins;Enhancer Elements (Genetics);Genetic Vectors;Bone Marrow Cells;RNA Processing, Post-Transcriptional;Hepatitis B Virus, Woodchuck;Mice;Erythroid Progenitor Cells;Luminescent Proteins;Promoter Regions (Genetics);Models, Animal;Gamma-Globulins;Hematopoietic Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {21531304}, Month = {11}, Nlm_Id = {7603509}, Number = {9}, Organization = {Children's Hospital Los Angeles, University of Southern California School of Medicine, Los Angeles 90027, USA.}, Pages = {2664-72}, Pubmed = {11675336}, Title = {High-level erythroid-specific gene expression in primary human and murine hematopoietic cells with self-inactivating lentiviral vectors}, Uuid = {607AA673-A3F0-4F05-AA24-7AAD86A2E836}, Volume = {98}, Year = {2001}} @article{Moreno-Lopez:2000, Abstract = {The subventricular zone (SVZ) of the adult mouse brain retains the capacity to generate new neurons from stem cells. The neuronal precursors migrate tangentially along the rostral migratory stream (RMS) towards the olfactory bulb, where they differentiate as periglomerular and granular interneurons. In this study, we have investigated whether nitric oxide (NO), a signaling molecule in the nervous system with a role in embryonic neurogenesis, may be produced in the proximity of the progenitor cells in the adult brain, as a prerequisite to proposing a functional role for NO in adult neurogenesis. Proliferating and immature precursor cells were identified by immunohistochemistry for bromo-deoxyuridine (BrdU) and PSA-NCAM, respectively, and nitrergic neurons by either NADPH- diaphorase staining or immunohistochemical detection of neuronal NO synthase (NOS I). Nitrergic neurons with long varicose processes were found in the SVZ, intermingled with chains of cells expressing PSA-NCAM or containing BrdU. Neurons with similar characteristics surrounded the RMS all along its caudo-rostral extension as far as the core of the olfactory bulb. No expression of NOS I by precursor cells was detected either in the proliferation or in the migration zones. Within the olfactory bulb, many small cells in the granular layer and around the glomeruli expressed either PSA-NCAM or NOS I and, in some cases, both markers. Colocalization was also found in a few isolated cells at a certain distance from the neurogenesis areas. The anatomical disposition shown indicates that NO may be released close enough to the neuronal progenitors to allow a functional influence of this messenger in adult neurogenesis.}, Author = {Moreno-Lopez, B. and Noval, J. A. and Gonzalez-Bonet, L. G. and Estrada, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Brain Res}, Keywords = {Mice, Inbred Strains;Neural Cell Adhesion Molecules/metabolism;Nitric Oxide/*metabolism;Sialic Acids/metabolism;Cell Differentiation/*physiology;Neurons/cytology/*metabolism;04 Adult neurogenesis factors;Olfactory Bulb/cytology/growth &development/metabolism;Animal;C-14;Stem Cells/cytology/*metabolism;Cell Division/*physiology;Support, Non-U.S. Gov't;Brain/cytology/*growth &development/metabolism;Mice;Male;Cell Movement/physiology}, Number = {1-2}, Organization = {Area de Fisiologia, Facultad de Medicina, Universidad de Cadiz, Plaza Fragela 9, 11003, Cadiz, Spain.}, Pages = {244-50.}, Title = {Morphological bases for a role of nitric oxide in adult neurogenesis}, Uuid = {64C3BA69-EE85-4FE4-AAE3-ABC05CC75703}, Volume = {869}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10865083}} @article{Moreno-Lopez:2004, Abstract = {The subventricular zone of the rodent brain retains the capacity of generating new neurons in adulthood. The newly formed neuroblasts migrate rostrally toward the olfactory bulb, where they differentiate as granular and periglomerular interneurons. The reported presence of differentiated neurons expressing the neuronal isoform of nitric oxide synthase (NOS) in the periphery of the neurogenic region and the organization of their varicose axons as a network in which the precursors are immersed raised the hypothesis that endogenous nitric oxide (NO) may participate in the control of neurogenesis in the subventricular zone. Systemic administration of the NOS inhibitors N(omega)-nitro-L-arginine methyl ester or 7-nitroindazole to adult mice produced a dose- and time-dependent increase in the number of mitotic cells in the subventricular zone, rostral migratory stream, and olfactory bulb, but not in the dentate gyrus of the hippocampus, without affecting apoptosis. In the subventricular zone, this effect was exerted selectively on a precursor subpopulation expressing nestin but not neuronal or glial cell-specific proteins. In addition, in the olfactory bulb, analysis of maturation markers in the newly generated neurons indicated that chronic NOS inhibition caused a delay in neuronal differentiation. Postmitotic cell survival and migration were not affected when NO production was impaired. Our results suggest that NO, produced by nitrergic neurons in the adult mouse subventricular zone and olfactory bulb, exerts a negative control on the size of the undifferentiated precursor pool and promotes neuronal differentiation. 1529-2401 Journal Article}, Author = {Moreno-Lopez, B. and Romero-Grimaldi, C. and Noval, J. A. and Murillo-Carretero, M. and Matarredona, E. R. and Estrada, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Neurosci}, Keywords = {C pdf;04 Adult neurogenesis factors}, Number = {1}, Organization = {Area de Fisiologia, Facultad de Medicina, Universidad de Cadiz, 11003 Cadiz, Spain.}, Pages = {85-95}, Pubmed = {14715941}, Title = {Nitric oxide is a physiological inhibitor of neurogenesis in the adult mouse subventricular zone and olfactory bulb}, Uuid = {6AE54247-7A77-48F2-8C47-05E8E9C56E38}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14715941}} @article{Morgenstern:2003, Abstract = {We have investigated expression of the axon growth-inhibitory proteoglycan NG2 in peripheral nerve. In the adult, NG2 was present on endoneurial and perineurial fibroblasts, but not on Schwann cells. At birth, peripheral nerve NG2 was heavily glycanated, but was much less so in the adult. In vitro, sciatic nerve fibroblasts also produced heavily glycanated NG2. After peripheral nerve injury in rats and humans, an accumulation of NG2-positive cells was observed at the injury site. In the rat, there was an increase in NG2 glycanation for at least 2 weeks following injury. In mixed cultures of Schwann cells and peripheral nerve fibroblasts, the axons preferred to grow on the Schwann cells and seldom crossed onto the fibroblasts. Three-dimensional cultures of sciatic nerve fibroblasts were inhibitory to the growth of dorsal root ganglion axons. Inhibition of proteoglycan synthesis made the cells more permissive. NG2 may play a part in blocking axon regeneration through scar tissue in injured human peripheral nerve. 1044-7431 Journal Article}, Author = {Morgenstern, D. A. and Asher, R. A. and Naidu, M. and Carlstedt, T. and Levine, J. M. and Fawcett, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {G abstr;11 Glia}, Number = {3}, Organization = {Centre for Brain Repair, University of Cambridge, Robinson Way, Cambridge CB2 2PY, UK.}, Pages = {787-802}, Pubmed = {14664826}, Title = {Expression and glycanation of the NG2 proteoglycan in developing, adult, and damaged peripheral nerve}, Uuid = {E565655C-09DD-4E1A-B96B-B2D4EF0D40E7}, Volume = {24}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14664826}} @article{Morilak:1993, Abstract = {Serotonin2 receptors have been implicated in a variety of behavioral and physiological processes, as well as a number of neuropsychiatric disorders. To specify the brain regions and specific cell types possessing serotonin2 receptors, we conducted an immunocytochemical study of the rat brain using a polyclonal serotonin2 receptor antibody. Perfusion-fixed rat brain sections were processed for immunocytochemistry and reactivity was visualized using an immunoperoxidase reaction. Numerous small, round neurons were heavily labeled in the granular and periglomerular regions of the olfactory bulb. Heavy labeling of medium-sized multipolar and bipolar neurons was also seen in olfactory regions of the ventral forebrain, including the anterior olfactory nucleus and olfactory tubercle. Other regions of the basal forebrain exhibiting high levels of immunoreactivity were the nucleus accumbens, ventral pallidum, Islands of Calleja, fundus striatum and endopyriform nucleus. Immunoreactive neurons were also seen in the lateral amygdala. A dense band of small, round cells was stained in layer 2 of pyriform cortex. In neocortex, a very sparse and even distribution of bipolar and multipolar neurons was seen throughout layers II-VI. A much more faintly labeled population of oval cells was observed in the deep layer of retrosplenial and posterior cingulate cortex, and in the granular layer of somatosensory frontoparietal cortex. A moderate number of medium bipolar and multipolar cells were scattered throughout the neostriatum, and a moderate number of pyramidal and pyramidal-like cells were seen in the CA fields of the hippocampus. Diencephalic areas showing immunolabeling included the medial habenula and anterior pretectal nucleus, with less labeling in the ventral lateral geniculate. In the hindbrain, two dense populations of large multipolar cells were heavily labeled in the pedunculopontine and laterodorsal tegmental nuclei, with lesser labeling in the periaqueductal gray, superior colliculus, spinal trigeminal nucleus and nucleus of the solitary tract. Based on the distribution, localization and morphology of immunoreactive neurons in these regions, we hypothesize that subpopulations of serotonin2 containing cells may be GABAergic interneurons or cholinergic neurons. Further, the observed distribution suggests that the physiological effects of serotonin acting through serotonin2 receptors are mediated by a relatively small number of cells in the brain. These observations may have strong functional implications for the pharmacological treatment of certain neuropsychiatric disorders. eng Journal Article}, Author = {Morilak, D. A. and Garlow, S. J. and Ciaranello, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Journal = {Neuroscience}, Keywords = {Prosencephalon/anatomy &histology/cytology/metabolism;Cerebral Cortex/anatomy &histology/cytology/metabolism;13 Olfactory bulb anatomy;Olfactory Bulb/anatomy &histology/cytology/metabolism;Medulla Oblongata/anatomy &histology/cytology/metabolism;Rats;Animal;Neurons/*metabolism;Rats, Sprague-Dawley;Neostriatum/anatomy &histology/cytology/metabolism;Brain/anatomy &histology/*metabolism;Support, Non-U.S. Gov't;Receptors, Serotonin/*biosynthesis/immunology;Diencephalon/anatomy &histology/cytology/metabolism;Support, U.S. Gov't, P.H.S.;Perfusion;Immunohistochemistry;I abstr}, Number = {3}, Organization = {Nancy Pritzker Laboratory of Developmental and Molecular Neurobiology, Department of Psychiatry and Behavioral Sciences, Stanford University, CA 94305-5485.}, Pages = {701-17.}, Title = {Immunocytochemical localization and description of neurons expressing serotonin2 receptors in the rat brain}, Uuid = {0FB24096-79E3-4024-B6F6-604C8134A8BD}, Volume = {54}, Year = {1993}} @article{Morioka:1992, Abstract = {The appearance and cellular distribution of major histocompatibility complex (MHC), as well as lymphocytic and macrophage antigens has been studied in a fully developed experimental rat forebrain glioma. Activated microglial cells and microglia-derived macrophages expressing CR3 complement receptor molecules and MHC class II (Ia) antigen were found throughout the tumor, and with increased density along the tumor's periphery. MHC class I antigen expression was entirely absent from tumor cells, and found only occasionally on microglia. The expression of leukocyte common antigen, and CD4 and CD8 antigens was conspicuous throughout the tumor, and associated with lymphocytes, perivascular cells, and microglia. Cells expressing the ED2 macrophage epitope were almost exclusively of the perivascular type and revealed a distribution dissimilar to that of cells positive for Ia antigen. The ED2 epitope was found sporadically on ramified microglial cells. The results show that despite heavy infiltration with blood mononuclear and CNS microglial cells, the tumor showed no evidence of destruction caused by inflammatory cells. Possible mechanisms of tumor immunosuppressive activity preventing the full immunological activation of microglia and blood mononuclear cells are discussed.}, Author = {Morioka, T. and Baba, T. and Black, K. L. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Neuroglia;Glioma;Rats;Female;Phenotype;Antibodies, Monoclonal;Not relevant;Leukocytes;11 Glia;Nervous System Neoplasms;Neoplasms, Experimental;Animals;Rats, Inbred Strains;Major Histocompatibility Complex;Support, Non-U.S. Gov't}, Medline = {92343307}, Nlm_Id = {0412041}, Number = {6}, Organization = {Department of Neurological Surgery, University of Florida, Gainesville 32610.}, Pages = {590-7}, Pubmed = {1636377}, Title = {Immunophenotypic analysis of infiltrating leukocytes and microglia in an experimental rat glioma}, Uuid = {D8A95923-DBF5-4FD2-AC51-0BB188B8F911}, Volume = {83}, Year = {1992}} @article{Morioka:1992a, Abstract = {We show a differential up-regulation of immunomolecules in the rat dorsal hippocampus accompanying neuronal cell death as a consequence of transient forebrain ischemia (four-vessel occlusion model). Using a panel of monoclonal antibodies (mAbs), we have examined the time course of expression of major histocompatibility complex (MHC) antigens class I (OX-18) and class II (OX-6), leukocyte common antigen (OX-1), CD4 (W3/25) and CD8 (OX-8) antigens, CR3 complement receptor (OX-42), as well as brain macrophage antigen (ED2). The study was performed at time intervals ranging from 1 to 28 days after reperfusion. Throughout all post-ischemic time periods, strongly enhanced immunoreactivity on microglial cells in the CA1 region and dentate hilus and, to a lesser extent, in CA3 was demonstrated with mAb OX-42. MHC class I-positive cells (OX-18) appeared on day 2, whereas cells immunoreactive with OX-1 and W3/25 became evident in the CA1 and hilar regions on post-ischemic day 6. In contrast, MHC class II (Ia) antigen was first detected on indigenous microglia by day 13. In some animals, the OX-8 antibody resulted in the labelling of scattered CD8-positive lymphocytes, but perivascular inflammatory infiltrates were absent. No changes in the expression of ED2 immunoreactivity on perivascular cells could be observed. The results show that following ischemic injury, microglial cells demonstrate a time-dependent up-regulation and de novo expression of certain immunomolecules, indicative of their immunocompetence. The findings are compared with those obtained in other models of brain injury.}, Author = {Morioka, T. and Kalehua, A. N. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Animals;Up-Regulation;Rats;Lymphocytes;Female;Antigens, CD4;Hippocampus;Rats, Inbred Strains;Not relevant;11 Glia;Prosencephalon;Receptors, Complement;Antibodies, Monoclonal;Neuroglia;Antigens, CD8;Support, U.S. Gov't, P.H.S.;Ischemic Attack, Transient;Complement 3;Histocompatibility Antigens Class I;Histocompatibility Antigens Class II}, Medline = {92214062}, Nlm_Id = {0412041}, Number = {2}, Organization = {Department of Neurological Surgery, University of Florida Health Science Center, Gainesville 32610-0244.}, Pages = {149-57}, Pubmed = {1557947}, Title = {Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischemia}, Uuid = {E4528A1F-2BD8-4B6B-8E3F-257B6415B852}, Volume = {83}, Year = {1992}} @article{Morioka:1992b, Abstract = {The response of indigenous CNS microglia to an experimentally induced glioma has been studied in rat brain using lectin histochemistry with the Griffonia simplicifolia B4-isolectin. The study was undertaken 2 weeks after tumor cell injection when tumor size was near maximal. Reactive microglial cells formed a dense band that surrounded most of the well-circumscribed tumor mass, and extended along the corpus callosum into the contralateral cerebral hemisphere. From the periphery inward, reactive microglia extended into the tumor tissue, where large numbers of them were found to be present as microglia-derived macrophages. The lectin stain, which also labels endothelial cells, revealed a highly vascularized tumor with ongoing neovascularization apparent as vascular sprouts. Moderate numbers of lectin-stained blood monocytes were localized primarily inside the vessel lumina. Our results show that microglial cells react to brain tumors; however, it remains to be determined whether the microglial response represents an active antitumor defense mechanism that could be manipulated during immunotherapeutic approaches.}, Author = {Morioka, T. and Baba, T. and Black, K. L. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Neuroglia;Glioma;Rats;Lectins;Not relevant;Transplantation, Homologous;11 Glia;Neoplasm Transplantation;Brain Neoplasms;Histocytochemistry;Support, Non-U.S. Gov't;Horseradish Peroxidase;Animals}, Medline = {92380742}, Nlm_Id = {8806785}, Number = {1}, Organization = {Department of Neurological Surgery, University of Florida, Gainesville 32610.}, Pages = {75-9}, Pubmed = {1387388}, Title = {Response of microglial cells to experimental rat glioma}, Uuid = {77A3B746-7632-42A0-B88D-899C84913AF0}, Volume = {6}, Year = {1992}} @article{Morioka:1991, Abstract = {We have examined the distribution and time course of the microglial reaction in the rat dorsal hippocampus after 25-min transient forebrain ischemia (four-vessel occlusion model). Microglial cells were visualized in brain sections using lectin staining with the Griffonia simplicifolia B4-isolectin following intervals of reperfusion ranging from 20 min to 4 weeks. Increased staining of microglial cells was detected in the dentate hilus and area CA1 as early as 20 min after reperfusion. These same regions demonstrated more intense microglial staining after 24 h. The strongest microglial reaction was observed 4-6 days after reperfusion when reactive microglia were abundant throughout all laminae of CA1 and the dentate hilus. Following longer reperfusion intervals, the microglial reaction became less intense; however, it remained above normal levels until the end of the fourth week. At all time points examined, microglial reactivity in the CA3 pyramidal and dentate granule cell layers was considerably lower than that observed in CA1 and dentate hilus. Our results are consistent with the known serial pathological changes associated with cerebral ischemia, but, in addition, show that the examination of the microglial reaction provides an extremely sensitive indicator of subtle and morphologically nonapparent neuronal damage during the early stages of injury.}, Author = {Morioka, T. and Kalehua, A. N. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0271-678X}, Journal = {J Cereb Blood Flow Metab}, Keywords = {Staining and Labeling;Neuroglia;Female;Lectins;Hippocampus;Time Factors;Not relevant;Rats;11 Glia;Support, U.S. Gov't, P.H.S.;Cell Death;Prosencephalon;Animals;Rats, Inbred Strains;Ischemic Attack, Transient;Neurons}, Medline = {92042381}, Month = {11}, Nlm_Id = {8112566}, Number = {6}, Organization = {Department of Neurological Surgery, University of Florida, Gainesville 32610.}, Pages = {966-73}, Pubmed = {1719009}, Title = {The microglial reaction in the rat dorsal hippocampus following transient forebrain ischemia}, Uuid = {4B59A5F0-5EF3-4B40-A5DA-75A182A19EF6}, Volume = {11}, Year = {1991}} @article{Morioka:1993, Abstract = {We have studied the microglial reaction that accompanies cortical infarction induced by middle cerebral artery occlusion (MCAO). Lectin histochemistry with the B4-isolectin from Griffonia simplicifolia as well as immunocytochemistry with a panel of monoclonal antibodies directed against major histocompatibility complex (MHC) and lymphocytic antigens were performed. Principal attention was focused on neocortical and thalamic regions, representative of primary and secondary ischemic damage, respectively. With the lectin procedure, activated microglial cells were abundant in the neocortex 24 hours after MCAO. In contrast, microglial activation in the thalamus was not apparent until day 2 after MCAO. On day 5, MHC class II antigen was expressed by reactive microglia in fiber tracts traversing the striatum, but was absent from activated microglia in the primary cortical infarction area. MHC class I and lymphocytic antigens were expressed differentially on microglia with class I antigens appearing early and lymphocytic antigens appearing late in the time course after focal ischemia. The findings are compatible with previous studies during global ischemia and confirm the early activation and the progressive nature of immunomolecule expression on activated microglia after an ischemic insult. In addition to neocortical and thalamic sites, our results showed an early microglial activation to be present also in forebrain regions outside of the middle cerebral artery (MCA) territory, such as the contralateral cortex and hippocampus. A unilateral microglial reaction was also detectable after long-term survival (>or = 4 weeks) in the pyramidal tracts, as well as in the corticospinal tracts at cervical but not lumbar spinal cord levels. Ischemia-induced neuronal damage, as evaluated by Nissl staining, was found only in cortical and thalamic regions. We conclude that the demonstration of reactive microglia indicates not only imminent ischemic neuronal damage within MCA territory but can also delineate extra-focal disturbances, possibly reflecting subtle and transitory changes in neuronal activity.}, Author = {Morioka, T. and Kalehua, A. N. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Neuroglia;Immunophenotyping;Rats;Inflammation;Lymphocytes;Rats, Wistar;Cerebral Infarction;11 Glia;Arterial Occlusive Diseases;Not relevant;Gliosis;Cerebral Arterial Diseases;Animals}, Medline = {93163419}, Month = {1}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Neurological Surgery, University of Florida, Gainesville 32610-0244.}, Pages = {123-32}, Pubmed = {8432904}, Title = {Characterization of microglial reaction after middle cerebral artery occlusion in rat brain}, Uuid = {1945975B-7C81-4086-85AB-A8E50F5BD568}, Volume = {327}, Year = {1993}} @article{Morioka:1992c, Abstract = {We have studied the cellular immune response that accompanies primary and metastatic brain cancers induced experimentally in rats by inoculation of RG-2 glioma and Walker 256 (W256) carcinoma cells, respectively. The inflammatory cell infiltrates were characterized with lectin histochemistry to visualize microglial cells and macrophages and with immunohistochemistry, using a panel of monoclonal antibodies, to detect major histocompatibility complex (MHC), lymphocytic, and macrophage antigens. The metastatic tumor was composed of a loose stroma with multiple, often large, necrotic areas, whereas the RG-2 glioma was composed of a dense collection of tumor cells showing only rare necrotic foci. Both tumor types were heavily infiltrated with microglia and/or macrophages, and these were positive for MHC Class II (Ia) antigens. Expression of MHC Class I antigens was absent from RG-2 glioma cells, but it was present in W256 metastatic carcinoma cells. The metastatic tumor was also characterized by a much heavier infiltrate of lymphocytes, as shown by the presence of cells positive for CD4, CD8, and leukocyte common antigens. These lymphocytic markers were absent from reactive microglia in the W256 carcinoma, whereas they were present in the RG-2 glioma. Polymorphonuclear leukocytes were seen only in the metastatic tumor. Our study delineates differences between the inflammatory cell infiltrates found in metastatic brain tumors and those found in primary brain tumors. The differences in cell composition and immunophenotype may indicate a more effective antitumor response in the metastatic tumor that could account for the observed tissue destruction.}, Author = {Morioka, T. and Baba, T. and Black, K. L. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0148-396X}, Journal = {Neurosurgery}, Keywords = {Neuroglia;Immunophenotyping;Glioma;Rats;Female;Not relevant;T-Lymphocytes;11 Glia;Neoplasm Transplantation;Macrophages;Brain Neoplasms;Carcinoma 256, Walker;Support, Non-U.S. Gov't;Animals;Phagocytosis}, Medline = {92310646}, Month = {6}, Nlm_Id = {7802914}, Number = {6}, Organization = {Department of Neurological Surgery, University of Florida, Gainesville.}, Pages = {891-6}, Pubmed = {1614593}, Title = {Inflammatory cell infiltrates vary in experimental primary and metastatic brain tumors}, Uuid = {7007F65B-3162-4048-9985-CF5A7992F5FA}, Volume = {30}, Year = {1992}} @article{Moroni:1978, Abstract = {Lipoprotein E. coli, a B-cell mitogen, is identified as a new agent inducing the release of endogenous C-type virus from mouse spleen cells. Like lipopolysaccharide, a previously identified inducer, this compound has a synergistic effect with 5-bromo-2'-deoxyuridine. Induced virus has the characteristic density as well as morphology of C-type viruses. Budding viruses are detected on cultured BALB/c cells by electron microscopy 2 to 4 days following culturing in the presence of lipoprotein. Pokeweed mitogen, a compound mitogenic for T- and B-cells was negative when tested for virus induction, both alone and in combination with 5-bromo-2'-deoxyuridine. Dextran sulphate, another B-cell mitogen, was negative for induction as well. However, when, combined with lipopolysaccharide, it enhanced the virus release induced by this mitogen. In contrast, no additive effects were observed either by combining dextran sulphate with other virus amplifying mitogens or by combinations of mitogens which both have virus-inducing ability. This finding is discussed with respect to B-cell differentiation.}, Author = {Moroni, C. and Schumann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0022-1317}, Journal = {J Gen Virol}, Keywords = {Mice, Inbred BALB C;Drug Synergism;Polysaccharides, Bacterial;Animals;Bacterial Proteins;Dextrans;Lipopolysaccharides;15 Retrovirus mechanism;Retroviridae;Mitogens;Cell Line;Escherichia coli;Mice;Virus Replication;Bromodeoxyuridine;24 Pubmed search results 2008;15 ERVs retroelements;Lectins;Lipoproteins}, Medline = {78131923}, Month = {3}, Nlm_Id = {0077340}, Number = {3}, Pages = {497-503}, Pubmed = {204733}, Title = {Mitogen induction of murine C-type viruses. IV. Effects of lipoprotein E. coli, pokeweed mitogen and dextran sulphate}, Uuid = {00F878C3-3CF0-485B-942C-F0AA89BF4DBB}, Volume = {38}, Year = {1978}} @article{Moroni:1975, Author = {Moroni, C. and Schumann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {15 ERVs retroelements;Lipopolysaccharides;Animals;Mice, Inbred BALB C;RNA-Directed DNA Polymerase;Virus Replication;Lectins;Retroviridae;Mitogens;Concanavalin A;15 Retrovirus mechanism;Polynucleotides;Spleen;Mice;24 Pubmed search results 2008;Templates, Genetic;Cells, Cultured}, Medline = {75100417}, Month = {3}, Nlm_Id = {0410462}, Number = {5495}, Pages = {60-1}, Pubmed = {46591}, Title = {Lipopolysaccharide induces C-type virus in short term cultures of BALB/c spleen cells}, Uuid = {AD3D0EED-B499-43AE-9E0E-2AE095DADB50}, Volume = {254}, Year = {1975}} @article{Moroni:1977, Author = {Moroni, C. and Schumann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {15 ERVs retroelements;Genes, Viral;Retroviridae;Immunosuppression;15 Retrovirus mechanism;Antibody Formation;Cells, Cultured;Spleen;Antigen-Antibody Reactions;Antibodies, Viral;24 Pubmed search results 2008}, Medline = {78031209}, Month = {10}, Nlm_Id = {0410462}, Number = {5629}, Pages = {600-1}, Pubmed = {199846}, Title = {Are endogenous C-type viruses involved in the immune system?}, Uuid = {3C2F634B-E422-4714-BB95-F9419BF28D4D}, Volume = {269}, Year = {1977}} @article{Moroni:1975a, Abstract = {In short-term cultures of BALB/c spleen cells, treatment with a combination of 5-bromo-2'-deoxyuridine (BrdU) and either lipopolysaccharide W. Escherichia coli or concanavalin A resulted in release of C-type virus into the medium. Only lipopolysaccharide induced virus release when given alone. This could be potentiated by a combined treatment with BrdU. In contrast, phytohemagglutinin at mitogenic concentration had no effect with or without BrdU, suggesting that inducibility may vary between various mitogen-responsive spleen cell populations. In AKR mice, spontaneous virus release was detectable in nonstimulated spleen cell cultures. This could be potentiated by lipopolysaccharide, whereas no further increase occurred upon additional BrdU treatment. The induced viruses had C-type characteristics in that they contained reverse transcriptase that could be distinguished from cellular enzymes by template-primer preference experiments. Furthermore, the enzyme activities were particle-associated, banding in isopycnic sucrose gradients at 1.15-1.17 g/cm-3. The presence of C-type viruses was confirmed by electron microscopy.}, Author = {Moroni, C. and Schumann, G. and Robert-Guroff, M. and Suter, E. R. and Martin, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Mice, Inbred BALB C;Polysaccharides, Bacterial;Animals;Gammaretrovirus;Cells, Cultured;DNA;Lipopolysaccharides;Thymidine;15 Retrovirus mechanism;RNA-Directed DNA Polymerase;Retroviridae;Mitogens;Concanavalin A;Mice;Virus Replication;Bromodeoxyuridine;24 Pubmed search results 2008;15 ERVs retroelements;Spleen;Lectins}, Medline = {75139495}, Month = {2}, Nlm_Id = {7505876}, Number = {2}, Pages = {535-8}, Pubmed = {47632}, Title = {Induction of endogenous murine C-type virus in spleen cell cultures treated with mitogens and 5-bromo-2'-deoxyuridine}, Uuid = {1BA03DBE-BDB8-11DA-969D-000D9346EC2A}, Volume = {72}, Year = {1975}} @article{Moroni:1980, Abstract = {Goat and rat antisera directed against Friend leukemia virus (anti-FLV) were found to be B-lymphocyte mitogens stimulating DNA synthesis in these cells but not in T lymphocytes. Membrane fluorescence microscopy showed that anti-FLV reacts with a subset of B lymphocytes of which the majority express immunoglobulin mu chains. The mitogenic effect was found with all mouse strains tested including 129 and AKR. Absorption experiments with purified viruses indicated that the mitogenic effect is specific for an antigen present in murine leukemia viruses of the FMR subgroup. In absorption experiments with viable cells, the antigen involved in mitogenicity was found to be expressed on Friend erythroleukemia cell lines (4/4) and on myelomas (2/2) but not on normal thymus T lymphomas (0/2) or on rabbit or mink cells infected with BALB/c xenotropic virus. Preincubation of spleen cells with anti-gp70 antiserum inhibited the mitogenic effect of anti-FLV but not of lipopolysaccharide.}, Author = {Moroni, C. and Forni, L. and Hunsmann, G. and Schumann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {15 ERVs retroelements;Lymphocyte Activation;Antibodies, Viral;B-Lymphocytes;DNA;Mitogens;Antigens, Surface;Friend murine leukemia virus;Thymus Gland;Helper Viruses;15 Retrovirus mechanism;Mice;Spleen;24 Pubmed search results 2008;Animals;Antigen-Antibody Reactions}, Medline = {80190078}, Month = {3}, Nlm_Id = {7505876}, Number = {3}, Pages = {1486-90}, Pubmed = {6966399}, Title = {Antibody directed against Friend leukemia virus stimulates DNA synthesis in a subpopulation of mouse B lymphocytes}, Uuid = {5F86876A-7DCD-4D77-9B06-FA22C3D5CA3C}, Volume = {77}, Year = {1980}} @article{Moroni:1976, Author = {Moroni, C. and Schumann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {Lysogeny;Polysaccharides, Bacterial;Tuberculin;Animals;Comparative Study;DNA;Lipopolysaccharides;15 Retrovirus mechanism;RNA-Directed DNA Polymerase;B-Lymphocytes;Cross Reactions;Mitogens;Retroviridae;Rauscher Virus;Cell Line;Escherichia coli;Salmonella;Mice;24 Pubmed search results 2008;Virus Replication;Bromodeoxyuridine;15 ERVs retroelements}, Medline = {76272705}, Month = {8}, Nlm_Id = {0110674}, Number = {1}, Pages = {17-22}, Pubmed = {60824}, Title = {Mitogen induction of murine C-type viruses. II. Effect of B-lymphocyte mitogens}, Uuid = {F5D84104-8ADE-4D33-A6BA-4C74BB2DC16D}, Volume = {73}, Year = {1976}} @article{Moroz:1992, Abstract = {Rapid ballistic food-getting movement characteristics were studied in albino rats. After ablation of the second area of the frontal cortex contralaterally as to the preferred extremity the number of attempts increased and their duration with reorganization of the phase structure of movements decreased. The habit of food extraction was lost after bilateral ablation of the cortex. The obtained results have illustrated significance of the frontal cortex in formation and realization of moving programmes.}, Author = {Moroz, V. M. and Bratus', N. V. and Vlasenko, O. V. and Ioltukhovski, M. V. and Kozlovskaia, L. P. and Makota, A. S. and Udod, O. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0028-2561}, Journal = {Neirofiziologiia}, Keywords = {Movement;Rats;English Abstract;Habits;Animals;Male;24 Pubmed search results 2008;Feeding Behavior;Frontal Lobe}, Medline = {92284943}, Nlm_Id = {0231364}, Number = {2}, Pages = {186-92}, Pubmed = {1598123}, Title = {[Role of the frontal cortex in the organization of rapid ballistic movements of rats]}, Uuid = {0E86295F-4A85-4059-9AFE-561019EC55DE}, Volume = {24}, Year = {1992}} @article{Morozov:2002, Abstract = {Several techniques enable to inject intracellularly neurons with dyes and to use light and electron microscopy to correlate the physiological data with the morphological properties of the neuron. However, the ultrastructure of the neuron is usually obscured by the injected dye thus notably precluding the analysis of the postsynaptic specialisation and that of the other organelles. To overcome this problem, we have developed a technique based on fluorophore- and ultra small gold-conjugated streptavidins. We report, that this method facilitates the identification of intracellular organelles of the biocytin-filled neuron and of postsynaptic densities. This method is valid for the study of early postnatal neurons that are particularly refractory to this type of analysis. The procedure introduced here consists of the following steps: (1) injection of biocytin into the neuron by a patch-clamp pipette, (2) aldehyde fixation, (3) reaction with a fluorophore-conjugated streptavidin, (4) analysis with a fluorescence microscope, (5) formation of avidin-biotin complexes (ABC), (6) reaction with an ultra small gold-conjugated streptavidin, (7) silver enhancement of gold, (8) postfixation with osmium tetroxide and embedding in resin, (9) ultrathin sectioning and analysis with an electron microscope. Using this method, we show that in early postnatal hippocampal neurons, that have been injected with biocytine, it is possible to determine the morphology of the dendritic and axonal trees (including very thin details such as spines and filopodia) and to identify the localisation of the symmetric and asymmetric synapses on dendrites of the injected neuron.}, Author = {Morozov, Youri and Khalilov, Ilgam and Ben-Ari, Yehezkel and Represa, Alfonso}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Fluorescent Dyes;Synaptic Membranes;Lysine;Organelles;Animals;Rats;21 Epilepsy;Neuroanatomy;Axons;Hippocampus;Pyramidal Cells;Organ Culture Techniques;Microscopy, Fluorescence;Tissue Embedding;Dendrites;Animals, Newborn;Neurons;21 Neurophysiology;Streptavidin;Interneurons;24 Pubmed search results 2008;Microscopy, Electron;Immunohistochemistry;Tissue Fixation;Fixatives}, Medline = {22079920}, Month = {5}, Nlm_Id = {7905558}, Number = {1}, Organization = {INMED/INSERM U29, 163 Route de Luminy, BP 13, 13009 Marseille, France.}, Pages = {81-5}, Pii = {S0165027002000766}, Pubmed = {12084567}, Title = {Correlative fluorescence and electron microscopy of biocytin-filled neurons with a preservation of the postsynaptic ultrastructure}, Uuid = {B443D284-8446-451B-BF37-081407F038A1}, Volume = {117}, Year = {2002}} @article{Morris:2001, Abstract = {Though the cytomechanics of spectrin have been explored only for erythrocytes, it is thought that the spectrin skeleton acts universally to support the otherwise mechanically vulnerable cell surface bilayer. Evidence for this role is beginning to accumulate and is reviewed here. Compared to that for erythrocytes, cells whose simplicity facilitates biophysical approaches, the evidence is indirect. One way that membrane skeleton/bilayer interactions have been probed is via the behavior of mechanosusceptible ion channels - channel whose gating is perturbed by abnormally high bilayer tension. These initially unresponsive channels become progressively more mechanoresponsive as stretch and chemical reagents damage the membrane skeleton. The straightforward implication is that the intact membrane skeleton is mechanoprotective. In non-erythroid cells there is continual trafficking of bilayer to and from the plasma membrane. Some of the traffic involves spectrin-lined vacuolar membrane. Several lines of evidence suggest that when neurons elongate and remodel their neurites, membrane skeleton-based mechanoprotection allows the dynamic vacuoles and the plasma membrane to participate in mechanosensitive surface area expansion and retrieval.}, Author = {Morris, C. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {1425-8153}, Journal = {Cell Mol Biol Lett}, Keywords = {Cell Membrane;Neurites;Cytoskeleton;Ion Channels;Human;Spectrin;Not relevant;Growth Cones;11 Glia;Vacuoles;review, tutorial;Electrophysiology;Stress, Mechanical;Animals;Biological Transport;review;Neurons}, Medline = {21481651}, Nlm_Id = {9607427}, Number = {3}, Organization = {Neurosciences, Ottawa Health Research Institute, Ottawa Hospital, 725 Parkdale Ave, Ottawa, Ontario, Canada K1Y 4K9.}, Pages = {703-20}, Pubmed = {11598643}, Title = {Mechanoprotection of the plasma membrane in neurons and other non-erythroid cells by the spectrin-based membrane skeleton}, Uuid = {F7B4ADBD-D818-4496-8067-4912B19A659F}, Volume = {6}, Year = {2001}} @article{Morrison:2000, Abstract = {The genesis of vertebrate peripheral ganglia poses the problem of how multipotent neural crest stem cells (NCSCs) can sequentially generate neurons and then glia in a local environment containing strong instructive neurogenic factors, such as BMP2. Here we show that Notch ligands, which are normally expressed on differentiating neuroblasts, can inhibit neurogenesis in NCSCs in a manner that is completely dominant to BMP2. Contrary to expectation, Notch activation did not maintain these stem cells in an uncommitted state or promote their self-renewal. Rather, even a transient activation of Notch was sufficient to cause a rapid and irreversible loss of neurogenic capacity accompanied by accelerated glial differentiation. These data suggest that Notch ligands expressed by neuroblasts may act positively to instruct a cell-heritable switch to gliogenesis in neighboring stem cells. 0092-8674 Journal Article}, Author = {Morrison, S. J. and Perez, S. E. and Qiao, Z. and Verdi, J. M. and Hicks, C. and Weinmaster, G. and Anderson, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Cell}, Keywords = {Neuregulin-1/metabolism;Cell Differentiation;Human;Signal Transduction;Receptors, Cell Surface/*metabolism;Animals;Neurons/*cytology;Fibroblasts/cytology;Solubility;Cell Line, Transformed;10 Development;Immunoglobulins, Fc/metabolism;Membrane Proteins/*metabolism;Stem Cells/*cytology;Neural Crest/*cytology;Support, Non-U.S. Gov't;Chick Embryo;Support, U.S. Gov't, P.H.S.;Bone Morphogenetic Proteins/metabolism;Mice;Neuroglia/*cytology;F;Recombinant Fusion Proteins/genetics/metabolism}, Number = {5}, Organization = {Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.}, Pages = {499-510}, Pubmed = {10850492}, Title = {Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells}, Uuid = {305DEE6E-2151-4CE4-B1E4-90F6DE769EDE}, Volume = {101}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10850492}} @article{Morrison:2001, Abstract = {Recent results suggest that stem cells from one tissue can give rise to cells from developmentally unrelated tissues. These results strongly support the idea that certain progenitors retain much broader developmental potentials than expected, and other progenitors may be able to acquire broader potentials in culture.}, Author = {Morrison, S. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Stem Cells;review, tutorial;Cell Lineage;review}, Medline = {21109566}, Month = {1}, Nlm_Id = {9107782}, Number = {1}, Organization = {Howard Hughes Medical Institute, Department of Internal Medicine, 3215 CCGC, University of Michigan, Ann Arbor, Michigan 48109-0934, USA.}, Pages = {R7-9}, Pii = {S0960982200000336}, Pubmed = {11166187}, Title = {Stem cell potential: can anything make anything?}, Uuid = {BAA1C70C-C26D-11DA-969D-000D9346EC2A}, Volume = {11}, Year = {2001}, url = {papers/Morrison_CurrBiol2001.pdf}} @article{Morrison:2000a, Author = {Morrison, S. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:54 -0400}, Journal = {Neuron}, Keywords = {10 Development;Neurons/cytology;Fibroblast Growth Factor/pharmacology;Cell Lineage/*physiology;F both;Central Nervous System/*cytology/*embryology;Stem Cells/*cytology/drug effects;Cell Differentiation/drug effects/*physiology;Neuroglia/cytology;Epidermal Growth Factor/pharmacology}, Number = {1}, Organization = {Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan, Ann Arbor 48109, USA.}, Pages = {1-3.}, Title = {The last shall not be first: the ordered generation of progeny from stem cells}, Uuid = {DB335A62-39D3-4A6A-9B5F-A97CA3E9E797}, Volume = {28}, Year = {2000}, url = {papers/Morrison_Neuron2000.pdf}} @article{Morshead:1998, Abstract = {The adult mammalian forebrain contains a population of multipotential neural stem cells in the subependyma of the lateral ventricles whose progeny are the constitutively proliferating cells, which divide actively throughout life. The adult mammalian brain is ideal for examining the kinetics of the stem cells due to their strict spatial localization and the limited and discrete type of progeny generated (constitutively proliferating cells). Clonal lineage analyses 6 days after retrovirus infection revealed that under baseline conditions 60\%of the constitutively proliferating cells undergo cell death, 25\%migrate to the olfactory bulb and 15\%remain confined to the lateral ventricle subependyma (where they reside for approximately 15 days). Analysis of single cell clones 31 days after retroviral infection revealed that the stem cell divides asymmetrically to self-renew and give rise to constitutively proliferating cells. Following repopulation of the depleted subependyma the average clone size is 2.8 times larger than control, yet the absolute number of cells migrating to the olfactory bulb is maintained and the stem cell retains its asymmetric mode of division. The number of neural stem cells in the adult forebrain 33 days after repopulation of the subependyma was estimated using bromodeoxyuridine labeling of subepenydmal cells. There were calculated to be 1200-1300 cells between the rostral corpus callosum and rostral anterior commissure; these data support a lineage model similar to those based on stem cell behavior in other tissue types.}, Author = {Morshead, C. M. and Craig, C. G. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Development}, Keywords = {Prosencephalon/*cytology;Ependyma/cytology;BB;Animal;Cell Count;02 Adult neurogenesis migration;Retroviridae/physiology;Kinetics;Cell Movement;Male;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;Cell Lineage;Olfactory Bulb/cytology;Stem Cells/*cytology/virology;Mice;Cell Division;Clone Cells;Cell Death}, Number = {12}, Organization = {Neurobiology Research Group, Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. cinci.morshead\@utoronto.ca}, Pages = {2251-61.}, Title = {In vivo clonal analyses reveal the properties of endogenous neural stem cell proliferation in the adult mammalian forebrain}, Uuid = {6563A2A8-31D6-4AE3-94F8-2B176785FB68}, Volume = {125}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9584124%20http://www.biologists.com/Development/125/12/dev1261.html}} @article{Moscona:1992, Abstract = {Cells can be persistently infected with human parainfluenza virus type 3 (HPF3) by using a high multiplicity of infection (MOI) (>or = 5 PFU per cell). The persistently infected cells exhibit no cytopathic effects and do not fuse with each other, yet they readily fuse with uninfected cells. We have previously shown that the failure of the persistently infected cells to fuse with each other is due to the lack of a receptor on these cells for the viral hemagglutinin-neuraminidase glycoprotein, and we have established that both fusion and hemagglutinin-neuraminidase proteins are needed for cell fusion mediated by HPF3. We then postulated that the generation of persistent infection and the failure of cells infected with HPF3 at high MOI to form syncytia are both due to the action of viral neuraminidase in the high-MOI inoculum. In this report, we describe experiments to test this hypothesis and further investigate the receptor requirements for HPF3 infection and cell fusion. A normally cytopathic low-MOI HPF3 infection can be converted into a noncytopathic infection by the addition of exogenous neuraminidase, either in the form of a purified enzyme or as UV-inactivated HPF3 virions. Evidence is presented that the receptor requirements for an HPF3 virus particle to infect a cell are different from those for fusion between cells. By treating infected cells in culture with various doses of neuraminidase, we demonstrate that virus spreads from cell to cell in the complete absence of cell-cell fusion. We compare the outcome of HPF3 infection in the presence of excess neuraminidase with that of another paramyxovirus (simian virus 5) and provide evidence that these two viruses differ in their receptor requirements for mediating fusion.}, Author = {Moscona, A. and Peluso, R. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Neuraminidase;Viral Fusion Proteins;Human;Cells, Cultured;N-Acetylneuraminic Acid;Retroviruses, Simian;Models, Biological;15 Retrovirus mechanism;Cell Fusion;11 Glia;08 Aberrant cell cycle;Support, Non-U.S. Gov't;Sialic Acids;Hemagglutinins, Viral;Membrane Fusion;Support, U.S. Gov't, P.H.S.;Receptors, Virus;Virus Replication;Parainfluenza Virus 3, Human}, Medline = {93021352}, Month = {11}, Nlm_Id = {0113724}, Number = {11}, Organization = {Department of Pediatrics and Cell Biology, Mount Sinai School of Medicine, New York, New York 10029-6574.}, Pages = {6280-7}, Pubmed = {1328668}, Title = {Fusion properties of cells infected with human parainfluenza virus type 3: receptor requirements for viral spread and virus-mediated membrane fusion}, Uuid = {1F24ABE8-37B8-42B6-BAD0-B81906397345}, Volume = {66}, Year = {1992}, url = {papers/Moscona_JVirol1992.pdf}} @article{Moss:2004, Abstract = {Deep brain stimulation (DBS) is used to treat a variety of severe medically intractable movement disorders, including Parkinson's disease, tremor and dystonia. There have been few studies examining the effect of chronic DBS on the brains of Parkinson's disease patients. Most of these post mortem studies concluded that chronic DBS caused mild gliosis around the lead track and did not damage brain tissue. There have been no similar histopathological studies on brains from dystonic patients who have undergone DBS. In this study, our objective was to discover whether tissue would be attached to DBS electrodes removed from patients for routine clinical reasons. We hoped that by examining explanted DBS electrodes using scanning (SEM) and/or transmission (TEM) electron microscopy we might visualize any attached tissue and thus understand the electrode-human brain tissue interaction more accurately. Initially, SEM was performed on one control DBS electrode that had not been implanted. Then 21 (one subthalamic nucleus and 20 globus pallidus internus) explanted DBS electrodes were prepared, after fixation in 3\%glutaraldehyde, for SEM (n = 9) or TEM (n = 10), or both (n = 2), according to departmental protocol. The electrodes were sourced from two patients with Parkinson's disease, one with myoclonic dystonia, two with cervical dystonia and five with primary generalized dystonia, and had been in situ for 11 and 31 months (Parkinson's disease), 16 months (myoclonic dystonia), 14 and 24 months (cervical dystonia) and 3-24 months (primary generalized dystonia). Our results showed that a foreign body multinucleate giant cell-type reaction was present in all TEM samples and in SEM samples, prewashed to remove surface blood and fibrin, regardless of the diagnosis. Some of the giant cells were >100 microm in diameter and might have originated from either fusion of parenchymal microglia, resident perivascular macrophage precursors and/or monocytes/macrophages invading from the blood stream. The presence of mononuclear macrophages containing lysosomes and sometimes having conspicuous filopodia was detected by TEM. Both types of cell contained highly electron-dense inclusions, which probably represent phagocytosed material. Similar material, the exact nature of which is unknown, was also seen in the vicinity of these cells. This reaction was present irrespective of the duration of implantation and may be a response to the polyurethane component of the electrodes' surface coat. These findings may be relevant to our understanding of the time course of the clinical response to DBS in Parkinson's disease and various forms of dystonia, as well as contributing to the design characteristics of future DBS electrodes.}, Author = {Moss, J. and Ryder, T. and Aziz, T. Z. and Graeber, M. B. and Bain, P. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1460-2156}, Journal = {Brain}, Keywords = {Microscopy, Electron, Scanning;Dystonia;Humans;Device Removal;Middle Aged;Granuloma, Giant Cell;Female;Giant Cells, Foreign-Body;Parkinson Disease;Granuloma, Foreign-Body;11 Glia;Time Factors;Male;Deep Brain Stimulation;Globus Pallidus;Adult;Surface Properties;Microscopy, Electron;Electrodes, Implanted;Research Support, Non-U.S. Gov't}, Month = {12}, Nlm_Id = {0372537}, Number = {Pt 12}, Organization = {Electron Microscopy Unit, Department of Histopathology, Charing Cross Hospital, Hammersmith Hospitals NHS Trust, London, UK.}, Pages = {2755-63}, Pii = {awh292}, Pubmed = {15329356}, Title = {Electron microscopy of tissue adherent to explanted electrodes in dystonia and Parkinson's disease}, Uuid = {31A944FA-6274-4D1C-B75D-4CB6DBD7979C}, Volume = {127}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/brain/awh292}} @article{Mott:2004, Abstract = {Although considered an immunologically privileged site, the central nervous system (CNS) can display significant inflammatory responses, which may play a pathogenic role in a number of neurological diseases. Microglia appear to be particularly important for initiating and sustaining CNS inflammation. These cells exist in a quiescent form in the normal CNS, but acquire macrophage-like properties (including active phagocytosis, upregulation of proteins necessary for antigen presentation, and production of proinflammatory cytokines) after stimulation with inflammatory substances such as lipopolysaccharide (LPS). Recent studies have focused on elucidating the role of neurons in the regulation of microglial inflammatory responses. In the present study, we demonstrate, using neuron-microglial cocultures, that neurons are capable of inhibiting LPS-induced tumor necrosis factor-alpha (TNF-alpha) production by microglia. This inhibition appears to be dependent on secretion of substances at axon terminals, as treatment with the presynaptic calcium channel blocker omega-conotoxin abolishes this inhibitory effect. Moreover, we show that conditioned medium from neuronal cultures similarly inhibits microglial TNF-alpha production, which provides additional evidence that neurons secrete inhibitory substances. We previously demonstrated that the transmembrane protein-tyrosine phosphatase CD45 plays an important role in negatively regulating microglial activation. The recent characterization of CD22 as an endogenous ligand of this receptor led us to investigate whether neurons express this protein. Indeed, we were able to demonstrate CD22 mRNA and protein expression in cultured neurons and mouse brain, using reverse transcriptase-polymerase chain reaction and antibody-based techniques. Furthermore, we show that neurons secrete CD22, which functions as an inhibitor of microglial proinflammatory cytokine production.}, Author = {Mott, Ryan T. and Ait-Ghezala, Ghania and Town, Terrence and Mori, Takashi and Vendrame, Martina and Zeng, Jin and Ehrhart, Jared and Mullan, Michae and Tan, Jun}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Antigens, CD45;Tumor Necrosis Factor;Presynaptic Terminals;Antigens, Differentiation, B-Lymphocyte;Feedback, Biochemical;Animals;Cells, Cultured;Calcium Channel Blockers;Dose-Response Relationship, Drug;Brain;Microglia;Lipopolysaccharides;Cell Communication;Antigens, CD;Culture Media, Conditioned;RNA, Messenger;Not relevant;11 Glia;Support, Non-U.S. Gov't;Coculture;Neurons;Support, U.S. Gov't, P.H.S.;Mice;Lectins;Ligands;Cytokines}, Month = {5}, Nlm_Id = {8806785}, Number = {4}, Organization = {Department of Pathology, Duke University Medical Center, Durham, North Carolina, USA.}, Pages = {369-79}, Pubmed = {15095367}, Title = {Neuronal expression of CD22: novel mechanism for inhibiting microglial proinflammatory cytokine production}, Uuid = {19AACB03-0982-4A67-8FCB-201D55B80A63}, Volume = {46}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20009}} @article{Mount:2007, Abstract = {Growing evidence implicates microglia in the loss of dopaminergic neurons in Parkinson's disease (PD). However, factors mediating microglial activation in PD are poorly understood. Proinflammatory cytokines, such as interferon-gamma (IFN-gamma), orchestrate the actions of microglia. We report here that PD patients express significantly elevated levels of IFN-gamma in their blood plasma. After this initial finding, we found that IFN-gamma-deficient mice displayed attenuated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced substantia nigra pars compacta dopaminergic cell loss along with reduced loss of striatal tyrosine hydroxylase and dopamine transporter fiber density. MPTP-induced depletion of striatal dopamine and its metabolite DOPAC (3,4-dihydroxyphenylacetic acid), as well as deltaFosB, a marker of postsynaptic dysfunction, were also attenuated in these knock-out mice. Consistent with the role for IFN-gamma in microglial activation, MPTP-induced morphological activation of microglia was abrogated compared with wild-type mice. To examine more mechanistically the role of IFN-gamma in microglial activation, we evaluated the interactions between microglia and dopaminergic neurons in an in vitro mixed microglia/midbrain neuron rotenone-induced death paradigm. In this in vitro paradigm, dopaminergic neurons are selectively damaged by rotenone. Exogenous IFN-gamma ligand alone and without rotenone resulted in dopaminergic cell loss, but only in the presence of microglia. The addition of an IFN-gamma neutralizing antibody attenuated neuronal loss as a result of rotenone treatment. The presence of only wild-type microglia and not those deficient in IFN-gamma receptor elicited significant dopaminergic cell loss when exposed to rotenone. Neurons deficient in IFN-gamma receptor, however, did not display increased resistance to death. Finally, levels of IFN-gamma message increased in microglia in response to rotenone. Together, these data suggest that IFN-gamma participates in death of dopaminergic neurons by regulating microglial activity.}, Author = {Mount, Matthew P. and Lira, Arman and Grimes, David and Smith, Patrice D. and Faucher, Sylvie and Slack, Ruth and Anisman, Hymie and Hayley, Shawn and Park, David S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Dopamine;Animals;Cells, Cultured;Coculture Techniques;Middle Aged;comparative study;Humans;Interferon Type II;Microglia;Cell Count;21 Neurodegenerative;Parkinson Disease;Mice, Inbred C57BL;11 Glia;research support, non-u.s. gov't;Male;Aged;Mice, Knockout;21 Neurophysiology;Neurons;Adult;Mice;24 Pubmed search results 2008;Cell Death;research support, u.s. gov't, non-p.h.s.}, Month = {3}, Nlm_Id = {8102140}, Number = {12}, Organization = {Ottawa Health Research Institute, Neuroscience Group, Ottawa, Ontario, Canada K1H 8M5.}, Pages = {3328-37}, Pii = {27/12/3328}, Pubmed = {17376993}, Title = {Involvement of interferon-gamma in microglial-mediated loss of dopaminergic neurons}, Uuid = {8C2B1810-AC1C-4A65-AD0E-ACDD6FCB0C87}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5321-06.2007}} @article{Mouritzen-Dam:1992, Author = {Mouritzen-Dam, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0922-9833}, Journal = {Epilepsy Res Suppl}, Keywords = {Epilepsy;Brain;Cell Differentiation;Cerebral Cortex;24 Pubmed search results 2008;21 Neurophysiology;21 Epilepsy;Choristoma;Brain Neoplasms;Animals;Cell Movement;Humans;review;Neurons}, Medline = {93159655}, Nlm_Id = {8913231}, Organization = {Neurological Research Laboratory, Hvid\ovre University Hospital, Copenhagen, Denmark.}, Pages = {61-5}, Pubmed = {1285915}, Title = {The possible pathological importance of dysgenesis, heterotopia and other cellular displacements in the brain}, Uuid = {D22A8110-B02B-4729-A2DF-6963BC8D2CD6}, Volume = {9}, Year = {1992}} @article{Mourzina:2006, Abstract = {A spatially resolved delivery of substances integrated with cell culture substrates shows promise for application in pharmacological assays, bioanalytical studies on cell signaling pathways and cell-based biosensors, where control over the extracellular biochemical environment with a cellular resolution is desirable. In this work, we studied a biohybrid system where rat embryonic cortical neuronal networks are reconstructed on microstructured silicon chips and interfaced to microfluidics. The design of cell-cell and cell-medium interactions in confined geometries is presented. We developed an aligned microcontact printing technique (AmicroCP) for poly(lysine)-extracellular matrix proteins on microstructured chips, which allows a high degree of geometrical control over the network architecture and alignment of the neuronal network with the microfluidic features of a substrate. Spatially resolved on-chip delivery of compounds with a cellular resolution is demonstrated by chemical stimulation of patterned rat cortical neurons within a network with a number of solutions of excitatory neurotransmitter glutamate delivered via microfluidics. The combination of the system described with a patch-clamp technique allowed both modulation of the biochemical environment on a cellular level and the monitoring of electrophysiological properties in the reconstructed rat embryonic cortical networks changed by this microenvironment.}, Author = {Mourzina, Yulia and Kaliaguine, Dmitry and Schulte, Petra and Offenh{\"a}usser, Andreas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1873-4324}, Journal = {Anal Chim Acta}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0370534}, Number = {2}, Organization = {Institute of Bio- and Nanosystems and Center of Nanoelectronic Systems for Information Technology, Research Center J{\"u}lich, 52425 J{\"u}lich, Germany. y.mourzina\@fz-juelich.de}, Pages = {281-9}, Pii = {S0003-2670(06)01225-6}, Pubmed = {17723603}, Title = {Patterning chemical stimulation of reconstructed neuronal networks}, Uuid = {3E81D06E-3ACD-43F0-ABC6-477BF0661217}, Volume = {575}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.aca.2006.06.010}} @article{Mozdziak:2000, Abstract = {5-Bromo-2'-deoxyuridne (BrdU) and 3H-thymidine label mitotically active cells, but they do not adequately mark the progeny of dividing cells for long term study. An alternative method is to label cells using the replication-defective CXL retroviral vector, which carries the lacZ gene encoding beta-galactosidase; however, the ability of the CXL retroviral vector to pulse-label mitotically active cells selectively is not known. Cultures of proliferating muscle cells were simultaneously incubated with the CXL retrovirus and BrdU (10 microM) for 2 hr. After removing the retrovirus containing medium, the cells were maintained for an additional 24 hr in vitro before they were stained to detect beta-galactosidase and BrdU simultaneously. More than 95\%of beta-galactosidase positive cells were also BrdU positive suggesting that the majority of beta-galactosidase positive cells were in the S-phase of the cell cycle at the time of CXL retroviral administration. Therefore, the CXL retroviral vector is an appropriate pulse marker for dividing cells, and it is useful when it is desirable to know the fate of the progeny of a particular cell following a mitotic event.}, Author = {Mozdziak, P. and Schultz, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {1052-0295}, Journal = {Biotech Histochem}, Keywords = {beta-Galactosidase;Animals;Cells, Cultured;Injections, Intramuscular;DNA;Research Support, U.S. Gov't, Non-P.H.S.;Sensitivity and Specificity;15 Retrovirus mechanism;Turkeys;Staining and Labeling;Retroviridae;Get paper from library;Genetic Vectors;Defective Viruses;evaluation studies;Muscle, Skeletal;Lac Operon;Cell Division;24 Pubmed search results 2008;Biological Markers;Bromodeoxyuridine}, Medline = {20405109}, Month = {5}, Nlm_Id = {9107378}, Number = {3}, Organization = {Department of Poultry Science, North Carolina State University, Raleigh, North Carolina 27695, USA. pemozdzi\@unity.ncsu.edu}, Pages = {141-6}, Pubmed = {10950176}, Title = {Retroviral labeling is an appropriate marker for dividing cells}, Uuid = {862545B3-05CC-4950-8017-AA46684F4C09}, Volume = {75}, Year = {2000}} @article{Moller:1996, Abstract = {Thrombospondin (TSP) is a multifunctional extracellular matrix protein that plays a role in neuronal migration and axonal outgrowth in the developing central nervous system. In the current study we have examined the localization and regulation of TSP immunoreactivity (TSP-IR) during neuronal regeneration in the axotomized facial motor nucleus using Western blotting and light and electron microscopy. Transection of the facial nerve led to a gradual increase in TSP-IR in the regenerating motoneurons, peaking 4-7 days after injury (DAI). In addition to regenerating neurons, axotomy also caused a rapid upregulation of TSP-IR on activated microglia throughout the facial nucleus, with a maximum of 2-3 DAI, and a second increase at 14-21 DAI on microglial aggregates surrounding degenerating motoneurons and in neuronophagic microglia. In summary, injury leads to the induction of thrombospondin on axotomized neurons and activated microglia, peaking at the times of maximal posttraumatic microglial proliferation and during neuronal phagocytosis. Since thrombospondin is a multimodal extracellular matrix protein with a variety of cell attachment sites, thrombospondin might serve to link microglia and injured neurons, followed by microglial proliferation and removal of the neuronal debris.}, Author = {M{\"o}ller, J. C. and Klein, M. A. and Haas, S. and Jones, L. L. and Kreutzberg, G. W. and Raivich, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Membrane Glycoproteins;Thrombospondins;Motor Neurons;Facial Nerve;Immunohistochemistry;Microscopy, Electron;Regeneration;Time Factors;Not relevant;11 Glia;Mice;Animals;Mice, Inbred Strains}, Medline = {96372786}, Month = {6}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Neuromorphology, Max-Planck Institute for Psychiatry, Martinsried, Germany.}, Pages = {121-32}, Pii = {10.1002/(SICI)1098-1136(199606)17:2<121::AID-GLIA4>3.0.CO;2-5}, Pubmed = {8776579}, Title = {Regulation of thrombospondin in the regenerating mouse facial motor nucleus}, Uuid = {4EE7A346-AC66-455B-978A-A5088032D1CC}, Volume = {17}, Year = {1996}} @article{Mrsic-Flogel:2007, Abstract = {Experience-dependent plasticity is crucial for the precise formation of neuronal connections during development. It is generally thought to depend on Hebbian forms of synaptic plasticity. In addition, neurons possess other, homeostatic means of compensating for changes in sensory input, but their role in cortical plasticity is unclear. We used two-photon calcium imaging to investigate whether homeostatic response regulation contributes to changes of eye-specific responsiveness after monocular deprivation (MD) in mouse visual cortex. Short MD durations decreased deprived-eye responses in neurons with binocular input. Longer MD periods strengthened open-eye responses, and surprisingly, also increased deprived-eye responses in neurons devoid of open-eye input. These bidirectional response adjustments effectively preserved the net visual drive for each neuron. Our finding that deprived-eye responses were either weaker or stronger after MD, depending on the amount of open-eye input a cell received, argues for both Hebbian and homeostatic mechanisms regulating neuronal responsiveness during experience-dependent plasticity.}, Author = {Mrsic-Flogel, Thomas D. and Hofer, Sonja B. and Ohki, Kenichi and Reid, R. Clay and Bonhoeffer, Tobias and H{\"u}bener, Mark}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Animals;Photic Stimulation;Neuronal Plasticity;Visual Pathways;Sensory Deprivation;Vision, Monocular;Mice, Inbred C57BL;Calcium;research support, non-u.s. gov't;Time Factors;Eyelids;Vision, Binocular;Eye;Animals, Newborn;Action Potentials;Neurons;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Dominance, Ocular;Visual Cortex;Brain Mapping}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Cellular and Systems Neurobiology, Max Planck Institute of Neurobiology, D-82152 Martinsried, Germany. flogel\@neuro.mpg.de}, Pages = {961-72}, Pii = {S0896-6273(07)00408-4}, Pubmed = {17582335}, Title = {Homeostatic regulation of eye-specific responses in visual cortex during ocular dominance plasticity}, Uuid = {A14FFF68-53AD-41AB-B166-DFFED20241F9}, Volume = {54}, Year = {2007}, url = {papers/Mrsic-Flogel_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.05.028}} @article{Mrzljak:1990, Author = {Mrzljak, L. and Uylings, H. B. and Van Eden, C. G. and Jud{\'a}s, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0079-6123}, Journal = {Prog Brain Res}, Keywords = {Neurons;Frontal Lobe;Research Support, Non-U.S. Gov't;Embryonic and Fetal Development;review, tutorial;Humans;24 Pubmed search results 2008;review;Infant, Newborn}, Medline = {91246714}, Nlm_Id = {0376441}, Organization = {Department of Anatomy, Medical Faculty, University of Zagreb, Yugoslavia.}, Pages = {185-222}, Pubmed = {2094894}, Title = {Neuronal development in human prefrontal cortex in prenatal and postnatal stages}, Uuid = {DE93A028-EFB6-4D0B-A7BD-F644FCECF31E}, Volume = {85}, Year = {1990}} @article{Muccioli:2007, Abstract = {The endocannabinoids (eCBs) anandamide and 2-arachidonoyl glycerol (2-AG) are inactivated by a two-step mechanism. First, they are carried into cells, and then anandamide is hydrolyzed by fatty acid amide hydrolase (FAAH) and 2-AG by monoacylglycerol lipase (MGL). Here we provide evidence for a previously undescribed MGL activity expressed by microglial cells. We found that the mouse microglial cell line BV-2 does not express MGL mRNA and yet efficiently hydrolyzes 2-AG. URB597 (3'-carbamoyl-biphenyl-3-yl-cyclohexylcarbamate) reduces this hydrolysis by 50\%, suggesting the involvement of FAAH. The remaining activity is blocked by classic MGL inhibitors [[1,1-biphenyl]-3-yl-carbamic acid, cyclohexyl ester (URB602) and MAFP (methylarachidonyl fluorophosphate)] and is unaffected by inhibitors of COXs (cyclooxygenases), LOXs (lipooxygenases), and DGLs (diacylglycerol lipases), indicating the involvement of a novel MGL activity. Accordingly, URB602 leads to selective accumulation of 2-AG in intact BV-2 cells. Although MGL expressed in neurons is equally distributed between the cytosolic, mitochondrial, and nuclear fractions, the novel MGL activity expressed by BV-2 cells is enriched in mitochondrial and nuclear fractions. A screen for novel inhibitors of eCB hydrolysis identified several compounds that differentially block MGL, FAAH, and the novel MGL activity. Finally, we provide evidence for expression of the novel MGL by mouse primary microglia in culture. Our results suggest the presence of a novel, pharmacologically distinct, MGL activity that controls 2-AG levels in microglia.}, Author = {Muccioli, Giulio G. and Xu, Cong and Odah, Emma and Cudaback, Eiron and Cisneros, Jose Antonio and Lambert, Didier M. and L{\'o}pez Rodr{\'\i}guez, Mar{\'\i}a Luz and Bajjalieh, Sandra and Stella, Nephi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:28 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;11 Glia;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8102140}, Number = {11}, Organization = {Department of Pharmacology, University of Washington, Seattle, Washington 98195-7280, USA.}, Pages = {2883-9}, Pii = {27/11/2883}, Pubmed = {17360910}, Title = {Identification of a novel endocannabinoid-hydrolyzing enzyme expressed by microglial cells}, Uuid = {A068ADA7-7F54-48AE-9B8D-5826C96F1115}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4830-06.2007}} @article{Mueller:2003, Abstract = {Whereas local microglial cells of the CNS rapidly respond to injury, little is known about the functional role of resident macrophages of the peripheral nervous system in nerve pathology. Using bone marrow chimeric rats, we recently identified individual resident endoneurial macrophages that rapidly became activated after nerve injury. However, the extent of local macrophage activation and its quantitative contribution to the total macrophage response is unknown. We now have created chimeric mice by transplanting bone marrow from green fluorescent protein (GFP)-transgenic mice into irradiated wild-type mice, allowing easy differentiation and quantification of hematogenous and resident endoneurial macrophages. After sciatic nerve crush injury, both GFP(-) and GFP(+) resident macrophages, the latter having undergone physiological turnover from the blood before injury, rapidly underwent morphological alterations and increased in number. Proliferating GFP(-) and GFP(+) resident macrophages were abundant and peaked 3 days after injury. A major lesion-induced influx of hematogenous macrophages with a disproportionate increase of GFP(+) macrophages was not observed until Day 4. Throughout all time points examined, GFP(-) resident macrophages were strikingly frequent, reaching maximum numbers 9.5-fold above baseline. There was also a notable proportion of GFP(-) resident endoneurial macrophages phagocytosing myelin and expressing major histocompatibility complex class II. Our results demonstrate for the first time that the rapid response of resident endoneurial macrophages to nerve injury is quantitatively important and that local macrophages contribute significantly to the total endoneurial macrophage pool during Wallerian degeneration.}, Author = {Mueller, Marcus and Leonhard, Christine and Wacker, Karin and Ringelstein, E. Bernd and Okabe, Masaru and Hickey, William F. and Kiefer, Reinhard}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0023-6837}, Journal = {Lab Invest}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Macrophages;Bone Marrow Transplantation;Apoptosis;Indicators and Reagents;Mice, Transgenic;Sciatic Nerve;Mice, Inbred C57BL;11 Glia;Cell Count;Green Fluorescent Proteins;Radiation Chimera;Wallerian Degeneration;Mice;Nerve Crush;Luminescent Proteins;Peripheral Nerves}, Medline = {22482723}, Month = {2}, Nlm_Id = {0376617}, Number = {2}, Organization = {Department of Neurology, Universit{\"a}tsklinikum M{\"u}nster, M{\"u}nster, Germany.}, Pages = {175-85}, Pubmed = {12594233}, Title = {Macrophage response to peripheral nerve injury: the quantitative contribution of resident and hematogenous macrophages}, Uuid = {76AC1DD9-052C-4BD6-B7A5-546BD0F54363}, Volume = {83}, Year = {2003}} @article{Mujtaba:1998, Abstract = {We have previously shown that interferon-tau (IFN-tau) pretreatment inhibits the development of both acute and chronic mouse experimental allergic encephalomyelitis (EAE), an animal model for the human demyelinating disease multiple sclerosis (MS). IFN-tau is a type I IFN that has pregnancy recognition hormone activity in ruminants. Here we show that IFN-tau induced remission in SJL/J mice that had ongoing chronic active EAE disease and protected mice against secondary relapses. IFN-tau treatment reversed lymphocyte infiltration and microglial activation in the central nervous system. Mice that were treated with IFN-tau had lower levels of anti-MBP antibodies than untreated mice in both chronic and acute forms of EAE. MBP induced proliferation in B cells from EAE mice, but treatment with IFN-tau either in vivo or in vitro blocked activation. Furthermore, IFN-tau inhibited MBP activation of T cells from EAE mice. Thus, IFN-tau inhibits the humoral arm as well as the cellular arm of the autoimmune disease EAE. The data presented here show that IFN-tau inhibits both B cell and T cell responses in EAE as well as active, chronic EAE, and this may help explain the effectiveness of type I IFNs in treatment of MS.}, Author = {Mujtaba, M. G. and Streit, W. J. and Johnson, H. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0008-8749}, Journal = {Cell Immunol}, Keywords = {T-Lymphocytes;Animals;Encephalomyelitis, Experimental Autoimmune;Paralysis;Interferon Type I;Myelin Basic Proteins;Microglia;Antibody Formation;Sheep;B-Lymphocytes;Not relevant;11 Glia;Antibodies;Cell Line;Cattle;Immunity, Cellular;Pregnancy Proteins;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Recurrence}, Medline = {98330574}, Month = {6}, Nlm_Id = {1246405}, Number = {2}, Organization = {Department of Microbiology, University of Florida, Gainesville 32611, USA.}, Pages = {94-102}, Pii = {S0008874998913004}, Pubmed = {9665751}, Title = {IFN-tau suppresses both the autoreactive humoral and cellular immune responses and induces stable remission in mice with chronic experimental allergic encephalomyelitis}, Uuid = {5C78D478-4FAD-4CC4-AFAA-14257F725385}, Volume = {186}, Year = {1998}} @article{Mullen:1992, Abstract = {A battery of monoclonal antibodies (mAbs) against brain cell nuclei has been generated by repeated immunizations. One of these, mAb A60, recognizes a vertebrate nervous system- and neuron-specific nuclear protein that we have named NeuN (Neuronal Nuclei). The expression of NeuN is observed in most neuronal cell types throughout the nervous system of adult mice. However, some major cell types appear devoid of immunoreactivity including cerebellar Purkinje cells, olfactory bulb mitral cells, and retinal photoreceptor cells. NeuN can also be detected in neurons in primary cerebellar cultures and in retinoic acid-stimulated P19 embryonal carcinoma cells. Immunohistochemically detectable NeuN protein first appears at developmental timepoints which correspond with the withdrawal of the neuron from the cell cycle and/or with the initiation of terminal differentiation of the neuron. NeuN is a soluble nuclear protein, appears as 3 bands (46-48 x 10(3) M(r)) on immunoblots, and binds to DNA in vitro. The mAb crossreacts immunohistochemically with nervous tissue from rats, chicks, humans, and salamanders. This mAb and the protein recognized by it serve as an excellent marker for neurons in the central and peripheral nervous systems in both the embryo and adult, and the protein may be important in the determination of neuronal phenotype.}, Author = {Mullen, R. J. and Buck, C. R. and Smith, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {10 Development;Animals;Nervous System;Brain;23 Technique;Immunoblotting;01 Adult neurogenesis general;Research Support, U.S. Gov't, P.H.S.;Brain Chemistry;Antibodies, Monoclonal;Neurons;Cell Nucleus;Nuclear Proteins;24 Pubmed search results 2008;Immunohistochemistry;Nerve Tissue Proteins;Biological Markers;Vertebrates}, Medline = {93130769}, Month = {9}, Nlm_Id = {8701744}, Number = {1}, Organization = {Department of Anatomy, University of Utah School of Medicine, Salt Lake City 84132.}, Pages = {201-11}, Pubmed = {1483388}, Title = {NeuN, a neuronal specific nuclear protein in vertebrates}, Uuid = {B1852397-B1C4-41B1-8224-E56CDB663096}, Volume = {116}, Year = {1992}} @article{Muller:1977, Abstract = {The rational design of antitumor and antiviral agents must ultimately take advantage of biochemical differences between normal host cells and transformed cells. The initial experiments must be performed with subcellular or cellular model systems. For the studies with arabinosyl nucleosides we have chosen those enzyme systems, synthesizing DNA and RNA; being precursor analogues, the different arabinosyl nucleosides have been added in the triphosphate state to the different DNA- and RNA polymerase assays. 1-beta-D-Arabinofuranosylcytosine-5'-triphosphate has been found to inhibit the RNA-dependent DNA polymerases (isolated from oncogenic RNA viruses) 200-fold more sensitively than viral and cellular DNA-dependent DNA polymerases. Recent results, showing that RNA-leukemia-virus-related sequences are present in DNA of some human leukemia patients might support the assumption that the efficacy of this antimetabolite in the treatment of acute leukemia is due to its, at least relative selective inhibitory activity on reverse transcriptase. 9-beta-D-Arabinofuranosyladenine-5'-triphosphate is a strong inhibitor of cellular DNA polymerases with the cytological consequence of an inhibition of cell proliferation. The clinical benefit of the compound in treatment of tumors is dependent on their levels of adenosine deaminase. The triphosphate of this compound is a 100-fold more sensitive inhibitor of the herpesvirus DNA polymerase compared to the cellular replicative DNA polymerase. In addition the analogue, incorporated into herpesvirus DNA, acts as chain terminator. These effects are the biochemical basis for the highly selective antiherpesvirus activity of this antimetabolite. The anomer 9-alpha-D-arabinofuranosyladenine-5'-triphosphate only inhibits cellular replicative DNA polymerase and has no effect on herpesvirus DNA polymerase. Consequently this agent acts only cytostatically and not antivirally. Concerning 1-beta-D-arabinofuranosyluracil and 1-beta-D-arabinofuranosylthymine no pronounced antitumor or antiviral effect is known. 0368-2781 Journal Article}, Author = {Muller, W. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Jpn J Antibiot}, Keywords = {Nucleosides/isolation &purification/*pharmacology;Rabbits;Animals;Cells, Cultured;Vidarabine/pharmacology/therapeutic use;Herpesviridae;DNA-Directed DNA Polymerase/antagonists &inhibitors;Virus Diseases/drug therapy;Models, Biological;DNA-Directed RNA Polymerases/antagonists &inhibitors;Arabinose/pharmacology/therapeutic use;Cytarabine/pharmacology/therapeutic use;08 Aberrant cell cycle;Chemistry;*Antineoplastic Agents;Research Design;*Antiviral Agents;Mice;EE abstr}, Pages = {104-20}, Pubmed = {612702}, Title = {Rational design of arabinosyl nucleosides as antitumor and antiviral agents}, Uuid = {5CBB1B60-4ECD-4CF8-94D6-7538D3C10549}, Volume = {30 Suppl}, Year = {1977}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=612702}} @article{Muller:1996, Abstract = {Hippocampal organotypic slice cultures maintained 10-20 days in vitro express a high level of the polysialylated embryonic form of neural cell adhesion molecule (NCAM) (PSA-NCAM). Treatment of the cultures with endoneuraminidase-N selectively removed polysialic acid (PSA) from NCAM and completely prevented induction of long-term potentiation (LTP) and long-term depression (LTD) without affecting cellular or synaptic parameters. Similarly, slices prepared from transgenic mice lacking the NCAM gene exhibited a decaying LTP. No inhibition of N-methyl-D-aspartic acid receptor-dependent synaptic responses was detected. Washout of the enzyme resulted in reexpression of PSA immunoreactivity which correlated with a complete recovery of LTP and LTD. This reexpression was blocked by TTX and low calcium and enhanced by bicuculline. Taken together, these results indicate that neuronal activity regulates the expression of PSA-NCAM at the synapse and that this expression is required for the induction of synaptic plasticity.}, Author = {Muller, D. and Wang, C. and Skibo, G. and Toni, N. and Cremer, H. and Calaora, V. and Rougon, G. and Kiss, J. Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Long-Term Potentiation;Neural Cell Adhesion Molecules;Electrophysiology;Microscopy, Immunoelectron;Synapses;Animals;Rats;Neuronal Plasticity;N-Acetylneuraminic Acid;Mice, Mutant Strains;Glycoside Hydrolases;Rats, Sprague-Dawley;Hippocampus;Organ Culture Techniques;Animals, Newborn;Mice;Immunohistochemistry;Receptors, N-Methyl-D-Aspartate;24 Pubmed search results 2008;Neural Inhibition;Research Support, Non-U.S. Gov't}, Medline = {96413551}, Month = {9}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Morphology Centre M{\'e}dical Universitaire, Geneva, Switzerland.}, Pages = {413-22}, Pii = {S0896-6273(00)80174-9}, Pubmed = {8816705}, Title = {PSA-NCAM is required for activity-induced synaptic plasticity}, Uuid = {DDCCF3A8-4A20-44A3-9C6B-8C1657AD3728}, Volume = {17}, Year = {1996}} @article{Munirathinam:1997, Abstract = {Neuronal regeneration following early postnatal olfactory tract transection (OTS) was investigated in newborn Wistar rats. Olfactory tract lesioned rats were sacrificed at different time periods and the brains processed for Nissl staining. This was used to study the neural cell architecture; fiber tracts (myelinated fibers) were examined with Luxol Fast Blue staining. In addition, a neuronal tracing technique (i.e., retrograde labeling) was employed to study the reestablishment of connections with the target sites following transection of the tract. Degeneration of the olfactory tract was evident at the 7th day following lesion. Regeneration of the tract was not apparent even up to 60 days following transection. However, by 240 days, the olfactory tract had regenerated and the tract fibers had reestablished connection. This was confirmed by retrograde labeling of mitral cells of the olfactory bulb with Fast Blue (FB) injected into the piriform cortex, the target site of these neurons. In this study, we show that mammalian olfactory tract can regenerate spontaneously if the olfactory tract is lesioned neonatally. The results suggest that the olfactory tract is an excellent model to investigate some issues related to central nervous system regeneration.}, Author = {Munirathinam, S. and Rao, M. S. and Mohan, Y. R. and Raju, T. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Dyes;Indoles;Olfactory Pathways;Nerve Degeneration;Nerve Regeneration;Rats;Female;Time Factors;Rats, Wistar;Fluorescent Dyes;Denervation;Animals, Newborn;Male;Animals;24 Pubmed search results 2008;Central Nervous System Diseases;Amidines}, Medline = {97271217}, Month = {3}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Neurophysiology, National Institute of Mental Health and Neuro Sciences, Bangalore, India.}, Pages = {174-82}, Pii = {S0014488697964190}, Pubmed = {9126168}, Title = {Regeneration of the olfactory tract following neonatal lesion in rats}, Uuid = {B1DE1A5A-68E0-4516-9806-8A5B6B75EE57}, Volume = {144}, Year = {1997}} @article{Munoz-Elias:2004, Abstract = {We recently differentiated adult rat and human bone marrow stromal cells (MSCs) into presumptive neurons in cell culture. To determine whether the MSCs assume neuronal functions in vivo, we now characterize for the first time engraftment, migration, phenotypic expression, and long-term survival after infusion into embryonic day 15.5 (E15.5) rat ventricles in utero. By E17.5, donor cells formed discrete spheres in periventricular germinal zones, suggesting preferential sites of engraftment. The cells expressed progenitor vimentin and nestin but not mature neuronal markers. By E19.5, a subset assumed elongated migratory morphologies apposed to radial nestin-positive fibers running through the cortical white matter and plate, suggesting migration along radial glial processes. Cells remaining in germinal zones extended long, vimentin-positive fibers into the parenchyma, suggesting that the MSCs generated both migratory neurons and guiding radial glia. Consistent with this suggestion, >50\%of cultured mouse MSCs expressed the neuroprecursor/radial glial protein RC2. From E19.5 to postnatal day 3, MSCs populated distant areas, including the neocortices, hippocampi, rostral migratory stream, and olfactory bulbs. Whereas donor cells confined to the subventricular zone continued to express nestin, cells in the neocortex and midbrain expressed mature neuronal markers. The donor cells survived for at least 2 months postnatally, the longest time examined. Confocal analysis revealed survival of thousands of cells per cubic millimeter in the frontal cortex and olfactory bulb at 1 month. In the cortex and bulb, 98.6 and 77.3\%were NeuN (neuronal-specific nuclear protein) positive, respectively. Our observations suggest that transplanted adult MSCs differentiate in a regionally and temporally specific manner.}, Author = {Mu\~{n}oz-Elias, Guillermo and Marcus, Akiva J. and Coyne, Thomas M. and Woodbury, Dale and Black, Ira B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Survival;Cell Differentiation;Animals;Cells, Cultured;Frontal Lobe;Rats;Neuronal Plasticity;Phenotype;Brain;Antigens, Differentiation;Female;Vimentin;Rats, Sprague-Dawley;Cell Movement;08 Aberrant cell cycle;Time Factors;Olfactory Bulb;Research Support, U.S. Gov't, P.H.S.;Bone Marrow Cells;Neurons;Intermediate Filament Proteins;Neuroglia;Graft Survival;Nerve Tissue Proteins;Stromal Cells;Research Support, Non-U.S. Gov't}, Month = {5}, Nlm_Id = {8102140}, Number = {19}, Organization = {Department of Neuroscience and Cell Biology and the Stem Cell Research Center, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.}, Pages = {4585-95}, Pii = {24/19/4585}, Pubmed = {15140930}, Title = {Adult bone marrow stromal cells in the embryonic brain: engraftment, migration, differentiation, and long-term survival}, Uuid = {37E71A42-D3B2-11D9-A0E9-000D9346EC2A}, Volume = {24}, Year = {2004}, url = {papers/Munoz-Elias_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5060-03.2004}} @article{Munoz-Elias:2003, Abstract = {To define relationships among marrow stromal cells (MSCs), multipotential progenitors, committed precursors, and derived neurons, we examined differentiation, mitosis, and apoptosis in vitro. Neural induction medium morphologically converted over 70\%of MSCs to typical neurons, which expressed tau, neuronal nuclear antigen, neuron-specific enolase, and TUC-4 within 24 hours. A subset decreased fibronectin expression, consistent with mesenchymal to neuroectodermal conversion. More than 35\%of differentiating neurons incorporated bromodeoxyuridine (BrdU) and divided, increasing cell number by 60\%, while another subpopulation differentiated without incorporating BrdU or dividing. Inhibition of mitosis and DNA synthesis did not prevent neural differentiation, with 70\%of blocked cells expressing tau and displaying neuronal morphologies. By deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, less than 1\%of cells underwent apoptosis at 36 and 72 hours, suggesting differentiation without cell-selective mechanisms. Apparently, MSCs may directly differentiate into neurons without passing through a mitotic stage, suggesting that distinctions among stem cells, progenitors, and precursors are more flexible than formerly recognized.}, Author = {Mu\~{n}oz-El{\'\i}as, Guillermo and Woodbury, Dale and Black, Ira B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {Cell Differentiation;Animals;Rats;Phenotype;DNA;Apoptosis;Female;Mitosis;Rats, Sprague-Dawley;08 Aberrant cell cycle;Time Factors;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Fibronectins;In Situ Nick-End Labeling;Neurons;Immunohistochemistry;Bromodeoxyuridine;Stromal Cells;Biotin;Research Support, Non-U.S. Gov't}, Medline = {22717324}, Nlm_Id = {9304532}, Number = {4}, Organization = {University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway 08854, USA.}, Pages = {437-48}, Pubmed = {12832697}, Title = {Marrow stromal cells, mitosis, and neuronal differentiation: stem cell and precursor functions}, Uuid = {D7682BB3-8686-4877-8E42-B109E2D96B1B}, Volume = {21}, Year = {2003}, url = {papers/Munoz-Elías_StemCells2003.pdf}} @article{Muotri:2005, Abstract = {Revealing the mechanisms for neuronal somatic diversification remains a central challenge for understanding individual differences in brain organization and function. Here we show that an engineered human LINE-1 (for long interspersed nuclear element-1; also known as L1) element can retrotranspose in neuronal precursors derived from rat hippocampus neural stem cells. The resulting retrotransposition events can alter the expression of neuronal genes, which, in turn, can influence neuronal cell fate in vitro. We further show that retrotransposition of a human L1 in transgenic mice results in neuronal somatic mosaicism. The molecular mechanism of action is probably mediated through Sox2, because a decrease in Sox2 expression during the early stages of neuronal differentiation is correlated with increases in both L1 transcription and retrotransposition. Our data therefore indicate that neuronal genomes might not be static, but some might be mosaic because of de novo L1 retrotransposition events.}, Author = {Muotri, Alysson R. and Chu, Vi T. and Marchetto, Maria C. N. and Deng, Wei and Moran, John V. and Gage, Fred H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Cell Differentiation;Research Support, N.I.H., Extramural;24 Pubmed search results 2008;Green Fluorescent Proteins;Mosaicism;Animals;Cells, Cultured;Brain;Transcription, Genetic;Research Support, U.S. Gov't, P.H.S.;15 Retrovirus mechanism;Promoter Regions (Genetics);Transcription Factors;Molecular Sequence Data;RNA, Messenger;15 ERVs retroelements;DNA-Binding Proteins;Retroelements;Gene Expression Regulation;Cell Lineage;Rats;Long Interspersed Nucleotide Elements;HMGB Proteins;Recombination, Genetic;Mice;Stem Cells;Research Support, Non-U.S. Gov't;Neurons;Humans;Mice, Transgenic;Nerve Tissue Proteins}, Month = {6}, Nlm_Id = {0410462}, Number = {7044}, Organization = {Laboratory of Genetics, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.}, Pages = {903-10}, Pii = {nature03663}, Pubmed = {15959507}, Title = {Somatic mosaicism in neuronal precursor cells mediated by L1 retrotransposition}, Uuid = {5AC0AB3A-6C70-442F-9B17-4C32198FCFAA}, Volume = {435}, Year = {2005}, url = {papers/Muotri_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03663}} @article{Murai:2004, Abstract = {Compelling new findings have revealed that receptor tyrosine kinases of the Eph family, along with their ephrin ligands, play an essential role in regulating the properties of developing mature excitatory synapses in the central nervous system. The cell surface localization of both the Eph receptors and the ephrins enables these proteins to signal bidirectionally at sites of cell-to-cell contact, such as synapses. Eph receptors and ephrins have indeed been implicated in multiple aspects of synaptic function, including clustering and modulating N-methyl-D-aspartate receptors, modifying the geometry of postsynaptic terminals, and influencing long-term synaptic plasticity and memory. In this review, we discuss how Eph receptors and ephrins are integrated into the molecular machinery that supports synaptic function.}, Author = {Murai, Keith K. and Pasquale, Elena B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1073-8584}, Journal = {Neuroscientist}, Keywords = {10 Development;Animals;Synapses;Humans;Ephrins;Neuronal Plasticity;Neural Pathways;Synaptic Transmission;Receptors, Eph Family;review;research support, non-u.s. gov't;10 circuit formation;research support, u.s. gov't, p.h.s.;Central Nervous System;Receptors, N-Methyl-D-Aspartate;24 Pubmed search results 2008;research support, u.s. gov't, non-p.h.s.;Receptor Aggregation}, Month = {8}, Nlm_Id = {9504819}, Number = {4}, Organization = {Centre for Research in Neuroscience, McGill University Health Centre, Montreal General Hospital, Montreal, Canada.}, Pages = {304-14}, Pubmed = {15271258}, Title = {Eph receptors, ephrins, and synaptic function}, Uuid = {7120037A-5024-483B-A5FC-258E5A60A751}, Volume = {10}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1177/1073858403262221}} @article{Muraille:2001, Abstract = {The germinative ventricular zone of embryonic brain contains neural lineage progenitor cells that give rise to neurons, astrocytes and oligodendrocytes. The ability to generate neurons persists at adulthood in restricted brain areas. During development, many growth factors exert their effects by interacting with tyrosine kinase receptors and activate the phosphatidylinositol 3-kinase and the Ras/MAP kinase pathways. By its ability to modulate these pathways, the recently identified Src homology 2 domain-containing inositol polyphosphate 5- phosphatase 2, SHIP2, has the potential to regulate neuronal development. Using in situ hybridization technique with multiple synthetic oligonucleotides, we demonstrated that SHIP2 mRNA was highly expressed in the ventricular zone at early embryonic stages and subventricular zones at latter stages of brain and spinal cord and in the sympathetic chain. No significant expression was seen in differentiated fields. This restricted expression was maintained from embryonic day 11.5 to birth. In the periphery, large expression was detected in muscle and kidney and moderate expression in thyroid, pituitary gland, digestive system and bone. In the adult brain, SHIP2 was mainly restricted in structures containing neural stem cells such as the anterior subventricular zone, the rostral migratory stream and the olfactory tubercle. SHIP2 was also detected in the choroid plexuses and the granular layer of the cerebellum. The specificity of SHIP2 expression in neural stem cells was further demonstrated by (i) the dramatic increase in SHIP2 mRNA signal in neural cell adhesion molecule (N-CAM)-deficient mice, which present an accumulation of progenitor cells in the anterior subventricular zone and the rostral migratory stream, (ii) the abundant expression of 160-kDa SHIP2 by western blotting in proliferating neurospheres in culture and its downregulation in non-proliferating differentiated neurospheres.In conclusion, the close correlation between the pattern of SHIP2 expression in the brain and the proliferative and early differentiative events suggests that the phosphatase SHIP2 may have important roles in neural development. Using Smart Source Parsing}, Author = {Muraille, E. and Dassesse, D. and Vanderwinden, J. M. and Cremer, H. and Rogister, B. and Erneux, C. and Schiffmann, S. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Neuroscience}, Keywords = {C pdf;04 Adult neurogenesis factors}, Number = {4}, Pages = {1019-30}, Title = {The SH2 domain-containing 5-phosphatase SHIP2 is expressed in the germinal layers of embryo and adult mouse brain: increased expression in N-CAM-deficient mice}, Uuid = {188E89B6-95A6-4CA4-B27E-7A3FCC1A15EF}, Volume = {105}, Year = {2001}, url = {papers/Muraille_Neuroscience2001}} @article{Murase:2002, Abstract = {Macrophage colony stimulating factor (M-CSF) is known to be the most effective growth factor for macrophage and microglial proliferation. In the brain tissue system, M-CSF is mainly produced in astrocytes and microglia, but is not known to occur in neurons. In the present paper, we examined the distribution of neurons expressing M-CSF in the mouse brain by immunohistochemistry and in situ hybridization. We observed M-CSF immunoreactivity in both the cerebellum and the olfactory bulb. These positive cells were found to be Purkinje cells in the cerebellum, and mitral cells in the olfactory bulb. M-CSF mRNA expression was also confirmed to occur in these cells. Purkinje cells of reeler and weaver mutants showed M-CSF expression as seen in wild-type mice; however, those in the staggerer mutant did not. This expression in wild-type mice first appeared at postnatal day 7 and continued stably thereafter. When Purkinje cells were deprived of their climbing fibre innervation by inferior cerebellar pedunculotomy or by transplantation of cerebellar anlagen into the anterior eye chamber, the expression of M-CSF remained unchanged. These data indicate that expression of M-CSF in Purkinje cells is controlled by an intrinsic mechanism and could, therefore, be a new marker of postnatal development in rodent cerebella. The absence of M-CSF expression in the staggerer mutant is possibly due to developmental arrest in the early postnatal period.}, Author = {Murase, Shin-ichi and Hayashi, Yokichi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0018-2214}, Journal = {Histochem J}, Keywords = {Purkinje Cells;Animals;Mutation;RNA, Messenger;11 Glia;Mice, Neurologic Mutants;Male;Embryo;Olfactory Bulb;In Situ Hybridization;Fetal Tissue Transplantation;Blotting, Western;Neurons;Macrophage Colony-Stimulating Factor;Mice;Cerebellum;24 Pubmed search results 2008;Immunohistochemistry;Nerve Fibers}, Medline = {22251859}, Nlm_Id = {0163161}, Number = {1-2}, Organization = {Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.}, Pages = {85-95}, Pubmed = {12365804}, Title = {Neuronal expression of macrophage colony stimulating factor in Purkinje cells and olfactory mitral cells of wild-type and cerebellar-mutant mice}, Uuid = {0526A742-563B-4381-926A-56CFD8B9C665}, Volume = {34}, Year = {2002}} @article{Murayama:2007, Abstract = {Calcium influx into the dendritic tufts of layer 5 neocortical pyramidal neurons modifies a number of important cellular mechanisms. It can trigger local synaptic plasticity and switch the firing properties from regular to burst firing. Due to methodological limitations, our knowledge about Ca2+ spikes in the dendritic tuft stems mostly from in vitro experiments. However, it has been speculated that regenerative Ca2+ events in the distal dendrites correlate with distinct behavioral states. Therefore it would be most desirable to be able to record these Ca2+ events in vivo, preferably in the behaving animal. Here, we present a novel approach for recording Ca2+ signals in the dendrites of populations of layer 5 pyramidal neurons in vivo, which ensures that all recorded fluorescence changes are due to intracellular Ca2+ signals in the apical dendrites. The method has two main features: 1) bolus loading of layer 5 with a membrane-permeant Ca2+ dye resulting in specific loading of pyramidal cell dendrites in the upper layers and 2) a fiberoptic cable attached to a gradient index lens and a prism reflecting light horizontally at 90 degrees to the angle of the apical dendrites. We demonstrate that the in vivo signal-to-noise ratio recorded with this relatively inexpensive and easy-to-implement fiberoptic-based device is comparable to conventional camera-based imaging systems used in vitro. In addition, the device is flexible and lightweight and can be used for recording Ca2+ signals in the distal dendritic tuft of freely behaving animals.}, Author = {Murayama, Masanori and P{\'e}rez-Garci, Enrique and L{\"u}scher, Hans-Rudolf R. and Larkum, Matthew E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {0375404}, Number = {3}, Organization = {Institute of Physiology, University of Bern, B{\"u}hlplatz 5, CH-3012 Bern, Switzerland.}, Pages = {1791-805}, Pii = {00082.2007}, Pubmed = {17634346}, Title = {Fiberoptic system for recording dendritic calcium signals in layer 5 neocortical pyramidal cells in freely moving rats}, Uuid = {FAD54FA7-BD69-4061-B02C-9D364FFFE0CE}, Volume = {98}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00082.2007}} @article{Murray:2004, Abstract = {I discuss advances in the cell cycle in the 21 years since cyclin was discovered. The surprising redundancy amongst the classical cyclins (A, B, and E) and cyclin-dependent kinases (Cdk1 and Cdk2) show that the important differences between these proteins are when and where they are expressed rather than the proteins they phosphorylate. Although the broad principles of the cell cycle oscillator are widely accepted, we are surprisingly ignorant of its detailed mechanism. This is especially true of the anaphase promoting complex (APC), the machine that triggers chromosome segregation and the exit of mitosis by targeting securin and mitotic cyclins for destruction. I discuss how a cyclin/Cdk-based engine could have evolved to assume control of the cell cycle from other, older protein kinases. 0092-8674 Journal Article Review Review, Academic}, Author = {Murray, A. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Cell}, Keywords = {Models, Biological;EE pdf;*Cell Cycle;Mitotic Spindle Apparatus/physiology;Human;08 Aberrant cell cycle;Time Factors;Support, U.S. Gov't, P.H.S.;Mitosis;Animals;Phosphorylation;Cyclins/*physiology}, Number = {2}, Organization = {Department of Molecular and Cellular Biology, Biological Laboratories, Harvard University, Cambridge, MA 02138, USA. amurray\@mcb.harvard.edu}, Pages = {221-34}, Title = {Recycling the cell cycle: cyclins revisited}, Uuid = {1452B089-5B68-482E-B1B9-42C8AE09B4C0}, Volume = {116}, Year = {2004}, url = {papers/Murray_Cell2004.pdf}} @article{Murrell:1999, Abstract = {The site for interactions between the nervous system and much of the chemical world is in the olfactory sensory neuron (OSN). Odorant receptor proteins (ORPs) are postulated to mediate these interactions. However, the function of most ORPs has not been demonstrated in vivo or in vitro. For this and other reasons, we created a conditionally immortalized cell line derived from the OSN lineage, which we term odora. Odora cells, under control conditions, are phenotypically similar to the OSN progenitor, the globose basal cell. After differentiation, odora cells more closely resemble OSNs. Differentiated odora cells express neuronal and olfactory markers, including components of the olfactory signal transduction pathway. Unlike other cell lines, they also efficiently target exogenous ORPs to their surface. Strikingly, differentiated odora cells expressing ORPs respond to odorants, as measured by an influx of calcium. In particular, cells expressing one ORP demonstrate a specific response to only one type of tested odorant. Odora cells, therefore, are ideal models to examine the genesis and function of olfactory sensory neurons.}, Author = {Murrell, J. R. and Hunter, D. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {J Neurosci}, Keywords = {13 Olfactory bulb anatomy;I;Cell Differentiation;Reverse Transcriptase Polymerase Chain Reaction;Rats;Cell Culture/methods;Cell Line;Signal Transduction;*Odors;Animal;Olfactory Mucosa/*cytology;Animals, Newborn;Support, Non-U.S. Gov't;Olfactory Receptor Neurons/*cytology/*physiology;Receptors, Odorant/*genetics/*physiology;Nerve Tissue Proteins/analysis;Ion Channels/*genetics}, Number = {19}, Organization = {Program in Cell, Molecular, and Developmental Biology, Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.}, Pages = {8260-70.}, Title = {An olfactory sensory neuron line, odora, properly targets olfactory proteins and responds to odorants}, Uuid = {583F42E2-B6C1-4D75-BBCB-7B347B1B361F}, Volume = {19}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10493727%20http://www.jneurosci.org/cgi/content/full/19/19/8260%20http://www.jneurosci.org/cgi/content/abstract/19/19/8260}} @article{Muller:2007, Abstract = {The chemokine receptor CXCR3 promotes the trafficking of activated T and NK cells in response to three ligands, CXCL9, CXCL10, and CXCL11. Although these chemokines are produced in the CNS in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), their role in the pathogenesis of CNS autoimmunity is unresolved. We examined the function of CXCR3 signaling in EAE using mice that were deficient for CXCR3 (CXCR3(-/-)). The time to onset and peak disease severity were similar for CXCR3(-/-) and wild-type (WT) animals; however, CXCR3(-/-) mice had more severe chronic disease with increased demyelination and axonal damage. The inflammatory lesions in WT mice consisted of well-demarcated perivascular mononuclear cell infiltrates, mainly in the spinal cord and cerebellum. In CXCR3(-/-) mice, these lesions were more widespread throughout the CNS and were diffused and poorly organized, with T cells and highly activated microglia/macrophages scattered throughout the white matter. Although the number of CD4(+) and CD8(+) T cells infiltrating the CNS were similar in CXCR3(-/-) and WT mice, Foxp3(+) regulatory T cells were significantly reduced in number and dispersed in CXCR3(-/-) mice. The expression of various chemokine and cytokine genes in the CNS was similar in CXCR3(-/-) and WT mice. The genes for the CXCR3 ligands were expressed predominantly in and/or immediately surrounding the mononuclear cell infiltrates. We conclude that in EAE, CXCR3 signaling constrains T cells to the perivascular space in the CNS and augments regulatory T cell recruitment and effector T cell interaction, thus limiting autoimmune-mediated tissue damage.}, Author = {M{\"u}ller, Marcus and Carter, Sally L. and Hofer, Markus J. and Manders, Peter and Getts, Daniel R. and Getts, Meghan T. and Dreykluft, Angela and Lu, Bao and Gerard, Craig and King, Nicholas J. C. and Campbell, Iain L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {research support, non-u.s. gov't;14 Immune;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {2985117R}, Number = {5}, Organization = {School of Molecular and Microbial Biosciences, School of Medical Sciences, University of Sydney, Sydney, Australia.}, Pages = {2774-86}, Pii = {179/5/2774}, Pubmed = {17709491}, Title = {CXCR3 signaling reduces the severity of experimental autoimmune encephalomyelitis by controlling the parenchymal distribution of effector and regulatory T cells in the central nervous system}, Uuid = {FBD7AAD8-4CA5-4DD8-8CDB-3313BCE7D3C6}, Volume = {179}, Year = {2007}} @article{Munch:2003, Abstract = {Activation of glial cells has been proposed to contribute to neuronal dysfunction and neuronal cell death in Alzheimer's disease. In this study, we attempt to determine some of the effects of secreted factors from activated murine N-11 microglia on viability and morphology of neurons using the differentiated neuroblastoma cell line Neuro2a. Microglia were activated either by lipopolysaccharide (LPS), bacterial cell wall proteoglycans, or advanced glycation endproducts (AGEs), protein-bound sugar oxidation products. At high LPS or AGE concentrations, conditioned medium from microglia caused neuronal cell death in a dose-dependent manner. At sublethal LPS or AGE concentrations, conditioned media inhibited retinoic acid-induced neurite outgrowth and stimulated retraction of already extended neurites. Among the many possible secreted factors, the contribution of NO or NO metabolites in the cytotoxicity of conditioned medium was investigated. Cell death and changes in neurite morphology were partly reduced when NO production was inhibited by nitric oxide synthase inhibitors. The results suggest that even in the absence of significant cell death, inflammatory processes, which are partly transmitted via NO metabolites, may affect intrinsic functions of neurons such as neurite extension that are essential components of neuronal morphology and thus may contribute to degenerative changes in Alzheimer's disease.}, Author = {M{\"u}nch, Gerald and Gasic-Milenkovic, Jovana and Dukic-Stefanovic, Sladjana and Kuhla, Bj{\"o}rn and Heinrich, Katrin and Riederer, Peter and Huttunen, Henri J. and Founds, Hank and Sajithlal, Gangadharan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Cell Survival;Dose-Response Relationship, Drug;Cell Differentiation;Neuroblastoma;Animals;Proteoglycans;Microglia;Lipopolysaccharides;Neurites;Culture Media, Conditioned;Not relevant;11 Glia;Support, Non-U.S. Gov't;Alzheimer Disease;Tumor Cells, Cultured;Gliosis;Mice;Inflammation;Nitric Oxide;Tretinoin;Cell Death;Glycosylation End Products, Advanced}, Medline = {22583643}, Month = {5}, Nlm_Id = {0043312}, Number = {1}, Organization = {Neuroimmunological Cell Biology Unit, Leipzig, Germany. mueg\@medizin.uni-leipzig.de}, Pages = {1-8}, Pubmed = {12698210}, Title = {Microglial activation induces cell death, inhibits neurite outgrowth and causes neurite retraction of differentiated neuroblastoma cells}, Uuid = {B15E5C36-3CED-42BB-9B67-4BC6D7E908BE}, Volume = {150}, Year = {2003}, url = {papers/Münch_ExpBrainRes2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00221-003-1389-5}} @article{Myme:2003, Abstract = {To better understand regulation of N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complements across the cortex, and to investigate NMDA receptor (NMDAR)-based models of persistent activity, we compared NMDA/AMPA ratios in prefrontal (PFC) and visual cortex (VC) in rat. Whole cell voltage-clamp responses were recorded in brain slices from layer 2/3 pyramidal cells of the medial PFC and VC of rats aged p16-p21. Mixed miniature excitatory postsynaptic currents (mEPSCs) having AMPA receptor (AMPAR)- and NMDAR-mediated components were isolated in nominally 0 Mg2+ ACSF. Averaged mEPSCs were well-fit by double exponentials. No significant differences in the NMDA/AMPA ratio (PFC: 27 +/- 1\%; VC: 28 +/- 3\%), peak mEPSC amplitude (PFC: 19.1 +/- 1 pA; VC: 17.5 +/- 0.7 pA), NMDAR decay kinetics (PFC: 69 +/- 8 ms; VC: 67 +/- 6 ms), or degree of correlation between NMDAR- and AMPAR-mediated mEPSC components were found between the areas (PFC: n = 27; VC: n = 28). Recordings from older rats (p26-29) also showed no differences. EPSCs were evoked extracellularly in 2 mM Mg2+ at depolarized potentials; although the average NMDA/AMPA ratio was larger than that observed for mEPSCs, the ratio was similar in the two regions. In nominally 0 Mg2+ and in the presence of CNQX, spontaneous activation of NMDAR increased recording noise and produced a small tonic depolarization which was similar in both areas. We conclude that this basic property of excitatory transmission is conserved across PFC and VC synapses and is therefore unlikely to contribute to differences in firing patterns observed in vivo in the two regions.}, Author = {Myme, Chaelon I. O. and Sugino, Ken and Turrigiano, Gina G. and Nelson, Sacha B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Visual Cortex;research support, u.s. gov't, p.h.s. ;Excitatory Postsynaptic Potentials;21 Neurophysiology;Rats;Prefrontal Cortex;Rats, Long-Evans;Receptors, AMPA;Electrophysiology;Animals;Patch-Clamp Techniques;Receptors, N-Methyl-D-Aspartate;Excitatory Amino Acid Antagonists;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0375404}, Number = {2}, Organization = {Department of Biology, Volen Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110, USA.}, Pages = {771-9}, Pii = {00070.2003}, Pubmed = {12672778}, Title = {The NMDA-to-AMPA ratio at synapses onto layer 2/3 pyramidal neurons is conserved across prefrontal and visual cortices}, Uuid = {65797E55-8EB3-4CCF-9141-D33F97A872E1}, Volume = {90}, Year = {2003}, url = {papers/Myme_JNeurophysiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00070.2003}} @article{Myslobodski:1968, Author = {Myslobodski, M. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0031-2991}, Journal = {Patol Fiziol Eksp Ter}, Keywords = {Epilepsy;21 Neurophysiology;Humans;24 Pubmed search results 2008;21 Epilepsy;review}, Medline = {70265267}, Nlm_Id = {0376421}, Number = {4}, Pages = {80-6}, Pubmed = {4915997}, Title = {[Provocation of epileptiform activity by physical factors]}, Uuid = {5F369D47-28AD-4FDA-A85C-80C228B8464F}, Volume = {12}, Year = {1968}} @article{Nacher:2001, Abstract = {Doublecortin (DCX) is a protein required for normal neuronal migration in the developing cerebral cortex, where it is widely expressed in both radially and tangentially migrating neuroblasts. Moreover, it has been observed in the adult rostral migratory stream, which contains the neuronal precursors traveling to the olfactory bulb. We have performed DCX immunocytochemistry in the adult rat brain to identify precisely the neuronal populations expressing this protein. Our observations confirm the presence of DCX immunoreactive cells with the characteristic morphology of migrating neuroblasts in the subventricular zone, rostral migratory stream and the main and accessory olfactory bulbs. We have also found putative migratory cells expressing DCX in regions were no adult neuronal migration has been described, as the corpus callosum, the piriform cortex layer III/endopiriform nucleus and the striatum. Surprisingly, many cells with the phenotype of differentiated neurons were DCX immunoreactive; e.g. certain granule neurons in the hilar border of the granular layer of the dentate gyrus, some neuronal types in the piriform cortex layer II, granule and periglomerular neurons in the main and accessory olfactory bulbs, and isolated cells in the striatum. Almost all DCX immunoreactive cells also express the polysialylated form of neural cell adhesion molecule and have a similar distribution to rat collapsin receptor-mediated protein-4, two molecules involved in neuronal structural plasticity. Given these results, we hypothesize that DCX expression in differentiated neurons could be related to its capacity for microtubule reorganization and that this fact could be linked to axonal outgrowth or synaptogenesis.}, Author = {Nacher, J. and Crespo, C. and McEwen, B. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Eur J Neurosci}, Keywords = {B pdf;02 Adult neurogenesis migration}, Number = {4}, Organization = {Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10021, USA; Neurobiology, Cell Biology Department, Universitat de Valencia, E-46100, Spain.}, Pages = {629-44.}, Title = {Doublecortin expression in the adult rat telencephalon}, Uuid = {0606CEF5-2480-4700-BC97-F5CFD2BD87E6}, Volume = {14}, Year = {2001}, url = {papers/Nacher_EurJNeurosci2001}} @article{Nacher:1999, Abstract = {Intraperitoneal injection of the neurotoxin 3-acetylpyridine (3AP) induces a rapid degeneration of the medial cerebral cortex (lizard fascia dentata) granular layer and of its zinc enriched axonal projection (lizard mossy fibres). After 6-8 weeks post-lesion the cell debris have been removed and the granular layer is repopulated by neurons generated in the subjacent ependyma. Both processes, neuron incorporation and debris removal, seem to be crucial for successful regeneration. Scavenging processes in the lesioned mammalian CNS are usually carried out by microglia and/or astrocytes. In the lizard cerebral cortex there are no free astrocytes and the only glial fibrillary acid (GFAP) immunoreactive cells are radial glia-ependymocytes, similar to those present during mammalian CNS development. Ependymocytes, in addition to their help in vertical migrations of just generated immature neurons, built the cortical glial scaffold, insulate the blood capillaries, form the outer glial limiting membrane, thus playing an essential role in the lizard cortical blood-brain barrier. In this study, by means of GFAP-immunocytochemistry and electron microscopy, we have shown that radial glial cells participate actively in the removal/phagocytosis of cellular debris generated in the lesion process: mainly degenerated synapses, but interestingly, also some neuronal somata. Cell debris taken up by ependymocyte lateral processes seem to be progressively transported to either distal (pial) or proximal (ventricular) poles of the cell, where they result in lipofuscin accumulations. The hypothetical subsequent exchange of debris from ependymoglia by microglia/macrophages and Kolmer cells is discussed.}, Author = {Nacher, J. and Ram{\'\i}rez, C. and Palop, J. J. and Molowny, A. and Luis de la Iglesia, J. A. and L{\'o}pez-Garc{\'\i}a, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0213-3911}, Journal = {Histol Histopathol}, Keywords = {Neuroglia;Glial Fibrillary Acidic Protein;Microscopy, Electron;Dentate Gyrus;Not relevant;Pyridines;Neurotoxins;11 Glia;Regeneration;Time Factors;Immunoenzyme Techniques;Lizards;Support, Non-U.S. Gov't;Animals;Cerebral Cortex}, Medline = {99142127}, Month = {1}, Nlm_Id = {8609357}, Number = {1}, Organization = {Faculty of Biological Sciences, University of Valencia, Spain.}, Pages = {89-101}, Pubmed = {9987654}, Title = {Radial glia and cell debris removal during lesion-regeneration of the lizard medial cortex}, Uuid = {91B44A68-3C6A-4B98-B516-6AF953CB9567}, Volume = {14}, Year = {1999}} @article{Nacher:2003, Abstract = {The production of new neurons declines during adulthood and persists, although at very low levels, in the aged hippocampus. Since neurogenesis in young adults has been related to learning and memory, its reduction may contribute to the age-related impairments in these abilities. Adrenalectomy (ADX) enhances neurogenesis in the aged hippocampus, although it also induces neuronal cell death. Since the administration of an NMDA receptor antagonist enhances neurogenesis in young adult rats without deleterious morphological effects, we have tested whether neurogenesis could be reactivated in aged rats. Our study shows that cell proliferation, cell death, neurogenesis and the number of radial glia-like nestin immunoreactive cells decrease in middle-age (10 months) and remain very low in the aged hippocampus. Injection of the NMDA receptor antagonist to aged rats increases significantly the number of proliferating cells, new neurons and radial glia-like cells in the hippocampus. 0197-4580 Journal Article}, Author = {Nacher, J. and Alonso-Llosa, G. and Rosell, D. R. and McEwen, B. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Neurobiol Aging}, Keywords = {Bromodeoxyuridine;Animals;Cell Survival/drug effects;Rats;Excitatory Amino Acid Antagonists/pharmacology;Female;Neurons/chemistry/*cytology;Receptors, N-Methyl-D-Aspartate/*antagonists &inhibitors;Adrenalectomy;Aging/*physiology;Nerve Tissue Proteins/analysis;Dentate Gyrus/*cytology;Antimetabolites;Rats, Inbred F344;Support, Non-U.S. Gov't;Neuropeptides/analysis;Support, U.S. Gov't, Non-P.H.S.;Cell Death/drug effects;Support, U.S. Gov't, P.H.S.;04 Adult neurogenesis factors;Immunohistochemistry;Biological Markers;C pdf;Neuroglia/cytology;Cell Division/drug effects;2-Amino-5-phosphonovalerate/*analogs &derivatives/pharmacology}, Number = {2}, Organization = {Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. nacher\@uv.es}, Pages = {273-84}, Pubmed = {12498961}, Title = {NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus}, Uuid = {10E00C3F-AABE-459B-9B27-DBE929973B7E}, Volume = {24}, Year = {2003}, url = {papers/Nacher_NeurobiolAging2003}} @article{Nacimiento:1995, Abstract = {Structural changes in lumbosacral ventral horn neurons and their synaptic input were studied at 3, 10, 21, 42, and 90 days following low thoracic cord hemisection in adult rats by light microscopic examination of synaptophysin immunoreactivity (SYN-IR) and by electron microscopy. There was an ipsilateral transient decrease in SYN-IR at the somal and proximal dendritic surfaces of anterior horn neurons which extended caudally from the site of injury over a postoperative (p.o.) period of 42 days. Concomitantly, at 21 days p.o., perineuronal SYN-IR started to recover in upper lumbar segments. By 90 days p.o., a normal staining pattern of SYN was noted in upper and mid lumbar segments, but the perineuronal SYN-IR was still slightly below normal levels in low lumbar and sacral segments. Electron microscopy revealed ultrastructural changes coincident with the alterations in SYN-IR. At 3 days p.o., phagocytosis of degenerating axon terminals by activated microglial cells was observed at the somal and proximal dendritic surfaces of ventral horn neurons. These changes were most prominent up to two segments caudal to the lesion. At 10 days p.o., advanced stages of bouton phagocytosis were still detectable in all lumbosacral motor nuclei. Additionally, abnormal axon terminals, with a few dispersed synaptic vesicles and accumulations of large mitochondria, appeared at the scalloped somal surfaces of anterior horn neurons. At 21 days p.o., several large lumbosacral motoneurons had developed chromatolysis-like ultrastructural alterations and motoneuronal cell bodies had become partially covered by astrocytic lamellae. At 42 days p.o., there was a transient appearance of polyribosomes in some M-type boutons. In addition, at 42 and 90 days p.o., a few degenerating motoneurons were detected in all lumbosacral segments, but most displayed normal neuronal cell bodies contacted by numerous intact synapses as well as by astrocytic processes. In contrast to these striking alterations of synaptic input at somal and proximal dendritic surfaces of motoneurons, relatively few degenerating boutons were detected in the neuropil of motor nuclei at all the p.o. times studied. We suggest that the preferential disturbance of the predominantly inhibitory axosomatic synapses on ventral horn neurons may be involved in the mechanisms which influence the well-established increase in motoneuronal excitability after spinal cord injury.}, Author = {Nacimiento, W. and Sappok, T. and Brook, G. A. and T{\'o}th, L. and Schoen, S. W. and Noth, J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Phagocytosis;Presynaptic Terminals;Animals;Synapses;Rats;Mitochondria;Female;Microglia;Synaptophysin;Fibrosis;Not relevant;11 Glia;Spinal Cord;Spinal Cord Injuries;Support, Non-U.S. Gov't;Neurons;Gliosis;Immunohistochemistry;Microscopy, Electron}, Medline = {96191752}, Nlm_Id = {0412041}, Number = {6}, Organization = {Depart of Neurology, Technical University, School of Medicine, Aachen, Germany.}, Pages = {552-64}, Pubmed = {8615075}, Title = {Structural changes of anterior horn neurons and their synaptic input caudal to a low thoracic spinal cord hemisection in the adult rat: a light and electron microscopic study}, Uuid = {DA99FEBA-9C42-420B-B7EC-2573C21766A1}, Volume = {90}, Year = {1995}} @article{Nadarajah:1997, Abstract = {Gap junctions are membrane channels that mediate the direct passage of ions and molecules between adjacent cells. Recent tracer coupling and optical recording studies have revealed the presence of gap junction-mediated communication between neurons during neocortical development. We have visualized gap junctions in the developing rat cerebral cortex with electron microscopy and studied the pattern of expression and cellular localization of connexins 26, 32, and 43 that take part in their formation. We found that these connexins (Cxs) are expressed differentially during development, and their patterns of expression are correlated with important developmental events such as cell proliferation, migration, and formation of cortical neuronal circuits. Specifically, we observed that the developmental profile of Cx 26 during the first 3 weeks of postnatal life matched closely the development of neuronal coupling, suggesting that coupled neurons use this gap junction protein during circuit formation in the cortex. The subsequent diminution of Cx 26 was mirrored by an increase in Cx 32 immunoreactivity, which became pronounced at the late stages of cortical maturation. In contrast, Cx 43 was localized in the cortex throughout the period of development. Its localization in radial glial fibers closely associated with migrating neurons suggests that this Cx may be involved in neuronal migration.}, Author = {Nadarajah, B. and Jones, A. M. and Evans, W. H. and Parnavelas, J. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Gap Junctions;research support, non-u.s. gov't;21 Neurophysiology;Female;Immunohistochemistry;Rats;21 Gap junctions;Pregnancy;Animals;Connexins;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8102140}, Number = {9}, Organization = {Department of Anatomy and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.}, Pages = {3096-111}, Pubmed = {9096144}, Title = {Differential expression of connexins during neocortical development and neuronal circuit formation}, Uuid = {97CB436E-CA41-44FF-AA32-DE5612D32211}, Volume = {17}, Year = {1997}} @article{Nadarajah:2002, Abstract = {It is believed that postmitotic neurons migrate away from their sites of origin in the germinal zones to populate distant targets. Contrary to this notion, we found, using time-lapse imaging of brain slices, populations of neurons positioned at various levels of the developing neocortex that migrate towards the cortical ventricular zone. After a pause in this proliferative zone, they migrate radially in the direction of the pial surface to take up positions in the cortical plate. Immunohistochemical analysis together with tracer labeling in brain slices showed that cells showing ventricle-directed migration in the developing cortex are GABAergic interneurons originating in the ganglionic eminence in the ventral telencephalon. We speculate that combinations of chemoattractant and chemorepellent molecules are involved in this ventricle-directed migration and that interneurons may seek the cortical ventricular zone to receive layer information. 1097-6256 Journal Article}, Author = {Nadarajah, B. and Alifragis, P. and Wong, R. O. and Parnavelas, J. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Nat Neurosci}, Keywords = {10 Development;Cerebral Ventricles/cytology/*embryology;Animals;In Vitro;Neocortex/cytology/*embryology;Rats;Cell Movement/*physiology;Microscopy, Confocal;Prosencephalon/cytology/embryology;F pdf;Time Factors;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Mice;Fluorescent Dyes/metabolism;Immunohistochemistry;Carboxylic Acids/metabolism;Interneurons/*physiology}, Number = {3}, Organization = {Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK.}, Pages = {218-24}, Pubmed = {11850632}, Title = {Ventricle-directed migration in the developing cerebral cortex}, Uuid = {DEF8CF75-AF80-4C0F-9E0E-CD4127C32876}, Volume = {5}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11850632}} @article{Nadler:1980, Abstract = {Degeneration of hippocampal CA3 pyramidal cells was investigated by light and electron microscopy after intraventricular injection of the potent convulsant, kainic acid. Electron microscopy revealed evidence of pyramidal cell degeneration within one hour. The earliest degenerative changes were confined to the cell body and proximal dendritic shafts. These included an increased incidence of lysosomal structures, deformation of the perikaryal and nuclear outlines, some increase in background electron density, and dilation of the cisternae of the endoplasmic reticulum accompanied by detachment of polyribosomes. Within the next few hours the pyramidal cells atrophied and became electron dense. Then these cells became electron lucent once more as ribosomes disappeared and their membranes and organelles broke up and disintegrated. Light microscopic changes correlated with these ultrastructural observations. The dendritic spines and the initial portion of the dendritic shaft became electron dense within four hours and degenerated rapidly, whereas the intermediate segment of the dendrites swelled moderately and became more electron lucent. No degenerative changes were evident in pyramidal cell axons and boutons until one day after kainic acid treatment. Less than one hour after kainic acid administration, astrocytes in the CA3 area swelled, initially in the vicinity of the cell body and mossy fiber layers. It is suggested that the paroxysmal discharges initiated in CA3 pyramidal cells by kainic acid served as the stimulus for this response. Phagocytosis commenced between one and three days after kainic acid administration, but remained incomplete at survival times of 6-8 weeks. Astrocytes, microglia, and probably oligodendroglia phagocytized the degenerating material. These results point to the pyramidal cell body and possibly also the dendritic spines as primary targets of kainic acid neurotoxicity. In conjunction with other data, they support the view that lesions made by intraventricular kainic acid can serve as models of epileptic brain damage.}, Author = {Nadler, J. V. and Perry, B. W. and Gentry, C. and Cotman, C. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Pyrrolidines;Synapses;Dendrites;Neuroglia;Nerve Degeneration;Hippocampus;Rats;Not relevant;11 Glia;Support, U.S. Gov't, Non-P.H.S.;Injections, Intraventricular;Kainic Acid;Support, U.S. Gov't, P.H.S.;Male;Animals;Neurons;Axons}, Medline = {80250039}, Month = {7}, Nlm_Id = {0406041}, Number = {2}, Pages = {333-59}, Pubmed = {7400401}, Title = {Degeneration of hippocampal CA3 pyramidal cells induced by intraventricular kainic acid}, Uuid = {D1E9F199-FFC4-48AD-BBBA-345DA517E55B}, Volume = {192}, Year = {1980}} @article{Nagano:2004, Abstract = {In the developing neocortex, most excitatory neurons are supplied and arranged through radial migration. Because neurons show global morphological changes and complicated behavior during that migration, precise regulation of cell shape and polarity is essential for proper migration and correct neocortical formation; however, how cell shape and polarity are regulated in migrating neuron remains elusive. We show here that Filamin A, a well known actin-binding protein, determines the shape of neocortical neurons during radial migration in vivo. Dysfunction of Filamin A, caused by a mutant Filamin A expression, prevents cells from acquiring consistent polarity toward specific direction and decreases motility in the subventricular and intermediate zones. In contrast, Filamin A overexpression, achieved by a short interfering RNA for Filamin A-interacting protein that induces Filamin A degradation (FILIP), promotes the development and maintenance of a bipolar shape also in the subventricular and intermediate zones. These results suggest that the amount of Filamin A helps migrating neurons determine their mode of migration, multipolar or bipolar, before entering the cortical plate and that FILIP is responsible, at least in part, for Filamin A content. In addition, our results also give a possible clue to understanding the pathogenesis of human malformation periventricular heterotopia, which is caused by various "loss-of-function" mutations in the filamin A gene.}, Author = {Nagano, Takashi and Morikubo, Soichi and Sato, Makoto}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Pregnancy;Animals;Tissue Culture Techniques;Carrier Proteins;Rats;Transfection;Microfilament Proteins;21 Epilepsy;Neocortex;Female;Cell Movement;Cell Polarity;RNA Interference;Mice, Inbred C57BL;Rats, Wistar;Gene Transfer Techniques;21 Neurophysiology;Mice;24 Pubmed search results 2008;Contractile Proteins;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {8102140}, Number = {43}, Organization = {Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, Matsuoka, Fukui 910-1193, Japan.}, Pages = {9648-57}, Pii = {24/43/9648}, Pubmed = {15509752}, Title = {Filamin A and FILIP (Filamin A-Interacting Protein) regulate cell polarity and motility in neocortical subventricular and intermediate zones during radial migration}, Uuid = {05245B5A-B74D-444A-9DD3-CA16452CB3D9}, Volume = {24}, Year = {2004}, url = {papers/Nagano_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2363-04.2004}} @article{Nagano:2002, Abstract = {Precisely regulated radial migration out of the ventricular zone is essential for corticogenesis. Here, we identify a mechanism that can tether ventricular zone cells in situ. FILIP interacts with Filamin A, an indispensable actin-binding protein that is required for cell motility, and induces its degradation in COS-7 cells. Degradation of Filamin A is identified in the cortical ventricular zone, where filip mRNA is localized. Furthermore, most ventricular zone cells that overexpress FILIP fail to migrate in explants. These results demonstrate that FILIP functions through a Filamin A F-actin axis to control the start of neocortical cell migration from the ventricular zone.}, Author = {Nagano, Takashi and Yoneda, Takunari and Hatanaka, Yumiko and Kubota, Chikara and Murakami, Fujio and Sato, Makoto}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Carrier Proteins;Rats;Microfilament Proteins;21 Epilepsy;Neocortex;Cell Movement;COS Cells;Rats, Wistar;In Situ Hybridization;21 Neurophysiology;Cytoskeleton;Contractile Proteins;Molecular Sequence Data;Amino Acid Sequence;24 Pubmed search results 2008;Actins;Cytoskeletal Proteins}, Medline = {22100428}, Month = {7}, Nlm_Id = {100890575}, Number = {7}, Organization = {Department of Anatomy 2, Fukui Medical University, 23 Shimoaizuki, Matsuoka, Fukui 910-1193, Japan.}, Pages = {495-501}, Pii = {ncb808}, Pubmed = {12055638}, Title = {Filamin A-interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone}, Uuid = {AF740D8E-9E4C-432B-A525-13C70BF1CE81}, Volume = {4}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb808}} @article{Nagayama:2007, Abstract = {A central question about the brain is how information is processed by large populations of neurons embedded in intricate local networks. Answering this question requires not only monitoring functional dynamics of many neurons simultaneously, but also interpreting such activity patterns in the context of neuronal circuitry. Here, we introduce a versatile approach for loading Ca(2+) indicators in vivo by local electroporation. With this method, Ca(2+) imaging can be performed both at neuron population level and with exquisite subcellular resolution down to dendritic spines and axon boutons. This enabled mitral cell odor-evoked ensemble activity to be analyzed simultaneously with revealing their specific connectivity to different glomeruli. Colabeling of Purkinje cell dendrites and intersecting parallel fibers allowed Ca(2+) imaging of both presynaptic boutons and postsynaptic dendrites. This approach thus provides an unprecedented capability for in vivo visualizing active cell ensembles and tracing their underlying local neuronal circuits.}, Author = {Nagayama, Shin and Zeng, Shaoqun and Xiong, Wenhui and Fletcher, Max L. and Masurkar, Arjun V. and Davis, Douglas J. and Pieribone, Vincent A. and Chen, Wei R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Electric Stimulation;Animals;Evoked Potentials;Dextrans;Afferent Pathways;Brain;Diagnostic Imaging;Electroporation;Vibrissae;Calcium;research support, non-u.s. gov't;Odors;Dendrites;Nerve Net;21 Neurophysiology;Neurons;research support, n.i.h., extramural;Mice;optical physiology;optical imaging;Olfactory Bulb;Neocortex;Technique;Gene Transfer Techniques;calcium imaging;frontiers review}, Mid = {NIHMS19945}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Neurobiology, Yale University, New Haven, CT 06520-8001, USA.}, Pages = {789-803}, Pii = {S0896-6273(07)00138-9}, Pmc = {PMC1892750}, Pubmed = {17359915}, Title = {In vivo simultaneous tracing and Ca(2+) imaging of local neuronal circuits}, Uuid = {23E2426E-3E52-4992-B470-0F74BB393A93}, Volume = {53}, Year = {2007}, url = {papers/Nagayama_Neuron2007.pdf}, Bdsk-File-2 = {papers/Nagayama_Neuron2007a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.02.018}} @article{Nait-Oumesmar:2007, Abstract = {In multiple sclerosis (MS), oligodendrocyte and myelin destruction lead to demyelination with subsequent axonal loss. Experimental demyelination in rodents has highlighted the activation of the subventricular zone (SVZ) and the involvement of progenitor cells expressing the polysialylated form of neural cell adhesion molecule (PSA-NCAM) in the repair process. In this article, we studied the distribution of early PSA-NCAM(+) progenitors in the SVZ and MS lesions in human postmortem brains. Compared with controls, MS SVZ showed a 2- to 3-fold increase in cell density and proliferation, which correlated with enhanced numbers of PSA-NCAM(+) and glial fibrillary acidic protein-positive (GFAP(+)) cells. PSA-NCAM(+) progenitors mainly were Sox9(+), and a few expressed Sox10 and Olig2, markers of oligodendroglial specification. PSA-NCAM(+) progenitors expressing Sox10 and Olig2 also were detected in demyelinated MS lesions. In active and chronic active lesions, the number of PSA-NCAM(+) progenitors was 8-fold higher compared with chronic silent lesions, shadow plaques, and normal-appearing white matter. In active and chronic active lesions, PSA-NCAM(+) progenitors were more frequent in periventricular lesions (30-50\%) than in lesions remote from the ventricular wall. These data indicate that, as in rodents, activation of gliogenesis in the SVZ occurs in MS and suggest the mobilization of SVZ-derived early glial progenitors to periventricular lesions, where they could give rise to oligodendrocyte precursors. These early glial progenitors could be a potential target for therapeutic strategies designed to promote myelin repair in MS.}, Author = {Nait-Oumesmar, Brahim and Picard-Riera, Nathalie and Kerninon, Christophe and Decker, Laurence and Seilhean, Danielle and H{\"o}glinger, G{\"u}nter U. and Hirsch, Etienne C. and Reynolds, Richard and Baron-Van Evercooren, Anne}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {02 Adult neurogenesis migration;11 Glia;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7505876}, Number = {11}, Organization = {*Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, Unit{\'e} 546, 75013 Paris, France.}, Pages = {4694-9}, Pii = {0606835104}, Pubmed = {17360586}, Title = {Activation of the subventricular zone in multiple sclerosis: Evidence for early glial progenitors}, Uuid = {2B68AA16-D116-4214-B909-6EB87C57A877}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0606835104}} @article{Najm:2000, Abstract = {PURPOSE: Human cortical dysplasia (CD) is a frequent cause of medically intractable focal epilepsy. The neurotransmitter mechanisms of epileptogenicity in these lesions have been attributed to changes in various glutamate receptor subtypes. Increased N-methyl-D-aspartate (NMDA) receptor (NR) 2A/B coassembled with NR1 subunits has been shown in focal epileptic CD. The purpose of this study is to correlate in situ CD epileptogenicity and the expression of various glutamate receptor subtypes. METHODS: The histopathological, morphological, and immunocytochemical findings in cortical tissue resected from five patients with medically intractable epilepsy and CD were correlated with electroencephalographic data recorded from subdural grids. The NMDA antibodies identified subunits NR1 (splicing variants 1a, 1b, 2a, and 2b) and NR2A/B. RESULTS: Epileptogenic specimens displayed the following common features: (a) widespread histological abnormalities of horizontal and columnar dyslamination, neurons with inverted polarity, and more extensive dendritic changes; (b) significantly higher NR2A/B immunoreactivity in both the dysplastic somata and all their dendritic processes; and (c) no statistically significant change in NR1 subunit expression but a more pronounced staining of the apical dendrites in highly epileptogenic cortex. These abnormalities were either absent or minimal in resected specimens that did not show evidence of severe in vivo epileptogenicity. CONCLUSION: These studies provide direct evidence for a major contribution of the NR2A/B subunit in CD-induced epileptogenicity.}, Author = {Najm, I. M. and Ying, Z. and Babb, T. and Mohamed, A. and Hadam, J. and LaPresto, E. and Wyllie, E. and Kotagal, P. and Bingaman, W. and Foldvary, N. and Morris, H. and L{\"u}ders, H. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:53 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {10 Development;Magnetic Resonance Imaging;Epilepsies, Partial;Humans;Up-Regulation;Frontal Lobe;Female;Male;10 genetics malformation;research support, u.s. gov't, p.h.s.;Cerebral Cortex;Adult;Immunohistochemistry;Receptors, N-Methyl-D-Aspartate;24 Pubmed search results 2008;Electroencephalography;Electrodes, Implanted;Adolescent}, Month = {8}, Nlm_Id = {2983306R}, Number = {8}, Organization = {Department of Neurology, The Cleveland Clinic Foundation, Ohio 44195, USA. najmi\@ccf.org}, Pages = {971-6}, Pubmed = {10961623}, Title = {Epileptogenicity correlated with increased N-methyl-D-aspartate receptor subunit NR2A/B in human focal cortical dysplasia}, Uuid = {F89648E7-ED23-4A40-94B3-1973D743C9AA}, Volume = {41}, Year = {2000}, url = {papers/Najm_Epilepsia2000.pdf}} @article{Najm:2007, Abstract = {Cortical dysplasia (CD, also known as malformations of cortical development) are the pathological substrates in a large percentage of patients with pharmacoresistant epilepsy who may be amenable to surgical treatment. Therefore, research on the mechanisms of dysplastic lesion formation and epileptogenicity is of paramount importance for the prevention, detection, and treatment of CD-induced epilepsy. The purpose of this review is to discuss and critically evaluate the current state and results of human tissue experimentation (focusing on reported results of studies done on neocortical dysplastic tissue resected from patients with pharmacoresistant epilepsy), and to discuss some of the concerns related to research that uses surgically resected epileptic human tissue. The use of better animal models of CD as a tool toward the better understanding of the mechanisms of pathogenesis, epileptogenesis, and epileptogenicity of dysplastic lesions will be reviewed from the perspective of their usefulness in a model of translational research that should ultimately result in better diagnostic and therapeutic techniques of CD.}, Author = {Najm, Imad M. and Tilelli, Cristiane Q. and Oghlakian, Roger}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Epilepsy;Epilepsies, Partial;24 Pubmed search results 2008;21 Dysplasia-heterotopia;21 Neurophysiology;Terminology;Rats;Neocortex;Rats, Mutant Strains;Research;research support, n.i.h., extramural;Animals;Disease Models, Animal;Cerebral Cortex;review;Humans}, Nlm_Id = {2983306R}, Organization = {Cleveland Clinic Epilepsy Center Head, Section of Adult Epilepsy and Clinical Neurophysiology, 9500 Euclid Avenue, S51, Cleveland, OH 44195, USA. najmi\@ccf.org}, Pages = {21-32}, Pubmed = {17571350}, Title = {Pathophysiological mechanisms of focal cortical dysplasia: a critical review of human tissue studies and animal models}, Uuid = {04C28FEE-B87A-4FB2-90FB-232C4E2238DE}, Volume = {48 Suppl 2}, Year = {2007}} @article{Nakagawa:2000, Abstract = {PURPOSE: Mitogenic effects of seizures on granule cell progenitors in the dentate gyrus were studied in two rat models of epilepsy. We investigated which stage of epileptogenesis is critical for eliciting progenitor cell division and whether seizure-induced neuronal degeneration is responsible for the enhancement of progenitor cell division. METHODS: Seizures were induced by either kainic acid (KA) administration or electrical kindling. Neurogenesis of dentate granule cells was evaluated using the bromodeoxyuridine (BrdU) labeling method, and neuronal degeneration was assessed by in situ DNA fragmentation analysis. RESULTS: After injection of KA, the number of BrdU-positive granule cells began to increase at day 3 after the treatment, peaked at day 5, and returned to baseline at day 10. By day 13, the values were lower than control. After kindling, the number of BrdU-positive cells began to increase after five consecutive experiences of stage I seizures. The increase occurred from day 1 to day 3 after the last electrical stimulation, but returned to baseline by day 7. After generalized seizures were well established, repeated stimulation did not facilitate division of granule cell progenitors. DNA fragmentation was noted in pyramidal neurons in the CA1, CA3, and hilus regions at 18 h after KA injection, but not in the kindling model. CONCLUSIONS: These observations indicate that a mechanism in epileptogenesis boosts dentate progenitor cell division, but progenitor cells may become unreactive to prolonged generalized seizures. Pyramidal neuronal degeneration is not necessary for triggering the upregulation. It is suggested that newly born granule cells may play a role in the network reorganization that occurs during epileptogenesis.}, Author = {Nakagawa, E. and Aimi, Y. and Yasuhara, O. and Tooyama, I. and Shimada, M. and McGeer, P. L. and Kimura, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:57 -0400}, Journal = {Epilepsia}, Keywords = {Male;Dentate Gyrus/*pathology;Rats, Sprague-Dawley;Rats;Immunohistochemistry;D;Time Factors;Limbic System/*pathology;Animal;Seizures/*pathology;06 Adult neurogenesis injury induced;Support, Non-U.S. Gov't;Bromodeoxyuridine/diagnostic use;Disease Models, Animal;DNA Fragmentation;Stem Cells/*pathology}, Number = {1}, Organization = {Molecular Neuroscience Research Center, and Department of Pediatrics, Shiga University of Medical Science, Otsu, Japan. eijin\@interchange.ubc.ca}, Pages = {10-8.}, Title = {Enhancement of progenitor cell division in the dentate gyrus triggered by initial limbic seizures in rat models of epilepsy}, Uuid = {553ECD85-0FC4-49EC-BA3D-280D52B3A8EE}, Volume = {41}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10643917}} @article{Nakahira:2005, Abstract = {Neuronal migration defects in the hippocampus during development are thought to be involved in various mental disorders. Studies of neural cell migration in the developing cerebrum have focused mainly on the neocortex, but those that have been performed on the developing hippocampal formation have not been adequately carried out. In the present study, the morphological differentiation of immature neurons that form the laminar structure of the hippocampus was investigated by labeling ventricular surface cells with the expression vector of the enhanced-green-fluorescent-protein (EGFP) gene. Vector DNA was transfected into spatially and temporally restricted neuroepithelium of the hippocampal primordium by in utero electroporation, and the morphology of EGFP-labeled migratory neurons and their interrelationships with the radial glial arrangement were observed. Pyramidal cells of Ammon's horn began to migrate radially along glial processes from a broad area of neuroepithelium on embryonic day (E)14. Large numbers of multipolar cells were found in the intermediate zone in the initial stage and stratified pyramidal cells appeared later. Dentate granule cells were labeled later than (E)16 and originated from a restricted area of neuroepithelium adjacent to the fimbria. Their initial migration was rapid and independent of radial glial fibers. Subsequent tangential migration in the subpial space and their ultimate settling into the forming dentate gyrus were closely associated with the radial glia. These findings indicate that distinct cellular mechanisms are involved in the development of the cortical layer of Ammon's horn and dentate gyrus.}, Author = {Nakahira, Eiko and Yuasa, Shigeki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Research Support, Non-U.S. Gov't;10 Development;Cell Differentiation;Animals;10 Hippocampus;Pregnancy;Comparative Study;Female;Cell Count;Electroporation;Embryonic Development;Hippocampus;Green Fluorescent Proteins;Cell Movement;Male;Embryo;Mice, Inbred ICR;Gene Transfer Techniques;Neuroglia;Neurons;Age Factors;Mice;Immunohistochemistry;Uterus}, Month = {3}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Ultrastructural Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan. nakahira\@ncnp.go.jp}, Pages = {329-40}, Pubmed = {15682392}, Title = {Neuronal generation, migration, and differentiation in the mouse hippocampal primoridium as revealed by enhanced green fluorescent protein gene transfer by means of in utero electroporation}, Uuid = {7C9505F9-616E-4FD0-99DA-67F14FB0072D}, Volume = {483}, Year = {2005}, url = {papers/Nakahira_JCompNeurol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20441}} @article{Nakajima:1998, Abstract = {Although the physiological role of neurotrophins in neuronal development and survival has been extensively investigated, their role in glial cell physiology remains to be elucidated. In the present study, we investigated the effects of neurotrophins on cultured microglia from newborn rat brain. All of the neurotrophins tested nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), increased the secretion of plasminogen and urokinase type-plasminogen activator and specific activity of acid phosphatase, but suppressed the release of constitutively-produced and lipopolysaccharide-stimulated nitric oxide (NO) from microglia. The reverse transcription-polymerase chain reaction, immunocytochemical staining, and Western blotting revealed that cultured microglia express Trk A, B, and C, and low-affinity NGF receptor, LNGFRp75. Neurotrophin was found to phosphorylate Trk A and B, and the neurotrophin-induced enhancement of plasminogen-secretion was suppressed by protein kinase inhibitor, K252a. Furthermore, neurotrophins caused an activation of transcription factor, NF-kappaB. These results indicate that the neurotrophin family regulate the function of microglia through Trk and/or LNGFRp75-mediated signal transduction.}, Author = {Nakajima, K. and Kikuchi, Y. and Ikoma, E. and Honda, S. and Ishikawa, M. and Liu, Y. and Kohsaka, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Animals;Cells, Cultured;Acid Phosphatase;Rats;Phosphorylation;NF-kappa B;5'-Nucleotidase;Brain-Derived Neurotrophic Factor;Microglia;Neurotrophin 3;Culture Media, Conditioned;RNA, Messenger;Nerve Growth Factors;Not relevant;11 Glia;Reverse Transcriptase Polymerase Chain Reaction;Blotting, Southern;Receptors, Nerve Growth Factor;Plasminogen;Animals, Newborn;Support, Non-U.S. Gov't;Blotting, Western;Receptor Protein-Tyrosine Kinases;Cell Division;Urinary Plasminogen Activator;Nitric Oxide}, Medline = {98446874}, Month = {11}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo, Japan.}, Pages = {272-89}, Pii = {10.1002/(SICI)1098-1136(199811)24:3<272::AID-GLIA2>3.0.CO;2-4}, Pubmed = {9775979}, Title = {Neurotrophins regulate the function of cultured microglia}, Uuid = {8E3E6573-3B7C-434E-9DCD-2C55BD3D6FA3}, Volume = {24}, Year = {1998}, url = {papers/Nakajima_Glia1998.pdf}} @article{Nakajima:2001, Abstract = {Because microglia have been suggested to produce neurotrophins, we tested this ability in vitro. Rat primary microglia were found to constitutively secrete a limited amount of brain-derived neurotrophic factor (BDNF), but nerve growth factor (NGF) and neurotrophin-3 (NT-3) were undetectable in the conditioned medium. Stimulation of the cells with lipopolysaccharide (LPS) increased BDNF secretion, and induced NGF secretion. As a first step to examine this regulation system, the association of protein kinase C (PKC) was pharmacologically analyzed. A PKC activator, phorbol-12-myristate-13-acetate, enhanced the secretion of BDNF. Pre-treatment of microglia with a PKC inhibitor, bisindolylmaleimide, suppressed LPS-stimulated BDNF secretion as well as the constitutive one. These results suggest that the PKC signaling cascade is closely associated with BDNF secretion. Among PKC isoforms, PKCalpha probably plays a role in BDNF secretion, based on the results of experiments using a specific PKC activator, 1-oleoyl-2-acetyl-sn-glycerol, and a specific PKC inhibitor, G{\"o} 6976, and by immunoblotting. Taken together, these findings suggest that the secretion of BDNF from microglia is regulated through PKCalpha-associated signal transduction mechanism.}, Author = {Nakajima, K. and Honda, S. and Tohyama, Y. and Imai, Y. and Kohsaka, S. and Kurihara, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Protein Kinase C;Animals;Cells, Cultured;Nerve Growth Factor;Rats;Enzyme Inhibitors;Diglycerides;Brain-Derived Neurotrophic Factor;Microglia;Neurotrophin 3;Maleimides;Lipopolysaccharides;Culture Media, Conditioned;Nerve Growth Factors;Indoles;Not relevant;11 Glia;Antibodies;Support, Non-U.S. Gov't;Carcinogens;Tetradecanoylphorbol Acetate;Cerebral Cortex;Carbazoles;Isoenzymes}, Medline = {21385486}, Month = {8}, Nlm_Id = {7600111}, Number = {4}, Organization = {Institute of Life Science, Soka University, 1-236, Tangi-machi, Hachioji, Tokyo 192-8577. nakajima\@t.soka.ac.jp}, Pages = {322-31}, Pubmed = {11494368}, Title = {Neurotrophin secretion from cultured microglia}, Uuid = {3F07A720-6995-4C85-BFD3-BD6E35454D22}, Volume = {65}, Year = {2001}} @article{Nakamichi:2005, Abstract = {During neurotropic virus infection, microglia act as a source of chemokines, thereby regulating the recruitment of peripheral leukocytes and the multicellular immune response within the CNS. Herein, we present a comprehensive study on the chemokine production by microglia in response to double-stranded RNA (dsRNA), a conserved molecular pattern of virus infection. Transcriptional analyses of chemokine genes revealed that dsRNA strongly induces the expression of CXC chemokine ligand 10 (CXCL10) and CC chemokine ligand 5 (CCL5) in microglia. We also observed that the dsRNA stimulation triggered the activation of signaling pathways mediated by nuclear factor kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK), including extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK). The microglial CXCL10 response to dsRNA was induced via NF-kappaB, p38, and JNK pathways, whereas the dsRNA-induced CCL5 production was dependent on JNK, but not on the other signal-transducing molecules tested. In addition, the acidic environment of intracellular vesicles was required for the activation of cellular signaling in response to dsRNA. Taken together, these results suggest that the recognition of dsRNA structure selectively induces the CXCL10 and CCL5 responses in microglia through vacuolar pH-dependent activation of NF-kappaB and MAPK signaling pathways.}, Author = {Nakamichi, and Saiki, and Sawada, and Yamamuro, and Morimoto, and Kurane,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {07 Excitotoxicity Apoptosis;11 Glia;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {2985190R}, Organization = {Department of Virology 1, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan.}, Pii = {JNC3354}, Pubmed = {16086695}, Title = {Double-stranded RNA stimulates chemokine expression in microglia through vacuolar pH-dependent activation of intracellular signaling pathways}, Uuid = {94FA5E83-9FA5-417B-A70E-8E5F542DB6E2}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1471-4159.2005.03354.x}} @article{Nakamura:1998, Abstract = {To study the role of medial frontal cortex in learning and memory of sequential procedures, we examined neuronal activity of the presupplementary motor area (pre-SMA) and supplementary motor area (SMA) while monkeys (n = 2) performed a sequential button press task, "2 x 5 task." In this paradigm, 2 of 16 (4 x 4 matrix) light-emitting diode buttons (called "set") were illuminated simultaneously and the monkey had to press them in a predetermined order. A total of five sets (called "hyperset") was presented in a fixed order for completion of a trial. We examined the neuronal activity of each cell using two kinds of hypersets: new hypersets that the monkey experienced for the first time for which he had to find the correct orders of button presses by trial-and-error and learned hypersets that the monkey had learned with extensive practice (n = 16 and 10 for each monkey). To investigate whether cells in medial frontal cortex are involved in the acquisition of new sequences or execution of well-learned procedures, we examined three to five new hypersets and three to five learned hypersets for each cell. Among 345 task-related cells, we found 78 cells that were more active during performance of new hypersets than learned hypersets (new-preferring cells) and 18 cells that were more active for learned hypersets (learned-preferring cells). Among new-preferring cells, 33 cells showed a learning-dependent decrease of cell activity: their activity was highest at the beginning of learning and decreased as the animal acquired the correct response for each set with increasing reliability. In contrast, 11 learned-preferring cells showed a learning-dependent increase of neuronal activity. We found a difference in the anatomic distribution of new-preferring cells. The proportion of new-preferring cells was greater in the rostral part of the medial frontal cortex, corresponding to the pre-SMA, than the posterior part, the SMA. There was some trend that learned-preferring cells were more abundant in the SMA. These results suggest that the pre-SMA, rather than SMA, is more involved in the acquisition of new sequential procedures.}, Author = {Nakamura, K. and Sakai, K. and Hikosaka, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Electric Stimulation;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Eye Movements;Memory;Learning;Animals;Macaca;Male;Neurons;Frontal Lobe}, Medline = {99036906}, Month = {11}, Nlm_Id = {0375404}, Number = {5}, Organization = {Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan.}, Pages = {2671-87}, Pubmed = {9819272}, Title = {Neuronal activity in medial frontal cortex during learning of sequential procedures}, Uuid = {687CA804-948B-498F-BC21-66534FA0BA4C}, Volume = {80}, Year = {1998}} @article{Nakano:2001, Abstract = {BACKGROUND: Bone marrow transplantation is reportedly effective in preventing the progression of neurological deterioration in lysosomal storage disorders, although the mechanism underlying the therapeutic effects remains to be elucidated. Recent research on stem cell biology suggests that bone marrow cells contain nonhematopoietic stem cells, including brain precursor cells. To evaluate the contribution of bone marrow cells as carriers for cell and gene therapy of neurological disorders, we studied the fate of transplanted bone marrow cells in the adult mouse brain. METHODS: Bone marrow cells were genetically marked with a retroviral vector containing the green fluorescence protein gene and then transplanted into irradiated mice by either systemic infusion or direct injection. To identify cell types, brain sections were stained with specific antibodies against neuronal cell markers-neuron specific enolase for neurons, glial fibrillary acidic protein (GFAP) for astrocytes, carbonic anhydrase II (CAII) for oligodendrocytes, and ionized calcium binding adaptor molecule 1 (Iba1) for microglia-and then examined under a confocal microscope. RESULTS: Twenty-four weeks after systemic infusion, transplanted cells expressed Iba1 but none of the other brain cell markers. Conversely, 12 weeks after direct injection, transplanted cells were stained with antibodies against GFAP, CAII, and Iba1. CONCLUSIONS: Bone marrow contains cells capable of differentiating into oligodendrocytes, astrocytes, and microglia when exposed to the brain microenvironment. Autologous bone marrow cells may be useful as carriers for ex vivo gene therapy for lysosomal disorders with neurological symptoms.}, Author = {Nakano, K. and Migita, M. and Mochizuki, H. and Shimada, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0041-1337}, Journal = {Transplantation}, Keywords = {Cell Differentiation;Transduction, Genetic;Animals;Stereotaxic Techniques;Corpus Striatum;Bone Marrow Transplantation;Brain;Indicators and Reagents;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Bone Marrow Cells;Neuroglia;Mice;Injections, Intravenous;Luminescent Proteins;Injections;Research Support, Non-U.S. Gov't}, Medline = {21348760}, Month = {6}, Nlm_Id = {0132144}, Number = {12}, Organization = {Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.}, Pages = {1735-40}, Pubmed = {11455251}, Title = {Differentiation of transplanted bone marrow cells in the adult mouse brain}, Uuid = {847107A0-7F61-4EC6-BD71-7B4EF3477D37}, Volume = {71}, Year = {2001}} @article{Nakatomi:2002, Abstract = {The adult brain is extremely vulnerable to various insults. The recent discovery of neural progenitors in adult mammals, however, raises the possibility of repairing damaged tissue by recruiting their latent regenerative potential. Here we show that activation of endogenous progenitors leads to massive regeneration of hippocampal pyramidal neurons after ischemic brain injury. Endogenous progenitors proliferate in response to ischemia and subsequently migrate into the hippocampus to regenerate new neurons. Intraventricular infusion of growth factors markedly augments these responses, thereby increasing the number of newborn neurons. Our studies suggest that regenerated neurons are integrated into the existing brain circuitry and contribute to ameliorating neurological deficits. These results expand the possibility of novel neuronal cell regeneration therapies for stroke and other neurological diseases. 22190657 0092-8674 Journal Article}, Author = {Nakatomi, H. and Kuriu, T. and Okabe, S. and Yamamoto, S. and Hatano, O. and Kawahara, N. and Tamura, A. and Kirino, T. and Nakafuku, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Cell}, Keywords = {D}, Number = {4}, Organization = {Department of Neurobiology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan}, Pages = {429}, Title = {Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors}, Uuid = {BAA16E92-C26D-11DA-969D-000D9346EC2A}, Volume = {110}, Year = {2002}, url = {papers/Nakatomi_Cell2002.pdf}} @article{Naldini:1996, Abstract = {We describe the construction of a safe, replication-defective and efficient lentiviral vector suitable for in vivo gene delivery. The reverse transcription of the vector was found to be a rate-limiting step; therefore, promoting the reaction inside the vector particles before delivery significantly enhanced the efficiency of gene transfer. After injection into the brain of adult rats, sustained long-term expression of the transgene was obtained in the absence of detectable pathology. A high proportion of the neurons in the areas surrounding the injection sites of the vector expressed the transduced beta-galactosidase gene. This pattern was invariant in animals sacrificed several months after a single administration of the vector. Transduction occurs by integration of the vector genome, as it was abolished by a single amino acid substitution in the catalytic site of the integrase protein incorporated in the vector. Development of clinically acceptable derivatives of the lentiviral vector may thus enable the sustained delivery of significant amounts of a therapeutic gene product in a wide variety of somatic tissues.}, Author = {Naldini, L. and Bl{\"o}mer, U. and Gage, F. H. and Trono, D. and Verma, I. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {beta-Galactosidase;Animals;Kidney;Cytomegalovirus;Rats;Humans;research support, u.s. gov't, p.h.s. ;Lentivirus;Safety;15 Retrovirus mechanism;Animals, Genetically Modified;Genes, gag;Brain;Genes, pol;Genetic Vectors;research support, non-u.s. gov't ;Cell Line;Gene Transfer Techniques;Neurons;Lac Operon;Virus Integration;Genes, Reporter}, Month = {10}, Nlm_Id = {7505876}, Number = {21}, Organization = {Salk Institute for Biological Studies, San Diego, CA 92186-5800, USA.}, Pages = {11382-8}, Pubmed = {8876144}, Title = {Efficient transfer, integration, and sustained long-term expression of the transgene in adult rat brains injected with a lentiviral vector}, Uuid = {39E6E80D-45DB-4D22-A1D7-FBD0535676E1}, Volume = {93}, Year = {1996}, url = {papers/Naldini_ProcNatlAcadSciUSA1996.pdf}} @article{Nam:2007, Abstract = {Neuroblasts migrate long distances in the postnatal subventricular zone (SVZ) and rostral migratory stream (RMS) to the olfactory bulbs. Many fundamental features of SVZ migration are still poorly understood, and we addressed several important questions using two-photon time-lapse microscopy of brain slices from postnatal and adult eGFP(+) transgenic mice. 1) Longitudinal arrays of neuroblasts, so-called chain migration, have never been dynamically visualized in situ. We found that neuroblasts expressing doublecortin-eGFP (Dcx-eGFP) and glutamic acid decarboxylase-eGFP (Gad-eGFP) remained within arrays, which maintained their shape for many hours, despite the fact that there was a wide variety of movement within arrays. 2) In the dorsal SVZ, neuroblasts migrated rostrocaudally as expected, but migration shifted to dorsoventral orientations throughout ventral regions of the lateral ventricle. 3) Whereas polarized bipolar morphology has been a gold standard for inferring migration in histologic sections, our data indicated that migratory morphology was not predictive of motility. 4) Is there local motility in addition to long distance migration? 5) How fast is SVZ migration? Unexpectedly, one-third of motile neuroblasts moved locally in complex exploratory patterns and at average speeds slower than long distance movement. 6) Finally, we tested, and disproved, the hypothesis that all motile cells in the SVZ express doublecortin, indicating that Dcx is not required for migration of all SVZ cell types. These data show that cell motility in the SVZ and RMS is far more complex then previously thought and involves multiple cell types, behaviors, speeds, and directions. J. Comp. Neurol. 505:190-208, 2007. (c) 2007 Wiley-Liss, Inc.}, Author = {Nam, Sang Chae and Kim, Yongsoo and Dryanovski, Dilyan and Walker, Avery and Goings, Gwendolyn and Woolfrey, Kevin and Kang, Seong Su and Chu, Chris and Chenn, Anjen and Erdelyi, Ferenc and Szabo, Gabor and Hockberger, Philip and Szele, Francis G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {0406041}, Number = {2}, Organization = {Chonnam National University Medical School, Gwangju, Republic of Korea 501-746.}, Pages = {190-208}, Pubmed = {17853439}, Title = {Dynamic features of postnatal subventricular zone cell motility: A two-photon time-lapse study}, Uuid = {26B91A4C-3096-401B-BFA3-2F731D5B6E2C}, Volume = {505}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21473}} @article{Namba:2005, Abstract = {In the dentate gyrus neurons continue to be generated from late embryonic to adult stage. Recent extensive studies have unveiled several key aspects of the adult neurogenesis, but only few attempts have so far been made on the analysis of the early postnatal neurogenenesis, a transition state between the embryonic and adult neurogenesis. Here, we focus on the early postnatal neurogenesis and examine the nature and development of neural progenitor cells in Wistar rats. Immunohistochemistry for Ki67, a cell cycle marker, and 5-bromo-2-deoxyuridine (BrdU) labelling show that cell proliferation occurs mainly in the hilus and partly in the subgranular zone. A majority of the proliferating cells express S100beta and astrocyte-specific glutamate transporter (GLAST) and the subpopulation are also positive for glial fibrillary acidic protein (GFAP) and nestin. Tracing with BrdU and our modified retrovirus vector carrying enhanced green fluorescent protein (GFP) indicate that a substantial population of the proliferating cells differentiate into proliferative neuroblasts and immature neurons in the hilus, which then migrate to the granule cell layer (66.8\%), leaving a long axon-like process behind in the hilus, and the others mainly become star-shaped astrocytes (12.0\%) and radial glia-like cells (4.7\%) in the subgranular zone. These results suggest that the progenitors of the granule cells expressing astrocytic and radial glial markers, proliferate and differentiate into neurons mainly in the hilus during the early postnatal period.}, Author = {Namba, Takashi and Mochizuki, Hideki and Onodera, Masafumi and Mizuno, Yoshikuni and Namiki, Hideo and Seki, Tatsunori}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;10 Development;10 Hippocampus;Animals;Gene Expression Regulation, Developmental;Rats;Fluorescent Antibody Technique;Comparative Study;Hu Paraneoplastic Encephalomyelitis Antigens;Ki-67 Antigen;Zidovudine;Models, Biological;Cell Count;Rats, Wistar;Green Fluorescent Proteins;Cell Proliferation;Nerve Growth Factors;Animals, Newborn;Excitatory Amino Acid Transporter 1;Neuroglia;Intermediate Filament Proteins;Neurons;Age Factors;Dentate Gyrus;Stem Cells;Nerve Tissue Proteins;S100 Proteins;Glial Fibrillary Acidic Protein}, Month = {10}, Nlm_Id = {8918110}, Number = {8}, Organization = {Department of Anatomy, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo, Tokyo 113-8421, Japan.}, Pages = {1928-41}, Pii = {EJN4396}, Pubmed = {16262632}, Title = {The fate of neural progenitor cells expressing astrocytic and radial glial markers in the postnatal rat dentate gyrus}, Uuid = {1C9A8DB4-1B79-411B-A11A-F82D52C6E8D5}, Volume = {22}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2005.04396.x}} @article{Nanmoku:2003, Abstract = {Moloney murine leukemia retroviral vectors are more suitable as tools for gene delivery in vivo in comparison to other vectors due to their stable expression and absence of cytotoxicity. However, because of their low titers and poor proliferation rate in the adult nervous system, the application of retroviral vectors to the nervous system has been limited. To overcome this disadvantage, we have attempted to achieve higher viral titers and apply them to the embryonic mouse brain. By utilizing our improved packaging cell line and concentrating the viral supernatant by the low-speed centrifugation method, we have successfully increased the retroviral titer up to 10(12) cfu/ml. This titer is over 10(6)-fold greater than routinely achieved retroviral titers, and is comparable to, or even higher than, those of adenoviral vectors. We investigated the efficacy of gene transfer into the nervous system, which has thus far proven quite recalcitrant to genetic transfer by characteristically low retroviral titers. Using our retroviral preparation, we have demonstrated the highly efficient delivery and long-term expression of a foreign gene into neural cells both in vitro and in vivo. Moreover, we demonstrated that predominant gene delivery into the neurons of one cortical layer can be achieved by choosing an appropriate date of retroviral infection. 0378-5866 Journal Article}, Author = {Nanmoku, K. and Kawano, M. and Iwasaki, Y. and Ikenaka, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Dev Neurosci}, Keywords = {Transduction, Genetic/*methods;15 Retrovirus mechanism;Embryo;J pdf;Animals, Newborn;Brain/*physiology;Neurons/physiology;Female;Moloney murine leukemia virus/*genetics;Pregnancy;3T3 Cells;Injections, Intraventricular;Fibroblasts/physiology;Support, Non-U.S. Gov't;Animals;Mice;Genetic Vectors/administration &dosage}, Number = {2-4}, Organization = {Laboratory of Neural Information, National Institute for Physiological Sciences, Okazaki, Aichi, Japan.}, Pages = {152-61}, Pubmed = {12966213}, Title = {Highly efficient gene transduction into the brain using high-titer retroviral vectors}, Uuid = {B5B6E11E-5A03-4F90-AD60-F2BDCB30B56D}, Volume = {25}, Year = {2003}, url = {papers/Nanmoku_DevNeurosci2003.pdf}} @article{Narasimhan:2005, Author = {Narasimhan, Kalyani}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Brain Injuries;Adenosine Triphosphate;Brain Diseases;Phagocytosis;Signal Transduction;Gliosis;11 Glia;Microglia;comment;Mice;Animals;Humans;Receptors, Purinergic P2;news}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Pages = {707}, Pii = {nn0605-707}, Pubmed = {15917834}, Title = {Brain's guard cells show their agility}, Uuid = {3DA0C994-99E2-4621-9787-56001C0D7E05}, Volume = {8}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0605-707}} @article{Nataf:2001, Abstract = {Expression of the C5a receptor in the central nervous system has been demonstrated on microglia, astrocytes and neurons. In the present study, we demonstrate C5aR expression in vitro by rat and murine O2-A progenitor cells and oligodendrocytes. We also observed that in vitro differentiation of O2-A progenitors into mature oligodendrocytes is accompanied by down-regulation of C5aR mRNA expression. These results suggest that the C5aR may be a marker for oligodendroglial differentiation and play a role in oligodendrocyte function. 21149821 0006-8993 Journal Article}, Author = {Nataf, S. and Levison, S. W. and Barnum, S. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Brain Res}, Keywords = {In Situ Hybridization;Flow Cytometry;Stem Cells/cytology/physiology;G abstr;Gene Expression/physiology;Rats;Cell Differentiation/physiology;Cell Lineage/physiology;RNA, Messenger/analysis;11 Glia;Animal;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Cells, Cultured;Oligodendroglia/cytology/*physiology;Receptors, Complement/*genetics;Antigens, CD/*genetics}, Number = {2}, Organization = {Department of Microbiology, University of Alabama at Birmingham, 35294, USA.}, Pages = {321-6}, Pubmed = {11251209}, Title = {Expression of the anaphylatoxin C5a receptor in the oligodendrocyte lineage}, Uuid = {94F762E2-99FE-4D18-8D59-2A5102D77165}, Volume = {894}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11251209}} @article{Nath:2000, Abstract = {Unilateral injection of 50 nmol of N-methyl-D-aspartate (NMDA) into the left posterior striatum of 7 day-old rat pups induces massive neuronal loss in the ipsilateral hemisphere in 5 days. In this model of excitotoxicity, the form of neuronal death (necrosis vs apoptosis) has not been clearly addressed. Here we report evidence of DNA laddering in the ipsilateral hemisphere 24 h after the NMDA injection. Activation of apoptosis-linked caspase(s) was also identified, as evidenced by (i) the formation of caspase-produced 120 kDa alpha-spectrin breakdown product (SBDP120) and (ii) increase in hydrolysis of caspase-3 substrate acetyl-DEVD-7-amido-4-methylcoumarin in the homogenate from the ipsilateral hemisphere. Lastly, we note that i.p. injection (100 mg/kg) of a pan caspase inhibitor Z-D-DCB attenuates the levels of SBDP120. Our results suggest the presence of caspase-activation in this rat pup model of NMDA toxicity.}, Author = {Nath, R. and Scott, M. and Nadimpalli, R. and Gupta, R. and Wang, K. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Neurochem Int}, Keywords = {Enzyme Inhibitors/pharmacology;Enzyme Activation;Rats, Sprague-Dawley;07 Excitotoxicity Apoptosis;Caspases/antagonists &inhibitors/*metabolism;Rats;Brain/enzymology/metabolism;E-14;*Apoptosis;Brain Diseases/*chemically induced/*enzymology/metabolism;Animal;Spectrin/metabolism;*N-Methylaspartate;*Animals, Newborn;DNA Fragmentation;In Situ Nick-End Labeling}, Number = {2}, Organization = {Department of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Division of'Warner-Lambert Company, Ann Arbor, Michigan, 48105, USA. rathna.nath\@wl.com}, Pages = {119-26.}, Title = {Activation of apoptosis-linked caspase(s) in NMDA-injured brains in neonatal rats}, Uuid = {F94582C9-7431-41CF-A752-A6786551EAB3}, Volume = {36}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10676875}} @article{Nathan:2001, Abstract = {Apolipoprotein E (apoE), a lipid transporting protein, has been postulated to participate in nerve regeneration. To better clarify apoE function in the olfactory system, we evaluated the amount and distribution of apoE in the olfactory bulb following olfactory nerve lesion in mice. Olfactory nerve was lesioned in 2- to 4-month-old mice by intranasal irrigation with Triton X-100. Olfactory bulbs were collected at 0, 3, 7, 21, 42, and 56 days postlesion, and both apoE concentrations and apoE distribution were determined. ApoE levels, as determined by immunoblot analysis, were twofold greater than normal during nerve degeneration at 3 days. ApoE levels remained elevated by approximately 1.5 times normal levels at 7 through 21 days after injury and returned to baseline by 56 days. Immunocytochemical studies supported these observations. ApoE immunoreactivity was prominent on the olfactory nerve at 3 days after lesion and decreased to baseline levels at later time periods. Double-labeling immunocytochemical studies confirmed that both reactive astroglia and microglia produced detectable amounts of apoE following the lesion. Return of apoE expression to baseline paralleled measures of olfactory nerve maturation as measured by olfactory marker protein. These data suggest that apoE increases concurrent with nerve degeneration. ApoE may facilitate efficient regeneration perhaps by recycling lipids from degenerating fibers for use by growing axons. The association of apoE genotype with dementing illnesses may represent a diminished ability to support a lifetime of nerve regeneration. Copyright 2001 Academic Press.}, Author = {Nathan, B. P. and Nisar, R. and Randall, S. and Short, J. and Sherrow, M. and Wong, G. K. and Struble, R. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Exp Neurol}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {1}, Organization = {Department of Biological Sciences, Eastern Illinois University, 600 Lincoln Avenue, Charleston, Illinois, 61920}, Pages = {128-36.}, Title = {Apolipoprotein e is upregulated in olfactory bulb glia following peripheral receptor lesion in mice}, Uuid = {4A26FBA8-342B-4A3B-9779-57766212D424}, Volume = {172}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11681846}} @article{Naundorf:2006, Abstract = {Neurons process and encode information by generating sequences of action potentials. For all spiking neurons, the encoding of single-neuron computations into sequences of spikes is biophysically determined by the cell's action-potential-generating mechanism. It has recently been discovered that apparently minor modifications of this mechanism can qualitatively change the nature of neuronal encoding. Here we quantitatively analyse the dynamics of action potential initiation in cortical neurons in vivo, in vitro and in computational models. Unexpectedly, key features of the initiation dynamics of cortical neuron action potentials--their rapid initiation and variable onset potential--are outside the range of behaviours described by the classical Hodgkin-Huxley theory. We propose a new model based on the cooperative activation of sodium channels that reproduces the observed dynamics of action potential initiation. This new model predicts that Hodgkin-Huxley-type dynamics of action potential initiation can be induced by artificially decreasing the effective density of sodium channels. In vitro experiments confirm this prediction, supporting the hypothesis that cooperative sodium channel activation underlies the dynamics of action potential initiation in cortical neurons.}, Author = {Naundorf, Bj{\"o}rn and Wolf, Fred and Volgushev, Maxim}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {0410462}, Number = {7087}, Organization = {Max Planck Institute for Dynamics and Self-Organization, University of G{\"o}ttingen, Bunsenstr. 10, D-37073 G{\"o}ttingen, Germany.}, Pages = {1060-3}, Pii = {nature04610}, Pubmed = {16625198}, Title = {Unique features of action potential initiation in cortical neurons}, Uuid = {88A6FC17-8012-4760-917C-4362E60202D8}, Volume = {440}, Year = {2006}, url = {papers/Naundorf_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04610}} @article{Nacher:2007, Abstract = {N-methyl-d-aspartate (NMDA) receptors play a crucial role in the regulation of neuronal development during embryogenesis and they also regulate the rate of neurogenesis and proliferation in the adult dentate gyrus. However, the mechanism by which they influence these processes is not fully understood. NMDA receptors seem to be functional in hippocampal precursor cells and recently generated granule neurons, although there is no anatomical correlate of these physiological observations. We have analyzed the expression of the NMDA receptor subunits NR1 and NR2B in precursor cells and recently generated granule neurons of the adult rat dentate gyrus, using 5'bromodeoxyuridine, green fluorescent protein-retrovirus and immunohistochemistry. Our results indicate that NR1 and NR2B are expressed in some proliferating cells of the adult subgranular zone. These receptors are absent from transiently amplifying progenitors (type 2-3 cells) but they are found in glial fibrillar acidic protein expressing cells in the subgranular zone, suggesting its presence in bipotential (type-1) precursor cells. NR1 and NR2B are rarely found in granule cells younger than 60 h. By contrast, many granule cells generated 14 days before killing express both NMDA receptor subunits. These results demonstrate that adult hippocampal neurogenesis may be regulated by NMDA receptors present in precursor cells and in differentiating granule neurons, although these receptors are probably not located on synapses. However, an indirect effect through NMDA receptors located in other cell types should not be excluded.}, Author = {N{\'a}cher, J. and Varea, E. and Miguel Blasco-Ib{\'a}\~{n}ez, J. and Go{\'o}mez-Climent, M. A. and Castillo-G{\'o}mez, E. and Crespo, C. and Mart{\'\i}nez-Guijarro, F. J. and McEwen, B. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {7605074}, Number = {3}, Organization = {Neurobiology Unit and Program in Basic and Applied Neurosciences, Cell Biology Department, Universitat de Val\`{e}ncia, Dr. Moliner, 50, Burjassot, 46100, Spain.}, Pages = {855-64}, Pii = {S0306-4522(06)01378-9}, Pubmed = {17157994}, Title = {N-methyl-d-aspartate receptor expression during adult neurogenesis in the rat dentate gyrus}, Uuid = {739AA9C5-8F22-441E-B48D-7A0213FB7EA9}, Volume = {144}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2006.10.021}} @article{Nedergaard:2003, Author = {Nedergaard, Maiken and Ransom, Bruce and Goldman, Steven A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Brain;Research Support, Non-U.S. Gov't;03 Adult neurogenesis progenitor source;Cell Communication;Astrocytes;Research Support, U.S. Gov't, P.H.S.;11 Glia;review, tutorial;Blood Vessels;Calcium Signaling;Humans;Animals;Endothelial Cells;review;Neurons}, Medline = {22886085}, Month = {10}, Nlm_Id = {7808616}, Number = {10}, Organization = {Department of Cell Biology, New York Medical College, Valhalla, NY 10595, USA. maiken\_nedergaard\@nymc.edu}, Pages = {523-30}, Pii = {S0166223603002662}, Pubmed = {14522144}, Title = {New roles for astrocytes: redefining the functional architecture of the brain}, Uuid = {17E82B9C-F656-40A4-8FB5-0E1AB60BA762}, Volume = {26}, Year = {2003}} @article{Nedivi:1998, Abstract = {Activity-independent and activity-dependent mechanisms work in concert to regulate neuronal growth, ensuring the formation of accurate synaptic connections. CPG15, a protein regulated by synaptic activity, functions as a cell-surface growth-promoting molecule in vivo. In Xenopus laevis, CPG15 enhanced dendritic arbor growth in projection neurons, with no effect on interneurons. CPG15 controlled growth of neighboring neurons through an intercellular signaling mechanism that requires its glycosylphosphatidylinositol link. CPG15 may represent a new class of activity-regulated, membrane-bound, growth-promoting proteins that permit exquisite spatial and temporal control of neuronal structure.}, Author = {Nedivi, E. and Wu, G. Y. and Cline, H. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Signal Transduction;Animals;Image Processing, Computer-Assisted;Neuronal Plasticity;Microscopy, Confocal;Recombinant Proteins;research support, non-u.s. gov't;Genetic Vectors;Dendrites;Xenopus laevis;Superior Colliculus;21 Neurophysiology;Vaccinia virus;research support, u.s. gov't, p.h.s.;Neurons;Interneurons;24 Pubmed search results 2008;Membrane Proteins;Nerve Tissue Proteins;Glycosylphosphatidylinositols;Ligands}, Month = {9}, Nlm_Id = {0404511}, Number = {5384}, Organization = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA. nedivi\@cshl.org}, Pages = {1863-6}, Pubmed = {9743502}, Title = {Promotion of dendritic growth by CPG15, an activity-induced signaling molecule}, Uuid = {0E3393CA-3F59-4980-83D5-37B60631ABD1}, Volume = {281}, Year = {1998}} @article{Negishi:2003, Abstract = {We established selective primary cultures of neurons, astrocytes, and microglial cells from cryopreserved fetal cerebral cortex of cynomolgus monkeys (Macaca fascicularis). At 14 days in serum-containing medium, the cell cultures of the fetal cerebral cortex consisted primarily of neurons, astrocytes, and floating microglial cells. At 21 days, we observed a small number of myelin basic protein (MBP)-positive oligodendrocytes. The addition of cytosine arabinoside (a selective DNA synthesis inhibitor) at 2 days in culture eliminated proliferative glial cells, allowing adequate numbers of neurons to survive selectively. A chemically defined serum-free medium successfully supported neuronal survival at a level equivalent to that supported by the serum-containing medium. Brain-derived neurotrophic factor (BDNF) significantly affected the survival of primate neurons. Glutamate induced a significant degree of neuronal cell death against primate neurons and MK-801, a selective N-methyl-D-aspartate receptor (NMDAR) antagonist, blocked cell death, which suggests that primate cortical neurons have NMDAR and the glutamate-induced cell toxicity is mediated by NMDAR. In the serum-free medium, type-1 astrocytes responded to dibutyryl cyclic AMP and showed a process-bearing morphology. The growth of type-1 astrocytes in the serum-free medium was stimulated by epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and hydrocortisone, which are known growth factors in rat type-1 astrocytes. Cultured microglial cells expressed CD68, a monocyte marker. Macrophage-colony stimulating factor (M-CSF) stimulated microglial cell growth in the serum-free medium. These selective primary culture systems of primate cerebral cortical cells will be useful in issues involving species specificity in neuroscience.}, Author = {Negishi, Takayuki and Ishii, Yoshiyuki and Kyuwa, Shigeru and Kuroda, Yoichiro and Yoshikawa, Yasuhiro}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Fetus;Dose-Response Relationship, Drug;Excitatory Amino Acid Antagonists;Animals;Culture Media, Serum-Free;Antigens, Differentiation, Myelomonocytic;Astrocytes;Cells, Cultured;Glutamic Acid;Comparative Study;Myelin Basic Proteins;Dizocilpine Maleate;Microglia;Microtubule-Associated Proteins;Antigens, CD;Macaca fascicularis;11 Glia;Immunosuppressive Agents;Cytarabine;Cyclic CMP;Cerebral Cortex;Neurons;Epidermal Growth Factor;Fibroblast Growth Factors;Cell Division;Cell Culture;Immunohistochemistry;Cell Death;Glial Fibrillary Acidic Protein}, Month = {12}, Nlm_Id = {7905558}, Number = {1-2}, Organization = {Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. taka-u\@yayoi.club.ne.jp}, Pages = {133-40}, Pii = {S0165027003002681}, Pubmed = {14659833}, Title = {Primary culture of cortical neurons, type-1 astrocytes, and microglial cells from cynomolgus monkey (Macaca fascicularis) fetuses}, Uuid = {9CA6F93F-572B-4D60-BFCB-6AE05199CCE2}, Volume = {131}, Year = {2003}, url = {papers/Negishi_JNeurosciMethods2003.pdf}} @article{Nelson:2006, Abstract = {Distinct neuronal cell types acquire and maintain their identity by expressing different genes. Recently it has become feasible to measure this cell type specific expression by isolating and amplifying mRNA from small populations of fluorescently labeled neurons and probing this mRNA with microarrays. Prior to this, most neuronal gene expression studies used tissue homogenates or randomly selected single cells and were, therefore, not well suited to studying transcriptional differences between cell types. Microarray studies of purified cell types have enabled investigators to identify the transcriptional signatures of, for example, subtypes of pyramidal neurons and interneurons in the neocortex, modulatory dopaminergic and serotonergic neurons, and the striatal neurons that form the so-called 'direct' and 'indirect' pathways through the basal ganglia. These studies are opening up new approaches to understanding brain circuitry, plasticity and pathology and are refining the concept of the neuronal cell type.}, Author = {Nelson, Sacha B. and Hempel, Chris and Sugino, Ken}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {24 Pubmed search results 2008;21 Neurophysiology;Oligonucleotide Array Sequence Analysis;Gene Expression Profiling;Gene Expression;Transcription, Genetic;research support, n.i.h., extramural;Animals;Brain;Humans;review;Neurons}, Month = {10}, Nlm_Id = {9111376}, Number = {5}, Organization = {Department of Biology and National Center for Behavioral Genomics, Brandeis University, MS 008, 415 South Street, Waltham, Massachusetts 02454-9110, USA.}, Pages = {571-6}, Pii = {S0959-4388(06)00112-7}, Pubmed = {16962313}, Title = {Probing the transcriptome of neuronal cell types}, Uuid = {223EDF25-1CD1-45CC-8F65-ADC31D955650}, Volume = {16}, Year = {2006}, url = {papers/Nelson_CurrOpinNeurobiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2006.08.006}} @article{Nelson:2003, Abstract = {Cell polarity is defined as asymmetry in cell shape, protein distributions and cell functions. It is characteristic of single-cell organisms, including yeast and bacteria, and cells in tissues of multi-cell organisms such as epithelia in worms, flies and mammals. This diversity raises several questions: do different cell types use different mechanisms to generate polarity, how is polarity signalled, how do cells react to that signal, and how is structural polarity translated into specialized functions? Analysis of evolutionarily diverse cell types reveals that cell-surface landmarks adapt core pathways for cytoskeleton assembly and protein transport to generate cell polarity. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Nelson, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Nature}, Keywords = {Cell Size;10 Development;Protein Transport;Signal Transduction;Epithelial Cells/cytology/metabolism;*Cell Polarity;Mitosis;Animals;F pdf;Cytoskeleton/chemistry/*metabolism}, Number = {6933}, Organization = {Department of Molecular and Cellular Physiology, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, Stanford, California 94305-5435, USA. wjnelson\@stanford.edu}, Pages = {766-74}, Pubmed = {12700771}, Title = {Adaptation of core mechanisms to generate cell polarity}, Uuid = {C63B60CB-D85C-4C6C-96EA-238003972DD6}, Volume = {422}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12700771}} @article{Nelson:2006a, Abstract = {Neural circuits within the vertebrate brain are composed of highly diverse cell types. The exact extent of this diversity is a matter of continuing debate. For example, do cortical interneurons comprise a few, dozens or >100 distinct cell types? Recently, several groups have used microarrays to measure genome-wide gene expression profiles for specific neuronal cell types. These methods can offer an objective basis for neuronal classification. In this review, we argue that this approach should now be carried out more broadly and that it should be coupled to large-scale efforts to generate mouse driver lines in which tools for genetic manipulation, such as the Cre recombinase, are expressed in identified cell types within the brain. This would enable neuroscientists to begin to investigate more systematically the roles of specific genes in establishing particular cellular phenotypes, and also the roles of particular cell types within brain circuits. This review is part of the TINS special issue on The Neural Substrates of Cognition.}, Author = {Nelson, Sacha B. and Sugino, Ken and Hempel, Chris M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {review;24 Pubmed search results 2008;21 Neurophysiology;Gene Expression Profiling;Nerve Net;Humans;Animals;Genomics;Neurons;Brain}, Month = {6}, Nlm_Id = {7808616}, Number = {6}, Organization = {Department of Biology and National Center for Behavioral Genomics, Brandeis University, MS 008, 415 South Street, Waltham, MA 02454-9110, USA. nelson\@brandeis.edu}, Pages = {339-45}, Pii = {S0166-2236(06)00092-0}, Pubmed = {16714064}, Title = {The problem of neuronal cell types: a physiological genomics approach}, Uuid = {6AC60999-13D5-490A-96A8-41469EF677EA}, Volume = {29}, Year = {2006}, url = {papers/Nelson_TrendsNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2006.05.004}} @article{Nemet:2004, Abstract = {We present a method to optically measure and image the membrane potential of neurons, using the nonlinear optical phenomenon of second harmonic generation (SHG) with a photopigment retinal as the chromophore [second harmonic retinal imaging of membrane potential (SHRIMP)]. We show that all-trans retinal, when adsorbed to the plasma membrane of living cells, can report on the local electric field via its change in SHG. Using a scanning mode-locked Ti-sapphire laser, we collect simultaneous two-photon excited fluorescence (TPEF) and SHG images of retinal-stained kidney cells and cultured pyramidal neurons. Patch clamp experiments on neurons stained with retinal show an increase of 25\%in SHG intensity per 100-mV depolarization. Our data are the first demonstration of optical measurements of membrane potential of mammalian neurons with SHG. SHRIMP could have wide applicability in neuroscience and, by modifying rhodopsin, could in principle be subject for developing genetically engineered voltage sensors.}, Author = {Nemet, Boaz A. and Nikolenko, Volodymyr and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1083-3668}, Journal = {J Biomed Opt}, Keywords = {Staining and Labeling;Microscopy, Confocal;Retinaldehyde;Rats, Sprague-Dawley;Patch-Clamp Techniques;21 Neurophysiology;24 Pubmed search results 2008;Rats;21 Calcium imaging;evaluation studies;Animals, Newborn;Kidney;Animals;Image Enhancement;Cells, Cultured;Neurons;Membrane Potentials}, Nlm_Id = {9605853}, Number = {5}, Organization = {Columbia University, Department of Biological Sciences, 1212 Amsterdam Avenue, New York, New York 10027, USA. bn2010\@columbia.edu}, Pages = {873-81}, Pubmed = {15447008}, Title = {Second harmonic imaging of membrane potential of neurons with retinal}, Uuid = {C0511D49-AF75-404C-B8F5-649AD68CD2E4}, Volume = {9}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1117/1.1783353}} @article{Ness:2001, Abstract = {Hypoxia-ischemia (HI) is a leading cause of white matter damage, a major contributor to cerebral palsy in premature infants. Preferential white matter damage is believed to result from vulnerability of the immature oligodendrocyte (the pro-OL) to factors elevated during ischemic damage, such as oxygen free radicals and glutamate. In order to determine whether pro-OLs undergo apoptotic death after HI, we analyzed periventricular white matter OLs in P7 rats 4, 12 and 24 h after HI to analyze the time course and mode of cell death. DNA fragmentation was seen at 12 and 24 h of recovery after HI, representing a 17-fold increase over control. In addition, caspase-3 activation was found in NG2+ pro-OLs at 12 h. Electron-microscopic analysis of cell death in the white matter revealed a transition from early necrotic deaths to hybrid cell deaths to classical apoptosis between 4 and 24 h of recovery from HI. The delayed time course of apoptosis in pro-OLs supports the feasibility of interventions to improve clinical outcomes for newborns surviving birth asphyxia. 21481705 0378-5866 Journal Article}, Author = {Ness, J. K. and Romanko, M. J. and Rothstein, R. P. and Wood, T. L. and Levison, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Dev Neurosci}, Keywords = {Pregnancy;Caspases/metabolism;Neurotoxins;Hypoxia-Ischemia, Brain/*pathology;Rats;Female;Animal;Rats, Wistar;G abstr;11 Glia;Oligodendroglia/enzymology/*pathology/ultrastructure;Cerebral Ventricles/pathology;Stem Cells/enzymology/*pathology/ultrastructure;*Apoptosis;Support, Non-U.S. Gov't;Cerebral Palsy/pathology;Support, U.S. Gov't, P.H.S.;Microscopy, Electron}, Number = {3}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University, College of Medicine, Hershey, Pa 17033, USA.}, Pages = {203-8}, Pubmed = {11598321}, Title = {Perinatal hypoxia-ischemia induces apoptotic and excitotoxic death of periventricular white matter oligodendrocyte progenitors}, Uuid = {4988609D-536E-4216-8AE7-12E4DDA8A8F3}, Volume = {23}, Year = {2001}, url = {papers/Ness_DevNeurosci2001.pdf}} @article{Nestor:2007, Abstract = {Ephrin (Eph) signaling via Eph receptors affects neuronal structure and function. We report here that exogenous ephrinAs (EphAs) induce outgrowth of filopodial processes from astrocytes within minutes in rat hippocampal slice cultures. Identical effects were induced by release of endogenous ephrinAs by cleavage of their glycosylphosphatidylinositol anchor. Reverse transcription-PCR and immunocytochemistry revealed the expression of multiple EphA receptors (EphARs) in astrocytes. Exogenous and endogenous ephrins did not induce process outgrowth from astrocytes transfected with a kinase-dead EphAR construct, indicating that the critical EphARs were located on glia. Concomitant with these morphological changes, ephrinA reduced the frequency of (S)-3,5-dihydroxyphenylglycine-evoked NMDA receptor-mediated inward currents in CA1 pyramidal cells, elicited by release of glutamate from glial cells. The sensitivity of CA1 cell synaptic or extrasynaptic NMDA receptors was unaffected by ephrinA, indicating that this effect was mediated by inhibition of glutamate release from glial cells. Finally, ephrinA application decreased the frequency and increased the duration of spontaneous oscillations of the intracellular [Ca2+] in astrocytes. We conclude that ephrinA-EphA signaling is a pluripotent regulator of neuron-astrocyte interactions mediating rapid structural and functional plasticity.}, Author = {Nestor, Michael W. and Mok, Lee-Peng P. and Tulapurkar, Mohan E. and Thompson, Scott M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;Animals;Astrocytes;Cells, Cultured;Humans;Rats;Neuronal Plasticity;comparative study;Receptors, Eph Family;Cell Communication;Mice, Transgenic;Mice, Inbred C57BL;10 circuit formation;Animals, Newborn;Neuroglia;Neurons;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8102140}, Number = {47}, Organization = {Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. mnest001\@umaryland.edu}, Pages = {12817-28}, Pii = {27/47/12817}, Pubmed = {18032653}, Title = {Plasticity of neuron-glial interactions mediated by astrocytic EphARs}, Uuid = {4770548F-8165-46D5-94AC-4AF0205BC3D1}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2442-07.2007}} @article{Neuhaus:1994, Abstract = {Microglia develop in cultures initiated from disaggregated neopallial cells of newborn C3H/HeJ mice when the cultures are subjected to nutritional deprivation for 10 or more days (Hao et al: Int J Dev Neurosci 9:1-14, 1991). In the present experiments, the cultures were pulsed with BrdU for 3 hours at different times during incubation and then the cells were immunoreacted with antibodies against BrdU, GFAP, and CR3 receptor. The dividing cells (BrdU+) were found to be either GFAP+ or GFAP-, but not Mac-1+/BrdU+. Infection of proliferating cells after 2 or more days of incubation with replication-deficient retroviral vector containing E. coli lacZ reporter gene resulted in many labeled astroglia cell clones but no labeled microglia. However, when cells were infected right after disaggregation of neopallium, labeled Mac-1+ microglia were found. When Mac-1+ cells in a suspension of disaggregated neopallial cells were killed using complement mediated lysis before setting up the cultures, Mac-1+ microglia developed, in spite of the treatment. We conclude that in cultures initiated from mouse neopallium there are MAC-1-/GFAP- microglia progenitor cells which do not divide in nutritionally deprived cultures but can transform into Mac-1+ microglia under the influence of astroglia-derived trophic factors. Microglia, which become Mac-1+ (i.e., express CR3 receptor), proliferate extensively in the presence of CSF-1 (which is produced by astroglia).}, Author = {Neuhaus, J. and Fedoroff, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Mice;Clone Cells;Globus Pallidus;Research Support, Non-U.S. Gov't;Glial Fibrillary Acidic Protein;Astrocytes;Retroviridae;Cell Division;Stem Cells;11 Glia;Microglia;Culture Media;Mice, Inbred C3H;Bromodeoxyuridine;24 Pubmed search results 2008;Animals;Escherichia coli}, Medline = {94350462}, Month = {5}, Nlm_Id = {8806785}, Number = {1}, Organization = {Department of Anatomy, University of Saskatchewan, Saskatoon, Canada.}, Pages = {11-7}, Pubmed = {8070891}, Title = {Development of microglia in mouse neopallial cell cultures}, Uuid = {9CB07530-796B-4B0A-A4F7-C7852F5D8ACD}, Volume = {11}, Year = {1994}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.440110104}} @article{Neuhuber:2004, Abstract = {Bone marrow stromal cells (MSC), which represent a population of multipotential mesenchymal stem cells, have been reported to undergo rapid and robust transformation into neuron-like phenotypes in vitro following treatment with chemical induction medium including dimethyl sulfoxide (DMSO; Woodbury et al. [2002] J. Neurosci. Res. 96:908). In this study, we confirmed the ability of cultured rat MSC to undergo in vitro osteogenesis, chondrogenesis, and adipogenesis, demonstrating differentiation of these cells to three mesenchymal cell fates. We then evaluated the potential for in vitro neuronal differentiation of these MSC, finding that changes in morphology upon addition of the chemical induction medium were caused by rapid disruption of the actin cytoskeleton. Retraction of the cytoplasm left behind long processes, which, although strikingly resembling neurites, showed essentially no motility and no further elaboration during time-lapse studies. Similar neurite-like processes were induced by treating MSC with DMSO only or with actin filament-depolymerizing agents. Although process formation was accompanied by rapid expression of some neuronal and glial markers, the absence of other essential neuronal proteins pointed toward aberrantly induced gene expression rather than toward a sequence of gene expression as is required for neurogenesis. Moreover, rat dermal fibroblasts responded to neuronal induction by forming similar processes and expressing similar markers. These studies do not rule out the possibility that MSC can differentiate into neurons; however, we do want to caution that in vitro differentiation protocols may have unexpected, misleading effects. A dissection of molecular signaling and commitment events may be necessary to verify the ability of MSC transdifferentiation to neuronal lineages.}, Author = {Neuhuber, Birgit and Gallo, Gianluca and Howard, Linda and Kostura, Lisa and Mackay, Alastair and Fischer, Itzhak}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Biological Markers;Cell Differentiation;Embryonic Induction;Animals;Cells, Cultured;Gene Expression Regulation, Developmental;Rats;Phenotype;Fibroblasts;Osteogenesis;Chondrogenesis;Neurites;08 Aberrant cell cycle;Microfilaments;Research Support, U.S. Gov't, P.H.S.;Bone Marrow Cells;Cell Lineage;Neurons;Actins;Adipocytes;Culture Media;Stromal Cells;Nerve Tissue Proteins;Growth Substances}, Month = {7}, Nlm_Id = {7600111}, Number = {2}, Organization = {Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.}, Pages = {192-204}, Pubmed = {15211586}, Title = {Reevaluation of in vitro differentiation protocols for bone marrow stromal cells: disruption of actin cytoskeleton induces rapid morphological changes and mimics neuronal phenotype}, Uuid = {4A92069A-85B0-4580-9B9F-7A7E2C3F64FD}, Volume = {77}, Year = {2004}, url = {papers/Neuhuber_JNeurosciRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20147}} @article{Neumann:2006, Abstract = {Many neurological insults are accompanied by a marked acute inflammatory reaction, involving the activation of microglia. Using a model of exogenous application of fluorescence-labeled BV2 microglia in pathophysiologically relevant concentrations onto organotypic hippocampal slice cultures, we investigated the specific effects of microglia on neuronal damage after ischemic injury. Neuronal cell death after oxygen-glucose deprivation (OGD) was determined by propidium iodide incorporation and Nissl staining. Migration and interaction with neurons were analyzed by time resolved 3-D two-photon microscopy. We show that microglia protect against OGD-induced neuronal damage and engage in close physical cell-cell contact with neurons in the damaged brain area. Neuroprotection and migration of microglia were not seen with integrin regulator CD11a-deficient microglia or HL-60 granulocytes. The induction of migration and neuron-microglia interaction deep inside the slice was markedly increased under OGD conditions. Lipopolysaccharide-prestimulated microglia failed to provide neuroprotection after OGD. Pharmacological interference with microglia function resulted in a reduced neuroprotection. Microglia proved to be neuroprotective even when applied up to 4 h after OGD, thus defining a "protective time window." In acute injury such as trauma or stroke, appropriately activated microglia may primarily have a neuroprotective role. Anti-inflammatory treatment within the protective time window of microglia would therefore be counterintuitive.}, Author = {Neumann, and Gunzer, and Gutzeit, and Ullrich, and Reymann, and Dinkel,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {11 Glia}, Month = {2}, Nlm_Id = {8804484}, Pii = {05-4882fje}, Pubmed = {16473887}, Title = {Microglia provide neuroprotection after ischemia}, Uuid = {624E6294-B752-4B99-A930-7F6968E54294}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.05-4882fje}} @article{Neumann:2006a, Abstract = {Metachromatic leukodystrophy (MLD) is a lysosomal storage disease caused by deficiency of the enzyme arylsulfatase A (ARSA). MLD is characterized by progressive demyelination and neurological deficits. Treatment of MLD is still a challenge due to the fact that the blood-brain barrier is a major obstacle for most therapeutic substances. In this issue of the JCI, Biffi et al. report that genetically modified hematopoietic precursor cells transduced to overexpress ARSA and transplanted into mice with a targeted disruption of the murine Arsa gene (Arsa(-/-) mice) migrated into the CNS and cross-corrected brain ARSA deficiency (see the related article beginning on page 3070). Microglia served as a cellular vehicle to effectively deliver the enzyme to other brain cells while hepatocytes overexpressing ARSA increased plasma ARSA levels but failed to deliver ARSA into the CNS.}, Author = {Neumann, Harald}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0021-9738}, Journal = {J Clin Invest}, Keywords = {Cell Differentiation;research support, non-u.s. gov't;Central Nervous System;Blood-Brain Barrier;Hematopoietic Stem Cells;11 Glia;Microglia;comment;Gene Therapy;Animals;Leukodystrophy, Metachromatic;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {7802877}, Number = {11}, Organization = {Neural Regeneration Unit, Institute of Reconstructive Neurobiology, University of Bonn, and LIFE & BRAIN Center and Hertie Foundation, Bonn, Germany. hneuman1\@uni-bonn.de}, Pages = {2857-60}, Pubmed = {17080190}, Title = {Microglia: a cellular vehicle for CNS gene therapy}, Uuid = {6C3D6D31-1EB2-4000-893E-6883E0479859}, Volume = {116}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1172/JCI30230}} @article{Neumann:2002, Abstract = {In response to injury and inflammation of the CNS, brain cells including microglia and astrocytes secrete tumor necrosis factor-alpha (TNF). This pro-inflammatory cytokine has been implicated in both neuronal cell death and survival. We now provide evidence that TNF affects the formation of neurites. Neurons cultured on astrocytic glial cells exhibited reduced outgrowth and branching of neurites after addition of recombinant TNF or prestimulation of glial cells to secrete TNF. This effect was absent in neurons of TNF receptor-deficient mice cultured on prestimulated glia of wild-type mice and was reverted by blocking TNF with soluble TNF receptor IgG fusion protein. TNF activated in neurons the small GTPase RhoA. By inactivating Rho with C3 transferase, the inhibitory effect of TNF on neurite outgrowth and branching was abolished. These results suggest that glia-derived TNF, as part of an injury or inflammatory process, can inhibit neurite elongation and branching during development and regeneration.}, Author = {Neumann, Harald and Schweigreiter, Rudiger and Yamashita, Toshihide and Rosenkranz, Katja and Wekerle, Hartmut and Barde, Yves-Alain A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Survival;Research Support, Non-U.S. Gov't;Animals;Cells, Cultured;Coculture Techniques;Tumor Necrosis Factor-alpha;Beta;Interferon Type II;Antigens, CD;Cell Count;Neurites;Hippocampus;Mice, Inbred C57BL;11 Glia;Receptors, Tumor Necrosis Factor;Reverse Transcriptase Polymerase Chain Reaction;rhoA GTP-Binding Protein;Receptors, Tumor Necrosis Factor, Type II;Mice, Knockout;Neuroglia;Interleukin-1;Neurons;Botulinum Toxins;Mice;ADP Ribose Transferases;Receptors, Tumor Necrosis Factor, Type I}, Medline = {21683824}, Month = {2}, Nlm_Id = {8102140}, Number = {3}, Organization = {Departments of Neuroimmunology and Neurobiochemistry, Max-Planck Institute of Neurobiology, 82152 Martinsried, Germany.}, Pages = {854-62}, Pii = {22/3/854}, Pubmed = {11826115}, Title = {Tumor necrosis factor inhibits neurite outgrowth and branching of hippocampal neurons by a rho-dependent mechanism}, Uuid = {A699FC32-F904-4A3E-AF33-E2C61752CECD}, Volume = {22}, Year = {2002}} @article{Neumann:2008, Abstract = {Microglial cells maintain the immunological integrity of the healthy brain and can exert protection from traumatic injury. During ischemic tissue damage such as stroke, peripheral immune cells acutely infiltrate the brain and may exacerbate neurodegeneration. Whether and how microglia can protect from this insult is unknown. Polymorphonuclear neutrophils (PMNs) are a prominent immunologic infiltrate of ischemic lesions in vivo. Here, we show in organotypic brain slices that externally applied invading PMNs massively enhance ischemic neurotoxicity. This, however, is counteracted by additional application of microglia. Time-lapse imaging shows that microglia exert protection by rapid engulfment of apoptotic, but, strikingly, also viable, motile PMNs in cell culture and within brain slices. PMN engulfment is mediated by integrin- and lectin-based recognition. Interference with this process using RGDS peptides and N-acetyl-glucosamine blocks engulfment of PMNs and completely abrogates the neuroprotective function of microglia. Thus, engulfment of invading PMNs by microglia may represent an entirely new mechanism of CNS immune privilege.}, Author = {Neumann, Jens and Sauerzweig, Steven and R{\"o}nicke, Raik and Gunzer, Frank and Dinkel, Klaus and Ullrich, Oliver and Gunzer, Matthias and Reymann, Klaus G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Neurons;Phagocytosis;24 Pubmed search results 2008;research support, non-u.s. gov't;Central Nervous System;Rats;Rats, Wistar;Microglia;comparative study;Neutrophils;Animals;Cell Movement;Cells, Cultured;Immunity, Cellular;Mice}, Month = {6}, Nlm_Id = {8102140}, Number = {23}, Organization = {Leibniz Institute for Neurobiology, Project Group Neuropharmacology, Otto von Guericke University Magdeburg, 39118 Magdeburg, Germany. jens.neumann\@sciencetoday.de}, Pages = {5965-75}, Pii = {28/23/5965}, Pubmed = {18524901}, Title = {Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege}, Uuid = {9C7C341F-3891-479C-94D2-D8C691A75BFB}, Volume = {28}, Year = {2008}, url = {papers/Neumann_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0060-08.2008}} @article{Neves:2008, Abstract = {The role of cell size and shape in controlling local intracellular signaling reactions, and how this spatial information originates and is propagated, is not well understood. We have used partial differential equations to model the flow of spatial information from the beta-adrenergic receptor to MAPK1,2 through the cAMP/PKA/B-Raf/MAPK1,2 network in neurons using real geometries. The numerical simulations indicated that cell shape controls the dynamics of local biochemical activity of signal-modulated negative regulators, such as phosphodiesterases and protein phosphatases within regulatory loops to determine the size of microdomains of activated signaling components. The model prediction that negative regulators control the flow of spatial information to downstream components was verified experimentally in rat hippocampal slices. These results suggest a mechanism by which cellular geometry, the presence of regulatory loops with negative regulators, and key reaction rates all together control spatial information transfer and microdomain characteristics within cells.}, Author = {Neves, Susana R. and Tsokas, Panayiotis and Sarkar, Anamika and Grace, Elizabeth A. and Rangamani, Padmini and Taubenfeld, Stephen M. and Alberini, Cristina M. and Schaff, James C. and Blitzer, Robert D. and Moraru, Ion I. and Iyengar, Ravi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {Models, Biological;Cyclic AMP;Fetus;Hippocampus;Rats;Metabolic Networks and Pathways;Feedback, Biochemical;Aplysia;research support, n.i.h., extramural;Cell Shape;MAP Kinase Signaling System;Animals;Isoproterenol;Receptors, Adrenergic, beta-2;Neurons;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0413066}, Number = {4}, Organization = {Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1215, New York, NY 10029, USA.}, Pages = {666-80}, Pii = {S0092-8674(08)00517-5}, Pubmed = {18485874}, Title = {Cell shape and negative links in regulatory motifs together control spatial information flow in signaling networks}, Uuid = {7AAAD56D-CD98-4D9F-A4CD-F07D5AE104AD}, Volume = {133}, Year = {2008}, url = {papers/Neves_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.04.025}} @article{Ng:2001, Abstract = {PURPOSE: To explore the effects of light exposure and deprivation on the distribution and function of microglia in the subretinal space of mice. METHODS: Using a monoclonal antibody, 5D4, that identifies resting, ramified microglia, the distribution and density of microglia in the retina, and the subretinal space were determined by confocal microscopy and by immunohistochemistry of cryopreserved sections of eyes of albino and pigmented mice exposed to diverse levels of light, ranging from complete darkness to intense brightness. Axotomized retinal ganglion cells were retrograde labeled by fluorescent tracer to determine whether the marker colocalizes to 5D4+ cells. Electron microscopy was used to evaluate microglia for evidence of phagocytosis. RESULTS: 5D4+ microglia in pigmented eyes were limited to the inner retinal layers, but in albino eyes 5D4+ cells were found in the outer retinal layers and subretinal space as well. The subretinal space of eyes of albino mice raised from birth in complete darkness contained few 5D4+ cells, but exposure to light caused the rapid accumulation of 5D4+ cells at this site. 5D4+ cell density in the subretinal space correlated directly with intensity of ambient light. Retrograde labeling of axotomized ganglion cells resulted in 5D4+ cells in the subretinal space that contained the retrograde label. Subretinal microglia contained phagocytized rod outer segment discs. On intense light exposure, 5D4+ cells adopted an active morphology, but failed to express class II major histocompatibility complex (MHC) molecules. CONCLUSIONS: Light exposure induced retinal microglia migration into the subretinal space in albino mice. Subretinal microglia appeared to augment through phagocytosis the capacity of pigment epithelium to take up the photoreceptor debris of light toxicity. The unexpected presence of these cells in the subretinal space raises questions concerning their potential contribution to immune privilege in this space and to the fate of retinal transplants.}, Author = {Ng, T. F. and Streilein, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0146-0404}, Journal = {Invest Ophthalmol Vis Sci}, Keywords = {Retina;Phagocytosis;Animals;Microglia;Cell Count;Cell Movement;Reference Values;Not relevant;11 Glia;Eye Color;Support, Non-U.S. Gov't;Mice, Inbred Strains;Antibodies, Monoclonal;Light;Albinism;Support, U.S. Gov't, P.H.S.;Mice;Dose-Response Relationship, Radiation}, Medline = {21583626}, Month = {12}, Nlm_Id = {7703701}, Number = {13}, Organization = {Department of Ophthalmology, Schepens Eye Research Institute, 20 Staniford Street, Boston, MS 02114, USA.}, Pages = {3301-10}, Pubmed = {11726637}, Title = {Light-induced migration of retinal microglia into the subretinal space}, Uuid = {E32E389B-D247-4842-B2D2-4D0DC7FDF83E}, Volume = {42}, Year = {2001}} @article{Ng:2005, Abstract = {Neurogenesis persists in the olfactory bulb (OB) of the adult mammalian brain. New interneurons are continually added to the OB from the subventricular zone (SVZ) via the rostral migratory stream (RMS). Here we show that secreted prokineticin 2 (PK2) functions as a chemoattractant for SVZ-derived neuronal progenitors. Within the OB, PK2 may also act as a detachment signal for chain-migrating progenitors arriving from the RMS. PK2 deficiency in mice leads to a marked reduction in OB size, loss of normal OB architecture, and the accumulation of neuronal progenitors in the RMS. These findings define an essential role for G protein-coupled PK2 signaling in postnatal and adult OB neurogenesis.}, Author = {Ng, Kwan L. and Li, Jia-Da D. and Cheng, Michelle Y. and Leslie, Frances M. and Lee, Alex G. and Zhou, Qun-Yong Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Signal Transduction;Animals;Dopamine;Coculture Techniques;Rats;Chemotaxis;Apoptosis;Brain;Cell Count;Rats, Sprague-Dawley;Receptors, G-Protein-Coupled;Mice, Inbred C57BL;Gastrointestinal Hormones;Cell Proliferation;Neuropeptides;Olfactory Bulb;Cerebral Ventricles;Cell Adhesion;Cell Line;Neurons;Mice;Interneurons;24 Pubmed search results 2008;Chemotactic Factors;Stem Cells;Gene Expression}, Month = {6}, Nlm_Id = {0404511}, Number = {5730}, Organization = {Department of Pharmacology, University of California-Irvine (UCI), Irvine, CA 92697, USA.}, Pages = {1923-7}, Pii = {308/5730/1923}, Pubmed = {15976302}, Title = {Dependence of olfactory bulb neurogenesis on prokineticin 2 signaling}, Uuid = {E3D2E2D6-3C03-44E0-8527-F4624628DFED}, Volume = {308}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1112103}} @article{Nguyen:2002, Abstract = {A large body of evidence shows that molecular cues promote specific synapse formation by guiding axons and by mediating their association with targets, but much less is known about the contribution of physical cues (such as mechanical constraints) to these processes. Here we used the peripheral motor system to investigate the latter issue. In living mice, we viewed individual motor axons bearing a fluorescent reporter, and mapped the cohort of muscle fibers that they innervated both before and after nerve damage. When gross trauma was minimized (by a nerve-crushing rather than nerve-cutting procedure), regenerating axons retraced their former pathways, bifurcated at original branch points, and formed neuromuscular junctions on the same fibers that they originally innervated. Axonal growth through tubes of non-neural cells seemed to account for this specificity, and specificity degraded when the tubes were cut. These results suggest that nonspecific guidance cues can be sufficient to generate specific synaptic circuitry.}, Author = {Nguyen, Quyen T. and Sanes, Joshua R. and Lichtman, Jeff W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Animals;Basement Membrane;Bacterial Proteins;Efferent Pathways;Recovery of Function;Neuronal Plasticity;research support, u.s. gov't, p.h.s. ;Cell Communication;Mice, Transgenic;Green Fluorescent Proteins;Nerve Growth Factors;Nerve Regeneration;research support, non-u.s. gov't ;Receptors, Cholinergic;Neuromuscular Junction;21 Neurophysiology;Muscle, Skeletal;Motor Neurons;Mice;Nerve Crush;24 Pubmed search results 2008;Luminescent Proteins;Growth Cones;Ranvier's Nodes;Peripheral Nerves}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, MO 63110, USA.}, Pages = {861-7}, Pii = {nn905}, Pubmed = {12172551}, Title = {Pre-existing pathways promote precise projection patterns}, Uuid = {9C93837D-4A90-4713-A22A-2465C243EB17}, Volume = {5}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn905}} @article{Nguyen-Ba-Charvet:2004, Abstract = {The subventricular zone (SVZ) contains undifferentiated cells, which proliferate and generate olfactory bulb (OB) interneurons. Throughout life, these cells leave the SVZ and migrate along the rostral migratory stream (RMS) to the OB where they differentiate. In vitro, the septum and the choroid plexus (CP) secrete repulsive factors that could orient the migration of OB precursors. Slit1 and Slit2, two known chemorepellents for developing axons, can mimic this effect. We show here that the Slit receptors Robo2 and Robo3/Rig-1 are expressed in the SVZ and the RMS and that Slit1 and Slit2 are still present in the adult septum. Using Slit1/2-deficient mice, we found that Slit1 and Slit2 are responsible for both the septum and the CP repulsive activity in vitro. In adult mice lacking Slit1, small chains of SVZ-derived cells migrate caudally into the corpus callosum, supporting a role for Slits in orienting the migration of SVZ cells. Surprisingly, in adult mice, Slit1 was also expressed by type A and type C cells in the SVZ and RMS, suggesting that Slit1 could act cell autonomously. This hypothesis was tested using cultures of SVZ explants or isolated neurospheres from Slit1-/- or Slit1+/- mice. In both types of cultures, the migration of SVZ cells was altered in the absence of Slit1. This suggests that the regulation of the migration of OB precursors by Slit proteins is complex and not limited to repulsion. 1529-2401 Journal Article}, Author = {Nguyen-Ba-Charvet, K. T. and Picard-Riera, N. and Tessier-Lavigne, M. and Baron-Van Evercooren, A. and Sotelo, C. and Chedotal, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {J Neurosci}, Keywords = {B pdf;02 Adult neurogenesis migration}, Number = {6}, Organization = {Institut National de la Sante et de la Recherche Medicale U106, Batiment de Pediatrie, Hopital de la Salpetriere, 75013 Paris, France.}, Pages = {1497-506}, Title = {Multiple roles for slits in the control of cell migration in the rostral migratory stream}, Uuid = {09FE2BF0-E474-4AE0-9A05-BF4AF1F5AA94}, Volume = {24}, Year = {2004}, url = {papers/Nguyen-Ba-Charvet_JNeurosci2004.pdf}} @article{Nicholas:2002, Abstract = {Biodegradable microspheres made with poly-[D,L-lactide-co-glycolide] represent an evolving technology for drug delivery into the central nervous system. Even though these microspheres have been shown to be engulfed by astrocytes in vitro, the purpose of the present study was to track the fate of biodegradable microspheres in vivo. This was accomplished using microspheres containing the fluorescent dye coumarin-6 followed 1 day, 1 week and 1 month after intracerebral injections of this material were made into the rat brain. Using dual color immunohistochemistry and antisera against glial fibrillary acidic protein for astrocytes versus phosphotyrosine for microglia, results demonstrate that phagocytosis of small coumarin-containing microspheres <7.5 microm in diameter was primarily by microglia in vivo during the first week post-injection. In contrast, only a small minority of these microspheres appeared to be engulfed by astrocytes.}, Author = {Nicholas, Anthony P. and McInnis, Carey and Gupta, Kiran B. and Snow, William W. and Love, Darryl F. and Mason, David W. and Ferrell, Teresa M. and Staas, Jay K. and Tice, Thomas R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Biocompatible Materials;Research Support, Non-U.S. Gov't;Rats, Sprague-Dawley;Lactic Acid;Polyglycolic Acid;Rats;Polymers;Astrocytes;11 Glia;Injections, Intraventricular;Microspheres;Animals;Brain;Male}, Medline = {21948072}, Month = {4}, Nlm_Id = {7600130}, Number = {2}, Organization = {Department of Neurology, University of Alabama at Birmingham and the Birmingham Veterans Administration Medical Center, 619 19th Street South, Birmingham, AL 35249-7340, USA. tony\@email.neuro.uab.edu}, Pages = {85-8}, Pii = {S0304394001025344}, Pubmed = {11950499}, Title = {The fate of biodegradable microspheres injected into rat brain}, Uuid = {E7C81010-1129-4B6A-9F18-FE00AA8DA8A7}, Volume = {323}, Year = {2002}} @article{Nicole:2001, Abstract = {The glial cell line-derived neurotrophic factor (GDNF) is first characterized for its trophic activity on dopaminergic neurons. Recent data suggested that GDNF could modulate the neuronal death induced by ischemia. The purpose of this study was to characterize the influence of GDNF on cultured cortical neurons subjected to two paradigms of injury (necrosis and apoptosis) that have been identified during cerebral ischemia and to determine the molecular mechanisms involved. First, we demonstrated that both neurons and astrocytes express the mRNA and the protein for GDNF and its receptor complex (GFRalpha-1 and c-Ret). Next, we showed that the application of recombinant human GDNF to cortical neurons and astrocytes induces the activation of the MAP kinase (MAPK) pathway, as visualized by an increase in the phosphorylated forms of extracellular signal-regulated kinases (ERKs). Thereafter, we demonstrated that GDNF fails to prevent apoptotic neuronal death but selectively attenuates slowly triggered NMDA-induced excitotoxic neuronal death via a direct effect on cortical neurons. To further characterize the neuroprotective mechanisms of GDNF against NMDA-mediated neuronal death, we showed that a pretreatment with GDNF reduces NMDA-induced calcium influx. This effect likely results from a reduction of NMDA receptor activity rather than an enhanced buffering or extrusion capacity for calcium. Finally, we also demonstrated that an ERKs activation pathway is necessary for GDNF-mediated reduction of the NMDA-induced calcium response. Together, these results describe a novel mechanism by which the activation of MAPK induced by GDNF modulates NMDA receptor activity, a mechanism that could be responsible for the neuroprotective effect of GDNF in acute brain injury.}, Author = {Nicole, O. and Ali, C. and Docagne, F. and Plawinski, L. and MacKenzie, E. T. and Vivien, D. and Buisson, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Brain Ischemia/metabolism;Calcium/*metabolism;Glycosylphosphatidylinositols/metabolism;Apoptosis/drug effects;Mitogen-Activated Protein Kinases/metabolism;Nerve Tissue Proteins/genetics/*metabolism/pharmacology;07 Excitotoxicity Apoptosis;Animal;N-Methylaspartate/antagonists &inhibitors/*metabolism/toxicity;Membrane Proteins/metabolism;MAP Kinase Signaling System/drug effects/*physiology;Receptor Protein-Tyrosine Kinases/genetics/metabolism;Neurons/cytology/drug effects/metabolism;Chelating Agents;Mice, Inbred Strains;Oxidation-Reduction/drug effects;Neuroprotective Agents/*metabolism/pharmacology;Proto-Oncogene Proteins/genetics/metabolism;Support, Non-U.S. Gov't;Phosphorylation/drug effects;Astrocytes/cytology/drug effects/metabolism;C;Cerebral Cortex/cytology/drug effects/metabolism;04 Adult neurogenesis factors;Mice;RNA, Messenger/metabolism;Necrosis}, Number = {9}, Organization = {Universite de Caen, Unite Mixte de Recherche, Centre National de la Recherche Scientifique 6551, 14074 Caen Cedex, France.}, Pages = {3024-33.}, Title = {Neuroprotection mediated by glial cell line-derived neurotrophic factor: involvement of a reduction of NMDA-induced calcium influx by the mitogen-activated protein kinase pathway}, Uuid = {1BCEA2D0-EE23-42A0-BE2D-67A2F1775D38}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11312287%20http://www.jneurosci.org/cgi/content/full/21/9/3024%20http://www.jneurosci.org/cgi/content/abstract/21/9/3024}} @article{Nicolini:2002, Abstract = {Transfer of therapeutic genes to human hematopoietic stem cells (HSCs) using complex vectors at clinically relevant efficiencies remains a major challenge. Recently we described a stable retroviral vector that sustains long-term expression of green fluorescent protein (GFP) and a human beta-globin gene in the erythroid progeny of transduced murine HSCs. We now report the efficient transduction of primitive human CD34(+) fetal liver or cord blood cells with this vector and expression of the beta-globin transgene in the erythroid progeny of these human cells for at least 2 months. After growth factor prestimulation and then a 2- to 3-day exposure to the virus, 35\%to 55\%GFP(+) progeny were seen in assays of transduced colony-forming cells, primitive erythroid precursors that generate large numbers of glycophorin A(+) cells in 3-week suspension cultures, and 6-week long-term culture-initiating cells. In immunodeficient mice injected with unselected infected cells, 5\%to 15\%of the human cells regenerated in the marrow (including the erythroid cells) were GFP(+) 3 and 6 weeks after transplantation. Importantly, the numbers of GFP(+) human lymphoid and either granulopoietic or erythroid cells in individual mice 6 weeks after transplantation were significantly correlated, indicative of the initial transduction of human multipotent cells with in vivo repopulating activity. Expression of the transduced beta-globin gene in human cells obtained directly from the mice or after their differentiation into erythroid cells in vitro was demonstrated by reverse transcriptase-polymerase chain reaction using specific primers. These experiments represent a significant step toward the realization of a gene therapy approach for human beta-globin gene disorders.}, Author = {Nicolini, Franck E. and Imren, Suzan and Oh, Il-Hoan H. and Humphries, R. Keith and Leboulch, Philippe and Fabry, Mary E. and Nagel, Ronald L. and Eaves, Connie J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Erythrocytes;Transgenes;Cell Differentiation;Animals;Globins;Cells, Cultured;Humans;Transfection;Liver;Retroviridae;Antigens, CD34;11 Glia;Reverse Transcriptase Polymerase Chain Reaction;Hematopoietic Stem Cell Transplantation;Green Fluorescent Proteins;Research Support, U.S. Gov't, P.H.S.;Genetic Vectors;Gene Therapy;Mice;Erythroid Progenitor Cells;Luminescent Proteins;Fetal Blood;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {22144000}, Month = {8}, Nlm_Id = {7603509}, Number = {4}, Organization = {Terry Fox Laboratory, British Columbia Cancer Agency and University of British Columbia, Vancouver, BC, Canada.}, Pages = {1257-64}, Pubmed = {12149206}, Title = {Expression of a human beta-globin transgene in erythroid cells derived from retrovirally transduced transplantable human fetal liver and cord blood cells}, Uuid = {539FF2CB-6977-403F-AD4A-54DC75F9E36C}, Volume = {100}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood-2002-02-0599}} @article{Nieoullon:2005, Abstract = {We previously showed that deletion of the cell surface molecule mCD24 resulted in an increased proliferation in adult subventricular zone (SVZ). Here, we report an increased PSA-NCAM+/TuJ1- population in the mCD24-/- in vivo SVZ as well as in vitro neurospheres. Isolated in vitro, these cells were able to generate neurospheres. Proliferation studies, using BrdU incorporation, showed an increased proliferation in P7 mCD24-/- SVZ and neurospheres. Using electron microscopy, the same cell types were identified in the in vivo SVZ as well as in vitro neurospheres from the WT and mCD24-/- mice. In mixed neurospheres, formed with WT and EGFP/KO cells (enhanced green fluorescent protein mCD24-/-), the WT environment was able to control the proliferation rate of the mCD24-/- cells, but was unable to regulate their differentiation. We concluded that mCD24 acts cell nonautonomously to regulate transit-amplifying cells proliferation and/or differentiation.}, Author = {Nieoullon, Vincent and Belvindrah, Richard and Rougon, Genevi\`{e}ve and Chazal, Genevi\`{e}ve}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {Cell Differentiation;Animals;Cells, Cultured;Tubulin;Antigens, CD;Mice, Inbred C57BL;Green Fluorescent Proteins;Cell Proliferation;Male;P-Selectin;Antigens, CD24;Animals, Newborn;Cell Lineage;Membrane Glycoproteins;Mice, Knockout;Neurons;Sialic Acids;Microscopy, Electron, Transmission;Mice;Neural Cell Adhesion Molecule L1;24 Pubmed search results 2008;Stem Cells;Lateral Ventricles;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {9100095}, Number = {3}, Organization = {Neurogen\`{e}se et Morphogen\`{e}se dans le D{\'e}veloppement et chez l'Adulte/Institut de Biologie du D{\'e}veloppement de Marseille, Centre National de la Recherche Scientifique, Marseilles, France.}, Pages = {462-74}, Pii = {S1044-7431(04)00248-9}, Pubmed = {15737737}, Title = {mCD24 regulates proliferation of neuronal committed precursors in the subventricular zone}, Uuid = {6828E463-2981-4F9F-A7EA-500D01A5F239}, Volume = {28}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2004.10.007}} @article{Niewmierzycka:2005, Abstract = {Integrin-linked kinase (Ilk) is a scaffold and kinase that links integrin receptors to the actin cytoskeleton and to signaling pathways involved in cell adhesion, migration, and extracellular matrix deposition. Targeted deletion of Ilk from embryonic mouse dorsal forebrain neuroepithelium results in severe cortical lamination defects resembling cobblestone (type II) lissencephaly. Defects in adult mutants include neuronal invasion of the marginal zone, downward displacement of marginal zone components, fusion of the cerebral hemispheres, and scalloping of the dentate gyrus. These lesions are associated with abundant astrogliosis and widespread fragmentation of the basal lamina at the cortical surface. During cortical development, neuronal ectopias are associated with severe disorganization of radial glial processes and displacement of Cajal-Retzius cells. Lesions are not seen when Ilk is specifically deleted from embryonic neurons. Interestingly, targeted Ilk deletion has no effect on proliferation or survival of cortical cells or on phosphorylation of two Ilk substrates, Pkb/Akt and Gsk-3beta, suggesting that Ilk does not regulate cortical lamination via these enzymes. Instead, Ilk acts in vivo as a major intracellular mediator of integrin-dependent basal lamina formation. This study demonstrates a critical role for Ilk in cortical lamination and suggests that Ilk-associated pathways are involved in the pathogenesis of cobblestone lissencephalies.}, Author = {Niewmierzycka, Agnieszka and Mills, Julia and St-Arnaud, Rene and Dedhar, Shoukat and Reichardt, Louis F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Month = {7}, Nlm_Id = {8102140}, Number = {30}, Organization = {Department of Pathology, University of California, San Francisco, California 94143, USA.}, Pages = {7022-31}, Pii = {25/30/7022}, Pubmed = {16049178}, Title = {Integrin-linked kinase deletion from mouse cortex results in cortical lamination defects resembling cobblestone lissencephaly}, Uuid = {AD8B1558-A3E5-11DA-AB00-000D9346EC2A}, Volume = {25}, Year = {2005}, url = {papers/Niewmierzycka_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1695-05.2005}} @article{Nikolenko:2007, Abstract = {We introduce an optical method to stimulate individual neurons in brain slices in any arbitrary spatiotemporal pattern, using two-photon uncaging of MNI-glutamate with beam multiplexing. This method has single-cell and three-dimensional precision. By sequentially stimulating up to a thousand potential presynaptic neurons, we generated detailed functional maps of inputs to a cell. We combined this approach with two-photon calcium imaging in an all-optical method to image and manipulate circuit activity.}, Author = {Nikolenko, Volodymyr and Poskanzer, Kira E. and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {Excitatory Postsynaptic Potentials;Electrophysiology;Calcium Signaling;Animals;Cytophotometry;Neocortex;Mice, Transgenic;Mice, Inbred C57BL;Tetrodotoxin;Indoles;research support, non-u.s. gov't;Glutamine;Acetates;Glutamates;Action Potentials;Nerve Net;Neurons;Microscopy, Fluorescence, Multiphoton;research support, n.i.h., extramural;Mice;Reproducibility of Results;24 Pubmed search results 2008;Brain Mapping}, Month = {11}, Nlm_Id = {101215604}, Number = {11}, Organization = {Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, Box 2435, New York, New York 10027, USA. vn59\@columbia.edu}, Pages = {943-50}, Pii = {nmeth1105}, Pubmed = {17965719}, Title = {Two-photon photostimulation and imaging of neural circuits}, Uuid = {AE8787E8-6D7F-4401-9B72-657D1F70DE6B}, Volume = {4}, Year = {2007}, url = {papers/Nikolenko_NatMethods2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth1105}} @article{Nilsen:2005, Abstract = {PURPOSE: To characterize in detail a model of focal neocortical epilepsy. METHODS: Chronic focal epilepsy was induced by injecting 25-50 ng of tetanus toxin or vehicle alone (controls) into the motor neocortex of rats. EEG activity was recorded from electrodes implanted at the injection site, along with facial muscle electromyographic (EMG) activity and behavioral monitoring intermittently for up to 5 months in some animals. Drug responsiveness was assessed by using the antiepileptic drugs (AEDs) diazepam (DZP) and phenytoin (PHT) delivered systemically, while 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), a competitive antagonist at AMPA receptors, was administered directly to the brain to investigate the potential benefits of focal drug delivery. RESULTS: Tetanus toxin induced mild behavioral seizures that persisted indefinitely in all animals. EEG spiking activity, occurring up to 80\%of the time, correlated with clinical seizures consisting of interrupted behavioral activity, rhythmic bilateral facial twitching, and periods of abrupt motor arrest. Seizures were refractory to systemic administration of DZP and PHT. However, focal delivery of NBQX to the seizure site reversibly reduced EEG and behavioral seizure activity without detectable side effects. CONCLUSIONS: This study provides a long-term detailed characterisation of the tetanus toxin model. Spontaneous, almost continuous, well-tolerated seizures occur and persist, resembling those seen in neocortical epilepsy, including cortical myoclonus and epilepsia partialis continua. The seizures appear to be similarly resistant to conventional AEDs. The consistency, frequency, and clinical similarity of the seizures to refractory epilepsy in humans make this an ideal model for investigation of both mechanisms of seizure activity and new therapeutic approaches.}, Author = {Nilsen, Karen E. and Walker, Matthew C. and Cock, Hannah R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Anticonvulsants;Diazepam;Motor Activity;Animals;Epilepsies, Partial;Rats;Brain;Exploratory Behavior;Neocortex;21 Epilepsy;Rats, Sprague-Dawley;Receptors, AMPA;Disease Models, Animal;Behavior, Animal;Male;Phenytoin;Quinoxalines;Electromyography;21 Neurophysiology;24 Pubmed search results 2008;Electroencephalography;Tetanus Toxin;Research Support, Non-U.S. Gov't}, Month = {2}, Nlm_Id = {2983306R}, Number = {2}, Organization = {Clinical Neurosciences (Epilepsy), Department of Cardiological Sciences, St. George's Hospital Medical School, London, England.}, Pages = {179-87}, Pii = {EPI26004}, Pubmed = {15679498}, Title = {Characterization of the tetanus toxin model of refractory focal neocortical epilepsy in the rat}, Uuid = {1F700F2C-3FD6-47FC-8790-25925257F9C6}, Volume = {46}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.0013-9580.2005.26004.x}} @article{Nimmerjahn:2004, Abstract = {Glial cells have been identified as key signaling components in the brain; however, methods to investigate their structure and function in vivo have been lacking. Here, we describe a new, highly selective approach for labeling astrocytes in intact rodent neocortex that allows in vivo imaging using two-photon microscopy. The red fluorescent dye sulforhodamine 101 (SR101) was specifically taken up by protoplasmic astrocytes after brief exposure to the brain surface. Specificity was confirmed by immunohistochemistry. In addition, SR101 labeled enhanced green fluorescent protein (EGFP)-expressing astrocytes but not microglial cells in transgenic mice. We used SR101 labeling to quantify morphological characteristics of astrocytes and to visualize their close association with the cortical microvasculature. Furthermore, by combining this method with calcium indicator loading of cell populations, we demonstrated distinct calcium dynamics in astroglial and neuronal networks. We expect SR101 staining to become a principal tool for investigating astroglia in vivo.}, Author = {Nimmerjahn, Axel and Kirchhoff, Frank and Kerr, Jason N. D. and Helmchen, Fritjof}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {Fluorescent Dyes;Rhodamines;Calcium Signaling;Astrocytes;Animals;Rats;Neocortex;Staining and Labeling;Mice, Inbred C57BL;Gap Junctions;Calcium;21 Calcium imaging;Rats, Wistar;Animals, Newborn;evaluation studies;21 Neurophysiology;Microscopy, Fluorescence, Multiphoton;Mice;24 Pubmed search results 2008;Biological Markers;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {101215604}, Number = {1}, Organization = {Abteilung Zellphysiologie, Max-Planck Institut f{\"u}r medizinische Forschung, Jahnstr. 29, 69120 Heidelberg, Germany.}, Pages = {31-7}, Pii = {nmeth706}, Pubmed = {15782150}, Title = {Sulforhodamine 101 as a specific marker of astroglia in the neocortex in vivo}, Uuid = {41F2A851-2E8F-41AF-A3D0-03C646D4D85C}, Volume = {1}, Year = {2004}, url = {papers/Nimmerjahn_NatMethods2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth706}} @article{Nimmerjahn:2005, Abstract = {Microglial cells represent the immune system of the brain and therefore are critically involved in various injuries and diseases. Little is known about their role in the healthy brain and their immediate reaction to brain damage. Using in vivo two-photon imaging in neocortex, we found that microglial cells are highly active in their presumed resting state, continually surveying their microenvironment with extremely motile processes and protrusions. Furthermore, blood brain barrier disruption provoked immediate and focal activation of microglia, switching their behavior from patrolling to shielding of the injured site. Microglia thus are busy and vigilant housekeepers in adult brain.}, Author = {Nimmerjahn, and Kirchhoff, and Helmchen,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Alpha;11 Glia}, Month = {5}, Nlm_Id = {0404511}, Number = {5726}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut f{\"u}r medizinische Forschung, Jahnstr. 29, 69120 Heidelberg, Germany.}, Pages = {1314-8}, Pii = {1110647}, Pubmed = {15831717}, Title = {Resting Microglial Cells Are Highly Dynamic Surveillants of Brain Parenchyma in Vivo}, Uuid = {CC67C274-9F64-11DA-8D49-000D9346EC2A}, Volume = {308}, Year = {2005}, url = {papers/Nimmerjahn_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1110647}} @article{Ninkovic:2007, Abstract = {Adult neurogenesis is restricted to two distinct areas of the mammalian brain: the olfactory bulb (OB) and the dentate gyrus (DG). Despite its spatial restriction, adult neurogenesis is of crucial importance for sensory processing and learning and memory. Although it has been shown that tens of thousands of new neurons arrive in the OB and DG every day with about half of them surviving after integration, the total contribution of adult neurogenesis to the pre-existing network remains mostly unknown. This is because of previous approaches labeling only a small proportion of adult-generated neurons. Here, we used genetic fate mapping to follow the majority of adult-generated neurons over long periods. Our data demonstrate two distinct modes of neuron addition to the pre-existing network. In the glomerular layer of the OB, there is a constant net addition of adult-generated neurons reaching a third of the total neuronal population within 9 months. In contrast, adult neurogenesis contributes to only a minor fraction of the entire neuronal network in the granular cell layer of the OB and the DG. Although the fraction of adult generated neurons can be further increased by an enriched environment, it still remains a minority of the neuronal network in the DG. Thus, neuron addition is distinct and tightly regulated in the neuronal networks that incorporate new neurons life long.}, Author = {Ninkovic, Jovica and Mori, Tetsuji and G{\"o}tz, Magdalena}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8102140}, Number = {40}, Organization = {Institute for Stem Cell Research, Gesellschaft f{\"u}r Strahlenforschung-National Research Institute for Environment and Health, 85764 Neuherberg/Munich, Germany.}, Pages = {10906-11}, Pii = {27/40/10906}, Pubmed = {17913924}, Title = {Distinct modes of neuron addition in adult mouse neurogenesis}, Uuid = {2090195B-EEBC-4C7D-BA9C-212F3FEE12AB}, Volume = {27}, Year = {2007}, url = {papers/Ninkovic_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2572-07.2007}} @article{Nir:2008, Abstract = {Animal studies have shown robust electrophysiological activity in the sensory cortex in the absence of stimuli or tasks. Similarly, recent human functional magnetic resonance imaging (fMRI) revealed widespread, spontaneously emerging cortical fluctuations. However, it is unknown what neuronal dynamics underlie this spontaneous activity in the human brain. Here we studied this issue by combining bilateral single-unit, local field potentials (LFPs) and intracranial electrocorticography (ECoG) recordings in individuals undergoing clinical monitoring. We found slow (<0.1 Hz, following 1/f-like profiles) spontaneous fluctuations of neuronal activity with significant interhemispheric correlations. These fluctuations were evident mainly in neuronal firing rates and in gamma (40-100 Hz) LFP power modulations. Notably, the interhemispheric correlations were enhanced during rapid eye movement and stage 2 sleep. Multiple intracranial ECoG recordings revealed clear selectivity for functional networks in the spontaneous gamma LFP power modulations. Our results point to slow spontaneous modulations in firing rate and gamma LFP as the likely correlates of spontaneous fMRI fluctuations in the human sensory cortex.}, Author = {Nir, and Mukamel, and Dinstein, and Privman, and Harel, and Fisch, and Gelbard-Sagiv, and Kipervasser, and Andelman, and Neufeld, and Kramer, and Arieli, and Fried, and Malach,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1546-1726}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {9809671}, Organization = {Department of Neurobiology, Weizmann Institute of Science, 240 Herzl Street, Rehovot 76100, Israel.}, Pii = {nn.2177}, Pubmed = {18711392}, Title = {Interhemispheric correlations of slow spontaneous neuronal fluctuations revealed in human sensory cortex}, Uuid = {2606D7D4-ADD5-4847-8F03-0C8453D3A0A3}, Year = {2008}, url = {papers/Nir_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2177}} @article{Nirenberg:2007, Abstract = {Understanding how the brain performs computations requires understanding neuronal firing patterns at successive levels of processing-a daunting and seemingly intractable task. Two recent studies have made dramatic progress on this problem by showing how its dimensionality can be reduced. Using the retina as a model system, they demonstrated that multineuronal firing patterns can be predicted by pairwise interactions.}, Author = {Nirenberg, Sheila H. and Victor, Jonathan D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {20 Networks;21 Neurophysiology;21 Calcium imaging;research support, n.i.h., extramural;21 Cortical oscillations;24 Pubmed search results 2008;review}, Month = {8}, Nlm_Id = {9111376}, Number = {4}, Organization = {Department of Physiology and Biophysics, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. shn201\@med.cornell.edu}, Pages = {397-400}, Pii = {S0959-4388(07)00085-2}, Pubmed = {17709240}, Title = {Analyzing the activity of large populations of neurons: how tractable is the problem?}, Uuid = {03CFBCEE-5F63-465B-8D00-4B88A26500A5}, Volume = {17}, Year = {2007}, url = {papers/Nirenberg_CurrOpinNeurobiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2007.07.002}} @article{Nishiike:2000, Abstract = {The distribution of cortical efferent connections to the vestibular nuclei was quantitatively analyzed by means of retrograde axonal transport of horseradish peroxidase, wheat germ agglutinin-horseradish peroxidase, and Fast Blue in rats. The tracer substances were injected into the spinal vestibular nucleus (SpVe), the caudal part of the medial vestibular nucleus (MVe), and nucleus X of Brown Norwegian rats. Projections to the vestibular nuclei were revealed bilaterally, but predominantly contralaterally from five cortical areas: (1) the parietotemporal region (PT) which occupied the caudal two-thirds of the secondary somatosensory area and spread over the caudal part of the primary somatosensory area and the visceral cortex; (2) the anterior forelimb (AF) overlapping the anterior part of the forelimb area and the transitional zone; (3) the anterior hindlimb (AH) overlapping the anterior part of the hindlimb area and the transitional zone; (4) the lateral forelimb (LF) centered in the intercalated zone lateral to the forelimb area; and (5) the ventrotemporal region (VT) located at the ventral part of the temporal cortex. In addition to these cortical fields, the frontal cortex was found to project directly to the vestibular nuclei. These corticofugal projections were verified in experiments in which biocytin was injected into the rat PT. Anterogradely labelled fibers were traced predominantly contralaterally to the SpVe, caudal part of the MVe, and nucleus X. It is suggested that the rat corticofugal projections to the caudal vestibular nuclei modify vestibular reflexes to assist in coordinating eye, head and body movements during locomotion.}, Author = {Nishiike, S. and Guldin, W. O. and B{\"a}urle, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Humans;Rats;Neural Pathways;Comparative Study;Vestibular Nuclei;Female;Axons;Cell Count;Male;Cerebral Cortex;Neurons;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Horseradish Peroxidase;Infant, Newborn;24 Pubmed search results 2008;Brain Mapping}, Medline = {20219220}, Month = {5}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Physiology, Freie Universit{\"a}t Berlin, 14195 Berlin, Germany. nishiike\@ebt.med.osaka-u.ac,jp}, Pages = {363-72}, Pii = {10.1002/(SICI)1096-9861(20000508)420:3<363::AID-CNE7>3.0.CO;2-X}, Pubmed = {10754508}, Title = {Corticofugal connections between the cerebral cortex and the vestibular nuclei in the rat}, Uuid = {8EAEF57F-9D1C-40FB-849C-8DCB3A5B9679}, Volume = {420}, Year = {2000}} @article{Nishikura:2001, Abstract = {One of the many intriguing features of gene silencing by RNA interference is the apparent catalytic nature of the phenomenon. New biochemical and genetic evidence now shows that an RNA-directed RNA polymerase chain reaction, primed by siRNA, amplifies the interference caused by a small amount of "trigger"dsRNA. 0092-8674 Journal Article Review Review, Tutorial}, Author = {Nishikura, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Cell}, Keywords = {Drosophila melanogaster/embryology/genetics;Gene Targeting;Animals;Plant Proteins/physiology;RNA, Untranslated/genetics/*physiology;Polymerase Chain Reaction/methods;Endoribonucleases/physiology;RNA Replicase/*physiology;23 Technique;Models, Genetic;Insect Proteins/physiology;RNA, Small Interfering;RNA, Messenger/*antagonists &inhibitors/genetics/metabolism;RNA Processing, Post-Transcriptional;RNA, Double-Stranded/pharmacology/physiology;T abstr;Cell-Free System;Sequence Homology, Nucleic Acid;Gene Silencing/*physiology;Ribonuclease III}, Number = {4}, Organization = {The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA. kazuko\@wistar.upenn.edu}, Pages = {415-8}, Pubmed = {11719182}, Title = {A short primer on RNAi: RNA-directed RNA polymerase acts as a key catalyst}, Uuid = {E6DF3360-200D-42C2-822D-BAFF630C7C68}, Volume = {107}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11719182}} @article{Nishiyama:2002, Abstract = {Cells that express the NG2 proteoglycan (NG2+ cells) comprise a unique population of glial cells in the central nervous system. While there is no question that some NG2+ cells differentiate into oligodendrocytes during development, the persistence of numerous NG2+ cells in the mature CNS has raised questions about their identity, relation to other CNS cell types, and functions besides their progenitor role. NG2+ cells also express the alpha receptor for platelet-derived growth factor (PDGF alphaR), a receptor that mediates oligodendrocyte progenitor proliferation during development. Antigenically, NG2+ cells are distinct from fibrous and protoplasmic astrocytes, resting microglia, and mature oligodendrocytes. Therefore, we propose the term polydendrocytes to refer to all NG2-expressing glial cells in the CNS parenchyma. This distinguishes them from the classical glial cell types and identifies them as the fourth major glial population in the CNS. Recent observations suggest that polydendrocytes are complex cells that physically and functionally interact with other cell types in the CNS. Committed oligodendrocyte progenitor cells arise from restricted foci in the ventral ventricular zone in both spinal cord and brain. It remains to be clarified whether there are multiple sources of oligodendrocytes, and if so whether polydendrocytes (NG2+ cells) represent progenitor cells of all oligodendrocyte lineages. Proliferation of NG2+ cells during early development appears to be dependent on PDGF, but the regulatory mechanisms that govern NG2+ cell proliferation in the mature CNS remain unknown. Pulse-chase labeling with bromodeoxyuridine indicates that polydendrocytes that proliferate in the postnatal spinal cord differentiate into oligodendrocytes. Novel experimental approaches are being developed to further elucidate the functional properties and differentiation potential of polydendrocytes. 0300-4864 Journal Article}, Author = {Nishiyama, A. and Watanabe, M. and Yang, Z. and Bu, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Neurocytol}, Keywords = {11 Glia;G pdf}, Number = {6-7}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, 3107 Horsebarn Hill Road, Unit 4156, Storrs, CT 06269-4156, USA. akiko.nishiyama\@uconn.edu}, Pages = {437-55}, Pubmed = {14501215}, Title = {Identity, distribution, and development of polydendrocytes: NG2-expressing glial cells}, Uuid = {157B3793-5E2D-4E12-959A-07E8A17571B0}, Volume = {31}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14501215}} @article{Nishiyama:1999, Abstract = {We describe a major glial cell population in the central nervous system (CNS) that can be identified by the expression of 2 cell surface molecules, the NG2 proteoglycan and the alpha receptor for platelet-derived growth factor (PDGF alphaR). In vitro and in the developing brain in vivo, NG2 and PDGF alphaR are expressed on oligodendrocyte progenitor cells but are down-regulated as the progenitor cells differentiate into mature oligodendrocytes. In the mature CNS, numerous NG2+/PDGF alphaR+ cells with extensive arborization of their cell processes are found ubiquitously long after oligodendrocytes are generated. NG2+ cells in the mature CNS do not express antigens specific to mature oligodendrocytes, astrocytes, microglia, or neurons, suggesting that they are a novel population of glial cells. Recently NG2+ cells in the adult CNS have been shown to undergo proliferation and morphological changes in response to a variety of stimuli, such as demyelination and inflammation, suggesting that they are dynamic cells capable of responding to changes in the environment. Furthermore, high levels of NG2+ and PDGF alphaR are expressed on oligodendroglioma cells, raising the possibility that the NG2+/PDGF alphaR+ cells in the mature CNS contribute to glial neoplasm. 0022-3069 Journal Article Review Review, Tutorial}, Author = {Nishiyama, A. and Chang, A. and Trapp, B. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Proteoglycans/*analysis;Antigens/*analysis;Brain Diseases/pathology;Brain/*cytology/pathology;Neuroglia/*chemistry/*cytology;11 Glia;Mice, Jimpy;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't;Age Factors;Mice;G}, Number = {11}, Organization = {Department of Neurosciences, The Lerner Research Institute, Cleveland Clinic Foundation, Ohio, USA.}, Pages = {1113-24}, Pubmed = {10560654}, Title = {NG2+ glial cells: a novel glial cell population in the adult brain}, Uuid = {EE9FA190-1B87-4E50-B5CF-539E62A333C5}, Volume = {58}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10560654}} @article{Nitz:2008, Author = {Nitz, Douglas and Cowen, Stephen}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9809671}, Number = {2}, Organization = {The authors are at The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, California 92121, USA. nitz\@nsi.edu.}, Pages = {126-8}, Pii = {nn0208-126}, Pubmed = {18227794}, Title = {Crossing borders: sleep reactivation as a window on cell assembly formation}, Uuid = {C46DEEA6-751B-4D23-BB9D-00A0BB80AC28}, Volume = {11}, Year = {2008}, url = {papers/Nitz_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0208-126}} @article{Niwa:1983, Abstract = {Expression and DNA methylation of the Moloney murine leukemia virus (M-MuLV) genome were investigated in murine teratocarcinoma cells after virus infection. The newly acquired viral genome was devoid of methylation, yet its expression was repressed. The integrated viral genome in undifferentiated teratocarcinoma cells was methylated within 15 days after infection. Although 5-azacytidine decreased the level of DNA methylation, it did not activate M-MuLV in undifferentiated cells. Activation by 5-azacytidine occurred only in differentiated teratocarcinoma cells. Thus two independent mechanisms seem to regulate gene expression during the course of differentiation. The first mechanism operates in undifferentiated cells to block expression of M-MuLV and other exogeneously acquired viral genes, such as SV40 and polyoma virus, and does not depend on DNA methylation. The second mechanism relates only to differentiated cells and represses expression of genes in which DNA is methylated.}, Author = {Niwa, O. and Yokota, Y. and Ishida, H. and Sugahara, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Transcription, Genetic;Teratoma;Cell Differentiation;Animals;Gene Expression Regulation;Transfection;Cell Cycle;15 Retrovirus mechanism;Methylation;Azacitidine;Genes, Viral;Cell Line;Moloney murine leukemia virus;Recombination, Genetic;DNA, Viral;Mice;24 Pubmed search results 2008;Bromodeoxyuridine;Tretinoin;Research Support, Non-U.S. Gov't}, Medline = {83180409}, Month = {4}, Nlm_Id = {0413066}, Number = {4}, Pages = {1105-13}, Pii = {0092-8674(83)90294-5}, Pubmed = {6188535}, Title = {Independent mechanisms involved in suppression of the Moloney leukemia virus genome during differentiation of murine teratocarcinoma cells}, Uuid = {43FB7583-F3B3-4A0D-9E94-CF3B304B9937}, Volume = {32}, Year = {1983}} @article{Noble:2003, Abstract = {Studies on the development of cortical oligodendrocytes indicate that although general principles that apply to other parts of the CNS are applicable, there are important differences that appear to be critical to the analysis of this lineage in the cortex. Herein, we review previous studies demonstrating that oligodendrocyte-type-2 astrocyte progenitor cells (or oligodendrocyte precursor cells; aka O-2A/OPCs) of the developing postnatal cortex exhibit a striking cell-intrinsic bias towards undergoing prolonged self-renewal in the relative absence of oligodendrocyte generation [Power et al., Dev Biol 2002;245:362-375]. This phenotype is quite distinct from that observed in comparable cells isolated from the optic tract. This predilection for self-renewal is associated with a lessened response to inducers of oligodendrocyte generation and of possible mechanistic importance in regards to these other properties. We also review studies on stem/progenitor cells isolated from the embryonic cortex that are able to generate oligodendrocytes. As for the studies on O-2A/OPCs, important differences also distinguish these early cells from those studied in other CNS regions in their response to signaling molecules and expression of the Dlx family of transcriptional regulators [He et al., J Neurosci 2001;21:8854-8862; Yung et al., Proc Natl Acad Sci USA 2002;99:16273-16278]. We also present new data on clonal analysis of A2B5+ precursor cells isolated from the E13.5 cortex, demonstrating that this tissue appears to contain a cell similar in properties to the tripotential glial-restricted precursor cell that has been isolated from embryonic spinal cord [Rao et al., Proc Natl Acad Sci USA 1998;95:3996-4001]. Moreover, the A2B5+ precursor cells isolated from embryonic cortex are much more heterogeneous than is seen in the spinal cord at this age, even to the point of including an A2B5/PSA-NCAM double-positive cell that can generate neurons.}, Author = {Noble, M. and Arhin, A. and Gass, D. and Mayer-Pr{\"o}schel, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Cell Differentiation;Research Support, Non-U.S. Gov't;Comparative Study;Research Support, U.S. Gov't, P.H.S.;Stem Cells;11 Glia;Spinal Cord;Animals;Oligodendroglia;Cerebral Cortex;Cell Lineage;Humans}, Medline = {22845919}, Nlm_Id = {7809375}, Number = {2-4}, Organization = {Department of Biomedical Genetics, University of Rochester Medical Center, Rochester, NY 14642, USA. Mark\_Noble\@urmc.rochester.edu}, Pages = {217-33}, Pii = {DNE20030252_4217}, Pubmed = {12966219}, Title = {The cortical ancestry of oligodendrocytes: common principles and novel features}, Uuid = {250CAF47-382C-4D1B-A9FA-CAB0BE55C147}, Volume = {25}, Year = {2003}, url = {papers/Noble_DevNeurosci2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000072270}} @article{Noctor:2002, Abstract = {The embryonic ventricular zone (VZ) of the cerebral cortex contains migrating neurons, radial glial cells, and a large population of cycling progenitor cells that generate newborn neurons. The latter two cell classes have been assumed for some time to be distinct in both function and anatomy, but the cellular anatomy of the progenitor cell type has remained poorly defined. Several recent reports have raised doubts about the distinction between radial glial and precursor cells by demonstrating that radial glial cells are themselves neuronal progenitor cells (Malatesta et al., 2000; Hartfuss et al., 2001; Miyata et al., 2001; Noctor et al., 2001). This discovery raises the possibility that radial glia and the population of VZ progenitor cells may be one anatomical and functional cell class. Such a hypothesis predicts that throughout neurogenesis almost all mitotically active VZ cells and a substantial percentage of VZ cells overall are radial glia. We have therefore used various anatomical, immunohistochemical, and electrophysiological techniques to test these predictions. Our data demonstrate that the majority of VZ cells, and nearly all mitotically active VZ cells during neurogenesis, both have radial glial morphology and express radial glial markers. In addition, intracellular dye filling of electrophysiologically characterized progenitor cells in the VZ demonstrates that these cells have the morphology of radial glia. Because the vast majority cycling cells in the cortical VZ have characteristics of radial glia, the radial glial precursor cell may be responsible for both the production of newborn neurons and the guidance of daughter neurons to their destinations in the developing cortex. 21940963 1529-2401 Journal Article}, Author = {Noctor, S. C. and Flint, A. C. and Weissman, T. A. and Wong, W. S. and Clinton, B. K. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;F;Cerebral Ventricles/*cytology;Biolistics;In Vitro;Rats;Mitosis;Stem Cells/*cytology/metabolism;Patch-Clamp Techniques;Animal;Rats, Sprague-Dawley;Microspheres;Support, Non-U.S. Gov't;Retroviridae/genetics;Vimentin/biosynthesis;Cerebral Cortex/*cytology/*embryology;Support, U.S. Gov't, P.H.S.;Pyramidal Cells/cytology/metabolism;Cell Division;Immunohistochemistry;S Phase;Antigens, Differentiation/biosynthesis;Neuroglia/*cytology;Cell Differentiation/physiology;Luminescent Proteins/biosynthesis/genetics}, Number = {8}, Organization = {Department of Neurology, Columbia College of Physicians and Surgeons, New York, New York 10032, USA.}, Pages = {3161-73}, Pubmed = {11943818}, Title = {Dividing precursor cells of the embryonic cortical ventricular zone have morphological and molecular characteristics of radial glia}, Uuid = {AE860DC7-71C2-11DA-A383-000D9346EC2A}, Volume = {22}, Year = {2002}, url = {papers/Noctor_JNeurosci2002.pdf}} @article{Noctor:2004, Abstract = {Precise patterns of cell division and migration are crucial to transform the neuroepithelium of the embryonic forebrain into the adult cerebral cortex. Using time-lapse imaging of clonal cells in rat cortex over several generations, we show here that neurons are generated in two proliferative zones by distinct patterns of division. Neurons arise directly from radial glial cells in the ventricular zone (VZ) and indirectly from intermediate progenitor cells in the subventricular zone (SVZ). Furthermore, newborn neurons do not migrate directly to the cortex; instead, most exhibit four distinct phases of migration, including a phase of retrograde movement toward the ventricle before migration to the cortical plate. These findings provide a comprehensive and new view of the dynamics of cortical neurogenesis and migration. 1097-6256 Journal Article}, Author = {Noctor, S. C. and Martinez-Cerdeno, V. and Ivic, L. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Nat Neurosci}, Keywords = {10 Development;F pdf}, Number = {2}, Organization = {Department of Neurology, Columbia University College of Physicians &Surgeons, 630 W. 168th Street, New York, New York 10032, USA.}, Pages = {136-44}, Pubmed = {14703572}, Title = {Cortical neurons arise in symmetric and asymmetric division zones and migrate through specific phases}, Uuid = {A13EE4C4-CF6F-4CC8-93FB-FA1D0D695968}, Volume = {7}, Year = {2004}, url = {papers/Noctor_NatNeurosci2004.pdf}} @article{Noctor:2001, Abstract = {The neocortex of the adult brain consists of neurons and glia that are generated by precursor cells of the embryonic ventricular zone. In general, glia are generated after neurons during development, but radial glia are an exception to this rule. Radial glia are generated before neurogenesis and guide neuronal migration. Radial glia are mitotically active throughout neurogenesis, and disappear or become astrocytes when neuronal migration is complete. Although the lineage relationships of cortical neurons and glia have been explored, the clonal relationship of radial glia to other cortical cells remains unknown. It has been suggested that radial glia may be neuronal precursors, but this has not been demonstrated in vivo. We have used a retroviral vector encoding enhanced green fluorescent protein to label precursor cells in vivo and have examined clones 1-3 days later using morphological, immunohistochemical and electrophysiological techniques. Here we show that clones consist of mitotic radial glia and postmitotic neurons, and that neurons migrate along clonally related radial glia. Time-lapse images show that proliferative radial glia generate neurons. Our results support the concept that a lineage relationship between neurons and proliferative radial glia may underlie the radial organization of neocortex.}, Author = {Noctor, S. C. and Flint, A. C. and Weissman, T. A. and Dammerman, R. S. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Nature}, Keywords = {Clone Cells;Cell Differentiation;Luminescent Proteins;Rats, Sprague-Dawley;Rats;Antigens, Differentiation/biosynthesis;Microscopy, Video;Neuroglia/*cytology;Animal;Neurons/*cytology;F;Mitosis;Neocortex/*cytology;Support, Non-U.S. Gov't;Cell Movement;Support, U.S. Gov't, P.H.S.}, Number = {6821}, Organization = {Department of Neurology, Columbia University College of Physicians &Surgeons, New York, New York 10032, USA.}, Pages = {714-20.}, Title = {Neurons derived from radial glial cells establish radial units in neocortex}, Uuid = {AE861032-71C2-11DA-A383-000D9346EC2A}, Volume = {409}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11217860}} @article{Nolte:1997, Abstract = {Epidermal growth factor (EGF) and its receptor are present in the central nervous system and modulate a variety of neural functions. Here we show that microglial cells, the brain-intrinsic macrophages, express the receptor for EGF and migrate in response to EGF. Transcripts encoding the EGF receptor could be detected in purified microglial cultures obtained from newborn mouse cortex. More specifically, cDNA fragments derived from EGF receptor mRNA could be amplified from 21\%of electrophysiologically characterized microglial cells by the use of a single-cell reverse transcription-polymerase chain reaction method. Expression of the protein was confirmed on rat microglia by flow cytometry. EGF dose-dependently stimulated chemotactic migration, as revealed with a microchemotaxis assay. The dose-response curve peaked-at 10 ng/ml EGF, reaching a 3-fold increase in migration over the unstimulated control; migration was about half of that induced by complement 5a (10 nM), a previously described microglial chemoattractant. Chequerboard analysis showed that EGF-induced motility was composed of both chemotaxis and chemokinesis. In contrast to its pronounced effect on cell motility, EGF (0.01-10 ng/ml) was not a mitotic signal for microglia, as shown by lack of bromodeoxyuridine incorporation. Acute and chronic pathological processes within the brain stimulate the synthesis and release of immunoregulators and growth factors (including EGF) that play a major role in the brain's response to injury. EGF may serve as a paracrine factor to direct microglial cells to the lesion site. Moreover, since EGF is secreted by activated microglia themselves in vivo, it may act as an autocrine modulator of microglial cell function.}, Author = {Nolte, C. and Kirchhoff, F. and Kettenmann, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Patch-Clamp Techniques;Mice, Inbred Strains;Receptor, Epidermal Growth Factor;Research Support, Non-U.S. Gov't;Alpha;Rats;Epidermal Growth Factor;Rats, Wistar;Cell Division;11 Glia;Microglia;Mitosis;Cells, Cultured;Animals;Chemotaxis;Mice;Cell Movement}, Medline = {97429473}, Month = {8}, Nlm_Id = {8918110}, Number = {8}, Organization = {Max Delbr{\"u}ck Centre for Molecular Medicine, Berlin, Germany.}, Pages = {1690-8}, Pubmed = {9283823}, Title = {Epidermal growth factor is a motility factor for microglial cells in vitro: evidence for EGF receptor expression}, Uuid = {472A3D1B-1BC8-454C-830A-4C46ED31416D}, Volume = {9}, Year = {1997}} @article{Nona:1998, Abstract = {In crushed goldfish optic nerve, regenerating axons cross the site of lesion within 10 days following injury. Some 30 days later, Schwann cells accumulate at the lesion, where they myelinate the new axons. In this study, we have used immunohistochemistry and electron microscopy to examine the cellular environment of the crush site prior to the establishment of Schwann cells in order to learn more about the early events that contribute to axonal regeneration. During the first week following injury, macrophages enter the site of lesion and efficiently phagocytose the debris. The infiltration of macrophages precedes the arrival of regenerating axons that abut and surround these phagocytes. Based on EM morphology and phagocytic capacity, macrophages of the type observed at the site of lesion are not present in the degenerating distal nerve segment, where debris clearance is shared between conventional microglia and astrocytes over a period of several weeks. During this period, axon bundles emerging distally from the injury zone become enwrapped by astrocyte processes, thereby re-establishing the characteristic fascicular cytoarchitecture of the optic nerve. The process of fasciculation also leads to the displacement of myelin debris to the margins of the fiber bundles, where it is trapped by the astrocytes. Our results suggest that the early robust appearance of macrophages at the lesion, and their effectiveness as phagocytes compared with the microglia distally, may contribute to the vigorous axonal regeneration across the crush, beyond which axons--excepting the pioneers--extend through newly formed debris-free channels delineated by astrocyte processes.}, Author = {Nona, S. N. and Thomlinson, A. M. and Stafford, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Goldfish;Nerve Regeneration;Microscopy, Electron;Not relevant;11 Glia;Macrophages;Optic Nerve;Nerve Crush;Support, Non-U.S. Gov't;Cell Movement;Animals;Phagocytosis;Axons}, Medline = {99382397}, Month = {11}, Nlm_Id = {0364620}, Number = {11}, Organization = {Neuroscience Group, Department of Optometry &Vision Sciences, UMIST, Manchester M60 1QD, UK.}, Pages = {791-803}, Pubmed = {10451426}, Title = {Temporary colonization of the site of lesion by macrophages is a prelude to the arrival of regenerated axons in injured goldfish optic nerve}, Uuid = {0F27F310-D697-45BB-8314-E055C5CE7BF4}, Volume = {27}, Year = {1998}} @article{Northcutt:1995, Abstract = {Cortical variation in mammals and other terrestrial vertebrates, re-examined by current comparative methodology (out-group analysis), indicates that separate lateral (olfactory), dorsal and medial (hippocampal) pallial or cortical formations arose with the origin of vertebrates. Although the exact origin of mammalian isocortex (so-called neocortex) is still disputed, it appears that the earliest mammals already had a six-layered isocortex with ten to 20 functional subdivisions. Among placental mammals, at least, isocortex has expanded numerous times, producing additional cortical subdivisions. Because these expansions were independent transformations of a simpler cortex, they produced subdivisions that are not homologous.}, Author = {Northcutt, R. G. and Kaas, J. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Visual Cortex;Visual Cortex/anatomy &histology/physiology;Cerebral Cortex/anatomy &histology/*physiology;Human;Mammals/*physiology;Mammals;Research Support, U.S. Gov't, P.H.S.;M;Evolution;review, tutorial;Support, U.S. Gov't, P.H.S.;Animals;Humans;Cerebral Cortex;review;*Evolution}, Medline = {96048677}, Month = {9}, nlmuniqueid = {7808616}, Number = {9}, Organization = {Neurobiology Unit, Scripps Institution of Oceanography, University of California, San Diego, La Jolla 92093, USA.}, Pages = {373-9}, Pii = {016622369593932N}, Pubmed = {7482801}, doi = {10.1016/0166-2236(95)93932-n}, Title = {The emergence and evolution of mammalian neocortex}, Uuid = {0BAEF209-062A-4194-85E6-4DA30F6A9908}, Volume = {18}, Year = {1995}, url = {papers/Northcutt_TrendsNeurosci1995.pdf}} @article{Nossal:2003, Abstract = {The immune system can recognize and produce antibodies to virtually any molecule in the Universe. This enormous diversity arises from the ingenious reshuffling of DNA sequences encoding components of the immune system. Immunology is an example of a field completely transformed during the past 50 years by the discovery of the structure of DNA and the emergence of DNA technologies that followed. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Nossal, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Nature}, Keywords = {DNA/chemistry/genetics/*metabolism;Vaccines, DNA/immunology;10 Development;Lymphocytes/immunology/metabolism;Human;Gene Rearrangement/*genetics;Antibody Diversity/*genetics;Animals;F pdf;Autoimmunity;Receptors, Antigen, T-Cell/*genetics;Lymphoma/genetics/immunology}, Number = {6921}, Organization = {Department of Pathology, The University of Melbourne, Victoria 3010, Australia.}, Pages = {440-4}, Pubmed = {12540919}, Title = {The double helix and immunology}, Uuid = {EF4596FE-3B14-42AA-B3FF-CD4FB8FED108}, Volume = {421}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12540919}} @article{Nosten-Bertrand:2008, Abstract = {Patients with Doublecortin (DCX) mutations have severe cortical malformations associated with mental retardation and epilepsy. Dcx knockout (KO) mice show no major isocortical abnormalities, but have discrete hippocampal defects. We questioned the functional consequences of these defects and report here that Dcx KO mice are hyperactive and exhibit spontaneous convulsive seizures. Changes in neuropeptide Y and calbindin expression, consistent with seizure occurrence, were detected in a large proportion of KO animals, and convulsants, including kainate and pentylenetetrazole, also induced seizures more readily in KO mice. We show that the dysplastic CA3 region in KO hippocampal slices generates sharp wave-like activities and possesses a lower threshold for epileptiform events. Video-EEG monitoring also demonstrated that spontaneous seizures were initiated in the hippocampus. Similarly, seizures in human patients mutated for DCX can show a primary involvement of the temporal lobe. In conclusion, seizures in Dcx KO mice are likely to be due to abnormal synaptic transmission involving heterotopic cells in the hippocampus and these mice may therefore provide a useful model to further study how lamination defects underlie the genesis of epileptiform activities.}, Author = {Nosten-Bertrand, Marika and Kappeler, Caroline and Dinocourt, C{\'e}line and Denis, C{\'e}cile and Germain, Johanne and Phan Dinh Tuy, Fran\c{c}oise and Verstraeten, Soraya and Alvarez, Chantal and M{\'e}tin, Christine and Chelly, Jamel and Giros, Bruno and Miles, Richard and Depaulis, Antoine and Francis, Fiona}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1932-6203}, Journal = {PLoS ONE}, Keywords = {Epilepsy;research support, non-u.s. gov't;Mice, Knockout;Hippocampus;Neuropeptides;Animals;Convulsants;Mice;Microtubule-Associated Proteins;24 Pubmed search results 2008}, Nlm_Id = {101285081}, Number = {6}, Organization = {INSERM, U513, Universit{\'e} Pierre et Marie Curie, Paris, France.}, Pages = {e2473}, Pmc = {PMC2429962}, Pubmed = {18575605}, Title = {Epilepsy in Dcx knockout mice associated with discrete lamination defects and enhanced excitability in the hippocampus}, Uuid = {3E817120-20BF-4C6F-A38D-5227F88C0697}, Volume = {3}, Year = {2008}, url = {papers/Nosten-Bertrand_PLoSONE2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0002473}} @article{Nottebohm:2002, Author = {Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;Cell Survival/physiology;Neurons/*cytology/physiology;Female;Regeneration/*physiology;Aging/physiology;A both;Cell Count;Animal;Memory/physiology;Brain/*cytology/growth &development;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Songbirds;Male;Research Design}, Number = {3}, Organization = {The Rockefeller University, Field Research Center, Millbrook, New York 12545, USA. nottebo\@mail.rockefeller.edu}, Pages = {624-8.}, Title = {Why are some neurons replaced in adult brain?}, Uuid = {6AE6B57F-4AAC-4EEE-9AC9-442EBAF62A9B}, Volume = {22}, Year = {2002}, url = {papers/Nottebohm_JNeurosci2002.pdf}} @article{Nottebohm:1994, Abstract = {The number of high vocal center (HVC) neurons labeled in adult male canaries by systemic injections of [3H]thymidine depended on season and survival time. This was true for HVC neurons projecting to the robust nucleus of the archistriatum and for other HVC neurons that could not be retrogradely filled from the robust nucleus of the archistriatum. Birds injected in October and killed 40 days later had twice as many labeled HVC neurons as birds injected in May and killed 40 days later. However, this difference became much larger (5 times) when the birds were allowed to survive for 4 months. Whereas more than half of the spring-born neurons disappeared between 40 days and 4 months, there was no reduction in the number of fall-born neurons present at the 4-month survival point. We infer that seasonal variables affect the life span of HVC neurons born in adulthood.}, Author = {Nottebohm, F. and O'Loughlin, B. and Gould, K. and Yohay, K. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Survival;Neurons/*cytology/physiology;Thymidine/metabolism;Aging/physiology;Animal;Periodicity;C abstr;Sex Maturation;Seasons;Male;Time Factors;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Canaries/*physiology;Vocalization, Animal/*physiology;Tritium;Autoradiography;Brain/*cytology/physiology}, Number = {17}, Organization = {Laboratory of Animal Behavior, Rockefeller University Field Research Center, Millbrook, NY 12545.}, Pages = {7849-53.}, Title = {The life span of new neurons in a song control nucleus of the adult canary brain depends on time of year when these cells are born}, Uuid = {15B8DD69-FD19-4D64-90D9-B29D82EB1445}, Volume = {91}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8058722}} @article{Novacek:1992, Abstract = {Recent palaeontological discoveries and the correspondence between molecular and morphological results provide fresh insight on the deep structure of mammalian phylogeny. This new wave of research, however, has yet to resolve some important issues. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Novacek, M. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Nature}, Keywords = {*Phylogeny;Mammals/classification/*genetics;Fossils;Evolution;N;Animals;19 Neocortical evolution}, Number = {6365}, Organization = {American Museum of Natural History, New York 10024.}, Pages = {121-5}, Pubmed = {1545862}, Title = {Mammalian phylogeny: shaking the tree}, Uuid = {BF935FC0-988A-4874-998A-0FDF23AE1F45}, Volume = {356}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1545862}} @article{Nowak:2006, Abstract = {Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.}, Author = {Nowak, Martin A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Helping Behavior;Mathematics;research support, non-u.s. gov't;Selection (Genetics);Community Networks;09 Evolutionary dynamics;Family;research support, u.s. gov't, non-p.h.s.;Cooperative Behavior;research support, n.i.h., extramural;Evolution;Game Theory;Humans;24 Pubmed search results 2008;review}, Month = {12}, Nlm_Id = {0404511}, Number = {5805}, Organization = {Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, and Department of Mathematics, Harvard University, Cambridge, MA 02138, USA. martin\_nowak\@harvard.edu}, Pages = {1560-3}, Pii = {314/5805/1560}, Pubmed = {17158317}, Title = {Five rules for the evolution of cooperation}, Uuid = {D5507917-F9E4-40D5-8D37-4084816E5E99}, Volume = {314}, Year = {2006}, url = {papers/Nowak_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1133755}} @article{Nowakowski:1989, Abstract = {A cumulative labelling protocol using 5-bromo-2'-deoxyuridine (BUdR) was followed to determine: (1) the growth fraction (i.e., the proportion of cells that comprise the proliferating population), (2) the length of the cell cycle, and (3) the length of the DNA-synthetic phase (S-phase) for proliferative cells in the dentate gyrus of the mouse. On postnatal day 20 (P20), C57BL/6J mice were injected with BUdR at two hour intervals for a total period of 12 hours. Animals were sacrificed at selected intervals, and the brains were processed for immunohistochemistry using a monoclonal antibody directed against single-stranded DNA containing BUdR. The numbers of BUdR-labelled and unlabelled cells in sections through the hilus of the dentate gyrus were counted. The number of BUdR-labelled cells increased linearly from an initial value of about 12\%of the total number of cells to a maximum value of just over 24\%of the total. These findings indicate that, at P20, a maximum of 24.2 +/- 1.2\%of the cells in the dentate hilus are part of the proliferating population. The calculated length of the cell cycle of the cells comprising the intrahilar proliferative zone was estimated to be 16.1 +/- 0.8 h. The length of the S-phase was estimated at 8.0 +/- 0.4 h. In addition, mathematical analysis, using one and two population models, indicates that over 90\%of the proliferating cells in the dentate hilus at this age comprise a single population at least in terms of the lengths of the cell cycle and the S-phase.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Nowakowski, R. S. and Lewin, S. B. and Miller, M. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:37 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {21 Epilepsy;01 Adult neurogenesis general;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;21 Neurophysiology;Immunohistochemistry;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Time Factors;Cell Cycle;Animals;Interphase;Bromodeoxyuridine;Mice, Inbred Strains;Mice}, Medline = {89310645}, Month = {6}, Nlm_Id = {0364620}, Number = {3}, Organization = {Department of Anatomy, UMDNJ-Robert Wood Johnson Medical School, Piscataway 08854.}, Pages = {311-8}, Pubmed = {2746304}, Title = {Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population}, Uuid = {F1896EB1-429E-11DB-A5D2-000D9346EC2A}, Volume = {18}, Year = {1989}} @article{Nowakowski:2006, Author = {Nowakowski, Richard S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;comment;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {33}, Organization = {Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ 08873, USA. rsn\@umdnj.edu}, Pages = {12219-20}, Pii = {0605605103}, Pubmed = {16894140}, Title = {Stable neuron numbers from cradle to grave}, Uuid = {050E72AD-6EB4-4569-BC73-56865C878E9B}, Volume = {103}, Year = {2006}, url = {papers/Nowakowski_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0605605103}} @article{Nowakowski:2000, Author = {Nowakowski, R. S. and Hayes, N. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Macaca;01 Adult neurogenesis general;Immunohistochemistry;Cell Division;Neocortex;DNA Repair;Biological Markers;Cell Death;comment;DNA Replication;Animals;Bromodeoxyuridine;Cell Movement;Brain;Neurons}, Medline = {20266944}, Month = {5}, Nlm_Id = {0404511}, Number = {5467}, Organization = {Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08854, USA. rsn\@umdnj.edu}, Pages = {771}, Pubmed = {10809639}, Title = {New neurons: extraordinary evidence or extraordinary conclusion?}, Uuid = {41C0910E-D38B-11D9-A0E9-000D9346EC2A}, Volume = {288}, Year = {2000}, url = {papers/Nowakowski_Science2000.pdf}} @article{Nuriya:2006, Abstract = {Dendritic spines mediate most excitatory inputs in the brain. Although it is clear that spines compartmentalize calcium, it is still unknown what role, if any, they play in integrating synaptic inputs. To investigate the electrical function of spines directly, we used second harmonic generation (SHG) imaging of membrane potential in pyramidal neurons from hippocampal cultures and neocortical brain slices. With FM 4-64 as an intracellular SHG chromophore, we imaged membrane potential in the soma, dendritic branches, and spines. The SHG response to voltage was linear and seemed based on an electro-optic mechanism. The SHG sensitivity of the chromophore in spines was similar to that of the parent dendritic shaft and the soma. Backpropagation of somatic action potentials generated SHG signals at spines with similar amplitude and kinetics to somatic ones. Our optical measurements of membrane potential from spines demonstrate directly that backpropagating action potentials invade the spines.}, Author = {Nuriya, Mutsuo and Jiang, Jiang and Nemet, Boaz and Eisenthal, Kenneth B. and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Animals;In Vitro;Microscopy, Confocal;Research Support, U.S. Gov't, Non-P.H.S.;Patch-Clamp Techniques;Dendritic Spines;Pyramidal Cells;Mice, Inbred C57BL;21 Calcium imaging;Action Potentials;21 Neurophysiology;Membrane Potentials;Quaternary Ammonium Compounds;Mice;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Pyridinium Compounds;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {7505876}, Number = {3}, Organization = {Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {786-90}, Pii = {0510092103}, Pubmed = {16407122}, Title = {Imaging membrane potential in dendritic spines}, Uuid = {8F3F4486-96D1-44EB-A236-2F1A1532FE38}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0510092103}} @article{Nusser:2001, Abstract = {Synchronized neural activity is believed to be essential for many CNS functions, including neuronal development, sensory perception, and memory formation. In several brain areas GABA(A) receptor-mediated synaptic inhibition is thought to be important for the generation of synchronous network activity. We have used GABA(A) receptor beta3 subunit deficient mice (beta3-/-) to study the role of GABAergic inhibition in the generation of network oscillations in the olfactory bulb (OB) and to reveal the role of such oscillations in olfaction. The expression of functional GABA(A) receptors was drastically reduced (>93\%) in beta3-/- granule cells, the local inhibitory interneurons of the OB. This was revealed by a large reduction of muscimol-evoked whole- cell current and the total current mediated by spontaneous, miniature inhibitory postsynaptic currents (mIPSCs). In beta3-/- mitral/tufted cells (principal cells), there was a two-fold increase in mIPSC amplitudes without any significant change in their kinetics or frequency. In parallel with the altered inhibition, there was a significant increase in the amplitude of theta (80\%increase) and gamma (178\%increase) frequency oscillations in beta3-/- OBs recorded in vivo from freely moving mice. In odor discrimination tests, we found beta3-/- mice to be initially the same as, but better with experience than beta3+/+ mice in distinguishing closely related monomolecular alcohols. However, beta3-/- mice were initially better and then worse with practice than control mice in distinguishing closely related mixtures of alcohols. Our results indicate that the disruption of GABA(A) receptor-mediated synaptic inhibition of GABAergic interneurons and the augmentation of IPSCs in principal cells result in increased network oscillations in the OB with complex effects on olfactory discrimination, which can be explained by an increase in the size or effective power of oscillating neural cell assemblies among the mitral cells of beta3-/- mice.}, Author = {Nusser, Z. and Kay, L. M. and Laurent, G. and Homanics, G. E. and Mody, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {J Neurophysiol}, Keywords = {Synaptic Transmission/drug effects/physiology;13 Olfactory bulb anatomy;Electrophysiology;Discrimination (Psychology)/physiology;Animal;Motor Activity/physiology;Nerve Net/*physiology;gamma-Aminobutyric Acid/*physiology;Odors;Olfactory Bulb/cytology/*physiology;Receptors, GABA-A/genetics/*physiology;Support, Non-U.S. Gov't;Mice, Knockout;Smell/genetics/*physiology;Support, U.S. Gov't, P.H.S.;I pdf;Mice;Immunohistochemistry;Interneurons/*physiology}, Number = {6}, Organization = {Department of Neurology, UCLA School of Medicine, Los Angeles 90095- 1769, California, USA. nusser\@koki.hu}, Pages = {2823-33.}, Title = {Disruption of GABA(A) receptors on GABAergic interneurons leads to increased oscillatory power in the olfactory bulb network}, Uuid = {63581941-F70D-483C-B0EC-DE192C5BCE23}, Volume = {86}, Year = {2001}, url = {papers/Nusser_JNeurophysiol2001}} @article{Nygren:2006, Abstract = {BACKGROUND AND PURPOSE: Cells proliferate continuously in the adult mammalian brain, and in rodents, cell genesis is affected by housing conditions and brain injury. Increase in neurogenesis after brain ischemia has been postulated to be linked to functional recovery after stroke. Housing rodents in an enriched environment improves motor function after stroke injury. We have investigated whether changes in cell genesis can explain the beneficial effects of an enriched environment. METHODS: Intact mice and mice subjected to transient occlusion of the middle cerebral artery were exposed to an enriched environment for 1 month. Bromodeoxyuridine was injected daily to label proliferating cells during the first postischemic week. Newborn cells were analyzed immunohistochemically after 4 weeks. RESULTS: The enriched environment increased neurogenesis in the dentate gyrus in both intact and stroke-injured animals. An increased number of newborn cells was found in the subventricular zone of stroke-injured mice, but not in injured mice exposed to an enriched environment. Also, the number of newborn astrocytes (BrdU+/S-100beta+ cells), neuroblasts (dcx+ cells), and reactive astrocytes (vimentin mRNA) in the striatum ipsilateral to the ischemic injury was markedly attenuated and new adult neurons (BrdU+/NeuN+) were not found. The enriched environment did not affect infarct size or mortality. CONCLUSIONS: An enriched environment after experimental stroke increased neurogenesis in the hippocampus, whereas there was a decreased cell genesis and migration of neuroblasts and newborn astrocytes in the striatum.}, Author = {Nygren, Josefine and Wieloch, Tadeusz and Pesic, Jelena and Brundin, Patrik and Deierborg, Tomas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1524-4628}, Journal = {Stroke}, Keywords = {Male;Mice;Brain Ischemia;Cell Differentiation;research support, non-u.s. gov't ;Environment;Mice, Inbred C57BL;Stem Cells;Corpus Striatum;Cell Count;Animals;comparative study ;24 Pubmed search results 2008;Cell Movement;Cerebral Ventricles}, Month = {11}, Nlm_Id = {0235266}, Number = {11}, Organization = {Experimental Brain Research, Wallenberg Neuroscience Center, Lund University, Lund, Sweden.}, Pages = {2824-9}, Pii = {01.STR.0000244769.39952.90}, Pubmed = {17008628}, Title = {Enriched environment attenuates cell genesis in subventricular zone after focal ischemia in mice and decreases migration of newborn cells to the striatum}, Uuid = {1A7761B1-F051-40C3-AEE6-865C0870EC84}, Volume = {37}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.STR.0000244769.39952.90}} @article{ONeill:2008, Abstract = {The hippocampus is thought to be involved in episodic memory formation by reactivating traces of waking experience during sleep. Indeed, the joint firing of spatially tuned pyramidal cells encoding nearby places recur during sleep. We found that the sleep cofiring of rat CA1 pyramidal cells encoding similar places increased relative to the sleep session before exploration. This cofiring increase depended on the number of times that cells fired together with short latencies (<50 ms) during exploration, and was strongest between cells representing the most visited places. This is indicative of a Hebbian learning rule in which changes in firing associations between cells are determined by the number of waking coincident firing events. In contrast, cells encoding different locations reduced their cofiring in proportion to the number of times that they fired independently. Together these data indicate that reactivated patterns are shaped by both positive and negative changes in cofiring, which are determined by recent behavior.}, Author = {O'Neill, Joseph and Senior, Timothy J. and Allen, Kevin and Huxter, John R. and Csicsvari, Jozsef}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9809671}, Number = {2}, Organization = {Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3TH, UK.}, Pages = {209-15}, Pii = {nn2037}, Pubmed = {18193040}, Title = {Reactivation of experience-dependent cell assembly patterns in the hippocampus}, Uuid = {E7D0A4B6-B1B0-40D7-8E9E-A2824F59525A}, Volume = {11}, Year = {2008}, url = {papers/O'Neill_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn2037}} @article{ORourke:1996, Author = {O'Rourke, N. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Neuron}, Keywords = {Neurons/*physiology;02 Adult neurogenesis migration;Animal;Olfactory Bulb/*physiology;B abstr;Neural Pathways/*anatomy &histology}, Number = {6}, Organization = {Department of Biological Sciences, Stanford University, California 94305, USA.}, Pages = {1061-4.}, Title = {Neuronal chain gangs: homotypic contacts support migration into the olfactory bulb}, Uuid = {99643B5B-1AA9-4152-BE60-9727AB841FC2}, Volume = {16}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8663980}} @article{Oberto:2001, Abstract = {ErbB-4 is expressed by the periglomerular and the mitral/tufted cells of the adult mouse olfactory bulb (OB) and in the present work we tested whether this expression is regulated by the olfactory nerve input to the OB. Reversible zinc sulphate lesions of the olfactory mucosa were made in adult mice and the deafferented OB analysed by immunohistochemistry, Western blotting and semiquantitative RT-PCR. Following deafferentation, the expression of erbB-4, erbB-2 and neuregulin-1 (NRG-1) mRNAs in the OB was altered. At early stages (7-14 days) after lesion the levels of expression of olfactory marker protein (OMP), tyrosine hydroxylase (TH), erbB-4 and NRG-1 mRNAs were decreased, whilst expression of erbB-2 increased and that of NRG-2 was not significantly altered. We observed at least two distinct time courses for these expression changes. The lowest amounts of mRNA for erbB-4 and NRG-1 were observed at day 7 after lesion, whilst mRNAs for TH and OMP were lowest at day 14. At day 28 after the lesion, when olfactory receptor neuron axons had reinnervated the olfactory bulb, the expression levels of OMP, TH, erbB-2, erbB-4 and NRG-1 were identical to control values. These results indicate that the expression of erbB-4 mRNA and protein in periglomerular and mitral cells is controlled by peripheral olfactory innervation. The tight correlation in NRG-1 and erbB-4 expression levels also suggests a possible functional link that deserves further exploration.}, Author = {Oberto, M. and Soncin, I. and Bovolin, P. and Voyron, S. and De Bortoli, M. and Dati, C. and Fasolo, A. and Perroteau, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Eur J Neurosci}, Keywords = {I pdf;13 Olfactory bulb anatomy}, Number = {3}, Organization = {Department of Human and Animal Biology, University of Turin, via Accademia Albertina 13, Torino10123, Italy.}, Pages = {513-21.}, Title = {ErbB-4 and neuregulin expression in the adult mouse olfactory bulb after peripheral denervation}, Uuid = {E22B0764-ADA8-4398-BCB0-E6C9D85F30C5}, Volume = {14}, Year = {2001}, url = {papers/Oberto_EurJNeurosci2001}} @article{Odenwald:2005, Abstract = {One of the longstanding goals of neurobiologists is to describe, in molecular terms, how a neural progenitor cell (NPC) can generate an ordered series of uniquely fated neurons and glia. Recent studies reveal that many, or all, neural-subtype identities can be linked to sequentially changing regulatory programs within NPCs. Two new studies, in this issue of Developmental Cell, provide novel insights into the molecular details of how Drosophila NPCs transition from one offspring identity program to the next.}, Author = {Odenwald, Ward F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1534-5807}, Journal = {Dev Cell}, Keywords = {10 Development}, Month = {2}, Nlm_Id = {101120028}, Number = {2}, Pages = {133-4}, Pii = {S1534-5807(05)00007-9}, Pubmed = {15691753}, Title = {Changing fates on the road to neuronal diversity}, Uuid = {A5597378-95F8-4D4B-955F-9562B5BFC8F5}, Volume = {8}, Year = {2005}, url = {papers/Odenwald_DevCell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devcel.2005.01.005}} @article{Oehmichen:1982, Abstract = {According to recent submicroscopic, cytokinetics, and functional (particularly cytoimmunologic) investigations, no relationship exists between "resting" microglia (the small argyrophilic cells appearing in undamaged brain tissue, first described by Rio Hortega) and "reactive" microglia (the argyrophilic cells appearing under pathologic conditions). While "resting" microglia are apparently cells of neuro-ectodermal origin, all observations tend to indicate that "reactive" microglia are derived from extravasated blood monocytes and should be called brain macrophages. In the intact brain parenchyma, no macrophages are demonstrable. Free subarachnoidal cells in the cerebrospinal fluid (CSF), perivascular cells, and epiplexus and/or supraependymal cells in the CSF-containing spaces of the normal central nervous system are cells of the mononuclear phagocyte system and must be considered as CSF macrophages. According to rough estimates, the normal adult central nervous system contains a maximum of 280,000 CSF macrophages.}, Author = {Oehmichen, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0171-2985}, Journal = {Immunobiology}, Keywords = {Rabbits;Cell Differentiation;Animals;Phagocytosis;Monocytes;Macrophages;Bone Marrow Transplantation;Mitosis;Brain;review;Mammals;Wounds, Stab;11 Glia;Phagocytes;Brain Injuries;Cell Adhesion;Cerebrospinal Fluid;Receptors, Fc;Mice}, Medline = {82238040}, Month = {4}, Nlm_Id = {8002742}, Number = {3-4}, Pages = {246-54}, Pubmed = {7047372}, Title = {Are resting and/or reactive microglia macrophages?}, Uuid = {43CFF1E2-9352-48B7-AC5E-126061607A41}, Volume = {161}, Year = {1982}} @article{Ogle:2004, Abstract = {Human cells can fuse with damaged or diseased somatic cells in vivo. Whether human cells fuse in vivo in the absence of disease and with cells of disparate species is unknown. Such a question is of current interest because blood exchanges between species through direct physical contact, via insect vectors or parasitism, are thought to underlie the transmission of zoonotic agents. In a model of human-pig chimerism, we show that some human hematopoietic stem cells engrafted in pigs contain both human and porcine chromosomal DNA. These hybrid cells divide, express human and porcine proteins, and contribute to porcine nonhematopoietic tissues. In addition, the hybrid cells contain porcine endogenous retroviral DNA sequences and are able to transmit this virus to uninfected human cells in vitro. Thus, spontaneous fusion can occur in vivo between the cells of disparate species and in the absence of disease. The ability of these cell hybrids to acquire and transmit retroviral elements together with their ability to integrate into tissues could explain genetic recombination and generation of novel pathogens. * differentiation * fusion * retrovirus}, Author = {Ogle, Brenda M. and Butters, Kim A. and Plummer, Timothy B. and Ring, Kevin R. and Knudsen, Bruce E. and Litzow, Mark R. and Cascalho, Marilia and Platt, Jeffrey L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {Cell Differentiation;Transplantation Chimera;Genetic Markers;Cell Line;24 Pubmed search results 2008;Ploidies;Organ Specificity;DNA, Viral;Kidney;Animals;Endogenous Retroviruses;Herpesvirus 4, Human;15 Retrovirus mechanism;Swine;Blood Transfusion, Intrauterine;Hybrid Cells;Hematopoietic Stem Cells;Chromosome Banding;Species Specificity;Skin;Transplantation, Heterologous;Hematopoietic Stem Cell Transplantation;15 ERVs retroelements;Comparative Study;Graft Survival;Retroviridae Infections;Cell Lineage;Genes, pol;Fibroblasts;B-Lymphocytes;Cell Line, Transformed;Cell Fusion;Humans}, Month = {3}, Nlm_Id = {8804484}, Number = {3}, Organization = {Transplantation Biology, Mayo Clinic, Rochester, Minnesota 55905, USA.}, Pages = {548-50}, Pii = {03-0962fje}, Pubmed = {14715691}, Title = {Spontaneous fusion of cells between species yields transdifferentiation and retroviral transfer in vivo}, Uuid = {6A461CA7-71DF-494C-B3D6-1E8697EE059F}, Volume = {18}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.03-0962fje}} @article{Ogle:2005, Abstract = {Until recently, cells were thought to be integral and discrete components of tissues, and their state was determined by cell differentiation. However, under some conditions, stem cells or their progeny can fuse with cells of other types, mixing cytoplasmic and even genetic material of different (heterotypic) origins. The fusion of heterotypic cells could be of central importance for development, repair of tissues and the pathogenesis of disease.}, Author = {Ogle, Brenda M. and Cascalho, Marilia and Platt, Jeffrey L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1471-0072}, Journal = {Nat Rev Mol Cell Biol}, Keywords = {Aging;Models, Biological;Cell Differentiation;Cell Fusion;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Research Support, N.I.H., Extramural;Humans;Animals;24 Pubmed search results 2008;review}, Month = {7}, Nlm_Id = {100962782}, Number = {7}, Organization = {Transplantation Biology and the Department of Physiology, Mayo Clinic, Rochester, Minnesota 55905, USA.}, Pages = {567-75}, Pii = {nrm1678}, Pubmed = {15957005}, Title = {Biological implications of cell fusion}, Uuid = {C7E0D578-A523-4852-83B9-15723F07EE35}, Volume = {6}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrm1678}} @article{Ogura:1995, Abstract = {Superfusion of guinea pig papillary muscles with Tyrode's solution that contained 0.3\%to 10\%dimethyl sulfoxide (DMSO) caused a small hyperpolarization, a prolongation of the action potential (e.g., 4\%, 15\%and 33\%prolongation with 1\%, 5\%and 10\%DMSO, respectively) and a reduction (100 microm). Consequently, the purity of functional domains and the precision of the borders between them could not be resolved. Here, we labelled thousands of neurons of the visual cortex with a calcium-sensitive indicator in vivo. We then imaged the activity of neuronal populations at single-cell resolution with two-photon microscopy up to a depth of 400 microm. In rat primary visual cortex, neurons had robust orientation selectivity but there was no discernible local structure; neighbouring neurons often responded to different orientations. In area 18 of cat visual cortex, functional maps were organized at a fine scale. Neurons with opposite preferences for stimulus direction were segregated with extraordinary spatial precision in three dimensions, with columnar borders one to two cells wide. These results indicate that cortical maps can be built with single-cell precision.}, Author = {Ohki, Kenichi and Chung, Sooyoung and Ch'ng, Yeang H. and Kara, Prakash and Reid, R. Clay}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {18 Classic Neuroanatomy Physiology;Visual Cortex;Photic Stimulation;Research Support, Non-U.S. Gov't;Cats;Rats, Long-Evans;Rats;Research Support, U.S. Gov't, P.H.S.;Analysis of Variance;Electrophysiology;Calcium Signaling;Animals;24 Pubmed search results 2008;Neurons;23 Technique}, Month = {2}, Nlm_Id = {0410462}, Number = {7026}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {597-603}, Pii = {nature03274}, Pubmed = {15660108}, Title = {Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex}, Uuid = {1DCBC0BF-372C-4977-AD87-46415207E6FA}, Volume = {433}, Year = {2005}, url = {papers/Ohki_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03274}} @article{Ohki:2006, Abstract = {In the visual cortex of higher mammals, neurons are arranged across the cortical surface in an orderly map of preferred stimulus orientations. This map contains 'orientation pinwheels', structures that are arranged like the spokes of a wheel such that orientation changes continuously around a centre. Conventional optical imaging first demonstrated these pinwheels, but the technique lacked the spatial resolution to determine the response properties and arrangement of cells near pinwheel centres. Electrophysiological recordings later demonstrated sharply selective neurons near pinwheel centres, but it remained unclear whether they were arranged randomly or in an orderly fashion. Here we use two-photon calcium imaging in vivo to determine the microstructure of pinwheel centres in cat visual cortex with single-cell resolution. We find that pinwheel centres are highly ordered: neurons selective to different orientations are clearly segregated even in the very centre. Thus, pinwheel centres truly represent singularities in the cortical map. This highly ordered arrangement at the level of single cells suggests great precision in the development of cortical circuits underlying orientation selectivity.}, Author = {Ohki, Kenichi and Chung, Sooyoung and Kara, Prakash and H{\"u}bener, Mark and Bonhoeffer, Tobias and Reid, R. Clay}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Visual Cortex;Photic Stimulation;21 Neurophysiology;Cats;research support, non-u.s. gov't ;Models, Neurological;research support, u.s. gov't, non-p.h.s. ;Electrophysiology;Morphogenesis;Animals;24 Pubmed search results 2008;Neurons}, Month = {8}, Nlm_Id = {0410462}, Number = {7105}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {925-8}, Pii = {nature05019}, Pubmed = {16906137}, Title = {Highly ordered arrangement of single neurons in orientation pinwheels}, Uuid = {5147DCE8-8123-4FE3-B780-0FE01AD89DFA}, Volume = {442}, Year = {2006}, url = {papers/Ohki_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05019}} @article{Ohnuma:2003, Abstract = {For a long time, it has been understood that neurogenesis is linked to proliferation and thus to the cell cycle. Recently, the gears that mediate this linkage have become accessible to molecular investigation. This review describes some of the progress that has been made in understanding how the molecular machinery of the cell cycle is used in the processes of size regulation in the brain, histogenesis, neuronal differentiation, and the maintenance of stem cells. 0896-6273 Journal Article Review Review, Tutorial}, Author = {Ohnuma, S. and Harris, W. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Neuron}, Keywords = {Neurons/*cytology/*physiology;10 Development;Human;Cell Cycle/*physiology;Cell Differentiation/physiology;Stem Cells/cytology/physiology;Support, Non-U.S. Gov't;Animals;F pdf}, Number = {2}, Organization = {Department of Oncology, The Hutchison/MRC Research Centre, University of Cambridge, Hills Road, Cambridge CB2 2XZ, United Kingdom. so218\@cam.ac.uk}, Pages = {199-208}, Pubmed = {14556704}, Title = {Neurogenesis and the cell cycle}, Uuid = {6E64FCE9-3254-43C7-B893-3C710B7F5A01}, Volume = {40}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14556704}} @article{Ohori:2006, Abstract = {Neurons and oligodendrocytes are highly vulnerable to various insults, and their spontaneous replacement occurs to only a limited extent after damage in the adult spinal cord. The environment of injured tissue is thus thought to restrict the regenerative capacity of endogenous neural stem/progenitor cells; strategies for overcoming such restrictions remain to be developed. Here, we combined growth factor treatment and genetic manipulation to stimulate neurogenesis and oligodendrogenesis by endogenous progenitors in vivo. The recombinant retrovirus pMXIG, which was designed to coexpress green fluorescent proteins (GFPs) and a neurogenic/gliogenic transcription factor, was directly injected into the injured spinal cord parenchyma to manipulate proliferative cells in situ. We found that cells expressing Olig2, Nkx2.2, and NG2 were enriched among virus-infected, GFP-positive (GFP+) cells. Moreover, a fraction of GFP+ cells formed neurospheres and differentiated into neurons, astrocytes, and oligodendrocytes in vitro, demonstrating that GFP retroviruses indeed infected endogenous neural progenitors in vivo. Neuronal differentiation of control virus-infected cells did not occur at a detectable level in the injured spinal cord. We found, however, that direct administration of fibroblast growth factor 2 and epidermal growth factor into lesioned tissue could induce a significant fraction of GFP-labeled cells to express immature neuronal markers. Moreover, retrovirus-mediated overexpression of the basic helix-loop-helix transcription factors Neurogenin2 and Mash1, together with growth factor treatment, enhanced the production and maturation of new neurons and oligodendrocytes, respectively. These results demonstrate that endogenous neural progenitors can be manipulated to replace neurons and oligodendrocytes lost to insults in the injured spinal cord.}, Author = {Ohori, Yasuo and Yamamoto, Shin-ichi and Nagao, Motoshi and Sugimori, Michiya and Yamamoto, Naoya and Nakamura, Kozo and Nakafuku, Masato}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Animals;Transcription Factors;Cells, Cultured;Treatment Outcome;Rats;Proteoglycans;Basic Helix-Loop-Helix Transcription Factors;Oligodendroglia;Homeodomain Proteins;Rats, Sprague-Dawley;Retroviridae;Disease Models, Animal;Fibroblast Growth Factor 2;Genetic Vectors;research support, non-u.s. gov't;Green Fluorescent Proteins;Spinal Cord;Antigens;Gene Therapy;Intercellular Signaling Peptides and Proteins;Neurons;Epidermal Growth Factor;Spinal Cord Injuries;24 Pubmed search results 2008;Stem Cells;Nerve Tissue Proteins}, Month = {11}, Nlm_Id = {8102140}, Number = {46}, Organization = {Division of Developmental Biology, Cincinnati Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.}, Pages = {11948-60}, Pii = {26/46/11948}, Pubmed = {17108169}, Title = {Growth factor treatment and genetic manipulation stimulate neurogenesis and oligodendrogenesis by endogenous neural progenitors in the injured adult spinal cord}, Uuid = {26A84389-39E2-406B-85B4-14425E058AC8}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3127-06.2006}} @article{Ohsawa:2004, Abstract = {Ionized calcium binding adaptor molecule 1 (Iba1) is a microglia/macrophage-specific calcium-binding protein. Iba1 has the actin-bundling activity and participates in membrane ruffling and phagocytosis in activated microglia. In order to understand the Iba1-related intracellular signalling pathway in greater detail, we employed a yeast two-hybrid screen to isolate an Iba1-interacting molecule and identified another actin-bundling protein, L-fimbrin. In response to stimulation, L-fimbrin accumulated and co-localized with Iba1 in membrane ruffles induced by M-CSF-stimulation and phagocytic cups formed by IgG-opsonized beads in microglial cell line MG5. L-fimbrin was shown to associate with Iba1 in cell lysate of COS-7 expressing L-fimbrin and Iba1. By using purified proteins, direct binding of Iba1 to L-fimbrin was demonstrated by immunoprecipitation, glutathione S-transferase pull-down assays and ligand overlay assays. The binding of Iba1 was also found to increase the actin-bundling activity of L-fimbrin. These results indicate that Iba1 forms complexes with L-fimbrin in membrane ruffles and phagocytic cups, and suggest that Iba1 co-operates with L-fimbrin in modulating actin reorganization to facilitate cell migration and phagocytosis by microglia.}, Author = {Ohsawa, Keiko and Imai, Yoshinori and Sasaki, Yo and Kohsaka, Shinichi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Microinjections;Immunohistochemistry;Luminescent Proteins;Calcium-Binding Proteins;Brain;Cells, Cultured;Animals;Egtazic Acid;Proteins;Axotomy;Two-Hybrid System Techniques;11 Glia;Plasmids;Mutation;Not relevant;Membrane Glycoproteins;Comparative Study;Blotting, Western;Amino Acid Sequence;Facial Nerve;COS Cells;Calcium;Rats;Time Factors;Dose-Response Relationship, Drug;Microglia;Macrophage Colony-Stimulating Factor;Actins;Immunoglobulin G;Support, Non-U.S. Gov't;Recombinant Proteins;Rats, Wistar;Precipitin Tests;Cercopithecus aethiops}, Month = {2}, Nlm_Id = {2985190R}, Number = {4}, Organization = {Department of Neurochemistry, National Institute of Neuroscience, Tokyo, Japan. kohsaka\@ncnp.go.jp}, Pages = {844-56}, Pii = {2213}, Pubmed = {14756805}, Title = {Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity}, Uuid = {7E23523B-2635-4B90-BAFA-30376629DBFC}, Volume = {88}, Year = {2004}} @article{Ohshima:1996, Abstract = {Although cyclin-dependent kinase 5 (Cdk5) is closely related to other cyclin-dependent kinases, its kinase activity is detected only in the postmitotic neurons. Cdk5 expression and kinase activity are correlated with the extent of differentiation of neuronal cells in developing brain. Cdk5 purified from nervous tissue phosphorylates neuronal cytoskeletal proteins including neurofilament proteins and microtubule-associated protein tau in vitro. These findings indicate that Cdk5 may have unique functions in neuronal cells, especially in the regulation of phosphorylation of cytoskeletal molecules. We report here generation of Cdk5(-/-) mice through gene targeting and their phenotypic analysis. Cdk5(-/-) mice exhibit unique lesions in the central nervous system associated with perinatal mortality. The brains of Cdk5(-/-) mice lack cortical laminar structure and cerebellar foliation. In addition, the large neurons in the brain stem and in the spinal cord show chromatolytic changes with accumulation of neurofilament immunoreactivity. These findings indicate that Cdk5 is an important molecule for brain development and neuronal differentiation and also suggest that Cdk5 may play critical roles in neuronal cytoskeleton structure and organization.}, Author = {Ohshima, T. and Ward, J. M. and Huh, C. G. and Longenecker, G. and Veeranna and Pant, H. C. and Brady, R. O. and Martin, L. J. and Kulkarni, A. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Phosphorylation;24 Pubmed search results 2008;10 Development;Mice, Knockout;Cell Compartmentation;Genes, Lethal;Cyclin-Dependent Kinases;Neurofilament Proteins;Cyclins;Cerebellum;Protein-Serine-Threonine Kinases;10 genetics malformation;Animals;Cyclin-Dependent Kinase 5;Cerebral Cortex;Mice;Axons}, Month = {10}, Nlm_Id = {7505876}, Number = {20}, Organization = {National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.}, Pages = {11173-8}, Pubmed = {8855328}, Title = {Targeted disruption of the cyclin-dependent kinase 5 gene results in abnormal corticogenesis, neuronal pathology and perinatal death}, Uuid = {4ECB21B9-CA24-417C-916F-7721E7188D06}, Volume = {93}, Year = {1996}} @article{Ohtsuki:2006, Abstract = {A fundamental aspect of all biological systems is cooperation. Cooperative interactions are required for many levels of biological organization ranging from single cells to groups of animals. Human society is based to a large extent on mechanisms that promote cooperation. It is well known that in unstructured populations, natural selection favours defectors over cooperators. There is much current interest, however, in studying evolutionary games in structured populations and on graphs. These efforts recognize the fact that who-meets-whom is not random, but determined by spatial relationships or social networks. Here we describe a surprisingly simple rule that is a good approximation for all graphs that we have analysed, including cycles, spatial lattices, random regular graphs, random graphs and scale-free networks: natural selection favours cooperation, if the benefit of the altruistic act, b, divided by the cost, c, exceeds the average number of neighbours, k, which means b/c > k. In this case, cooperation can evolve as a consequence of 'social viscosity' even in the absence of reputation effects or strategic complexity.}, Author = {Ohtsuki, Hisashi and Hauert, Christoph and Lieberman, Erez and Nowak, Martin A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Altruism;20 Networks;Models, Biological;research support, non-u.s. gov't;Selection (Genetics);09 Evolutionary dynamics;Social Support;Cooperative Behavior;Evolution;Costs and Cost Analysis;Game Theory;Animals;Humans;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0410462}, Number = {7092}, Organization = {Department of Biology, Kyushu University, Fukuoka 812-8581, Japan.}, Pages = {502-5}, Pii = {nature04605}, Pubmed = {16724065}, Title = {A simple rule for the evolution of cooperation on graphs and social networks}, Uuid = {C3D00447-D136-438D-A81C-F52425D3DD1E}, Volume = {441}, Year = {2006}, url = {papers/Ohtsuki_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04605}} @article{Ojima:2004, Abstract = {Recent studies have shown that bone marrow (BM) cells, including the BM side population (BM-SP) cells that enrich hematopoietic stem cells (HSCs), are incorporated into skeletal muscle during regeneration, but it is not clear how and what kinds of BM cells contribute to muscle fiber regeneration. We found that a large number of SP cells migrated from BM to muscles following injury in BM-transplanted mice. These BM-derived SP cells in regenerating muscles expressed different surface markers from those of HSCs and could not reconstitute the mouse blood system. BM-derived SP/Mac-1(low) cells increased in number in regenerating muscles following injury. Importantly, our co-culture studies with activated satellite cells revealed that this fraction carried significant potential for myogenic differentiation. By contrast, mature inflammatory (Mac-1(high)) cells showed negligible myogenic activities. Further, these BM-derived SP/Mac-1(low) cells gave rise to mononucleate myocytes, indicating that their myogenesis was not caused by stochastic fusion with host myogenic cells, although they required cell-to-cell contact with myogenic cells for muscle differentiation. Taken together, our data suggest that neither HSCs nor mature inflammatory cells, but Mac-1(low) early myeloid cells in the BM-derived SP fraction, play an important role in regenerating skeletal muscles.}, Author = {Ojima, Koichi and Uezumi, Akiyoshi and Miyoshi, Hiroyuki and Masuda, Satoru and Morita, Yohei and Fukase, Akiko and Hattori, Akihito and Nakauchi, Hiromitsu and Miyagoe-Suzuki, Yuko and Takeda, Shin'ichi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0006-291X}, Journal = {Biochem Biophys Res Commun}, Keywords = {Cell Differentiation;Animals;Models, Biological;Cell Movement;Mice, Transgenic;Myeloid Cells;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Bone Marrow Cells;Hematopoiesis;Macrophage-1 Antigen;Muscle, Skeletal;Mice;Muscle Fibers;Luminescent Proteins;Regeneration;Research Support, Non-U.S. Gov't}, Month = {9}, Nlm_Id = {0372516}, Number = {4}, Organization = {Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawa-higashi, Kodaira, Tokyo 187-8502, Japan.}, Pages = {1050-61}, Pii = {S0006-291X(04)01564-5}, Pubmed = {15358135}, Title = {Mac-1(low) early myeloid cells in the bone marrow-derived SP fraction migrate into injured skeletal muscle and participate in muscle regeneration}, Uuid = {44BE0FF7-9644-4C02-9ED9-6CCB7C9AE317}, Volume = {321}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.bbrc.2004.07.069}} @article{Oka:2006, Abstract = {Odorant identity is represented in the olfactory bulb (OB) by the glomerular activity pattern, which reflects a combination of activated odorant receptors (ORs) in the olfactory epithelium. To elucidate this neuronal circuit at the molecular level, we established a functional OR identification strategy based on glomerular activity by combining in vivo Ca(2+) imaging, retrograde dye labeling, and single-cell RT-PCR. Spatial and functional mapping of OR-defined glomeruli revealed that the glomerular positional relationship varied considerably between individual animals, resulting in different OR maps in the OB. Notably, OR-defined glomeruli exhibited different ligand spectra and far higher sensitivity compared to the in vitro pharmacological properties of corresponding ORs. Moreover, we found that the olfactory mucus was an important factor in the regulation of in vivo odorant responsiveness. Our results provide a methodology to examine in vivo glomerular responses at the receptor level and further help address the long-standing issues of olfactory sensitivity and specificity under physiological conditions.}, Author = {Oka, Yuki and Katada, Sayako and Omura, Masayo and Suwa, Makiko and Yoshihara, Yoshihiro and Touhara, Kazushige}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008;13 Olfactory bulb anatomy}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Integrated Biosciences, The University of Tokyo, Chiba 277-8562, Japan.}, Pages = {857-69}, Pii = {S0896-6273(06)00819-1}, Pubmed = {17145506}, Title = {Odorant receptor map in the mouse olfactory bulb: in vivo sensitivity and specificity of receptor-defined glomeruli}, Uuid = {CF40FB77-7426-4744-8399-D72C8F3C7178}, Volume = {52}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.10.019}} @article{Okada:1999, Abstract = {To visualize the movements of cells and their processes in developing vertebrates, we constructed replication-incompetent retroviral vectors encoding green fluorescent protein (GFP) that can be detected as a single integrated copy per cell. To optimize GFP expression, the CMV enhancer and avian beta-actin promoter were incorporated within a retrovirus construct to drive transcription of redshifted (F64L, S65T) and codon-modified GFP (EGFP), EGFP tagged with GAP-43 sequences targeting the GFP to the cell membrane, or EGFP with additional mutations that increase its ability to fold properly at 37 degrees C (S147P or V163A, S175G). We have used these viruses to efficiently mark and follow the developmental progression of a large population of cells in rat neocortex and whole avian embryos. In the chick embryo, the migration and development of GFP-marked neural crest cells were monitored using time-lapse videomicroscopy. In the neocortex, GFP clearly delineates the morphology of a variety of neuronal and glial phenotypes. Cells expressing GFP display normal dendritic morphologies, and infected cells persist into adulthood. Cortical neurons appear to form normal local axonal and long-distance projections, suggesting that the presence of cytoplasmic or GAP-43-tagged GFP does not significantly interfere with normal development. 0014-4886 Journal Article}, Author = {Okada, A. and Lansford, R. and Weimann, J. M. and Fraser, S. E. and McConnell, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Moloney murine leukemia virus;Terminal Repeat Sequences;Cerebral Cortex/cytology/*embryology;Genetic Vectors;Green Fluorescent Proteins;Cytomegalovirus;Vesicular stomatitis-Indiana virus;Luminescent Proteins;Cerebral Cortex;Animals;Neurons/cytology;Dendrites/ultrastructure;Cytomegalovirus/genetics;Axons/ultrastructure;Genes, Reporter;Research Support, U.S. Gov't, P.H.S.;Neural Crest;15 Retrovirus mechanism;Genetic Vectors/*genetics;Actins/genetics;Promoter Regions (Genetics);GAP-43 Protein;Membrane Proteins/analysis/genetics;Dendrites;*Genes, Reporter;Axons;Vesicular stomatitis-Indiana virus/*physiology;Support, U.S. Gov't, P.H.S.;Luminescent Proteins/*analysis/biosynthesis/genetics;Moloney murine leukemia virus/*genetics;Cell Lineage;Rats;Membrane Proteins;Actins;J;Enhancer Elements (Genetics);Microscopy, Video;Recombinant Fusion Proteins;Support, Non-U.S. Gov't;Neural Crest/*cytology;Neurons;GAP-43 Protein/genetics;Research Support, Non-U.S. Gov't;Recombinant Fusion Proteins/analysis/biosynthesis}, Medline = {99263448}, Month = {4}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Biological Sciences, Stanford University, Stanford, California, 94305, USA. amio\@leland.stanford.edu}, Pages = {394-406}, Pii = {S0014-4886(99)97033-4}, Pubmed = {10328944}, Title = {Imaging cells in the developing nervous system with retrovirus expressing modified green fluorescent protein}, Uuid = {54C9EF70-D322-11DA-941C-000D9346EC2A}, Volume = {156}, Year = {1999}, url = {papers/Okada_ExpNeurol1999}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.1999.7033}} @article{Okano:1993, Abstract = {Expression of the cell cycle regulatory proteins RB and p34cdc2 was examined in the adult rat brain, with special emphasis on proliferation and neuronal differentiation in the hippocampal formation and olfactory bulb. RB-like immunoreactivity (RB-IR) was detected throughout the brain, with particularly intense staining observed in hippocampal pyramidal cells, pyriform cortex, and cerebellar Purkinje cells. Intense RB-IR and cdc2-IR were also detected in proliferating neuronal precursor cells in the subgranular region of the dentate gyrus and in the subependymal region extending from the anterior lateral ventricle into the olfactory bulb. Many of these cells developed into neurons as assessed by the expression of neuron-specific enolase (NSE) and, in the hippocampal formation, the expression of Fos-IR following pentylenetetrazol-induced seizure activity. A good correlation was observed between the number of proliferating cells expressing intense nuclear RB-IR staining and the number of thymidine-labeled cells that had differentiated into functional hippocampal neurons. A substantial decrease in RB-IR during differentiation was also observed and occurred prior to the expression of NSE. The possibility that the loss of RB may be necessary for neuronal differentiation to proceed is discussed. eng Journal Article}, Author = {Okano, H. J. and Pfaff, D. W. and Gibbs, R. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Protein p34cdc2/*biosynthesis;Neurons/cytology/*metabolism;Rats;Brain/cytology/*metabolism;Cell Cycle;DNA/*biosynthesis;Animal;Rats, Sprague-Dawley;Kinetics;C abstr;Hippocampus/cytology/*metabolism;Time Factors;Olfactory Bulb/cytology/*metabolism;Male;Thymidine/*metabolism;Retinoblastoma Protein/*biosynthesis;Pyramidal Tracts/cytology/metabolism;Organ Specificity;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Tritium;Autoradiography}, Number = {7}, Organization = {Laboratory of Neurobiology and Behavior, Rockefeller University, New York, New York 10021.}, Pages = {2930-8.}, Title = {RB and Cdc2 expression in brain: correlations with 3H-thymidine incorporation and neurogenesis}, Uuid = {3868963C-28D4-40EC-A6CA-23BA3AF4051F}, Volume = {13}, Year = {1993}} @article{Oldham:2006, Abstract = {Comparisons of gene expression between human and non-human primate brains have identified hundreds of differentially expressed genes, yet translating these lists into key functional distinctions between species has proved difficult. Here we provide a more integrated view of human brain evolution by examining the large-scale organization of gene coexpression networks in human and chimpanzee brains. We identify modules of coexpressed genes that correspond to discrete brain regions and quantify their conservation between the species. Module conservation in cerebral cortex is significantly weaker than module conservation in subcortical brain regions, revealing a striking gradient that parallels known evolutionary hierarchies. We introduce a method for identifying species-specific network connections and demonstrate how differential network connectivity can be used to identify key drivers of evolutionary change. By integrating our results with comparative genomic sequence data and estimates of protein sequence divergence rates, we confirm a number of network predictions and validate these findings. Our results provide insights into the molecular bases of primate brain organization and demonstrate the general utility of weighted gene coexpression network analysis.}, Author = {Oldham, Michael C. and Horvath, Steve and Geschwind, Daniel H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008;19 Neocortical evolution}, Month = {11}, Nlm_Id = {7505876}, Number = {47}, Organization = {Interdepartmental Program for Neuroscience, Program in Neurogenetics, and Semel Institute, David Geffen School of Medicine, Los Angeles, CA 90095-6814, USA.}, Pages = {17973-8}, Pii = {0605938103}, Pubmed = {17101986}, Title = {Conservation and evolution of gene coexpression networks in human and chimpanzee brains}, Uuid = {A421E75A-D73A-43C9-BBB2-1F5B605834E3}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0605938103}} @article{Oleary:2006, Abstract = {The graded expression of transcription factors by progenitors in the ventricular zone (VZ) confers positional or area identity that is inherited by subplate (SP) neurons and governs their expression of guidance molecules for thalamocortical axons and other properties required for cortical area specification. This mechanism would be most efficient if VZ progenitors and their SP neuronal progeny maintain neighbor relationships during the generation of the preplate (PP), the precursor of the SP. Therefore, a major goal of this study is to determine whether progenitors in the cortical VZ and their progeny maintain neighbor relationships during the genesis of the neocortical PP. We used time-lapse video microscopy to follow the movements of VZ progenitors and the radial movement of their progeny and distribution in the PP in whole-mount or slice cortical explants from embryonic rats at stages when PP neurons are generated. We show that labeled VZ cells proliferate and have a strong tendency to retain neighbor relationships within the VZ and that their neuronal progeny move superficially along a radial column to form the overlying PP; during this process, their neuronal progeny also retain neighbor relationships and thereby form the PP in spatial register with the VZ progenitors that generate them. This behavior differs from that reported at later stages of cortical development, when cortical plate (CP) neurons are generated, and considerable dispersion is evident among both cells within the VZ and neuronal progeny as they migrate from the VZ to the CP. However, our findings show that at the early stage of cortical development, when PP/SP neurons are generated, the VZ is, at a cellular level, a "protomap" of the PP/SP.}, Author = {O'leary, Dennis D. M. and Borngasser, Douglass}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {9110718}, Number = {Suppl 1}, Organization = {Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, CA 92037, USA.}, Pages = {i46-i56}, Pii = {16/suppl_1/i46}, Pubmed = {16766707}, Title = {Cortical Ventricular Zone Progenitors and Their Progeny Maintain Spatial Relationships and Radial Patterning during Preplate Development Indicating an Early Protomap}, Uuid = {EF8A93E3-6028-4AD7-925B-B87BA55468AD}, Volume = {16}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhk019}} @article{Olsen:2007, Abstract = {Each odorant receptor gene defines a unique type of olfactory receptor neuron (ORN) and a corresponding type of second-order neuron. Because each odor can activate multiple ORN types, information must ultimately be integrated across these processing channels to form a unified percept. Here, we show that, in Drosophila, integration begins at the level of second-order projection neurons (PNs). We genetically silence all the ORNs that normally express a particular odorant receptor and find that PNs postsynaptic to the silent glomerulus receive substantial lateral excitatory input from other glomeruli. Genetically confining odor-evoked ORN input to just one glomerulus reveals that most PNs postsynaptic to other glomeruli receive indirect excitatory input from the single ORN type that is active. Lateral connections between identified glomeruli vary in strength, and this pattern of connections is stereotyped across flies. Thus, a dense network of lateral connections distributes odor-evoked excitation between channels in the first brain region of the olfactory processing stream.}, Author = {Olsen, Shawn R. and Bhandawat, Vikas and Wilson, Rachel I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;13 Olfactory bulb anatomy;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {89-103}, Pii = {S0896-6273(07)00206-1}, Pubmed = {17408580}, Title = {Excitatory interactions between olfactory processing channels in the Drosophila antennal lobe}, Uuid = {FFA98611-4CCB-4485-BD14-EF47C7629FB4}, Volume = {54}, Year = {2007}, url = {papers/Olsen_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.03.010}} @article{Olson:2006, Abstract = {Reelin and Disabled 1 (Dab1) are essential for positioning migrating neurons in the developing neocortex. Cell-autonomous RNA interference-mediated suppression of Dab1 in migrating neurons destined for layer 2/3 shifted the median position of these cells to deeper positions within the cortex. At the time of migration arrest [embryonic day 20 (E20) to E21], Dab1-suppressed cells were underrepresented in the upper approximately 40 microm of the cortex compared with controls, suggesting that Dab1 is essential for somal translocation through the cell-dense cortical plate. Closer examination of the morphology of Dab1-suppressed neurons at E20 revealed simplified leading processes that are less likely to contact the marginal zone (MZ), in which high levels of Reelin are expressed. Examination of Dab1-suppressed cells 3 d later (postnatal day 2) revealed simplified dendrites that are also less likely to contact the MZ. These data reveal a cell-autonomous role of Dab1 in dendritogenesis in the neocortex and suggest that remodeling of the leading process of a migrating neuron into a nascent dendrite by Reelin/Dab1 signaling plays an important role in cell positioning.}, Author = {Olson, Eric C. and Kim, Seonhee and Walsh, Christopher A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8102140}, Number = {6}, Organization = {Howard Hughes Medical Institute, Beth Israel Deaconess Medical Center, Department of Neurology, Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {1767-75}, Pii = {26/6/1767}, Pubmed = {16467525}, Title = {Impaired neuronal positioning and dendritogenesis in the neocortex after cell-autonomous Dab1 suppression}, Uuid = {61680478-4675-4954-8031-242D49781043}, Volume = {26}, Year = {2006}, url = {papers/Olson_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3000-05.2006}} @article{Olveczky:2005, Abstract = {Songbirds learn their songs by trial-and-error experimentation, producing highly variable vocal output as juveniles. By comparing their own sounds to the song of a tutor, young songbirds gradually converge to a stable song that can be a remarkably good copy of the tutor song. Here we show that vocal variability in the learning songbird is induced by a basal-ganglia-related circuit, the output of which projects to the motor pathway via the lateral magnocellular nucleus of the nidopallium (LMAN). We found that pharmacological inactivation of LMAN dramatically reduced acoustic and sequence variability in the songs of juvenile zebra finches, doing so in a rapid and reversible manner. In addition, recordings from LMAN neurons projecting to the motor pathway revealed highly variable spiking activity across song renditions, showing that LMAN may act as a source of variability. Lastly, pharmacological blockade of synaptic inputs from LMAN to its target premotor area also reduced song variability. Our results establish that, in the juvenile songbird, the exploratory motor behavior required to learn a complex motor sequence is dependent on a dedicated neural circuit homologous to cortico-basal ganglia circuits in mammals.}, Author = {Olveczky, Bence P. and Andalman, Aaron S. and Fee, Michale S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {21 Neurophysiology;Functional Laterality;Stereotaxic Techniques;Tetrodotoxin;Finches;Acoustic Stimulation;Animals;Muscle, Skeletal;24 Pubmed search results 2008;Basal Ganglia;Vocalization, Animal}, Month = {5}, Nlm_Id = {101183755}, Number = {5}, Organization = {McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.}, Pages = {e153}, Pii = {05-PLBI-RA-0094R1}, Pubmed = {15826219}, Title = {Vocal experimentation in the juvenile songbird requires a basal ganglia circuit}, Uuid = {F002337E-5A3B-4248-9D23-F5335957180E}, Volume = {3}, Year = {2005}, url = {papers/Olveczky_PLoSBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0030153}} @article{Omi:2004, Abstract = {The effect of RNA interference (RNAi) induced by synthetic small interfering RNAs (siRNAs) on proliferating mammalian cells appears to last for approximately 3-7 days after its induction. Here we show that the RNAi activity induced by a synthetic 21-nucleotide siRNA duplex in postmitotic neurons, mouse primary hippocampal neurons and neurons that differentiated from mouse embryonal carcinoma P19 cells persists for at least 3 weeks, suggesting long-lasting RNAi activity in mammalian neurons. In addition, we also show that an apoptotic (or antiviral) pathway triggered by long dsRNAs is generated during neuronal differentiation of P19 cells, by which the sequence-specific RNAi activity involving long dsRNA appears to be masked.}, Author = {Omi, Kazuya and Tokunaga, Katsushi and Hohjoh, Hirohiko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:55 -0400}, Issn = {0014-5793}, Journal = {FEBS Lett}, Keywords = {Teratocarcinoma;Cell Differentiation;Animals;Cells, Cultured;Apoptosis;23 Technique;Hippocampus;Cell Line, Tumor;RNA, Small Interfering;Gene Expression Profiling;Time Factors;Mice, Inbred ICR;RNA, Double-Stranded;Support, Non-U.S. Gov't;Cytarabine;Neurons;23 RNAi;Mice;Cell Division;Tretinoin}, Month = {1}, Nlm_Id = {0155157}, Number = {1-3}, Organization = {Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.}, Pages = {89-95}, Pii = {S0014579304000171}, Pubmed = {14759522}, Title = {Long-lasting RNAi activity in mammalian neurons}, Uuid = {6BE750E8-551C-4B19-8F4D-3DF5F98C0662}, Volume = {558}, Year = {2004}, url = {papers/Omi_FEBSLett2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0014-5793(04)00017-1}} @article{Omori:2004, Abstract = {The mechanism that regulates the plasticity of bone marrow cells (BMCs) into hepatocytes is poorly understood. We developed a green fluorescent protein/carbon tetrachloride model to find that BMC transplantation recovered liver damage. Serum albumin level and liver fibrosis were recovered by BMC transplantation. To understand the mechanism, we used DNA-chip technology to profile the change of transient gene expression before and after BMC transplantation. On the basis of gene expression with self-organizing map using specific equation, genes were classified into 153 clusters. The information is useful to understand the dramatic gene activation during the process of the plasticity of BMC.}, Author = {Omori, Kaoru and Terai, Shuji and Ishikawa, Tsuyoshi and Aoyama, Kouji and Sakaida, Isao and Nishina, Hiroshi and Shinoda, Koh and Uchimura, Shunji and Hamamoto, Yoshihiko and Okita, Kiwamu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0014-5793}, Journal = {FEBS Lett}, Keywords = {Research Support, Non-U.S. Gov't;Animals;Gene Expression Regulation;Bone Marrow Transplantation;Oligonucleotide Array Sequence Analysis;Female;Fibrosis;Liver;Mice, Inbred C57BL;11 Glia;Gene Expression Profiling;Green Fluorescent Proteins;Bone Marrow Cells;Multigene Family;Mice;Molecular Sequence Data;Hepatocytes;Carbon Tetrachloride}, Month = {12}, Nlm_Id = {0155157}, Number = {1-2}, Organization = {Department of Molecular Science and Applied Medicine (Gastroenterology and Hepatology), Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755 8505, Japan.}, Pages = {10-20}, Pii = {S0014579304013067}, Pubmed = {15581608}, Title = {Molecular signature associated with plasticity of bone marrow cell under persistent liver damage by self-organizing-map-based gene expression}, Uuid = {9949C92A-E5B5-4042-BC19-B5572A27AD2B}, Volume = {578}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.febslet.2004.09.090}} @article{Onat:2002, Abstract = {The dorsomedial hypothalamic nucleus (DMH) has been implicated as an area controlling autonomic activity. The aim of this study was to demonstrate connections of the anterior and posterior DMH to the forebrain structures, using a horseradish peroxidase (HRP) retrograde axonal transport technique in rats. The results of HRP labelling show that the anterior and posterior DMH indicate a number of differences in their connections. The posterior DMH has intense connections with the cortex (cingulate, frontal, parietal and insular), amygdala (lateral and basolateral) and hippocampus (CA1 and CA2), whereas the anterior DMH has faint connections with the cortex (cingulate, frontal and parietal) and prominent connections with the septal and bed nucleus of stria terminalis. These differences in connections of the DMH may provide sites for the specific autonomic function integrated by the DMH.}, Author = {Onat, Filiz Yilmaz and Aker, Rezzan and Sehirli, Umit and San, Tang{\"u}l and Cavdar, Safiye}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {1422-6405}, Journal = {Cells Tissues Organs}, Keywords = {Research Support, Non-U.S. Gov't;Rats, Sprague-Dawley;Rats;Female;Neural Pathways;Dorsomedial Hypothalamic Nucleus;Brain Mapping;Prosencephalon;Horseradish Peroxidase;Animals;24 Pubmed search results 2008;Neurons}, Medline = {22250784}, Nlm_Id = {100883360}, Number = {1}, Organization = {Department of Pharmacology, Marmara University, School of Medicine, Istanbul, Turkey. fonat\@escortnet.com}, Pages = {48-52}, Pii = {cto72048}, Pubmed = {12364828}, Title = {Connections of the dorsomedial hypothalamic nucleus from the forebrain structures in the rat}, Uuid = {7169CAAA-C619-411D-9305-FADF4B7168C3}, Volume = {172}, Year = {2002}} @article{Ong:1995, Abstract = {Specimens of histologically normal human cerebral cortex and subcortical white matter were obtained during neurosurgical operations and studied by electron microscopy and immunocytochemistry using an antibody against HLA-DR. Greater numbers of labelled cells were present in the white matter than in the overlying cortex. The labelled cells consisted of ramified microglia and perivascular cells. Microglia were often found just outside the walls of small blood vessels, but perivascular cells were actually enclosed by two leaflets of basement membrane in the walls of capillaries, arterioles and venules up to 100 microns in luminal diameter. Labelled microglial processes were often seen enclosing neuronal processes in the cortex and myelinated and unmyelinated axons in the white matter. The enclosed processes appeared healthy, and without features of degenerating neurons. These observations are consistent with a previous suggestion that microglia continually modify the processes of central nervous system neurons by a process of phagocytosis. An intact blood-brain barrier is likely to be of great importance in preventing antigen presentation of the processed neuronal, and perhaps even oligodendrocytic, antigenic peptide fragments to circulating lymphocytes.}, Author = {Ong, W. Y. and Leong, S. K. and Garey, L. J. and Tan, K. K. and Zhang, H. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0021-8359}, Journal = {J Hirnforsch}, Keywords = {Adult;Adolescent;Human;Microscopy, Electron;Tissue Fixation;HLA-DR Antigens;Immunohistochemistry;Female;11 Glia;Not relevant;Male;Brain;Cerebral Cortex;Support, Non-U.S. Gov't}, Medline = {96128828}, Nlm_Id = {0421521}, Number = {4}, Organization = {Department of Anatomy, National University of Singapore, Singapore.}, Pages = {553-63}, Pubmed = {8568227}, Title = {A light and electron microscopic study of HLA-DR positive cells in the human cerebral cortex and subcortical white matter}, Uuid = {895D6CDA-0A68-4C5C-8A98-69E8A2FAB3DF}, Volume = {36}, Year = {1995}} @article{Onifer:1993, Abstract = {A clonal, neuronally-differentiating cell line, RN33B, was previously developed by retroviral infection of neural tissue derived from embryonic Sprague-Dawley raphe nuclei with a retrovirus encoding the temperature-sensitive allele of SV40 large T-antigen. In the present study, RN33B cells were transplanted into two target areas of the raphe nuclei, the spinal cord and hippocampal formation, of adult allogeneic hosts. Prior to transplantation, RN33B cells were infected in vitro with a retroviral vector carrying the Escherichia coli lacZ reporter gene and were visualized in vivo using a beta-galactosidase immunohistochemical technique. RN33B cells were seen throughout the spinal cord and hippocampal formation of the adult hosts at 15 days post-transplantation. T-antigen-immunoreactive nuclei were detected where RN33B cells were observed, but in much greater numbers than beta-galactosidase-immunoreactive cells. Bipolar RN33B cells were found in the spinal cord grey matter. RN33B cells with multipolar morphologies were visualized in the hippocampal and subicular pyramidal cell layers, and also in the dentate gyrus granule cell and polymorph layers, while bipolar RN33B cells were seen in the remainder of the hippocampal formation. The results suggest that immortalized neural cell lines of CNS origin can differentiate in the adult CNS with their ultimate morphology being determined by local tissue signals. We speculate that endogenous neutrophins may significantly influence RN33B cell differentiation in vivo. eng Journal Article}, Author = {Onifer, S. M. and Whittemore, S. R. and Holets, V. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Journal = {Exp Neurol}, Keywords = {Cell Differentiation;Rats, Sprague-Dawley;Rats, Inbred Lew;17 Transplant Regeneration;Lac Operon;Rats;L abstr;Cell Line;Escherichia coli/genetics;Raphe Nuclei/*cytology;Animal;Central Nervous System/*physiology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Neurons/*cytology/*transplantation}, Number = {1}, Organization = {Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami School of Medicine, Florida 33136.}, Pages = {130-42.}, Title = {Variable morphological differentiation of a raphe-derived neuronal cell line following transplantation into the adult rat CNS}, Uuid = {1D42C629-673A-4304-8374-259FDFB128B7}, Volume = {122}, Year = {1993}} @article{Ono:1999, Abstract = {Bone marrow transplantation with GFP-expressing cells from GFP-transgenic mice resulted in migration of GFP-positive cells into peripheral tissues and brain parenchyma. Most of these cells were observed as colony-like clusters. GFP-positive clusters in the brain were stained by antibody for ER-MP12, but those in the peripheral tissues were not. Since ER-MP12 antigen has been reported as a marker for murine early-stage myeloid precursor, this might suggest that some parts of phagocytic cells in the brain parenchyma such as microglia are derived from undifferentiated pluripotent hematopoietic cells.}, Author = {Ono, K. and Takii, T. and Onozaki, K. and Ikawa, M. and Okabe, M. and Sawada, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0006-291X}, Journal = {Biochem Biophys Res Commun}, Keywords = {Lung;Animals;Bone Marrow Transplantation;Brain;Cell Movement;Mice, Transgenic;Liver;11 Glia;Green Fluorescent Proteins;Male;Reverse Transcriptase Polymerase Chain Reaction;Antigens, CD31;Transplantation Chimera;Mice, Inbred Strains;Mesencephalon;Flow Cytometry;Mice;Hematopoietic Stem Cells;Genes, Reporter;Biological Markers;Luminescent Proteins;Spleen;Research Support, Non-U.S. Gov't}, Medline = {99400420}, Month = {9}, Nlm_Id = {0372516}, Number = {3}, Organization = {Faculty of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Aichi, 467-8603, Japan.}, Pages = {610-4}, Pii = {S0006291X99912238}, Pubmed = {10471372}, Title = {Migration of exogenous immature hematopoietic cells into adult mouse brain parenchyma under GFP-expressing bone marrow chimera}, Uuid = {B95E346A-EEE9-49F1-900E-B050588553E7}, Volume = {262}, Year = {1999}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/bbrc.1999.1223}} @article{Ono:1990, Abstract = {(E)-5-(2-Bromovinyl)-2'-deoxyuridine 5'-triphosphate (BrVdUTP) and (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil 5'-triphosphate (BrVarafUTP), which are known as specific inhibitors of herpes simplex viral (type 1 and 2) DNA polymerase, were found to be strong inhibitors of DNA polymerase gamma from human KB and murine myeloma cells. In fact BrVdUTP and BrVarafUTP were found to be stronger inhibitors of DNA polymerase gamma than of other DNA polymerases having viral (herpes simplex virus or retrovirus) origin or cellular (eukaryotic alpha and beta, or prokaryotic) origin. The mode of inhibition of DNA polymerase gamma by BrVdUTP and BrVarafUTP was competitive with respect to dTTP, the normal substrate. Whereas BrVdUTP was an efficient substrate for DNA polymerase gamma and other DNA polymerases that were examined, BrVarafUTP failed to serve as a substrate for DNA synthesis. Ki values for BrVdUTP (40 nM) and BrVarafUTP (7 nM) with DNA polymerase gamma, as determined with (rA)n.(dT) as the template.primer, were much smaller than the Km values for dTTP (0.16 microM and 0.71 microM for murine and human DNA polymerase gamma, respectively). Thus, the affinity of BrVdUTP or BrVarafUTP for DNA polymerase gamma was much stronger than that of dTTP.}, Author = {Ono, K. and Nakane, H. and De Clercq, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0014-2956}, Journal = {Eur J Biochem}, Keywords = {DNA Polymerase I;24 Pubmed search results 2008;Arabinonucleotides;DNA Polymerase II;Kinetics;Simplexvirus;DNA Polymerase III;Cell Line;Antiviral Agents;DNA-Directed DNA Polymerase;DNA Replication;15 Retrovirus mechanism;Animals;Bromodeoxyuridine;Humans;Escherichia coli;KB Cells}, Medline = {90322989}, Month = {7}, Nlm_Id = {0107600}, Number = {3}, Organization = {Laboratory of Viral Oncology, Aichi Cancer Center Research Institute, Nagoya, Japan.}, Pages = {463-7}, Pubmed = {2164928}, Title = {Potent inhibitory effects of the 5'-triphosphates of (E)-5-(2-bromovinyl)-2'-deoxyuridine and (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil on DNA polymerase gamma}, Uuid = {581808D6-ADCC-421D-B88A-E79D5F305E9A}, Volume = {190}, Year = {1990}} @article{Oray:2006, Abstract = {It is increasingly clear that dendritic spines play an important role in compartmentalizing post-synaptic signals and that their dynamic morphological properties have functional consequences. Here, we examine this issue using two-photon microscopy to characterize spine motility on layer V pyramidal neurons in acute slices of the developing mouse cortex. In this system, all spine classes except filopodia become less dynamic as development proceeds. General manipulations of activity (TTX or KCl treatment) do not alter spine dynamics, although increased glutamatergic transmission (AMPA or NMDA treatment) stabilizes developing cortical spines. These effects on spine dynamics do not appear to be related to AMPA or NMDA receptor expression as assessed with immunolabeling, as there is no correlation between spine motility and AMPA (GluR1/2) or NMDA (NR1/NR2B) receptor subunit expression on a spine by spine basis. These results indicate that activity through glutamatergic synapses is important for regulating spine motility in the developing mouse cortex, and that the relative complement of receptors, while different across morphological classifications, cannot account for differences in dynamic structural changes in dendritic spines.}, Author = {Oray, Serkan and Majewska, Ania and Sur, Mriganka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {research support, non-u.s. gov't ;Peptide Fragments;24 Pubmed search results 2008;Immunohistochemistry;Male;Nerve Net;Cerebral Cortex;Animals;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Cell Movement;Synapses;research support, n.i.h., extramural ;21 Circuit structure-function;Dendrites;Excitatory Amino Acid Agonists;Receptors, N-Methyl-D-Aspartate;Potassium Chloride;N-Methylaspartate;Pyramidal Cells;21 Activity-development;Aging;Anesthetics, Local;Tetrodotoxin;Actins;Receptors, AMPA;21 Neurophysiology;Microscopy, Confocal;Mice;Image Processing, Computer-Assisted;Mice, Transgenic}, Month = {5}, Nlm_Id = {9110718}, Number = {5}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, Pages = {730-41}, Pii = {bhj019}, Pubmed = {16120796}, Title = {Effects of synaptic activity on dendritic spine motility of developing cortical layer v pyramidal neurons}, Uuid = {0E7EB116-1C39-41EC-8E08-0C0952AA7259}, Volume = {16}, Year = {2006}, url = {papers/Oray_CerebCortex2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhj019}} @article{Oray:2004, Abstract = {The mammalian primary visual cortex (V1) is especially susceptible to changes in visual input over a well-defined critical period, during which closing one eye leads to a loss of responsiveness of neurons to the deprived eye and a shift in response toward the open eye. This functional plasticity can occur rapidly, following even a single day of eye closure, although the structural bases of these changes are unknown. Here, we show that rapid structural changes at the level of dendritic spines occur following brief monocular deprivation. These changes are evident in the supra- and infragranular layers of the binocular zone and can be mimicked by degradation of the extracellular matrix with the tPA/plasmin proteolytic cascade. Further, monocular deprivation occludes a subsequent effect of matrix degradation, suggesting that this mechanism is active in vivo to permit structural remodeling during ocular dominance plasticity.}, Author = {Oray, Serkan and Majewska, Ania and Sur, Mriganka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Visual Cortex;Sensory Deprivation;research support, non-u.s. gov't;21 Neurophysiology;Mice, Inbred C57BL;Dendritic Spines;in vitro;Extracellular Matrix;comparative study;research support, u.s. gov't, p.h.s.;Animals;Mice;24 Pubmed search results 2008;Vision, Monocular}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.}, Pages = {1021-30}, Pii = {S0896627304007901}, Pubmed = {15603744}, Title = {Dendritic spine dynamics are regulated by monocular deprivation and extracellular matrix degradation}, Uuid = {49DAAC42-F0D9-44C7-92CE-E08FA97B1552}, Volume = {44}, Year = {2004}, url = {papers/Oray_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.12.001}} @article{Orkin:2002, Abstract = {Hematopoietic stem cells (HSCs) provide for blood formation throughout the life of the individual. Studies of HSCs form a conceptual framework for the analysis of stem cells of other organ systems. We review here the origin of HSCs during embryological development, the relationship between hematopoiesis and vascular development and the potential plasticity of HSCs and other tissue stem cells. Recent experiments in the mouse have been widely interpreted as evidence for unprecedented transdifferentiation of tissue stem cells. The use of enriched, but impure, cell populations allows for alternative interpretation. In considering these findings, we draw a distinction here between the plasticity of adult stem cells and the heterogeneity of stem cell types that pre-exist within tissues.}, Author = {Orkin, Stuart H. and Zon, Leonard I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2908}, Journal = {Nat Immunol}, Keywords = {Endothelium, Vascular;Cell Differentiation;Hematopoietic Stem Cells;Hematopoiesis;Research Support, U.S. Gov't, P.H.S.;review, tutorial;Mesoderm;Animals;Humans;review;Yolk Sac}, Medline = {21918612}, Month = {4}, Nlm_Id = {100941354}, Number = {4}, Organization = {Division of Hematology and Oncology, Dana-Farber Cancer Institute and Children's Hospital, Department of Pediatrics, Harvard Medical School and the Howard Hughes Medical Institute, Boston, MA 02115, USA. stuart\_orkin\@dfci.harvard.edu}, Pages = {323-8}, Pii = {ni0402-323}, Pubmed = {11919568}, Title = {Hematopoiesis and stem cells: plasticity versus developmental heterogeneity}, Uuid = {BAA1C86B-C26D-11DA-969D-000D9346EC2A}, Volume = {3}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ni0402-323}} @article{Orlic:2001, Abstract = {Myocardial infarction leads to loss of tissue and impairment of cardiac performance. The remaining myocytes are unable to reconstitute the necrotic tissue, and the post-infarcted heart deteriorates with time. Injury to a target organ is sensed by distant stem cells, which migrate to the site of damage and undergo alternate stem cell differentiation; these events promote structural and functional repair. This high degree of stem cell plasticity prompted us to test whether dead myocardium could be restored by transplanting bone marrow cells in infarcted mice. We sorted lineage-negative (Lin-) bone marrow cells from transgenic mice expressing enhanced green fluorescent protein by fluorescence-activated cell sorting on the basis of c-kit expression. Shortly after coronary ligation, Lin- c-kitPOS cells were injected in the contracting wall bordering the infarct. Here we report that newly formed myocardium occupied 68\%of the infarcted portion of the ventricle 9 days after transplanting the bone marrow cells. The developing tissue comprised proliferating myocytes and vascular structures. Our studies indicate that locally delivered bone marrow cells can generate de novo myocardium, ameliorating the outcome of coronary artery disease.}, Author = {Orlic, D. and Kajstura, J. and Chimenti, S. and Jakoniuk, I. and Anderson, S. M. and Li, B. and Pickel, J. and McKay, R. and Nadal-Ginard, B. and Bodine, D. M. and Leri, A. and Anversa, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Cell Differentiation;Proto-Oncogene Protein c-kit;Connexin 43;DNA-Binding Proteins;Animals;Transcription Factors;Bone Marrow Transplantation;Ki-67 Antigen;Female;Myocardium;Mice, Transgenic;Mice, Inbred C57BL;Green Fluorescent Proteins;Male;Research Support, U.S. Gov't, P.H.S.;Mice;Luminescent Proteins;Myocardial Infarction;Research Support, Non-U.S. Gov't}, Medline = {21184879}, Month = {4}, Nlm_Id = {0410462}, Number = {6829}, Organization = {Hematopoiesis Section, Genetics and Molecular Biology Branch, NHGRI, NIH, Bethesda, MD 20892, USA.}, Pages = {701-5}, Pii = {35070587}, Pubmed = {11287958}, Title = {Bone marrow cells regenerate infarcted myocardium}, Uuid = {BAA1C524-C26D-11DA-969D-000D9346EC2A}, Volume = {410}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35070587}} @article{Orlov:1988, Author = {Orlov, A. A. and Kurzina, N. P. and Shutov, A. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0097-0549}, Journal = {Neurosci Behav Physiol}, Keywords = {Conditioning (Psychology);Rats;Motor Activity;Animals;Male;24 Pubmed search results 2008;Neurons;Frontal Lobe}, Medline = {88261667}, Nlm_Id = {0330471}, Number = {1}, Organization = {Department of Physiology of Higher Nervous Activity, A. A. Zhdanov Leningrad State University.}, Pages = {31-7}, Pubmed = {3386793}, Title = {Activity of medial wall neurons in frontal cortex of rat brain during delayed response reactions}, Uuid = {EBF449DB-B4EA-4A35-9D60-7A126ADD1C25}, Volume = {18}, Year = {1988}} @article{Ory:1996, Abstract = {We have generated a human 293-derived retroviral packaging cell line (293GPG) capable of producing high titers of recombinant Moloney murine leukemia virus particles that have incorporated the vesicular stomatitis virus G (VSV-G) protein. To achieve expression of the retroviral gag-pol polyprotein, the precise coding sequences for gag-pol were introduced into a vector which utilizes totally nonretroviral signals for gene expression. Because constitutive expression of the VSV-G protein is toxic in 293 cells, we used the tetR/VP 16 transactivator and teto minimal promoter system for inducible, tetracycline-regulatable expression of VSV-G. After stable transfection of the 293GPG packaging cell line with the MFG.SnlsLacZ retroviral vector construct, it was possible to readily isolate stable virus-producing cell lines with titers approaching 10(7) colony-forming units/ml. Transient transfection of 293GPG cells using a modified version of MFG.SnlsLacZ, in which the cytomegalovirus IE promoter was used to drive transcription of the proviral genome, led to titers of approximately 10(6) colony-forming units/ml. The retroviral/VSV-G pseudotypes generated using 293GPG cells were significantly more resistant to human complement than commonly used amphotropic vectors and could be highly concentrated (>1000-fold). This new packaging cell line may prove to be particularly useful for assessing the potential use of retroviral vectors for direct in vivo gene transfer. The design of the cell line also provides at least theoretical advantages over existing cell lines with regard to the possible release of replication-competent virus. 0027-8424 Journal Article}, Author = {Ory, D. S. and Neugeboren, B. A. and Mulligan, R. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {RNA-Directed DNA Polymerase;Moloney murine leukemia virus;Blood;Cell Line;Vesicular stomatitis-Indiana virus;Animals;Kidney;3T3 Cells;Transfection/*methods;Base Sequence;Research Support, U.S. Gov't, P.H.S.;Culture Media;Promoter Regions (Genetics);Transfection;15 Retrovirus mechanism;beta-Galactosidase/biosynthesis;*Membrane Glycoproteins;Support, U.S. Gov't, P.H.S.;Viral Envelope Proteins;Viral Envelope Proteins/*biosynthesis/genetics;Moloney murine leukemia virus/*genetics;Membrane Glycoproteins;beta-Galactosidase;J;Recombinant Fusion Proteins;Mice;Vesicular stomatitis-Indiana virus/*genetics/metabolism;Polymerase Chain Reaction;Recombinant Fusion Proteins/*biosynthesis;Humans;DNA Primers;Human;RNA-Directed DNA Polymerase/biosynthesis}, Medline = {97030206}, Month = {10}, Nlm_Id = {7505876}, Number = {21}, Organization = {Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge 02142, USA.}, Pages = {11400-6}, Pubmed = {8876147}, Title = {A stable human-derived packaging cell line for production of high titer retrovirus/vesicular stomatitis virus G pseudotypes}, Uuid = {2D9429E6-AEE1-11DA-A7AA-000D9346EC2A}, Volume = {93}, Year = {1996}, url = {papers/Ory_ProcNatlAcadSciUSA1996.pdf}} @article{Osada:2005, Abstract = {Nuclei isolated from green fluorescent protein-marked neurons in the cerebral cortex of juvenile mice (14-21 d after birth) were injected into enucleated oocytes that were allowed to develop into blastocysts. Embryonic stem (ES) cell lines were established from the inner cell mass of 76 cloned blastocysts after injecting 2026 neuronal nuclei. Some ES cells were injected individually into enucleated oocytes (nuclear transfer). Other ES cells were transferred into the blastocoeles of tetraploid blastocysts (tetraploid complementation). Two-cell embryos after nuclear transfer were transferred to the oviducts of surrogate mothers. Four (1.5\%) of 272 nuclear-transferred two-cell embryos developed to term, and two (0.7\%) developed into fertile adults. Nineteen (1.9\%) of 992 tetraploid blastocysts receiving ES cells reached term, and 10 (1.0\%) developed into adults. These findings demonstrate that some of the nuclei of differentiated neurons in the cerebral cortex of juvenile mice maintain developmental pluripotency.}, Author = {Osada, Tomoharu and Tamamaki, Nobuaki and Song, Si-Young Y. and Kakazu, Naoki and Yamazaki, Yukiko and Makino, Hatsune and Sasaki, Ayako and Hirayama, Teruyoshi and Hamada, Shun and Nave, Klaus-Armin A. and Yanagimachi, Ryuzo and Yagi, Takeshi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {08 Aberrant cell cycle;22 Stem cells;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8102140}, Number = {37}, Organization = {Core Research for Evolutional Science and Technology Research Agency, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan. osada\@libra.ls.m-kagakia.co.jp}, Pages = {8368-74}, Pii = {25/37/8368}, Pubmed = {16162918}, Title = {Developmental pluripotency of the nuclei of neurons in the cerebral cortex of juvenile mice}, Uuid = {DED7D68C-1038-45A6-AC11-7E23B2B9099F}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1591-05.2005}} @article{Osuga:2000, Abstract = {Cyclin-dependent kinases (CDKs) are commonly known to regulate cell proliferation. However, previous reports suggest that in cultured postmitotic neurons, activation of CDKs is a signal for death rather than cell division. We determined whether CDK activation occurs in mature adult neurons during focal stroke in vivo and whether this signal was required for neuronal death after reperfusion injury. Cdk4/cyclin D1 levels and phosphorylation of its substrate retinoblastoma protein (pRb) increase after stroke. Deregulated levels of E2F1, a transcription factor regulated by pRb, are also observed. Administration of a CDK inhibitor blocks pRb phosphorylation and the increase in E2F1 levels and dramatically reduces neuronal death by 80\%. These results indicate that CDKs are an important therapeutic target for the treatment of reperfusion injury after ischemia. 0027-8424 Journal Article}, Author = {Osuga, H. and Osuga, S. and Wang, F. and Fetni, R. and Hogan, M. J. and Slack, R. S. and Hakim, A. M. and Ikeda, J. E. and Park, D. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Animals;Rats;Enzyme Inhibitors/*pharmacology;Neurons/pathology/physiology;*Cell Cycle Proteins;Reperfusion Injury/*prevention &control;Cyclin-Dependent Kinases/*antagonists &inhibitors/metabolism;Apoptosis;EE pdf;Rats, Sprague-Dawley;Transcription Factors/metabolism;*Carrier Proteins;08 Aberrant cell cycle;Male;Support, Non-U.S. Gov't;Cerebrovascular Circulation/*drug effects/physiology;Brain/blood supply/pathology/physiopathology;Ischemic Attack, Transient/enzymology/*physiopathology;Piperidines/*pharmacology;Flavonoids/*pharmacology;Cyclin D1/metabolism}, Number = {18}, Organization = {Department of Molecular Neuroscience, Institute of Medical Sciences, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan 259-1193.}, Pages = {10254-9}, Pubmed = {10944192}, Title = {Cyclin-dependent kinases as a therapeutic target for stroke}, Uuid = {88EAA8AC-0384-4F50-952D-85599D95B8E5}, Volume = {97}, Year = {2000}, url = {papers/Osuga_ProcNatlAcadSciUSA2000.pdf}} @article{Otaki:1999, Abstract = {Neurestin is a putative transmembrane protein whose expression is developmentally regulated in neurons. Here we examined neurestin expression pattern in mitral/tufted cells in the developing rat olfactory bulb. In the main olfactory bulb, neurestin expression was segregated in the dorso-rostral area and in the ventro-caudal area, but not in between. In the accessory olfactory bulb, neurestin expression was found only in the far caudal area. This area did not completely correspond to a caudal half of the vomeronasal nerve and glomerular layers positive for a G-protein Go alpha. These spatio-temporal expression patterns suggest that neurestin functions as a target recognition molecule that specifies zonal projection patterns of olfactory and vomeronasal sensory neurons.}, Author = {Otaki, J. M. and Firestein, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Neuroreport}, Keywords = {In Situ Hybridization;*Brain Mapping;Membrane Proteins/*biosynthesis;Rats, Sprague-Dawley;Rats;Animal;Support, U.S. Gov't, P.H.S.;I abstr;Nerve Tissue Proteins/*biosynthesis;Fetal Development/physiology;13 Olfactory bulb anatomy;Olfactory Bulb/embryology/growth &development/*metabolism}, Number = {12}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {2677-80.}, Title = {Segregated expression of neurestin in the developing olfactory bulb}, Uuid = {DFC21454-DFDA-48D1-9798-088B86EA236C}, Volume = {10}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10574391}} @article{Otsubo:1997, Abstract = {Most epileptiform abnormalities show a negative polarity on EEG. Focal positive spike waves have rarely been identified in seizure disorders and are generally associated with physiological and neurological impairment. Results of EEG, computed tomography, MRI, and pathologic studies of 15 children with focal neuronal migration disorders who underwent surgery for refractory localization-related epilepsy were compared to examine the association between positive discharges and other findings. Subjects were studied both ictally and interictally by scalp EEG with the International 10-20 system and zygomatic or sphenoidal electrodes, and video EEG telemetry. The 5 children with positive discharges were significantly more likely to develop hemiparesis during the preoperative period (P < or = .025). Correlations were observed between positive discharges and lesions apparent on MRI situated around the rolandic fissure (P < or = .025). Children with positive discharges had a significantly less favorable outcome after surgical treatment (P < or = .025). Positive epilepti-form discharges in children with neuronal migration disorders may signal a more dysfunctional cortex leading to a focal neurological deficit or a more extended lesion than is detected on MRI. This would explain the less favorable outcome of seizures after surgery, since the epileptogenic areas and neuronal migration lesions cannot be completely resected.}, Author = {Otsubo, H. and Steinlin, M. and Hwang, P. A. and Sharma, R. and Jay, V. and Becker, L. E. and Hoffman, H. J. and Blaser, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0887-8994}, Journal = {Pediatr Neurol}, Keywords = {Spasms, Infantile;Research Support, Non-U.S. Gov't;Dominance, Cerebral;Magnetic Resonance Imaging;Epilepsies, Partial;Child, Preschool;Evoked Potentials;Humans;Brain;21 Epilepsy;Female;Cell Movement;Infant;Tomography, X-Ray Computed;Male;Cerebral Cortex;21 Neurophysiology;Neurons;Telemetry;Infant, Newborn;24 Pubmed search results 2008;Electroencephalography;Brain Mapping}, Medline = {97197337}, Month = {1}, Nlm_Id = {8508183}, Number = {1}, Organization = {Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.}, Pages = {23-31}, Pii = {S0887899496002548}, Pubmed = {9044397}, Title = {Positive epileptiform discharges in children with neuronal migration disorders}, Uuid = {6A028EDD-87D2-44BB-BE44-34F05A95FDF3}, Volume = {16}, Year = {1997}} @article{Ourednik:1998, Abstract = {Remodeling of the mechanically injured cerebral cortex of kittens was studied in the presence of a neural xenograft taken from mouse fetuses. Solid neural tissue from the neopallium of a 14-day-old fetus was transferred into a cavity prepared in visual cortical area 18 of 33-day-old kittens. Injections of bromodeoxyuridine (BrdU) were used to monitor postoperative cell proliferation. Two months after transplantation, the presence of graft tissue in the recipient brain was assessed by Thy-1 immunohistochemistry. Antibodies specific for neurons, astrocytes, and oligodendrocytes and hematoxylin staining for endothelial cells were used for the characterization of proliferating (BrdU+) cells. The following were the major observations: 1) Of ten transplanted kittens, four had the cavity completely filled with neural tissue that resembled the intact cerebral cortex in its cytoarchitecture, whereas, in four other kittens, the cavity was partially closed. In two kittens, the cavity remained or became larger, which was also the case with all four sham-operated (lesioned, without graft) animals. 2) A substantial part of the remodeled tissue was of host origin. Only a few donor cells survived and dispersed widely in the host parenchyme. 3) In the remodeled region of transplanted animals, the densities of nerve, glial, and endothelial cells were similar to those in intact animals. 4) Cell proliferation increased after transplantation but only within a limited time, because, 2 months after the operation, the number of mitotic cells in the grafted cerebral cortex did not differ from that in intact controls. Our data suggest that the xenograft evokes repair processes in the kitten visual cortex that lead to structural recovery from a mechanical insult. The regeneration seems to rely on a complex interplay of many different mechanisms, including attenuation of necrosis, cell proliferation, and immigration of host cells into the wounded area.}, Author = {Ourednik, J. and Ourednik, W. and Mitchell, D. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Visual Cortex;24 Pubmed search results 2008;Transplantation, Heterologous;Research Support, Non-U.S. Gov't;Cats;Immunohistochemistry;Neuronal Plasticity;Female;Mice, Inbred C57BL;Neocortex;Animals;Mice;Male;Fetal Tissue Transplantation;Bromodeoxyuridine}, Medline = {98250430}, Month = {5}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Psychology, Life Sciences Center, Dalhousie University, Halifax, Nova Scotia, Canada. jitka.ourednik\@neuro.biol.ethz.ch}, Pages = {91-111}, Pii = {10.1002/(SICI)1096-9861(19980525)395:1<91::AID-CNE7>3.0.CO;2-C}, Pubmed = {9590548}, Title = {Remodeling of lesioned kitten visual cortex after xenotransplantation of fetal mouse neopallium}, Uuid = {DC986010-0770-41E7-B000-5536682AC86F}, Volume = {395}, Year = {1998}} @article{Ourednik:2001, Abstract = {Many central nervous system regions at all stages of life contain neural stem cells (NSCs). We explored how these disparate NSC pools might emerge. A traceable clone of human NSCs was implanted intraventricularly to allow its integration into cerebral germinal zones of Old World monkey fetuses. The NSCs distributed into two subpopulations: One contributed to corticogenesis by migrating along radial glia to temporally appropriate layers of the cortical plate and differentiating into lamina-appropriate neurons or glia; the other remained undifferentiated and contributed to a secondary germinal zone (the subventricular zone) with occasional members interspersed throughout brain parenchyma. An early neurogenetic program allocates the progeny of NSCs either immediately for organogenesis or to undifferentiated pools for later use in the "postdevelopmental"brain. 0036-8075 Journal Article}, Author = {Ourednik, V. and Ourednik, J. and Flax, J. D. and Zawada, W. M. and Hutt, C. and Yang, C. and Park, K. I. and Kim, S. U. and Sidman, R. L. and Freed, C. R. and Snyder, E. Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Science}, Keywords = {10 Development;Cell Differentiation;Human;Animals;Stem Cell Transplantation;Brain Tissue Transplantation;Transplantation, Heterologous;Stem Cells/*cytology;*Cell Movement;Macaca radiata/embryology;Prosencephalon/*cytology/*embryology;Cell Lineage;Support, Non-U.S. Gov't;Clone Cells/cytology/transplantation;Neurons/*cytology/transplantation;Cell Transplantation;Neocortex/*cytology/*embryology;F}, Number = {5536}, Organization = {Department of Pediatrics, Children's Hospital, Harvard Medical School, 248 Enders Building, 300 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {1820-4}, Pubmed = {11474066}, Title = {Segregation of human neural stem cells in the developing primate forebrain}, Uuid = {0196E2E7-7C2B-451B-BF39-F60F9A438750}, Volume = {293}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11474066}} @article{Overstreet:2004, Abstract = {Neurogenesis in the dentate gyrus continues into adulthood, yet little is known about the function of newly born neurons or how they integrate into an existing network of mature neurons. We made transgenic mice that selectively and transiently express enhanced green fluorescent protein (EGFP) in newly born granule cells of the dentate gyrus under the transcriptional control of proopiomelanocortin (POMC) genomic sequences. Analysis of transgenic pedigrees with truncation or deletion mutations indicated that EGFP expression in the dentate gyrus required cryptic POMC promoter regions dispensable for arcuate hypothalamic or pituitary expression. Unlike arcuate neurons, dentate granule cells did not express the endogenous POMC gene. EGFP-positive neurons had immature properties, including short spineless dendrites and small action potentials. Colocalization with bromodeoxyuridine indicated that EGFP-labeled granule cells were approximately 2 weeks postmitotic. EGFP-labeled cells expressed markers for immature granule cells but not the glial marker GFAP. The number of EGFP-labeled neurons declined with age and increased with exercise, paralleling neurogenesis. Our results indicate that POMC-EGFP marks immature granule cells and that adult-generated granule cells integrate quite slowly into the hippocampal circuitry.}, Author = {Overstreet, Linda S. and Hentges, Shane T. and Bumaschny, Viviana F. and de Souza, Flavio S. J. and Smart, James L. and Santangelo, Andrea M. and Low, Malcolm J. and Westbrook, Gary L. and Rubinstein, Marcelo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Genes, Reporter;Exertion;Animals;Aging;Cell Count;Mice, Transgenic;Cell Movement;Mice, Inbred C57BL;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;Action Potentials;Sialic Acids;Pro-Opiomelanocortin;Dentate Gyrus;Neurons;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Luminescent Proteins;Biological Markers;Bromodeoxyuridine;Promoter Regions (Genetics);Neural Cell Adhesion Molecule L1;Transgenes}, Month = {3}, Nlm_Id = {8102140}, Number = {13}, Organization = {Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. overstre\@ohsu.edu}, Pages = {3251-9}, Pii = {24/13/3251}, Pubmed = {15056704}, Title = {A transgenic marker for newly born granule cells in dentate gyrus}, Uuid = {D04106EE-E28D-4D50-92CC-A51B5E595DC4}, Volume = {24}, Year = {2004}, url = {papers/Overstreet_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5173-03.2004}} @article{Wadiche:2005, Abstract = {Neurogenesis in the dentate gyrus begins before birth, but then continues into adulthood. Consequently, many newborn granule cells must integrate into a pre-existing hippocampal network. Little is known about the timing of this process or the characteristics of the first established synapses. We used mice that transiently express EGFP in newborn granule cells to examine their synaptic input. Although newborn granule cells had functional glutamate receptors, evoked and spontaneous synaptic currents were exclusively GABAergic with immature characteristics including slow rise and decay phases and depolarized reversal potentials. Synaptic currents in newborn granule cells were relatively insensitive to the GABAA receptor modulator zolpidem compared to neighboring mature granule cells. Consistent with the kinetics and pharmacology, newborn granule cells isolated by fluorescent cell sorting lacked the alpha1 GABAA receptor subunit. Our results indicate that newborn granule cells initially receive only GABAergic synapses even in the adult.}, Author = {Overstreet Wadiche, and Bromberg, and Bensen, and Westbrook,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {0375404}, Organization = {Oregon Health & Science University, Vollum Institute, Portland, OR, USA.}, Pii = {00633.2005}, Pubmed = {16033936}, Title = {GABAergic Signaling to Newborn Neurons in Dentate Gyrus}, Uuid = {07003BB4-C456-4521-A63C-E38F2CBDB8F3}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00633.2005}} @article{Overstreet-Wadiche:2006, Abstract = {A substantial fraction of adult-generated granule cells in the dentate gyrus survive and integrate into the existing neuronal network. These newborn neurons must navigate the environment of the adult brain, a setting that is presumably less optimized for neuronal maturation compared with that in the developing brain. We used EGFP (enhanced green fluorescent protein) expression in newborn granule cells to compare the maturation of adult-generated granule cells to those generated in neonates. Labeled newborn granule cells had indistinguishable physiological properties in adults and neonates, indicating they were at the same functional stage. However, the maturation of adult-generated granule cells was slower than neonatal-generated granule cells. Depolarizing GABAergic network activity and transcription factor activation were reduced in adults relative to neonates, suggesting a role for neural activity in the maturation of newborn granule cells. Consistent with this idea, maturation was altered in mice lacking the GABA synthetic enzyme GAD65 (glutamic acid decarboxylase 65). Together, these results provide evidence that activity-dependent processes in the local environment influence the maturation of newborn granule cells.}, Author = {Overstreet-Wadiche, Linda S. and Bensen, Aesoon L. and Westbrook, Gary L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Aging;Neurons;24 Pubmed search results 2008;research support, n.i.h., extramural ;Nerve Regeneration;Cell Proliferation;Hippocampus;Mice, Inbred C57BL;Time Factors;Animals, Newborn;Animals;comparative study ;Cells, Cultured;Cerebellar Nuclei;Mice}, Month = {2}, Nlm_Id = {8102140}, Number = {8}, Organization = {Vollum Institute, L474, Oregon Health & Science University, Portland, Oregon 97239, USA. overstre\@ohsu.edu}, Pages = {2326-34}, Pii = {26/8/2326}, Pubmed = {16495460}, Title = {Delayed development of adult-generated granule cells in dentate gyrus}, Uuid = {5CDCFAD3-A40A-4B9D-BEC7-FC82634890BE}, Volume = {26}, Year = {2006}, url = {papers/Overstreet-Wadiche_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4111-05.2006}} @article{Overstreet-Wadiche:2006a, Abstract = {In humans and experimental animals, structural and functional changes in neural circuits can accompany the development of epilepsy. In the dentate gyrus, seizures enhance adult neurogenesis, but it is unclear to what extent newborn granule cells participate in seizure-induced synaptic reorganization. During the first weeks of their existence, mouse newborn granule cells labeled with enhanced green fluorescent protein have only short dendrites that lack excitatory input. We report that pilocarpine-induced seizures accelerated the morphological development of labeled granule cells, causing their dendrites to extend through the molecular layer. In whole-cell recordings 5-16 d after seizure induction, perforant-path stimulation now evoked glutamatergic input to newborn granule cells. These synaptic responses were mediated by monosynaptic as well as recurrent polysynaptic input. Thus, seizures facilitated functional integration of adult-generated granule cells. One month later, subsequent generations of newborn cells also showed alterations in dendrite morphology, suggesting persistent effects of seizures on granule cell maturation. The sensitivity of newborn granule cells to seizures could contribute to hyperexcitability during the latent period.}, Author = {Overstreet-Wadiche, Linda S. and Bromberg, Daniel A. and Bensen, Aesoon L. and Westbrook, Gary L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {15}, Organization = {Vollum Institute, L474, Oregon Health and Science University, Portland, Oregon 97239, USA. overstre\@ohsu.edu}, Pages = {4095-103}, Pii = {26/15/4095}, Pubmed = {16611826}, Title = {Seizures accelerate functional integration of adult-generated granule cells}, Uuid = {A28CE264-D3F0-4579-ABB4-582CC192F03F}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5508-05.2006}} @article{Owens:2000, Abstract = {Cell-cell signaling within the neocortical ventricular zone (VZ) has been shown to influence the proliferation of VZ precursor cells and the subsequent differentiation and fate of postmitotic neurons. Calcium (Ca(2+)), a ubiquitous second messenger implicated in the regulation of many aspects of development, may play a role in these signaling events. Accordingly, we have examined the spatiotemporal patterns of spontaneous intracellular free Ca(2+) ([Ca(2+)](i)) fluctuations of cells within the intact neocortical VZ. Previous observations have demonstrated that similar patterns of spontaneous [Ca(2+)](i) increase occur in both proliferative and postmitotic cortical cells, suggesting that they may be mechanistically similar. Our results suggest that the changes in [Ca(2+)](i) in VZ cells and cortical plate neurons are likely triggered by different mechansims, and imply that similar changes in [Ca(2+)](i) may underlie different signaling events during distinct phases of neocortical development.}, Author = {Owens, D. F. and Flint, A. C. and Dammerman, R. S. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Ryanodine Receptor Calcium Release Channel;Animals;Osmolar Concentration;Rats;Neocortex;Cycloleucine;Rats, Sprague-Dawley;Calcium;Embryonic and Fetal Development;Embryo;Cerebral Ventricles;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Neurons;Mice;Receptors, Metabotropic Glutamate;24 Pubmed search results 2008;Intracellular Membranes;Research Support, Non-U.S. Gov't}, Medline = {20125897}, Nlm_Id = {7809375}, Number = {1-2}, Organization = {Department of Neurology, The Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, N.Y., USA.}, Pages = {25-33}, Pii = {dne22025}, Pubmed = {10657695}, Title = {Calcium dynamics of neocortical ventricular zone cells}, Uuid = {D36C1A31-1C93-45F1-AF0E-6A8CAC909102}, Volume = {22}, Year = {2000}} @article{Owens:1996, Abstract = {Gramicidin perforated-patch-clamp recordings in brain slices were used to obtain an accurate assessment of the developmental change in the GABAA receptor reversal potential (EGABAA) in embryonic and early postnatal rat neocortical cells including neuroepithelial precursor cells, cortical plate neurons, and postnatal neocortical neurons. Our results demonstrate that there is a progressive negative shift in EGABAA with the most positive values found in the youngest cortical precursor cells. At the early stages of neocortical development, EGABAA is determined by the chloride (Cl-) gradient, and the internal chloride concentration ([Cl-]i) decreases with development. EGABAA is positive to the resting potential, indicating that GABA serves to depolarize developing neocortical cells. Consistent with this conclusion, GABAA receptor activation with muscimol was found-to increase the internal calcium concentration ([Ca2+]i) in both embryonic and early postnatal neocortical cells through the activation of voltage-gated calcium channels (VGCCs). Postnatal cells exhibit spontaneous postsynaptic synaptic currents, which are eliminated by bicuculline methiodide (BMI) but not glutamate receptor antagonists and reverse at the Cl- equilibrium potential. Likewise, brief spontaneous increases in [Ca2+]i, sensitive to BMI and TTX, are observed at the same ages, suggesting that endogenous synaptic GABAA receptor activation can depolarize cells and activate VGCCs. These results suggest that GABAA receptor-mediated depolarization may influence early neocortical developmental events, including neurogenesis and synaptogenesis, through the activation of Ca(2+)-dependent signal transduction pathways.}, Author = {Owens, D. F. and Boyce, L. H. and Davis, M. B. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Research Support, U.S. Gov't, P.H.S.;Time Factors;Calcium;Receptors, GABA;Animals, Newborn;Gramicidin;Muscimol;Animals;Patch-Clamp Techniques;Cerebral Cortex;gamma-Aminobutyric Acid;24 Pubmed search results 2008}, Medline = {97000877}, Month = {10}, Nlm_Id = {8102140}, Number = {20}, Organization = {Department of Neurology, College of Physicians and Surgeons of Columbia University, New York, New York 10025, USA.}, Pages = {6414-23}, Pubmed = {8815920}, Title = {Excitatory GABA responses in embryonic and neonatal cortical slices demonstrated by gramicidin perforated-patch recordings and calcium imaging}, Uuid = {072DC703-F92E-4B7C-BA93-91C0AB7F787C}, Volume = {16}, Year = {1996}} @article{Owens:1998, Abstract = {Changes in intracellular free calcium concentration ([Ca2+]i) are known to influence a variety of events in developing neurons. Although spontaneous changes of [Ca2+]i have been examined in immature cortical neurons, the calcium dynamics of cortical precursor cells have received less attention. Using an intact cortical mantle and confocal laser microscopy, we examined the spatiotemporal patterns of spontaneous [Ca2+]i fluctuations in neocortical ventricular zone (VZ) cells in situ. The majority of activity consisted of single cells that displayed independent [Ca2+]i fluctuations. These events occurred in cells throughout the depth of the VZ. Immunohistochemical staining confirmed that these events occurred primarily in precursor cells rather than in postmitotic neurons. When imaging near the ventricular surface, synchronous spontaneous [Ca2+]i increases were frequently observed in pairs of adjacent cells. Cellular morphology, time-lapse imaging, and nuclear staining demonstrated that this activity occurred in mitotically active cells. A third and infrequently encountered pattern of activity consisted of coordinated spontaneous increases in [Ca2+]i in groups of neighboring VZ cells. The morphological characteristics of these cells and immunohistochemical staining suggested that the coordinated events occurred in gap junction-coupled precursor cells. All three patterns of activity were dependent on the release of Ca2+ from intracellular stores. These results demonstrate distinct patterns of spontaneous [Ca2+]i change in cortical precursor cells and raise the possibility that these dynamics may contribute to the regulation of neurogenesis.}, Author = {Owens, D. F. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;21 Neurophysiology;Immunohistochemistry;Cell Aging;Research Support, U.S. Gov't, P.H.S.;Time Factors;Rats;Stem Cells;Calcium;In Vitro;Animals;Cerebral Ventricles;24 Pubmed search results 2008;Neurons}, Medline = {98315211}, Month = {7}, Nlm_Id = {8102140}, Number = {14}, Organization = {Department of Neurology and The Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.}, Pages = {5374-88}, Pubmed = {9651220}, Title = {Patterns of intracellular calcium fluctuation in precursor cells of the neocortical ventricular zone}, Uuid = {7D283158-88C7-4D55-8C00-441E5B7B5CDC}, Volume = {18}, Year = {1998}} @article{Owens:2002, Abstract = {In the mature brain, GABA (gamma-aminobutyric acid) functions primarily as an inhibitory neurotransmitter. But it can also act as a trophic factor during nervous system development to influence events such as proliferation, migration, differentiation, synapse maturation and cell death. GABA mediates these processes by the activation of traditional ionotropic and metabotropic receptors, and probably by both synaptic and non-synaptic mechanisms. However, the functional properties of GABA receptor signalling in the immature brain are significantly different from, and in some ways opposite to, those found in the adult brain. The unique features of the early-appearing GABA signalling systems might help to explain how GABA acts as a developmental signal.}, Author = {Owens, David F. and Kriegstein, Arnold R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Gene Expression Regulation, Developmental;10 Development;Cell Differentiation;Central Nervous System;Presynaptic Terminals;Signal Transduction;Neural Inhibition;Receptors, GABA;gamma-Aminobutyric Acid;Synaptic Transmission;Humans;Animals;Nerve Growth Factors;review}, Medline = {22199620}, Month = {9}, Nlm_Id = {100962781}, Number = {9}, Organization = {Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, Building 36, Room 3C09, 36 Convent Drive, Bethesda, Maryland 20892-4092, USA.}, Pages = {715-27}, Pii = {nrn919}, Pubmed = {12209120}, Title = {Is there more to GABA than synaptic inhibition?}, Uuid = {FBEBE0B4-D067-11DA-8A8C-000D9346EC2A}, Volume = {3}, Year = {2002}, url = {papers/Owens_NatRevNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn919}} @article{Packer:2003, Abstract = {Neural progenitor cells are widespread throughout the adult central nervous system but only give rise to neurons in specific loci. Negative regulators of neurogenesis have therefore been postulated, but none have yet been identified as subserving a significant role in the adult brain. Here we report that nitric oxide (NO) acts as an important negative regulator of cell proliferation in the adult mammalian brain. We used two independent approaches to examine the function of NO in adult neurogenesis. In a pharmacological approach, we suppressed NO production in the rat brain by intraventricular infusion of an NO synthase inhibitor. In a genetic approach, we generated a null mutant neuronal NO synthase knockout mouse line by targeting the exon encoding active center of the enzyme. In both models, the number of new cells generated in neurogenic areas of the adult brain, the olfactory subependyma and the dentate gyrus, was strongly augmented, which indicates that division of neural stem cells in the adult brain is controlled by NO and suggests a strategy for enhancing neurogenesis in the adult central nervous system. 0027-8424 Journal Article}, Author = {Packer, M. A. and Stasiv, Y. and Benraiss, A. and Chmielnicki, E. and Grinberg, A. and Westphal, H. and Goldman, S. A. and Enikolopov, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {NG-Nitroarginine Methyl Ester/pharmacology;Central Nervous System/metabolism;Bromodeoxyuridine/pharmacology;Nitric-Oxide Synthase/metabolism;Rats;Animals;Microscopy, Confocal;Exons;Neurons/*metabolism/*physiology;Open Reading Frames;Models, Genetic;Nitric Oxide/*metabolism;Support, Non-U.S. Gov't;In Situ Nick-End Labeling;Mice, Knockout;Recombination, Genetic;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Molecular Sequence Data;C pdf;Brain/metabolism}, Number = {16}, Organization = {Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.}, Pages = {9566-71}, Title = {Nitric oxide negatively regulates mammalian adult neurogenesis}, Uuid = {6B46DAFA-5804-4644-9FB6-87D6E306D47C}, Volume = {100}, Year = {2003}, url = {papers/Packer_ProcNatlAcadSciUSA2003.pdf}} @article{Pagano:2004, Abstract = {The family of cyclin-dependent kinases (Cdks) lies at the core of the machinery that drives the cell division cycle. Studies in cultured mammalian cells have provided insight into the cellular functions of many Cdks. Recent Cdk and cyclin knockouts in the mouse show that the functions of G1 cell cycle regulatory genes are often essential only in specific cell types, pointing to our limited understanding of tissue-specific expression, redundancy, and compensating mechanisms in the Cdk network.}, Author = {Pagano, Michele and Jackson, Peter K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:55 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Embryo;Cell Differentiation;10 Development;Gene Expression Regulation, Developmental;G1 Phase;Cyclin-Dependent Kinases;Genes, cdc;Signal Transduction;Cyclins;review, tutorial;Mice;Animals;review;Organogenesis}, Month = {9}, Nlm_Id = {0413066}, Number = {5}, Organization = {Department of Pathology and NYU Cancer Institute, New York University School of Medicine, New York, NY 10016, USA. michele.pagano\@med.nyu.edu}, Pages = {535-8}, Pii = {S0092867404007949}, Pubmed = {15339658}, Title = {Wagging the dogma; tissue-specific cell cycle control in the mouse embryo}, Uuid = {FE61C8B1-5636-4C20-91E6-C1825274BF9D}, Volume = {118}, Year = {2004}, url = {papers/Pagano_Cell2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.08.013}} @article{Pak:2004, Abstract = {Pathfinding of retinal ganglion cell (RGC) axons at the midline optic chiasm determines whether RGCs project to ipsilateral or contralateral brain visual centers, critical for binocular vision. Using Isl2tau-lacZ knockin mice, we show that the LIM-homeodomain transcription factor Isl2 marks only contralaterally projecting RGCs. The transcription factor Zic2 and guidance receptor EphB1, required by RGCs to project ipsilaterally, colocalize in RGCs distinct from Isl2 RGCs in the ventral-temporal crescent (VTC), the source of ipsilateral projections. Isl2 knockout mice have an increased ipsilateral projection originating from significantly more RGCs limited to the VTC. Isl2 knockouts also have increased Zic2 and EphB1 expression and significantly more Zic2 RGCs in the VTC. We conclude that Isl2 specifies RGC laterality by repressing an ipsilateral pathfinding program unique to VTC RGCs and involving Zic2 and EphB1. This genetic hierarchy controls binocular vision by regulating the magnitude and source of ipsilateral projections and reveals unique retinal domains.}, Author = {Pak, Winnie and Hindges, Robert and Lim, Yoo-Shick S. and Pfaff, Samuel L. and O'Leary, Dennis D. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Transcription Factors;Retina;research support, u.s. gov't, p.h.s. ;24 Pubmed search results 2008;21 Neurophysiology;Functional Laterality;Receptor, EphB2;Nerve Tissue Proteins;Gene Expression Regulation;Vision, Binocular;Mice, Mutant Strains;Retinal Ganglion Cells;Animals;Mice;Homeodomain Proteins;Visual Pathways;Axons}, Month = {11}, Nlm_Id = {0413066}, Number = {4}, Organization = {Molecular Neurobiology Lab, The Salk Institute, La Jolla, CA 92037, USA.}, Pages = {567-78}, Pii = {S0092867404010037}, Pubmed = {15537545}, Title = {Magnitude of binocular vision controlled by islet-2 repression of a genetic program that specifies laterality of retinal axon pathfinding}, Uuid = {B803129D-4B21-4A2A-8929-85F6F00BE673}, Volume = {119}, Year = {2004}, url = {papers/Pak_Cell2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.10.026}} @article{Pal:1988, Abstract = {We are using fluorescent endogenous phospholipids in virus membranes to study the factors that promote fusion on interaction with receptor membranes. To this end, vesicular stomatitis virus (VSV) grown in baby hamster kidney (BHK-21) cells was biologically labeled with fluorescent lipids, primarily phosphatidylcholine and phosphatidylethanolamine, derived from pyrene fatty acids. The pyrene lipids present in the virions showed a fluorescence spectrum typical of pyrene with an intense monomer and a broad excimer. Interaction of pyrene lipid labeled VSV with serum lipoproteins led to a spontaneous fast transfer of the small amount of pyrene fatty acids present in the envelope (t1/2 less than or equal to 7 min), followed by a considerably slower transfer of pyrene phospholipids from the membrane of the virions (t1/2 greater than or equal to 12 h). Incubation of pyrene phospholipid labeled VSV with phosphatidylserine small unilamellar vesicles resulted in fusion at low pH (pH 5.0) as measured by the change in the excimer/monomer fluorescence intensity ratio. Fusion kinetics was rapid, reaching a plateau after 4 min at pH 5.0 and 37 degrees C. Only negligible fusion was noted at neutral pH or at 4 degrees C. Fully infectious virions labeled biologically with fluorescent lipids provide a useful tool for studying mechanisms of cell-virus interactions and neutralization of viral infectivity by specific monoclonal antibodies reactive with viral membrane glycoprotein.}, Author = {Pal, R. and Barenholz, Y. and Wagner, R. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0006-2960}, Journal = {Biochemistry}, Keywords = {Membrane Lipids;Phospholipids;Research Support, Non-U.S. Gov't;Kinetics;Liposomes;Research Support, U.S. Gov't, P.H.S.;Cell Line;Lipid Bilayers;Fluorescent Dyes;Receptors, Virus;Pyrenes;Vesicular stomatitis-Indiana virus;15 Retrovirus mechanism;24 Pubmed search results 2008}, Medline = {88163585}, Month = {1}, Nlm_Id = {0370623}, Number = {1}, Organization = {Department of Microbiology, University of Virginia School of Medicine, Charlottesville 22908.}, Pages = {30-6}, Pubmed = {2831956}, Title = {Pyrene phospholipid as a biological fluorescent probe for studying fusion of virus membrane with liposomes}, Uuid = {2BD2D776-EE2C-11DA-8605-000D9346EC2A}, Volume = {27}, Year = {1988}} @article{Palma:2004, Abstract = {Stem cells are crucial for normal development and homeostasis, and their misbehavior may be related to the origin of cancer. Progress in these areas has been difficult because the mechanisms regulating stem cell lineages are not well understood. Here, we have investigated the role of the SHH-GLI pathway in the developing mouse neocortex. The results show that SHH signaling endogenously regulates the number of embryonic and postnatal mouse neocortical cells with stem cell properties, and controls precursor proliferation in a concentration-dependent manner in cooperation with EGF signaling. These findings identify a crucial mechanism for the regulation of the number of cells with stem cell properties that is unexpectedly conserved in different stem cell niches.}, Author = {Palma, Veronica and Ruiz i Altaba, Ariel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {10 Development;Signal Transduction;Animals;Transcription Factors;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Trans-Activators;Mice, Mutant Strains;Phenotype;Neocortex;Mice, Inbred C57BL;Research Support, U.S. Gov't, P.H.S.;Mice, Knockout;Epidermal Growth Factor;Mice;Cell Division;22 Stem cells;Stem Cells;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {8701744}, Number = {2}, Organization = {The Skirball Institute and Department of Cell Biology, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA.}, Pages = {337-45}, Pii = {dev.00930}, Pubmed = {14681189}, Title = {Hedgehog-GLI signaling regulates the behavior of cells with stem cell properties in the developing neocortex}, Uuid = {A80346D0-7B39-424C-996C-E5BE181816E6}, Volume = {131}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.00930}} @article{Palma:2005, Abstract = {Sonic hedgehog (Shh) signaling controls many aspects of ontogeny, orchestrating congruent growth and patterning. During brain development, Shh regulates early ventral patterning while later on it is critical for the regulation of precursor proliferation in the dorsal brain, namely in the neocortex, tectum and cerebellum. We have recently shown that Shh also controls the behavior of cells with stem cell properties in the mouse embryonic neocortex, and additional studies have implicated it in the control of cell proliferation in the adult ventral forebrain and in the hippocampus. However, it remains unclear whether it regulates adult stem cell lineages in an equivalent manner. Similarly, it is not known which cells respond to Shh signaling in stem cell niches. Here we demonstrate that Shh is required for cell proliferation in the mouse forebrain's subventricular zone (SVZ) stem cell niche and for the production of new olfactory interneurons in vivo. We identify two populations of Gli1(+) Shh signaling responding cells: GFAP(+) SVZ stem cells and GFAP(-) precursors. Consistently, we show that Shh regulates the self-renewal of neurosphere-forming stem cells and that it modulates proliferation of SVZ lineages by acting as a mitogen in cooperation with epidermal growth factor (EGF). Together, our data demonstrate a critical and conserved role of Shh signaling in the regulation of stem cell lineages in the adult mammalian brain, highlight the subventricular stem cell astrocytes and their more abundant derived precursors as in vivo targets of Shh signaling, and demonstrate the requirement for Shh signaling in postnatal and adult neurogenesis.}, Author = {Palma, Ver{\'o}nica and Lim, Daniel A. and Dahmane, Nadia and S{\'a}nchez, Pilar and Brionne, Thomas C. and Herzberg, Claudia D. and Gitton, Yorick and Carleton, Alan and Alvarez-Buylla, Arturo and Altaba, Ariel Ruiz I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {04 Adult neurogenesis factors}, Month = {1}, Nlm_Id = {8701744}, Number = {2}, Organization = {The Skirball Institute, NYU School of Medicine, 540 First Avenue, New York, NY 10016, USA.}, Pages = {335-44}, Pii = {dev.01567}, Pubmed = {15604099}, Title = {Sonic hedgehog controls stem cell behavior in the postnatal and adult brain}, Uuid = {1B9B5223-93BC-46C1-B2D2-0AA256B085BF}, Volume = {132}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.01567}} @article{Palmer:2006, Abstract = {ABSTRACT: BACKGROUND: Cell-based microarrays were first described by Ziauddin and Sabatini in 2001 as a powerful new approach for performing high throughput screens of gene function. An important application of cell-based microarrays is in screening for proteins that modulate gene networks. To this end, cells are grown over the surface of arrays of RNAi or expression reagents. Cells growing in the immediate vicinity of the arrayed reagents are transfected and the arrays can then be scanned for cells showing localised changes in function. Here we describe the construction of a large-scale microarray using expression plasmids containing human genes, its use in screening for genes that induce apoptosis when over-expressed and the characterisation of a number of these genes by following the transcriptional response of cell cultures during their induction of apoptosis. RESULTS: High-density cell-based arrays were successfully fabricated using 1,959 un-tagged open reading frames (ORFs) taken from the Mammalian Gene Collection (MGC) in mammalian expression vectors. The arrays were then used to screen for genes inducing apoptosis in Human Embryonic Kidney (HEK293T) cells. Using this approach, 10 genes were clearly identified and confirmed to induce apoptosis. Some of these genes have previously been linked to apoptosis, others not. The mechanism of action of three of the 10 genes were then characterised further by following the transcriptional events associated with apoptosis induction using expression profiling microarrays. This data demonstrates a clear pro-apoptotic transcriptional response in cells undergoing apoptosis and also suggests the use of common apoptotic pathways regardless of the nature of the over-expressed protein triggering cell death. CONCLUSIONS: This study reports the design and use of the first truly large-scale cell-based microarrays for over-expression studies. Ten genes were confirmed to induce apoptosis, some of which were not previously known to possess this activity. Transcriptome analysis on three of the 10 genes demonstrated their use of similar pathways to invoke apoptosis.}, Author = {Palmer, and Miller, and Freeman,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {1471-2164}, Journal = {BMC Genomics}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {100965258}, Number = {1}, Pages = {145}, Pii = {1471-2164-7-145}, Pubmed = {16768789}, Title = {Identification and characterisation of human apoptosis inducing proteins using cell-based transfection microarrays and expression analysis}, Uuid = {E872A026-0CBF-4C73-8158-B72D4E33C9B4}, Volume = {7}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1471-2164-7-145}} @article{Palmer:2000, Abstract = {The thin lamina between the hippocampal hilus and granule cell layer, or subgranule zone (SGZ), is an area of active proliferation within the adult hippocampus known to generate new neurons throughout adult life. Although the neuronal fate of many dividing cells is well documented, little information is available about the phenotypes of cells in S- phase or how the dividing cells might interact with neighboring cells in the process of neurogenesis. Here, we make the unexpected observation that dividing cells are found in dense clusters associated with the vasculature and roughly 37\%of all dividing cells are immunoreactive for endothelial markers. Most of the newborn endothelial cells disappear over several weeks, suggesting that neurogenesis is intimately associated with a process of active vascular recruitment and subsequent remodeling. The present data provide the first evidence that adult neurogenesis occurs within an angiogenic niche. This environment may provide a novel interface where mesenchyme-derived cells and circulating factors influence plasticity in the adult central nervous system.}, Author = {Palmer, T. D. and Willhoite, A. R. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Comp Neurol}, Keywords = {Cell Survival;Rats/*physiology;BB;Neurons/*cytology/physiology;Aging/physiology;Female;Endothelium, Vascular/cytology;02 Adult neurogenesis migration;Animal;Capillaries/physiology;Stem Cells/cytology/metabolism;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;Rats, Inbred F344;Animals, Newborn;Neuroglia/physiology;Intermediate Filament Proteins/metabolism;Hippocampus/*blood supply/*cytology;Support, U.S. Gov't, P.H.S.;Cell Division;S Phase;Cell Aggregation/physiology;Bromodeoxyuridine;Blood Vessels/cytology/physiology;Neovascularization, Physiologic/physiology}, Number = {4}, Organization = {Stanford University, Department of Neurosurgery, Palo Alto, California 94305, USA. tpalmer\@stanford.edu}, Pages = {479-94.}, Title = {Vascular niche for adult hippocampal neurogenesis}, Uuid = {C6417E5B-D2FA-4877-84CB-88CD177213F6}, Volume = {425}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10975875}} @article{Palmer:1999, Abstract = {During development of the mammalian brain, both neurons and glia are generated from multipotent neural stem cells. Although neurogenesis ceases in most areas at birth, stem cells continue to generate neurons within the subventricular zone and hippocampal dentate gyrus throughout adult life. In this work, we provide the first demonstration that precursors native to regions of the adult brain that generate only glia can also generate neurons after exposure to FGF-2 in vitro. When progenitors isolated from hippocampal tissue were directly compared with cells isolated from the neocortex, both populations were able to initiate a program of proliferative neurogenesis. Genetic marking and lineage analysis showed that a majority of the cells able to generate neurons were multipotent precursors; however, progeny from these precursors acquired the competence to differentiate into neurons only after exposure to FGF-2. The recruitment of similar FGF-2-responsive cells from the adult optic nerve, a structure well isolated from the neurogenic zones within the brain, confirmed that neuron-competent precursors naturally exist in widely divergent tissues of the adult brain.}, Author = {Palmer, T. D. and Markakis, E. A. and Willhoite, A. R. and Safar, F. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Cells, Cultured;Rats;Female;Animal;Stem Cells/*cytology/drug effects;C abstr;Nerve Tissue Proteins/analysis;Male;Fibroblast Growth Factor, Basic/*pharmacology;Neuroglia/*cytology/drug effects;Rats, Inbred F344;Support, Non-U.S. Gov't;Organ Specificity;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Biological Markers/analysis;Hippocampus/*cytology;Neurons/*cytology/drug effects;Brain/*cytology/physiology}, Number = {19}, Organization = {The Salk Institute, Laboratory of Genetics, La Jolla, California 92037, USA.}, Pages = {8487-97.}, Title = {Fibroblast growth factor-2 activates a latent neurogenic program in neural stem cells from diverse regions of the adult CNS}, Uuid = {EE62F486-9D54-466B-B51B-29DC7A6D8050}, Volume = {19}, Year = {1999}, url = {papers/Palmer_JNeurosci1999.pdf}} @article{Palmer:1995, Abstract = {Neurogenesis is restricted to discrete germinal zones within the developing and the adult central nervous systems. With few exceptions, cells that migrate away from these zones and into the parenchyma no longer participate in the generation of new neurons. In this work, we have found that basic fibroblast growth factor is able to stimulate the proliferation of neuronal and glial progenitors isolated from the septum and striatum of adult rats. These progenitors are indistinguishable from those isolated from the adult hippocampus and subventricular zone, two regions that generate neurons well into adult life. Although a variety of cell types are initially isolated from each brain region, the progenitor-like cells from all four regions are capable of considerable proliferation and, with limited serial passage, can be cultured as enriched populations of immature cells that are capable of differentiating into mature glia and neurons following density arrest and growth factor withdrawal. The fact that cells isolated from the septum and striatum proliferate and have the ability to differentiate into neurons once they are removed from their local environment indicates that neurogenesis may be restricted to discrete areas of the developing and the adult brain by regional differences in regulatory signals rather than from an absence of progenitors capable of responding to neurogenic cues.}, Author = {Palmer, T. D. and Ray, J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {Fibroblast Growth Factor, Basic/*pharmacology;Fluorescence;Rats, Inbred F344;Brain/*metabolism;Rats;Female;Immunohistochemistry;Time Factors;Animal;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Cells, Cultured;Neurons/*drug effects;Neuroglia/drug effects;C abstr;Support, Non-U.S. Gov't}, Number = {5}, Organization = {Laboratory of Genetics, Salk Institute, La Jolla, California 92037, USA, tpalmer\@salk.edu}, Pages = {474-86.}, Title = {FGF-2-responsive neuronal progenitors reside in proliferative and quiescent regions of the adult rodent brain}, Uuid = {B16E1CCB-7A05-4001-8958-B4314A40FCD2}, Volume = {6}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8581317}} @article{Palmer:1997, Abstract = {Adult-derived hippocampal progenitors generate neurons, astrocytes, and oligodendrocytes in vitro and following grafting into the adult brain. Although these progenitors have a considerable capacity for in vitro self renewal, it is not known if each lineage is generated by separate committed precursors or by multipotent stem cells. By genetic marking, we have followed individual cells through the process of proliferative expansion, commitment, and differentiation. All three lineages are generated by single marked cells and the relative proportions of each lineage can be strongly influenced by environmental cues. Differentiation is accompanied by a characteristic progression of lineage-specific markers and can be potentiated by retinoic acid, elevated cyclic AMP, or neurotrophic factors. The ability to genetically mark and clone normal diploid hippocampal progenitors provides the first definitive evidence that multipotent neural stem cells exist outside of the adult striatal subventricular zone and supports the hypothesis that FGF-2-responsive neural stem cells may be broadly distributed in the adult brain. Using Smart Source Parsing}, Author = {Palmer, T. D. and Takahashi, J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {Hippocampus/*cytology/drug effects;Astrocytes/*cytology;Cell Survival/drug effects;Cells, Cultured;Rats;Neurons/*cytology/physiology;Nerve Growth Factors/pharmacology;Cyclic AMP/pharmacology;Female;Glucocorticoids, Synthetic/pharmacology;02 Adult neurogenesis migration;Animal;Oligodendroglia/*cytology;Stem Cells/*cytology;Dexamethasone/pharmacology;BB abstr;03 Adult neurogenesis progenitor source;Cell Line;Rats, Inbred F344;Support, Non-U.S. Gov't;Triiodothyronine/pharmacology;Support, U.S. Gov't, P.H.S.;Retinoids/pharmacology}, Number = {6}, Organization = {Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {389-404}, Title = {The adult rat hippocampus contains primordial neural stem cells}, Uuid = {F21C8354-6875-11DA-A4B6-000D9346EC2A}, Volume = {8}, Year = {1997}, url = {papers/Palmer_MolCellNeurosci1997.pdf}} @article{Palmer:2002, Abstract = {Adult neurogenesis is mediated by immature neural precursors that divide within the residual germinal matrices of the brain. In the paper by in this issue of Neuron, the "cause and effect"of adult neurogenesis takes a major step forward with the description of a vascular signaling network that influences neuronal precursor migration and fate. 0896-6273 Comment Journal Article}, Author = {Palmer, T. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Central Nervous System/*blood supply/cytology/*growth &development;Endothelium, Vascular;02 Adult neurogenesis migration;Adult;Central Nervous System;03 Adult neurogenesis progenitor source;Human;Neovascularization, Physiologic;Neovascularization, Physiologic/*physiology;comment;Animals;Humans;Endothelium, Vascular/cytology/*growth &development/physiology;Male;BB abstr}, Medline = {22082296}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {Stanford University, Department of Neurosurgery, MSLS P309, Mail Code 5487, Stanford, CA 94305, USA.}, Pages = {856-8}, Pii = {S0896627302007389}, Pubmed = {12086632}, Title = {Adult neurogenesis and the vascular Nietzsche}, Uuid = {FE916073-B73F-48F9-8BBE-00C43B757FF2}, Volume = {34}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12086632}} @article{Palmini:1995, Abstract = {Cortical dysplastic lesions (CDyLs) are often associated with severe partial epilepsies. We describe the electrographic counterpart of this high degree of epileptogenicity, manifested by continuous or frequent rhythmic epileptogenic discharges recorded directly from CDyLs during intraoperative electrocorticography (ECoG). These ictal or continuous epileptogenic discharges (I/CEDs) assumed one of the following three patterns: (1) repetitive electrographic seizures, (2) repetitive bursting discharges, or (3) continuous or quasicontinuous rhythmic spiking. One or more of these patterns were present in 23 of 34 patients (67\%) with intractable partial epilepsy associated with CDyLs, and in only 1 of 40 patients (2.5\%) with intractable partial epilepsy associated with other types of structural lesions. I/CEDs were usually spatially restricted, thus contrasting with the more widespread interictal ECoG epileptic activity, and tended to colocalize with the magnetic resonance imaging-defined lesion. Completeness of excision of cortical tissue displaying I/CEDs correlated positively with surgical outcome in patients with medically intractable seizures; i.e., three-fourths of the patients in whom it was entirely excised had favorable surgical outcome; in contrast, uniformly poor outcome was observed in those patients in whom areas containing I/CEDs remained in situ. We conclude that CDyLs are highly and intrinsically epileptogenic, and that intraoperative ECoG identification of this intrinsically epileptogenic dysplastic cortical tissue is crucial to decide the extent of excision for best seizure control.}, Author = {Palmini, A. and Gambardella, A. and Andermann, F. and Dubeau, F. and da Costa, J. C. and Olivier, A. and Tampieri, D. and Gloor, P. and Quesney, F. and Andermann, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:29 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {Epilepsies, Partial;Electroencephalography;10 Development;Treatment Outcome;Adolescent;Adult;Female;Infant;Child, Preschool;10 genetics malformation;Child;Humans;Male;Cerebral Cortex;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {7707449}, Number = {4}, Organization = {Porto Alegre Epilepsy Surgery Program, Hospital Sao Lucas da PUCRS, Porto Alegre, Brazil.}, Pages = {476-87}, Pubmed = {7717684}, Title = {Intrinsic epileptogenicity of human dysplastic cortex as suggested by corticography and surgical results}, Uuid = {67D54861-47E5-41AE-B3C0-3D275F7B6C7A}, Volume = {37}, Year = {1995}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.410370410}} @article{Palmini:1991, Abstract = {Diffuse neuronal migration disorders associated with epilepsy can now be recognized by modern neuroimaging techniques, particularly high-resolution MRI. We report 10 patients with a recently described MRI picture of continuous or generalized band heterotopia underlying the cortical mantle, giving the appearance of a "double cortex." They have epilepsy, and almost all have mental retardation. The epileptic disorder varies in nature and degree of severity. Patients may present with infantile spasms, a Lennox-Gastaut syndrome, or other forms of secondary generalized or multifocal epilepsy. Response to medical treatment is variable. Callosotomy may lead to considerable reduction of drop attacks, present in 60\%. Mental retardation is usually mild or moderate, and only rarely severe. It correlates with the type of epileptic syndrome, and is greater in patients with more disorganized cortex overlying the heterotopia. Recognition of this entity by MRI is important for appropriate diagnosis of the epileptic disorder, planning of therapeutic strategy, and prognosis.}, Author = {Palmini, A. and Andermann, F. and Aicardi, J. and Dulac, O. and Chaves, F. and Ponsot, G. and Pinard, J. M. and Gouti\`{e}res, F. and Livingston, J. and Tampieri, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {Epilepsy;10 Development;research support, non-u.s. gov't;Adolescent;Magnetic Resonance Imaging;Syndrome;Female;Child, Preschool;10 genetics malformation;Child;Neuropsychological Tests;Humans;Cerebral Cortex;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0401060}, Number = {10}, Organization = {Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.}, Pages = {1656-62}, Pubmed = {1922811}, Title = {Diffuse cortical dysplasia, or the 'double cortex' syndrome: the clinical and epileptic spectrum in 10 patients}, Uuid = {588A3357-6196-4CC7-9B67-78876E09A5A0}, Volume = {41}, Year = {1991}} @article{Palmini:2004, Abstract = {BACKGROUND: There have been difficulties in achieving a uniform terminology in the literature regarding issues of classification with respect to focal cortical dysplasias (FCDs) associated with epilepsy. OBJECTIVE:S: To review and refine the current terminology and classification issues of potential clinical relevance to epileptologists, neuroradiologists, and neuropathologists dealing with FCD. METHODS: A panel discussion of epileptologists, neuropathologists, and neuroradiologists with special expertise in FCD was held. RESULTS: The panel proposed 1) a specific terminology for the different types of abnormal cells encountered in the cerebral cortex of patients with FCD; 2) a reappraisal of the different histopathologic abnormalities usually subsumed under the term "microdysgenesis," and suggested that this terminology be abandoned; and 3) a more detailed yet straightforward classification of the various histopathologic features that usually are included under the heterogeneous term of "focal cortical dysplasia." CONCLUSION: The panel hopes that these proposals will stimulate the debate toward more specific clinical, imaging, histopathologic, and prognostic correlations in patients with FCD associated with epilepsy.}, Author = {Palmini, A. and Najm, I. and Avanzini, G. and Babb, T. and Guerrini, R. and Foldvary-Schaefer, N. and Jackson, G. and L{\"u}ders, H. O. and Prayson, R. and Spreafico, R. and Vinters, H. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {1526-632X}, Journal = {Neurology}, Keywords = {Epilepsy;Neurons;Brain Diseases;10 Development;24 Pubmed search results 2008;10 genetics malformation;Terminology as Topic;research support, u.s. gov't, p.h.s.;Humans;Cerebral Cortex;review;Nervous System Malformations}, Month = {3}, Nlm_Id = {0401060}, Number = {6 Suppl 3}, Organization = {Pontificia Universidade Cat{\'o}lica do Rio Grande do Sul, Porto Alegre, Brazil. apalmini\@uol.com.br}, Pages = {S2-8}, Pubmed = {15037671}, Title = {Terminology and classification of the cortical dysplasias}, Uuid = {2263ACA4-E4F3-4F7B-945E-07E1473BDC6C}, Volume = {62}, Year = {2004}} @article{Palop:2007, Abstract = {Neural network dysfunction may play an important role in Alzheimer's disease (AD). Neuronal circuits vulnerable to AD are also affected in human amyloid precursor protein (hAPP) transgenic mice. hAPP mice with high levels of amyloid-beta peptides in the brain develop AD-like abnormalities, including cognitive deficits and depletions of calcium-related proteins in the dentate gyrus, a region critically involved in learning and memory. Here, we report that hAPP mice have spontaneous nonconvulsive seizure activity in cortical and hippocampal networks, which is associated with GABAergic sprouting, enhanced synaptic inhibition, and synaptic plasticity deficits in the dentate gyrus. Many Abeta-induced neuronal alterations could be simulated in nontransgenic mice by excitotoxin challenge and prevented in hAPP mice by blocking overexcitation. Aberrant increases in network excitability and compensatory inhibitory mechanisms in the hippocampus may contribute to Abeta-induced neurological deficits in hAPP mice and, possibly, also in humans with AD.}, Author = {Palop, Jorge J. and Chin, Jeannie and Roberson, Erik D. and Wang, Jun and Thwin, Myo T. and Bien-Ly, Nga and Yoo, Jong and Ho, Kaitlyn O. and Yu, Gui-Qiu Q. and Kreitzer, Anatol and Finkbeiner, Steven and Noebels, Jeffrey L. and Mucke, Lennart}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {gamma-Aminobutyric Acid;Neurotoxins;Animals;Humans;Amyloid beta-Protein;Neural Pathways;Neuronal Plasticity;Synaptic Transmission;Neocortex;Epilepsy;Mice, Transgenic;research support, non-u.s. gov't;Amyloid beta-Protein Precursor;Disease Models, Animal;Alzheimer Disease;Mice, Knockout;21 Neurophysiology;Dentate Gyrus;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Neural Inhibition;Cognition Disorders}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA. jpalop\@gladstone.ucsf.edu}, Pages = {697-711}, Pii = {S0896-6273(07)00570-3}, Pubmed = {17785178}, Title = {Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease}, Uuid = {86428C87-F894-454B-A2A0-23F6FFCD3D0B}, Volume = {55}, Year = {2007}, url = {papers/Palop_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.07.025}} @article{Paludan:2005, Abstract = {CD4+ T cells classically recognize antigens that are endocytosed and processed in lysosomes for presentation on major histocompatibility complex (MHC) class II molecules. Here, endogenous Epstein-Barr virus nuclear antigen 1 (EBNA1) was found to gain access to this pathway by autophagy. On inhibition of lysosomal acidification, EBNA1, the dominant CD4+ T cell antigen of latent Epstein-Barr virus infection, slowly accumulated in cytosolic autophagosomes. In addition, inhibition of autophagy decreased recognition by EBNA1-specific CD4+ T cell clones. Thus, lysosomal processing after autophagy may contribute to MHC class II-restricted surveillance of long-lived endogenous antigens including nuclear proteins relevant to disease.}, Author = {Paludan, Casper and Schmid, Dorothee and Landthaler, Markus and Vockerodt, Martina and Kube, Dieter and Tuschl, Thomas and M{\"u}nz, Christian}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Epstein-Barr Virus Nuclear Antigens;Lysosomes;Proteasome Endopeptidase Complex;Animals;Humans;Transfection;Cell Line, Transformed;15 Retrovirus mechanism;Cell Line, Tumor;B-Lymphocytes;11 Glia;14 Immune;Hydrogen-Ion Concentration;Chloroquine;Microsomes;Cell Line;Autophagy;Phagosomes;Antigen Presentation;CD4-Positive T-Lymphocytes;24 Pubmed search results 2008;Histocompatibility Antigens Class II;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {0404511}, Number = {5709}, Organization = {Laboratory of Viral Immunobiology, Rockefeller University, New York, NY 10021, USA.}, Pages = {593-6}, Pii = {1104904}, Pubmed = {15591165}, Title = {Endogenous MHC class II processing of a viral nuclear antigen after autophagy}, Uuid = {03A6151C-2DB1-49FE-B1B2-1F721123AAA3}, Volume = {307}, Year = {2005}, url = {papers/Paludan_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1104904}} @article{Pan:2001, Abstract = {Transmitter release in neurons is thought to be mediated exclusively by high-voltage-activated (HVA) Ca(2+) channels. However, we now report that, in retinal bipolar cells, low-voltage-activated (LVA) Ca(2+) channels also mediate neurotransmitter release. Bipolar cells are specialized neurons that release neurotransmitter in response to graded depolarizations. Here we show that these cells express T-type Ca(2+) channel subunits and functional LVA Ca(2+) currents sensitive to mibefradil. Activation of these currents results in Ca(2+) influx into presynaptic terminals and exocytosis, which we detected as a capacitance increase in isolated terminals and the appearance of reciprocal currents in retinal slices. The involvement of T-type Ca(2+) channels in bipolar cell transmitter release may contribute to retinal information processing. 0896-6273 Journal Article}, Author = {Pan, Z. H. and Hu, H. J. and Perring, P. and Andrade, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Neuron}, Keywords = {13 Olfactory bulb anatomy;Rats, Long-Evans;Membrane Potentials/drug effects/physiology;Animals;Rats;Neurotransmitters/*metabolism;Exocytosis/physiology;Nimodipine/pharmacology;Chelating Agents/pharmacology;Presynaptic Terminals/metabolism;Mibefradil/pharmacology;Patch-Clamp Techniques;Egtazic Acid/*analogs &derivatives/pharmacology;Cobalt/pharmacology;Calcium Channel Blockers/pharmacology;Calcium/metabolism;Retina/cytology/*metabolism;RNA, Messenger/analysis;Electric Capacitance;Support, U.S. Gov't, P.H.S.;Synaptic Transmission/drug effects/*physiology;I abstr;Calcium Channels, T-Type/genetics/*metabolism}, Number = {1}, Organization = {Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA. zhpan\@med.wayne.edu}, Pages = {89-98}, Pubmed = {11604141}, Title = {T-type Ca(2+) channels mediate neurotransmitter release in retinal bipolar cells}, Uuid = {98EDE59A-2222-4259-8541-BFF5729B77B8}, Volume = {32}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11604141}} @article{Pang:2003, Abstract = {Studies using chronic in vivo BrdU exposure, isolating primitive stem cells, and determining BrdU labeling, indicate that stem cells cycle. BrdU is also incorporated into DNA during damage/repair. DNA, which has incorporated BrdU due to cycle transit is heavier than normal, while the density of DNA with damage/repair incorporation is intermediate. DNA density of purified lineage-rhodamine low (rho(low)) Hoechst low (Ho(low)) stem cells or FDC-P1 cell line cells-was assessed in vitro, after exposure to cytokines and BrdU (cycling model) or cytokines and BrdU with bleomycin to induce strand breaks and hydroxyurea to halt cycle progression (damage/repair model). We determined DNA density using cesium chloride (CsCl) gradients and either fluorometry or dot blot chemiluminesence. DNA from BrdU labeled cycling Lin-rho(lo)Ho(lo) or FDC-P1 cells was heavier than normal DNA, while damage repair DNA had an intermediate density. We then assessed BrdU labeling of Lin-rho(lo)Ho(lo) cells in vivo. We found that 70.9\%of lin-rho(lo)Ho(lo) cells labeled at 5 weeks. DNA density of these cells was low, in the damage/repair range, but similar results were obtained with stem cells, which had proliferated in vivo. Dilution of BrdU in in vitro culture of proliferating FDC-P1 cells also resulted in damage/repair density. We conclude that in vitro BrdU labeling models can distinguish between proliferation and damage/repair, but that we cannot obtain high enough in vivo levels to address this issue. All together, while we cannot absolutely exclude damage/repair as contributing to stem cell BrdU labeling, the data indicate that primitive bone marrow stem cells are probably a cycling population. 0021-9541 Journal Article}, Author = {Pang, L. and Reddy, P. V. and McAuliffe, C. I. and Colvin, G. and Quesenberry, P. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {J Cell Physiol}, Keywords = {Dose-Response Relationship, Drug;Animals;Chlorides/diagnostic use;Hydroxyurea/pharmacology;DNA Repair/drug effects/*genetics;Bleomycin/pharmacology;Hematopoietic Stem Cells/cytology/drug effects/*metabolism;Cesium/diagnostic use;Bromodeoxyuridine/diagnostic use/*metabolism;DNA Damage/drug effects/*genetics;Chromosomes/drug effects/genetics;EE;Cell Line;Cytokines/pharmacology;Cell Cycle/drug effects/*genetics;Support, U.S. Gov't, P.H.S.;Photic Stimulation/adverse effects;Mice;DNA/drug effects/*metabolism}, Number = {2}, Organization = {Cancer Center, University of Massachusetts, Worcester, Massachusetts, USA.}, Pages = {251-60}, Pubmed = {14502565}, Title = {Studies on BrdU labeling of hematopoietic cells: stem cells and cell lines}, Uuid = {F86584E2-CDF0-11D9-B244-000D9346EC2A}, Volume = {197}, Year = {2003}, url = {papers/Pang_JCellPhysiol2003.pdf}} @article{Pang:2001, Abstract = {The frontal cortex is an important brain area for divided attention. Lesions of the lateral agranular frontal cortex in rats disrupt divided attention in a simultaneous temporal processing task. In the present study, the activity of lateral agranular neurons was examined while rats performed a simultaneous temporal processing procedure. Rats were trained to time two stimuli (a light and a tone), each associated with a different fixed interval. Simple trials, in which a single stimulus was presented, and compound trials, in which both stimuli were presented simultaneously, occurred randomly in a session. Rats were able to divide attention between the two stimuli, as assessed by the pattern of lever presses. Approximately 50\%of lateral agranular neurons responded to at least one phase of the task with four response patterns observed. The activity of type 1 cells (60\%) was altered to compound, but not simple, stimuli. Type 2 cells (10\%) responded to both types of simple stimuli and to compound stimuli. Type 3 cells (27\%) had changes in firing rate to one type of simple stimulus and to compound stimuli. Type 4 cells (3\%) responded to one type of simple stimulus, but were unresponsive to all other stimuli.The large proportion of type 1 cells supports the hypothesis that the lateral agranular cortex is important in divided attention. Previous studies have suggested that the lateral agranular cortex in rats is equivalent to the primary motor cortex. If so, the results from the present study provide evidence that the lateral agranular cortex may have some cognitive functions, in addition to being part of the motor system.}, Author = {Pang, K. C. and Yoder, R. M. and Olton, D. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Photic Stimulation;Behavior, Animal;Rats;Rats, Long-Evans;Research Support, U.S. Gov't, P.H.S.;Time Factors;Time Perception;Attention;Acoustic Stimulation;Research Support, U.S. Gov't, Non-P.H.S.;Electrophysiology;Male;Animals;24 Pubmed search results 2008;Neurons;Frontal Lobe}, Medline = {21173253}, Nlm_Id = {7605074}, Number = {3}, Organization = {Department of Psychology and J. P. Scott Center for Neuroscience, Mind and Behavior, Bowling Green State University, Bowling Green, OH 43403, USA. kpang\@bgnet.bgsu.edu}, Pages = {615-28}, Pii = {S0306452201000185}, Pubmed = {11274782}, Title = {Neurons in the lateral agranular frontal cortex have divided attention correlates in a simultaneous temporal processing task}, Uuid = {4263ED18-DEF3-4455-BC21-8B08487C93E0}, Volume = {103}, Year = {2001}} @article{Pannasch:2006, Abstract = {Activation of microglia by LPS leads to an induction of cytokine and NO release, reduced proliferation and increased outward K(+) conductance, the latter involving the activation of Kv1.5 and Kv1.3 channels. We studied the role of these channels for microglial function using two strategies to interfere with channel expression, a Kv1.5 knockout (Kv1.5(-/-)) mouse and an antisense oligonucleotide (AO) approach. The LPS-induced NO release was reduced by AO Kv1.5 and completely absent in the Kv1.5(-/-) animal; the AO Kv1.3 had no effect. In contrast, proliferation was augmented with both, loss of Kv1.3 or Kv1.5 channel expression. After facial nerve lesion, proliferation rate was higher in Kv1.5(-/-) animals as compared to wild type. Patch clamp experiments confirmed the reduction of the LPS-induced outward current amplitude in Kv1.5(-/-) microglia as well as in Kv1.5- or Kv1.3 AO-treated cells. Our study indicates that induction of K(+) channel expression is a prerequisite for the full functional spectrum of microglial activation.}, Author = {Pannasch, and F{\"a}rber, and Nolte, and Blonski, and Yan Chiu, and Messing, and Kettenmann,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9100095}, Number = {4}, Organization = {Cellular Neuroscience, Max-Delbr{\"u}ck-Center for Molecular Medicine, Robert-R{\"o}ssle-Strae 10, 13125 Berlin, Germany.}, Pages = {401-411}, Pii = {S1044-7431(06)00190-4}, Pubmed = {17055293}, Title = {The potassium channels Kv1.5 and Kv1.3 modulate distinct functions of microglia}, Uuid = {18439C4D-44A4-43E9-ABC9-2F2B6D68ACFD}, Volume = {33}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2006.08.009}} @article{Paradis:2007, Abstract = {We report the results of a genetic screen to identify molecules important for synapse formation and/or maintenance. siRNAs were used to decrease the expression of candidate genes in neurons, and synapse development was assessed. We surveyed 22 cadherin family members and demonstrated distinct roles for cadherin-11 and cadherin-13 in synapse development. Our screen also revealed roles for the class 4 Semaphorins Sema4B and Sema4D in the development of glutamatergic and/or GABAergic synapses. We found that Sema4D affects the formation of GABAergic, but not glutamatergic, synapses. Our screen also identified the activity-regulated small GTPase Rem2 as a regulator of synapse development. A known calcium channel modulator, Rem2 may function as part of a homeostatic mechanism that controls synapse number. These experiments establish the feasibility of RNAi screens to characterize the mechanisms that control mammalian neuronal development and to identify components of the genetic program that regulate synapse formation and/or maintenance.}, Author = {Paradis, Suzanne and Harrar, Dana B. and Lin, Yingxi and Koon, Alex C. and Hauser, Jessica L. and Griffith, Eric C. and Zhu, Li and Brass, Lawrence F. and Chen, Chinfei and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Synapses;24 Pubmed search results 2008;research support, non-u.s. gov't;Cadherins;21 Neurophysiology;Monomeric GTP-Binding Proteins;Semaphorins;Nerve Tissue Proteins;RNA Interference;research support, n.i.h., extramural;Molecular Biology;gamma-Aminobutyric Acid;Animals;Glutamic Acid;Humans;Feasibility Studies;RNA, Small Interfering}, Month = {1}, Nlm_Id = {8809320}, Number = {2}, Organization = {Neurobiology Program, Department of Neurology, Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {217-32}, Pii = {S0896-6273(06)00997-4}, Pubmed = {17224404}, Title = {An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development}, Uuid = {BFCF786D-A213-4CED-96A7-20A512DDE186}, Volume = {53}, Year = {2007}, url = {papers/Paradis_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.12.012}} @article{Pardridge:2002, Abstract = {Brain drug development of either small molecule or large molecule (recombinant proteins, gene medicines) neurotherapeutics has been limited, owing to the restrictive transport properties of the brain microvasculature, which forms the blood-brain barrier (BBB) in vivo. Widespread drug delivery to the brain, while not feasible via craniotomy and intracerebral injection, is possible if the drug is delivered to brain via the transvascular route through the BBB. Novel brain drug delivery and drug targeting strategies can be developed from an understanding of the molecular and cellular biology of the brain microvascular and BBB transport processes. 0896-6273 Journal Article Review Review, Tutorial}, Author = {Pardridge, W. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Neuron}, Keywords = {Gene Therapy/*methods;Microcirculation/*drug effects/metabolism;Brain/*blood supply/*drug effects/metabolism;Human;Drug Administration Routes;Endothelium, Vascular/drug effects/metabolism;T;Blood-Brain Barrier/*drug effects/physiology;Carrier Proteins/drug effects/metabolism;Animals;Tight Junctions/drug effects/metabolism;23 Technique;Central Nervous System Diseases/*drug therapy}, Number = {4}, Organization = {Department of Medicine, School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA. wpardridge\@mednet.ucla.edu}, Pages = {555-8}, Title = {Drug and gene delivery to the brain: the vascular route}, Uuid = {D8BFD5C3-DBC3-4BE6-8D50-4CF9803E63CD}, Volume = {36}, Year = {2002}, url = {papers/Pardridge_Neuron2002.pdf}} @article{Paredes:2006, Abstract = {While there are many recent examples of single gene deletions that lead to defects in cortical development, most human cases of cortical disorganization can be attributed to a combination of environmental and genetic factors. Elucidating the cellular or developmental basis of teratogenic exposures in experimental animals is an important approach to understanding how environmental insults at particular developmental junctures can lead to complex brain malformations. Rats with prenatal exposure to methylazoxymethanol (MAM) reproduce many anatomical features seen in epilepsy patients. Previous studies have shown that heterotopic clusters of neocortically derived neurons exhibit hyperexcitable firing activity and may be a source of heightened seizure susceptibility; however, the events that lead to the formation of these abnormal cell clusters is unclear. Here we used a panel of molecular markers and birthdating studies to show that in MAM-exposed rats the abnormal cell clusters (heterotopia) first appear postnatally in the hippocampus (P1-2) and that their appearance is preceded by a distinct sequence of perturbations in neocortical development: 1) disruption of the radial glial scaffolding with premature astroglial differentiation, and 2) thickening of the marginal zone with redistribution of Cajal-Retzius neurons to deeper layers. These initial events are followed by disruption of the cortical plate and appearance of subventricular zone nodules. Finally, we observed the erosion of neocortical subventricular zone nodules into the hippocampus around parturition followed by migration of nodules to hippocampus. We conclude that prenatal MAM exposure disrupts critical developmental processes and prenatal neocortical structures, ultimately resulting in neocortical disorganization and hippocampal malformations.}, Author = {Paredes, Mercedes and Pleasure, Samuel J. and Baraban, Scott C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Pregnancy;Cell Differentiation;Animals;Rats;21 Epilepsy;Female;Epilepsy;Rats, Sprague-Dawley;Hippocampus;Research Support, N.I.H., Intramural;Cell Movement;Cell Proliferation;Disease Models, Animal;Teratogens;Animals, Newborn;Nervous System Malformations;Cerebral Cortex;21 Neurophysiology;Neurons;Neuroglia;Methylazoxymethanol Acetate;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Stem Cells;Choristoma}, Month = {3}, Nlm_Id = {0406041}, Number = {1}, Organization = {Epilepsy Research Laboratory, Department of Neurological Surgery, University of California, San Francisco, San Francisco, California 94143, USA.}, Pages = {133-48}, Pubmed = {16432901}, Title = {Embryonic and early postnatal abnormalities contributing to the development of hippocampal malformations in a rodent model of dysplasia}, Uuid = {722B3FFA-9E72-4A7A-9CB9-F8363F6B54D7}, Volume = {495}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20871}} @article{Paredes:2002, Abstract = {Major advances in the identification of genes expressed in malformation-associated epileptic disorders have been made. Some of these changes reflect the complex gene interactions necessary for proper neurodevelopment, whereas others suggest specific synaptic aberrations that could result in a hyperexcitable, and ultimately, epileptic condition. Here we review reported changes in gene expression associated with a malformed brain, with particular emphasis on how these changes provide clues to seizure genesis.}, Author = {Paredes, Mercedes F. and Baraban, Scott C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0893-7648}, Journal = {Mol Neurobiol}, Keywords = {Cytoskeletal Proteins;Microtubule-Associated Proteins;Animals;Synapses;Gene Expression Regulation, Developmental;Rats;Gene Expression Regulation;Humans;Tuberous Sclerosis;21 Epilepsy;Brain;review;Epilepsy;Mice, Neurologic Mutants;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Cytoskeleton;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {22279197}, Month = {8}, Nlm_Id = {8900963}, Number = {1}, Pages = {109-16}, Pii = {MN:26:1:109}, Pubmed = {12392060}, Title = {A review of gene expression patterns in the malformed brain}, Uuid = {681AD472-548D-4BFA-B8ED-227C8FB205CC}, Volume = {26}, Year = {2002}} @article{Parent:2002, Abstract = {The persistence of neurogenesis in the forebrain subventricular zone (SVZ) of adult mammals suggests that the mature brain maintains the potential for neuronal replacement after injury. We examined whether focal ischemic injury in adult rat would increase SVZ neurogenesis and direct migration and neuronal differentiation of endogenous precursors in damaged regions. Focal stroke was induced in adult rats by 90-minute right middle cerebral artery occlusion (tMCAO). Cell proliferation and neurogenesis were assessed with bromodeoxyuridine (BrdU) labeling and immunostaining for cell type-specific markers. Brains examined 10-21 days after stroke showed markedly increased SVZ neurogenesis and chains of neuroblasts extending from the SVZ to the peri-infarct striatum. Many BrdU-labeled cells persisted in the striatum and cortex adjacent to infarcts, but at 35 days after tMCAO only BrdU-labeled cells in the neostriatum expressed neuronal markers. Newly generated cells in the injured neostriatum expressed markers of medium spiny neurons, which characterize most neostriatal neurons lost after tMCAO. These findings indicate that focal ischemic injury increases SVZ neurogenesis and directs neuroblast migration to sites of damage. Moreover, neuroblasts in the injured neostriatum appear to differentiate into a region-appropriate phenotype, which suggests that the mature brain is capable of replacing some neurons lost after ischemic injury. 0364-5134 Journal Article}, Author = {Parent, J. M. and Vexler, Z. S. and Gong, C. and Derugin, N. and Ferriero, D. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Ann Neurol}, Keywords = {Neurons/*cytology/pathology;Cell Division/physiology;Rats, Sprague-Dawley;Corpus Striatum/*cytology/pathology;Rats;Cerebrovascular Accident/*pathology;Support, U.S. Gov't, P.H.S.;D pdf;Animals;Male;Prosencephalon/*cytology/pathology}, Number = {6}, Organization = {Department of Neurology, University of Michigan Medical Center, 4412 Kresge III, 200 Zina Pitcher Place, Ann Arbor, MI 48109-0585, USA. parent\@umich.edu}, Pages = {802-13}, Title = {Rat forebrain neurogenesis and striatal neuron replacement after focal stroke}, Uuid = {BAA15832-C26D-11DA-969D-000D9346EC2A}, Volume = {52}, Year = {2002}, url = {papers/Parent_AnnNeurol2002.pdf}} @article{Parent:2005, Abstract = {Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures. Ann Neurol 2005.}, Author = {Parent, and Elliott, and Pleasure, and Barbaro, and Lowenstein,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {10 Development;10 Hippocampus;06 Adult neurogenesis injury induced}, Month = {10}, Nlm_Id = {7707449}, Organization = {Department of Neurology, University of Michigan Medical Center, Ann Arbor, MI.}, Pubmed = {16261566}, Title = {Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy}, Uuid = {93266F9B-E499-448A-9F8B-86C357DDFA20}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.20699}} @article{Parent:1997, Abstract = {The dentate granule cell layer of the rodent hippocampal formation has the distinctive property of ongoing neurogenesis that continues throughout adult life. In both human temporal lobe epilepsy and rodent models of limbic epilepsy, this same neuronal population undergoes extensive remodeling, including reorganization of mossy fibers, dispersion of the granule cell layer, and the appearance of granule cells in ectopic locations within the dentate gyrus. The mechanistic basis of these abnormalities, as well as their potential relationship to dentate granule cell neurogenesis, is unknown. We used a systemic chemoconvulsant model of temporal lobe epilepsy and bromodeoxyuridine (BrdU) labeling to investigate the effects of prolonged seizures on dentate granule cell neurogenesis in adult rats, and to examine the contribution of newly differentiated dentate granule cells to the network changes seen in this model. Pilocarpine-induced status epilepticus caused a dramatic and prolonged increase in cell proliferation in the dentate subgranular proliferative zone (SGZ), an area known to contain neuronal precursor cells. Colocalization of BrdU- immunolabeled cells with the neuron-specific markers turned on after division, 64 kDa, class III beta-tubulin, or microtubule-associated protein-2 showed that the vast majority of these mitotically active cells differentiated into neurons in the granule cell layer. Newly generated dentate granule cells also appeared in ectopic locations in the hilus and inner molecular layer of the dentate gyrus. Furthermore, developing granule cells projected axons aberrantly to both the CA3 pyramidal cell region and the dentate inner molecular layer. Induction of hippocampal seizure activity by perforant path stimulation resulted in an increase in SGZ mitotic activity similar to that seen with pilocarpine administration. These observations indicate that prolonged seizure discharges stimulate dentate granule cell neurogenesis, and that hippocampal network plasticity associated with epileptogenesis may arise from aberrant connections formed by newly born dentate granule cells.}, Author = {Parent, J. M. and Yu, T. W. and Leibowitz, R. T. and Geschwind, D. H. and Sloviter, R. S. and Lowenstein, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {J Neurosci}, Keywords = {Pilocarpine;Electric Stimulation;Rats;Neuronal Plasticity/physiology;Neurons/cytology/*physiology;Cell Movement/*physiology;Animal;Rats, Sprague-Dawley;Male;Status Epilepticus/chemically induced/*physiopathology;Support, Non-U.S. Gov't;Cell Division/physiology;Support, U.S. Gov't, P.H.S.;D;Dentate Gyrus/*cytology/physiopathology;Cell Differentiation/physiology;Parasympathomimetics;Bromodeoxyuridine}, Number = {10}, Organization = {Departments of Neurology and Anatomy, University of California, San Francisco, California 94143, USA.}, Pages = {3727-38.}, Title = {Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus}, Uuid = {A217B902-810F-11DA-9009-000D9346EC2A}, Volume = {17}, Year = {1997}, url = {papers/Parent_JNeurosci1997.pdf}} @article{Parent:2002a, Abstract = {Neuronal precursors in the adult rodent forebrain subventricular zone (SVZ) proliferate, migrate to the olfactory bulb in a restricted pathway known as the rostral migratory stream (RMS), and differentiate into neurons. The effects of injury on this neurogenic region of the mature brain are poorly understood. To determine whether seizure- induced injury modulates SVZ neurogenesis, we induced status epilepticus (SE) in adult rats by systemic chemoconvulsant administration and examined patterns of neuronal precursor proliferation and migration in the SVZ-olfactory bulb pathway. Within 1- 2 weeks after pilocarpine-induced SE, bromodeoxyuridine (BrdU) labeling and Nissl staining increased in the rostral forebrain SVZ. These changes were associated with an increase in cells expressing antigenic markers of SVZ neuroblasts 2-3 weeks after prolonged seizures. At these same time points the RMS expanded and contained more proliferating cells and immature neurons. BrdU labeling and stereotactic injections of retroviral reporters into the SVZ showed that prolonged seizures also increased neuroblast migration to the olfactory bulb and induced a portion of the neuronal precursors to exit the RMS prematurely. These findings indicate that SE expands the SVZ neuroblast population and alters neuronal precursor migration in the adult rat forebrain. Identification of the mechanisms underlying the response of neural progenitors to seizure-induced injury may help to advance brain regenerative therapies by using either transplanted or endogenous neural precursor cells.}, Author = {Parent, J. M. and Valentin, V. V. and Lowenstein, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Pilocarpine;Animals;Rats;Neuronal Plasticity;D both;Cell Count;Rats, Sprague-Dawley;Cell Movement;Male;Status Epilepticus;Olfactory Bulb;Research Support, U.S. Gov't, P.H.S.;Prosencephalon;Cerebral Ventricles;Neurons;06 Adult neurogenesis injury induced;Cell Division;24 Pubmed search results 2008;Genes, Reporter;Immunohistochemistry;Stem Cells;Bromodeoxyuridine;Research Support, Non-U.S. Gov't}, Medline = {21940964}, Month = {4}, Nlm_Id = {8102140}, Number = {8}, Organization = {Department of Neurology, University of Michigan Medical Center, Ann Arbor, Michigan 48104, USA. parent\@umich.edu}, Pages = {3174-88.}, Pii = {22/8/3174}, Pubmed = {11943819}, Title = {Prolonged seizures increase proliferating neuroblasts in the adult rat subventricular zone-olfactory bulb pathway}, Uuid = {F4FD0D26-ECDB-11DA-8605-000D9346EC2A}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/20026296}, Bdsk-Url-2 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11943819%20http://www.jneurosci.org/cgi/content/full/22/8/3174%20http://www.jneurosci.org/cgi/content/abstract/22/8/3174}} @article{Parent:2003, Abstract = {The persistence of neurogenesis in the adult mammalian forebrain suggests that endogenous precursors may be a potential source for neuronal replacement after injury or neurodegeneration. Limited knowledge exists, however, regarding the normal function of neurogenesis in the adult and its alteration by brain injury. Neural precursors generate neurons throughout life in the mammalian forebrain subventricular zone (SVZ)-olfactory bulb pathway and hippocampal dentate gyrus. Accumulating evidence indicates that various brain insults increase neurogenesis in these persistent germinative zones. Two brain injury models in particular, experimental epilepsy and stroke in the adult rodent, have provided significant insight into the consequences of injury-induced neurogenesis. Studies of dentate gyrus neurogenesis in adult rodent epilepsy models suggest that seizure-induced neurogenesis involves aberrant neuroblast migration and integration that may contribute to persistent hippocampal hyperexcitability. In contrast, adult rat forebrain SVZ neurogenesis induced by stroke may have reparative effects. SVZ neural precursors migrate to regions of focal or global ischemic injury and appear to form appropriate neuronal subtypes to replace damaged neurons. These findings underscore the need for a better understanding of injury-induced neurogenesis in the adult and suggest that the manipulation of endogenous neural precursors is a potential strategy for brain reparative therapies.}, Author = {Parent, Jack M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {1073-8584}, Journal = {Neuroscientist}, Keywords = {Epilepsy;Cerebrovascular Accident;Cell Differentiation;Research Support, Non-U.S. Gov't;Brain Injuries;Models, Neurological;Stem Cells;Cell Division;Research Support, U.S. Gov't, P.H.S.;review, tutorial;Humans;Animals;24 Pubmed search results 2008;review;Neurons}, Medline = {22815391}, Month = {8}, Nlm_Id = {9504819}, Number = {4}, Organization = {Department of Neurology, University of Michigan Medical Center, Ann Arbor 48109-0585, USA. parent\@umich.edu}, Pages = {261-72}, Pubmed = {12934709}, Title = {Injury-induced neurogenesis in the adult mammalian brain}, Uuid = {C7FF7B6A-F4B5-499D-8789-2EA5B8468C05}, Volume = {9}, Year = {2003}} @article{Park:2005, Abstract = {Prostate apoptosis response 4 (Par-4) is a leucine zipper containing protein that plays a role in apoptosis. Although Par-4 is expressed in neurons, its physiological role in the nervous system is unknown. Here we identify Par-4 as a regulatory component in dopamine signaling. Par-4 directly interacts with the dopamine D2 receptor (D2DR) via the calmodulin binding motif in the third cytoplasmic loop. Calmodulin can effectively compete with Par-4 binding in a Ca2+-dependent manner, providing a route for Ca2+-mediated downregulation of D2DR efficacy. To examine the importance of the Par-4/D2DR interaction in dopamine signaling in vivo, we used a mutant mouse lacking the D2DR interaction domain of Par-4, Par-4DeltaLZ. Primary neurons from Par-4DeltaLZ embryos exhibit an enhanced dopamine-cAMP-CREB signaling pathway, indicating an impairment in dopamine signaling in these cells. Remarkably, Par-4DeltaLZ mice display significantly increased depression-like behaviors. Collectively, these results provide evidence that Par-4 constitutes a molecular link between impaired dopamine signaling and depression.}, Author = {Park, Sang Ki and Nguyen, Minh Dang and Fischer, Andr{\'e} and Luke, Margaret Po-Shan and Affar, El Bachir l. . B. and Dieffenbach, Paul Brian and Tseng, Huang-Chun C. and Shi, Yang and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {10 Development;Signal Transduction;Animals;Dopamine;Corpus Striatum;Up-Regulation;Mice, Mutant Strains;Cells, Cultured;Apoptosis Regulatory Proteins;Mutation;21 Neurodegenerative;Calcium;Cyclic AMP;Calmodulin;Depression;Cyclic AMP Response Element-Binding Protein;21 Neurophysiology;Neurons;Intracellular Signaling Peptides and Proteins;Receptors, Dopamine D2;Mice;Amino Acid Motifs;24 Pubmed search results 2008;Amino Acid Sequence;Molecular Sequence Data;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {0413066}, Number = {2}, Organization = {Department of Pathology, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.}, Pages = {275-87}, Pii = {S0092-8674(05)00555-6}, Pubmed = {16051151}, Title = {Par-4 links dopamine signaling and depression}, Uuid = {CE5B6A65-4C5E-4FBA-A802-582D6D2101E8}, Volume = {122}, Year = {2005}, url = {papers/Park_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.05.031}} @article{Park:2002, Abstract = {Maternal separation in early life can increase vulnerability to neuropsychiatric disorders over the lifespan. To investigate the effect of acupuncture on cell proliferation in the dentate gyrus (DG), 5-bromo- 2prime prime or minute-deoxyuridine (BrdU)-immunohistochemistry was performed in maternally-separated rat pups. Maternal separation, for 7 days from postnatal day 14, induced a significant decrease of BrdU- immunoreactive cells in DG, while acupuncture treatment at acupoint Shenmen (HT7), at the end of the transverse crease of the ulnar wrist, resulted in the significant increase in the number of BrdU-positive cells in DG. However, acupuncture at acupoint ST36, near the knee joint, produced no increase in the number of BrdU-positive cells. These findings indicate that acupuncture at acupoint HT7 appears to stimulate cell proliferation, and we suggested that acupuncture may be useful in the treatment of diseases related to maternal separation.}, Author = {Park, H. J. and Lim, S. and Lee, H. S. and Lee, H. J. and Yoo, Y. M. and Kim, S. A. and Yin, C. S. and Seo, J. C. and Chung, J. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Neurosci Lett}, Keywords = {D abstr;06 Adult neurogenesis injury induced}, Number = {3}, Organization = {Department of Meridian and Acupuncture, College of Oriental Medicine, Kyung Hee University, 1 Hoegidong, Dongdaemoongu, Seoul, 130-701, South Korea}, Pages = {153-156.}, Title = {Acupuncture enhances cell proliferation in dentate gyrus of maternally- separated rats}, Uuid = {D3ABD3BA-7C30-46BA-A73E-C9149CD22A9D}, Volume = {319}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11834316}} @article{Parnavelas:1991, Abstract = {Neurons of the mammalian cerebral cortex are commonly subdivided into two broad classes: pyramidal and nonpyramidal. The former are projection neurons, while the latter are interneurons. To determine whether the two neuronal classes in the cerebral cortex are derived from the same or separate progenitor cells, we used a recombinant retrovirus containing the reporter gene E-coli beta-galactosidase as a lineage marker. Clonally related neurons expressing the inherited beta-galactosidase gene were detected histochemically, at both light and electron microscopic levels, and their phenotypes were identified using well-established ultrastructural criteria. The clones examined, with one exception, were composed of either all pyramidal or all nonpyramidal neurons. These findings suggest that pyramidal and nonpyramidal neurons in the cerebral cortex have separate lineages and are derived from different progenitor cells in the ventricular zone. This lends weight to the notion that cells in the ventricular zone comprise a heterogeneous population, and that lineage contributes substantially to the phenotype of a neuron.}, Author = {Parnavelas, J. G. and Barfield, J. A. and Franke, E. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Genetic Markers;10 Development;Pregnancy;beta-Galactosidase;Animals;Rats;Phenotype;Female;Telencephalon;Retroviridae;Pyramidal Tracts;03 Adult neurogenesis progenitor source;Research Support, U.S. Gov't, P.H.S.;Histocytochemistry;Escherichia coli;Neurons;Stem Cells;Clone Cells;Research Support, Non-U.S. Gov't}, Medline = {92353586}, Nlm_Id = {9110718}, Number = {6}, Organization = {Department of Anatomy and Developmental Biology, University College London, United Kingdom.}, Pages = {463-8}, Pubmed = {1822752}, Title = {Separate progenitor cells give rise to pyramidal and nonpyramidal neurons in the rat telencephalon}, Uuid = {A791262D-DA3B-41FE-974B-4EC521F099AF}, Volume = {1}, Year = {1991}} @article{Parras:2004, Abstract = {Progenitors in the telencephalic subventricular zone (SVZ) remain mitotically active throughout life, and produce different cell types at embryonic, postnatal and adult stages. Here we show that Mash1, an important proneural gene in the embryonic telencephalon, is broadly expressed in the postnatal SVZ, in progenitors for both neuronal and oligodendrocyte lineages. Moreover, Mash1 is required at birth for the generation of a large fraction of neuronal and oligodendrocyte precursors from the olfactory bulb. Clonal analysis in culture and transplantation experiments in postnatal brain demonstrate that this phenotype reflects a cell-autonomous function of Mash1 in specification of these two lineages. The conservation of Mash1 function in the postnatal SVZ suggests that the same transcription mechanisms operate throughout life to specify cell fates in this structure, and that the profound changes in the cell types produced reflect changes in the signalling environment of the SVZ.}, Author = {Parras, Carlos M. and Galli, Rossella and Britz, Olivier and Soares, Sylvia and Galichet, Christophe and Battiste, James and Johnson, Jane E. and Nakafuku, Masato and Vescovi, Angelo and Guillemot, Fran\c{c}ois}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0261-4189}, Journal = {EMBO J}, Keywords = {01 Adult neurogenesis general}, Month = {11}, Nlm_Id = {8208664}, Number = {22}, Organization = {[1] Institut de G{\'e}n{\'e}tique et de Biologie Cellulaire et Mol{\'e}culaire, Illkirch, France [2] Division of Molecular Neurobiology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK.}, Pages = {4495-505}, Pii = {7600447}, Pubmed = {15496983}, Title = {Mash1 specifies neurons and oligodendrocytes in the postnatal brain}, Uuid = {E4459008-1729-4858-BC1F-FE4F5B26F8CB}, Volume = {23}, Year = {2004}, url = {papers/Parras_EMBOJ2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.emboj.7600447}} @article{Pasquale:2005, Abstract = {Eph receptor tyrosine kinases mould the behaviour of many cell types by binding membrane-anchored ligands, ephrins, at sites of cell-cell contact. Eph signals affect both of the contacting cells and can produce diverse biological responses. New models explain how quantitative variations in the densities and signalling abilities of Eph receptors and ephrins could account for the different effects that are elicited on axon guidance, cell adhesion and cell migration during development, homeostasis and disease.}, Author = {Pasquale, Elena B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1471-0072}, Journal = {Nat Rev Mol Cell Biol}, Keywords = {10 Development;Cell Differentiation;Signal Transduction;Animals;Humans;Protein Binding;Ephrins;review;Cell Membrane;Cell Movement;Cell Proliferation;10 circuit formation;Cell Adhesion;research support, u.s. gov't, p.h.s.;Neurons;research support, n.i.h., extramural;24 Pubmed search results 2008;Cell Physiology;Receptor, EphA1;research support, u.s. gov't, non-p.h.s.}, Month = {6}, Nlm_Id = {100962782}, Number = {6}, Organization = {The Burnham Institute, 10901 N. Torrey Pines Road, La Jolla, California 92037, USA. elenap\@burnham.org}, Pages = {462-75}, Pii = {nrm1662}, Pubmed = {15928710}, Title = {Eph receptor signalling casts a wide net on cell behaviour}, Uuid = {B71A3827-3B20-4D38-A574-6A2AC5B46F0F}, Volume = {6}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrm1662}} @article{Pastorino:2001, Abstract = {The goal of this project was to develop a novel gene transfer system based on macrophages (Mphi) as shuttles of recombinant retroviral vectors carrying therapeutic or marker genes. The murine Mphi cell line WGL5 was used as a source of Mphi for this study. We generated retrovirus-producing Mphi by transducing the WGL5 cells with a replication-defective retroviral vector carrying the enhanced green fluorescent protein (EGFP) reporter gene and the Moloney murine leukemia virus (MoMLV) as helper virus. We demonstrated stable integration of the recombinant retrovirus in the Mphi genome, efficient recombinant retrovirus production, and EGFP gene delivery to different cell lines in vitro. To evaluate Mphi-mediated EGFP gene transfer in vivo, allogeneic mice were injected s.c. with the retrovirus-producing WGL5 Mphi, that gave rise to solid tumor masses at the injection site, highly infiltrated with host leukocytes. We observed EGFP fluorescence in tumor-infiltrating CD4(+) and CD8(+) host T lymphocytes, providing direct evidence of the ability of engineered Mphi to mediate EGFP gene delivery to host cells in vivo. Moreover, we showed that retrovirus-producing Mphi could home to different organs in vivo following i.v. injection into mice. These data demonstrate that Mphi can be engineered as cellular vehicles for recombinant retroviruses carrying heterologous genes and suggest potential applications of this novel vector system for gene therapy.}, Author = {Pastorino, S. and Massazza, S. and Cilli, M. and Varesio, L. and Bosco, M. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {T-Lymphocytes;Transduction, Genetic;Animals;Macrophages;Retroviridae;11 Glia;Microscopy, Fluorescence;Green Fluorescent Proteins;Genetic Vectors;Cell Line;CD8-Positive T-Lymphocytes;Injections, Subcutaneous;Gene Therapy;Mice;Injections, Intravenous;Luminescent Proteins;CD4-Positive T-Lymphocytes;Research Support, Non-U.S. Gov't}, Medline = {21214791}, Month = {3}, Nlm_Id = {9421525}, Number = {6}, Organization = {Laboratory of Molecular Biology, G Gaslini Institute, Largo G Gaslini 5, 16147, Genova, Italy.}, Pages = {431-41}, Pubmed = {11313821}, Title = {Generation of high-titer retroviral vector-producing macrophages as vehicles for in vivo gene transfer}, Uuid = {6BA486A8-60B1-4D5C-977D-B713E351F911}, Volume = {8}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301405}} @article{Patel:2004, Abstract = {There is a high correlation between pediatric epilepsies and neuronal migration disorders. What remains unclear is whether there are intrinsic features of the individual dysplastic cells that give rise to heightened seizure susceptibility, or whether these dysplastic cells contribute to seizure activity by establishing abnormal circuits that alter the balance of inhibition and excitation. Mice lacking a functional p35 gene provide an ideal model in which to address these questions, because these knock-out animals not only exhibit aberrant neuronal migration but also demonstrate spontaneous seizures. Extracellular field recordings from hippocampal slices, characterizing the input-output relationship in the dentate, revealed little difference between wild-type and knock-out mice under both normal and elevated extracellular potassium conditions. However, in the presence of the GABA(A) antagonist bicuculline, p35 knock-out slices, but not wild-type slices, exhibited prolonged depolarizations in response to stimulation of the perforant path. There were no significant differences in the intrinsic properties of dentate granule cells (i.e., input resistance, time constant, action potential generation) from wild-type versus knock-out mice. However, antidromic activation (mossy fiber stimulation) evoked an excitatory synaptic response in over 65\%of granule cells from p35 knock-out slices that was never observed in wild-type slices. Ultrastructural analyses identified morphological substrates for this aberrant excitation: recurrent axon collaterals, abnormal basal dendrites, and mossy fiber terminals forming synapses onto the spines of neighboring granule cells. These studies suggest that granule cells in p35 knock-out mice contribute to seizure activity by forming an abnormal excitatory feedback circuit.}, Author = {Patel, Leena S. and Wenzel, H. J{\"u}rgen and Schwartzkroin, Philip A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {in vitro;Electric Stimulation;Feedback, Biochemical;Evoked Potentials;Animals;Epilepsy;Hippocampus;21 Dysplasia-heterotopia;Bicuculline;Genetic Predisposition to Disease;Dendrites;Mossy Fibers, Hippocampal;Mice, Knockout;21 Neurophysiology;Dentate Gyrus;research support, u.s. gov't, p.h.s.;Neurons;Mice;24 Pubmed search results 2008;Nerve Tissue Proteins;Excitatory Postsynaptic Potentials}, Month = {10}, Nlm_Id = {8102140}, Number = {41}, Organization = {Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA.}, Pages = {9005-14}, Pii = {24/41/9005}, Pubmed = {15483119}, Title = {Physiological and morphological characterization of dentate granule cells in the p35 knock-out mouse hippocampus: evidence for an epileptic circuit}, Uuid = {FE1A8373-F075-4931-B00D-ABD6A847A136}, Volume = {24}, Year = {2004}, url = {papers/Patel_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2943-04.2004}} @article{Paton:1985, Abstract = {Thymidine autoradiography and retrograde transport of horseradish peroxidase (HRP) were combined to determine the connectivity of neurons born in adult canary forebrain. Adult male and female canaries were pretreated with [3H]thymidine to label cells undergoing DNA synthesis prior to mitosis. Thirty or 60 days later, neurons in a forebrain nucleus, hyperstriatium ventralis, pars caudalis (HVc), were labeled by retrograde transport of HRP injected into the only two nuclei known to receive a projection from HVc: robustus archistriatalis (RA) and area X of lobus parolfactorius. The birds were then killed and brain sections were treated to visualize cells containing HRP; these sections were processed for autoradiography to detect [3H]thymidine-labeled cells in the same tissue. More than 9\%of all neurons in HVc were thymidine labeled; but of the almost 20,000 HRP-labeled projection neurons examined, fewer than 20 (0.1\%) were labeled by the thymidine treatment. Furthermore, the median cell body size for area X-projecting cells was significantly larger than that of thymidine-labeled cells, and the median size of thymidine-labeled cells was significantly larger than that of RA-projecting cells. The simplest interpretation of these results is that the new neurons incorporated into nucleus HVc in adult canary brain are local interneurons, intermediate in size between neurons projecting to RA and area X.}, Author = {Paton, J. A. and O'Loughlin, B. E. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Neurosci}, Keywords = {A;01 Adult neurogenesis general;Axonal Transport;Female;Microscopy, Electron;Autoradiography;Thymidine/metabolism;Horseradish Peroxidase/metabolism;Animal;Neurons/*cytology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;DNA Replication;Male;Birds/*anatomy &histology;Brain/*cytology}, Number = {11}, Pages = {3088-93.}, Title = {Cells born in adult canary forebrain are local interneurons}, Uuid = {8D5F85F2-13E7-4CA1-AC9A-6B88C62868E8}, Volume = {5}, Year = {1985}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2414419}} @article{Patrizio:2001, Abstract = {We have studied the modulation of cyclic AMP (cAMP) accumulation by the human immunodeficiency virus type 1 (HIV 1) protein Tat in microglia and astrocyte cultures obtained from neonatal rat brain. Pretreatment of microglia with recombinant Tat resulted in a dose- and time-dependent decrease of cAMP accumulation induced by subsequent exposure to isoproterenol (1 microM). The inhibitory action of 100 ng/mL Tat approached 50\%after 4 h of preincubation and reached a maximum of 70\%after 24 h. The Tat-induced time- and dose-dependent decrease of cAMP accumulation was observed also when microglial cultures were stimulated with the adenylyl cyclase activator forskolin (100 microM). In both cases, Tat inhibitory action was 70\%reverted by a specific monoclonal anti-Tat antibody, but was not prevented either by the phosphodiesterase inhibitor 3-isobutyl-1-methyl-xantine (100 microM) or by a 16-h pretreatment of microglial cultures with the Gi protein inhibitor pertussis toxin (10 ng/mL). All these results suggested that the viral protein acts at a step of the cAMP transduction pathway other than receptors, G proteins and phosphodiesterases. The target of Tat appeared to be adenylyl cyclase, whose activity was markedly reduced (up to 60\%) in membranes prepared from Tat-treated microglial cells, both in basal conditions and after stimulation with isoproterenol and forskolin. The inability of the competitive inhibitor of nitric oxide synthase N(G)-monometyl- L-arginine (20 and 200 microM) to revert Tat action on forskolin-induced cAMP accumulation, and of two potent nitric oxide donors, PAPA and DETA (0.1-2 m M), to alter forskolin-induced cAMP accumulation, excluded an involvement of nitric oxide in Tat-induced adenylyl cyclase inhibition. On the contrary, two inhibitors of nuclear factor kappaB activation, N-tosyl-( L)-phenylalanine chloromethyl ketone (10 microM) and SN50 (25 microM), markedly prevented the reduction of forskolin-evoked cAMP accumulation by Tat, suggesting a possible role for this nuclear transcriptional factor in the regulation of adenylyl cyclase by Tat in microglia. This assumption was strengthened by the ability of lipopolysaccharide (100 ng/mL, 4 h) to mimic the inhibitory effect of the viral protein. Conversely, astrocyte cAMP accumulation was unaffected by the viral protein, as tested at various concentrations and time points. Finally, Tat inhibition of microglial adenylyl cyclase was not due to non-specific cytotoxicity. As cAMP has been reported to exert a neuroprotective role in several in vivo and in vitro models of brain pathologies, and microglia is believed to mediate Tat-induced neurotoxicity, these results suggest that the ability of Tat to inhibit cAMP synthesis in microglia may contribute to neuronal degeneration and cell death associated with HIV infection.}, Author = {Patrizio, M. and Colucci, M. and Levi, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Tosylphenylalanyl Chloromethyl Ketone;Apoptosis;Energy Metabolism;Enzyme Activation;NF-kappa B;GTP-Binding Protein alpha Subunits, Gi-Go;Forskolin;Hydrazines;Antibodies, Monoclonal;Second Messenger Systems;Peptides;Nerve Degeneration;Lipopolysaccharides;Animals;Cyclic AMP;Pertussis Toxin;Cells, Cultured;Isoproterenol;Adenylate Cyclase Toxin;Nitric-Oxide Synthase;Adenylate Cyclase;Gene Products, tat;11 Glia;1-Methyl-3-isobutylxanthine;Virulence Factors, Bordetella;Cell Membrane;Nitric Oxide;Rats;HIV-1;Microglia;Recombinant Fusion Proteins;Arginine;Research Support, Non-U.S. Gov't;Rats, Wistar;Nitroso Compounds;Astrocytes;Nitric Oxide Donors}, Medline = {21210796}, Month = {4}, Nlm_Id = {2985190R}, Number = {2}, Organization = {Neurobiology Section, Laboratory of Pathophysiology, Istituto Superiore di Sanit\`{a}, Rome, Italy. patrizio\@iss.it}, Pages = {399-407}, Pubmed = {11299302}, Title = {Human immunodeficiency virus type 1 Tat protein decreases cyclic AMP synthesis in rat microglia cultures}, Uuid = {8E7D330B-D254-4053-A2ED-CD06B1EC0A52}, Volume = {77}, Year = {2001}, url = {papers/Patrizio_JNeurochem2001.pdf}} @article{Patrylo:2006, Abstract = {PURPOSE: Seizures are observed frequently in humans with diffuse neuronal migration disorders. The reeler mutant mouse also exhibits a diffuse disruption of migration, yet no pro-epileptic phenotype has been reported for this model. Whether this disparity reflects a phenotypic difference that can be used to delineate the mechanisms associated with increasing seizure susceptibility or reflects a paucity of knowledge is unclear. Consequently, this study examined whether seizure susceptibility is altered in reeler mutant mice. METHODS: In vivo (minimal electroshock delivered transcorneally) and in vitro techniques (field-potential recordings in neocortical and hippocampal brain slice preparations exposed to bicuculline methiodide) were used to determine whether the susceptibility to epileptiform activity is enhanced in reeler homozygous mice relative to controls. Adult (3-7 months) male reeler homozygotes (rl/rl) and controls (+/?) were identified based on their behavioral phenotype and were used in all experiments. RESULTS: Minimal electroshock revealed that rl/rl mice, compared with controls, exhibited a lower threshold for electroshock-induced seizures (4.5 +/- 0.52 vs. 6.7 +/- 0.35 mA), and a higher incidence of behavioral seizures (median seizure score, class 4 vs. class 0) when animals were subjected to a 5-mA electroshock stimulus. Additionally, neocortical and hippocampal slices from rl/rl mice were more likely to generate spontaneous epileptiform activity after bicuculline application, compared with controls, and the duration of the epileptiform events elicited in 10-30 muM bicuculline was longer in slices from rl/rl mice. CONCLUSIONS: These data demonstrate that rl/rl mice have enhanced seizure susceptibility that is in part intrinsic to the malformed neocortex and hippocampus. Thus in contrast to prior belief, most animal models of diffuse neuronal migration disorders do exhibit a pro-epileptic phenotype.}, Author = {Patrylo, Peter R. and Browning, Ronald A. and Cranick, Scott}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:54 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {10 Development;Animals;Humans;Phenotype;Neocortex;Epilepsy;Hippocampus;Mice, Neurologic Mutants;Electroshock;research support, non-u.s. gov't;Bicuculline;Genetic Predisposition to Disease;Disease Models, Animal;Male;Nervous System Malformations;Homozygote;10 genetics malformation;Mice;24 Pubmed search results 2008;Kindling, Neurologic;in vitro}, Month = {2}, Nlm_Id = {2983306R}, Number = {2}, Organization = {Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901, U.S.A. ppatrylo\@siumed.edu}, Pages = {257-66}, Pii = {EPI417}, Pubmed = {16499749}, Title = {Reeler homozygous mice exhibit enhanced susceptibility to epileptiform activity}, Uuid = {CCAF4142-4B06-4233-A7CF-1721C1543F6C}, Volume = {47}, Year = {2006}, url = {papers/Patrylo_Epilepsia2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1528-1167.2006.00417.x}} @article{Patten:2006, Abstract = {Signaling by the Notch1 receptor is critical for the formation of radial glia in the developing nervous system. We have shown previously that Notch1 regulates the molecular and morphological differentiation of radial glia through the transcriptional activation of at least two genes, brain lipid binding protein (BLBP) and the erbB2 receptor tyrosine kinase. However, the mechanisms by which this occurs remained undefined. Here we demonstrate that Notch1 effects on radial glia gene expression are mediated by two downstream mechanisms, one that the depends on Suppressor of Hairless [Su(H)] and the other on Deltex1 (DTX1). These two Notch1-binding proteins contribute to the regulation of BLBP and erbB2 expression, respectively. Importantly, our results suggest that, although these events can occur simultaneously, a hierarchical relationship might exist between DTX1 and Su(H), because overexpression of DTX1 or a dominant-negative form of this protein inhibits Su(H)-mediated events but not vice versa. In contrast to the effects of DTX1 overexpression, interference RNA-mediated knock-down of DTX1 blocks Notch1-induced erbB2 promoter activation and radial glia formation selectively, without affecting Su(H)-dependent pathways, indicating that loss of DTX1 expression and expression of dominant-negative DTX1 result in different alterations in cell differentiation and gene expression. Together, these results show that Notch1 regulates radial glia formation through two distinct transcriptional mechanisms and that the outcomes of Notch1 signaling may depend on the relative expression levels of its coregulators.}, Author = {Patten, Brooke A. and Sardi, S. Pablo and Koirala, Samir and Nakafuku, Masato and Corfas, Gabriel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Rats, Long-Evans;Signal Transduction;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Rats;Receptor, erbB-2;Up-Regulation;Animals;Transcription Factors;RNA Interference;Receptor, Notch1;Animals, Newborn;Neuroglia;Down-Regulation;Mice;Promoter Regions (Genetics);24 Pubmed search results 2008;Central Nervous System;Research Support, N.I.H., Extramural;Drosophila Proteins;Repressor Proteins;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {8102140}, Number = {12}, Organization = {Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {3102-8}, Pii = {26/12/3102}, Pubmed = {16554461}, Title = {Notch1 signaling regulates radial glia differentiation through multiple transcriptional mechanisms}, Uuid = {69AF85CE-326D-4C11-8858-A50542E9C448}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4829-05.2006}} @article{Pautot:2008, Abstract = {A central challenge in neuroscience is to understand the formation and function of three-dimensional (3D) neuronal networks. In vitro studies have been mainly limited to measurements of small numbers of neurons connected in two dimensions. Here we demonstrate the use of colloids as moveable supports for neuronal growth, maturation, transfection and manipulation, where the colloids serve as guides for the assembly of controlled 3D, millimeter-sized neuronal networks. Process growth can be guided into layered connectivity with a density similar to what is found in vivo. The colloidal superstructures are optically transparent, enabling remote stimulation and recording of neuronal activity using layer-specific expression of light-activated channels and indicator dyes. The modular approach toward in vitro circuit construction provides a stepping stone for applications ranging from basic neuroscience to neuron-based screening of targeted drugs.}, Author = {Pautot, Sophie and Wyart, Claire and Isacoff, Ehud Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1548-7105}, Journal = {Nat Methods}, Keywords = {Imaging, Three-Dimensional;research support, non-u.s. gov't;Lycopersicon esculentum;Rats;Tissue Engineering;research support, n.i.h., extramural;Nerve Net;Animals;Cells, Cultured;Colloids;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {101215604}, Number = {8}, Organization = {Department of Molecular and Cell Biology, Life Science Addition 271, Mail Code 3200, University of California, Berkeley, USA.}, Pages = {735-40}, Pii = {nmeth.1236}, Pubmed = {18641658}, Title = {Colloid-guided assembly of oriented 3D neuronal networks}, Uuid = {6A0221BE-407C-46CB-828F-ACA7B32850FC}, Volume = {5}, Year = {2008}, url = {papers/Pautot_NatMethods2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth.1236}} @article{Pawelek:2005, Abstract = {Malignant cells express molecular pathways that are also expressed by myeloid cells. Such behaviour is associated with loss of homotypic adhesion between cells, changes in the cellular matrix, induction of angiogenesis, motility, chemotaxis, and several immune-signalling pathways. The overlap between malignant cells and myeloid cells could be explained by one mechanism: fusion of myeloid cells and tumour cells, as noted in animal studies and in two patients with renal-cell carcinoma who underwent bone-marrow transplantation. An overlapping trait in these cells is their glycosylation patterns: hybrids have high expression of N-terminal glycosylation and beta1,6-branched oligosaccharides. In macrophages and cancer cells, these structures have a role in motility and systemic migration; in cancer, they are associated with metastasis and poor prognosis. In addition to myeloid traits, fusion might contribute to aneuploidy and plasticity in cancer. Understanding metastatic cells as myeloid-tumour hybrids suggests new strategies for diagnosis, treatment, and prevention of malignant disease.}, Author = {Pawelek, John M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1470-2045}, Journal = {Lancet Oncol}, Keywords = {11 Glia;22 Stem cells;22 Cancer}, Month = {12}, Nlm_Id = {100957246}, Number = {12}, Organization = {Department of Dermatology and Yale Cancer Center, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520-8059, USA.}, Pages = {988-93}, Pii = {S1470-2045(05)70466-6}, Pubmed = {16321767}, Title = {Tumour-cell fusion as a source of myeloid traits in cancer}, Uuid = {0E56B902-BF8F-11DA-969D-000D9346EC2A}, Volume = {6}, Year = {2005}, url = {papers/Pawelek_LancetOncol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S1470-2045(05)70466-6}} @article{Payankaulam:2008, Abstract = {Quantitative measurements of the Hunchback transcription factor in Drosophila embryos show that its target genes can respond with a high degree of precision to the exact level of the protein, simulating a continuous, analog readout, while other target genes show a combinatorial effect, resembling a Boolean logic element.}, Author = {Payankaulam, Sandhya and Arnosti, David N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {DNA-Binding Proteins;Embryonic Development;Gene Expression Regulation, Developmental;Trans-Activators;Embryo, Nonmammalian;Drosophila Proteins;Evolution, Molecular;Drosophila;Body Patterning;Models, Genetic;Animals;Homeodomain Proteins;24 Pubmed search results 2008;Transcription Factors}, Month = {8}, Nlm_Id = {9107782}, Number = {15}, Organization = {Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan 48824-1319, USA.}, Pages = {R653-R655}, Pii = {S0960-9822(08)00797-5}, Pubmed = {18682204}, Title = {Gene regulation: boundaries within limits}, Uuid = {A97BBE34-1055-424E-8A04-30719C009799}, Volume = {18}, Year = {2008}, url = {papers/Payankaulam_CurrBiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2008.06.040}} @article{Pearson:1993, Abstract = {Retinae of kittens between postnatal (P) days 2 and 10 were examined for the presence of degenerating neuronal profiles, normal nucleoli and microglia. Comparison of the numbers of degenerating profiles with numbers of axons lost from the optic nerve suggest that the majority of these profiles result from the degeneration of retinal ganglion cells. Analysis of local densities of the different profiles revealed different rates of cell loss, occurring at different times in central and peripheral retina. The period of rapid cell loss occurred between P2 and P3 in central retina compared to between P8 and P10 in peripheral retina. At both locations, these periods of rapid cell loss were accompanied by a decrease in the ratio of microglia to dying cells even though the absolute densities of microglia increased. However, calculation of the clearance times of cellular debris indicate that the speed of removal of degeneration products is greater during rapid cell loss, which suggests that cellular degeneration serves to activate the phagocytic process.}, Author = {Pearson, H. E. and Payne, B. R. and Cunningham, T. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Retina;Nerve Degeneration;Cats;Not relevant;Metabolic Clearance Rate;Microglia;Support, U.S. Gov't, P.H.S.;Retinal Ganglion Cells;11 Glia;Animals;Support, Non-U.S. Gov't;Phagocytosis}, Medline = {94199794}, Month = {12}, Nlm_Id = {8908639}, Number = {2}, Organization = {Department of Anatomy and Cell Biology, Temple University School of Medicine, Philadelphia, PA 19140.}, Pages = {249-55}, Pubmed = {8149591}, Title = {Microglial invasion and activation in response to naturally occurring neuronal degeneration in the ganglion cell layer of the postnatal cat retina}, Uuid = {C6C96730-1DA4-424C-B45D-6C5827B2DAC3}, Volume = {76}, Year = {1993}} @article{Pearson:2001, Abstract = {Physiological mapping of the body representation 1 month or longer after forelimb removal in adult rats revealed new pockets of shoulder representation in the forepaw barrel subfield (FBS) in the first somatosensory cortex (SI). These "new" shoulder representations have longer evoked response latencies than sites in the shoulder representation within the trunk subfield, hereafter referred to as the "original" shoulder representation. We postulated that the "new" shoulder representations in the FBS were relayed from the "original" shoulder representation. We investigated this hypothesis by studying anatomical connectivity between the "original" shoulder representation and the FBS in intact control and forelimb deafferented adult rats using Phaseolus vulgaris leucoagglutinin (PHA-L), biocytin, and biotin dextran-amine (BDA) as anterograde tracers. The retrograde tracer cholera toxin beta subunit (CT-B) injected into the FBS was also used to study connectivity between the "original" shoulder representation and the FBS. Using these anatomical tracing techniques, we were unable to show the existence of a direct corticocortical connection between the "original" shoulder representation in the trunk subfield and the FBS in either intact or deafferented rats. Functional connectivity between the two cortical regions was studied by ablating the "original" shoulder representation alone or in combination with the shoulder representation in the second somatosensory cortex (SII) while recording evoked responses in the FBS following electrical stimulation of the shoulder. Both ablations failed to eliminate the evoked responses at the "new" shoulder sites in the FBS, suggesting that SI and SII are not necessary for "new" shoulder input in the FBS. It is suggested that subcortical sites may play a major role in large-scale cortical reorganization. Results of projections from the "original" shoulder representation to parietal medial (PM), parietal lateral (PL), SII, parietal ventral (PV), and parietal rhinal (PR) sensory fields and agranular lateral (AgL) and agranular medial (AgM) motor fields are also described.}, Author = {Pearson, P. P. and Arnold, P. B. and Oladehin, A. and Li, C. X. and Waters, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Fluorescent Dyes;Animals;Lysine;Evoked Potentials;Rats;Neuronal Plasticity;Dextrans;Afferent Pathways;Research Support, U.S. Gov't, Non-P.H.S.;Denervation;Forelimb;Rats, Sprague-Dawley;Axonal Transport;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neurons;Muscle, Skeletal;Somatosensory Cortex;24 Pubmed search results 2008;Biotin;Phytohemagglutinins}, Medline = {21268462}, Month = {5}, Nlm_Id = {0043312}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN 38163, USA.}, Pages = {8-25}, Pubmed = {11374086}, Title = {Large-scale cortical reorganization following forelimb deafferentation in rat does not involve plasticity of intracortical connections}, Uuid = {E1E843FF-925C-4E79-9F80-FBCB6BE1E4EC}, Volume = {138}, Year = {2001}} @article{Pearson:2003, Abstract = {Individual neural progenitors generate different cell types in a reproducible order in the retina, cerebral cortex and probably in the spinal cord. It is unknown how neural progenitors change over time to generate different cell types. It has been proposed that progenitors undergo progressive restriction or transit through distinct competence states; however, the underlying molecular mechanisms remain unclear. Here we investigate neural progenitor competence and temporal identity using an in vivo genetic system--Drosophila neuroblasts--where the Hunchback transcription factor is necessary and sufficient to specify early-born cell types. We show that neuroblasts gradually lose competence to generate early-born fates in response to Hunchback, similar to progressive restriction models, and that competence to acquire early-born fates is present in mitotic precursors but is lost in post-mitotic neurons. These results match those observed in vertebrate systems, and establish Drosophila neuroblasts as a model system for the molecular genetic analysis of neural progenitor competence and plasticity. 1476-4687 Journal Article}, Author = {Pearson, B. J. and Doe, C. Q.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Nature}, Keywords = {Stem Cells/*cytology;Drosophila Proteins/genetics/metabolism;Cell Differentiation;10 Development;F pdf;Phenotype;Neuronal Plasticity;Time Factors;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Drosophila melanogaster/*cytology/embryology/genetics/metabolism;Mitosis;Animals;Support, Non-U.S. Gov't;Transcription Factors/genetics/metabolism;DNA-Binding Proteins/genetics/metabolism;Cell Lineage}, Number = {6958}, Organization = {Institutes of Neuroscience and Molecular Biology, Howard Hughes Medical Institute, University of Oregon 1254, Eugene, Oregon 97403, USA.}, Pages = {624-8}, Pubmed = {14534589}, Title = {Regulation of neuroblast competence in Drosophila}, Uuid = {87218A21-B7AD-4087-ADF5-F63BB64D4EB6}, Volume = {425}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14534589}} @article{Peinado:1993, Abstract = {In the neocortex, as well as in many other brain regions, neurons responding to similar stimulus features are usually found close to one another. Here we examine the possible role of gap junctional communication in forming and defining these local neuronal groupings, examples of which may be the columns found in the neocortex of virtually all mammalian species. We have approached this question experimentally in cortical brain slices using calcium imaging to visualize multicellular activity patterns, and tracer injections to identify the anatomical pattern of gap junction coupling in the developing neocortex. Our results suggest that dendrodendritic gap junctional communication may be involved in the formation of local connectivity, most likely by synchronizing electrical or biochemical activity among neighboring neurons.}, Author = {Peinado, A. and Yuste, R. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Beta;10 Development;21 Neurophysiology;Cell Communication;Human;10 Spiny stellate;review, tutorial;Support, U.S. Gov't, P.H.S.;10 Structural plasticity;Support, Non-U.S. Gov't;Animals;Cerebral Cortex;Neurons;review}, Medline = {94083800}, Nlm_Id = {9110718}, Number = {5}, Organization = {Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461.}, Pages = {488-98}, Pubmed = {8260815}, Title = {Gap junctional communication and the development of local circuits in neocortex}, Uuid = {B58B4F07-7007-48C0-99DB-CB449858841C}, Volume = {3}, Year = {1993}} @article{Peinado:2001, Abstract = {The properties of immature cortex that may enable it to exhibit large-scale wavelike activity during a brief critical developmental period were investigated by imaging neuronal calcium signals in neonatal cortical slices under conditions of artificially enhanced excitability, conditions that produce a more frequent and robust version of the naturally occurring waves. Using pharmacological manipulation to probe the underlying mechanisms, I show that waves can propagate effectively when excitatory synaptic transmission is blocked. In contrast, propagation is very sensitive to reductions in gap junctional communication. In the barrel field cortex wave propagation is affected by the underlying cytoarchitecture in a way that is consistent with a role for dendrodendritic gap junctions. The ability of cortex to sustain wave activity ends around postnatal day 12, precisely when a major reduction in neuronal gap junctions takes place in cortex. These results suggest that in immature cortex gap junctions link neurons into extensive networks that may allow electrical activity to spread over long distances.}, Author = {Peinado, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Excitatory Amino Acid Antagonists;10 Development;Rats, Long-Evans;Electric Conductivity;Electrophysiology;Animals;Rats;10 Structural plasticity;Beta;Neocortex;Vibrissae;Gap Junctions;Giant Cells;Time Factors;Dendrites;Animals, Newborn;10 Spiny stellate;Nerve Net;Neurons;Neurotransmitters;Support, U.S. Gov't, P.H.S.;Somatosensory Cortex;Tetraethylammonium}, Medline = {21104045}, Month = {2}, Nlm_Id = {0375404}, Number = {2}, Organization = {Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York 10461, USA. peinado\@aecom.yu.edu}, Pages = {620-9}, Pubmed = {11160498}, Title = {Immature neocortical neurons exist as extensive syncitial networks linked by dendrodendritic electrical connections}, Uuid = {5342C758-6379-4AFA-BE09-DE0F37DF163A}, Volume = {85}, Year = {2001}, url = {papers/Peinado_JNeurophysiol2001.pdf}} @article{Peinado:2000, Abstract = {Spontaneous neuronal firing during development has the potential to shape many aspects of neuronal wiring throughout the brain. Bursts of electrical activity coordinated among large numbers of neurons, occurring during a brief developmental window, have been described in many regions of the CNS, including retina, hippocampus, and spinal cord, but evidence for this type of activity in developing neocortex has so far been lacking. To identify conditions that may give rise to patterned spontaneous electrical activity in developing neocortex, cholinergic agonists were applied to immature rat cortical slices while large-scale activity was imaged optically with fura-2 AM. Here I show that activation of muscarinic acetylcholine receptors results in waves of correlated neural activity. Waves recruit large numbers of neurons, are slowly propagating, regenerative events involving depolarization and associated calcium transients, and advance for many millimeters as a sharp wave front perpendicular to the pial surface, at speeds ranging between 50 and 300 m/sec. The expression of waves is restricted temporally to a brief period in postnatal development, until postnatal day 6, and spatially to some neocortical areas. The ability of isolated neocortical networks to generate large-scale patterned activity endogenously during a period of massive neurite extension and synaptogenesis raises the possibility that at least in some cortical areas these processes might be influenced by patterned neuronal firing generated independently of thalamocortical input.}, Author = {Peinado, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-08-27 03:09:30 +0000}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Fluorescence;10 Development;Receptors, Glutamate;Rats, Long-Evans;Animals;In Vitro;Rats;10 Structural plasticity;Muscarinic Agonists;Receptors, Muscarinic;Neocortex;Patch-Clamp Techniques;Beta;Calcium;Animals, Newborn;10 Spiny stellate;Action Potentials;Muscarine;Neurons;Nerve Net;Support, U.S. Gov't, P.H.S.;Carbachol; currOpinRvw}, Medline = {20276372}, Month = {1}, Nlm_Id = {8102140}, Number = {2}, Organization = {Department of Neuroscience, Albert Einstein College of Medicine, Bronx,New York 10461, USA. peinado\@aecom.yu.edu}, Pages = {RC54}, Pubmed = {10632620}, Title = {Traveling slow waves of neural activity: a novel form of network activity in developing neocortex}, Uuid = {75C52A06-9508-4D96-B036-73EF1B0536C0}, Volume = {20}, Year = {2000}, url = {papers/Peinado_JNeurosci2000.pdf}} @article{Peinado:1993a, Abstract = {A low molecular weight intracellular tracer, Neurobiotin, was injected into single neurons in living slices of rat neocortex made at postnatal days 5-18. Between days 5 and 12, 66\%of single-neuron injections labeled clusters of up to 80 neurons surrounding the injected cell. Coupling between neurons occurred primarily through dendrites. Injections done in the presence of halothane, a gap junction blocker, abolished the spread of tracer to surrounding neurons, implying that gap junctions mediate coupling. Injections done after day 16 resulted in little or no dye coupling. We conclude that transient local coupling via gap junctions in developing cortex may provide a pathway for communicating intercellular signals, including subthreshold electrical activity, and thereby enable temporal coordination of local neuronal ensembles during circuit formation.}, Author = {Peinado, A. and Yuste, R. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Animals;Electric Conductivity;Aging;Rats;10 Structural plasticity;Beta;Intercellular Junctions;Pyramidal Tracts;Dendrites;Support, Non-U.S. Gov't;10 Spiny stellate;Cerebral Cortex;21 Neurophysiology;Halothane;Neurons;Support, U.S. Gov't, P.H.S.;Biotin}, Medline = {93152166}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710.}, Pages = {103-14}, Pubmed = {8427699}, Title = {Extensive dye coupling between rat neocortical neurons during the period of circuit formation}, Uuid = {776AF624-4888-43EA-BC4C-3AABB691C71C}, Volume = {10}, Year = {1993}} @article{Pekcec:2006, Abstract = {Multipotent neural precursors have been suggested to exist in many parts of the adult mammalian brain. In the present study, we characterized the neurogenic potential in the piriform cortex of adult rats. Proliferation rates as detected by 5'-bromodeoxyuridine-labeling proved to be low when compared with the major neurogenic brain regions (i.e. the hippocampus and the subventricular zone). 5'-Bromodeoxyuridine/NeuN-labeling in accordance with doublecortin, polysialylated neural cell adhesion molecule, and TUC-4-labeling indicated that neuronal differentiation of newborn cells occurs predominantly in layer II of the piriform cortex. Many of the cells exhibited a pyramidal cell morphology. The lack of 5'-bromodeoxyuridine/NeuN-labeled cells 12 weeks after 5'-bromodeoxyuridine administration argued against long-term survival of newborn neurons in the piriform cortex.}, Author = {Pekcec, Anton and L{\"o}scher, Wolfgang and Potschka, Heidrun}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9100935}, Number = {6}, Organization = {aDepartment of Pharmacology, Toxicology, and Pharmacy, University of Veterinary Medicine and bCenter for Systems Neuroscience, Hannover, Germany.}, Pages = {571-4}, Pii = {00001756-200604240-00003}, Pubmed = {16603913}, Title = {Neurogenesis in the adult rat piriform cortex}, Uuid = {6FA19224-E333-4D7F-933E-776EA1F7C2BE}, Volume = {17}, Year = {2006}} @article{Pellegrini:1996, Abstract = {Emx 1 and 2 are the murine homologues of the Drosophila empty spiracles gene and based on their expression pattern may be involved in the regional specification of the mammalian forebrain. During early embryogenesis, Emx2 is expressed in the presumptive cerebral cortex and olfactory bulbs and later, in the hippocampus proper and dentate gyrus. The latter are involved in memory processes. To understand the role of Emx2 in vivo, we have mutated the gene in mice. Homozygous embryos die postnatally because of severe urogenital alterations. These mice present cerebral hemispheres with a reduced size and exhibit specific morphological alterations in allocortical structures of the medial wall of the brain. The dentate gyrus is missing and the hippocampus proper is reduced. The medial limbic cortex is also severely shortened. The development of the dentate gyrus is affected at the onset of its formation with defects in the neuroepithelium from which it originates. These findings demonstrate that Emx2 is required for the development of several forebrain structures.}, Author = {Pellegrini, M. and Mansouri, A. and Simeone, A. and Boncinelli, E. and Gruss, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Research Support, Non-U.S. Gov't;Genes, Lethal;Limbic System;Nerve Tissue Proteins;Dentate Gyrus;Hippocampus;Mice, Mutant Strains;Urogenital Abnormalities;Mice;Brain;Homeodomain Proteins;Urogenital System;Animals}, Medline = {97164702}, Month = {12}, Nlm_Id = {8701744}, Number = {12}, Organization = {Max-Planck-Institute of Biophysical Chemistry, G{\"o}ttingen.}, Pages = {3893-8}, Pubmed = {9012509}, Title = {Dentate gyrus formation requires Emx2}, Uuid = {AD8B2118-A3E5-11DA-AB00-000D9346EC2A}, Volume = {122}, Year = {1996}, url = {papers/Pellegrini_Development1996.pdf}} @article{Pelletier:1996, Abstract = {1. Focal cortical epilepsy was investigated by applying tetanic stimulation repeatedly (100 Hz. 2 s in duration, once every 10 min, 10 episodes) to layer III association fibers in rat piriform cortex slices and recording both extracellular and intracellular responses from the endopiriform nucleus. To promote excitability, piriform slices were incubated in artificial cerebrospinal fluid (ACSF) containing 0.9 mM Mg2+ and 5 mM K+, at an initial temperature of 10-12 degrees C, which was allowed to warm passively to room temperature. 2. Responses recorded extracellularly in the endopiriform nucleus consisted of two types: weak stimulation evoked an early-occurring, small-amplitude, negatively deflecting potential; strong stimulation evoked a more complex response comprising both an early potential of maximal amplitude and a later-occurring epileptiform potential of greater amplitude and longer duration. Late-occurring epileptiform potentials were not observed in slices incubated in ACSF at room temperature. 3. Both the early potential and the late-occurring epileptiform responses were abolished by the non-N-methyl-D-aspartic acid (non-NMDA) subtype of glutamate receptor blocker, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 10 microM). Application of D(-)-2-amino-5-phosphonopentanoic acid (APV; 50 microM) to block NMDA receptors was without effect on the early potential but diminished the late-occurring epileptiform potential. The late-occurring potential was unable to follow stimulation delivered at a frequency of 1 Hz. These results suggest that the early potential was generated monosynaptically and dependent solely on the activation of non-NMDA receptors, whereas the late-occurring epileptiform potential was polysynaptic in origin and possessed both a CNQX- and an APV-sensitive component. 4. Responses increased progressively in both amplitude and duration after tetanic stimulation. The threshold intensity required to evoke the complex dual-component potential was reduced by tetanic stimulation. An increase in multiunit spiking activity, indicating an increase in synchronous discharges, was also observed. A residual potential could be evoked in the presence of CNQX (10 microM) after the tetanic stimulation procedure. 5. Spontaneous discharges occurred as early as after the first episode of tetanic stimulation and persisted for the duration of the experiment. Spontaneous discharges were abolished by either CNQX or by a fourfold increase in extracellular Mg2+ concentration, the latter reversibly. APV reduced the frequency of spontaneous discharges by 38.6 +/- 9.3\%(mean +/- SE). The conventional anticonvulsant drug 5,5-diphenylhydantoin, the benzodiazepine receptor agonist midazolam, and the benzodiazepine receptor antagonist flumazenil were without effect on the frequency of spontaneous discharges. Evoked responses were also unaffected by either 5,5-diphenylhydantoin or midazolam. Slices not exposed to cold ACSF, although demonstrating potentiation of evoked responses after tetanization did not produce spontaneous epileptiform discharges. 6. Intracellular recordings from endopiriform neurons revealed the cellular correlates of the extracellular responses. Weak stimulation evoked a small-amplitude depolarizing potential. Increasing the intensity of stimulation increased the amplitude of this response and also evoked a second depolarizing potential of greater amplitude occurring at variable latencies. Maximal stimulation evoked an action potential. After tetanic stimuli, responses resembling a paroxysmal depolarizing shift consisting of a depolarizing potential with superimposed multiple action potentials were evoked reliably. Passive membrane properties after repeated tetanic stimulation were not different when compared with control. 7. This novel model of in vitro focal cortical epilepsy has many features characteristic of conventional kindling including 1) progressive nature; 2) reduced threshold to evoke discharges; and 3) persist}, Author = {Pelletier, M. R. and Carlen, P. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Excitatory Amino Acid Antagonists;Research Support, Non-U.S. Gov't;Electric Stimulation;Epilepsies, Partial;In Vitro;Evoked Potentials;Rats;Animals;21 Epilepsy;Rats, Wistar;Disease Models, Animal;Male;Action Potentials;Olfactory Pathways;Tetany;21 Neurophysiology;Neurons;Membrane Potentials;Excitatory Amino Acids;24 Pubmed search results 2008;Anticonvulsants}, Medline = {97138917}, Month = {12}, Nlm_Id = {0375404}, Number = {6}, Organization = {Playfair Neuroscience Unit, Toronto Hospital Research Institute, Department of Medicine (Neurology), University of Toronto, Ontario, Canada.}, Pages = {4069-79}, Pubmed = {8985901}, Title = {Repeated tetanic stimulation in piriform cortex in vitro: epileptogenesis and pharmacology}, Uuid = {73A01A3C-2BE2-4FDA-9095-08CF5A68D2B9}, Volume = {76}, Year = {1996}} @article{Pellier:1994, Abstract = {Immunocytochemical and histochemical methods have been used to describe the neuronal population migrating from the rat olfactory placode and to analyze the spatio-temporal evolution of this neuronal migration during development. Several neuronal markers, such as binding to the lectin Ulex europaeus (UEA I) and the presence of neuron-specific enolase (NSE), olfactory marker protein (OMP), and luteinizing hormone-releasing hormone (LHRH), have been tested in order to determine whether migrating neurons originate from both the medial and the lateral parts of the placode and whether they all express LHRH. Our data show that a large population of differentiated migrating neurons can be identified with an antibody against NSE from the 14th day of gestation and with UEA I one day later. Migrating neurons are closely associated with both the vomeronasal axon fascicles emerging from the medial pit and the olfactory axons originating from the lateral pit. However, the neuron migration from the lateral pit appears to be more discrete than that from the medial pit. No LHRH immunoreactivity has been detected among neurons migrating from the lateral pit. Some neurons accompanying the olfactory axon fascicles exhibit a high level of maturation as shown by their OMP-positivity. Numerous neurons positive for both NSE and UEA I have also been observed within the presumptive olfactory nerve layer in early embryonic stages. eng Journal Article}, Author = {Pellier, V. and Astic, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Journal = {Cell Tissue Res}, Keywords = {I abstr;Pregnancy;13 Olfactory bulb anatomy;Neurons/chemistry/*physiology;Rats;Glycoconjugates/analysis;Immunoenzyme Techniques;Female;Cell Movement;Animal;Nasal Cavity/chemistry/cytology/*innervation;Antibodies;Epithelium/chemistry/cytology;Support, Non-U.S. Gov't;Animals, Newborn;Rats, Wistar/embryology;Phosphopyruvate Hydratase/analysis;Gonadorelin/analysis;Lectins;Olfactory Bulb/*chemistry/cytology;Fetal Development}, Number = {3}, Organization = {Laboratoire de Physiologie Neurosensorielle, UCB/Lyon I, Villeurbanne, France.}, Pages = {587-98.}, Title = {Histochemical and immunocytochemical study of the migration of neurons from the rat olfactory placode}, Uuid = {325FF868-8385-409F-9CE5-B760B6446427}, Volume = {275}, Year = {1994}} @article{Peluffo:2003, Abstract = {Successful introduction of therapeutic genes into the central nervous system (CNS) requires the further development of efficient transfer vehicles that avoid viral vector-dependent adverse reactions while maintaining high transfection efficiency. The multifunctional protein 249AL was recently constructed for in vitro gene delivery. Here, we explore the capability of this vector for in vivo gene delivery to the postnatal rat CNS. Significant transgene expression was observed both in the excitotoxically injured and noninjured brain after intracortical injection of the DNA-contaning-249AL vector. In the injured brain, a widespread expression occurred in the entire lesioned area and retrograde transport of the vector toward distant thalamic nuclei and transgene expression were observed. Neurons, astrocytes, microglia, and endothelial cells expressed the transgene. No recruitment of leukocytes, demyelination, interleukin-1beta expression, or increase in astrocyte/microglial activation was observed at 6 days postinjection. In conclusion, the 249AL vector shows promising properties for gene therapy intervention in the CNS, including the targeting of different cell populations.}, Author = {Peluffo, H. and Ar{\'\i}s, A. and Acarin, L. and Gonz{\'a}lez, B. and Villaverde, A. and Castellano, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1043-0342}, Journal = {Hum Gene Ther}, Keywords = {Research Support, Non-U.S. Gov't;beta-Galactosidase;Animals;Densitometry;Rats;Transfection;Comparative Study;11 Glia;Green Fluorescent Proteins;Genetic Vectors;Gene Therapy;Blotting, Western;Escherichia coli;Luminescent Proteins;Central Nervous System;Immunohistochemistry;Gene Expression;Transgenes}, Medline = {22833556}, Month = {9}, Nlm_Id = {9008950}, Number = {13}, Organization = {Unitat d'Histologia, Departament de Biologia Cellular, Fisiologia i Immunologia, Universitat Aut\`{o}noma de Barcelona, 08193 Barcelona, Spain. hugo.peluffo\@uab.es}, Pages = {1215-23}, Pubmed = {12952593}, Title = {Nonviral gene delivery to the central nervous system based on a novel integrin-targeting multifunctional protein}, Uuid = {A2B02FE1-F129-4C40-AEAA-7049B089ED6D}, Volume = {14}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/104303403767740759}} @article{Pencea:2001, Abstract = {Throughout life, the anterior part of the postnatal rodent subventricular zone (SVZa), surrounding the lateral ventricles, contains a prolific source of neuronal progenitor cells that retain their capacity to concurrently generate neurons and migrate along the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into interneurons. This study was designed to determine whether the SVZ and RMS of the postnatal primate also harbor a specialized population of neuronal progenitors with the capacity to divide while they migrate. In order to reveal the spatial-temporal changes in the distribution and composition of the neuronal progenitor cells in the primate SVZ and RMS, seven rhesus monkeys, ranging in age from 2 days to 8 years, were given a single injection of the cell proliferation marker bromodeoxyuridine (BrdU) 3 h before they were perfused. The phenotypic identity of the BrdU(+) cells was revealed by double labeling sagittal sections with cell type-specific markers. From birth onward the distribution of BrdU(+) cells with a neuronal phenotype is extensive and largely overlapping with that of the rodent. Similar to the rodent brain the neuronal progenitors are most numerous in neonates. The BrdU(+) neurons in the primate forebrain extend lateral and ventral to the lateral ventricle and all along the RMS. The cytoarchitectonic arrangement and appearance of the neuronal progenitor cells is quite varied in the primate compared to the rodent; in some locations the cells are aligned in parallel arrays resembling the neuronal chains of the adult rodent RMS, whereas in other positions the cells have a homogeneous "honeycomb"arrangement. The chains are progressively more pervasive in older primates. Akin to the RMS of adult rodents, in the primate SVZ and RMS the astrocytes often form long tubes enveloping the chains of neuronal progenitors. Our study demonstrates that the primate forebrain, similar to the rodent forebrain, harbors a specialized population of mitotically active neuronal progenitor cells that undergo extensive rearrangements while continuing to proliferate throughout life. Copyright 2001 Academic Press.}, Author = {Pencea, V. and Bingaman, K. D. and Freedman, L. J. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Rodentia;Cell Differentiation;Animals;Aging;Rats;Comparative Study;Phenotype;Cell Count;02 Adult neurogenesis migration;Cell Movement;Olfactory Bulb;Prosencephalon;Macaca mulatta;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;B;Neurons;Cell Division;24 Pubmed search results 2008;Immunohistochemistry;Stem Cells;Bromodeoxyuridine;Lateral Ventricles;Research Support, Non-U.S. Gov't}, Medline = {21538599}, Month = {11}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322}, Pages = {1-16.}, Pii = {S0014488601977684}, Pubmed = {11681836}, Title = {Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain}, Uuid = {366B65DE-0FFE-4530-AA64-93D9181BD7E4}, Volume = {172}, Year = {2001}, url = {papers/Pencea_ExpNeurol2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.2001.7768}} @article{Pencea:2003, Abstract = {The aim of this study was to elucidate the embryological origins of the unique neuronal progenitor cells that form the rostral migratory stream (RMS), the path traversed by cells from the anterior part of the forebrain subventricular zone (SVZa) en route to the olfactory bulb. To determine when and where cells constituting the RMS initially exhibit their characteristic neuronal phenotype and high mitotic capacity, we analyzed the cells of the rat forebrain between embryonic day 14 (E14) and postnatal day 2 (P2). At E14, cells with a neuronal phenotype were observed within the ventricular zone in close proximity to the mantle layer of the future olfactory bulb. By E15, cells expressing neuronal markers are also PSA-NCAM immunoreactive and become aligned in chains of similarly oriented cells, a hallmark of the postnatal RMS. The cells that form chains organize into a patch that enlarges in the anterior-posterior and medial-lateral dimensions from E16 to E22 (birth). In comparing the forebrain cytoarchitecture to the pattern of cell type-specific staining, the patch constitutes only the central part of the proximal RMS. Early during development, the region of the RMS surrounding the patch expresses low levels of PSA-NCAM and neuron-specific markers. The proliferative activity of cells forming the patch vs. nonpatch regions of the RMS was analyzed following a short bromodeoxyuridine (BrdU) exposure. Between E15 and E22, the patch can be recognized by the mitotic activity of its cells; the cells of the patch incorporate less BrdU than the nonpatch portion of the RMS. The time course of appearance of cells forming the RMS indicates that the RMS arises in advance and independently of the cortical SVZ. Although the patch and the nonpatch regions of the embryonic RMS appear to merge postnatally, the two regions may originate separately under the influence of distinct intrinsic and extrinsic factors.}, Author = {Pencea, Viorica and Luskin, Marla B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Cell Movement;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Immunohistochemistry;Rats;Research Support, U.S. Gov't, P.H.S.;Neural Cell Adhesion Molecule L1;Cell Division;Stem Cells;Animals, Newborn;Olfactory Bulb;Prosencephalon;Cerebral Ventricles;Bromodeoxyuridine;Sialic Acids;Neurons;Animals}, Medline = {22719500}, Month = {9}, Nlm_Id = {0406041}, Number = {4}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.}, Pages = {402-18}, Pubmed = {12836176}, Title = {Prenatal development of the rodent rostral migratory stream}, Uuid = {C388116B-2C66-435E-B422-6C2311CB4C8D}, Volume = {463}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10746}} @article{Pencea:2001a, Abstract = {The findings that brain-derived neurotrophic factor (BDNF) promotes in vitro the survival and/or differentiation of postnatal subventricular zone (SVZ) progenitor cells and increases in vivo the number of the newly generated neurons in the adult rostral migratory stream and olfactory bulb prompted us to investigate whether the infusion of BDNF influences the proliferation and/or differentiation of cells in other regions of the adult forebrain. We examined the distribution and phenotype of newly generated cells in the adult rat forebrain 16 d after intraventricular administration of BDNF in conjunction with the cell proliferation marker bromodeoxyuridine (BrdU) for 12 d. BDNF infusion resulted in numerous BrdU(+) cells, not only in the SVZ lining the infused lateral ventricle, but moreover, in specific parenchymal structures lining the lateral and third ventricles, including the striatum and septum, as well as the thalamus and hypothalamus, in which neurogenesis had never been demonstrated previously during adulthood. In each region, newly generated cells expressed the neuronal marker microtubule-associated protein-2, or neuron-specific tubulin, identified by the antibody TuJ1. The percentage of the newly generated cells expressing TuJ1 ranged from 27 to 42\%, suggesting that the adult forebrain has a more profound capacity to produce neurons than recognized previously. The extent of cell proliferation after BDNF infusion was correlated with the level of expression of full-length TrkB, the high-affinity receptor for BDNF, despite the fact that the BrdU(+) cells were not themselves TrkB(+). Collectively, our results demonstrate that the adult brain parenchyma may recruit and/or generate new neurons, which could replace those lost as a result of injury or disease.}, Author = {Pencea, V. and Bingaman, K. D. and Wiegand, S. J. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Microtubule-Associated Proteins;Tissue Distribution;Animals;Corpus Striatum;Rats;C both;Phenotype;Brain-Derived Neurotrophic Factor;Antigens, Differentiation;Septum of Brain;Cell Count;Rats, Sprague-Dawley;Injections, Intraventricular;Prosencephalon;Research Support, U.S. Gov't, P.H.S.;Hypothalamus;Thalamus;Neurons;Receptor, trkB;04 Adult neurogenesis factors;Cell Division;24 Pubmed search results 2008;Bromodeoxyuridine;Lateral Ventricles;Research Support, Non-U.S. Gov't}, Medline = {21408167}, Month = {9}, Nlm_Id = {8102140}, Number = {17}, Organization = {Departments of Cell Biology and Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322, and Regeneron Pharmaceuticals Inc., Tarrytown, New York 10591.}, Pages = {6706-17.}, Pii = {21/17/6706}, Pubmed = {11517260}, Title = {Infusion of Brain-Derived Neurotrophic Factor into the Lateral Ventricle of the Adult Rat Leads to New Neurons in the Parenchyma of the Striatum, Septum, Thalamus, and Hypothalamus}, Uuid = {9F1B91C2-BC72-47EB-9CB1-34D00B4551EF}, Volume = {21}, Year = {2001}, url = {papers/Pencea_JNeurosci2001}} @article{Pennartz:2004, Abstract = {The progeny of neural stem cells in the subventricular zone (SVZ) of the adult mammalian brain consists in polysialylated NCAM-expressing immature neurons (PSA(+) cells), which migrate to the olfactory bulb (OB) to differentiate into GABAergic interneurons. We purified murine PSA(+) cells directly from the adult brain by FACS and analyzed their gene expression profile by SAGE. Comparative analyses led to the identification of precursor-enriched genes, including Survivin, Sox-4, Meis2, Dishevelled-2, C3aR1 and Riken 3110003A17, and many so far uncharacterized transcripts. Cluster analysis showed that groups of genes involved in axon guidance and gene clusters implicated in chemotaxis are strongly upregulated, indicating a role of both cues in the control of cell migration in the adult brain. Furthermore, genes involved in apoptosis and cell proliferation are co-expressed, suggesting that the amount of precursors that is present in the adult brain is a result of an equilibrium of these processes.}, Author = {Pennartz, Sandra and Belvindrah, Richard and Tomiuk, Stefan and Zimmer, C{\'e}line and Hofmann, Kay and Conradt, Marcus and Bosio, Andreas and Cremer, Harold}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Cell Differentiation;Cell Culture Techniques;Animals;Cells, Cultured;Gene Expression Regulation, Developmental;Cell Separation;Oligonucleotide Array Sequence Analysis;Brain;Apoptosis;Chemotaxis;Cell Movement;Homeostasis;Mice, Inbred C57BL;Gene Expression Profiling;Male;Sialic Acids;Neurons;Multigene Family;Flow Cytometry;Mice;Cell Division;24 Pubmed search results 2008;Neural Cell Adhesion Molecule L1;Stem Cells;Cues;Interneurons;Nerve Tissue Proteins}, Month = {4}, Nlm_Id = {9100095}, Number = {4}, Organization = {Memorec Biotec GmbH, a Miltenyi Biotec Company, 50829 Cologne, Germany.}, Pages = {692-706}, Pii = {S1044743103003993}, Pubmed = {15080897}, Title = {Purification of neuronal precursors from the adult mouse brain: comprehensive gene expression analysis provides new insights into the control of cell migration, differentiation, and homeostasis}, Uuid = {DA575BEE-B4B0-4D2D-A979-EE67EFD267D6}, Volume = {25}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2003.12.011}} @article{Pennell:1997, Abstract = {In order to illuminate functional roles of microglial cells within neural allografts, we have transplanted both whole and microglial and endothelial cell-depleted E14 neural cell suspensions into the intact striatum of Sprague-Dawley rats. Following posttransplantation times of up to 30 days, the intrastrial allografts were analyzed histochemically using the Griffonia simplicifolia B4 isolectin, a marker for both microglia and blood vessels. Our results indicate that both whole and depleted suspension grafts develop identically in terms of neovascularization and microglial colonization. In both types of transplants microglial cells appeared before any blood vessels were apparent. The main phase of graft vascularization occurred between days 7 and 10 posttransplantation and neovascularization was complete by day 21, as revealed by quantitative image analysis. Microglial cells, which were present as ameboid cells during early posttransplantation times, underwent continuing cell differentiation with time that paralleled graft vascular development. By 30 days posttransplantation microglia within the grafts had assumed the fully ramified phenotype characteristic of resting adult microglia. During graft development and vascularization, microglia were often seen in close proximity to ingrowing blood vessels and vascular sprouts. In conclusion, our study has shown that microglial colonization of grafts and graft vascularization occurs independent of donor-derived microglial and endothelial cells, and suggests that the great majority of microglia and vessels within the graft are host derived. We hypothesize that the host microglia invading the allografts play an active role in promoting graft neovascularization.}, Author = {Pennell, N. A. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0963-6897}, Journal = {Cell Transplant}, Keywords = {Pregnancy;Endothelium;Animals;Cell Separation;Corpus Striatum;Brain Tissue Transplantation;Rats;Microglia;Female;Rats, Sprague-Dawley;Not relevant;11 Glia;Neovascularization, Physiologic;Spinal Cord;Male;Fetal Tissue Transplantation;Support, Non-U.S. Gov't;Cerebral Cortex;Support, U.S. Gov't, Non-P.H.S.;Graft Survival;Brain Stem}, Medline = {97314981}, Nlm_Id = {9208854}, Number = {3}, Organization = {Department of Neuroscience, University of Florida Brain Institute, Gainesville 32610, USA.}, Pages = {221-30}, Pii = {S0963689797000304}, Pubmed = {9171155}, Title = {Colonization of neural allografts by host microglial cells: relationship to graft neovascularization}, Uuid = {ED6E9EE5-71A2-4761-BD48-07204E1F4E35}, Volume = {6}, Year = {1997}} @article{Pennell:1998, Abstract = {In light of a recent interest in the transplantation of cultured microglial cells, we have examined the use of the fluorescent dye Fluoro-Gold (FG) as a tracer for these cells. Following injection into the adult rat brain, FG prelabeled microglial cells were readily traceable for up to 2 weeks with minimal labeling of endogenous cell populations. Some of the injected cells differentiated into ramified microglial cells as a result of exposure to the adult CNS environment. Injection of free FG into the adult rat brain resulted in the widespread labeling of neurons and perivascular cells, but not endogenous microglial cells, indicating that perivascular cells, but not resting microglia, are actively pinocytotic cells of the CNS. Our results show that FG is an effective label for the tracing of transplanted microglial cells.}, Author = {Pennell, N. A. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Neurons;Brain Tissue Transplantation;Cell Differentiation;Rats;Not relevant;Time Factors;Fluorescent Dyes;11 Glia;Microglia;Animals, Newborn;Rats, Wistar;Cells, Cultured;Stilbamidines;Animals;Brain;Cell Movement}, Medline = {98220656}, Month = {5}, Nlm_Id = {8806785}, Number = {1}, Organization = {Department of Neuroscience, University of Florida Brain Institute, Gainesville 32610, USA.}, Pages = {84-8}, Pii = {10.1002/(SICI)1098-1136(199805)23:1<84::AID-GLIA8>3.0.CO;2-4}, Pubmed = {9562187}, Title = {Tracing of fluoro-gold prelabeled microglia injected into the adult rat brain}, Uuid = {BA8B047B-10F8-4EB3-B940-E9A82890FF75}, Volume = {23}, Year = {1998}, url = {papers/Pennell_Glia1998.pdf}} @article{Pennell:1994, Abstract = {The B4-isolectin from Griffonia simplicifolia is known to stain microglial cells in a variety of species. The present report describes a lectin staining method that has been modified to facilitate staining of resting microglia, as well as perivascular cells, in vibratome sections of normal sheep brain. This modified method employs tissue fixed in formaldehyde or paraformaldehyde and requires incubating sections with Triton X-100 prior to staining.}, Author = {Pennell, N. A. and Hurley, S. D. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0301-5564}, Journal = {Histochemistry}, Keywords = {Staining and Labeling;Microtomy;Neuroglia;Lectins;Not relevant;11 Glia;Sheep;Fixatives;Animals}, Medline = {95213184}, Month = {12}, Nlm_Id = {0411300}, Number = {6}, Organization = {Department of Neuroscience, JHMHC, University of Florida, Gainesville 32610.}, Pages = {483-6}, Pubmed = {7535300}, Title = {Lectin staining of sheep microglia}, Uuid = {21648FD2-7CC1-43F6-9012-07514FF8744C}, Volume = {102}, Year = {1994}} @article{Pennisi:2006, Author = {Pennisi, Elizabeth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Signal Transduction;Synaptic Membranes;Animals;Humans;Invertebrates;Multiprotein Complexes;Synaptic Transmission;Brain;news;Evolution, Molecular;Gene Expression Profiling;19 Neocortical evolution;Evolution;Brain Chemistry;Cognition;Receptors, Neurotransmitter;Organ Size;24 Pubmed search results 2008;Membrane Proteins;Nerve Tissue Proteins;Vertebrates}, Month = {10}, Nlm_Id = {0404511}, Number = {5797}, Pages = {244-5}, Pii = {314/5797/244}, Pubmed = {17038601}, Title = {Neuroscience. Brain evolution on the far side}, Uuid = {DE5CB4C2-49D5-478F-99A0-408916094F4B}, Volume = {314}, Year = {2006}, url = {papers/Pennisi_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.314.5797.244}} @article{Pentney:2002, Abstract = {Neuronal migration disorders (NMDs) can be associated with neurological dysfunction such as mental retardation, and clusters of disorganized cells (heterotopias) often act as seizure foci in medically intractable partial epilepsies. Methylazoxymethanol (MAM) treatment of pregnant rats results in neuronal heterotopias in offspring, especially in hippocampal area CA1. Although the neurons in dysplastic areas in this model are frequently hyperexcitable, the precise mechanisms controlling excitability remain unclear. Here, we used IR-DIC videomicroscopy and whole cell voltage-clamp techniques to test whether the potent anti-excitatory actions of neuropeptide Y (NPY) affected synaptic excitation of heterotopic neurons. We also compared several synaptic and intrinsic properties of heterotopic, layer 2-3 cortical, and CA1 pyramidal neurons, to further characterize heterotopic cells. NPY powerfully inhibited synaptic excitation onto normal and normotopic CA1 cells but was nearly ineffective on responses evoked in heterotopic cells from stimulation sites within the heterotopia. Glutamatergic synaptic responses on heterotopic cells exhibited a comparatively small, D-2-amino-5-phosphopentanoic acid-sensitive, N-methyl-D-aspartate component. Heterotopic neurons also differed from normal CA1 cells in postsynaptic membrane currents, possessing a prominent inwardly rectifying K(+) current sensitive to Cs(+) and Ba(2+), similar to neocortical layer 2-3 pyramidal cells. CA1 cells instead had a prominent Cs(+)- and 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino) pyrimidinium chloride-sensitive I(h) and negligible inward rectification, unlike heterotopic cells. Thus heterotopic CA1 cells appear to share numerous physiological similarities with neocortical neurons. The lack of NPY's effects on intra-heterotopic inputs, the small contribution of I(h), and abnormal glutamate receptor function, may all contribute to the lowered threshold for epileptiform activity observed in hippocampal heterotopias and could be important factors in epilepsies associated with NMDs.}, Author = {Pentney, A. R. and Baraban, S. C. and Colmers, W. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Research Support, Non-U.S. Gov't;Pregnancy;Synaptic Membranes;Electrophysiology;Animals;Rats;21 Epilepsy;Neocortex;Female;Epilepsy;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Abnormalities, Drug-Induced;Teratogens;Neuropeptide Y;Research Support, U.S. Gov't, P.H.S.;Histocytochemistry;Potassium Channels;21 Neurophysiology;Methylazoxymethanol Acetate;Potassium Channel Blockers;Membrane Potentials;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Medline = {22311398}, Month = {11}, Nlm_Id = {0375404}, Number = {5}, Organization = {Department of Pharmacology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.}, Pages = {2745-54}, Pubmed = {12424309}, Title = {NPY sensitivity and postsynaptic properties of heterotopic neurons in the MAM model of malformation-associated epilepsy}, Uuid = {4C5247FA-16D3-406C-A6E8-E07E44060733}, Volume = {88}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00500.2002}} @article{Pena:2007, Abstract = {The use of arynes and related species as substrates in metal-catalyzed cycloaddition reactions leads to structurally interesting products. Palladium-catalyzed cyclotrimerization of arynes provides a new method for the synthesis of polycyclic aromatic hydrocarbons. For instance, the chemoselective formal [2 + 2 + 2] cocycloaddition of 2,3-triphenylynes with alkynes affords extended triphenylenes, which are good candidates to behave as liquid crystals. Cotrimerization of benzyne and electron-deficient alkenes selectively affords dihydrophenanthrenes or ortho-olefinated biaryls depending on the catalytic system employed. The use of 2,2'-bis(diphenylphosphino)-1,1'-binophythyl (BINAP)-based palladium(0) catalysts in the cocyclotrimerization of 7-methoxynaphthalyne and dimethyl acetylenedicarboxylate affords an enantiomerically enriched tetrasubstituted pentahelicene, the first example of a metal-catalyzed enantioselective reaction involving arynes. Strained cyclic alkynes can also participate in the palladium-catalyzed cyclotrimerization reactions, which again lead to structurally interesting products. (c) 2007 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 7: 326-333; 2007: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20132.}, Author = {Pe\~{n}a, and P{\'e}rez, and Guiti{\'a}n,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1527-8999}, Journal = {Chem Rec}, Keywords = {24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {101085550}, Number = {6}, Organization = {Departamento de Qu{\'\i}mica Org{\'a}nica, Facultad de Qu{\'\i}mica, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain.}, Pages = {326-333}, Pubmed = {18050279}, Title = {Cyclotrimerization reactions of arynes and strained cycloalkynes}, Uuid = {B61C3A8A-4CDF-4215-BA20-32A7D48779AF}, Volume = {7}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/tcr.20132}} @article{Peretto:1999, Abstract = {The persistence of neurogenesis and structural plasticity was believed until recently to be restricted to lower vertebrates and songbirds. Nevertheless, it has now been ascertained that these phenomena can occur in the adult mammalian nervous system, at least in three distinct sites: the olfactory neuroepithelium of the nasal mucosa and two brain regions, namely, the hippocampal dentate gyrus and the olfactory bulb. The newly generated cells of the olfactory bulb originate from the subependymal layer, a remnant of the primitive subventricular zone persisting in the adult forebrain. Besides being characterized by high rates of cell proliferation, the subependymal layer is a site of long- distance tangential cell migration, wherein migrating cells form chains enwrapped by a particular type of astrocytes. These glial cells give rise to channels (glial tubes) that separate single chains from the surrounding mature tissue. The cellular composition and the pattern of cell migration in the mammalian subependymal layer appear to be quite different in neonatal and adult animals, changing strikingly in the postnatal period. Other features of uniqueness involve the capability of neuronal precursors to divide while undergoing migration and the presence of multipotent stem cells. Thus, the subependymal layer is an area of the adult mammalian brain endowed with a cohort of phenomena proper of neural development, persisting into (and adapted to) the fully mature nervous tissue. Such features make this system an optimal model to unravel mechanisms permitting highly dynamic structural plasticity during adulthood, in the perspective of providing strategies for possible brain repair.}, Author = {Peretto, P. and Merighi, A. and Fasolo, A. and Bonfanti, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Brain Res Bull}, Keywords = {*Cell Movement;Cell Adhesion Molecules/analysis;Cell Differentiation;02 Adult neurogenesis migration;B;Prosencephalon/chemistry/*cytology;Neurons/chemistry/cytology/*physiology;Rats;*Neuronal Plasticity;Immunohistochemistry;Cell Division;Animal;Support, Non-U.S. Gov't;Mice;Neuroglia/chemistry/*cytology}, Number = {4}, Organization = {Department of Veterinary Morphophysiology, University of Turin, Italy.}, Pages = {221-43.}, Title = {The subependymal layer in rodents: a site of structural plasticity and cell migration in the adult mammalian brain}, Uuid = {75FAA72B-50D0-4F51-B094-99F755B10F44}, Volume = {49}, Year = {1999}, url = {../../Volumes/Vega/Users/ackman/James/Endnotelibraries/OMEGAData/2449757952perettoreview}} @article{Peri:2008, Abstract = {A significant proportion of neurons in the brain undergo programmed cell death. In order to prevent the diffusion of damaging degradation products, dying neurons are quickly digested by microglia. Despite the importance of microglia in several neuronal pathologies, the mechanism underlying their degradation of neurons remains elusive. Here, we exploit a microglial population in the zebrafish to study this process in intact living brains. In vivo imaging reveals that digestion of neurons occurs in compartments arising from the progressive fusion of vesicles. We demonstrate that this fusion is mediated by the v0-ATPase a1 subunit. By applying live pH indicators, we show that the a1 subunit mediates fusion between phagosomes and lysosomes during phagocytosis, a function that is independent of its proton pump activity. As a real-time description of microglial phagocytosis in vivo, this work advances our understanding of microglial-mediated neuronal degeneration, a hallmark of many neuronal diseases.}, Author = {Peri, Francesca and N{\"u}sslein-Volhard, Christiane}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {Zebrafish;research support, non-u.s. gov't;Embryo, Nonmammalian;Animals, Genetically Modified;Apoptosis;Zebrafish Proteins;Vacuolar Proton-Translocating ATPases;Microglia;Phagosomes;Animals;Brain;Phagocytosis;Neurons;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0413066}, Number = {5}, Organization = {Max Planck Institute for Developmental Biology, Spemannstr. 35, 72076 T{\"u}bingen, Germany. peri\@embl.de}, Pages = {916-27}, Pii = {S0092-8674(08)00611-9}, Pubmed = {18510934}, Title = {Live imaging of neuronal degradation by microglia reveals a role for v0-ATPase a1 in phagosomal fusion in vivo}, Uuid = {A9AB465A-93F2-4948-B200-515C71032D57}, Volume = {133}, Year = {2008}, url = {papers/Peri_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.04.037}} @article{Perron:2005, Abstract = {Antigen expression of a human endogenous retrovirus family, HERV-W, in normal human brain and multiple sclerosis lesions was studied by immunohistochemistry by three independent groups. The HERV-W multicopy family was identified in human DNA from the previously characterized multiple sclerosis-associated retroviral element (MSRV). A panel of antibodies against envelope (ENV) and capsid (GAG) antigens was tested. A physiological expression of GAG proteins in neuronal cells was observed in normal brain, whereas there was a striking accumulation of GAG antigen in axonal structures in demyelinated white matter from patients with MS. Prominent HERV-W GAG expression was also detected in endothelial cells of MS lesions from acute or actively demyelinating cases, a pattern not found in any control. A physiological expression of ENV proteins was detected in microglia in normal brain; however,a specific expression in macrophages was apparently restricted to early MS lesions. Thus, converging results from three groups confirm that GAG and ENV proteins encoded by the HERV-W multicopy gene family are expressed in cells of the central nervous system under normal conditions. Similar to HERV-W7q ENV (Syncitin), which is expressed in placenta and has been shown to have a physiological function in syncytio-trophoblast fusion, HERV-W GAG may thus also have a physiological function in human brain. This expression differs in MS lesions, which may either reflect differential regulation of inherited HERV-W copies, or expression of "infectious" MSRV copies. This is compatible with a pathophysiological role in MS, but also illustrates the ambivalence of such HERV antigens, which can be expressed in cell-specific patterns, under physiological or pathological conditions.}, Author = {Perron, Herv{\'e} and Lazarini, Fran\c{c}oise and Ruprecht, Klemens and P{\'e}choux-Longin, Christine and Seilhean, Danielle and Sazdovitch, V{\'e}ronique and Cr{\'e}ange, Alain and Battail-Poirot, Nicole and Siba{\"\i}, Genevi\`{e}ve and Santoro, Lyse and Jolivet, Michel and Darlix, Jean-Luc L. and Rieckmann, Peter and Arzberger, Thomas and Hauw, Jean-Jacques J. and Lassmann, Hans}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1355-0284}, Journal = {J Neurovirol}, Keywords = {Endogenous Retroviruses;Multiple Sclerosis;Adult;Aged;Immunohistochemistry;Female;Gene Products, env;multicenter study;Middle Aged;Microglia;11 Glia;Humans;Brain;Gene Products, gag;Neurons;Male}, Month = {2}, Nlm_Id = {9508123}, Number = {1}, Organization = {bioM{\'e}rieux, R&D, Chemin de l'Orme, 69280 Marcy L'Etoile, France. herve\_perron\@eu.biomerieux.com}, Pages = {23-33}, Pii = {LXQWW2G05118N6M1}, Pubmed = {15804956}, Title = {Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions}, Uuid = {79EC0B8C-EE5A-11DA-8605-000D9346EC2A}, Volume = {11}, Year = {2005}, url = {papers/Perron_JNeurovirol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/13550280590901741}} @article{Persons:1997, Abstract = {We have investigated the utility of the green fluorescent protein (GFP) to serve as a marker to assess retroviral gene transfer into hematopoietic cells and as a tool to identify and enrich for cells expressing high levels of the vector-encoded transcript. GFP, by virtue of a naturally occurring chromophore encoded in its primary sequence, displays autonomous fluorescence, thus eliminating the need for antibody or cytochemical staining to detect its expression. A bicistronic murine stem cell virus (MSCV)-based retroviral vector was constructed containing the GFP cDNA and a mutant, human dihydrofolate reductase gene. High-titer, ecotropic retroviral producer cells free of replication competent virus were generated and used to transduce murine bone marrow cells by cocultivation. Within 24 hours after completion of the transduction procedure, a high proportion (40\%to 70\%) of the marrow cells were intensely fluorescent compared to mock-transduced cells or cells transduced with a control retrovirus. Erythroid and myeloid hematopoietic colonies derived from GFP-transduced marrow were easily scored for retroviral gene transfer by direct in situ fluorescence microscopy. Clonogenic progenitors expressing increased levels of antifolate drug resistance could be enriched from the GFP-transduced marrow population by fluorescence activated cell sorting of cells expressing high levels of GFP. In vivo, splenic hematopoietic colonies and peripheral blood cells from animals transplanted with GFP-transduced marrow displayed intense fluorescence. These results show that GFP is an excellent marker for scoring and tracking gene-modified hematopoietic cells and for allowing rapid selection and enrichment of transduced cells expressing high levels of the transgene.}, Author = {Persons, D. A. and Allay, J. A. and Allay, E. R. and Smeyne, R. J. and Ashmun, R. A. and Sorrentino, B. P. and Nienhuis, A. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Gene Transfer Techniques;Luminescent Proteins;Research Support, Non-U.S. Gov't;Bone Marrow Cells;Hematopoiesis;Research Support, U.S. Gov't, P.H.S.;Retroviridae;Genetic Markers;Gene Expression;11 Glia;Green Fluorescent Proteins;Animals;Humans;Mice;Genetic Vectors}, Medline = {97436537}, Month = {9}, Nlm_Id = {7603509}, Number = {5}, Organization = {Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.}, Pages = {1777-86}, Pubmed = {9292510}, Title = {Retroviral-mediated transfer of the green fluorescent protein gene into murine hematopoietic cells facilitates scoring and selection of transduced progenitors in vitro and identification of genetically modified cells in vivo}, Uuid = {235CD182-647C-4D86-AF05-382D1D3D14B8}, Volume = {90}, Year = {1997}} @article{Pertz:2006, Abstract = {Rho family GTPases regulate the actin and adhesion dynamics that control cell migration. Current models postulate that Rac promotes membrane protrusion at the leading edge and that RhoA regulates contractility in the cell body. However, there is evidence that RhoA also regulates membrane protrusion. Here we use a fluorescent biosensor, based on a novel design preserving reversible membrane interactions, to visualize the spatiotemporal dynamics of RhoA activity during cell migration. In randomly migrating cells, RhoA activity is concentrated in a sharp band directly at the edge of protrusions. It is observed sporadically in retracting tails, and is low in the cell body. RhoA activity is also associated with peripheral ruffles and pinocytic vesicles, but not with dorsal ruffles induced by platelet-derived growth factor (PDGF). In contrast to randomly migrating cells, PDGF-induced membrane protrusions have low RhoA activity, potentially because PDGF strongly activates Rac, which has previously been shown to antagonize RhoA activity. Our data therefore show that different extracellular cues induce distinct patterns of RhoA signalling during membrane protrusion.}, Author = {Pertz, Olivier and Hodgson, Louis and Klemke, Richard L. and Hahn, Klaus M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {0410462}, Number = {7087}, Organization = {University of North Carolina at Chapel Hill, Department of Pharmacology and Lineberger Cancer Center, Chapel Hill, North Carolina 27599, USA. khahn\@med.unc.edu}, Pages = {1069-72}, Pii = {nature04665}, Pubmed = {16547516}, Title = {Spatiotemporal dynamics of RhoA activity in migrating cells}, Uuid = {2D00F86D-884D-4409-AD7F-D7529089F755}, Volume = {440}, Year = {2006}, url = {papers/Pertz_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04665}} @article{Peterlin:2000, Abstract = {An experimental difficulty in unraveling circuits in the mammalian nervous system is the identification of postsynaptic targets of a given neuron. Besides ultrastructural reconstructions, simultaneous recordings from pairs of cells in brain slices have been used to identify connected neurons. We describe in this paper a technique using calcium imaging that allows rapid identification of potential postsynaptic targets. This method consists of stimulating one neuron ("trigger") while imaging a population of cells to detect which other neurons ("followers") are activated by the trigger. By using bulk-loading of calcium indicators in slices of mouse visual cortex, we demonstrate that neurons that display somatic calcium transients time-locked to the spikes of a trigger neuron can be monosynaptically connected to it. This technique could be applied to reconstruct and assay circuits in the central nervous system.}, Author = {Peterlin, Z. A. and Kozloski, J. and Mao, B. Q. and Tsiola, A. and Yuste, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Visual Cortex;Magnesium;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred C57BL;Fluorescent Dyes;In Vitro;21 Calcium imaging;21 Circuit structure-function;Calcium;Fura-2;Mice;Animals;24 Pubmed search results 2008;Optics;Neurons}, Medline = {20202685}, Month = {3}, Nlm_Id = {7505876}, Number = {7}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {3619-24}, Pii = {97/7/3619}, Pubmed = {10737806}, Title = {Optical probing of neuronal circuits with calcium indicators}, Uuid = {D1F9DF18-1CE1-46FF-8A0F-665E9C168098}, Volume = {97}, Year = {2000}, url = {papers/Peterlin_ProcNatlAcadSciUSA2000.pdf}} @article{Peters:2004, Abstract = {Freeze-lesion induced neocortical dysplasias in rats mimic numerous aspects of human polymicrogyria and are used as a model for the study of developmental migration disorders. Since memory tests have demonstrated learning deficits in rodents with neocortical malformations, we investigated the expression and properties of long-term potentiation (LTP) in neocortical slices from adult freeze-lesioned and control rats. Field potentials, recorded in layer II/III at a distance of 2-3 mm lateral to perinatally induced microgyri, were strongly enhanced following theta-burst stimulation in layer VI (amplitude: 174 +/- 4\%) compared to controls (110 +/- 2\%). In contrast, in layer IV of the freeze-lesioned cortex LTP could not reliably be induced. Histochemical analysis, performed to elucidate the cellular basis of the impaired plasticity, revealed diminished amounts of the GABAA-receptor subunit gamma2 in the paramicrogyral zone, likely representing a diminished GABA-ergic filter, which is thought to prevent LTP induced in layer VI under normal conditions. Cytochrome-oxidase staining after electrophysiological examination disclosed that LTP in layer IV of the freeze-lesioned cortex could only be elicited, when stimulation was applied within a preserved barrel cortex. Our study provides evidence that focal cryolesions during cortical development cause an impaired synaptic plasticity that may underlie learning disabilities.}, Author = {Peters, Oliver and Redecker, Christoph and Hagemann, Georg and Bruehl, Claus and Luhmann, Heiko J. and Witte, Otto W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Synapses;21 Epilepsy;Research Support, Non-U.S. Gov't;21 Neurophysiology;Long-Term Potentiation;Rats;Neuronal Plasticity;Comparative Study;research support, non-u.s. gov't ;Rats, Wistar;Animals, Newborn;Male;Animals;24 Pubmed search results 2008;Cerebral Cortex;comparative study}, Month = {10}, Nlm_Id = {9110718}, Number = {10}, Organization = {Department of Psychiatry and Psychotherapy, Charit{\'e}--University Medicine Berlin, Benjamin Franklin Campus, Eschenallee 3, D-14050 Berlin, Germany. oliver.peters\@charite.de}, Pages = {1081-7}, Pii = {bhh067}, Pubmed = {15115746}, Title = {Impaired synaptic plasticity in the surround of perinatally acquired [correction of aquired] dysplasia in rat cerebral cortex}, Uuid = {F939CE0D-CAD7-4E94-B879-86B90E803F51}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh067}} @book{Peters:1984, Abstract = {84001982 //r88 edited by Alan Peters and Edward G. Jones. ill. ; 26 cm. Vol. 2, 5- edited by Edward G. Jones and Alan Peters. v. 1. Cellular components of the cerebral cortex -- v. 2. Functional properties of cortial cells -- v. 3. Visual cortex -- v. 4. Association and auditory cortices -- v. 5. Sensory-motor areas and aspects of cortical connectivity -- v. 6. Further aspects of cortical function, including hippocampus -- v. 7. Development and maturation of cerebral cortex -- v. 8. Comparative structure and evolution of cerebral cortex, pt. 1-2. (2 v.) -- v. 9. Normal and altered states of function -- v. 12. Extrastriate cortex in primates -- v. 13. Models of cortical circuits.}, Author = {Peters, Alan and Jones, Edward G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Isbn = {0306415445}, Keywords = {Cerebral Cortex anatomy and histology.;M QP383 .C45 1984 WL 307 C4136 612/.825;Cerebral Cortex physiology.}, Publisher = {Plenum Press}, Title = {Cerebral cortex}, Uuid = {3507F63E-7E85-46E7-B1E9-C012563FE198}, Year = {1984}} @article{Peters:2004a, Abstract = {Complete envelope genes were amplified from autopsy brain tissue of five individuals who had died of AIDS and had neurological complications. Lymph node samples were included for two of the patients. Nineteen different envelope clones from the five patients had distinct V1V2 sequences. Thirteen of the envelopes were functional and conferred fusigenicity and infectivity for CD4(+) CCR5(+) cells. Infectivity and cell-cell fusion assays showed that most envelopes used both CCR5 and CCR3. One brain-derived envelope used a broad range of coreceptors, while three other brain envelopes from one individual were restricted to CCR5. However, there was no correlation between tissue of origin and coreceptor use. Envelopes showed two very distinct phenotypes depending on their capacity to infect macrophages and to exploit low levels of CD4 and/or CCR5 for infection. Envelopes that were highly fusigenic and tropic for macrophages were identified in brain tissue from four of the five patients. The enhanced macrophage tropism correlated with reduced sensitivity to inhibition by Q4120, a CD4-specific antibody, but not with sensitivity to the CCR5 inhibitor, TAK779. The highly macrophage-tropic envelopes were able to infect cells expressing low levels of CD4 and/or CCR5. Comparison with several well-characterized macrophage-tropic envelopes showed that the four identified patient envelopes were at the top limit of macrophage tropism. In contrast, all four lymph node-derived envelopes exhibited a non-macrophage-tropic phenotype and required high levels of CD4 for infection. Our data support the presence of envelopes that are highly fusigenic and tropic for macrophages in the brains of patients with neurological complications. These envelopes are able to infect cells that express low levels of CD4 and/or CCR5 and may have adapted for replication in brain macrophages and microglia, which are known to express limited amounts of CD4.}, Author = {Peters, Paul J. and Bhattacharya, Jayanta and Hibbitts, Samantha and Dittmar, Matthias T. and Simmons, Graham and Bell, Jeanne and Simmonds, Peter and Clapham, Paul R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Gene Products, env;HIV-1;Humans;Macrophages;Cells, Cultured;Phenotype;Brain;Cell Fusion;Antigens, CD4;Lymph Nodes;11 Glia;HIV Infections;Peptide Fragments;Research Support, U.S. Gov't, P.H.S.;Receptors, CCR5;Polymerase Chain Reaction;Amino Acid Sequence;Molecular Sequence Data;HIV Envelope Protein gp120;AIDS Dementia Complex}, Month = {7}, Nlm_Id = {0113724}, Number = {13}, Organization = {Program in Molecular Medicine and Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester MA 01605, USA.}, Pages = {6915-26}, Pii = {78/13/6915}, Pubmed = {15194768}, Title = {Biological analysis of human immunodeficiency virus type 1 R5 envelopes amplified from brain and lymph node tissues of AIDS patients with neuropathology reveals two distinct tropism phenotypes and identifies envelopes in the brain that confer an enhanced tropism and fusigenicity for macrophages}, Uuid = {6BA60E90-4892-41A1-811A-371BC898A9E2}, Volume = {78}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1128/JVI.78.13.6915-6926.2004}} @article{Petersen:2004a, Abstract = {We used two-channel three-dimensional time-lapse fluorescence confocal imaging in live rat hippocampal slice cultures (1-7 days in vitro) to determine the motility behaviors of activated microglia as they engage dead and dying cells following traumatic brain tissue injury. Live microglia were labeled with a fluorescently conjugated lectin (IB(4)), and dead neurons were labeled with a membrane-impermeant fluorescent DNA-binding dye (Sytox Orange or To-Pro-3). Tissue injury during the slicing procedure induced neuronal death and microglial activation, but the density of dead cells diminished approximately 10-fold by 7 days in vitro as resident microglia cleared dead cells. In time-lapse movies (4-20 h long), activated microglia exhibited varying levels of motile and locomotory activity. The motility of microglia could change abruptly following contact by other microglia or death of nearby cells. When neighboring cells died, some microglia rapidly moved toward or extended a process to engulf the dead cell, consistent with a chemotactic signaling response. Dead cell nuclei usually were engulfed and carried along by highly motile and locomoting microglia. The mean time to engulfment was approximately 5 times faster for newly deceased cells (33 min) than for extant dead cells (160 min), suggesting that the efficacy of microglial phagocytosis in situ might vary with time after cell death or mode of cell death. These observations demonstrate that activated microglia are heterogeneous with respect to motile activity following traumatic tissue injury and further indicate that cell motility in situ is temporally regulated at the single cell level, possibly by direct cell-cell contact and by diffusible substances emanating from nearby dead cells.}, Author = {Petersen, Mark A. and Dailey, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Phagocytosis;Animals;In Vitro;Rats;Microscopy, Confocal;Microglia;Cell Communication;Rats, Sprague-Dawley;Hippocampus;Cell Movement;Not relevant;11 Glia;Alpha;Support, Non-U.S. Gov't;Neurons;Cell Nucleus;Support, U.S. Gov't, P.H.S.;Cell Death}, Month = {4}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Biological Sciences, University of Iowa, Iowa City, Iowa, USA.}, Pages = {195-206}, Pubmed = {15042586}, Title = {Diverse microglial motility behaviors during clearance of dead cells in hippocampal slices}, Uuid = {EBCF3C42-7CBD-4B88-B9B0-9E4F09B7FCED}, Volume = {46}, Year = {2004}, url = {papers/Petersen_Glia2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10362}} @article{Petersen:2003, Abstract = {The spatiotemporal dynamics of the sensory response in layer 2/3 of primary somatosensory cortex evoked by a single brief whisker deflection was investigated by simultaneous voltage-sensitive dye (VSD) imaging and whole-cell (WC) voltage recordings in the anesthetized rat combined with reconstructions of dendritic and axonal arbors of L2/3 pyramids. Single and dual WC recordings from pyramidal cells indicated a strong correlation between the local VSD population response and the simultaneously measured subthreshold postsynaptic potential changes in both amplitude and time course. The earliest VSD response was detected 10-12 msec after whisker deflection centered above the barrel isomorphic to the stimulated principal whisker. It was restricted horizontally to the size of a single barrel-column coextensive with the dendritic arbor of barrel-column-related pyramids in L2/3. The horizontal spread of excitation remained confined to a single barrel-column with weak whisker deflection. With intermediate deflections, excitation spread into adjacent barrel-columns, propagating twofold more rapidly along the rows of the barrel field than across the arcs, consistent with the preferred axonal arborizations in L2/3 of reconstructed pyramidal neurons. Finally, larger whisker deflections evoked excitation spreading over the entire barrel field within approximately 50 msec before subsiding over the next approximately 250 msec. Thus the subthreshold cortical map representing a whisker deflection is dynamic on the millisecond time scale and strongly depends on stimulus strength. The sequential spatiotemporal activation of the excitatory neuronal network in L2/3 by a simple sensory stimulus can thus be accounted for primarily by the columnar restriction of L4 to L2/3 excitatory connections and the axonal field of barrel-related pyramids.}, Author = {Petersen, Carl C. H. and Grinvald, Amiram and Sakmann, Bert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Animals;Image Processing, Computer-Assisted;Rats;Afferent Pathways;Imaging, Three-Dimensional;Synaptic Transmission;Patch-Clamp Techniques;Axons;Kinetics;Pyramidal Cells;Thiazoles;Rats, Wistar;Microscopy, Fluorescence;Vibrissae;Dendrites;research support, non-u.s. gov't ;Nerve Net;Evoked Potentials, Somatosensory;21 Neurophysiology;Membrane Potentials;Somatosensory Cortex;Pyrazoles;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8102140}, Number = {4}, Organization = {Department of Cell Physiology, Max-Planck-Institute for Medical Research, Heidelberg D-69120, Germany. petersen\@mpimf-heidelberg.mpg.de}, Pages = {1298-309}, Pii = {23/4/1298}, Pubmed = {12598618}, Title = {Spatiotemporal dynamics of sensory responses in layer 2/3 of rat barrel cortex measured in vivo by voltage-sensitive dye imaging combined with whole-cell voltage recordings and neuron reconstructions}, Uuid = {5AECCD7F-488F-4CAC-AFB5-471F0E74C580}, Volume = {23}, Year = {2003}} @article{Petersen:2002, Abstract = {Neurons in most regions of the mammalian nervous system are generated over an extended period of time during development. Maintaining sufficient numbers of progenitors over the course of neurogenesis is essential to ensure that neural cells are produced in correct numbers and diverse types. The underlying molecular mechanisms, like those governing stem-cell self-renewal in general, remain poorly understood. We report here that mouse numb and numblike (Nbl), two highly conserved homologues of Drosophila numb, play redundant but critical roles in maintaining neural progenitor cells during embryogenesis, by allowing their progenies to choose progenitor over neuronal fates. In Nbl mutant embryos also conditionally mutant for mouse numb in the nervous system, early neurons emerge in the expected spatial and temporal pattern, but at the expense of progenitor cells, leading to a nearly complete depletion of dividing cells shortly after the onset of neurogenesis. Our findings show that a shared molecular mechanism, with mouse Numb and Nbl as key components, governs the self-renewal of all neural progenitor cells, regardless of their lineage or regional identities. 0028-0836 Journal Article}, Author = {Petersen, P. H. and Zou, K. and Hwang, J. K. and Jan, Y. N. and Zhong, W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:55 -0400}, Journal = {Nature}, Keywords = {10 Development;Cell Differentiation;Animals;Motor Neurons/*cytology/metabolism;Stem Cells/*cytology/metabolism;Gene Deletion;Time Factors;F both;Nerve Tissue Proteins/genetics/*metabolism;Support, Non-U.S. Gov't;Cell Lineage;Alleles;Mice, Knockout;Juvenile Hormones/genetics/*metabolism;Mice;Cell Division;Nervous System/cytology/*embryology/metabolism;Cell Death}, Number = {6910}, Organization = {Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.}, Pages = {929-34}, Title = {Progenitor cell maintenance requires numb and numblike during mouse neurogenesis}, Uuid = {EC6BB17C-9C2A-43B5-9322-D47CBF17F63D}, Volume = {419}, Year = {2002}, url = {papers/Petersen_Nature2002.pdf}} @article{Petersen:2004, Author = {Petersen, Carl C. H. and Brecht, Michael and Hahn, Thomas T. G. and Sakmann, Bert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {retraction of publication;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0404511}, Number = {5693}, Pages = {54}, Pii = {306/5693/54b}, Pubmed = {15459367}, Title = {Retraction}, Uuid = {5B5F01C4-8669-4E54-8BF6-FA42946099A2}, Volume = {306}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.306.5693.54b}} @article{Peterson:2004, Abstract = {Estrogens have neurotrophic and neuroprotective properties. The synthesis of estrogen occurs via the expression of aromatase. Previous studies have shown that injury to the vertebrate brain results in a rapid and dramatic up-regulation of aromatase expression in astrocytes around the lesion. As part of experiments examining injury-induced glial aromatization, we identified aromatase in radial glia of the zebra finch brain. Adult female zebra finches received a penetrating injury to the right hippocampus. Twenty-four hours after lesioning, birds were administered bromodeoxyuridine (BrdU) and sacrificed 2 hours, 1 day, or 7 days later. We determined the distribution of aromatase and BrdU labeling by using immunocytochemistry. Radial aromatase was localized to cells lining the lateral ventricle adjacent to the lesioned hippocampus. Injury also induced a dramatic accumulation of newly generated cells labeled with BrdU around the lesion. BrdU labeling was strongly associated with aromatase-positive radial fibers, suggesting the migration of newly generated cells along these fibers. In the songbird brain, estrogen supports neuronal recruitment and promotes the survival and addition of new neurons. The presence of aromatase in radial glia provides a mechanism of estrogen delivery to postmitotic cells. Radial aromatization may be a key feature in the repair of the vertebrate brain following neural injury.}, Author = {Peterson, Richard S. and Lee, Diane W. and Fernando, Gowry and Schlinger, Barney A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Cell Differentiation;Animals;Songbirds;Up-Regulation;Neuronal Plasticity;Neuroprotective Agents;Female;Antigens, Differentiation;Aromatase;Hippocampus;Wounds, Penetrating;Vimentin;Disease Models, Animal;Cell Movement;Nerve Regeneration;Brain Injuries;Research Support, U.S. Gov't, P.H.S.;Neuroglia;Neurons;Cell Division;24 Pubmed search results 2008;Stem Cells}, Month = {7}, Nlm_Id = {0406041}, Number = {2}, Organization = {Department of Physiological Science, University of California, Los Angeles, California 90095, USA. rsp\@ucla.edu}, Pages = {261-9}, Pubmed = {15211466}, Title = {Radial glia express aromatase in the injured zebra finch brain}, Uuid = {C8D1B639-E436-4C0D-8BB6-ED74834AA3CD}, Volume = {475}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20157}} @article{Petitto:2003, Abstract = {Following facial nerve axotomy in mice, T cells cross the intact blood-brain barrier (BBB), home to nerve cell bodies in the facial motor nucleus (FMN), and augment neuroregenerative processes. The pivotal T cell immunoregulatory cytokine, IL-2, appears to have bidirectional effects on neuronal and microglial cell function, suggesting rival hypotheses that IL-2 could either enhance or disrupt processes associated with regeneration of axotomized facial motor neurons. We tested these competing hypotheses by comparing the effect of facial nerve axotomy on C57BL/6-IL-2(-/-) knockout and C57BL/6-IL-2(+/+) wild-type littermates. Since IL-2 may also be produced endogenously in the brain, we also sought to determine whether differences between the knockout and wild-type mice were attributable to loss of IL-2 gene expression in the CNS, loss of peripheral sources of IL-2 and the associated effects on T cell function, or a combination of these factors. To address this question, we bred novel congenic mice with the SCID mutation (mice lacking T cell derived IL-2) that were homozygous for either the IL-2 knockout or wild-type gene alleles (C57BL/6scid-IL-2(-/-) and C57BL/6scid-IL-2(+/+) littermates, respectively). Groups were assessed for differences in (1) T lymphocytes entering the axotomized FMN; (2) perineuronal CD11b(+) microglial phagocytic clusters, a measure of motor neuron death; and (3) activated microglial cells as measured by MHC-II positivity. C57BL/6-IL-2(-/-) knockout mice had significantly higher numbers of T cells and lower numbers of activated MHC-II-positive microglial cells in the regenerating FMN than wild-type littermates, although the number of CD11b(+) phagocytic microglia clusters did not differ. Thus, despite the significant impairment of T cell function known to be associated with loss of peripheral IL-2, the increased number of T cells entering the axotomized FMN appears to have sufficient activity to support neuroregenerative processes. Congenic C57BL/6scid-IL-2(-/-) knockout mice had lower numbers of CD11b(+) microglial phagocytic clusters than congenic C57BL/6scid-IL-2(+/+) wild-type littermates, suggesting that loss of the IL-2 gene in the CNS (and possibly the loss of other unknown sources of the gene) enhanced neuronal regeneration. Further study of IL-2's complex actions in neuronal injury may provide greater understanding of key variables that determine whether or not immunological processes in the brain are proregenerative.}, Author = {Petitto, John M. and Huang, Zhi and Lo, Jeannette and Streit, Wolfgang J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {T-Lymphocytes;Lymphocyte Count;Animals;Microglia;Female;Mutation;Mice, SCID;Not relevant;Chemotaxis, Leukocyte;11 Glia;Male;Nerve Regeneration;Facial Nerve Injuries;Interleukin-2;Mice, Knockout;Support, U.S. Gov't, P.H.S.;Gliosis;Mice;Motor Neurons;Immunohistochemistry;Retrograde Degeneration;Facial Nerve;Histocompatibility Antigens Class II}, Medline = {22396249}, Month = {1}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Psychiatry, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, FL 32610-0256, USA. jpetitto\@ufl.edu}, Pages = {95-103}, Pii = {S0165572802004228}, Pubmed = {12507776}, Title = {IL-2 gene knockout affects T lymphocyte trafficking and the microglial response to regenerating facial motor neurons}, Uuid = {7A4103B8-FCA2-4576-B3AC-9B1842C5C060}, Volume = {134}, Year = {2003}} @article{Petreanu:2002, Abstract = {Young neurons born in the subventricular zone (SVZ) of adult mice migrate to the olfactory bulb (OB) where they differentiate into granule cells (GCs) and periglomerular interneurons. Using retroviral labeling of precursors in the SVZ, we describe five stages and the timing for the maturation of newly formed GCs: (1) tangentially migrating neuroblasts (days 2-7); (2) radially migrating young neurons (days 5-7); (3) GCs with a simple unbranched dendrite that does not extend beyond the mitral cell layer (days 9-13); (4) GCs with a nonspiny branched dendrite in the external plexiform layer (days 11-22); and (5) mature GCs (days 15-30). Using [3H]thymidine, we show that the maximum number of labeled GCs is observed around day 15 after injection. Interestingly, between days 15 and 45 after birth, soon after the cells developed spines, the number of [3H]thymidine-labeled GCs declined by 50\%. Using anosmic mice, we found that sensory input was critical for the survival of GCs from day 15 to 45 after labeling. However, the number and morphology of 15-d-old cells in the granule cell layer was similar in anosmic and wild-type mice. We infer that the lack of activity did not have an effect on the generation, migration, and early differentiation of granule cells. Soon after young GCs matured, and presumably became synaptically connected, their survival depended on the level of activity that they received. This selection mechanism might allow the construction of specific OB circuits based on olfactory experience and suggests possible functions of OB cell replacement. 1529-2401 Journal Article}, Author = {Petreanu, L. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Smell;Cell Survival;Cell Death/*physiology;Aging/physiology;Male;Lateral Ventricles/cytology;Animals;B pdf;Smell/*physiology;Research Support, U.S. Gov't, P.H.S.;Cell Movement;Bromodeoxyuridine;Stem Cells/cytology;Cell Division;Mice, Inbred C57BL;Cell Differentiation/physiology;Lateral Ventricles;Olfactory Bulb;Dendrites;Neurons/classification/*cytology/*physiology;Support, U.S. Gov't, P.H.S.;Dendrites/physiology/ultrastructure;Aging;02 Adult neurogenesis migration;Cell Death;Cell Movement/physiology;Stem Cells;Mice, Knockout;Olfaction Disorders;Mice;Olfactory Bulb/*cytology/*physiology;Neurons;Olfaction Disorders/physiopathology}, Medline = {22117915}, Month = {7}, Nlm_Id = {8102140}, Number = {14}, Organization = {The Rockefeller University, New York, New York 10021, USA.}, Pages = {6106-13}, Pii = {22/14/6106}, Pubmed = {12122071}, Title = {Maturation and death of adult-born olfactory bulb granule neurons: role of olfaction}, Uuid = {33D7490E-5DF8-4FE9-A103-50F695FA7B80}, Volume = {22}, Year = {2002}, url = {papers/Petreanu_JNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/20026588}} @article{Petridis:2004, Abstract = {Expression of polysialic acid (PSA) promotes migration of progenitor cells from the subventricular zone (SVZ) to the olfactory bulb, where they differentiate into interneurons. This differentiation has been found to coincide with a loss of PSA. Moreover, specific removal of PSA from the mouse SVZ by endoneuraminidase-N was found to cause premature differentiation, as evidenced by neurite outgrowth and tyrosine hydroxylase synthesis in vivo and by expression of neurofilament-L and betaIII-tubulin in SVZ explant cultures. This differentiation involved activation of mitogen-activated protein kinase through p59fyn and was blocked by its inhibition. The effects of PSA removal were found to be cell contact-dependent and to be reduced by anti-neural cell adhesion molecule antibodies. These findings indicate that PSA expression regulates the fate of SVZ precursors by two contact-dependent mechanisms, the previously reported reduction in cell-cell adhesion that allows cell translocation, and the postponement of cell differentiation that otherwise would be induced by signals generated through surface molecule-mediated cell-cell interactions. Developmental Dynamics 230:675-684, 2004. 1058-8388 Journal Article}, Author = {Petridis, A. K. and El Maarouf, A. and Rutishauser, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Dev Dyn}, Keywords = {02 Adult neurogenesis migration;B, C pdf}, Number = {4}, Organization = {Cellular and Developmental Neuroscience, Program in Cell Biology, Memorial Sloan-Kettering Cancer Center, New York, New York.}, Pages = {675-84}, Title = {Polysialic acid regulates cell contact-dependent neuronal differentiation of progenitor cells from the subventricular zone}, Uuid = {9753D88D-9E6F-4031-BFF4-84714B5DE81A}, Volume = {230}, Year = {2004}, url = {papers/Petridis_DevDyn2004.pdf}} @article{Petritsch:2003, Abstract = {Asymmetric cell divisions generate cellular diversity. In Drosophila, embryonic neuroblasts target cell fate determinants basally, rotate their spindles by 90 degrees to align with the apical-basal axis, and divide asymmetrically in a stem cell-like fashion. In this process, apically localized Bazooka recruits Inscuteable and other proteins to form an apical complex, which then specifies spindle orientation and basal localization of the cell fate determinants and their adapter proteins such as Miranda. Here we report that Miranda localization requires the unconventional myosin VI Jaguar (Jar). In jar null mutant embryos, Miranda is delocalized and the spindle is misoriented, but the Inscuteable crescent remains apical. Miranda directly binds to Jar, raising the possibility that Miranda and its associated proteins are translocated basally by this actin-based motor. Our studies demonstrate that a class VI myosin is necessary for basal protein targeting and spindle orientation in neuroblasts. 1534-5807 Journal Article}, Author = {Petritsch, C. and Tavosanis, G. and Turck, C. W. and Jan, L. Y. and Jan, Y. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Dev Cell}, Keywords = {Cell Cycle Proteins/metabolism;Neurons/*physiology;Myosin Heavy Chains/*physiology;Animals;10 Development;Immunoenzyme Techniques;Drosophila Proteins/*physiology;Biological Transport;Mitotic Spindle Apparatus/*physiology;Drosophila melanogaster/*embryology/genetics;Cell Movement;Cell Polarity;RNA Interference;Immunoblotting;Support, Non-U.S. Gov't;Cytoskeletal Proteins/metabolism;Carrier Proteins/metabolism;Cell Division/physiology;Embryo, Nonmammalian/cytology;Support, U.S. Gov't, Non-P.H.S.;Cell Differentiation/physiology;F}, Number = {2}, Organization = {Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.}, Pages = {273-81}, Pubmed = {12586070}, Title = {The Drosophila myosin VI Jaguar is required for basal protein targeting and correct spindle orientation in mitotic neuroblasts}, Uuid = {C93A147F-4731-46EA-B42B-65412832A4A7}, Volume = {4}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12586070}} @article{Petruska:1997, Abstract = {The alpha-D-galactose specific isolectin I-B4 from Griffonia simplicifolia (GS-I-B4) labels CNS microglia and certain peripheral neurons, including a subpopulation of small dark, type B dorsal root ganglion cells, some post-ganglionic sympathetic axons, and nearly all peripheral gustatory axons. The innervation patterns of GS-I-B4 reactive sensory ganglion cells are unknown for many peripheral target tissues, including their probable primary target, the skin. The present study describes the distribution of GS-I-B4 reactive axons in hairy and glabrous hindpaw skin and in the glans penis of rats, using both single and double-labelling histochemical techniques. Neuronal processes were identified using (1) histochemistry with horseradish peroxidase conjugated GS-I-B4 or (2) immunohistochemistry against PGP 9.5 to identify all axons, and biotinylated lectin histochemistry with avidin-FITC to identify the subpopulation of GS-I-B4 reactive axons. GS-I-B4 strongly labelled unmyelinated cutaneous sensory afferents, as well as some sympathetic efferents and visceral afferents. lectin reactive axons were seen to innervate the upper hair shaft epidermis in hairy skin, and were abundant in the shallow dermis in hairy and glabrous skin and glans penis. Lectin reactive axons were also abundant in the lamina propria and distal urethral epithelium of the penis. These results provide new evidence for the cutaneous sensory role of GS-I-B4 reactive primary afferents, as well as evidence to support the contention that the lectin is a specific marker for a subpopulation of unmyelinated axons and not simply a marker for the myelination state of an axon.}, Author = {Petruska, J. C. and Streit, W. J. and Johnson, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0899-0220}, Journal = {Somatosens Mot Res}, Keywords = {Animals;Rats;Immunoenzyme Techniques;Penis;Female;Neurons, Afferent;Rats, Sprague-Dawley;Axons;Not relevant;11 Glia;Mechanoreceptors;Skin;Male;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Nerve Fibers;Lectins;Peripheral Nerves}, Medline = {97385711}, Nlm_Id = {8904127}, Number = {1}, Organization = {Department of Neuroscience, University of Florida, Gainesville 32610, USA.}, Pages = {17-26}, Pubmed = {9241725}, Title = {Localization of unmyelinated axons in rat skin and mucocutaneous tissue utilizing the isolectin GS-I-B4}, Uuid = {3B4C9BDA-B456-4DE6-8569-FD055513A3B9}, Volume = {14}, Year = {1997}} @article{Pham:1999, Abstract = {Neuronal activity-dependent processes are believed to mediate the formation of synaptic connections during neocortical development, but the underlying intracellular mechanisms are not known. In the visual system, altering the pattern of visually driven neuronal activity by monocular deprivation induces cortical synaptic rearrangement during a postnatal developmental window, the critical period. Here, using transgenic mice carrying a CRE-lacZ reporter, we demonstrate that a calcium- and cAMP-regulated signaling pathway is activated following monocular deprivation. We find that monocular deprivation leads to an induction of CRE-mediated lacZ expression in the visual cortex preceding the onset of physiologic plasticity, and this induction is dramatically downregulated following the end of the critical period. These results suggest that CRE-dependent coordinate regulation of a network of genes may control physiologic plasticity during postnatal neocortical development.}, Author = {Pham, T. A. and Impey, S. and Storm, D. R. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Aging;Sensory Deprivation;Visual Cortex;research support, non-u.s. gov't;Cyclic AMP;21 Neurophysiology;Geniculate Bodies;Neuronal Plasticity;Calcium;Transcription, Genetic;Mice, Transgenic;Cyclic AMP Response Element-Binding Protein;research support, u.s. gov't, p.h.s.;Animals;Mice;24 Pubmed search results 2008;Vision, Monocular}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Physiology, The W.M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco 94143, USA. tpham\@phy.ucsf.edu}, Pages = {63-72}, Pii = {S0896-6273(00)80679-0}, Pubmed = {10027290}, Title = {CRE-mediated gene transcription in neocortical neuronal plasticity during the developmental critical period}, Uuid = {CFE4E2F4-2ED2-40D1-A507-94AA41C8FEDD}, Volume = {22}, Year = {1999}, url = {papers/Pham_Neuron1999.pdf}} @article{Pham:2001, Abstract = {The development of precise connections in the mammalian brain proceeds through refinement of initially diffuse patterns, a process that occurs largely within critical developmental windows. To elucidate the molecular pathways that orchestrate these early periods of circuit remodeling, we have examined the role of a calcium- and cAMP-regulated transcriptional pathway. We show that there is a window of CRE/CREB-mediated gene expression in the developing thalamus, which precedes neocortical expression. In the LGN, this wave of gene expression occurs prior to visual experience, but requires retinal function. Mutant mice with reduced CREB expression show loss of refinement of retinogeniculate projections. These results suggest an important role of the CRE/CREB transcriptional pathway in the coordination of experience-independent circuit remodeling during forebrain development.}, Author = {Pham, T. A. and Rubenstein, J. L. and Silva, A. J. and Storm, D. R. and Stryker, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Retina;Viral Proteins;Heterozygote;beta-Galactosidase;Animals;Gene Expression Regulation, Developmental;Aging;Visual Pathways;Female;Integrases;Mice, Transgenic;Axons;Mice, Inbred C57BL;research support, non-u.s. gov't;Crosses, Genetic;Male;Cyclic AMP Response Element-Binding Protein;Thalamus;Eye Enucleation;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Mice;24 Pubmed search results 2008;Geniculate Bodies;Transcription, Genetic}, Month = {8}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Psychiatry and Behavioral Sciences, Graduate Program in Neurobiology and Behavior, University of Washington School of Medicine, Seattle, WA 98195, USA. tonypham\@u.washington.edu}, Pages = {409-20}, Pii = {S0896-6273(01)00381-6}, Pubmed = {11516398}, Title = {The CRE/CREB pathway is transiently expressed in thalamic circuit development and contributes to refinement of retinogeniculate axons}, Uuid = {44FA583E-B9CA-489C-BF10-281EDEDB900D}, Volume = {31}, Year = {2001}} @article{Philippe:2006, Abstract = {Lentivirus-derived vectors are among the most promising viral vectors for gene therapy currently available, but their use in clinical practice is limited by the associated risk of insertional mutagenesis. We have overcome this problem by developing a nonintegrative lentiviral vector derived from HIV type 1 with a class 1 integrase (IN) mutation (replacement of the 262RRK motif by AAH). We generated and characterized HIV type 1 vectors carrying this deficient enzyme and expressing the GFP or neomycin phosphotransferase transgene (NEO) under control of the immediate early promoter of human CMV. These mutant vectors efficiently transduced dividing cell lines and nondividing neural primary cultures in vitro. After transduction, transient GFP fluorescence was observed in dividing cells, whereas long-term GFP fluorescence was observed in nondividing cells, consistent with the viral genome remaining episomal. Moreover, G418 selection of cells transduced with vectors expressing the NEO gene showed that residual integration activity was lower than that of the intact IN by a factor of 500-1,250. These nonintegrative vectors were also efficient in vivo, allowing GFP expression in mouse brain cells after the stereotactic injection of IN-deficient vector particles. Thus, we have developed a generation of lentiviral vectors with a nonintegrative phenotype of great potential value for secure viral gene transfer in clinical applications.}, Author = {Philippe, St{\'e}phanie and Sarkis, Chamsy and Barkats, Martine and Mammeri, Hamid and Ladroue, Charline and Petit, Caroline and Mallet, Jacques and Serguera, Che}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, non-u.s. gov't;15 Retrovirus mechanism;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {7505876}, Number = {47}, Organization = {Laboratoire de G{\'e}n{\'e}tique Mol{\'e}culaire de la Neurotransmission et des Processus Neurod{\'e}g{\'e}n{\'e}ratifs, Universit{\'e} Pierre et Marie Curie Paris 6, Centre National de la Recherche Scientifique, Unit{\'e} Mixte de Recherche 7091, 83 bd de l'H\^{o}pital, 75013 Paris, France.}, Pages = {17684-9}, Pii = {0606197103}, Pubmed = {17095605}, Title = {Lentiviral vectors with a defective integrase allow efficient and sustained transgene expression in vitro and in vivo}, Uuid = {4723949C-1085-44F9-9E3D-6992CF26548F}, Volume = {103}, Year = {2006}, url = {papers/Philippe_ProcNatlAcadSciUSA2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0606197103}} @article{Piacibello:2002, Abstract = {The ability of advanced-generation lentiviral vectors to transfer the green fluorescent protein (GFP) gene into human hematopoietic stem cells (HSCs) was studied in culture conditions that allowed expansion of transplantable human HSCs. Following 96 hours' exposure to flt3/flk2 ligand (FL), thrombopoietin (TPO), stem cell factor (SCF), and interleukin-6 (IL-6) and overnight incubation with vector particles, cord blood (CB) CD34(+) cells were further cultured for up to 4 weeks. CD34(+) cell expansion was similar for both transduced and control cells. Transduction efficiency of nonobese diabetic/severe combined immunodeficient (NOD/SCID) repopulating cells (SRCs) was assessed by transplants into NOD/SCID mice. Mice that received transplants of transduced week 1 and week 4 expanded cells showed higher levels of human engraftment than mice receiving transplants of transduced nonexpanded cells (with transplants of 1 x 10(5) CD34(+) cells, the percentages of CD45(+) cells were 20.5 +/- 4.5 [week 1, expanded] and 27.2 +/- 8.2 [week 4, expanded] vs 11.7 +/- 2.5 [nonexpanded]; n = 5). The GFP(+)/CD45(+) cell fraction was similar in all cases (12.5\%+/- 2.9\%and 12.2\%+/- 2.7\%vs 12.7\%+/- 2.1\%). Engraftment was multilineage, with GFP(+)/lineage(+) cells. Clonality analysis performed on the bone marrow of mice receiving transduced and week 4 expanded cells suggested that more than one integrant likely contributed to the engraftment of GFP-expressing cells. Serial transplantations were performed with transduced week 4 expanded CB cells. Secondary engraftment levels were 10.7\%+/- 4.3\%(n = 12); 19.7\%+/- 6.2\%of human cells were GFP(+). In tertiary transplants the percentage of CD45(+) cells was lower (4.3\%+/- 1.7\%; n = 10); 14.8\%+/- 5.9\%of human cells were GFP(+), and human engraftment was multilineage. These results show that lentiviral vectors efficiently transduce HSCs, which can undergo expansion and maintain proliferation and self-renewal ability.}, Author = {Piacibello, Wanda and Bruno, Stefania and Sanavio, Fiorella and Droetto, Sara and Gunetti, Monica and Ailles, Laurie and Santoni de Sio, Francesca and Viale, Andrea and Gammaitoni, Loretta and Lombardo, Angelo and Naldini, Luigi and Aglietta, Massimo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Antigens, CD45;Mice, Inbred NOD;HIV-1;Hematopoietic Cell Growth Factors;Colony-Forming Units Assay;Animals;Transfection;Transplantation, Heterologous;Humans;Recombinant Proteins;Cells, Cultured;Mice, SCID;11 Glia;Immunophenotyping;Time Factors;Green Fluorescent Proteins;Genetic Vectors;Cell Lineage;Gene Therapy;Cord Blood Stem Cell Transplantation;Mice;Hematopoietic Stem Cells;Luminescent Proteins;Genes, Reporter;Cell Division;Graft Survival;Clone Cells;Research Support, Non-U.S. Gov't}, Medline = {22340756}, Month = {12}, Nlm_Id = {7603509}, Number = {13}, Organization = {Department of Oncological Sciences, University of Torino Medical School, Torino, Italy. wanda.piacibello\@ircc.it}, Pages = {4391-400}, Pii = {100/13/4391}, Pubmed = {12453876}, Title = {Lentiviral gene transfer and ex vivo expansion of human primitive stem cells capable of primary, secondary, and tertiary multilineage repopulation in NOD/SCID mice. Nonobese diabetic/severe combined immunodeficient}, Uuid = {9E580E96-D147-4565-B0C3-B2D64AC0D4F1}, Volume = {100}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood.V100.13.4391}} @article{Picard-Riera:2004, Abstract = {Mitotic activity persists in various regions of the adult mammal CNS. While evidences of neurogenesis appeared, many studies focused on the features of the adult stem cells from germinative areas such as the subventricular zone of the lateral ventricles, the dentate gyrus of the hippocampus, the cortex, the fourth ventricle and the central canal of the spinal cord. In the present paper, we review the potentialities of the adult germinative areas in terms of proliferation, migration and differentiation in non pathological situation and in response to different type of CNS injury. Adult endogenous stem cells are activated in response to various injuries but their capacities to migrate and to undergo either neurogenesis or gliogenesis differ according to the lesion-type and the germinative zone from which they arise. Different works demonstrated that epigenic factors such as growth factors can enhance the repair potential of the adult stem cells. Reactivation and mobilization of endogenous stem cells as well as demonstration of their long-term survival and functionality appear to be interesting strategies to investigate in order to promote endogenous repair of the adult CNS.}, Author = {Picard-Riera, Nathalie and Nait-Oumesmar, Brahim and Baron-Van Evercooren, Anne}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Stem Cell Transplantation;Research Support, Non-U.S. Gov't;Central Nervous System;Wound Healing;Nerve Regeneration;Stem Cells;Growth Substances;22 Stem cells;review, tutorial;Tissue Therapy;Humans;Animals;review;Brain Injuries}, Month = {4}, Nlm_Id = {7600111}, Number = {2}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, U546, Laboratoire des Affections de la My{\'e}line et des Canaux Ioniques Musculaires, Institut F{\'e}d{\'e}ratif des Neurosciences, CHU Piti{\'e}-Salp\^{e}tri\`{e}re, Paris, France.}, Pages = {223-31}, Pubmed = {15048920}, Title = {Endogenous adult neural stem cells: limits and potential to repair the injured central nervous system}, Uuid = {71C377B0-9C8A-4897-8FC2-D9EC2745E6B0}, Volume = {76}, Year = {2004}, url = {papers/Picard-Riera_JNeurosciRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20040}} @article{Pickard:2002, Abstract = {Intravitreal injection of the attenuated strain of pseudorabies virus (PRV Bartha) results in transneuronal spread of virus to a restricted set of central nuclei in the rat and mouse. We examined the pattern of central infection in the golden hamster after intravitreal inoculation with a recombinant strain of PRV Bartha constructed to express enhanced green fluorescent protein (PRV 152). Neurons in a subset of retinorecipient nuclei [i.e., suprachiasmatic nucleus (SCN), intergeniculate leaflet, olivary pretectal nucleus (OPN), and lateral terminal nucleus] and autonomic nuclei [i.e., paraventricular hypothalamic nucleus and Edinger-Westphal nucleus (EW)] are labeled by late stages of infection. Infection of the EW precedes infection in retinorecipient structures, raising the possibility that the SCN becomes infected by retrograde transsynaptic infection via autonomic (i.e., EW) circuits. We tested this hypothesis in two ways: (1) by removing the infected eye 24 hr after PRV 152 inoculation, well before viral infection first appears in the SCN; and (2) by examining central infection after intravitreal PRV 152 injection in animals with ablation of the EW. The pattern and time course of central infection were unchanged after enucleation, whereas EW ablation before intravitreal inoculation eliminated viral infection in the SCN. The results of EW lesions along with known connections between EW, OPN, and SCN indicate that intravitreal injection of PRV Bartha produces a retrograde infection of the autonomic innervation of the eye, which subsequently labels a restricted set of retinorecipient nuclei via retrograde trans-synaptic infection. These results, taken together with other genetic data, indicate that the mutations in PRV Bartha render the virus incapable of anterograde transport. PRV Bartha is thus a retrograde transsynaptic marker in the CNS. 1529-2401 Journal Article}, Author = {Pickard, G. E. and Smeraski, C. A. and Tomlinson, C. C. and Banfield, B. W. and Kaufman, J. and Wilcox, C. L. and Enquist, L. W. and Sollars, P. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Neurosci}, Keywords = {Hamsters;Animals;Suprachiasmatic Nucleus/pathology/*virology;Disease Progression;Synapses/pathology/virology;J abstr;Biological Transport;Herpesvirus 1, Suid/genetics/*growth &development;15 Retrovirus mechanism;Pseudorabies/pathology/*virology;Neurons/pathology/virology;Vitreous Body/*virology;Mesocricetus;Eye Enucleation;Visual Pathways/pathology/virology;Autonomic Nervous System/pathology/*virology;Support, U.S. Gov't, P.H.S.;*Axonal Transport/physiology;Genes, Reporter;Retinal Ganglion Cells/pathology/virology;Luminescent Proteins/genetics}, Number = {7}, Organization = {Department of Anatomy, Colorado State University, Fort Collins, Colorado 80523, USA. gpickard\@lamar.colostate.edu}, Pages = {2701-10}, Pubmed = {11923435}, Title = {Intravitreal injection of the attenuated pseudorabies virus PRV Bartha results in infection of the hamster suprachiasmatic nucleus only by retrograde transsynaptic transport via autonomic circuits}, Uuid = {1E3D6FB0-3360-44B2-8694-D69A59896EEE}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11923435}} @article{Picken-Bahrey:2003, Abstract = {Voltage- and current-clamp recordings were made from acute slices of mouse cerebral cortex from embryonic day 14 to postnatal day 17. We targeted cells in the migratory population of the embryonic intermediate zone (IZ) and in deep layers of embryonic and postnatal cortical plate (CP). IZ neurons maintain fairly consistent properties through the embryonic period, all expressing high-input resistance, inward Na(+) currents and outward K(+) currents, and none showing any hyperpolarization-activated currents. In CP neurons, several changes in physiological properties occur in the late embryonic and early postnatal period: inward Na(+) current density is strongly upregulated while outward K(+) current density remains almost unchanged, input resistance drops dramatically, and a hyperpolarization-activated current resembling I(h) appears. As a result of these changes, the action potential becomes larger, shorter in duration, and its threshold shifts to more negative potentials. In addition, CP cells become capable of firing repetitively and an increasing fraction show spontaneous action potentials. This coordinated development of ion channel properties may help to time the occurrence of developmentally relevant spontaneous activity in the immature cortex.}, Author = {Picken Bahrey, Heidi L. and Moody, William J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Potassium Channels;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;Female;Mice, Inbred C57BL;Pyramidal Cells;Sodium Channels;21 Circuit structure-function;Pregnancy;Animals;Mice;24 Pubmed search results 2008;Cerebral Cortex;Patch-Clamp Techniques}, Month = {4}, Nlm_Id = {0375404}, Number = {4}, Organization = {Department of Zoology, University of Washington, Seattle, Washington 98195, USA.}, Pages = {1761-73}, Pii = {00972.2002}, Pubmed = {12611962}, Title = {Early development of voltage-gated ion currents and firing properties in neurons of the mouse cerebral cortex}, Uuid = {7BDABA1F-BED1-4655-B5BE-26BBEB7E5755}, Volume = {89}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00972.2002}} @article{Pielak:2004, Abstract = {Initial studies suggested that spatial organization of the putative polar body contractile ring was determined by the peripheral aster in Spisula [Biol. Bull. 205 (2003) 192]. Here we report detailed supporting observations, including testing of aster and ring function with inhibitors. The metaphase peripheral aster was confirmed to spread cortically in an umbrella-like pattern, with microtubule-poor center. The aster disassembled during anaphase, leaving the spindle docked at the F-actin-poor center of a newly generated cortical F-actin ring that closely approximated the aster in location, measured diameter range, and pattern. Cytochalasin D and latrunculin-B permitted all events except ring and polar body formation. Nocodazole disassembly or taxol stabilization of the peripheral aster produced poorly defined rings or bulging anaphase asters within the ring center, respectively, inhibiting polar body formation. Polar body extrusion occurred at the ring center, the diameter of which diminished. Ring contractility-previously assumed-was verified using blebbistatin, a myosin-II ATPase inhibitor that permitted ring assembly but blocked polar body extrusion. The data support the hypothesis that peripheral aster spreading, perhaps dynein-driven, is causally related to polar body contractile ring formation, with anaphase entry and aster disassembly also required for polar body biogenesis. Previously reported astral spreading during embryonic micromere formation suggests that related mechanisms are involved in asymmetric somatic cytokinesis. 0012-1606 Journal Article}, Author = {Pielak, R. M. and Gaysinskaya, V. A. and Cohen, W. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Dev Biol}, Keywords = {EE pdf;Actins/chemistry;08 Aberrant cell cycle;Cytoskeleton/chemistry;Cell Division;Support, U.S. Gov't, Non-P.H.S.;Microtubules/chemistry;Centrosome/physiology;Animals;Support, Non-U.S. Gov't;Clams/*embryology;Myosin Type II/metabolism}, Number = {2}, Organization = {Department of Biological Sciences, Hunter College, New York, NY 10021, USA.}, Pages = {421-32}, Title = {Formation and function of the polar body contractile ring in Spisula}, Uuid = {804B1380-C789-42DA-AA21-71436098A258}, Volume = {269}, Year = {2004}, url = {papers/Pielak_DevBiol2004.pdf}} @article{Pinaudeau:2000, Abstract = {In order to determine the embryonic age at which the hodological phenotype developed by neocortical cells is specified, we have examined the spinal or tectal projections developed by embryonic (E) grafts of presumptive frontal or occipital neocortex placed into the frontal or occipital neocortex of newborn host rats. Grafts of E13, E14 and E16 cells of the frontal cortex transplanted into the occipital cortex of newborns are capable of developing and maintaining in adulthood a spinal cord axon. Grafts of E12 cells do not project to the spinal cord but send fibres to the superficial layers of the tectum. In addition, following transplantation into the frontal cortex, early embryonic (E12) cells from the presumptive occipital cortex are capable of differentiating into neurons with spinal cord projection but are practically incapable of developing a tectal projection. When grafted at E14 into the frontal cortex, occipital cells lose the capacity to project to the spinal cord but become able to send fibres to the tectum. Taken together, these findings indicate that young (E12) embryonic frontal and occipital cortical cells are competent to subsequently differentiate into neurons projecting to the spinal cord or tectum according to instructive signals available in the cortical territory where they complete their development. By E13/E14, some cortical cells are specified and their capacity to contact targets that are not appropriate to their embryonic origin is much reduced. These findings are consistent with the notion that cortical specification involves progressive restriction in cell multipotentiality and fate specification toward region-specific phenotypes.}, Author = {Pinaudeau, C. and Gaillard, A. and Roger, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Superior Colliculus;Research Support, Non-U.S. Gov't;Brain Tissue Transplantation;Rats;Neural Pathways;Cholera Toxin;Occipital Lobe;Pyramidal Tracts;Animals, Newborn;Graft Survival;Animals;24 Pubmed search results 2008;Fetal Tissue Transplantation;Frontal Lobe}, Medline = {20406012}, Month = {7}, Nlm_Id = {8918110}, Number = {7}, Organization = {CNRS: UMR 6558, D{\'e}partement des Neurosciences, Universit{\'e} de Poitiers, France.}, Pages = {2486-96}, Pii = {ejn148}, Pubmed = {10947824}, Title = {Stage of specification of the spinal cord and tectal projections from cortical grafts}, Uuid = {C0B579D3-0DA7-4E27-93DB-F0B674F50CA5}, Volume = {12}, Year = {2000}} @article{Pinching:1971, Author = {Pinching, A. J. and Powell, T. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0021-9533}, Journal = {J Cell Sci}, Keywords = {Synapses;Glycogen;Cell Membrane;Neuroglia;Dendrites;13 Olfactory bulb anatomy;Limbic System;Microscopy, Electron;Rats;Nerve Endings;Ribosomes;Animals;Cytoplasmic Granules;Cytoplasm;Axons}, Medline = {72053370}, Month = {9}, Nlm_Id = {0052457}, Number = {2}, Pages = {379-409}, Pubmed = {5124504}, Title = {The neuropil of the periglomerular region of the olfactory bulb}, Uuid = {FBEC1778-D067-11DA-8A8C-000D9346EC2A}, Volume = {9}, Year = {1971}} @article{Pinson:1973, Author = {Pinson, L. and Isaacson, R. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {24 Pubmed search results 2008;Mathematics;Electroencephalography;21 Neurophysiology;Rats;Action Potentials;Seizures;Penicillin G;Fourier Analysis;Disease Models, Animal;Brain;Cerebral Cortex;Animals;21 Epilepsy}, Medline = {74006936}, Month = {9}, Nlm_Id = {2983306R}, Number = {3}, Pages = {335-45}, Pubmed = {4517810}, Title = {Propagation of epileptiform activity in the brain examined by frequency-wavenumber analysis}, Uuid = {81887C56-69DF-4D9B-BEDD-AE1ED070B6D1}, Volume = {14}, Year = {1973}} @article{Pinto:2005, Abstract = {Waves of epileptiform activity in neocortex have three phenomenological stages: initiation, propagation, and termination. We use a well studied model of epileptiform activity in vitro to investigate directly the hypothesis that each stage is governed by an independent mechanism within the underlying cortical circuit. Using the partially disinhibited neocortical slice preparation, activity is induced and modulated using neurotransmitter receptor antagonists and is measured using both intracellular recordings and a linear array of extracellular electrodes. We find that initiation depends on both synaptic excitation and inhibition and entails a slow process of recruitment at discrete spatial locations within cortical layer 5 but not layer 2/3. Propagation depends on synaptic excitation but not inhibition and is a fast process that involves neurons across the spatial extent of the slice and in all cortical layers. Termination is modulated by synaptic excitation and inhibition. In space, termination occurs reliably at discrete locations. In time, termination is characterized by a strong depolarizing shift (block) and recovery of neurons in all cortical layers. These results suggest that the phenomenological stages of epileptiform events correspond to distinct mechanistic stages.}, Author = {Pinto, David J. and Patrick, Saundra L. and Huang, Wendy C. and Connors, Barry W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Epilepsy;Research Support, Non-U.S. Gov't;Rats, Sprague-Dawley;21 Neurophysiology;Rats;Research Support, U.S. Gov't, P.H.S.;Neocortex;In Vitro;Research Support, N.I.H., Extramural;Evoked Potentials;Pertussis Toxin;Electrophysiology;Disease Models, Animal;Animals;Thalamus;24 Pubmed search results 2008;21 Epilepsy}, Month = {9}, Nlm_Id = {8102140}, Number = {36}, Organization = {Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA. david\_pinto\@urmc.rochester.edu}, Pages = {8131-40}, Pii = {25/36/8131}, Pubmed = {16148221}, Title = {Initiation, propagation, and termination of epileptiform activity in rodent neocortex in vitro involve distinct mechanisms}, Uuid = {4E16ED41-B720-4BED-B58B-DA36D698352E}, Volume = {25}, Year = {2005}, url = {papers/Pinto_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2278-05.2005}} @article{Pitcher:2007, Abstract = {Extensive research has demonstrated that several specialized cortical regions respond preferentially to faces. One such region, located in the inferior occipital gyrus, has been dubbed the occipital face area (OFA). The OFA is the first stage in two influential face-processing models, both of which suggest that it constructs an initial representation of a face, but how and when it does so remains unclear. The present study revealed that repetitive transcranial magnetic stimulation (rTMS) targeted at the right OFA (rOFA) disrupted accurate discrimination of face parts but had no effect on the discrimination of spacing between these parts. rTMS to left OFA had no effect. A matched part and spacing discrimination task that used house stimuli showed no impairment. In a second experiment, rTMS to rOFA replicated the face-part impairment but did not produce the same effect in an adjacent area, the lateral occipital cortex. A third experiment delivered double pulses of TMS separated by 40 ms at six periods after stimulus presentation during face-part discrimination. Accuracy dropped when pulses were delivered at 60 and 100 ms only. These findings indicate that the rOFA processes face-part information at an early stage in the face-processing stream.}, Author = {Pitcher, David and Walsh, Vincent and Yovel, Galit and Duchaine, Bradley}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {9107782}, Number = {18}, Organization = {Institute of Cognitive Neuroscience, Department of Psychology, University College London, Alexandra House, 17 Queen Square, London WC1N 3AR, United Kingdom. d.pitcher\@ucl.ac.uk}, Pages = {1568-73}, Pii = {S0960-9822(07)01781-2}, Pubmed = {17764942}, Title = {TMS evidence for the involvement of the right occipital face area in early face processing}, Uuid = {E76F4E9A-79AF-4F27-AEA3-38351A926E43}, Volume = {17}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2007.07.063}} @article{Pixley:1998, Abstract = {The rate of neurogenesis in the peripheral olfactory neuroepithelium is regulated by unknown mechanisms. The members of the insulin-like growth factor (IGF) family can influence neuronal generation, survival and/or differentiation. Several members of this family, in particular IGF-1, are expressed at high levels in the olfactory bulb and epithelium, where they could influence the generation and/or survival of olfactory receptor neurons (ORNs). To explore the role of IGF-1 in the olfactory epithelium (OE), we asked which cells expressed IGF-1 receptors (IGF- 1Rs), using olfactory cell cultures and cryostat-cut tissue sections of neonatal (postnatal day four) and adult rat OE. An antibody specific for the alpha subunit of the IGF-1R densely labeled a subset of ORNs but not other cell types in sections and cultures. These ORNs were primarily immature, as determined by double labeling with neuronal markers. The number of IGF-1R-labeled cells as well as the levels of IGF-1R protein (determined by immunoprecipitation and Western blotting) decreased with age, which is consistent with normal developmental changes. To study IGF-1 effects in the intact animal, we infused IGF-1 and related growth factors into the noses of newborn Sprague-Dawley rats, i.e., when the epithelium is still developing. Growth factors or carrier solution (0.9\%NaCl with 0.25\%bovine serum albumin to prevent nonspecific binding) were applied (10 microliters) to the left nostril once per day starting shortly after birth on postnatal day 1 (P1), P2 and P3, and the animals were sacrificed on P4 by decapitation. After paraformaldehyde immersion fixation, cryostat sections of the olfactory area of the nose were immunostained for the proliferating cell nuclear antigen (PCNA). Sections were position-matched by turbinate structure and then epithelial height and area of PCNA staining at the base of the epithelium (which represents division of primarily neuronal precursors) were measured by image analysis. Both were significantly increased by rat IGF-1 (20 ng/ml, 2.6 nM), but not insulin (20 ng/ml, 2.6 nM) or an IGF-1 derivative, LongR3 IGF-1 (200 ng/ml, 22 nM), that does not bind to the IGF-1 binding proteins (IGFBPs). Thus IGF-1 appears to influence the rate of olfactory neurogenesis, and its actions are not modified by the IGFBPs. These data suggest an important role for IGF-1 in the OE.}, Author = {Pixley, S. K. and Dangoria, N. S. and Odoms, K. K. and Hastings, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Ann N Y Acad Sci}, Keywords = {Rats, Sprague-Dawley;C;Rats;Hypoglycemic Agents/pharmacology;Animal;Cattle;Insulin-Like Growth Factor I/*pharmacology;Olfactory Receptor Neurons/*cytology;Cells, Cultured;04 Adult neurogenesis factors;Insulin/pharmacology;Support, U.S. Gov't, P.H.S.;Cell Differentiation/drug effects}, Organization = {Department of Cell Biology, University of Cincinnati College of Medicine, Ohio 45267, USA. sarah.pixley\@uc.edu}, Pages = {244-7.}, Title = {Effects of insulin-like growth factor 1 on olfactory neurogenesis in vivo and in vitro}, Uuid = {43577B85-7A37-4437-B445-EC0F34A8C75E}, Volume = {855}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9929614}} @article{Pixley:1984, Abstract = {A monoclonal antibody to vimentin (RBA1) and a polyclonal antiserum to glial fibrillary acidic protein (GFAP) were used in double labeling experiments to examine astrocyte intermediate filaments in development and wounding. RBA1 bound to radial glia in newborn rat parietal cortex that are predominantly anti-GFAP-negative. The RBA1-positive radial fibers disappeared by postnatal day 20 with the greatest rate of disappearance occurring between day 8 and day 15. Between birth and day 20, the anti-GFAP staining increased to the adult pattern in mature shaped astrocytes. Some overlay was observed between the binding patterns of the two antibodies. Stab wounds to cortical areas were made at a developmental time when there were normally no RBA1-positive astrocytes. RBA1-positivity was present in some astrocytes but only at the edges of the wounds. The distribution patterns of RBA1-positive cells led to hypotheses concerning the possible function of vimentin in astrocytes and its regulation during development and wounding.}, Author = {Pixley, S. K. and de Vellis, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {10 Development;Glial Fibrillary Acidic Protein;Research Support, Non-U.S. Gov't;Rats;10 Hippocampus;Antibodies, Monoclonal;Research Support, U.S. Gov't, P.H.S.;Astrocytes;Cerebellum;Research Support, U.S. Gov't, Non-P.H.S.;Fluorescent Antibody Technique;Animals;Cerebral Cortex;Vimentin}, Medline = {85001403}, Month = {8}, Nlm_Id = {0045503}, Number = {2}, Pages = {201-9}, Pubmed = {6383523}, Title = {Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin}, Uuid = {64F46DA3-69C2-4CB3-AAAE-A0F52E774130}, Volume = {317}, Year = {1984}} @article{Pixley:1984a, Abstract = {A monoclonal antibody was developed using rat astrocytes purified in vitro as the starting antigenic material. Selection of the monoclonal was on the basis of astrocyte binding specificity in brain sections using indirect immunofluorescence techniques. The antibody (RBA2) that was chosen was specific for astrocytes in that it did not stain neurons or oligodendrocytes in frozen brain sections. It did, however, show binding to vascular smooth muscle and meningeal cells. The antigenic determinant(s) was determined to be on filaments of the intermediate-size class in cultured astrocytes and fibroblasts. From analysis of binding patterns in various tissues and in immunoblots, it was found that RBA2 cross-reacted strongly with glial fibrillary acidic protein (GFAP) and desmin. There was a weaker cross-reactivity to a vimentin-associated component. It is proposed that this antibody can be used as an astrocyte and blood vessel marker in brain sections, a vimentin marker in cultures and as a probe of intermediate filament composition and distribution.}, Author = {Pixley, S. K. and Kobayashi, Y. and de Vellis, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Glial Fibrillary Acidic Protein;10 Development;10 Hippocampus;Animals;Astrocytes;Cells, Cultured;Mice, Inbred BALB C;Rats;Fluorescent Antibody Technique;Comparative Study;Research Support, U.S. Gov't, Non-P.H.S.;Cross Reactions;Cell Line;Research Support, U.S. Gov't, P.H.S.;Antibody Specificity;Antibodies, Monoclonal;Intermediate Filament Proteins;Epitopes;Mice;Research Support, Non-U.S. Gov't}, Medline = {85083150}, Nlm_Id = {7600111}, Number = {4}, Pages = {525-41}, Pubmed = {6210375}, Title = {Monoclonal antibody to intermediate filament proteins in astrocytes}, Uuid = {B4E79C49-367A-409C-9220-4F414864F9C7}, Volume = {12}, Year = {1984}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.490120402}} @article{Pixley:1992, Abstract = {Olfactory receptor neurons (ORNs) are replaced and differentiate in adult animals, but differentiation in dissociated cell culture has not been demonstrated. To test whether contact with the CNS regulates maturation, neonatal rat olfactory cells were grown on a culture substrate or on CNS astrocytes. Mature ORNs, immunopositive for olfactory marker protein (OMP), disappeared rapidly from both systems. Neurons positive for neuron-specific tubulin (immature and mature) disappeared from substrate-only cultures, but remained abundant in the cocultures. OMP-positive neurons reappeared after 10 days in vitro. Pulse labeling with [3H]thymidine showed extensive neurogenesis of both immature and mature olfactory neurons. This demonstrates, in vitro, both division and differentiation of olfactory progenitor cells. eng Journal Article}, Author = {Pixley, S. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Journal = {Neuron}, Keywords = {Cell Differentiation;Stem Cells/cytology/*physiology;Neuroglia/cytology/*physiology;G abstr;Cytological Techniques;Cell Aging;Neurons/cytology/*physiology;Cell Survival;Cell Division;11 Glia;Animal;Support, U.S. Gov't, P.H.S.;Olfactory Bulb/*cytology;Cells, Cultured;Nasal Cavity/cytology;Support, Non-U.S. Gov't;Brain/*cytology}, Number = {6}, Organization = {Department of Anatomy and Cell Biology, University of Cincinnati College of Medicine, Ohio 45267-0521.}, Pages = {1191-204.}, Title = {CNS glial cells support in vitro survival, division, and differentiation of dissociated olfactory neuronal progenitor cells}, Uuid = {6AEC5568-F1D1-416C-92AE-E71A3822D17D}, Volume = {8}, Year = {1992}} @article{Pixley:1994, Abstract = {Production and differentiation of olfactory neurons occur in spherical, multi-neuronal aggregates that form in cultures where dissociated newborn rat nasal cells are plated on to CNS glial cells. We show here that neuronal cell bodies were primarily located in the peripheral layers of the spheres, and almost every neuronal sphere contained one or several non-cellular central cavities. The dendrite-like processes of the olfactory neurons, immunostained for neuron-specific tubulin or the olfactory marker protein, were aligned and directed towards the central cavities. Olfactory neurons in the intact animal show a similar relationship with the nasal lumen. Non-neuronal cells formed multiple layers centrally, bordering the cavities. This degree of phenotypic re-creation is unusual in a dissociated monolayer culture system. eng Journal Article}, Author = {Pixley, S. K. and Bage, M. and Miller, D. and Miller, M. L. and Shi, M. and Hastings, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Journal = {Neuroreport}, Keywords = {13 Olfactory bulb anatomy;Cell Differentiation;Cell Separation;Cells, Cultured;Epithelium/cytology;Rats;Neurons/*ultrastructure;Phenotype;Animal;Cell Movement;Astrocytes/physiology;Cell Communication;Cell Polarity;Rats, Sprague-Dawley;Nerve Tissue Proteins/analysis;Animals, Newborn;Brain/cytology;Support, U.S. Gov't, P.H.S.;Nasal Mucosa/*cytology;Biological Markers/analysis;I abstr}, Number = {5}, Organization = {Department of Anatomy and Cell Biology, University of Cincinnati Medical College, OH 45267-0521.}, Pages = {543-8.}, Title = {Olfactory neurons in vitro show phenotypic orientation in epithelial spheres}, Uuid = {7648665C-EF2A-49AF-B097-A675C8F0C563}, Volume = {5}, Year = {1994}} @article{Pizzorusso:2002, Abstract = {In young animals, monocular deprivation leads to an ocular dominance shift, whereas in adults after the critical period there is no such shift. Chondroitin sulphate proteoglycans (CSPGs) are components of the extracellular matrix (ECM) inhibitory for axonal sprouting. We tested whether the developmental maturation of the ECM is inhibitory for experience-dependent plasticity in the visual cortex. The organization of CSPGs into perineuronal nets coincided with the end of the critical period and was delayed by dark rearing. After CSPG degradation with chondroitinase-ABC in adult rats, monocular deprivation caused an ocular dominance shift toward the nondeprived eye. The mature ECM is thus inhibitory for experience-dependent plasticity, and degradation of CSPGs reactivates cortical plasticity. 1095-9203 Journal Article}, Author = {Pizzorusso, T. and Medini, P. and Berardi, N. and Chierzi, S. and Fawcett, J. W. and Maffei, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Science}, Keywords = {Extracellular Matrix/*metabolism;Animals;Axons/physiology;*Neuronal Plasticity;Rats;Proteochondroitin Sulfates/*metabolism;*Dominance, Ocular;Visual Cortex/*physiology;Darkness;Synapses/physiology;11 Glia;Time Factors;Support, Non-U.S. Gov't;Extracellular Matrix Proteins/metabolism;Chondroitin ABC Lyase/*metabolism;Light;Nerve Tissue Proteins/metabolism;G pdf;Visual Acuity;Neurons/physiology;Glycosaminoglycans/metabolism}, Number = {5596}, Organization = {Scuola Normale Superiore, 56100 Pisa, Italy. tommaso\@in.pi.cnr.it}, Pages = {1248-51}, Title = {Reactivation of ocular dominance plasticity in the adult visual cortex}, Uuid = {7BF008FC-F6AC-4F07-A18F-087722765B26}, Volume = {298}, Year = {2002}, url = {papers/Pizzorusso_Science2002.pdf}} @article{Plas:2005, Abstract = {The map of the retina onto the optic tectum is a highly conserved feature of the vertebrate visual system; the mechanism by which this mapping is accomplished during development is a long-standing problem of neurobiology. The early suggestion by Roger Sperry that the map is formed through interactions between retinal ganglion cell axons and target cells within the tectum has gained significant experimental support and widespread acceptance. Nonetheless, reports in a variety of species indicate that some aspects of retinotopic order exist within the optic tract, leading to the suggestion that this "preordering" of retinal axons may play a role in the formation of the mature tectal map. A satisfactory account of pretarget order must provide the mechanism by which such axon order develops. Insofar as this mechanism must ultimately be determined genetically, the mouse suggests itself as the natural species in which to pursue these studies. Quantitative and repeatable methods are required to assess the contribution of candidate genes in mouse models. For these reasons, we have undertaken a quantitative study of the degree of retinotopic order within the optic tract and nerve of wild-type mice both before and after the development of the retinotectal map. Our methods are based on tract tracing using lipophilic dyes, and our results indicate that there is a reestablishment of dorsoventral but not nasotemporal retinal order when the axons pass through the chiasm and that this order is maintained throughout the subsequent tract. Furthermore, this dorsoventral retinotopic order is well established by the day after birth, long before the final target zone is discernible within the tectum. We conclude that pretarget sorting of axons according to origin along the dorsoventral axis of the retina is both spatially and chronologically appropriate to contribute to the formation of the retinotectal map, and we suggest that these methods be used to search for the molecular basis of such order by using available mouse genetic models.}, Author = {Plas, Daniel T. and Lopez, Joshua E. and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Imaging, Three-Dimensional;Retina;24 Pubmed search results 2008;research support, non-u.s. gov't;Mice, Inbred C57BL;research support, n.i.h., extramural;Animals, Newborn;Optic Nerve;Animals;Mice;Superior Colliculi;Visual Pathways;Axons; 21 Activity-development}, Month = {10}, Nlm_Id = {0406041}, Number = {4}, Organization = {Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.}, Pages = {305-19}, Pubmed = {16175549}, Title = {Pretarget sorting of retinocollicular axons in the mouse}, Uuid = {5BD892C6-7A62-4019-8DF9-39B3ECC10F0E}, Volume = {491}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20694}} @article{Plas:2008, Abstract = {Patterning events during early eye formation determine retinal cell fate and can dictate the behavior of retinal ganglion cell (RGC) axons as they navigate toward central brain targets. The temporally and spatially regulated expression of bone morphogenetic proteins (BMPs) and their receptors in the retina are thought to play a key role in this process, initiating gene expression cascades that distinguish different regions of the retina, particularly along the dorsoventral axis. Here, we examine the role of BMP and a potential downstream effector, EphB, in retinotopic map formation in the lateral geniculate nucleus (LGN) and superior colliculus (SC). RGC axon behaviors during retinotopic map formation in wild-type mice are compared with those in several strains of mice with engineered defects of BMP and EphB signaling. Normal RGC axon sorting produces axon order in the optic tract that reflects the dorsoventral position of the parent RGCs in the eye. A dramatic consequence of disrupting BMP signaling is a missorting of RGC axons as they exit the optic chiasm. This sorting is not dependent on EphB. When BMP signaling in the developing eye is genetically modified, RGC order in the optic tract and targeting in the LGN and SC are correspondingly disrupted. These experiments show that BMP signaling regulates dorsoventral RGC cell fate, RGC axon behavior in the ascending optic tract, and retinotopic map formation in the LGN and SC through mechanisms that are in part distinct from EphB signaling in the LGN and SC.}, Author = {Plas, Daniel T. and Dhande, Onkar S. and Lopez, Joshua E. and Murali, Deepa and Thaller, Christina and Henkemeyer, Mark and Furuta, Yasuhide and Overbeek, Paul and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Retina;Animals;Xenopus;Humans;Carrier Proteins;Transforming Growth Factor beta;Superior Colliculi;Visual Pathways;Mutation;Mice, Transgenic;Bone Morphogenetic Proteins;Bone Morphogenetic Protein Receptors, Type I;Eye;Animals, Newborn;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;in vitro; 21 Activity-development}, Month = {7}, Nlm_Id = {8102140}, Number = {28}, Organization = {Department of Neuroscience, University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.}, Pages = {7057-67}, Pii = {28/28/7057}, Pubmed = {18614674}, Title = {Bone morphogenetic proteins, eye patterning, and retinocollicular map formation in the mouse}, Uuid = {F35C53A6-9DF7-4888-B180-3DE7A4DFD903}, Volume = {28}, Year = {2008}, url = {papers/Plas_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3598-06.2008}} @article{Pleasure:2000, Abstract = {The dentate gyrus of the hippocampus is uniquely organized with a displaced proliferative zone that continues to generate dentate granule cells throughout life. We have analyzed the expression of Notch receptors, Notch ligands, and basic helix-loop-helix (bHLH) genes during dentate gyrus development to determine whether the need to maintain a pool of undifferentiated precursors is reflected in the patterns of expression of these genes. Many of these genes are expressed diffusely throughout the cortical neuroepithelium at embryonic days 16 and 17 in the rat, just preceding the migration of newly born granule cells and dentate precursor cells into the dentate anlage. However, at this time, Mash1, Math3, and Id3 expression are all concentrated in the area that specifically gives rise to granule cells and dentate precursor cells. Two days later, at the time of migration of the first granule cells and dentate precursor cells, cells expressing Mash1 are seen in the migratory route from the subventricular zone to the developing dentate gyrus. Newly born granule cells expressing NeuroD are also present in this migratory pathway. In the first postnatal week, precursor cells expressing Mash1 reside in the dentate hilus, and by the third postnatal week they have largely taken up their final position in the subgranular zone along the hilar side of the dentate granule cell layer. After terminal differentiation, granule cells born in the hilus or the subgranular zone begin to express NeuroD followed by NeuroD2. This study establishes that the expression patterns of bHLH mRNAs evolve during the formation of the dentate gyrus, and the precursor cells resident in the mature dentate gyrus share features with precursor cells found in development. Thus, many of the same mechanisms that are known to regulate cell fate and precursor pool size in other brain regions are likely to be operative in the dentate gyrus at all stages of development.}, Author = {Pleasure, S. J. and Collins, A. E. and Lowenstein, D. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Pregnancy;Cell Differentiation;Animals;Transcription Factors;DNA-Binding Proteins;Gene Expression Regulation, Developmental;Rats;Female;Cell Movement;Rats, Sprague-Dawley;Embryo;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neurons;Dentate Gyrus;Membrane Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {20394094}, Month = {8}, Nlm_Id = {8102140}, Number = {16}, Organization = {Department of Neurology, Epilepsy Research Laboratory, University of California, San Francisco, California 94143, USA.}, Pages = {6095-105}, Pii = {20/16/6095}, Pubmed = {10934259}, Title = {Unique expression patterns of cell fate molecules delineate sequential stages of dentate gyrus development}, Uuid = {AD8B0A18-A3E5-11DA-AB00-000D9346EC2A}, Volume = {20}, Year = {2000}, url = {papers/Pleasure_JNeurosci2000.pdf}} @article{Plenz:2007, Abstract = {Neuronal avalanches are spatiotemporal patterns of neuronal activity that occur spontaneously in superficial layers of the mammalian cortex under various experimental conditions. These patterns reflect fast propagation of local synchrony, display a rich spatiotemporal diversity and recur over several hours. The statistical organization of pattern sizes is invariant to the choice of spatial scale, demonstrating that the functional linking of cortical sites into avalanches occurs on all spatial scales with a fractal organization. These features suggest an underlying network of neuronal interactions that balances diverse representations with predictable recurrence, similar to what has been theorized for cell assembly formation. We propose that avalanches reflect the transient formation of cell assemblies in the cortex and discuss various models that provide mechanistic insights into the underlying dynamics, suggesting that they arise in a critical regime.}, Author = {Plenz, Dietmar and Thiagarajan, Tara C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Neurons;Cell Communication;Models, Neurological;Neural Pathways;Signal Transduction;research support, n.i.h., intramural;Cortical Synchronization;Animals;Humans;24 Pubmed search results 2008;Cerebral Cortex;review}, Month = {3}, Nlm_Id = {7808616}, Number = {3}, Organization = {Section of Neural Network Physiology, National Institute of Mental Health, Porter Neuroscience Research Center, 35 Convent Drive, Bethesda, MD 20892, USA. plenzd\@mail.nih.gov}, Pages = {101-10}, Pii = {S0166-2236(07)00019-7}, Pubmed = {17275102}, Title = {The organizing principles of neuronal avalanches: cell assemblies in the cortex?}, Uuid = {C21A329B-7EC4-4EA2-A9D8-E3643FF04AA7}, Volume = {30}, Year = {2007}, url = {papers/Plenz_TrendsNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2007.01.005}} @article{Pluchino:2003, Abstract = {Widespread demyelination and axonal loss are the pathological hallmarks of multiple sclerosis. The multifocal nature of this chronic inflammatory disease of the central nervous system complicates cellular therapy and puts emphasis on both the donor cell origin and the route of cell transplantation. We established syngenic adult neural stem cell cultures and injected them into an animal model of multiple sclerosis--experimental autoimmune encephalomyelitis (EAE) in the mouse--either intravenously or intracerebroventricularly. In both cases, significant numbers of donor cells entered into demyelinating areas of the central nervous system and differentiated into mature brain cells. Within these areas, oligodendrocyte progenitors markedly increased, with many of them being of donor origin and actively remyelinating axons. Furthermore, a significant reduction of astrogliosis and a marked decrease in the extent of demyelination and axonal loss were observed in transplanted animals. The functional impairment caused by EAE was almost abolished in transplanted mice, both clinically and neurophysiologically. Thus, adult neural precursor cells promote multifocal remyelination and functional recovery after intravenous or intrathecal injection in a chronic model of multiple sclerosis. 0028-0836 Journal Article}, Author = {Pluchino, S. and Quattrini, A. and Brambilla, E. and Gritti, A. and Salani, G. and Dina, G. and Galli, R. and Del Carro, U. and Amadio, S. and Bergami, A. and Furlan, R. and Comi, G. and Vescovi, A. L. and Martino, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:56 -0400}, Journal = {Nature}, Keywords = {Cell Differentiation;Animals;Disease Progression;Encephalomyelitis, Experimental;Brain Tissue Transplantation;*Stem Cell Transplantation;L pdf;Cell Movement;Cell Count;Stem Cells/cytology;Aging/*physiology;Chronic Disease;17 Transplant Regeneration;Injections, Intraventricular;Oligodendroglia/cytology/pathology;Support, Non-U.S. Gov't;Autoimmune/metabolism/pathology/physiopathology/therapy;Nerve Fibers, Myelinated/metabolism/pathology;RNA, Messenger/genetics/metabolism;Mice;Injections, Intravenous;Neurons/*cytology/metabolism/pathology/*transplantation;*Tissue Therapy;Axons/metabolism/pathology;Multiple Sclerosis/metabolism/*pathology/physiopathology/*therapy;Growth Substances/genetics}, Number = {6933}, Organization = {Neuroimmunology Unit-DIBIT, San Raffaele Hospital, via Olgettina 58, 20132 Milano, Italy.}, Pages = {688-94}, Title = {Injection of adult neurospheres induces recovery in a chronic model of multiple sclerosis}, Uuid = {8A098DB8-2922-4919-8B5A-60035F7C5770}, Volume = {422}, Year = {2003}, url = {papers/Pluchino_Nature2003.pdf}} @article{Pluchino:2005, Abstract = {In degenerative disorders of the central nervous system (CNS), transplantation of neural multipotent (stem) precursor cells (NPCs) is aimed at replacing damaged neural cells. Here we show that in CNS inflammation, NPCs are able to promote neuroprotection by maintaining undifferentiated features and exerting unexpected immune-like functions. In a mouse model of chronic CNS inflammation, systemically injected adult syngeneic NPCs use constitutively activated integrins and functional chemokine receptors to selectively enter the inflamed CNS. These undifferentiated cells survive repeated episodes of CNS inflammation by accumulating within perivascular areas where reactive astrocytes, inflamed endothelial cells and encephalitogenic T cells produce neurogenic and gliogenic regulators. In perivascular CNS areas, surviving adult NPCs induce apoptosis of blood-borne CNS-infiltrating encephalitogenic T cells, thus protecting against chronic neural tissue loss as well as disease-related disability. These results indicate that undifferentiated adult NPCs have relevant therapeutic potential in chronic inflammatory CNS disorders because they display immune-like functions that promote long-lasting neuroprotection.}, Author = {Pluchino, Stefano and Zanotti, Lucia and Rossi, Barbara and Brambilla, Elena and Ottoboni, Linda and Salani, Giuliana and Martinello, Marianna and Cattalini, Alessandro and Bergami, Alessandra and Furlan, Roberto and Comi, Giancarlo and Constantin, Gabriela and Martino, Gianvito}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {T-Lymphocytes;Cell Differentiation;Animals;Stem Cell Transplantation;Brain Tissue Transplantation;Multipotent Stem Cells;Chemotaxis;Neuroprotective Agents;Apoptosis;11 Glia;Chronic Disease;17 Transplant Regeneration;Disease Models, Animal;Microspheres;Cell Adhesion;Encephalomyelitis, Autoimmune, Experimental;Receptors, Chemokine;Integrin alpha4beta1;Mice;24 Pubmed search results 2008;Central Nervous System;Inflammation;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {0410462}, Number = {7048}, Organization = {Neuroimmunology Unit-DIBIT, Vita-Salute University, San Raffaele Hospital, via Olgettina 58, 20132 Milan, Italy.}, Pages = {266-71}, Pii = {nature03889}, Pubmed = {16015332}, Title = {Neurosphere-derived multipotent precursors promote neuroprotection by an immunomodulatory mechanism}, Uuid = {93B44DD9-F510-4A37-9A7E-5460339A2031}, Volume = {436}, Year = {2005}, url = {papers/Pluchino_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03889}} @article{Plumpe:2006, Abstract = {BACKGROUND: In the course of adult hippocampal neurogenesis most regulation takes place during the phase of doublecortin (DCX) expression, either as pro-proliferative effect on precursor cells or as survival-promoting effect on postmitotic cells. We here obtained quantitative data about the proliferative population and the dynamics of postmitotic dendrite development during the period of DCX expression. The question was, whether any indication could be obtained that the initiation of dendrite development is timely bound to the exit from the cell cycle. Alternatively, the temporal course of morphological maturation might be subject to additional regulatory events. RESULTS: We found that (1) 20\%of the DCX population were precursor cells in cell cycle, whereas more than 70\%were postmitotic, (2) the time span until newborn cells had reached the most mature stage associated with DCX expression varied between 3 days and several weeks, (3) positive or negative regulation of precursor cell proliferation did not alter the pattern and dynamics of dendrite development. Dendrite maturation was largely independent of close contacts to astrocytes. CONCLUSION: These data imply that dendrite maturation of immature neurons is initiated at varying times after cell cycle exit, is variable in duration, and is controlled independently of the regulation of precursor cell proliferation. We conclude that in addition to the major regulatory events in cell proliferation and selective survival, additional micro-regulatory events influence the course of adult hippocampal neurogenesis.}, Author = {Pl{\"u}mpe, Tobias and Ehninger, Dan and Steiner, Barbara and Klempin, Friederike and Jessberger, Sebastian and Brandt, Moritz and R{\"o}mer, Benedikt and Rodriguez, Gerardo Ramirez and Kronenberg, Golo and Kempermann, Gerd}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1471-2202}, Journal = {BMC Neurosci}, Keywords = {Cell Survival;Microtubule-Associated Proteins;Animals;Astrocytes;Seizures;comparative study;Physical Conditioning, Animal;Female;Cell Count;Mice, Transgenic;Hippocampus;Mice, Inbred C57BL;Kainic Acid;research support, non-u.s. gov't;Behavior, Animal;Cell Proliferation;Dendrites;Neuropeptides;In Situ Nick-End Labeling;Blotting, Western;Neurons;Organogenesis;Age Factors;Maze Learning;Mice;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine}, Nlm_Id = {100966986}, Organization = {Max Delbr{\"u}ck Center for Molecular Medicine (MDC) Berlin-Buch, Germany. biotobi\@gmx.net }, Pages = {77}, Pii = {1471-2202-7-77}, Pubmed = {17105671}, Title = {Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation}, Uuid = {C272549E-5DD7-4AED-A5CD-9EC43D453504}, Volume = {7}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1471-2202-7-77}} @article{Pogosian:1971, Author = {Pogosian, V. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0004-1947}, Journal = {Arkh Anat Gistol Embriol}, Keywords = {Axons;Dendrites;Dogs;Animals;24 Pubmed search results 2008;Neurons;Frontal Lobe}, Medline = {72167811}, Month = {9}, Nlm_Id = {0370603}, Number = {9}, Pages = {32-9}, Pubmed = {5147139}, Title = {[Neuronal thorns in the frontal cortex of the dog]}, Uuid = {C896C208-A421-4334-805F-880AADC1760A}, Volume = {61}, Year = {1971}} @article{Polack:2007, Abstract = {Typical absence has long been considered as the prototypic form of generalized nonconvulsive epileptic seizures. Recent investigations in patients and animal models suggest that absence seizures could originate from restricted regions of the cerebral cortex. However, the cellular and local network processes of seizure initiation remain unknown. Here, we show that absence seizures in Genetic Absence Epilepsy Rats from Strasbourg, a well established genetic model of this disease, arise from the facial somatosensory cortex. Using in vivo intracellular recordings, we found that epileptic discharges are initiated in layer 5/6 neurons of this cortical region. These neurons, which show a distinctive hyperactivity associated with a membrane depolarization, lead the firing of distant cortical cells during the epileptic discharge. Consistent with their ictogenic properties, neurons from this "focus" exhibit interictal and preictal oscillations that are converted into epileptic pattern. These results confirm and extend the "focal hypothesis" of absence epilepsy and provide a cellular scenario for the initiation and generalization of absence seizures.}, Author = {Polack, Pierre-Olivier O. and Guillemain, Isabelle and Hu, Emilie and Deransart, Colin and Depaulis, Antoine and Charpier, St{\'e}phane}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;Epilepsy, Absence;Action Potentials;Rats;Analysis of Variance;Wakefulness;Rats, Wistar;Face;Biotin;Brain Mapping;Models, Genetic;Animals;Periodicity;Somatosensory Cortex;Neurons;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {8102140}, Number = {24}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale Unit{\'e} 667, Coll\`{e}ge de France, 75231 Paris, Cedex 05, France. pierre-olivier.polack\@college-de-france.fr}, Pages = {6590-9}, Pii = {27/24/6590}, Pubmed = {17567820}, Title = {Deep layer somatosensory cortical neurons initiate spike-and-wave discharges in a genetic model of absence seizures}, Uuid = {9BFDF282-FFCB-4C7C-9FA8-1012B47F4A8C}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0753-07.2007}} @article{Poleshchuk:1988, Abstract = {Ultrastructural changes, various by their character and the degree of expression, have been found in axons of the spinal cord of guinea-pigs with amyotrophic leukospongiosis (AL) (a slow infection of the CNS). The dependence of the degree of degenerative changes on the disease duration is shown. Absorption of cellular debris by oligodendrocytes and astrocytes is noted. It seems that microglia does not participate in phagocytosis. The conclusion has been made that experimental AL is a convenient model for studying the mechanisms of death of the central axons and analysis of the glia cell function under the conditions of keeping the blood-brain barrier intact.}, Author = {Poleshchuk, N. N. and Votiakov, V. I. and Shalapenok, L. S. and Kolomiets, N. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0365-9615}, Journal = {Biull Eksp Biol Med}, Keywords = {Spinal Cord Diseases;Nerve Degeneration;Blood-Brain Barrier;Comparative Study;Microscopy, Electron;Guinea Pigs;English Abstract;Not relevant;Time Factors;11 Glia;Spinal Cord;Animals;Slow Virus Diseases;Axons}, Medline = {89088498}, Month = {12}, Nlm_Id = {0370627}, Number = {12}, Pages = {734-7}, Pubmed = {3207884}, Title = {[Ultrastructural changes in the axons of the central nervous system in experimental amyotrophic leukospongiosis]}, Uuid = {FC30437D-F5B2-4CED-AD28-87EA000D2C9B}, Volume = {106}, Year = {1988}} @article{Pollard:2003, Abstract = {Eukaryotic cells depend on cytoskeletal polymers and molecular motors to establish their asymmetrical shapes, to transport intracellular constituents and to drive their motility. Cell biologists are using diverse experimental approaches to understand the molecular basis of cellular movements and to explain why defects in the component proteins cause disease. Much of the molecular machinery for motility evolved in early eukaryotes, so a limited set of general principles can explain the motility of most cells. 0028-0836 Comment Journal Article}, Author = {Pollard, T. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Nature}, Keywords = {Models, Biological;*Cell Movement;10 Development;Biopolymers/metabolism;Gene Deletion;Molecular Motors/metabolism;Eukaryotic Cells/cytology/metabolism;Pseudopodia/metabolism;Evolution;Animals;F pdf;Actins/metabolism;Cytoskeleton/*metabolism}, Number = {6933}, Organization = {Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven Connecticut 06520-8103, USA. thomas.pollard\@yale.edu}, Pages = {741-5}, Pubmed = {12700767}, Title = {The cytoskeleton, cellular motility and the reductionist agenda}, Uuid = {A7E87AB0-9055-46DE-B5E5-1FAAF3613887}, Volume = {422}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12700767}} @article{Polleux:2002, Abstract = {During telencephalic development, cells from the medial ganglionic eminence (MGE) are thought to migrate to the neocortex to give rise to a majority of cortical GABAergic interneurons. By combining time-lapse video-microscopy, immunofluorescence and pharmacological perturbations in a new in vitro migration assay, we find that MGE-derived cells migrate through the entire extent of the cortex and into the CA fields of the hippocampus, but avoid the dentate gyrus. Migrating neurons initially travel within the marginal zone and intermediate zone, and can enter the cortical plate from either location. Tangential migration is strongly stimulated by BDNF and NT4 and attenuated by the Trk-family inhibitor, K252a, suggesting that migration is regulated by TrkB signaling. Furthermore, TrkB-null mice show a significant decrease in the number of calbindin-positive neurons migrating tangentially in the embryonic cortex. BDNF and NT4 cause rapid activation of PI3-kinase in MGE cells, and inhibition of PI3-kinase (but not of MAP kinase or PLCgamma) dramatically attenuates tangential migration. These observations suggest that TrkB signaling, via PI3-kinase activation, plays an important role in controlling interneuron migration in the developing cerebral cortex.}, Author = {Polleux, Franck and Whitford, Kristin L. and Dijkhuizen, Paul A. and Vitalis, Tania and Ghosh, Anirvan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Research Support, Non-U.S. Gov't;Signal Transduction;Animals;Cells, Cultured;Coculture Techniques;Mice, Mutant Strains;Enzyme Inhibitors;Brain-Derived Neurotrophic Factor;Female;Cell Movement;Chromones;Phospholipase C;Green Fluorescent Proteins;Ganglia, Sensory;Morpholines;1-Phosphatidylinositol 3-Kinase;Nerve Growth Factors;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neurons;Receptor, trkB;Cell Transplantation;Mice;Carbazoles;24 Pubmed search results 2008;Luminescent Proteins;Isoenzymes;Phospholipase C gamma}, Medline = {22065264}, Month = {7}, Nlm_Id = {8701744}, Number = {13}, Organization = {INSERM U.371, 18 avenue Doyen L{\'e}pine, 69675 Bron, France.}, Pages = {3147-60}, Pubmed = {12070090}, Title = {Control of cortical interneuron migration by neurotrophins and PI3-kinase signaling}, Uuid = {1EE8D059-D248-42B1-A584-787BBD6EFBC0}, Volume = {129}, Year = {2002}} @article{Polleux:1997, Abstract = {Cortical neurons are generated in the germinal zones lining the ventricles before migrating predominantly radially. To investigate regional differences in the cell-cycle kinetics of neuroblasts, pulse [3H]-thymidine injections were made throughout corticogenesis, and labeled neuron counts were compared in areas 3, 6, 17, and 18a in the adult mouse. The relationship between height in the cortex and intensity of autoradiographic signal distinguishes first generation and subsequent generations of neurons. This provides the mitotic history of defined sets of neurons and is a powerful tool for analyzing areal differences in cell-cycle kinetics. The infragranular laminar labeling indices of different generations show significant differences in areas 3 and 6. The labeling index of first generation neurons shows that the rate of neuron production is higher in area 3 than in area 6. This increased generation rate in area 3 was accompanied by two major changes. First, computation of the labeling index of the subsequent generation neurons (which reflects percentages of precursors in S-phase at the moment of the pulse) indicates a shorter cell cycle in area 3. Second, the total population of labeled neurons contains a higher proportion of first generation neurons in area 3, implying a higher leaving fraction in this area. Computer simulations of these areal differences of cell-cycle kinetics generate neuron numbers that are in close agreement with published data. Altogether these findings reveal an early regionalization of the ventricular zone that serves to generate unique features of future cortical areas.}, Author = {Polleux, F. and Dehay, C. and Moraillon, B. and Kennedy, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Aging;Embryo;Mice, Inbred BALB C;Research Support, Non-U.S. Gov't;Thymidine;Embryonic and Fetal Development;Autoradiography;Models, Neurological;Time Factors;Cell Division;Computer Simulation;Cell Cycle;Animals;Mice;24 Pubmed search results 2008;Cerebral Cortex;Neurons}, Medline = {97461622}, Month = {10}, Nlm_Id = {8102140}, Number = {20}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U371-Cerveau et Vision, 69675 BRON Cedex, France.}, Pages = {7763-83}, Pubmed = {9315898}, Title = {Regulation of neuroblast cell-cycle kinetics plays a crucial role in the generation of unique features of neocortical areas}, Uuid = {86EC54A8-480D-4ADC-85C4-E6647CE319E2}, Volume = {17}, Year = {1997}} @article{Polleux:1998, Abstract = {In the homozygous (but not the heterozygous) reeler mutant, disruption of neuron migration leads to a major perturbation of the cortical environment that in turn could modify (1) the specification of neuronal fate and (2) the proliferation dynamics of cortical precursors. To investigate these issues, tritiated thymidine injections during cortical neurogenesis were coupled with postnatal injections of a retrograde tracer in the spinal cord to accurately measure the neurogenesis of corticospinal neurons in the heterozygous and homozygous mutant. The homozygous reeler shows (1) strict conservation of area-specific timetables of corticospinal neuron generation; (2) neurons with the appropriate birthdates show an enhanced probability of projecting to the spinal cord; (3) during early stages of corticogenesis, there is a reduced rate of neuron production followed at later stages by an increased rate of neuron production; and (4) these changes in the rate of neuron production were shown to be at least partially attributable to changes in the proportions of differentiative divisions. Taken together, our results show that in the developing cortex, the neurogenesis and specification of a given neuronal phenotype are partially controlled by the postmigratory compartment. On the other hand, neither areal identity nor the chronology of production of layer-specific neuronal phenotype seems to depend on the integrity of the cellular environment.}, Author = {Polleux, F. and Dehay, C. and Kennedy, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Mice, Inbred BALB C;Animals;Afferent Pathways;Neocortex;Thymidine;Female;Cell Count;Mice, Neurologic Mutants;Pyramidal Tracts;Male;Animals, Newborn;Neurons;Somatosensory Cortex;Mice;Cell Division;Tritium;24 Pubmed search results 2008;Cell Death;Research Support, Non-U.S. Gov't}, Medline = {99042065}, Month = {12}, Nlm_Id = {8102140}, Number = {23}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U371-Cerveau et Vision, 69675 Bron Cedex, France.}, Pages = {9910-23}, Pubmed = {9822747}, Title = {Neurogenesis and commitment of corticospinal neurons in reeler}, Uuid = {F08E8D57-B5AD-4737-AE13-CA9B4DC6524E}, Volume = {18}, Year = {1998}} @article{Polleux:2004, Abstract = {Autism is a complex, behaviorally defined, developmental brain disorder with an estimated prevalence of 1 in 1,000. It is now clear that autism is not a disease, but a syndrome with a strong genetic component. The etiology of autism is poorly defined both at the cellular and the molecular levels. Based on the fact that seizure activity is frequently associated with autism and that abnormal evoked potentials have been observed in autistic individuals in response to tasks that require attention, several investigators have recently proposed that autism might be caused by an imbalance between excitation and inhibition in key neural systems including the cortex. Despite considerable ongoing effort toward the identification of chromosome regions affected in autism and the characterization of many potential gene candidates, only a few genes have been reproducibly shown to display specific mutations that segregate with autism, likely because of the complex polygenic nature of this syndrome. Among those, several candidate genes have been shown to control the early patterning and/or the late synaptic maturation of specific neuronal subpopulations controlling the balance between excitation and inhibition in the developing cortex and cerebellum. In the present article, we review our current understanding of the developmental mechanisms patterning the balance between excitation and inhibition in the context of the neurobiology of autism.}, Author = {Polleux, Franck and Lauder, Jean M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1080-4013}, Journal = {Ment Retard Dev Disabil Res Rev}, Keywords = {Research Support, Non-U.S. Gov't;gamma-Aminobutyric Acid;Magnetic Resonance Imaging;Chromosomes, Human, Pair 16;Humans;Glutamic Acid;Chromosomes, Human, Pair 17;Brain;review;Chromosomes, Human, Pair 19;Research Support, U.S. Gov't, P.H.S.;Chromosomes, Human, Pair 20;Autistic Disorder;Cerebellum;24 Pubmed search results 2008;Brain Stem;Gene Expression;Chromosomes, Human, Pair 15;Genetic Markers}, Nlm_Id = {9517974}, Number = {4}, Organization = {Department of Pharmacology-Neuroscience Center, School of Medicine, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA. polleux\@med.unc.edu}, Pages = {303-17}, Pubmed = {15666334}, Title = {Toward a developmental neurobiology of autism}, Uuid = {F7462B60-170B-420C-AA2C-597E95FA9740}, Volume = {10}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/mrdd.20044}} @article{Polleux:2000, Abstract = {The apical dendrites of pyramidal neurons integrate inputs from various cortical layers and are central to information processing. Here we show that the growth of apical dendrites towards the pial surface is regulated by a diffusible chemoattractant present at high levels near the marginal zone. A major component of this signal is semaphorin 3A (Sema3A), which was previously characterized as a chemorepellant for cortical axons. Soluble guanylate cyclase is asymmetrically localized to the developing apical dendrite, and is required for the chemoattractive effect of Sema3A. Thus the asymmetric localization of soluble guanylate cyclase confers distinct Sema3A responses to axons and dendrites. These observations reveal a mechanism by which a single chemotropic signal can pattern both axons and dendrites during development.}, Author = {Polleux, F. and Morrow, T. and Ghosh, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Glycoproteins;Signal Transduction;Animals;Cells, Cultured;Coculture Techniques;Rats;Solubility;Receptors, Cell Surface;Protein Kinases;Axons;Mice, Transgenic;Pyramidal Cells;Neuropilin-1;Green Fluorescent Proteins;Nerve Growth Factors;Cyclic GMP-Dependent Protein Kinases;Dendrites;Research Support, U.S. Gov't, P.H.S.;Guanylate Cyclase;Cerebral Cortex;Mice;Semaphorin-3A;24 Pubmed search results 2008;Chemotactic Factors;Luminescent Proteins;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {20227299}, Month = {4}, Nlm_Id = {0410462}, Number = {6778}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, USA.}, Pages = {567-73}, Pubmed = {10766232}, Title = {Semaphorin 3A is a chemoattractant for cortical apical dendrites}, Uuid = {2B7F83DF-1A4D-4864-8227-610D7B166616}, Volume = {404}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35007001}} @article{Polleux:2005, Abstract = {Great neuroanatomists of the twentieth century recognized that the cerebral cortex of mammals is the single most complex structure of the central nervous system both in terms of neuronal diversity and connectivity. Understanding the cellular and molecular mechanisms specifying the afferent and efferent connectivity in the neocortex may seem like a daunting task. However, recent technical advances have greatly improved our ability to (1) profile gene expression of neuronal populations isolated based on their connectional properties, (2) manipulate gene expression in specific neuronal populations, and (3) visualize their axonal projections in vivo. These new tools are revolutionizing our ability to identify the molecular mechanisms patterning afferent and efferent cortical projections.}, Author = {Polleux, Franck}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {University of North Carolina, Neuroscience Center, Deptartment of Pharmacology, 105 Mason Farm Road-CB7250, Chapel Hill, North Carolina 27599, USA. polleux\@med.unc.edu}, Pages = {395-400}, Pii = {S0896-6273(05)00353-3}, Pubmed = {15882638}, Title = {Genetic mechanisms specifying cortical connectivity: let's make some projections together}, Uuid = {B59F74D1-5E56-4CC1-AAF3-F3D1FE8A7895}, Volume = {46}, Year = {2005}, url = {papers/Polleux_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.017}} @article{Polleux:1998a, Abstract = {Cortical neurons communicate with various cortical and subcortical targets by way of stereotyped axon projections through the white matter. Slice overlay experiments indicate that the initial growth of cortical axons toward the white matter is regulated by a diffusible chemorepulsive signal localized near the marginal zone. Semaphorin III is a major component of this diffusible signal, and cortical neurons transduce this signal by way of the neuropilin-1 receptor. These observations indicate that semaphorin-neuropilin interactions play a critical role in the initial patterning of projections in the developing cortex.}, Author = {Polleux, F. and Giger, R. J. and Ginty, D. D. and Kolodkin, A. L. and Ghosh, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Glycoproteins;Signal Transduction;Animals;Gene Targeting;In Vitro;Coculture Techniques;Rats;Humans;Neurons, Efferent;Recombinant Proteins;Axons;Neuropilin-1;Nerve Growth Factors;Cell Line;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Mice;Semaphorin-3A;24 Pubmed search results 2008;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {99055402}, Month = {12}, Nlm_Id = {0404511}, Number = {5395}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.}, Pages = {1904-6}, Pubmed = {9836643}, Title = {Patterning of cortical efferent projections by semaphorin-neuropilin interactions}, Uuid = {7B48C1C2-BCC3-48D6-B9DC-B16C5ACF2A4B}, Volume = {282}, Year = {1998}} @article{Polo:2006, Abstract = {Endocytosis is used by eukaryotic cells to regulate nutrient internalization, signal transduction, and the composition of the plasma membrane. However, a more complex picture is emerging, in which endocytic pathways integrate diverse signals, thereby contributing to a higher level of cellular and organismal organization. In this way, endocytosis and cell signaling are intertwined in many biological processes, such as cell motility and cell fate determination.}, Author = {Polo, Simona and Di Fiore, Pier Paolo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {0413066}, Number = {5}, Organization = {IFOM, Istituto FIRC di Oncologia Molecolare, Via Adamello 16, 20134 Milan, Italy. simona.polo\@ifom-ieo-campus.it}, Pages = {897-900}, Pii = {S0092-8674(06)00242-X}, Pubmed = {16530038}, Title = {Endocytosis conducts the cell signaling orchestra}, Uuid = {62D36A7A-1789-4F29-AD83-97EBE141F30E}, Volume = {124}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.02.025}} @article{Polo-Parada:2001, Abstract = {Although functional neuromuscular junctions (NMJs) form in NCAM-deficient mice, they exhibit multiple alterations in presynaptic organization and function. Profound depression and unusual periodic total transmission failures with repetitive stimulation point to a defect in vesicle mobilization/cycling, and these defects were mimicked in (+/+) NMJs by inhibitors of myosin light chain kinase, known to affect vesicle mobilization. Two separate release mechanisms, utilizing different endocytic machinery and Ca(2+) channels, were shown to coexist in (-/-) terminals, with the mature process targeted to presynaptic membrane opposed to muscle, and an abnormally retained immature process targeted to the remainder of the presynaptic terminal and axon. Thus, NCAM plays a critical and heretofore unsuspected role in the molecular organization of the presynaptic NMJ.}, Author = {Polo-Parada, L. and Bose, C. M. and Landmesser, L. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Electric Stimulation;Synaptic Vesicles;Research Support, Non-U.S. Gov't;Mice, Knockout;Neural Cell Adhesion Molecules;Presynaptic Terminals;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred C57BL;Neuromuscular Junction;Neurotransmitter Agents;Calcium Channels;Synaptic Transmission;Animals;Mice;24 Pubmed search results 2008}, Medline = {21603129}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.}, Pages = {815-28}, Pii = {S0896-6273(01)00521-9}, Pubmed = {11738028}, Title = {Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions}, Uuid = {921257D0-9222-42F6-9190-781A8665EFCC}, Volume = {32}, Year = {2001}} @article{Pologruto:2003, Abstract = {BACKGROUND: Laser scanning microscopy is a powerful tool for analyzing the structure and function of biological specimens. Although numerous commercial laser scanning microscopes exist, some of the more interesting and challenging applications demand custom design. A major impediment to custom design is the difficulty of building custom data acquisition hardware and writing the complex software required to run the laser scanning microscope. RESULTS: We describe a simple, software-based approach to operating a laser scanning microscope without the need for custom data acquisition hardware. Data acquisition and control of laser scanning are achieved through standard data acquisition boards. The entire burden of signal integration and image processing is placed on the CPU of the computer. We quantitate the effectiveness of our data acquisition and signal conditioning algorithm under a variety of conditions. We implement our approach in an open source software package (ScanImage) and describe its functionality. CONCLUSIONS: We present ScanImage, software to run a flexible laser scanning microscope that allows easy custom design.}, Author = {Pologruto, Thomas A. and Sabatini, Bernardo L. and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1475-925X}, Journal = {Biomed Eng Online}, Keywords = {Microscopy, Confocal;Signal Processing, Computer-Assisted;research support, u.s. gov't, p.h.s. ;Software Design;21 Neurophysiology;Software;evaluation studies;User-Computer Interface;Image Enhancement;24 Pubmed search results 2008;Equipment Design}, Month = {5}, Nlm_Id = {101147518}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA. pologrut\@cshl.org;}, Pages = {13}, Pii = {1475-925X-2-13}, Pubmed = {12801419}, Title = {ScanImage: flexible software for operating laser scanning microscopes}, Uuid = {6727EA3B-A5D7-44F2-8C60-62BA77D133CF}, Volume = {2}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1475-925X-2-13}} @article{Poluch:2007, Abstract = {During cerebral cortical development, gamma-aminobutyric acidergic (GABAergic) interneurons arise from a different site than projection neurons. GABAergic cells are generated in the subpallial ganglionic eminence (GE), while excitatory projection neurons arise from the neocortical ventricular zone. Our laboratory studies a model of cortical dysplasia that displays specific disruption of GABAergic mechanisms and an alteration in the overall balance of excitation in the neocortex. To produce this model, the birth of neurons on a specific gestational day in ferrets (embryonic day 33 [E33]) is interrupted by injection of the antimitotic methylazoxymethanol (MAM). We hypothesized that migration of interneurons might be disrupted in this cortical dysplasia paradigm. We observed that although interneurons migrate into the neocortex in both normal and dysplastic cortex, the migrating cells become disoriented over time after E33 MAM treatment. Coculture experiments using normal GE and MAM-treated cortex (and vice versa) demonstrate that cues dictating proper orientation of migrating interneurons arise from the cortex and are not intrinsic to the migrating cells. As a consequence, interneurons in mature brains of MAM-treated animals are abnormally distributed. We report that GABA(A) receptor activation is crucial to the proper positioning of interneurons migrating into the cortex from the GE in normal and MAM-treated animals.}, Author = {Poluch, and Jablonska, and Juliano,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Month = {4}, Nlm_Id = {9110718}, Organization = {Department of Anatomy, Physiology and Genetics, USUHS, Bethesda, MD 20814, USA.}, Pii = {bhm032}, Pubmed = {17443019}, Title = {Alteration of Interneuron Migration in a Ferret Model of Cortical Dysplasia}, Uuid = {4EBB882C-E90C-4DB7-A752-A2A2F5D0545F}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhm032}} @article{Poluektova:2005, Abstract = {Cognitive, behavioral, and motor impairments, during progressive human immunodeficiency virus type 1 (HIV-1) infection, are linked to activation of brain mononuclear phagocytes (MP; perivascular macrophages and microglia). Activated MPs effect a giant cell encephalitis and neuroinflammatory responses that are mirrored in severe combined immunodeficient (SCID) mice injected with human monocyte-derived macrophages (MDM). Whether activated human MDMs positioned in the basal ganglia affect hippocampal neuronal plasticity, the brain subregion involved in learning and memory, is unknown. Thus, immunohistochemical techniques were used for detection of newborn neurons (polysialylated neuronal cell adhesion molecule [PSA-NCAM]) and cell proliferation (Ki-67) to assay MDM effects on neuronal development in mouse models of HIV-1 encephalitis. Immunodeficient (C.B.-17/SCID and nonobese diabetic/SCID, NOD/SCID) and immune competent (C.B.-17) mice were injected with uninfected or HIV-1-infected MDM. Sham-operated or unmanipulated mice served as controls. Neuronal plasticity was evaluated in the hippocampal dentate gyrus (DG) at days 7 and 28. By day 7, increased numbers of Ki-67(+) cells, PSA-NCAM(+) cells and dendrites in DG were observed in sham-operated animals. In contrast, significant reductions in neuronal precursors and altered neuronal morphology paralleled increased microglial activation in both HIV-1-infected and uninfected MDM-injected animals. DG cellular composition was restored at day 28. We posit that activated MDM induce inflammation and diminish DG neuronal plasticity. These data provide novel explanations for the cognitive impairments manifested during advanced HIV-1 infection. (c) 2005 Wiley-Liss, Inc.}, Author = {Poluektova, and Meyer, and Walters, and Paez, and Gendelman,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {11 Glia}, Month = {8}, Nlm_Id = {8806785}, Organization = {Laboratory of Neuroregeneration, Department of Pharmacology and Experimental Neuroscience, Center for Neurovirology and Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, Nebraska.}, Pubmed = {16078235}, Title = {Macrophage-induced inflammation affects hippocampal plasticity and neuronal development in a murine model of HIV-1 encephalitis}, Uuid = {074C8CB9-92B2-4E18-925D-102778127A21}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20253}} @article{Pomerantz:2004, Abstract = {The goal of regenerative medicine is to restore form and function to damaged tissues. One potential therapeutic approach involves the use of autologous cells derived from the bone marrow (bone marrow-derived cells, BMDCs). Advances in nuclear transplantation, experimental heterokaryon formation and the observed plasticity of gene expression and phenotype reported in multiple phyla provide evidence for nuclear plasticity. Recent observations have extended these findings to show that endogenous cells within the bone marrow have the capacity to incorporate into defective tissues and be reprogrammed. Irrespective of the mechanism, the potential for new gene expression patterns by BMDCs in recipient tissues holds promise for developing cellular therapies for both proliferative and post-mitotic tissues.}, Author = {Pomerantz, Jason and Blau, Helen M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {review;Research Support, Non-U.S. Gov't;Totipotent Stem Cells;Bone Marrow Cells;08 Aberrant cell cycle;Regeneration;Stem Cells;Research Support, U.S. Gov't, P.H.S.;Gene Expression Regulation;22 Stem cells;Humans;Animals;24 Pubmed search results 2008;Cell Nucleus;Cytoplasm}, Month = {9}, Nlm_Id = {100890575}, Number = {9}, Organization = {Baxter Laboratory in Genetic Pharmacology and Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.}, Pages = {810-6}, Pii = {ncb0904-810}, Pubmed = {15340448}, Title = {Nuclear reprogramming: a key to stem cell function in regenerative medicine}, Uuid = {0A74CD49-1B4B-11DB-87EC-000D9346EC2A}, Volume = {6}, Year = {2004}, url = {papers/Pomerantz_NatCellBiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb0904-810}} @article{Ponomarev:2006, Abstract = {Microglial cells are monocytic lineage cells that reside in the CNS and have the capacity to become activated during various pathological conditions. Although it was demonstrated that activation of microglial cells could be achieved in vitro by the engagement of CD40-CD40L interactions in combination with proinflammatory cytokines, the exact factors that mediate activation of microglial cells in vivo during CNS autoimmunity are ill-defined. To investigate the role of CD40 in microglial cell activation during experimental autoimmune encephalomyelitis (EAE), we used bone marrow chimera mice that allowed us to distinguish microglial cells from peripheral macrophages and render microglial cells deficient in CD40. We found that the first step of microglial cell activation was CD40-independent and occurred during EAE onset. The first step of activation consisted of microglial cell proliferation and up-regulation of the activation markers MHC class II, CD40, and CD86. At the peak of disease, microglial cells underwent a second step of activation, which was characterized by a further enhancement in activation marker expression along with a reduction in proliferation. The second step of microglial cell activation was CD40-dependent and the failure of CD40-deficient microglial cells to achieve a full level of activation during EAE was correlated with reduced expansion of encephalitogenic T cells and leukocyte infiltration in the CNS, and amelioration of clinical symptoms. Thus, our findings demonstrate that CD40 expression on microglial cells is necessary to complete their activation process during EAE, which is important for disease progression.}, Author = {Ponomarev, Eugene D. and Shriver, Leah P. and Dittel, Bonnie N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:38 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {11 Glia}, Month = {2}, Nlm_Id = {2985117R}, Number = {3}, Organization = {Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53201.}, Pages = {1402-10}, Pii = {176/3/1402}, Pubmed = {16424167}, Title = {CD40 Expression by Microglial Cells Is Required for Their Completion of a Two-Step Activation Process during Central Nervous System Autoimmune Inflammation}, Uuid = {BA43445B-EFA5-4681-A51C-4AA58224687F}, Volume = {176}, Year = {2006}} @article{Ponti:2006, Abstract = {Protracted neurogenesis occurs at different postnatal stages in different brain locations, whereby leading to site-specific adult neurogenesis in some cases. No spontaneous genesis of neurons occurs in the cerebellum after the postnatal genesis of granule cells from the external germinal layer (EGL), a transitory actively proliferating zone which is thought to be exhausted before puberty. Here, we show the protracted genesis of newly generated neuronal precursors in the cerebellar cortex of young rabbits, persisting beyond puberty. Neuroblasts generated within an actively proliferating subpial layer thus extending the postnatal EGL are arranged to form thousands of tangential chains reminiscent of those responsible for cell migration in the forebrain subventricular zone. These subpial chains cover the whole cerebellar surface from the 2nd to the 5th month of life, then disappearing after puberty. In addition, we describe the appearance of similar groups of cells at the end of granule cell genesis in the mouse cerebellum, here limited to the short period of EGL exhaustion (4-5 days). These results show common features do exist in the postnatal reorganization of secondary germinal layers of brain and cerebellum at specific stages, parallel to differences in the slowing down of cerebellar neurogenesis among mammalian species.}, Author = {Ponti, and Peretto, and Bonfanti,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {0372762}, Organization = {Department of Veterinary Morphophysiology, University of Turin, Via Leonardo da Vinci 44, 10095 Grugliasco, Italy.}, Pii = {S0012-1606(06)00134-5}, Pubmed = {16581058}, Title = {A subpial, transitory germinal zone forms chains of neuronal precursors in the rabbit cerebellum}, Uuid = {2FEAADE6-43E4-4960-9242-EB9A831BD7E3}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2006.02.037}} @article{Popesco:2006, Abstract = {Extreme gene duplication is a major source of evolutionary novelty. A genome-wide survey of gene copy number variation among human and great ape lineages revealed that the most striking human lineage-specific amplification was due to an unknown gene, MGC8902, which is predicted to encode multiple copies of a protein domain of unknown function (DUF1220). Sequences encoding these domains are virtually all primate-specific, show signs of positive selection, and are increasingly amplified generally as a function of a species' evolutionary proximity to humans, where the greatest number of copies (212) is found. DUF1220 domains are highly expressed in brain regions associated with higher cognitive function, and in brain show neuron-specific expression preferentially in cell bodies and dendrites.}, Author = {Popesco, Magdalena C. and Maclaren, Erik J. and Hopkins, Janet and Dumas, Laura and Cox, Michael and Meltesen, Lynne and McGavran, Loris and Wyckoff, Gerald J. and Sikela, James M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {24 Pubmed search results 2008;19 Neocortical evolution}, Month = {9}, Nlm_Id = {0404511}, Number = {5791}, Organization = {Human Medical Genetics, University of Colorado at Denver and Health Sciences Center, Aurora, CO 80045, USA.}, Pages = {1304-7}, Pii = {313/5791/1304}, Pubmed = {16946073}, Title = {Human lineage-specific amplification, selection, and neuronal expression of DUF1220 domains}, Uuid = {7FBF4C30-9C18-49CA-A80A-D74A563A02BA}, Volume = {313}, Year = {2006}, url = {papers/Popesco_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1127980}} @article{Popovich:2001, Abstract = {Brain and spinal cord inflammation that develops after traumatic injury is believed to differentially influence the structural and/or physiological integrity of surviving neurons and glia. It is possible that the functional dichotomy of CNS inflammation results from the activity of a heterogeneous macrophage population elicited by trauma. Indeed, unique functions have been attributed to macrophages derived from resident microglia versus those originating from infiltrating monocytes. Thus, whether progressive tissue injury or repair is favored could be explained by the disproportionate contributions of one macrophage subset relative to the other. Descriptive neuroanatomical studies are a reasonable first approach to revealing a relationship between microglia, recruited blood monocytes/macrophages, and regions of tissue degeneration and/or repair. Unfortunately, it is not possible to differentiate between CNS macrophage subsets using conventional immunohistochemical approaches. In the present study, we have used radiation bone marrow chimeric rats to definitively characterize the macrophage reaction elicited by experimental spinal contusion injury. In chimeric animals, antibodies raised against unique cell surface molecules expressed on bone marrow-derived cells (BMCs) were used to distinguish infiltrating BMCs from resident microglial-derived macrophages. Our findings indicate that the onset and plateau of macrophage activation (previously shown to be 3 and 7 days postinjury, respectively) is dominated initially by microglial-derived macrophages and then is supplanted by hematogenous cells. While resident macrophages are ubiquitously distributed throughout the injury site, leukocyte-derived monocytes exclusively infiltrate the gray matter and to a lesser extent subpial white matter. Generally, monocyte foci in white matter remain associated with the lumen or abluminal surface of blood vessels, i.e. few cells actually infiltrate the parenchyma. If functional differences exist between CNS macrophage subsets, differences in the time-dependent accumulation and distribution of these cell types could differentially influence the survival of surrounding neurons and glia.}, Author = {Popovich, P. G. and Hickey, W. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Rats, Inbred Lew;Animals;Monocytes;Macrophages;Image Processing, Computer-Assisted;Rats;Bone Marrow Transplantation;Rats, Inbred BN;Microglia;Cell Count;11 Glia;Disease Models, Animal;Crosses, Genetic;Male;Radiation Chimera;Spinal Cord Injuries;Research Support, U.S. Gov't, P.H.S.;Wounds, Nonpenetrating;Wallerian Degeneration;Immunohistochemistry;Retrograde Degeneration}, Medline = {21337698}, Month = {7}, Nlm_Id = {2985192R}, Number = {7}, Organization = {Department of Molecular Virology, Immunology &Medica Genetics, The Ohio State University College of Medicine and Public Health, Columbus, USA.}, Pages = {676-85}, Pubmed = {11444796}, Title = {Bone marrow chimeric rats reveal the unique distribution of resident and recruited macrophages in the contused rat spinal cord}, Uuid = {22352207-F735-43EE-8A05-E53FA2309F85}, Volume = {60}, Year = {2001}} @article{Popovich:1993, Abstract = {Following contusion injury to the dorsal surface of thoracic rat spinal cord, major histocompatibility complex (MHC) class II (Ia) antigen expression by microglia was evaluated throughout the developing lesion. Past investigations of various central nervous system (CNS) lesions have examined short-term or acute sequelae of post-traumatic Ia expression. This report demonstrates that in animals allowed to recover for 18 (sub-chronic) and 45 (chronic) days post-injury, MHC class II antigen is expressed differently at rostral and caudal extents of the lesion as compared with the lesion's epicenter. Following contusion injury to the thoracic spinal cord, sub-chronically injured animals demonstrated Ia-positive microglial staining throughout the white matter rostral and caudal to the epicenter of the lesion, whereas Ia-positive microglia and/or perivascular cells are localized within the gray matter adjacent to it. MHC class II immunoreactivity is down-regulated on microglia at chronic survival times but clusters of Ia-positive macrophages are prominent in regions of maximal degeneration at the epicenter of the lesion. Our findings support the theory that two distinct populations of macrophages participate in resolving traumatic injury. One population is the parenchymal CNS microglia and the other is presumably exudate macrophages derived from the blood. Furthermore, the immunocompetence of these cells as measured by MHC expression may be differentially regulated. This hypothesis is based on differences in Ia-positive staining observed between microglia and macrophages over time concomitant with differences in the spatial distribution of these cell types.}, Author = {Popovich, P. G. and Streit, W. J. and Stokes, B. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0897-7151}, Journal = {J Neurotrauma}, Keywords = {Down-Regulation;Indicators and Reagents;Neuroglia;Rats, Sprague-Dawley;Spinal Cord Injuries;Rats;Female;Histocompatibility Antigens Class II;Not relevant;Immunohistochemistry;T-Lymphocytes;11 Glia;Contusions;Support, U.S. Gov't, P.H.S.;Animals}, Medline = {93308731}, Nlm_Id = {8811626}, Number = {1}, Organization = {Department of Physiology, Ohio State University, College of Medicine, Columbus.}, Pages = {37-46}, Pubmed = {8320731}, Title = {Differential expression of MHC class II antigen in the contused rat spinal cord}, Uuid = {A94ADCD3-8128-4CFB-A6E9-AC992CB18B7F}, Volume = {10}, Year = {1993}} @article{Porter:2005, Abstract = {The gamma-amino-butyric acid type A receptors (GABAAR) are a heteropentameric receptor complex, composed of 16 possible subunits in various combinations, forming a ligand-gated ion channel. Subunit composition is the primary determinant of GABAAR physiology and pharmacology. Here we have measured mRNA levels for 16 GABAAR subunits in isolated dentate granule neurons (DGN) from eight pediatric patients undergoing resective surgery for intractable epilepsy. We found tightly correlated expression of a subset of GABAAR subunit mRNAs within a single DGN (alpha1, gamma1, and gamma2; alpha4, alpha5, and beta2; alpha4 and beta3). Analysis of inter-patient variability (ANOVA) of eleven highly expressed GABAAR subunit mRNAs found seven of the subunits varied between patients, as did whole cell GABAAR currents. Due to inter-patient differences, there is heterogeneity in DGN GABAAR subunit mRNA and physiology within pediatric epilepsy patients. Patient-specific GABAAR expression might contribute to variability in anti-epileptic drug efficacy, side-effect profiles, and seizure susceptibility.}, Author = {Porter, Brenda E. and Zhang, Guojun and Celix, Juanita and Hsu, Fu-chun C. and Raol, YogendraSinh H. and Telfeian, Albert and Gallagher, Paul R. and Coulter, Douglas A. and Brooks-Kayal, Amy R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0969-9961}, Journal = {Neurobiol Dis}, Keywords = {Epilepsy;Adolescent;21 Neurophysiology;Hippocampus;Comparative Study;Research Support, U.S. Gov't, P.H.S.;Gene Expression Regulation;Protein Subunits;Child, Preschool;Child;RNA, Messenger;Humans;24 Pubmed search results 2008;21 Epilepsy;Receptors, GABA-A}, Month = {4}, Nlm_Id = {9500169}, Number = {3}, Organization = {Division of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA. porterb\@email.chop.edu}, Pages = {484-91}, Pii = {S0969-9961(04)00321-3}, Pubmed = {15755675}, Title = {Heterogeneous GABAA receptor subunit expression in pediatric epilepsy patients}, Uuid = {7A6B3822-6DE5-42CA-9B8F-B89A70562A79}, Volume = {18}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.nbd.2004.12.010}} @article{Porter:2003, Abstract = {BACKGROUND: Risk factors for temporal lobe epilepsy (TLE) include history of CNS infection, family history of epilepsy, and history of febrile convulsions (FC). Pre-existing cortical dysplasia (CD) may also predispose to refractory TLE, independent of other risk factors for epilepsy. METHODS: The authors reviewed the neuropathologic features of surgical tissue from temporal lobectomies of 33 pediatric patients with refractory TLE, with and without a history of epilepsy risk factors. RESULTS: CD was found in 64\%(21/33) of all patients with refractory TLE, including 73\%(11/15) patients with a history of FC, 66\%(2/3) patients with CNS infections, and 83\%(5/6) patients with a family history of epilepsy. Disrupted cortical lamination, dystrophic and maloriented neurons, and balloon cells characterized the CD found in the temporal neocortex. CONCLUSION: CD was seen in 21 of 33 surgical specimens from children with refractory TLE, including those with and without other epilepsy risk factors.}, Author = {Porter, B. E. and Judkins, A. R. and Clancy, R. R. and Duhaime, A. and Dlugos, D. J. and Golden, J. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1526-632X}, Journal = {Neurology}, Keywords = {Causality;10 Development;Follow-Up Studies;Humans;Treatment Outcome;Risk Factors;Neocortex;Female;Child;Hippocampus;21 Dysplasia-heterotopia;research support, non-u.s. gov't;Brain Diseases;Male;Epilepsy, Temporal Lobe;21 Neurophysiology;10 genetics malformation;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0401060}, Number = {3}, Organization = {Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia, and Department of Pediatrics and Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. Porterb\@email.chop.edu}, Pages = {365-8}, Pubmed = {12913199}, Title = {Dysplasia: a common finding in intractable pediatric temporal lobe epilepsy}, Uuid = {858F019B-21F2-4D9F-A885-8FF635DCE547}, Volume = {61}, Year = {2003}} @article{Portera-Cailliau:2005, Abstract = {The development of axonal arbors is a critical step in the establishment of precise neural circuits, but relatively little is known about the mechanisms of axonal elaboration in the neocortex. We used in vivo two-photon time-lapse microscopy to image axons in the neocortex of green fluorescent protein-transgenic mice over the first 3 wk of postnatal development. This period spans the elaboration of thalamocortical (TC) and Cajal-Retzius (CR) axons and cortical synaptogenesis. Layer 1 collaterals of TC and CR axons were imaged repeatedly over time scales ranging from minutes up to days, and their growth and pruning were analyzed. The structure and dynamics of TC and CR axons differed profoundly. Branches of TC axons terminated in small, bulbous growth cones, while CR axon branch tips had large growth cones with numerous long filopodia. TC axons grew rapidly in straight paths, with frequent interstitial branch additions, while CR axons grew more slowly along tortuous paths. For both types of axon, new branches appeared at interstitial sites along the axon shaft and did not involve growth cone splitting. Pruning occurred via retraction of small axon branches (tens of microns, at both CR and TC axons) or degeneration of large portions of the arbor (hundreds of microns, for TC axons only). The balance between growth and retraction favored overall growth, but only by a slight margin. Given the identical layer 1 territory upon which CR and TC axons grow, the differences in their structure and dynamics likely reflect distinct intrinsic growth programs for axons of long projection neurons versus local interneurons.}, Author = {Portera-Cailliau, and Weimer, and Paola, and Caroni, and Svoboda,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {10 Development;plasticity;structural remodeling;Structure-Activity Relationship;imaging;in vivo;Optics;microscopy;Multiphoton;neocortex;axons;Synapses;Recombinant Fusion Proteins;Female;Research Support, U.S. Gov't, P.H.S.;Promoter Regions (Genetics);Neocortex;Growth Cones;Research Support, N.I.H., Extramural;Mice, Transgenic;Microscopy, Fluorescence, Multiphoton;10 Structural plasticity;Green Fluorescent Proteins;Animals;Mice;Male;Axons}, Month = {7}, Nlm_Id = {101183755}, Number = {8}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, United States of America.}, Pages = {e272}, Pii = {05-PLBI-RA-0321R1}, Pubmed = {16026180}, Title = {Diverse Modes of Axon Elaboration in the Developing Neocortex}, Uuid = {4633FC26-872A-4119-9C8C-9BBD7188C849}, Volume = {3}, Year = {2005}, url = {papers/Portera-Cailliau_PLoSBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0030272}} @article{Posnett:2001, Abstract = {We usually think of superantigens (SAg) as dangerous toxins that may cause toxic shock syndrome and death. Now, based on two papers in this issue of Immunity, it seems that we all have SAg genes within us, lying dormant and waiting to be activated under special circumstances.}, Author = {Posnett, D. N. and Yarilina, A. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1074-7613}, Journal = {Immunity}, Keywords = {15 ERVs retroelements;Endogenous Retroviruses;Virus Diseases;24 Pubmed search results 2008;T-Lymphocytes;Mammary Tumor Virus, Mouse;comment;15 Retrovirus mechanism;Humans;Superantigens;Lymphocyte Activation;review;Antigens, Viral}, Medline = {21527022}, Month = {10}, Nlm_Id = {9432918}, Number = {4}, Organization = {Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. dposnett\@med.cornell.edu}, Pages = {503-6}, Pii = {S1074761301002114}, Pubmed = {11672533}, Title = {Sleeping with the enemy--endogenous superantigens in humans}, Uuid = {1F9D3C38-F424-481F-B659-086D9B200AF2}, Volume = {15}, Year = {2001}} @article{Poulet:2008, Abstract = {Internal brain states form key determinants for sensory perception, sensorimotor coordination and learning. A prominent reflection of different brain states in the mammalian central nervous system is the presence of distinct patterns of cortical synchrony, as revealed by extracellular recordings of the electroencephalogram, local field potential and action potentials. Such temporal correlations of cortical activity are thought to be fundamental mechanisms of neuronal computation. However, it is unknown how cortical synchrony is reflected in the intracellular membrane potential (V(m)) dynamics of behaving animals. Here we show, using dual whole-cell recordings from layer 2/3 primary somatosensory barrel cortex in behaving mice, that the V(m) of nearby neurons is highly correlated during quiet wakefulness. However, when the mouse is whisking, an internally generated state change reduces the V(m) correlation, resulting in a desynchronized local field potential and electroencephalogram. Action potential activity was sparse during both quiet wakefulness and active whisking. Single action potentials were driven by a large, brief and specific excitatory input that was not present in the V(m) of neighbouring cells. Action potential initiation occurs with a higher signal-to-noise ratio during active whisking than during quiet periods. Therefore, we show that an internal brain state dynamically regulates cortical membrane potential synchrony during behaviour and defines different modes of cortical processing.}, Author = {Poulet, James F. A. and Petersen, Carl C. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {24 Pubmed search results 2008;Electroencephalography;research support, non-u.s. gov't;Exploratory Behavior;Wakefulness;Mice, Inbred C57BL;Somatosensory Cortex;Animals;Male;Membrane Potentials;Mice;Neurons}, Month = {8}, Nlm_Id = {0410462}, Number = {7206}, Organization = {Laboratory of Sensory Processing, Brain Mind Institute, Faculty of Life Sciences, Ecole Polytechnique F{\'e}d{\'e}rale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.}, Pages = {881-5}, Pii = {nature07150}, Pubmed = {18633351}, Title = {Internal brain state regulates membrane potential synchrony in barrel cortex of behaving mice}, Uuid = {977A9D72-10F5-4F65-9660-F2FC4E2FF84D}, Volume = {454}, Year = {2008}, url = {papers/Poulet_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature07150}} @article{Poulsen:1999, Abstract = {Following intraperitoneal (IP) inoculation of neonatal mice, the polytropic recombinant murine leukemia virus (MuLV), Fr98, induces a severe brain disease characterized by ataxia, seizures and death. In contrast, no apparent clinical neurological disease is seen after IP infection with Fr54, a polytropic MuLV differing from Fr98 in its envelope gene sequences. In the brain both Fr98 and Fr54 infect primarily capillary endothelial cells and microglia. However, the level of microglial infection by Fr98 is twofold higher than by Fr54, which might account for the difference in neurovirulence. In the present study, in order to test directly whether an increase in the number of microglia infected by Fr54 would be sufficient to induce clinical disease, we attempted to increase the level of Fr54 in the brain by changing the route of infection. After intraventricular inoculation with Fr54-infected neural stem cells (clone C17.2), a well-established vehicle for delivery of viruses and genes to the brain, mice became ataxic and died 4 weeks postinfection. In these mice induction of brain disease was correlated with a higher level of viral antigen in the cerebrum and an increase in the number of infected microglial cells in all brain regions examined compared with mice inoculated IP. In contrast, mice inoculated with neural stem cells infected with an ecotropic nonneurovirulent murine leukemia virus, FB29, developed no clinical disease in spite of evidence for widespread infection of microglia in brain. Since the main differences between Fr54 and FB29 are in the SU (gp70) region of the envelope gene, this region is most likely to account for the differences in induction of CNS disease seen in the current experiments.}, Author = {Poulsen, D. J. and Favara, C. and Snyder, E. Y. and Portis, J. and Chesebro, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {Animals;Tumor Virus Infections;Recombinant Proteins;Microglia;Capsid;Brain;Not relevant;11 Glia;Brain Diseases;Leukemia Virus, Murine;Viral Envelope Proteins;Retroviridae Infections;Mice, Inbred Strains;Neurons;Viral Load;Mice;Virulence;Stem Cells}, Medline = {20013306}, Month = {10}, Nlm_Id = {0110674}, Number = {1}, Organization = {Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories, Hamilton, Montana 59840, USA.}, Pages = {23-9}, Pii = {S0042682299999178}, Pubmed = {10544079}, Title = {Increased neurovirulence of polytropic mouse retroviruses delivered by inoculation of brain with infected neural stem cells}, Uuid = {62B7BE58-83D3-4122-9D75-2729C5B20E08}, Volume = {263}, Year = {1999}, url = {papers/Poulsen_Virology1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/viro.1999.9917}} @article{Poulter:1992, Abstract = {The expression of mRNAs coding for alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6 subunits of the GABAA neurotransmitter receptor was followed during the development of the rat CNS by in situ hybridization histochemistry. Expression of these subunit mRNAs in tissue sections of embryonic day 15 and 17 (E15, E17) whole rat and in brain at ages greater than E17 to adult were varied, transient, and region specific. Subunit mRNAs first detected at E15 were those coding for the alpha 2 and alpha 3 subunits. At E17, alpha 2, alpha 3, and alpha 5 mRNAs were present in abundance in numerous areas in the CNS, with lower but significant amounts of alpha 6 being present in the cortical neuroepithelial layers. However, alpha 6 subunit mRNA expression in the cortex declined until little or no alpha 6 mRNA was detected at E19. alpha 1 subunit mRNA first appeared at E19 in the cortex, followed by expression in the hippocampus by postnatal 5 (PN5). Particularly high expression of alpha 2 and alpha 5 subunit mRNAs was detected throughout the developing CNS, but they were most abundant in the olfactory bulb neurons. The high levels of alpha 2 and alpha 5 subunit mRNAs began to decline around PN5 to the amounts observed in adult. These results demonstrate that numerous GABAA receptor alpha-subunits are expressed before birth in a region- and age-specific manner. This complex and varied expression supports the hypothesis that GABA may play a role in cellular and synaptic differentiation.}, Author = {Poulter, M. O. and Barker, J. L. and O'Carroll, A. M. and Lolait, S. J. and Mahan, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Neurosci}, Keywords = {Base Sequence;Tissue Distribution;Molecular Sequence Data;Rats;Oligonucleotide Probes/genetics;Time Factors;Receptors, GABA-A/*genetics;*Fetal Development;Animal;Fetus/*metabolism;RNA, Messenger/*metabolism;Animals, Newborn;I-1;Brain/embryology/growth &development/*metabolism;13 Olfactory bulb anatomy}, Number = {8}, Organization = {Laboratories of Neurophysiology, NINDS, NIH, Bethesda, Maryland 20892.}, Pages = {2888-900.}, Title = {Differential and transient expression of GABAA receptor alpha-subunit mRNAs in the developing rat CNS}, Uuid = {FB3D447F-9C22-44B4-AB26-D95933014DB4}, Volume = {12}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1322978}} @article{Povinelli:1995, Abstract = {Traditional analyses of the evolution of intelligence have emphasized commonality and continuity among species. However, recent research suggests that humans might have specialized in a particular kind of intelligence that is related to understanding mental states such as desires, intentions and beliefs. Data indicate that the ability to reflect on one's own mental states, as well as those of others, might be the result of evolutionary changes in the prefrontal cortex. Behavioral studies in children and chimpanzees reveal both similarities and striking differences in the developmental pathways that lead to theory-of-mind capacities. Humans and great apes share many ancient patterns of social behavior, but it is too early to be certain if they interpret them in the same manner. Humans might have evolved a cognitive specialization in theory of mind, forever altering their view of the social universe. 0166-2236 Journal Article Review Review, Tutorial}, Author = {Povinelli, D. J. and Preuss, T. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Trends Neurosci}, Keywords = {18 Classic Neuroanatomy Physiology;Brain/*physiology;Human;M;Support, U.S. Gov't, P.H.S.;*Evolution;Support, Non-U.S. Gov't;Animals;Cognition/*physiology}, Number = {9}, Organization = {Laboratory of Comparative Behavioral Biology, New Iberia Research Center, LA 70560, USA.}, Pages = {418-24}, Pubmed = {7482808}, Title = {Theory of mind: evolutionary history of a cognitive specialization}, Uuid = {F39316D4-8C3B-4573-958E-C67CA4E7F444}, Volume = {18}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7482808}} @article{Powell:1999, Abstract = {Transgenic mice overexpressing cytokines facilitate analysis of the effects of these immunomodulators on indigenous cells of the central nervous system. This study examines morphological aspects of demyelination and permeability changes, in a recently described transgenic model (termed GFAP-IL3). GFAP-IL3 mice develop progressive motor disease at approximately 5 months. Lesions identified after disease onset, showed activation of microglia, astroglial proliferation with phagocytosis of lipids, and immigration of macrophages and mast cells into neural parenchyma. Lymphocytes failed to appear until the later stages of the disease. Later, cerebellar and brain stem white matter contained focal demyelinating lesions with intense macrophage infiltration and a proliferative astrocytosis. Dystrophic axonal changes were noted, in addition to demyelination in heavily infiltrated lesions. Mast cells, variably present in the thalamus and meninges of wild type mice, were greatly increased at these sites in GFAP-IL3 mice. Blood-brain barrier (BBB) defects were documented with leakage of intravenously injected horseradish peroxidase. Mast cell infiltration into the CNS and their degranulation at the site of injury, may represent initial events in a spontaneous process of macrophage mediated demyelination in which glial cells and macrophages are both involved in the phagocytic process.}, Author = {Powell, H. C. and Garrett, R. S. and Brett, F. M. and Chiang, C. S. and Chen, E. and Masliah, E. and Campbell, I. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1015-6305}, Journal = {Brain Pathol}, Keywords = {Phagocytosis;Animals;Astrocytes;Brain;Axons;Interleukin-3;Mice, Transgenic;Not relevant;11 Glia;Blood-Brain Barrier;Axonal Transport;Organ Specificity;Neuroglia;Horseradish Peroxidase;Support, U.S. Gov't, P.H.S.;Support, U.S. Gov't, Non-P.H.S.;Cerebellum;Mice;Cell Division;Demyelinating Diseases;Mast Cells;Glial Fibrillary Acidic Protein}, Medline = {99235145}, Month = {4}, Nlm_Id = {9216781}, Number = {2}, Organization = {Veterans Administration Research Service, VAMC San Diego, La Jolla, CA, USA. hpowell\@ucsd.edu}, Pages = {219-35}, Pubmed = {10219739}, Title = {Response of glia, mast cells and the blood brain barrier, in transgenic mice expressing interleukin-3 in astrocytes, an experimental model for CNS demyelination}, Uuid = {35637761-95B3-4940-9E59-965B5F10BCC2}, Volume = {9}, Year = {1999}} @article{Pozniak:2006, Abstract = {ABSTRACT : Adult neurogenesis in the hippocampus is under complex genetic control. A recent comparative study of two inbred mouse strains using quantitative trait locus analysis has revealed that cell survival is most highly correlated with neurogenesis and identified candidate genes for further investigation.}, Author = {Pozniak, and Pleasure,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1465-6914}, Journal = {Genome Biol}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {100960660}, Number = {3}, Organization = {Department of Neurology, Programs in Neuroscience and Developmental Biology, University of California, San Francisco, CA 94143, USA,. sam.pleasure\@ucsf.edu.}, Pages = {207}, Pii = {gb-2006-7-3-207}, Pubmed = {16584531}, Title = {Genetic control of hippocampal neurogenesis}, Uuid = {E1EC7D9A-2906-44BE-AACB-F802A01FD705}, Volume = {7}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/gb-2006-7-3-207}} @article{Prasanth:2002, Abstract = {Origin recognition complex (ORC) proteins serve as a landing pad for the assembly of a multiprotein prereplicative complex, which is required to initiate DNA replication. During mitosis, the smallest subunit of human ORC, Orc6, localizes to kinetochores and to a reticular-like structure around the cell periphery. As chromosomes segregate during anaphase, the reticular structures align along the plane of cell division and some Orc6 localizes to the midbody before cells separate. Silencing of Orc6 expression by small interfering RNA (siRNA) resulted in cells with multipolar spindles, aberrant mitosis, formation of multinucleated cells, and decreased DNA replication. Prolonged periods of Orc6 depletion caused a decrease in cell proliferation and increased cell death. These results implicate Orc6 as an essential gene that coordinates chromosome replication and segregation with cytokinesis. 1095-9203 Journal Article}, Author = {Prasanth, S. G. and Prasanth, K. V. and Stillman, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Science}, Keywords = {Human;EE both;Animals;Centromere/metabolism;Cells, Cultured;Recombinant Fusion Proteins/analysis;Fluorescent Antibody Technique;Transfection;Mitosis;Phenotype;*Chromosome Segregation;Kinetochores/metabolism;RNA, Small Interfering;08 Aberrant cell cycle;Cell Line;Bromodeoxyuridine/metabolism;DNA-Binding Proteins/genetics/metabolism/*physiology;Tumor Cells, Cultured;Gene Silencing;Support, U.S. Gov't, P.H.S.;Mitotic Spindle Apparatus/ultrastructure;Polyploidy;RNA, Untranslated/metabolism/pharmacology;*DNA Replication;Cell Nucleus/metabolism;Cell Death;Chromosomes, Human/*metabolism;*Cell Division}, Number = {5583}, Organization = {Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11724, USA.}, Pages = {1026-31}, Title = {Orc6 involved in DNA replication, chromosome segregation, and cytokinesis}, Uuid = {93811CEF-EDC6-4877-9DA7-1B707C4692AB}, Volume = {297}, Year = {2002}, url = {papers/Prasanth_Science2002.pdf}} @article{Prat:2005, Abstract = {PURPOSE OF REVIEW: The aim of this article is to describe recent observations regarding the basis for the initiation and disease evolution of multiple sclerosis. RECENT FINDINGS: A current debate is where and what initiates the neuroinflammatory reaction that characterizes the acute multiple sclerosis lesion. Immune sensitization to neural antigens could develop within the systemic compartment consequent to exposure to cross-reacting, possibly viral derived, peptides (molecular mimicry). Although CD4 T cells are considered central to initiating central nervous system inflammation, the actual extent and specificity of tissue injury reflects the array of adaptive (CD8 T cells and antibody) and innate (microglia/macrophages) immune constituents present in the lesions. Neuropathologic studies indicate that lethal changes in neural cells (oligodendrocytes) could also be the initiating event, reflecting as yet unidentified acquired insults (e.g. exogenous virus or reactivated endogenous retrovirus) or intrinsic abnormalities ('neurodegenerative' hypothesis). Recurrence or persistence of the disease process can reflect events occurring at multiple sites including expansion of the immune repertoire in response to neural antigens transported to regional lymph nodes (determinant spreading), especially if immune regulatory mechanisms are defective; alterations in blood-brain barrier properties consequent to initial cellular transmigration; and participation of endogenous (microglia, astrocytes) or long lived infiltrating cells (macrophages, B cells in ectopic germinal centers) in regulating and effecting immune functions within the central nervous system. Accumulating neurologic deficit reflects the balance between injury and repair; the latter also being negatively or positively (trophic support and clearance of tissue debris) impacted by inflammatory processes. SUMMARY: Understanding the full spectrum of multiple sclerosis presents a continuing challenge for both immunology and neurobiology.}, Author = {Prat, Alexandre and Antel, Jack}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1350-7540}, Journal = {Curr Opin Neurol}, Keywords = {15 ERVs retroelements;Multiple Sclerosis;Blood-Brain Barrier;T-Lymphocytes;Encephalomyelitis, Autoimmune, Experimental;15 Retrovirus mechanism;Animals;Disease Progression;Humans;review;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {9319162}, Number = {3}, Organization = {Neuroimmunology Laboratory and Multiple Sclerosis Clinic, CHUM Notre-Dame Hospital, Montreal, Quebec, Canada.}, Pages = {225-30}, Pii = {00019052-200506000-00004}, Pubmed = {15891404}, Title = {Pathogenesis of multiple sclerosis}, Uuid = {AC0D9B35-ED30-42B2-8CFE-D433C52B6EAC}, Volume = {18}, Year = {2005}} @article{Pratt:2003, Abstract = {Competitive synaptic remodeling is an important feature of developmental plasticity, but the molecular mechanisms remain largely unknown. Calcium/calmodulin-dependent protein kinase II (CaMKII) can induce postsynaptic changes in synaptic strength. We show that postsynaptic CaMKII also generates structural synaptic rearrangements between cultured cortical neurons. Postsynaptic expression of activated CaMKII (T286D) increased the strength of transmission between pairs of pyramidal neuron by a factor of 4, through a modest increase in quantal amplitude and a larger increase in the number of synaptic contacts. Concurrently, T286D reduced overall excitatory synaptic density and increased the proportion of unconnected pairs. This suggests that connectivity from some synaptic partners was increased while other partners were eliminated. The enhancement of connectivity required activity and NMDA receptor activation, while the elimination did not. These data suggest that postsynaptic activation of CaMKII induces a structural remodeling of presynaptic inputs that favors the retention of active presynaptic partners.}, Author = {Pratt, Kara G. and Watt, Alanna J. and Griffith, Leslie C. and Nelson, Sacha B. and Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Fluorescent Dyes;Excitatory Amino Acid Antagonists;24 Pubmed search results 2008;Green Fluorescent Proteins;Lysine;Immunohistochemistry;Luminescent Proteins;Cerebral Cortex;Animals;Quaternary Ammonium Compounds;Rats, Long-Evans;Synaptic Transmission;Cell Count;Transfection;Organ Culture Techniques;Calcium-Calmodulin-Dependent Protein Kinase Type 2;Synapses;Drug Interactions;research support, u.s. gov't, non-p.h.s.;research support, u.s. gov't, p.h.s.;Cell Surface Extensions;Dizocilpine Maleate;Alanine;Neuronal Plasticity;Mutation;comparative study;Gene Expression Regulation, Enzymologic;Synapsins;Anesthetics, Local;Tetrodotoxin;Rats;Aspartic Acid;Ca(2+)-Calmodulin Dependent Protein Kinase;Threonine;Animals, Newborn;21 Neurophysiology;Valine;Calcium-Calmodulin-Dependent Protein Kinases;Neurons;Pyridinium Compounds;Nerve Tissue Proteins;Excitatory Postsynaptic Potentials}, Month = {7}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Biology, Volen National Center for Complex Systems, Brandeis University, Waltham, MA 02454, USA.}, Pages = {269-81}, Pii = {S0896627303004227}, Pubmed = {12873384}, Title = {Activity-dependent remodeling of presynaptic inputs by postsynaptic expression of activated CaMKII}, Uuid = {0C0B370E-794D-4582-A8B8-590E12E98943}, Volume = {39}, Year = {2003}, url = {papers/Pratt_Neuron2003.pdf}} @article{Prem-veer-Reddy:1980, Abstract = {In the DNA-synthesizing phase (S phase) of CHEF/18 Chinese hamster embryo fibroblast cells, six enzymes associated with DNA metabolism, including DNA polymerase (deoxynucleoside triphosphate:DNA deoxynucleotidyl-transferase, EC 2.7.7.7), were largely localized in the nuclear region (karyoplasts). By contrast, in quiescent and G1 phase cells these enzymatic activites were mainly absent from the nucleus and were recovered in the cytoplasmic portion (cytoplasts). These nuclear (but not cytoplasmic) enzymatic activities cosedimented rapidly on sucrose density gradients. Further, the rapidly sedimenting enzyme activities were unique to cells in S phase. An organized supramolecular structure that allows channeling of metabolites into DNA was demonstrated by kinetics of nucleotide incorporation. "Permeabilized" cells selectively channeled incorporation of ribonucleoside diphosphates into DNA in preference to deoxyribonucleoside triphosphates. Deoxyribonucleoside triphosphate incorporation occurred when ribonucleoside-diphosphate reductase (2'-deoxyribonucleoside-diphosphate: oxidized-thioredoxin 2'-oxidoreductase, EC 1.17.4.1) activity was abolished by hydroxyurea. Our interpretation is that during DNA replication, the nucleus contains a complex of DNA precursor-synthesizing enzymes juxtaposed with the "replication apparatus" comprising DNA polymerase, other enzymes, and structural proteins. Functional integrity of this structure is impaired when one of its essential components is inactivated. We propose the name "replitase" for this multienzyme complex for DNA replication and suggest that it incorporates precursors rapidly and efficiently. Possibly its assembly signals the initiation of the S phase of the cell cycle.}, Author = {Prem veer Reddy, G. and Pardee, A. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Hamsters;Ribonucleoside Diphosphate Reductase;Nucleoside-Diphosphate Kinase;Animals;Cells, Cultured;Thymidine Kinase;Cell Cycle;Fibroblasts;Cytoplasm;15 Retrovirus mechanism;Ribonucleosides;DNA Replication;Tetrahydrofolate Dehydrogenase;Multienzyme Complexes;Cricetulus;DNA Polymerase II;DNA-Directed DNA Polymerase;Research Support, U.S. Gov't, P.H.S.;Thymidylate Synthase;Cell Compartmentation;Nucleoside-Phosphate Kinase;Cell Nucleus;24 Pubmed search results 2008;Cytidine Monophosphate;Deoxyribonucleosides}, Medline = {81013874}, Month = {6}, Nlm_Id = {7505876}, Number = {6}, Pages = {3312-16}, Pubmed = {6251456}, Title = {Multienzyme complex for metabolic channeling in mammalian DNA replication}, Uuid = {6D29909F-B4E4-48B2-891C-D048357AF3A6}, Volume = {77}, Year = {1980}} @article{Prescott:2005, Abstract = {Neurons of the visual, auditory and vestibular systems that signal through graded changes in membrane potential rely upon synaptic ribbons for the exquisite control of neurotransmitter release. Although clearly important for tonic neurotransmission, the precise role of synaptic ribbons remains elusive. In recent years, several genetic, biochemical, electrophysiological and optical approaches have begun to shed light on the functions of these enigmatic organelles.}, Author = {Prescott, Elizabeth D. and Zenisek, David}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Synapses;Synaptic Vesicles;research support, non-u.s. gov't;Eye Proteins;Exocytosis;research support, n.i.h., extramural;research support, u.s. gov't, p.h.s.;Animals;Humans;24 Pubmed search results 2008;review}, Month = {8}, Nlm_Id = {9111376}, Number = {4}, Organization = {Department of Cellular and Molecular Physiology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06511, USA.}, Pages = {431-6}, Pii = {S0959-4388(05)00107-8}, Pubmed = {16023852}, Title = {Recent progress towards understanding the synaptic ribbon}, Uuid = {54D96AC4-51DB-48DB-BF09-C87C5619DB4A}, Volume = {15}, Year = {2005}, url = {papers/Prescott_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.07.005}} @article{Price:1970, Author = {Price, J. L. and Powell, T. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0021-9533}, Journal = {J Cell Sci}, Keywords = {Synapses;Synaptic Vesicles;Synaptic Membranes;Dendrites;Limbic System;Microscopy, Electron;Rats;Animals;13 Olfactory bulb anatomy;Axons}, Medline = {71027124}, Month = {7}, Nlm_Id = {0052457}, Number = {1}, Pages = {125-55}, Pubmed = {5476853}, Title = {The synaptology of the granule cells of the olfactory bulb}, Uuid = {FBEC19CF-D067-11DA-8A8C-000D9346EC2A}, Volume = {7}, Year = {1970}} @article{Price:1987, Abstract = {We describe a cell-lineage marking system applicable to the vertebrate nervous system. The basis of the technique is gene transfer using the retroviral vector system. We used Escherichia coli beta-galactosidase as a marker gene and demonstrate a high level of expression of this marker from the viral long terminal repeat promoter, with simultaneous expression of the Tn5 neo gene from the simian virus 40 early promoter. This expression has allowed us to detect individual infected cells histochemically. We applied this marking technique to the study of lineage relationships in the developing vertebrate nervous system, both in vivo and in culture. In the rat retina, we injected virus in vivo and histochemically identified clones of marked neural cells. In addition, we used this virus to infect cultures of rat cerebral cortex and have analyzed the clonal relationships of morphologically different neural cell types. The host range of the marking system extends to avian as well as mammalian species. Thus, this system should have broad applicability as a means of gene transfer and expression in the nervous system.}, Author = {Price, J. and Turner, D. and Cepko, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Retina;10 Development;Rats, Inbred F344;Research Support, Non-U.S. Gov't;Rats;Cell Line;Retroviridae;Research Support, U.S. Gov't, P.H.S.;Astrocytes;Genes;Nervous System;beta-Galactosidase;Animals;Culture Techniques;24 Pubmed search results 2008;Cerebral Cortex;Cloning, Molecular}, Medline = {87092353}, Month = {1}, Nlm_Id = {7505876}, Number = {1}, Pages = {156-60}, Pubmed = {3099292}, Title = {Lineage analysis in the vertebrate nervous system by retrovirus-mediated gene transfer}, Uuid = {B207B4E6-EE2B-11DA-8605-000D9346EC2A}, Volume = {84}, Year = {1987}, url = {papers/Price_ProcNatlAcadSciUSA1987.pdf}} @article{Priller:2003, Abstract = {While the brain has traditionally been considered a rather secluded site, recent studies suggest that adult bone marrow (BM)-derived stem cells can generate glia and neurons in rodents and humans. Macrophages and microglia are the first to appear in the murine brain after transplantation of genetically marked BM cells. Within weeks after transplantation, some authors have found astrocytes and cells expressing neuronal antigens. We detected cerebellar Purkinje neurons and interneurons, such as basket cells, expressing the green fluorescent protein (GFP) 10-15 months after transplantation of GFP-labeled BM cells. The results push the boundaries of our classic view of lineage restriction.}, Author = {Priller, Josef}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0948-6143}, Journal = {Histochem Cell Biol}, Keywords = {Cell Differentiation;Purkinje Cells;Astrocytes;Animals;Humans;Stem Cell Transplantation;Neuronal Plasticity;lectures;Bone Marrow Transplantation;Brain;Microglia;11 Glia;Green Fluorescent Proteins;Histocytochemistry;Adult;Transplantation Tolerance;Mice;Luminescent Proteins}, Medline = {22800872}, Month = {8}, Nlm_Id = {9506663}, Number = {2}, Organization = {Department of Neurology, Charit{\'e}, Humboldt-University, Schumannstrasse 20/21, 10117 Berlin, Germany. josef.priller\@charite.de}, Pages = {85-91}, Pubmed = {12898276}, Title = {Robert Feulgen Prize Lecture. Grenzg{\"a}nger: adult bone marrow cells populate the brain}, Uuid = {BBBD75FA-04FF-4C87-A032-089E16E8FBDE}, Volume = {120}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00418-003-0559-7}} @article{Priller:2001, Abstract = {The versatility of stem cells has only recently been fully recognized. There is evidence that upon adoptive bone marrow (BM) transplantation (BMT), donor-derived cells can give rise to neuronal phenotypes in the brains of recipient mice. Yet only few cells with the characteristic shape of neurons were detected 1-6 mo post-BMT using transgenic or newborn mutant mice. To evaluate the potential of BM to generate mature neurons in adult C57BL/6 mice, we transferred the enhanced green fluorescent protein (GFP) gene into BM cells using a murine stem cell virus-based retroviral vector. Stable and high level long-term GFP expression was observed in mice transplanted with the transduced BM. Engraftment of GFP-expressing cells in the brain was monitored by intravital microscopy. In a long-term follow up of 15 mo post-BMT, fully developed Purkinje neurons were found to express GFP in both cerebellar hemispheres and in all chimeric mice. GFP-positive Purkinje cells were also detected in BM chimeras from transgenic mice that ubiquitously express GFP. Based on morphologic criteria and the expression of glutamic acid decarboxylase, the newly generated Purkinje cells were functional.}, Author = {Priller, J. and Persons, D. A. and Klett, F. F. and Kempermann, G. and Kreutzberg, G. W. and Dirnagl, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {Purkinje Cells;Transduction, Genetic;Microscopy, Immunoelectron;Animals;Stem Cell Transplantation;Bone Marrow Transplantation;Microscopy, Confocal;Mice, Inbred C57BL;Recombinant Fusion Proteins;Retroviridae;Male;Hematopoietic Stem Cell Transplantation;Green Fluorescent Proteins;Transplantation Chimera;Bone Marrow Cells;Transplantation, Isogeneic;Cell Transplantation;Flow Cytometry;Cerebellum;Mice;Luminescent Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {21581896}, Month = {11}, Nlm_Id = {0375356}, Number = {5}, Organization = {Department of Neurology, Charit{\'e}, Humboldt-University, 10117 Berlin, Germany. josef.priller\@charite.de}, Pages = {733-8}, Pii = {jcb.200105103}, Pubmed = {11724815}, Title = {Neogenesis of cerebellar Purkinje neurons from gene-marked bone marrow cells in vivo}, Uuid = {F5C87A00-D3AF-11D9-A0E9-000D9346EC2A}, Volume = {155}, Year = {2001}, url = {papers/Priller_JCellBiol2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200105103}} @article{Priller:2006, Abstract = {Prion neuroinvasion is accompanied by maximal activation of microglia, the significance of which for pathogenesis is unknown. Here, we used bone marrow (BM) cells expressing GFP (green fluorescent protein) to study the turnover of microglia in mouse scrapie. We found that >or=50\%of all brain microglia were replaced by BM-derived cells before clinical disease onset. In terminally sick mice, microglia density increased threefold to fourfold. Hence BM-derived microglia rapidly and efficaciously colonize the brain in scrapie. Whereas reconstitution of wild-type mice with prion protein-deficient (Prnp(o/o)) BM did not alter scrapie pathogenesis, Prnp(o/o) mice transplanted with wild-type BM cells were resistant to peripherally administered prions despite high levels of infectivity in the spleen. Cerebellar homogenates from prion-inoculated Prnp(o/o) mice reconstituted with >10\%of wild-type microglia failed to infect transgenic mice overexpressing the cellular prion protein. Hence, in contrast to previous reports, microglia are not competent for efficient prion transport and replication in vivo.}, Author = {Priller, Josef and Prinz, Marco and Heikenwalder, Mathias and Zeller, Nicolas and Schwarz, Petra and Heppner, Frank L. and Aguzzi, Adriano}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Animals;RNA;Cells, Cultured;comparative study;Bone Marrow Transplantation;Microglia;Cell Count;Mice, Inbred C57BL;Green Fluorescent Proteins;research support, non-u.s. gov't;Reverse Transcriptase Polymerase Chain Reaction;Infection;Bone Marrow Cells;Animals, Newborn;Mice, Knockout;Blotting, Western;Flow Cytometry;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Immunohistochemistry;Prions;Gene Expression;Scrapie;Cytokines}, Month = {11}, Nlm_Id = {8102140}, Number = {45}, Organization = {Institute of Neuropathology, Department of Pathology, University of Zurich, 8091 Zurich, Switzerland. josef.priller\@charite.de}, Pages = {11753-62}, Pii = {26/45/11753}, Pubmed = {17093096}, Title = {Early and rapid engraftment of bone marrow-derived microglia in scrapie}, Uuid = {2CD045DC-D693-4240-9E0F-C0CAA1DF3BC1}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2275-06.2006}} @article{Priller:2001a, Abstract = {Gene therapy in the central nervous system (CNS) is hindered by the presence of the blood-brain barrier, which restricts access of serum constituents and peripheral cells to the brain parenchyma. Expression of exogenously administered genes in the CNS has been achieved in vivo using highly invasive routes, or ex vivo relying on the direct implantation of genetically modified cells into the brain. Here we provide evidence for a novel, noninvasive approach for targeting potential therapeutic factors to the CNS. Genetically-modified hematopoietic cells enter the CNS and differentiate into microglia after bone-marrow transplantation. Up to a quarter of the regional microglial population is donor-derived by four months after transplantation. Microglial engraftment is enhanced by neuropathology, and gene-modified myeloid cells are specifically attracted to the sites of neuronal damage. Thus, microglia may serve as vehicles for gene delivery to the nervous system.}, Author = {Priller, J. and Fl{\"u}gel, A. and Wehner, T. and Boentert, M. and Haas, C. A. and Prinz, M. and Fern{\'a}ndez-Klett, F. and Prass, K. and Bechmann, I. and de Boer, B. A. and Frotscher, M. and Kreutzberg, G. W. and Persons, D. A. and Dirnagl, U.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {Cell Differentiation;Animals;Gene Targeting;Bone Marrow Transplantation;Recombinant Proteins;Microglia;Mice, Inbred C57BL;11 Glia;Retroviridae;Green Fluorescent Proteins;Blood-Brain Barrier;Male;Genetic Vectors;Bone Marrow Cells;Gene Therapy;Brain Ischemia;Mice;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {21583810}, Month = {12}, Nlm_Id = {9502015}, Number = {12}, Organization = {Department of Neurology, Charit{\'e}, Humboldt-University, Berlin, Germany. josef.priller\@charite.de}, Pages = {1356-61}, Pii = {nm1201-1356}, Pubmed = {11726978}, Title = {Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment}, Uuid = {558E1B51-A8C6-41C9-B9C1-9442F577B0B9}, Volume = {7}, Year = {2001}, url = {papers/Priller_NatMed2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nm1201-1356}} @article{Prince:1997, Abstract = {Several lines of evidence have suggested that decreases in postsynaptic inhibition may have a role in epileptogenesis in cortical structures. However, other studies have suggested that GABAergic inhibition is spared, or even augmented in some forms of post-lesional epilepsy. In the studies described here, inhibitory events were recorded in two models of post-lesional chronic epileptogenesis. (i) As previously reported (D.A. Prince and G.-F. Tseng. J. Neurophysiol. 69: 1276-1291. 1993), epileptiform activity develops in slices from partially isolated rat neocortical islands 2-3 weeks after the initial in vivo lesion. In this model of post-traumatic epilepsy, large amplitude polyphasic inhibitory postsynaptic currents (IPSCs) in layer V pyramidal neurons are associated with each interictal epileptiform field potential. The frequency of spontaneous IPSCs as well as miniature IPSCs was significantly increased in neocortical slices from the epileptogenic chronically injured cortex versus controls. Immunocytochemical reactions for parvalbumin and calbindin, calcium binding proteins present in subgroups of GABAergic neurons, showed an increased staining of both neuropil and somata within the epileptogenic tissue. Immunoreactivity for glutamic acid decarboxylase (GAD) and GABA also appeared to be increased in the neuropil. (ii) Cortical microgyri resembling human malformations were produced by freeze lesions made transcranially in P0 rat cortex (K.M. Jacobs, M.J. Gutnick, and D.A. Prince. Cereb. Cortex, 6: 514-523. 1996). The boundary between the four-layered microgyrus and surrounding cortex become epileptogenic within about 2 weeks, as judged by evoked extracellular field potentials and cellular activities. Epileptogenesis in the surrounding cortex is not altered when the microgyrus itself is isolated by transcortical cuts. Patch-clamp recordings from layer V neurons in the epileptogenic zone showed that spontaneous IPSCs are larger and more dependent on glutamatergic synapses than in control neurons. The amplitudes of polysynaptic IPSCs evoked by threshold stimulation were also larger than in control cells. Although evaluation of inhibitory events in these models is still incomplete, results to date suggest that GABAergic inhibition may be enhanced in epileptogenic areas associated with chronic cortical injury. Sprouting of axonal arborizations of pyramidal cells onto interneurons, upregulation of GABAergic neurons, and perhaps sprouting of inhibitory axons that make increased numbers of contacts onto pyramidal cells may all contribute to the increased inhibitory drive. Results in these models do not support the disinhibitory hypothesis of chronic epileptogenesis.}, Author = {Prince, D. A. and Jacobs, K. M. and Salin, P. A. and Hoffman, S. and Parada, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0008-4212}, Journal = {Can J Physiol Pharmacol}, Keywords = {21 Epilepsy;Epilepsies, Partial;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Pyramidal Cells;Research Support, U.S. Gov't, P.H.S.;Neural Inhibition;gamma-Aminobutyric Acid;Animals;Humans;Cerebral Cortex;Epilepsy, Post-Traumatic;24 Pubmed search results 2008}, Medline = {97393960}, Month = {5}, Nlm_Id = {0372712}, Number = {5}, Organization = {Stanford University School of Medicine, Department of Neurology and Neurological Sciences, CA 94305-5300, USA.}, Pages = {500-7}, Pubmed = {9250384}, Title = {Chronic focal neocortical epileptogenesis: does disinhibition play a role?}, Uuid = {77C29702-A916-4A10-B942-A552B4176500}, Volume = {75}, Year = {1997}} @article{Prince:1998, Abstract = {Although drug-induced disinhibition is a potent method for producing acute epileptogenesis, data with respect to possible disorders of GABAergic inhibitory function in models of chronic epilepsy are incomplete and inconsistent. We examined rat models of cortical post-traumatic epilepsy, and epileptogenic cortical microgyri. Results suggest enhanced rather than decreased inhibitory function in cortical networks in these preparations. In brain slices from epileptogenic chronically isolated cortex, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature (m)IPSCs in layer V pyramidal neurons is increased compared to control. In the epileptogenic zone adjacent to the microgyrus, both spontaneous and stimulus-induced IPSCs are larger in amplitude than control, and the frequency of sIPSCs is more dependent upon glutamatergic excitation of interneurons than in control layer V neurons of homotopic cortex. Immunocytochemical studies show that there is enhanced immunoreactivity for several proteins in GABAergic interneurons of chronic cortical isolations, and suggest that there may be sprouting of GABAergic axons in the area of injury. This conclusion is supported by anatomic data showing an approximate doubling of the number of presumed inhibitory synapses on somata of layer V pyramidal neurons. These anatomic findings are consistent with the increased frequency of mIPSCs on these neurons. Inhibition is robust in both of these chronic models of epileptogenesis. Increased inhibitory electrogenesis might be pictured as part of the epileptogenic process, e.g. a mechanism for synchronizing the discharge of pyramidal neurons, or as a compensatory mechanism that might prevent the development of abnormal activities in some cases, or limit the intensity of epileptogenesis in others.}, Author = {Prince, D. A. and Jacobs, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:54 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Animals;In Vitro;Evoked Potentials;Rats;Synaptic Transmission;Patch-Clamp Techniques;21 Epilepsy;Epilepsy;Pyramidal Cells;Calcium-Binding Protein, Vitamin D-Dependent;Disease Models, Animal;Brain Injuries;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Freezing;21 Neurophysiology;Parvalbumins;Neurons;24 Pubmed search results 2008;Immunohistochemistry;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {98432478}, Month = {9}, Nlm_Id = {8703089}, Number = {1-2}, Organization = {Department of Neurology and Neurological Sciences, Stanford University School of Medicine, CA 94305-5122, USA. daprince\@leland.stanford.edu}, Pages = {83-92}, Pubmed = {9761311}, Title = {Inhibitory function in two models of chronic epileptogenesis}, Uuid = {A8B29C1A-516B-400C-A27E-7BDE61F25A3D}, Volume = {32}, Year = {1998}, url = {papers/Prince_EpilepsyRes1998.pdf}} @article{Probst:2001, Abstract = {A number of pathological changes have been reported in relation to CA1 pyramidal cells in Alzheimer's disease (AD), among them hyperphosphorylation of tau protein followed by the formation of filamentous tau lesions, granulovacuolar degeneration (GVD), Hirano bodies and spindle-shaped dilatations of distal apical dendrites. Juxtacellular clusters of glutamate receptor (GluR)-positive granules around pyramidal cells of the CA1 sector have been recently reported under the term "non-plaque dystrophic dendrites". We independently found that CA1 pyramidal cells in AD patients are regularly surrounded by ubiquitin-positive granules measuring 1-4 microns in diameter, which we have termed perisomatic granules (PSG). Using confocal microscopy, ubiquitin- and GluR-reactive granules were found to largely coincide and to correspond to the same structure. By immunoelectron microscopy PSG were found to consist of GluR1-2-reactive enlarged synaptic boutons containing tubulo-filamentous or floccular material. PSG were found to be consistently associated with pyramidal (principal) cells but not with interneurons of the CA1 sector. Dual-labeling experiments have shown that PSG are preferentially associated with tau-immunoreactive "pretangle" neurons but not with cells containing filamentous tau inclusions or with tau-negative nerve cell bodies. The number of PSG was found to increase with the severity of AD changes with almost no PSG found in Braak stages I and II and few in stage III. Furthermore, PSG were not AD specific, as shown by their presence around CA1 pyramidal cells in Pick's disease. The reasons for GluR reactivity and ubiquitin complex formation in enlarged perisomatic boutons are unclear. Marked changes in GluR subunits have been observed in association with even moderate AD pathology in hippocampal pyramidal cells in AD and our findings suggest a pathogenic link between PSG and early tau pathology in CA1 neurons. PSG might represent residual and abnormally clustered GluR subunits in degenerating perisomatic neurites. Our work confirms and extend previous study on perisomatic "non-plaque dystrophic dendrites" in AD and establish PSG as a pathological entity distinct from GVD. In addition PSG should be acknowledged among main histological changes associated with hippocampal neurons in AD and Pick's disease.}, Author = {Probst, A. and Herzig, M. C. and Mistl, C. and Ipsen, S. and Tolnay, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Human;Receptors, Glutamate;Vacuoles;Cytoplasm;Female;Cytoplasmic Granules;Extracellular Space;Hippocampus;Pick Disease of the Brain;Not relevant;11 Glia;Ubiquitin;Male;Dendrites;Aged;Neuropil;Alzheimer Disease;Aged, 80 and over;Immunohistochemistry;Microscopy, Electron;Cell Death}, Medline = {21604277}, Month = {12}, Nlm_Id = {0412041}, Number = {6}, Organization = {Institute of Pathology, Division of Neuropathology, University of Basel, Sch{\"o}nbeinstrasse 40, CH-4003 Basel, Switzerland. aprobst\@uhbs.ch}, Pages = {636-44}, Pubmed = {11761725}, Title = {Perisomatic granules (non-plaque dystrophic dendrites) of hippocampal CA1 neurons in Alzheimer's disease and Pick's disease: a lesion distinct from granulovacuolar degeneration}, Uuid = {B48B34B5-E2C3-4B4F-B6A2-620E8CBCACB4}, Volume = {102}, Year = {2001}} @article{Proctor:2005, Abstract = {We showed previously that loss of the integrin beta8 subunit, which forms alphavbeta8 heterodimers, results in abnormal vascular development in the yolk sac, placenta, and brain. Animals lacking the integrin beta8 (itgbeta8) gene die either at midgestation, because of insufficient vascularization of the placenta and yolk sac, or shortly after birth with severe intracerebral hemorrhage. To specifically focus on the role of integrins containing the beta8 subunit in the brain, and to avoid early lethalities, we used a targeted deletion strategy to delete itgbeta8 only from cell types within the brain. Ablating itgbeta8 from vascular endothelial cells or from migrating neurons did not result in cerebral hemorrhage. Targeted deletion of itgbeta8 from the neuroepithelium, however, resulted in bilateral hemorrhage at postnatal day 0, although the phenotype was less severe than in itgbeta8-null animals. Newborn mice lacking itgbeta8 from the neuroepithelium had hemorrhages in the cortex, ganglionic eminence, and thalamus, as well as abnormal vascular morphogenesis, and disorganized glia. Interestingly, adult mice lacking itgbeta8 from cells derived from the neuroepithelium did not show signs of hemorrhage. We propose that defective association between vascular endothelial cells and glia lacking itgbeta8 is responsible for the leaky vasculature seen during development but that an unidentified compensatory mechanism repairs the vasculature after birth.}, Author = {Proctor, John M. and Zang, Keling and Wang, Denan and Wang, Rong and Reichardt, Louis F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development}, Month = {10}, Nlm_Id = {8102140}, Number = {43}, Organization = {Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, California 94143, USA.}, Pages = {9940-8}, Pii = {25/43/9940}, Pubmed = {16251442}, Title = {Vascular development of the brain requires beta8 integrin expression in the neuroepithelium}, Uuid = {20614251-EE89-40AC-9F98-569B90B9E7E2}, Volume = {25}, Year = {2005}, url = {papers/Proctor_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3467-05.2005}} @article{Puig:2002, Abstract = {To investigate to what extent myeloablation, graft size, and ex vivo manipulation influence the engraftment and long-term survival of transduced murine hematopoietic cells, groups of C57BL/6J (CD45.2) mice receiving total body irradiation (TBI) (1-9 Gy) or no irradiation were transplanted with either transduced bone marrow (BM) cells, at two cell doses, or with fresh BM cells from B6/SJL (CD45.1) congenic mice. Short (40 days) and long-term (5 months) engraftment and transgene expression were measured by FACS analysis. No donor cells were detected in the hematopoietic tissues of non-myeloablated mice, whereas in the irradiated animals, levels of engraftment correlated well with the dose of TBI administered. Similar percentages of transgene-expressing cells were found in the grafted hematopoietic cells of all groups of mice, regardless of the dose of TBI administered or the level of engraftment achieved. This suggests that the engrafted animals could become tolerant to the transgene product (enhanced green fluorescent protein, EGFP). Our results indicate that TBI facilitates the engraftment of manipulated hematopoietic cells in a dose-dependent manner, that mice engrafted with EGFP(+) hematopoietic cells probably acquire tolerance to EGFP, and that increasing the graft size and reducing the ex vivo manipulation required for retroviral gene transfer of hematopoietic cells also enhances their engrafting potential.}, Author = {Puig, T. and K{\'a}d{\'a}r, E. and Lim{\'o}n, A. and Cancelas, J. A. and Eixarch, H. and Luqu{\'\i}n, L. and Garc{\'\i}a, M. and Barquinero, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Transduction, Genetic;Animals;Regression Analysis;Female;Mice, Inbred C57BL;Retroviridae;11 Glia;Time Factors;Hematopoietic Stem Cell Transplantation;Green Fluorescent Proteins;Genetic Vectors;Gene Therapy;Flow Cytometry;Mice;Transplantation Conditioning;Luminescent Proteins;Stem Cells;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {22265327}, Month = {11}, Nlm_Id = {9421525}, Number = {21}, Organization = {Facultat de Biologia, Universitat de Girona, Spain.}, Pages = {1472-9}, Pubmed = {12378410}, Title = {Myeloablation enhances engraftment of transduced murine hematopoietic cells, but does not influence long-term expression of the transgene}, Uuid = {F1476AC4-2406-405F-90BD-8B94311CE37F}, Volume = {9}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3301826}} @article{Pukrop:2006, Abstract = {Interactions between neoplastic and stromal cells contribute to tumor progression. Wnt genes, involved in cell migration and often deregulated in cancers, are attractive candidates to regulate these effects. We have recently shown that coculture of breast cancer cells with macrophages enhances invasiveness via matrix metalloproteases and TNF-alpha. Here we demonstrate that coculture of MCF-7 cells and macrophages leads to up-regulation of Wnt 5a in the latter. This was accompanied by activation of AP-1/c-Jun in MCF-7. Recombinant Wnt 5a mimicked the coculture effect. Wnt 5a was also detectable in tumor-associated macrophages in primary breast cancers. Experiments with agonists and antagonists of Wnt signaling revealed that a functional canonical pathway in the tumor cells was a necessary prerequisite; however, noncanonical signaling via Wnt 5a and the Jun-N-terminal kinase pathway was critical for invasiveness. It was also responsible for induction of matrix metalloprotease-7, known to release TNF-alpha. All these effects could be antagonized by dickkopf-1. Our results indicate that Wnt 5a is essential for macrophage-induced invasiveness, because it regulates tumor cell migration as well as proteolytic activity of the macrophages. The function of Wnt 5a as either a suppressor or promoter of malignant progression seems to be modulated by intercellular interactions. Wnt 5a detection in tumor-associated macrophages in breast cancer biopsies supports the assumption that similar events play a role in vivo.}, Author = {Pukrop, T. and Klemm, F. and Hagemann, Th and Gradl, D. and Schulz, M. and Siemes, S. and Tr{\"u}mper, L. and Binder, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {7505876}, Number = {14}, Organization = {*Department of Haematology/Oncology, Georg-August University, 37099 G{\"o}ttingen, Germany.}, Pages = {5454-9}, Pii = {0509703103}, Pubmed = {16569699}, Title = {Wnt 5a signaling is critical for macrophage-induced invasion of breast cancer cell lines}, Uuid = {FC3CBFB7-8CAC-48FA-BD35-D3BFDE59347A}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0509703103}} @article{Pumiglia:2006, Author = {Pumiglia, Kevin and Temple, Sally}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Humans;24 Pubmed search results 2008;Cell Differentiation;Serpins;Eye Proteins;Neuronal Plasticity;Stem Cells;Angiogenesis Inhibitors;comment;Blood Vessels;Animals;Brain;Brain Neoplasms;Nerve Growth Factors;news}, Month = {3}, Nlm_Id = {9809671}, Number = {3}, Pages = {299-300}, Pii = {nn0306-299}, Pubmed = {16498420}, Title = {PEDF: bridging neurovascular interactions in the stem cell niche}, Uuid = {30803BB7-A690-4ED4-96A7-71875107155D}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0306-299}} @article{Puopolo:1998, Abstract = {The periglomerular cells of the rat olfactory bulb, a virtually unknown population of interneurons, have been studied applying the whole-cell patch-clamp technique to thin slices. A prominent result, obtained under current-clamp conditions, is that these cells appear to be functionally heterogeneous, and show distinct excitability profiles. Voltage-clamp analysis allows the identification of the ionic basis of these differences and suggests a division into at least two classes, based on the characteristics of the K+ conductances. The first group displays two K+ conductances (delayed rectifier, gKV, and fast transient, gA) of similar amplitude, and under current-clamp conditions shows the usual outward rectifying behaviour at depolarized potentials. The second group has a large gA, and a small or absent gKV. Consequently, following sustained depolarizations under current-clamp conditions leading to inactivation of gA, these neurons do not show any sign of outward rectification and behave as ohmic elements, as normally observed only at hyperpolarized potentials. The transition ion zinc (10-300 microM) affects gA but not gKV The inactivation process (steady-state curve and rate constant) is strongly altered by Zn2+, the activation process less so; open-channel conductance is not affected. The Zn2+ effect is unlikely to be due to surface charge screening or to a mechanism involving channel block. In view of the substantial presence of zinc ions in the olfactory nerve terminals, its actions on the A-current could be of some relevance for physiological function.}, Author = {Puopolo, M. and Belluzzi, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Kinetics;Zinc;Rats;Rats, Wistar;Tetrodotoxin;Olfactory Bulb;Solutions;Electrophysiology;Patch-Clamp Techniques;Potassium Channels;Membrane Potentials;Animals}, Medline = {98424097}, Month = {3}, Nlm_Id = {8918110}, Number = {3}, Organization = {Dipartimento di Biologia, Universit\`{a} di Ferrara, Italy.}, Pages = {1073-83}, Pubmed = {9753175}, Title = {Functional heterogeneity of periglomerular cells in the rat olfactory bulb}, Uuid = {FBEBF819-D067-11DA-8A8C-000D9346EC2A}, Volume = {10}, Year = {1998}} @article{Puopolo:2001, Abstract = {Spontaneous, low-frequency voltage oscillations (LFOs) were observed in the neurons of rat olfactory bulb upon disinhibition with GABAA antagonists and/or removal of Mg2+ from external saline. Ordinarily, LFOs presented a highly organized temporal structure, with bursts recurring regularly at about 0.05 Hz. Slow depolarizing shifts with similar frequencies were observed in all types of bulbar neurons. Simultaneous recordings from mutually independent neurons showed that LFOs were highly synchronized in distinct cells. The occurrence of LFOs was prevented by NMDA, but not AMPA/kainate, receptor antagonists. The oscillations were also halted by Ca2+ antagonists and tetrodotoxin. The pace of the oscillations was reset by stimulation of the olfactory nerve but not by direct injection of depolarizing current into the oscillating cell. Removal of the outer portion of the slice with a cut along the external plexiform layer provided crucial evidence that the bursting activity first initiated in the glomerular region and propagated synaptically downstream towards the inner layers, suggesting an organizing role for olfactory glomeruli.}, Author = {Puopolo, M. and Belluzzi, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Eur J Neurosci}, Keywords = {Neurons/*drug effects/*physiology;I;GABA Antagonists/*pharmacology;N-Methylaspartate/*physiology;Rats;Rats, Wistar;Oscillometry;Animal;In Vitro;Bicuculline/*pharmacology;Support, Non-U.S. Gov't;Olfactory Bulb/cytology/*drug effects/*physiology;13 Olfactory bulb anatomy;Nerve Net/*physiology;Magnesium/*pharmacology}, Number = {1}, Organization = {Dipartimento di Scienze Biomediche &Terapie Avanzate, Sezione di Fisiologia Umana, Universita di Ferrara, Via Fossato di Mortara 17/19 44100 Ferrara, Italy.}, Pages = {92-102.}, Title = {NMDA-dependent, network-driven oscillatory activity induced by bicuculline or removal of Mg2+ in rat olfactory bulb neurons}, Uuid = {E6C81ED9-6AB5-4F33-8BFA-81440E905C71}, Volume = {13}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11135007}} @article{Puopolo:2005, Abstract = {We examined the electrophysiological properties of a population of identified dopaminergic periglomerular cells of the main olfactory bulb, using transgenic mice in which catecholaminergic neurons expressed human placental alkaline phosphatase (PLAP) on the outer surface of the plasma membrane. After acute dissociation, living dopaminergic periglomerular cells were identified by a fluorescently labeled monoclonal antibody to PLAP. In current clamp mode, dopaminergic periglomerular cells spontaneously generated action potentials in a rhythmic fashion, with an average frequency of 8 Hz. The hyperpolarization-activated cation current (Ih) did not seem important for pacemaking, since blocking the current with ZD 7288 or Cs(+) had little effect on spontaneous firing. To investigate what ionic currents do drive pacemaking, we performed action potential clamp experiments using records of pacemaking as voltage command in voltage clamp experiments. We found that substantial TTX-sensitive Na(+) current flows during the interspike depolarization. In addition, substantial Ca(2+) current flowed during the interspike interval, and blocking Ca(2+) current hyperpolarized the neurons and stopped spontaneous firing. These results show that dopaminergic periglomerular cells have intrinsic pacemaking activity, supporting the possibility that they can maintain a tonic release of dopamine to modulate the sensitivity of the olfactory system during odor detection. Calcium entry into these neurons provides electrical drive for pacemaking as well as triggering transmitter release.}, Author = {Puopolo, and Bean, and Raviola,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {0375404}, Pii = {00225.2005}, Pubmed = {16033943}, Title = {Spontaneous Activity of Isolated Dopaminergic Periglomerular Cells of the Main Olfactory Bulb}, Uuid = {A08CF7BE-A4DD-4883-8B52-BB5C40CCE8E2}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00225.2005}} @article{Puopolo:1996, Abstract = {The capacity of periglomerular cells (PGc) to give fast, Na-dependent action potentials is a crucial and debated issue for the comprehension of how sensory information is processed in the olfactory bulb (OB). Using patchclamp whole cell recording in thin slices of rat OB (P8-P20) we showed that fast sodium conductance is present in all the PGc studied, that this current is sufficiently large to generate action potentials and that action potentials can be evoked in these cells by direct stimulation of the olfactory nerve. A comprehensive kinetic characterization of INa is also presented.}, Author = {Puopolo, M. and Belluzzi, O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Research Support, Non-U.S. Gov't;Rats;Sodium Channels;Rats, Wistar;In Vitro;Olfactory Bulb;Interneurons;Animals;Patch-Clamp Techniques;13 Olfactory bulb anatomy}, Medline = {97061648}, Month = {7}, Nlm_Id = {9100935}, Number = {11}, Organization = {Dipartimento di Biologia, Universit\`{a} di Ferrara, Italy.}, Pages = {1846-50}, Pubmed = {8905678}, Title = {Sodium current in periglomerular cells of rat olfactory bulb in vitro}, Uuid = {FBEBFEF0-D067-11DA-8A8C-000D9346EC2A}, Volume = {7}, Year = {1996}} @article{Puri:1988, Abstract = {Fusion of vesicular stomatitis virus (VSV) with Vero cells was measured after exposure of the virus to low pH under a variety of experimental conditions. The method of relief of fluorescence self-quenching of the probe octadecylrhodamine was used to monitor fusion. Incubation of the virus at pH 5.5 prior to binding to cells led to significant enhancement of fusion at the plasma membrane, whereas fusion via the endocytic pathway was inhibited. Fusion of pH 5.5-pretreated VSV showed a similar pH threshold for fusion as nontreated virus, and it was blocked by antibody to VSV G protein. Activation of VSV by pretreatment at low pH was only slightly dependent on temperature. In contrast, when VSV was first bound to target cells and subsequently exposed at 4 degrees C to the low pH, activation of the fusion process did not occur. The pH 5.5-mediated activation of VSV could be reversed by returning the pH to neutral in the absence of target membranes. The low pH pretreatment also led to aggregation of virus; large aggregates could be pelleted by low speed centrifugation and only the effects of the supernatant, which consist of single virions and/or microaggregates, were considered. The data were analyzed in the framework of an allosteric model according to which viral spike glycoproteins undergo a pH-dependent conformational transition to an active (fusion-competent) state. Based on that analysis we conclude that the conformational transition to the active state is rate-limiting for fusion and that the viral spike glycoproteins are fusion-competent only in their protonated form.}, Author = {Puri, A. and Winick, J. and Lowy, R. J. and Covell, D. and Eidelman, O. and Walter, A. and Blumenthal, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {Vero Cells;Allosteric Regulation;Kinetics;Cell Line;Receptors, Virus;Thermodynamics;Models, Theoretical;Vesicular stomatitis-Indiana virus;delete_this;Animals;Hydrogen-Ion Concentration;Virus Activation;15 Retrovirus mechanism}, Medline = {88169591}, Month = {4}, Nlm_Id = {2985121R}, Number = {10}, Organization = {Section on Membrane Structure and Function, National Cancer Institute, Bethesda, Maryland 20892.}, Pages = {4749-53}, Pubmed = {2832405}, Title = {Activation of vesicular stomatitis virus fusion with cells by pretreatment at low pH}, Uuid = {7D65DAC8-EE2C-11DA-8605-000D9346EC2A}, Volume = {263}, Year = {1988}, url = {papers/Puri_JBiolChem1988.pdf}} @article{Purpura:1982, Abstract = {Cortical biopsies obtained from 5 young children with severe neurobehavioral retardation of unknown etiology have been analyzed using Golgi and EM techniques. The normally cylindrical geometry of individual dendritic processes of pyramidal and non-pyramidal neurons is interrupted by the formation of distinct varicosities. While over 90\%of observed cells are affected, the extent of varicosity formation varies from cell to cell and is most prominent in medium and small pyramidal cells. Varicosities may occur in the periphery only, or they may extend proximally to primary dendritic trunks. Accompanying changes include thin and irregular proximal processes, loss of dendritic spines, and predominance of long, thin tortuous spines. Ultrastructural analysis reveals characteristic changes in the cytoskeleton of these processes. Microtubules, within the larger proximal processes, twist and turn, relative to one another and relative to the long axis of the process. In varicose regions, microtubules course in roughly parallel array through constricted segments, only to splay away from one another on entering an expansion. Synapses are evident on constricted and expanded segments, as well as on spines. Alterations in dendritic structure of both pyramidal and non-pyramidal neurons may represent a primary target in the pathobiological process underlying neurobehavioral failure.}, Author = {Purpura, D. P. and Bodick, N. and Suzuki, K. and Rapin, I. and Wurzelmann, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Staining and Labeling;10 Development;Dendrites;Golgi Apparatus;Infant;Microscopy, Electron;Microtubules;Get paper from library;Research Support, U.S. Gov't, P.H.S.;Developmental Disabilities;Female;10 Structural plasticity;Male;Humans;24 Pubmed search results 2008;Cerebral Cortex;case reports}, Medline = {83102362}, Month = {11}, Nlm_Id = {0045503}, Number = {3}, Pages = {287-97}, Pubmed = {6185182}, Title = {Microtubule disarray in cortical dendrites and neurobehavioral failure. I. Golgi and electron microscopic studies}, Uuid = {EBA9C056-89F2-4FA8-AB54-E31B65EE61D7}, Volume = {281}, Year = {1982}} @article{Putz:2005, Abstract = {The balance between proliferation and apoptosis is critical for proper development of the nervous system. Yet, little is known about molecules that regulate apoptosis of proliferative neurons. Here we identify a soluble, secreted form of CPG15 expressed in embryonic rat brain regions undergoing rapid proliferation and apoptosis, and show that it protects cultured cortical neurons from apoptosis by preventing activation of caspase 3. Using a lentivirus-delivered small hairpin RNA, we demonstrate that endogenous CPG15 is essential for the survival of undifferentiated cortical progenitors in vitro and in vivo. We further show that CPG15 overexpression in vivo expands the progenitor pool by preventing apoptosis, resulting in an enlarged, indented cortical plate and cellular heterotopias within the ventricular zone, similar to the phenotypes of mutant mice with supernumerary forebrain progenitors. CPG15 expressed during mammalian forebrain morphogenesis may help balance neuronal number by countering apoptosis in specific neuroblasts subpopulations, thus influencing final brain size and shape.}, Author = {Putz, and Harwell, and Nedivi,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Membrane Proteins;Mice;Embryonic Development;Animals, Newborn;Blotting, Northern;Age Factors;Cell Cycle;Stem Cells;Mice, Transgenic;In Situ Nick-End Labeling;research support, u.s. gov't, p.h.s. ;Apoptosis;Cells, Cultured;Phospholipase C;Cell Membrane;Proto-Oncogene Proteins c-akt;Cell Fractionation;Green Fluorescent Proteins;comparative study ;Bromodeoxyuridine;Rats, Sprague-Dawley;24 Pubmed search results 2008;Cerebral Cortex;21 Neurophysiology;Intermediate Filament Proteins;Male;Proto-Oncogene Proteins;Cloning, Molecular;Food Deprivation;Receptors, Transferrin;Embryo;Histones;Humans;Neurons;Pregnancy;In Situ Hybridization;Neurofilament Proteins;Time Factors;Female;Fluorescent Antibody Technique;RNA, Messenger;RNA, Catalytic;research support, non-u.s. gov't ;Transfection;Gene Expression Regulation, Developmental;Ki-67 Antigen;Analysis of Variance;Animals;Protein-Serine-Threonine Kinases;Cell Count;Blotting, Western;Lentivirus;in vitro ;Nerve Tissue Proteins;Rats}, Month = {2}, Nlm_Id = {9809671}, Number = {3}, Organization = {[1] The Picower Center for Learning and Memory, Departments of Brain and Cognitive Sciences and Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. [2] These authors contributed equally to this work.}, Pages = {322-31}, Pii = {nn1407}, Pubmed = {15711540}, Title = {Soluble CPG15 expressed during early development rescues cortical progenitors from apoptosis}, Uuid = {591AD97E-3F0A-4CEE-9A47-F58CA8E5601E}, Volume = {8}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1407}} @article{Qian:1997, Abstract = {The embryonic cerebral cortex contains a population of stem-like founder cells capable of generating large, mixed clones of neurons and glia in vitro. We report that the default state of early cortical stem cells is neuronal, and that stem cells are heterogeneous in the number of neurons that they generate. In low fibroblast growth factor (FGF2) concentrations, most maintain this specification, generating solely neuronal progeny. Oligodendroglial production within these clones is stimulated by a higher, threshold level of FGF2, and astrocyte production requires additional environmental factors. Because most cortical neurons are born before glia in vivo, these data support a model in which the scheduled production of cortical cells involves an intrinsic neuronal program in the early stem cells and exposure to environmental, glia-inducing signals. 0896-6273 Journal Article}, Author = {Qian, X. and Davis, A. A. and Goderie, S. K. and Temple, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Neuron}, Keywords = {Cell Differentiation/drug effects;Pregnancy;Animals;Cells, Cultured;Embryo and Fetal Development;Cerebral Cortex/cytology/*embryology;Stem Cells/*cytology/drug effects/physiology;Oligodendroglia/cytology/drug effects;Female;Glial Fibrillary Acidic Protein/analysis;Neuroglia/*cytology/drug effects;DNA Primers;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Receptors, Fibroblast Growth Factor/biosynthesis;Mice;Polymerase Chain Reaction;Fibroblast Growth Factor 2/*pharmacology;Clone Cells;Neurons/*cytology/drug effects;C pdf}, Number = {1}, Organization = {Department of Pharmacology and Neuroscience, Albany Medical College, NY 12208, USA.}, Pages = {81-93}, Title = {FGF2 concentration regulates the generation of neurons and glia from multipotent cortical stem cells}, Uuid = {79893BE1-80C7-469E-99E8-EEDE2927FC11}, Volume = {18}, Year = {1997}, url = {papers/Qian_Neuron1997.pdf}} @article{Qiao:2005, Abstract = {BACKGROUND: Excessive production of interleukin (IL)-4, IL-13 and interferon (IFN)-gamma is thought to be important in the development of allergic disease and atopy. Several investigators have linked the IL-4 and IL-4R genes to allergic disease and atopy. The aim of this study is to further explore the mechanism of penicillins allergy and evaluate the possible role of the IL-4 C-589T and IL-4RalphaQ576R polymorphisms in modulating the allergic responses to penicillins. METHODS: Radioallergosorbent test (RAST) was used to detect eight kinds of specific immunoglobulin E (IgE) to penicillins in serum. Serum levels of IL-4, IL-13 and IFN-gamma were measured by using enzyme-linked immunosorbent assay (ELISA). The IL-4 C-589T and IL-4RalphaQ576R polymorphisms were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). RESULTS: Compared with control subjects, there were significantly higher levels of IL-4, IL-13 and IFN-gamma in allergic patients with positive specific IgE (P < 0.01), and the lower levels of IL-4 and IFN-gamma were observed in allergic patients with negative specific IgE (P < 0.05). We found a growing trend of IL-4 and IL-13 levels with the kind increasing of positive specific IgE, and even there were significant correlations between the three kinds of cytokines and many kinds of specific IgE (P < 0.05). The IL-4Ralpha*Q576 allele was significantly increased in patients with penicillins allergy compared with control subjects (P < 0.01). Furthermore, the allele was strongly associated with increased serum-specific benzylpenicilloyl (BPO)-, phenoxomethylpenicillanyl (PVA)- or ampicillanyl (APA)-IgE levels in patients with positive specific IgE (P < 0.05). CONCLUSIONS: These data suggest that IL-4, IL-13 and IFN-gamma play an important roles in penicillins allergy. The IL-4RalphaQ576R polymorphism may involve in the development of penicillins allergy, and through modulating specific serum IgE levels.}, Author = {Qiao, H-L L. and Yang, J. and Zhang, Y-W W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0105-4538}, Journal = {Allergy}, Keywords = {Arginine;Cytokines;Research Support, Non-U.S. Gov't;Humans;Middle Aged;Interleukin-4;Receptors, Cell Surface;Penicillins;Drug Hypersensitivity;Female;Immunoglobulin E;Interferon Type II;Child;14 Immune;Male;Glutamine;Aged;Interleukin-13;Adult;Protein Isoforms;24 Pubmed search results 2008;Adolescent}, Month = {8}, Nlm_Id = {7804028}, Number = {8}, Organization = {Department of Clinical Pharmacology, School of Medicine, Zhengzhou University, Zhengzhou, China.}, Pages = {1053-9}, Pii = {ALL816}, Pubmed = {15969687}, Title = {Relationships between specific serum IgE, cytokines and polymorphisms in the IL-4, IL-4Ralpha in patients with penicillins allergy}, Uuid = {3579DD33-E1BF-4345-A1C3-BFD9096A1961}, Volume = {60}, Year = {2005}, url = {papers/Qiao_Allergy2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1398-9995.2005.00816.x}} @article{Qin:2006, Abstract = {The transcription factor E2F1 is known to regulate cell proliferation and has been thought to modulate tumorigenesis via this mechanism alone. Here we show that mice deficient in E2F1 exhibit enhanced angiogenesis. The proangiogenic phenotype in E2F1 deficiency is the result of overproduction of vascular endothelial growth factor (VEGF) and is prevented by VEGF blockade. Under hypoxic conditions, E2F1 down-regulates the expression of VEGF promoter activity by associating with p53 and specifically down-regulating expression of VEGF but not other hypoxia-inducible genes, suggesting a promoter structure context-dependent regulation mechanism. We found that the minimum VEGF promoter mediating transcriptional repression by E2F1 features an E2F1- binding site with four Sp-1 sites in close proximity. These data disclose an unexpected function of endogenous E2F1: regulation of angiogenic activity via p53-dependent transcriptional control of VEGF expression.}, Author = {Qin, and Kishore, and Dolan, and Silver, and Wecker, and Luedemann, and Thorne, and Hanley, and Curry, and Heyd, and Dinesh, and Kearney, and Martelli, and Murayama, and Goukassian, and Zhu, and Losordo,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7505876}, Number = {29}, Organization = {*Division of Cardiovascular Research, Tufts University School of Medicine, Caritas St. Elizabeths Medical Center, Boston, MA 02135.}, Pages = {11015-11020}, Pii = {0509533103}, Pubmed = {16835303}, Title = {Cell cycle regulator E2F1 modulates angiogenesis via p53-dependent transcriptional control of VEGF}, Uuid = {0FEAF92A-B1D2-4834-A825-4009AA7D639F}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0509533103}} @article{Quesenberry:2005, Author = {Quesenberry, Peter J. and Dooner, Gerri and Dooner, Mark and Abedi, Mehrdad}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {17 Transplant Regeneration;08 Aberrant cell cycle;22 Stem cells}, Month = {5}, Nlm_Id = {0404511}, Number = {5725}, Organization = {Department of Research, The Center for Stem Cell Biology, Providence, RI 02908-4735, USA. pquesenberry\@rwmc.org}, Pages = {1121-2}, Pii = {308/5725/1121}, Pubmed = {15905387}, Title = {Developmental biology: Ignoratio elenchi: red herrings in stem cell research}, Uuid = {4CE79725-0EF4-45D8-9A03-D290E60A307D}, Volume = {308}, Year = {2005}, url = {papers/Quesenberry_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1104432}} @article{Quinn:1995, Abstract = {Fluorescent neuroanatomic techniques, such as immunofluorescence and retrograde and anterograde tracing studies, derive great utility from their specificity. However, the specificity can be a drawback as well, in that it may be difficult to assess labeled neurons or neural processes in their cytoarchitectonic context. We report the characteristics of a newly synthesized fluorescent counterstain, Fluoro Nissl Green (3,8-diamino-10H-quindoline) with spectral characteristics similar to fluorescein. This Nissl-like counterstain can be used as a green neuronal counterstain for red-emitting markers such as rhodamine and Di-I. 0304-3940 Journal Article}, Author = {Quinn, B. and Toga, A. W. and Motamed, S. and Merlic, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:56 -0400}, Journal = {Neurosci Lett}, Keywords = {*Quinolines;Rats;T pdf;*Alkaloids;Neurons/*cytology;*Fluorescent Dyes;*Indoles;Support, Non-U.S. Gov't;Animals;Male;23 Technique}, Number = {3}, Organization = {Department of Neurology, University of California, Los Angeles 90024, USA.}, Pages = {169-72}, Title = {Fluoro nissl green: a novel fluorescent counterstain for neuroanatomy}, Uuid = {95B1ED7A-FC6A-48B7-A297-7F521C957188}, Volume = {184}, Year = {1995}, url = {papers/Quinn_NeurosciLett1995.pdf}} @article{Quintana:2006, Abstract = {Transient anoxia/hypoglycaemia in organotypic hippocampal slice cultures, a model of transient brain ischaemia, ultimately results in delayed cell death. Although the mechanisms underlying this delayed death remain unknown, an increase in excitatory drive has been postulated. We report here that transient anoxia/hypoglycaemia in rat hippocampal slice cultures resulted in a 70-80\%enhancement of evoked, alpha-amino-3-hydroxy-5-methyl-4-isoxazolpropionic acid (AMPA) receptor-mediated, excitatory responses lasting over 60 min. This effect was prevented by blockade of N-methyl-d-aspartate (NMDA) receptors, did not involve changes of paired-pulse facilitation ratio, but was associated with a 50\%increase in amplitude, but not frequency, of spontaneous miniature excitatory postsynaptic currents (mEPSCs). Consistent with this, paired recordings revealed the appearance of AMPA receptor-mediated EPSCs at previously silent synapses and occlusion by prior induction of long-term potentiation (LTP). Transient anoxia/hypoglycaemia further resulted in a 63\%potentiation of evoked NMDA receptor-dependent synaptic responses, accounting for the 20\%increase in ratio of AMPA to NMDA responses. No change in rectification properties of AMPA receptor-mediated currents could be detected within the first hour following anoxia/hypoglycaemia-induced potentiation. Western blot analyses of slice cultures exposed to either control conditions or a short anoxia/hypoglycaemia revealed a marked, 50-70\%increase of GluR1, GluR2/3 and NR1 subunits 1 h, but not 15 min, after the anoxic/hypoglycaemic episode. This increase was blocked by an inhibitor of protein synthesis. Together these results indicate that a transient anoxia/hypoglycaemia is associated with a marked enhancement of excitatory transmission sharing similarities with the mechanisms underlying LTP, and is correlated with an increased synthesis of excitatory receptor subunits.}, Author = {Quintana, Patrice and Alberi, Stefano and Hakkoum, David and Muller, Dominique}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Receptors, Glutamate;Electric Stimulation;Animals;Hypoglycemia;Gene Expression Regulation;Rats;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Patch-Clamp Techniques;Excitatory Amino Acid Agonists;in vitro ;Hippocampus;comparative study ;Anoxia;Time Factors;research support, non-u.s. gov't ;Animals, Newborn;Blotting, Western;21 Neurophysiology;N-Methylaspartate;24 Pubmed search results 2008;Dose-Response Relationship, Radiation;Excitatory Postsynaptic Potentials}, Month = {2}, Nlm_Id = {8918110}, Number = {4}, Organization = {Department of Basic Neurosciences, University of Geneva, 1211 Geneva 4, Switzerland.}, Pages = {975-83}, Pii = {EJN4617}, Pubmed = {16519662}, Title = {Glutamate receptor changes associated with transient anoxia/hypoglycaemia in hippocampal slice cultures}, Uuid = {B803B4DF-A797-4A11-840B-A4A24E91AA69}, Volume = {23}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.04617.x}} @article{Quiroga:2005, Abstract = {It takes a fraction of a second to recognize a person or an object even when seen under strikingly different conditions. How such a robust, high-level representation is achieved by neurons in the human brain is still unclear. In monkeys, neurons in the upper stages of the ventral visual pathway respond to complex images such as faces and objects and show some degree of invariance to metric properties such as the stimulus size, position and viewing angle. We have previously shown that neurons in the human medial temporal lobe (MTL) fire selectively to images of faces, animals, objects or scenes. Here we report on a remarkable subset of MTL neurons that are selectively activated by strikingly different pictures of given individuals, landmarks or objects and in some cases even by letter strings with their names. These results suggest an invariant, sparse and explicit code, which might be important in the transformation of complex visual percepts into long-term and more abstract memories.}, Author = {Quiroga, R. Quian and Reddy, L. and Kreiman, G. and Koch, C. and Fried, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Humans;Memory;Face;Middle Aged;Brain;Female;Hippocampus;research support, non-u.s. gov't;Male;Substrate Specificity;ROC Curve;research support, u.s. gov't, p.h.s.;Neurons;21 Neurophysiology;Adult;research support, n.i.h., extramural;Pattern Recognition, Visual;Temporal Lobe;24 Pubmed search results 2008;research support, u.s. gov't, non-p.h.s.;Models, Neurological;Adolescent}, Month = {6}, Nlm_Id = {0410462}, Number = {7045}, Organization = {Computation and Neural Systems, California Institute of Technology, Pasadena, California 91125, USA.}, Pages = {1102-7}, Pii = {nature03687}, Pubmed = {15973409}, Title = {Invariant visual representation by single neurons in the human brain}, Uuid = {4A301E0C-E9E9-41D0-AFF2-355760612803}, Volume = {435}, Year = {2005}, url = {papers/Quiroga_Nature2005.pdf}, Bdsk-File-2 = {papers/Quiroga_Nature2005a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03687}} @article{Raballo:2000, Abstract = {Little is known about regionally specific signals that control the number of neuronal progenitor cells in vivo. We have previously shown that the germline mutation of the basic fibroblast growth factor (Fgf2) gene results in a reduction in the number of cortical neurons in the adult. We show here that Fgf2 is expressed in the pseudostratified ventricular epithelium (PVE) in a dorsoventral gradient and that Fgf2 and its receptor, Fgfr-1, are downregulated by mid to late stages of neurogenesis. In Fgf2 knockout mice, the volume and cell number of the dorsal PVE (the cerebral cortical anlage) are substantially smaller, whereas the volume of the basal PVE is unchanged. The dorsal PVE of Fgf2 knockout mice has a 50\%decrease in founder cells and a reduced expansion of the progenitor pool over the first portion of neurogenesis. Despite this reduction, the degree of apoptosis within the PVE is not changed in the Fgf2 knockouts. Cortical neuron number was decreased by 45\%in Fgf2 knockout mice by the end of neurogenesis, whereas the number of neurons in the basal ganglia was unaffected. Microscopically, the frontal cerebral cortex of neonatal Fgf2 null mutant mice lacked large neurons in deep cortical layers. We suggest that Fgf2 is required for the generation of a specific class of cortical neurons arising from the dorsal PVE.}, Author = {Raballo, R. and Rhee, J. and Lyn-Cook, R. and Leckman, J. F. and Schwartz, M. L. and Vaccarino, F. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {J Neurosci}, Keywords = {C-16;*Gene Expression Regulation, Developmental;Apoptosis;Animal;Telencephalon/*embryology;Choroid Plexus/embryology;Receptors, Fibroblast Growth Factor/genetics/*physiology;Prosencephalon/embryology;Receptor Protein-Tyrosine Kinases/genetics/*physiology;Mice, Knockout;04 Adult neurogenesis factors;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Germ-Line Mutation;Gestational Age;Cerebral Cortex/*embryology;Fibroblast Growth Factor, Basic/deficiency/genetics/*physiology;Fetal Development}, Number = {13}, Organization = {Child Study Center and Section of Neurobiology, Yale University, New Haven, Connecticut 06520, USA.}, Pages = {5012-23.}, Title = {Basic fibroblast growth factor (Fgf2) is necessary for cell proliferation and neurogenesis in the developing cerebral cortex}, Uuid = {862E996C-1FD9-4AFE-999F-B319BAFCE050}, Volume = {20}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10864959}} @article{Rabchevsky:2000, Abstract = {We have recently demonstrated that following a moderate contusion spinal cord injury (SCI) to rats, subsequent administration of basic fibroblast growth factor (bFGF) significantly enhances functional recovery and tissue sparing. To further characterize the effects of bFGF, we evaluated its efficacy after a more severe contusion injury at T(10) using the NYU impactor. Immediately after SCI, osmotic minipumps were implanted into the lateral ventricle and lumbar thecal sac to deliver bFGF at 3 or 6 microg per day versus control vehicle for 1 week. Animals were behaviorally tested for 6 weeks before histological assessment of tissue sparing through the injured segment and glial reactivity distal to the lesion. Compared to moderate SCI, all rats had more prolonged and sustained functional deficits 6 weeks after severe contusion. Subjects treated with bFGF had pronounced recovery of hindlimb movements from 2 to 6 weeks compared to controls, manifested in significantly higher behavioral scores. Only marginal tissue sparing was seen rostral to the injury in bFGF-treated spinal cords versus controls. Optical density measurements of astrocyte and microglial cell immunoreactivity in bFGF-treated spinal cords showed that after 6 weeks they approximated controls, although astrocyte immunoreactivity remained higher in controls rostrally. In summary, intrathecal infusion of bFGF following severe SCI significantly restores gross hindlimb motor function that is not correlated with significant tissue sparing. In light of previous evidence that pharmacological intervention with bFGF after moderate SCI enhances tissue preservation, the current findings indicate that yet undefined mechanisms contribute to the enhanced functional recovery following bFGF treatment. 0014-4886 Journal Article}, Author = {Rabchevsky, A. G. and Fugaccia, I. and Turner, A. F. and Blades, D. A. and Mattson, M. P. and Scheff, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:58 -0400}, Journal = {Exp Neurol}, Keywords = {Spinal Cord Injuries/*drug therapy/pathology/surgery;Dose-Response Relationship, Drug;Glial Fibrillary Acidic Protein/metabolism;Animals;Rats;Fibroblast Growth Factor 2/*administration &dosage;Lumbosacral Region;Movement/drug effects;Female;Thoracic Vertebrae/surgery;Hindlimb/innervation;Rats, Sprague-Dawley;Injections, Intraventricular;Analysis of Variance;Support, Non-U.S. Gov't;Wounds, Nonpenetrating;Gliosis/metabolism/pathology;Recovery of Function/*drug effects;Injections, Spinal;Laminectomy;04 Adult neurogenesis factors;Membrane Glycoproteins/metabolism;Behavior, Animal/drug effects/physiology;C pdf;Infusion Pumps, Implantable}, Number = {2}, Organization = {Sanders-Brown Center on Aging, University of Kentucky, Lexington, Kentucky 40536-0230, USA.}, Pages = {280-91}, Pubmed = {10915567}, Title = {Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat}, Uuid = {0E66C9F8-92F0-4F61-A7A9-01C7637E24E3}, Volume = {164}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10915567}} @article{Rabchevsky:1997, Abstract = {There is contrasting in vitro and in vivo evidence regarding glial cell involvement in central nervous system (CNS) regeneration. This study has investigated the histological events that follow implantation of either microglia, mixed microglia/astrocytes, or astrocytes into the injured adult rat spinal cord. We have conducted an immunohistochemical characterization of the cellular profiles within and neuritic extension into various grafts consisting of gelfoam (GF) matrices impregnated with cultured microglia and/or astrocytes. After 2-5 weeks, prominent neuritic growth was observed into OX-42-immunoreactive (IR) microglial implants. These grafts were infiltrated by numerous host cellular elements including microvasculature and Schwann cells, and they demonstrated conspicuous laminin IR. Often, the patterns for laminin and OX-42 IR in microglial grafts were overlapping, suggesting partial expression of laminin on transplanted microglial cells. Mixed grafts of microglia and astrocytes demonstrated presence of neurites and laminin-IR elements with similar intensity as microglial grafts, while astroglial implants showed the least amount of neurite ingrowth. Some control implants consisting of cell-free GF showed marginal in-growth of neurites in areas of infiltrating OX-42-IR host cells. Collectively, our findings support a neurite growth-promoting role of activated microglia and suggest that microglia may counteract mechanisms that inhibit CNS regeneration. It remains to be determined whether the observed neurite growth-promoting effects are mediated directly by grafted and/or endogenous microglia, or whether this occurs via the recruitment of host Schwann cells.}, Author = {Rabchevsky, A. G. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Animals;Astrocytes;Cells, Cultured;Rats;Fluorescent Antibody Technique;Microglia;Lipopolysaccharides;Cell Communication;Rats, Sprague-Dawley;Neurites;Not relevant;Gelatin Sponge, Absorbable;11 Glia;Laminin;Nerve Regeneration;Spinal Cord Injuries;Support, Non-U.S. Gov't;Animals, Newborn;Neurons;Host vs Graft Reaction;Support, U.S. Gov't, P.H.S.;Microcirculation;Cell Division;Biological Markers;Data Interpretation, Statistical}, Medline = {97135699}, Month = {1}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Neuroscience, University of Florida College of Medicine, Gainesville 32610, USA.}, Pages = {34-48}, Pii = {10.1002/(SICI)1097-4547(19970101)47:1<34::AID-JNR4>3.0.CO;2-G}, Pubmed = {8981236}, Title = {Grafting of cultured microglial cells into the lesioned spinal cord of adult rats enhances neurite outgrowth}, Uuid = {7020DB5E-3EA4-493B-B255-863BA286B46B}, Volume = {47}, Year = {1997}} @article{Radnikow:2002, Abstract = {Cajal-Retzius (CR) cells are among the earliest generated neurons and are thought to play a role in corticogenesis and early neuronal migration. However, the role of CR cells in an early cortical microcircuit is still rather unclear. We therefore have investigated the morphology and physiology of CR cells by using whole-cell patch-clamp recordings combined with intracellular biocytin filling in acute brain slices of postnatal day 5-11 rats. CR cells are characterized by a long horizontally oriented dendrite; the axonal collaterals form a dense horizontally oriented plexus in layer 1 and to a certain extent in layer 2/3, projecting over >2 mm of cortical surface. The bouton density is relatively high, and synaptic contacts are established preferentially with dendritic spines or shafts of excitatory neurons, presumably terminal tuft dendrites of pyramidal neurons. In turn, CR cells receive dense GABAergic and non-GABAergic input on somata, dendritic shafts, and spine-like appendages. Extracellular stimulation in layer 1 could activate both GABAergic and glutamatergic synaptic inputs. The GABAergic response was blocked by the GABA(A) receptor antagonist bicuculline. The glutamatergic response was mediated solely by NMDA receptors and was highly sensitive to ifenprodil, indicating that it was mediated mainly via NR1/NR2B subunit-containing receptors. NMDA EPSPs were apparent in 1 mm extracellular Mg2+, suggesting that this pure NMDA synapse is not silent functionally. Together, the long-range horizontal projection of the axon, the high density of synaptic boutons, and the functional synaptic input of CR cells suggest that they are an integral part of an early cortical network.}, Author = {Radnikow, Gabriele and Feldmeyer, Dirk and L{\"u}bke, Joachim}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;10 Development;Piperidines;Electric Stimulation;Lysine;Synapses;In Vitro;Rats;Animals;Synaptic Transmission;Neocortex;Patch-Clamp Techniques;Axons;Rats, Wistar;Dendrites;Nerve Net;Support, Non-U.S. Gov't;Neurons;GABA Antagonists;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Medline = {22166801}, Month = {8}, Nlm_Id = {8102140}, Number = {16}, Organization = {Max Planck Institute of Medical Research, Department for Cell Physiology, D-69120 Heidelberg, Germany.}, Pages = {6908-19}, Pii = {22/16/6908}, Pubmed = {12177189}, Title = {Axonal projection, input and output synapses, and synaptic physiology of Cajal-Retzius cells in the developing rat neocortex}, Uuid = {FCC3CB82-E009-476E-9B26-B725434D6222}, Volume = {22}, Year = {2002}, url = {papers/Radnikow_JNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/20026725}} @article{Rafiq:1995, Abstract = {1. Combined hippocampal-parahippocampal slices were employed to study the development of complex epileptiform discharges after Schaeffer collateral stimulation in vitro. With repeated stimulation, slices generated several different types of epileptiform discharges, which were temporally linked to the preceding stimulus, and predictable in their progression. The first epileptiform discharge to be elicited by stimulation was a primary afterdischarge, which began immediately after the stimulation train and progressed with repeated stimulation until it had peaked in amplitude and duration by the third to fifth stimulus train. After development of the primary afterdischarge, a secondary afterdischarge began to appear, with a 2- to 5-min latency after the third to sixth stimulation train, and progressed in amplitude and duration with repeated stimulation, sometimes to durations > 30 min. 2. After development of the secondary afterdischarge, 65-70\%of rostral slices triggered long-duration, spontaneous self-sustained activity. This activity consisted of repeated spontaneous 3- to 5-min duration ictallike discharges with a short interval (< 15 min between events), lasting for hours in many cases. These discharges were similar to activity seen in depth recordings of patients with complex partial status epilepticus. This cyclic spontaneous epileptiform activity was blocked by diazepam (100 nM to 1 microM), and potentiated by the N-methyl-D-aspartate (NMDA) antagonist 2-amino-5-phosphonovaleric acid (APV, 50 microM). Analysis of the temporal progression of epileptiform activity through multiple channel extracellular recordings demonstrated that both the interictal and ictal discharges evident during spontaneous recurrent ictal-like status epilepticus (SE) originated at a site distant from the stimulation locus, and then propagated to area CA1. 3. Intracellular recordings from CA3 neurons during spontaneous recurrent ictallike SE activity revealed the cellular correlates of this activity. Recurrent ictallike discharges were initiated at a cellular level by a large depolarization, accompanied by tonic action-potential firing. As the ictal event progressed, the neuron continued to depolarize, and a period of depolarization block ensued, which was terminated by the gradual repolarization of the neuron, with accompanying phasic burst firing. 4. A second variety of long-duration self-sustained activity was also seen in 5-10\%of slices. This type of continuous sustained activity was initiated by an increase in duration of the secondary afterdischarge to 30-120 min duration with repeated stimulation. These sustained discharges were also increased in amplitude and frequency by APV (50 microM) and reduced or blocked by the benzodiazepines diazepam or clonazepam (1 microM). Sustained epileptiform discharges seen in vitro were similar to one form of seizure discharges seen in patients with SE in their frequency, duration, in their progression through a similar electrographic series of stages, and their sensitivity to benzodiazepines. 5. Intracellular recordings from CA3 neurons during continuous SE-like discharges revealed large bursts within this area during generation of generalized epileptiform activity. These bursts were coincident with extracellularly recorded population burst activity in CA1, and so were a circuit phenomenon. 6. This physiological and pharmacological correspondence between the multiple types of SE-like activity seen in vitro and in patients with SE suggests that these long-duration limbic discharges seen in slices may constitute a valuable model for study of the seizure discharges of SE. Future studies exploiting the advantages of in vitro preparations may aid in understanding physiological and pharmacological factors important in generation and control of this grave neurological condition.}, Author = {Rafiq, A. and Zhang, Y. F. and DeLorenzo, R. J. and Coulter, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Diazepam;Electric Stimulation;Animals;In Vitro;Rats;21 Epilepsy;Entorhinal Cortex;Rats, Sprague-Dawley;Hippocampus;Disease Models, Animal;Time Factors;Male;Status Epilepticus;Research Support, U.S. Gov't, P.H.S.;N-Methylaspartate;21 Neurophysiology;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {96150915}, Month = {11}, Nlm_Id = {0375404}, Number = {5}, Organization = {Department of Neurology, Medical College of Virginia, Richmond 23298-0599, USA.}, Pages = {2028-42}, Pubmed = {8592194}, Title = {Long-duration self-sustained epileptiform activity in the hippocampal-parahippocampal slice: a model of status epilepticus}, Uuid = {328FC7DF-255F-48A7-855A-977E43B52CD4}, Volume = {74}, Year = {1995}} @article{Rafols:1995, Abstract = {The neocortex and the hippocampus were examined for lipid peroxidation products and ultrastructural alterations by fluorescence and electron microscopy, respectively, in rats subjected to 10 min of cardiac arrest or 10 min cardiac arrest and either 90 or 360 min reperfusion. Lipid peroxidation products were observed after 90 min reperfusion in the perikarya and proximal dendrites of neocortical pyramidal neurons and in the hippocampal hilar cells and CA1, region; the fluorescence was most intense at the base of the apical dendrite, the region of the Golgi apparatus. After 90 min of reperfusion, the CA1, showed considerable stretches of rough endoplasmic reticulum devoid of ribosomes and the Golgi cisternae were shorter and widely dilated. The neocortex showed similar endoplasmic reticulum changes, but no significant alterations to the Golgi were noted. In addition there were areas where strings of ribosomes appear to be detaching from the endoplasmic reticulum. After 360 min reperfusion in both the neocortex and the hippocampus, the damage appeared more severe. The Golgi was fragmented into vacuoles, membranous whorls had appeared, and dense aggregates of smooth vesicles were seen coalescing with each other and the vacuoles. These observations suggest that early Golgi involvement is a more important marker of lethal injury than ribosome release from the endoplasmic reticulum. The areas of disturbed Golgi ultrastructure correspond to those areas that show evidence of lipid peroxidation and imply that lipid peroxidation may be causally related to the disturbance in Golgi ultrastructure.}, Author = {Rafols, J. A. and Daya, A. M. and O'Neil, B. J. and Krause, G. S. and Neumar, R. W. and White, B. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Brain Ischemia;Golgi Apparatus;Rats;Microscopy, Electron;Lipid Peroxidation;Hippocampus;Not relevant;Heart Arrest;11 Glia;Cell Death;Support, U.S. Gov't, P.H.S.;Reperfusion;Animals;Support, Non-U.S. Gov't;Rats, Inbred Strains;Fluorescence;Neurons}, Medline = {96057170}, Nlm_Id = {0412041}, Number = {1}, Organization = {Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA.}, Pages = {17-30}, Pubmed = {7572075}, Title = {Global brain ischemia and reperfusion: Golgi apparatus ultrastructure in neurons selectively vulnerable to death}, Uuid = {13B0D8A3-FCA3-49C0-B9C6-38CC9A8AD504}, Volume = {90}, Year = {1995}} @article{Raibon:2002, Abstract = {Intravitreal injection of the microglia inhibitor tuftsin 1-3 leads to an increase in retinal ganglion cell axonal regeneration into peripheral nerve grafts and a decrease in phagocytic cells in the retina. However, the relation of phagocytic cells and particularly microglia towards axonal regeneration remains unclear. Initially, to assess this, tuftsin 1-3's effect on axonal regeneration was reexamined by doing a dose-response study. Optimal doses were found to be 2.5 microg/ml and 250 microg/ml in rats and hamsters respectively. We then studied retinal phagocytic cells in rats. Microglial cells were classified as resting or activated based on their morphology following OX42 immunolabelling. In controls, most microglial cells were in the resting state. Optic nerve cut led to an increase in the total number of microglia and a ten-fold elevation in the proportion of activated cells; changes were more pronounced at the optic nerve stump. Anastomosis of an autologous segment of sciatic nerve to the stump of the freshly cut optic nerve minimized the overall increase in microglia, and combined with 2.5 microg/ml tuftsin 1-3, lead to a marked blunting of activation. Preservation within the retina of a higher proportion of resting over active form of microglia, and not the prevention of microglial proliferation per se, may be a crucial factor in allowing additional retinal ganglion cell axons to regenerate into peripheral nerve grafts.}, Author = {Raibon, E. and Sauv{\'e}, Y. and Carter, D. A. and Gaillard, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Peripheral Nerves;Research Support, Non-U.S. Gov't;Hamsters;Animals;Rats, Inbred BN;Blood Proteins;Rats;Microglia;Female;Antigens, CD;Antigens, Neoplasm;Rats, Sprague-Dawley;Avian Proteins;Cell Count;Antigens, Surface;11 Glia;Axons;Nerve Regeneration;Membrane Glycoproteins;Mesocricetus;Transplants;24 Pubmed search results 2008;Retinal Ganglion Cells}, Medline = {22538728}, Month = {1}, Nlm_Id = {0364620}, Number = {1}, Organization = {UMR 6558 CNRS, Facult{\'e} des Sciences, Poitiers, France.}, Pages = {57-71}, Pii = {5115502}, Pubmed = {12652088}, Title = {Microglial changes accompanying the promotion of retinal ganglion cell axonal regeneration into peripheral nerve grafts}, Uuid = {63220C22-95E1-4509-B0AF-DEA393452581}, Volume = {31}, Year = {2002}} @article{Raivich:2003, Abstract = {Studies using mouse axotomised facial motoneuron model show a strong and highly selective entry of CD3+ lymphocytes into the affected nucleus, with a maximum at Day 14, which coincides with the peak of neuronal cell death, microglial phagocytosis, and increased synthesis of interleukin-1 beta (IL1beta), tumour necrosis factor-alpha (TNFalpha) and interferon-gamma (IFNgamma). We explored the possible involvement of these cytokines during the main phase of lymphocyte recruitment into the axotomised facial motor nucleus 7-21 days after nerve cut using mice homozygously deficient for IL1 receptor type 1 (IL1R1-/-), TNF receptor type 1 (TNFR1-/-), type 2 (TNFR2-/-) and type 1 and 2 (TNFR1&2-/-), IFNgamma receptor type 1 (IFNgammaR1-/-), and the appropriate controls for the genetic background. Transgenic deletion of IL1R1 led to a 54\%decrease and that of TNFR2 to a 44\%reduction in the number of CD3+ T-cells in the axotomised facial motor nucleus, with a similar relative decrease at Day 7, 14, and 21. Deletion of TNFR1 or IFNgammaR1 had no significant effect. Deletion of both TNFR1 and 2 (TNFR1&2-/-) caused a somewhat stronger, 63\%decrease than did TNFR2 deletion alone, but this could be due to an almost complete inhibition of neuronal cell death. No mutations seemed to inhibit aggregation of CD3+ T-cells around glial nodules consisting of Ca-ion binding adaptor protein-1 (IBA1)+ phagocytotic microglia and neuronal debris. Altogether, the current data show the importance of IL1R1 and TNFR2 as the key players during the main phase of lymphocyte recruitment to the damaged part of the central nervous system.}, Author = {Raivich, Gennadij and Bohatschek, Marion and Werner, Alexander and Jones, Leonard L. and Galiano, Matthias and Kloss, Christian U. A. and Zhu, Xing-Zu Z. and Pfeffer, Klaus and Liu, Zhi Qiang}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Receptors, Cytokine;Phagocytosis;Animals;Comparative Study;Lymphocytes;Microglia;Cell Communication;Cell Movement;Mice, Inbred C57BL;Not relevant;11 Glia;Support, Non-U.S. Gov't;Mice, Knockout;Axotomy;Mice;Inflammation;Brain Stem;Facial Nerve;Cytokines}, Medline = {22658411}, Month = {6}, Nlm_Id = {7600111}, Number = {6}, Organization = {Department of Neuromorphology, Max-Planck Institute for Neurobiology, Martinsried, Germany. g.raivich\@ucl.ac.uk}, Pages = {726-33}, Pubmed = {12774313}, Title = {Lymphocyte infiltration in the injured brain: role of proinflammatory cytokines}, Uuid = {99B4BD00-5843-4FFC-9A73-BCD4CAB088CB}, Volume = {72}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10621}} @article{Raivich:2004, Abstract = {Nerve injury triggers numerous changes in the injured neurons and surrounding nonneuronal cells that ultimately result in successful target reinnervation or cell death. c-Jun is a component of the heterodimeric AP-1 transcription factor, and c-Jun is highly expressed in response to neuronal trauma. Here we have investigated the role of c-jun during axonal regeneration using mice lacking c-jun in the central nervous system. After transection of the facial nerve, the absence of c-Jun caused severe defects in several aspects of the axonal response, including perineuronal sprouting, lymphocyte recruitment, and microglial activation. c-Jun-deficient motorneurons were atrophic, resistant to axotomy-induced cell death, and showed reduced target muscle reinnervation. Expression of CD44, galanin, and alpha7beta1 integrin, molecules known to be involved in regeneration, was greatly impaired, suggesting a mechanism for c-Jun-mediated axonal growth. Taken together, our results identify c-Jun as an important regulator of axonal regeneration in the injured central nervous system.}, Author = {Raivich, Gennadij and Bohatschek, Marion and Da Costa, Clive and Iwata, Osuke and Galiano, Matthias and Hristova, Maria and Nateri, Abdolrahman S. and Makwana, Milan and Riera-Sans, Llu{\'\i}s and Wolfer, David P. and Lipp, Hans-Peter P. and Aguzzi, Adriano and Wagner, Erwin F. and Behrens, Axel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Animals;Galanin;Recovery of Function;Neuronal Plasticity;Transcription Factor AP-1;Integrins;Microglia;Lymphocyte Activation;Mice, Transgenic;Antigens, CD44;Atrophy;Not relevant;11 Glia;Proto-Oncogene Proteins c-jun;Nerve Regeneration;Facial Nerve Injuries;Support, Non-U.S. Gov't;Axotomy;Muscle, Skeletal;Down-Regulation;Gliosis;Motor Neurons;Mice;Growth Cones;Cell Death;Facial Nerve}, Month = {7}, Nlm_Id = {8809320}, Number = {1}, Organization = {Perinatal Brain Repair Group, Department of Obstetrics and Gynaecology, University College London, 86-96 Chenies Mews, London WC1E 6HX, United Kingdom.}, Pages = {57-67}, Pii = {S0896627304003575}, Pubmed = {15233917}, Title = {The AP-1 transcription factor c-Jun is required for efficient axonal regeneration}, Uuid = {0921FE53-70BE-42A9-9A35-9C3022739C93}, Volume = {43}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.06.005}} @article{Rakic:1985, Abstract = {Autoradiographic analysis of juvenile and adult monkeys that received single or multiple injection of the specific DNA precursor, [3H]thymidine, demonstrates slight turnover of glial cells, but failed to provide any evidence of either neuronal addition or replacement. Therefore, while the brains of nonmammalian vertebrates and possibly some nonprimate mammals may display variable degrees of postembryonic neurogenesis, all neurons of the primate central nervous system are generated during restricted developmental periods, mostly before birth and not after infancy. It is not surprising that a stable population of neurons in mature primates, including man, may be essential for the retention of memory and learned behavior. Using Smart Source Parsing}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Ann N Y Acad Sci}, Keywords = {Human;Oligodendroglia/cytology;Neurons/*cytology/metabolism;Thymidine/metabolism;Comparative Study;Mitosis;Brain/*cytology/embryology/metabolism;Female;DNA/*biosynthesis;*Aging;Animal;Glial Fibrillary Acidic Protein/analysis;Species Specificity;Male;01 Adult neurogenesis general;Support, Non-U.S. Gov't;Histocytochemistry;Macaca mulatta;Support, U.S. Gov't, P.H.S.;Cell Division;Microscopy, Electron;Autoradiography;A-3;Neuroglia/cytology}, Pages = {193-211}, Title = {DNA synthesis and cell division in the adult primate brain}, Uuid = {6B7E198B-65AD-4AA4-839C-487115867E2D}, Volume = {457}, Year = {1985}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3913364}} @article{Rakic:2006, Abstract = {Within the past 125 years, we have witnessed great strides in understanding development and evolution of the cerebral cortex, arguably the structure that makes us human. Among the distinguishing features of cortical development are discoveries that its constituent neurons are not generated locally and that after assuming their proper areal, radial, and laminar position, they serve the individual throughout the lifespan. Although the basic cellular events and all major developmental phenomena have been discovered by the use of classical methods, advents of new, evermore sophisticated experimental methods that range from neuroimaging to molecular genetics enable elucidation of the molecular and cellular mechanisms underlying evolutionary elaboration of the cortex and opens the possibility for the prevention and treatment of congenital disorders of the highest cognitive functions in humans.}, Author = {Rakic, Pasko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Staining and Labeling;Neurobiology;24 Pubmed search results 2008;Neuronal Plasticity;Silver;Research;Genetic Engineering;Animals;Humans;Cerebral Cortex;review;Organogenesis}, Month = {7}, Nlm_Id = {9110718}, Organization = {Department of Neurobiology and Kavli Institute of Neuroscience, Yale University School of Medicine New Haven, CT 06511, USA. pasko.rakic\@yale.edu}, Pages = {i3-17}, Pii = {16/suppl_1/i3}, Pubmed = {16766705}, Title = {A century of progress in corticoneurogenesis: from silver impregnation to genetic engineering}, Uuid = {99499D8F-75BF-4871-8332-2AEABC42F37A}, Volume = {16 Suppl 1}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhk036}} @article{Rakic:2000, Abstract = {Programmed cell death (PCD) in the form of apoptosis is recognized as one of the central events in the development of the central nervous system. To study the time of onset, extent and distribution of PCD in the human telencephalon, embryos and fetuses from 4.5 to 27 gestational weeks (g.w.) were examined using the TUNEL (TdT-mediated dUTP-biotin nick-end labelling) in situ method. At 4.5 g.w. sparse TUNEL(+) nuclei were observed in the ventricular zone of the neural tube. With the formation of the cortical plate at 7-8 g.w. , TUNEL(+) nuclei were seen in all developmental layers of the cortical anlage, as well as in the subcortical regions such as the ganglionic eminence and the internal capsule. The proliferative zones (the ventricular zone, the subventricular zone and the ganglionic eminence) contained the majority of all apoptotic nuclei observed in each specimen. However, the apoptotic index was highest in the subplate zone and in layer I. Double-labelling experiments suggested that neuronal precursors were the main population of cells undergoing PCD in the first trimester of gestation, whereas glial cells probably start dying around midgestation. The onset of labelling of microglial cells and apoptotic nuclei were synchronous, indicating the involvement of microglia in PCD. In conclusion, two distinct types of PCD were observed during human telencephalic development: embryonic apoptosis, which was synchronous with proliferation and migration of neuronal cells and probably not related to establishment of neuronal circuitry, and fetal apoptosis, which coincided with differentiation and synaptogenesis, and therefore may be related to the development of axonal-target connectivity.}, Author = {Rakic, S. and Zecevic, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Telencephalon;Fetus;Human;Microscopy, Electron;Apoptosis;Stem Cells;Not relevant;11 Glia;Microglia;Support, Non-U.S. Gov't;Neurons;In Situ Nick-End Labeling}, Medline = {20428255}, Month = {8}, Nlm_Id = {8918110}, Number = {8}, Organization = {Department of Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030-3401, USA.}, Pages = {2721-34}, Pii = {ejn153}, Pubmed = {10971615}, Title = {Programmed cell death in the developing human telencephalon}, Uuid = {BB72E8FB-9804-4140-B162-222DA3F078AF}, Volume = {12}, Year = {2000}} @article{Rakic:2003, Abstract = {Since the discovery of radial glial cells in the human fetal forebrain, this specialized cellular population has been identified in most regions of the vertebrate brain during restricted developmental periods. However, their size, longevity, and significance for guiding migrating neurons have increased with the evolutionary expansion of the mammalian neocortex, reaching a peak in the gyrencephalic human forebrain. The phenotypic distinction of radial glial cells from the more specialized neuronal progenitors in the proliferative zones and from the migrating neurons in the intermediate zone of the primate fetal forebrain, based initially on morphological criteria, has been supported by their ultrastructural, molecular, and physiological characteristics. In addition, modern in vivo and in vitro approaches revealed that these specialized embryonic cells can also generate neuronal cell lines, which either immediately, or after several divisions, migrate along radial shaft processes of the mother cells that span the expanding and convoluted cerebral wall. The multiple functions of radial glial cells and their species-specific adaptations indicate a pivotal role in evolution, development, and pathology of the cerebral neocortex. 0894-1491 Historical Article Journal Article Review Review, Academic}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Glia}, Keywords = {History of Medicine, 20th Cent.;Stem Cells/*physiology/ultrastructure;History of Medicine, 19th Cent.;10 Development;Human;Neocortex/*embryology/*growth &development/ultrastructure;Cell Differentiation/physiology;Cell Lineage/physiology;Neurosciences/history;Neuroglia/*physiology/ultrastructure;Animals;F pdf;Neurons/*physiology/ultrastructure;Cell Movement/physiology}, Number = {1}, Organization = {Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, SHM, C-303, New Haven, CT 06510, USA. pasko.rakic\@yale.edu}, Pages = {19-32}, Pubmed = {12761862}, Title = {Elusive radial glial cells: historical and evolutionary perspective}, Uuid = {CF056511-C3C9-4BC0-94BC-637DA9AE6859}, Volume = {43}, Year = {2003}, url = {papers/Rakic_Glia2003.pdf}} @article{Rakic:2003a, Abstract = {Oligodendrocytes, the myelin-producing cells in the central nervous system, represent a large portion of the total number of cells in the human brain. Using cell-specific markers and antibodies to ventral homeodomain transcription factors, NKX2.1 and DLX2, we show here that a subpopulation of early oligodendrocyte progenitor cells (OPCs) in the human telencephalon may originate in the ganglionic eminence (GE). DLX2-labeled OPCs form a well-delineated stream of cells connecting the GE subventricular zone (SVZ) to the cortical intermediate zone through the anterior cortical SVZ. This population of cells is labeled by early OPCs markers, PDGFRalpha, Olig1, and NG2, and not with either neuronal, astrocyte, or late OPCs markers. Intriguingly, numerous CD68(+) microglia/macrophages, nestin(+) neural stem cells, and CD34(+) hematopoietic stem cells (HSCs) are also present in both the GE stream and the cortical SVZ. These cells could be colabeled with DLX2 as well as early OPCs markers. A separate subpopulation of early OPCs, present in the GE and cortical SVZ, did not express either DLX2 or CD68. These findings suggest that different subpopulations of early OPCs, characterized with different sets of transcription factors and cell-specific markers, are present in human forebrain. These subpopulations may have different origins; one may originate in the cortical SVZ, while others may come from the GE and/or outside the CNS as hematopoietic stem cells. 0894-1491 Journal Article}, Author = {Rakic, S. and Zecevic, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Glia}, Keywords = {Neurons/cytology/metabolism;10 Development;Cell Differentiation/*physiology;Fetus;Cell Lineage/*physiology;Human;Immunohistochemistry;Gene Expression Regulation, Developmental/physiology;Support, U.S. Gov't, P.H.S.;Stem Cells/cytology/*metabolism;Telencephalon/cytology/*embryology/metabolism;Support, Non-U.S. Gov't;Cell Movement/*physiology;F pdf;Oligodendroglia/cytology/*metabolism}, Number = {2}, Organization = {Department of Neuroscience, University of Connecticut Medical School, Farmington, Connecticut 06030, USA.}, Pages = {117-27}, Pubmed = {12509802}, Title = {Early oligodendrocyte progenitor cells in the human fetal telencephalon}, Uuid = {A2EF0300-2D9A-41D3-BFD8-FA7CFB09DD4D}, Volume = {41}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12509802}} @article{Rakic:1972, Abstract = {0021-9967 Journal Article}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Comp Neurol}, Keywords = {*Cell Movement;01 Adult neurogenesis general;Gestational Age;Haplorhini;Female;Microscopy, Electron;Cerebral Ventricles/embryology;*Cell Differentiation;Telencephalon/embryology;A,F abstr;Pregnancy;Animals;Cerebral Cortex/cytology/*embryology;Macaca;Neurons}, Number = {1}, Pages = {61-83}, Pubmed = {4624784}, Title = {Mode of cell migration to the superficial layers of fetal monkey neocortex}, Uuid = {7AD4D995-07DB-47D7-9D43-22E76E4D9D23}, Volume = {145}, Year = {1972}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4624784}} @article{Rakic:1981, Abstract = {The time of origin of neurons in the hippocampal region was determined in a series of rhesus monkeys, each of which had been exposed to a pulse of tritiated thymidine (3H-TdR) at a different time during ontogeny and sacrificed between the second and fifth month after birth. No heavily labeled cells were found in the hippocampal region of animals exposed to 3H-TdR before embryonic day 33 (E33). Exposure to 3H-TdR given at E36 labels a few neurons in the deepest layers of the entorhinal area, and 3H-TdR given at E38 labels a small number of neurons in all hippocampal subdivisions. Although the first neurons are generated almost simultaneously throughout the hippocampal region, the proliferation ceases at a different time in each subdivision. The last neurons destined for the entorhinal area and presubiculum are generated between E70 and E75, whereas the last parasubicular neurons are generated between E75 and E80. The production of neurons that form the subiculum ends about two weeks earlier, between E56 and E65. Within the hippocampus, genesis of pyramidal cells ends between E70 and E80 in area CA1, between E56 and E65 in area CA2, between E65 and E80 in area CA1, between E56 and E65 in area CA2, between E65 and E70 in area CA3, and between E75 and E80 in area CA4. In contrast, the genesis of granule cells of the fascia dentata is considerably prolonged. It continues throughout the second half of gestation, declines steadily in the course of the first postnatal month, and tapers off during the next 2 months. There is a distinct inside-to-outside spatiotemporal gradient in the parahippocampal formation and in the stratum pyramidale of both the subiculum and hippocampus. In contrast, the spatiotemporal pattern of granule cell origin in the dentate gyrus is outside-to-inside. Furthermore, granule cells generated between E36 and E80 are distributed in a distinct suprapyramidal-to-infrapyramidal gradient, whereas those generated at later ages are distributed evenly throughout the fascia dentata. Correlation of the present findings with histological data on hippocampal neurogenesis in the human brain demonstrates that the timing and sequence of developmental events as well as spatiotemporal gradients are similar in both primate species.}, Author = {Rakic, P. and Nowakowski, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Aging;Cell Differentiation;Macaca mulatta;Female;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Autoradiography;Cell Count;Pregnancy;Mitosis;Animals;Neurons}, Medline = {81142838}, Month = {2}, Nlm_Id = {0406041}, Number = {1}, Pages = {99-128}, Pubmed = {7204668}, Title = {The time of origin of neurons in the hippocampal region of the rhesus monkey}, Uuid = {AD8AE70C-A3E5-11DA-AB00-000D9346EC2A}, Volume = {196}, Year = {1981}, url = {papers/Rakic_JCompNeurol1981.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901960109}} @article{Rakic:2002, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Human;Cell Differentiation;Neurons/*cytology/metabolism;Animals;Humans;Aging;Cell Cycle/physiology;Thymidine/pharmacokinetics;DNA;Thymidine;Cell Cycle;Aging/physiology;review;Animal;Central Nervous System/cytology;01 Adult neurogenesis general;DNA/biosynthesis;Research Support, U.S. Gov't, P.H.S.;Cell Division/physiology;Neurons;Support, U.S. Gov't, P.H.S.;Cell Division;Central Nervous System;Bromodeoxyuridine/pharmacokinetics;Biological Markers;Cell Differentiation/physiology;Bromodeoxyuridine;A both}, Medline = {21683797}, Month = {2}, Nlm_Id = {8102140}, Number = {3}, Organization = {Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. pasko.rakic\@yale.edu}, Pages = {614-8.}, Pii = {22/3/614}, Pubmed = {11826088}, Title = {Adult neurogenesis in mammals: an identity crisis}, Uuid = {9C09C0D0-D20C-11D9-B244-000D9346EC2A}, Volume = {22}, Year = {2002}, url = {papers/Rakic_JNeurosci2002.pdf}} @article{Rakic:1998, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Nat Neurosci}, Keywords = {01 Adult neurogenesis general;Embryo/cytology;Neurons/*physiology;Stem Cells/physiology/transplantation;Cell Aging/physiology;Human;A-8 both;Animal;Embryo, Nonmammalian/physiology;Brain/cytology/*growth &development}, Number = {8}, Pages = {645-7.}, Title = {Young neurons for old brains?}, Uuid = {F8CCEC2E-6C9A-468A-B768-ACFBA2BCFB03}, Volume = {1}, Year = {1998}, url = {papers/Rakic_NatNeurosci1998.pdf}} @article{Rakic:2005, Author = {Rakic, Pasko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Embryonic Development;10 Development;Stem Cells;Signal Transduction;Organ Size;Cell Death;Mitosis;Ephrins;Animals;Humans;Cerebral Cortex;24 Pubmed search results 2008;news}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Pages = {981-2}, Pii = {nn0805-981}, Pubmed = {16047024}, Title = {Less is more: progenitor death and cortical size}, Uuid = {1B73313A-14FC-4B26-BB23-8DFF527D2DEC}, Volume = {8}, Year = {2005}, url = {papers/Rakic_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0805-981}} @article{Rakic:2002a, Abstract = {Reports of continuous genesis and turnover of neurons in the adult primate association neocortex--the site of the highest cognitive functions--have generated great excitement. Here, I review the available evidence, and question the scientific basis of this claim.}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:30 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {DNA/metabolism;Neuroglia/cytology/physiology;Cell Cycle/physiology;Antimetabolites/metabolism;Bromodeoxyuridine/metabolism;Models, Neurological;Neurons/cytology/*physiology;Biological Markers;A both;Nucleotides/metabolism;Animal;Neocortex/*cytology/*physiology;Macaca}, Number = {1}, Organization = {Pasko Rakic is at the Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA. pasko.rakic\@yale.edu}, Pages = {65-71.}, Title = {Neurogenesis in adult primate neocortex: an evaluation of the evidence}, Uuid = {8E1DA188-CDF0-11D9-B244-000D9346EC2A}, Volume = {3}, Year = {2002}, url = {papers/Rakic_NatRevNeurosci2002.pdf}} @article{Rakic:2004, Abstract = {1476-4687 Comment News}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {Nature}, Keywords = {*Cell Movement;01 Adult neurogenesis general;Ki-67 Antigen/analysis;Species Specificity;Rodentia/physiology;Olfactory Bulb/cytology;Human;Multipotent Stem Cells/*cytology;Neurons/*cytology;Nerve Net/cytology;Astrocytes/*cytology;Animals;Brain/*cytology;Nerve Regeneration/physiology;A pdf}, Number = {6976}, Pages = {685-6}, Title = {Neuroscience: immigration denied}, Uuid = {28BEF740-D919-48FA-B12B-281354B46F12}, Volume = {427}, Year = {2004}, url = {papers/Rakic_Nature2004.pdf}} @article{Rakic:1995, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:56 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Nucleic Acid Probes;*Cell Movement;*Models, Neurological;Cell Differentiation;Neurons/*physiology;Cerebral Cortex/anatomy &histology/cytology/*embryology;Clone Cells;H both;Animal;Mice, Transgenic;12 Interneuron development;Mice;Macaca}, Number = {25}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.}, Pages = {11323-7.}, Title = {Radial versus tangential migration of neuronal clones in the developing cerebral cortex}, Uuid = {5B6DDEF1-C0DB-4376-B65E-891F47EA6256}, Volume = {92}, Year = {1995}, url = {papers/Rakic_ProcNatlAcadSciUSA1995.pdf}} @article{Rakic:1974, Abstract = {0036-8075 Journal Article}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Science}, Keywords = {Visual Cortex/cytology/*embryology;Cell Differentiation;Gestational Age;Haplorhini;Female;Autoradiography;Thymidine/metabolism;Neurons/*cytology;Brain Mapping;Pregnancy;N;Animals;Macaca;Cell Movement;19 Neocortical evolution;Tritium}, Number = {123}, Pages = {425-7}, Pubmed = {4203022}, Title = {Neurons in rhesus monkey visual cortex: systematic relation between time of origin and eventual disposition}, Uuid = {E8FFAD07-1986-4D25-AAF2-191529831FC1}, Volume = {183}, Year = {1974}, url = {papers/Rakic_Science1974.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4203022}} @article{Rakic:1985a, Abstract = {Systematic analysis of autoradiograms prepared from postpubertal rhesus monkeys given single and multiple injections of tritium-labeled thymidine and killed 3 days to 6 years later displayed a slow turnover of glial cells but failed to reveal any radiolabeled neurons. Therefore, unlike neurons of some nonprimate species, all neurons of the rhesus monkey brain are generated during prenatal and early postnatal life. A stable population of neurons in primates, including humans, may be important for the continuity of learning and memory over a lifetime.}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Science}, Keywords = {DNA/biosynthesis;Amphibia/growth &development;Human;Female;Autoradiography;Birds/growth &development;Animal;Pregnancy;Support, U.S. Gov't, P.H.S.;Neurons/physiology;Macaca mulatta/growth &development;A-4;Fishes/growth &development;Brain/cytology/*growth &development}, Number = {4690}, Pages = {1054-6.}, Title = {Limits of neurogenesis in primates}, Uuid = {BAA15134-C26D-11DA-969D-000D9346EC2A}, Volume = {227}, Year = {1985}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=3975601}} @article{Rakic:1988, Abstract = {How the immense population of neurons that constitute the human cerebral neocortex is generated from progenitors lining the cerebral ventricle and then distributed to appropriate layers of distinctive cytoarchitectonic areas can be explained by the radial unit hypothesis. According to this hypothesis, the ependymal layer of the embryonic cerebral ventricle consists of proliferative units that provide a proto-map of prospective cytoarchitectonic areas. The output of the proliferative units is translated via glial guides to the expanding cortex in the form of ontogenetic columns, whose final number for each area can be modified through interaction with afferent input. Data obtained through various advanced neurobiological techniques, including electron microscopy, immunocytochemistry, [3H]thymidine and receptor autoradiography, retrovirus gene transfer, neural transplants, and surgical or genetic manipulation of cortical development, furnish new details about the kinetics of cell proliferation, their lineage relationships, and phenotypic expression that favor this hypothesis. The radial unit model provides a framework for understanding cerebral evolution, epigenetic regulation of the parcellation of cytoarchitectonic areas, and insight into the pathogenesis of certain cortical disorders in humans. 0036-8075 Journal Article Review Review, Tutorial}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-22 12:19:13 -0400}, Journal = {Science}, Keywords = {Neurons/physiology;Human;Neuronal Plasticity;Cell Division;Cerebral Cortex/*anatomy &histology/growth &development/physiology;N;Visual Cortex/physiology;Animals;Cell Movement;Support, U.S. Gov't, P.H.S.;Afferent Pathways/physiology;19 Neocortical evolution; visual system; visual cortex; Occipital Lobe; Binocular; monocular; Competitive Behavior; 21 Activity-development; structural remodeling; Structure-Activity Relationship; Afferent Pathways; retina; monkey; Macaca fascicularis}, Number = {4862}, Organization = {Yale University School of Medicine, New Haven, CT 06510.}, Pages = {170-6}, Pubmed = {3291116}, Title = {Specification of cerebral cortical areas}, Uuid = {194D5146-0933-44C5-8C07-B888368EE7BC}, Volume = {241}, Year = {1988}, url = {papers/Rakic_Science1988.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3291116}} @article{Rakic:2006a, Author = {Rakic, Pasko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Adult;Cell Proliferation;Spectrum Analysis, Mass;DNA;Neocortex;Evolution;Carbon Radioisotopes;Humans;Animals;Neurons;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0404511}, Number = {5789}, Organization = {Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA. pasko.rakic\@yale.edu}, Pages = {928-9}, Pii = {313/5789/928}, Pubmed = {16917050}, Title = {Neuroscience. No more cortical neurons for you}, Uuid = {54588B9D-894A-4263-AD6E-697F4BB34410}, Volume = {313}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1131713}} @article{Rakic:1995a, Abstract = {The more than 1000-fold increase in the cortical surface without a comparable increase in its thickness during mammalian evolution is explained in the context of the radial-unit hypothesis of cortical development. According to the proposed model, cortical expansion is the result of changes in proliferation kinetics that increase the number of radial columnar units without changing the number of neurons within each unit significantly. Thus, mutation of a regulatory gene(s) that controls the timing and ratio of symmetric and asymmetric modes of cell divisions in the proliferative zone, coupled with radial constraints in the distribution of migrating neurons, could create an expanded cortical plate with enhanced capacity for establishing new patterns of connectivity that are validated through natural selection. 0166-2236 Journal Article Review Review, Tutorial}, Author = {Rakic, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Trends Neurosci}, Keywords = {Neurons/*physiology;Cell Division/physiology;Cerebral Cortex/anatomy &histology/*cytology/physiology;Human;Support, U.S. Gov't, P.H.S.;N;*Evolution;Animals;Support, Non-U.S. Gov't;19 Neocortical evolution}, Number = {9}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.}, Pages = {383-8}, Pubmed = {7482803}, Title = {A small step for the cell, a giant leap for mankind: a hypothesis of neocortical expansion during evolution}, Uuid = {16D2DEF5-092B-4A77-85D4-5038B9B5BE73}, Volume = {18}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7482803}} @article{Ramdya:2006, Abstract = {Reverse correlation techniques provide a quantitative means of computing neuronal input/output relationships. Until now these methods have been limited to electrically recorded responses since unprocessed optical signals generally lack necessary temporal characteristics. We sought to overcome this barrier since combining reverse correlation with calcium imaging would afford a powerful alternative to current methods of measuring response properties of neurons non-invasively in vivo. We labeled zebrafish optic tecta with a calcium indicator and measured responses to a whole-field random flicker light stimulus. Although calcium signals exhibited slow decay kinetics, we could use computational modeling to show that the positive differential of these traces extracts high frequency information. Experimentally, we found that calcium signals processed in this way were synchronous with simultaneously measured synaptic responses and could be used with reverse correlation to determine temporal filters of neurons in the zebrafish optic tectum. These findings demonstrate that calcium responses to physiological stimulation can be processed to obtain rapid signal information and consequently to determine linear filter properties in vivo.}, Author = {Ramdya, Pavan and Reiter, Bettina and Engert, Florian}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Photic Stimulation;Zebrafish;research support, non-u.s. gov't;21 Neurophysiology;Models, Neurological;Evoked Potentials, Visual;21 Calcium imaging;Diagnostic Imaging;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;Calcium Signaling;Animals;Patch-Clamp Techniques;Superior Colliculi;Neurons;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {7905558}, Number = {2}, Organization = {Program in Neuroscience, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA. ramdya\@fas.harvard.edu}, Pages = {230-7}, Pii = {S0165-0270(06)00224-X}, Pubmed = {16765450}, Title = {Reverse correlation of rapid calcium signals in the zebrafish optic tectum in vivo}, Uuid = {E1B71881-580F-4C4E-8492-E487E70607AE}, Volume = {157}, Year = {2006}, url = {papers/Ramdya_JNeurosciMethods2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2006.04.021}} @article{Ramdya:2008, Abstract = {Sensory circuits frequently integrate converging inputs while maintaining precise functional relationships between them. For example, in mammals with stereopsis, neurons at the first stages of binocular visual processing show a close alignment of receptive-field properties for each eye. Still, basic questions about the global wiring mechanisms that enable this functional alignment remain unanswered, including whether the addition of a second retinal input to an otherwise monocular neural circuit is sufficient for the emergence of these binocular properties. We addressed this question by inducing a de novo binocular retinal projection to the larval zebrafish optic tectum and examining recipient neuronal populations using in vivo two-photon calcium imaging. Notably, neurons in rewired tecta were predominantly binocular and showed matching direction selectivity for each eye. We found that a model based on local inhibitory circuitry that computes direction selectivity using the topographic structure of both retinal inputs can account for the emergence of this binocular feature.}, Author = {Ramdya, and Engert,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Zebrafish;optical physiology;optical imaging;calcium imaging;visual system;21 Activity-development;development;visual experience;Sensory Deprivation;structural remodeling;synapse formation;Circuit structure-function;optic tectum}, Month = {8}, Nlm_Id = {9809671}, Organization = {[1] Program in Neuroscience, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA. [2] Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, Massachusetts 02138, USA.}, Pii = {nn.2166}, Pubmed = {18690231}, Title = {Emergence of binocular functional properties in a monocular neural circuit}, Uuid = {19B8FFAD-8EAF-424F-B777-8D66F181F720}, Year = {2008}, url = {papers/Ramdya_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2166}} @article{Rami:1987, Abstract = {An immunocytochemical study of cholecalcin (28-kDa calcium-binding protein, CaBP, calbindin) was carried out during the development of the rat hippocampus. In normal animals, the protein appeared from Postnatal Day 3 in the granule cells of the dentate gyrus and from Day 5 in the CA1-CA2 pyramidal cells of Ammon's horn. The cells of both regions thus showed positive cholecalcin labeling about 1 week after their formation. The sequence of labeling of the granule cells was a reflection of the major sequences of neurogenesis. Cholecalcin could not be detected in hippocampal cells until dendritic arborization and axon growth had occurred. There was a good correlation between the appearance of cholecalcin and the onset of synaptogenesis. In animals with an experimentally altered thyroid state, in which hippocampal development is retarded or accelerated due to abnormal cell maturation, cholecalcin appearance was similarly retarded or accelerated. Cholecalcin seems to be synthesized at the same time as the hippocampal cells become functional.}, Author = {Rami, A. and Br{\'e}hier, A. and Thomasset, M. and Rabi{\'e}, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {10 Development;10 Hippocampus;Tissue Distribution;Animals;Synapses;Aging;Rats;Comparative Study;Immunoenzyme Techniques;Thyroxine;Hippocampus;Rats, Inbred Strains;Calcium-Binding Protein, Vitamin D-Dependent;Animals, Newborn;Hypothyroidism;Histocytochemistry;Hyperthyroidism;Research Support, Non-U.S. Gov't}, Medline = {88030416}, Month = {11}, Nlm_Id = {0372762}, Number = {1}, Organization = {CNRS UA 1197, Universit{\'e} des Sciences et Techniques du Languedoc, Montpellier, France.}, Pages = {228-38}, Pubmed = {3311850}, Title = {Cholecalcin (28-kDa calcium-binding protein) in the rat hippocampus: development in normal animals and in altered thyroid states. An immunocytochemical study}, Uuid = {A6B90A8B-B0C5-4439-BE5E-9CA5A840F3B4}, Volume = {124}, Year = {1987}} @article{Ramirez-Amaya:2006, Abstract = {Although it is established that new granule cells can be born and can survive in the adult mammalian hippocampus, there remains some question concerning the functional integration of these neurons into behaviorally relevant neural networks. By using high-resolution confocal microscopy, we have applied a new strategy to address the question of functional integration of newborn neurons into networks that mediate spatial information processing and memory formation. Exploration-induced expression of the immediate-early gene Arc in hippocampal cells has been linked to cellular activity observed in electrophysiological recordings under the same behavioral conditions. We investigated whether mature (5-month-old), newborn granule cells express Arc in response to a discrete spatial experience by detecting the expression of Arc in combination with NeuN (neuron-specific nuclear protein)-positive and bromodeoxyuridine-positive cells. We found that mature new granule cells do indeed express Arc in response to an exploration experience, supporting the idea that these cells are well integrated into hippocampal circuits. The proportion of mature newborn neurons that expressed Arc in response to exploration, however, was significantly higher (approximately 2.8\%) than the proportion of cells that expressed Arc in the already existing population of granule cells (approximately 1.6\%; p < 0.01). This finding extends previous data suggesting that the cellular physiology of newborn granule neurons differs from that of the existing population by indicating that these properties are retained in mature adult-generated neurons. Thus, these data have interesting implications for network models of spatial information processing and the role of hippocampal circuits in memory, indicating that mature new neurons are selectively recruited into hippocampal cell assemblies in higher proportions than older cells.}, Author = {Ramirez-Amaya, Victor and Marrone, Diano F. and Gage, Fred H. and Worley, Paul F. and Barnes, Carol A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {in vitro;Animals;Gene Expression Regulation;Rats;Neuronal Plasticity;Microscopy, Confocal;comparative study;Exploratory Behavior;Phosphopyruvate Hydratase;Cell Count;Hippocampus;research support, non-u.s. gov't;Behavior, Animal;01 Adult neurogenesis general;Rats, Inbred F344;Analysis of Variance;Nerve Net;Neurons;research support, n.i.h., extramural;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine;Nerve Tissue Proteins;Cytoskeletal Proteins}, Month = {11}, Nlm_Id = {8102140}, Number = {47}, Organization = {Arizona Research Laboratories Division of Neural Systems, Memory, and Aging, University of Arizona, Tucson, Arizona 85724, USA.}, Pages = {12237-41}, Pii = {26/47/12237}, Pubmed = {17122048}, Title = {Integration of new neurons into functional neural networks}, Uuid = {E64B3B4F-8A51-4031-8EC6-5693942DEA32}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2195-06.2006}} @article{Ramirez-Castillejo:2002, Abstract = {The lizard medial cortex, a region homologous to the mammalian dentate gyrus, shows postnatal neurogenesis and the surprising ability to replace its neurons after being lesioned specifically with the neurotoxin 3-acetylpyridine. As the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) is expressed during neuronal migration and differentiation, we have studied its distribution in adult lizards and also during the lesion-regeneration process. In the medial cortex of control animals, many labeled fusiform somata, presumably corresponding to migratory neuroblasts, appeared in the inner plexiform layer. There were also scattered immunoreactive granule neurons in the cell layer. Double immunocytochemistry with 5'-bromodeoxyuridine revealed that some of the PSA-NCAM-expressing cells in the inner plexiform and cell layers were generated recently. PSA-NCAM immunoreactivity was also present in the dorsomedial, dorsal, and lateral cortices, as well as in the dorsal ventricular ridge, the nucleus accumbens, and the nucleus sphericus. Twelve hours after the injection of 3-acetylpyridine, some medial cortex granule neurons appeared degenerated, although some of them still expressed PSA-NCAM. One to 2 days after the injection, most granule neurons appeared degenerated and no PSA-NCAM immunoreactivity was detected in the medial cortex cell layer. Four to 7 days after treatment, abundant labeled fusiform cells populated the inner plexiform layer and some immunoreactive somata were seen in the cell layer. Fifteen to 30 days after the neurotoxin injection, the number of PSA-NCAM expressing granule neurons augmented considerably and the level was still above control levels in lizards that survived 42 days. Our results show for the first time the expression of PSA-NCAM in a reptile brain, where it appears to participate in the migration and differentiation of granule neurons during adult neurogenesis and regeneration.}, Author = {Ramirez-Castillejo, Carmen and Nacher, Juan and Molowny, Asuncion and Ponsoda, Xavier and Lopez-Garcia, Carlos}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Neurons;Animals;Nerve Fibers;Research Support, Non-U.S. Gov't;Nerve Regeneration;Immunohistochemistry;Neural Cell Adhesion Molecule L1;Hippocampus;Antibodies, Monoclonal;Biological Markers;Cell Division;Lizards;Age Factors;Bromodeoxyuridine;24 Pubmed search results 2008;Sialic Acids;Cerebral Cortex}, Medline = {22260352}, Month = {11}, Nlm_Id = {0406041}, Number = {2}, Organization = {Neurobiologia, Biologia Celular, Facultad de Ciencias Biologicas, Universidad de Valencia, 46100 Burjassot, Spain.}, Pages = {145-56}, Pubmed = {12373780}, Title = {PSA-NCAM immunocytochemistry in the cerebral cortex and other telencephalic areas of the lizard Podarcis hispanica: differential expression during medial cortex neuronal regeneration}, Uuid = {DBCD6088-B4CB-4505-B590-AE0EB0D93E9E}, Volume = {453}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10390}} @article{Ramirez-Castillejo:2006, Abstract = {Adult stem cells are characterized by self-renewal and multilineage differentiation, and these properties seem to be regulated by signals from adjacent differentiated cell types and by extracellular matrix molecules, which collectively define the stem cell "niche." Self-renewal is essential for the lifelong persistence of stem cells, but its regulation is poorly understood. In the mammalian brain, neurogenesis persists in two germinal areas, the subventricular zone (SVZ) and the hippocampus, where continuous postnatal neuronal production seems to be supported by neural stem cells (NSCs). Here we show that pigment epithelium-derived factor (PEDF) is secreted by components of the murine SVZ and promotes self-renewal of adult NSCs in vitro. In addition, intraventricular PEDF infusion activated slowly dividing stem cells, whereas a blockade of endogenous PEDF decreased their cycling. These data demonstrate that PEDF is a niche-derived regulator of adult NSCs and provide evidence for a role for PEDF protein in NSC maintenance.}, Author = {Ram{\'\i}rez-Castillejo, Carmen and S{\'a}nchez-S{\'a}nchez, Francisco and Andreu-Agull{\'o}, Celia and Ferr{\'o}n, Sacri R. and Aroca-Aguilar, J. Daniel and S{\'a}nchez, Pilar and Mira, Helena and Escribano, Julio and Fari\~{n}as, Isabel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Serpins;Research Support, Non-U.S. Gov't;Cell Differentiation;Signal Transduction;Animals;Cells, Cultured;Humans;Neuronal Plasticity;Cell Cycle;Cercopithecus aethiops;Telencephalon;Hippocampus;Eye Proteins;COS Cells;Cell Proliferation;Nerve Growth Factors;Injections, Intraventricular;Neurons;Ependyma;Mice;Cell Division;24 Pubmed search results 2008;Stem Cells;Lateral Ventricles;Endothelium, Vascular}, Month = {3}, Nlm_Id = {9809671}, Number = {3}, Organization = {Departamento de Biolog{\'\i}a Celular, Universidad de Valencia, Burjassot 46100, Spain.}, Pages = {331-9}, Pii = {nn1657}, Pubmed = {16491078}, Title = {Pigment epithelium-derived factor is a niche signal for neural stem cell renewal}, Uuid = {F859D6C5-03BC-41FA-A4BB-8DF9EB7EC11C}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1657}} @article{Ramoa:1994, Abstract = {The maturation of retinogeniculate excitatory transmission and intrathalamic inhibition was studied in slices of the dorsal LGN obtained from ferrets during the first 2 postnatal months. Response to optic tract stimulation at neonatal ages consisted of slow EPSPs lasting several hundred milliseconds. Application of the NMDA receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-APV) during the first 2 postnatal weeks resulted in EPSPs that were reduced in peak amplitude and dramatically curtailed in duration, indicating that NMDA receptors participate strongly in retinogeniculate transmission at the immature synapse. Gradually, EPSPs became shorter in duration such that after the second postnatal week, the retinogeniculate EPSPs were only a few milliseconds in duration. At this late stage of development responses were remarkably less affected by application of D-APV. These changes in contribution of NMDA receptors to retinogeniculate transmission were found to be due to the development of strong IPSPs, the result of gradual maturation of activation of GABAergic inhibition. Indeed, application of bicuculline methiodide to block GABAA receptor-mediated IPSPs strongly enhanced the NMDA component of the EPSPs in more mature cells. The voltage dependence and kinetics of NMDA-induced excitatory postsynaptic currents (NMDA EPSCs) were characterized by voltage-clamp recordings after blocking AMPA/kainate receptors with 6-cyano-7-nitroquinoxaline-2,3-dione and GABAA receptors wit' bicuculline methiodide. The voltage dependence of the NMDA EPSCs remained unaltered with age. During the first postnatal month the kinetic properties of the NMDA EPSCs also remained unaltered, but a reduction in EPSC duration was observed within the following weeks, well after the critical period of anatomical reorganization.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Ramoa, A. S. and McCormick, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Retina;Electric Stimulation;Animals;Synapses;Ferrets;Aging;Evoked Potentials;Afferent Pathways;Synaptic Transmission;Visual Pathways;2-Amino-5-phosphonovalerate;Kinetics;Time Factors;Bicuculline;Quinoxalines;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Neurons;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Geniculate Bodies;in vitro}, Month = {4}, Nlm_Id = {8102140}, Number = {4}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510.}, Pages = {2098-105}, Pubmed = {7908957}, Title = {Enhanced activation of NMDA receptor responses at the immature retinogeniculate synapse}, Uuid = {DABA952B-BE03-4229-8441-3637511EF240}, Volume = {14}, Year = {1994}} @article{Ramoa:1994a, Abstract = {Changes in electrophysiological properties of neurons in the ferret dorsal LGN (LGNd) were studied during early postnatal life, a critical developmental period when changes occur in morphology, connectivity, and response properties of LGNd neurons. Using the patch-clamp technique to obtain whole-cell recordings from cells maintained as in vitro slices of thalamus, several distinctive properties were observed in the immature LGNd. Relatively low resting membrane potentials were present that became more negative during the first 2 postnatal weeks. In addition, immature neurons exhibited high input resistances that decreased during early postnatal development. At all ages postnatally, neurons were capable of generating a train of Na(+)-dependent action potentials in response to intracellular injection of a depolarizing current pulse. Moreover, immature neurons resembled older cells in that little spike frequency adaptation was present during a train of action potentials. Action potential activity in immature neurons was nevertheless distinctive in several respects: (1) during the first 2-3 postnatal weeks action potentials became shorter in duration and larger in amplitude; (2) during the same period, thresholds for generation of action potentials changed in conjunction with the changes in resting membrane potential, becoming more negative; and (3) plots of frequency versus injected current revealed that thresholds for generation of trains of action potentials were reached with intracellular injection of lower current levels at earlier ages. These findings raise the possibility that relatively weak ionic currents generated at immature synapses have unexpectedly strong effects on the young LGNd neuron.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Ramoa, A. S. and McCormick, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Retina;Electrophysiology;Animals;Ferrets;Cesium;Aging;Visual Pathways;Kinetics;Calcium;Tetrodotoxin;Time Factors;Potassium;Thalamus;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Neurons;Membrane Potentials;24 Pubmed search results 2008;Geniculate Bodies;in vitro}, Month = {4}, Nlm_Id = {8102140}, Number = {4}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510.}, Pages = {2089-97}, Pubmed = {8158259}, Title = {Developmental changes in electrophysiological properties of LGNd neurons during reorganization of retinogeniculate connections}, Uuid = {723F6C87-79AB-4AFE-B9B3-FED09AF1DBAB}, Volume = {14}, Year = {1994}, url = {papers/Ramoa_JNeurosci1994.pdf}} @article{Ramos:2005, Abstract = {Subcortical band heterotopia (SBH) or double cortex is associated with significant impairments in neocortical function including mental retardation and epilepsy. Mutant alleles of DCX in humans typically cause SBH in females and lissencephaly in males, whereas Dcx null mutations in mice neither disrupt neocortical neuronal migration nor cause SBH formation. In utero RNA interference (RNAi) of Dcx in rats, in contrast, creates an animal model of SBH. Possible explanations for the discrepancies in results following loss of Dcx function include species differences and/or differences between RNAi knockdown and genetic deletion. We have carried out a series of in utero RNAi experiments to investigate possible species differences between rat and mouse to determine the molecular specificity of RNAi against Dcx and to identify the cellular constituents of SBH in the rat model. In utero RNAi in the rat consistently leads to both the formation of SBH and laminar displacement of transfected cells in normotopic cortex, whereas the same treatment in mouse fails to induce SBH but does create laminar displacement. Induction of SBH and impaired radial migration following RNAi against Dcx is rescued by overexpression of Dcx. Thus, both disruptions induced by RNAi are specific to interference of Dcx. SBHs contain transfected pyramidal cells as well as nontransfected cell types, including neocortical interneurons and glia. Together these results indicate that there is a species difference between rat and mouse with respect to RNAi-induced SBH formation and that SBH formation involves the recruitment of several unaltered cell types.}, Author = {Ramos, and Bai, and Loturco,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {10 Development;Mice, Knockout;Species Specificity;Rats;Neuropeptides;Neocortex;RNA Interference;research support, n.i.h., extramural;comparative study;Nerve Net;Animals;Microtubule-Associated Proteins;24 Pubmed search results 2008;Mice}, Month = {11}, Nlm_Id = {9110718}, Number = {9}, Organization = {Department of Psychology, University of Connecticut, Storrs, CT 06269, USA.}, Pages = {1323-31}, Pii = {bhj074}, Pubmed = {16292002}, Title = {Heterotopia Formation in Rat but Not Mouse Neocortex after RNA Interference Knockdown of DCX}, Uuid = {26E81BA2-334E-4D5A-A195-A9AAA4A07420}, Volume = {16}, Year = {2005}, url = {papers/Ramos_CerebCortex2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhj074}} @article{Rao:1999, Abstract = {Studies on the cellular mechanisms of working memory demonstrated that neurons in dorsolateral prefrontal cortex (dPFC) exhibit directionally tuned activity during an oculomotor delayed response. To determine the particular contributions of pyramidal cells and interneurons to spatial tuning in dPFC, we examined both individually and in pairs the tuning properties of regular-spiking (RS) and fast-spiking (FS) units that represent putative pyramidal cells and interneurons, respectively. Our main finding is that FS units possess spatially tuned sensory, motor, and delay activity (i. e., "memory fields") similar to those found in RS units. Furthermore, when recorded simultaneously at the same site, the majority of neighboring neurons, whether FS or RS, displayed isodirectional tuning, i.e., they shared very similar tuning angles for the sensory and delay phases of the task. As the trial entered the response phase of the task, many FS units shifted their direction of tuning and became cross-directional to adjacent RS units by the end of the trial. These results establish that a large part of inhibition in prefrontal cortex is spatially oriented rather than being untuned and simply regulating the threshold response of pyramidal cell output. Moreover, the isodirectional tuning between adjacent neurons supports a functional microcolumnar organization in dPFC for spatial memory fields similar to that found in other areas of cortex for sensory receptive fields. 0022-3077 Journal Article}, Author = {Rao, S. G. and Williams, G. V. and Goldman-Rakic, P. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurophysiol}, Keywords = {18 Classic Neuroanatomy Physiology;Neural Inhibition/physiology;Prefrontal Cortex/*cytology/physiology;Conditioning (Psychology)/physiology;Action Potentials/physiology;Macaca mulatta;Neurons, Afferent/*physiology;Oculomotor Nerve/cytology/physiology;Memory, Short-Term/*physiology;Visual Fields/physiology;M;Support, U.S. Gov't, P.H.S.;Electrophysiology;Interneurons/*physiology;Animals;Pyramidal Cells/*physiology}, Number = {4}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Pages = {1903-16}, Pubmed = {10200225}, Title = {Isodirectional tuning of adjacent interneurons and pyramidal cells during working memory: evidence for microcolumnar organization in PFC}, Uuid = {A5EA27F9-14FD-4A65-A7CF-F025B865E9DC}, Volume = {81}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10200225}} @article{Raponi:2007, Abstract = {During the postnatal development, astrocytic cells in the neocortex progressively lose their neural stem cell (NSC) potential, whereas this peculiar attribute is preserved in the adult subventricular zone (SVZ). To understand this fundamental difference, many reports suggest that adult subventricular GFAP-expressing cells might be maintained in immature developmental stage. Here, we show that S100B, a marker of glial cells, is absent from GFAP-expressing cells of the SVZ and that its onset of expression characterizes a terminal maturation stage of cortical astrocytic cells. Nevertheless, when cultured in vitro, SVZ astrocytic cells developed as S100B expressing cells, as do cortical astrocytic cells, suggesting that SVZ microenvironment represses S100B expression. Using transgenic s100b-EGFP cells, we then demonstrated that S100B expression coincides with the loss of neurosphere forming abilities of GFAP expressing cells. By doing grafting experiments with cells derived from beta-actin-GFP mice, we next found that S100B expression in astrocytic cells is repressed in the SVZ, but not in the striatal parenchyma. Furthermore, we showed that treatment with epidermal growth factor represses S100B expression in GFAP-expressing cells in vitro as well as in vivo. Altogether, our results indicate that the S100B expression defines a late developmental stage after which GFAP-expressing cells lose their NSC potential and suggest that S100B expression is repressed by adult SVZ microenvironment.}, Author = {Raponi, Eric and Agenes, Fabien and Delphin, Christian and Assard, Nicole and Baudier, Jacques and Legraverend, Catherine and Deloulme, Jean-Christophe C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8806785}, Number = {2}, Organization = {INSERM, EMI 01-04, Grenoble, France.}, Pages = {165-77}, Pubmed = {17078026}, Title = {S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage}, Uuid = {B9EC7A24-A1C9-4A12-B33F-B6120B28B2DA}, Volume = {55}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20445}} @article{Rappert:2004, Abstract = {Microglia are the resident macrophage population of the CNS and are considered its major immunocompetent elements. They are activated by any type of brain pathology and can migrate to the lesion site. The chemokine CXCL10 is expressed in neurons in response to brain injury and is a signaling candidate for activating microglia and directing them to the lesion site. We recently identified CXCR3, the corresponding receptor for CXCL10, in microglia and demonstrated that this receptor system controls microglial migration. We have now tested the impact of CXCR3 signaling on cellular responses after entorhinal cortex lesion. In wild-type mice, microglia migrate within the first 3 d after lesion into the zone of axonal degeneration, where 8 d after lesion denervated dendrites of interneurons are subsequently lost. In contrast, the recruitment of microglia was impaired in CXCR3 knock-out mice, and, strikingly, denervated distal dendrites were maintained in zones of axonal degeneration. No differences between wild-type and knock-out mice were observed after facial nerve axotomy, as a lesion model for assessing microglial proliferation. This shows that CXCR3 signaling is crucial in microglia recruitment but not proliferation, and this recruitment is an essential element for neuronal reorganization.}, Author = {Rappert, Angelika and Bechmann, Ingo and Pivneva, Tatyana and Mahlo, Jacqueline and Biber, Knut and Nolte, Christiane and Kovac, Adam D. and Gerard, Craig and Boddeke, Hendrikus W. G. M. and Nitsch, Robert and Kettenmann, Helmut}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia}, Month = {9}, Nlm_Id = {8102140}, Number = {39}, Organization = {Department of Cellular Neuroscience, Max Delbr{\"u}ck Center for Molecular Medicine, 13092 Berlin, Germany.}, Pages = {8500-9}, Pii = {24/39/8500}, Pubmed = {15456824}, Title = {CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion}, Uuid = {3463ECDC-EE15-11DA-8605-000D9346EC2A}, Volume = {24}, Year = {2004}, url = {papers/Rappert_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2451-04.2004}} @article{Rasika:1999, Abstract = {New neurons are incorporated into the high vocal center (HVC), a nucleus of the adult canary (Serinus canaria) brain that plays a critical role in the acquisition and production of learned song. Recruitment of new neurons in the HVC is seasonally regulated and depends upon testosterone levels. We show here that brain-derived neurotrophic factor (BDNF) is present in the HVC of adult males but is not detectable in that of females, though the HVC of both sexes has BDNF receptors (TrkB). Testosterone treatment increases the levels of BDNF protein in the female HVC, and BDNF infused into the HVC of adult females triples the number of new neurons. Infusion of a neutralizing antibody to BDNF blocks the testosterone-induced increase in new neurons. Our results demonstrate that BDNF is involved in the regulation of neuronal replacement in the adult canary brain and suggest that the effects of testosterone are mediated through BDNF.}, Author = {Rasika, S. and Alvarez-Buylla, A. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Neuron}, Keywords = {C-8;Receptor, Ciliary Neurotrophic Factor;Testosterone/antagonists &inhibitors/*pharmacology;Cell Survival/drug effects;Female;Recruitment (Neurology)/physiology;Animal;Receptor Protein-Tyrosine Kinases/metabolism;Male;Vocalization, Animal/physiology;Canaries;Brain/cytology/metabolism/*physiology;Brain-Derived Neurotrophic Factor/immunology/metabolism/*pharmacology;Sex Characteristics;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Antibodies/pharmacology;Receptors, Nerve Growth Factor/metabolism;Neurons/*drug effects/physiology}, Number = {1}, Organization = {The Rockefeller University, New York, New York 10021, USA.}, Pages = {53-62.}, Title = {BDNF mediates the effects of testosterone on the survival of new neurons in an adult brain}, Uuid = {07CC7E48-D8CA-4BD5-A36F-6B0B57687E1F}, Volume = {22}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10027289}} @article{Rasika:1994, Abstract = {New neurons are added to the high vocal center (HVC) of adult male and female canaries. Exogenous testosterone induces a marked increase in HVC size in adult female canaries, though the mechanisms responsible for this increase remain unknown. To understand the mechanisms, we analyzed the effects of testosterone on neuronal recruitment in the female HVC. Intact adult female canaries received Silastic implants that were empty or filled with testosterone. Birds in the short- survival group received the Silastic implant, followed by a single injection of [3H]thymidine 2 days later, and were killed on the following day. Birds in the long-survival group were injected once a day for 5 days with [3H]thymidine and received the Silastic implant 20 and 40 days later. These birds were killed 60 days after the first injection of [3H]thymidine. The number of 3H-labeled ventricular zone cells above, rostral, or caudal to HVC was not affected by the hormone treatment in the short-survival birds, suggesting that testosterone did not affect neuronal production. However, the number of 3H-labeled HVC neurons that projected to robust nucleus of the archistriatum (RA) in the long-survival birds was three times greater in the hormone-treated than in the control group, though the total number of RA-projecting cells did not change significantly. Testosterone also induced an increase in the size of the HVC cells that project to RA. Thus, these experiments suggest that testosterone affects the recruitment and/or survival of newly generated RA-projecting HVC neurons but does not affect their production.}, Author = {Rasika, S. and Nottebohm, F. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {*Brain Mapping;Support, U.S. Gov't, P.H.S.;Female;Autoradiography;Thymidine/metabolism;Testosterone/*pharmacology;Animal;04 Adult neurogenesis factors;Canaries/*physiology;Tritium;Vocalization, Animal/*physiology;Cell Survival/drug effects;Neurons/cytology/drug effects/*physiology;Brain/cytology/drug effects/*physiology;C abstr}, Number = {17}, Organization = {Laboratory of Animal Behavior, Rockefeller University, New York, NY 10021.}, Pages = {7854-8.}, Title = {Testosterone increases the recruitment and/or survival of new high vocal center neurons in adult female canaries}, Uuid = {E2061B67-D7C3-40FC-A7DB-136D24FD39E9}, Volume = {91}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8058723}} @article{Rasin:2007, Abstract = {The polarity and adhesion of radial glial cells (RGCs), which function as progenitors and migrational guides for neurons, are critical for morphogenesis of the cerebral cortex. These characteristics largely depend on cadherin-based adherens junctions, which anchor apical end-feet of adjacent RGCs to each other at the ventricular surface. Here, we show that mouse numb and numb-like are required for maintaining radial glial adherens junctions. Numb accumulates in the apical end-feet, where it localizes to adherens junction-associated vesicles and interacts with cadherins. Numb and Numbl inactivation in RGCs decreases proper basolateral insertion of cadherins and disrupts adherens junctions and polarity, leading to progenitor dispersion and disorganized cortical lamination. Conversely, overexpression of Numb prolongs RGC polarization, in a cadherin-dependent manner, beyond the normal neurogenic period. Thus, by regulating RGC adhesion and polarity, Numb and Numbl are required for the tissue architecture of neurogenic niches and the cerebral cortex.}, Author = {Rasin, Mladen-Roko R. and Gazula, Valeswara-Rao R. and Breunig, Joshua J. and Kwan, Kenneth Y. and Johnson, Matthew B. and Liu-Chen, Susan and Li, Hua-Shun S. and Jan, Lily Yeh and Jan, Yuh-Nung N. and Rakic, Pasko and Sestan, Nenad}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Animals;RNA;Cells, Cultured;Humans;Electroporation;Cell Polarity;research support, non-u.s. gov't;In Situ Hybridization;Cadherins;Cell Adhesion;Endosomes;Mice, Knockout;Neurons;Neuroglia;Cerebral Ventricles;Blotting, Western;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Immunohistochemistry;Membrane Proteins;Microscopy, Electron;Nerve Tissue Proteins;Stem Cells}, Month = {7}, Nlm_Id = {9809671}, Number = {7}, Organization = {Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA.}, Pages = {819-27}, Pii = {nn1924}, Pubmed = {17589506}, Title = {Numb and Numbl are required for maintenance of cadherin-based adhesion and polarity of neural progenitors}, Uuid = {949DA7F0-26F5-4FD4-B9E7-08ED9B708A66}, Volume = {10}, Year = {2007}, url = {papers/Rasin_NatNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1924}} @article{Ravizza:2005, Abstract = {PURPOSE: We investigated the activation of microglia and astrocytes, induction of cytokines, and hippocampal neuronal damage, 4 and 24 h after kainic acid-induced status epilepticus (SE) in postnatal day (PN) 9, 15, and 21 rats. METHODS: Limbic seizures were induced by systemic injection of kainic acid. Glia activation and neuronal cell loss were studied by using immunocytochemistry and Western blot. Cytokine expression was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot quantification. RESULTS: After SE onset, hippocampal glia activation, cytokine expression, and neuronal damage are all age-dependent phenomena. In the hippocampus, neuronal injury occurs only when cytokines are induced in glia, and cytokine synthesis precedes the appearance of degenerating neurons. Neuronal injury is more pronounced when interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) are produced in addition to IL-1beta. CONCLUSIONS: This study shows that cytokine induction in rat brain after sustained seizures is age dependent, and it is associated with the appearance of cell injury.}, Author = {Ravizza, Teresa and Rizzi, Massimo and Perego, Carlo and Richichi, Cristina and Vel{\'\i}skov{\'a}, Jana and Mosh{\'e}, Solomon L. and De Simoni, M. Grazia and Vezzani, Annamaria}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Cytokines;Nerve Degeneration;Astrocytes;Animals;Rats;Tumor Necrosis Factor-alpha;Rats, Sprague-Dawley;Hippocampus;Kainic Acid;11 Glia;Disease Models, Animal;Male;Reverse Transcriptase Polymerase Chain Reaction;Status Epilepticus;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Blotting, Western;Neuroglia;Inflammation Mediators;Gliosis;Interleukin-6;Research Support, N.I.H., Extramural;Immunohistochemistry;Inflammation;Research Support, Non-U.S. Gov't}, Nlm_Id = {2983306R}, Organization = {Department of Neuroscience, Mario Negri Institute for Pharmacological Research, Milan, Italy. ravizza\@marionegri.it}, Pages = {113-7}, Pii = {EPI01006}, Pubmed = {15987264}, Title = {Inflammatory response and glia activation in developing rat hippocampus after status epilepticus}, Uuid = {0AE85ABD-BC2A-4DF4-A0DA-301F14D97956}, Volume = {46 Suppl 5}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1528-1167.2005.01006.x}} @article{Raymond:1995, Abstract = {Cerebral cortical dysgenesis (CD) is a heterogeneous disorder of cortical development and organization commonly associated with epilepsy, with a variety of subtypes. We reviewed the clinical, EEG and neuroimaging features in 100 adult patients with CD. There were 39 men and 61 women with a median age of 27 years (range 15-63 years). All patients were referred because of medically refractory epilepsy. Median age at seizure onset was 10 years (range 3 weeks to 39 years); in 30 patients, onset was in adulthood. The epilepsy was classified as generalized in 16 patients and localization-related in 84. Of the latter, the epileptic syndromes in decreasing frequency were frontal (32\%), temporal (31\%), parietal (14\%) and occipital (7\%). Only 15\%of patients had a history of status epilepticus. Prenatal/perinatal problems were reported in 32 patients but these were severe in only four: exposure to drugs (three) and infection (one) during the first trimester. Delayed developmental milestones were seen in 10\%, mental retardation in 9\%, additional congenital abnormalities in 4\%and neurological deficits in 14\%of patients. Diagnosis of CD was based on neuroimaging in 70, pathology in four and both methods in the remaining 26. The following subcategories were identified: agyria/diffuse macrogyria (four patients), focal macrogyria (16), focal polymicrogyria (one), focal macrogyria/polymicrogyria associated with a cleft (11), minor gyral abnormalities (seven), subependymal grey matter heterotopia (20), bilateral subcortical laminar grey matter heterotopia (eight), tuberous sclerosis (five), focal cortical dysplasia/microdysgenesis (seven) and dysembryoplastic neuroepithelial tumours (DNT) (21). Sixty-eight percent of patients had normal CT and 19 out of 36 patients had normal previous conventional MRI. MRI-based hippocampal volume measurements in 47 patients revealed ratios (smaller: larger hippocampus) of < 0.90 in 16, 0.90-0.94 in 14 and > or = 0.95 in 17 patients. EEGs were normal in only five patients. Alpha rhythm was preserved in 78 patients, including one patient with bilateral posterior macrogyria. Localized polymorphic slow activity was present in 43 patients. Five of 68 patients with focal/unilateral CD had only bilateral independent/synchronous spiking and 14 out of 32 with diffuse/bilateral CD only focal/unilateral spiking. In 60 patients with nondiffuse CD or with abnormal gyration or DNT, the epileptiform abnormalities were less extensive than coextensive with the lesion in 28, more extensive than and overlapped the lesion in 18 and remote from the lesion in five; nine patients did not have epileptiform abnormalities. There was poor correlation between the epileptic syndromes and EEG abnormalities and the location/extent of CD as defined by MRI and pathology.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Raymond, A. A. and Fish, D. R. and Sisodiya, S. M. and Alsanjari, N. and Stevens, J. M. and Shorvon, S. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0006-8950}, Journal = {Brain}, Keywords = {Glioma;10 Development;Magnetic Resonance Imaging;Child, Preschool;Humans;Treatment Outcome;Middle Aged;Tuberous Sclerosis;Diagnosis, Differential;Congenital Abnormalities;London;Female;Epilepsy;Infant;Child;Mental Retardation;Tomography, X-Ray Computed;review;Male;10 genetics malformation;Cerebral Cortex;Retrospective Studies;Ependyma;Adult;Infant, Newborn;24 Pubmed search results 2008;Choristoma;Electroencephalography;Adolescent}, Month = {6}, Nlm_Id = {0372537}, Organization = {Epilepsy Research Group, National Hospital for Neurology and Neurosurgery, London, UK.}, Pages = {629-60}, Pubmed = {7600083}, Title = {Abnormalities of gyration, heterotopias, tuberous sclerosis, focal cortical dysplasia, microdysgenesis, dysembryoplastic neuroepithelial tumour and dysgenesis of the archicortex in epilepsy. Clinical, EEG and neuroimaging features in 100 adult patients}, Uuid = {50136D41-4FE5-41AF-940E-DF1D120535A4}, Volume = {118 ( Pt 3)}, Year = {1995}, url = {papers/Raymond_Brain1995.pdf}} @article{Raza:2004, Abstract = {Alterations in hippocampal neuronal Ca(2+) and Ca(2+)-dependent systems have been implicated in mediating some of the long-term neuroplasticity changes associated with acquired epilepsy (AE). However, there are no studies in an animal model of AE that directly evaluate alterations in intracellular calcium concentration ([Ca(2+)](i)) and Ca(2+) homeostatic mechanisms (Ca(2+) dynamics) during the development of AE. In this study, Ca(2+) dynamics were evaluated in acutely isolated rat CA1 hippocampal, frontal, and occipital neurons in the pilocarpine model by using [Ca(2+)](i) imaging fluorescence microscopy during the injury (acute), epileptogenesis (latency), and chronic-epilepsy phases of the development of AE. Immediately after status epilepticus (SE), hippocampal neurons, but not frontal and occipital neurons, had significantly elevated [Ca(2+)](i) compared with saline-injected control animals. Hippocampal neuronal [Ca(2+)](i) remained markedly elevated during epileptogenesis and was still elevated indefinitely in the chronic-epilepsy phase but was not elevated in SE animals that did not develop AE. Inhibiting the increase in [Ca(2+)](i) during SE with the NMDA channel inhibitor MK801 was associated in all three phases of AE with inhibition of the changes in Ca(2+) dynamics and the development of AE. Ca(2+) homeostatic mechanisms in hippocampal neurons also were altered in the brain-injury, epileptogenesis, and chronic-epilepsy phases of AE. These results provide evidence that [Ca(2+)](i) and Ca(2+)-homeostatic mechanisms are significantly altered during the development of AE and suggest that altered Ca(2+) dynamics may play a role in the induction and maintenance of AE and underlie some of the neuroplasticity changes associated with the epileptic phenotype.}, Author = {Raza, Mohsin and Blair, Robert E. and Sombati, Sompong and Carter, Dawn S. and Deshpande, Laxmikant S. and DeLorenzo, Robert J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Epilepsy;Rats, Sprague-Dawley;21 Neurophysiology;Homeostasis;Hippocampus;Rats;Apoptosis;Research Support, U.S. Gov't, P.H.S.;21 Calcium imaging;Seizures;Calcium;Time Factors;Animals;Male;24 Pubmed search results 2008;Dizocilpine Maleate;Neurons}, Month = {12}, Nlm_Id = {7505876}, Number = {50}, Organization = {Departments of Neurology, Pharmacology and Toxicology, and Biochemistry and Molecular Biophysics, Virginia Commonwealth University School of Medicine, Richmond, VA 23298-0599, USA.}, Pages = {17522-7}, Pii = {0408155101}, Pubmed = {15583136}, Title = {Evidence that injury-induced changes in hippocampal neuronal calcium dynamics during epileptogenesis cause acquired epilepsy}, Uuid = {3A23DC76-48E1-4AED-8285-36739A7F2EE4}, Volume = {101}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0408155101}} @article{Rebsam:2008, Abstract = {A surprising new mechanism that regulates the plasticity of postnatal neurons is reported in this issue by Sugiyama et al. (2008). These authors show in mice that visual experience triggers cell-to-cell transfer of the homeoprotein Otx2 to cortical interneurons, where it promotes maturation of inhibitory neural circuitry and opens the critical period for plasticity in the visual cortex.}, Author = {Rebsam, Alexandra and Mason, Carol A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {Visual Cortex;Sensory Deprivation;Neuronal Plasticity;comment;Interneurons;Animals;Humans;Mice;Otx Transcription Factors;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0413066}, Number = {3}, Organization = {Department of Pathology and Cell Biology, Columbia University, College of Physicians and Surgeons, 630 W. 168(th) Street, 14-509 P&S Building, New York, NY 10032, USA. adr2111\@columbia.edu}, Pages = {386-7}, Pii = {S0092-8674(08)00949-5}, Pubmed = {18692461}, Title = {Otx2's incredible journey}, Uuid = {2A3A4048-30DB-45AF-8EB8-D195C2ABA1A8}, Volume = {134}, Year = {2008}, url = {papers/Rebsam_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.07.029}} @article{Rebsam:2005, Abstract = {In the mouse somatosensory cortex, thalamocortical axons (TCAs) corresponding to individual whiskers cluster into restricted barrel domains during the first days of life. If whiskers are lesioned before that time, the cortical space devoted to the afferents from the damaged whisker shrinks and becomes occupied by thalamocortical afferents from neighboring unlesioned whiskers. This plasticity ends by postnatal day 3 (P3) to P4 when barrels emerge. To test whether TCA development and lesion-induced plasticity are linked, we used monoamine oxidase A knock-out (MAOA-KO) mice in which normal TCA development is halted by an excess of serotonin. Normal TCA development can be restored when serotonin levels are lowered by parachlorophenylalanine (PCPA). By varying the time of PCPA administration, we found that barrel development can be reinitiated until P11, although the emergence of TCA clusters becomes gradually slower and less complete. In mice in which barrels emerge 3 d later than the normal schedule, at P6 instead of P3, we examined lesion-induced plasticity. We find a progressive decline of the lesion-induced plasticity and a closure at P3, similar to normal mice, showing that this plasticity is not influenced by an excess of serotonin levels. Thus, in MAOA-KO mice, the emergence of barrel patterning can be delayed without a concomitant delay in lesion-induced plasticity, and the cortical space devoted to one whisker representation cannot be modified by the periphery once patterning is imprinted in the subcortical relays. We conclude that the closure of the lesion-induced plasticity period in the barrelfield is probably not determined at the cortical level.}, Author = {Rebsam, Alexandra and Seif, Isabelle and Gaspar, Patricia}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;10 Structural plasticity}, Month = {1}, Nlm_Id = {8102140}, Number = {3}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U616, Universit{\'e} Paris VI H\^{o}pital Salp\^{e}tri\`{e}re, 75651 Paris cedex 13, France.}, Pages = {706-10}, Pii = {25/3/706}, Pubmed = {15659608}, Title = {Dissociating barrel development and lesion-induced plasticity in the mouse somatosensory cortex}, Uuid = {2A68570D-CA0A-437A-A828-8E22721B7BAD}, Volume = {25}, Year = {2005}, url = {papers/Rebsam_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4191-04.2005}} @article{Recchi:2006, Author = {Recchi, Chiara and Chavrier, Philippe}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {Animals;comment;ADP-Ribosylation Factors;Proteins;Models, Biological;Protein Transport;Vacuolar Proton-Translocating ATPases;Hydrogen-Ion Concentration;15 Retrovirus mechanism;11 Glia;23 Technique;news;GTPase-Activating Proteins;Endosomes;Endocytosis;Transport Vesicles;Mice;24 Pubmed search results 2008;15 PS VSVG receptor}, Month = {2}, Nlm_Id = {100890575}, Number = {2}, Pages = {107-9}, Pii = {ncb0206-107}, Pubmed = {16450005}, Title = {V-ATPase: a potential pH sensor}, Uuid = {4FA8EDA2-AA6E-4E7C-B75D-7C4BFB8E4A2F}, Volume = {8}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb0206-107}} @article{Redecker:1998a, Abstract = {Cortical dysplasias are frequently caused by excitotoxic brain damage due to hypoxia or ischemia during development. Ibotenate, a glutamatergic agonist, was injected in the neopallium of rat pups at day of birth. The resulting cytoarchitectonic pattern includes neuronal depopulation in deep cortical layers, sulcus formation, and molecular ectopias, mimicking human polymicrogyria and disorders of neuronal migration. These cortical dysplasias persist until adulthood, providing a rat model to investigate the long-term functional consequences of cortical malformations.}, Author = {Redecker, C. and Hagemann, G. and Witte, O. W. and Marret, S. and Evrard, P. and Gressens, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {10 Development;research support, non-u.s. gov't;Excitatory Amino Acid Agonists;Ibotenic Acid;Female;Rats;Rats, Wistar;Cell Count;Abnormalities, Drug-Induced;Animals, Newborn;10 genetics malformation;Animals;Male;Cerebral Cortex;24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {8908639}, Number = {1}, Organization = {Neurologische Klinik, Heinrich Heine Universit{\"a}t, D{\"u}sseldorf, Germany.}, Pages = {109-13}, Pii = {S0165380698000650}, Pubmed = {9706396}, Title = {Long-term evolution of excitotoxic cortical dysgenesis induced in the developing rat brain}, Uuid = {4EAB7B4D-49F3-434C-BCAF-62176AD1C83D}, Volume = {109}, Year = {1998}} @article{Redecker:1998, Abstract = {Malformations of cortical development are increasingly recognized in association with severe epileptic syndromes, neuropsychological disorders and mental retardation. Several clinical and experimental studies suggest that functional consequences of cortical dysplasias are not restricted to the area of the dysplastic lesion but also involve remote brain regions. In the present study cortical malformations were induced in newborn rats at day of birth by intracerebral injection of the glutamatergic agonist ibotenate. The resulting cytoarchitectonic lesion associates neuronal depopulation of deep cortical layers, ectopic neurons in superficial layers and sulcus formation, mimicking human polymicrogyria and migration disorders. Electrophysiological recordings of evoked field potentials in slice preparations of adult animals reveal hyperexcitability in widespread cortical regions surrounding the dysplasia. Low-intensity stimulation induced epileptiform activity consisting of long-lasting, multiphasic and N-methyl-D-aspartate-dependent field responses. They appeared with high variability as all-or-none events. These widespread changes in excitability were not observed in sham-operated animals with small superficial ectopias but intact deep cortical layers, indicating that focal loss of these layers induces extended alterations in cortical connectivity and imbalance of excitation and inhibition. Restricted zones of increased excitability were also found in the forelimb and hindlimb representation cortex in sham-operated and control animals, demonstrating that this activity has to be considered as an intrinsic property of specific cortical areas. Deoxyglucose autoradiography showed that the widespread hyperexcitability in ibotenate-injected animals was not accompanied by alterations in glucose metabolism, although in the area of structural abnormality a typical metabolic pattern was found, revealing an increased glucose uptake in layer I. Hypometabolism as described for many types of human dysplastic lesions was not observed. This difference between the experimental and clinical data may be due to the absence of behavioral seizures in this model. However, it can be hypothesized that in patients with developmental malformations, additional pathogenic factors contribute to the manifestation of seizure disorders.}, Author = {Redecker, C. and Lutzenburg, M. and Gressens, P. and Evrard, P. and Witte, O. W. and Hagemann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Electric Stimulation;Animals;In Vitro;Rats;21 Epilepsy;Epilepsy;21 Dysplasia-heterotopia;Rats, Wistar;Glucose;Ibotenic Acid;Disease Models, Animal;Animals, Newborn;Cerebral Cortex;21 Neurophysiology;Immunohistochemistry;Autoradiography;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {99040817}, Nlm_Id = {9110718}, Number = {7}, Organization = {Neurologische Klinik, Heinrich-Heine-Universit{\"a}t, D{\"u}sseldorf, Germany.}, Pages = {623-34}, Pubmed = {9823483}, Title = {Excitability changes and glucose metabolism in experimentally induced focal cortical dysplasias}, Uuid = {97F42292-013D-11DB-9E68-000D9346EC2A}, Volume = {8}, Year = {1998}} @article{Redecker:2005, Abstract = {Electrophysiological studies of human cortical dysplasia and rodent models revealed widespread hyperexcitability in the malformation itself as well as in its vicinity. We here analyzed the initiation of paroxysmal epileptiform activity using optical imaging of neuronal activity in rats with cortical malformations induced by neonatal freeze lesions. Brain slice preparations were incubated with the voltage-sensitive dye RH795 and neuronal activity was monitored using a fast-imaging photodiode array combined with standard field potential recordings. Spontaneous paroxysmal epileptiform activity emerged in all slices from animals with cortical malformations and sham-operated controls 20-40 min after omission of extracellular Mg(2+). Following electrophysiological and optical recordings, slices were histochemically processed. Using this approach, the present study demonstrated that in animals with freeze-lesion-induced focal cortical malformations, paroxysmal epileptiform activity always emerged from the dysplastic cortex and then spread to adjacent areas through superficial layers. This distribution of initiation sites was significantly different to sham-operated controls in which epileptogenic foci were located in various cytoarchitectonic areas. The present study indicates that following global changes in excitability, the dysplastic cortex itself is the main initiation site of paroxysmal epileptiform activity in animals with focal cortical malformations.}, Author = {Redecker, Christoph and Hagemann, Georg and K{\"o}hling, R{\"u}diger and Straub, Heidrun and Witte, Otto W. and Speckmann, Erwin-Josef J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Microscopy, Interference;Electric Stimulation;Animals;In Vitro;Evoked Potentials;Rats;Comparative Study;21 Epilepsy;Epilepsy;Rats, Wistar;Disease Models, Animal;Time Factors;Animals, Newborn;Nervous System Malformations;Cerebral Cortex;21 Neurophysiology;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Neurology, Friedrich Schiller University, Erlanger Allee 101, D-07747 Jena, Germany. redecker\@med.uni-jena.de}, Pages = {288-98}, Pii = {S0014-4886(04)00437-6}, Pubmed = {15755546}, Title = {Optical imaging of epileptiform activity in experimentally induced cortical malformations}, Uuid = {B627400A-5040-48A5-AA3B-3110F4807EA2}, Volume = {192}, Year = {2005}, url = {papers/Redecker_ExpNeurol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2004.11.018}} @article{Redecker:2000, Abstract = {Focal cortical malformations comprise a heterogeneous group of disturbances of brain development, commonly associated with drug-resistant epilepsy and/or neuropsychological deficits. Electrophysiological studies on rodent models of cortical malformations demonstrated intrinsic hyperexcitability in the lesion and the structurally intact surround, indicating widespread imbalances of excitation and inhibition. Here, alterations in regional expression of GABA(A) receptor subunits were investigated immunohistochemically in adult rats with focal cortical malformations attributable to neonatal freeze-lesions. These lesions are morphologically characterized by a three- to four-layered cortex with microsulcus formation. Widespread regionally differential reduction of GABA(A) receptor subunits alpha1, alpha2, alpha3, alpha5, and gamma2 was observed. Within the cortical malformation, this downregulation was most prominent for subunits alpha5 and gamma2, whereas medial to the lesion, a significant and even stronger decrease of all subunits was detected. Lateral to the dysplastic cortex, the decrease was most prominent for subunit gamma2 and moderate for subunits alpha1, alpha2, and alpha5, whereas subunit alpha3 was not consistently altered. Interestingly, the downregulation of GABA(A) receptor subunits also involved the ipsilateral hippocampal formation, as well as restricted contralateral neocortical areas, indicating widespread disturbances in the neocortical and hippocampal network. The described pattern of downregulation of GABA(A) receptor subunits allows the conclusion that there is a considerable modulation of subunit composition. Because alterations in subunit composition critically influence the electrophysiological and pharmacological properties of GABA(A) receptors, these alterations might contribute to the widespread hyperexcitability and help to explain pharmacotherapeutic characteristics in epileptic patients.}, Author = {Redecker, C. and Luhmann, H. J. and Hagemann, G. and Fritschy, J. M. and Witte, O. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Organ Specificity;Down-Regulation;Epilepsies, Partial;Research Support, Non-U.S. Gov't;Brain;21 Neurophysiology;24 Pubmed search results 2008;Rats;21 Epilepsy;Rats, Wistar;Animals, Newborn;Necrosis;Animals;Disease Models, Animal;Cerebral Cortex;Freezing;Receptors, GABA-A}, Medline = {20325152}, Month = {7}, Nlm_Id = {8102140}, Number = {13}, Organization = {Department of Neurology and Institute of Neurophysiology, Heinrich-Heine-University, D-40225 D{\"u}sseldorf, Germany.}, Pages = {5045-53}, Pii = {20/13/5045}, Pubmed = {10864962}, Title = {Differential downregulation of GABAA receptor subunits in widespread brain regions in the freeze-lesion model of focal cortical malformations}, Uuid = {D7429F00-CDD9-4A81-8F7E-21D34CA2C30D}, Volume = {20}, Year = {2000}} @article{Redmond:1996, Abstract = {In the mammalian brain, an important phase of neurogenesis occurs postnatally in the subventricular zone (SVZ). This region consists of a heterogeneous population of cells, some mitotically active, others postmitotic. A subset of mitotically active SVZ precursor cells gives rise to a population of neurons that migrates over a long distance to their final destination, the olfactory bulb. Other SVZ precursor cells continue to proliferate or undergo cell death. The combination of genes that regulates proliferation and cell fate determination of SVZ precursor cells remains to be identified. We have used the rat homolog of the human homeobox gene PBX1 in Northern analysis and in situ hybridization studies to determine the temporal and regional localization of PBX1 expression during embryonic and postnatal rat brain development. PBX1 is expressed embryonically in the telencephalon. In addition, it is expressed at high levels postnatally in the SVZ, in the migratory pathway to the olfactory bulb, and in the layers of the olfactory bulb that are the targets of these migratory neurons. Combining in situ hybridization for PBX1 with immunostaining for markers of cell proliferation (PCNA), postmitotic neurons (class III beta-tubulin), and glia (GFAP), we show that SVZ proliferating cells and their neuronal progeny express rat PBX1 mRNA, whereas glial cells do not express detectable levels of PBX1. The expression of PBX1 in SVZ precursor cells and postmitotic neurons suggests a role for PBX1 in the generation of olfactory bulb interneurons and in mammalian neurogenesis.}, Author = {Redmond, L. and Hockfield, S. and Morabito, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci}, Keywords = {Tubulin/metabolism;Cerebral Ventricles/*physiology;Gene Expression Regulation;Base Sequence;Oligonucleotides, Antisense/genetics;Rats;Oligonucleotide Probes/genetics;Stem Cells/physiology;*Gene Expression;Aging/physiology;Animal;C abstr;Neural Pathways/physiology;Olfactory Bulb/cytology/*physiology;Animals, Newborn/*physiology;*Genes, Homeobox;04 Adult neurogenesis factors;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;RNA, Messenger/metabolism;Molecular Sequence Data;Interneurons/*physiology}, Number = {9}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8066, USA.}, Pages = {2972-82.}, Title = {The divergent homeobox gene PBX1 is expressed in the postnatal subventricular zone and interneurons of the olfactory bulb}, Uuid = {B9624345-5EC5-4BC7-A883-BE0AEAD8C198}, Volume = {16}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8622127}} @article{Reep:1999, Abstract = {Fluorescent axonal tracers were used to investigate the connections of medial agranular cortex (frontal area 2, Fr2) in male prairie voles. The rostral and caudal portions of Fr2 (rFr2 and cFr2) have distinct but partially overlapping patterns of connections. Thalamic labeling after cFr2 injections was present in anteromedial nucleus (AM), ventrolateral nucleus (VL), lateral segment, mediodorsal nucleus (MDl), centrolateral nucleus (CL), ventromedial nucleus (VM), posterior nucleus (Po) and lateral posterior nucleus (LP). A band of labeled cells involving CL, central medial nucleus (CM) and rhomboid nucleus (Rh) formed a halo around the periphery of submedial (gelatinosus) nucleus (Sm). Within cFr2 there is a rostrocaudal gradient whereby projections from VL and MDl become progressively sparser caudally, whereas those from LP and Po become denser. Rostral Fr2 receives afferents from a similar group of thalamic nuclei, but has denser innervation from VL and MDl, lacks afferents from LP, and receives less input from nuclei around the periphery of Sm. Caudal Fr2 has extensive cortical connections including orbital cortex, rostral Fr2, Fr1, caudal parietal area 1 (Par1), parietal area 2 (Par2), and posterior parietal, retrosplenial and visual areas. Rostral Fr2 has similar connections with areas Fr1, Par1 and Par2; orbital connections focused in ventrolateral orbital cortex (VLO); connections with caudal Fr2; greatly reduced connections with posterior parietal cortex and the visual areas; and no connections with retrosplenial cortex. The axons linking rFr2 and cFr2 with each other and with other cortical areas travel predominately in the deep gray matter of layers VI and VII rather than in the white matter. Projections to the dorsal striatum from rFr2 are widespread in the head of the caudate, become progressively restricted to a dorsocentral focus more caudally, and disappear by the level of the anterior commissure. The projections from cFr2 are largely restricted to a focal dorsocentral region of the striatum and to the dorsolateral margin of the caudatoputamen. In comparison to area Fr2, the laterally adjacent area Fr1 has thalamic and cortical connections which are markedly restricted. Area Fr1 receives thalamic input from nuclei VL, anteroventral nucleus (AV), CL and Po, but none from mediodorsal nucleus (MD) or LP, and its input from VM is reduced. Cortical afferents to Fr1 originate from areas Fr2, caudal Par1 and Par2. Medial agranular cortex of prairie voles has a pattern of connections largely similar to that seen in rats, suggesting that area Fr2 in prairie voles is part of a cortical network that may mediate complex behaviors involving spatial orientation.}, Author = {Reep, R. L. and Kirkpatrick, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Thalamic Nuclei;Research Support, Non-U.S. Gov't;Neural Pathways;Brain Mapping;Prosencephalon;Male;Microtinae;Animals;24 Pubmed search results 2008;Frontal Lobe}, Medline = {99309992}, Month = {6}, Nlm_Id = {0043312}, Number = {3}, Organization = {Department of Physiological Sciences and Brain Institute, University of Florida, Gainesville 32610, USA. reep\@ufbi.ufl.edu}, Pages = {336-50}, Pubmed = {10382619}, Title = {Forebrain connections of medial agranular cortex in the prairie vole, Microtus ochrogaster}, Uuid = {900F6E24-BBB7-495B-9C84-2B1D4125CD26}, Volume = {126}, Year = {1999}} @article{Reeves:2006, Abstract = {Pattern formation in developing organisms can be regulated at a variety of levels, from gene sequence to anatomy. At this level of complexity, mechanistic models of development become essential for integrating data, guiding future experiments, and predicting the effects of genetic and physical perturbations. However, the formulation and analysis of quantitative models of development are limited by high levels of uncertainty in experimental measurements, a large number of both known and unknown system components, and the multiscale nature of development. At the same time, an expanding arsenal of experimental tools can constrain models and directly test their predictions, making the modeling efforts not only necessary, but feasible. Using a number of problems in fruit fly development, we discuss how models can be used to test the feasibility of proposed patterning mechanisms and characterize their systems-level properties.}, Author = {Reeves, Gregory T. and Muratov, Cyrill B. and Sch{\"u}pbach, Trudi and Shvartsman, Stanislav Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1534-5807}, Journal = {Dev Cell}, Keywords = {Models, Biological;24 Pubmed search results 2008;research support, n.i.h., extramural ;research support, non-u.s. gov't ;09 Evolutionary dynamics;Drosophila;research support, u.s. gov't, non-p.h.s. ;Body Patterning;Cell Polarity;Animals;Morphogenesis;Wing;review;Developmental Biology}, Month = {9}, Nlm_Id = {101120028}, Number = {3}, Organization = {Department of Chemical Engineering and Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08544, USA.}, Pages = {289-300}, Pii = {S1534-5807(06)00352-2}, Pubmed = {16950121}, Title = {Quantitative models of developmental pattern formation}, Uuid = {7202C0FF-8C89-41A9-9BA8-5A9F37EE8D66}, Volume = {11}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devcel.2006.08.006}} @article{Regehr:1994, Abstract = {Further characterization of the biochemical components that contribute to calcium handling, together with advances in optical imaging of ion concentration, are providing quantitative information on the dynamics of calcium in the dendrites of neurons in tissue culture, brain slices and in vivo. It has recently been demonstrated that strong spatial gradients and transient calcium elevations result from the geometry and membrane properties of dendrites. These studies are adding to our understanding of calcium's role in synaptic plasticity and in shaping the electrophysiological properties of neurons.}, Author = {Regehr, W. G. and Tank, D. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Purkinje Cells;Dendrites;21 Neurophysiology;Hippocampus;research support, non-u.s. gov't ;Pyramidal Cells;Calcium;Electrophysiology;Synaptic Transmission;Animals;Humans;24 Pubmed search results 2008;review}, Month = {6}, Nlm_Id = {9111376}, Number = {3}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115.}, Pages = {373-82}, Pubmed = {7919932}, Title = {Dendritic calcium dynamics}, Uuid = {162A3EE2-E80E-4859-81DC-49C4B740F76A}, Volume = {4}, Year = {1994}} @article{Regehr:1991, Abstract = {We describe a method for filling presynaptic terminals and cell dendrites in adult brain slices with the fluorescent calcium indicator fura-2 by localized perfusion of the acetoxymethyl (AM) ester derivative. The method provides labeling selectivity, similar to that produced by intracellular microinjection of fura-2, with the simplicity of bath application of membrane-permeant AM esters. Application of the method to mossy fiber tracts in hippocampal region CA3 and parallel fiber tracts in cerebellum resulted in distant presynaptic terminals well labelled with fura-2 without concomitant postsynaptic labelling, allowing optical measurements of calcium concentration in individual presynaptic terminals. Application of the method to CA1 pyramidal cells produced intracellular loading of apical dendrites with fura-2. Dendritic calcium changes produced by afferent fiber stimulation were similar to those determined from cells filled with fura-2 by intracellular microinjection. The method appears to be general, and should provide a means to fill projecting axons and dendritic processes in many areas of the brain with fluorescent indicators, allowing optical measurements of ion concentration dynamics to be performed in brain slice that were previously impractical.}, Author = {Regehr, W. G. and Tank, D. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Perfusion;21 Neurophysiology;Hippocampus;Guinea Pigs;in vitro ;Nerve Endings;Calcium;Fura-2;Animals;Brain;24 Pubmed search results 2008;Fluorescence}, Month = {4}, Nlm_Id = {7905558}, Number = {2}, Organization = {Biophysics Research Department, AT & T Bell Laboratories, Murray Hill, NJ 07974.}, Pages = {111-9}, Pii = {0165-0270(91)90121-F}, Pubmed = {1881195}, Title = {Selective fura-2 loading of presynaptic terminals and nerve cell processes by local perfusion in mammalian brain slice}, Uuid = {3CD78182-3583-4194-9565-743C449072BA}, Volume = {37}, Year = {1991}} @article{Regehr:1989, Abstract = {The dynamic response of nerve cells to synaptic activation and the spatial distribution of biochemical processes regulated by ion concentration are critically dependent on the cell-surface distribution of ion channels. In the hippocampus, intracellular calcium-ion concentration is thought to influence the biochemical events associated with kindling, excitotoxicity, and long-term potentiation. Computer models of hippocampal pyramidal cells also indicate that calcium-channel location influences dynamic characteristics such as bursting. Here, we have used in situ microfluorometric imaging in brain slices to directly measure the spatial distribution of calcium accumulation in guinea-pig CA1 pyramidal cells during trains of orthodromic synaptic stimulation. Calcium accumulation is substantial throughout the entire proximal section of the apical and basal dendrites. Most of this accumulation results from influx through non-NMDA (N-methyl-D-aspartate) voltage-gated calcium channels, and in the apical dendrite it drops steeply as the dendrite enters stratum moleculare, the termination zone of perforant path afferents. These results demonstrate a marked segregation of calcium-channel activity and directly show a spatial distribution of calcium accumulation during orthodromic synaptic activation.}, Author = {Regehr, W. G. and Connor, J. A. and Tank, D. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Synapses;Dendrites;21 Neurophysiology;Kinetics;Hippocampus;Guinea Pigs;in vitro ;Calcium;Pyramidal Tracts;Benzofurans;Fluorescent Dyes;Microscopy, Fluorescence;Fura-2;Animals;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {0410462}, Number = {6242}, Organization = {Molecular Biophysics Research Department, AT&T Bell Laboratories, Murray Hill, New Jersey 07974.}, Pages = {533-6}, Pubmed = {2797180}, Title = {Optical imaging of calcium accumulation in hippocampal pyramidal cells during synaptic activation}, Uuid = {6AFE6834-F26B-40C9-B37E-61104CEFEC6C}, Volume = {341}, Year = {1989}, url = {papers/Regehr_Nature1989.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/341533a0}} @article{Rehen:2005, Abstract = {The mouse brain contains genetically distinct cells that differ with respect to chromosome number manifested as aneuploidy (Rehen et al., 2001); however, the relevance to humans is not known. Here, using double-label fluorescence in situ hybridization for the autosome chromosome 21 (chromosome 21 point probes combined with chromosome 21 "paint" probes), along with immunocytochemistry and cell sorting, we present evidence for chromosome gain and loss in the human brain. Chromosome 21 aneuploid cells constitute approximately 4\%of the estimated one trillion cells in the human brain and include non-neuronal cells and postmitotic neurons identified by the neuronspecific nuclear protein marker. In comparison, human interphase lymphocytes present chromosome 21 aneuploidy rates of 0.6\%. Together, these data demonstrate that human brain cells (both neurons and non-neuronal cells) can be aneuploid and that the resulting genetic mosaicism is a normal feature of the human CNS.}, Author = {Rehen, Stevens K. and Yung, Yun C. and McCreight, Matthew P. and Kaushal, Dhruv and Yang, Amy H. and Almeida, Beatriz S. V. and Kingsbury, Marcy A. and Cabral, K{\'a}tia M. S. and McConnell, Michael J. and Anliker, Brigitte and Fontanoz, Marisa and Chun, Jerold}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {08 Aberrant cell cycle}, Month = {3}, Nlm_Id = {8102140}, Number = {9}, Organization = {Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037, USA.}, Pages = {2176-80}, Pii = {25/9/2176}, Pubmed = {15745943}, Title = {Constitutional aneuploidy in the normal human brain}, Uuid = {2707D202-1248-4214-A33E-7120D240FA04}, Volume = {25}, Year = {2005}, url = {papers/Rehen_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4560-04.2005}} @article{Rehen:2001, Abstract = {A basic assumption about the normal nervous system is that its neurons possess identical genomes. Here we present direct evidence for genomic variability, manifested as chromosomal aneuploidy, among developing and mature neurons. Analysis of mouse embryonic cerebral cortical neuroblasts in situ detected lagging chromosomes during mitosis, suggesting the normal generation of aneuploidy in these somatic cells. Spectral karyotype analysis identified approximately 33\%of neuroblasts as aneuploid. Most cells lacked one chromosome, whereas others showed hyperploidy, monosomy, and/or trisomy. The prevalence of aneuploidy was reduced by culturing cortical explants in medium containing fibroblast growth factor 2. Interphase fluorescence in situ hybridization on embryonic cortical cells supported the rate of aneuploidy observed by spectral karyotyping and detected aneuploidy in adult neurons. Our results demonstrate that genomes of developing and adult neurons can be different at the level of whole chromosomes. 0027-8424 Journal Article}, Author = {Rehen, S. K. and McConnell, M. J. and Kaushal, D. and Kingsbury, M. A. and Yang, A. H. and Chun, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Mice, Inbred BALB C;In Situ Hybridization, Fluorescence;Interphase;Animals;*Variation (Genetics);Neurons/*ultrastructure;Female;EE pdf;*Chromosomes;08 Aberrant cell cycle;Male;Aneuploidy;Support, Non-U.S. Gov't;Cerebral Cortex/*ultrastructure;Karyotyping;Flow Cytometry;Support, U.S. Gov't, P.H.S.;Mice;Immunohistochemistry}, Number = {23}, Organization = {Department of Pharmacology, School of Medicine, University of California, San Diego, CA 92093-0636, USA.}, Pages = {13361-6}, Title = {Chromosomal variation in neurons of the developing and adult mammalian nervous system}, Uuid = {03BA246E-ABCF-4510-B214-2D424CBE6101}, Volume = {98}, Year = {2001}, url = {papers/Rehen_ProcNatlAcadSciUSA2001.pdf}} @article{Reichert:2001, Abstract = {The removal of damaged myelin is central to repair after injury to axons and in autoimmune demyelinating diseases. Complement receptor 3 (CR3/MAC-1) plays a major role in mediating the phagocytosis of damaged myelin by macrophages and microglia. We studied the modulation (inhibition and augmentation) of CR3/MAC-1 mediated myelin phagocytosis by mAbs that bind to distinct epitopes of subunits alphaM and beta2 of CR3/MAC-1. mAb M1/70 anti-alpha(M) and mAb 5C6 anti-alpha(M) inhibited, whereas mAb M18/2 anti-beta2 augmented myelin phagocytosis. This mAb-induced modulation of myelin phagocytosis occurred in the presence and absence of active complement. Inhibition induced by M1/70 or 5C6 did not add when the two were combined. Combining M1/70 or 5C6 with M18/2 reduced the augmentation induced by M18/2 alone. CR3/MAC-1-mediated myelin phagocytosis may thus be subjected to modulation between efficient and inefficient functional/activation states. These observations and conclusions may offer an explanation for the observed discrepancy between efficient myelin phagocytosis in experimental allergic encephalomyelitis and inefficient myelin phagocytosis after injury to CNS axons, although in both instances macrophages/microglia express CR3/MAC-1.}, Author = {Reichert, F. and Slobodov, U. and Makranz, C. and Rotshenker, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0969-9961}, Journal = {Neurobiol Dis}, Keywords = {Nerve Regeneration;Antibodies, Monoclonal;Macrophage-1 Antigen;Mice, Inbred C57BL;Myelin Sheath;Not relevant;Epitopes;11 Glia;Macrophages;Mice;Support, Non-U.S. Gov't;Phagocytosis;Male;Animals}, Medline = {21337051}, Month = {6}, Nlm_Id = {9500169}, Number = {3}, Organization = {Department of Anatomy &Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.}, Pages = {504-12}, Pii = {S0969996101903833}, Pubmed = {11442357}, Title = {Modulation (inhibition and augmentation) of complement receptor-3-mediated myelin phagocytosis}, Uuid = {467899AE-146E-42C7-B759-9DD7DA16AD47}, Volume = {8}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/nbdi.2001.0383}} @article{Reid:1997, Abstract = {Cell lineage analysis with retroviral libraries suggests that clonal progeny disperse widely in rodent cortex. To determine whether widespread dispersion is a general mammalian plan and to investigate phylogenetic differences in cortical development, we analyzed cell lineage in the ferret, a carnivore and near relative of the cat. The ferret possesses a highly developed, folded cerebral cortex, characteristic of higher mammalian species. Progenitor cells of the ferret cerebral cortex were tagged with an amphotropic retroviral library encoding alkaline phosphatase, and sibling relationships were determined using the polymerase chain reaction. Neuronal clones were single neurons (52\%) or large clones (48\%; average, 7 neurons) containing neurons and glia in widespread cortical locations. Neuronal clones in the ferret labeled at middle to late neurogenesis (embryonic day 33-35) contained large numbers of neurons and showed little tendency to cluster. The large proportion of single neuron clones, contrasted with the large size of multicell clones, suggests that some progenitors divide asymmetrically, producing a postmitotic neuron and regenerating a multipotential cell.}, Author = {Reid, C. B. and Tavazoie, S. F. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {10 Development;Cell Differentiation;Embryonic Induction;Animals;Ferrets;Pregnancy;Phenotype;research support, u.s. gov't, p.h.s. ;Models, Biological;Female;Staining and Labeling;Retroviridae;Alkaline Phosphatase;research support, non-u.s. gov't ;Cerebral Cortex;Neurons;Polymerase Chain Reaction;Cell Division;24 Pubmed search results 2008;Stem Cells;Clone Cells;Gestational Age}, Month = {6}, Nlm_Id = {8701744}, Number = {12}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, MA 02115, USA.}, Pages = {2441-50}, Pubmed = {9199370}, Title = {Clonal dispersion and evidence for asymmetric cell division in ferret cortex}, Uuid = {4D2D807A-FABD-4C76-B2A1-4C78DE06034B}, Volume = {124}, Year = {1997}, url = {papers/Reid_Development1997.pdf}} @article{Reid:1999, Abstract = {To understand the clonal relationship of various olfactory bulb (OB) cell types, OB progenitor cells were infected at embryonic day (E) 14, E15, and E17 with retroviral libraries encoding alkaline phosphatase or beta-galactosidase. After survival to postnatal day 10-15, sibling relationships were identified by polymerase chain reaction DNA amplification of distinct sequences in the retroviral constructs. Within the OB, clonal progeny dispersed widely in all directions. In sharp contrast, however, clonal dispersion between the OB and neocortex was not observed, although occasional clonal dispersion between the OB and pyriform and hippocampal regions could not be excluded. Most clones (84\%) contained a single cell type, especially after E17 injections, suggesting the existence of either restricted precursors, or multipotential progenitors instructed by a restricted cellular environment. Mixed OB clones (16\%) contained multiple cell types in the OB, or occasionally glial or neuronal cells outside the OB, demonstrating the existence of multipotential OB progenitors, likely at a stage before formation of the olfactory rostral migratory stream. Surprisingly, OB glial cells were not labeled, suggesting distinct lineages or perhaps distinct migratory paths for glia and neurons into the OB. A hierarchical cell lineage is proposed that involves a multipotential progenitor that gives rise to potentially more limited progenitors.}, Author = {Reid, C. B. and Liang, I. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {J Comp Neurol}, Keywords = {Fetal Development/physiology;Neuroglia/cytology/physiology;Neurons/cytology/physiology;13 Olfactory bulb anatomy;Rats, Long-Evans;Rats;Cell Line;Prosencephalon/embryology;I pdf;Animal;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Olfactory Bulb/*embryology;Polymerase Chain Reaction;Embryo/cytology/physiology;Cell Movement/physiology}, Number = {1}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {106-18.}, Title = {Clonal mixing, clonal restriction, and specification of cell types in the developing rat olfactory bulb}, Uuid = {C434B816-DC7A-4E08-8324-E03DC4E04626}, Volume = {403}, Year = {1999}, url = {papers/Reid_JCompNeurol1999}} @article{Reiner:1993, Abstract = {Telencephalic cortex in turtles is a simple three layered-structure. The dorsal most part of this structure is thought to resemble the reptilian forerunner of at least parts of mammalian isocortex. This dorsal part of turtle cortex contains several functionally distinct regions that show similarity in their connections and function to specific areas in mammalian isocortex. The types of neurons found in turtle dorsal cortex (as defined by their morphology and neurotransmitter content) also show great similarity to those observed in mammals, with the major exception that turtle cortex appears to lack the types of neurons found in granular and supragranular layers of mammalian isocortex. Similar results have also been observed in other living reptiles. Thus, one major step in the evolution of reptilian cortex into mammalian cortex must have been the addition of the types of neurons found in the granular and supragranular layers of mammalian isocortex. These observations for turtles also suggest that turtle cortex in particular and reptilian telencephalic cortex in general must differ functionally from mammalian isocortex with respect to those features associated with the laminar and columnar organization of isocortex. These issues are discussed in more detail below and in Reiner (1991). Journal Article Review Review, Tutorial}, Author = {Reiner, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Comp Biochem Physiol Comp Physiol}, Keywords = {Cerebral Cortex/cytology/*physiology;Human;Turtles/*physiology;Neural Pathways/cytology/physiology;Support, U.S. Gov't, P.H.S.;N;Neurotransmitters/*physiology;Animals;*Evolution;19 Neocortical evolution}, Number = {4}, Organization = {Department of Anatomy and Neurobiology, University of Tennessee-Memphis 38163.}, Pages = {735-48}, Pubmed = {8097979}, Title = {Neurotransmitter organization and connections of turtle cortex: implications for the evolution of mammalian isocortex}, Uuid = {252A29D3-D7BE-4962-9198-EF62E228C4B7}, Volume = {104}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8097979}} @article{Reisman:1989, Abstract = {Transcription from the Moloney murine leukemia virus (Mo-MuLV) long terminal repeat (LTR) is inhibited in murine stem cells and induced during maturation of these cells. We have investigated whether alterations in the activity of this viral regulatory element also occur during differentiation of human myeloid leukemia cells. The Mo-MuLV LTR and the simian virus 40 (SV40) early promoter were introduced into HL-60 promyelocytes on Epstein-Barr virus-derived chloramphenicol acetyltransferase expression vectors. When these cells were induced to terminally differentiate, transcription from the Mo-MuLV LTR was induced approximately 10-fold. Expression from the SV40 promoter remained constant during differentiation of these cells. Replacing the SV40 transcriptional enhancer with the Mo-MuLV LTR transcriptional enhancer rendered the SV40 promoter inducible during differentiation. We conclude that sequences within the transcriptional enhancer of the Mo-MuLV LTR contain cis-acting elements responsible for induction of gene expression during differentiation of human myeloid cells. 0270-7306 Journal Article}, Author = {Reisman, D. and Rotter, V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Mol Cell Biol}, Keywords = {Cell Differentiation;RNA/analysis;Human;EE, DMSO, abstr;Cell Line;Gene Expression Regulation;Promoter Regions (Genetics);08 Aberrant cell cycle;Chloramphenicol O-Acetyltransferase/genetics;Moloney murine leukemia virus/*genetics;Dimethyl Sulfoxide/pharmacology;*Enhancer Elements (Genetics);Simian virus 40/genetics;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Granulocytes/*metabolism;Genetic Vectors}, Number = {8}, Organization = {Department of Cell Biology, Weizmann Institute of Science, Rehovot, Israel.}, Pages = {3571-5}, Pubmed = {2477690}, Title = {Induced expression from the Moloney murine leukemia virus long terminal repeat during differentiation of human myeloid cells is mediated through its transcriptional enhancer}, Uuid = {60822156-EF26-4B76-AF5A-57815EEB760F}, Volume = {9}, Year = {1989}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2477690}} @article{Reiss:2007, Abstract = {It has been hypothesized that phenotypic variation in mammals could in part be due to incomplete and variable silencing of retrotransposons in somatic cells. This theory is based on the fact that some recent endogenous retroviral (ERV) insertions in the mouse exert variable effects on genes in isogenic animals, depending on the variable state of ERV methylation. In this article, we review the evidence for this and related phenomena and suggest that such stochastic epigenetic silencing is restricted to very recent insertions. We also present a model to explain the acquisition of a more stable epigenetic state for transposable element insertions through time.}, Author = {Reiss, Daphne and Mager, Dixie L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0378-1119}, Journal = {Gene}, Keywords = {DNA Methylation;Endogenous Retroviruses;Epigenesis, Genetic;research support, non-u.s. gov't;Retroelements;24 Pubmed search results 2008;Selection (Genetics);Stochastic Processes;Gene Silencing;Evolution, Molecular;Time Factors;Models, Genetic;Animals;Genomic Instability;Humans;review;Mice}, Month = {4}, Nlm_Id = {7706761}, Number = {1-2}, Organization = {Terry Fox Laboratory, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia, Canada V5Z1L3.}, Pages = {130-5}, Pii = {S0378-1119(06)00504-X}, Pubmed = {16987613}, Title = {Stochastic epigenetic silencing of retrotransposons: does stability come with age?}, Uuid = {9D089468-C51F-4CE8-A891-50E575AF7512}, Volume = {390}, Year = {2007}, url = {papers/Reiss_Gene2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.gene.2006.07.032}} @article{Remler:1973, Author = {Remler, M. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0010-5678}, Journal = {Confin Neurol}, Keywords = {Epilepsy;Penicillins;Electroencephalography;21 Epilepsy;24 Pubmed search results 2008;21 Neurophysiology;Blood-Brain Barrier;Cats;Dose-Response Relationship, Drug;Disease Models, Animal;Brain;Cerebral Cortex;Radiation Injuries, Experimental;Animals}, Medline = {73156190}, Nlm_Id = {7600680}, Number = {1}, Pages = {50-62}, Pubmed = {4697282}, Title = {Focal stimulation of the brain by entirely extracranial means. An example of radiation controlled focal pharmacology}, Uuid = {0C0249B6-09F8-4A14-88E8-EA0FD90171E1}, Volume = {35}, Year = {1973}} @article{Represa:2005, Abstract = {During brain development, transmitter-gated receptors are operative before synapse formation, suggesting that their action is not restricted to synaptic transmission. GABA, which is the principal excitatory transmitter in the developing brain, acts as an epigenetic factor to control processes including cell proliferation, neuroblast migration and dendritic maturation. These effects appear to be mediated through a paracrine, diffuse, non-synaptic mode of action that precedes the more focused, rapid mode of operation characteristic of synaptic connections. This sequential operation implies that GABA is used as an informative agent but in a unique context at an early developmental stage. This sequence also implies that by altering these effects, drugs acting on the GABA system could be pathogenic during pregnancy.}, Author = {Represa, Alfonso and Ben-Ari, Yehezkel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Synapses;21 Epilepsy;Cell Differentiation;21 Neurophysiology;Cell Proliferation;Neural Inhibition;gamma-Aminobutyric Acid;Animals;Brain;24 Pubmed search results 2008;Neurons;review}, Month = {6}, Nlm_Id = {7808616}, Number = {6}, Organization = {INMED/INSERM U29, Parc Scientifique et Technologique de Luminy, Marseille, France. represa\@inmed.univ-mrs.fr}, Pages = {278-83}, Pii = {S0166-2236(05)00083-4}, Pubmed = {15927682}, Title = {Trophic actions of GABA on neuronal development}, Uuid = {E6152F5A-E811-43E1-BD45-C43670F880E2}, Volume = {28}, Year = {2005}, url = {papers/Represa_TrendsNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2005.03.010}} @article{Restrepo:2003, Abstract = {Unilateral lesions of the occipital visual areas performed on postnatal day 5 (P5) in the ferret are not compensated by the appearance, in the lesioned hemisphere, of visual responses at ectopic locations. Instead, when parts of the visual areas are spared, they show abnormal retinotopic organizations; furthermore, callosal connections are abnormally distributed in relation to the retinotopic maps. Lesions that completely eliminate the visual areas including the posterior parietal cortex cause the appearance of abnormal callosal connections from the primary somatosensory cortex on the lesion side to the contralateral, intact, posterior parietal cortex. The occipital visual areas (17, 18, 19, and 21) of the intact hemisphere show a normal retinotopy but lose callosal connections in territories homotopic to the lesions. These findings clarify the nature and limits of structural developmental plasticity in the visual cortex. Early in life, certain regions of cortex have been irreversibly allocated to the visual areas, but two properties defining the areas, that is, retinotopy and connections, remain modifiable. The findings might be relevant for understanding the consequences of early-onset visual cortical lesions in humans.}, Author = {Restrepo, C. Ernesto and Manger, Paul R. and Spenger, Christian and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {Laterality;Retina;Visual Cortex;Magnetic Resonance Imaging;Neural Pathways;Not relevant;Ferrets;Occipital Lobe;11 Glia;Parietal Lobe;Animals, Newborn;Somatosensory Cortex;Support, Non-U.S. Gov't;Animals;Brain Mapping;Neurons;Corpus Callosum}, Medline = {22721294}, Month = {7}, Nlm_Id = {7707449}, Number = {1}, Organization = {Division of Neuroanatomy and Brain Development, Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. giorgio.innocenti\@neuro.ki.se}, Pages = {51-65}, Pubmed = {12838520}, Title = {Immature cortex lesions alter retinotopic maps and interhemispheric connections}, Uuid = {62D76F26-57B9-4645-B2E0-38616C6A4A29}, Volume = {54}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.10591}} @article{Restrepo:2002, Abstract = {Extensive lesions of the occipital cortex comprising the developing occipital visual areas and beyond in young ferrets (postnatal day 5) are followed by massive, but incomplete, degeneration of the lateral geniculate (LGN) and lateralis posterior (LP) nuclei of the thalamus, and minor volumetric reduction of the superior colliculus. Retinal projections (revealed by intraocular tracer injections), while reduced, remain confined to their territories of normal termination, both in the adult and throughout development. Comparisons with other mammalian species point to several common features in the developmental plasticity of retinofugal pathway.}, Author = {Restrepo, C. Ernesto and Manger, Paul R. and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Visual Cortex;Superior Colliculus;Nerve Degeneration;Comparative Study;Geniculate Bodies;Neuronal Plasticity;Not relevant;Ferrets;11 Glia;Animals, Newborn;Animals;Support, Non-U.S. Gov't;Visual Pathways}, Medline = {22318910}, Month = {11}, Nlm_Id = {8918110}, Number = {9}, Organization = {Division of Neuroanatomy and Brain Development, Department of Neuroscience, Karolinska Institutet, S-17177, Stockholm, Sweden.}, Pages = {1713-9}, Pii = {2246}, Pubmed = {12431224}, Title = {Retinofugal projections following early lesions of the visual cortex in the ferret}, Uuid = {CF5FE5FE-9326-4E92-B607-4D2AA62AFAFA}, Volume = {16}, Year = {2002}} @article{Reya:2001, Abstract = {Stem cell biology has come of age. Unequivocal proof that stem cells exist in the haematopoietic system has given way to the prospective isolation of several tissue-specific stem and progenitor cells, the initial delineation of their properties and expressed genetic programmes, and the beginnings of their utility in regenerative medicine. Perhaps the most important and useful property of stem cells is that of self-renewal. Through this property, striking parallels can be found between stem cells and cancer cells: tumours may often originate from the transformation of normal stem cells, similar signalling pathways may regulate self-renewal in stem cells and cancer cells, and cancer cells may include 'cancer stem cells'- rare cells with indefinite potential for self-renewal that drive tumorigenesis. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Reya, T. and Morrison, S. J. and Clarke, M. F. and Weissman, I. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Nature}, Keywords = {Mutation;F abstr;10 Development;Cell Transformation, Neoplastic;Hematopoietic Stem Cells;Human;Leukemia/pathology;Signal Transduction;Cell Division;Regeneration;*Stem Cells;Neoplasms/*pathology;Animals}, Number = {6859}, Organization = {Departments of Pathology and Developmental Biology, Stanford University School of Medicine, Palo Alto, California 94305, USA. irv\@stanford.edu}, Pages = {105-11}, Pubmed = {11689955}, Title = {Stem cells, cancer, and cancer stem cells}, Uuid = {8ECE38A0-C9CC-4CB3-830E-A47656F71300}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689955}} @article{Reynolds:1992, Abstract = {Neurogenesis in the mammalian central nervous system is believed to end in the period just after birth; in the mouse striatum no new neurons are produced after the first few days after birth. In this study, cells isolated from the striatum of the adult mouse brain were induced to proliferate in vitro by epidermal growth factor. The proliferating cells initially expressed nestin, an intermediate filament found in neuroepithelial stem cells, and subsequently developed the morphology and antigenic properties of neurons and astrocytes. Newly generated cells with neuronal morphology were immunoreactive for gamma-aminobutyric acid and substance P, two neurotransmitters of the adult striatum in vivo. Thus, cells of the adult mouse striatum have the capacity to divide and differentiate into neurons and astrocytes. 92205351 0036-8075 Journal Article}, Author = {Reynolds, B. A. and Weiss, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {Science}, Keywords = {Glial Fibrillary Acidic Protein/metabolism;Culture Media, Serum-Free;In Vitro;Astrocytes/*cytology;Fluorescent Antibody Technique;B-2;Neurons/*cytology;Cell Survival/drug effects;Cells, Cultured;Intermediate Filaments/metabolism;Animal;02 Adult neurogenesis migration;Corpus Striatum/*cytology;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;Intermediate Filament Proteins/metabolism;Mice;Phosphopyruvate Hydratase/metabolism;Cell Division/drug effects}, Number = {5052}, Organization = {Department of Pathology, University of Calgary Faculty of Medicine, Alberta, Canada.}, Pages = {1707-10}, Title = {Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system}, Uuid = {9B592C38-0B59-4B73-8852-43C4B205E3C3}, Volume = {255}, Year = {1992}, url = {papers/Reynolds_Science1992.pdf}} @article{Rezaie:1997, Author = {Rezaie, P. and Male, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0300-5127}, Journal = {Biochem Soc Trans}, Keywords = {Gestational Age;Intercellular Adhesion Molecule-1;Research Support, Non-U.S. Gov't;Fetus;Cell Adhesion Molecules;Vascular Cell Adhesion Molecule-1;Antigens, CD31;P-Selectin;Antigens, CD;11 Glia;Microglia;Macrophages;Cerebrovascular Circulation;Humans;Cerebral Cortex;Corpus Callosum}, Medline = {97334547}, Month = {5}, Nlm_Id = {7506897}, Number = {2}, Organization = {Department of Neuropathology, Institute of Psychiatry, London.}, Pages = {170S}, Pubmed = {9191214}, Title = {Expression of adhesion molecules on human foetal cerebral vessels: relationship to colonisation by microglial precursors}, Uuid = {7C8DABEF-19CE-4217-9413-A373EEFB89E0}, Volume = {25}, Year = {1997}} @article{Rezaie:2001, Abstract = {Alterations in the phenotype and function of microglia, the resident mononuclear phagocytes of the central nervous system, are among the earliest indications of pathology within the brain and spinal cord. The prion diseases, also known as spongiform encephalopathies, are fatal neurodegenerative disorders with sporadic, genetic or acquired infectious manifestations. A hallmark of all prion diseases is the aberrant metabolism and resulting accumulation of the prion protein. Conversion of the normal cellular protein [PrP(c)] into the abnormal pathogenic (or disease-causing) isoform [PrP(Sc)] involves a conformational alteration whereby the alpha-helical content is transformed into beta-sheet. The histological characteristics of these disorders are spongiform change, astrocytosis, neuronal loss and progressive accumulation of the protease-resistant prion isoform. An additional upregulation in microglial response has been reported in Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Str{\"a}ussler-Scheinker syndrome (GSS), scrapie, in transgenic murine models and in culture, where microglial activation often accompanies prion protein deposition and neuronal loss. This article will review the roles of microglia in spongiform encephalopathies.}, Author = {Rezaie, P. and Lantos, P. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0165-0173}, Journal = {Brain Res Brain Res Rev}, Keywords = {Research Support, Non-U.S. Gov't;Encephalitis;11 Glia;Microglia;review, tutorial;Animals;Humans;review;Prion Diseases}, Medline = {21142106}, Month = {3}, Nlm_Id = {8908638}, Number = {1}, Organization = {Department of Neuropathology, Institute of Psychiatry, King's College London, DeCrespigny Park, SE5 8AF, London, UK. p.rezaie\@iop.kcl..ac.uk}, Pages = {55-72}, Pii = {S016501730100042X}, Pubmed = {11245886}, Title = {Microglia and the pathogenesis of spongiform encephalopathies}, Uuid = {CCA46AF7-BFE3-445B-BB1F-ACA4D5976F29}, Volume = {35}, Year = {2001}} @article{Rezaie:1997a, Abstract = {Microglia represent the primary immune effector cells of the adult central nervous system (CNS). The origin of these cells has been a subject of intense debate over the last century. However, immunohistochemical and chimera developmental studies in rodents support the hypothesis that microglia are monocytic in origin. There have been relatively few studies to date on microglia in human fetal development, and the mechanisms by which microglial precursors enter the developing CNS are as yet unknown. It is possible that microglial precursors use combinations of adhesion molecules on cerebral endothelium to gain entry into the developing CNS. In the present study, we have shown the distribution of microglia within human fetal cerebral cortex between 16 and 22 weeks of gestation using RCA-1 lectin histochemistry. We have also demonstrated dual anti-macrophage antibody labelling of these cells in conjunction with adhesion molecules ICAM-1, ICAM-2 and PECAM on cerebral endothelium throughout this period. We conclude that fetal microglia usually occur at highly vascularised sites within the developing human fetal brain and are more specifically associated with the expression of ICAM-2 on cerebral endothelium.}, Author = {Rezaie, P. and Cairns, N. J. and Male, D. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Endothelium, Vascular;Gestational Age;Research Support, Non-U.S. Gov't;Embryonic and Fetal Development;Comparative Study;Lectins;Immunohistochemistry;Biological Markers;11 Glia;Microglia;Macrophages;Histocytochemistry;Humans;Brain;Cell Adhesion Molecules, Neuronal}, Medline = {98126196}, Month = {12}, Nlm_Id = {8908639}, Number = {1-2}, Organization = {Department of Neuropathology, Institute of Psychiatry, London, UK. spkadkm\@iop.bpmf.ac.uk}, Pages = {175-89}, Pubmed = {9466720}, Title = {Expression of adhesion molecules on human fetal cerebral vessels: relationship to microglial colonisation during development}, Uuid = {9D160946-E20F-41F3-85A0-ECDC4F5E872F}, Volume = {104}, Year = {1997}} @article{Rezaie:1999, Abstract = {Microglia, the intrinsic macrophages of the nervous system, colonise the cerebrum around the second trimester in man. In order to determine the extent of microglial influx into the nervous system, we have examined their distribution within the human fetal spinal cord in relation to astrocytic and vascular development between 9 and 16 weeks of gestation, using conventional immunohistochemistry [CD11b; CD45; CD64; CD68; ICAM-1; ICAM-2; VCAM-1; PECAM; GFAP; vimentin] and lectin histochemistry [RCA-1]. Microglia are identifiable by 9 weeks, within the ventricular/sub-ventricular zones. Human fetal microglia display heterogeneity in phenotype and are more readily identified by CD68 in the spinal cord. There is a marked influx of cells dorsal and ventral to the neural cavity, from the marginal layer [meninges/connective tissue] with advancing gestational age, with greatest cell densities towards the end of the time period in this study. This inward migration is associated with progressive vascularisation, ICAM-2 expression and co-localises with GFAP and vimentin positive radial glia. The patterns of microglial migration in human fetal cord differ from that within the cerebrum, but generally conform to a route following white to gray matter.}, Author = {Rezaie, P. and Patel, K. and Male, D. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Gestational Age;Research Support, Non-U.S. Gov't;Fetus;Immunohistochemistry;Phenotype;11 Glia;Microglia;Spinal Cord;Humans}, Medline = {99296479}, Month = {6}, Nlm_Id = {8908639}, Number = {1}, Organization = {Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London SE5 8JN, UK. p.rezaie\@iop.kcl.ac.uk}, Pages = {71-81}, Pii = {S0165380699000437}, Pubmed = {10366704}, Title = {Microglia in the human fetal spinal cord--patterns of distribution, morphology and phenotype}, Uuid = {1509467B-ADDB-416C-9512-C8040B46C062}, Volume = {115}, Year = {1999}} @article{Rezaie:2004, Abstract = {We have recently begun to gain a clearer understanding of the phasing and patterns of colonization of the developing human brain by microglia. In this study we investigated the distribution, morphology and phenotype of microglia specifically within the wall of the human telencephalon from 12 to 24 gestational weeks (gw), a period that corresponds to the development of thalamocortical fibres passing through the transient subplate region of the developing cerebral wall. Sections from a total of 45 human fetal brains were immunoreacted to detect CD68 and MHC class II antigens and histochemically reacted with RCA-1 and tomato lectins. These markers were differentially expressed by anatomically discrete populations of microglia in the cerebral wall: two cell populations were noted during the initial phase of colonization (12-14 gw): (i) CD68++ RCA-1+ MHC II- amoeboid cells aligned within the subplate, and (ii) RCA-1++ CD68- MHC II- progenitors in the marginal layer and lower cortical plate that progressively ramified within the subplate, without seemingly passing through an 'amoeboid' state. At this stage microglia were largely absent from the germinal layers and the intermediate zone. From 14 to 15 gw, however, MHC class II positive cells were also detected within germinal layers and in the corpus callosum, and these cells, which coexpressed CD68 antigen (a marker associated with phagocytosis), further populated the lower half of the telencephalon from 18 to 24 gw. These findings are discussed in relation to developmental events that take place during the second trimester within the wall of the telencephalon.}, Author = {Rezaie, and Dean, and Male, and Ulfig,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {11 Glia}, Nlm_Id = {9110718}, Organization = {Department of Biological Sciences, Faculty of Science, The Open University, Walton Hall, Milton Keynes, MK7 6AA, UK; Department of Neuropathology, Institute of Psychiatry, King's College London, DeCrespigny Park, London SE5 8AF, UK.}, Pii = {bhh194}, Pubmed = {15483047}, Title = {Microglia in the Cerebral Wall of the Human Telencephalon at Second Trimester}, Uuid = {E4FA846C-D0FE-4933-966D-F24F3BBC692D}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh194}} @article{Rezaie:2002, Abstract = {Microglia are mononuclear phagocytes of the central nervous system and are considered to derive from circulating bone marrow progenitors that colonize the developing human nervous system in the second trimester. They first appear as ameboid forms and progressively differentiate to process-bearing "ramified" forms with maturation. Signals driving this transformation are known to be partly derived from astrocytes. In this investigation we have used cocultures of astrocytes and microglia to demonstrate the relationship between motility and morphology of microglia associated with signals derived from astrocytes. Analysis of progressive cultures using time-lapse video microscopy clearly demonstrates the dynamic nature of microglia. We observe that ameboid microglial cells progressively ramify when cocultured with astrocytes, mirroring the "differentiation" of microglia in situ during development. We further demonstrate that individual cells undergo morphological transformations from "ramified" to "bipolar" to "tripolar" and "ameboid" states in accordance with local environmental cues associated with astrocytes in subconfluent cultures. Remarkably, cells are still capable of migration at velocities of 20-35 microm/h in a fully ramified state overlying confluent astrocytes, as determined by image analysis of motility. This is in keeping with the capacity of microglia for a rapid response to inflammatory cues in the CNS. We also demonstrate selective expression of the chemokines MIP-1alpha and MCP-1 by confluent human fetal astrocytes in cocultures and propose a role for these chemotactic cytokines as regulators of microglial motility and differentiation. The interchangeable morphological continuum of microglia supports the view that these cells represent a single heterogeneous population of resident mononuclear phagocytes capable of marked plasticity.}, Author = {Rezaie, P. and Trillo-Pazos, G. and Greenwood, J. and Everall, I. P. and Male, D. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0014-4827}, Journal = {Exp Cell Res}, Keywords = {Cell Differentiation;Research Support, Non-U.S. Gov't;Image Processing, Computer-Assisted;Fetus;Cell Communication;Macrophage Inflammatory Protein-1;Astrocytes;Stem Cells;Coculture Techniques;Microscopy, Video;11 Glia;Microglia;Chemokines;Humans;Monocyte Chemoattractant Protein-1;Cell Movement;Brain}, Medline = {21846026}, Month = {3}, Nlm_Id = {0373226}, Number = {1}, Organization = {Department of Neuropathology, Institute of Psychiatry, King's College London, DeCrespigny Park, London, SE5 8AF, United Kingdom. p.rezaie\@iop.kcl.ac.uk}, Pages = {68-82}, Pii = {S001448270195431X}, Pubmed = {11855858}, Title = {Motility and ramification of human fetal microglia in culture: an investigation using time-lapse video microscopy and image analysis}, Uuid = {A15F1383-C756-42F8-8289-1E95910FC703}, Volume = {274}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/excr.2001.5431}} @article{Rezaie:2002a, Abstract = {Chemokines play specific roles in directing the recruitment of leukocyte subsets into inflammatory foci within the central nervous system (CNS). The involvement of these cytokines as mediators of inflammation is widely accepted. Recently, it has become evident that cells of the CNS (astrocytes, microglia, and neurons) not only synthesize, but also respond functionally or chemotactically to chemokines. We previously reported developmental events associated with colonization of the human fetal CNS by mononuclear phagocytes (microglial precursors), which essentially takes place within the first two trimesters of life. As part of the array of signals driving colonization, we noted specific anatomical distribution of chemokines and chemokine receptors expressed during this period. In order to further characterize expression of these molecules, we have isolated and cultured material from human fetal CNS. We demonstrate that unstimulated subconfluent human fetal glial cultures express high levels of CCR2 and CXCR4 receptors in cytoplasmic vesicles. Type I astrocytes, and associated ameboid microglia in particular, express high levels of surface and cytoplasmic CXCR4. Of the chemokines tested (MIP-1alpha, MIP-1beta, MCP-1, MCP-3, RANTES, SDF-1, IL-8, IP-10), only MIP-1alpha, detected specifically on microglia, was expressed both constitutively and consistently. Low variable levels of MCP-1, MIP-1alpha, and RANTES were also noted in unstimulated glial cultures. Recombinant human chemokines rhMCP-1 and rhMIP-1alpha also displayed proliferative effects on glial cultures at [10 ng/ml], but displayed variable effects on CCR2 levels on these cells. rhMCP-1 specifically upregulated CCR2 expression on cultured glia at [50 ng/ml]. It is gradually becoming evident that chemokines are important in embryonic development. The observation that human fetal glial cells and their progenitors express specific receptors for chemokines and can be stimulated to produce MCP-1, as well as proliferate in response to chemokines, supports a role for these cytokines as regulatory factors during development.}, Author = {Rezaie, P. and Trillo-Pazos, G. and Everall, I. P. and Male, D. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Fetus;Receptors, CXCR4;Astrocytes;Cells, Cultured;Humans;Recombinant Proteins;Microglia;Lipopolysaccharides;Cell Movement;11 Glia;Chemokines, CC;Receptors, Chemokine;Macrophage Inflammatory Protein-1;Cell Division;Central Nervous System;Monocyte Chemoattractant Protein-1;Immunohistochemistry;Colony-Stimulating Factors;Research Support, Non-U.S. Gov't}, Medline = {21610744}, Month = {1}, Nlm_Id = {8806785}, Number = {1}, Organization = {Department of Neuropathology, Institute of Psychiatry, King's College London, London, UK. p.rezaie\@iop.kcl.ac.uk}, Pages = {64-75}, Pii = {10.1002/glia.1128}, Pubmed = {11746784}, Title = {Expression of beta-chemokines and chemokine receptors in human fetal astrocyte and microglial co-cultures: potential role of chemokines in the developing CNS}, Uuid = {7AD40F64-0799-4088-B9B7-DC9284F03023}, Volume = {37}, Year = {2002}} @article{Rezaie:2002b, Abstract = {More than a century and a half has elapsed since the first accounts of mesodermal phagocytic elements were proposed within the central nervous system. Over the intervening decades, body and substance were added to this concept through the advancement of histological techniques at the disposal of the researcher and the acute and keen-minded skills of the pathologist. Notable among these pioneering efforts were the contributions of W. Ford Robertson, Santiago Ramon y Cajal, Pio del Rio-Hortega and Wilder Penfield amongst an entire cavalcade of other noteworthy figures. The term 'mesoglia' and 'third element of the nervous system' was bestowed upon these cells towards the beginning of the twentieth century to account for their separate origins from neurons and macroglia. It was later amended by del Rio-Hortega in 1919, to 'microglia' in order to further discriminate between true mesodermal elements and oligodendrocytes, previously regarded as a component of 'mesoglia'. This particular contention sparked much controversy among del Rio-Hortega's peers and resulted in an escalation of fruitful research throughout Europe that eventually declined up to the outbreak of the Second World War. The post-war years were a period of the 'dark ages' that cast doubt on the very existence and nature of microglia, until the 'renaissance' of research was once again rejuvenated in the 1960s, by a new cohort of intrigued minds: Cammermeyer, Blinzinger, Kreutzberg and others who saw in the 'third element' the potential that is now commonly ascribed to microglia: the intrinsic immune effector cells of the CNS. It is now universally accepted that microglia are involved as the first line of rapid defence in any pathology of the nervous system, and as such, present a diagnostic tool for the neuropathologist. Although our knowledge of microglia stems from an extensive body of work conducted over the last two decades, much of the earlier work (pre-1960s) has remained somewhat obscure. This is partly accountable due to the limited availability of translated works, and additionally to the lack of a compendium of these articles. This paper will present a comprehensive overview of the pioneering research on mononuclear phagocytes within the central nervous system, which has direct bearing on our present-day understanding of the concept of microglia.}, Author = {Rezaie, Payam and Male, David}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0964-704X}, Journal = {J Hist Neurosci}, Keywords = {History, 19th Century;Monocytes;Ectoderm;Neuroglia;Central Nervous System;History, 20th Century;Neurosciences;historical article;11 Glia;Microglia;Mesoderm;Animals;Humans;Phagocytosis}, Medline = {22445846}, Month = {12}, Nlm_Id = {9441330}, Number = {4}, Organization = {Department of Neuropathology, Institute of Psychiatry, SE5 8AF, UK. p.rezaie\@iop.kc1.ac.uk}, Pages = {325-74}, Pubmed = {12557654}, Title = {Mesoglia µglia--a historical review of the concept of mononuclear phagocytes within the central nervous system}, Uuid = {01EA53A6-3A0D-437E-A69F-A3FBB626BCEB}, Volume = {11}, Year = {2002}} @article{Rezaie:1999a, Abstract = {Microglia are the immune effector cells of the nervous system. The prevailing view is that microglia are derived from circulating precursors in the blood, which originate from the bone-marrow. Colonisation of the central nervous system (CNS) by microglia is an orchestrated response during human fetal development related to the maturation of the nervous system. It coincides with vascularisation, formation of radial glia, neuronal migration and myelination primarily in the 4th-5th months and beyond. Microglial influx generally conforms to a route following white matter tracts to gray areas. We have observed that colonisation of the spinal cord begins around 9 weeks, with the major influx and distribution of microglia commencing around 16 weeks. In the cerebrum, colonisation is in progress during the second trimester, and ramified microglial forms are widely distributed within the intermediate zone by the first half of intra-uterine life (20-22 weeks). A distinct pattern of migration occurs along radial glia, white matter tracts and vasculature. The distribution of these cells is likely to be co-ordinated by spatially and temporally regulated, anatomical expression of chemokines including RANTES and MCP-1 in the cortex; by ICAM-2 and PECAM on radiating cerebral vessels and on capillaries within the germinal layer, and apoptotic cell death overlying this region. The phenotype and functional characteristics of fetal microglia are also outlined in this review. The need for specific cellular interactions and targeting is greater within the central nervous system than in other tissues. In this respect, microglia may additionally contribute towards CNS histogenesis.}, Author = {Rezaie, P. and Male, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1059-910X}, Journal = {Microsc Res Tech}, Keywords = {Research Support, Non-U.S. Gov't;Embryonic and Fetal Development;Cytokines;Phenotype;Colony-Forming Units Assay;Microglia;Spinal Cord;11 Glia;Humans;Brain;Cell Movement;review}, Medline = {99330517}, Month = {6}, Nlm_Id = {9203012}, Number = {6}, Organization = {Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, United Kingdom. p.rezaie\@iop.kcl.ac.uk}, Pages = {359-82}, Pii = {10.1002/(SICI)1097-0029(19990615)45:6<359::AID-JEMT4>3.0.CO;2-D}, Pubmed = {10402264}, Title = {Colonisation of the developing human brain and spinal cord by microglia: a review}, Uuid = {3695183E-35AB-4F0D-9A94-BDEF23E65DA5}, Volume = {45}, Year = {1999}} @article{Rezaie:2002c, Abstract = {Periventricular leukomalacia (PVL) occurring in premature infants, represents a major precursor for neurological and intellectual impairment, and cerebral palsy in later life. The disorder is characterized by multifocal areas of necrosis found deep in the cortical white matter, which are often symmetrical and occur adjacent to the lateral ventricles. There is no known cure for PVL. Factors predisposing to PVL include birth trauma, asphyxia and respiratory failure, cardiopulmonary defects, premature birth/low birthweight, associated immature cerebrovascular development and lack of appropriate autoregulation of cerebral blood flow in response to hypoxic-ischemic insults. The intrinsic vulnerability of oligodendrocyte precursors is considered as central to the pathogenesis of PVL. These cells are susceptible to a variety of injurious stimuli including free radicals and excitotoxicity induced by hypoxic-ischemic injury (resulting from cerebral hypoperfusion), lack of trophic stimuli, as well as secondary associated events involving microglial and astrocytic activation and the release of pro-inflammatory cytokines TNF-alpha and IL-6. It is yet unclear whether activated astrocytes and microglia act as principal participants in the development of PVL lesions, or whether they are representatives of an incidental pathological response directed towards repair of tissue injury in PVL. Nevertheless, the accumulated evidence points to a pathological contribution of microglia towards damage. The topography of lesions in PVL most likely reflects a combination of the relatively immature cerebrovasculature together with a failure in perfusion and/or hypoxia during the greatest period of vulnerability occurring around mid-to-late gestation. Mechanisms underlying the pathogenesis of PVL have so far been related to prenatal ischemic injury to the brain initiated within the third trimester, which result in global cognitive and developmental delay and motor disturbances. Over the past few years, several epidemiological and experimental studies have implicated intrauterine infection and chorioamnionitis as causative in the pathogenesis of PVL. In particular, recent investigations have shown that inflammatory responses in the fetus and neonate can contribute towards neonatal brain injury and development-related disabilities including cerebral palsy. This review presents current concepts on the pathogenesis of PVL and emphasizes the increasing evidence for an inflammatory pathogenic component to this disorder, either resulting from hypoxic-ischemic injury or from infection. These findings provide the basis for clinical approaches targeted at protecting the premature brain from inflammatory damage, which may prove beneficial for treating PVL, if identified early in pathogenesis.}, Author = {Rezaie, Payam and Dean, Andrew}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0919-6544}, Journal = {Neuropathology}, Keywords = {Leukomalacia, Periventricular;11 Glia;review, tutorial;Humans;Brain;Infant, Newborn;review}, Medline = {22303200}, Month = {9}, Nlm_Id = {9606526}, Number = {3}, Organization = {Department of Neuropathology, Institute of Psychiatry, King's College London, UK. p.rezaie\@iop.kcl.ac.uk}, Pages = {106-32}, Pubmed = {12416551}, Title = {Periventricular leukomalacia, inflammation and white matter lesions within the developing nervous system}, Uuid = {07489C42-5780-4070-8BF0-3CF4893825E5}, Volume = {22}, Year = {2002}} @article{Rheims:2008, Abstract = {The neonatal period is critical for seizure susceptibility, and neocortical networks are central in infantile epilepsies. We report that application of 4-aminopyridine (4-AP) to immature (P6-P9) neocortical slices generates layer-specific interictal seizures (IISs) that transform after recurrent seizures to ictal seizures (ISs). During IISs, cell-attached recordings show action potentials in interneurons and pyramidal cells in L5/6 and interneurons but not pyramidal neurons in L2/3. However, L2/3 pyramidal neurons also fire during ISs. Using single N-methyl-d-aspartate (NMDA) channel recordings for measuring the cell resting potential (Em), we show that transition from IISs to ISs is associated with a gradual Em depolarization of L2/3 and L5/6 pyramidal neurons that enhances their excitability. Bumetanide, a NKCC1 co-transporter antagonist, inhibits generation of IISs and prevents their transformation to ISs, indicating the role excitatory GABA in epilepsies. Therefore deep layer neurons are more susceptible to seizures than superficial ones. The initiating phase of seizures is characterized by IISs generated in L5/6 and supported by activation of both L5/6 interneurons and pyramidal cells. IISs propagate to L2/3 via activation of L2/3 interneurons but not pyramidal cells, which are mostly quiescent at this phase. In superficial layers, a persistent increase in excitability of pyramidal neurons caused by Em depolarization is associated with a transition from largely confined GABAergic IIS to ictal events that entrain the entire neocortex.}, Author = {Rheims, Sylvain and Represa, Alfonso and Ben-Ari, Yehezkel and Zilberter, Yuri}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0375404}, Number = {2}, Organization = {Institut de Neurobiologie de la Mediterranee, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale U901, Universit{\'e} de la M{\'e}diterran{\'e}e, Marseille, France. sylvain.rheims\@free.fr}, Pages = {620-8}, Pii = {90403.2008}, Pubmed = {18497363}, Title = {Layer-specific generation and propagation of seizures in slices of developing neocortex: role of excitatory GABAergic synapses}, Uuid = {5BF96171-A918-4FB2-88BF-6CE27F12A519}, Volume = {100}, Year = {2008}, url = {papers/Rheims_JNeurophysiol2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.90403.2008}} @article{Ribar:2000, Abstract = {The Ca(2+)/calmodulin-dependent protein kinase CaMKIV was first identified in the cerebellum and has been implicated in nuclear signaling events that control neuronal growth, differentiation, and plasticity. To understand the physiological importance of CaMKIV, we disrupted the mouse Camk4 gene. The CaMKIV null mice displayed locomotor defects consistent with altered cerebellar function. Although the overall cytoarchitecture of the cerebellum appeared normal in the Camk4(-/-) mice, we observed a significant reduction in the number of mature Purkinje neurons and reduced expression of the protein marker calbindin D28k within individual Purkinje neurons. Western immunoblot analyses of cerebellar extracts also established significant deficits in the phosphorylation of cAMP response element-binding protein at serine-133, a proposed target of CaMKIV. Additionally, the absence of CaMKIV markedly altered neurotransmission at excitatory synapses in Purkinje cells. Multiple innervation by climbing fibers and enhanced parallel fiber synaptic currents suggested an immature development of Purkinje cells in the Camk4(-/-) mice. Together, these findings demonstrate that CaMKIV plays key roles in the function and development of the cerebellum.}, Author = {Ribar, T. J. and Rodriguiz, R. M. and Khiroug, L. and Wetsel, W. C. and Augustine, G. J. and Means, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {in vitro;Heterozygote;Electric Stimulation;Purkinje Cells;Animals;Phosphorylation;Cerebellar Diseases;Protein-Serine-Threonine Kinases;Ca(2+)-Calmodulin Dependent Protein Kinase;research support, non-u.s. gov't;Behavior, Animal;Cyclic AMP Response Element-Binding Protein;Mice, Knockout;Homozygote;research support, u.s. gov't, p.h.s.;Blotting, Western;Cyclic AMP-Dependent Protein Kinases;Cerebellum;Mice;24 Pubmed search results 2008;Excitatory Postsynaptic Potentials}, Month = {11}, Nlm_Id = {8102140}, Number = {22}, Organization = {Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.}, Pages = {RC107}, Pii = {20004718}, Pubmed = {11069976}, Title = {Cerebellar defects in Ca2+/calmodulin kinase IV-deficient mice}, Uuid = {AD02D45B-AA1C-4D98-9820-B8A7E496ED02}, Volume = {20}, Year = {2000}} @article{Ricard:2001, Abstract = {The Unc-33-like phosphoprotein/collapsin response mediator protein (Ulip/CRMP) family consists of four homologous phosphoproteins considered crucial for brain development. Autoantibodies produced against member(s) of this family by patients with paraneoplastic neurological diseases have made it possible to clone a fifth human Ulip/CRMP and characterize its cellular and anatomical distribution in developing brain. This protein, referred to as Ulip6/CRMP5, is highly expressed during rat brain development in postmitotic neural precursors and in the fasciculi of fibers, suggesting its involvement in neuronal migration/differentiation and axonal growth. In the adult, Ulip6/CRMP5 is still expressed in some neurons, namely in areas that retain neurogenesis and in oligodendrocytes in the midbrain, hindbrain, and spinal cord. Ulip2/CRMP2 and Ulip6/CRMP5 are coexpressed in postmitotic neural precursors at certain times during development and in oligodendrocytes in the adult. Because Ulip2/CRMP2 has been reported to mediate semaphorin-3A (Sema3A) signal in developing neurons, in studies to understand the function of Ulip6/CRMP5 and Ulip2/CRMP2 in the adult, purified adult rat brain oligodendrocytes were cultured in a Sema3A- conditioned medium. Oligodendrocytes were found to have Sema3A binding sites and to express neuropilin-1, the major Sema3A receptor component. In the presence of Sema3A, these oligodendrocytes displayed a dramatic reduction in process extension, which was reversed by removal of Sema3A and prevented by anti-neuropilin-1, anti-Ulip6/CRMP5, anti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand. These results indicate the existence in the adult brain of a Sema3A signaling pathway that modulates oligodendrocyte process extension mediated by neuropilin- 1, Ulip6/CRMP5, and Ulip2/CRMP2, and they open new fields of investigation of neuron/oligodendrocyte interactions in the normal and pathological brain.}, Author = {Ricard, D. and Rogemond, V. and Charrier, E. and Aguera, M. and Bagnard, D. and Belin, M. F. and Thomasset, N. and Honnorat, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {18}, Organization = {Institut National de la Sante et de la Recherche Medicale U 433, Institut Federatif des Neurosciences de Lyon, Hopital Neurologique, 69003 Lyon, France.}, Pages = {7203-14.}, Title = {Isolation and expression pattern of human unc-33-like phosphoprotein 6/collapsin response mediator protein 5 (ulip6/crmp5): coexistence with ulip2/crmp2 in sema3a- sensitive oligodendrocytes}, Uuid = {B7DE1AE7-BF49-4784-93D6-2E67481900AC}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11549731%20http://www.jneurosci.org/cgi/content/full/21/18/7203%20http://www.jneurosci.org/cgi/content/abstract/21/18/7203}} @article{Ricci:1992, Abstract = {Band heterotopia, or "double cortex," is a neuronal migration disorder that consists of a symmetrical subcortical neuronal band. The overlying cortex may be normal or macrogyric. We describe two severely mentally retarded girls, aged 14 and 18 years, who had band heterotopia and Lennox-Gastaut syndrome. Band heterotopia was evident in both hemispheres as a subcortical symmetrical layer isointense with gray matter on magnetic resonance T1- and T2-weighted images. Both patients had atonic seizures, atypical absences, and tonic seizures. The electroencephalograms in both cases showed frequent generalized paroxysms and slow background activity. The association of a Lennox-Gastaut syndrome with double cortex in these two patients and in a previously reported autopsy-confirmed case suggests that this malformation may be responsible for other similar cases.}, Author = {Ricci, S. and Cusmai, R. and Fariello, G. and Fusco, L. and Vigevano, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0003-9942}, Journal = {Arch Neurol}, Keywords = {Epilepsy;Hemiplegia;Electroencephalography;10 Development;Magnetic Resonance Imaging;Adolescent;Syndrome;Female;24 Pubmed search results 2008;Seizures;10 genetics malformation;Humans;Cerebral Cortex;Neurons;case reports}, Month = {1}, Nlm_Id = {0372436}, Number = {1}, Organization = {Section of Neurophysiology, Bambino Ges\`{u} Children's Hospital, Rome, Italy.}, Pages = {61-4}, Pubmed = {1728265}, Title = {Double cortex. A neuronal migration anomaly as a possible cause of Lennox-Gastaut syndrome}, Uuid = {625B5C12-1F00-406A-9B6B-B7B72062C728}, Volume = {49}, Year = {1992}} @article{Rickmann:1987, Abstract = {The temporal and spatial patterns of development of radial glial processes in the rat dentate gyrus have been studied in immunohistochemical preparations stained for the presence of either the glial fibrillary acidic protein (GFAP) or the vimentin-associated antigen R4. Additional electron microscopic (EM) observations were made from material prepared either immunohistochemically or by the Golgi method. R4 immunoreactive radial fibers were observed in the incipient dentate gyrus as early as E13 and by E14 the density of stained fibers was clearly higher in the anlage of the dentate gyrus than in the adjacent hippocampus. By E15 it was possible to identify in the EM the endfeet of radial glial cells that contained numerous glycogen particles. GFAP-positive radial processes were first observed on E17; these processes tended to be of larger diameter than those stained with the R4 antibody, suggesting that they were among the more mature processes. The orientation of both the R4- and GFAP-positive glial processes changed throughout the last week of embryonic life and by the end of the first postnatal week they formed a complex meshwork of intertwined processes. The distribution of their cell bodies also changed with time; initially their perikarya were located in the neuroepithelium at the lateral margin of the hippocampal primordium; later they were found mainly beneath the granule cell layer. Dividing cells that contained GFAP were observed along the trajectory of the migrating granule cell precursors and in the hilus of the dentate gyrus; at later stages some GFAP-positive mitotic figures were seen within and immediately below the granule cell layer. On the basis of these observations, we have attempted to reconstruct the role that radial glial processes play in the morphogenesis of the dentate gyrus. First, radial processes extend from the neuroepithelium to the pial surface prior to the migration of neurons that will form the dentate gyrus. These early generated glia appear to form the boundaries of the developing dentate gyrus and provide an internal lattice that may guide the initial wave of migrating progenitor cells. As the dentate gyrus enlarges, these early formed processes maintain their contacts along the hippocampal fissure and along the pial surface of the dentate anlage. Thus, with time they become increasingly distorted and are ultimately compressed into two bundles; one lies deep to the hippocampal fissure parallel to the granule cell layer and the other is located at the fimbriodentate juncture.(ABSTRACT TRUNCATED AT 400 WORDS)}, Author = {Rickmann, M. and Amaral, D. G. and Cowan, W. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Embryo;Neuroglia;Research Support, Non-U.S. Gov't;Hippocampus;Rats;Research Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Cell Division;Animals, Newborn;Animals;Rats, Inbred Strains}, Medline = {88059849}, Month = {10}, Nlm_Id = {0406041}, Number = {4}, Organization = {Developmental Neurobiology Laboratory, Salk Institute for Biological Studies, San Diego, California 92138.}, Pages = {449-79}, Pubmed = {3680638}, Title = {Organization of radial glial cells during the development of the rat dentate gyrus}, Uuid = {2C5E7838-690C-11DA-A4B6-000D9346EC2A}, Volume = {264}, Year = {1987}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.902640403}} @article{Riederer:1990, Abstract = {MAP5, a microtubule-associated protein characteristic of differentiating neurons, was studied in the developing visual cortex and corpus callosum of the cat. In juvenile cortical tissue, during the first month after birth, MAP5 is present as a protein doublet of molecular weights of 320 and 300 kDa, defined as MAP5a and MAP5b, respectively. MAP5a is the phosphorylated form. MAP5a decreases two weeks after birth and is no longer detectable at the beginning of the second postnatal month; MAP5b also decreases after the second postnatal week but more slowly and it is still present in the adult. In the corpus callosum only MAP5a is present between birth and the end of the first postnatal month. Afterwards only MAP5b is present but decreases in concentration more than 3-fold towards adulthood. Our immunocytochemical studies show MAP5 in somata, dendrites and axonal processes of cortical neurons. In adult tissue it is very prominent in pyramidal cells of layer V. In the corpus callosum MAP5 is present in axons at all ages. There is strong evidence that MAP5a is located in axons while MAP5b seems restricted to somata and dendrites until P28, but is found in callosal axons from P39 onwards. Biochemical experiments indicate that the state of phosphorylation of MAP5 influences its association with structural components. After high speed centrifugation of early postnatal brain tissue, MAP5a remains with pellet fractions while most MAP5b is soluble. In conclusion, phosphorylation of MAP5 may regulate (1) its intracellular distribution within axons and dendrites, and (2) its ability to interact with other subcellular components.}, Author = {Riederer, B. M. and Guadano-Ferraz, A. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Aging;Cerebral Cortex;Phosphorylation;Organ Specificity;Cats;Immunohistochemistry;Not relevant;11 Glia;Subcellular Fractions;Animals, Newborn;Support, Non-U.S. Gov't;Microtubule-Associated Proteins;Molecular Weight;Animals;Corpus Callosum}, Medline = {91084995}, Month = {11}, Nlm_Id = {8908639}, Number = {2}, Organization = {Institute of Anatomy, University of Lausanne, Switzerland.}, Pages = {235-43}, Pubmed = {2261685}, Title = {Difference in distribution of microtubule-associated proteins 5a and 5b during the development of cerebral cortex and corpus callosum in cats: dependence on phosphorylation}, Uuid = {FFEAD651-B423-4663-B573-8136D9BBED37}, Volume = {56}, Year = {1990}} @article{Riederer:1991, Abstract = {During the postnatal development of cat visual cortex and corpus callosum the molecular composition of tau proteins varied with age. In both structures, they changed between postnatal days 19 and 39 from a set of two juvenile forms to a set of at least two adult variants with higher molecular weights. During the first postnatal week, tau proteins were detectable with TAU-1 antibody in axons of corpus callosum and visual cortex, and in some perikarya and dendrites in the visual cortex. At later ages, tau proteins were located exclusively within axons in all cortical layers and in the corpus callosum. Dephosphorylation of postnatal day 11 cortical tissue by alkaline phosphatase strongly increased tau protein immunoreactivity on Western blots and in numerous perikarya and dendrites in all cortical layers, in sections, suggesting that some tau forms had been unmasked. During postnatal development the intensity of this phosphate-dependent somatodendritic staining decreased, but remained in a few neurons in cortical layers II and III. On blots, the immunoreactivity of adult tau to TAU-1 was only marginally increased by dephosphorylation. Other tau antibodies (TAU-2, B19 and BR133) recognized two juvenile and two adult cat tau proteins on blots, and localized tau in axons or perikarya and dendrites in tissue untreated with alkaline phosphatase. Tau proteins in mature tissue were soluble and not associated with detergent-resistant structures. Furthermore, dephosphorylation by alkaline phosphatase resulted in the appearance of more tau proteins in soluble fractions. Therefore tau proteins seem to alter their degree of phosphorylation during development. This could affect microtubule stability as well as influence axonal and dendritic differentiation.}, Author = {Riederer, and Innocenti,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Not relevant;11 Glia}, Month = {10}, Nlm_Id = {8918110}, Number = {11}, Organization = {Institut d'Anatomie, Universit{\'e} de Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.}, Pages = {1134-1145}, Pii = {ejn_03111134}, Pubmed = {12106243}, Title = {Differential Distribution of Tau Proteins in Developing Cat Cerebral Cortex and Corpus Callosum}, Uuid = {277CAA21-ABD5-402D-BA4C-EA6FC171FA2A}, Volume = {3}, Year = {1991}} @article{Riederer:1992, Abstract = {The microtubule-associated protein MAP2 was studied in the developing cat visual cortex and corpus callosum. Biochemically, no MAP2a was detectable in either structure during the first postnatal month; adult cortex revealed small amounts of MAP2a. MAP2b was abundant in cortical tissue during the first postnatal month and decreased in concentration towards adulthood; it was barely detectable in corpus callosum at all ages. MAP2c was present in cortex and corpus callosum at birth; in cortex it consisted of three proteins of similar molecular weights between 65 and 70 kD. The two larger, phosphorylated forms disappeared after postnatal day 28, the smaller form after day 39. In corpus callosum, MAP2c changed from a phosphorylated to an unphosphorylated variant during the first postnatal month and then disappeared. Immunocytochemical experiments revealed MAP2 in cell bodies and dendrites of neurons in all cortical layers, from birth onwards. In corpus callosum, in the first month after birth, a little MAP2, possibly MAP2c, was detectable in axons. The present data indicate that MAP2 isoforms differ in their cellular distribution, temporal appearance and structural association, and that their composition undergoes profound changes during the period of axonal stabilization and dendritic maturation.}, Author = {Riederer, and Innocenti,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Not relevant;11 Glia}, Nlm_Id = {8918110}, Number = {12}, Organization = {Institut d'Anatomie, Universit{\'e} de Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland.}, Pages = {1376-1386}, Pii = {ejn_04121376}, Pubmed = {12106401}, Title = {MAP2 Isoforms in Developing Cat Cerebral Cortex and Corpus Callosum}, Uuid = {C521CCE9-2C75-4639-B338-BD1ECFE6D8C9}, Volume = {4}, Year = {1992}} @article{Riederer:2004, Abstract = {The corpus callosum (CC) is a major telencephalic commissure containing mainly cortico-cortical axons and glial cells. We have identified neurons in the CC of the cat and quantified their number at different postnatal ages. An antibody against microtubule-associated protein 2 was used as a marker of neurons. Immunocytochemical double-labelling with neuron-specific enolase or gamma-aminobutyric acid antibodies in the absence of glial fibrillary acidic protein positivity confirmed the neuronal phenotype of these cells. CC neurons were also stained with anti-calbindin and anti-calretinin antibodies, typical for interneurons, and with an anti-neurofilament antibody, which in neocortex detects pyramidal neurons. Together, these findings suggest that the CC contains a mixed population of neuronal types. The quantification was corrected for double counting of adjacent sections and volume changes during CC development. Our data show that CC neurons are numerous early postnatally, and their number decreases with age. At birth, about 570 neurons are found within the CC boundaries and their number drops to about 200 in the adult. The distribution of the neurons within the CC also changes in development. Initially, many neurons are found throughout the CC, while at later ages they become restricted to the boundaries of the CC, and in the adult to the rostrum of the CC close to the septum pellucidum or to the indusium griseum. Although origin and function of transient CC neurons in development and in adulthood remain unknown, they are likely to be interstitial neurons. Some of them have well-developed and differentiated processes and resemble pyramidal cells or interneurons. An axon-guiding function during the early postnatal period can not be excluded.}, Author = {Riederer, Beat M. and Berbel, Pere and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Glial Fibrillary Acidic Protein;Cats;Comparative Study;Not relevant;11 Glia;Animals, Newborn;Animals;Support, Non-U.S. Gov't;Microtubule-Associated Proteins;Neurons;Corpus Callosum}, Month = {4}, Nlm_Id = {8918110}, Number = {8}, Organization = {Institut de Biologie Cellulaire et de Morphologie, Universit{\'e} de Lausanne, Rue du Bugnon 9, 1005 Lausanne, Switzerland. BeatMichel.Reiderer\@ibcm.unil.ch}, Pages = {2039-46}, Pii = {EJN3305}, Pubmed = {15090031}, Title = {Neurons in the corpus callosum of the cat during postnatal development}, Uuid = {820890E3-5324-4A8B-9AE4-CA323666836D}, Volume = {19}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2004.03305.x}} @article{Rieske:1989, Abstract = {In order to study microglial cells and microglia-derived brain macrophages in vitro, a method has been developed which allows the transfer of mitotic microglial cells from adult rat brain into tissue culture. The studies were performed on facial motor nuclei which were explanted after axotomy of the facial nerve. Outgrowing cells were identified and characterized by (i) morphological criteria using light and electron microscopy, (ii) in vivo [3H]thymidine labeling combined with subsequent in vitro autoradiography, (iii) immunocytochemistry for vimentin, GFAP, Fc and complement receptors, MHC antigens, laminin, fibronectin, factor VIII related- and 04 antigen as well as lectin histochemistry, and (iv) functional in vitro tests. In addition, a microglial cell line was established from proliferating cells. The results indicate that perineuronal microglia rather than astrocytes, perivascular cells, oligodendrocytes or endothelial cells may become phagocytic after having been activated by axotomy in situ.}, Author = {Rieske, E. and Graeber, M. B. and Tetzlaff, W. and Czlonkowska, A. and Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Thymidine;Neuroglia;Facial Nerve;Rats;Get paper from library;Time Factors;Not relevant;11 Glia;Cell Division;Macrophages;Male;Animals;Rats, Inbred Strains;Cells, Cultured;Phagocytosis}, Medline = {89323793}, Month = {7}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Department of Neuromorphology, Max-Planck-Institute for Psychiatry, Martinsried, F.R.G.}, Pages = {1-14}, Pubmed = {2752292}, Title = {Microglia and microglia-derived brain macrophages in culture: generation from axotomized rat facial nuclei, identification and characterization in vitro}, Uuid = {12ADF646-750D-4424-8710-603508706DC9}, Volume = {492}, Year = {1989}} @article{Rietze:2000, Abstract = {Previous studies of the adult hippocampus of rodents and primates have reported neuro- and gliogenesis restricted to the region of the dentate gyrus. In the present study, by employing a prolonged bromodeoxyuridine (BrdU) labeling protocol that attempts to account for cytokinetic changes as an animal ages, we have identified mitotically active cells in multiple regions of the hippocampus, especially in Ammon's horn, of the adult mouse. Immediately following the labeling period, the BrdU- labeled cells did not express known markers for neurons and astrocytes. Subsequent analysis at 3-24 weeks after labeling demonstrated BrdU- labeled neurons and glia in these regions of the hippocampus. Although neuro- and gliogenesis in the adult mammalian hippocampus have been reported previously, these results demonstrate that the phenomenon is not limited to the region of the dentate gyrus, but rather extends into Ammon's horn. Furthermore, it suggests that ongoing cell production, albeit discrete and limited in nature, may be widespread in the adult mammalian central nervous system.}, Author = {Rietze, R. and Poulin, P. and Weiss, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {J Comp Neurol}, Keywords = {Hippocampus/cytology/*growth &development/metabolism;BB both;Neurons/cytology/*metabolism;Thymidine;Cell Count;02 Adult neurogenesis migration;Animal;Time Factors;Male;Astrocytes/cytology/*metabolism;03 Adult neurogenesis progenitor source;Stem Cells/cytology/*metabolism;Mice, Inbred Strains;Support, Non-U.S. Gov't;Tritium/diagnostic use;Mitosis/*physiology;Age Factors;Cell Differentiation/physiology;Mice/anatomy &histology/*growth &development/metabolism;Bromodeoxyuridine}, Number = {3}, Organization = {Genes &Development Research Group, Department of Cell Biology and Anatomy, University of Calgary Faculty of Medicine, Calgary, Alberta T2N 4N1, Canada.}, Pages = {397-408.}, Title = {Mitotically active cells that generate neurons and astrocytes are present in multiple regions of the adult mouse hippocampus}, Uuid = {40B78F7E-FF83-46D2-A871-8FDB53BCEFFB}, Volume = {424}, Year = {2000}, url = {papers/Rietze_JCompNeurol2000}} @article{Rietze:2001, Abstract = {The adult mammalian central nervous system (CNS) contains a population of neural stem cells (NSCs) with properties said to include the generation of non-neural progeny. However, the precise identity, location and potential of the NSC in situ remain unclear. We purified NSCs from the adult mouse brain by flow cytometry, and directly examined the cells'properties. Here we show that one type of NSC, which expresses the protein nestin but only low levels of PNA-binding and HSA proteins, is found in both ependymal and subventricular zones and accounts for about 63\%of the total NSC activity. Furthermore, the selective depletion of the population of this stem cell in querkopf mutant mice (which are deficient in production of olfactory neurons) suggests that it acts as a major functional stem cell in vivo. Most freshly isolated NSCs, when co-cultured with a muscle cell line, rapidly differentiated in vitro into myocytes that contain myosin heavy chain (MyHC). This demonstrates that a predominant, functional type of stem cell exists in the periventricular region of the adult brain with the intrinsic ability to generate neural and non-neural cells.}, Author = {Rietze, R. L. and Valcanis, H. and Brooker, G. F. and Thomas, T. and Voss, A. K. and Bartlett, P. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Nature}, Keywords = {02 Adult neurogenesis migration;03 Adult neurogenesis progenitor source;BB}, Number = {6848}, Organization = {The Walter and Eliza Hall Institute of Medical Research, Royal Parade, Parkville, Victoria 3050, Australia.}, Pages = {736-9.}, Title = {Purification of a pluripotent neural stem cell from the adult mouse brain}, Uuid = {38CFF028-17BF-4841-A6E6-CFAE0B1D38A6}, Volume = {412}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11507641}} @article{Rigas:2007, Abstract = {During behavioral quiescence, the neocortex generates spontaneous slow oscillations that consist of Up and Down states. Up states are short epochs of persistent activity that resemble the activated neocortex during arousal and cognition. Although Up states are generated within the cortex, the impact of extrinsic (thalamocortical) and intrinsic (intracortical) inputs on the persistent activity is not known. Using thalamocortical slices, we found that the persistent cortical activity during spontaneous Up states effectively drives thalamocortical relay cells through corticothalamic connections. However, thalamic activity can also precede the onset of cortical Up states, which suggests a role of thalamic activity in triggering cortical Up states through thalamocortical connections. In support of this hypothesis, we found that cutting the connections between thalamus and cortex reduced the incidence of spontaneous Up states in the cortex. Consistent with a facilitating role of thalamic activity on Up states, electrical or chemical stimulation of the thalamus triggered cortical Up states very effectively and enhanced those occurring spontaneously. In contrast, stimulation of the cortex triggered Up states only at very low intensities but otherwise had a suppressive effect on Up states. Moreover, cortical stimulation suppressed the facilitating effect of thalamic stimulation on Up states. In conclusion, thalamocortical inputs facilitate and intracortical inputs suppress cortical Up states. Thus, extrinsic and intrinsic cortical inputs differentially regulate persistent activity, which may serve to adjust the processing state of thalamocortical networks during behavior.}, Author = {Rigas, Pavlos and Castro-Alamancos, Manuel A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {21 Neurophysiology;21 Cortical oscillations;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {16}, Organization = {Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129, USA.}, Pages = {4261-72}, Pii = {27/16/4261}, Pubmed = {17442810}, Title = {Thalamocortical Up states: differential effects of intrinsic and extrinsic cortical inputs on persistent activity}, Uuid = {1E758A38-9DD5-4408-BEEE-E8B5EB953974}, Volume = {27}, Year = {2007}, url = {papers/Rigas_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0003-07.2007}} @article{Rinaman:1991, Abstract = {When the neural tracer Fluoro-Gold is used to retrogradely label a population of axotomized neurons, cellular labeling can persist in the axotomized nucleus even when Nissl staining indicates that the injured neurons have degenerated. In order to determine the identity of the labeled cells that remain, this study combines retrograde transport of Fluoro-Gold with immunocytochemical methods for identification of specific non-neuronal cell types following peripheral axotomy and Fluoro-Gold labeling of motoneurons in the dorsal motor nucleus of the vagus in neonatal and adult rats. Fourteen days following cervical vagotomy in neonatal rats, Nissl staining revealed a virtually complete loss of vagal motoneurons. Fourteen days after cervical vagotomy in adult rats, vagal motoneuronal loss was not yet extensive but chromatolysis had clearly begun. Injection of Fluoro-Gold into the vagus nerve just prior to the vagotomy led to Fluoro-Gold labeling of remaining vagal motoneurons. In addition, many other small, brightly labeled cells were present in the lesioned vagal nuclei of all rats. Immunofluorescent identification of astrocytes with anti-glial fibrillary acidic protein and microglia and macrophages with OX42 (anti-C3bi complement receptor) and ED1 (anti-monocyte/macrophage cytoplasmic antigen) demonstrated that the small, bright Fluoro-Gold-labeled cells were non-neuronal, non-astrocytic phagocytes, including microglia. These results indicate that phagocytic microglia and other macrophages sequester Fluoro-Gold in the axotomized dorsal motor nucleus of the vagus of neonatal and adult rats, leading to persistence of fluorescent cellular labeling following the loss of retrogradely labeled axotomized neurons.}, Author = {Rinaman, L. and Milligan, C. E. and Levitt, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Fluorescent Dyes;Phagocytosis;Nerve Degeneration;Vagotomy;Animals;Macrophages;Rats;Comparative Study;Female;Vagus Nerve;Rats, Inbred Strains;Not relevant;11 Glia;Stilbamidines;Axonal Transport;Animals, Newborn;Neuroglia;Age Factors;Motor Neurons;Support, U.S. Gov't, P.H.S.;Biological Markers}, Medline = {92093168}, Nlm_Id = {7605074}, Number = {3}, Organization = {Medical College of Pennsylvania, Department of Anatomy and Neurobiology, Philadelphia 19129.}, Pages = {765-76}, Pubmed = {1721690}, Title = {Persistence of fluoro-gold following degeneration of labeled motoneurons is due to phagocytosis by microglia and macrophages}, Uuid = {D78E67C7-5B66-424E-B6A7-E26B97F3F70B}, Volume = {44}, Year = {1991}} @article{Ringheim:1995, Abstract = {Interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte macrophage-colony stimulating factor (GM-CSF) are cytokines that bind to receptor complexes comprised of unique alpha-receptor subunits specific for each ligand and a commonly shared beta-receptor subunit. Previous studies have shown that IL-3 and GM-CSF induce mitosis in microglia and macrophage cells, indicating the functional presence of their cognate receptors. In this study, it is shown that the third member of this cytokine group, IL-5, also serves as a microglia mitogen. Proliferative effects were seen in culture on both murine microglia and a murine macrophage cell line, RAW 264.7. Since IL-5 is known to be secreted by both microglia and astrocytes in response to inflammatory stimuli, these results indicate that IL-5 may be involved in the cytokine-immune cascades leading to microglia proliferation in areas affected by disease and tissue damage.}, Author = {Ringheim, G. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Tumor Necrosis Factor;Interleukins;Interleukin-5;Mitogens;Granulocyte-Macrophage Colony-Stimulating Factor;Cell Division;11 Glia;Microglia;Animals, Newborn;Mice;Animals;Cerebral Cortex;Bromodeoxyuridine;Endotoxins}, Medline = {96274817}, Month = {12}, Nlm_Id = {7600130}, Number = {2}, Organization = {Neuroscience Therapeutic Domain, Hoechst-Roussel Pharmaceuticals, Inc., Somerville, NJ 08876, USA.}, Pages = {131-4}, Pii = {0304394095121536}, Pubmed = {8848235}, Title = {Mitogenic effects of interleukin-5 on microglia}, Uuid = {DF39CAAC-E779-4BCE-B61B-3BA7BEB63732}, Volume = {201}, Year = {1995}} @article{Riolobos:2001, Abstract = {The long-term effect of transplanting embryonic frontal cortex into a unilateral frontal cortex lesion has been studied in adult rats. Before surgery, activity in an open field, muscular strength of both forelimbs, and performance in a paw-reaching-for-food task were scored in 26 rats. In 21 animals a unilateral cortex lesion was then made in the forelimb motor area of the hemisphere contralateral to the preferred paw in the paw-reaching-for-food task, while the other 5 animals were sham-operated. On retesting, the lesion animals changed the preferred paw. A solid homotopic transplant of embryonic tissue (embryonic day 17) was then placed in the lesion cavity in 11 of the lesion rats. Three months later neither lesion alone nor lesion plus transplantation affected open field behavior and muscular strength, but the lesion permanently affected performance in the paw-reaching-for-food task, as shown by a change of preferred paw and a functional deficit in the paw contralateral to the lesion. Transplantation ameliorated the deficits caused by the lesion, but this was only evident when animals were forced to reach with the paw contralateral to the lesion plus transplant. The behavioral results were independent of the size of the lesion and graft. Connections between graft and host tissue were studied by means of the fluorescent tracer 1,1'-dioctadecyl-3,3,3'3'-tetramethylindocarbocyanine perchlorate (DiI). A dense array of labeled fibers was found in the host cortex adjacent to the transplant. The results suggest that functional recovery depends on grafting but is only evident when the animal is obliged to use the affected limb.}, Author = {Riolobos, A. S. and Heredia, M. and de la Fuente, J. A. and Criado, J. M. and Yajeya, J. and Campos, J. and Santacana, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1074-7427}, Journal = {Neurobiol Learn Mem}, Keywords = {Movement Disorders;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Behavior, Animal;Motor Cortex;Rats;Rats, Wistar;Transplantation, Homologous;Recovery of Function;Forelimb;Muscle, Skeletal;Animals;Male;Fetal Tissue Transplantation;Frontal Lobe}, Medline = {21198233}, Month = {5}, Nlm_Id = {9508166}, Number = {3}, Organization = {Departamento de Fisiolog{\'\i}a y Farmacolog{\'\i}a, Universidad de Salamanca, Madrid, Spain.}, Pages = {274-92}, Pii = {S1074742700939790}, Pubmed = {11300734}, Title = {Functional recovery of skilled forelimb use in rats obliged to use the impaired limb after grafting of the frontal cortex lesion with homotopic fetal cortex}, Uuid = {0100E08D-B20C-4A2D-AB23-57A6ECC39DBE}, Volume = {75}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/nlme.2000.3979}} @article{Rioult-Pedotti:1998, Abstract = {Learning a new motor skill requires an alteration in the spatiotemporal pattern of muscle activation. Motor areas of cerebral neocortex are thought to be involved in this type of learning, possibly by functional reorganization of cortical connections. Here we show that skill learning is accompanied by changes in the strength of connections within adult rat primary motor cortex (M1). Rats were trained for three or five days in a skilled reaching task with one forelimb, after which slices of motor cortex were examined to determine the effect of training on the strength of horizontal intracortical connections in layer II/III. The amplitude of field potentials in the forelimb region contralateral to the trained limb was significantly increased relative to the opposite 'untrained'hemisphere. No differences were seen in the hindlimb region. Moreover, the amount of long-term potentiation (LTP) that could be induced in trained M1 was less than in controls, suggesting that the effect of training was at least partly due to LTP-like mechanisms. These data represent the first direct evidence that plasticity of intracortical connections is associated with learning a new motor skill. 1097-6256 Journal Article}, Author = {Rioult-Pedotti, M. S. and Friedman, D. and Hess, G. and Donoghue, J. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Nat Neurosci}, Keywords = {18 Classic Neuroanatomy Physiology;Reference Values;Motor Cortex/*physiology;Rats, Sprague-Dawley;Learning/*physiology;Neuronal Plasticity/physiology;Female;Rats;Action Potentials/physiology;Neural Pathways/physiology;Long-Term Potentiation/physiology;Motor Skills/*physiology;M;Support, U.S. Gov't, P.H.S.;Forelimb/physiology;Support, Non-U.S. Gov't;Animals}, Number = {3}, Organization = {Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.}, Pages = {230-4}, Pubmed = {10195148}, Title = {Strengthening of horizontal cortical connections following skill learning}, Uuid = {705E6842-DB5D-4E3B-975E-8D05ECFD6EC5}, Volume = {1}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10195148}} @article{Rispeter:1997, Abstract = {The synthesis of long cDNA molecules encoding the complete genome of RNA viruses has recently been demonstrated; this major improvement has numerous practical applications such as construction of infectious cDNA clones or study of sequence variability at the level of a single RNA molecule. Using hepatitis C virus (HCV) as a model, we established an RT-PCR technique for amplification of cDNA fragments with a length of about 5 kb. The RT reaction was carried out with a Moloney murine leukaemia virus reverse transcriptase lacking detectable RNase H activity. For PCR reactions an enzyme mix containing Taq and Pwo DNA polymerases was used. Hot start and addition of 5\%DMSO were also important to efficiently achieve long PCR products. About 10(6) HCV genome equivalents/ml in serum were needed in order to amplify the HCV genome in only two cDNA fragments covering about 98\%of the complete genome. Analysis of the HCV quasi-species is also possible by this method as shown by sequencing of the hypervariable region 1 (HVR1) after cloning of cDNAs. The integrity of the long cDNA clones was proven by (1) restriction analyses, (2) partial sequencing and (3) expression of respective gene products. In vitro transcribed cDNAs were translated in rabbit reticulocyte lysate. Structural and nonstructural HCV proteins were identified by immunoprecipitation using patient serum. These results suggest that the two cDNA clones encode a complete and functional open reading frame of HCV. 0022-1317 Journal Article}, Author = {Rispeter, K. and Lu, M. and Lechner, S. and Zibert, A. and Roggendorf, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Gen Virol}, Keywords = {Hepacivirus/*genetics;*Genome, Viral;Molecular Sequence Data;Human;EE, DMSO, abstr;08 Aberrant cell cycle;Amino Acid Sequence;Rabbits;DNA, Complementary/*genetics;Support, Non-U.S. Gov't;Animals;Cloning, Molecular;Open Reading Frames/*genetics;Polymerase Chain Reaction}, Organization = {Institut fur Virologie, Universitatsklinikum Essen, Germany.}, Pages = {2751-9}, Pubmed = {9367360}, Title = {Cloning and characterization of a complete open reading frame of the hepatitis C virus genome in only two cDNA fragments}, Uuid = {8E2807D6-96BB-46C3-928D-E570178CE1A4}, Volume = {78 ( Pt 11)}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9367360}} @article{Rivera:1999, Abstract = {GABA (gamma-aminobutyric acid) is the main inhibitory transmitter in the adult brain, and it exerts its fast hyperpolarizing effect through activation of anion (predominantly Cl-)-permeant GABA(A) receptors. However, during early neuronal development, GABA(A)-receptor-mediated responses are often depolarizing, which may be a key factor in the control of several Ca2+-dependent developmental phenomena, including neuronal proliferation, migration and targeting. To date, however, the molecular mechanism underlying this shift in neuronal electrophysiological phenotype is unknown. Here we show that, in pyramidal neurons of the rat hippocampus, the ontogenetic change in GABA(A)-mediated responses from depolarizing to hyperpolarizing is coupled to a developmental induction of the expression of the neuronal (Cl-)-extruding K+/Cl- co-transporter, KCC2. Antisense oligonucleotide inhibition of KCC2 expression produces a marked positive shift in the reversal potential of GABAA responses in functionally mature hippocampal pyramidal neurons. These data support the conclusion that KCC2 is the main Cl- extruder to promote fast hyperpolarizing postsynaptic inhibition in the brain.}, Author = {Rivera, C. and Voipio, J. and Payne, J. A. and Ruusuvuori, E. and Lahtinen, H. and Lamsa, K. and Pirvola, U. and Saarma, M. and Kaila, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {gamma-Aminobutyric Acid;Cell Differentiation;Electrophysiology;Animals;Gene Expression Regulation, Developmental;Carrier Proteins;Rats;Symporters;research support, u.s. gov't, p.h.s. ;Chlorides;in vitro ;Hippocampus;Pyramidal Cells;RNA, Messenger;Blotting, Southern;Reverse Transcriptase Polymerase Chain Reaction;research support, non-u.s. gov't ;Potassium;21 Neurophysiology;Muscimol;24 Pubmed search results 2008;Guinea Pigs;GABA Agonists}, Month = {1}, Nlm_Id = {0410462}, Number = {6716}, Organization = {Department of Biosciences, University of Helsinki, Finland.}, Pages = {251-5}, Pubmed = {9930699}, Title = {The K+/Cl- co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation}, Uuid = {B4EFA1F3-042E-4E70-A436-D09BCBD7D6FF}, Volume = {397}, Year = {1999}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/16697}} @article{Rivest:2006, Abstract = {Microglia are the resident immune cells of the brain, and they are under permanent activity to patrol the cerebral microenvironment. A proper inhibitory feedback onto these cells is critical during both intact and injury conditions. In this issue of Neuron, Eljaschewitsch and colleagues report that such feedback is provided by the endogenous cannabinoid anandamine and CB(1/2) receptor signaling, which ultimately leads to mitogen-activated protein kinase phosphatase-1 (MKP-1) induction. MKP-1 interferes with lipopolysaccharide-induced toll-like receptor 4 signaling and limits brain damage due to exaggerated microglial reactivity following acute NMDA injury.}, Author = {Rivest, Serge}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {24 Pubmed search results 2008;Feedback, Biochemical;Microglia;11 Glia;Cannabinoids;comment;Animals;Brain;Humans;Cytoprotection;Immune System}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, 2705, boul. Laurier, Qu{\'e}bec , Canada G1V-4G2.}, Pages = {4-8}, Pii = {S0896-6273(05)01050-0}, Pubmed = {16387633}, Title = {Cannabinoids in microglia: a new trick for immune surveillance and neuroprotection}, Uuid = {2AB98EA6-BBF3-49ED-BDEE-F1C933473734}, Volume = {49}, Year = {2006}, url = {papers/Rivest_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.12.004}} @article{Rizvi:2006, Abstract = {Transplanted adult bone marrow-derived cells (BMDCs) have been shown to adopt the phenotype and function of several nonhematopoietic cell lineages and promote tumorigenesis. Beyond its cancer enhancing potential, cell fusion has recently emerged as an explanation of how BMDCs regenerate diseased heptocytes, contribute to Purkinje neurons and skeletal and cardiac muscle cells, and participate in skin and heart regeneration. Although bone marrow-derived epithelial cells also have been observed in the intestine, fusion as a mechanism has not been investigated. Here, we show that transplanted BMDCs fuse with both normal and neoplastic intestinal epithelium. Long-term repopulation by donor-derived cells was detected in all principal intestinal epithelial lineages including enterocytes, goblet cells, Paneth cells, and enteroendocrine cells, suggesting that the fusion partners of the BMDCs are long-lived intestinal progenitors or stem cells. Fusion of BMDCs with neoplastic epithelium did not result in tumor initiation. Our findings suggest an unexpected role for BMDCs in both regeneration and tumorigenesis of the intestine.}, Author = {Rizvi, and Swain, and Davies, and Bailey, and Decker, and Willenbring, and Grompe, and Fleming, and Wong,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {7505876}, Organization = {Departments of Surgery, Dermatology, Cell and Developmental Biology, and Molecular and Medical Genetics, Center for Hematologic Malignancies, Division of Hematology and Medical Oncology, and Oregon Cancer Institute, Oregon Stem Cell Center, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239.}, Pii = {0508593103}, Pubmed = {16606845}, Title = {Bone marrow-derived cells fuse with normal and transformed intestinal stem cells}, Uuid = {2AFA34E2-01FB-4B7B-89B8-7AA2D38ADC6E}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0508593103}} @article{Robbe:2006, Abstract = {Cannabinoids impair hippocampus-dependent memory in both humans and animals, but the network mechanisms responsible for this effect are unknown. Here we show that the cannabinoids Delta(9)-tetrahydrocannabinol and CP55940 decreased the power of theta, gamma and ripple oscillations in the hippocampus of head-restrained and freely moving rats. These effects were blocked by a CB1 antagonist. The decrease in theta power correlated with memory impairment in a hippocampus-dependent task. By simultaneously recording from large populations of single units, we found that CP55940 severely disrupted the temporal coordination of cell assemblies in short time windows (<100 ms) yet only marginally affected population firing rates of pyramidal cells and interneurons. The decreased power of local field potential oscillations correlated with reduced temporal synchrony but not with firing rate changes. We hypothesize that reduced spike timing coordination and the associated impairment of physiological oscillations are responsible for cannabinoid-induced memory deficits.}, Author = {Robbe, David and Montgomery, Sean M. and Thome, Alexander and Rueda-Orozco, Pavel E. and McNaughton, Bruce L. and Buzsaki, Gy{\"o}rgy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9809671}, Number = {12}, Organization = {Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, Newark, New Jersey 07102, USA.}, Pages = {1526-33}, Pii = {nn1801}, Pubmed = {17115043}, Title = {Cannabinoids reveal importance of spike timing coordination in hippocampal function}, Uuid = {2629C796-B55B-4B0C-A13C-EA8F73C668EF}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1801}} @article{Roberts:1987, Abstract = {We have previously observed that lysosomes redistribute from their normal location in neuronal cell bodies to the dendrites following an intracerebroventricular injection of an antimitotic such as colchicine, vinblastine or vincristine. In the present study, we have followed the developmental distribution of lysosomes in the brains of untreated rats, using a lysosomal marker enzyme, dipeptidylaminopeptidase II. A relatively high concentration of neuronal lysosomes was found in the dendrites of olfactory bulb mitral cell neurons and in hippocampal granule and pyramidal cell neurons from postnatal day 1 (P1) to P8. As the animals matured, the pattern of lysosomal enzyme distribution was reversed. Lysosomes became progressively less concentrated in the dendrites and more concentrated in neuronal cell bodies. In cerebellar Purkinje cells, lysosomes were only found in the cell bodies during the first week after birth. Between P9 and P19, lysosomes appeared in the dendrites of these neurons and, with maturity, progressively disappeared from the dendrites and were concentrated mainly in cell bodies. The presence of lysosomes in the dendrites of developing animals suggests that the transport of lysosomes to the dendrites, induced by microtubule poisons, mimics a physiological process which is normally present during development. eng Journal Article}, Author = {Roberts, V. J. and Gorenstein, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Journal = {Dev Neurosci}, Keywords = {F abstr;10 Development;Purkinje Cells/ultrastructure;Rats, Inbred F344;Rats;Lysosomes/*ultrastructure;Hippocampus/cytology/ultrastructure;Time Factors;Olfactory Bulb/cytology/ultrastructure;Brain/cytology/growth &development/*ultrastructure;Animal;Neurons/*ultrastructure;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't}, Number = {4}, Organization = {Department of Pharmacology, University of California, Irvine.}, Pages = {255-64.}, Title = {Examination of the transient distribution of lysosomes in neurons of developing rat brains}, Uuid = {A693B572-36D9-4DBC-91F9-C1ADB0B568F2}, Volume = {9}, Year = {1987}} @article{Roberts:2000, Abstract = {We describe a new mutation, flathead (fh), that arose spontaneously in an inbred colony of Wistar rats. The mutation is autosomal recessive, and the behavioral phenotype of fh/fh rats includes spontaneous seizures, tremor, impaired coordination, and premature death. A striking feature of the fh mutation is a dramatic reduction in brain size (40\%of normal at birth). In contrast, no abnormalities are evident in the peripheral nervous system or in other tissues outside of the CNS. Although bromodeoxyuridine incorporation assays indicate that the rate of cell proliferation in the fh/fh cortex is similar to that of unaffected animals, in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin end-labeling assays reveal a dramatic increase in apoptotic cell death beginning after embryonic day 16 (E16). At E18 there is a 20-fold increase in cell death in the ventricular zone of fh/fh neocortex, and at postnatal day 1 (P1), the number of apoptotic cells is still two times that of normal. However, by P8 the extent of cell death in fh/fh is comparable to that of unaffected littermates, indicating that the reduction in brain growth is caused by abnormally high apoptosis during a discrete developmental period. Late-developing structures such as the cerebellum, neocortex, hippocampus, and retina are most severely affected by the fh mutation. Within these structures, later-generated neuronal populations are selectively depleted. Together, these results suggest that the flathead gene is essential for a developmental event required for the generation and maturation of late-born cell populations in the brain. 1529-2401 Journal Article}, Author = {Roberts, M. R. and Bittman, K. and Li, W. W. and French, R. and Mitchell, B. and LoTurco, J. J. and D'Mello, S. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {J Neurosci}, Keywords = {Cerebellum/abnormalities/cytology/embryology;Animals;Genes, Recessive;Rats;Epilepsy/diagnosis/genetics;Retina/abnormalities/cytology/embryology;Mutation;Seizures/diagnosis/genetics;Rats, Wistar;Antimetabolites;Purkinje Cells/chemistry/cytology;CK;Brain/*abnormalities/cytology/*embryology;Calcium-Binding Protein, Vitamin D-Dependent/analysis;Hippocampus/abnormalities/cytology/embryology;Neocortex/abnormalities/cytology/embryology;Rats, Mutant Strains/*abnormalities;Cell Division/genetics;In Situ Nick-End Labeling;Apoptosis/*genetics;Bromodeoxyuridine;Electroencephalography}, Number = {6}, Organization = {Department of Physiology, University of Connecticut, Storrs, Connecticut 06269, USA.}, Pages = {2295-306}, Pubmed = {10704505}, Title = {The flathead mutation causes CNS-specific developmental abnormalities and apoptosis}, Uuid = {A8A9AA60-69F0-11DA-A4B6-000D9346EC2A}, Volume = {20}, Year = {2000}, url = {papers/Roberts_JNeurosci2000.pdf}} @article{Roberts:2006, Abstract = {CNS abnormalities can be detected during chronic human immunodeficiency virus (HIV) infection, before the development of opportunistic infections or other sequelae of immunodeficiency. However, although end-stage dementia caused by HIV has been linked to the presence of infected and activated macrophages and microglia in the brain, the nature of the changes resulting in the motor and cognitive disorders in the chronic stage is unknown. Using simian immunodeficiency virus-infected rhesus monkeys, we sought the molecular basis for CNS dysfunction. In the chronic stable stage, nearly 2 years after infection, all animals had verified CNS functional abnormalities. Both virus and infiltrating lymphocytes (CD8+ T-cells) were found in the brain. Molecular analysis revealed that the expression of several immune response genes was increased, including CCL5, which has pleiotropic effects on neurons as well as immune cells. CCL5 was significantly upregulated throughout the course of infection, and in the chronic phase was present in the infiltrating lymphocytes. We have identified an altered state of the CNS at an important stage of the viral-host interaction, likely arising to protect against the virus but in the long term leading to damaging processes.}, Author = {Roberts, Eleanor S. and Huitron-Resendiz, Salvador and Taffe, Michael A. and Marcondes, Maria Cecilia G. and Flynn, Claudia T. and Lanigan, Caroline M. and Hammond, Jennifer A. and Head, Steven R. and Henriksen, Steven J. and Fox, Howard S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {17}, Organization = {Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California, 92037, USA.}, Pages = {4577-85}, Pii = {26/17/4577}, Pubmed = {16641237}, Title = {Host response and dysfunction in the CNS during chronic simian immunodeficiency virus infection}, Uuid = {C70D5895-A396-4391-A041-985F1FB8FC14}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4504-05.2006}} @article{Roche:2006, Abstract = {The vesicular stomatitis virus has an atypical membrane fusion glycoprotein (G) exhibiting a pH-dependent equilibrium between two forms at the virus surface. Membrane fusion is triggered during the transition from the high- to low-pH form. The structure of G in its low-pH form shows the classic hairpin conformation observed in all other fusion proteins in their postfusion conformation, in spite of a novel fold combining features of fusion proteins from classes I and II. The structure provides a framework for understanding the reversibility of the G conformational change. Unexpectedly, G is homologous to gB of herpesviruses, which raises important questions on viral evolution.}, Author = {Roche, St{\'e}phane and Bressanelli, St{\'e}phane and Rey, F{\'e}lix A. and Gaudin, Yves}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Viral Fusion Proteins;Protein Subunits;Models, Molecular;Protein Folding;Vesicular stomatitis-Indiana virus;Crystallography, X-Ray;Mutation;Evolution, Molecular;15 Retrovirus mechanism;Hydrogen-Ion Concentration;Protein Structure, Secondary;Viral Envelope Proteins;Protein Conformation;Membrane Glycoproteins;Protein Structure, Tertiary;Protein Structure, Quaternary;24 Pubmed search results 2008;Amino Acid Sequence;Molecular Sequence Data;15 PS VSVG receptor;Crystallization;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {0404511}, Number = {5784}, Organization = {CNRS, Unit{\'e} Mixte de Recherche (UMR) 2472, Institut F{\'e}d{\'e}ratif de Recherche (IFR) 115, Virologie Mol{\'e}culaire et Structurale, 91198, Gif sur Yvette, France.}, Pages = {187-91}, Pii = {313/5784/187}, Pubmed = {16840692}, Title = {Crystal structure of the low-pH form of the vesicular stomatitis virus glycoprotein G}, Uuid = {88AE12A5-4333-11DB-A5D2-000D9346EC2A}, Volume = {313}, Year = {2006}, url = {papers/Roche_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1127683}} @article{Rochefort:2002, Abstract = {In the mammalian forebrain, most neurons originate from proliferating cells in the ventricular zone lining the lateral ventricles, including a discrete area of the subventricular zone (SVZ). In this region, neurogenesis continues into adulthood. Most of the cells generated in the SVZ are neuronal precursors with progeny that migrate rostrally along a pathway known as the rostral migratory stream before they reach the main olfactory bulb (MOB) where they differentiate into local interneurons. The olfactory system thus provides an attractive model to investigate neuronal production and survival, processes involving interplay between genetic and epigenetic influences. The present study was conducted to investigate whether exposure to an odor-enriched environment affects neurogenesis and learning in adult mice. Animals housed in either a standard or an odor-enriched environment for 40 d were injected intraperitoneally with bromodeoxyuridine (BrdU) to detect proliferation among progenitor cells and to follow their survival in the MOB. The number of BrdU-labeled neurons was not altered 4 hr after a single BrdU injection. In contrast, the number of surviving progenitors 3 weeks after BrdU injection was markedly increased in animals housed in an enriched environment. This effect was specific because enriched odor exposure did not influence hippocampal neurogenesis. Finally, we showed that adult mice housed in odor- enriched cages display improved olfactory memory without a change in spatial learning performance. By maintaining a constitutive turnover of granule cells subjected to modulation by environmental cues, ongoing bulbar neurogenesis could be associated with improved olfactory memory.}, Author = {Rochefort, C. and Gheusi, G. and Vincent, J. D. and Lledo, P. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:57 -0400}, Journal = {J Neurosci}, Keywords = {B pdf}, Number = {7}, Organization = {Perception and Memory Laboratory, Centre National de la Recherche Scientifique Unite de Recherche Associee 2182, Institut Pasteur, 75 724 Paris Cedex 15, France.}, Pages = {2679-89.}, Title = {Enriched odor exposure increases the number of newborn neurons in the adult olfactory bulb and improves odor memory}, Uuid = {56191CD2-CDEF-11D9-B244-000D9346EC2A}, Volume = {22}, Year = {2002}, url = {papers/Rochefort_JNeurosci2002.pdf}} @article{Roe:1993, Abstract = {In synchronized rat or mouse cells infected with Moloney murine leukemia virus (MLV), integration of viral DNA and production of viral proteins occur only after the cells traverse mitosis. Integration is blocked when cells are prevented from progressing through mitosis. Viral nucleoprotein complexes isolated from arrested cells contain full-length viral DNA and can integrate this viral DNA in vitro, showing that the block to integration in arrested cells is not due to a lack of mature integration machinery. When infected cells traverse mitosis, there is a sharp increase in nuclear accumulation of viral DNA. The dependence of integration on mitosis may therefore be due to a requirement for mitosis and nuclear envelope breakdown for entry of the viral integration complex into the nucleus. 0261-4189 Journal Article}, Author = {Roe, T. and Reynolds, T. C. and Yu, G. and Brown, P. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {Embo J}, Keywords = {Animals;Cells, Cultured;Rats;J abstr;*Mitosis;Metaphase;*Virus Integration;15 Retrovirus mechanism;G2 Phase;Viral Proteins/biosynthesis;Support, Non-U.S. Gov't;Genome, Viral;DNA, Viral/*metabolism;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Moloney murine leukemia virus/genetics/*physiology;Mice;Cell Nucleus/metabolism;Nucleoproteins/metabolism}, Number = {5}, Organization = {Department of Biochemistry, Stanford University, CA 94305.}, Pages = {2099-108}, Pubmed = {8491198}, Title = {Integration of murine leukemia virus DNA depends on mitosis}, Uuid = {892E779B-EA2C-11DA-920C-000D9346EC2A}, Volume = {12}, Year = {1993}, url = {papers/Roe_EmboJ1993.pdf}} @article{Roelink:2000, Abstract = {Recent genetic studies have shown that the signalling factor Wnt3a is required for formation of the hippocampus; the developmental consequences of Wnt signalling in the hippocampus are mediated by multiple HMG-box transcription factors, with LEF-1 being required just for formation of the dentate gyrus.}, Author = {Roelink, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {DNA-Binding Proteins;10 Development;Hippocampus;10 Hippocampus;Embryonic Induction;Mice, Mutant Strains;review, tutorial;High Mobility Group Proteins;Animals;Mice;Proteins;review;Transcription Factors}, Medline = {20219677}, Month = {4}, Nlm_Id = {9107782}, Number = {7}, Organization = {Department of Biological Structure, Center for Developmental Biology, University of Washington, Box 357420, Seattle, 98117-7420, USA. roelink\@u.washington.edu}, Pages = {R279-81}, Pii = {S0960-9822(00)00407-3}, Pubmed = {10753739}, Title = {Hippocampus formation: an intriguing collaboration}, Uuid = {8EBD90A3-D863-4504-8195-41AD1561A067}, Volume = {10}, Year = {2000}, url = {papers/Roelink_CurrBiol2000.pdf}} @article{Roelofs:2005, Abstract = {Human glial fibrillary acidic protein-delta (GFAP-delta) is a GFAP protein isoform that is encoded by an alternative splice variant of the GFAP-gene. As a result, GFAP-delta protein differs from the predominant splice form, GFAP-alpha, by its C-terminal protein sequence. In this study, we show that GFAP-delta protein is not expressed by all GFAP-expressing astrocytes but specifically by a subpopulation located in the subpial zone of the cerebral cortex, the subgranular zone of the hippocampus, and, most intensely, by a ribbon of astrocytes following the ependymal layer of the cerebral ventricles. Therefore, at least in the sub ventricular zone (SVZ), GFAP-delta specifically marks the population of astrocytes that contain the neural stem cells in the adult human brain. Interestingly, the SVZ astrocytes actively splice GFAP-delta transcripts, in contrast to astrocytes adjacent to this layer. Furthermore, we show that GFAP-delta protein, unlike GFAP-alpha, is not upregulated in astrogliosis. Our data therefore indicate a different functional role for GFAP-delta in astrocyte physiology. Finally, transfection studies showed that GFAP-delta protein expression has a negative effect on GFAP filament formation, and therefore could be important for modulating intermediate filament cytoskeletal properties, possibly facilitating astrocyte motility. Further studies on GFAP-delta and the cells that express it are important for gaining insights into its function during differentiation, migration and during health and disease. (c) 2005 Wiley-Liss, Inc.}, Author = {Roelofs, and Fischer, and Houtman, and Sluijs, and Van Haren, and Van Leeuwen, and Hol,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {8806785}, Organization = {Netherlands Institute for Brain Research, Graduate School Neurosciences, Amsterdam, the Netherlands.}, Pubmed = {16001427}, Title = {Adult human subventricular, subgranular, and subpial zones contain astrocytes with a specialized intermediate filament cytoskeleton}, Uuid = {1F144850-F432-4BF3-96EB-58C567FCD672}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20243}} @article{Roerig:2000, Abstract = {A growing body of evidence suggests that highly correlated, spontaneous neural activity plays an important role in shaping connections in the developing nervous system prior to the maturation of sensory afferents. In this article we discuss the mechanisms involved in the generation and the regulation of spontaneous activity patterns in the developing retina and the developing neocortex. Spontaneous activity in the developing retina propagates across the ganglion cell layer as waves of action potentials and drives rhythmic increases in intracellular calcium in retinal neurons. Retinal waves are mediated by a combination of chemical synaptic transmission and gap junctions, and the circuitry responsible for generating retinal waves changes with age and between species. In the developing cortex, spontaneous calcium elevations propagate across clusters of cortical neurons called domains. Cortical domains are generated by a regenerative mechanism involving second messenger diffusion through gap junctions and subsequent calcium release from internal stores. The neocortical gap junction system is regulated by glutamate-triggered second messenger systems as well as neuromodulatory transmitters, suggesting extensive interactions between synaptic transmission and information flow through gap junctions. The interaction between gap junctions and chemical synaptic transmission observed in these developing networks represent a powerful mechanism by which activity across large groups of neurons can be correlated.}, Author = {Roerig, B. and Feller, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0165-0173}, Journal = {Brain Res Brain Res Rev}, Keywords = {Synapses;Gap Junctions;21 Neurophysiology;Neural Pathways;Neurotransmitter Agents;Animals;24 Pubmed search results 2008;Neurons;review}, Month = {4}, Nlm_Id = {8908638}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, School of Medicine, University of Maryland, Baltimore, MD, USA.}, Pages = {86-114}, Pii = {S0165017399000697}, Pubmed = {10751659}, Title = {Neurotransmitters and gap junctions in developing neural circuits}, Uuid = {1BCB8C17-81C8-41D0-B1F1-EA16DFFD42D8}, Volume = {32}, Year = {2000}, url = {papers/Roerig_BrainResBrainResRev2000.pdf}} @article{Rogers:1992, Abstract = {Many dopaminergic cells of the substantia nigra are known to contain the calcium-binding proteins calretinin and calbindin-D28k. Catecholaminergic cell groups throughout the rat brain were therefore examined by two-colour immunofluorescence to determine whether they too contained these calcium-binding proteins as well as tyrosine hydroxylase (TH). Some TH+ cell groups are mostly positive for both calretinin and calbindin, notably in the ventral tegmental area, the interfascicular nucleus, and parts of the substantia nigra. Other TH+ cell groups in the midbrain, hindbrain and hypothalamus are very diverse; different cell groups are positive for calretinin, or calbindin, or both, or neither. In the olfactory bulb, entirely separate sets of periglomerular cells are positive for TH, calretinin and calbindin. However, there is considerable heterogeneity in calcium- binding protein expression within most cell groups, even in the substantia nigra. This could be a sign that calcium-binding proteins are regulated according to aspects of neuronal activity.}, Author = {Rogers, J. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Brain Res}, Keywords = {I;Brain/*metabolism;Rats;Immunohistochemistry;Calcium-Binding Protein, Vitamin D-Dependent/immunology/*metabolism;Biological Markers;Tyrosine 3-Monooxygenase/immunology/*metabolism;In Vitro;Antibodies, Monoclonal/immunology;Brain Mapping;Animal;Support, Non-U.S. Gov't;Catecholamines/metabolism;13 Olfactory bulb anatomy}, Number = {2}, Organization = {Department of Physiology, University of Cambridge, UK.}, Pages = {203-10.}, Title = {Immunohistochemical markers in rat brain: colocalization of calretinin and calbindin-D28k with tyrosine hydroxylase}, Uuid = {49DA0CF2-47F3-44E2-A30C-033991A275C0}, Volume = {587}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=1356063}} @article{Rogers:1997, Abstract = {For an understanding of the aberrant biology seen in mouse mutations and identification of more subtle phenotype variation, there is a need for a full clinical and pathological characterization of the animals. Although there has been some use of sophisticated techniques, the majority of behavioral and functional analyses in mice have been qualitative rather than quantitative in nature. There is, however, no comprehensive routine screening and testing protocol designed to identify and characterize phenotype variation or disorders associated with the mouse genome. We have developed the SHIRPA procedure to characterize the phenotype of mice in three stages. The primary screen utilizes standard methods to provide a behavioral and functional profile by observational assessment. The secondary screen involves a comprehensive behavioral assessment battery and pathological analysis. These protocols provide the framework for a general phenotype assessment that is suitable for a wide range of applications, including the characterization of spontaneous and induced mutants, the analysis of transgenic and gene-targeted phenotypes, and the definition of variation between strains. The tertiary screening stage described is tailored to the assessment of existing or potential models of neurological disease, as well as the assessment of phenotypic variability that may be the result of unknown genetic influences. SHIRPA utilizes standardized protocols for behavioral and functional assessment that provide a sensitive measure for quantifying phenotype expression in the mouse. These paradigms can be refined to test the function of specific neural pathways, which will, in turn, contribute to a greater understanding of neurological disorders.}, Author = {Rogers, D. C. and Fisher, E. M. and Brown, S. D. and Peters, J. and Hunter, A. J. and Martin, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0938-8990}, Journal = {Mamm Genome}, Keywords = {Variation (Genetics);24 Pubmed search results 2008;23 Technique;Behavior, Animal;Phenotype;Neural Pathways;Genome;Animals;Genetics, Behavioral;Mice;Nervous System Diseases;Research Design}, Month = {10}, Nlm_Id = {9100916}, Number = {10}, Organization = {SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Harlow, UK.}, Pages = {711-3}, Pubmed = {9321461}, Title = {Behavioral and functional analysis of mouse phenotype: SHIRPA, a proposed protocol for comprehensive phenotype assessment}, Uuid = {D007B8FB-DBAA-4A24-ACA8-EF10B16CE24D}, Volume = {8}, Year = {1997}} @article{Rolls:2007, Abstract = {Neurogenesis - the formation of new neurons in the adult brain - is considered to be one of the mechanisms by which the brain maintains its lifelong plasticity in response to extrinsic and intrinsic changes. The mechanisms underlying the regulation of neurogenesis are largely unknown. Here, we show that Toll-like receptors (TLRs), a family of highly conserved pattern-recognizing receptors involved in neural system development in Drosophila and innate immune activity in mammals, regulate adult hippocampal neurogenesis. We show that TLR2 and TLR4 are found on adult neural stem/progenitor cells (NPCs) and have distinct and opposing functions in NPC proliferation and differentiation both in vitro and in vivo. TLR2 deficiency in mice impaired hippocampal neurogenesis, whereas the absence of TLR4 resulted in enhanced proliferation and neuronal differentiation. In vitro studies further indicated that TLR2 and TLR4 directly modulated self-renewal and the cell-fate decision of NPCs. The activation of TLRs on the NPCs was mediated via MyD88 and induced PKCalpha/beta-dependent activation of the NF-kappaB signalling pathway. Thus, our study identified TLRs as players in adult neurogenesis and emphasizes their specified and diverse role in cell renewal.}, Author = {Rolls, Asya and Shechter, Ravid and London, Anat and Ziv, Yaniv and Ronen, Ayal and Levy, Rinat and Schwartz, Michal}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {100890575}, Number = {9}, Organization = {Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.}, Pages = {1081-8}, Pii = {ncb1629}, Pubmed = {17704767}, Title = {Toll-like receptors modulate adult hippocampal neurogenesis}, Uuid = {C80F8CFC-0C25-4742-A433-EC0EBA995E2B}, Volume = {9}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb1629}} @article{Romanko:2004, Abstract = {Perinatal hypoxic-ischemic (H/I) brain injury remains a major cause of neurologic disability. Because we have previously demonstrated that this insult depletes cells from the subventricular zone (SVZ), the goal of the present investigation was to compare the relative vulnerability to H/I of neural stem cells versus progenitors. The dorsolateral SVZs of P6 rats were examined at 2 to 48 hours of recovery from H/I using hematoxylin and eosin, in situ end labeling (ISEL), terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL), electron microscopy, and immunofluorescence. Pyknotic nuclei and ISEL cells were observed by 4 hours of recovery, peaked at 12 hours, and persisted for at least 48 hours. Many active-caspase-3 cells were observed at 12 hours and they comprised one third of the total TUNEL population. Electron microscopy revealed that hybrid cell deaths predominated at 12 hours of recovery. Importantly, few dying cells were observed in the medial SVZ, where putative stem cells reside, and no nestin medial SVZ cells showed caspase-3 activation. By contrast, active-caspase-3/PSA-NCAM progenitors were prominent in the lateral SVZ. These data demonstrate that early progenitors are vulnerable to H/I, whereas neural stem cells are resilient. The demise of these early progenitors may lead to the depletion of neuronal and late oligodendrocyte progenitors, contributing to cerebral dysgenesis after perinatal insults. 0271-678x Journal Article}, Author = {Romanko, M. J. and Rothstein, R. P. and Levison, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Cereb Blood Flow Metab}, Keywords = {C, D abstr;04 Adult neurogenesis factors}, Number = {7}, Organization = {Department of Neural and Behavioral Sciences, Pennsylvania State University, College of Medicine, Hershey, Pennsylvania 17033, USA.}, Pages = {814-25}, Pubmed = {15241190}, Title = {Neural stem cells in the subventricular zone are resilient to hypoxia/ischemia whereas progenitors are vulnerable}, Uuid = {E1FE6A7C-6FF7-42AC-B789-C95BF40A084D}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15241190}} @article{Romijn:1994, Abstract = {The aim of this study was to investigate whether the rat cerebral cortex, damaged by hypoxia-ischemia in early postnatal life, would show an increased seizure susceptibility and/or spontaneous epileptic discharges in adulthood. To that end 12-13-day-old Wistar rat pups were unilaterally exposed to hypoxic-ischemic conditions. After a recovery period of about 2.5 months, recording and stimulation electrodes were permanently implanted over the left and right fronto-parietal neocortex. Long-term recording of baseline electrocortical activity showed that only those animals that had incurred severe brain damage, as was reflected by the presence of a cortical infarction, ran a high risk of developing permanent epileptic activity. With the aid of the stimulation electrodes the initial threshold for localized seizure activity was found to be the same for the experimental and non-treated groups. However, when the kindling-like decline of this threshold was assessed by repeated testing over a 2-week period, the infarcted animals tended to a more rapid decline but a higher stabilization level than the non-infarcted and control animals.}, Author = {Romijn, H. J. and Voskuyl, R. A. and Coenen, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Electric Stimulation;Animals;Rats;Seizures;Brain;21 Epilepsy;Female;Epilepsy;Rats, Wistar;Male;Animals, Newborn;Hypoxia, Brain;Cerebral Cortex;21 Neurophysiology;Brain Ischemia;24 Pubmed search results 2008;Electroencephalography;Research Support, Non-U.S. Gov't}, Medline = {94229038}, Month = {1}, Nlm_Id = {8703089}, Number = {1}, Organization = {Netherlands Institute for Brain Research, Amsterdam.}, Pages = {31-42}, Pubmed = {8174523}, Title = {Hypoxic-ischemic encephalopathy sustained in early postnatal life may result in permanent epileptic activity and an altered cortical convulsive threshold in rat}, Uuid = {3B114799-E770-449D-83EF-13D97B049247}, Volume = {17}, Year = {1994}} @article{Root:1983, Abstract = {Weanling albino rats were fed semisynthetic diets deficient or sufficient in vitamin B6 or copper, or both, for 2 or 3 months. Brains were examined by light and electron microscopy after Golgi impregnation or conventional tissue processing for electron microscopy. Golgi impregnation revealed that some pyramidal cells of the cerebral cortex, particularly in layers III and V, showed partial to nearly complete dendritic loss. This occurred in all deficient groups but was most typical of deficiency of vitamin B6. Swelling in dendrites or perikarya was more typical of copper deficiency. Ultrastructural observation revealed large vacuoles in cellular processes of the cerebral cortex in deficient groups. The hippocampus of copper-deficient rats contained dark, apparently degenerating processes while axonal swellings were seen in vitamin B6 deficiency. These abnormalities are discussed as evidence for accelerated aging of neurons related to poor nutritional status.}, Author = {Root, E. J. and Longenecker, J. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0002-9165}, Journal = {Am J Clin Nutr}, Keywords = {Pyridoxine;Copper;Aging;10 Development;Research Support, Non-U.S. Gov't;Dendrites;Neuroglia;Golgi Apparatus;Rats;Hippocampus;Vitamin B 6 Deficiency;10 Structural plasticity;Animals;Brain;Male;Cerebral Cortex;24 Pubmed search results 2008}, Medline = {83175466}, Month = {4}, Nlm_Id = {0376027}, Number = {4}, Pages = {540-52}, Pubmed = {6837489}, Title = {Brain cell alterations suggesting premature aging induced by dietary deficiency of vitamin B6 and/or copper}, Uuid = {C301DC44-DEF8-4679-A06E-1D85CA52922F}, Volume = {37}, Year = {1983}} @article{Roper:1997, Abstract = {Cortical dysplasia, a disorder of neuronal migration, has a strong association with intractable epilepsy in humans but little is known about the physiologic abnormalities that are present in this condition. Fetal rats were exposed to external irradiation to experimentally produce diffuse cortical dysplasia. In vitro neocortical slices from adult irradiated and control animals were examined in physiologic solution and in the presence of the A-type gamma-amino butyric acid (GABAA) receptor antagonist, bicuculline methiodide. Epileptiform bursts were quantified by counting the number of negative field potentials per epileptiform event. In the presence of bicuculline, neocortical slices with cortical dysplasia demonstrated more robust epileptiform activity in the form of an increased number of negative field potentials per epileptiform event. This demonstrates that areas of experimentally induced cortical dysplasia possess an inherent hyperexcitability when GABAA-mediated inhibition is effectively blocked.}, Author = {Roper, S. N. and King, M. A. and Abraham, L. A. and Boillot, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:55 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Epilepsy;21 Epilepsy;Rats, Sprague-Dawley;21 Dysplasia-heterotopia;21 Neurophysiology;Bicuculline;Action Potentials;Rats;Neural Inhibition;In Vitro;Research Support, U.S. Gov't, Non-P.H.S.;Animals;Brain;GABA Antagonists;Cerebral Cortex;24 Pubmed search results 2008}, Medline = {97273245}, Month = {3}, Nlm_Id = {8703089}, Number = {3}, Organization = {Department of Neurological Surgery, University of Florida College of medicine, Gainesville 32610-0265, USA. roper\@neocortex.health.ufl.edu}, Pages = {443-9}, Pii = {S0920121196010145}, Pubmed = {9127725}, Title = {Disinhibited in vitro neocortical slices containing experimentally induced cortical dysplasia demonstrate hyperexcitability}, Uuid = {124F1A2B-C609-4EC9-9C71-9CFB02B71EAE}, Volume = {26}, Year = {1997}, url = {papers/Roper_EpilepsyRes1997.pdf}} @article{Roper:1998, Abstract = {Certain developmental abnormalities of the cerebral cortex are closely associated with epilepsy in humans. Exposure of fetal rats to external gamma-irradiation produces diffuse cortical dysplasia and neuronal heterotopia. These abnormalities are the result of radiation-induced cell death coupled with continued cortical development in an altered cellular environment. In vivo electroencephalography studies in these animals have revealed an increased propensity for electrographic seizures in the presence of the sedating agents, acepromazine and xylazine. In vitro neocortical slices containing dysplastic cortex demonstrate enhanced excitability, as compared to control neocortex, when inhibition that is mediated by the A-type gamma-amino butyric acid receptor is blocked with bicuculline methiodide. In utero irradiation of rats produces structural changes that mimic some aspects of cerebral dysgenesis in humans and results in physiologic changes that increase the animals' propensity for seizures. Similarities and differences between the animal model and the human syndromes are discussed.}, Author = {Roper, S. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:55 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Gamma Rays;10 Development;Pregnancy;Animals;Humans;Rats;Seizures;21 Epilepsy;review;Female;Epilepsy;Disease Models, Animal;Receptors, GABA-A;Cerebral Cortex;Neurons;21 Neurophysiology;10 genetics malformation;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Choristoma;Electroencephalography}, Medline = {98432476}, Month = {9}, Nlm_Id = {8703089}, Number = {1-2}, Organization = {Department of Neurological Surgery, University of Florida, Gainesville 32610-0265, USA. roper\@neocortex.health.ufl.edu}, Pages = {63-74}, Pii = {S0920-1211(98)00040-0}, Pubmed = {9761309}, Title = {In utero irradiation of rats as a model of human cerebrocortical dysgenesis: a review}, Uuid = {1AA680A3-5662-4EA3-BD16-FC282BDD70B4}, Volume = {32}, Year = {1998}, url = {papers/Roper_EpilepsyRes1998.pdf}} @article{Rose:2001, Author = {Rose, C. R. and Konnerth, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008;Biological Clocks;21 Neurophysiology;Cell Communication;Astrocytes;Calcium Channels;comment;Calcium Signaling;Animals;Humans;Receptors, Neurotransmitter;review;Neurons}, Medline = {21370267}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Pages = {773-4}, Pii = {90464}, Pubmed = {11477417}, Title = {Exciting glial oscillations}, Uuid = {B0BDFD1D-C38C-49AC-89BB-F299F2D62ED7}, Volume = {4}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/90464}} @article{Rose:2001a, Abstract = {Activation of most excitatory synapses of central neurons produces calcium release signals from intracellular stores. Synaptically evoked calcium release from stores is frequently triggered by the binding of glutamate to metabotropic receptors and the subsequent activation of IP(3) receptors in spines and dendrites. There is increasing evidence for the presence of local calcium signals caused by calcium-induced calcium release (CICR) through activation of ryanodine or IP(3) receptors. Recent work on mutant mice indicates that store signaling determines activity-dependent synaptic plasticity.}, Author = {Rose, C. R. and Konnerth, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Synapses;Purkinje Cells;21 Neurophysiology;Neuronal Plasticity;Pyramidal Cells;Calcium;Animals;24 Pubmed search results 2008;review}, Medline = {21432016}, Month = {8}, Nlm_Id = {8809320}, Number = {4}, Organization = {Institute of Physiology, Ludwig-Maximilians University of Munich, 80336 Munich, Germany.}, Pages = {519-22}, Pii = {S0896-6273(01)00402-0}, Pubmed = {11545711}, Title = {Stores not just for storage. intracellular calcium release and synaptic plasticity}, Uuid = {3E7720DD-AA9C-4318-AE37-6B89DAE9E762}, Volume = {31}, Year = {2001}} @article{Rosen:1996, Abstract = {Freezing injury to the cortical plate of the newborn rat results in the formation of a focal region of cerebrocortical microdysgenesis resembling, in many ways, human 4-layered microgyria. Previous research has shown that neurons born during embryonic day (E) 20 migrate through the initial damage and take their place in the cell-dense layer of the microgyric lesion. The current study was conducted to determine: (1) whether neurons generated earlier in development would be found in microgyric cortex; and (2) whether the freezing injury would stimulate production of neurons postnatally. Rat pups from mothers who were injected with S-phase markers on E15, E17, E19, and E21 were subjected to freezing injury of the cortex to induce microgyria on postnatal day (P) 1. Other pups received a freezing lesion and then pulse or cumulative injections of S-phase markers for the next 72 h. Neurons born on E17 and E19 were found scattered throughout the cell-dense layer of the microgyric cortex. Early (E15) generated neurons were nearly absent in the microgyric cortex, and there was no evidence of postnatal induction of cortical neurogenesis. These results are considered in light of recent work demonstrating postnatal neocortical neurogenesis in response to early neocortical injury.}, Author = {Rosen, G. D. and Sherman, G. F. and Galaburda, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Animals;Humans;Aging;Rats;Brain;21 Epilepsy;Rats, Wistar;Disease Models, Animal;Embryonic and Fetal Development;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Cerebral Cortex;Neurons;Freezing;21 Neurophysiology;Cell Division;24 Pubmed search results 2008;S Phase}, Medline = {96440073}, Month = {7}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Dyslexia Research Laboratory, Beth Israel Hospital, Boston, MA 02215, USA. glenn\_rosen\@bih.harvard.edu}, Pages = {71-8}, Pii = {0006-8993(96)00351-4}, Pubmed = {8842384}, Title = {Birthdates of neurons in induced microgyria}, Uuid = {10F5FA39-45AA-4B0B-988E-E81A3C3A8DB0}, Volume = {727}, Year = {1996}} @article{Rosen:2000, Abstract = {Injury to the developing cortical plate can result in a variety of neuronal migration disorders. The results are reported of experimental research aimed at determining whether these different types of neocortical malformations are the consequence of comparable injury of varying intensity. Freezing probes were placed on the skulls of 44 newborn rats (age equivalent to 4 to 5 months of gestation in humans) and induced either one or two freezing injuries of durations ranging from 2 to 20 seconds. A variety of cortical malformations including minor laminar dysplasias, molecular layer ectopias, microgyria, and porencephalic cysts were seen in the brains of these animals when they were examined on postnatal day (P)2, P21, and P60. The severity of the malformation was directly related to the strength (number of hits and duration) of the freezing injury. These results suggest that a single etiologic event of varying severity during neuronal migration to the neocortex can induce widely disparate malformations of the cortex.}, Author = {Rosen, G. D. and Galaburda, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0012-1622}, Journal = {Dev Med Child Neurol}, Keywords = {Animals;24 Pubmed search results 2008;21 Epilepsy;21 Neurophysiology;Rats;Female;Research Support, U.S. Gov't, P.H.S.;Rats, Wistar;Pregnancy;Animals, Newborn;Male;Disease Models, Animal;Cerebral Cortex;Neurons;Cell Movement}, Medline = {20535742}, Month = {10}, Nlm_Id = {0006761}, Number = {10}, Organization = {Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. grosen\@caregroup.harvard.edu}, Pages = {652-62}, Pubmed = {11085292}, Title = {Single cause, polymorphic neuronal migration disorders: an animal model}, Uuid = {5FB999AB-A9FA-4223-9A72-5D944DE09876}, Volume = {42}, Year = {2000}} @article{Roskams:2005, Author = {Roskams, A. Jane and Tetzlaff, Wolfram}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cell Differentiation;17 Transplant Regeneration;Spinal Cord Injuries;Stem Cells;comment;Animals;Humans;24 Pubmed search results 2008;Stem Cell Transplantation;review}, Month = {6}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Zoology and ICORD (International Collaboration on Repair Discoveries), University of British Columbia, 6270 University Boulevard, Vancouver, BC, Canada V6T 1Z4.}, Pages = {267-72}, Pii = {S0014-4886(05)00047-6}, Pubmed = {15869930}, Title = {Directing stem cells and progenitor cells on the stage of spinal cord injury}, Uuid = {A2207411-142F-48C5-B0D8-8135492C7E13}, Volume = {193}, Year = {2005}, url = {papers/Roskams_ExpNeurol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.expneurol.2005.01.023}} @article{Ross:2003, Abstract = {Transcription factors with bHLH motifs modulate critical events in the development of the mammalian neocortex. Multipotent cortical progenitors are maintained in a proliferative state by bHLH factors from the Id and Hes families. The transition from proliferation to neurogenesis involves a coordinate increase in the activity of proneural bHLH factors (Mash1, Neurogenin1, and Neurogenin2) and a decrease in the activity of Hes and Id factors. As development proceeds, inhibition of proneural bHLH factors in cortical progenitors promotes the formation of astrocytes. Finally, the formation of oligodendrocytes is triggered by an increase in the activity of bHLH factors Olig1 and Olig2 that may be coupled with a decrease in Id activity. Thus, bHLH factors have key roles in corticogenesis, affecting the timing of differentiation and the specification of cell fate. 0896-6273 Journal Article Review Review, Tutorial}, Author = {Ross, S. E. and Greenberg, M. E. and Stiles, C. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Neuron}, Keywords = {Astrocytes/cytology;Cell Differentiation/*physiology;10 Development;Neurons/cytology;Multipotent Stem Cells/physiology;Cell Lineage/*physiology;Human;F both;Neocortex/*cytology/*embryology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;Oligodendroglia/cytology;Helix-Loop-Helix Motifs/*physiology;Transcription Factors/chemistry/physiology}, Number = {1}, Organization = {Division of Neuroscience, Children's Hospital, Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {13-25}, Pubmed = {12848929}, Title = {Basic helix-loop-helix factors in cortical development}, Uuid = {36BF42F3-BEB0-4C96-925A-8A8B26C0C946}, Volume = {39}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12848929}} @article{Rossi:2002, Abstract = {There is a pressing need for treatments for neurodegenerative diseases. Hopes have been raised by the prospect of neural stem cell therapy; however, despite intense research activities and media attention, stem cell therapy for neurological disorders is still a distant goal. Effective strategies must be developed to isolate, enrich and propagate homogeneous populations of neural stem cells, and to identify the molecules and mechanisms that are required for their proper integration into the injured brain. This article examines these requirements, discusses the results obtained so far, and considers the steps that need to be taken to provide instruction to donor cells and to elucidate the neurogenic potential of the adult central nervous system environment. 1471-003x Journal Article Review Review, Tutorial}, Author = {Rossi, F. and Cattaneo, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:57 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {*Stem Cell Transplantation;17 Transplant Regeneration;Human;Nervous System Diseases/pathology/*therapy;Cell Differentiation/physiology;Neurons/physiology/*transplantation;Stem Cells/physiology;L pdf;Animals;Support, Non-U.S. Gov't}, Number = {5}, Organization = {Rita Levi Montalcini Center for Brain Repair, Department of Neuroscience, Section of Physiology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy. ferdinando.rossi\@unito.it}, Pages = {401-9}, Title = {Opinion: neural stem cell therapy for neurological diseases: dreams and reality}, Uuid = {0D076052-DD04-4EE6-8D26-7B5F9DBBE14B}, Volume = {3}, Year = {2002}, url = {papers/Rossi_NatRevNeurosci2002.pdf}} @article{Rossner:2004, Author = {Rossner, Mike and Yamada, Kenneth M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {Image Processing, Computer-Assisted;Software;Research;Ethics;Publishing;24 Pubmed search results 2008;news}, Month = {7}, Nlm_Id = {0375356}, Number = {1}, Pages = {11-5}, Pii = {jcb.200406019}, Pubmed = {15240566}, Title = {What's in a picture? The temptation of image manipulation}, Uuid = {B7DD0EFD-F85C-498F-A8CD-3D29B9849D51}, Volume = {166}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200406019}} @article{Rothkamm:2003, Abstract = {Little is known about the quantitative contributions of nonhomologous end joining (NHEJ) and homologous recombination (HR) to DNA double-strand break (DSB) repair in different cell cycle phases after physiologically relevant doses of ionizing radiation. Using immunofluorescence detection of gamma-H2AX nuclear foci as a novel approach for monitoring the repair of DSBs, we show here that NHEJ-defective hamster cells (CHO mutant V3 cells) have strongly reduced repair in all cell cycle phases after 1 Gy of irradiation. In contrast, HR-defective CHO irs1SF cells have a minor repair defect in G(1), greater impairment in S, and a substantial defect in late S/G(2). Furthermore, the radiosensitivity of irs1SF cells is slight in G(1) but dramatically higher in late S/G(2), while V3 cells show high sensitivity throughout the cell cycle. These findings show that NHEJ is important in all cell cycle phases, while HR is particularly important in late S/G(2), where both pathways contribute to repair and radioresistance. In contrast to DSBs produced by ionizing radiation, DSBs produced by the replication inhibitor aphidicolin are repaired entirely by HR. irs1SF, but not V3, cells show hypersensitivity to aphidicolin treatment. These data provide the first evaluation of the cell cycle-specific contributions of NHEJ and HR to the repair of radiation-induced versus replication-associated DSBs. 0270-7306 Journal Article}, Author = {Rothkamm, K. and Kruger, I. and Thompson, L. H. and Lobrich, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Mol Cell Biol}, Keywords = {Hamsters;Animals;Bromodeoxyuridine/pharmacology;Phenotype;Cell Cycle;CHO Cells;08 Aberrant cell cycle;Microscopy, Fluorescence;EE;Time Factors;Cell Line;*Recombination, Genetic;G2 Phase;Support, Non-U.S. Gov't;Flow Cytometry;Support, U.S. Gov't, Non-P.H.S.;*DNA Damage;Antimetabolites, Antineoplastic/pharmacology;G1 Phase;S Phase;Cell Nucleus/metabolism;Dose-Response Relationship, Radiation;*DNA Repair}, Number = {16}, Organization = {Fachrichtung Biophysik, Universitat des Saarlandes, D-66421 Homburg/Saar, Germany.}, Pages = {5706-15}, Pubmed = {12897142}, Title = {Pathways of DNA double-strand break repair during the mammalian cell cycle}, Uuid = {A9330763-EE5C-4DBB-AC1A-EB58A888A159}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12897142}} @article{Rothstein:2004, Abstract = {1087-0156 Comment News}, Author = {Rothstein, J. D. and Snyder, E. Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Nat Biotechnol}, Keywords = {T abstr;23 Technique}, Number = {3}, Pages = {283-5}, Pubmed = {14990948}, Title = {Reality and immortality--neural stem cells for therapies}, Uuid = {88085D72-580F-4AD2-9EC7-982D570F1C66}, Volume = {22}, Year = {2004}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14990948}} @article{Rotshenker:2003, Abstract = {Microglia and macrophages play critical roles in the response of the central and peripheral nervous systems (CNS and PNS, respectively) to injury and disease, one of which is the removal of degenerated myelin by phagocytosis. Myelin removal is efficient during Wallerian degeneration, which follows injury to PNS axons, and in CNS autoimmune demyelinating diseases (e.g., multiple sclerosis) but is inefficient after injury to CNS axons. We suggest that inefficient myelin removal results from deficient microglia activation, reflected by the failure to up-regulate Galectin-3/MAC-2 expression, which marks a state of activation correlated with efficient myelin phagocytosis. Surprisingly, whether or not executing myelin phagocytosis, CNS microglia express the alphaM/beta2 integrin complement receptor-3 (CR3/MAC-1), which has the potential of mediating efficient myelin phagocytosis. We hypothesize that CR3/MAC-1 might be present in distinct inactive and active states that determine, respectively, efficient and inefficient CR3/MAC-1-mediated myelin phagocytosis. We present evidence that CR3/MAC-1-mediated myelin phagocytosis is regulated in microglia and macrophages. First, CR3/MAC-1- mediated myelin phagocytosis has complement-dependent and -independent components. Second, an active complement system augments CR3/MAC-1-mediated myelin phagocytosis. Third, anti-alphaM monoclonal antibodies (MAbs) inhibit and anti-beta2 MAbs augment CR3/MAC-1-mediated myelin phagocytosis in the presence and absence of an active complement system. Fourth, an active complement system modulates MAb-induced regulation of CR3/MAC-1-mediated myelin phagocytosis. Overall, MAb-induced phagocytosis regulation might range three- to sevenfold from inefficient to efficient. We suggest that one of the mechanisms underlying MAb-induced phagocytosis regulation is the induction/stabilization of inactive and active conformational changes. Monoclonal antibody-induced phagocytosis regulation must reveal a mechanism by which native extracellular molecules bind to and regulate CR3/MAC-1-mediated myelin phagocytosis in microglia and macrophages.}, Author = {Rotshenker, Shlomo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0895-8696}, Journal = {J Mol Neurosci}, Keywords = {Not relevant;11 Glia}, Medline = {22863582}, Nlm_Id = {9002991}, Number = {1}, Organization = {Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School and the Eric Roland Center for Neurodegenerative Diseases, POB 12272, Jerusalem 91120, Israel. ROTSH\@md.huji.ac.il}, Pages = {65-72}, Pii = {JMN-21-1-65}, Pubmed = {14500997}, Title = {Microglia and macrophage activation and the regulation of complement-receptor-3 (CR3/MAC-1)-mediated myelin phagocytosis in injury and disease}, Uuid = {B377DFC1-08BC-459B-94B9-EAAD9ADAE423}, Volume = {21}, Year = {2003}} @article{Rouiller:1990, Abstract = {The interconnections of the auditory cortex with the parahippocampal and cingulate cortices were studied in the cat. Injections of the anterograde and retrograde tracer WGA-HRP were performed, in different cats (n = 9), in electrophysiologically identified auditory cortical fields. Injections in the posterior zone of the auditory cortex (PAF or at the PAF/AI border) labeled neurons and axonal terminal fields in the cingulate gyrus, mainly in the ventral bank of the splenial sulcus (a region that can be considered as an extension of the cytoarchitectonic area Cg), and posteriorly in the retrosplenial area. Labeling was also present in area 35 of the perirhinal cortex, but it was sparser than in the cingulate gyrus. Following WGA-HRP injection in AII, no labeling was found in the cingulate gyrus, but a few neurons and terminals were labeled in area 35. In contrast, no or very sparse labeling was observed in the cingulate and perirhinal cortices after WGA-HRP injections in the anterior zone of the auditory cortex (AI or AAF). A WGA-HRP injection in the cingulate gyrus labeled neurons in the posterior zone of the auditory cortex, between the posterior ectosylvian and the posterior suprasylvian sulci, but none was found more anteriorly in regions corresponding to AI, AAF and AII. The present data indicate the existence of preferential interconnections between the posterior auditory cortex and the limbic system (cingulate and parahippocampal cortices). This specialization of posterior auditory cortical areas can be related to previous observations indicating that the anterior and posterior regions of the auditory cortex differ from each other by their response properties to sounds and their pattern of connectivity with the auditory thalamus and the claustrum.}, Author = {Rouiller, E. M. and Innocenti, G. M. and De Ribaupierre, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Auditory Cortex;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Cats;Hippocampus;Neural Pathways;Not relevant;11 Glia;Animals;Wheat Germ Agglutinins;Horseradish Peroxidase;Support, Non-U.S. Gov't}, Medline = {90353487}, Nlm_Id = {0043312}, Number = {3}, Organization = {Institute of Physiology, University of Lausanne, Switzerland.}, Pages = {501-11}, Pubmed = {1696905}, Title = {Interconnections of the auditory cortical fields of the cat with the cingulate and parahippocampal cortices}, Uuid = {952E1948-A4A2-4EBA-A314-770E56F02091}, Volume = {80}, Year = {1990}} @article{Rousselot:1995, Abstract = {In the brain of adult mice, cell division persists in the subventricular zone (SVZ) of the lateral ventricles. These SVZ cells migrate rostrally 3-5 mm to the olfactory bulb, where they differentiate into neurons. We have investigated the distribution of PSA-N-CAM in the adult mouse forebrain. Immunoreactivity for PSA-N-CAM precisely reveals the migratory pathway of SVZ cells. This pathway of PSA-N-CAM positive cells starts in the lateral wall of the lateral ventricle, where immunopositive cells form weblike patterns. The PSA-N-CAM positive pathway extends rostrally between the corpus callosum and the striatum into the anterior ventral telencephalon, and then into the core of the olfactory bulb. Experiments in which [3H]-thymidine was injected systemically indicated that the majority of the dividing cells on the SVZ of the lateral ventricle and along the migratory pathway are positive to PSA-N-CAM or closely associated with PSA-N-CAM. Microinjection of [3H]-thymidine into the SVZ of the lateral ventricle to label a small patch of dividing SVZ cells shows that neuroblasts that migrated away from the injection site are positive or are closely associated with other cells that are positive for PSA-N-CAM. Migrating cells are tethered together, forming long chains of immunopositive cells. The migratory pathway is formed by 30-40 of these immunopositive chains. Radially oriented individual PSA-N-CAM positive cells were observed in the olfactory bulb. These cells seem to have broken away from chains of immunopositive cells in the core of the olfactory bulb and to be migrating to more superficial layers. Little is known about the mechanisms of tangential migration during development and in adulthood. The cell-cell arrangement revealed by PSA-N-CAM staining suggests new models for this form of neuronal migration. PSA-N-CAM localization along the migratory pathway to the olfactory bulb suggests that in the adult brain this molecule plays a role in migration of neuronal precursors. eng Journal Article}, Author = {Rousselot, P. and Lois, C. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Journal = {J Comp Neurol}, Keywords = {02 Adult neurogenesis migration;Cell Adhesion Molecules, Neuronal/*metabolism;Immunohistochemistry;Female;Models, Neurological;Thymidine/metabolism;Animal;Antibodies, Monoclonal/immunology;Cerebral Ventricles/*cytology;Pregnancy;B abstr;Olfactory Bulb/*cytology;Support, Non-U.S. Gov't;Mice;Neural Pathways/cytology;Male;Support, U.S. Gov't, P.H.S.}, Number = {1}, Organization = {Rockefeller University, New York, New York 10021.}, Pages = {51-61.}, Title = {Embryonic (PSA) N-CAM reveals chains of migrating neuroblasts between the lateral ventricle and the olfactory bulb of adult mice}, Uuid = {D6D89552-340A-4676-BBD5-3212FE00A70A}, Volume = {351}, Year = {1995}} @article{Rowland:1993, Abstract = {The frontal cortices of rats which received either D,L- or D-fenfluramine (DFEN) for 4 days were examined 18 h to 2 weeks following treatment for changes in synaptosomal uptake of serotonin (5HT), paroxetine binding, 5HT-immunoreactivity (5HT-IR), and both astrocytic (GFAP) and microglial markers. Additional rats received intracerebroventricular injections of the neurotoxin 5,7-dihydroxytryptamine (DHT). Consistent with previous reports, D,L- and DFEN produced dose-dependent losses of both 5HT uptake and paroxetine binding, and loss of 5HT-IR which coincided with an abnormal or 'swollen' appearance of immunoreactive axon processes. Recovery of these serotonergic indices was greatest following the lowest doses of DFEN, but was absent after 5,7-DHT treatment. No evidence for an increase in GFAP synthesis or microglial activation was observed in frontal cortices of rats treated with either DFEN or 5,7-DHT. We conclude that the presence of swollen 5HT-IR axons in the cortices of both the 5,7-DHT and DFEN groups is insufficient to trigger the glial responses often associated with neuronal degeneration. Thus, it remains to be determined if swollen 5HT-IR axons are a prelude to neurodegeneration, or whether they represent reversible changes in axonal immunochemistry associated with decreases in 5HT levels. The implications of the data for the clinical safety of DFEN are briefly discussed.}, Author = {Rowland, N. E. and Kalehua, A. N. and Li, B. H. and Semple-Rowland, S. L. and Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Dose-Response Relationship, Drug;Binding Sites;Animals;Rats;Microglia;Fenfluramine;Rats, Sprague-Dawley;Not relevant;11 Glia;Male;Support, Non-U.S. Gov't;Injections, Subcutaneous;Cerebral Cortex;Blotting, Western;Immunohistochemistry;Stereoisomerism;Administration, Oral;Serotonin}, Medline = {94073730}, Month = {10}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Department of Psychology, University of Florida, Gainesville 32611-2065.}, Pages = {35-43}, Pubmed = {8252414}, Title = {Loss of serotonin uptake sites and immunoreactivity in rat cortex after dexfenfluramine occur without parallel glial cell reactions}, Uuid = {E6841A16-0760-4309-BD09-17799DF1F6D3}, Volume = {624}, Year = {1993}} @article{Roy:2000, Abstract = {Neurogenesis persists in the adult mammalian hippocampus. To identify and isolate neuronal progenitor cells of the adult human hippocampus, we transfected ventricular zone-free dissociates of surgically-excised dentate gyrus with DNA encoding humanized green fluorescent protein (hGFP), placed under the control of either the nestin enhancer (E/nestin) or the Talpha1 tubulin promoter (P/Talpha1), two regulatory regions that direct transcription in neural progenitor cells. The resultant P/Talpha1:hGFP+ and E/nestin:enhanced (E)GFP+ cells expressed betaIII-tubulin or microtubule-associated protein-2; many incorporated bromodeoxyuridine, indicating their genesis in vitro. Using fluorescence-activated cell sorting, the E/nestin:EGFP+ and P/Talpha1:hGFP+ cells were isolated to near purity, and matured antigenically and physiologically as neurons. Thus, the adult human hippocampus contains mitotically competent neuronal progenitors that can be selectively extracted. The isolation of these cells may provide a cellular substrate for re-populating the damaged or degenerated adult hippocampus.}, Author = {Roy, N. S. and Wang, S. and Jiang, L. and Kang, J. and Benraiss, A. and Harrison-Restelli, C. and Fraser, R. A. and Couldwell, W. T. and Kawaguchi, A. and Okano, H. and Nedergaard, M. and Goldman, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Nat Med}, Keywords = {Human;Cells, Cultured;Neurons/*cytology/physiology;Transfection;Tubulin/*genetics;A-11;Dentate Gyrus/*cytology;01 Adult neurogenesis general;Luminescent Proteins/analysis/genetics;*Transcription, Genetic;Intermediate Filament Proteins/genetics;Support, Non-U.S. Gov't;Adult;Flow Cytometry;Support, U.S. Gov't, P.H.S.;Stem Cells/*cytology/physiology;Promoter Regions (Genetics);Hippocampus/*cytology}, Number = {3}, Organization = {Departments of Neurology and Neuroscience, Cornell University Medical College, 1300 York Ave. Room E607, New York, New York 10021, USA.}, Pages = {271-7.}, Title = {In vitro neurogenesis by progenitor cells isolated from the adult human hippocampus}, Uuid = {8A2EA8D8-1021-4FAD-940A-52C96AF49BDF}, Volume = {6}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10700228%20http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v3/n3/full/nm0300_271.html%20http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v3/n3/full//nm0300_271.html}} @article{Royce:1983, Abstract = {The retrograde fluorescent technique was used to label cortical neurons which project to both the caudate nucleus and also to the centromedian-parafascicular (CM-Pf) thalamic nuclear complex. After experimentation with many other pairs of fluorescent tracers, Evans Blue (EB) and Fast Blue (FB) were chosen as the best combination for studying the systems involved. Following injections of EB into the caudate nucleus and FB into the CM-Pf complex, doubly labeled medium-sized pyramidal neurons were present within layer V and VI of specific cortical regions. These cells were found on the inferior bank of the cruciate sulcus, in the anterior limbic area, in the cingulate and anterior sylvian gyri and within the buried cortex of the presylvian sulcus. The doubly labeled cells were relatively few in number compared to the more numerous singly labeled FB (corticothalamic) cells found in layers V and VI, and the very numerous singly labeled EB (corticostriatal) neurons, located in layers II, III, V, and VI.}, Author = {Royce, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Gyrus Cinguli;Staining and Labeling;research support, u.s. gov't, p.h.s. ;Thalamic Nuclei;21 Neurophysiology;Cats;Limbic System;Neural Pathways;21 Circuit structure-function;Brain Mapping;Animals;Caudate Nucleus;Cerebral Cortex;24 Pubmed search results 2008}, Nlm_Id = {0043312}, Number = {2-3}, Pages = {157-65}, Pubmed = {6196226}, Title = {Cortical neurons with collateral projections to both the caudate nucleus and the centromedian-parafascicular thalamic complex: a fluorescent retrograde double labeling study in the cat}, Uuid = {40E32702-6C81-450A-ADB5-02C69C4CC72D}, Volume = {50}, Year = {1983}} @article{Rozov:2001, Abstract = {1. In connections formed by nerve terminals of layer 2/3 pyramidal cells onto bitufted interneurones in young (postnatal day (P)14-15) rat somatosensory cortex, the efficacy and reliability of synaptic transmission were low. At these connections release was facilitated by paired-pulse stimulation (at 10 Hz). In connections formed by terminals of layer 2/3 pyramids with multipolar interneurones efficacy and reliability were high and release was depressed by paired-pulse stimulation. In both types of terminal, however, the voltage-dependent Ca2+ channels that controlled transmitter release were predominantly of the P/Q- and N-subtypes. 2. The relationship between unitary EPSP amplitude and extracellular calcium concentration ([Ca2+]o) was steeper for facilitating than for depressing terminals. Fits to a Hill equation with nH = 4 indicated that the apparent KD of the Ca2+ sensor for vesicle release was two- to threefold lower in depressing terminals than in facilitating ones. 3. Intracellular loading of pyramidal neurones with the fast and slowly acting Ca2+ buffers BAPTA and EGTA differentially reduced transmitter release in these two types of terminal. Unitary EPSPs evoked by pyramidal cell stimulation in bitufted cells were reduced by presynaptic BAPTA and EGTA with half-effective concentrations of approximately 0.1 and approximately 1 mM, respectively. Unitary EPSPs evoked in multipolar cells were reduced to one-half of control at higher concentrations of presynaptic BAPTA and EGTA (approximately 0.5 and approximately 7 mM, respectively). 4. Frequency-dependent facilitation of EPSPs in bitufted cells was abolished by EGTA at concentrations of > or = 0.2 mM, suggesting that accumulation of free Ca2+ is essential for facilitation in the terminals contacting bitufted cells. In contrast, facilitation was unaffected or even slightly increased in the terminals loaded with BAPTA in the concentration range 0.02-0.5 mM. This is attributed to partial saturation of exogenously added BAPTA. However, BAPTA at concentrations > or = 1 mM also abolished facilitation. 5. Frequency-dependent depression of EPSPs in multipolar cells was not significantly reduced by EGTA. With BAPTA, the depression decreased at concentrations > 0.5 mM, concomitant with a reduction in amplitude of the first EPSP in a train. 6. An analysis is presented that interprets the effects of EGTA and BAPTA on synaptic efficacy and its short-term modification during paired-pulse stimulation in terms of changes in [Ca2+] at the release site ([Ca2+]RS) and that infers the affinity of the Ca2+ sensor from the dependence of unitary EPSPs on [Ca2+]o. 7. The results suggest that the target cell-specific difference in release from the terminals on bitufted or multipolar cells can be explained by a longer diffusional distance between Ca2+ channels and release sites and/or lower Ca2+ channels density in the terminals that contact bitufted cells. This would lead to a lower [Ca2+] at release sites and would also explain the higher apparent K(D) of the Ca2+ sensor in facilitating terminals.}, Author = {Rozov, A. and Burnashev, N. and Sakmann, B. and Neher, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Presynaptic Terminals;Animals;Osmolar Concentration;Rats;Neural Pathways;Egtazic Acid;Neocortex;Synaptic Transmission;Neurotransmitter Agents;Reaction Time;Rats, Wistar;Pyramidal Cells;Calcium;21 Calcium imaging;21 Neurophysiology;Calcium Channels;Interneurons;24 Pubmed search results 2008;Intracellular Membranes;Buffers;Excitatory Postsynaptic Potentials}, Month = {3}, Nlm_Id = {0266262}, Number = {Pt 3}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut fur medizinische Forschung, Jahnstrasse 29, D-69120 Heidelberg, Germany.}, Pages = {807-26}, Pii = {PHY_11435}, Pubmed = {11251060}, Title = {Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics}, Uuid = {B95BB7FF-BE9F-4538-845F-100DE5168374}, Volume = {531}, Year = {2001}} @article{Rozovsky:1998, Abstract = {Astrocytes and microglia from cerebral cortex of 3-, 6-, 12-, and 24-month-old F344 male rat donors showed progressively greater proliferation during primary culture. Microglia from aging donor brains exhibited an amoeboid-like morphology and express antigens characteristic of an activated state (e.g., major histocompatibility complex class II). Moreover, microglia from aging donors were less sensitive to several types of regulators. Granulocyte-macrophage colony stimulating factor stimulated proliferation in microglia from young, but not aging brains. Transforming growth factor (TGF)-beta1 inhibited astrocytic and microglial proliferation in cultures from young, but not aging donors. Similarly, the inhibition of lipopolysaccharide-induced NO production by TGF-beta1 in microglia was impaired in cultures from 12-month (middle-age) brains. Another aging change detected by middle age, increased glial fibrillary acidic protein (GFAP) expression, also persisted in astrocytes from 12- to 24-month-old brains, as evaluated by increased activity of a 5'-upstream GFAP promoter construct. Thus, both microglia and astrocytes originated from aging cerebral cortex maintain in vitro at least some of the activated phenotypes of aging glia that are observed in vivo. This new in vitro cell model may allow efficient analysis of glial age changes.}, Author = {Rozovsky, I. and Finch, C. E. and Morgan, T. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0197-4580}, Journal = {Neurobiol Aging}, Keywords = {Animals;Astrocytes;Cells, Cultured;Aging;Rats;Transforming Growth Factor beta;Phenotype;Microglia;Thymidine;11 Glia;Male;Rats, Inbred F344;Support, Non-U.S. Gov't;Down-Regulation;Nitrogen;Support, U.S. Gov't, P.H.S.;Cell Division;Immunohistochemistry;Glial Fibrillary Acidic Protein}, Medline = {98221002}, Nlm_Id = {8100437}, Number = {1}, Organization = {Andrus Gerontology Center and Department of Biological Sciences University of Southern California, Los Angeles 90080-0191, USA.}, Pages = {97-103}, Pii = {S0197458097001693}, Pubmed = {9562510}, Title = {Age-related activation of microglia and astrocytes: in vitro studies show persistent phenotypes of aging, increased proliferation, and resistance to down-regulation}, Uuid = {E21496B7-4E6A-47EB-B2AD-EE116EAE1D01}, Volume = {19}, Year = {1998}} @article{Ruthazer:2005, Abstract = {The receptive field properties of neurons in the developing brain can in many cases be remarkably similar to those of adult neurons. This raises the question of why these same neurons need the capacity for such impressive developmental plasticity, most clearly demonstrated by the rewiring that occurs in response to sensory deprivation. The roles of developmental neuronal plasticity in the assimilation of neurons into a larger network, including temporal and cross-modal integration, are discussed.}, Author = {Ruthazer, Edward S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {21 Activity-development; 21 Neurophysiology;24 Pubmed search results 2008;Cell Differentiation;Models, Animal;21 Neurophysiology;Cell Communication;Neuronal Plasticity;Neural Pathways;Neural Inhibition;comment;Synaptic Transmission;Animals;Brain;Humans;review;Neurons}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.}, Pages = {825-8}, Pii = {S0896-6273(05)00203-5}, Pubmed = {15797544}, Title = {You're perfect, now change--redefining the role of developmental plasticity}, Uuid = {84E6A822-2D69-4B19-A0D6-524C69CD3805}, Volume = {45}, Year = {2005}, url = {papers/Ruthazer_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.03.008}} @article{Ryder:1990, Abstract = {Neural cell lines were produced by retroviral vector-mediated transduction of the avian myc oncogene. Target cells were mitotic progenitor cells of postnatal mouse olfactory bulb and cerebellum, and postnatal rat cerebral cortex. Infection of the first two areas, where neurogenesis and gliogenesis occur postnatally, produced multipotent clonal lines that exhibited phenotypes of both neuronal and glial cells, and one line with a stable neuronal phenotype. Infection of cerebral cortex, where gliogenesis, but not neurogenesis, occurs postnatally, generated mortal clones that exhibited cells of glial phenotype. These lines should prove valuable for both in vitro and in vivo studies aimed at understanding the control of cell fate and differentiation of neural progenitors. eng Journal Article}, Author = {Ryder, E. F. and Snyder, E. Y. and Cepko, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Journal = {J Neurobiol}, Keywords = {Cell Differentiation;*Transduction, Genetic;Rats;Neurons/*cytology;Cell Line, Transformed;Cerebellum/cytology;Animal;Stem Cells/cytology;23 Technique;*Cell Transformation, Viral;Genetic Vectors;Support, Non-U.S. Gov't;Retroviridae/genetics;Olfactory Bulb/cytology;T abstr;Support, U.S. Gov't, P.H.S.;Cerebral Cortex/cytology;Mice;Neuroglia/*cytology;*Oncogenes;Clone Cells}, Number = {2}, Organization = {Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.}, Pages = {356-75.}, Title = {Establishment and characterization of multipotent neural cell lines using retrovirus vector-mediated oncogene transfer}, Uuid = {866BDA71-71B9-4CA1-916E-EA9330F390F8}, Volume = {21}, Year = {1990}} @article{Rytting:1999, Abstract = {The development of a colorimetric capture assay for HIV-1 reverse transcriptase (RT) activity is described. This assay consisted of three basic steps: enzyme purification, RT reaction and product detection, which were all performed in the same microtitre plate. Mouse monoclonal anti-RT antibodies of subclass G2a were bound by polyclonal goat anti-(mouse IgG2a) immobilized in the wells of a microtitre plate. The monoclonal antibodies (mAbs) were selected for their ability to bind HIV-1 RT without hampering the polymerase activity. The assay system first involved the RT's adherence to the immobilized mAbs. Non-specific enzymes and other impurities were removed by a simple wash, after which an RT reaction mixture containing BrdUTP as nucleotide substrate was added. After the RT reaction substrate and product had been separated by washing of the plate, the amount of BrdUMP-DNA in the wells was finally detected with alkaline-phosphatase-conjugated mouse anti-BrdU antibodies of subclass IgG1. The background signal in this system was similar to the signals obtained with control wells coated with BSA only. A detection limit of 1.2 micro-units of RT activity, corresponding to 0.3 pg of RT protein, was obtained for the capture assay when applying colorimetric product detection. The assay detected RTs from HIV-1 subtypes A and B and one of the two D type isolates tested. None of the five non-HIV-1 RTs tested was found positive. At least 50 microl of human serum or plasma per sample could be included in the capture assay without adverse effects on the recovery of the RT activity.}, Author = {Rytting, A. S. and Akerblom, L. and Gronowitz, J. S. and K{\"a}llander, C. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0885-4513}, Journal = {Biotechnol Appl Biochem}, Keywords = {Colorimetry;Enzyme-Linked Immunosorbent Assay;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Antibodies, Monoclonal;Deoxyuracil Nucleotides;HIV-1 Reverse Transcriptase;15 Retrovirus mechanism;Animals;Enzymes, Immobilized;Bromodeoxyuridine;Isoenzymes;Mice}, Medline = {99268838}, Month = {6}, Nlm_Id = {8609465}, Organization = {Department of Genetics and Pathology, Section of Medical Genetics, Uppsala University, BMC, Box 578, SE-751 23 Uppsala, Sweden.}, Pages = {241-50}, Pubmed = {10334955}, Title = {Colorimetric capture assay for human-immunodeficiency-virus-I reverse transcriptase activity}, Uuid = {AEC61CA8-3169-4B5B-9069-12C795B5EBFF}, Volume = {29 ( Pt 3)}, Year = {1999}} @article{Ryzhova:2002, Abstract = {Simian immunodeficiency virus (SIV)-infected macaques develop an encephalitis (SIVE) that is pathologically virtually indistinguishable from that associated with HIV infection, with multinucleated giant cells (MNGCs) being the principal histopathological manifestation. To dissect SIV variants responsible for MNGC development, we examined the relationships between env sequences transcribed in individual MNGCs and those from genomic DNA of brain and spleen tissues. The brain-specific variant found in all brain clones was dominant among the clones from MNGCs, suggesting a role in the formation of giant cells. Furthermore, two additional minor groups of sequences were present in MNGCs. One group consisted of sequences closely related to those from spleen, indicating recent and probably multiple episodes of neuroinvasion. The second group represented clones similar or identical to the initial inoculum. The survival of archival sequences and their activation presumably by the fusion of productively and quiescently infected macrophages/microglia identify the central nervous system as a possible anatomical reservoir for latent infection.}, Author = {Ryzhova, Elena V. and Crino, Peter and Shawver, Linda and Westmoreland, Susan V. and Lackner, Andrew A. and Gonz{\'a}lez-Scarano, Francisco}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {RNA, Viral;Encephalitis, Viral;Animals;Virus Latency;Comparative Study;SIV;Brain;Sequence Alignment;Phylogeny;Female;Genes, env;11 Glia;Giant Cells;Male;Disease Models, Animal;Support, Non-U.S. Gov't;Macaca mulatta;Research Support, U.S. Gov't, P.H.S.;Simian Acquired Immunodeficiency Syndrome;Support, U.S. Gov't, P.H.S.;DNA, Viral;Amino Acid Sequence;Molecular Sequence Data;Spleen;Research Support, Non-U.S. Gov't}, Medline = {22080395}, Month = {5}, Nlm_Id = {0110674}, Number = {1}, Organization = {Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.}, Pages = {57-67}, Pii = {S0042682202913954}, Pubmed = {12083836}, Title = {Simian immunodeficiency virus encephalitis: analysis of envelope sequences from individual brain multinucleated giant cells and tissue samples}, Uuid = {807AA3FF-B780-4B8B-86F4-6F539A783522}, Volume = {297}, Year = {2002}} @article{Sabatini:2001, Abstract = {Dendritic spines are cellular microcompartments that are isolated from their parent dendrites and neighboring spines. Recently, imaging studies of spine Ca(2+) dynamics have revealed that Ca(2+) can enter spines through voltage-sensitive and ligand-activated channels, as well as through Ca(2+) release from intracellular stores. Relationships between spine Ca(2+) signals and induction of various forms of synaptic plasticity are beginning to be elucidated. Measurements of spine Ca(2+) concentration are also being used to probe the properties of single synapses and even individual calcium channels in their native environment.}, Author = {Sabatini, B. L. and Maravall, M. and Svoboda, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Signal Transduction;Purkinje Cells;Calcium Signaling;Animals;Humans;Rats;Neuronal Plasticity;Synaptic Transmission;review;Pyramidal Cells;Dendrites;Ion Transport;Action Potentials;Mice, Knockout;21 Neurophysiology;Cell Compartmentation;Calcium Channels;Mice;24 Pubmed search results 2008;Ion Channel Gating;Nerve Tissue Proteins;Receptors, N-Methyl-D-Aspartate;Rats, Mutant Strains}, Month = {6}, Nlm_Id = {9111376}, Number = {3}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11743, USA.}, Pages = {349-56}, Pii = {S0959-4388(00)00218-X}, Pubmed = {11399434}, Title = {Ca(2+) signaling in dendritic spines}, Uuid = {115BC240-63C6-4A57-9143-A5C4C6CF12FE}, Volume = {11}, Year = {2001}} @article{Sabatini:1996, Abstract = {Understanding the factors controlling synaptic delays has broad implications. On a systems level, the speed of synaptic transmission limits the communication rate between neurons and strongly influences local circuit dynamics. On a molecular level, the delay from presynaptic calcium entry to postsynaptic responses constrains the molecular mechanism of vesicle fusion. Previously it has not been possible to elucidate the determinants of synaptic delays in the mammalian central nervous system, where presynaptic terminals are small and difficult to study. We have developed a new approach to study timing at rat cerebellar synapses: we used optical techniques to measure voltage and calcium current simultaneously from presynaptic boutons while monitoring postsynaptic currents electrically. Here we report that the classic view that vesicle release is driven by calcium entry during action-potential repolarization holds for these synapses at room temperature, but not at physiological temperatures, where postsynaptic responses commence just 150 micros after the start of the presynaptic action potential. This brisk communication is a consequence of rapid calcium-channel kinetics, which allow significant calcium entry during the upstroke of the presynaptic action potential, and extremely fast calcium-driven vesicle fusion, which lags behind calcium influx by 60 micros.}, Author = {Sabatini, B. L. and Regehr, W. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Synapses;research support, u.s. gov't, p.h.s. ;Temperature;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;in vitro ;Models, Neurological;Calcium;Rats;Cerebellum;Synaptic Transmission;Reaction Time;Animals;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {0410462}, Number = {6605}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {170-2}, Pubmed = {8906792}, Title = {Timing of neurotransmission at fast synapses in the mammalian brain}, Uuid = {6E46D883-8E03-4502-B104-47A3E7191440}, Volume = {384}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/384170a0}} @article{Sabatini:2000, Abstract = {Most synapses form on small, specialized postsynaptic structures known as dendritic spines. The influx of Ca2+ ions into such spines--through synaptic receptors and voltage-sensitive Ca2+ channels (VSCCs)--triggers diverse processes that underlie synaptic plasticity. Using two-photon laser scanning microscopy, we imaged action-potential-induced transient changes in Ca2+ concentration in spines and dendrites of CA1 pyramidal neurons in rat hippocampal slices. Through analysis of the large trial-to-trial fluctuations in these transients, we have determined the number and properties of VSCCs in single spines. Here we report that each spine contains 1-20 VSCCs, and that this number increases with spine volume. We are able to detect the opening of a single VSCC on a spine. In spines located on the proximal dendritic tree, VSCCs normally open with high probability (approximately 0.5) following dendritic action potentials. Activation of GABA(B) receptors reduced this probability in apical spines to approximately 0.3 but had no effect on VSCCs in dendrites or basal spines. Our studies show that the spatial distribution of VSCC subtypes and their modulatory potential is regulated with submicrometre precision.}, Author = {Sabatini, B. L. and Svoboda, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Microscopy, Confocal;Synaptic Membranes;research support, u.s. gov't, p.h.s. ;Dendrites;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;in vitro ;Pyramidal Cells;Calcium Channels;Rats;Animals;Receptors, GABA-B;24 Pubmed search results 2008;Membrane Potentials}, Month = {11}, Nlm_Id = {0410462}, Number = {6812}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724, USA.}, Pages = {589-93}, Pubmed = {11117746}, Title = {Analysis of calcium channels in single spines using optical fluctuation analysis}, Uuid = {5D7B38A9-7A05-4027-BF77-47A7C6B2D88D}, Volume = {408}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35046076}} @article{Sadikot:1998, Abstract = {Neurotransmitters influence a wide variety of developmental processes. We hypothesize that N-methyl-D-aspartate (NMDA) glutamate receptors influence proliferation of populations of forebrain neurons. As our model, we use a subclass of GABAergic striatal interneurons that express the calcium binding protein parvalbumin (PV). To separate proliferative and post-proliferative effects of NMDA receptor antagonists on PV neurons, we first determined the birth-date of rat striatum PV neurons at the coronal level selected for analysis. Dividing striatal progenitor cells were marked by intraperitoneal injections of 5'-bromodeoxyuridine (BrdU) given to timed pregnant rats at selected time points between embryonic days (E) 12-22. Double immunohistochochemistry for BrdU and PV was used in adult progeny to determine the time course of neurogenesis of striatal PV neurons. The results of the neurogenetic analysis were then used for rational timing of treatment with competitive (CGS 19755) and non-competitive (MK-801) NMDA receptor antagonists. In comparison to pair-fed and vehicle- injected controls, gestational rats given CGS-19755 and MK-801 during the proliferative phase (E15-E18) showed a marked reduction of striatal PV neuron cell density as adults. In contrast, animals given NMDA antagonists during the post-proliferative period (E18-E21) showed no significant reduction in PV neuron cell density compared to pair-fed controls. These results suggest that glutamate influences cell proliferation of a population of striatal neurons by an NMDA-mediated mechanism, providing evidence for a novel role for excitatory amino acids in early forebrain development.}, Author = {Sadikot, A. F. and Burhan, A. M. and Belanger, M. C. and Sasseville, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Pregnancy;H;Dizocilpine Maleate/pharmacology;Cell Survival/drug effects;Rats;GABA/*physiology;Excitatory Amino Acid Antagonists/pharmacology;Female;Receptors, N-Methyl-D-Aspartate/*antagonists &inhibitors;Rats, Sprague-Dawley;Animal;Pipecolic Acids/pharmacology;Cell Count/drug effects;Male;Antimetabolites/diagnostic use;Support, Non-U.S. Gov't;Neostriatum/cytology/*physiology;Parvalbumins/metabolism;Immunohistochemistry;Bromodeoxyuridine/diagnostic use;Interneurons/*physiology;12 Interneuron development}, Number = {1}, Organization = {Department of Neurology and Neurosurgery, Montreal Neurological Institute McGill University, Quebec, Canada.}, Pages = {35-42.}, Title = {NMDA receptor antagonists influence early development of GABAergic interneurons in the mammalian striatum}, Uuid = {8ADCF13E-3E7E-4376-82F2-E42A4C3F7283}, Volume = {105}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9497077}} @article{Saenz:2004, Abstract = {The circumstances under which unintegrated lentivirus DNA can persist and be a functional template for transcription and protein expression are not clear. We constructed and validated the first class I (nonpleiotropic) integrase (IN) mutants for a non-human lentivirus (feline immunodeficiency virus [FIV]) and analyzed both these and known class I human immunodeficiency virus type 1 IN mutants. The FIV IN mutants (D66V and D66V/D118A) had class I properties: Gag/Pol precursor expression, proteolytic processing, particle formation, and reverse transcriptase (RT) production were normal, while the transduction of dividing fibroblasts was prevented and integration was blocked. When injected into rat retinas, the wild-type (WT) vector produced extensive, persistent transgene expression, compared with only rare positive neuronal cells for the IN mutant vector. In contrast, both WT and mutant vectors produced entirely equivalent, effective transduction levels of primary rat neurons (retinal ganglion cells). By testing the hypothesis that the unexpected retinal neuron transduction was related to cell cycle status, we found that when fibroblasts were growth arrested, transduction and internally promoted transgene expression were not inhibited at all by the class I FIV or HIV-1 IN mutations. Cells were then transduced under aphidicolin arrest and were released from the block 48 h later. Vector expression was stable and durable during repeated passaging in WT vector-transduced cells, while the release of cells transduced with equivalent RT units of class I IN mutant FIV or HIV vector resulted in a steady decline of expression, from 97 to 0\%of cells by day 10. Southern blot and PCR analyses showed a lack of integration, irrespective of cell cycle, for the class I mutants and an increase in one- and two-long terminal repeat circular and linear unintegrated DNAs in growth-arrested cells. We conclude that if cell division is prevented, unintegrated FIV and HIV-1 vector DNAs can produce high-level internally promoted transgene expression equivalent to WT vectors. The expression correlates with the unintegrated DNA levels. These observations may facilitate the study of the roles of IN and other preintegration complex components in preintegration phases of infection by (i) providing an alternative way to monitor unintegrated nuclear cDNA forms, (ii) restricting ascertainment to the transcriptionally functional subset of unintegrated DNA, (iii) enabling analysis in individual, nondividing cells, and (iv) uncoupling other potential functions of IN from integration.}, Author = {Saenz, Dyana T. and Loewen, Nils and Peretz, Mary and Whitwam, Todd and Barraza, Rom{\'a}n and Howell, Kyle G. and Holmes, Jonathan M. and Good, Margaret and Poeschla, Eric M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Research Support, Non-U.S. Gov't;Transduction, Genetic;Animals;Humans;Rats;Immunodeficiency Virus, Feline;Lentivirus;Sequence Alignment;Mutation;Rats, Sprague-Dawley;Integrases;15 Retrovirus mechanism;Hela Cells;Cell Line;Research Support, U.S. Gov't, P.H.S.;HIV Integrase;DNA, Viral;Virus Integration;24 Pubmed search results 2008;Amino Acid Sequence;Molecular Sequence Data;Cats;Retinal Ganglion Cells}, Month = {3}, Nlm_Id = {0113724}, Number = {6}, Organization = {Molecular Medicine Program, Departments of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.}, Pages = {2906-20}, Pubmed = {14990709}, Title = {Unintegrated lentivirus DNA persistence and accessibility to expression in nondividing cells: analysis with class I integrase mutants}, Uuid = {28D1163B-C204-4C7F-9A6B-3E1796D5A04C}, Volume = {78}, Year = {2004}} @article{Safo:2005, Abstract = {The long-term depression (LTD) of parallel fiber (PF) synapses onto Purkinje cells plays a central role in motor learning. Endocannabinoid release and LTD induction both depend upon activation of the metabotropic glutamate receptor mGluR1, require postsynaptic calcium increases, are synapse specific, and have a similar dependence on the associative activation of PF and climbing fiber synapses. These similarities suggest that endocannabinoid release could account for many features of cerebellar LTD. Here we show that LTD induction is blocked by a cannabinoid receptor (CB1R) antagonist, by inhibiting the synthesis of the endocannabinoid 2-arachidonyl glycerol (2-AG), and is absent in mice lacking the CB1R. Although CB1Rs are prominently expressed presynaptically at PF synapses, LTD is expressed postsynaptically. In contrast, a previously described transient form of inhibition mediated by endocannabinoids is expressed presynaptically. This indicates that Purkinje cells release 2-AG that activates CB1Rs to both transiently inhibit release and induce a postsynaptic form of LTD.}, Author = {Safo, Patrick K. and Regehr, Wade G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {gamma-Aminobutyric Acid;research support, n.i.h., extramural ;Electric Stimulation;Purkinje Cells;Synapses;Presynaptic Terminals;Rats;Animals;Patch-Clamp Techniques;Rats, Sprague-Dawley;in vitro ;Long-Term Depression (Physiology);Endocannabinoids;Lipoprotein Lipase;Receptor, Cannabinoid, CB2;Mice, Knockout;21 Neurophysiology;Arachidonic Acids;Cerebellum;Mice;24 Pubmed search results 2008;Glycerides;Neural Inhibition}, Month = {11}, Nlm_Id = {8809320}, Number = {4}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {647-59}, Pii = {S0896-6273(05)00787-7}, Pubmed = {16301180}, Title = {Endocannabinoids control the induction of cerebellar LTD}, Uuid = {B340D130-5743-4DCE-B504-1CF1D0CB3273}, Volume = {48}, Year = {2005}, url = {papers/Safo_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.09.020}} @article{Saghatelyan:2003, Abstract = {Over the past few decades, research exploring how the brain perceives, discriminates, and recognizes odorant molecules has received a growing interest. Today, olfaction is no longer considered a matter of poetry. Chemical senses entered the biological era when an increasing number of scientists started to elucidate the early stages of the olfactory pathway. A combination of genetic, biochemical, cellular, electrophysiological and behavioral methods has provided a picture of how odor information is processed in the olfactory system as it moves from the periphery to higher areas of the brain. Our group is exploring the physiology of the main olfactory bulb, the first processing relay in the mammalian brain. From different electrophysiological approaches, we are attempting to understand the cellular rules that contribute to the synaptic transmission and plasticity at this central relay. How olfactory sensory inputs, originating from the olfactory epithelium located in the nasal cavity, are encoded in the main olfactory bulb remains a crucial question for understanding odor processing. More importantly, the persistence of a high level of neurogenesis continuously supplying the adult olfactory bulb with newborn local neurons provides an attractive model to investigate how basic olfactory functions are maintained when a large proportion of local neurons are continuously renewed. For this purpose, we summarize the current ideas concerning the molecular mechanisms and organizational strategies used by the olfactory system to encode and process information in the main olfactory bulb. We discuss the degree of sensitivity of the bulbar neuronal network activity to the persistence of this high level of neurogenesis that is modulated by sensory experience. Finally, it is worth mentioning that analyzing the molecular mechanisms and organizational strategies used by the olfactory system to transduce, encode, and process odorant information in the olfactory bulb should aid in understanding the general neural mechanisms involved in both sensory perception and memory. Due to space constraints, this review focuses exclusively on the olfactory systems of vertebrates and primarily those of mammals. 0928-4257 Journal Article}, Author = {Saghatelyan, A. and Carleton, A. and Lagier, S. and de Chevigny, A. and Lledo, P. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {J Physiol Paris}, Keywords = {01 Adult neurogenesis general;A, I, M pdf}, Number = {4-6}, Organization = {Laboratory of Perception and Memory, Centre National de la Recherche Scientifique, Unite de Recherche Associee 2182, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris, France.}, Pages = {517-28}, Title = {Local neurons play key roles in the mammalian olfactory bulb}, Uuid = {DF85165C-DEAE-4FF8-9775-6950D0DA8F5F}, Volume = {97}, Year = {2003}, url = {papers/Saghatelyan_JPhysiolParis2003.pdf}} @article{Sahara:2001, Abstract = {The cellular localization of metabotropic glutamate receptors (mGluRs) (mGluR1alpha, 2/3, 5a and 7) in the main and accessory olfactory bulb (MOB and AOB) of adult rats was compared by using affinity purified polyclonal antibodies directed to their C-termini. mGluR1alpha and mGluR5a immunoreactivities were located in comparable structures of the MOB and AOB with different levels of intensity. mGluR5a reactivity was high in the AOB. mGluR2/3 showed a different pattern of expression in the MOB compared to that observed in the AOB; the periglomerular region of the MOB was strongly stained, but in the AOB it was the mitral/tufted cell layer that was intense. The mitral cell bodies in the MOB were strongly immunoreactive for mGluR7. These differences in the distribution of mGluRs in the MOB and AOB may reflect differences in synaptic transmission and sensitivity to neuromodulation in the two systems.}, Author = {Sahara, Y. and Kubota, T. and Ichikawa, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {Neurosci Lett}, Keywords = {I pdf;13 Olfactory bulb anatomy}, Number = {2}, Organization = {Department of Maxillofacial Biology, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, 113-8549, Tokyo, Japan}, Pages = {59-62.}, Title = {Cellular localization of metabotropic glutamate receptors mGluR1, 2/3, 5 and 7 in the main and accessory olfactory bulb of the rat}, Uuid = {86F7F8E8-181D-4C25-BA6C-6E94B0320216}, Volume = {312}, Year = {2001}, url = {papers/Sahara_NeurosciLett2001}} @article{Sahay:2007, Abstract = {The development of new treatments for depression is predicated upon identification of neural substrates and mechanisms that underlie its etiology and pathophysiology. The heterogeneity of depression indicates that its origin may lie in dysfunction of multiple brain regions. Here we evaluate adult hippocampal neurogenesis as a candidate mechanism for the etiology of depression and as a substrate for antidepressant action. Current evidence indicates that adult hippocampal neurogenesis may not be a major contributor to the development of depression, but may be required for some of the behavioral effects of antidepressants. We next revisit the functional differentiation of the hippocampus along the septo-temporal axis within the context of adult hippocampal neurogenesis and suggest that neurogenesis in the ventral dentate gyrus may be preferentially involved in regulation of emotion. Finally, we speculate on how increased adult hippocampal neurogenesis may modulate dentate gyrus function to confer the behavioral effects of antidepressants.}, Author = {Sahay, Amar and Hen, Rene}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {9809671}, Number = {9}, Organization = {Department of Neuroscience, Division of Integrative Neuroscience, Columbia University, 1051 Riverside Drive, Box 87, PI Annex, Room 767B, New York, New York 10032, USA. as2619\@columbia.edu}, Pages = {1110-5}, Pii = {nn1969}, Pubmed = {17726477}, Title = {Adult hippocampal neurogenesis in depression}, Uuid = {A8EAB088-BC16-46D4-9731-AA120262C797}, Volume = {10}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1969}} @article{Sailer:1997, Abstract = {Ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole) is a green fluorescent plant alkaloid that inhibits DNA topoisomerase II activity and possesses pharmacologic activity toward both murine and human leukemias in vivo. In this flow cytometric study, the uptake of ellipticine was monitored as a function of cell volume and cell cycle phase in viable human promyelocytic (HL-60) cells costained with the DNA fluorochrome Hoechst 33342. Uptake of ellipticine was time and dose dependent; however, drug content was quantitatively similar in all phases of the cell cycle when normalized for DNA content or similar to cell size when correlated with cell volume. The fluorescence lifetime values of ellipticine in HL-60 cells, as analyzed by novel flow cytometric analysis, reached a plateau when the intra-cellular ellipticine intensity was still rising with increasing drug concentration. Since the free drug and the different subcellular ellipticine complexes, including DNA and RNA, had different lifetime values, the changes in the lifetime values appear to reflect differing proportions of unbound drug to that bound to different cellular constituents in the cells. Further development of phase-sensitive flow cytometry will provide for multiple lifetime determinations so that quantitation of drugs bound to the different cellular components can be performed along with the simultaneous determination of total drug uptake and cell cycle position. Such analyses should provide useful information for the design of drugs with greater affinity for cytotoxic targets.}, Author = {Sailer, B. L. and Valdez, J. G. and Steinkamp, J. A. and Darzynkiewicz, Z. and Crissman, H. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0014-4827}, Journal = {Exp Cell Res}, Keywords = {Flow Cytometry;Cell Size;RNA, Neoplasm;Cell Compartmentation;Research Support, U.S. Gov't, P.H.S.;Time Factors;Dose-Response Relationship, Drug;Cell Survival;Fluorescent Dyes;Cell Cycle;Research Support, U.S. Gov't, Non-P.H.S.;HL-60 Cells;DNA, Neoplasm;Humans;Antineoplastic Agents;24 Pubmed search results 2008;Ellipticines}, Medline = {98005057}, Month = {10}, Nlm_Id = {0373226}, Number = {1}, Organization = {Life Sciences Division, Los Alamos National Laboratory, New Mexico 87545, USA.}, Pages = {259-67}, Pii = {S0014482797937174}, Pubmed = {9344606}, Title = {Monitoring uptake of ellipticine and its fluorescence lifetime in relation to the cell cycle phase by flow cytometry}, Uuid = {B61A9903-45D4-452D-85BF-FC084FD54C43}, Volume = {236}, Year = {1997}} @article{Saino-Saito:2007, Abstract = {The mechanisms underlying dopamine (DA) phenotypic differentiation in the olfactory bulb (OB) have not yet been fully elucidated and are the subject of some controversy. OB DA interneurons destined for the glomerular layer were shown to originate in the subventricular zone (SVZ) and in the rostral migratory stream (RMS). The current study investigated whether calcium/calmodulin-dependent protein kinase IV (CaMKIV) either alone or together with the Ets transcription factor ER81 was necessary for phenotypic determination during migration of progenitors. In most brain areas, including the OB, CaMKIV and ER81 displayed a reciprocal distribution. In the SVZ, only ER81 could be demonstrated. In the RMS, a subpopulation of progenitors contained ER81, but few, if any, contained CaMKIV. In OB, CaMKIV expression, restricted to deep granule cells, showed limited overlap with ER81. ER81 expression was weak in deep granule cells. Strong labeling occurred in the mitral and glomerular layers, where ER81 colabeled dopaminergic periglomerular cells that expressed either tyrosine hydroxylase (TH) or green fluorescent protein, the latter reporter gene under control of 9-kb of 5' TH promoter. Odor deprivation resulted in a significant 5.2-fold decline in TH immunoreactivity, but ER81 exhibited a relatively small 1.7-fold decline in immunoreactivity. TH expression as well as brain and bulb size were unchanged in CaMKIV knockout mice. These data suggest that ER81 may be required but is not sufficient for DA neuron differentiation and that CaMKIV is not directly involved in TH gene regulation. J. Comp. Neurol. 502:485-496, 2007. (c) 2007 Wiley-Liss, Inc.}, Author = {Saino-Saito, Sachiko and Cave, John W. and Akiba, Yosuke and Sasaki, Hayato and Goto, Kaoru and Kobayashi, Kazuto and Berlin, Roseann and Baker, Harriet}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {24 Pubmed search results 2008;13 Olfactory bulb anatomy}, Month = {6}, Nlm_Id = {0406041}, Number = {4}, Organization = {Department of Anatomy and Cell Biology, Yamagata University School of Medicine, Yamagata, Japan 990-9585.}, Pages = {485-96}, Pubmed = {17394138}, Title = {ER81 and CaMKIV identify anatomically and phenotypically defined subsets of mouse olfactory bulb interneurons}, Uuid = {A86B810F-5EB9-4C83-8927-5527B4C8C875}, Volume = {502}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21293}} @article{Sairanen:2005, Abstract = {Antidepressants increase proliferation of neuronal progenitor cells and expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. We investigated the role of BDNF signaling in antidepressant-induced neurogenesis by using transgenic mice with either reduced BDNF levels (BDNF+/-) or impaired trkB activation (trkB.T1-overexpressing mice). In both transgenic strains, chronic (21 d) imipramine treatment increased the number of bromodeoxyuridine (BrdU)-positive cells to degree similar to that seen in wild-type mice 24 h after BrdU administration, although the basal proliferation rate was increased in both transgenic strains. Three weeks after BrdU administration and the last antidepressant injection, the amount of newborn (BrdU- or TUC-4-positive) cells was significantly reduced in both BDNF+/- and trkB.T1-overexpressing mice, which suggests that normal BDNF signaling is required for the long-term survival of newborn hippocampal neurons. Moreover, the antidepressant-induced increase in the surviving BrdU-positive neurons seen in wild-type mice 3 weeks after treatment was essentially lost in mice with reduced BDNF signaling. Furthermore, we observed that chronic treatment with imipramine or fluoxetine produced a temporally similar increase in both BrdU-positive and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end-labeled neurons in the dentate gyrus, indicating that these drugs simultaneously increase both neurogenesis and neuronal elimination. These data suggest that antidepressants increase turnover of hippocampal neurons rather than neurogenesis per se and that BDNF signaling is required for the long-term survival of newborn neurons in mouse hippocampus.}, Author = {Sairanen, Mikko and Lucas, Guilherme and Ernfors, Patrik and Castr{\'e}n, Maija and Castr{\'e}n, Eero}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {04 Adult neurogenesis factors}, Month = {2}, Nlm_Id = {8102140}, Number = {5}, Organization = {Neuroscience Center, University of Helsinki, 00014 Helsinki, Finland.}, Pages = {1089-94}, Pii = {25/5/1089}, Pubmed = {15689544}, Title = {Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus}, Uuid = {EDFD38EC-D360-436D-9DE3-8C29EC397416}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3741-04.2005}} @article{Sakaguchi:2006, Abstract = {In the subventricular zone of the adult mammalian forebrain, neural stem cells (NSCs) reside and proliferate to generate young neurons. We screened factors that promoted the proliferation of NSCs in vitro by a recently developed proteomics technique, the ProteinChip system. In this screen, we identified a soluble carbohydrate-binding protein, Galectin-1, as a candidate. We show herein that Galectin-1 is expressed in a subset of slowly dividing subventricular zone astrocytes, which includes the NSCs. Based on results from intraventricular infusion experiments and phenotypic analyses of knockout mice, we demonstrate that Galectin-1 is an endogenous factor that promotes the proliferation of NSCs in the adult brain.}, Author = {Sakaguchi, Masanori and Shingo, Tetsuro and Shimazaki, Takuya and Okano, Hirotaka James and Shiwa, Mieko and Ishibashi, Satoru and Oguro, Hideyuki and Ninomiya, Mikiko and Kadoya, Toshihiko and Horie, Hidenori and Shibuya, Akira and Mizusawa, Hidehiro and Poirier, Fran\c{c}oise and Nakauchi, Hiromitsu and Sawamoto, Kazunobu and Okano, Hideyuki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {7505876}, Number = {18}, Organization = {Department of Physiology and Bridgestone Laboratory of Developmental and Regenerative Neurobiology, Keio University School of Medicine, Tokyo 160-8582, Japan.}, Pages = {7112-7}, Pii = {0508793103}, Pubmed = {16636291}, Title = {A carbohydrate-binding protein, Galectin-1, promotes proliferation of adult neural stem cells}, Uuid = {A1DA9C54-8B3E-4D72-A052-D2C03B503153}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0508793103}} @article{Sakakibara:2001, Abstract = {Musashi1 (Msi1) is a mammalian neural RNA-binding protein highly enriched in neural precursor cells that are capable of generating both neurons and glia during embryonic and postnatal CNS development. Here, we identified Musashi2 (Msi2), a novel mammalian RNA-binding protein that exhibits high sequence similarity to Msi1. The Msi2 transcript appeared to be distributed ubiquitously in a wide variety of tissues, consistent with the mRNA distribution of its Xenopus homolog, xrp1. However, the present study revealed cell type-specific and developmentally regulated expression of Msi2 in the mammalian CNS. Interestingly, Msi2 was expressed prominently in precursor cells in the ventricular zone and subventricular zone with the same pattern as Msi1 throughout CNS development. In the postnatal and adult CNS, this concurrent expression of Msi2 and Msi1 was seen in cells of the astrocyte lineage, including ependymal cells, a possible source for postnatal CNS stem cells. During neurogenesis, the expression of both Msi2 and Msi1 was lost in most postmitotic neurons, whereas Msi2 expression persisted in a subset of neuronal lineage cells, such as parvalbumin-containing GABA neurons in the neocortex and neurons in several nuclei of the basal ganglia. Msi2 may have a unique role that is required for the generation and/or maintenance of specific neuronal lineages. Furthermore, in vitro studies showed that Msi2 and Msi1 have similar RNA-binding specificity. These two RNA-binding proteins may exert common functions in neural precursor cells by regulating gene expression at the post-transcriptional level.}, Author = {Sakakibara, S. and Nakamura, Y. and Satoh, H. and Okano, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci}, Keywords = {Sequence Analysis, DNA;Protein Isoforms/genetics;In Situ Hybridization, Fluorescence;Cloning, Molecular;Neurons/cytology/*metabolism;*Gene Expression Regulation, Developmental;Animal;Physical Chromosome Mapping;02 Adult neurogenesis migration;RNA-Binding Proteins/genetics/*metabolism;Nerve Tissue Proteins/genetics;Mice, Inbred C57BL;BB abstr;03 Adult neurogenesis progenitor source;Stem Cells/cytology/*metabolism;Central Nervous System/cytology/*metabolism;Mice, Inbred ICR;Support, Non-U.S. Gov't;Organ Specificity;Mice;RNA, Messenger/metabolism;Molecular Sequence Data;Alternative Splicing/genetics;DNA, Complementary/genetics/isolation &purification}, Number = {20}, Organization = {Division of Neuroanatomy, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.}, Pages = {8091-107.}, Title = {Rna-binding protein Musashi2: developmentally regulated expression in neural precursor cells and subpopulations of neurons in mammalian CNS}, Uuid = {80F4582E-282C-4371-8C55-C1E0C69D964A}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11588182%20http://www.jneurosci.org/cgi/content/full/21/20/8091%20http://www.jneurosci.org/cgi/content/abstract/21/20/8091}} @article{Sakurada:1999, Abstract = {Adult rat-derived hippocampal progenitor cells express many of the molecules implicated in midbrain dopaminergic determination, including FGF receptors 1, 2 and 3, the sonic hedgehog receptor components Smo and Ptc, and the region-specific transcription factors Ptx3 and Nurr1. Here we use undifferentiated progenitors to probe the events leading to the dopaminergic phenotype and find that the influences of Nurr1 can be temporally and mechanistically uncoupled from the patterning influences of sonic hedgehog and FGF-8 or the more generic process of neuronal differentiation itself. In gain-of-function experiments, Nurr1 is able to activate transcription of the tyrosine hydroxylase gene by binding a response element within a region of the tyrosine hydroxylase promoter necessary for midbrain-specific expression. This activation is mediated through a retinoid X receptor independent mechanism and occurs in all precursors, regardless of differentiation status. Overexpression of Nurr1 does not affect proliferation or stimulate neuronal differentiation and has no influence on the expression of other dopaminergic markers. This uncoupling of tyrosine hydroxylase expression from other dopaminergic markers suggests that the midbrain dopaminergic identity is dictated by a combination of pan-dopaminergic (e.g., Shh/FGF-8) and region-specific (Nurr1) mechanisms.}, Author = {Sakurada, K. and Ohshima-Sakurada, M. and Palmer, T. D. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Development}, Keywords = {Binding Sites;Mesencephalon/metabolism;Nuclear Proteins/genetics/metabolism;C-Reactive Protein/genetics/metabolism;Stem Cells/*metabolism;Cells, Cultured;Age Factors;04 Adult neurogenesis factors;Receptors, Fibroblast Growth Factor/metabolism;Dopamine/metabolism;Transcription, Genetic/*physiology;Gene Expression Regulation, Developmental;Signal Transduction;Promoter Regions (Genetics);Cell Division;Nerve Tissue Proteins/genetics/metabolism;Neurons/*metabolism;Cell Differentiation/drug effects;Support, U.S. Gov't, P.H.S.;Animal;Fibroblast Growth Factor, Basic/metabolism/pharmacology;Tyrosine 3-Monooxygenase/genetics/*metabolism;Rats;Brain/cytology/*growth &development/metabolism;Transcription Factors/genetics/*metabolism;Proteins/metabolism;Support, Non-U.S. Gov't;C abstr;Amyloid P Component/genetics/metabolism;Hippocampus/cytology/growth &development/metabolism}, Number = {18}, Organization = {Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {4017-26.}, Title = {Nurr1, an orphan nuclear receptor, is a transcriptional activator of endogenous tyrosine hydroxylase in neural progenitor cells derived from the adult brain}, Uuid = {7DC093E4-CC01-4C63-AD8D-C18BF923B90F}, Volume = {126}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10457011%20http://www.biologists.com/Development/126/18/dev9664.html}} @article{Sakurai:2004, Abstract = {Current therapies for lysosomal storage diseases (LSDs), enzyme replacement therapy and bone marrow transplantation are effective for visceral organ pathology of LSD, but their effectiveness for brain involvement in LSDs is still a subject of controversy. As an alternative approach, we transplanted genetically modified bone marrow stromal (BMS) cells to lateral ventricle of newborn mucopolysaccharidosis VII (MPS VII) mice. MPS VII is one of LSDs and caused by deficiency of beta-glucuronidase (GUSB), resulting in accumulation of glycosaminoglycans (GAGs) in brain. At 2 weeks after transplantation, the GUSB enzyme-positive cells were identified in olfactory bulb, striatum and cerebral cortex, and the enzymatic activities in various brain areas increased. The GAGs contents in brain were reduced to near normal level at 4 weeks after transplantation. Although GUSB activity declined to homozygous level after 8 weeks, the reduction of GAGs persisted for 16 weeks. Microscopic examination indicated that the lysosomal distention was not found in treated animal brain. Cognitive function in MPS VII animals as evaluated by Morris Water Maze test in treated mice showed a marked improvement over nontreated animals. Brain transplantation of genetically modified BMS cells appears to be a promising approach to treat diffuse CNS involvement of LSDs.}, Author = {Sakurai, K. and Iizuka, S. and Shen, J-S S. and Meng, X-L L. and Mori, T. and Umezawa, A. and Ohashi, T. and Eto, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Transduction, Genetic;Behavior, Animal;Research Support, Non-U.S. Gov't;Mucopolysaccharidosis VII;Bone Marrow Cells;Retroviridae;Bone Marrow Transplantation;Gene Expression;Mice, Mutant Strains;Injections, Intraventricular;Gene Therapy;11 Glia;Glucuronidase;Brain;Mice;Animals;Genetic Vectors}, Month = {10}, Nlm_Id = {9421525}, Number = {19}, Organization = {Department of Gene Therapy, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.}, Pages = {1475-81}, Pii = {3302338}, Pubmed = {15295619}, Title = {Brain transplantation of genetically modified bone marrow stromal cells corrects CNS pathology and cognitive function in MPS VII mice}, Uuid = {005BBEB1-3E84-4B35-ACE7-C647C48E6B5A}, Volume = {11}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3302338}} @article{Sakurai:2001, Abstract = {The structurally related cell adhesion molecules L1 and Nr-CAM have overlapping expression patterns in cerebellar granule cells. Here we analyzed their involvement in granule cell development using mutant mice. Nr-CAM-deficient cerebellar granule cells failed to extend neurites in vitro on contactin, a known ligand for Nr-CAM expressed in the cerebellum, confirming that these mice are functionally null for Nr-CAM. In vivo, Nr-CAM-null cerebella did not exhibit obvious histological defects, although a mild size reduction of several lobes was observed, most notably lobes IV and V in the vermis. Mice deficient for both L1 and Nr-CAM exhibited severe cerebellar folial defects and a reduction in the thickness of the inner granule cell layer. Additionally, anti-L1 antibodies specifically disrupted survival and maintenance of Nr-CAM-deficient granule cells in cerebellar cultures treated with antibodies. The combined results indicate that Nr-CAM and L1 play a role in cerebellar granule cell development, and suggest that closely related molecules in the L1 family have overlapping functions.}, Author = {Sakurai, T. and Lustig, M. and Babiarz, J. and Furley, A. J. and Tait, S. and Brophy, P. J. and Brown, S. A. and Brown, L. Y. and Mason, C. A. and Grumet, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {Leukocyte L1 Antigen Complex;Purkinje Cells;Animals;Brain;Female;Neurites;Cell Adhesion Molecules, Neuronal;Male;Cerebellar Cortex;Research Support, U.S. Gov't, P.H.S.;Membrane Glycoproteins;Mice, Knockout;Protein-Tyrosine-Phosphatase;Mice;24 Pubmed search results 2008;Cell Adhesion Molecules;Nerve Tissue Proteins;Neural Cell Adhesion Molecules}, Medline = {21448627}, Month = {9}, Nlm_Id = {0375356}, Number = {6}, Organization = {W.M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.}, Pages = {1259-73}, Pii = {154/6/1259}, Pubmed = {11564762}, Title = {Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development}, Uuid = {2A9946AD-52AC-4ABA-9EB5-0CFD6F0EAA85}, Volume = {154}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200104122}} @article{Samanta:2007, Abstract = {Progenitor cells that express the transcription factor olig1 generate several neural cell types including oligodendrocytes and GABAergic interneurons in the dorsal cortex. The fate of these progenitor cells is regulated by a number of signals including bone morphogenetic proteins (BMPs) secreted in the dorsal forebrain. BMPs signal by binding to heteromeric serine-threonine kinase receptors formed by type I (BMPR1a, BMPR1b, Alk2) and type II (BMPRII) subunits. To determine the specific role of the BMPR1a subunit in lineage commitment by olig1-expressing cells, we used a cre/loxP genetic approach to ablate BMPR1a in these cells while leaving signaling from other subunits intact. There was a reduction in numbers of immature oligodendrocytes in the BMPR1a-null mutant brains at birth. However, by postnatal day 20, the BMPR1a-null mice had a significant increase in the number of mature and immature oligodendrocytes compared with wild-type littermates. There was also an increase in the proportion of calbindin-positive interneurons in the dorsomedial cortex of BMPR1a-null mice at birth without any change in the number of parvalbumin- or calretinin-positive cells. These effects were attributable, at least in part, to a decrease in the length of the cell cycle in subventricular zone progenitor cells. Thus, our findings indicate that BMPR1a mediates the suppressive effects of BMP signaling on oligodendrocyte lineage commitment and on the specification of calbindin-positive interneurons in the dorsomedial cortex.}, Author = {Samanta, Jayshree and Burke, Gordon M. and McGuire, Tammy and Pisarek, Anna J. and Mukhopadhyay, Abhishek and Mishina, Yuji and Kessler, John A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Aging;gamma-Aminobutyric Acid;Signal Transduction;Animals;Astrocytes;Aging;Cell Cycle;Basic Helix-Loop-Helix Transcription Factors;Oligodendroglia;Mutation;Cell Count;Bone Morphogenetic Proteins;Mice, Inbred C57BL;Calcium-Binding Protein, Vitamin D-Dependent;Bone Morphogenetic Protein Receptors, Type I;Smad Proteins;Animals, Newborn;Cell Lineage;Cerebral Cortex;Neurons;Mice;Interneurons;24 Pubmed search results 2008;Death;Stem Cells}, Month = {7}, Nlm_Id = {8102140}, Number = {28}, Organization = {Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.}, Pages = {7397-407}, Pii = {27/28/7397}, Pubmed = {17626200}, Title = {BMPR1a signaling determines numbers of oligodendrocytes and calbindin-expressing interneurons in the cortex}, Uuid = {67103AAA-9C19-402E-AA8E-A994A6E7AFB0}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1434-07.2007}} @article{Sanabria:2002, Abstract = {PURPOSE: Clinical, neuropathological, and electrophysiological data have shown that limbic structures are involved in the pathogenesis of temporal lobe epilepsy (TLE). In most cases, limbic-originated seizures frequently spread to extrahippocampal areas. It is unclear whether such distant circuitries, especially the neocortex, exhibit abnormal electrophysiology as consequences of a chronic epileptogenic process. The present research studied neuropathological abnormalities and in vitro electrophysiological properties of sensorimotor neocortex in pilocarpine-treated epileptic rats. METHODS: Adult epileptic animals showing six to seven seizures/week and saline-injected rats were selected for neurohistology. Coronal sections were sampled throughout the anteroposterior extent of the diencephalon and stained with cresyl violet (Nissl). Immunocytochemistry (ICC) was performed using anti-neurofilament (SMI-311) antibody. Extracellular (layer II/III) and intracellular (layer V) recordings were performed in coronal sensorimotor neocortical slices. Several electrophysiological aspects were examined such as evoked responses, intrinsic properties, and firing patterns of layer V pyramidal cells. RESULTS: Nissl staining showed a significant decrease of cortical thickness in epileptic rats when compared with controls, particularly in superficial layers (II-IV). Such abnormalities were also revealed by SMI-311 staining. SMI-311-labeled dendrite arborizations were more complex in layers I-II of epileptic rats. Epileptic rats manifested several abnormalities in extracellular field responses including hyperresponsiveness and presence of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-mediated polysynaptic activity. Although no significant changes were observed concerning passive intrinsic properties, it was possible to detect a higher proportion of bursting neurons distributed in layer V (60\%) of epileptic rats compared with 22\%in control slices. CONCLUSIONS: Taken together, our findings indicate damage, reorganization, and chronic hyperexcitability of sensorimotor neocortex in experimental TLE.}, Author = {Sanabria, Emilio R. Garrido and da Silva, Alexandre V. and Spreafico, Roberto and Cavalheiro, Esper A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Pilocarpine;Research Support, Non-U.S. Gov't;21 Neurophysiology;Epilepsy, Temporal Lobe;Immunohistochemistry;Neuronal Plasticity;Rats;Neocortex;Rats, Wistar;Electrophysiology;Male;Convulsants;Animals;24 Pubmed search results 2008;21 Epilepsy}, Medline = {22117259}, Nlm_Id = {2983306R}, Organization = {Laborat{\'o}rio de Neurologia Experimental, Universidade Federal de S\~{a}o Paulo-Escola Paulista de Medicina, Rua Botucatu 862, CEP 04023-900, S\~{a}o Paulo, SP, Brazil.}, Pages = {96-106}, Pii = {epis6030}, Pubmed = {12121302}, Title = {Damage, reorganization, and abnormal neocortical hyperexcitability in the pilocarpine model of temporal lobe epilepsy}, Uuid = {103BB3E2-0BC6-41F9-A06C-6901F38539E3}, Volume = {43 Suppl 5}, Year = {2002}} @article{Sanada:2005, Abstract = {Neurons in the developing mammalian brain are generated from progenitor cells in the proliferative ventricular zone, and control of progenitor division is essential to produce the correct number of neurons during neurogenesis. Here we establish that Gbetagamma subunits of heterotrimeric G proteins are required for proper mitotic-spindle orientation of neural progenitors in the developing neocortex. Interfering with Gbetagamma function in progenitors causes a shift in spindle orientation from apical-basal divisions to planar divisions. This results in hyperdifferentiation of progenitors into neurons as a consequence of both daughter cells adopting a neural fate instead of the normal asymmetric cell fates. Silencing AGS3, a nonreceptor activator of Gbetagamma, results in defects similar to the impairment of Gbetagamma, providing evidence that AGS3-Gbetagamma signaling in progenitors regulates apical-basal division and asymmetric cell-fate decisions. Furthermore, our observations indicate that the cell-fate decision of daughter cells is coupled to mitotic-spindle orientation in progenitors.}, Author = {Sanada, Kamon and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {10 Development;Cell Differentiation;Signal Transduction;Animals;Gene Expression Regulation;Carrier Proteins;Rats;GTP-Binding Protein beta Subunits;Mitotic Spindle Apparatus;GTP-Binding Protein gamma Subunits;Cell Polarity;RNA Interference;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Neurons;Gene Silencing;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Stem Cells;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {0413066}, Number = {1}, Organization = {Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.}, Pages = {119-31}, Pii = {S0092-8674(05)00454-X}, Pubmed = {16009138}, Title = {G protein betagamma subunits and AGS3 control spindle orientation and asymmetric cell fate of cerebral cortical progenitors}, Uuid = {45428CCD-AB5F-41A4-BA9C-8603576CE6BB}, Volume = {122}, Year = {2005}, url = {papers/Sanada_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.05.009}} @article{Sanada:2004, Abstract = {Disabled-1 regulates laminar organization in the developing mammalian brain. Although mutation of the disabled-1 gene in scrambler mice results in abnormalities in neuronal positioning, migratory behavior linked to Disabled-1 signaling is not completely understood. Here we show that newborn neurons in the scrambler cortex remain attached to the process of their parental radial glia during the entire course of radial migration, whereas wild-type neurons detach from the glial fiber in the later stage of migration. This abnormal neuronal-glial adhesion is highly linked to the positional abnormality of scrambler neurons and depends intrinsically on Disabled-1 Tyr220 and Tyr232, potential phosphorylation sites during corticogenesis. Importantly, phosphorylation at those sites regulates alpha3 integrin levels, which is critical for the timely detachment of migrating neurons from radial glia. Altogether, these results outline the molecular mechanism by which Disabled-1 signaling controls the adhesive property of neurons to radial glia, thereby maintaining proper neuronal positioning during corticogenesis.}, Author = {Sanada, Kamon and Gupta, Amitabh and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Animals;10 Development;Neuroglia;Cell Adhesion;Comparative Study;Nerve Tissue Proteins;Signal Transduction;Mice, Transgenic;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Cell Movement;Cerebral Cortex;Neurons;Mice}, Month = {4}, Nlm_Id = {8809320}, Number = {2}, Organization = {Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.}, Pages = {197-211}, Pii = {S0896627304002223}, Pubmed = {15091337}, Title = {Disabled-1-regulated adhesion of migrating neurons to radial glial fiber contributes to neuronal positioning during early corticogenesis}, Uuid = {0263B7B6-0BF9-4249-9D8B-E677CB0A8700}, Volume = {42}, Year = {2004}, url = {papers/Sanada_Neuron2004.pdf}} @article{Sanai:2004, Abstract = {The subventricular zone (SVZ) is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day. If the adult human brain contains a comparable germinal region, this could have considerable implications for future neuroregenerative therapy. Stem cells have been isolated from the human brain, but the identity, organization and function of adult neural stem cells in the human SVZ are unknown. Here we describe a ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain that proliferate in vivo and behave as multipotent progenitor cells in vitro. This astrocytic ribbon has not been observed in other vertebrates studied. Unexpectedly, we find no evidence of chains of migrating neuroblasts in the SVZ or in the pathway to the olfactory bulb. Our work identifies SVZ astrocytes as neural stem cells in a niche of unique organization in the adult human brain. 1476-4687 Journal Article}, Author = {Sanai, N. and Tramontin, A. D. and Quinones-Hinojosa, A. and Barbaro, N. M. and Gupta, N. and Kunwar, S. and Lawton, M. T. and McDermott, M. W. and Parsa, A. T. and Manuel-Garcia Verdugo, J. and Berger, M. S. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {Nature}, Keywords = {*Cell Movement;01 Adult neurogenesis general;Cell Differentiation;Brain/*cytology/ultrastructure;Adult;Human;Olfactory Bulb/cytology/ultrastructure;Cell Division;Autopsy;Support, U.S. Gov't, P.H.S.;Astrocytes/*cytology/ultrastructure;Multipotent Stem Cells/*cytology/ultrastructure;Cells, Cultured;Support, Non-U.S. Gov't;Neurons/*cytology/ultrastructure;A pdf;Biopsy}, Number = {6976}, Organization = {Department of Neurological Surgery and Brain Tumor Research Center, University of California San Francisco, San Francisco, California 94143, USA. nsanai\@itsa.ucsf.edu}, Pages = {740-4}, Title = {Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration}, Uuid = {4C112649-21D4-4EF7-A286-18BB953F54FF}, Volume = {427}, Year = {2004}, url = {papers/Sanai_Nature2004.pdf}} @article{Sanchez-Ramos:2000, Abstract = {Bone marrow stromal cells (BMSC) normally give rise to bone, cartilage, and mesenchymal cells. Recently, bone marrow cells have been shown to have the capacity to differentiate into myocytes, hepatocytes, and glial cells. We now demonstrate that human and mouse BMSC can be induced to differentiate into neural cells under experimental cell culture conditions. BMSC cultured in the presence of EGF or BDNF expressed the protein and mRNA for nestin, a marker of neural precursors. These cultures also expressed glial fibrillary acidic protein (GFAP) and neuron-specific nuclear protein (NeuN). When labeled human or mouse BMSC were cultured with rat fetal mesencephalic or striatal cells, a small proportion of BMSC-derived cells differentiated into neuron-like cells expressing NeuN and glial cells expressing GFAP. 0014-4886 Journal Article}, Author = {Sanchez-Ramos, J. and Song, S. and Cardozo-Pelaez, F. and Hazzi, C. and Stedeford, T. and Willing, A. and Freeman, T. B. and Saporta, S. and Janssen, W. and Patel, N. and Cooper, D. R. and Sanberg, P. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Exp Neurol}, Keywords = {*Interleukin-6;Human;RNA, Messenger/biosynthesis;Neurons/*cytology/metabolism;Corpus Striatum/cytology;Cells, Cultured;Animals;Rats;10 Development;Tretinoin/pharmacology;Rats, Sprague-Dawley;Mice, Transgenic;Mice, Inbred C57BL;Mesencephalon/cytology;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;Stromal Cells/*cytology/drug effects;Coculture;*Cell Differentiation/drug effects;Support, U.S. Gov't, Non-P.H.S.;Growth Inhibitors/pharmacology;Mice;Fibronectins/metabolism;Antigens, Differentiation/biosynthesis;Brain-Derived Neurotrophic Factor/pharmacology;Lymphokines/pharmacology;F;Bone Marrow Cells/*cytology/drug effects;Neuroglia/cytology/metabolism}, Number = {2}, Organization = {Department of Neurology, University of South Florida, Tampa, USA.}, Pages = {247-56}, Pubmed = {10915564}, Title = {Adult bone marrow stromal cells differentiate into neural cells in vitro}, Uuid = {BE67843C-33BC-4A77-BE3E-5840E160D7EA}, Volume = {164}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10915564}} @article{Sanchez-Vives:2000, Abstract = {The neocortex generates periods of recurrent activity, such as the slow (0.1-0.5 Hz) oscillation during slow-wave sleep. Here we demonstrate that slices of ferret neocortex maintained in vitro generate this slow (< 1 Hz) rhythm when placed in a bathing medium that mimics the extracellular ionic composition in situ. This slow oscillation seems to be initiated in layer 5 as an excitatory interaction between pyramidal neurons and propagates through the neocortex. Our results demonstrate that the cerebral cortex generates an 'up' or depolarized state through recurrent excitation that is regulated by inhibitory networks, thereby allowing local cortical circuits to enter into temporarily activated and self-maintained excitatory states. The spontaneous generation and failure of this self-excited state may account for the generation of a subset of cortical rhythms during sleep.}, Author = {Sanchez-Vives, M. V. and McCormick, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Electrophysiology;Animals;Synapses;Ferrets;research support, u.s. gov't, p.h.s. ;Culture Techniques;Epilepsy;Periodicity;Biological Clocks;Sleep;research support, non-u.s. gov't ;Nerve Net;Action Potentials;Cerebral Cortex;21 Neurophysiology;Neurons;Refractory Period, Electrophysiological;21 Cortical oscillations;24 Pubmed search results 2008;Cats}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {Section of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA. david.mccormick\@yale.edu}, Pages = {1027-34}, Pubmed = {11017176}, Title = {Cellular and network mechanisms of rhythmic recurrent activity in neocortex}, Uuid = {75638AB7-D62A-4092-9EFC-1539F1D8BEA3}, Volume = {3}, Year = {2000}, url = {papers/Sanchez-Vives_NatNeurosci2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/79848}} @article{Sancini:2001, Abstract = {Knockout Otx1 mice present a microcephalic phenotype mainly due to reduced deep neocortical layers and spontaneous recurrent seizures. We investigated the excitable properties of layer V pyramidal neurons in neocortical slices prepared from Otx1-/- mice and age-matched controls. The qualitative firing properties of the neurons of Otx1-/- mice were identical to those found in wild-type controls, but the proportion of intrinsically bursting (IB) neurons was significantly smaller. This is in line with the lack of the Otx1 gene contribution to the generation and differentiation of neurons destined for the deep neocortical layers, in which IB neurons are located selectively in wild-type rodents. The pyramidal neurons recorded in Otx1-/- mice responded to near-threshold electrical stimulation of the underlying white matter, with aberrant polysynaptic excitatory potentials often leading to late action potential generation. When the strength of the stimulus was increased, the great majority of the Otx1-/- neurons (78\%) responded with a prominent biphasic inhibitory postsynaptic potential that was significantly larger than that observed in the wild-type mice, and was often followed by complex postinhibitory depolarizing events. Both late excitatory postsynaptic potentials and postinhibitory excitation were selectively suppressed by NMDA receptor antagonists, but not by AMPA antagonists. We conclude that the cortical abnormalities of Otx1-/- neocortex due to a selective loss of large projecting neurons lead to a complex rearrangement of local circuitry, which is characterized by an excess of N-methyl-d-aspartate-mediated polysynaptic excitation that is counteracted by GABA-mediated inhibition in only a limited range of stimulus intensity. Prominent postsynaptic inhibitory potentials may also act as a further pro-epileptogenic event by synchronizing abnormal excitatory potentials.}, Author = {Sancini, G. and Franceschetti, S. and Lavazza, T. and Panzica, F. and Cipelletti, B. and Frassoni, C. and Spreafico, R. and Acampora, D. and Avanzini, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {gamma-Aminobutyric Acid;Excitatory Amino Acid Antagonists;Transcription Factors;Electric Stimulation;Animals;Gene Expression Regulation, Developmental;Rats;Otx Transcription Factors;Synaptic Transmission;21 Epilepsy;Homeodomain Proteins;Epilepsy;2-Amino-5-phosphonovalerate;Pyramidal Cells;Receptors, AMPA;Action Potentials;Nervous System Malformations;Mice, Knockout;21 Neurophysiology;Cerebral Cortex;Cell Size;Mice;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Nerve Tissue Proteins;Neural Inhibition;Research Support, Non-U.S. Gov't}, Medline = {21541151}, Month = {10}, Nlm_Id = {8918110}, Number = {7}, Organization = {Istituto Nazionale Neurologico C. Besta, Via Celoria 11, 20133 Milan, Italy.}, Pages = {1065-74}, Pii = {1723}, Pubmed = {11683898}, Title = {Potentially epileptogenic dysfunction of cortical NMDA- and GABA-mediated neurotransmission in Otx1-/- mice}, Uuid = {3B0C8880-E17F-496F-9E3C-E1ABDE17F769}, Volume = {14}, Year = {2001}} @article{Sanes:1989, Abstract = {Analysis of neural cell lineage in vertebrates has been limited by a lack of methods for introducing stable tracers into individual cells at relatively late stages of development. Recent progress in the design of recombinant retroviral vectors provides a novel approach to this problem. When a retrovirus infects a dividing cell, its genome integrates into a chromosome of the infected cell and is inherited by that cell's progeny. For lineage tracing, viral structural genes are replaced by a bacterial beta-galactosidase gene; infected cells are therefore unable to produce new virions, but can produce galactosidase, which is detectable histochemically. By infecting cells and identifying their progeny at appropriate stages, it has been possible to obtain new data on cell lineage in retina, cerebral cortex, optic tectum, and peripheral nerve.}, Author = {Sanes, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Retroviridae;Cell Division;Histocytochemistry;Nervous System;Animals;15 Retrovirus mechanism;Galactosidases;review}, Medline = {89267944}, Month = {1}, Nlm_Id = {7808616}, Number = {1}, Pages = {21-8}, Pubmed = {2471334}, Title = {Analysing cell lineage with a recombinant retrovirus}, Uuid = {FBEC10D5-D067-11DA-8A8C-000D9346EC2A}, Volume = {12}, Year = {1989}} @article{Santos:2000, Abstract = {PURPOSE: Animal models are useful for the study of status epilepticus (SE)-induced epileptogenesis and neurological sequelae, especially during early brain development. Here, we show several permanent abnormalities in animals subjected to multiple SE during early development. METHODS: Wistar pup rats (7 to 9 days old) were subjected to three consecutive episodes of SE induced by systemic pilocarpine injections. To study the long-lasting consequences of early-induced SE. chronic electroencephalographic recordings were made from the hippocampus and cortex and several behavioral tests (inhibitory step-down avoidance, rota-rod, open field, elevated plus-maze, and Skinner box) were performed at postnatal days 30 to 90. We also investigated in vitro electrophysiological responses of the CA1 area using extracellular recordings in hippocampal slices. A histological analysis was done using cresyl violet staining 24 hours and several months after SE induction. Apoptotic cell death was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL staining) 24 hours after the last SE episode. RESULTS: Electroencephalographic recordings from 30- to 90-day-old rats that had been subjected to multiple SE episodes in early life showed marked changes compared with those from nontreated controls. These included frequent episodes of continuous complex spiking activity and high-voltage ictal discharges, with a small percentage of these rats presenting spontaneous behavioral seizures. These animals also presented evidence of severe cognitive deficit in adulthood. In vitro, a persistent hyperexcitability of the CA1 area was detected in experimental animals. Histological analysis of the brains did not reveal any major long-term pathological changes. Nevertheless, an increased number of TUNEL-positive nuclei were present in some animals in both the hippocampus and the thalamus. CONCLUSIONS: These data show persistent abnormalities in animals subjected to multiple SE episodes during early postnatal development. SE may result in important plastic changes in critical periods of brain maturation leading to long-lasting epileptogenesis, as manifested by electrographic epileptiform discharges, behavioral deficits, and in vitro hyperexcitability of hippocampal networks.}, Author = {Santos, N. F. and Marques, R. H. and Correia, L. and Sinigaglia-Coimbra, R. and Calderazzo, L. and Sanabria, E. R. and Cavalheiro, E. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Pilocarpine;Animals;Rats;Neuronal Plasticity;Brain;Apoptosis;21 Epilepsy;Hippocampus;Rats, Wistar;Disease Models, Animal;Behavior, Animal;Male;Status Epilepticus;In Situ Nick-End Labeling;Cerebral Cortex;21 Neurophysiology;Age Factors;24 Pubmed search results 2008;Electroencephalography;Research Support, Non-U.S. Gov't}, Medline = {20452150}, Nlm_Id = {2983306R}, Organization = {Laborat{\'o}rio de Neurologia Experimental, Universidade Federal de S\~{a}o Paulo-Escola Paulista de Medicina, Brazil.}, Pages = {S57-63}, Pubmed = {10999521}, Title = {Multiple pilocarpine-induced status epilepticus in developing rats: a long-term behavioral and electrophysiological study}, Uuid = {2954266D-BC5E-45B3-B04C-1A1AFE25DEEB}, Volume = {41 Suppl 6}, Year = {2000}} @article{Santra:2006, Abstract = {Doublecortin (DCX) is one of the three genes found from Affymetrix gene chip analysis related to glioma patient survival. Two other genes (e.g., osteonectin and semaphorin 3B) are well characterized as antioncogenic and tumor suppressor genes. However, there is no report about the involvement of DCX in cancer. Here, we show that gene transfer technology into DCX-deficient glioblastoma cell lines, such as A172, U87, U251N, RG2, and 9L, with DCX cDNA significantly suppressed growth of these glioma cells. U87 cells with ectopic expression of DCX exhibit a marked suppression of the transformed phenotype as growth arrested in the G(2) phase of the cell cycle progression, small colony formation in soft agar, and no tumor formation in nude rats. This transformed phenotype can be restored by knocking down DCX expression with DCX small interfering RNA. DCX was highly phosphorylated in glioma cells. Phosphorylation in the glioma cells was greater than in noncancer cells such as mouse NIH 3T3 and human embryonic kidney 293T cells. Coimmunoprecipitation of the phosphorylated DCX and spinophilin/neurabin II from DCX-synthesizing glioma cells indicated their interaction. This interaction would lead to a block of anchorage-independent growth as neurabin II is a synergistic inhibitor of anchorage-independent growth with p14ARF (ARF). Interaction between phosphorylated DCX and neurabin II may induce the association of the protein phosphatase 1 catalytic subunit (PP1) with neurabin II and inactivate PP1 and block mitosis during G(2) and M phases of the cell cycle progression. Thus, DCX seems to be a tumor suppressor of glioma.}, Author = {Santra, Manoranjan and Zhang, Xuepeng and Santra, Sutapa and Jiang, Feng and Chopp, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0008-5472}, Journal = {Cancer Res}, Keywords = {Gene Expression Regulation, Neoplastic;Microtubule-Associated Proteins;Animals;Humans;Rats;Phosphorylation;Cell Cycle;Mitosis;Lentivirus;Cell Line, Tumor;RNA, Messenger;Brain Neoplasms;RNA, Small Interfering;Genetic Vectors;Neuropeptides;Glioblastoma;3T3 Cells;research support, n.i.h., extramural;Mice;Protein Biosynthesis;22 Stem cells;24 Pubmed search results 2008;Survival;22 Cancer;Transcription, Genetic}, Month = {12}, Nlm_Id = {2984705R}, Number = {24}, Organization = {Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.}, Pages = {11726-35}, Pii = {66/24/11726}, Pubmed = {17178868}, Title = {Ectopic doublecortin gene expression suppresses the malignant phenotype in glioblastoma cells}, Uuid = {0A37EB51-63A7-4A00-80A9-2FAC77FA88C6}, Volume = {66}, Year = {2006}, url = {papers/Santra_CancerRes2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1158/0008-5472.CAN-06-1978}} @article{Sapir:2008, Abstract = {Membrane fusion is a fundamental requirement in numerous developmental, physiological, and pathological processes in eukaryotes. So far, only a limited number of viral and cellular fusogens, proteins that fuse membranes, have been isolated and characterized. Despite the diversity in structures and functions of known fusogens, some common principles of action apply to all fusion reactions. These can serve as guidelines in the search for new fusogens, and may allow the formulation of a cross-species, unified theory to explain divergent and convergent evolutionary principles of membrane fusion.}, Author = {Sapir, Amir and Avinoam, Ori and Podbilewicz, Benjamin and Chernomordik, Leonid V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1534-5807}, Journal = {Dev Cell}, Keywords = {15 ERVs retroelements;research support, non-u.s. gov't;08 Aberrant cell cycle;research support, n.i.h., intramural;15 Retrovirus mechanism;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {101120028}, Number = {1}, Organization = {Department of Biology, The Technion, Israel Institute of Technology, Haifa 32000, Israel.}, Pages = {11-21}, Pii = {S1534-5807(07)00485-6}, Pubmed = {18194649}, Title = {Viral and developmental cell fusion mechanisms: conservation and divergence}, Uuid = {FCA61FE0-0367-4B8A-90E0-87CC19150FCF}, Volume = {14}, Year = {2008}, url = {papers/Sapir_DevCell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devcel.2007.12.008}} @article{Saradzhishvili:1971, Author = {Saradzhishvili, P. M. and Tokhadze, G. A. and Baratashvili, N. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0023-2149}, Journal = {Klin Med (Mosk)}, Keywords = {Epilepsy;Electroencephalography;Muscles;21 Neurophysiology;Female;Muscle Tonus;Electromyography;Electrophysiology;Male;Humans;Cerebral Cortex;21 Epilepsy;24 Pubmed search results 2008}, Medline = {71260076}, Month = {4}, Nlm_Id = {2985204R}, Number = {4}, Pages = {22-9}, Pubmed = {5561602}, Title = {[Basic electrophysiologic characteristics of muscle tone disorders during convulsive and nonconvulsive forms of epilepsy]}, Uuid = {2B16A989-7A64-4257-AAF6-6A0EC264549B}, Volume = {49}, Year = {1971}} @article{Sarkisian:2001, Abstract = {One approach to defining mechanisms essential to neocortical development is to analyze the phenotype of novel spontaneous mutations that dramatically affect the generation and differentiation of different neocortical neurons. Previously we have shown that there is a large decrease in the total number of cortical neurons in the flathead mutant rat, and in this paper we show that the flathead (fh/fh) mutation causes an even larger decrease in the number of interneurons. The decrease in relative interneuron number is different in different cortical lamina and for different interneuron subtypes. Specifically, the percentage of GABA and calretinin- positive cells in upper layers of somatosensory cortex is not appreciably decreased in homozygous mutants, while other interneuron subtypes in somatosensory cortex and all GABA-positive interneuron types in entorhinal cortex are decreased. In addition, the soma and dendritic arbors of interneurons in flathead are greatly hypertrophied, while those of pyramidal neurons are not. Furthermore, we found that at embryonic day 14, flathead mutants display high levels of cell death throughout both the neocortical and ganglionic eminence (GE) proliferative zones with a larger increase in cell death in the GE than in the neocortical VZ. In addition, we provide evidence that there is widespread cytokinesis failure resulting in binucleate pyramidal cells and interneurons, and the number of binucleate interneurons is greater than the number of binucleate pyramidal neurons. Together, these results demonstrate that the fh mutation causes dramatic alterations in interneuron development, and suggest that the flathead mutation causes differential cytokinesis failure and cell death in different types of neocortical progenitors. 21352665 1047-3211 Journal Article}, Author = {Sarkisian, M. R. and Frenkel, M. and Li, W. and Oborski, J. A. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {Cereb Cortex}, Keywords = {Pyramidal Cells/physiology/ultrastructure;Rats;Cell Cycle/physiology;Cell Death/physiology;Mutation/genetics/*physiology;Cell Size/genetics;Cell Count;Animal;Rats, Inbred Strains;Rats, Wistar;Male;Reverse Transcriptase Polymerase Chain Reaction;CK;Cerebral Cortex/cytology/*growth &development/ultrastructure;Support, Non-U.S. Gov't;Interneurons/*physiology/ultrastructure;Animals, Newborn;Genotype;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Mitosis/genetics}, Number = {8}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA.}, Pages = {734-43}, Title = {Altered interneuron development in the cerebral cortex of the flathead mutant}, Uuid = {AA7B0A5A-69E9-11DA-A4B6-000D9346EC2A}, Volume = {11}, Year = {2001}, url = {papers/Sarkisian_CerebCortex2001.pdf}} @article{Sarkisian:1999a, Abstract = {PURPOSE: Disorders in normal central nervous system (CNS) development are often associated with epilepsy. This report characterizes seizures in a novel genetic model of developmental epilepsy, the Flathead (FH) rat. METHODS: Animals (n = 76) ages P0-22 were monitored for clinical and electrographic seizure activity. The effects of various AEDs on seizure frequency and duration also were assessed: phenobarbital (PB; 40 mg/kg), valproate (VPA; 400 mg/kg), or ethosuximide (ESM; 600 mg/kg). RESULTS: FHs display episodes of behavior characterized by whole-body tremor, strub tail, alternating forelimb clonus, and complete tonus. EEG recordings from neocortex reveal that FH seizures are bilateral and begin around P7. Seizures occur at a frequency of approximately six per hour from P7 to P18 and the average duration of seizures increases through development. PB, VPA, and ESM failed to prevent seizures; however, PB significantly increased the interval of seizures but had no effects on the duration of seizures, whereas VPA decreased the duration of seizures and not the interval. CONCLUSIONS: Seizures in FH rats occur at a constant and high frequency through a defined period in early postnatal development, and these seizures are not completely blocked by high doses of PB, VPA, or ESM. Because FH is a single-locus mutant displaying a highly regular pattern of seizure activity, it is an ideal model for examining the process of epileptogenesis in the developing brain, evaluating new AED therapies, and determining the identity of a gene essential to the normal development of cortical excitability.}, Author = {Sarkisian, M.R. and Rattan, S. and D'Mello, S.R. and LoTurco, J.J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Journal = {Epilepsia}, Keywords = {CK}, Pages = {394-400}, Title = {Characterization of seizures in the flathead rat: a new genetic model of epilepsy in early postnatal development}, Uuid = {D7AD22C8-69B0-11DA-A4B6-000D9346EC2A}, Volume = {40}, Year = {1999}} @article{Sarkisian:1999, Abstract = {PURPOSE: Disorders in normal central nervous system (CNS) development are often associated with epilepsy. This report characterizes seizures in a novel genetic model of developmental epilepsy, the Flathead (FH) rat. METHODS: Animals (n = 76) ages P0-22 were monitored for clinical and electrographic seizure activity. The effects of various AEDs on seizure frequency and duration also were assessed: phenobarbital (PB; 40 mg/kg), valproate (VPA; 400 mg/kg), or ethosuximide (ESM; 600 mg/kg). RESULTS: FHs display episodes of behavior characterized by whole-body tremor, strub tail, alternating forelimb clonus, and complete tonus. EEG recordings from neocortex reveal that FH seizures are bilateral and begin around P7. Seizures occur at a frequency of approximately six per hour from P7 to P18 and the average duration of seizures increases through development. PB, VPA, and ESM failed to prevent seizures; however, PB significantly increased the interval of seizures but had no effects on the duration of seizures, whereas VPA decreased the duration of seizures and not the interval. CONCLUSIONS: Seizures in FH rats occur at a constant and high frequency through a defined period in early postnatal development, and these seizures are not completely blocked by high doses of PB, VPA, or ESM. Because FH is a single-locus mutant displaying a highly regular pattern of seizure activity, it is an ideal model for examining the process of epileptogenesis in the developing brain, evaluating new AED therapies, and determining the identity of a gene essential to the normal development of cortical excitability.}, Author = {Sarkisian, M. R. and Rattan, S. and D'Mello, S. R. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Rats, Mutant Strains;Animals;Rats;Seizures;Phenobarbital;Brain;Valproic Acid;Female;Epilepsy;Mutation;21 Dysplasia-heterotopia;Rats, Wistar;research support, non-u.s. gov't;Behavior, Animal;Models, Genetic;Disease Models, Animal;Ethosuximide;Male;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Cerebral Cortex;24 Pubmed search results 2008;Electroencephalography;Anticonvulsants}, Month = {4}, Nlm_Id = {2983306R}, Number = {4}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269, USA.}, Pages = {394-400}, Pubmed = {10219263}, Title = {Characterization of seizures in the flathead rat: a new genetic model of epilepsy in early postnatal development}, Uuid = {E06D81CF-2705-4AF9-BFF9-B626418A72E8}, Volume = {40}, Year = {1999}} @article{Sarkisian:2002, Author = {Sarkisian, M. R. and Li, W. and Di Cunto, F. and D'Mello, S. R. and LoTurco, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Journal = {J Neurosci}, Keywords = {Central Nervous System/abnormalities/cytology/embryology;Rats;Neurons/*cytology;Phenotype;Animal;Exons/genetics;CK;Stem Cells/cytology/*metabolism;Protein-Serine-Threonine Kinases/*deficiency/genetics/metabolism;Support, Non-U.S. Gov't;Blotting, Western;Organ Specificity;Nervous System Malformations/*enzymology/genetics;rhoA GTP-Binding Protein/metabolism;Support, U.S. Gov't, P.H.S.;Phosphotransferases/deficiency/genetics/metabolism;DNA Mutational Analysis;Cell Division/*physiology;Immunohistochemistry;Rats, Mutant Strains}, Number = {8}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269, USA.}, Pages = {RC217}, Title = {Citron-kinase, a protein essential to cytokinesis in neuronal progenitors, is deleted in the flathead mutant rat}, Uuid = {F60F3812-69B0-11DA-A4B6-000D9346EC2A}, Volume = {22}, Year = {2002}, url = {papers/Sarkisian_JNeurosci2002.pdf}} @article{Sarkisian:2006, Abstract = {Periventricular heterotopia (PVH) is a congenital malformation of human cerebral cortex frequently associated with Filamin-A (FLN-A) mutations but the pathogenetic mechanisms remain unclear. Here, we show that the MEKK4 (MAP3K4) pathway is involved in Fln-A regulation and PVH formation. MEKK4(-/-) mice developed PVH associated with breaches in the neuroependymal lining which were largely comprised of neurons that failed to reach the cortical plate. RNA interference (RNAi) targeting MEKK4 also impaired neuronal migration. Expression of Fln was elevated in MEKK4(-/-) forebrain, most notably near sites of failed neuronal migration. Importantly, recombinant MKK4 protein precipitated a complex containing MEKK4 and Fln-A, and MKK4 mediated signaling between MEKK4 and Fln-A, suggesting that MKK4 may bridge these molecules during development. Finally, we showed that wild-type FLN-A overexpression inhibited neuronal migration. Collectively, our results demonstrate a link between MEKK4 and Fln-A that impacts neuronal migration initiation and provides insight into the pathogenesis of human PVH.}, Author = {Sarkisian, Matthew R. and Bartley, Christopher M. and Chi, Hongbo and Nakamura, Fumihiko and Hashimoto-Torii, Kazue and Torii, Masaaki and Flavell, Richard A. and Rakic, Pasko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:56 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8809320}, Number = {5}, Organization = {Department of Neurobiology and Kavli Institute of Neuroscience, Yale University School of Medicine, New Haven, Connecticut 06520, USA.}, Pages = {789-801}, Pii = {S0896-6273(06)00823-3}, Pubmed = {17145501}, Title = {MEKK4 signaling regulates filamin expression and neuronal migration}, Uuid = {05E99490-3D5C-48ED-BA8A-42754CE3BB29}, Volume = {52}, Year = {2006}, url = {papers/Sarkisian_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.10.024}} @article{Sasaki:1989, Abstract = {We isolated two subclasses of astrocytes, oligodendrocytes and ameboid microglia from Lewis rat cerebral cortex and analyzed Ia antigen expression on each glial cell type by immunofluorescent microscopy and cytofluorometry. All of these expressed little or no Ia without interferon-gamma (IFN-gamma) treatment. Following IFN-gamma treatment, Ia expression was observed on a majority (approximately 80\%) of ameboid microglia, on half (approximately 55\%) of the type 1 astrocytes, on a small number (approximately 7\%) of type 2 astrocytes, but not on oligodendrocytes. These findings suggest that the type 1 astrocyte and microglia may play more predominant roles in Ia-related, immune-mediated intracerebral lesions although the type 2 astrocytes may also be involved. 90062513 0165-5728 Journal Article}, Author = {Sasaki, A. and Levison, S. W. and Ting, J. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neuroimmunol}, Keywords = {Histocompatibility Antigens Class II/*immunology;Flow Cytometry;Rats, Inbred Lew;G abstr;Rats;Comparative Study;Oligodendroglia/immunology;Animal;11 Glia;Cerebral Cortex/cytology/*immunology;Microscopy, Fluorescence;Neuroglia/*immunology/ultrastructure;Cells, Cultured;Support, Non-U.S. Gov't;Astrocytes/immunology}, Number = {1}, Organization = {Lineberger Cancer Center, University of North Carolina, Chapel Hill 27599.}, Pages = {63-74}, Pubmed = {2584392}, Title = {Comparison and quantitation of Ia antigen expression on cultured macroglia and ameboid microglia from Lewis rat cerebral cortex: analyses and implications}, Uuid = {0D6CABE3-3E12-4B35-BBE1-93D0FE585CE9}, Volume = {25}, Year = {1989}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2584392}} @article{Sasaki:1990, Abstract = {The roles of intracellular second messengers in interferon-gamma (IFN-gamma)-induced Ia antigen (Ag) expression by astroglia and microglia were examined. Ia Ag on both glia types was induced by IFN-gamma. Reagents known to increase intracellular cAMP or activate intracellular protein kinase C (PKC) reduced IFN-gamma-induced Ia Ag expression by astroglia. In contrast, increasing intracellular cAMP had no suppressive effect on Ia Ag expression by microglia. These results indicate (1) cAMP and PKC negatively regulate IFN-gamma-induced Ia expression on astroglia, and (2) Ia expression is regulated differentially in astroglia vs. microglia. These findings may explain the frequent observation of Ia+ microglia (or macrophages) but not astroglia in various neurodegenerative diseases. 91009783 0165-5728 Journal Article}, Author = {Sasaki, A. and Levison, S. W. and Ting, J. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neuroimmunol}, Keywords = {Neuroglia/*immunology;Enzyme Activation;Second Messenger Systems/*physiology;Protein Kinase C/*physiology;G abstr;Rats;Tetradecanoylphorbol Acetate/pharmacology;Animal;11 Glia;Histocompatibility Antigens Class II/*analysis;Cells, Cultured;Support, Non-U.S. Gov't;Rats, Inbred Strains;Interferon Type II/*pharmacology;Cyclic AMP/*physiology}, Number = {1-3}, Organization = {Lineberger Cancer Center, University of North Carolina, Chapel Hill 27599.}, Pages = {213-22}, Pubmed = {2170439}, Title = {Differential suppression of interferon-gamma-induced Ia antigen expression on cultured rat astroglia and microglia by second messengers}, Uuid = {8EDC6C49-6025-410C-9192-A2141BB9C8BC}, Volume = {29}, Year = {1990}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2170439}} @article{Sasaki:2007, Abstract = {The brain is spontaneously active even in the absence of external input. This ongoing background activity impacts neural information processing. We used functional multineuron calcium imaging (fMCI) to analyze the net structure of spontaneous CA3 network activity in hippocampal slice cultures loaded with Oregon Green 488 BAPTA-1 using a spinning disk confocal microscope (10-30 frames/s). Principal component analysis revealed that network states, defined by active cell ensembles, were stable but heterogenous and discrete. These states were stabilized through synaptic activity and maintained against external perturbations. A few discrete states emerged during our observation period of up to 30 min. Networks tended to stay in a single state for tens of seconds and then suddenly jump to a new state. After a state transition, the old state was rarely, if ever, revisited by the network during our observation period. This temporal profile of state transitions could not be simulated by a hidden Markov model, indicating that the state dynamics is nonrandomly organized. Within each state, the pattern of network activity tended to stabilize in a specific configuration. Neither maintenance nor transition of the network states required NMDA receptor activity. These findings suggest that the network states are metastable, rather than multistable, and might be governed by local attractor-like dynamics. The fMCI data analyzed here are available at http://hippocampus.jp/data/}, Author = {Sasaki, Takuya and Matsuki, Norio and Ikegaya, Yuji}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;Action Potentials;Hippocampus;Rats;21 Calcium imaging;Calcium;Rats, Wistar;comparative study;Nerve Net;Animals;Cells, Cultured;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8102140}, Number = {3}, Organization = {Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo 113-0033, Japan.}, Pages = {517-28}, Pii = {27/3/517}, Pubmed = {17234584}, Title = {Metastability of active CA3 networks}, Uuid = {0DB8EE44-F8FC-427F-8B70-4F4D34EFFFBD}, Volume = {27}, Year = {2007}, url = {papers/Sasaki_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4514-06.2007}} @article{Sasaki:1996, Abstract = {The immunophenotype of perivascular cells (PC) in temporal lobe tissues obtained at autopsy in 48 patients (aged 41-88 years) was characterized using light and electron microscopic immunocytochemistry with a variety of antibodies. In all cases studied, PC bearing CD11c (Ki-M1P) and CD68 (KP1) were distributed throughout the temporal cortex. In addition to Ki-M1P and KP1, the monoclonal antibodies against major histocompatibility complex (MHC) class II antigen (Ag) (LN-3, CR3.43), anti-leucocyte common antigen (LCA), LN-5, Mac 387 were all found in PC with variable immunoreactivity. In contrast, LN-1 and OPD4 were not found in PC, although the former showed nearly constant staining of resting microglia. Semiquantitative analysis disclosed differences in the numbers of cells labeled with the markers in the 21 normal brains (Ki-M1P >KP1 >>LCA, LN-3, LN-5 >>Mac 387). Ultrastructurally, immunoreactivity for Ki-M1P, KP1, and LN-3 was observed in PC with cytoplasm containing dense lysosomal bodies. In brains from patients with Alzheimer's type dementia, PC were seen in the wall of beta-amyloid protein-positive small vessels. However, there was no definite alteration of antigenicity in PC from AD brains compared with those from normal brains. The immunophenotype of PC was similar to that of macrophages, which were observed in the perivascular spaces and the leptomeninges in some normal and diseased brains. In contrast with PC, however, macrophages showed high incidence of labeling for some macrophage markers LN-5 and Mac 387. These findings demonstrate that PC may be a normal constituent of the adult human brain with a variable expression of monocyte/macrophages markers and MHC class II Ag and that PC could be distinguished from resting microglia by their morphology and by their immunophenotype.}, Author = {Sasaki, A. and Nakazato, Y. and Ogawa, A. and Sugihara, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {1320-5463}, Journal = {Pathol Int}, Keywords = {Humans;Amyloid beta-Protein;Middle Aged;Pericytes;Macrophages;Immunoenzyme Techniques;Female;Antigens, CD;Cell Count;11 Glia;Immunophenotyping;Male;Aged;Alzheimer Disease;Aged, 80 and over;Adult;Temporal Lobe;Biological Markers;Histocompatibility Antigens Class II;Blood Vessels}, Medline = {20305900}, Month = {1}, Nlm_Id = {9431380}, Number = {1}, Organization = {Department of Pathology, Gunma University School of Medicine, Maebashi, Japan.}, Pages = {15-23}, Pubmed = {10846545}, Title = {The immunophenotype of perivascular cells in the human brain}, Uuid = {30B580C2-62A5-4E51-A897-C0011E046F8E}, Volume = {46}, Year = {1996}} @article{Sato:2007a, Abstract = {Wiskott-Aldrich syndrome protein (WASP) plays important roles in TCR signaling, but its roles in signal transduction in innate immune cells have not been well characterized. As microglia are the primary immune effector cells in the brain, WASP may possibly have important roles in microglial activation, such as production of inflammatory and anti-inflammatory cytokines and neurotoxic factors. Here, we established a microglial cell line from WASP dominant-negative transgenic (Tg) mice overexpressing the N-terminal enabled/vasodilator-stimulated phosphoprotein homology 1 (EVH1) domain. WASP Tg microglia were impaired in production of inflammatory cytokines such as tumor necrosis factor-alpha, IL-6 and IL-1beta upon LPS stimulation, whereas anti-inflammatory IL-10 production was significantly enhanced. Also, LPS-induced phosphorylation of nuclear factor kappaB was reduced in WASP Tg microglia. Furthermore, WASP Tg microglia exhibited less cytotoxicity against co-cultured neurons after stimulation by LPS and IFN-gamma, with a concordant decrease in nitric oxide production. These results strongly suggest that WASP may have pivotal roles through the EVH1 domain in the LPS signaling cascade, either directly or indirectly, and modulates inflammatory immune responses in microglia.}, Author = {Sato, Mitsuru and Ogihara, Kazumasa and Sawahata, Ryoko and Sekikawa, Kenji and Kitani, Hiroshi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0953-8178}, Journal = {Int Immunol}, Keywords = {research support, non-u.s. gov't;11 Glia;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8916182}, Number = {8}, Organization = {Transgenic Animal Research Center, National Institute of Agrobiological Sciences, 1-2 Ohwashi, Tsukuba, Ibaraki 305-8634, Japan. sato\_mitsuru\@affrc.go.jp}, Pages = {901-11}, Pii = {dxm074}, Pubmed = {17698982}, Title = {Impaired LPS-induced signaling in microglia overexpressing the Wiskott-Aldrich syndrome protein N-terminal domain}, Uuid = {44646809-B493-4A56-9891-C96EC8387952}, Volume = {19}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/intimm/dxm074}} @article{Sato:2007, Abstract = {In order to understand the functional maturation of the CNS, it is essential to first describe the functional maturation of sensory processing. We have approached this topic by following the ontogenetic patterning of neural circuit formation related to cranial and spinal sensory input using voltage-sensitive dye imaging. In previous studies, we have described the functional maturation of synapses in brainstem/midbrain neural circuits. Here, we elucidate the functional maturation of forebrain circuits by investigating neural networks related to the olfactory nerve (N. I) of chicken embryo. In the isolated N. I-olfactory bulb-forebrain preparation, application of electrical stimulation to N. I elicited excitatory postsynaptic potential (EPSP)-related slow optical signals in the olfactory bulb. The slow signal was mainly mediated by glutamate, and was easily fatigued with repetitive stimuli because of the immaturity of synapses in the embryonic CNS. Ontogenetically, the slow signal was detected from the 6-day embryonic stage, suggesting that functional synaptic connections between N. I and olfactory bulb emerge around this stage. In addition, from the 8-day embryonic stage, another response area was discriminated within the forebrain, which corresponded to the higher-ordered nucleus of the olfactory pathway. In comparison with our previous studies concerning the functional development of other cranial nerve-related sensory nuclei in the embryonic brainstem and midbrain, these results suggest that the olfactory pathway is functionally generated in the early stages of development when neural networks related to other visceral and somatic sensory inputs are also in the process of developing.}, Author = {Sato, K. and Kinoshita, M. and Momose-Sato, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Optics;Excitatory Postsynaptic Potentials;Electric Stimulation;Animals;Synapses;Aging;Neural Pathways;Glutamic Acid;Synaptic Transmission;Olfactory Nerve;research support, non-u.s. gov't;Time Factors;Olfactory Bulb;Prosencephalon;Chick Embryo;Olfactory Pathways;21 Neurophysiology;Carbocyanines;24 Pubmed search results 2008;Brain Mapping}, Month = {2}, Nlm_Id = {7605074}, Number = {4}, Organization = {Department of Physiology, Tokyo Medical and Dental University, Graduate School and Faculty of Medicine, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan. katsushige.phy2\@tmd.ac.jp}, Pages = {1334-46}, Pii = {S0306-4522(06)01520-X}, Pubmed = {17184922}, Title = {Optical mapping of spatiotemporal emergence of functional synaptic connections in the embryonic chick olfactory pathway}, Uuid = {79196C07-D616-4252-9D70-563D3A2B9403}, Volume = {144}, Year = {2007}, url = {papers/Sato_Neuroscience2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2006.11.019}} @article{Satoh:2000, Abstract = {The effects of activin A were investigated on the development of a multipotent neural stem cell line (MEB5) and an astrocyte progenitor cell line (AP-16) that were established from murine central nervous system (CNS). Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis demonstrated that each cell line expresses both type I and type II activin receptors and signaling molecules for activin, Smad2, Smad3, and Smad4. Activin A did not affect the proliferation of MEB5 and AP-16 cells. When each cell line was treated alone with activin A, glial fibrillary acidic protein (GFAP), a marker for astrocytes, was induced in AP-16 cells, but not in MEB5 cells. However, activin A accelerated the leukemia inhibitory factor (LIF)-induced astroglial differentiation of MEB5 cells. These results suggest that activin promotes astrocyte differentiation of CNS neural progenitors, and the competence to activin is different between multipotent stem cells and unipotent astrocyte progenitor cells.}, Author = {Satoh, M. and Sugino, H. and Yoshida, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Neurosci Lett}, Keywords = {Activin Receptors, Type II;Glial Fibrillary Acidic Protein/metabolism;Cell Differentiation/*drug effects;DNA-Binding Proteins/genetics;RNA, Messenger/analysis/genetics;Stem Cells/cytology/*drug effects;Neurons/cytology/*drug effects;Receptors, Growth Factor/genetics;Astrocytes/cytology/*drug effects;Animal;C abstr;Mice, Inbred C3H;Activin Receptors, Type I;Activins;Cell Line;Support, Non-U.S. Gov't;Central Nervous System/*cytology/drug effects;Inhibins/*pharmacology;04 Adult neurogenesis factors;Growth Inhibitors/pharmacology;Mice;Lymphokines/pharmacology;Trans-Activators/genetics;Cell Division/drug effects}, Number = {3}, Organization = {Animal Cell Bank, Institute for Fermentation, Osaka (IFO), 2-17-85 Juso- honmachi, Yodogawa-ku, Osaka, Japan. satoh-motonobu\@ifo.or.jp}, Pages = {143-6.}, Title = {Activin promotes astrocytic differentiation of a multipotent neural stem cell line and an astrocyte progenitor cell line from murine central nervous system}, Uuid = {1D167BE4-4B96-4880-9011-5133CC956DAB}, Volume = {284}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10773419}} @article{Saura:2003, Abstract = {Microglia can be isolated with high purity but low yield by shaking off loosely adherent cells from mixed glial cultures. Here we describe a new technique for isolating microglia with an average yield close to 2,000,000 microglial cells/mouse pup, more than five times higher than that of the shaking method. Confluent mixed glial cultures are subjected to mild trypsinization (0.05-0.12\%) in the presence of 0.2-0.5 mM EDTA and 0.5-0.8 mM Ca2+. This results in the detachment of an intact layer of cells containing virtually all the astrocytes, leaving undisturbed a population of firmly attached cells identified as >98\%microglia. These almost pure microglial preparations can be kept in culture for weeks and show proliferation and phagocytosis. Treatment with macrophage colony-stimulating factor and lipopolysaccharide, alone or in the presence of interferon gamma, induces typical microglial responses in terms of proliferation, morphological changes, nuclear factor-kappaB translocation, NO, and tumor necrosis alpha release and phagocytosis. This method allows for the preparation of highly enriched mouse or rat microglial cultures with ease and reproducibility. Because of its high yield, it can be especially convenient when high amounts of microglial protein/mRNA are required or in cases in which the starting material is limited, such as microglial cultures from transgenic animals.}, Author = {Saura, Josep and Tusell, Josep Maria and Serratosa, Joan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Trypsin;Cells, Cultured;Cell Separation;Tumor Necrosis Factor;NF-kappa B;Mice, Inbred C57BL;Cell Division;Cell Count;11 Glia;Microglia;Not relevant;Nitric Oxide;Mice;Support, Non-U.S. Gov't;Phagocytosis;Animals;Brain}, Medline = {22964698}, Month = {12}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Pharmacology and Toxicology, Institut d'Investigacions Biom\`{e}diques de Barcelona, IIBB-CSIC, Barcelona, Spain. jsafat\@iibb.csic.es}, Pages = {183-9}, Pubmed = {14603460}, Title = {High-yield isolation of murine microglia by mild trypsinization}, Uuid = {522AE522-755E-4747-82AD-9975FCAA6AD8}, Volume = {44}, Year = {2003}, url = {papers/Saura_Glia2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10274}} @article{Sawamoto:2001, Abstract = {Mesencephalic precursor cells may one day provide dopaminergic neurons for the treatment of Parkinson's disease. However, the generation of dopaminergic neurons from mesencephalic precursors has been difficult to follow, partly because an appropriate means for recognizing mesencephalic ventricular zone precursors has not been available. To visualize and isolate mesencephalic precursor cells from a mixed population, we used transgenic mice and rats carrying green fluorescent protein (GFP) cDNA under the control of the nestin enhancer. nestin- driven GFP was detected in the mesencephalic ventricular zone, and it colocalized with specific markers for neural precursor cells. In addition, data from flow-cytometry indicated that Prominin/CD133, a cell-surface marker for ventricular zone cells, was expressed specifically in these GFP-positive (GFP(+)) cells. After sorting by fluorescence-activated cell sorting, the GFP(+) cells proliferated in vitro and expressed precursor cell markers but not neuronal markers. Using clonogenic sphere formation assays, we showed that this sorted population was enriched in multipotent precursor cells that could differentiate into both neurons and glia. Importantly, many neurons generated from nestin-GFP-sorted mesencephalic precursors developed a dopaminergic phenotype in vitro. Finally, nestin-GFP(+) cells were transplanted into the striatum of a rat model of Parkinson's disease. Bromodeoxyuridine-tyrosine hydroxylase double-labeling revealed that the transplanted cells generated new dopaminergic neurons within the host striatum. The implanted cells were able to restore dopaminergic function in the host striatum, as assessed by a behavioral measure: recovery from amphetamine-induced rotation. Together, these findings indicate that precursor cells harvested from the embryonic ventral mesencephalon can generate dopaminergic neurons able to restore function to the chemically denervated adult striatum.}, Author = {Sawamoto, K. and Nakao, N. and Kakishita, K. and Ogawa, Y. and Toyama, Y. and Yamamoto, A. and Yamaguchi, M. and Mori, K. and Goldman, S. A. and Itakura, T. and Okano, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci}, Keywords = {Mesencephalon/cytology/embryology/*transplantation;Intermediate Filament Proteins/genetics/*metabolism;Disease Models, Animal;Male;Cells, Cultured;Flow Cytometry;03 Adult neurogenesis progenitor source;Recombinant Fusion Proteins/genetics/*metabolism;Transgenes;Brain Tissue Transplantation;Cell Differentiation/physiology;Oxidopamine;Support, U.S. Gov't, P.H.S.;Luminescent Proteins/genetics;Animal;Rats, Sprague-Dawley;Brain/pathology/surgery;Fetal Tissue Transplantation;Graft Survival;Colony-Forming Units Assay;02 Adult neurogenesis migration;Rats;BB;Neurons/cytology/*metabolism;Female;Membrane Glycoproteins/biosynthesis;Mice;Treatment Outcome;Stem Cells/cytology/metabolism/*transplantation;Dopamine/biosynthesis;Support, Non-U.S. Gov't;Animals, Transgenic;Parkinsonian Disorders/chemically induced/*therapy}, Number = {11}, Organization = {Division of Neuroanatomy, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.}, Pages = {3895-903.}, Title = {Generation of dopaminergic neurons in the adult brain from mesencephalic precursor cells labeled with a nestin-GFP transgene}, Uuid = {42270861-99A5-4A32-9619-8D8B202438B0}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11356877%20http://www.jneurosci.org/cgi/content/full/21/11/3895%20http://www.jneurosci.org/cgi/content/abstract/21/11/3895}} @article{Saxe:2006, Abstract = {Although hippocampal neurogenesis has been described in many adult mammals, the functional impact of this process on physiology and behavior remains unclear. In the present study, we used two independent methods to ablate hippocampal neurogenesis and found that each procedure caused a limited behavioral deficit and a loss of synaptic plasticity within the dentate gyrus. Specifically, focal X irradiation of the hippocampus or genetic ablation of glial fibrillary acidic protein-positive neural progenitor cells impaired contextual fear conditioning but not cued conditioning. Hippocampal-dependent spatial learning tasks such as the Morris water maze and Y maze were unaffected. These findings show that adult-born neurons make a distinct contribution to some but not all hippocampal functions. In a parallel set of experiments, we show that long-term potentiation elicited in the dentate gyrus in the absence of GABA blockers requires the presence of new neurons, as it is eliminated by each of our ablation procedures. These data show that new hippocampal neurons can be preferentially recruited over mature granule cells in vitro and may provide a framework for how this small cell population can influence behavior.}, Author = {Saxe, Michael D. and Battaglia, Fortunato and Wang, Jing-Wen W. and Malleret, Gael and David, Denis J. and Monckton, James E. and Garcia, A. Denise R. and Sofroniew, Michael V. and Kandel, Eric R. and Santarelli, Luca and Hen, Ren{\'e} and Drew, Michael R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Conditioning (Psychology);Glial Fibrillary Acidic Protein;Hippocampus;Neuronal Plasticity;Fear;Memory;Mice, Transgenic;Electrophysiology;Thymidine Kinase;Animals;Male;Mice;Neurons;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {7505876}, Number = {46}, Organization = {Center For Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.}, Pages = {17501-6}, Pii = {0607207103}, Pubmed = {17088541}, Title = {Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus}, Uuid = {8CF6207C-8B1C-4DD2-B137-9A77C7E239D5}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0607207103}} @article{Saxe:2007, Abstract = {To explore the function of adult hippocampal neurogenesis, we ablated cell proliferation by using two independent and complementary methods: (i) a focal hippocampal irradiation and (ii) an inducible and reversible genetic elimination of neural progenitor cells. Previous studies using these methods found a weakening of contextual fear conditioning but no change in spatial reference memory, suggesting a supportive role for neurogenesis in some, but not all, hippocampal-dependent memory tasks. In the present study, we examined hippocampal-dependent and -independent working memory using different radial maze tasks. Surprisingly, ablating neurogenesis caused an improvement of hippocampal-dependent working memory when repetitive information was presented in a single day. These findings suggest that adult-born cells in the dentate gyrus have different, and in some cases, opposite roles in distinct types of memory.}, Author = {Saxe, Michael D. and Malleret, Ga{\"e}l and Vronskaya, Svetlana and Mendez, Indira and Garcia, A. Denise and Sofroniew, Michael V. and Kandel, Eric R. and Hen, Ren{\'e}}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {01 Adult neurogenesis general;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7505876}, Number = {11}, Organization = {*Center for Neurobiology and Behavior and Howard Hughes Medical Institute, Columbia University, 722 West 168th Street, New York, NY 10032.}, Pages = {4642-6}, Pii = {0611718104}, Pubmed = {17360577}, Title = {Paradoxical influence of hippocampal neurogenesis on working memory}, Uuid = {41943302-B19A-4EFA-8239-847B22D68AC5}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0611718104}} @article{Scaradavou:1997, Abstract = {The purposes of the research reported here were first to explore a murine model for human placental and umbilical cord blood transplantation and second to evaluate the engraftment ability of ex vivo cultured hematopoietic cells. Murine near-term fetal and neonatal peripheral blood (FNPB) cells, genetically marked with the human multiple drug resistance transgene (MDR1) were used for syngeneic transplants into sublethally irradiated adult mice. Donor cells were transplanted either fresh and untreated, or after ex vivo culture in the presence of the hematopoietic growth factors recombinant murine stem cell factor, recombinant human interleukin-3 (rHu IL-3), and rHu IL-6, in a liquid culture system. To evaluate, count, and characterize FNPB progenitor cell-derived colonies, neonatal mouse mononuclear cells were cultured directly in methylcellulose with growth factors. To assess their ex vivo expansion ability, FNPB mononuclear cells were first cultured in liquid medium for 3 to 8 days and then transferred to semisolid assay plates. Evaluation of the cell counts after liquid culture showed a 1.4- to 11.6-fold increase, and the numbers of colonies observed in methylcellulose were similar to those produced by fresh FNPB cells. Donor-type engraftment was demonstrated by polymerase chain reaction (PCR) amplification of the human MDR1 transgene in the peripheral blood of all surviving animals (5 of 7 recipients of the fresh, and 3 of 8 recipients of the ex vivo-cultured cells) 2 to 4 months after transplantation. The proportion of donor leukocytes in the peripheral blood of the recipients (chimerism) was evaluated using fluorescence in situ hybridization (FISH) analysis 4 to 6 months after transplantation and ranged from 2\%to 26\%. In addition, bone marrow cultures were obtained from two recipient animals: one had received fresh-untreated cells and was evaluated 8 months after transplant, the other had received ex vivo cultured cells and was tested 14 months after grafting. The derived hematopoietic colonies were tested by PCR and the transgene was detected, conclusively proving long-term engraftment of donor cells. These results indicate that FNPB transplants can be successfully performed in sublethally irradiated mice with and without ex vivo culture. Long-term donor-type engraftment with sustained chimerism has been demonstrated. Thus, murine neonatal blood grafts can be used as an animal model for cord blood transplantation for gene therapy studies where complete myeloablation is not desirable and partial replacement of defective marrow may be sufficient. Furthermore, the possibility of numerically expanding hematopoietic progenitor cells contained in neonatal blood without affecting their engraftment ability could facilitate use of cord blood grafts in adult recipients.}, Author = {Scaradavou, A. and Isola, L. and Rubinstein, P. and Galperin, Y. and Najfeld, V. and Berlin, D. and Gordon, J. and Weinberg, R. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Animals;Colony-Forming Units Assay;Humans;Cells, Cultured;Bone Marrow Transplantation;Models, Biological;Female;Mice, Transgenic;11 Glia;Methylcellulose;Male;Hematopoietic Stem Cell Transplantation;Leukocyte Count;Radiation Chimera;Mice, Inbred Strains;Research Support, U.S. Gov't, P.H.S.;Leukocyte Transfusion;Survival Analysis;Animals, Newborn;Fetal Blood;Mice;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {97180166}, Month = {2}, Nlm_Id = {7603509}, Number = {3}, Organization = {Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, USA.}, Pages = {1089-99}, Pubmed = {9028342}, Title = {A murine model for human cord blood transplantation: near-term fetal and neonatal peripheral blood cells can achieve long-term bone marrow engraftment in sublethally irradiated adult recipients}, Uuid = {13CF6F38-8477-48AE-9028-0C3BD851E5C2}, Volume = {89}, Year = {1997}} @article{Scerri:2005, Abstract = {RATIONALE: Nicotine is reported to improve learning and memory in experimental animals. Improved learning and memory has also been related to increased neurogenesis in the dentate gyrus (DG) of the hippocampal formation. Surprisingly, recent studies suggest that self-administered nicotine depresses cell proliferation in the DG. OBJECTIVE: To test the hypothesis that the effects of nicotine on cell proliferation in the DG and learning and memory depend upon the nicotine dose administered. METHODS: Rats were chronically infused from subcutaneous osmotic mini pumps with nicotine (0.25 or 4 mg kg(-1) day(-1)) or the saline vehicle for 10 days. Half the rats in each treatment group were trained to locate a hidden platform in a water maze task on days 4-7; a probe trial was performed on day 8. The remaining rats remained in their home cages. The effects of nicotine and of training in the water maze task on cell genesis in the DG were determined by measuring 5-bromo-2'-deoxyuridine (BrDU) uptake using fluorescence immunohistochemistry. RESULTS: Training in the water maze task increased cell proliferation in the DG. Infusions of nicotine at 4 mg kg(-1) day(-1), but not 0.25 mg kg(-1) day(-1), decreased cell proliferation in both untrained animals and animals trained in the maze and impaired spatial learning. CONCLUSIONS: The data suggest that learning in the water maze task is impaired by higher doses of nicotine tested, and that this response may be related to reduced cell genesis in the DG.}, Author = {Scerri, and Stewart, and Breen, and Balfour,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0033-3158}, Journal = {Psychopharmacology (Berl)}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7608025}, Organization = {Section of Psychiatry and Behavioural Sciences, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY, UK, d.j.k.balfour\@dundee.ac.uk.}, Pages = {1-7}, Pubmed = {16025316}, Title = {The effects of chronic nicotine on spatial learning and bromodeoxyuridine incorporation into the dentate gyrus of the rat}, Uuid = {ADFD5F91-E269-49F5-8B84-3E636ADB8639}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1007/s00213-005-0086-4}} @article{Schafer:2006, Abstract = {The interactions of volatile odorants with the approximately 1000 types of olfactory receptor neurons in the olfactory mucosa are represented in the olfactory bulb by glomerular spatial activity maps. If these spatial maps underlie the perceptual identification of odorants then, for a given organism, they must be both specific and reproducible. However, this intra-organism reproducibility need not be present between organisms because genetic and developmental studies of olfactory bulb wiring suggest that there is substantial variation between the glomerular arrangements of closely related organisms and even between the two bulbs in a given animal. The ability of functional MRI (fMRI) to record responses of the entire rodent olfactory bulb repeatedly within the same subject has made it possible to assess the reproducibility of odor-induced spatial activity maps both within and between subjects exposed to equivalent stimuli. For a range of odorants, representing multiple chemical classes, a level of fMRI reproducibility (at 7.0 T and 9.4 T) comparable or superior to other cortical regions was demonstrated. While the responses of different bulbs to the same odorant could be localized within the same broad regions of the glomerular sheet, the precise magnitude and topology of the response within those regions were both often highly variable. These results demonstrate the robustness of high-field fMRI as a tool for assaying olfactory bulb function and provide evidence that equivalent perceptual outcomes may arise from divergent neural substrates.}, Author = {Schafer, and Kida, and Xu, and Rothman, and Hyder,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1053-8119}, Journal = {Neuroimage}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9215515}, Organization = {Department of Neurobiology, Magnetic Resonance Research Center (MRRC), Yale University, New Haven, CT 06510, USA.}, Pii = {S1053-8119(06)00009-7}, Pubmed = {16632382}, Title = {Reproducibility of odor maps by fMRI in rodents}, Uuid = {047A1537-4052-4672-8708-FDC83C7E7E1B}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2005.12.060}} @article{Scharff:2000, Abstract = {In the high vocal center (HVC) of adult songbirds, increases in spontaneous neuronal replacement correlate with song changes and with cell death. We experimentally induced death of specific HVC neuron types in adult male zebra finches using targeted photolysis. Induced death of a projection neuron type that normally turns over resulted in compensatory replacement of the same type. Induced death of the normally nonreplaced type did not stimulate their replacement. In juveniles, death of the latter type increased recruitment of the replaceable kind. We infer that neuronal death regulates the recruitment of replaceable neurons. Song deteriorated in some birds only after elimination of replaceable neurons. Behavioral deficits were transient and followed by variable degrees of recovery. This raises the possibility that induced neuronal replacement can restore a learned behavior.}, Author = {Scharff, C. and Kirn, J. R. and Grossman, M. and Macklis, J. D. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Neuron}, Keywords = {Brain/cytology/physiology;Porphyrins;Cell Division/physiology;Songbirds/*physiology;Neurons/*cytology/physiology;06 Adult neurogenesis injury induced;Cell Death/physiology;Animal;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Nerve Degeneration/chemically induced/physiopathology;D-11;Support, Non-U.S. Gov't;Vocalization, Animal/*physiology;Age Factors;Learning/physiology;Male}, Number = {2}, Organization = {Department of Animal Behavior, The Rockefeller University, New York, New York 10021, USA. scharfc\@rockvax.rockefeller.edu}, Pages = {481-92.}, Title = {Targeted neuronal death affects neuronal replacement and vocal behavior in adult songbirds}, Uuid = {0A1A36FA-0EA4-40FC-8EB1-935DF4EC78B8}, Volume = {25}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10719901}} @article{Scheiffele:2000, Abstract = {Most neurons form synapses exclusively with other neurons, but little is known about the molecular mechanisms mediating synaptogenesis in the central nervous system. Using an in vitro system, we demonstrate that neuroligin-1 and -2, postsynaptically localized proteins, can trigger the de novo formation of presynaptic structure. Nonneuronal cells engineered to express neuroligins induce morphological and functional presynaptic differentiation in contacting axons. This activity can be inhibited by addition of a soluble version of beta-neurexin, a receptor for neuroligin. Furthermore, addition of soluble beta-neurexin to a coculture of defined pre- and postsynaptic CNS neurons inhibits synaptic vesicle clustering in axons contacting target neurons. Our results suggest that neuroligins are part of the machinery employed during the formation and remodeling of CNS synapses.}, Author = {Scheiffele, P. and Fan, J. and Choih, J. and Fetter, R. and Serafini, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Synapses;Cell Differentiation;10 Development;research support, non-u.s. gov't;Membrane Proteins;Nerve Tissue Proteins;Gene Expression Regulation;10 circuit formation;Coculture Techniques;COS Cells;Animals;Humans;24 Pubmed search results 2008;Neurons}, Month = {6}, Nlm_Id = {0413066}, Number = {6}, Organization = {Department of Molecular and Cell Biology, University of California, Berkeley 94720, USA. scheiffe\@uclink4.berkeley.edu}, Pages = {657-69}, Pii = {S0092-8674(00)80877-6}, Pubmed = {10892652}, Title = {Neuroligin expressed in nonneuronal cells triggers presynaptic development in contacting axons}, Uuid = {6BAFB064-D8D4-4BA6-AD85-432452A3222A}, Volume = {101}, Year = {2000}, url = {papers/Scheiffele_Cell2000.pdf}} @article{Schermer:2002, Abstract = {Cytokines play an important role in the regulation of proliferation and migration in the central nervous system. The aim of this study was to determine if granulocyte macrophage-colony stimulating factor (GM-CSF) activates cells in the cortex of organotypic brain slice cultures. Our data show that murine GM-CSF markedly stimulated the proliferation and migration of small round microglia from a cortex slice. These round cells were strongly positive for integrin CD11b (OX-42), isolectin B4-lectin-binding, the monocytic marker ED1 and partly expressed major histocompatibility complex (MHC) class II antigen (OX-6). Only some differentiated microglia were visible which expressed the integrin CD11c and MHCII. GM-CSF enhanced the proliferation as analyzed by bromodeoxyuridine incorporation. The number of migrated cells decreased during culturing and enhanced terminal dUTP nick-end labelling positive nuclei were found. Taken together, our data conclude that GM-CSF is an important cytokine, which regulates the proliferation and migration of cortical microglia.}, Author = {Schermer, Christine and Humpel, Christian}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Cell Differentiation;Signal Transduction;Animals;Rats;Microglia;Immunologic Surveillance;Cell Movement;11 Glia;Granulocyte-Macrophage Colony-Stimulating Factor;Animals, Newborn;Support, Non-U.S. Gov't;Membrane Glycoproteins;Cerebral Cortex;Cell Division;Immunohistochemistry;Membrane Proteins;Organ Culture;Lectins;Histocompatibility Antigens Class II}, Medline = {22129465}, Month = {8}, Nlm_Id = {7600130}, Number = {2}, Organization = {Laboratory of Psychiatry, Department of Psychiatry, University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.}, Pages = {180-4}, Pii = {S0304394002004962}, Pubmed = {12133583}, Title = {Granulocyte macrophage-colony stimulating factor activates microglia in rat cortex organotypic brain slices}, Uuid = {F31A27E2-C3EC-458C-AC2E-5D944B0EB8A9}, Volume = {328}, Year = {2002}, url = {papers/Schermer_NeurosciLett2002.pdf}} @article{Schiefer:1999, Abstract = {Microglial motility was studied in living mammalian brain tissue using infrared gradient contrast microscopy in combination with video contrast enhancement and time lapse video recording. The infrared gradient contrast allows the visualization of living cells up to a depth of 60 microm in brain slices, in regions where cell bodies remain largely uninjured by the tissue preparation and are visible in their natural environment. In contrast to other techniques, including confocal microscopy, this procedure does not require any staining or labeling of cell membranes and thus guarantees the investigation of tissue which has not been altered, apart from during preparation. Microglial cells are activated and increase in number in the facial nucleus following peripheral axotomy. Thus we established the preparation of longitudinal rat brainstem slices containing the axotomized facial nucleus as a source of activated microglial cells. During prolonged video time lapse recordings, two different types of microglial cell motility could be observed. Microglial cells which had accumulated at the surface of the slice remained stationary but showed activity of the cell soma, developing pseudopods of different shape and size which undulated and which were used for phagocytosis of cell debris. Microglial phagocytosis of bacteria could be documented for the first time in situ. In contrast, ameboid microglia which did not display pseudopods but showed migratory capacity, could be observed exclusively in the depth of the tissue. Some of these cells maintained a close contact to neurons and appeared to move along their dendrites, a finding that may be relevant to the role of microglia in "synaptic stripping", the displacement of synapses following axotomy. This approach provides a valuable opportunity to investigate the interactions between activated microglial cells and the surrounding cellular and extracellular structures in the absence of staining or labeling, thus opening a wide field for the analysis of the cellular mechanisms involved in numerous pathologies of the CNS.}, Author = {Schiefer, J. and Kampe, K. and Dodt, H. U. and Zieglg{\"a}nsberger, W. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Solitary Nucleus;Brain Stem;Image Processing, Computer-Assisted;Facial Nerve;Motor Neurons;Rats;Not relevant;Rats, Wistar;Microscopy, Video;11 Glia;Microglia;In Vitro;Axotomy;Animals;Cell Movement;Male}, Medline = {20229902}, Month = {6}, Nlm_Id = {0364620}, Number = {6}, Organization = {Department of Neurology, Technical University Aachen, Pauwelsstr. 30, D-52057 Aachen, Germany.}, Pages = {439-53}, Pubmed = {10767097}, Title = {Microglial motility in the rat facial nucleus following peripheral axotomy}, Uuid = {B1B72030-38A8-456D-BBDC-455265FD995E}, Volume = {28}, Year = {1999}} @article{Schiffer:2006, Abstract = {Nestin is a marker of early stages of neurocytogenesis. It has been studied in 50 neuroepithelial tumors, mostly gliomas of different malignancy grades, by immunohistochemistry, immunofluorescence, immunoblotting, and confocal microscopy and compared with GFAP and Vimentin. As an early marker of differentiation, Nestin is almost not expressed in diffuse astrocytomas, variably expressed in anaplastic astrocytomas and strongly and irregularly expressed in glioblastomas. Negative in oligodendrogliomas, it stains ependymomas and shows a gradient of expression in pilocytic astrocytomas. In glioblastomas, Nestin distribution does not completely correspond to that of GFAP and Vimentin with which its expression varies in tumor cells in a complementary way, as confirmed by confocal microscopy. Tumor cells can thus either derive from or differentiate toward the neurocytogenetic stages. Hypothetically, they could be put in relation with radial glia where during embriogenesis the three antigens are successively expressed. Completely negative cells of invasive or recurrent glioblastomas may represent malignant selected clones after accumulation of mutations or early stem cells not expressing antigens.}, Author = {Schiffer, and Manazza, and Tamagno,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7600130}, Organization = {Foundation Policlinico di Monza, Neuro-bio-oncology Center (Vercelli)/University of Turin, Italy.}, Pii = {S0304-3940(06)00138-8}, Pubmed = {16529857}, Title = {Nestin expression in neuroepithelial tumors}, Uuid = {BD31C835-285A-4746-9456-009BA3B4A707}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2006.02.034}} @article{Schiller:2004, Abstract = {Epileptic seizures are composed of recurrent bursts of intense firing separated by periods of electrical quiescence. The mechanisms responsible for sustaining seizures and generating recurrent bursts are yet unclear. Using whole cell voltage recordings combined with intracellular calcium fluorescence imaging from bicuculline (BCC)-treated neocortical brain slices, I showed isolated paroxysmal depolarization shift (PDS) discharges were followed by a sustained afterdepolarization waveform (SADW) with an average peak amplitude of 3.3 +/- 0.9 mV and average half-width of 6.2 +/- 0.6 s. The SADW was mediated by the calcium-activated nonspecific cation current (I(can)) as it had a reversal potential of -33.1 +/- 6.8 mV, was unaffected by changing the intracellular chloride concentrations, was markedly diminished by buffering [Ca(2+)](i) with intracellular bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), and was reversibly abolished by the I(can) blocker flufenamic acid (FFA). The Ca(2+) influx responsible for activation of I(can) was mediated by both N-methyl-d-aspartate-receptor channels, voltage-gated calcium channels and, to a lesser extent, internal calcium stores. In addition to isolated PDS discharges, BCC-treated brain slices also produced seizure-like events, which were accompanied by a prolonged depolarizing waveform underlying individual ictal bursts. The similarities between the initial part of this waveform and the SADW and the fact it was markedly reduced by buffering [Ca(2+)](i) with BAPTA strongly suggested it was mediated, at least in part, by I(can). Addition of FFA reversibly eliminated recurrent bursting, and transformed seizure-like events into isolated PDS responses. These results indicated I(can) was activated during epileptiform discharges and probably participated in sustaining seizure-like events.}, Author = {Schiller, Yitzhak}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Epilepsy;Electric Conductivity;Research Support, Non-U.S. Gov't;Ion Channels;21 Neurophysiology;Rats;Time Factors;Calcium;Cations;In Vitro;21 Calcium imaging;Neocortex;Electrophysiology;Rats, Wistar;Animals;24 Pubmed search results 2008;Flufenamic Acid}, Month = {8}, Nlm_Id = {0375404}, Number = {2}, Organization = {Department of Technology, Rambam Medical Center, 1 Efron St., P.O.B 9602 Haifa, Israel 31096. y\_schiller\@yahoo.com}, Pages = {862-72}, Pii = {92/2/862}, Pubmed = {15277598}, Title = {Activation of a calcium-activated cation current during epileptiform discharges and its possible role in sustaining seizure-like events in neocortical slices}, Uuid = {B31FFC1F-3ABF-4E4F-A372-64353385D073}, Volume = {92}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00972.2003}} @article{Schiller:1995, Abstract = {1. Simultaneous measurements of intracellular free calcium concentration ([Ca2+]i) and intrasomatic and intradendritic membrane potential (Vm) were performed using fura-2 fluorimetry and whole-cell recording in neocortical layer V pyramidal neurones in rat brain slices. 2. Back-propagating action potentials (APs) evoked [Ca2+]i transients in the entire neurone including the soma, the axon initial segment, the apical dendrite up to the distal tuft branches, and the oblique and basal dendrites, indicating that following suprathreshold activation the entire dendritic tree is depolarized sufficiently to open voltage-dependent calcium channels (VDCCs). 3. The [Ca2+]i transient peak evoked by APs showed large differences between various compartments of the neurone. Following a single AP, up to 6-fold differences were measured, ranging from 43 +/- 14 nM in the soma to 267 +/- 109 nM in the basal dendrites. 4. Along the main apical dendrite, the [Ca2+]i transients evoked by single APs or trains of APs had the largest amplitude and the fastest decay in the proximal region; the [Ca2+]i transient peak and decay time constant following a single AP were 128 +/- 25 nM and 420 +/- 150 ms, respectively, and following a train of five APs (at 10-12 Hz), 710 +/- 214 nM and 390 +/- 150 ms, respectively. The [Ca2+]i transients gradually decreased in amplitude and broadened in more distal portions of the apical dendrite up to the main bifurcation. 5. In the apical tuft branches, the profile of the [Ca2+]i transients was dependent on AP frequency.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Schiller, J. and Helmchen, F. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Fura-2;Fluorescence;Animals;Synapses;Rats;Sodium Channels;Axons;in vitro ;Pyramidal Cells;Rats, Wistar;Calcium;Tetrodotoxin;21 Calcium imaging;Dendrites;research support, non-u.s. gov't ;Action Potentials;Cerebral Cortex;21 Neurophysiology;Calcium Channels;24 Pubmed search results 2008;Calibration}, Month = {9}, Nlm_Id = {0266262}, Organization = {Max-Planck-Institut f{\"u}r Medizinische Forschung, Abteilung Zellphysiologie, Heidelberg, Germany.}, Pages = {583-600}, Pubmed = {8544123}, Title = {Spatial profile of dendritic calcium transients evoked by action potentials in rat neocortical pyramidal neurones}, Uuid = {2C84D145-3F06-46EA-A432-3AFF15324022}, Volume = {487 ( Pt 3)}, Year = {1995}} @article{Schiller:1997, Abstract = {1. Simultaneous whole-cell voltage and Ca2+ fluorescence measurements were made from the distal apical dendrites and the soma of thick tufted pyramidal neurons in layer 5 of 4-week-old (P28-32) rat neocortex slices to investigate whether activation of distal synaptic inputs can initiate regenerative responses in dendrites. 2. Dual whole-cell voltage recordings from the distal apical trunk and primary tuft branches (540-940 microns distal to the soma) showed that distal synaptic stimulation (upper layer 2) evoking a subthreshold depolarization at the soma could initiate regenerative potentials in distal branches of the apical tuft which were either graded or all-or-none. These regenerative potentials did not propagate actively to the soma and axon. 3. Calcium fluorescence measurements along the apical dendrites indicated that the regenerative potentials were associated with a transient increase in the concentration of intracellular free calcium ([Ca2+]i) restricted to distal dendrites. 4. Cadmium added to the bath solution blocked both the all-or-more dendritic regenerative potentials and local dendritic [Ca2+]i transients evoked by distal dendritic current injection. Thus, the regenerative potentials in distal dendrites represent local Ca2+ action potentials. 5. Initiation of distal Ca2+ action potentials by a synaptic stimulus required coactivation of AMPA- and NMDA-type glutamate receptor channels. 6. It is concluded that in neocortical layer 5 pyramidal neurons of P28-32 animals glutamatergic synaptic inputs to the distal apical dendrites can be amplified via local Ca2+ action potentials which do not reach threshold for axonal AP initiation. As amplification of distal excitatory synaptic input is associated with a localized increase in [Ca2+]i these Ca2+ action potentials could control the synaptic efficacy of the distal cortico-cortical inputs to layer 5 pyramidal neurons.}, Author = {Schiller, J. and Schiller, Y. and Stuart, G. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Fluorescence;Animals;Electric Conductivity;Rats;Neocortex;Excitatory Amino Acid Agonists;Patch-Clamp Techniques;in vitro ;Axons;Pyramidal Cells;Calcium;Dendrites;research support, non-u.s. gov't ;Action Potentials;21 Neurophysiology;Isoxazoles;24 Pubmed search results 2008;Propionates;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Month = {12}, Nlm_Id = {0266262}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut f{\"u}r medizinische Forschung, Heidelberg, Germany.}, Pages = {605-16}, Pubmed = {9457639}, Title = {Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons}, Uuid = {3EBFFE46-32DE-4200-A8EE-6F2181BACC98}, Volume = {505 ( Pt 3)}, Year = {1997}, url = {papers/Schiller_JPhysiol1997.pdf}} @article{Schilling:2003, Abstract = {Resident microglia and hematogenous macrophages play crucial roles in the pathogenetic cascade following cerebral ischemia but may functionally differ regarding neuroprotective and cytotoxic properties. Distinction between these cells has not been possible due to a lack of discriminating cellular markers. We generated bone marrow chimeric mice by transplanting bone marrow from green fluorescent protein (GFP) transgenic mice into irradiated wild-type recipients. Transient focal cerebral ischemia was induced by transient middle cerebral artery occlusion (MCAO) for 30 min. Resident microglia and infiltrating macrophages were identified by immunohistochemistry and GFP fluorescence after 1-28 days. The first blood-derived cells infiltrating the infarct area were seen on Day 1 and identified as granulocytes. Hematogenous GFP(+) macrophages were rarely observed on Day 2, reached peak numbers on Day 7, and decreased thereafter. In contrast, resident GFP(-) microglial cells rapidly became activated already on Day 1 after MCAO. Even on Days 4 and 7, most macrophage-like cells remained GFP(-), indicating their derivation from resident microglia. Hematogenous macrophages were able to acquire a ramified morphology indistinguishable from resident microglia while microglial cells could develop into a phagocytic phenotype indistinguishable from infiltrating macrophages. The vast majority of macrophages in the infarct area are derived from local microglia, revealing a remarkable predominance of local defense mechanisms over immune cells arriving from the blood. GFP bone marrow chimeric mice are a powerful tool to further differentiate the function of resident microglia and hematogenous macrophages following cerebral ischemia.}, Author = {Schilling, Matthias and Besselmann, Michael and Leonhard, Christine and Mueller, Marcus and Ringelstein, E. Bernd and Kiefer, Reinhard}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Animals;Astrocytes;Disease Progression;Macrophages;Bone Marrow Transplantation;Brain;Microglia;Cell Movement;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Male;Radiation Chimera;Disease Models, Animal;Mice;Luminescent Proteins;Immunohistochemistry;Ischemic Attack, Transient;Research Support, Non-U.S. Gov't}, Medline = {22838167}, Month = {9}, Nlm_Id = {0370712}, Number = {1}, Organization = {Department of Neurology, Universit{\"a}tsklinikum M{\"u}nster, M{\"u}nster, Germany.}, Pages = {25-33}, Pii = {S0014488603000827}, Pubmed = {12957485}, Title = {Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: a study in green fluorescent protein transgenic bone marrow chimeric mice}, Uuid = {597432AA-BF69-11DA-969D-000D9346EC2A}, Volume = {183}, Year = {2003}, url = {papers/Schilling_ExpNeurol2003.pdf}} @article{Schipke:2002, Abstract = {Pathologic impacts in the brain lead to a widespread activation of microglial cells far beyond the site of injury. Here, we demonstrate that glial Ca2+ waves can trigger responses in microglial cells. We elicited Ca2+ waves in corpus callosum glial cells by electrical stimulation or local adenosine triphosphate (ATP) ejection in acute brain slices. Macroglial cells, but not microglia, were bulk-loaded with Ca2+-sensitive dyes. Using a transgenic animal in which astrocytes were labeled by the enhanced green fluorescence protein (EGFP) allowed us to identify the reacting cell populations: the wave activated a Ca2+ response in both astrocytes and non-astrocytic glial cells and spread over hundreds of micrometers even into the adjacent cortical and ventricular cell layers. Regenerative ATP release and subsequent activation of metabotropic purinergic receptors caused the propagation of the glial Ca2+ wave: the wave was blocked by the purinergic receptor antagonist Reactive Blue 2 and was not affected by the gap junction blocker octanol, but enhanced in Ca2+ free saline. To test whether microglial cells respond to the wave, microglial cells were labeled with a dye-coupled lectin and membrane currents were recorded with the patch-clamp technique. When the wave passed by, a current with the characteristics of a purinergic response was activated. Thus, Ca2+ waves in situ are not restricted to astrocytic cells, but broadly activate different glial cell types.}, Author = {Schipke, Carola G. and Boucsein, Clemens and Ohlemeyer, Carsten and Kirchhoff, Frank and Kettenmann, Helmut}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {Electric Stimulation;Adenosine Triphosphate;Astrocytes;Calcium;In Vitro;11 Glia;Microglia;Calcium Signaling;Animals;Brain;Membrane Potentials;Mice}, Medline = {21676357}, Month = {2}, Nlm_Id = {8804484}, Number = {2}, Organization = {Max-Delbr{\"u}ck Center for Molecular Medicine, Cellular Neuroscience, D-13092 Berlin, Germany.}, Pages = {255-7}, Pii = {01-0514fje}, Pubmed = {11772946}, Title = {Astrocyte Ca2+ waves trigger responses in microglial cells in brain slices}, Uuid = {D01CF6DE-1B03-4AB4-A7AB-B8A1BD51EC96}, Volume = {16}, Year = {2002}, url = {papers/Schipke_FASEBJ2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.01-0514fje}} @article{Schlessinger:1975, Abstract = {The dentate gyrus of the rat contains about 600,000 granule cells. These small neurons are generated over a prolonged period from the 14th day of gestation until some time after the second postnatal week. The majority of the cells pass through their last phase of DNA synthesis in the postnatal period, and during the peak period of cell generation, between the fifth and seventh days after birth, up to 50,000 granule cells are formed each day. Contrary to earlier reports, most of the cells pass through their last mitotic division either within the stratum granulosum itself, or within the hilar region of the developing gyrus. The precursor population of cells in the hilar region must therefore constitute a pool of true neuroblasts. The origin of this pool of cells has not been definitely established but it seems probable that its cells are derived from the neuroepithelium lining the lateral ventricle adjacent to the region from which the hippocampal pyramidal cells are generated. Examination of the final location of granule cells labeled at different stages reveals three distinct morphogenetic gradients in the gyrus. The cells in the dorsal blade tend to be formed earlier than those in the ventral blade; cells in the more caudal (or temporal) portions of the gyrus are generated earlier than those in more rostral (or septal) regions; and in all regions the more superficial neurons in the stratum granulosum are formed earlier than the deeper granule cells. The bearing of some of these findings on the development and organization of the connections of the dentate gyrus is discussed.}, Author = {Schlessinger, A. R. and Cowan, W. M. and Gottlieb, D. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Thymidine;Female;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Autoradiography;Rats;Cell Count;DNA;Pregnancy;Tritium;Animals;Cell Movement;Neurons}, Medline = {75095907}, Month = {1}, Nlm_Id = {0406041}, Number = {2}, Pages = {149-75}, Pubmed = {1112911}, Title = {An autoradiographic study of the time of origin and the pattern of granule cell migration in the dentate gyrus of the rat}, Uuid = {579E6638-686D-11DA-A4B6-000D9346EC2A}, Volume = {159}, Year = {1975}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901590202}} @article{Schlief:2007, Abstract = {In both the vertebrate nose and the insect antenna, most olfactory receptor neurons (ORNs) respond to multiple odors. However, some ORNs respond to just a single odor, or at most to a few highly related odors. It has been hypothesized that narrowly tuned ORNs project to narrowly tuned neurons in the brain, and that these dedicated circuits mediate innate behavioral responses to a particular ligand. Here we have investigated neural activity and behavior downstream from two narrowly tuned ORN types in Drosophila melanogaster. We found that genetically ablating either of these ORN types impairs innate behavioral attraction to their cognate ligand. Neurons in the antennal lobe postsynaptic to one of these ORN types are, like their presynaptic ORNs, narrowly tuned to a pheromone. However, neurons postsynaptic to the second ORN type are broadly tuned. These results demonstrate that some narrowly tuned ORNs project to dedicated central circuits, ensuring a tight connection between stimulus and behavior, whereas others project to central neurons that participate in the ensemble representations of many odors.}, Author = {Schlief, Michelle L. and Wilson, Rachel I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Ave., Boston, Massachusetts 02115, USA.}, Pages = {623-30}, Pii = {nn1881}, Pubmed = {17417635}, Title = {Olfactory processing and behavior downstream from highly selective receptor neurons}, Uuid = {98FC3D69-784F-42B2-89D0-20F1986CAFDE}, Volume = {10}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1881}} @article{Schmid:2005, Abstract = {Extracellular matrix-like molecule reelin and cell surface adhesion receptors such as alpha3beta1 integrin can regulate neuronal migration and position in the developing cerebral cortex. Here we show that alpha3beta1 integrin binds to the N-terminal region of reelin, a site distinct from the region of reelin shown to associate with other reelin receptors such as VLDLR/ApoER2. Furthermore, Dab1, a member of the reelin signaling pathway, can complex with the cytoplasmic region of beta1 integrin in a reelin-dependent manner. Thus, alpha3beta1 integrin-reelin interactions may contribute to appropriate neuronal placement in the developing cerebral cortex.}, Author = {Schmid, and Jo, and Shelton, and Kreidberg, and Anton,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {10 Development}, Month = {2}, Nlm_Id = {9110718}, Organization = {UNC Neuroscience Center and the Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.}, Pii = {bhi041}, Pubmed = {15703255}, Title = {Reelin, Integrin and Dab1 Interactions during Embryonic Cerebral Cortical Development}, Uuid = {A1AFA11D-9BF3-40E6-A976-6C8B9BD4DE89}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhi041}} @article{Schmid:2004, Abstract = {We show that alpha3 integrin mutation disrupts distinct aspects of neuronal migration and placement in the cerebral cortex. The preplate develops normally in alpha3 integrin mutant mice. However, time lapse imaging of migrating neurons in embryonic cortical slices indicates retarded radial and tangential migration of neurons, but not ventricular zone-directed migration. Examination of the actin cytoskeleton of alpha3 integrin mutant cortical cells reveals aberrant actin cytoskeletal dynamics at the leading edges. Deficits are also evident in the ability of developing neurons to probe their cellular environment with filopodial and lamellipodial activity. Calbindin or calretinin positive upper layer neurons as well as the deep layer neurons of alpha3 integrin mutant mice expressing EGFP were misplaced. These results suggest that alpha3beta1 integrin deficiency impairs distinct patterns of neuronal migration and placement through dysregulated actin dynamics and defective ability to search and respond to migration modulating cues in the developing cortex.}, Author = {Schmid, and Shelton, and Stanco, and Yokota, and Kreidberg, and Anton,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {10 Development}, Nlm_Id = {8701744}, Number = {24}, Organization = {UNC Neuroscience Center and the Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.}, Pages = {6023-6031}, Pii = {dev.01532}, Pubmed = {15537685}, Title = {\{alpha\}3\{beta\}1 integrin modulates neuronal migration and placement during early stages of cerebral cortical development}, Uuid = {E32BA570-4229-477E-A249-6639D0F7A3F6}, Volume = {131}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.01532}} @article{Schmidt:2003, Abstract = {The mechanisms governing the kinetics of climbing fibre-mediated Ca2+ transients in spiny dendrites of cerebellar Purkinje cells (PCs) were quantified with high-resolution confocal Ca2+ imaging. Ca2+ dynamics in parvalbumin (PV-/-) and parvalbumin/calbindin D28k null-mutant (PV/CB-/-) mice were compared with responses in wild-type (WT) animals. In the WT, Ca2+ transients in dendritic shafts were characterised by double exponential decay kinetics that were not due to buffered Ca2+ diffusion or saturation of the indicator dye. Ca2+ transients in PV-/- PCs reached the same peak amplitude as in the WT but the biphasic nature of the decay was less pronounced, an effect that could be attributed to PV's slow binding kinetics. In contrast, peak amplitudes in PV/CB-/- PCs were about two times higher than in the WT and the decay became nearly monophasic. Numerical simulations indicate that the residual deviation from a single exponential decay in PV/CB-/- is due to saturation of the Ca2+ indicator dye. Furthermore, the simulations imply that the effect of uncharacterised endogenous Ca2+ binding proteins is negligible, that buffered diffusion and dye saturation significantly affects spineous Ca2+ transients but not those in the dendritic shafts, and that neither CB nor PV undergoes saturation in spines or dendrites during climbing fibre-evoked Ca2+ transients. Calbindin's medium-affinity binding sites are fast enough to reduce the peak amplitude of the Ca2+ signal. However, similar to PV, delayed binding by CB leads to biphasic Ca2+ decay kinetics. Our results suggest that the distinct kinetics of PV and CB underlie the biphasic kinetics of synaptically evoked Ca2+ transients in dendritic shafts of PCs.}, Author = {Schmidt, Hartmut and Stiefel, Klaus M. and Racay, Peter and Schwaller, Beat and Eilers, Jens}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Coloring Agents;Fluorescence;Purkinje Cells;Electrophysiology;Calcium Signaling;Osmolar Concentration;Animals;Microscopy, Confocal;in vitro ;Kinetics;Calcium;Calcium-Binding Protein, Vitamin D-Dependent;21 Calcium imaging;Dendrites;research support, non-u.s. gov't ;Microspheres;Mice, Knockout;21 Neurophysiology;Calcium-Binding Proteins;Parvalbumins;DNA Mutational Analysis;Diffusion;24 Pubmed search results 2008;Mice;Nerve Fibers;Intracellular Membranes}, Month = {8}, Nlm_Id = {0266262}, Number = {Pt 1}, Organization = {Department of Neurophysiology, Max-Planck-Institute for Brain Research, 60528 Frankfurt, Germany.}, Pages = {13-32}, Pii = {jphysiol.2002.035824}, Pubmed = {12813159}, Title = {Mutational analysis of dendritic Ca2+ kinetics in rodent Purkinje cells: role of parvalbumin and calbindin D28k}, Uuid = {14DD44E9-85F0-4BD0-A7B7-DD0CD039E28F}, Volume = {551}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2002.035824}} @article{Schmidt-Hieber:2004, Abstract = {Neural stem cells in various regions of the vertebrate brain continuously generate neurons throughout life. In the mammalian hippocampus, a region important for spatial and episodic memory, thousands of new granule cells are produced per day, with the exact number depending on environmental conditions and physical exercise. The survival of these neurons is improved by learning and conversely learning may be promoted by neurogenesis. Although it has been suggested that newly generated neurons may have specific properties to facilitate learning, the cellular and synaptic mechanisms of plasticity in these neurons are largely unknown. Here we show that young granule cells in the adult hippocampus differ substantially from mature granule cells in both active and passive membrane properties. In young neurons, T-type Ca2+ channels can generate isolated Ca2+ spikes and boost fast Na+ action potentials, contributing to the induction of synaptic plasticity. Associative long-term potentiation can be induced more easily in young neurons than in mature neurons under identical conditions. Thus, newly generated neurons express unique mechanisms to facilitate synaptic plasticity, which may be important for the formation of new memories.}, Author = {Schmidt-Hieber, Christoph and Jonas, Peter and Bischofberger, Josef}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Cell Aging;Long-Term Potentiation;Cell Differentiation;Animals;Synapses;In Vitro;Rats;Neuronal Plasticity;Memory;Calcium Channels, T-Type;Hippocampus;Rats, Wistar;Calcium;Male;Dendrites;01 Adult neurogenesis general;Support, Non-U.S. Gov't;Action Potentials;Sodium}, Month = {5}, Nlm_Id = {0410462}, Number = {6988}, Organization = {Physiologisches Institut der Universit{\"a}t Freiburg, D-79104 Freiburg, Germany.}, Pages = {184-7}, Pii = {nature02553}, Pubmed = {15107864}, Title = {Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus}, Uuid = {B4E3C892-1537-4FE4-AD2C-23FFB9B3B4BF}, Volume = {429}, Year = {2004}, url = {papers/Schmidt-Hieber_Nature2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature02553}} @article{Schmitt:1998, Abstract = {Microglial reactivity associated with induction of MHC class II (HLA-DR) antigen is a sensitive indicator for pathological events in the CNS. To assess the response of glial cells after lesions of supraspinal descending tracts, HLA-DR, CD68 and GFAP were studied immunohistochemically on spinal cord tissue of 5 patients who died after unilateral infarction of the middle cerebral artery territory, and 5 control cases. In patients who died shortly after a stroke (4-14 days) increased HLA-DR-immunoreactivity (HLA-DR-IR) could be observed in the intermediate grey matter and in the ventral horn. The CD68-IR was much less intense. After longer survival times (5 weeks to 4 months). HLA-DR-IR in the grey matter was clearly lower than that observed in the spinal cord of short survival times, but very abundant in the dorsolateral funiculus, specifically within the corticospinal tract. In white matter areas, CD68-IR was almost identical to the HLA-DR-IR. Within the grey matter, CD68-IR was similar to the control tissue. A moderate increase of GFAP-positive astrocytes could be seen only in the grey matter after longer survival times. It seems probable, that the dynamics of HLA-DR-positive microglia reflect the early phagocytosis of presynaptic terminals by microglia in target regions of descending fibre tracts. In the white matter, the removal of degenerating axons by phagocytosing microglia expressing HLA-DR and CD68 antigens is a slower process which occurs over a period of months.}, Author = {Schmitt, A. B. and Brook, G. A. and Buss, A. and Nacimiento, W. and Noth, J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Human;Antigens, Differentiation, Myelomonocytic;Middle Aged;Microglia;Female;Antigens, CD;Cerebral Infarction;Not relevant;11 Glia;Time Factors;Cerebrovascular Disorders;Aged;Male;Spinal Cord;Support, Non-U.S. Gov't;HLA-DR Antigens;Survival Analysis;Aged, 80 and over;Adult;Histocompatibility Antigens Class II;Glial Fibrillary Acidic Protein}, Medline = {98382909}, Month = {6}, Nlm_Id = {7609829}, Number = {3}, Organization = {Department of Neurology, Technical University, School of Medicine, Aachen, Germany.}, Pages = {167-76}, Pubmed = {9717181}, Title = {Dynamics of microglial activation in the spinal cord after cerebral infarction are revealed by expression of MHC class II antigen}, Uuid = {FF3A72A7-8166-4BE6-92FA-9273568CD365}, Volume = {24}, Year = {1998}} @book{Schmitt:1979, Abstract = {79112912 Francis O. Schmitt and Frederic G. Worden, editors-in-chief ; associate editors, George Adelman, Barry H. Smith ; contributing editors, Floyd E. Bloom ... [et al.]. ill. ; 29 cm. Based on the NRP conference held at the University of Colorado, Boulder, 20 June-1 July, 1977.}, Author = {Schmitt, Francis Otto and Worden, Frederic G. and Neurosciences Research Program.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Isbn = {0262191628}, Keywords = {Neural circuitry Congresses.;M QP376 .N49 591.1/88;Brain Congresses.;Neurology Congresses.;Neural transmission Congresses.}, Publisher = {MIT Press}, Title = {The Neurosciences : fourth study program}, Uuid = {FC570B06-9C8D-4C93-9EA3-85DD7817A84E}, Year = {1979}} @article{Schmitz:2001, Abstract = {We provide physiological, pharmacological, and structural evidence that axons of hippocampal principal cells are electrically coupled, with prepotentials or spikelets forming the physiological substrate of electrical coupling as observed in cell somata. Antidromic activation of neighboring axons induced somatic spikelet potentials in neurons of CA3, CA1, and dentate gyrus areas of rat hippocampal slices. Somatic invasion by these spikelets was dependent on the activation of fast Na(+) channels in the postjunctional neuron. Antidromically elicited spikelets were suppressed by gap junction blockers and low intracellular pH. Paired axo-somatic and somato-dendritic recordings revealed that the coupling potentials appeared in the axon before invading the soma and the dendrite. Using confocal laser scanning microscopy we found that putative axons of principal cells were dye coupled. Our data thus suggest that hippocampal neurons are coupled by axo-axonal junctions, providing a novel mechanism for very fast electrical communication.}, Author = {Schmitz, D. and Schuchmann, S. and Fisahn, A. and Draguhn, A. and Buhl, E. H. and Petrasch-Parwez, E. and Dermietzel, R. and Heinemann, U. and Traub, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Excitatory Amino Acid Antagonists;Fluorescent Dyes;Animals;Evoked Potentials;Rats;Anti-Ulcer Agents;Synaptic Transmission;Female;Axons;Cell Communication;Hippocampus;Pyramidal Cells;Rats, Wistar;Gap Junctions;research support, non-u.s. gov't;Time Factors;Tetrodotoxin;Male;Action Potentials;21 Neurophysiology;GABA Antagonists;21 Gap junctions;Carbenoxolone}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Institute of Physiology, Charit{\'e}, Humboldt-University Berlin, Tucholskystr. 2, 10117, Berlin, Germany. schmitz\@cmp.ucsf.edu}, Pages = {831-40}, Pii = {S0896-6273(01)00410-X}, Pubmed = {11567620}, Title = {Axo-axonal coupling. a novel mechanism for ultrafast neuronal communication}, Uuid = {5AE3D638-E32D-4321-A5C1-6F39C5F7E1A9}, Volume = {31}, Year = {2001}, url = {papers/Schmitz_Neuron2001.pdf}} @article{Schneider:2005, Abstract = {G-CSF is a potent hematopoietic factor that enhances survival and drives differentiation of myeloid lineage cells, resulting in the generation of neutrophilic granulocytes. Here, we show that G-CSF passes the intact blood-brain barrier and reduces infarct volume in 2 different rat models of acute stroke. G-CSF displays strong antiapoptotic activity in mature neurons and activates multiple cell survival pathways. Both G-CSF and its receptor are widely expressed by neurons in the CNS, and their expression is induced by ischemia, which suggests an autocrine protective signaling mechanism. Surprisingly, the G-CSF receptor was also expressed by adult neural stem cells, and G-CSF induced neuronal differentiation in vitro. G-CSF markedly improved long-term behavioral outcome after cortical ischemia, while stimulating neural progenitor response in vivo, providing a link to functional recovery. Thus, G-CSF is an endogenous ligand in the CNS that has a dual activity beneficial both in counteracting acute neuronal degeneration and contributing to long-term plasticity after cerebral ischemia. We therefore propose G-CSF as a potential new drug for stroke and neurodegenerative diseases.}, Author = {Schneider, and Kr{\"u}ger, and Steigleder, and Weber, and Pitzer, and Laage, and Aronowski, and Maurer, and Gassler, and Mier, and Hasselblatt, and Kollmar, and Schwab, and Sommer, and Bach, and Kuhn, and Sch{\"a}bitz,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0021-9738}, Journal = {J Clin Invest}, Keywords = {24 Pubmed search results 2008}, Month = {7}, Nlm_Id = {7802877}, Organization = {Axaron Bioscience AG, Heidelberg, Germany.}, Pubmed = {16007267}, Title = {The hematopoietic factor G-CSF is a neuronal ligand that counteracts programmed cell death and drives neurogenesis}, Uuid = {AD55CC30-8B48-4419-8DDF-15077B378705}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1172/JCI23559}} @article{Schneidman:2006, Abstract = {Biological networks have so many possible states that exhaustive sampling is impossible. Successful analysis thus depends on simplifying hypotheses, but experiments on many systems hint that complicated, higher-order interactions among large groups of elements have an important role. Here we show, in the vertebrate retina, that weak correlations between pairs of neurons coexist with strongly collective behaviour in the responses of ten or more neurons. We find that this collective behaviour is described quantitatively by models that capture the observed pairwise correlations but assume no higher-order interactions. These maximum entropy models are equivalent to Ising models, and predict that larger networks are completely dominated by correlation effects. This suggests that the neural code has associative or error-correcting properties, and we provide preliminary evidence for such behaviour. As a first test for the generality of these ideas, we show that similar results are obtained from networks of cultured cortical neurons.}, Author = {Schneidman, Elad and Berry, Michael J. and Segev, Ronen and Bialek, William}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Retina;Poisson Distribution;research support, non-u.s. gov't;Action Potentials;Entropy;Guinea Pigs;Models, Neurological;Urodela;research support, n.i.h., extramural;Animals;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Mid = {NIHMS11415}, Month = {4}, Nlm_Id = {0410462}, Number = {7087}, Organization = {Joseph Henry Laboratories of Physics, Princeton University, Princeton, New Jersey 08544, USA. elads\@princeton.edu}, Pages = {1007-12}, Pii = {nature04701}, Pmc = {PMC1785327}, Pubmed = {16625187}, Title = {Weak pairwise correlations imply strongly correlated network states in a neural population}, Uuid = {DB5414D0-4E0E-422D-9258-551EC4E40A8D}, Volume = {440}, Year = {2006}, url = {papers/Schneidman_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04701}} @article{Schnitzer:2003, Abstract = {Population codes in the brain have generally been characterized by recording responses from one neuron at a time. This approach will miss codes that rely on concerted patterns of action potentials from many cells. Here we analyze visual signaling in populations of ganglion cells recorded from the isolated salamander retina. These neurons tend to fire synchronously far more frequently than expected by chance. We present an efficient algorithm to identify what groups of cells cooperate in this way. Such groups can include up to seven or more neurons and may account for more than 50\%of all the spikes recorded from the retina. These firing patterns represent specific messages about the visual stimulus that differ significantly from what one would derive by single-cell analysis.}, Author = {Schnitzer, Mark J. and Meister, Markus}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:31 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Visual Cortex;Photic Stimulation;research support, non-u.s. gov't;21 Neurophysiology;Action Potentials;Algorithms;Models, Neurological;Urodela;Retinal Ganglion Cells;research support, u.s. gov't, p.h.s.;Animals;Visual Pathways;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Biological Computation and Theoretical Physics Research Department, Bell Laboratories, Lucent Technologies, Murray Hill, NJ 07974, USA.}, Pages = {499-511}, Pii = {S0896627303000047}, Pubmed = {12575956}, Title = {Multineuronal firing patterns in the signal from eye to brain}, Uuid = {3F77227F-5011-49CD-A615-4D1E5CFFC735}, Volume = {37}, Year = {2003}, url = {papers/Schnitzer_Neuron2003.pdf}} @article{Schoen:1992, Abstract = {The ecto-enzyme 5'-nucleotidase was localized immunocytochemically in the axotomized rat facial nucleus. As revealed by the monoclonal antibody 5N4-2,5'-nucleotidase immunoreactivity markedly increased on perineuronal microglia during the first week following axotomy, and gradually disappeared from these cells by the end of the third post-operative week. Interestingly, parenchymal microglia were not or only weakly stained. These findings indicate that 5'-nucleotidase 5N4-2-immunoreactivity may serve as a marker for perineuronal microglia, a population of satellite glial cells that appear to be actively engaged in lesion-induced synaptic changes during regeneration.}, Author = {Schoen, S. W. and Graeber, M. B. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Tissue Distribution;Neuroglia;Facial Nerve;Rats;Immunohistochemistry;Time Factors;Denervation;Rats, Wistar;11 Glia;5'-Nucleotidase;Animals;Axons}, Medline = {93100085}, Nlm_Id = {8806785}, Number = {4}, Organization = {Department of Neuromorphology, Max-Planck-Institute of Psychiatry, Martinsried, Germany.}, Pages = {314-7}, Pubmed = {1464463}, Title = {5'-Nucleotidase immunoreactivity of perineuronal microglia responding to rat facial nerve axotomy}, Uuid = {FE4A258C-BB28-4B3F-939C-0B990038BEA1}, Volume = {6}, Year = {1992}} @article{Schools:2003, Abstract = {We have recently described a subgroup of isolated glial fibrillary acidic protein-positive (GFAP+) hippocampal astrocytes that predominantly express outwardly rectifying currents (which we term "ORAs"for outwardly rectifying astrocytes), which are similar to the currents already described for hippocampal GFAP- "complex glia."We now report that post-recording staining of cells that were first selected as "complex"by morphology and then confirmed by their electrophysiological characteristics were NG2+ approximately 90\%of the time. Also, the morphology of freshly isolated NG2+ cells differs from that of isolated GFAP+ ORAs in having a smaller and round cell body with thinner processes, which usually are collapsed back onto the soma. Upon detailed examination, NG2+ cells were found to differ quantitatively in some electrophysiological characteristics from GFAP+ ORAs. The outward, transient K+ currents (IKa) in the NG2+ cells showed a slower decay than the IKa in ORAs, and their density decreased in NG2+ cells from older animals. The other two major cation currents, the voltage-activated Na+ and outwardly delayed rectifier K+ currents, were similar in NG2+ cells and ORAs. To further distinguish isolated complex cells from outwardly rectifying GFAP+ astrocytes, we performed immunocytochemistry for glial markers in fixed, freshly isolated rat hippocampal glia. NG2+ cells were negative for GFAP and also for the astrocytic glutamate transporters GLT-1 and GLAST. Thus the isolated hippocampal NG2+ glial cells, though having an electrophysiological phenotype similar to that of ORAs, are an immunologically and morphologically distinct glial cell population and most likely represent NG2+ cells in situ. 0360-4012 Journal Article}, Author = {Schools, G. P. and Zhou, M. and Kimelberg, H. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci Res}, Keywords = {Animals;Electric Conductivity;Cells, Cultured;Rats;Comparative Study;Immunohistochemistry/methods;Cell Count;Patch-Clamp Techniques/*methods;11 Glia;Time Factors;Antigens/*analysis/immunology;Proteoglycans/*analysis/immunology;Animals, Newborn;Glial Fibrillary Acidic Protein/immunology;Amino Acid Transport System X-AG/metabolism;Anesthetics, Local/pharmacology;Tetrodotoxin/pharmacology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;G pdf;Hippocampus/*cytology/metabolism;Neuroglia/classification/drug effects/*metabolism/physiology}, Number = {6}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.}, Pages = {765-77}, Pubmed = {12949902}, Title = {Electrophysiologically "complex"glial cells freshly isolated from the hippocampus are immunopositive for the chondroitin sulfate proteoglycan NG2}, Uuid = {63CF07C2-5187-4BC2-A060-DD58BAFCD2E5}, Volume = {73}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12949902}} @article{Schoppa:2006, Abstract = {Gamma frequency (30-70 Hz) synchronized oscillatory activity in the olfactory bulb is widely believed to be important for odor detection and discrimination. As in other circuits with "gamma activity," the activity in the bulb is driven by GABAergic interneurons, specifically a class of axonless cells called granule cells. However, bulb granule cells appear to lack some key mechanistic features that promote rapid synchrony in other circuits, including direct electrical interconnections and dominant actions for fast neurotransmitter receptors. At least under "static" stimulus conditions, granule cells are driven by kinetically slow NMDA receptors. Here, I used patch-clamp recordings in rat olfactory bulb slices to better understand mechanisms that shape granule cell activity under "dynamic" stimulus conditions that mimic a natural odor stimulus. During a 4 Hz patterned stimulation of olfactory nerve afferents, activation of single granule cells was primarily controlled by two classes of AMPA/kainate receptor-mediated synaptic inputs derived from output mitral cells. The rapid kinetics of these receptors, together with inactivation of A-type potassium channels, ensured that granule cells had short spike-response times. Studies in cell pairs, moreover, indicated that excitatory inputs could synchronize granule cells on a rapid time scale (2-5 ms), in turn resulting in phase-locked GABA release onto mitral cells. The precision of granule cell synchrony was controlled by the same biophysical mechanisms that promoted rapid single-cell spiking. These studies demonstrate the mechanistic underpinnings that transform a circuit with slow, uncoupled activity under static conditions into a fast, dynamic circuit operating with high precision under physiological conditions.}, Author = {Schoppa, Nathan E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Rats, Sprague-Dawley;21 Neurophysiology;Action Potentials;Rats;Receptors, AMPA;Receptors, Kainic Acid;comparative study;research support, n.i.h., extramural;Olfactory Bulb;Animals;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8102140}, Number = {50}, Organization = {Department of Physiology and Biophysics, University of Colorado at Denver Health Sciences Center at Fitzsimons, Aurora, Colorado 80045, USA. Nathan.Schoppa\@UCHSC.edu}, Pages = {12996-3006}, Pii = {26/50/12996}, Pubmed = {17167089}, Title = {AMPA/kainate receptors drive rapid output and precise synchrony in olfactory bulb granule cells}, Uuid = {8ECD9C94-1DC9-48A4-9754-A578CC504C25}, Volume = {26}, Year = {2006}, url = {papers/Schoppa_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3503-06.2006}} @article{Schoppa:2001, Abstract = {Odor elicits a well-organized pattern of glomerular activation in the olfactory bulb. However, the mechanisms by which this spatial map is transformed into an odor code remain unclear. We examined this question in rat olfactory bulb slices in recordings from output mitral cells. Electrical stimulation of incoming afferents elicited slow ( approximately 2 Hz) oscillations that originated in glomeruli and were highly synchronized for mitral cells projecting to the same glomerulus. Cyclical depolarizations were generated by glutamate activation of dendritic autoreceptors, while the slow frequency was determined primarily by the duration of regenerative glutamate release. Patterned stimuli elicited stimulus-entrained oscillations that amplified weak and variable inputs. We suggest that these oscillations maintain the fidelity of the spatial map by ensuring that all mitral cells within a glomerulus-specific network respond to odor as a functional unit.}, Author = {Schoppa, N. E. and Westbrook, G. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Neuron}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {4}, Organization = {Vollum Institute, Oregon Health Sciences University, 97201, Portland, OR, USA}, Pages = {639-51.}, Title = {Glomerulus-specific synchronization of mitral cells in the olfactory bulb}, Uuid = {0FE6D59D-A552-4F2D-89E2-58F91703217C}, Volume = {31}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11545722}} @article{Schottler:1998, Abstract = {Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.}, Author = {Schottler, F. and Couture, D. and Rao, A. and Kahn, H. and Lee, K. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {24 Pubmed search results 2008;Motor Cortex;Rats;Dextrans;Research Support, U.S. Gov't, P.H.S.;Efferent Pathways;Fluorescent Dyes;Rats, Mutant Strains;Neural Pathways;Biotin;Brain Mapping;Somatosensory Cortex;Thalamus;Afferent Pathways;Animals;Neurons;Microinjections}, Medline = {98250426}, Month = {5}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Neurological Surgery, Health Sciences Center, University of Virginia, Charlottesville 22908, USA.}, Pages = {29-42}, Pii = {10.1002/(SICI)1096-9861(19980525)395:1<29::AID-CNE3>3.0.CO;2-J}, Pubmed = {9590544}, Title = {Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat}, Uuid = {D15C3349-5695-45E1-B7E9-C1DCF3F96AD8}, Volume = {395}, Year = {1998}, url = {papers/Schottler_JCompNeurol1998.pdf}} @article{Schottler:2001, Abstract = {The tish rat is a neurological mutant exhibiting bilateral cortical heterotopia similar to those found in certain epileptic patients. Previous work has shown that thalamocortical fibers originating in the ventroposteromedial nucleus, which in normal animals segregate as 'barrel' representations for individual whiskers, terminate in both normotopic and heterotopic areas of the tish cortex (Schottler et al., 1998). Thalamocortical innervation terminates as barrels in layer IV and diffusely in layer VI of the normotopic area. Discrete patches of terminals are also observed in the underlying heterotopic area suggesting that representations of individual vibrissa may be present in the heterotopic somatosensory areas. The present study examines this issue by investigating the organization of the vibrissal somatosensory system in the tish cortex. Staining for cytochrome oxidase or Nissl substance reveals a normal complement of vibrissal barrels in the normotopic area of the tish cortex. Dense patches of cytochrome oxidase staining are also found in the underlying lateral portions of the heterotopic area (i.e. the same area that is innervated by the ventroposteromedial nucleus). Injections of retrograde tracers into vibrissal areas of either the normotopic or heterotopic area produce topographically organized labeling of neurons restricted to one or a small number of barreloids within the ventroposteromedial nucleus of the thalamus. Physical stimulation of a single whisker (D3 or E3) elicits enhanced uptake of [(14)C]2-deoxyglucose in restricted zones of both the normotopic and heterotopic areas, demonstrating that single whisker stimulation can increase functional activity in both normotopic and heterotopic neurons. These findings indicate that the barrels are intact in the normotopic area and are most consistent with the hypothesis that at least some of the individual vibrissae are 'dually' represented in normotopic and heterotopic positions in the primary somatosensory areas of the tish cortex.}, Author = {Schottler, F. and Fabiato, H. and Leland, J. M. and Chang, L. Y. and Lotfi, P. and Getachew, F. and Lee, K. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Animals;Gene Expression Regulation, Developmental;Rats;Ventral Thalamic Nuclei;Neural Pathways;Epilepsy;Rats, Sprague-Dawley;Vibrissae;21 Dysplasia-heterotopia;Organ Culture Techniques;Deoxyglucose;Research Support, U.S. Gov't, P.H.S.;Nervous System Malformations;Evoked Potentials, Somatosensory;21 Neurophysiology;Neurons;Electron Transport Complex IV;Somatosensory Cortex;Body Patterning;24 Pubmed search results 2008;Choristoma;Rats, Mutant Strains}, Medline = {21592848}, Nlm_Id = {7605074}, Number = {2}, Organization = {Department of Neuroscience, University of Virginia, Box 801392, MR4 Annex, Charlottesville, VA 22098, USA.}, Pages = {217-35}, Pii = {S0306-4522(01)00395-5}, Pubmed = {11734356}, Title = {Normotopic and heterotopic cortical representations of mystacial vibrissae in rats with subcortical band heterotopia}, Uuid = {F13F6998-638B-4249-B147-D6F61ADF4802}, Volume = {108}, Year = {2001}, url = {papers/Schottler_Neuroscience2001.pdf}} @article{Schratt:2004, Abstract = {Local regulation of mRNA translation plays an important role in axon guidance, synaptic development, and neuronal plasticity. Little is known, however, regarding the mechanisms that control translation in neurons, and only a few mRNAs have been identified that are locally translated within axon and dendrites. Using Affymetrix gene arrays to identify mRNAs that are newly associated with polysomes after exposure to BDNF, we identified subsets of mRNAs for which translation is enhanced in neurons at different developmental stages. In mature neurons, many of these mRNAs encode proteins that are known to function at synapses, including CamKIIalpha, NMDA receptor subunits, and the postsynaptic density (PSD) scaffolding protein Homer2. BDNF regulates the translation of Homer2 locally in the synaptodendritic compartment by activating translational initiation via a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway. These findings suggest that BDNF likely regulates synaptic function by inducing the local synthesis of numerous synaptic proteins. The local translation of the cytoskeleton-associated protein Homer2 in particular might have important implications for growth cone dynamics and dendritic spine development.}, Author = {Schratt, Gerhard M. and Nigh, Elizabeth A. and Chen, Wen G. and Hu, Linda and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Signal Transduction;Rats, Long-Evans;Animals;Synapses;Carrier Proteins;Rats;Gene Expression Regulation;Brain-Derived Neurotrophic Factor;research support, u.s. gov't, p.h.s. ;Protein Kinases;Brain;RNA, Messenger;Gene Expression Profiling;1-Phosphatidylinositol 3-Kinase;Dendrites;research support, non-u.s. gov't ;Polyribosomes;21 Neurophysiology;Neurons;Protein Biosynthesis;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {33}, Organization = {Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, USA.}, Pages = {7366-77}, Pii = {24/33/9366}, Pubmed = {15317862}, Title = {BDNF regulates the translation of a select group of mRNAs by a mammalian target of rapamycin-phosphatidylinositol 3-kinase-dependent pathway during neuronal development}, Uuid = {DD484147-9A6B-4165-9F10-EF356919B2FC}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1739-04.2004}} @article{Schratt:2006, Abstract = {MicroRNAs are small, non-coding RNAs that control the translation of target messenger RNAs, thereby regulating critical aspects of plant and animal development. In the mammalian nervous system, the spatiotemporal control of mRNA translation has an important role in synaptic development and plasticity. Although a number of microRNAs have been isolated from the mammalian brain, neither the specific microRNAs that regulate synapse function nor their target mRNAs have been identified. Here we show that a brain-specific microRNA, miR-134, is localized to the synapto-dendritic compartment of rat hippocampal neurons and negatively regulates the size of dendritic spines--postsynaptic sites of excitatory synaptic transmission. This effect is mediated by miR-134 inhibition of the translation of an mRNA encoding a protein kinase, Limk1, that controls spine development. Exposure of neurons to extracellular stimuli such as brain-derived neurotrophic factor relieves miR-134 inhibition of Limk1 translation and in this way may contribute to synaptic development, maturation and/or plasticity.}, Author = {Schratt, Gerhard M. and Tuebing, Fabian and Nigh, Elizabeth A. and Kane, Christina G. and Sabatini, Mary E. and Kiebler, Michael and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-13 09:45:17 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Animals;Synapses;Base Sequence;Gene Expression Regulation, Developmental;Rats;Brain-Derived Neurotrophic Factor;Protein Kinases;Brain;Dendritic Spines;MicroRNAs;Hippocampus;RNA, Messenger;research support, non-u.s. gov't ;Organ Specificity;21 Neurophysiology;Cell Shape;Protein Biosynthesis;24 Pubmed search results 2008; microRNAs; development}, Month = {1}, Nlm_Id = {0410462}, Number = {7074}, Organization = {Neurobiology Program, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {283-9}, Pii = {nature04367}, Pubmed = {16421561}, Title = {A brain-specific microRNA regulates dendritic spine development}, Uuid = {412C3AB6-A1A6-462D-B694-5B993C25A6C4}, Volume = {439}, Year = {2006}, url = {papers/Schratt_Nature2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04367}} @article{Schroeter:2001, Abstract = {We have recently described a novel population of CD8+ phagocytes that are strongly recruited to focal ischemic lesions of the rat brain but absent from axotomized central fiber tracts. To assess the relative contribution of infiltrating macrophages and resident microglia to the CD8+ phagocyte response, we selectively depleted peripheral macrophages by systemic administration of dichloromethylene diphosphonate-filled liposomes prior to the induction of permanent ischemia by photothrombosis of cortical microvessels. Macrophage depletion led to a dramatic reduction but not complete abolishment of CD8+ cells in the ensuing infarcts. Systemic administration of monoclonal antibody Ox-8 eliminated CD8+ cells from peripheral lymphoid organs but had no effect on CD8+ phagocytes in the ischemic brain lesions. To further characterize the lesion conditions inducing the recruitment of CD8+ phagocytes, we induced mild focal ischemia by transient occlusion of the middle cerebral artery that leads to a core infarction with ischemic pannecrosis surrounded by areas with selective neuronal cell death. Recruitment of CD8+ phagocytes was restricted to areas of ischemic pannecrosis. In areas undergoing selective neuronal loss microglia up-regulated complement receptor-3, exhibited ED1 immunoreactivity (indicating phagocytic activity), and to some extent expressed CD4, but not CD8 antigens. In conclusion our present study shows that CD8+ phagocytes in focal brain ischemia are predominantly derived from hematogenous macrophages and selectively target to areas of ischemic pannecrosis.}, Author = {Schroeter, M. and Jander, S. and Huitinga, I. and Stoll, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0001-6322}, Journal = {Acta Neuropathol (Berl)}, Keywords = {Phagocytosis;Animals;Macrophages;Rats;Infarction, Middle Cerebral Artery;Lymphocytes;Microglia;Antigens, CD4;Macrophage Activation;Not relevant;Phagocytes;Rats, Wistar;11 Glia;Support, Non-U.S. Gov't;Membrane Glycoproteins;Antigens, CD8;Brain Ischemia;Immunohistochemistry;Membrane Proteins;Necrosis;Clodronic Acid;Glial Fibrillary Acidic Protein}, Medline = {21377043}, Month = {5}, Nlm_Id = {0412041}, Number = {5}, Organization = {Department of Neurology and Center for Biological and Medical Research, Heinrich-Heine-University, D{\"u}sseldorf, Germany.}, Pages = {440-8}, Pubmed = {11484815}, Title = {CD8+ phagocytes in focal ischemia of the rat brain: predominant origin from hematogenous macrophages and targeting to areas of pannecrosis}, Uuid = {4DC17467-5FBA-483D-8494-CDB7DEEFAD99}, Volume = {101}, Year = {2001}} @article{Schuetz:2004, Abstract = {Retinal ganglion cells (RGCs) regenerating through peripheral nerve grafts show enhanced survival after further axonal injury for at least 4 weeks [Restor. Neurol. Neurosci. 21 (2003) 11]. Here, we examined the survival of the neurons and their microglial phagocytosis in dependence of the site of reaxotomy. Therefore, the optic nerve in adult rats was transected at different distances from the eye cup and replaced with an autologous piece of sciatic nerve. After 14 days of axonal growth, the regenerated neurites were reaxotomized either within the remaining optic stump or within the graft and their cell bodies were retrogradely labeled. Reaxotomy of regenerated ganglion cells within the remaining optic nerve resulted in reduced (but not significant) ganglion cell survival and significant microglial phagocytosis in contrast to reaxotomy within the peripheral nerve graft. Furthermore, phagocytosis-dependent labeling using two different fluorescent tracers revealed that the same microglial cell can phagocytose further dying ganglion cells within 14 days after the first activation. The results suggest that the intrasciatic segments of axons receive some trophic support that is retrogradely transported and required to limit the microglial activation. The microglial capability to phagocytose dying neurons several fold emphasizes their function in permanent scavenging within the retina.}, Author = {Schuetz, Erik and Thanos, Solon}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0361-9230}, Journal = {Brain Res Bull}, Keywords = {Retina;Sciatic Nerve;Rats, Sprague-Dawley;Nerve Regeneration;Cell Communication;Female;Rats;Not relevant;11 Glia;Microglia;Retinal Ganglion Cells;Optic Nerve;Axotomy;Animals;Support, Non-U.S. Gov't;Male;Phagocytosis}, Medline = {23341186}, Month = {2}, Nlm_Id = {7605818}, Number = {5}, Organization = {Department of Experimental Ophthalmology, University Eye Hospital M{\"u}nster, Domagkstrasse 15, 48149 M{\"u}nster, Germany.}, Pages = {391-6}, Pii = {S0361923003002995}, Pubmed = {15168904}, Title = {Neuro-glial interactions in the adult rat retina after reaxotomy of ganglion cells: examination of neuron survival and phagocytic microglia using fluorescent tracers}, Uuid = {FA7FA605-F5D4-4E5C-90E6-AE000FE6F122}, Volume = {62}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainresbull.2003.10.008}} @article{Schulz:1995, Abstract = {Recent evidence has linked excitotoxicity with the generation of free radicals. We examined whether free radical spin traps can attenuate excitotoxic lesions in vivo. Pretreatment with N-tert-butyl-alpha-(2- sulfophenyl)-nitrone (S-PBN) significantly attenuated striatal excitotoxic lesions in rats produced by N-methyl-D-aspartate (NMDA), kainic acid, and alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA). In a similar manner, striatal lesions produced by 1-methyl- 4-phenylpyridinium (MPP+), malonate, and 3-acetylpyridine were significantly attenuated by either S-PBN or alpha-phenyl-N-tert- butylnitrone (PBN) treatment. Administration of S-PBN in combination with the NMDA antagonist MK-801 produced additive effects against malonate and 3-acetylpyridine toxicity. Malonate injections resulted in increased production of hydroxyl free radicals (.OH) as assessed by the conversion of salicylate to 2,3- and 2,5-dihydroxybenzoic acid (DHBA). This increase was significantly attenuated by S-PBN, consistent with a free radical scavenging effect. S-PBN had no effects on malonate- induced ATP depletions and had no significant effect on spontaneous striatal electrophysiologic activity. These results provide the first direct in vivo evidence for the involvement of free radicals in excitotoxicity and suggest that antioxidants may be useful in treating neurologic illnesses in which excitotoxic mechanisms have been implicated.}, Author = {Schulz, J. B. and Henshaw, D. R. and Siwek, D. and Jenkins, B. G. and Ferrante, R. J. and Cipolloni, P. B. and Kowall, N. W. and Rosen, B. R. and Beal, M. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurochem}, Keywords = {N-Methylaspartate/*pharmacology;E-3;Dizocilpine Maleate/pharmacology;Electrophysiology;Kainic Acid/pharmacology;Rats;Cells, Cultured;07 Excitotoxicity Apoptosis;Animal;Free Radicals;Rats, Sprague-Dawley;Male;Support, Non-U.S. Gov't;Brain/*drug effects/physiology;Receptors, Glutamate/drug effects/*physiology;Support, U.S. Gov't, P.H.S.;Cell Death/drug effects;Hydroxyl Radical/metabolism;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology;Nitrogen Oxides/pharmacology;Neurons/*drug effects/physiology;Free Radical Scavengers/*pharmacology}, Number = {5}, Organization = {Neurochemistry Laboratory, Massachusetts General Hospital 02114, USA.}, Pages = {2239-47.}, Title = {Involvement of free radicals in excitotoxicity in vivo}, Uuid = {C75B07A9-9154-4186-A9C1-A0F124785D9E}, Volume = {64}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7536809}} @article{Schumann:1979, Author = {Schumann, G. and Gisler, R. H. and Brownbill, A. F. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0065-2598}, Journal = {Adv Exp Med Biol}, Keywords = {15 ERVs retroelements;Spleen;Mice;Mice, Inbred BALB C;Cytotoxicity, Immunologic;B-Lymphocytes;24 Pubmed search results 2008;Retroviridae;T-Lymphocytes;Immunosuppression;Macrophages;15 Retrovirus mechanism;Animals;Lymphocyte Culture Test, Mixed;Hemolytic Plaque Technique;Antibodies, Viral;Immune Sera}, Medline = {79228515}, Nlm_Id = {0121103}, Pages = {233-7}, Pubmed = {223415}, Title = {Are endogenous C-type viruses physiologically required for the regulation of the humoral immune response?}, Uuid = {2CC70E17-A78C-425D-BE8F-9A5A4ABEDBB4}, Volume = {114}, Year = {1979}} @article{Schumann:1976, Abstract = {We reported previously in vitro induction of endogenous C-type viruses from normal mouse spleen cells by lipopolysaccharide (LPS) as well as by combination treatment with concanabalin A and 5-bromo-2'-deoxyuridine (Con A/BrdU). To identify the cell types sensitive to virus induction and to study the relationship of mitogenicity to virus induction we have compared T cell populations (BALB/c thymus cells and cortisone-resistant thymus cells), B cell populations (nu/nu spleen cells and lymph node cells), adherent BALB/c peritoneal cells and mixed populations (BALB/c spleen cells, macrophage-depleted BALB/c spleen cells, and lymph node cells). LPS-induction occurred only in B cell-containing populations. In contrast, induction by Con A/BrdU depended on the presence of both T and B cells. In both instances, neither macrophages nor hemopoietic cells appeared to be a major source of virus. Treatment with anti-Ig serum and complement reduced virus induction by LPS/BrdU but not by Con A/BrdU suggesting that different cell populations produce virus after stimulation with these two different mitogens.}, Author = {Schumann, G. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {Complement System Proteins;T-Lymphocytes;Mice, Inbred BALB C;Animals;Macrophages;Antibodies, Anti-Idiotypic;Lipopolysaccharides;15 Retrovirus mechanism;Lymph Nodes;B-Lymphocytes;Retroviridae;Mitogens;Concanavalin A;Mice, Nude;Mice;24 Pubmed search results 2008;15 ERVs retroelements;Spleen}, Medline = {76144682}, Month = {4}, Nlm_Id = {2985117R}, Number = {4}, Pages = {1145-50}, Pubmed = {176274}, Title = {Mitogen induction of murine C-type viruses. I. Analysis of lymphoid cell subpopulations}, Uuid = {A5CB72FF-F4B7-45C0-81EE-919AE94C342A}, Volume = {116}, Year = {1976}} @article{Schumann:1978, Abstract = {We have analyzed the effects of an antiserum prepared against BALB/c endogenous xenotropic C-type virus on the humoral immune response of mice. Both in vivo and in vitro, this serum suppresses the response to sheep red blood cells, an effect that can be absorbed out by purified BALB/c xenotropic C-type virus or Friend leukemia virus, but not by Rous sarcoma virus. The serum produces its maximum effect when administered together with or before the antigen, but not 24 hr later. This suggests that it acts on an early event of the immune response. Evidence is presented to show that the critical viral antigen is expressed before the spleen cells are experimentally stimulated by antigen. The same immunosuppressive effect was observed in a variety of mouse strains, including the high-leukemia incidence AKR strain and virus-free 129/J mice, indicating that it is independent of the expression of endogenous virus. The finding that a viral antigen is involved in the transition from a resting to a dividing lymphocyte is discussed with respect to viral involvement in leukemia.}, Author = {Schumann, G. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {15 ERVs retroelements;Immune Sera;Mice, Inbred AKR;Mice, Inbred BALB C;Mice, Inbred DBA;Retroviridae;Mice, Inbred C57BL;Time Factors;Immunosuppression;15 Retrovirus mechanism;Animals;Mice;24 Pubmed search results 2008;Hemolytic Plaque Technique;Antigen-Antibody Reactions}, Medline = {78195399}, Month = {6}, Nlm_Id = {2985117R}, Number = {6}, Pages = {1913-6}, Pubmed = {207777}, Title = {Immunosuppressive activity of antibody directed against endogenous C-type virus interferes with early events of the immune response}, Uuid = {5E401B2F-D516-418C-AFA6-B7C5151447E0}, Volume = {120}, Year = {1978}} @article{Schumann:1977, Author = {Schumann, G. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {Dose-Response Relationship, Drug;Drug Synergism;Animals;Gammaretrovirus;DNA;Lipopolysaccharides;Culture Techniques;15 Retrovirus mechanism;Polysaccharides;Lymph Nodes;Retroviridae;Mitogens;Mice, Inbred Strains;Escherichia coli;Age Factors;Genotype;Mice;24 Pubmed search results 2008;Virus Replication;Bromodeoxyuridine;15 ERVs retroelements;Spleen}, Medline = {77197290}, Month = {6}, Nlm_Id = {0110674}, Number = {1}, Pages = {81-7}, Pubmed = {194404}, Title = {Mitogen induction of murine C-type viruses. III. Effect of culture conditions, age, and genotype}, Uuid = {9528DBF0-BC35-415E-800E-D93ED736E9AA}, Volume = {79}, Year = {1977}} @article{Schwab:1998, Abstract = {Basic helix-loop-helix (bHLH) genes have emerged as important regulators of neuronal determination and differentiation in vertebrates. Three putative neuronal differentiation factors [NEX for neuronal helix-loop-helix protein-1 (mammalian atonal homolog-2), neuroD (beta-2), and NDRF for neuroD-related factor (neuroD2)] are highly homologous to each other in the bHLH region and comprise a new bHLH subfamily. To study the role of NEX, the first bHLH protein identified in this group, we have disrupted the NEX gene by homologous recombination. NEX-deficient mice have no obvious developmental defect, and CNS neurons appear fully differentiated. To investigate further whether the absence of NEX is compensated for by neuroD and NDRF, we compared the spatiotemporal expression of all three genes. We demonstrate, by in situ hybridization, that the transcription patterns of NEX, neuroD, and NDRF genes are highly overlapping in the developing CNS of normal rats between embryonic day 12 and adult stages but are not strictly identical. The most prominent transcription of each gene marks the dorsal neuroepithelium of the telencephalon in early development and is sustained in the adult neocortex, hippocampus, and cerebellum. In general, neuroD provides the earliest marker of neuronal differentiation in any given region compared with NDRF or NEX. Whereas a few CNS regions are specific for neuroD, no region was detected in which solely NEX or NDRF is expressed. This suggests that the function of the mutant NEX gene in neuronal differentiation is compensated for by neuroD and NDRF and that, in analogy with myogenic bHLH proteins, neuronal differentiation factors are at least in part equivalent in function.}, Author = {Schwab, M. H. and Druffel-Augustin, S. and Gass, P. and Jung, M. and Klugmann, M. and Bartholomae, A. and Rossner, M. J. and Nave, K. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Aging;Cell Differentiation;Rats, Sprague-Dawley;Research Support, Non-U.S. Gov't;Embryonic and Fetal Development;Helix-Loop-Helix Motifs;Rats;Nerve Tissue Proteins;Neuropeptides;Gene Expression;Mice, Transgenic;Animals, Newborn;Mice;Brain;Animals;Neurons}, Medline = {98122897}, Month = {2}, Nlm_Id = {8102140}, Number = {4}, Organization = {Zentrum f{\"u}r Molekulare Biologie (ZMBH), University of Heidelberg, D-69120 Heidelberg, Germany.}, Pages = {1408-18}, Pubmed = {9454850}, Title = {Neuronal basic helix-loop-helix proteins (NEX, neuroD, NDRF): spatiotemporal expression and targeted disruption of the NEX gene in transgenic mice}, Uuid = {AD8B2456-A3E5-11DA-AB00-000D9346EC2A}, Volume = {18}, Year = {1998}, url = {papers/Schwab_JNeurosci1998.pdf}} @article{Schwab:2000, Abstract = {The transcription factors neuronal helix-loop-helix protein (NEX)/mammalian atonal homolog 2 (Math-2), BETA2/neuronal determination factor (NeuroD), and NeuroD-related factor (NDRF)/NeuroD2 comprise a family of Drosophila atonal-related basic helix-loop-helix (bHLH) proteins with highly overlapping expression in the developing forebrain. The ability of BETA2/NeuroD and NDRF to convert ectodermal cells into neurons after mRNA injection into Xenopus oocytes suggested a role in specifying neuronal cell fate. However, neuronal bHLH genes are largely transcribed in CNS neurons, which are fully committed. Here we analyze a defect in mice lacking BETA2/NeuroD, and in NEX*BETA2/NeuroD double mutants, demonstrating that bHLH proteins are required in vivo for terminal neuronal differentiation. Most strikingly, presumptive granule cells of the dentate gyrus are generated but fail to mature, lack normal sodium currents, and show little dendritic arborization. Long-term hippocampal slice cultures demonstrate secondary alterations of entorhinal and commissural/associational projections. The primary developmental arrest appears to be restricted to granule cells in which an autoregulatory system involving all three neuronal bHLH genes has failed.}, Author = {Schwab, M. H. and Bartholomae, A. and Heimrich, B. and Feldmeyer, D. and Druffel-Augustin, S. and Goebbels, S. and Naya, F. J. and Zhao, S. and Frotscher, M. and Tsai, M. J. and Nave, K. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Trans-Activation (Genetics);Viral Proteins;Cell Differentiation;Animals;Gene Expression Regulation, Developmental;Helix-Loop-Helix Motifs;Apoptosis;Ki-67 Antigen;Integrases;Patch-Clamp Techniques;Cell Adhesion Molecules, Neuronal;Mice, Inbred C57BL;Extracellular Matrix Proteins;Action Potentials;Research Support, U.S. Gov't, P.H.S.;Mice, Knockout;Animals, Newborn;Dentate Gyrus;Neurons;In Situ Nick-End Labeling;Mice;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {20266180}, Month = {5}, Nlm_Id = {8102140}, Number = {10}, Organization = {Zentrum f{\"u}r Molekulare Biologie, University of Heidelberg, D-69120 Heidelberg, Germany.}, Pages = {3714-24}, Pii = {20/10/3714}, Pubmed = {10804213}, Title = {Neuronal basic helix-loop-helix proteins (NEX and BETA2/Neuro D) regulate terminal granule cell differentiation in the hippocampus}, Uuid = {08B5407B-716F-11DA-A383-000D9346EC2A}, Volume = {20}, Year = {2000}, url = {papers/Schwab_JNeurosci2000.pdf}} @article{Schwartz:2005, Abstract = {The failure of the spinal cord to recover after injury has been associated with the immune privilege mechanism that suppresses immune activity throughout the central nervous system. Primed macrophages and dendritic cells were shown to promote neurological recovery in preclinical models of spinal cord injury. A cell therapy consisting of autologous incubated macrophages is now being tested on spinal cord injury patients in clinical trials.}, Author = {Schwartz, M. and Yoles, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0065-1419}, Journal = {Acta Neurochir Suppl}, Keywords = {Treatment Outcome;Spinal Cord Injuries;Nerve Regeneration;Rats;Recovery of Function;11 Glia;Research;review, tutorial;Macrophages;Dendritic Cells;Humans;Clinical Trials;Pilot Projects;review;Animals}, Medline = {102323079}, Nlm_Id = {100962752}, Organization = {Department Neurophysiology, Weizmann Institute of Science, Rehovot, Israel.}, Pages = {147-50}, Pubmed = {15986745}, Title = {Macrophages and dendritic cells treatment of spinal cord injury: from the bench to the clinic}, Uuid = {B0A23399-4FBF-4CBD-B1C0-30619DB343CD}, Volume = {93}, Year = {2005}} @article{Schwartz:1974, Author = {Schwartz, S. A. and Panem, S. and Stefanski, E. and Kirsten, W. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0008-5472}, Journal = {Cancer Res}, Keywords = {Tritium;Antigens, Viral;Animals;Cells, Cultured;Rats;Fluorescent Antibody Technique;Centrifugation, Density Gradient;15 Retrovirus mechanism;Uridine;Retroviridae;Time Factors;Rats, Inbred WF;Embryo;Animals, Newborn;DNA Nucleotidyltransferases;Mice;24 Pubmed search results 2008;Microscopy, Electron;Bromodeoxyuridine;15 ERVs retroelements;Neoplasms, Experimental;Cell Transformation, Neoplastic}, Medline = {74278198}, Month = {9}, Nlm_Id = {2984705R}, Number = {9}, Pages = {2255-9}, Pubmed = {4367286}, Title = {Endogenous type C particles from rat embryo cells treated with 5-bromodeoxyuridine}, Uuid = {8DFFB0F6-4328-11DB-A5D2-000D9346EC2A}, Volume = {34}, Year = {1974}} @article{Schwartz:1998, Abstract = {Spontaneous neuronal activity plays an important role in the development of cortical circuitry, yet its spatio-temporal dynamics are poorly understood. Cajal-Retzius (CR) neurons in developing layer 1 are necessary for correct cortical lamination and are strategically located to coordinate early circuit activity. To characterize the spontaneous activity of CR and other layer 1 neurons during cortical development, we imaged calcium transients in populations of layer 1 neurons in hemispheres and slices from postnatal rat somato-sensory neocortex. The spontaneous activity in layer 1 had complex spatio-temporal patterns. Groups of non-CR cells showed synchronous activations and formed networks of correlated neurons superimposed in the same territory. Correlated activity among non-CR cells was mediated by a depolarizing effect of GABA and was modulated by glutamate, probably released by CR cells. Our findings demonstrate that developing layer 1 can sustain complex patterns of correlated activity and reveal a circuit mechanism that can mediate this patterned activity.}, Author = {Schwartz, T. H. and Rabinowitz, D. and Unni, V. and Kumar, V. S. and Smetters, D. K. and Tsiola, A. and Yuste, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {gamma-Aminobutyric Acid;Research Support, Non-U.S. Gov't;Electric Stimulation;Animals;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Rats;Glutamic Acid;Norepinephrine;Synaptic Transmission;Excitatory Amino Acid Agonists;Neurotransmitter Agents;Rats, Sprague-Dawley;Patch-Clamp Techniques;Tetrodotoxin;Calcium;Time Factors;21 Calcium imaging;Organ Culture Techniques;Acetylcholine;N-Methylaspartate;21 Neurophysiology;21 Circuit structure-function;Neurons;Adrenergic alpha-Agonists;Cerebral Cortex;Muscimol;24 Pubmed search results 2008;GABA Agonists}, Medline = {98198529}, Month = {3}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Biological Sciences, Columbia University, New York, New York 10027, USA.}, Pages = {541-52}, Pii = {S0896-6273(00)80993-9}, Pubmed = {9539127}, Title = {Networks of coactive neurons in developing layer 1}, Uuid = {6708C65B-6D0A-44C0-AFA3-F187187923B4}, Volume = {20}, Year = {1998}} @article{Schwartz:2006, Abstract = {Microglia, the standby cells for immune defense in the CNS, have a reputation for exacerbating the neural damage that occurs in neurodegenerative diseases. However, research over the past few years has established that microglia do not constitute a single, uniform cell population, but rather comprise a family of cells with diverse phenotypes - some that are beneficial and others that the CNS can barely tolerate and that are therefore destructive. This finding raised several questions. What instructs microglia to acquire a particular phenotype, and how do these phenotypes differ? How committed are microglia to a specific phenotype? Can destructive microglia become protective, and can protective microglia retain their beneficial phenotype even when they encounter a destructive environment? Here, we address these questions, and the background of research that elicited them.}, Author = {Schwartz, and Butovsky, and Br{\"u}ck, and Hanisch,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {7808616}, Organization = {The Weizmann Institute of Science, POB 26, Rehovot, 76100, Israel.}, Pii = {S0166-2236(05)00323-1}, Pubmed = {16406093}, Title = {Microglial phenotype: is the commitment reversible?}, Uuid = {0A94FD2F-1436-4B30-858C-A09C34FE35AD}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2005.12.005}} @article{Schwartzkroin:2004, Abstract = {Cortical dysplasia syndromes--those conditions of abnormal brain structure/organization that arise during aberrant brain development--frequently involve epileptic seizures. Neuropathological and neuroradiological analyses have provided descriptions and categorizations based on gross anatomical and cellular histological features (e.g., lissencephaly, heterotopia, giant cells), as well as on the developmental mechanisms likely to be involved in the abnormality (e.g., cell proliferation, migration). Recently, the genes responsible for several cortical dysplastic conditions have been identified and the underlying molecular processes investigated. However, it is still unclear how the various structural abnormalities associated with cortical dysplasia are related to (i.e., "cause") chronic seizures. To elucidate these relationships, a number of animal models of cortical dysplasia have been developed in rats and mice. Some models are based on laboratory manipulations that injure the brain (e.g., freeze, undercut, irradiation, teratogen exposure) of immature animals; others are based on spontaneous genetic mutations or on gene manipulations (knockouts/transgenics) that give rise to abnormal cortical structures. Such models of cortical dysplasia provide a means by which investigators can not only study the developmental mechanisms that give rise to these brain lesions, but also examine the cause-effect relationships between structural abnormalities and epileptogenesis.}, Author = {Schwartzkroin, Philip A. and Roper, Steven N. and Wenzel, H. Jurgen}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0065-2598}, Journal = {Adv Exp Med Biol}, Keywords = {Epilepsy;24 Pubmed search results 2008;21 Epilepsy;21 Neurophysiology;Rats;Animals;Disease Models, Animal;Cerebral Cortex;review;Mice}, Medline = {23422622}, Nlm_Id = {0121103}, Organization = {Department of Neurological Surgery, University of California at Davis, USA.}, Pages = {145-74}, Pubmed = {15250593}, Title = {Cortical dysplasia and epilepsy: animal models}, Uuid = {BBC3FA35-E13B-451C-9E34-ED6CDE4C167F}, Volume = {548}, Year = {2004}} @article{Schwartzkroin:2000, Abstract = {Brain malformations, resulting from aberrant patterns of brain development, are highly correlated with childhood seizure syndromes, as well as with cognitive disabilities and other neurological disorders. The structural malformations, often referred to as cortical dysplasia, are extremely varied, reflecting diverse underlying processes and critical timing of the developmental aberration. Recent studies have revealed a genetic basis for many forms of dysplasia. Gene mutations responsible for such common forms of dysplasia as lissencephaly and tuberous sclerosis have been identified, and investigators are beginning to understand how these gene mutations interrupt and/or misdirect the normal developmental pattern. Laboratory investigations, using animal models of cortical dysplasia, are beginning to elucidate how these structural malformations give rise to epilepsy and other functional pathologies.}, Author = {Schwartzkroin, P. A. and Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1080-4013}, Journal = {Ment Retard Dev Disabil Res Rev}, Keywords = {Pregnancy;Cell Differentiation;Animals;Humans;Neural Pathways;Age of Onset;21 Epilepsy;review;Female;Epilepsy;Mutation;Cell Movement;Disease Models, Animal;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;Neurons;Mice, Knockout;Mice;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Cell Division;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {20561135}, Nlm_Id = {9517974}, Number = {4}, Organization = {Department of Neurological Surgery, University of Washington, Health Sciences Center, Seattle, Washington, USA.}, Pages = {268-80}, Pii = {10.1002/1098-2779(2000)6:4<268::AID-MRDD6>3.0.CO;2-B}, Pubmed = {11107192}, Title = {Cortical malformations and epilepsy}, Uuid = {A6B40EFE-0132-11DB-9E68-000D9346EC2A}, Volume = {6}, Year = {2000}, url = {papers/Schwartzkroin_MentRetardDevDisabilResRev2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/1098-2779(2000)6:4%3C268::AID-MRDD6%3E3.0.CO;2-B}} @article{Schwartzkroin:1998, Author = {Schwartzkroin, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1078-8956}, Journal = {Nat Med}, Keywords = {Epilepsy;Synapses;21 Neurophysiology;Neuronal Plasticity;Neural Inhibition;Receptors, GABA;Chronic Disease;comment;gamma-Aminobutyric Acid;Humans;24 Pubmed search results 2008;news}, Month = {10}, Nlm_Id = {9502015}, Number = {10}, Pages = {1115-6}, Pubmed = {9771735}, Title = {GABA synapses enter the molecular big time}, Uuid = {1790FD54-8500-40AD-905D-5E857F68376D}, Volume = {4}, Year = {1998}, url = {papers/Schwartzkroin_NatMed1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/2608}} @article{Schwarz:2000, Abstract = {PURPOSE: Neuronal migration disorders (NMD) are often associated with therapy-resistant epilepsy. In human cerebral cortex, this hyperexcitability has been correlated with a loss of inhibitory interneurons. We used a rat model of focal cortical NMD (microgyria) to determine whether the expression of epileptiform activity in this model coincides with a decrease in inhibitory interneurons. METHODS: In 2-to 4-month-old rats, the density of interneurons immunoreactive for gamma-aminobutyric acid (GABA), calbindin, and parvalbumin was determined in fronto-parietal cortex in nine 200-microm-wide sectors located up to 2.5 mm lateral and 2.0 mm medial from the lesion center in primary parietal cortex (Par1). Quantitative measurements in homotopic areas of age-matched sham-operated rats served as controls. RESULTS: The freeze lesion performed in newborn rat cortex resulted in adult rats with a microgyrus extending in a rostro-caudal direction from frontal to occipital cortex. The density of GABA-and parvalbumin-positive neurons in fronto-parietal cortex was not significantly different between lesioned and control animals. Only the density of calbindin-immunoreactive neurons located 1.0 mm lateral and 0.5 mm medial from the lesion was significantly (Student t test, p < 0.05) larger in freeze-lesioned rats (5,817 +/- 562 and 6,400 +/- 795 cells per mm3, respectively; n = 12) compared with measurements in homotopic regions in Par1 cortex of controls (4,507 +/- 281 and 4, 061 +/- 319 cells per mm3, respectively; n = 5). CONCLUSIONS: The previously reported widespread functional changes in this model of cortical NMD are not related to a general loss of inhibitory interneurons. Other factors, such as a decrease in GABA receptor density, modifications in GABAA receptor subunit composition, or alterations in the excitatory network, e.g., an increase in the density of calbindin-immunoreactive pyramidal cells, more likely contribute to the global disinhibition and widespread expression of pathophysiological activity in this model of cortical NMD.}, Author = {Schwarz, P. and Stichel, C. C. and Luhmann, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {gamma-Aminobutyric Acid;Animals;Humans;Frontal Lobe;Rats;Parietal Lobe;Neocortex;21 Epilepsy;Epilepsy;Cell Count;Pyramidal Cells;Rats, Wistar;Calcium-Binding Protein, Vitamin D-Dependent;Disease Models, Animal;Animals, Newborn;Freezing;21 Neurophysiology;Parvalbumins;Receptors, GABA;Adult;Neural Tube Defects;Interneurons;24 Pubmed search results 2008;Immunohistochemistry;Neural Inhibition;Research Support, Non-U.S. Gov't}, Medline = {20357668}, Month = {7}, Nlm_Id = {2983306R}, Number = {7}, Organization = {Institute of Neurophysiology, University of D{\"u}sseldorf, D{\"u}sseldorf, Germany.}, Pages = {781-7}, Pubmed = {10897147}, Title = {Characterization of neuronal migration disorders in neocortical structures: loss or preservation of inhibitory interneurons?}, Uuid = {87F1BD6E-66F0-4A45-B058-E690C0DA2BFF}, Volume = {41}, Year = {2000}} @article{Schwarz:2006, Abstract = {Small interfering RNAs (siRNAs), the guides that direct RNA interference (RNAi), provide a powerful tool to reduce the expression of a single gene in human cells. Ideally, dominant, gain-of-function human diseases could be treated using siRNAs that specifically silence the mutant disease allele, while leaving expression of the wild-type allele unperturbed. Previous reports suggest that siRNAs can be designed with single nucleotide specificity, but no rational basis for the design of siRNAs with single nucleotide discrimination has been proposed. We systematically identified siRNAs that discriminate between the wild-type and mutant alleles of two disease genes: the human Cu, Zn superoxide dismutase (SOD1) gene, which contributes to the progression of hereditary amyotrophic lateral sclerosis through the gain of a toxic property, and the huntingtin (HTT) gene, which causes Huntington disease when its CAG-repeat region expands beyond approximately 35 repeats. Using cell-free RNAi reactions in Drosophila embryo lysate and reporter assays and microarray analysis of off-target effects in cultured human cells, we identified positions within an siRNA that are most sensitive to mismatches. We also show that purine:purine mismatches imbue an siRNA with greater discriminatory power than other types of base mismatches. siRNAs in which either a G:U wobble or a mismatch is located in the "seed" sequence, the specialized siRNA guide region responsible for target binding, displayed lower levels of selectivity than those in which the mismatch was located 3' to the seed; this region of an siRNA is critical for target cleavage but not siRNA binding. Our data suggest that siRNAs can be designed to discriminate between the wild-type and mutant alleles of many genes that differ by just a single nucleotide.}, Author = {Schwarz, and Ding, and Kennington, and Moore, and Schelter, and Burchard, and Linsley, and Aronin, and Xu, and Zamore,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1553-7404}, Journal = {PLoS Genet}, Keywords = {23 RNAi;23 Technique}, Month = {9}, Nlm_Id = {101239074}, Number = {9}, Pii = {06-PLGE-RA-0180R2}, Pubmed = {16965178}, Title = {Designing siRNA That Distinguish between Genes That Differ by a Single Nucleotide}, Uuid = {FEC9B7C4-48A4-11DB-A317-000D9346EC2A}, Volume = {2}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pgen.0020140}} @article{Schwob:1994, Abstract = {Replication-incompetent retroviral vectors that encode the heritable marker enzyme, beta-galactosidase, were used to study the lineage relationships of cells in the olfactory epithelium of unmanipulated animals and in the olfactory epithelium as it reconstitutes after lesion. Virally-marked cells are categorized as to type based on their position in the epithelium and on expression of NCAM (limited to neurons) and the carbohydrate moiety recognized by Griffonia lectin (limited to the dark/horizontal basal cells and the microvillar class of supporting cells). Direct injections of the vectors into the olfactory epithelium of otherwise intact animals produce clusters of beta-galactosidase-labeled cells when assessed 6-10 days after infection; these clusters are composed of neurons and NCAM-negative/lectin-negative light/globose basal cells exclusively. In contrast, clusters of virally-marked cells after MeBr-induced lesion of the epithelium frequently contain both neurons and supporting cells, as well as both types of basal cells. Other clusters contain supporting cells and/or Bowman's gland/duct cells. It is likely that the clusters of marked cells are derived from a single founder cell, i.e. the cells are clonal and lineally related, since the clusters are widely dispersed. Furthermore, infusion of mixtures of viruses that can be distinguished on the basis of the type and subcellular localization of the marker enzyme that is expressed produce clusters that are homogenous with respect to enzyme type, providing strong evidence in favor of the notion that the clusters are clonal in nature. Thus, the founders of the clones that contain neurons, supporting cells and basal cells are pluripotent in their capacity for differentiation. It is unlikely that the pluripotent cells are found in Bowman's gland/duct, since we have yet to observe a clone that contains neurons and cells in Bowman's gland/duct. Hence, the pluripotent stem cells are to be found in the basal cell compartment of the epithelium. However, the exact nature of these stem cells remains unknown and a subject for future investigation. eng Journal Article}, Author = {Schwob, J. E. and Huard, J. M. and Luskin, M. B. and Youngentob, S. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0379-864X}, Journal = {Chem Senses}, Keywords = {Cell Adhesion Molecules, Neuronal/biosynthesis;Genetic Vectors;Mitosis/physiology;Cell Line;Immunohistochemistry;Male;Retroviridae/*genetics;Mitosis;beta-Galactosidase/genetics;Genetic Vectors/*physiology;Animals;I abstr;Plant Lectins;Research Support, U.S. Gov't, P.H.S.;Hydrocarbons, Brominated;Olfactory Mucosa/cytology/metabolism/*physiology;Olfactory Mucosa;Support, U.S. Gov't, P.H.S.;Lectins;Animal;Neurons/enzymology/metabolism/physiology;Rats, Sprague-Dawley;Hydrocarbons, Brominated/toxicity;13 Olfactory bulb anatomy;Retroviridae;beta-Galactosidase;02 Adult neurogenesis migration;Rats;Cell Adhesion Molecules, Neuronal;Neurons}, Medline = {95253830}, Month = {12}, Nlm_Id = {8217190}, Number = {6}, Organization = {Department of Anatomy and Cell Biology, SUNY Health Science Center, Syracuse 13210, USA.}, Pages = {671-82.}, Pubmed = {7735846}, Title = {Retroviral lineage studies of the rat olfactory epithelium}, Uuid = {C82592C1-79B5-4427-B0EE-702B75FD7376}, Volume = {19}, Year = {1994}} @article{Schwob:2001, Abstract = {Viral upper respiratory infections are the most common cause of clinical olfactory dysfunction, but the pathogenesis of dysosmia after viral infection is poorly understood. Biopsies of the olfactory mucosa in patients that complain of dysosmia after viral infection fall into two categories: one in which no olfactory epithelium is seen and another in which the epithelium is disordered and populated mainly by immature neurons. We have used intranasal inoculation with an olfactory bulb line variant of MHV to study the consequences of viral infection on peripheral olfactory structures. MHV OBLV has little direct effect on the olfactory epithelium, but causes extensive spongiotic degeneration and destruction of mitral cells and interneurons in the olfactory bulb such that the axonal projection from the bulb via the lateral olfactory tract is markedly reduced. Moreover, surviving mitral cells apparently remain disconnected from the sensory neuron input to the glomerular layer, judging from retrograde labeling studies using Dil. The damage to the bulb indirectly causes a persistent, long-term increase in the turnover of sensory neurons in the epithelium, i.e. the relative proportion of immature to mature sensory neurons and the rate of basal cell proliferation both increase. The changes that develop after inoculation with MHV OBLV closely resemble the disordering of the olfactory epithelium in some patient biopsies. Thus, damage to the olfactory nerve or bulb may contribute to a form of post-viral olfactory dysfunction and MHV OBLV is a useful model for studying the pathogenesis of this form of dysosmia.}, Author = {Schwob, J. E. and Saha, S. and Youngentob, S. L. and Jubelt, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Chem Senses}, Keywords = {I pdf;13 Olfactory bulb anatomy}, Number = {8}, Organization = {Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA 02111, USA. jim.schwob\@tufts.edu}, Pages = {937-52.}, Title = {Intranasal inoculation with the olfactory bulb line variant of mouse hepatitis virus causes extensive destruction of the olfactory bulb and accelerated turnover of neurons in the olfactory epithelium of mice}, Uuid = {364E6366-D4EA-4ECE-B27B-8C89546CB5E4}, Volume = {26}, Year = {2001}, url = {papers/Schwob_ChemSenses2001}} @article{Sciamanna:2005, Abstract = {Undifferentiated cells and embryos express high levels of endogenous non-telomerase reverse transcriptase (RT) of retroposon/retroviral origin. We previously found that RT inhibitors modulate cell growth and differentiation in several cell lines. We have now sought to establish whether high levels of RT activity are directly linked to cell transformation. To address this possibility, we have employed two different approaches to inhibit RT activity in melanoma and prostate carcinoma cell lines: pharmacological inhibition by two characterized RT inhibitors, nevirapine and efavirenz, and downregulation of expression of RT-encoding LINE-1 elements by RNA interference (RNAi). Both treatments reduced proliferation, induced morphological differentiation and reprogrammed gene expression. These features are reversible upon discontinuation of the anti-RT treatment, suggesting that RT contributes to an epigenetic level of control. Most importantly, inhibition of RT activity in vivo antagonized tumor growth in animal experiments. Moreover, pretreatment with RT inhibitors attenuated the tumorigenic phenotype of prostate carcinoma cells inoculated in nude mice. Based on these data, the endogenous RT can be regarded as an epigenetic regulator of cell differentiation and proliferation and may represent a novel target in cancer therapy.}, Author = {Sciamanna, Ilaria and Landriscina, Matteo and Pittoggi, Carmine and Quirino, Michela and Mearelli, Cristina and Beraldi, Rosanna and Mattei, Elisabetta and Serafino, Annalucia and Cassano, Alessandra and Sinibaldi-Vallebona, Paola and Garaci, Enrico and Barone, Carlo and Spadafora, Corrado}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0950-9232}, Journal = {Oncogene}, Keywords = {Microscopy, Confocal;Research Support, Non-U.S. Gov't;Enzyme Inhibitors;RNA-Directed DNA Polymerase;Reverse Transcriptase Polymerase Chain Reaction;Cell Line, Tumor;Melanoma;Cell Division;Cell Cycle;22 Stem cells;15 Retrovirus mechanism;22 Cancer;Humans;RNA, Small Interfering;24 Pubmed search results 2008;Bromodeoxyuridine}, Month = {6}, Nlm_Id = {8711562}, Number = {24}, Organization = {Istituto Superiore di Sanit\`{a}, Viale Regina Elena 299, Via del Castro Laurenziano 25, 00161 Rome, Italy.}, Pages = {3923-31}, Pii = {1208562}, Pubmed = {15806170}, Title = {Inhibition of endogenous reverse transcriptase antagonizes human tumor growth}, Uuid = {2463D447-EE54-11DA-8605-000D9346EC2A}, Volume = {24}, Year = {2005}, url = {papers/Sciamanna_Oncogene2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.onc.1208562}} @article{Seaberg:2002, Abstract = {Neurogenesis persists in two adult brain regions: the ventricular subependyma and the subgranular cell layer in the hippocampal dentate gyrus (DG). Previous work in many laboratories has shown explicitly that multipotential, self-renewing stem cells in the subependyma are the source of newly generated migrating neurons that traverse the rostral migratory stream and incorporate into the olfactory bulb as interneurons. These stem cells have been specifically isolated from the subependyma, and their properties of self-renewal and multipotentiality have been demonstrated in vitro. In contrast, it is a widely held assumption that the "hippocampal"stem cells that can be isolated in vitro from adult hippocampus reside in the neurogenic subgranular layer and represent the source of new granule cell neurons, but this has never been tested directly. Primary cell isolates derived from the precise microdissection of adult rodent neurogenic regions were compared using two very different commonly used culture methods: a clonal colony-forming (neurosphere) assay and a monolayer culture system. Importantly, both of these culture methods generated the same conclusion: stem cells can be isolated from hippocampus-adjacent regions of subependyma, but the adult DG proper does not contain a population of resident neural stem cells. Indeed, although the lateral ventricle and other ventricular subependymal regions directly adjacent to the hippocampus contain neural stem cells that exhibit long-term self-renewal and multipotentiality, separate neuronal and glial progenitors with limited self-renewal capacity are present in the adult DG, suggesting that neuron-specific progenitors and not multipotential stem cells are the source of newly generated DG neurons throughout adulthood. 21871798 1529-2401 Journal Article}, Author = {Seaberg, R. M. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {J Neurosci}, Keywords = {B-24;Cerebral Ventricles/*cytology;Colony-Forming Units Assay;Cells, Cultured;Neurons/*cytology;Aging;Rats;Proteoglycans;Animal;Cell Count;Drug Combinations;Ependyma/*cytology;Laminin;Stem Cells/*cytology;Dentate Gyrus/*cytology;Male;Rats, Wistar;Animals, Newborn;Support, Non-U.S. Gov't;Spheroids/cytology;Mice;Cell Differentiation/physiology;Immunohistochemistry;Artifacts;Collagen;Neuroglia/cytology;Clone Cells/cytology}, Number = {5}, Organization = {Department of Anatomy and Cell Biology, University of Toronto, Toronto M5S 1A8, Canada. raewyn.seaberg\@utoronto.ca}, Pages = {1784-93}, Pubmed = {11880507}, Title = {Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors}, Uuid = {AD8AFEE2-A3E5-11DA-AB00-000D9346EC2A}, Volume = {22}, Year = {2002}, url = {papers/Seaberg_JNeurosci2002.pdf}} @article{Seamon:2002, Abstract = {The effects of inserting reported nuclear localization signals (NLSs) into the Moloney murine leukemia virus (Mo-MuLV) integrase (IN) protein, within a replication-competent viral construct, were studied. In contrast to the virus harboring IN fused to the simian virus 40 (SV40) large T antigen NLS (SV40 NLS) (J. A. Seamon, M. Adams, S. Sengupta, and M. J. Roth, Virology 274:412-419, 2000), a codon-modified SV40 NLS was stably expressed during viral propagation. Incorporation of the codon-modified SV40 NLS into IN, however, altered the packaging of the Gag-Pol precursor in the virus; viral particles contained decreased levels of reverse transcriptase (RT) and IN. In addition, the virus showed delayed kinetics of viral DNA synthesis upon infection. A panel of infectious MuLVs containing alternative IN-NLS fusions was generated and assayed for cell cycle-independent infection. Viral infection with the NLS-tagged proteins, however, remained dependent on passage of the cells through mitosis. This finding has direct implications for engineering murine-based retroviral vectors for gene therapy.}, Author = {Seamon, Jennifer A. and Jones, Kathryn S. and Miller, Christina and Roth, Monica J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Animals;Base Sequence;Antigens, Polyomavirus Transforming;Transfection;Cell Cycle;Integrases;15 Retrovirus mechanism;DNA Replication;Genetic Vectors;Nuclear Localization Signal;Cell Line;Moloney murine leukemia virus;Gene Therapy;Support, U.S. Gov't, P.H.S.;DNA, Viral;Virus Integration;Amino Acid Sequence;Mice;Dogs;Virus Replication;Molecular Sequence Data}, Medline = {22129266}, Month = {8}, Nlm_Id = {0113724}, Number = {16}, Organization = {Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA.}, Pages = {8475-84}, Pubmed = {12134052}, Title = {Inserting a nuclear targeting signal into a replication-competent Moloney murine leukemia virus affects viral export and is not sufficient for cell cycle-independent infection}, Uuid = {A1B3B732-6459-409E-BB37-94D722225305}, Volume = {76}, Year = {2002}, url = {papers/Seamon_JVirol2002.pdf}} @article{Sears:2003, Abstract = {Cell death plays an essential role in development, and the removal of cell corpses presents an important challenge for the developing organism. Macrophages are largely responsible for the clearance of cell corpses in Drosophila melanogaster and mammalian systems. We have examined the developmental requirement for macrophages in Drosophila and find that macrophage function is essential for central nervous system (CNS) morphogenesis. We generate and analyze mutations in the Pvr locus, which encodes a receptor tyrosine kinase of the PDGF/VEGF family that is required for hemocyte migration. We find that loss of Pvr function causes the mispositioning of glia within the CNS and the disruption of the CNS axon scaffold. We further find that inhibition of hemocyte development or of Croquemort, a receptor required for macrophage-mediated corpse engulfment, causes similar CNS defects. These data indicate that macrophage-mediated clearance of cell corpses is required for proper morphogenesis of the Drosophila CNS.}, Author = {Sears, Heather C. and Kennedy, Caleb J. and Garrity, Paul A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Research Support, Non-U.S. Gov't;Central Nervous System;Neuroglia;Research Support, U.S. Gov't, P.H.S.;Drosophila;Macrophages;Animals;24 Pubmed search results 2008;Axons}, Medline = {22694524}, Month = {8}, Nlm_Id = {8701744}, Number = {15}, Organization = {Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue 68-230B, Cambridge, MA 02139, USA.}, Pages = {3557-65}, Pubmed = {12810602}, Title = {Macrophage-mediated corpse engulfment is required for normal Drosophila CNS morphogenesis}, Uuid = {81EEEB1B-C24C-49F0-9A4D-790A3F89950A}, Volume = {130}, Year = {2003}} @article{Seeburg:2008, Abstract = {Homeostatic plasticity keeps neuronal spiking output within an optimal range in the face of chronically altered levels of network activity. Little is known about the underlying molecular mechanisms, particularly in response to elevated activity. We report that, in hippocampal neurons experiencing heightened activity, the activity-inducible protein kinase Polo-like kinase 2 (Plk2, also known as SNK) was required for synaptic scaling-a principal mechanism underlying homeostatic plasticity. Synaptic scaling also required CDK5, which acted as a "priming" kinase for the phospho-dependent binding of Plk2 to its substrate SPAR, a postsynaptic RapGAP and scaffolding molecule that is degraded following phosphorylation by Plk2. RNAi knockdown of SPAR weakened synapses, and overexpression of a SPAR mutant resistant to Plk2-dependent degradation prevented synaptic scaling. Thus, priming phosphorylation of the Plk2 binding site in SPAR by CDK5, followed by Plk2 recruitment and SPAR phosphorylation-degradation, constitutes a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity.}, Author = {Seeburg, Daniel P. and Feliu-Mojer, Monica and Gaiottino, Johanna and Pak, Daniel T. S. and Sheng, Morgan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {Animals;Immunoprecipitation;Synapses;Cells, Cultured;Serine;Rats;Neuronal Plasticity;Humans;Embryo, Mammalian;Patch-Clamp Techniques;Protein Kinases;Phosphorylation;Rats, Sprague-Dawley;Hippocampus;RNA Interference;Green Fluorescent Proteins;research support, non-u.s. gov't;Transfection;Neurons;Membrane Potentials;Cyclin-Dependent Kinase 5;24 Pubmed search results 2008;Nerve Tissue Proteins;Excitatory Postsynaptic Potentials}, Mid = {HHMIMS53372}, Month = {5}, Nlm_Id = {8809320}, Number = {4}, Organization = {The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, Pages = {571-83}, Pii = {S0896-6273(08)00267-5}, Pmc = {PMC2488274}, Pubmed = {18498738}, Title = {Critical role of CDK5 and Polo-like kinase 2 in homeostatic synaptic plasticity during elevated activity}, Uuid = {CCFA97D8-8D1F-4DF7-A923-ABDE1CAABE0F}, Volume = {58}, Year = {2008}, url = {papers/Seeburg_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.03.021}} @article{Segraves:1985, Abstract = {Using the retrograde fluorescent tracers Fast Blue and Diamidino Yellow we have studied the callosal and ipsilateral corticocortical connections between the cat's area 17/18 border region and the posteromedial lateral suprasylvian visual area (PMLS), as well as the callosal connections of each of these regions with its contralateral homologue. The main goal was to determine whether single cortical neurons project with branching axons to more than one cortical target. In addition, the double-labeling technique enabled us to examine, within a single section of cortical tissue, the relative distributions of neurons with different cortical targets. Most corticocortical neurons labeled in the area 17/18 border region and in area PMLS projected to only one of the cortical injection sites tested. When two callosal neuron types were labeled in the same area, no double-labeled neurons were found. When ipsilateral corticocortical and callosal neurons were labeled in combination, a few double-labeled neurons were found in both cortical regions examined. The most common type of double-labeled neuron was located in area PMLS and projected bilaterally to the area 17/18 border region. Our findings regarding the laminar distributions of ipsi- and contralaterally projecting neurons are in agreement with previous studies. In addition, we have found that, for callosal neurons within the upper layers of areas 17 and 18, neurons projecting to the contralateral area 17/18 border are located in the lower half of layer II/III and in upper layer IV, whereas neurons projecting to contralateral area PMLS are restricted to the lower portion of layer II/III. In addition, for callosal neurons within the deep layers of area PMLS, neurons projecting to contralateral area PMLS are located throughout layers V and VI, whereas neurons projecting to the contralateral area 17/18 border are restricted to layer VI. There are numerous other possible targets for axon collaterals not examined in this paper. However, the scarcity of neurons with multiple projections demonstrated in this study reflects the high degree of specificity of cortical connectivity. This anatomical organization may be the basis for a precise channeling of differential information at the single neuron level.}, Author = {Segraves, M. A. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Visual Cortex;Neurons;Cats;Comparative Study;Not relevant;Fluorescent Dyes;11 Glia;Support, Non-U.S. Gov't;Animals;Amidines;Corpus Callosum}, Medline = {85263807}, Month = {8}, Nlm_Id = {8102140}, Number = {8}, Pages = {2107-18}, Pubmed = {3839523}, Title = {Comparison of the distributions of ipsilaterally and contralaterally projecting corticocortical neurons in cat visual cortex using two fluorescent tracers}, Uuid = {55D5057D-41E1-48FF-B836-7FE6A7C8B4CB}, Volume = {5}, Year = {1985}} @article{Seidenfaden:2006, Abstract = {In the adult mouse forebrain, large numbers of neuronal precursors, destined to become GABA- and dopamine-producing interneurons of the olfactory bulb (OB), are generated in the subventricular zone (SVZ). Although this neurogenic system represents a potential reservoir of stem and progenitor cells for brain repair approaches, information about the survival and differentiation of SVZ-derived cells in ectopic brain regions is still fragmentary. We show here that ectopic grafting of SVZ tissue gave rise to two morphologically distinguishable cell types displaying oligodendrocytic or astrocytic characteristics. Since SVZ tissue contains neuronal and glial progenitors, we used magnetic cell sorting to deplete A2B5+ glial progenitors from the dissociated SVZ and to positively select cells that express PSA-NCAM. This procedure allowed the purification of neuronal precursors expressing TUJ1, DCX and GAD65/67. Transplantation of these cells led again to the generation of the same two glial cell types, showing that committed interneuron precursors undergo glial differentiation outside their normal environment.}, Author = {Seidenfaden, Ralph and Desoeuvre, Ang{\'e}lique and Bosio, Andreas and Virard, Isabelle and Cremer, Harold}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {24 Pubmed search results 2008}, Nlm_Id = {9100095}, Number = {1-2}, Organization = {Institut de Biologie du D{\'e}veloppement de Marseille, CNRS, Universit{\'e} de la M{\'e}diteran{\'e}e, Campus de Luminy-case 907, 13288 Marseille cedex 9, France. seidenfa\@ibdm.univ-mrs.fr}, Pages = {187-98}, Pii = {S1044-7431(06)00075-3}, Pubmed = {16730456}, Title = {Glial conversion of SVZ-derived committed neuronal precursors after ectopic grafting into the adult brain}, Uuid = {43F3DEBD-4423-11DB-A5D2-000D9346EC2A}, Volume = {32}, Year = {2006}, url = {papers/Seidenfaden_MolCellNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2006.04.003}} @article{Seipp:1997, Abstract = {Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis. Development of anti-viral strategies has been hampered by the lack of efficient cell systems to propagate HCV in vitro. To establish a long-term culture system, we tested human hepatoma (HuH7, HepG2) and porcine non-hepatoma (PK15, STE) cell lines, as well as several culture and infection conditions. As a marker for virus replication, minus-strand HCV RNA in infected cells was detected by an enhanced detection system using nested RT-PCR followed by hybridization analysis. Short-term efficiency of HCV infection (10 days) was slightly increased by addition of polyethylene glycol (PEG) and/or dimethyl sulfoxide (DMSO) to culture media during inoculation of HuH7, PK15 and STE cells, but no augmentation in long-term culture was achieved, suggesting enhanced attachment of HCV to cells rather than more efficient infection. A stabilizing effect on HCV propagation was observed for 50 days in a serum-free medium with stimulation of the low-density lipoprotein (LDL) receptor expression by lovastatin. Using partially serum-free culture conditions, long-term persistence of HCV in cells and release of virions into supernatant was achieved for up to 130 days. Infectivity of released virions in supernatants after long-term culturing (day 30-80) was shown by successful infection of fresh cells. In conclusion, supplementation with PEG, DMSO and lovastatin during inoculation did not enhance virus replication substantially, but continued stimulation of LDL-receptor expression resulted in infections which persisted for over 4 months. These data support the hypothesis of an LDL-receptor mediated uptake of HCV into cells in vitro. Journal Article}, Author = {Seipp, S. and Mueller, H. M. and Pfaff, E. and Stremmel, W. and Theilmann, L. and Goeser, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Journal = {J Gen Virol}, Keywords = {Aged;Hepacivirus/genetics/ growth &development;Human;Female;08 Aberrant cell cycle;Time Factors;EE abstr;Hepatitis C/ virology;Swine;Support, Non-U.S. Gov't;Cells, Cultured;Animals;RNA, Viral/ analysis/biosynthesis;Polymerase Chain Reaction/methods}, Organization = {Department of Internal Medicine, University of Heidelberg, Germany. Stefanie\_Seipp\@krzmail.krz.uni-heidelberg.de}, Pages = {2467-76}, Title = {Establishment of persistent hepatitis C virus infection and replication in vitro}, Uuid = {65B39FF7-9289-49C2-872A-678BAE575E1D}, Volume = {78 ( Pt 10)}, Year = {1997}} @article{Sekerkova:2004, Abstract = {Bromodeoxyuridine (BrdU) is broadly used in neuroscience to study embryonic development and adult neurogenesis. The potential toxicity of this halogenated pyrimidine analogue is frequently neglected. In this study, we administered BrdU in small doses by the progressively delayed cumulative labeling method to immunocytochemically tag different cerebellar cell types with antibodies to specific markers and BrdU in the same section. The well-known structure of the cerebellum made it possible to ascertain several toxic effects of the treatment. Time-pregnant rats were given five or six injections of 5 or 6 mg of BrdU ( approximately 12-20 mg/kg) at 8-hour intervals over 2 successive days between day 11 and 21 of pregnancy (E11-E12 to E20-E21), and the adult progeny was processed by immunocytochemistry. We demonstrate that this treatment effectively labeled distinct cerebellar cell populations but produced striking defects in the proliferation, migration, and settling of the Purkinje cells; reduced the size of the cerebellar cortex and nuclei; produced defects in the patterning of foliation; and also affected litter size, body weight, and mortality of the offspring. The observed toxic effects were consistent within individual treatment groups but varied between different treatment groups. Treatment with BrdU at the peak of neurogenesis of cerebellar projection neurons (E14) produced the most severe malformations. We observed no overt effects on the timing of neurogenesis for cerebellar neurons and glia across experimental groups. In conclusion, BrdU is a useful tool to study neural development, but its cytotoxicity represents a serious pitfall particularly when multiple doses are used to label cells. 0021-9967 Journal Article}, Author = {Sekerkova, G. and Ilijic, E. and Mugnaini, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {J Comp Neurol}, Keywords = {EE, T pdf;08 Aberrant cell cycle}, Number = {3}, Organization = {Northwestern University Institute for Neuroscience, Chicago, Illinois 60611, USA.}, Pages = {221-39}, Title = {Bromodeoxyuridine administered during neurogenesis of the projection neurons causes cerebellar defects in rat}, Uuid = {3DCF5ED6-EC97-41F8-A64A-58394DE48BCA}, Volume = {470}, Year = {2004}, url = {papers/Sekerkova_JCompNeurol2004.pdf}} @article{Seki:1996, Abstract = {We observed the enhancing effect of dimethylsulfoxide (DMSO) on infection of human T cells with human immunodeficiency virus type 1 (HIV-1). Similar enhancing effects were also found in related polar chemicals such as dimethylformamide, hexamethylenebisacetamide, sodium butyrate and retinoic acid. In acute infection of the human MT-4 T cell line, DMSO at a concentration of 1\%reduced the amounts of HIV-1 required to establish similar infection by one log. Furthermore, infection of peripheral blood lymphocytes with HIV-1 was also augmented several times by DMSO. HIV-1 production from persistently infected human T cell lines, but not monocytic cell lines, was enhanced by DMSO and related polar chemicals. DMSO enhanced transcription of HIV-1 RNA in persistently infected T cell lines, and the enhancing effect of DMSO on HIV-1 production was inhibited by staurosporine, a protein kinase inhibitor. These findings suggested that DMSO enhanced HIV-1 infection of T cells mainly at the step of transcription of viral RNA. 0006-291x Journal Article}, Author = {Seki, J. and Ikeda, R. and Hoshino, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Biochem Biophys Res Commun}, Keywords = {Tretinoin/pharmacology;Virus Replication/*drug effects;T-Lymphocytes/*drug effects/virology;EE, DMSO pdf;Human;Butyric Acid;Cell Line;HIV-1/genetics/*physiology;08 Aberrant cell cycle;Butyric Acids/pharmacology;Dimethyl Sulfoxide/*pharmacology;Support, Non-U.S. Gov't;Acetamides/pharmacology;Dimethylformamide/pharmacology}, Number = {3}, Organization = {Department of Hygiene and Virology, Gunma University School of Medicine, Japan.}, Pages = {724-9}, Title = {Dimethyl sulfoxide and related polar compounds enhance infection of human T cells with HIV-1 in vitro}, Uuid = {89CBE17D-6B28-49DA-A8BF-31D5745D0786}, Volume = {227}, Year = {1996}, url = {papers/Seki_BiochemBiophysResCommun1996.pdf}} @article{Seki:1993, Abstract = {The expression of a highly polysialylated neural cell adhesion molecule (NCAM-H) appeared in motor neurons, presumptive commissural neurons and floor plate at embryonic day 12, and then spread throughout the spinal cord during late embryonic and early postnatal stages. In the adult stage, the expression almost disappeared, but remained in the superficial laminae of the dorsal horn, the lateral spinal nucleus and the area around the central canal. These results suggest that the NCAM- H expression of the spinal cord is involved in the developmental events and possibly in the processing system of somatic and/or visceral information during the adult stage.}, Author = {Seki, T. and Arai, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Staining and Labeling;02 Adult neurogenesis migration;Tissue Distribution;Cell Adhesion Molecules, Neuronal/*metabolism;Rats;Rats, Wistar;Animal;B abstr;Aging/*metabolism;Support, Non-U.S. Gov't;Spinal Cord/embryology/growth &development/*metabolism;Immunologic Techniques}, Number = {1}, Pages = {141-5.}, Title = {Highly polysialylated NCAM expression in the developing and adult rat spinal cord}, Uuid = {A099F432-58D7-4BAA-86C0-D90D68042679}, Volume = {73}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7685664}} @article{Seki:1999, Abstract = {The granule cell layer of the adult dentate gyrus possesses two characteristics of an immature nervous system. The first is that granule cells continue to be generated in the innermost region of the granule cell layer, and newly generated and developing granule cells in the adult express highly polysialylated neural cell adhesion molecule (PSA-NCAM). PSA-NCAM-expressing apical dendrites have dynamically unstable processes such as irregular shafts and many stick-like or fan-shaped fine processes. The second is that radial glia-like cells expressing glial fibrillary acidic protein (GFAP) remain in a similar region of the granular layer. The numbers of PSA-NCAM-expressing granule cells and GFAP-expressing radial glia-like cells show a parallel age-dependent decrease during aging. Moreover, by using confocal laser scanning microscopy and immunoelectron microscopy, we demonstrated that PSA-NCAM-expressing dendrites and GFAP-expressing radial processes are partly in contact with each other, and occasionally the radial glial processes envelop the PSA-NCAM-positive dendritic processes. The temporal and spatial relationship between the two immature elements suggests that the processes of the radial glia-like cells are closely associated with the dendritic growth of the newly generated granule cells in the adult dentate gyrus and that these two immature features of neurons and glia in the dentate gyrus diminish with age.}, Author = {Seki, T. and Arai, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Glial Fibrillary Acidic Protein;10 Development;10 Hippocampus;Animals;Microscopy, Immunoelectron;Neural Cell Adhesion Molecules;Gene Expression Regulation, Developmental;Aging;Rats;Microscopy, Confocal;Rats, Wistar;Male;Dendrites;Sialic Acids;Neuroglia;Dentate Gyrus;Neurons;Neural Cell Adhesion Molecule L1;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {99332494}, Month = {8}, Nlm_Id = {0406041}, Number = {3}, Organization = {Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan. tseki\@med.juntendo.ac.jp}, Pages = {503-13}, Pii = {10.1002/(SICI)1096-9861(19990802)410:3<503::AID-CNE11>3.0.CO;2-H}, Pubmed = {10404415}, Title = {Temporal and spacial relationships between PSA-NCAM-expressing, newly generated granule cells, and radial glia-like cells in the adult dentate gyrus}, Uuid = {EC36A228-5E74-4E18-9AB5-2E6D221419DB}, Volume = {410}, Year = {1999}, url = {papers/Seki_JCompNeurol1999.pdf}} @article{Seki:2007, Abstract = {Adult neurogenesis occurs in the subgranular zone and innermost part of the dentate granule cell layer. To examine how neural precursor cells proliferate, migrate, and extend their neurites, we performed BrdU- and improved retrovirus-green fluorescence protein (GFP)-labeling analyses. Soon after labeling the majority of BrdU+ cells and GFP+ cells expressed Ki67, a cell cycle marker, and formed clusters together with PSA+ neuroblasts. Most of the Ki67+ proliferating cells expressed Hu, an immature and mature neuronal marker, and the subpopulation expressed both Hu+ and GFAP+. In the clusters, Ki67+ and PSA+ cells strongly expressed beta-catenin and N-cadherin, but PSA+ cells outside the clusters did not. Therefore, it was mainly Hu+ neuronal precursor cells that proliferated within clusters in which the cluster cells are closely associated via cell adhesion molecules, such as N-cadherin/beta-cateninIn and PSA. The newly generated cells appeared to stay in the clusters for a few days and then disperse around the clusters. The findings of this in vivo analysis and in vitro time-lapse imaging of early postnatal hippocampal slices support the notion that most postmitotic neuroblasts migrate tangentially from clusters, extending tangentially oriented processes, one of which often retains close contact with the clusters, and finally extend radial processes, or prospective apical dendrites. These results suggest that the clustering cells and tangentially migrating cells have a systematic cellular arrangement and intercellular interaction. J. Comp. Neurol. 502:275-290, 2007. (c) 2007 Wiley-Liss, Inc.}, Author = {Seki, Tatsunori and Namba, Takashi and Mochizuki, Hideki and Onodera, Masafumi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {02 Adult neurogenesis migration;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0406041}, Number = {2}, Organization = {Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan.}, Pages = {275-90}, Pubmed = {17348003}, Title = {Clustering, migration, and neurite formation of neural precursor cells in the adult rat hippocampus}, Uuid = {423C77D8-798F-4758-A8B0-FBC6C2452C93}, Volume = {502}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21301}} @article{Seki:1993a, Abstract = {We have found in the adult rat that the persistent expression of a highly polysialylated neural cell adhesion molecule (NCAM-H) that is generally specific to developing tissues, remains restrictively in the cells of the deepest portion of the dentate granular layer. Since the granule cells are known to continue to be generated in this region during the adult period, we have tried to determine whether NCAM-H is expressed by newly generated granule cells. Immunoelectron microscopic observation revealed that about half of the NCAM-H-expressing cells had the features of dentate granule cells, and that the rest of these cells appeared to be immature cells. Double immunostaining for NCAM-H and glial fibrillary acidic protein (GFAP) revealed that the NCAM-H- expressing cells differed from GFAP-positive glial cells. In rats injected with 5-bromo-2'-deoxyuridine (BrdU) at post-natal day 35, double immunostaining for NCAM-H and BrdU demonstrated that the BrdU- labeled cells expressed NCAM-H at 12 d after the injection but not at 80 d. These results provide the first direct evidence that NCAM-H is expressed transiently by newly generated granule cells that may add new neuronal circuits to the adult hippocampal formation.}, Author = {Seki, T. and Arai, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci}, Keywords = {Staining and Labeling;Granulocytes/*metabolism/ultrastructure;02 Adult neurogenesis migration;Glial Fibrillary Acidic Protein/metabolism;Cell Adhesion Molecules, Neuronal/*metabolism;Rats;Rats, Wistar;Animal;Hippocampus/cytology/*metabolism/ultrastructure;B abstr;Microscopy, Immunoelectron;Support, Non-U.S. Gov't;Bromodeoxyuridine;Male;Immunologic Techniques}, Number = {6}, Organization = {Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan.}, Pages = {2351-8.}, Title = {Highly polysialylated neural cell adhesion molecule (NCAM-H) is expressed by newly generated granule cells in the dentate gyrus of the adult rat}, Uuid = {7B9EC824-1BBB-454D-B43D-63EC9ADA8085}, Volume = {13}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7684771}} @article{Seki:2002, Abstract = {Neurogenesis is known to continue in the adult hippocampus of mammals, including humans. The present experiments were undertaken to examine the nature of developing neurons generated in the dentate gyrus of young and older rodents using immature neuronal markers such as highly polysialylated neural cell adhesion molecules (PSA-NCAM), collapsin response-mediated protein-4 (CRMP-4) and NeuroD. Most PSA-expressing cells are simultaneously positive for CRMP-4 and NeuroD in young rats. More than half of the PSA-positive cells were also positive for mature neuronal markers such as NeuN and MAP2, although the intensity of the immunoreactivities was relatively weak. BrdU analysis revealed that CRMP-4 is expressed for a longer period than PSA in BrdU-labeled neurons. The number of immature neurons expressing PSA, NeuroD or CRMP-4 decreased in older rodents, but no qualitative difference was found in the expression patterns of these molecular markers between young and older rodents. These results suggest not only that immunohistochemistry, using a combination of these immature and mature neuronal markers, is helpful for clarifying the developmental state of newly generated neurons, but also that newly generated neurons in young adult and older rodents have similar properties.}, Author = {Seki, Tatsunori}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {10 Development;Cell Differentiation;Animals;10 Hippocampus;Microtubule-Associated Proteins;Gene Expression Regulation, Developmental;Aging;Rats;Basic Helix-Loop-Helix Transcription Factors;Axons;Hippocampus;Mice, Inbred C57BL;Rats, Wistar;Male;Dendrites;Nerve Regeneration;Sialic Acids;Neurons;Dentate Gyrus;Mice;Neural Cell Adhesion Molecule L1;Immunohistochemistry;Cell Division;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {22278738}, Month = {11}, Nlm_Id = {7600111}, Number = {3}, Organization = {Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan. tseki\@med.juntendo.ac.jp}, Pages = {327-34}, Pubmed = {12391592}, Title = {Expression patterns of immature neuronal markers PSA-NCAM, CRMP-4 and NeuroD in the hippocampus of young adult and aged rodents}, Uuid = {9EDC6004-EDE9-4D66-9A05-00F33E53CCE0}, Volume = {70}, Year = {2002}, url = {papers/Seki_JNeurosciRes2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10387}} @article{Seki:1993b, Abstract = {The neural cell adhesion molecule (NCAM) is a cell surface glycoprotein which is thought to mediate cell adhesion and recognition. During developmental stages, NCAM is highly polysialylated (NCAM-H) by a unique alpha-2,8-linked polysialic acid chain (PSA), and this PSA portion of NCAM-H has been found to be closely associated with various developmental processes of the nervous system. Further, recent immunohistochemical investigations have revealed that even in the adult nervous system, a persistent PSA expression has been found confined to several regions: the olfactory bulb, the piriform cortex, the hippocampal dentate gyrus, the hypothalamus, some nuclei of the medulla and the dorsal horn of the spinal cord, which are related directly or indirectly to sensory systems. Moreover, in the dentate gyrus and olfactory bulb the expression is connected with adult neurogenesis that may add new neuronal circuits to the adult neural tissue. Therefore, the possible role of NCAM-H in the central nervous system may be associated not only with neural development, but also with adult functions, such as the processing system of sensory information and neuronal plasticity.}, Author = {Seki, T. and Arai, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Neurosci Res}, Keywords = {Cell Adhesion Molecules,;Sialic Acids/biosynthesis/chemistry/metabolism/*physiology;Central Nervous System/growth &development/*metabolism/physiology;Human;Neuronal/biosynthesis/chemistry/metabolism/*physiology;Animal;04 Adult neurogenesis factors;Support, Non-U.S. Gov't;C abstr}, Number = {4}, Organization = {Department of Anatomy, Juntendo University School of Medicine, Tokyo, Japan.}, Pages = {265-90.}, Title = {Distribution and possible roles of the highly polysialylated neural cell adhesion molecule (NCAM-H) in the developing and adult central nervous system}, Uuid = {15454CAB-1BE1-478A-AC7E-DFDB20F6A244}, Volume = {17}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8264989}} @article{Selkirk:2002, Abstract = {Advances in the development of highly infectious, replication-deficient recombinant retroviruses provide an efficient means of stable transfer of gene expression. Coupled with ex vivo transduction, surrogate cell populations can be readily implanted into the brain, thus serving as vehicles for delivering selected gene products into the central nervous system (CNS). Here we report that rat astrocytes can be routinely and safely isolated from brain tissue of a living donor by use of short-term gelatin sponge implants. The mature, nontransformed astrocytes were easily expanded, maintained in long-term tissue cultures and were efficiently transduced with an amphotropic retrovirus harboring a heterologous, fused transgene. In vitro retroviral infection rendered the nontransformed cells essentially 100\%viable after exposure. The level of efficiency of infection (30-50\%effective genome integration of provirus and expression of transgene in target cell populations) and minimal cell toxicity obviated the need to harvest large numbers of target cells. Cultured transduced astrocytes were resilient and exhibited select peptide expression for up to 1 year. Subsequently, transduced astrocytes were used in a series of experiments in which cells were transplanted intracerebrally in syngeneic animals. Post-implantation, astrocytes seeded locally and either insinuated into the surrounding parenchyma in situ or exhibited a variable degree of migration, depending on the anatomic source of astrocytes and the targeted brain implantation site. Transduced astrocytes remained viable in excess of 8 months post-transplantation and exhibited sustained transgenic peptide expression of green fluorescent protein/neomycin phosphotransferase in vivo. The sequential isolation and culture of nontransformed, mature, adult astrocytes and recombinant retrovirus-mediated transduction in vitro followed by brain reimplantation represents a safe and effective means for transferring genetic expression to the CNS. This study lays the foundation for exploring the utility of using a human autologous transplantation system as a potential gene delivery approach to treat neurological disorders. Prepared and utilized in this manner, autologous astrocytes may serve as a vehicle to deliver gene therapy to the CNS.}, Author = {Selkirk, S. M. and Greenberg, S. J. and Plunkett, R. J. and Barone, T. A. and Lis, A. and Spence, P. O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Cell Culture Techniques;Transduction, Genetic;Astrocytes;Animals;Central Nervous System Diseases;Rats;Cell Separation;Brain;Kanamycin Kinase;Retroviridae;11 Glia;Green Fluorescent Proteins;Genetic Vectors;Rats, Inbred F344;Gene Therapy;Transplantation, Autologous;Luminescent Proteins;Models, Animal;Research Support, Non-U.S. Gov't}, Medline = {21935227}, Month = {4}, Nlm_Id = {9421525}, Number = {7}, Organization = {Laboratory of Neuroimmunology and Neurovirology, Department of Neurology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.}, Pages = {432-43}, Pubmed = {11938458}, Title = {Syngeneic central nervous system transplantation of genetically transduced mature, adult astrocytes}, Uuid = {3CCBDDCF-AF95-4094-98E5-5AF9926A30E0}, Volume = {9}, Year = {2002}, url = {papers/Selkirk_GeneTher2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301643}} @article{Semkova:1999, Abstract = {Neurotrophins and other neurotrophic factors have been shown to support the survival and differentiation of many neuronal populations of the central and peripheral nervous system. Therefore, administering neurotrophic factors could represent an alternative strategy for the treatment of acute and chronic brain disorders. However, the delivery of neurotrophic factors to the brain is one of the largest obstacles in the development of effective therapy for neurodegenerative disorders, because these proteins are not able to cross the blood-brain barrier. The induction of growth factor synthesis in the brain tissue by systemically administered lipophilic drugs, such as beta-adrenoceptor agonists, shown to increase endogenous nerve growth factor (NGF) synthesis in the brain, would be an elegant way to overcome these problems of application. Stimulation of beta-adrenoceptors with clenbuterol led to increased NGF synthesis in cultured central nervous system (CNS) cells and rat brain tissue. Clenbuterol-induced NGF expression was reduced to the control levels by coadministration of beta-adrenoceptor antagonist propranolol. Furthermore, clenbuterol protected rat hippocampal neurons subjected to excitotoxic damage. The neuroprotective effect of clenbuterol in vitro depended on increased NGF synthesis, since the neuroprotection was abolished by NGF antisense oligonucleotide as well as by antibodies directed against NGF itself. In vivo, clenbuterol protected rat hippocampus in a model of transient forebrain ischemia and reduced the infarct volume in a rat model of permanent middle cerebral artery occlusion (MCAo). The neuroprotective effect of clenbuterol in vivo was accompanied by enhanced NGF synthesis in brain tissue. These findings support our hypothesis that orally active NGF inducers may have a potential as therapeutic agents for the treatment of neurodegenerative disorders and stroke.}, Author = {Semkova, I. and Krieglstein, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Brain Res Brain Res Rev}, Keywords = {Cell Differentiation;Brain/*physiology;Neuroprotective Agents;Neurons/cytology/pathology/*physiology;Rats;Human;Cell Survival;Brain Diseases/*physiopathology/therapy;Animal;04 Adult neurogenesis factors;C-10;Neurodegenerative Diseases/*physiopathology/therapy;Nerve Growth Factors/genetics/*physiology/therapeutic use}, Number = {2}, Organization = {Hannover Medical School, Center of Anatomy, OE 4140, Carl-Neuberg Str. 1, D-30623, Hannover, Germany. semkova.irina\@mh-hannover.de}, Pages = {176-88.}, Title = {Neuroprotection mediated via neurotrophic factors and induction of neurotrophic factors}, Uuid = {B01A2B79-4A47-4875-8C6C-757BD9FE5872}, Volume = {30}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10525174%20http://www.elsevier.com:80/cgi-bin/cas/tree/store/bresr/cas_sub/browse/browse.cgi?year=1999&volume=30&issue=2&aid=90260}} @article{Sengupta:2003, Abstract = {PURPOSE: Age-related macular degeneration (ARMD) is the primary cause of blindness in people aged of 50 years or more. The wet form leads to severe loss of central vision. Recent evidence supports that adult hematopoietic stem cells (HSCs) contribute to preretinal neovascularization. In the current study, it was determined whether HSCs, by producing both blood and blood vessels, provide functional hemangioblast activity during choroidal neovascularization (CNV) in mice. METHODS: Gfp chimeric mice were developed by bone marrow ablation of C57BL/6J mice and reconstitution with donor tissue from gfp(+/+) transgenic mice. Gfp chimeric mice underwent laser rupture of Bruch's membrane and were killed and eyes enucleated at 1, 2, 3, and 4 weeks after laser injury. CNV was examined by confocal microscopy of retinal flatmounts. Because endothelial progenitor cells (EPCs) derive from HSCs, immunocytochemistry was used to quantify relative the EPC contribution to CNV. RESULTS: Laser injury alone was sufficient to induce stem cell recruitment and subsequent CNV. Gfp+ cells formed part of the functional vasculature in the choroid as early as 1 week after injury and were present for the duration of the study. The relative EPC contribution to CNV remained fairly constant throughout the study and constituted almost 50\%of the total vasculature. CONCLUSIONS: Adult stem cells are recruited to the choroid in a model of CNV, where they contribute to forming aberrant new vessels. This observation suggests that targeting stem cell recruitment to the eye may offer a novel therapeutic strategy for ARMD.}, Author = {Sengupta, Nilanjana and Caballero, Sergio and Mames, Robert N. and Butler, Jason M. and Scott, Edward W. and Grant, Maria B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0146-0404}, Journal = {Invest Ophthalmol Vis Sci}, Keywords = {Blood Vessels;Fluorescent Antibody Technique, Indirect;Animals;Blood Cells;Microscopy, Confocal;Indicators and Reagents;Mice, Transgenic;Choroidal Neovascularization;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Bruch Membrane;Antigens, CD31;Hematopoietic Stem Cell Transplantation;Bone Marrow;Research Support, U.S. Gov't, P.H.S.;Flow Cytometry;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Laser Coagulation;Research Support, Non-U.S. Gov't}, Medline = {22939977}, Month = {11}, Nlm_Id = {7703701}, Number = {11}, Organization = {Program in Stem Cell Biology, University of Florida, Florida, USA.}, Pages = {4908-13}, Pubmed = {14578416}, Title = {The role of adult bone marrow-derived stem cells in choroidal neovascularization}, Uuid = {194777C5-E0B5-43BA-899B-93CC2901C2D4}, Volume = {44}, Year = {2003}} @article{Sensenbrenner:1997, Abstract = {Recent studies have revealed that proteins such as growth-associated protein 43 (GAP-43) and neuron-specific enolase (NSE), believed for many years to be expressed exclusively in neurons, are also present in glial cells under some circumstances. Here we present an overview of these observations. GAP-43 is expressed both in vitro and in vivo transiently in immature rat oligodendroglial cells of the central nervous system, in Schwann cell precursors, and in non-myelin-forming Schwann cells of the peripheral nervous system. GAP-43 mRNA is also present in oligodendroglial cells and Schwann cells, indicating that GAP-43 is synthesized in these cells. GAP-43 is also expressed in type 2 astrocytes (stellate-shaped astrocytes) and in some reactive astrocytes but not in type 1 astrocytes (flat protoplasmic astrocytes). These results suggest that GAP-43 plays a more general role in neural plasticity during development of the central and peripheral nervous systems. NSE enzymatic activity and protein and mRNA have been detected in rat cultured oligodendrocytes at levels comparable to those of cultured neurons. NSE expression increases during the differentiation of oligodendrocyte precursors into oligodendrocytes. In vivo, NSE protein is expressed in differentiating oligodendrocytes and is repressed in fully mature adult cells. The upregulation of NSE in differentiating oligodendrocytes coincides with the formation of large amounts of membrane structures and of protoplasmic processes. Similarly, NSE becomes detectable in glial neoplasms and reactive glial cells at the time when these cells undergo morphological changes. The expression of the glycolytic isozyme NSE in these cells, which do not normally contain it, could reflect a response to higher energy demands. This expression may also be related to the neurotrophic and neuroprotective properties demonstrated for this enolase isoform. NSE activity and protein and mRNA have also been found in cultured rat type 1-like astrocytes but at much lower levels than in neurons and oligodendrocytes. Thus GAP-43 and NSE should be used with caution as neuron-specific markers in studies of normal and pathological neural development.}, Author = {Sensenbrenner, M. and Lucas, M. and Deloulme, J. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0946-2716}, Journal = {J Mol Med}, Keywords = {01 Adult neurogenesis general;Neuroglia;Central Nervous System;Research Support, Non-U.S. Gov't;Rats;Schwann Cells;Astrocytes;Phosphopyruvate Hydratase;GAP-43 Protein;Cells, Cultured;Animals;24 Pubmed search results 2008;review}, Medline = {98012069}, Month = {9}, Nlm_Id = {9504370}, Number = {9}, Organization = {Laboratoire de Neurobiologie Ontog{\'e}nique, CNRS ERS 110, Centre de Neurochimie, Strasbourg, France.}, Pages = {653-63}, Pubmed = {9351704}, Title = {Expression of two neuronal markers, growth-associated protein 43 and neuron-specific enolase, in rat glial cells}, Uuid = {E65819E3-2902-4148-AD25-36419D418E0B}, Volume = {75}, Year = {1997}} @article{Sereno:2005, Author = {Sereno, Martin I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Aging;Retina;Visual Cortex;Visual Perception;Macaca mulatta;Neuronal Plasticity;Models, Neurological;Reproducibility of Results;comment;Humans;Animals;24 Pubmed search results 2008;news}, Month = {5}, Nlm_Id = {0410462}, Number = {7040}, Pages = {288-9}, Pii = {435288a}, Pubmed = {15902243}, Title = {Neuroscience: plasticity and its limits}, Uuid = {6E7C5C46-120D-4642-8FD0-D104A93E119A}, Volume = {435}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/435288a}} @article{Seress:1991, Abstract = {Calcium-binding proteins calbindin D28k (CaBP) and parvalbumin (PV) were localized in neurons of the monkey hippocampal formation. CaBP immunoreactivity is present in all granule cells and in a large proportion of CA1 and CA2 pyramidal neurons, as well as in a distinct population of local circuit neurons. In the dentate gyrus, CaBP-immunoreactive nongranule cells are present in the molecular layer and in the hilar region, but they do not include the pyramidal basket cells at the hilar border. In the Ammon's horn, CaBP-positive, nonpyramidal neurons are more frequent in the CA3 area than in any other parts of the hippocampal formation. They are concentrated in the strata oriens and pyramidale of areas CA1-3, whereas only a few small neurons were found in the strata lucidum and radiatum of CA3 and in the stratum moleculare of the CA1 area. PV is exclusively present in local circuit neurons both in the dentate gyrus and in Ammon's horn. In the dentate gyrus the presumed basket cells at the hilar border exhibit PV immunoreactivity. In the hilar region and molecular layer only a relatively small number of cells are immunoreactive for PV. Most of these PV-positive cell bodies are located in the inner half of the molecular layer, with occasional horizontal cells at the hippocampal fissure. In Ammon's horn, strata oriens and pyramidale of areas CA1-3 contain a large number of PV-positive cells. There are no PV-immunoreactive cells in the strata lucidum, radiatum, or lacunosum moleculare. The CaBP- and PV-containing neurons form different subpopulations of cells in the monkey hippocampal formation. With the exception of a basket cell type in the monkey dentate gyrus, the CaBP- and PV-positive cell types were found to be remarkably similar in rodents and primates.}, Author = {Seress, L. and Guly{\'a}s, A. I. and Freund, T. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {10 Development;Research Support, Non-U.S. Gov't;Calcium-Binding Protein, Vitamin D-Dependent;Macaca mulatta;Female;10 Hippocampus;Immunohistochemistry;Parvalbumins;Hippocampus;Pyramidal Tracts;Interneurons;Animals;Neurons}, Medline = {92105482}, Month = {11}, Nlm_Id = {0406041}, Number = {1}, Organization = {Department of Physiology, University Medical School P{\'e}cs, Hungary.}, Pages = {162-77}, Pubmed = {1761752}, Title = {Parvalbumin- and calbindin D28k-immunoreactive neurons in the hippocampal formation of the macaque monkey}, Uuid = {111B4FE6-CC41-41B5-990E-FEF3C8856464}, Volume = {313}, Year = {1991}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.903130112}} @article{Seri:2004, Abstract = {New neurons continue to be born in the subgranular zone (SGZ) of the dentate gyrus in the hippocampus of adult mammals, including humans. Previous work has shown that astrocytes function as the progenitors of these new neurons through immature intermediate D cells. In the first part of the present study, we determined the structure of each of these progenitors and how they are organized in three dimensions. Serial-section reconstructions of the SGZ, using confocal and electron microscopy demonstrate that SGZ astrocytes form baskets that hold clusters of D cells, largely insulating them from the hilus. Two types of glial fibrillary acidic protein-expressing astrocytes (radial and horizontal) and three classes of doublecortin and PSA-NCAM-positive D cells (D1, D2, D3) were observed. Radial astrocytes appear to interact closely with clusters of D cells forming radial proliferative units. In the second part of this study, we show that retrovirally labeled radial astrocytes give rise to granule neurons. We also used bromodeoxyuridine and [3H]thymidine labeling to study the sequence of appearance of the different D cells after a 7-day treatment with anti-mitotics. This analysis, together with retroviral labeling data, suggest that radial astrocytes divide to generate D1 cells, which in turn divide once to form postmitotic D2 cells. D2 cells mature through a D3 stage to form new granule neurons. These observations provide a model of how the germinal zone of the adult hippocampus is organized and suggest a sequence of cellular stages in the generation of new granule neurons.}, Author = {Seri, Bettina and Garc{\'\i}a-Verdugo, Jos{\'e} Manuel and Collado-Morente, Lucia and McEwen, Bruce S. and Alvarez-Buylla, Arturo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Cell Differentiation;10 Development;03 Adult neurogenesis progenitor source;Comparative Study;10 Hippocampus;Dentate Gyrus;Germ Layers;Research Support, U.S. Gov't, P.H.S.;Animals;Mice;Cell Lineage}, Month = {10}, Nlm_Id = {0406041}, Number = {4}, Organization = {University of California, San Francisco, Department of Neurological Surgery and Program in Developmental and Stem Cell Research, San Francisco, California 94143, USA.}, Pages = {359-78}, Pubmed = {15384070}, Title = {Cell types, lineage, and architecture of the germinal zone in the adult dentate gyrus}, Uuid = {4380B721-7FED-11DA-9A2D-000D9346EC2A}, Volume = {478}, Year = {2004}, url = {papers/Seri_JCompNeurol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.20288}} @article{Seri:2001, Abstract = {Neurogenesis in the dentate gyrus of the hippocampus persists throughout life in many vertebrates, including humans. The progenitors of these new neurons reside in the subgranular layer (SGL) of the dentate gyrus. Although stem cells that can self-renew and generate new neurons and glia have been cultured from the adult mammalian hippocampus, the in vivo primary precursors for the formation of new neurons have not been identified. Here we show that SGL cells, which express glial fibrillary acidic protein and have the characteristics of astrocytes, divide and generate new neurons under normal conditions or after the chemical removal of actively dividing cells. We also describe a population of small electron-dense SGL cells, which we call type D cells and are derived from the astrocytes and probably function as a transient precursor in the formation of new neurons. These results reveal the origins of new neurons in the adult hippocampus.}, Author = {Seri, B. and Garcia-Verdugo, J. M. and McEwen, B. S. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {J Neurosci}, Keywords = {02 Adult neurogenesis migration;10 Development;03 Adult neurogenesis progenitor source;10 Hippocampus;BB}, Number = {18}, Organization = {The Rockefeller University, New York, New York 10021, USA.}, Pages = {7153-60.}, Title = {Astrocytes give rise to new neurons in the adult mammalian hippocampus}, Uuid = {F21C94AB-6875-11DA-A4B6-000D9346EC2A}, Volume = {21}, Year = {2001}, url = {papers/Seri_JNeurosci2001}} @article{Serizawa:2006, Abstract = {In the mouse, olfactory sensory neurons (OSNs) expressing the same odorant receptor (OR) converge their axons to a specific set of glomeruli in the olfactory bulb. To study how OR-instructed axonal fasciculation is controlled, we searched for genes whose expression profiles are correlated with the expressed ORs. Using the transgenic mouse in which the majority of OSNs express a particular OR, we identified such genes coding for the homophilic adhesive molecules Kirrel2/Kirrel3 and repulsive molecules ephrin-A5/EphA5. In the CNGA2 knockout mouse, where the odor-evoked cation influx is disrupted, Kirrel2 and EphA5 were downregulated, while Kirrel3 and ephrin-A5 were upregulated, indicating that these genes are transcribed in an activity-dependent manner. Mosaic analysis demonstrated that gain of function of these genes generates duplicated glomeruli. We propose that a specific set of adhesive/repulsive molecules, whose expression levels are determined by OR molecules, regulate the axonal fasciculation of OSNs during the process of glomerular map formation.}, Author = {Serizawa, Shou and Miyamichi, Kazunari and Takeuchi, Haruki and Yamagishi, Yuya and Suzuki, Misao and Sakano, Hitoshi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Models, Biological;Protein Binding;24 Pubmed search results 2008;research support, non-u.s. gov't;Carrier Proteins;Cell Adhesion Molecules;Membrane Proteins;Ephrin-A5;Receptor, EphA5;Mice, Transgenic;Olfactory Bulb;Neurons, Afferent;Animals;Mice;Receptors, Odorant;13 Olfactory bulb anatomy;Axons}, Month = {12}, Nlm_Id = {0413066}, Number = {5}, Organization = {Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo 113-0032, Japan.}, Pages = {1057-69}, Pii = {S0092-8674(06)01404-8}, Pubmed = {17129788}, Title = {A neuronal identity code for the odorant receptor-specific and activity-dependent axon sorting}, Uuid = {F298058E-76BB-4682-952F-84E34DE87F9C}, Volume = {127}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.10.031}} @article{Shah:2008, Abstract = {During development, spontaneous retinal waves are thought to provide an instructive signal for retinotopic map formation in the superior colliculus. In mice lacking the beta2 subunit of nicotinic ACh receptors (beta2-/-), correlated retinal waves are absent during the first postnatal week, but return during the second postnatal week. In control retinocollicular synapses, in vitro analysis reveals that AMPA/NMDA ratios and AMPA quantal amplitudes increase during the first postnatal week while the prevalence of silent synapses decreases. In age-matched beta2-/- mice, however, these parameters remain unchanged through the first postnatal week in the absence of retinal waves, but quickly mature to control levels by the end of the second week, suggesting that the delayed onset of correlated waves is able to drive synapse maturation. To examine whether such a mechanistic relationship exists, we applied a "burst-based" plasticity protocol that mimics coincident activity during retinal waves. We find that this pattern of activation is indeed capable of inducing synaptic strengthening [long-term potentiation (LTP)] on average across genotypes early in the first postnatal week [postnatal day 3 (P3) to P4] and, interestingly, that the capacity for LTP at the end of the first week (P6-P7) is significantly greater in immature beta2-/- synapses than in mature control synapses. Together, our results suggest that retinal waves drive retinocollicular synapse maturation through a learning rule that is physiologically relevant to natural wave statistics and that these synaptic changes may serve an instructive role during retinotopic map refinement.}, Author = {Shah, Ruchir D. and Crair, Michael C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2013-05-21 19:47:22 +0000}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;Retina;Electric Stimulation;Animals;Synapses;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Neuronal Plasticity;Superior Colliculi;Synaptic Transmission;Patch-Clamp Techniques;Visual Pathways;Behavior, Animal;Quinoxalines;Animals, Newborn;N-Methylaspartate;21 Neurophysiology;Mice, Knockout;Age Factors;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Dose-Response Relationship, Radiation;Receptors, Nicotinic;in vitro; 21 Activity-development; currOpinRvw}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Pages = {292-303}, Pii = {28/1/292}, Pubmed = {18171946}, Title = {Retinocollicular synapse maturation and plasticity are regulated by correlated retinal waves}, Uuid = {315846E2-B43B-49E5-9185-55B9E76F9841}, Volume = {28}, Year = {2008}, url = {papers/Shah_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4276-07.2008}} @article{Shah:2004, Abstract = {The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurons in chronic epilepsy. Discerning the mechanisms underlying signal integration within EC neurons is essential for understanding network excitability alterations involving the hippocampus during epilepsy. Twenty-four hours following a single seizure episode when there were no behavioral or electrographic seizures, we found enhanced spontaneous activity still present in the rat EC in vivo and in vitro. The increased excitability was accompanied by a profound reduction in I(h) in EC layer III neurons and a significant decline in HCN1 and HCN2 subunits that encode for h channels. Consequently, dendritic excitability was enhanced, resulting in increased neuronal firing despite hyperpolarized membrane potentials. The loss of I(h) and the increased neuronal excitability persisted for 1 week following seizures. Our results suggest that dendritic I(h) plays an important role in determining the excitability of EC layer III neurons and their associated neural networks.}, Author = {Shah, Mala M. and Anderson, Anne E. and Leung, Victor and Lin, Xiaodi and Johnston, Daniel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't ;24 Pubmed search results 2008;GABA Antagonists;Immunohistochemistry;Male;Kainic Acid;Animals;research support, u.s. gov't, p.h.s. ;comparative study ;Entorhinal Cortex;Analysis of Variance;Seizures;Excitatory Amino Acid Agonists;Ion Channels;Neuronal Plasticity;Dendrites;Membrane Potentials;Pyramidal Cells;Rats, Sprague-Dawley;Blotting, Western;Rats;Patch-Clamp Techniques;Pyrimidines;Bicuculline;21 Neurophysiology;Valine;Electroencephalography;Muscle Proteins;in vitro ;Excitatory Postsynaptic Potentials}, Month = {10}, Nlm_Id = {8809320}, Number = {3}, Organization = {Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.}, Pages = {495-508}, Pii = {S0896627304006749}, Pubmed = {15504329}, Title = {Seizure-induced plasticity of h channels in entorhinal cortical layer III pyramidal neurons}, Uuid = {07079249-2CB8-432E-969A-7D5DE3B723E1}, Volume = {44}, Year = {2004}, url = {papers/Shah_Neuron2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.10.011}} @article{Shalizi:2006, Abstract = {Postsynaptic differentiation of dendrites is an essential step in synapse formation. We report here a requirement for the transcription factor myocyte enhancer factor 2A (MEF2A) in the morphogenesis of postsynaptic granule neuron dendritic claws in the cerebellar cortex. A transcriptional repressor form of MEF2A that is sumoylated at lysine-403 promoted dendritic claw differentiation. Activity-dependent calcium signaling induced a calcineurin-mediated dephosphorylation of MEF2A at serine-408 and, thereby, promoted a switch from sumoylation to acetylation at lysine-403, which led to inhibition of dendritic claw differentiation. Our findings define a mechanism underlying postsynaptic differentiation that may modulate activity-dependent synapse development and plasticity in the brain.}, Author = {Shalizi, Aryaman and Gaudilli\`{e}re, Brice and Yuan, Zengqiang and Stegm{\"u}ller, Judith and Shirogane, Takahiro and Ge, Qingyuan and Tan, Yi and Schulman, Brenda and Harper, J. Wade and Bonni, Azad}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Transcription, Genetic;10 Development;Cell Differentiation;Calcium Signaling;Animals;Synapses;In Vitro;Rats;Transfection;Acetylation;Humans;Phosphorylation;Electroporation;RNA Interference;Recombinant Fusion Proteins;Calcium;Small Ubiquitin-Related Modifier Proteins;Dendrites;Cerebellar Cortex;Myogenic Regulatory Factors;Cell Line;Morphogenesis;Neurons;Calcineurin;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't}, Month = {2}, Nlm_Id = {0404511}, Number = {5763}, Organization = {Department of Pathology, Harvard Medical School, 77 Louis Pasteur Avenue, Boston, MA 02115, USA.}, Pages = {1012-7}, Pii = {311/5763/1012}, Pubmed = {16484498}, Title = {A calcium-regulated MEF2 sumoylation switch controls postsynaptic differentiation}, Uuid = {82661870-3CDA-4C9F-BF00-0FECD0C8384B}, Volume = {311}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1122513}} @article{Shaner:2004, Abstract = {Fluorescent proteins are genetically encoded, easily imaged reporters crucial in biology and biotechnology. When a protein is tagged by fusion to a fluorescent protein, interactions between fluorescent proteins can undesirably disturb targeting or function. Unfortunately, all wild-type yellow-to-red fluorescent proteins reported so far are obligately tetrameric and often toxic or disruptive. The first true monomer was mRFP1, derived from the Discosoma sp. fluorescent protein "DsRed" by directed evolution first to increase the speed of maturation, then to break each subunit interface while restoring fluorescence, which cumulatively required 33 substitutions. Although mRFP1 has already proven widely useful, several properties could bear improvement and more colors would be welcome. We report the next generation of monomers. The latest red version matures more completely, is more tolerant of N-terminal fusions and is over tenfold more photostable than mRFP1. Three monomers with distinguishable hues from yellow-orange to red-orange have higher quantum efficiencies.}, Author = {Shaner, Nathan C. and Campbell, Robert E. and Steinbach, Paul A. and Giepmans, Ben N. G. and Palmer, Amy E. and Tsien, Roger Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {letter;23 Technique}, Month = {12}, Nlm_Id = {9604648}, Number = {12}, Pages = {1567-72}, Pii = {nbt1037}, Pubmed = {15558047}, Title = {Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein}, Uuid = {E1B32A1E-9E5A-4F00-A239-D8E16748B002}, Volume = {22}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt1037}} @article{Shankle:1998, Abstract = {The generalization of the finding of no postnatal neurogenesis in non-human primates to humans may be incorrect because: (1) rhesus macaques belong to a superfamily that diverged more than 25 million years ago from the superfamily including the genus Homo; (2) the pulse thymidine labeling method, which demonstrates DNA synthesis rather than mitosis per se, is less reliable than some have assumed. This study examines changes in the number of neurons in a column underneath a cortical surface area of 1 mm2, extending through all cortical layers (mm2-column) for 35 gyri (representing about 73\%of the human cerebral cortex) based on the data of J.L. Conel (1939 to 1967). We corrected these data, derived from his measures of cortical neuronal packing density, somal breadth and height, and cortical layer thickness at postnatal ages 0, 1, 3, 6, 15, 24, 48, and 72 months, for shrinkage and stereological errors. In all 35 gyri, neuron number/mm2-column: (1) initially declines (mu = 46\%decline, sigma = 8\%), 95\%of which is due to surface area expansion (mean age of nadir value = 15.8 months); (2) then increases to age 72 months by 70\%(mu = 1.7-fold increase, (mu rate = 1.1\%per month). Because of a a concomitant 1.3-fold increase in cortical surface from 15 to 72 months, total cortical neuron number increases 2.2-fold. The close agreement between neuron number/mm2-column for Conel's age 72-month data to the corresponding values reported by others for adult human and primate cortex using more modern methods suggests the finding is not an artifact. Neuronal proliferative fate-determining factors provide at least four mechanisms for increasing cortical neuron number postnatally, with or without DNA synthesis.}, Author = {Shankle, W. R. and Landing, B. H. and Rafii, M. S. and Schiano, A. and Chen, J. M. and Hara, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0022-5193}, Journal = {J Theor Biol}, Keywords = {Cell Survival;Cell Differentiation;Animals;Child, Preschool;Humans;Aging;Databases, Factual;Macaca;Female;Phylogeny;Infant;Cell Count;Computational Biology;Macaca fascicularis;Child;Cell Movement;Male;Statistics;Cerebral Cortex;Neurons;Infant, Newborn;Cell Division;Brain Mapping}, Medline = {98295040}, Month = {3}, Nlm_Id = {0376342}, Number = {2}, Organization = {Department of Cognitive Sciences, University of California, Irvine 92697-5100, USA. rshankle\@uci.edu}, Pages = {115-40}, Pii = {S0022519397905701}, Pubmed = {9631564}, Title = {Evidence for a postnatal doubling of neuron number in the developing human cerebral cortex between 15 months and 6 years}, Uuid = {BAA15396-C26D-11DA-969D-000D9346EC2A}, Volume = {191}, Year = {1998}, url = {papers/Shankle_JTheorBiol1998.pdf}} @article{Shapiro:2007, Abstract = {The Drosophila Dscams are immunoglobulin superfamily members produced from a single gene that is diversified by alternative splicing to produce a family of cell-surface proteins with over 19,000 different ectodomain isoforms. Dscams are critical for neuronal wiring, and mounting evidence suggests that they play a key role in self-avoidance between sister branches from neurons, which depends on homophilic self-recognition by Dscams. Two recent papers shed new light on Dscam recognition: first by showing that the vast majority of Dscam isoforms mediate specific homophilic binding and second by revealing the essence of the molecular basis of homophilic recognition by Dscams through high-resolution structural studies.}, Author = {Shapiro, Lawrence}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Biochemistry and Molecular Biophysics and Edward S Harkness Eye Institute, Columbia University, New York, NY 10032, USA. lss8\@columbia.edu}, Pages = {10-3}, Pii = {S0896-6273(07)00722-2}, Pubmed = {17920010}, Title = {Self-recognition at the atomic level: understanding the astonishing molecular diversity of homophilic Dscams}, Uuid = {9999FD48-A670-4B31-B1CB-055BA7314305}, Volume = {56}, Year = {2007}, url = {papers/Shapiro_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.09.024}} @article{Shariful-Islam:1998, Abstract = {To investigate the possible role of nitric oxide (NO) in adult neurogenesis and neuron-glial migration in the rostral migratory stream (RMS), we used a double-labeled immunofluorescence technique together with confocal laser scanning microscopy, and examined the localization of nitric oxide synthase (NOS), the highly polysialylated isoform of neural cell adhesion molecule (PSA-N-CAM), and the astroglial marker in brain, S100 protein (S100), throughout the length of the subependymal layer (SEL) to olfactory bulb (OB) pathway of the adult guinea pig forebrain. Blast-like, beaded, clustered immature cellular elements stained for PSA-N-CAM and those having a typical astrocytic phenotypes positive for S100 protein were densely interlaced throughout the entire length of the SEL. Some S100 positive ependymoglial cells (tanycytes) gave off their basal projections into the closely packed PSA-N-CAM immunopositive clusters in the rostral extension of the subependymal zone (SEZre). The SEL was devoid of NOS immunoreactivity. A dense network of punctate, fenestrated and radially oriented immature cellular elements positive both for NOS and PSA-N-CAM intermingled and overlapped in the inner part of the internal granular layer (IGr), whereas in the outer part, PSA-N-CAM expression gradually diminished and the cells shifted to mature bipolar, spherical or spindle-shaped granule cells with uniform cellular contours, which were exclusively immunopositive for NOS. Radially oriented astroglial phenotypes were intertwined with PSA-N-CAM neuronal clusters in the SEL, and were closely apposed to NOS neuronal elements in the IGr. In summary, these results showed a distinct separation of neurons and glia as revealed by PSA-N-CAM and S100 protein immunostaining, and an inverse spatio- temporal correlation of expression between PSA-N-CAM (immature neuroblasts) and NOS (mature neurons) in the adult guinea pig RMS.}, Author = {Shariful Islam, A. T. and Nakamura, K. and Seki, T. and Kuraoka, A. and Hirata, K. and Emson, P. C. and Kawabuchi, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Microscopy, Confocal;Nitric-Oxide Synthase/*biosynthesis;C;Female;Immunohistochemistry;Neural Cell Adhesion Molecules/*biosynthesis;Guinea Pigs;Electrophoresis, Polyacrylamide Gel;Animal;Prosencephalon/*cytology/growth &development/*metabolism;Sialic Acids/*metabolism;04 Adult neurogenesis factors;Blotting, Western;Support, Non-U.S. Gov't;Nerve Tissue Protein S 100/*biosynthesis;Male;Cell Movement/physiology}, Number = {2}, Organization = {Department of Anatomy, Faculty of Medicine, Kyushu University, Fukuoka 812-82, Japan. sharif\@anatl.med.kyushu-u.ac.jp}, Pages = {191-205.}, Title = {Expression of NOS, PSA-N-CAM and S100 protein in the granule cell migration pathway of the adult guinea pig forebrain}, Uuid = {0C4F9ECA-ADF5-4052-9D7B-18FE9EB06B6B}, Volume = {107}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9593889%20http://www.elsevier.com:80/cgi-bin/cas/tree/store/bresd/cas_sub/browse/browse.cgi?year=1998&volume=107&issue=2&aid=52483}} @article{Sharma:1999, Abstract = {Cortical epileptic focus was produced by an intracortical injection of FeCl3 in rat cerebral cortex using standard techniques. How after its onset in the cortical focus, the epileptiform activity evolved with time in the thalamus and substantia nigra has been determined. To study the propagation of the epileptiform activity, the local EEG and multiple unit action potentials were recorded from these structures simultaneously with the cortical epileptiform EEG. The results showed that in thalamus and substantia nigra epileptiform activity appeared simultaneously with that in the cortical focus. Intensity of epileptic activity in thalamus and substantia nigra on the whole increased in parallel with that in the cortical focus. The results suggest that the thalamic and nigral epileptiform activity may reinforce the cortical epileptiform activity.}, Author = {Sharma, V. and Singh, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0019-5189}, Journal = {Indian J Exp Biol}, Keywords = {Epilepsy;24 Pubmed search results 2008;Electroencephalography;Research Support, Non-U.S. Gov't;21 Epilepsy;21 Neurophysiology;Rats;Rats, Wistar;Electrophysiology;Male;Thalamus;Animals;Ferric Compounds;Substantia Nigra}, Medline = {99422286}, Month = {5}, Nlm_Id = {0233411}, Number = {5}, Organization = {Neurobiology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.}, Pages = {461-7}, Pubmed = {10492618}, Title = {Electroencephalographic study of iron-induced chronic focal cortical epilepsy in rat: propagation of cortical epileptic activity to substantia nigra and thalamus}, Uuid = {EEE98AAD-E426-40DC-8D8D-D86B07589064}, Volume = {37}, Year = {1999}} @article{Sharma:2000, Abstract = {Modules of neurons sharing a common property are a basic organizational feature of mammalian sensory cortex. Primary visual cortex (V1) is characterized by orientation modules--groups of cells that share a preferred stimulus orientation--which are organized into a highly ordered orientation map. Here we show that in ferrets in which retinal projections are routed into the auditory pathway, visually responsive neurons in 'rewired' primary auditory cortex are also organized into orientation modules. The orientation tuning of neurons within these modules is comparable to the tuning of cells in V1 but the orientation map is less orderly. Horizontal connections in rewired cortex are more patchy and periodic than connections in normal auditory cortex, but less so than connections in V1. These data show that afferent activity has a profound influence on diverse components of cortical circuitry, including thalamocortical and local intracortical connections, which are involved in the generation of orientation tuning, and long-range horizontal connections, which are important in creating an orientation map.}, Author = {Sharma, J. and Angelucci, A. and Sur, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Auditory Cortex;Retina;research support, u.s. gov't, p.h.s. ;Visual Perception;21 Neurophysiology;Ferrets;Vision;Brain Mapping;research support, u.s. gov't, p.h.s.;Animals;Visual Pathways;24 Pubmed search results 2008;Axons}, Month = {4}, Nlm_Id = {0410462}, Number = {6780}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA.}, Pages = {841-7}, Pubmed = {10786784}, Title = {Induction of visual orientation modules in auditory cortex}, Uuid = {87A8625A-93EB-463F-9979-32B1554A9B00}, Volume = {404}, Year = {2000}, url = {papers/Sharma_Nature2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35009043}} @article{Sharp:1986, Author = {Sharp, F. R. and Gonzalez, M. F. and Ferriero, D. M. and Sagar, S. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Research Support, Non-U.S. Gov't;Nerve Regeneration;Motor Cortex;Rats;Research Support, U.S. Gov't, P.H.S.;Research Support, U.S. Gov't, Non-P.H.S.;Dihydrolipoamide Dehydrogenase;Animals;24 Pubmed search results 2008;Neurons;Frontal Lobe}, Medline = {86231562}, Month = {4}, Nlm_Id = {7600130}, Number = {2}, Pages = {204-8}, Pubmed = {3754939}, Title = {Injured adult neocortical neurons sprout fibers into surviving fetal frontal cortex transplants: evidence using NADPH-diaphorase staining}, Uuid = {9730F299-840F-4F29-A9D7-6278A9D88E1C}, Volume = {65}, Year = {1986}} @article{Sharpless:1992, Abstract = {Human immunodeficiency virus type 1 (HIV-1), the agent of AIDS, frequently infects the central nervous system. We inoculated adult human brain cultures with chimeric viruses containing parts of the env gene of a cloned primary isolate from brain tissue, HIV-1 JRFl, inserted into the cloned DNA of a T-cell-tropic strain. A chimeric virus containing the carboxy-terminal portion of HIV-1 JRFl env did not replicate in these brain tissue cultures, while a chimera expressing an env-encoded protein containing 158 amino acids of HIV-1 JRFl gp120, including the V3 loop, replicated well in brain microglial cells, as it does in blood macrophages. Infection of brain microglial cells with such a chimera was blocked by an antibody to the V3 loop of gp 120. Thus, env determinants in the region of gp120, outside the CD4-binding site and comprising the V3 loop, are critical for efficient viral binding to and/or entry into human brain microglia.}, Author = {Sharpless, N. E. and O'Brien, W. A. and Verdin, E. and Kufta, C. V. and Chen, I. S. and Dubois-Dalcq, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Gene Products, env;HIV-1;Humans;Base Sequence;Cells, Cultured;Brain;Antigens, CD4;Kinetics;Recombinant Fusion Proteins;11 Glia;Proviruses;Research Support, U.S. Gov't, P.H.S.;Peptide Fragments;Neuroglia;DNA, Viral;Virus Replication;Molecular Sequence Data;HIV Envelope Protein gp120}, Medline = {92194506}, Month = {4}, Nlm_Id = {0113724}, Number = {4}, Organization = {Laboratory of Viral and Molecular Pathogenesis, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892.}, Pages = {2588-93}, Pubmed = {1548785}, Title = {Human immunodeficiency virus type 1 tropism for brain microglial cells is determined by a region of the env glycoprotein that also controls macrophage tropism}, Uuid = {9DE4B33C-1A3B-4646-A5E1-A15618C69C86}, Volume = {66}, Year = {1992}} @article{Shatry:2004, Abstract = {These studies investigate the involvement of the spleen in progenitor (PC) cell numbers and "cross-talk" with the marrow compartment following syngeneic or allogeneic bone marrow transplantation (BMT) in sham or fully splenectomized mice. Intact recipient B6 mice were lethally irradiated prior to transplant with T cell-depleted bone marrow (BM-TCD).The kinetics of PC reconstitution following i.v. transplant consistently revealed a dramatic increase in splenic colony-forming unit interleukin-3 (CFU IL-3) and CFU (high proliferative potential-(HPP) levels between days 5 and 12 post-BMT. Direct injection of TCD-BM into the recipient marrow cavity did not alter this pattern of reconstitution in the splenic compartment. In contrast to spleens from normal adult B6 mice containing 0.9\%and 0.6\%of the total combined splenic and marrow committed (CFU IL-3) and primitive (CFU-HPP) progenitors, respectively, spleens of syngeneic BMT recipients at day 12 contained a 10-fold increase (p <0.001) over the progenitor levels in normal spleens. These splenic numbers decreased to normal, homeostatic levels by day 28 post-BMT. In contrast, the level of marrow CFU IL-3 progenitors continued to increase post-transplant, reaching near homeostatic levels by day 28 post-BMT. Interestingly, early seeding of 5- (and -6)carboxyfluorescein diacetate succinimidyl ester (CFSE)-labeled or green fluorescent protein (GFP) donor bone marrow cells (BMC) to the marrow compartment was not different in sham splenectomies or recipients splenectomized 14 days earlier. However, recipient splenectomy consistently resulted in significantly higher numbers of CFU IL-3 in the bone marrow during the first 2 weeks post-transplant compared to sham controls. These elevated levels exceeded the combined progenitor numbers of the splenic and marrow compartments of intact recipients. Notably, this increase in marrow progenitor activity in splenectomized recipients was observed after syngeneic as well as allogeneic BMT. Allogeneic transplants across major, or those limited to minor, histocompatibility antigen differences exhibited this increased marrow progenitor activity. Splenectomy performed 2 h post-transplant to assure "normal" marrow seeding also resulted in higher marrow progenitor activity. Thus, this "marrow response" to splenectomy is not induced by early "shunting" of infused BM cells to the marrow compartment. These results suggest that communication between the splenic and marrow compartments following syngeneic and allogeneic BMT exists during early hematopoietic reconstitution, one effect of which is to impact the compartmental distribution of donor progenitor cells. The role of the spleen on engraftment, chimerism, and tolerance in allogeneic BMT models are now under investigation.}, Author = {Shatry, Alwi M. and Jones, Monica and Levy, Robert B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1547-3287}, Journal = {Stem Cells Dev}, Keywords = {Mice, Inbred BALB C;T-Lymphocytes;Animals;Colony-Forming Units Assay;Bone Marrow Transplantation;Female;Interleukin-3;Kinetics;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Time Factors;Male;Bone Marrow;Hematopoiesis;Research Support, U.S. Gov't, P.H.S.;Transplantation, Homologous;Flow Cytometry;Mice;Luminescent Proteins;Stem Cells;Spleen;Research Support, Non-U.S. Gov't}, Month = {2}, Nlm_Id = {101197107}, Number = {1}, Organization = {Department of Microbiology, University of Miami School of Medicine, Miami, FL 33101, USA. Alwi\_shatry\@yahoo.com}, Pages = {51-62}, Pubmed = {15068693}, Title = {The effect of the spleen on compartmental levels and distribution of donor progenitor cells after syngeneic and allogeneic bone marrow transplants}, Uuid = {957BFC8A-90FC-4FB5-8220-174C7D3EF2C7}, Volume = {13}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1089/154732804773099254}} @article{Shaw:2004, Abstract = {Early theories of tumor angiogenesis suggested that preexisting vessels surrounding the tumor were the principal source of the tumor vasculature but recent evidence suggests that endothelial progenitor cells (EPC) migrate from the marrow play an important role in developing the tumor blood supply. In a mouse model, in which the vascularization of a transplantable tumor was studied after bone marrow (BM) transplantation, we show that cells that express Tie-2, Sca-1, CD31 and CD45 function as both BM EPC and primitive hematopoietic stem cells. BM cells from transgenic mice expressing green fluorescent protein (GFP) under the control of the endothelial lineage-specific Tie-2 promoter (Tie-2 /GFP) were used to reconstitute irradiated (12 Gy) wild-type mice. Five donor BM cell populations were studied: (1) whole BM; (2) Sca-1-enriched BMC; (3) GFP/Tie-2+, Sca-1+ BMC; (4) GFP/Tie-2-, Sca-1+ BMC and (5) Sca-1-depleted BMC. After 4 weeks, the mice were injected with Tg.AC tumor cells. Three weeks later, sections from the tumors were stained for CD31 and examined for Tie-2-driven GFP expression. BM-derived endothelial cells were found only in mice transplanted with bone marrow containing populations of Tie-2+, Sca-1+ cells. As few as 3500 of these cells were sufficient to radioprotect lethally irradiated mice. Thus, we conclude that a rare subset of BMC (approximately 4 x 10(-3)\%) with the putative properties of hemangioblasts have an active Tie-2 promoter. Selection of Tie-2+Sca-1+ BMC enriches for marrow-derived EPCs that participate in tumor angiogenesis and cells that can provide hematopoietic reconstitution of marrow-ablated mice.}, Author = {Shaw, J. P. and Basch, R. and Shamamian, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {1079-9796}, Journal = {Blood Cells Mol Dis}, Keywords = {Research Support, Non-U.S. Gov't;Antigens, CD45;Animals;Cell Separation;Bone Marrow Transplantation;Endothelial Cells;Receptor, TIE-2;11 Glia;Green Fluorescent Proteins;Male;Antigens, CD31;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred Strains;Mice;Hematopoietic Stem Cells;Luminescent Proteins;Stem Cells;Neoplasms, Experimental;Promoter Regions (Genetics);Endothelium, Vascular}, Nlm_Id = {9509932}, Number = {1}, Organization = {Department of Surgery, S.A. Localio Laboratory for Surgical Research, New York University School of Medicine, New York, NY 10016, USA.}, Pages = {168-75}, Pii = {S107997960300247X}, Pubmed = {14757432}, Title = {Hematopoietic stem cells and endothelial cell precursors express Tie-2, CD31 and CD45}, Uuid = {E1426B26-DC83-4FE3-AE2A-288B984B8EAF}, Volume = {32}, Year = {2004}} @article{Shearer:2003, Abstract = {Invading meningeal cells form a barrier to axon regeneration after damage to the spinal cord and other parts of the CNS, axons stopping at the interface between meningeal cells and astrocytes. Axon behavior was examined using an in vitro model of astrocyte/meningeal cell interfaces, created by plating aggregates of astrocytes and meningeal cells onto coverslips. At these interfaces growth of dorsal root ganglion axons attempting to grow from astrocytes to meningeal cells was blocked, but axons grew rapidly from meningeal cells onto astrocytes. Meningeal cells were examined for expression of axon growth inhibitory molecules, and found to express NG2, versican, and semaphorins 3A and 3C. Astrocytes express growth promoting molecules, including N-Cadherin, laminin, fibronectin, and tenascin-C. We treated cultures in various ways to attempt to promote axon growth across the inhibitory boundaries. Blockade of NG2 with antibody and blockade of neuropilin 2 but not neuropilin 1 both promoted axon growth from astrocytes to meningeal cells. Blockade of permissive molecules on astrocytes with N-Cadherin blocking peptide or anti beta-1 integrin had no effect. Manipulation of axonal signalling pathways also increased axon growth from astrocytes to meningeal cells. Increasing cAMP levels and inactivation of rho were both effective when the cultures were fixed in paraformaldehyde, demonstrating that their effect is on axons and not via effects on the glial cells. 1044-7431 Journal Article}, Author = {Shearer, M. C. and Niclou, S. P. and Brown, D. and Asher, R. A. and Holtmaat, A. J. and Levine, J. M. and Verhaagen, J. and Fawcett, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {G abstr;11 Glia}, Number = {4}, Organization = {Department of Physiology and Cambridge Centre for Brain Repair, University of Cambridge, Cambridge CB2 3EG, England, UK.}, Pages = {913-25}, Pubmed = {14697658}, Title = {The astrocyte/meningeal cell interface is a barrier to neurite outgrowth which can be overcome by manipulation of inhibitory molecules or axonal signalling pathways}, Uuid = {B476C549-12B5-4D57-A519-8D2A6654BC3C}, Volume = {24}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14697658}} @article{Shechter:2007, Abstract = {Neural stem/progenitor cells are known to exist in the intact spinal cord, but the presence of newly formed neurons during adulthood has not been documented there to date. Here, we report the appearance of newly formed neurons under normal physiological conditions. These neurons are immature, express a GABAergic phenotype, and are primarily located in the dorsal part of the spinal cord. This localization appeared to be mediated by stromal-derived factor-1/CXC-chemokine receptor-4 signaling in the dorsal region. The extent of spinal cord neurogenesis was found to be greatly influenced by immune system integrity and in particular by myelin-specific T cells. These observations provide evidence for in vivo spinal cord neurogenesis under nonpathological conditions and introduce novel mechanisms regulating adult spinal cord plasticity.}, Author = {Shechter, Ravid and Ziv, Yaniv and Schwartz, Michal}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1549-4918}, Journal = {Stem Cells}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {9304532}, Number = {9}, Organization = {Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel.}, Pages = {2277-82}, Pii = {2006-0705}, Pubmed = {17540856}, Title = {New GABAergic interneurons supported by myelin-specific T cells are formed in intact adult spinal cord}, Uuid = {8BAF58DB-200B-4031-9DA0-E4B956E3918B}, Volume = {25}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1634/stemcells.2006-0705}} @article{Sheen:1999, Abstract = {Reconstruction of neocortical circuitry by transplantation of neural precursors, or by manipulation of endogenous precursors, may depend critically upon both local microenvironmental control signals and the intrinsic competence of populations of precursors to appropriately respond to external molecular controls. Dependence on the developmental state of donor or endogenous precursor cells in achieving appropriate differentiation, integration, and connectivity is not clearly understood. Recent studies have demonstrated the ability to generate expandable, often clonal neural precursors at various stages of development. Transplantation of a variety of these precursors suggests that precursor differentiation and integration within the central nervous system (CNS) may depend directly on the level of cellular maturation, with less differentiated, earlier stage precursors offering more flexible but less efficient integration and more differentiated, later stage precursors offering more efficient differentiation to specific phenotypes. To further investigate this hypothesis within neocortex, we used the relatively immature HiB5 multipotent neural precursor cell line derived from embryonic day 16 hippocampus, which is less mature than precursor types that have demonstrated neuronal differentiation in adult neocortex. HiB5 cells labeled fluorescently, radioactively, and genetically were transplanted into murine neocortex under three different conditions expected to offer varying levels of instructive and permissive microenvironmental signals: (1) the developing cortex in utero; (2) regions of adult neocortex undergoing targeted pyramidal neuronal degeneration in which developmental signals are upregulated and in which later stage precursors and immature neurons undergo directed pyramidal neuron differentiation; or (3) the intact adult neocortex. Differentiation and integration of transplanted cells were examined histologically and immunocytochemically by morphology and using neuronal- and glial-specific markers. We found that these precursors underwent differentiation toward cortical neuron phenotypes with characteristic morphologies when transplanted in utero, but failed to do so under either of the adult conditions. HiB5 precursors demonstrated highly immature characteristics in vitro, consistently expressing neuroepithelial but not glial or neuronal markers. Under all conditions, donor cells survived and migrated 1-2 mm from the injection track 2 to 4 weeks after transplantation. HiB5 neural precursors transplanted into the developing cortex of embryonic mice in utero migrated within the cortex, integrated well into the host parenchyma, and differentiated toward morphologically diverse, neuronal phenotypes. HiB5 cells transplanted into the intact cortex of adult mice survived, but did not show neuronal differentiation. In contrast to slightly later stage neural precursors and embryonic neurons used in previous transplantation studies, the HiB5 cells also failed to undergo neuronal differentiation after transplantation into regions undergoing induced apoptotic neuronal degeneration in adult cortex. These results suggested that these early hippocampal-derived precursors might not be fully competent to respond to later stage differentiation and/or survival signals important in neocortex and known to be upregulated in regions undergoing targeted neuronal apoptosis, including the TrkB neurotrophin receptor ligands BDNF and NT-4/5. We investigated this hypothesis and found that undifferentiated HiB5 cells lack catalytic trkB neurotrophin receptors at the mRNA and protein levels, while confirming that they express trkC receptors under the same conditions. Taken together, these findings support a progressive sequence of neural precursor differentiation and a spectrum of competence by precursors to respond to instructive microenvironmental signals. (ABSTRACT TRUNCATED)}, Author = {Sheen, V. L. and Arnold, M. W. and Wang, Y. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Exp Neurol}, Keywords = {Hippocampus/cytology/embryology/transplantation;Tissue Culture;Glial Fibrillary Acidic Protein/genetics;Cells, Cultured;Gene Expression Regulation, Developmental/*genetics;Carrier Proteins/genetics;Phenotype;Female;Animal;C abstr;Brain-Derived Neurotrophic Factor/genetics;Cell Survival/physiology;RNA Precursors/*genetics;Male;Cell Line;Astrocytes/*cytology/*transplantation;Reverse Transcriptase Polymerase Chain Reaction;Mice, Inbred Strains;Blotting, Western;Support, Non-U.S. Gov't;Cell Transplantation;Support, U.S. Gov't, P.H.S.;Neocortex/*cytology/*transplantation;04 Adult neurogenesis factors;Cell Differentiation/physiology;Mice;Cell Movement/physiology}, Number = {1}, Organization = {Division of Neuroscience, Children's Hospital, Boston, Massachusetts, USA.}, Pages = {47-62.}, Title = {Neural precursor differentiation following transplantation into neocortex is dependent on intrinsic developmental state and receptor competence}, Uuid = {D2064BF8-C27A-469C-953D-F0B155AC0212}, Volume = {158}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10448417}} @article{Sheen:2002, Abstract = {Mutations in the X-linked gene Filamin A (FLNA) lead to the human neurological disorder, periventricular heterotopia (PH). Although PH is characterized by a failure in neuronal migration into the cerebral cortex with consequent formation of nodules in the ventricular and subventricular zones, many neurons appear to migrate normally, even in males, suggesting compensatory mechanisms. Here we characterize expression patterns for FlnA and a highly homologous protein Filamin B (FlnB) within the nervous system, in order to better understand their potential roles in cortical development. FlnA mRNA was widely expressed in all cortical layers while FlnB mRNA was most highly expressed in the ventricular and subventricular zones during development. In adulthood, widespread but reduced expression of FlnA and FlnB persisted throughout the cerebral cortex. FlnA and FlnB proteins were highly expressed in both the leading processes and somata of migratory neurons during corticogenesis. Postnatally, FlnA immunoreactivity was largely localized to the cell body with FlnB in the soma and neuropil during neuronal differentiation. In adulthood, diminished expression of both proteins localized to the cell soma and nucleus. Moreover, the putative FLNB homodimerization domain strongly interacted with itself or the corresponding homologous region of FLNA by yeast two-hybrid interaction, the two proteins co-localized within neuronal precursors by immunocytochemistry and the existence of FLNA-FLNB heterodimers could be detected by co-immunoprecipitation. These results suggest that FLNA and FLNB may form both homodimers and heterodimers and that their interaction could potentially compensate for the loss of FLNA function during cortical development within PH individuals.}, Author = {Sheen, Volney L. and Feng, Yuanyi and Graham, Donna and Takafuta, Toshiro and Shapiro, Sandor S. and Walsh, Christopher A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0964-6906}, Journal = {Hum Mol Genet}, Keywords = {Animals;Humans;Gene Expression Regulation, Developmental;Rats;Microfilament Proteins;Immunoenzyme Techniques;21 Epilepsy;Cell Movement;Rats, Sprague-Dawley;Mice, Inbred C57BL;RNA, Messenger;Dimerization;In Situ Hybridization;Research Support, U.S. Gov't, P.H.S.;Saccharomyces cerevisiae;Blotting, Western;21 Neurophysiology;Neurons;Cerebral Cortex;Mice;24 Pubmed search results 2008;Contractile Proteins;Two-Hybrid System Techniques;Precipitin Tests;Research Support, Non-U.S. Gov't}, Medline = {22281257}, Month = {11}, Nlm_Id = {9208958}, Number = {23}, Organization = {Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02115, USA.}, Pages = {2845-54}, Pubmed = {12393796}, Title = {Filamin A and Filamin B are co-expressed within neurons during periods of neuronal migration and can physically interact}, Uuid = {0164F618-8369-477F-9786-067F73F8F18D}, Volume = {11}, Year = {2002}} @article{Shen:2002, Abstract = {Stem cells and neuroblasts derived from mouse embryos undergo repeated asymmetric cell divisions, generating neural lineage trees similar to those of invertebrates. In Drosophila, unequal distribution of Numb protein during mitosis produces asymmetric cell divisions and consequently diverse neural cell fates. We investigated whether a mouse homologue m-numb had a similar role during mouse cortical development. Progenitor cells isolated from the embryonic mouse cortex were followed as they underwent their next cell division in vitro. Numb distribution was predominantly asymmetric during asymmetric cell divisions yielding a beta-tubulin III(-) progenitor and a beta-tubulin III(+) neuronal cell (P/N divisions) and predominantly symmetric during divisions producing two neurons (N/N divisions). Cells from the numb knockout mouse underwent significantly fewer asymmetric P/N divisions compared to wild type, indicating a causal role for Numb. When progenitor cells derived from early (E10) cortex undergo P/N divisions, both daughters express the progenitor marker Nestin, indicating their immature state, and Numb segregates into the P or N daughter with similar frequency. In contrast, when progenitor cells derived from later E13 cortex (during active neurogenesis in vivo) undergo P/N divisions they produce a Nestin(+) progenitor and a Nestin(-) neuronal daughter, and Numb segregates preferentially into the neuronal daughter. Thus during mouse cortical neurogenesis, as in Drosophila neurogenesis, asymmetric segregation of Numb could inhibit Notch activity in one daughter to induce neuronal differentiation. At terminal divisions generating two neurons, Numb was symmetrically distributed in approximately 80\%of pairs and asymmetrically in 20\%. We found a significant association between Numb distribution and morphology: most sisters of neuron pairs with symmetric Numb were similar and most with asymmetric Numb were different. Developing cortical neurons with Numb had longer processes than those without. Numb is expressed by neuroblasts and stem cells and can be asymmetrically segregated by both. These data indicate Numb has an important role in generating asymmetric cell divisions and diverse cell fates during mouse cortical development. 0950-1991 Journal Article}, Author = {Shen, Q. and Zhong, W. and Jan, Y. N. and Temple, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Development}, Keywords = {Support, U.S. Gov't, P.H.S.;10 Development;Neurons/*metabolism;Mice, Knockout;Female;Embryonic Induction;Cell Division;Membrane Proteins/genetics/*metabolism;F;Cerebral Cortex/*cytology/*embryology;Multipotent Stem Cells/*physiology;Cells, Cultured;Animals;Nerve Tissue Proteins/genetics/*metabolism;Mice;Tubulin/metabolism}, Number = {20}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.}, Pages = {4843-53}, Pubmed = {12361975}, Title = {Asymmetric Numb distribution is critical for asymmetric cell division of mouse cerebral cortical stem cells and neuroblasts}, Uuid = {1E264FD2-BAAC-410D-A123-BC0780331AD4}, Volume = {129}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12361975}} @article{Shen:1998, Abstract = {The cytoarchitectural simplicity of the cerebral cortex makes it an attractive system to study central nervous system (CNS) histogenesis--the process whereby diverse cells are generated in the right numbers at the appropriate place and time. Recently, multipotent stem cells have been implicated in this process, as progenitor cells for diverse types of cortical neurons and glia. Continuous analysis of stem cell clone development reveals stereotyped division patterns within their lineage trees, highly reminiscent of neural lineage trees in arthropods and Caenorhabditis elegans. Given that these division patterns play a critical part in generating diverse neural types in invertebrates, we speculate that they play a similar role in the cortex. Because stereotyped lineage trees can be observed from cells growing at clonal density, cell-intrinsic factors are likely to have a key role in stem cell behavior. Cortical stem cells also respond to environmental signals to alter the types of cells they generate, providing the means for feedback regulation on the germinal zone. Evidence is accumulating that cortical stem cells, influenced by intrinsic programs and environmental signals, actually change with development-for example, by reducing the number and types of neurons they produce. Age-related changes in the stem cell population may have a critical role in orchestrating development; whether these cells truly self-renew is a point of discussion. In summary, we propose that cortical stem cells are the focus of regulatory mechanisms central to the development of the cortical cytoarchitecture.}, Author = {Shen, Q. and Qian, X. and Capela, A. and Temple, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Embryo;Cell Line;Stem Cells;Research Support, U.S. Gov't, P.H.S.;22 Stem cells;review, tutorial;Animals;Cerebral Cortex;Neurons;review}, Medline = {98376147}, Month = {8}, Nlm_Id = {0213640}, Number = {2}, Organization = {Albany Medical College, New York 12208-3479, USA.}, Pages = {162-74}, Pii = {10.1002/(SICI)1097-4695(199808)36:2<162::AID-NEU5>3.0.CO;2-#}, Pubmed = {9712302}, Title = {Stem cells in the embryonic cerebral cortex: their role in histogenesis and patterning}, Uuid = {9D439A13-55CE-4681-989D-845052DC54B3}, Volume = {36}, Year = {1998}, url = {papers/Shen_JNeurobiol1998.pdf}} @article{Shen:2006, Abstract = {In the developing cerebral cortex, neurons are born on a predictable schedule. Here we show in mice that the essential timing mechanism is programmed within individual progenitor cells, and its expression depends solely on cell-intrinsic and environmental factors generated within the clonal lineage. Multipotent progenitor cells undergo repeated asymmetric divisions, sequentially generating neurons in their normal in vivo order: first preplate cells, including Cajal-Retzius neurons, then deep and finally superficial cortical plate neurons. As each cortical layer arises, stem cells and neuroblasts become restricted from generating earlier-born neuron types. Growth as neurospheres or in co-culture with younger cells did not restore their plasticity. Using short-hairpin RNA (shRNA) to reduce Foxg1 expression reset the timing of mid- but not late-gestation progenitors, allowing them to remake preplate neurons and then cortical-plate neurons. Our data demonstrate that neural stem cells change neuropotency during development and have a window of plasticity when restrictions can be reversed.}, Author = {Shen, Qin and Wang, Yue and Dimos, John T. and Fasano, Christopher A. and Phoenix, Timothy N. and Lemischka, Ihor R. and Ivanova, Natalia B. and Stifani, Stefano and Morrisey, Edward E. and Temple, Sally}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.}, Pages = {743-51}, Pii = {nn1694}, Pubmed = {16680166}, Title = {The timing of cortical neurogenesis is encoded within lineages of individual progenitor cells}, Uuid = {A73408F1-7BDC-4A94-A5D6-BAB27BABAE09}, Volume = {9}, Year = {2006}, url = {papers/Shen_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1694}} @article{Shen:1984, Abstract = {The neurological reactions in Wallerian degeneration have been studied by electron microscopy in the optic nerve of adult albino rats from 7 to 120 days after unilateral enucleation. Reactive astrocytes contained abundant dense bodies, numerous microtubules and hyperplastic glial filaments. These astrocytes also assisted phagocytosis of degenerated myelin sheaths and in glial scar formation. Oligodendrocytes disconnected their cytoplasmic extensions, which were phagocytosed by microglial cells and astrocytes, by increased production of lysosomes. Microglial cells consisted of crinkled, long, rough endoplasmic reticula, several highly-active Golgi complexes, laminar inclusions and globoid lipid droplets. Microglia engulfed and lysed the disintegrated axons and myelin sheaths.}, Author = {Shen, C. L. and Liu, K. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {0255-6596}, Journal = {Proc Natl Sci Counc Repub China B}, Keywords = {Neuroglia;Wallerian Degeneration;Nerve Degeneration;Rats;Microscopy, Electron;Astrocytes;Postoperative Complications;Ophthalmologic Surgical Procedures;Not relevant;11 Glia;Optic Nerve;Animals;Oligodendroglia;Support, Non-U.S. Gov't;Phagocytosis}, Medline = {87261528}, Month = {10}, Nlm_Id = {8502426}, Number = {4}, Pages = {324-34}, Pubmed = {6571594}, Title = {Neuroglia of the adult rat optic nerve in the course of wallerian degeneration}, Uuid = {62AFA50A-D1E1-45DB-929E-E54585032A44}, Volume = {8}, Year = {1984}} @article{Shen:2004, Abstract = {Neural stem cells are reported to lie in a vascular niche, but there is no direct evidence for a functional relationship between the stem cells and blood vessel component cells. We show that endothelial cells but not vascular smooth muscle cells release soluble factors that stimulate the self-renewal of neural stem cells, inhibit their differentiation, and enhance their neuron production. Both embryonic and adult neural stem cells respond, allowing extensive production of both projection neuron and interneuron types in vitro. Endothelial coculture stimulates neuroepithelial cell contact, activating Notch and Hes 1 to promote self-renewal. These findings identify endothelial cells as a critical component of the neural stem cell niche.}, Author = {Shen, Qin and Goderie, Susan K. and Jin, Li and Karanth, Nithin and Sun, Yu and Abramova, Natalia and Vincent, Peter and Pumiglia, Kevin and Temple, Sally}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Cell Differentiation;Signal Transduction;Astrocytes;Animals;Cells, Cultured;Endothelial Cells;Oligodendroglia;Cell Communication;Fibroblast Growth Factor 2;Embryo;03 Adult neurogenesis progenitor source;Cell Line;Cell Lineage;Coculture;Cerebral Cortex;Neurons;Cattle;Cell Adhesion;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Muscle, Smooth, Vascular;Stem Cells;Clone Cells;Myocytes, Smooth Muscle;Endothelium, Vascular}, Month = {5}, Nlm_Id = {0404511}, Number = {5675}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, NY 12208, USA.}, Pages = {1338-40}, Pii = {1095505}, Pubmed = {15060285}, Title = {Endothelial cells stimulate self-renewal and expand neurogenesis of neural stem cells}, Uuid = {3B051C69-009A-4A6F-8430-9366D36D453E}, Volume = {304}, Year = {2004}, url = {papers/Shen_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1095505}} @article{Sheng:2003, Author = {Sheng, Morgan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {18 Classic Neuroanatomy Physiology;Neurobiology;review literature;Human;Publishing;Animals;Support, Non-U.S. Gov't;Nervous System Diseases;Neurons;review}, Medline = {22919818}, Month = {10}, Nlm_Id = {8809320}, Number = {2}, Organization = {The Picower Center for Learning and Memory, Howard Hughes Medical Institute, RIKEN-MIT Neuroscience Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. msheng\@mit.edu}, Pages = {193-7}, Pii = {S0896627303006421}, Pubmed = {14556703}, Title = {15 years of neuron cell biology}, Uuid = {E7990DA2-47DF-4424-8B23-40E6B02A5A0D}, Volume = {40}, Year = {2003}, url = {papers/Sheng_Neuron2003.pdf}} @article{Shepherd:2005, Abstract = {Can neuronal morphology predict functional synaptic circuits? In the rat barrel cortex, 'barrels' and 'septa' delineate an orderly matrix of cortical columns. Using quantitative laser scanning photostimulation we measured the strength of excitatory projections from layer 4 (L4) and L5A to L2/3 pyramidal cells in barrel- and septum-related columns. From morphological reconstructions of excitatory neurons we computed the geometric circuit predicted by axodendritic overlap. Within most individual projections, functional inputs were predicted by geometry and a single scale factor, the synaptic strength per potential synapse. This factor, however, varied between projections and, in one case, even within a projection, up to 20-fold. Relationships between geometric overlap and synaptic strength thus depend on the laminar and columnar locations of both the pre- and postsynaptic neurons, even for neurons of the same type. A large plasticity potential appears to be incorporated into these circuits, allowing for functional 'tuning' with fixed axonal and dendritic arbor geometry.}, Author = {Shepherd, Gordon M. G. and Stepanyants, Armen and Bureau, Ingrid and Chklovskii, Dmitri and Svoboda, Karel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, non-u.s. gov't ;24 Pubmed search results 2008;Lysine;Animals;Photic Stimulation;research support, u.s. gov't, p.h.s. ;Ultraviolet Rays;Synaptic Transmission;research support, n.i.h., extramural;Organ Culture Techniques;Electric Stimulation;Brain Mapping;Synapses;research support, n.i.h., extramural ;research support, u.s. gov't, p.h.s.;Dendrites;21 Circuit structure-function;Neural Pathways;Neuronal Plasticity;Axons;Image Cytometry;Pyramidal Cells;Rats, Sprague-Dawley;Lasers;Rats;research support, non-u.s. gov't;21 Neurophysiology;Somatosensory Cortex;Cell Shape;Excitatory Postsynaptic Potentials}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {Howard Hughes Medical Institute, Cold Spring Harbor, New York 11724, USA.}, Pages = {782-90}, Pii = {nn1447}, Pubmed = {15880111}, Title = {Geometric and functional organization of cortical circuits}, Uuid = {0C6F372D-EFED-45CD-B70A-5DAF67BF7C14}, Volume = {8}, Year = {2005}, url = {papers/Shepherd_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1447}} @article{Sherwood:2006, Abstract = {Evidence from comparative studies of gene expression and evolution suggest that human neocortical neurons may be characterized by unusually high levels of energy metabolism. The current study examined whether there is a disproportionate increase in glial cell density in the human frontal cortex in comparison with other anthropoid primate species (New World monkeys, Old World monkeys, and hominoids) to support greater metabolic demands. Among 18 species of anthropoids, humans displayed the greatest departure from allometric scaling expectations for the density of glia relative to neurons in layer II/III of dorsolateral prefrontal cortex (area 9L). However, the human glia-neuron ratio in this prefrontal region did not differ significantly from allometric predictions based on brain size. Further analyses of glia-neuron ratios across frontal areas 4, 9L, 32, and 44 in a sample of humans, chimpanzees, and macaque monkeys showed that regions involved in specialized human cognitive functions, such as "theory of mind" (area 32) and language (area 44) have not evolved differentially higher requirements for metabolic support. Taken together, these findings suggest that greater metabolic consumption of human neocortical neurons relates to the energetic costs of maintaining expansive dendritic arbors and long-range projecting axons in the context of an enlarged brain.}, Author = {Sherwood, Chet C. and Stimpson, Cheryl D. and Raghanti, Mary Ann and Wildman, Derek E. and Uddin, Monica and Grossman, Lawrence I. and Goodman, Morris and Redmond, John C. and Bonar, Christopher J. and Erwin, Joseph M. and Hof, Patrick R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Frontal Lobe;Neurons;19 Neocortical evolution;Neuroglia;research support, n.i.h., extramural ;research support, non-u.s. gov't ;Pan troglodytes;Cell Count;Organ Size;research support, u.s. gov't, non-p.h.s. ;Evolution;Animals;Brain;24 Pubmed search results 2008;Humans;Macaca}, Month = {9}, Nlm_Id = {7505876}, Number = {37}, Organization = {Department of Anthropology, The George Washington University, Washington, DC 20052, USA. sherwood\@gwu.edu}, Pages = {13606-11}, Pii = {0605843103}, Pubmed = {16938869}, Title = {Evolution of increased glia-neuron ratios in the human frontal cortex}, Uuid = {920D6E0F-28F5-44FF-989C-43A9D6743568}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0605843103}} @article{Shetty:1998, Abstract = {Neural stem cells proliferate in vitro and form neurospheres in the presence of epidermal growth factor (EGF), and are capable of differentiating into both neurons and glia when exposed to a substrate. We hypothesize that specific neurotrophic factors induce differentiation of stem cells from different central nervous system (CNS) regions into particular fates. We investigated differentiation of stem cells from the postnatal mouse hippocampus in culture using the following trophic factors (20 ng/mL): brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and glial-derived neurotrophic factor (GDNF). Without trophic factors, 32\%of stem cells differentiated into neurons by 4 days in vitro (DIV), decreasing to 10\%by 14 DIV. Addition of BDNF (starting at either day 0 or day 3) significantly increased neuron survival (31-43\%by 14 DIV) and differentiation. Morphologically, many well-differentiated neurons resembled hippocampal pyramidal neurons. 5'-Bromodeoxyuridine labeling demonstrated that the pyramidal-like neurons originated from stem cells which had proliferated in EGF-containing cultures. However, similar application of NT-3 and GDNF did not exert such a differentiating effect. Addition of BDNF to stem cells from the postnatal cerebellum, midbrain, and striatum did not induce these neuronal phenotypes, though similar application to cortical stem cells yielded pyramidal-like neurons. Thus, BDNF supports survival of hippocampal stem cell-derived neurons and also can induce differentiation of these cells into pyramidal-like neurons. The presence of pyramidal neurons in BDNF-treated hippocampal and cortical stem cell cultures, but not in striatal, cerebellar, and midbrain stem cell cultures, suggests that stem cells from different CNS regions differentiate into region-specific phenotypic neurons when stimulated with an appropriate neurotrophic factor.}, Author = {Shetty, A. K. and Turner, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Neurons;Cell Differentiation;Hippocampus;Epidermal Growth Factor;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Cell Line;Cell Survival;Animals, Newborn;Research Support, U.S. Gov't, Non-P.H.S.;Brain-Derived Neurotrophic Factor;Mice;Animals;24 Pubmed search results 2008;Cells, Cultured;Mice, Inbred Strains}, Medline = {98287718}, Month = {6}, Nlm_Id = {0213640}, Number = {4}, Organization = {Department of Surgery (Neurosurgery) and Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA. ashok.shetty\@duke.edu}, Pages = {395-425}, Pii = {10.1002/(SICI)1097-4695(19980615)35:4<395::AID-NEU7>3.0.CO;2-U}, Pubmed = {9624622}, Title = {In vitro survival and differentiation of neurons derived from epidermal growth factor-responsive postnatal hippocampal stem cells: inducing effects of brain-derived neurotrophic factor}, Uuid = {4A58599D-CE28-442B-AF7A-F045F4F06758}, Volume = {35}, Year = {1998}} @article{Shibata:1997, Abstract = {The glutamate transporter GLAST is localized on the cell membrane of mature astrocytes and is also expressed in the ventricular zone of developing brains. To characterize and follow the GLAST-expressing cells during development, we examined the mouse spinal cord by in situ hybridization and immunohistochemistry. At embryonic day (E) 11 and E13, cells expressing GLAST mRNA were present only in the ventricular zone, where GLAST immunoreactivity was associated with most of the cell bodies of neuroepithelial cells. In addition, GLAST immunoreactivity was detected in radial processes running through the mantle and marginal zones. From this characteristic cytology, GLAST-expressing cells at early stages were judged to be radial glia cells. At E15, cells expressing GLAST mRNA first appeared in the mantle zone, and GLAST-immunopositive punctate or reticular protrusions were formed along the radial processes. From E18 to postnatal day (P) 7, GLAST mRNA or its immunoreactivity gradually decreased from the ventricular zone and disappeared from radial processes, whereas cells with GLAST mRNA spread all over the mantle zone and GLAST-immunopositive punctate/reticular protrusions predominated in the neuropils. At P7, GLAST-expressing cells were immunopositive for glial fibrillary acidic protein, an intermediate filament specific to astrocytes. Therefore, the glutamate transporter GLAST is expressed from radial glia through astrocytes during spinal cord development. Furthermore, the distinct changes in the cell position and morphology suggest that both the migration and transformation of radial glia cells begin in the spinal cord between E13 and E15, when the active stage of neuronal migration is over.}, Author = {Shibata, T. and Yamada, K. and Watanabe, M. and Ikenaka, K. and Wada, K. and Tanaka, K. and Inoue, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci}, Keywords = {Spinal Cord/cytology/embryology/*metabolism;RNA, Messenger/biosynthesis;G;Neuroglia/*metabolism;Nerve Tissue Proteins/*metabolism;*Gene Expression Regulation, Developmental;ABC Transporters/*biosynthesis/genetics;Glial Fibrillary Acidic Protein/analysis;Astrocytes/metabolism;Animal;11 Glia;Mice, Inbred C57BL;Cell Movement;Support, Non-U.S. Gov't;Cell Lineage;Mice;Amino Acid Sequence;Molecular Sequence Data;Gestational Age}, Number = {23}, Organization = {Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060, Japan.}, Pages = {9212-9.}, Title = {Glutamate transporter GLAST is expressed in the radial glia-astrocyte lineage of developing mouse spinal cord}, Uuid = {2FB65D68-F4EE-42CE-A85D-3F4F46237375}, Volume = {17}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9364068}} @article{Shieh:1998, Abstract = {The role of human immunodeficiency virus (HIV) strain variability remains a key unanswered question in HIV dementia, a condition affecting around 20\%of infected individuals. Several groups have shown that viruses within the central nervous system (CNS) of infected patients constitute an independently evolving subset of HIV strains. A potential explanation for the replication and sequestration of viruses within the CNS is the preferential use of certain chemokine receptors present in microglia. To determine the role of specific chemokine coreceptors in infection of adult microglial cells, we obtained a small panel of HIV type 1 brain isolates, as well as other HIV strains that replicate well in cultured microglial cells. These viruses and molecular clones of their envelopes were used in infections, in cell-to-cell fusion assays, and in the construction of pseudotypes. The results demonstrate the predominant use of CCR5, at least among the major coreceptors, with minor use of CCR3 and CXCR4 by some of the isolates or their envelope clones.}, Author = {Shieh, J. T. and Albright, A. V. and Sharron, M. and Gartner, S. and Strizki, J. and Doms, R. W. and Gonz{\'a}lez-Scarano, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Tumor Cells, Cultured;Transfection;HIV-1;Receptors, CCR5;Research Support, Non-U.S. Gov't;Adult;Membrane Fusion;Virus Replication;Research Support, U.S. Gov't, P.H.S.;Cytopathogenic Effect, Viral;11 Glia;Microglia;Cells, Cultured;Receptors, CXCR4;Brain;Receptors, Chemokine;Humans}, Medline = {98216792}, Month = {5}, Nlm_Id = {0113724}, Number = {5}, Organization = {Department of Neurology, University of Pennsylvania Medical Center, Philadelphia 19104-6146, USA.}, Pages = {4243-9}, Pubmed = {9557714}, Title = {Chemokine receptor utilization by human immunodeficiency virus type 1 isolates that replicate in microglia}, Uuid = {8914F6A6-8EBD-4ACA-B4BB-7C54DE0E8A37}, Volume = {72}, Year = {1998}, url = {papers/Shieh_JVirol1998.pdf}} @article{Shieh:2000, Abstract = {Microglia are the main reservoir for human immunodeficiency virus type 1 (HIV-1) in the central nervous system (CNS), and multinucleated giant cells, the result of fusion of HIV-1-infected microglia and brain macrophages, are the neuropathologic hallmark of HIV dementia. One potential explanation for the formation of syncytia is viral adaptation for these CD4(+) CNS cells. HIV-1(BORI-15), a virus adapted to growth in microglia by sequential passage in vitro, mediates high levels of fusion and replicates more efficiently in microglia and monocyte-derived-macrophages than its unpassaged parent (J. M. Strizki, A. V. Albright, H. Sheng, M. O'Connor, L. Perrin, and F. Gonzalez-Scarano, J. Virol. 70:7654-7662, 1996). Since the interaction between the viral envelope glycoprotein and CD4 and the chemokine receptor mediates fusion and plays a key role in tropism, we have analyzed the HIV-1(BORI-15) env as a fusogen and in recombinant and pseudotyped viruses. Its syncytium-forming phenotype is not the result of a switch in coreceptor use but rather of the HIV-1(BORI-15) envelope-mediated fusion of CD4(+)CCR5(+) cells with greater efficiency than that of its parental strain, either by itself or in the context of a recombinant virus. Genetic analysis indicated that the syncytium-forming phenotype was due to four discrete amino acid differences in V1/V2, with a single-amino-acid change between the parent and the adapted virus (E153G) responsible for the majority of the effect. Additionally, HIV-1(BORI-15) env-pseudotyped viruses were less sensitive to decreases in the levels of CD4 on transfected 293T cells, leading to the hypothesis that the differences in V1/V2 alter the interaction between this envelope and CD4 or CCR5, or both. In sum, the characterization of the envelope of HIV-1(BORI-15), a highly fusogenic glycoprotein with genetic determinants in V1/V2, may lead to a better understanding of the relationship between HIV replication and syncytium formation in the CNS and of the importance of this region of gp120 in the interaction with CD4 and CCR5.}, Author = {Shieh, J. T. and Mart{\'\i}n, J. and Baltuch, G. and Malim, M. H. and Gonz{\'a}lez-Scarano, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Gene Products, env;Human;HIV-1;Cells, Cultured;Humans;Phenotype;Cell Line, Transformed;Microglia;Cell Fusion;Antigens, CD4;11 Glia;Giant Cells;Leukocytes, Mononuclear;Research Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Tumor Cells, Cultured;Recombination, Genetic;Adult;Support, U.S. Gov't, P.H.S.;Receptors, CCR5;Virus Replication;Chromosome Mapping;Research Support, Non-U.S. Gov't}, Medline = {20091324}, Month = {1}, Nlm_Id = {0113724}, Number = {2}, Organization = {Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania, USA.}, Pages = {693-701}, Pubmed = {10623731}, Title = {Determinants of syncytium formation in microglia by human immunodeficiency virus type 1: role of the V1/V2 domains}, Uuid = {12B98C7C-433A-11DB-A5D2-000D9346EC2A}, Volume = {74}, Year = {2000}, url = {papers/Shieh_JVirol2000.pdf}} @article{Shigematsu:1992, Abstract = {Kainic acid lesions of rat striatum caused an elevation of amyloid precursor protein (APP) immunoreactivity in neurons and neurites, some of which were then phagocytosed by reactive microglia/macrophages. Immunoexpression of APP was observed in neurites and neurons 1 day after the kainic injection. Four days after lesioning, immunoreactivity was still concentrated in thick and distorted neurites, but it began to appear in microglia/macrophages and in the tissue matrix. The cells were identified as microglia/macrophages by the phenotypic markers Ia (OX6), leukocyte common antigen (OX1), C3bi receptor (OX42), and macrophage marker (ED1). They were negative for the astrocytic marker glial fibrillary acidic protein (GFAP). APP immunoreactivity in these phagocytic cells was most prominent between 1 week and 1 month postlesioning. No extracellular amyloid fibrils were detectable. These results suggest that APP production is rapidly upregulated in damaged neurons and accumulates in degenerating axons. However, phagocytosis of APP by reactive microglia/macrophages in this rat model does not result in production of Alzheimer type amyloid deposits.}, Author = {Shigematsu, K. and McGeer, P. L. and Walker, D. G. and Ishii, T. and McGeer, E. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Phagocytosis;Animals;Macrophages;Rats;Nervous System Diseases;Axons;Rats, Inbred Strains;Neurites;Not relevant;11 Glia;Kainic Acid;Antibodies;Amyloid beta-Protein Precursor;Male;Support, Non-U.S. Gov't;Neurons;Neuroglia;Perfusion;Amino Acid Sequence;Molecular Sequence Data}, Medline = {92349469}, Month = {3}, Nlm_Id = {7600111}, Number = {3}, Organization = {Kinsmen Laboratory of Neurological Research, Department of Psychiatry, University of British Columbia, Vancouver, Canada.}, Pages = {443-53}, Pubmed = {1640496}, Title = {Reactive microglia/macrophages phagocytose amyloid precursor protein produced by neurons following neural damage}, Uuid = {08CB9713-521C-4AC3-B50C-1990938B467D}, Volume = {31}, Year = {1992}} @article{Shih:2006, Author = {Shih, Andy Y. and Fernandes, Herman B. and Choi, Fiona Y. and Kozoriz, Michael G. and Liu, Yingru and Li, Ping and Cowan, Catherine M. and Klegeris, Andis}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {comment;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {15}, Organization = {Graduate Program in Neuroscience, University of British Columbia, Vancouver, British Columbia, V6T 1Z3, Canada. ashih\@interchange.ubc.ca}, Pages = {3887-8}, Pii = {26/15/3887}, Pubmed = {16611803}, Title = {Policing the police: astrocytes modulate microglial activation}, Uuid = {9B6294E5-D3CC-4BEC-BC59-F83659A08311}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0936-06.2006}} @article{Shihabuddin:1997, Abstract = {The adult rat brain contains progenitor cells that can be induced to proliferate in vitro in response to FGF-2. In the present study we explored whether similar progenitor cells can be cultured from different levels (cervical, thoracic, lumbar, and sacral) of adult rat spinal cord and whether they give rise to neurons and glia as well as spinal cord-specific neurons (e.g., motoneurons). Cervical, thoracic, lumbar, and sacral areas of adult rat spinal cord (>3 months old) were microdissected and neural progenitors were isolated and cultured in serum-free medium containing FGF-2 (20 ng/ml) through multiple passages. Although all areas generated rapidly proliferating cells, the cultures were heterogeneous in nature and cell morphology varied within a given area as well as between areas. A percentage of cells from all areas of the spinal cord differentiate into cells displaying antigenic properties of neuronal, astroglial, and oligodendroglial lineages; however, the majority of cells from all regions expressed the immature proliferating progenitor marker vimentin. In established multipassage cultures, a few large, neuron-like cells expressed immunoreactivity for p75NGFr and did not express GFAP. These cells may be motoneurons. These results demonstrate that FGF-2 is mitogenic for progenitor cells from adult rat spinal cord that have the potential to give rise to glia and neurons including motoneurons.}, Author = {Shihabuddin, L. S. and Ray, J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {Exp Neurol}, Keywords = {Rats;Female;Animal;02 Adult neurogenesis migration;Glial Fibrillary Acidic Protein/analysis;Stem Cells/*cytology/drug effects;Spinal Cord/*cytology/growth &development;Fibroblast Growth Factor, Basic/*pharmacology;Neuroglia/*cytology/drug effects;03 Adult neurogenesis progenitor source;Rats, Inbred F344;BB abstr;Support, Non-U.S. Gov't;Organ Specificity;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Neurons/*cytology/drug effects;Cell Division/drug effects}, Number = {2}, Organization = {Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {577-86.}, Title = {FGF-2 is sufficient to isolate progenitors found in the adult mammalian spinal cord}, Uuid = {9DF363D5-B190-4B9A-B25D-73F1B3E2556C}, Volume = {148}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9417834}} @article{Shihabuddin:1995, Abstract = {The chronic survival and differentiation of the conditionally immortalized neuronal cell line, RN33B, was examined following transplantation into the adult and neonatal rat hippocampus and cerebral cortex. In clonal culture, differentiated RN33B cells express p75NTR and trkB mRNA and protein, and respond to brain-derived neurotrophic factor treatment by inducing c-fos mRNA. Transplanted cells, identified using immunohistochemistry to detect beta-galactosidase expression, were seen in most animals up to 24 weeks posttransplantation (the latest time point examined). Stably integrated cells with various morphologies consistent with their transplantation site were observed. In the cerebral cortex, many RN33B cells differentiated with morphologies similar to pyramidal neurons and stellate cells. In the hippocampal formation, many RN33B cells assumed morphologies similar to pyramidal neurons characteristic of CA1 and CA3 regions, granular cell layer neurons of the dentate gyrus, and polymorphic neurons of the hilar region. Identical morphologies were observed in both adult and neonatal hosts, although a greater percentage of beta-galactosidase immunoreactive cells had differentiated in the neonatal brains. These results suggest that RN33B cells have the developmental plasticity to respond to local microenvironmental signals and that the adult brain retains the capacity to direct the differentiation of neuronal precursor cells in a direction that is consistent with that of endogenous neurons. eng Journal Article}, Author = {Shihabuddin, L. S. and Hertz, J. A. and Holets, V. R. and Whittemore, S. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Journal = {J Neurosci}, Keywords = {Cell Survival;Cell Differentiation;Rats, Inbred Lew;Rats;Neurons/*cytology/enzymology/*transplantation;Cell Line, Transformed;beta-Galactosidase/metabolism;Aging/physiology;Female;Animal;Stem Cells/*cytology/enzymology/*transplantation;17 Transplant Regeneration;Time Factors;Hippocampus/*physiology;Animals, Newborn;Support, Non-U.S. Gov't;L abstr;Support, U.S. Gov't, P.H.S.;Cerebral Cortex/*physiology}, Number = {10}, Organization = {Neuroscience Program, University of Miami School of Medicine, Florida 33136, USA.}, Pages = {6666-78.}, Title = {The adult CNS retains the potential to direct region-specific differentiation of a transplanted neuronal precursor cell line}, Uuid = {D0081226-FB61-44C2-841C-F48FA20236A3}, Volume = {15}, Year = {1995}} @article{Shihabuddin:2000, Abstract = {The adult rat spinal cord contains cells that can proliferate and differentiate into astrocytes and oligodendroglia in situ. Using clonal and subclonal analyses we demonstrate that, in contrast to progenitors isolated from the adult mouse spinal cord with a combination of growth factors, progenitors isolated from the adult rat spinal cord using basic fibroblast growth factor alone display stem cell properties as defined by their multipotentiality and self-renewal. Clonal cultures derived from single founder cells generate neurons, astrocytes, and oligodendrocytes, confirming the multipotent nature of the parent cell. Subcloning analysis showed that after serial passaging, recloning, and expansion, these cells retained multipotentiality, indicating that they are self-renewing. Transplantation of an in vitro-expanded clonal population of cells into the adult rat spinal cord resulted in their differentiation into glial cells only. However, after heterotopic transplantation into the hippocampus, transplanted cells that integrated in the granular cell layer differentiated into cells characteristic of this region, whereas engraftment into other hippocampal regions resulted in the differentiation of cells with astroglial and oligodendroglial phenotypes. The data indicate that clonally expanded, multipotent adult progenitor cells from a non- neurogenic region are not lineage-restricted to their developmental origin but can generate region-specific neurons in vivo when exposed to the appropriate environmental cues.}, Author = {Shihabuddin, L. S. and Horner, P. J. and Ray, J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:56:59 -0400}, Journal = {J Neurosci}, Keywords = {Stem Cells/drug effects/*transplantation;Cell Differentiation;Fibroblast Growth Factor, Basic/pharmacology;Clone Cells/transplantation;Cells, Cultured;Hippocampus/cytology/surgery;Rats;Neurons/*cytology;Dentate Gyrus/*cytology/surgery;Phenotype;Animal;02 Adult neurogenesis migration;Transplantation, Heterotopic;Spinal Cord/*cytology/*transplantation;Neck;Support, Non-U.S. Gov't;Cell Lineage;B;Support, U.S. Gov't, P.H.S.;Immunohistochemistry;Graft Survival;Bromodeoxyuridine;Neuroglia/cytology}, Number = {23}, Organization = {The Salk Institute, Laboratory of Genetics, La Jolla, California 92037, USA.}, Pages = {8727-35.}, Title = {Adult spinal cord stem cells generate neurons after transplantation in the adult dentate gyrus}, Uuid = {E19753CA-98F3-4AD6-B196-4C5FAB2E6F0A}, Volume = {20}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11102479%20http://www.jneurosci.org/cgi/content/full/20/23/8727%20http://www.jneurosci.org/cgi/content/abstract/20/23/8727}} @article{Shima:2007, Abstract = {The growth of neurites (axon and dendrite) should be appropriately regulated by their interactions in the development of nervous systems where a myriad of neurons and their neurites are tightly packed. We show here that mammalian seven-pass transmembrane cadherins Celsr2 and Celsr3 are activated by their homophilic interactions and regulate neurite growth in an opposing manner. Both gene-silencing and coculture assay with rat neuron cultures showed that Celsr2 enhanced neurite growth, whereas Celsr3 suppressed it, and that their opposite functions were most likely the result of a difference of a single amino acid residue in the transmembrane domain. Together with calcium imaging and pharmacological analyses, our results suggest that Celsr2 and Celsr3 fulfill their functions through second messengers, and that differences in the activities of the homologs results in opposite effects in neurite growth regulation.}, Author = {Shima, Yasuyuki and Kawaguchi, Shin-ya Y. and Kosaka, Kazuyoshi and Nakayama, Manabu and Hoshino, Mikio and Nabeshima, Yoichi and Hirano, Tomoo and Uemura, Tadashi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Dose-Response Relationship, Drug;Animals;Cloning, Molecular;Humans;Rats;Transfection;Cell Line, Transformed;Mutation;Neurites;Culture Media, Conditioned;Hippocampus;research support, non-u.s. gov't;Calcium;RNA, Small Interfering;Receptors, G-Protein-Coupled;Cadherins;Neurons;24 Pubmed search results 2008;Cell Enlargement;in vitro}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Graduate School of Biostudies, Yoshida Konoecho, Kyoto University, Kyoto, Kyoto 606-8501, Japan.}, Pages = {963-9}, Pii = {nn1933}, Pubmed = {17618280}, Title = {Opposing roles in neurite growth control by two seven-pass transmembrane cadherins}, Uuid = {13FBE197-2D28-4F06-A3AB-62E2E9C7E944}, Volume = {10}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1933}} @article{Shimada:1996, Abstract = {Various cortical dysplasias, such as agyria-lissencephalia, pachygyria, micropolygyria, neuronal heterotopia and so on, have become relatively common neuropathological findings among the children with intactable epilepsy and mental and/or physical handicap. Together with various environmental factors, gene abnormalities are recently increasing as a cause in various cortical dysplasias. However, details of the pathogenesis still remain unknown. Experimental studies using animal models indicated that inhibition of neuron production, disorders of neuron-glia and neuron-neuron contact, and plastic and unbalanced synaptogenesis subsequent to abnormal neuron production play an important role either separately or in combination in the pathogenesis of various cortical dysplasias.}, Author = {Shimada, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0029-0831}, Journal = {No To Hattatsu}, Keywords = {21 Epilepsy;24 Pubmed search results 2008;21 Neurophysiology;English Abstract;Animals;Humans;Brain;review;Abnormalities}, Medline = {97003966}, Month = {3}, Nlm_Id = {0215224}, Number = {2}, Organization = {Department of Pediatrics, Shiga University of Medical Science, Otsu.}, Pages = {93-101}, Pubmed = {8851277}, Title = {[Chaos in pathogenesis of brain dysgenesis]}, Uuid = {427C05E9-0B3C-4579-BA3F-CAAC3AA315E7}, Volume = {28}, Year = {1996}} @article{Shimazaki:2001, Abstract = {The cytokines that signal through the common receptor subunit gp130, including ciliary neurotrophic factor (CNTF), interleukin-6, leukemia inhibitory factor (LIF) and oncostatin M, have pleiotropic functions in CNS development. Given the restricted expression domain of the CNTF receptor alpha (CNTFR) in the developing forebrain germinal zone and adult forebrain periventricular area, we have examined the putative role of CNTFR/LIFR/gp130-mediated signaling in regulating forebrain neural stem cell fate in vivo and in vitro. Analysis of LIFR-deficient mice revealed that a decreased level of LIFR expression results in a reduction in the number of adult neural stem cells. In adult LIFR heterozygote (+/-) mice, the number of neural stem cells and their progeny in the forebrain subependyma and TH-immunoreactive neurons in the olfactory bulb were significantly reduced. Intraventricular infusion of CNTF into the adult mouse forebrain, in the absence or presence of epidermal growth factor (EGF), enhanced self-renewal of neural stem cells in vivo. Analyses of EGF-responsive neural stem cells proliferating in vitro found that CNTF inhibits lineage restriction of neural stem cells to glial progenitors, which in turn results in enhanced expansion of stem cell number. These results suggest that CNTFR/LIFR/gp130-mediated signaling supports the maintenance of forebrain neural stem cells, likely by suppressing restriction to a glial progenitor cell fate.}, Author = {Shimazaki, T. and Shingo, T. and Weiss, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurosci}, Keywords = {Cell Differentiation/drug effects;Heterozygote;Receptor, Ciliary Neurotrophic Factor/genetics/*metabolism;Neurons/cytology/*metabolism;Cells, Cultured;Olfactory Bulb/cytology/metabolism;Ciliary Neurotrophic Factor/metabolism/pharmacology;Receptors, Cytokine/deficiency/genetics;Cell Count;Animal;C abstr;Antigens, CD/metabolism;Prosencephalon/cytology/*metabolism;Injections, Intraventricular;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;Tyrosine 3-Monooxygenase/biosynthesis;Cell Lineage;Mice, Knockout;Macromolecular Systems;04 Adult neurogenesis factors;Stem Cells/cytology/drug effects/*metabolism;Membrane Glycoproteins/metabolism;Mice;Signal Transduction/physiology;Neuroglia/cytology/metabolism}, Number = {19}, Organization = {Genes &Development Research Group, Department of Cell Biology and Anatomy, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1.}, Pages = {7642-53.}, Title = {The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells}, Uuid = {4B11047F-8810-448B-B29C-AE8BCB1DE87A}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11567054%20http://www.jneurosci.org/cgi/content/full/21/19/7642%20http://www.jneurosci.org/cgi/content/abstract/21/19/7642}} @article{Shin:2004, Abstract = {How to minimize brain inflammation is pathophysiologically important, since inflammation induced by microglial activation can exacerbate brain damage. In the present report, we show that injection of lipopolysaccharide (LPS) into the rat cortex led to increased levels of interleukin-13 (IL-13) and to IL-13 immunoreactivity, followed by the substantial loss of microglia at 3 days post-LPS. IL-13 levels in LPS-injected cortex reached a peak at 12 h post-injection, remained elevated at 24 h, and returned to basal levels at day 4. In parallel, IL-13 immunoreactivity was detected as early as 12 h post-LPS and maintained up to 24 h; it disappeared at 4 days. Surprisingly, IL-13 immunoreactivity was detected exclusively in microglia, but not in neurons or astrocytes. Following treatment with LPS in vitro, IL-13 expression was also induced in microglia in the presence of neurons, but not in the presence of astrocytes or in cultured pure microglia alone. In experiments designed to determine the involvement of IL-13 in microglia cell death, IL-13-neutralizing antibodies significantly increased survival of activated microglia at 3 days post-LPS. Consistent with these results, the expression of inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-alpha) was sustained in activated microglia and neuronal cell death was consequently increased. Taken together, the present study is the first to demonstrate the endogenous expression of IL-13 in LPS-activated microglia in vivo, and to demonstrate that neurons may be required for IL-13 expression in microglia. Our data strongly suggest that IL-13 may control brain inflammation by inducing the death of activated microglia in vivo, resulting in an enhancement of neuronal survival.}, Author = {Shin, Won Ho and Lee, Da-Yong Y. and Park, Keun Woo and Kim, Seung Up and Yang, Myung-Soon S. and Joe, Eun-Hye H. and Jin, Byung Kwan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Cell Survival;Tumor Necrosis Factor;Animals;Cells, Cultured;Rats;Apoptosis;Female;Cell Communication;Rats, Sprague-Dawley;Microglia;Nitric-Oxide Synthase;Not relevant;11 Glia;Lipopolysaccharides;Alpha;Antibodies;Support, Non-U.S. Gov't;Interleukin-13;Cerebral Cortex;Neurons;Gene Expression}, Month = {4}, Nlm_Id = {8806785}, Number = {2}, Organization = {Brain Disease Research Center, Ajou University School of Medicine, Suwon, Korea.}, Pages = {142-52}, Pubmed = {15042582}, Title = {Microglia expressing interleukin-13 undergo cell death and contribute to neuronal survival in vivo}, Uuid = {8CFF8DC3-8555-4047-9CC4-313191388D26}, Volume = {46}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10357}} @article{Shin:2000, Abstract = {Reconstruction of complex neocortical and other CNS circuitry may be possible via transplantation of appropriate neural precursors, guided by cellular and molecular controls. Although cellular repopulation and complex circuitry repair may make possible new avenues of treatment for degenerative, developmental, or acquired CNS diseases, functional integration may depend critically on specificity of neuronal synaptic integration and appropriate neurotransmitter/receptor phenotype. The current study investigated neurotransmitter and receptor phenotypes of newly incorporated neurons after transplantation in regions of targeted neuronal degeneration of cortical callosal projection neurons (CPNs). Donor neuroblasts were compared to the population of normal endogenous CPNs in their expression of appropriate neurotransmitters (glutamate, aspartate, and GABA) and receptors (kainate-R, AMPA-R, NMDA-R. and GABA-R), and the time course over which this phenotype developed after transplantation. Transplanted immature neuroblasts from embryonic day 17 (E17) primary somatosensory (S1) cortex migrated to cortical layers undergoing degeneration, differentiated to a mature CPN phenotype, and received synaptic input from other neurons. In addition, 23.1 +/- 13.6\%of the donor-derived neurons extended appropriate long-distance callosal projections to the contralateral S1 cortex. The percentage of donor-derived neurons expressing appropriate neurotransmitters and receptors showed a steady increase with time, reaching numbers equivalent to adult endogenous CPNs by 4-16 weeks after transplantation. These results suggest that previously demonstrated changes in gene expression induced by synchronous apoptotic degeneration of adult CPNs create a cellular and molecular environment that is both permissive and instructive for the specific and appropriate maturation of transplanted neuroblasts. These experiments demonstrate, for the first time, that newly repopulating neurons can undergo directed differentiation with high fidelity of their neurotransmitter and receptor phenotype, toward reconstruction of complex CNS circuitry.}, Author = {Shin, J. J. and Fricker-Gates, R. A. and Perez, F. A. and Leavitt, B. R. and Zurakowski, D. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Survival;Lasers;Cell Differentiation;Animals;Stem Cell Transplantation;Synapses;Microinjections;Receptors, Cell Surface;Phenotype;Neocortex;Female;Cell Movement;Mice, Inbred C57BL;Male;Microspheres;Research Support, U.S. Gov't, P.H.S.;Neurons;Neurotransmitters;Porphyrins;Mice;24 Pubmed search results 2008;Stem Cells;Graft Survival;Corpus Callosum;Research Support, Non-U.S. Gov't}, Medline = {20482310}, Month = {10}, Nlm_Id = {8102140}, Number = {19}, Organization = {Division of Neuroscience, Children's Hospital, Department of Neurology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {7404-16}, Pubmed = {11007899}, Title = {Transplanted neuroblasts differentiate appropriately into projection neurons with correct neurotransmitter and receptor phenotype in neocortex undergoing targeted projection neuron degeneration}, Uuid = {5ADF41D1-FD71-408C-B448-8671E5994261}, Volume = {20}, Year = {2000}} @article{Shingo:2001, Abstract = {Recent studies have shown that neurogenesis is enhanced after hypoxia and that erythropoietin (EPO), an inducible cytokine, is produced in the brain as part of the intrinsic hypoxia response. Thus, we asked whether EPO might regulate neurogenesis by forebrain neural stem cells (NSCs). We found that EPO receptors are expressed in the embryonic germinal zone during neurogenesis as well as in the adult subventricular zone, which continues to generate neurons throughout adulthood. Cultured NSCs exposed to a modest hypoxia produced two- to threefold more neurons, which was associated with an elevation in EPO gene expression. The enhanced neuron production attributable to hypoxia was mimicked by EPO and blocked by coadministration of an EPO neutralizing antibody. EPO appears to act directly on NSCs, promoting the production of neuronal progenitors at the expense of multipotent progenitors. EPO infusion into the adult lateral ventricles resulted in a decrease in the numbers of NSCs in the subventricular zone, an increase in newly generated cells migrating to the olfactory bulb, and an increase in new olfactory bulb interneurons. Infusion of anti-EPO antibodies had the opposite effect: an increase in the number of NSCs in the subventricular zone and a decrease in the number of newly generated cells migrating to the bulb. These findings suggest that EPO is an autocrine-paracrine factor, capable of regulating the production of neuronal progenitor cells by forebrain NSCs.}, Author = {Shingo, T. and Sorokan, S. T. and Shimazaki, T. and Weiss, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurosci}, Keywords = {Olfactory Bulb/cytology/drug effects;Paracrine Communication/physiology;Cells, Cultured;NF-kappa B/antagonists &inhibitors/metabolism;Transcription Factors/biosynthesis;Cell Hypoxia/physiology;Interneurons/cytology/drug effects;Cell Movement/drug effects;Animal;Cell Count;Peptides/pharmacology;Cell Division/drug effects/physiology;C abstr;Injections, Intraventricular;Epidermal Growth Factor/pharmacology;Active Transport, Cell Nucleus/drug effects;Erythropoietin/antagonists &inhibitors/*metabolism/pharmacology;Support, Non-U.S. Gov't;Neurons/cytology/drug effects/*metabolism;Antibodies/administration &dosage/pharmacology;04 Adult neurogenesis factors;Stem Cells/cytology/drug effects/*metabolism;DNA-Binding Proteins/biosynthesis;Spheroids/cytology/drug effects;Mice;Lateral Ventricles/cytology/drug effects/physiology;Autocrine Communication/physiology;Prosencephalon/cytology/embryology/*metabolism}, Number = {24}, Organization = {Genes &Development Research Group, Department of Cell Biology and Anatomy, University of Calgary, Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1.}, Pages = {9733-43.}, Title = {Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells}, Uuid = {260F91B6-358D-4281-8311-A7F8F1E223C1}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11739582%20http://www.jneurosci.org/cgi/content/full/21/24/9733%20http://www.jneurosci.org/cgi/content/abstract/21/24/9733}} @article{Shingo:2003, Abstract = {Neurogenesis occurs in the olfactory system of the adult brain throughout life, in both invertebrates and vertebrates, but its physiological regulation is not understood. We show that the production of neuronal progenitors is stimulated in the forebrain subventricular zone of female mice during pregnancy and that this effect is mediated by the hormone prolactin. The progenitors then migrate to produce new olfactory interneurons, a process likely to be important for maternal behavior, because olfactory discrimination is critical for recognition and rearing of offspring. Neurogenesis occurs even in females that mate with sterile males. These findings imply that forebrain olfactory neurogenesis may contribute to adaptive behaviors in mating and pregnancy. 1095-9203 Journal Article}, Author = {Shingo, T. and Gregg, C. and Enwere, E. and Fujikawa, H. and Hassam, R. and Geary, C. and Cross, J. C. and Weiss, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Science}, Keywords = {Pregnancy;Cell Differentiation;Signal Transduction;Choroid Plexus/metabolism;Olfactory Bulb/*cytology;Animals;Cells, Cultured;Neurons/cytology/*physiology;Pseudopregnancy;Estradiol/administration &dosage/pharmacology;Female;Cell Movement;Dentate Gyrus/cytology;Progesterone/administration &dosage/pharmacology;Stem Cells/*cytology;Male;Epidermal Growth Factor/pharmacology;Prosencephalon/*cytology/*physiology;Support, Non-U.S. Gov't;C;Interneurons/cytology/*physiology;Prolactin/administration &dosage/blood/pharmacology/*physiology;04 Adult neurogenesis factors;Receptors, Prolactin/genetics/metabolism;Cell Division;Mice}, Number = {5603}, Organization = {Genes &Development Research Group, Department of Cell Biology and Anatomy, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada T2N 4N1.}, Pages = {117-20}, Pubmed = {12511652}, Title = {Pregnancy-stimulated neurogenesis in the adult female forebrain mediated by prolactin}, Uuid = {F096B588-6F39-48AC-A5AF-E4FE8C37E5A3}, Volume = {299}, Year = {2003}, url = {papers/Shingo_Science2003.pdf}} @article{Shlens:2006, Abstract = {Current understanding of many neural circuits is limited by our ability to explore the vast number of potential interactions between different cells. We present a new approach that dramatically reduces the complexity of this problem. Large-scale multi-electrode recordings were used to measure electrical activity in nearly complete, regularly spaced mosaics of several hundred ON and OFF parasol retinal ganglion cells in macaque monkey retina. Parasol cells exhibited substantial pairwise correlations, as has been observed in other species, indicating functional connectivity. However, pairwise measurements alone are insufficient to determine the prevalence of multi-neuron firing patterns, which would be predicted from widely diverging common inputs and have been hypothesized to convey distinct visual messages to the brain. The number of possible multi-neuron firing patterns is far too large to study exhaustively, but this problem may be circumvented if two simple rules of connectivity can be established: (1) multi-cell firing patterns arise from multiple pairwise interactions, and (2) interactions are limited to adjacent cells in the mosaic. Using maximum entropy methods from statistical mechanics, we show that pairwise and adjacent interactions accurately accounted for the structure and prevalence of multi-neuron firing patterns, explaining approximately 98\%of the departures from statistical independence in parasol cells and approximately 99\%of the departures that were reproducible in repeated measurements. This approach provides a way to define limits on the complexity of network interactions and thus may be relevant for probing the function of many neural circuits.}, Author = {Shlens, Jonathon and Field, Greg D. and Gauthier, Jeffrey L. and Grivich, Matthew I. and Petrusca, Dumitru and Sher, Alexander and Litke, Alan M. and Chichilnisky, E. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Photic Stimulation;research support, non-u.s. gov't;Visual Perception;Macaca mulatta;Action Potentials;Models, Neurological;Computer Simulation;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;Retinal Ganglion Cells;Nerve Net;Animals;Cells, Cultured;Synaptic Transmission;Visual Fields;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {32}, Organization = {Department of Systems Neurobiology, The Salk Institute, La Jolla, California 92037, USA. shlens\@salk.edu}, Pages = {8254-66}, Pii = {26/32/8254}, Pubmed = {16899720}, Title = {The structure of multi-neuron firing patterns in primate retina}, Uuid = {09F69EA2-FC4C-47FE-AAD2-C01AA38B5414}, Volume = {26}, Year = {2006}, url = {papers/Shlens_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1282-06.2006}} @article{Shojaei:2005, Abstract = {The molecular basis governing functional behavior of human hematopoietic stem cells (HSCs) is largely unknown. Here, using in vitro and in vivo assays, we isolate and define progenitors versus repopulating HSCs from multiple stages of human development for global gene expression profiling. Accounting for both the hierarchical relationship between repopulating cells and their progenitors, and the enhanced HSC function unique to early stages of ontogeny, the human homologs of Hairy Enhancer of Split-1 (HES-1) and Hepatocyte Leukemia Factor (HLF) were identified as candidate regulators of HSCs. Transgenic human hematopoietic cells expressing HES-1 or HLF demonstrated enhanced in vivo reconstitution ability that correlated to increased cycling frequency and inhibition of apoptosis, respectively. Our report identifies regulatory factors involved in HSC function that elicit their effect through independent systems, suggesting that a unique orchestration of pathways fundamental to all human cells is capable of controlling stem cell behavior.}, Author = {Shojaei, Farbod and Trowbridge, Jennifer and Gallacher, Lisa and Yuefei, Lou and Goodale, David and Karanu, Francis and Levac, Krysta and Bhatia, Mickie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1534-5807}, Journal = {Dev Cell}, Keywords = {22 Stem cells;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {101120028}, Number = {5}, Organization = {Stem Cell Biology and Regenerative Medicine, Robarts Research Institute, London, Ontario, Canada.}, Pages = {651-63}, Pii = {S1534-5807(05)00088-2}, Pubmed = {15866157}, Title = {Hierarchical and ontogenic positions serve to define the molecular basis of human hematopoietic stem cell behavior}, Uuid = {67E6BBB7-D2F7-4159-89E5-0CD153FE8557}, Volume = {8}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.devcel.2005.03.004}} @article{Shors:2001, Abstract = {The vertebrate brain continues to produce new neurons throughout life. In the rat hippocampus, several thousand are produced each day, many of which die within weeks. Associative learning can enhance their survival; however, until now it was unknown whether new neurons are involved in memory formation. Here we show that a substantial reduction in the number of newly generated neurons in the adult rat impairs hippocampal-dependent trace conditioning, a task in which an animal must associate stimuli that are separated in time. A similar reduction did not affect learning when the same stimuli are not separated in time, a task that is hippocampal-independent. The reduction in neurogenesis did not induce death of mature hippocampal neurons or permanently alter neurophysiological properties of the CA1 region, such as long-term potentiation. Moreover, recovery of cell production was associated with the ability to acquire trace memories. These results indicate that newly generated neurons in the adult are not only affected by the formation of a hippocampal-dependent memory, but also participate in it.}, Author = {Shors, T. J. and Miesegaes, G. and Beylin, A. and Zhao, M. and Rydel, T. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Nature}, Keywords = {A-12}, Number = {6826}, Organization = {Department of Psychology and Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854, USA.}, Pages = {372-6.}, Title = {Neurogenesis in the adult is involved in the formation of trace memories}, Uuid = {A4A47235-CDEF-11D9-B244-000D9346EC2A}, Volume = {410}, Year = {2001}, url = {papers/Shors_Nature2001.pdf}} @article{Shrikant:1996, Abstract = {It is well established that the two major glial cells in the central nervous system (CNS), astrocytes and microglia, are key participants in mediating the neurologic dysfunction associated with HIV infection of the CNS. In this study, we investigated the ability of the major envelope glycoprotein of HIV, glycoprotein 120 (gp120), to regulate intercellular adhesion molecule-1 (ICAM-1) expression in glial cells, because ICAM-1 is important in mediating immune responsiveness in the CNS, facilitating entry of HIV-infected cells into the CNS, and promoting syncytia formation. Our results indicate that gp120 enhances ICAM-1 gene expression in primary rat astrocytes, primary human astrocytes, a human astroglioma cell line CRT, and primary rat microglia. The signal transduction events involved in gp120-mediated enhancement of ICAM-1 appear to involve activation of both protein kinase C and tyrosine kinase, because inhibitors of protein kinase C and tyrosine kinase abrogate gp120-mediated ICAM-1 expression in both astrocytes and microglia. Moreover, gp120 induces tyrosine phosphorylation of signal transducer and activator of transcription (STAT-1 alpha) as well as the Janus kinase (JAK2) in glial cells. We also demonstrate that gp120-mediated ICAM-1 expression has functional significance, as it enhances the ability of monocytic cells to bind to gp120-stimulated human astrocytes in an ICAM-1/beta 2 integrin-dependent fashion. These results provide new insights into how gp120 can influence the involvement of glial cells in the pathogenesis of AIDS dementia complex.}, Author = {Shrikant, P. and Benos, D. J. and Tang, L. P. and Benveniste, E. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {Antigens, CD18;Human;Signal Transduction;Protein Kinase C;HIV-1;DNA-Binding Proteins;Intercellular Adhesion Molecule-1;Trans-Activators;Monocytes;Rats;Astrocytes;Animals;Microglia;viral;Phosphorylation;Humans;Macrophage Activation;11 Glia;RNA, Messenger;Cell Line;Research Support, U.S. Gov't, P.H.S.;Cell Adhesion;Tumor Cells, Cultured;Astrocytoma;Neuroglia;Support, U.S. Gov't, P.H.S.;Proto-Oncogene Proteins;Protein-Tyrosine Kinase;HIV Envelope Protein gp120}, Medline = {96144358}, Month = {2}, Nlm_Id = {2985117R}, Number = {3}, Organization = {Department of Cell Biology, University of Alabama, Birmingham 35294, USA.}, Pages = {1307-14}, Pubmed = {8558011}, Title = {HIV glycoprotein 120 enhances intercellular adhesion molecule-1 gene expression in glial cells. Involvement of Janus kinase/signal transducer and activator of transcription and protein kinase C signaling pathways}, Uuid = {B52CBE71-9253-45C9-BE67-D0565F5FA0E5}, Volume = {156}, Year = {1996}} @article{Shu:2001, Abstract = {Glutamate is the main neurotransmitter in the olfactory bulb. Recently, postsynaptic-density 95 (PSD-95) and neuronal activity-regulated pentraxin (Narp) have been reported to be pivotal for targeting and clustering of NMDA receptors and AMPA receptors, respectively. We thus investigated the expressions of PSD-95 and Narp mRNAs in the rat developing olfactory bulb. PSD-95 mRNA was already expressed in most neurons on the first postnatal day (P1). On the other hand, Narp mRNA expression was weakly seen only in mitral cells on P1. Thereafter, we found initial expression of Narp mRNA on P7 in periglomerular cells, and on P14 in granular cells, indicating that in the developing olfactory bulb PSD-95 mRNA expression precedes Narp mRNA expression, and that the expression pattern of Narp mRNA seems to be well correlated with the maturation of the neurons. These results indicate that PSD-95 and Narp play important roles in making efficient excitatory synapses in the developing rat olfactory bulb, and suggest that olfactory neurons might first express PSD-95 for making efficient NMDA receptors and thereafter express Narp for efficient AMPA receptors.}, Author = {Shu, F. and Ohno, K. and Wang, T. and Kuriyama, K. and Ueki, T. and Kanayama, N. and Sato, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {13 Olfactory bulb anatomy;I both}, Number = {1}, Organization = {Department of Anatomy and Neuroscience, Hamamatsu University School of Medicine, 1-20-1 Handa Yama, Hamamatsu, 431-3192, Shizuoka, Japan}, Pages = {91-5.}, Title = {Developmental changes in PSD-95 and Narp mRNAs in the rat olfactory bulb}, Uuid = {67A29101-32C6-46C7-9D3A-4B3A093CAA5B}, Volume = {132}, Year = {2001}, url = {papers/Shu_BrainResDevBrainRes2001}} @article{Shu:2006, Abstract = {The mechanisms controlling neurogenesis during brain development remain relatively unknown. Through a differential protein screen with developmental versus mature neural tissues, we identified a group of developmentally enriched microtubule-associated proteins (MAPs) including doublecortin-like kinase (DCLK), a protein that shares high homology with doublecortin (DCX). DCLK, but not DCX, is highly expressed in regions of active neurogenesis in the neocortex and cerebellum. Through a dynein-dependent mechanism, DCLK regulates the formation of bipolar mitotic spindles and the proper transition from prometaphase to metaphase during mitosis. In cultured cortical neural progenitors, DCLK RNAi Lentivirus disrupts the structure of mitotic spindles and the progression of M phase, causing an increase of cell-cycle exit index and an ectopic commitment to a neuronal fate. Furthermore, both DCLK gain and loss of function in vivo specifically promote a neuronal identity in neural progenitors. These data provide evidence that DCLK controls mitotic division by regulating spindle formation and also determines the fate of neural progenitors during cortical neurogenesis.}, Author = {Shu, Tianzhi and Tseng, Huang-Chun C. and Sapir, Tamar and Stern, Patrick and Zhou, Ying and Sanada, Kamon and Fischer, Andre and Coquelle, Fr{\'e}d{\'e}ric M. and Reiner, Orly and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Cell Differentiation;research support, n.i.h., extramural ;Animals;Cells, Cultured;Humans;Microtubule-Associated Proteins;Mitosis;Nervous System;Mitotic Spindle Apparatus;Embryonic Development;Protein-Serine-Threonine Kinases;research support, non-u.s. gov't;Prometaphase;research support, non-u.s. gov't ;Microtubules;Cerebral Cortex;Neurons;research support, n.i.h., extramural;Mice;Dynein ATPase;24 Pubmed search results 2008;Cell Division;Stem Cells}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {25-39}, Pii = {S0896-6273(05)01007-X}, Pubmed = {16387637}, Title = {Doublecortin-like kinase controls neurogenesis by regulating mitotic spindles and M phase progression}, Uuid = {AD94642C-A1E0-42DA-B940-559D38F46450}, Volume = {49}, Year = {2006}, url = {papers/Shu_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.10.039}} @article{Shuaib:1994, Abstract = {Hypothyroidism protects the brain from the effects of transient forebrain ischemia in gerbils. The mechanism for this protection is not fully understood. In this study we looked at the release of glutamate during ischemia in gerbils exposed to surgical hypothyroidism (n = 7), chemical hypothyroidism (n = 8), and surgical hypothyroidism thyroxine-treated (n = 3) and compared them to control euthyroid animals (n = 8). The duration of ischemia was 10 min. Glutamate release was measured with in vivo microdialysis. Microdialysis analysis began 2 h after the placement of the probes (to stabilize the baseline) and collections were obtained in 10-min samples. During ischemia, there was an increase in the release of glutamate that returned to the baseline within 20 min following the insult. In animals made hypothyroid surgically and chemically, the extent of glutamate release was significantly lower than that in the controls. The release of glutamate in the surgically hypothyroid thyroxine-treated animals was similar to that in controls. The attenuated glutamate release could be a mechanism of protection during ischemia in hypothyroid gerbils. 0014-4886 Journal Article}, Author = {Shuaib, A. and Ijaz, S. and Hemmings, S. and Galazka, P. and Ishaqzay, R. and Liu, L. and Ravindran, J. and Miyashita, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Exp Neurol}, Keywords = {Male;Propylthiouracil;Thyroidectomy;Brain Ischemia/*metabolism;Triiodothyronine/blood;06 Adult neurogenesis injury induced;Microdialysis;Glutamates/*metabolism;Gerbillinae;D pdf;Animals;Support, Non-U.S. Gov't;Thyroxine/blood/pharmacology;Hypothyroidism/chemically induced/etiology/*metabolism;Glutamic Acid}, Number = {2}, Organization = {Department of Medicine (Neurology), Saskatchewan Stroke Research Centre, Saskatoon, Canada.}, Pages = {260-5}, Pubmed = {7915676}, Title = {Decreased glutamate release during hypothyroidism may contribute to protection in cerebral ischemia}, Uuid = {444C4195-79C0-4CB7-B6B8-639C7EAF917E}, Volume = {128}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7915676}} @article{Shuaib:1994a, Abstract = {The mechanisms by which brain cells die after brief episodes of cerebral ischemia are not fully understood. In certain brain regions this damage may not be apparent for days. Hypothyroidism is known to decrease cerebral metabolism. We postulated that this slowing in cerebral metabolism may be neuroprotective after transient cerebral ischemia. To test this hypothesis, a total of 10 gerbils had thyroidectomies performed 2 weeks prior to ischemia. Six gerbils served as euthyroid controls. All animals were exposed to 5 min of transient ischemia and sacrificed 7 days after the insult. Silver degeneration staining was used for histological evaluation. Hippocampal damage [subiculum (P <0.001), CA1 (P = 0. <.001), CA3 (P <0.05), and CA4 (P <0.001)] was significantly less in the hypothyroid animals. There was also significantly less damage in the cerebral cortex (P <0.05) and thalamus (P <0.05) in the hypothyroid animals. The exact mechanism of this protection is not fully understood but could be secondary to a decrease in the metabolic activity, or a reduced generation of free radicals (as is seen with protection from ischemia in kidney and liver under hypothyroid conditions). Further studies are required in order to gain a better understanding of the protective effects of hypothyroidism on cerebral ischemia. 0014-4886 Journal Article}, Author = {Shuaib, A. and Ijaz, S. and Mazagri, R. and Kalra, J. and Hemmings, S. and Senthilsvlvan, A. and Crosby, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Exp Neurol}, Keywords = {control;Insulin/blood;Animals;Triiodothyronine/blood;Ischemic Attack, Transient/*pathology/physiopathology/*prevention &;Gerbillinae;Brain/*pathology;Pyramidal Cells/pathology;Hippocampus/pathology;D pdf;gamma-Glutamyltransferase/blood/metabolism;Hypothyroidism/blood/pathology/*physiopathology;Reference Values;Ketone Bodies/blood;Male;Time Factors;Liver/enzymology;Support, Non-U.S. Gov't;Blood Glucose/metabolism;Thyroidectomy;06 Adult neurogenesis injury induced;Thyroxine/blood;Cerebral Cortex/pathology;Thalamus/pathology}, Number = {1}, Organization = {Department of Medicine (Neurology), College of Medicine, University of Saskatchewan, Canada.}, Pages = {119-25}, Pubmed = {7911086}, Title = {Hypothyroidism protects the brain during transient forebrain ischemia in gerbils}, Uuid = {6BF481B6-8019-4071-BFEF-3B9BE40B494B}, Volume = {127}, Year = {1994}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7911086}} @article{Shumate:1998, Abstract = {Using patch clamp recording techniques in dentate granule cells (DGCs) isolated from patients undergoing temporal lobectomy for intractable epilepsy, we investigated basic properties of GABA(A) receptors (GABA(A)Rs) and pharmacological sensitivity of GABA-evoked currents to modulation by zinc and benzodiazepines (BZ). Properties of human DGC GABA(A)Rs were compared to DGC GABA(A)R properties in control and epileptic rats. Blockade of GABA evoked currents by zinc was significantly enhanced in epileptic human relative to control rat DGCs. Augmentation of the GABA(A)R current by the non-subunit selective BZ agonist, clonazepam (CNZ) and by the BZ1 specific agonist, zolpidem (ZOL), were not significantly different in human DGCs relative to control or epileptic rat. GABA potency was significantly higher in epileptic human DGCs than in control or epileptic rat DGCs. The significantly enhanced efficacy of zinc in blocking GABA currents in epileptic human DGCs mirrors that seen in epileptic rat DGCs, and was coupled with mossy fiber sprouting evident in both epileptic human and rat dentate gyrus. The aberrant mossy fibers provide a novel zinc delivery system within the epileptic dentate gyrus. The mossy fiber release of zinc onto DGCs coupled with the enhanced zinc sensitivity of GABA(A)Rs in epileptic DGCs, may lead to 'dynamic disinhibition' which could compromise inhibitory efficacy in the epileptic rat and human hippocampus.}, Author = {Shumate, M. D. and Lin, D. D. and Gibbs, J. W. and Holloway, K. L. and Coulter, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {GABA Agonists;gamma-Aminobutyric Acid;Pilocarpine;Animals;N-Methylscopolamine;Humans;Rats;Comparative Study;21 Epilepsy;Rats, Sprague-Dawley;Male;Status Epilepticus;Research Support, U.S. Gov't, P.H.S.;Receptors, GABA-A;Epilepsy, Temporal Lobe;Neurons;21 Neurophysiology;Zinc;Dentate Gyrus;GABA Antagonists;Temporal Lobe;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {98432481}, Month = {9}, Nlm_Id = {8703089}, Number = {1-2}, Organization = {Department of Physiology, Medical College of Virginia, Richmond 23398-0599, USA.}, Pages = {114-28}, Pubmed = {9761314}, Title = {GABA(A) receptor function in epileptic human dentate granule cells: comparison to epileptic and control rat}, Uuid = {CDAA75A5-D1D1-4017-BDBA-F62DF7117241}, Volume = {32}, Year = {1998}} @article{Shykind:2004, Abstract = {Individual olfactory sensory neurons express only a single odorant receptor from a large family of genes, and this singularity is an essential feature in models of olfactory perception. We have devised a genetic strategy to examine the stability of receptor choice. We observe that immature olfactory sensory neurons that express a given odorant receptor can switch receptor expression, albeit at low frequency. Neurons that express a mutant receptor gene switch receptor transcription with significantly greater probability, suggesting that the expression of a functional odorant receptor elicits a feedback signal that terminates switching. This process of receptor gene switching assures that a neuron will ultimately express a functional receptor and that the choice of this receptor will remain stable for the life of the cell.}, Author = {Shykind, Benjamin M. and Rohani, S. Christy and O'Donnell, Sean and Nemes, Adriana and Mendelsohn, Monica and Sun, Yonghua and Axel, Richard and Barnea, Gilad}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:58 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Trans-Activation (Genetics);13 Olfactory bulb anatomy;Cell Differentiation;Feedback, Biochemical;Animals;Synapses;Gene Expression Regulation, Developmental;Olfactory Receptor Neurons;Apoptosis;Mutation;Integrases;Mice, Inbred C57BL;RNA, Messenger;Olfactory Bulb;Smell;Support, Non-U.S. Gov't;Cell Lineage;Support, U.S. Gov't, P.H.S.;Receptors, Odorant;Mice;Luminescent Proteins;Growth Cones;Genes, Reporter;Viral Proteins}, Month = {6}, Nlm_Id = {0413066}, Number = {6}, Organization = {Department of Biochemistry and Molecular Biophysics and Howard Hughes Medical Institute, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.}, Pages = {801-15}, Pii = {S009286740400529X}, Pubmed = {15186780}, Title = {Gene switching and the stability of odorant receptor gene choice}, Uuid = {8CC6AF22-62B9-456E-874F-1D16B483682B}, Volume = {117}, Year = {2004}, url = {papers/Shykind_Cell2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2004.05.015}} @article{Si:2003, Abstract = {Synapse-specific facilitation requires rapamycin-dependent local protein synthesis at the activated synapse. In Aplysia, rapamycin-dependent local protein synthesis serves two functions: (1) it provides a component of the mark at the activated synapse and thereby confers synapse specificity and (2) it stabilizes the synaptic growth associated with long-term facilitation. Here we report that a neuron-specific isoform of cytoplasmic polyadenylation element binding protein (CPEB) regulates this synaptic protein synthesis in an activity-dependent manner. Aplysia CPEB protein is upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long-term facilitation. We suggest that Aplysia CPEB is one of the stabilizing components of the synaptic mark. 0092-8674 Journal Article}, Author = {Si, K. and Giustetto, M. and Etkin, A. and Hsu, R. and Janisiewicz, A. M. and Miniaci, M. C. and Kim, J. H. and Zhu, H. and Kandel, E. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Cell}, Keywords = {10 Development;F pdf}, Number = {7}, Organization = {Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USA. ks560\@columbia.edu}, Pages = {893-904}, Pubmed = {14697206}, Title = {A neuronal isoform of CPEB regulates local protein synthesis and stabilizes synapse-specific long-term facilitation in aplysia}, Uuid = {364054C6-97A5-4275-8596-AC37647E9495}, Volume = {115}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14697206}} @article{Si:2003a, Abstract = {Prion proteins have the unusual capacity to fold into two functionally distinct conformations, one of which is self-perpetuating. When yeast prion proteins switch state, they produce heritable phenotypes. We report prion-like properties in a neuronal member of the CPEB family (cytoplasmic polyadenylation element binding protein), which regulates mRNA translation. Compared to other CPEB family members, the neuronal protein has an N-terminal extension that shares characteristics of yeast prion-determinants: a high glutamine content and predicted conformational flexibility. When fused to a reporter protein in yeast, this region confers upon it the epigenetic changes in state that characterize yeast prions. Full-length CPEB undergoes similar changes, but surprisingly it is the dominant, self-perpetuating prion-like form that has the greatest capacity to stimulate translation of CPEB-regulated mRNA. We hypothesize that conversion of CPEB to a prion-like state in stimulated synapses helps to maintain long-term synaptic changes associated with memory storage. 0092-8674 Journal Article}, Author = {Si, K. and Lindquist, S. and Kandel, E. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Cell}, Keywords = {10 Development;F pdf}, Number = {7}, Organization = {Center for Neurobiology and Behavior, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 722 West 168th Street, New York, NY 10032, USA. ks560\@columbia.edu}, Pages = {879-91}, Pubmed = {14697205}, Title = {A neuronal isoform of the aplysia CPEB has prion-like properties}, Uuid = {74754E0D-2FC2-40E2-85C8-532AE54B1588}, Volume = {115}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14697205}} @article{Si:2002, Abstract = {Significant numbers of patients with acquired immunodeficiency syndrome (AIDS) develop CNS infection primarily in macrophages and microglial cells. Therefore, the regulation of human immunodeficiency virus type 1 (HIV-1) infection and activation of the brain mononuclear phagocytes subsequent to infection are important areas of investigation. In the current report, we studied the role of granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage-CSF (M-CSF) in the expression of antiviral beta-chemokines and HIV-1 p24 in cultures of primary human fetal microglia. We found that stimulation with GM-CSF or M-CSF induced macrophage inflammatory proteins (MIP-1alpha and MIP-1beta) and augmented RANTES expression, after HIV-1 infection of microglia. This was not due to the effect of GM-CSF on viral expression because GM-CSF was neither necessary nor stimulatory for viral infection, nor did GM-CSF enhance the expression of env-pseudotyped reporter viruses. Blocking GM-CSF-induced microglial proliferation by nocodazole had no effect on beta-chemokine or p24 expression. The functional significance of the GM-CSF-induced beta-chemokines was suggested by the finding that, in the presence of GM-CSF, exogenous beta-chemokines lost their anti-HIV-1 effects. We further show that although HIV-1-infected microglia produced M-CSF, they failed to produce GM-CSF. In vivo, GM-CSF expression was localized to activated astrocytes and some inflammatory cells in HIV-1 encephalitis, suggesting paracrine activation of microglia through GM-CSF. Our results demonstrate a complex interplay between CSFs, chemokines, and virus in microglial cells and may have bearing on the interpretation of data derived in vivo and in vitro.}, Author = {Si, Qiusheng and Cosenza, Melissa and Zhao, Meng-Liang L. and Goldstein, Harris and Lee, Sunhee C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Fetus;Dose-Response Relationship, Drug;Pregnancy;HIV-1;Humans;Cells, Cultured;Adjuvants, Immunologic;Brain;Microglia;Female;Macrophage Activation;Recombinant Fusion Proteins;Granulocyte-Macrophage Colony-Stimulating Factor;11 Glia;Chemokines, CC;Research Support, U.S. Gov't, P.H.S.;RANTES;Heat;Macrophage Colony-Stimulating Factor;Macrophage Inflammatory Protein-1;HIV Core Protein p24;Virus Replication;Cell Division;AIDS Dementia Complex}, Medline = {22106033}, Month = {8}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.}, Pages = {174-83}, Pubmed = {12112368}, Title = {GM-CSF and M-CSF modulate beta-chemokine and HIV-1 expression in microglia}, Uuid = {4DDF3FDD-1CC9-4D3A-9141-DCFFB649C288}, Volume = {39}, Year = {2002}, url = {papers/Si_Glia2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10095}} @article{Siapas:2005, Abstract = {The interactions between cortical and hippocampal circuits are critical for memory formation, yet their basic organization at the neuronal network level is not well understood. Here, we demonstrate that a significant portion of neurons in the medial prefrontal cortex of freely behaving rats are phase locked to the hippocampal theta rhythm. In addition, we show that prefrontal neurons phase lock best to theta oscillations delayed by approximately 50 ms and confirm this hippocampo-prefrontal directionality and timing at the level of correlations between single cells. Finally, we find that phase locking of prefrontal cells is predicted by the presence of significant correlations with hippocampal cells at positive delays up to 150 ms. The theta-entrained activity across cortico-hippocampal circuits described here may be important for gating information flow and guiding the plastic changes that are believed to underlie the storage of information across these networks.}, Author = {Siapas, Athanassios G. and Lubenov, Evgueniy V. and Wilson, Matthew A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Theta Rhythm;21 Neurophysiology;Hippocampus;research support, non-u.s. gov't ;Neural Pathways;Prefrontal Cortex;Rats;Animals;comparative study ;Male;Neurons;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8809320}, Number = {1}, Organization = {Computation and Neural Systems Program, Division of Biology, California Institute of Technology, Pasadena, California 91125, USA. thanos\@caltech.edu}, Pages = {141-51}, Pii = {S0896-6273(05)00197-2}, Pubmed = {15820700}, Title = {Prefrontal phase locking to hippocampal theta oscillations}, Uuid = {83061507-AFF7-4187-8369-3A2036F82F48}, Volume = {46}, Year = {2005}, url = {papers/Siapas_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.02.028}} @article{Sieburth:2005, Abstract = {Chemical synapses are complex structures that mediate rapid intercellular signalling in the nervous system. Proteomic studies suggest that several hundred proteins will be found at synaptic specializations. Here we describe a systematic screen to identify genes required for the function or development of Caenorhabditis elegans neuromuscular junctions. A total of 185 genes were identified in an RNA interference screen for decreased acetylcholine secretion; 132 of these genes had not previously been implicated in synaptic transmission. Functional profiles for these genes were determined by comparing secretion defects observed after RNA interference under a variety of conditions. Hierarchical clustering identified groups of functionally related genes, including those involved in the synaptic vesicle cycle, neuropeptide signalling and responsiveness to phorbol esters. Twenty-four genes encoded proteins that were localized to presynaptic specializations. Loss-of-function mutations in 12 genes caused defects in presynaptic structure.}, Author = {Sieburth, Derek and Ch'ng, QueeLim and Dybbs, Michael and Tavazoie, Masoud and Kennedy, Scott and Wang, Duo and Dupuy, Denis and Rual, Jean-Fran\c{c}ois F. and Hill, David E. and Vidal, Marc and Ruvkun, Gary and Kaplan, Joshua M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Fluorescence;research support, n.i.h., extramural ;Animals;Phorbol Esters;Synapses;Microfilament Proteins;Caenorhabditis elegans;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Protein Transport;Mutation;Synaptic Vesicles;Cluster Analysis;RNA Interference;Gene Expression Profiling;Neuropeptides;research support, non-u.s. gov't ;Neuromuscular Junction;21 Neurophysiology;Cytoskeleton;Aldicarb;Caenorhabditis elegans Proteins;Motor Neurons;24 Pubmed search results 2008;Drug Resistance;Membrane Proteins;Nerve Tissue Proteins;R-SNARE Proteins}, Month = {7}, Nlm_Id = {0410462}, Number = {7050}, Organization = {Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.}, Pages = {510-7}, Pii = {nature03809}, Pubmed = {16049479}, Title = {Systematic analysis of genes required for synapse structure and function}, Uuid = {B9FEB382-FB29-4ACB-9B53-D0B469B377C7}, Volume = {436}, Year = {2005}, url = {papers/Sieburth_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03809}} @article{Sieczkarski:2003, Abstract = {Enveloped viruses often enter cells via endocytosis; however, specific endocytic trafficking pathway(s) for many viruses have not been determined. Here we demonstrate, through the use of dominant-negative Rab5 and Rab7, that influenza virus (Influenza A/WSN/33 (H1N1) and A/X-31 (H3N2)) requires both early and late endosomes for entry and subsequent infection in HeLa cells. Time-course experiments, monitoring viral ribonucleoprotein colocalization with endosomal markers, indicated that influenza exhibits a conventional endocytic uptake pattern--reaching early endosomes after approximately 10 min, and late endosomes after 40 min. Detection with conformation-specific hemagglutinin antibodies indicated that hemagglutinin did not reach a fusion-competent form until the virus had trafficked beyond early endosomes. We also examined two other enveloped viruses that are also pH-dependent for entry--Semliki Forest virus and vesicular stomatitis virus. In contrast to influenza virus, infection with both Semliki Forest virus and vesicular stomatitis virus was inhibited only by the expression of dominant negative Rab5 and not by dominant negative Rab7, indicating an independence of late endosome function for infection by these viruses. As a whole, these data provide a definitive characterization of influenza virus endocytic trafficking and show differential requirements for endocytic trafficking between pH-dependent enveloped viruses.}, Author = {Sieczkarski, Sara B. and Whittaker, Gary R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {1398-9219}, Journal = {Traffic}, Keywords = {Rhabdoviridae Infections;Semliki forest virus;Research Support, Non-U.S. Gov't;Hela Cells;Research Support, U.S. Gov't, P.H.S.;rab GTP-Binding Proteins;Endosomes;Orthomyxoviridae Infections;rab5 GTP-Binding Proteins;Vesicular stomatitis-Indiana virus;Endocytosis;Orthomyxoviridae;Humans;15 Retrovirus mechanism;24 Pubmed search results 2008;Alphavirus Infections}, Medline = {22601024}, Month = {5}, Nlm_Id = {100939340}, Number = {5}, Organization = {Department of Microbiology & Immunology, Cornell University, Ithaca, NY, USA.}, Pages = {333-43}, Pii = {090}, Pubmed = {12713661}, Title = {Differential requirements of Rab5 and Rab7 for endocytosis of influenza and other enveloped viruses}, Uuid = {8BE28386-C1C1-4517-A039-1D0643763B31}, Volume = {4}, Year = {2003}} @article{Sierra:2007, Abstract = {Microglia play a critical role in neurodegenerative diseases and in the brain aging process. Yet, little is known about the functional dynamics of microglia during aging. Thus, using young and aging transgenic mice expressing enhanced-green fluorescent protein (EGFP) under the promoter of the c-fms gene for macrophage-colony stimulating factor receptor, we evaluated invivo-induced inflammatory responses of EGFP-expressing microglia sorted by flow cytometry. Aging microglia were characterized by the presence of lipofuscin granules, decreased processes complexity, altered granularity, and increased mRNA expression of both pro-inflammatory (TNFalpha, IL-1beta, IL-6) and anti-inflammatory (IL-10, TGFbeta1) cytokines. Following lipopolysaccharide (LPS) challenge (1 mg/kg, 3 h), aging microglia exhibit increased basal expression of TNFalpha, IL-1beta, IL-6, and IL-10. Yet, the fold-over-basal LPS response remained constant across age, implying that the inflammatory machinery in aging microglia is functional and adjusted to the basal state. Gender differences were not overall observed across the treatments (age, LPS). The low but sustained production of pro-inflammatory cytokines by aging microglia may have a profound impact in the brain aging process. (c) 2007 Wiley-Liss, Inc.}, Author = {Sierra, and Gottfried-Blackmore, and McEwen, and Bulloch,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8806785}, Organization = {Laboratory of Neuroendocrinology, Rockefeller University, New York, New York.}, Pubmed = {17203473}, Title = {Microglia derived from aging mice exhibit an altered inflammatory profile}, Uuid = {52724559-8B15-4022-BBB5-89AC382C61F4}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20468}} @article{Sievers:2003, Abstract = {Wallerian degeneration, the disintegration of the distal part of an injured axon, is an important event in many neurodegenerative diseases. We studied Wallerian degeneration in dorsal root ganglion (DRG) explants in culture by separating neurites from their cell bodies with a scalpel. The severed neurites showed Annexin V positive staining, that spreads distally with a rate comparable to that of slow axonal transport in intact neurons in vivo. Moreover, the injured neurites showed loss of mitochondrial membrane potential. These features resemble those seen when cells undergo apoptosis. These data contribute to a new understanding of the mechanism of axonal degeneration, have implications for the response of stromal cells in central nervous system (CNS) and raise the prospect of new pharmacological treatments for those neurodegenerative pathologies where the protection of the cell body alone does not alleviate the disease.}, Author = {Sievers, Caroline and Platt, Nick and Perry, V. Hugh and Coleman, Michael P. and Conforti, Laura}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Cell Culture Techniques;Animals;Osmolar Concentration;Ganglia, Spinal;Enzyme Inhibitors;Comparative Study;Cycloheximide;Apoptosis;Mitochondria;Neurites;Protein Synthesis Inhibitors;Staurosporine;Wallerian Degeneration;Annexin A5;Axotomy;Membrane Potentials;Mice;24 Pubmed search results 2008;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {22653026}, Month = {6}, Nlm_Id = {8500749}, Number = {2}, Organization = {Center for Molecular Medicine (ZMMK) and Institute for Genetics, University of Cologne, Germany.}, Pages = {161-9}, Pii = {S0168010203000397}, Pubmed = {12767479}, Title = {Neurites undergoing Wallerian degeneration show an apoptotic-like process with Annexin V positive staining and loss of mitochondrial membrane potential}, Uuid = {3DFC333D-D198-4149-9824-BBBF6FD1F2D2}, Volume = {46}, Year = {2003}} @article{Sijen:2001, Abstract = {We have investigated the role of trigger RNA amplification during RNA interference (RNAi) in Caenorhabditis elegans. Analysis of small interfering RNAs (siRNAs) produced during RNAi in C. elegans revealed a substantial fraction that cannot derive directly from input dsRNA. Instead, a population of siRNAs (termed secondary siRNAs) appeared to derive from the action of a cellular RNA-directed RNA polymerase (RdRP) on mRNAs that are being targeted by the RNAi mechanism. The distribution of secondary siRNAs exhibited a distinct polarity (5'-->3'on the antisense strand), suggesting a cyclic amplification process in which RdRP is primed by existing siRNAs. This amplification mechanism substantially augments the potency of RNAi-based surveillance, while ensuring that the RNAi machinery will focus on expressed mRNAs. 0092-8674 Journal Article}, Author = {Sijen, T. and Fleenor, J. and Simmer, F. and Thijssen, K. L. and Parrish, S. and Timmons, L. and Plasterk, R. H. and Fire, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Cell}, Keywords = {Ribonuclease III;Animals;Transcription Factors/genetics/*physiology;Endoribonucleases/physiology;Animals, Genetically Modified;23 Technique;RNA, Small Interfering;RNA, Double-Stranded/*physiology;Support, Non-U.S. Gov't;Recombinant Fusion Proteins/physiology;RNA-Directed DNA Polymerase/*physiology;Sequence Deletion;RNA, Untranslated/*physiology;T abstr;RNA, Helminth/*physiology;Support, U.S. Gov't, P.H.S.;*Models, Genetic;Helminth Proteins/genetics/*physiology;Caenorhabditis elegans/embryology/*genetics;Gene Silencing/*physiology;Transgenes}, Number = {4}, Organization = {Hubrecht Laboratory, Center for Biomedical Genetics, Uppsalalaan 8, 3584 CT, Utrecht, The Netherlands.}, Pages = {465-76}, Pubmed = {11719187}, Title = {On the role of RNA amplification in dsRNA-triggered gene silencing}, Uuid = {ADDC3CDA-DBBA-4A89-BA04-4685BCEA6F0A}, Volume = {107}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11719187}} @article{Silberberg:2004, Abstract = {Information processing in neocortex can be very fast, indicating that neuronal ensembles faithfully transmit rapidly changing signals to each other. Apart from signal-to-noise issues, population codes are fundamentally constrained by the neuronal dynamics. In particular, the biophysical properties of individual neurons and collective phenomena may substantially limit the speed at which a graded signal can be represented by the activity of an ensemble. These implications of the neuronal dynamics are rarely studied experimentally. Here, we combine theoretical analysis and whole cell recordings to show that encoding signals in the variance of uncorrelated synaptic inputs to a neocortical ensemble enables faithful transmission of graded signals with high temporal resolution. In contrast, the encoding of signals in the mean current is subject to low-pass filtering.}, Author = {Silberberg, G. and Bethge, M. and Markram, H. and Pawelzik, K. and Tsodyks, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Research Support, Non-U.S. Gov't;21 Neurophysiology;Models, Neurological;Neocortex;Research Support, U.S. Gov't, Non-P.H.S.;21 Cortical oscillations;24 Pubmed search results 2008;Neurons}, Month = {2}, Nlm_Id = {0375404}, Number = {2}, Organization = {Department of Neurobiology, The Weizmann Institute of Science, Rehovot, 76100, Israel.}, Pages = {704-9}, Pii = {91/2/704}, Pubmed = {14762148}, Title = {Dynamics of population rate codes in ensembles of neocortical neurons}, Uuid = {9F13617B-6D3A-4E08-855A-4764F8E7022F}, Volume = {91}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00415.2003}} @article{Silberberg:2005, Abstract = {The functions performed by different neural microcircuits depend on the anatomical and physiological properties of the various synaptic pathways connecting neurons. Neural microcircuits across various species and brain regions are similar in terms of their repertoire of neurotransmitters, their synaptic kinetics, their short-term and long-term plasticity, and the target-specificity of their synaptic connections. However, microcircuits can be fundamentally different in terms of the precise recurrent design used to achieve a specific functionality. In this review, which is part of the TINS Microcircuits Special Feature, we compare the connectivity designs in spinal, hippocampal, neocortical and cerebellar microcircuits, and discuss the different computational challenges that each microcircuit faces.}, Author = {Silberberg, Gilad and Grillner, Sten and LeBeau, Fiona E. N. and Maex, Reinoud and Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Synapses;Research Support, Non-U.S. Gov't;21 Neurophysiology;Models, Neurological;21 Circuit structure-function;Spinal Cord;Synaptic Transmission;Nerve Net;Animals;Brain;24 Pubmed search results 2008;review}, Month = {10}, Nlm_Id = {7808616}, Number = {10}, Organization = {Nobel Institute for Neurophysiology, Department of Neuroscience, Karolinska Institutet, S-17177 Stockholm, Sweden.}, Pages = {541-51}, Pii = {S0166-2236(05)00212-2}, Pubmed = {16122815}, Title = {Synaptic pathways in neural microcircuits}, Uuid = {E56D4E7E-DAB9-4F5A-8C9D-4DE85714DC6D}, Volume = {28}, Year = {2005}, url = {papers/Silberberg_TrendsNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2005.08.004}} @article{Silva:2002, Abstract = {Progenitor cells in the early developing nervous system can divide symmetrically, giving rise to two daughter cells that divide again, or asymmetrically, giving rise to one cell that differentiates and one that divides again. It has been suggested that the orientation of the cell cleavage plane during mitosis determines the type of division. A marker of early cell differentiation, the RA4 antigen, was used to identify regions of the developing chick retina with and without differentiating cells, and the orientation of the cleavage plane was characterized for mitotic figures in each region. No difference was found in the frequency of any orientation between the regions with or without differentiating cells. Furthermore, in the region of the retina with differentiating cells, the RA4 antigen was present in mitotic figures with every possible orientation. Thus, the orientation of the cleavage plane appears to be unrelated to whether or not a division produces a cell that differentiates. It has also been suggested that the intracellular protein Numb mediates neurogenesis via asymmetric localization during cell division. Numb localization was compared with expression of markers of early cell differentiation, the RA4 antigen and Delta. Differentiating and nondifferentiating cells were found both with and without Numb expression. Cells with a cleavage plane parallel to the retinal surface were polarized, such that Numb and/or the RA4 antigen, when present, were only in the daughter cell farthest from the ventricle. These findings indicate a need to reconsider current hypotheses regarding the key features underlying symmetric and asymmetric divisions in the developing nervous system. 22184307 1529-2401 Journal Article}, Author = {Silva, A. O. and Ercole, C. E. and McLoon, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:58 -0400}, Journal = {J Neurosci}, Keywords = {Juvenile Hormones/*biosynthesis;Cell Division/physiology;10 Development;Mitosis/physiology;Cell Differentiation/*physiology;Retina/*cytology/*embryology/metabolism;Immunohistochemistry;F both;Antigens, Differentiation/biosynthesis;Cell Polarity/physiology;Chick Embryo;Animal;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Specific Pathogen-Free Organisms}, Number = {17}, Organization = {Department of Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.}, Pages = {7518-25}, Title = {Plane of cell cleavage and numb distribution during cell division relative to cell differentiation in the developing retina}, Uuid = {1BA9346B-06BD-4A6F-9BBC-D35814A77BD2}, Volume = {22}, Year = {2002}, url = {papers/Silva_JNeurosci2002.pdf}} @article{Silva:1991, Abstract = {Rhythmic activity in the neocortex varies with different behavioral and pathological states and in some cases may encode sensory information. However, the neural mechanisms of these oscillations are largely unknown. Many pyramidal neurons in layer 5 of the neocortex showed prolonged, 5- to 12-hertz rhythmic firing patterns at threshold. Rhythmic firing was due to intrinsic membrane properties, sodium conductances were essential for rhythmicity, and calcium-dependent conductances strongly modified rhythmicity. Isolated slices of neocortex generated epochs of 4- to 10-hertz synchronized activity when N-methyl-D-aspartate receptor-mediated channels were facilitated. Layer 5 was both necessary and sufficient to produce these synchronized oscillations. Thus, synaptic networks of intrinsically rhythmic neurons in layer 5 may generate or promote certain synchronized oscillations of the neocortex.}, Author = {Silva, L. R. and Amitai, Y. and Connors, B. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {21 Cortical oscillations;24 Pubmed search results 2008;Electroencephalography;Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Research Support, U.S. Gov't, P.H.S.;Calcium;Pyramidal Tracts;Culture Techniques;Sodium;Receptors, N-Methyl-D-Aspartate;Animals;Cerebral Cortex;Neurons;Membrane Potentials}, Medline = {91111102}, Month = {1}, Nlm_Id = {0404511}, Number = {4992}, Organization = {Section of Neurobiology, Brown University, Providence, RI 02912.}, Pages = {432-5}, Pubmed = {1824881}, Title = {Intrinsic oscillations of neocortex generated by layer 5 pyramidal neurons}, Uuid = {127864FC-7E81-4272-9458-A76E4EBA7660}, Volume = {251}, Year = {1991}} @article{Silver:2007, Abstract = {The ability to tackle analysis of the brain at multiple levels simultaneously is emerging from rapid methodological developments. The classical research strategies of "measure," "model," and "make" are being applied to the exploration of nervous system function. These include novel conceptual and theoretical approaches, creative use of mathematical modeling, and attempts to build brain-like devices and systems, as well as other developments including instrumentation and statistical modeling (not covered here). Increasingly, these efforts require teams of scientists from a variety of traditional scientific disciplines to work together. The potential of such efforts for understanding directed motor movement, emergence of cognitive function from neuronal activity, and development of neuromimetic computers are described by a team that includes individuals experienced in behavior and neuroscience, mathematics, and engineering. Funding agencies, including the National Science Foundation, explore the potential of these changing frontiers of research for developing research policies and long-term planning.}, Author = {Silver, Rae and Boahen, Kwabena and Grillner, Sten and Kopell, Nancy and Olsen, Kathie L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Models, Biological;20 Networks;Computational Biology;research support, non-u.s. gov't;23 Technique;24 Pubmed search results 2008;Biomedical Enhancement;Mental Processes;Neurosciences;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;Brain Mapping;Animals;Brain;Behaviorism;review;Humans}, Month = {10}, Nlm_Id = {8102140}, Number = {44}, Organization = {Psychology Department, Barnard College of Columbia University, New York, New York 10027, USA. qr\@columbia.edu}, Pages = {11807-19}, Pii = {27/44/11807}, Pubmed = {17978017}, Title = {Neurotech for neuroscience: unifying concepts, organizing principles, and emerging tools}, Uuid = {4A0611B0-629C-4C4E-A8FC-A7B3D560E2AF}, Volume = {27}, Year = {2007}, url = {papers/Silver_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3575-07.2007}} @article{Silver:2004, Abstract = {1471-003x Journal Article}, Author = {Silver, J. and Miller, J. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {G, L pdf;11 Glia}, Number = {2}, Organization = {Department of Neurosciences, School of Medicine, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, Ohio 44106, USA. jxs10\@cwru.edu}, Pages = {146-56}, Title = {Regeneration beyond the glial scar}, Uuid = {C45FF0A6-E32E-43C6-879F-1F4074B3F210}, Volume = {5}, Year = {2004}, url = {papers/Silver_NatRevNeurosci2004.pdf}} @article{Sim:2006, Abstract = {Central neurocytoma (CN) is a rare periventricular tumor, whose derivation, lineage potential, and molecular regulation have been mostly unexplored. We noted that CN cells exhibited an antigenic profile typical of neuronal progenitor cells in vivo, yet in vitro generated neurospheres, divided in response to bFGF (basic fibroblast growth factor), activated the neuroepithelial enhancer of the nestin gene, and gave rise to both neuron-like cells and astrocytes. When CN gene expression was compared with that of both normal adult VZ (ventricular zone) and E/nestin:GFP (green fluorescent protein)-sorted native neuronal progenitors, significant overlap was noted. Marker analysis suggested that the gene expression pattern of CN was that of a proneuronal population; glial markers were conspicuously absent, suggesting that the emergence of astroglia from CN occurred only with passage. The expression pattern of CN was distinguished from that of native progenitor cells by a cohort of differentially expressed genes potentially involved in both the oncogenesis and phenotypic restriction of neurocytoma. These included both IGF2 and several components of its signaling pathway, whose sharp overexpression implicated dysregulated autocrine IGF2 signaling in CN oncogenesis. Both receptors and effectors of canonical wnt signaling, as well as GDF8 (growth differentiation factor 8), PDGF-D, and neuregulin, were differentially overexpressed by CN, suggesting that CN is characterized by the concurrent overactivation of these pathways, which may serve to drive neurocytoma expansion while restricting tumor progenitor phenotype. This strategy of comparing the gene expression of tumor cells to that of the purified native progenitors from which they derive may provide a focused approach to identifying transcripts important to stem and progenitor cell oncogenesis.}, Author = {Sim, Fraser J. and Keyoung, H. Michael and Goldman, James E. and Kim, Dong Kyu and Jung, Hee-Won W. and Roy, Neeta S. and Goldman, Steven A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Tumor Cells, Cultured;Adult;Neurocytoma;Stem Cells;comparative study;research support, n.i.h., extramural;Humans;Male;24 Pubmed search results 2008;Neurons}, Month = {11}, Nlm_Id = {8102140}, Number = {48}, Organization = {Department of Neurology, University of Rochester Medical Center, Rochester, New York 14642, USA.}, Pages = {12544-55}, Pii = {26/48/12544}, Pubmed = {17135416}, Title = {Neurocytoma is a tumor of adult neuronal progenitor cells}, Uuid = {271E2B6E-0735-4776-9D0C-C8983709D86C}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0829-06.2006}} @article{Simard:2004, Abstract = {Pluripotent stem cells can differentiate into a variety of cell types during tissue development and regeneration. However, it is still unclear whether bone marrow-derived stem cells can migrate across the blood-brain barrier in many regions of the central nervous system (CNS) and if these cells can readily differentiate into functional parenchymal microglia. We thus studied the differentiation fate of bone marrow stem cells upon immigration into the CNS. To this end, we systemically transplanted stem cells that express green fluorescent protein (GFP) into lethally irradiated mice and found that these cells immigrated into the brain parenchyma of many regions of the CNS. Nearly all of the infiltrating cells had a highly ramified morphology and colocalized with the microglial marker iba1. Moreover, these cells expressed high levels of the protein CD11c, indicating that microglia of bone marrow origin may be potent antigen presenting cells. These data suggest that microglia of blood origin could activate cells of the adaptive immune system and cause harm to the CNS. Therefore, these results may have great clinical relevance for both immune-derived neuronal disorders and cancer patients undergoing allogeneic hematopoietic stem-cell transplantation.}, Author = {Simard, Alain R. and Rivest, Serge}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {Cell Differentiation;Research Support, Non-U.S. Gov't;Central Nervous System;Bone Marrow Cells;Multipotent Stem Cells;Mice, Inbred C57BL;Stem Cells;Bone Marrow Transplantation;11 Glia;Microglia;Antigen-Presenting Cells;Animals;Cell Movement;Mice;Stem Cell Transplantation;Cell Lineage}, Month = {6}, Nlm_Id = {8804484}, Number = {9}, Organization = {Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, Qu{\'e}bec, Canada.}, Pages = {998-1000}, Pii = {04-1517fje}, Pubmed = {15084516}, Title = {Bone marrow stem cells have the ability to populate the entire central nervous system into fully differentiated parenchymal microglia}, Uuid = {8481DE10-D3B7-11D9-A0E9-000D9346EC2A}, Volume = {18}, Year = {2004}, url = {papers/Simard_FASEBJ2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.04-1517fje}} @article{Simard:2006, Abstract = {Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the beta-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune reaction to both exogenous and endogenous beta-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed us to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia are thus very efficient in restricting amyloid deposits. Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques.}, Author = {Simard, Alain R. and Soulet, Denis and Gowing, Genevieve and Julien, Jean-Pierre P. and Rivest, Serge}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Alzheimer Disease;research support, non-u.s. gov't ;Peptide Fragments;Disease Models, Animal;24 Pubmed search results 2008;Green Fluorescent Proteins;Amyloid beta-Protein Precursor;Immunohistochemistry;Lysosomal-Associated Membrane Protein 2;Calcium-Binding Proteins;Animals;Cells, Cultured;Age Factors;Phagocytosis;Whole-Body Irradiation;Injections, Intraventricular;comparative study ;Amyloid beta-Protein;Imaging, Three-Dimensional;Gene Expression;Presenilin-1;Interleukin-1;Bone Marrow Transplantation;Mice, Inbred C57BL;RNA, Messenger;In Situ Hybridization;Toll-Like Receptor 2;Senile Plaques;11 Glia;comparative study;Tumor Necrosis Factor-alpha;Antigens, CD46;Indoles;Time Factors;Membrane Proteins;Bone Marrow Cells;Microglia;research support, non-u.s. gov't;Microscopy, Confocal;Mice;Humans;Mice, Transgenic}, Month = {2}, Nlm_Id = {8809320}, Number = {4}, Organization = {Laboratory of Molecular Endocrinology, CHUL Research Center and Department of Anatomy and Physiology, Laval University, 2705 Laurier boul., Qu{\'e}bec G1V 4G2, Canada.}, Pages = {489-502}, Pii = {S0896-6273(06)00075-4}, Pubmed = {16476660}, Title = {Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease}, Uuid = {E2375546-D015-4E0A-A2ED-F431F11D6B00}, Volume = {49}, Year = {2006}, url = {papers/Simard_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.01.022}} @article{Simpson:2000, Abstract = {Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) characterised by perivascular inflammatory cell infiltrates and plaques of demyelination. Chemokines have been shown to play an important role in the activation and directional migration of cells to sites of CNS inflammation. The action of chemokines requires the expression of their complementary chemokine receptors by their target cells. We have examined the expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in post-mortem MS CNS tissue using single- and double-labelling immunocytochemistry techniques. Low levels of CCR2, CCR3 and CCR5 were expressed by microglial cells throughout control CNS tissue. In chronic active MS lesions CCR2, CCR3 and CCR5 were associated with foamy macrophages and activated microglia. CCR2 and CCR5 were also present on large numbers of infiltrating lymphocytes. A smaller number of CCR3-positive lymphocytes were present, but we also noted CCR3 and CCR5 on astrocytes in five of the 14 cases of MS investigated, particularly associated with processes around vessels and at the glia limitans. Ligands for CCR2 and CCR3 include MCP-1 and MCP-3 which were co-localised around vessels with the infiltrating leukocytes, but were also present in unaffected areas of cortex. The elevated expression of CCR2, CCR3 and CCR5 in the CNS in MS suggests these beta-chemokine receptors and their ligands play a role in the pathogenesis of MS.}, Author = {Simpson, J. and Rezaie, P. and Newcombe, J. and Cuzner, M. L. and Male, D. and Woodroofe, M. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Ligands;Research Support, Non-U.S. Gov't;Multiple Sclerosis;Astrocytes;Humans;Macrophages;Middle Aged;Disease Progression;Microglia;Female;11 Glia;Chemotaxis, Leukocyte;Chronic Disease;Male;Aged;Monocyte Chemoattractant Proteins;Antibody Specificity;Matched-Pair Analysis;Receptors, Chemokine;Aged, 80 and over;Adult;Receptors, CCR5;CD4-Positive T-Lymphocytes;Central Nervous System;Monocyte Chemoattractant Protein-1;Immunohistochemistry;Inflammation;Recurrence;Cytokines}, Medline = {20361893}, Month = {8}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Biomedical Research Centre and Division of Biomedical Sciences, Sheffield Hallam University, City Campus, Pond Street, South Yorkshire, S1 1WB, Sheffield, UK.}, Pages = {192-200}, Pii = {S0165572800002745}, Pubmed = {10900353}, Title = {Expression of the beta-chemokine receptors CCR2, CCR3 and CCR5 in multiple sclerosis central nervous system tissue}, Uuid = {1A944190-B640-4087-8951-1EF4E40A2CB9}, Volume = {108}, Year = {2000}} @article{Sinclair:1999, Abstract = {The yield of surviving dopamine cells in nigral grafts is typically low. It is unclear whether the dopamine neurons that do survive are postmitotic at the time of implantation, or are precursor cells that differentiate into dopamine neurons following transplantation in the host brain. We have therefore compared the survival of dopamine neurons in grafts that have been labelled with BrdU at different times prior to or following implantation in order to identify those cells that undergo final cell division at each stage of the procedure. Seven groups of rats were prepared with unilateral nigrostriatal lesions. Three groups received nigral grafts derived from E14 embryos labelled with BrdU in utero on either E12, E13 or E14 days of embryonic age (the E14 injection made 2 h prior to preparation of the graft cell suspension). Three further groups received nigral grafts from untreated E14 embryos, and then dividing cells within the grafts were labelled by injection of BrdU into the host lateral ventricle, 2 h, 1 day or 2 days after implantation (equivalent to E14, E15 and E16 days of embryonic age). The control group received standard (unlabelled) E14 grafts. Five weeks after the transplantation surgery, the host brains were processed using double immunohistochemical techniques to detect tyrosine hydroxylase (TH)-positive neurons which had incorporated BrdU. In the grafts labelled with BrdU prior to implantation, there was an increasing proportion of double-labelled cells (out of the total TH-positive cells surviving in the grafts) with birth dates on E12, E13 and E14 (1\%, 12\%and 10\%per day, respectively). By contrast, grafts labelled following implantation, although containing many dividing neurons, had very few of these BrdU-labelled cells expressing a dopaminergic phenotype; < 1\%surviving TH-positive cells were double-labelled from the 2 h post-transplant injection, and < 0.1\%from each subsequent injection. This suggests not only that the great majority of TH-positive neurons in nigral grafts were already differentiated at the time of implantation, but also that transplantation of E14 ventral mesencephalic tissue either kills dopaminergic precursors or (more likely in our opinion) prevents their differentiation into a dopaminergic phenotype. Precursor cells that would differentiate into dopaminergic neurons beyond E14 if left in situ in the intact ventral mesencephalon do not readily differentiate into mature dopamine neurons following transplantation. If we are to enhance yields of functional dopamine-rich transplants, then we must identify strategies both to protect predifferentiated dopamine neurons in the grafts and to promote differentiation of a dopaminergic phenotype in precursor cells that continue to divide within the grafts following transplantation into an adult host environment.}, Author = {Sinclair, S. R. and Fawcett, J. W. and Dunnett, S. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Cell Survival;Cell Differentiation;Dopamine;Animals;Brain Tissue Transplantation;Rats;Female;Substantia Nigra;Fetal Tissue Transplantation;Embryo;Rats, Inbred F344;Neurons;Tyrosine 3-Monooxygenase;Cell Division;24 Pubmed search results 2008;Bromodeoxyuridine;Immunohistochemistry;Graft Survival;Oxidopamine;Research Support, Non-U.S. Gov't}, Medline = {20062501}, Month = {12}, Nlm_Id = {8918110}, Number = {12}, Organization = {Center for Brain Repair, Cambridge, UK.}, Pages = {4341-8}, Pii = {ejn867}, Pubmed = {10594660}, Title = {Dopamine cells in nigral grafts differentiate prior to implantation}, Uuid = {B35168F2-42EC-4DD6-8B29-3EB1773D37C2}, Volume = {11}, Year = {1999}} @article{Sinclair:1997, Abstract = {Retroviral vectors have had limited success in mediating gene transfer to hematopoietic stem cells, particularly in primates, due in part to low or absent expression of the amphotropic receptor (RAM-1). We have been interested in determining whether retrovirus pseudotyped with vesicular stomatitis virus G protein (VSV-G) would allow more efficient gene delivery to hematopoietic stem cells as the VSV-G receptors appear to be ubiquitously present phospholipids. However, we previously found that completion of retroviral vector reverse transcription does not occur in CD34+ CD38- hematopoietic stem cells that were exposed to VSV-G pseudotyped retrovirus. To determine at which stage the block to infection of CD34+ CD38- cells occurs, we confirmed by FACS analysis that VSV-G pseudotyped viral particles could bind to CD34+ CD38- cells. Virus binding to CD34+ cells was saturable at 4 degrees C but nonsaturable at 37 degrees C, up to a multiplicity of infection of 1080. This suggests that surface levels of phospholipid receptors available for viral binding are limiting on CD34+ cells. Cytokine stimulation increased virus binding to CD34+ cells. However, no increase in the level of surface phosphatidylserine (PS), a strong candidate for the VSV-G receptor, was seen as detected by the PS-specific reagent, annexin V. This suggests that another molecule is serving as the VSV-G receptor on CD34+ cells. Here, we show that once virus binding to cytokine-stimulated CD34+ CD38- cells has occurred, virus fusion proceeds efficiently as determined by octadecyl rhodamine (R18) fusion assays. Taken together with our previous observation that reverse transcription does not occur in CD34+ CD38- cells, we suggest that there are intracellular mechanisms leading to blockage of complete reverse transcription of the retrovirus in CD34+ CD38- cells. This has important implications for retrovirus-mediated gene transfer to quiescent stem cells.}, Author = {Sinclair, A. M. and Agrawal, Y. P. and Elbar, E. and Agrawal, R. and Ho, A. D. and Levine, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Flow Cytometry;Virus Diseases;Research Support, Non-U.S. Gov't;ADP-ribosyl Cyclase;Hematopoietic Stem Cells;Antigens, Differentiation;Research Support, U.S. Gov't, P.H.S.;Annexin A5;Retroviridae;Antigens, CD;Antigens, CD34;Vesicular stomatitis-Indiana virus;Gene Therapy;NAD+ Nucleosidase;Humans;15 Retrovirus mechanism;Genetic Vectors}, Medline = {98010141}, Month = {9}, Nlm_Id = {9421525}, Number = {9}, Organization = {Department of Haematology, University of Cambridge, MRC Center, UK.}, Pages = {918-27}, Pubmed = {9349428}, Title = {Interaction of vesicular stomatitis virus-G pseudotyped retrovirus with CD34+ and CD34+ CD38- hematopoietic progenitor cells}, Uuid = {15A95DC0-C7C0-4ED1-A32C-6F4641519503}, Volume = {4}, Year = {1997}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3300479}} @article{Singh:2008, Abstract = {The mechanisms that regulate the pruning of mammalian axons are just now being elucidated. Here, we describe a mechanism by which, during developmental sympathetic axon competition, winning axons secrete brain-derived neurotrophic factor (BDNF) in an activity-dependent fashion, which binds to the p75 neurotrophin receptor (p75NTR) on losing axons to cause their degeneration and, ultimately, axon pruning. Specifically, we found that pruning of rat and mouse sympathetic axons that project to the eye requires both activity-dependent BDNF and p75NTR. p75NTR and BDNF are also essential for activity-dependent axon pruning in culture, where they mediate pruning by directly causing axon degeneration. p75NTR, which is enriched in losing axons, causes axonal degeneration by suppressing TrkA-mediated signaling that is essential for axonal maintenance. These data provide a mechanism that explains how active axons can eliminate less-active, competing axons during developmental pruning by directly promoting p75NTR-mediated axonal degeneration.}, Author = {Singh, Karun K. and Park, Katya J. and Hong, Elizabeth J. and Kramer, Bianca M. and Greenberg, Michael E. and Kaplan, David R. and Miller, Freda D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Cholera Toxin;Dose-Response Relationship, Drug;Nerve Degeneration;Animals;Cells, Cultured;Gene Expression Regulation, Developmental;Rats;Enzyme Inhibitors;Nerve Growth Factor;Brain-Derived Neurotrophic Factor;Visual Pathways;Axons;Rats, Sprague-Dawley;Mice, Transgenic;Mice, Inbred C57BL;Potassium Chloride;research support, non-u.s. gov't;Green Fluorescent Proteins;Stilbamidines;Animals, Newborn;Axotomy;Neurons;Superior Cervical Ganglion;Receptor, Nerve Growth Factor;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Drug Interactions}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {Developmental and Stem Cell Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Canada M5G 1X8.}, Pages = {649-58}, Pii = {nn.2114}, Pubmed = {18382462}, Title = {Developmental axon pruning mediated by BDNF-p75NTR-dependent axon degeneration}, Uuid = {F293B6FC-FAFF-4823-B0EF-F8D81450C953}, Volume = {11}, Year = {2008}, url = {papers/Singh_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2114}} @article{Singh:1996, Abstract = {Vectors based on murine C-type retroviruses are commonly used in biology. The efficiency of viral infection is normally increased by a facilitator, for example polybrene, DEAE-dextran or a liposome. The receptor for ecotropic viruses is a transporter for basic amino acids; we therefore explored the use of a highly basic protein, histone type IIA, as a facilitator. We show in several cell types that histone is as efficient as the other agents tested, and in some cases more so. This readily available reagent is thus likely to be useful in the wide range of studies that employ retroviral vectors. 0305-1048 Journal Article}, Author = {Singh, D. and Rigby, P. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Nucleic Acids Res}, Keywords = {*Gene Transfer Techniques;*Genetic Vectors;*Receptors, Virus;Biological Transport/drug effects;Amino Acids, Diamino/metabolism;*Membrane Glycoproteins;Membrane Proteins/drug effects;Carrier Proteins/drug effects;J;Gammaretrovirus/*genetics/pathogenicity;15 Retrovirus mechanism;Cells, Cultured;Animals;Support, Non-U.S. Gov't;Mice;Histones/*pharmacology}, Number = {15}, Organization = {Division of Eukaryotic Molecular Genetics, MRC National Institute for Medical Research, London, UK.}, Pages = {3113-4}, Pubmed = {8760902}, Title = {The use of histone as a facilitator to improve the efficiency of retroviral gene transfer}, Uuid = {6103ABFA-20B2-4ADB-B4CF-60DA80F3D161}, Volume = {24}, Year = {1996}, url = {papers/Singh_NucleicAcidsRes1996.pdf}} @article{Siolas:2005, Abstract = {Designing potent silencing triggers is key to the successful application of RNA interference (RNAi) in mammals. Recent studies suggest that the assembly of RNAi effector complexes is coupled to Dicer cleavage. Here we examine whether transfection of optimized Dicer substrates results in an improved RNAi response. Dicer cleavage of chemically synthesized short hairpin RNAs (shRNAs) with 29-base-pair stems and 2-nucleotide 3' overhangs produced predictable homogeneous small RNAs comprising the 22 bases at the 3' end of the stem. Consequently, direct comparisons of synthetic small interfering RNAs and shRNAs that yield the same small RNA became possible. We found synthetic 29-mer shRNAs to be more potent inducers of RNAi than small interfering RNAs. Maximal inhibition of target genes was achieved at lower concentrations and silencing at 24 h was often greater. These studies provide the basis for an improved approach to triggering experimental silencing via the RNAi pathway.}, Author = {Siolas, Despina and Lerner, Cara and Burchard, Julja and Ge, Wei and Linsley, Peter S. and Paddison, Patrick J. and Hannon, Gregory J. and Cleary, Michele A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {23 RNAi;23 Technique}, Month = {2}, Nlm_Id = {9604648}, Number = {2}, Organization = {[1] Program in Genetics, Stony Brook University, Stony Brook, New York 11794, USA. [2] Cold Spring Harbor Laboratory, Watson School of Biological Sciences, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.}, Pages = {227-31}, Pii = {nbt1052}, Pubmed = {15619616}, Title = {Synthetic shRNAs as potent RNAi triggers}, Uuid = {2956939B-1F08-404B-846C-5F52A9EF2C64}, Volume = {23}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt1052}} @article{Sioud:2006, Author = {Sioud, Mouldy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {news;Models, Biological;RNA, Messenger;RNA, Small Interfering;23 Technique;Inflammation;Cell Line;Signal Transduction;RNA Interference;comment;RNA, Viral;Animals;Humans;24 Pubmed search results 2008;Immune System;Cytoplasm}, Month = {5}, Nlm_Id = {9604648}, Number = {5}, Pages = {521-2}, Pii = {nbt0506-521}, Pubmed = {16680132}, Title = {RNA interference below the immune radar}, Uuid = {81F9AFB3-C704-4FB5-9697-968D619E09D8}, Volume = {24}, Year = {2006}, url = {papers/Sioud_NatBiotechnol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt0506-521}} @article{Sisodiya:2000, Abstract = {Malformations of cortical development (MCD) are responsible for many cases of refractory epilepsy in adults and children. The results of surgical treatment are difficult to assess from the published literature. Judging from the limited number of adequately reported cases, approximately 40\%of all cases of MCD treated surgically may be rendered seizure-free over a minimum 2-year follow-up period. This figure is the same for focal cortical dysplasia (FCD), the most common variety of MCD in surgical reports. In comparison with outcome for epilepsy associated with hippocampal sclerosis, this figure is low. Part of the difference may be artificial and related to limited reporting. Much of the difference is likely to relate to the complex underlying biology of MCD. Analysis of epileptogenesis in MCD has been undertaken. Different types of MCD have different sequelae. Some varieties are intrinsically epileptogenic; these include FCD and heterotopia. Although in most cases, the visualized MCD lies within the region of brain responsible for generating seizures (the epileptogenic zone), it may not constitute the entire epileptogenic zone in all cases. For polymicrogyria and schizencephaly in particular, the visualized abnormalities are probably not the most important component of the epileptogenic zone. There is evidence that the epileptogenic zone is spatially distributed and also, in some cases, temporally distributed. These findings may explain poor surgical outcome and the inadequacy of current presurgical evaluative methods. New preoperative techniques offer the opportunity of improved presurgical planning and selection of cases more likely to be rendered seizure-free by current surgical techniques. Of paramount importance is improved reporting. The establishment of a central registry may facilitate this aim. Specific recommendations are made for surgical strategies based on current experience and understanding.}, Author = {Sisodiya, S. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0006-8950}, Journal = {Brain}, Keywords = {Epilepsy;Brain Diseases;10 Development;21 Dysplasia-heterotopia;21 Neurophysiology;research support, non-u.s. gov't;Adult;10 genetics malformation;Child;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0372537}, Organization = {Epilepsy Research Group, Institute of Neurology, University College London, UK. sisodiya\@ion.ucl.ac.uk}, Pages = {1075-91}, Pubmed = {10825348}, Title = {Surgery for malformations of cortical development causing epilepsy}, Uuid = {214BD6AC-05E6-46D2-962C-FED5F1D99D4C}, Volume = {123 ( Pt 6)}, Year = {2000}, url = {papers/Sisodiya_Brain2000.pdf}} @article{Sisodiya:2004, Author = {Sisodiya, S. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1460-2156}, Journal = {Brain}, Keywords = {Epilepsy;Treatment Outcome;10 Development;10 genetics malformation;comment;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {0372537}, Number = {Pt 11}, Organization = {Department of Clinical and Experimental Epilepsy, Institute of Neurology, UCL, Queen Square, London WC1N 3BG, UK. sisodiya\@ion.ucl.ac.uk}, Pages = {2383-4}, Pii = {127/11/2383}, Pubmed = {15492113}, Title = {Surgery for focal cortical dysplasia}, Uuid = {A5926A12-F6A7-4E9E-A7C4-82A42B0B273C}, Volume = {127}, Year = {2004}, url = {papers/Sisodiya_Brain2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/brain/awh312}} @article{Sivasankaran:2004, Abstract = {Successful axon regeneration in the mammalian central nervous system (CNS) is at least partially compromised due to the inhibitors associated with myelin and glial scar. However, the intracellular signaling mechanisms underlying these inhibitory activities are largely unknown. Here we provide biochemical and functional evidence that conventional isoforms of protein kinase C (PKC) are key components in the signaling pathways that mediate the inhibitory activities of myelin components and chondroitin sulfate proteoglycans (CSPGs), the major class of inhibitors in the glial scar. Both the myelin inhibitors and CSPGs induce PKC activation. Blocking PKC activity pharmacologically and genetically attenuates the ability of CNS myelin and CSPGs to activate Rho and inhibit neurite outgrowth. Intrathecal infusion of a PKC inhibitor, Go6976, into the site of dorsal hemisection promotes regeneration of dorsal column axons across and beyond the lesion site in adult rats. Thus, perturbing PKC activity could represent a therapeutic approach to stimulating axon regeneration after brain and spinal cord injuries. 1097-6256 Journal Article}, Author = {Sivasankaran, R. and Pei, J. and Wang, K. C. and Zhang, Y. P. and Shields, C. B. and Xu, X. M. and He, Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Nat Neurosci}, Keywords = {G, L pdf;17 Transplant Regeneration;11 Glia}, Number = {3}, Organization = {Division of Neuroscience, 320 Longwood Avenue, Children's Hospital, Boston, Massachusetts 02115, USA.}, Pages = {261-8}, Title = {PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration}, Uuid = {67533739-7F6A-4536-A114-79F3D1C4B090}, Volume = {7}, Year = {2004}, url = {papers/Sivasankaran_NatNeurosci2004.pdf}} @article{Sjostrom:2002, Abstract = {Plasticity at central synapses depends critically on the timing of presynaptic and postsynaptic action potentials. Key initial steps in synaptic plasticity involve the back-propagation of action potentials into the dendritic tree and calcium influx that depends nonlinearly on the action potential and synaptic input. These initial steps are now better understood. In addition, recent studies of processes as diverse as gene expression and channel inactivation suggest that responses to calcium transients depend not only their amplitude, but on their time course and on the location of their origin. 0959-4388 Journal Article Review Review, Tutorial}, Author = {Sjostrom, P. J. and Nelson, S. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Curr Opin Neurobiol}, Keywords = {18 Classic Neuroanatomy Physiology;Synapses/*physiology/ultrastructure;Calcium Signaling/*physiology;Human;M;Neuronal Plasticity/*physiology;Support, U.S. Gov't, P.H.S.;Animals;Action Potentials/*physiology}, Number = {3}, Organization = {Department of Biology and Volen Center for Complex Systems, Brandeis University, Mailstop 008, 415 South Street, Waltham, Massachusetts 02454-9110, USA.}, Pages = {305-14}, Pubmed = {12049938}, Title = {Spike timing, calcium signals and synaptic plasticity}, Uuid = {6C69ADFC-C357-4A35-AF09-A2B96E1FB902}, Volume = {12}, Year = {2002}, url = {papers/Sjostrom_CurrOpinNeurobiol2002.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12049938}} @article{Sjostrom:2003, Abstract = {There is a consensus that NMDA receptors (NMDARs) detect coincident pre- and postsynaptic activity during induction of long-term potentiation (LTP), but their role in timing-dependent long-term depression (tLTD) is unclear. We examine tLTD in neocortical layer 5 (L5) pyramidal pairs and find that tLTD is expressed presynaptically, implying retrograde signaling. CB1 agonists produce depression that mimics and occludes tLTD. This agonist-induced LTD requires presynaptic activity and NMDAR activation, but not postsynaptic Ca(2+) influx. Further experiments demonstrate the existence of presynaptic NMDARs that underlie the presynaptic activity dependence. Finally, manipulating cannabinoid breakdown alters the temporal window for tLTD. In conclusion, tLTD requires simultaneous activation of presynaptic NMDA and CB1 receptors. This novel form of coincidence detection may explain the temporal window of tLTD and may also impart synapse specificity to cannabinoid retrograde signaling.}, Author = {Sj{\"o}str{\"o}m, Per Jesper and Turrigiano, Gina G. and Nelson, Sacha B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Long-Term Synaptic Depression;Signal Transduction;Rats, Long-Evans;Electrophysiology;Animals;Cells, Cultured;Rats;Receptors, Presynaptic;Neuronal Plasticity;Receptors, Cannabinoid;research support, u.s. gov't, p.h.s. ;Neocortex;Patch-Clamp Techniques;Long-Term Depression (Physiology);research support, non-u.s. gov't;Receptors, Drug;research support, non-u.s. gov't ;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {8809320}, Number = {4}, Organization = {Department of Biology, Volen Center for Complex Systems, Brandeis University, Mailstop 008, 415 South Street, Waltham, MA 02454, USA.}, Pages = {641-54}, Pii = {S0896627303004768}, Pubmed = {12925278}, Title = {Neocortical LTD via coincident activation of presynaptic NMDA and cannabinoid receptors}, Uuid = {686B5E49-3490-439B-AC02-8EDD4D87AEC0}, Volume = {39}, Year = {2003}, url = {papers/Sjöström_Neuron2003.pdf}} @article{Skeen:1986, Abstract = {Quantitative morphometric methods were used in mice to study the effect postnatal olfactory deprivation has on tufted cell size and number. The two layers containing tufted cells, the external plexiform and glomerular layers, are considerably smaller in the deprived olfactory bulbs than in the contralateral, experienced olfactory bulbs. While most of this volumetric deficit may be due to an attenuation of synaptogenesis and dendritic elaboration, an additional factor contributing to the reduced volume of these bulbar layers is a substantial loss of tufted cells. Since tufted cells are generated prenatally, their reduced number in the postnatally deprived olfactory bulb is probably a consequence of retarded migration or cell death. eng Journal Article}, Author = {Skeen, L. C. and Due, B. R. and Douglas, F. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Journal = {Neurosci Lett}, Keywords = {Olfactory Bulb/*cytology/physiology;*Cell Count;Animals, Newborn/*physiology;Cell Survival;Animal;Mice, Inbred ICR;Support, U.S. Gov't, P.H.S.;I abstr;Neurons/physiology;Mice;Cell Movement;13 Olfactory bulb anatomy;Sensory Deprivation/*physiology}, Number = {1}, Pages = {5-10.}, Title = {Neonatal sensory deprivation reduces tufted cell number in mouse olfactory bulbs}, Uuid = {A5CAD779-A840-4370-93EC-75D76E904547}, Volume = {63}, Year = {1986}} @article{Skinner:2001, Abstract = {Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disease caused by the expression of mutant ataxin-1 that contains an expanded polyglutamine tract. Overexpression of mutant ataxin-1 in Purkinje cells of transgenic mice results in a progressive ataxia and Purkinje cell pathology that are very similar to those seen in SCA1 patients. Two prominent aspects of pathology in the SCA1 mice are the presence of cytoplasmic vacuoles and dendritic atrophy. We found that the vacuoles in Purkinje cells seem to originate as large invaginations of the outer cell membrane. The cytoplasmic vacuoles contained proteins from the somatodendritic membrane, including mGluR1, GluRDelta1/Delta2, GluR2/3, and protein kinase C (PKC) gamma. Further examination of PKCgamma revealed that its sequestration into cytoplasmic vacuoles was accompanied by concurrent loss of PKCgamma localization at the Purkinje cell dendritic membrane and decreased detection of PKCgamma by Western blot analysis. In addition, the vacuoles were immunoreactive for components of the ubiquitin/proteasome degradative pathway. These findings present a link between vacuole formation and loss of dendrites in Purkinje cells of SCA1 mice and indicate that altered somatodendritic membrane trafficking and loss of proteins including PKCgamma, are a part of the neuronal dysfunction in SCA1 transgenic mice.}, Author = {Skinner, P. J. and Vierra-Green, C. A. and Clark, H. B. and Zoghbi, H. Y. and Orr, H. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Protein Kinase C;Purkinje Cells;Tissue Distribution;Animals;Ubiquitins;Cytoplasm;Mice, Transgenic;Cysteine Endopeptidases;Not relevant;11 Glia;Multienzyme Complexes;Dendrites;Support, U.S. Gov't, P.H.S.;Nuclear Proteins;Mice;Receptors, Metabotropic Glutamate;Isoenzymes;Intracellular Membranes;Nerve Tissue Proteins;Membrane Proteins}, Medline = {21433386}, Month = {9}, Nlm_Id = {0370502}, Number = {3}, Organization = {Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA.}, Pages = {905-13}, Pubmed = {11549583}, Title = {Altered trafficking of membrane proteins in purkinje cells of SCA1 transgenic mice}, Uuid = {1168F850-1F71-4671-AE9F-E6B32973047B}, Volume = {159}, Year = {2001}, url = {papers/Skinner_AmJPathol2001.pdf}} @article{Skupski:1999, Abstract = {During 1998 the primary focus of the Genome Sequence DataBase (GSDB; http://www.ncgr.org/gsdb ) located at the National Center for Genome Resources (NCGR) has been to improve data quality, improve data collections, and provide new methods and tools to access and analyze data. Data quality has been improved by extensive curation of certain data fields necessary for maintaining data collections and for using certain tools. Data quality has also been increased by improvements to the suite of programs that import data from the International Nucleotide Sequence Database Collaboration (IC). The Sequence Tag Alignment and Consensus Knowledgebase (STACK), a database of human expressed gene sequences developed by the South African National Bioinformatics Institute (SANBI), became available within the last year, allowing public access to this valuable resource of expressed sequences. Data access was improved by the addition of the Sequence Viewer, a platform-independent graphical viewer for GSDB sequence data. This tool has also been integrated with other searching and data retrieval tools. A BLAST homology search service was also made available, allowing researchers to search all of the data, including the unique data, that are available from GSDB. These improvements are designed to make GSDB more accessible to users, extend the rich searching capability already present in GSDB, and to facilitate the transition to an integrated system containing many different types of biological data.}, Author = {Skupski, M. P. and Booker, M. and Farmer, A. and Harpold, M. and Huang, W. and Inman, J. and Kiphart, D. and Kodira, C. and Root, S. and Schilkey, F. and Schwertfeger, J. and Siepel, A. and Stamper, D. and Thayer, N. and Thompson, R. and Wortman, J. and Zhuang, J. J. and Harger, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0305-1048}, Journal = {Nucleic Acids Res}, Keywords = {Computational Biology;Base Sequence;Databases, Factual;Human;Sequence Alignment;Genome, Human;Gene Expression;Support, U.S. Gov't, Non-P.H.S.;Genome;Animals;Information Storage and Retrieval;Consensus Sequence;23 Technique}, Medline = {99063647}, Month = {1}, Nlm_Id = {0411011}, Number = {1}, Organization = {National Center for Genome Resources, 1800 Old Pecos Trail, Suite A, Santa Fe, NM 87505, USA.}, Pages = {35-8}, Pii = {gkc104}, Pubmed = {9847136}, Title = {The Genome Sequence DataBase: towards an integrated functional genomics resource}, Uuid = {3E6094C4-D474-42AA-94E3-9340C922F20B}, Volume = {27}, Year = {1999}} @article{Slobodov:2001, Abstract = {Injury and demyelinating diseases result in the disruption of the myelin sheath that surrounds axons in the nervous system. The removal of degenerating myelin by macrophages and microglia is central to repair mechanisms that follow. The efficiency of myelin removal depends on magnitudes and rates of myelin phagocytosis and degradation. In the present study we test whether environmental conditions within a tissue can control patterns of myelin removal. We document that macrophages that are recruited to the same tissue but by distinct inflammatory stimuli differ in their ability to phagocytose and degrade myelin. These observations may apply to the nervous system where different pathological conditions that involve distinct inflammatory stimuli may induce different functional states in microglia and macrophages.}, Author = {Slobodov, U. and Reichert, F. and Mirski, R. and Rotshenker, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Macrophages, Peritoneal;Phagocytosis;Animals;Myelin Sheath;Cells, Cultured;Myelin Basic Proteins;Mice, Inbred C57BL;Not relevant;11 Glia;Microscopy, Fluorescence;Cell Adhesion;Support, Non-U.S. Gov't;Macrophage-1 Antigen;Support, U.S. Gov't, Non-P.H.S.;Mice;Enzyme-Linked Immunosorbent Assay;Immunohistochemistry;Inflammation}, Medline = {21099727}, Month = {2}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Anatomy and Cell Biology, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.}, Pages = {401-9}, Pii = {S0014488600975599}, Pubmed = {11161629}, Title = {Distinct inflammatory stimuli induce different patterns of myelin phagocytosis and degradation in recruited macrophages}, Uuid = {7F35B0EE-801B-4275-8642-7729784263A0}, Volume = {167}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/exnr.2000.7559}} @article{Smart:1982, Abstract = {The technique of radial unit analysis was applied to the development of the hippocampal region in the mouse. A radial unit was defined as a transect through the neural wall of sufficient size to contain a representative sample of ventricular cells together with their product of neurons. This convention allowed growth to be resolved into two components: a radial component which was a function of the productivity of an individual unit and a tangential component which was a function of the number of participating units. The sequences of cell production, accumulation and dispersal in an average radial unit of the regio superior, regio inferior and dentate gyrus were worked out, and for each area a pattern of summation of such average units into the adult structure was suggested. The approach seemed to offer a useful method for the study of ontogenetic and phylogenetic change in this part of the medical telencephalic wall. 0021-8782 Journal Article}, Author = {Smart, I. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Anat}, Keywords = {Aging;01 Adult neurogenesis general;Cell Differentiation;10 Development;10 Hippocampus;Autoradiography;Time Factors;A,F abstr;Hippocampus/cytology/*embryology/growth &development;Mitosis;Morphogenesis;Animals;Support, Non-U.S. Gov't;Mice;Neurons}, Number = {4}, Pages = {763-93}, Pubmed = {7183676}, Title = {Radial unit analysis of hippocampal histogenesis in the mouse}, Uuid = {D44CCD38-CA84-48B3-B597-1FB3B5414ACF}, Volume = {135}, Year = {1982}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7183676}} @article{Smart:1982a, Abstract = {The distribution of cells of different labelling intensities in the anterior forebrain of adult mice injected with tritiated thymidine at daily intervals during prenatal life was determined by mapping the location of labelled cells on enlarged photographs of autoradiographed sections. The isocortical arc was subdivided into an arbitrary number of radially orientated units. Each radial unit was found to have a similar sequence of arrival and distribution of labelled cells; the ventrolateral units, however, entered and completed the sequence ahead of dorsomedial units indicating the presence of a wave of differentiation spreading in this direction across the generative layers giving rise to cortical neurons. An attempt was made to identify (from differential grain counts) comparable samples of first and second generation cells produced after each pulse of labelled thymidine. The changing ratio between the two generations suggested that there may be two peaks in neuron birth during the generative period. 0021-8782 Journal Article}, Author = {Smart, I. H. and Smart, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Issn = {0021-8782}, Journal = {J Anat}, Keywords = {01 Adult neurogenesis general;Research Support, Non-U.S. Gov't;Telencephalon;Autoradiography;Telencephalon/anatomy &histology/*growth &development;A,F abstr;Animals;Support, Non-U.S. Gov't;Mice}, Medline = {82189660}, Month = {3}, Nlm_Id = {0137162}, Pages = {273-98}, Pubmed = {7076556}, Title = {Growth patterns in the lateral wall of the mouse telencephalon: I. Autoradiographic studies of the histogenesis of the isocortex and adjacent areas}, Uuid = {66D92065-D298-11D9-A0E9-000D9346EC2A}, Volume = {134 (Pt 2)}, Year = {1982}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7076556}} @article{Smetters:1999, Abstract = {The study of neural circuits requires methods for simultaneously recording the activity of populations of neurons. Here, using calcium imaging of neocortical brain slices we take advantage of the ubiquitous distribution of calcium channels in neurons to develop a method to reconstruct the action potentials occurring in a population of neurons. Combining calcium imaging with whole-cell or perforated patch recordings from neurons loaded with acetoxymethyl ester or potassium salt forms of calcium indicators, we demonstrate that each action potential produces a stereotyped calcium transient in the somata of pyramidal neurons. These signals are detectable without averaging, and the signal-to-noise is sufficient to carry out a reconstruction of the spiking pattern of hundreds of neurons, up to relatively high firing frequencies. This technique could in principle be applied systematically to follow the activity of neuronal populations in vitro and in vivo.}, Author = {Smetters, D. and Majewska, A. and Yuste, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1046-2023}, Journal = {Methods}, Keywords = {Fluorescent Dyes;Fura-2;Electrophysiology;Animals;In Vitro;Rats;Rats, Sprague-Dawley;Pyramidal Cells;Calcium;Microscopy, Fluorescence;Time Factors;21 Calcium imaging;Research Support, U.S. Gov't, P.H.S.;Action Potentials;Software;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {99286363}, Month = {6}, Nlm_Id = {9426302}, Number = {2}, Organization = {Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, New York, New York 10027, USA.}, Pages = {215-21}, Pii = {S1046-2023(99)90774-0}, Pubmed = {10356353}, Title = {Detecting action potentials in neuronal populations with calcium imaging}, Uuid = {08FA7E30-7A8E-4C00-A614-A1C8A93ACBE4}, Volume = {18}, Year = {1999}, url = {papers/Smetters_Methods1999.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/meth.1999.0774}} @article{Smith:1998, Abstract = {The anterior portion of the neonatal telencephalic subventricular zone (SVZa) contains proliferating cells that generate an immense number of neurons destined to become the granule and periglomerular cells of the olfactory bulb. In contrast to other immature neurons in the central nervous system, cells arising in the SVZa maintain the ability to divide as they traverse the rostral migratory stream to their final destinations despite expressing an antigenic marker of differentiated neurons (Menezes et al. [1995] Molec. Cell. Neurosci. 6:496-508). Because of their considerable proliferative capacities and unusual mitotic behavior, we decided to determine the cell cycle length of proliferating cells within the SVZa and within the migratory pathway used by SVZa-derived cells. Following the methodology of Nowakowski et al. [1989](J. Neurocytol. 18:311-318), postnatal day 2 rat pups were exposed to 5'-bromo-2'deoxyuridine (BrdU) for increasing periods of time before perfusion. By plotting the percentage of nuclei undergoing DNA synthesis in the SVZa at each time versus the BrdU labeling interval, we determined that approximately 15\%of the SVZa population is actively dividing and that these cells have a cycle length of approximately 14 hr, significantly less than the 18.6 hr determined to be the cycle length of dividing cells in more posterior, glia- generating regions of the subventricular zone (Thomaidou et al. [1997] J. Neurosci. 17:1075-1085). The cycle length of cells dividing in the mid portion of the rostral migratory stream, however, is considerably longer: 17.3 hr. This may reflect the need for these cells to coordinate the processes of migration and division. Our studies also suggest that there may be regional differences in the types of descendants produced by the proliferating cells. Retroviral lineage tracing studies showed that those cells that divide within the rostral migratory stream, like proliferating cells within the SVZa, make cells destined for the olfactory bulb. Unlike the progenitors that divide within the SVZa and generate more granule cells than periglomerular cells, the proliferating cells within the migratory pathway generate more periglomerular cells than granule cells. Collectively the proliferating cells of the SVZa and migratory pathway produce a large number of olfactory bulb interneurons. Our work suggests that this may be achieved in part by the relatively rapid divisions of progenitor cells within the SVZa and in part by the ongoing division of migrating cells en route to the olfactory bulb.}, Author = {Smith, C. M. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Dev Dyn}, Keywords = {Pregnancy;Olfactory Bulb/*cytology/growth &development/metabolism;BB;beta-Galactosidase/genetics/metabolism;Rats;Cell Cycle;Female;Animal;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Interneurons/cytology/metabolism;Cell Movement;Male;Genetic Vectors;Stem Cells/cytology/metabolism;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;Bromodeoxyuridine/metabolism;DNA/biosynthesis;Retroviridae/genetics;Animals, Newborn;Lac Operon;Support, U.S. Gov't, P.H.S.}, Number = {2}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.}, Pages = {220-7.}, Title = {Cell cycle length of olfactory bulb neuronal progenitors in the rostral migratory stream}, Uuid = {8E5676D7-421D-4881-B445-E8D7C3BC22EE}, Volume = {213}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9786422}} @article{Smith:1999, Abstract = {Neuronal heterotopia is a malformation of cortical development that is closely associated with epilepsy in humans. Despite emerging interest in the structure and function of the heterotopic cortex, little is known about the membrane properties and synaptic connections of these displaced neurons. We used whole-cell patch-clamp and extracellular field potential recordings from heterotopic neurons in slices from young adult rats with experimentally induced cortical dysgenesis to determine if local synaptic connections were present in nodular heterotopia. Complex synaptic responses were observed after electrical stimulation of adjacent white matter. The results suggest that neurons in nodular heterotopic gray matter can form local excitatory and inhibitory synaptic connections and may participate in epileptiform events. Copyright Copyright 1999 S. Karger AG, Basel}, Author = {Smith, B. N. and Dudek, F. E. and Roper, S. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Electrophysiology;Animals;Synapses;Rats;Periaqueductal Gray;Synaptic Transmission;Brain;Female;21 Epilepsy;Rats, Sprague-Dawley;21 Dysplasia-heterotopia;Brain Diseases;Bicuculline;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Neurons;24 Pubmed search results 2008;Choristoma}, Medline = {20044660}, Month = {11}, Nlm_Id = {7809375}, Number = {3-5}, Organization = {Department of Anatomy and Neurobiology, Colorado State University College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO, USA.}, Pages = {365-73}, Pii = {dne21365}, Pubmed = {10575260}, Title = {Synaptic responses of neurons in heterotopic gray matter in an animal model of cortical dysgenesis}, Uuid = {51428AA5-1DD1-442E-A086-CDFEF8737718}, Volume = {21}, Year = {1999}, url = {papers/Smith_DevNeurosci1999.pdf}} @article{Smith:2006, Abstract = {Neurogenesis in the adult mammalian hippocampus resulting in long-term persistence of new neurons with features of capacity for functional activation is recognized. Many stimuli are capable of increasing the rate of neurogenesis, including seizure activity. Whether these insults result in an increased number of new functionally active neurons over and above the baseline rate of neurogenesis is not known. The rapid electrical amygdala kindling (REAK) model of seizures isolates the effects of seizures alone in the absence of neuronal death and the resulting seizures induce expression of c-Fos in the vast majority of dentate gyrus (DG) granule cells. C57BL/6 mice were exposed to REAK then injected with bromodeoxyuridine (BrDU) to label dividing cells, then re-exposed to REAK after a delay period to allow detection of functional activation in new neurons by measurement c-Fos expression in response to seizures. Adult subgranular zone cells migrated into the DG granule cell layer (GCL), assumed a neuronal phenotype and demonstrated seizure-dependent responsiveness. Larger absolute numbers of new neurons demonstrating seizure-dependent activation were found in the GCL of previously kindled mice. Seizures are capable of increasing the number of new neurons with the capacity for functional activation laid down in the postseizure period and incorporated into seizure-activated circuitry.}, Author = {Smith, Paul D. and McLean, Karen J. and Murphy, Michael A. and Turnley, Ann M. and Cook, Mark J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8918110}, Number = {11}, Organization = {Centre for Clinical Neurosciences and Neurological Research, St Vincent's Hospital, Melbourne, VIC, Australia 3065.}, Pages = {3195-203}, Pii = {EJN5205}, Pubmed = {17156380}, Title = {Functional dentate gyrus neurogenesis in a rapid kindling seizure model}, Uuid = {FDF65D35-1F27-4DE1-B4FB-B98CDC4CFA4E}, Volume = {24}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.05205.x}} @article{Smith:2001, Abstract = {In visual and somatosensory cortices of several species, spiny stellate cells in layer 4 are the first elements in signal processing where thalamic information is integrated and emergent receptive field properties are generated and sent on to more superficial cortical layers. In vivo and in vitro experiments have provided important information about how the anatomy and physiology of these cells and this layer fit into the functional cortical circuitry. No such data exist for the auditory cortex but are requisite if we are to understand whether ideas about information processing in one sensory cortical area can be generalized to another. Accordingly, we used in vitro slices from which to record and labeled cells in the middle layers of the cat auditory and visual cortices to compare basic anatomical and physiological features of cells recovered in similar layers using the same methods. Our results demonstrate a striking difference in a basic characteristic of two primary sensory cortical areas. In the visual cortex, spiny stellate cells predominate, receive short-latency synaptic inputs, and project to supergranular layers. No such spiny stellate population is encountered in the middle layers of the auditory cortex. Spiny cells that are not stellate or pyramidal are occasionally encountered but, as a group, do not display consistent anatomical or physiological features that might allow them to function as auditory cortical versions of the visual spiny stellates. Rather, pyramidal cells in the lower half of layer 3 and layer 4 appear to have assumed this role.}, Author = {Smith, P. H. and Populin, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Visual Cortex;Auditory Cortex;Electric Stimulation;10 Development;Beta;Cats;Pyramidal Cells;10 Spiny stellate;In Vitro;Support, U.S. Gov't, P.H.S.;10 Structural plasticity;Thalamus;Support, Non-U.S. Gov't;Animals;Neurons;Axons}, Medline = {21340481}, Month = {8}, Nlm_Id = {0406041}, Number = {4}, Organization = {Department of Anatomy, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. smith\@physiology.wisc.edu}, Pages = {508-19}, Pubmed = {11447593}, Title = {Fundamental differences between the thalamocortical recipient layers of the cat auditory and visual cortices}, Uuid = {72385549-B2F0-46AF-BD01-E7F721698DB8}, Volume = {436}, Year = {2001}, url = {papers/Smith_JCompNeurol2001.pdf}} @article{Smith:2004, Abstract = {Viruses replicate within living cells and use the cellular machinery for the synthesis of their genome and other components. To gain access, they have evolved a variety of elegant mechanisms to deliver their genes and accessory proteins into the host cell. Many animal viruses take advantage of endocytic pathways and rely on the cell to guide them through a complex entry and uncoating program. In the dialogue between the cell and the intruder, the cell provides critical cues that allow the virus to undergo molecular transformations that lead to successful internalization, intra-cellular transport, and uncoating.}, Author = {Smith, Alicia E. and Helenius, Ari}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Viral Proteins;Signal Transduction;Animals;review, tutorial;review;15 Retrovirus mechanism;Virion;Carbohydrates;Membrane Microdomains;Active Transport, Cell Nucleus;Membrane Fusion;Cells;Genome, Viral;Cytosol;Viral Physiology;Receptors, Virus;Cell Nucleus;Cell Physiology;Endocytosis;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {0404511}, Number = {5668}, Organization = {Institute of Biochemistry, Swiss Federal Institute of Technology-Zurich, CH-8093 Zurich, Switzerland.}, Pages = {237-42}, Pii = {304/5668/237}, Pubmed = {15073366}, Title = {How viruses enter animal cells}, Uuid = {9D42FF5C-60AF-47C0-B1E5-39CB6735B563}, Volume = {304}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1094823}} @article{Smyth:2002, Abstract = {Seizure activity associated with cortical dysplasia (CD) is often resistant to standard pharmacologic treatments. Although several animal models exhibit CD, virtually nothing is known about antiepileptic drug (AED) responses in these animals. Here we have used rats exposed to methylazoxymethanol acetate (MAM) in utero, an animal model featuring nodular heterotopia, to investigate the effects of AEDs in the dysplastic brain. 4-aminopyridine (100 microM), a K(+) channel blocker, was used to induce interictal epileptiform bursting in acute hippocampal slices from MAM-exposed and age-matched vehicle-injected control animals. Extracellular field recordings were used to monitor seizure activity in vitro. Five commonly used AEDs were tested: phenobarbital, 25-400 microM; carbamazepine, 25-200 microM; valproate (VPA), 0.19-4 mM; ethosuximide (ESM), 0.5-8 mM; and lamotrigine (LTG), 49-390 microM. 4-AP-induced bursting occurred with shorter latencies in slices from MAM-exposed rats in comparison with slices from controls, confirming the intrinsic hyperexcitability of dysplastic tissue. Each AED tested demonstrated significant burst suppression in control slices, but interictal epileptiform bursting in MAM-exposed slices was resistant to these treatments. Even at the highest concentrations, VPA, ESM and LTG had no effect on burst amplitude in slices from MAM-exposed rats. Pharmaco-resistance was further tested by measuring seizure latencies in awake, freely-moving rats after kainate administration (15 mg/kg, i.p.) with and without pre-treatment with VPA (400 mg/kg i.p.). Pre-treatment with VPA prolonged seizure latency in control rats, but had no effect in MAM-exposed animals. These results suggest MAM-exposed rats exhibit a dramatically reduced sensitivity to commonly prescribed AEDs.}, Author = {Smyth, Matthew D. and Barbaro, Nicholas M. and Baraban, Scott C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Anticonvulsants;Pregnancy;Animals;In Vitro;Rats;Phenobarbital;Carbamazepine;Synaptic Transmission;Valproic Acid;Female;Epilepsy;Rats, Sprague-Dawley;Hippocampus;21 Epilepsy;Triazines;Disease Models, Animal;Ethosuximide;Animals, Newborn;Action Potentials;21 Neurophysiology;Methylazoxymethanol Acetate;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;4-Aminopyridine;Electroencephalography;Research Support, Non-U.S. Gov't}, Medline = {22188657}, Month = {8}, Nlm_Id = {8703089}, Number = {3}, Organization = {Department of Neurological Surgery, Epilepsy Research Laboratory, University of California at San Francisco, 94143-0112, USA.}, Pages = {251-64}, Pii = {S0920121102000517}, Pubmed = {12200216}, Title = {Effects of antiepileptic drugs on induced epileptiform activity in a rat model of dysplasia}, Uuid = {7AC84227-3F4B-4F2A-9BF6-F86FF5CE1285}, Volume = {50}, Year = {2002}} @article{Snyder:2002, Abstract = {1078-8956 Comment News}, Author = {Snyder, E. Y. and Park, K. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Nat Med}, Keywords = {06 Adult neurogenesis injury induced;Human;Rats;Radiation Injuries, Experimental/physiopathology;Regeneration/*physiology;Cell Division;Bone Marrow Transplantation;Neuroglia/cytology/physiology/radiation effects;Bromodeoxyuridine/analysis/metabolism;Neuronal Plasticity/*physiology;Neurons/radiation effects;Brain/*physiology/radiation effects;Animals;Cells, Cultured;Stem Cells/*physiology/radiation effects;D pdf;Brain Diseases/*physiopathology}, Number = {9}, Pages = {928-30}, Title = {Limitations in brain repair}, Uuid = {D34149FB-6706-4CA2-9996-C7F917637C19}, Volume = {8}, Year = {2002}, url = {papers/Snyder_NatMed2002.pdf}} @article{Snyder:1997, Abstract = {Neurons undergoing targeted photolytic cell death degenerate by apoptosis. Clonal, multipotent neural precursor cells were transplanted into regions of adult mouse neocortex undergoing selective degeneration of layer II/III pyramidal neurons via targeted photolysis. These precursors integrated into the regions of selective neuronal death; 15 +/- 7\%differentiated into neurons with many characteristics of the degenerated pyramidal neurons. They extended axons and dendrites and established afferent synaptic contacts. In intact and kainic acid- lesioned control adult neocortex, transplanted precursors differentiated exclusively into glia. These results suggest that the microenvironmental alterations produced by this synchronous apoptotic neuronal degeneration in adult neocortex induced multipotent neural precursors to undergo neuronal differentiation which ordinarily occurs only during embryonic corticogenesis. Studying the effects of this defined microenvironmental perturbation on the differentiation of clonal neural precursors may facilitate identification of factors involved in commitment and differentiation during normal development. Because photolytic degeneration simulates some mechanisms underlying apoptotic neurodegenerative diseases, these results also suggest the possibility of neural precursor transplantation as a potential cell replacement or molecular support therapy for some diseases of neocortex, even in the adult.}, Author = {Snyder, E. Y. and Yoon, C. and Flax, J. D. and Macklis, J. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {beta-Galactosidase/biosynthesis;*Nerve Degeneration;Cell Differentiation;Pyramidal Cells/*cytology/physiology;Afferent Pathways;Dendrites/physiology/ultrastructure;Photolysis;Animal;Brain Tissue Transplantation/pathology/*physiology;Mice, Inbred C57BL;Stem Cells/*cytology;Axons/physiology/ultrastructure;*Apoptosis;Support, Non-U.S. Gov't;06 Adult neurogenesis injury induced;Neurons/*cytology/*transplantation/ultrastructure;Support, U.S. Gov't, P.H.S.;Mice;Neocortex/*cytology/*physiology;Genes, Reporter;D-5;Synapses/physiology/ultrastructure}, Number = {21}, Organization = {Department of Neurology, Harvard Medical School, and Division of Neuroscience, Children's Hospital, 320 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {11663-8.}, Title = {Multipotent neural precursors can differentiate toward replacement of neurons undergoing targeted apoptotic degeneration in adult mouse neocortex}, Uuid = {366767C2-EC80-11DA-8605-000D9346EC2A}, Volume = {94}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9326667}} @article{Sockanathan:2003, Abstract = {The identity of motor neurons diverges markedly at different rostrocaudal levels of the spinal cord, but the signals that specify their fate remain poorly defined. We show that retinoid receptor activation in newly generated spinal motor neurons has a crucial role in specifying motor neuron columnar subtypes. Blockade of retinoid receptor signaling in brachial motor neurons inhibits lateral motor column differentiation and converts many of these neurons to thoracic columnar subtypes. Conversely, expression of a constitutively active retinoid receptor derivative impairs the differentiation of thoracic motor neuron columnar subtypes. These findings provide evidence for a regionally restricted role for retinoid signaling in the postmitotic specification of motor neuron columnar identity. 0896-6273 Journal Article}, Author = {Sockanathan, S. and Perlmann, T. and Jessell, T. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Neuron}, Keywords = {Body Patterning/physiology;10 Development;Axons/*metabolism;Neural Pathways/embryology/metabolism;Mitosis/*physiology;Human;F both;Chick Embryo;Gene Expression Regulation, Developmental/physiology;Receptors, Retinoic Acid/*biosynthesis/deficiency/genetics;Embryonic Induction/physiology;Signal Transduction/*physiology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;Motor Neurons/cytology/*metabolism}, Number = {1}, Organization = {Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.}, Pages = {97-111}, Pubmed = {14527436}, Title = {Retinoid receptor signaling in postmitotic motor neurons regulates rostrocaudal positional identity and axonal projection pattern}, Uuid = {5187B76B-95A3-4A77-B94A-80ADFE2FA33F}, Volume = {40}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14527436}} @article{Sohya:2007, Abstract = {Most neurons in the visual cortex are selectively responsive to visual stimulation of a narrow range of orientations, and GABAergic neurons are considered to play a role in the formation of such orientation selectivity. This suggests that response properties of GABAergic neurons may be different from those of excitatory neurons. This view remains unproved, however. To address this issue, we applied in vivo two-photon functional Ca2+ imaging to transgenic mice, in which GABAergic neurons express enhanced green fluorescent protein. Astroglia were stained by an astrocyte-specific dye. The three types of cells, GABAergic neurons, excitatory neurons, and astrocytes, in layer II/III of the visual cortex were differentially identified by using different wavelengths of excitation light and a dichroic mirror for emitted fluorescence, and their responses to moving visual stimuli at different orientations were measured with changes in the intensity of fluorescence of a Ca2+-sensitive dye. We found that almost all GABAergic neurons have orientation-insensitive responses, whereas most of excitatory neurons have orientation-selective responses.}, Author = {Sohya, Kazuhiro and Kameyama, Katsuro and Yanagawa, Yuchio and Obata, Kunihiko and Tsumoto, Tadaharu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;calcium imaging}, Month = {2}, Nlm_Id = {8102140}, Number = {8}, Organization = {Brain Science Institute, RIKEN, Wako 351-0198, Japan.}, Pages = {2145-9}, Pii = {27/8/2145}, Pubmed = {17314309}, Title = {GABAergic neurons are less selective to stimulus orientation than excitatory neurons in layer II/III of visual cortex, as revealed by in vivo functional Ca2+ imaging in transgenic mice}, Uuid = {78F38296-99FB-41DA-86CF-C80E953C3141}, Volume = {27}, Year = {2007}, url = {papers/Sohya_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4641-06.2007}} @article{Solecki:2006, Abstract = {We review studies on the polarity of developing cerebellar granule, showing that the centrosome localizes to the pole of the neuron that extrudes the nascent axon, and the Rho GTPase Cdc42 (cell division cycle 42) activates the mPar6alpha/Par3 (Par for partitioning defective) complex to coordinate actin dynamics in the growth cone. Subsequently, mPar6alpha signaling controls the migration of immature granule neurons down the Bergmann glial fibers into the internal granule cell layer in which they establish synaptic connections.}, Author = {Solecki, David J. and Govek, Eve-Ellen E. and Hatten, Mary E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;24 Pubmed search results 2008;Cell Cycle Proteins;Neuroglia;Membrane Proteins;Cerebellum;Protein Isoforms;research support, n.i.h., extramural;Animals;Cell Movement;Humans;review;Proteins}, Month = {10}, Nlm_Id = {8102140}, Number = {42}, Organization = {Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York 10021, USA.}, Pages = {10624-5}, Pii = {26/42/10624}, Pubmed = {17050699}, Title = {mPar6 alpha controls neuronal migration}, Uuid = {E4CD48E6-AA37-4C1A-8C15-E72DAD9B9CA6}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4060-06.2006}} @article{Solger:2005, Abstract = {PURPOSE: Low-frequency electrical and magnetic stimulation of cortical brain regions has been shown to reduce cortical excitability and to decrease the susceptibility to seizures in humans and in vivo models of epilepsy. The induction of long-term depression (LTD) or depotentiation of a seizure-related long-term potentiation has been proposed to be part of the underlying mechanism. With the low-Mg(2+)-model of epilepsy, this study investigated the effect of electrical LTD, chemical LTD, and depotentiation on the susceptibility of the entorhinal cortex to epileptiform activity. METHODS: The experiments were performed on isolated entorhinal cortex slices obtained from adult Wistar rats and mice. With extracellular recording techniques, we studied whether LTD induced by (a) three episodes of low-frequency paired-pulse stimulation (3 x 900 paired pulses at 1 Hz), and by (b) bath-applied N-methyl-D-aspartate (NMDA, 20 microM) changes time-to-onset, duration, and frequency of seizure-like events (SLEs) induced by omitting MgSO(4) from the artificial cerebrospinal fluid. Next we investigated the consequences of depotentiation on SLEs themselves by applying low-frequency stimulation after onset of low-Mg(2+)-induced epileptiform activity. RESULTS: LTD, induced either by low-frequency stimulation or by bath-applied NMDA, had no effect on time-to-onset, duration, and frequency of SLEs compared with unconditioned slices. Low-frequency stimulation after onset of SLEs did not suppress but induced SLEs that lasted for the time of stimulation and were associated with a simultaneous increase of the extracellular K(+) concentration. CONCLUSIONS: Our study demonstrates that neither conditioning LTD nor brief low-frequency stimulation decreases the susceptibility of the entorhinal cortex to low-Mg(2+)-induced epileptiform activity. The present study does not support the hypothesis that low-frequency brain stimulation exerts its anticonvulsant effect via the induction of LTD or depotentiation.}, Author = {Solger, J{\"o}rg and Heinemann, Uwe and Behr, Joachim}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Long-Term Potentiation;Electric Stimulation Therapy;Electric Stimulation;Animals;In Vitro;Humans;Rats;Seizures;21 Epilepsy;Epilepsy;Entorhinal Cortex;Long-Term Depression (Physiology);Rats, Wistar;Disease Models, Animal;Magnesium Deficiency;N-Methylaspartate;21 Neurophysiology;Mice;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Research Support, Non-U.S. Gov't}, Month = {4}, Nlm_Id = {2983306R}, Number = {4}, Organization = {Neuroscience Research Center of the Charit{\'e}, Humboldt University Berlin, Berlin, Germany.}, Pages = {509-16}, Pii = {EPI41204}, Pubmed = {15816944}, Title = {Electrical and chemical long-term depression do not attenuate low-Mg2+-induced epileptiform activity in the entorhinal cortex}, Uuid = {7C0AA867-9C3B-4A23-922B-D994B735EBD1}, Volume = {46}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.0013-9580.2005.41204.x}} @article{Soloveva:1979, Abstract = {The brains of 7--12 week embryos, developing in normal and mentally ill females (normal--14, schizophrenia--12, other mental disorders--10) were studied by means of electron microscopy. It was established that the cells of the microglia type may be encountered in the brain of embryos beginning from 7 weeks. In the brain of embryos from normal females these cells had mainly a round or oval form (globose microglia). Axons were encountered relatively rarely. Some of the cells had protrusions of the pseudopodia-like type. In the brain of embryos from mentally ill females the cells of the microglia type have diverse, sometimes sticklike forms; they form multiple thin axons, actively fagocyte. The ultrastructure in such conditions was not destructed. These changes are considered to be the result of an increased activity of microglial cells under the influence of factors of the pathological process.}, Author = {Solov'eva, Zh V. h. V. and Orlovskaia, D. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0044-4588}, Journal = {Zh Nevropatol Psikhiatr Im S S Korsakova}, Keywords = {Maternal-Fetal Exchange;Neuroglia;Female;Human;Microscopy, Electron;English Abstract;Not relevant;11 Glia;Pregnancy;Mental Disorders;Schizophrenia;Phagocytosis;Brain}, Medline = {79231744}, Nlm_Id = {8710066}, Number = {7}, Pages = {852-7}, Pubmed = {465151}, Title = {[Microglia-type cells in normal and pathologic human embryonic brains]}, Uuid = {35E732B9-6FBB-4BE1-A2E3-3DB60FE343DF}, Volume = {79}, Year = {1979}} @article{Soltani:2006, Abstract = {Previous studies have shown that non-human primates can generate highly stochastic choice behaviour, especially when this is required during a competitive interaction with another agent. To understand the neural mechanism of such dynamic choice behaviour, we propose a biologically plausible model of decision making endowed with synaptic plasticity that follows a reward-dependent stochastic Hebbian learning rule. This model constitutes a biophysical implementation of reinforcement learning, and it reproduces salient features of behavioural data from an experiment with monkeys playing a matching pennies game. Due to interaction with an opponent and learning dynamics, the model generates quasi-random behaviour robustly in spite of intrinsic biases. Furthermore, non-random choice behaviour can also emerge when the model plays against a non-interactive opponent, as observed in the monkey experiment. Finally, when combined with a meta-learning algorithm, our model accounts for the slow drift in the animal's strategy based on a process of reward maximization.}, Author = {Soltani, Alireza and Lee, Daeyeol and Wang, Xiao-Jing J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0893-6080}, Journal = {Neural Netw}, Keywords = {Stochastic Processes;Animals;Humans;Neural Networks (Computer);Algorithms;20 Networks;comparative study;Probability Learning;09 Evolutionary dynamics;Competitive Behavior;Reaction Time;Choice Behavior;Behavior, Animal;Reinforcement (Psychology);Haplorhini;Neurons;research support, n.i.h., extramural;24 Pubmed search results 2008;Neural Inhibition;Models, Neurological;Likelihood Functions}, Month = {10}, Nlm_Id = {8805018}, Number = {8}, Organization = {Department of Physics and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02454, USA. alireza.soltani\@yale.edu}, Pages = {1075-90}, Pii = {S0893-6080(06)00163-8}, Pubmed = {17015181}, Title = {Neural mechanism for stochastic behaviour during a competitive game}, Uuid = {E801AAF9-20FB-4D1D-8C36-3DB8F7AF1C3E}, Volume = {19}, Year = {2006}, url = {papers/Soltani_NeuralNetw2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neunet.2006.05.044}} @article{Sommer:2002, Abstract = {Normal CNS development involves the sequential differentiation of multipotent stem cells. Alteration of the numbers of stem cells, their self-renewal ability, or their proliferative capacity will have major effects on the appropriate development of the nervous system. In this review, we discuss different mechanisms that regulate neural stem cell differentiation. Proliferation signals and cell cycle regulators may regulate cell kinetics or total number of cell divisions. Loss of trophic support and cytokine receptor activation may differentially contribute to the induction of cell death at specific stages of development. Signaling from differentiated progeny or asymmetric distribution of specific molecules may alter the self-renewal characteristics of stem cells. We conclude that the final decision of a cell to self-renew, differentiate or remain quiescent is dependent on an integration of multiple signaling pathways and at each instant will depend on cell density, metabolic state, ligand availability, type and levels of receptor expression, and downstream cross-talk between distinct signaling pathways. 21896379 0301-0082 Journal Article Review Review, Tutorial}, Author = {Sommer, L. and Rao, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Prog Neurobiol}, Keywords = {B-25;02 Adult neurogenesis migration;Cell Differentiation;Human;Apoptosis;Signal Transduction;Cell Division;Cell Count;Central Nervous System/cytology/*embryology/*growth &development;Animal;Neurons/*cytology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Stem Cells/*cytology}, Number = {1}, Organization = {Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hoenggerberg HPM E38, CH-8093 Zurich, Switzerland. lukas.sommer\@cell.biol.ethz.ch}, Pages = {1-18}, Pubmed = {11897403}, Title = {Neural stem cells and regulation of cell number}, Uuid = {E22C73E3-6FAB-4251-B4AC-D3F679404C7F}, Volume = {66}, Year = {2002}, url = {papers/Sommer_ProgNeurobiol2002}} @article{Song:2004a, Abstract = {Allogeneic stem cell-based transplants may be limited by allograft rejection, as is seen with conventional organ transplantation. One way to avert such a response is to use autologous stem cells, but that may carry the risk of recurrence of the original disease, particularly in the context of a genetic defect. We investigated the potential for gene modification of autologous stem cells to avoid both problems, using recombinant adenoassociated virus vector expressing human alpha1-antitrypsin in murine liver progenitor cells. We showed that recombinant adenoassociated virus 1 was the most efficient vector for liver progenitor cell transduction among five different serotypes of recombinant adenoassociated virus vectors. Ex vivo infected green fluorescent protein-positive liver progenitor cells from C57BL/6 mice with recombinant adenoassociated virus 1-vector-expressing human alpha1 antitrypsin were transplanted into the liver of monocrotaline-treated and partial-hepatectomized C57BL/6 recipients. Using green fluorescent protein as a donor marker, we were able to determine that at 18 weeks after transplantation, approximately 40\%to 50\%of the regenerated liver was green fluorescent protein positive. In addition, transgene expression (serum human alpha1-antitrypsin) was sustained for the length of the study (18 weeks after transplantation). Immunostaining revealed approximately 5\%to 10\%of repopulating liver cells expressing human alpha1-antitrypsin. In conclusion, this study demonstrated the feasibility of long-term engraftment and stability of transgene expression from genetically modified liver progenitor cells with a recombinant adenoassociated virus vector and implies a novel approach to gene therapy for treatment of liver diseases, such as alpha1-antitrypsin deficiency.}, Author = {Song, Sihong and Witek, Rafal P. and Lu, Yuanqing and Choi, Young-Kook K. and Zheng, Donghang and Jorgensen, Marda and Li, Chengwen and Flotte, Terence R. and Petersen, Byron E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0270-9139}, Journal = {Hepatology}, Keywords = {Transgenes;Transduction, Genetic;Animals;Stem Cell Transplantation;Female;Liver;alpha 1-Antitrypsin;Mice, Inbred C57BL;Liver Diseases;alpha 1-Antitrypsin Deficiency;11 Glia;Green Fluorescent Proteins;Research Support, U.S. Gov't, P.H.S.;Hepatectomy;Gene Therapy;Mice;Luminescent Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {8302946}, Number = {4}, Organization = {Department of Pharmaceutics, University of Florida, Gainesville, FL 32610, USA. shsong\@ufl.edu}, Pages = {918-24}, Pubmed = {15382177}, Title = {Ex vivo transduced liver progenitor cells as a platform for gene therapy in mice}, Uuid = {668A72DE-10C8-49FD-8E2A-6C806230C7DC}, Volume = {40}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/hep.20404}} @article{Song:2002a, Abstract = {Neural stem cells are present both in the developing nervous system and in the adult nervous system of all mammals, including humans. Little is known, however, about the extent to which stem cells in adults can give rise to new neurons. We used immunocytochemistry, electron microscopy, fluorescence microscopy (FM imaging) and electrophysiology to demonstrate that progeny of adult rat neural stem cells, when co- cultured with primary neurons and astrocytes from neonatal hippocampus, develop into electrically active neurons and integrate into neuronal networks with functional synaptic transmission. We also found that functional neurogenesis from adult stem cells is possible in co-culture with astrocytes from neonatal and adult hippocampus. These studies show that neural stem cells derived from adult tissues, like those derived from embryonic tissues, retain the potential to differentiate into functional neurons with essential properties of mature CNS neurons.}, Author = {Song, H. J. and Stevens, C. F. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Nat Neurosci}, Keywords = {02 Adult neurogenesis migration;03 Adult neurogenesis progenitor source;BB abstr}, Number = {5}, Organization = {[1] Molecular Neurobiology Laboratory, Howard Hughes Medical Institute at the Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA [2] Laboratory of Genetics, The Salk Institute, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA.}, Pages = {438-445.}, Title = {Neural stem cells from adult hippocampus develop essential properties of functional CNS neurons}, Uuid = {EBAF0E0A-5A02-4BE2-B816-785AEE3D7070}, Volume = {5}, Year = {2002}, url = {papers/Song_NatNeurosci2002.pdf}} @article{Song:2004, Abstract = {The generation of distinct cell types during development depends on the competence of progenitor populations to differentiate along specific lineages. Here we investigate the mechanisms that regulate competence of rodent cortical progenitors to differentiate into astrocytes in response to ciliary neurotrophic factor (CNTF). We found that fibroblast growth factor 2 (FGF2), which by itself does not induce astrocyte-specific gene expression, regulates the ability of CNTF to induce expression of glial fibrillary acidic protein (GFAP). FGF2 facilitates access of the STAT/CBP (signal transducer and activator of transcription/CRE binding protein) complex to the GFAP promoter by inducing Lys4 methylation and suppressing Lys9 methylation of histone H3 at the STAT binding site. Histone methylation at this site is specific to the cell's state of differentiation. In progenitors, the promoter is bound by Lys9-methylated histones, and in astrocytes, it is bound by Lys4-methylated histones, indicating that astrocyte differentiation in vivo involves this switch in chromatin state. Our observations indicate that extracellular signals can regulate access of transcription factors to genomic promoters by local chromatin modification, and thereby regulate developmental competence. 1097-6256 Journal Article}, Author = {Song, M. R. and Ghosh, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Journal = {Nat Neurosci}, Keywords = {04 Adult neurogenesis factors;C, G pdf}, Number = {3}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, 725 N. Wolfe Street, Baltimore, Maryland 21205, USA.}, Pages = {229-35}, Title = {FGF2-induced chromatin remodeling regulates CNTF-mediated gene expression and astrocyte differentiation}, Uuid = {169AD8FB-1C1B-4356-98E0-BFF15C1E97DA}, Volume = {7}, Year = {2004}, url = {papers/Song_NatNeurosci2004.pdf}} @article{Song:2002, Abstract = {During an investigation of the mechanisms through which the local environment controls the fate specification of adult neural stem cells, we discovered that adult astrocytes from hippocampus are capable of regulating neurogenesis by instructing the stem cells to adopt a neuronal fate. This role in fate specification was unexpected because, during development, neurons are generated before most of the astrocytes. Our findings, together with recent reports that astrocytes regulate synapse formation and synaptic transmission, reinforce the emerging view that astrocytes have an active regulatory role--rather than merely supportive roles traditionally assigned to them--in the mature central nervous system. 0028-0836 Journal Article}, Author = {Song, H. and Stevens, C. F. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:39:59 -0400}, Journal = {Nature}, Keywords = {Cell Survival;Animals;Culture Media, Serum-Free;Cells, Cultured;Neurons/*cytology/metabolism;Rats;Hippocampus/cytology/growth &development;Comparative Study;*Cell Differentiation;Stem Cells/*cytology/metabolism;Fibroblasts;Spinal Cord/cytology/growth &development;02 Adult neurogenesis migration;Aging/*physiology;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;BB pdf;Astrocytes/*physiology;Cell Lineage;Organ Specificity;Coculture;Rats, Inbred F344;Laminin/metabolism;Support, U.S. Gov't, P.H.S.;Oligodendroglia/physiology;Cell Division;Animals, Newborn;Bromodeoxyuridine}, Number = {6884}, Organization = {Molecular Neurobiology Laboratory, Howard Hughes Medical Institute at the Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.}, Pages = {39-44}, Title = {Astroglia induce neurogenesis from adult neural stem cells}, Uuid = {82134804-2BA5-47B1-ADD0-8CAE96A4230C}, Volume = {417}, Year = {2002}, url = {papers/Song_Nature2002}} @article{Song:2005, Abstract = {How different is local cortical circuitry from a random network? To answer this question, we probed synaptic connections with several hundred simultaneous quadruple whole-cell recordings from layer 5 pyramidal neurons in the rat visual cortex. Analysis of this dataset revealed several nonrandom features in synaptic connectivity. We confirmed previous reports that bidirectional connections are more common than expected in a random network. We found that several highly clustered three-neuron connectivity patterns are overrepresented, suggesting that connections tend to cluster together. We also analyzed synaptic connection strength as defined by the peak excitatory postsynaptic potential amplitude. We found that the distribution of synaptic connection strength differs significantly from the Poisson distribution and can be fitted by a lognormal distribution. Such a distribution has a heavier tail and implies that synaptic weight is concentrated among few synaptic connections. In addition, the strengths of synaptic connections sharing pre- or postsynaptic neurons are correlated, implying that strong connections are even more clustered than the weak ones. Therefore, the local cortical network structure can be viewed as a skeleton of stronger connections in a sea of weaker ones. Such a skeleton is likely to play an important role in network dynamics and should be investigated further.}, Author = {Song, Sen and Sj{\"o}str{\"o}m, Per Jesper and Reigl, Markus and Nelson, Sacha and Chklovskii, Dmitri B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1545-7885}, Journal = {PLoS Biol}, Keywords = {Synapses;Visual Cortex;research support, non-u.s. gov't;21 Neurophysiology;Cell Communication;Rats;Neuronal Plasticity;Neural Pathways;Signal Transduction;in vitro;research support, n.i.h., extramural;research support, u.s. gov't, p.h.s.;Animals;24 Pubmed search results 2008;Neurons}, Month = {3}, Nlm_Id = {101183755}, Number = {3}, Organization = {Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA.}, Pages = {e68}, Pii = {04-PLBI-RA-0489R2}, Pubmed = {15737062}, Title = {Highly nonrandom features of synaptic connectivity in local cortical circuits}, Uuid = {28EFAA24-5EA5-4B56-87E9-638CB17F3C1E}, Volume = {3}, Year = {2005}, url = {papers/Song_PLoSBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pbio.0030068}} @article{Sorensen:1996, Abstract = {The purpose of the present study was to study if the connectivity of fetal neocortical tissue blocks placed in ischemic brain infarcts of adult rats would be enhanced in rats housed in an enriched environment. We also investigated whether the enriched housing conditions could enhance the postischemic and postgrafting functional outcome, in terms of motor behavior. This part of the study has been published recently. The middle cerebral artery was ligated on the right side in 37 inbred, adult male spontaneously hypertensive rats. The rats were placed at random either in an enriched environment (groups A and B) or in standard laboratory cages (group C). Three weeks after the artery occlusion, blocks of fetal sensorimotor cortex (embryonic day 17) were transplanted into the infarct cavity of rats from groups B and C. After 9 weeks all transplanted rats received an injection, into the graft, of a mixture containing the two tracers Fluoro-Gold and biotinylated Dextran amine. The transplants revealed a structured morphology with whorls and bands of cells reminiscent of normal neocortex. Tracing of efferent transplant to host fibers with biotinylated Dextran amine showed pronounced intrinsic transplant projections, as well as fibers, although significantly fewer, to the host ipsilateral sensorimotor cortex, striatum, and thalamus. Host to transplant projections were revealed by Fluoro-Gold-labeled cells found in the ipsilateral host sensorimotor cortex, the basal nucleus of Meynert, the thalamic ventrobasal, ventrolateral and posterior nuclei, and in the dorsal raphe nuclei. We conclude that fetal frontal neocortical block grafts placed in brain infarcts of adult rats develop a morphology reminiscent of normal neocortex and that both afferent and efferent neural connections, although sparse, are established with the host brain, whether the rats are reared under enriched housing conditions or not. 0014-4886 Journal Article}, Author = {Sorensen, J. C. and Grabowski, M. and Zimmer, J. and Johansson, B. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Exp Neurol}, Keywords = {Fluorescent Dyes;Animals;Neural Pathways/pathology/physiopathology;Rats;Dextrans;*Fetal Tissue Transplantation;Rats, Inbred SHR;Microscopy, Fluorescence;17 Transplant Regeneration;*Stilbamidines;Male;Support, Non-U.S. Gov't;Biotin/analogs &derivatives;L abstr;Brain/pathology/*physiopathology;Cerebral Infarction/pathology/*physiopathology/*surgery;*Brain Tissue Transplantation;Graft Survival}, Number = {2}, Organization = {Department of Neurobiology, Aarhus University, Denmark.}, Pages = {227-35}, Pubmed = {8620921}, Title = {Fetal neocortical tissue blocks implanted in brain infarcts of adult rats interconnect with the host brain}, Uuid = {21025CEF-756A-4B81-A56D-3F2703383E75}, Volume = {138}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8620921}} @article{Soria:2004, Abstract = {The subventricular zone (SVZ) is one of the sources of adult neural stem cells (ANSCs) in the mouse brain. Precursor cells proliferate in the SVZ and migrate through the rostral migratory stream (RMS) to the olfactory bulb (OB), where they differentiate into granule and periglomerular cells. Few transcription factors are known to be responsible for regulating NSC proliferation, migration, and differentiation processes; even fewer have been found to be responsible for the organization of the SVZ and RMS. For this reason, we studied the ventral anterior homeobox (Vax1) gene in NSC proliferation and in SVZ organization. We found that Vax1 is strongly expressed in the SVZ and in the RMS and that, in the absence of Vax1, embryonic precursor cells proliferate 100 times more than wild-type controls, in vitro. The SVZ of Vax1(-/-) brains is hyperplastic and mostly disorganized, and the RMS is missing, causing a failure of precursor cell migration to the OBs, which as a result are severely hypoplastic. Moreover, we found that Vax1 is essential for the correct differentiation of ependyma and astrocytes. Together, these data indicate that Vax1 is a potent regulator of SVZ organization and NSC proliferation, with important consequences on postnatal neurogenesis.}, Author = {Soria, Jos{\'e} Miguel and Taglialatela, Paola and Gil-Perotin, Sara and Galli, Rossella and Gritti, Angela and Verdugo, Jos{\'e} Manuel Garcia and Bertuzzi, Stefano}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Month = {12}, Nlm_Id = {8102140}, Number = {49}, Organization = {Dulbecco Telethon Institute at Consiglio Nazionale delle Ricerche-Istituto di Tecnologie Biomediche, 20090 Segrate, Milan, Italy.}, Pages = {11171-81}, Pii = {24/49/11171}, Pubmed = {15590934}, Title = {Defective postnatal neurogenesis and disorganization of the rostral migratory stream in absence of the Vax1 homeobox gene}, Uuid = {AD8B1B66-A3E5-11DA-AB00-000D9346EC2A}, Volume = {24}, Year = {2004}, url = {papers/Soria_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3248-04.2004}} @article{Soriano:2005, Abstract = {Cajal-Retzius (CR) cells are an enigmatic class of neurons located at the surface of the cerebral cortex, playing a major role in cortical development. In this review, we discuss several distinct features of these neurons and the mechanisms by which they regulate cortical development. Many CR cells likely have extracortical origin and undergo cell death during development. Recent genetic studies report unique patterns of gene expression in CR cells, which may help to explain the developmental processes in which they participate. Moreover, a number of studies indicate that CR cells, and their secreted gene product, reelin, are involved in neuronal migration by acting on two key partners, migrating neurons and radial glial cells. Emerging data show that these neurons are a critical part of an early and complex network of neural activity in layer I, supporting the notion that CR cells modulate cortical maturation. Given these key and complex developmental properties, it is therefore conceivable for CR cells to be implicated in the pathogenesis of a variety of neurological disorders.}, Author = {Soriano, Eduardo and Del R{\'\i}o, Jos{\'e} Antonio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Institut de Recerca Biomedica de Barcelona, Parc Cientific de Barcelona, University of Barcelona, Barcelona 08028, Spain. esoriano\@pcb.ub.es}, Pages = {389-94}, Pii = {S0896-6273(05)00355-7}, Pubmed = {15882637}, Title = {The cells of cajal-retzius: still a mystery one century after}, Uuid = {E4CBE92F-D225-49BD-9D69-9F6224D097A6}, Volume = {46}, Year = {2005}, url = {papers/Soriano_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.019}} @article{Soriano:1995, Abstract = {We have analyzed the developmental pattern of beta-galactosidase (beta-gal) expression in the cerebral cortex of the beta 2nZ3'1 transgenic mouse line, which was generated using regulatory elements of the beta 2-microglobulin gene and shows ectopic expression in nervous tissue. From embryonic day 10 onward, beta-gal was expressed in the medial and dorsal cortices, including the hippocampal region, whereas lateral cortical areas were devoid of labeling. During the period of cortical neurogenesis (embryonic days 11-17), beta-gal was expressed by selective precursors in the proliferative ventricular zone of the neocortex and hippocampus, as well as by a number of migrating and postmigratory neurons arranged into narrow radial stripes above the labeled progenitors. Thus, the transgene labels a subset of cortical progenitors and their progeny. Postnatally, radial clusters of beta-gal-positive neurons were discernible until postpartum day 10. At this age, the clusters were 250 to 500 microns wide, composed of neurons spanning all the cortical layers and exhibiting several neuronal phenotypes. These data suggest molecular heterogeneity of cortical progenitors and of the cohorts of postmitotic neurons originating from them, which implies intrinsic molecular mosaicism in both cortical progenitors and developing neurons. Furthermore, the data show that neurons committed to the expression of the transgene migrate along very narrow, radial stripes.}, Author = {Soriano, E. and Dumesnil, N. and Auladell, C. and Cohen-Tannoudji, M. and Sotelo, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {10 Development;beta-Galactosidase;Animals;Phenotype;Mitosis;Cell Movement;Mice, Transgenic;Staining and Labeling;research support, non-u.s. gov't;Cerebral Cortex;Neurons;Lac Operon;Genetic Heterogeneity;Mice;Genes, Reporter;Immunohistochemistry;Stem Cells;24 Pubmed search results 2008;beta 2-Microglobulin}, Month = {12}, Nlm_Id = {7505876}, Number = {25}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale, Unit{\'e} 106 H\^{o}pital de la Salp\^{e}tri\`{e}re, Paris, France.}, Pages = {11676-80}, Pubmed = {8524827}, Title = {Molecular heterogeneity of progenitors and radial migration in the developing cerebral cortex revealed by transgene expression}, Uuid = {8D76EF95-10D8-4CB8-AD2D-F4EEF8FAB680}, Volume = {92}, Year = {1995}, url = {papers/Soriano_ProcNatlAcadSciUSA1995.pdf}} @article{Sossey-Alaoui:1998, Abstract = {Subcortical band heterotopia (SBH) and classical lissencephaly (LIS) result from deficient neuronal migration which causes mental retardation and epilepsy. A single LIS/SBH locus on Xq22.3-q24 was mapped by linkage analysis and physical mapping of the breakpoint in an X;2 translocation. A recently identified gene, doublecortin ( DCX ), is expressed in fetal brain and mutated in LIS/SBH patients. We have identified four novel missense mutations in the gene, one familial mutation with LIS in a male and SBH in the carrier females, one de novo mutation in an SBH female, and two mutations in sporadic SBH female patients. The DCX gene is found to be expressed exclusively at a very high level in the adult frontal lobe. We have also cloned the X-linked mouse doublecortin (Dcx) gene. It encodes isoforms of a highly hydrophilic 40 kDa protein, homologous to its human counterpart and containing several potential phosphorylation sites. Both human and mouse DCX proteins are homologous to a CNS protein containing a Ca2+/calmodulin kinase domain, suggesting that the DCX protein may belong to a novel class of intracellular proteins involved in neuronal migration through Ca2+-dependent signaling.}, Author = {Sossey-Alaoui, K. and Hartung, A. J. and Guerrini, R. and Manchester, D. K. and Posar, A. and Puche-Mira, A. and Andermann, E. and Dobyns, W. B. and Srivastava, A. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0964-6906}, Journal = {Hum Mol Genet}, Keywords = {10 Development;Signal Transduction;Animals;Microtubule-Associated Proteins;Humans;Sequence Homology, Amino Acid;Female;Epilepsy;Cell Movement;Mental Retardation;Calcium;Male;Neuropeptides;Linkage (Genetics);Research Support, U.S. Gov't, P.H.S.;X Chromosome;Neurons;Adult;Mice;Amino Acid Sequence;Molecular Sequence Data}, Medline = {98334553}, Month = {8}, Nlm_Id = {9208958}, Number = {8}, Organization = {J. C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC 29646, USA.}, Pages = {1327-32}, Pii = {ddb156}, Pubmed = {9668176}, Title = {Human doublecortin (DCX) and the homologous gene in mouse encode a putative Ca2+-dependent signaling protein which is mutated in human X-linked neuronal migration defects}, Uuid = {C9480CCC-F0DE-400C-98C8-3794697DCC1A}, Volume = {7}, Year = {1998}, url = {papers/Sossey-Alaoui_HumMolGenet1998.pdf}} @article{Sotelo:1991, Abstract = {Repair of adult 'point-to-point'systems by neural grafting is possible only when grafted neurons succeed in synaptically replacing the host's missing neurons, thus re-establishing the anatomical and functional integrity of the impaired circuits. Grafting experiments carried out on the cerebellum of the adult pcd (Purkinje-cell-degeneration) mutant mouse (an animal model of hereditary degenerative ataxia) reveal that embryonic Purkinje cells, by some unknown sorting mechanism, selectively invade the deprived cerebellar cortex. These neurons migrate to their proper domains and, inducing axonal sprouting of specific populations of host neurons, they become integrated synaptically within the pcd cerebellar cortex. However, the re-establishment of the corticonuclear projection is achieved only rarely, and this is the current experimental limit for the complete reconstruction of the cerebellar circuit. 0166-2236 Journal Article Review Review, Tutorial}, Author = {Sotelo, C. and Alvarado-Mallart, R. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Trends Neurosci}, Keywords = {Mice;Nerve Degeneration/physiology;Purkinje Cells/physiology/transplantation;17 Transplant Regeneration;Human;Dendrites/physiology;L abstr;Support, Non-U.S. Gov't;Animals;Cerebellum/*surgery/transplantation;Mice, Neurologic Mutants;Brain Tissue Transplantation/physiology}, Number = {8}, Organization = {Laboratory of Neuromorphology, INSERM U 106, Hopital de la Salpetriere, France.}, Pages = {350-5}, Pubmed = {1721740}, Title = {The reconstruction of cerebellar circuits}, Uuid = {9B1EF6E8-3226-4877-9496-443FF742F309}, Volume = {14}, Year = {1991}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1721740}} @article{Spalding:1998, Abstract = {In neonatal rats, intraocular injections of brain-derived neurotrophic factor (BDNF) or neurotrophin 4/5 (NT-4/5) enhance the survival of retinal ganglion cells (RGCs) following superior colliculus (SC) ablation [Q. Cui, A.R. Harvey, At least two mechanisms are involved in the death of retinal ganglion cells following target ablation in neonatal rats, J. Neurosci., 15, 1995, pp. 8143-8155.]. The aim of the present study was to determine if: (i) fetal tectal tissue grafted into the lesion site, or (ii) neurotrophins applied centrally to the injured SC, also decreased lesion-induced RGC death. Nuclei of tectally projecting RGCs were identified by injecting diamidino yellow (DY) into the left SC of 2-day-old (P2) Wistar rats. Injected SCs were lesioned at P4. In some animals, embryonic (E16) tectal tissue was then implanted into the lesion cavity; host rats were perfused 24 h or 20 days later. In short-term (24-h) studies, the number of DY-labelled pyknotic profiles was compared to the number of normal DY-labelled RGCs in retinal wholemounts (right eyes). The proportion of dying RGCs in animals with grafts (10.7\%, n = 17) was not significantly different from lesion-only rats (13.2\%, n = 26). Nonetheless, the long-term (20-day) study showed that, in most rats, fetal tectal tissue survived in the lesion cavity and in some cases, the grafts received host retinal input. In another group, different doses of BDNF or NT-4/5 were applied to the SC after P4 tectal lesions. Rats were perfused 24 h later and the number of pyknotic vs. normal DY-labelled RGCs was determined. Initial trials in which SC lesions were filled with gelfoam soaked in BDNF or NT-4/5 were unsuccessful; however, RGC death was reduced (p < 0.05, Dunnett's test) in rats that received gelfoam implants as well as focal neurotrophin injections into SC rostral to the lesion. The lowest pyknotic rate in individual animals from the BDNF and NT-4/5 groups was 2.41\%and 2.01\%, respectively. Overall, the proportion of dying RGCs was 7.0\%(n = 8) for BDNF and 7.4\%(n = 17) for NT-4/5 treated rats. Normal RGC densities were also significantly higher in these animals. NT-4/5 topically applied to the posterior surface of the eye did not reduce RGC death. The data show that the viability of injured neonatal RGCs is increased by specific retrograde neurotrophin-mediated survival signals which can be activated from the SC.}, Author = {Spalding, K. L. and Cui, Q. and Harvey, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0165-3806}, Journal = {Brain Res Dev Brain Res}, Keywords = {Superior Colliculus;Ophthalmic Solutions;Research Support, Non-U.S. Gov't;Rats;Administration, Topical;Rats, Wistar;Cell Survival;Animals, Newborn;Brain-Derived Neurotrophic Factor;Retinal Ganglion Cells;Animals;24 Pubmed search results 2008;Nerve Growth Factors;Fetal Tissue Transplantation}, Medline = {98270046}, Month = {4}, Nlm_Id = {8908639}, Number = {1}, Organization = {Department of Anatomy and Human Biology, University of Western Australia, Nedlands, Perth, Australia.}, Pages = {133-42}, Pii = {S0165380698000108}, Pubmed = {9602096}, Title = {The effects of central administration of neurotrophins or transplants of fetal tectal tissue on retinal ganglion cell survival following removal of the superior colliculus in neonatal rats}, Uuid = {BFEDD079-7532-4EA9-A9B9-DA3A22563EE5}, Volume = {107}, Year = {1998}} @article{Spalding:2005, Abstract = {The generation of cells in the human body has been difficult to study, and our understanding of cell turnover is limited. Testing of nuclear weapons resulted in a dramatic global increase in the levels of the isotope 14C in the atmosphere, followed by an exponential decrease after 1963. We show that the level of 14C in genomic DNA closely parallels atmospheric levels and can be used to establish the time point when the DNA was synthesized and cells were born. We use this strategy to determine the age of cells in the cortex of the adult human brain and show that whereas nonneuronal cells are exchanged, occipital neurons are as old as the individual, supporting the view that postnatal neurogenesis does not take place in this region. Retrospective birth dating is a generally applicable strategy that can be used to measure cell turnover in man under physiological and pathological conditions.}, Author = {Spalding, Kirsty L. and Bhardwaj, Ratan D. and Buchholz, Bruce A. and Druid, Henrik and Fris{\'e}n, Jonas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Cell Aging;Humans;Aging;Air Pollutants, Radioactive;DNA;Research Support, U.S. Gov't, Non-P.H.S.;Male;Nuclear Warfare;01 Adult neurogenesis general;Research Support, U.S. Gov't, P.H.S.;Time;Carbon Radioisotopes;Cerebral Cortex;Neurons;Retrospective Studies;Adult;Cell Nucleus;Pinus;Organ Specificity;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't}, Month = {7}, Nlm_Id = {0413066}, Number = {1}, Organization = {Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institute, SE-171 77 Stockholm, Sweden.}, Pages = {133-43}, Pii = {S0092-8674(05)00408-3}, Pubmed = {16009139}, Title = {Retrospective birth dating of cells in humans}, Uuid = {258ABF40-A759-11DA-AF0C-000D9346EC2A}, Volume = {122}, Year = {2005}, url = {papers/Spalding_Cell2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.04.028}} @article{Spassky:2005, Abstract = {Ependymal cells on the walls of brain ventricles play essential roles in the transport of CSF and in brain homeostasis. It has been suggested that ependymal cells also function as stem cells. However, the proliferative capacity of mature ependymal cells remains controversial, and the developmental origin of these cells is not known. Using confocal or electron microscopy (EM) of adult mice that received bromodeoxyuridine (BrdU) or [3H]thymidine for several weeks, we found no evidence that ependymal cells proliferate. In contrast, ependymal cells were labeled by BrdU administration during embryonic development. The majority of them are born between embryonic day 14 (E14) and E16. Interestingly, we found that the maturation of ependymal cells and the formation of cilia occur significantly later, during the first postnatal week. We analyzed the early postnatal ventricular zone at the EM and found a subpopulation of radial glia in various stages of transformation into ependymal cells. These cells often had deuterosomes. To directly test whether radial glia give rise to ependymal cells, we used a Cre-lox recombination strategy to genetically tag radial glia in the neonatal brain and follow their progeny. We found that some radial glia in the lateral ventricular wall transform to give rise to mature ependymal cells. This work identifies the time of birth and early stages in the maturation of ependymal cells and demonstrates that these cells are derived from radial glia. Our results indicate that ependymal cells are born in the embryonic and early postnatal brain and that they do not divide after differentiation. The postmitotic nature of ependymal cells strongly suggests that these cells do not function as neural stem cells in the adult.}, Author = {Spassky, Nathalie and Merkle, Florian T. and Flames, Nuria and Tramontin, Anthony D. and Garc{\'\i}a-Verdugo, Jos{\'e} Manuel and Alvarez-Buylla, Arturo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Department of Neurological Surgery and Program in Developmental and Stem Cell Biology, University of California San Francisco, San Francisco, California 94143, USA.}, Pages = {10-8}, Pii = {25/1/10}, Pubmed = {15634762}, Title = {Adult ependymal cells are postmitotic and are derived from radial glial cells during embryogenesis}, Uuid = {FBA68663-053C-4DA7-ADEA-96E594E7F24D}, Volume = {25}, Year = {2005}, url = {papers/Spassky_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1108-04.2005}} @article{Spiegel:2006, Abstract = {The formation of the myelin sheath in the CNS is the endpoint of a defined developmental program along which oligodendrocytes progress. However, the molecular signals required for the initiation of myelination are largely unknown. Ishibashi et al. report in this issue of Neuron that ATP released by axons as a result of electrical stimulation serves as an important myelination signal. Surprisingly, they found that ATP does not act directly on oligodendrocytes but rather on astrocytes, causing the release of leukemia inhibitory factor (LIF), which in turns affects promyelinating oligodendrocytes. These findings uncover a novel role for astrocytes in mediating the intricate communication between axons and myelinating glial cells.}, Author = {Spiegel, Ivo and Peles, Elior}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {comment;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel.}, Pages = {777-8}, Pii = {S0896-6273(06)00167-X}, Pubmed = {16543121}, Title = {A new player in CNS myelination}, Uuid = {6FD68E86-F5BA-44F2-97D5-DFC12E0DB100}, Volume = {49}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.03.001}} @article{Spors:2002, Abstract = {We explored the spatio-temporal dynamics of odor-evoked activity in the rat and mouse main olfactory bulb (MOB) using voltage-sensitive dye imaging (VSDI) with a new probe. The high temporal resolution of VSDI revealed odor-specific sequences of glomerular activation. Increasing odor concentrations reduced response latencies, increased response amplitudes, and recruited new glomerular units. However, the sequence of glomerular activation was maintained. Furthermore, we found distributed MOB activity locked to the nasal respiration cycle. The spatial distribution of its amplitude and phase was heterogeneous and changed by sensory input in an odor-specific manner. Our data show that in the mammalian olfactory bulb, odor identity and concentration are represented by spatio-temporal patterns, rather than spatial patterns alone.}, Author = {Spors, H. and Grinvald, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Neuron}, Keywords = {I abstr;13 Olfactory bulb anatomy; in vivo; optical physiology; optical imaging; voltage sensor; Dyes; Fluorescence; sensory map; topographic map; function; mouse; mice; Rats}, Number = {2}, Organization = {The Department of Neurobiology, Weizmann Institute of Science, 76100, Rehovot, Israel}, Pages = {301-15.}, Title = {Spatio-temporal dynamics of odor representations in the Mammalian olfactory bulb}, Uuid = {2CB03EAF-58AC-4D46-B4BC-4C393D1D68E3}, Volume = {34}, Year = {2002}, url = {papers/Spors_Neuron2002.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11970871}} @article{Spradling:2001, Abstract = {The concept that stem cells are controlled by particular microenvironments known as 'niches'has been widely invoked. But niches have remained largely a theoretical construct because of the difficulty of identifying and manipulating individual stem cells and their surroundings. Technical advances now make it possible to characterize small zones that maintain and control stem cell activity in several organs, including gonads, skin and gut. These studies are beginning to unify our understanding of stem cell regulation at the cellular and molecular levels, and promise to advance efforts to use stem cells therapeutically. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Spradling, A. and Drummond-Barbosa, D. and Kai, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Nature}, Keywords = {Testis/cytology;F abstr;10 Development;Intestines/cytology;Ovary/cytology;Female;Hematopoietic Stem Cells/cytology;Mammals;Epithelial Cells;*Stem Cells;Caenorhabditis elegans/cytology;Endoderm/cytology;Drosophila/cytology;Skin/cytology;Animals;Male}, Number = {6859}, Organization = {HHMI/Department of Embryology, Carnegie Institution of Washington, Baltimore, Maryland 21210, USA.}, Pages = {98-104}, Pubmed = {11689954}, Title = {Stem cells find their niche}, Uuid = {82B836D0-B729-4ADA-A323-073B5D18A71F}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689954}} @article{Spreafico:2000, Abstract = {PURPOSE: Different types of epilepsies and seizures depend on the nature and location of the primary disturbance and are presumably mediated by different physiopathological mechanisms. We immunocytochemically investigated possible changes in the inhibitory-aminobutyric acid (GABA)ergic system in specimens taken from four patients who underwent surgery for intractable epilepsy and presented two different types of focal cortical dysplasia in the temporal lobe. METHODS: The patients were selected on the basis of electroclinical, imaging, and routine neuropathological data: two had Taylor focal dysplasia, and two had non-Taylor dysplasia (microdysgenesia). The study was performed using antibodies against parvalbumin (PV), glutamic acid decarboxylase (GAD), and GABA-transporter 1 (GAT1). RESULTS: In the patients with Taylor dysplasia, laminar disorganization of the cortex was associated with the presence of giant neurons and ballooned cells; there was a reduced number of PV-positive neurons and terminals, the giant neurons were surrounded by clusters of PV- and GAD-positive terminals, and there was an overall reduction in GAT1. Despite the presence of cortical laminar disorganization, no giant or ballooned cells were found in the patients with non-Taylor microdysgenesia; there was a marked decrease in PV and GAD immunoreactive elements, with a patchy distribution of GAD and GAT1 immunoreactivity but no clustering of PV and GAD terminals. CONCLUSIONS: These results suggest that the two forms of cortical dysplasia are characterized by different and selective morphofunctional alterations in the GABAergic system.}, Author = {Spreafico, R. and Tassi, L. and Colombo, N. and Bramerio, M. and Galli, C. and Garbelli, R. and Ferrario, A. and Lo Russo, G. and Munari, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:57 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {24 Pubmed search results 2008;10 Development;research support, non-u.s. gov't;Adult;Magnetic Resonance Imaging;Epilepsy, Temporal Lobe;Female;Immunohistochemistry;Neural Pathways;Neural Inhibition;10 genetics malformation;gamma-Aminobutyric Acid;Humans;Male;Cerebral Cortex;Neurons;Temporal Lobe}, Nlm_Id = {2983306R}, Organization = {Divisione di Neurofisiologia Sperimentale ed Epilettologia, Istituto Nazionale Neurologico C. Besta, Milan, Italy. spreafico\@istituto-besta.it}, Pages = {S168-73}, Pubmed = {10999539}, Title = {Inhibitory circuits in human dysplastic tissue}, Uuid = {06513A9F-B260-47D3-9F7B-51BAACE53E8A}, Volume = {41 Suppl 6}, Year = {2000}, url = {papers/Spreafico_Epilepsia2000.pdf}} @article{Spreafico:1998, Abstract = {In this report we describe three patients with developmental cortical abnormalities (generally referred as cortical dysplasia), revealed by MRI and operated on for intractable epilepsy. Tissue, removed for strictly therapeutic reasons, was defined as the epileptogenic area by electroclinical data and stereo EEG (SEEG) recordings. Tissue samples were processed initially for histology, and selected sections were further processed for immunocytochemical investigation in order to determine whether the region of cortical dysplasia was co-extensive with the epileptogenic area. In two patients with nodular heterotopia, disorganized aggregates of neurons (as revealed by neuronal cytoskeletal markers) were found within the nodules. Both pyramidal and local circuit neurons were present in the nodules, but no reactive gliosis was present. When nodules reached the cortex, the cortical layers were disrupted. In the patient with localized cortical dysplasia, a complete disorganization of the cortical lamination was found, and numerous neurons were also present in the white matter. Disoriented pyramidal neurons weakly labelled with cytoskeletal neuronal markers were also present but no cytomegalic cells were found. One of the patients with nodular heterotopia underwent only partial resection of both the 'epileptogenic area' and of the lesion; this patient still presents with seizures. The other patient with nodular heterotopia is seizure-free after a complete lesionectomy and excision of the epileptogenic area. The third patient, with focal cortical dysplasia, had two surgeries; she became seizure-free only after the excision of the epileptogenic area detected by SEEG recording. The present data suggest that the dysplastic areas identified by MRI should not be considered as the only place of origin of the ictal discharges. From the neuropathological point of view, the focal cortical dysplasia can be considered as a pure form of migrational disorder. However, the presence of large aggregates of neurons interspersed within the white matter, in the subcortical nodular heterotopia, suggests that a defect of neuronal migration could be associated with an exuberant production of neuroblasts and/or a disruption of mechanisms for naturally occurring cell death.}, Author = {Spreafico, R. and Pasquier, B. and Minotti, L. and Garbelli, R. and Kahane, P. and Grand, S. and Benabid, A. L. and Tassi, L. and Avanzini, G. and Battaglia, G. and Munari, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:45:57 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {21 Epilepsy;Epilepsies, Partial;Electroencephalography;10 Development;Magnetic Resonance Imaging;21 Neurophysiology;Research Support, Non-U.S. Gov't;Immunohistochemistry;Pyramidal Cells;Choristoma;10 genetics malformation;Humans;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Medline = {98432474}, Month = {9}, Nlm_Id = {8703089}, Number = {1-2}, Organization = {Department of Neurophysiology, National Neurological Institute C. Besta, Milano, Italy. spreafico.besta\@interbusiness.it}, Pages = {34-48}, Pii = {S0920-1211(98)00038-2}, Pubmed = {9761307}, Title = {Immunocytochemical investigation on dysplastic human tissue from epileptic patients}, Uuid = {15ACA67F-5970-4AAC-83A8-BF4A05110B25}, Volume = {32}, Year = {1998}, url = {papers/Spreafico_EpilepsyRes1998.pdf}} @article{Spreafico:1998a, Abstract = {Human cortical dysplastic lesions are frequently associated with severe partial epilepsies. We report an immunocytochemical investigation on cortical tissue from three surgically treated patients, 20, 38, and 14 years old, with intractable epilepsy due to cortical dysplasia. The studies were performed using antibodies recognizing cytoskeletal proteins, calcium-binding proteins, and some subunits of glutamate receptors. The specimens from the three patients displayed common features: (1) focal cytoarchitectural abnormalities with an increased number of giant pyramidal neurons through all cortical layers except layer I; (2) large, round-shaped balloon cells mainly concentrated in the deepest part of the cortex and in the white matter; (3) a decrease of calcium binding protein immunopositive gamma-aminobutyric acid (GABA)ergic neurons; and (4) abnormal baskets of parvalbumin-positive terminals around the excitatory (pyramidal and large, round-shaped) neurons. These data provide evidence that the epileptogenicity in these types of cortical dysplasia is due to an increase in excitatory neurons coupled with a decrease in GABAergic interneurons.}, Author = {Spreafico, R. and Battaglia, G. and Arcelli, P. and Andermann, F. and Dubeau, F. and Palmini, A. and Olivier, A. and Villemure, J. G. and Tampieri, D. and Avanzini, G. and Avoli, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0028-3878}, Journal = {Neurology}, Keywords = {gamma-Aminobutyric Acid;10 Development;Microtubule-Associated Proteins;Magnetic Resonance Imaging;Epilepsies, Partial;Humans;Female;Pyramidal Cells;research support, non-u.s. gov't;Calcium-Binding Protein, Vitamin D-Dependent;Male;Brain Chemistry;10 genetics malformation;Parvalbumins;Cerebral Cortex;Adult;Interneurons;Immunohistochemistry;24 Pubmed search results 2008;Nerve Tissue Proteins;Adolescent}, Month = {1}, Nlm_Id = {0401060}, Number = {1}, Organization = {Istituto Nazionale Neurologico C. Besta, Department of Experimental Neurophysiology and Epileptology, Milano, Italy.}, Pages = {27-36}, Pubmed = {9443453}, Title = {Cortical dysplasia: an immunocytochemical study of three patients}, Uuid = {689B915F-B147-4E99-97E4-D2FF5320B1AF}, Volume = {50}, Year = {1998}} @article{Staber:1978, Author = {Staber, F. G. and Schl{\"a}fli, E. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {15 ERVs retroelements;Cell Differentiation;Hematopoietic Stem Cells;Retroviridae;Antigens, Surface;15 Retrovirus mechanism;Animals;Spleen;Mice;Antigens, Viral;24 Pubmed search results 2008}, Medline = {79032157}, Month = {10}, Nlm_Id = {0410462}, Number = {5681}, Pages = {669-71}, Pubmed = {212682}, Title = {Expression of endogenous C-type viral antigen on normal mouse haemopoietic stem cells}, Uuid = {86028F6A-8C08-4E8C-94A2-5F619E39A0EA}, Volume = {275}, Year = {1978}} @article{Stables:2002, Abstract = {PURPOSE: The workshop explored the current problems, needs, and potential usefulness of existing methods of discovery of new therapies to treat epilepsy patients. Resistance to medical therapy (pharmacoresistance) and the development of epilepsy (epileptogenesis) are recognized as two of the major problems in epilepsy treatment today. At the same time, there is growing awareness that the development of new therapies has slowed, a trend that has economic and scientific roots. To move toward new and more effective therapies, novel approaches to therapy discovery are needed. METHODS: A workshop was held in March 2001 with the charge to develop a plan to move the exploration and discovery process forward. Participants from academia, government, and industry reviewed the current status of epilepsy therapy and explored the identification of potential new therapies. RESULTS: At the end of the 2-day meeting, the panel made a series of recommendations. The two major recommendations were (a) to establish a means for continuing the examination of new approaches to therapy discovery, and (b) to identify models and approaches to therapy discovery that may identify treatments that are more successful than those available. Further recommendations were made to support the development of technology (miniaturization, computerization, video monitoring, etc.) to facilitate the use of the new models and to identify the mechanisms of therapy success and failure. CONCLUSIONS: Understanding the epidemiology of therapy resistance and providing support for new approaches to therapy development were identified as key issues for introduction of new and more effective treatments.}, Author = {Stables, James P. and Bertram, Edward H. and White, H. Steve and Coulter, Douglas A. and Dichter, Marc A. and Jacobs, Margaret P. and Loscher, Wolfgang and Lowenstein, Daniel H. and Moshe, Solomon L. and Noebels, Jeffrey L. and Davis, Mirian}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Epilepsy;Technology, Pharmaceutical;24 Pubmed search results 2008;21 Epilepsy;Anticonvulsants;21 Neurophysiology;consensus development conference;Child, Preschool;Drug Resistance;Humans;Animals;Disease Models, Animal;review;consensus development conference, nih}, Medline = {22310892}, Month = {11}, Nlm_Id = {2983306R}, Number = {11}, Organization = {National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA. stablesj\@ninds.nih.gov}, Pages = {1410-20}, Pii = {epi06702}, Pubmed = {12423393}, Title = {Models for epilepsy and epileptogenesis: report from the NIH workshop, Bethesda, Maryland}, Uuid = {6259E419-9A1B-459F-8E40-A364535106BE}, Volume = {43}, Year = {2002}} @article{Stagaard:1987, Abstract = {The population of microglial cells in the subependymal layer of the subcommissural organ is sparse in normal adult rats. The number of microglial cells was substantially increased in this area following intraventricular injection of the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT). In sections of plastic embedded material, 1 micron thick, the majority of phagocytic cells scattered in the subependymal layer had an appearance similar to that described in classical studies of microglial cells. At the electron microscopic level microglial cells exhibited the characteristic elongate nucleus with peripheral chromatin condensation. The perikaryon was scanty, containing strands of rough endoplasmic reticulum. The abundant organelles in the processes included Golgi complexes, mitochondria, rough and smooth endoplasmic reticulum as well as dense and multivesicular bodies. In addition, the processes contained phagocytosed axon terminals originating from the dense serotoninergic input to the subcommissural organ, which had degenerated on accumulating the serotonin neurotoxin. A fraction of the phagocytosed material was contained in subependymal subcommissural organ cells, astrocytes and oligodendrocytes. At the light microscopic level the phagocytosed terminals were visualized histochemically with Schmorl's reaction, which resulted in Prussian Blue precipitates. This allowed screening of microglial cells in complete series of sections through the well-defined subependymal layer of the subcommissural organ.}, Author = {Stagaard, M. and Balslev, Y. and Lundberg, J. J. and M\ollg\r{a}rd, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Brain Diseases;Neuroglia;5,6-Dihydroxytryptamine;Rats;Microscopy, Electron;Subcommissural Organ;Serotonin;Not relevant;Female;11 Glia;Injections, Intraventricular;Neurosecretory Systems;Animals;Phagocytosis;Rats, Inbred Strains}, Medline = {87225061}, Month = {2}, Nlm_Id = {0364620}, Number = {1}, Pages = {131-42}, Pubmed = {3585416}, Title = {Microglia in the hypendyma of the rat subcommissural organ following brain lesion with serotonin neurotoxin}, Uuid = {78D23D6E-AC73-42C2-A846-630AAB05BB4D}, Volume = {16}, Year = {1987}} @article{Stagi:2005, Abstract = {The mechanism of axonal injury in inflammatory brain diseases is still unclear. Increased microglial production of nitric oxide (NO) is a common early sign in neuroinflammatory diseases. We found by fluorescence correlation spectroscopy that synaptophysin tagged with enhanced green fluorescence protein (synaptophysin-EGFP) moves anterogradely in axons of cultured neurons. Activated microglia focally inhibited the axonal movement of synaptophysin-EGFP in a NO synthase-dependent manner. Direct application of a NO donor to neurons resulted in inhibition of axonal transport of synaptophysin-EGFP and synaptotagmin I tagged with EGFP, mediated via phosphorylation of c-jun NH2-terminal kinase (JNK). Thus, overt production of reactive NO by activated microglia blocks the axonal transport of synaptic vesicle precursors via phosphorylation of JNK and could cause axonal and synaptic dysfunction.}, Author = {Stagi, Massimiliano and Dittrich, Petra S. and Frank, Nadja and Iliev, Asparouh I. and Schwille, Petra and Neumann, Harald}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {8102140}, Number = {2}, Organization = {Neuroimmunology Group, European Neuroscience Institute G{\"o}ttingen, 37073 G{\"o}ttingen, Germany.}, Pages = {352-62}, Pii = {25/2/352}, Pubmed = {15647478}, Title = {Breakdown of axonal synaptic vesicle precursor transport by microglial nitric oxide}, Uuid = {A6FAE162-80E4-4B25-805A-EBBCD4A31A25}, Volume = {25}, Year = {2005}, url = {papers/Stagi_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3887-04.2005}} @article{Staiger:2004, Abstract = {Previous analyses of the spiny layer IV neurons have almost exclusively focused on spiny stellate cells. Here we provide detailed morphological data characterizing three subpopulations of spiny neurons in slices of adolescent rats: (i) spiny stellate cells (58\%), (ii) star pyramidal cells (25\%) and (iii) pyramidal cells (17\%), which can be distinguished objectively by the preferential orientation of their dendritic stems. Spiny stellate cells lacked an apical dendrite and frequently confined their dendritic and axonal arbors to the respective column. Star pyramidal and pyramidal cells possessed an apical dendrite, which reached the supragranular layers. Their axonal arbors were similar, showing both a columnar component and transcolumnar branches with direct transbarrel projections. However, a small fraction of star pyramidal cells possessed few or even no transcolumnar branches. Electrophysiologically, all three types of neurons were either regular-spiking or intrinsically burst-spiking without a significant relation to the morphological subtypes. The basic synaptic properties of thalamic inputs were also independent of the type of target layer IV spiny neuron. All remained subthreshold and showed paired-pulse depression. In conclusion, the columnar axonal arborization of spiny stellate cells is supplemented by a significant oblique to horizontal projection pattern in pyramidal-like neurons. This offers a structural basis for either segregation or early context-dependent integration of tactile information, in a cell-type specific manner.}, Author = {Staiger, Jochen F. and Flagmeyer, Iris and Schubert, Dirk and Zilles, Karl and K{\"o}tter, Rolf and Luhmann, Heiko J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Electric Stimulation;Cell Size;Neurons;24 Pubmed search results 2008;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;Neural Pathways;Rats;Rats, Wistar;Somatosensory Cortex;Animals;comparative study ;Cells, Cultured;Male;Membrane Potentials}, Month = {6}, Nlm_Id = {9110718}, Number = {6}, Organization = {C. & O. Vogt Institute for Brain Research, Heinrich Heine University D{\"u}sseldorf, D-40001 D{\"u}sseldorf, Germany. jochen\@hirn.uni-duesseldorf.de}, Pages = {690-701}, Pii = {bhh029}, Pubmed = {15054049}, Title = {Functional diversity of layer IV spiny neurons in rat somatosensory cortex: quantitative morphology of electrophysiologically characterized and biocytin labeled cells}, Uuid = {D485D319-5E79-4AED-815A-E1D6A6AB3599}, Volume = {14}, Year = {2004}, url = {papers/Staiger_CerebCortex2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh029}} @article{Staley:1998, Abstract = {The simultaneous discharge of hippocampal CA3 pyramidal cells is a widely studied in vitro model of physiological and pathological network synchronization. This network is rapidly activated because of extensive positive feedback mediated by recurrent axon collaterals. Here we show that population-burst duration is limited by depletion of the releasable glutamate pool at these recurrent synapses. Postsynaptic inhibitory conductances further limit burst duration but are not necessary for burst termination. The interval between bursts in vitro depends on the rate of replenishment of releasable glutamate vesicles and the probability of release of those vesicles at recurrent synapses. Therefore presynaptic factors controlling glutamate release at recurrent synapses regulate the probability and duration of synchronous discharges of the CA3 network.}, Author = {Staley, K. J. and Longacher, M. and Bains, J. S. and Yee, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Synapses;research support, u.s. gov't, p.h.s. ;Electric Conductivity;21 Neurophysiology;Rats;Hippocampus;research support, non-u.s. gov't ;Presynaptic Terminals;Pyramidal Cells;Neural Inhibition;Electrophysiology;Nerve Net;Animals;Glutamic Acid;24 Pubmed search results 2008;21 Epilepsy}, Month = {7}, Nlm_Id = {9809671}, Number = {3}, Organization = {Department of Neurology, University of Colorado Health Sciences Center, Denver 80262, USA.}, Pages = {201-9}, Pii = {651}, Pubmed = {10195144}, Title = {Presynaptic modulation of CA3 network activity}, Uuid = {4517173F-5538-4AC1-89DE-61C08449FEDC}, Volume = {1}, Year = {1998}, url = {papers/Staley_NatNeurosci1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/651}} @article{Staley:2005, Author = {Staley, Kevin and Scharfman, Helen}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Causality;Protein Subunits;Animals;comment;Humans;Estrous Cycle;Synaptic Transmission;Female;Epilepsy;news;Receptors, GABA-A;Anxiety Disorders;21 Neurophysiology;Neurons;Gonadal Steroid Hormones;Mice;24 Pubmed search results 2008;Neural Inhibition}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Pages = {697-9}, Pii = {nn0605-697}, Pubmed = {15917829}, Title = {A woman's prerogative}, Uuid = {5C1EF311-B026-4C46-BCD1-4914F9DC7B21}, Volume = {8}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn0605-697}} @article{Staley:2007, Abstract = {Fast ripples are EEG transients emanating from epileptic foci, but fast-ripple frequencies far exceed maximal neuronal firing rates. In this issue of Neuron, Menendez de la Prida and coworkers propose that out-of-phase firing of a subpopulation of neurons during physiological ripple activity effectively doubles the ripple frequency to produce fast ripples.}, Author = {Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Epilepsy;Electroencephalography;21 Neurophysiology;Hippocampus;Rats;comment;Electrophysiology;Animals;Membrane Potentials;Neurons;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8809320}, Number = {6}, Organization = {Neurology Department, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA. kstaley\@partners.org}, Pages = {828-30}, Pii = {S0896-6273(07)00673-3}, Pubmed = {17880888}, Title = {Neurons skip a beat during fast ripples}, Uuid = {2FDA91A0-C819-46C9-873A-3B982CF5763D}, Volume = {55}, Year = {2007}, url = {papers/Staley_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.09.005}} @article{Stalmaster:1972, Author = {Stalmaster, R. M. and Hanna, G. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Transducers;Epilepsy;Electroencephalography;Freezing;21 Epilepsy;21 Neurophysiology;Cats;Female;24 Pubmed search results 2008;Stereotaxic Techniques;Time Factors;Motor Activity;Animals;Cerebral Cortex;Trephining;Electrodes, Implanted}, Medline = {75112114}, Month = {4}, Nlm_Id = {2983306R}, Number = {2}, Pages = {313-24}, Pubmed = {4615895}, Title = {Epileptic phenomena of cortical freezing in the cat: persistent multifocal effects of discrete superficial lesions}, Uuid = {1A19B70E-F4A6-4C64-9F11-516B91CEF3F6}, Volume = {13}, Year = {1972}} @article{Standley:1998, Abstract = {Forebrains from rats of postnatal days (PND) 2, 7, 14, 21, and 30-40 were subjected to subcellular fractionation and samples from crude mitochondrial (P2, which contain synaptic plasma membranes) and microsomal (P3) fractions were used for SDS-PAGE and Western blotting with antibodies against GluR1, and GluR2/3 subunits of AMPA/GluR receptors. GluR immunoreactivity in P2 fractions increased gradually from PND 2 to PND 30. In contrast, GluR immunoreactivity in P3 fractions increased sharply at early postnatal ages, and was higher than in adults as early as at PND 7. Data were compared to postnatal changes in 3H-AMPA binding reported in various studies. Significant correlations were observed between changes in GluR immunoreactivity in P3 fractions and changes in high-affinity binding on one hand and between changes in GluR immunoreactivity in P2 fractions, and changes in low affinity binding. These data further establish that glutamate receptors present in different subcellular compartments represent different maturational states of the receptors, and suggest that changes in GluR populations could participate in mechanisms of synaptic plasticity.}, Author = {Standley, S. and Wagle, N. and Baudry, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Brain Res Dev Brain Res}, Keywords = {Receptors, AMPA/*biosynthesis;Rats, Sprague-Dawley;Ligands;Neuronal Plasticity/physiology;Rats;I-5;Electrophoresis, Polyacrylamide Gel;Prosencephalon/*growth &development/*metabolism/ultrastructure;Animal;Mitochondria/metabolism;Animals, Newborn;Subcellular Fractions/*metabolism;Synaptosomes/metabolism;Blotting, Western;Support, Non-U.S. Gov't;13 Olfactory bulb anatomy;Support, U.S. Gov't, P.H.S.}, Number = {2}, Organization = {Neuroscience Program, University of Southern California, Los Angeles, CA 90089-2520, USA. sstandle\@hbpmb.usc.edu}, Pages = {277-83.}, Title = {Developmental changes in subcellular AMPA/GluR receptor populations in rat forebrain}, Uuid = {F494D4BA-01B3-4BFD-96EB-7E1679318189}, Volume = {107}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9593938%20http://www.elsevier.com:80/cgi-bin/cas/tree/store/bresd/cas_sub/browse/browse.cgi?year=1998&volume=107&issue=2&aid=52510}} @article{Stanfield:1979, Abstract = {The histogenesis, the time of origin and the pattern of migration of the cells in the hippocampus and dentate gyrus, have been studied in normal and reeler mice. The earliest indication of a defect in the reeler hippocampus is seen on the fifteenth embryonic day (E15) which is at least 24 hours after the first indication of a defect in the neocortex. It is not until E18, that the dentate gyrus shows signs of its incipient abnormality. It appears then, that in both the hippocampus and the dentate gyrus the gene defect first manifests itself at the stage at which the definitive cellular layers are assembled. Experiments involving the injection of 3H-thymidine (3H-TdR) at different developmental stages have confirmed that the site and rate of cellular proliferation in the reeler hippocampus and dentate gyrus are normal, as is the initial pattern of cell migration. However, in the reeler dentate gyrus, most postnatal cell proliferation occurs ectopically and in the hippocampus the normal "inside-out" sequence of neurogenesis is reversed, the earliest pyramidal cells generated coming to lie superficially within the stratum pyramidale and the later formed cells being added at progressively deeper levels. There is no discernible gradient in the time of origin of the granule cells in the radial dimension of the reeler dentate gyrus, whereas there is an obvious "outside-in" gradient in the normal animal. The characteristic gradients in cell proliferation seen in the transverse and longitudinal dimensions of the normal dentate gyrus are, however, also evident in the reeler mouse. Taken together, these observations suggest that the reeler gene exerts its effect on neuronal position only in the radial dimension, and does so at a stage of development subsequent to the proliferation and initial migration of the relevant neurons. Timm's sulfide silver preparations indicate that the characteristic staining patterns seen in the dentate gyrus and hippocampus appear at the same time, and mature at the same rate in normal and reeler mice.}, Author = {Stanfield, B. B. and Cowan, W. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:32 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Staining and Labeling;10 Development;Species Specificity;Comparative Study;10 Hippocampus;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Autoradiography;Mice, Inbred C57BL;Mitosis;Morphogenesis;Animals;Cell Movement;Mice;Mice, Neurologic Mutants}, Medline = {79173521}, Month = {6}, Nlm_Id = {0406041}, Number = {3}, Pages = {423-59}, Pubmed = {86549}, Title = {The development of the hippocampus and dentate gyrus in normal and reeler mice}, Uuid = {07258895-D5E9-4A42-A133-B44978EFD3F0}, Volume = {185}, Year = {1979}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901850303}} @article{Stanfield:1979a, Abstract = {The morphology of the hippocampus and dentate gyrus in normal and reeler mice has been studied in Nissl, myelin, Golgi, Timm's sulfide silver and gold chloride-sublimate preparations. It is evident from both cell-and fiber-stained sections that despite the obvious defect in the positioning of the hippocampal pyramidal and dentate granule cells in the reeler mouse within the radial dimension, the hippocampal formation as a whole shows a normal and consistent progression of cytoarchitectonic fields along its transverse axis, and a normal and consistent progression of changes in the structure of the hippocampus and dentate gyrus along their longitudinal axes. Thus, at least in these structures, the reeler gene seems to exert its effect only in the radial dimension. Cell counts in the area dentata indicate that the number of dentate granule cells in the reeler mouse is reduced compared to that found in normal or heterozygous animals. Although it has been known for some time that the number of granule cells in the reeler cerebellar cortex is markedly reduced, this appears to be the first evidence for a reduction in cell number in a forebrain structure. All the major cell types normally found in the hippocampus and the dentate gyrus are recognizable in Golgi-stained preparations from the brains of reeler mutants. However, in both regions there are a number of abnormalities in the appearance of the cells which seem to be related to the cellular ectopia. Thus, whereas most of the pyramidal and granule cells which attain a normal position in the mutant usually have normal, or near-normal dendritic arbors, the dendrites of nearly all ectopic cells are severely distorted, both in their orientation and general configuration. In preparations stained by the Timm's sulfide silver technique it is evident that the general lamination pattern seen in normal mice is retained in the reeler hippocampus and dentate gyrus despite the gross malpositioning of many of the relevant neurons. However, although the overall laminar arrangement is preserved, there are some fairly consistent abnormalities; for example, the normal trilaminar staining pattern seen in the stratum moleculare of the dentate gyrus is replaced in the reeler by a bilaminar pattern. In gold chloride-sublimate impregnated preparations there is no obvious alignment of the astrocytes in the stratum moleculare of the dentate gyrus in either normal or reeler mice. Moreover, the distribution of the astrocytes within this zone is fairly normal in the reeler mouse, although, in general, these cells appear to be more consistently stellate in form than in normal animals.}, Author = {Stanfield, B. B. and Cowan, W. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {10 Development;Heterozygote;Hippocampus;10 Hippocampus;Astrocytes;Research Support, U.S. Gov't, P.H.S.;Cell Count;Animals;Male;Mice;Neurons;Mice, Neurologic Mutants}, Medline = {79173520}, Month = {6}, Nlm_Id = {0406041}, Number = {3}, Pages = {393-422}, Pubmed = {438366}, Title = {The morphology of the hippocampus and dentate gyrus in normal and reeler mice}, Uuid = {5017A2ED-58DA-4F3A-B453-B59C734A91F9}, Volume = {185}, Year = {1979}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901850302}} @article{Stanfield:1979b, Abstract = {The organization of certain of the major afferents to the hippocampus and dentate gyrus has been studied in normal and reeler mutant mice using the autoradiographic and the anterograde degeneration methods. The distribution of the hippocampal and dentate afferents which arise in the medial and lateral parts of the entorhinal cortex and the hippocampus of both sides, has been found to be generally similar to that previously described in the rat, but there are a few minor differences that are discussed in the text. Despite the marked ectopia of many of the neurons in the hippocampal formation in the reeler mouse, the principal afferents to the hippocampus and the dentate gyrus maintain many of the features seen in normal mice. In particular, they maintain a normal radial sequence and a characteristic laminated and complementary arrangement. However, there are a number of significant differences in their distribution; for example, in the reeler mouse, the entorhinal afferents occupy the entire radial extent of the stratum moleculare of the dentate gyrus, whereas in normal mice they are restricted to the outer four-fifths of this layer. Furthermore, in the mutant the commissural and associational afferents to the dentate gyrus do not occupy the inner one-fifth of the molecular layer (as they do in normal animals) but rather are spread throughout the zone containing granule cells, which includes both the poorly-defined stratum granulosum and most of the hilar region of the dentate gyrus. Some of the developmental and functional implications of these and other abnormalities in the organization of the afferents to the hippocampus and dentate gyrus are discussed.}, Author = {Stanfield, B. B. and Caviness, V. S. and Cowan, W. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {10 Development;Limbic System;10 Hippocampus;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Neural Pathways;Comparative Study;Autoradiography;Brain Mapping;Neurons, Afferent;Mice;Animals;Mice, Neurologic Mutants}, Medline = {79173522}, Month = {6}, Nlm_Id = {0406041}, Number = {3}, Pages = {461-83}, Pubmed = {438367}, Title = {The organization of certain afferents to the hippocampus and dentate gyrus in normal and reeler mice}, Uuid = {FA05F526-32B4-40EB-9A96-8A1F777C557C}, Volume = {185}, Year = {1979}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.901850304}} @article{Star:2002, Abstract = {Dendritic spines are motile structures that contain high concentrations of filamentous actin. Using hippocampal neurons expressing fluorescent actin and the method of fluorescence recovery after photobleaching, we found that 85 +/- 2\%of actin in the spine was dynamic, with a turnover time of 44.2 +/- 4.0 s. The rapid turnover is not compatible with current models invoking a large population of stable filaments and static coupling of filaments to postsynaptic components. Low-frequency stimulation known to induce long-term depression in these neurons stabilized nearly half the dynamic actin in the spine. This effect depended on the activation of N-methyl-D-aspartate (NMDA) receptors and the influx of calcium. In neurons from mice lacking gelsolin, a calcium-dependent actin-binding protein, activity-dependent stabilization of actin was impaired. Our studies provide new information on the kinetics of actin turnover in spines, its regulation by neural activity and the mechanisms involved in this regulation.}, Author = {Star, Erin N. and Kwiatkowski, David J. and Murthy, Venkatesh N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Mice, Inbred BALB C;Cytochalasin D;Animals;Synapses;Cells, Cultured;Rats;Peptides, Cyclic;research support, u.s. gov't, p.h.s. ;Patch-Clamp Techniques;Indicators and Reagents;Mice, Transgenic;Hippocampus;Calcium;Microscopy, Fluorescence;Depsipeptides;Green Fluorescent Proteins;Dendrites;research support, non-u.s. gov't ;Animals, Newborn;Recombinant Fusion Proteins;21 Neurophysiology;Neurons;Mice;24 Pubmed search results 2008;Actins;Luminescent Proteins;Gelsolin;Receptors, N-Methyl-D-Aspartate}, Month = {3}, Nlm_Id = {9809671}, Number = {3}, Organization = {Department of Molecular & Cellular Biology, Harvard University, 16 Divinity Ave., Cambridge, Massachusetts 02138, USA.}, Pages = {239-46}, Pii = {nn811}, Pubmed = {11850630}, Title = {Rapid turnover of actin in dendritic spines and its regulation by activity}, Uuid = {E0A446E4-09ED-4B49-A200-BD66165A44EB}, Volume = {5}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn811}} @article{Steele:2006, Abstract = {The misfolding of the prion protein (PrP(c)) is a central event in prion diseases, yet the normal function of PrP(c) remains unknown. PrP(c) has putative roles in many cellular processes including signaling, survival, adhesion, and differentiation. Given the abundance of PrP(c) in the developing and mature mammalian CNS, we investigated the role of PrP(c) in neural development and in adult neurogenesis, which occurs constitutively in the dentate gyrus (DG) of the hippocampus and in the olfactory bulb from precursors in the subventricular zone (SVZ)/rostral migratory stream. In vivo, we find that PrP(c) is expressed immediately adjacent to the proliferative region of the SVZ but not in mitotic cells. In vivo and in vitro studies further find that PrP(c) is expressed in multipotent neural precursors and mature neurons but is not detectable in glia. Loss- and gain-of-function experiments demonstrate that PrP(c) levels correlate with differentiation of multipotent neural precursors into mature neurons in vitro and that PrP(c) levels positively influence neuronal differentiation in a dose-dependent manner. PrP(c) also increases cellular proliferation in vivo; in the SVZ, PrP(c) overexpresser (OE) mice have more proliferating cells compared with wild-type (WT) or knockout (KO) mice; in the DG, PrP(c) OE and WT mice have more proliferating cells compared with KO mice. Our results demonstrate that PrP(c) plays an important role in neurogenesis and differentiation. Because the final number of neurons produced in the DG is unchanged by PrP(c) expression, other factors must control the ultimate fate of new neurons.}, Author = {Steele, Andrew D. and Emsley, Jason G. and Ozdinler, P. Hande and Lindquist, Susan and Macklis, Jeffrey D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Aging;Cell Differentiation;Research Support, Non-U.S. Gov't;Mice, Knockout;Gene Expression Regulation, Developmental;Cell Proliferation;Stem Cells;Research Support, N.I.H., Extramural;Prions;Nervous System;Animals;Cells, Cultured;Mice;Neurons;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {7505876}, Number = {9}, Organization = {Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, 02142, USA.}, Pages = {3416-21}, Pii = {0511290103}, Pubmed = {16492732}, Title = {Prion protein (PrPc) positively regulates neural precursor proliferation during developmental and adult mammalian neurogenesis}, Uuid = {239C09C9-FF6E-4170-B55B-F27787B04639}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0511290103}} @article{Stefanovic:1998, Abstract = {The mechanisms of Golgi impregnation of neurons has remained enigmatic for decades. Recently, it was suggested that divalent (di)chromate anions play a role in the Golgi impregnation process. Therefore, we incubated slices of (para)formaldehyde-fixed rat brain tissue in solutions of potassium (di)chromate, phosphate, chloride or nitrate at pH 6 or 7. Slices were then immersed in solutions of silver nitrate and processed for light microscopical analysis. At pH 6, dichromate probes resulted in dense and homogeneous impregnation of neuronal cytoplasm (typical impregnation). At pH 7, chromate probes showed solely partial cytoplasmic and heavy nuclear-region neuron impregnation (atypical impregnation). Phosphate probes at pH 6 resulted in typical impregnation, whereas at pH 7 phosphate probes gave atypical impregnation. Both at pH 6 and 7, chloride and nitrate probes did not yield any Golgi impregnation. These findings confirmed the pH-dependence of silver-chromate Golgi impregnation as well as the correctness of corresponding acidic silver-phosphate impregnation. Our study revealed a previously unknown, strong anion-dependence of Golgi impregnation, suggesting that hydrogenated monovalent anions are carriers of the neuron impregnation.}, Author = {Stefanovi\'{c}, B. D. and Ristanovi\'{c}, D. and Trpinac, D. and Dordevi\'{c}-Camba, V. and Lackovi\'{c}, V. and Bumbasirevi\'{c}, V. and Obradovi\'{c}, M. and Basi\'{c}, R. and Cetkovi\'{c}, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0065-1281}, Journal = {Acta Histochem}, Keywords = {Animals;Chromates;Rats;Comparative Study;Brain;23 Technique;Nitrates;Staining and Labeling;Potassium Chloride;Rats, Wistar;Hydrogen-Ion Concentration;Male;Potassium Compounds;Formaldehyde;Phosphates;Neurons;Silver Nitrate;Molecular Probes;24 Pubmed search results 2008;Tissue Fixation;Polymers}, Medline = {98249213}, Month = {4}, Nlm_Id = {0370320}, Number = {2}, Organization = {Institute of Histology, Faculty of Medicine, University of Belgrade, Yugoslavia.}, Pages = {217-27}, Pubmed = {9587632}, Title = {The acidophilic nature of neuronal Golgi impregnation}, Uuid = {50E48BE6-C508-4825-9F12-0AA8DFB51D43}, Volume = {100}, Year = {1998}} @article{Steffan:1994, Abstract = {Feline immunodeficiency virus (FIV) provokes a disease in cats characterized by histopathological lesions similar to those observed in AIDS patients. In order to determine whether endothelial cells from brain microvessels are involved in the central nervous system disease to the same extent as macrophages and microglia, cells were isolated from healthy cat brains, cultured and infected in vitro with the FIV Villefranche IFFA 1/88 strain. The isolated cells displayed typical endothelial cell ultrastructural features and were characterized further by von Willebrand factor-labelling and the binding of specific lectins such as Ulex europaeus lectin on their membrane. They were also able to take up acetylated low density lipoproteins. Two weeks after infection, significant amounts of FIV p24 antigen were detected by indirect immunofluorescence in syncytia and single cells. Concomitantly, the same antigen could be detected in the culture medium of the infected cells by an ELISA technique. Numerous viral particles as well as different steps in the process of viral budding were observed under transmission electron microscopy. The synthesis of FIV p24 antigens still occurred in cells in which replication was blocked in the G2 phase with taxol. Our results suggest the possibility of a productive infection of brain microvascular endothelial cells by FIV in vivo, which could lead to important perturbations in the functions of the blood-brain barrier.}, Author = {Steffan, A. M. and Lafon, M. E. and Gendrault, J. L. and Koehren, F. and De Monte, M. and Royer, C. and Kirn, A. and Gut, J. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0022-1317}, Journal = {J Gen Virol}, Keywords = {Animals;Cells, Cultured;Immunodeficiency Virus, Feline;Receptors, Cell Surface;Brain;Paclitaxel;Gene Products, gag;Culture Media, Conditioned;Lipoproteins, LDL;G2 Phase;11 Glia;Receptors, Mitogen;Microcirculation;Virus Replication;Microscopy, Electron;Cats;von Willebrand Factor;Endothelium, Vascular}, Medline = {95088615}, Month = {12}, Nlm_Id = {0077340}, Organization = {Intitut National de la Sant{\'e} et de la Recherche M{\'e}dicale U74, Institut de Virologie de la Facult{\'e} de M{\'e}decine, Strasbourg, France.}, Pages = {3647-53}, Pubmed = {7996160}, Title = {Feline immunodeficiency virus can productively infect cultured endothelial cells from cat brain microvessels}, Uuid = {EE946C60-4A4D-4AEF-9099-45142B484E01}, Volume = {75 ( Pt 12)}, Year = {1994}} @article{Stein:1988, Abstract = {Adult rats with lesions of the medial frontal cortex received implants of frontal cortex taken from embryos on the 19th day of gestation and placed directly into the zone of injury at 7, 14, 30, or 60 days after initial surgery. Another group was given bilateral frontal lesions, followed 20 days later by a second small lesion to enhance the release of putative neurotrophic factors. They then received transplants 7 days after this second operation. All rats began postoperative training on a spatial alternation learning task within 4 days after the implants of fetal tissue. The brain-damaged rats with transplants at 7 or 14 days after surgery significantly improved postoperative acquisition of spatial alternation. Transplants made 30 or 60 days postoperatively had no effect; these groups were as impaired as those with lesions alone. The animals given a second, "priming" lesion after a 20-day delay, followed by implants of fetal brain tissue, performed as poorly as the group with frontal cortex lesions alone.}, Author = {Stein, D. G. and Palatucci, C. and Kahn, D. and Labbe, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0735-7044}, Journal = {Behav Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Nerve Regeneration;Rats;Research Support, U.S. Gov't, P.H.S.;Time Factors;Graft Survival;Learning;Male;Animals;Rats, Inbred Strains;24 Pubmed search results 2008;Frontal Lobe}, Medline = {88209263}, Month = {4}, Nlm_Id = {8302411}, Number = {2}, Organization = {Clark University.}, Pages = {260-7, 325-6}, Pubmed = {3365321}, Title = {Temporal factors influence recovery of function after embryonic brain tissue transplants in adult rats with frontal cortex lesions}, Uuid = {29B1E832-EADE-4CE0-9FD1-6C7518E0771B}, Volume = {102}, Year = {1988}} @article{Stein:2005, Abstract = {Feline immunodeficiency virus (FIV)-based lentiviral vectors can be targeted to restricted cell types by pseudotyping with envelopes from other viruses. An FIV vector expressing bacterial beta-galactosidase (beta-gal) and pseudotyped with lymphocytic choriomeningitis virus (LCMV) envelope glycoprotein was injected into postnatal mouse brain striatum to determine neural cell-type transduction. After 3 or 7.5 weeks, the beta-gal-expressing cells included astrocytes in the striatum and in the subventricular zone (SVZ), neuroblasts along the rostral migratory stream, and neurons in the olfactory bulb. This pattern was suggestive of transduction of neural stem cells/progenitors that reside in the SVZ and continually generate olfactory bulb neurons. To test for transduction of SVZ type B astrocyte/stem cells, LCMV-pseudotyped FIV encoding Cre recombinase driven by an astrocyte-specific promoter was injected into the striatum of ROSA26 Cre reporter mice. beta-Gal expression in these mice depends on Cre recombinase-mediated DNA recombination. beta-Gal-expressing neuroblasts and neurons were detected in the rostral migratory stream and olfactory bulb, respectively, indicating that these cells derived from an astrocytic-type stem cell. Thus, LCMV (WE54)-pseudotyped FIV provides a novel vector for transducing neural stem cells/progenitors in vivo and may prove valuable as a gene transfer vector for therapy of neurodegenerative diseases.}, Author = {Stein, Colleen S. and Martins, In\^{e}s and Davidson, Beverly L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1525-0016}, Journal = {Mol Ther}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {100890581}, Number = {3}, Organization = {Program in Gene Therapy, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242, USA.}, Pages = {382-9}, Pii = {S1525-0016(04)01531-X}, Pubmed = {15727934}, Title = {The lymphocytic choriomeningitis virus envelope glycoprotein targets lentiviral gene transfer vector to neural progenitors in the murine brain}, Uuid = {29D68708-3E78-4401-BBEB-B692F93B1D97}, Volume = {11}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ymthe.2004.11.008}} @article{Steiner:2004, Abstract = {In adult hippocampal neurogenesis, new neurons appear to originate from a cell with astrocytic properties expressing glial fibrillary acidic protein (GFAP). Also, new astrocytes are generated in the adult dentate gyrus. Whereas the putative astrocyte-like progenitor cells are consistently S-100beta-negative, many new astrocytes are S-100beta-positive. Thus, it is unclear whether the GFAP-positive progenitor cells are astrocytes in a general sense or rather neural progenitor cells with certain astrocytic characteristics. We therefore investigated the development of GFAP-expressing cells in the context of adult hippocampal neurogenesis. Proliferating cells could be either GFAP-positive or doublecortin-positive (DCX), but never both, indicating two independent populations of dividing cells in the glial and neuronal lineages. Two distinct populations of cells with astroglial properties were detected-one expressing GFAP, the other co-expressing GFAP and S-100beta. We never found S-100beta-cells to be in S-phase. No overlap between neuronal and glial markers was seen at any time point. Thus, astrogenesis occurred in parallel and to some degree independent of adult neurogenesis. The uninterrupted GFAP expression in this lineage, and neuronal markers in the other lineage, argue against a late common precursor for neurogenesis and gliogenesis in the adult hippocampus. Very few newly generated microglia and no new oligodendrocytes were detected. Environmental enrichment and voluntary wheel running-two experimental paradigms with robust stimulatory effects on adult hippocampal neurogenesis-affected hippocampal astrogenesis differentially: Running, but not enrichment, strongly induced net astrogenesis (GFAP/S-100beta), but also GFAP-positive S-100beta-negative cells, which thus appear to be a transiently amplifiable intermediate population within the glial lineage. 0894-1491 Journal Article}, Author = {Steiner, B. and Kronenberg, G. and Jessberger, S. and Brandt, M. D. and Reuter, K. and Kempermann, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Glia}, Keywords = {02 Adult neurogenesis migration;03 Adult neurogenesis progenitor source;BB, G}, Number = {1}, Organization = {Max Delbruck Center for Molecular Medicine (MDC) Berlin-Buch, Berlin, Germany.}, Pages = {41-52}, Title = {Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice}, Uuid = {8DA2A2F9-0018-4FB3-B703-42E83BBE9DEA}, Volume = {46}, Year = {2004}, url = {papers/Steiner_Glia2004.pdf}} @article{Stellwagen:2006, Abstract = {Two general forms of synaptic plasticity that operate on different timescales are thought to contribute to the activity-dependent refinement of neural circuitry during development: (1) long-term potentiation (LTP) and long-term depression (LTD), which involve rapid adjustments in the strengths of individual synapses in response to specific patterns of correlated synaptic activity, and (2) homeostatic synaptic scaling, which entails uniform adjustments in the strength of all synapses on a cell in response to prolonged changes in the cell's electrical activity. Without homeostatic synaptic scaling, neural networks can become unstable and perform suboptimally. Although much is known about the mechanisms underlying LTP and LTD, little is known about the mechanisms responsible for synaptic scaling except that such scaling is due, at least in part, to alterations in receptor content at synapses. Here we show that synaptic scaling in response to prolonged blockade of activity is mediated by the pro-inflammatory cytokine tumour-necrosis factor-alpha (TNF-alpha). Using mixtures of wild-type and TNF-alpha-deficient neurons and glia, we also show that glia are the source of the TNF-alpha that is required for this form of synaptic scaling. We suggest that by modulating TNF-alpha levels, glia actively participate in the homeostatic activity-dependent regulation of synaptic connectivity.}, Author = {Stellwagen, David and Malenka, Robert C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {0410462}, Number = {7087}, Organization = {Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, California 94304-5485, USA.}, Pages = {1054-9}, Pii = {nature04671}, Pubmed = {16547515}, Title = {Synaptic scaling mediated by glial TNF-alpha}, Uuid = {57B12D27-8C1F-4C11-9A86-AB93640AEBAD}, Volume = {440}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature04671}} @article{Stence:2001, Abstract = {The dynamics of microglial cell activation was studied in freshly prepared rat brain tissue slices. Microglia became activated in the tissue slices, as evidenced by their conversion from a ramified to amoeboid form within several hours in vitro. To define better the cytoarchitectural dynamics underlying microglial activation, we performed direct three-dimensional time-lapse confocal imaging of microglial cells in live brain slices. Microglia in tissue slices were stained with a fluorescent lectin conjugate, FITC-IB(4), and stacks of confocal optical sections through the tissue were collected repeatedly at intervals of 2-5 min for several hours at a time. Morphometric analysis of cells from time-lapse sequences revealed that ramified microglia progress to amoeboid macrophages through a stereotypical sequence of steps. First, in the withdrawal stage, the existing ramified branches of activating microglia do not actively extend or engulf other cells, but instead retract back (mean rate, 0.5-1.5 microm/min) and are completely resorbed into the cell body. Second, in the motility stage, a new set of dynamic protrusions, which can exhibit cycles of rapid extension and retraction (both up to 4 microm/min), abruptly emerges. Sometimes new processes begin to emerge even before the old branches are completely withdrawn. Third, in the locomotory stage, microglia begin translocating within the tissue (up to 118 microm/h) only after the new protrusions emerge. We conclude that the rapid conversion of resting ramified microglia to active amoeboid macrophages is accomplished not by converting quiescent branches to dynamic ones, but rather by replacing existing branches with an entirely new set of highly motile protrusions. This suggests that the ramified branches of resting microglia are normally incapable of rapid morphological dynamics necessary for activated microglial function. More generally, our time-lapse observations identify changes in the dynamic behavior of activating microglia and thereby help define distinct temporal and functional stages of activation for further investigation.}, Author = {Stence, N. and Waite, M. and Dailey, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Microscopy, Confocal;Research Support, Non-U.S. Gov't;Image Processing, Computer-Assisted;Rats;Hippocampus;Microscopy, Video;11 Glia;Microglia;Organ Culture Techniques;Animals;Cell Movement;24 Pubmed search results 2008}, Medline = {21135754}, Month = {3}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Biological Sciences, 355 Biology Building, University of Iowa, Iowa City, IA 52242, USA.}, Pages = {256-66}, Pii = {10.1002/1098-1136(200103)33:3<256::AID-GLIA1024>3.0.CO;2-J}, Pubmed = {11241743}, Title = {Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices}, Uuid = {8E346440-972E-4CF4-BD61-6267EDF701FB}, Volume = {33}, Year = {2001}, url = {papers/Stence_Glia2001.pdf}} @article{Stenman:2003, Abstract = {The lateral ganglionic eminence (LGE) is known to give rise to striatal projection neurons as well as interneurons, which migrate in the rostral migratory stream (RMS) to populate the granule cell and glomerular layers of the olfactory bulb. Because all of these neuronal subtypes express Distalless-related (DLX) homeobox proteins during their differentiation, we set out to further characterize progenitors in the Dlx-positive domain of the LGE. Previous studies have shown that the LIM homeobox protein Islet1 (ISL1) marks the LGE subventricular zone (SVZ) and differentiating striatal projection neurons. However, ISL1 is not expressed in neurons of the developing olfactory bulb or the RMS. We show here that the dorsal-most portion of the Dlx-expressing region of the LGE SVZ lacks ISL1 cells. This dorsal domain, however, contains cells that express the ETS transcription factor Er81, which is also expressed in granule and periglomerular cells of the developing and adult olfactory bulb. Moreover, the adult SVZ and RMS contain numerous Er81-positive cells. Fate-mapping studies using Dlx5/6-cre transgenic mice demonstrate that Er81-positive cells in the granule cell and glomerular layers of the olfactory bulb derive from the Dlx-expressing SVZ region. These findings suggest that the LGE SVZ contains two distinct progenitor populations: a DLX(+);ISL1(+) population representing striatal progenitors and a DLX(+);Er81(+) population comprising olfactory bulb interneuron progenitors. In support of this, mice mutant for the homeobox genes Gsh2 and Gsh1/2, which show olfactory bulb defects, exhibit dramatically reduced numbers of Er81-positive cells in the LGE SVZ as well as in the olfactory bulb mantle. 1529-2401 Journal Article}, Author = {Stenman, J. and Toresson, H. and Campbell, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {J Neurosci}, Keywords = {Interneurons/chemistry/cytology;BB both;Animals;DNA-Binding Proteins/analysis;Neurons/chemistry/cytology;Transcription Factors/analysis;Corpus Striatum/cytology/*embryology;Stem Cells/*chemistry/metabolism;Mutation;02 Adult neurogenesis migration;Homeodomain Proteins/analysis/genetics/metabolism;Mice, Transgenic;Integrases/genetics;Olfactory Bulb/cytology/*embryology/growth &development;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;Telencephalon/chemistry/*cytology/*embryology;Mice;Viral Proteins/genetics;Ganglia/cytology;Luminescent Proteins/genetics}, Number = {1}, Organization = {Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.}, Pages = {167-74}, Pubmed = {12514213}, Title = {Identification of two distinct progenitor populations in the lateral ganglionic eminence: implications for striatal and olfactory bulb neurogenesis}, Uuid = {A26DD238-C8F9-4677-9FA2-ECF7709E3B7E}, Volume = {23}, Year = {2003}, url = {papers/Stenman_JNeurosci2003.pdf}} @article{Stenman:2003a, Abstract = {We showed previously that the orphan nuclear receptor Tlx is required for the correct establishment of the pallio-subpallial boundary. Loss of Tlx results in a dorsal expansion of ventral markers (e.g., the homeodomain protein GSH2) into the ventralmost pallial region, i.e., the ventral pallium. We also observed a disproportionate reduction in the size of the Tlx mutant lateral ganglionic eminence (LGE) from embryonic day 14.5 onward. Here we show that this reduction is caused, at least in large part, by a proliferation defect. Interestingly, in Tlx mutants, the LGE derivatives are differentially affected. Although the development of the Tlx mutant striatum is compromised, an apparently normal number of olfactory bulb interneurons are observed. Consistent with this observation, we found that Tlx is required for the normal establishment of the ventral LGE that gives rise to striatal projection neurons. This domain is reduced by the dorsal and ventral expansion of molecular markers normally confined to progenitor domains flanking the ventral LGE. Finally, we investigated possible genetic interactions between Gsh2 and Tlx in lateral telencephalic development. Our results show that, although Gsh2 and Tlx have additive effects on striatal development, they differentially regulate the establishment of ventral pallial identity.}, Author = {Stenman, Jan M. and Wang, Bei and Campbell, Kenneth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008;10 Development;Telencephalon;Research Support, Non-U.S. Gov't;Receptors, Cytoplasmic and Nuclear;Antigens, Differentiation;Research Support, U.S. Gov't, P.H.S.;Corpus Striatum;Cell Division;Mice, Mutant Strains;Body Patterning;Animals;Mice;Nervous System Malformations;Homeodomain Proteins;Bromodeoxyuridine}, Medline = {22989841}, Month = {11}, Nlm_Id = {8102140}, Number = {33}, Organization = {Division of Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio 45229-3039, USA.}, Pages = {10568-76}, Pii = {23/33/10568}, Pubmed = {14627641}, Title = {Tlx controls proliferation and patterning of lateral telencephalic progenitor domains}, Uuid = {F1ABB797-2B7E-48E4-9BCB-F87ADF9D4768}, Volume = {23}, Year = {2003}} @article{Steriade:2001, Abstract = {Data from in vivo and in vitro experiments are discussed to emphasize that synaptic activities in neocortex and thalamus have a decisive impact on intrinsic neuronal properties in intact-brain preparations under anesthesia and even more so during natural states of vigilance. Thus the firing patterns of cortical neuronal types are not inflexible but may change with the level of membrane potential and during periods rich in synaptic activity. The incidences of some cortical cell classes (defined by their responses to depolarizing current pulses) are different in isolated cortical slabs in vivo or in slices maintained in vitro compared with the intact cortex of naturally awake animals. Network activities, which include the actions of generalized modulatory systems, have a profound influence on the membrane potential, apparent input resistance, and backpropagation of action potentials. The analysis of various oscillatory types leads to the conclusion that in the intact brain, there are no "pure" rhythms, generated in simple circuits, but complex wave sequences (consisting of different, low- and fast-frequency oscillations) that result from synaptic interactions in corticocortical and corticothalamic neuronal loops under the control of activating systems arising in the brain stem core or forebrain structures. As an illustration, it is shown that the neocortex governs the synchronization of network or intrinsically generated oscillations in the thalamus. The rhythmic recurrence of spike bursts and spike trains fired by thalamic and cortical neurons during states of decreased vigilance may lead to plasticity processes in neocortical neurons. If these phenomena, which may contribute to the consolidation of memory traces, are not constrained by inhibitory processes, they induce seizures in which the neocortex initiates the paroxysms and controls their thalamic reflection. The results indicate that intact-brain preparations are necessary to investigate global brain functions such as behavioral states of vigilance and paroxysmal activities.}, Author = {Steriade, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {24 Pubmed search results 2008;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;Neural Pathways;Animals;Thalamus;Cerebral Cortex;review;Neurons}, Month = {7}, Nlm_Id = {0375404}, Number = {1}, Organization = {Laboratoire de Neurophysiologie, Facult{\'e} de M{\'e}decine, Universit{\'e} Laval, Quebec G1K 7P4, Canada. mircea.steriade\@phs.ulaval.ca}, Pages = {1-39}, Pubmed = {11431485}, Title = {Impact of network activities on neuronal properties in corticothalamic systems}, Uuid = {82538BEF-18E9-4484-9512-DA8022C1B20C}, Volume = {86}, Year = {2001}} @article{Steriade:2001a, Abstract = {In this first intracellular study of neocortical activities during waking and sleep states, we hypothesized that synaptic activities during natural states of vigilance have a decisive impact on the observed electrophysiological properties of neurons that were previously studied under anesthesia or in brain slices. We investigated the incidence of different firing patterns in neocortical neurons of awake cats, the relation between membrane potential fluctuations and firing rates, and the input resistance during all states of vigilance. In awake animals, the neurons displaying fast-spiking firing patterns were more numerous, whereas the incidence of neurons with intrinsically bursting patterns was much lower than in our previous experiments conducted on the intact-cortex or isolated cortical slabs of anesthetized cats. Although cortical neurons displayed prolonged hyperpolarizing phases during slow-wave sleep, the firing rates during the depolarizing phases of the slow sleep oscillation was as high during these epochs as during waking and rapid-eye-movement sleep. Maximum firing rates, exceeding those of regular-spiking neurons, were reached by conventional fast-spiking neurons during both waking and sleep states, and by fast-rhythmic-bursting neurons during waking. The input resistance was more stable and it increased during quiet wakefulness, compared with sleep states. As waking is associated with high synaptic activity, we explain this result by a higher release of activating neuromodulators, which produce an increase in the input resistance of cortical neurons. In view of the high firing rates in the functionally disconnected state of slow-wave sleep, we suggest that neocortical neurons are engaged in processing internally generated signals.}, Author = {Steriade, M. and Timofeev, I. and Grenier, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Sleep;Sleep Stages;24 Pubmed search results 2008;21 Neurophysiology;Cats;Action Potentials;research support, non-u.s. gov't ;Polysomnography;Wakefulness;Neocortex;Synaptic Transmission;Animals;comparative study ;Membrane Potentials;Neurons;Periodicity}, Month = {5}, Nlm_Id = {0375404}, Number = {5}, Organization = {Laboratoire de Neurophysiologie, Facult{\'e} de M{\'e}dicine, Universit{\'e} Laval, Quebec G1K 7P4, Canada. mircea.steriade\@phs.ulaval.ca}, Pages = {1969-85}, Pubmed = {11353014}, Title = {Natural waking and sleep states: a view from inside neocortical neurons}, Uuid = {143C46D8-50D8-4F11-9474-B2B590BCED5A}, Volume = {85}, Year = {2001}, url = {papers/Steriade_JNeurophysiol2001.pdf}} @article{Steriade:2004, Abstract = {1471-003x Journal Article}, Author = {Steriade, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {18 Classic Neuroanatomy Physiology;M pdf}, Number = {2}, Organization = {Laboratoire de Neurophysiologie, Faculte de Medecine, Universite Laval, Quebec, Canada G1K 7P4. mircea.steriade\@phs.ulaval.ca}, Pages = {121-34}, Title = {Neocortical cell classes are flexible entities}, Uuid = {E1128D80-5AF4-4AE3-8BBA-B24B277A6C24}, Volume = {5}, Year = {2004}, url = {papers/Steriade_NatRevNeurosci2004.pdf}} @article{Stettler:2006, Abstract = {While recent studies of synaptic stability in adult cerebral cortex have focused on dendrites, how much axons change is unknown. We have used advances in axon labeling by viruses and in vivo two-photon microscopy to investigate axon branching and bouton dynamics in primary visual cortex (V1) of adult Macaque monkeys. A nonreplicative adeno-associated virus bearing the gene for enhanced green fluorescent protein (AAV.EGFP) provided persistent labeling of axons, and a custom-designed two-photon microscope enabled repeated imaging of the intact brain over several weeks. We found that large-scale branching patterns were stable but that a subset of small branches associated with terminaux boutons, as well as a subset of en passant boutons, appeared and disappeared every week. Bouton losses and gains were both approximately 7\%of the total population per week, with no net change in the overall density. These results suggest ongoing processes of synaptogenesis and elimination in adult V1.}, Author = {Stettler, Dan D. and Yamahachi, Homare and Li, Wu and Denk, Winfried and Gilbert, Charles D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {The Rockefeller University, New York, New York, USA.}, Pages = {877-87}, Pii = {S0896-6273(06)00135-8}, Pubmed = {16543135}, Title = {Axons and synaptic boutons are highly dynamic in adult visual cortex}, Uuid = {F5F4971C-B33D-4125-99D7-6B63744E2FED}, Volume = {49}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.02.018}} @article{Stevens:2007, Abstract = {During development, the formation of mature neural circuits requires the selective elimination of inappropriate synaptic connections. Here we show that C1q, the initiating protein in the classical complement cascade, is expressed by postnatal neurons in response to immature astrocytes and is localized to synapses throughout the postnatal CNS and retina. Mice deficient in complement protein C1q or the downstream complement protein C3 exhibit large sustained defects in CNS synapse elimination, as shown by the failure of anatomical refinement of retinogeniculate connections and the retention of excess retinal innervation by lateral geniculate neurons. Neuronal C1q is normally downregulated in the adult CNS; however, in a mouse model of glaucoma, C1q becomes upregulated and synaptically relocalized in the adult retina early in the disease. These findings support a model in which unwanted synapses are tagged by complement for elimination and suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease.}, Author = {Stevens, Beth and Allen, Nicola J. and Vazquez, Luis E. and Howell, Gareth R. and Christopherson, Karen S. and Nouri, Navid and Micheva, Kristina D. and Mehalow, Adrienne K. and Huberman, Andrew D. and Stafford, Benjamin and Sher, Alexander and Litke, Alan M. and Lambris, John D. and Smith, Stephen J. and John, Simon W. M. and Barres, Ben A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Long-Term Synaptic Depression;10 Development;Retina;Animals;Astrocytes;Synapses;Up-Regulation;Complement C1q;RNA, Messenger;research support, non-u.s. gov't;10 circuit formation;Animals, Newborn;Mice, Knockout;Mice, Inbred DBA;Complement Activation;research support, n.i.h., extramural;Mice;Central Nervous System;24 Pubmed search results 2008;Complement C3;Geniculate Bodies;Glaucoma;Retinal Ganglion Cells}, Month = {12}, Nlm_Id = {0413066}, Number = {6}, Organization = {Department of Neurobiology, Stanford University School of Medicine, Stanford, CA 94305, USA. beths\@standfordmedalumni.org}, Pages = {1164-78}, Pii = {S0092-8674(07)01355-4}, Pubmed = {18083105}, Title = {The classical complement cascade mediates CNS synapse elimination}, Uuid = {66D0A897-7431-4778-BDD1-B5E9D6693967}, Volume = {131}, Year = {2007}, url = {papers/Stevens_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2007.10.036}} @article{Stevenson:2001, Abstract = {In Drosophila syncytial blastoderm embryos, centrosomes specify the position of actin-based interphase caps and mitotic furrows. Mutations in the scrambled locus prevent assembly of mitotic furrows, but do not block actin cap formation. The scrambled gene encodes a protein that localizes to the mitotic furrows and centrosomes. Sced localization, actin reorganization from caps into mitotic furrows, and centrosome-coordinated assembly of actin caps are not blocked by microtubule disruption. Our results indicate that centrosomes may coordinate assembly of cortical actin caps through a microtubule-independent mechanism, and that Scrambled mediates a second microtubule-independent process that drives mitotic furrow assembly. 1465-7392 Journal Article}, Author = {Stevenson, V. A. and Kramer, J. and Kuhn, J. and Theurkauf, W. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Nat Cell Biol}, Keywords = {Animals;Microtubules/drug effects/*genetics/ultrastructure;Insect Proteins/*genetics/metabolism;Centrosome/*metabolism/ultrastructure;Colchicine/pharmacology;EE pdf;Actins/*genetics/ultrastructure;Cell Cycle Proteins/*genetics/metabolism;08 Aberrant cell cycle;Cytochalasin D/pharmacology;Mitosis/drug effects/*physiology;Embryo/cytology/*embryology/metabolism;Polymers/metabolism;Mutation/physiology;Cytoskeleton/genetics/metabolism/ultrastructure;*Drosophila Proteins;Support, U.S. Gov't, P.H.S.;Drosophila/cytology/*embryology/genetics;Blastoderm/cytology/metabolism;Interphase/physiology}, Number = {1}, Organization = {Program in Molecular Medicine and the Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, 373 Plantation Street, Worcester, Massachusetts 01605, USA.}, Pages = {68-75}, Title = {Centrosomes and the Scrambled protein coordinate microtubule-independent actin reorganization}, Uuid = {FD9B7455-DE2C-472A-9E4C-6054DDD8F36A}, Volume = {3}, Year = {2001}, url = {papers/Stevenson_NatCellBiol2001.pdf}} @article{Stewart:2002, Abstract = {The interneurons of the olfactory bulb arise from precursor cells in the anterior part of the neonatal subventricular zone, the SVZa, and are distinctive in that they possess a neuronal phenotype and yet undergo cell division. To characterize the differentiation of neonatal SVZa progenitor cells, we analyzed the complement of ionotropic neurotransmitter receptors that they express in vitro. For this analysis, we tested the sensitivity of SVZa progenitor cells to gamma- amino-n-butyric acid (GABA), adenosine triphosphate (ATP), kainate, N- methyl-D-aspartate (NMDA), and acetylcholine (ACh) after 1 day in vitro. SVZa progenitor cells had chloride currents activated by GABA and muscimol, the GABA(A) receptor-specific agonist, but were insensitive to ATP, kainate, NMDA, and ACh. In addition, GABA- or muscimol-activated chloride currents were blocked nearly completely by 30 &mgr;M bicuculline, the GABA(A) receptor-specific antagonist, suggesting that GABA(B) and GABA(C) receptors are absent. Measurements of the chloride reversal potential by gramicidin-perforated patch clamp revealed that currents generated by activation of GABA(A) receptors were inward, and thus, depolarizing. A set of complementary experiments was undertaken to determine by reverse transcription and polymerase chain reaction (RT-PCR) whether SVZa progenitor cells express the messenger RNA (mRNA) coding for glutamic acid decarboxylase 67 (GAD67), used in the synthesis of GABA and for GABA(A) receptor subunits. Both postnatal day (P0) SVZa and olfactory bulb possessed detectable mRNA coding for GAD67. In P0 SVZa, the GABA(A) receptor subunits detected with RT-PCR included alpha2-4, beta1-3, and gamma2S (short form). By comparison, the P0 olfactory bulb expressed all of the subunits detectable in the SVZa and additional subunit mRNAs: alpha1, alpha5, gamma1, gamma2L (long form), gamma3, and delta subunit mRNAs. Antibodies recognizing GABA, GAD, and various GABA(A) receptor subunits were used to label SVZa cells harvested from P0-1 rats and cultured for 1 day. The cells were immunoreactive for GABA, GAD, and the GABA(A) receptor subunits alpha2-5, beta1-3, and gamma2. To relate the characteristics of GABA(A) receptors in cultured SVZa precursor cells to particular combinations of subunits, the open reading frames of the dominant subunits detected by RT-PCR (alpha2-4, beta3, and gamma2S) were cloned into a mammalian cell expression vector and different combinations were transfected into Chinese hamster ovary-K1 (CHO-K1) cells. A comparison of the sensitivity to inhibition by zinc of GABA(A) receptors in SVZa precursor cells and in CHO-K1 cells expressing various combinations of recombinant GABA(A) receptor subunits suggested that the gamma2S subunit was present and functional in the GABA(A) receptor chloride channel complex. Thus, SVZa precursor cells are GABAergic and a subset of the GABA(A) receptor subunits detected in the olfactory bulb was found in the SVZa, as might be expected because SVZa progenitor cells migrate to the bulb as they differentiate. Copyright 2002 Wiley Periodicals, Inc. J Neurobiol 50: 305-322, 2002; DOI 10.1002/neu.10038}, Author = {Stewart, R. R. and Hoge, G. J. and Zigova, T. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:39:59 -0400}, Journal = {J Neurobiol}, Keywords = {02 Adult neurogenesis migration;BB pdf;03 Adult neurogenesis progenitor source}, Number = {4}, Organization = {Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 12420 Parklawn Drive, Bethesda, Maryland 20892-8115.}, Pages = {305-322.}, Title = {Neural progenitor cells of the neonatal rat anterior subventricular zone express functional GABA(A) receptors}, Uuid = {C2BA2644-EA8B-45E3-8943-0A2A71C7A0E6}, Volume = {50}, Year = {2002}, url = {papers/Stewart_JNeurobiol2002}} @article{Stewart:1999, Abstract = {The progenitor cells from the anterior part of the neonatal subventricular zone, the SVZa, are unusual in that, although they undergo division, they have a neuronal phenotype. To characterize the electrophysiological properties of the SVZa precursor cells, recordings were made of potassium and sodium currents from SVZa cells that were removed from postnatal day 0-1 rats and cultured for 1 day. The properties of the delayed rectifier and A-type potassium currents were described by classical Hodgkin and Huxley analyses of activation and inactivation. In addition, cells were assessed under current clamp for their ability to generate action potentials. The A-type potassium current (IK(A)) was completely inactivated at a holding potential of - 50 mV. The remaining potassium current resembled the delayed rectifier current (IK(DR)) in that it was blocked by tetraethylammonium (TEA; IC50 4.1 mM) and activated and inactivated slowly compared with IK(A). The conductance-voltage (G-V) curve revealed that G increased continuously from 0.2 nS at -40 mV to a peak of 2.6 nS at +10 or +20 mV, and then decreased for voltages above +30 mV. Activation time constants were largest at -40 mV ( approximately 11 ms) and smallest at 100 mV ( approximately 1.5 ms). The properties of IK(A) were studied in the presence of 20 mM TEA, to block IK(DR), and from a holding potential of -15 mV, to inactivate both IK(DR) and IK(A). IK(A) was then allowed to recover from inactivation to negative potentials during 200- to 800-ms pulses. Recovery from inactivation was fastest at -130 mV ( approximately 21 ms) and slowest at -90 mV ( approximately 135 ms). Inactivation was voltage independent from -60 to +60 mV with a time constant of approximately 15 ms. At steady state, IK(A) was half inactivated at -90 mV. GK(A) increased from 0.2 nS at -60 mV to a peak of 2.4 nS at +40 mV. Finally, the activation time constants ranged from approximately 1.9 ms at -50 mV to 0.7 ms at +60 mV. The properties of IK(A) resembled those of IK(A) found in differentiating cerebellar granule neurons. Most SVZa cells had sodium currents (28/32 cells). However, in current clamp 11 of 12 cells were incapable of generating action potentials from voltages of -30 to -100 mV, suggesting that the available current densities were too low to support excitability.}, Author = {Stewart, R. R. and Zigova, T. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:59 -0400}, Journal = {J Neurophysiol}, Keywords = {Electric Stimulation;Tetraethylammonium Compounds/pharmacology;Membrane Potentials/physiology;Prosencephalon/cytology/*metabolism;Rats;Cerebral Ventricles/cytology/*metabolism;Animals, Newborn/*physiology;Animal;Potassium Channels/*metabolism;Support, U.S. Gov't, P.H.S.;Electrophysiology;Patch-Clamp Techniques;13 Olfactory bulb anatomy;I both}, Number = {1}, Organization = {Laboratory of Molecular and Cellular Neurobiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892-8115, USA.}, Pages = {95-102.}, Title = {Potassium currents in precursor cells isolated from the anterior subventricular zone of the neonatal rat forebrain}, Uuid = {A1258A3B-A961-4498-A579-92A084C02800}, Volume = {81}, Year = {1999}, url = {papers/Stewart_JNeurophysiol1999.pdf}} @article{Stiene-Martin:2001, Abstract = {Accumulating evidence, obtained largely in vitro, indicates that opioids regulate the genesis of neurons and glia and their precursors in the nervous system. Despite this evidence, few studies have assessed opioid receptor expression in identified cells within germinal zones or examined opioid effects on gliogenesis in vivo. To address this question, the role of opioids was explored in the subventricular zone (SVZ) and/or striatum of 2-5-day-old and/or adult ICR mice. The results showed that subpopulations of neurons, astrocytes, and oligodendrocytes in the SVZ and striatum differentially express mu-, delta-, and/or kappa-receptor immunoreactivity in a cell type-specific and developmentally regulated manner. In addition, DNA synthesis was assessed by examining 5-bromo-2'-deoxyuridine (BrdU) incorporation into glial and nonglial precursors. Morphine (a preferential mu-agonist) significantly decreased the number of BrdU-labeled GFAP(+) cells compared with controls or mice co-treated with naltrexone plus morphine. Alternatively, in S100beta(+) cells, morphine did not significantly decrease BrdU incorporation; however, significant differences were noted between mice treated with morphine and those treated with morphine plus naltrexone. Most cells were GFAP(- )/S100beta(-). When BrdU incorporation was assessed within the total population (glia and nonglia), morphine had no net effect, but naltrexone alone markedly increased BrdU incorporation. This finding suggests that DNA synthesis in GFAP(-)/S100beta(-) cells is tonically suppressed by endogenous opioids. Assuming that S100beta and GFAP, respectively, distinguish among younger and older astroglia, this implies that astroglial replication becomes increasingly sensitive to morphine during maturation, and suggests that opioids differentially regulate the development of distinct subpopulations of glia and glial precursors.}, Author = {Stiene-Martin, A. and Knapp, P. E. and Martin, K. and Gurwell, J. A. and Ryan, S. and Thornton, S. R. and Smith, F. L. and Hauser, K. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Glia}, Keywords = {Glial Fibrillary Acidic Protein/metabolism;Receptors, Opioid/drug effects/*metabolism;Lateral Ventricles/cytology/*growth &development/metabolism;Comparative Study;Calcium-Binding Proteins/metabolism;Antigens, Differentiation/metabolism;Aging/physiology;Antigens, Surface/metabolism;Animal;Mice, Inbred ICR/anatomy &histology/growth &development/metabolism;11 Glia;G abstr;Naltrexone/pharmacology;Morphine/pharmacology;Neostriatum/cytology/*growth &development/metabolism;Opioid Peptides/metabolism;Animals, Newborn/anatomy &histology/growth &development/metabolism;Oligodendroglia/cytology/drug effects/*metabolism;Cell Differentiation/drug effects/physiology;Nerve Growth Factors/metabolism;Support, U.S. Gov't, P.H.S.;Amino Acid Transport System X-AG/metabolism;Mice;Astrocytes/cytology/drug effects/*metabolism;Immunohistochemistry;Bromodeoxyuridine/pharmacokinetics;Cell Division/drug effects/*physiology;Neurons/cytology/drug effects/*metabolism}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.}, Pages = {78-88.}, Title = {Opioid system diversity in developing neurons, astroglia, and oligodendroglia in the subventricular zone and striatum: impact on gliogenesis in vivo}, Uuid = {C174C104-3215-4351-9563-46D0653D403B}, Volume = {36}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11571786}} @article{Stockinger:2005, Abstract = {Male-specific fruitless (fru) products (Fru(M)) are both necessary and sufficient to "hardwire" the potential for male courtship behavior into the Drosophila nervous system. Fru(M) is expressed in approximately 2\%of neurons in the male nervous system, but not in the female. We have targeted the insertion of GAL4 into the fru locus, allowing us to visualize and manipulate the Fru(M)-expressing neurons in the male as well as their counterparts in the female. We present evidence that these neurons are directly and specifically involved in male courtship behavior and that at least some of them are interconnected in a circuit. This circuit includes olfactory neurons required for the behavioral response to sex pheromones. Anatomical differences in this circuit that might account for the dramatic differences in male and female sexual behavior are not apparent.}, Author = {Stockinger, Petra and Kvitsiani, Duda and Rotkopf, Shay and Tiri{\'a}n, L{\'a}szl{\'o} and Dickson, Barry J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0413066}, Number = {5}, Organization = {Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria.}, Pages = {795-807}, Pii = {S0092-8674(05)00406-X}, Pubmed = {15935765}, Title = {Neural circuitry that governs Drosophila male courtship behavior}, Uuid = {3A1E6911-8603-4A53-A001-586DD633A397}, Volume = {121}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2005.04.026}} @article{Stosiek:2003, Abstract = {Two-photon calcium imaging is a powerful means for monitoring the activity of distinct neurons in brain tissue in vivo. In the mammalian brain, such imaging studies have been restricted largely to calcium recordings from neurons that were individually dye-loaded through microelectrodes. Previous attempts to use membrane-permeant forms of fluorometric calcium indicators to load populations of neurons have yielded satisfactory results only in cell cultures or in slices of immature brain tissue. Here we introduce a versatile approach for loading membrane-permeant fluorescent indicator dyes in large populations of cells. We established a pressure ejection-based local dye delivery protocol that can be used for a large spectrum of membrane-permeant indicator dyes, including calcium green-1 acetoxymethyl (AM) ester, Fura-2 AM, Fluo-4 AM, and Indo-1 AM. We applied this dye-loading protocol successfully in mouse brain tissue at any developmental stage from newborn to adult in vivo and in vitro. In vivo two-photon Ca2+ recordings, obtained by imaging through the intact skull, indicated that whisker deflection-evoked Ca2+ transients occur in a subset of layer 2/3 neurons of the barrel cortex. Thus, our results demonstrate the suitability of this technique for real-time analyses of intact neuronal circuits with the resolution of individual cells.}, Author = {Stosiek, Christoph and Garaschuk, Olga and Holthoff, Knut and Konnerth, Arthur}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Mice, Inbred BALB C;Fluorescent Dyes;Electric Stimulation;Calcium Signaling;In Vitro;Animals;Glutamic Acid;Brain;in vitro ;Staining and Labeling;Physical Stimulation;Microscopy, Fluorescence;21 Calcium imaging;research support, non-u.s. gov't ;Nerve Net;21 Neurophysiology;Photons;Mice;Research Support, Non-U.S. Gov't;optical physiology;optical imaging;in vivo;multiphoton}, Medline = {22684521}, Month = {6}, Nlm_Id = {7505876}, Number = {12}, Organization = {Physiologisches Institut, Ludwig-Maximilians Universit{\"a}t M{\"u}nchen, Pettenkoferstrasse 12, 80336 Munich, Germany.}, Pages = {7319-24}, Pii = {1232232100}, Pubmed = {12777621}, Title = {In vivo two-photon calcium imaging of neuronal networks}, Uuid = {A2735F15-3CD3-4148-86C1-933C1CF8CE6D}, Volume = {100}, Year = {2003}, url = {papers/Stosiek_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.1232232100}} @article{Stott:2006, Abstract = {In vivo application of viral vectors for gene transfer is a commonly used tool in anatomical and functional studies, as well as in development of neuroprotective and restorative strategies for therapy. Although the most common route of administration is via direct injection into the brain parenchyma in adult animals, a number of short-term studies have been performed in the developing central nervous system. Here we investigated the long-term transgene expression following in utero delivery of a retroviral vector encoding for the green fluorescent protein (GFP) marker gene at embryonic days 14.5-17.5 using an ultrasound-guided injection system. Intraparenchymal injections of the ganglionic eminence were compared with vector delivery to the intracerebroventricular space. Injections into the ganglionic eminences resulted in a predominantly unilateral transduction localized to the forebrain, giving rise to GFP-positive (GFP+) neurons and astrocytes in the striatum, olfactory bulb, cortex and hippocampus. When the vector was injected into the lateral ventricle, on the other hand, widespread expression of GFP was seen throughout the brain. The total number of GFP+ cells in the striatum was estimated to be between 20,000 and 50,000 cells using a computerized stereological quantification tool. Phenotypic characterization of these transduced cells using confocal microscopical analysis showed that 64\%were NeuN+ neurons, 14\%APC+ oligodendrocytes and 15\%glial cells labelled with GFAP, S100beta and Iba1, when the vector injection was performed at E14.5. Delivery into later embryos resulted in a reduction in neuronal profiles with a reciprocal increase in glial cells.}, Author = {Stott, Simon R. W. and Kirik, Deniz}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Microtubule-Associated Proteins;Pregnancy;Transduction, Genetic;Animals;Gene Expression Regulation, Developmental;Rats;comparative study;Brain;Phosphopyruvate Hydratase;Female;Cell Count;Rats, Sprague-Dawley;Ki-67 Antigen;23 Technique;Retroviridae;research support, non-u.s. gov't;Green Fluorescent Proteins;Genetic Vectors;Embryo;Neuropeptides;Sialic Acids;Somatostatin;Age Factors;Neural Cell Adhesion Molecule L1;24 Pubmed search results 2008;Immunohistochemistry;Uterus}, Month = {10}, Nlm_Id = {8918110}, Number = {7}, Organization = {CNS Disease Modelling Unit, Section of Neuroscience, Department of Experimental Medical Science, Lund University, Sweden. Simon.Stott\@med.lu.se}, Pages = {1897-906}, Pii = {EJN5095}, Pubmed = {17067293}, Title = {Targeted in utero delivery of a retroviral vector for gene transfer in the rodent brain}, Uuid = {A614A7B6-07EC-4EDF-8514-9D489739AFE5}, Volume = {24}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2006.05095.x}} @article{Stoye:2001, Abstract = {Embedded in the genomes of all vertebrates are the proviral remnants of previous retroviral infections. Although the overwhelming majority has suffered inactivating mutations, current research suggests that members of one family of human retroelements may still be capable of movement.}, Author = {Stoye, J. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {15 ERVs retroelements;Humans;Endogenous Retroviruses;24 Pubmed search results 2008;Evolution, Molecular;Terminal Repeat Sequences;DNA, Viral;comment;15 Retrovirus mechanism;Animals;Proviruses;Recombination, Genetic;review;Virus Integration}, Medline = {21575979}, Month = {11}, Nlm_Id = {9107782}, Number = {22}, Organization = {National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. jstoye\@nimr.mrc.ac.uk}, Pages = {R914-6}, Pii = {S0960-9822(01)00553-X}, Pubmed = {11719237}, Title = {Endogenous retroviruses: still active after all these years?}, Uuid = {ADFF7686-AFD5-4602-891B-286245325D63}, Volume = {11}, Year = {2001}} @article{Stoye:1983, Abstract = {Germ line DNA from all strains of mice contains numerous endogenous retroviruses. One of these viruses, a virus with xenotropic host range is induced from lymphocytes of most strains by treatment with B cell mitogens. Virus induction is amplified by 5-bromo-2'-deoxyuridine (BrdU) treatment. We report here studies of the genetic control of retrovirus induction from lymphocytes in crosses between BALB/cTif mice and noninducible 129/Rrj mice. We identify a novel locus, Bdv-1, which controls the expression of a reverse transcriptase-positive, defective retrovirus in BALB/cTif lymphocytes. In addition, we confirm previous reports that xenotropic virus is controlled by a locus, Bxv-1, mapping to chromosome 1. The two loci are nonlinked and respond differently to inducing stimuli. Bxv-1 is induced mainly by BrdU and only marginally by mitogen; in contrast, Bdv-1 is induced by mitogen and BrdU has little effect. The induction of these two loci is discussed with respect to B cell differentiation.}, Author = {Stoye, J. P. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0022-1007}, Journal = {J Exp Med}, Keywords = {23 dNTPs-Brdu;Mice, Inbred BALB C;Animals;Lymphocytes;Lipopolysaccharides;Female;15 Retrovirus mechanism;Lymphocyte Activation;RNA-Directed DNA Polymerase;23 Technique;Retroviridae;11 Glia;Male;Crosses, Genetic;Virus Activation;Retroviridae Infections;Mice;24 Pubmed search results 2008;Bromodeoxyuridine;Spleen}, Medline = {83215084}, Month = {5}, Nlm_Id = {2985109R}, Number = {5}, Pages = {1660-74}, Pubmed = {6189943}, Title = {Endogenous retrovirus expression in stimulated murine lymphocytes. Identification of a new locus controlling mitogen induction of a defective virus}, Uuid = {624D3349-27FE-48D0-8970-AF3E156BB75F}, Volume = {157}, Year = {1983}, url = {papers/Stoye_JExpMed1983.pdf}} @article{Stoye:1984, Abstract = {In addition to the known induction of xenotropic endogenous virus in B-mitogen-stimulated murine lymphocyte cultures, distinguishable defective viruses were also induced in different mouse strains (NFS/N, 129, BALB/c). AKR cells produced xenotropic virus and also, in contrast to BALB/c, ecotropic virus. The drug bromodeoxyuridine appeared to have differential effects on virus expression, amplifying xenotropic virus induction but inhibiting the spontaneous production of the ecotropic virus in AKR cultures and of the defective virus in NFS/N cells. Infecting stimulated BALB/c or AKR cultures with Friend leukaemia virus resulted in the production of ecotropic-xenotropic pseudotype viruses, indicating that the infecting ecotropic virus replicates in the cells in which xenotropic virus is induced. No pseudotypes or recombinants were observed following infection of spleen cells releasing defective viruses. Friend leukaemia virus and xenotropic virus with an ecotropic envelope replicated equally well in stimulated lymphocytes from the different strains examined. Taken together, these findings indicate that the non-infectious viruses are encoded by defective proviruses, rather than resulting from faulty, host cell-controlled, virus maturation.}, Author = {Stoye, J. P. and Moroni, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0022-1317}, Journal = {J Gen Virol}, Keywords = {15 ERVs retroelements;Animals;Lipopolysaccharides;Species Specificity;Phenotype;Comparative Study;Cell Line;Lymphocytes;Rats;Gammaretrovirus;15 Retrovirus mechanism;Mink;Mice;Bromodeoxyuridine;24 Pubmed search results 2008;Lymphocyte Activation;Mice, Inbred Strains}, Medline = {84113551}, Month = {2}, Nlm_Id = {0077340}, Pages = {317-26}, Pubmed = {6319577}, Title = {Phenotypic mixing of retroviruses in mitogen-stimulated lymphocytes: analysis of xenotropic and defective endogenous mouse viruses}, Uuid = {115EE463-75EB-4503-AA19-EC84199E9EDD}, Volume = {65 ( Pt 2)}, Year = {1984}} @article{Stoye:2000, Author = {Stoye, J. P. and Coffin, J. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {15 ERVs retroelements;Pregnancy Proteins;Endogenous Retroviruses;24 Pubmed search results 2008;Female;Gene Products, env;Evolution, Molecular;Membrane Fusion;Placenta;Trophoblasts;comment;Pregnancy;Animals;Humans;Proviruses;15 Retrovirus mechanism;news}, Medline = {20155452}, Month = {2}, Nlm_Id = {0410462}, Number = {6771}, Pages = {715, 717}, Pubmed = {10693785}, Title = {A provirus put to work}, Uuid = {693791A2-7637-4343-B342-1E1229596A0F}, Volume = {403}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35001700}} @article{Stranahan:2006, Abstract = {Social isolation can exacerbate the negative consequences of stress and increase the risk of developing psychopathology. However, the influence of living alone on experiences generally considered to be beneficial to the brain, such as physical exercise, remains unknown. We report here that individual housing precludes the positive influence of short-term running on adult neurogenesis in the hippocampus of rats and, in the presence of additional stress, suppresses the generation of new neurons. Individual housing also influenced corticosterone levels-runners in both housing conditions had elevated corticosterone during the active phase, but individually housed runners had higher levels of this hormone in response to stress. Moreover, lowering corticosterone levels converted the influence of short-term running on neurogenesis in individually housed rats from negative to positive. These results suggest that, in the absence of social interaction, a normally beneficial experience can exert a potentially deleterious influence on the brain.}, Author = {Stranahan, Alexis M. and Khalil, David and Gould, Elizabeth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {Department of Psychology, Princeton University, Princeton NJ 08544.}, Pages = {526-33}, Pii = {nn1668}, Pubmed = {16531997}, Title = {Social isolation delays the positive effects of running on adult neurogenesis}, Uuid = {15965441-45DA-426F-8B7D-C5B750F0ADBD}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1668}} @article{Streit:2002, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0947-6075}, Journal = {Ernst Schering Res Found Workshop}, Keywords = {Brain Injuries;Human;Not relevant;Alzheimer Disease;Microglia;review, tutorial;11 Glia;Animals;review;Neurons}, Medline = {22062110}, Nlm_Id = {9422786}, Number = {39}, Organization = {Department of Neuroscience, P.O. Box 100244, Building 59, University of Florida, College of Medicine, 100 Newell Drive, Gainesville, FL 32611, USA. streit\@ufbi.ufl.edu}, Pages = {11-24}, Pubmed = {12066409}, Title = {Microglia and the response to brain injury}, Uuid = {EE8FC4E7-225E-4E59-BC3A-B36BC86EF60C}, Year = {2002}} @article{Streit:1994, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0937-4477}, Journal = {Eur Arch Otorhinolaryngol}, Keywords = {Facial Nerve;Cytokines;Rats;Nerve Regeneration;Motor Neurons;Not relevant;11 Glia;Microglia;Animals;Major Histocompatibility Complex}, Medline = {20236131}, Month = {12}, Nlm_Id = {9002937}, Organization = {Department of Neuroscience, U of F Health Service Center, University of Florida College of Medicine, Gainesville 32610-0244, USA.}, Pages = {S69-70}, Pubmed = {10774316}, Title = {The role of microglia in regeneration}, Uuid = {063BDC33-57FB-495A-8DFA-A94C1707F726}, Year = {1994}} @article{Streit:1989, Abstract = {The expression of immune-associated (MHC class II) antigen was studied immunohistochemically over several months in the rat facial nucleus after nerve transection and after intraneural injection of toxic ricin. Cells expressing Ia antigen were of a perivascular type and parenchymal ramified microglia. In the first few weeks after nerve lesions we observed a gradual increase in the number of Ia-immunoreactive cells starting with an initial appearance of Ia-positive perivascular cells which were succeeded by increasing numbers of Ia-positive ramified microglia. In long-term animals Ia expression was almost exclusively found in microglia. We propose (a) the existence of a population of immunocompetent perivascular cells normally present in adult rat brain that can be stimulated to express Ia antigen, and (b) the existence of a subpopulation of ramified microglia that arises through transformation of Ia-positive perivascular cells in the adult under pathological conditions.}, Author = {Streit, W. J. and Graeber, M. B. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Reference Values;Neuroglia;Motor Neurons;Nerve Regeneration;Nerve Degeneration;Rats;Histocompatibility Antigens Class II;Facial Nerve;Time Factors;Cell Survival;11 Glia;Not relevant;Denervation;Animals;Brain;Rats, Inbred Strains}, Medline = {89325514}, Month = {8}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Neuromorphology, Max Planck Institute for Psychiatry, Martinsried, Federal Republic of Germany.}, Pages = {115-26}, Pubmed = {2753113}, Title = {Expression of Ia antigen on perivascular and microglial cells after sublethal and lethal motor neuron injury}, Uuid = {B141CD81-502A-4FA0-9DA4-72057B4DDD6A}, Volume = {105}, Year = {1989}} @article{Streit:1988, Abstract = {The present review summarizes recently acquired data in vivo, which support a role of CNS microglia as a source of defense cells in the CNS capable of carrying out certain immune functions autonomously. We have kept the following discussion restricted to microglial cells and have not included work on the immunological functions of astrocytes, which has been recently reviewed elsewhere (Fontana et al.: Immunological Reviews 137:3521-3527, 1987). Resting microglia are scattered uniformly throughout the CNS forming a network of potential immunoeffector cells, which can be activated by stimuli ranging from peripheral nerve injury over viral infections to direct mechanical brain trauma. The term "activated microglia" is used here to describe proliferating cells that demonstrate changes in their immunophenotype but have not undergone transformation into brain macrophages. Such a transformation can be stimulated by neuronal death but not by sublethal neuronal injury. Microglia may function as antigen-presenting cells and may thus represent the effector cell responsible for the recruitment of lymphocytes to the brain resulting in an inflammatory reaction. The recent developments in the understanding of microglial cell function may lead to a redefinition of the often cited "immune privilege" of the brain.}, Author = {Streit, W. J. and Graeber, M. B. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Neuroglia;Human;Neuroimmunomodulation;Not relevant;11 Glia;Antigen-Presenting Cells;Macrophages;review, tutorial;Animals;Brain;Humans;review;Axons}, Medline = {89154609}, Nlm_Id = {8806785}, Number = {5}, Organization = {Department of Neuromorphology, Max Planck Institute of Psychiatry, Martinsried, Federal Republic of Germany.}, Pages = {301-7}, Pubmed = {2976393}, Title = {Functional plasticity of microglia: a review}, Uuid = {543D5E72-FB86-4332-A76B-AA39BA9B0DA5}, Volume = {1}, Year = {1988}} @article{Streit:1993, Abstract = {We reflect here on the development of a neuroimmunological concept which has been formulated over the past 5 years through studying microglial cell responses in the facial nerve system. A simple axotomy of the adult rat facial nerve which causes regeneration of facial motor neurons and little, if any, cell death can activate microglial cells just as easily as a full-blown degeneration of the entire nucleus induced by toxic ricin. In both instances, the prompt microglial reaction is characterized by a series of structural and phenotypic changes which are in many ways similar to an immune response, e.g., there is cell proliferation and upregulation of MHC antigens. However, since white blood cells do not participate in the retrograde response of facial motor neurons, we have adopted a notion which views microglia as a CNS-wide network of immunocompetent cells whose morphological dissimilarities from leukocytes are a result of their unique adaptation to the CNS architecture. We have continued our in vivo investigations of the phagocytic and immunophenotypic properties of microglial and perivascular cells during the retrograde reaction of facial motor neurons by using intra-neural injections of fluorogold (FG) and ricin followed by lectin and immunostaining for microglia. Two new findings can be added to the microglial neuroimmune network: (1) Microglia take up FG only after motor neuron degeneration, whereas perivascular cells may take up FG under nondegenerating conditions. (2) Immunologically important molecules, such as MHC class II, CD4, and leukocyte common antigens, are expressed by different microglial subpopulations. Thus there is functional and phenotypic heterogeneity among immunocompetent cells of the CNS.}, Author = {Streit, W. J. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Neuroglia;Facial Nerve;Antigens;Lectins;Not relevant;Denervation;Plant Lectins;11 Glia;review, tutorial;Blood Vessels;Injections;Animals;review;Axons}, Medline = {93138746}, Month = {1}, Nlm_Id = {8806785}, Number = {1}, Organization = {Department of Neuroscience, University of Florida, Gainesville 32610.}, Pages = {68-74}, Pubmed = {8423064}, Title = {Heterogeneity of microglial and perivascular cell populations: insights gained from the facial nucleus paradigm}, Uuid = {9B7A7571-3081-45D7-B136-90667365E8FD}, Volume = {7}, Year = {1993}} @article{Streit:2002a, Abstract = {The role of glial cells is to support and sustain proper neuronal function and microglia are no exception to this. This viewpoint article emphasizes the fundamental interdependence of microglia and neurons and takes a look at the possibility of what could happen if microglial cells became dysfunctional as a result of aging, genetics, or epigenetics. Could microglial senescence be a factor in the pathogenesis of Alzheimer's and other neurodegenerative diseases? The cautious answer to that question is 'yes'. Future studies along these lines may provide novel insights into microglial involvement in neurodegenerative disease pathogenesis.}, Author = {Streit, Wolfgang J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Endothelium, Vascular;Neuroglia;Central Nervous System;Interleukins;Endocrine System;Cytokines;Human;Signal Transduction;Not relevant;Chemokines;11 Glia;Microglia;review, tutorial;Animals;review;Neurons}, Medline = {22267059}, Month = {11}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, Florida 32611, USA. streit\@mbi.ufl.edu}, Pages = {133-9}, Pubmed = {12379901}, Title = {Microglia as neuroprotective, immunocompetent cells of the CNS}, Uuid = {852A2CEC-B241-44B3-B5BC-6675C54FD470}, Volume = {40}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10154}} @article{Streit:2004a, Abstract = {We have studied microglial morphology in the human cerebral cortex of two nondemented subjects using high-resolution LN-3 immunohistochemistry. Several abnormalities in microglial cytoplasmic structure, including deramification, spheroid formation, gnarling, and fragmentation of processes, were identified. These changes were determined to be different from the morphological changes that occur during microglial activation and they were designated collectively as microglial dystrophy. Quantitative evaluation of dystrophic changes in microglia revealed that these were much more prevalent in the older subject (68-year-old) than in the younger one (38-year-old). Thus, we conclude that microglial dystrophy is a sign of microglial cell senescence. We hypothesize that microglial senescence could be important for understanding age-related declines in cognitive function.}, Author = {Streit, Wolfgang J. and Sammons, Nicole W. and Kuhns, Amanda J. and Sparks, D. Larry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Aging;Cognition Disorders;Aged;Adult;Immunohistochemistry;Cell Aging;Human;Not relevant;Biological Markers;Atrophy;11 Glia;Microglia;Oligosaccharides;Male;Cerebral Cortex}, Month = {1}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Neuroscience, PO Box 100244, University of Florida College of Medicine, Building 59, 100 Newell Drive, Gainesville, FL 32610, USA. streit\@mbi.ufl.edu}, Pages = {208-12}, Pubmed = {14730714}, Title = {Dystrophic microglia in the aging human brain}, Uuid = {4B6FD6C0-C06C-4DBE-A3ED-FD1A1F4015BE}, Volume = {45}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10319}} @article{Streit:1993a, Abstract = {The question of whether activated microglial cells are potentially harmful or beneficial to injured central nervous system neurons is being addressed by examining in vivo and in vitro findings. While observations made in vivo suggest that microglial activation is triggered by injured neurons and may aid in regeneration, in vitro data show production of neurotoxic agents by cultured microglia. An effort is made to find a common denominator in these apparently conflicting findings by discussing microglial activation during motor neuron regeneration and during delayed neuronal death occurring as a consequence of global forebrain ischemia.}, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0891-0618}, Journal = {J Chem Neuroanat}, Keywords = {Cell Communication;Hippocampus;Models, Neurological;Get paper from library;11 Glia;Microglia;review, tutorial;Spinal Cord;Cells, Cultured;Brain;Animals;Neurons;review}, Medline = {94000514}, Nlm_Id = {8902615}, Number = {4}, Organization = {Department of Neuroscience, University of Florida, Gainesville 32610.}, Pages = {261-6}, Pubmed = {8397924}, Title = {Microglial-neuronal interactions}, Uuid = {6A2FC7F4-983A-4EDD-8FB3-A8726C557A03}, Volume = {6}, Year = {1993}} @article{Streit:1988a, Abstract = {The injection of toxic lectin from Ricinus communis into the rat facial nerve resulted in suicide transport and rapid degeneration of facial motor neurons. The reaction of glial cells to neuronal death in comparison with nerve crush lesions was studied by using lectin-HRP conjugates derived from Griffonia simplicifolia for the selective staining of microglial cells at both light and electron microscopic levels. In addition, the proliferative activity of microglia was assessed by quantification of 3H-thymidine incorporation. The astrocytic response was evaluated by light microscopic immunocytochemistry for glial fibrillary acidic protein. In the degenerating facial nucleus local microglial cells responded by rapid proliferation and phagocytosis of neuronal debris. After nerve crush, no phagocytes were observed, but microglial proliferation and perineuronal satellitosis were prominent. The astrocytic expression of glial fibrillary acidic protein in response to nerve crush proceeded gradually over a period of several weeks after which it declined, contrasting with accelerated astrocytic hypertrophy and permanent glial scarring after neuronal degeneration. These results show that the expression of glial fibrillary acidic protein by fibrous astrocytes is intensified after lethal neuronal injury compared to sublethal insults. In the absence of any observations indicating participation of hematogenous elements, it is proposed that local microglial cells transform into brain macrophages.}, Author = {Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Ricin;Neuroglia;Facial Nerve;Nerve Degeneration;Motor Neurons;Rats;Not relevant;Cell Division;Cell Survival;11 Glia;Nerve Crush;Animals;Rats, Inbred Strains}, Medline = {88198671}, Month = {2}, Nlm_Id = {0406041}, Number = {2}, Organization = {Department of Neuromorphology, Max Planck Institute of Psychiatry, Martinsried n. Munich, Federal Republic of Germany.}, Pages = {248-63}, Pubmed = {3360987}, Title = {Response of endogenous glial cells to motor neuron degeneration induced by toxic ricin}, Uuid = {5FF02678-1890-4EB5-ACA3-043CA29F2F5A}, Volume = {268}, Year = {1988}} @article{Streit:1990, Abstract = {A simple method for the lectin histochemical visualization of rat microglial cells is described. Advantages include ease of fixation of brain tissue using paraformaldehyde, and rapidity of tissue processing by vibratome sectioning. Furthermore, in addition to providing good structural preservation, the method achieves improved lectin binding, resulting in complete labeling of all microglial cells and in superior visualization of cellular processes. The lectin histochemical technique for rat microglia has the potential to be adapted to any mammalian species, and should prove valuable for neuroscientists interested in studying this glial cell type.}, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0022-1554}, Journal = {J Histochem Cytochem}, Keywords = {Neuroglia;Rats;Lectins;Not relevant;11 Glia;Spinal Cord;Histocytochemistry;Male;Brain;Rats, Inbred Strains;Animals}, Medline = {91010649}, Month = {11}, Nlm_Id = {9815334}, Number = {11}, Organization = {Department of Neuroscience, University of Florida College of Medicine, Gainesville 32610.}, Pages = {1683-6}, Pubmed = {2212623}, Title = {An improved staining method for rat microglial cells using the lectin from Griffonia simplicifolia (GSA I-B4)}, Uuid = {491054E2-FCDC-4E58-8615-31F149C99443}, Volume = {38}, Year = {1990}} @article{Streit:1997, Abstract = {Activated microglial cells are concentrated in senile plaques characteristic of Alzheimer's disease. Such accumulations of activated microglia may contribute towards neurodegeneration via production of cytokines and free radicals. Studies suggesting a link between Alzheimer's disease and heart disease led us to study microglia immunohistochemically, using monoclonal antibody LN-3, in age-matched nondemented humans with and without heart disease. Using a qualitative staging system for assessing morphological changes occurring in microglia, we found higher microglial activation in the brains of subjects with heart disease than in those without it. Lectin histochemical examination of brains from rabbits maintained on a high-cholesterol diet also revealed increased microglial activation and leukocyte infiltration. Collectively our observations from humans and rabbits suggest that hypercholesterolemia and heart disease accelerate brain aging, and that the formation of senile plaques may be the end result of progressive microglial activation that occurs with aging.}, Author = {Streit, W. J. and Sparks, D. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0946-2716}, Journal = {J Mol Med}, Keywords = {Aging;Aged;Human;Immunohistochemistry;Heart Diseases;Not relevant;Alzheimer Disease;Hypercholesterolemia;Middle Aged;Rabbits;Microglia;Animals;Brain;11 Glia}, Medline = {97237452}, Month = {2}, Nlm_Id = {9504370}, Number = {2}, Organization = {Department of Neuroscience, University of Florida Brain Institute, Gainesville 32610-0244, USA.}, Pages = {130-8}, Pubmed = {9083930}, Title = {Activation of microglia in the brains of humans with heart disease and hypercholesterolemic rabbits}, Uuid = {0A5C01E1-FB37-4E55-8863-45A05944D8EB}, Volume = {75}, Year = {1997}} @article{Streit:1987, Abstract = {Conjugates of the B4 isolectin from Griffonia simplicifolia seeds and horseradish peroxidase were used as a histochemical reagent for the specific visualization of microglial cells in the rat CNS. Resident microglia bearing galactose-containing glycoconjugates were stained throughout the brainstem and cerebellum. In the first week following axotomy of the facial nerve, a profound and rapid accumulation of reactive microglia, as evidenced by increasing lectin reactivity, was seen to take place in the facial nucleus. Light microscopy of paraffin sections demonstrated binding of lectin-horseradish peroxidase conjugates to microglial cytoplasmic processes. When ultrastructural cytochemistry was performed, reaction product was found localized on microglial plasma membranes, as well as on intracytoplasmic membranes. The glial reaction to axotomy was studied further with double labelling of microglia and astrocytes by lectin histochemistry and immunostaining for glial fibrillary acidic protein, respectively. Our results demonstrated the presence of membrane-associated glycoconjugates containing terminal alpha-D-galactose residues on microglia, but not on other glial cell types. The possible nature and function of these glycoconjugates are discussed.}, Author = {Streit, W. J. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {G;Brain Stem;Neuroglia;Binding Sites;Carbohydrates;Rats;Microscopy, Electron;Lectins;Not relevant;11 Glia;Histocytochemistry;Animals;Male;Horseradish Peroxidase;Rats, Inbred Strains;Support, Non-U.S. Gov't}, Medline = {87310543}, Month = {4}, Nlm_Id = {0364620}, Number = {2}, Pages = {249-60}, Pubmed = {3625239}, Title = {Lectin binding by resting and reactive microglia}, Uuid = {FAC8D6E0-E092-11DA-9DD9-000D9346EC2A}, Volume = {16}, Year = {1987}} @article{Streit:1989a, Abstract = {Proliferation of central nervous system (CNS) glia in response to peripheral nerve injury occurs without apparent participation of cells of the immune system. It is shown here that following transection of the rat facial nerve there is strongly elevated expression of class I, and to a lesser extent, class II antigens of the major histocompatibility complex (MHC) in the facial nucleus. It is demonstrated by double-immunofluorescence studies that the cells responsible for increased levels of MHC class I antigens are endogenous brain microglia. These findings emphasize the thought that microglia are immunocompetent cells, but, at the same time, raise the possibility for a non-immunological function of MHC antigens under conditions of neural regeneration.}, Author = {Streit, W. J. and Graeber, M. B. and Kreutzberg, G. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Neuroglia;Facial Nerve;Immunohistochemistry;Histocompatibility Antigens Class II;Rats;Not relevant;Biological Markers;11 Glia;Histocompatibility Antigens Class I;Animals;Male;Brain;Rats, Inbred Strains}, Medline = {89109521}, Month = {2}, Nlm_Id = {8109498}, Number = {2-3}, Organization = {Department of Neuromorphology, Max Planck Institute of Psychiatry, Martinsried, F.R.G.}, Pages = {117-23}, Pubmed = {2913044}, Title = {Peripheral nerve lesion produces increased levels of major histocompatibility complex antigens in the central nervous system}, Uuid = {3CE2FC37-F898-482D-A7FB-29412A6B15AB}, Volume = {21}, Year = {1989}} @article{Streit:2004, Abstract = {Microglia make up the innate immune system of the central nervous system and are key cellular mediators of neuroinflammatory processes. Their role in central nervous system diseases, including infections, is discussed in terms of a participation in both acute and chronic neuroinflammatory responses. Specific reference is made also to their involvement in Alzheimer's disease where microglial cell activation is thought to be critically important in the neurodegenerative process.}, Author = {Streit, and Mrak, and Griffin,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1742-2094}, Journal = {J Neuroinflammation}, Keywords = {Not relevant;11 Glia}, Month = {7}, Nlm_Id = {101222974}, Number = {1}, Organization = {Department of Neuroscience, University of Florida College of Medicine, P,O, Box 100244, Gainesville, Florida 32610, USA. streit\@mbi.ufl.edu}, Pages = {14}, Pii = {1742-2094-1-14}, Pubmed = {15285801}, Title = {Microglia and neuroinflammation: a pathological perspective}, Uuid = {1FD141C6-DC56-4E2C-911A-E37542B17397}, Volume = {1}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1742-2094-1-14}} @article{Streit:2000, Abstract = {Using reverse transcription polymerase chain reaction (RT-PCR), we have studied the temporal expression of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-beta 1), and tumor necrosis factor-alpha (TNF-alpha) mRNAs in three axotomy paradigms with distinct functional outcomes. Axotomy of adult rat facial motoneurons results in neuronal regeneration, axotomy of neonatal facial motoneurons results in neuronal apoptosis, and axotomy of rubrospinal neurons results in neuronal atrophy. Our RT-PCR findings show that a significant and sustained upregulation of IL-6 mRNA is associated uniquely with the regeneration of adult facial motoneurons. Histochemical studies using IL-6 immunohistochemistry show intense IL-6 immunoreactivity in axotomized adult facial motoneurons. Assessment of reactive glial changes with astroglial and microglial markers reveals that the reactive gliosis following adult facial nerve axotomy is more intense than that observed in either of the other two paradigms. Exposure of cultured microglial cells to IL-6 stimulates microglial proliferation in a dose-dependent manner. Cultured microglia also show expression of IL-6 receptor mRNA, as determined by RT-PCR. Our findings support the idea that reactive gliosis is required for neuron regeneration to occur, and more specifically, they suggest that neuron-derived IL-6 serves as a signalling molecule that induces microglial proliferation during motoneuron regeneration.}, Author = {Streit, W. J. and Hurley, S. D. and McGraw, T. S. and Semple-Rowland, S. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Tumor Necrosis Factor;Nerve Degeneration;Signal Transduction;Animals;Rats;Transforming Growth Factor beta;Comparative Study;Microglia;Female;Cell Communication;Rats, Wistar;Not relevant;11 Glia;RNA, Messenger;Male;Nerve Regeneration;Receptors, Interleukin-6;Support, Non-U.S. Gov't;Neurons;Axotomy;Interleukin-1;Support, U.S. Gov't, P.H.S.;Gliosis;Age Factors;Cell Division;Interleukin-6;Facial Nerve;Lectins;Gene Expression}, Medline = {20321007}, Month = {7}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Neuroscience, University of Florida College of Medicine and Brain Institute, Gainesville 32611, Florida, USA. streit\@ufbi.ufl.edu}, Pages = {10-20}, Pii = {10.1002/1097-4547(20000701)61:1<10::AID-JNR2>3.0.CO;2-E}, Pubmed = {10861795}, Title = {Comparative evaluation of cytokine profiles and reactive gliosis supports a critical role for interleukin-6 in neuron-glia signaling during regeneration}, Uuid = {43892833-7542-4488-B497-5E8ED2645EE5}, Volume = {61}, Year = {2000}} @article{Streit:2004b, Abstract = {The most visible and, until very recently, the only hypothesis regarding the involvement of microglial cells in Alzheimer's disease (AD) pathogenesis is centered around the notion that activated microglia are neurotoxin-producing immune effector cells actively involved in causing the neurodegeneration that is the cause for AD dementia. The concept of detrimental neuroinflammation has gained a strong foothold in the AD arena and is being expanded to other neurodegenerative diseases. This review takes a comprehensive and critical look at the overall evidence supporting the neuroinflammation hypothesis and points out some weaknesses. The current work also reviews evidence for an alternative theory, the microglial dysfunction hypothesis, which, although eliminating some of the shortcomings, does not necessarily negate the amyloid/neuroinflammation theory. The microglial dysfunction theory offers a different perspective on the identity of activated microglia and their role in AD pathogenesis taking into account the most recent insights gained from studying basic microglial biology.}, Author = {Streit, Wolfgang J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Amyloid beta-Protein;Encephalitis;Neurofibrillary Tangles;Cell Aging;Human;Neurotoxins;Models, Neurological;Gliosis;Alzheimer Disease;Microglia;review, tutorial;11 Glia;Not relevant;Animals;review}, Month = {7}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Neuroscience, University of Florida College of Medicine, Gainesville, Florida 32610-0244, USA. streit\@mbi.ufl.edu}, Pages = {1-8}, Pubmed = {15197750}, Title = {Microglia and Alzheimer's disease pathogenesis}, Uuid = {F13FB3E2-F91B-4EF5-82FC-A6FAD9F0BA31}, Volume = {77}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20093}} @article{Streit:2001, Abstract = {In recent years, increasing attention has been focused on chemokines as inflammatory mediators in the CNS. The limited number of studies that have investigated chemokine and chemokine receptor expression in Alzheimer's disease (AD) brain and in cell culture models seem to support a role for inflammation in AD pathogenesis. Here we provide a review of these studies, but in addition, point out the possible role of chemokines as communication molecules between neurons and microglia. Understanding neuron-microglia interactions is essential for understanding AD pathogenesis, and disturbances in chemokine-mediated intercellular communication may contribute toward a generalized impairment of microglial cell function.}, Author = {Streit, W. J. and Conde, J. R. and Harrison, J. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0197-4580}, Journal = {Neurobiol Aging}, Keywords = {Human;Not relevant;Chemokines;Alzheimer Disease;Microglia;review, tutorial;11 Glia;Brain Chemistry;review}, Medline = {21630088}, Nlm_Id = {8100437}, Number = {6}, Organization = {Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville, FL 32611, USA. streit\@ufbi.ufl.edu}, Pages = {909-13}, Pii = {S0197458001002901}, Pubmed = {11754998}, Title = {Chemokines and Alzheimer's disease}, Uuid = {046ADE1C-B3DB-440C-A352-AFA227CB3A04}, Volume = {22}, Year = {2001}} @article{Streit:1994a, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Glioma;Rats;Human;Phenotype;Not relevant;11 Glia;Microglia;Transforming Growth Factor beta;Brain Neoplasms;Animals;Immunity, Cellular;Major Histocompatibility Complex}, Medline = {94352547}, Month = {4}, Nlm_Id = {7609829}, Number = {2}, Organization = {Department of Neuroscience, University of Florida, Gainesville 32610.}, Pages = {205-6}, Pubmed = {8072665}, Title = {Cellular immune response in brain tumors}, Uuid = {6B8518E3-6DF8-4BC3-93EA-D67BCA55BCB9}, Volume = {20}, Year = {1994}} @article{Streit:1992, Abstract = {Delayed neuronal death induced by transient forebrain ischemia in the rat hippocampus is preceded by a prominent microglial reaction which begins within minutes after the ischemic injury. In the present study we have examined the effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on microglial activation and neuronal survival. Using lectin histochemistry to detect microglia, we show that the systemic administration of MK-801 prior to ischemia prevents microglial activation, as well as delayed death of CA1 pyramidal neurons. The results demonstrate that early blockage of the glutamate cascade prevents microglial activation, and could suggest a role for microglia in mediating ischemic injury.}, Author = {Streit, W. J. and Morioka, T. and Kalehua, A. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Hippocampus;Rats;Female;Not relevant;11 Glia;Mesoderm;Prosencephalon;Receptors, N-Methyl-D-Aspartate;Animals;Rats, Inbred Strains;Ischemic Attack, Transient;Dizocilpine Maleate}, Medline = {92322929}, Month = {2}, Nlm_Id = {9100935}, Number = {2}, Organization = {Department of Neuroscience, University of Florida, Gainesville 32610.}, Pages = {146-8}, Pubmed = {1535800}, Title = {MK-801 prevents microglial reaction in rat hippocampus after forebrain ischemia}, Uuid = {D99BF86D-75DC-4B65-8D0F-941426FF8120}, Volume = {3}, Year = {1992}} @article{Streit:1996, Abstract = {Microglial cells are exquisitely sensitive to neuronal damage. Neurons which have been damaged by an injury or a neurotoxicant will stimulate microglia in their immediate vicinity to become activated and undergo a series of morphologic and phenotypic changes. The changes occurring on microglial cells can be documented quite readily using histochemical methods, and it is suggested that the histological demonstration of microglial activation can serve as a very sensitive biological marker for neuron damage. While the functional significance of microglial activation is unknown, there is evidence to suggest that microglia may exert both neurotrophic and neurotoxic effects. However, proving that these functions are indeed carried out by microglia in vivo remains a formidable challenge for future investigations.}, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0161-813X}, Journal = {Neurotoxicology}, Keywords = {Nerve Degeneration;Not relevant;11 Glia;Microglia;review, tutorial;Animals;Brain Injuries;review}, Medline = {97241088}, Nlm_Id = {7905589}, Number = {3-4}, Organization = {Department of Neuroscience, University of Florida, Gainesville 32610, USA.}, Pages = {671-8}, Pubmed = {9086488}, Title = {The role of microglia in brain injury}, Uuid = {97F8632E-714B-4C9F-9E91-4C0DC0D80BCA}, Volume = {17}, Year = {1996}} @article{Streit:2001a, Abstract = {An understanding of microglial functions during normal CNS development is prerequisite for understanding developmental neurotoxicology. This review provides a brief summary of previous work regarding the origin of microglia and addresses differences and similarities between microglia and brain macrophages. Current concepts and ideas which implicate microglia in diverse developmental processes, such as apoptosis, axon growth, and vasculogenesis are discussed. The study of reactive microgliosis may prove useful in the histopathological analysis of neurotoxicant-induced brain damage during development.}, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0161-813X}, Journal = {Neurotoxicology}, Keywords = {Central Nervous System;Comparative Study;Human;Not relevant;11 Glia;Microglia;Macrophages;review, tutorial;Animals;review}, Medline = {21626810}, Month = {10}, Nlm_Id = {7905589}, Number = {5}, Organization = {Department of Neuroscience, University of Florida College of Medicine and McKnight Brain Institute, Gainesville 32611, USA. streit\@ufbi.ufl.edu}, Pages = {619-24}, Pubmed = {11770883}, Title = {Microglia and macrophages in the developing CNS}, Uuid = {D100E2D1-37E7-43DD-8014-D27C2C6C4316}, Volume = {22}, Year = {2001}} @article{Streit:1996a, Author = {Streit, W. J. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0079-6336}, Journal = {Prog Histochem Cytochem}, Keywords = {Aging;Adult;Human;Infection;Regeneration;Not relevant;11 Glia;Microglia;review, tutorial;Humans;Animals;Central Nervous System Diseases;review}, Medline = {97048470}, Nlm_Id = {0253725}, Number = {1}, Organization = {Department of Neuroscience, University of Florida Brain Institute Gainesville 32610, USA.}, Pages = {1-89}, Pubmed = {8893306}, Title = {Microglia: a pictorial}, Uuid = {A7A07CDA-C1F9-4FEE-892B-30F7483D9929}, Volume = {31}, Year = {1996}} @article{Streit:1999, Abstract = {Damage to the central nervous system (CNS) elicits the activation of both astrocytes and microglia. This review is focused on the principal features that characterize the activation of microglia after CNS injury. It provides a critical discussion of concepts regarding microglial biology that include the relationship between microglia and macrophages, as well as the role of microglia as immunocompetent cells of the CNS. Mechanistic and functional aspects of microgliosis are discussed primarily in the context of microglial neuronal interactions. The controversial issue of whether reactive microgliosis is a beneficial or a harmful process is addressed, and a resolution of this dilemma is offered by suggesting different interpretations of the term 'activated microglia' depending on its usage during in vivo or in vitro experimentation.}, Author = {Streit, W. J. and Walter, S. A. and Pennell, N. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0301-0082}, Journal = {Prog Neurobiol}, Keywords = {Neurons;Cell Communication;review, academic;Human;Gliosis;Not relevant;11 Glia;Microglia;Animals;review;Immunocompetence}, Medline = {99236971}, Month = {4}, Nlm_Id = {0370121}, Number = {6}, Organization = {Department of Neuroscience, University of Florida College of Medicine and Brain Institute, Gainesville 32610, USA. streit\@ufbi.ufl.edu}, Pages = {563-81}, Pii = {S0301008298000690}, Pubmed = {10221782}, Title = {Reactive microgliosis}, Uuid = {108CE8D3-7786-4625-89D3-97E8B0B9BA1F}, Volume = {57}, Year = {1999}} @article{Streit:1995, Author = {Streit, W. J. and Kincaid-Colton, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0036-8733}, Journal = {Sci Am}, Keywords = {Cytokines;Human;AIDS Dementia Complex;Immunity;Not relevant;Alzheimer Disease;Microglia;Down Syndrome;review, tutorial;11 Glia;Brain;review}, Medline = {97113064}, Month = {11}, Nlm_Id = {0404400}, Number = {5}, Organization = {University of Florida Brain Institute, USA.}, Pages = {54-5, 58-61}, Pubmed = {8966536}, Title = {The brain's immune system}, Uuid = {2181400D-779F-406C-8A16-03258FF63EAE}, Volume = {273}, Year = {1995}} @article{Streit:2000a, Abstract = {In addition to astrocytes and oligodendrocytes, microglia represent the third major population of glial cells within the central nervous system (CNS). Microglia are distributed ubiquitously throughout the brain and spinal cord, and one of their main functions is to monitor and sustain neuronal health. Microglial cells are quite sensitive to even minor disturbances in CNS homeostasis, and they become readily activated during most neuropathologic conditions, including peripheral nerve injury, trauma and stroke, inflammatory disease, and neurotoxicant-induced neuronal injury. During activation, microglia display conspicuous functional plasticity, which involves changes in cell morphology, cell number, cell surface receptor expression, and production of growth factors and cytokines. The many changes occurring in activated cells reflect the altered functional states of microglia that are induced by signals arising from injured neurons. Thus, neuronal-microglial signaling plays a fundamental role in understanding how the CNS responds to injury. Reactive microgliosis should be viewed as a cellular effort to initiate ameliorative and reparative measures in the injured brain.}, Author = {Streit, W. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0192-6233}, Journal = {Toxicol Pathol}, Keywords = {Human;Gliosis;Not relevant;11 Glia;Microglia;review, tutorial;Animals;Brain Injuries;review}, Medline = {20132471}, Nlm_Id = {7905907}, Number = {1}, Organization = {Department of Neuroscience, University of Florida College of Medicine and Brain Institute, Gainesville 32610-0244, USA. streit\@ufbi.ufl.edu}, Pages = {28-30}, Pubmed = {10668987}, Title = {Microglial response to brain injury: a brief synopsis}, Uuid = {3C6F6228-8000-4D04-9959-A7C6D499306C}, Volume = {28}, Year = {2000}} @article{Strizki:1997, Abstract = {We used a monoclonal antibody (12G5) directed against an extracellular domain of CXCR-4 to investigate the role of this receptor in infection of immortalized lymphoid cell lines, peripheral blood mononuclear cells (PBMCs), and primary brain microglia with a dual-tropic strain of human immunodeficiency virus (HIV-1(89.6)) and a T-tropic strain (HIV-1(IIIB)). Addition of antibody 12G5 to cells prior to and during infection with HIV-1(89.6) inhibited p24 production 100- to 10,000-fold in CEMx174 and 174-CD4 cells and about 10-fold in PBMC cultures but had no activity against infection of either monocyte-derived macrophages or brain microglia. In contrast, 12G5 had little or no effect on infection of CEMx174 cells with HIV-1(IIIB) or HIV-1(HxB). To identify the region of the HIV-1(89.6) envelope that confers sensitivity to 12G5, we used chimeric molecular clones. Chimeras containing the V3 loop region of HIV-1(89.6) were inhibited by 12G5 to the same degree as wild-type HIV-1(89.6) whereas replication of those viruses containing the V3 loop of HIV-1(HxB) was not inhibited by the antibody. A similar pattern was seen in infections of a U87 glioblastoma line that coexpresses CD4 and CXCR-4. Antibody 12G5 was also able to block fusion between HeLa-CD4 cells and CEMx174 cells chronically infected with HIV-1(89.6) but had no effect on fusion mediated by cells chronically infected with HIV-1(IIIB). Taken together, these results suggest that different strains of HIV-1 may interact with different sites on CXCR-4 or may have different binding affinities for the coreceptor.}, Author = {Strizki, J. M. and Turner, J. D. and Collman, R. G. and Hoxie, J. and Gonz{\'a}lez-Scarano, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {T-Lymphocytes;Receptors, CXCR4;HIV-1;Humans;Cells, Cultured;Microglia;Receptors, HIV;Cell Fusion;Antigens, CD4;11 Glia;Hela Cells;Cell Line;Research Support, U.S. Gov't, P.H.S.;Peptide Fragments;Antibodies, Monoclonal;Tumor Cells, Cultured;HIV Core Protein p24;Membrane Proteins;HIV Envelope Protein gp120}, Medline = {97332414}, Month = {7}, Nlm_Id = {0113724}, Number = {7}, Organization = {Department of Neurology and Microbiology, University of Pennsylvania Medical Center, Philadelphia 19104-6146, USA.}, Pages = {5678-83}, Pubmed = {9188648}, Title = {A monoclonal antibody (12G5) directed against CXCR-4 inhibits infection with the dual-tropic human immunodeficiency virus type 1 isolate HIV-1(89.6) but not the T-tropic isolate HIV-1(HxB)}, Uuid = {319AEF9D-2CC3-4CBF-AF69-FB2E41571557}, Volume = {71}, Year = {1997}} @article{Strogatz:2001, Abstract = {The study of networks pervades all of science, from neurobiology to statistical physics. The most basic issues are structural: how does one characterize the wiring diagram of a food web or the Internet or the metabolic network of the bacterium Escherichia coli? Are there any unifying principles underlying their topology? From the perspective of nonlinear dynamics, we would also like to understand how an enormous network of interacting dynamical systems-be they neurons, power stations or lasers-will behave collectively, given their individual dynamics and coupling architecture. Researchers are only now beginning to unravel the structure and dynamics of complex networks.}, Author = {Strogatz, S. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {20 Networks;Systems Theory;research support, non-u.s. gov't;research support, u.s. gov't, non-p.h.s.;Models, Theoretical;24 Pubmed search results 2008;review}, Month = {3}, Nlm_Id = {0410462}, Number = {6825}, Organization = {Department of Theoretical and Applied Mechanics and Center for Applied Mathematics, Cornell University, Ithaca, New York 14853-1503, USA. strogatz\@cornell.edu}, Pages = {268-76}, Pubmed = {11258382}, Title = {Exploring complex networks}, Uuid = {292E1D50-5510-43BE-8482-14F180B2E0AF}, Volume = {410}, Year = {2001}, url = {papers/Strogatz_Nature2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35065725}} @article{Struble:2001, Abstract = {Olfactory receptor neurons can regenerate from basal stem cells. Receptor neuron lesion causes degenerative changes in the olfactory bulb followed by regeneration as new olfactory receptor axons innervate the olfactory bulb. To our knowledge, parametric analyses of morphometric changes in the olfactory bulb during degeneration and regeneration do not exist except in abstract form. To better characterize olfactory bulb response, we performed morphometric analysis in rats following reversible olfactory nerve lesion with diethyldithiocarbamate. We also performed anterograde tracing of the olfactory nerve with wheatgerm agglutinin linked to horseradish peroxidase. Results of morphometry and tracing were complementary. The glomerular layer and external plexiform layer showed shrinkage of 45 and 26\%, respectively, at 9 days. No significant shrinkage occurred in any other layer. Individual glomeruli shrank by 40-50\%at 3 and 9 days following lesion. These data show that degenerative changes occur both in the glomeruli and transneuronally in the external plexiform layer. Olfactory nerve regeneration (identified by WGA-HRP transport) paralleled volumetric recovery. Recovery occurred first in ventral and lateral glomeruli between 9 and 16 days followed by recovery in medial and dorsal glomeruli. These data indicate substantial transynaptic degeneration in the olfactory bulb and a heretofore unrecognized gradient in olfactory nerve regeneration that can be used to systematically study recovery of a cortical structure.}, Author = {Struble, R. G. and Beckman, S. L. and Fesser, E. and Nathan, B. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Chem Senses}, Keywords = {I pdf;13 Olfactory bulb anatomy}, Number = {8}, Organization = {Center for Alzheimer Disease and Related Disorders, PO Box 19682, Southern Illinois University School of Medicine, Springfield, IL 62794, USA. Department of Biological Sciences, Eastern Illinois University, Charleston, IL 61920, USA.}, Pages = {971-81.}, Title = {Volumetric and horseradish peroxidase tracing analysis of rat olfactory bulb following reversible olfactory nerve lesions}, Uuid = {CDCE0028-60A1-4399-B30D-40B5C894ADC2}, Volume = {26}, Year = {2001}, url = {papers/Struble_ChemSenses2001}} @article{Stuart:1997, Abstract = {1. Initiation and propagation of action potentials evoked by extracellular synaptic stimulation was studied using simultaneous dual and triple patch pipette recordings from different locations on neocortical layer 5 pyramidal neurons in brain slices from 4-week-old rats (P26-30) at physiological temperatures. 2. Simultaneous cell-attached and whole-cell voltage recordings from the apical trunk (up to 700 microns distal to the soma) and the soma indicated that proximal synaptic stimulation (layer 4) initiated action potentials first at the soma, whereas distal stimulation (upper layer 2/3) could initiate dendritic regenerative potentials prior to somatic action potentials following stimulation at higher intensity. 3. Somatic action potentials, once initiated, propagated back into the apical dendrites in a decremented manner which was frequency dependent. The half-width of back propagating action potentials increased and their maximum rate of rise decreased with distance from the soma, with the peak of these action potentials propagating with a conduction velocity of approximately 0.5 m s-1. 4. Back-propagation of action potentials into the dendritic tree was associated with dendritic calcium electrogenesis, which was particularly prominent during bursts of somatic action potentials. 5. When dendritic regenerative potentials were evoked prior to somatic action potentials, the more distal the dendritic recording was made from the soma the longer the time between the onset of the dendritic regenerative potential relative to somatic action potential. This suggested that dendritic regenerative potentials were initiated in the distal apical dendrites, possibly in the apical tuft. 6. At any one stimulus intensity, the initiation of dendritic regenerative potentials prior to somatic action potentials could fluctuate, and was modulated by depolarizing somatic or hyperpolarizing dendritic current injection. 7. Dendritic regenerative potentials could be initiated prior to somatic action potentials by dendritic current injections used to simulate the membrane voltage change that occurs during an EPSP. Initiation of these dendritic potentials was not affected by cadmium (200 microM), but was blocked by TTX (1 microM). 8. Dendritic regenerative potentials in some experiments were initiated in isolated from somatic action potentials. The voltage change at the soma in response to these dendritic regenerative events was small and subthreshold, showing that dendritic regenerative events are strongly attenuated as they spread to the soma. 9. Simultaneous whole-cell recordings from the axon initial segment and the soma indicated that synaptic stimulation always initiated action potentials first in the axon. The further the axonal recording was made from the soma the greater the time delay between axonal and somatic action potentials, indicating a site of action potential initiation in the axon at least 30 microns distal to the soma. 10. Simultaneous whole-cell recordings from the apical dendrite, soma and axon initial segment showed that action potentials were always initiated in the axon prior to the soma, and with the same latency difference, independent of whether dendritic regenerative potentials were initiated or not. 11. It is concluded that both the apical dendrites and the axon of neocortical layer 5 pyramidal neurons in P26-30 animals are capable of initiating regenerative potentials. Regenerative potentials initiated in dendrites, however, are significantly attenuated as they spread to the soma and axon. As a consequence, action potentials are always initiated in the axon before the soma, even when synaptic activation is intense enough to initiate dendritic regenerative potentials. Once initiated, the axonal action potentials are conducted orthogradely into the axonal arbor and retrogradely into the dendritic tree.}, Author = {Stuart, G. and Schiller, J. and Sakmann, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Synapses;Electric Conductivity;Dendrites;Excitatory Postsynaptic Potentials;21 Neurophysiology;Action Potentials;Rats;in vitro ;research support, non-u.s. gov't ;Rats, Wistar;Neocortex;Pyramidal Cells;Animals;Patch-Clamp Techniques;24 Pubmed search results 2008;Axons}, Month = {12}, Nlm_Id = {0266262}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut f{\"u}r medizinische Forschung, Heidelberg, Germany. Greg.Stuart\@anu.edu.au}, Pages = {617-32}, Pubmed = {9457640}, Title = {Action potential initiation and propagation in rat neocortical pyramidal neurons}, Uuid = {15C45139-279F-4B86-8940-146253234D10}, Volume = {505 ( Pt 3)}, Year = {1997}} @article{Stuckmann:2001, Abstract = {To identify molecules involved in neurogenesis, we have raised monoclonal antibodies against embryonic day 12.5 mouse telencephalon. One antibody, monoclonal antibody 25H11, stains predominantly the ventricular zone of the anterior and lateral telencephalon. Purification of the 25H11 antigen, a 47 kDa integral membrane protein, from approximately 2500 mouse telencephali reveals its identity with ephrin B1. Ephrin B1 appears at the onset of neocortical neurogenesis, being first expressed in neuron-generating neuroepithelial cells and rapidly thereafter in virtually all neuroepithelial cells. Expression of ephrin B1 persists through the period of neocortical neurogenesis and is downregulated thereafter. Ephrin B1 is present on the ventricular as well as basolateral plasma membrane of neuroepithelial cells and exhibits an ventricular-high to pial-low gradient across the ventricular zone. Expression of ephrin B1 is also detected on radial glial cells, extending all the way to their pial endfeet, and on neurons in the mantle/intermediate zone but not in the cortical plate. Our results suggest that ephrin B1, presumably via ephrin-Eph receptor signaling, has a role in neurogenesis. Given the ventricular-to-pial gradient of ephrin B1 on the neuroepithelial cell surface and its known role in cell migration in other systems mediated by its repulsive properties, we propose that ephrin B1 may be involved in the migration of newborn neurons out from the ventricular zone toward the neocortex.}, Author = {Stuckmann, I. and Weigmann, A. and Shevchenko, A. and Mann, M. and Huttner, W. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurosci}, Keywords = {Neocortex/cytology/embryology/metabolism;Cell Membrane/metabolism;Neurons/cytology/*metabolism;Gene Expression Regulation, Developmental;Rats;Animal;Telencephalon/cytology/*embryology/*metabolism;Epithelial Cells/cytology/*metabolism;Support, Non-U.S. Gov't;Antibody Specificity;Mice, Inbred Strains;Membrane Proteins/*biosynthesis/chemistry/metabolism;Organ Specificity;C;Pia Mater/cytology/embryology/metabolism;04 Adult neurogenesis factors;Cell Movement/physiology;Mice;Morphogenesis/physiology;Antibodies, Monoclonal/isolation &purification/metabolism;Antigens, Differentiation/biosynthesis/chemistry/immunology;Molecular Weight;Cerebral Ventricles/cytology/embryology/metabolism;Signal Transduction/physiology;Neuroglia/cytology/metabolism}, Number = {8}, Organization = {Department of Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany.}, Pages = {2726-37.}, Title = {Ephrin B1 is expressed on neuroepithelial cells in correlation with neocortical neurogenesis}, Uuid = {7F029820-46DC-4CDC-A474-A3477D4792A8}, Volume = {21}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11306625%20http://www.jneurosci.org/cgi/content/full/21/8/2726%20http://www.jneurosci.org/cgi/content/abstract/21/8/2726}} @article{Studer:2000, Abstract = {Standard cell culture systems impose environmental oxygen (O(2)) levels of 20\%, whereas actual tissue O(2) levels in both developing and adult brain are an order of magnitude lower. To address whether proliferation and differentiation of CNS precursors in vitro are influenced by the O(2) environment, we analyzed embryonic day 12 rat mesencephalic precursor cells in traditional cultures with 20\%O(2) and in lowered O(2) (3 +/- 2\%). Proliferation was promoted and apoptosis was reduced when cells were grown in lowered O(2), yielding greater numbers of precursors. The differentiation of precursor cells into neurons with specific neurotransmitter phenotypes was also significantly altered. The percentage of neurons of dopaminergic phenotype increased to 56\%in lowered O(2) compared with 18\%in 20\%O(2). Together, the increases in total cell number and percentage of dopaminergic neurons resulted in a ninefold net increase in dopamine neuron yield. Differential gene expression analysis revealed more abundant messages for FGF8, engrailed-1, and erythropoietin in lowered O(2). Erythropoietin supplementation of 20\%O(2) cultures partially mimicked increased dopaminergic differentiation characteristic of CNS precursors cultured in lowered O(2). These data demonstrate increased proliferation, reduced cell death, and enhanced dopamine neuron generation in lowered O(2), making this method an important advance in the ex vivo generation of specific neurons for brain repair.}, Author = {Studer, L. and Csete, M. and Lee, S. H. and Kabbani, N. and Walikonis, J. and Wold, B. and McKay, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Survival;Cell Differentiation;Animals;Dopamine;Rats;Oxygen;Research Support, U.S. Gov't, Non-P.H.S.;Antigens, Differentiation;Apoptosis;Cell Hypoxia;23 Technique;Fibroblast Growth Factor 2;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;In Situ Nick-End Labeling;Cell Division;Central Nervous System;Bromodeoxyuridine;Stem Cells;Erythropoietin}, Medline = {20482307}, Month = {10}, Nlm_Id = {8102140}, Number = {19}, Organization = {Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.}, Pages = {7377-83}, Pubmed = {11007896}, Title = {Enhanced proliferation, survival, and dopaminergic differentiation of CNS precursors in lowered oxygen}, Uuid = {3031270F-5455-4E6C-A5C1-465BFFBC78BC}, Volume = {20}, Year = {2000}} @article{Stumm:2003, Abstract = {The chemotactic factors directing interneuron migration during cerebrocortical development are essentially unknown. Here we identify the CXC chemokine receptor 4 (CXCR4) in interneuron precursors migrating from the basal forebrain to the neocortex and demonstrate that stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for isolated striatal precursors. In addition, we show that CXCR4 is present in early generated Cajal-Retzius cells of the cortical marginal zone. In mice with a null mutation in CXCR4 or SDF-1, interneurons were severely underrepresented in the superficial layers and ectopically placed in the deep layers of the neocortex. In contrast, the submeningeal positioning of Cajal-Retzius cells was unaffected. Thus, our findings suggest that SDF-1, which is highly expressed in the embryonic leptomeninx, selectively regulates migration and layer-specific integration of CXCR4-expressing interneurons during neocortical development.}, Author = {Stumm, Ralf K. and Zhou, Chun and Ara, Toshiaki and Lazarini, Fran\c{c}oise and Dubois-Dalcq, Monique and Nagasawa, Takashi and H{\"o}llt, Volker and Schulz, Stefan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Receptors, CXCR4;Signal Transduction;Animals;Gene Expression Regulation, Developmental;Rats;Neocortex;Cell Count;Cell Movement;Cell Adhesion Molecules, Neuronal;Mice, Inbred C57BL;Rats, Wistar;Serine Endopeptidases;RNA, Messenger;In Situ Hybridization;Extracellular Matrix Proteins;Nervous System Malformations;Mice, Knockout;Chemokines, CXC;Mice;Interneurons;24 Pubmed search results 2008;Immunohistochemistry;Stem Cells;Nerve Tissue Proteins;Choristoma;Research Support, Non-U.S. Gov't}, Medline = {22716536}, Month = {6}, Nlm_Id = {8102140}, Number = {12}, Organization = {Department of Pharmacology and Toxicology, Otto-von-Guericke University, 39120 Magdeburg, Germany.}, Pages = {5123-30}, Pii = {23/12/5123}, Pubmed = {12832536}, Title = {CXCR4 regulates interneuron migration in the developing neocortex}, Uuid = {F892B6ED-E9CA-45B4-A3AD-977216D6CE59}, Volume = {23}, Year = {2003}} @article{Sturrock:1988, Abstract = {Macrophages were found in the meningeal sheath of the human optic nerve at all ages from 8 to 18 weeks post-conception. At 8 weeks the majority of macrophages contained few cytoplasmic organelles or vacuoles, but even at this age a small number of cells packed with small dense bodies were present. With increasing age the number of organelles increased and some vacuolated macrophages were present. The morphology of macrophages largely depended on the part of the meninges in which they were situated. Those lying in the subarachnoid space or loose outer layers of the dura were irregularly shaped and often vacuolated, whereas those lying in the tightly packed layer of arachnoid at its junction with the dura were elongated and contained few, if any, vacuoles. A few meningeal macrophages were observed apparently migrating along the fibrous septa which carry blood vessels into the substance of the nerve. The main structural differences between meningeal macrophages and optic nerve microglia (Sturrock, 1984) were the presence in the latter of numerous small vacuoles and long strands of endoplasmic reticulum. These structural differences may be the result of microglia being actively engaged in phagocytosis of the large number of degenerating axons which are present in the optic nerve between 8 and 10 weeks post-conception.}, Author = {Sturrock, R. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0021-8782}, Journal = {J Anat}, Keywords = {Gestational Age;Human;Microscopy, Electron;Meninges;Not relevant;11 Glia;Macrophages;Optic Nerve}, Medline = {89066390}, Month = {4}, Nlm_Id = {0137162}, Organization = {Department of Anatomy, University of Dundee, Scotland.}, Pages = {145-51}, Pubmed = {3198475}, Title = {An electron microscopic study of macrophages in the meninges of the human embryonic optic nerve}, Uuid = {BBC675A2-8700-456C-B970-45620D9DC789}, Volume = {157}, Year = {1988}} @article{Sudo:1998, Abstract = {Although microglial cells are well known to become activated in the pathological brain, mechanisms underlying the microglial activation are not fully understood. In the present study, with an aim to elucidate whether neurons are involved in the microglial activation, we compared the morphology and the superoxide anion (O2-)-generating activity of rat microglial cells in pure culture with those of cells cocultured with rat primary cortical neurons. Microglial cells in pure culture in serum-free Eagle's minimum essential medium on poly-L-lysine-coated coverslips displayed ramified morphology and suppressed activity of O2- generation. In contrast, microglial cells in neuron-microglia coculture under the same conditions as those for the pure culture displayed ameboid shape and upregulated activity of O2- generation. Electron microscopic observation revealed that microglial cells in coculture were more abundant in Golgi apparatus and secretory granules than those in pure culture and that some of microglial cells in the vicinity of neurites exhibited membrane specialization reminiscent of a junctional apparatus with high electron density between a microglial soma and a neurite. Microglial cells in coculture tended to tie neurites in bundles by extending processes. Medium conditioned by neurons significantly enhanced O2- generation by microglia, but microglial cells in contact with or in close apposition to cocultured neurons were much more intensely activated than those remote from the neurons. Furthermore, the membrane fraction of cortical neurons activated microglial cells, and this effect was abolished by treating the neuronal membrane with trypsin or neuraminidase. In conclusion, neuronal-microglial contact may be necessary to mediate microglial activation. The present findings suggest that the contact of microglia with damaged neurons in the brain is a plausible cause to activate microglia in the neuropathological processes.}, Author = {Sudo, S. and Tanaka, J. and Toku, K. and Desaki, J. and Matsuda, S. and Arai, T. and Sakanaka, M. and Maeda, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Neuraminidase;Animals;Astrocytes;Cells, Cultured;Serine;Rats;N-Acetylneuraminic Acid;Microglia;Cell Communication;Superoxides;Culture Media, Conditioned;Trypsin;11 Glia;Alpha;Animals, Newborn;Support, Non-U.S. Gov't;Tetradecanoylphorbol Acetate;Cerebral Cortex;Cell Size;Neurons;Carcinogens;Glycine;Anions;Cell Culture;Microscopy, Electron}, Medline = {99096824}, Month = {12}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Anesthesiology and Resuscitology, School of Medicine, Ehime University, Shigenobu, Ehime, 791-0295, Japan.}, Pages = {499-510}, Pii = {S0014488698969114}, Pubmed = {9878185}, Title = {Neurons induce the activation of microglial cells in vitro}, Uuid = {1BF1DD64-EE31-11DA-8605-000D9346EC2A}, Volume = {154}, Year = {1998}, url = {papers/Sudo_ExpNeurol1998.pdf}} @article{Sugama:2003, Abstract = {Dopaminergic neurons in the substantia nigra pars compacta undergo apoptosis after transection of the medial forebrain bundle. We have assessed the temporal and sequential activities of microglia in these events by examining the complement-3 (OX-42), major histocompatibility complex class II antigen presentation (OX-6) and phagocytic activity (ED1), and correlating these indicators with dopaminergic neuronal loss. Microglia in the ipsilateral substantia nigra pars reticulata evinced activation morphology at 12 h postaxotomy. Phagocytic microglia apposed dying dopaminergic neurons in the pars compacta starting at 3 days postlesion; their number increased through 14 days and slowly decreased. Nuclear chromatin condensation and significant loss of tyrosine hydroxylase-positive dopaminergic neurons occurred around 7 days postlesion. In contrast to microglial expression of interleukin-1beta and inducible nitric oxide synthase at the axotomy site, nigral microglia were interleukin-1beta and inducible nitric oxide synthase-negative. Consistently, RNase protection assays showed that interleukin-1beta and inducible nitric oxide synthase transcripts in nigra were equivocal. The present data support the idea that phagocytosis of axotomized neurons by activated microglia is not limited to dead neurons but includes dying neurons probably without cytotoxic effects of inflammatory substances, such as interleukin-1beta or nitric oxide.}, Author = {Sugama, S. and Cho, B. P. and Degiorgio, L. A. and Shimizu, Y. and Kim, S. S. and Kim, Y. S. and Shin, D. H. and Volpe, B. T. and Reis, D. J. and Cho, S. and Joh, T. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Nitric-Oxide Synthase;Substantia Nigra;Cytokines;Comparative Study;Rats;Apoptosis;Not relevant;Time Factors;Rats, Wistar;11 Glia;Microglia;Tyrosine 3-Monooxygenase;Animals;Male;Support, Non-U.S. Gov't;Medial Forebrain Bundle;Axotomy}, Medline = {22506139}, Nlm_Id = {7605074}, Number = {4}, Organization = {Laboratory of Molecular Neurobiology, The W M Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA.}, Pages = {925-33}, Pii = {S0306452202005729}, Pubmed = {12617934}, Title = {Temporal and sequential analysis of microglia in the substantia nigra following medial forebrain bundle axotomy in rat}, Uuid = {042AB9F4-4074-43EE-83CB-3015FC2AADA3}, Volume = {116}, Year = {2003}, url = {papers/Sugama_Neuroscience2003.pdf}} @article{Sugino:2006, Abstract = {Identifying the neuronal cell types that comprise the mammalian forebrain is a central unsolved problem in neuroscience. Global gene expression profiles offer a potentially unbiased way to assess functional relationships between neurons. Here, we carried out microarray analysis of 12 populations of neurons in the adult mouse forebrain. Five of these populations were chosen from cingulate cortex and included several subtypes of GABAergic interneurons and pyramidal neurons. The remaining seven were derived from the somatosensory cortex, hippocampus, amygdala and thalamus. Using these expression profiles, we were able to construct a taxonomic tree that reflected the expected major relationships between these populations, such as the distinction between cortical interneurons and projection neurons. The taxonomic tree indicated highly heterogeneous gene expression even within a single region. This dataset should be useful for the classification of unknown neuronal subtypes, the investigation of specifically expressed genes and the genetic manipulation of specific neuronal circuit elements.}, Author = {Sugino, Ken and Hempel, Chris M. and Miller, Mark N. and Hattox, Alexis M. and Shapiro, Peter and Wu, Caizi and Huang, Z. Josh and Nelson, Sacha B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Fluorescent Dyes;research support, n.i.h., extramural ;Electrophysiology;Animals;Bacterial Proteins;Oligonucleotide Array Sequence Analysis;Patch-Clamp Techniques;Mice, Transgenic;Green Fluorescent Proteins;Male;Reverse Transcriptase Polymerase Chain Reaction;Prosencephalon;In Situ Hybridization;Brain Chemistry;Neurons;21 Neurophysiology;Flow Cytometry;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Genes, Reporter;Luminescent Proteins;Gene Expression;Data Interpretation, Statistical;Immunohistochemistry}, Month = {1}, Nlm_Id = {9809671}, Number = {1}, Organization = {Department of Biology and National Center for Behavioral Genomics, Brandeis University, MS 008, 415 South Street, Waltham, Massachusetts 02454-9110, USA.}, Pages = {99-107}, Pii = {nn1618}, Pubmed = {16369481}, Title = {Molecular taxonomy of major neuronal classes in the adult mouse forebrain}, Uuid = {24DFF44D-C0A3-4D75-979D-6D0A0D6D4850}, Volume = {9}, Year = {2006}, url = {papers/Sugino_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1618}} @article{Sugiyama:2008, Abstract = {Neural circuits are shaped by experience in early postnatal life. Distinct GABAergic connections within visual cortex determine the timing of the critical period for rewiring ocular dominance to establish visual acuity. We find that maturation of the parvalbumin (PV)-cell network that controls plasticity onset is regulated by a selective re-expression of the embryonic Otx2 homeoprotein. Visual experience promoted the accumulation of non-cell-autonomous Otx2 in PV-cells, and cortical infusion of exogenous Otx2 accelerated both PV-cell development and critical period timing. Conversely, conditional removal of Otx2 from non-PV cells or from the visual pathway abolished plasticity. Thus, the experience-dependent transfer of a homeoprotein may establish the physiological milieu for postnatal plasticity of a neural circuit.}, Author = {Sugiyama, Sayaka and Di Nardo, Ariel A. and Aizawa, Shinichi and Matsuo, Isao and Volovitch, Michel and Prochiantz, Alain and Hensch, Takao K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {Visual Cortex;Sensory Deprivation;24 Pubmed search results 2008;research support, non-u.s. gov't;Neuronal Plasticity;Parvalbumins;Recombinant Proteins;Interneurons;Animals;Humans;Mice;Otx Transcription Factors;Visual Pathways}, Month = {8}, Nlm_Id = {0413066}, Number = {3}, Organization = {Lab for Neuronal Circuit Development, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.}, Pages = {508-20}, Pii = {S0092-8674(08)00839-8}, Pubmed = {18692473}, Title = {Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity}, Uuid = {08FFB5E3-B3F6-4EFE-9EC2-EB0FCC632D1E}, Volume = {134}, Year = {2008}, url = {papers/Sugiyama_Cell2008.pdf}, Bdsk-File-2 = {papers/Sugiyama_Cell2008a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.05.054}} @article{Sugiyama:1995, Abstract = {Multiple subpial transection (MST) is an effective surgical therapy for patients with intractable seizures whose epileptogenic lesions lie in the cortex and are unresectable. Morrell developed this procedure and reported clinical results obtained using it. However, only the disappearance of epileptiform discharges after MST in an experimental model of epilepsy has been demonstrated. The aim of this study was to establish the histological changes caused by MST and evaluate the effects of this procedure on interneuronal discharge spread in an epilepsy model, i.e. acute cortical kindling in rabbits. Histologically, vertical cracks in the transected cortex with mild gliosis and very little tissue disruption were observed. Horizontal fibers across the crack had been transected, whereas vertical fibers and neuronal cell bodies were preserved. The stimulation-induced after-discharges (ADs) were analyzed: cortical hyperactivity across the transected zone was reduced significantly earlier than that in the control group. Propagation of ADs induced by the kindling effect was also inhibited. These results suggest that MST interrupts not only neuronal synchronization, but also excitatory interneuronal conduction, in this epilepsy model.}, Author = {Sugiyama, S. and Fujii, M. and Ito, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {Epilepsy;Electric Stimulation;Electroencephalography;24 Pubmed search results 2008;21 Epilepsy;21 Neurophysiology;Female;Neural Conduction;Kindling (Neurology);Parietal Lobe;Electrophysiology;Interneurons;Animals;Male;Cerebral Cortex;Rabbits;Frontal Lobe}, Medline = {95369222}, Month = {5}, Nlm_Id = {8703089}, Number = {1}, Organization = {Department of Neurosurgery, Yamaguchi University School of Medicine, Japan.}, Pages = {1-9}, Pii = {092012119500003S}, Pubmed = {7641670}, Title = {The electrophysiological effects of multiple subpial transection (MST) in an experimental model of epilepsy induced by cortical stimulation}, Uuid = {03E256C4-A807-4DAF-A13E-BE86F08EC6BC}, Volume = {21}, Year = {1995}} @article{Suhonen:1996, Abstract = {Neurogenesis continues throughout adulthood in discrete regions. Proliferative zones include the subependymal zone, from where progenitors migrate along the rostral migratory pathway to differentiate into neurons in the olfactory bulb, and the hippocampal subgranular zone, where they migrate and differentiate into granule neurons. Progenitors isolated from adult subependymal zone exhibit in vitro neurogenesis when stimulated with epidermal or fibroblast growth factor. Cultured adult rat hippocampal progenitors (AHPs) grafted to adult rat hippocampus show site-specific neuronal differentiation. Here we investigate determinants of multipotentiality in the adult central nervous system, by grafting AHPs into homotypic (hippocampus) or heterotypic (the rostral migratory pathway) neurogenic sites or a heterotypic, non-neurogenic site (the cerebellum). We found that grafts into neurogenic, but not nonneurogenic sites, showed neuronal differentiation. Furthermore, AHPs grafted in the rostral migratory pathway migrated into the olfactory bulb, differentiating into tyrosine- hydroxylase-positive neurons, a non-hippocampus phenotype. These results reveal that AHP populations can respond to persistent neuronal differentiation cues in the adult central nervous system.}, Author = {Suhonen, J. O. and Peterson, D. A. and Ray, J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:41 -0400}, Journal = {Nature}, Keywords = {Human;Cell Differentiation;Stem Cells/cytology/transplantation;Cells, Cultured;Rats;Neurons/*cytology;Cerebellum/cytology;Female;Animal;Cell Movement;Rats, Inbred F344;Olfactory Pathways/*cytology;B;Olfactory Bulb/cytology;Support, Non-U.S. Gov't;Adult;Support, U.S. Gov't, P.H.S.;Hippocampus/*cytology}, Number = {6601}, Organization = {Laboratory of Genetics, The Salk Institute, La Jolla, California 92037- 1099, USA.}, Pages = {624-7.}, Title = {Differentiation of adult hippocampus-derived progenitors into olfactory neurons in vivo}, Uuid = {AD8B0CAA-A3E5-11DA-AB00-000D9346EC2A}, Volume = {383}, Year = {1996}, url = {papers/Suhonen_Nature1996.pdf}} @article{Sultan:2002, Abstract = {The mammalian brain is composed of several distinct parts which show different growth in evolution. Clark, Mitra and Wang found that the two main cortices of the brain - the cerebral (neo-) cortex and the cerebellum - show very different growth, and that whereas the ratio of neocortex volume to total brain volume increases with evolution, the cerebellum occupies a constant proportion in different species. Here I compare the surface areas of the two cortices in different species and find that these show a simple proportionality. Contrary to the conclusion drawn by Clark et al., this linear dependence of size implies that the two major cortices increase their computational capacity in parallel, suggesting a functional dependence of the one upon the other. 0028-0836 Comment Journal Article}, Author = {Sultan, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Nature}, Keywords = {Cerebellum/anatomy &histology;Human;Mammals;Models, Neurological;Brain/*anatomy &histology;Neocortex/anatomy &histology;Surface Properties;N;Primates/anatomy &histology;Animals;Cerebral Cortex/anatomy &histology;*Evolution;19 Neocortical evolution;Body Weights and Measures}, Number = {6868}, Organization = {Department of Cognitive Neurology, University of Tubingen, Germany. fahad.sultan\@uni-tuebingen.de}, Pages = {133-4}, Pubmed = {11805821}, Title = {Analysis of mammalian brain architecture}, Uuid = {DFE00301-6821-427F-BFA0-AD6D0F98651E}, Volume = {415}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11805821}} @article{Sun:1997, Abstract = {The features of a glial cell population in the developing brain of mice prenatally exposed to 60Co gamma-irradiation at the most radiosensitive stage were studied with immunohistochemistry for anti-midkine (MK), anti-vimentin (Vim), and anti-GFAP antibodies. Anti-MK- and anti-Vim- positive radial glial fibers distributed in a similar radial fashion; these fibers were observed primarily in the embryonic period and disappeared after birth. Anti-MK- and anti-Vim-stained radial fibers ran perpendicular to the pial surface in controls, whereas such fibers were disorganized 6 hours (h) after irradiation. This finding provided new evidence that the migratory pathways of young neurons were interrupted beginning a few hours after irradiation. By E17 the ectopic cell masses formed so as to replace the parts of the ventricular zone where no anti-MK immunoreactive radial fibers were present, but where anti-GFAP-stained fibrillary astrocytes emerged in the ectopic cell masses from the early postnatal period. The results suggested a twofold source of the generated astrocytes: either directly from a separate precursor of the astrocytes, or due to the transformation of the classic radial glial cells. In the newborn, numerous protoplasmic transitional forms displaced by astrocytes in irradiated brains indicated that reactive gliosis was a powerful response of a brain exposed to irradiation.}, Author = {Sun, X. Z. and Inouye, M. and Fukui, Y. and Hisano, S. and Sawada, K. and Muramatsu, H. and Muramatsu, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neuropathol Exp Neurol}, Keywords = {G;Pregnancy;Glial Fibrillary Acidic Protein/metabolism;Female;Animal;Neuroglia/*metabolism/pathology;*Prenatal Exposure Delayed Effects;11 Glia;Mice, Inbred ICR;Support, Non-U.S. Gov't;Carrier Proteins/metabolism;Vimentin/metabolism;Brain/embryology/*metabolism/pathology;Nerve Fibers/metabolism/pathology;Fetus/*radiation effects;Mice;Immunohistochemistry;*Gamma Rays}, Number = {12}, Organization = {Department of Anatomy, School of Medicine, Tokushima University, Japan.}, Pages = {1339-48.}, Title = {An immunohistochemical study of radial glial cells in the mouse brain prenatally exposed to gamma-irradiation}, Uuid = {81091F1C-8E21-458D-AB13-CA7994840C5C}, Volume = {56}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9413282}} @article{Sun:2005, Abstract = {It has been debated whether asymmetric distribution of cell surface receptors during mitosis could generate asymmetric cell divisions by yielding daughters with different environmental responsiveness and, thus, different fates. We have found that in mouse embryonic forebrain ventricular and subventricular zones, the EGFR can distribute asymmetrically during mitosis in vivo and in vitro. This occurs during divisions yielding two Nestin+ progenitor cells, via an actin-dependent mechanism. The resulting sibling progenitor cells respond differently to EGFR ligand in terms of migration and proliferation. Moreover, they express different phenotypic markers: the EGFRhigh daughter usually has radial glial/astrocytic markers, while its EGFRlow sister lacks them, indicating fate divergence. Lineage trees of cultured cortical glioblasts reveal repeated EGFR asymmetric distribution, and asymmetric divisions underlie formation of oligodendrocytes and astrocytes in clones. These data suggest that asymmetric EGFR distribution contributes to forebrain development by creating progenitors with different proliferative, migratory, and differentiation responses to ligand.}, Author = {Sun, Yu and Goderie, Susan K. and Temple, Sally}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Cell Differentiation;Animals;Receptor, Epidermal Growth Factor;Astrocytes;Cells, Cultured;Phenotype;Mitosis;Oligodendroglia;Cell Movement;Cell Proliferation;Prosencephalon;Research Support, U.S. Gov't, P.H.S.;Cell Lineage;Cerebral Cortex;Intermediate Filament Proteins;Epidermal Growth Factor;Mice;Actins;Stem Cells;Nerve Tissue Proteins;Biological Markers;Receptor Aggregation}, Month = {3}, Nlm_Id = {8809320}, Number = {6}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA.}, Pages = {873-86}, Pii = {S0896-6273(05)00114-5}, Pubmed = {15797549}, Title = {Asymmetric distribution of EGFR receptor during mitosis generates diverse CNS progenitor cells}, Uuid = {15F32482-C69A-48AA-A4A3-A39DD8B9096A}, Volume = {45}, Year = {2005}, url = {papers/Sun_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.01.045}} @article{Sun:2006, Abstract = {Rett syndrome (RTT) is an X-linked postnatal neurodevelopmental disorder, which is primarily caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2). A number of MeCP2 target genes have been identified, including the neurotrophic factor BDNF; however, the functional relevance of these targets has not been established. In this issue of Neuron, Chang et al. provide the first in vivo evidence for a functional interaction between BDNF and MeCP2.}, Author = {Sun, Yi E. and Wu, Hao}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Models, Biological;Methyl-CpG-Binding Protein 2;21 Neurophysiology;Rett Syndrome;comment;Brain-Derived Neurotrophic Factor;Animals;Humans;24 Pubmed search results 2008;review}, Month = {2}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, University of California, Los Angeles, 635 Charles E. Young Drive South, Los Angeles, California 91301, USA.}, Pages = {321-3}, Pii = {S0896-6273(06)00043-2}, Pubmed = {16446133}, Title = {The ups and downs of BDNF in Rett syndrome}, Uuid = {F4AA2220-E345-4E6B-9107-30602C3E9B02}, Volume = {49}, Year = {2006}, url = {papers/Sun_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.01.014}} @article{Sun:2000, Abstract = {Quantitative reverse transcriptase - polymerase chain reaction was used to analyze the relative expressions of NR1, NR2A, NR2B, NR2C, NR2D, and NR3 subunits of the NMDA receptor in the piriform, entorhinal, visual, and motor cortices as well as in the olfactory bulb of adult rat. The analysis detected clear differences in the relative proportions of the NMDA receptor subunits between the five forebrain regions examined. These differences were particularly striking when the piriform and motor cortices were compared. In the piriform cortex, NR1 was the predominant transcript. The expression of NR2A was only slightly higher than half of that of NR1. NR2B was expressed even at lower levels ( approximately 30\%of NR1). NR2C and NR3 were expressed at levels which were approximately 15\%of those of NR1. NR2D had the lowest levels of expression ( approximately 3\%of NR1). In contrast, NR2B was the predominant transcript in the motor cortical region, where it was expressed at the levels close to 135\%of those of NR1 message. NR2A had the levels of expression of approximately 50\%of those of NR1. The NR2C expression was close to 25\%that of NR1, and the NR2D and NR3 transcripts were totally absent from this cortical area. These findings suggest a significant regional variability of the NMDA receptors in the adult rat forebrain. 0887-4476 Journal Article}, Author = {Sun, L. and Shipley, M. T. and Lidow, M. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Synapse}, Keywords = {Receptors, N-Methyl-D-Aspartate/*metabolism;I;Rats;Cerebral Cortex/*metabolism;Olfactory Bulb/*metabolism;Support, U.S. Gov't, Non-P.H.S.;RNA, Messenger/*metabolism;Support, U.S. Gov't, P.H.S.;Animals;Male;13 Olfactory bulb anatomy}, Number = {3}, Organization = {Department of Oral and Craniofacial Biological Sciences, University of Maryland, Baltimore, Maryland 21201, USA.}, Pages = {212-21}, Pubmed = {10657028}, Title = {Expression of NR1, NR2A-D, and NR3 subunits of the NMDA receptor in the cerebral cortex and olfactory bulb of adult rat}, Uuid = {66F2BECE-FC1B-455B-B40F-F966927FA07B}, Volume = {35}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10657028}} @article{Sundholm-Peters:2004, Abstract = {During development radial glia (RG) are neurogenic, provide a substrate for migration, and transform into astrocytes. Cells in the RG lineage are functionally and biochemically heterogeneous in subregions of the brain. In the subventricular zone (SVZ) of the adult, astrocyte-like cells exhibit stem cell properties. During examination of the response of SVZ astrocytes to brain injury in adult mice, we serendipitously found a population of cells in the walls of the ventral lateral ventricle (LV) that were morphologically similar to RG. The cells expressed vimentin, glial fibrillary acidic protein (GFAP), intermediate filament proteins expressed by neural progenitor cells, RG and astrocytes. These RG-like cells had long processes extending ventrally into the nucleus accumbens, ventromedial striatum, ventrolateral septum, and the bed nucleus of the stria terminalis. The RG-like cell processes were associated with a high density of doublecortin-positive cells. Lesioning the cerebral cortex did not change the expression of vimentin and GFAP in RG-like cells, nor did it alter their morphology. To study the ontogeny of these cells, we examined the expression of molecules associated with RG during development: vimentin, astrocyte-specific glutamate transporter (GLAST), and brain lipid-binding protein (BLBP). As expected, vimentin was expressed in RG in the ventral LV embryonically (E16, E19) and during the first postnatal week (P0, P7). At P14, P21, P28 as well as in the adult (8-12 weeks), the ventral portion of the LV retained vimentin immunopositive RG-like cells, whereas RG largely disappeared in the dorsal two-thirds of the LV. GLAST and BLBP were expressed in RG of the ventral LV embryonically and through P7. In contrast to vimentin, at later stages BLBP and GLAST were found in RG-like cell somata but not in their processes. Our results show that cells expressing vimentin and GFAP (in the radial glia-astrocyte lineage) are heterogeneous dorsoventrally in the walls of the LV. The results suggest that not all RG in the ventral LV complete the transformation into astrocytes and that the ventral SVZ may be functionally dissimilar from the rest of the SVZ. 0300-4864 Journal Article}, Author = {Sundholm-Peters, N. L. and Yang, H. K. and Goings, G. E. and Walker, A. S. and Szele, F. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:59 -0400}, Journal = {J Neurocytol}, Keywords = {B, G pdf;02 Adult neurogenesis migration}, Number = {1}, Organization = {2430 N. Halsted, No. 209, CMIER Neurobiology Program, Children's Memorial Hospital, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60614-3394, USA.}, Pages = {153-64}, Title = {Radial glia-like cells at the base of the lateral ventricles in adult mice}, Uuid = {6D0C4FC8-156F-425A-8C2C-0EC4FCDD7A5A}, Volume = {33}, Year = {2004}, url = {papers/Sundholm-Peters_JNeurocytol2004.pdf}} @article{Sunnemark:2005, Abstract = {BACKGROUND: Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). It is associated with local activation of microglia and astroglia, infiltration of activated macrophages and T cells, active degradation of myelin and damage to axons and neurons. The proposed role for CX3CL1 (fractalkine) in the control of microglia activation and leukocyte infiltration places this chemokine and its receptor CX3CR1 in a potentially strategic position to control key aspects in the pathological events that are associated with development of brain lesions in MS. In this study, we examine this hypothesis by analyzing the distribution, kinetics, regulation and cellular origin of CX3CL1 and CX3CR1 mRNA expression in the CNS of rats with an experimentally induced MS-like disease, myelin oligodendrocyte glycoprotein (MOG)-induced autoimmune encephalomyelitis (EAE). METHODS: The expression of CX3CL1 and its receptor CX3CR1 was studied with in situ hybridization histochemical detection of their mRNA with radio labeled cRNA probes in combination with immunohistochemical staining of phenotypic cell markers. Both healthy rat brains and brains from rats with MOG-induced EAE were analyzed. In defined lesional stages of MOG-induced EAE, the number of CX3CR1 mRNA-expressing cells and the intensity of the in situ hybridization signal were determined by image analysis. Data were statistically evaluated by ANOVA, followed by Tukey's multiple comparison test. RESULTS: Expression of CX3CL1 mRNA was present within neuronal-like cells located throughout the neuraxis of the healthy rat. Expression of CX3CL1 remained unaltered in the CNS of rats with MOG-induced EAE, with the exception of an induced expression in astrocytes within inflammatory lesions. Notably, the brain vasculature of healthy and encephalitic animals did not exhibit signs of CX3CL1 mRNA expression. The receptor, CX3CR1, was expressed by microglial cells in all regions of the healthy brain. Induction of MOG-induced EAE was associated with a distinct accumulation of CX3CR1 mRNA expressing cells within the inflammatory brain lesions, the great majority of which stained positive for markers of the microglia-macrophage lineage. Analysis in time-staged brain lesions revealed elevated levels of CX3CR1 mRNA in microglia in the periplaque zone, as well as a dramatically enhanced accumulation of CX3CR1 expressing cells within the early-active, late-active and inactive, demyelinated lesions. CONCLUSIONS: Our data demonstrate constitutive and regulated expression of the chemokine CX3CL1 and its receptor CX3CR1 by neurons/astrocytes and microglia, respectively, within the normal and inflamed rat brain. Our findings propose a mechanism by which neurons and reactive astrocytes may control migration and function of the surrounding microglia. In addition, the accumulation of CX3CR1 expressing cells other than microglia within the inflammatory brain lesions indicate a possible role for CX3CL1 in controlling invasion of peripheral leucocytes to the brain.}, Author = {Sunnemark, and Eltayeb, and Nilsson, and Wallstrom, and Lassmann, and Olsson, and Berg, and Ericsson-Dahlstrand,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1742-2094}, Journal = {J Neuroinflammation}, Keywords = {11 Glia}, Month = {7}, Nlm_Id = {101222974}, Number = {1}, Pages = {17}, Pii = {1742-2094-2-17}, Pubmed = {16053521}, Title = {CX3CL1 (fractalkine) and CX3CR1 expression in myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis: kinetics and cellular origin}, Uuid = {7A4486E9-E487-446C-B61B-86A2A5DE2C75}, Volume = {2}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1742-2094-2-17}} @article{Super:1998, Abstract = {During neural development, specific recognition molecules provide the cues necessary for the formation of initial projection maps, which are reshaped later in development. In some systems, guiding cues for axonal pathfinding and target selection are provided by specific cells that are present only at critical times. For instance, the floor plate guides commissural axons in the spinal cord, and the subplate is involved in the formation of thalamocortical connections. Here we study the development of entorhinal and commissural connections to the murine hippocampus, which in the adult terminate in nonoverlapping layers. We show that two groups of pioneer neurons, Cajal-Retzius cells and GABAergic neurons, form layer-specific scaffolds that overlap with distinct hippocampal afferents at embryonic and early postnatal stages. Furthermore, at postnatal day 0 (P0)-P5, before the dendrites of pyramidal neurons develop, these pioneer neurons are preferential synaptic targets for hippocampal afferents. Birthdating analysis using 5'-bromodeoxyuridine (BrdU) pulses showed that most such early-generated neurons disappear at late postnatal stages, most likely by cell death. Together with previous studies, these findings indicate that distinct pioneer neurons are involved in the guidance and targeting of different hippocampal afferents.}, Author = {Sup\`{e}r, H. and Mart{\'\i}nez, A. and Del R{\'\i}o, J. A. and Soriano, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Aging;Synapses;Research Support, Non-U.S. Gov't;Hippocampus;Neural Pathways;Time Factors;Animals, Newborn;Neurons, Afferent;Animals;Mice;24 Pubmed search results 2008;Mice, Inbred Strains;Neurons}, Medline = {98279072}, Month = {6}, Nlm_Id = {8102140}, Number = {12}, Organization = {Department of Animal and Plant Cell Biology, Faculty of Biology, University of Barcelona, Barcelona 08028, Spain.}, Pages = {4616-26}, Pubmed = {9614236}, Title = {Involvement of distinct pioneer neurons in the formation of layer-specific connections in the hippocampus}, Uuid = {1F27319A-561A-4919-B256-159F499A9621}, Volume = {18}, Year = {1998}} @article{Sur:2002, Abstract = {Two recent studies have tested whether synaptic learning rules, inferred earlier from work on cell cultures and brain slices, apply in intact brains. The evidence indicates that they do, and reveals interesting implications for brain development and perceptual learning.}, Author = {Sur, Mriganka and Schummers, James and Dragoi, Valentin}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Visual Cortex;Visual Perception;21 Neurophysiology;Neuronal Plasticity;in vitro ;Models, Neurological;Learning;Synaptic Transmission;Animals;Brain;Humans;review;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {9107782}, Number = {5}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 45 Carleton St, E25-235, Cambridge, Massachusetts 02139, USA. msur\@ai.mit.edu}, Pages = {R168-70}, Pii = {S0960982202007339}, Pubmed = {11882305}, Title = {Cortical plasticity: time for a change}, Uuid = {8A6E16B1-95DC-4E4A-9A32-4593E538777D}, Volume = {12}, Year = {2002}, url = {papers/Sur_CurrBiol2002.pdf}} @article{Sur:2001, Abstract = {The development of cortical layers, areas and networks is mediated by a combination of factors that are present in the cortex and are influenced by thalamic input. Electrical activity of thalamocortical afferents has a progressive role in shaping cortex. For early thalamic innervation and patterning, the presence of activity might be sufficient; for features that develop later, such as intracortical networks that mediate emergent responses of cortex, the spatiotemporal pattern of activity often has an instructive role. Experiments that route projections from the retina to the auditory pathway alter the pattern of activity in auditory thalamocortical afferents at a very early stage and reveal the progressive influence of activity on cortical development. Thus, cortical features such as layers and thalamocortical innervation are unaffected, whereas features that develop later, such as intracortical connections, are affected significantly. Surprisingly, the behavioural role of 'rewired' cortex is also influenced profoundly, indicating the importance of patterned activity for this key aspect of cortical function.}, Author = {Sur, M. and Leamey, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Visual Cortex;Retina;research support, non-u.s. gov't;21 Neurophysiology;research support, non-u.s. gov't ;Neuronal Plasticity;Ferrets;21 Activity-development;Neocortex;21 Circuit structure-function;Auditory Pathways;Animals;Thalamus;24 Pubmed search results 2008;review;Axons}, Month = {4}, Nlm_Id = {100962781}, Number = {4}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 45 Carleton Street, Cambridge, Massachusetts 02139, USA. msur\@ai.mit.edu}, Pages = {251-62}, Pii = {35067562}, Pubmed = {11283748}, Title = {Development and plasticity of cortical areas and networks}, Uuid = {39AE349B-633F-4528-A013-B24AAC430E79}, Volume = {2}, Year = {2001}, url = {papers/Sur_NatRevNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35067562}} @article{Sur:2005, Abstract = {The cerebral cortex of the human brain is a sheet of about 10 billion neurons divided into discrete subdivisions or areas that process particular aspects of sensation, movement, and cognition. Recent evidence has begun to transform our understanding of how cortical areas form, make specific connections with other brain regions, develop unique processing networks, and adapt to changes in inputs.}, Author = {Sur, Mriganka and Rubenstein, John L. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Animals;Humans;Gene Expression Regulation, Developmental;Neuronal Plasticity;Neural Pathways;review;Axons;research support, non-u.s. gov't;Nerve Net;Thalamus;Morphogenesis;research support, u.s. gov't, p.h.s.;Cerebral Cortex;21 Neurophysiology;21 Circuit structure-function;21 Activity-development;research support, n.i.h., extramural;Body Patterning;24 Pubmed search results 2008;Dominance, Ocular;Models, Neurological;Brain Mapping}, Month = {11}, Nlm_Id = {0404511}, Number = {5749}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, 77 Massachusetts Ave., 46-6237, Cambridge, MA 02139, USA. msur\@mit.edu}, Pages = {805-10}, Pii = {310/5749/805}, Pubmed = {16272112}, Title = {Patterning and plasticity of the cerebral cortex}, Uuid = {001747AC-7D44-4711-9966-3042053EDA71}, Volume = {310}, Year = {2005}, url = {papers/Sur_Science2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1112070}} @article{Surani:2001, Abstract = {Most cells contain the same set of genes and yet they are extremely diverse in appearance and functions. It is the selective expression and repression of genes that determines the specific properties of individual cells. Nevertheless, even when fully differentiated, any cell can potentially be reprogrammed back to totipotency, which in turn results in re-differentiation of the full repertoire of adult cells from a single original cell of any kind. Mechanisms that regulate this exceptional genomic plasticity and the state of totipotency are being unravelled, and will enhance our ability to manipulate stem cells for therapeutic purposes. 0028-0836 Journal Article Review Review, Tutorial}, Author = {Surani, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Nature}, Keywords = {Stem Cells/*physiology;*Genome;F abstr;10 Development;Genomic Imprinting;Human;Oocytes;Zygote;Support, Non-U.S. Gov't;Animals;Cell Differentiation/*genetics;Cell Nucleus;Germ Cells}, Number = {6859}, Organization = {Wellcome CRC Institute of Cancer and Developmental Biology and Physiology Laboratory, University of Cambridge, UK. as10021\@mole.bio.cam.ac.uk}, Pages = {122-8}, Pubmed = {11689958}, Title = {Reprogramming of genome function through epigenetic inheritance}, Uuid = {3A677250-E697-4F1C-B670-CEFB61206F58}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689958}} @article{Suter:2007, Abstract = {The projection neurons of the neocortex are produced in the pseudostratified ventricular epithelium (PVE) lining the embryonic lateral ventricles. Over a 7 d period in mouse, these neurons arise in an overlapping layer VI-to-II sequence and in an anterolateral to posteromedial gradient [the transverse neurogenetic gradient (TNG)]. At any time in the 7 d neurogenetic interval, a given PVE cell must know what class of precursor cell or neuron to form next. How this information is encoded in the PVE is not known. With comparative experiments in wild-type and double-transgenic mice, overexpressing the cell cycle inhibitor p27(Kip1), we show that a gradient of expression of Lhx2 (inferred from its mRNA levels), a LIM homeodomain transcription factor, together with a gradient in duration of the G1 phase of the cell cycle (T(G1)), are sufficient to specify a positional mapping system that informs the PVE cell what class of neuron to produce next. Lhx2 likely is representative of an entire class of transcription factors expressed along the TNG. This mapping system consisting of a combination of signals from two different sources is a novel perspective on the source of positional information for neuronal specification in the developing CNS.}, Author = {Suter, Bernhard and Nowakowski, Richard S. and Bhide, Pradeep G. and Caviness, Verne S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8102140}, Number = {40}, Organization = {Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.}, Pages = {10777-84}, Pii = {27/40/10777}, Pubmed = {17913911}, Title = {Navigating neocortical neurogenesis and neuronal specification: a positional information system encoded by neurogenetic gradients}, Uuid = {5B2DA9CC-AE09-498B-8143-B8432B055AFD}, Volume = {27}, Year = {2007}, url = {papers/Suter_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3091-07.2007}} @article{Sutor:1998, Abstract = {The role of gamma-aminobutyric acid B (GABA(B)) receptors in the generation and maintenance of bicuculline-induced epileptiform activity in rat neocortical slices was studied using electrophysiological methods. A block of GABA(B) receptors in the presence of functional GABA(A) receptor-mediated inhibition was not sufficient to induce epileptiform activity. In the presence of the GABA(A) receptor antagonist bicuculline (10 microM) and at suprathreshold stimulation, the GABA(B) receptor antagonist CGP 35348 (10-300 microM) significantly potentiated epileptiform activity. With stimulation at threshold intensity, low concentrations of CGP 35348 (10-30 microM) potentiated bicuculline-induced activity, whereas higher concentrations (100-300 microM) invariably led to a reversible suppression of stimulus-evoked epileptiform discharges. CGP 35348 also enhanced picrotoxin-induced epileptiform activity, but at higher concentrations it was considerably less effective in suppressing such epileptiform discharges. The GABA uptake inhibitor nipecotic acid partially mimicked the actions of CGP 35348: with stimulation at threshold intensity, it reversibly suppressed bicuculline-induced epileptiform field potentials, but it did not influence epileptiform activity induced by picrotoxin. We conclude that a postsynaptic blockade of GABA(B) receptors induces an amplification of epileptiform activity in neocortical slices disinhibited by GABA(A) receptor antagonists. An additional blockade of presynaptic GABA(B) receptors, especially under conditions of weak stimulation of the neurons, reduces the inhibitory auto-feedback control of GABA release, leading to a displacement of competitive antagonists from the postsynaptic GABA(A) receptor and hence, to a suppression of epileptiform activity induced by competitive GABA(A) receptor antagonists.}, Author = {Sutor, B. and Luhmann, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Animals;In Vitro;Rats;Synaptic Transmission;Neocortex;21 Epilepsy;Epilepsy;Rats, Wistar;Receptors, GABA-B;Bicuculline;21 Neurophysiology;Membrane Potentials;Organophosphorus Compounds;GABA Antagonists;Convulsants;24 Pubmed search results 2008;Microelectrodes;Research Support, Non-U.S. Gov't}, Medline = {99046841}, Month = {11}, Nlm_Id = {8918110}, Number = {11}, Organization = {Institute of Physiology, University of Munich, Germany. bernd.sutor\@lrz.uni-muenchen.de}, Pages = {3417-27}, Pubmed = {9824455}, Title = {Involvement of GABA(B) receptors in convulsant-induced epileptiform activity in rat neocortex in vitro}, Uuid = {0757FDFF-570C-46E2-A926-3C29A578C757}, Volume = {10}, Year = {1998}} @article{Sutton:2007, Abstract = {Activity-dependent regulation of dendritic protein synthesis is critical for enduring changes in synaptic function, but how the unique features of distinct activity patterns are decoded by the dendritic translation machinery remains poorly understood. Here, we identify eukaryotic elongation factor-2 (eEF2), which catalyzes ribosomal translocation during protein synthesis, as a biochemical sensor in dendrites that is specifically and locally tuned to the quality of neurotransmission. We show that intrinsic action potential (AP)-mediated network activity in cultured hippocampal neurons maintains eEF2 in a relatively dephosphorylated (active) state, whereas spontaneous neurotransmitter release (i.e., miniature neurotransmission) strongly promotes the phosphorylation (and inactivation) of eEF2. The regulation of eEF2 phosphorylation is responsive to bidirectional changes in miniature neurotransmission and is controlled locally in dendrites. Finally, direct spatially controlled inhibition of eEF2 phosphorylation induces local translational activation, suggesting that eEF2 is a biochemical sensor that couples miniature synaptic events to local translational suppression in neuronal dendrites.}, Author = {Sutton, Michael A. and Taylor, Anne M. and Ito, Hiroshi T. and Pham, Anh and Schuman, Erin M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Excitatory Amino Acid Antagonists;Animals;Cells, Cultured;Rats;Transfection;Synaptic Transmission;Diagnostic Imaging;Patch-Clamp Techniques;Eukaryotic Initiation Factor-2;Hippocampus;Tetrodotoxin;research support, non-u.s. gov't;Green Fluorescent Proteins;Dendrites;Analysis of Variance;Animals, Newborn;Action Potentials;21 Neurophysiology;Neurons;research support, n.i.h., extramural;Protein Biosynthesis;24 Pubmed search results 2008;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {8809320}, Number = {4}, Organization = {Division of Biology 114-96, California Institute of Technology, Pasadena, CA 91125, USA.}, Pages = {648-61}, Pii = {S0896-6273(07)00575-2}, Pubmed = {17698016}, Title = {Postsynaptic decoding of neural activity: eEF2 as a biochemical sensor coupling miniature synaptic transmission to local protein synthesis}, Uuid = {A6A4F575-59BB-4F16-B992-762EDA3428FE}, Volume = {55}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.07.030}} @article{Suzuki:2002, Abstract = {Neuronal progenitor cells (NPC) are particularly suited as the target population for genetic and cellular therapy of neurological disorders such as Parkinson's disease or stroke. However, genetic modification of these cells using retroviral vectors remains a great challenge because of the low transduction rate and the need for fetal calf serum (FCS) during the transduction process that induces the cell differentiation to mature neurons. To overcome these problems, we developed a new retrovirus production system in which the simplified retroviral vector GCDNsap engineered to be resistant to denovo methylation was packaged in the vesicular stomatitis virus G protein (VSV-G), concentrated by centrifugation, and resuspended in serum-free medium (StemPro-34 SFM). In transduction experiments using enhanced green fluorescent protein (EGFP) as a marker, the concentrated FCS-free virus supernatant infected NPC at a high rate, while maintaining the ability of these cells to self-renew and differentiate in vitro. When such cells were grafted into mouse brains, EGFP-expressing NPC were detected in the region around the injection site at 8 weeks post transplantation. These findings suggest that the gene transfer system described here may provide a useful tool to genetically modify NPC for treatments of neurological disorders.}, Author = {Suzuki, A. and Obi, K. and Urabe, T. and Hayakawa, H. and Yamada, M. and Kaneko, S. and Onodera, M. and Mizuno, Y. and Mochizuki, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Transduction, Genetic;Animals;Corpus Striatum;Cells, Cultured;Stem Cell Transplantation;Feasibility Studies;Nervous System Diseases;Mice, Inbred C57BL;Retroviridae;11 Glia;Male;Genetic Vectors;Viral Envelope Proteins;Membrane Glycoproteins;Gene Therapy;Mice;Genes, Reporter;Graft Survival;Clone Cells;Luminescent Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Medline = {22246909}, Month = {8}, Nlm_Id = {2985190R}, Number = {4}, Organization = {Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.}, Pages = {953-60}, Pii = {1048}, Pubmed = {12358801}, Title = {Feasibility of ex vivo gene therapy for neurological disorders using the new retroviral vector GCDNsap packaged in the vesicular stomatitis virus G protein}, Uuid = {5DD24BD8-12E3-4EA0-9756-C5FF2E0E63E3}, Volume = {82}, Year = {2002}} @article{Suzuki:2003, Abstract = {Neural progenitors in the subventricular zone (SVZ) of the postnatal rat forebrain give rise to either olfactory interneurons or glia. To investigate the overall patterns of progenitor movement, we labeled neonatal rat SVZ cells by stereotactic injection of a GFP-encoding retrovirus into the SVZ at various coronal levels. We then studied the movements of labeled cells by time-lapse videomicroscopy in living brain slices cut in different orientations. We observed two migration patterns: (1) progenitors migrated radially into the overlying white matter and cortex, but only at the level of viral injection; these were previously shown to give rise to astrocytes and oligodendrocytes, (2) progenitors migrated in a bidirectional, rostrocaudal pattern along the entire extent of the SVZ; many of these cells eventually migrated into the olfactory bulb and developed into interneurons, but they did not turn to migrate radially out of the SVZ until they reached the olfactory bulb. Video imaging showed apparent boundaries to migration between the SVZ and adjacent structures. These observations indicate that there are at least two distinct migratory pathways within the SVZ used differentially by immature neurons and glia. 1529-2401 Journal Article}, Author = {Suzuki, S. O. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {J Neurosci}, Keywords = {B both;Microscopy, Video;Neuroglia/cytology/physiology/virology;Stem Cells/cytology/physiology/virology;Animals;Rats;Cell Movement/*physiology;Vimentin/analysis;Neurons/cytology/physiology/virology;02 Adult neurogenesis migration;Kinetics;Rats, Sprague-Dawley;Brain/cytology/embryology/virology;Time Factors;Injections, Intraventricular;Prosencephalon/*cytology/physiology/virology;Cell Line;Animals, Newborn;Oligodendroglia/cytology/physiology;3T3 Cells;Olfactory Bulb/cytology/physiology/virology;Frontal Lobe/cytology/physiology/virology;Support, U.S. Gov't, P.H.S.;Mice;Cell Differentiation/physiology;Luminescent Proteins/metabolism;Astrocytes/cytology/physiology/virology}, Number = {10}, Organization = {Department of Pathology and the Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA. sosuzuki\@np.med.kyushu-u.ac.jp}, Pages = {4240-50}, Title = {Multiple cell populations in the early postnatal subventricular zone take distinct migratory pathways: a dynamic study of glial and neuronal progenitor migration}, Uuid = {E8D656A3-B86A-11DA-93EA-000D9346EC2A}, Volume = {23}, Year = {2003}, url = {papers/Suzuki_JNeurosci2003.pdf}} @article{Svendsen:2001, Abstract = {It is now possible to grow stem cells from a wide variety of tissues. Some of these cells have been shown to differentiate into presumptive neurons in vitro, or after transplantation into the developing or adult brain. When stem cells derived directly from the brain are induced to differentiate, there is a high probability that some of the resulting cells will be neurons. However, when stem cells from one tissue (for example, bone marrow or skin) take on the phenotype of another (for example, brain), rigorous criteria are required to define neurons. The aim of this review is to discuss the various techniques that are used to identify a cell as a neuron.}, Author = {Svendsen, C. N. and Bhattacharyya, A. and Tai, Y. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {02 Adult neurogenesis migration;B}, Number = {11}, Organization = {Clive N. Svendsen, Anita Bhattacharyya and Yu-Tzu Tai are members of the Stem Cell Research Program, Waisman Center and Departments of Anatomy and Neurology, University of Wisconsin, Madison, Wisconsin 53705-2280, USA.}, Pages = {831-4.}, Title = {Neurons from stem cells: preventing an identity crisis}, Uuid = {FC0CA5A8-4BD6-4280-BD2C-0E4AB71F250C}, Volume = {2}, Year = {2001}, url = {papers/Svendsen_NatRevNeurosci2001.pdf}} @article{Svoboda:2006, Abstract = {The brain is complex and dynamic. The spatial scales of interest to the neurobiologist range from individual synapses (approximately 1 microm) to neural circuits (centimeters); the timescales range from the flickering of channels (less than a millisecond) to long-term memory (years). Remarkably, fluorescence microscopy has the potential to revolutionize research on all of these spatial and temporal scales. Two-photon excitation (2PE) laser scanning microscopy allows high-resolution and high-sensitivity fluorescence microscopy in intact neural tissue, which is hostile to traditional forms of microscopy. Over the last 10 years, applications of 2PE, including microscopy and photostimulation, have contributed to our understanding of a broad array of neurobiological phenomena, including the dynamics of single channels in individual synapses and the functional organization of cortical maps. Here we review the principles of 2PE microscopy, highlight recent applications, discuss its limitations, and point to areas for future research and development.}, Author = {Svoboda, Karel and Yasuda, Ryohei}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Confocal;Research Support, Non-U.S. Gov't;Photobleaching;21 Neurophysiology;Neurosciences;Research Support, N.I.H., Extramural;Microscopy;Fluorescence;Multiphoton;Humans;Animals;review;optical physiology;optical imaging;Technique;Optics}, Month = {6}, Nlm_Id = {8809320}, Number = {6}, Organization = {HHMI, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA. svoboda\@cshl.edu}, Pages = {823-39}, Pii = {S0896-6273(06)00411-9}, Pubmed = {16772166}, Title = {Principles of two-photon excitation microscopy and its applications to neuroscience}, Uuid = {29D4A676-2017-42C6-B478-5E235B3BE2CC}, Volume = {50}, Year = {2006}, url = {papers/Svoboda_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.05.019}} @article{Swadlow:2001, Abstract = {Considerable effort has gone into understanding the mechanisms underlying high-frequency 'bursting' of thalamocortical impulses, their sensory information content and their involvement in perception. However, little is known about the influence of such impulses on their cortical targets. Here we follow bursting thalamic impulses to their terminus at the thalamocortical synapse of the awake rabbit, and examine their influence on a class of somatosensory cortical neurons. We show that thalamic bursts potently activate cortical circuits. Initial impulses of each burst have a greatly enhanced ability to elicit cortical action potentials, and later impulses in the burst further raise the probability of eliciting spikes. In some cases, multiple cortical spikes result from a single burst. Moreover, we show that the interval preceding each burst is crucial for generating the enhanced cortical response. The powerful activation of neocortex by thalamocortical bursts is fully consistent with an involvement of these impulses in perceptual/attentional processes.}, Author = {Swadlow, H. A. and Gusev, A. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Synapses;24 Pubmed search results 2008;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;research support, u.s. gov't, non-p.h.s. ;Electrophysiology;Rabbits;Animals;Somatosensory Cortex;Thalamus;Microelectrodes;Neurons}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {Department of Psychology, The University of Connecticut, 406 Babbidge Road, Storrs, Connecticut 06269, USA. swadlow\@psych.psy.uconn.edu}, Pages = {402-8}, Pii = {86054}, Pubmed = {11276231}, Title = {The impact of 'bursting' thalamic impulses at a neocortical synapse}, Uuid = {38A08784-398E-44FA-97BB-AF6CC83910AB}, Volume = {4}, Year = {2001}, url = {papers/Swadlow_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/86054}} @article{Swann:2000, Abstract = {The nervous system has an enhanced capacity to generate seizures during a restricted phase of postnatal development. Studies in animals and particularly in in vitro brain slices from hippocampus and neocortex have been instrumental in furthering an understanding of the underlying processes. Developmental alterations in glutaminergic excitatory synaptic transmission appear to play a key role in the enhanced seizure susceptible of rodents during the second and third week of life. Prior to this period, the number of excitatory synapses is relatively low. The scarcity of connections and the inability of the existing synapses to release glutamate when activated at high frequencies likely contribute importantly to the resistance of neonates to seizures. However, at the beginning of week 2, a dramatic outgrowth of excitatory synapses occurs, and these synapses are able to faithfully follow activation at high frequencies. These changes, coupled with the prolonged nature of synaptic potentials in early life, likely contribute to the ease of seizure generation. After this time, seizure susceptibility declines, patterns of local synaptic connectivity remodel, and some synapses are pruned. Concurrently, the duration of excitatory postsynaptic potentials shortens due at least in part to a switch in the subunit composition of postsynaptic receptors. Other studies have examined the mechanisms underlying chronic epilepsy initiated in early life. Models of both cortical dysplasia and recurrent early-life seizures suggest that alterations in the normal development of excitatory synaptic transmission can contribute importantly to chronic epileptic conditions. In the recurrent early-life seizure model, abnormal use-dependent selection of subpopulations of excitatory synapses may play a role. In experimental cortical dysplasia, alterations in the molecular composition of postsynaptic receptor are observed that favor subunit combinations characteristic of infancy.}, Author = {Swann, J. W. and Hablitz, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1080-4013}, Journal = {Ment Retard Dev Disabil Res Rev}, Keywords = {Causality;Receptors, Glutamate;gamma-Aminobutyric Acid;Animals;Synapses;Humans;Neuronal Plasticity;Neural Pathways;review;Synaptic Transmission;Brain;Epilepsy;21 Epilepsy;Hippocampus;Pyramidal Cells;Disease Models, Animal;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;21 Neurophysiology;Neurons;Age Factors;Excitatory Amino Acids;24 Pubmed search results 2008;Neural Inhibition}, Medline = {20561134}, Nlm_Id = {9517974}, Number = {4}, Organization = {The Cain Foundation Laboratories, Department of Pediatrics and Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA. jswann\@bcm.tmc.edu}, Pages = {258-67}, Pii = {10.1002/1098-2779(2000)6:4<258::AID-MRDD5>3.0.CO;2-H}, Pubmed = {11107191}, Title = {Cellular abnormalities and synaptic plasticity in seizure disorders of the immature nervous system}, Uuid = {438BB358-10E6-4662-9E5A-248637EC3C81}, Volume = {6}, Year = {2000}, url = {papers/Swann_MentRetardDevDisabilResRev2000.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/1098-2779(2000)6:4%3C258::AID-MRDD5%3E3.0.CO;2-H}} @article{Sweeney:2008, Abstract = {The sticky/citron kinase protein is a conserved regulator of cell-cycle progression from invertebrates to humans. While this kinase is essential for completion of cytokinesis, sticky/citron kinase phenotypes disrupting neurogenesis and cell differentiation suggest additional non-cell-cycle functions. However, it is not known whether these phenotypes are an indirect consequence of sticky mutant cell-cycle defects or whether they define a novel function for this kinase. We have isolated a temperature-sensitive allele of the Drosophila sticky gene and we show that sticky/citron kinase is required for histone H3-K9 methylation, HP1 localization, and heterochromatin-mediated gene silencing. sticky genetically interacts with Argonaute 1 and sticky mutants exhibit context-dependent Su(var) and E(var) activity. These observations indicate that sticky/citron kinase functions to regulate both actin-myosin-mediated cytokinesis and epigenetic gene silencing, possibly linking cell-cycle progression to heterochromatin assembly and inheritance of gene expression states.}, Author = {Sweeney, Sarah J. and Campbell, Paula and Bosco, Giovanni}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0016-6731}, Journal = {Genetics}, Keywords = {Chromosomal Proteins, Non-Histone;Animals;Cell Cycle;Female;Mutation;Protein-Serine-Threonine Kinases;Models, Genetic;Methylation;Heterochromatin;research support, non-u.s. gov't;Eye;Temperature;Alleles;Drosophila melanogaster;Histones;Gene Silencing;Intracellular Signaling Peptides and Proteins;research support, n.i.h., extramural;Ploidies;24 Pubmed search results 2008;Amino Acid Sequence;Molecular Sequence Data;Ovarian Follicle;Drosophila Proteins;Genes, Insect}, Month = {3}, Nlm_Id = {0374636}, Number = {3}, Organization = {Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.}, Pages = {1311-25}, Pii = {genetics.107.082511}, Pmc = {PMC2278101}, Pubmed = {18245345}, Title = {Drosophila sticky/citron kinase is a regulator of cell-cycle progression, genetically interacts with Argonaute 1 and modulates epigenetic gene silencing}, Uuid = {9681BE33-E73A-4AEB-81CF-149933CA044F}, Volume = {178}, Year = {2008}, url = {papers/Sweeney_Genetics2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1534/genetics.107.082511}} @article{Sychowa:1968, Author = {Sychowa, B. and Stepie\'{n}, L. and Stepie\'{n}, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0365-0820}, Journal = {Acta Biol Exp (Warsz)}, Keywords = {Nerve Degeneration;Neural Pathways;Dogs;Thalamus;Animals;24 Pubmed search results 2008;Frontal Lobe}, Medline = {69255827}, Nlm_Id = {1246764}, Number = {4}, Pages = {383-99}, Pubmed = {5732769}, Title = {Degeneration in the thalamus following medial frontal lesions in the dog}, Uuid = {04E5FE10-B69E-4C3D-8B9E-CE30AF6FEAB2}, Volume = {28}, Year = {1968}} @article{Syken:2006, Abstract = {Experience can alter synaptic connectivity throughout life, but the degree of plasticity present at each age is regulated by mechanisms that remain largely unknown. Here we demonstrate that PirB, an MHC Class I (MHCI) receptor, is expressed in subsets of neurons throughout the brain. Neuronal PirB protein is associated with synapses and forms complexes with the phosphatases Shp-1 and Shp-2. Soluble PirB fusion protein binds to cortical neurons in an MHCI-dependent manner. In mutant mice lacking functional PirB, cortical ocular dominance (OD) plasticity is more robust at all ages. Thus, an MHCI receptor is expressed in CNS neurons and functions to limit the extent of experience-dependent plasticity in the visual cortex throughout life. PirB is also expressed in many other regions of the CNS, suggesting that it may function broadly to stabilize neural circuits.}, Author = {Syken, and Grandpre, and Kanold, and Shatz,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {21 Neurophysiology;21 Activity-development;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {0404511}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Pii = {1128232}, Pubmed = {16917027}, Title = {PirB Restricts Ocular-Dominance Plasticity in Visual Cortex}, Uuid = {2B1D52E9-0A32-4F5A-A6FA-C4060DF8A0C8}, Year = {2006}, url = {papers/Syken_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1128232}} @article{Szabadics:2006, Abstract = {Axons in the cerebral cortex receive synaptic input at the axon initial segment almost exclusively from gamma-aminobutyric acid-releasing (GABAergic) axo-axonic cells (AACs). The axon has the lowest threshold for action potential generation in neurons; thus, AACs are considered to be strategically placed inhibitory neurons controlling neuronal output. However, we found that AACs can depolarize pyramidal cells and can initiate stereotyped series of synaptic events in rat and human cortical networks because of a depolarized reversal potential for axonal relative to perisomatic GABAergic inputs. Excitation and signal propagation initiated by AACs is supported by the absence of the potassium chloride cotransporter 2 in the axon.}, Author = {Szabadics, J{\'a}nos and Varga, Csaba and Moln{\'a}r, G{\'a}bor and Ol{\'a}h, Szabolcs and Barz{\'o}, P{\'a}l and Tam{\'a}s, G{\'a}bor}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {gamma-Aminobutyric Acid;in vitro;Animals;Humans;Rats;Middle Aged;Symporters;Axons;Pyramidal Cells;Rats, Wistar;research support, non-u.s. gov't;Action Potentials;Cerebral Cortex;Neurons;21 Neurophysiology;research support, n.i.h., extramural;24 Pubmed search results 2008;Neural Inhibition;Excitatory Postsynaptic Potentials}, Month = {1}, Nlm_Id = {0404511}, Number = {5758}, Organization = {Department of Comparative Physiology, University of Szeged, K{\"o}z\`{e}p fasor 52, Szeged, H-6726, Hungary.}, Pages = {233-5}, Pii = {311/5758/233}, Pubmed = {16410524}, Title = {Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits}, Uuid = {7222999C-F63C-4061-B9B5-EC9ACE179601}, Volume = {311}, Year = {2006}, url = {papers/Szabadics_Science2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1121325}} @article{Szele:1996, Abstract = {The subventricular zone (SVZ) bordering the lateral ventricle is one of the few regions of adult brain that contains dividing cells. These cells can differentiate into neurons in vivo after migration into the olfactory bulb and in vitro in the presence of appropriate growth factors. Little is known, however, about the fate of these cells in vivo after brain injury in adults. We examined cell number and expression of differentiation markers in the SVZ of adult rats after cortical lesions. Aspiration lesions of the sensorimotor cortex in adult rats induced a transient doubling of the number of cells in the SVZ at the level of the striatum without consistent increases in bromodeoxyuridine-labeled cells. Immunoreactivity to the polysialylated neural cell adhesion molecule, expressed by the majority of cells of the SVZ during development, increased dramatically after lesion. In contrast, immunolabeling for molecules found in mature neurons and glia did not increase in the SVZ after lesion, and immunoreactivity for growth factors that induce differentiation of SVZ cells in vitro decreased or remained undetectable, suggesting that lack of appropriate growth factor expression may contribute to the lack of differentiation of the newly accumulated cells in vivo. The data reveal that cells of the SVZ are capable of plasticity in the adult rat after brain injury in vivo and that the newly accumulated cells retain characteristics seen during development.}, Author = {Szele, F. G. and Chesselet, M. F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Comp Neurol}, Keywords = {B-6;Growth Substances/biosynthesis;Rats;Neural Cell Adhesion Molecules/analysis/*biosynthesis;Cell Movement/*physiology;Animal;Neuroglia/chemistry;02 Adult neurogenesis migration;Cell Count;Male;Cerebral Ventricles/*chemistry/*cytology;Neostriatum/chemistry/cytology;Support, U.S. Gov't, P.H.S.;Rats, Sprague-Dawley/*physiology;Intermediate Filament Proteins/analysis;Immunohistochemistry;Biological Markers;Bromodeoxyuridine;Neurons/chemistry;Sialic Acids/analysis/*biosynthesis}, Number = {3}, Organization = {Department of Pharmacology, University of Pennsylvania, Philadelphia 19104, USA.}, Pages = {439-54.}, Title = {Cortical lesions induce an increase in cell number and PSA-NCAM expression in the subventricular zone of adult rats}, Uuid = {78CB2857-3612-41F5-BB01-D946A0D8ABA5}, Volume = {368}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8725350}} @article{Szirmai:1980, Author = {Szirmai, I. and Vollmer, R. and Lapins, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0300-5186}, Journal = {Monogr Neural Sci}, Keywords = {Epilepsy;24 Pubmed search results 2008;Electroencephalography;21 Epilepsy;21 Neurophysiology;Rabbits;Animals;Cerebral Cortex;Acetylcholine;Electrodes, Implanted}, Medline = {82103776}, Nlm_Id = {0357002}, Pages = {25-9}, Pubmed = {7322161}, Title = {Analysis of cortical spread of acetylcholine (ACh)--induced epileptiform discharges}, Uuid = {00966560-7F08-4482-BA93-F67CE8B775AD}, Volume = {5}, Year = {1980}} @article{Tabar:2005, Abstract = {Human embryonic stem (hES) cells provide a potentially unlimited cell source for regenerative medicine. Recently, differentiation strategies were developed to direct hES cells towards neural fates in vitro. However, the interaction of hES cell progeny with the adult brain environment remains unexplored. Here we report that hES cell-derived neural precursors differentiate into neurons, astrocytes and oligodendrocytes in the normal and lesioned brain of young adult rats and migrate extensively along white matter tracts. The differentiation and migration behavior of hES cell progeny was region specific. The hES cell-derived neural precursors integrated into the endogenous precursor pool in the subventricular zone, a site of persistent neurogenesis. Like adult neural stem cells, hES cell-derived precursors traveled along the rostral migratory stream to the olfactory bulb, where they contributed to neurogenesis. We found no evidence of cell fusion, suggesting that hES cell progeny are capable of responding appropriately to host cues in the subventricular zone.}, Author = {Tabar, and Panagiotakos, and Greenberg, and Chan, and Sadelain, and Gutin, and Studer,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {22 Stem cells}, Month = {4}, Nlm_Id = {9604648}, Number = {5}, Organization = {[1] Developmental Biology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York 10021, USA. [2] Neurosurgery, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, New York 10021, USA.}, Pages = {601-6}, Pii = {nbt1088}, Pubmed = {15852001}, Title = {Migration and differentiation of neural precursors derived from human embryonic stem cells in the rat brain}, Uuid = {330CEE8B-271F-400D-9623-8CB5613FC5C4}, Volume = {23}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt1088}} @article{Tabata:2003, Abstract = {Two distinct modes of radial neuronal migration, locomotion and somal translocation, have been reported in the developing cerebral cortex. Although these two modes of migration have been well documented, the cortical intermediate zone contains abundant multipolar cells, and they do not resemble the cells migrating by locomotion or somal translocation. Here, we report that these multipolar cells express neuronal markers and extend multiple thin processes in various directions independently of the radial glial fibers. Time-lapse analysis of living slices revealed that the multipolar cells do not have any fixed cell polarity, and that they very dynamically extend and retract multiple processes as their cell bodies slowly move. They do not usually move straight toward the pial surface during their radial migration, but instead frequently change migration direction and rate; sometimes they even remain in almost the same position, especially when they are in the subventricular zone. Occasionally, the multipolar cells jump tangentially during their radial migration. Because the migration modality of these cells clearly differs from locomotion or somal translocation, we refer to their novel type of migration as "multipolar migration."In view of the high proportion of cells exhibiting multipolar migration, this third mode of radial migration must be an important type of migration in the developing cortex. 1529-2401 Journal Article}, Author = {Tabata, H. and Nakajima, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurosci}, Keywords = {Gene Transfer Techniques;Genes, Reporter;10 Development;Luminescent Proteins/biosynthesis/genetics;Interneurons/cytology/metabolism;Antigens, Differentiation/biosynthesis;In Vitro;Lateral Ventricles/cytology;Mice, Inbred ICR;Neurons/*cytology/metabolism;Electroporation;Cell Movement/*physiology;Animals;Support, Non-U.S. Gov't;Mice;Cerebral Cortex/*cytology/*embryology;F pdf}, Number = {31}, Organization = {Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.}, Pages = {9996-10001}, Pubmed = {14602813}, Title = {Multipolar migration: the third mode of radial neuronal migration in the developing cerebral cortex}, Uuid = {EEBB8283-067E-49E2-B145-850E95463409}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14602813}} @article{Takagi:1999, Abstract = {We investigated the proliferation of neuronal progenitor cells by labeling dividing cells by systemic application of the thymidine analog 5-bromodeoxyuridine (BrdU) during transient forebrain ischemia in mice. At 3 (n=6), 7 (n=6), 10 (n=6), and 17 days (n=6) after reperfusion, BrdU-labeled cells were detected in the dentate gyrus and paraventricle lesion. After ischemia-reperfusion, BrdU-labeled cells in the dentate gyrus significantly increased in number but not in the paraventricle lesion. These observations may help to clarify the mechanism of functional recovery after stroke. 0006-8993 Journal Article}, Author = {Takagi, Y. and Nozaki, K. and Takahashi, J. and Yodoi, J. and Ishikawa, M. and Hashimoto, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Brain Res}, Keywords = {Mice;Male;Dentate Gyrus/*pathology;D abstr;In Situ Nick-End Labeling;Prosencephalon/*blood supply;Ischemic Attack, Transient/*pathology;Cell Division/physiology;Time Factors;Mice, Inbred C57BL;06 Adult neurogenesis injury induced;Animals;Bromodeoxyuridine;Support, Non-U.S. Gov't;Neurons/*pathology;Stem Cells/*pathology}, Number = {1-2}, Organization = {Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Sakyo, Kyoto, Japan.}, Pages = {283-7}, Pubmed = {10412007}, Title = {Proliferation of neuronal precursor cells in the dentate gyrus is accelerated after transient forebrain ischemia in mice}, Uuid = {1F5F517B-EC81-11DA-8605-000D9346EC2A}, Volume = {831}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10412007}} @article{Takahashi:1990, Abstract = {Cells of astroglial lineage in the murine cerebrum undergo a succession of transformations during prenatal and early postnatal development. The bipolar radial cell, the earliest astroglial form to appear, provides a radially aligned, parallel array of fibers that serves as a guide to neuronal migration. The multipolar astrocyte is the representative of this lineage that persists in the adult cerebrum. The processes of the multipolar astrocytes form a complex reticulum, which is considered critical to the development, function, and maintenance of neural circuits. A monopolar radial cell appears to be transitional between the two. The shift from the radial glial fiber system to a diffuse glial network is achieved largely in the E17-P2 interval in the mouse. This phenomenon has been studied qualitatively and quantitatively by staining cerebral tissue with monoclonal antibody RC2, a specific and sensitive ligand for cells of astroglial lineage in the mouse. Elongation and branching of glial processes contribute to the glial transformation. Elongation of radial fibers occurs under the guidance of other radial glial fibers (fasciculated elongation) or independently of other fibers (nonfasciculated elongation). Fasciculated elongation results in an increase in the density of radial glial fibers that span the cortical layers. Nonfasciculated elongation appears to be associated with process branching. This is the initial event in transformation of the bipolar radial cells to monopolar radial or multipolar cells. Only nonfasciculated elongation is characteristic of processes of the monopolar radial cells and multipolar astrocytes. Branching of the processes of all three cell forms appears to occur both by bifurcation at the elongating tip and by sprouting from the fiber shaft. Elongating fibers are tipped by growth cones that are relatively simple in shape as compared to those observed at the tips of elongating axons. Growth cones at the tips of nonfasciculated fibers are more complex in form than those at the tips of radial fibers elongating in contact with other radial fibers.}, Author = {Takahashi, T. and Misson, J. P. and Caviness, V. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Comp Neurol}, Keywords = {Astrocytes/chemistry/*ultrastructure;Animal;11 Glia;Cell Differentiation/physiology;Support, U.S. Gov't, P.H.S.;Immunoenzyme Techniques;Support, Non-U.S. Gov't;G;Mice;Fetal Development/physiology;Cerebral Cortex/embryology/growth &development/*ultrastructure}, Number = {1}, Organization = {Department of Neurology, Massachusetts General Hospital, Boston 02114.}, Pages = {15-28.}, Title = {Glial process elongation and branching in the developing murine neocortex: a qualitative and quantitative immunohistochemical analysis}, Uuid = {A6DF4110-A5F4-4192-9381-249C147316E3}, Volume = {302}, Year = {1990}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=2086612}} @article{Takahashi:1999, Abstract = {ABSTRACT: The adult rat hippocampus contains fibroblast growth factor 2- responsive stem cells that are self-renewing and have the ability to generate both neurons and glia in vitro, but little is known about the molecular events that regulate stem cell differentiation. Hippocampus- derived stem cell clones were used to examine the effects of retinoic acid (RA) on neuronal differentiation. Exposure to RA caused an immediate up-regulation of NeuroD, increased p21 expression, and concurrent exit from cell cycle. These changes were accompanied by a threefold increase in the number of cells differentiating into immature neurons. An accompanying effect of RA was to sustain or up-regulate trkA, trkB, trkC, and p75NGFR expression. Without RA treatment, cells were minimally responsive to neurotrophins (NTs), whereas the sequential application of RA followed by brain-derived neurotrophic factor or NT-3 led to a significant increase in neurons displaying mature y-a-minobutyric acid, acetylcholinesterase, tyrosine hydroxylase, or calbindin phenotypes. Although NTs promoted maturation, they had little effect on the total number of neurons generated, suggesting that RA and neurotrophins acted at distinct stages in neurogenesis. RA first promoted the acquisition of a neuronal fate, and NTs subsequently enhanced maturation by way of RA-dependent expression of the Trk receptors. In combination, these sequential effects were sufficient to stimulate stem cell-derived progenitors to differentiate into neurons displaying a variety of transmitter phenotypes.}, Author = {Takahashi, J. and Palmer, T. D. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurobiol}, Keywords = {Cell Differentiation/drug effects;Proto-Oncogene Proteins/drug effects/metabolism;Receptor, trkA;Stem Cells/*drug effects/physiology;Tretinoin/*pharmacology;Up-Regulation (Physiology);Gene Expression Regulation, Developmental;Receptor Protein-Tyrosine Kinases/drug effects/metabolism;Rats;Neurons/cytology/*drug effects;Nerve Growth Factors/pharmacology;Animal;C abstr;Hippocampus;Reverse Transcriptase Polymerase Chain Reaction;Support, Non-U.S. Gov't;Fibroblast Growth Factor/pharmacology;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Receptors, Nerve Growth Factor/*drug effects/metabolism}, Number = {1}, Organization = {Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {65-81.}, Title = {Retinoic acid and neurotrophins collaborate to regulate neurogenesis in adult-derived neural stem cell cultures}, Uuid = {2C8D170B-D877-4B0E-A18C-03B639004C7F}, Volume = {38}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10027563}} @article{Takahashi:1995, Abstract = {Neurons destined for the cerebral neocortex are formed in the pseudostratified ventricular epithelium (PVE) lining the ventricular cavity of the developing cerebral wall. The present study, based upon cumulative S-phase labeling with bromodeoxyuridine, is an analysis of cell cycle parameters of the PVE. It is undertaken in the dorsomedial cerebral wall of mouse embryos from the eleventh to the seventeenth gestational day (E11-E17, day of conception = E0) corresponding to the complete period of neuronogenesis. The growth fraction (fraction of cells in the population which is proliferating) is virtually 1.0 from E11 through E16. The length of the cell cycle increases from 8.1 to 18.4 hr, which corresponds to a sequence of 11 integer cell cycles over the course of neuronal cytogenesis in mice. The increase in the length of the cell cycle is due essentially to a fourfold increase in the length of G1 phase which is the only phase of the cell cycle which varies systematically. Thus, the G1 phase is most likely to be the phase of the cell cycle which is modulated by extrinsically and intrinsically acting mechanisms involved in the regulation of neuronal cytogenesis.}, Author = {Takahashi, T. and Nowakowski, R. S. and Caviness, V. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Embryonic and Fetal Development;Epithelium;Research Support, U.S. Gov't, P.H.S.;Cell Cycle;Research Support, U.S. Gov't, Non-P.H.S.;Mice;Animals;Cerebral Ventricles;Mice, Inbred Strains;Bromodeoxyuridine}, Medline = {95395589}, Month = {9}, Nlm_Id = {8102140}, Number = {9}, Organization = {Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.}, Pages = {6046-57}, Pubmed = {7666188}, Title = {The cell cycle of the pseudostratified ventricular epithelium of the embryonic murine cerebral wall}, Uuid = {5D68872E-541F-4423-B128-0742A44DEAA3}, Volume = {15}, Year = {1995}} @article{Takahashi:1995a, Abstract = {The present report is an analysis of the proliferative behavior of the secondary proliferative population (SPP) of the dorsomedial region of the embryonic mouse cerebral wall. It is based upon experiments undertaken on embryonic days 14-16 (E14-E16) and exploits methods in which proliferative cells are labeled in S phase with either or both bromodeoxyuridine and tritiated thymidine. The SPP, which arises from the PVE by E13, is principally the progenitor population to the neuroglial population of the mature neocortex and subjacent cerebral wall. By the end of E14 the SPP comes to be distributed diffusely from the outer margin of the ventricular zone throughout subventricular zone and intermediate zone. The length of the cell cycle of the SPP is constant at approximately 15 hr throughout this interval; thus, this population undergoes 1.6 cell cycles/24 hr or 3.2 cycles in the course of the 48 hr period, E14-E16. Over this 48 hr period, the SPP increases from 11\%to 35\%of the total proliferative population of the dorsomedial cerebral wall. The absolute size of the SPP increases nearly sixfold. With these values taken together it may be estimated that approximately 87\%of postmitotic cells of the SPP reenter S phase after each cell division in this interval which means that only approximately 13\%of the proliferative population exits the cycle. These findings illustrate the massive expansion of the SPP antecedent to the explosive diffusion of glial cells through the neocortex and subjacent cerebral wall as neuronal migration comes to completion and neocortical growth and differentiation accelerate.}, Author = {Takahashi, T. and Nowakowski, R. S. and Caviness, V. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Thymidine;Research Support, Non-U.S. Gov't;Embryonic and Fetal Development;S Phase;Research Support, U.S. Gov't, P.H.S.;Cell Division;Cell Cycle;Research Support, U.S. Gov't, Non-P.H.S.;Animals;Bromodeoxyuridine;Brain;Mice;24 Pubmed search results 2008}, Medline = {95395590}, Month = {9}, Nlm_Id = {8102140}, Number = {9}, Organization = {Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.}, Pages = {6058-68}, Pubmed = {7666189}, Title = {Early ontogeny of the secondary proliferative population of the embryonic murine cerebral wall}, Uuid = {E59F52BF-6524-4EEC-885D-CD2156382C5B}, Volume = {15}, Year = {1995}} @article{Takahashi:2007, Abstract = {Functional multineuron calcium imaging (fMCI) is a large-scale optical recording technique that monitors the spatiotemporal pattern of action potentials, all at once, from large neuron populations. fMCI has unique advantages, including: (i) simultaneous recording from >1000 neurons in a wide area, (ii) single-cell resolution, (iii) identifiable location of neurons and (iv) detection of non-active neurons during the observation period. We review herein the principle, history, utility and limitations of fMCI.}, Author = {Takahashi, Naoya and Sasaki, Takuya and Usami, Atsushi and Matsuki, Norio and Ikegaya, Yuji}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Synapses;research support, non-u.s. gov't;21 Neurophysiology;History, 20th Century;Calcium;21 Calcium imaging;Diagnostic Imaging;historical article;Nerve Net;Animals;History, 21st Century;24 Pubmed search results 2008;review;Neurons}, Month = {7}, Nlm_Id = {8500749}, Number = {3}, Organization = {Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan.}, Pages = {219-25}, Pii = {S0168-0102(07)00110-1}, Pubmed = {17418439}, Title = {Watching neuronal circuit dynamics through functional multineuron calcium imaging (fMCI)}, Uuid = {BD8EAEC5-3635-4CDE-8906-19E758729BFA}, Volume = {58}, Year = {2007}, url = {papers/Takahashi_NeurosciRes2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neures.2007.03.001}} @article{Takahashi:2003, Abstract = {The mechanisms underlying experience-dependent plasticity in the brain may depend on the AMPA subclass of glutamate receptors (AMPA-Rs). We examined the trafficking of AMPA-Rs into synapses in the developing rat barrel cortex. In vivo gene delivery was combined with in vitro recordings to show that experience drives recombinant GluR1, an AMPA-R subunit, into synapses formed between layer 4 and layer 2/3 neurons. Moreover, expression of the GluR1 cytoplasmic tail, a construct that inhibits synaptic delivery of endogenous AMPA-Rs during long-term potentiation, blocked experience-driven synaptic potentiation. In general, synaptic incorporation of AMPA-Rs in vivo conforms to rules identified in vitro and contributes to plasticity driven by natural stimuli in the mammalian brain. 1095-9203 Journal Article}, Author = {Takahashi, T. and Svoboda, K. and Malinow, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Science}, Keywords = {Long-Term Potentiation;Touch;Recombinant Fusion Proteins/metabolism;Electrophysiology;Animals;*Neuronal Plasticity;*Synaptic Transmission;Rats;Somatosensory Cortex/*metabolism/virology;Vibrissae/physiology;Patch-Clamp Techniques;Synapses/*metabolism;Support, Non-U.S. Gov't;Gene Transfer Techniques;Neurons/*metabolism/virology;Support, U.S. Gov't, P.H.S.;K pdf;Receptors, AMPA/genetics/*metabolism;Sindbis Virus/genetics;16 Barrels}, Number = {5612}, Organization = {Jones Laboratory, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.}, Pages = {1585-8}, Title = {Experience strengthening transmission by driving AMPA receptors into synapses}, Uuid = {1388F444-2DFC-495F-88E3-63BA7D3AAFF3}, Volume = {299}, Year = {2003}, url = {papers/Takahashi_Science2003.pdf}} @article{Takasawa:2002, Abstract = {Recent studies demonstrated that neurogenesis in the adult hippocampus increased after transient global ischemia; however, the molecular mechanism underlying increased neurogenesis after ischemia remains unclear. The finding that proliferation of progenitor cells occurred at least a week after ischemic insult suggests that the stimulus was not an ischemic insult to progenitor cells. To clarify whether focal ischemia increases the rate of neurogenesis in the remote area, the authors examined the contralateral hemisphere in rats subjected to permanent occlusion of the middle cerebral artery. In the subgranular zone of the hippocampal dentate gyrus, the numbers of bromodeoxyuridine (BrdU)-positive cells increased approximately sixfold 7 days after ischemia. In double immunofluorescence staining, more than 80\%of newborn cells expressed Musashi1, a marker of neural stem/progenitor cells, but only approximately 10\%of BrdU-positive cells expressed glial fibrillary acidic protein (GFAP), a marker of astrocytes. The number of BrdU-positive cells markedly decreased 28 days after BrdU administration after ischemia, but it was still elevated compared with that of sham-operated rats. In double immunofluorescence staining, 80\%of newborn cells expressed NeuN, a marker of differentiated neurons, and 10\%of BrdU-positive cells expressed GFAP. However, in the other areas of the contralateral hemisphere including the rostral subventricular zone, the number of BrdU-positive cells remained unchanged. These results showed that focal ischemia stimulated the proliferation of neuronal progenitor cells, but did not support survival of newborn cells in the contralateral hippocampus. 0271-678x Journal Article}, Author = {Takasawa, K. and Kitagawa, K. and Yagita, Y. and Sasaki, T. and Tanaka, S. and Matsushita, K. and Ohstuki, T. and Miyata, T. and Okano, H. and Hori, M. and Matsumoto, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Cereb Blood Flow Metab}, Keywords = {Brain/*pathology;Dentate Gyrus/*pathology;Laterality;D abstr;Ischemic Attack, Transient/*pathology;Middle Cerebral Artery;Rats;Stem Cells/*cytology/*pathology;Rats, Wistar;Cell Survival;Hippocampus/*pathology;06 Adult neurogenesis injury induced;Support, Non-U.S. Gov't;Brain Ischemia/pathology;Animals;Neurons/*pathology;Male}, Number = {3}, Organization = {Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.}, Pages = {299-307}, Pubmed = {11891435}, Title = {Increased proliferation of neural progenitor cells but reduced survival of newborn cells in the contralateral hippocampus after focal cerebral ischemia in rats}, Uuid = {7B974738-EC81-11DA-8605-000D9346EC2A}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11891435}} @article{Takasu:2002, Abstract = {Protein-protein interactions and calcium entry through the N-methyl-d-aspartate (NMDA)-type glutamate receptor regulate synaptic development and plasticity in the central nervous system. The EphB receptor tyrosine kinases are localized at excitatory synapses where they cluster and associate with NMDA receptors. We identified a mechanism whereby EphBs modulate NMDA receptor function. EphrinB2 activation of EphB in primary cortical neurons potentiates NMDA receptor-dependent influx of calcium. Treatment of cells with ephrinB2 led to NMDA receptor tyrosine phosphorylation through activation of the Src family of tyrosine kinases. These ephrinB2-dependent events result in enhanced NMDA receptor-dependent gene expression. Our findings indicate that ephrinB2 stimulation of EphB modulates the functional consequences of NMDA receptor activation and suggest a mechanism whereby activity-independent and activity-dependent signals converge to regulate the development and remodeling of synaptic connections. 1095-9203 Journal Article}, Author = {Takasu, M. A. and Dalva, M. B. and Zigmond, R. E. and Greenberg, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Science}, Keywords = {Ephrin-B2;Cell Line;Models, Neurological;Receptor, EphB4;Animals;Cells, Cultured;Receptor Protein-Tyrosine Kinases/chemistry/genetics/*metabolism;Recombinant Fusion Proteins/metabolism/pharmacology;04 Adult neurogenesis factors;Proto-Oncogene Proteins/metabolism;Glutamic Acid/metabolism;Membrane Proteins/*metabolism/pharmacology;Receptors, Eph Family;Genes, Reporter;Signal Transduction;Transcription, Genetic;Phosphotyrosine/metabolism;src-Family Kinases/metabolism;Brain-Derived Neurotrophic Factor/pharmacology;Neurons/*metabolism;Support, U.S. Gov't, P.H.S.;Mutation;DNA-Binding Protein, Cyclic AMP-Responsive/metabolism;Immunoglobulins, Fc;Rats;Receptors, N-Methyl-D-Aspartate/genetics/*metabolism;Calcium/*metabolism;Cerebral Cortex/cytology/embryology;Support, Non-U.S. Gov't;Synapses/metabolism;Phosphorylation;*Gene Expression Regulation;Human;C abstr}, Number = {5554}, Organization = {Division of Neuroscience, Children's Hospital, and the Department of Neurobiology, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {491-5}, Pubmed = {11799243}, Title = {Modulation of NMDA receptor-dependent calcium influx and gene expression through EphB receptors}, Uuid = {BE724942-26D0-4935-87F1-AB34F3C53591}, Volume = {295}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11799243}} @article{Takemura:2002, Abstract = {BACKGROUND: Glial fibrillary acidic protein (GFAP) is the principal component of intermediate filaments (IFs) in mature astrocytes in the central nervous system (CNS). Like other IF proteins, GFAP has multiple phosphorylation sites in the N-terminal head domain. The distribution of phospho-GFAP in vivo has not been elucidated. RESULTS: We generated Gfap(hwt) knock-in mice, in which the coding region for the head domain of GFAP is replaced with the corresponding human sequence. In combination with a series of monoclonal antibodies (mAbs) reactive to human phospho-GFAP, we visualized the distribution of phospho-GFAP in vivo in mice. GFAP phosphorylated at Thr7, Ser8 and/or Ser13 increased postnatally in the CNS of these mice. Limited populations of GFAP-positive astrocytes were labelled with anti-phospho-GFAP mAbs in most brain areas, whereas almost all the astrocytes in the optic nerve and spinal cord were labelled. Astrocytes in the subventricular zone and rostral migratory stream preferentially contained phospho-GFAP. In a cold injury model of the cerebral cortex, we detected phospho-GFAP in reactive astrocytes at 2-3 weeks after the injury. CONCLUSIONS: Phospho-GFAP provides a molecular marker indicating the heterogeneity of astrocytes, and Gfap(hwt) knock-in mice will aid in monitoring intracellular conditions of astrocytes, under various conditions. Our results suggest that the phosphorylation of GFAP plays a role in non-dividing astrocytes in vivo. 1356-9597 Journal Article}, Author = {Takemura, M. and Nishiyama, H. and Itohara, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Genes Cells}, Keywords = {Organ Specificity;Glial Fibrillary Acidic Protein/genetics/*metabolism;Central Nervous System/*metabolism;G abstr;Immunohistochemistry;Animals, Genetically Modified;11 Glia;Astrocytes/*metabolism;Animals;Support, Non-U.S. Gov't;Mice;Phosphotransferases/*metabolism;Phosphorylation}, Number = {3}, Organization = {Laboratory for Behavioural Genetics, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako 351-0198, Japan.}, Pages = {295-307}, Pubmed = {11918673}, Title = {Distribution of phosphorylated glial fibrillary acidic protein in the mouse central nervous system}, Uuid = {6DD56C00-56B7-4887-A0FD-D9900D524E00}, Volume = {7}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11918673}} @article{Takeuchi:2005, Abstract = {Recent studies suggest that excitotoxicity may contribute to neuronal damage in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Activated microglia have been observed around degenerative neurons in these diseases, and they are thought to act as effector cells in the degeneration of neural cells in the central nervous system. Neuritic beading, focal bead-like swellings in the dendrites and axons, is a neuropathological sign in epilepsy, trauma, ischemia, aging and neurodegenerative diseases. Previous reports showed that neuritic beading is induced by various stimuli including glutamate or nitric oxide and is a neuronal response to harmful stimuli. However, the precise physiologic significance of neuritic beading is unclear. We provide evidence that neuritic beading induced by activated microglia is a feature of neuronal cell dysfunction toward neuronal death, and the neurotoxicity of activated microglia is mediated through N-methyl-D-aspartate (NMDA) receptor signaling. Neuritic beading occurred concordant with a rapid drop in intracellular ATP levels and preceded neuronal death. The actual neurite beads consisted of collapsed cytoskeletal proteins and motor proteins arising from impaired neuronal transport secondary to cellular energy loss. The drop in intracellular ATP levels was due to the inhibition of mitochondrial respiratory chain complex IV activity downstream of NMDA receptor signaling. Blockage of NMDA receptors nearly completely abrogated mitochondrial dysfunction and neurotoxicity. Thus, neuritic beading induced by activated microglia occurs through NMDA receptor signaling and represents neuronal cell dysfunction preceding neuronal death. Blockage of NMDA receptors may be an effective therapeutic approach for neurodegenerative diseases.}, Author = {Takeuchi, and Mizuno, and Zhang, and Wang, and Kawanokuchi, and Kuno, and Suzumura,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {2985121R}, Organization = {Department of Neuroimmunology, Nagoya University Research Institute of Environmental Medicine, Nagoya 464-8601.}, Pii = {M413863200}, Pubmed = {15640150}, Title = {Neuritic beading induced by activated microglia is an early feature of neuronal dysfunction toward neuronal death by inhibition of mitochondrial respiration and axonal transport}, Uuid = {3AE25662-A663-4495-AACE-C5159906F3F0}, Year = {2005}, url = {papers/Takeuchi_JBiolChem2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1074/jbc.M413863200}} @article{Takeuchi:2006, Abstract = {MAM (meprin/A5 protein/receptor protein tyrosine phosphatase mu) domain glycosylphosphatidylinositol anchor 1 (MDGA1), a unique cell surface glycoprotein, is similar to Ig-containing cell adhesion molecules that influence neuronal migration and process outgrowth. We show in postnatal mice that MDGA1 is expressed by layer 2/3 neurons throughout the neocortex. During development, MDGA1 is expressed in patterns consistent with its expression by migrating layer 2/3 neurons, suggesting a role for MDGA1 in controlling their migration and settling in the superficial cortical plate. To test this hypothesis, we performed loss-of-function studies using RNA interference (RNAi) targeting different sequences of mouse MDGA1. RNAi or empty vectors were coelectroporated with an enhanced green fluorescent protein reporter in utero into the lateral ventricle at embryonic day 15.5 to transfect progenitors of superficial layer neurons; the distributions of transfected neurons were analyzed late on postnatal day 0. We found a direct correlation between effectiveness of an RNAi in suppressing MDGA1 expression and disrupting migration of superficial layer neurons. An RNAi with no effect on MDGA1 expression has no effect on the migration. In contrast, an RNAi that suppresses MDGA1 expression also blocks proper migration of transfected superficial layer neurons, with essentially all transfected cells found deep in the cortical plate or beneath it. This migration defect is rescued by cotransfection of a rat MDGA1 expression construct along with the effective RNAi, confirming that the RNAi effect is specific to diminishing mouse MDGA1 expression. RNAi transfections of deep layer neurons that do not express MDGA1 do not significantly affect their migration. We conclude that MDGA1 acts cell autonomously to control the migration of MDGA1-expressing superficial layer cortical neurons.}, Author = {Takeuchi, Akihide and O'Leary, Dennis D. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {17}, Organization = {Molecular Neurobiology Laboratory, The Salk Institute, La Jolla, California 92037, USA.}, Pages = {4460-4}, Pii = {26/17/4460}, Pubmed = {16641224}, Title = {Radial migration of superficial layer cortical neurons controlled by novel Ig cell adhesion molecule MDGA1}, Uuid = {35D564D0-E31B-4E0D-ABDC-2929062E5766}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4935-05.2006}} @article{Takeuchi:2001, Abstract = {In a previous study, we have demonstrated that damaged neurons within a boundary area around necrosis fall into delayed neuronal death owing to the cytotoxic effect of microglial nitric oxide (NO), and these neurons are finally eliminated by activated microglia. In this process, microglia are activated to release NO, increase in number, and accumulate toward the damaged area. In this study, we investigated the expression of macrophage colony-stimulating factor (M-CSF, also called colony stimulating factor-1; CSF-1) and other cytokines, which are reported to relate to activation, proliferation, or migration of microglia. The mRNA of M-CSF arose biphasically from 30 min to 1 hr and from 6 to 72 hr after the injury, as demonstrated by semiquantitative RT-PCR. However, another cytokine of granulocyte-macrophage CSF (GM-CSF) or interleukin-3 (IL-3), which causes proliferation of microglia in vitro, was not detected. From immunohistochemical studies, positive staining of M-CSF was observed mainly in neuron-specific enolase (NSE)-positive cells from 1 to 12 hr after the injury, and after that M-CSF became positive in Griffonia simplicifolia isolectin-B4 (GSA-I-B4)-positive cells from 24 to 72 hr in the boundary area around necrosis. These results suggest that neurons around the damaged area express M-CSF in the early phase after injury, which may initially activate microglia, and these activated microglia also express M-CSF later, causing further proliferation or migration of microglia themselves to eliminate damaged neurons or necrotic brain tissue.}, Author = {Takeuchi, A. and Miyaishi, O. and Kiuchi, K. and Isobe, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Nerve Degeneration;Astrocytes;Stereotaxic Techniques;Encephalitis;Rats;Ethanol;Animals;Microglia;Central Nervous System Depressants;RNA, Messenger;Not relevant;11 Glia;Support, Non-U.S. Gov't;Fusobacterium Infections;Neurons;Macrophage Colony-Stimulating Factor;Gene Expression;Nitric Oxide}, Medline = {21326332}, Month = {7}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Basic Gerontology, National Institute for Longevity Sciences, Oobu-city, Aichi, Japan.}, Pages = {38-44}, Pubmed = {11433427}, Title = {Macrophage colony-stimulating factor is expressed in neuron and microglia after focal brain injury}, Uuid = {9466DE13-65EB-4E2B-8F7C-2D097CBA0535}, Volume = {65}, Year = {2001}, url = {papers/Takeuchi_JNeurosciRes2001.pdf}} @article{Taleisnik:1981, Author = {Taleisnik, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0361-7742}, Journal = {Prog Clin Biol Res}, Keywords = {24 Pubmed search results 2008;Electrochemistry;Research Support, Non-U.S. Gov't;Gonadotropins;Neurotransmitters;Neural Pathways;Humans;Cerebral Cortex;review;Frontal Lobe}, Medline = {82106093}, Nlm_Id = {7605701}, Pages = {249-57}, Pubmed = {6119701}, Title = {Role of the frontal lobe cortex in the regulation of gonadotropin secretion}, Uuid = {3A0C2937-BDFD-4794-98F1-39384857A262}, Volume = {74}, Year = {1981}} @article{Tamaki:2002, Abstract = {Direct isolation of human central nervous system stem cells (CNS-SC) based on cell surface markers yields a highly purified stem cell population that can extensively expand in vitro and exhibit multilineage differentiation potential both in vitro and in vivo. The CNS-SC were isolated from fetal brain tissue using the cell surface markers CD133(+), CD34(-), CD45(-), and CD24(-/lo) (CD133(+) cells). Fluorescence-activated cell sorted (FACS) CD133(+) cells continue to expand exponentially as neurospheres while retaining multipotential differentiation capacity for >10 passages. CD133(-), CD34(-), and CD45(-) sorted cells (approximately 95\%of total fetal brain tissue) fail to initiate neurospheres. Neurosphere cells transplanted into neonatal immunodeficient NOD-SCID mice proliferated, migrated, and differentiated in a site-specific manner. However, it has been difficult to evaluate human cell engraftment, because many of the available monoclonal antibodies against neural cells (beta-tubulin III and glial fibrillary acidic protein) are not species specific. To trace the progeny of human cells after transplantation, CD133(+)-derived neurosphere cells were transduced with lentiviral vectors containing enhanced green fluorescent protein (eGFP) expressed downstream of the phosphoglycerate kinase promoter. After transduction, GFP(+) cells were enriched by FACS, expanded, and transplanted into the lateral ventricular space of neonatal immunodeficient NOD-SCID brain. The progeny of transplanted cells were detected by either GFP fluorescence or antibody against GFP. GFP(+) cells were present in the subventricular zone-rostral migrating stream, olfactory bulb, and hippocampus as well as nonneurogenic sites, such as cerebellum, cerebral cortex, and striatum. Antibody against GFP revealed that some of the cells displayed differentiating dendrites and processes with neurons or glia cells. Thus, marking human CNS-SC with reporter genes introduced by lentiviral vectors is a useful tool with which to characterize migration and differentiation of human cells in this mouse transplantation model.}, Author = {Tamaki, Stanley and Eckert, Karl and He, Dongping and Sutton, Richard and Doshe, Monika and Jain, Gitanjali and Tushinski, Robert and Reitsma, Michael and Harris, Brent and Tsukamoto, Ann and Gage, Fred and Weissman, Irving and Uchida, Nobuko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cell Differentiation;Transduction, Genetic;Mice, Inbred NOD;Corpus Striatum;Animals;Brain Tissue Transplantation;Humans;Cell Separation;Stem Cell Transplantation;Lentivirus;Indicators and Reagents;Mice, SCID;Hippocampus;Cell Movement;Green Fluorescent Proteins;Fetal Tissue Transplantation;11 Glia;Genetic Vectors;Injections, Intraventricular;Olfactory Pathways;Neurons;Mice;Cell Division;Luminescent Proteins;Stem Cells;Corpus Callosum}, Medline = {22194586}, Month = {9}, Nlm_Id = {7600111}, Number = {6}, Organization = {StemCells, Inc., Palo Alto, California.}, Pages = {976-86}, Pubmed = {12205691}, Title = {Engraftment of sorted/expanded human central nervous system stem cells from fetal brain}, Uuid = {F22E1447-6E7A-4E23-B983-8F308A7FD6D3}, Volume = {69}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10412}} @article{Tamamaki:2001, Abstract = {Neocortical neurons are produced by cell division of neural stem cells in the ventricular zone of the cerebral cortex. We investigated the production of neurons by infecting neuroepithelial cells with a modified GFP-recombinant adenovirus. The adenovirus DNA is inherited by only one daughter cell at each cell division and travels one way from the progenitor to the progeny. Since the ventricular zone (VZ) of the embryo neocortex expressed an adenovirus receptor, CAR ubiquitously, morphology and cell-lineage of cells in the VZ could be revealed by the adenovirus infection. Radial glias, cells with a bipolar shape, and spherical cells were found as modified-GFP-positive (mGFP+) in the VZ. The bipolar cells (radial cells) had a radial process not in contact with the pia mater and a growth-cone-like structure at the edge of their radial process, while the radial glias had a process spanning all the cortical layers. Ten hours after viral infection, most mGFP+ cells were radial cells. In the following 8 h, the percentage of mGFP+ radial glias in mGFP+ neocortical cells increased from 18 to 50\%, while that in radial/spherical cells decreased from 75 to 19\%. The radial glias often divided asymmetrically and produced spherical cells and neuronal precursors. The spherical cells seemed to become radial cells by extending a radial process. The spherical cells, radial cells and radial glias seemed to constitute a proliferating cell cycle during which postmitotic neuronal precursors are produced. The neuronal precursors that inherited the radial processes migrated radially and developed into neocortical neurons. Four days after the viral infection, 97\%of mGFP+ cells were neocortical neurons. Here, we propose that the radial glia is a progenitor of neocortical neurons, and that a significant number of radially migrating neurons is guided by their own radial processes connected to the pia mater.}, Author = {Tamamaki, N. and Nakamura, K. and Okamoto, K. and Kaneko, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Fetus;Cell Differentiation;Animals;Aging;Indicators and Reagents;Cell Movement;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Genetic Vectors;Cell Lineage;Cerebral Cortex;Neurons;Neuroglia;Receptors, Virus;Mice;Cell Division;Microscopy, Electron;Growth Cones;Stem Cells;Luminescent Proteins;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {21427498}, Month = {9}, Nlm_Id = {8500749}, Number = {1}, Organization = {Department of Morphological Brain Science, Graduate School of Medicine, Kyoto University, Yoshida Konoecho, Sakyoku, 606-8501, Kyoto, Japan. tamamaki\@mbs.med.kyoto-u.ac.jp}, Pages = {51-60}, Pii = {S0168010201002590}, Pubmed = {11535293}, Title = {Radial glia is a progenitor of neocortical neurons in the developing cerebral cortex}, Uuid = {A7D165DA-76BE-445F-A376-5B8632C9B1FD}, Volume = {41}, Year = {2001}} @article{Tamura:2007, Abstract = {In the adult mammalian brain, multipotent stem or progenitor cells involved in reproduction of neurons and glial cells have been well investigated only in very restricted regions; the subventricular zone of the lateral ventricle and the dentate gyrus in the hippocampal formation. In the neocortex, a series of in vitro studies has suggested the possible existence of neural progenitor cells possessing neurogenic and/or gliogenic potential in adult mammals. However, the cellular properties of the cortical progenitor cells in vivo have not been fully elucidated. Using 5'-bromodeoxyuridine labeling and immunohistochemical analysis of cell differentiation markers, we found that a subpopulation of NG2-immunopositive cells co-expressing doublecortin (DCX), an immature neuron marker, ubiquitously reside in the adult rat neocortex. Furthermore, these cells are the major population of proliferating cells in the region. The DCX(+)/NG2(+) cells reproduced the same daughter cells, or differentiated into DCX(+)/NG2(-) (approximately 1\%) or DCX(-)/NG2(+) (approximately 10\%) cells within 2 weeks after cell division. The DCX(+)/NG2(-) cells were also immunopositive for TUC-4, a neuronal linage marker, suggesting that these cells were committed to neuronal cell differentiation, whereas the DCX(-)/NG2(+) cells showed faint immunoreactivity for glutathione S-transferase (GST)-pi, an oligodendrocyte lineage marker, in the cytoplasm, suggesting glial cell lineage, and thereafter the cells differentiated into NG2(-)/GST-pi(+) mature oligodendrocytes after a further 2 weeks. These findings indicate that DCX(+)/NG2(+) cells ubiquitously exist as 'multipotent progenitor cells' in the neocortex of adult rats.}, Author = {Tamura, Yasuhisa and Kataoka, Yosky and Cui, Yilong and Takamori, Yasuharu and Watanabe, Yasuyoshi and Yamada, Hisao}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Microtubule-Associated Proteins;Cell Differentiation;Animals;Rats;Multipotent Stem Cells;Phosphopyruvate Hydratase;Models, Biological;Neocortex;Cell Count;research support, non-u.s. gov't;Time Factors;Neuropeptides;Male;01 Adult neurogenesis general;Glutathione Transferase;Versicans;Immunohistochemistry;24 Pubmed search results 2008;Bromodeoxyuridine;Nerve Tissue Proteins}, Month = {6}, Nlm_Id = {8918110}, Number = {12}, Organization = {Department of Anatomy and Cell Science, KMU 21C COE Project, Kansai Medical University, Osaka, Japan.}, Pages = {3489-98}, Pii = {EJN5617}, Pubmed = {17610569}, Title = {Multi-directional differentiation of doublecortin- and NG2-immunopositive progenitor cells in the adult rat neocortex in vivo}, Uuid = {2B39259E-FB93-4DB5-A031-AF1DA7DD5477}, Volume = {25}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2007.05617.x}} @article{Tanaka:2006a, Abstract = {The doublecortin (Dcx) and doublecortin-like kinase 1 (Dclk) genes are developmentally expressed neuronal microtubule-associated proteins. Humans with DCX mutations show a severe defect in hippocampal development, but targeted deletion in mouse shows only a defect in pyramidal neuron lamination. There is significant sequence overlap between Dcx and Dclk, suggesting functional redundancy. Here we show that the two genes display overlapping expression patterns in developing mouse hippocampus. Targeted deletion of Dclk shows no appreciable developmental defect in the hippocampus, but removal of both genes shows severe hippocampal lamination defects involving the entire cornu ammonis and dentate gyrus fields that mimic the human phenotype. These results suggest these genes are partially functionally redundant in the formation of the murine hippocampus.}, Author = {Tanaka, Teruyuki and Koizumi, Hiroyuki and Gleeson, Joseph G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Microtubule-Associated Proteins;Cell Differentiation;Animals;Aging;Cell Movement;Hippocampus;Protein-Serine-Threonine Kinases;research support, non-u.s. gov't;Neuropeptides;Animals, Newborn;Nerve Net;Mice, Knockout;Neurons;Cell Aggregation;Organogenesis;research support, n.i.h., extramural;Body Patterning;Mice;24 Pubmed search results 2008;in vitro}, Month = {7}, Nlm_Id = {9110718}, Organization = {Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, CA, USA.}, Pages = {i69-73}, Pii = {16/suppl_1/i69}, Pubmed = {16766710}, Title = {The doublecortin and doublecortin-like kinase 1 genes cooperate in murine hippocampal development}, Uuid = {DFBB8848-D8DB-46D9-9EF7-66355ED1F17E}, Volume = {16 Suppl 1}, Year = {2006}, url = {papers/Tanaka_CerebCortex2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhk005}} @article{Tanaka:2002a, Abstract = {The mrf-1 gene has been isolated from microglia exposed to cultured cerebellar granule neurons undergoing apoptosis. We have shown that mrf-1 is upregulated in response to neuronal death and degeneration both in vitro and in vivo. However, the exact role of MRF-1 remains unknown. Here we show that MRF-1 is released from cultured rat microglia, and its release is greatly enhanced under inflammatory conditions. When microglia were treated with ATP, the amount of MRF-1 that was released increased 10-fold compared to the basal level of release. Enhanced MRF-1 release was induced within 10 min and peaked within 1 h; after approximately 4 h, the MRF-1 release had returned to normal. MRF-1 release was stimulated by 2-methyl-thio-ATP (five-fold) and a P2X(7) selective agonist, 2'- and 3'-O-(4-benzoylbenzoyl)-ATP (ten-fold). Moreover, the ATP-stimulated MRF-1 release was inhibited by a P2X(7) selective antagonist, oxidized ATP (oATP), and also under a Ca(2+)-free condition. These results indicate that the effects of ATP are dependent on Ca(2+) influx through P2X(7) receptors. MRF-1 release was enhanced by Ca(2+)-ionophore A23187 (sixfold), thapsigargin (threefold); however, it was not enhanced by glutamate or lipopolysaccharide. Moreover, a platelet-activating factor enhanced microglial MRF-1 release in a dose-dependent manner. We also showed that a conditioned medium from cerebellar granule neurons undergoing apoptosis markedly increased MRF-1 release from microglia; that effect was significantly inhibited by oATP. These results indicate that selective inflammatory stimulations, including ATP and PAF, enhance MRF-1 release from microglia through a Ca(2+)-dependent mechanism and suggest that MRF-1 may play a role in cell-cell interactions under inflammatory conditions.}, Author = {Tanaka, Shuuitsu and Koike, Tatsuro}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Calcium Signaling;Animals;Cells, Cultured;Encephalitis;Rats;Enzyme Inhibitors;Up-Regulation;Chemotaxis;Microglia;Cell Communication;Rats, Sprague-Dawley;Culture Media, Conditioned;11 Glia;Ionophores;Adenosine Triphosphate;Animals, Newborn;Support, Non-U.S. Gov't;Platelet Activating Factor;Neurons;Inflammation Mediators;Gliosis;Nerve Tissue Proteins;Receptors, Purinergic P2}, Medline = {22307125}, Month = {12}, Nlm_Id = {8806785}, Number = {3}, Organization = {Molecular Neurobiology Laboratory, Division of Biological Sciences, Graduate School of Science, Hokkaido University, Sapporo, Japan. shtanaka\@sci.hokudai.ac.jp}, Pages = {360-71}, Pubmed = {12420315}, Title = {Selective inflammatory stimulations enhance release of microglial response factor (MRF)-1 from cultured microglia}, Uuid = {583C5467-7ACD-4493-8201-9E431D77D847}, Volume = {40}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10142}} @article{Tanaka:1999, Abstract = {Notch family molecules are thought to be negative regulators of neuronal differentiation in early brain development. After expression in the embryonic period, Notch2 continues to be expressed postnatally in the specific regions in the rodent brain. Here, we examined Notch2 expression in the postnatal mouse brain using lacZ knockin animals at the Notch2 locus. Notch2 expression was observed in the developing cerebellum and hippocampus, characteristic regions where neurogenesis persists after birth. Double staining of sections revealed that Notch2 was expressed by Bergmann glia in the cerebellum, radial glia in the hippocampus, and some astrocytes in both regions. Notch2 expression by glial cells was clearly confirmed in dissociated cell cultures. Interestingly, neocortical glia, many of which did not express Notch2 in vivo, did express Notch2 in a dissociated culture condition. The triple staining of dissociated cell cultures revealed that stronger Notch2 expression correlated with the immature type of glial gene expressions: stronger vimentin and weaker glial fibrillary acidic protein expressions. In addition, Notch2 expression correlated with the incorporation of bromodeoxyuridine both in vivo and in vitro. Thus, these findings demonstrate that Notch2 is expressed not only by neuronal cells in the embryonic brain, but also by glial cells in the postnatal brain, and that its expression negatively correlates with glial differentiation, proposing its novel function as a negative regulator of glial differentiation in mammalian brain development.}, Author = {Tanaka, M. and Kadokawa, Y. and Hamada, Y. and Marunouchi, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurobiol}, Keywords = {G;Cell Differentiation;Aging;Cerebellum/cytology/growth &development/metabolism;Brain/cytology/growth &development/*metabolism;*Gene Expression Regulation, Developmental;Female;Animal;Glial Fibrillary Acidic Protein/analysis;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;beta-Galactosidase/genetics;Crosses, Genetic;Receptors, Cell Surface/analysis/*genetics;Male;Neuroglia/cytology/*physiology;In Situ Hybridization;Support, Non-U.S. Gov't;Mice}, Number = {4}, Organization = {Division of Cell Biology, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi 470-1192, Japan.}, Pages = {524-39.}, Title = {Notch2 expression negatively correlates with glial differentiation in the postnatal mouse brain}, Uuid = {B7CC0E42-C7B1-487B-A7D3-82B10561BD8F}, Volume = {41}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10590176}} @article{Tanaka:2002, Abstract = {An ischemia-induced gene was screened using a differential display technique in mouse transient forebrain ischemia. One of the ischemia-responsive clones was found to encode mouse hsp40. HSP40 has a critical regulatory function in the HSC70 ATPase activity. Expression of hsp40 mRNA was low in the nonischemic mouse hippocampus, but it was significantly upregulated 4 hr after ischemia by Northern blot analysis. In situ hybridization analysis revealed hsp40 mRNA induction in the neuron. HSP40 protein expression was also enhanced in the pyramidal and dentate granular neurons from 2 to 4 days after ischemia. The temporal expression and distribution profile of HSC70 protein was similar to that of HSP40, and both proteins were colocalized in ischemic hippocampal neurons. In the gerbil transient forebrain ischemia model, both HSP40 and HSC70 proteins were expressed strongly in ischemia-resistant CA3 neurons and dentate granule cells 1 day after 5 min ischemia, but were not expressed in vulnerable CA1 neurons. However, both proteins were in parallel expressed in the tolerance-acquired CA1 neurons. Based on the current observation that both HSP40 and HSC70 proteins were synergistically expressed in the ischemia-resistant and tolerance-acquired neurons, cochaperone HSP40 may play a significant role against postischemic neuronal response and lead to cell survival through interaction with simultaneously induced HSC70. 21624013 0360-4012 Journal Article}, Author = {Tanaka, S. and Kitagawa, K. and Ohtsuki, T. and Yagita, Y. and Takasawa, K. and Hori, M. and Matsumoto, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurosci Res}, Keywords = {Up-Regulation/genetics;Neurons/*metabolism/pathology;Gene Expression Regulation/physiology;Gerbillinae;*Ischemic Preconditioning;Hippocampus/*metabolism/pathology/physiopathology;Heat-Shock Proteins/*genetics/metabolism;Nerve Degeneration/genetics/metabolism/physiopathology;Animal;C abstr;Mice, Inbred C57BL;Disease Models, Animal;Heat-Shock Proteins 70/*genetics/metabolism;Cell Survival/genetics;Reperfusion Injury/*genetics/metabolism/physiopathology;Male;Support, Non-U.S. Gov't;Brain Ischemia/*genetics/metabolism/physiopathology;04 Adult neurogenesis factors;Mice;Immunohistochemistry;RNA, Messenger/metabolism}, Number = {1}, Organization = {Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan. brain\@medone.med.osaka-u.ac.jp}, Pages = {37-47}, Pubmed = {11754079}, Title = {Synergistic induction of HSP40 and HSC70 in the mouse hippocampal neurons after cerebral ischemia and ischemic tolerance in gerbil hippocampus}, Uuid = {BD6D4C61-6613-43F1-94E4-ACF5937BA88D}, Volume = {67}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11754079}} @article{Tanaka:2006, Abstract = {We used lipopolysaccharide (LPS) to activate microglia that play an important role in the brain immune system. LPS injected into the rat hippocampus CA1 region activated microglial cells resulting in an increased production of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha in the hippocampus during the initial stage of treatment. Immunostaining for IL-1beta was increased at 6 hr after LPS injection. IL-1beta-immunopositive cells were co-localized with immunostaining for CD11b. Subacute treatment with LPS by the same route for 5 days caused long-term activation of microglia and induced learning and memory deficits in animals when examined with a step-through passive avoidance test, but histochemical analysis showed that neuronal cell death was not observed under these experimental conditions. The increased expression of the heme oxygenase-1 (HO-1) gene, an oxidative stress maker, was observed. However, the genetic expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, decreased during the course of LPS treatment. We found decreases in [(3)H]MK801 binding in the hippocampus CA1 region by LPS-treatment for 5 days. The data shows that glutamatergic transmission was attenuated in the LPS-treated rats. These results suggest that long-term activation of microglia induced by LPS results in a decrease of glutamatergic transmission that leads to learning and memory deficits without neuronal cell death. The physiologic significance of these findings is discussed. (c) 2006 Wiley-Liss, Inc.}, Author = {Tanaka, and Ide, and Shibutani, and Ohtaki, and Numazawa, and Shioda, and Yoshida,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {11 Glia}, Month = {1}, Nlm_Id = {7600111}, Organization = {Department of Biochemical Toxicology, School of Pharmaceutical Sciences.}, Pubmed = {16429444}, Title = {Lipopolysaccharide-induced microglial activation induces learning and memory deficits without neuronal cell deathin rats}, Uuid = {01D200C6-4B27-4416-BC9E-21349BCF7F9C}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20752}} @article{Tanaka:2003, Abstract = {Brain ischemia induces a marked response of resident microglia and hematopoietic cells including monocytes/macrophages. The present study was designed to assess the distribution of microglia/macrophages in cerebral ischemia using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). At 24 h after middle cerebral artery occlusion (MCAO), many round-shaped EGFP-positive cells migrated to the ischemic core and peri-infarct area. At 48-72 h after MCAO, irregular round- or oval-shaped EGFP/ionized calcium-binding adapter molecule 1 (Iba 1)-positive cells increased in the transition zone, while many amoeboid-shaped or large-cell-body EGFP/Iba 1-positive cells were increased in number in the innermost area of ischemia. At 7 days after MCAO, many process-bearing ramified shaped EGFP/Iba 1-positive cells were detected in the transition to the peri-infarct area, while phagocytic cells were distributed in the transition to the core area of the infarction. The distribution of these morphologically variable EGFP/Iba 1-positive cells was similar up to 14 days from MCAO. The present study directly showed the migration and distribution of bone marrow-derived monocytes/macrophages and the relationship between resident microglia and infiltrated hematogenous element in ischemic mouse brain. It is important to study the distribution of intrinsic and extrinsic microglia/macrophage in ischemic brain, since such findings may allow the design of appropriate gene-delivery system using exogenous microglia/macrophages to the ischemic brain area.}, Author = {Tanaka, R. and Komine-Kobayashi, M. and Mochizuki, H. and Yamada, M. and Furuya, T. and Migita, M. and Shimada, T. and Mizuno, Y. and Urabe, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Microtubule-Associated Proteins;Animals;Macrophages;Chimera;Whole-Body Irradiation;Comparative Study;Infarction, Middle Cerebral Artery;Microglia;Cell Count;Mice, Transgenic;Cell Movement;11 Glia;Green Fluorescent Proteins;Time Factors;Immunosuppressive Agents;Bone Marrow;Fluorouracil;Calcium-Binding Proteins;Brain Ischemia;Transplants;Mice;Luminescent Proteins;Central Nervous System;Immunohistochemistry;Dose-Response Relationship, Radiation;Research Support, Non-U.S. Gov't}, Medline = {22506166}, Nlm_Id = {7605074}, Number = {3}, Organization = {Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.}, Pages = {531-9}, Pii = {S0306452202009545}, Pubmed = {12617960}, Title = {Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia}, Uuid = {7E8946AA-A893-411B-BCA0-24D6462F6192}, Volume = {117}, Year = {2003}} @article{Tanaka:2004a, Abstract = {BACKGROUND AND PURPOSE: Gene therapy may show promise for stroke patients, but invasive techniques such as intraventricular or intracerebral injection of therapeutic genes may have limited applicability. The purpose of this study is to develop systemic gene therapy using macrophages infiltrating the infarct to deliver and express the gene. METHODS: After permanent middle cerebral artery occlusion in rats, an enhanced green fluorescent protein (EGFP) plasmid conjugate in liposomes was injected via the femoral vein. We also constructed a bicistronic plasmid vector for fibroblast growth factor-2 (FGF-2) as well as EGFP, administering it in other rats with middle cerebral artery occlusion. RESULTS: EGFP expression in normal brain was absent but was strong in macrophages accumulating along the infarct border. FGF-2 protein production was induced in macrophages along the infarct border after injection of bicistronic FGF-2 and EGFP plasmid vector; this stimulated proliferation of neural progenitors in the subventricular zone in the ischemic hemisphere compared with control plasmid vectors (61.7+/-5.2 versus 42.2+/-5.5 cells per mm2, n=4 each, P<0.01). CONCLUSIONS: Systemic gene transfer by liposome to macrophages infiltrating an infarct may prove useful for gene therapy in stroke.}, Author = {Tanaka, Shigeru and Kitagawa, Kazuo and Sugiura, Shiro and Matsuoka-Omura, Emi and Sasaki, Tsutomu and Yagita, Yoshiki and Hori, Masatsugu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1524-4628}, Journal = {Stroke}, Keywords = {Animals;Genes, erbB-1;Rats;Macrophages;Infarction, Middle Cerebral Artery;Cell Movement;Liposomes;Cerebral Infarction;Not relevant;Cell Proliferation;Male;Genetic Vectors;11 Glia;Green Fluorescent Proteins;Disease Models, Animal;Plasmids;Fibroblast Growth Factor 2;Rats, Wistar;Gene Therapy;Gene Transfer Techniques;Neurons;Stem Cells;Research Support, Non-U.S. Gov't}, Month = {8}, Nlm_Id = {0235266}, Number = {8}, Organization = {Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan.}, Pages = {1968-73}, Pii = {01.STR.0000133685.59556.a7}, Pubmed = {15192242}, Title = {Infiltrating macrophages as in vivo targets for intravenous gene delivery in cerebral infarction}, Uuid = {AFEB2555-3643-4BED-9880-DC0E68791B55}, Volume = {35}, Year = {2004}, url = {papers/Tanaka_Stroke2004a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.STR.0000133685.59556.a7}} @article{Tanaka:2004, Abstract = {BACKGROUND AND PURPOSE: Neurogenesis has been observed in the dentate gyrus of the adult hippocampus; however, the mechanisms involved in this process are still only partly understood. In this study, we visualized the proliferation, migration, and differentiation of neuronal progenitor cells in the dentate gyrus induced by ischemic stress using improved retroviral vector. METHODS: Improved retroviral vector expressing enhanced green fluorescent protein (EGFP) as a transgene was injected into the dentate gyrus of adult Mongolian gerbils. After 48 hours, transient global ischemia (TGI) was induced by bilateral common carotid artery occlusion for 5 minutes using aneurysm clips. The morphological and immunohistological features of newly-generated cells in the dentate gyrus were analyzed at various times thereafter. RESULTS: At 48 hours after viral injection, almost all EGFP-positive dividing cells were found in the subgranule layer (SGL). These cells proliferated and migrated to the granule cell layer (GCL), expressing the developing neuronal markers polysialic acid and doublecortin, and differentiated to neuronal nuclei-positive or calbindin-positive mature granule cells at 30 days after TGI or sham-operation. The number of GFP-positive cells in the GCL was significantly higher (P<0.05) in the ischemic animals at 30 days than in sham-operated gerbils. CONCLUSIONS: We saw neurogenesis in the adult dentate gyrus. Furthermore, we showed that ischemic stress promoted the proliferation and normal development of neurons at this site.}, Author = {Tanaka, Ryota and Yamashiro, Kazuo and Mochizuki, Hideki and Cho, Nei and Onodera, Masafumi and Mizuno, Yoshikuni and Urabe, Takao}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1524-4628}, Journal = {Stroke}, Keywords = {Genetic Vectors;Indicators and Reagents;Cell Differentiation;Luminescent Proteins;Animals;Dentate Gyrus;Stem Cells;Retroviridae;Cell Division;06 Adult neurogenesis injury induced;Gerbillinae;Male;Cell Movement;Support, Non-U.S. Gov't;Neurons;Ischemic Attack, Transient}, Month = {6}, Nlm_Id = {0235266}, Number = {6}, Organization = {Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Tokyo, Japan.}, Pages = {1454-9}, Pii = {01.STR.0000126480.40967.b3}, Pubmed = {15073392}, Title = {Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector}, Uuid = {E59FC3FD-200C-4F66-BEA8-4E01B0F28C23}, Volume = {35}, Year = {2004}, url = {papers/Tanaka_Stroke2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.STR.0000126480.40967.b3}} @article{Tanapat:1998, Abstract = {The granule cell population of the dentate gyrus is produced predominantly during the postnatal period in rats. Previous studies have shown that experimental increases in the levels of adrenal steroids suppress the proliferation of granule cell precursors during the first postnatal week, the time of maximal neurogenesis in the dentate gyrus. These findings raise the possibility that stressful experiences that elevate adrenal steroid levels may inhibit the production of granule neurons, and thus alter the development of the dentate gyrus. To test this possibility, we exposed naive rat pups to the odors of a known predator, adult male rats, and examined both plasma corticosterone levels and the number of 3H-thymidine labeled cells in the dentate gyrus. A single exposure of rat pups to adult male rat odor elevated corticosterone levels immediately and diminished the number of 3H-thymidine labeled cells in the granule cell layer by 24 h later. These results suggest that stressful experiences suppress the production of granule neurons in the developing dentate gyrus.}, Author = {Tanapat, P. and Galea, L. A. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Int J Dev Neurosci}, Keywords = {Animals, Newborn/*growth &development;Odors;Cell Division/physiology;Rats, Sprague-Dawley;Stress/blood/etiology/*pathology;Embryo/pathology;Rats;C;Aging/physiology;Animal;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Male;Dentate Gyrus/*embryology/*growth &development/pathology;Neurons/*pathology;Fetal Development/physiology;Stem Cells/*pathology}, Number = {3-4}, Organization = {Department of Psychology, Princeton University, NJ 08544, USA.}, Pages = {235-9.}, Pubmed = {9785120}, Title = {Stress inhibits the proliferation of granule cell precursors in the developing dentate gyrus}, Uuid = {C9E0E1A1-2EF7-4D41-9BF2-A15FADFFBDA4}, Volume = {16}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Retrieve&list_uids=9785120&dopt=Citation}} @article{Tanapat:1999, Abstract = {To determine whether a sex difference exists in the production of hippocampal cells during adulthood, we examined proliferating cells and their progeny in adult rats using the thymidine analog bromodeoxyuridine (BrdU) combined with immunohistochemistry for markers of neurons and glia. Additionally, to determine whether ovarian hormones affect cell proliferation, we examined the numbers of BrdU- labeled cells at different estrous cycle stages and after ovarian steroid manipulation. Stereological analyses of the numbers of BrdU- labeled cells revealed that females produced more cells than males in the dentate gyrus but not in the subventricular zone. The production of new hippocampal cells in females appears to be affected by ovarian hormone levels; ovariectomy diminished the number of BrdU-labeled cells, an effect reversed by estrogen replacement. A natural fluctuation in cell proliferation was also noted; females produced more cells during proestrus (when estrogen levels are highest) compared with estrus and diestrus. Many of these cells acquired neuronal characteristics, including the formation of dendrites and expression of Turned-On-After-Division 64 kDa, a marker of immature granule neurons, and the calcium-binding protein calbindin, a marker of mature granule neurons. However, examination of the numbers of pyknotic cells and the numbers of BrdU-labeled cells at longer survival times revealed that many new cells in the dentate gyrus eventually degenerate. Consistently the number of labeled cells in females is no longer higher than that observed in males by 2 weeks after the last BrdU injection. These findings suggest that estrogen-enhanced cell proliferation during proestrus results in more immature neurons in the hippocampal formation of females compared with males and present the possibility that these new cells exert an important influence on hippocampal function.}, Author = {Tanapat, P. and Hastings, N. B. and Reeves, A. J. and Gould, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Neurosci}, Keywords = {Rats;Estrus/*physiology;Microscopy, Confocal;C-9;Female;Animal;Rats, Sprague-Dawley;Nerve Tissue Proteins/analysis;Dentate Gyrus/*cytology;Male;Estradiol/*pharmacology/physiology;Neuroglia/*cytology/drug effects;Sex Characteristics;04 Adult neurogenesis factors;Ovariectomy;Support, U.S. Gov't, P.H.S.;Bromodeoxyuridine;Hippocampus/*cytology;Cell Division/drug effects;Neurons/*cytology/drug effects}, Number = {14}, Organization = {Department of Psychology, Princeton University, Princeton, New Jersey 08544, USA.}, Pages = {5792-801.}, Title = {Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat}, Uuid = {8428E986-0BF2-45C5-8C60-259AE0A994D2}, Volume = {19}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10407020%20http://www.jneurosci.org/cgi/content/full/19/14/5792%20http://www.jneurosci.org/cgi/content/abstract/19/14/5792}} @article{Tanigaki:2001, Abstract = {Notch1 has been shown to induce glia in the peripheral nervous system. However, it has not been known whether Notch can direct commitment to glia from multipotent progenitors of the central nervous system. Here we present evidence that activated Notch1 and Notch3 promotes the differentiation of astroglia from the rat adult hippocampus-derived multipotent progenitors (AHPs). Quantitative clonal analysis indicates that the action of Notch is likely to be instructive. Transient activation of Notch can direct commitment of AHPs irreversibly to astroglia. Astroglial induction by Notch signaling was shown to be independent of STAT3, which is a key regulatory transcriptional factor when ciliary neurotrophic factor (CNTF) induces astroglia. These data suggest that Notch provides a CNTF-independent instructive signal of astroglia differentiation in CNS multipotent progenitor cells. 0896-6273 Journal Article}, Author = {Tanigaki, K. and Nogaki, F. and Takahashi, J. and Tashiro, K. and Kurooka, H. and Honjo, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Neuron}, Keywords = {Astrocytes/*metabolism;Clone Cells/drug effects;Cell Differentiation/drug effects;Proto-Oncogene Proteins/*metabolism/pharmacology;Animals;Cells, Cultured;Membrane Proteins/*metabolism/pharmacology;Rats;10 Development;Ciliary Neurotrophic Factor/metabolism/pharmacology;Trans-Activators/metabolism;Signal Transduction/drug effects;Cell Lineage/drug effects;Neurons/cytology/drug effects/metabolism;DNA-Binding Proteins/metabolism;Support, Non-U.S. Gov't;Stem Cells/cytology/drug effects/*metabolism;Hippocampus/cytology/metabolism;Fibroblast Growth Factor 2/*metabolism/pharmacology;F}, Number = {1}, Organization = {Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida-Konoe Sakyo, 606-8501, Kyoto, Japan.}, Pages = {45-55}, Pubmed = {11182080}, Title = {Notch1 and Notch3 instructively restrict bFGF-responsive multipotent neural progenitor cells to an astroglial fate}, Uuid = {CAC346CF-76C9-43DF-ABE8-8C0353B8EEBC}, Volume = {29}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11182080}} @article{Taniguchi:2001, Abstract = {Reciprocal dendrodendritic synapses between mitral and granule cells in the accessory olfactory bulb have been implicated in a specialized form of olfactory learning in mice, in which a female forms a memory to the pheromonal signal of the male that mates with her. Relatively little is known, however, about the mechanism of synaptic transmission at the reciprocal synapses. We analyzed synaptic currents generated in accessory olfactory bulb mitral cells in slice preparations with the patch-clamp technique in nystatin-perforated whole-cell configuration. A brief (5-20-ms) depolarizing voltage step from -70 to 0 mV applied to a single mitral cell evoked GABA(A) receptor-mediated inhibitory postsynaptic currents. The inhibitory postsynaptic currents persisted in the presence of tetrodotoxin, indicating that the inhibitory postsynaptic current in mitral cells can be elicited through purely dendritic interactions. The inhibitory postsynaptic currents were greatly enhanced by washout of extracellular Mg(2+). In Mg(2+)-free solution, the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2- amino-5-phosphonovaleric acid greatly reduced the inhibitory postsynaptic currents, whereas the non-NMDA receptor antagonist 6-cyano- 7-nitroquinoxaline-2,3-(1H,4H)-dione (CNQX) slightly reduced them.These data demonstrate that NMDA receptors play an important role in the generation of dendrodendritic inhibition in mitral cells of the mouse accessory olfactory bulb.}, Author = {Taniguchi, M. and Kaba, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Neuroscience}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {3}, Pages = {365-70.}, Title = {Properties of reciprocal synapses in the mouse accessory olfactory bulb}, Uuid = {7AADD09A-71E4-43F5-9EC9-7F0C71DD0A0A}, Volume = {108}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11738251}} @article{Tansey:1998, Abstract = {The present study addresses a controversy over the abilities of astrocytes to perform phagocytosis. Primary glial-cell cultures were prepared from the brains of neonatal rats and were incubated with fluorescently-labeled dextran beads (molecular weights approximately 10 and approximately 40 kDa). Astrocytes and oligodendrocytes were double-labeled by immunofluorescence staining of cell-specific markers, and microglia by lectin histochemistry. Cells were permitted to take up beads for 1 h, fixed, and incubated with primary antibodies, followed by fluorescent secondary antibodies or fluorescently-labeled lectin. Macrophages and astrocytes internalized beads of both sizes. In astrocyte processes the beads appeared to line up along glial filaments. The results, which provide direct evidence for uptake of beads by astrocytes in vitro and against equally rapid, if any, uptake by oligodendrocytes, bear upon issues of acid/base balance and glial cell development and are relevant to neuropathological observations in human disease.}, Author = {Tansey, F. A. and Cammer, W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Research Support, Non-U.S. Gov't;Fluorescent Antibody Technique, Indirect;Astrocytes;Animals;Macrophages;Rats;Dextrans;Cells, Cultured;Brain;Microglia;Oligodendroglia;Rats, Sprague-Dawley;11 Glia;Microspheres;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Neuroglia;Lectins;Glial Fibrillary Acidic Protein}, Medline = {98316905}, Month = {6}, Nlm_Id = {7600130}, Number = {3}, Organization = {Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.}, Pages = {159-62}, Pii = {S0304394098003735}, Pubmed = {9654333}, Title = {Differential uptake of dextran beads by astrocytes, macrophages and oligodendrocytes in mixed glial-cell cultures from brains of neonatal rats}, Uuid = {890553FC-08E5-4044-9568-ADEDDEF0B207}, Volume = {248}, Year = {1998}} @article{Tao:2004, Abstract = {Genetic modification of hematopoietic stem and progenitor cells has the potential to treat diseases affecting blood cells. Oncoretroviral vectors have been used for gene therapy; however, clinical success has been limited in part by low gene transfer efficiencies. We found that the presence of stromal-derived factor 1 (SDF-1alpha)/CXCL12 during retroviral transduction significantly enhanced, in a dose-dependent fashion, gene transfer into immature subsets of high proliferative human and murine hematopoietic progenitor cells. Murine mononuclear bone marrow cells and purified c-Kit(+)Lin(-) bone marrow cells were prestimulated and transduced with the bicistronic retroviral vector MIEG3 on Retronectin-coated surfaces in the presence and absence of SDF-1. SDF-1 enhanced gene transduction of murine bone marrow and c-Kit(+)Lin(-) cells by 35 and 29\%, respectively. Moreover, SDF-1 enhanced transduction of progenitors in these populations by 121 and 107\%, respectively. SDF-1 also enhanced transduction of human immature subsets of high proliferative progenitors present in either nonadherent mononuclear or CD34(+) umbilical cord blood cells. Transduction of hematopoietic progenitors was further increased by preloading Retronectin-coated plates with retrovirus using low-speed centrifugation followed by increasing cell-virus interactions through brief centrifugation during the transduction procedure. These results may be of clinical relevance.}, Author = {Tao, W. and Hangoc, G. and Cooper, S. and Broxmeyer, H. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Genetic Vectors;Transduction, Genetic;Research Support, Non-U.S. Gov't;Luminescent Proteins;Hematopoietic Stem Cells;Research Support, U.S. Gov't, P.H.S.;Mice, Inbred C57BL;Retroviridae;Gene Expression;11 Glia;Gene Therapy;Chemokines, CXC;Mice;Animals;Green Fluorescent Proteins;Humans;Hematologic Diseases}, Month = {1}, Nlm_Id = {9421525}, Number = {1}, Organization = {Department of Microbiology and Immunology, The Walther Oncology Center, Indiana University School of Medicine, Indianapolis, IN 46202-5181, USA.}, Pages = {61-9}, Pii = {3302127}, Pubmed = {14681698}, Title = {SDF-1alpha/CXCL12 enhances retroviral-mediated gene transfer into immature subsets of human and murine hematopoietic progenitor cells}, Uuid = {53107025-7E51-473F-BEB8-E2A29231D1AF}, Volume = {11}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj.gt.3302127}} @article{Tao:1999, Abstract = {Immature motoneurons are highly susceptible to degeneration following axon injury. The response of perineuronal glia to axon injury may significantly influence neuronal survival and axon regeneration. We have examined the central reactions to neonatal facial nerve transection with emphasis on the expression of complement component C3 (C3) and the multifunctional apolipoprotein J (ApoJ). Axotomy was performed on one-day-old rats. Animals were perfused from eight hours to two weeks after the lesion. The astroglial marker, glial fibrillary acidic protein (GFAP) was increased from one day and the microglial marker OX-42 from two days after injury. ApoJ immunoreactivity was increased in axotomized neuronal perikarya and astroglial cells from one day postaxotomy, but no C3 immunoreactive profiles were found at any postoperative survival time. Cell proliferation as judged by bromodeoxyuridine labeling and immunoreactivity for the cyclin Ki-67 antigen (antibody MIB5) occurred only at two days after injury. Double immunostaining revealed that the vast majority of proliferating cells were microglia, although occasional cells double labeled astrocytes were found as well. Our results indicate that the non-neuronal response in neonatal animals differ from that of adult ones as follows: 1) microglia transform rapidly into phagocytes in parallel with the degeneration of axotomized neurons, 2) despite the presence of neuronal degeneration, no expression of C3 was found, and the upregulation of the expression of the complement C3 receptor (CR3) is delayed, 3) ApoJ is strongly upregulated in perineuronal astrocytes as well as in the axotomized motoneurons. The marked upregulation of ApoJ in both instances suggests a general role of this protein in the neuronal response to axotomy.}, Author = {Tao, R. and Aldskogius, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Glycoproteins;Nerve Degeneration;Fluorescent Antibody Technique, Indirect;Astrocytes;Gene Expression Regulation;Aging;Rats;Animals;Microglia;Oligodendroglia;Rats, Sprague-Dawley;Nerve Regeneration;Animals, Newborn;Neuroglia;Molecular Chaperones;Axotomy;Neurons;Cell Division;24 Pubmed search results 2008;Immunohistochemistry;Complement 3;Facial Nerve;Research Support, Non-U.S. Gov't}, Medline = {20261710}, Month = {7}, Nlm_Id = {0364620}, Number = {7}, Organization = {Department of Neuroscience, Division of Neuroanatomy, Biomedical Center, P.O. Box 587, SE-751 23 Uppsala, Sweden.}, Pages = {559-70}, Pubmed = {10800205}, Title = {Glial cell responses, complement and apolipoprotein J expression following axon injury in the neonatal rat}, Uuid = {62BA6F7E-C329-44ED-88EB-5DDBACE6610E}, Volume = {28}, Year = {1999}} @article{Tao:2002, Abstract = {Transcription of the brain-derived neurotrophic factor (BDNF) gene is regulated in a calcium- and neuron-selective manner; however, the mechanisms that underlie this selectivity are not known. We have characterized a new calcium-response element, CaRE1, that is required for activity-dependent transcription of BDNF exon III and have cloned a transcription factor, CaRF, that activates transcription from BDNF promoter III in a CaRE1-dependent manner. The transcriptional activity of CaRF is regulated in a calcium- and neuron-selective manner, suggesting that CaRF may confer selectivity upon the activity-dependent induction of BDNF exon III expression.}, Author = {Tao, Xu and West, Anne E. and Chen, Wen G. and Corfas, Gabriel and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Two-Hybrid System Techniques;Transcription Factors;Tissue Distribution;Rats, Long-Evans;Gene Expression Regulation;Animals;Rats;Cells, Cultured;Humans;Brain-Derived Neurotrophic Factor;research support, u.s. gov't, p.h.s. ;Exons;Brain;Calcium;Microscopy, Fluorescence;Cyclic AMP;In Situ Hybridization;research support, non-u.s. gov't ;21 Neurophysiology;Neurons;Regulatory Sequences, Nucleic Acid;Response Elements;Nuclear Proteins;24 Pubmed search results 2008;Amino Acid Sequence;Genes, Reporter;Molecular Sequence Data;1-Methyl-3-isobutylxanthine;Phosphodiesterase Inhibitors}, Month = {1}, Nlm_Id = {8809320}, Number = {3}, Organization = {Division of Neuroscience, Children's Hospital, Boston, MA 02115, USA.}, Pages = {383-95}, Pii = {S089662730100561X}, Pubmed = {11832226}, Title = {A calcium-responsive transcription factor, CaRF, that regulates neuronal activity-dependent expression of BDNF}, Uuid = {3C69B97F-B331-4140-987F-D54C6A34F67B}, Volume = {33}, Year = {2002}} @article{Tarantal:2001, Abstract = {Many life-threatening conditions that can be diagnosed early in gestation may be treatable in utero using gene therapy. In order to determine in utero gene transfer efficiency and safety, studies were conducted with fetal rhesus monkeys as a model for the human. Included in these studies were Moloney murine leukemia virus (MLV)-based amphotropic retrovirus, vesicular stomatitis virus-G (VSV-G) pseudotyped MLV, and a VSV-G pseudotyped HIV-1-based vector, all expressing the enhanced green fluorescent protein (EGFP) as a reporter gene and driven by a cytomegalovirus-immediate early promoter (N = 16). Rhesus monkey fetuses were administered viral vector supernatant preparations by the intraperitoneal (ip) (N = 14) or intrahepatic (ih) (N = 2) routes via ultrasound guidance at 55 +/- 5 days gestation (late first trimester; term 165 +/- 10 days). Fetuses were monitored sonographically, specimens were collected prenatally and postnatally, and tissue harvests were performed at birth or 3 or 6 months postnatal age (3-10 months post-gene transfer). PCR analyses demonstrated that transduced cells were present at approximately 1.2\%in peripheral blood mononuclear cells from fetuses administered amphotropic MLV, <0.5\%in fetuses receiving MLV/VSV-G, and approximately 4.2\%for the lentiviral vector, which decreased to 2\%at birth. Hematopoietic progenitors showed that overall (mean of all time points assessed), approximately 25\%of the collected colonies were positive for the EGFP transgene with the lentiviral vector, which was significantly greater than results achieved with the MLV-based vector systems (4-9\%; P }, Pages = {198-214}, Pii = {S0165-0173(06)00104-4}, Pubmed = {17020783}, Title = {BrdU immunohistochemistry for studying adult neurogenesis: paradigms, pitfalls, limitations, and validation}, Uuid = {C68C4E8B-D702-474F-A84A-B0CF90F722EB}, Volume = {53}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainresrev.2006.08.002}} @article{Taupin:2000, Abstract = {We have purified and characterized a factor, from the conditioned medium of neural stem cell cultures, which is required for fibroblast growth factor 2's (FGF-2) mitogenic activity on neural stem cells. This autocrine/paracrine cofactor is a glycosylated form of cystatin C (CCg), whose N-glycosylation is required for its activity. We further demonstrated that, both in vitro and in vivo, neural stem cells undergoing cell division are immunopositive for cystatin C. Finally, we showed in vivo functional activity of CCg by demonstrating that the combined delivery of FGF-2 and CCg to the adult dentate gyrus stimulated neurogenesis. We propose that the process of neurogenesis is controlled by the cooperation between trophic factors and autocrine/paracrine cofactors, of which CCg is a prototype. 0896-6273 Journal Article}, Author = {Taupin, P. and Ray, J. and Fischer, W. H. and Suhr, S. T. and Hakansson, K. and Grubb, A. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Neuron}, Keywords = {Hippocampus/cytology/drug effects/metabolism;10 Development;Animals;Stem Cell Transplantation;Cells, Cultured;Rats;Autocrine Communication/drug effects;Paracrine Communication/drug effects;Cystatins/*chemistry/genetics/*metabolism/pharmacology;Glycosylation;Support, Non-U.S. Gov't;Fibroblast Growth Factor 2/genetics/*metabolism/pharmacology;Neurons/cytology/drug effects/*metabolism;Dentate Gyrus/cytology/drug effects;Sequence Analysis, Protein;Stem Cells/cytology/drug effects/*metabolism;Support, U.S. Gov't, P.H.S.;Protein Processing, Post-Translational;Molecular Weight;Molecular Sequence Data;F;Culture Media, Conditioned/chemistry;Cell Division/drug effects}, Number = {2}, Organization = {Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA.}, Pages = {385-97}, Pubmed = {11144350}, Title = {FGF-2-responsive neural stem cell proliferation requires CCg, a novel autocrine/paracrine cofactor}, Uuid = {A93AFF42-8CEF-42C4-9352-B08B9C84F46B}, Volume = {28}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11144350}} @article{Tavazoie:2005, Abstract = {Mutations in the TSC1 or TSC2 tumor suppressor genes lead to tuberous sclerosis complex (TSC), a dominant hamartomatous disorder that often presents with mental retardation, epilepsy and autism. The etiology of these neurological symptoms is unclear and the function of the TSC pathway in neurons is unknown. We found that in post-mitotic, hippocampal pyramidal neurons of mice and rats, loss of Tsc1 or Tsc2 triggered enlargement of somas and dendritic spines and altered the properties of glutamatergic synapses. Furthermore, loss of a single copy of the Tsc1 gene was sufficient to perturb dendritic spine structure. Morphological changes required regulation of the actin-depolymerization factor cofilin at a conserved LIM-kinase phosphorylation site, the phosphorylation of which was increased by loss of Tsc2. Thus, the TSC pathway regulates growth and synapse function in neurons, and perturbations of neuronal structure and function are likely to contribute to the pathogenesis of the neurological symptoms of TSC.}, Author = {Tavazoie, Sohail F. and Alvarez, Veronica A. and Ridenour, Dennis A. and Kwiatkowski, David J. and Sabatini, Bernardo L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Cell Differentiation;research support, n.i.h., extramural ;Animals;Humans;Gene Expression Regulation, Developmental;Rats;Phosphorylation;Tuberous Sclerosis;Cofilin 1;research support, u.s. gov't, non-p.h.s. ;Dendritic Spines;Brain;Rats, Sprague-Dawley;Hippocampus;Pyramidal Cells;Mice, Transgenic;research support, non-u.s. gov't ;Cell Line;Mice, Knockout;21 Neurophysiology;Cell Shape;Neurons;Mice;Tumor Suppressor Proteins;24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {9809671}, Number = {12}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, Massachusetts 02115, USA.}, Pages = {1727-34}, Pii = {nn1566}, Pubmed = {16286931}, Title = {Regulation of neuronal morphology and function by the tumor suppressors Tsc1 and Tsc2}, Uuid = {CEEDF056-1F1F-4622-B0A0-0FB3DE2433F8}, Volume = {8}, Year = {2005}, url = {papers/Tavazoie_NatNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1566}} @article{Taylor:2002, Abstract = {A key feature of myogenesis is the fusion of myoblasts to form multinucleate myotubes. Recent work in Drosophila has uncovered a collection of genes that operate at different stages of this process. Some interactions between them have been described that begin to define links from outside the cell via the plasma membrane to the cytoskeleton. Future studies will establish the extent to which the molecular mechanisms of myoblast fusion are conserved between Drosophila and other animals, as found in other aspects of myogenesis.}, Author = {Taylor, Michael V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Cell Membrane;Cell Differentiation;Cell Fusion;Gene Expression Regulation, Developmental;Muscles;Embryo, Nonmammalian;Sodium Channels;08 Aberrant cell cycle;Drosophila Proteins;Insect Proteins;Drosophila;review, tutorial;Mesoderm;Animals;Cytoplasm;review}, Medline = {21906656}, Month = {3}, Nlm_Id = {9107782}, Number = {6}, Organization = {Cardiff School of Biosciences, Cardiff University, UK. TaylorMV\@cf.ac.uk}, Pages = {R224-8}, Pii = {S0960982202007571}, Pubmed = {11909553}, Title = {Muscle differentiation: how two cells become one}, Uuid = {6D9AB901-B180-413D-8C17-8B1E5F449A96}, Volume = {12}, Year = {2002}, url = {papers/Taylor_CurrBiol2002.pdf}} @article{Taylor:1999, Abstract = {The role of glycoprotein membrane-spanning domains in the process of membrane fusion is poorly understood. It has been demonstrated that replacing all or part of the membrane-spanning domain of a viral fusion protein with sequences that encode signals for glycosylphosphatidylinositol linkage attachment abrogates membrane fusion activity. It has been suggested, however, that the actual amino acid sequence of the membrane-spanning domain is not critical for the activity of viral fusion proteins. We have examined the function of Moloney murine leukemia virus envelope proteins with substitutions in the membrane-spanning domain. Envelope proteins bearing substitutions for proline 617 are processed and incorporated into virus particles normally and bind to the viral receptor. However, they possess greatly reduced or undetectable capacities for the promotion of membrane fusion and infectious virus particle formation. Our results imply a direct role for the residues in the membrane-spanning domain of the murine leukemia virus envelope protein in membrane fusion and its regulation. They also support the thesis that membrane-spanning domains possess a sequence-dependent function in other protein-mediated membrane fusion events.}, Author = {Taylor, G. M. and Sanders, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1059-1524}, Journal = {Mol Biol Cell}, Keywords = {Proline;Glycoproteins;Conserved Sequence;Animals;Gene Products, env;Mutation;Virus Assembly;Cell Fusion;Amino Acid Substitution;15 Retrovirus mechanism;Giant Cells;08 Aberrant cell cycle;Cell Line;Support, Non-U.S. Gov't;Moloney murine leukemia virus;Membrane Fusion;Support, U.S. Gov't, P.H.S.;Receptors, Virus;Mice;Protein Processing, Post-Translational;Amino Acid Sequence;Molecular Sequence Data;Membrane Proteins}, Medline = {99402792}, Month = {9}, Nlm_Id = {9201390}, Number = {9}, Organization = {Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.}, Pages = {2803-15}, Pubmed = {10473628}, Title = {The role of the membrane-spanning domain sequence in glycoprotein-mediated membrane fusion}, Uuid = {C07717A5-EC27-4151-BBF3-F7A6F137E119}, Volume = {10}, Year = {1999}, url = {papers/Taylor_MolBiolCell1999.pdf}} @article{Taylor:2004, Abstract = {The programmed cell death (PCD) of neurons is generally thought to be cell autonomous and not to require a death signal from other cells. A recent study by Mar{\'\i}n-Teva et al., in this issue of Neuron, brings this theory into question and suggests that neighboring microglia actively participate in the PCD of Purkinje cells in the cerebellum.}, Author = {Taylor, Anna R. and Oppenheim, Ronald W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Membrane Lipids;Purkinje Cells;Alpha;Cell Communication;Apoptosis;Signal Transduction;Not relevant;11 Glia;Microglia;comment;Animals;Caspases;news}, Month = {2}, Nlm_Id = {8809320}, Number = {4}, Organization = {Department of Neurobiology and Anatomy, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157, USA.}, Pages = {491-3}, Pii = {S0896627304000790}, Pubmed = {14980198}, Title = {The kiss of death}, Uuid = {02F2AA1E-4C90-4FEE-A8E4-477F13C0BFF9}, Volume = {41}, Year = {2004}} @article{Tchantchou:2007, Abstract = {Standardized Ginkgo biloba extract EGb 761 exhibits beneficial effects to patients with Alzheimer's disease (AD). It was previously demonstrated that EGb 761 inhibits amyloid beta (Abeta) oligomerization in vitro, protects neuronal cells against Abeta toxicity, and improves cognitive defects in a mouse model of AD (Tg 2576). In this study, the neurogenic potential of EGb 761 and its effect on cAMP response element binding protein (CREB) were examined in a double transgenic mouse model (TgAPP/PS1). EGb 761 significantly increases cell proliferation in the hippocampus of both young (6 months) and old (22 months) TgAPP/PS1 mice, and the total number of neuronal precursor cells in vitro in a dose-dependent manner. Furthermore, Abeta oligomers inhibit phosphorylation of CREB and cell proliferation in the hippocampus of TgAPP/PS1 mice. Administration of EGb 761 reduces Abeta oligomers and restores CREB phosphorylation in the hippocampus of these mice. The present findings suggest that 1) enhanced neurogenesis by EGb 761 may be mediated by activation of CREB, 2) stimulation of neurogenesis by EGb 761 may contribute to its beneficial effects in AD patients and improved cognitive functions in the mouse model of AD, and 3) EGb 761 has therapeutic potential for the prevention and improved treatment of AD.--Tchantchou, F., Xu, Y., Wu, Y., Christen, Y., Luo, Y. EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease.}, Author = {Tchantchou, and Xu, and Wu, and Christen, and Luo,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1530-6860}, Journal = {FASEB J}, Keywords = {04 Adult neurogenesis factors;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8804484}, Organization = {*Department of Pharmaceutical Sciences, School of Pharmacy,Center for Integrative Medicine, School of Medicine, University of Maryland, Baltimore, Maryland, USA; andIpsen, Paris, France.}, Pii = {fj.06-7649com}, Pubmed = {17356006}, Title = {EGb 761 enhances adult hippocampal neurogenesis and phosphorylation of CREB in transgenic mouse model of Alzheimer's disease}, Uuid = {2A129A89-A49E-4F0F-BD2F-5863B80CE0CB}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1096/fj.06-7649com}} @article{Teich:1973, Author = {Teich, N. and Lowy, D. R. and Hartley, J. W. and Rowe, W. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {15 ERVs retroelements;Radiation Effects;Immune Sera;Animals;Idoxuridine;DNA;Ultraviolet Rays;Thymidine;15 Retrovirus mechanism;Time Factors;Leukemia Virus, Murine;Cell Line;Cytarabine;Light;Mice;Floxuridine;24 Pubmed search results 2008;Bromodeoxyuridine;Virus Replication;Clone Cells;Plaque Assay;Mice, Inbred AKR}, Medline = {73086525}, Month = {1}, Nlm_Id = {0110674}, Number = {1}, Pages = {163-73}, Pii = {0042-6822(73)90376-0}, Pubmed = {4346294}, Title = {Studies of the mechanism of induction of infectious murine leukemia virus from AKR mouse embryo cell lines by 5-iododeoxyuridine and 5-bromodeoxyuridine}, Uuid = {833A299F-4326-11DB-A5D2-000D9346EC2A}, Volume = {51}, Year = {1973}} @article{Tekin:2002, Abstract = {Frontal-subcortical circuits form the principal network, which mediate motor activity and behavior in humans. Five parallel frontal-subcortical circuits link the specific areas of the frontal cortex to the striatum, basal ganglia and thalamus. These frontal-subcortical circuits originate from the supplementary motor area, frontal eye field, dorsolateral prefrontal region, lateral orbitofrontal region and anterior cingulate portion of the frontal cortex. The open afferent and efferent connections to the frontal-subcortical circuits mediate coordination between functionally similar areas of the brain. Specific chemoarchitecture and multiple neurotransmitter interactions modulate the functional activity of each circuit. Dorsolateral prefrontal circuit lesions cause executive dysfunction, orbitofrontal circuit lesions lead to personality changes characterized by disinhibition and anterior cingulate circuit lesions present with apathy. The neurobiological correlates of neuropsychiatric disorders including depression, obsessive-compulsive disorder, schizophrenia and substance abuse, imply involvement of frontal-subcortical circuits.}, Author = {Tekin, Sibel and Cummings, Jeffrey L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0022-3999}, Journal = {J Psychosom Res}, Keywords = {24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Neural Pathways;Research Support, U.S. Gov't, P.H.S.;Neurochemistry;review, tutorial;Nerve Net;Humans;Brain;Cerebral Cortex;review;Frontal Lobe}, Medline = {22160012}, Month = {8}, Nlm_Id = {0376333}, Number = {2}, Organization = {Department of Neurology, UCLA School of Medicine, 90095, USA.}, Pages = {647-54}, Pii = {S0022399902004282}, Pubmed = {12169339}, Title = {Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update}, Uuid = {E18ABEE1-8592-4109-8B62-81C5AD58BC8A}, Volume = {53}, Year = {2002}} @article{Telfeian:1998, Abstract = {PURPOSE: Epileptiform discharges that resemble interictal spikes can be generated by slices of neocortex treated with antagonists of gamma-aminobutyric acid A (GABA(A)) receptors. These discharges can propagate horizontally for long distances. We tested the hypothesis that propagation occurs through preferred horizontal pathways that lie in a particular cortical layer. METHODS: Slices were prepared from the primary somatosensory cortex of rats, maintained in vitro, and bathed with the GABA(A) receptor antagonist picrotoxin. Electrical stimuli were used to evoke single all-or-none paroxysmal field potentials (PFP) that were recorded with pairs or arrays of field potential electrodes. RESULTS: To test which laminae are necessary for propagation, vertical cuts were made to force the PFP to spread horizontally through particular layers. If slices were bathed in a high dose of picrotoxin (35 microM), a bridge of cortex 350 microm thick placed at any lamina was sufficient to support PFP propagation. However, in low picrotoxin doses (2.5 microM), similarly sized bridges had to include tissue from layers 4/5 or 5/6 to support propagation. When slices were cut horizontally (i.e., parallel to the pia) in strips. either upper-, middle-, or lower-layer strips were sufficient to support PFP propagation if the picrotoxin concentration was high; however, in low picrotoxin doses, only horizontal strips that included layer 5 could support propagation. Finally, in intact picrotoxin-treated slices, focal applications of GABA were systematically applied to different laminae as the PFP propagated past; GABA was most effective at blocking or delaying propagation when it was applied to layer 5b. CONCLUSIONS: We conclude that epileptiform propagation can occur through a variety of horizontal pathways when cortical inhibition is strongly impaired. However, when inhibition is reduced only moderately, axonal pathways in layer 5 are critical for seizure spread.}, Author = {Telfeian, A. E. and Connors, B. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Epilepsy;Picrotoxin;Electroencephalography;Rats, Sprague-Dawley;Electric Stimulation;21 Neurophysiology;21 Epilepsy;Rats;Research Support, U.S. Gov't, P.H.S.;Neural Pathways;Dose-Response Relationship, Drug;Neocortex;Somatosensory Cortex;Animals;24 Pubmed search results 2008;GABA Antagonists;Membrane Potentials}, Medline = {98333972}, Month = {7}, Nlm_Id = {2983306R}, Number = {7}, Organization = {Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.}, Pages = {700-8}, Pubmed = {9670897}, Title = {Layer-specific pathways for the horizontal propagation of epileptiform discharges in neocortex}, Uuid = {08D1904A-F7DB-44C6-9DFC-2D2F2C65F20A}, Volume = {39}, Year = {1998}} @article{Telfeian:1999, Abstract = {PURPOSE: The neocortex can generate various forms of epileptiform activity, including one that depends on N-methyl-D-aspartate (NMDA)-type glutamate receptors (NMDARs), and another dependent on non-NMDA-type (AMPA) glutamate receptors (AMPARs). Previous work in vitro suggests that both forms of activity are initiated by neurons of layer 5, but the spatial patterns of horizontal propagation have been studied only for the AMPAR form. We have tested the hypothesis that both types of epileptiform activity spread via common pathways in one cortical layer, suggesting that lamina-specific intervention might selectively interrupt both. METHODS: Slices of rat somatosensory cortex were maintained in vitro and treated with the gamma-aminobutyric acid type A (GABA(A))-receptor antagonist picrotoxin. Single all-or-none epileptiform discharges were evoked with an electrical stimulus, and extracellular microelectrodes were used to track the vertical and lateral spread of the discharges. RESULTS: In both high and low concentrations of picrotoxin, the non-NMDAR antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) completely blocked propagation, whereas the NMDAR antagonist D-2-amino-5-phosphonovaleric acid (DAPV) only shortened the duration of discharges. When extracellular [Mg2+] was reduced in the presence of picrotoxin and CNQX, NMDAR-dependent epileptiform discharges could be initiated. NMDAR-dependent discharges spread at about one fifth the conduction velocity of AMPAR-dependent events. Analysis of spatiotemporal field-potential patterns suggested that both NMDAR- and AMPAR-mediated propagation involved early activity in layers 5 and 6, followed by larger-amplitude activity in upper cortical layers along the path of propagation. CONCLUSIONS: Our results imply that a common pathway mediates the propagation of these two forms of epileptiform activity, and suggests that lamina-specific surgical intervention might maximize anticonvulsant effect while minimally disrupting cortical function.}, Author = {Telfeian, A. E. and Connors, B. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Dose-Response Relationship, Drug;Animals;Evoked Potentials;Rats;Neural Pathways;21 Epilepsy;Neocortex;Epilepsy;Rats, Sprague-Dawley;2-Amino-5-phosphonovalerate;Receptors, AMPA;Magnesium;21 Neurophysiology;Picrotoxin;Somatosensory Cortex;6-Cyano-7-nitroquinoxaline-2,3-dione;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate}, Medline = {20029305}, Month = {11}, Nlm_Id = {2983306R}, Number = {11}, Organization = {Department of Neuroscience, Brown University, Providence, Rhode Island 02912, USA.}, Pages = {1499-506}, Pubmed = {10565575}, Title = {Epileptiform propagation patterns mediated by NMDA and non-NMDA receptors in rat neocortex}, Uuid = {58725955-9EB5-44A8-BE62-85B59FD4E913}, Volume = {40}, Year = {1999}} @article{Temple:1999, Abstract = {Over the past year, evidence has accrued that adult CNS stem cells are a widespread progenitor cell type. These cells may normally replace neurons and/or glia in the adult brain and spinal cord. Advances have been made in understanding the signals that regulate stem cell proliferation and differentiation. A deeper understanding of the structure of germinal zones has helped us move towards identifying stem cells in vivo. Recent studies suggest that the fate of stem cell progeny in vivo may be linked to the complexity of the animal's environment.}, Author = {Temple, S. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Curr Opin Neurobiol}, Keywords = {01 Adult neurogenesis general;02 Adult neurogenesis migration;Stem Cells/*cytology/*drug effects;Rats;03 Adult neurogenesis progenitor source;Animal;Fibroblast Growth Factor, Basic/pharmacology;Support, U.S. Gov't, P.H.S.;Cell Differentiation/drug effects;Epidermal Growth Factor/pharmacology;Central Nervous System/*cytology;Mice;A, BB pdf;Age Factors}, Number = {1}, Organization = {Department of Pharmacology and Neuroscience A-60 The Albany Medical College Albany New York 12208 USA. TempleS\@mail.amc.edu}, Pages = {135-41.}, Title = {Stem cells in the adult mammalian central nervous system}, Uuid = {F3D117FD-6F19-42D4-BF1E-6B7E5C23FDBB}, Volume = {9}, Year = {1999}, url = {papers/Temple_CurrOpinNeurobiol1999.pdf}} @article{Temple:2001, Author = {Temple, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:11:59 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {Blastocyst/cytology;Cell Lineage;02 Adult neurogenesis migration;Cell Differentiation/*physiology;Neurons/cytology;Brain/cytology/*embryology;03 Adult neurogenesis progenitor source;Human;Phenotype;Chick Embryo;BB both;Animal;Neuronal Plasticity/*physiology;Stem Cells/*cytology/*transplantation;Mice;Fetal Tissue Transplantation;Transplantation Chimera}, Number = {7}, Organization = {Center for Neuropharmacology and Neuroscience, Albany Medical College, 43 New Scotland Avenue, Albany, New York 12208, USA. temples\@mail.amc.edu}, Pages = {513-20.}, Title = {Stem cell plasticity--building the brain of our dreams}, Uuid = {75E82E95-3AB9-4DB7-B9BC-8A377BDA025E}, Volume = {2}, Year = {2001}, url = {papers/Temple_NatRevNeurosci2001.pdf}} @article{Temple:2001a, Abstract = {The discovery of stem cells that can generate neural tissue has raised new possibilities for repairing the nervous system. A rush of papers proclaiming adult stem cell plasticity has fostered the notion that there is essentially one stem cell type that, with the right impetus, can create whatever progeny our heart, liver or other vital organ desires. But studies aimed at understanding the role of stem cells during development have led to a different view - that stem cells are restricted regionally and temporally, and thus not all stem cells are equivalent. Can these views be reconciled? 0028-0836 Journal Article Review Review, Tutorial}, Author = {Temple, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Forecasting;Cell Differentiation;Human;Animals;Stem Cells/cytology/*physiology;Humans;10 Development;review, tutorial;Nervous System;review;Nervous System Diseases;Nervous System/*cytology/growth &development;Nervous System Diseases/therapy;Embryo/cytology;Embryo;Cell Lineage;22 Stem cells;Stem Cells;F}, Medline = {21548546}, Month = {11}, Nlm_Id = {0410462}, Number = {6859}, Organization = {Center for Neuropharmacology and Neurosciences, Albany Medical College, Albany, New York 12208, USA. temples\@mail.amc.edu}, Pages = {112-7}, Pii = {35102174}, Pubmed = {11689956}, Title = {The development of neural stem cells}, Uuid = {06502141-75BF-425A-9844-9CC25B7B857E}, Volume = {414}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35102174}, Bdsk-Url-2 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11689956}} @article{Terada:2002, Abstract = {Recent studies have demonstrated that transplanted bone marrow cells can turn into unexpected lineages including myocytes, hepatocytes, neurons and many others. A potential problem, however, is that reports discussing such 'transdifferentiation'in vivo tend to conclude donor origin of transdifferentiated cells on the basis of the existence of donor-specific genes such as Y-chromosome markers. Here we demonstrate that mouse bone marrow cells can fuse spontaneously with embryonic stem cells in culture in vitro that contains interleukin-3. Moreover, spontaneously fused bone marrow cells can subsequently adopt the phenotype of the recipient cells, which, without detailed genetic analysis, might be interpreted as 'dedifferentiation'or transdifferentiation. 0028-0836 Journal Article}, Author = {Terada, N. and Hamazaki, T. and Oka, M. and Hoki, M. and Mastalerz, D. M. and Nakano, Y. and Meyer, E. M. and Morel, L. and Petersen, B. E. and Scott, E. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {Nature}, Keywords = {Animals;Cells, Cultured;*Cell Differentiation;Phenotype;Antigens, Differentiation;Female;EE pdf;Mice, Transgenic;Interleukin-3/pharmacology;Embryo/cytology;Stem Cells/*cytology;Male;Reverse Transcriptase Polymerase Chain Reaction;*Cell Fusion;Karyotyping;Bone Marrow Cells/*cytology;Ploidies;Support, U.S. Gov't, P.H.S.;Mice;Luminescent Proteins/genetics;Genetic Markers}, Number = {6880}, Organization = {Department of Pathology, University of Florida College of Medicine, Gainesville, Florida 32610, USA. terada\@pathology.ufl.edu}, Pages = {542-5}, Title = {Bone marrow cells adopt the phenotype of other cells by spontaneous cell fusion}, Uuid = {6D02513A-CCCF-11D9-8C77-000D9346EC2A}, Volume = {416}, Year = {2002}, url = {papers/Terada_Nature2002.pdf}} @article{Terai:2003, Abstract = {The plasticity of bone marrow cells (BMCs) remains controversial. The present study found that persistent injury induces efficient trans-differentiation of BMCs into functional hepatocytes. Mice with liver cirrhosis induced by carbon tetrachloride were injected with 1 x 10(5) non-treated green fluorescent protein (GFP)-positive BMCs via the tail vein. In these mice, transplanted GFP-positive BMCs efficiently migrated into the peri-portal area of liver lobules after one day, repopulating 25\%of the recipient liver by 4 weeks. In contrast, no GFP-positive BMCs were detected following transplantation into control mice with undamaged livers. BMCs trans-differentiated into functional mature hepatocytes via immature hepatoblasts. Serum albumin levels were significantly elevated to compensate for chronic liver failure in BMC transplantation. These results reveal that recipient conditions and microenvironments represent key factors for successful cell therapy using BMCs.}, Author = {Terai, Shuji and Sakaida, Isao and Yamamoto, Naoki and Omori, Kaoru and Watanabe, Tomomi and Ohata, Shinya and Katada, Toshiaki and Miyamoto, Koji and Shinoda, Koh and Nishina, Hiroshi and Okita, Kiwamu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0021-924X}, Journal = {J Biochem (Tokyo)}, Keywords = {Research Support, Non-U.S. Gov't;Cell Differentiation;Cell Culture Techniques;Animals;Cells, Cultured;Cell Movement;Fibrosis;Liver;Mice, Inbred C57BL;11 Glia;Time Factors;Microscopy, Fluorescence;Green Fluorescent Proteins;Bone Marrow Cells;Mice;Luminescent Proteins;Immunohistochemistry;Hepatocytes;Albumins;Carbon Tetrachloride}, Medline = {22969963}, Month = {10}, Nlm_Id = {0376600}, Number = {4}, Organization = {Department of Molecular Science &Applied Medicine (Gastroenterology &Hepatology), Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505. terais\@yamaguchi-u.ac.jp}, Pages = {551-8}, Pubmed = {14607982}, Title = {An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes}, Uuid = {78E76360-71DD-493C-B04E-06D1373809AE}, Volume = {134}, Year = {2003}} @article{Terman:1996, Abstract = {Thalamic reticularis, thalamocortical, and cortical cells participate in the 7-14-hz spindling rhythm of early sleep and the slower delta rhythms of deeper sleep, with different firing patterns. In this case study, showing the interactions of intrinsic and synaptic properties, a change in the conductance of one kind of cell effectively rewires the thalamocortical circuit, leading to the transition from the spindling to the delta rhythm. The two rhythms make different uses of the fast (GABAA) and slow (GABAB) inhibition generated by the thalamic reticularis cells.}, Author = {Terman, D. and Bose, A. and Kopell, N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {24 Pubmed search results 2008;Mathematics;Electroencephalography;Delta Rhythm;21 Neurophysiology;Models, Neurological;research support, u.s. gov't, non-p.h.s.;research support, u.s. gov't, p.h.s.;Humans;Nerve Net;Cerebral Cortex;Sleep;Thalamus}, Month = {12}, Nlm_Id = {7505876}, Number = {26}, Organization = {Department of Mathematics, Boston University, MA 02215, USA.}, Pages = {15417-22}, Pubmed = {8986826}, Title = {Functional reorganization in thalamocortical networks: transition between spindling and delta sleep rhythms}, Uuid = {14DB1B5B-D532-4728-B5D5-0A16568A3B00}, Volume = {93}, Year = {1996}, url = {papers/Terman_ProcNatlAcadSciUSA1996.pdf}} @article{Tettoni:1998, Abstract = {In order to determine to what extent the terminal arbors of phylogenetically and functionally distant axons are constructed according to common rules, we have compared visual callosal axons in cats (CCC axons) with thalamocortical axons to the whisker representation in mice (MTC axons). Both similarities and differences were found. Maximal order of branching, branching angles, topological distribution of branches and boutons are similar for all axons, indicating strong constraints in arbor formation. CCC and MTC axons are indistinguishable for total arbor length and number of branches, although these parameters can vary across individual axons of each group. MTC axons have longer and bouton-richer end-branches (the 'transmission compartment') while, in CCC axons, proximal, boutonless branches (the 'conduction compartment') predominate. Therefore, the two classes of axons appear to be specialized for performing different types of operations, in agreement with the available electrophysiological data and computer simulations. Differences in the length of branches were also observed between MTC axons of normal and 'barrelless' mice, suggesting that this parameter can be regulated by conditions at the terminal sites.}, Author = {Tettoni, L. and Gheorghita-Baechler, F. and Bressoud, R. and Welker, E. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Cell Differentiation;Presynaptic Terminals;Animals;Neural Pathways;Comparative Study;Phenotype;Visual Pathways;Axons;Vibrissae;Not relevant;11 Glia;Models, Anatomic;Mice, Neurologic Mutants;Computer Simulation;Thalamus;Support, Non-U.S. Gov't;Cerebral Cortex;Mice;Cats;Models, Neurological;Corpus Callosum}, Medline = {98429184}, Month = {9}, Nlm_Id = {9110718}, Number = {6}, Organization = {Institut de Biologie Cellulaire et de Morphologie, Universit{\'e} de Lausanne, Switzerland.}, Pages = {543-52}, Pubmed = {9758217}, Title = {Constant and variable aspects of axonal phenotype in cerebral cortex}, Uuid = {60E553F6-2E79-420D-B01C-95CA6DD8B0EF}, Volume = {8}, Year = {1998}} @article{Tettoni:1996, Abstract = {In order to analyze the structural organization of complex axonal arbors reconstructed from histological serial sections, and to investigate the functional implications of their geometrical properties, we developed software providing the following facilities: (1) direct importation of data files generated by a commercially available 3-D light-microscopic reconstruction system, including routine procedures for identification and correction of data acquisition errors; (2) real-time 3-D rotations of the arbors in the stack of serial sections; (3) multiple interactive display modes; (4) possibility of modifying diameter and/or connectivity of different branches; (5) simulation of the invasion of the arbor by a single action potential initiated at any chosen point, and visualization of spatio-temporal profiles of activation; (6) extraction of quantitative data converted to standard file formats compatible with available mathematical software. All these tools can be applied to single or multiple axons, individually or simultaneously. The software, called Maxsim, is a highly flexible C-written program running on graphical workstations using the UNIX operating system and X-Window environment.}, Author = {Tettoni, L. and Lehmann, P. and Houzel, J. C. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Neurosciences;Software;Not relevant;11 Glia;Support, Non-U.S. Gov't;Animals;Neurons;Axons}, Medline = {97001527}, Month = {7}, Nlm_Id = {7905558}, Number = {1}, Organization = {Institut d'Anatomie, Lausanne, Switzerland.}, Pages = {1-9}, Pii = {016502709500095X}, Pubmed = {8844519}, Title = {Maxsim, software for the analysis of multiple axonal arbors and their simulated activation}, Uuid = {47C26FEF-2C85-40C4-8B4B-CF8E56B0D1EA}, Volume = {67}, Year = {1996}} @article{Thalmeier:2001, Abstract = {BACKGROUND: CD34(-) stem cells are apparently the earliest progenitors of hematopoiesis and mesenchymal tissues. The majority of those progeny rests in the BM as fibroblast-like cells, but can also circulate the peripheral blood. Nevertheless, CD34(-), fibroblast-like cells can be isolated from BM aspirates and PBMC, mediated by their ability to adhere to the plastic surface of tissue culture flasks. In standard colony assays, CD34(-), fibroblast-like cells produce a significant number of colony-forming-units (CFUs), mainly CFU-F (fibroblast). METHODS: Despite advanced cell-culture techniques and the application of various growth factors, the life span of those multipotent stem cells is limited. Therefore, we immortalized and cloned fibroblast-like, CD34(-) stem cells and used retroviral constructs containing the green-fluorescence protein (GFP) to determine the gene-transfer efficiency and their use for gene marking prior to transplantation into NOD/SCID mice. RESULTS: We could demonstrate a highly efficient retroviral gene transfer into those immortalized CD34(-), fibroblast-like hematopoietic cells (up to 95\%transduced cells), maintaining their ability to produce CFUs, as well as a distinct organ distribution after transplantation into the recipient animals, functioning as SCID-repopulating cells (SRC). Transplanted cells could be detected in the BM, as well as other parenchymal organs, such as the lung, liver, skin, small intestine and brain. DISCUSSION: CD34(-), fibroblast-like progenitor cells can give rise to hematopoietic progeny, but also home to mesenchymal organ sites in recipient animals. There is increasing evidence that pluripotent CD34(-) stem cells can be isolated from various sources and still maintain their capabilities to generate progeny of different tissues. This could be a promising approach to using peripheral-blood derived stem cells for cellreplacement therapy and tissue engineering.}, Author = {Thalmeier, K. and Huss, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1465-3249}, Journal = {Cytotherapy}, Keywords = {Lung;Transduction, Genetic;Mice, Inbred NOD;Animals;Viscera;Cell Line, Transformed;Fibroblasts;Female;Indicators and Reagents;Antigens, CD34;Retroviridae;11 Glia;Green Fluorescent Proteins;Genetic Vectors;Hematopoietic Stem Cell Transplantation;Male;Bone Marrow Cells;Gene Transfer Techniques;Mice;Hematopoietic Stem Cells;Luminescent Proteins;Graft Survival;Dogs;Spleen;Research Support, Non-U.S. Gov't}, Medline = {22162136}, Nlm_Id = {100895309}, Number = {4}, Organization = {Institute of Pathology, University of Munich, Germany.}, Pages = {245-51}, Pubmed = {12171712}, Title = {Highly efficient retroviral gene transfer into immortalized CD34(-) cells and organ distribution after transplantation into NOD/SCID mice}, Uuid = {30A39EDD-A11C-4DC8-8765-10CA222FC8F9}, Volume = {3}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1080/146532401317070871}} @article{Thanos:1992, Abstract = {Understanding of neuron-glial interactions in neurodegenerative diseases remains limited, but is of crucial importance for unravelling the etiology of such disorders both in humans and in animals. The present work employed a new, function-dependent technique for examining the role of microglia in rats afflicted with inherited retinal photoreceptor degeneration (strain: royal college of surgeons, RCS). In this rat strain, which served as a surrogate for human inherited retinal photoreceptor dystrophy, the optic nerve was cut and the ganglion cells were retrogradely labelled with the fluorescent dye 4Di-10ASP. The experiment was performed under three different conditions: (1) at the 50th day of postnatal age (P50) when there is ongoing degeneration of photoreceptor cells, (2) at P110 when most photoreceptors were degenerated and (3) at P50 in non-dystrophic rats of the Sprague-Dawley strain. After axotomy-induced ganglion cell death and labelling of activated microglia by phagocytosis of the ganglion cell debris, this study monitored whether the labelled and therefore identifiable microglial cells within the severed ganglion cell layer (GCL) are prompted to migrate and to participate in phagocytosis of debris produced within the endogenously degenerating photoreceptor cell layer (PRL). Massive migration of microglial cells from the GCL to the PRL occurred in dystrophic animals with optic nerve transection at P50. Double-labelling of microglial cells with the fluorescent dye ingested within the GCL and with lipofuscin ingested within the PRL indicated the ability of these cells to perform double-phagocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Thanos, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Axons;Retina;Neuroglia;Rats, Sprague-Dawley;Nerve Degeneration;Retinitis;Rats;Photoreceptors;Not relevant;Retinal Degeneration;11 Glia;Retinal Ganglion Cells;Animals;Disease Models, Animal;Phagocytosis;Rats, Inbred Strains;Support, Non-U.S. Gov't}, Medline = {93007098}, Month = {8}, Nlm_Id = {0045503}, Number = {1}, Organization = {Department of Ophthalmology, University of T{\"u}bingen, School of Medicine, FRG.}, Pages = {21-8}, Pubmed = {1393569}, Title = {Sick photoreceptors attract activated microglia from the ganglion cell layer: a model to study the inflammatory cascades in rats with inherited retinal dystrophy}, Uuid = {F13F51D0-1D7A-4A42-AD24-2F8B20B2238F}, Volume = {588}, Year = {1992}} @article{Thanos:1991, Abstract = {The interactions between dying neurons and phagocytotic cells within the developing and injured retina remain controversial. The present work explored the role of microglia and investigated whether so-called resident microglial cells are permanently responsible for removing cell debris whenever it is produced. As a first goal, I characterized some quantitative and morphometric features of the small ipsilateral retinocollicular projections and analysed the permanent function of phagocytosing microglia with these projections as a paradigm. To achieve this, I combined the fluorescent dyes Dil and 4Di-10ASP, both of which persist in the labelled ganglion cells after injection into the superior colliculus (SC), and retrograde labelling. After neuronal degradation, the dyes accompany the degradation products, become interiorized and then persist within the phagocytosing microglia. Consequently, early labelling of microglial cells can be assessed by injecting one dye into the SC during the first postnatal day of life, that is, prior to advanced natural neuronal cell death. Labelling of the remaining ipsilaterally projecting neurons with the second dye following intraorbital axotomy in adulthood and during subsequent neuronal death would therefore result in double labelling of some microglial cells, if these were involved in phagocytosis during both the natural and the induced phases of neuronal degradation. The ganglion cells which survived natural neuronal cell death remained fluorescent for 3 months after labelling with either dye on the day of the animal's birth, indicating that both fluorescent probes persisted within neurons. Quantitatively, 1770+/-220 ganglion cells/mm2 were labelled within the contralateral retina and a total population of 1442+/-120 cells/retina were observed within the periphery of the inferior/temporal quadrant of the ipsilateral retina. A smaller, ipsilateral projection of 150+/-24 cells/retina was uniformly scattered throughout the rest of the retinal surface. Transient projections of ganglion cells to either the contralateral or the ipsilateral colliculi and death of labelled ganglion cells during the first postnatal days resulted in labelling of 210+/-36 microglial cells/mm2 within the contralateral retina and a total number of 800+/-120 cells/retina within the inferior/temporal and 200+/-22 cells/retina within the rest of the retina. These labelled microglial cells were observed in adulthood and indicated that after taking away the neuronal cell debris they persisted within the retinal tissue. The small number of prelabelled ganglion cells which formed persistent ipsilateral projections until adulthood were axotomized by transecting the optic nerve, and resulted in additional labelling of microglial cells with the second fluorescent dye as well. Double-labelled microglia were observed within the inferior/temporal quadrant (3500+/-240 cells/retina) and to a lesser extent (340+/-40 cells/retina) scattered over the entire retinal surface. The chronotopological sequence of microglial labelling paralleled that of ganglion cell degeneration. Injection of protease inhibitors into the vitreous body during optic nerve transection retarded retrograde glial cell degeneration, probably by blocking microglial proteases. The results directly proved that the same microglial cells which remove neuronal cell debris in the postnatal retina were reactivated later in life to proteolytically degrade and then phagocytose neurons which had altered because of the axotomy.}, Author = {Thanos,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Not relevant;Get paper from library;11 Glia;24 Pubmed search results 2008}, Nlm_Id = {8918110}, Number = {12}, Organization = {Research Laboratory, Department of Ophthalmology, University of T{\"u}bingen School of Medicine, Schleichstrasse 12, 7400 T{\"u}bingen, FRG.}, Pages = {1189-1207}, Pii = {ejn_03121189}, Pubmed = {12106219}, Title = {The Relationship of Microglial Cells to Dying Neurons During Natural Neuronal Cell Death and Axotomy-induced Degeneration of the Rat Retina}, Uuid = {F942FBD5-A8BF-4079-A40B-A0E0B41ED818}, Volume = {3}, Year = {1991}} @article{Thanos:1992a, Abstract = {The present work was undertaken to assess the fate of ganglion cell debris in the axotomized retina of adult rats and employed a new technique to label phagocytosing microglia via the internalized material. In the main experiment, transection axotomy was performed on the intraorbital segment of the optic nerve, and a fast-transported, vital fluorescent styryl dye (4Di-10ASP) was deposited at the ocular stump of the nerve in order to pre-label retrogradely the ganglion cells destined to die because of the axotomy. Optic nerve transection resulted in progressive degradation of ganglion cell axons, perikarya, and dendrites within the retina and in release of fluorescent material, which was then incorporated into cells identified as microglia. No other retinal cells stained, although astrocytes and M{\"u}ller's cells also responded to neuron degeneration by accumulating glial fibrillary acidic protein. Incorporation of labelled material into microglia topo-chronologically paralleled the ganglion cell degeneration starting within the optic fibre layer (OFL) and proceeding towards the ganglion cell layer (GCL) and the inner plexiform layer (IPL) of the affected retina. Long-term labelling of microglia monitored up to 3 months after optic nerve transection indicated that labelled microglial cells persisted within the retina. Microglia displayed a strong territorial arrangement within the GCL and IPL, and staggered, bilaminated distribution in both layers. These studies directly prove that microglia in the retina can be transcellularly labelled during traumatic degeneration of ganglion cells. The findings suggest that microglial cells play an important role in axotomy-induced wound healing and removal of cell debris.}, Author = {Thanos, S. and Pavlidis, C. and Mey, J. and Thiel, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0014-4835}, Journal = {Exp Eye Res}, Keywords = {Fluorescent Dyes;Thiamine Pyrophosphatase;Nerve Degeneration;Animals;Phagocytosis;Rats;Female;Cell Count;Optic Nerve;Rats, Inbred Strains;Staining and Labeling;Not relevant;Get paper from library;Time Factors;11 Glia;Dendrites;Support, Non-U.S. Gov't;Carbocyanines;Retinal Ganglion Cells}, Medline = {93011730}, Month = {7}, Nlm_Id = {0370707}, Number = {1}, Organization = {Department of Ophthalmology, University of T{\"u}bingen, School of Medicine, Germany.}, Pages = {101-17}, Pubmed = {1383017}, Title = {Specific transcellular staining of microglia in the adult rat after traumatic degeneration of carbocyanine-filled retinal ganglion cells}, Uuid = {71778C4C-8AE1-4E25-917B-BE569C0FAE84}, Volume = {55}, Year = {1992}, url = {papers/Thanos_ExpEyeRes1992.PDF}} @article{Thanos:1993, Abstract = {To monitor the cascade of events initiated by injury of adult neurons, and to explore whether and how neighboring microglial cells contribute to the degradation of lesioned neurons, axotomy-induced ganglion cell degeneration was investigated in adult rats. Suppression of macrophage and microglia activity during the weeks following transection of the optic nerve was performed with the immunoglobulin-derived tripeptide Thr-Lys-Pro, which is a macrophage inhibitory factor (MIF) and retards the activity of cells of monocytic origin. Single or repeated injection of MIF into the vitreous body during and after transection of the optic nerve resulted in significant retardation of axotomy-induced ganglion cell degradation in the retina as detected by specific labeling with the retrogradely transported fluorescent dye 4Di-10ASP. MIF specifically altered the morphology of labeled microglial cells from a ramified to an oval, less ramified shape, indicating that these cells were targets of its activity. Injection of the tetrapeptide macrophage stimulating factor, also known as tuftsin (Thr-Lys-Pro-Arg), revealed effects opposite to those described for the MIF: it increased the number of labeled microglial cells and enhanced the devastating effects of axotomy on ganglion cells. The viability of rescued ganglion cells in retinas treated with the various drugs was assessed both in vivo and in vitro. (1) Intravitreal injection of MIF to prevent degradation of neurons combined with transplantation of autologous peripheral nerve grafts, which facilitate regrowth of the transected neurites, revealed that significantly more ganglion cells contributed to axonal regeneration (17.1\%) than in untreated controls (9.5\%). (2) Explantation of retinas that were pretreated with MIF in situ revealed higher incidence of axonal outgrowth in organ cultures than untreated control explants or retinas treated with either the basic fibroblast growth factor or brain-derived neurotrophic factor. The present results demonstrate that axotomy initializes a cascade of microglia-mediated autodestructive retinal responses, which culminate in degradation of "sick," but obviously viable neurons. We postulate that the retinal microglial system has a key role in recognizing and eliminating severed neurons.}, Author = {Thanos, S. and Mey, J. and Wild, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Research Support, Non-U.S. Gov't;Nerve Degeneration;Animals;Macrophages;Rats;Oligopeptides;Female;Denervation;Rats, Sprague-Dawley;Optic Nerve;Axons;11 Glia;Nerve Regeneration;Axonal Transport;Macrophage Migration-Inhibitory Factors;Neuroglia;Tuftsin;24 Pubmed search results 2008;Amino Acid Sequence;Molecular Sequence Data;Retinal Ganglion Cells}, Medline = {93147920}, Month = {2}, Nlm_Id = {8102140}, Number = {2}, Organization = {Department of Ophthalmology, University of T{\"u}bingen, School of Medicine, Germany.}, Pages = {455-66}, Pubmed = {7678855}, Title = {Treatment of the adult retina with microglia-suppressing factors retards axotomy-induced neuronal degradation and enhances axonal regeneration in vivo and in vitro}, Uuid = {54E4FFC1-8FE6-40EC-A9C0-81F5FC086B51}, Volume = {13}, Year = {1993}} @article{Thanos:1994, Abstract = {The nature of the interactions between dying neurons and microglial cells within the developing and injured CNS remains controversial. A new technique for labelling microglial cells is available, which enables further studies of such interactions in a direct way. The value of the method relies on retrograde filling of neurons with vital fluorescent dye, subsequent degeneration of the neurons due to either naturally occurring cell death or as the result of axotomy, and phagocytotic removal of the fluorescent cell debris by microglial cells, which thus become identifiable. The fluorescent dye can be visualized in whole-mounted tissue or after sectioning. Photoconversion of the dye into electron-dense material permits examination of the microglial and dying ganglion-cell interactions at the ultrastructural level. This new principle of the function-dependent, selective fluorescent labelling of phagocytosing microglial cells, which might now be extended to other dyes and to other neurodegenerative models, promises to shed light onto the function of microglial cells within the brain.}, Author = {Thanos, S. and Kacza, J. and Seeger, J. and Mey, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {23 Technique;Alpha;Not relevant;Fluorescent Dyes;11 Glia;Microglia;Microscopy, Fluorescence;Retinal Ganglion Cells;Neurology;Animals;Phagocytosis;G;24 Pubmed search results 2008}, Medline = {94337417}, Month = {5}, Nlm_Id = {7808616}, Number = {5}, Organization = {Dept of Ophthalmology, University of T{\"u}bingen, School of Medicine, Germany.}, Pages = {177-82}, Pubmed = {7520197}, Title = {Old dyes for new scopes: the phagocytosis-dependent long-term fluorescence labelling of microglial cells in vivo}, Uuid = {9187B582-3592-4B4F-90D2-9D8D60C3EE18}, Volume = {17}, Year = {1994}} @article{Thery:1994, Abstract = {Brain macrophages (BM), a subpopulation of microglia, have the ability to kill neurons by producing reactive oxygen intermediates. Cocultures of neurons and macrophages derived from the cerebral cortex of rat embryos were used to look for regulation of BM neurotoxicity. Isoproterenol (10(-7) M), a beta-adrenergic agonist, induced a significant inhibition of BM neurotoxicity and this effect was abolished in the presence of propranolol, a beta-adrenergic antagonist. BM neurotoxicity was also reduced in the presence of prostaglandin E2 (10(-8), 10(-6) M), a metabolite derived from arachidonic acid. These results suggest endogenous mechanisms of neuroprotection operating either during development or following lesions.}, Author = {Th{\'e}ry, C. and Dobbertin, A. and Mallat, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Down-Regulation;Propranolol;Support, Non-U.S. Gov't;Adrenergic beta-Agonists;Rats;Reactive Oxygen Species;Not relevant;11 Glia;Dinoprostone;Cell Death;Macrophages;Isoproterenol;Microtubule-Associated Proteins;Brain;Neurons;Animals}, Medline = {95048682}, Month = {8}, Nlm_Id = {8806785}, Number = {4}, Organization = {INSERM U.114, Chaire de Neuropharmacologie, Coll\`{e}ge de France, Paris, France.}, Pages = {383-6}, Pubmed = {7960041}, Title = {Downregulation of in vitro neurotoxicity of brain macrophages by prostaglandin E2 and a beta-adrenergic agonist}, Uuid = {7DDB487C-FE27-43C0-A4F4-79776DE7ABB6}, Volume = {11}, Year = {1994}} @article{Thery:1990, Abstract = {We have investigated the expression of macrophage-colony stimulating factor (M-CSF) gene in mouse brain during development. Northern blot analysis of cerebral RNA evidenced a 4.5-kb M-CSF transcript from day 14 of gestation until 2 weeks after birth. The cell type responsible for this transcription was studied using in vitro cell cultures. The 4.5-kb M-CSF transcript was found both in astrocyte primary cultures and in immortalized astrocytic cell lines. M-CSF mRNA was also detected in lipopolysaccharide-stimulated brain macrophage cultures. These results suggest that M-CSF is involved in the outgrowth of microglia during ontogenesis.}, Author = {Th{\'e}ry, C. and H{\'e}tier, E. and Evrard, C. and Mallat, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Embryo and Fetal Development;Macrophage Colony-Stimulating Factor;Cerebral Cortex;Animals;Nucleic Acid Hybridization;Gene Expression Regulation;Astrocytes;11 Glia;Colony-Stimulating Factors;Support, Non-U.S. Gov't;Molecular Weight;Cells, Cultured;RNA, Messenger;Mice}, Medline = {90294329}, Month = {5}, Nlm_Id = {7600111}, Number = {1}, Organization = {Inserum U.114, Chaire de Neuropharmacologie, Coll\`{e}ge de France, Paris.}, Pages = {129-33}, Pubmed = {2193167}, Title = {Expression of macrophage colony-stimulating factor gene in the mouse brain during development}, Uuid = {373B1E3D-94A4-4CC6-934E-D13F18CF2AF1}, Volume = {26}, Year = {1990}} @article{Thinakaran:1993, Abstract = {Skeletal myoblasts undergo terminal differentiation when maintained under low-mitogen conditions. We have examined the expression of c-jun, one of the growth-factor-inducible immediate-early genes, during myogenic differentiation of L6 myoblasts. The steady-state levels of c-jun mRNA, c-Jun polypeptide, and activator protein 1 binding activity were not markedly altered in L6 cells undergoing myogenic differentiation. Although expression of c-jun is induced by serum mitogens in fibroblasts and other cell lines, addition of high serum to proliferating myoblasts resulted in the activation of another immediate early gene junB, but not c-jun mRNA expression. These results indicate that regulation of c-jun may differ from that of other immediate early genes in L6 cells. Manipulation of myogenesis by exposing L6 cells to dimethyl sulfoxide also suggested that expression of myogenin and muscle differentiation could occur in the presence of high levels of c-Jun. Furthermore, expression of c-jun from Moloney murine leukaemia viral long-terminal repeat in transfected L6 cells confirmed that constitutive expression of c-jun does not interfere with myogenesis in L6 myoblasts. Therefore, regulation of c-jun expression in rat L6 cells differs from that in the mouse C2 cell line. 0829-8211 Journal Article}, Author = {Thinakaran, G. and Bag, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Biochem Cell Biol}, Keywords = {Cell Differentiation/drug effects/*genetics;Animals;Base Sequence;Rats;Transfection;Repetitive Sequences, Nucleic Acid;Muscles/*cytology;*Gene Expression;Moloney murine leukemia virus/genetics;*Genes, jun;Proto-Oncogene Proteins c-jun/metabolism;DNA/metabolism;EE, DMSO, abstr;08 Aberrant cell cycle;Myogenin/genetics;Dimethyl Sulfoxide/pharmacology;Cell Line;Half-Life;Support, Non-U.S. Gov't;RNA, Messenger/metabolism;Blood;Transcription, Genetic}, Number = {5-6}, Organization = {Department of Molecular Biology and Genetics, University of Guelph, ON, Canada.}, Pages = {260-9}, Pubmed = {8274267}, Title = {Expression of the protooncogene c-jun is maintained during myogenic differentiation in rat L6 myoblasts}, Uuid = {E16197A5-16D8-471E-966A-5BD7AD63AC02}, Volume = {71}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8274267}} @article{Thom:2004, Abstract = {PURPOSE: Grey matter heterotopia are well-defined malformations of the cortex often associated with severe epilepsy. Defects have been identified in genes, including DCX and FLN1, that influence radial migration of postmitotic cells from the ventricular zone to the cortical plate. A proportion of cortical gamma-aminobutyric acid (GABA)-containing interneurons may arise from the ganglionic eminence of the ventral telencephalon. We aimed to identify the subtypes and localisation of interneurons within grey matter heterotopia relative to cortex. METHODS: By using quantitative immunohistochemistry, we studied the density and distribution of interneurons within six cases of grey matter heterotopia in postmortem tissue from patients with epilepsy. RESULTS: In many cases, a suggestion of focal rudimentary laminar arrangement and small reelin-positive cells was identified within the heterotopia. Immunohistochemistry for glutamic acid decarboxylase(65/57), parvalbumin, calbindin, and calretinin showed inhibitory neurons of all subtypes represented within the heterotopia, and of normal morphology. The mean densities of interneurons were overall similar to those of the overlying cortex, but the interneurons showed less organisation and were more randomly orientated compared with cortex. CONCLUSIONS: Interneurons within heterotopia probably arise from the ventricular zone, but their abnormal local organization may influence the epileptogenicity of these lesions.}, Author = {Thom, Maria and Martinian, Lillian and Parnavelas, John G. and Sisodiya, Sanjay M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {gamma-Aminobutyric Acid;10 Development;Research Support, Non-U.S. Gov't;Child, Preschool;Humans;Comparative Study;21 Epilepsy;Female;Epilepsy;Cell Count;Child;Serine Endopeptidases;Cell Adhesion Molecules, Neuronal;Male;Extracellular Matrix Proteins;Nervous System Malformations;Cerebral Cortex;21 Neurophysiology;10 genetics malformation;Adult;Interneurons;24 Pubmed search results 2008;Immunohistochemistry;Nerve Tissue Proteins;Choristoma;Adolescent}, Month = {8}, Nlm_Id = {2983306R}, Number = {8}, Organization = {Department of Clinical and Experimental Epilepsy, Institute of Neurology, University College London, London, United Kingdom. M.Thom\@ion.ucl.ac.uk}, Pages = {916-23}, Pii = {EPI46603}, Pubmed = {15270756}, Title = {Distribution of cortical interneurons in grey matter heterotopia in patients with epilepsy}, Uuid = {51A154DA-0409-47DE-9149-EFDC90C617DF}, Volume = {45}, Year = {2004}, url = {papers/Thom_Epilepsia2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.0013-9580.2004.46603.x}} @article{Thomas:1999, Abstract = {Pericytes are a unique cell group intimately associated with the vasculature and that appear to be present in most tissues. Their presence is generally considered to be restricted to the microvessels - arterioles, venules and particularly capillaries, where there is little or no smooth muscle. Morphologically, the pericytes exhibit a small, oval cell body with multiple processes extending for some distance along the vessel axis; these primary processes then give rise to orthogonal secondary branches which encircle the vascular wall. Through this morphology and their close association with the vasculature, the contour of the cells conforms to that of the adjacent vascular element; also, they are usually enclosed within the basal lamina of the microvasculature. While many earlier studies suggested brain pericytes as a source of macrophage activity, recent results substantiate this functional role; these recent findings include the demonstration of macrophage markers, phagocytosis and antigen presentation. Coupled with current knowledge on the entry of lymphoblasts into brain tissue and perivascular areas as potentially being the primary site of cellular interactions for production of immune responses, this places the pericytes in a position to significantly contribute to central nervous system (CNS) immune mechanisms. They may in fact be the population of brain macrophages most instrumental in the initiation of an immune response. Although these cells constitutively express several macrophage properties, they are also capable of up-regulation to display the full range of macrophage functional activity. At least, some of the pericytic macrophages are located on the surface of the basal lamina as opposed to completely within it; however, their potential transformation into microglia of the parenchyma remains an open issue. In addition to their function as macrophages, pericytes appear to serve a host of other functional roles. They are contractile and seem to serve as a smooth muscle equivalent in the capillaries performing vasoconstriction; they regulate endothelial cell properties and contribute to the stability and maintenance of blood vessels; and they appear to directly participate in coagulation through the extrinsic pathway. Also, pericytes have been suggested to be pluripotential and serve as precursors for a variety of other cell types. From these functional roles, comes their involvement in various disease processes. In association with the macrophage function, they are involved in numerous autoimmune and infectious diseases. Through their vascular role, they are involved in diabetic retinopathy and inflammation. Also, the pericytes appear to have involvement in Alzheimer's as well as other diseases. Thus, these cells are presented not only as macrophages but as a group with broad functional activities and significant potential for contributing to disease states.}, Author = {Thomas, W. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0165-0173}, Journal = {Brain Res Brain Res Rev}, Keywords = {Endothelium, Vascular;Pericytes;Rats;Research Support, U.S. Gov't, P.H.S.;11 Glia;Macrophages;Animals;Brain;Mice;review;Humans}, Medline = {20079001}, Month = {12}, Nlm_Id = {8908638}, Number = {1}, Organization = {Department of Biological Sciences, 308 Hovey Hall, Illinois State University, Normal, IL 61790-4000, USA.}, Pages = {42-57}, Pii = {S0165017399000247}, Pubmed = {10611494}, Title = {Brain macrophages: on the role of pericytes and perivascular cells}, Uuid = {C4DF02CF-A154-4521-8EC3-A8FEEC24F48D}, Volume = {31}, Year = {1999}} @article{Thomas:1996, Abstract = {The subependymal zone (SEZ) of the lateral ventricle of adult rodents has long been known to be mitotically active. There has been increased interest in the SEZ, since it has been demonstrated that neuroepithelial stem cells residing there generate neurons in addition to glia in vitro. In the present study, we have examined parasagittal sections of the adult mouse brain using immunocytochemistry for extracellular matrix (ECM) molecules (tenascin and chondroitin sulfate- containing proteoglycans), glial fibrillary acidic protein (GFAP, a cytoskeletal protein prominently expressed by immature and reactive astrocytes), RC-2 (a radial glial and immature astrocyte cytoskeletal marker), TuJ1 (a class III beta-tubulin isoform expressed solely by postmitotic and adult neurons), nestin (a cytoskeletal protein associated with stem cells), neuron-specific enolase, and bromodeoxyuridine (BrdU, which is taken up by dividing cells). Our results demonstrate that a population of young neurons reside within an ECM-rich, GFAP-positive astrocyte pathway from the rostral SEZ all the way into the olfactory bulb. Furthermore, BrdU labeling studies indicate that there is a high level of cell division along the entire length of this path, and double-labeling studies indicate that neurons committed to a neuronal lineage (i.e., TuJ1+) take up BrdU (suggesting they are in the DNA synthesis phase of the cell cycle), again along the entire length of the SEZ "migratory pathway."Thus, the SEZ appears to retain the ability to produce neurons and glia throughout the life of the animal, functioning as a type of "brain marrow."The implications of these findings are discussed in relation to the role that such a glial/ ECM-rich boundary (as seen in the embryonic cortical subplate and other developing areas) may play in: confining the migratory populations and maintaining them in a persistent state of immaturity; facilitating their migration to the olfactory bulb, where they are incorporated into established adult circuitries; and potentially altering SEZ cell cycle dynamics that eventually lead to cell death.}, Author = {Thomas, L. B. and Gates, M. A. and Steindler, D. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Glia}, Keywords = {Astrocytes/*physiology;02 Adult neurogenesis migration;Neurons/*physiology;Extracellular Matrix/*physiology;Immunohistochemistry;Brain/*anatomy &histology;Animal;Mice, Inbred ICR;Support, U.S. Gov't, P.H.S.;B abstr;Cell Division/*physiology;Support, Non-U.S. Gov't;Mice;Neural Pathways/*anatomy &histology}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis 38163, USA.}, Pages = {1-14.}, Title = {Young neurons from the adult subependymal zone proliferate and migrate along an astrocyte, extracellular matrix-rich pathway}, Uuid = {03B34F82-139C-40D9-B918-1C561E6AD7D5}, Volume = {17}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8723838}} @article{Thomas:2007, Abstract = {Factors modulating neurogenesis may contribute to the pathophysiology of affective disorders such as major depression. Environmental stressors in animal models have been proposed to alter neurogenesis, suggesting a mechanism for this contribution. The effect of an acute psychosocial stressor on either proliferation or survival (immediate, short term, and long term) was examined along with subsequent neuronal differentiation in the hippocampus of adult male Sprague Dawley rats. Subjects were exposed to a widely used social dominance paradigm that elicits behavioral and physiological responses to an acute psychosocial stressor. This social dominance paradigm may mimic human relational stress more realistically than laboratory stressors and provides a socially relevant model. We found that exposure to an acute psychosocial stressor at the time of cell generation resulted in a decreased number of newly generated cells in the hippocampus. By using sequential thymidine analog administration to provide temporal discrimination of DNA replication, we showed that short-term survival but not initial proliferation or immediate survival was altered in response to stress. Furthermore, we determined that stress experienced subsequent to proliferation also diminished long-term survival of cells. Thus, an acute episode of a social stress produces long-lasting effects on the incorporation of new hippocampal neurons by reducing their survival.}, Author = {Thomas, Rosanne M. and Hotsenpiller, Gregory and Peterson, Daniel A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {02 Adult neurogenesis migration;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8102140}, Number = {11}, Organization = {Neural Repair and Neurogenesis Laboratory, Department of Neuroscience, The Chicago Medical School at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois 60064, USA.}, Pages = {2734-43}, Pii = {27/11/2734}, Pubmed = {17360895}, Title = {Acute psychosocial stress reduces cell survival in adult hippocampal neurogenesis without altering proliferation}, Uuid = {BE14073E-F66E-4C7F-B9A0-8805BC384D87}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3849-06.2007}} @article{Thomson:2003, Abstract = {This review summarizes the local circuit, interlaminar connections in adult mammalian neocortex. These were first demonstrated with anatomical techniques, which indicate some of the exquisite spatial precision present in the circuitry. Details, such as the class(es) of neurons targeted by some of these projections, have begun to be added in studies that combine paired/triple intracellular recordings with dye-filling of connected neurons. Clear patterns are emerging from these studies, with 'forward' projections from layer 4 to 3 and from 3 to 5 targeting both selected pyramidal cells and interneurons, while 'back' projections from layer 5 to 3 and from 3 to 4 target only interneurons. To place these data in a wider context, the major afferent inputs to and efferent outputs from each of the layers are discussed first.}, Author = {Thomson, Alex M. and Bannister, A. Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {24 Pubmed search results 2008;Dendrites;Research Support, Non-U.S. Gov't;21 Neurophysiology;Cats;Efferent Pathways;Feedback;Pyramidal Cells;Neocortex;Vision;Interneurons;Afferent Pathways;Animals;Humans;Nerve Net;review;Thalamus}, Medline = {22354036}, Month = {1}, Nlm_Id = {9110718}, Number = {1}, Organization = {Department of Physiology, Royal Free and University College Medical School, Rowland Hill Street, London NW3 2PF, UK. alext\@rfc.ucl.ac.uk}, Pages = {5-14}, Pubmed = {12466210}, Title = {Interlaminar connections in the neocortex}, Uuid = {88C57EE0-2715-48A6-9F14-D6FC873B4E5F}, Volume = {13}, Year = {2003}, url = {papers/Thomson_CerebCortex2003.pdf}} @article{Thorne:2006, Abstract = {Diffusion within the extracellular space (ECS) of the brain is necessary for chemical signaling and for neurons and glia to access nutrients and therapeutics; however, the width of the ECS in living tissue remains unknown. We used integrative optical imaging to show that dextrans and water-soluble quantum dots with Stokes-Einstein diameters as large as 35 nm diffuse within the ECS of adult rat neocortex in vivo. Modeling the ECS as fluid-filled "pores" predicts a normal width of 38-64 nm, at least 2-fold greater than estimates from EM of fixed tissue. ECS width falls below 10 nm after terminal ischemia, a likely explanation for the small ECS visualized in electron micrographs. Our results will improve modeling of neurotransmitter spread after spillover and ectopic release and establish size limits for diffusion of drug delivery vectors such as viruses, liposomes, and nanoparticles in brain ECS.}, Author = {Thorne, Robert G. and Nicholson, Charles}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Extracellular Space;Rats, Sprague-Dawley;Rats;Female;Dextrans;Neocortex;Research Support, N.I.H., Extramural;Quantum Theory;Diffusion;Animals;24 Pubmed search results 2008;Nanotechnology;23 Technique}, Month = {4}, Nlm_Id = {7505876}, Number = {14}, Organization = {Department of Physiology and Neuroscience, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.}, Pages = {5567-72}, Pii = {0509425103}, Pubmed = {16567637}, Title = {In vivo diffusion analysis with quantum dots and dextrans predicts the width of brain extracellular space}, Uuid = {FED4DD8C-E767-4CCF-B7D6-BE111677467A}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0509425103}} @article{Threadgill:1997, Abstract = {The acquisition of cell type-specific morphologies is a central feature of neuronal differentiation and has important consequences for nervous system function. To begin to identify the underlying molecular mechanisms, we have explored the role of Rho-related GTPases in the dendritic development of cortical neurons. Expression of dominant negative mutants of Rac or Cdc42, the Rho-inhibitory molecule C3 transferase, or the GTPase-activating protein RhoGAP p190 causes a marked reduction in the number of primary dendrites in nonpyramidal (multipolar) neurons and in the number of basal dendrites in neurons with pyramidal morphologies. Conversely, the expression of constitutively active mutants of Rho, Rac, or Cdc42 leads to an increase in the number of primary and basal dendrites. In cortical cultures, as in vivo, dendritic remodeling leads to an apparent transformation from pyramidal to nonpyramidal morphologies over time. Strikingly, this shift in favor of nonpyramidal morphologies is also inhibited by the expression of dominant negative mutants of Cdc42 and Rac and by RhoGAP p190. These observations indicate that Rho, Rac, and Cdc42 play a central role in dendritic development and suggest that differential activation of Rho-related GTPases may contribute to the generation of morphological diversity in the developing cortex.}, Author = {Threadgill, R. and Bobb, K. and Ghosh, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;GTP-Binding Proteins;Cell Cycle Proteins;Signal Transduction;Animals;Gene Expression Regulation, Developmental;Rats;Transfection;10 Structural plasticity;Phenotype;Proteins;Neocortex;cdc42 GTP-Binding Protein;Cells, Cultured;Beta;Rats, Inbred Strains;RNA, Messenger;Pyramidal Cells;Mutagenesis;GTP Phosphohydrolases;Dendrites;rhoA GTP-Binding Protein;GTPase-Activating Proteins;10 Spiny stellate;Support, Non-U.S. Gov't;Plasmids;Neurotransmitters;Interneurons}, Medline = {97470893}, Month = {9}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.}, Pages = {625-34}, Pubmed = {9331353}, Title = {Regulation of dendritic growth and remodeling by Rho, Rac, and Cdc42}, Uuid = {BA40C7D5-7DE2-4BEE-A133-C6702FCF0CC6}, Volume = {19}, Year = {1997}, url = {papers/Threadgill_Neuron1997.pdf}} @article{Tian:2003, Abstract = {BACKGROUND: Host immune responses to foreign gene products have been shown to lead to the elimination of genetically modified cells, and are a major barrier to successful therapeutic gene therapy. We have shown that immunological tolerance to retrovirally transduced cell surface proteins can be induced by expressing the gene encoding these products in bone marrow derived cells. Here, we investigate if expression of foreign gene products in bone marrow derived cells can be used to induce tolerance to cytoplasmic proteins. METHODS: Balb/c mice were reconstituted with syngeneic bone marrow cells transduced with retrovirus carrying the gene encoding enhanced green fluorescent protein (eGFP), or mock-transduced bone marrow cells. After reconstitution, mice were immunized with cells expressing eGFP, and T cells were tested for the ability to kill eGFP-expressing targets in in vitro cytotoxic T lymphocyte (CTL) assays. RESULTS: T cells from Balb/c mice reconstituted with mock-transduced bone marrow were able to kill target cells expressing eGFP. In contrast, T cells from mice reconstituted with eGFP-transduced bone marrow were unable to kill targets expressing eGFP. In addition, we observed that T cell responses to eGFP in C57BL/6 mice were minimal even under highly immunogenic conditions. CONCLUSIONS: These data suggest that expression of foreign gene products in bone marrow derived cells is capable of inducing T cell tolerance to proteins expressed exclusively in the cytoplasm.}, Author = {Tian, Chaorui and Bagley, Jessamyn and Kaye, Joel and Iacomini, John}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1099-498X}, Journal = {J Gene Med}, Keywords = {T-Lymphocytes;Mice, Inbred BALB C;Animals;Bone Marrow Transplantation;Cytoplasm;Female;Cell Membrane;Recombinant Fusion Proteins;Retroviridae;11 Glia;Green Fluorescent Proteins;Immune Tolerance;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Gene Transfer Techniques;Gene Therapy;T-Lymphocytes, Cytotoxic;Flow Cytometry;Mice;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22616074}, Month = {5}, Nlm_Id = {9815764}, Number = {5}, Organization = {Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, MGH-East, Building 149, 13th St., Boston 02129, USA.}, Pages = {359-65}, Pubmed = {12731084}, Title = {Induction of T cell tolerance to a protein expressed in the cytoplasm through retroviral-mediated gene transfer}, Uuid = {87A96FFB-89E3-4557-97CF-2C37DDA55689}, Volume = {5}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jgm.363}} @article{Tillmann:1994, Abstract = {Retroviruses have been implicated as causative agents of a variety of human diseases including malignancy, immune system dysfunction, and neurologic disorders. Despite the isolation of various retroviral agents from patients suffering from malignant neoplasias and neurologic disorders, only the human T-cell lymphotropic virus type I (HTLV-I) and the human immunodeficiency virus (HIV) have been definitively accepted as etiologic agents of human disease (Hjelle, 1991; Gessain and Gout, 1992; Rosenblatt, 1993). Because of their increasingly defined roles in disease progression, the replication of HTLV-I and HIV is an important focus for understanding the pathogenic processes resulting from viral infection. Of particular interest are the molecular mechanisms by which expression of retroviral genomes is regulated by their regulatory units, the long terminal repeats (LTR), in a manner specific to the cellular targets which they infect.}, Author = {Tillmann, M. and Krebs, F. C. and Wessner, R. and Pomeroy, S. M. and Goodenow, M. M. and Wigdahl, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0960-5428}, Journal = {Adv Neuroimmunol}, Keywords = {Trans-Activation (Genetics);Transcription, Genetic;Transcription Factors;Gene Expression Regulation, Viral;HIV-1;Humans;Base Sequence;Repetitive Sequences, Nucleic Acid;Cells, Cultured;review, tutorial;Human T-lymphotropic virus 1;review;Microglia;Models, Biological;HIV Long Terminal Repeat;Gene Products, tax;Recombinant Fusion Proteins;11 Glia;Research Support, U.S. Gov't, P.H.S.;Genome, Viral;Neuroglia;Molecular Sequence Data;AIDS Dementia Complex}, Medline = {95179422}, Nlm_Id = {9108376}, Number = {3}, Organization = {Department of Microbiology and Immunology, Pennsylvania State University, College of Medicine, Hershey 17033.}, Pages = {305-18}, Pubmed = {7874399}, Title = {Neuroglial-specific factors and the regulation of retrovirus transcription}, Uuid = {DABFF682-D9FC-499C-982C-68AF62CF45AF}, Volume = {4}, Year = {1994}} @article{Tiveron:2006, Abstract = {Most cortical interneurons are generated in the subpallial ganglionic eminences and migrate tangentially to their final destinations in the neocortex. Within the cortex, interneurons follow mainly stereotype routes in the subventricular zone/intermediate zone (SVZ/IZ) and in the marginal zone. It has been suggested that interactions between invading interneurons and locally generated projection neurons are implicated in the temporal and spatial regulation of the invasion process. However, so far experimental evidence for such interactions is lacking. We show here that the chemokine stromal-derived factor 1 (SDF-1; CXCL12) is expressed in the main invasion route for cortical interneurons in the SVZ/IZ. Most SDF-1-positive cells are proliferating and express the homeodomain transcription factors Cux1 and Cux2. Using MASH-1 mutant mice in concert with the interneuron marker DLX, we exclude that interneurons themselves produce the chemokine in an autocrine manner. We conclude that the SDF-1-expressing cell population represents the precursors of projection neurons during their transition and amplification in the SVZ/IZ. Using mice lacking the SDF-1 receptor CXCR4 or Pax6, we demonstrate that SDF-1 expression in the cortical SVZ/IZ is essential for recognition of this pathway by interneurons. These results represent the first evidence for a molecular interaction between precursors of projection neurons and invading interneurons during corticogenesis.}, Author = {Tiveron, Marie-Catherine C. and Rossel, Mireille and Moepps, Barbara and Zhang, Yong Li and Seidenfaden, Ralph and Favor, Jack and K{\"o}nig, Norbert and Cremer, Harold}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Receptors, CXCR4;Signal Transduction;Animals;comparative study;Neural Pathways;Cell Communication;Mice, Transgenic;Cell Movement;Mice, Inbred C57BL;research support, non-u.s. gov't;Cerebral Ventricles;Cerebral Cortex;Neurons;Chemokines, CXC;Mice;Interneurons;24 Pubmed search results 2008;Stem Cells}, Month = {12}, Nlm_Id = {8102140}, Number = {51}, Organization = {Institut de Biologie du D{\'e}veloppement de Marseille Luminy, Centre National de la Recherche Scientifique/Universit{\'e} de Mediterran{\'e}e, 13288 Marseille, France.}, Pages = {13273-8}, Pii = {26/51/13273}, Pubmed = {17182777}, Title = {Molecular interaction between projection neuron precursors and invading interneurons via stromal-derived factor 1 (CXCL12)/CXCR4 signaling in the cortical subventricular zone/intermediate zone}, Uuid = {275C5222-106C-4A4C-80CC-EF344200A075}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4162-06.2006}} @article{Todaro:1972, Author = {Todaro, G. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0090-0028}, Journal = {Nat New Biol}, Keywords = {Tritium;24 Pubmed search results 2008;Mice, Inbred BALB C;Animals;RNA Viruses;15 Retrovirus mechanism;RNA-Directed DNA Polymerase;Retroviridae;Embryo;Cell Line;Thymine Nucleotides;Mice;Virus Replication;Microscopy, Electron;Clone Cells;15 ERVs retroelements;Cell Transformation, Neoplastic;Oncogenic Viruses}, Medline = {73061740}, Month = {11}, Nlm_Id = {0410463}, Number = {100}, Pages = {157-60}, Pubmed = {4118366}, Title = {Spontaneous release of type C viruses from clonal lines of spontaneously transformed Blab-3T3 cells}, Uuid = {8DFF9FC6-4328-11DB-A5D2-000D9346EC2A}, Volume = {240}, Year = {1972}} @article{Toggas:1994, Abstract = {Many people infected with human immunodeficiency virus type 1 (HIV-1) develop neurological complications that can culminate in dementia and paralysis. The discrepancy between the severity of impairment and the paucity of detectable HIV-1 within neurons has led to an intense search for diffusible virus- and host-derived factors that might be neurotoxic (see ref. 2 for review). The HIV-1 envelope glycoprotein gp120 is an extracellular protein that is shed from infected cells and so has the potential to diffuse and interact with distant uninfected brain cells. Studies on cultured immature cells suggest that gp120 induces neurotoxicity (reviewed in refs 2, 4), and systemic injection of gp120 in neonatal rats and intracerebroventricular injection in adult rats results in deleterious effects on the brain. To assess the pathogenic potential of gp120 in the intact brain, we have now produced gp120 in the brains of transgenic mice and found a spectrum of neuronal and glial changes resembling abnormalities in brains of HIV-1-infected humans. The severity of damage correlated positively with the brain level of gp120 expression. These results provide in vivo evidence that gp120 plays a key part in HIV-1-associated nervous system impairment. This model should facilitate the evaluation and development of therapeutic strategies aimed at HIV-brain interactions.}, Author = {Toggas, S. M. and Masliah, E. and Rockenstein, E. M. and Rall, G. F. and Abraham, C. R. and Mucke, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Research Support, Non-U.S. Gov't;AIDS Dementia Complex;Animals;HIV-1;Astrocytes;Base Sequence;Humans;Brain;Microglia;Mice, Transgenic;Recombinant Fusion Proteins;11 Glia;Research Support, U.S. Gov't, P.H.S.;Neurons;Mice;Molecular Sequence Data;HIV Envelope Protein gp120;Glial Fibrillary Acidic Protein}, Medline = {94159078}, Month = {1}, Nlm_Id = {0410462}, Number = {6459}, Organization = {Department of Neuropharmacology, Scripps Research Institute, La Jolla, California 92037.}, Pages = {188-93}, Pubmed = {8114918}, Title = {Central nervous system damage produced by expression of the HIV-1 coat protein gp120 in transgenic mice}, Uuid = {3BAC6409-FCA9-4A2D-A6F1-7B3CADDE6FE7}, Volume = {367}, Year = {1994}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/367188a0}} @article{Toida:1998, Abstract = {The present study analyzed three-dimensional structural features and synaptic contacts of morphologically and chemically identified calbindin D28K-immunoreactive neurons in the glomerular layer of the rat main olfactory bulb by means of combined confocal laser scanning light microscopy, high-voltage electron microscopy and electron microscopic serial section/three-dimensional reconstruction. Most of calbindin D28K-immunoreactive neurons were identified as the periglomerular cell type by combined high-voltage electron microscopic and confocal laser scanning light microscopic observations, and the minority were the short-axon cell type and others. The combined confocal laser scanning light microscopic and electron microscopic study revealed that the calbindin D28K-immunoreactive neurons exhibited unique synaptic contact patterns; they received asymmetrical synapses from presumed mitral/tufted dendrites and made conversely symmetrical synapses with them. About 30\%of asymmetrical postsynaptic sites and about 40\%of symmetrical presynaptic sites formed reciprocal pairs of synapses. Calbindin D28K-immunoreactive dendrites and somata also received synapses from GABA-like-immunoreactive profiles containing numerous pleomorphic, and a few dense-cored, vesicles. On the other hand, surprisingly, calbindin D28K-immunoreactive neurons had almost no synaptic contacts from olfactory nerve terminals. The present study clearly revealed that calbindin D28K-immunoreactive neurons are a type of periglomerular cell involving unique synaptic contacts that have not been reported so far, and thus indicated that so-called periglomerular cells should be heterogeneous in their synaptic connections as well as in their chemical and structural features.}, Author = {Toida, K. and Kosaka, K. and Heizmann, C. W. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Journal = {J Comp Neurol}, Keywords = {I;Calcium-Binding Protein, Vitamin D-Dependent/*analysis;Rats;Microscopy, Electron;Immunohistochemistry;Neurons/classification/*cytology/ultrastructure;Rats, Wistar;Animal;Nerve Tissue Proteins/*analysis;Olfactory Bulb/*cytology;Support, Non-U.S. Gov't;Models, Structural;GABA/analysis;Synapses/physiology/*ultrastructure;13 Olfactory bulb anatomy}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Kyushu University Faculty of Medicine, Higashiku, Fukuoka, Japan. toida\@a3rd.med.kyushu-u.ac.jp}, Pages = {179-98.}, Title = {Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb: III. Structural features of calbindin D28K-immunoreactive neurons}, Uuid = {C19AA732-2AED-40E9-BA81-1AD1F1A823CC}, Volume = {392}, Year = {1998}, url = {papers/Toida_JCompNeurol1998.pdf}} @article{Toida:1996, Abstract = {Neurons containing a calcium-binding protein parvalbumin in the external plexiform layer of the rat olfactory bulb were identified light microscopically with the pre-embedding immunocytochemistry and were subsequently analysed with the electron microscopic serial- sectioning and three-dimensional reconstructions. In the present study we chose several different types of parvalbumin-immunoreactive neurons identified light microscopically as Van Gehuchten cell type, superficial short-axon cell type and multipolar cell type. Parvalbumin- immunoreactive somata were similar to one another in their ultrastructural characteristics, showing nuclear indentations, moderately developed Golgi apparatus and abundant mitochondria; these structural features appeared to resemble those of the short axon cells around the glomeruli and in the granule cell layer reported in previous electron microscopic studies. All neurons analysed in the present study made symmetrical synapses on to dendrites and somata of presumed mitral/tufted cells and received asymmetrical synapses from them, and occasionally formed reciprocal synapses with them. On the parvalbumin- immunoreactive processes, the asymmetrical synapses nearly equalled the symmetrical ones in number and about 30-50\%of them were identified as reciprocal pairs. In contrast, no presynaptic sites were observed on parvalbumin-immunoreactive somata, and thick portions (more than approximately 2 microns in diameter) of the proximal dendrites, where they were occasionally postsynaptic in some asymmetrical and symmetrical synapses from parvalbumin-immunonegative profiles. Characteristically, parvalbumin-immunoreactive process frequently make direct contacts with one another; processes regarded light microscopically as arising from a soma or a dendrite or parvalbumin- immunoreactive neurons were sometimes revealed to be separate but directly contacting processes with electron microscopic examinations. Although puncta adherentia were occasionally observed between these contact sites, so far neither gap junctions nor chemical synapses were observed. Until now, it has been believed that in the external plexiform layer only granule cells form reciprocal synapses with mitral/tufted cells. However, the present study clearly demonstrates that interneurons different from granule cells, namely GABAergic neurons containing a calcium-binding protein parvalbumin, also make reciprocal synapses with mitral/tufted cells in the external plexiform layer. Therefore, neuronal processes making reciprocal synapses with mitral/tufted cells in the external plexiform layer cannot be determined a priori as granule cell processes.}, Author = {Toida, K. and Kosaka, K. and Heizmann, C. W. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Neuroscience}, Keywords = {I;Interneurons/metabolism/ultrastructure;Image Processing, Computer-Assisted;Immunohistochemistry;Microscopy, Electron;Rats;Parvalbumins/*metabolism;Rats, Wistar;Animal;Olfactory Bulb/*metabolism/*ultrastructure;Support, Non-U.S. Gov't;Mitochondria/metabolism/ultrastructure;Neurons/*metabolism/*ultrastructure;Male;13 Olfactory bulb anatomy}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.}, Pages = {449-66.}, Title = {Electron microscopic serial-sectioning/reconstruction study of parvalbumin-containing neurons in the external plexiform layer of the rat olfactory bulb}, Uuid = {36346847-0E50-490A-B29C-E5D61E89A9C5}, Volume = {72}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8737415}} @article{Toida:2000, Abstract = {Synapses of intraglomerular processes of tyrosine hydroxylase- immunoreactive neurons in the rat main olfactory bulb were examined by electron microscopic immunocytochemistry. Prominent characteristics of intraglomerular synapses of tyrosine hydroxylase-immunoreactive elements were that the vast majority (about 80\%) of their synaptic inputs were asymmetrical synapses from olfactory nerve terminals and, though far smaller in proportion, one half of the remaining were asymmetrical synapses from mitral/tufted cell dendrites and the other half were symmetrical synapses from gamma-aminobutyric acid-like immunoreactive elements. So far, we have observed no typical reciprocal synapses between tyrosine hydroxylase-immunoreactive processes and mitral/tufted dendrites; however, we have often identified serial synapses; that is, asymmetrical synapses from olfactory nerve terminals or mitral/tufted cell dendrites to tyrosine hydroxylase-immunoreactive processes, and then symmetrical synapses from the latter to different mitral/tufted cell dendrites. These synaptic connections of tyrosine hydroxylase-immunoreactive neurons were very different from those of Calbindin-D(28k)-immunoreactive neurons, which received no synaptic contact directly from olfactory nerve terminals but formed reciprocal synapses with mitral/tufted cells as we analysed previously.Thus, our present and previous electron microscopic studies combined with confocal laser scanning light microscopy clearly indicated for the first time the heterogeneity of periglomerular neurons, not only in their chemical and morphological features, but also in their synaptic organization in the olfactory glomerulus. Using Smart Source Parsing}, Author = {Toida, K. and Kosaka, K. and Aika, Y. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Neuroscience}, Keywords = {I;Olfactory Bulb/*metabolism/ultrastructure;Olfactory Nerve/metabolism/ultrastructure;Tyrosine 3-Monooxygenase/*metabolism;Smell/physiology;Rats;Cell Size/physiology;Neural Pathways/*metabolism/ultrastructure;Neurons/*metabolism/ultrastructure;Rats, Wistar;Animal;Support, Non-U.S. Gov't;Male;13 Olfactory bulb anatomy;Dendrites/metabolism/ultrastructure;Synapses/*metabolism/ultrastructure}, Number = {1}, Organization = {Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka, 812-8582, Japan. toida\@basic.med.tokushima-u.ac.jp}, Pages = {11-7}, Title = {Chemically defined neuron groups and their subpopulations in the glomerular layer of the rat main olfactory bulb--IV. Intraglomerular synapses of tyrosine hydroxylase-immunoreactive neurons}, Uuid = {88DF0CD8-AB61-4569-9B31-2C214F3A6FA8}, Volume = {101}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11068132}} @article{Toledo-Rodriguez:2004, Abstract = {The computational power of the neocortex arises from interactions of multiple neurons, which display a wide range of electrical properties. The gene expression profiles underlying this phenotypic diversity are unknown. To explore this relationship, we combined whole-cell electrical recordings with single-cell multiplex RT-PCR of rat (p13-16) neocortical neurons to obtain cDNA libraries of 26 ion channels (including voltage activated potassium channels, Kv1.1/2/4/6, Kvbeta1/2, Kv2.1/2, Kv3.1/2/3/4, Kv4.2/3; sodium/potassium permeable hyperpolarization activated channels, HCN1/2/3/4; the calcium activated potassium channel, SK2; voltage activated calcium channels, Caalpha1A/B/G/I, Cabeta1/3/4), three calcium binding proteins (calbindin, parvalbumin and calretinin) and GAPDH. We found a previously unreported clustering of ion channel genes around the three calcium-binding proteins. We further determined that cells similar in their expression patterns were also similar in their electrical properties. Subsequent regression modeling with statistical resampling yielded a set of coefficients that reliably predicted electrical properties from the expression profile of individual neurons. This is the first report of a consistent relationship between the co-expression of a large profile of ion channel and calcium binding protein genes and the electrical phenotype of individual neocortical neurons.}, Author = {Toledo-Rodriguez, Maria and Blumenfeld, Barak and Wu, Caizhi and Luo, Junyi and Attali, Bernard and Goodman, Philip and Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Research Support, Non-U.S. Gov't;21 Neurophysiology;Action Potentials;Predictive Value of Tests;Rats;Neocortex;Gene Expression Profiling;Rats, Wistar;In Vitro;Animals;24 Pubmed search results 2008;Neurons}, Month = {12}, Nlm_Id = {9110718}, Number = {12}, Organization = {Brain and Mind Institute, EPFL, Lausanne 1015, Switzerland.}, Pages = {1310-27}, Pii = {bhh092}, Pubmed = {15192011}, Title = {Correlation maps allow neuronal electrical properties to be predicted from single-cell gene expression profiles in rat neocortex}, Uuid = {092E318D-B8C4-4FEF-B946-D1C205B783FD}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh092}} @article{Tomita:2004, Abstract = {Choroidal neovascularization (CNV) is a known cause of age-related macular degeneration (ARMD). Moreover, the most common cause of blindness in the elderly in advanced countries is ARMD with CNV. It has recently been shown that bone marrow cells (BMCs) can differentiate into various cell lineages in vitro and in vivo. Adults maintain a reservoir of hematopoietic stem cells included in BMCs that can enter the circulation to reach various organs in need of regeneration. It has recently been reported that endothelial progenitor cells (EPCs) included in BMCs are associated with neovascularization. We examine the role of BMCs in CNV using a model of CNV in adult mice. Using methods consisting of fractionated irradiation (6.0 Gy x 2) followed by bone marrow transplantation (BMT), adult mice were engrafted with whole BMCs isolated from transgenic mice expressing enhanced green fluorescent protein (EGFP). Three months after BMT, we confirmed that the hematopoietic cells in the recipients had been completely replaced with donor cells. We then carried out laser photocoagulation to induce CNV in chimeric mice (donor cells >95\%). Two weeks after the laser photocoagulation, by which time CNV had occurred, immunohistochemical examination was carried out. The vascular wall cells of the CNV expressed both EGFP and CD31. These findings indicate that newly developed blood vessels in the CNV are derived from the BMCs and suggest that the inhibition of EPC mobilization from the bone marrow to the eyes could be a new approach to the fundamental treatment of CNV in ARMD.}, Author = {Tomita, Minoru and Yamada, Haruhiko and Adachi, Yasushi and Cui, Yunze and Yamada, Eri and Higuchi, Akiko and Minamino, Keizo and Suzuki, Yasuhiko and Matsumura, Miyo and Ikehara, Susumu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {Cell Differentiation;Animals;Macular Degeneration;Endothelial Cells;Choroidal Neovascularization;Mice, Transgenic;Cell Movement;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Disease Models, Animal;Hematopoietic Stem Cell Transplantation;Antigens, CD31;Radiation Chimera;Male;Cell Lineage;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Graft Survival;Light Coagulation;Blood Vessels}, Nlm_Id = {9304532}, Number = {1}, Organization = {First Department of Pathology, Kansai Medical University, Moriguchi City, Osaka, Japan.}, Pages = {21-6}, Pubmed = {14688388}, Title = {Choroidal neovascularization is provided by bone marrow cells}, Uuid = {48E22B41-9141-4206-BFD2-B4A5D2D61E36}, Volume = {22}, Year = {2004}} @article{Tomita:2006, Abstract = {Retinal progenitor cells (RPCs) are immature precursors that can differentiate into retinal neurons, including photoreceptors. Recently, it has been reported that bone marrow-derived cells may also be capable of differentiation into cells of central nervous system lineage, including retinal neurons. We compared these two cell types to evaluate their potential as a source of cells for retinal transplantation. Marrow stromal cells (MSCs) and macrophages were isolated from enhanced green fluorescence protein mice. MSCs were cultured with brain-derived neurotrophic factor, nerve growth factor, and basic fibroblast growth factor to induce neuronal differentiation. RPCs were cultured under the same conditions or with 10\%fetal bovine serum. Neuronal marker expression was examined and compared between MSCs and RPCs. MSCs, macrophages, and RPCs were also cultured with explanted retinas from rhodopsin knockout mice to study their potential for retinal integration. MSCs expressed neuronal and retina-specific markers by reverse transcription-polymerase chain reaction and immunocytochemistry. Both types of cells migrated into retinal explants and expressed neurofilament 200, glial fibrillary acidic protein, protein kinase C-alpha, and recoverin. RPCs expressed rhodopsin, a photoreceptor marker we never detected in MSCs. A majority of bone marrow derived-macrophages differentiated into cells that resembled microglia, rather than neural cells, in the explanted retina. This study shows that RPCs are likely to be a preferred cell type for retinal transplantation studies, compared with MSCs. However, MSCs may remain an attractive candidate for autologous transplantation.}, Author = {Tomita, Minoru and Mori, Taisuke and Maruyama, Kazuichi and Zahir, Tasneem and Ward, Matthew and Umezawa, Akihiro and Young, Michael J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {Retina;Cell Differentiation;Cell Culture Techniques;Animals;Cells, Cultured;Macrophages;comparative study;Stem Cell Transplantation;Rhodopsin;Microglia;Cell Movement;Mice, Inbred C57BL;research support, non-u.s. gov't;Bone Marrow Cells;Mice, Knockout;Neurons;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Stem Cells;Stromal Cells;research support, u.s. gov't, non-p.h.s.}, Month = {10}, Nlm_Id = {9304532}, Number = {10}, Organization = {The Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, 20 Staniford St., Boston, Massachusetts 02114, USA. tomita\@vision.eri.harvard.edu}, Pages = {2270-8}, Pii = {24/10/2270}, Pubmed = {17008430}, Title = {A comparison of neural differentiation and retinal transplantation with bone marrow-derived cells and retinal progenitor cells}, Uuid = {91D0229C-51AC-4588-A1EF-4A41621925F1}, Volume = {24}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1634/stemcells.2005-0507}} @article{Tonchev:2003a, Abstract = {We investigated the fate of proliferating cells in the adult monkey brain after global ischemia. We used the thymidine analogue bromodeoxyuridine (BrdU) to label S-phase cells and their progeny in Japanese macaques subjected to global cerebral ischemia for 20 min or to a sham operation. Subsequently, newly generated cells were identified by BrdU immunohistochemistry, and their immunophenotype was determined quantitatively, using specific markers. The ischemic insult significantly increased the number of proliferating cells in the hippocampus and temporal neocortex, where the majority BrdU-labeled cells expressed markers for microglia (Iba1, CD68, and Ham56) or astrocytes (S-100beta and glial fibrillary acidic protein [GFAP]). In contrast, the proliferation level in the parahippocampal region remained unchanged. This discrepancy prompted us to investigate the postischemic response in the olfactory bulb, a well-known site of adult cell generation that is anatomically distant from the above-mentioned regions but that is also subjected to the global ischemic insult. The olfactory bulb contained clusters of proliferating cells expressing markers for neural (Musashi1 and Nestin) and/or neuronal (class III beta-tubulin) progenitors; these were immunophenotypically distinct from other cell types. Their number and distribution were unaltered by ischemia. Our results demonstrate that cell proliferation and differentiation in the adult macaque brain and olfactory bulb are differentially affected by a common insult.}, Author = {Tonchev, Anton B. and Yamashima, Tetsumori and Zhao, Liang and Okano, Hideyuki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Glial Fibrillary Acidic Protein;Research Support, Non-U.S. Gov't;Cell Differentiation;Animals;Astrocytes;Biological Markers;Comparative Study;Tubulin;Microglia;Female;Macaca;RNA-Binding Proteins;Nerve Regeneration;Olfactory Bulb;Antigens, CD56;Antibodies, Monoclonal;Calcium-Binding Proteins;Cerebral Cortex;Neurons;Intermediate Filament Proteins;Gliosis;Brain Ischemia;Cell Division;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine;Stem Cells;Nerve Tissue Proteins;S100 Proteins}, Medline = {22560378}, Month = {5}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Neurosurgery, Kanazawa University Graduate School of Medical Science, Kanazawa City, Japan.}, Pages = {209-24}, Pubmed = {12673828}, Title = {Differential proliferative response in the postischemic hippocampus, temporal cortex, and olfactory bulb of young adult macaque monkeys}, Uuid = {FE5A75A6-5FDA-4A8E-A339-3749732D16C5}, Volume = {42}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10209}} @article{Tonchev:2003, Abstract = {To investigate the effect of global cerebral ischemia on brain cell proliferation in young adult macaques, we infused 5-bromo-2'-deoxyuridine (BrdU), a DNA replication indicator, into monkeys subjected to ischemia or sham-operated. Subsequent quantification by BrdU immunohistochemistry revealed a significant postischemic increase in the number of BrdU-labeled cells in the hippocampal dentate gyrus, subventricular zone of the temporal horn of the lateral ventricle, and temporal neocortex. In all animals, 20-40\%of the newly generated cells in the dentate gyrus and subventricular zone expressed the neural progenitor cell markers Musashi1 or Nestin. A few BrdU-positive cells in postischemic monkeys were double-stained for markers of neuronal progenitors (class III beta-tubulin, TUC4, doublecortin, or Hu), neurons (NeuN), or glia (S100beta or GFAP). Our results suggest that ischemia activates endogenous neuronal and glial precursors residing in diverse locations of the adult primate central nervous system. 1044-7431 Journal Article}, Author = {Tonchev, A. B. and Yamashima, T. and Zhao, L. and Okano, H. J. and Okano, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:33 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {Neuronal Plasticity/*physiology;Support, Non-U.S. Gov't;Dentate Gyrus;06 Adult neurogenesis injury induced;Research Support, Non-U.S. Gov't;24 Pubmed search results 2008;Immunohistochemistry;Dentate Gyrus/cytology/growth &development/metabolism;Nerve Regeneration;Bromodeoxyuridine/diagnostic use;Brain Ischemia;Animals;Telencephalon/cytology/*growth &development/metabolism;RNA-Binding Proteins/metabolism;Cell Division/physiology;Phenotype;Bromodeoxyuridine;Intermediate Filament Proteins;RNA-Binding Proteins;Cell Division;Lateral Ventricles;Nerve Regeneration/*physiology;Neuronal Plasticity;Biological Markers;Cell Death/physiology;DNA Damage/physiology;Macaca;D pdf;Cell Death;Neurons/cytology/*metabolism;Female;Telencephalon;Stem Cells/cytology/*metabolism;DNA Damage;Temporal Lobe;Lateral Ventricles/cytology/growth &development/metabolism;Stem Cells;Nerve Tissue Proteins/metabolism;Neurons;Brain Ischemia/*metabolism/physiopathology;Nerve Tissue Proteins;Temporal Lobe/cytology/growth &development/metabolism;Intermediate Filament Proteins/metabolism}, Medline = {22697603}, Month = {6}, Nlm_Id = {9100095}, Number = {2}, Organization = {Department of Neurosurgery, Division of Neuroscience, Kanazawa University Graduate School of Medical Science, Kanazawa, 920-8641, Japan.}, Pages = {292-301}, Pii = {S1044743103000587}, Pubmed = {12812760}, Title = {Proliferation of neural and neuronal progenitors after global brain ischemia in young adult macaque monkeys}, Uuid = {530E602F-EC81-11DA-8605-000D9346EC2A}, Volume = {23}, Year = {2003}, url = {papers/Tonchev_MolCellNeurosci2003}} @article{Torii:2005, Abstract = {Molecular mechanisms generating the topographic organization of corticothalamic (CT) circuits, which comprise more than three-quarters of the synaptic inputs onto sensory relay neurons, and their interdependence with thalamocortical (TC) axon development are unknown. Using in utero electroporation-mediated gene transfer, we show that EphA7-mediated signaling on neocortical axons controls the within-nucleus topography of CT projections in the thalamus. Notably, CT axons that mis-express EphA7 do not shift the relative positioning of their pathway within the subcortical telencephalon (ST), indicating that they do not depend upon EphA7/ephrin-A signaling in the ST for establishing this topography. Moreover, mis-expression of cortical EphA7 results in disrupted topography of CT projections, but unchanged inter- and intra-areal topography of TC projections. Our results support a model in which EphA/ephrin-A signaling controls independently the precision with which CT and TC projections develop, yet is essential for establishing their topographic reciprocity.}, Author = {Torii, Masaaki and Levitt, Pat}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Thalamus;Receptor, EphA7;24 Pubmed search results 2008;10 Development;Telencephalon;Neural Pathways;10 circuit formation;Neocortex;Receptor, EphA5;research support, n.i.h., extramural;Brain Mapping;Synaptic Transmission;Animals;Mice;Cerebral Cortex;Mice, Inbred Strains;Axons}, Month = {11}, Nlm_Id = {8809320}, Number = {4}, Organization = {Vanderbilt Kennedy Center for Research on Human Development and Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37203, USA.}, Pages = {563-75}, Pii = {S0896-6273(05)00788-9}, Pubmed = {16301174}, Title = {Dissociation of corticothalamic and thalamocortical axon targeting by an EphA7-mediated mechanism}, Uuid = {CA8E51B1-58BF-4FF2-BAF2-71D442BF7559}, Volume = {48}, Year = {2005}, url = {papers/Torii_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.09.021}} @article{Torres-Reveron:2007, Abstract = {Subplate (SP) neurons are important for the proper development of thalamocortical innervation. They are necessary for formation of ocular dominance and orientation columns in visual cortex. During the perinatal period, many SP neurons die. The surviving cohort forms interstitial cells in the white matter (WM) and a band of horizontally oriented cells below layer VI (layer VIb, layer VII, or subplate cells). Although the function of embryonic SP neurons has been well established, the functional roles of WM and postnatal SP cells are not known. We used a combination of anatomical, immunohistochemical, and electrophysiological techniques to explore the dendritic morphology, neurotransmitter phenotype, intrinsic electrophysiological, and synaptic input properties of these surviving cells in the rat visual cortex. The density of SP and WM cells significantly decreases during the first month of life. Both populations express neuronal markers and have extensive dendritic arborizations within the SP, WM, and to the overlying visual cortex. Some intrinsic electrophysiological properties of SP and WM cells are similar: each generates high-frequency slowly adapting trains of action potentials in response to a sustained depolarization. However, SP cells exhibit greater frequency-dependent action potential broadening than WM neurons. Both cell types receive predominantly AMPA/kainate receptor-mediated excitatory synaptic input that undergoes paired-pulse facilitation as well as NMDA receptor and GABAergic input. Synaptic inputs to these cells can also undergo long-term synaptic plasticity. Thus, surviving SP and WM cells are functional electrogenic neurons integrated within the postnatal visual cortical circuit.}, Author = {Torres-Reveron, Juan and Friedlander, Michael J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Visual Cortex;Rats, Sprague-Dawley;21 Neurophysiology;Action Potentials;Neuronal Plasticity;Rats;Cell Survival;comparative study;research support, n.i.h., extramural;Animals, Newborn;Animals;Nerve Fibers, Myelinated;Visual Pathways;Neurons;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8102140}, Number = {37}, Organization = {Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.}, Pages = {9962-74}, Pii = {27/37/9962}, Pubmed = {17855610}, Title = {Properties of persistent postnatal cortical subplate neurons}, Uuid = {6094A116-956F-4A06-B53B-E8B2BCFEB106}, Volume = {27}, Year = {2007}, url = {papers/Torres-Reveron_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1536-07.2007}} @article{Touret:2007, Abstract = {BACKGROUND: In absence epilepsy, the neuronal hyper-excitation and hyper-synchronization, which induce spike and wave discharges in a cortico-thalamic loop are suspected to be due to an imbalance between GABA and glutamate (GLU) neurotransmission. In order to elucidate the role played by GLU in disease outcome, we measured cortical and thalamic extracellular levels of GLU and GABA. We used an in vivo quantitative microdialysis approach (no-net-flux method) in an animal model of absence epilepsy (GAERS). In addition, by infusing labelled glutamate through the microdialysis probe, we studied in vivo glutamate uptake in the cortex and thalamus in GAERS and non-epileptic control (NEC) rats. Expression of the vesicular glutamate transporters VGLUT1 and VGLUT2 and a synaptic component, synaptophysin, was also measured. RESULTS: Although extracellular concentrations of GABA and GLU in the cortex and thalamus were not significantly different between GAERS and NEC rats, cortical GLU uptake was significantly decreased in unrestrained awake GAERS. Expression of VGLUT2 and synaptophysin was increased in the cortex of GAERS compared to NEC rats, but no changes were observed in the thalamus. CONCLUSION: The specific decrease in GLU uptake in the cortex of GAERS linked to synaptic changes suggests impairment of the glutamatergic terminal network. These data support the idea that a change in glutamatergic neurotransmission in the cortex could contribute to hyperexcitability in absence epilepsy.}, Author = {Touret, Monique and Parrot, Sandrine and Denoroy, Luc and Belin, Marie-Fran\c{c}oise F. and Didier-Bazes, Marianne}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1471-2202}, Journal = {BMC Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;24 Pubmed search results 2008;21 Epilepsy}, Nlm_Id = {100966986}, Organization = {INSERM, U842, Lyon; Universit{\'e} de Lyon, Lyon1, Facult{\'e} de M{\'e}decine Laennec, UMR-S842, Lyon, F-69372, France. touret\@univ-lyon1.fr}, Pages = {69}, Pii = {1471-2202-8-69}, Pubmed = {17725845}, Title = {Glutamatergic alterations in the cortex of genetic absence epilepsy rats}, Uuid = {B1AF8D45-3DED-4A97-9FF0-6C3ABE97FD71}, Volume = {8}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1471-2202-8-69}} @article{Toyo-oka:2003, Abstract = {Heterozygous deletions of 17p13.3 result in the human neuronal migration disorders isolated lissencephaly sequence (ILS) and the more severe Miller-Dieker syndrome (MDS). Mutations in PAFAH1B1 (the gene encoding LIS1) are responsible for ILS and contribute to MDS, but the genetic causes of the greater severity of MDS are unknown. Here, we show that the gene encoding 14-3-3epsilon (YWHAE), one of a family of ubiquitous phosphoserine/threonine-binding proteins, is always deleted in individuals with MDS. Mice deficient in Ywhae have defects in brain development and neuronal migration, similar to defects observed in mice heterozygous with respect to Pafah1b1. Mice heterozygous with respect to both genes have more severe migration defects than single heterozygotes. 14-3-3epsilon binds to CDK5/p35-phosphorylated NUDEL and this binding maintains NUDEL phosphorylation. Similar to LIS1, deficiency of 14-3-3epsilon results in mislocalization of NUDEL and LIS1, consistent with reduction of cytoplasmic dynein function. These results establish a crucial role for 14-3-3epsilon in neuronal development by sustaining the effects of CDK5 phosphorylation and provide a molecular explanation for the differences in severity of human neuronal migration defects with 17p13.3 deletions.}, Author = {Toyo-oka, Kazuhito and Shionoya, Aki and Gambello, Michael J. and Cardoso, Carlos and Leventer, Richard and Ward, Heather L. and Ayala, Ramses and Tsai, Li-Huei H. and Dobyns, William and Ledbetter, David and Hirotsune, Shinji and Wynshaw-Boris, Anthony}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Dynein ATPase;Immunoenzyme Techniques;24 Pubmed search results 2008;Green Fluorescent Proteins;Phosphoprotein Phosphatases;Male;Brain Diseases;Cyclin-Dependent Kinases;Luminescent Proteins;10 Development;Animals;Cell Cycle Proteins;Cells, Cultured;Protein Kinase C;Brain;Coatomer Protein;Cell Movement;1-Alkyl-2-acetylglycerophosphocholine Esterase;Mice, Inbred C57BL;research support, u.s. gov't, p.h.s.;Microtubule-Associated Proteins;Abnormalities, Multiple;14-3-3 Proteins;Enzyme Inhibitors;Female;Syndrome;research support, non-u.s. gov't;Mice;Neurons;Humans;Tyrosine 3-Monooxygenase;10 genetics malformation;Cyclin-Dependent Kinase 5}, Month = {7}, Nlm_Id = {9216904}, Number = {3}, Organization = {Department of Pediatrics, UCSD Cancer Center, University of California, San Diego School of Medicine, 9500 Gilman Drive, Mailstop 0627, La Jolla, California 92093-0627, USA.}, Pages = {274-85}, Pii = {ng1169}, Pubmed = {12796778}, Title = {14-3-3epsilon is important for neuronal migration by binding to NUDEL: a molecular explanation for Miller-Dieker syndrome}, Uuid = {71E48F49-21C4-47E9-845C-8DDB07B7CD54}, Volume = {34}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ng1169}} @article{Tornquist:1997, Abstract = {Motor nerve transection in adult rats induce a series of metabolic and structural changes in the injured neurons as well as in surrounding glial cells; however, without substantial neuronal degeneration. In the present study we found, in contrast with axotomy, a massive neuronal death in the ipsilateral hypoglossal nucleus following injection of toxic ricin (RCA) into the hypoglossal nerve, which is in line with previous observations. Injection of RCA enables examination of the glial reaction in a situation where neuronal degeneration is profound, which has been the approach in the present study. We found an increase in OX42-, GFAP-, and transferrin-immunoreactivity in microglial, astroglial, and oligodendroglial cells respectively, in the ipsilateral hypoglossal nucleus three to seven days following injection of toxic ricin in the hypoglossal nerve. Proliferation was found in astrocytes as well as in microglial cells, as shown by uptake of bromodeoxyuridine. In addition, the complement cascade was activated locally in the ipsilateral hypoglossal nucleus, as demonstrated by immunohistochemical detection of complement components C3d and C9. Complement activation may serve several effects in the glial-neuronal interactions. Stimulation of phagocytosis by reactive microglia is probably the most important one. Furthermore, the degenerative neuronal somata showed increased immunoreactivity for clusterin, which is a known complement inhibitor, but a decrease in clusterin-mRNA. In conclusion, the glial cell response was in several aspects principally different following massive motorneuron degeneration induced by toxic ricin in comparison to previous findings reported after axotomy.}, Author = {T{\"o}rnquist, E. and Liu, L. and Mattsson, P. and Svensson, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Glycoproteins;Median Eminence;Nerve Degeneration;Animals;Ricin;Rats;Female;Complement Inactivators;Rats, Sprague-Dawley;Not relevant;11 Glia;In Situ Hybridization;Support, Non-U.S. Gov't;Neuroglia;Molecular Chaperones;Complement Activation;Motor Neurons;Immunohistochemistry;Injections;Cell Death;Hypoglossal Nerve}, Medline = {97364195}, Month = {6}, Nlm_Id = {8500749}, Number = {2}, Organization = {Department of Neuroscience, Karolinska Institute, Stockholm, Sweden.}, Pages = {167-75}, Pii = {S0168010297000400}, Pubmed = {9220473}, Title = {Response of glial cells and activation of complement following motorneuron degeneration induced by toxic ricin}, Uuid = {1C9E6BBC-F740-4D4E-94E2-4682CCE066ED}, Volume = {28}, Year = {1997}} @article{Tramontin:2003, Abstract = {The germinal neuroepithelium, or ventricular zone (VZ) of the developing fetal brain, was once thought to transform into the non-germinal ependymal zone of the postnatal and adult brain. Persistence of neural stem cells and neurogenesis throughout postnatal life, however, suggests a continuum between embryonic and adult germinal brain centers. Here, we suggest that developmental changes in anatomy and molecular marker expression in the ventricular walls (the principal germinal centers of the brain) may have misled us into current interpretations of VZ transformation from a germinal to a non-germinal epithelium. We review previous studies and present new data indicating that a germinal layer with characteristics similar to those of the embryonic VZ persists in lateral ventricular walls of the postnatal mouse brain, a region where the adult subventricular zone (SVZ) develops and where neurogenesis persists into adult life. The early postnatal VZ is largely composed of radial glial cell bodies that remain proliferative, display interkinetic nuclear migration and serve as progenitors of new neurons. Ependymal cells then progressively populate the walls of the lateral ventricle but a subpopulation of astrocytes, derived from radial glia, remain in contact with the ventricle lumen, into which they extend a single cilium similar to that found on neuroepithelial cells and radial cells. We propose that a VZ 'compartment'is retained postnatally and that this niche may be essential for stem cell function. 1047-3211 Journal Article Review Review, Tutorial}, Author = {Tramontin, A. D. and Garcia-Verdugo, J. M. and Lim, D. A. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {Cereb Cortex}, Keywords = {01 Adult neurogenesis general;Neuroglia/*cytology/*physiology;Stem Cells/*cytology/physiology;Cerebral Ventricles/*cytology/embryology/*growth &development/physiology;Cell Differentiation/physiology;Animals, Newborn;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;Mice;A pdf;Neurons/cytology/physiology}, Number = {6}, Organization = {Department of Neurosurgery Research, University of California, San Francisco, CA 94143, USA. tonyt\@itsa.ucsf.edu}, Pages = {580-7}, Pubmed = {12764031}, Title = {Postnatal development of radial glia and the ventricular zone (VZ): a continuum of the neural stem cell compartment}, Uuid = {0DFAE8E1-06EC-47B7-AA0C-448A4150BA75}, Volume = {13}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12764031}} @article{Tran:2007, Abstract = {We previously demonstrated that chemokine receptors are expressed by neural progenitors grown as cultured neurospheres. To examine the significance of these findings for neural progenitor function in vivo, we investigated whether chemokine receptors were expressed by cells having the characteristics of neural progenitors in neurogenic regions of the postnatal brain. Using in situ hybridization we demonstrated the expression of CCR1, CCR2, CCR5, CXCR3, and CXCR4 chemokine receptors by cells in the dentate gyrus (DG), subventricular zone of the lateral ventricle, and olfactory bulb. The pattern of expression for all of these receptors was similar, including regions where neural progenitors normally reside. In addition, we attempted to colocalize chemokine receptors with markers for neural progenitors. In order to do this we used nestin-EGFP and TLX-LacZ transgenic mice, as well as labeling for Ki67, a marker for dividing cells. In all three areas of the brain we demonstrated colocalization of chemokine receptors with these three markers in populations of cells. Expression of chemokine receptors by neural progenitors was further confirmed using CXCR4-EGFP BAC transgenic mice. Expression of CXCR4 in the DG included cells that expressed nestin and GFAP as well as cells that appeared to be immature granule neurons expressing PSA-NCAM, calretinin, and Prox-1. CXCR4-expressing cells in the DG were found in close proximity to immature granule neurons that expressed the chemokine SDF-1/CXCL12. Cells expressing CXCR4 frequently coexpressed CCR2 receptors. These data support the hypothesis that chemokine receptors are important in regulating the migration of progenitor cells in postnatal brain. J. Comp. Neurol. 500:1007-1033, 2007. (c) 2006 Wiley-Liss, Inc.}, Author = {Tran, Phuong B. and Banisadr, Ghazal and Ren, Dongjun and Chenn, Anjen and Miller, Richard J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0406041}, Number = {6}, Organization = {Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, Chicago, Illinois 60611.}, Pages = {1007-34}, Pubmed = {17183554}, Title = {Chemokine receptor expression by neural progenitor cells in neurogenic regions of mouse brain}, Uuid = {43EE2C8B-6E66-4C7A-BE20-ABDC81390E7C}, Volume = {500}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21229}} @article{Tran:1998, Abstract = {There is increasing evidence that microglia serve as antigen presenters in the human CNS. Although the occurrence of MHC class II immunoreactive cells has been reported in astrocytic gliomas, the relative contribution of microglia to this cell population has not been studied in detail. Using computer-assisted image analysis, we have investigated the expression of MHC class II molecules and of the microglia/macrophage markers Ki-MIP, RCA-1, KP1 and iba1, in 97 astrocytic gliomas comprising all WHO grades to answer the question whether there is a correlation between tumour grade and the number of MHC class II positive microglia/macrophage profiles. Microglia expressing MHC class II were common in astrocytomas and anaplastic astrocytomas but rare in pilocytic tumours although there was significant variation within each group. MHC class II immunoreactivity was reduced in highly cellular areas of glioblastomas where large numbers of cells expressing macrophage markers were still present. Thus, there was no simple relationship between tumour grade and microglial/macrophage MHC class II expression. In addition, up to 55\%of astrocytic gliomas contained MHC class II immunoreactive tumour cells. Microglia but not tumour cells were found to express the BB1/B7 costimulator. We conclude that microglia in astrocytic gliomas are well equipped to function as antigen presenting cells. Yet, neoplastic astroglia appear to acquire the capacity to downregulate microglial MHC class II expression and, at the same time, may induce T-cell clonal anergy through aberrant expression of MHC class II molecules.}, Author = {Tran, C. T. and Wolz, P. and Egensperger, R. and K{\"o}sel, S. and Imai, Y. and Bise, K. and Kohsaka, S. and Mehraein, P. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0305-1846}, Journal = {Neuropathol Appl Neurobiol}, Keywords = {Immunotherapy;Paraffin Embedding;Glioblastoma;Research Support, Non-U.S. Gov't;Antigen Presentation;Histocompatibility Antigens Class II;Astrocytes;T-Lymphocytes;11 Glia;Gene Expression Regulation, Neoplastic;Macrophages;Humans;Biopsy}, Medline = {98448521}, Month = {8}, Nlm_Id = {7609829}, Number = {4}, Organization = {Institute of Neuropathology, Ludwig-Maximilians-University, Munich, Germany.}, Pages = {293-301}, Pubmed = {9775395}, Title = {Differential expression of MHC class II molecules by microglia and neoplastic astroglia: relevance for the escape of astrocytoma cells from immune surveillance}, Uuid = {C81D2502-B197-4FFE-880C-376E7B412F21}, Volume = {24}, Year = {1998}} @article{Trapp:2006, Abstract = {Recent studies have described significant demyelination and microglial activation in the cerebral cortex of brains from multiple sclerosis patients. To date, however, experimental models of cortical demyelination or cortical inflammation have not been extensively studied. In this report we describe focal cortical inflammation induced by stereotaxic injection of killed bacteria (BCG), followed 1 month later by subcutaneous injection of the same antigen, a protocol that overcomes the immune privilege of the cortex. Intracerebral BCG injection produced focal microglial activation at the injection site (termed acute lesion). Ten days after peripheral challenge (termed immune-mediated lesion), larger areas and higher densities of activated microglia were found near the injection site. In both paradigms, activated microglia and/or their processes closely apposed neuronal perikarya and apical dendrites. In the immune-mediated lesions, approximately 45\%of the axosomatic synapses was displaced by activated microglia. Upon activation, therefore, cortical microglial migrate to and strip synapses from neuronal perikarya. Since neuronal pathology was not a feature of either the acute or immune-mediated lesion, synaptic stripping by activated microglia may have neuroprotective consequences. (c) 2006 Wiley-Liss, Inc.}, Author = {Trapp, and Wujek, and Criste, and Jalabi, and Yin, and Kidd, and Stohlman, and Ransohoff,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8806785}, Organization = {Department of Neurosciences, Lerner Research Institute, The Cleveland Clinic, Cleveland, Ohio.}, Pubmed = {17136771}, Title = {Evidence for synaptic stripping by cortical microglia}, Uuid = {318DF3A8-9F94-4C7E-88FD-F43E44F29407}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20462}} @article{Trapp:1997, Abstract = {Previous studies have indicated that newly formed oligodendrocytes are dynamic cells whose production, survival, and differentiation depend upon axonal influences. This study has characterized the appearance and fate of newly formed oligodendrocytes in developing rat brain. Oligodendrocytes appear in predictable locations and radially extend DM-20-positive processes that cover 80-microm domains in the cortex and 40-microm domains in the corpus callosum. These premyelinating oligodendrocytes have one of two fates: they myelinate axons or degenerate. Between 7 and 21 d after birth, approximately 20\%of premyelinating oligodendrocytes identified in the cerebral cortex were degenerating. Oligodendrocytes that ensheathed axons expressed and selectively targeted proteolipid protein to compact myelin and did not degenerate. These observations support the hypothesis that axonal influences affect oligodendrocyte survival, differentiation, and expression of proteolipid protein gene products. 0021-9525 Journal Article}, Author = {Trapp, B. D. and Nishiyama, A. and Cheng, D. and Macklin, W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:00 -0400}, Journal = {J Cell Biol}, Keywords = {Chromatin/chemistry;Cell Differentiation;Rats, Sprague-Dawley;Corpus Callosum/chemistry/cytology;Myelin Proteolipid Protein/*analysis;Rats;Oligodendroglia/*cytology/metabolism;11 Glia;Cell Death;Axons/metabolism;Cerebral Cortex/chemistry/cytology;Animals;Support, Non-U.S. Gov't;G;Brain/*cytology/growth &development;Support, U.S. Gov't, P.H.S.}, Number = {2}, Organization = {Department of Neurosciences, Research Institute, The Cleveland Clinic Foundation, Ohio 44195, USA.}, Pages = {459-68}, Pubmed = {9128255}, Title = {Differentiation and death of premyelinating oligodendrocytes in developing rodent brain}, Uuid = {DE9AF883-2B2A-4DC0-A753-0288235C4E25}, Volume = {137}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9128255}} @article{Traub:2004, Abstract = {A variety of population oscillations, at frequencies approximately 5 Hz up to 200 Hz and above, can be induced in hippocampal slices either by (a) manipulation of the ionic environment, or (b) by stimulation of metabotropic receptors; brief oscillations can even occur spontaneously. In this review, we consider in vitro theta (4-12 Hz), gamma/beta (15-70 Hz), and very fast oscillations (VFO) (>70 Hz). Many in vitro oscillations are gated by synaptic inhibition but are influenced by electrical coupling as well; one type depends solely on electrical coupling. For some oscillations dependent upon inhibition, the detailed firing patterns of interneurons can influence long-range synchronization. Two sorts of electrical coupling are important in modulating or generating various in vitro oscillations: (a) between interneurons, primarily between dendrites; and (b) between axons of pyramidal neurons. VFO can exist in isolation or can act as generators of gamma frequency oscillations. Oscillations at gamma frequencies and below probably create conditions under which synaptic plasticity can occur, between selected neurons-even those separated by significant axonal conduction delays.}, Author = {Traub, Roger D. and Bibbig, Andrea and LeBeau, Fiona E. N. and Buhl, Eberhard H. and Whittington, Miles A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0147-006X}, Journal = {Annu Rev Neurosci}, Keywords = {Synaptic Transmission;24 Pubmed search results 2008;research support, non-u.s. gov't;Biological Clocks;Action Potentials;Hippocampus;Neural Pathways;Neuronal Plasticity;Neural Inhibition;Electrophysiology;research support, u.s. gov't, p.h.s.;Animals;Humans;Interneurons;review;Nerve Net}, Nlm_Id = {7804039}, Organization = {Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA. roger.traub\@downstate.edu}, Pages = {247-78}, Pubmed = {15217333}, Title = {Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro}, Uuid = {70159DBE-9159-4BC8-9CAC-AD0CA2794254}, Volume = {27}, Year = {2004}, url = {papers/Traub_AnnuRevNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.27.070203.144303}} @article{Traub:2001, Abstract = {PURPOSE: We propose an experimentally and clinically testable hypothesis, concerning the origin of very fast (> approximately 70 Hz) EEG oscillations that sometimes precede the onset of focal seizures. These oscillations are important, as they may play a causal role in the initiation of seizures. METHODS: Subdural EEG recordings were obtained from children with focal cortical dysplasias and intractable seizures. Intra- and extracellular recordings were performed in rat hippocampal slices, with induction of population activity, as follows: (a) bath-applied tetramethylamine (an intracellular alkalinizing agent, that opens gap junctions); (b) bath-applied carbachol, a cholinergic agonist; and (c) focal pressure ejection of hypertonic K+ solution. Detailed network simulations were performed, the better to understand the cellular mechanisms underlying oscillations. A major feature of the simulations was inclusion of axon-axon gap junctions between principal neurons, as supported by recent experimental data. RESULTS: Very fast oscillations were found in children before seizure onset, but also superimposed on bursts during the seizure, and on interictal bursts. In slice experiments, very fast oscillations had previously been seen on interictal-like bursts; we now show such oscillations before, between, and after epileptiform bursts. Very fast oscillations were also seen superimposed on gamma (30-70 Hz) oscillations induced by carbachol or hypertonic K+, and in the latter case, very fast oscillations became continuous when chemical synapses were blocked. Simulations replicate these data, when axonal gap junctions are included. CONCLUSIONS: Electrical coupling between principal neurons, perhaps via axonal gap junctions, could underlie very fast population oscillations, in seizure-prone brain, but possibly also in normal brain. The anticonvulsant potential of gap-junction blockers such as carbenoxolone, now in clinical use for treatment of ulcer disease, should be considered.}, Author = {Traub, R. D. and Whittington, M. A. and Buhl, E. H. and LeBeau, F. E. and Bibbig, A. and Boyd, S. and Cross, H. and Baldeweg, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Mice, Inbred BALB C;Animals;Subdural Space;Humans;Rats;Seizures;Brain;Videotape Recording;review;Axons;Rats, Wistar;Gap Junctions;research support, non-u.s. gov't;Neurons;21 Neurophysiology;Mice;Carbenoxolone;24 Pubmed search results 2008;Microelectrodes;21 Gap junctions;Electroencephalography;Electrodes, Implanted}, Month = {2}, Nlm_Id = {2983306R}, Number = {2}, Organization = {Department of Pharmacology, University of Birmingham School of Medicine, Vincent Drive, Edgbaston, Birmingham B15 2TT, UK. r.d.traub\@bham.ac.uk}, Pages = {153-70}, Pii = {epi26900}, Pubmed = {11240585}, Title = {A possible role for gap junctions in generation of very fast EEG oscillations preceding the onset of, and perhaps initiating, seizures}, Uuid = {F732A624-8EA7-4DFE-ADBC-B74C59C8D99F}, Volume = {42}, Year = {2001}, url = {papers/Traub_Epilepsia2001.pdf}} @article{Traub:1999, Abstract = {In hippocampal slices, high-frequency (125-333 Hz) synchronized oscillations have been shown to occur amongst populations of pyramidal neurons, in a manner that is independent of chemical synaptic transmission, but which is dependent upon gap junctions. At the intracellular level, high-frequency oscillations are associated with full-sized action potentials and with fast prepotentials. Using simulations of two pyramidal neurons, we previously argued that the submillisecond synchrony, and the rapid time-course of fast prepotentials, could be explained, in principle, if the requisite gap junctions were located between pyramidal cell axons. Here, we use network simulations (3072 pyramidal cells) to explore further the hypothesis that gap junctions occur between axons and could explain high-frequency oscillations. We show that, in randomly connected networks with an average of two gap junctions per cell, or less, synchronized network bursts can arise without chemical synapses, with frequencies in the experimentally observed range (spectral peaks 125-182 Hz). These bursts are associated with fast prepotentials (or partial spikes and spikelets) as observed in physiological recordings. The critical assumptions we must make for the oscillations to occur are: (i) there is a background of ectopic axonal spikes, which can occur at low frequency (one event per 25 s per axon); (ii) the gap junction resistance is small enough that a spike in one axon can induce a spike in the coupled axon at short latency (in the model, a resistance of 273 M omega works, with an associated latency of 0.25 ms). We predict that axoaxonal gap junctions, in combination with recurrent excitatory synapses, can induce the occurrence of high-frequency population spikes superimposed on epileptiform field potentials.}, Author = {Traub, R. D. and Schmitz, D. and Jefferys, J. G. and Draguhn, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Gap Junctions;research support, non-u.s. gov't;Action Potentials;Hippocampus;Models, Neurological;Presynaptic Terminals;Pyramidal Cells;Nerve Net;Animals;Humans;24 Pubmed search results 2008}, Nlm_Id = {7605074}, Number = {2}, Organization = {Division of Neuroscience, University of Birmingham School of Medicine, Edgbaston, UK.}, Pages = {407-26}, Pii = {S0306-4522(98)00755-6}, Pubmed = {10408594}, Title = {High-frequency population oscillations are predicted to occur in hippocampal pyramidal neuronal networks interconnected by axoaxonal gap junctions}, Uuid = {0534CA85-1D53-41BB-AE0D-BBBB36604BCD}, Volume = {92}, Year = {1999}} @article{Traub:2002, Abstract = {We hypothesized in 1998 that gap junctions might be located between the axons of principal hippocampal neurons, based on the shape of spikelets (fast prepotentials), occurring during gap junction-mediated very fast (to approximately 200 Hz) network oscillations in vitro. More recent electrophysiological, pharmacological and dye-coupling data indicate that axonal gap junctions exist; so far, they appear to be located about 100 microm from the soma, in CA1 pyramidal neurons. Computer modeling and theory predict that axonal gap junctions can lead to very fast network oscillations under three conditions: a) there are spontaneous axonal action potentials; b) the number of gap junctions in the network is neither too low (not less than to approximately 1.5 per cell on average), nor too high (not more than to approximately 3 per cell on average); c) action potentials can cross from axon to axon via gap junctions. Simulated oscillations resemble biological ones, but condition (c) remains to be demonstrated directly. Axonal network oscillations can, in turn, induce oscillatory activity in larger neuronal networks, by a variety of mechanisms. Axonal networks appear to underlie in vivo ripples (to approximately 200 Hz field potential oscillations superimposed on physiological sharp waves), to drive gamma (30-70 Hz) oscillations that appear in the presence of carbachol, and to initiate certain types of ictal discharge. If axonal gap junctions are important for seizure initiation in humans, there could be practical consequences for antiepileptic therapy: at least one gap junction-blocking compound, carbenoxolone, is already in clinical use (for treatment of ulcer disease), and it crosses the blood-brain barrier.}, Author = {Traub, Roger D. and Draguhn, Andreas and Whittington, Miles A. and Baldeweg, Torsten and Bibbig, Andrea and Buhl, Eberhard H. and Schmitz, Dietmar}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0334-1763}, Journal = {Rev Neurosci}, Keywords = {gamma-Aminobutyric Acid;Animals;Evoked Potentials;Humans;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Histamine H2 Antagonists;Neural Conduction;Synaptic Transmission;Excitatory Amino Acid Agonists;Epilepsy;review;Hippocampus;Pyramidal Cells;Calcium;Gap Junctions;research support, non-u.s. gov't;Axons;Nerve Net;21 Neurophysiology;Neurons;21 Gap junctions;Interneurons;Methylamines;Carbenoxolone;in vitro}, Nlm_Id = {8711016}, Number = {1}, Organization = {Department of Physiology, SUNY Downstate Medical Center, Brooklyn 11203, USA. roger.traub\@downstate.edu}, Pages = {1-30}, Pubmed = {12013024}, Title = {Axonal gap junctions between principal neurons: a novel source of network oscillations, and perhaps epileptogenesis}, Uuid = {3F508854-C6AE-43EF-B31B-FD1D478E35B9}, Volume = {13}, Year = {2002}} @article{Traub:1982, Abstract = {Interictal spikes are a simple kind of epileptic neuronal activity. Field potentials and intracellular recordings observed during interictal spikes of penicillin-treated slices of the hippocampus were reproduced by a mathematical model of a network of 100 hippocampal neurons from the region including CA2 and CA3. The model shows that this form of neuronal synchronization arises because of mutual excitation between neurons, each of which is capable of intrinsic bursting in response to a brief input.}, Author = {Traub, R. D. and Wong, R. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Epilepsy;Models, Biological;Penicillins;10 Development;research support, non-u.s. gov't;21 Neurophysiology;Action Potentials;Hippocampus;Time Factors;21 Gap junctions;10 genetics malformation;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008;Neurons;21 Epilepsy}, Month = {5}, Nlm_Id = {0404511}, Number = {4547}, Pages = {745-7}, Pubmed = {7079735}, Title = {Cellular mechanism of neuronal synchronization in epilepsy}, Uuid = {1435CB50-DBA2-4C27-9638-70E8F7834B49}, Volume = {216}, Year = {1982}} @article{Traulsen:2007, Abstract = {BACKGROUND: The basic idea of tag-based models for cooperation is that individuals recognize each other via arbitrary signals, so-called tags. If there are tags of different colors, then cooperators can always establish new signals of recognition. The resulting "chromodynamics" is a mechanism for the evolution of cooperation. Cooperators use a secret tag until they are discovered by defectors who then destroy cooperation based on this tag. Subsequently, a fraction of the population manages to establish cooperation based on a new tag. METHODOLOGY/PRINCIPAL FINDINGS: We derive a mathematical description of stochastic evolutionary dynamics of tag-based cooperation in populations of finite size. Benefit and cost of cooperation are given by b and c. We find that cooperators are more abundant than defectors if b/c > 1+2u/v, where u is the mutation rate changing only the strategy and v is the mutation rate changing strategy and tag. We study specific assumptions for u and v in two genetic models and one cultural model. CONCLUSIONS/SIGNIFICANCE: In a genetic model, tag-based cooperation only evolves if a gene encodes both strategy and tag. In a cultural model with equal mutation rates between all possible phenotypes (tags and behaviors), the crucial condition is b/c > (K+1)/(K-1), where K is the number of tags. A larger number of tags requires a smaller benefit-to-cost ratio. In the limit of many different tags, the condition for cooperators to have a higher average abundance than defectors becomes b > c.}, Author = {Traulsen, Arne and Nowak, Martin A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1932-6203}, Journal = {PLoS ONE}, Keywords = {20 Networks;09 Evolutionary dynamics;24 Pubmed search results 2008}, Nlm_Id = {101285081}, Number = {3}, Organization = {Program for Evolutionary Dynamics, Department of Organismic and Evolutionary Biology, Department of Mathematics, Harvard University, Cambridge, Massachusetts, United States of America. traulsen\@fas.harvard.edu}, Pages = {e270}, Pubmed = {17342204}, Title = {Chromodynamics of cooperation in finite populations}, Uuid = {1319B9DA-8A67-4543-B2AE-6FA5C4161483}, Volume = {2}, Year = {2007}, url = {papers/Traulsen_PLoSONE2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0000270}} @article{Trevelyan:2006, Abstract = {What regulates the spread of activity through cortical circuits? We present here data indicating a pivotal role for a vetoing inhibition restraining modules of pyramidal neurons. We combined fast calcium imaging of network activity with whole-cell recordings to examine epileptiform propagation in mouse neocortical slices. Epileptiform activity was induced by washing Mg2+ ions out of the slice. Pyramidal cells receive barrages of inhibitory inputs in advance of the epileptiform wave. The inhibitory barrages are effectively nullified at low doses of picrotoxin (2.5-5 microM). When present, however, these inhibitory barrages occlude an intense excitatory synaptic drive that would normally exceed action potential threshold by approximately a factor of 10. Despite this level of excitation, the inhibitory barrages suppress firing, thereby limiting further neuronal recruitment to the ictal event. Pyramidal neurons are recruited to the epileptiform event once the inhibitory restraint fails and are recruited in spatially clustered populations (150-250 microm diameter). The recruitment of the cells within a given module is virtually simultaneous, and thus epileptiform events progress in intermittent (0.5-1 Hz) steps across the cortical network. We propose that the interneurons that supply the vetoing inhibition define these modular circuit territories.}, Author = {Trevelyan, Andrew J. and Sussillo, David and Watson, Brendon O. and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Electric Stimulation;Epilepsy;research support, non-u.s. gov't;21 Neurophysiology;GABA Modulators;Action Potentials;Mice, Inbred C57BL;Neural Inhibition;in vitro;Neocortex;comparative study;research support, n.i.h., extramural;Animals;Mice;24 Pubmed search results 2008;Receptors, GABA-A}, Month = {11}, Nlm_Id = {8102140}, Number = {48}, Organization = {Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10027, USA. andytrev\@gmail.com}, Pages = {12447-55}, Pii = {26/48/12447}, Pubmed = {17135406}, Title = {Modular propagation of epileptiform activity: evidence for an inhibitory veto in neocortex}, Uuid = {C3D6040A-4C9F-4E46-A43D-E96843190F66}, Volume = {26}, Year = {2006}, url = {papers/Trevelyan_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2787-06.2006}} @article{Trevelyan:2007, Abstract = {It is still poorly understood how epileptiform events can recruit cortical circuits. Moreover, the speed of propagation of epileptiform discharges in vivo and in vitro can vary over several orders of magnitude (0.1-100 mm/s), a range difficult to explain by a single mechanism. We previously showed how epileptiform spread in neocortical slices is opposed by a powerful feedforward inhibition ahead of the ictal wave. When this feedforward inhibition is intact, epileptiform spreads very slowly (approximately 100 microm/s). We now investigate whether changes in this inhibitory restraint can also explain much faster propagation velocities. We made use of a very characteristic pattern of evolution of ictal activity in the zero magnesium (0 Mg2+) model of epilepsy. With each successive ictal event, the number of preictal inhibitory barrages dropped, and in parallel with this change, the propagation velocity increased. There was a highly significant correlation (p < 0.001) between the two measures over a 1000-fold range of velocities, indicating that feedforward inhibition was the prime determinant of the speed of epileptiform propagation. We propose that the speed of propagation is set by the extent of the recruitment steps, which in turn is set by how successfully the feedforward inhibitory restraint contains the excitatory drive. Thus, a single mechanism could account for the wide range of propagation velocities of epileptiform events observed in vitro and in vivo.}, Author = {Trevelyan, Andrew J. and Sussillo, David and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;research support, n.i.h., extramural;24 Pubmed search results 2008;21 Epilepsy}, Month = {3}, Nlm_Id = {8102140}, Number = {13}, Organization = {Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, New York 10027, USA. andytrev\@gmail.com}, Pages = {3383-7}, Pii = {27/13/3383}, Pubmed = {17392454}, Title = {Feedforward inhibition contributes to the control of epileptiform propagation speed}, Uuid = {3E86D9E7-51D1-441E-ABF8-AFE46AF4A80D}, Volume = {27}, Year = {2007}, url = {papers/Trevelyan_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0145-07.2007}} @article{Trimarchi:2007, Abstract = {During development of the central nervous system (CNS), cycling uncommitted progenitor cells give rise to a variety of distinct neuronal and glial cell types. As these different cell types are born they progress from newly specified cells to fully differentiated neurons and glia. In order to define the developmental processes of individual cell types, single cell expression profiling was carried out on developing ganglion and amacrine cells of the murine retina. Individual cells from multiple developmental stages were isolated and profiled on Affymetrix oligonucleotide arrays. Two-color fluorescent in situ hybridization on dissociated retinas was used to verify and extend the microarray results by allowing quantitative measurements of a large number of cells coexpressing two genes. Together, these experiments have yielded an expanded view of the processes underway in developing retinal ganglion and amacrine cells, as well as several hundred new marker genes for these cell types. In addition, this study has allowed for the definition of some of the molecular heterogeneity both between developing ganglion and amacrine cells and among subclasses of each cell type. J. Comp. Neurol. 502:1047-1065, 2007. (c) 2007 Wiley-Liss, Inc.}, Author = {Trimarchi, Jeffrey M. and Stadler, Michael B. and Roska, Botond and Billings, Nathan and Sun, Ben and Bartch, Brandon and Cepko, Constance L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {10 Development;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0406041}, Number = {6}, Organization = {Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115.}, Pages = {1047-65}, Pubmed = {17444492}, Title = {Molecular heterogeneity of developing retinal ganglion and amacrine cells revealed through single cell gene expression profiling}, Uuid = {6C21F51D-6141-4A76-A8A6-EED4CE5200C4}, Volume = {502}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.21368}} @article{Tripp:2001, Abstract = {Chemokines are chemoattractant proteins that are divided into subfamilies based upon cysteine signature motifs termed C, CC, CXC and CX3C. Chemokines have roles in immunity and inflammation that affect cell trafficking and activation of T cells as well as cells of the innate immune system. We report here CX3C chemokine mimicry for the G glycoprotein of respiratory syncytial virus (RSV) and show binding to CX3CR1--the specific receptor for the CX3C chemokine fractalkine--and induction of leukocyte chemotaxis. We also show that CX3CR1 facilitates RSV infection of cells. Thus, G glycoprotein interaction with CX3CR1 probably plays a key role in the biology of RSV infection.}, Author = {Tripp, R. A. and Jones, L. P. and Haynes, L. M. and Zheng, H. and Murphy, P. M. and Anderson, L. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2908}, Journal = {Nat Immunol}, Keywords = {Chemokines, CX3C;Respiratory Syncytial Viruses;Molecular Sequence Data;Chemotaxis, Leukocyte;Immunity, Natural;T-Lymphocytes;Viral Proteins;11 Glia;Glycoproteins;15 Retrovirus mechanism;Mice;Animals;Lymphocyte Activation;24 Pubmed search results 2008}, Medline = {21370260}, Month = {8}, Nlm_Id = {100941354}, Number = {8}, Organization = {National Centers for Infectious Diseases, Division of Viral and Rickettsial Diseases, Respiratory and Enteric Virus Branch, Mailstop G-09, 1600 Clifton Rd., Atlanta, GA, USA. rgt3\@cdc.gov}, Pages = {732-8}, Pii = {90675}, Pubmed = {11477410}, Title = {CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein}, Uuid = {41114BD2-EE15-11DA-8605-000D9346EC2A}, Volume = {2}, Year = {2001}, url = {papers/Tripp_NatImmunol2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/90675}} @article{Tropea:2003, Abstract = {Damage to the adult CNS often causes devastating and permanent deficits because of the limited capacity of the brain for anatomical reorganization. The finding that collateral sprouting of uninjured fiber tracts mediates recovery of function prompts the search for experimental strategies that stimulate axonal plasticity after CNS trauma. Here we characterize treatments that promote the sprouting of undamaged retinal afferents into the denervated superior colliculus (SC) after a partial retinal lesion in the adult rat. Delivery of brain-derived neurotrophic factor (BDNF) was performed to enhance the intrinsic potential of retinal ganglion cells to reelongate their axons. Reduction of the neurite growth-inhibitory properties of the adult SC was accomplished via treatment with chondroitinase ABC (C-ABC), which degrades chondroitin sulfate proteoglycans. Retinal axons were labeled via intraocular injections of fluorescently tagged cholera toxin B subunit, and fiber sprouting within the denervated SC was measured by quantitative laser-scanning confocal microscopy 1 week after the retinal lesion. We found that both the administration of BDNF and the injection of C-ABC induce significant sprouting of retinal afferents into the collicular scotoma. Remarkably, the combined treatment with BDNF and C-ABC showed synergistic effects on axon growth. Colocalization analysis with anti-synapsin antibodies demonstrated synapse formation by the sprouting axons. These results suggest that the combined treatment with BDNF and C-ABC can be relevant in therapies for the repair of the damaged adult CNS. 1529-2401 Journal Article}, Author = {Tropea, D. and Caleo, M. and Maffei, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Neurosci}, Keywords = {Cholera Toxin;Drug Synergism;Rats, Long-Evans;Animals;Retinal Ganglion Cells/drug effects/physiology;Nerve Fibers/drug effects;Proteochondroitin Sulfates/metabolism;Rats;Denervation;Cell Count;G, L pdf;Brain-Derived Neurotrophic Factor/*pharmacology;11 Glia;Axons/drug effects/physiology;Support, Non-U.S. Gov't;Synapses/drug effects/physiology;Scotoma/physiopathology;Retina/cytology/*drug effects/*physiology;Superior Colliculus/drug effects/*physiology;Drug Administration Routes;Chondroitin ABC Lyase/*pharmacology;Microglia/metabolism/pathology}, Number = {18}, Organization = {Istituto di Neuroscienze del Consiglio Nazionale delle Ricerche, and Scuola Normale Superiore, 56100 Pisa, Italy.}, Pages = {7034-44}, Pubmed = {12904464}, Title = {Synergistic effects of brain-derived neurotrophic factor and chondroitinase ABC on retinal fiber sprouting after denervation of the superior colliculus in adult rats}, Uuid = {F7BCBBD0-6A93-4B4A-BAF7-23AC3E85F413}, Volume = {23}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12904464}} @article{Tropea:2006, Abstract = {Two key models for examining activity-dependent development of primary visual cortex (V1) involve either reduction of activity in both eyes via dark-rearing (DR) or imbalance of activity between the two eyes via monocular deprivation (MD). Combining DNA microarray analysis with computational approaches, RT-PCR, immunohistochemistry and physiological imaging, we find that DR leads to (i) upregulation of genes subserving synaptic transmission and electrical activity, consistent with a coordinated response of cortical neurons to reduction of visual drive, and (ii) downregulation of parvalbumin expression, implicating parvalbumin-expressing interneurons as underlying the delay in cortical maturation after DR. MD partially activates homeostatic mechanisms but differentially upregulates molecular pathways related to growth factors and neuronal degeneration, consistent with reorganization of connections after MD. Expression of a binding protein of insulin-like growth factor-1 (IGF1) is highly upregulated after MD, and exogenous application of IGF1 prevents the physiological effects of MD on ocular dominance plasticity examined in vivo.}, Author = {Tropea, Daniela and Kreiman, Gabriel and Lyckman, Alvin and Mukherjee, Sayan and Yu, Hongbo and Horng, Sam and Sur, Mriganka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, n.i.h., extramural ;Signal Transduction;Animals;Gene Expression Regulation;Neuronal Plasticity;Oligonucleotide Array Sequence Analysis;Visual Pathways;Sensory Deprivation;Vision, Monocular;comparative study ;Darkness;RNA, Messenger;Reverse Transcriptase Polymerase Chain Reaction;Vision, Binocular;research support, non-u.s. gov't ;Animals, Newborn;21 Neurophysiology;Mice;24 Pubmed search results 2008;Immunohistochemistry;Nerve Tissue Proteins;Visual Cortex}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Department of Brain and Cognitive Sciences and Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.}, Pages = {660-8}, Pii = {nn1689}, Pubmed = {16633343}, Title = {Gene expression changes and molecular pathways mediating activity-dependent plasticity in visual cortex}, Uuid = {04E5AB24-D50C-4CD5-8902-D780A87C92D6}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1689}} @article{Tropepe:1999, Abstract = {Multipotent, self-renewing neural stem cells reside in the embryonic mouse telencephalic germinal zone. Using an in vitro neurosphere assay for neural stem cell proliferation, we demonstrate that FGF-responsive neural stem cells are present as early as E8.5 in the anterior neural plate, but EGF-responsive neural stem cells emerge later in development in a temporally and spatially specific manner. By separately blocking EGF and FGF2 signaling, we also show that EGF alone and FGF2 alone can independently elicit neural stem cell proliferation and at relatively high cell densities separate cell nonautonomous effects can substantially enhance the mitogen-induced proliferation. At lower cell densities, neural stem cell proliferation is additive in the presence of EGF and FGF2 combined, revealing two different stem cell populations. However, both FGF-responsive and EGF-responsive neural stem cells retain their self-renewal and multilineage potential, regardless of growth factor conditions. These results support a model in which separate, lineage-related EGF- and FGF-responsive neural stem cells are present in the embryonic telencephalic germinal zone. 99177151 0012-1606 Journal Article}, Author = {Tropepe, V. and Sibilia, M. and Ciruna, B. G. and Rossant, J. and Wagner, E. F. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Dev Biol}, Keywords = {Cell Differentiation;Chimera;Telencephalon/*embryology;Embryo and Fetal Development;Neurons/*metabolism;Animal;C-12b;Epidermal Growth Factor/*pharmacology;Fibroblast Growth Factors/*pharmacology;Receptor, Epidermal Growth Factor/metabolism;Support, Non-U.S. Gov't;Intermediate Filament Proteins/metabolism;Ploidies;04 Adult neurogenesis factors;Receptors, Fibroblast Growth Factor/metabolism;Mice;Immunohistochemistry;Gestational Age;Signal Transduction/physiology;Cell Division/drug effects;Stem Cells/*metabolism}, Number = {1}, Organization = {Department of Anatomy and Cell Biology, University of Toronto, Toronto, M5S 1A8, Canada. v.tropepe\@utoronto.ca}, Pages = {166-88}, Pubmed = {10075850}, Title = {Distinct neural stem cells proliferate in response to EGF and FGF in the developing mouse telencephalon}, Uuid = {BEC16883-816D-47FE-BECB-34FDD727D05E}, Volume = {208}, Year = {1999}, url = {papers/Tropepe_DevBiol1999}} @article{Tropepe:1997, Abstract = {The adult mammalian forebrain subependyma contains neural stem cells and their progeny, the constitutively proliferating progenitor cells. Using bromodeoxyuridine labeling to detect mitotically active cells, we demonstrate that the endogenous expression of transforming growth factor-alpha (TGFalpha) is necessary for the full proliferation of progenitor cells localized to the dorsolateral corner of the subependyma and the full production of the neuronal progenitors that migrate to the olfactory bulbs. Proliferation of these progenitor cells also is diminished with age (in 23- to 25-months-old compared with 2- to 4-months-old mice), likely because of a lengthening of the cell cycle. Senescence or the absence of endogenous TGFalpha does not affect the numbers of neural stem cells isolated in vitro in the presence of epidermal growth factor. These results suggest that endogenous TGFalpha and the effects of senescence may regulate the proliferation of progenitor cells in the adult subependyma, but that the number of neural stem cells is maintained throughout life. 97461629 0270-6474 Journal Article}, Author = {Tropepe, V. and Craig, C. G. and Morshead, C. M. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {J Neurosci}, Keywords = {Prosencephalon/*cytology;Mice, Knockout/genetics;Tissue Culture;Neurons/*cytology/physiology;Cell Cycle;Animal;Cell Count;Cell Movement;Ependyma/*cytology;Aging/*physiology;Stem Cells/*cytology;Time Factors;Male;Support, Non-U.S. Gov't;C-5b;Olfactory Bulb/cytology;Transforming Growth Factor alpha/*deficiency/genetics;04 Adult neurogenesis factors;Mice;Cell Division}, Number = {20}, Organization = {Neurobiology Research Group, Department of Anatomy and Cell Biology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.}, Pages = {7850-9}, Pubmed = {9315905}, Title = {Transforming growth factor-alpha null and senescent mice show decreased neural progenitor cell proliferation in the forebrain subependyma}, Uuid = {A8ABEE22-19ED-4EC9-B845-16D783654795}, Volume = {17}, Year = {1997}, url = {papers/Tropepe_JNeurosci1997.pdf}} @article{Tropepe:2001, Abstract = {Little is known about how neural stem cells are formed initially during development. We investigated whether a default mechanism of neural specification could regulate acquisition of neural stem cell identity directly from embryonic stem (ES) cells. ES cells cultured in defined, low-density conditions readily acquire a neural identity. We characterize a novel primitive neural stem cell as a component of neural lineage specification that is negatively regulated by TGFbeta-related signaling. Primitive neural stem cells have distinct growth factor requirements, express neural precursor markers, generate neurons and glia in vitro, and have neural and non-neural lineage potential in vivo. These results are consistent with a default mechanism for neural fate specification and support a model whereby definitive neural stem cell formation is preceded by a primitive neural stem cell stage during neural lineage commitment. 21243067 0896-6273 Journal Article}, Author = {Tropepe, V. and Hitoshi, S. and Sirard, C. and Mak, T. W. and Rossant, J. and van der Kooy, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {10 Development;Neurons/*cytology/metabolism;Nervous System/cytology/*embryology/*growth &development;Body Patterning/drug effects/*physiology;Animal;Chimera/embryology/genetics/metabolism;Cell Differentiation/drug effects/*physiology;Cell Size/genetics;DNA-Binding Proteins/genetics/metabolism;Cells, Cultured/cytology/drug effects/metabolism;Mammals/*embryology/metabolism;Culture Media, Serum-Free/pharmacology;Signal Transduction/drug effects/physiology;Stem Cells/*cytology/drug effects/metabolism;Growth Substances/deficiency;Support, Non-U.S. Gov't;Cell Lineage/drug effects/*physiology;Intermediate Filament Proteins/drug effects/metabolism;Trans-Activators/genetics/metabolism;Growth Inhibitors/pharmacology;Lymphokines/pharmacology;Transforming Growth Factor beta/drug effects/metabolism;Mice;F}, Number = {1}, Organization = {Department of Anatomy &Cell Biology, University of Toronto, Ontario M5S 1A8, Toronto, Canada.}, Pages = {65-78}, Pubmed = {11343645}, Title = {Direct neural fate specification from embryonic stem cells: a primitive mammalian neural stem cell stage acquired through a default mechanism}, Uuid = {7C53C390-FFEE-476B-9E2C-E0AC12E1A71C}, Volume = {30}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11343645}} @article{Trotter:2006, Abstract = {Malformations of the neocortex are a common cause of human epilepsy; however, the critical issue of how disturbances in cortical organization render neurons epileptogenic remains controversial. The present study addressed this issue by studying inhibitory structure and function before seizure onset in the telencephalic internal structural heterotopia (tish) rat, which is a genetic model of heightened seizure susceptibility associated with a prominent neocortical malformation. Both normally positioned (normotopic) and misplaced (heterotopic) pyramidal neurons in the tish neocortex exhibited lower resting membrane potentials and a tendency toward higher input resistance compared with pyramidal neurons from control brains. GABAergic synaptic transmission was attenuated in the tish cortex, characterized by significant reductions in the frequency of spontaneous IPSCs (sIPSCs) and miniature IPSCs recorded from pyramidal neurons. In addition, the amplitudes of sIPSCs were reduced in the tish neocortex, an effect that was more profound in the normotopic cells. Immunohistochemical assessment of presynaptic GABAergic terminals showed a reduction in terminals surrounding pyramidal cell somata in normotopic and heterotopic tish neocortex. The attenuation of inhibitory innervation was more prominent for normotopic neurons and was associated with a reduction in a subset of GABAergic interneurons expressing the calcium-binding protein parvalbumin. Together, these findings indicate that key facets of inhibitory GABAergic neurotransmission are disturbed before seizure onset in a brain predisposed to developing seizures. Such alterations represent a rational substrate for reduced seizure thresholds associated with certain cortical malformations.}, Author = {Trotter, Stacey A. and Kapur, Jaideep and Anzivino, Matthew J. and Lee, Kevin S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, n.i.h., extramural ;Animals;Humans;Rats;Seizures;Synaptic Transmission;Neocortex;Female;Rats, Sprague-Dawley;comparative study ;21 Dysplasia-heterotopia;Disease Models, Animal;Male;Receptors, GABA-A;Action Potentials;21 Neurophysiology;24 Pubmed search results 2008;Neural Inhibition;Rats, Mutant Strains}, Month = {10}, Nlm_Id = {8102140}, Number = {42}, Organization = {Department of Neuroscience, Health Sciences Center, Neuroscience Graduate Program, University of Virginia, Charlottesville, Virginia 22908, USA.}, Pages = {10756-67}, Pii = {26/42/10756}, Pubmed = {17050714}, Title = {GABAergic synaptic inhibition is reduced before seizure onset in a genetic model of cortical malformation}, Uuid = {740869C6-793B-4744-9E80-448B8D5A3E54}, Volume = {26}, Year = {2006}, url = {papers/Trotter_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2323-06.2006}} @article{Trottier:1994, Abstract = {We present the histologic study of two patients who underwent cerebral cortex resection for partial seizures linked with cortical dysplasia. The distinction of areas of seizure origin from areas of seizure propagation was made according to stereoelectroencephalographic criteria. Samples of epileptogenic tissue were studied by using cytoarchitectonic and immunohistochemical stainings. We mapped the catecholaminergic afferents by employing antisera directed against tyrosine hydroxylase and dopamine-beta-hydroxylase enzymes. The epileptic activity was correlated with the underlying patterns of cytoarchitectonic and immunohistochemical changes. The neuropathological features were focal and consisted of large neurons dispersed through all but the first cortical layer (associated in one case to giant glial cells), of variable disturbance of lamination, of neuronal ectopia in the white matter and of moderate proliferation of small glial cells. Areas of seizure onset coincided with that of dysplastic zones. Both laminar distribution and density of catecholaminergic fibers were altered in the dysplastic cortices (area of seizure onset) and there was an increase in the density of tyrosine hydroxylase-immunoreactive fibers in the surrounding areas of seizure propagation. Our results indicate that these developmental epileptogenic lesions were associated with abnormal neuronal circuitry. They provide evidence at the structural level of the increase in tyrosine hydroxylase activity previously reported in spiking areas of human epileptogenic cerebral cortex and they suggest that catecholamines may contribute toward limiting seizure activity propagation.}, Author = {Trottier, S. and Evrard, B. and Biraben, A. and Chauvel, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0920-1211}, Journal = {Epilepsy Res}, Keywords = {10 Development;case reports;Magnetic Resonance Imaging;Epilepsies, Partial;Humans;Cadaver;Dopamine beta-Hydroxylase;Female;Child;Reference Values;Catecholamines;Male;10 genetics malformation;Cerebral Cortex;Tyrosine 3-Monooxygenase;Immunohistochemistry;Nerve Fibers;24 Pubmed search results 2008;Electroencephalography;Adolescent}, Month = {10}, Nlm_Id = {8703089}, Number = {2}, Organization = {CJF 90-12 INSERM, CHR Pontchaillou, Rennes, France.}, Pages = {161-79}, Pii = {0920-1211(94)90026-4}, Pubmed = {7843171}, Title = {Altered patterns of catecholaminergic fibers in focal cortical dysplasia in two patients with partial seizures}, Uuid = {2832C502-341C-4BCB-9206-91E08EC83166}, Volume = {19}, Year = {1994}} @article{Trotts:2007, Abstract = {Conventional microscopy, electron microscopy, and imaging techniques such as MRI and PET commonly generate large stacks of images of the sectioned brain. In other domains, such as neurophysiology, variables such as space or time are also varied along a stack axis. Digital image sizes have been progressively increasing and in virtual microscopy, it is now common to work with individual image sizes that are several hundred megapixels and several gigabytes in size. The interactive visualization of these high-resolution, multiresolution images in 2D has been addressed previously [Sullivan, G., and Baker, R., 1994. Efficient quad-tree coding of images and video. IEEE Trans. Image Process. 3 (3), 327-331]. Here, we describe a method for interactive visualization of multiresolution image stacks in 3D. The method, characterized as quad-tree based multiresolution image stack interactive visualization using a texel projection based criterion, relies on accessing and projecting image tiles from multiresolution image stacks in such a way that, from the observer's perspective, image tiles all appear approximately the same size even though they are accessed from different tiers within the images comprising the stack. This method enables efficient navigation of high-resolution image stacks. We implement this method in a program called StackVis, which is a Windows-based, interactive 3D multiresolution image stack visualization system written in C++ and using OpenGL. It is freely available at http://brainmaps.org.}, Author = {Trotts, Issac and Mikula, Shawn and Jones, Edward G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1053-8119}, Journal = {Neuroimage}, Keywords = {24 Pubmed search results 2008;23 Technique}, Month = {4}, Nlm_Id = {9215515}, Number = {3}, Organization = {Center for Neuroscience, University of California, Davis, CA 95618, USA.}, Pages = {1038-43}, Pii = {S1053-8119(07)00034-1}, Pubmed = {17336095}, Title = {Interactive visualization of multiresolution image stacks in 3D}, Uuid = {050F2B61-D8A0-4C86-BBEE-3FF47A5F79F5}, Volume = {35}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroimage.2007.01.013}} @article{Trujillo:2007, Abstract = {Although protein receptors on the plasma membrane involved in the initial steps of productive HIV-1 infection have been well characterized, little is known about interactions between cellular carbohydrate receptors and HIV-1. Here, we report the involvement of a carbohydrate receptor, the macrophage mannose receptor (MR), and its role in supporting HIV-1 binding and entry. HIV-1 can enter the cytoplasm of human macrophages and microglia as well as murine macrophages by MR, although no subsequent viral replication was observed. Correspondingly, HIV-1 entry into Cos-7 cells after induction of expression of MR by transfection with MR-cDNA did not demonstrate viral replication. Our studies suggest that whereas MR may serve as a binding and an entry site, the MR-mediated pathway does not lead to productive HIV-1 infection. In addition, we report that recombinant HIV-1 gp120 blocks MR-mediated phagocytosis in human and murine alveolar macrophages and microglial cells. Therefore, characterization of the HIV-1 noninfectious MR-mediated phagocytic pathway may foster advances in HIV-1 vaccine design and an improved understanding of HIV-1/AIDS pathogenesis and host defenses.}, Author = {Trujillo, and Rogers, and Molina, and Dangond, and McLane, and Essex, and Brain,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7505876}, Organization = {Molecular and Integrative Physiological Sciences, Department of Environmental Health, Department of Immunology and Infectious Diseases, and Biomedical Imaging Laboratory, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115.}, Pii = {0611263104}, Pubmed = {17360361}, Title = {Noninfectious entry of HIV-1 into peripheral and brain macrophages mediated by the mannose receptor}, Uuid = {21F7E793-F954-48AB-852F-59A667AB2679}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0611263104}} @article{Truman:2004, Abstract = {In Drosophila most thoracic neuroblasts have two neurogenic periods: an initial brief period during embryogenesis and a second prolonged phase during larval growth. This study focuses on the adult-specific neurons that are born primarily during the second phase of neurogenesis. The fasciculated neurites arising from each cluster of adult-specific neurons express the cell-adhesion protein Neurotactin and they make a complex scaffold of neurite bundles within the thoracic neuropils. Using MARCM clones, we identified the 24 lineages that make up the scaffold of a thoracic hemineuromere. Unlike the early-born neurons that are strikingly diverse in both form and function, the adult specific cells in a given lineage are remarkably similar and typically project to only one or two initial targets, which appear to be the bundled neurites from other lineages. Correlated changes in the contacts between the lineages in different segments suggest that these initial contacts have functional significance in terms of future synaptic partners. This paper provides an overall view of the initial connections that eventually lead to the complex connectivity of the bulk of the thoracic neurons.}, Author = {Truman, James W. and Schuppe, Hansj{\"u}rgen and Shepherd, David and Williams, Darren W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Membrane Glycoproteins;Research Support, Non-U.S. Gov't;Central Nervous System;Larva;Research Support, U.S. Gov't, P.H.S.;Drosophila Proteins;Drosophila;Animals;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8701744}, Number = {20}, Organization = {Department of Biology, University of Washington, Seattle, WA 98195, USA. jwt\@u.washington.edu}, Pages = {5167-84}, Pii = {131/20/5167}, Pubmed = {15459108}, Title = {Developmental architecture of adult-specific lineages in the ventral CNS of Drosophila}, Uuid = {FFA13D7A-3CC6-4033-BF89-E50E1BA2E7BE}, Volume = {131}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.01371}} @article{Tsai:2005, Abstract = {Mutations in the human LIS1 gene cause the smooth brain disease classical lissencephaly. To understand the underlying mechanisms, we conducted in situ live cell imaging analysis of LIS1 function throughout the entire radial migration pathway. In utero electroporation of LIS1 small interference RNA and short hairpin dominant negative LIS1 and dynactin cDNAs caused a dramatic accumulation of multipolar progenitor cells within the subventricular zone of embryonic rat brains. This effect resulted from a complete failure in progression from the multipolar to the migratory bipolar state, as revealed by time-lapse analysis of brain slices. Surprisingly, interkinetic nuclear oscillations in the radial glial progenitors were also abolished, as were cell divisions at the ventricular surface. Those few bipolar cells that reached the intermediate zone also exhibited a complete block in somal translocation, although, remarkably, process extension persisted. Finally, axonal growth also ceased. These results identify multiple distinct and novel roles for LIS1 in nucleokinesis and process dynamics and suggest that nuclear position controls neural progenitor cell division.}, Author = {Tsai, Jin-Wu W. and Chen, Yu and Kriegstein, Arnold R. and Vallee, Richard B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0021-9525}, Journal = {J Cell Biol}, Keywords = {10 Development}, Month = {9}, Nlm_Id = {0375356}, Number = {6}, Organization = {Department of Pathology and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.}, Pages = {935-45}, Pii = {jcb.200505166}, Pubmed = {16144905}, Title = {LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stages}, Uuid = {49B2E577-3563-452C-81C2-B653D20A5571}, Volume = {170}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1083/jcb.200505166}} @article{Tsai:2007, Abstract = {During brain development, neural precursor cells migrate along radial glial fibers to populate the neocortex. RNA interference (RNAi) of the lissencephaly gene LIS1 (also known as PAFAH1b1) inhibits somal movement but not process extension of neural precursors in live brain slices. Here we report imaging of the subcellular events accompanying neural precursor migration and the effects of LIS1, cytoplasmic dynein and myosin II inhibition. Centrosomes move continuously and often far in advance of nuclei, which show extreme saltatory behavior. LIS1 and dynein RNAi inhibit centrosomal and nuclear movement independently, whereas myosin II inhibition blocks only nuclear translocation. Imaging of the microtubule end-binding protein 3 (EB3) reveals a centrosome-centered array of microtubules in live neural precursors under all conditions examined. Dynein is concentrated both at a swelling in the leading process reported to initiate each migratory cycle and in the soma. Thus, dynein pulls on the microtubule network from the swelling. The nucleus is transported along the trailing microtubules by dynein assisted by myosin II.}, Author = {Tsai, Jin-Wu W. and Bremner, K. Helen and Vallee, Richard B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Microtubule-Associated Proteins;Animals;Humans;Rats;Myosin Type II;Microscopy, Confocal;Intracellular Space;Electroporation;Cell Movement;Organ Culture Techniques;research support, non-u.s. gov't;Time Factors;Embryo;Cerebral Cortex;Neurons;Heterocyclic Compounds with 4 or More Rings;research support, n.i.h., extramural;Mice;Dynein ATPase;24 Pubmed search results 2008;Luminescent Proteins;Stem Cells;Nerve Tissue Proteins;Oligonucleotides, Antisense;in vitro}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {Integrated Program in Cellular, Molecular and Biophysical Studies, Columbia University, 630 W 168th Street, New York, New York 10032, USA.}, Pages = {970-9}, Pii = {nn1934}, Pubmed = {17618279}, Title = {Dual subcellular roles for LIS1 and dynein in radial neuronal migration in live brain tissue}, Uuid = {37271B18-460C-4C14-8380-55CEBF98FE84}, Volume = {10}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1934}} @article{Tsai:2005a, Abstract = {Neuronal migration is a critical phase of nervous system development and can be divided into two distinct phases: extension of the leading process and movement of the cell body and nucleus (nucleokinesis). Nucleokinesis appears to require many of the same cytoskeletal and signaling molecules used in cell mitosis. Converging studies suggest it requires cytoplasmic dynein, cell polarity genes, and microtubule-associated proteins that coordinate microtubule remodeling. These coordinate first the positioning of the centrosome (microtubule organizing center) in the leading process in front of the nucleus and then the movement of the nucleus towards the centrosome. The positioning of the centrosome and the dynamic regulation that couples and uncouples the nucleus underlies directed migration of neurons.}, Author = {Tsai, Li-Huei H. and Gleeson, Joseph G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Pathology, Harvard Medical School, Howard Hughes Medical Institute, 77 Avenue Louis Pasteur, Room 858C, Boston, Massachusetts 02115.}, Pages = {383-8}, Pii = {S0896-6273(05)00349-1}, Pubmed = {15882636}, Title = {Nucleokinesis in neuronal migration}, Uuid = {D5CC1906-6426-4CFF-A303-F399BE26AA81}, Volume = {46}, Year = {2005}, url = {papers/Tsai_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.04.013}} @article{Tsau:1999, Abstract = {The initiation site for triggering epileptiform activity was investigated via optical imaging using voltage-sensitive dyes in the neocortical slice perfused with artificial cerebral spinal fluid containing nominally zero magnesium. The neocortical slices (400-microm thick) were harvested from Sprague-Dawley rats (P21-28). Optical imaging was made by using a high speed photodiode array. Spontaneous epileptiform activity emerged 20-40 min after the preparation was perfused with zero-magnesium solution. There was a good correspondence between electrical and optical signals (n = 46), although the details of the two recordings were somewhat different. The initiation sites were measured optically in 11 preparations. Among them, four were found to be located in superficial layers, two were found in middle layers, and five were found in deep layers. Repeated recordings revealed that these initiation sites were relatively stable; shifting of the initiation site was not observed. Therefore spontaneous epileptiform activity could be initiated in various cortical layers, from layer I to layer VI. The activation started from a small area <0.04 mm(3) and spread smoothly from the initiation site to adjacent cortical areas, suggesting that the initiation site is very confined to one of the cortical layers. The initiation sites were distributed randomly in various cortical areas, and no higher probability was found in a special cortical region. Electrical stimulation delivered via a glass microelectrode filled with 2 M NaCl (2-5 MOhms) could reliably trigger epileptiform activity that had the same characteristics as the spontaneous activity. The cortical neurons activated directly by the stimulation were around the electrode's tip and estimated to be within a 50-microm area, suggesting that only a few neurons were needed to form an initiation site. Because the timing for stimulation was arbitrary and the evoked events were initiated independent of discharges of neurons in any other layers, it is likely that the initiation site for epileptiform activity in various cortical layers is independent of the control of layer V pyramidal neurons. Together these finding suggest that the epileptiform focus is confined and can be formed in several (probably all) neocortical layers and in many cortical areas. The initiating neurons may be of different types because neuronal types in various cortical layers are different.}, Author = {Tsau, Y. and Guan, L. and Wu, J. Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Coloring Agents;Microscopy, Interference;Electric Stimulation;Electrophysiology;In Vitro;Animals;Rats;Research Support, U.S. Gov't, Non-P.H.S.;Neocortex;Female;Epilepsy;Rats, Sprague-Dawley;21 Epilepsy;Male;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {99445759}, Month = {10}, Nlm_Id = {0375404}, Number = {4}, Organization = {Georgetown Institute for Cognitive and Computational Sciences, Georgetown University Medical Center, Washington, DC 20007, USA.}, Pages = {1965-73}, Pubmed = {10515986}, Title = {Epileptiform activity can be initiated in various neocortical layers: an optical imaging study}, Uuid = {70775973-FA2A-4A58-8267-6E049E9F4A40}, Volume = {82}, Year = {1999}} @article{Tsay:2004, Abstract = {Dendritic spines mediate most excitatory inputs in the brain, yet their function is still unclear. Imaging experiments have demonstrated their role in biochemical compartmentalization at individual synapses, yet theoretical studies have suggested that they could serve an electrical function in transforming synaptic inputs and transmitting dendritic spikes. Recent data indicate that spines possess voltage-dependent conductances and that these channels can be spine-specific. Although direct experimental investigations of the electrical properties of spines have not yet taken place, spines could play a significant electrical role, greatly influencing dendritic integration and the function of neural circuits.}, Author = {Tsay, David and Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0166-2236}, Journal = {Trends Neurosci}, Keywords = {Brain;24 Pubmed search results 2008;Electric Conductivity;Research Support, Non-U.S. Gov't;Dendrites;21 Neurophysiology;Comparative Study;Models, Neurological;Research Support, U.S. Gov't, P.H.S.;21 Calcium imaging;Calcium;Electrophysiology;Animals;Humans;Membrane Potentials;Neurons;review}, Month = {2}, Nlm_Id = {7808616}, Number = {2}, Organization = {Department of Biological Sciences, Columbia University, 1002 Fairchild, New York, NY 10032, USA. dt133\@columbia.edu}, Pages = {77-83}, Pii = {S0166223603003849}, Pubmed = {15102486}, Title = {On the electrical function of dendritic spines}, Uuid = {ED325D41-9F21-4A0A-B9F9-9B2F7E03004E}, Volume = {27}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tins.2003.11.008}} @article{Tschuluun:2005, Abstract = {Neuronal migration disorders (NMDs) are often associated with medically intractable epilepsy. In utero injection of methylazoxymethanol acetate into pregnant rats gives rise to dysplastic cell clusters ("heterotopia") in hippocampus (and nearby regions), providing an animal model of NMD. In the present study, we have examined the structural and functional integration of hippocampal heterotopic cells into circuits that link the heterotopia with surrounding "normal" brain. Bi-directional morphological connectivity between the heterotopia and hippocampus/neocortex was demonstrated using the neurotracer, biotinylated dextran amine. Single cell recordings in hippocampal slices showed that heterotopia neurons form functional connections with the surrounding hippocampus and neocortex. However, simultaneous field recordings from the CA1 heterotopia, normotopic hippocampus, and neocortex indicated that epileptiform discharges (spontaneous events seen in slices bathed with high [K+]o and bicuculline) were rarely initiated in the heterotopia (although the heterotopia was capable of generating epileptiform discharges independently of normal brain regions). Further, in most of the experiments, the aberrant connectivity provided by CA1 heterotopia failed to function as a "bridge" for epileptiform discharges to propagate directly from low-threshold hippocampus to neocortex. These data do not support the hypothesis that NMDs (heterotopic cell populations) serve as a focus and/or trigger for epileptiform activity, and/or facilitate propagation of epileptiform events.}, Author = {Tschuluun, N. and Wenzel, J. H. and Katleba, K. and Schwartzkroin, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Fluorescent Dyes;Pregnancy;Electrophysiology;Animals;Rats;Dextrans;Neural Pathways;21 Epilepsy;Neocortex;Female;Epilepsy;Rats, Sprague-Dawley;Hippocampus;Abnormalities, Drug-Induced;Brain Diseases;Bicuculline;Teratogens;Research Support, U.S. Gov't, P.H.S.;Potassium;21 Neurophysiology;Methylazoxymethanol Acetate;GABA Antagonists;24 Pubmed search results 2008;Immunohistochemistry;Research Support, N.I.H., Extramural;Biotin}, Nlm_Id = {7605074}, Number = {1}, Organization = {Department of Neurological Surgery, University of California, Davis, Medical Neuroscience Building, Room 612G, 1515 Newton Court, Davis, CA 95616, USA.}, Pages = {327-42}, Pii = {S0306-4522(05)00220-4}, Pubmed = {15893654}, Title = {Initiation and spread of epileptiform discharges in the methylazoxymethanol acetate rat model of cortical dysplasia: functional and structural connectivity between CA1 heterotopia and hippocampus/neocortex}, Uuid = {C5661116-520C-4B72-9941-6C6BD926E4A8}, Volume = {133}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2005.02.009}} @article{Tsodyks:2000, Abstract = {Throughout the neocortex, groups of neurons have been found to fire synchronously on the time scale of several milliseconds. This near coincident firing of neurons could coordinate the multifaceted information of different features of a stimulus. The mechanisms of generating such synchrony are not clear. We simulated the activity of a population of excitatory and inhibitory neurons randomly interconnected into a recurrent network via synapses that display temporal dynamics in their transmission; surprisingly, we found a behavior of the network where action potential activity spontaneously self-organized to produce highly synchronous bursts involving virtually the entire network. These population bursts were also triggered by stimuli to the network in an all-or-none manner. We found that the particular intensities of the external stimulus to specific neurons were crucial to evoke population bursts. This topographic sensitivity therefore depends on the spectrum of basal discharge rates across the population and not on the anatomical individuality of the neurons, because this was random. These results suggest that networks in which neurons are even randomly interconnected via frequency-dependent synapses could exhibit a novel form of reflex response that is sensitive to the nature of the stimulus as well as the background spontaneous activity.}, Author = {Tsodyks, M. and Uziel, A. and Markram, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;Research Support, Non-U.S. Gov't;21 Neurophysiology;Action Potentials;Neuronal Plasticity;Models, Neurological;Nerve Net;24 Pubmed search results 2008;Neurons}, Medline = {20276368}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Department of Neurobiology, Weizmann Institute of Science, Rehovot 76100, Israel. bnmisha\@wicc.weizmann.ac.il}, Pages = {RC50}, Pubmed = {10627627}, Title = {Synchrony generation in recurrent networks with frequency-dependent synapses}, Uuid = {914CD5D5-E115-4190-A6EB-C79F063BE2A8}, Volume = {20}, Year = {2000}} @article{Tsuchida:1974, Abstract = {0042-6822 Journal Article}, Author = {Tsuchida, N. and Green, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Virology}, Keywords = {Nucleic Acid Denaturation;Phosphorus Radioisotopes;*Moloney murine leukemia virus;Mice;RNA, Viral/*analysis;EE, DMSO, abstr;Rats;Cell Line;08 Aberrant cell cycle;*Cell Transformation, Neoplastic;Electrophoresis, Polyacrylamide Gel;Tritium;Animals;Dimethyl Sulfoxide;Nucleic Acid Hybridization;Hamsters;Centrifugation, Density Gradient}, Number = {1}, Pages = {258-65}, Pubmed = {4826208}, Title = {Intracellular and virion 35 S RNA species of murine sarcoma and leukemia viruses}, Uuid = {67D425E1-3206-4E3F-9696-7A2CD7699548}, Volume = {59}, Year = {1974}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4826208}} @article{Tsuchiya:2005, Abstract = {We derived microglia from mouse embryonic stem cells (ES cells) at very high density. Using the markers Mac1(+)/CD45(low) and Mac1(+)/CD45(high) to define microglia and macrophages, respectively, we show that Mac1(+) cells are induced by GM-CSF stimulation following neuronal differentiation of mouse ES cells using a five-step method. CD45(low) expression was high and CD45(high) expression was low on induced cells. We used a density gradient method to obtain a large amount of microglia-like cells, approximately 90\%of Mac1(+) cells. Microglia-like cells expressed MHC class I, class II, CD40, CD80, CD86, and IFN-gammaR. The expression level of these molecules on microglia-like cells was barely enhanced by IFN-gamma. Intravenously transferred GFP(+) microglia derived from GFP(+) ES cells selectively accumulated in brain but not in peripheral tissues such as spleen and lymph node. GFP(+) cells were detected mainly in corpus callosum and hippocampus but were rarely seen in cerebral cortex, where Iba1, another marker of microglia, is primarily expressed. Furthermore, both GFP(+) and Iba1(+) cells exhibited a ramified morphology characteristic of mature microglia. These studies suggest that ES cell-derived microglia-like cells obtained using our protocol are functional and migrate selectively into the brain but not into peripheral tissues after intravenous transplantation.}, Author = {Tsuchiya, Takahiro and Park, Kae Chang and Toyonaga, Shinichi and Yamada, Shoko M. and Nakabayashi, Hiromichi and Nakai, Eiichi and Ikawa, Naoki and Furuya, Masato and Tominaga, Akira and Shimizu, Keiji}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Month = {3}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Neurosurgery, Kochi Medical School, Kochi University, Kohasu, Okoh-cho, Nankoku, Kochi 783-8505 Japan.}, Pages = {210-8}, Pii = {S0165-5728(04)00404-7}, Pubmed = {15710475}, Title = {Characterization of microglia induced from mouse embryonic stem cells and their migration into the brain parenchyma}, Uuid = {BAA1C220-C26D-11DA-969D-000D9346EC2A}, Volume = {160}, Year = {2005}, url = {papers/Tsuchiya_JNeuroimmunol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneuroim.2004.10.025}} @article{Tukker:2007, Abstract = {Cortical gamma oscillations contribute to cognitive processing and are thought to be supported by perisomatic-innervating GABAergic interneurons. We performed extracellular recordings of identified interneurons in the hippocampal CA1 area of anesthetized rats, revealing that the firing patterns of five distinct interneuron types are differentially correlated to spontaneous gamma oscillations. The firing of bistratified cells, which target dendrites of pyramidal cells coaligned with the glutamatergic input from hippocampal area CA3, is strongly phase locked to field gamma oscillations. Parvalbumin-expressing basket, axo-axonic, and cholecystokinin-expressing interneurons exhibit moderate gamma modulation, whereas the spike timing of distal dendrite-innervating oriens-lacunosum moleculare interneurons is not correlated to field gamma oscillations. Cholecystokinin-expressing interneurons fire earliest in the gamma cycle, a finding that is consistent with their suggested function of thresholding individual pyramidal cells. Furthermore, we show that field gamma amplitude correlates with interneuronal spike-timing precision and firing rate. Overall, our recordings suggest that gamma synchronization in vivo is assisted by temporal- and domain-specific GABAergic inputs to pyramidal cells and is initiated in pyramidal cell dendrites in addition to somata and axon initial segments.}, Author = {Tukker, John J. and Fuentealba, Pablo and Hartwich, Katja and Somogyi, Peter and Klausberger, Thomas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;Biological Clocks;Rats, Sprague-Dawley;Action Potentials;Hippocampus;Pyramidal Cells;Rats;comparative study;Interneurons;Animals;Male;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {31}, Organization = {Medical Research Council Anatomical Neuropharmacology Unit, Oxford University, Oxford OX1 3TH, United Kingdom.}, Pages = {8184-9}, Pii = {27/31/8184}, Pubmed = {17670965}, Title = {Cell type-specific tuning of hippocampal interneuron firing during gamma oscillations in vivo}, Uuid = {7962E7FB-2910-483B-8151-CF7D77ECC118}, Volume = {27}, Year = {2007}, url = {papers/Tukker_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1685-07.2007}} @article{Turlejski:2002, Abstract = {In this chapter we provide an extensive review of 100 years of research on the stability of neurons in the mammalian brain, with special emphasis on humans. Although Cajal formulated the Neuronal Doctrine, he was wrong in his beliefs that adult neurogenesis did not occur and adult neurons are dying throughout life. These two beliefs became accepted "common knowledge" and have shaped much of neuroscience research and provided much of the basis for clinical treatment of age-related brain diseases. In this review, we consider adult neurogenesis from a historical and evolutionary perspective. It is concluded, that while adult neurogenesis is a factor in the dynamics of the dentate gyrus and olfactory bulb, it is probably not a major factor during the life-span in most brain areas. Likewise, the acceptance of neuronal death as an explanation for normal age-related senility is challenged with evidence collected over the last fifty years. Much of the problem in changing this common belief of dying neurons was the inadequacies of neuronal counting methods. In this review we discuss in detail implications of recent improvements in neuronal quantification. We conclude: First, age-related neuronal atrophy is the major factor in functional deterioration of existing neurons and could be slowed down, or even reversed by various pharmacological interventions. Second, in most cases neuronal degeneration during aging is a pathology that in principle may be avoided. Third, loss of myelin and of the white matter is more frequent and important than the limited neuronal death in normal aging.}, Author = {Turlejski, Kris and Djavadian, Ruzanna}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0079-6123}, Journal = {Prog Brain Res}, Keywords = {Aging;24 Pubmed search results 2008;Cell Differentiation;Research Support, Non-U.S. Gov't;Central Nervous System;Nerve Degeneration;Cell Division;Cell Death;Nerve Fibers, Myelinated;Humans;Animals;Neurons;review}, Medline = {22139342}, Nlm_Id = {0376441}, Organization = {Department of Neurophysiology, Nencki Institute of Experimental Biology, 3 Pasteur Street, 02-093 Warsaw, Poland. krist\@nencki.gov.pl}, Pages = {39-65}, Pubmed = {12143397}, Title = {Life-long stability of neurons: a century of research on neurogenesis, neuronal death and neuron quantification in adult CNS}, Uuid = {C4AF9723-3E39-4F72-92C5-987DBCA729E1}, Volume = {136}, Year = {2002}} @article{Turrigiano:2006, Abstract = {Homeostatic synaptic plasticity is thought to have a crucial role in stabilizing the activity of neurons and networks, but the mechanisms are poorly understood. In a recent study, Stellwagen and Malenka have shown that synaptic scaling can be induced by activity-dependent changes in release of the cytokine tumor necrosis factor-alpha (TNF-alpha) and, surprisingly, that the source of TNF-alpha is glia rather than neurons. In addition to provide insight into the mechanisms of homeostatic plasticity, these data argue for the first time for an equal partnership between glial cells and neurons in the generation of an important form of synaptic plasticity.}, Author = {Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1471-4914}, Journal = {Trends Mol Med}, Keywords = {Models, Biological;Synapses;Mice, Knockout;Neuroglia;Homeostasis;Neuronal Plasticity;Signal Transduction;Tumor Necrosis Factor-alpha;Animals;Mice;24 Pubmed search results 2008;Neurons;Receptors, Glutamate}, Month = {10}, Nlm_Id = {100966035}, Number = {10}, Organization = {Department of Biology, Brandeis University, Waltham, MA 02454, USA. turrigiano\@brandeis.edu}, Pages = {458-60}, Pii = {S1471-4914(06)00171-7}, Pubmed = {16931159}, Title = {More than a sidekick: glia and homeostatic synaptic plasticity}, Uuid = {F77BF962-EE1D-4F34-93C4-9901A2E54FED}, Volume = {12}, Year = {2006}, url = {papers/Turrigiano_TrendsMolMed2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.molmed.2006.08.002}} @article{Tyzio:2003, Abstract = {A depolarized resting membrane potential has long been considered to be a universal feature of immature neurons. Despite the physiological importance, the underlying mechanisms of this developmental phenomenon are poorly understood. Using perforated-patch, whole cell, and cell-attached recordings, we measured the membrane potential in CA3 pyramidal cells in hippocampal slices from postnatal rats. With gramicidin perforated-patch recordings, membrane potential was -44 +/- 4 (SE) mV at postnatal days P0-P2, and it progressively shifted to -67 +/- 2 mV at P13-15. A similar developmental change of the membrane potential has been also observed with conventional whole cell recordings. However, the value of the membrane potential deduced from the reversal potential of N-methyl-d-aspartate channels in cell-attached recordings did not change with age and was -77 +/- 2 mV at P2 and -77 +/- 2 mV at P13-14. The membrane potential measured using whole cell recordings correlated with seal and input resistance, being most depolarized in neurons with high, several gigaohms, input resistance and low seal resistance. Simulations revealed that depolarized values of the membrane potential in whole cell and perforated-patch recordings could be explained by a shunt through the seal contact between the pipette and membrane. Thus the membrane potential of CA3 pyramidal cells appears to be strongly negative at birth and does not change during postnatal development.}, Author = {Tyzio, Roman and Ivanov, Anton and Bernard, Cristophe and Holmes, Gregory L. and Ben-Ari, Yehezkiel and Khazipov, Roustem}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Research Support, Non-U.S. Gov't;21 Neurophysiology;Rats;Hippocampus;Female;Research Support, U.S. Gov't, P.H.S.;Pyramidal Cells;Rats, Wistar;Animals, Newborn;Nerve Net;Animals;Male;24 Pubmed search results 2008;Membrane Potentials;21 Epilepsy}, Medline = {22980207}, Month = {11}, Nlm_Id = {0375404}, Number = {5}, Organization = {Institut de la Neurobiologie de la M{\'e}ditterran{\'e}e-Institute National de la Sant{\'e} et de la Recherche M{\'e}dicale U29, Marseille, France.}, Pages = {2964-72}, Pii = {00172.2003}, Pubmed = {12867526}, Title = {Membrane potential of CA3 hippocampal pyramidal cells during postnatal development}, Uuid = {4ED2D7BD-7FA6-4BA4-ADF4-3289B54AC97E}, Volume = {90}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00172.2003}} @article{Tyzio:1999, Abstract = {We have performed a morphofunctional analysis of CA1 pyramidal neurons at birth to examine the sequence of formation of GABAergic and glutamatergic postsynaptic currents (PSCs) and to determine their relation to the dendritic arborization of pyramidal neurons. We report that at birth pyramidal neurons are heterogeneous. Three stages of development can be identified: (1) the majority of the neurons (80\%) have small somata, an anlage of apical dendrite, and neither spontaneous nor evoked PSCs; (2) 10\%of the neurons have a small apical dendrite restricted to the stratum radiatum and PSCs mediated only by GABA(A) receptors; and (3) 10\%of the neurons have an apical dendrite that reaches the stratum lacunosum moleculare and PSCs mediated both by GABA(A) and glutamate receptors. These three groups of pyramidal neurons can be differentiated by their capacitance (C(m) = 17.9 +/- 0.8; 30.2 +/- 1.6; 43.2 +/- 3.0 pF, respectively). At birth, the synaptic markers synapsin-1 and synaptophysin labeling are present in dendritic layers but not in the stratum pyramidale, suggesting that GABAergic peridendritic synapses are established before perisomatic ones. The present observations demonstrate that GABAergic and glutamatergic synapses are established sequentially with GABAergic synapses being established first most likely on the apical dendrites of the principal neurons. We propose that different sets of conditions are required for the establishment of functional GABA and glutamate synapses, the latter necessitating more developed neurons that have apical dendrites that reach the lacunosum moleculare region.}, Author = {Tyzio, R. and Represa, A. and Jorquera, I. and Ben-Ari, Y. and Gozlan, H. and Aniksztejn, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {gamma-Aminobutyric Acid;Cell Aging;Electrophysiology;Animals;Synapses;In Vitro;Rats;Glutamic Acid;21 Epilepsy;Hippocampus;Pyramidal Cells;Rats, Wistar;Time Factors;Male;Dendrites;Animals, Newborn;21 Neurophysiology;24 Pubmed search results 2008;Biological Markers;Research Support, Non-U.S. Gov't}, Medline = {20044894}, Month = {12}, Nlm_Id = {8102140}, Number = {23}, Organization = {Institut de Neurobiologie de la M{\'e}dit{\'e}rran{\'e}e, Institut National de la Sant{\'e}, et de la Recherche M{\'e}dicale, 13273 Marseille Cedex 09, France.}, Pages = {10372-82}, Pubmed = {10575034}, Title = {The establishment of GABAergic and glutamatergic synapses on CA1 pyramidal neurons is sequential and correlates with the development of the apical dendrite}, Uuid = {FBEBF37F-D067-11DA-8A8C-000D9346EC2A}, Volume = {19}, Year = {1999}} @article{Uesaka:2007, Abstract = {Target and activity-dependent mechanisms of axonal branching were studied in the thalamocortical (TC) projection using organotypic cocultures of the thalamus and cortex. TC axons were labeled with enhanced yellow fluorescent protein (EYFP) by a single-cell electroporation method and observed over time by confocal microscopy. Changes in the firing activity of cocultures grown on multielectrode dishes were also monitored over time. EYFP-labeled TC axons exhibited more branch formation in and around layer 4 of the cortical explant during the second week in vitro, when spontaneous firing activity increased in both thalamic and cortical cells. Time-lapse imaging further demonstrated that branching patterns were generated dynamically by addition and elimination with a bias toward branch accumulation in the target layer. To examine the relationship between neural activity and TC branch formation, the dynamics of axonal branching was analyzed under various pharmacological treatments. Chronic blockade of firing or synaptic activity reduced the remodeling process, in particular, branch addition in the target layer. However, extension of branches was not affected by this treatment. Together, these findings suggest that neural activity can modify the molecular mechanisms that regulate lamina-specific TC axon branching.}, Author = {Uesaka, Naofumi and Hayano, Yasufumi and Yamada, Akito and Yamamoto, Nobuhiko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;10 Development;21 Neurophysiology;10 circuit formation;21 Activity-development;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8102140}, Number = {19}, Organization = {Neuroscience Laboratories, Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.}, Pages = {5215-23}, Pii = {27/19/5215}, Pubmed = {17494708}, Title = {Interplay between laminar specificity and activity-dependent mechanisms of thalamocortical axon branching}, Uuid = {16BB8A78-9E30-4B3A-9259-3F786944FE61}, Volume = {27}, Year = {2007}, url = {papers/Uesaka_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4685-06.2007}} @article{Ueyama:2004, Abstract = {Protein kinase C (PKC) plays a prominent role in immune signaling. To elucidate the signal transduction in a respiratory burst and isoform-specific function of PKC during FcgammaR-mediated phagocytosis, we used live, digital fluorescence imaging of mouse microglial cells expressing GFP-tagged molecules. betaI PKC, epsilonPKC, and diacylglycerol kinase (DGK) beta dynamically and transiently accumulated around IgG-opsonized beads (BIgG). Moreover, the accumulation of p47(phox), an essential cytosolic component of NADPH oxidase and a substrate for betaI PKC, at the phagosomal cup/phagosome was apparent during BIgG ingestion. Superoxide (O(2)(-)) production was profoundly inhibited by G{\"o}6976, a cPKC inhibitor, and dramatically increased by the DGK inhibitor, R59949. Ultrastructural analysis revealed that BIgG induced O(2)(-) production at the phagosome but not at the intracellular granules. We conclude that activation/accumulation of betaI PKC is involved in O(2)(-) production, and that O(2)(-) production is primarily initiated at the phagosomal cup/phagosome. This study also suggests that DGKbeta plays a prominent role in regulation of O(2)(-) production during FcgammaR-mediated phagocytosis.}, Author = {Ueyama, Takehiko and Lennartz, Michelle R. and Noda, Yukiko and Kobayashi, Toshihiro and Shirai, Yasuhito and Rikitake, Kyoko and Yamasaki, Tomoko and Hayashi, Shigeto and Sakai, Norio and Seguchi, Harumichi and Sawada, Makoto and Sumimoto, Hideki and Saito, Naoaki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {Phagocytosis;Protein Kinase C;Oxidants;Animals;Humans;Comparative Study;Cell Line, Transformed;Microglia;Superoxides;11 Glia;Phagocytes;Green Fluorescent Proteins;Microspheres;Phagosomes;Mice;Receptors, IgG;Isoenzymes;Luminescent Proteins;Diacylglycerol Kinase;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {2985117R}, Number = {7}, Organization = {Laboratory of Molecular Pharmacology, Biosignal Research Center, Kobe University, Kobe, Japan.}, Pages = {4582-9}, Pii = {173/7/4582}, Pubmed = {15383592}, Title = {Superoxide production at phagosomal cup/phagosome through beta I protein kinase C during Fc gamma R-mediated phagocytosis in microglia}, Uuid = {C3AE759E-D686-490F-91D0-A8E8173E9BA4}, Volume = {173}, Year = {2004}} @article{Uhlhaas:2006, Abstract = {Following the discovery of context-dependent synchronization of oscillatory neuronal responses in the visual system, novel methods of time series analysis have been developed for the examination of task- and performance-related oscillatory activity and its synchronization. Studies employing these advanced techniques revealed that synchronization of oscillatory responses in the beta- and gamma-band is involved in a variety of cognitive functions, such as perceptual grouping, attention-dependent stimulus selection, routing of signals across distributed cortical networks, sensory-motor integration, working memory, and perceptual awareness. Here, we review evidence that certain brain disorders, such as schizophrenia, epilepsy, autism, Alzheimer's disease, and Parkinson's are associated with abnormal neural synchronization. The data suggest close correlations between abnormalities in neuronal synchronization and cognitive dysfunctions, emphasizing the importance of temporal coordination. Thus, focused search for abnormalities in temporal patterning may be of considerable clinical relevance.}, Author = {Uhlhaas, Peter J. and Singer, Wolf}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Epilepsy;Brain Diseases;10 Development;research support, non-u.s. gov't;Cognition Disorders;Alzheimer Disease;Autistic Disorder;Brain Mapping;Parkinson Disease;Cortical Synchronization;Animals;Humans;10 genetics malformation;review;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Neurophysiology, Max Planck Institute for Brain Research, Deutschordenstrasse 46, Frankfurt am Main, 60528, Germany. uhlhaas\@mpih-frankfurt.mpg.de}, Pages = {155-68}, Pii = {S0896-6273(06)00727-6}, Pubmed = {17015233}, Title = {Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology}, Uuid = {451712CD-A15D-4110-95A5-91BEF2AD3371}, Volume = {52}, Year = {2006}, url = {papers/Uhlhaas_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.09.020}} @article{Ule:2005, Abstract = {Alternative RNA splicing greatly increases proteome diversity and may thereby contribute to tissue-specific functions. We carried out genome-wide quantitative analysis of alternative splicing using a custom Affymetrix microarray to assess the role of the neuronal splicing factor Nova in the brain. We used a stringent algorithm to identify 591 exons that were differentially spliced in the brain relative to immune tissues, and 6.6\%of these showed major splicing defects in the neocortex of Nova2-/- mice. We tested 49 exons with the largest predicted Nova-dependent splicing changes and validated all 49 by RT-PCR. We analyzed the encoded proteins and found that all those with defined brain functions acted in the synapse (34 of 40, including neurotransmitter receptors, cation channels, adhesion and scaffold proteins) or in axon guidance (8 of 40). Moreover, of the 35 proteins with known interaction partners, 74\%(26) interact with each other. Validating a large set of Nova RNA targets has led us to identify a multi-tiered network in which Nova regulates the exon content of RNAs encoding proteins that interact in the synapse.}, Author = {Ule, Jernej and Ule, Aljaz and Spencer, Joanna and Williams, Alan and Hu, Jing-Shan S. and Cline, Melissa and Wang, Hui and Clark, Tyson and Fraser, Claire and Ruggiu, Matteo and Zeeberg, Barry R. and Kane, David and Weinstein, John N. and Blume, John and Darnell, Robert B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Antigens, Neoplasm;Synapses;10 Development;Mice, Knockout;Research Support, Non-U.S. Gov't;Nerve Tissue Proteins;Alternative Splicing;Research Support, U.S. Gov't, P.H.S.;Neocortex;Oligonucleotide Array Sequence Analysis;Research Support, N.I.H., Extramural;RNA-Binding Proteins;Animals;Mice;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {9216904}, Number = {8}, Organization = {Howard Hughes Medical Institute and Laboratory of Molecular Neuro-Oncology, The Rockefeller University, New York, New York, USA.}, Pages = {844-52}, Pii = {ng1610}, Pubmed = {16041372}, Title = {Nova regulates brain-specific splicing to shape the synapse}, Uuid = {B45FE5B2-123E-4E77-8AFC-466C0FFA3363}, Volume = {37}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ng1610}} @article{Ulfig:2004, Abstract = {Whereas several studies have addressed the activation of microglia (the resident mononuclear phagocytes of the brain) and macrophages within the nervous system in experimental animal models of congenital and induced hydrocephalus, little is known of their state of activation or regional distribution in human fetal hydrocephalus. This investigation aimed to address such questions. Ten human fetal cases [20-36 gestational weeks (GW) at postmortem] previously diagnosed with hydrocephalus on ultrasound examination in utero, and 10 non-hydrocephalic controls (22-38 GW at postmortem) were assessed immufcnohistochemically with antibodies directed against MHC class II and CD68 antigens, and lectin histochemistry with Lycopersicon esculentum (tomato lectin). Adjacent sections were also immunoreacted with an antiserum to laminin to detect cerebral blood vessels. Eight out of the 10 hydrocephalus cases showed numerous CD68 and tomato lectin-positive macrophages located at focal regions along the ependymal lining of the lateral ventricles (particularly within the occipital horn). However, only five of these cases demonstrated MHC class II positive macrophages associated with the ventricular lining. Microglial reactivity within periventricular regions could also be identified using the lectin in four cases, two of which were also immunoreactive with CD68 (but not with MHC class II). By comparison, in control cases five out of 10 fetal brains (aged between 20 and 24 GW) showed few or no ependymal or supraependymal macrophages. One case at 28 GW, and cases at 32 and 38 GW (two of which were diagnosed with intrauterine hypoxic-ischemia) did, however, show some MHC class II (CD68 negative) cells located at the ependymal surface. Nevertheless, these were not as numerous or intensely immunoreactive as in the hydrocephalus cases. Microglia interspersed throughout the intermediate zone and circumscribing the basal ganglia were within normal confines in all cases examined. Hydrocephalic cases additionally showed focal regions of hypovascularization or alterations in the structure and orientation of capillaries within periventricular areas, compared to controls. The macrophage response detected at the ependymal lining of the ventricles and within the periventricular area in hydrocephalus may be related both to the severity of hydrocephalus and the age of the fetus.}, Author = {Ulfig, Norbert and Bohl, J{\"u}rgen and Neud{\"o}rfer, Frank and Rezaie, Payam}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0387-7604}, Journal = {Brain Dev}, Keywords = {Pregnancy;Plant Lectins;case reports;Antigens, Differentiation, Myelomonocytic;Macrophages;Humans;Brain;Microglia;Female;Antigens, CD;Hydrocephalus;Cerebrovascular Circulation;11 Glia;Laminin;Male;Cause of Death;Genes, MHC Class II;Adult;Immunohistochemistry;Gestational Age;Fetal Diseases}, Month = {8}, Nlm_Id = {7909235}, Number = {5}, Organization = {Neuroembryonic Research Laboratory, Institute of Anatomy, University of Rostock, Gertrudenstrasse 9, D-18055 Rostock, Germany. norbert.ulfig\@med.uni-rostock.de}, Pages = {307-15}, Pii = {S0387760403001724}, Pubmed = {15165671}, Title = {Brain macrophages and microglia in human fetal hydrocephalus}, Uuid = {CC6C46C7-FEBE-41D3-88C6-327087194652}, Volume = {26}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/S0387-7604(03)00172-4}} @article{Umeda:1996, Abstract = {The development of macrophage populations in osteopetrosis (op) mutant mice defective in production of functional macrophage colony-stimulating factor (M-CSF) and the response of these cell populations to exogenous M-CSF were used to classify macrophages into four groups: 1) monocytes, monocyte-derived macrophages, and osteoclasts, 2) MOMA-1-positive macrophages, 3) ER-TR9-positive macrophages, and 4) immature tissue macrophages. Monocytes, monocyte-derived macrophages, osteoclasts in bone, microglia in brain, synovial A cells, and MOMA-1- or ER-TR9-positive macrophages were deficient in op/op mice. The former three populations expanded to normal levels in op/op mice after daily M-CSF administration, indicating that they are developed and differentiated due to the effect of M-CSF supplied humorally. In contrast, the other cells did not respond or very slightly responded to M-CSF, and their development seems due to either M-CSF produced in situ or expression of receptor for M-CSF. Macrophages present in tissues of the mutant mice were immature and appear to be regulated by either granulocyte/macrophage colony-stimulating factor and/or interleukin-3 produced in situ or receptor expression. Northern blot analysis revealed different expressions of GM-CSF and IL-3 mRNA in various tissues of the op/op mice. However, granulocyte/macrophage colony-stimulating factor and interleukin-3 in serum were not detected by enzyme-linked immunosorbent assay. The immature macrophages differentiated and matured into resident macrophages after M-CSF administration, and some of these cells proliferated in response to M-CSF.}, Author = {Umeda, S. and Takahashi, K. and Shultz, L. D. and Naito, M. and Takagi, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Animals;Monocytes;Osteopetrosis;Mice, Mutant Strains;Macrophages;Antigens, Differentiation;Cell Count;Interleukin-3;Liver;Mice, Inbred C57BL;11 Glia;RNA, Messenger;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Blotting, Northern;Antibodies, Monoclonal;Flow Cytometry;Macrophage Colony-Stimulating Factor;Mice;Microscopy, Electron;Stem Cells;Immunohistochemistry;Spleen;Research Support, Non-U.S. Gov't}, Medline = {96312859}, Month = {8}, Nlm_Id = {0370502}, Number = {2}, Organization = {Second Department of Pathology, Kumamoto University School of Medicine, Japan.}, Pages = {559-74}, Pubmed = {8701995}, Title = {Effects of macrophage colony-stimulating factor on macrophages and their related cell populations in the osteopetrosis mouse defective in production of functional macrophage colony-stimulating factor protein}, Uuid = {EB9BA219-003D-43B3-B2AA-33648C1FABF7}, Volume = {149}, Year = {1996}} @article{Unal-Cevik:2004, Abstract = {NeuN immunoreactivity is used as a specific marker for neurons. The number of NeuN-positive cells decreases under pathological conditions. This finding is usually considered as an evidence of neuronal loss. However, decrease in NeuN labeling may also be caused by depletion of the protein or loss of its antigenicity. Hence, we have investigated the morphological features of neurons that lost NeuN immunoreactivity and the NeuN protein levels in mouse brain after cerebral ischemia. The number of NeuN-labeled cells was decreased 6 h after a mild ischemic insult (30 min middle cerebral artery occlusion) in penumbral and core regions. Hematoxylin and eosin (H&E) staining of adjacent sections showed that neurons in the penumbra were not disintegrated but displayed early ischemic changes. The nuclear NeuN staining was dramatically reduced or lost in some neurons. However, Hoechst 33258 staining of the same sections revealed that these nuclei were preserved with an intact membrane. Labeling of neurons that had lost NeuN-positivity with antibodies against caspase-3-p20, which is constitutively not present but emerges in neurons after ischemia, disclosed that these neurons still preserved their integrity. Moreover, Western blots showed that NeuN protein levels were not decreased, suggesting that reduced NeuN antigenicity accounted for loss of immunoreactivity in this mild brain injury model. Supporting this idea, NeuN labeling was partially restored after antigenic retrieval. In conclusion, since NeuN immunoreactivity readily decreases after metabolic perturbations, reduced NeuN labeling should not be taken as an indicator of neuronal loss and, quantitative analysis based on NeuN-positivity should be used cautiously after central nervous system (CNS) injury.}, Author = {Unal-Cevik, Isin and Kilin\c{c}, M{\"u}nire and G{\"u}rsoy-Ozdemir, Yasemin and Gurer, Gunfer and Dalkara, Turgay}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Brain Chemistry;01 Adult neurogenesis general;Brain Ischemia;Comparative Study;Immunohistochemistry;Nerve Tissue Proteins;Biological Markers;evaluation studies;Antigens, Nuclear;Nuclear Proteins;Cell Death;Animals;Brain;Support, Non-U.S. Gov't;Neurons;Mice}, Month = {7}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Institute of Neurological Sciences and Psychiatry, and Faculty of Medicine, Department of Neurology, Hacettepe University, Sihhiye Ankara 06100, Turkey.}, Pages = {169-74}, Pii = {S000689930400616X}, Pubmed = {15223381}, Title = {Loss of NeuN immunoreactivity after cerebral ischemia does not indicate neuronal cell loss: a cautionary note}, Uuid = {5AC49152-D378-11D9-A0E9-000D9346EC2A}, Volume = {1015}, Year = {2004}, url = {papers/Unal-Cevik_BrainRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainres.2004.04.032}} @article{Unger:1993, Abstract = {In five female bone marrow transplant (BMT) recipients of sex-mismatched donor marrow, Y-chromosome specific in situ hybridization was performed on formalin-fixed, paraffin-embedded sections of the medulla to detect the male donor marrow-derived cells. Y-chromosome-bearing cells (Y-cells), thereby donor-derived, were matched with leukocyte common antigen (LCA)-reactive cells in adjacent sections immunostained with anti-LCA antibody. Y-cells included mononuclear leukocytes (MNL) within the vessel lumen and infiltrating the perivascular space and parenchyma, and "perivascular cells." We have, therefore, concluded that donor marrow-derived MNL, though limited in number, do enter the normal-appearing brain and can transform to "perivascular cells" in human BMT recipients. It remains, however, to be confirmed whether MNL entering the normal adult CNS parenchyma transform to ramified microglia.}, Author = {Unger, E. R. and Sung, J. H. and Manivel, J. C. and Chenggis, M. L. and Blazar, B. R. and Krivit, W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Adolescent;Colorimetry;Antigens, CD45;Follow-Up Studies;Child, Preschool;Humans;Bone Marrow Transplantation;Brain;Female;Child;Sex Factors;11 Glia;Polymorphism, Restriction Fragment Length;Male;Aged;In Situ Hybridization;Research Support, U.S. Gov't, P.H.S.;Adult;Y Chromosome;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {93367517}, Month = {9}, Nlm_Id = {2985192R}, Number = {5}, Organization = {Department of Pathology, Emory University, Atlanta, Georgia.}, Pages = {460-70}, Pubmed = {8103085}, Title = {Male donor-derived cells in the brains of female sex-mismatched bone marrow transplant recipients: a Y-chromosome specific in situ hybridization study}, Uuid = {5F287E74-851E-4885-8432-FB73DFED1564}, Volume = {52}, Year = {1993}} @article{Upender:1999, Abstract = {Neuronal elimination in the developing CNS is accomplished by an orderly type of cellular suicide called programmed cell death. The principal non-neuronal cells implicated in regulating programmed cell death and subsequent phagocytosis of dying neurons are the brain's macrophage population, the microglia. Little is known about the signaling between microglia and neurons during programmed cell death. However, macrophages in non-neural tissues express receptors for immunoglobulin (IgG) and complement, and these molecules help regulate phagocytosis of dying cells and foreign organisms. Since many of the neurons generated early in CNS development are transient cell types that are immunoreactive for IgG [Upender et al.: J Comp Neurol 1997; 384:271-282], we hypothesized that IgG might alter the phagocytic properties of microglia within the developing nervous system and potentiate engulfment of dying cells. To begin to address this hypothesis, we first asked whether cortical neurons immunoreactive for IgG or calbindin-D28k exhibit morphological evidence of programmed cell death in the cerebral cortex of neonatal rat pups. Secondly, we quantified the incidence of contacts made by microglia on IgG- vs. calbindin-immunoreactive neurons. Thirdly, perturbation experiments were performed to elevate intracortical levels of IgG and the incidence of microglia:neuron contacts were determined. We found that although the nuclei of some IgG-immunoreactive neurons exhibited condensation and fragmentation characteristic of programmed cell death, we did not observe pyknotic calbindin-immunoreactive neurons. IgG-immunoreactive neurons were also more likely to be contacted by microglia than calbindin-immunoreactive neurons. Elevating intracortical levels of IgG experimentally led to a dramatic increase in the expression of microglia complement receptors throughout the cerebral cortex. Taken together, these results suggest that IgG normally present within neuronal subsets in the developing cerebral cortex could serve to locally regulate the expression of complement receptors on microglia.}, Author = {Upender, M. B. and Naegele, J. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Phagocytosis;Rats, Long-Evans;Animals;Up-Regulation;Rats;Immunoglobulin G;Immunity, Maternally-Acquired;Apoptosis;Female;Cell Communication;Microglia;Not relevant;Calcium-Binding Protein, Vitamin D-Dependent;11 Glia;Male;Receptors, Complement;Membrane Glycoproteins;Cerebral Cortex;Neurons;Support, U.S. Gov't, Non-P.H.S.}, Medline = {20108839}, Nlm_Id = {7809375}, Number = {6}, Organization = {Biology Department and Program in Neuroscience and Behavior, Wesleyan University, Middletown, CT, USA.}, Pages = {491-505}, Pii = {dne21491}, Pubmed = {10640867}, Title = {Activation of microglia during developmentally regulated cell death in the cerebral cortex}, Uuid = {7EC8699F-EE25-11DA-8605-000D9346EC2A}, Volume = {21}, Year = {1999}, url = {papers/Upender_DevNeurosci1999.pdf}} @article{Uziel:2006, Abstract = {The complex task of wiring up the brain during embryonic development is achieved by a multitude of guidance signals acting in complex combinations to drive growing axons to their proper targets. The somatosensory system provides an extensively studied model system featuring many universal mechanisms of neural development. In rodents, it constitutes an important model to study how precise topographic connections are achieved. Recent evidence suggests that the Eph/ephrin family of guidance molecules is of pivotal importance for the development of the somatosensory system. Members of Eph/ephrin family are thought to be involved in the global presorting of thalamic axons projecting to the cortex, in labeling specific cortical areas for innervation, in providing topographic cues within the target area, and in distinguishing cortical layers for intracortical wiring. The Eph/ephrin system also seems to contribute to the formation of specific corticothalamic feedback projections. So far, the functions of only a few members of the Eph/ephrin family have been examined, but expression analysis indicates complex combinatorial effects of these signaling molecules. Understanding the Eph/ephrin wiring code is expected to yield new insights into the development and plasticity of brain circuits involved in higher functions.}, Author = {Uziel, Daniela and Garcez, Patricia and Lent, Roberto and Peuckert, Christiane and Niehage, Ronny and Weth, Franco and Bolz, J{\"u}rgen}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1552-4884}, Journal = {Anat Rec A Discov Mol Cell Evol Biol}, Keywords = {24 Pubmed search results 2008;10 Development;research support, non-u.s. gov't;Neural Pathways;10 circuit formation;Ephrins;Somatosensory Cortex;Animals;Humans;Thalamus;review;Axons}, Month = {2}, Nlm_Id = {101234285}, Number = {2}, Organization = {Departamento de Anatomia, Instituto de Ci\^{e}ncias Biom{\'e}dicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. daniuzi\@anato.ufrj.br}, Pages = {135-42}, Pubmed = {16411249}, Title = {Connecting thalamus and cortex: the role of ephrins}, Uuid = {EF502DD8-4B6C-48E9-A187-83F2A6B86C6F}, Volume = {288}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ar.a.20286}} @article{Vaillant:1999, Abstract = {In this report, we have examined the mechanisms whereby neurotrophins and neural activity coordinately regulate neuronal survival, focussing on sympathetic neurons, which require target-derived NGF and neural activity for survival during development. When sympathetic neurons were maintained in suboptimal concentrations of NGF, coincident depolarization with concentrations of KCl that on their own had no survival effect, synergistically enhanced survival. Biochemical analysis revealed that depolarization was sufficient to activate a Ras-phosphatidylinositol 3-kinase-Akt pathway (Ras-PI3-kinase-Akt), and function-blocking experiments using recombinant adenovirus indicated that this pathway was essential for approximately 50\%of depolarization-mediated neuronal survival. At concentrations of NGF and KCl that promoted synergistic survival, these two stimuli converged to promote increased PI3-kinase-dependent Akt phosphorylation. This convergent PI3-kinase-Akt pathway was essential for synergistic survival. In contrast, inhibition of calcium/calmodulin-dependent protein kinase II revealed that, while this molecule was essential for depolarization-induced survival, it had no role in KCl- induced Akt phosphorylation, nor was it important for synergistic survival by NGF and KCl. Thus, NGF and depolarization together mediate survival of sympathetic neurons via intracellular convergence on a Ras-PI3-kinase-Akt pathway. This convergent regulation of Akt may provide a general mechanism for coordinating the effects of growth factors and neural activity on neuronal survival throughout the nervous system. 0021-9525 Journal Article}, Author = {Vaillant, A. R. and Mazzoni, I. and Tudan, C. and Boudreau, M. and Kaplan, D. R. and Miller, F. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Cell Biol}, Keywords = {Protein-Tyrosine Kinase/antagonists &inhibitors/metabolism;Potassium Chloride/pharmacology;Drug Synergism;Neurons/*cytology/drug effects/enzymology;Membrane Potentials/drug effects/physiology;Receptor, trkA;Rats;Proto-Oncogene Proteins/antagonists &inhibitors/*metabolism/physiology;Cells, Cultured;Apoptosis/drug effects;Receptor Protein-Tyrosine Kinases/antagonists &inhibitors/physiology;Animals;Nerve Growth Factors/*pharmacology;Sympathetic Nervous System/cytology;Cell Survival/drug effects;C abstr;Rats, Sprague-Dawley;Enzyme Activation/drug effects;Ca(2+)-Calmodulin Dependent Protein Kinase/antagonists &;Animals, Newborn;inhibitors/metabolism;Receptors, Nerve Growth Factor/antagonists &inhibitors/physiology;Phosphorylation/drug effects;Protein-Serine-Threonine Kinases/antagonists &inhibitors/metabolism;04 Adult neurogenesis factors;1-Phosphatidylinositol 3-Kinase/antagonists &inhibitors/*metabolism;Proto-Oncogene Protein p21(ras)/metabolism;Mitogen-Activated Protein Kinase Kinases;Signal Transduction/*drug effects}, Number = {5}, Organization = {Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada H3A 2B4.}, Pages = {955-66}, Pubmed = {10477751}, Title = {Depolarization and neurotrophins converge on the phosphatidylinositol 3-kinase-Akt pathway to synergistically regulate neuronal survival}, Uuid = {15095E6A-C86D-4D95-B5AE-E72D75BCE5A3}, Volume = {146}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10477751}} @article{Vallieres:2002, Abstract = {Postnatal neurogenesis can be modulated after brain injury, but the role of the attendant expression of inflammatory mediators in such responses remains to be determined. Here we report that transgenically directed production of interleukin-6 (IL-6) by astroglia decreased overall neurogenesis by 63\%in the hippocampal dentate gyrus of young adult transgenic mice. The proliferation, survival, and differentiation of neural progenitor cells labeled with the thymidine analog bromodeoxyuridine were all reduced in the granule cell layer of these mice, whereas their distribution and gliogenesis appeared normal. These effects were not a consequence of general toxicity of the IL-6 transgene, because they were manifested in the absence of neuronal death and of major changes in glial cell number and morphology. These findings suggest that long-term exposure of the brain to proinflammatory mediators such as IL-6, as is seen in certain degenerative disorders and infections, can interfere with adult neurogenesis.}, Author = {Vallieres, L. and Campbell, I. L. and Gage, F. H. and Sawchenko, P. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Neurosci}, Keywords = {Fluorescent Dyes;Cell Differentiation/genetics;Phenotype;Animal;Cell Count;Mice, Transgenic;Hippocampus/cytology/*metabolism;Cell Survival/genetics;Astrocytes/cytology/*metabolism;Support, Non-U.S. Gov't;Cell Division/genetics;*Neurons/cytology;C;04 Adult neurogenesis factors;Interleukin-6/*biosynthesis/genetics;Support, U.S. Gov't, P.H.S.;Mice;Dentate Gyrus/cytology/metabolism;Immunohistochemistry;Genes, Reporter;Gene Expression;Bromodeoxyuridine;Transgenes}, Number = {2}, Organization = {Laboratories of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {486-92.}, Title = {Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6}, Uuid = {759FAA48-64F3-4659-9D50-36C9B6058CE6}, Volume = {22}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11784794%20http://www.jneurosci.org/cgi/content/full/22/2/486%20http://www.jneurosci.org/cgi/content/abstract/22/2/486}} @article{Vallieres:2003, Abstract = {Cytogenesis in the adult brain can result from the recruitment of circulating precursors, but the proposal that some such cells transdifferentiate into neural elements is controversial. We have reinvestigated this issue by following the phenotypic fate of bone marrow cells expressing the green fluorescent protein transplanted into the systemic circulation of irradiated mice. Thousands of donor-derived cells were detected throughout brains of recipients killed 1-12 months after transplantation, but none displayed neuronal, macroglial, or endothelial characteristics, even after injury. Among those that crossed the endothelium of the cerebral cortex, >99.7\%were identified as perivascular macrophages. Newly formed parenchymal microglia were found in significant numbers only in the cerebellum and at injury sites. Therefore, bone marrow does supply the mature brain with new specialized cells; however, mesenchymal precursors neither adopt neural phenotypes nor contribute to cerebral vascular remodeling. This continuous traffic of macrophages across the blood-brain barrier provides a vehicle to introduce therapeutic genes into the nervous system.}, Author = {Valli\`{e}res, Luc and Sawchenko, Paul E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Animals;Macrophages;Bone Marrow Transplantation;Phenotype;Brain;Microglia;Cell Count;Mice, Transgenic;Mice, Inbred C57BL;Male;Blood-Brain Barrier;Time;Bone Marrow Cells;Brain Injuries;Cell Lineage;Hematopoietic System;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Mice;Cell Division;Genes, Reporter;Cerebral Decortication;Luminescent Proteins}, Medline = {22716544}, Month = {6}, Nlm_Id = {8102140}, Number = {12}, Organization = {Laboratoire d'Endocrinologie Mol{\'e}culaire, Centre de Recherche du Centre Hospitalier de l'Universit{\'e} Laval, Universit{\'e} Laval, Qu{\'e}bec, Qu{\'e}bec, G1V 4G2, Canada. Luc.Vallieres\@crchul.ulaval.ca}, Pages = {5197-207}, Pii = {23/12/5197}, Pubmed = {12832544}, Title = {Bone marrow-derived cells that populate the adult mouse brain preserve their hematopoietic identity}, Uuid = {8481E025-D3B7-11D9-A0E9-000D9346EC2A}, Volume = {23}, Year = {2003}} @article{Van-De-Bor:2002, Abstract = {Neurons and glial cells depend on similar developmental pathways and often originate from common precursors; however, the differentiation of one or the other cell type depends on the activation of cell-specific pathways. In Drosophila, the differentiation of glial cells depends on a transcription factor, Glide/Gcm. This glial-promoting factor is both necessary and sufficient to induce the central and peripheral glial fates at the expense of the neuronal fate. In a screen for mutations affecting the adult peripheral nervous system, we have found a dominant mutation inducing supernumerary sensory organs. Surprisingly, this mutation is allelic to glide/gcm and induces precocious glide/gcm expression, which, in turn, activates the proneural genes. As a consequence, sensory organs are induced. Thus, temporal misregulation of the Glide/Gcm glial-promoting factor reveals a novel potential for this cell fate determinant. At the molecular level, this implies unpredicted features of the glide/gcm pathway. These findings also emphasize the requirement for both spatial and temporal glide/gcm regulation to achieve proper cell specification within the nervous system.}, Author = {Van De Bor, V. and Heitzler, P. and Leger, S. and Plessy, C. and Giangrande, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Genetics}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {3}, Organization = {Institut de Genetique et Biologie Moleculaire et Cellulaire IGBMC/CNRS/ULP/INSERM-BP 163 67404 Illkirch, c.u. de Strasbourg, France.}, Pages = {1095-106.}, Title = {Precocious expression of the glide/gcm glial-promoting factor in Drosophila induces neurogenesis}, Uuid = {3EC4E8BE-EB75-4BE3-9982-2F1A529E9429}, Volume = {160}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11901125%20http://www.genetics.org/cgi/content/full/160/3/1095%20http://www.genetics.org/cgi/content/abstract/160/3/1095}} @article{Van-Hoeven:2005, Abstract = {BACKGROUND: Retrovirus infection depends on binding of the retroviral envelope (Env) protein to specific cell-surface protein receptors. Interference, or superinfection resistance, is a frequent consequence of retroviral infection, and occurs when newly-synthesized Env binds to receptor proteins resulting in a block to entry by retroviruses that use the same receptors. Three groups of viruses demonstrate a non-reciprocal pattern of interference (NRI), which requires the existence of both a common receptor utilized by all viruses within the group, and a specific receptor that is used by a subset of viruses. In the case of amphotropic and 10A1 murine leukemia viruses (MLV), the common and specific receptors are the products of two related genes. In the case of avian sarcoma and leukosis virus types B, D, and E, the two receptors are distinct protein products of a single gene. NRI also occurs between xenotropic and polytropic MLV. The common receptor, Xpr1, has been identified, but a specific receptor has yet to be described. RESULTS: Using chimeric receptor proteins and interference studies, we have identified a region of Xpr1 that is uniquely utilized by xenotropic MLV and show that this receptor domain is required for non-reciprocal interference. CONCLUSION: We propose a novel pattern of receptor usage by xenotropic and polytropic MLV to explain the NRI observed between these viruses. We propose that the specific and common receptor determinants for xenotropic and polytropic viruses are simultaneously present in discreet domains of a single Xpr1 protein.}, Author = {Van Hoeven, Neal S. and Miller, A. Dusty}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1742-4690}, Journal = {Retrovirology}, Keywords = {15 PS VSVG receptor;15 Retrovirus mechanism;24 Pubmed search results 2008}, Nlm_Id = {101216893}, Number = {1}, Organization = {Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. nvanhoeven\@cdc.gov}, Pages = {76}, Pii = {1742-4690-2-76}, Pubmed = {16354307}, Title = {Use of different but overlapping determinants in a retrovirus receptor accounts for non-reciprocal interference between xenotropic and polytropic murine leukemia viruses}, Uuid = {4655D5C7-9073-4FE7-827D-935AD2507FC1}, Volume = {2}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1186/1742-4690-2-76}} @article{Van-Kampen:2004, Abstract = {Abstract Discrete regions of the adult CNS, including the subventricular zone (SVZ), do retain the capacity for neurogenesis. These progenitor cells may represent a potential new source of cells for replacement therapies in neuroregenerative diseases. An understanding of the microenvironmental signals regulating neurogenesis in the adult brain would facilitate the development of such therapeutic approaches. A particularly strong expression of dopamine D(3) receptor mRNA occurs in the proliferative SVZ during prenatal and early postnatal ontogeny. Although its expression diminishes following development, a restricted D(3) receptor expression persists in this region through adulthood, coincident with continued proliferation in this region. Here, we demonstrate a two-fold induction of cell proliferation (BrdU incorporation) in the SVZ and rostral migratory stream of the adult Sprague-Dawley rat brain following intrasubventricular administration of the dopamine D(3) receptor agonist, 7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) for 2 weeks. The number of BrdU-positive cells was elevated ten-fold from very low baseline levels in the neighbouring neostriatum, another region known to express D(3) receptors. These striatal BrdU-positive cells appeared within 3 days following intracerebral infusion of 7-OH-DPAT and were distributed homogeneously throughout the striatum following systemic administration. This suggests that these cells originate from resident progenitor cells rather than the SVZ. Dopamine D(3) receptor activation may serve as a proneuronal differentiation signal as 60-70\%of the new cells had neuronal markers following 7-OH-DPAT infusion. These results suggest that the dopamine D(3) receptor may be a good drug target for cell replacement strategies, particularly because of the fact that its expression is almost exclusively limited to the nervous system. 0953-816x Journal Article}, Author = {Van Kampen, J. M. and Hagg, T. and Robertson, H. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Eur J Neurosci}, Keywords = {01 Adult neurogenesis general;A, C, D pdf}, Number = {9}, Organization = {Department Pharmacology, Dalhousie University, Tupper Building, 5850 College St., Halifax, Nova Scotia, B3H 15X Canada.}, Pages = {2377-87}, Title = {Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D receptor stimulation}, Uuid = {EA0E369E-923A-4B68-8913-C62C74BDDB8B}, Volume = {19}, Year = {2004}, url = {papers/VanKampen_EurJNeurosci2004.pdf}} @article{Vanek:1998, Abstract = {Myelin contains potent inhibitors of neurite growth which have been implicated in the failure of long-distance regeneration of nerve fibres within the CNS. These myelin-associated neurite growth inhibitors may also be involved in the stabilization of neural connections by suppressing sprouting and fibre growth. After lesions of the CNS in neonatal animals, extensive rearrangements of the remaining fibre systems have been observed. In the rat, this plasticity of neuronal connections is severely restricted following the first few weeks of postnatal life, coincident with the progression of myelination of the nervous system. A well-studied example of postnatal plasticity is the sprouting of one corticospinal tract (CST) into the denervated half of the spinal cord after unilateral motor cortex or pyramidal lesions. In the hamster and rat, significant CST sprouting is restricted to the first 10 postnatal days. Here we show that very extensive sprouting of corticospinal fibres occurs after deafferentations as late as P21 if myelination is prevented by neonatal X-irradiation in the rat lumbar spinal cord. Sprouted fibres from the intact CST cross the midline and develop large terminal arbors in the denervated spinal cord, suggesting the establishment of synaptic connections. Our results suggest that myelin and its associated neurite growth inhibitors play an important role in the termination of neurite growth permissive periods during postnatal CNS development. Corticospinal sprouting subsequent to lesions early in life, i.e. in the absence of myelin-associated neurite growth inhibitors may explain the frequent occurrence of mirror movements in patients with hemiplegic cerebral palsy.}, Author = {Vanek, P. and Thallmair, M. and Schwab, M. E. and Kapfhammer, J. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Nerve Fibers;Research Support, Non-U.S. Gov't;Rats, Inbred Lew;Neurites;Nerve Regeneration;Rats;Myelin Sheath;Neuronal Plasticity;Denervation;Pyramidal Tracts;Myelin Proteins;Animals, Newborn;Animals;24 Pubmed search results 2008}, Medline = {98424034}, Month = {1}, Nlm_Id = {8918110}, Number = {1}, Organization = {Institut f{\"u}r Hirnforschung, Universit{\"a}t Z{\"u}rich, Switzerland.}, Pages = {45-56}, Pubmed = {9753112}, Title = {Increased lesion-induced sprouting of corticospinal fibres in the myelin-free rat spinal cord}, Uuid = {FFB42372-63A0-4B34-B99F-02D8BD9713CA}, Volume = {10}, Year = {1998}} @article{Varki:2006, Abstract = {The remarkable structural diversity of glycans in nature, and their roles in cellular processes, host-pathogen interactions, biological diversity and speciation can be explained by evolutionary processes.}, Author = {Varki, Ajit}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {24 Pubmed search results 2008;Glycosyltransferases;Membrane Glycoproteins;Protein Transport;Glycosylation;Gene Expression Regulation, Enzymologic;09 Evolutionary dynamics;Evolution, Molecular;Genetic Speciation;Glycoproteins;Animals;Humans;Orthomyxoviridae;Polysaccharides;Protein Processing, Post-Translational}, Month = {9}, Nlm_Id = {0413066}, Number = {5}, Organization = {Glycobiology Research and Training Center, Departments of Medicine and Cellular & Molecular Medicine, University of California at San Diego, La Jolla, CA 92093, USA. a1varki\@ucsd.edu}, Pages = {841-5}, Pii = {S0092-8674(06)01089-0}, Pubmed = {16959563}, Title = {Nothing in glycobiology makes sense, except in the light of evolution}, Uuid = {1584ECEC-236C-485E-8BA6-BB00847C5FC5}, Volume = {126}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.08.022}} @article{Vasilyev:2002, Abstract = {The hyperpolarization-activated excitatory current I(h) shapes rhythmic firing and other components of excitability in differentiating neurons, and may thus influence activity-dependent CNS development. We therefore studied developmental changes in I(h) and underlying hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits in pyramidal neurons of neonatal mouse hippocampus using electrophysiological and immunofluorescence approaches. I(h) conductance (at -80 mV) tripled in CA3 neurons and quintupled in CA1 neurons between postnatal day 1 (P1) and P20; parallel changes in membrane area resulted in current density maxima at P5 in CA3 and P10 in CA1. Concurrently, I(h) activation times fell sevenfold in CA3 and 10-fold in CA1. A computational model indicates that a decrease in I(h) activation time will increase the rhythmic firing rate. Two mechanisms contributed to more rapid I(h) activation at P20 in CA3 and CA1 neurons: a fall in the intrinsic time constants of two kinetic components, tau(fast) and tau(slow), to 35-40\%(at -90 mV) of their P1 values, and a preferential increase in fast component amplitude and contribution to I(h) (from approximately 35\%to approximately 74\%of total). HCN1, HCN2, and HCN4 immunoreactivities showed independent temporal and spatial developmental patterns. HCN1 immunoreactivity was low at P1 and P5 and increased by P20. HCN2 immunoreactivity was detected at P1 and increased steadily up to P20. HCN4 immunoreactivity was initially low and showed a small increase by P20. We suggest that developmental increases in I(h) amplitude and activation rate reflect changes in the number and underlying structure of I(h) channels, and that I(h) maturation may shape rhythmic activity important for hippocampal circuit maturation. 1529-2401 Journal Article}, Author = {Vasilyev, D. V. and Barish, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:12:00 -0400}, Journal = {J Neurosci}, Keywords = {13 Olfactory bulb anatomy;Protein Subunits;Electric Stimulation;Pyrimidines/pharmacology;Membrane Potentials/drug effects/physiology;In Vitro;Animals;Hippocampus/cytology/growth &development;Patch-Clamp Techniques;Periodicity;Ion Channels/antagonists &inhibitors/*metabolism;Pyramidal Cells/cytology/drug effects/*metabolism;Support, Non-U.S. Gov't;Support, U.S. Gov't, P.H.S.;Age Factors;I pdf;Cell Differentiation/physiology;Mice}, Number = {20}, Organization = {Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.}, Pages = {8992-9004}, Title = {Postnatal development of the hyperpolarization-activated excitatory current Ih in mouse hippocampal pyramidal neurons}, Uuid = {5C5BE4B9-6BFD-463C-915D-245B00D974CA}, Volume = {22}, Year = {2002}, url = {papers/Vasilyev_JNeurosci2002.pdf}} @article{Vasquez:1997, Abstract = {Previous studies demonstrated that nanomolar concentrations of nocodazole can block cells in mitosis without net microtubule disassembly and resulted in the hypothesis that this block was due to a nocodazole-induced stabilization of microtubules. We tested this hypothesis by examining the effects of nanomolar concentrations of nocodazole on microtubule dynamic instability in interphase cells and in vitro with purified brain tubulin. Newt lung epithelial cell microtubules were visualized by video-enhanced differential interference contrast microscopy and cells were perfused with solutions of nocodazole ranging in concentration from 4 to 400 nM. Microtubules showed a loss of the two-state behavior typical of dynamic instability as evidenced by the addition of a third state where they exhibited little net change in length (a paused state). Nocodazole perfusion also resulted in slower elongation and shortening velocities, increased catastrophe, and an overall decrease in microtubule turnover. Experiments performed on BSC-1 cells that were microinjected with rhodamine-labeled tubulin, incubated in nocodazole for 1 h, and visualized by using low-light-level fluorescence microscopy showed similar results except that nocodazole-treated BSC-1 cells showed a decrease in catastrophe. To gain insight into possible mechanisms responsible for changes in dynamic instability, we examined the effects of 4 nM to 12 microM nocodazole on the assembly of purified tubulin from axoneme seeds. At both microtubule plus and minus ends, perfusion with nocodazole resulted in a dose-dependent decrease in elongation and shortening velocities, increase in pause duration and catastrophe frequency, and decrease in rescue frequency. These effects, which result in an overall decrease in microtubule turnover after nocodazole treatment, suggest that the mitotic block observed is due to a reduction in microtubule dynamic turnover. In addition, the in vitro results are similar to the effects of increasing concentrations of GDP-tubulin (TuD) subunits on microtubule assembly. Given that nocodazole increases tubulin GTPase activity, we propose that nocodazole acts by generating TuD subunits that then alter dynamic instability. 1059-1524 Journal Article}, Author = {Vasquez, R. J. and Howell, B. and Yvon, A. M. and Wadsworth, P. and Cassimeris, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Mol Biol Cell}, Keywords = {Dose-Response Relationship, Drug;Animals;Cells, Cultured;EE, T abstr;Mitotic Spindle Apparatus/*drug effects;Sea Urchins;Swine;08 Aberrant cell cycle;Male;Tubulin/*drug effects;Guanosine Triphosphate/metabolism;Sperm Tail/ultrastructure;Macromolecular Systems;Microtubules/*drug effects;EE, T pdf;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Nocodazole/*administration &dosage;Salamandridae}, Number = {6}, Organization = {Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania 18015, USA.}, Pages = {973-85}, Pubmed = {9201709}, Title = {Nanomolar concentrations of nocodazole alter microtubule dynamic instability in vivo and in vitro}, Uuid = {8F586F86-0A17-475E-BD21-7CF78CECA579}, Volume = {8}, Year = {1997}, url = {papers/Vasquez_MolBiolCell1997.pdf}} @article{Vassilopoulos:2003, Abstract = {Results from several experimental systems suggest that cells from one tissue type can form other tissue types after transplantation. This could be due to the presence of multipotential or several types of adult stem cells in donor tissues, or alternatively, to fusion of donor and recipient cells. In a model of tyrosinaemia type I, mice with mutations in the fumarylacetoacetate hydrolase gene (Fah-/-) regain normal liver function after transplantation of Fah+/+ bone marrow cells, and form regenerating liver nodules with normal histology that express Fah. Here we show that these hepatic nodules contain more mutant than wild-type Fah alleles, and that their hepatocytes express both donor and host genes, consistent with polyploid genome formation by fusion of host and donor cells. Using bone marrow cells marked with integrated foamy virus vectors that express green fluorescent protein, we identify common proviral junctions in hepatic nodules and haematopoietic cells. We also show that the haematopoietic donor genome adopts a more hepatocyte-specific expression profile after cell fusion, as the wild-type Fah gene was activated and the pan-haematopoietic CD45 marker was no longer expressed. 0028-0836 Journal Article}, Author = {Vassilopoulos, G. and Wang, P. R. and Russell, D. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Nature}, Keywords = {Cell Differentiation;Animals;Heterozygote;Liver/cytology/metabolism;Gene Expression Regulation;Hematopoietic Stem Cells/cytology/metabolism;*Liver Regeneration;Hybrid Cells/*cytology/metabolism;DNA/analysis/genetics;Bone Marrow Cells/*cytology/metabolism;Female;EE pdf;Cell Fusion;Gene Deletion;Mice, Inbred C57BL;08 Aberrant cell cycle;Hepatocytes/*cytology/metabolism/*transplantation;Male;Diploidy;Hydrolases/genetics;Support, Non-U.S. Gov't;Homozygote;Organ Specificity;RNA, Messenger/genetics/metabolism;Polyploidy;Mice;*Bone Marrow Transplantation}, Number = {6934}, Organization = {Division of Hematology, University of Washington, Seattle, Washington 98195, USA.}, Pages = {901-4}, Pubmed = {12665833}, Title = {Transplanted bone marrow regenerates liver by cell fusion}, Uuid = {E40348A5-C829-431D-A5D0-B0AAA995A968}, Volume = {422}, Year = {2003}, url = {papers/Vassilopoulos_Nature2003.pdf}} @article{Velling:1985, Abstract = {The action of optical radiation on neocortical bioelectrical activity and on a penicillin-induced epileptic focus was investigated. The direct action of ultraviolet (UV) radiation with wavelengths 280, 310, and 365 nm was shown to increase the amplitude of the spontaneous EEG and to potentiate epileptiform activity, whereas the action of subthreshold radiation with wavelengths of 580 and 630 nm caused a reduction of EEG amplitude and inhibition of epileptiform activity. On the basis of the writers' own results and data in the literature it is postulated that the mechanism of action of UV radiation on neocortical electrical activity is based on changes in permeability of neuronal membranes to Na and K ions and subsequent membrane depolarization, whereas the action of visible radiation leads to thermal injury to the neurons in the irradiated zone, inducing irreversible suppression of their activity and a decrease in amplitude of the EEG.}, Author = {Velling, V. A. and Gal'dinov, G. V. and Gromova, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0097-0549}, Journal = {Neurosci Behav Physiol}, Keywords = {Penicillins;Epilepsy;Ultraviolet Rays;Electroencephalography;21 Neurophysiology;Cats;Comparative Study;Rabbits;Light;Animals;Cerebral Cortex;24 Pubmed search results 2008;21 Epilepsy}, Medline = {85296683}, Nlm_Id = {0330471}, Number = {3}, Pages = {207-13}, Pubmed = {4033917}, Title = {Changes in neocortical function in response to the direct action of optical radiation}, Uuid = {E8CF40B3-DBA3-430F-BCCF-0642F6FE26CB}, Volume = {15}, Year = {1985}} @article{Venter:2004, Abstract = {We have applied "whole-genome shotgun sequencing" to microbial populations collected en masse on tangential flow and impact filters from seawater samples collected from the Sargasso Sea near Bermuda. A total of 1.045 billion base pairs of nonredundant sequence was generated, annotated, and analyzed to elucidate the gene content, diversity, and relative abundance of the organisms within these environmental samples. These data are estimated to derive from at least 1800 genomic species based on sequence relatedness, including 148 previously unknown bacterial phylotypes. We have identified over 1.2 million previously unknown genes represented in these samples, including more than 782 new rhodopsin-like photoreceptors. Variation in species present and stoichiometry suggests substantial oceanic microbial diversity.}, Author = {Venter, J. Craig and Remington, Karin and Heidelberg, John F. and Halpern, Aaron L. and Rusch, Doug and Eisen, Jonathan A. and Wu, Dongying and Paulsen, Ian and Nelson, Karen E. and Nelson, William and Fouts, Derrick E. and Levy, Samuel and Knap, Anthony H. and Lomas, Michael W. and Nealson, Ken and White, Owen and Peterson, Jeremy and Hoffman, Jeff and Parsons, Rachel and Baden-Tillson, Holly and Pfannkoch, Cynthia and Rogers, Yu-Hui H. and Smith, Hamilton O.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Synechococcus Group;Ecosystem;Cyanobacteria;Sequence Analysis, DNA;Seawater;Rhodopsin;Photosynthesis;Atlantic Ocean;Water Microbiology;Phylogeny;Genome, Archaeal;Genomics;Computational Biology;23 Technique;Bacteria;Biodiversity;Genome, Bacterial;Plasmids;Support, Non-U.S. Gov't;Genes, rRNA;Genes, Archaeal;Archaea;Support, U.S. Gov't, Non-P.H.S.;Genes, Bacterial;Molecular Sequence Data;Bacteriophages;Eukaryotic Cells}, Month = {4}, Nlm_Id = {0404511}, Number = {5667}, Organization = {Institute for Biological Energy Alternatives, 1901 Research Boulevard, Rockville, MD 20850, USA. jcventer\@tcag.org}, Pages = {66-74}, Pii = {1093857}, Pubmed = {15001713}, Title = {Environmental genome shotgun sequencing of the Sargasso Sea}, Uuid = {A2FBE27F-4440-43AA-B8DA-F7449CD9CC3D}, Volume = {304}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1093857}} @article{Vercelli:1997, Author = {Vercelli, A. and Assal, F. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:42 -0400}, Issn = {0065-2598}, Journal = {Adv Exp Med Biol}, Keywords = {Neurons;Dendrites;Cats;Pyramidal Cells;Not relevant;11 Glia;review, tutorial;Animals;Support, Non-U.S. Gov't;Visual Pathways;review;Corpus Callosum}, Medline = {98075493}, Nlm_Id = {0121103}, Organization = {Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, I, H\^{o}pital Cantonal Universitaire de Gen\`{e}ve, CH.}, Pages = {145-58}, Pubmed = {9413572}, Title = {Dendritic development of visual callosal neurons}, Uuid = {5E451526-5185-4C46-B3CA-9F99A40D791B}, Volume = {429}, Year = {1997}} @article{Vercelli:2000, Abstract = {Over the last 20 years, the choice of neural tracers has increased manyfold, and includes newly introduced anterograde tracers that allow quantitation of single-axon morphologies, and retrograde tracers that can be combined with intracellular fills for the study of dendritic arbors of neurons which have a specific projection pattern. The combination of several different tracers now permits the comparison of multiple connections in the same animal, both quantitatively and qualitatively. Moreover, the finding of new virus strains, which infect neural cells without killing them, provides a tool for studying multisynaptic connections that participate in a circuit. In this paper, the labeling characteristics, mechanism of transport and advantages/disadvantages of use are discussed for the following recently introduced neural tracers: carbocyanine dyes, fluorescent latex microspheres, fluorescent dextrans, biocytin, dextran amines, Phaseolus vulgaris leucoagglutinin, cholera toxin and viruses. We also suggest the choice of specific tracers, depending on the experimental animal, age and type of connection to be studied, and discuss quantitative methodologies.}, Author = {Vercelli, A. and Repici, M. and Garbossa, D. and Grimaldi, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0361-9230}, Journal = {Brain Res Bull}, Keywords = {Synapses;Central Nervous System;21 Neurophysiology;Axonal Transport;research support, non-u.s. gov't ;Mammals;Humans;Animals;24 Pubmed search results 2008;review}, Month = {1}, Nlm_Id = {7605818}, Number = {1}, Organization = {Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, Italy. alessandro.vercelli\@unito.it}, Pages = {11-28}, Pii = {S0361-9230(99)00229-4}, Pubmed = {10654576}, Title = {Recent techniques for tracing pathways in the central nervous system of developing and adult mammals}, Uuid = {86748694-EB02-4639-B240-44F050586BD4}, Volume = {51}, Year = {2000}, url = {papers/Vercelli_BrainResBull2000.pdf}} @article{Vercelli:2003, Abstract = {The parafascicular nucleus (PFN) of the rat, homologous to the human centre m{\'e}dian, is an intralaminar nucleus of the thalamus, classically considered as part of the ascending activating system. We have previously demonstrated that it is also connected to several subcortical nuclei. To obtain a more detailed picture of the connectivity of the PFN, the organization and the topography of the reciprocal parafascicular-telencephalic relationships were studied in both adult and developing rats, using anterograde and retrograde neuronal tracers. In the adult rat, the ascending parafascicular projections were densest to the striatum, dense to the frontal and least dense to cingulate cortex, and were strictly ipsilateral. They displayed a loose topography, with the more medial parafascicular neurons projecting to the medial frontal and cingulate cortex and medial striatum, and the more lateral neurons projecting to the lateral frontal cortex and lateral striatum. All these connections were already present at embryonic day 19. Parafascicular neurons projecting to the telencephalon in adult rats were mostly of the multipolar type, with a few bipolar neurons. In neonatal rats they showed a bipolar morphology at birth; they became mostly multipolar later on, with an increasing complexity of the dendritic arbor up to postnatal day 10. Neurons in the frontal cortex retrogradely labelled from the PFN were more numerous perinatally, and decreased as early as postnatal day 5. The telencephalic connections of the PFN were found to be more discrete and restricted than previously thought, thus suggesting a more specific functional role for the nucleus than cortical recruitment.}, Author = {Vercelli, Alessandro and Marini, Gabriella and Tredici, Giovanni}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Rats;Neural Pathways;Fluorescent Dyes;Lysine;Rats, Wistar;Microscopy, Fluorescence;Animals;Intralaminar Thalamic Nuclei;24 Pubmed search results 2008;Neurons}, Medline = {22770073}, Month = {7}, Nlm_Id = {8918110}, Number = {2}, Organization = {Department of Anatomy, Pharmacology and Forensic Medicine, University of Torino, corso M. D'Azeglio 52, 10126 Torino, Italy. alessandro.vercelli\@unito.it}, Pages = {275-89}, Pii = {2743}, Pubmed = {12887409}, Title = {Anatomical organization of the telencephalic connections of the parafascicular nucleus in adult and developing rats}, Uuid = {D4B83FDF-C216-4370-9692-6077DC559160}, Volume = {18}, Year = {2003}} @article{Vercelli:2004, Abstract = {The apical dendrites of the pyramidal neurons of the cerebral cortex form radial bundles in all species and areas. Using microtubule-associated protein (MAP)2 immunostaining and Voronoi tessellation analysis in the rat visual cortex, we obtained objective criteria to define dendritic bundles in tangential sections: in supragranular layers of the rat visual cortex we found bundles of 6-6.4 dendrites, at a density of 1929 bundles/mm(2) and a centre-to-centre distance of 27 micro m. Using lipophilic tracers to label different pyramidal cell populations, based on the same criteria as in MAP2-immunostained material, we found that in the rat visual cortex the bundles consist of neurons with specific targets. Neurons projecting to the ipsi- or contralateral cortex form bundles together and with neurons projecting to the striatum, but not with those projecting to the superior colliculus, dorsal division of the lateral geniculate nucleus or through the cerebral peduncle. The latter neurons form bundles with neurons projecting to the striatum. Thus, the cerebral cortex is organized in minicolumns of output neurons visible at the earliest ages studied (P3), which might have a higher probability of being interconnected than those outside.}, Author = {Vercelli, Alessandro E. and Garbossa, Diego and Curtetti, Roberta and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Not relevant;11 Glia}, Month = {7}, Nlm_Id = {8918110}, Number = {2}, Organization = {Department of Anatomy, Pharmacology and Forensic Medicine, corso M. d'Azeglio 52, 10126 Torino, Italy. alessandro.vercelli\@unito.it}, Pages = {495-502}, Pii = {EJN3483}, Pubmed = {15233758}, Title = {Somatodendritic minicolumns of output neurons in the rat visual cortex}, Uuid = {F2876FE2-126A-49DD-B4CE-02C8FC9C596F}, Volume = {20}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1460-9568.2004.03483.x}} @article{Vercelli:1992, Abstract = {Callosally projecting neurons in areas 17 and 18 of the adult cat can be classified into two types on the basis of their dendritic morphology: pyramidal and stellate cells. The latter are nearly exclusively of the spinous type and are predominantly located in upper layer IV. Retrograde transport of the carbocyanine dye DiI, applied to the corpus callosum, showed that, up to P6, all callosally projecting neurons resemble pyramids in the possession of an apical dendrite reaching layer I. At P10, however, callosally projecting neurons with stellate morphology were found. A study was designed to distinguish whether these neurons are late in extending their axons to the corpus callosum or, alternatively, have transient apical dendrites. To this end, callosally projecting neurons were retrogradely labeled by fluorescent beads injected in areas 17 and 18 at P1-P3 and then either relabeled with DiI applied to the corpus callosum at P10 or intracellularly injected with Lucifer Yellow at P57. Double-labeled stellate and pyramidal cells were found in similar proportions to those found for the total, single-labeled population of callosally projecting neurons. It is therefore concluded that callosally projecting spiny stellate cells initially possess an apical dendrite and a pyramidal morphology. At P6, i.e. close to the time when stellate cells appear, layer IV neurons with an atrophic apical dendrite were found, suggestive of an apical dendrite in the process of being eliminated.}, Author = {Vercelli, A. and Assal, F. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Animals;Neural Pathways;Not relevant;11 Glia;Pyramidal Tracts;Microspheres;Animals, Newborn;Histocytochemistry;Support, Non-U.S. Gov't;F, G ;Neurons;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Horseradish Peroxidase;Wheat Germ Agglutinins;Carbocyanines;Corpus Callosum;Visual Cortex;Cats}, Medline = {93011768}, Nlm_Id = {0043312}, Number = {2}, Organization = {Institut d'Anatomie, Lausanne, Switzerland.}, Pages = {346-58}, Pubmed = {1383021}, Title = {Emergence of callosally projecting neurons with stellate morphology in the visual cortex of the kitten}, Uuid = {B9F44620-EE16-11DA-8605-000D9346EC2A}, Volume = {90}, Year = {1992}} @article{Vercelli:1993, Abstract = {In kittens, callosally projecting neurons were labeled by retrograde transport of FITC- (fluorescein isothiocyanate)- and TRITC- (tetramethylrhodamine isothiocyanate)-conjugated latex microspheres injected in two different visual areas (17, 17/18, 19, or postero-medial lateral suprasylvian; PMLS) at postnatal day 3. At postnatal day 57 more than 1200 labeled neurons in visual cortical areas were intracellularly injected with 3\%lucifer yellow (LY) in perfusion-fixed slices of the contralateral hemisphere. The distribution of labeled neurons was charted, and LY-filled neurons were classified on the basis of their area and layer of location, and dendritic pattern. The dendritic arbors of 120 neurons were computer reconstructed. For the basal dendrites of supragranular pyramidal neurons a statistical analysis of number of nodes, internodal and terminal segment lengths, and total dendritic length was run relative to the area of location and axonal projection. Connections were stronger between homotopic than between heterotopic areas. Overall tangential and laminar distributions depended on the area injected. Qualitative morphological differences were found among callosally projecting neurons, related to the area of location, not to that of projection. In all projections from areas 17 and 18, pyramidal and spinous stellate neurons were found in supragranular layers. In contrast, spinous stellate neurons lacked in projections from area 19, 21a, PMLS and postero-lateral lateral suprasylvian (PLLS). In all areas, the infragranular neurons showed heterogeneous typology, but in PMLS no fusiform cells were found. Quantitative analysis of basal dendrites did not reveal significant differences in total dendritic length, terminal, or intermediate segment length among neurons in area 17 or 18, and this was related to whether they projected to contralateral areas 17-18 or PMLS. All injections produced exuberant labeling in area 17. No differences could be found between neurons in area 17 (with transient axons through the corpus callosum) and neurons near the 17/18 border (which maintain projections to the corpus callosum). In conclusion, morphology of callosally projecting neurons seems to relate more to intrinsic specificities in the cellular composition of each area than to the area of contralateral axonal projection or the fate of callosal axons.}, Author = {Vercelli, A. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Fluorescent Dyes;Rhodamines;Animals;Visual Pathways;Fluorescein-5-isothiocyanate;Not relevant;11 Glia;Pyramidal Tracts;Dendrites;Support, Non-U.S. Gov't;Cerebral Cortex;Neurons;Isoquinolines;Horseradish Peroxidase;Laterality;Computer Graphics;Corpus Callosum;Cats}, Medline = {93365611}, Nlm_Id = {0043312}, Number = {3}, Organization = {Institut d'Anatomie, Lausanne, Switzerland.}, Pages = {393-404}, Pubmed = {8359254}, Title = {Morphology of visual callosal neurons with different locations, contralateral targets or patterns of development}, Uuid = {27EB4803-5187-4F6A-837C-51A4203F048C}, Volume = {94}, Year = {1993}} @article{Vergano-Vera:2006, Abstract = {During the embryonic period, many olfactory bulb (OB) interneurons arise in the lateral ganglionic eminence (LGE) from precursor cells expressing Dlx2, Gsh2 and Er81 transcription factors. Whether GABAergic and dopaminergic interneurons are also generated within the embryonic OB has not been studied thoroughly. In contrast to abundant Dlx2 and Gsh2 expression in ganglionic eminences (GE), Dlx2 and Gsh2 proteins are not expressed in the E12.5-13.5 mouse OB, whereas the telencephalic pallial domain marker Pax6 is abundant. We found GABAergic and dopaminergic neurons originating from dividing precursor cells in E13.5 OB and in short-term dissociated cultures prepared from the rostral half of E13.5 OB. In OB cultures, 22\%of neurons were GAD+, of which 53\%were Dlx2+, whereas none expressed Gsh2. By contrast, 70\%of GAD+ cells in GE cultures were Dlx2+ and 16\%expressed Gsh2. In E13.5 OB slices transplanted with EGFP-labeled E13.5 OB precursor cells, 31.7\%of EGFP+ cells differentiated to GABAergic neurons. OB and LGE precursors transplanted into early postnatal OB migrated and differentiated in distinct patterns. Transplanted OB precursors gave rise to interneurons with dendritic spines in close proximity to synaptophysin-positive boutons. Interneurons were also abundant in differentiating OB neural stem cell cultures; the neurons responded to the neurotrophin Bdnf and expressed presynaptic proteins. In vivo, the Bdnf receptor TrkB colocalized with synaptic proteins at the glomeruli. These findings suggest that, in addition to receiving interneurons from the LGE, the embryonic OB contains molecularly distinct local precursor cells that generate mature GABAergic and dopaminergic neurons.}, Author = {Verga\~{n}o-Vera, Eva and Yusta-Boyo, Mar{\'\i}a J. and de Castro, Fernando and Bernad, Antonio and de Pablo, Flora and Vicario-Abej{\'o}n, Carlos}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8701744}, Number = {21}, Organization = {Instituto Cajal, Consejo Superior de Investigaciones Cient{\'\i}ficas (CSIC), Spain.}, Pages = {4367-79}, Pii = {133/21/4367}, Pubmed = {17038521}, Title = {Generation of GABAergic and dopaminergic interneurons from endogenous embryonic olfactory bulb precursor cells}, Uuid = {50B0BC5F-C574-49F4-89F7-D15F22132D3B}, Volume = {133}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.02601}} @article{Verney:2000, Abstract = {We estimated the proportion of cells eliminated by histogenetic cell death during the first 2 postnatal weeks in areas 1, 3 and 40 of the mouse parietal neocortex. For each layer and for the subcortical white matter in each neocortical area, the number of dying cells per mm(2) was calculated and the proportionate cell death for each day of the 2-week interval was estimated. The data show that cell death proceeds essentially uniformly across the neocortical areas and layers and that it does not follow either the spatiotemporal gradient of cell cycle progression in the pseudostratified ventricular epithelium of the cerebral wall, the source of neocortical neurons, or the 'inside-out' neocortical neuronogenetic sequence. Therefore, we infer that the control mechanisms of neocortical histogenetic cell death are independent of mechanisms controlling neuronogenesis or neuronal migration but may be associated with the ingrowth, expansion and a system-wide matching of neuronal connectivity.}, Author = {Verney, C. and Takahashi, T. and Bhide, P. G. and Nowakowski, R. S. and Caviness, V. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {Mice, Inbred Strains;Research Support, Non-U.S. Gov't;Apoptosis;Research Support, U.S. Gov't, P.H.S.;Neocortex;Cell Division;Cell Cycle;Animals, Newborn;Cell Death;Research Support, U.S. Gov't, Non-P.H.S.;Mice;Animals;24 Pubmed search results 2008;Neurons;In Situ Nick-End Labeling}, Medline = {20125907}, Nlm_Id = {7809375}, Number = {1-2}, Organization = {Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass., USA.}, Pages = {125-38}, Pii = {dne22125}, Pubmed = {10657705}, Title = {Independent controls for neocortical neuron production and histogenetic cell death}, Uuid = {C6CD6215-F2C6-48B5-BD28-C6C796216D0B}, Volume = {22}, Year = {2000}} @article{Verstegen:1998, Abstract = {In vivo expansion and multilineage outgrowth of human immature hematopoietic cell subsets from umbilical cord blood (UCB) were studied by transplantation into hereditary immunodeficient (SCID) mice. The mice were preconditioned with Cl2MDP-liposomes to deplete macrophages and 3.5 Gy total body irradiation (TBI). As measured by immunophenotyping, this procedure resulted in high levels of human CD45(+) cells in SCID mouse bone marrow (BM) 5 weeks after transplantation, similar to the levels of human cells observed in NOD/SCID mice preconditioned with TBI. Grafts containing approximately 10(7) unfractionated cells, approximately 10(5) purified CD34+ cells, or 5 x 10(3) purified CD34+CD38- cells yielded equivalent numbers of human CD45+ cells in the SCID mouse BM, which contained human CD34+ cells, monocytes, granulocytes, erythroid cells, and B lymphocytes at different stages of maturation. Low numbers of human GpA+ erythroid cells and CD41+ platelets were observed in the peripheral blood of engrafted mice. CD34+CD38+ cells (5 x 10(4)/mouse) failed to engraft, whereas CD34- cells (10(7)/mouse) displayed only low levels of chimerism, mainly due to mature T lymphocytes. Transplantation of graded numbers of UCB cells resulted in a proportional increase of the percentages of CD45+ and CD34+ cells produced in SCID mouse BM. In contrast, the number of immature, CD34+CD38- cells produced in vivo showed a second-order relation to CD34+ graft size, and mice engrafted with purified CD34+CD38- grafts produced 10-fold fewer CD34+ cells without detectable CD34+CD38- cells than mice transplanted with equivalent numbers of unfractionated or purified CD34+ cells. These results indicate that SCID repopulating CD34+CD38- cells require CD34+CD38+ accessory cell support for survival and expansion of immature cells, but not for production of mature multilineage progeny in SCID mouse BM. These accessory cells are present in the purified, nonrepopulating CD34+CD38+ subset as was directly proven by the ability of this fraction to restore the maintenance and expansion of immature CD34+CD38- cells in vivo when cotransplanted with purified CD34+CD38- grafts. The possibility to distinguish between maintenance and outgrowth of immature repopulating cells in SCID mice will facilitate further studies on the regulatory functions of accessory cells, growth factors, and other stimuli. Such information will be essential to design efficient stem cell expansion procedures for clinical use.}, Author = {Verstegen, M. M. and van Hennik, P. B. and Terpstra, W. and van den Bos, C. and Wielenga, J. J. and van Rooijen, N. and Ploemacher, R. E. and Wagemaker, G. and Wognum, A. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Mice, Inbred NOD;ADP-ribosyl Cyclase;Humans;Macrophages;Animals;Transplantation, Heterologous;Comparative Study;Antigens, Differentiation;Female;Antigens, CD;NAD+ Nucleosidase;Mice, SCID;Antigens, CD34;11 Glia;Specific Pathogen-Free Organisms;Radiation Chimera;Hematopoietic Stem Cell Transplantation;Hematopoiesis;Cell Lineage;Mice;Transplantation Conditioning;Fetal Blood;Graft Survival;Hematopoietic Stem Cells;Clodronic Acid;Research Support, Non-U.S. Gov't}, Medline = {98158631}, Month = {3}, Nlm_Id = {7603509}, Number = {6}, Organization = {Institute of Hematology, Erasmus University Rotterdam, Rotterdam, The Netherlands.}, Pages = {1966-76}, Pubmed = {9490679}, Title = {Transplantation of human umbilical cord blood cells in macrophage-depleted SCID mice: evidence for accessory cell involvement in expansion of immature CD34+CD38- cells}, Uuid = {2BD00B5D-2C6C-4A50-AD1C-7EB559BDAD14}, Volume = {91}, Year = {1998}} @article{Veruki:2002, Abstract = {AII (rod) amacrine cells in the mammalian retina are reciprocally connected via gap junctions, but there is no physiological evidence that demonstrates a proposed function as electrical synapses. In whole-cell recordings from pairs of AII amacrine cells in a slice preparation of the rat retina, bidirectional, nonrectifying electrical coupling was observed in all pairs with overlapping dendritic trees (average conductance approximately 700 pS). Coupling displayed characteristics of a low-pass filter, with no evidence for amplification of spike-evoked electrical postsynaptic potentials by active conductances. Coincidence detection, as well as precise temporal synchronization of subthreshold membrane potential oscillations and TTX-sensitive spiking, was commonly observed. These results indicate a unique mode of operation and integrative capability of the network of AII amacrine cells. 0896-6273 Journal Article}, Author = {Veruki, M. L. and Hartveit, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:12:00 -0400}, Journal = {Neuron}, Keywords = {Patch-Clamp Techniques;Action Potentials/physiology;Rats;Retina/cytology/*physiology;Nerve Net/cytology/*physiology;H pdf;Time Factors;In Vitro;12 Interneuron development;Support, Non-U.S. Gov't;Animals;Synaptic Transmission/physiology;Gap Junctions/*metabolism;Amacrine Cells/cytology/*metabolism}, Number = {6}, Organization = {University of Bergen, Department of Anatomy and Cell Biology, Arstadveien 19, N-5009 Bergen, Norway.}, Pages = {935-46}, Title = {AII (Rod) amacrine cells form a network of electrically coupled interneurons in the mammalian retina}, Uuid = {8AB66AED-D3F7-426B-833F-265E04070D32}, Volume = {33}, Year = {2002}, url = {papers/Veruki_Neuron2002.pdf}} @article{Vicario-Abejon:1995, Abstract = {Restrictions in neuronal fate occur during the transition from a multipotential to a postmitotic cell. This and later steps in neuronal differentiation are determined by extracellular signals. We report that basic fibroblast growth factor is mitogenic for stem cells and is a differentiation factor for calbindin-expressing hippocampal neurons. The neurotrophin NT-3 is a differentiation factor for the same neurons but does not affect proliferation. NT-3 and brain-derived neurotrophic factor promote the maturation of neurons derived from stem cells that have been grown in vitro. These results define functions for basic fibroblast growth factor and neurotrophins in the differentiation processes that direct a multipotential stem cell to a specific neuronal fate.}, Author = {Vicario-Abejon, C. and Johe, K. K. and Hazel, T. G. and Collazo, D. and McKay, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {Cell Differentiation/drug effects;Nerve Growth Factors/*pharmacology;Hippocampus/*cytology/drug effects;Rats;C-4;Neurons/cytology/*drug effects;Stem Cells/cytology/drug effects;Brain-Derived Neurotrophic Factor;Neurotrophin 3;Animal;Cell Count;Rats, Sprague-Dawley;Calcium-Binding Protein, Vitamin D-Dependent/drug effects;Fibroblast Growth Factor, Basic/*pharmacology;Nerve Tissue Proteins/drug effects/*pharmacology;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Cells, Cultured/cytology/drug effects;Biological Markers}, Number = {1}, Organization = {Laboratory of Molecular Biology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.}, Pages = {105-14.}, Title = {Functions of basic fibroblast growth factor and neurotrophins in the differentiation of hippocampal neurons}, Uuid = {FF169870-A6ED-489A-B864-CAFF6EA9CA9B}, Volume = {15}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=7619514}} @article{Vicario-Abejon:1995a, Abstract = {During the development of the CNS, a salient issue is whether neuronal phenotype is defined by the lineage or by the environment of precursor cells. Transplants permit these two possibilities to be tested, as cell fate can be examined in a new location. Dissociated cerebellar cells from newborn rats treated with tritiated thymidine or from NSE-lacZ transgenic mice were grafted into the dentate gyrus of the developing hippocampus. Implanted cells integrated into the granule cell layer, which contains the cell bodies of host granule neurons. Immunohistochemistry showed that grafted cells in the granule cell layer, like the host hippocampal granule neurons, were calbindin positive and upregulated FOS in a seizure paradigm. Electron microscopic analysis also showed that cells grafted to the dentate gyrus share features with host dentate neurons. These assays indicate that transplanted cerebellar cells acquired morphological and antigenic features characteristic of hippocampal neurons. These results show that metencephalic precursors are capable of differentiating in response to signals in the telencephalon, suggesting that the environment controls the regional fate of neuronal precursor cells during neurogenesis.}, Author = {Vicario-Abej{\'o}n, C. and Cunningham, M. G. and McKay, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0270-6474}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;10 Development;Research Support, Non-U.S. Gov't;Rats, Sprague-Dawley;Cell Transplantation;Rats;10 Hippocampus;Hippocampus;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Dentate Gyrus;Cerebellum;Mice, Transgenic;Animals, Newborn;Mice;Animals;Neurons}, Medline = {96033731}, Month = {10}, Nlm_Id = {8102140}, Number = {10}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA.}, Pages = {6351-63}, Pubmed = {7472400}, Title = {Cerebellar precursors transplanted to the neonatal dentate gyrus express features characteristic of hippocampal neurons}, Uuid = {DB225F9F-D7BC-432D-99B8-CAF1F783FA29}, Volume = {15}, Year = {1995}} @article{Victor:2005, Abstract = {Quantifying similarity and dissimilarity of spike trains is an important requisite for understanding neural codes. Spike metrics constitute a class of approaches to this problem. In contrast to most signal-processing methods, spike metrics operate on time series of all-or-none events, and are, thus, particularly appropriate for extracellularly recorded neural signals. The spike metric approach can be extended to multineuronal recordings, mitigating the 'curse of dimensionality' typically associated with analyses of multivariate data. Spike metrics have been usefully applied to the analysis of neural coding in a variety of systems, including vision, audition, olfaction, taste and electric sense.}, Author = {Victor, Jonathan D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {21 Neurophysiology;Action Potentials;Algorithms;Models, Neurological;research support, n.i.h., extramural;research support, u.s. gov't, p.h.s.;Animals;Humans;24 Pubmed search results 2008;review;Neurons}, Month = {10}, Nlm_Id = {9111376}, Number = {5}, Organization = {Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA. jdvicto\@med.cornell.edu}, Pages = {585-92}, Pii = {S0959-4388(05)00123-6}, Pubmed = {16140522}, Title = {Spike train metrics}, Uuid = {514CECB1-3466-47FC-8A9C-841C14F9837C}, Volume = {15}, Year = {2005}, url = {papers/Victor_CurrOpinNeurobiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2005.08.002}} @article{Vignery:2000, Abstract = {Membrane fusion is a ubiquitous event that occurs in a wide range of biological processes. While intracellular membrane fusion mediating organelle trafficking is well understood, much less is known about cell-cell fusion mediating sperm cell-oocyte, myoblast-myoblast and macrophage-macrophage fusion. In the case of mononuclear phagocytes, their fusion is not only associated with the differentiation of osteoclasts, cells which play a key role in the pathogenesis of osteoporosis, but also of giant cells that are present in chronic inflammatory reactions and in tumours. Despite the biological and pathophysiological importance of intercellular fusion events, the actual molecular mechanism of macrophage fusion is still unclear. One of the main research themes in my laboratory has been to investigate the molecular mechanism of mononuclear phagocyte fusion. Our hypothesis has been that macrophage-macrophage fusion, similar to virus-cell fusion, is mediated by specific cell surface proteins. But, in contrast with myoblasts and sperm cells, macrophage fusion is a rare event that occurs in specific instances. To test our hypothesis, we established an in vitro cell-cell fusion assay as a model system which uses alveolar macrophages. Upon multinucleation, these macrophages acquire the osteoclast phenotype. This indicates that multinucleation of macrophages leads to a specific and novel functional phenotype in macrophages. To identify the components of the fusion machinery, we generated four monoclonal antibodies (mAbs) which block the fusion of alveolar macrophages and purified the unique antigen recognized by these mAbs. This led us to the cloning of MFR (Macrophage Fusion Receptor). MFR was cloned simultaneously as P84/SHPS-1/SIRPalpha/BIT by other laboratories. We subsequently showed that the recombinant extracellular domain of MFR blocks fusion. Most recently, we identified a lower molecular weight form of MFR that is missing two extracellular immunoglobulin (Ig) C domains. Shortly after we cloned MFR, CD47 was reported to be a ligand for P84/SIRPalpha. We have since generated preliminary results which suggest that CD47 interacts with MFR during adhesion/fusion and is a member of the fusion machinery. We also identified CD44 as a plasma membrane protein which, like MFR, is highly expressed at the onset of fusion. The recombinant soluble extracellular domain of CD44 blocks fusion by interacting with a cell-surface binding site. We now propose a model in which both forms of MFR, CD44, and CD47 mediate macrophage adhesion/fusion and therefore the differentiation of osteoclasts and giant cells.}, Author = {Vignery, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0959-9673}, Journal = {Int J Exp Pathol}, Keywords = {Humans;Carrier Proteins;Macrophages;review;Antigens, CD47;Antigens, Differentiation;Antigens, CD;Cell Fusion;Antigens, CD44;Receptors, Immunologic;Giant Cells;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;Membrane Glycoproteins;Viral Physiology;Neural Cell Adhesion Molecule L1;24 Pubmed search results 2008;Osteoclasts;Neural Cell Adhesion Molecules}, Medline = {21094981}, Month = {10}, Nlm_Id = {9014042}, Number = {5}, Organization = {Yale University School of Medicine, Department of Orthopaedics and Rehabilitation, New Haven, CT 06510, USA. agnes.vignery\@yale.edu}, Pages = {291-304}, Pii = {iep164}, Pubmed = {11168677}, Title = {Osteoclasts and giant cells: macrophage-macrophage fusion mechanism}, Uuid = {2AEABBC4-E9E0-11DA-920C-000D9346EC2A}, Volume = {81}, Year = {2000}, url = {papers/Vignery_IntJExpPathol2000.pdf}} @article{Vignery:2005, Abstract = {The fusion of cells is a fundamental biological event that is essential for a variety of developmental and homeostatic processes. Fusion is required for the formation of multinucleated osteoclasts and giant cells, although the mechanisms that govern these processes are poorly understood. A new study now reveals an unexpected role for the receptor, dendritic cell-specific transmembrane protein (DC-STAMP), in this process. The potential mechanism by which DC-STAMP governs fusion and the implications of this finding will be discussed.}, Author = {Vignery, Agn\`{e}s}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0022-1007}, Journal = {J Exp Med}, Keywords = {11 Glia}, Month = {8}, Nlm_Id = {2985109R}, Number = {3}, Organization = {Yale University School of Medicine, New Haven, CT 06510.}, Pages = {337-40}, Pii = {jem.20051123}, Pubmed = {16061722}, Title = {Macrophage fusion: the making of osteoclasts and giant cells}, Uuid = {81CCBB7C-99E0-4320-94C7-F85DD9630C4B}, Volume = {202}, Year = {2005}, url = {papers/Vignery_JExpMed2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1084/jem.20051123}} @article{Vignery:2005a, Abstract = {Macrophages are present in all tissues and can fuse with themselves to differentiate into multinucleate osteoclasts or giant cells that play a central role in osteoporosis and chronic inflammatory diseases, respectively. Yet, the mechanism by which they fuse remains uncharacterized. The macrophage fusion receptor (MFR) and its ligand CD47 might mediate homotypic fusion of macrophages and allow for their recognition as 'self' before fusion. Although a novel process and controversial idea, macrophages might exploit a similar mechanism for fusion with somatic cells or tumor cells, with resultant organ repair or metastasis, respectively. Hence, macrophages might be the 'double-edged swords' of tissues.}, Author = {Vignery, Agn\`{e}s}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0962-8924}, Journal = {Trends Cell Biol}, Keywords = {Membrane Glycoproteins;Cell Fusion;Alpha;Cell Proliferation;Antigens, Differentiation;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;Antigens, CD;Tumor Stem Cells;Research Support, N.I.H., Extramural;11 Glia;review, tutorial;Macrophages;Humans;Receptors, Immunologic;review}, Month = {4}, Nlm_Id = {9200566}, Number = {4}, Organization = {Yale University School of Medicine, Dept of Orthopaedics and Rehabilitation, TMP534, 310 Cedar Street, New Haven CT 06510, USA. agnes.vignery\@yale.edu}, Pages = {188-93}, Pii = {S0962-8924(05)00052-8}, Pubmed = {15817374}, Title = {Macrophage fusion: are somatic and cancer cells possible partners?}, Uuid = {6CE27E5F-E9C0-11DA-920C-000D9346EC2A}, Volume = {15}, Year = {2005}, url = {papers/Vignery_TrendsCellBiol2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.tcb.2005.02.008}} @article{Vincent:2006, Abstract = {Despite traditional theories emphasizing parietal contributions to spatial attention and sensory-motor integration, functional MRI (fMRI) experiments in normal subjects suggest that specific regions within parietal cortex may also participate in episodic memory. Here we examined correlations in spontaneous blood-oxygenation-level-dependent (BOLD) signal fluctuations in a resting state to identify the network associated with the hippocampal formation (HF) and determine whether parietal regions were elements of that network. In the absence of task, stimuli, or explicit mnemonic demands, robust correlations were observed between activity in the HF and several parietal regions (including precuneus, posterior cingulate, retrosplenial cortex, and bilateral inferior parietal lobule). These HF-correlated regions in parietal cortex were spatially distinct from those correlated with the motion-sensitive MT+ complex. Reanalysis of event-related fMRI studies of recognition memory showed that the regions spontaneously correlated with the HF (but not MT+) were also modulated during directed recollection. These regions showed greater activity to successfully recollected items as compared with other trial types. Together, these results associate specific regions of parietal cortex that are sensitive to successful recollection with the HF.}, Author = {Vincent, Justin L. and Snyder, Abraham Z. and Fox, Michael D. and Shannon, Benjamin J. and Andrews, Jessica R. and Raichle, Marcus E. and Buckner, Randy L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Adolescent;Magnetic Resonance Imaging;Electrophysiology;Humans;Memory;Algorithms;Oxygen;Functional Laterality;Parietal Lobe;Female;Hippocampus;research support, non-u.s. gov't;Male;Nerve Net;21 Neurophysiology;Adult;Cognition;research support, n.i.h., extramural;Mental Recall;24 Pubmed search results 2008;research support, u.s. gov't, non-p.h.s.;Data Interpretation, Statistical;Brain Mapping}, Month = {12}, Nlm_Id = {0375404}, Number = {6}, Organization = {Mallinckrodt Institute of Radiology, and Department of Neurology, Washington University School of Medicine, 4525 Scott Avenue, St. Louis, MO 63110, USA.}, Pages = {3517-31}, Pii = {00048.2006}, Pubmed = {16899645}, Title = {Coherent spontaneous activity identifies a hippocampal-parietal memory network}, Uuid = {BD7F0B0F-0C3A-4257-A5FD-9DD72D369587}, Volume = {96}, Year = {2006}, url = {papers/Vincent_JNeurophysiol2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00048.2006}} @article{Vincent:2007, Abstract = {The traditional approach to studying brain function is to measure physiological responses to controlled sensory, motor and cognitive paradigms. However, most of the brain's energy consumption is devoted to ongoing metabolic activity not clearly associated with any particular stimulus or behaviour. Functional magnetic resonance imaging studies in humans aimed at understanding this ongoing activity have shown that spontaneous fluctuations of the blood-oxygen-level-dependent signal occur continuously in the resting state. In humans, these fluctuations are temporally coherent within widely distributed cortical systems that recapitulate the functional architecture of responses evoked by experimentally administered tasks. Here, we show that the same phenomenon is present in anaesthetized monkeys even at anaesthetic levels known to induce profound loss of consciousness. We specifically demonstrate coherent spontaneous fluctuations within three well known systems (oculomotor, somatomotor and visual) and the 'default' system, a set of brain regions thought by some to support uniquely human capabilities. Our results indicate that coherent system fluctuations probably reflect an evolutionarily conserved aspect of brain functional organization that transcends levels of consciousness.}, Author = {Vincent, J. L. and Patel, G. H. and Fox, M. D. and Snyder, A. Z. and Baker, J. T. and Van Essen, D. C. and Zempel, J. M. and Snyder, L. H. and Corbetta, M. and Raichle, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {research support, non-u.s. gov't;21 Neurophysiology;research support, u.s. gov't, non-p.h.s.;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0410462}, Number = {7140}, Organization = {Department of Radiology, Washington University in St Louis, Missouri 63110, USA.}, Pages = {83-6}, Pii = {nature05758}, Pubmed = {17476267}, Title = {Intrinsic functional architecture in the anaesthetized monkey brain}, Uuid = {2981CB9C-A906-4DEA-89E4-1D5D9881B6A8}, Volume = {447}, Year = {2007}, url = {papers/Vincent_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05758}} @article{Vincent:2002, Abstract = {Macrophage colony stimulating factor (M-CSF) is a microglial activator expressed at increased levels in the brain in Alzheimer's disease. In monotypic microglial cultures, M-CSF strongly augments amyloid beta (Abeta) induced microglial production of proinflammatory cytokines and nitric oxide. However, this augmentation could be due to strong autocrine and paracrine effects in monotypic cultures. We used hippocampal organotypic cultures to test M-CSF/Abeta augmentation in a system modeling intact brain. Combined M-CSF/Abeta treatment increased interleukin-1 (IL-1) and macrophage inflammatory protein 1-alpha expression by microglia, whereas inducible nitric oxide synthase (iNOS) expression was localized primarily to astroglia. Induction of cytokines and iNOS was also observed after lipopolysaccharide treatment of organotypic hippocampal cultures, but iNOS expression was localized mainly to microglia rather than astrocytes. Treatment with M-CSF/Abeta did not result in neuronal death. These results demonstrate that combined M-CSF/Abeta treatment results in a strong inflammatory response in the organotypic environment without inducing neurotoxicity.}, Author = {Vincent, Valerie A. M. and Selwood, Simon P. and Murphy, Greer M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0197-4580}, Journal = {Neurobiol Aging}, Keywords = {Animals;Astrocytes;Amyloid beta-Protein;Rats;Comparative Study;Adjuvants, Immunologic;Microglia;Enzyme Induction;Lipopolysaccharides;Rats, Sprague-Dawley;Hippocampus;Drug Combinations;11 Glia;Nitric-Oxide Synthase;RNA, Messenger;Support, Non-U.S. Gov't;Peptide Fragments;Neurons;Interleukin-1;Support, U.S. Gov't, P.H.S.;Macrophage Colony-Stimulating Factor;Macrophage Inflammatory Protein-1;Interleukin-6;Inflammation;Cell Death;Organ Culture;Nitric Oxide}, Medline = {21956959}, Nlm_Id = {8100437}, Number = {3}, Organization = {Department of Psychiatry and Behavioral Sciences, Neuroscience Research Laboratories, Stanford University School of Medicine, Stanford, CA 94305-5485, USA.}, Pages = {349-62}, Pii = {S0197458001003384}, Pubmed = {11959396}, Title = {Proinflammatory effects of M-CSF and A beta in hippocampal organotypic cultures}, Uuid = {B957C0EA-922C-4CB1-84CF-44BB6C194D31}, Volume = {23}, Year = {2002}} @article{Virag:2003, Abstract = {Granulation tissue formation is a critical step in infarct repair, however, the kinetics of cell replication and the molecules that regulate this process are poorly understood. In uninjured mouse hearts and at 2 days post-infarction, very little DNA synthesis (measured by incorporation of a BrdU pulse) was detected in any cell type. Four days after permanent coronary occlusion, the rates of myofibroblast (smooth muscle alpha-actin and BrdU double-positive) and endothelial cell (CD31 and BrdU double-positive) proliferation were 15.4 +/- 1.1\%and 2.9 +/- 0.5\%, respectively. Most proliferating cells were located at the interface of the infarct and viable tissue. By 1 week, fibroblast and endothelial cell proliferation declined to 4.1 +/- 0.6\%and 0.7 +/- 0.1\%, respectively. In the 2-week infarct, the remaining necrosis had been phagocytosed, and fibroblast and endothelial cell proliferation were <0.5\%. Although leukocytes were abundant throughout infarct repair, no significant proliferation was detected at any time in cells expressing CD45 or mac-3. Infarct size at 4 days was 38 +/- 5\%of the left ventricle and contracted to 20 +/- 4\%by 4 weeks. After 4 days, the chamber dilated to four times that of the control hearts and remained so for the duration of the time course. The vascular density (per mm(2)) declined from 3643 +/- 82 in control hearts to 2716 +/- 197 at 1 week and 1010 +/- 47 at 4 weeks post-myocardial infarction (MI). The average percent area occupied by vessels did not change significantly between the groups but the area/vessel ( micro m(2)) increased from 14.1 +/- 0.3 in control hearts to 16.9 +/- 1.9 at 1 week and 38.7 +/- 7.9 at 4 weeks post-MI. These data indicate that mitogens for fibroblasts and endothelial cells peak within 4 days of infarction in the mouse heart. This provides the basis for identifying the responsible molecules and developing strategies to alter wound repair and improve cardiac function. 0002-9440 Journal Article}, Author = {Virag, J. I. and Murry, C. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Am J Pathol}, Keywords = {EE;Muscle, Smooth/*pathology;Endothelial Cells/pathology;08 Aberrant cell cycle;Time Factors;Cell Division;Mice, Inbred C57BL;Myocardium/*pathology;Chronic Disease;*Wound Healing;Support, U.S. Gov't, P.H.S.;Animals;Mice;Leukocytes/pathology;Fibroblasts/*pathology;Myocardial Infarction/*pathology/*physiopathology}, Number = {6}, Organization = {Department of Pathology, University of Washington, Seattle, Washington 98195, USA.}, Pages = {2433-40}, Pubmed = {14633615}, Title = {Myofibroblast and endothelial cell proliferation during murine myocardial infarct repair}, Uuid = {8DC42CD4-49A0-4A95-BD3E-DA8B7109291F}, Volume = {163}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14633615}} @article{Vitry:2003, Abstract = {Finding ways to enhance remyelination is a major challenge in treating demyelinating diseases. Recent studies have suggested that circulating bone marrow cells can home in brain and transdifferentiate into neural cells. To ask whether hematopoietic precursors can form myelinating cells, we investigated the neuropoietic potential of embryonic precursors sorted from the mouse aorta-gonads-mesonephros (AGM) region. This cell fraction is capable of long-term hematopoietic reconstitution and generates colonies containing multipotential precursors and lymphoid or erythro-myeloid progenies. When cultured in hematopoietic growth conditions, a fraction of CD45-positive AGM cells coexpress neural markers such as nestin, the polysialylated form of neural cell adhesion molecule, the betaIII tubulin isoform, and glial fibrillary acidic protein. However, when hematopoietic precursors containing green fluorescent protein were cocultured with embryonic striatal precursors into neurospheres, they maintained their hematopoietic phenotype without undergoing differentiation into neurons, astrocytes, or oligodendrocytes. After intraventricular grafting, hematopoietic precursors integrated into the brain of wild-type or hypomyelinated newborn shiverer mice and gave rise to microglia but not neurons or glia. In contrast, when wild-type embryonic striatal neurospheres were grafted in shiverer, they formed numerous myelin internode patches. Even when neural and hematopoietic precursors were grafted together into shiverer mice, only neural precursors generated myelin-forming cells and synthesized myelin. Thus, embryonic neurospheres have myelin repair properties not shown by embryonic hematopoietic precursors. This suggests that the use of multipotential neural precursors to generate myelin-forming cells remains one of the most promising avenues toward remyelination therapies.}, Author = {Vitry, Sandrine and Bertrand, Julien Y. and Cumano, Ana and Dubois-Dalcq, Monique}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Cell Culture Techniques;Myelin Sheath;Cells, Cultured;Gonads;Mesonephros;Animals;Cell Separation;Antigens, Differentiation;Mice, Inbred C3H;Female;Microglia;Mice, Transgenic;Mice, Inbred C57BL;Mice, Neurologic Mutants;Oligodendroglia;Crosses, Genetic;Male;Aorta;Hematopoietic Stem Cell Transplantation;Animals, Newborn;Neurons;Flow Cytometry;Hematopoietic Stem Cells;Mice;24 Pubmed search results 2008;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {22989858}, Month = {11}, Nlm_Id = {8102140}, Number = {33}, Organization = {Unit{\'e} de Neurovirologie et R{\'e}g{\'e}n{\'e}ration du Syst\`{e}me Nerveux Centre National de la Recherche Scientifique 1961, Institut Pasteur, 75724, Paris, Cedex 15, France.}, Pages = {10724-31}, Pii = {23/33/10724}, Pubmed = {14627658}, Title = {Primordial hematopoietic stem cells generate microglia but not myelin-forming cells in a neural environment}, Uuid = {153FF7C6-93F4-474C-B0F4-B06FEDF89C5E}, Volume = {23}, Year = {2003}} @article{Vives:2003, Abstract = {S100B, the EF-hand Ca(++)-binding protein with gliotrophic and neurotrophic properties implicated in the pathogenesis of Alzheimer's disease, is coined as a glial marker, despite its documented presence in rodent brain neurons. We have generated a transgenic mouse whose EGFP reporter, controlled by the -1,669/+3,106 sequence of the murine S100B gene, allows the direct microscopic observation of most S100B-expressing cells in the central nervous system (CNS). From embryonic day 13 onward, EGFP expression was targeted to selected neuroepithelial, glial, and neuronal cells, indicating that cell-specific expression of S100B is regulated at the transcriptional level during development. In adult mice, the highest level of EGFP expression was found in ependymocytes; astrocytes; and spinal, medullar, pontine, and deep cerebellar S100B neurons. Our results, thus, agree with earlier reports suggesting that S100B is not a CNS glial-specific marker. In addition, we detected EGFP and S100B in forebrain neurons previously thought not to express S100B in the mouse, including neurons of primary motor and somatosensory neocortical areas, the ventral pallidum and prerubral field. Another interesting finding was the selected EGFP targeting to neonatal S100B oligodendrocytes and adult NG2 progenitors as opposed to mature S100B oligodendrocytes. This finding suggests that, except for oligodendrocytes at the last stage of myelin maturation, the -1,669/+3,106 sequence of the S100B gene is a useful reagent for driving expression of transgenes in most S100B-expressing cells of mouse brain. 0021-9967 Journal Article}, Author = {Vives, V. and Alonso, G. and Solal, A. C. and Joubert, D. and Legraverend, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Comp Neurol}, Keywords = {02 Adult neurogenesis migration;Nerve Growth Factors/*metabolism;Neurons/*metabolism;BB pdf;03 Adult neurogenesis progenitor source;Central Nervous System/*metabolism;Neuroglia/*metabolism;Mice, Transgenic;Luminescent Proteins/genetics/*metabolism;S100 Proteins/*metabolism;Fluorescent Antibody Technique;Blotting, Western;Animals;Support, Non-U.S. Gov't;Mice}, Number = {4}, Organization = {Institut National de la Sante et de la Recherche Medicale U469, Centre CNRS-INSERM de Pharmacologie et d'Endocrinologie, F-34094 Montpellier Cedex 05, France.}, Pages = {404-19}, Pubmed = {12561079}, Title = {Visualization of S100B-positive neurons and glia in the central nervous system of EGFP transgenic mice}, Uuid = {97243622-E035-4D16-B39B-71D05CF0EB1F}, Volume = {457}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12561079}} @article{Voelker:2004, Abstract = {There are two main types of layer V pyramidal neurons in rat cortex. Type I neurons have tufted apical dendrites extending into layer I, produce bursts of action potentials and project to subcortical targets (spinal cord, superior colliculus and pontine nuclei). Type II neurons have apical dendrites, which arborize in layers II-IV, do not produce bursts of action potentials and project to ipsilateral and contralateral cortex. The specific expression of different genes and proteins in these two distinct layer V neurons is unknown. To distinguish between distinct subpopulations, fluorescent microspheres were injected into subcortical targets (labeling type I neurons) or primary somatosensory cortex (labeling type II neurons) of adult rats. After transport, cortical sections were processed for immunohistochemistry using various antibodies. This study demonstrated that antigens recognized by SMI-32, N200 and FNP-7 antibodies were only expressed in subcortical (type I)--but not in contralateral (type II)--projecting neurons. NR1, NR2a/b, PLCbeta1, BDNF, NGF and TrkB antigens were highly expressed in all neuronal subpopulations examined. Organotypic culture experiments demonstrated that the development of neurofilament expression and laminar specificity does not depend on the presence of the subcortical targets. This study suggests specific markers for the subcortical projecting layer V neuron subpopulations.}, Author = {Voelker, Courtney C. J. and Garin, Nathalie and Taylor, Jeremy S. H. and G{\"a}hwiler, Beat H. and Hornung, Jean-Pierre P. and Moln{\'a}r, Zolt{\'a}n}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Research Support, Non-U.S. Gov't;Comparative Study;Rats;Pyramidal Cells;Gene Expression Regulation;Rats, Wistar;Neurofilament Proteins;Animals;23 Technique}, Month = {11}, Nlm_Id = {9110718}, Number = {11}, Organization = {Department of Human Anatomy and Genetics, University of Oxford, South Park Road, Oxford, OX1 3QX, UK.}, Pages = {1276-86}, Pii = {bhh089}, Pubmed = {15166101}, Title = {Selective neurofilament (SMI-32, FNP-7 and N200) expression in subpopulations of layer V pyramidal neurons in vivo and in vitro}, Uuid = {FC8143CD-D31C-11D9-A0E9-000D9346EC2A}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh089}} @article{Vogt:2005, Abstract = {Recent studies have identified a new family of gap junction-forming proteins in vertebrates, called pannexins. Although their function in vivo is still not known, studies in Xenopus oocytes have indicated that pannexin1 (Px1) and pannexin2 (Px2) can form functional gap junction channels and can contribute to functional hemichannels. In this study, we have utilized a combination of radioactive and non-radioactive in situ hybridization experiments to characterize the expression pattern of the two pannexin genes during development and maturation of the rat brain. Expression analysis revealed a widespread and similar mRNA distribution for both genes, but indicated that Px1 and Px2 are inversely regulated during the development of the rat brain. Px1 is expressed at a high level in the embryonic and young postnatal brain and declines considerably in the adult, whereas Px2 mRNA is low in the prenatal brain but increases substantially during subsequent postnatal development. Immunohistochemical studies using different antibodies confirm the neuronal origin of pannexin-expressing cells and ascertain the presence of both pannexins in the majority of pyramidal cells and in GABAergic interneurons. The abundant presence of both pannexins in most neurons suggests that they may play a role in intercellular communication in many neuronal circuits. Furthermore, the temporal difference in the expression of the two genes indicates that the relative contribution of the two pannexins in immature and mature neuronal circuits may vary.}, Author = {Vogt, Angelika and Hormuzdi, Sheriar G. and Monyer, Hannah}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0169-328X}, Journal = {Brain Res Mol Brain Res}, Keywords = {Aging;Gene Expression Regulation, Developmental;research support, non-u.s. gov't;Immunohistochemistry;Nerve Tissue Proteins;Parvalbumins;Rats;Rats, Wistar;Animals;Brain;Mice;RNA, Messenger;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8908640}, Number = {1}, Organization = {Department of Clinical Neurobiology, Interdisciplinary Center for Neuroscience, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.}, Pages = {113-20}, Pii = {S0169-328X(05)00323-2}, Pubmed = {16143426}, Title = {Pannexin1 and Pannexin2 expression in the developing and mature rat brain}, Uuid = {B6613570-1E35-4CA2-8E1E-1C6D14F7ABF5}, Volume = {141}, Year = {2005}, url = {papers/Vogt_BrainResMolBrainRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.molbrainres.2005.08.002}} @article{Voigt:2001, Abstract = {Neurons dissociated from embryonic cerebral rat cortex form a differentiated network of synaptic connections and develop synchronous oscillatory network activity with the beginning of the second week in culture. During an initial phase lasting 3-4 d, synchronous calcium transients can be blocked completely by either CNQX or bicuculline, showing that both glutamatergic and GABAergic neurons are required for the generation of this form of activity. By manipulating dissociation and growth conditions, cultures containing different populations of GABAergic neurons were obtained. These cultures revealed that a distinct population of large GABAergic neurons is a key element in the generation of synchronous oscillatory network activity. A minimal number of two large GABAergic neurons per square millimeter are required for the occurrence of synchronous activity. Changes in the density of all other types of GABAergic or non-GABAergic neurons has no influence on the synchronous activity. Electron microscopic analysis shows that the large GABAergic neurons form an interconnected network. Exceptionally high somatodendritic innervation and extended axonal arborization enable these neurons to collect electric network activity and to distribute it effectively throughout the neuronal network. Additional experiments indicated that most neurons developing in culture to large GABAergic neurons are derived from the primordial plexiform layer and reside in the subplate at the time of birth. We suggest that they function as an integrating element that synchronizes neuronal activity during early cortical development by collecting incoming extrinsic and intrinsic signals and distributing them effectively throughout the developing cortical plate.}, Author = {Voigt, T. and Opitz, T. and de Lima, A. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;gamma-Aminobutyric Acid;Calcium Signaling;Animals;Cells, Cultured;Rats;Glutamic Acid;Synaptic Transmission;Cell Count;Rats, Sprague-Dawley;Periodicity;Serine Endopeptidases;Receptors, Nerve Growth Factor;Biological Clocks;Cell Adhesion Molecules, Neuronal;research support, non-u.s. gov't ;Extracellular Matrix Proteins;Cell Lineage;Nerve Net;Cerebral Cortex;21 Neurophysiology;Neurons;Receptor, Nerve Growth Factor;21 Activity-development;GABA Antagonists;21 Cortical oscillations;24 Pubmed search results 2008;Nerve Tissue Proteins;GABA Agonists}, Month = {11}, Nlm_Id = {8102140}, Number = {22}, Organization = {Otto-von-Guericke Universit{\"a}t, Medizinische Fakult{\"a}t, Institut f{\"u}r Physiologie, 39120 Magdeburg, Germany. Thomas.Voigt\@Medizin.Uni-Magdeburg.de}, Pages = {8895-905}, Pii = {21/22/8895}, Pubmed = {11698601}, Title = {Synchronous oscillatory activity in immature cortical network is driven by GABAergic preplate neurons}, Uuid = {27245ED5-8061-4C0D-A154-80D604729D75}, Volume = {21}, Year = {2001}, url = {papers/Voigt_JNeurosci2001.pdf}} @article{Voyvodic:1996, Abstract = {0896-6273 Journal Article Review Review, Tutorial}, Author = {Voyvodic, J. T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:12:00 -0400}, Journal = {Neuron}, Keywords = {*Cell Death;Cerebral Cortex/cytology/embryology/*growth &development;10 Development;Cell Division;Cell Survival;Animals;F pdf}, Number = {4}, Organization = {Radiology Department, University of Pittsburgh, Pennsylvania 15213, USA.}, Pages = {693-6}, Title = {Cell death in cortical development: How much? Why? So what?}, Uuid = {BFFBE623-7B96-4CB0-A65E-1F632F75E577}, Volume = {16}, Year = {1996}, url = {papers/Voyvodic_Neuron1996.pdf}} @article{Vyazovskiy:2008, Abstract = {Plastic changes occurring during wakefulness aid in the acquisition and consolidation of memories. For some memories, further consolidation requires sleep, but whether plastic processes during wakefulness and sleep differ is unclear. We show that, in rat cortex and hippocampus, GluR1-containing AMPA receptor (AMPAR) levels are high during wakefulness and low during sleep, and changes in the phosphorylation states of AMPARs, CamKII and GSK3beta are consistent with synaptic potentiation during wakefulness and depression during sleep. Furthermore, slope and amplitude of cortical evoked responses increase after wakefulness, decrease after sleep and correlate with changes in slow-wave activity, a marker of sleep pressure. Changes in molecular and electrophysiological indicators of synaptic strength are largely independent of the time of day. Finally, cortical long-term potentiation can be easily induced after sleep, but not after wakefulness. Thus, wakefulness appears to be associated with net synaptic potentiation, whereas sleep may favor global synaptic depression, thereby preserving an overall balance of synaptic strength.}, Author = {Vyazovskiy, Vladyslav V. and Cirelli, Chiara and Pfister-Genskow, Martha and Faraguna, Ugo and Tononi, Giulio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {9809671}, Number = {2}, Organization = {[1] Department of Psychiatry, University of Wisconsin-Madison, 6001 Research Park Blvd., Madison, Wisconsin 53719, USA. [2] These authors contributed equally to this work.}, Pages = {200-8}, Pii = {nn2035}, Pubmed = {18204445}, Title = {Molecular and electrophysiological evidence for net synaptic potentiation in wake and depression in sleep}, Uuid = {B736C663-BB5E-4845-941E-AC51B3DB103C}, Volume = {11}, Year = {2008}, url = {papers/Vyazovskiy_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn2035}} @article{Wachowiak:2001, Abstract = {To visualize odorant representations by receptor neuron input to the mouse olfactory bulb, we loaded receptor neurons with calcium-sensitive dye and imaged odorant-evoked responses from their axon terminals. Fluorescence increases reflected activation of receptor neuron populations converging onto individual glomeruli. We report several findings. First, five glomeruli were identifiable across animals based on their location and odorant responsiveness; all five showed complex response specificities. Second, maps of input were chemotopically organized at near-threshold concentrations but, at moderate concentrations, involved many widely distributed glomeruli. Third, the dynamic range of input to a glomerulus was greater than that reported for individual receptor neurons. Finally, odorant activation slopes could differ across glomeruli, and for different odorants activating the same glomerulus. These results imply a high degree of complexity in odorant representations at the level of olfactory bulb input.}, Author = {Wachowiak, M. and Cohen, L. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {4}, Organization = {Department of Cellular and Molecular Physiology, Yale University School of Medicine, 06520, New Haven, CT, USA}, Pages = {723-35.}, Title = {Representation of odorants by receptor neuron input to the mouse olfactory bulb}, Uuid = {7DDDA35F-289A-4EC1-8D87-95DDEC11F019}, Volume = {32}, Year = {2001}, eprint = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11719211}} @article{Waclaw:2006, Abstract = {The molecular mechanisms that regulate the production and diversity of olfactory bulb interneurons remain poorly understood. With the exception of the GABAergic/dopaminergic subtype in the glomerular layer, no information exists concerning the generation of the other subtypes. Here we show that the recently identified zinc finger transcription factor Sp8 is expressed in neurogenic regions, which give rise to olfactory bulb interneurons at embryonic and postnatal time points and remains expressed in the calretinin-expressing and GABAergic/nondopaminergic interneurons of the glomerular layer. Conditional inactivation of Sp8 in the embryonic ventral telencephalon reveals a requirement for the normal generation of these interneuron subtypes. Sp8 conditional mutants exhibit an increase in cell death within the lateral ganglionic eminence and rostral migratory stream. Moreover, mutant neuroblasts/interneurons are misspecified and display abnormal migration patterns in the olfactory bulb, indicating that Sp8 contributes to olfactory bulb interneuron diversity by regulating the survival, migration, and molecular specification of neuroblasts/interneurons.}, Author = {Waclaw, Ronald R. and Allen, Zegary J. and Bell, Sheila M. and Erd{\'e}lyi, Ferenc and Szab{\'o}, G{\'a}bor and Potter, S. Steven and Campbell, Kenneth}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {02 Adult neurogenesis migration;24 Pubmed search results 2008;13 Olfactory bulb anatomy}, Month = {2}, Nlm_Id = {8809320}, Number = {4}, Organization = {Division of Developmental Biology, Department of Pediatrics, Children's Hospital Medical Center, University of Cincinnati College of Medicine, 3333 Burnet Avenue, Cincinnati, Ohio 45229.}, Pages = {503-16}, Pii = {S0896-6273(06)00047-X}, Pubmed = {16476661}, Title = {The zinc finger transcription factor sp8 regulates the generation and diversity of olfactory bulb interneurons}, Uuid = {8867806E-A7E4-462A-92F3-72021D710E73}, Volume = {49}, Year = {2006}, url = {papers/Waclaw_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.01.018}} @article{Wadman:1993, Abstract = {In neocortical brain slices of the rat that were exposed to 50 microM picrotoxin, low-intensity stimuli evoked all-or-none epileptiform events that propagated across the slice with an average velocity of 0.07 m/s. Simultaneous recordings from pairs of electrodes, in which one was held in a constant position and the other was systematically advanced across the slice in small steps, revealed that propagation of the synchronous activity was saltatory rather than uniform. Analysis of the propagation pattern showed that local regions (< 1000 microns) of uniform velocity were separated by distinct borders. Within these regions, local propagation velocity was determined by the threshold for synchronous activation of still-smaller (< 200 microns) neuronal aggregates. Although the velocity was sensitive to physiological factors that affect the precise threshold for synchronization, the location of the borderlines between adjacent regions remained unchanged. We propose that these invariant borders reflect the details of local neuronal organization within the slice, and that the pattern of propagation of epileptiform discharge is a manifestation of the intrinsic organization of the neocortex when deprived of afferent input.}, Author = {Wadman, W. J. and Gutnick, M. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Electric Stimulation;Picrotoxin;Epilepsy;Research Support, Non-U.S. Gov't;21 Epilepsy;21 Neurophysiology;Rats;Guinea Pigs;Electrodes;Female;In Vitro;Neurons, Afferent;Male;Animals;24 Pubmed search results 2008;Cerebral Cortex;Neurons}, Medline = {93196801}, Month = {1}, Nlm_Id = {7605074}, Number = {2}, Organization = {Department of Physiology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beersheva, Israel.}, Pages = {255-62}, Pii = {0306-4522(93)90154-8}, Pubmed = {8450945}, Title = {Non-uniform propagation of epileptiform discharge in brain slices of rat neocortex}, Uuid = {DB471E96-3D24-4C61-934D-83B18DF72A00}, Volume = {52}, Year = {1993}} @article{Wagers:2004, Abstract = {Recent years have seen much excitement over the possibility that adult mammalian stem cells may be capable of differentiating across tissue lineage boundaries, and as such may represent novel, accessible, and very versatile effectors of therapeutic tissue regeneration. Yet studies proposing such "plasticity"of adult somatic stem cells remain controversial, and in general, existing evidence suggests that in vivo such unexpected transformations are exceedingly rare and in some cases can be accounted for by equally unexpected alternative explanations. 0092-8674 Journal Article}, Author = {Wagers, A. J. and Weissman, I. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Cell}, Keywords = {22 Stem cells;S pdf}, Number = {5}, Organization = {Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA. awagers\@stanford.edu}, Pages = {639-48}, Title = {Plasticity of adult stem cells}, Uuid = {F8F1B3E8-9F63-11DA-8D49-000D9346EC2A}, Volume = {116}, Year = {2004}, url = {papers/Wagers_Cell2004.pdf}} @article{Wagner:1999, Abstract = {Mounting evidence indicates that extracellular factors exert proliferative effects on neurogenetic precursors in vivo. Recently we found that systemic levels of basic fibroblast growth factor (bFGF) regulate neurogenesis in the brain of newborn rats, with factors apparently crossing the blood-brain barrier (BBB) to stimulate mitosis. To determine whether peripheral bFGF affects proliferation during adulthood, we focused on regions in which neurogenesis persists into maturity, the hippocampus and the forebrain subventricular zone (SVZ). In postnatal day 1 (P1) rats, 8 hr after subcutaneous injection (5 ng/gm body weight), bFGF increased [(3)H]thymidine incorporation 70\%in hippocampal and SVZ homogenates and elicited twofold increases in mitotic nuclei in the dentate gyrus and the dorsolateral SVZ, detected by bromodeoxyuridine immunohistochemistry. Because approximately 25\%of proliferating hippocampal cells stimulated in vivo expressed neuronal traits in culture, bFGF-induced mitosis may reflect increased neurogenesis. bFGF effects were not restricted to the perinatal period; hippocampal DNA synthesis was stimulated by peripheral factor in older animals (P7-P21), indicating the persistence of bFGF-responsive cells and activity of peripheral bFGF into late development. To begin defining underlying mechanisms, pharmacokinetic studies were performed in P28 rats; bFGF transferred from plasma to CSF rapidly, levels rising in both compartments in parallel, indicating that peripheral factor crosses the BBB during maturity. Consequently, we tested bFGF in adults; peripheral bFGF increased the number of mitotic nuclei threefold in the SVZ and olfactory tract, regions exhibiting persistent neurogenesis. Our observations suggest that bFGF regulates ongoing neurogenesis via a unique, endocrine-like pathway, potentially coordinating neuron number and body growth, and potentially providing new approaches for treating damaged brain during development and adulthood.}, Author = {Wagner, J. P. and Black, I. B. and DiCicco-Bloom, E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Neurosci}, Keywords = {C-11;Fibroblast Growth Factor, Basic/administration &dosage/*pharmacology;Hippocampus/cytology/drug effects/growth &development;Cells, Cultured;Aging;Rats;Microtubule-Associated Proteins/analysis;Thymidine/metabolism;Neurons/cytology/*drug effects;Mitosis;Animal;Rats, Sprague-Dawley;Glial Fibrillary Acidic Protein/analysis;Prosencephalon/cytology/drug effects;Cattle;Animals, Newborn;Injections, Subcutaneous;Brain/cytology/*drug effects/growth &development;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Cell Division/drug effects}, Number = {14}, Organization = {Department of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.}, Pages = {6006-16.}, Title = {Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor}, Uuid = {FD1BBD1E-0F76-4F67-B2A2-73BE3EF82AFE}, Volume = {19}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10407038%20http://www.jneurosci.org/cgi/content/full/19/14/6006%20http://www.jneurosci.org/cgi/content/abstract/19/14/6006}} @article{Wahlers:2001, Abstract = {Using retroviral vectors encoding enhanced green fluorescent protein (EGFP), we addressed to what extent expression of retroviral transgenes in hematopoietic cells depends on the multiplicity of infection (MOI) and on the half-life of the encoded protein. We show that an elevation of the MOI not only elevates the frequency of transduced cells, but also increases transgene expression levels and reduces interanimal variability in vivo (hematopoietic cells of C57BL/6J mice analyzed 13 weeks after transplantation). This suggests that the MOI has to be carefully controlled and should be adapted as desired for clinical studies when evaluating vector performance in preclinical models. The impact of protein stability is demonstrated by comparing vectors expressing EGFP or a destabilized variant with a C-terminal PEST-sequence, d2EGFP. The loss of expression with d2EGFP was more pronounced in terminally differentiated cells of the peripheral blood (>30 fold) than in progenitor cells (five- to 10-fold), indicating a stronger transcription of the retroviral promoter in progenitor cells and a predominant role of protein inheritance over de novo synthesis of transgenic protein in mature blood cells. This analysis reveals an important and differentiation-dependent contribution of protein half-life to the expression of retroviral vectors in hematopoietic cells, establishes d2EGFP as a more accurate reporter for determination of vector transcription, and also suggests that preclinical data obtained under conditions of high transduction rates or with vectors expressing stable reporter proteins require careful interpretation.}, Author = {Wahlers, A. and Schwieger, M. and Li, Z. and Meier-Tackmann, D. and Lindemann, C. and Eckert, H. G. and von Laer, D. and Baum, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {T-Lymphocytes;Transcription, Genetic;Animals;Humans;Mice, Inbred C57BL;Retroviridae;Antigens, CD34;11 Glia;Time Factors;Green Fluorescent Proteins;Genetic Vectors;Half-Life;Bone Marrow Cells;Gene Therapy;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {21214797}, Month = {3}, Nlm_Id = {9421525}, Number = {6}, Organization = {Department Cell and Virus Genetics, Heinrich-Pette-Institute, Hamburg, Germany.}, Pages = {477-86}, Pubmed = {11313827}, Title = {Influence of multiplicity of infection and protein stability on retroviral vector-mediated gene expression in hematopoietic cells}, Uuid = {8A80C570-12D8-4309-9B55-74A834F9CB2E}, Volume = {8}, Year = {2001}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/sj/gt/3301426}} @article{Wakselman:2008, Abstract = {In several brain regions, microglia actively promote neuronal apoptosis during development. However, molecular actors leading microglia to trigger death remain mostly unknown. Here, we show that, in the developing hippocampus, apoptotic neurons are contacted by microglia expressing both the integrin CD11b and the immunoreceptor DAP12. We demonstrate that developmental apoptosis decreases in mice deficient for CD11b or DAP12. In addition, function-blocking antibodies directed against CD11b decrease neuronal death when injected into wild-type neonates, but have no effect when injected into DAP12-deficient littermates. This demonstrates that DAP12 and CD11b act in converging pathways to induce neuronal death. Finally, we show that DAP12 and CD11b control the production of microglial superoxide ions, which kill the neurons. Thus, our data show that the process of developmental neuronal death triggered by microglia is similar to the elimination of pathogenic cells by the innate immune cells.}, Author = {Wakselman, Shirley and B{\'e}chade, Catherine and Roumier, Anne and Bernard, Delphine and Triller, Antoine and Bessis, Alain}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008;research support, non-u.s. gov't;Mice, Knockout;Immunity, Natural;Cell Communication;Hippocampus;Apoptosis;Mice, Mutant Strains;Adaptor Proteins, Signal Transducing;Antigens, CD11b;Microglia;Animals;Mice;Superoxides;Neurons;Receptors, Immunologic}, Month = {8}, Nlm_Id = {8102140}, Number = {32}, Organization = {Laboratoire de Biologie Cellulaire de la Synapse, Institut National de Sant{\'e} et de Recherche M{\'e}dicale, Unit{\'e} 789, 75230 Paris Cedex 05, France.}, Pages = {8138-43}, Pii = {28/32/8138}, Pubmed = {18685038}, Title = {Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor}, Uuid = {24CD4BEB-E75B-43F4-A4C6-0A03BAC6C81F}, Volume = {28}, Year = {2008}, url = {papers/Wakselman_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1006-08.2008}} @article{Walczak:2004, Abstract = {Hematopoietic progenitors are cells, which under challenging experimental conditions can develop unusual phenotypic properties, rather distant from their original mesodermal origin. As previously reported, cells derived from human umbilical cord blood (HUCB) or human bone marrow (BM) under certain in vivo or in vitro conditions can manifest neural features that resemble features of neural-derived cells, immunocytochemically and in some instances also morphologically. The present study explored how hematopoietic-derived cells would respond to neurogenic signals from the subventricular zone (SVZ) of adult and aged (6 and 16 months old) rats. The mononuclear fraction of HUCB cells was transplanted into the SVZ of immunosuppressed (single cyclosporin or three-drug treatment) animals. The triple-suppression paradigm allowed us to protect transplanted human cells within the brain and to explore further their phenotypic and migratory properties. One week after implantation, many surviving HUCB cells were located within the SVZ and the vertical limb of the rostral migratory stream (RMS). The migration of HUCB cells was restricted exclusively to the pathway leading to the olfactory bulb. In younger animals, grafted cells navigated almost halfway through the vertical limb, whereas, in the older animals, the migration was less pronounced. The overall cell survival was greater in younger animals than in older ones. Immunocytochemistry for surface CD antigen expression showed that many HUCB cells, either cultured or within the brain parenchyma, retained their hematopoietic identity. A few cells, identified by using human-specific antibodies (anti-human nuclei, or mitochondria) expressed nestin and doublecortin, markers of endogenous neural progenitors. Therefore, it is believed that the environment of the neurogenic SVZ, even in aged animals, was able to support survival, "neuralization," and migratory features of HUCB-derived cells.}, Author = {Walczak, P. and Chen, N. and Hudson, J. E. and Willing, A. E. and Garbuzova-Davis, S. N. and Song, S. and Sanberg, P. R. and Sanchez-Ramos, J. and Bickford, P. C. and Zigova, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cell Differentiation;Cerebral Ventricles;Cell Survival;Immunohistochemistry;Green Fluorescent Proteins;Luminescent Proteins;Antigens, CD45;Male;Animals;Cells, Cultured;Age Factors;Environment;Research Support, U.S. Gov't, P.H.S.;Cell Movement;Phenotype;Cell Count;Antigens, CD;Mice, Inbred C57BL;Hematopoietic Stem Cells;Tubulin;Immunosuppressive Agents;11 Glia;Multipotent Stem Cells;Antigens, Neoplasm;Blood Proteins;Comparative Study;Rats, Inbred F344;Membrane Glycoproteins;Antigens, Surface;Glial Fibrillary Acidic Protein;Indoles;Rats;Bone Marrow Cells;Avian Proteins;Mice;Research Support, Non-U.S. Gov't;Neurons;Humans;Mice, Transgenic;Cord Blood Stem Cell Transplantation}, Month = {4}, Nlm_Id = {7600111}, Number = {2}, Organization = {Center of Excellence for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, Tampa, Florida 33612, USA. pwalczak\@hsc.usf.edu}, Pages = {244-54}, Pubmed = {15048922}, Title = {Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?}, Uuid = {EBB68EBA-EC4B-479B-954F-7C8C414CA2BF}, Volume = {76}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20042}} @article{Walikonis:2000, Abstract = {Our understanding of the organization of postsynaptic signaling systems at excitatory synapses has been aided by the identification of proteins in the postsynaptic density (PSD) fraction, a subcellular fraction enriched in structures with the morphology of PSDs. In this study, we have completed the identification of most major proteins in the PSD fraction with the use of an analytical method based on mass spectrometry coupled with searching of the protein sequence databases. At least one protein in each of 26 prominent protein bands from the PSD fraction has now been identified. We found 7 proteins not previously known to be constituents of the PSD fraction and 24 that had previously been associated with the PSD by other methods. The newly identified proteins include the heavy chain of myosin-Va (dilute myosin), a motor protein thought to be involved in vesicle trafficking, and the mammalian homolog of the yeast septin protein cdc10, which is important for bud formation in yeast. Both myosin-Va and cdc10 are threefold to fivefold enriched in the PSD fraction over brain homogenates. Immunocytochemical localization of myosin-Va in cultured hippocampal neurons shows that it partially colocalizes with PSD-95 at synapses and is also diffusely localized in cell bodies, dendrites, and axons. Cdc10 has a punctate distribution in cell bodies and dendrites, with some of the puncta colocalizing with PSD-95. The results support a role for myosin-Va in transport of materials into spines and for septins in the formation or maintenance of spines.}, Author = {Walikonis, R. S. and Jensen, O. N. and Mann, M. and Provance, D. W. and Mercer, J. A. and Kennedy, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Cycle Proteins;Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization;Synapses;Spectrum Analysis, Mass;Rats;Animals;Cells, Cultured;Cloning, Molecular;23 Technique;Hippocampus;Trypsin;Immunoblotting;Dendrites;Myosin Heavy Chains;Research Support, U.S. Gov't, P.H.S.;Hydrolysis;Intermediate Filament Proteins;Neurons;DNA, Complementary;Myosin Type V;Amino Acid Sequence;Molecular Sequence Data;Peptides;Nerve Tissue Proteins;Immunohistochemistry;Research Support, Non-U.S. Gov't}, Medline = {20279991}, Month = {6}, Nlm_Id = {8102140}, Number = {11}, Organization = {Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.}, Pages = {4069-80}, Pii = {20/11/4069}, Pubmed = {10818142}, Title = {Identification of proteins in the postsynaptic density fraction by mass spectrometry}, Uuid = {AE4284FC-F0CF-11DA-83A9-000D9346EC2A}, Volume = {20}, Year = {2000}} @article{Walker:1999, Abstract = {The brain contains two populations of macrophages: the microglia of brain parenchyma, and the central nervous system (CNS) macrophages located in the perivascular spaces, the leptomeninges and the choroid plexus. The microglia are characterized, in part, by their paucity of major histocompatibility complex (MHC) molecules and lack of constitutive antigen (Ag)-presenting activity for na{\"\i}ve CD4+ T-cells. Some CNS macrophages, on the other hand, constitutively express MHC molecules and present Ag to na{\"\i}ve CD4+ T-cells. We have reported that mouse brain contains precursor cells that, in the presence of colony-stimulating factor-1, the macrophage growth factor, give rise to clones of cells that differ in their ability to constitutively present Ag to naive CD4+ T cells. Here we report that this population of precursor cells can be separated into two discrete subpopulations based on differences in cell density and that the two cell populations give rise to progeny that differ in their content of cells constitutively expressing MHC class II and CD86 molecules, and the ability to present Ag to na{\"\i}ve CD4+ T-cells. A comparison of the level of CD45 staining of the progeny, an indication of a microglial or a CNS macrophage origin, suggests that one population of precursor cells yields immunologically immature microglia and the other CNS macrophages.}, Author = {Walker, W. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Neuroimmunomodulation;Antigens, CD45;Animals;Cell Separation;Macrophages;Brain;Microglia;Mice, Inbred C3H;Antigens, CD;Mice, Transgenic;11 Glia;Immunophenotyping;Research Support, U.S. Gov't, P.H.S.;Membrane Glycoproteins;Antibodies, Monoclonal;Antigen Presentation;Hematopoietic Stem Cells;CD4-Positive T-Lymphocytes;Mice;Clone Cells;Spleen;Histocompatibility Antigens Class II;Research Support, Non-U.S. Gov't}, Medline = {99303438}, Month = {2}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA. bill.walker\@st.jude.org}, Pages = {127-33}, Pubmed = {10376945}, Title = {Separate precursor cells for macrophages and microglia in mouse brain: immunophenotypic and immunoregulatory properties of the progeny}, Uuid = {323F4DB7-5239-4E0A-8F72-031FDB5CE398}, Volume = {94}, Year = {1999}} @article{Walker:2007, Abstract = {Doublecortin (DCX) has recently been promulgated as a selective marker of cells committed to the neuronal lineage in both the developing and the adult brain. To explore the potential of DCX-positive (DCX+) cells more stringently, these cells were isolated by flow cytometry from the brains of transgenic mice expressing green fluorescent protein under the control of the DCX promoter in embryonic, early postnatal, and adult animals. It was found that virtually all of the cells (99.9\%) expressing high levels of DCX (DCX(high)) in the embryonic brain coexpressed the neuronal marker betaIII-tubulin and that this population contained no stem-like cells as demonstrated by lack of neurosphere formation in vitro. However, the DCX+ population from the early postnatal brain and the adult subventricular zone and hippocampus, which expressed low levels of DCX (DCX(low)), was enriched for neurosphere-forming cells, with only a small subpopulation of these cells coexpressing the neuronal markers betaIII-tubulin or microtubule-associated protein 2. Similarly, the DCX(low) population from embryonic day 14 (E14) brain contained neurosphere-forming cells. Only the postnatal cerebellum and adult olfactory bulb contained some DCX(high) cells, which were shown to be similar to the E14 DCX(high) cells in that they had no stem cell activity. Electrophysiological studies confirmed the heterogeneous nature of DCX+ cells, with some cells displaying characteristics of immature or mature neurons, whereas others showed no neuronal characteristics whatsoever. These results indicate that DCX(high) cells, regardless of location, are restricted to the neuronal lineage or are bone fide neurons, whereas some DCX(low) cells retain their multipotentiality.}, Author = {Walker, Tara L. and Yasuda, Takahiro and Adams, David J. and Bartlett, Perry F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;02 Adult neurogenesis migration;research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.}, Pages = {3734-42}, Pii = {27/14/3734}, Pubmed = {17409237}, Title = {The doublecortin-expressing population in the developing and adult brain contains multipotential precursors in addition to neuronal-lineage cells}, Uuid = {ECF0D1B3-7FC5-4B75-87DD-D16C57475BE2}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5060-06.2007}} @article{Wallach:2008, Abstract = {Biological systems often change their responsiveness when subject to persistent stimulation, a phenomenon termed adaptation. In neural systems, this process is often selective, allowing the system to adapt to one stimulus while preserving its sensitivity to another. In some studies, it has been shown that adaptation to a frequent stimulus increases the system's sensitivity to rare stimuli. These phenomena were explained in previous work as a result of complex interactions between the various subpopulations of the network. A formal description and analysis of neuronal systems, however, is hindered by the network's heterogeneity and by the multitude of processes taking place at different time-scales. Viewing neural networks as populations of interacting elements, we develop a framework that facilitates a formal analysis of complex, structured, heterogeneous networks. The formulation developed is based on an analysis of the availability of activity dependent resources, and their effects on network responsiveness. This approach offers a simple mechanistic explanation for selective adaptation, and leads to several predictions that were corroborated in both computer simulations and in cultures of cortical neurons developing in vitro. The framework is sufficiently general to apply to different biological systems, and was demonstrated in two different cases.}, Author = {Wallach, and Eytan, and Marom, and Meir,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1553-7358}, Journal = {PLoS Comput Biol}, Keywords = {20 Networks;09 Evolutionary dynamics;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {101238922}, Number = {2}, Pages = {e29}, Pii = {07-PLCB-RA-0455}, Pubmed = {18282084}, Title = {Selective Adaptation in Networks of Heterogeneous Populations: Model, Simulation, and Experiment}, Uuid = {910EC162-FADB-47DD-A1C2-3E917E392DC9}, Volume = {4}, Year = {2008}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pcbi.0040029}} @article{Walsh:1998, Author = {Walsh, C. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1061-4036}, Journal = {Nat Genet}, Keywords = {Mice;Microtubule-Associated Proteins;Proteins;Mice, Knockout;10 Development;21 Neurophysiology;21 Dysplasia-heterotopia;24 Pubmed search results 2008;Abnormalities, Multiple;comment;1-Alkyl-2-acetylglycerophosphocholine Esterase;Animals;Disease Models, Animal;Cerebral Cortex;Humans;news}, Month = {8}, Nlm_Id = {9216904}, Number = {4}, Pages = {307-8}, Pubmed = {9697681}, Title = {LISsen up!}, Uuid = {9A52B650-A150-411B-8F7E-D0CEDCFFD70C}, Volume = {19}, Year = {1998}, url = {papers/Walsh_NatGenet1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/1186}} @article{Walsh:1992, Abstract = {The cerebral cortex of the mammalian brain has expanded rapidly during the course of evolution and acquired structurally distinguishable areas devoted to separate functions. In some brain regions, topographic restrictions to cell intermixing occur during embryonic development. As a means of examining experimentally whether such restrictions occur during formation of functional subdivisions in the rat neocortex, clonally related neocortical cells were marked by retroviral-mediated transfer of a histochemical marker gene. Clonal boundaries were determined by infection of the developing brain with a library of genetically distinct viruses and amplification of single viral genomes by the polymerase chain reaction. Many clonally related neurons in the cerebral cortex became widely dispersed across functional areas of the cortex. Specification of cortical areas therefore occurs after neurogenesis. 92132547 0036-8075 Journal Article}, Author = {Walsh, C. and Cepko, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Science}, Keywords = {Retroviridae/genetics;Clone Cells;Base Sequence;10 Development;Molecular Sequence Data;Rats;Cerebral Cortex/*cytology/embryology;Oligonucleotides/chemistry;Animal;Neurons/*cytology;F;Support, U.S. Gov't, P.H.S.;Brain Mapping;Support, Non-U.S. Gov't;Polymerase Chain Reaction;Genetic Vectors}, Number = {5043}, Organization = {Department of Genetics, Harvard Medical School, Boston, MA 02115.}, Pages = {434-40}, Pubmed = {1734520}, Title = {Widespread dispersion of neuronal clones across functional regions of the cerebral cortex}, Uuid = {5019B639-1B0C-4D1B-AF66-5EBCF2822B39}, Volume = {255}, Year = {1992}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1734520}} @article{Walton:2006, Abstract = {Microglia are increasingly implicated as a source of non-neural regulation of postnatal neurogenesis and neuronal development. To evaluate better the contributions of microglia to neural stem cells (NSCs) of the subventricular neuraxis, we employed an adherent culture system that models the continuing proliferation and differentiation of the dissociated neuropoietic subventricular tissues. In this model, neuropoietic cells retain the ability to self-renew and form multipotent neurospheres, but progressively lose the ability to generate committed neuroblasts with continued culture. Neurogenesis in highly expanded NSCs can be rescued by coculture with microglial cells or microglia-conditioned medium, indicating that microglia provide secreted factor(s) essential for neurogenesis, but not NSC maintenance, self-renewal, or propagation. Our findings suggest an instructive role for microglial cells in contributing to postnatal neurogenesis in the largest neurogenic niche of the mammalian brain. (c) 2006 Wiley-Liss, Inc.}, Author = {Walton, and Sutter, and Laywell, and Levkoff, and Kearns, and Marshall, and Scheffler, and Steindler,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {14 Immune;11 Glia;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8806785}, Number = {8}, Organization = {Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, Florida.}, Pages = {815-825}, Pubmed = {16977605}, Title = {Microglia instruct subventricular zone neurogenesis}, Uuid = {BC51FD76-894E-4B57-AF26-AC0304A877FD}, Volume = {54}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20419}} @article{Wang:1997, Abstract = {Glutamate metabotropic receptor mediated mechanisms have been implicated in both neuroprotection and neurotoxicity. To characterize these mechanisms further in vivo, the effects of an intrastriatally injected metabotropic receptor agonist, trans-(1S,3R)-1-amino-1,3- cyclopentanedicarboxylic acid (1S,3R-ACPD), were studied alone and together with N-methyl-D-aspartate (NMDA) or kainic acid (KA) receptor agonists on DNA fragmentation and nerve cell death. 1S,3R-ACPD induced internucleosomal DNA fragmentation of striatal cells in a dose- dependent manner. TUNEL and propidium iodide staining showed DNA fragmentation and profound nuclear condensation around the injection site. Fragmented nuclei were occasionally seen under light microscopy. Internucleosomal DNA fragmentation induced by 1S,3R-ACPD was attenuated by the protein synthesis inhibitor cycloheximide as well as by the non- selective and selective metabotropic receptor antagonists L-(+)-2-amino- 3-phosphonopionic acid (L-AP3), (RS)-aminoindan-1,5-dicarboxylic acid and (RS)-alpha-methylserine-o-phosphate monophenyl ester, respectively. The 1S,3R-ACPD (100-900 nmol) induced death of striatal neurons was suggested by the reduction in NMDA and D1 dopamine receptors by up to 13\%(P <0.05) and 20\%(P <0.05) as well as by the decline in GAD67 mRNA (25\%, P <0.01) and proenkephalin mRNA levels (35\%, P <0.01). Interestingly, 1S,3R-ACPD attenuated internucleosomal DNA fragmentation induced by NMDA, but potentiated that induced by KA. These results suggest that metabotropic receptor stimulation leads to the death of striatal neurons by a mechanism having the biochemical stigmata of apoptosis. Moreover, metabotropic receptor stimulation evidently exerts opposite effects on pre- or postsynaptic mechanisms contributing to the NMDA and KA-induced apoptotic-like death of these neurons.}, Author = {Wang, Y. and Qin, Z. H. and Nakai, M. and Chase, T. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Brain Res}, Keywords = {Alanine/analogs &derivatives/pharmacology;Neurotoxins/*toxicity;Rats;Excitatory Amino Acid Antagonists/pharmacology;07 Excitotoxicity Apoptosis;Electrophoresis, Agar Gel;Animal;Rats, Sprague-Dawley;Receptors, Metabotropic Glutamate/*agonists;In Situ Hybridization;E-6;Nucleosomes/*drug effects;Cell Death/drug effects;Protein Synthesis Inhibitors/pharmacology;Cycloleucine/*analogs &derivatives/toxicity;Autoradiography;*DNA Fragmentation;Histocytochemistry/methods}, Number = {1-2}, Organization = {Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD 20892-1406, USA.}, Pages = {45-56.}, Title = {Glutamate metabotropic receptor agonist 1S,3R-ACPD induces internucleosomal DNA fragmentation and cell death in rat striatum}, Uuid = {669F7C41-F6D9-4D3C-8F11-FDCF8C3BF5FB}, Volume = {772}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9406954}} @article{Wang:2006, Abstract = {Cortical representations of visual information are modified by an animal's visual experience. To investigate the mechanisms in mice, we replaced the coding part of the neural activity-regulated immediate early gene Arc with a GFP gene and repeatedly monitored visual experience-induced GFP expression in adult primary visual cortex by in vivo two-photon microscopy. In Arc-positive GFP heterozygous mice, the pattern of GFP-positive cells exhibited orientation specificity. Daily presentations of the same stimulus led to the reactivation of a progressively smaller population with greater reactivation reliability. This adaptation process was not affected by the lack of Arc in GFP homozygous mice. However, the number of GFP-positive cells with low orientation specificity was greater, and the average spike tuning curve was broader in the adult homozygous compared to heterozygous or wild-type mice. These results suggest a physiological function of Arc in enhancing the overall orientation specificity of visual cortical neurons during the post-eye-opening life of an animal.}, Author = {Wang, Kuan Hong and Majewska, Ania and Schummers, James and Farley, Brandon and Hu, Chengcheng and Sur, Mriganka and Tonegawa, Susumu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Heterozygote;Photic Stimulation;Animals;Mice;Mutant Strains;Visual Pathways;comparative study ;Green Fluorescent Proteins;Orientation;Mice, Knockout;21 Neurophysiology;Homozygote;Microscopy;Fluorescence;Multiphoton;Mice;Visual Cortex;Nerve Tissue Proteins;Cytoskeletal Proteins;Immediate-Early;genes;experience dependent plasticity;visual cortex;visual system;optical physiology;optical imaging;structural remodeling;refinement;axons;vision;function;frontiers review}, Month = {7}, Nlm_Id = {0413066}, Number = {2}, Organization = {Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, Pages = {389-402}, Pii = {S0092-8674(06)00860-9}, Pubmed = {16873068}, Title = {In vivo two-photon imaging reveals a role of arc in enhancing orientation specificity in visual cortex}, Uuid = {115D62C7-3557-4D43-80FA-88D337767A2D}, Volume = {126}, Year = {2006}, url = {papers/Wang_Cell2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2006.06.038}} @article{Wang:2002, Abstract = {Anatomical, electrophysiological and molecular diversity of basket cell-like interneurons in layers II-IV of rat somatosensory cortex were studied using patch-clamp electrodes filled with biocytin. This multiparametric study shows that neocortical basket cells (BCs) are composed of three distinct subclasses: classical large (LBC) and small (SBC) basket cells and a third subclass, the nest basket cell (NBC). Anatomically, NBCs were distinct from LBCs and SBCs in that they formed simpler dendritic arbors and an axonal plexus of inter-mediate density, composed of a few long, smooth axonal branches. Electrophysiologically, NBCs exhibited diverse discharge responses to depolarizing current injections including accommodation, non-accommodation and stuttering. Single-cell multiplex RT-PCR revealed distinct mRNA expression patterns for the calcium binding proteins parvalbumin (PV), calbindin (CB) and calretinin (CR), and the neuropeptides somatostatin (SOM), vasoactive intestinal peptide (VIP), cholecystokinin (CCK) and neuropeptide Y (NPY) for each BC-subclass. SBCs lacked NPY expression but invariably expressed VIP, whereas neither VIP, CR nor SOM expression was detected in LBCs, and VIP and CR expression was absent in NBCs. Electro-physiologically distinct types of NBCs formed GABAergic synapses with specific dynamics onto pyramidal cells (PCs) and received either strongly facilitating or depressing synaptic inputs from PCs. Finally, NBCs were found to be the most common basket cell in layers II/III, while LBCs were the most common in layer IV. These data provide multiparametric distinguishing features of three major subclasses of basket cells and indicate that NBCs are powerful interneurons that provide most of the (peri-)somatic inhibition in the supragranular layers.}, Author = {Wang, Yun and Gupta, Anirudh and Toledo-Rodriguez, Maria and Wu, Cai Zhi and Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Electrophysiology;Lysine;Synapses;Animals;Image Processing, Computer-Assisted;Rats;Research Support, U.S. Gov't, Non-P.H.S.;Patch-Clamp Techniques;Cytoplasm;Pyramidal Cells;Rats, Wistar;RNA, Messenger;Male;Reverse Transcriptase Polymerase Chain Reaction;21 Neurophysiology;Calcium-Binding Proteins;Membrane Potentials;Somatosensory Cortex;Interneurons;24 Pubmed search results 2008;Microscopy, Electron;Research Support, Non-U.S. Gov't}, Medline = {21881435}, Month = {4}, Nlm_Id = {9110718}, Number = {4}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06520-8001, USA.}, Pages = {395-410}, Pubmed = {11884355}, Title = {Anatomical, physiological, molecular and circuit properties of nest basket cells in the developing somatosensory cortex}, Uuid = {67708DD8-C9ED-43D1-8B8E-0AAFB55094F5}, Volume = {12}, Year = {2002}} @article{Wang:2007, Abstract = {Human type 1 lissencephaly is a severe brain malformation associated with cognitive dysfunction and intractable epilepsy. Mutant mice with a heterozygous deletion of LIS1 show varying degrees of hippocampal abnormality and enhanced excitability. Whether a reduction of LIS1 function affects adult hippocampal neurogenesis, and if so, whether aberrant neurogenesis contributes to the generation of a disorganized hippocampus remain unknown. Previous reports indicate the presence of multiple pyramidal cell layers and granule cell dispersion in LIS1 mutant mice. Here we observed disruption of the subgranular zone and glial fibrillary acidic protein-immunoreactive radial astrocytes in the dentate gyrus of adult LIS1 mice. Using pulse-chase bromodeoxyuridine (BrdU) labeling combined with neuronal and glial antibody staining we provide evidence for ectopic adult neurogenesis in LIS1 mice. A gradually decreased survival rate for these newborn granule cells was also demonstrated in LIS1 mice 7 days after BrdU injection. This reduced survival rate was associated with impaired neuronal differentiation 28 days after BrdU administration. Thus, LIS1 haploinsufficiency can lead to abnormal cell proliferation, migration and differentiation in the adult dentate gyrus.}, Author = {Wang, Yanling and Baraban, Scott C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {24 Pubmed search results 2008}, Nlm_Id = {7809375}, Number = {1-2}, Organization = {Epilepsy Research Laboratory in the Department of Neurological Surgery and PIBS Graduate Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA.}, Pages = {91-8}, Pii = {DNE20070291_2091}, Pubmed = {17148952}, Title = {Granule cell dispersion and aberrant neurogenesis in the adult hippocampus of an LIS1 mutant mouse}, Uuid = {78F60B17-E715-45E1-913B-611694FD8901}, Volume = {29}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000096214}} @article{Wang:1996, Abstract = {The present study examined the expression of different antigens in amoeboid microglial cells (AMC) in fetal rat brain extending from 12 to 20 d postconception (E12-E20) using a panel of monoclonal antibodies which recognised the major histocompatibility complex (MHC) class I (OX-18) and class II (OX-6) antigens, leucocyte common antigen (OX-1), CD4 receptor (OX-35), complement type 3 receptor (OX-42) or macrophage antigens of unknown function (ED1 and ED2). Of the above-mentioned antigens, ED1 and ED2-labelled AMC were observed in the neuroepithelia as early as embryonic day 12 (E12); other antigens were not detected at this stage. At E14, except for MHC class I antigen, all other antigens were expressed by AMC distributed predominantly in the developing white matter. At E16, AMC in the intermediate zone lateral to the striatum were endowed with all the above-mentioned antigens including MHC class I. At E18, the immunoreactivities of AMC stained with OX-6, OX-18, OX-35 and OX-42 antigens were noticeably reduced when compared with those cells at E16. At E20, amoeboid microglial cells exhibited full complement of antigen expression similar to those cells at E16; some of the labelled cells emitted a variable number of cytoplasmic processes. It is suggested that the successive and differential expression of various macrophage related antigens on AMC in fetal brain is related to the specific requirement of local environment in different stages of development.}, Author = {Wang, C. C. and Wu, C. H. and Shieh, J. Y. and Wen, C. Y. and Ling, E. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0021-8782}, Journal = {J Anat}, Keywords = {Gestational Age;Immunophenotyping;Rats;Macrophage-1 Antigen;Histocompatibility Antigens Class II;Not relevant;Antigens, CD45;Antigens;11 Glia;Antigens, CD4;Macrophages;Microglia;Histocompatibility Antigens Class I;Support, Non-U.S. Gov't;Brain;Animals;G}, Medline = {97137495}, Month = {12}, Nlm_Id = {0137162}, Organization = {Department of Anatomy, College of Medicine, National Taiwan University, Taipei.}, Pages = {567-74}, Pubmed = {8982832}, Title = {Immunohistochemical study of amoeboid microglial cells in fetal rat brain}, Uuid = {6B98C3D3-EE25-11DA-8605-000D9346EC2A}, Volume = {189 ( Pt 3)}, Year = {1996}} @article{Wang:2003, Abstract = {Previous studies have reported the presence of neuronal progenitors in the subventricular zone (SVZ) and rostral migratory stream (RMS) of the postnatal mammalian brain. Although many studies have examined the survival and migration of progenitors after transplantation and the factors influencing their proliferation or differentiation, no information is available on the electrophysiological properties of these progenitors in a near-intact environment. Thus we performed whole cell and cell-attached patch-clamp recordings of progenitors in brain slices containing either the SVZ or the RMS from postnatal day 15 to day 25 mice. Both regions displayed strong immunoreactivity for nestin and neuron-specific class III beta-tubulin, and recorded cells displayed a morphology typical of the neuronal progenitors known to migrate throughout the SVZ and RMS to the olfactory bulb. Recorded progenitors had depolarized zero-current resting potentials (mean more depolarized than -28 mV), very high input resistances (about 4 GOmega), and lacked action potentials. Using the reversal potential of K+ currents through a cell-attached patch a mean resting potential of -59 mV was estimated. Recorded progenitors displayed Ca2+-dependent K+ currents and TEA-sensitive-delayed rectifying K+ (KDR) currents, but lacked inward K+ currents and transient outward K+ currents. KDR currents displayed classical kinetics and were also sensitive to 4-aminopyridine and alpha-dendrotoxin, a blocker of Kv1 channels. Na+ currents were found in about 60\%of the SVZ neuronal progenitors. No developmental changes were observed in the passive membrane properties and current profile of neuronal progenitors. Together these data suggest that SVZ neuronal progenitors display passive membrane properties and an ionic signature distinct from that of cultured SVZ neuronal progenitors and mature neurons. 0022-3077 Journal Article}, Author = {Wang, D. D. and Krueger, D. D. and Bordey, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {J Neurophysiol}, Keywords = {Lateral Ventricles/drug effects/*growth &development;01 Adult neurogenesis general;Stem Cells/drug effects/*physiology;Support, U.S. Gov't, P.H.S.;Neurons/drug effects/*physiology;Animals, Newborn;Ion Channels/physiology;In Vitro;Biophysics;Corpus Striatum/drug effects/*growth &development;Calcium/pharmacology/physiology;Corpus Callosum/drug effects/*growth &development;Support, Non-U.S. Gov't;Animals;Mice;A pdf}, Number = {4}, Organization = {Department of Neurosurgery and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.}, Pages = {2291-302}, Pubmed = {12801891}, Title = {Biophysical properties and ionic signature of neuronal progenitors of the postnatal subventricular zone in situ}, Uuid = {67D1AD48-4093-4DAB-90E2-0865A87749B5}, Volume = {90}, Year = {2003}, url = {papers/Wang_JNeurophysiol2003.pdf}} @article{Wang:2008, Abstract = {The development of a balance between excitatory and inhibitory synapses is a critical process in the generation and maturation of functional circuits. Accumulating evidence suggests that neuronal activity plays an important role in achieving such a balance in the developing cortex, but the mechanism that regulates this process is unknown. During development, GABA, the primary inhibitory neurotransmitter in adults, excites neurons as a result of high expression of the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1). Using NKCC1 RNA interference knockdown in vivo, we show that GABA-induced depolarization is necessary for proper excitatory synapse formation and dendritic development of newborn cortical neurons. Blocking NKCC1 with the diuretic bumetanide during development leads to similar persistent changes in cortical circuitry in the adult. Interestingly, expression of a voltage-independent NMDA receptor rescues the failure of NKCC1 knockdown neurons to develop excitatory AMPA transmission, indicating that GABA depolarization cooperates with NMDA receptor activation to regulate excitatory synapse formation. Our study identifies an essential role for GABA in the synaptic integration of newborn cortical neurons and suggests an activity-dependent mechanism for achieving the balance between excitation and inhibition in the developing cortex.}, Author = {Wang, Doris D. and Kriegstein, Arnold R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {gamma-Aminobutyric Acid;Animals;Synapses;Bumetanide;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Sodium-Potassium-Chloride Symporters;Neocortex;Excitatory Amino Acid Agonists;Mutation;Mice, Transgenic;Patch-Clamp Techniques;Green Fluorescent Proteins;research support, non-u.s. gov't;Animals, Newborn;N-Methylaspartate;Neurons;Age Factors;research support, n.i.h., extramural;Mice;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Sodium Potassium Chloride Symporter Inhibitors;Excitatory Postsynaptic Potentials}, Month = {5}, Nlm_Id = {8102140}, Number = {21}, Organization = {Institute for Regeneration Medicine, University of California, San Francisco, San Francisco, California 94143, USA.}, Pages = {5547-58}, Pii = {28/21/5547}, Pubmed = {18495889}, Title = {GABA regulates excitatory synapse formation in the neocortex via NMDA receptor activation}, Uuid = {2B6CB16B-7C53-42E4-99B4-4BAB6EAC7188}, Volume = {28}, Year = {2008}, url = {papers/Wang_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5599-07.2008}} @article{Wang:1999, Abstract = {We report that neurons in the central nervous system express colony stimulating factor-1 receptor (CSF-1R) mRNA and protein and that the expression has regional specificity. The presence of CSF-1R in neurons was demonstrated by the use of four different types of antibodies to CSF-1R and the presence of CSF-1R mRNA by in situ hybridization using oligonucleotide probe. In the steady state in most areas of the brain, CSF-1R is weakly expressed in only a few neurons. In the cerebellum, brainstem, and spinal cord, however, CSF-1R is expressed constitutively in greater numbers of neurons. After cerebral cortex ischemic injury, neurons in the area next to the ischemic lesion markedly upregulate CSF-1R. It is also upregulated in the contralateral cortex and in many other areas of the brain and spinal cord. We demonstrated that in cultures the ligand CSF-1 binds to its receptor (CSF-1R) in neurons and that reduction of the number of apoptotic neurons and potentiation of neuron survival is CSF-1 dose dependent. We propose that CSF-1/CSF-1R signaling is an important regulatory pathway between neurons, microglia, and astrocytes.}, Author = {Wang, Y. and Berezovska, O. and Fedoroff, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cell Survival;Human;Animals;Gene Expression Regulation;Cells, Cultured;Recombinant Proteins;Apoptosis;Receptor, Macrophage Colony-Stimulating Factor;Mice, Inbred C3H;Translation, Genetic;Brain;RNA, Messenger;11 Glia;Male;Embryo;Spinal Cord;Support, Non-U.S. Gov't;Cerebral Cortex;Neurons;Brain Ischemia;Macrophage Colony-Stimulating Factor;Mice;Transcription, Genetic}, Medline = {99393594}, Month = {9}, Nlm_Id = {7600111}, Number = {5}, Organization = {Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.}, Pages = {616-32}, Pii = {10.1002/(SICI)1097-4547(19990901)57:5<616::AID-JNR4>3.0.CO;2-E}, Pubmed = {10462686}, Title = {Expression of colony stimulating factor-1 receptor (CSF-1R) by CNS neurons in mice}, Uuid = {EBC46FB9-09D4-4A12-9F5C-B060F9CEA961}, Volume = {57}, Year = {1999}} @article{Wang:2004, Abstract = {Whole-cell patch-clamp recordings followed by histochemical staining and single-cell RT-PCR were obtained from 180 Martinotti interneurones located in layers II to VI of the somatosensory cortex of Wistar rats (P13-P16) in order to examine their anatomical, electrophysiological and molecular properties. Martinotti cells (MCs) mostly displayed ovoid-shaped somata, bitufted dendritic morphologies, and axons with characteristic spiny boutons projecting to layer I and spreading horizontally across neighbouring columns more than 1 mm. Electron microscopic examination of MC boutons revealed that all synapses were symmetrical and most synapses (71\%) were formed onto dendritic shafts. MCs were found to contact tuft, apical and basal dendrites in multiple neocortical layers: layer II/III MCs targeted mostly layer I and to a lesser degree layer II/III; layer IV MCs targeted mostly layer IV and to a lesser degree layer I; layer V and VI MCs targeted mostly layer IV and layer I and to a lesser degree the layer in which their somata was located. MCs typically displayed spike train accommodation (90\%; n = 127) in response to depolarizing somatic current injections, but some displayed non-accommodating (8\%) and a few displayed irregular spiking responses (2\%). Some accommodating and irregular spiking MCs also responded initially with bursts (17\%). Accommodating responses were found in all layers, non-accommodating mostly in upper layers and bursting mostly in layer V. Single-cell multiplex RT-PCR performed on 63 MCs located throughout layers II-VI, revealed that all MCs were somatostatin (SOM) positive, and negative for parvalbumin (PV) as well as vasoactive intestinal peptide (VIP). Calbindin (CB), calretinin (CR), neuropeptide Y (NPY) and cholecystokinin (CCK) were co- expressed with SOM in some MCs. Some layer-specific trends seem to exist. Finally, 24 accommodating MCs were examined for the expression of 26 ion channel genes. The ion channels with the highest expression in these MCs were (from highest to lowest); Cabeta1, Kv3.3, HCN4, Cabeta4, Kv3.2, Kv3.1, Kv2.1, HCN3, Caalpha1G, Kv3.4, Kv4.2, Kv1.1 and HCN2. In summary, this study provides the first detailed analysis of the anatomical, electrophysiological and molecular properties of Martinotti cells located in different neocortical layers. It is proposed that MCs are crucial interneurones for feedback inhibition in and between neocortical layers and columns.}, Author = {Wang, Yun and Toledo-Rodriguez, Maria and Gupta, Anirudh and Wu, Caizhi and Silberberg, Gilad and Luo, Junyi and Markram, Henry}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Synapses;Ion Channels;21 Neurophysiology;Action Potentials;Rats;Neuropeptides;Rats, Wistar;Gene Expression Profiling;Cell Shape;Interneurons;Somatosensory Cortex;Age Factors;Animals;24 Pubmed search results 2008;Patch-Clamp Techniques}, Month = {11}, Nlm_Id = {0266262}, Number = {Pt 1}, Organization = {Division of Neurology Research, St. Elizabeth's Medical Center, Tufts University, Boston, MA 02135, USA.}, Pages = {65-90}, Pii = {jphysiol.2004.073353}, Pubmed = {15331670}, Title = {Anatomical, physiological and molecular properties of Martinotti cells in the somatosensory cortex of the juvenile rat}, Uuid = {4B300117-172C-40B7-B893-51C0AFB0BBC4}, Volume = {561}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1113/jphysiol.2004.073353}} @article{Wang:2006b, Abstract = {The prefrontal cortex is specially adapted to generate persistent activity that outlasts stimuli and is resistant to distractors, presumed to be the basis of working memory. The pyramidal network that supports this activity is unknown. Multineuron patch-clamp recordings in the ferret medial prefrontal cortex showed a heterogeneity of synapses interconnecting distinct subnetworks of different pyramidal cells. One subnetwork was similar to the pyramidal network commonly found in primary sensory areas, consisting of accommodating pyramidal cells interconnected with depressing synapses. The other subnetwork contained complex pyramidal cells with dual apical dendrites displaying nonaccommodating discharge patterns; these cells were hyper-reciprocally connected with facilitating synapses displaying pronounced synaptic augmentation and post-tetanic potentiation. These cellular, synaptic and network properties could amplify recurrent interactions between pyramidal neurons and support persistent activity in the prefrontal cortex.}, Author = {Wang, Yun and Markram, Henry and Goodman, Philip H. and Berger, Thomas K. and Ma, Junying and Goldman-Rakic, Patricia S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Synapses;Research Support, Non-U.S. Gov't;21 Neurophysiology;Prefrontal Cortex;Pyramidal Cells;Ferrets;In Vitro;Research Support, N.I.H., Extramural;Synaptic Transmission;Nerve Net;Animals;Patch-Clamp Techniques;Membrane Potentials;24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {9809671}, Number = {4}, Organization = {Division of Neurology Research, Caritas St. Elizabeth's Medical Center, Tufts University, Boston, Massachusetts 02135, USA. yun.wang\@tufts.edu}, Pages = {534-42}, Pii = {nn1670}, Pubmed = {16547512}, Title = {Heterogeneity in the pyramidal network of the medial prefrontal cortex}, Uuid = {737E1131-54FF-4536-87D8-1A32068A1681}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1670}} @article{Wang:1991, Abstract = {The complementary DNA sequence encoding the cell-surface receptor for ecotropic host-range murine retroviruses (ecoR) shows that it contains 622 amino acids and 14 hydrophobic potentially membrane-spanning sequences. Because this receptor occurs on many or all murine cells and is probably essential for viability of cultured fibroblasts, its normal function might be to transport an essential metabolite. We expressed ecoR in Xenopus laevis oocytes by injecting RNA transcribed from the cloned cDNA. These oocytes specifically bound the gp70 envelope glycoprotein from an ecotropic murine leukaemia virus. An inward current was recorded electrophysiologically when a mixture of amino-acids was applied: this resulted from a stereoselective, saturable uptake of lysine, arginine and ornithine; it was independent of sodium and not substantially altered by gp70. Cysteine and homoserine were also taken up, but sodium was necessary for their transport. These properties of ecoR correspond to those of the y+ amino-acid transporter. Our results demonstrate the subversion of a ubiquitous cell membrane protein, in this case a basic amino acid transporter, for use as a retroviral receptor.}, Author = {Wang, H. and Kavanaugh, M. P. and North, R. A. and Kabat, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Arginine;Animals;Electric Conductivity;In Vitro;Lysine;Cloning, Molecular;Cations;Biological Transport;Recombinant Proteins;15 Retrovirus mechanism;Kinetics;Xenopus laevis;Viral Envelope Proteins;Research Support, U.S. Gov't, P.H.S.;Moloney murine leukemia virus;Membrane Glycoproteins;Receptors, Virus;Membrane Transport Proteins;24 Pubmed search results 2008;Ornithine}, Medline = {91343002}, Month = {8}, Nlm_Id = {0410462}, Number = {6337}, Organization = {Department of Biochemistry, Oregon Health Sciences University, Portland 97201.}, Pages = {729-31}, Pubmed = {1908564}, Title = {Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter}, Uuid = {0B790250-EE2C-11DA-8605-000D9346EC2A}, Volume = {352}, Year = {1991}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/352729a0}} @article{Wang:2003a, Abstract = {Evidence suggests that haematopoietic stem cells might have unexpected developmental plasticity, highlighting therapeutic potential. For example, bone-marrow-derived hepatocytes can repopulate the liver of mice with fumarylacetoacetate hydrolase deficiency and correct their liver disease. To determine the underlying mechanism in this murine model, we performed serial transplantation of bone-marrow-derived hepatocytes. Here we show by Southern blot analysis that the repopulating hepatocytes in the liver were heterozygous for alleles unique to the donor marrow, in contrast to the original homozygous donor cells. Furthermore, cytogenetic analysis of hepatocytes transplanted from female donor mice into male recipients demonstrated 80,XXXY (diploid to diploid fusion) and 120,XXXXYY (diploid to tetraploid fusion) karyotypes, indicative of fusion between donor and host cells. We conclude that hepatocytes derived form bone marrow arise from cell fusion and not by differentiation of haematopoietic stem cells. 0028-0836 Journal Article}, Author = {Wang, X. and Willenbring, H. and Akkari, Y. and Torimaru, Y. and Foster, M. and Al-Dhalimy, M. and Lagasse, E. and Finegold, M. and Olson, S. and Grompe, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Nature}, Keywords = {In Situ Hybridization, Fluorescence;Cell Differentiation;Heterozygote;Animals;Hybrid Cells/*cytology/metabolism;Hematopoietic Stem Cells/*cytology;Female;EE pdf;Cell Fusion;Hepatocytes/*cytology/metabolism/*transplantation;Male;Diploidy;Support, Non-U.S. Gov't;Alleles;Homozygote;Karyotyping;Bone Marrow Cells/*cytology;Support, U.S. Gov't, P.H.S.;Polyploidy;Mice}, Number = {6934}, Organization = {Department of Molecular and Medical Genetics, Oregon Health &Science University, Portland, Oregon 97239, USA.}, Pages = {897-901}, Pubmed = {12665832}, Title = {Cell fusion is the principal source of bone-marrow-derived hepatocytes}, Uuid = {E8A87491-CEDB-11D9-B244-000D9346EC2A}, Volume = {422}, Year = {2003}, url = {../../Volumes/Vega/Users/ackman/James/Endnotelibraries/OMEGAoldpdfs/EE-aberrantcellcyclepdfs/cellfusion2-nat03.pdf}} @article{Wang:2000, Author = {Wang, S. and Barres, B. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {Cell Differentiation/*physiology;Schwann Cells/cytology;Ligands;Embryonic Induction;11 Glia;Neurons/*cytology;Cerebral Cortex/cytology/embryology/metabolism;Signal Transduction/*physiology;Neuroglia/*cytology/*metabolism;G;Membrane Proteins/metabolism;Retina/cytology/embryology/metabolism;Stem Cells/*cytology/metabolism}, Number = {2}, Organization = {Stanford University School of Medicine, Department of Neurobiology, California 94305, USA. songli\@stanford.edu}, Pages = {197-200.}, Title = {Up a notch: instructing gliogenesis}, Uuid = {CDE8488E-6408-4705-8464-ABA05E395AC0}, Volume = {27}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10985340}} @article{Wang:2001, Abstract = {Compared to neurons, the intracellular mechanisms that control glial differentiation are still poorly understood. We show here that oligodendrocyte lineage cells express the helix-loop-helix proteins Mash1 and Id2. Although Mash1 has been found to regulate neuronal development, we found that in the absence of Mash1 oligodendrocyte differentiation occurs normally. In contrast, we found that overexpression of Id2 powerfully inhibits oligodendrocyte differentiation, that Id2 normally translocates out of the nucleus at the onset of differentiation, and that absence of Id2 induces premature oligodendrocyte differentiation in vitro. These findings demonstrate that Id2 is a component of the intracellular mechanism that times oligodendrocyte differentiation and point to the existence of an as yet unidentified MyoD-like bHLH protein necessary for oligodendrocyte differentiation.}, Author = {Wang, S. and Sdrulla, A. and Johnson, J. E. and Yokota, Y. and Barres, B. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {G;Platelet-Derived Growth Factor/pharmacology;*Helix-Loop-Helix Motifs;Cells, Cultured;Rats;*Cell Differentiation;Oligodendroglia/chemistry/*cytology/metabolism;DNA-Binding Proteins/analysis/deficiency/genetics/*physiology;Transcription Factors/analysis/deficiency/physiology;Animal;11 Glia;Time Factors;RNA, Messenger/analysis;Support, Non-U.S. Gov't;Mice, Knockout;Triiodothyronine/pharmacology;Support, U.S. Gov't, P.H.S.;Polymerase Chain Reaction;Mice;Cell Division;Immunohistochemistry;Gene Expression;Optic Nerve/cytology;Stem Cells/chemistry/*cytology/metabolism}, Number = {3}, Organization = {Stanford University School of Medicine, Department of Neurobiology, Sherman Fairchild Science Building D231, 299 Campus Drive, Stanford, CA 94305, USA.}, Pages = {603-14.}, Title = {A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development}, Uuid = {F09FD640-6216-44BB-AE75-BB5D68AA545B}, Volume = {29}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11301021}} @article{Wang:2006a, Abstract = {Focal cortical dysplasia (FCD) is found in approximately one-half of patients with medically refractory epilepsy. These lesions may involve only mild disorganization of the cortex, but they may also contain abnormal neuronal elements such as balloon cells. Advances in neuroimaging have allowed better identification of these lesions, and thus more patients have become surgical candidates. Molecular biology techniques have been used to explore the genetics and pathophysiological characteristics of FCD. Data from surgical series have shown that surgery often results in significant reduction or cessation of seizures, especially if the entire lesion is resected.}, Author = {Wang, Vincent Y. and Chang, Edward F. and Barbaro, Nicholas M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1092-0684}, Journal = {Neurosurg Focus}, Keywords = {Epilepsy;Mutation;Brain Diseases;10 Development;21 Dysplasia-heterotopia;21 Neurophysiology;Treatment Outcome;Nerve Tissue Proteins;10 genetics malformation;Humans;Cerebral Cortex;review;24 Pubmed search results 2008}, Nlm_Id = {100896471}, Number = {1}, Organization = {Department of Neurological Surgery, University of California, San Francisco, California 94130, USA.}, Pages = {E7}, Pii = {200107}, Pubmed = {16459997}, Title = {Focal cortical dysplasia: a review of pathological features, genetics, and surgical outcome}, Uuid = {0FEB1B2A-A079-4713-9CBA-67BC87164208}, Volume = {20}, Year = {2006}, url = {papers/Wang_NeurosurgFocus2006.pdf}} @article{Ward:2003, Abstract = {Although neuronal migration is an essential process in development, how neural precursors reach their final destination in the nervous system is not well understood. Secreted molecules that are known to be involved in axon guidance are likely to play important roles in regulating neuronal migration, but an important issue that remains unclear is whether such molecules act as directional guidance cues or as motility regulators in neuronal migration. The secreted protein Slit was initially suggested to be a repellent for migrating neurons (Wu et al., 1999). However, it was concluded recently that Slit plays an inhibitory rather than a repulsive role in neuronal migration (Mason et al., 2001). We have developed a series of assays that allow us to differentiate between repulsive and inhibitory effects of secreted molecules, and we demonstrate that Slit is a repellent capable of reversing the direction of neurons migrating either in culture or in their native pathways. We also show that although Slit reduces migratory speed under certain conditions, it can function as a repellent without concurrent inhibition of neuronal migration. This is the first study to clearly demonstrate that migrating neurons can be directionally guided by secreted molecules. These findings provide a basis to understand the physiological roles of secreted molecules in the developing nervous system and have implications on how they could be applied therapeutically. Our results also indicate that it should be possible to determine the specific action of other molecules as directional guidance cues or as motility regulators of cell migration. 1529-2401 Journal Article}, Author = {Ward, M. and McCann, C. and DeWulf, M. and Wu, J. Y. and Rao, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {J Neurosci}, Keywords = {B pdf;Nerve Tissue Proteins/pharmacology/*physiology/secretion;02 Adult neurogenesis migration;Culture Media, Conditioned/pharmacology;Human;Cell Movement/drug effects/*physiology;Rats;Time Factors;Glycoproteins/pharmacology/*physiology/secretion;Coculture;Lateral Ventricles/cytology;Kidney/cytology/metabolism/secretion;Support, U.S. Gov't, P.H.S.;Cells, Cultured;Animals;Support, Non-U.S. Gov't;Neurons/*cytology/drug effects/*physiology}, Number = {12}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.}, Pages = {5170-7}, Pubmed = {12832541}, Title = {Distinguishing between directional guidance and motility regulation in neuronal migration}, Uuid = {7422A521-5EE1-4B8A-9B28-16D2FADC1DC5}, Volume = {23}, Year = {2003}, url = {papers/Ward_JNeurosci2003.pdf}} @article{Warner-Schmidt:2007, Abstract = {The neural mechanisms underlying the cellular and behavioral responses to antidepressants are not yet known. Up-regulation of growth factors and adult neurogenesis suggest a role for one or more of these factors in the action of antidepressants. One candidate of interest is vascular endothelial growth factor (VEGF), which was initially characterized for its role in angiogenesis, but also exerts direct mitogenic effects on neural progenitors in vitro. Results of this study demonstrate that VEGF is induced by multiple classes of antidepressants at time points consistent with the induction of cell proliferation and therapeutic action of these treatments. We find that VEGF signaling through the Flk-1 receptor is required for antidepressant-induced cell proliferation. We also show that VEGF-Flk-1 signaling is required and sufficient for behavioral responses in two chronic and two subchronic antidepressant models. Taken together, these studies identify VEGF and VEGF-Flk-1 signaling as mediators of antidepressant actions and potential targets for therapeutic intervention.}, Author = {Warner-Schmidt, Jennifer L. and Duman, Ronald S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {04 Adult neurogenesis factors;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {7505876}, Number = {11}, Organization = {Departments of Psychiatry and Pharmacology, Yale University School of Medicine, New Haven, CT 06508.}, Pages = {4647-52}, Pii = {0610282104}, Pubmed = {17360578}, Title = {VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants}, Uuid = {8AA57953-429D-4417-A1BF-F10757AB3865}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0610282104}} @article{Warren:1973, Abstract = {0008-5472 Journal Article}, Author = {Warren, J. and Sacksteder, M. R. and Ellis, B. M. and Schwartz, R. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Cancer Res}, Keywords = {Mice, Inbred BALB C;Injections, Intraperitoneal;Animals;Cells, Cultured;Virus Replication/drug effects;*Moloney murine leukemia virus/drug effects;Injections, Intramuscular;Fibroblasts;EE, DMSO, abstr;08 Aberrant cell cycle;Time Factors;Embryo;*Sarcoma Viruses, Avian/drug effects;Dimethyl Sulfoxide/*administration &dosage/pharmacology;Mice;Administration, Oral;Sarcoma, Avian/pathology;Quail;Sarcoma, Experimental/*etiology/pathology}, Number = {3}, Pages = {618-22}, Pubmed = {4347720}, Title = {Enhancement of viral oncogenicity by the prior administration of dimethyl sulfoxide}, Uuid = {4AFDA350-3E66-4344-AEA8-5CBF77023B03}, Volume = {33}, Year = {1973}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4347720}} @article{Watanabe:2002, Abstract = {A8 virus (A8-V) is a molecular clone of the neuropathogenic FrC6 virus derived from the Friend murine leukemia virus (F-MuLV). The A8-V infects endothelia and microglia in the brain. We constructed a gene transfer system with the A8-V gene. Pseudotyped virus carrying the surface protein of A8-V (A8-SU) transduced the beta-glactosidase gene incorporated in the retroviral vector efficiently to cultured microglial cells derived from newborn rats. Ex vivo gene transferred microglial cells were then injected into the right hemisphere of 3-day-old and 3-week-old rat brains. All of the rats examined at 4 weeks after the injection contained the labeled microglial cells in the brain (7/7 and 5/5 of the rats injected at 3 days and 3 weeks, respectively). None of the rats showed pathological changes in the whole body investigated, including the central nervous system, 4 weeks after transplantation of the labeled microglial cells.}, Author = {Watanabe, Rihito and Takase-Yoden, Sayaka and Fukumitsu, Hidefumi and Nakajima, Kazuyuki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0963-6897}, Journal = {Cell Transplant}, Keywords = {Research Support, Non-U.S. Gov't;Rats, Inbred Lew;Rats;Retroviridae;11 Glia;Microglia;Cells, Cultured;Brain;Animals;Genetic Vectors}, Medline = {22270118}, Nlm_Id = {9208854}, Number = {5}, Organization = {Institute of Life Science, Soka University, Hachioji, Tokyo, Japan. rihito\@t.soka.ac.jp}, Pages = {471-3}, Pubmed = {12382676}, Title = {Cell transplantation to the brain with microglia labeled by neuropathogenic retroviral vector system}, Uuid = {B7759AB5-C05D-4D4C-A3F1-AA819A161070}, Volume = {11}, Year = {2002}, url = {papers/Watanabe_CellTransplant2002.pdf}} @article{Waters:2004, Abstract = {Action potentials backpropagate into the dendritic trees of pyramidal neurons, reporting output activity to the sites of synaptic input and provoking long-lasting changes in synaptic strength. It is unclear how this retrograde signal is modified by neural network activity. Using whole-cell recordings from somata, apical trunks, and dendritic tuft branches of layer 2/3 pyramidal neurons in vivo, we show that network-driven subthreshold membrane depolarizations ("up states") occur simultaneously throughout the apical dendritic tree. This spontaneous synaptic activity enhances action potential-evoked calcium influx into the distal apical dendrite by promoting action potential backpropagation. Hence, somatic feedback to the dendrites becomes stronger with increasing network activity.}, Author = {Waters, Jack and Helmchen, Fritjof}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;Electroencephalography;Dendrites;21 Neurophysiology;Action Potentials;research support, non-u.s. gov't ;Pyramidal Cells;Rats;Calcium;Neocortex;21 Calcium imaging;Rats, Wistar;Nerve Net;Animals;21 Cortical oscillations;24 Pubmed search results 2008;Signal Processing, Computer-Assisted}, Month = {12}, Nlm_Id = {8102140}, Number = {49}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut f{\"u}r medizinische Forschung, 69120 Heidelberg, Germany. jwaters\@mpimf-heidelberg.mpg.de}, Pages = {11127-36}, Pii = {24/49/11127}, Pubmed = {15590929}, Title = {Boosting of action potential backpropagation by neocortical network activity in vivo}, Uuid = {F84326BD-35A5-4AC8-B29D-68464F9E3EAA}, Volume = {24}, Year = {2004}, url = {papers/Waters_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2933-04.2004}} @article{Waters:2006, Abstract = {Neurons are continually exposed to background synaptic activity in vivo. This is thought to influence neural information processing, but background levels of excitation and inhibition remain controversial. Here we show, using whole-cell recordings in anesthetized rats, that spontaneous depolarizations ("Up states") in neocortical pyramidal neurons are driven by sparse, mostly excitatory synaptic activity (less than five inputs per millisecond; approximately 10\%inhibitory). The mean synaptic conductance change is small (<10 nS at the soma) and opposed by anomalous rectification, resulting in a net increase in input resistance during Up states. These conditions enhance the effectiveness of each synapse at depolarized potentials. Hence, neocortical networks are relatively quiet at rest, and the effect of synaptic background is weaker than previously thought.}, Author = {Waters, Jack and Helmchen, Fritjof}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Animals;Rats;Synaptic Transmission;Neocortex;Models, Statistical;Rats, Wistar;Biological Clocks;Computer Simulation;Action Potentials;21 Neurophysiology;Neurons;Membrane Potentials;Differential Threshold;24 Pubmed search results 2008;21 Cortical oscillations;Neural Inhibition;Models, Neurological;Excitatory Postsynaptic Potentials}, Month = {8}, Nlm_Id = {8102140}, Number = {32}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut f{\"u}r Medizinische Forschung, 69120 Heidelberg, Germany. jackwaters\@northwestern.edu}, Pages = {8267-77}, Pii = {26/32/8267}, Pubmed = {16899721}, Title = {Background synaptic activity is sparse in neocortex}, Uuid = {6DD7AFA2-4CB0-40D9-ADBB-EF98D7EE40F6}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2152-06.2006}} @article{Watson:2003, Abstract = {Human Ntera-2 (NT2) cells can be differentiated in vitro into well-characterized populations of NT2N neurons that engraft and mature when transplanted into the adult CNS of rodents and humans. They have shown promise as treatments for neurologic disease, trauma, and ischemic stroke. Although these features suggest that NT2N neurons would be an excellent platform for ex vivo gene therapy in the CNS, stable gene expression has been surprisingly difficult to achieve in these cells. In this report we demonstrate stable, efficient, and nontoxic gene transfer into undifferentiated NT2 cells using a pseudotyped lentiviral vector encoding the human elongation factor 1-alpha promoter and the reporter gene eGFP. Expression of eGFP was maintained when the NT2 cells were differentiated into NT2N neurons after treatment with retinoic acid. When transplanted into the striatum of adult nude mice, transduced NT2N neurons survived, engrafted, and continued to express the reporter gene for long-term time points in vivo. Furthermore, transplantation of NT2N neurons genetically modified to express nerve growth factor significantly attenuated cognitive dysfunction following traumatic brain injury in mice. These results demonstrate that defined populations of genetically modified human NT2N neurons are a practical and effective platform for stable ex vivo gene delivery into the CNS.}, Author = {Watson, Deborah J. and Longhi, Luca and Lee, Edward B. and Fulp, Carl T. and Fujimoto, Scott and Royo, Nicolas C. and Passini, Marco A. and Trojanowski, John Q. and Lee, Virginia M. Y. and McIntosh, Tracy K. and Wolfe, John H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Cell Differentiation;Animals;Stem Cell Transplantation;Gene Expression Regulation;Nerve Growth Factor;Treatment Outcome;Rats;Recovery of Function;Humans;Research Support, U.S. Gov't, Non-P.H.S.;Lentivirus;Female;11 Glia;PC12 Cells;Green Fluorescent Proteins;Mice, Nude;Genetic Vectors;Brain Injuries;Research Support, U.S. Gov't, P.H.S.;Gene Therapy;Gene Transfer Techniques;Neurons;Mice;Peptide Elongation Factor 1;Luminescent Proteins;Graft Survival;Stem Cells;Tretinoin;Research Support, Non-U.S. Gov't}, Medline = {22606053}, Month = {4}, Nlm_Id = {2985192R}, Number = {4}, Organization = {Department of Pathobiology, Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, USA.}, Pages = {368-80}, Pubmed = {12722829}, Title = {Genetically modified NT2N human neuronal cells mediate long-term gene expression as CNS grafts in vivo and improve functional cognitive outcome following experimental traumatic brain injury}, Uuid = {493ABD0F-6F42-4FE9-BA8F-EA1DAA2382CD}, Volume = {62}, Year = {2003}} @article{Watt:2001, Abstract = {Expression of the p75 low-affinity neurotrophin receptor (p75NTR) was investigated immunocytochemically at the light and ultrastructural level during the axonal degeneration that follows partial denervation of the rat neural lobe (NL) and following systemic administration of lipopolysaccharide (LPS). A significant increase in the intensity and extent of p75NTR immunoreactivity in the NL of partially denervated animals compared with age-matched, sham-operated controls was observed at 5-10 days postdenervation, with immunoreactivity returning to control values by 35 days. Dual-label confocal comparison of p75NTR localization with that of the C3bi complement receptor, a microglial marker, and S100, an astrocyte-specific Ca2+-binding protein, revealed no colocalization. Immunoelectron-microscopic examination demonstrated that the p75NTR immunoreactivity is present in a subpopulation of cells located within the extensive perivascular space of the NL. No examples of p75NTR-immunoreactive pituicytes or endothelia were observed at the light or ultrastructural level. Dense p75NTR immunoreactivity was frequently observed surrounding endocytotic omega profiles of plasmalemma engulfing extracellular debris as well as lining vacuoles within the cytoplasm of perivascular cells. The association of p75NTR with phagocytosis was confirmed by confocal microscopy, showing the presence of p75NTR in all cells expressing the ED-1 antigen, which is restricted to the lysosomal membrane of phagocytes (Damoiseaux et al. 1994). Likewise, a marked increase in p75NTR and ED-1 immunoreactivity was observed in the NL following systemic administration of LPS. These results suggest a strong correlation between modulation of p75NTR immunoreactivity and conditions that induce high levels of phagocytic activity by perivascular cells in the NL of the rat. Implications for understanding the mechanisms by which phagocytes may support compensatory responses to neuronal injury are discussed.}, Author = {Watt, J. A. and Paden, C. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0302-766X}, Journal = {Cell Tissue Res}, Keywords = {Lysosomes;Phagocytosis;Animals;Microscopy, Immunoelectron;Up-Regulation;Rats;Microglia;Denervation;Pituitary Gland, Posterior;Rats, Sprague-Dawley;Lipopolysaccharides;Not relevant;11 Glia;Male;Receptors, Complement;Antigens;Support, U.S. Gov't, P.H.S.;Receptor, Nerve Growth Factor;Immunohistochemistry;Complement 3b;S100 Proteins}, Medline = {21130734}, Month = {1}, Nlm_Id = {0417625}, Number = {1}, Organization = {Department of Cell Biology and Neuroscience, Montana State University, Bozeman 59717-0346, USA. jwatt\@montana.edu}, Pages = {81-91}, Pubmed = {11236007}, Title = {Upregulation of the p75 low-affinity neurotrophin receptor by phagocytically active perivascular active cells in the rat neural lobe}, Uuid = {8AE248B5-5D00-4AEE-8D77-FDA67AC7510D}, Volume = {303}, Year = {2001}} @article{Watt:2004, Abstract = {Most excitatory glutamatergic synapses contain both AMPA and NMDA receptors, but whether these receptors are regulated together or independently during synaptic plasticity has been controversial. Although long-term potentiation (LTP) is thought to selectively enhance AMPA currents and alter the NMDA-to-AMPA ratio, this ratio is well conserved across synapses onto the same neuron. This suggests that the NMDA-to-AMPA ratio is only transiently perturbed by LTP. To test this, we induced LTP at rat neocortical synapses and recorded mixed AMPA-NMDA currents. We observed rapid LTP of AMPA currents, as well as delayed potentiation of NMDA currents that required previous AMPA potentiation. The delayed potentiation of NMDA currents restored the original NMDA-to-AMPA ratio within 2 h of LTP induction. These data suggest that recruitment of AMPA receptors to synapses eventually induces a proportional increase in NMDA current. This may ensure that LTP does not alter the relative contributions of these two receptors to synaptic transmission and information processing.}, Author = {Watt, Alanna J. and Sj{\"o}str{\"o}m, Per Jesper and H{\"a}usser, Michael and Nelson, Sacha B. and Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Excitatory Amino Acid Antagonists;research support, non-u.s. gov't ;24 Pubmed search results 2008;Sodium Channel Blockers;Animals;Cells, Cultured;research support, u.s. gov't, p.h.s. ;comparative study ;alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;Visual Cortex;Drug Synergism;Transfection;Electric Stimulation;Quinoxalines;Synapses;Long-Term Potentiation;research support, u.s. gov't, p.h.s.;Excitatory Amino Acid Agonists;N-Methylaspartate;comparative study;in vitro;Tetrodotoxin;Time Factors;Rats;Patch-Clamp Techniques;Receptors, AMPA;Animals, Newborn;research support, non-u.s. gov't;21 Neurophysiology;Valine;Neurons;in vitro ;Excitatory Postsynaptic Potentials}, Month = {5}, Nlm_Id = {9809671}, Number = {5}, Organization = {Department of Biology and Volen National Center for Complex Systems, MS 08, 415 South Street, Brandeis University, Waltham, Massachusetts 02454, USA.}, Pages = {518-24}, Pii = {nn1220}, Pubmed = {15048122}, Title = {A proportional but slower NMDA potentiation follows AMPA potentiation in LTP}, Uuid = {A7F5B081-074A-4749-8EB9-E2CCF6517BDD}, Volume = {7}, Year = {2004}, url = {papers/Watt_NatNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1220}} @article{Watts:2004, Abstract = {Developmental axon pruning is widely used in constructing the nervous system. Accordingly, diverse mechanisms are likely employed for various forms of axon pruning. In the Drosophila mushroom bodies (MB), gamma neurons initially extend axon branches into both the dorsal and medial MB axon lobes in larvae. Through a well-orchestrated set of developmental events during metamorphosis, axon branches to both lobes degenerate prior to the formation of adult connections. Here, we analyze ultrastructural changes underlying axon pruning by using a genetically encoded electron microscopic (EM) marker to selectively label gamma neurons. By inhibiting axon pruning in combination with the use of this EM marker, we demonstrate a causal link between observed cellular events and axon pruning. These events include changes in axon ultrastructure, synaptic degeneration, and engulfment of degenerating axon fragments by glia for their subsequent breakdown via the endosomal-lysosomal pathway. Interestingly, glia selectively invade MB axon lobes at the onset of metamorphosis; this increase in cell number is independent of axon fragmentation. Our study reveals a key role for glia in the removal of axon fragments during developmental axon pruning.}, Author = {Watts, Ryan J. and Schuldiner, Oren and Perrino, John and Larsen, Camilla and Luo, Liqun}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0960-9822}, Journal = {Curr Biol}, Keywords = {Models, Biological;Mushroom Bodies;Neuroglia;Research Support, Non-U.S. Gov't;Nerve Degeneration;Comparative Study;Microscopy, Electron;Research Support, U.S. Gov't, P.H.S.;Drosophila;Lysosomes;Motor Neurons, Gamma;Fluorescent Antibody Technique;Metamorphosis, Biological;Endocytosis;Animals;24 Pubmed search results 2008;Axons}, Month = {4}, Nlm_Id = {9107782}, Number = {8}, Organization = {Department of Biological Sciences, Stanford University, Stanford, CA 94305 USA.}, Pages = {678-84}, Pii = {S0960982204002143}, Pubmed = {15084282}, Title = {Glia engulf degenerating axons during developmental axon pruning}, Uuid = {A226E904-0E69-487B-8954-7200DEC6B273}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cub.2004.03.035}} @article{Watts:1998, Abstract = {Networks of coupled dynamical systems have been used to model biological oscillators, Josephson junction arrays, excitable media, neural networks, spatial games, genetic control networks and many other self-organizing systems. Ordinarily, the connection topology is assumed to be either completely regular or completely random. But many biological, technological and social networks lie somewhere between these two extremes. Here we explore simple models of networks that can be tuned through this middle ground: regular networks 'rewired' to introduce increasing amounts of disorder. We find that these systems can be highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs. We call them 'small-world' networks, by analogy with the small-world phenomenon (popularly known as six degrees of separation. The neural network of the worm Caenorhabditis elegans, the power grid of the western United States, and the collaboration graph of film actors are shown to be small-world networks. Models of dynamical systems with small-world coupling display enhanced signal-propagation speed, computational power, and synchronizability. In particular, infectious diseases spread more easily in small-world networks than in regular lattices.}, Author = {Watts, D. J. and Strogatz, S. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Models, Biological;20 Networks;Communicable Diseases;Models, Neurological;research support, u.s. gov't, non-p.h.s.;Caenorhabditis elegans;Models, Theoretical;Nerve Net;Animals;Games, Experimental;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0410462}, Number = {6684}, Organization = {Department of Theoretical and Applied Mechanics, Cornell University, Ithaca, New York 14853, USA. djw24\@columbia.edu}, Pages = {440-2}, Pubmed = {9623998}, Title = {Collective dynamics of 'small-world' networks}, Uuid = {7BD0CDE4-D019-432B-AAF1-E0F5D8683D6C}, Volume = {393}, Year = {1998}, url = {papers/Watts_Nature1998.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/30918}} @article{Webster:1973, Abstract = {0002-9106 Journal Article}, Author = {Webster, W. and Shimada, M. and Langman, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Am J Anat}, Keywords = {Floxuridine/*pharmacology;Pregnancy;Cell Differentiation/*drug effects;Animals;Epithelial Cells;Cell Movement/drug effects;Female;Bromodeoxyuridine/*pharmacology;Kinetics;Maternal-Fetal Exchange;01 Adult neurogenesis general;DNA/biosynthesis;Neurons;A, T abstr;Mice;Cell Nucleus/drug effects;Benzocycloheptenes/*pharmacology;Mitosis/drug effects;Cerebral Cortex/drug effects/*embryology}, Number = {1}, Pages = {67-85}, Pubmed = {4267342}, Title = {Effect of fluorodeoxyuridine, colcemid, and bromodeoxyuridine on developing neocortex of the mouse}, Uuid = {1DDE40FF-65E0-46D3-9754-3A96DFE91322}, Volume = {137}, Year = {1973}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=4267342}} @article{Wefelmeyer:2007, Author = {Wefelmeyer, Winnie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, non-u.s. gov't;comment;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8102140}, Number = {40}, Organization = {Department of Pharmacology, University of Oxford, Oxford OX1 3QT, United Kingdom. winnie.wefelmeyer\@pharm.ox.ac.uk}, Pages = {10649-50}, Pii = {27/40/10649}, Pubmed = {17913898}, Title = {The influence of GABA on dendritic development in vivo}, Uuid = {4BEBA2ED-6DDD-4D0B-B6B8-DEA5BB39D62D}, Volume = {27}, Year = {2007}, url = {papers/Wefelmeyer_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3111-07.2007}} @article{Wegiel:1998, Abstract = {The numerical density of microglial cells is reduced by 47\%in the corpus callosum, by 37\%in the parietal cortex and by 34\%in the frontal cortex of mice mutant at the op locus which are totally devoid of colony stimulating factor-1 (CSF-1), the major growth factor for macrophages. Moreover, microglia in the frontal cortex of the op/op mice are smaller and have shorter cytoplasmic processes compared to control mice. Study suggests that CSF-1 plays a role in vivo in the formation and maturation of microglia and has little or no effect on perivascular cells.}, Author = {Wegiel, J. and Wi\'{s}niewski, H. M. and Dziewiatkowski, J. and Tarnawski, M. and Kozielski, R. and Trenkner, E. and Wiktor-Jedrzejczak, W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Brain;Macrophage Colony-Stimulating Factor;Mutation;Mice;Osteopetrosis;Frontal Lobe;Immunohistochemistry;Cell Count;11 Glia;Microglia;Parietal Lobe;Support, Non-U.S. Gov't;Male;Animals;Mice, Inbred Strains;Corpus Callosum}, Medline = {98398418}, Month = {8}, Nlm_Id = {0045503}, Number = {1}, Organization = {New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, New York, NY 10314, USA.}, Pages = {135-9}, Pii = {S0006899398006180}, Pubmed = {9729335}, Title = {Reduced number and altered morphology of microglial cells in colony stimulating factor-1-deficient osteopetrotic op/op mice}, Uuid = {D3F404B1-3EFF-4A75-B1EB-49258DF6387A}, Volume = {804}, Year = {1998}} @article{Wehner:2003, Abstract = {Differentiation of bone marrow (BM) cells into astroglia expressing the glial fibrillary acidic protein (GFAP) has been reported in vitro and after intracerebral or systemic BM transplantation. In contrast, recent data suggest that astrocytic differentiation does not occur from BM-derived cells in vivo. Using transgenic mice that express the enhanced green fluorescent protein (GFP) under the control of the human glial fibrillary acidic protein (GFAP) promoter, we investigated the potential of adult murine BM-derived cells to differentiate into macroglia. In the brains of GFAP-GFP transgenic mice, astrocytes were brightly fluorescent from the expression of GFP. When BM from these animals was transplanted into lethally irradiated wild-type animals, the transgene was detected in the reconstituted hematopoietic system, but no GFP expression was found in the nervous system. In contrast, GFAP-GFP neuroectodermal anlage grafted into adult wild-type striatum gave rise to GFP-expressing astrocytes. Because cerebral ischemia has been suggested to promote the differentiation of BM-derived cells into astrocytes, BM chimeric mice were subjected to focal cerebral ischemia. No GFP-positive cells were found in the ischemic or contralateral hemispheres of these brains. Even after direct injection of GFAP-GFP transgenic BM cells into wild-type striatum, no GFP-expressing astroglia were detected. To test the hypothesis that the in vitro environment might be more permissible for astroglial differentiation, we cultured BM from mice that constitutively express GFP, BM cells expressing GFP from a retroviral vector, and BM from GFAP-GFP transgenic mice on astrocytes and on organotypic hippocampal slices. In all experimental paradigms, BM-derived cells were found to differentiate into ramified microglia but not into GFAP-expressing astrocytes.}, Author = {Wehner, Tim and B{\"o}ntert, Matthias and Ey{\"u}poglu, Ilker and Prass, Konstantin and Prinz, Marco and Klett, Francisco Fern{\'a}ndez and Heinze, Matthias and Bechmann, Ingo and Nitsch, Robert and Kirchhoff, Frank and Kettenmann, Helmut and Dirnagl, Ulrich and Priller, Josef}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Glial Fibrillary Acidic Protein;Cell Differentiation;Animals;Astrocytes;In Vitro;Coculture Techniques;Brain Tissue Transplantation;Cells, Cultured;Humans;Stem Cell Transplantation;Brain;Microglia;Mice, Transgenic;Hippocampus;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Radiation Chimera;Bone Marrow Cells;Promoter Regions (Genetics);Mice;Ischemic Attack, Transient;Graft Survival;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22716523}, Month = {6}, Nlm_Id = {8102140}, Number = {12}, Organization = {Department of Neurology, Charit{\'e}, Humboldt-University, 10117 Berlin, Germany.}, Pages = {5004-11}, Pii = {23/12/5004}, Pubmed = {12832523}, Title = {Bone marrow-derived cells expressing green fluorescent protein under the control of the glial fibrillary acidic protein promoter do not differentiate into astrocytes in vitro and in vivo}, Uuid = {F2F9AA7C-800D-460C-86AF-AFAFE2F04DF6}, Volume = {23}, Year = {2003}, url = {papers/Wehner_JNeurosci2003.pdf}} @article{Weimann:2003, Abstract = {Heterokaryons are the product of cell fusion without subsequent nuclear or chromosome loss. Decades of research using Sendai-virus or polyethylene glycol (PEG)-mediated fusion in tissue culture showed that the terminally differentiated state of a cell could be altered. But whether stable non-dividing heterokaryons could occur in animals has remained unclear. Here, we show that green fluorescent protein (GFP)-positive bone-marrow-derived cells (BMDCs) contribute to adult mouse Purkinje neurons through cell fusion. The formation of heterokaryons increases in a linear manner over 1.5 years and seems to be stable. The dominant Purkinje neurons caused the BMDC nuclei within the resulting heterokaryons to enlarge, exhibit dispersed chromatin and activate a Purkinje neuron-specific transgene, L7-GFP. The observed reprogrammed heterokaryons that form in brain may provide insights into gene regulation associated with cell-fate plasticity.}, Author = {Weimann, James M. and Johansson, Clas B. and Trejo, Angelica and Blau, Helen M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1465-7392}, Journal = {Nat Cell Biol}, Keywords = {Research Support, Non-U.S. Gov't;In Situ Hybridization, Fluorescence;Purkinje Cells;Animals;Chromatin;Bone Marrow Transplantation;Cell Fusion;Mice, Transgenic;Mice, Inbred C57BL;Green Fluorescent Proteins;08 Aberrant cell cycle;17 Transplant Regeneration;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Flow Cytometry;Mice;22 Stem cells;24 Pubmed search results 2008;Luminescent Proteins;Transgenes}, Medline = {22954634}, Month = {11}, Nlm_Id = {100890575}, Number = {11}, Organization = {Baxter Laboratory in Genetic Pharmacology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. jweimann\@stanford.edu}, Pages = {959-66}, Pii = {ncb1053}, Pubmed = {14562057}, Title = {Stable reprogrammed heterokaryons form spontaneously in Purkinje neurons after bone marrow transplant}, Uuid = {52FC753E-E9C3-11DA-920C-000D9346EC2A}, Volume = {5}, Year = {2003}, url = {papers/Weimann_NatCellBiol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/ncb1053}} @article{Weimann:2003a, Abstract = {We show here that cells within human adult bone marrow can contribute to cells in the adult human brain. Cerebellar tissues from female patients with hematologic malignancies, who had received chemotherapy, radiation, and a bone marrow transplant, were analyzed. Brain samples were obtained at autopsy from female patients who received male (sex-mismatched) or female (sex-matched, control) bone marrow transplants. Cerebella were evaluated in 10-microm-thick, formaldehyde-fixed, paraffin-embedded sections that encompassed up to approximately 50\%of a human Purkinje nucleus. A total of 5,860 Purkinje cells from sex-mismatched females and 3,202 Purkinje cells from sex-matched females were screened for Y chromosomes by epifluorescence. Confocal laser scanning microscopy allowed definitive identification of the sex chromosomes within the morphologically distinct Purkinje cells. In the brains of females who received male bone marrow, four Purkinje neurons were found that contained an X and a Y chromosome and two other Purkinje neurons contained more than a diploid number of sex chromosomes. No Y chromosomes were detected in the brains of sex-matched controls. The total frequency of male bone marrow contribution to female Purkinje cells approximated 0.1\%. This study demonstrates that although during human development Purkinje neurons are no longer generated after birth, cells within the bone marrow can contribute to these CNS neurons even in adulthood. The underlying mechanism may be caused either by generation de novo of Purkinje neurons from bone marrow-derived cells or by fusion of marrow-derived cells with existing recipient Purkinje neurons.}, Author = {Weimann, James M. and Charlton, Carol A. and Brazelton, Timothy R. and Hackman, Robert C. and Blau, Helen M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {In Situ Hybridization;Chromosomes, Human, Y;Purkinje Cells;Research Support, Non-U.S. Gov't;Adult;17 Transplant Regeneration;Cell Fusion;Female;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;Bone Marrow Transplantation;22 Stem cells;Humans;Brain;24 Pubmed search results 2008;Neurons}, Medline = {22480347}, Month = {2}, Nlm_Id = {7505876}, Number = {4}, Organization = {Baxter Laboratory for Genetic Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.}, Pages = {2088-93}, Pii = {0337659100}, Pubmed = {12576546}, Title = {Contribution of transplanted bone marrow cells to Purkinje neurons in human adult brains}, Uuid = {52FC79D0-E9C3-11DA-920C-000D9346EC2A}, Volume = {100}, Year = {2003}, url = {papers/Weimann_ProcNatlAcadSciUSA2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0337659100}} @article{Weimer:2006, Abstract = {Dynamic regulation of neuronal cytoskeletal machinery in response to extracellular cues enables distinct changes in neuronal development in the cerebral cortex. In this issue of Neuron, three related studies on doublecortin-like kinase, a microtubule-associated protein related to doublecortin, by Shu et al., Koizumi et al., and Deuel et al., provide evidence that doublecortin-like kinase is essential for proper neurogenesis, neuronal migration, and axonal wiring.}, Author = {Weimer, Jill M. and Anton, E. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Aging;Embryonic Development;Embryo;10 Development;24 Pubmed search results 2008;Embryo, Nonmammalian;Neuropeptides;Drug Synergism;Protein-Serine-Threonine Kinases;Animals, Newborn;comment;Animals;Microtubule-Associated Proteins;Cerebral Cortex;review;Embryo, Mammalian}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Neuroscience Center, Department of Cell and Molecular Physiology, The University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.}, Pages = {3-4}, Pii = {S0896-6273(05)01104-9}, Pubmed = {16387632}, Title = {Doubling up on microtubule stabilizers: synergistic functions of doublecortin-like kinase and doublecortin in the developing cerebral cortex}, Uuid = {105DC4E6-8E15-41CD-8565-E4D900FB3206}, Volume = {49}, Year = {2006}, url = {papers/Weimer_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.12.016}} @article{Weinberg:1980, Author = {Weinberg, R. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {15 ERVs retroelements;24 Pubmed search results 2008;Species Specificity;Virus Replication;Retroviridae;DNA, Viral;15 Retrovirus mechanism;Animals;Chickens;Cell Transformation, Viral;Mice;Recombination, Genetic}, Month = {12}, Nlm_Id = {0413066}, Number = {3}, Pages = {643-4}, Pii = {0092-8674(80)90537-1}, Pubmed = {7460007}, Title = {Origins and roles of endogenous retroviruses}, Uuid = {3CDEDFDA-6B1D-4B89-84E1-DAA420324201}, Volume = {22}, Year = {1980}, url = {papers/Weinberg_Cell1980.pdf}} @article{Weinberg:1991, Abstract = {Human immunodeficiency virus type 1 (HIV-1) infection of T lymphocytes requires cellular proliferation and DNA synthesis. Human monocytes were shown to have low DNA synthesis rates, yet the monocytotropic BaL isolate of HIV-1 was able to infect these cells efficiently. Monocytes that were irradiated to assure no DNA synthesis could also be readily infected with HIV-1BaL. Such infections were associated with the integration of HIV-1BaL DNA into the high molecular weight, chromosomal DNA of monocytes. Thus, normal, nonproliferating monocytes differ from T lymphocytes in that a productive HIV-1 infection can occur independently of cellular DNA synthesis. These results suggest that normal nonproliferating mononuclear phagocytes, which are relatively resistant to the destructive effects of this virus, may serve as persistent and productive reservoirs for HIV-1 in vivo.}, Author = {Weinberg, J. B. and Matthews, T. J. and Cullen, B. R. and Malim, M. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0022-1007}, Journal = {J Exp Med}, Keywords = {Monocytes;Macrophage Colony-Stimulating Factor;HIV Core Protein p24;RNA-Directed DNA Polymerase;Research Support, Non-U.S. Gov't;HIV-1;HIV-1 Reverse Transcriptase;Research Support, U.S. Gov't, P.H.S.;Granulocyte-Macrophage Colony-Stimulating Factor;DNA;DNA, Viral;11 Glia;Research Support, U.S. Gov't, Non-P.H.S.;Cells, Cultured;Humans;Proteins}, Medline = {92078858}, Month = {12}, Nlm_Id = {2985109R}, Number = {6}, Organization = {Department of Medicine, Veterans Affairs, Medical Center, Durham, North Carolina.}, Pages = {1477-82}, Pubmed = {1720811}, Title = {Productive human immunodeficiency virus type 1 (HIV-1) infection of nonproliferating human monocytes}, Uuid = {25CDFB48-B3DB-477C-98C9-C92E93B4F3CF}, Volume = {174}, Year = {1991}} @article{Weinstein:1972, Author = {Weinstein, I. B. and Gebert, R. and Stadler, U. C. and Orenstein, J. M. and Axel, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Bromodeoxyuridine;Liver Neoplasms;RNA, Viral;Animals;RNA Viruses;Cells, Cultured;Leukosis Virus, Avian;Rats;Dimethyl Sulfoxide;Deoxyribonucleotides;15 Retrovirus mechanism;Uridine;Retroviridae;DNA Nucleotidyltransferases;Carcinoma, Hepatocellular;Fluorenes;24 Pubmed search results 2008;Tritium;Neoplasms, Experimental;15 ERVs retroelements;Microscopy, Electron;Oncogenic Viruses}, Medline = {73042831}, Month = {12}, Nlm_Id = {0404511}, Number = {65}, Pages = {1098-100}, Pubmed = {4343844}, Title = {Type C virus from cell cultures of chemically induced rat hepatomas}, Uuid = {8DFFB51B-4328-11DB-A5D2-000D9346EC2A}, Volume = {178}, Year = {1972}} @article{Weiss:2003a, Abstract = {Immune rejection of transplanted material is a potential complication of organ donation. In response to tissue transplantation, immune rejection has two components: a host defense directed against the grafted tissue and an immune response from the grafted tissue against the host (graft vs host disease). To treat immune rejection, transplant recipients are typically put on immunosuppression therapy. Complications may arise from immune suppression or from secondary effects of immunosuppression drugs. Our preliminary work indicated that stem cells may be xenotransplanted without immunosuppression therapy. Here, we investigated the survival of pig stem cells derived from umbilical cord mucous connective tissue (UCM) after transplantation into rats. Our data demonstrate that UCM cells survive at least 6 weeks without immune suppression of the host animals after transplantation into either the brain or the periphery. In the first experiment, UCM cells were transplanted into the rat brain and recovered in that tissue 2-6 weeks posttransplantation. At 4 weeks posttransplantation, the UCM cells engrafted into the brain along the injection tract. The cells were small and roughly spherical. The transplanted cells were positively immunostained using a pig-specific antibody for neuronal filament 70 (NF70). In contrast, 6 weeks posttransplantation, about 10\%of the UCM cells that were recovered had migrated away from the injection site into the region just ventral to the corpus callosum; these cells also stained positively for NF70. In our second experiment, UCM cells that were engineered to constitutively express enhanced green fluorescent protein (eGFP) were transplanted. These cells were recovered 2-4 weeks after brain transplantation. Engrafted cells expressing eGFP and positively staining for NF70 were recovered. This finding indicates a potential for gene therapy. In the third experiment, to determine whether depositing the graft into the brain protected UCM cells from immune detection/clearance, UCM cells were injected into the tail vein and/or the semitendinosis muscle in a group of animals. UCM cells were recovered from the muscle or within the kidney 3 weeks posttransplantation. In control experiments, rat brains were injected with PKH 26-labeled UCM cells that had been lysed by repeated sonic disruption. One and 2 weeks following injection, no PKH 26-labeled neurons or glia were observed. Taken together, these data indicate that UCM cells can survive xenotransplantation and that a subset of the UCM cells respond to local signals to differentiate along a neural lineage.}, Author = {Weiss, M. L. and Mitchell, K. E. and Hix, J. E. and Medicetty, S. and El-Zarkouny, S. Z. and Grieger, D. and Troyer, D. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0014-4886}, Journal = {Exp Neurol}, Keywords = {Cell Survival;Fluorescent Dyes;Rats, Inbred Lew;Animals;Stem Cell Transplantation;Cells, Cultured;Rats;Transfection;Umbilical Cord;Brain;Swine;Rats, Sprague-Dawley;Neurosurgical Procedures;Neurofilament Proteins;11 Glia;Green Fluorescent Proteins;Organic Chemicals;Research Support, U.S. Gov't, P.H.S.;Mesoderm;Immunohistochemistry;Stem Cells;Graft Survival;Injections;Luminescent Proteins;Research Support, Non-U.S. Gov't}, Medline = {22777794}, Month = {8}, Nlm_Id = {0370712}, Number = {2}, Organization = {Department of Anatomy and Physiology, Kansas State University, College of Veterinary Medicine, Manhattan, KS 66506-5602, USA. weiss\@vet.ksu.edu}, Pages = {288-99}, Pii = {S0014488603001286}, Pubmed = {12895440}, Title = {Transplantation of porcine umbilical cord matrix cells into the rat brain}, Uuid = {87B7FBD5-BC09-4081-93A9-4D0EC90D2528}, Volume = {182}, Year = {2003}} @article{Weiss:2002, Abstract = {Viruses use specific cell surface receptors to bind to and subsequently gain entry into their host cells. Some retroviruses such as HIV-1 and HIV-2 utilize one receptor for high-affinity binding (CD4), and a separate coreceptor to mediate fusion of the viral envelope with the cell membrane (CCR5 or CXCR4). The identification of these receptors explains the cellular tropism of HIV, and hence its pathogenesis leading to immune deficiency (T-helper cell depletion), the wasting syndrome (macrophage infection), and dementia (microglia infection). HIV can infect cells by membrane fusion at the cell surface and by receptor-mediated endocytosis. Knowledge of the HIV receptors has led to practical developments such as inhibitory drugs, reasons for genetic resistance to infection, and should inform the judicious choice of candidate vaccines.}, Author = {Weiss, Robin A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1521-6543}, Journal = {IUBMB Life}, Keywords = {Receptors, CXCR4;Animals;HIV-1;Humans;Protein Binding;review, tutorial;review;Acquired Immunodeficiency Syndrome;Models, Biological;Cell Membrane;Antigens, CD4;11 Glia;Epitopes;Receptors, CCR5;DNA, Complementary;Mice;Microscopy, Electron;HIV-2;HIV Envelope Protein gp120;Research Support, Non-U.S. Gov't}, Medline = {22115640}, Nlm_Id = {100888706}, Number = {4-5}, Organization = {Department of Immunology and Molecular Pathology, University College London, United Kingdom. r.weiss\@ucl.ac.uk}, Pages = {201-5}, Pubmed = {12120995}, Title = {HIV receptors and cellular tropism}, Uuid = {0E629AAA-0747-453F-A924-AAE6A6187973}, Volume = {53}, Year = {2002}} @article{Weiss:2003, Abstract = {We studied the postnatal development of the radial glial scaffold in the dentate gyrus of reeler mice, lacking the extracellular matrix protein Reelin, in scrambler mice, deficient in the intracellular adaptor protein disabled1 (Dab1), which is required for the transmission of the Reelin signal into the cell, and in mutant mice lacking the Reelin receptors apolipoprotein receptor 2 (ApoER2) and/or the very low density lipoprotein receptor (VLDLR), known to transmit the Reelin signal via Dab1. By immunolabeling for the glial fibrillary acidic protein (GFAP), we show that a regular dentate radial glial scaffold fails to form in mutants deficient of Reelin, Dab1, and VLDLR and ApoER2. Mutant mice lacking only one of the Reelin receptors, VLDLR or ApoER2, display a gradual expression of the radial glial defects seen in mutants that lack both receptors. Our results suggest that Reelin signaling via ApoER2, VLDLR, and Dab1 is required for the formation of a regular radial glial scaffold in the dentate gyrus.}, Author = {Weiss, Karl Heinz and Johanssen, Celine and Tielsch, Albrecht and Herz, Joachim and Deller, Thomas and Frotscher, Michael and F{\"o}rster, Eckart}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Male;Mice;10 Development;Mice, Knockout;Research Support, Non-U.S. Gov't;Neuroglia;Receptors, Lipoprotein;10 Hippocampus;Comparative Study;Female;Dentate Gyrus;Animals;Cell Movement;Nervous System Malformations;Receptors, LDL;Mice, Neurologic Mutants}, Medline = {22573054}, Month = {5}, Nlm_Id = {0406041}, Number = {1}, Organization = {Anatomisches Institut, Universit{\"a}t Freiburg, D-79104 Freiburg, Germany.}, Pages = {56-65}, Pubmed = {12687696}, Title = {Malformation of the radial glial scaffold in the dentate gyrus of reeler mice, scrambler mice, and ApoER2/VLDLR-deficient mice}, Uuid = {87E33153-CFF4-4447-A081-C523F00D71B9}, Volume = {460}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10644}} @article{Weiss:1986, Abstract = {Striatal neurons were cultured from the fetal mouse brain and maintained in serum-free medium for 14-21 days in vitro (DIV). Pretreatment of the culture dishes successively with a polycation followed by fetal calf serum resulted in rapid neuron attachment and neurite proliferation. After 9-10 DIV, electron microscope observations revealed the presence of vesicles in axon terminals forming mature synapses with axons and perikarya of adjacent neurons and in varicosities along extended axons. Synapsin I, a synaptic vesicle-specific protein, was present only in neuronal perikarya after 3 DIV, in perikarya and in varicosities along extended axons after 6 DIV, and in varicosities and contact points between axon terminals and adjacent axons or perikarya after 11-14 DIV. Neurotransmitter-stimulated intracellular formation of cAMP decreased markedly during neuronal differentiation. Inositol phosphate formation in response to neurotransmitters, however, increased significantly throughout the period of striatal neuronal development. K+ (56 mM) depolarization resulted in a 2-fold increase in endogenous gamma-aminobutyric acid (GABA) release from striatal neurons, 50\%of which was Ca2+-dependent, between 3 and 11 DIV. Between 11 and 14 DIV, subsequent to synapse formation (as revealed by electron microscope observations), GABA release evoked by 56 mM K+ increased up to 5-fold, 75\%of which was Ca2+-dependent. It appears that the complete differentiation of striatal neurons in serum-free medium may provide a suitable model for the study of the physiological and regulatory mechanisms involved in nerve cell development. 0027-8424 Journal Article}, Author = {Weiss, S. and Pin, J. P. and Sebben, M. and Kemp, D. E. and Sladeczek, F. and Gabrion, J. and Bockaert, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Nerve Tissue Proteins/metabolism;Cell Differentiation;T both;Inositol Phosphates/metabolism;Corpus Striatum/*cytology/embryology;Vasoactive Intestinal Peptide/pharmacology;Microscopy, Electron, Scanning;Synapses/*ultrastructure;Time Factors;Cyclic AMP/metabolism;Synapsins;gamma-Aminobutyric Acid/metabolism;Mice;Animals;Cells, Cultured;23 Technique;Support, Non-U.S. Gov't}, Number = {7}, Pages = {2238-42}, Title = {Synaptogenesis of cultured striatal neurons in serum-free medium: a morphological and biochemical study}, Uuid = {E6E66F3D-ACB5-42C1-8D94-C20DABACA2CA}, Volume = {83}, Year = {1986}, url = {papers/Weiss_ProcNatlAcadSciUSA1986.pdf}} @article{Weisskopf:1991, Abstract = {Combined retrograde transport of Rhodamine-labeled latex beads and intracellular injection of Lucifer Yellow in aldehyde-fixed slices of areas 17 and 18 in kittens indicate that neurons with similar dendritic morphology send axons into the corpus callosum from the 17/18 border and from parts of area 17 destined to become acallosal. At both sites callosally projecting neurons (callosal neurons) include pyramids, spiny stellate cells and star-pyramids; two types of pyramidal neurons can be distinguished on the basis of the complexity of their apical dendrites. At both sites, the dendritic morphology of callosal neurons appears basically unaffected by the ablation at the beginning of the second postnatal week of the contralateral areas 17 and 18 to which they have sent their axon. Thus the dendritic morphology of this type of cortical neuron seems independent of retrograde signals coming from their contralateral target and may instead depend on "programs" intrinsic to the neurons and/or conditions acting locally on their cell bodies, dendrites or initial axon collaterals.}, Author = {Weisskopf, M. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0014-4819}, Journal = {Exp Brain Res}, Keywords = {Rhodamines;Animals;Phenotype;Axons;Not relevant;11 Glia;Dendrites;Axonal Transport;Animals, Newborn;Support, Non-U.S. Gov't;Cerebral Cortex;Neurons;Isoquinolines;Horseradish Peroxidase;Tissue Fixation;Visual Cortex;Corpus Callosum;Cats}, Medline = {92097633}, Nlm_Id = {0043312}, Number = {1}, Organization = {Institut d'Anatomie, Lausanne, Switzerland.}, Pages = {151-8}, Pubmed = {1721871}, Title = {Neurons with callosal projections in visual areas of newborn kittens: an analysis of their dendritic phenotype with respect to the fate of the callosal axon and of its target}, Uuid = {30C30C7B-5FE4-4C8B-98B6-373368926993}, Volume = {86}, Year = {1991}} @article{Weissman:2003, Abstract = {Radial glial cells play at least two crucial roles in cortical development: neuronal production in the ventricular zone (VZ) and the subsequent guidance of neuronal migration. There is evidence that radial glia-like cells are present not only during development but in the adult mammalian brain as well. In addition, radial glial cells appear to be neurogenic in the central nervous system of a number of vertebrate species. We demonstrate here that most dividing progenitor cells in the embryonic human VZ express radial glial proteins. Furthermore, we provide evidence that radial glial cells maintain a vimentin-positive radial fiber throughout each stage of cell division. Asymmetric inheritance of this fiber may be an important factor in determining how neuronal progeny will migrate into the developing cortical plate. Although radial glial cells have traditionally been characterized by their role in guiding migration, their role as neuronal progenitors may represent their defining characteristic throughout the vertebrate CNS. 22648192 1047-3211 Journal Article}, Author = {Weissman, T. and Noctor, S. C. and Clinton, B. K. and Honig, L. S. and Kriegstein, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Cereb Cortex}, Keywords = {Rodentia;Human;10 Development;Rats;Neurons/cytology/*physiology;Stem Cells/physiology;Mitosis/physiology;Animal;Cerebral Cortex/cytology/embryology/growth &development/physiology;Neuroglia/classification/*cytology/*physiology;Support, Non-U.S. Gov't;Vimentin/metabolism;Cerebral Ventricles/cytology/embryology/*growth &development/physiology;Cell Lineage/physiology;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Cell Differentiation/physiology;Reptiles;Adaptation, Physiological/*physiology;Signal Transduction/physiology;F}, Number = {6}, Organization = {Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, 630 W. 168th Street, New York, NY 10032, USA.}, Pages = {550-9}, Pubmed = {12764028}, Title = {Neurogenic radial glial cells in reptile, rodent and human: from mitosis to migration}, Uuid = {16087AFF-8FC4-421C-BD5F-E3FFB564C317}, Volume = {13}, Year = {2003}, url = {papers/Weissman_CerebCortex2003.pdf}} @article{Weissman:2004, Abstract = {The majority of neurons in the adult neocortex are produced embryonically during a brief but intense period of neuronal proliferation. The radial glial cell, a transient embryonic cell type known for its crucial role in neuronal migration, has recently been shown to function as a neuronal progenitor cell and appears to produce most cortical pyramidal neurons. Radial glial cell modulation could thus affect neuron production, neuronal migration, and overall cortical architecture; however, signaling mechanisms among radial glia have not been studied directly. We demonstrate here that calcium waves propagate through radial glial cells in the proliferative cortical ventricular zone (VZ). Radial glial calcium waves occur spontaneously and require connexin hemichannels, P2Y1 ATP receptors, and intracellular IP3-mediated calcium release. Furthermore, we show that wave disruption decreases VZ proliferation during the peak of embryonic neurogenesis. Taken together, these results demonstrate a radial glial signaling mechanism that may regulate cortical neuronal production.}, Author = {Weissman, Tamily A. and Riquelme, Patricio A. and Ivic, Lidija and Flint, Alexander C. and Kriegstein, Arnold R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-22 16:00:02 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {10 Development;Calcium Signaling;Animals;Rats;Neocortex;Cell Communication;Rats, Sprague-Dawley;Receptors, Cytoplasmic and Nuclear;Cell Movement;Calcium;Connexins;Research Support, U.S. Gov't, P.H.S.;Neuroglia;Neurons;Calcium Channels;Cell Division;Stem Cells;Receptors, Purinergic P2;Research Support, Non-U.S. Gov't; Spontaneous activity; calcium imaging; neurogenesis; 21 Activity-development; Structure-Activity Relationship; visual cortex; ideas; Grants}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {Center for Neurobiology and Behavior, Columbia University, New York, NY 10032, USA.}, Pages = {647-61}, Pii = {S0896627304004970}, Pubmed = {15339647}, Title = {Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex}, Uuid = {5906C5F8-FEC2-46D5-A30D-14BC3558B601}, Volume = {43}, Year = {2004}, url = {papers/Weissman_Neuron2004.pdf}, Bdsk-File-2 = {papers/Weissman_Neuron2004a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.08.015}} @article{Weller:1993, Abstract = {The effects of DNA substitution by the thymidine analogue 5-bromodeoxyuridine (BrdU) on cell cycle progression and micronucleus induction were studied in different mammalian cell cultures. Simultaneous flow cytometric measurements of DNA content and side scatter of nuclei in Chinese hamster embryo (CHE) cells revealed a concentration-dependent temporary block in the G2/M phase of the first cell cycle. NIH 3T3 cells and human amniotic fluid fibroblast-like cells, on the contrary, did not show any cell cycle disturbances in the presence of BrdU. Micronucleus frequency increased as soon as CHE cells started to divide and reached a plateau when all cells have divided. The height of this plateau was almost equal for 60 and 100 microM BrdU. This saturation of micronucleus induction was due to a saturation of BrdU incorporation into DNA already at a doses of 60 microM as shown by the BrdU/Hoechst quenching technique. Indirect immunofluorescent staining of kinetochores with CREST antibodies revealed that nearly all BrdU-induced micronuclei were kinetochore-negative suggesting the presence of acentric chromosome fragments in these micronuclei. DNA distributions of micronuclei measured by flow cytometry showed several peaks representing micronuclei which contain DNA fragments of defined sizes induced by non-random breakage of chromosomes 1 and X as verified by flow karyotyping and C-banding.}, Author = {Weller, E. M. and Dietrich, I. and Viaggi, S. and Beisker, W. and N{\"u}sse, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0267-8357}, Journal = {Mutagenesis}, Keywords = {Hamsters;Dose-Response Relationship, Drug;Animals;Humans;Cells, Cultured;Cell Cycle;DNA;Fibroblasts;Mutagens;Micronuclei, Chromosome-Defective;Chromosome Aberrations;15 Retrovirus mechanism;23 Technique;Cricetulus;01 Adult neurogenesis general;3T3 Cells;Karyotyping;Flow Cytometry;Mice;24 Pubmed search results 2008;Bromodeoxyuridine}, Medline = {94049138}, Month = {9}, Nlm_Id = {8707812}, Number = {5}, Organization = {GSF-Institut f{\"u}r Biophysikalische Strahlenforschung, Arbeitsgruppe Durchflusszytometrie, Neuherberg, FRG.}, Pages = {437-44}, Pubmed = {8231825}, Title = {Flow cytometric analysis of bromodeoxyuridine-induced micronuclei}, Uuid = {FFF7B16C-013C-49C9-B5C7-2E4210F87DAC}, Volume = {8}, Year = {1993}} @article{Wellman:2001, Abstract = {Chronic stress produces deficits in cognition accompanied by alterations in neural chemistry and morphology. For example, both stress and chronic administration of corticosterone produce dendritic atrophy in hippocampal neurons (Woolley C, Gould E, McEwen BS. 1990. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 531:225-231; Watanabe Y, Gould E, McEwen BS, 1992b. Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588:341-345). Prefrontal cortex is also a target for glucocorticoids involved in the stress response (Meaney MJ, Aitken DH. 1985. [(3)H]Dexamethasone binding in rat frontal cortex. Brain Res 328:176-180); it shows neurochemical changes in response to stress (e.g., Luine VN, Spencer RL, McEwen BS. 1993. Effect of chronic corticosterone ingestion on spatial memory performance and hippocampal serotonergic function. Brain Res 616:55-70; Crayton JW, Joshi I, Gulati A, Arora RC, Wolf WA. 1996. Effect of corticosterone on serotonin and catecholamine receptors and uptake sites in rat frontal cortex. Brain Res 728:260-262; Takao K, Nagatani T, Kitamura Y, Yamawaki S. 1997. Effects of corticosterone on 5-HT(1A) and 5-HT(2) receptor binding and on the receptor-mediated behavioral responses of rats. Eur J Pharmacol 333:123-128; Sandi C, Loscertales M. 1999. Opposite effects on NCAM expression in the rat frontal cortex induced by acute vs. chronic corticosterone treatments. Brain Res 828:127-134), and mediates many of the behaviors that are altered by chronic corticosterone administration (e.g., Lyons DM, Lopez JM, Yang C, Schatzberg AF. 2000. Stress-level cortisol treatment impairs inhibitory control of behavior in monkeys. J Neurosci 20:7816-7821). To determine if glucocorticoid-induced morphological changes also occur in medial prefrontal cortex, the effects of chronic corticosterone administration on dendritic morphology in this corticolimbic structure were assessed. Adult male rats received s.c. injections of either corticosterone (10 mg in 250 microL sesame oil; n = 8) or vehicle (250 microL; n = 8) daily for 3 weeks. A third group of rats served as intact controls (n = 4). Brains were stained using a Golgi-Cox procedure and pyramidal neurons in layer II-III of medial prefrontal cortex were drawn; dendritic morphology was quantified in three dimensions. Sholl analyses demonstrated a significant redistribution of apical dendrites in corticosterone-treated animals: the amount of dendritic material proximal to the soma was increased relative to intact rats, while distal dendritic material was decreased relative to intact animals. Thus, chronic glucocorticoid administration dramatically reorganized apical arbors in medial prefrontal cortex. This reorganization likely reflects functional changes and may contribute to stress-induced changes in cognition.}, Author = {Wellman, C. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Research Support, Non-U.S. Gov't;Dendrites;Rats, Sprague-Dawley;Rats;Pyramidal Cells;Prefrontal Cortex;Corticosterone;Stress;Cell Count;Male;Animals;24 Pubmed search results 2008}, Medline = {21611752}, Month = {11}, Nlm_Id = {0213640}, Number = {3}, Organization = {Department of Psychology and Program in Neural Science, Indiana University, 1101 E. 10th Street, Bloomington, IN 47405, USA. wellmanc\@indiana.edu}, Pages = {245-53}, Pii = {10.1002/neu.1079}, Pubmed = {11745662}, Title = {Dendritic reorganization in pyramidal neurons in medial prefrontal cortex after chronic corticosterone administration}, Uuid = {07CEEB33-DCF5-48E4-A7ED-878A16B6D90D}, Volume = {49}, Year = {2001}} @article{Wen:2002, Abstract = {The functions of the presenilin-1 (PS-1) protein remain largely unknown. In adult brain PS-1 is expressed principally in neurons. However during development PS-1 is expressed more widely including in embryonic neural progenitors. To determine if PS-1 is expressed in neural progenitors in adult hippocampus we used bromodeoxyuridine (BrdU) labeling combined with immunostaining for BrdU, PS-1 and markers of neuronal or glial differentiation. Most BrdU labeled cells also expressed PS-1 at a time when few BrdU labeled cells expressed the early neuronal markers beta-III tubulin or TOAD-64 and none expressed mature neuronal (NeuN or calbindin) or astrocytic (GFAP) markers. Cells expressing PS-1 and the neural progenitor marker nestin were also found. Thus PS-1 is expressed in neural progenitor cells in adult hippocampus implying its possible role in neurogenesis in adult brain.}, Author = {Wen, P. H. and Friedrich, V. L. and Shioi, J. and Robakis, N. K. and Elder, G. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neurosci Lett}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {2}, Organization = {Department of Psychiatry, P.O. Box 1229, Mount Sinai School of Medicine, One Gustave Levy Place, 10029, New York, NY, USA}, Pages = {53-6.}, Title = {Presenilin-1 is expressed in neural progenitor cells in the hippocampus of adult mice}, Uuid = {35B9AA18-E7DA-4A30-813D-105812FBAFD9}, Volume = {318}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11796184}} @article{Wennberg:2003, Abstract = {OBJECTIVE: To examine interictal epileptiform and sleep potentials recorded intracranially from deep brain stimulation (DBS) electrodes in patients treated with DBS for epilepsy. Specifically, this study sought to determine whether the DBS-recorded potentials represent: (a) volume conduction from surface neocortical discharges or (b) transsynaptic propagation along cortical-subcortical pathways with local generation of the subcortical potentials near the DBS targets. METHODS: Six patients with intractable epilepsy treated with thalamic DBS of the central median nucleus (CM; one patient) or anterior thalamus (5 patients) who had focal interictal spikes were studied. Sleep potentials were also studied in a 7th patient with Parkinson disease treated with DBS of the subthalamic nucleus (STN). RESULTS: Focal interictal cortical spikes recorded by scalp electroencephalography (EEG) were recorded synchronously, but with opposite polarity, from the DBS electrodes in CM as well as the more superficial anterior thalamic contacts situated in the anterior nucleus (AN) and dorsal medial nucleus (DM). In referential montages, the subcortical potentials were of highest amplitude ipsilateral to the focal cortical spikes, with a small but reproducible amplitude decrement present at each electrode contact more distant from the cortical source, irrespective of the specific DBS target. Subcortical sleep potentials (K-complexes and sleep spindles) were also recorded synchronously and with inverse polarity compared to the corresponding scalp potentials, and appeared in a similar fashion at all subcortical sites sampled by the DBS electrodes. Amplitude attenuation in the thalamus of intracranial volume conducted potentials with increasing distance from their cortical spike sources was measured at approximately 5-10 microV/mm. DISCUSSION: Recent reports on scalp-CM or scalp-STN EEG recordings in patients treated with DBS for epilepsy have interpreted the intracranial waveforms as evidence of transsynaptic cortical-subcortical transmission across neuroanatomical pathways presumed to be involved in the generation of sleep potentials (Clin. Neurophysiol. 113 (2002) 25) and epileptiform activity (Clin. Neurophysiol. 113 (2002) 1391). However, our results show that the intracranial spikes recorded from DBS electrodes in various regions of the thalamus (CM, AN and DM) represent subcortical volume conduction of the synchronous cortical spikes recorded with scalp EEG. The same is true for the intracranial reflections of scalp EEG sleep potentials recorded from DBS electrodes in CM, AN, DM and STN. These interictal DBS waveforms thus cannot be used to support hypotheses of specific cortical-subcortical pathways of neural propagation or subcortical generation of the DBS-recorded potentials associated with scalp EEG interictal spikes and sleep potentials. SIGNIFICANCE: Detailed analysis of the intracranial potentials recorded from DBS electrodes in association with scalp EEG spikes and sleep discharges shows that the intracranial waveforms represent volume conduction from discharges generated in the neocortex and not, as has been suggested, locally generated activity resulting from cortical-subcortical neural propagation.}, Author = {Wennberg, Richard A. and Lozano, Andres M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1388-2457}, Journal = {Clin Neurophysiol}, Keywords = {Electric Stimulation Therapy;Magnetic Resonance Imaging;Follow-Up Studies;Evoked Potentials;Humans;Middle Aged;Cortical Synchronization;Subthalamic Nucleus;Comparative Study;Electrodes;21 Epilepsy;Female;Epilepsy;Parkinson Disease;Time Factors;Male;Sleep;Thalamus;Intralaminar Thalamic Nuclei;Cerebral Cortex;21 Neurophysiology;Adult;Laterality;24 Pubmed search results 2008;Brain Mapping}, Medline = {22769878}, Month = {8}, Nlm_Id = {100883319}, Number = {8}, Organization = {Krembil Neuroscience Centre, Toronto Western Hospital, University of Toronto, 399 Bathurst Street, 5W444, Toronto, Ontario, Canada M5T 2S8. r.wennberg\@utoronto.ca}, Pages = {1403-18}, Pii = {S1388245703001524}, Pubmed = {12888022}, Title = {Intracranial volume conduction of cortical spikes and sleep potentials recorded with deep brain stimulating electrodes}, Uuid = {FD5F0AA5-85BD-422A-A226-DBE2107B0E5C}, Volume = {114}, Year = {2003}} @article{Wenzel:2001, Abstract = {Cortical dysplasia is a major cause of intractable epilepsy in children. However, the precise mechanisms linking cortical malformations to epileptogenesis remain elusive. The neuronal-specific activator of cyclin-dependent kinase 5, p35, has been recognized as a key factor in proper neuronal migration in the neocortex. Deletion of p35 leads to severe neocortical lamination defects associated with sporadic lethality and seizures. Here we demonstrate that p35-deficient mice also exhibit dysplasia/ heterotopia of principal neurons in the hippocampal formation, as well as spontaneous behavioral and electrographic seizures. Morphological analyses using immunocytochemistry, electron microscopy, and intracellular labeling reveal a high degree of abnormality in dentate granule cells, including heterotopic localization of granule cells in the molecular layer and hilus, aberrant dendritic orientation, occurrence of basal dendrites, and abnormal axon origination sites. Dentate granule cells of p35-deficient mice also demonstrate aberrant mossy fiber sprouting. Field potential laminar analysis through the dentate molecular layer reflects the dispersion of granule cells and the structural reorganization of this region. Similar patterns of cortical disorganization have been linked to epileptogenesis in animal models of chronic seizures and in human temporal lobe epilepsy. The p35-deficient mouse may therefore offer an experimental system in which we can dissect out the key morphological features that are causally related to epileptogenesis.}, Author = {Wenzel, H. J. and Robbins, C. A. and Tsai, L. H. and Schwartzkroin, P. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Animals;Astrocytes;Lysine;21 Epilepsy;Neocortex;Epilepsy;Cell Count;Hippocampus;Pyramidal Cells;Reaction Time;Disease Models, Animal;Behavior, Animal;Cytoplasmic Granules;Mossy Fibers, Hippocampal;Research Support, U.S. Gov't, P.H.S.;Nervous System Malformations;Homozygote;21 Neurophysiology;Mice, Knockout;Sensory Thresholds;Mice;Interneurons;24 Pubmed search results 2008;Immunohistochemistry;Nerve Tissue Proteins;Electroencephalography;Flurothyl;Excitatory Postsynaptic Potentials}, Medline = {21114055}, Month = {2}, Nlm_Id = {8102140}, Number = {3}, Organization = {Departments of Neurological Surgery and Physiology/Biophysics, University of Washington, Seattle, Washington 98195, USA.}, Pages = {983-98}, Pii = {21/3/983}, Pubmed = {11157084}, Title = {Abnormal morphological and functional organization of the hippocampus in a p35 mutant model of cortical dysplasia associated with spontaneous seizures}, Uuid = {18DDFD26-D5F7-4C46-9DBF-2D26E4D9F975}, Volume = {21}, Year = {2001}, url = {papers/Wenzel_JNeurosci2001.pdf}} @article{Werner:1998, Abstract = {Intercellular adhesion molecule 1 (ICAM-1, CD54) is a widely expressed glycoprotein, which plays an important role in leukocyte extravasation and in the interaction of lymphocytes with antigen-presenting cells. In the current study we examined the regulation of ICAM-1 in the mouse facial motor nucleus after facial nerve transection, using immunohistochemistry, confocal laser microscopy and electron microscopy. In the normal facial nucleus ICAM-1 immunoreactivity was restricted to vascular endothelium. Transection of the facial nerve led to a strong and selective upregulation of ICAM-1 on activated microglia. Quantitation of microglial ICAM-1 immunoreactivity revealed a biphasic increase. The first peak 1-2 days post operation paralleling the early stage of microglial activation was followed by a decline at 4-7 days. The second induction of ICAM-1 occurred at day 14 accompanying the period of neuronal cell death and microglial phagocytosis of neuronal debris. Immunoelectron microscopy showed strong ICAM-1 reactivity on the cell membrane of activated microglia at day 2. During the second peak (day 14), ICAM-1 was also observed on lymphocytes adhering to phagocytotic microglia forming aggregates around neuronal debris. No immunolabelling was observed on neurons, astrocytes or oligodendroglia. These data suggest the involvement of ICAM-1 in the adhesion of activated microglia, in their phagocytosis of neuronal debris, and also in the interaction with infiltrating lymphocytes following this injury.}, Author = {Werner, A. and Kloss, C. U. and Walter, J. and Kreutzberg, G. W. and Raivich, G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {Animals;Intercellular Adhesion Molecule-1;Fluorescent Antibody Technique;Microglia;Female;Axons;Not relevant;11 Glia;Blood-Brain Barrier;Nerve Regeneration;Facial Nerve Injuries;Support, Non-U.S. Gov't;Antibodies;Mice, Inbred Strains;Axotomy;Motor Neurons;Mice;Microscopy, Electron;Facial Nerve;Endothelium, Vascular}, Medline = {20104427}, Month = {4}, Nlm_Id = {0364620}, Number = {4}, Organization = {Department of Neuromorphology, Max-Planck Institute of Neurobiology, Martinsried, Germany.}, Pages = {219-32}, Pubmed = {10640181}, Title = {Intercellular adhesion molecule-1 (ICAM-1) in the mouse facial motor nucleus after axonal injury and during regeneration}, Uuid = {8363E845-DFB2-4CAA-9930-35E22A298D8C}, Volume = {27}, Year = {1998}} @article{Wernig:2004, Abstract = {Pluripotency and the potential for continuous self-renewal make embryonic stem (ES) cells an attractive donor source for neuronal cell replacement. Despite recent encouraging results in this field, little is known about the functional integration of transplanted ES cell-derived neurons on the single-cell level. To address this issue, ES cell-derived neural precursors exhibiting neuron-specific enhanced green fluorescent protein (EGFP) expression were introduced into the developing brain. Donor cells implanted into the cerebral ventricles of embryonic rats migrated as single cells into a variety of brain regions, where they acquired complex morphologies and adopted excitatory and inhibitory neurotransmitter phenotypes. Synaptic integration was suggested by the expression of PSD-95 (postsynaptic density-95) on donor cell dendrites, which in turn were approached by multiple synaptophysin-positive host axon terminals. Ultrastructural and electrophysiological data confirmed the formation of synapses between host and donor cells. Ten to 21 d after birth, all EGFP-positive donor cells examined displayed active membrane properties and received glutamatergic and GABAergic synaptic input from host neurons. These data demonstrate that, at the single-cell level, grafted ES cell-derived neurons undergo morphological and functional integration into the host brain circuitry. Antibodies to the region-specific transcription factors Bf1, Dlx, En1, and Pax6 were used to explore whether functional donor cell integration depends on the acquisition of a regional phenotype. Our data show that incorporated neurons frequently exhibit a lacking or ectopic expression of these transcription factors. Thus, the lack of an appropriate regional "code" does not preclude morphological and synaptic integration of ES cell-derived neurons.}, Author = {Wernig, Marius and Benninger, Felix and Schmandt, Tanja and Rade, Monika and Tucker, Kerry L. and B{\"u}ssow, Heinrich and Beck, Heinz and Br{\"u}stle, Oliver}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Survival;Cell Differentiation;Animals;Stem Cell Transplantation;Cells, Cultured;Rats;Phenotype;Synaptic Transmission;Patch-Clamp Techniques;Antigens, Differentiation;Brain;Rats, Sprague-Dawley;Cell Movement;11 Glia;Green Fluorescent Proteins;17 Transplant Regeneration;Embryo;Injections, Intraventricular;Animals, Newborn;Embryo Research;Neurons;Neurotransmitters;Mice;22 Stem cells;Genes, Reporter;Graft Survival;Luminescent Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Month = {6}, Nlm_Id = {8102140}, Number = {22}, Organization = {Institute of Reconstructive Neurobiology, University of Bonn Medical Center and Hertie Foundation, University of Bonn, D-53105 Bonn, Germany.}, Pages = {5258-68}, Pii = {24/22/5258}, Pubmed = {15175396}, Title = {Functional integration of embryonic stem cell-derived neurons in vivo}, Uuid = {ED520BE0-526C-43BF-86CA-5CB4056D31D1}, Volume = {24}, Year = {2004}, url = {papers/Wernig_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0428-04.200}} @article{West:2002, Author = {West, Anne E. and Griffith, Eric C. and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {review;research support, u.s. gov't, p.h.s. ;21 Neurophysiology;research support, non-u.s. gov't ;Signal Transduction;Humans;Animals;24 Pubmed search results 2008;Neurons;Transcription Factors}, Month = {12}, Nlm_Id = {100962781}, Number = {12}, Organization = {Division of Neuroscience, Children's Hospital, Boston, Massachusetts 02115, USA.}, Pages = {921-31}, Pii = {nrn987}, Pubmed = {12461549}, Title = {Regulation of transcription factors by neuronal activity}, Uuid = {95D225A8-CACF-4CE4-9708-4B289DAD125D}, Volume = {3}, Year = {2002}, url = {papers/West_NatRevNeurosci2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn987}} @article{Whartenby:2002, Abstract = {Fas-mediated apoptosis is a major physiologic mechanism by which activated T cells are eliminated after antigen-stimulated clonal expansion generates a specific cellular immune response. Because activated T cells are the major effectors of allograft rejection, we hypothesized that genetically modifying allogeneic bone marrow (BM) cells prior to transplantation could provide some protection from host T-cell attack, thus enhancing donor cell engraftment in bone marrow transplantation (BMT). We undertook studies to determine the outcome of lentiviral vector-mediated transduction of Fas ligand (FasL) into lineage antigen-negative (lin(-)) mouse BM cells (lin(-) BMs), in an allogeneic BMT model. FasL-modified lin(-) BMs killed Fas-expressing T cells in vitro. Mice that received transplants of allogeneic FasL(+) lin(-) BMs had enhanced short-term engraftment, after nonmyeloablative conditioning, as compared to controls. We observed no major hepatic toxicity or hematopoietic or immune impairment in recipient mice at these time points. These results suggest potential therapeutic approaches by manipulating lymphohematopoietic stem-progenitor cells to express FasL or other immune-modulating genes in the context of BMT.}, Author = {Whartenby, Katharine A. and Straley, Erin E. and Kim, Heeje and Racke, Frederick and Tanavde, Vivek and Gorski, Kevin S. and Cheng, Linzhao and Pardoll, Drew M. and Civin, Curt I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Apoptosis;Genetic Vectors;Models, Animal;Green Fluorescent Proteins;Luminescent Proteins;Gene Therapy;Listeria Infections;Animals;Lymphocyte Activation;Graft Enhancement, Immunologic;Disease Susceptibility;Tissue Donors;Base Sequence;Genes, Reporter;Mice, Inbred BALB C;Transfection;Molecular Sequence Data;Bone Marrow Transplantation;Mice, Inbred C57BL;Hematopoietic Stem Cells;Dendritic Cells;T-Lymphocytes;11 Glia;Membrane Glycoproteins;Transplantation, Homologous;Graft Survival;Radiation Chimera;Cell Lineage;Graft Rejection;Transplantation Conditioning;Recombinant Fusion Proteins;Lymphocyte Culture Test, Mixed;Mice;Lentivirus;Research Support, Non-U.S. Gov't;Mice, Transgenic}, Medline = {22271094}, Month = {11}, Nlm_Id = {7603509}, Number = {9}, Organization = {Sidney Kimmel Comprehensive Cancer Center at JHU, School of Medicine, Johns Hopkins University, Bunting-Blaustein Cancer Research Building, Room 2M44, 1650 Orleans Street, Baltimore, MD 21231, USA. whartka\@jhmi.edu}, Pages = {3147-54}, Pubmed = {12384412}, Title = {Transduction of donor hematopoietic stem-progenitor cells with Fas ligand enhanced short-term engraftment in a murine model of allogeneic bone marrow transplantation}, Uuid = {E1D27FC0-8B68-4AF5-9CAB-2EE5C9F738AE}, Volume = {100}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood-2002-01-0118}} @book{White:1989, Abstract = {88037182 Edward L. White with Asaf Keller ; introduction by Thomas A. Woolsey. ill. ; 25 cm.}, Author = {White, Edward L. and Keller, Asaf}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Isbn = {0817634029}, Keywords = {Synapses.;Cerebral cortex.;Cerebral Cortex physiology.;Cerebral Cortex anatomy &histology.;Cortex cerebral.;Neural circuitry.;Circuit neuronique.;M QP383 .W45 1989 WL 307 W583c 599/.0188}, Publisher = {Birkh{\"a}user}, Title = {Cortical circuits : synaptic organization of the cerebral cortex--structure, function, and theory}, Uuid = {8A14F8CB-1A10-4D34-88B7-10612DAA0BF9}, Year = {1989}} @article{White:2006, Abstract = {Long-term EEG monitoring in chronically epileptic animals produces very large EEG data files which require efficient algorithms to differentiate interictal spikes and seizures from normal brain activity, noise, and, artifact. We compared four methods for seizure detection based on (1) EEG power as computed using amplitude squared (the power method), (2) the sum of the distances between consecutive data points (the coastline method), (3) automated spike frequency and duration detection (the spike frequency method), and (4) data range autocorrelation combined with spike frequency (the autocorrelation method). These methods were used to analyze a randomly selected test set of 13 days of continuous EEG data in which 75 seizures were imbedded. The EEG recordings were from eight different rats representing two different models of chronic epilepsy (five kainate-treated and three hypoxic-ischemic). The EEG power method had a positive predictive value (PPV, or true positives divided by the sum of true positives and false positives) of 18\%and a sensitivity (true positives divided by the sum of true positives and false negatives) of 95\%, the coastline method had a PPV of 78\%and sensitivity of 99.59, the spike frequency method had a PPV of 78\%and a sensitivity of 95\%, and the autocorrelation method yielded a PPV of 96\%and a sensitivity of 100\%. It is possible to detect seizures automatically in a prolonged EEG recording using computationally efficient unsupervised algorithms. Both the quality of the EEG and the analysis method employed affect PPV and sensitivity.}, Author = {White, Andrew M. and Williams, Philip A. and Ferraro, Damien J. and Clark, Suzanne and Kadam, Shilpa D. and Dudek, F. Edward and Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0165-0270}, Journal = {J Neurosci Methods}, Keywords = {Telemetry;21 Epilepsy;Electroencephalography;research support, n.i.h., extramural ;21 Neurophysiology;Hippocampus;Predictive Value of Tests;Algorithms;Rats;Seizures;Models, Statistical;Kainic Acid;Animals;24 Pubmed search results 2008;Artifacts;Brain Injuries}, Month = {4}, Nlm_Id = {7905558}, Number = {1-2}, Organization = {Department of Neurology, University of Colorado Health Sciences Center, 4200 E. 9th Avenue, Denver, CO 80262, USA.}, Pages = {255-66}, Pii = {S0165-0270(05)00323-7}, Pubmed = {16337006}, Title = {Efficient unsupervised algorithms for the detection of seizures in continuous EEG recordings from rats after brain injury}, Uuid = {AF46F8B4-5EEF-4EEC-948A-FEFBA611BDDB}, Volume = {152}, Year = {2006}, url = {papers/White_JNeurosciMethods2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.jneumeth.2005.09.014}} @article{White:2001, Abstract = {Rat neural crest stem cells (NCSCs) prospectively isolated from uncultured E14.5 sciatic nerve and transplanted into chick embryos generate fewer neurons than do NCSCs isolated from E10.5 neural tube explants. In addition, they differentiate primarily to cholinergic parasympathetic neurons, although in culture they can also generate noradrenergic sympathetic neurons. This in vivo behavior can be explained, at least in part, by a reduced sensitivity of sciatic nerve-derived NCSCs to the neurogenic signal BMP2 and by the observation that cholinergic neurons differentiate at a lower BMP2 concentration than do noradrenergic neurons in vitro. These results demonstrate that neural stem cells can undergo cell-intrinsic changes in their sensitivity to instructive signals, while maintaining multipotency and self-renewal capacity. They also suggest that the choice between sympathetic and parasympathetic fates may be determined by the local concentration of BMP2. 0896-6273 Journal Article}, Author = {White, P. M. and Morrison, S. J. and Orimoto, K. and Kubu, C. J. and Verdi, J. M. and Anderson, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {10 Development;Norepinephrine/metabolism;Neurons/*cytology/drug effects/metabolism/transplantation;Animals;Cells, Cultured;Chimera;Rats;Transplantation, Heterologous;Phenotype;*Stem Cell Transplantation;Bone Morphogenetic Proteins/metabolism/pharmacology;Stem Cells/*cytology/drug effects;Cell Differentiation/drug effects/*physiology;Neurons, Afferent/cytology;Sympathetic Nervous System/cytology/embryology;Neural Crest/*cytology/embryology;Chick Embryo;Pelvis/embryology;Sciatic Nerve/cytology/embryology/transplantation;Acetylcholine/metabolism;Support, Non-U.S. Gov't;Autonomic Nervous System/cytology/embryology;Antigens, Differentiation/biosynthesis;F;Parasympathetic Nervous System/cytology/embryology}, Number = {1}, Organization = {Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA.}, Pages = {57-71}, Pubmed = {11182081}, Title = {Neural crest stem cells undergo cell-intrinsic developmental changes in sensitivity to instructive differentiation signals}, Uuid = {F02A0284-B536-45A2-BB52-8352DA667692}, Volume = {29}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11182081}} @article{Whitesides:1995, Abstract = {Prior to the emergence of the major functional subdivisions of the mammalian forebrain--the neocortex, hippocampus, olfactory bulb, basal ganglia, and basal forebrain--the lateral aspect of the telencephalic vesicle is distinguished by early neuronal differentiation assessed by MAP2 and GAP43 expression and increased expression of the Ca(2+)-independent/immunoglobulin superfamily cell adhesion molecules (CAMs) NCAM, L1, and TAG-1. In contrast, the ventral and medial aspects of the vesicle show little early neuronal differentiation and intermediate or undetectable levels of CAM expression. We asked whether cells from these three regions acquire distinct adhesive and recognition properties that reflect their position, state of neuronal differentiation, and level of CAM expression. In a dissociation/reaggregation assay, cells from the lateral telencephalic vesicle form the largest reaggregates while ventral reaggregates are of intermediate size and medial reaggregates are the smallest. This differential adhesion has a Ca(2+)-independent component, and cells in reaggregates from each region maintain expression of CAMs and other neuronal markers consistent with their region of origin. Furthermore, cells from the lateral telencephalon can specifically sort out from medial cells. Little adhesivity is observed prior to early neuronal differentiation and the expression of Ca(2+)-independent CAMs, when the forebrain is still a prosencephalic vesicle, nor does it follow the pattern of detectable CAM expression once forebrain rudiments are formed. Thus, cells in the early developing forebrain acquire distinct adhesive and recognition properties that reflect the concurrent emergence of regional differences in neuronal differentiation and CAM expression. These differences are transient and can only be detected in the telencephalic vesicle before and during the morphogenesis of rudiments of major forebrain subdivisions. eng Journal Article}, Author = {Whitesides, J. G. and LaMantia, A. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Journal = {Dev Biol}, Keywords = {Neurons/*physiology;Cell Differentiation;Tissue Distribution;*Cell Adhesion;Prosencephalon/cytology/*embryology;B abstr;Cell Separation;Animal;02 Adult neurogenesis migration;Calcium/metabolism;Stem Cells/*physiology;Support, Non-U.S. Gov't;Telencephalon/embryology;Cell Aggregation;Support, U.S. Gov't, P.H.S.;Mice;Cell Adhesion Molecules/*analysis;Immunohistochemistry}, Number = {1}, Organization = {Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA.}, Pages = {229-41.}, Title = {Distinct adhesive behaviors of neurons and neural precursor cells during regional differentiation in the mammalian forebrain}, Uuid = {D6BEF5C9-7430-45E8-8ECE-30CDCC1C94E2}, Volume = {169}, Year = {1995}} @article{Whitford:2002, Abstract = {Dendritic morphology has a profound impact on neuronal information processing. The overall extent and orientation of dendrites determines the kinds of input a neuron receives. Fine dendritic appendages called spines act as subcellular compartments devoted to processing synaptic information, and the dendritic branching pattern determines the efficacy with which synaptic information is transmitted to the soma. The acquisition of a mature dendritic morphology depends on the coordinated action of a number of different extracellular factors. Here we discuss this evidence in the context of dendritic development in the cerebral cortex. Soon after migrating to the cortical plate, neurons extend an apical dendrite directed toward the pial surface. The oriented growth of the apical dendrite is regulated by Sema3A, which acts as a dendritic chemoattractant. Subsequent dendritic development involves signaling by neurotrophic factors and Notch, which regulate dendritic growth and branching. During postnatal development the formation and stabilization of dendritic spines are regulated in part by patterns of synaptic activity. These observations suggest that extracellular signals play an important role in regulating every aspect of dendritic development and thereby exert a critical influence on cortical connectivity.}, Author = {Whitford, Kristin L. and Dijkhuizen, Paul and Polleux, Franck and Ghosh, Anirvan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {0147-006X}, Journal = {Annu Rev Neurosci}, Keywords = {Nerve Growth Factors;24 Pubmed search results 2008;Cell Differentiation;Dendrites;Research Support, Non-U.S. Gov't;Cell Communication;Pyramidal Cells;Research Support, U.S. Gov't, P.H.S.;Synaptic Transmission;Animals;Humans;Cerebral Cortex;review;Chemotaxis}, Medline = {22047053}, Nlm_Id = {7804039}, Organization = {Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. kwhit\@jhmi.edu}, Pages = {127-49}, Pii = {112701.142932}, Pubmed = {12052906}, Title = {Molecular control of cortical dendrite development}, Uuid = {F7DC6E52-CE7C-4DDF-BE1A-C9DDEA633500}, Volume = {25}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1146/annurev.neuro.25.112701.142932}} @article{Whiting:1999, Abstract = {Disorders of cortical development form a spectrum of lesions produced by insults to the developing neocortex. These conditions typically first manifest in childhood with epilepsy, developmental delay, and focal neurologic signs. Although the clinical and electrophysiologic findings are often nonspecific, high-resolution magnetic resonance imaging facilitates diagnosis during life, and assists in delineating specific clinical syndromes. While many patients are dysmorphic and severely affected by mental retardation and epilepsy, some have normal or near-normal cognitive function and no seizures. Molecular studies of dysplastic cortex are providing new insights into the basic mechanisms of brain function and development, while pathologic analysis of tissue removed at surgery is helping to define epileptic circuitry. Treatment of the epilepsy associated with cortical dysplasia is often frustrating, but surgical approaches based on accurately defining epileptogenic regions are proving increasingly successful. Genetic diagnosis is important for accurate counseling of families.}, Author = {Whiting, S. and Duchowny, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0883-0738}, Journal = {J Child Neurol}, Keywords = {10 Development;Genetic Screening;Syndrome;Child, Preschool;Humans;review;Female;Epilepsy;Infant;Child;Mental Retardation;Brain Diseases;Male;Developmental Disabilities;10 genetics malformation;Cerebral Cortex;Genetic Counseling;Infant, Newborn;24 Pubmed search results 2008;Cognition Disorders}, Month = {12}, Nlm_Id = {8606714}, Number = {12}, Organization = {Department of Pediatrics, University of Ottawa and Children's Hospital of Eastern Ontario, Canada. whiting\@cheo.on.ca}, Pages = {759-71}, Pubmed = {10614562}, Title = {Clinical spectrum of cortical dysplasia in childhood: diagnosis and treatment issues}, Uuid = {33F53B1E-941D-45B1-B1AC-1E9B1D5BDE91}, Volume = {14}, Year = {1999}} @article{Whitman:2007, Abstract = {The adult mammalian olfactory bulb (OB) receives a continuing influx of new interneurons. Neuroblasts from the subventricular zone (SVZ) migrate into the OB and differentiate into granule cells and periglomerular cells that are presumed to integrate into the synaptic circuits of the OB. We have used retroviral infection into the SVZ of mice to label adult-generated granule cells and follow their differentiation and integration into OB circuitry. Using synaptic markers and electron microscopy, we show new granule cells integrating into the reciprocal circuitry of the external plexiform layer (EPL), beginning at 21 d postinfection (dpi). We further show that synapses are formed earlier, beginning at 10 dpi, on the somata and basal dendrites of new cells in the granule cell layer (GCL), before dendritic elaboration in the EPL. In the EPL, elaborate dendritic arbors with spines are first evident at 14 dpi. The density of spines increases from 14 to 28 dpi, and then decreases by 56 dpi. Despite the initial appearance of dendritic spines at 14 dpi in the EPL, no expression of presynaptic or postsynaptic markers is seen until 21 dpi. These data suggest that adult-generated granule cells are first innervated by centrifugal or mitral/tufted cell axon collaterals in the GCL and that these inputs may contribute to their differentiation, maturation, and synaptic integration into the dendrodendritic local circuits found in the EPL.}, Author = {Whitman, Mary C. and Greer, Charles A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {8102140}, Number = {37}, Organization = {Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.}, Pages = {9951-61}, Pii = {27/37/9951}, Pubmed = {17855609}, Title = {Synaptic integration of adult-generated olfactory bulb granule cells: basal axodendritic centrifugal input precedes apical dendrodendritic local circuits}, Uuid = {7DC228E5-D617-4DDA-8D9F-9B05C5D96B2C}, Volume = {27}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1633-07.2007}} @article{Whittaker:2000, Abstract = {Because many viruses replicate in the nucleus of their host cells, they must have ways of transporting their genome and other components into and out of this compartment. For the incoming virus particle, nuclear entry is often one of the final steps in a complex transport and uncoating program. Typically, it involves recognition by importins (karyopherins), transport to the nucleus, and binding to nuclear pore complexes. Although all viruses take advantage of cellular signals and factors, viruses and viral capsids vary considerably in size, structure, and in how they interact with the nuclear import machinery. Influenza and adenoviruses undergo extensive disassembly prior to genome import; herpesviruses release their genome into the nucleus without immediate capsid disassembly. Polyoma viruses, parvoviruses, and lentivirus preintegration complexes are thought to enter in intact form, whereas the corresponding complexes of onco-retroviruses have to wait for mitosis because they cannot infect interphase nuclei. 1081-0706 Journal Article Review Review, Academic}, Author = {Whittaker, G. R. and Kann, M. and Helenius, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Annu Rev Cell Dev Biol}, Keywords = {J pdf;Viruses/*pathogenicity;Nuclear Envelope/virology;Human;Cytoplasm/virology;15 Retrovirus mechanism;Animals;*Viral Physiology;Cell Nucleus/*virology}, Organization = {Department of Microbiology and Immunology, Cornell University, Ithaca New York, USA. grw7\@cornell.edu}, Pages = {627-51}, Pubmed = {11031249}, Title = {Viral entry into the nucleus}, Uuid = {9F8ACD09-1E43-409D-B6C5-6C2018B9523E}, Volume = {16}, Year = {2000}, url = {papers/Whittaker_AnnuRevCellDevBiol2000.pdf}} @article{Whittaker:1998, Abstract = {Many viruses replicate in the nucleus of their animal and plant host cells. Nuclear import, export, and nucleo-cytoplasmic shuttling play a central role in their replication cycle. Although the trafficking of individual virus proteins into and out of the nucleus has been well studied for some virus systems, the nuclear transport of larger entities such as viral genomes and capsids has only recently become a subject of molecular analysis. In this review, the general concepts emerging are discussed and a survey is provided of current information on both plant and animal viruses. Summarizing the main findings in this emerging field, it is evident that most viruses that enter or exit the nucleus take advantage of the cell's nuclear import and export machinery. With a few exceptions, viruses seem to cross the nuclear envelope through the nuclear pore complexes, making use of cellular nuclear import and export signals, receptors, and transport factors. In many cases, they capitalize on subtle control systems such as phosphorylation that regulate traffic of cellular components into and out of the nucleus. The large size of viral capsids and their composition (they contain large RNA and DNA molecules for which there are few precedents in normal nuclear transport) make the processes unique and complicated. Prior capsid disassembly (or deformation) is required before entry of viral genomes and accessory proteins can occur through nuclear pores. Capsids of different virus families display diverse uncoating programs which culminate in genome transfer through the nuclear pores. 0042-6822 Journal Article Review Review, Tutorial}, Author = {Whittaker, G. R. and Helenius, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Virology}, Keywords = {Plant Viruses/physiology;Virus Replication/*physiology;*Genome, Viral;J pdf;Molecular Sequence Data;Amino Acid Sequence;Support, U.S. Gov't, P.H.S.;15 Retrovirus mechanism;Animals;Cell Nucleus/*virology}, Number = {1}, Organization = {Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. grw7\@cornell.edu}, Pages = {1-23}, Pubmed = {9656989}, Title = {Nuclear import and export of viruses and virus genomes}, Uuid = {BE1C80A7-A056-477B-B27D-44B73B6780B5}, Volume = {246}, Year = {1998}, url = {papers/Whittaker_Virology1998.pdf}} @article{Whittemore:1999, Abstract = {The effects of specific mitogens and substrates on the proliferative capacity and the differentiated phenotypic plasticity of neural precursor cell populations isolated from the adult rat subventricular zone (SVZ) were examined. SVZ cells were grown on uncoated tissue culture plastic, extracellular matrix, or poly-D-ornithine with either laminin or fibronectin. SVZ neural precursor cells could not be generated with platelet-derived growth factor (PDGF), granulocyte macrophage colony stimulating factor, stem cell factor, heparin-binding epidermal growth factor (HB-EGF), granulocyte colony stimulating factor, or ciliary neurotrophic factor (CNTF), but could be with EGF, fibroblast growth factor 2 (FGF2), and FGF2 plus heparin. Varying combinations of substrate and mitogen resulted in very different expansion rates and/or lineage potential. Neurons, oligodendrocytes, and astrocytes differentiated from all cultures, but EGF-generated neural precursor cells were more restricted to an astrocytic lineage and FGF2-generated neural precursor cells had a greater capacity for neuronal differentiation. In both EGF- and FGF2-generated cell populations, CNTF increased the number of differentiated astrocytes, triiodothyronine oligodendrocytes, PDGF neurons, and brain-derived neurotrophic factor neurons only from EGF cells. Electrophysiological analysis of differentiated cells showed three distinct phenotypes, glial, neuronal, and presumed precursor cells, although the neuronal properties were immature. Collectively, these data indicate that CNS neural precursor cell populations isolated with different mitogens and substrates are intrinsically different and their characteristics cannot be directly compared. 0014-4827 Journal Article}, Author = {Whittemore, S. R. and Morassutti, D. J. and Walters, W. M. and Liu, R. H. and Magnuson, D. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Exp Cell Res}, Keywords = {Neuroglia/cytology/drug effects/physiology;Heparin/pharmacology;Cell Differentiation/drug effects;Electrophysiology;Lateral Ventricles/*cytology;In Vitro;Animals;Rats;Phenotype;C abstr;Fibronectins/pharmacology;Epidermal Growth Factor/pharmacology;Support, Non-U.S. Gov't;Neurons/*cytology/*drug effects/physiology;Growth Substances/pharmacology;04 Adult neurogenesis factors;Fibroblast Growth Factor 2/pharmacology;Support, U.S. Gov't, P.H.S.;Mitogens/*pharmacology;Stem Cells/*cytology/*drug effects/physiology;Cell Division/drug effects}, Number = {1}, Organization = {The Miami Project, University of Miami School of Medicine, Miami, Florida 33136, USA. swhittemore\@louisville.edu}, Pages = {75-95}, Pubmed = {10502401}, Title = {Mitogen and substrate differentially affect the lineage restriction of adult rat subventricular zone neural precursor cell populations}, Uuid = {87F9709C-B9EA-4886-AF23-B15036754FEA}, Volume = {252}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10502401}} @article{Wichterle:2001, Abstract = {Recent studies suggest that neurons born in the developing basal forebrain migrate long distances perpendicularly to radial glia and that many of these cells reach the developing neocortex. This form of tangential migration, however, has not been demonstrated in vivo, and the sites of origin, pathways of migration and final destinations of these neurons in the postnatal brain are not fully understood. Using ultrasound-guided transplantation in utero, we have mapped the migratory pathways and fates of cells born in the lateral and medial ganglionic eminences (LGE and MGE) in 13.5-day-old mouse embryos. We demonstrate that LGE and MGE cells migrate along different routes to populate distinct regions in the developing brain. We show that LGE cells migrate ventrally and anteriorly, and give rise to the projecting medium spiny neurons in the striatum, nucleus accumbens and olfactory tubercle, and to granule and periglomerular cells in the olfactory bulb. By contrast, we show that the MGE is a major source of neurons migrating dorsally and invading the developing neocortex. MGE cells migrate into the neocortex via the neocortical subventricular zone and differentiate into the transient subpial granule neurons in the marginal zone and into a stable population of GABA-, parvalbumin- or somatostatin-expressing interneurons throughout the cortical plate. 0950-1991 Journal Article}, Author = {Wichterle, H. and Turnbull, D. H. and Nery, S. and Fishell, G. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {Development}, Keywords = {Cell Transplantation/methods;Human;Cell Differentiation;Embryonic Induction;Animals;Female;Cell Movement;H pdf;Mice, Transgenic;Cerebral Cortex/cytology/embryology;*Neurons/metabolism/transplantation;Phosphoproteins/metabolism;Prosencephalon/*cytology/*embryology;Mice, Inbred Strains;Support, Non-U.S. Gov't;Ultrasonography, Prenatal;Somatostatin/metabolism;Support, U.S. Gov't, Non-P.H.S.;Olfactory Bulb/cytology/embryology;Support, U.S. Gov't, P.H.S.;Mice;gamma-Aminobutyric Acid/metabolism;Parvalbumins/metabolism;Ganglia/cytology/embryology/transplantation;Telencephalon/cytology/embryology;Neuroglia/cytology;12 Interneuron development}, Number = {19}, Organization = {The Rockefeller University, New York, NY 10021, USA.}, Pages = {3759-71}, Title = {In utero fate mapping reveals distinct migratory pathways and fates of neurons born in the mammalian basal forebrain}, Uuid = {790C19A6-4934-4A7D-A31F-03FC919CA6A5}, Volume = {128}, Year = {2001}, url = {papers/Wichterle_Development2001.pdf}} @article{Wichterle:1999, Abstract = {In this study, we identified neuronal precursors that can disperse through adult mammalian brain tissue. Transplanted neuronal precursors from embryonic medial ganglionic eminence (MGE), but not from lateral ganglionic eminence (LGE) or neocortex, dispersed and differentiated into neurons in multiple adult brain regions. In contrast, only LGE cells were able to migrate efficiently from the adult subventricular zone to the olfactory bulb. In embryonic brain slices, MGE cells migrated extensively toward cortex. Our results demonstrate that cells in different germinal regions have unique migratory potentials, and that adult mammalian brain can support widespread dispersion of specific populations of neuronal precursors. These findings could be useful in repair of diffuse brain damage.}, Author = {Wichterle, H. and Garcia-Verdugo, J. M. and Herrera, D. G. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Nat Neurosci}, Keywords = {H;Mice, Inbred Strains;Corpus Striatum/cytology;Neurons/*transplantation;Stem Cells/*transplantation;Median Eminence/cytology/*embryology;Lac Operon;Olfactory Bulb/cytology;Neocortex/cytology;Animal;Support, U.S. Gov't, P.H.S.;12 Interneuron development;*Fetal Tissue Transplantation;Support, Non-U.S. Gov't;Mice;Cell Movement;*Brain Tissue Transplantation}, Number = {5}, Organization = {Rockefeller University, New York, New York 10021, USA. wichteh\@rockvax.rockefeller.edu}, Pages = {461-6.}, Title = {Young neurons from medial ganglionic eminence disperse in adult and embryonic brain}, Uuid = {54FAB3EF-AFE2-41B3-AE74-2EF1AEB186A3}, Volume = {2}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10321251}} @article{Wichterle:1997, Abstract = {Neuronal precursors born in the subventricular zone (SVZ) of the neonatal and adult rodent brain migrate 3-8 mm from the walls of the lateral ventricle into the olfactory bulb. This tangentially oriented migration occurs without the guidance of radial glia or axonal processes. The cells move closely associated, forming elongated aggregates called chains, which are ensheathed by astrocytes. We have developed a culture system in which postnatal mouse SVZ neuronal precursors assemble into chains with ultrastructural and immunocytochemical characteristics equivalent to those in vivo but without the astrocytic sheath. Time-lapse videomicrography revealed that individual cells migrate along the chains very rapidly (approximately 122 microm/hr) in both directions. Periods of cell body translocation were interspersed with stationary periods. This saltatory behavior was similar to radial glia-guided migration but approximately 4 times faster. Neuronal precursors isolated from embryonic cortical ventricular zone or cerebellar external granule layer did not form chains under these conditions, suggesting that chain migration is characteristic of SVZ precursors. This study directly demonstrates that SVZ neuronal precursors migrate along each other without the assistance of astrocytes or other cell types. (Additional data are presented in www.cell.com).}, Author = {Wichterle, H. and Garcia-Verdugo, J. M. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {Fluorescent Dyes;Microscopy, Video;B abstr;Cells, Cultured;Cell Movement/*physiology;Animal;02 Adult neurogenesis migration;Astrocytes/physiology;Support, Non-U.S. Gov't;Neurons/chemistry/*cytology/ultrastructure;Extracellular Matrix/physiology;Mice, Inbred Strains;Brain/cytology/embryology;Support, U.S. Gov't, P.H.S.;Carbocyanines;Stem Cells/chemistry/*cytology/ultrastructure;Mice;Immunohistochemistry;Microscopy, Electron;Cerebral Ventricles/cytology}, Number = {5}, Organization = {The Rockefeller University, New York, New York 10021, USA.}, Pages = {779-91.}, Title = {Direct evidence for homotypic, glia-independent neuronal migration}, Uuid = {68C2F1F3-B3ED-4148-A874-22691E6B9830}, Volume = {18}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9182802}} @article{Wichterle:2003, Abstract = {Young neurons born in the medial ganglionic eminence (MGE) migrate a long distance dorsally, giving rise to several types of interneurons in neocortex. The mechanisms that facilitate selective dorsal dispersion of MGE cells while restricting their movement ventrally into neighboring regions are not known. Using microtransplantation into fetal brain slices and onto dissociated substrate cells on floating filters (spot assay), we demonstrate that ventral forebrain regions neighboring the MGE are nonpermissive for MGE cell migration, whereas the dorsal regions leading to the neocortex are increasingly permissive. Spot assay experiments using filters with different pore sizes indicate that the permissive factors are not diffusible. We also show that MGE cells respond to chemoattractive and inhibitory factors diffusing from the neocortex and ventromedial forebrain, respectively. We propose that the final extent and regional specificity of MGE cell dispersion is largely dictated by contact guidance through a selectively permissive environment, flanked by nonpermissive tissues. In addition, we propose that chemotactic guidance cues superimposed over the permissive corridor facilitate efficient dorsal migration of MGE cells. 0027-8424 Journal Article}, Author = {Wichterle, H. and Alvarez-Dolado, M. and Erskine, L. and Alvarez-Buylla, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {H;Chemotaxis;Nerve Tissue Proteins/physiology;Median Eminence/*cytology;Support, U.S. Gov't, P.H.S.;12 Interneuron development;Neocortex/*cytology;Animals;Support, Non-U.S. Gov't;Diffusion;Mice;Cell Movement}, Number = {2}, Organization = {The Rockefeller University, New York, NY 10021, USA.}, Pages = {727-32}, Pubmed = {12515855}, Title = {Permissive corridor and diffusible gradients direct medial ganglionic eminence cell migration to the neocortex}, Uuid = {93DD9D9F-BB17-4DE4-B726-A9D1FCACDBF2}, Volume = {100}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12515855}} @article{Wickelgren:2002, Abstract = {1095-9203 News}, Author = {Wickelgren, I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Journal = {Science}, Keywords = {Neurons/*physiology;Human;Animals;Stem Cell Transplantation;Spinal Nerves/*physiology;Cyclic AMP/metabolism/therapeutic use;Chondroitin ABC Lyase/metabolism/therapeutic use;Recovery of Function;Stem Cells/physiology;Growth Substances/therapeutic use;Myelin Proteins/genetics/immunology/metabolism;Receptors, Cell Surface/antagonists &inhibitors/metabolism;Myelin-Associated Glycoprotein/metabolism;Olfactory Mucosa/cytology;Clinical Trials;01 Adult neurogenesis general;Neuroglia/physiology/transplantation;Methylprednisolone/therapeutic use;Spinal Cord Injuries/drug therapy/surgery/*therapy;Growth Inhibitors/antagonists &inhibitors/metabolism;Neuroprotective Agents/therapeutic use;*Nerve Regeneration;4-Aminopyridine/therapeutic use;Combined Modality Therapy;A both}, Number = {5579}, Pages = {178-81}, Title = {Neuroscience. Animal studies raise hopes for spinal cord repair}, Uuid = {26798064-237E-4B42-97C7-8E3669ED064C}, Volume = {297}, Year = {2002}} @article{Wienecke:1997, Abstract = {The tuberous sclerosis-2 (TSC2) gene is linked to tuberous sclerosis (TSC), a dominantly inherited genetic syndrome in which inactivation of the normal TSC2 allele is associated with the development of mostly benign tumors and focal dysplasias. TSC2 encodes the protein tuberin, which is a widely expressed 180-kd polypeptide that exhibits specific GTPase activating activity toward Rap1 in vitro and co-localizes with Rap1 in cultured cells. In this study, we have performed immunohistochemical analyses, using affinity-purified anti-tuberin antibodies, to study the distribution of tuberin in a panel of normal human organs that are commonly affected by TSC. Cryosections indicated that tuberin is widely expressed at low levels. More intense staining of tuberin, in the cryosections and in paraffin sections, was observed in the small blood vessels of many organs, including the kidney, skin, and adrenal gland. High levels of tuberin were also detected in cortical neurons and cerebellar Purkinje cells. These findings imply that loss-of-function mutations in TSC2 might lead to the development of highly vascularized tumors, subcortical tubers, and focal atrophy of the cerebellar cortex, which are features commonly associated with TSC. Moreover, Rap1 was also found to be highly expressed in many of the same cells that contained high levels of tuberin, suggesting a functional interaction between tuberin and Rap1 in these tissues.}, Author = {Wienecke, R. and Maize, J. C. and Reed, J. A. and de Gunzburg, J. and Yeung, R. S. and DeClue, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Tuberous Sclerosis;Tumor Suppressor Proteins;10 Development;research support, non-u.s. gov't;Repressor Proteins;Immunohistochemistry;GTP-Binding Proteins;rap GTP-Binding Proteins;10 genetics malformation;Myocardium;Kidney;Skin;Humans;Cerebral Cortex;24 Pubmed search results 2008;Genes, Tumor Suppressor}, Month = {1}, Nlm_Id = {0370502}, Number = {1}, Organization = {Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland 20892, USA.}, Pages = {43-50}, Pubmed = {9006320}, Title = {Expression of the TSC2 product tuberin and its target Rap1 in normal human tissues}, Uuid = {50EEB9BC-434D-4103-9BDE-C26A04DC263E}, Volume = {150}, Year = {1997}} @article{Wierenga:2005, Abstract = {Synaptic scaling is a form of homeostatic plasticity that scales synaptic strengths up or down to compensate for prolonged changes in activity. It has been controversial whether this plasticity is expressed presynaptically, postsynaptically, or both. Here we describe in detail the homeostatic changes that take place at excitatory synapses in visual cortical cultures after 1 or 2 d of activity blockade. After 7-10 d in vitro, activity blockade significantly increased postsynaptic accumulation of synaptic AMPA receptors via proportional increases in glutamate receptor 1 (GluR1) and GluR2. Time-lapse imaging of enhanced green fluorescent protein-tagged AMPA receptors revealed that receptor accumulation increased progressively over 2 d of activity blockade and affected the entire population of imaged synapses. The strength of synaptic connections between pyramidal neurons was more than doubled after activity blockade without affecting short-term depression or the coefficient of variation of the postsynaptic responses. Furthermore, uptake of the fluorescent styryl dye FM1-43 (N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl] pyridinium dibromide) by presynaptic terminals was not different at control and activity-blocked synapses. In addition to the increased accumulation of postsynaptic AMPA receptors, boosting of dendritic AMPA currents by sodium channels was increased by activity blockade. These data indicate that, at young neocortical synapses, synaptic scaling has a predominantly postsynaptic locus and functions as a gain control mechanism to regulate neuronal activity without affecting the dynamics of synaptic transmission.}, Author = {Wierenga, Corette J. and Ibata, Keiji and Turrigiano, Gina G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Diagnostic Imaging;research support, non-u.s. gov't ;24 Pubmed search results 2008;Immunohistochemistry;Lysine;tau Proteins;Animals;Cells, Cultured;research support, u.s. gov't, p.h.s. ;Quaternary Ammonium Compounds;Rats, Long-Evans;comparative study ;Transfection;Electric Stimulation;Synapses;Homeostasis;research support, n.i.h., extramural ;Neocortex;Neuronal Plasticity;Potassium Chloride;Action Potentials;Synapsins;Tetrodotoxin;Time Factors;Rats;Patch-Clamp Techniques;Receptors, AMPA;Intracellular Signaling Peptides and Proteins;Animals, Newborn;21 Neurophysiology;Membrane Proteins;Neurons;Pyridinium Compounds}, Month = {3}, Nlm_Id = {8102140}, Number = {11}, Organization = {Department of Biology and Center for Complex Systems, Brandeis University, Waltham, Massachusetts 02454-9110, USA.}, Pages = {2895-905}, Pii = {25/11/2895}, Pubmed = {15772349}, Title = {Postsynaptic expression of homeostatic plasticity at neocortical synapses}, Uuid = {DD1E2252-533D-4DF7-91DA-88EE26560DC5}, Volume = {25}, Year = {2005}, url = {papers/Wierenga_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.5217-04.2005}} @article{Wilairat:1978, Abstract = {0024-3205 Journal Article}, Author = {Wilairat, P. and Yuthavong, Y. and Khungvanlert, R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Life Sci}, Keywords = {Erythrocytes/cytology/*drug effects;Female;EE, DMSO, abstr;08 Aberrant cell cycle;In Vitro;Cell Fusion/drug effects;Erythrocyte Membrane/metabolism;Dimethyl Sulfoxide/*pharmacology;Chickens;Animals}, Number = {22}, Pages = {1993-7}, Pubmed = {672441}, Title = {Effect of membrane modification on cell fusion of hen erythrocytes induced by dimethyl sulfoxide}, Uuid = {0AD45407-4683-469F-8405-9EE6D1CA4649}, Volume = {22}, Year = {1978}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=672441}} @article{Wilbrecht:2002, Abstract = {It is not known whether the addition of new neurons to the high vocal center (HVC) of juvenile zebra finches permits vocal learning or is the consequence of it. To tease apart these two, we performed surgery on 26- d-old juveniles. The operations were removal of both cochleae and unilateral or bilateral denervation of the syrinx. Ability to imitate a tutor song was little affected by unilateral syringeal denervation but was severely hindered by bilateral denervation or deafening. Recruitment of new HVC neurons was studied by injecting BrdU, a cell birth marker, on post-hatching days 61-65 and killing the animals 30 d later. Deafening or bilateral denervation did not alter the number of BrdU-labeled neurons in HVC, but unilateral denervation nearly doubled this number in the intact side. This doubling was transient, was blocked by deafening, and was not seen in birds that received BrdU injections earlier or later in vocal ontogeny. The adult number of HVC neurons was not affected by any of our surgical procedures. Apparently experience does not affect the total number of neurons in adult HVC, but some kinds of experience can, during narrowly defined times, influence the recruitment of new HVC neurons.}, Author = {Wilbrecht, L. and Crionas, A. and Nottebohm, F.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:34 -0400}, Journal = {J Neurosci}, Keywords = {Drug Administration Schedule;Larynx/physiology;Songbirds;Neurons/cytology/*physiology;Deafness/physiopathology;Denervation;Cell Count;Animal;Brain/cytology/*physiology;Bromodeoxyuridine/administration &dosage/pharmacokinetics;Time Factors;Hearing/physiology;Male;01 Adult neurogenesis general;Support, Non-U.S. Gov't;Cochlea/innervation/physiology;Recruitment (Neurology)/*physiology;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Vocalization, Animal/*physiology;Learning/*physiology;A both}, Number = {3}, Organization = {Laboratory of Animal Behavior, The Rockefeller University, New York, New York 10021, USA. wilbrel\@mail.rockefeller.edu.}, Pages = {825-31.}, Title = {Experience affects recruitment of new neurons but not adult neuron number}, Uuid = {99281C19-47C0-46B6-A552-A6D2BB070917}, Volume = {22}, Year = {2002}, url = {papers/Wilbrecht_JNeurosci2002.pdf}} @article{Wilcott:1981, Author = {Wilcott, R. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0031-9384}, Journal = {Physiol Behav}, Keywords = {Rats;Inhibition (Psychology);Animals;Male;24 Pubmed search results 2008;Frontal Lobe}, Medline = {82060710}, Month = {8}, Nlm_Id = {0151504}, Number = {2}, Pages = {237-41}, Pubmed = {7301955}, Title = {Medial and orbital cortex and the suppression of behavior in the rat}, Uuid = {82222793-7DDD-48BC-ADCD-B0A129F04C22}, Volume = {27}, Year = {1981}} @article{Wilder:1965, Author = {Wilder, B. J. and Schmidt, R. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Epilepsy;Electroencephalography;21 Neurophysiology;Haplorhini;Animals;Cerebral Cortex;21 Epilepsy;24 Pubmed search results 2008}, Medline = {66108218}, Month = {12}, Nlm_Id = {2983306R}, Number = {4}, Pages = {297-309}, Pubmed = {4956069}, Title = {Propagation of epileptic discharge from chronic neocortical foci in monkey}, Uuid = {198B7D99-24F2-42F9-A765-5B72F4C3925B}, Volume = {6}, Year = {1965}} @article{Wilkinson:2001, Abstract = {The control of cell movement during development is essential for forming and stabilizing the spatial organization of tissues and cell types. During initial steps of tissue patterning, distinct regional domains or cell types arise at appropriate locations, and the movement of cells is constrained in order to maintain spatial relationships during growth. In other situations, the guidance of migrating cells or neuronal growth cones to specific destinations underlies the establishment or remodeling of a pattern. Eph receptor tyrosine kinases and their ephrin ligands are key players in controlling these cell movements in many tissues and at multiple stages of patterning.}, Author = {Wilkinson, D. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Neurons;Receptor Protein-Tyrosine Kinases;10 Development;Ligands;Membrane Proteins;Signal Transduction;10 circuit formation;Growth Cones;Receptor, EphA1;Body Patterning;Nervous System;Animals;Cell Movement;24 Pubmed search results 2008;review;Axons}, Month = {3}, Nlm_Id = {100962781}, Number = {3}, Organization = {Division of Developmental Neurobiology, National Institute for Medical Research, Ridgeway, Mill Hill, London NW7 1AA, UK. dwilkin\@nimr.mrc.ac.uk}, Pages = {155-64}, Pubmed = {11256076}, Title = {Multiple roles of EPH receptors and ephrins in neural development}, Uuid = {F526E1A8-2B4D-447B-859D-D14D0691868F}, Volume = {2}, Year = {2001}} @article{Willhite:2006, Abstract = {Olfactory sensory neurons converge onto glomeruli in the olfactory bulb (OB) to form modular information processing units. Similar input modules are organized in translaminar columns for other sensory modalities. It has been less clear in the OB whether the initial modular organization relates to a columnar structure in the deeper layers involved in local circuit processing. To probe synaptic connectivity in the OB, we injected a retrograde-specific strain of the pseudorabies virus into the rat OB and piriform cortex. The viral-staining patterns revealed a striking columnar organization that extended across all layers of the OB from the glomeruli to the deep granule cell layer. We hypothesize that the columns represent an extension of the glomerular unit. Specific patterning was observed, suggesting selective, rather than distance-dependent, center-surround connectivity. The results provide a previously undescribed basis for interpreting the synaptic connections between mitral and granule cells within the context of a columnar organization in the OB and have implications for olfactory coding and network organization.}, Author = {Willhite, David C. and Nguyen, Katherine T. and Masurkar, Arjun V. and Greer, Charles A. and Shepherd, Gordon M. and Chen, Wei R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Synapses;Rats, Sprague-Dawley;research support, n.i.h., extramural ;Immunohistochemistry;Rats;Herpesvirus 1, Suid;Olfactory Bulb;Neurons, Afferent;Animals;Biological Transport;13 Olfactory bulb anatomy;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {33}, Organization = {Department of Neurobiology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA. david.willhite\@yale.edu}, Pages = {12592-7}, Pii = {0602032103}, Pubmed = {16895993}, Title = {Viral tracing identifies distributed columnar organization in the olfactory bulb}, Uuid = {EEAD06C3-9F1B-4A08-9ACA-8D75CC814370}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0602032103}} @article{Williams:2002, Abstract = {Brain perivascular macrophages are a major target of simian immunodeficiency virus (SIV) infection in rhesus macaques and HIV infection in humans. Perivascular macrophages are distinct from parenchymal microglia in their location, morphology, expression of myeloid markers, and turnover in the CNS. In contrast to parenchymal microglia, perivascular macrophages are continuously repopulated by blood monocytes, which undergo maturation to macrophages on entering the central nervous system (CNS). We studied differences in monocyte/macrophages in vivo that might account for preferential infection of perivascular macrophages by SIV. In situ hybridization for SIV and proliferating cellular nuclear antigen (PCNA) immunohistochemistry demonstrated that SIV-infected and PCNA-positive cells were predominantly found in perivascular cuffs of viremic animals and in histopathological lesions that characterize SIV encephalitis (SIVE) in animals with AIDS. Multilabel techniques including double-label immunohistochemistry and combined in situ hybridization and immunofluorescence confocal microscopy revealed numerous infected perivascular macrophages that were PCNA-positive. Outside the CNS, SIV-infected, PCNA-expressing macrophage subpopulations were found in the small intestine and lung of animals with AIDS. While PCNA is used as a marker of cell proliferation it is also strongly expressed in non-dividing cells undergoing DNA synthesis and repair. Therefore, more specific markers for cell proliferation including Ki-67, topoisomerase IIalpha, and bromodeoxyuridine (BrdU) incorporation were used which indicated that PCNA-positive cells within SIVE lesions were not proliferating. These observations are consistent with perivascular macrophages as terminally differentiated, non-dividing cells and underscores biological differences that could potentially define mechanisms of preferential, productive infection of perivascular macrophages in the rhesus macaque model of neuroAIDS. These studies suggest that within CNS and non-CNS tissues there exist subpopulations of macrophages that are SIV-infected and express PCNA.}, Author = {Williams, Kenneth and Schwartz, Annette and Corey, Sarah and Orandle, Marlene and Kennedy, William and Thompson, Brendon and Alvarez, Xavier and Brown, Charlie and Gartner, Suzanne and Lackner, Andrew}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Research Support, Non-U.S. Gov't;Macaca mulatta;Research Support, U.S. Gov't, P.H.S.;Proliferating Cell Nuclear Antigen;Simian Acquired Immunodeficiency Syndrome;Cell Division;11 Glia;Macrophages;SIV;Animals;Brain}, Medline = {22152816}, Month = {8}, Nlm_Id = {0370502}, Number = {2}, Organization = {Department of Medicine, Harvard Medical School, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. kenneth\_williams\@hms.harvard.edu}, Pages = {575-85}, Pubmed = {12163382}, Title = {Proliferating cellular nuclear antigen expression as a marker of perivascular macrophages in simian immunodeficiency virus encephalitis}, Uuid = {4DD489F8-29A6-47A0-BCCA-F1111CBD6864}, Volume = {161}, Year = {2002}} @article{Williams:1998, Abstract = {The dopaminergic innervation of the frontal cortex, commonly implicated in psychiatric and neurological disorders, has traditionally been associated with a circumscribed midline group of ventral tegmental area (VTA) neurons. We have employed a combination of retrograde tracing, using fluorescent dyes, and tyrosine hydroxylase (TH) immunohistochemistry to amplify knowledge of frontal cortex-projecting dopamine (DA) neurons in non-human primates. Injections of retrograde fluorochromes were made in areas 46, 8B/6M, 12, 4, 24, and the prelimbic (PL) and infralimbic areas (IL) of the rhesus monkey. The mesencephalic distribution of neurons exhibiting both retrograde labeling and TH immunoreactivity or retrograde labeling alone was examined from the level of the mammillary bodies to the locus coeruleus. DA afferents innervating the macaque frontal cortex as a whole originate from an unexpectedly widespread continuum of neurons distributed in the dorsal aspects of all three of the mesencephalic DA cell groups [A9, A10 and A8; generally corresponding to the DA cells of the substantia nigra (SN), VTA, and the retrorubral area (RRA) respectively]. A large number of these retrogradely labeled neurons are non-dopaminergic. The dorsal frontal cortex (areas 46, BB/6M and 4) receive DA projections primarily from the full medial-lateral extent of A9 cells dorsal to the SN pars compacta (i.e. A9 dorsalis), the RRA and to a lesser extent from the A10 parabrachial pigmented nucleus (PBPG) and linear nuclei, the latter of which have been associated with the mesocortical DA system. In contrast, the ventromedial PL and IL exhibit a significantly more robust input from the PBPG and midline linear VTA nuclei than from the lateral groups. The anterior cingulate cortex (area 24) is innervated by a group of DA neurons primarily located between these laterally and medially concentrated populations. These findings demonstrate a degree of compartmentalization of the mesofrontal DA system in primates, and suggest that this projection should no longer be viewed as a unitary midline system.}, Author = {Williams, S. M. and Goldman-Rakic, P. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Frontal Lobe;Mesencephalon;Magnetic Resonance Imaging;Macaca mulatta;Fluorescent Dyes;Brain Mapping;Synaptic Transmission;Animals;Dopamine;24 Pubmed search results 2008;Neurons;Amidines}, Medline = {98313149}, Month = {6}, Nlm_Id = {9110718}, Number = {4}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.}, Pages = {321-45}, Pubmed = {9651129}, Title = {Widespread origin of the primate mesofrontal dopamine system}, Uuid = {992614A9-EADC-4B3C-9F94-3F5BD0754439}, Volume = {8}, Year = {1998}} @article{Williams:2005b, Abstract = {Regressive events that refine exuberant or inaccurate connections are critical in neuronal development. We used multi-photon, time-lapse imaging to examine how dendrites of Drosophila dendritic arborizing (da) sensory neurons are eliminated during early metamorphosis, and how intrinsic and extrinsic cellular mechanisms control this deconstruction. Removal of the larval dendritic arbor involves two mechanisms: local degeneration and branch retraction. In local degeneration, major branch severing events entail focal disruption of the microtubule cytoskeleton, followed by thinning of the disrupted region, severing and fragmentation. Retraction was observed at distal tips of branches and in proximal stumps after severing events. The pruning program of da neuron dendrites is steroid induced; cell-autonomous dominant-negative inhibition of steroid action blocks local degeneration, although retraction events still occur. Our data suggest that steroid-induced changes in the epidermis may contribute to dendritic retraction. Finally, we find that phagocytic blood cells not only engulf neuronal debris but also attack and sever intact branches that show signs of destabilization.}, Author = {Williams, Darren W. and Truman, James W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Cytoskeleton;Dendrites;Receptors, Steroid;Phagocytes;Research Support, U.S. Gov't, P.H.S.;Abdomen;Microscopy, Video;Drosophila melanogaster;Research Support, N.I.H., Extramural;Metamorphosis, Biological;Fluorescent Dyes;Neurons, Afferent;Animals;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8701744}, Number = {16}, Organization = {Department of Biology, University of Washington, Seattle, WA 98195, USA. dww\@u.washington.edu}, Pages = {3631-42}, Pii = {dev.01928}, Pubmed = {16033801}, Title = {Cellular mechanisms of dendrite pruning in Drosophila: insights from in vivo time-lapse of remodeling dendritic arborizing sensory neurons}, Uuid = {650F9964-00AB-11DB-9E68-000D9346EC2A}, Volume = {132}, Year = {2005}, url = {papers/Williams_Development2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.01928}} @article{Williams:2001, Abstract = {Perivascular cells are a heterogeneous population found in the central nervous system (CNS) and the peripheral nervous system (PNS). Several terms are used for these cells, including perivascular cells, perivascular macrophages, perivascular microglia, fluorescent granular perithelial cells (FGP), or Mato cells. Different terminology used may reflect subpopulations of perivascular cells within different anatomic regions and experimental paradigms, neuropathological conditions, and species studied. Different terminology also points to the lack of clear consensus of what cells are perivascular cells in different disease states and models, especially with breakdown of the blood-brain barrier (BBB). Despite this, there is consensus that perivascular cells, although a minor component of the CNS, are important immunoregulatory cells. Perivascular cells are bone marrow derived, continuously turn over in the CNS, and are found adjacent to CNS vessels. Thus, they are potential sensors of CNS and peripheral immune system perturbations; are activated in models of CNS inflammation, autoimmune disease, neuronal injury and death; and are implicated as phagocytic and pinocytotic cells in models of stroke and hypertension. Recent evidence from our laboratory implicate perivascular cells as primary targets of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection in the CNS of humans and macaques. This article reviews current knowledge of perivascular cells, including anatomic location and nomenclature and putative immunoregulatory roles, and discusses new data on the infection of these cells by SIV, their accumulation after SIV infection, and a possible role of the immune system in SIV encephalitis.}, Author = {Williams, K. and Alvarez, X. and Lackner, A. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Research Support, Non-U.S. Gov't;Central Nervous System;Nerve Degeneration;Bone Marrow Cells;AIDS Dementia Complex;Immunologic Surveillance;Research Support, U.S. Gov't, P.H.S.;11 Glia;Microglia;review, tutorial;Blood Vessels;Macrophages;Humans;Animals;Immune System;review}, Medline = {21479411}, Month = {11}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Medicine, Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. kenneth\_williams\@hms.harvard.edu}, Pages = {156-64}, Pii = {10.1002/glia.1105}, Pubmed = {11596124}, Title = {Central nervous system perivascular cells are immunoregulatory cells that connect the CNS with the peripheral immune system}, Uuid = {5D113672-C206-45F0-9FB3-1B2349459B9D}, Volume = {36}, Year = {2001}, url = {papers/Williams_Glia2001.pdf}} @article{Williams:2005a, Abstract = {The genesis of dendritic shape during development sets in place key characteristics of a neuron's physiology and connectivity. During this construction, a cell interprets intrinsic cell-specific developmental programs and cues from the environment to generate its final phenotype. In insects that undergo complete metamorphosis certain neurons function in the larval nervous system and then remodel to generate an adult-specific arbor. By studying the dendrites of neurons that undergo such a cellular metamorphosis, one can explore the mechanisms that underlie both stereotyped pruning and local remodeling. Live imaging techniques in intact Drosophila have been especially useful in examining the outgrowth of the adult-specific dendritic arbors in remodeling dendritic arborizing (da) sensory neurons. These neurons show an initial scaffold-building phase during which the cell establishes the overall shape of the arbor and then switch to an elaboration phase where the arbor is filled out with higher order branches. The cellular machinery employed during these two phases is different, with branch retraction being a prominent feature of the scaffold building phase but absent from the elaboration phase. The transition between these two modes does not appear to be "hard-wired" but is plastic and under the extrinsic control of developmental hormones. This transition in branch dynamics may also involve changes in calcium signaling in the growing arbor. The potential relationship between hormone-induced transcriptional change and the calcium dynamics in dendritic morphogenesis is discussed.}, Author = {Williams, D. W. and Truman, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0022-3034}, Journal = {J Neurobiol}, Keywords = {Dendrites;Insects;Research Support, U.S. Gov't, P.H.S.;Time Factors;Research Support, N.I.H., Extramural;Metamorphosis, Biological;Nervous System;Hormones;Animals;24 Pubmed search results 2008;review;Neurons}, Month = {7}, Nlm_Id = {0213640}, Number = {1}, Organization = {Department of Biology, University of Washington, Seattle, Washington 98195, USA.}, Pages = {24-33}, Pubmed = {15884009}, Title = {Remodeling dendrites during insect metamorphosis}, Uuid = {689B59D5-F466-4BED-AF06-D27CD81960F8}, Volume = {64}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/neu.20151}} @article{Williams:1992, Abstract = {We have compared phenotypic and functional properties of surgically derived adult human microglia to autologous and allogenic peripheral blood-derived monocytes and to astrocytes derived from the same surgical resection. We found that microglia differed from peripheral blood monocytes with respect to adhesion properties and survival rates in vitro. Microglia, similar to resident macrophages in different tissues, expressed many but not all (CD4, Leu-M3, non-specific esterase) monocyte/macrophage associated markers tested, a pattern similar to that of terminally differentiated cells of this lineage. As with other human tissue macrophages, but in contrast to astrocytes, microglia did not undergo DNA synthesis in vitro, assessed using BrdU incorporation. Under basal culture conditions the majority of microglia of all morphologic subtypes (ameboid, bipolar, ramified) expressed MHC class II molecules; by flow cytometric analysis, mean fluorescence intensity of these cells was less than that of blood monocytes (relative to isotype control). In vitro MHC class II antigen expression on microglia, under basal and interferon gamma activating conditions, was greater than on astrocytes. Freshly derived T cells cultured with 1-10\%autologous microglia plus Candida albicans underwent active proliferation, indicating the functional capacity of the microglia to serve as antigen-presenting cells.}, Author = {Williams, K. and Bar-Or, A. and Ulvestad, E. and Olivier, A. and Antel, J. P. and Yong, V. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Monocytes;Research Support, Non-U.S. Gov't;Neuroglia;Phenotype;Histocompatibility Antigens Class II;Astrocytes;Comparative Study;Cell Division;Cell Survival;11 Glia;Humans;Cells, Cultured;Major Histocompatibility Complex}, Medline = {92388944}, Month = {9}, Nlm_Id = {2985192R}, Number = {5}, Organization = {Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Quebec, Canada.}, Pages = {538-49}, Pubmed = {1517774}, Title = {Biology of adult human microglia in culture: comparisons with peripheral blood monocytes and astrocytes}, Uuid = {490AFE1B-1B85-4380-85BA-8DCB1AFFA090}, Volume = {51}, Year = {1992}} @article{Williams:2004, Abstract = {In vivo time-lapse multiphoton microscopy was used to analyze the remodeling of the dendritic arborizing (da) sensory neuron known as dorsal dendritic arborizing neuron E (ddaE) during metamorphosis. After its larval processes have been removed, the cell body of ddaE repositions itself on the body wall between 25 and 40 hr after puparium formation (APF) and begins its adult outgrowth at 40 hr APF. The scaffold of the arbor is laid down between 40 and 54 hr APF, when growth is characterized by high filopodial activity at both terminal and interstitial positions and by branch retraction along with branch establishment. Later in development, filopodial activity remains high but is confined to terminal branches, and branch retraction is no longer seen. Treatment with the insect hormone juvenile hormone (JH), a key regulator of metamorphosis, alters the shape and complexity of the adult dendritic tree in a time-dependent manner. Early treatments with juvenile hormone mimic (JHm) appear to repress extension programs and maintain retraction programs. With later JHm treatments, extension programs appear normal, but retraction programs are maintained beyond their normal time. The JH treatments show the importance of retraction programs in establishing the overall arbor shape.}, Author = {Williams, Darren W. and Truman, James W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Pupa;Dendrites;Cell Differentiation;Juvenile Hormones;Larva;Research Support, U.S. Gov't, P.H.S.;Pyridines;Time Factors;Animals, Genetically Modified;Drosophila;Metamorphosis, Biological;Microscopy, Fluorescence, Multiphoton;Neurons, Afferent;Genes, Reporter;Animals;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {8102140}, Number = {7}, Organization = {Department of Biology, University of Washington, Seattle, Washington 98195-1800, USA. dww\@u.washington.edu}, Pages = {1541-50}, Pii = {24/7/1541}, Pubmed = {14973231}, Title = {Mechanisms of dendritic elaboration of sensory neurons in Drosophila: insights from in vivo time lapse}, Uuid = {6CA69234-AF45-42DE-BE44-1801785C662F}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4521-03.2004}} @article{Williams:2005, Author = {Williams, Bryan R. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1087-0156}, Journal = {Nat Biotechnol}, Keywords = {23 RNAi;23 Technique}, Month = {2}, Nlm_Id = {9604648}, Number = {2}, Organization = {Bryan R.G. Williams is at the Cleveland Clinic Foundation, Department of Cancer Biology, NB40 The Lerner Research Institute, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA. williab\@ccf.org.}, Pages = {181-2}, Pii = {nbt0205-181}, Pubmed = {15696144}, Title = {Dicing with siRNA}, Uuid = {C9FCF7D6-CA59-421C-B56F-A55F911A57C9}, Volume = {23}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nbt0205-181}} @article{Williams:2006, Abstract = {Pruning is important for sculpting neural circuits, as it removes excessive or inaccurate projections. Here we show that the removal of sensory neuron dendrites during pruning in Drosophila melanogaster is directed by local caspase activity. Suppressing caspase activity prevented dendrite removal, whereas a global activation of caspases within a neuron caused cell death. A new genetically encoded caspase probe revealed that caspase activity is confined to the degenerating dendrites of pruning neurons.}, Author = {Williams, Darren W. and Kondo, Shu and Krzyzanowska, Agnieszka and Hiromi, Yasushi and Truman, James W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {research support, n.i.h., extramural ;Animals;Enzyme Activation;Ganglia, Spinal;Enzyme Inhibitors;Fluorescent Antibody Technique;Apoptosis;Neurons, Afferent;Animals, Genetically Modified;comparative study ;Caspases;Time Factors;Dendrites;research support, non-u.s. gov't ;Analysis of Variance;Drosophila melanogaster;24 Pubmed search results 2008;Drosophila Proteins}, Month = {10}, Nlm_Id = {9809671}, Number = {10}, Organization = {MRC Centre for Developmental Neurobiology, King's College London, London SE1 1UL, UK. darren.williams\@kcl.ac.uk}, Pages = {1234-6}, Pii = {nn1774}, Pubmed = {16980964}, Title = {Local caspase activity directs engulfment of dendrites during pruning}, Uuid = {BAF58864-F066-4756-AF20-1930886FEB55}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1774}} @article{Williams:1997, Abstract = {When exposed to platelet-derived growth factor (PDGF), uncommitted neuroepithelial cells from the developing cortex of embryonic day 14 (E14) rats develop into neurons. Outward signs of the neuronal phenotype are not observed for 4 days following exposure to PDGF. However, only a brief (2-3 hr) period of PDGF receptor activation is required to initiate neuronal development. During the window of receptor activation, RNA synthesis is essential, but protein synthesis is not. These observations indicate that specification of neuronal fate is mediated by an immediate early gene response. 0896-6273 Journal Article}, Author = {Williams, B. P. and Park, J. K. and Alberta, J. A. and Muhlebach, S. G. and Hwang, G. Y. and Roberts, T. M. and Stiles, C. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {RNA/biosynthesis;Cell Differentiation;Gene Expression/*drug effects;Rats;Neurons/*cytology/drug effects;Cerebral Cortex/cytology/metabolism;Cerebral Ventricles/*cytology;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Platelet-Derived Growth Factor/metabolism/*pharmacology;Animals;Support, Non-U.S. Gov't;*Genes, Immediate-Early;C abstr;Stem Cells/*cytology}, Number = {4}, Organization = {Department of Microbiology and Molecular Genetics, Harvard Medical School and the Dana Farber Cancer Institute, Boston, Massachusetts 02115, USA.}, Pages = {553-62}, Pubmed = {9136765}, Title = {A PDGF-regulated immediate early gene response initiates neuronal differentiation in ventricular zone progenitor cells}, Uuid = {DB9296BE-91D0-4B59-9430-2588A81C5A40}, Volume = {18}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9136765}} @article{Williams:2007, Abstract = {Synapses are located throughout the often-elaborate dendritic tree of central neurons. Hebbian models of plasticity require temporal association between synaptic input and neuronal output to produce long-term potentiation of excitatory transmission. Recent studies have highlighted how active dendritic spiking mechanisms control this association. Here, we review new work showing that associative synaptic plasticity can be generated without neuronal output and that the interplay between neuronal architecture and the active electrical properties of the dendritic tree regulates synaptic plasticity.}, Author = {Williams, Stephen R. and Wozny, Christian and Mitchell, Simon J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {24 Pubmed search results 2008}, Month = {12}, Nlm_Id = {8809320}, Number = {6}, Organization = {MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK.}, Pages = {947-53}, Pii = {S0896-6273(07)00969-5}, Pubmed = {18093518}, Title = {The back and forth of dendritic plasticity}, Uuid = {7D033EF4-E1F2-4B9B-9AFA-8974AE33EE20}, Volume = {56}, Year = {2007}, url = {papers/Williams_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.12.004}} @article{Williams:1991, Abstract = {The role of edema in the pathogenesis of hypoxic-ischemic injury in the immature brain is controversial. We studied 15 chronically instrumented fetal sheep following transient cerebral ischemia, to estimate changes in extracellular space using an impedance technique, to quantify the electroencephalogram with real-time spectral analysis, and to assess histologic outcome 3 days after the insult. These measurements were made in the parasagittal cortex. There was a rapid loss of extracellular space from 5 +/- 2 minutes after the onset of ischemia. Following 10 minutes of ischemia (n = 7) the intracellular edema peaked but then quickly resolved (6 +/- 4 minutes), and mild selective neuronal loss was seen. In contrast, the swelling was biphasic after 30-40 minutes of ischemia (n = 8). The early edema resolved slowly (28 +/- 12 minutes) but incompletely, and secondary swelling began at 7 +/- 2 hours and peaked at 28 +/- 6 hours. The early swelling was the more severe. Postinsult epileptiform activity began at 8 +/- 2 hours and peaked at 10 +/- 3 hours; later there was laminar necrosis of the underlying cortex. The secondary decrease of extracellular space indicates that a progressive loss of membrane function started with the onset of postischemic epileptiform activity. The increased metabolic load of the epileptiform activity may have worsened this delayed deterioration.}, Author = {Williams, C. E. and Gunn, A. and Gluckman, P. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0039-2499}, Journal = {Stroke}, Keywords = {Epilepsy;Electroencephalography;Research Support, Non-U.S. Gov't;21 Neurophysiology;Female;Brain Edema;Sheep;Pregnancy;Animals;Brain;24 Pubmed search results 2008;Ischemic Attack, Transient;21 Epilepsy}, Medline = {91220353}, Month = {4}, Nlm_Id = {0235266}, Number = {4}, Organization = {Department of Paediatrics, University of Auckland, New Zealand.}, Pages = {516-21}, Pubmed = {2024281}, Title = {Time course of intracellular edema and epileptiform activity following prenatal cerebral ischemia in sheep}, Uuid = {C77742F3-EB39-4610-8D9F-AAB45B06C930}, Volume = {22}, Year = {1991}} @article{Wilson:2004a, Abstract = {The tremendous complexity of the adult forebrain makes it a challenging task to elucidate how this structure forms during embryonic development. Nevertheless, we are beginning to understand how a simple epithelial sheet of ectoderm gives rise to the labyrinthine network of cells that constitutes the functional forebrain. Here, we discuss early events in forebrain development-those that lead to the establishment of the anterior neural plate and the regional subdivision of this territory into the different domains of the prospective forebrain. 1534-5807 Journal Article}, Author = {Wilson, S. W. and Houart, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Dev Cell}, Keywords = {F abstr;10 Development}, Number = {2}, Organization = {Department of Anatomy and Developmental Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom.}, Pages = {167-81}, Pubmed = {14960272}, Title = {Early steps in the development of the forebrain}, Uuid = {5FFF03CB-D9FF-4830-920C-449A5DEFA9F7}, Volume = {6}, Year = {2004}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14960272}} @article{Wilson:2005, Abstract = {Drosophila olfactory receptor neurons project to the antennal lobe, the insect analog of the mammalian olfactory bulb. GABAergic synaptic inhibition is thought to play a critical role in olfactory processing in the antennal lobe and olfactory bulb. However, the properties of GABAergic neurons and the cellular effects of GABA have not been described in Drosophila, an important model organism for olfaction research. We have used whole-cell patch-clamp recording, pharmacology, immunohistochemistry, and genetic markers to investigate how GABAergic inhibition affects olfactory processing in the Drosophila antennal lobe. We show that many axonless local neurons (LNs) in the adult antennal lobe are GABAergic. GABA hyperpolarizes antennal lobe projection neurons (PNs) via two distinct conductances, blocked by a GABAA- and GABAB-type antagonist, respectively. Whereas GABAA receptors shape PN odor responses during the early phase of odor responses, GABAB receptors mediate odor-evoked inhibition on longer time scales. The patterns of odor-evoked GABAB-mediated inhibition differ across glomeruli and across odors. Finally, we show that LNs display broad but diverse morphologies and odor preferences, suggesting a cellular basis for odor- and glomerulus-dependent patterns of inhibition. Together, these results are consistent with a model in which odors elicit stimulus-specific spatial patterns of GABA release, and as a result, GABAergic inhibition increases the degree of difference between the neural representations of different odors.}, Author = {Wilson, Rachel I. and Laurent, Gilles}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {gamma-Aminobutyric Acid;research support, n.i.h., extramural ;Animals;Olfactory Receptor Neurons;research support, u.s. gov't, p.h.s. ;research support, u.s. gov't, non-p.h.s. ;Synaptic Transmission;Cell Count;Animals, Genetically Modified;Patch-Clamp Techniques;comparative study ;Recombinant Fusion Proteins;Green Fluorescent Proteins;Odors;research support, non-u.s. gov't ;Olfactory Bulb;21 Neurophysiology;Antigens, CD8;Fushi Tarazu Transcription Factors;Drosophila;Membrane Potentials;Organophosphorus Compounds;Sense Organs;Immunohistochemistry;24 Pubmed search results 2008;Neural Inhibition;Drosophila Proteins}, Month = {10}, Nlm_Id = {8102140}, Number = {40}, Organization = {Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA. rachel\_wilson\@hms.harvard.edu}, Pages = {9069-79}, Pii = {25/40/9069}, Pubmed = {16207866}, Title = {Role of GABAergic inhibition in shaping odor-evoked spatiotemporal patterns in the Drosophila antennal lobe}, Uuid = {EA79EEF0-0291-44EA-9FCB-1CA0DEA9B603}, Volume = {25}, Year = {2005}, url = {papers/Wilson_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2070-05.2005}} @article{Wilson:2007, Author = {Wilson, Rachel I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Behavior, Animal;21 Neurophysiology;Drosophila Proteins;Drosophila melanogaster;Anopheles gambiae;comment;Neurons, Afferent;Animals;Humans;Carbon Dioxide;24 Pubmed search results 2008;news}, Month = {1}, Nlm_Id = {0410462}, Number = {7123}, Pages = {30-1}, Pii = {445030a}, Pubmed = {17203047}, Title = {Neurobiology: scent secrets of insects}, Uuid = {4174C4F3-BA97-4B9A-AABF-C6260ED111A7}, Volume = {445}, Year = {2007}, url = {papers/Wilson_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/445030a}} @article{Wilson:2004, Abstract = {Molecular genetics has revealed a precise stereotypy in the projection of primary olfactory sensory neurons onto secondary neurons. A major challenge is to understand how this mapping translates into odor responses in these second-order neurons. We investigated this question in Drosophila using whole-cell recordings in vivo. We observe that monomolecular odors generally elicit responses in large ensembles of antennal lobe neurons. Comparison of odor-evoked activity from afferents and postsynaptic neurons in the same glomerulus revealed that second-order neurons display broader tuning and more complex responses than their primary afferents. This indicates a major transformation of odor representations, implicating lateral interactions within the antennal lobe.}, Author = {Wilson, Rachel I. and Turner, Glenn C. and Laurent, Gilles}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Animals;Synapses;Olfactory Receptor Neurons;Patch-Clamp Techniques;Neurons, Afferent;research support, non-u.s. gov't;Odors;Smell;Receptors, GABA-A;Action Potentials;Olfactory Pathways;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Picrotoxin;Nervous System Physiology;Drosophila;GABA Antagonists;Sense Organs;24 Pubmed search results 2008;Neural Inhibition;research support, u.s. gov't, non-p.h.s.;Excitatory Postsynaptic Potentials}, Month = {1}, Nlm_Id = {0404511}, Number = {5656}, Organization = {Division of Biology, 139-74, California Institute of Technology, Pasadena, CA 91125, USA.}, Pages = {366-70}, Pii = {1090782}, Pubmed = {14684826}, Title = {Transformation of olfactory representations in the Drosophila antennal lobe}, Uuid = {1FEF8179-D150-47BB-90D3-62E91EF88E04}, Volume = {303}, Year = {2004}, url = {papers/Wilson_Science2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1090782}} @article{Wines-Samuelson:2005, Abstract = {Presenilin-1 (PS1), the major causative gene of familial Alzheimer disease, regulates neuronal differentiation and Notch signaling during early neural development. To investigate the role of PS1 in neuronal migration and cortical lamination of the postnatal brain, we circumvented the perinatal lethality of PS1-null mice by generating a conditional knockout (cKO) mouse in which PS1 inactivation is restricted to neural progenitor cells (NPCs) and NPC-derived neurons and glia. BrdU birthdating analysis revealed that many late-born neurons fail to migrate beyond the early-born neurons to arrive at their appropriate positions in the superficial layer, while the migration of the early-born neurons is largely normal. The migration defect of late-born neurons coincides with the progressive reduction of radial glia in PS1 cKO mice. In contrast to the premature loss of Cajal-Retzius (CR) neurons in PS1-null mice, generation and survival of CR neurons are unaffected in PS1 cKO mice. Furthermore, the number of proliferating meningeal cells, which have been shown to be important for the survival of CR neurons, is increased in PS1-null mice but not in PS1 cKO mice. These findings show a cell-autonomous role for PS1 in cortical lamination and radial glial development, and a non-cell-autonomous role for PS1 in CR neuron survival.}, Author = {Wines-Samuelson, Mary and Handler, Melissa and Shen, Jie}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {10 Development}, Month = {1}, Nlm_Id = {0372762}, Number = {2}, Organization = {Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States.}, Pages = {332-46}, Pii = {S0012-1606(04)00661-X}, Pubmed = {15617678}, Title = {Role of presenilin-1 in cortical lamination and survival of Cajal-Retzius neurons}, Uuid = {49AAB3DB-3790-46AC-B9D6-6C04FE2F3B82}, Volume = {277}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2004.09.024}} @article{Winner:2002, Abstract = {In the adult rat olfactory bulb, neurons are continually generated from progenitors that reside in the lateral ventricle wall. This study investigates long-term survival and cell death of newly generated cells within the adult olfactory bulb. After injecting rats at 2 months of age with 5-bromodeoxyuridine (BrdU), the newly generated cells were quantified over a period of 19 months. A peak of BrdU-positive cells was reached in the olfactory bulb 1 month after BrdU injection, when all new cells have finished migrating from the ventricle wall. Thereafter, a reduction of BrdU-positive cells to about 50\%was observed and it was confirmed by dUTP-nick end-labelling (TUNEL) that progenitors and young neurons undergo programmed cell death. However, cells that survived the first 3 months after BrdU injection persisted for up to 19 months. The majority of the BrdU-positive cells that reach the olfactory bulb differentiate into granule cells, but a small fraction migrate further into the glomerular layer. These newborn cells differentiate more slowly into periglomerular interneurons, with a delay of more than 1 month when compared to the granule cells. The newly generated periglomerular neurons, among them a significant fraction of dopaminergic cells, showed a similar decline in number compared to the granule cell layer and long-term survival for the remaining new neurons of up to 19 months. Rather than replacing old neurons, this data suggests that adult olfactory bulb neurogenesis utilizes the overproduction and turnover of young neurons, which is reminiscent of the cellular dynamics observed during brain development. 22318906 0953-816x Journal Article}, Author = {Winner, B. and Cooper-Kuhn, C. M. and Aigner, R. and Winkler, J. and Kuhn, H. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Cell Survival;Cell Differentiation;Animals;Rats;Apoptosis;Female;B pdf;02 Adult neurogenesis migration;Rats, Wistar;Time Factors;Olfactory Bulb;In Situ Nick-End Labeling;Neurons;Cell Division;Immunohistochemistry;Stem Cells;Bromodeoxyuridine;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {22318906}, Month = {11}, Nlm_Id = {8918110}, Number = {9}, Organization = {Department of Neurology, University of Regensburg, Universitatsstrasse 84, D- 93053 Regensburg, Germany Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.}, Pages = {1681-9}, Pii = {2238}, Pubmed = {12431220}, Title = {Long-term survival and cell death of newly generated neurons in the adult rat olfactory bulb}, Uuid = {27275CB2-7C2B-404F-B4C6-F79E07D98A87}, Volume = {16}, Year = {2002}, url = {papers/Winner_EurJNeurosci2002.pdf}} @article{Winship:2008, Abstract = {Functional mapping and microstimulation studies suggest that recovery after stroke damage can be attributed to surviving brain regions taking on the functional roles of lost tissues. Although this model is well supported by data, it is not clear how activity in single neurons is altered in relation to cortical functional maps. It is conceivable that individual surviving neurons could adopt new roles at the expense of their usual function. Alternatively, neurons that contribute to recovery may take on multiple functions and exhibit a wider repertoire of neuronal processing. In vivo two-photon calcium imaging was used in adult mice within reorganized forelimb and hindlimb somatosensory functional maps to determine how the response properties of individual neurons and glia were altered during recovery from ischemic damage over a period of 2-8 weeks. Single-cell calcium imaging revealed that the limb selectivity of individual neurons was altered during recovery from ischemia, such that neurons normally selective for a single contralateral limb processed information from multiple limbs. Altered limb selectivity was most prominent in border regions between stroke-altered forelimb and hindlimb macroscopic map representations, and peaked 1 month after the targeted insult. Two months after stroke, individual neurons near the center of reorganized functional areas became more selective for a preferred limb. These previously unreported forms of plasticity indicate that in adult animals, seemingly hardwired cortical neurons first adopt wider functional roles as they develop strategies to compensate for loss of specific sensory modalities after forms of brain damage such as stroke.}, Author = {Winship, Ian R. and Murphy, Timothy H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Optics;Calcium Signaling;Photic Stimulation;Animals;Recovery of Function;Neuronal Plasticity;Afferent Pathways;Functional Laterality;Neurons, Afferent;Staining and Labeling;Mice, Inbred C57BL;research support, non-u.s. gov't;Male;Nerve Regeneration;Stroke;Adaptation, Physiological;Neurons;Brain Ischemia;Extremities;Somatosensory Cortex;Mice;24 Pubmed search results 2008;Brain Mapping}, Month = {6}, Nlm_Id = {8102140}, Number = {26}, Organization = {Department of Psychiatry, Brain Research Centre, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.}, Pages = {6592-606}, Pii = {28/26/6592}, Pubmed = {18579732}, Title = {In vivo calcium imaging reveals functional rewiring of single somatosensory neurons after stroke}, Uuid = {4E4EFA22-1601-476A-8CBB-62260A35A732}, Volume = {28}, Year = {2008}, url = {papers/Winship_JNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0622-08.2008}} @article{Winter:1995, Abstract = {Within the central nervous system (CNS) ciliary neurotrophic factor (CNTF) is expressed by astrocytes where it remains stored as an intracellular protein; its release and function as an extracellular ligand are thought to occur in the event of cellular injury. We find that overexpression of CNTF in transgenic mice recapitulates the glial response to CNS lesion, as does its injection into the uninjured brain. These results demonstrate that CNTF functions as an inducer of reactive gliosis, a condition associated with a number of neurological diseases of the CNS. 95320176 0027-8424 Journal Article}, Author = {Winter, C. G. and Saotome, Y. and Levison, S. W. and Hirsh, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {*Nerve Degeneration/drug effects;Human;Ciliary Neurotrophic Factor;Rats;Glial Fibrillary Acidic Protein/analysis/biosynthesis;Macrophage-1 Antigen/analysis;Animal;Mice, Transgenic;G abstr;11 Glia;Neurons, Afferent/metabolism/pathology;Gliosis/chemically induced/pathology/*physiopathology;Support, Non-U.S. Gov't;Astrocytes/*physiology;Nerve Tissue Proteins/analysis/*biosynthesis/*pharmacology;DNA, Complementary;Mice;Gene Expression;Recombinant Proteins/pharmacology;Nerve Growth Factors/biosynthesis/pharmacology;Olfactory Bulb/metabolism/pathology}, Number = {13}, Organization = {Department of Biochemistry and Molecular Biophysics, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.}, Pages = {5865-9}, Pubmed = {7597043}, Title = {A role for ciliary neurotrophic factor as an inducer of reactive gliosis, the glial response to central nervous system injury}, Uuid = {B7469FB2-E4C2-4334-B8AB-3AD5A30F28D2}, Volume = {92}, Year = {1995}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7597043}} @article{Witting:2000, Abstract = {Microglia, the tissue macrophages of the brain, play a crucial role in recognition and phagocytic removal of apoptotic neurons. The microglial receptors for recognition of apoptotic neurons are not yet characterized. Here we established a co-culture model of primary microglia and cerebellar granule neurons to examine the receptor systems involved in recognition/uptake of apoptotic neurons. Treatment with 100 microM S-nitrosocysteine induced apoptosis of cerebellar neurons as indicated by nuclear condensation and phosphatidylserine exposure to the exoplasmic leaflet of the plasma membrane. Microglial cells were added to neurons 2 h after apoptosis induction and co-cultured for 6 h in the presence of ligands that inhibit recognition by binding to respective receptors. Binding/phagocytosis was determined after combined 4', 6-diamidino-2-phenylindole/propidium iodide (for apoptotic/necrotic neurons) and lectin staining (for microglia). Uptake of apoptotic neurons was reduced by N-acetylglucosamine or galactose, suggesting that recognition involves asialoglycoprotein-like lectins. Furthermore, the inhibition of microglial binding/uptake of apoptotic neurons by RGDS peptide suggests a role of microglial vitronectin receptor. As microglia selectively bind lipid vesicles enriched in phosphatidylserine and O-phospho-L-serine interfered with the uptake of apoptotic neurons, an involvement of phosphatidylserine receptor is rather likely. Apoptotic neurons do not release soluble signals that serve to attract or activate microglia. Collectively, these results suggest that apoptotic neurons generate a complex surface signal recognized by different receptor systems on microglia.}, Author = {Witting, A. and M{\"u}ller, P. and Herrmann, A. and Kettenmann, H. and Nolte, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0022-3042}, Journal = {J Neurochem}, Keywords = {Microscopy, Video;Phagocytosis;Animals;Cells, Cultured;Nitroso Compounds;Rats;Integrins;Macrophages;Receptors, Vitronectin;S-Nitrosothiols;Apoptosis;Microglia;Phosphatidylserines;Chemotaxis;Rats, Wistar;11 Glia;Cysteine;Support, Non-U.S. Gov't;Animals, Newborn;Coculture;Cerebral Cortex;Neurons;Cerebellum;Necrosis;Lectins}, Medline = {20396180}, Month = {9}, Nlm_Id = {2985190R}, Number = {3}, Organization = {Max Delbr{\"u}ck Center for Molecular Medicine, Cellular Neurosciences, Berlin, Germany.}, Pages = {1060-70}, Pubmed = {10936187}, Title = {Phagocytic clearance of apoptotic neurons by Microglia/Brain macrophages in vitro: involvement of lectin-, integrin-, and phosphatidylserine-mediated recognition}, Uuid = {D3E13CC3-8DFE-4D64-8B81-BE1EBCE6C539}, Volume = {75}, Year = {2000}, url = {papers/Witting_JNeurochem2000.pdf}} @article{Wolf:2002, Abstract = {This study analyzes how the antigen specificity, the subtype, and the activation state of T cells modulate their recently discovered neuroprotective potential. We assessed the prevention from neuronal damage in organotypic entorhinal-hippocampal slice cultures after co-culture with Th1 and Th2 cells either specific for myelin basic protein (MBP) or ovalbumin (OVA). We found that MBP-specific Th2 cells were the most effective in preventing central nervous system (CNS) tissue from secondary injury. This neuroprotective T cell effect appears to be mediated by soluble factors. After stimulation with phorbol myristate acetate and ionomycin, all T cells were most effective in preventing neuronal death. Our data show that the T cell subtype and activation state are important features in determining the neuroprotective potential of these cells.}, Author = {Wolf, Susanne A. and Fisher, Jasmin and Bechmann, Ingo and Steiner, Barbara and Kwidzinski, Erik and Nitsch, Robert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0165-5728}, Journal = {J Neuroimmunol}, Keywords = {Mice, Inbred BALB C;Cell Survival;Contact Inhibition;Nerve Degeneration;Animals;Th2 Cells;Ovalbumin;Cytokines;Myelin Basic Proteins;Brain;11 Glia;Chemotaxis, Leukocyte;Brain Injuries;Animals, Newborn;Tetradecanoylphorbol Acetate;Neurons;Th1 Cells;Epitopes;Mice;Research Support, Non-U.S. Gov't}, Medline = {22336842}, Month = {12}, Nlm_Id = {8109498}, Number = {1-2}, Organization = {Department of Cell and Neurobiology, Institute of Anatomy, Humboldt-University Hospital Charit\`{e}, 10098, Berlin, Germany.}, Pages = {72-80}, Pii = {S0165572802003673}, Pubmed = {12446010}, Title = {Neuroprotection by T-cells depends on their subtype and activation state}, Uuid = {4B4E657A-0EC4-4056-BE35-1B9B26137914}, Volume = {133}, Year = {2002}} @article{Wolf-Jurewicz:1982, Abstract = {Following destructions of the prefrontal medial brain area in dogs two basis changes were noticed: an increase in food intake (14 dogs--group I) and a decrease of food intake (16 dogs--group II). On the basis of a histological analysis one can conclude that the differences in size, site and depth of the lesions are responsible for the obtained results. The deep lesions involving the white and grey matter in FPG area between the III and V (Kreiner's atlas) frontal planes brought about the most pronounced increase in food intake. The lesions involving only the cortex or very broad lesions in the whole prefrontal medial area and also anterior lesions between the I and III frontal planes, or posterior lesions from the VI to VIII frontal planes decreased the food intake or caused no changes in it.}, Author = {Wolf-Jurewicz, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0044-6033}, Journal = {Acta Physiol Pol}, Keywords = {Eating;Hyperphagia;Eating Disorders;Dogs;Animals;Humans;24 Pubmed search results 2008;Frontal Lobe}, Medline = {83252335}, Nlm_Id = {2985166R}, Number = {4}, Pages = {393-401}, Pubmed = {6964027}, Title = {The role of the medial prefrontal cortex in food intake in dogs}, Uuid = {589EFF10-14A3-48F2-898D-C07A4AE8EFAC}, Volume = {33}, Year = {1982}} @article{Won:2003, Abstract = {In this study, we examined the effect of the s.c. administration of (+/-) 3,4-methylenedioxymethamphetamine (MDMA) or saline on locomotor activity and Fos expression following the bilateral destruction of hippocampal dentate granule cells by colchicine in rats. The lesioned animals, when administered s.c. saline, showed a significantly greater increase in locomotor activity compared to the intact animals, and revealed a marginally significant level of increased locomotor activity compared to the sham-lesioned animals. In addition, when the lesioned animals were given s.c. saline or MDMA, there was a significant increase in Fos expression in the nucleus accumbens core, but not in the medial prefrontal cortex, dorsolateral prefrontal cortex, anterior cingulate cortex, piriform cortex, dorsal striatum, or nucleus accumbens shell, compared to the intact and sham-lesioned animals. Overall, these results suggest that the nucleus accumbens core may be involved in the enhancement of locomotor activity induced by the injection of saline alone (stress loading) or MDMA following bilateral destruction of hippocampal dentate granule cells by colchicine.}, Author = {Won, Mujun and Minabe, Yoshio and Tani, Kunihiko and Suzuki, Katsuaki and Kawai, Masayoshi and Sekine, Yoshimoto and Ashby, Charles R. and Takei, Nori and Mori, Norio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Neurons;Rats, Sprague-Dawley;07 Excitotoxicity Apoptosis;Behavior, Animal;Colchicine;Immunohistochemistry;Rats;Dentate Gyrus;Hallucinogens;06 Adult neurogenesis injury induced;Injections, Intraventricular;Animals;Male;N-Methyl-3,4-methylenedioxyamphetamine;Proto-Oncogene Proteins c-fos;Brain}, Medline = {22653025}, Month = {6}, Nlm_Id = {8500749}, Number = {2}, Organization = {Department of Psychiatry and Neurology, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan.}, Pages = {153-60}, Pii = {S0168010203000415}, Pubmed = {12767478}, Title = {The effects of dentate granule cell destruction on behavioral activity and Fos protein expression induced by systemic MDMA in rats}, Uuid = {1C698258-47AD-4483-B226-167177941838}, Volume = {46}, Year = {2003}, url = {papers/Won_NeurosciRes2003}} @article{Wong:2001, Abstract = {The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo). We report here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs). Two of the Slit-Robo GAPs (srGAPs) are expressed in regions responsive to Slit. Slit increased srGAP1- Robo1 interaction and inactivated Cdc42. A dominant negative srGAP1 blocked Slit inactivation of Cdc42 and Slit repulsion of migratory cells from the anterior subventricular zone (SVZa) of the forebrain. A constitutively active Cdc42 blocked the repulsive effect of Slit. These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization.}, Author = {Wong, K. and Ren, X. R. and Huang, Y. Z. and Xie, Y. and Liu, G. and Saito, H. and Tang, H. and Wen, L. and Brady-Kalnay, S. M. and Mei, L. and Wu, J. Y. and Xiong, W. C. and Rao, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Cell}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, 660 South Euclid Avenue, 63110, Saint Louis, MO, USA}, Pages = {209-21.}, Title = {Signal transduction in neuronal migration. roles of gtpase activating proteins and the small gtpase cdc42 in the slit-robo pathway}, Uuid = {BFD37879-2DAD-4318-91EA-23F78E0EBCBF}, Volume = {107}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11672528}} @article{Wong:2005, Abstract = {The human immunodeficiency virus type-1 (HIV-1) infects microglia, macrophages, and astrocytes in the central nervous system (CNS) and may cause severe neurological diseases, such as AIDS-related dementias or progressive encephalopathies, as a result of CNS inflammation and neurotrophin signaling defects associated with expression of viral antigens and HIV-1 replication in the brain. The HIV Tat protein can be endocytosed by surrounding uninfected cells; interacts with transcriptional coactivators/acetyltransferases, p300/CREB-binding protein, and p300/CREB-binding protein-associated factor (PCAF); and induces neuronal apoptosis. Since nerve growth factor (NGF) receptor and brain-derived neurotrophic factor receptor signaling through CREB requires p300 and PCAF histone acetyltransferases, we sought to determine whether HIV-1 Tat coactivator interactions interfere with neurotrophin receptor signaling in neuronal cells. Here, we demonstrate that Tat-coactivator interactions inhibit NGF- and brain-derived neurotrophic factor-responsive CRE trans-activation and neurotrophin protection against apoptosis in PC12 and IMR-32 neuroblastoma cells. Purified recombinant Tat or Tat-derived synthetic peptides, spanning p300- and PCAF-binding sequences, inhibit histone H3/H4 acetylation in vitro. A Tat mutant, TatK28A/K50A, defective for binding p300 and PCAF, neither repressed NGF-responsive CRE transactivation nor inhibited histone acetylation. HIV-1 Tat interacts in PCAF complexes in post-mortem CNS tissues from donor neuro-AIDS patients, as determined by fluorescence resonance energy transfer immunoconfocal microscopy. Importantly, these findings suggest that HIV-1 Tat-coactivator interactions may contribute to neurotrophin signaling impairments and neuronal apoptosis associated with HIV-1 infections of the CNS.}, Author = {Wong, Kasuen and Sharma, Anima and Awasthi, Soumya and Matlock, Elizabeth F. and Rogers, Lowery and Van Lint, Carine and Skiest, Daniel J. and Burns, Dennis K. and Harrod, Robert}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {Molecular Sequence Data;Neuroblastoma;Cell Cycle Proteins;HIV-1;Signal Transduction;Humans;Rats;Transfection;Microscopy, Confocal;Acetylation;Animals;Gene Products, tat;Transcription Factors;Cell Line, Tumor;Recombinant Fusion Proteins;PC12 Cells;11 Glia;Nerve Growth Factors;DNA-Binding Protein, Cyclic AMP-Responsive;Histones;Virus Replication;Amino Acid Sequence;Fluorescence Resonance Energy Transfer;Acetyltransferases;Pheochromocytoma;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {2985121R}, Number = {10}, Organization = {Laboratory of Molecular Virology, Department of Biological Sciences, Southern Methodist University, Dallas, Texas 75275-0376, USA.}, Pages = {9390-9}, Pii = {M408643200}, Pubmed = {15611041}, Title = {HIV-1 Tat interactions with p300 and PCAF transcriptional coactivators inhibit histone acetylation and neurotrophin signaling through CREB}, Uuid = {93049B5A-EA22-4589-8D19-6B1A1830343D}, Volume = {280}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1074/jbc.M408643200}} @article{Wood:1994, Abstract = {The use of viral vectors which infect and express genes in post-mitotic neurons is a potential strategy for the treatment of disorders affecting the central nervous system (CNS). However, the inflammatory consequences of such strategies have yet to be systematically examined. Preparations of non-replicating defective herpes simplex virus type 1 (HSV-1) amplicon vectors containing the lacZ gene were obtained by standard methods and stereotaxically injected into the adult rat dentate gyrus (DG). The consequent gene expression and inflammatory effects following microinjection were investigated. beta-Galactosidase activity was detected in neurons of the DG from 24 h to at least 12 days after vector injection. A strong inflammatory response developed within 2 days, characterized by diffuse up-regulation of major histocompatibility complex (MHC) class I antigens and the activation of microglia. After 4 days the recruitment of MHC class II+ cells, activated T lymphocytes and macrophages was detected. These features persisted for at least 31 days. Of importance was the finding of beta-galactosidase activity in a bilateral group of neurons in the supramammillary nuclei (SMN) of the posterior hypothalamus, known to send afferent projections to the DG. The onset of inflammation at this secondary site was delayed, but its cellular characteristics resembled those found at the primary site of injection. Thus, the use of preparations of defective HSV-1 vectors for gene transfer in the CNS has immunological implications both at primary and secondary sites within the CNS.(ABSTRACT TRUNCATED AT 250 WORDS)}, Author = {Wood, M. J. and Byrnes, A. P. and Pfaff, D. W. and Rabkin, S. D. and Charlton, H. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0969-7128}, Journal = {Gene Ther}, Keywords = {Gene Transfer Techniques;Encephalitis;Rats;Lac Operon;Dentate Gyrus;Time Factors;Not relevant;Defective Viruses;Gene Expression;Support, U.S. Gov't, Non-P.H.S.;11 Glia;beta-Galactosidase;Gene Therapy;Support, Non-U.S. Gov't;Herpesvirus 1, Human;Animals;Genetic Vectors}, Medline = {96050952}, Month = {9}, Nlm_Id = {9421525}, Number = {5}, Organization = {Department of Neurobiology and Behavior, Rockefeller University, New York 10021, USA.}, Pages = {283-91}, Pubmed = {7584093}, Title = {Inflammatory effects of gene transfer into the CNS with defective HSV-1 vectors}, Uuid = {B0CD275D-52CC-4301-A001-F982A0467D5D}, Volume = {1}, Year = {1994}} @article{Woodbury:2000, Abstract = {Bone marrow stromal cells exhibit multiple traits of a stem cell population. They can be greatly expanded in vitro and induced to differentiate into multiple mesenchymal cell types. However, differentiation to non-mesenchymal fates has not been demonstrated. Here, adult rat stromal cells were expanded as undifferentiated cells in culture for more than 20 passages, indicating their proliferative capacity. A simple treatment protocol induced the stromal cells to exhibit a neuronal phenotype, expressing neuron-specific enolase, NeuN, neurofilament-M, and tau. With an optimal differentiation protocol, almost 80\%of the cells expressed NSE and NF-M. The refractile cell bodies extended long processes terminating in typical growth cones and filopodia. The differentiating cells expressed nestin, characteristic of neuronal precursor stem cells, at 5 hr, but the trait was undetectable at 6 days. In contrast, expression of trkA, the nerve growth factor receptor, persisted from 5 hr through 6 days. Clonal cell lines, established from single cells, proliferated, yielding both undifferentiated and neuronal cells. Human marrow stromal cells subjected to this protocol also differentiated into neurons. Consequently, adult marrow stromal cells can be induced to overcome their mesenchymal commitment and may constitute an abundant and accessible cellular reservoir for the treatment of a variety of neurologic diseases.}, Author = {Woodbury, D. and Schwarz, E. J. and Prockop, D. J. and Black, I. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cell Differentiation;Bone Marrow;Research Support, Non-U.S. Gov't;Bone Marrow Cells;Neurofilament Proteins;08 Aberrant cell cycle;Research Support, U.S. Gov't, P.H.S.;Phosphopyruvate Hydratase;Rats;Culture Media;Mesoderm;Receptor, trkA;Cells, Cultured;Animals;Humans;Stromal Cells;Neurons}, Medline = {20392108}, Month = {8}, Nlm_Id = {7600111}, Number = {4}, Organization = {Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. woodburydl\@aol.com}, Pages = {364-70}, Pii = {10.1002/1097-4547(20000815)61:4<364::AID-JNR2>3.0.CO;2-C}, Pubmed = {10931522}, Title = {Adult rat and human bone marrow stromal cells differentiate into neurons}, Uuid = {6DCB88C3-63B3-4586-9F23-95A255031CE7}, Volume = {61}, Year = {2000}, url = {papers/Woodbury_JNeurosciRes2000.pdf}} @article{Woodbury:2002, Abstract = {Bone marrow stromal stem cells (MSCs) normally differentiate into mesenchymal derivatives but recently have also been converted into neurons, classical ectodermal cells. To begin defining underlying mechanisms, we extended our characterization of MSCs and the differentiated neurons. In addition to expected mesodermal mRNAs, populations and clonal lines of MSCs expressed germinal, endodermal, and ectodermal genes. Thus, the MSCs are apparently "multidifferentiated" in addition to being multipotent. Conversely, the differentiating neurons derived from populations and clonal lines of MSCs expressed the specific markers beta-III tubulin, tau, neurofilament-M, TOAD-64, and synaptophysin de novo. The transmitter enzymes tyrosine hydroxylase and choline acetyltransferase were localized to neuronal subpopulations. Our observations suggest that MSCs are already multidifferentiated and that neural differentiation comprises quantitative modulation of gene expression rather than simple on-off switching of neural-specific genes.}, Author = {Woodbury, Dale and Reynolds, Kathleen and Black, Ira B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Cell Differentiation;Animals;Ectoderm;Gene Expression Regulation, Developmental;Rats;Synaptic Transmission;Femur;08 Aberrant cell cycle;Bone Marrow Cells;Research Support, U.S. Gov't, P.H.S.;Mesoderm;Neuroglia;Neurons;Age Factors;Endoderm;Clone Cells;Stromal Cells;Nerve Tissue Proteins;Research Support, Non-U.S. Gov't}, Medline = {22194578}, Month = {9}, Nlm_Id = {7600111}, Number = {6}, Organization = {Department of Neuroscience and Cell Biology, UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA. woodburydl\@aol.com}, Pages = {908-17}, Pubmed = {12205683}, Title = {Adult bone marrow stromal stem cells express germline, ectodermal, endodermal, and mesodermal genes prior to neurogenesis}, Uuid = {A34674CC-5224-4842-AB57-0E400C42F424}, Volume = {69}, Year = {2002}, url = {papers/Woodbury_JNeurosciRes2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10365}} @article{Woods:2000, Abstract = {The ability of lentiviral vectors to transfer genes into human hematopoietic stem cells was studied, using a human immunodeficiency virus 1 (HIV-1)-derived vector expressing the green fluorescence protein (GFP) downstream of the phosphoglycerate kinase (PGK) promoter and pseudotyped with the G protein of vesicular stomatitis virus (VSV). High-efficiency transduction of human cord blood CD34(+) cells was achieved after overnight incubation with vector particles. Sixteen to 28 percent of individual colony-forming units granulocyte-macrophage (CFU-GM) colonies derived from cord blood CD34(+) cells were positive by polymerase chain reaction (PCR) for the GFP gene. The transduction efficiency of SCID-repopulating cells (SRC) within the cord blood CD34(+) population was assessed by serial transplantation into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. When 400,000 cord blood CD34(+) cells were transplanted into primary recipients, all primary and secondary recipients contained and expressed the transgene. Over 50\%of CFU-GM colonies derived from the bone marrow of these primary and secondary recipients contained the vector on average as determined by PCR. Transplantation of transduced cells in limiting dilution generated GFP(+) lymphoid and myeloid progeny cells that may have arisen from a single SRC. Inverse PCR analysis was used to amplify vector-chromosomal junctional fragments in colonies derived from SRC and confirmed that the vector was integrated. These results show that lentiviral vectors can efficiently transduce very primitive human hematopoietic progenitor and stem cells. (Blood. 2000;96:3725-3733)}, Author = {Woods, N. B. and Fahlman, C. and Mikkola, H. and Hamaguchi, I. and Olsson, K. and Zufferey, R. and Jacobsen, S. E. and Trono, D. and Karlsson, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Transduction, Genetic;HIV-1;Mice, Inbred NOD;Humans;Animals;Lentivirus;Mice, SCID;Antigens, CD34;11 Glia;Immunophenotyping;Hematopoietic Stem Cell Transplantation;Genetic Vectors;Hematopoiesis;Cell Lineage;Gene Transfer Techniques;Polymerase Chain Reaction;Mice;Hematopoietic Stem Cells;Fetal Blood;Graft Survival;Research Support, Non-U.S. Gov't}, Medline = {20541502}, Month = {12}, Nlm_Id = {7603509}, Number = {12}, Organization = {Department for Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, Lund University, Lund, Sweden.}, Pages = {3725-33}, Pubmed = {11090053}, Title = {Lentiviral gene transfer into primary and secondary NOD/SCID repopulating cells}, Uuid = {6059A270-4F8E-4F7A-8EF1-EE5D64B98533}, Volume = {96}, Year = {2000}} @article{Woods:2003, Abstract = {Efficient vector transduction of hematopoietic stem cells is a requirement for successful gene therapy of hematologic disorders. We asked whether human umbilical cord blood CD34(+)CD38(lo) nonobese diabetic/severe combined immunodeficiency (NOD/SCID) repopulating cells (SRCs) could be efficiently transduced using lentiviral vectors, with a particular focus on the average number of vector copies integrating into these primitive progenitor cells. Mouse bone marrow was analyzed by fluorescence-activated cell-sorter scanner and by semiquantitative polymerase chain reaction (PCR) to determine the transduction efficiency into SRCs. Lentiviral vector transduction resulted in an average of 22\%(range, 3\%-90\%) of the human cells expressing green fluorescent protein (GFP), however, multiple vector copies were present in human hematopoietic cells, with an average of 5.6 +/- 3.3 (n = 12) copies per transduced cell. To confirm the ability of lentiviral vectors to integrate multiple vector copies into SRCs, linear amplification mediated (LAM)-PCR was used to analyze the integration site profile of a selected mouse showing low-level engraftment and virtually all human cells expressing GFP. Individually picked granulocyte macrophage colony-forming unit colonies derived from the bone marrow of this mouse were analyzed and shown to have the same 5 vector integrants within each colony. Interestingly, one integration site of the 5 that were sequenced in this mouse was located in a known tumor-suppressor gene, BRCA1. Therefore, these findings demonstrate the ability of lentiviral vectors to transduce multiple copies into a subset of NOD/SCID repopulating cells. While this is efficient in terms of transduction and transgene expression, it may increase the risk of insertional mutagenesis.}, Author = {Woods, Niels-Bjarne B. and Muessig, Arne and Schmidt, Manfred and Flygare, Johan and Olsson, Karin and Salmon, Patrick and Trono, Didier and von Kalle, Christof and Karlsson, Stefan}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Research Support, Non-U.S. Gov't;Mice, Inbred NOD;ADP-ribosyl Cyclase;Colony-Forming Units Assay;Macrophages;Granulocytes;Transfection;Animals;Humans;Stem Cell Transplantation;Lentivirus;Antigens, CD;Mice, SCID;Antigens, CD34;11 Glia;Green Fluorescent Proteins;Genes, Tumor Suppressor;Genetic Vectors;Bone Marrow Cells;Flow Cytometry;Polymerase Chain Reaction;Fetal Blood;Virus Integration;Mice;Luminescent Proteins;Mutagenesis, Insertional}, Medline = {22446452}, Month = {2}, Nlm_Id = {7603509}, Number = {4}, Organization = {Department for Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, Lund University, Sweden.}, Pages = {1284-9}, Pii = {2002-07-2238}, Pubmed = {12393514}, Title = {Lentiviral vector transduction of NOD/SCID repopulating cells results in multiple vector integrations per transduced cell: risk of insertional mutagenesis}, Uuid = {3C5A9790-3576-4F2E-9582-67DABA9F5D16}, Volume = {101}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood-2002-07-2238}} @article{Wootton:2005, Abstract = {Ecologists would like to explain general patterns observed across multi-species communities, such as species-area and abundance-frequency relationships, in terms of the fundamental processes of birth, death and migration underlying the dynamics of all constituent species. The unified neutral theory of biodiversity and related theories based on these fundamental population processes have successfully recreated general species-abundance patterns without accounting for either the variation among species and individuals or resource-releasing processes such as predation and disturbance, long emphasized in ecological theory. If ecological communities can be described adequately without estimating variation in species and their interactions, our understanding of ecological community organization and the predicted consequences of reduced biodiversity and environmental change would shift markedly. Here, I introduce a strong method to test the neutral theory that combines field parameterization of the underlying population dynamics with a field experiment, and apply it to a rocky intertidal community. Although the observed abundance-frequency distribution of the system follows that predicted by the neutral theory, the neutral theory predicts poorly the field experimental results, indicating an essential role for variation in species interactions.}, Author = {Wootton, J. Timothy}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Models, Biological;research support, non-u.s. gov't;Population Dynamics;Species Specificity;Stochastic Processes;Ecology;research support, u.s. gov't, non-p.h.s.;Bivalvia;Biodiversity;Animals;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {0410462}, Number = {7023}, Organization = {Department of Ecology and Evolution, The University of Chicago, 1101 East 57th Street, Chicago, Illinois 60637, USA. twootton\@uchicago.edu}, Pages = {309-12}, Pii = {nature03211}, Pubmed = {15662423}, Title = {Field parameterization and experimental test of the neutral theory of biodiversity}, Uuid = {B0A39236-8D56-4D63-A97F-0D642B2A4F82}, Volume = {433}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03211}} @article{Wrana:2000, Author = {Wrana, J. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Cell}, Keywords = {Trans-Activators/*genetics/*metabolism;C;Gene Expression Regulation, Developmental/physiology;Animal;DNA-Binding Proteins/*genetics/*metabolism;Signal Transduction/*genetics;04 Adult neurogenesis factors;Bone Morphogenetic Proteins/genetics/metabolism;Transforming Growth Factor beta/genetics/metabolism}, Number = {2}, Organization = {Department of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada.}, Pages = {189-92.}, Title = {Regulation of Smad activity}, Uuid = {56C81843-D727-4C80-9975-007F897F2376}, Volume = {100}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10660041}} @article{Wright:1968, Author = {Wright, F. S. and Bradley, W. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0013-4694}, Journal = {Electroencephalogr Clin Neurophysiol}, Keywords = {Penicillins;Epilepsy;Computers;Electroencephalography;Axons;21 Neurophysiology;21 Epilepsy;24 Pubmed search results 2008;Time Factors;Motor Activity;Rabbits;Animals, Newborn;Humans;Animals;Cerebral Cortex;Infant, Newborn;Neurons}, Medline = {69030169}, Month = {9}, Nlm_Id = {0375035}, Number = {3}, Pages = {259-65}, Pubmed = {4176929}, Title = {Maturation of epileptiform activity}, Uuid = {5174F869-3B76-4B95-99D4-D079C17CCB92}, Volume = {25}, Year = {1968}} @article{Wu:2000a, Abstract = {The twitcher mouse is a murine model of globoid cell leukodystropy, a genetic demyelinating disease caused by a mutation of the galactosylceramidase gene. Demyelination of the central nervous system commences around 20 postnatal days. Using GFP-transgenic mice as donors, the distribution of hematogenous cells after bone marrow transplantation was investigated in the twitcher mice. Bone marrow transplantation was carried out at 8 postnatal days. In twitcher chimeric mice examined before 30 postnatal days, numerous GFP(+) cells were detected in spleen and peripheral nerve but only a few were detected in the liver, lung, and spinal white matter. In contrast, at 35 to 40 postnatal days when demyelination is evident, many GFP(+) cells with ameboid form were detected in the white matter of the spinal cord, brainstem, and cerebrum. Approximately half of these GFP(+) cells were co-labeled with Mac-1. In twitcher chimeric mice examined after 100 postnatal days, the majority of GFP/Mac-1 double-positive cells displayed the morphological features of ramified microglia with fine delicate processes and was distributed diffusely in both gray and white matter. These results suggest that a significant number of donor hematogenous cells are able to infiltrate into the brain parenchyma, repositioning themselves into areas previously occupied by microglia, and to ameliorate lethality.}, Author = {Wu, Y. P. and McMahon, E. and Kraine, M. R. and Tisch, R. and Meyers, A. and Frelinger, J. and Matsushima, G. K. and Suzuki, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {Tissue Distribution;Animals;Blood Cells;Viscera;Bone Marrow Transplantation;Postoperative Care;Indicators and Reagents;Mice, Transgenic;Reference Values;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Mice, Neurologic Mutants;Research Support, U.S. Gov't, P.H.S.;Tissue Donors;Mice;Central Nervous System;Luminescent Proteins;Peripheral Nerves}, Medline = {20313103}, Month = {6}, Nlm_Id = {0370502}, Number = {6}, Organization = {Department of Pathology and Laboratory Medicine, the University of North Carolina, Chapel Hill 27599-7525, USA.}, Pages = {1849-54}, Pubmed = {10854208}, Title = {Distribution and characterization of GFP(+) donor hematogenous cells in Twitcher mice after bone marrow transplantation}, Uuid = {E4E156CC-1E30-48AB-A65D-6A01CC9C8ED4}, Volume = {156}, Year = {2000}} @article{Wu:2005, Abstract = {Macrophages/microglia are implicated in spinal cord injury but their precise role in the process is not clear. Our previous studies have reported that radial glia (RG) possess properties of neural stem cells and remerged after central nervous system (CNS) injury which may play an important role in neural repair and regeneration. In the present study, we examined the expression of ED1 (a specific marker for activated macrophages/microglia) and RG in a spinal cord injury (SCI) model and detected the activation at 1, 4, 8, and 12 weeks in both dorsal funiculus and ventral white matter after SCI. For both ED1-positive cells and RG cells, there was a gradual increase in density and in number from 1 to 4 weeks followed by down-regulation up to 12 weeks after injury. The morphologies of macrophages and radial glia were different. However, some ED1-positive cells were also stained by RG marker. These results suggest that macrophages may have some lineage to radial glial cells.}, Author = {Wu, and Miyamoto, and Shibuya, and Mori, and Norimatsu, and Janjua, and Itano,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {0045503}, Organization = {Department of Orthopaedic Surgery, School of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kagawa 761-0793, Japan.}, Pii = {S0006-8993(05)00789-4}, Pubmed = {15993386}, Title = {Co-expression of radial glial marker in macrophages/microglia in rat spinal cord contusion injury model}, Uuid = {88655040-1933-445E-A22D-9E11FFA00E87}, Year = {2005}, url = {papers/Wu_BrainRes2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.brainres.2005.05.054}} @article{Wu:2007, Abstract = {Microglial cells are the resident macrophages that are involved in brain injuries and infections. Recent studies using transcranial two-photon microscopy have shown that ATP and P2Y receptors mediated rapid chemotactic responses of miroglia to local injury. However, the molecular mechanism for microglial chemotaxis toward ATP is still unknown. To address this question, we employed a combination of simultaneous perforated whole-cell recordings and time-lapse confocal imaging in GFP-labeled microglia in acute brain slices from adult mice. We found that ATP-induced rapid chemotaxis is correlated with P2Y receptor associated-outward potassium current in microglia. Activation of both P2Y receptor and its associated potassium channels are required for ATP-induced chemotaxis and baseline motility of microglial cells. The chemotaxis required the activation of phosphoinositide 3-kinase but not mitogen-activated protein kinase pathway. Our results provide strong evidence that P2Y receptor-associated outward potassium channels and the phosphoinositide 3-kinase pathway are important for ATP-induced microglial motility in acute brain slices. (c) 2007 Wiley-Liss, Inc.}, Author = {Wu, and Vadakkan, and Zhuo,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {11 Glia;24 Pubmed search results 2008}, Month = {3}, Nlm_Id = {8806785}, Organization = {Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.}, Pubmed = {17357150}, Title = {ATP-induced chemotaxis of microglial processes requires P2Y receptor-activated initiation of outward potassium currents}, Uuid = {0A74AFB2-1464-4095-B916-0A024F6CDCDC}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20500}} @article{Wu:1994, Abstract = {The present study describes the ultrastructural localization and labelling pattern of lectin in different microglial cell phenotypes in the postnatal rat brain using the isolectin, GSA I-B4. The nascent round and amoeboid microglial cells (round cells and cells displaying short processes) were labelled at their cytoplasmic membrane and the membrane of the subplasmalemmal vacuoles. In the course of their transformation into ramified forms with age, dense lectin labelling was observed successively at different sites in the differentiating cells. The most striking feature was the staining of the Golgi saccules on the trans face, the trans tubular network and associated vesicles and vacuoles in the 'intermediate' ramified microglia (ramified cells bearing thick and long processes and those with thin and long processes). The vacuoles with accumulated reaction products were closely associated with many microtubules extending into the cytoplasmic processes. At the surface, the lectin-labelled vacuoles and vesicles appeared to fuse with the membrane and their contents communicated with the exterior. In the advanced or most differentiated ramified microglial cells (cells bearing attenuated processes), the lectin staining at all the above mentioned sites became diminished. In conclusion, in the transformation of the round microglia into their ramified derivatives, the glycoconjugates at the cytoplasmic membrane are progressively reduced. It is postulated from this study that the down-regulation of the glycoconjugates of the microglial plasma membrane is due primarily to their internalization during endocytosis. This process would trigger a de novo galactosyl protein synthesis and/or modification at the trans Golgi saccules and trans tubular network probably in an attempt to degrade the internalized membrane glycoproteins or to replenish the consumption of the membrane glycoconjugates.}, Author = {Wu, C. H. and Wen, C. Y. and Shieh, J. Y. and Ling, E. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0300-4864}, Journal = {J Neurocytol}, Keywords = {G;Organelles;Animals;Aging;Rats;Vacuoles;Brain;Microglia;Cell Membrane;Rats, Wistar;11 Glia;Animals, Newborn;Membrane Glycoproteins;Endocytosis;Microscopy, Electron;24 Pubmed search results 2008;Intracellular Membranes;Lectins;Research Support, Non-U.S. Gov't}, Medline = {94308820}, Month = {4}, Nlm_Id = {0364620}, Number = {4}, Organization = {Department of Anatomy, College of Medicine, National Taiwan University, Taipei.}, Pages = {258-69}, Pubmed = {8035208}, Title = {Down-regulation of membrane glycoprotein in amoeboid microglia transforming into ramified microglia in postnatal rat brain}, Uuid = {11E54057-E1E9-11DA-9DD9-000D9346EC2A}, Volume = {23}, Year = {1994}} @article{Wu:2001, Abstract = {We have examined the spatiotemporal properties of ensemble activity, an evoked all-or-none polysynaptic activity in rat neocortical slices. Ensemble activity occurred in cortical slices bathed in normal artificial cerebrospinal fluid (ACSF) and was evoked by a single electrical shock either to the white matter or directly to the cortical tissue. This activity was seen in slices of somatosensory and auditory cortices; in other cortical areas we have not been able to evoke it. The activity developed 10 to 250 ms poststimulus and lasted 280 +/- 120 ms in local field potential (LFP) recordings. Voltage-sensitive dye imaging showed that this activity was an area of activation 0.8 +/- 0.4 mm wide that propagated slowly (11.4 +/- 6.2 mm/s, n = 60, 6 animals) in the horizontal direction. Due to this propagation, the actual duration in the whole tissue may be longer (approximately 400 ms) than that recorded by a single LFP electrode. Ensemble activity produced a low-amplitude optical signal (7-14\%of the interictal-like spikes in the same tissue), suggesting a moderate net depolarization of the population. These were very different from hyperexcitable (epileptiform) events in the same tissue that had about 10 times the optical signal amplitude and propagated at 125 +/- 24 mm/s (n = 21, 6 animals). On a global spatial scale (approximately 0.8 mm wide in layers II-III) ensemble activity had a smooth waveform in voltage-sensitive dye signals (population transmembrane potential). On a local scale, field potential recordings showed large fluctuations with complex oscillations and substantial trial-to-trial variation. This suggests that oscillations in cortical circuits occurred only in small clusters of correlated neurons. Ensemble activity was sensitive to the excitation-inhibition balance of the local network. Antagonists of N-methyl-D-aspartate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and GABAa receptors, and muscarinic agonists and other modest manipulations such as increasing bath concentration of Mg(2+) to 2.5-4 mM (normally at 2 mM), or K(+) to 5-7 mM (normally 3 mM), all significantly reduced the probability of evoking the activity. The metabotropic glutamate receptor agonist, aminocyclopentane-1,3-dicarboxylic acid, blocked the activity at a low concentration (10-15 microM), while the antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine had no effect even at high concentration (240 microM). Our data suggest that locally organized neuronal clusters may play a role in the organization of oscillatory activities in the gamma band and may participate in cortical integration/amplification occurring on a scale of approximately 1 mm x 300 ms.}, Author = {Wu, J. Y. and Guan, L. and Bai, L. and Yang, Q.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Excitatory Amino Acid Antagonists;Electric Stimulation;Animals;In Vitro;Evoked Potentials;Rats;Neural Conduction;21 Epilepsy;Female;Cell Count;Rats, Sprague-Dawley;Reaction Time;Time Factors;Bicuculline;Male;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Neurons;Somatosensory Cortex;Convulsants;Auditory Cortex;24 Pubmed search results 2008;Receptors, Metabotropic Glutamate;Research Support, Non-U.S. Gov't}, Medline = {21555311}, Month = {11}, Nlm_Id = {0375404}, Number = {5}, Organization = {Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA. wuj\@georgetown.edu}, Pages = {2461-74}, Pubmed = {11698535}, Title = {Spatiotemporal properties of an evoked population activity in rat sensory cortical slices}, Uuid = {4828FB2F-6E46-4698-B964-47886E8AED00}, Volume = {86}, Year = {2001}} @article{Wu:2002, Abstract = {Pluripotent or multipotent stem cells isolated from human embryos or adult central nervous system (CNS) may provide new neurons to ameliorate neural disorders. A major obstacle, however, is that the majority of such cells do not differentiate into neurons when grafted into non-neurogenic areas of the adult CNS. Here we report a new in vitro priming procedure that generates a nearly pure population of neurons from fetal human neural stem cells (hNSCs) transplanted into adult rat CNS. Furthermore, the grafted cells differentiated by acquiring a cholinergic phenotype in a region-specific manner. This technology may advance stem cell-based therapy to replace lost neurons in neural injury or neurodegenerative disorders. 1097-6256 Journal Article}, Author = {Wu, P. and Tarasenko, Y. I. and Gu, Y. and Huang, L. Y. and Coggeshall, R. E. and Yu, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Nat Neurosci}, Keywords = {Fetus;Heparin/pharmacology;Human;Animals;Cells, Cultured;Rats;Nerve Growth Factors/pharmacology;Laminin/pharmacology;Cell Culture/*methods;Phenotype;L pdf;Neurodegenerative Diseases/*therapy;Choline O-Acetyltransferase/metabolism;17 Transplant Regeneration;Male;Brain Tissue Transplantation/*methods;Stem Cells/*cytology/drug effects/metabolism;Neurons/*cytology/drug effects/metabolism;Support, Non-U.S. Gov't;Graft Survival/drug effects/*physiology;Acetylcholine/metabolism;Stem Cell Transplantation/*methods;Support, U.S. Gov't, P.H.S.;Immunohistochemistry}, Number = {12}, Organization = {Department of Anatomy, University of Texas Medical Branch, Galveston, Texas 77555, USA. piwu\@utmb.edu}, Pages = {1271-8}, Title = {Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat}, Uuid = {A8B38E9F-5444-403E-B80E-5B4BD4FA2151}, Volume = {5}, Year = {2002}, url = {papers/Wu_NatNeurosci2002}} @article{Wu:2000, Abstract = {Immunocytochemical studies of postmortem human tissue have shown that the neurons at risk for degeneration in Alzheimer's are marked by the ectopic expression of several cell cycle components. The current work investigates the roles that beta-amyloid activated microglia might play in leading neurons to re-express cell cycle components. Stable cultures of E16.5 mouse cortical neurons were exposed to beta-amyloid alone, microglial cells alone, or microglial cells activated by beta-amyloid. Increased cell death was found in response to each of these treatments, however, only the amyloid activated microglial treatment increased the number of neurons that were positive for cell cycle markers such as PCNA or cyclin D and incorporation of BrdU. Double labeling with BrdU and TUNEL techniques verified that the 'dividing' neurons were dying, most likely through an apoptotic mechanism. The identity of the soluble factor(s) elaborated by the microglia remains unknown, but FGF2, a suspected neuronal mitogen, was ruled out. These results further support a model in which microglial activation by beta-amyloid is a key event in the progression in Alzheimer's disease.}, Author = {Wu, Q. and Combs, C. and Cannady, S. B. and Geldmacher, D. S. and Herrup, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0197-4580}, Journal = {Neurobiol Aging}, Keywords = {Human;Animals;Cells, Cultured;Amyloid beta-Protein;Cell Cycle;Apoptosis;Female;Microglia;Kinetics;Culture Media, Conditioned;Not relevant;Mice, Inbred C57BL;11 Glia;Embryo;Male;Cell Line;Support, Non-U.S. Gov't;Cerebral Cortex;Neurons;Support, U.S. Gov't, P.H.S.;Mice;Cell Division}, Medline = {20574083}, Nlm_Id = {8100437}, Number = {6}, Organization = {Alzheimer Research Laboratory, University Hospitals of Cleveland, Case Western Reserve University, School of Medicine, 10900 Euclid Avenue, Cleveland, OH 44106, USA.}, Pages = {797-806}, Pii = {S0197458000002190}, Pubmed = {11124423}, Title = {Beta-amyloid activated microglia induce cell cycling and cell death in cultured cortical neurons}, Uuid = {83187F85-510C-4806-AC0C-7B0ABFD3AB34}, Volume = {21}, Year = {2000}, url = {papers/Wu_NeurobiolAging2000.pdf}} @article{Wu:2002a, Abstract = {Here we report a novel method of supplying cultured neurosphere cells to the injured spinal cord, by injection of cells into the cerebrospinal fluid (CSF) through the fourth ventricle or cisterna magna. Hippocampus-derived neurosphere cells, isolated from a transgenic rat fetus expressing green fluorescent protein, were transplanted into the CSF of a rat with spinal cord injury. It was found that injected cells were extensively transported by CSF within the subarachnoidal space, and survived as clusters on the pial surface of the spinal cord. The most notable finding was that a large number of injected cells migrated into the lesion site and integrated into the injured spinal cord tissues.}, Author = {Wu, Sufan and Suzuki, Yoshihisa and Kitada, Masaaki and Kataoka, Kazuya and Kitaura, Miyako and Chou, Hirotomi and Nishimura, Yoshihiko and Ide, Chizuka}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {Fetus;Research Support, Non-U.S. Gov't;Animals;Stem Cell Transplantation;Brain Tissue Transplantation;Rats;Recovery of Function;Tubulin;Fourth Ventricle;Indicators and Reagents;Rats, Sprague-Dawley;Hippocampus;Animals, Genetically Modified;Subarachnoid Space;11 Glia;Green Fluorescent Proteins;Cell Movement;Nerve Regeneration;Spinal Cord Injuries;Pia Mater;Cerebrospinal Fluid;Luminescent Proteins;Immunohistochemistry;Graft Survival;Glial Fibrillary Acidic Protein}, Medline = {21655590}, Month = {1}, Nlm_Id = {7600130}, Number = {2}, Organization = {Department of Plastic and Reconstructive Surgery, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8507, Japan.}, Pages = {81-4}, Pii = {S0304394001024880}, Pubmed = {11796191}, Title = {New method for transplantation of neurosphere cells into injured spinal cord through cerebrospinal fluid in rat}, Uuid = {ABBC0D1C-EC9A-4E7E-9AAF-647D15BD2480}, Volume = {318}, Year = {2002}} @article{Wu:2001a, Abstract = {Human umbilical cord blood provides an alternative source of hematopoietic cells for purposes of transplantation or ex vivo genetic modification. The objective of this study was to evaluate electroporation as a means to introduce foreign genes into human cord blood CD34+ cells and evaluate gene expression in CD34+/CD38(dim) and committed myeloid progenitors (CD33+, CD11b+). CD34+ cells were cultured in X-VIVO 10 supplemented with thrombopoietin, stem cell factor, and Flt-3 ligand. Electroporation efficiency and cell viability measured by flow cytometry using enhanced green fluorescent protein (EGFP) as a reporter indicated 31\%+/- 2\%EGFP+ /CD34+ efficiency and 77\%+/- 3\%viability as determined 48 hours post-electroporation. The addition of allogeneic cord blood plasma increased the efficiency to 44\%+/- 5\%with no effect on viability. Of the total CD34+ cells 48 hours post-electroporation, 20\%were CD38(dim)/EGFP+. CD34+ cells exposed to interleukin-3, GM-CSF and G-CSF for an additional 11 days differentiated into CD33+ and CD11b+ cells, and 9\%+/- 3\%and 8\%+/- 7\%were expressing the reporter gene, respectively. We show that electroporation can be used to introduce foreign genes into early hematopoietic stem cells (CD34+/CD38(dim)), and that the introduced gene is functionally expressed following expansion into committed myeloid progenitors (CD33+, CD11b+) in response to corresponding cytokines. Further investigation is needed to determine the transgene expression in functional terminal cells derived from the genetically modified CD34+ cells, such as T cells and dendritic cells.}, Author = {Wu, M. H. and Smith, S. L. and Dolan, M. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:43 -0400}, Issn = {1066-5099}, Journal = {Stem Cells}, Keywords = {ADP-ribosyl Cyclase;Humans;Transfection;Plasma;Antigens, Differentiation;NAD+ Nucleosidase;Antigens, CD;Electroporation;Granulocyte Colony-Stimulating Factor;Antigens, CD34;Recombinant Fusion Proteins;Granulocyte-Macrophage Colony-Stimulating Factor;11 Glia;Green Fluorescent Proteins;Interleukin-3;Research Support, U.S. Gov't, P.H.S.;Hematopoietic Stem Cells;Cell Division;Luminescent Proteins;Fetal Blood;Gene Expression}, Medline = {21570680}, Nlm_Id = {9304532}, Number = {6}, Organization = {Section of Hematology-Oncology, Department of Medicine and Cancer Research Center, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA.}, Pages = {492-9}, Pubmed = {11713340}, Title = {High efficiency electroporation of human umbilical cord blood CD34+ hematopoietic precursor cells}, Uuid = {9EB84240-94A2-4312-884A-F4EE79F08D97}, Volume = {19}, Year = {2001}} @article{Wurmser:2002, Abstract = {0028-0836 Comment News}, Author = {Wurmser, A. E. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Nature}, Keywords = {EE pdf;Embryo/cytology;Neurons/cytology;Human;Bone Marrow Cells/cytology;*Cell Fusion;08 Aberrant cell cycle;*Cell Differentiation;Animals;Stem Cells/*cytology}, Number = {6880}, Pages = {485-7}, Title = {Stem cells: cell fusion causes confusion}, Uuid = {41E98EC3-D3AE-11D9-A0E9-000D9346EC2A}, Volume = {416}, Year = {2002}, url = {papers/Wurmser_Nature2002.pdf}} @article{Wuttke:1972, Author = {Wuttke, W. and Michael, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0031-6768}, Journal = {Pflugers Arch}, Keywords = {Gonadotropins;Rats;Female;Ovulation;Action Potentials;Animals;24 Pubmed search results 2008;Neurons;Frontal Lobe}, Medline = {72256430}, Nlm_Id = {0154720}, Pages = {Suppl 332:R87}, Pubmed = {5065871}, Title = {[Correlation of hypophyseal gonadotropin secretion with neural activity in the medial preoptic region]}, Uuid = {5BF08662-9C51-4A3B-AAB8-1497CB5B0EF7}, Volume = {332}, Year = {1972}} @article{Xiao:2002, Abstract = {Microglia are often considered a type of tissue macrophages analogous Langerhans' cells, while dendritic cells (DC) can be generated in vitro from cultured microglia in the presence of GM-CSF. In this study, we show that TGF-beta 1, in the presence of GM-CSF, promoted the growth and differentiation of glial cell-derived dendritic cells (GC-DC). TGF-beta 1-driven GC-DC exhibited an immature state reflected by low CD11c expression, augmented endocytosis, and reduced antigen presentation. Expression of Fas was inhibited in GM-CSF+TGF-beta 1-supplemented cell cultures and may relate to a long life span of GC-DC treated with GM-CSF+TGF-beta 1. IL-10 and IL-12 mRNA on GC-DC was not affected upon exposure to GM-CSF alone or to GM-CSF+IFN-gamma, GM-CSF+IL-10 or GM-CSF+TGF-beta 1. In sharp contrast, TGF-beta 1, in the presence of GM-CSF, dramatically up-regulated the expression of TNF-alpha and TGF-beta 1 mRNA. These results demonstrate that TGF-beta 1 seems to play a crucial role in the differentiation, functional skewing, and cytokine profile of GC-DC. TGF-beta 1-driven GC-DC awaits further investigation to facilitate a better understanding of the glia-T cell dialog as well as the pathogenesis and immunotherapy of central nervous system inflammatory and degenerative diseases.}, Author = {Xiao, Bao-Guo G. and Xu, Ling-Yun Y. and Yang, Jian-She S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0889-1591}, Journal = {Brain Behav Immun}, Keywords = {Cell Aging;Drug Synergism;Tumor Necrosis Factor;Cell Differentiation;Rats, Inbred Lew;In Vitro;Animals;Rats;Transforming Growth Factor beta;Cells, Cultured;Dendritic Cells;Not relevant;Granulocyte-Macrophage Colony-Stimulating Factor;11 Glia;RNA, Messenger;Support, Non-U.S. Gov't;Cerebral Cortex;Neuroglia;Gene Expression}, Medline = {22368141}, Month = {12}, Nlm_Id = {8800478}, Notes = {glia culture experiment}, Number = {6}, Organization = {Experimental Neurology Unit, Division of Neurology, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden. bao-guo.xiao\@neurotec.ki.se}, Pages = {685-97}, Pii = {S088915910200020X}, Pubmed = {12480499}, Title = {TGF-beta 1 synergizes with GM-CSF to promote the generation of glial cell-derived dendriform cells in vitro}, Uuid = {C3D9DB43-82BD-4F14-B7B6-40F717B1567D}, Volume = {16}, Year = {2002}, url = {papers/Xiao_BrainBehavImmun2002.pdf}} @article{Xie:2004, Abstract = {Chronic glial activation in neurodegenerative diseases contributes to neuronal dysfunction and neuron loss through production of neuroinflammatory molecules. However, the molecular mechanisms, particularly the signal transduction pathways involved in glia-dependent neuron death, are poorly understood. As a first step to address this question, we used a neuron-glia co-culture system that allows diffusion of soluble molecules between glia and neurons to test the potential importance of mitogen-activated protein kinase (MAPK) signaling pathways in the glia-induced neuron death. Activation of glia in co-culture by lipopolysaccharide (LPS) induced apoptotic-like neuron death. The MAPKs tested (p38, JNK, ERK1/2) were activated in both glia and neurons following LPS treatment, suggesting their involvement in both glial activation and neuronal response to diffusible, glia-derived neurotoxic molecules. Inhibitors of p38 and JNK partially blocked neuron death in the LPS-treated co-culture, whereas an ERK1/2 pathway inhibitor did not protect neurons. These results show that p38 and JNK MAPKs, but not ERK1/2 MAPK, are important signal transduction pathways contributing to glia-induced neuron death.}, Author = {Xie, Zhong and Smith, Carolyn J. and Van Eldik, Linda J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Interferons;Neurodegenerative Diseases;Alpha;Reaction Time;Animals;Cells, Cultured;Lipopolysaccharides;Nitric-Oxide Synthase;MAP Kinase Signaling System;Interleukin-1;Mitochondria;Mice, Inbred C57BL;Membrane Potentials;Gliosis;11 Glia;Cell Communication;Not relevant;Rats, Sprague-Dawley;07 Excitotoxicity Apoptosis;Enzyme Inhibitors;Neuroglia;Cell Death;Rats;Fetus;Microglia;Encephalitis;Mice;Mitogen-Activated Protein Kinases;Coculture;Neurons;Fluorescent Dyes}, Month = {1}, Nlm_Id = {8806785}, Number = {2}, Organization = {Department of Cell and Molecular Biology, and Drug Discovery Program, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60612, USA.}, Pages = {170-9}, Pubmed = {14730710}, Title = {Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38}, Uuid = {AEC32F78-ABAA-4E73-9BBF-658109EA98C6}, Volume = {45}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10314}} @article{Xie:2002, Abstract = {Transgenic mice were generated to permit the targeted ablation of cortical preplate cells at the time they are born. In these mice, the 1.3 kb golli promoter of the myelin basic protein gene was used to drive the herpes simplex virus thymidine kinase (TK) transgene in cortical preplate cells. Heterozygous transgenic pairs were bred, and pregnant dams were treated with ganciclovir at embryonic days 11-12 to ablate preplate cells at the time the preplate was forming. This paradigm exposed control (TK-) and experimental (TK+) littermates to exactly the same conditions. Embryological ablation of preplate cells led to an early disruption of the radial glial framework and subplate structure in the developing cortex and dramatically altered the cellular lamination and connectivity of the cortical plate. The disturbed radial glial network contributed to an impaired radial migration of neurons into the cortical plate from the ventricular zone. The cortical plate became dyslaminated, and there was a substantial reduction in short- and long-range cortical projections within the cortex and to subcortical regions. Cell death within the cortical plate and the proliferative zones was substantially increased in the ablated animals. After birth, a cortical lesion developed, which became exacerbated with the secondary onset of hydrocephaly in the second postnatal week. The results underscore the critical importance of the preplate in cortex formation, mediated through its guidance of the formation of radial glial scaffolding, subsequent neuronal migration into the incipient cortical plate, and the final arrangement of its vertical organization and cellular connectivity. 1529-2401 Journal Article}, Author = {Xie, Y. and Skinner, E. and Landry, C. and Handley, V. and Schonmann, V. and Jacobs, E. and Fisher, R. and Campagnoni, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:12:01 -0400}, Journal = {J Neurosci}, Keywords = {Nervous System Malformations/chemically induced/genetics/pathology;Cell Death/drug effects/genetics;Ganciclovir/pharmacology;Animals;10 Development;Neurons/cytology/*drug effects;Cell Movement/drug effects;Promoter Regions (Genetics)/genetics;Mice, Transgenic;F pdf;Hydrocephalus/chemically induced/genetics/pathology;Neuroglia/cytology/drug effects;Myelin Basic Proteins/genetics;In Situ Nick-End Labeling;Cerebral Cortex/cytology/drug effects/*embryology;Simplexvirus/genetics;Support, U.S. Gov't, P.H.S.;Thymidine Kinase/biosynthesis/genetics;Mice;Immunohistochemistry;Models, Animal;Bromodeoxyuridine;Embryonic Structures/cytology/drug effects/*embryology}, Number = {20}, Organization = {Developmental and Molecular Neuroscience Group, Neuropsychiatric Institute, University of California at Los Angeles, School of Medicine, Los Angeles, California 90024-1759, USA.}, Pages = {8981-91}, Title = {Influence of the embryonic preplate on the organization of the cerebral cortex: a targeted ablation model}, Uuid = {780EC16C-F86C-48CC-AE94-B87EF111C9C5}, Volume = {22}, Year = {2002}, url = {papers/Xie_JNeurosci2002.pdf}} @article{Xie:2007, Abstract = {Centrosome- and microtubule-associated proteins have been shown to be important for maintaining the neural progenitor pool during neocortical development by regulating the mitotic spindle. It remains unclear whether these proteins may control neurogenesis by regulating other microtubule-dependent processes such as nuclear migration. Here, we identify Cep120, a centrosomal protein preferentially expressed in neural progenitors during neocortical development. We demonstrate that silencing Cep120 in the developing neocortex impairs both interkinetic nuclear migration (INM), a characteristic pattern of nuclear movement in neural progenitors, and neural progenitor self-renewal. Furthermore, we show that Cep120 interacts with transforming acidic coiled-coil proteins (TACCs) and that silencing TACCs also causes defects in INM and neural progenitor self-renewal. Our data suggest a critical role for Cep120 and TACCs in both INM and neurogenesis. We propose that sustaining INM may be a mechanism by which microtubule-regulating proteins maintain the neural progenitor pool during neocortical development.}, Author = {Xie, Zhigang and Moy, Lily Y. and Sanada, Kamon and Zhou, Ying and Buchman, Joshua J. and Tsai, Li-Huei H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {research support, non-u.s. gov't;research support, n.i.h., extramural;24 Pubmed search results 2008}, Month = {10}, Nlm_Id = {8809320}, Number = {1}, Organization = {Department of Brain and Cognitive Sciences, Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.}, Pages = {79-93}, Pii = {S0896-6273(07)00675-7}, Pubmed = {17920017}, Title = {Cep120 and TACCs control interkinetic nuclear migration and the neural progenitor pool}, Uuid = {F4E6FBA8-7FF2-41BA-B782-C6A4326B6E94}, Volume = {56}, Year = {2007}, url = {papers/Xie_Neuron2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2007.08.026}} @article{Xiong:2002, Abstract = {A unique feature of the olfactory bulb circuit is the long projection of the mitral cell lateral dendrites. Through dendrodendritic reciprocal synapses, these dendrites connect one olfactory glomerular module to hundreds of others; but the functional principles governing these extensive lateral interactions remain largely unknown. Here we report that the spatial extent of action potential propagation in these dendrites is dynamically regulated by inhibitory synapses distributed along the dendrites. The extent of propagation determines the spatial pattern of Ca(2+) influx and thus the range and number of dendrodendritic synapses to be activated. Accordingly, network control of spike traffic in the mitral cell lateral dendrites can mediate dynamic interaction with different combinations of glomerular modules in response to different odorants. 0896-6273 Journal Article}, Author = {Xiong, W. and Chen, W. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Neuron}, Keywords = {13 Olfactory bulb anatomy;Rats, Sprague-Dawley;Dendrites/classification/*physiology;Rats;Female;Synapses/physiology;Olfactory Bulb/*cytology/*physiology;I pdf;Support, U.S. Gov't, P.H.S.;Animals;Support, Non-U.S. Gov't;Male;Ion Channel Gating/*physiology;Action Potentials/*physiology}, Number = {1}, Organization = {Yale University Department of Neurobiology, 333 Cedar Street, C303 SHM, New Haven, CT 06520, USA.}, Pages = {115-26}, Title = {Dynamic gating of spike propagation in the mitral cell lateral dendrites}, Uuid = {EE2D2DF5-68AE-4927-B4B6-4A6B03E10F81}, Volume = {34}, Year = {2002}, url = {papers/Xiong_Neuron2002.pdf}} @article{Xu:2004a, Abstract = {OBJECTIVE: Arterial injury results in vascular remodeling associated with proliferation and migration of smooth muscle cells (SMCs) and the development of intimal hyperplasia, which is a critical component of restenosis after angioplasty of human coronary arteries and an important feature of atherosclerotic lesions. However, the origin of SMCs and other cells in the development of vascular remodeling is not yet fully understood. METHODS AND RESULTS: We utilized a cuff-induced vascular injury model after transplantation of the bone marrow (BM) from green fluorescent protein (GFP)-transgenic mice. We found that macrophages were major cells recruited to the adventitia of the vascular injury lesion along with SMCs and endothelial cells (ECs). While investigating whether those cells are derived from the donor, we found that most of the macrophages were GFP-positive, and some of the SMCs and ECs were also GFP-positive. Administration of the anti-c-fms antibody resulted in a marked decrease in macrophages and a relative increase of SMCs, while administration of antibodies against the platelet-derived growth factor receptor-beta caused a prominent decrease in SMCs and a relative increase in macrophages. CONCLUSIONS: The current study indicates that BM-derived cells play an important role in vascular injury, and that differentiation of macrophages and SMCs might be dependent on each other.}, Author = {Xu, Yang and Arai, Hidenori and Zhuge, Xin and Sano, Hideto and Murayama, Toshinori and Yoshimoto, Momoko and Heike, Toshio and Nakahata, Tatsutoshi and Nishikawa, Shin-ichi and Kita, Toru and Yokode, Masayuki}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1524-4636}, Journal = {Arterioscler Thromb Vasc Biol}, Keywords = {Cell Differentiation;Wound Healing;Animals;Macrophages;Bone Marrow Transplantation;Endothelial Cells;Receptor, Macrophage Colony-Stimulating Factor;Female;Cell Movement;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Radiation Chimera;Femoral Artery;Bone Marrow Cells;Cell Lineage;Antibodies, Monoclonal;Mice;Stem Cells;Constriction;Receptor, Platelet-Derived Growth Factor beta;Myocytes, Smooth Muscle;Research Support, Non-U.S. Gov't}, Month = {3}, Nlm_Id = {9505803}, Number = {3}, Organization = {Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.}, Pages = {477-82}, Pii = {01.ATV.0000118016.94368.35}, Pubmed = {14739121}, Title = {Role of bone marrow-derived progenitor cells in cuff-induced vascular injury in mice}, Uuid = {2471BFD1-25BD-4C5C-B120-333B7744190F}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.ATV.0000118016.94368.35}} @article{Xu:2007, Abstract = {The retina contains two distinct populations of monocyte-derived cells: perivascular cells (macrophages) and parenchymal cells (microglia), important in homeostasis, neuroinflammation, degeneration, and injury. The turnover of these cells in the retina and their repopulation in normal physiological conditions have not been clarified. Bone marrow (BM) cells from EGFP-transgenic mice were adoptively transferred into lethally irradiated normal adult C57BL/6 mice. Eight, 14, and 26 weeks later mice were sacrificed and retinal flatmounts were prepared. Retinal microglia were identified by F4/80, CD45, and Iba-1 immunostaining. BrdU was injected into normal mice for 3-14 days and cell proliferation was examined by confocal microscopy of retinal flatmounts. Few (6.15 +/- 2.02 cells/retina) BrdU(+) cells were detected and of these some coexpressed CD11b (1.67 +/- 0.62 cells/retina) or F4/80 (0.57 +/- 0.30 cells/retina). BM-derived EGFP(+) cells were detected by 8-weeks post-transplantation. By 6 months, all retinal myeloid cells were EGFP(+). Consecutively, donor BM-EGFP(+) cells were demonstrated within the: (1) peripheral and juxtapapillary retina, (2) ganglion cell layer, (3) inner and outer plexiform layers, and (4) photoreceptor layer. EGFP(+) cells within the ganglion layer were amoeboid in shape and F4/80(high)CD45(high)Iba-1(high), whereas cells in the inner and outer plexiform layers were ramified and F4/80(low) CD45(low)Iba-1(low). Perivascular macrophages expressed less F4/80, CD45, and Iba-1 compared with parenchymal microglia. Our results suggest that BM-derived monocyte precursor cells are able to migrate across the BRB and replace retinal microglia/macrophages. The complete replacement of retinal microglia/macrophages takes about 6 months. In situ proliferation was predominantly of nonhemopoetic retinal cells.}, Author = {Xu, Heping and Chen, Mei and Mayer, Eric J. and Forrester, John V. and Dick, Andrew D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Retina;Antigens, CD45;Animals;Macrophages;Bone Marrow Transplantation;Microscopy, Confocal;Microglia;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;research support, non-u.s. gov't;Cell Proliferation;Green Fluorescent Proteins;Antimetabolites;Bone Marrow Cells;Cell Lineage;Antigens, CD11b;Mice;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine;Tissue Fixation}, Month = {8}, Nlm_Id = {8806785}, Number = {11}, Organization = {Department of Ophthalmology, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK. h.xu\@abdn.ac.uk}, Pages = {1189-98}, Pubmed = {17600341}, Title = {Turnover of resident retinal microglia in the normal adult mouse}, Uuid = {0D082641-89BF-4841-91FB-11FB3A46AC45}, Volume = {55}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.20535}} @article{Xu:2004, Abstract = {Cerebral cortical functions are conducted by two general classes of neurons: glutamatergic projection neurons and GABAergic interneurons. Distinct interneuron subtypes serve distinct roles in modulating cortical activity and can be differentially affected in cortical diseases, but little is known about the mechanisms for generating their diversity. Recent evidence suggests that many cortical interneurons originate within the subcortical telencephalon and then migrate tangentially into the overlying cortex. To test the hypothesis that distinct interneuron subtypes are derived from distinct telencephalic subdivisions, we have used an in vitro assay to assess the developmental potential of subregions of the telencephalic proliferative zone (PZ) to give rise to neurochemically defined interneuron subgroups. PZ cells from GFP+ donor mouse embryos were transplanted onto neonatal cortical feeder cells and assessed for their ability to generate specific interneuron subtypes. Our results suggest that the parvalbumin- and the somatostatin-expressing interneuron subgroups originate primarily within the medial ganglionic eminence (MGE) of the subcortical telencephalon, whereas the calretinin-expressing interneurons appear to derive mainly from the caudal ganglionic eminence (CGE). These results are supported by findings from primary cultures of cortex from Nkx2.1 mutants, in which normal MGE fails to form but in which the CGE is less affected. In these cultures, parvalbumin- and somatostatin-expressing cells are absent, although calretinin-expressing interneurons are present. Interestingly, calretinin-expressing bipolar interneurons were nearly absent from cortical cultures of Dlx1/2 mutants. By establishing spatial differences in the origins of interneuron subtypes, these studies lay the groundwork for elucidating the molecular bases for their distinct differentiation pathways. 1529-2401 Journal Article}, Author = {Xu, Q. and Cobos, I. and De La Cruz, E. and Rubenstein, J. L. and Anderson, S. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {J Neurosci}, Keywords = {10 Development;F pdf}, Number = {11}, Organization = {Department of Psychiatry, Weill Medical College of Cornell University, New York, New York 10021, USA.}, Pages = {2612-22}, Title = {Origins of cortical interneuron subtypes}, Uuid = {CE76422E-043A-4C1D-8AAF-1641BB46C3C4}, Volume = {24}, Year = {2004}, url = {papers/Xu_JNeurosci2004.pdf}} @article{Xu:1999, Abstract = {The restriction of intermingling between specific cell populations is crucial for the maintenance of organized patterns during development. A striking example is the restriction of cell mixing between segments in the insect epidermis and the vertebrate hindbrain that may enable each segment to maintain a distinct identity. In the hindbrain, this is a result of different adhesive properties of odd- and even-numbered segments (rhombomeres), but an adhesion molecule with alternating segmental expression has not been found. However, blocking experiments suggest that Eph-receptor tyrosine kinases may be required for the segmental restriction of cells. Eph receptors and their membrane-bound ligands, ephrins, are expressed in complementary rhombomeres and, by analogy with their roles in axon pathfinding, could mediate cell repulsion at boundaries. Remarkably, transmembrane ephrins can themselves transduce signals, raising the possibility that bi-directional signalling occurs between adjacent ephrin- and Eph-receptor-expressing cells. We report here that mosaic activation of Eph receptors leads to sorting of cells to boundaries in odd-numbered rhombomeres, whereas mosaic activation of ephrins results in sorting to boundaries in even-numbered rhombomeres. These data implicate Eph receptors and ephrins in the segmental restriction of cell intermingling. 0028-0836 Journal Article}, Author = {Xu, Q. and Mellitzer, G. and Robinson, V. and Wilkinson, D. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Nature}, Keywords = {Receptor Protein-Tyrosine Kinases/genetics/*metabolism;10 Development;Signal Transduction;Animals;Phosphorylation;Cell Movement;Rhombencephalon/embryology;Central Nervous System/cytology/embryology;Membrane Proteins/*metabolism;F both;Support, Non-U.S. Gov't;Receptor, EphA4;Mosaicism;Fetal Proteins/metabolism;Ephrin-A4;Receptor, EphB2;Zebrafish;Cell Differentiation/physiology}, Number = {6733}, Organization = {Division of Developmental Neurobiology, National Institute for Medical Research, London, UK.}, Pages = {267-71}, Pubmed = {10353250}, Title = {In vivo cell sorting in complementary segmental domains mediated by Eph receptors and ephrins}, Uuid = {D9E1E780-1F84-4BF9-8BCF-A6B99AEB6AAD}, Volume = {399}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10353250}} @article{Xu:1997, Abstract = {In the adult CNS, proliferating cells persist only in the olfactory epithelium, olfactory bulb and subventricular zones. The cells of the subventricular zone are believed to constitute the cells in the adult mammalian brain, including the human brain, which can be stimulated to proliferate in response to epidermal growth factor or basic fibroblast growth factor. These cells are of particular interest, as they may be amenable to genetic engineering with markers such as tyrosine hydroxylase, and they may represent a long-term source of modified neurons suitable for transplantation therapy. Recent work by Lois and Alvarez-Buylla, in the mouse, has shown that labelled subventricular zone cells can migrate from the subventricular zone to the olfactory bulb, where they contribute to the granule cell population. In this study we have used an antibody we raised recently against the carboxy- terminal sequence of the vesicular monoamine transporter 2 (also known as the synaptic vesicle monoamine transporter) to detect vesicular monoamine transporter 2-like immunoreactive subventricular zone cells in the rat, and to visualize them as they migrate from the edge of the ventricle, through the olfactory bulb to locate them as differentiated neurons in the granule cell layer of the olfactory bulb. These data show that the subventricular zone cells express a vesicular monoamine transporter 2-like antigen and demonstrate that this protein may be a useful developmental marker for rat neuronal stem cells.}, Author = {Xu, W. and Emson, P. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuroscience}, Keywords = {Membrane Glycoproteins/*metabolism;Cerebral Ventricles/metabolism;Neurons/*metabolism;Rats;Stem Cells/*metabolism;Animal;04 Adult neurogenesis factors;Fluorescent Antibody Technique;Support, Non-U.S. Gov't;C abstr}, Number = {1}, Organization = {MRC Molecular Neuroscience Group, Babraham Institute, Cambridge, U.K.}, Pages = {7-10.}, Title = {Neuronal stem cells express vesicular monoamine transporter 2 immunoreactivity in the adult rat}, Uuid = {786F4CB5-5115-4AC9-8FCA-812850C6F41D}, Volume = {76}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8971754}} @article{Yagi:2005, Abstract = {Osteoclasts are bone-resorbing cells that play a pivotal role in bone remodeling. Osteoclasts form large multinuclear giant cells by fusion of mononuclear osteoclasts. How cell fusion is mediated, however, is unclear. We identify the dendritic cell-specific transmembrane protein (DC-STAMP), a putative seven-transmembrane protein, by a DNA subtraction screen between multinuclear osteoclasts and mononuclear macrophages. DC-STAMP is highly expressed in osteoclasts but not in macrophages. DC-STAMP-deficient mice were generated, and osteoclast cell fusion was completely abrogated in homozygotes despite normal expression of osteoclast markers and cytoskeletal structure. As osteoclast multinucleation was restored by retroviral introduction of DC-STAMP, loss of cell fusion was directly attributable to a lack of DC-STAMP. Defects in osteoclast multinucleation reduce bone-resorbing activity, leading to osteopetrosis. Similar to osteoclasts, foreign body giant cell formation by macrophage cell fusion was also completely abrogated in DC-STAMP-deficient mice. We have thus identified an essential regulator of osteoclast and macrophage cell fusion, DC-STAMP, and an essential role of osteoclast multinucleation in bone homeostasis.}, Author = {Yagi, Mitsuru and Miyamoto, Takeshi and Sawatani, Yumi and Iwamoto, Katsuya and Hosogane, Naobumi and Fujita, Nobuyuki and Morita, Kozo and Ninomiya, Ken and Suzuki, Toru and Miyamoto, Kana and Oike, Yuichi and Takeya, Motohiro and Toyama, Yoshiaki and Suda, Toshio}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0022-1007}, Journal = {J Exp Med}, Keywords = {11 Glia}, Month = {8}, Nlm_Id = {2985109R}, Number = {3}, Organization = {Department of Cell Differentiation, The Sakaguchi Laboratory.}, Pages = {345-51}, Pii = {jem.20050645}, Pubmed = {16061724}, Title = {DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells}, Uuid = {ABC90DEC-0E1D-4FD9-96CF-B566FFE10320}, Volume = {202}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1084/jem.20050645}} @article{Yagi:2004, Abstract = {The twitcher mouse is an authentic murine model of a genetic demyelinating disease globoid cell leukodystrophy. Allogeneic bone marrow transplantation (BMT) in twitcher mice resulted in the clinicopathological improvement. Thus, using green fluorescent protein (GFP) transgenic mice as the donor, we investigated the behavior and fate of the donor cells and the possibility of transdifferentiation of the donor cells into neuroglial cells in the chimeric twitcher mice. GFP(+) cells were found throughout the brain, most conspicuous in the areas of demyelination. The donor GFP(+) cells expressed RCA-1, a marker for microglia/macrophages but were never exceed 70\%of the entire population of the RCA-1(+) microglia/macrophages. There was no convincing evidence that GFP(+) donor cells expressed markers for neurons, astrocytes, or oligodendrocytes. We concluded BMT is therapeutic for this model. However, this effect is not mediated by donor cells transdifferentiation in the brain.}, Author = {Yagi, Takashi and McMahon, Eileen J. and Takikita, Shoichi and Mohri, Ikuko and Matsushima, Glenn K. and Suzuki, Kinuko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0969-9961}, Journal = {Neurobiol Dis}, Keywords = {Animals;Bone Marrow Transplantation;Comparative Study;Female;Mice, Transgenic;Liver;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Hematopoietic Stem Cell Transplantation;Male;Mice, Neurologic Mutants;Genotype;Hematopoietic Stem Cells;Mice;Luminescent Proteins;Demyelinating Diseases;Lung}, Month = {6}, Nlm_Id = {9500169}, Number = {1}, Organization = {Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.}, Pages = {98-109}, Pii = {S0969996104000129}, Pubmed = {15207267}, Title = {Fate of donor hematopoietic cells in demyelinating mutant mouse, twitcher, following transplantation of GFP+ bone marrow cells}, Uuid = {BACAB63E-FB57-45CA-BB21-91D0C0A9D1E9}, Volume = {16}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.nbd.2004.01.002}} @article{Yagi:1993, Abstract = {Mutant mice in which beta-galactosidase gene (lacZ) was inserted into fyn locus were generated by homologous recombination in embryonic stem cells to examine the Fyn expression in the central nervous system. In adult brain, intensive beta-galactosidase activity was observed in olfactory bulb, cerebellum and hippocampus of the limbic system; the subcellular distribution of the activity was apparent not only in cell body but also in neural processes, and homozygous mutant mice live-born displayed an anatomical abnormality in the neural cell layer of the hippocampal formation. In spinal cord it was specifically expressed in dorsal horn, and in brain stem it was more characteristic in the sensory pathway, suggesting roles of Fyn in the sensory nervous network. In the white matter area, it was intense at postnatal day 10 but not detectable in adult, suggesting Fyn's role in myelinization.}, Author = {Yagi, T. and Shigetani, Y. and Okado, N. and Tokunaga, T. and Ikawa, Y. and Aizawa, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Oncogene}, Keywords = {Cerebral Cortex/chemistry/cytology/embryology;Olfactory Bulb/chemistry/cytology/embryology;Heterozygote;Nervous System/chemistry/cytology/embryology;Cerebellum/chemistry/cytology/embryology;Proto-Oncogenes/*genetics;Embryo/chemistry/cytology;04 Adult neurogenesis factors;Gene Expression/genetics;Hippocampus/chemistry/cytology/embryology;Base Sequence;In Vitro;*Brain Chemistry;Molecular Sequence Data;Mice, Inbred C57BL;Mice, Mutant Strains;Spinal Cord/chemistry/cytology/embryology;beta-Galactosidase/genetics/metabolism/physiology;Mice, Inbred CBA;In Situ Hybridization, Fluorescence;Mutation;Animal;Blotting, Western;Proto-Oncogene Proteins/*analysis/*genetics/physiology;Mice, Inbred ICR;Mice;Support, Non-U.S. Gov't;Homozygote;Lac Operon/*genetics;C abstr}, Number = {12}, Organization = {Laboratory of Molecular Oncology, Tsukuba Life Science Center, Institute of Physical and Chemical Research (RIKEN), Ibaraki, Japan.}, Pages = {3343-51.}, Title = {Regional localization of Fyn in adult brain; studies with mice in which fyn gene was replaced by lacZ}, Uuid = {192BCE52-66DA-4E17-8B61-50A73C08D9DF}, Volume = {8}, Year = {1993}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8247536}} @article{Yagita:2002, Abstract = {Both nestin and the neural RNA-binding protein Musashi1 (Msi1) are expressed in neural stem cells in the subventricular zone. Neurogenesis in the hippocampus has received much attention, so we evaluated the expression of Msi1 and nestin in the adult rat hippocampus after transient forebrain ischemia. Both Msi1 and nestin were induced in the reactive astrocytes after ischemia, especially in the CA1 region, until 35 days after ischemia. Induction of both molecules suggested that reactive astrocytes might have immature characteristics. In the subgranular zone (SGZ) of the hippocampal dentate gyrus, Msi1-positive cells formed clusters after ischemia. These cells were labeled by bromodeoxyuridine (BrdU) but did not express glial fibrillary acidic protein. In contrast, very few nestin-positive cells were labeled by BrdU. Our results suggest that neuronal progenitor cells in the SGZ expressed Msi1 but not nestin. 22194563 0360-4012 Journal Article}, Author = {Yagita, Y. and Kitagawa, K. and Sasaki, T. and Miyata, T. and Okano, H. and Hori, M. and Matsumoto, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {J Neurosci Res}, Keywords = {Rats;D-14;Animal;Glial Fibrillary Acidic Protein/analysis;Rats, Wistar;Nerve Tissue Proteins/analysis/*biosynthesis;Antimetabolites;Intermediate Filament Proteins/analysis/*biosynthesis;Male;Support, Non-U.S. Gov't;06 Adult neurogenesis injury induced;Age Factors;RNA-Binding Proteins/analysis/*biosynthesis;Brain Ischemia/*metabolism;Immunohistochemistry;Biological Markers;Bromodeoxyuridine;Hippocampus/chemistry/*metabolism}, Number = {6}, Organization = {Division of Strokology, Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita City, Osaka, Japan.}, Pages = {750-6}, Pubmed = {12205668}, Title = {Differential expression of Musashi1 and nestin in the adult rat hippocampus after ischemia}, Uuid = {15918EE0-FF59-4706-9528-7ADF66CC6F3E}, Volume = {69}, Year = {2002}, url = {papers/Yagita_JNeurosciRes2002}} @article{Yagita:2001, Abstract = {BACKGROUND AND PURPOSE: Recently, there has been great interest in adult neurogenesis. We investigated whether transient forebrain ischemia could influence the proliferation of neuronal progenitor in the subgranular zone (SGZ) of the rat hippocampus and whether aging could influence the neurogenesis after ischemia. METHODS: Male Wistar rats were subjected to 4-vessel occlusion model. We used a bromodeoxyuridine (BrdU) labeling method to identify the postproliferation cells and double-immunostaining with confocal microscopy to determine the cell phenotype. RESULTS: The number of BrdU-positive cells in the SGZ increased approximately 5.7-fold 8 days after ischemia, compared with the control. BrdU-positive cells formed clusters, which suggested that these cells had divided from an original progenitor cell, and expressed Musashi1 (Msi1), a marker of neural stem/progenitor cells. Although astrocytes also expressed Msi1 in the adult brain, Msi1-positive cells that formed clusters in the SGZ did not express glial fibrillary acidic protein, an astrocyte marker. About 70\%of all BrdU-positive cells in the SGZ represented the neuronal phenotype 4 weeks after the BrdU injection. Although proliferation of progenitor cells was stimulated in both young and older animals, aging accelerated the reduction in newborn cells after ischemia. CONCLUSIONS: Our results indicate that ischemic stress stimulated the proliferation of neuronal progenitor cells in the SGZ of both young and old rats but resulted in increased neurogenesis only in young animals. Our findings will be important in developing therapeutic intervention to enhance endogenous neurogenesis after brain injury. 1524-4628 Journal Article}, Author = {Yagita, Y. and Kitagawa, K. and Ohtsuki, T. and Takasawa, Ki and Miyata, T. and Okano, H. and Hori, M. and Matsumoto, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Stroke}, Keywords = {Hippocampus/blood supply/*pathology;Prosencephalon/blood supply/pathology;Glial Fibrillary Acidic Protein/biosynthesis;Animals;Rats;Stem Cells/*cytology/metabolism;Mitosis/physiology;Dentate Gyrus/pathology;Nerve Tissue Proteins/biosynthesis;Cell Count;Rats, Wistar;Disease Models, Animal;Male;Support, Non-U.S. Gov't;D abstr;Astrocytes/cytology/metabolism;Cell Division/physiology;06 Adult neurogenesis injury induced;*Aging/physiology;Ischemic Attack, Transient/*pathology;RNA-Binding Proteins/biosynthesis;Neurons/cytology/metabolism;Bromodeoxyuridine}, Number = {8}, Organization = {Division of Strokology, Department of Internal Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.}, Pages = {1890-6}, Pubmed = {11486122}, Title = {Neurogenesis by progenitor cells in the ischemic adult rat hippocampus}, Uuid = {414076D5-EC81-11DA-8605-000D9346EC2A}, Volume = {32}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11486122}} @article{Yaksi:2006, Abstract = {Methods to record action potential (AP) firing in many individual neurons are essential to unravel the function of complex neuronal circuits in the brain. A promising approach is bolus loading of Ca(2+) indicators combined with multiphoton microscopy. Currently, however, this technique lacks cell-type specificity, has low temporal resolution and cannot resolve complex temporal firing patterns. Here we present simple solutions to these problems. We identified neuron types by colocalizing Ca(2+) signals of a red-fluorescing indicator with genetically encoded markers. We reconstructed firing rate changes from Ca(2+) signals by temporal deconvolution. This technique is efficient, dramatically enhances temporal resolution, facilitates data interpretation and permits analysis of odor-response patterns across thousands of neurons in the zebrafish olfactory bulb. Hence, temporally deconvolved Ca(2+) imaging (TDCa imaging) resolves limitations of current optical recording techniques and is likely to be widely applicable because of its simplicity, robustness and generic principle.}, Author = {Yaksi, Emre and Friedrich, Rainer W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {21 Neurophysiology;24 Pubmed search results 2008;23 Technique}, Month = {5}, Nlm_Id = {101215604}, Number = {5}, Organization = {Max Planck Institute for Medical Research, Department of Biomedical Optics, Jahnstr. 29, 69120 Heidelberg, Germany.}, Pages = {377-83}, Pii = {nmeth874}, Pubmed = {16628208}, Title = {Reconstruction of firing rate changes across neuronal populations by temporally deconvolved Ca(2+) imaging}, Uuid = {D5D050DE-B09A-4C79-B878-652800092D76}, Volume = {3}, Year = {2006}, url = {papers/Yaksi_NatMethods2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth874}} @article{Yamada:1998a, Abstract = {The glutamate transporter GLT-1 is expressed in astrocytes of the mature brain and spinal cord. In the present study, we examined its expression in the developing mouse spinal cord. By in situ hybridization, 35S-labeled antisense oligonucleotide probes for GLT-1 mRNA consistently labeled the mantle zone/gray matter from embryonic day 11 through the adult stage. However, immunohistochemistry with a specific antibody visualized distinct regional and cellular localizations during the time between the fetal and postnatal stages. At fetal stages, GLT-1 immunoreactivity predominated in the marginal zone/white matter, observed as tiny puncta in cross-sections and as thin fibers in longitudinal sections. The GLT-1-immunopositive structures were also labeled for neuron-specific enolase, a glycolytic enzyme specific to postmitotic neurons and endocrine cells. By electron microscopy, GLT-1 immunoreactivity was detected in axons forming frequent enlargements and was focally localized on a small portion of the axolemma, particularly that facing adjacent axons. At early postnatal stages, GLT-1 disappeared from axons in white matter tracts and, instead, appeared in astrocytic processes surrounding various neuronal elements in the gray matter. Therefore, before switching to astrocytic expression, GLT-1 is transiently expressed in neurons and localized in differentiating axons. Together with our previous finding on the localization of glutamate transporter GLAST in radial glial fibers, GLT-1 and GLAST are thus localized during development on distinct directional cellular elements along which young neurons elongate their axons or move their cell bodies, respectively.}, Author = {Yamada, K. and Watanabe, M. and Shibata, T. and Nagashima, M. and Tanaka, K. and Inoue, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Neurosci}, Keywords = {Biological Transport/physiology;ABC Transporters/*analysis;Spinal Cord/*chemistry/embryology/growth &development;Axons/*chemistry;Animal;Antibody Formation;G-need;Mice, Inbred C57BL;11 Glia;Astrocytes/*chemistry;Time Factors;In Situ Hybridization;Support, Non-U.S. Gov't;Mice;Immunohistochemistry;Molecular Sequence Data;Amino Acid Sequence;Neurons/*chemistry/ultrastructure;Nerve Tissue Proteins/*analysis;Fetal Development/physiology}, Number = {15}, Organization = {Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.}, Pages = {5706-13.}, Title = {Glutamate transporter GLT-1 is transiently localized on growing axons of the mouse spinal cord before establishing astrocytic expression}, Uuid = {F1EF68A5-6FCE-430E-B5A2-3E9C56DA4FD1}, Volume = {18}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9671661}} @article{Yamada:1998, Abstract = {Therapeutic strategies for leukemia are directed to induction of differentiation and apoptosis as well as growth inhibition. One of the key antileukemic agents, 1-beta-D-arabinofuranosylcytosine (ara C), is clinically applied according to these therapeutic aims. However, the molecular effects of 0.1 microg/ml of ara C, a concentration that corresponds to the serum level in leukemic patients on a conventional dose of ara C, have not been well disclosed. Here, we addressed these issues using K562 cells which derived from a blastic crisis of chronic myeloid leukemia. DNA synthesis of treated cells was suppressed from 1-6 h. But, it recovered at 12 h and no further inhibition was observed. The number of cells was not decreased but DNA fragmentation was observed at 72 h. The number of erythroid-differentiated cells also increased to 30\%at 72 h. Along with treatment, no marked alteration of mRNAs for cell cycle-regulating genes was found and the retinoblastoma gene product remained hyperphosphorylated throughout treatment. The expression of mRNAs for apoptosis-regulating genes also remained unchanged, except for slight down-regulation of Bax. c-myc protein was not found later than 48 h, and Max mRNA was downregulated. c-jun was immediately induced, followed by the fluctuated expression level along with treatment. These findings suggest that the 0.1 microg/ml ara C changed the proliferation, differentiation and death of K562 cells in a biphasic manner. In the early phase, DNA synthesis was inhibited without altering the expression of cell cycle regulating-genes. In the latter phase, cell death and erythroid- differentiation occurred in accordance with the down-regulation of c-myc. 0300-8177 Journal Article}, Author = {Yamada, H. and Horiguchi-Yamada, J. and Nagai, M. and Takahara, S. and Sekikawa, T. and Kawano, T. and Itoh, K. and Fukumi, S. and Iwase, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Mol Cell Biochem}, Keywords = {Cell Differentiation/drug effects;Human;Benzidines/analysis;Phosphorylation;Comparative Study;Retinoblastoma Protein/metabolism;Genes, myc;Genes, jun;Gene Expression Regulation/drug effects;08 Aberrant cell cycle;DNA Fragmentation/drug effects;Reverse Transcriptase Polymerase Chain Reaction;Cytarabine/*pharmacology/therapeutic use;DNA/biosynthesis;Erythrocytes/*cytology/drug effects;Support, Non-U.S. Gov't;Genes, cdc/genetics;Blotting, Western;Apoptosis/*drug effects/genetics;Cell Cycle/*drug effects;K562 Cells;EE abstr}, Number = {1-2}, Organization = {Department of Internal Medicine (IV), Aoto Hospital, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan.}, Pages = {211-20}, Pubmed = {9788759}, Title = {Biological effects of a relatively low concentration of 1-beta-D-arabinofuranosylcytosine in K562 cells: alterations of the cell cycle, erythroid-differentiation, and apoptosis}, Uuid = {089F6BB3-1A1E-483F-B82B-4524936F6F20}, Volume = {187}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9788759}} @article{Yamagata:2002, Abstract = {A major determinant of specific connectivity in the central nervous system is that synapses made by distinct afferent populations are restricted to particular laminae in their target area. We identify Sidekick (Sdk)-1 and -2, homologous transmembrane immunoglobulin superfamily molecules that mediate homophilic adhesion in vitro and direct laminar targeting of neurites in vivo. sdk-1 and -2 are expressed by nonoverlapping subsets of retinal neurons; each sdk is expressed by presynaptic (amacrine and bipolar) and postsynaptic (ganglion) cells that project to common inner plexiform (synaptic) sublaminae. Sdk proteins are concentrated at synaptic sites, and Sdk-positive synapses are restricted to the 2 (of > or =10) sublaminae to which sdk-expressing cells project. Ectopic expression of Sdk in Sdk-negative cells redirects their processes to a Sdk-positive sublamina. These results implicate Sdks as determinants of lamina-specific synaptic connectivity.}, Author = {Yamagata, Masahito and Weiner, Joshua A. and Sanes, Joshua R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Synapses;Retina;research support, u.s. gov't, p.h.s. ;Neural Cell Adhesion Molecules;Cell Adhesion;21 Neurophysiology;Molecular Sequence Data;Eye Proteins;Membrane Proteins;research support, non-u.s. gov't ;Drosophila Proteins;Amacrine Cells;Amino Acid Sequence;Retinal Ganglion Cells;Animals;Chickens;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {0413066}, Number = {5}, Organization = {Department of Anatomy and Neurobiology, School of Medicine, Washington University, Saint Louis, MO 63110, USA.}, Pages = {649-60}, Pii = {S0092867402009108}, Pubmed = {12230981}, Title = {Sidekicks: synaptic adhesion molecules that promote lamina-specific connectivity in the retina}, Uuid = {CFBAB388-08E2-4128-B869-8F2FCC98CA00}, Volume = {110}, Year = {2002}} @article{Yamagata:2008, Abstract = {Synaptic circuits in the retina transform visual input gathered by photoreceptors into messages that retinal ganglion cells (RGCs) send to the brain. Processes of retinal interneurons (amacrine and bipolar cells) form synapses on dendrites of RGCs in the inner plexiform layer (IPL). The IPL is divided into at least 10 parallel sublaminae; subsets of interneurons and RGCs arborize and form synapses in just one or a few of them. These lamina-specific circuits determine the visual features to which RGC subtypes respond. Here we show that four closely related immunoglobulin superfamily (IgSF) adhesion molecules--Dscam (Down's syndrome cell adhesion molecule), DscamL (refs 6-9), Sidekick-1 and Sidekick-2 (ref. 10)--are expressed in chick by non-overlapping subsets of interneurons and RGCs that form synapses in distinct IPL sublaminae. Moreover, each protein is concentrated within the appropriate sublaminae and each mediates homophilic adhesion. Loss- and gain-of-function studies in vivo indicate that these IgSF members participate in determining the IPL sublaminae in which synaptic partners arborize and connect. Thus, vertebrate Dscams, like Drosophila Dscams, play roles in neural connectivity. Together, our results on Dscams and Sidekicks suggest the existence of an IgSF code for laminar specificity in retina and, by implication, in other parts of the central nervous system.}, Author = {Yamagata, Masahito and Sanes, Joshua R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Retina;10 Development;Animals;Synapses;Humans;Immunoglobulins;Eye Proteins;Gene Expression Profiling;10 circuit formation;Cell Line;Cell Adhesion;Chick Embryo;Organ Specificity;research support, n.i.h., extramural;Interneurons;24 Pubmed search results 2008;Membrane Proteins;Neural Cell Adhesion Molecules}, Month = {1}, Nlm_Id = {0410462}, Number = {7177}, Organization = {Department of Molecular and Cellular Biology and Center for Brain Science, Harvard University, Cambridge, Massachusetts 02138, USA.}, Pages = {465-9}, Pii = {nature06469}, Pubmed = {18216854}, Title = {Dscam and Sidekick proteins direct lamina-specific synaptic connections in vertebrate retina}, Uuid = {36008284-92E1-410F-83DD-A39C99CC0B4C}, Volume = {451}, Year = {2008}, url = {papers/Yamagata_Nature2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature06469}} @article{Yamaguchi:2003, Abstract = {Individual cellular clocks in the suprachiasmatic nucleus (SCN), the circadian center, are integrated into a stable and robust pacemaker with a period length of about 24 hours. We used real-time analysis of gene expression to show synchronized rhythms of clock gene transcription across hundreds of neurons within the mammalian SCN in organotypic slice culture. Differentially phased neuronal clocks are topographically arranged across the SCN. A protein synthesis inhibitor set all cell clocks to the same initial phase and, after withdrawal, intrinsic interactions among cell clocks reestablished the stable program of gene expression across the assemblage. Na+-dependent action potentials contributed to establishing cellular synchrony and maintaining spontaneous oscillation across the SCN.}, Author = {Yamaguchi, Shun and Isejima, Hiromi and Matsuo, Takuya and Okura, Ryusuke and Yagita, Kazuhiro and Kobayashi, Masaki and Okamura, Hitoshi}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Transcription, Genetic;Signal Transduction;Cell Cycle Proteins;Animals;Trans-Activators;Transcription Factors;20 Networks;Cycloheximide;Suppression, Genetic;Basic Helix-Loop-Helix Transcription Factors;Mice, Transgenic;Biological Clocks;research support, non-u.s. gov't;Protein Synthesis Inhibitors;Tetrodotoxin;Organ Culture Techniques;Action Potentials;Glyceraldehyde-3-Phosphate Dehydrogenases;Mice, Knockout;Neurons;Sodium;Nuclear Proteins;Mice;24 Pubmed search results 2008;Luminescence;Promoter Regions (Genetics);Gene Expression;Circadian Rhythm;Suprachiasmatic Nucleus}, Month = {11}, Nlm_Id = {0404511}, Number = {5649}, Organization = {Division of Molecular Brain Science, Department of Brain Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.}, Pages = {1408-12}, Pii = {302/5649/1408}, Pubmed = {14631044}, Title = {Synchronization of cellular clocks in the suprachiasmatic nucleus}, Uuid = {FFA5C5ED-11F4-4BCD-BABB-85E5F043A1CE}, Volume = {302}, Year = {2003}, url = {papers/Yamaguchi_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1089287}} @article{Yamashita:1997, Abstract = {In adult rodents, proliferating cells in the subventricular zone of lateral ventricle tangentially migrate into the olfactory bulb, where they become the interneurons. The present immunocytochemical analysis revealed that S100A6 (calcyclin), a specific calcium-binding protein of the S100 family, is restrictedly distributed in some astrocytes in the tangential migration pathway of the rat. These results suggest that a particular type of astrocytes containing S100A6 is associated with the tangential migration pathway.}, Author = {Yamashita, N. and Kosaka, K. and Ilg, E. C. and Schafer, B. W. and Heizmann, C. W. and Kosaka, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Brain Res}, Keywords = {Microscopy, Confocal;*Cell Movement;G abstr;Rats;Olfactory Bulb/cytology;Calcium-Binding Proteins/*analysis/immunology;Epidermal Growth Factor/analysis/immunology;Rats, Wistar;Cell Communication;11 Glia;Cerebral Ventricles/*cytology;Neurons/*cytology;Animal;Support, Non-U.S. Gov't;Male;Antibodies;Astrocytes/*chemistry/cytology}, Number = {2}, Organization = {Department of Anatomy and Neurobiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.}, Pages = {388-92.}, Title = {Selective association of S100A6 (calcyclin)-immunoreactive astrocytes with the tangential migration pathway of subventricular zone cells in the rat}, Uuid = {E2D1779F-CE62-4D69-8355-A3E83A127744}, Volume = {778}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9459556}} @article{Yan:2001, Abstract = {Active caspase-3 immunoreactivity was detected in the rat forebrain proliferative regions at birth and remained high in these areas for about 2 weeks, during which period labeled cells were present centroperipherally across the olfactory bulb. By the end of the third postnatal week, only a small number of immunolabeled cells remained in these forebrain structures. Active caspase-3 immunolabeling was localized mostly to cell nuclei and co-localized partially with TuJ1 and NeuN immunoreactivity, but not with glial fibrially acidic protein, OX-42, gamma-aminobutyric acid, or terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL)-positive labeling. Active caspase-3 and 5-bromo-2'-deoxyuridine (BrdU) double-labeled nuclei were seen in the proliferative regions after 2 hours and in the periglomerular region of the bulb after 7 days following BrdU injections. Examination of the cells with electron microscopy confirmed that the active caspase-3-containing nuclei in the proliferative regions often had infoldings and appeared to be undergoing division. Some of the cells with active caspase-3-labeled nuclei in the bulb had synapses on their somata or dendrites. Labeled dendritic spines and a few axon terminals were also observed in the olfactory bulb. Taken together, it appears that a wave of active caspase-3-positive cells are dividing in the proliferative zones and then migrating to the bulb as they differentiate into neurons. Therefore, active caspase-3 may play a role in cellular processes such as neuronal differentiation, migration, and plasticity, in addition to its role in cell death. Copyright 2001 Wiley-Liss, Inc.}, Author = {Yan, X. X. and Najbauer, J. and Woo, C. C. and Dashtipour, K. and Ribak, C. E. and Leon, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Comp Neurol}, Keywords = {Rats, Wistar/*metabolism;Olfactory Bulb/*cytology/growth &development;Rats;Stem Cells/enzymology/ultrastructure;Animal;Immunophenotyping;Male;Antibodies;Antimetabolites;Caspases/analysis/immunology/*metabolism;Cell Division/physiology;In Situ Nick-End Labeling;C;04 Adult neurogenesis factors;Mitosis/*physiology;Support, U.S. Gov't, P.H.S.;Microscopy, Electron;Bromodeoxyuridine;Neurons/*enzymology/ultrastructure}, Number = {1}, Organization = {Department of Neurobiology and Behavior, University of California at Irvine, Irvine, CA 92697, USA.}, Pages = {4-22.}, Title = {Expression of active caspase-3 in mitotic and postmitotic cells of the rat forebrain}, Uuid = {05195B70-E485-49C5-9536-7C18FAE42127}, Volume = {433}, Year = {2001}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11283945}} @article{Yang:2000, Abstract = {PURPOSE: Epileptogenesis is a hallmark of severe cortical trauma, with up to approximately 80\%of patients experiencing seizures in the first 24 hours after penetrating head injury. An in vitro model of traumatic brain injury was developed to investigate hyperexcitability and epileptogenesis and their prevention. We determined whether sodium valproate would prevent epileptiform activity in this experimental model. METHODS: Rat cortical slices were prepared and maintained in vitro using standard methods. Trauma was effected by removing the superficial 450-500 microm of slices. Traumatized slices were exposed to valproate at various time points. Intracellular and extracellular recordings were used to assess evoked activities. RESULTS: In untreated traumatized deep segments, hyperexcitability was manifested by depressed inhibition and often (54\%) by epileptiform activity. Preparations exposed to valproate at 30 minutes or later after trauma showed abnormal activity similar to control traumatized slices. Epileptogenicity in deep segments was significantly reduced when slices were exposed to valproate (a) continuously immediately after trauma, (b) after a 20-minute delay, or (c) immediately after trauma for 1 hour and then returned to physiological solution. Finally, slices that were exposed to valproate or pentobarbital beginning 20 minutes after trauma for only 1 hour and then returned to physiological medium showed a significant reduction in abnormal activity. Valproate was found to enhance fast gamma-aminobutyric acid(A)-ergic inhibitory strength. CONCLUSIONS: Valproate significantly reduces epileptiform activity after trauma to the neocortex, likely by restoring the excitation-inhibition balance, perhaps through augmentation of gamma-aminobutyric acid transmission. The timing of this action may have implications for mechanisms of seizure genesis and may suggest a role for rapid treatment.}, Author = {Yang, L. and Benardo, L. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {gamma-Aminobutyric Acid;Animals;In Vitro;Humans;Rats;Synaptic Transmission;Valproic Acid;Neocortex;Epilepsy;Rats, Sprague-Dawley;21 Epilepsy;Disease Models, Animal;Brain Injuries;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Somatosensory Cortex;24 Pubmed search results 2008;Neural Inhibition;Anticonvulsants}, Medline = {20565485}, Month = {12}, Nlm_Id = {2983306R}, Number = {12}, Organization = {Department of Physiology and Pharmacology, State University of New York Downstate Medical Center, Brooklyn, New York 11203, USA.}, Pages = {1507-13}, Pubmed = {11114207}, Title = {Valproate prevents epileptiform activity after trauma in an in vitro model in neocortical slices}, Uuid = {9F1C6305-BAD4-4B64-9135-B79F5D242671}, Volume = {41}, Year = {2000}} @article{Yang:2001, Abstract = {Alzheimer's disease (AD) is a devastating dementia of late life that is correlated with a region-specific neuronal cell loss. Despite progress in uncovering many of the factors that contribute to the etiology of the disease, the cause of the nerve cell death remains unknown. One promising theory is that the neurons degenerate because they reenter a lethal cell cycle. This theory receives support from immunocytochemical evidence for the reexpression of several cell cycle-related proteins. Direct proof for DNA replication, however, has been lacking. We report here the use of fluorescent in situ hybridization to examine the chromosomal complement of interphase neuronal nuclei in the adult human brain. We demonstrate that a significant fraction of the hippocampal pyramidal and basal forebrain neurons in AD have fully or partially replicated four separate genetic loci on three different chromosomes. Cells in unaffected regions of the AD brain or in the hippocampus of nondemented age-matched controls show no such anomalies. We conclude that the AD neurons complete a nearly full S phase, but because mitosis is not initiated, the cells remain tetraploid. Quantitative analysis indicates that the genetic imbalance persists for many months before the cells die, and we propose that this imbalance is the direct cause of the neuronal loss in Alzheimer's disease. 1529-2401 Journal Article}, Author = {Yang, Y. and Geldmacher, D. S. and Herrup, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Neurosci}, Keywords = {Chromosomes;Human;In Situ Hybridization, Fluorescence;Alzheimer Disease/*etiology/*metabolism/pathology;Cyclin B/metabolism;Hippocampus/metabolism/pathology;Cell Nucleus/metabolism/pathology;*DNA Replication;Interphase;Neurons/*metabolism/pathology;Female;EE pdf;Basal Nucleus of Meynert/metabolism/pathology;Male;Aged;Support, Non-U.S. Gov't;Aged, 80 and over;Support, U.S. Gov't, P.H.S.;Polyploidy;Pyramidal Cells/metabolism/pathology;S Phase;Immunohistochemistry;Prosencephalon/metabolism/pathology;Cell Death;Proliferating Cell Nuclear Antigen/metabolism}, Number = {8}, Organization = {University Alzheimer Center, Department of Neuroscience, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.}, Pages = {2661-8}, Pubmed = {11306619}, Title = {DNA replication precedes neuronal cell death in Alzheimer's disease}, Uuid = {32528674-D395-11D9-A0E9-000D9346EC2A}, Volume = {21}, Year = {2001}, url = {papers/Yang_JNeurosci2001.pdf}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11306619}} @article{Yang:2003, Abstract = {Recent studies based predominantly on nucleotide hybridization techniques have identified aneuploid neurons and glia in the normal brain. To substantiate these findings and address how neural aneuploidy arises, we examined individual neural progenitor cells (NPCs) undergoing mitosis. Here we report the identification of chromosomal segregation defects in normal NPCs of the mouse cerebral cortex. Immunofluorescence in fixed tissue sections revealed the presence of supernumerary centrosomes and lagging chromosomes among mitotic NPCs. The extent of aneuploidy followed the prevalence of supernumerary centrosomes within distinct cell populations. Real-time imaging of live NPCs revealed lagging chromosomes and multipolar divisions. NPCs undergoing nondisjunction were also observed, along with interphase cells that harbored micronuclei or multiple nuclei, consistent with unbalanced nuclear division. These data independently confirm the presence of aneuploid NPCs and demonstrate the occurrence of mitotic segregation defects in normal cells that can mechanistically account for aneuploidy in the CNS. 1529-2401 Journal Article}, Author = {Yang, A. H. and Kaushal, D. and Rehen, S. K. and Kriedt, K. and Kingsbury, M. A. and McConnell, M. J. and Chun, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {J Neurosci}, Keywords = {Karyotyping;EE pdf;Nondisjunction, Genetic;Chromosomes/genetics;*Aneuploidy;Female;08 Aberrant cell cycle;Metaphase/physiology;Mice, Inbred BALB C/genetics;Support, U.S. Gov't, P.H.S.;Mitosis;Chromosome Segregation/*physiology;Support, Non-U.S. Gov't;Animals;Neurons/*cytology/ultrastructure;Stem Cells/*cytology/*metabolism;Mice}, Number = {32}, Organization = {Biomedical Sciences, School of Medicine, University of California, San Diego, California 92093, USA.}, Pages = {10454-62}, Title = {Chromosome segregation defects contribute to aneuploidy in normal neural progenitor cells}, Uuid = {0387BBB2-8F56-493C-9584-18F11020AAD2}, Volume = {23}, Year = {2003}, url = {papers/Yang_JNeurosci2003.pdf}} @article{Yang:2003a, Abstract = {Cell cycle events play a major role in the loss of neurons in advanced Alzheimer's disease (AD). It is currently unknown, however, whether the same is true for the neuronal losses in early disease stages. To explore this issue we analyzed brain autopsy material from individuals clinically categorized with mild cognitive impairment (MCI), many if not most of whom will progress to AD. Immunocytochemistry for three cell cycle-related proteins, proliferating cell nuclear antigen, cyclin D, and cyclin B, was performed on sections from hippocampus, basal nucleus of Meynert, and entorhinal cortex. The results obtained from MCI cases were compared with material from individuals diagnosed with AD and those without cognitive impairment. In both hippocampus and basal nucleus, there was a significant percentage of cell cycle immunopositive neurons in the MCI cases. These percentages were similar to those found in the AD cases but significantly higher than non-cognitively impaired controls. In entorhinal cortex, the density of cell cycle-positive neurons was greater in MCI than in AD. However, we observed large variations in the percentages of immunopositive neurons from individual to individual. These findings lend support to the hypothesis that both the mechanism of cell loss (a cell cycle-induced death) and the rate of cell loss (a slow atrophy over several months) are identical at all stages of the AD disease process. The implication of the findings for human clinical trials is discussed. 1529-2401 Journal Article}, Author = {Yang, Y. and Mufson, E. J. and Herrup, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {J Neurosci}, Keywords = {Human;Disease Progression;Neurons/chemistry/*pathology;Basal Nucleus of Meynert/chemistry/pathology;Cell Cycle;Entorhinal Cortex/chemistry/pathology;Female;Cell Count;EE pdf;Hippocampus/chemistry/pathology;08 Aberrant cell cycle;Male;Aged;Cyclins/analysis/immunology;Cognition Disorders/diagnosis/pathology;Proliferating Cell Nuclear Antigen/analysis/immunology;Support, U.S. Gov't, P.H.S.;Alzheimer Disease/diagnosis/metabolism/*pathology;Immunohistochemistry;Cyclin B/analysis/immunology;Cell Death}, Number = {7}, Organization = {Alzheimer Research Laboratory, University Hospitals of Cleveland and Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA. yxy33\@po.cwru.edu}, Pages = {2557-63}, Pubmed = {12684440}, Title = {Neuronal cell death is preceded by cell cycle events at all stages of Alzheimer's disease}, Uuid = {B12B6DA0-B177-4D7A-A670-ABED3745017D}, Volume = {23}, Year = {2003}, url = {papers/Yang_JNeurosci2003a.pdf}} @article{Yang:2005a, Abstract = {In ataxia-telangiectasia (A-T), the loss of the ataxia-telangiectasia mutated (ATM) kinase leads to a failure of cell cycle checkpoints and DNA double-strand break detection resulting in cellular radiation sensitivity and a predisposition to cancer. There is also a significant loss of neurons, in particular cerebellar granule and Purkinje cells. Mice homozygous for null alleles of atm reproduce the radiation sensitivity and high-tumor incidence of the human disease but show no significant nerve cell loss. Using immunocytochemistry, we found the re-expression of cell cycle proteins in Purkinje cells and striatal neurons in both human and mouse A-T. In the mouse, we used fluorescent in situ hybridization (FISH) to document that DNA replication accompanies the reappearance of these proteins in at-risk neuronal cells. We also found the presence of significant cell cycle activity in the Purkinje cells of the atm+/- heterozygote mouse. The cell cycle events in mouse cerebellum occur primarily during the third postnatal week by both FISH and immunocytochemistry. Thus, the initiation of this ectopic cell division occurs just as the final stages of Purkinje cell development are being completed. These results suggest that loss of cell cycle control represents a common disease mechanism that underlies the defects in the affected tissues in both human and mouse diseases.}, Author = {Yang, Yan and Herrup, Karl}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {08 Aberrant cell cycle}, Month = {3}, Nlm_Id = {8102140}, Number = {10}, Organization = {Department of Neurology, Alzheimer Research Laboratory (E504), Case School of Medicine, Cleveland, Ohio 44106, USA. yan.yang\@case.edu}, Pages = {2522-9}, Pii = {25/10/2522}, Pubmed = {15758161}, Title = {Loss of neuronal cell cycle control in ataxia-telangiectasia: a unified disease mechanism}, Uuid = {E3C78D53-F309-48E6-BA22-B7D932D45784}, Volume = {25}, Year = {2005}, url = {papers/Yang_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4946-04.2005}} @article{Yang:2006c, Abstract = {NG2 cells (polydendrocytes) comprise an abundant glial population that is widely and uniformly distributed throughout the developing and mature CNS and are identified by the expression of the NG2 proteoglycan at the cell surface. Although recent electrophysiological studies suggest that they are capable of receiving signals from axon terminals, other studies, based on the finding that the NG2 molecule itself induces growth cone collapse, have led to a widely held speculation that NG2 cells themselves also repel and inhibit growing axons. In this study, we have examined the effects of rat NG2 cells on growing hippocampal and neocortical axons in vitro and in vivo. NG2 cells did not repel growing axons but promoted their growth in vitro, and axonal growth cones formed extensive contacts with NG2 cells both in vitro and in the developing corpus callosum. Punctate immunoreactivity for fibronectin and laminin was found to be colocalized with NG2 on the surface of NG2 cells. Altering the level of cell surface NG2 expression had no effect on the growth-promoting effects of NG2 cells on growing axons. Thus, our study indicates that NG2 cells are not inhibitory to growing axons but provide an adhesive substrate for axonal growth cones and promote their growth even in the presence of elevated levels of the NG2 proteoglycan. These findings suggest a novel role for NG2 cells in facilitating axonal growth during development and regeneration.}, Author = {Yang, Zhongshu and Suzuki, Ryusuke and Daniels, Stephen B. and Brunquell, Christopher B. and Sala, Christopher J. and Nishiyama, Akiko}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {14}, Organization = {Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut 06269-3156, USA.}, Pages = {3829-39}, Pii = {26/14/3829}, Pubmed = {16597737}, Title = {NG2 glial cells provide a favorable substrate for growing axons}, Uuid = {5489D66D-EF4A-4A0F-983C-44CB369E6DCA}, Volume = {26}, Year = {2006}, url = {papers/Yang_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4247-05.2006}} @article{Yang:2006, Abstract = {Neurogenesis has been described in various regions of the CNS throughout life. We examined the extent of natural cell division and replacement from 7 weeks to 7 months after cervical spinal cord injury in four adult rhesus monkeys. Bromodeoxyuridine (BrdU) injections revealed an increase of >80-fold in the number of newly divided cells in the primate spinal cord after injury, with an average of 725,000 BrdU-labeled cells identified per monkey in the immediate injury zone. By 7 months after injury, 15\%of these new cells expressed mature markers of oligodendrocytes and 12\%expressed mature astrocytic markers. Newly born oligodendrocytes were present in zones of injury-induced demyelination and appeared to ensheath or remyelinate host axons. Thus, cell replacement is an extensive natural compensatory response to injury in the primate spinal cord that contributes to neural repair and is a potential target for therapeutic enhancement.}, Author = {Yang, Hong and Lu, Paul and McKay, Heather M. and Bernot, Tim and Keirstead, Hans and Steward, Oswald and Gage, Fred H. and Edgerton, V. Reggie and Tuszynski, Mark H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cell Differentiation;Research Support, Non-U.S. Gov't;Spinal Cord Injuries;Macaca mulatta;Neuronal Plasticity;Cell Proliferation;Astrocytes;Cell Division;Nerve Regeneration;Research Support, N.I.H., Extramural;Spinal Cord;Animals;Oligodendroglia;24 Pubmed search results 2008;Male;Neurons}, Month = {2}, Nlm_Id = {8102140}, Number = {8}, Organization = {Department of Neurosciences, University of California, San Diego, La Jolla, California 92093-0626, USA.}, Pages = {2157-66}, Pii = {26/8/2157}, Pubmed = {16495442}, Title = {Endogenous neurogenesis replaces oligodendrocytes and astrocytes after primate spinal cord injury}, Uuid = {A13CC3CF-4414-4A2E-A7BE-D97F9FB78BFF}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4070-05.2005}} @article{Yang:2004, Abstract = {Doublecortin (Dcx) is a microtubule-associated protein expressed by migrating neuroblasts in the embryo and in the adult subventricular zone (SVZ). The adult SVZ contains neuroblasts that migrate in the rostral migratory stream (RMS) to the olfactory bulbs. We have examined the distribution and phenotype of Dcx-positive cells in the adult mouse SVZ and surrounding regions. Chains of Dcx-positive cells in the SVZ were distributed in a tight dorsal population contiguous with the RMS, with a separate ventral population comprised of discontinuous chains. Unexpectedly, Dcx-positive cells were also found outside of the SVZ: dorsally in the corpus callosum, and ventrally in the nucleus accumbens, ventromedial striatum, ventrolateral septum, and bed nucleus of the stria terminalis. Dcx-positive cells outside the SVZ had the morphology of migrating cells, occurred as individual cells or in chain-like clusters, and were more numerous anteriorly. Of the Dcx-positive cells found outside of the SVZ, 47\%expressed the immature neuronal protein class III beta-tubulin, 8\%expressed NeuN, a marker of mature neurons. Dcx-positive cells did not express molecules found in astrocytes, oligodendrocytes, or microglia. Structural and immunoelectron microscopy revealed that cells with the ultrastructural features of neuroblasts in the SVZ were Dcx+, and that clusters of neuroblasts emanated ventrally from the SVZ into the parenchyma. Our results suggest that the distribution of cells comprising the walls of the lateral ventricle are more heterogeneous than was thought previously, that SVZ cells may migrate dorsally and ventrally away from the SVZ, and that some emigrated cells express a neuronal phenotype.}, Author = {Yang, Helen K. C. and Sundholm-Peters, Nikki L. and Goings, Gwendolyn E. and Walker, Avery S. and Hyland, Kenneth and Szele, Francis G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Mice;Nucleus Accumbens;02 Adult neurogenesis migration;Tissue Distribution;Female;Immunohistochemistry;Stem Cells;Neuropeptides;Lateral Ventricles;Support, U.S. Gov't, P.H.S.;Male;Cell Movement;Animals;Neurons;Microtubule-Associated Proteins}, Month = {5}, Nlm_Id = {7600111}, Number = {3}, Organization = {Children's Memorial Hospital, Department of Pediatrics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60614-3394, USA.}, Pages = {282-95}, Pubmed = {15079857}, Title = {Distribution of doublecortin expressing cells near the lateral ventricles in the adult mouse brain}, Uuid = {2DDD1439-B38A-41FB-A5E9-B8E56C2DCB0B}, Volume = {76}, Year = {2004}, url = {papers/Yang_JNeurosciRes2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.20071}} @article{Yang:2006b, Abstract = {Neurons and oligodendrocyte progenitors are highly sensitive to perinatal hypoxic-ischemic injury. As accumulating evidence suggests that many insults to the human infant occur in utero, and preventing brain damage to infants in utero will prove difficult, there is strong rationale to pursue regenerative strategies to reduce the morbidity associated with developmental brain injuries. The purpose of this study was to determine whether a hypoxic-ischemic insult stimulates the neural stem/progenitor cells in the subventricular zone to generate new neurons and oligodendrocytes. Hypoxia-ischemia was induced using the Vannucci rat model on postnatal day-6 pups. Injections of 5'-bromo-2'-deoxyuridine to label cells undergoing DNA synthesis after hypoxia-ischemia revealed that there is a robust proliferative response within the subventricular zone of the injured hemisphere that continues for at least 1 week after the hypoxic-ischemic episode. Using the neurosphere assay to quantify the number of neural stem/progenitor cells in the subventricular zone, we find that there are twice as many neural stem/progenitor cells in the affected dorsolateral subventricular zone at 1 week of recovery and that these cells generate larger spheres in response to growth factors compared with controls. Precursors from the injured hemisphere generate three times as many neurons in vitro and more than twice as many oligodendroglia compared with controls. Hypoxia-ischemia also increases neurogenesis in vivo. Doublecortin positive cells with migratory profiles were observed streaming from the ipsilateral subventricular zone to the striatum and neocortex, whereas, few doublecortin positive cells were found in the contralateral hemisphere after hypoxia-ischemia. These observations provide evidence that the somatic neural progenitors of the subventricular zone participate in the production of new brain cells lost after hypoxia-ischemia.}, Author = {Yang, Z. and Levison, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {24 Pubmed search results 2008}, Nlm_Id = {7605074}, Number = {2}, Organization = {Department of Neurology and Neurosciences, UMDNJ-New Jersey Medical School, Newark, NJ 07101, USA.}, Pages = {555-64}, Pii = {S0306-4522(06)00043-1}, Pubmed = {16500031}, Title = {Hypoxia/ischemia expands the regenerative capacity of progenitors in the perinatal subventricular zone}, Uuid = {7D715258-2FED-4F77-A87D-30A23CA23B7E}, Volume = {139}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2005.12.059}} @article{Yang:2000a, Abstract = {Spinal cord neuronal restricted progenitor (NRP) cells, when transplanted into the neonatal anterior forebrain subventricular zone, migrate to distinct regions throughout the forebrain including the olfactory bulb, frontal cortex, and occipital cortex but not to the hippocampus. Their migration pattern and differentiation potential is distinct from anterior forebrain subventricular zone NRPs. Irrespective of their final destination, NRP cells do not differentiate into glia. Rather they synthesize neurotransmitters, acquire region-specific phenotypes, and receive synapses from host neurons after transplantation. Spinal cord NRPs express choline acetyl transferase even in regions where host neurons do not express this marker. The restricted distribution of transplanted spinal cord NRP cells and their acquisition of varied region-specific phenotypes suggest that their ultimate fate and phenotype is dictated by a combination of intrinsic properties and extrinsic cues from the host. 0027-8424 Journal Article}, Author = {Yang, H. and Mujtaba, T. and Venkatraman, G. and Wu, Y. Y. and Rao, M. S. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Olfactory Nerve/*physiology;Cell Differentiation;Animals;Olfactory Bulb/*physiology;10 Development;Neurons/*cytology/physiology;Transfection;Rats;Synapses/*physiology;Glutamic Acid/analysis;Cell Movement;Brain/cytology/*physiology;Prosencephalon/cytology/physiology;Time Factors;Synaptophysin/analysis;*Cell Transplantation;Choline O-Acetyltransferase/analysis;Luminescent Proteins/analysis/genetics;Animals, Newborn;gamma-Aminobutyric Acid/analysis;Stem Cells/*cytology/physiology;Genes, Reporter;Biological Markers;F;Nerve Tissue Proteins/*analysis;Spinal Cord/*cytology}, Number = {24}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.}, Pages = {13366-71}, Pubmed = {11087876}, Title = {Region-specific differentiation of neural tube-derived neuronal restricted progenitor cells after heterotopic transplantation}, Uuid = {324EAEFA-BC4E-44F2-9D82-D18EB50F37E5}, Volume = {97}, Year = {2000}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11087876}} @article{Yang:2006a, Abstract = {We have developed an efficient method to target lentivirus-mediated gene transduction to a desired cell type. It involves incorporation of antibody and fusogenic protein as two distinct molecules into the lentiviral surface. The fusogen is constructed by modifying viral envelope proteins, so that they lack the ability to bind to their cognate receptor but still retain the ability to trigger pH-dependent membrane fusion. Thus, the specificity of such a lentiviral vector is solely determined by the antibody, which is chosen to recognize a specific surface antigen of the desired cell type. This specific binding then induces endocytosis of the surface antigen, bringing the lentivirus into an endosome. There, the fusogen responds to the low pH environment and mediates membrane fusion, allowing the virus core to enter the cytosol. Using CD20 as a target antigen for human B cells, we have demonstrated that this targeting strategy is effective both in vitro and in intact animals. This methodology is flexible and can be extended to other forms of cell type-specific recognition to mediate targeting. The only requirement is that the antibody (or other binding protein) must be endocytosed after interaction with its cell surface-binding determinant.}, Author = {Yang, Lili and Bailey, Leslie and Baltimore, David and Wang, Pin}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Transduction, Genetic;Animals;Humans;Lentivirus;Female;15 Retrovirus mechanism;23 Technique;Hydrogen-Ion Concentration;B-Lymphocytes;Recombinant Fusion Proteins;Genetic Vectors;Viral Envelope Proteins;research support, non-u.s. gov't ;Cell Line;Antibodies;Mice, Knockout;Membrane Fusion;Mice;24 Pubmed search results 2008;Antigens, CD20}, Month = {8}, Nlm_Id = {7505876}, Number = {31}, Organization = {Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.}, Pages = {11479-84}, Pii = {0604993103}, Pubmed = {16864770}, Title = {Targeting lentiviral vectors to specific cell types in vivo}, Uuid = {583840C9-A941-4998-93C4-3CD64F3C764D}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0604993103}} @article{Yang:2005, Abstract = {OBJECTIVES: To investigate the mRNA and protein expression of SMN gene in neuron-like cells by inducing MSC to differentiate into neuron-like cells. METHODS: Human MSC (hMSC) were isolated and purified. Human MSC were treated with basic fibroblast growth factor (bFGF) before inducing hMSC to differentiate into neuron-like cells with dimethylsulfoxide (DMSO) and butylated hydroxyanisole (BHA). The expression of NSE, NF, and SMN protein in neuron-like cells were detected by immunohistochemistry. The expression of SMN mRNA were detected with reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Human MSC progressively assumed neuronal morphological characteristics after being induced for 3 hours. Cell bodies had long processe contacting with each other. The neuronal marker of NSE and NF was positive in neuron-like cells. Both hMSC and neuron-like cells expressed the mRNA of SMN gene. Compared with hMSC the latter expressed highly the mRNA of SMN gene and it was significance (P < 0.01). SMN protein was only expressed in neuron-like cells. CONCLUSIONS: Human MSC are able to differentiate into neuron-like cells with expressing the neuronal marker. Neuron-like cells can express highly the mRNA of SMN gene and express SMN protein.}, Author = {Yang, Xiao-Su S. and Wu, Hai-Xiang X. and Xiao, Bo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0376-2491}, Journal = {Zhonghua Yi Xue Za Zhi}, Keywords = {11 Glia}, Month = {4}, Nlm_Id = {7511141}, Notes = {cell fusion, dendrite fusing to microglia or macrophages}, Number = {16}, Organization = {Department of Neurology, XiangYa Hospital of Centersouth University. Changsha 410008, China. Email: yanxia\@public.cs.hn.cn.}, Pages = {1125-8}, Pubmed = {16029573}, Title = {[Human mesenchymal stem cells differentiat into neuron-like cells and show SMN protein expression.]}, Uuid = {4B9391B4-9A09-4018-BF3A-C496BAEA4AF8}, Volume = {85}, Year = {2005}} @article{Yao:2003, Abstract = {The fusogenic envelope glycoprotein G of the rhabdovirus vesicular stomatitis virus (VSV) induces membrane fusion at acidic pH. At acidic pH the G protein undergoes a major structural reorganization leading to the fusogenic conformation. However, unlike other viral fusion proteins, the low-pH-induced conformational change of VSV G is completely reversible. As well, the presence of an alpha-helical coiled-coil motif required for fusion by a number of viral and cellular fusion proteins was not predicted in VSV G protein by using a number of algorithms. Results of pH dependence of the thermal stability of G protein as determined by intrinsic Trp fluorescence and circular dichroism (CD) spectroscopy show that the G protein is equally stable at neutral or acidic pH. Destabilization of G structure at neutral pH with either heat or urea did not induce membrane fusion or conformational change(s) leading to membrane fusion. Taken together, these data suggest that the mechanism of VSV G-induced fusion is distinct from the fusion mechanism of fusion proteins that involve a coiled-coil motif.}, Author = {Yao, Yi and Ghosh, Kakoli and Epand, Raquel F. and Epand, Richard M. and Ghosh, Hara P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0042-6822}, Journal = {Virology}, Keywords = {Membrane Glycoproteins;Research Support, Non-U.S. Gov't;Virus Replication;Membrane Fusion;Cell Line;Time Factors;Urea;Heat;Vesicular stomatitis-Indiana virus;15 Retrovirus mechanism;Animals;Hydrogen-Ion Concentration;24 Pubmed search results 2008;Viral Envelope Proteins}, Medline = {22667914}, Month = {6}, Nlm_Id = {0110674}, Number = {2}, Organization = {Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.}, Pages = {319-32}, Pii = {S0042682203001466}, Pubmed = {12781719}, Title = {Membrane fusion activity of vesicular stomatitis virus glycoprotein G is induced by low pH but not by heat or denaturant}, Uuid = {2F4C41BA-BD48-4F9F-9FEC-55E6D1BC7FF2}, Volume = {310}, Year = {2003}, url = {papers/Yao_Virology2003.pdf}} @article{Yasuhara:2006, Abstract = {Neural stem cells (NSCs) possess high potencies of self-renewal and neuronal differentiation. We explored here whether transplantation of human NSCs cloned by v-myc gene transfer, HB1.F3 cells, is a feasible therapeutic option for Parkinson's disease. In vivo, green fluorescent protein-labeled HB1.F3 cells (200,000 viable cells in 3 microl of PBS) when stereotaxically transplanted (same-day lesion-transplant paradigm) into the 6-hydroxydopamine-lesioned striatum of rats significantly ameliorated parkinsonian behavioral symptoms compared with controls (vehicle, single bolus, or continuous minipump infusion of trophic factor, or killed cell grafts). Such graft-derived functional effects were accompanied by preservation of tyrosine hydroxylase (TH) immunoreactivity along the nigrostriatal pathway. Grafted HB1.F3 cells survived in the lesioned brain with some labeled with neuronal marker mitogen-activated protein 2 and decorated with synaptophysin-positive terminals. Furthermore, endogenous neurogenesis was activated in the subventricular zone of transplanted rats. To further explore the neuroprotective mechanisms underlying HB1.F3 cell transplantation, we performed cell culture studies and found that a modest number of HB1.F3 cells were TH and dopamine and cAMP-regulated phosphoprotein 32 positive, although most cells were nestin positive, suggesting a mixed population of mature and immature cells. Administration of the HB1.F3 supernatant to human derived dopaminergic SH-SY5Y cells and fetal rat ventral mesencephalic dopaminergic neurons protected against 6-hydroxydopamine neurotoxicity by suppressing apoptosis through Bcl-2 upregulation, which was blocked by anti-stem cell factor antibody alone, the phosphatidylinositol 3-kinase/Akt inhibitor LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one] alone, or a combination of both. These results suggest that HB1.F3 cell transplantation exerts neuroprotective effects against dopaminergic depletion in vitro and in vivo because of trophic factor secretion and neuronal differentiation.}, Author = {Yasuhara, Takao and Matsukawa, Noriyuki and Hara, Koichi and Yu, Guolong and Xu, Lin and Maki, Mina and Kim, Seung U. and Borlongan, Cesario V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Brain Tissue Transplantation;research support, non-u.s. gov't;Rats, Sprague-Dawley;Rats;Cell Line;Stem Cells;Corpus Striatum;Parkinson Disease;comparative study;Motor Activity;Animals;Disease Models, Animal;Humans;Stem Cell Transplantation;24 Pubmed search results 2008}, Month = {11}, Nlm_Id = {8102140}, Number = {48}, Organization = {Department of Neurology, Medical College of Georgia, Augusta, Georgia 30912, USA.}, Pages = {12497-511}, Pii = {26/48/12497}, Pubmed = {17135412}, Title = {Transplantation of human neural stem cells exerts neuroprotection in a rat model of Parkinson's disease}, Uuid = {1BF690CB-CB63-4D4F-A942-3A134FBFA55F}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3719-06.2006}} @article{Yates:2002, Abstract = {Patients with mutations of either RAG-1 or RAG-2 genes suffer from severe combined immunodeficiency (SCID) characterized by the lack of T and B lymphocytes. The only curative treatment today consists of hematopoietic stem cell (HSC) transplantation, which is only partially successful in the absence of an HLA genoidentical donor, thus justifying research to find an alternative therapeutic approach. To this end, RAG-2-deficient mice were used to test whether retrovirally mediated ex vivo gene transfer into HSCs could provide long-term correction of the immunologic deficiency. Murine RAG-2-/-Sca-1(+) selected bone marrow cells were transduced with a modified Moloney leukemia virus (MLV)-based MND (myeloproliferative sarcoma virus enhancer, negative control region deleted, dl587rev primer-binding site substituted) retroviral vector containing the RAG-2 cDNA and transplanted into RAG-2-/- sublethally irradiated mice (3Gy). Two months later, T- and B-cell development was achieved in all mice. Diverse repertoire of T cells as well as proliferative capacity in the presence of mitogens, allogeneic cells, and keyhole limpet hemocyanin (KLH) were shown. B-cell function as shown by serum Ig levels and antibody response to a challenge by KLH also developed. Lymphoid subsets and function were shown to be stable over a one-year period without evidence of any detectable toxicity. Noteworthy, a selective advantage for transduced lymphoid cells was evidenced by comparative provirus quantification in lymphoid and myeloid lineages. Altogether, this study demonstrates the efficiency of ex vivo RAG-2 gene transfer in HSCs to correct the immune deficiency of RAG-2-/- mice, constituting a significant step toward clinical application.}, Author = {Yates, Frank and Malassis-S{\'e}ris, Mich\`{e}le and Stockholm, Daniel and Bouneaud, C{\'e}cile and Larousserie, Fr{\'e}d{\'e}rique and Noguiez-Hellin, Patricia and Danos, Olivier and Kohn, Donald B. and Fischer, Alain and de Villartay, Jean-Pierre P. and Cavazzana-Calvo, Marina}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {T-Lymphocytes;Transduction, Genetic;Animals;DNA-Binding Proteins;Bone Marrow Transplantation;Severe Combined Immunodeficiency;Female;Mice, Inbred C3H;B-Lymphocytes;Mice, Inbred C57BL;Retroviridae;11 Glia;Male;Bone Marrow Cells;Cell Lineage;Gene Therapy;Mice, Knockout;Mice;Virus Integration;Receptors, Antigen, T-Cell;Cell Division;Research Support, Non-U.S. Gov't}, Medline = {22320963}, Month = {12}, Nlm_Id = {7603509}, Number = {12}, Organization = {Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM) U429, H\^{o}pital Necker-Enfants Malades, Paris, France.}, Pages = {3942-9}, Pii = {2002-03-0782}, Pubmed = {12393742}, Title = {Gene therapy of RAG-2-/- mice: sustained correction of the immunodeficiency}, Uuid = {44BDBB6C-0836-4B39-9102-BE8918211341}, Volume = {100}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1182/blood-2002-03-0782}} @article{Ye:2007, Abstract = {Little is known about how the distinct architectures of dendrites and axons are established. From a genetic screen, we isolated dendritic arbor reduction (dar) mutants with reduced dendritic arbors but normal axons of Drosophila neurons. We identified dar2, dar3, and dar6 genes as the homologs of Sec23, Sar1, and Rab1 of the secretory pathway. In both Drosophila and rodent neurons, defects in Sar1 expression preferentially affected dendritic growth, revealing evolutionarily conserved difference between dendritic and axonal development in the sensitivity to limiting membrane supply from the secretory pathway. Whereas limiting ER-to-Golgi transport resulted in decreased membrane supply from soma to dendrites, membrane supply to axons remained sustained. We also show that dendritic growth is contributed by Golgi outposts, which are found predominantly in dendrites. The distinct dependence between dendritic and axonal growth on the secretory pathway helps to establish different morphology of dendrites and axons.}, Author = {Ye, Bing and Zhang, Ye and Song, Wei and Younger, Susan H. and Jan, Lily Yeh and Jan, Yuh Nung}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Golgi Apparatus;Exocytosis;Animals;Cells, Cultured;comparative study;Transfection;Neural Pathways;Cell Membrane;Mutation;Hippocampus;Cell Polarity;RNA, Small Interfering;research support, non-u.s. gov't;Axons;Dendrites;Fluorescence Recovery After Photobleaching;Neurons;Drosophila;research support, n.i.h., extramural;24 Pubmed search results 2008;Embryo, Nonmammalian}, Month = {8}, Nlm_Id = {0413066}, Number = {4}, Organization = {Howard Hughes Medical Institute, Department of Physiology, University of California, San Francisco, CA 94143, USA.}, Pages = {717-29}, Pii = {S0092-8674(07)00836-7}, Pubmed = {17719548}, Title = {Growing dendrites and axons differ in their reliance on the secretory pathway}, Uuid = {73401A63-36CF-4CFD-956F-3E097D7A06ED}, Volume = {130}, Year = {2007}, url = {papers/Ye_Cell2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2007.06.032}} @article{Yee:2003, Abstract = {This paper analyzes the effects of a convulsant and an anticonvulsant manipulation on spontaneous bursts in CA3 pyramidal cells in the in vitro slice preparation under conditions of low (3.3 mM [K(+)](o)) and high (8.5 mM [K(+)](o)) burst probability. When burst probability was low, the anticonvulsant, pentobarbital, produced the anticipated effects: the burst duration decreased and interburst interval increased. However, when burst probability was high, both anticonvulsant and convulsant manipulations decreased the interburst interval and the burst duration. To reconcile these findings, we utilized a model in which CA3 burst duration is limited by activity-dependent depression of CA3 excitatory recurrent collateral synapses and the interburst interval is determined by the time required to recover from this depression. We defined the burst end threshold as the level of synaptic depression at which bursts terminate, and the burst start threshold as the level of synaptic depression at which burst initiation is possible. Synapses were considered to oscillate between these thresholds. When average burst duration and interburst interval data were fit using this model, the paradoxically similar effects of the convulsant and anticonvulsant manipulations could be quantitatively interpreted. The convulsant maneuver decreased both the burst start and end thresholds. The start threshold decreased more than the end threshold, so that the thresholds were closer together. This decreased the time needed to transition from one threshold to the other, i.e., the interburst interval and burst duration. The anticonvulsant manipulation primarily increased the burst end threshold. This also decreased the difference between thresholds, decreasing both interburst interval and burst duration. This model resolves the paradoxical proconvulsant effects of pentobarbital in the CA3 preparation and provides insights into the effects of anticonvulsants on epileptiform discharges in the human EEG.}, Author = {Yee, Audrey S. and Longacher, J. Mark and Staley, Kevin J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0022-3077}, Journal = {J Neurophysiol}, Keywords = {Animals;Rats;Pentobarbital;Acetazolamide;research support, u.s. gov't, p.h.s. ;Epilepsy;Hippocampus;Pyramidal Cells;Rats, Wistar;Organ Culture Techniques;research support, non-u.s. gov't ;Action Potentials;21 Neurophysiology;Picrotoxin;Convulsants;24 Pubmed search results 2008;Models, Neurological;Anticonvulsants}, Month = {1}, Nlm_Id = {0375404}, Number = {1}, Organization = {Department of Pediatrics, B 182, University of Colorado Health Sciences Center, Denver 80262, USA.}, Pages = {427-41}, Pubmed = {12522191}, Title = {Convulsant and anticonvulsant effects on spontaneous CA3 population bursts}, Uuid = {A49C6CEA-FBA4-4431-93F7-56B72AB06712}, Volume = {89}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1152/jn.00594.2002}} @article{Yeung:1997, Abstract = {Tuberous sclerosis (TSC) is an autosomal dominant syndrome that is linked to two genetic loci: TSC1 (9q34) and TSC2 (16p13). Brain manifestations such as cortical tubers and subependymal hamartoma/giant cell astrocytomas are major causes of TSC-related morbidity. In this study, we describe the central nervous system involvement in a unique rodent model of tuberous sclerosis. The Eker rat carries a spontaneous germline mutation of the TSC2 gene and is predisposed to multiple neoplasia. In a series of 45 adult Eker carriers (TSC2 +/-), three types of focal intracranial lesions were found, of which the subependymal and subcortical hamartomas were most prevalent (65\%). There exist remarkable phenotypic similarities between the Eker rat and human subependymal lesions. Our study indicates that the predominant cellular phenotype of the subependymal hamartomas is astroglial and suggests that the neuronal contribution within these lesions is, in part, the result of pre-existing myelinated axons. The hamartomas did not show evidence of loss of the wild-type TSC2 allele; it remains to be determined whether TSC2 inactivation is necessary for their pathogenesis. This genetically-defined rodent model may be useful in elucidating the molecular and developmental basis of the subependymal giant cell astrocytoma in humans.}, Author = {Yeung, R. S. and Katsetos, C. D. and Klein-Szanto, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0002-9440}, Journal = {Am J Pathol}, Keywords = {10 Development;Animals;Astrocytes;Rats;Myelin Basic Proteins;Tubulin;Hamartoma;Tuberous Sclerosis;Rodent Diseases;Neurofilament Proteins;research support, non-u.s. gov't;Brain Diseases;Calcium-Binding Protein, Vitamin D-Dependent;Disease Models, Animal;Rats, Inbred F344;10 genetics malformation;research support, u.s. gov't, p.h.s.;Ependyma;Loss of Heterozygosity;24 Pubmed search results 2008;Immunohistochemistry;Glial Fibrillary Acidic Protein}, Month = {11}, Nlm_Id = {0370502}, Number = {5}, Organization = {Division of Medical Sciences, Fox Chase Cancer Center, Philadelphia, Pennsylvania, USA. ryeung\@u.washington.edu}, Pages = {1477-86}, Pubmed = {9358774}, Title = {Subependymal astrocytic hamartomas in the Eker rat model of tuberous sclerosis}, Uuid = {28398DBA-A19A-41E9-AF9C-78592DA9CE3D}, Volume = {151}, Year = {1997}} @article{Yi:2003, Abstract = {Macrophage/microglia cells are the principal targets for human immunodeficiency virus type 1 (HIV-1) in the central nervous system (CNS). Prototype HIV-1 isolates from the CNS are macrophage (M)-tropic, non-syncytia-inducing (NSI), and use CCR5 for entry (R5 strains), but whether syncytia-inducing (SI) CXCR4-using X4 strains might play a role in macrophage/microglia infection and neuronal injury is unknown. To explore the range of features among HIV-1 primary isolates from the CNS, the authors analyzed an HIV-1 strain (TYBE) from cerebrospinal fluid of an individual with acquired immunodeficiency syndrome (AIDS) that was unusual because it was SI. Like other CNS isolates, HIV-1/TYBE replicated to high level in primary human macrophages, but, in contrast to CNS prototypes, TYBE used CXCR4 exclusively to infect macrophages. A functional TYBE env clone confirmed the X4 phenotype and displayed a highly charged V3 sequence typical of X4 strains. Supernatant from TYBE-infected primary human macrophages induced apoptosis of neurons. Thus, TYBE represents a novel type of CNS-derived HIV-1 isolate that is CXCR4-restricted yet replicates efficiently in macrophages and induce neuronal injury. These results demonstrate that HIV-1 variants in the CNS may possess a broader range of biological characteristics than generally appreciated, raise the possibility that X4 strains may participate in AIDS neuropathogenesis, and provide a prototype clade B HIV-1 strain that replicates efficiently in primary macrophages through the exclusive use of CXCR4 as a coreceptor.}, Author = {Yi, Yanjie and Chen, Wei and Frank, Ian and Cutilli, Joann and Singh, Anjali and Starr-Spires, Linda and Sulcove, Jerrold and Kolson, Dennis L. and Collman, Ronald G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {1355-0284}, Journal = {J Neurovirol}, Keywords = {Giant Cells;HIV-1;Molecular Sequence Data;Human;AIDS Dementia Complex;Apoptosis;Research Support, U.S. Gov't, P.H.S.;11 Glia;Amino Acid Sequence;Macrophages;Support, U.S. Gov't, P.H.S.;Humans;Receptors, CXCR4;Viral Envelope Proteins;Neurons}, Medline = {22788971}, Month = {8}, Nlm_Id = {9508123}, Number = {4}, Organization = {Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.}, Pages = {432-41}, Pii = {DENFV4EX0QK78HR5}, Pubmed = {12907388}, Title = {An unusual syncytia-inducing human immunodeficiency virus type 1 primary isolate from the central nervous system that is restricted to CXCR4, replicates efficiently in macrophages, and induces neuronal apoptosis}, Uuid = {917DA5AA-86B9-4800-92AE-A223DC03C9AA}, Volume = {9}, Year = {2003}} @article{Yin:2006, Abstract = {The optic nerve, like most mature CNS pathways, does not regenerate after injury. Through unknown mechanisms, however, macrophage activation in the eye stimulates retinal ganglion cells (RGCs) to regenerate long axons beyond the site of optic nerve injury. Here we identify the calcium (Ca(2+))-binding protein oncomodulin as a potent macrophage-derived growth factor for RGCs and other neurons. Oncomodulin binds to rat RGCs with high affinity in a cyclic AMP (cAMP)-dependent manner and stimulates more extensive outgrowth than other known trophic agents. Depletion of oncomodulin from macrophage-conditioned media (MCM) eliminates the axon-promoting activity of MCM. The effects of oncomodulin involve downstream signaling via Ca(2+)/calmodulin kinase and gene transcription. In vivo, oncomodulin released from microspheres promotes regeneration in the mature rat optic nerve. Oncomodulin also stimulates outgrowth from peripheral sensory neurons. Thus, oncomodulin is a new growth factor for neurons of the mature central and peripheral nervous systems.}, Author = {Yin, Yuqin and Henzl, Michael T. and Lorber, Barbara and Nakazawa, Toru and Thomas, Tommy T. and Jiang, Fan and Langer, Robert and Benowitz, Larry I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {10 Development;11 Glia;10 Structural plasticity;24 Pubmed search results 2008}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {[1] Department of Neurosurgery and Neurobiology Program, Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts 02115, USA. [2] Department of Surgery, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {843-52}, Pii = {nn1701}, Pubmed = {16699509}, Title = {Oncomodulin is a macrophage-derived signal for axon regeneration in retinal ganglion cells}, Uuid = {BD41E2CA-4E98-4F57-8AFD-83A78AA77E90}, Volume = {9}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1701}} @article{Ying:2002, Abstract = {Recent reports have suggested that mammalian stem cells residing in one tissue may have the capacity to produce differentiated cell types for other tissues and organs 1-9. Here we define a mechanism by which progenitor cells of the central nervous system can give rise to non-neural derivatives. Cells taken from mouse brain were co-cultured with pluripotent embryonic stem cells. Following selection for a transgenic marker carried only by the brain cells, undifferentiated stem cells are recovered in which the brain cell genome has undergone epigenetic reprogramming. However, these cells also carry a transgenic marker and chromosomes derived from the embryonic stem cells. Therefore the altered phenotype does not arise by direct conversion of brain to embryonic stem cell but rather through spontaneous generation of hybrid cells. The tetraploid hybrids exhibit full pluripotent character, including multilineage contribution to chimaeras. We propose that transdetermination consequent to cell fusion 10 could underlie many observations otherwise attributed to an intrinsic plasticity of tissue stem cells 9. 0028-0836 Journal Article}, Author = {Ying, Q. L. and Nichols, J. and Evans, E. P. and Smith, A. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Nature}, Keywords = {Drug Resistance/genetics;Animals;Cells, Cultured;Chimera;*Cell Differentiation;Neurons/*cytology;Antigens, Differentiation;Embryo and Fetal Development;EE pdf;Blastocyst/cytology;Female;Mice, Transgenic;Mice, Inbred C57BL;08 Aberrant cell cycle;Male;Embryo/cytology;Stem Cells/*cytology;Cell Line;Support, Non-U.S. Gov't;*Cinnamates;Hygromycin B/*analogs &derivatives/pharmacology;*Cell Fusion;Coculture;Anti-Bacterial Agents/pharmacology;Brain/cytology;Mice;Hybrid Cells/cytology}, Number = {6880}, Organization = {Centre for Genome Research, University of Edinburgh, The King's Buildings, West Mains Road, Edinburgh EH9 3JQ, UK.}, Pages = {545-8}, Title = {Changing potency by spontaneous fusion}, Uuid = {96427206-D3B0-11D9-A0E9-000D9346EC2A}, Volume = {416}, Year = {2002}, url = {papers/Ying_Nature2002.pdf}} @article{Yokoo:2003, Abstract = {BACKGROUND: Bone marrow reconstitution using genetically-modified hematopoietic stem cells has been reported to confer resistance to inflammation and prevent renal injury in glomerulonephritis. Although this strategy has potentials for clinical use, taking hematopoietic stem cells from bone marrow is highly stressful for patients. In this regard, umbilical cord blood may be a useful alternative and, therefore, we focused on their suitability as a source of hematopoietic stem cells for transplantation-based therapy for glomerulonephritis. METHODS: CD34+ cells were obtained from human umbilical cord blood, retrovirally transduced with human beta-glucuronidase (HBG) gene, and transplanted into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. After confirming the successful chimerism, these mice were treated with lipopolysaccharide (LPS), and local HBG expression in glomeruli was examined using immunohistochemical analysis, HBG bioassay, and Western blot analysis. RESULTS: Clonogenic assay showed that 88.4 +/- 5.9\%burst-forming unit-erythroid (BFU-E), 79.7 +/- 11.4\%in colony-forming unit-macrophage (CFU-M), and 81.1 +/- 14.1\%in colony-forming unit-granulocyte (CFU-G), respectively, possessed the transgene after transfection, suggesting that precommited cells were susceptible to retroviral infection. Flow cytometric analysis revealed that 24.1 +/- 14.5\%of bone marrow cells in these chimera mice expressed human lymphocyte antigen (HLA) 8 weeks after transplantation. Also, clonogenic assay showed that a sustained engraftment of human hematopoietic cells expressed HBG. CD14-positive cells were recruited into the glomeruli upon LPS treatment and they secreted bioactive HBG, suggesting that cord blood-derived CD34+cells may differentiate into monocyte lineage while maintaining the expression of the transgene. CONCLUSION: These data indicate that umbilical cord blood cells can be utilized as a source of hematopoietic stem cells for the transplantation-based therapy of glomerulonephritis.}, Author = {Yokoo, Takashi and Ohashi, Toya and Utsunomiya, Yasunori and Okamoto, Aikou and Suzuki, Takahide and Shen, Jin Song and Tanaka, Tadao and Kawamura, Tetsuya and Hosoya, Tatsuo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0085-2538}, Journal = {Kidney Int}, Keywords = {Glucuronidase;Cell Differentiation;Mice, Inbred NOD;Animals;Monocytes;Humans;Blood Cells;Transfection;Glomerulonephritis;Lipopolysaccharides;Mice, SCID;Antigens, CD34;Retroviridae;Transplantation Chimera;11 Glia;Kidney Glomerulus;Genetic Vectors;Hematopoietic Stem Cell Transplantation;Gene Transfer Techniques;Mice;Fetal Blood;Blood Component Transfusion;Research Support, Non-U.S. Gov't}, Medline = {22672614}, Month = {7}, Nlm_Id = {0323470}, Number = {1}, Organization = {Division of Nephrology and Hypertension, Department of Internal Medicine, Institute of DNA Medicine, Jikei University School of Medicine, Tokyo, Japan. tyokoo\@jikei.ac.jp}, Pages = {102-9}, Pii = {kid046}, Pubmed = {12787400}, Title = {Gene delivery using human cord blood-derived CD34+cells into inflamed glomeruli in NOD/SCID mice}, Uuid = {A58CB037-8F74-471F-9338-1531EB08B24C}, Volume = {64}, Year = {2003}} @article{Yokota:1993, Abstract = {The rate of migration of immature granule cells of the rat olfactory bulb and polarity of cell-organelles in the migrating granule cells were investigated by 3H-thymidine autoradiographic and electron microscopic methods. The time lag in migration between two points was determined by cross-correlation analysis of labeling indices of the two areas. Granule cells were estimated to take 6 days to migrate rostralwardly from the subependymal layer at the anterior wall of the lateral ventricle to the center of the bulb, and an additional 1 to 6 days to migrate radially from the subependymal layer to the granular layer of the bulb. These results showed that the rate of rostralward migration of granule cells was faster than that of their radial migration. Golgi-electron microscopic as well as routine electron microscopic studies on migrating granule cells revealed that centrioles and Golgi apparatus were located at the base of the leading process that possesses a growth cone at its tip. eng Journal Article}, Author = {Yokota, S. and Kakuta, S. and Ishikawa, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Journal = {Arch Histol Cytol}, Keywords = {Cell Differentiation;Centrioles/ultrastructure;Rats;Microscopy, Electron;Olfactory Bulb/*cytology/ultrastructure;Thymidine/metabolism;Rats, Wistar;Autoradiography;Animal;*Cell Polarity;I abstr;Golgi Apparatus/ultrastructure;Cell Movement;13 Olfactory bulb anatomy}, Number = {1}, Organization = {Department of Anatomy, Toho University School of Medicine, Tokyo, Japan.}, Pages = {27-36.}, Title = {Development of granule cells of the rat olfactory bulb: an autoradiographic and electron microscopic study}, Uuid = {C4860140-8FD2-4FE9-9927-5721D213BB86}, Volume = {56}, Year = {1993}} @article{Yokota:2004, Abstract = {Radial glial proliferation is a critical step in the construction of cerebral cortex. In this issue of Neuron, Weissman and colleagues use time-lapse calcium imaging techniques to demonstrate that spontaneous calcium waves sweeping through cohorts of radial glia in the ventricular zone can modulate their proliferation during cerebral cortical development.}, Author = {Yokota, Yukako and Anton, E. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cerebral Cortex;Adenosine Triphosphate;Cell Differentiation;Neuroglia;10 Development;Cell Communication;Cell Division;review, tutorial;comment;Calcium Signaling;Animals;Cell Movement;Humans;Neurons;review}, Month = {9}, Nlm_Id = {8809320}, Number = {5}, Organization = {UNC Neuroscience Center, The University of North Carolina School of Medicine, Chapel Hill 27599, USA.}, Pages = {599-601}, Pii = {S0896627304005367}, Pubmed = {15339639}, Title = {Calcium waves rule and divide radial glia}, Uuid = {0BB83AC2-7588-4CE4-A954-A3888B377041}, Volume = {43}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2004.08.030}} @article{Yokota:2007, Abstract = {Interneurons originating from the ganglionic eminence migrate tangentially into the developing cerebral wall as they navigate to their distinct positions in the cerebral cortex. Compromised connectivity and differentiation of interneurons are thought to be an underlying cause in the emergence of neurodevelopmental disorders such as schizophrenia. Previously, it was suggested that tangential migration of interneurons occurs in a radial glia independent manner. Here, using simultaneous imaging of genetically defined populations of interneurons and radial glia, we demonstrate that dynamic interactions with radial glia can potentially influence the trajectory of interneuronal migration and thus the positioning of interneurons in cerebral cortex. Furthermore, there is extensive local interneuronal migration in tangential direction opposite to that of pallial orientation (i.e., in a medial to lateral direction from cortex to ganglionic eminence) all across the cerebral wall. This counter migration of interneurons may be essential to locally position interneurons once they invade the developing cerebral wall from the ganglionic eminence. Together, these observations suggest that interactions with radial glial scaffold and localized migration within the expanding cerebral wall may play essential roles in the guidance and placement of interneurons in the developing cerebral cortex.}, Author = {Yokota, Yukako and Gashghaei, H. Troy and Han, Christine and Watson, Hannah and Campbell, Kenneth J. and Anton, E. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1932-6203}, Journal = {PLoS ONE}, Keywords = {24 Pubmed search results 2008}, Nlm_Id = {101285081}, Number = {8}, Organization = {UNC Neuroscience Center and the Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.}, Pages = {e794}, Pubmed = {17726524}, Title = {Radial glial dependent and independent dynamics of interneuronal migration in the developing cerebral cortex}, Uuid = {78FCB2FC-8E8C-4DE5-8435-4E55EDC64920}, Volume = {2}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1371/journal.pone.0000794}} @article{Yokoyama:2004, Abstract = {Microglia are considered the only cell population of mesodermal origin in the brain, although their role is not fully understood. The present study demonstrated that rat primary microglial cells expressed nestin, A2B5, and O4 antigens, which are markers for oligodendrocyte precursor cells. Based on these findings, we investigated whether microglial cells generated neurons or macroglial cells. Purified microglial cells were cultured in the presence of 10\%fetal bovine serum for 3 days, followed by culture in the presence of 70\%serum for 2 days. During the two-step culture, microglial cells became highly proliferative and strongly expressed inhibitor of DNA binding (Id) genes, indicative of dedifferentiation of the cells. The dedifferentiated cells also expressed transcription factors that promote differentiation into neurons or macroglial cells. When the dedifferentiated cells were transferred into serum-free medium on poly-L-lysine-coated substrate, a substantial number of the cells rapidly turned into long process-bearing cells, which expressed microtubule-associated protein 2, synapsin I, neurofilament proteins, glial fibrillary acidic protein, or galactocerebroside. When microglial cells were fluorescently labeled through acetylated low-density lipoprotein (LDL) receptors or by a phagocytosis-dependent mechanism, fluorescence-bearing neurons, astrocytes, or oligodendrocytes were observed. Neurospheres, aggregates of neural stem cells, expressed Musashi 1 and epidermal growth factor receptor, but the microglia-derived cells did not. These results suggest a novel role of microglia as multipotential stem cells to give rise to neurons, astrocytes, or oligodendrocytes.}, Author = {Yokoyama, Akiko and Yang, Lihua and Itoh, Suzuka and Mori, Kohji and Tanaka, Junya}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Animals;Cell Differentiation;Alpha;Rats;Astrocytes;Not relevant;Rats, Wistar;11 Glia;Microglia;Support, Non-U.S. Gov't;Oligodendroglia;Intermediate Filament Proteins;Neurons;Cells, Cultured}, Month = {1}, Nlm_Id = {8806785}, Notes = {microglia culture experiments immunocytochemistry}, Number = {1}, Organization = {Department of Physiology, School of Medicine, Ehime University, Ehime, Japan.}, Pages = {96-104}, Pubmed = {14648550}, Title = {Microglia, a potential source of neurons, astrocytes, and oligodendrocytes}, Uuid = {5D91C73B-22D2-4ABA-AAA6-6183206CE6DF}, Volume = {45}, Year = {2004}, url = {papers/Yokoyama_Glia2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/glia.10306}} @article{Yoon:1996, Abstract = {Precursor cells found in the subventricular zone (SVZ) of the adult brain can undergo cell division and migrate long distances before differentiating into mature neurons. We have investigated the possibility of introducing genes stably into this population of cells. Replication-defective adenoviruses were injected into the SVZ of the lateral ventricle of adult mice. The adenoviruses carried a cDNA for the LacZ reporter or the human p75 neurotrophin receptor, for which species-specific antibodies are available. Injection of the viruses into the SVZ led to efficient labeling of neuronal precursors. Two months after viral injection, infected cells were detected in the olfactory bulb, a significant distance from the site of injection. Labeled periglomerular and granular neurons with extensive dendritic arborization were found in the olfactory bulb. These results demonstrate that foreign genes can be efficiently introduced into neuronal precursor cells. Furthermore, adenovirus-directed infection can lead to long-term stable gene expression in progenitor cells found in the adult central nervous system.}, Author = {Yoon, S. O. and Lois, C. and Alvirez, M. and Alvarez-Buylla, A. and Falck-Pedersen, E. and Chao, M. V.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {beta-Galactosidase/biosynthesis;Human;Olfactory Bulb/cytology/physiology;Stereotaxic Techniques;Brain/*physiology;Cytomegalovirus;Neurons/cytology/*physiology;Animal;02 Adult neurogenesis migration;Receptors, Nerve Growth Factor/analysis/*biosynthesis;Genetic Vectors;BB abstr;03 Adult neurogenesis progenitor source;Support, Non-U.S. Gov't;*Gene Transfer Techniques;Cerebral Ventricles/cytology/*physiology;Adenoviridae;Support, U.S. Gov't, P.H.S.;Receptor, Nerve Growth Factor;Mice;Genes, Reporter}, Number = {21}, Organization = {Department of Cell Biology, Cornell University Medical College, New York, NY 10021, USA.}, Pages = {11974-9.}, Title = {Adenovirus-mediated gene delivery into neuronal precursors of the adult mouse brain}, Uuid = {48E9994B-CB7D-4813-B9F3-E8DE1FF07C0F}, Volume = {93}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8876247}} @article{Yoshihara:1999, Abstract = {The wiring patterns among various types of neurons via specific synaptic connections are the basis of functional logic employed by the brain for information processing. This study introduces a powerful method of analyzing the neuronal connectivity patterns by delivering a tracer selectively to specific types of neurons while simultaneously transsynaptically labeling their target neurons. We developed a novel genetic approach introducing cDNA for a plant lectin, wheat germ agglutinin (WGA), as a transgene under the control of specific promoter elements. Using this method, we demonstrate three examples of visualization of specific transsynaptic neural pathways: the mouse cerebellar efferent pathways, the mouse olfactory pathways, and the Drosophila visual pathways. This strategy should greatly facilitate studies on the anatomical and functional organization of the developing and mature nervous system.}, Author = {Yoshihara, Y. and Mizuno, T. and Nakahira, M. and Kawasaki, M. and Watanabe, Y. and Kagamiyama, H. and Jishage, K. and Ueda, O. and Suzuki, H. and Tabuchi, K. and Sawamoto, K. and Okano, H. and Noda, T. and Mori, K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {Efferent Pathways/physiology;*Diagnostic Imaging;Cells, Cultured;Synapses/*physiology;Wheat Germ Agglutinins/*genetics/metabolism;Animal;*Nervous System Physiology;23 Technique;*Transgenes/genetics;Visual Pathways/physiology;Neural Pathways/physiology;Mice, Transgenic/genetics;Drosophila/genetics;Support, Non-U.S. Gov't;Cerebellum/physiology;Olfactory Pathways/physiology;Mice;Neurons/metabolism;*Genetic Techniques;T}, Number = {1}, Organization = {Laboratory for Neurobiology of Synapse, RIKEN Brain Science Institute, Saitama, Japan. yoshihara\@brain.riken.go.jp}, Pages = {33-41.}, Title = {A genetic approach to visualization of multisynaptic neural pathways using plant lectin transgene}, Uuid = {A8647876-282D-4D63-BDAF-51C4F22F57F1}, Volume = {22}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10027287}} @article{Yoshizawa:2002, Abstract = {STEF (Sif- and Tiam1-like exchange factor), a guanine nucleotide exchange factor, was identified as a candidate molecule in regulation of neural development. The STEF gene product specifically activates Rac1, a member of the Rho-like small G proteins. Here we report the detailed examination of the expression profile of the stef gene in the mouse brain. In situ hybridization revealed that the stef gene was expressed in a stage- and region-specific manner in the mouse brain; it was expressed during certain developmental stages in the cerebral cortex, the olfactory bulb, the rostral migratory pathway (RMP) and the hippocampus. In the cerebral cortex, stef transcripts were detected in migrating cells in the intermediate zone as well as neurons in the cortical plate. While the expression in the cerebral cortex was reduced at adult stages, considerable expression was found to be maintained in other regions (RMP, olfactory bulb, hippocampal formation), which are the tissues where neurons continue to undergo morphological remodeling including cellular migration, neurite extension and synapse formation even in adults. Thus, stef gene expression appears to correspond to neuronal morphological changes.}, Author = {Yoshizawa, M. and Hoshino, M. and Sone, M. and Nabeshima, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Mech Dev}, Keywords = {04 Adult neurogenesis factors;C abstr}, Number = {1}, Organization = {Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Yoshidakonoe-cho, Sakyo-ku, 606-8501, Kyoto, Japan}, Pages = {65-8.}, Title = {Expression of stef, an activator of Rac1, correlates with the stages of neuronal morphological development in the mouse brain}, Uuid = {D440CEAA-82B0-4C61-B2D3-02CF7389C364}, Volume = {113}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11900975}} @article{Young:1996, Abstract = {The juvenile subventricular zone (SVZ) normally produces oligodendrocytes. To determine whether juvenile SVZ cells are lineage- restricted or whether they remain multipotential, we labeled SVZ cells and characterized their progeny after 1 week in vitro using cell morphology and antigen expression. Heterogeneous clones comprised of retrovirally labeled neurons and astrocytes or astrocytes and oligodendrocytes were observed, as well as homogeneous clones of neurons, astrocytes or oligodendrocytes. Large type-1 astrocyte clones were most common, and mixed oligodendrocyte/type-1-astrocyte clusters represented 15\%of the total clusters. Twenty five percent of the total clusters contained at least 1 immature neuron. Of 128 clones, 6-10\%contained neurons, astrocytes and oligodendrocytes. From these results we conclude that the juvenile SVZ is a mixture of lineage-restricted, bipotential and multipotential neural progenitors. Using Smart Source Parsing}, Author = {Young, G. M. and Levison, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Dev Neurosci}, Keywords = {beta-Galactosidase/biosynthesis;Oligodendroglia/*cytology/physiology;Cell Differentiation;Stem Cells/cytology/*physiology;Cells, Cultured;Rats;Recombinant Proteins/biosynthesis;Animal;02 Adult neurogenesis migration;Rats, Sprague-Dawley;Aging/*physiology;Retroviridae;Genetic Vectors;BB abstr;03 Adult neurogenesis progenitor source;Brain/*cytology/growth &development;Support, U.S. Gov't, P.H.S.;Neurons/cytology/physiology;Nerve Tissue Proteins/analysis/biosynthesis;Biological Markers/analysis}, Number = {4}, Organization = {Department of Neuroscience and Anatomy, Pennsylvania State University College of Medicine, Hershey, USA.}, Pages = {255-65}, Title = {Persistence of multipotential progenitors in the juvenile rat subventricular zone}, Uuid = {920D8324-D2CC-4D5A-A6EC-1F4B75AFF6DE}, Volume = {18}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8911765}} @article{Young:2007, Abstract = {We determined the embryonic origins of adult forebrain subventricular zone (SVZ) stem cells by Cre-lox fate mapping in transgenic mice. We found that all parts of the telencephalic neuroepithelium, including the medial ganglionic eminence and lateral ganglionic eminence (LGE) and the cerebral cortex, contribute multipotent, self-renewing stem cells to the adult SVZ. Descendants of the embryonic LGE and cortex settle in ventral and dorsal aspects of the dorsolateral SVZ, respectively. Both populations contribute new (5-bromo-2'-deoxyuridine-labeled) tyrosine hydroxylase- and calretinin-positive interneurons to the adult olfactory bulb. However, calbindin-positive interneurons in the olfactory glomeruli were generated exclusively by LGE-derived stem cells. Thus, different SVZ stem cells have different embryonic origins, colonize different parts of the SVZ, and generate different neuronal progeny, suggesting that some aspects of embryonic patterning are preserved in the adult SVZ. This could have important implications for the design of endogenous stem cell-based therapies in the future.}, Author = {Young, Kaylene M. and Fogarty, Matthew and Kessaris, Nicoletta and Richardson, William D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Embryonic Development;Cell Differentiation;research support, non-u.s. gov't;Neuroepithelial Cells;Stem Cells;Mice, Transgenic;comparative study;Olfactory Bulb;Animals;Cell Movement;Cerebral Ventricles;Mice;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {31}, Organization = {Wolfson Institute for Biomedical Research and Department of Biology, University College London, London WC1E 6BT, United Kingdom.}, Pages = {8286-96}, Pii = {27/31/8286}, Pubmed = {17670975}, Title = {Subventricular zone stem cells are heterogeneous with respect to their embryonic origins and neurogenic fates in the adult olfactory bulb}, Uuid = {0D071FE7-CB3C-489A-A706-1349552EA303}, Volume = {27}, Year = {2007}, url = {papers/Young_JNeurosci2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0476-07.2007}} @article{Young:1997, Abstract = {Many investigators studying oligodendrocytes in vitro have sought out cell lines because it has been difficult to obtain sufficient numbers of primary oligodendrocytes for study. This paper describes three methodological improvements that facilitate culturing oligodendrocytes. We show that by detaching progenitor cells using papain instead of trypsin the total yield of oligodendrocyte progenitors can be doubled. We also show that papain can be used to subculture differentiated oligodendrocytes. Finally we report that primary O-2A progenitors can be cryo-preserved, reducing the demand upon laboratory personnel to produce and propagate them. 98149537 0165-0270 Journal Article}, Author = {Young, G. M. and Levison, S. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {J Neurosci Methods}, Keywords = {Cell Separation/methods;Cell Differentiation;Cell Culture/*methods;G abstr;Culture Media, Conditioned;Comparative Study;Rats;Oligodendroglia/*cytology/metabolism;Cell Count;11 Glia;Animal;Cells, Cultured;Papain;Trypsin;Stem Cells/*cytology/metabolism;Cryopreservation/methods}, Number = {2}, Organization = {Department of Neuroscience and Anatomy, College of Medicine, Pennsylvania State University, Hershey 17033, USA.}, Pages = {163-8}, Pubmed = {9489893}, Title = {An improved method for propagating oligodendrocyte progenitors in vitro}, Uuid = {F92848DA-DF01-4A30-9EC6-39E99BB734BC}, Volume = {77}, Year = {1997}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9489893}} @article{Young:1999, Abstract = {The mammalian brain has a high degree of plasticity, with dentate granule cell neurogenesis and glial proliferation stimulated by an enriched environment combining both complex inanimate and social stimulation. Moreover, rodents exposed to an enriched environment both before and after a cerebral insult show improved cognitive performance. One of the most robust associations of environmental enrichment is improved learning and memory in the Morris water maze, a spatial task that mainly involves the hippocampus. Furthermore, clinical evidence showing an association between higher educational attainment and reduced risk of Alzheimer and Parkinson-related dementia indicates that a stimulating environment has positive effects on cerebral health that may provide some resilience to cerebral insults. Here we show that in addition to its effects on neurogenesis, an enriched environment reduces spontaneous apoptotic cell death in the rat hippocampus by 45\%. Moreover, these environmental conditions protect against kainate- induced seizures and excitotoxic injury. The enriched environment induces expression of glial-derived neurotrophic factor and brain- derived neurotrophic factor and increases phosphorylation of the transcription factor cyclic-AMP response element binding protein, indicating that the influence of the environment on spontaneous apoptosis and cerebral resistance to insults may be mediated through transcription factor activation and induction of growth factor expression.}, Author = {Young, D. and Lawlor, P. A. and Leone, P. and Dragunow, M. and During, M. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Nat Med}, Keywords = {Brain-Derived Neurotrophic Factor/biosynthesis/genetics;Rats;Phosphorylation;07 Excitotoxicity Apoptosis;RNA, Messenger/isolation &purification;Animal;Rats, Wistar;*Environment;DNA-Binding Protein, Cyclic AMP-Responsive/metabolism;Male;Kainic Acid/*adverse effects;In Situ Hybridization;*Apoptosis;Support, Non-U.S. Gov't;Seizures/chemically induced/*prevention &control;Nerve Tissue Proteins/biosynthesis/genetics;Dentate Gyrus/growth &development/pathology;Hippocampus/growth &development/*pathology;E-7}, Number = {4}, Organization = {Department of Molecular Medicine, University of Auckland School of Medicine, New Zealand.}, Pages = {448-53.}, Title = {Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective}, Uuid = {62EE34B6-24F1-4420-887A-4F87E8B825DD}, Volume = {5}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10202938}} @article{Young:2008, Abstract = {To facilitate a functional analysis of neuronal connectivity in a mammalian nervous system that is tightly packed with billions of cells, we developed a new technique that uses inducible genetic manipulations in fluorescently labeled single neurons in mice. Our technique, single-neuron labeling with inducible Cre-mediated knockout (SLICK), is achieved by coexpressing a drug-inducible form of Cre recombinase and a fluorescent protein in a small subsets of neurons, thus combining the powerful Cre recombinase system for conditional genetic manipulation with fluorescent labeling of single neurons for imaging. Here, we demonstrate efficient inducible genetic manipulation in several types of neurons using SLICK. Furthermore, we applied SLICK to eliminate synaptic transmission in a small subset of neuromuscular junctions. Our results provide evidence for the long-term stability of inactive neuromuscular synapses in adult animals and demonstrate a Cre-loxP compatible system for dissecting gene functions in single identifiable neurons.}, Author = {Young, Paul and Qiu, Li and Wang, Dongqing and Zhao, Shengli and Gross, James and Feng, Guoping}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:42:21 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Estrogen Antagonists;Animals;Ganglia, Spinal;Integrases;Mice, Transgenic;Mice, Inbred C57BL;Green Fluorescent Proteins;research support, non-u.s. gov't;Mice, Knockout;Potassium Channels;Neurons;Tamoxifen;research support, n.i.h., extramural;Mice;Genes, Reporter;Central Nervous System;Gene Expression;24 Pubmed search results 2008;Luminescent Proteins;Nerve Tissue Proteins}, Month = {6}, Nlm_Id = {9809671}, Number = {6}, Organization = {Department of Neurobiology, Duke University Medical Center, Research Drive, Durham, North Carolina 27710, USA. p.young\@ucc.ie}, Pages = {721-8}, Pii = {nn.2118}, Pubmed = {18454144}, Title = {Single-neuron labeling with inducible Cre-mediated knockout in transgenic mice}, Uuid = {6A2E5C55-9787-4E46-983F-753C397B53B6}, Volume = {11}, Year = {2008}, url = {papers/Young_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2118}} @article{Youngentob:2001, Abstract = {The present study assessed the functional consequences of viral infection with a neurotropic coronavirus, designated MHV OBLV, that specifically targets central olfactory structures. Using standard operant techniques and a 'go, no-go'successive discrimination paradigm, six BALB/c mice were trained to discriminate between the presentation of an air or odor stimulus (three mice for each of the odorants propanol and propyl acetate). Two additional BALB/c mice were trained to discriminate between the presentation of air and the presentation of either vanillin or propionic acid. Following criterion performance, each mouse received an additional 2000 trials of overtraining. At completion of overtraining one mouse from the propanol and propyl acetate groups were allocated as untreated. The remaining six mice were inoculated with 300 microl of the OBLV stock per nostril for a total of 1.5 x 10(6) p.f.u. in 600 microl. Following a 1 month rest, untreated and inoculated animals were again tested on their respective air versus odor discrimination task. Untreated animals immediately performed at criterion levels. In contrast, inoculated animals varied in their capacity to discriminate between air and odorant. Five of the six inoculated mice showed massive disruption of the olfactory bulb, including death of mitral cells; the other was more modestly affected. In addition, the density of innervation of the olfactory mucosa by substance P-containing trigeminal fibers is also affected by inoculation. Those mice that remained anosmic to the training odorants had the most severe reduction in mitral cell number and substance P fiber density among the inoculated animals. 0379-864x Journal Article}, Author = {Youngentob, S. L. and Schwob, J. E. and Saha, S. and Manglapus, G. and Jubelt, B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Chem Senses}, Keywords = {Murine hepatitis virus/*metabolism;Substance P/biosynthesis;Benzaldehydes/analysis;Mice, Inbred BALB C;Air;Propionic Acids/analysis;T pdf;Time Factors;Support, U.S. Gov't, P.H.S.;*Administration, Intranasal;*Smell;Animals;Mice;Olfactory Bulb/metabolism/pathology/*virology;23 Technique;Male}, Number = {8}, Organization = {Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY 13210, USA. youngens\@mail.upstate.edu}, Pages = {953-63}, Title = {Functional consequences following infection of the olfactory system by intranasal infusion of the olfactory bulb line variant (OBLV) of mouse hepatitis strain JHM}, Uuid = {B818E1C1-1A62-4DAC-BB49-6C6111126653}, Volume = {26}, Year = {2001}, url = {papers/Youngentob_ChemSenses2001}} @article{Yozu:2005, Abstract = {The migratory paths of interneurons derived from the ganglionic eminence (GE), and particularly its caudal portion (CGE), remain essentially unknown. To clarify the three-dimensional migration profile of interneurons derived from each part of the GE, we developed a technique involving focal electroporation into a small, defined portion of the telencephalic hemisphere. While the medial GE cells migrated laterally and spread widely throughout the cortex, the majority of the CGE cells migrated caudally toward the caudal-most end of the telencephalon. Time-lapse imaging and an in vivo immunohistochemical study confirmed the existence of a migratory stream depicted by a population of CGE cells directed caudally that eventually reached the hippocampus. Transplantation experiments suggested that the caudal direction of migration of the CGE cells was intrinsically determined as early as embryonic day 13.5. The caudal migratory stream is a novel migratory path for a population of CGE-derived interneurons passing from the subpallium to the hippocampus.}, Author = {Yozu, Masato and Tabata, Hidenori and Nakajima, Kazunori}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {8102140}, Number = {31}, Organization = {Department of Anatomy, Keio University School of Medicine, Tokyo 160-8582, Japan.}, Pages = {7268-77}, Pii = {25/31/7268}, Pubmed = {16079409}, Title = {The caudal migratory stream: a novel migratory stream of interneurons derived from the caudal ganglionic eminence in the developing mouse forebrain}, Uuid = {41C491CE-4F26-400D-9A8D-91D9E309C440}, Volume = {25}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2072-05.2005}} @article{Yu:1976, Abstract = {The effect of a thymidine analog, 5-bromodeoxyuridine (BrdU), on the postnatal development of the cerebellum was studied. Rats were injected with 15 mg per 100 gram body weight of BrdU twice a day for 3 consecutive days from the second day after birth, and were killed at 5, 7, 15, 22 and 35 days of age. One hour prior to killing, the rats were given tritiated thymidine. The cerebellar DNA, RNA, protein and cerebroside, and the incorporation of thymidine were measured. BrdU administration caused a markedly retarded growth of the body and the cerebellum. At 35 days of age, the weights of the body and the cerebellum were 42 and 69\%of the controls. Quantitative measurements of cerebellar nucleic acids and isotope uptake correlated well with previous morphological observation, and indicated that the analog caused a transient inhibition of cell formation and possibly destruction of stem cell population of the external granular layer. This inhibitory effect was compensated later by a more rapid DNA deposition and a prolongation of the period of cell proliferation. However, the restitution was incomplete and resulted in a permanent deficit in the final cell number, as reflected by the reduction in the size of the cerebellum of the BrdU-treated rats. 0006-8993 Journal Article}, Author = {Yu, W. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Brain Res}, Keywords = {A, T abstr;01 Adult neurogenesis general;Neurons/drug effects;DNA/biosynthesis;Rats;Female;Organ Weight/drug effects;Bromodeoxyuridine/*pharmacology;Animals, Newborn;Support, U.S. Gov't, P.H.S.;Animals;Body Weight/drug effects;Age Factors;Cerebellum/cytology/drug effects/*growth &development;Male}, Number = {2}, Pages = {281-91}, Pubmed = {1000291}, Title = {The effect of 5-bromodeoxyuridine on the postnatal development of the rat cerebellum: a biochemical study}, Uuid = {09EE7737-1845-4B49-929A-FD93608980CA}, Volume = {118}, Year = {1976}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1000291}} @article{Yu:2006, Abstract = {The mammalian central nervous system is organized by a variety of cells, such as neurons and glial cells, that are generated from a common progenitor, the neural stem cell (NSC). NSCs are defined as undifferentiated neural cells that are characterized by their high proliferative potential while retaining the capacity for self-renewal and multipotency. NSCs and their progeny may be distinguished by the expression of glycoconjugates (e.g., glycoproteins, glycolipids, and proteoglycans). The carbohydrate antigens carried by glycoconjugates are mainly localized on the plasma membrane surface of the cells and they serve as excellent biomarkers for various stages of cellular differentiation. Thus, they have been utilized as ligands for sorting NSCs or their progeny by cell cytometry. Methods have been established for utilizing polysialic acid-neural cell adhesion molecule (PSA-NCAM), stage-specific embryonic antigen-1 (SSEA-1), and gangliosides for cell sorting. Furthermore, glycoconjugates have also been suggested to have a wide range of receptor and signaling functions in NSCs. For example, basic fibroblast growth factor, an important mitogen of NSCs, requires heparan sulfate proteoglycans and glycosylated cystatin C for activity. Notch signaling, which regulates a wide variety of developmental processes in various cells including NSCs, is modulated by the O-fucose glycan modification. In peripheral nervous system (PNS), the human natural killer-1 (HNK-1) antigen regulates the migration of neural crest cells, cell populations containing the stem cells. Thus, glycoconjugates serve not only as marker molecules, but also as functional molecules as well. In the present review, we discuss the expression pattern and possible functions of glycoconjugates in NSCs.}, Author = {Yu, Robert K. and Yanagisawa, Makoto}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {1871-5273}, Journal = {CNS Neurol Disord Drug Targets}, Keywords = {24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {101269155}, Number = {4}, Organization = {Program in Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, 30912, USA. ryu\@mcg.edu}, Pages = {415-23}, Pubmed = {16918393}, Title = {Glycobiology of neural stem cells}, Uuid = {13AED705-47C7-4650-885E-CBD32F5C0F4E}, Volume = {5}, Year = {2006}} @article{Yu:2002, Abstract = {Duplexes of 21-nt RNAs, known as short-interfering RNAs (siRNAs), efficiently inhibit gene expression by RNA interference (RNAi) when introduced into mammalian cells. We show that siRNAs can be synthesized by in vitro transcription with T7 RNA polymerase, providing an economical alternative to chemical synthesis of siRNAs. By using this method, we show that short hairpin siRNAs can function like siRNA duplexes to inhibit gene expression in a sequence-specific manner. Further, we find that hairpin siRNAs or siRNAs expressed from an RNA polymerase III vector based on the mouse U6 RNA promoter can effectively inhibit gene expression in mammalian cells. U6-driven hairpin siRNAs dramatically reduced the expression of a neuron-specific beta-tubulin protein during the neuronal differentiation of mouse P19 cells, demonstrating that this approach should be useful for studies of differentiation and neurogenesis. We also observe that mismatches within hairpin siRNAs can increase the strand selectivity of a hairpin siRNA, which may reduce self-targeting of vectors expressing siRNAs. Use of hairpin siRNA expression vectors for RNAi should provide a rapid and versatile method for assessing gene function in mammalian cells, and may have applications in gene therapy.}, Author = {Yu, Jenn-Yah Y. and DeRuiter, Stacy L. and Turner, David L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Research Support, Non-U.S. Gov't;Animals;RNA Polymerase III;RNA;Base Sequence;Transfection;23 Technique;RNA, Small Interfering;Genetic Vectors;Cell Line;Research Support, U.S. Gov't, P.H.S.;Plasmids;Neurons;Tubulin Modulators;23 RNAi;Promoter Regions (Genetics);RNA, Untranslated;24 Pubmed search results 2008;Genes, Reporter;Mice;Immunohistochemistry;Molecular Sequence Data;Transcription, Genetic}, Medline = {21980630}, Month = {4}, Nlm_Id = {7505876}, Number = {9}, Organization = {Mental Health Research Institute, Program in Neuroscience, and Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109-0669, USA.}, Pages = {6047-52}, Pii = {092143499}, Pubmed = {11972060}, Title = {RNA interference by expression of short-interfering RNAs and hairpin RNAs in mammalian cells}, Uuid = {876A9993-4240-4827-A85B-49EA455F709D}, Volume = {99}, Year = {2002}, url = {papers/Yu_ProcNatlAcadSciUSA2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.092143499}} @article{Yuan:2004, Abstract = {Self-renewal of stem cells is critical for tissue repair and maintenance of organ integrity in most mammalian systems. The relative asymmetry between self-renewal and differentiation in balance with apoptosis determines the size and durability of a stem-cell pool. Regulation of the cell cycle is one of the fundamental mechanisms underlying determination of cell fate. Absence of p21(Cip1/Waf1), a late G1-phase cyclin-dependent kinase inhibitor (CKI), has previously been shown to enable cell-cycle entry of haematopoietic stem cells, but leads to premature exhaustion of the stem cells under conditions of stress. We show here that deletion of an early G1-phase CKI, p18(INK4C), results in strikingly improved long-term engraftment, largely by increasing self-renewing divisions of the primitive cells in murine transplant models. Therefore, different CKIs have highly distinct effects on the kinetics of stem cells, possibly because of their active position in the cell cycle, and p18(INK4C) appears to be a strong inhibitor limiting the potential of stem-cell self-renewal in vivo. 1465-7392 Journal Article}, Author = {Yuan, Y. and Shen, H. and Franklin, D. S. and Scadden, D. T. and Cheng, T.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Nat Cell Biol}, Keywords = {EE pdf;08 Aberrant cell cycle}, Number = {5}, Organization = {University of Pittsburgh Cancer Institute and Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh PA 15213, USA.}, Pages = {436-42}, Title = {In vivo self-renewing divisions of haematopoietic stem cells are increased in the absence of the early G1-phase inhibitor, p18INK4C}, Uuid = {C5089314-5E92-4AC1-B8E3-1127D437BF3E}, Volume = {6}, Year = {2004}, url = {papers/Yuan_NatCellBiol2004.pdf}} @article{Yuan:2003, Abstract = {Neurons may die as a normal physiological process during development or as a pathological process in diseases. The best-understood mechanism of neuronal cell death is apoptosis, which is regulated by an evolutionarily conserved cellular pathway that consists of the caspase family, the Bcl-2 family, and the adaptor protein Apaf-1. Apoptosis, however, may not be the only cellular mechanism that regulates neuronal cell death. Neuronal cell death may exhibit morphological features of autophagy or necrosis, which differ from that of the canonical apoptosis. This review evaluates the evidence supporting the existence of alternative mechanisms of neuronal cell death and proposes the possible existence of an evolutionarily conserved pathway of necrosis. 0896-6273 Journal Article Review Review, Tutorial}, Author = {Yuan, J. and Lipinski, M. and Degterev, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:01 -0400}, Journal = {Neuron}, Keywords = {EE pdf;Neurons/*physiology;Human;08 Aberrant cell cycle;Cell Death/physiology;Caspases/physiology;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Animals;Apoptosis/*physiology}, Number = {2}, Organization = {Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA. jyuan\@hms.harvard.edu}, Pages = {401-13}, Pubmed = {14556717}, Title = {Diversity in the mechanisms of neuronal cell death}, Uuid = {28B79997-E8A6-41A9-B045-A39E5E42330F}, Volume = {40}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=14556717}} @article{Yun:2003, Abstract = {Parcellation of the mammalian cerebral cortex into distinct areas is essential for proper cortical function; however, the developmental program that results in the genesis of distinct areas is not fully understood. We examined the expression of members of the EphA family-the EphA receptor tyrosine kinases and the ephrin-A ligands-within the developing mouse cerebral cortex, with the aim of characterizing this component of the molecular landscape during cortical parcellation. We found that specific embryonic zones, such as the ventricular, subventricular, intermediate, subplate, and marginal zones, as well as the cortical plate, were positive for particular EphA genes early in corticogenesis (E12-E15). Along with this zone-selective expression, several genes (EphA3, EphA4, EphA5) were evenly expressed along the axes of the developing cortex, whereas one family member (EphA7) was expressed in a distinct anteroposterior pattern. Later in corticogenesis (E16-E18), other EphA family members became selectively expressed, but only within the cortical plate: EphA6 was present posteriorly, and ephrin-A5 was expressed within a middle region. At birth, patterning of EphA gene expression was striking. Thus, we found that the expression of a single EphA gene or a combination of family members can define distinct embryonic zones and anteroposterior regions of the neocortex during development. To examine whether cellular context affects the patterning of EphA expression, we examined gene expression in embryonic cortical cells grown in vitro, such that all cellular contacts are lacking, and in Mash-1 mutant mice, in which thalamocortical connections do not form. We found that the expression patterns of most EphA family members remained stable in these scenarios, whereas the pattern of ephrin-A5 was altered. Taken together, this work provides a comprehensive picture of EphA family expression during mouse corticogenesis and demonstrates that most EphA expression profiles are cell intrinsically based, whereas ephrin-A5 is plastically regulated.}, Author = {Yun, Mihae E. and Johnson, Randall R. and Antic, Anica and Donoghue, Maria J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:46:00 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {10 Development;Cell Culture Techniques;Animals;Transcription Factors;DNA-Binding Proteins;Mice, Mutant Strains;Afferent Pathways;Basic Helix-Loop-Helix Transcription Factors;Receptors, Eph Family;Receptor, EphA7;Receptor, EphA3;Time Factors;Reverse Transcriptase Polymerase Chain Reaction;10 circuit formation;In Situ Hybridization;Research Support, U.S. Gov't, P.H.S.;Thalamus;Receptor, EphA4;Cerebral Cortex;Mice;24 Pubmed search results 2008;Receptor, EphA5;Gene Expression;Research Support, Non-U.S. Gov't}, Medline = {22415406}, Month = {2}, Nlm_Id = {0406041}, Number = {3}, Organization = {Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.}, Pages = {203-16}, Pubmed = {12528186}, Title = {EphA family gene expression in the developing mouse neocortex: regional patterns reveal intrinsic programs and extrinsic influence}, Uuid = {28A90BB3-FDDC-46F2-9BA8-4D187DD075C2}, Volume = {456}, Year = {2003}, url = {papers/Yun_JCompNeurol2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/cne.10498}} @article{Yuste:1997, Abstract = {The computations performed within cortex are likely to be determined by its internal dynamics in addition to its pattern of afferent input. As a step toward characterizing these dynamics, we have imaged electrical activity in slices from rat primary visual cortex stained with the voltage-sensitive dye di-4-ANEPPS. In response to electrical stimulation two fluorescence signals of similar maximum amplitude are elicited, (i) A fast signal that peaks in a few milliseconds, is dependent on membrane voltage, and has a significant presynaptic component. This signal can be used to image electrical activity ratiometrically. (ii) A slow signal that peaks a few seconds after stimulation, does not reflect voltage changes, and may originate from changes in scattering properties of the slice and from interactions of the dye with the cells. The spatial pattern of fast signals obtained in response to focal stimulation of coronal slices is consistent with known interlaminar projection patterns. In tangential slices, imaging of fast signals reveals clustered horizontal responses. Finally, imaging of fast signals during epileptiform activation of the disinhibited circuit reveals propagating responses, without evidence for modular activation.}, Author = {Yuste, R. and Tank, D. W. and Kleinfeld, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Fluorescent Dyes;Electric Stimulation;Electrophysiology;In Vitro;Evoked Potentials;Image Processing, Computer-Assisted;Rats;Animals;Spectrometry, Fluorescence;Rats, Sprague-Dawley;21 Calcium imaging;Nerve Net;Cerebral Cortex;21 Neurophysiology;Cell Nucleus;Receptors, Neurotransmitter;24 Pubmed search results 2008;Pyridinium Compounds;Research Support, Non-U.S. Gov't}, Medline = {97422092}, Month = {9}, Nlm_Id = {9110718}, Number = {6}, Organization = {Department of Biological Sciences, Columbia University, New York, NY 10027, USA.}, Pages = {546-58}, Pubmed = {9276179}, Title = {Functional study of the rat cortical microcircuitry with voltage-sensitive dye imaging of neocortical slices}, Uuid = {376A894E-7C91-4570-B6C7-5DEAEBB4C314}, Volume = {7}, Year = {1997}, url = {papers/Yuste_CerebCortex1997.pdf}} @article{Yuste:2005, Abstract = {Fluorescence microscopy has undergone a renaissance in the last decade. The introduction of green fluorescent protein (GFP) and two-photon microscopy has allowed systematic imaging studies of protein localization in living cells and of the structure and function of living tissues. The impact of these and other new imaging methods in biophysics, neuroscience, and developmental and cell biology has been remarkable. Further advances in fluorophore design, molecular biological tools and nonlinear and hyper-resolution microscopies are poised to profoundly transform many fields of biological research.}, Author = {Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1548-7091}, Journal = {Nat Methods}, Keywords = {Research Support, Non-U.S. Gov't;21 Neurophysiology;21 Calcium imaging;Microscopy, Fluorescence;Green Fluorescent Proteins;Animals;Humans;24 Pubmed search results 2008;review}, Month = {12}, Nlm_Id = {101215604}, Number = {12}, Organization = {Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10027, USA. rmy5\@columbia.edu}, Pages = {902-4}, Pii = {nmeth1205-902}, Pubmed = {16299474}, Title = {Fluorescence microscopy today}, Uuid = {04F5E1F4-69EE-4D3F-80BB-44D405F6E0E8}, Volume = {2}, Year = {2005}, url = {papers/Yuste_NatMethods2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nmeth1205-902}} @article{Yuste:2004, Author = {Yuste, Rafael and Bonhoeffer, Tobias}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {Purkinje Cells;Research Support, Non-U.S. Gov't;Dendrites;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;Pseudopodia;21 Calcium imaging;Humans;Animals;24 Pubmed search results 2008;review}, Month = {1}, Nlm_Id = {100962781}, Number = {1}, Organization = {Department of Biological Sciences, Columbia University, New York, New York 10027, USA. rmy5\@columbia.edu}, Pages = {24-34}, Pii = {nrn1300}, Pubmed = {14708001}, Title = {Genesis of dendritic spines: insights from ultrastructural and imaging studies}, Uuid = {F127F77D-6534-4402-B31E-7441F8F280B7}, Volume = {5}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1300}} @article{Yuste:2005a, Abstract = {Vertebrate spinal cord and brainstem central pattern generator (CPG) circuits share profound similarities with neocortical circuits. CPGs can produce meaningful functional output in the absence of sensory inputs. Neocortical circuits could be considered analogous to CPGs as they have rich spontaneous dynamics that, similar to CPGs, are powerfully modulated or engaged by sensory inputs, but can also generate output in their absence. We find compelling evidence for this argument at the anatomical, biophysical, developmental, dynamic and pathological levels of analysis. Although it is possible that cortical circuits are particularly plastic types of CPG ('learning CPGs'), we argue that present knowledge about CPGs is likely to foretell the basic principles of the organization and dynamic function of cortical circuits.}, Author = {Yuste, Rafael and MacLean, Jason N. and Smith, Jeffrey and Lansner, Anders}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1471-003X}, Journal = {Nat Rev Neurosci}, Keywords = {24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;21 Neurophysiology;Research Support, U.S. Gov't, P.H.S.;21 Calcium imaging;Research Support, N.I.H., Extramural;Nerve Net;Animals;Humans;Cerebral Cortex;review;21 Cortical oscillations}, Month = {6}, Nlm_Id = {100962781}, Number = {6}, Organization = {Department of Biological Sciences, Columbia University, 1212 Amsterdam Avenue, Box 2435, New York 10027, USA. rmy5\@columbia.edu}, Pages = {477-83}, Pii = {nrn1686}, Pubmed = {15928717}, Title = {The cortex as a central pattern generator}, Uuid = {6CD8085F-BAB8-475B-91D3-F986D1F64550}, Volume = {6}, Year = {2005}, url = {papers/Yuste_NatRevNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nrn1686}} @article{Yuste:1995, Abstract = {Most excitatory synaptic connections occur on dendritic spines. Calcium imaging experiments have suggested that spines constitute individual calcium compartments, but recent results have challenged this idea. Using two-photon microscopy to image fluorescence with high resolution in strongly scattering tissue, we measured calcium dynamics in spines from CA1 pyramidal neurons in slices of rat hippocampus. Subthreshold synaptic stimulation and spontaneous synaptic events produced calcium accumulations that were localized to isolated spines, showed stochastic failure, and were abolished by postsynaptic blockers. Single somatic spikes induced fast-peaking calcium accumulation in spines throughout the cell. Pairing of spikes with synaptic stimulation was frequently cooperative, that is, it resulted in supralinear calcium accumulations. We conclude: (1) calcium channels exist in spine heads; (2) action potentials invade the spines; (3) spines are individual calcium compartments; and (4) spines can individually detect the temporal coincidence of pre- and postsynaptic activity, and thus serve as basic functional units of neuronal integration.}, Author = {Yuste, R. and Denk, W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Fluorescent Dyes;Animals;Synapses;Cells, Cultured;Rats;Research Support, U.S. Gov't, Non-P.H.S.;Hippocampus;Pyramidal Cells;Calcium;Microscopy, Fluorescence;21 Calcium imaging;Dendrites;Organic Chemicals;Action Potentials;21 Neurophysiology;Differential Threshold;Calcium Channels;24 Pubmed search results 2008}, Medline = {95312105}, Month = {6}, Nlm_Id = {0410462}, Number = {6533}, Organization = {Biological Computation Research Department, AT&T Bell Laboratories, Murray Hill, New Jersey 07974, USA.}, Pages = {682-4}, Pubmed = {7791901}, Title = {Dendritic spines as basic functional units of neuronal integration}, Uuid = {719028A5-F508-4F09-AE7D-EB7211788CA2}, Volume = {375}, Year = {1995}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/375682a0}} @article{Yuste:1991, Abstract = {We assessed the pathways by which excitatory and inhibitory neurotransmitters elicit postsynaptic changes in [Ca2+]i in brain slices of developing rat and cat neocortex, using fura 2. Glutamate, NMDA, and quisqualate transiently elevated [Ca2\%]i in all neurons. While the quisqualate response relied exclusively on voltage-gated Ca2+ channels, almost all of the NMDA-induced Ca2+ influx was via the NMDA ionophore itself, rather than through voltage-gated Ca2+ channels. Glutamate itself altered [Ca2+]i almost exclusively via the NMDA receptor. Furthermore, synaptically induced Ca2+ entry relied almost completely on NMDA receptor activation, even with low-frequency stimulation. The inhibitory neurotransmitter GABA also increased [Ca2+]i, probably via voltage-sensitive Ca2+ channels, whereas the neuromodulator acetylcholine caused Ca2+ release from intracellular stores via a muscarinic receptor. Low concentrations of these agonists produced nonperiodic [Ca2+]i oscillations, which were temporally correlated in neighbouring cells. Optical recording with Ca2(+)-sensitive indicators may thus permit the visualization of functional networks in developing cortical circuits.}, Author = {Yuste, R. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {gamma-Aminobutyric Acid;Animals;Biological Transport, Active;Quisqualic Acid;Rats;Glutamic Acid;21 Epilepsy;Neurotransmitter Agents;Calcium;Acetylcholine;21 Calcium imaging;Glutamates;N-Methylaspartate;Neurons;21 Neurophysiology;Cerebral Cortex;Calcium Channels;Carbachol;24 Pubmed search results 2008;Receptors, N-Methyl-D-Aspartate;Cats;Research Support, Non-U.S. Gov't}, Medline = {91158980}, Month = {3}, Nlm_Id = {8809320}, Number = {3}, Organization = {Laboratory of Neurobiology, Rockefeller University, New York, New York 10021.}, Pages = {333-44}, Pii = {0896-6273(91)90243-S}, Pubmed = {1672071}, Title = {Control of postsynaptic Ca2+ influx in developing neocortex by excitatory and inhibitory neurotransmitters}, Uuid = {732F57C7-0155-11DB-9E68-000D9346EC2A}, Volume = {6}, Year = {1991}, url = {papers/Yuste_Neuron1991.pdf}} @article{Yuste:1995a, Abstract = {The mammalian neocortex consists of columnar circuits, whose development may be controlled by patterns of spontaneous activity. Columnar domains of spontaneously coactive neurons were previously described using Ca2+ imaging of slices from developing rat neocortex. We have now investigated the cellular mechanisms responsible for the coactivation of these domains. The activation starts in the center of a domain and spreads at speeds of approximately 100 microns/s. Domains occur in the presence of tetrodotoxin but are blocked by the gap junction blockers halothane and octanol. Simultaneous intracellular and optical recordings from dye-coupled cells reveal functional coupling between developing neocortical neurons. These data support the hypothesis that a neuronal domain results from the spontaneous excitation of one or a few trigger neurons that subsequently activate, either electrically or biochemically, the rest of the cells via gap junctions.}, Author = {Yuste, R. and Nelson, D. A. and Rubin, W. W. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-04-06 11:18:12 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Fura-2;Electrophysiology;Animals;Rats;Comparative Study;Synaptic Transmission;Kinetics;Calcium;Gap Junctions;Tetrodotoxin;21 Calcium imaging;Octanols;Cold;Research Support, U.S. Gov't, P.H.S.;21 Neurophysiology;Halothane;Neurons;Somatosensory Cortex;21 Cortical oscillations;Research Support, Non-U.S. Gov't;electrical coupling;development;Neocortex;optical physiology;calcium imaging}, Medline = {95127234}, Month = {1}, Nlm_Id = {8809320}, Number = {1}, Organization = {Biological Computation Research Department, AT&T Bell Laboratories, Murray Hill, New Jersey 07974.}, Pages = {7-17}, Pii = {0896-6273(95)90236-8}, Pubmed = {7826643}, Title = {Neuronal domains in developing neocortex: mechanisms of coactivation}, Uuid = {A48819FB-6E8E-49B1-9EC1-CD17BD453D45}, Volume = {14}, Year = {1995}, url = {papers/Yuste_Neuron1995.pdf}} @article{Yuste:1996, Abstract = {0896-6273 Historical Article Journal Article Review Review, Academic}, Author = {Yuste, R. and Tank, D. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Neuron}, Keywords = {18 Classic Neuroanatomy Physiology;History of Medicine, 20th Cent.;Neurons/physiology/*ultrastructure;History of Medicine, 19th Cent.;Motor Neurons/physiology;Human;Action Potentials;Support, U.S. Gov't, Non-P.H.S.;Electrophysiology;Animals;M pdf;Dendrites/*physiology/ultrastructure}, Number = {4}, Organization = {Department of Biological Sciences, Columbia University, New York, New York 10027, USA.}, Pages = {701-16}, Title = {Dendritic integration in mammalian neurons, a century after Cajal}, Uuid = {6DF1066C-CAC1-44D7-B85E-321B3A111DAE}, Volume = {16}, Year = {1996}, url = {papers/Yuste_Neuron1996.pdf}} @article{Yuste:2005b, Abstract = {Neocortical interneurons are very diverse in morphological, physiological, molecular, and developmental characteristics. Recent work is discovering strong correlations between these phenotypic features, confirming the intuition of Cajal and Lorente that distinct classes of interneurons exist, each presumably mediating a different circuit function. A paper by Butt et al. in this issue of Neuron describes correlations between the developmental origin of interneurons and their anatomical, electrophysiological, and molecular properties. An effort to standardize the nomenclature of interneurons is underway. Because different interneuron subtypes have different ontogenic origin, they could be classified based on their developmental specification by transcription factors.}, Author = {Yuste, Rafael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {12 Interneuron development;Research Support, Non-U.S. Gov't;Neocortex;comment;Electrophysiology;Animals;editorial;Interneurons;Cell Lineage;review}, Month = {11}, Nlm_Id = {8809320}, Number = {4}, Organization = {Howard Hughes Medical Institute, Department of Biological Sciences, Columbia University, New York, New York 10027.}, Pages = {524-7}, Pii = {S0896-6273(05)00954-2}, Pubmed = {16301166}, Title = {Origin and classification of neocortical interneurons}, Uuid = {D95F494E-4CAD-4488-AFD3-395F61D6B79B}, Volume = {48}, Year = {2005}, url = {papers/Yuste_Neuron2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2005.11.012}} @article{Yuste:1992, Abstract = {The mammalian neocortex consists of a mosaic of columnar units whose development is poorly understood. Optical recordings of brain slices labeled with the fluorescent calcium indicator fura-2 revealed that the neonatal rat cortex was partitioned into distinct domains of spontaneously coactive neurons. In tangential slices, these domains were 50 to 120 micrometers in diameter; in coronal slices they spanned several cortical layers and resembled columns found in the adult cortex. In developing somatosensory cortex, domains were smaller than, and distinct from, the barrels, which represent sensory input from a single vibrissa. The neurons within each domain were coupled by gap junctions. Thus, nonsynaptic communication during cortical development defines discrete multicellular patterns that could presage adult functional architecture.}, Author = {Yuste, R. and Peinado, A. and Katz, L. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0036-8075}, Journal = {Science}, Keywords = {Fura-2;10 Development;Fluorescent Dyes;Animals;Image Processing, Computer-Assisted;Rats;10 Structural plasticity;Beta;Cell Communication;Intercellular Junctions;Calcium;Tetrodotoxin;Computer Simulation;Support, Non-U.S. Gov't;Action Potentials;10 Spiny stellate;Cerebral Cortex;21 Neurophysiology;Neurons;Support, U.S. Gov't, P.H.S.;21 Cortical oscillations;Brain Mapping}, Medline = {92358212}, Month = {7}, Nlm_Id = {0404511}, Number = {5070}, Organization = {Department of Neurobiology, Duke University Medical Center, Durham, NC 27710.}, Pages = {665-9}, Pubmed = {1496379}, Title = {Neuronal domains in developing neocortex}, Uuid = {C22727F4-5C2D-4776-8F0A-3FF467F1D63D}, Volume = {257}, Year = {1992}, url = {papers/Yuste_Science1992.pdf}} @article{Yuval-Greenberg:2008, Abstract = {The induced gamma-band EEG response (iGBR) recorded on the scalp is widely assumed to reflect synchronous neural oscillation associated with object representation, attention, memory, and consciousness. The most commonly reported EEG iGBR is a broadband transient increase in power at the gamma range approximately 200-300 ms following stimulus onset. A conspicuous feature of this iGBR is the trial-to-trial poststimulus latency variability, which has been insufficiently addressed. Here, we show, using single-trial analysis of concomitant EEG and eye tracking, that this iGBR is tightly time locked to the onset of involuntary miniature eye movements and reflects a saccadic "spike potential." The time course of the iGBR is related to an increase in the rate of saccades following a period of poststimulus saccadic inhibition. Thus, whereas neuronal gamma-band oscillations were shown conclusively with other methods, the broadband transient iGBR recorded by scalp EEG reflects properties of miniature saccade dynamics rather than neuronal oscillations.}, Author = {Yuval-Greenberg, Shlomit and Tomer, Orr and Keren, Alon S. and Nelken, Israel and Deouell, Leon Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1097-4199}, Journal = {Neuron}, Keywords = {Photic Stimulation;Electroencephalography;research support, non-u.s. gov't;Adult;Saccades;Female;Scalp;Fixation, Ocular;Psychomotor Performance;Form Perception;Reaction Time;Humans;Brain;Male;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {8809320}, Number = {3}, Organization = {Department of Psychology, The Hebrew University of Jerusalem, Jerusalem 91905, Israel. shlomit.greenberg\@mail.huji.ac.il}, Pages = {429-41}, Pii = {S0896-6273(08)00301-2}, Pubmed = {18466752}, Title = {Transient induced gamma-band response in EEG as a manifestation of miniature saccades}, Uuid = {DA9CB34E-97C3-4C3B-AD09-780976BF752B}, Volume = {58}, Year = {2008}, url = {papers/Yuval-Greenberg_Neuron2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2008.03.027}} @article{Zachary:1997, Abstract = {Motor neuron degeneration caused by ts1 MoMuLV occurs by an indirect mechanism and hypothetically appears associated with a two-cell or three-cell pathogenesis hypothesis. The first step in this hypothesis is associated with a small subset of resident microglial cells that serve as the principal target cells for ts1 MoMuLV infection. The second step is likely linked to trophic events, probably mediated by cytokines, that lead to hypertrophy and activation of a substantial number of additional microglial cells (autocrine effect) and adjacent astrocytes (paracrine effect). The third step in this hypothesis appears related to indirect neuronal degeneration mediated by cytotoxins produced by activated microglial cells and astrocytes. In this last step, motor neurons located within these foci of activated microglial cells and astrocytes are 'innocent bystander cells' and degenerate and die due to paracrine effects. The mechanism of motor neuron degeneration is poorly understood but is likely linked to a sequential cascade of trophic factors and cytokines resulting in a final common pathway for motor neuron death involving production of oxidative radicals, excitatory aminoacid neurotransmitter-like substances, prostaglandins, or nitric oxide.}, Author = {Zachary, J. F. and Baszler, T. V. and French, R. A. and Kelley, K. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {1359-4184}, Journal = {Mol Psychiatry}, Keywords = {Nerve Degeneration;Animals;Cells, Cultured;review, tutorial;Tumor Virus Infections;review;Microglia;Not relevant;11 Glia;Spinal Cord;Retroviridae Infections;Animals, Newborn;Moloney murine leukemia virus;Neurons;Motor Neuron Disease;Mice;Cytotoxins;Brain Stem}, Medline = {97260132}, Month = {3}, Nlm_Id = {9607835}, Number = {2}, Organization = {College of Veterinary Medicine, University of Illinois, Urbana, USA. zacharyj\@ux1.cso.uiuc.edu}, Pages = {104-6}, Pubmed = {9106227}, Title = {Mouse Moloney leukemia virus infects microglia but not neurons even though it induces motor neuron disease}, Uuid = {131409D4-B893-43F7-AE16-771C6495460B}, Volume = {2}, Year = {1997}} @article{Zador:2007, Author = {Zador, Anthony and Mombaerts, Peter}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {21 Neurophysiology;editorial;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {9111376}, Number = {4}, Organization = {Cold Spring Harbor Laboratory, 1 Bungtown Rd, CSH, NY 11724, United States.}, Pages = {395-6}, Pii = {S0959-4388(07)00103-1}, Pubmed = {17904352}, Title = {Neuronal circuitry and population activity}, Uuid = {28B67E9F-03AF-4ECE-AF41-AC9A060C8C33}, Volume = {17}, Year = {2007}, url = {papers/Zador_CurrOpinNeurobiol2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2007.09.001}} @article{Zarbalis:2007, Abstract = {We report the identification of a hypomorphic mouse allele for Foxc1 (Foxc1(hith)) that survives into adulthood revealing previously unknown roles for Foxc1 in development of the skull and cerebral cortex. This line of mice was recovered in a forward genetic screen using ENU mutagenesis to identify mutants with cortical defects. In the hith allele a missense mutation substitutes a Leu for a conserved Phe at amino acid 107, leading to destabilization of the protein without substantially altering transcriptional activity. Embryonic and postnatal histological analyses indicate that diminished Foxc1 protein expression in all three layers of meningeal cells in Foxc1(hith/hith) mice contributes to the cortical and skull defects in mutant mice and that the prominent phenotypes appear as the meninges differentiate into pia, arachnoid, and dura. Careful analysis of the cortical phenotypes shows that Foxc1(hith/hith) mice display detachment of radial glial endfeet, marginal zone heterotopias, and cortical dyslamination. These abnormalities have some features resembling defects in type 2 (cobblestone) lissencephaly or congenital muscular dystrophies but appear later in corticogenesis because of the delay in breakdown of the basement membrane. Our data reveal that the meninges regulate the development of the skull and cerebral cortex by controlling aspects of the formation of these neighboring structures. Furthermore, we provide evidence that defects in meningeal differentiation can lead to severe cortical dysplasia.}, Author = {Zarbalis, Konstantinos and Siegenthaler, Julie A. and Choe, Youngshik and May, Scott R. and Peterson, Andrew S. and Pleasure, Samuel J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Aging;Cell Differentiation;research support, non-u.s. gov't;Ethylnitrosourea;Forkhead Transcription Factors;Point Mutation;Meninges;research support, n.i.h., extramural;Animals;Mice;Cerebral Cortex;Neurons;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {35}, Organization = {Department of Neurology, University of California, 1550 Fourth Street, San Francisco, CA 94158, USA.}, Pages = {14002-7}, Pii = {0702618104}, Pubmed = {17715063}, Title = {Cortical dysplasia and skull defects in mice with a Foxc1 allele reveal the role of meningeal differentiation in regulating cortical development}, Uuid = {401FE36B-006F-441F-A88C-6DCE644D91EA}, Volume = {104}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0702618104}} @article{Zeev-Brann:1998, Abstract = {The poor ability of injured central nervous system (CNS) axons to regenerate has been correlated, at least partially, with a limited and suppressed postinjury inflammatory response. A key cell type in the inflammatory process is the macrophage, which can respond in various ways, depending on the conditions of stimulation. The aim of this study is to compare the activities of macrophages or microglia when encountering CNS and peripheral nervous systems (PNS), on the assumption that nerve-related differences in the inflammatory response may have implications for tissue repair and thus for nerve regeneration. Phagocytic activity of macrophages or of isolated brain-derived microglia was enhanced upon their exposure to sciatic (PNS) nerve segments, but inhibited by exposure to optic (CNS) nerve segments. Similarly, nitric oxide production by macrophages or microglia was induced by sciatic nerve segments but not by optic nerve segments. The previously demonstrated presence of a resident inhibitory activity in CNS nerve, could account, at least in part, for the inhibited phagocytic activity of blood-borne macrophages in CNS nerve as well as of microglia resident in the brain. It seems that the CNS microglia are reversibly immunosuppressed by the CNS environment, at least with respect to the activities examined here. It also appears from this study that the weak induction of early healing-related activities of macrophages/microglia in the environment of CNS might explain the subsequent failure of this environment to acquire growth-supportive properties in temporal and spatial synchrony with the needs of regrowing axons.}, Author = {Zeev-Brann, A. B. and Lazarov-Spiegler, O. and Brenner, T. and Schwartz, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Phagocytosis;Animals;Cells, Cultured;Macrophages;Rats;Transforming Growth Factor beta;Comparative Study;Microglia;Optic Nerve;Sciatic Nerve;Macrophage Activation;Culture Media, Conditioned;Not relevant;Rats, Wistar;11 Glia;Nerve Regeneration;Male;Coculture;Organ Specificity;Central Nervous System;Optic Nerve Injuries;Nitric Oxide;Organ Culture;Inflammation;Peripheral Nerves}, Medline = {98295560}, Month = {7}, Nlm_Id = {8806785}, Number = {3}, Organization = {Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.}, Pages = {181-90}, Pii = {10.1002/(SICI)1098-1136(199807)23:3<181::AID-GLIA1>3.0.CO;2-8}, Pubmed = {9633803}, Title = {Differential effects of central and peripheral nerves on macrophages and microglia}, Uuid = {5CDDE5D7-1CD5-43E3-879A-991ACF13AF76}, Volume = {23}, Year = {1998}} @article{Zeringue:2004, Abstract = {The techniques evolving from the rapidly developing field of small RNAs promise accessible approaches to dissecting cellular and molecular mechanisms of higher brain function. Here, a current overview of the technology is presented, along with an outline of how these approaches might help neuroscientists to more rapidly uncover the cellular and molecular bases of behavior.}, Author = {Zeringue, Henry C. and Constantine-Paton, Martha}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0959-4388}, Journal = {Curr Opin Neurobiol}, Keywords = {Neurons;RNA, Messenger;RNA, Small Interfering;Models, Animal;24 Pubmed search results 2008;21 Neurophysiology;Nerve Tissue Proteins;RNA Interference;Gene Targeting;Animals;Brain;Humans;review;Genetic Vectors}, Month = {10}, Nlm_Id = {9111376}, Number = {5}, Organization = {Department of Biology, McGovern Institute for Brain Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.}, Pages = {654-9}, Pii = {S0959-4388(04)00123-0}, Pubmed = {15464901}, Title = {Post-transcriptional gene silencing in neurons}, Uuid = {82E249AD-F6E6-4B7C-8210-A763A7FD8534}, Volume = {14}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.conb.2004.08.009}} @article{Zerlin:2004, Abstract = {The subventricular zone (SVZ) of the developing mammalian forebrain gives rise to astrocytes and oligodendrocytes in the neocortex and white matter, and neurons in the olfactory bulb in perinatal life. We have examined the developmental fates and spatial distributions of the descendants of single SVZ cells by infecting them in vivo at postnatal day 0-1 (P0-1) with a retroviral "library". In most cases, individual SVZ cells gave rise to either oligodendrocytes or astrocytes, but some generated both types of glia. Members of glial clones can disperse widely through the gray and white matter. Progenitors continued to divide after stopping migration, generating clusters of related cells. However, the progeny of a single SVZ cell does not differentiate synchronously: individual clones contained both mature and less mature glia after short or long intervals. For example, progenitors that settled in the white matter generated three types of clonal oligodendrocyte clusters: those composed of only myelinating oligodendrocytes, of both myelinating oligodendrocytes and non-myelinating oligodendrocytes, or of only non-myelinating cells of the oligodendrocyte lineage. Thus, some progenitors do not fully differentiate, but remain immature and may continue to cycle well into adult life.}, Author = {Zerlin, Marielba and Milosevic, Ana and Goldman, James E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {Staining and Labeling;Cell Differentiation;Neuroglia;Rats, Sprague-Dawley;03 Adult neurogenesis progenitor source;Rats;Retroviridae;Stem Cells;11 Glia;Support, U.S. Gov't, P.H.S.;Animals, Newborn;Prosencephalon;Animals;Cell Movement;Cell Lineage}, Month = {6}, Nlm_Id = {0372762}, Number = {1}, Organization = {Department of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.}, Pages = {200-13}, Pii = {S0012160604001575}, Pubmed = {15136150}, Title = {Glial progenitors of the neonatal subventricular zone differentiate asynchronously, leading to spatial dispersion of glial clones and to the persistence of immature glia in the adult mammalian CNS}, Uuid = {7CB6A8D9-71EE-49C1-BF35-ED4B7653A6D5}, Volume = {270}, Year = {2004}, url = {papers/Zerlin_DevBiol2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.ydbio.2004.02.024}} @article{Zerlin:1995, Abstract = {Recent studies using retroviral labeling of subventricular zone (SVZ) progenitors in vivo in neonatal rats have directly demonstrated the generation of both astrocytes and oligodendrocytes from these progenitors. In the present study, we used a recombinant retroviral vector encoding beta-galactosidase, and analyzed brains within the first week after retroviral injection to trace the early routes that SVZ cells take as they migrate into white matter and cortex and characterized the early morphological and antigenic changes that accompanied their differentiation. SVZ cells follow specifically definable migratory routes as they colonize the cortex and subcortical white matter. Glial progenitors do not populate the cortex in a systematic, laminar fashion, as do neuroblasts. The abundance of labeled progenitors in radial arrangements and the close apposition of many immature cells to vimentin+ radial glial processes, suggest that glial progenitors migrate along radial glia. Labeled SVZ cells, which displayed a simple, unipolar or bipolar morphology, lacked detectable vimentin and nestin intermediate filaments. Similarly, beta-galactosidase-positive cells in white matter lacked these filaments. In contrast, labeled, multipolar cells in the cortex, and a few of the immature-appearing cortical cells expressed nestin and vimentin. At these early time points, GFAP was not detected in beta-galactosidase-labeled cells. Multipolar cells in cortex frequently displayed processes extending toward and contacting blood vessels. These observations suggest that the expression of nestin and vimentin occurs after progenitors emigrate from the SVZ and that filament expression and contact with blood vessels represent an early stage of astrocyte differentiation. eng Journal Article}, Author = {Zerlin, M. and Levison, S. W. and Goldman, J. E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Journal = {J Neurosci}, Keywords = {Neurons/*physiology;02 Adult neurogenesis migration;beta-Galactosidase/metabolism;Prosencephalon/cytology/*metabolism;Cerebral Cortex/cytology;Rats;Cell Aging;Cerebral Ventricles/cytology/*metabolism;Intermediate Filament Proteins/*metabolism;Animal;Microglia/physiology;B abstr;Support, U.S. Gov't, P.H.S.;Animals, Newborn;Cell Movement;Morphogenesis}, Number = {11}, Organization = {Department of Pathology, Columbia University College of P&S, New York, New York 10032, USA.}, Pages = {7238-49.}, Title = {Early patterns of migration, morphogenesis, and intermediate filament expression of subventricular zone cells in the postnatal rat forebrain}, Uuid = {9B054116-E557-444D-86CF-F2D9BDBEE9A2}, Volume = {15}, Year = {1995}} @article{Zesiger:2002, Abstract = {A 20-year-old man with bilateral parasagittal occipitoparietal polymicrogyria and epilepsy, from whom normal functional magnetic resonance imaging and electroencephalogram responses to visual stimuli were obtained, was found to have no visual perceptual deficits. This suggests that microgyric cortex can perform normal visual functions, despite its gross structural abnormalities.}, Author = {Zesiger, Pascal and Kiper, Daniel and Maeder, Philippe and Deonna, Thierry and Innocenti, Giorgio M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0364-5134}, Journal = {Ann Neurol}, Keywords = {Visual Cortex;Laterality;Psychophysics;Visual Perception;Adolescent;Magnetic Resonance Imaging;Human;Not relevant;11 Glia;Vision;Parietal Lobe;Neuropsychological Tests;Male;Support, Non-U.S. Gov't;case reports}, Medline = {22235344}, Month = {10}, Nlm_Id = {7707449}, Number = {4}, Organization = {Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland.}, Pages = {492-8}, Pubmed = {12325079}, Title = {Preserved visual function in a case of occipitoparietal microgyria}, Uuid = {CF88A61D-1A50-4348-ABA6-DCF3DE03BC6E}, Volume = {52}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/ana.10327}} @article{Zha:2005, Abstract = {We examined the regulation of dendritic spines and synapses by epileptiform activity (EA) in rat hippocampal slice cultures. EA, which was induced by a GABA(A) receptor inhibitor, gabazine, reduced pyramidal neuron spine density by approximately 50\%after 48 h and also caused an increase in the average length of remaining spines. To directly determine the effects of EA on synapses, we used fluorescent protein-tagged PSD95, which marks postsynaptic densities. EA induced a net loss of synapses on spines but not shafts; conversely, activity blockade (TTX) induced a loss of shaft synapses. Time-lapse confocal imaging in live tissue slices revealed that EA (1) shifts the balance of synapse gain and loss in dendrites leading to a net loss of spine synapses and (2) induces the formation of new filopodia-like dendritic structures having abnormally slow motility. These results identify EA-induced changes in the density and distribution of synaptic structures on dendrites.}, Author = {Zha, Xiang-Ming M. and Green, Steven H. and Dailey, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1044-7431}, Journal = {Mol Cell Neurosci}, Keywords = {research support, n.i.h., extramural ;Synaptic Membranes;Animals;Synapses;Rats;Neuronal Plasticity;research support, u.s. gov't, p.h.s. ;Synaptic Transmission;Pyridazines;Epilepsy;Dendritic Spines;Hippocampus;11 Glia;Organ Culture Techniques;Animals, Newborn;21 Neurophysiology;Intracellular Signaling Peptides and Proteins;Down-Regulation;21 Activity-development;GABA Antagonists;Sodium Channel Blockers;24 Pubmed search results 2008;Pseudopodia;Membrane Proteins}, Month = {8}, Nlm_Id = {9100095}, Number = {4}, Organization = {Department of Biological Sciences, University of Iowa, Iowa City, IA 52242-1324, USA.}, Pages = {494-506}, Pii = {S1044-7431(05)00094-1}, Pubmed = {15953736}, Title = {Regulation of hippocampal synapse remodeling by epileptiform activity}, Uuid = {2E29EB25-2CE7-4F7E-A30D-6FF3B06672AD}, Volume = {29}, Year = {2005}, url = {papers/Zha_MolCellNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.mcn.2005.04.007}} @article{Zhai:2003, Abstract = {Local axon degeneration is a common pathological feature of many neurodegenerative diseases and peripheral neuropathies. While it is believed to operate with an apoptosis-independent molecular program, the underlying molecular mechanisms are largely unknown. In this study, we used the degeneration of transected axons, termed "Wallerian degeneration," as a model to examine the possible involvement of the ubiquitin proteasome system (UPS). Inhibiting UPS activity by both pharmacological and genetic means profoundly delays axon degeneration both in vitro and in vivo. In addition, we found that the fragmentation of microtubules is the earliest detectable change in axons undergoing Wallerian degeneration, which among other degenerative events, can be delayed by proteasome inhibitors. Interestingly, similar to transected axons, degeneration of axons from nerve growth factor (NGF)-deprived sympathetic neurons could also be suppressed by proteasome inhibitors. Our findings suggest a possibility that inhibiting UPS activity may serve to retard axon degeneration in pathological conditions.}, Author = {Zhai, Qiwei and Wang, Jing and Kim, Anna and Liu, Qing and Watts, Ryan and Hoopfer, Eric and Mitchison, Timothy and Luo, Liqun and He, Zhigang}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cysteine Proteinase Inhibitors;Wallerian Degeneration;Peptide Fragments;Disease Models, Animal;24 Pubmed search results 2008;Immunohistochemistry;Leupeptins;Chelating Agents;Animals;Cells, Cultured;Research Support, U.S. Gov't, P.H.S.;Egtazic Acid;Cysteine Endopeptidases;Multienzyme Complexes;Calpain;Drug Interactions;Tubulin;Axons;Ubiquitin;Microtubules;Optic Nerve Injuries;Nerve Growth Factor;Comparative Study;Blotting, Western;Proteasome Endopeptidase Complex;Amino Acids;Benzimidazoles;Rats;Time Factors;Endopeptidases;Animals, Newborn;Optic Nerve;Cytoskeleton;Research Support, Non-U.S. Gov't;Ganglia, Sympathetic}, Medline = {22756941}, Month = {7}, Nlm_Id = {8809320}, Number = {2}, Organization = {Division of Neuroscience, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.}, Pages = {217-25}, Pii = {S089662730300429X}, Pubmed = {12873380}, Title = {Involvement of the ubiquitin-proteasome system in the early stages of wallerian degeneration}, Uuid = {244BA733-28BD-41A1-9F9D-99859A276D75}, Volume = {39}, Year = {2003}} @article{Zhang:2004b, Abstract = {OBJECTIVE: Vein graft disease involves neointimal smooth muscle cells, the origins of which are unclear. This study sought to characterize and quantitate vein graft infiltration by cells extrinsic to the graft in a mouse model of vein graft disease. METHODS AND RESULTS: Inferior vena cava-to-carotid artery interposition grafting between C57Bl/6 and congenic beta-galactosidase-expressing ROSA26 mice was performed. Vein grafts were harvested 6 weeks postoperatively and stained with X-gal. More than 60\%of neointimal cells derived from the recipient, and 50\%of these cells expressed smooth muscle alpha-actin. The distribution of donor and recipient-derived cells within this vein graft wall layer was distinctly focal, consistent with focal infiltration and expansion of progenitor cells. When bone marrow transplantation with congenic green fluorescent protein (GFP)-expressing cells was used in vein graft recipients 1 month before surgery, abundant GFP-expressing cells appeared in the media, but not the neointima, of mature grafts. Endothelial cells in mature grafts derived from graft-intrinsic and graft-extrinsic sources and were, in part, of bone marrow origin. CONCLUSIONS: Cells extrinsic to the graft, including bone marrow-derived cells, predominate during vein graft remodeling.}, Author = {Zhang, Lisheng and Freedman, Neil J. and Brian, Leigh and Peppel, Karsten}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1524-4636}, Journal = {Arterioscler Thromb Vasc Biol}, Keywords = {Cell Differentiation;Lac Operon;Cell Survival;Immunoenzyme Techniques;T-Lymphocyte Subsets;Green Fluorescent Proteins;Animals;Myocytes, Smooth Muscle;Genes, Reporter;Cell Movement;Research Support, U.S. Gov't, P.H.S.;Animals, Congenic;Cell Count;Carotid Artery, Common;Bone Marrow Transplantation;Mice, Inbred C57BL;Macrophages;Endothelial Cells;11 Glia;Anastomosis, Surgical;Vena Cava, Inferior;Graft Survival;Radiation Chimera;Cell Lineage;Stem Cells;Tunica Intima;Mice;Research Support, Non-U.S. Gov't;Microscopy, Fluorescence;Mice, Transgenic}, Month = {3}, Nlm_Id = {9505803}, Number = {3}, Organization = {Duke University Department of Medicine (Cardiology), Duke University Medical Center, Durham, NC 27710, USA.}, Pages = {470-6}, Pii = {01.ATV.0000116865.98067.31}, Pubmed = {14726410}, Title = {Graft-extrinsic cells predominate in vein graft arterialization}, Uuid = {4D48D83A-93C1-413A-A1A0-868BF502C8ED}, Volume = {24}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.ATV.0000116865.98067.31}} @article{Zhang:2002, Abstract = {Gap junctions represent an important mode of intercellular communication. Connexin 45 (Cx45) is a member of the connexin family that forms gap junctions between adjacent cells. In this study, we demonstrate the expression of Cx45 in the olfactory epithelium and olfactory bulb in adult mice. Reverse transcription polymerase chain reaction amplification of total RNA from mouse turbinates and olfactory bulb yielded cDNA fragments partially encoding for Cx45. In situ hybridization using Cx45 cRNA probes revealed that hybridization products were more abundant in the olfactory epithelial layer than in the lamina propria underneath the epithelium. In the olfactory epithelial layer, hybridization signals were relatively intense in a band spreading from the basal cell layer to 4/5 of the distance from the basal cell layer to the apical process. The distribution of cells positive for Cx45 mRNA is largely overlapping with that of cells expressing olfactory marker protein mRNA, indicating that a substantial number of mature olfactory neurons express Cx45 mRNA. In the olfactory bulb, cells with large nuclei in the mitral cell layer, presumably mitral cells, express Cx45 mRNA. Immunoblotting with an antibody recognizing Cx45 revealed a band at approximately 46 kDa in homogenates of mouse turbinates and olfactory bulb. Immunohistochemical studies showed fine immunoreactive puncta in the olfactory epithelium. Immunoreactivity was observed surrounding cell bodies and the proximal processes of mitral cells in the olfactory bulb. The data suggest that Cx45 is a neuronal connexin that is expressed in mature neurons in adult mice. Our study implicates a functional role for Cx45 in the olfactory system deserving future study.}, Author = {Zhang, C. and Restrepo, D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Brain Res}, Keywords = {I abstr;13 Olfactory bulb anatomy}, Number = {1}, Organization = {Department of Cellular and Structural Biology, Neuroscience Program and the Rocky Mountain Taste and Smell Center, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, 80262, Denver, CO, USA}, Pages = {37-47.}, Title = {Expression of connexin 45 in the olfactory system}, Uuid = {CABB22D7-D44D-4212-A563-DDF919991DE1}, Volume = {929}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=11852029}} @article{Zhang:2004a, Abstract = {Directed migration of oligodendrocyte precursor cells (OPCs) is important for myelin formation and repair but the mechanisms of directional control are poorly understood. Here we have tested the role of polysialic acid-neural cell adhesion molecule (PSA-NCAM) in the directional migration of OPCs towards platelet-derived growth factor (PDGF). Using a Boyden microchemotaxis chamber and the Dunn direct viewing chamber, we show that in concentration gradients of PDGF, PSA-positive OPCs polarize and efficiently migrate towards the source of PDGF (chemotaxis). The loss or inactivation of the polysialic tail of NCAM leads to an altered pattern of OPC migration in response to PDGF gradients. Cells under these conditions, while being polarized and migrating, show no bias of displacement towards the source of PDGF and make random turns. By contrast, directed migration of OPCs towards basic fibroblast growth factor was not affected by the removal of PSA. Moreover, inactivation of PSA does not interfere with the random migration pattern of cells in uniform concentrations of PDGF (chemokinesis). These results suggest that PSA-NCAM is specifically involved in establishing the directionality of OPC migration in response to the concentration gradient of PDGF, but it is not essential for cell motility per se.}, Author = {Zhang, H. and Vutskits, L. and Calaora, V. and Durbec, P. and Kiss, J. Z.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0021-9533}, Journal = {J Cell Sci}, Keywords = {24 Pubmed search results 2008;Platelet-Derived Growth Factor;Cell Differentiation;Research Support, Non-U.S. Gov't;Neural Cell Adhesion Molecule L1;Myelin Sheath;Rats;Pseudopodia;Stem Cells;Cells, Cultured;Oligodendroglia;Chemotaxis;Sialic Acids;Animals}, Month = {1}, Nlm_Id = {0052457}, Number = {Pt 1}, Organization = {Department of Morphology, University of Geneva Medical School, 1 rue Michel Servet, CH-1211 Geneva 4, Switzerland.}, Pages = {93-103}, Pii = {jcs.00827}, Pubmed = {14627627}, Title = {A role for the polysialic acid-neural cell adhesion molecule in PDGF-induced chemotaxis of oligodendrocyte precursor cells}, Uuid = {9C389EE9-CA42-41B6-B565-49C814DDC37C}, Volume = {117}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/jcs.00827}} @article{Zhang:2002a, Abstract = {Murine sclerodermatous graft-vs-host disease (Scl GVHD) models human scleroderma, with prominent skin thickening, lung fibrosis, and up-regulation of cutaneous collagen mRNA. Fibrosis in Scl GVHD may be driven by infiltrating TGF-beta1-producing mononuclear cells. Here we characterize the origin and types of those cutaneous effector cells, the cytokine and chemokine environments, and the effects of anti-TGF-beta Ab on skin fibrosis, immune cell activation markers, and collagen and cytokine synthesis. Donor cells infiltrating skin in Scl GVHD increase significantly at early time points post-transplantation and are detectable by PCR analysis of Y-chromosome sequences when female mice are transplanted with male cells. Cutaneous monocyte/macrophages and T cells are the most numerous cells in Scl GVHD compared with syngeneic controls. These immune cells up-regulate activation markers (MHC class II I-A(d) molecules and class A scavenger receptors), suggesting Ag presentation by cutaneous macrophages in early fibrosing disease. Early elevated cutaneous mRNA expression of TGF-beta1, but not TGF-beta2 or TGF-beta3, and elevated C-C chemokines macrophage chemoattractant protein-1, macrophage inflammatory protein-1alpha, and RANTES precede subsequent skin and lung fibrosis. Therefore, TGF-beta1-producing donor mononuclear cells may be critical effector cells, and C-C chemokines may play important roles in the initiation of Scl GVHD. Abs to TGF-beta prevent Scl GVHD by effectively blocking the influx of monocyte/macrophages and T cells into skin and by abrogating up-regulation of TGF-beta1, thereby preventing new collagen synthesis. The Scl GVHD model is valuable for testing new interventions in early fibrosing diseases, and chemokines may be new potential targets in scleroderma.}, Author = {Zhang, Yan and McCormick, Laura L. and Desai, Snehal R. and Wu, Caiyun and Gilliam, Anita C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0022-1767}, Journal = {J Immunol}, Keywords = {Macrophage Inflammatory Protein-1;Cell Migration Inhibition;RANTES;Immune Sera;Disease Models, Animal;Male;Antigens, CD45;Up-Regulation;Lymphocyte Activation;Chemokines;Transforming Growth Factor beta;Animals;Research Support, U.S. Gov't, P.H.S.;Cell Movement;Macrophage-1 Antigen;Mice, Inbred BALB C;Bone Marrow Transplantation;Mice, Inbred C57BL;RNA, Messenger;Receptors, Immunologic;Skin;Macrophages;T-Lymphocytes;Graft vs Host Disease;Spleen;Histocompatibility Antigens Class II;Macrophage Activation;Collagen Type I;11 Glia;Receptors, Lipoprotein;Scleroderma, Systemic;Female;Membrane Proteins;Cytokines;Monocytes;Mice;Monocyte Chemoattractant Protein-1;Research Support, Non-U.S. Gov't;Humans}, Medline = {21881787}, Month = {3}, Nlm_Id = {2985117R}, Number = {6}, Organization = {Department of Dermatology, Case Western Reserve University/University Hospitals of Cleveland, Cleveland, OH 44106, USA.}, Pages = {3088-98}, Pubmed = {11884483}, Title = {Murine sclerodermatous graft-versus-host disease, a model for human scleroderma: cutaneous cytokines, chemokines, and immune cell activation}, Uuid = {8C05622D-5959-4E67-BF99-0124B2CAD0AA}, Volume = {168}, Year = {2002}} @article{Zhang:2004c, Abstract = {The orientation of mitotic cleavage regulates neurogenesis during neural development. We examined the orientation of mitotic cleavage of dividing progenitor cells in the subventricular zone (SVZ) of adult rats subjected to stroke. In nonstroke rats, 55\%of dividing cells were oriented horizontally, whereas 40\%were oriented vertically. Horizontal and vertical cleavage orientations produce asymmetric and symmetric divisions, respectively. Four days after stroke, the number of dividing cells increased twofold, whereas the proportion of symmetric dividing cells significantly (p <0.01) increased from 40\%before stroke to 60\%. Fourteen days after stroke, the percentage of symmetric dividing cells was 47\%. Stroke-increased numbers of dividing cells in M-phase were confirmed by immuostaining. In nonstroke rats, 37 and 33\%of symmetric and asymmetric dividing cells, respectively, exhibited a neuronal marker (TuJ1). Four days after stroke, rats exhibited a significant (p <0.05) augmentation of the frequency (47\%) of neuronal distribution showing TuJ1 immunoreactivity in cells with symmetric division but not cells with asymmetric division (33\%). Numb immunoreactivity was detected in SVZ cells of nonstroke rats. Stroke did not change Numb distribution. Our data suggest that neurons are produced by both asymmetric and symmetric cell divisions in the adult SVZ, and the transient increases in symmetric division and neuronal differentiation may result in stroke-induced neurogenesis.}, Author = {Zhang, Ruilan and Zhang, Zhenggang and Zhang, Chunling and Zhang, Li and Robin, Adam and Wang, Ying and Lu, Mei and Chopp, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cerebrovascular Accident;Cell Differentiation;Indicators and Reagents;Rats;Immunohistochemistry;Nerve Tissue Proteins;Stem Cells;Research Support, U.S. Gov't, P.H.S.;Time Factors;Rats, Wistar;06 Adult neurogenesis injury induced;Mitosis;Animals;Bromodeoxyuridine;Cerebral Ventricles;Neurons;Male}, Month = {6}, Nlm_Id = {8102140}, Number = {25}, Organization = {Department of Neurology, Henry Ford Health Sciences Center, Detroit, Michigan 48202, USA.}, Pages = {5810-5}, Pii = {24/25/5810}, Pubmed = {15215303}, Title = {Stroke transiently increases subventricular zone cell division from asymmetric to symmetric and increases neuronal differentiation in the adult rat}, Uuid = {70519FDF-C3FB-47F1-A3A4-27439870B99D}, Volume = {24}, Year = {2004}, url = {papers/Zhang_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1109-04.2004}} @article{Zhang:1997, Abstract = {We have characterized the cellular localization of stem cell factor (SCF) and c-kit receptor (c-kitR) in the adult mouse nervous system in situ and in culture by using immunocytochemistry. We found that SCF is largely confined to the neuronal population in normal brain, whereas c-kitR is expressed by glial cells as well as some neurons. We also found that astroglia at an early stage of culture (7 days in vitro) are strongly SCF positive and weakly c-kitR positive. Microglia in cultures express both SCF and c-kitR, but the immunostaining of SCF is weak and diffuse when microglia are cultured in the presence of colony stimulating factor-1. Northern blot analysis confirmed the expression of mRNAs of c-kit and SCF in cultured neurons, astroglia, and microglia. The addition of recombinant SCF to astroglia in culture upregulates the expression of mRNAs of nerve growth factor, brain derived neurotrophic factor, and ciliary neurotrophic factor. These observations suggest that SCF/c-kitR signaling is involved in neuron-neuron as well as neuron-glia interactions.}, Author = {Zhang, S. C. and Fedoroff, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Proto-Oncogene Protein c-kit;Animals;Astrocytes;Cells, Cultured;Ganglia, Spinal;Nervous System;Microglia;Mice, Inbred C3H;RNA, Messenger;11 Glia;Spinal Cord;Prosencephalon;Olfactory Bulb;Support, Non-U.S. Gov't;Blotting, Northern;Antibody Specificity;Cerebral Cortex;Neurons;Cerebellum;Mice;Stem Cell Factor;Immunohistochemistry;Brain Stem;Gene Expression;Peripheral Nerves}, Medline = {97135696}, Month = {1}, Nlm_Id = {7600111}, Number = {1}, Organization = {Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.}, Pages = {1-15}, Pii = {10.1002/(SICI)1097-4547(19970101)47:1<1::AID-JNR1>3.0.CO;2-N}, Pubmed = {8981233}, Title = {Cellular localization of stem cell factor and c-kit receptor in the mouse nervous system}, Uuid = {D1CB18FE-CB7B-42FE-916D-95952C3EFA3B}, Volume = {47}, Year = {1997}} @article{Zhang:2003a, Abstract = {Microglia are prominently involved in neural degenerative diseases of the CNS and the retina. In this study, we determined the activation and phagocytotic function of different subtypes of retinal microglial cells at 1 week and 1 month following optic axotomy. Fluorescent DiI crystals were placed at the stumps of the cut optic nerves of Lewis rats to retrolabel retinal ganglion cells. Microglial cells were indirectly labeled as they phagocytosed the dye particles in the dying ganglion cells. OX-42, 5D4, ED1, and OX-6 antibodies were used for immunohistochemical study. The OX-42- and 5D4-positive microglial cells were increased in the inner retinal layers after optic axotomy. The increase of OX-42-positive cells was considerably greater than that of 5D4-positive cells. The 5D4-positive cells were ramified in shape, whereas OX-42-positive cells were ameboid and ovoid. Both 5D4- and OX-42-positive cells phagocytosed dying ganglion cells at 1 week and 1 month after axotomy. Scattered ameboid ED1-positive cells were detected in the normal retina and showed phagocytotic activity at 1 month after optic axotomy. The number of ED1-positive cells in the retina was unchanged after axotomy. In optic axotomy, three types of microglial cells were activated, namely, 5D4-positive ramified cells and OX-42- and ED1-positive ameboid cells. All of them exhibited the phagocytosis of dying ganglion cells. Insofar as the blood-retinal barrier presumably remained intact in optic axotomy, the OX-42- and 5D4-positive cells might derive from resident microglial cells. The ED1-positive cells, presumably recently blood-borne macrophage in the CNS, remained the same number in the axotomized retina.}, Author = {Zhang, Cheng and Tso, Mark O. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Microscopy, Confocal;Retina;Membrane Glycoproteins;Indoles;Case-Control Studies;Rats;Comparative Study;Time Factors;Not relevant;Cell Count;11 Glia;Microglia;Optic Nerve Injuries;Optic Nerve;Amino Acids;Animals;Axotomy}, Medline = {22830189}, Month = {9}, Nlm_Id = {7600111}, Number = {6}, Organization = {Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9238, USA. czhang1\@jhmi.edu}, Pages = {840-5}, Pubmed = {12949910}, Title = {Characterization of activated retinal microglia following optic axotomy}, Uuid = {43A6A6A0-44FF-4863-B22E-1F72D80337A8}, Volume = {73}, Year = {2003}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.10713}} @article{Zhang:1994, Abstract = {The envelope glycoprotein G of vesicular stomatitis virus induces membrane fusion at low pH. Site-directed mutagenesis of specific amino acids within a segment spanning amino acids 123 to 137 of G protein, which is highly conserved in vesiculoviruses and was previously shown by us to be involved in fusogenic activity (Y. Li, C. Drone, E. Sat, and H. P. Ghosh, J. Virol. 67:4070-4077, 1993), was used to determine the role of this region in low-pH-induced membrane fusion. The mutant glycoproteins expressed in COS cells were assayed for acid-pH-induced cell-cell fusion. Substitution of the variant Pro-123 with Leu had no effect on the fusogenic activity, while substitution of conserved Phe-125 and Asp-137 with Tyr and Asn, respectively, shifted the pH optimum of membrane fusion to a more acidic pH value and decreased the fusion efficiency. The deletion of amino acid residues 124 to 127, 131 to 137, or 124 to 137 produced mutants defective in transport. Mutation of the conserved residues Gly-124 and Pro-127 to Ala and to Gly or Leu, respectively, inhibited cell-cell fusion activity by about 90\%without affecting transport of the mutant proteins to the cell surface, suggesting that these two residues may be present within the fusion peptide and thus may be directly involved in fusion. This highly conserved domain containing neutral amino acids of G protein may therefore represent the putative fusion domain of vesicular stomatitis virus G protein.}, Author = {Zhang, L. and Ghosh, H. P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Glycoproteins;Research Support, Non-U.S. Gov't;Conserved Sequence;Base Sequence;Sequence Homology, Amino Acid;Biological Transport;Protein Folding;Recombinant Proteins;Vesicular stomatitis-Indiana virus;15 Retrovirus mechanism;Cell Fusion;Glycosylation;Hydrogen-Ion Concentration;Viral Envelope Proteins;Protein Conformation;Membrane Glycoproteins;Cell Compartmentation;Amino Acid Sequence;24 Pubmed search results 2008;Molecular Sequence Data;Structure-Activity Relationship;Mutagenesis, Insertional}, Medline = {94187058}, Month = {4}, Nlm_Id = {0113724}, Number = {4}, Organization = {Department of Biochemistry, McMaster University, Hamilton, Ontario, Canada.}, Pages = {2186-93}, Pubmed = {8139003}, Title = {Characterization of the putative fusogenic domain in vesicular stomatitis virus glycoprotein G}, Uuid = {3C4CE65A-EE2C-11DA-8605-000D9346EC2A}, Volume = {68}, Year = {1994}} @article{Zhang:2003b, Abstract = {ts1 is a temperature-sensitive mutant of Moloney murine leukemia virus that induces a rapid spongiform encephalopathy in mice infected as newborns. The pathological features include the formation of ubiquitinated inclusions resembling Lewy bodies. To determine how perturbation of the ubiquitin-proteasome pathway might affect ts1-mediated neurodegeneration, the virus was introduced into transgenic mice in which the assembly of ubiquitin chains was compromised by the expression of dominant-negative mutant ubiquitin. The onset of symptoms was greatly delayed in a transgenic mouse line expressing K48R mutant ubiquitin; no such delay was observed in mice expressing a wild-type ubiquitin transgene or K63R mutant ubiquitin. The extended latency was found to correlate with a delayed increase in viral titers. Pathological findings in K48R transgenic mice at 60 days were found to be similar to those in the other strains at 30 days, suggesting that while delayed, the neurodegenerative process in K48R mice was otherwise similar. These data demonstrate the sensitivity of retroviral replication to the partial disruption of ubiquitin-mediated proteolysis in vivo, a finding that may have therapeutic potential.}, Author = {Zhang, Mei and Thurig, Sherry and Tsirigotis, Maria and Wong, Paul K. Y. and Reuhl, Kenneth R. and Gray, Douglas A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0022-538X}, Journal = {J Virol}, Keywords = {Mutation;Moloney murine leukemia virus;Not relevant;11 Glia;Mice, Transgenic;Support, U.S. Gov't, P.H.S.;Ubiquitin;Mice;Brain;Support, Non-U.S. Gov't;Animals}, Medline = {22689657}, Month = {7}, Nlm_Id = {0113724}, Number = {13}, Organization = {Centre for Cancer Therapeutics, Ottawa Regional Cancer Centre, Ottawa, Ontario, Canada K1H 1C4.}, Pages = {7193-201}, Pubmed = {12805418}, Title = {Effects of mutant ubiquitin on ts1 retrovirus-mediated neuropathology}, Uuid = {93B41BA1-376E-4066-A320-1B0AE3EEF014}, Volume = {77}, Year = {2003}, url = {papers/Zhang_JVirol2003.pdf}} @article{Zhang:2001, Abstract = {A distinct feature of the nervous system is the intricate network of synaptic connections among neurons of diverse phenotypes. Although initial connections are formed largely through molecular mechanisms that depend on intrinsic developmental programs, spontaneous and experience-driven electrical activities in the developing brain exert critical epigenetic influence on synaptic maturation and refinement of neural circuits. Selective findings discussed here illustrate some of our current understanding of the effects of electrical activity on circuit development and highlight areas that await further study.}, Author = {Zhang, L. I. and Poo, M. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {Synapses;10 Development;Central Nervous System;Cell Communication;Human;review, academic;Neural Pathways;Action Potentials;Growth Cones;Body Patterning;Animals;review;Nerve Growth Factors}, Medline = {21547545}, Month = {11}, Nlm_Id = {9809671}, Organization = {Keck Center of Integrative Neuroscience, University of California, San Francisco, California 94143-0732, USA.}, Pages = {1207-14}, Pii = {nn753}, Pubmed = {11687831}, Title = {Electrical activity and development of neural circuits}, Uuid = {E4C8A7B6-2370-4C08-83F3-FD6E5A81A735}, Volume = {4 Suppl}, Year = {2001}, url = {papers/Zhang_NatNeurosci2001.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn753}} @article{Zhang:2001b, Abstract = {Neuroglia are non-neuronal cells in the nervous system and are involved in virtually every aspect of neural function. Because of the ambiguity of glial function, the definition of glial cells relies chiefly on structural and biochemical characteristics. The use of molecular markers in identifying glial cells along their differentiation pathways is further complicated by recent findings that many of the molecules are also expressed by cells of the neuronal lineage. So, how specific are glial markers and how can a glial cell be defined during development?}, Author = {Zhang, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Nat Rev Neurosci}, Keywords = {10 Development;F pdf}, Number = {11}, Organization = {Su-Chun Zhang is at the Department of Anatomy and the Waisman Center, University of Wisconsin, 1500 Highland Avenue, Madison, Wisconsin 53705, USA.zhang\@waisman.wisc.edu}, Pages = {840-3.}, Title = {Defining glial cells during CNS development}, Uuid = {BC4B8B68-096D-4362-AA06-6AA06336A00B}, Volume = {2}, Year = {2001}, url = {papers/Zhang_NatRevNeurosci2001.pdf}} @article{Zhang:2007, Abstract = {Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.}, Author = {Zhang, Feng and Wang, Li-Ping P. and Brauner, Martin and Liewald, Jana F. and Kay, Kenneth and Watzke, Natalie and Wood, Phillip G. and Bamberg, Ernst and Nagel, Georg and Gottschalk, Alexander and Deisseroth, Karl}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Technique; frontiers review; optical physiology; optical imaging; activity manipulation}, Month = {4}, Nlm_Id = {0410462}, Number = {7136}, Organization = {Department of Bioengineering, Stanford University, Stanford, California 94305, USA.}, Pages = {633-9}, Pii = {nature05744}, Pubmed = {17410168}, Title = {Multimodal fast optical interrogation of neural circuitry}, Uuid = {3265C9FB-A1CD-4E44-B471-1BF2BD842BAF}, Volume = {446}, Year = {2007}, url = {papers/Zhang_Nature2007.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature05744}} @article{Zhang:2001a, Abstract = {Progenitor cells in the subventricular zone of the lateral ventricle and in the dentate gyrus of the hippocampus can proliferate throughout the life of the animal. To examine the proliferation and fate of progenitor cells in the subventricular zone and dentate gyrus after focal cerebral ischemia, we measured the temporal and spatial profiles of proliferation of cells and the phenotypic fate of proliferating cells in ischemic brain in a model of embolic middle cerebral artery occlusion in the adult rat. Proliferating cells were labeled by injection of bromodeoxyuridine (BrdU) in a pulse or a cumulative protocol. To determine the temporal profile of proliferating cells, ischemic rats were injected with BrdU every 4 h for 12 h on the day preceding death. Rats were killed 2-14 days after ischemia. We observed significant increases in numbers of proliferating cells in the ipsilateral cortex and subventricular zone 2-14 days with a peak at 7 days after ischemia compared with the control group. To maximize labeling of proliferating cells, a single daily injection of BrdU was administered over a 14-day period starting the day after ischemia. Rats were killed either 2 h or 28 days after the last injection of BrdU. A significant increase in numbers of BrdU immunoreactive cells in the subventricular zone was coincident with a significant increase in numbers of BrdU immunoreactive cells in the olfactory bulb 14 days after ischemia and numbers of BrdU immunoreactive cells did not significantly increase in the dentate gyrus. However, 28 days after the last labeling, the number of BrdU labeled cells decreased by 90\%compared with number at 14 days. Clusters of BrdU labeled cells were present in the cortex distal to the infarction. Numerous cells immunostained for the polysialylated form of the neuronal cell adhesion molecule were detected in the ipsilateral subventricular zone. Only 6\%of BrdU labeled cells exhibited glial fibrillary acidic protein immunoreactivity in the cortex and subcortex and no BrdU labeled cells expressed neuronal protein markers (neural nuclear protein and microtubule associated protein-2). From these data we suggest that focal cerebral ischemia induces transient and regional specific increases in cell proliferation in the ipsilateral hemisphere and that proliferating progenitor cells may exist in the adult cortex.}, Author = {Zhang, R. L. and Zhang, Z. G. and Zhang, L. and Chopp, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Neural Cell Adhesion Molecules;Glial Fibrillary Acidic Protein;Cell Differentiation;Animals;Microtubule-Associated Proteins;Rats;Recovery of Function;Rats, Wistar;Male;Antimetabolites;Nerve Regeneration;Research Support, U.S. Gov't, P.H.S.;Sialic Acids;Cerebral Cortex;Neurons;Brain Ischemia;Age Factors;Cell Division;24 Pubmed search results 2008;Immunohistochemistry;Stem Cells;Bromodeoxyuridine;Lateral Ventricles;Neural Cell Adhesion Molecule L1}, Medline = {21376613}, Nlm_Id = {7605074}, Number = {1}, Organization = {Department of Neurology, Henri Ford Health Sciences Center, Detroit, MI 48202, USA.}, Pages = {33-41}, Pii = {S0306452201001178}, Pubmed = {11483298}, Title = {Proliferation and differentiation of progenitor cells in the cortex and the subventricular zone in the adult rat after focal cerebral ischemia}, Uuid = {7217B296-89E9-4C04-B17A-500BC7A692FF}, Volume = {105}, Year = {2001}} @article{Zhang:2004, Abstract = {Long-term GABA(A) receptor alterations occur in hippocampal dentate granule neurons of rats that develop epilepsy after status epilepticus in adulthood. Hippocampal GABA(A) receptor expression undergoes marked reorganization during the postnatal period, however, and the effects of neonatal status epilepticus on subsequent GABA(A) receptor development are unknown. In the current study, we utilize single cell electrophysiology and antisense mRNA amplification to determine the effect of status-epilepticus induced by lithium-pilocarpine in postnatal day 10 rat pups on GABA(A) receptor subunit expression and function in hippocampal dentate granule neurons. We find that rats subjected to lithium-pilocarpine-induced status epilepticus at postnatal day 10 show long-term GABA(A) receptor changes including a two-fold increase in alpha1 subunit expression (compared with lithium-injected controls) and enhanced type I benzodiazepine augmentation that are opposite of those seen after status epilepticus in adulthood and may serve to enhance dentate gyrus inhibition. Further, unlike adult rats, postnatal day 10 rats subjected to status epilepticus do not become epileptic. These findings suggest age-dependent differences in the effects of status epilepticus on hippocampal GABA(A) receptors that could contribute to the selective resistance of the immature brain to epileptogenesis.}, Author = {Zhang, G. and Raol, Y. H. and Hsu, F-C C. and Coulter, D. A. and Brooks-Kayal, A. R.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {Cell Survival;Dose-Response Relationship, Drug;Pilocarpine;Animals;Gene Expression Regulation;In Vitro;Rats;Comparative Study;21 Epilepsy;Patch-Clamp Techniques;Rats, Sprague-Dawley;Hippocampus;RNA, Messenger;Video Recording;Lithium Chloride;Reverse Transcriptase Polymerase Chain Reaction;Status Epilepticus;Pyridines;Research Support, U.S. Gov't, P.H.S.;Receptors, GABA-A;Blotting, Northern;Cerebral Cortex;Animals, Newborn;21 Neurophysiology;Age Factors;24 Pubmed search results 2008;Drug Interactions;Electroencephalography;GABA Agonists}, Nlm_Id = {7605074}, Number = {2}, Organization = {Division of Neurology, Pediatric Regional Epilepsy Program, Children's Hospital of Philadelphia, Philadelphia, PA, USA.}, Pages = {299-303}, Pii = {S0306452204000958}, Pubmed = {15062973}, Title = {Effects of status epilepticus on hippocampal GABAA receptors are age-dependent}, Uuid = {5A6D2649-ACD8-4988-9D84-D399165095F8}, Volume = {125}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2004.01.040}} @article{Zhang:1995, Abstract = {Prenatal exposure to several neuroteratogens, such as ionizing radiation, ethanol, and cytotoxic drugs, induces the development of clusters of abnormally positioned neurons within the brain. These abnormalities have always been presumed to result from interference with normal neuronal migration, presumably via effects on radial glia. In our study, pregnant rats were injected with methylazoxymethanol acetate (MAM) on either E13, E14, or E15. Computerised reconstruction techniques, Golgi and immunocytochemical staining as well as electron microscopy were used to detect structural abnormalities of radial glia which might be responsible for the production of heterotopiae. Several structural abnormalities such as microcavitation, involvement of radial glial elements in rosettes, disturbance of the normal ventricular lining, and disruption of the attachment of radial glial endfeet to the pial surface were identified. We propose that periventricular heterotopiae result from disruption of the palisade arrangement of neuroepithelial cells in the ventricular zone and the involvement of radial glial elements in rosettes. Layer I heterotopiae may arise from abnormalities of the distal segments of radial glia and their attachment to the pia. No prenatal abnormalities in radial glia of the hippocampus were noted following MAM exposure at any of the 3 ages, consistent with the proposition that hippocampal heterotopiae arise by postnatal movements of pyramidal neurons without radial glial involvement.}, Author = {Zhang, L. L. and Collier, P. A. and Ashwell, K. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0892-0362}, Journal = {Neurotoxicol Teratol}, Keywords = {10 Development;Pregnancy;Animals;Image Processing, Computer-Assisted;Rats;Female;Staining and Labeling;Pyramidal Cells;research support, non-u.s. gov't;Rats, Wistar;Paraffin Embedding;Prosencephalon;Teratogens;10 genetics malformation;Neuroglia;Methylazoxymethanol Acetate;Neurons;Prenatal Exposure Delayed Effects;24 Pubmed search results 2008;Immunohistochemistry;Brain Damage, Chronic;Microscopy, Electron}, Nlm_Id = {8709538}, Number = {3}, Organization = {School of Anatomy, University of NSW, Sydney, Australia.}, Pages = {297-311}, Pii = {089203629400072L}, Pubmed = {7542736}, Title = {Mechanisms in the induction of neuronal heterotopiae following prenatal cytotoxic brain damage}, Uuid = {8B0DBA3C-ECBC-4BF8-89A3-9914F71FE730}, Volume = {17}, Year = {1995}} @article{Zhang:2005, Abstract = {Vernier acuity is a measure of the smallest horizontal offset between two vertical lines that can be behaviorally discriminated. To examine the link between the neuronal responses in a retinotopic mosaic and vernier acuity, we recorded the responses of single cells in cat lateral geniculate nucleus to a vertical bar stimulus that was stepped in small increments through the receptive fields of cells. Based on the single-trial responses evoked by stimuli at different positions, we calculated the spatial resolution that could be achieved. If the stimulus could fall anywhere in their receptive fields, single neurons had spatial resolutions two times worse than previously reported vernier thresholds. Given the known coverage factor in a cat retina, we developed a two-stage decision model to examine how the responses of neurons in a retinotopic mosaic could be processed to achieve vernier acuity. In order for psychophysical thresholds to be accounted for by the responses of a single cell, the stimulus must fall in the quarter of the receptive field that provides the most information about stimulus position. Alternatively, both the absolute psychophysical threshold for vernier acuity and its dependence on stimulus length can be realized by pooling the responses of a few neurons, all located on one side of the bar stimulus.}, Author = {Zhang, Ying and Reid, R. Clay}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {research support, u.s. gov't, p.h.s. ;21 Neurophysiology;Cats;Action Potentials;Animals;24 Pubmed search results 2008;Neurons}, Month = {3}, Nlm_Id = {7505876}, Number = {9}, Organization = {Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.}, Pages = {3507-12}, Pii = {0409914102}, Pubmed = {15728369}, Title = {Single-neuron responses and neuronal decisions in a vernier task}, Uuid = {C60B37ED-FFE3-446F-A0A4-D4AAA68AEC2E}, Volume = {102}, Year = {2005}, url = {papers/Zhang_ProcNatlAcadSciUSA2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0409914102}} @article{Zhang:2003, Abstract = {OBJECTIVE: To investigate the proliferation and differentiation of neural stem cells after cerebral infarction(CI) in adult rats. METHODS: CI animal model was made by ligating the common carotid artery and external carotid artery and inserting a piece of nylon thread into the internal carotid artery among 100 male Wistar rats. Then the rats were randomly divided into 5 groups: group of I day after brain infarction (n = 20), group of 3 days after brain infarction (n = 20), group of 7 days after brain infarction (n = 20), group of 14 days after brain infarction (n = 20), and group of 28 days after brain infarction (n = 20). Twelve rats undergoing sham operation with a piece of nylon thread inserted only into the common carotid artery were used as controls. The rats were killed at different time points and their brains were taken out. The expression of bromodeoxyuridine (BrdU) and Musashil (both used to mark the dividing neural stem cells), and of glial fibrillary acidic protein (GFAP) and neuronal nuclear antigen (NeuN) (both used to mark the differentiating neural stem cells) were determined by immunohistochemistry and immunofluorescence staining. RESULTS: In the normal brain tissues, only a small amount of BrdU(+) cells were found in the hippocampus. One day after CI the number of BrdU(+) cells began to increase in the hippocampus at the CI side (P < 0.05), peaked 7 days after CI with a number 6 times that at the normal side, began to decrease 14 days after, and almost reached normal 28 days after. The number of BrdU(+)/Musashil(+) cells began to increase 1 day after CI (P < 0.05), peaked 7 days after, began to decrease 14 days after, and almost reached normal 28 days after. The number of BrdU(+)/GFAP(+) cells at the CI side remained almost unchanged after CI. The number of BrdU(+)/NeuN(+) cells began to increase 14 days after CI (P < 0.05) and peaked 38 days after. CONCLUSION: Cerebral infarction stimulates the proliferation of inherent neural stem cells and most proliferated neural stem cells differentiate into neurons.}, Author = {Zhang, Bo and Wang, Ren-zhi Z. and Yao, Yong and Wang, Xin and Li, Gui-lin L. and Dou, Wan-chen C. and Tian, Shi-qiang Q. and Zheng, Tong and Tian, Yu}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0376-2491}, Journal = {Zhonghua Yi Xue Za Zhi}, Keywords = {Cell Differentiation;Research Support, Non-U.S. Gov't;Immunohistochemistry;Rats;English Abstract;Cell Division;Cerebral Infarction;Rats, Wistar;Stem Cells;Fluorescent Antibody Technique;Animals;Bromodeoxyuridine;24 Pubmed search results 2008;Male;Neurons}, Month = {11}, Nlm_Id = {7511141}, Number = {22}, Organization = {Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.}, Pages = {1975-9}, Pubmed = {14703433}, Title = {[Proliferation and differentiation of neural stem cells after cerebral infarction: an experimental study of adult rats]}, Uuid = {788227EB-7A23-463D-A8F8-8B3D3A094179}, Volume = {83}, Year = {2003}} @article{Zhao:2008, Abstract = {The generation of new neurons is sustained throughout adulthood in the mammalian brain due to the proliferation and differentiation of adult neural stem cells. In this review, we discuss the factors that regulate proliferation and fate determination of adult neural stem cells and describe recent studies concerning the integration of newborn neurons into the existing neural circuitry. We further address the potential significance of adult neurogenesis in memory, depression, and neurodegenerative disorders such as Alzheimer's and Parkinson's disease.}, Author = {Zhao, Chunmei and Deng, Wei and Gage, Fred H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1097-4172}, Journal = {Cell}, Keywords = {Neurons;01 Adult neurogenesis general;Cell Differentiation;research support, non-u.s. gov't;24 Pubmed search results 2008;Stem Cells;research support, n.i.h., extramural;Animals;Brain;Humans;review;Nervous System Diseases}, Month = {2}, Nlm_Id = {0413066}, Number = {4}, Organization = {Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.}, Pages = {645-60}, Pii = {S0092-8674(08)00134-7}, Pubmed = {18295581}, Title = {Mechanisms and functional implications of adult neurogenesis}, Uuid = {738203B3-7794-4DDA-8CE5-F291210EC140}, Volume = {132}, Year = {2008}, url = {papers/Zhao_Cell2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.cell.2008.01.033}} @article{Zhao:2007a, Abstract = {The extracellular matrix protein reelin is essential for the proper radial migration of cortical neurons. In reeler mice lacking reelin, there is a malformation of the radial glial scaffold required for granule cell migration. Immunostaining for glial fibrillary acidic protein (GFAP) reveals abundant radial glial cells with long fibers traversing the granular layer in the wild type, but almost exclusively astrocytes in the reeler mutant. With the concept that radial glial cells are precursors of neurons, we hypothesized that the balance between neurogenesis and gliogenesis is altered in the reeler mutant. To this end, adult reeler mutants and their wild-type littermates were injected with bromodeoxyuridine (BrdU), a marker of newly generated cells. When compared to wild-type animals, we found a reduction in the number of BrdU-labeled cells in the adult reeler dentate gyrus. Moreover, whereas there was a dramatic decrease in the number of newly generated granule cells identified by double labeling for BrdU and NeuN, the number of BrdU-labeled, GFAP-positive astrocytes had increased. Decreased neurogenesis in the adult reeler dentate gyrus was confirmed by immunostaining for doublecortin, a marker of newly generated neurons. These results indicate that adult neurogenesis is altered in the reeler dentate gyrus and that newly generated cells preferentially differentiate into astrocytes.}, Author = {Zhao, Shanting and Chai, Xuejun and Frotscher, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0378-5866}, Journal = {Dev Neurosci}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Nlm_Id = {7809375}, Number = {1-2}, Organization = {Institut fur Anatomie und Zellbiologie, Albert-Ludwigs-Universitat Freiburg, Freiburg, Deutschland.}, Pages = {84-90}, Pii = {DNE20070291_2084}, Pubmed = {17148951}, Title = {Balance between neurogenesis and gliogenesis in the adult hippocampus: role for reelin}, Uuid = {DA576DA5-EB10-4FD1-B204-D7881C428AD4}, Volume = {29}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1159/000096213}} @article{Zhao:2004a, Abstract = {Reelin is required for the proper positioning of neurons in the cerebral cortex. In the reeler mutant lacking reelin, the granule cells of the dentate gyrus fail to form a regular, densely packed cell layer. Recent evidence suggests that this defect is due to the malformation of radial glial processes required for granule cell migration. Here, we show that recombinant reelin in the medium significantly increases the length of GFAP-positive radial glial fibers in slice cultures of reeler hippocampus, but does not rescue either radial glial fiber orientation or granule cell lamination. However, rescue of radial glial fiber orientation and granule cell lamination was achieved when reelin was present in the normotopic position provided by wild-type co-culture, an effect that is blocked by the CR-50 antibody against reelin. These results indicate a dual function of reelin in the dentate gyrus, as a differentiation factor for radial glial cells and as a positional cue for radial fiber orientation and granule cell migration.}, Author = {Zhao, Shanting and Chai, Xuejun and F{\"o}rster, Eckart and Frotscher, Michael}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0950-1991}, Journal = {Development}, Keywords = {Research Support, Non-U.S. Gov't;Extracellular Matrix Proteins;Rats;Dentate Gyrus;Animals;Cell Movement;Cell Adhesion Molecules, Neuronal;Neurons;Mice}, Month = {10}, Nlm_Id = {8701744}, Number = {20}, Organization = {Institute of Anatomy and Cell Biology, Albert-Ludwigs-Universit{\"a}t Freiburg, Albertstr. 17, 79104 Freiburg, Germany.}, Pages = {5117-25}, Pii = {131/20/5117}, Pubmed = {15459104}, Title = {Reelin is a positional signal for the lamination of dentate granule cells}, Uuid = {021B4122-716E-11DA-A383-000D9346EC2A}, Volume = {131}, Year = {2004}, url = {papers/Zhao_Development2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1242/dev.01387}} @article{Zhao:2004, Abstract = {The hippocampus develops from the medial wall of the forming cerebral cortex during embryonic life. Morphogenic signals from the Wnt pathway regulate several events during hippocampal development (Galceran et al.: Development 127:469-482, 2000; Lee et al.: Development 127:457-467, 2000; Zhou et al.: J Neurosci 24:121-126, 2004) and we have previously shown that Wnt receptors from the Frizzled (Fzd) family are expressed in discreet cortical domains during development (Kim et al.: Mech Dev 103:167-172, 2001). We generated transgenic mice using the putative control elements of the Fzd9 gene, normally selectively expressed in the developing and adult hippocampus, driving expression of a marker gene. These mice express LacZ in the brain in the same developmental distribution as endogenous Fzd protein. Postnatally, expression remains strong in the dendritic fields of hippocampal principal cells as well as hippocampal efferent axons. These mice provide a genetic and anatomic tool for analyzing development and reorganization in the hippocampus.}, Author = {Zhao, Chunjie and Pleasure, Samuel J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1526-954X}, Journal = {Genesis}, Keywords = {beta-Galactosidase;Animals;Cloning, Molecular;Base Sequence;Mice, Transgenic;Hippocampus;RNA, Messenger;DNA Primers;Peptide Fragments;Research Support, U.S. Gov't, P.H.S.;Cerebral Cortex;Receptors, Neurotransmitter;Promoter Regions (Genetics);Mice;Immunohistochemistry;Molecular Sequence Data;Amino Acid Sequence;Research Support, Non-U.S. Gov't}, Month = {9}, Nlm_Id = {100931242}, Number = {1}, Organization = {Department of Neurology, Programs in Neuroscience and Developmental Biology, University of California, San Francisco, California, USA.}, Pages = {32-9}, Pubmed = {15354291}, Title = {Frizzled-9 promoter drives expression of transgenes in the medial wall of the cortex and its chief derivative the hippocampus}, Uuid = {AD8B1299-A3E5-11DA-AB00-000D9346EC2A}, Volume = {40}, Year = {2004}, url = {papers/Zhao_Genesis2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/gene.20058}} @article{Zhao:1996, Abstract = {We used recombinant adenoviruses as a means of expressing exogenous genes in olfactory neurons in vivo. A replication incompetent adenovirus (type 5, Ad5) carrying the reporter gene lacZ, which codes for the enzyme beta-galactosidase (beta-Gal), was applied in solution to the olfactory epithelia of rats. The expression of lacZ was controlled by the cytomegalovirus immediate-early promoter/enhancer. beta-Gal expression was observed 1 day postinfection and was maximal at 3-10 days, although it could be detected for at least 21 days postinfection. Expression patterns were heterogeneous, ranging from a few percent to over 25\%of the cells in different regions of both turbinate and septal epithelium. Staining was stronger in the olfactory versus respiratory epithelia. In olfactory epithelium staining was almost entirely restricted to olfactory neurons. beta-Gal staining was also observed in the olfactory axons so that nerve bundles could be traced to their targets in the glomerular layer of the olfactory bulb. Intense staining of some glomeruli was evident as long as 21 days postinfection. There was no evidence of cell loss or tissue damage due to viral infection. These results demonstrate that it is possible to use recombinant Ad5 for expressing foreign genes in olfactory neurons. This technique could be used in olfactory neurons to increase expression levels of olfactory specific genes, including the odor receptor, putative guidance and growth molecules, or elements of the transduction cascade, in order to elucidate their biological functions in vivo.}, Author = {Zhao, H. and Otaki, J. M. and Firestein, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {J Neurobiol}, Keywords = {beta-Galactosidase/metabolism;Rats, Sprague-Dawley;*Adenoviridae;Lac Operon;Rats;Neurons, Afferent/*physiology;Animal;Support, U.S. Gov't, P.H.S.;I abstr;Olfactory Pathways/cytology/*physiology;Histocytochemistry;13 Olfactory bulb anatomy;*Gene Transfer Techniques}, Number = {4}, Organization = {Interdepartmental Neuroscience Program, Yale University, New Haven, Connecticut 06510, USA.}, Pages = {521-30.}, Title = {Adenovirus-mediated gene transfer in olfactory neurons in vivo}, Uuid = {65EF9FC7-4A4C-41D0-ACB9-8F7F8DF6D7AC}, Volume = {30}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=8844515}} @article{Zhao:2006, Abstract = {Adult neurogenesis in the dentate gyrus may contribute to hippocampus-dependent functions, yet little is known about when and how newborn neurons are functional because of limited information about the time course of their connectivity. By using retrovirus-mediated gene transduction, we followed the dendritic and axonal growth of adult-born neurons in the mouse dentate gyrus and identified distinct morphological stages that may indicate different levels of connectivity. Axonal projections of newborn neurons reach the CA3 area 10-11 d after viral infection, 5-6 d before the first spines are formed. Quantitative analyses show that the peak of spine growth occurs during the first 3-4 weeks, but further structural modifications of newborn neurons take place for months. Moreover, the morphological maturation is differentially affected by age and experience, as shown by comparisons between adult and postnatal brains and between housing conditions. Our study reveals the key morphological transitions of newborn granule neurons during their course of maturation.}, Author = {Zhao, Chunmei and Teng, E. Matthew and Summers, Robert G. and Ming, Guo-Li L. and Gage, Fred H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {01 Adult neurogenesis general;24 Pubmed search results 2008}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {3-11}, Pii = {26/1/3}, Pubmed = {16399667}, Title = {Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus}, Uuid = {BFA769B1-F8D3-479E-A9E6-B378AA68E45A}, Volume = {26}, Year = {2006}, url = {papers/Zhao_JNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3648-05.2006}} @article{Zhao:2005, Abstract = {CNS remyelination occurs more rapidly in young adult rats than in old rats. Since the inflammatory response initiated by demyelination is an important trigger for remyelination, we address whether ageing changes in remyelination are associated with changes in the inflammatory response. Using a toxin model of demyelination, where the inflammatory response largely comprises macrophages, we show that there is a delay in both recruitment and activation of OX-42+ and macrophage scavenger receptor B+ macrophages following demyelination in older rats (10-13 months) compared to young rats (8-10 weeks). This difference is associated with a slower onset of increased expression of several chemokine mRNAs. However, many inflammatory cytokines have similar mRNA expression patterns, with the exception of IL-1beta, IL-6 and TNF-alpha, which have prolonged expression in the older animals. Differences in IL-1beta mRNA expression, a cytokine specifically implicated in CNS remyelination, are not reflected in differences in protein expression detected by immunocytochemistry. These data relate the age-associated delay in remyelination efficiency to changes in the macrophage and inflammatory mediator response to demyelination.}, Author = {Zhao, and Li, and Franklin,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0197-4580}, Journal = {Neurobiol Aging}, Keywords = {11 Glia}, Month = {7}, Nlm_Id = {8100437}, Organization = {Cambridge Center for Brain Repair and Neuroregeneration Laboratory, Department of Veterinary Medicine, University of Cambridge, Cambridge CB3 0ES, UK.}, Pii = {S0197-4580(05)00183-1}, Pubmed = {16051398}, Title = {Differences in the early inflammatory responses to toxin-induced demyelination are associated with the age-related decline in CNS remyelination}, Uuid = {730A63EE-E4FF-4C47-AF53-74DD80CADF8A}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neurobiolaging.2005.06.008}} @article{Zhao:2007, Abstract = {Neural progenitor cells (NPCs) in the subventricular zone (SVZ) travel a long distance along the rostral migratory stream (RMS) to give rise to interneurons in the olfactory bulb (OB). Using the multiphoton microscope and time-lapse recording techniques we here report the behavior of NPCs in the RMS under both intact and ischemic conditions in living brain slices. The NPCs were visualized in 3-week-old transgenic mice that carry the reporter gene, green fluorescent protein (GFP), driven by the nestin promoter. Cortical brain ischemia was induced by permanent occlusion of the right common carotid artery and the middle cerebral artery. We observed that the RMS contained two populations of NPCs: nonmigrating cells (bridge cells) and migrating cells. Bridge cells enabled migrating cells to travel and also produced new cells in the RMS. The direction of NPC migration in the RMS was bidirectional in both intact and ischemic conditions. Cortical ischemia impeded NPC travel in the RMS next to the lesion area during the early period of ischemia. Cell-cell contact was a prominent feature affecting NPC translocation and migratory direction. These data suggest that behavior and function of nestin-positive NPCs in the RMS are variable. Cell-cell contacts and microenvironmental changes influence NPC behavior in the RMS. This study may provide insights to help in understanding NPC biology.}, Author = {Zhao, Li-Ru R. and Nam, Sang Chae}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0304-3940}, Journal = {Neurosci Lett}, Keywords = {research support, non-u.s. gov't;24 Pubmed search results 2008}, Month = {9}, Nlm_Id = {7600130}, Number = {2}, Organization = {Department of Neurology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA. lzhao\@lsuhsc.edu}, Pages = {83-8}, Pii = {S0304-3940(07)00775-6}, Pubmed = {17723276}, Title = {Multiphoton microscope imaging: the behavior of neural progenitor cells in the rostral migratory stream}, Uuid = {0B54556D-9CF1-481B-842B-4877C6AC091B}, Volume = {425}, Year = {2007}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neulet.2007.07.032}} @article{Zhao:2003, Abstract = {New neurons are generated from stem cells in a few regions of the adult mammalian brain. Here we provide evidence for the generation of dopaminergic projection neurons of the type that are lost in Parkinson's disease from stem cells in the adult rodent brain and show that the rate of neurogenesis is increased after a lesion. The number of new neurons generated under physiological conditions in substantia nigra pars compacta was found to be several orders of magnitude smaller than in the granular cell layer of the dentate gyrus of the hippocampus. However, if the rate of neuronal turnover is constant, the entire population of dopaminergic neurons in substantia nigra could be replaced during the lifespan of a mouse. These data indicate that neurogenesis in the adult brain is more widespread than previously thought and may have implications for our understanding of the pathogenesis and treatment of neurodegenerative disorders such as Parkinson's disease. 0027-8424 Journal Article}, Author = {Zhao, M. and Momma, S. and Delfani, K. and Carlen, M. and Cassidy, R. M. and Johansson, C. B. and Brismar, H. and Shupliakov, O. and Frisen, J. and Janson, A. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Human;Neurons/*metabolism/pathology;Animals;Synapses;Bromodeoxyuridine/pharmacology;Parkinson Disease/pathology;Stem Cells/metabolism;Dopamine Agents/pharmacology;Dopamine/metabolism;Hippocampus/pathology;Apoptosis;1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology;Mice, Inbred C57BL;Microscopy, Fluorescence;Male;Time Factors;01 Adult neurogenesis general;Substantia Nigra/*anatomy &histology/metabolism/*pathology;Antimetabolites/pharmacology;Mice;A pdf}, Number = {13}, Organization = {Departments of Neuroscience, Cell and Molecular Biology, Medical Nobel Institute, and Woman and Child Health, Karolinska Institute, SE-171 77 Stockholm, Sweden.}, Pages = {7925-30}, Pubmed = {12792021}, Title = {Evidence for neurogenesis in the adult mammalian substantia nigra}, Uuid = {973755E6-7347-4515-8D32-C66D3560A57C}, Volume = {100}, Year = {2003}, url = {papers/Zhao_ProcNatlAcadSciUSA2003.pdf}} @article{Zhao:2003a, Abstract = {DNA methylation-mediated epigenetic regulation plays critical roles in regulating mammalian gene expression, but its role in normal brain function is not clear. Methyl-CpG binding protein 1 (MBD1), a member of the methylated DNA-binding protein family, has been shown to bind methylated gene promoters and facilitate transcriptional repression in vitro. Here we report the generation and analysis of MBD1-/- mice. MBD1-/- mice had no detectable developmental defects and appeared healthy throughout life. However, we found that MBD1-/- neural stem cells exhibited reduced neuronal differentiation and increased genomic instability. Furthermore, adult MBD1-/- mice had decreased neurogenesis, impaired spatial learning, and a significant reduction in long-term potentiation in the dentate gyrus of the hippocampus. Our findings indicate that DNA methylation is important in maintaining cellular genomic stability and is crucial for normal neural stem cell and brain functions. 0027-8424 Journal Article}, Author = {Zhao, X. and Ueba, T. and Christie, B. R. and Barkho, B. and McConnell, M. J. and Nakashima, K. and Lein, E. S. and Eadie, B. D. and Willhoite, A. R. and Muotri, A. R. and Summers, R. G. and Chun, J. and Lee, K. F. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Cell Differentiation;Mice, Knockout;Neurons/cytology;Hippocampus/cytology/*physiology;C pdf;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;*CpG Islands;Support, Non-U.S. Gov't;Animals;DNA-Binding Proteins/*genetics;Mice}, Number = {11}, Organization = {Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.}, Pages = {6777-82}, Pubmed = {12748381}, Title = {Mice lacking methyl-CpG binding protein 1 have deficits in adult neurogenesis and hippocampal function}, Uuid = {15ED9CF0-E6BA-4963-B858-0ADBE7F7FD6B}, Volume = {100}, Year = {2003}, url = {papers/Zhao_ProcNatlAcadSciUSA2003a.pdf}} @article{Zharkovsky:2003, Abstract = {Administration of ethanol during brain development induces widespread neuronal loss in various structures of the brain. Here, we show that a single administration of ethanol given during the early postnatal period can induce not only neuronal death, but also an increase in proliferation of the progenitor cells in the dentate gyrus of hippocampal formation in rats. Ethanol (1.5 or 3 g/kg, i.p.) administered to 10-day-old rats induced massive neuronal degeneration as evidenced by TUNEL assay in the dentate gyrus. The neuronal death induced by a high dose of ethanol (3 g/kg) was accompanied by an enhanced proliferation of the progenitor cells labeled by bromodeoxyuridine (BrdU, 50 mg/kg, i.p.) in dentate gyrus. One and 3 weeks following ethanol or saline administration, ethanol-treated rats still had significantly more BrdU-labeled cells than control animals. In ethanol-treated rats, a higher proportion of newly born cells acquired the phenotype of immature postmitotic neurons whereas the final differentiation into calbindin-expressing granule cells remained unchanged. The proportion of astroglial cells was also increased in ethanol-treated rats. Thus, ethanol given in high doses not only induces neurodegeneration but also initiates the process of neuro- and gliogenesis, which might be responsible for the neuronal and glial reorganization of the dentate gyrus.}, Author = {Zharkovsky, Tamara and Kaasik, Allen and Jaako, K{\"u}lli and Zharkovsky, Alexander}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Research Support, Non-U.S. Gov't;Dose-Response Relationship, Drug;Nerve Degeneration;Ethanol;Animals;Rats;Comparative Study;Radiation-Sensitizing Agents;Central Nervous System Depressants;Cell Count;Hippocampus;Rats, Wistar;Animals, Newborn;Sialic Acids;In Situ Nick-End Labeling;Dentate Gyrus;Cell Division;Immunohistochemistry;24 Pubmed search results 2008;Bromodeoxyuridine;Neural Cell Adhesion Molecule L1;DNA Fragmentation;Regeneration}, Medline = {22718819}, Month = {7}, Nlm_Id = {0045503}, Number = {1-2}, Organization = {Department of Pharmacology, University of Tartu, 19 Ravila Street, 51014 Tartu, Estonia.}, Pages = {115-23}, Pii = {S0006899303027963}, Pubmed = {12834905}, Title = {Neurodegeneration and production of the new cells in the dentate gyrus of juvenile rat hippocampus after a single administration of ethanol}, Uuid = {6F368281-E8FE-45F2-8CC1-CE22B0E4057A}, Volume = {978}, Year = {2003}} @article{Zheng:2000, Abstract = {Nucleoside kinases from several species are investigated as "suicide genes" for treatment of malignant tumors by combined gene/chemotherapy. We have recently cloned a multisubstrate deoxyribonucleoside kinase of Drosophila melanogaster (Dm-dNK), and we have shown that the enzyme phosphorylates cytotoxic pyrimidine and purine nucleoside analogs. The broad substrate specificity of the enzyme, as well as its very high catalytic rate, makes it a unique member of the nucleoside kinase enzyme family. In the present study, we evaluated Dm-dNK as a suicide gene by constructing a replication-deficient retroviral vector that expresses the enzyme. The human pancreatic adenocarcinoma cell line MIA PaCa-2 and a thymidine kinase-deficient osteosarcoma cell line were transduced with the recombinant virus. We showed that Dm-dNK can be expressed in human cells, that the enzyme retained its enzymatic activity, and that it is localized in the cell nuclei due to a nuclear localization signal in its C-terminal region. The cells expressing Dm-dNK exhibited increased sensitivity to several cytotoxic nucleoside analogs, such as 1-beta-d-arabinofuranosylcytosine, 1-beta-d-arabinofuranosylthymine, (E)-5-(2-bromovinyl)-2'-deoxyuridine, 2-chloro-2'-deoxyadenosine, and 2',2'-difluorodeoxycytidine. These findings suggest that Dm-dNK may be used as a suicide gene in combined gene/chemotherapy of cancer.}, Author = {Zheng, X. and Johansson, M. and Karlsson, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0021-9258}, Journal = {J Biol Chem}, Keywords = {Inhibitory Concentration 50;Adenocarcinoma;24 Pubmed search results 2008;Drosophila melanogaster;Tumor Cells, Cultured;Thymidine Kinase;Transduction, Genetic;Animals;Cytarabine;Osteosarcoma;Arabinonucleosides;Kinetics;Cladribine;15 Retrovirus mechanism;Promoter Regions (Genetics);Bromodeoxyuridine;Phosphotransferases (Alcohol Group Acceptor);Cell Division;Substrate Specificity;Antimetabolites, Antineoplastic;Retroviridae;Pancreatic Neoplasms;Deoxycytidine;Cell Nucleus;Antineoplastic Agents;Thymidine;Research Support, Non-U.S. Gov't;Antiviral Agents;Humans;Phosphorylation;Catalysis}, Medline = {20564273}, Month = {12}, Nlm_Id = {2985121R}, Number = {50}, Organization = {Karolinska Institute, Division of Clinical Virology, Huddinge University Hospital, S-141 86 Stockholm, Sweden.}, Pages = {39125-9}, Pii = {M006212200}, Pubmed = {10993893}, Title = {Retroviral transduction of cancer cell lines with the gene encoding Drosophila melanogaster multisubstrate deoxyribonucleoside kinase}, Uuid = {84ADFAD7-4C2E-4AF1-A929-F5A51DE50289}, Volume = {275}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1074/jbc.M006212200}} @article{Zheng:2006, Abstract = {In the rodent hippocampus, the radial glial scaffold consists of radial glial cells (RGCs) and plays important roles in neurogenesis in this area after birth. However, the mechanisms that maintain the radial glial scaffold in the postnatal dentate gyrus (DG) area remain elusive. In the present work, we studied the role of Neuregulin (NRG) in the formation and maintenance of the radial glial scaffold in the hippocampal DG of postnatal rats using slice culture. We found that ErbB4 receptors were expressed in vimentin-positive RGCs in DG of postnatal day 6 (P6) rats. Treatment with NRG and Ab-3, the inhibitor of ErbB4, revealed that in P6 rats exogenous NRG promoted the proliferation of Vimentin-positive RGCs in DG. On the other hand, endogenous NRG was found necessary for maintaining the characteristic morphological and immunohistochemical features of these cells. These results indicated that NRG plays a critical role in the formation and maintenance of the radial glial scaffold in the hippocampal DG of postnatal rats. J. Cell. Physiol. (c) 2006 Wiley-Liss, Inc.}, Author = {Zheng, and Feng,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0021-9541}, Journal = {J Cell Physiol}, Keywords = {10 Development;10 Hippocampus;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {0050222}, Organization = {Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.}, Pubmed = {16456862}, Title = {Neuregulin regulates the formation of radial glial scaffold in hippocampal dentate gyrus of postnatal rats}, Uuid = {A03D5AFB-8E5E-45CF-B4F8-5170AF77469B}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jcp.20591}} @article{Zhong:1996, Abstract = {During Drosophila neurogenesis, differential segregation of Numb is necessary for daughter cells of asymmetric divisions to adopt distinct fates, at least partly by biasing the Notch-mediated cell-cell interaction. We have isolated a highly conserved mammalian homolog of Drosophila numb, m-numb. During mouse cortical neurogenesis, m-Numb is asymmetrically localized to the apical membrane of dividing ventricular neural progenitors. Depending upon the orientation of the cleavage plane, m-Numb may be distributed into one or both of the daughter cells. When expressed in Drosophila embryos, m-Numb is localized asymmetrically in dividing neural precursors and rescues the numb mutant phenotype. Furthermore, m-Numb can physically interact with mouse Notch1. We propose that some shared molecular mechanisms, both cell-intrinsic and cell-extrinsic, generate asymmetric cell divisions during neurogenesis of vertebrates and invertebrates. 0896-6273 Journal Article}, Author = {Zhong, W. and Feder, J. N. and Jiang, M. M. and Jan, L. Y. and Jan, Y. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Neuron}, Keywords = {10 Development;Tissue Distribution;Animals;Sequence Homology, Amino Acid;Rats;Mice/*embryology;*Embryo and Fetal Development;Mutation;Membrane Proteins/metabolism;Support, Non-U.S. Gov't;Embryo/metabolism;Cell Membrane/metabolism;Support, U.S. Gov't, P.H.S.;Juvenile Hormones/genetics/*metabolism;Drosophila;Cell Division;Amino Acid Sequence;Molecular Sequence Data;Neurons/metabolism;Receptors, Cell Surface/metabolism;Cerebral Cortex/cytology/*embryology/*metabolism;F}, Number = {1}, Organization = {Howard Hughes Medical Institute, University of California, San Francisco 94143-0724, USA.}, Pages = {43-53}, Pubmed = {8755477}, Title = {Asymmetric localization of a mammalian numb homolog during mouse cortical neurogenesis}, Uuid = {939273D9-778E-4996-8F1F-EAD6CA7D8600}, Volume = {17}, Year = {1996}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8755477}} @article{Zhong:2003, Abstract = {A key question in developmental neurobiology is how the diversity of cell types that make up the mature nervous system are generated from a common set of progenitor cells. Drosophila genes governing temporal cell fate determination and asymmetric cell divisions involving numb may represent evolutionarily conserved mechanisms for regulating cell fate diversification in the developing nervous system. 0896-6273 Journal Article Review Review, Tutorial}, Author = {Zhong, W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Neuron}, Keywords = {Juvenile Hormones/genetics/metabolism;Cell Differentiation/*physiology;10 Development;Cell Lineage/*physiology;Human;Neurons/*cytology/physiology;Stem Cells/*cytology/physiology;Nervous System/cytology/*embryology;Nerve Tissue Proteins/genetics/metabolism;F;Cell Division/*physiology;Animals;Drosophila melanogaster/cytology/embryology/physiology}, Number = {1}, Organization = {Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06511, USA. weimin.zhong\@yale.edu}, Pages = {11-4}, Pubmed = {12526768}, Title = {Diversifying neural cells through order of birth and asymmetry of division}, Uuid = {AD3DDDB1-3EAF-4790-9F71-0167B7A99133}, Volume = {37}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12526768}} @article{Zhou:2002, Abstract = {OLIG1 and OLIG2 are basic-helix-loop-helix (bHLH) transcription factors expressed in the pMN domain of the spinal cord, which sequentially generates motoneurons and oligodendrocytes. In Olig1/2 double-mutant mice, motoneurons are largely eliminated, and oligodendrocyte differentiation is abolished. Lineage tracing data suggest that Olig1(-/-)2(-/-) pMN progenitors instead generate V2 interneurons and then astrocytes. This apparent conversion likely reflects independent roles for OLIG1/2 in specifying motoneuron and oligodendrocyte fates. Olig genes therefore couple neuronal and glial subtype specification, unlike proneural bHLH factors that control the neuron versus glia decision. Our results suggest that in the spinal cord, Olig and proneural genes comprise a combinatorial code for the specification of neurons, astrocytes, and oligodendrocytes, the three fundamental cell types of the central nervous system. 0092-8674 Journal Article}, Author = {Zhou, Q. and Anderson, D. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Cell}, Keywords = {Nerve Tissue Proteins/*deficiency/genetics/metabolism;Neuroglia/cytology/*metabolism;Transcription Factors/deficiency/genetics/metabolism;Animals;Helix-Loop-Helix Motifs/genetics;Neurons/cytology/*metabolism;Female;Cell Lineage/*physiology;Interneurons/cytology/metabolism;G abstr;11 Glia;Male;Oligodendroglia/cytology/metabolism;Cell Differentiation/*physiology;Stem Cells/cytology/*metabolism;Astrocytes/cytology/metabolism;Rhombencephalon/cytology/embryology/metabolism;Mutation/physiology;Homeodomain Proteins/genetics/metabolism;Spinal Cord/cytology/*embryology/metabolism;Mice, Knockout;Support, U.S. Gov't, P.H.S.;Motor Neurons/cytology/metabolism;Mice}, Number = {1}, Organization = {Division of Biology 216-76, California Institute of Technology, Pasadena, CA 91125, USA.}, Pages = {61-73}, Pubmed = {11955447}, Title = {The bHLH transcription factors OLIG2 and OLIG1 couple neuronal and glial subtype specification}, Uuid = {11B34EA1-6852-4CE8-802E-665D363038E3}, Volume = {109}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11955447}} @article{Zhou:2004, Abstract = {Mice with mutations in the Wnt coreceptor low-density lipoprotein receptor-related protein-6 (LRP6) have a smaller and severely disorganized dorsal thalamus and lack thalamocortical projections. Using molecular markers, we showed that most dorsal thalamic and epithalamic neurons were missing, and most of the major dorsal thalamic nuclei were not identifiable. However, the ventral thalamus was essentially unaffected, although the dorsal thalamic defect leads to rostral displacement of portions of the ventral thalamus. Analysis of younger embryos showed that epithalamic and dorsal thalamic neurons were not produced at early stages of development, whereas ventral thalamic neurons were still produced. These defects were accompanied by improper formation of the boundary between dorsal and ventral thalamus, the zona limitans interthalamica (ZLI). Furthermore, the expression of an early marker of posterior forebrain development that marks the compartment from the midbrain-hindbrain junction to the ZLI (including the future dorsal thalamus, pretectum, and midbrain) was disrupted, supporting the idea that diencephalic development is abnormal from very early in embryogenesis. This study provides compelling in vivo evidence that thalamic development requires normal activity of the LRP6-mediated canonical Wnt signaling pathway.}, Author = {Zhou, Cheng-Ji J. and Pinson, Kathleen I. and Pleasure, Samuel J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Cytoskeletal Proteins;10 Development;Signal Transduction;Animals;10 Hippocampus;Trans-Activators;Thalamic Nuclei;Diencephalon;Receptors, LDL;Wnt Proteins;LDL-Receptor Related Proteins;Research Support, U.S. Gov't, P.H.S.;Thalamus;Intercellular Signaling Peptides and Proteins;Mice, Knockout;Morphogenesis;Mice;Proto-Oncogene Proteins;beta Catenin;Gestational Age;Research Support, Non-U.S. Gov't}, Month = {9}, Nlm_Id = {8102140}, Number = {35}, Organization = {Department of Neurology, Program in Neuroscience, University of California, San Francisco 94143-0435, USA.}, Pages = {7632-9}, Pii = {24/35/7632}, Pubmed = {15342729}, Title = {Severe defects in dorsal thalamic development in low-density lipoprotein receptor-related protein-6 mutants}, Uuid = {659D0E96-FD90-4552-94ED-516D3D9A8375}, Volume = {24}, Year = {2004}, url = {papers/Zhou_JNeurosci2004a.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.2123-04.2004}} @article{Zhou:2004a, Abstract = {LRP6 mutant mice have generalized defects in the Wnt/beta-catenin signaling pathway because of the crucial function of LRP6 as a Wnt signaling co-receptor (Pinson et al., 2000). We examined the hippocampal phenotype of single LRP6 mutant mice as well as LRP6/Lef1 double mutant mice. LRP6 mutants had reduced production of dentate granule neurons and abnormalities of the radial glial scaffolding in the forming dentate gyrus. These defects were more severe with the addition of a single Lef1 null allele to an LRP6 null background. Pyramidal cell fields were unaffected in the LRP6, Lef1, or double mutants. The dentate defects were accompanied by decreased numbers of mitotic precursors in the migratory pathway to the dentate and in the displaced proliferative zone in the dentate itself. At earlier gestational ages, there was a reduction in the number of dentate granule cell progenitors in the dentate ventricular zone before the emigration of the earliest differentiated granule neurons and precursors to form the dentate anlage.}, Author = {Zhou, Cheng-Ji J. and Zhao, Chunjie and Pleasure, Samuel J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {10 Development;Signal Transduction;Animals;Transcription Factors;DNA-Binding Proteins;10 Hippocampus;Receptors, LDL;Phenotype;Wnt Proteins;Research Support, U.S. Gov't, P.H.S.;Alleles;Mice, Knockout;Neurons;Lymphoid Enhancer-Binding Factor 1;Neuroglia;Dentate Gyrus;Zebrafish Proteins;Mice;Proto-Oncogene Proteins;Stem Cells;Research Support, Non-U.S. Gov't}, Month = {1}, Nlm_Id = {8102140}, Number = {1}, Organization = {Department of Neurology, Programs in Neuroscience and Developmental Biology, University of California, San Francisco, California 94143-0435, USA.}, Pages = {121-6}, Pii = {24/1/121}, Pubmed = {14715945}, Title = {Wnt signaling mutants have decreased dentate granule cell production and radial glial scaffolding abnormalities}, Uuid = {E0841C8C-7113-11DA-9A4D-000D9346EC2A}, Volume = {24}, Year = {2004}, url = {papers/Zhou_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.4071-03.2004}} @article{Zhou:1999, Abstract = {Chicken ovalbumin upstream promotor-transcription factor I (COUP-TFI), an orphan member of the nuclear receptor superfamily, is highly expressed in the developing nervous systems. In the cerebral cortex of Coup-tfl mutants, cortical layer IV was absent due to excessive cell death, a consequence of the failure of thalamocortical projections. Moreover, subplate neurons underwent improper differentiation and premature cell death during corticogenesis. Our results indicate that the subplate neuron defects lead to the failure of guidance and innervation of thalamocortical projections. Thus, our findings demonstrate a critical role of the subplate in early corticothalamic connectivity and confirm the importance of afferent innervation for the survival of layer IV neurons. These results also substantiate COUP-TFI as an important regulator of neuronal development and differentiation.}, Author = {Zhou, C. and Qiu, Y. and Pereira, F. A. and Crair, M. C. and Tsai, S. Y. and Tsai, M. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Fluorescent Dyes;Cell Differentiation;Animals;Transcription Factors;DNA-Binding Proteins;Neural Pathways;Axons;Mutation;research support, non-u.s. gov't;Antimetabolites;Male;In Situ Hybridization;COUP Transcription Factor I;Thalamus;Cerebral Cortex;Neurons;research support, u.s. gov't, p.h.s.;Carbocyanines;Mice;24 Pubmed search results 2008;Immunohistochemistry;Bromodeoxyuridine;Cell Death;Receptors, Glucocorticoid}, Month = {12}, Nlm_Id = {8809320}, Number = {4}, Organization = {Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.}, Pages = {847-59}, Pii = {S0896-6273(00)81032-6}, Pubmed = {10624948}, Title = {The nuclear orphan receptor COUP-TFI is required for differentiation of subplate neurons and guidance of thalamocortical axons}, Uuid = {A985017D-B453-44FD-9331-5E20029DBB1B}, Volume = {24}, Year = {1999}} @article{Zhou:2006, Abstract = {Mutations or duplications in MECP2 cause Rett and Rett-like syndromes, neurodevelopmental disorders characterized by mental retardation, motor dysfunction, and autistic behaviors. MeCP2 is expressed in many mammalian tissues and functions as a global repressor of transcription; however, the molecular mechanisms by which MeCP2 dysfunction leads to the neural-specific phenotypes of RTT remain poorly understood. Here, we show that neuronal activity and subsequent calcium influx trigger the de novo phosphorylation of MeCP2 at serine 421 (S421) by a CaMKII-dependent mechanism. MeCP2 S421 phosphorylation is induced selectively in the brain in response to physiological stimuli. Significantly, we find that S421 phosphorylation controls the ability of MeCP2 to regulate dendritic patterning, spine morphogenesis, and the activity-dependent induction of Bdnf transcription. These findings suggest that, by triggering MeCP2 phosphorylation, neuronal activity regulates a program of gene expression that mediates nervous system maturation and that disruption of this process in individuals with mutations in MeCP2 may underlie the neural-specific pathology of RTT.}, Author = {Zhou, Zhaolan and Hong, Elizabeth J. and Cohen, Sonia and Zhao, Wen-Ning N. and Ho, Hsin-Yi Henry Y. and Schmidt, Lauren and Chen, Wen G. and Lin, Yingxi and Savner, Erin and Griffith, Eric C. and Hu, Linda and Steen, Judith A. J. and Weitz, Charles J. and Greenberg, Michael E.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0896-6273}, Journal = {Neuron}, Keywords = {Cell Differentiation;Calcium Signaling;Animals;Gene Expression Regulation, Developmental;Serine;Rats;Neuronal Plasticity;Neural Pathways;Brain-Derived Neurotrophic Factor;Methyl-CpG-Binding Protein 2;Dendritic Spines;Phosphorylation;Brain;Synaptic Transmission;Organ Culture Techniques;Ca(2+)-Calmodulin Dependent Protein Kinase;research support, non-u.s. gov't;21 Neurophysiology;Organ Specificity;research support, n.i.h., extramural;24 Pubmed search results 2008;Rett Syndrome}, Month = {10}, Nlm_Id = {8809320}, Number = {2}, Organization = {Neurobiology Program, Children's Hospital Boston, Harvard Medical School, Boston, Massachusetts 02115, USA.}, Pages = {255-69}, Pii = {S0896-6273(06)00775-6}, Pubmed = {17046689}, Title = {Brain-specific phosphorylation of MeCP2 regulates activity-dependent Bdnf transcription, dendritic growth, and spine maturation}, Uuid = {0F6E9701-2FDF-44F9-BF5E-80B4DA816EF2}, Volume = {52}, Year = {2006}, url = {papers/Zhou_Neuron2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuron.2006.09.037}} @article{Zhou:2006a, Abstract = {To better understand the function of the Wnt pathway in the developing telencephalon, we analyzed neocortical development in low density lipoprotein receptor-related protein (LRP) 6 mutants. LRP6 mutant mice are hypomorphic for the canonical Wnt signaling pathway and have hypoplasia of the developing neocortex. While early telencephalic morphogenesis is largely intact in these mice, probably due to compensation by LRP5, the mutant mice develop a dramatically thinner cortical plate. There is a prominent reduction of neurogenesis leading to a thin cortical plate. Reduced proliferation late in gestation probably also contributes to the hypoplasia. Although there are marked decreases in the numbers of layer 6 and layers 2-4 neurons all laminar identities are generated and there is no evidence of compensatory increases in layer 5 neurons. In addition, LRP6 mutants have partial penetrance of a complex of cortical dysmorphologies resembling those found in patients with developmental forms of epilepsy and mental retardation. These include ventricular and marginal zone heterotopias and cobblestone lissencephaly. This analysis demonstrates that canonical Wnt signaling is required for a diverse array of developmental processes in the neocortex in addition to the previously known roles in regulating precursor proliferation and patterning.}, Author = {Zhou, and Borello, and Rubenstein, and Pleasure,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {0306-4522}, Journal = {Neuroscience}, Keywords = {24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7605074}, Organization = {UCSF Mission Bay, Box 2722, Rock Hall, Department of Neurology, 1550 Fourth Street, Room RH-348D, San Francisco, CA 94143-2722, USA; Department of Psychiatry, Programs in Neuroscience and Developmental Biology, University of California, San Francisco, CA, USA.}, Pii = {S0306-4522(06)00932-8}, Pubmed = {16920270}, Title = {Neuronal production and precursor proliferation defects in the neocortex of mice with loss of function in the canonical Wnt signaling pathway}, Uuid = {51F17DD5-2712-4910-99F2-ECAA2F563EDB}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1016/j.neuroscience.2006.07.007}} @article{Zhou:2008, Abstract = {Development of axonal tracts requires interactions between growth cones and the environment. Tracts such as the anterior commissure and internal capsule are defective in mice with null mutation of Celsr3. We generated a conditional Celsr3 allele, allowing regional inactivation. Inactivation in telencephalon, ventral forebrain, or cortex demonstrated essential roles for Celsr3 in neurons that project axons to the anterior commissure and subcerebral targets, as well as in cells that guide axons through the internal capsule. When Celsr3 was inactivated in cortex, subcerebral projections failed to grow, yet corticothalamic axons developed normally, indicating that besides guidepost cells, additional Celsr3-independent cues can assist their progression. These observations provide in vivo evidence that Celsr3-mediated interactions between axons and guidepost cells govern axonal tract formation in mammals.}, Author = {Zhou, Libing and Bar, Isabelle and Achouri, Youn\`{e}s and Campbell, Kenneth and De Backer, Olivier and Hebert, Jean M. and Jones, Kevin and Kessaris, Nicoletta and de Rouvroit, Catherine Lambert and O'Leary, Dennis and Richardson, William D. and Goffinet, Andre M. and Tissir, Fadel}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:35 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Animals;Tissue Culture Techniques;Neural Pathways;Receptors, Cell Surface;Female;Axons;Internal Capsule;research support, non-u.s. gov't;Male;Septal Nuclei;Prosencephalon;Thalamus;Cadherins;Cerebral Cortex;Neurons;Gene Silencing;Mice;24 Pubmed search results 2008}, Month = {5}, Nlm_Id = {0404511}, Number = {5878}, Organization = {Developmental Neurobiology, Universit{\'e} Catholique de Louvain, 1200 Bruxelles, Belgique.}, Pages = {946-9}, Pii = {320/5878/946}, Pubmed = {18487195}, Title = {Early forebrain wiring: genetic dissection using conditional Celsr3 mutant mice}, Uuid = {589EEDB0-B994-4D29-83DC-41AC51125087}, Volume = {320}, Year = {2008}, url = {papers/Zhou_Science2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1155244}} @article{Zhu:1999, Abstract = {0002-9440 Journal Article Review Review, Tutorial}, Author = {Zhu, X. and Raina, A. K. and Smith, M. A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Am J Pathol}, Keywords = {Mice, Neurologic Mutants/*genetics;Mutation;*Cell Cycle;Cell Differentiation;Neurodegenerative Diseases/*pathology;Cerebellum/pathology;EE pdf;Neurons/pathology/*physiology;08 Aberrant cell cycle;Cell Death;Animals;Disease Models, Animal;Mice;*Cell Division;Potassium Channels/genetics}, Number = {2}, Organization = {Institute of Pathology, Case Western Reserve University, Cleveland, Ohio, USA.}, Pages = {327-9}, Pubmed = {10433924}, Title = {Cell cycle events in neurons. Proliferation or death?}, Uuid = {590B7AA2-D037-4A94-A082-56521B4E55B6}, Volume = {155}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10433924}} @article{Zhu:2003, Abstract = {Proliferating cells are hardly detectable in the adult mammalian brain by microscopy of stained sections, but after pre-labeling with radioactive thymidine or 5'-bromo-2-deoxyuridine (BrdU), either marks the nucleus, as do mitosis-related proteins such as Ki67 and PCNA. Engineered virus may also be used to mark proliferating cells. One alternative approach is to use the enzyme ribonucleotide reductase (RNR), expressed by proliferating cells, but not by quiescent ones. A monoclonal antibody against the M1 subunit of RNR was used to visualize proliferating cells in the brains of adult normal rats, rabbits, pigs and sheep. Stem cells were distinctly outlined. In the subgranular layer in the hippocampal dentate gyrus, most RNR immunoreactive cells were bipolar to multipolar, and had a large cell body and long processes. Two different populations of RNR expressing cells were visualized in the subventricular zone in the forebrain, one dominated by small, bipolar cells extending into the rostral migratory stream, while the other was formed by large multipolar cells, adjacent to the ependyma, with processes extending to the lateral ventricle. Furthermore, rare RNR-expressing cells were recognized throughout the brain. The RNR immunoreactive cells were immature, as they did not express any marker characterizing differentiated neurons and glial cells, except for a fraction that co-expressed the gliofibrillary acidic protein. BrdU and RNR were co-localized in proliferating cells in animals pretreated with BrdU. We conclude that RNR immunohistochemistry can accurately visualize proliferating cells, including stem cells, in adult mammalian brains. The occurrence of processes at cell proliferation is elucidated. Further, the advocated approach does not require any pre-labeling, and can be carried out on fixed tissues.}, Author = {Zhu, Hong and Wang, Zhan-You Y. and Hansson, Hans-Arne A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0006-8993}, Journal = {Brain Res}, Keywords = {Rabbits;Protein Subunits;Animals;Rats;Microscopy, Confocal;Radiation-Sensitizing Agents;Comparative Study;Brain;Female;Sheep;Swine;23 Technique;Species Specificity;Calcium-Binding Protein, Vitamin D-Dependent;Neurofilament Proteins;Male;01 Adult neurogenesis general;Ribonucleotide Reductases;Support, Non-U.S. Gov't;Cell Division;Immunohistochemistry;Bromodeoxyuridine;Stem Cells;Biological Markers;Glial Fibrillary Acidic Protein}, Medline = {22718792}, Month = {7}, Nlm_Id = {0045503}, Number = {2}, Organization = {Institute of Anatomy and Cell Biology, G{\"o}teborg University, P.O. Box 420, SE 40530 Gothenburg, Sweden.}, Pages = {180-9}, Pii = {S0006899303026271}, Pubmed = {12834878}, Title = {Visualization of proliferating cells in the adult mammalian brain with the aid of ribonucleotide reductase}, Uuid = {7D277A51-B07E-4755-9E6D-A3016CD005C2}, Volume = {977}, Year = {2003}, url = {papers/Zhu_BrainRes2003.pdf}} @article{Zhu:2005, Abstract = {Neural stem cells (NSCs) are present not only in the developing nervous systems, but also in the adult human central nervous system (CNS). It is long thought that the subventricular zone of the lateral ventricles and the dentate gyrus of the hippocampus are the main sources of human adult NSCs, which are considered to be a reservoir of new neural cells. Recently adult NSCs with potential neural capacity have been isolated from white matter and inferior prefrontal subcortex in the human brain. Rapid advances in the stem cell biology have raised appealing possibilities of replacing damaged or lost neural cells by transplantation of in vitro-expanded stem cells and/or their neuronal progeny. However, sources of stem cells, large scale expansion, control of the differentiations, and tracking in vivo represent formidable challenges. In this paper we review the characteristics of the adult human NSCs, their potentiality in terms of proliferation and differentiation capabilities, as well as their large scale expansion for clinical needs. This review focuses on the major advances in brain stem cell-based therapy from the clinical perspective, and summarizes our work in clinical phase I-II trials with autologuous transplantation of adult NSCs for patients with open brain trauma. It also describes multiple approaches to monitor adult human NSCs labeled superparamagnetic nanoparticles after transplantation and explores the intriguing possibility of stem cell transplantation.}, Author = {Zhu, J. and Wu, X. and Zhang, H. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:46 -0400}, Issn = {1389-4501}, Journal = {Curr Drug Targets}, Keywords = {delete_this;24 Pubmed search results 2008}, Month = {2}, Nlm_Id = {100960531}, Number = {1}, Organization = {Department of Neurosurgery, Fudan University Huashan Hospital, 12 Wulumuqi Zhong Road, Shanghai, 200040, China. jzhu\@fudan.edu.cn.}, Pages = {97-110}, Pubmed = {15720217}, Title = {Adult neural stem cell therapy: expansion in vitro, tracking in vivo and clinical transplantation}, Uuid = {4F721768-1537-46C7-A1A8-0F146BB9633C}, Volume = {6}, Year = {2005}} @article{Zhu:2000a, Abstract = {Cortical dysplasia has a strong association with epilepsy in humans, but the underlying mechanisms for this are poorly understood. In utero irradiation of rats produces diffuse cortical dysplasia and neuronal heterotopia in the neocortex and hippocampus. Using in vitro neocortical slices, whole-cell patch-clamp recordings were obtained from pyramidal neurons in dysplastic cortex and control neocortex. Spontaneous IPSCs were reduced in amplitude (35\%) and frequency (70\%) in pyramidal cells from dysplastic cortex. Miniature IPSCs were reduced in frequency (66\%) in dysplastic cortex. Two additional measures of cortical inhibition, monosynaptic evoked IPSCs and paired pulse depression of evoked EPSCs, were also impaired in dysplastic cortex. Spontaneous EPSCs were increased in amplitude (42\%) and frequency (77\%) in dysplastic cortex, but miniature EPSCs were not different between the two groups. These data demonstrate significant physiological impairment in inhibitory synaptic transmission in experimental cortical dysplasia. This supports previous immunohistochemical findings in this model and observations in humans of a reduction in the density of inhibitory interneurons in dysplastic cortex.}, Author = {Zhu, W. J. and Roper, S. N.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:46:00 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Gamma Rays;Excitatory Amino Acid Antagonists;10 Development;Electric Stimulation;Animals;Evoked Potentials;Excitatory Postsynaptic Potentials;Rats;Pregnancy;Synaptic Transmission;Neocortex;Female;Cell Membrane;Rats, Sprague-Dawley;Patch-Clamp Techniques;Pyramidal Cells;Tetrodotoxin;Disease Models, Animal;Receptors, GABA-A;Maternal Exposure;10 genetics malformation;research support, u.s. gov't, p.h.s.;24 Pubmed search results 2008;Choristoma;Neural Inhibition;Abnormalities, Radiation-Induced;in vitro}, Month = {12}, Nlm_Id = {8102140}, Number = {23}, Organization = {Department of Neurological Surgery, University of Florida, and Malcolm Randall Veterans Administration Medical Center, Gainesville, Florida 32610-0265, USA.}, Pages = {8925-31}, Pii = {20/23/8925}, Pubmed = {11102503}, Title = {Reduced inhibition in an animal model of cortical dysplasia}, Uuid = {C1965388-3255-4B25-9F85-E2FB49F82D92}, Volume = {20}, Year = {2000}, url = {papers/Zhu_JNeurosci2000.pdf}} @article{Zhu:2000, Abstract = {Changes in the arborization and electrical excitability of the apical dendritic tufts of pyramidal cells of cortical layer 5 were examined during the first 2 months (postnatal days (P)2-56) of postnatal development in rats. Reconstructions of biocytin-filled neurons showed that the apical dendritic trunk was continually growing, becoming longer and thicker and that the distance between the tuft and soma increased more than 5-fold. In P2 animals, both the tuft and soma had a high input resistance (>500 MOmega) and the tuft was electrotonically close to the soma. In contrast, the apical tuft and soma of P56 neurons had a low input resistance (<50 MOmega) and they were electrotonically isolated from each other. Depolarizing current pulses injected into the tuft of P2 cells generated mostly Na+-dependent regenerative dendritic potentials of short duration ( approximately 15 ms) while in the tuft of P56 animals, complex regenerative potentials were generated which had a longer duration ( approximately 55 ms) and were Na+ and Ca2+ dependent. In young and juvenile animals (P14-28) dendritic regenerative potentials could be restricted to the apical dendritic tuft whereas in adult animals (>P42), the complex regenerative potentials frequently occurred simultaneously with somatic action potentials. The main developmental change in layer 5 pyramidal neurons, as assayed with square pulse current injections and synaptic stimulations, is the progressive electrotonic isolation of the dendritic tuft from the soma. This change is concomitant with the appearance of complex, mostly Na+- and Ca2+-dependent, regenerative dendritic potentials initiated partly in the tuft and partly in the axon. The coupling of the dendritic tuft and axonal initiation zones for regenerative potentials by active dendritic Na+ and Ca2+ conductances enables mature layer 5 pyramidal neurons to detect selectively the salient distal synaptic inputs and coincident synaptic inputs arriving at different cortical layers.}, Author = {Zhu, J. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 12:12:02 -0400}, Issn = {0022-3751}, Journal = {J Physiol}, Keywords = {Cell Differentiation;Electric Stimulation;Animals;In Vitro;Aging;Rats;Neocortex;Nickel;Cell Membrane;Pyramidal Cells;Calcium;Tetrodotoxin;Rats, Wistar;Dendrites;Support, Non-U.S. Gov't;Action Potentials;Cadmium;18 Classic Neuroanatomy Physiology;Excitatory Postsynaptic Potentials}, Medline = {20381219}, Month = {8}, Nlm_Id = {0266262}, Organization = {Abteilung Zellphysiologie, Max-Planck-Institut fur medizinische Forschung, Jahnstrasse 29, D-69120 Heidelberg, Germany. zhuju\@cshl.org}, Pages = {571-87}, Pii = {PHY_0791}, Pubmed = {10922009}, Title = {Maturation of layer 5 neocortical pyramidal neurons: amplifying salient layer 1 and layer 4 inputs by Ca2+ action potentials in adult rat tuft dendrites}, Uuid = {1C9D4F12-94B3-4031-976C-ABBA0909CEF1}, Volume = {526 Pt 3}, Year = {2000}, url = {papers/Zhu_JPhysiol2000.pdf}} @article{Zhu:1999a, Abstract = {Formation of the normal mammalian cerebral cortex requires the migration of GABAergic inhibitory interneurons from an extracortical origin, the lateral ganglionic eminence (LGE). Mechanisms guiding the migratory direction of these neurons, or other neurons in the neocortex, are not well understood. We have used an explant assay to study GABAergic neuronal migration and found that the ventricular zone (VZ) of the LGE is repulsive to GABAergic neurons. Furthermore, the secreted protein Slit is a chemorepellent guiding the migratory direction of GABAergic neurons, and blockade of endogenous Slit signaling inhibits the repulsive activity in the VZ. These results have revealed a cellular source of guidance for GABAergic neurons, demonstrated a molecular cue important for cortical development, and suggested a guidance mechanism for the migration of extracortical neurons into the neocortex.}, Author = {Zhu, Y. and Li, H. and Zhou, L. and Wu, J. Y. and Rao, Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Neuron}, Keywords = {Fetus/cytology;Rats, Sprague-Dawley;Rats;Corpus Striatum/*cytology/embryology;Neurons/chemistry/*cytology;Cell Communication/physiology;Animal;Neocortex/*cytology/embryology;Organ Culture;Cell Movement/*physiology;Support, Non-U.S. Gov't;12 Interneuron development;GABA/*physiology;H}, Number = {3}, Organization = {Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.}, Pages = {473-85.}, Title = {Cellular and molecular guidance of GABAergic neuronal migration from an extracortical origin to the neocortex}, Uuid = {D9D42D89-8A34-4A8C-9724-92556AF33CAF}, Volume = {23}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10433260}} @article{Ziegelhoeffer:2004, Abstract = {Bone marrow-Derived cells have been proposed to form new vessels or at least incorporate into growing vessels in adult organisms under certain physiological and pathological conditions. We investigated whether bone marrow-Derived cells incorporate into vessels using mouse models of hindlimb ischemia (arteriogenesis and angiogenesis) and tumor growth. C57BL/6 wild-type mice were lethally irradiated and transplanted with bone marrow cells from littermates expressing enhanced green fluorescent protein (GFP). At least 6 weeks after bone marrow transplantation, the animals underwent unilateral femoral artery occlusions with or without pretreatment with vascular endothelial growth factor or were subcutaneously implanted with methylcholanthrene-induced fibrosarcoma (BFS-1) cells. Seven and 21 days after surgery, proximal hindlimb muscles with growing collateral arteries and ischemic gastrocnemius muscles as well as grown tumors and various organs were excised for histological analysis. We failed to colocalize GFP signals with endothelial or smooth muscle cell markers. Occasionally, the use of high-power laser scanning confocal microscopy uncovered false-positive results because of overlap of different fluorescent signals from adjacent cells. Nevertheless, we observed accumulations of GFP-positive cells around growing collateral arteries (3-fold increase versus nonoccluded side, P<0.001) and in ischemic distal hindlimbs. These cells were identified as fibroblasts, pericytes, and primarily leukocytes that stained positive for several growth factors and chemokines. Our findings suggest that in the adult organism, bone marrow-Derived cells do not promote vascular growth by incorporating into vessel walls but may function as supporting cells.}, Author = {Ziegelhoeffer, Tibor and Fernandez, Borja and Kostin, Sawa and Heil, Matthias and Voswinckel, Robert and Helisch, Armin and Schaper, Wolfgang}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1524-4571}, Journal = {Circ Res}, Keywords = {Ischemia;Research Support, Non-U.S. Gov't;Cell Differentiation;Animals;Blood Vessels;Fibrosarcoma;Pericytes;Microscopy, Confocal;Ligation;Neoplasm Transplantation;Fibroblasts;Mice, Transgenic;Mice, Inbred C57BL;11 Glia;Green Fluorescent Proteins;Neovascularization, Physiologic;Radiation Chimera;Femoral Artery;Neovascularization, Pathologic;Bone Marrow Cells;Leukocytes;Organ Specificity;Hindlimb;Mice;Muscle, Smooth, Vascular;Genes, Reporter;Luminescent Proteins;Endothelium, Vascular}, Month = {2}, Nlm_Id = {0047103}, Number = {2}, Organization = {Max-Planck-Institute for Clinical &Physiological Research, Bad Nauheim, Germany. t.ziegelhoeffer\@kerckhoff.mpg.de}, Pages = {230-8}, Pii = {01.RES.0000110419.50982.1C}, Pubmed = {14656934}, Title = {Bone marrow-derived cells do not incorporate into the adult growing vasculature}, Uuid = {0BE91453-FBD2-4D41-8E4B-2F2D5AF921EF}, Volume = {94}, Year = {2004}, Bdsk-Url-1 = {http://dx.doi.org/10.1161/01.RES.0000110419.50982.1C}} @article{Zietlow:1999, Abstract = {When embryonic dopaminergic neurons are transplanted into the adult brain, approximately 95\%die within a few days. To assess whether microglia activated during transplantation might be responsible for this rapid death, we examined the effect of microglia on rat embryonic dopaminergic neurons in vitro. Conditioned medium from 7-day-old microglia was found to decrease the number of dopamine neurons surviving in primary culture, but activation of the microglia with N-formyl-methionyl-leucyl-phenylalanine (FMLP) or Zymosan A did not increase the toxicity of the conditioned medium. We next tested the effect of coculturing microglia and dopaminergic neurons by placing microglia in semipermeable well inserts over the neuronal cultures. The presence of microglia now increased dopaminergic neuronal survival, microglial activation again having no effect. To increase yet further the possible interactions between microglia and neurons, the mesencephalic cells and microglia were mixed together and placed as a tissue in three-dimensional culture, and here again the presence of microglia increased dopaminergic neuronal survival with no effect of activation. Contact of microglia with the mesencephalic cells therefore converted them from being toxic to dopaminergic neurons to promoting their survival. The change in microglial effect from toxic to protective was caused by soluble molecules secreted by cells in the neuronal cultures, as conditioned medium derived from microglia-neuronal cocultures also had a dopaminergic neuron survival effect, indicating that microglia in cocultures behave differently from microglia removed from neuronal and glial influence. Microglia cocultured with either neurons or astrocytes downregulated inducible nitric oxide synthase (iNOS), indicating a decrease in the production of nitric oxide and possibly other toxic molecules. These findings indicate that in their natural environment, microglia are likely to be beneficial for the survival of embryonic dopaminergic grafts.}, Author = {Zietlow, R. and Dunnett, S. B. and Fawcett, J. W.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Cell Survival;Pregnancy;Dopamine;Neurotoxins;Animals;Cells, Cultured;Brain Tissue Transplantation;Rats;Neuroprotective Agents;Female;Cell Communication;Rats, Sprague-Dawley;Culture Media, Conditioned;Microglia;Not relevant;Fetal Tissue Transplantation;11 Glia;Nitric-Oxide Synthase;Substantia Nigra;Support, Non-U.S. Gov't;Cerebral Cortex;Neurons;Zymosan;N-Formylmethionine Leucyl-Phenylalanine;Cell Culture;Graft Survival}, Medline = {99233957}, Month = {5}, Nlm_Id = {8918110}, Number = {5}, Organization = {MRC Cambridge Centre for Brain Repair, University of Cambridge, UK.}, Pages = {1657-67}, Pubmed = {10215919}, Title = {The effect of microglia on embryonic dopaminergic neuronal survival in vitro: diffusible signals from neurons and glia change microglia from neurotoxic to neuroprotective}, Uuid = {2F5111C6-B078-4167-9A19-6D55E3BE3D84}, Volume = {11}, Year = {1999}, url = {papers/Zietlow_EurJNeurosci1999.pdf}} @article{Zigova:1998, Abstract = {We have investigated the suitability of a recently identified and characterized population of neuronal progenitor cells for their potential use in the replacement of degenerating or damaged neurons in the mammalian brain. The unique population of neuronal progenitor cells is situated in a well-delineated region of the anterior part of the neonatal subventricular zone (referred to as SVZa). This region can be separated from the remaining proliferative, gliogenic, subventricular zone encircling the lateral ventricles of the forebrain. Because the neurons arising from the highly enriched neurogenic progenitor cell population of the SVZa ordinarily migrate considerable distances and ultimately express the neurotransmitters GABA and dopamine, we have examined whether they could serve as an alternative source of tissue for neural transplantation. SVZa cells from postnatal day 0-2 rats, prelabeled by intraperitoneal injections of the cell proliferation marker BrdU, were implanted into the striatum of adult rats approximately 1 mo after unilateral denervation by 6-OHDA. To examine the spatio-temporal distribution and phenotype of the transplanted SVZa cells, the experimental recipients were perfused at short (less than 1 wk), intermediate (2-3 wk) and long (5 mo) postimplantation times. The host brains were sectioned and stained with an antibody to BrdU and one of several cell-type specific markers to determine the phenotypic characteristics of the transplanted SVZa cells. To identify neurons we used the neuron-specific antibody TuJ1, or antimembrane-associated protein 2 (MAP-2), and anti-GFAP was used to identify astrocytic glia. At all studied intervals the majority of the surviving SVZa cells exhibited a neuronal phenotype. Moreover, morphologically they could be distinguished from the cells of the host striatum because they resembled the intrinsic granule cells of the olfactory bulb, their usual fate. At longer times, a greater number of the transplanted SVZa cells had migrated from their site of implantation, often towards an outlying blood vessel, and the density of cells within the core of the transplant was reduced. Furthermore, there were rarely signs of transplant rejection or a glial scar surrounding the transplant. In the core of the transplant there were low numbers of GFAP-positive cells, indicating that the transplanted SVZa cells, predominantly TuJ1- positive/MAP2-positive, express a neuronal phenotype. Collectively, the propensity of the SVZa cells to express a neuronal phenotype and to survive and integrate in the striatal environment suggest that they may be useful in the reconstruction of the brain following CNS injury or disease.}, Author = {Zigova, T. and Pencea, V. and Betarbet, R. and Wiegand, S. J. and Alexander, C. and Bakay, R. A. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Issn = {0963-6897}, Journal = {Cell Transplant}, Keywords = {Cell Differentiation;Cerebral Ventricles;L abstr;Cell Survival;24 Pubmed search results 2008;Corpus Striatum;Oxidopamine/toxicity;Interneurons;Bromodeoxyuridine/metabolism;Animals;Cerebral Ventricles/cytology;Research Support, U.S. Gov't, P.H.S.;Cell Movement;Brain Tissue Transplantation;Phenotype;Cell Count;Bromodeoxyuridine;Oxidopamine;Olfactory Bulb;Corpus Striatum/drug effects/*pathology/*transplantation;Neurons/metabolism/*pathology;Brain Tissue Transplantation/*pathology/physiology;Support, U.S. Gov't, P.H.S.;Interneurons/cytology;Animal;Rats, Sprague-Dawley;17 Transplant Regeneration;Rats;Olfactory Bulb/cytology;Animals, Newborn;Stem Cells;Support, Non-U.S. Gov't;Research Support, Non-U.S. Gov't;Neurons;Stem Cells/metabolism/*pathology}, Medline = {98248010}, Nlm_Id = {9208854}, Number = {2}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.}, Pages = {137-56.}, Pii = {S0963689798000098}, Pubmed = {9588596}, Title = {Neuronal progenitor cells of the neonatal subventricular zone differentiate and disperse following transplantation into the adult rat striatum}, Uuid = {2DAEB83A-1C3E-41DB-9120-3BB46337B65F}, Volume = {7}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9588596}} @article{Zigova:1996, Abstract = {The cells arising in the anterior part of the subventricular zone (SVZa) migrate along a well-demarcated pathway which lacks radial glial fibers to the olfactory bulb where they differentiate into interneurons of the granule cell layer or glomerular layer (Luskin, 1993, Neuron 11, 173). To analyze the mechanisms underlying this highly directed migration, we have compared the migratory behavior of unmanipulated SVZa-derived cells to that of homotopically transplanted SVZa cells and of heterotopically transplanted telencephalic ventricular zone (VZ) cells that ordinarily migrate in association with radial glial fibers. To identify the phenotype of the SVZa progenitor cells prior to their transplantation, we characterized them in vitro using cell type-specific markers. After 1 day in culture nearly all the SVZa cells were stained with TuJ1, a neuron-specific marker; only an occasional cell exhibited a glial phenotype as judged by the presence of GFAP-immunoreactivity. This indicates that SVZa cells express a neuronal phenotype. To reveal the spatiotemporal distribution of homotopically transplanted neonatal SVZa cells in a host brain, dissociated SVZa cells from Postnatal Day 0 (P0)-P2 animals were labeled with the lipophilic dye PKH26 or the cell proliferation marker BrdU and implanted into the SVZa of host animals of the same age. Within the first week after transplantation there were vast numbers of labeled cells throughout the pathway. Over the next 2 weeks the labeled cells migrated into the overlying cellular layer of the olfactory bulb and began to differentiate, and within 4 weeks the transplanted cells had reached their final positions in the granule cell and glomerular layers of the olfactory bulb in the same proportions as for unmanipulated SVZa-derived cells. While en route to the olfactory bulb the homotopically transplanted cells never strayed from the migratory pathway. In contrast, heterotopically transplanted VZ cells from the embryonic telencephalon did not undergo migration although they did differentiate. These results demonstrate that the homotopically transplanted SVZa-derived cells adopt a mode of migration indistinguishable from that ordinarily utilized by SVZa-derived neurons and that the VZ cells are unable to decipher the same set of guidance cues.}, Author = {Zigova, T. and Betarbet, R. and Soteres, B. J. and Brock, S. and Bakay, R. A. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0012-1606}, Journal = {Dev Biol}, Keywords = {Research Support, Non-U.S. Gov't;Telencephalon;17 Transplant Regeneration;Cell Transplantation;Rats, Sprague-Dawley;Phenotype;Rats;Research Support, U.S. Gov't, P.H.S.;Stem Cells;Cell Survival;Olfactory Bulb;Animals, Newborn;Transplantation, Heterotopic;Cells, Cultured;Animals;Cell Movement;Neurons}, Medline = {96187867}, Month = {2}, Nlm_Id = {0372762}, Number = {2}, Organization = {Department of Anatomy and Cell Biology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.}, Pages = {459-74}, Pii = {S0012-1606(96)90040-8}, Pubmed = {8606005}, Title = {A comparison of the patterns of migration and the destinations of homotopically transplanted neonatal subventricular zone cells and heterotopically transplanted telencephalic ventricular zone cells}, Uuid = {FBEBFC97-D067-11DA-8A8C-000D9346EC2A}, Volume = {173}, Year = {1996}, Bdsk-Url-1 = {http://dx.doi.org/10.1006/dbio.1996.0040}} @article{Zigova:1998a, Abstract = {We have previously demonstrated that the most rostral part of the subventricular zone (SVZ) is a source of neuronal progenitor cells whose progeny are destined to become interneurons of the olfactory bulb. To determine whether the number of newly generated neurons in the adult olfactory bulb could be increased by the administration of an exogenous factor, brain-derived neurotrophic factor (BDNF) was infused for 12 days into the right lateral ventricle of adult rat brains. The production of new cells was monitored by either the intraventricular infusion or intraperitoneal injection of the cell proliferation marker BrdU. In both experimental paradigms we observed significantly more BrdU-labeled cells in the olfactory bulbs on the BDNF-infused side than in the olfactory bulb of PBS-infused animals. Analysis of the BDNF- infused brains of animals injected intraperitoneally with BrdU demonstrated a 100\%increase in the number of BrdU-labeled cells in the bulb, the preponderance ( approximately 90\%) of which were double- labeled with a neuron-specific antibody. These results demonstrate that the generation and/or survival of new neurons in the adult brain can be increased substantially by an exogenous factor. Furthermore, the SVZ, and in particular the rostral part, may constitute a reserve pool of progenitor cells available for neuronal replacement in the diseased or damaged brain.}, Author = {Zigova, T. and Pencea, V. and Wiegand, S. J. and Luskin, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Journal = {Mol Cell Neurosci}, Keywords = {Olfactory Bulb/cytology/*drug effects;Receptor, Ciliary Neurotrophic Factor;Rats;Stem Cells/cytology/*drug effects;Brain-Derived Neurotrophic Factor/administration &dosage/*pharmacology;Cell Count;Rats, Sprague-Dawley;Animal;Injections, Intraventricular;Bromodeoxyuridine/administration &dosage/pharmacology;Cell Lineage;Receptor Protein-Tyrosine Kinases/biosynthesis/genetics;Support, Non-U.S. Gov't;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Nerve Tissue Proteins/biosynthesis/genetics;C pdf;Injections, Intraperitoneal;Cell Division/drug effects;Receptors, Nerve Growth Factor/biosynthesis/genetics}, Number = {4}, Organization = {Department of Cell Biology, Emory University School of Medicine, Atlanta, Georgia, 30322, USA.}, Pages = {234-45.}, Title = {Intraventricular administration of BDNF increases the number of newly generated neurons in the adult olfactory bulb}, Uuid = {BAAD845B-B595-42D4-A132-A1170B654016}, Volume = {11}, Year = {1998}, url = {papers/Zigova_MolCellNeurosci1998}} @article{Zilles:1998, Abstract = {Epileptiform activity was previously described [Luhmann et al. (1998) Eur. J. Neurosci., 10, 3085-3094] in the neocortex of the adult rat following freeze lesioning of the newborn neocortex. After a survival time of 3 months, a small area of dysplastic cortex surrounded by histologically normal (exofocal) neocortex was observed. The dysplastic cortex is characterized by the formation of a small sulcus and a three- to four-layered architecture. Two questions are addressed here: (i) is the hyperexcitability associated with changes in binding to major excitatory and inhibitory transmitter receptors in the dysplastic cortex?; and (ii) do such changes also occur in the exofocal cortex? Alterations in binding to glutamatergic N-methyl-D-aspartate (NMDA), (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate and GABA(A) and GABA(B) (gamma-aminobutyric acid) receptors are demonstrated with quantitative in vitro receptor autoradiography by using the ligands [3H]MK-801, [3H]AMPA, [3H]kainate, [3H]muscimol and [3H]baclofen, respectively. In the dysplastic cortex, the binding to NMDA, AMPA and kainate receptors is significantly increased, whereas the binding to GABA(A) and GABA(B) receptors is reduced. Exofocal areas of the lesioned hemisphere show an imbalance between excitatory and inhibitory receptor binding with an up-regulation of the binding to AMPA and kainate, and a down-regulation to GABA(A) receptors. The binding to GABA(B) and NMDA receptors is not significantly changed in the exofocal areas. The imbalance between excitatory and inhibitory receptors may cause the hyperexcitability, as previously found in the identical experimental model, and may also induce epileptiform activity in the human cortex with migration disorders.}, Author = {Zilles, K. and Q{\"u}, M. and Schleicher, A. and Luhmann, H. J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:46 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Binding Sites;Animals;Rats;21 Epilepsy;Neocortex;Cell Movement;Rats, Wistar;Models, Anatomic;Receptors, GABA-B;Animals, Newborn;Receptors, GABA-A;Neurons;21 Neurophysiology;Receptors, Kainic Acid;Cryosurgery;24 Pubmed search results 2008;Autoradiography;Models, Neurological}, Medline = {99000143}, Month = {10}, Nlm_Id = {8918110}, Number = {10}, Organization = {C. & O. Vogt Institute of Brain Research, University of D{\"u}sseldorf, Germany. zilles\@hirn.uni-duesseldorf.de}, Pages = {3095-106}, Pubmed = {9786204}, Title = {Characterization of neuronal migration disorders in neocortical structures: quantitative receptor autoradiography of ionotropic glutamate, GABA(A) and GABA(B) receptors}, Uuid = {C50329F6-2159-47CD-A604-B7DFABF949C8}, Volume = {10}, Year = {1998}} @article{Zimmer:2004, Abstract = {Projection neurons destined for the cortical plate are generated sequentially from the proliferative ventricular and subventricular zones (VZ/SVZ) of the pallium. However, the respective contribution of both proliferative zones to the generation of cortical plate neurons is better established in humans and non-human primates than in rodents. We identified Cux2 as a new marker for murine cortical subpopulations and used it to provide new insights to the development of the mouse cortex. Cux2 is an orthologue of the Drosophila cut gene, which encodes a homeodomain protein involved in neuronal specification. During cortical development Cux2 identifies two subpopulations with different spatial origins, migratory behaviours and phenotypic characteristics: (i) a population of interneurons, which invades the pallium from the subpallium; and (ii) a neuronal population produced in the pallium around embryonic day 11.5, which divides in the SVZ and accumulates in the intermediate zone (IZ). Subsequently, Cux2 is a marker of upper cortical layers. Using different molecular markers and Pax6-deficient mice, we provide data that suggest a relationship between the early-determined Cux2-positive neuronal precursors in the SVZ/IZ and upper layer neurons. This suggests that laminar determination of upper cortical layer neurons occurs during the earliest stages of corticogenesis.}, Author = {Zimmer, C{\'e}line and Tiveron, Marie-Catherine C. and Bodmer, Rolf and Cremer, Harold}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1047-3211}, Journal = {Cereb Cortex}, Keywords = {Cerebral Cortex;Neurons;Cell Differentiation;Gene Expression Regulation, Developmental;Mice;Research Support, Non-U.S. Gov't;03 Adult neurogenesis progenitor source;Comparative Study;Mice, Inbred BALB C;Mice, Inbred C57BL;Cell Division;Mice, Mutant Strains;Animals;Cerebral Ventricles;Homeodomain Proteins;Mice, Neurologic Mutants;Cell Lineage}, Month = {12}, Nlm_Id = {9110718}, Number = {12}, Organization = {Developmental Biology Institute of Marseille, NMDA, Campus de Luminy case 907, 13288 Marseille Cedex 9, France.}, Pages = {1408-20}, Pii = {bhh102}, Pubmed = {15238450}, Title = {Dynamics of Cux2 expression suggests that an early pool of SVZ precursors is fated to become upper cortical layer neurons}, Uuid = {AB53D074-C3F4-41EC-8759-78298DC14F1C}, Volume = {14}, Year = {2004}, url = {papers/Zimmer_CerebCortex2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1093/cercor/bhh102}} @article{Zin-Ka-Ieu:1998, Abstract = {Previous observations in intact rats have indicated that axons from the ventrolateral thalamic nucleus (VL) establish direct axo-somatic or axo-dendritic contacts onto frontal cortical neurons projecting to the striatum. The embryonic frontal cortex was grafted into the damaged frontal cortex of newborn rats to study the capacity of homotopic transplants to restore the thalamo-fronto-striate pathway. Several months later, grafted neurons projecting to the striatum were identified by injecting a retrograde neurotracer (subunit b of the cholera toxin) into the ipsilateral caudate putamen. In the same animal, axons and terminations from the VL were labeled within the transplant with an anterograde neurotracer (Phaseolus vulgaris leuco-agglutinin) injected into the ipsilateral VL. The findings show that VL axons establish direct synaptic contacts onto grafted neurons projecting to the striatum. Although the synaptic contacts were scarce in the transplants, their organization was similar to that observed in intact rats. The contacts were axo-somatic or axo-dendritic. Our observations for the first time indicate that synaptic contacts are formed in cortical grafts and that fetal frontal cortex is susceptible to develop appropriate synaptic integration within the host thalamo-fronto-striate system.}, Author = {Zin-Ka-Ieu, S. and Roger, M. and Arnault, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:46 -0400}, Issn = {0168-0102}, Journal = {Neurosci Res}, Keywords = {Cholera Toxin;Animals;Synapses;Corpus Striatum;Brain Tissue Transplantation;Rats;Neural Pathways;Cells, Cultured;Frontal Lobe;Neocortex;Neurons, Afferent;Rats, Wistar;Motor Cortex;Fetal Tissue Transplantation;Animals, Newborn;Thalamus;Neurons;Wheat Germ Agglutinin-Horseradish Peroxidase Conjugate;Somatosensory Cortex;24 Pubmed search results 2008;Microscopy, Electron;Phytohemagglutinins}, Medline = {99025445}, Month = {8}, Nlm_Id = {8500749}, Number = {4}, Organization = {CNRS UMR 6558, D{\'e}partement des Neurosciences, Universit{\'e} de Poitiers, France.}, Pages = {325-36}, Pii = {S0168010298000637}, Pubmed = {9809591}, Title = {Neonatal lesion of the rat's frontal cortex and subsequent transplantation of embryonic frontal cortex: evidence of appropriate synaptic integration of the graft neurons within the host thalamo-fronto-striate circuit}, Uuid = {7C3FD36B-6248-4CC2-9833-5DDA7E73E96A}, Volume = {31}, Year = {1998}} @article{Zin-Ka-Ieu:1999, Abstract = {Previous light microscopical studies have indicated that fibres from the ventrolateral thalamic nucleus (VL) establish direct axo-somatic and axo-dendritic presumed contacts with layers III and V neurones of the intact frontal cortex projecting to the striatum. Additional experiments provided evidence that this thalamo-fronto-striate pathway could be partly reconstructed by transplantation of embryonic frontal tissue into the damaged cortex. The present study was undertaken to validate these results at the ultrastructural level. Several months after the transplantation of fetal frontal tissue into the damaged frontal cortex of newborn rats, a retrograde neurotracer (subunit b of the cholera toxin) was used to label the grafted neurones projecting to the striatum whereas an anterograde neurotracer (Phaseolus vulgaris leuco-agglutinin) was used to label within the transplant, axons and terminations arising from the VL. The same injection procedures were applied to intact adult rats (control). The distribution of retrograde and anterograde labellings within the intact cortex and within the graft was examined at light and electron microscopic levels to identify the synaptic contacts. Our findings showed that labelled contacts were less numerous within the transplant than within the intact cortex but their synaptic organization was similar: asymmetrical synaptic axo-dendritic and axo-somatic contacts. This synaptic articulation is probably supplied by a thalamic excitatory input. These results provide ultrastructural evidence of the capacity of a frontal cortical transplant placed in damaged frontal cortex of newborn rats to help reconstruction of appropriate synaptic integration within the thalamo-fronto-striate system.}, Author = {Zin-Ka-Ieu, S. and Roger, M. and Arnault, P.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:46 -0400}, Issn = {0899-0220}, Journal = {Somatosens Mot Res}, Keywords = {Cholera Toxin;Phytohemagglutinins;Animals;Synapses;Corpus Striatum;Thalamic Nuclei;Brain Tissue Transplantation;Rats;Neural Pathways;Frontal Lobe;Axons;Rats, Wistar;Fetal Tissue Transplantation;Axonal Transport;Animals, Newborn;Neurons;Immunohistochemistry;Microscopy, Electron;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't}, Medline = {20095891}, Nlm_Id = {8904127}, Number = {4}, Organization = {CNRS: UMR 6558, D{\'e}partement des Neurosciences, Laboratoire de Neurophysiologie, Universit{\'e} de Poitiers, France.}, Pages = {338-51}, Pubmed = {10632030}, Title = {The thalamo-fronto-striate system: ultrastructural evidence of appropriate synaptic integration of embryonic neurones grafted within the frontal cortex of newborn rats}, Uuid = {FE62FF2A-73A3-4539-8761-F3961FD5E10D}, Volume = {16}, Year = {1999}} @article{Zitnik:2002, Abstract = {0360-4012 Journal Article Review Review, Tutorial}, Author = {Zitnik, G. and Martin, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {J Neurosci Res}, Keywords = {01 Adult neurogenesis general;Aging/pathology/*physiology;Cell Division/physiology;Alzheimer Disease/pathology/physiopathology;Human;Brain/*pathology/physiopathology;Neurodegenerative Diseases/*pathology/physiopathology;A abstr;Stem Cells/pathology;Cell Differentiation/physiology;Support, U.S. Gov't, P.H.S.;Animals;Neurons/*pathology}, Number = {3}, Organization = {Department of Pathology, University of Washington, Seattle, Washington 98995, USA.}, Pages = {258-63}, Pubmed = {12391584}, Title = {Age-related decline in neurogenesis: old cells or old environment?}, Uuid = {0688E827-CDF1-11D9-B244-000D9346EC2A}, Volume = {70}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12391584}} @article{Ziv:2006, Abstract = {Neurogenesis is known to take place in the adult brain. This work identifies T lymphocytes and microglia as being important to the maintenance of hippocampal neurogenesis and spatial learning abilities in adulthood. Hippocampal neurogenesis induced by an enriched environment was associated with the recruitment of T cells and the activation of microglia. In immune-deficient mice, hippocampal neurogenesis was markedly impaired and could not be enhanced by environmental enrichment, but was restored and boosted by T cells recognizing a specific CNS antigen. CNS-specific T cells were also found to be required for spatial learning and memory and for the expression of brain-derived neurotrophic factor in the dentate gyrus, implying that a common immune-associated mechanism underlies different aspects of hippocampal plasticity and cell renewal in the adult brain.}, Author = {Ziv, and Ron, and Butovsky, and Landa, and Sudai, and Greenberg, and Cohen, and Kipnis, and Schwartz,}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1097-6256}, Journal = {Nat Neurosci}, Keywords = {01 Adult neurogenesis general;03 Adult neurogenesis progenitor source;11 Glia;04 Adult neurogenesis factors}, Month = {1}, Nlm_Id = {9809671}, Number = {2}, Organization = {[1] Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel. [2] These authors contributed equally to this work.}, Pages = {268-75}, Pii = {nn1629}, Pubmed = {16415867}, Title = {Immune cells contribute to the maintenance of neurogenesis and spatial learning abilities in adulthood}, Uuid = {C2104CDC-1E8A-4037-A673-A94DD0501F5E}, Volume = {9}, Year = {2006}, url = {papers/Ziv_NatNeurosci2006.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn1629}} @article{Ziv:2006a, Abstract = {The well regulated activities of microglia and T cells specific to central nervous system (CNS) antigens can contribute to the protection of CNS neural cells and their renewal from adult neural stem/progenitor cells (aNPCs). Here we report that T cell-based vaccination of mice with a myelin-derived peptide, when combined with transplantation of aNPCs into the cerebrospinal fluid (CSF), synergistically promoted functional recovery after spinal cord injury. The synergistic effect was correlated with modulation of the nature and intensity of the local T cell and microglial response, expression of brain-derived neurotrophic factor and noggin protein, and appearance of newly formed neurons from endogenous precursor-cell pools. These results substantiate the contention that the local immune response plays a crucial role in recruitment of aNPCs to the lesion site, and suggest that similar immunological manipulations might also serve as a therapeutic means for controlled migration of stem/progenitor cells to other acutely injured CNS sites.}, Author = {Ziv, Yaniv and Avidan, Hila and Pluchino, Stefano and Martino, Gianvito and Schwartz, Michal}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {T-Lymphocytes;Cell Differentiation;Wound Healing;Myelin Sheath;Animals;Carrier Proteins;Stem Cell Transplantation;Brain-Derived Neurotrophic Factor;Myelin-Associated Glycoprotein;Microglia;Vaccination;Mice, Inbred C57BL;11 Glia;research support, non-u.s. gov't;Green Fluorescent Proteins;Spinal Cord;Spinal Cord Injuries;Neurons;Mice;24 Pubmed search results 2008;Stem Cells}, Month = {8}, Nlm_Id = {7505876}, Number = {35}, Organization = {*Department of Neurobiology, Weizmann Institute of Science, 76100 Rehovot, Israel.}, Pages = {13174-9}, Pii = {0603747103}, Pubmed = {16938843}, Title = {Synergy between immune cells and adult neural stem/progenitor cells promotes functional recovery from spinal cord injury}, Uuid = {145092FB-E6E8-4951-B9A3-2409E5B70B25}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0603747103}} @article{Zoghbi:2003, Abstract = {We often think of neurodevelopmental disorders as beginning before birth, and many certainly do. A handful, however, strike many months after birth, following a period of apparently normal growth and development. Autism and Rett syndrome are two such disorders, and here I consider some of their similarities at the phenotypic and pathogenic levels. I propose that both disorders result from disruption of postnatal or experience-dependent synaptic plasticity.}, Author = {Zoghbi, Huda Y.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Human;Neuregulins;Magnetic Resonance Imaging;Animals;Synapses;DNA-Binding Proteins;Carrier Proteins;Neuronal Plasticity;Age of Onset;Phenotype;Child, Preschool;Brain;Female;Mutation;Infant;Chromosome Aberrations;21 Neurodegenerative;Male;Support, Non-U.S. Gov't;21 Neurophysiology;Neurons;Ubiquitin-Protein Ligases;Autistic Disorder;Support, U.S. Gov't, P.H.S.;Membrane Proteins;Nerve Tissue Proteins;Rett Syndrome}, Medline = {22954846}, Month = {10}, Nlm_Id = {0404511}, Number = {5646}, Organization = {Departments of Pediatrics, Neurology, and Molecular and Human Genetics, Division of Neuroscience, and Howard Hughes Medical Institute, Baylor College of Medicine, Houston, TX 77030, USA. hzoghbi\@bcm.tmc.edu}, Pages = {826-30}, Pii = {302/5646/826}, Pubmed = {14593168}, Title = {Postnatal neurodevelopmental disorders: meeting at the synapse?}, Uuid = {83380465-D390-4349-866F-A5B4EB33BF44}, Volume = {302}, Year = {2003}, url = {papers/Zoghbi_Science2003.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1089071}} @article{Zou:2001, Abstract = {The olfactory system translates myriad chemical structures into diverse odour perceptions. To gain insight into how this is accomplished, we prepared mice that coexpressed a transneuronal tracer with only one of about 1,000 different odorant receptors. The tracer travelled from nasal neurons expressing that receptor to the olfactory bulb and then to the olfactory cortex, allowing visualization of cortical neurons that receive input from a particular odorant receptor. These studies revealed a stereotyped sensory map in the olfactory cortex in which signals from a particular receptor are targeted to specific clusters of neurons. Inputs from different receptors overlap spatially and could be combined in single neurons, potentially allowing for an integration of the components of an odorant's combinatorial receptor code. Signals from the same receptor are targeted to multiple olfactory cortical areas, permitting the parallel, and perhaps differential, processing of inputs from a single receptor before delivery to the neocortex and limbic system.}, Author = {Zou, Z. and Horowitz, L. F. and Montmayeur, J. P. and Snapper, S. and Buck, L. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Journal = {Nature}, Keywords = {T;23 Technique}, Number = {6860}, Organization = {[1] Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA [2] These authors contributed equally to this work.}, Pages = {173-9.}, Title = {Genetic tracing reveals a stereotyped sensory map in the olfactory cortex}, Uuid = {CADC5A48-AA72-4AD9-AAA4-D3C1241DB115}, Volume = {414}, Year = {2001}, url = {papers/Zou_Nature2001}} @article{Zou:2006, Abstract = {In mammals, each odorant is detected by a combination of different odorant receptors. Signals from different types of receptors are segregated in the nose and the olfactory bulb, but appear to be combined in individual neurons in the olfactory cortex. Here, we report that binary odorant mixes stimulate cortical neurons that are not stimulated by their individual component odorants. We propose that cortical neurons require combinations of receptor inputs for activation and that merging the receptor codes of two odorants provides novel combinations of receptor inputs that stimulate neurons beyond those activated by the single odorants. These findings may explain why odorant mixtures can elicit novel odor percepts in humans.}, Author = {Zou, Zhihua and Buck, Linda B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1095-9203}, Journal = {Science}, Keywords = {Research Support, Non-U.S. Gov't;In Situ Hybridization, Fluorescence;Animals;Humans;Olfactory Receptor Neurons;Complex Mixtures;Research Support, U.S. Gov't, Non-P.H.S.;Mice, Inbred C57BL;RNA, Messenger;Odors;Smell;Olfactory Pathways;Neurons;Receptors, Odorant;Mice;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;Nerve Tissue Proteins;Cytoskeletal Proteins}, Month = {3}, Nlm_Id = {0404511}, Number = {5766}, Organization = {Howard Hughes Medical Institute and Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.}, Pages = {1477-81}, Pii = {311/5766/1477}, Pubmed = {16527983}, Title = {Combinatorial effects of odorant mixes in olfactory cortex}, Uuid = {1354EF88-6E27-4399-9B39-D7A782AC4DE9}, Volume = {311}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1126/science.1124755}} @article{Zovein:2006, Author = {Zovein, Ann C. and Iruela-Arispe, M. Luisa}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0027-8424}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {14 Immune;11 Glia;24 Pubmed search results 2008}, Month = {8}, Nlm_Id = {7505876}, Number = {35}, Organization = {Department of Molecular, Cell and Developmental Biology and Molecular Biology Institute, University of California, Los Angeles, CA 90095.}, Pages = {12959-60}, Pii = {0606018103}, Pubmed = {16924095}, Title = {My O'Myeloid, a tale of two lineages}, Uuid = {61C3A403-07D9-40D8-B199-2880BD7EE426}, Volume = {103}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1073/pnas.0606018103}} @article{Zufferey:1999, Abstract = {The development of cortico-cortical connections was studied in kittens deprived of vision by binocular eyelid suture during the formation of axonal arbors and synaptogenesis, i.e. between the second postnatal week and the end of the third postnatal month. Axons originating in area 17 and terminating either in ipsilateral or contralateral visual areas were visualized with biocytin. In ipsilateral areas 17 and 18, distinct clusters of branches begin to form, distally from the injection, during the second half of the first postnatal month, independently of pattern vision. More proximal clusters differentiate during the second postnatal month, and this seems to involve elimination of exuberant axonal branches. In kittens deprived of vision for 3 or more months, beginning before natural eye opening, the distal clusters regress and the proximal ones fail to differentiate. In extrastriate areas, distinct clusters of branches have segregated by the end of the second postnatal month, independently of visual experience; however, in kittens deprived of vision for 2 or more months, one of the clusters was selectively eliminated. In contralateral areas 17 and 18, we found stunted terminal arbors in kittens continuously deprived of vision. This was already noticeable at the end of the first postnatal month. Apparently, in the absence of pattern vision, most axons undergo only limited growth and do not form their characteristic terminal columns. Many of these axons are subsequently eliminated. In contrast, 8 days of vision beginning at natural eye opening and followed by visual deprivation caused a nearly normal development of intrahemispheric and interhemispheric connections. In conclusion, pattern vision appears to validate connections at early stages of their development; this validation is necessary for their further growth and differentiation that can then continue autonomously.}, Author = {Zufferey, P. D. and Jin, F. and Nakamura, H. and Tettoni, L. and Innocenti, G. M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:46 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Corpus Callosum;Sensory Deprivation;Reference Values;Cats;Not relevant;11 Glia;Vision;Animals, Newborn;Support, Non-U.S. Gov't;Visual Pathways;Animals;Cerebral Cortex;Axons}, Medline = {99388263}, Month = {8}, Nlm_Id = {8918110}, Number = {8}, Organization = {Institut de Biologie Cellulaire et de Morphologie, Lausanne, Switzerland.}, Pages = {2669-88}, Pii = {ejn683}, Pubmed = {10457164}, Title = {The role of pattern vision in the development of cortico-cortical connections}, Uuid = {81E953ED-00F8-4CDA-B79D-F81DEDAC4FCD}, Volume = {11}, Year = {1999}} @article{Zuo:1998, Abstract = {It was the first time demonstrated by us that the number of newborn neurons was increased after making lesion in forebrain of adult ring dove (Streptopelia risoria) by means of autoradiography and immunohistochemistry. Neurogenesis in the adult avian is restricted to the telencephalon. In doves with bilateral electrolytic lesion of nucleus ectostriatum (E), the mean number of proliferating cells in the lateral ventricular zone (LVZ) and newborn neurons in the forebrain increased by 1.95 times and 2.38 times respectively as compared with that in intact doves. The most remarkable increase of neurogenesis induced by nucleus ectostriatum lesions was found at the anterior- posterior level 3 (L3), where the lesion site was located. These results showed that the electrolytic brain lesion altered the distribution pattern of proliferating cells in the LVZ and resulted in increase of the number of newborn neurons in the non-VZ areas of forebrain. The changes in number and distribution pattern of proliferating cells in LVZ and newborn neurons in forebrain may be dependent on site of lesion. Studies on the relationship between proliferating cells in LVZ and newly generated neurons in non-VZ areas may help to understand the mechanism of brain plasticity and development.}, Author = {Zuo, M. X.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Cell Res}, Keywords = {Neurons/*cytology/metabolism;Telencephalon/*cytology/*injuries/metabolism;Microtubule-Associated Proteins/analysis;Comparative Study;Electrodes;Photoperiod;Animal;D-7;Nerve Tissue Proteins/analysis;DNA/biosynthesis;Vocalization, Animal/physiology;Support, Non-U.S. Gov't;tau Proteins/analysis;06 Adult neurogenesis injury induced;Pigeons/*physiology;Cell Division;Immunohistochemistry;Autoradiography;Neostriatum/*cytology}, Number = {2}, Organization = {Biology Department, Beijing Normal University, China.}, Pages = {151-8.}, Title = {The studies on neurogenesis induced by brain injury in adult ring dove}, Uuid = {D5C5544E-F9F0-4860-A0CD-F3FF752658A9}, Volume = {8}, Year = {1998}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=9669030}} @article{Zuo:2004, Abstract = {To enable vital observation of glia at the neuromuscular junction, transgenic mice were generated that express proteins of the green fluorescent protein family under control of transcriptional regulatory sequences of the human S100B gene. Terminal Schwann cells were imaged repetitively in living animals of one of the transgenic lines to show that, except for extension and retraction of short processes, the glial coverings of the adult neuromuscular synapse are stable. In other lines, subsets of Schwann cells were labeled. The distribution of label suggests that Schwann cells at individual synapses are clonally related, a finding with implications for how these cells might be sorted during postnatal development. Other labeling patterns, some present in unique lines, included astrocytes, microglia, and subsets of cerebellar Bergmann glia, spinal motor neurons, macrophages, and dendritic cells. We show that lines with labeled macrophages can be used to follow the accumulation of these cells at sites of injury.}, Author = {Zuo, Yi and Lubischer, Jane L. and Kang, Hyuno and Tian, Le and Mikesh, Michelle and Marks, Alexander and Scofield, Virginia L. and Maika, Shan and Newman, Craig and Krieg, Paul and Thompson, Wesley J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Transgenes;Animals;Humans;Macrophages;Mice, Transgenic;Mice, Inbred C57BL;Recombinant Fusion Proteins;Dendritic Cells;11 Glia;Microscopy, Fluorescence;Green Fluorescent Proteins;Schwann Cells;Cell Line;Receptors, Cholinergic;Neuromuscular Junction;Research Support, U.S. Gov't, P.H.S.;Neuroglia;Neurons;Mice;Luminescent Proteins;Research Support, N.I.H., Extramural;Adipocytes;S100 Proteins;Lens, Crystalline;Langerhans Cells}, Month = {12}, Nlm_Id = {8102140}, Number = {49}, Organization = {Section of Neurobiology, Institute for Neuroscience, University of Texas, Austin, Texas 78712, USA.}, Pages = {10999-1009}, Pii = {24/49/10999}, Pubmed = {15590915}, Title = {Fluorescent proteins expressed in mouse transgenic lines mark subsets of glia, neurons, macrophages, and dendritic cells for vital examination}, Uuid = {3EE0D1DF-FA7C-4985-BFBA-39AC11444B79}, Volume = {24}, Year = {2004}, url = {papers/Zuo_JNeurosci2004.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.3934-04.2004}} @article{Zuo:2005, Abstract = {A substantial decrease in the number of synapses occurs in the mammalian brain from the late postnatal period until the end of life. Although experience plays an important role in modifying synaptic connectivity, its effect on this nearly lifelong synapse loss remains unknown. Here we used transcranial two-photon microscopy to visualize postsynaptic dendritic spines in layer I of the barrel cortex in transgenic mice expressing yellow fluorescent protein. We show that in young adolescent mice, long-term sensory deprivation through whisker trimming prevents net spine loss by preferentially reducing the rate of ongoing spine elimination, not by increasing the rate of spine formation. This effect of deprivation diminishes as animals mature but still persists in adulthood. Restoring sensory experience after adolescent deprivation accelerates spine elimination. Similar to sensory manipulation, the rate of spine elimination decreases after chronic blockade of NMDA (N-methyl-D-aspartate) receptors with the antagonist MK801, and accelerates after drug withdrawal. These studies of spine dynamics in the primary somatosensory cortex suggest that experience plays an important role in the net loss of synapses over most of an animal's lifespan, particularly during adolescence.}, Author = {Zuo, Yi and Yang, Guang and Kwon, Elaine and Gan, Wen-Biao B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1476-4687}, Journal = {Nature}, Keywords = {Touch;Animals;Synapses;Aging;Dizocilpine Maleate;Dendritic Spines;Mice, Transgenic;Vibrissae;Sexual Maturation;Physical Stimulation;23 Technique;Time Factors;Research Support, U.S. Gov't, P.H.S.;Animals, Newborn;Somatosensory Cortex;Mice;24 Pubmed search results 2008;Research Support, N.I.H., Extramural;16 Barrels;Receptors, N-Methyl-D-Aspartate}, Month = {7}, Nlm_Id = {0410462}, Number = {7048}, Organization = {Skirball Institute, Department of Physiology and Neuroscience, New York University School of Medicine, 540 First Avenue, New York, New York 10016, USA.}, Pages = {261-5}, Pii = {nature03715}, Pubmed = {16015331}, Title = {Long-term sensory deprivation prevents dendritic spine loss in primary somatosensory cortex}, Uuid = {C14A7AEE-2047-472F-97F5-AE7B26EAE6A5}, Volume = {436}, Year = {2005}, url = {papers/Zuo_Nature2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nature03715}} @article{Zupanc:2003, Abstract = {Persistence of radial glia within the adult central nervous system is a widespread phenomenon among fish. Based on a series of studies in the teleost species Apteronotus leptorhynchus, we propose that one function of this persistence is the involvement of radial glia in adult neurogenesis, i.e., the generation and further development of new neurons in the adult central nervous system. In particular, evidence has been obtained for the involvement of radial glia in the guidance of migrating young neurons in both the intact and the regenerating brain; for a possible role as precursor cells from which new neurons arise; and for its role as a source of trophic substances promoting the generation, differentiation, and/or survival of new neurons. These functions contribute not only to the potential of the intact brain to generate new neurons continuously, and of the injured brain to replace damaged cells by newly generated ones, but they also provide an essential part of the cellular substrate of behavioral plasticity. 0894-1491 Journal Article Review Review, Tutorial}, Author = {Zupanc, G. K. and Clint, S. C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Glia}, Keywords = {Brain/cytology/*growth &development;01 Adult neurogenesis general;Neuronal Plasticity/physiology;Neurons/*cytology/physiology;Fishes/anatomy &histology/*growth &development;Stem Cells/*cytology/physiology;Neuroglia/*cytology/physiology;Cell Differentiation/physiology;Animals;Nerve Regeneration/physiology;A pdf;Cell Movement/physiology}, Number = {1}, Organization = {School of Engineering and Science, International University Bremen, Bremen, Germany. g.zupanc\@iu-bremen.de}, Pages = {77-86}, Pubmed = {12761870}, Title = {Potential role of radial glia in adult neurogenesis of teleost fish}, Uuid = {3EABF79B-60A5-4AF7-AD0A-12A387FD0D6B}, Volume = {43}, Year = {2003}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12761870}} @article{abd-el-Basset:1995, Abstract = {We examined the effect of bacterial wall lipopolysaccharide (LPS), a strong inflammatory agent, on the morphology, cell motility, cytoskeletal organization, and phagocytic activity of microglia in tissue cultures initiated from neopallia of newborn C3H/OuJ mice. Normally, the microglia in our cultures are non-migratory and Mac-1 positive, have ameboid cell morphology, no polarity, many short processes that extend into lamellipodia in opposing directions, and undulating cell membrane projections. When 1-5 micrograms/ml LPS is added to such cultures, some cells acquire polarity by forming a large lamellipodium and begin to migrate. Two hours later migration ceases; the membrane undulations stop; and the cells become non-polar, assume a large, round, flat shape, and gradually develop many microspikes all over the cell body. Those cells that do not transform into large, round, flat cells enlarge and extend numerous lamellipodia in opposing directions. We found that the cytoskeleton of microglia is composed of actin, vimentin-containing intermediate filaments (IF) and microtubules (MT). Vimentin-containing IF and MT form dense networks that radiate into the cell periphery, whereas F-actin is diffusely arranged throughout the cytoplasm. The LPS-treated cells show changes in the organization of the main components of the cytoskeleton. F-actin is reorganized by the formation of bundles underneath and parallel to the cell membrane and other bundles projecting into the cores of the microspikes. The vimentin-containing IF dense network reorganizes into two condensed rings, with fine strands of IF extended between the two rings and the MT networks become less dense and extend throughout the cytoplasm. The LPS treatment potentiates the phagocytic activity of the microglia. However, approximately 30\%of microglia lose the expression of MHC class II antigens.}, Author = {abd-el-Basset, E. and Fedoroff, S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0360-4012}, Journal = {J Neurosci Res}, Keywords = {Mice, Inbred Strains;24 Pubmed search results 2008;Research Support, Non-U.S. Gov't;Immunohistochemistry;Antigens;Microtubules;Antibodies, Monoclonal;11 Glia;Microglia;Animals, Newborn;Mice;Cells, Cultured;Animals;Actins;Lipopolysaccharides}, Medline = {95379100}, Month = {6}, Nlm_Id = {7600111}, Number = {2}, Organization = {Department of Anatomy, College of Medicine, University of Saskatchewan, Saskatoon, Canada.}, Pages = {222-37}, Pubmed = {7650758}, Title = {Effect of bacterial wall lipopolysaccharide (LPS) on morphology, motility, and cytoskeletal organization of microglia in cultures}, Uuid = {B0EA318C-BAAB-11DA-93EA-000D9346EC2A}, Volume = {41}, Year = {1995}, Bdsk-Url-1 = {http://dx.doi.org/10.1002/jnr.490410210}} @article{dOrsi:2004, Abstract = {OBJECTIVES: Little is known about the long term outcome of patients with periventricular nodular heterotopia (PNH) and epilepsy, particularly the course of seizures. This study investigated the electroclinical and prognostic features of 16 patients with PNH. METHODS: Of 120 patients with epilepsy and malformations of cortical development, 16 had PNH. Of these, eight patients had periventricular nodules only (simple PNH) and eight also presented with other cortical or cerebral malformations (subcortical heterotopia; polymicrogyria; focal dysplasia; schizencephaly; cortical infolding; agenesis of the corpus callosum; mega cisterna magna and cerebellar atrophy) (PNH plus). All patients underwent clinical, neurophysiological, and MRI investigation. The mean follow up was 17.3 years (2-40 years). RESULTS: Two electroclinical patterns emerged: (1) The first pattern, associated with simple PNH, was characterised by normal intelligence and seizures, usually partial, which began during the second decade of life. The seizures never became frequent and tended to disappear or become very rare. The EEG showed focal abnormalities. (2) The second pattern, associated with PNH plus, was characterised by mental retardation and seizures that began during the first decade of life. The seizures were very frequent in most cases and sudden drops were observed in six patients. Seizures were medically refractory in four patients. The EEG showed focal and bisynchronous abnormalities. CONCLUSIONS: Two groups of PNH patients with different electroclinical and neuroradiological features can be identified after a long term follow up. The presence of other types of cortical or cerebral malformations, in addition to periventricular nodules, determines a poor prognosis.}, Author = {d'Orsi, G. and Tinuper, P. and Bisulli, F. and Zaniboni, A. and Bernardi, B. and Rubboli, G. and Riva, R. and Michelucci, R. and Volpi, L. and Tassinari, C. A. and Baruzzi, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:29 -0400}, Issn = {0022-3050}, Journal = {J Neurol Neurosurg Psychiatry}, Keywords = {Outcome Assessment (Health Care);Magnetic Resonance Imaging;Follow-Up Studies;Humans;Middle Aged;Prognosis;Comparative Study;21 Epilepsy;Female;Epilepsy;Male;Abnormalities, Multiple;Cerebral Cortex;21 Neurophysiology;Retrospective Studies;Adult;24 Pubmed search results 2008;Choristoma;Electroencephalography;Adolescent}, Month = {6}, Nlm_Id = {2985191R}, Number = {6}, Organization = {Department of Neurological Sciences, University of Bologna, Bologna, Italy.}, Pages = {873-8}, Pubmed = {15146004}, Title = {Clinical features and long term outcome of epilepsy in periventricular nodular heterotopia. Simple compared with plus forms}, Uuid = {1A36D0D7-EFEE-4130-9F34-7F21B6ED626E}, Volume = {75}, Year = {2004}} @article{Groot:1992, Abstract = {The origin and nature of brain macrophages and microglial cells in the mouse central nervous system (CNS) were investigated. First, the expression and localization of determinants recognized by the different monoclonal antibodies (mAbs) MOMA-1, Mac-1-alpha, and F4/80 (raised against cells of the mononuclear phagocyte system) were immunohistochemically studied in the developing and adult mouse brain. In order to clarify the origin of brain macrophages and microglial cells, we used bacteriophage lambda transgenic mice as donors for bone marrow transplantations in recipient mice of different ages. During ontogeny, numerous MOMA-1-, Mac-1-alpha-, and F4/80-positive blood monocyte-derived brain macrophages (amoeboid microglia) infiltrated the CNS parenchyma. These brain macrophages gradually disappeared from the brain parenchyma at postnatal day 7 (P7). From P17 on, Mac-1-alpha- and F4/80-positive cells were detected within the brain parenchyma with the morphology of resting microglial cells. Transitional forms between brain macrophages and "resting" microglia were not observed in the developing brain. Combined non-radioactive in situ hybridization and immunohistochemistry revealed many MOMA-1-positive bone marrow-derived brain macrophages that were located in the leptomeninges, the ventricles, and occasionally the blood vessel walls. These results show that brain macrophages are of bone marrow origin. Many "resting" microglial cells were detected in the brain, mainly in the white matter. It appeared that about 10\%of these cells displayed the transgenic signal. This result indicates that the majority of "resting" microglial cells are of local, presumably neuroectodermal, origin.}, Author = {de Groot, C. J. and Huppes, W. and Sminia, T. and Kraal, G. and Dijkstra, C. D.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0894-1491}, Journal = {Glia}, Keywords = {Fetus;Research Support, Non-U.S. Gov't;Immune Sera;Animals;Macrophages;Bone Marrow Transplantation;Immunoenzyme Techniques;Brain;Mice, Transgenic;Staining and Labeling;11 Glia;Phagocytes;Embryonic and Fetal Development;Cell Line;Bone Marrow Cells;Animals, Newborn;Antibodies, Monoclonal;Neuroglia;Mice;Nucleic Acid Hybridization}, Medline = {93100083}, Nlm_Id = {8806785}, Number = {4}, Organization = {Department of Cell Biology, Vrije Universiteit, Amsterdam, The Netherlands.}, Pages = {301-9}, Pubmed = {1281462}, Title = {Determination of the origin and nature of brain macrophages and microglial cells in mouse central nervous system, using non-radioactive in situ hybridization and immunoperoxidase techniques}, Uuid = {337F068C-B22D-4039-9C92-85FFD4187C98}, Volume = {6}, Year = {1992}} @article{Jong:2005, Abstract = {Whenever neurons in the CNS are injured, microglia become activated. In addition to local activation, microglia remote from the primary lesion site are stimulated. Because this so-called secondary activation of microglia is instrumental for long-term changes after neuronal injury, it is important to understand how microglia activity is controlled. The remote activation of microglia implies that the activating signals are transported along neuronal projections. However, the identity of these signals has not yet been identified. It is shown here that glutamate-treated neurons rapidly express and release the chemokine CCL21. We also provide evidence that neuronal CCL21 is packed in vesicles and transported throughout neuronal processes to reach presynaptic structures. Chemotaxis assays show that functional CCL21 is released from endangered neurons and activate microglia via the chemokine receptor CXCR3. Based on these findings, we suggest that neuronal CCL21 is important in directed neuron-microglia signaling and that this communication could account for the remote activation of microglia, far distant from a primary lesion.}, Author = {de Jong, Eiko K. and Dijkstra, Ineke M. and Hensens, Marjolein and Brouwer, Nieske and van Amerongen, Machteld and Liem, Robert S. B. and Boddeke, Hendrikus W. G. M. and Biber, Knut}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {11 Glia}, Month = {8}, Nlm_Id = {8102140}, Number = {33}, Organization = {Department of Medical Physiology, University of Groningen, 9713 AV Groningen, The Netherlands.}, Pages = {7548-57}, Pii = {25/33/7548}, Pubmed = {16107642}, Title = {Vesicle-mediated transport and release of CCL21 in endangered neurons: a possible explanation for microglia activation remote from a primary lesion}, Uuid = {AC74FB10-C9CE-4F1B-94D5-75E0084EAF92}, Volume = {25}, Year = {2005}, url = {papers/Jong_JNeurosci2005.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.1019-05.2005}} @article{Villers-Sidani:2008, Abstract = {During early brain development and through 'adult' experience-dependent plasticity, neural circuits are shaped to represent the external world with high fidelity. When raised in a quiet environment, the rat primary auditory cortex (A1) has a well-defined 'critical period', lasting several days, for its representation of sound frequency. The addition of environmental noise extends the critical period duration as a variable function of noise level. It remains unclear whether critical period closure should be regarded as a unified, externally gated event that applies for all of A1 or if it is controlled by progressive, local, activity-driven changes in this cortical area. We found that rearing rats in the presence of a spectrally limited noise band resulted in the closure of the critical period for A1 sectors representing the noise-free spectral bands, whereas the critical period appeared to remain open in noise-exposed sectors, where the cortex was still functionally and physically immature.}, Author = {de Villers-Sidani, Etienne and Simpson, Kimberly L. and Lu, Y-F F. and Lin, Rick C. S. and Merzenich, Michael M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1546-1726}, Journal = {Nat Neurosci}, Keywords = {Animals;Rats;Recovery of Function;Female;Rats, Sprague-Dawley;Reaction Time;research support, non-u.s. gov't;Time Factors;Critical Period (Psychology);Hearing Tests;Animals, Newborn;Noise;Parvalbumins;Neurons;research support, n.i.h., extramural;Auditory Cortex;24 Pubmed search results 2008;Acoustic Stimulation;Spectrum Analysis;Electrodes, Implanted;Brain Mapping}, Month = {8}, Nlm_Id = {9809671}, Number = {8}, Organization = {W.M. Keck Center for Integrative Neuroscience, Coleman Laboratory, Department of Otolaryngology, University of California, San Francisco, 513 Parnassus Avenue, Room HSE-808, Box 0732, San Francisco, California 94143, USA. etienne\@phy.ucsf.edu}, Pages = {957-65}, Pii = {nn.2144}, Pubmed = {18604205}, Title = {Manipulating critical period closure across different sectors of the primary auditory cortex}, Uuid = {9B811407-F134-4A51-A3CA-E6A506A91089}, Volume = {11}, Year = {2008}, url = {papers/Villers-Sidani_NatNeurosci2008.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/nn.2144}} @article{Rio:2002, Abstract = {Severed adult CNS axons can extend over long distances when a permissive 'milieu', such as grafted Schwann cells or ensheathing cells, is provided. Moreover, functional blocking of endogenous inhibitory factors, such as Nogo-A or proteoglycans, enhances the regeneration of axotomized neurons. Here we examine whether guidance cues available during the development of axonal pathways could also potentiate the regeneration of lesioned adult circuits. The Cajal-Retzius cells in the hippocampus are transient pioneer neurons that guide entorhino-hippocampal afferents to their target layers. By using an in vitro model of axotomy of the entorhino-hippocampal pathway we show that Cajal-Retzius cells triggered the regeneration of the axotomized entorhino-hippocampal pathway. Furthermore, the regrowth induced by Cajal-Retzius cells was robust and its pattern was indistinguishable from that of the unlesioned entorhino-hippocampal pathway. Thus, regenerating axons regrew in a layer-specific fashion towards the appropriate target layers, making synaptic contacts with target pyramidal neurons. Interestingly, the ability of lesioned entorhinal axons to regrow was maintained for at least 9 days after axotomy. These results show that the growth-promoting cells controlling the development of neural circuits will be a relevant approach to promoting the regeneration of lesioned adult CNS pathways.}, Author = {del R{\'\i}o, Jos{\'e} A. and Sol{\'e}, Marta and Borrell, V{\'\i}ctor and Mart{\'\i}nez, Albert and Soriano, Eduardo}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Research Support, Non-U.S. Gov't;Presynaptic Terminals;Lysine;Animals;Coculture Techniques;Aging;Neuronal Plasticity;Neural Pathways;Cell Communication;Entorhinal Cortex;Hippocampus;Pyramidal Cells;Organ Culture Techniques;Nerve Regeneration;Animals, Newborn;Mice, Inbred Strains;Axotomy;Body Patterning;Mice;24 Pubmed search results 2008;Microscopy, Electron;Stem Cells;Cues;Growth Cones;Growth Substances}, Medline = {22095224}, Month = {6}, Nlm_Id = {8918110}, Number = {12}, Organization = {Department of Cell Biology, Faculty of Biology, and Neuroscience Research Center (CERN), University of Barcelona, Diagonal 645, 08028 Barcelona, Spain. jario\@porthos.bio.ub.es}, Pages = {1881-90}, Pii = {2027}, Pubmed = {12099894}, Title = {Involvement of Cajal-Retzius cells in robust and layer-specific regeneration of the entorhino-hippocampal pathways}, Uuid = {D21EEB28-BCD7-445C-AC14-A1D4393DF0CE}, Volume = {15}, Year = {2002}} @article{Portes:1998, Abstract = {X-SCLH/LIS syndrome is a neuronal migration disorder with disruption of the six-layered neocortex. It consists of subcortical laminar heterotopia (SCLH, band heterotopia, or double cortex) in females and lissencephaly (LIS) in males, leading to epilepsy and cognitive impairment. We report the characterization of a novel CNS gene encoding a 40 kDa predicted protein that we named Doublecortin and the identification of mutations in four unrelated X-SCLH/LIS cases. The predicted protein shares significant homology with the N-terminal segment of a protein containing a protein kinase domain at its C-terminal part. This novel gene is highly expressed during brain development, mainly in fetal neurons including precursors. The complete disorganization observed in lissencephaly and heterotopia thus seems to reflect a failure of early events associated with neuron dispersion.}, Author = {des Portes, V. and Pinard, J. M. and Billuart, P. and Vinet, M. C. and Koulakoff, A. and Carri{\'e}, A. and Gelot, A. and Dupuis, E. and Motte, J. and Berwald-Netter, Y. and Catala, M. and Kahn, A. and Beldjord, C. and Chelly, J.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:39 -0400}, Issn = {0092-8674}, Journal = {Cell}, Keywords = {Epilepsy;24 Pubmed search results 2008;Male;Cerebral Cortex;Peptides;10 Development;Transcription, Genetic;Base Sequence;Cell Movement;X Chromosome;Central Nervous System;Sex Chromosome Aberrations;Gene Expression;Molecular Sequence Data;Child, Preschool;Sequence Tagged Sites;Microtubule-Associated Proteins;Chromosomes, Artificial, Yeast;Chromosome Mapping;Mutation;Neuropeptides;Adolescent;Amino Acid Sequence;Pedigree;Female;Family Health;Syndrome;DNA, Complementary;research support, non-u.s. gov't;Genes;Humans;Neurons;10 genetics malformation;Sequence Homology, Amino Acid}, Month = {1}, Nlm_Id = {0413066}, Number = {1}, Organization = {INSERM U129-ICGM, Facult{\'e} de M{\'e}decine Cochin, Paris, France.}, Pages = {51-61}, Pubmed = {9489699}, Title = {A novel CNS gene required for neuronal migration and involved in X-linked subcortical laminar heterotopia and lissencephaly syndrome}, Uuid = {B90CA395-BE10-41AF-A4F8-FEC9FB0CAC6A}, Volume = {92}, Year = {1998}} @article{Portes:2002, Abstract = {We report the case of a female suffering from resistant partial seizures, which were related to 'cryptogenic' epilepsy, as the cerebral cortex was considered normal on the initial MRI images. As her son is mentally retarded and has a pachygyria, the doublecortin gene, usually involved in band heterotopia or lissencephaly, was screened for mutations. A missense mutation was identified, shared by both the son and his mother, and a subtle discontinuous subcortical heterotopia was subsequently detected on the mother's MRI. The pathophysiology of epilepsy in this woman is discussed in the light of the role of doublecortin, not only in neuronal migration, but also in axonal growth and dendritic connectivity.}, Author = {des Portes, V. and Abaoub, L. and Joannard, A. and Souville, I. and Francis, F. and Pinard, J. M. and Chelly, J. and Beldjord, C. and Jouk, P. S.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1059-1311}, Journal = {Seizure}, Keywords = {24 Pubmed search results 2008;Epilepsy, Complex Partial;10 Development;research support, non-u.s. gov't;Adult;Magnetic Resonance Imaging;Point Mutation;Female;Neuropeptides;Child, Preschool;10 genetics malformation;1-Alkyl-2-acetylglycerophosphocholine Esterase;Humans;Male;Cerebral Cortex;Microtubule-Associated Proteins;case reports}, Month = {6}, Nlm_Id = {9306979}, Number = {4}, Organization = {Service de neurop{\'e}diatrie, H\^{o}pital Saint Vincent-de-Paul, Paris, France. desportes\@cochin.inserm.fr}, Pages = {273-7}, Pii = {S1059131101906077}, Pubmed = {12027577}, Title = {So-called 'cryptogenic' partial seizures resulting from a subtle cortical dysgenesis due to a doublecortin gene mutation}, Uuid = {CF731140-005A-47C7-94DE-6B6C3CF23FEA}, Volume = {11}, Year = {2002}, url = {papers/Portes_Seizure2002.pdf}, Bdsk-Url-1 = {http://dx.doi.org/10.1053/seiz.2001.0607}} @article{Eitzen:1998, Abstract = {Recent in vitro experiments suggest that neurotoxicity of the prion protein is dependent on the presence of microglia. We have studied 11 cases of Creutzfeldt-Jakob disease (CJD) using immunocytochemistry in combination with computerized image analysis to clarify the relationship between spongiform change and microglial activation. MHC class II-positive microglia were almost exclusively confined to cortical gray matter where the neuropil area occupied by these cells exceeded that of controls more than 350-fold. In cortical regions with a bimodal distribution of spongiform degeneration, the presence of class II-positive microglia correlated well with the presence of vacuolation in layer V, but significantly less with spongiform change in layers II and III. In areas where spongiform degeneration affected the entire depth of the cortex, activated microglia were predominantly located in the inner one-half of the cortex or were evenly distributed throughout all cortical laminae. Here, microglia exhibited atypical, tortuous cell processes and occasionally intracytoplasmic vacuoles, suggesting that microglia themselves may become a disease target. Taken together, our results provide indirect evidence against an early causative involvement of microglia in the development of spongiform change. At later stages, however, diseased microglia could produce harmful factors which mediate both astrogliosis and neuronal injury.}, Author = {v Eitzen, U. and Egensperger, R. and K{\"o}sel, S. and Grasbon-Frodl, E. M. and Imai, Y. and Bise, K. and Kohsaka, S. and Mehraein, P. and Graeber, M. B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:30 -0400}, Issn = {0022-3069}, Journal = {J Neuropathol Exp Neurol}, Keywords = {Creutzfeldt-Jakob Syndrome;DNA-Binding Proteins;Research Support, Non-U.S. Gov't;Aged;Calcium-Binding Proteins;Image Processing, Computer-Assisted;Female;Aged, 80 and over;Histocompatibility Antigens Class II;Immunochemistry;Middle Aged;Microglia;11 Glia;Humans;Brain;Male;case reports}, Medline = {98260844}, Month = {3}, Nlm_Id = {2985192R}, Number = {3}, Organization = {Institute of Neuropathology, Reference Center for Neurodegenerative Disorders, Ludwig-Maximilians-University, Munich, Germany.}, Pages = {246-56}, Pubmed = {9600217}, Title = {Microglia and the development of spongiform change in Creutzfeldt-Jakob disease}, Uuid = {2B96B203-C2B8-4146-8761-F3DAD8C3AE70}, Volume = {57}, Year = {1998}} @article{Furth:1979, Abstract = {In this study human mononuclear phagocytes from the bone marrow (promonocytes and monocytes), peripheral blood monocytes, and tissue macrophages from the skin and the peritoneal cavity were studied with respect to their morphological, cytochemical, and functional characteristics, cell surface receptors, and 3H-thymidine incorporation in vitro. The results show similarities between mononuclear phagocytes of the three body compartments with respect to esterase staining, the presence of peroxidase-positive granules, the presence of IgG and C receptors, and pinocytic and phagocytic activity. Promonocytes are the most immature mononuclear phagocytes identified in human bone marrow, and since about 80\%of these cells incorporate 3H-thymidine, they are actively dividing cells. Monocytes, whether in bone marrow or the peripheral blood, and both skin and peritoneal macrophages label minimally with 3H-thymidine and thus are nondividing cells. Since the characteristics of mononuclear phagocytes in man and mouse do not diverge greatly, it is probable that the cell sequence based on in vitro and in vivo 3H-thymidine labeling studies in the mouse holds for man as well. The successive stages of development of the human mononuclear phagocyte cell line will then be as follows: monoblasts (not yet characterized in man) divide to form promonocytes, and these cells in turn divide and give rise to monocytes that do not divide further; they leave the bone marrow, circulate in the peripheral blood, and finally become macrophages in the various tissues.}, Author = {van Furth, R. and Raeburn, J. A. and van Zwet, T. L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0006-4971}, Journal = {Blood}, Keywords = {Monocytes;Binding Sites;Phagocytes;Ascitic Fluid;Bone Marrow Cells;11 Glia;Endocytosis;Macrophages;Skin;Humans;Mitosis}, Medline = {79210039}, Month = {8}, Nlm_Id = {7603509}, Number = {2}, Pages = {485-500}, Pubmed = {454850}, Title = {Characteristics of human mononuclear phagocytes}, Uuid = {502624DF-82A9-4C9B-A618-1828DC298965}, Volume = {54}, Year = {1979}} @article{Praag:1999, Abstract = {Exposure to an enriched environment increases neurogenesis in the dentate gyrus of adult rodents. Environmental enrichment, however, typically consists of many components, such as expanded learning opportunities, increased social interaction, more physical activity and larger housing. We attempted to separate components by assigning adult mice to various conditions: water-maze learning (learner), swim-time- yoked control (swimmer), voluntary wheel running (runner), and enriched (enriched) and standard housing (control) groups. Neither maze training nor yoked swimming had any effect on bromodeoxyuridine (BrdU)-positive cell number. However, running doubled the number of surviving newborn cells, in amounts similar to enrichment conditions. Our findings demonstrate that voluntary exercise is sufficient for enhanced neurogenesis in the adult mouse dentate gyrus.}, Author = {van Praag, H. and Kempermann, G. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Journal = {Nat Neurosci}, Keywords = {A-8a;01 Adult neurogenesis general;Cell Division/physiology;Swimming/physiology;Cell Survival/physiology;Female;Mice, Inbred C57BL;Maze Learning/physiology;Animal;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Bromodeoxyuridine;Mice;Dentate Gyrus/*cytology/*growth &development;Running/*physiology}, Number = {3}, Organization = {Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, California 92037, USA.}, Pages = {266-70.}, Title = {Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus}, Uuid = {517DF153-60AE-416A-A481-2515D22791FC}, Volume = {2}, Year = {1999}, url = {papers/Praag_NatNeurosci1999.pdf}} @article{Praag:2002, Abstract = {There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.}, Author = {van Praag, Henriette and Schinder, Alejandro F. and Christie, Brian R. and Toni, Nicolas and Palmer, Theo D. and Gage, Fred H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Aging;Synapses;Cell Differentiation;Luminescent Proteins;Research Support, Non-U.S. Gov't;Female;Dentate Gyrus;Mice, Inbred C57BL;Research Support, U.S. Gov't, P.H.S.;Neural Pathways;Cell Division;Green Fluorescent Proteins;Mice;Animals;Membrane Potentials;Neurons;Genetic Vectors}, Medline = {21864715}, Month = {2}, Nlm_Id = {0410462}, Number = {6875}, Organization = {Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. vanpraag\@salk.edu}, Pages = {1030-4}, Pii = {4151030a}, Pubmed = {11875571}, Title = {Functional neurogenesis in the adult hippocampus}, Uuid = {FBEBE53E-D067-11DA-8A8C-000D9346EC2A}, Volume = {415}, Year = {2002}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/4151030a}} @article{Praag:1999a, Abstract = {Running increases neurogenesis in the dentate gyrus of the hippocampus, a brain structure that is important for memory function. Consequently, spatial learning and long-term potentiation (LTP) were tested in groups of mice housed either with a running wheel (runners) or under standard conditions (controls). Mice were injected with bromodeoxyuridine to label dividing cells and trained in the Morris water maze. LTP was studied in the dentate gyrus and area CA1 in hippocampal slices from these mice. Running improved water maze performance, increased bromodeoxyuridine-positive cell numbers, and selectively enhanced dentate gyrus LTP. Our results indicate that physical activity can regulate hippocampal neurogenesis, synaptic plasticity, and learning.}, Author = {van Praag, H. and Christie, B. R. and Sejnowski, T. J. and Gage, F. H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {Proc Natl Acad Sci U S A}, Keywords = {Learning/*physiology;Long-Term Potentiation/*physiology;Immunohistochemistry;Female;*Physical Conditioning, Animal;Mice, Inbred C57BL;Animal;04 Adult neurogenesis factors;Support, U.S. Gov't, P.H.S.;Support, Non-U.S. Gov't;Mice;Dentate Gyrus/*cytology/physiology;C abstr}, Number = {23}, Organization = {Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.}, Pages = {13427-31.}, Title = {Running enhances neurogenesis, learning, and long-term potentiation in mice}, Uuid = {2EBE2001-1D62-46E6-A64F-80FC108DA9AF}, Volume = {96}, Year = {1999}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&dopt=r&uid=10557337%20http://www.pnas.org/cgi/content/full/96/23/13427%20http://www.pnas.org/cgi/content/abstract/96/23/13427}} @article{Rooijen:1997, Abstract = {Macrophages play an important role in host defense reactions, for example, by phagocytosis of particulate materials. This process also results in the rapid removal of targeting devices such as liposomes and adenovirus vectors and of non-autologous grafted cells and materials. Another aspect of macrophage function is their production and secretion of proinflammatory cytokines. Transient and organ-specific suppression of macrophage function by liposome-mediated manipulation has been shown to improve the efficacy of drug and gene targeting and to reduce the symptoms of inflammatory reactions.}, Author = {van Rooijen, N. and Bakker, J. and Sanders, A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0167-7799}, Journal = {Trends Biotechnol}, Keywords = {Organ Specificity;Gene Transfer Techniques;23 Technique;Biotechnology;Liposomes;Inflammation;Drug Carriers;Graft Survival;11 Glia;In Vitro;Macrophages;review, tutorial;Humans;Animals;24 Pubmed search results 2008;Mice;review}, Medline = {97304689}, Month = {5}, Nlm_Id = {8310903}, Number = {5}, Organization = {Department of Cell Biology and Immunology, Faculty of Medicine, Vrije Universiteit, Amsterdam, The Netherlands. N.van\_Rooijen.cell\@med.vu.nl}, Pages = {178-85}, Pii = {S0167779997010196}, Pubmed = {9161052}, Title = {Transient suppression of macrophage functions by liposome-encapsulated drugs}, Uuid = {A2A8DEF6-CED0-11D9-B244-000D9346EC2A}, Volume = {15}, Year = {1997}, url = {papers/Rooijen_TrendsBiotechnol1997.pdf}} @article{Rossum:2002, Abstract = {We model the propagation of neural activity through a feedforward network consisting of layers of integrate-and-fire neurons. In the presence of a noisy background current and spontaneous background firing, firing rate modulations are transmitted linearly through many layers, with a delay proportional to the synaptic time constant and with little distortion. Single neuron properties and firing statistics are in agreement with physiological data. The proposed mode of propagation allows for fast computation with population coding based on firing rates, as is demonstrated with a local motion detector.}, Author = {van Rossum, Mark C. W. and Turrigiano, Gina G. and Nelson, Sacha B.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:40 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {Synapses;research support, u.s. gov't, p.h.s. ;Neural Networks (Computer);21 Neurophysiology;research support, non-u.s. gov't ;Models, Neurological;Computer Simulation;Reproducibility of Results;research support, u.s. gov't, non-p.h.s. ;Motion Perception;Sensory Thresholds;Synaptic Transmission;24 Pubmed search results 2008;Neurons}, Month = {3}, Nlm_Id = {8102140}, Number = {5}, Organization = {Department of Biology, Brandeis University, Waltham, Massachusetts 02454-9110, USA. vrossum\@brandeis.edu}, Pages = {1956-66}, Pii = {22/5/1956}, Pubmed = {11880526}, Title = {Fast propagation of firing rates through layered networks of noisy neurons}, Uuid = {4B5598BD-E83F-479E-A346-AC8BAD3C918C}, Volume = {22}, Year = {2002}} @article{Vliet:2005, Abstract = {PURPOSE: Overexpression of multidrug transporters may play a role in the development of pharmacoresistance by decreasing extracellular drug levels in the brain. However, it is not known whether overexpression is due to an initial insult or evolves more gradually because of recurrent spontaneous seizures. In the present study, we investigated the expression of different multidrug transporters during epileptogenesis in the rat. In addition, we determined whether these transporters affected phenytoin (PHT) distribution in the brain. METHODS: Expression of multidrug resistance-associated proteins MRP1 and MRP2 and breast cancer-resistance protein (BCRP) was examined after electrically induced status epilepticus (SE) by immunocytochemistry and Western blot analysis. Brain/blood PHT levels were determined by high-performance liquid chromatography (HPLC) analysis in the presence and absence of the MRP inhibitor probenecid. RESULTS: Shortly after SE, MRP1, MRP2, and BCRP were upregulated in astrocytes within several limbic structures, including hippocampus. In chronic epileptic rats, these proteins were overexpressed in the parahippocampal cortex, specifically in blood vessels and astrocytes surrounding these vessels. Overexpression was related to the occurrence of SE and was present mainly in rats with a high seizure frequency. Brain PHT levels were significantly lower in epileptic rats compared with control rats, but pharmacologic inhibition of MRPs increased the PHT levels. CONCLUSIONS: Overexpression of MRP and BCRP was induced by SE as well as recurrent seizures. Moreover, overexpression was associated with lower PHT levels in the brain, which was reversed through inhibition of MRPs. These data suggest that administration of antiepileptic drugs in combination with specific inhibitors for multidrug transporters may be a promising therapeutic strategy in pharmacoresistant patients.}, Author = {van Vliet, Erwin A. and Redeker, Sandra and Aronica, Eleonora and Edelbroek, Peter M. and Gorter, Jan A.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0013-9580}, Journal = {Epilepsia}, Keywords = {Anticonvulsants;Electric Stimulation;Tissue Distribution;Humans;Animals;Rats;Neoplasm Proteins;07 Excitotoxicity Apoptosis;Brain;Epilepsy;Rats, Sprague-Dawley;ATP-Binding Cassette Transporters;Probenecid;Chronic Disease;Male;Phenytoin;Multidrug Resistance-Associated Proteins;Status Epilepticus;Drug Resistance, Multiple;Membrane Transport Proteins;24 Pubmed search results 2008;Recurrence;Research Support, Non-U.S. Gov't}, Month = {10}, Nlm_Id = {2983306R}, Number = {10}, Organization = {Epilepsy Institute of the Netherlands (SEIN), Heemstede, the Netherlands.}, Pages = {1569-80}, Pii = {EPI250}, Pubmed = {16190927}, Title = {Expression of multidrug transporters MRP1, MRP2, and BCRP shortly after status epilepticus, during the latent period, and in chronic epileptic rats}, Uuid = {AF896A2B-C856-4E33-828A-4E2F323763A2}, Volume = {46}, Year = {2005}, Bdsk-Url-1 = {http://dx.doi.org/10.1111/j.1528-1167.2005.00250.x}} @article{Eijnde:1999, Abstract = {Apoptosis is a critical cellular event during several stages of neuronal development. Recently, we have shown that biotinylated annexin V detects apoptosis in vivo in various cell lineages of a wide range of species by binding to phosphatidylserines that are exposed at the outer leaflet of the plasma membrane. In the present study, we tested the specificity by which annexin V binds apoptotic neurons, and subsequently investigated developmental cell death in the central and peripheral nervous system of early mouse embryos at both the cellular and histological level, and compared the phagocytic clearance of apoptotic neurons with that of apoptotic mesodermal cells. Our data indicate: (i) that biotinylated annexin V can be used as a sensitive marker that detects apoptotic neurons, including their extensions at an early stage during development; (ii) that apoptosis plays an important part during early morphogenesis of the central nervous system, and during early quantitative matching of brain-derived neurotrophic factor and neurotrophic factor 3 responsive postmitotic large clear neurons in the peripheral ganglia with their projection areas; and (iii) that apoptotic neurons are removed by a process that differs from classical phagocytosis of non-neuronal tissues.}, Author = {van den Eijnde, S. M. and Lips, J. and Boshart, L. and Vermeij-Keers, C. and Marani, E. and Reutelingsperger, C. P. and De Zeeuw, C. I.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Annexin V;Phagocytosis;Animals;Rats;Ganglia, Spinal;Apoptosis;Optic Nerve;Neurites;Rats, Wistar;Not relevant;11 Glia;Animals, Newborn;Support, Non-U.S. Gov't;Neurons;Cerebellum;Mice;Trigeminal Nerve;Microscopy, Electron}, Medline = {99171961}, Month = {2}, Nlm_Id = {8918110}, Number = {2}, Organization = {MGC Department of Clinical Genetics, Institute of Plastic Surgery, Erasmus University Medical School, Rotterdam, The Netherlands. vandeneijnde\@ikg.fgg.eur.nl}, Pages = {712-24}, Pubmed = {10051772}, Title = {Spatiotemporal distribution of dying neurons during early mouse development}, Uuid = {38E772A8-68A5-4B0D-8987-1B89AA882CE0}, Volume = {11}, Year = {1999}, url = {papers/Eijnde_EurJNeurosci1999.pdf}} @article{Pol:2003, Abstract = {Olfactory ensheathing cells (OECs) have considerable potential for facilitating axonal growth across regions of spinal cord and brain injury but in this context have been studied primarily in static images of fixed tissue from the olfactory system or after transplantation. In the present work, we studied the behavior of live OECs, and their interactions with neurons, Schwann cells, and astrocytes by using cells that express the reporter gene coding for green fluorescent protein (GFP); the work is based on combinations of fluorescence, phase contrast, digital time lapse imaging, and P75 immunocytochemical identification. Cultures, explants, and regions of olfactory system slices rich in OECs enhanced axonal growth of cerebellar granule cells or hippocampal neurons; axons grew parallel to the long axis of fusiform OECs. Neuron cell bodies and axons preferred OECs over artificial substrates. Axons and neuron cell bodies can take active or passive roles in extension and migration on underlying motile OECs and move from one OEC to another. Axon extension was facilitated to a similar degree by OECs and Schwann cells, whereas astrocytes were more likely to integrate with existing OECs than with Schwann cells. OECs showed a dramatic ability to rapidly change shape, size, and direction of migration and to undergo mitosis. Mitosis was characterized by a quick retraction of all processes, thereby forming a sphere that divided into spherical daughter cells within minutes. Progeny OECs might take on the parental or a non-parental morphotype, with both daughter cells showing robust expression of GFP. Together these OEC data demonstrated a substantial plasticity and capability for relatively rapid changes in structure and support the view that OECs have multiple attributes favorable for enhancing axonal extension and neuronal migration after central nervous system injury. 0021-9967 Journal Article}, Author = {van den Pol, A. N. and Santarelli, J. G.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Journal = {J Comp Neurol}, Keywords = {Microscopy, Video;Animals;Astrocytes/*cytology;Cell Communication/*physiology;Neurons/*cytology;Neuronal Plasticity/physiology;Mitosis/physiology;Cerebellum/cytology;L pdf;Mice, Transgenic;17 Transplant Regeneration;Olfactory Pathways/*cytology;Cell Division/physiology;Support, U.S. Gov't, P.H.S.;Cell Movement/physiology;Mice;Cell Adhesion/physiology;Organ Culture;Luminescent Proteins/genetics;Indicators and Reagents/metabolism;Schwann Cells/*cytology}, Number = {2}, Organization = {Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA. anthony.vandenpol\@yale.edu}, Pages = {175-94}, Title = {Olfactory ensheathing cells: time lapse imaging of cellular interactions, axonal support, rapid morphologic shifts, and mitosis}, Uuid = {55B1EB8E-0C01-4D3E-95CA-34A50F2DB45C}, Volume = {458}, Year = {2003}, url = {papers/Pol_JCompNeurol2003}} @article{Pol:2002, Abstract = {A new recombinant vesicular stomatitis virus (rVSV) that expresses green fluorescent protein (GFP) on the cytoplasmic domain of the VSV glycoprotein (G protein) was used in the mouse as a model for studying brain infections by a member of the Mononegavirales order that can cause permanent changes in behavior. After nasal administration, virus moved down the olfactory nerve, first to periglomerular cells, then past the mitral cell layer to granule cells, and finally to the subventricular zone. Eight days postinoculation, rVSV was eliminated from the olfactory bulb. Little sign of infection could be found outside the olfactory system, suggesting that anterograde or retrograde axonal transport of rVSV was an unlikely mechanism for movement of rVSV out of the bulb. When administered intracerebrally by microinjection, rVSV spread rapidly within the brain, with strong infection at the site of injection and at some specific periventricular regions of the brain, including the dorsal raphe, locus coeruleus, and midline thalamus; the ventricular system may play a key role in rapid rVSV dispersion within the brain. Thus, the lack of VSV movement out of the olfactory system was not due to the absence of potential for infections in other brain regions. In cultures of both mouse and human central nervous system (CNS) cells, rVSV inoculations resulted in productive infection, expression of the G-GFP fusion protein in the dendritic and somatic plasma membrane, and death of all neurons and glia, as detected by ethidium homodimer nuclear staining. Although considered a neurotropic virus, rVSV also infected heart, skin, and kidney cells in dispersed cultures. rVSV showed a preference for immature neurons in vitro, as shown by enhanced viral infection in developing hippocampal cultures and in the outer granule cell layer in slices of developing cerebellum. Together, these data suggest a relative affinity of rVSV for some neuronal types in the CNS, adding to our understanding of the long-lasting changes in rodent behavior found after transient VSV infection. 0022-538x Journal Article}, Author = {van den Pol, A. N. and Dalton, K. P. and Rose, J. K.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 13:57:02 -0400}, Journal = {J Virol}, Keywords = {Hamsters;Human;Animals;Cells, Cultured;J;Vesicular stomatitis-Indiana virus/genetics/*physiology/ultrastructure;15 Retrovirus mechanism;Neurons/cytology/*virology;Brain/cytology/*virology;Olfactory Bulb/virology;Time Factors;Olfactory Nerve/virology;Cell Line;Administration, Intranasal;Dendrites/virology;Recombination, Genetic;Support, U.S. Gov't, Non-P.H.S.;Support, U.S. Gov't, P.H.S.;Mice;Genes, Reporter;Cell Death;Luminescent Proteins/genetics;Gene Expression;Transgenes}, Number = {3}, Organization = {Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520, USA. anthony.vandenpol\@yale.edu}, Pages = {1309-27}, Pubmed = {11773406}, Title = {Relative neurotropism of a recombinant rhabdovirus expressing a green fluorescent envelope glycoprotein}, Uuid = {46BC1FC4-F857-4510-8E5D-736FFD59F590}, Volume = {76}, Year = {2002}, Bdsk-Url-1 = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11773406}} @article{Gucht:2001, Abstract = {In this immunocytochemical study, we examined the expression profile of neurofilament protein in the cat visual system. We have used SMI-32, a monoclonal antibody that recognizes a nonphosphorylated epitope on the medium- and high-molecular-weight subunits of neurofilament proteins. This antibody labels primarily the cell body and dendrites of pyramidal neurons in cortical layers III, V, and VI. Neurofilament protein-immunoreactive neurons were prominent in 20 visual cortical areas (areas 17, 18, 19, 20a, 20b, 21a, 21b, and 7; posteromedial lateral, posterolateral lateral, anteromedial lateral, anterolateral lateral, dorsal lateral, ventral lateral, and posterior suprasylvian areas; anterior ectosylvian, the splenial, the cingulate, and insular visual areas; and the anterolateral gyrus area). In addition, we have also found strong immunopositive cells in the A laminae of the dorsal part of the lateral geniculate nucleus (dLGN) and in the medial interlaminar nucleus, but no immunoreactive cells were present in the parvocellular C (1-3) laminae of the dLGN, in the ventral part of the LGN and in the perigeniculate nucleus. This SMI-32 antibody against neurofilament protein revealed a characteristic pattern of immunostaining in each visual area. The size, shape, intensity, and density of neurofilament protein-immunoreactive neurons and their dendritic arborization differed substantially across all visual areas. Moreover, it was also obvious that several visual areas showed differences in laminar distribution and that such profiles may be used to delineate various cortical areas. Therefore, the expression of neurofilament protein can be used as a specific marker to define areal patterns and topographic boundaries in the cat visual system.}, Author = {van der Gucht, E. and Vandesande, F. and Arckens, L.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:31 -0400}, Issn = {0021-9967}, Journal = {J Comp Neurol}, Keywords = {Visual Cortex;Cell Size;Visual Perception;Research Support, Non-U.S. Gov't;Dendrites;Cats;Immunohistochemistry;Geniculate Bodies;Antibodies, Monoclonal;Neurofilament Proteins;Pyramidal Cells;Antibody Specificity;Animals;Visual Pathways;23 Technique}, Medline = {21611547}, Month = {12}, Nlm_Id = {0406041}, Number = {4}, Organization = {Laboratory of Neuroendocrinology and Immunological Biotechnology, Katholieke Universiteit Leuven, Naamsestraat 59, B-3000 Leuven, Belgium.}, Pages = {345-68}, Pii = {10.1002/cne.1416}, Pubmed = {11745654}, Title = {Neurofilament protein: a selective marker for the architectonic parcellation of the visual cortex in adult cat brain}, Uuid = {FC814231-D31C-11D9-A0E9-000D9346EC2A}, Volume = {441}, Year = {2001}} @article{Bernhardi:2001, Abstract = {Astrocytes and microglia are closely associated with amyloid plaques in Alzheimer's disease (AD). Microglia constitute the first barrier surrounding plaques, although they seem to be unable to remove them efficiently. We evaluated the reaction of microglial cells from neonatal rats and mice to plaque mimetics. The C-terminal part of the amyloid precursor protein (APP) or amyloid peptide (A beta) was immobilized to either 60-microm or 2.8-microm beads and incubated with microglial cells. Beads of 60 microm, having approximately the size of senile plaques, were not phagocytosed, in contrast to 2.8-microm beads, which were phagocytosed by microglia but not by astrocytes. Once taken up by the cells, proteins immobilized to the beads were degraded rapidly, as confirmed by mass spectrometry and immunofluorescence with an antibody against beta-amyloid. On the other hand, no protein degradation was observed with 60-microm beads. Also, probably as a reaction to its incapability to phagocytose the beads, glia organized around the beads and started to proliferate. Cell proliferation was more pronounced when the beads contained the A beta epitope compared with the beads with an inert surface. This in vitro effect could be exploited to set up a screening assay for compounds that ameliorate the adverse reaction of microglia supposed to contribute to the pathogenesis of AD.}, Author = {von Bernhardi, R. and Ram{\'\i}rez, G. and Matile, H. and D{\"o}beli, H.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:27 -0400}, Issn = {0953-816X}, Journal = {Eur J Neurosci}, Keywords = {Amyloid beta-Protein;Endopeptidases;Indicators and Reagents;Neuroglia;Research Support, Non-U.S. Gov't;Spectrum Analysis, Mass;11 Glia;Amyloid beta-Protein Precursor;Endocytosis;Microspheres;Cells, Cultured;Humans;Cloning, Molecular;Fluorescent Antibody Technique;Nitrites}, Medline = {21479369}, Month = {9}, Nlm_Id = {8918110}, Number = {6}, Organization = {Faculty of Medicine, Universidad de los Andes, San Carlos de Apoquindo 2200, Las Condes, Santiago, Chile. rvonb\@uandes.cl}, Pages = {946-56}, Pii = {ejn1715}, Pubmed = {11595033}, Title = {Immobilized amyloid precursor protein constructs: a tool for the in vitro screening of glial cell reactivity}, Uuid = {783F6750-A63B-4397-8240-BE8700850E37}, Volume = {14}, Year = {2001}} @article{Holst:2006, Abstract = {Neural stem cells have been documented in both the developing and the mature adult CNSs of mammals. This cell population holds a considerable promise for therapeutical applications in a wide array of CNS diseases. Therefore, universally applicable strategies for the purification of this population to further its cell biological characterization are sought. Here, we report that the unique chondroitin sulfate epitope recognized by the monoclonal antibody 473HD is surface expressed on actively cycling, multipotent progenitor cells of the developing telencephalon with radial glia-like properties. When used for immunopanning, the antibody enriched at least threefold for neural stem/progenitor cells characterized by the ability to self-renew as neurospheres that generated all major neural lineages in differentiation assays. In contrast, the 473HD-depleted cell fraction was mostly devoid of neurosphere-forming cells. The isolation of 473HD-positive adult multipotent progenitors from the subependymal zone of the lateral ventricle wall revealed a substantial overlap with the known adult neural stem cell marker LewisX. When the chondroitin sulfates were removed from immunoselected 473HD-positive neural stem/progenitor cell surfaces by chondroitinase ABC treatment or perturbed by the monoclonal antibody 473HD that recognizes the unique DSD-1 chondroitin sulfate epitope, the generation of neurospheres was significantly reduced. Thus, the 473HD epitope could not only be used for the isolation of multipotent neural progenitors during forebrain development as well as from the adult neurogenic niche but may also constitute a functionally important entity of the neural stem cell niche.}, Author = {von Holst, Alexander and Sirko, Swetlana and Faissner, Andreas}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {1529-2401}, Journal = {J Neurosci}, Keywords = {24 Pubmed search results 2008}, Month = {4}, Nlm_Id = {8102140}, Number = {15}, Organization = {Cell Morphology and Molecular Neurobiology, Faculty of Biology, Ruhr-University Bochum, D-44780 Bochum, Germany.}, Pages = {4082-94}, Pii = {26/15/4082}, Pubmed = {16611825}, Title = {The unique 473HD-Chondroitinsulfate epitope is expressed by radial glia and involved in neural precursor cell proliferation}, Uuid = {9447A27D-1611-4392-8C4D-099B1868DCD0}, Volume = {26}, Year = {2006}, Bdsk-Url-1 = {http://dx.doi.org/10.1523/JNEUROSCI.0422-06.2006}} @article{Melchner:2000, Abstract = {An unresolved issue in cortical development concerns the relative contributions of intrinsic and extrinsic factors to the functional specification of different cortical areas. Ferrets in which retinal projections are redirected neonatally to the auditory thalamus have visually responsive cells in auditory thalamus and cortex, form a retinotopic map in auditory cortex and have visual receptive field properties in auditory cortex that are typical of cells in visual cortex. Here we report that this cross-modal projection and its representation in auditory cortex can mediate visual behaviour. When light stimuli are presented in the portion of the visual field that is 'seen' only by this projection, 'rewired' ferrets respond as though they perceive the stimuli to be visual rather than auditory. Thus the perceptual modality of a neocortical region is instructed to a significant extent by its extrinsic inputs. In addition, gratings of different spatial frequencies can be discriminated by the rewired pathway, although the grating acuity is lower than that of the normal visual pathway.}, Author = {von Melchner, L. and Pallas, S. L. and Sur, M.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2011-09-12 11:19:36 -0400}, Issn = {0028-0836}, Journal = {Nature}, Keywords = {Retina;Animals;Photic Stimulation;Ferrets;Visual Perception;Visual Pathways;Denervation;research support, non-u.s. gov't;Vision;Animals, Newborn;Thalamus;research support, u.s. gov't, p.h.s.;21 Neurophysiology;Auditory Pathways;Sound;Auditory Cortex;24 Pubmed search results 2008;Geniculate Bodies}, Month = {4}, Nlm_Id = {0410462}, Number = {6780}, Organization = {Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139, USA.}, Pages = {871-6}, Pubmed = {10786793}, Title = {Visual behaviour mediated by retinal projections directed to the auditory pathway}, Uuid = {A9B72ED0-9057-46AC-AC63-40896F12578B}, Volume = {404}, Year = {2000}, Bdsk-Url-1 = {http://dx.doi.org/10.1038/35009102}} @article{Zahn:1997, Abstract = {Activation of microglial cells in neurological diseases involves proliferation and the induction of phagocytic and cytotoxic properties. We studied the effects of four different cytokines on microglial phagocytosis of latex beads to gain further insights into the signals modulating different aspects of microglial activity. Granulocyte/macrophage colony stimulating factor and tumor necrosis factor-alpha enhanced microglial phagocytic activity as measured by flow cytometry. A phagocytosis inhibiting effect was observed after preincubation with transforming growth factor-beta1 and interleukin-4. In conclusion, the activating and deactivating cytokines differentially regulate microglial phagocytic activity in vitro and might also play an important role in vivo in modulating microglial activation to keep the balance between the protective, defensive and destructive, chronic inflammatory properties of microglia.}, Author = {von Zahn, J. and M{\"o}ller, T. and Kettenmann, H. and Nolte, C.}, Date-Added = {2009-03-25 19:34:04 -0400}, Date-Modified = {2009-03-25 19:55:45 -0400}, Issn = {0959-4965}, Journal = {Neuroreport}, Keywords = {Cells, Cultured;Flow Cytometry;Research Support, Non-U.S. Gov't;Interleukin-4;Cytokines;Inflammation;Granulocyte-Macrophage Colony-Stimulating Factor;Tumor Necrosis Factor-alpha;Microglia;Transforming Growth Factor beta;11 Glia;Microspheres;Mice;Animals;Phagocytosis;Mice, Inbred Strains;Lipopolysaccharides}, Medline = {98122286}, Month = {12}, Nlm_Id = {9100935}, Number = {18}, Organization = {University Hospital Benjamin Franklin, Berlin, Germany.}, Pages = {3851-6}, Pubmed = {9462454}, Title = {Microglial phagocytosis is modulated by pro- and anti-inflammatory cytokines}, Uuid = {908194C7-E3B0-4DBC-9B0A-405906B234E7}, Volume = {8}, Year = {1997}} @article{Smith2017, title = {Cadherin-10 Maintains Excitatory/Inhibitory Ratio through Interactions with Synaptic Proteins.}, author = {Smith, Katharine R and Jones, Kelly A and Kopeikina, Katherine J and Burette, Alain C and Copits, Bryan A and Yoon, Sehyoun and Forrest, Marc P and Fawcett-Patel, Jessica M and Hanley, Jonathan G and Weinberg, Richard J and Swanson, Geoffrey T and Penzes, Peter}, journal = {J Neurosci}, volume = {37}, number = {46}, year = {2017}, month = {Nov}, pages = {11127-11139}, abstract = {Appropriate excitatory/inhibitory (E/I) balance is essential for normal cortical function and is altered in some psychiatric disorders, including autism spectrum disorders (ASDs). Cell-autonomous molecular mechanisms that control the balance of excitatory and inhibitory synapse function remain poorly understood; no proteins that regulate excitatory and inhibitory synapse strength in a coordinated reciprocal manner have been identified. Using super-resolution imaging, electrophysiology, and molecular manipulations, we show that cadherin-10, encoded by CDH10 within the ASD risk locus 5p14.1, maintains both excitatory and inhibitory synaptic scaffold structure in cultured cortical neurons from rats of both sexes. Cadherin-10 localizes to both excitatory and inhibitory synapses in neocortex, where it is organized into nanoscale puncta that influence the size of their associated PSDs. Knockdown of cadherin-10 reduces excitatory but increases inhibitory synapse size and strength, altering the E/I ratio in cortical neurons. Furthermore, cadherin-10 exhibits differential participation in complexes with PSD-95 and gephyrin, which may underlie its role in maintaining the E/I ratio. Our data provide a new mechanism whereby a protein encoded by a common ASD risk factor controls E/I ratios by regulating excitatory and inhibitory synapses in opposing directions.SIGNIFICANCE STATEMENT The correct balance between excitatory/inhibitory (E/I) is crucial for normal brain function and is altered in psychiatric disorders such as autism. However, the molecular mechanisms that underlie this balance remain elusive. To address this, we studied cadherin-10, an adhesion protein that is genetically linked to autism and understudied at the cellular level. Using a combination of advanced microscopy techniques and electrophysiology, we show that cadherin-10 forms nanoscale puncta at excitatory and inhibitory synapses, maintains excitatory and inhibitory synaptic structure, and is essential for maintaining the correct balance between excitation and inhibition in neuronal dendrites. These findings reveal a new mechanism by which E/I balance is controlled in neurons and may bear relevance to synaptic dysfunction in autism.}, keywords = {CDH10; PSD-95; adhesion; cadherin-10; dendritic spines; inhibitory synapses; }, mesh = {Animals; Cadherins; Cells, Cultured; Disks Large Homolog 4 Protein; Excitatory Postsynaptic Potentials; Female; HEK293 Cells; Humans; Inhibitory Postsynaptic Potentials; Male; Mice; Protein Binding; Rats; Rats, Sprague-Dawley; Synapses; }, pmid = {29030434}, pii = {JNEUROSCI.1153-17.2017}, doi = {10.1523/JNEUROSCI.1153-17.2017}, pmc = {PMC5688522}, url = {papers/Smith_JNeurosci2017-29030434.pdf}, nlmuniqueid = {8102140} } @Article{Forrest2018, author = {Forrest, Marc P and Parnell, Euan and Penzes, Peter}, title = {Dendritic structural plasticity and neuropsychiatric disease.}, journal = {Nat Rev Neurosci}, year = {2018}, volume = {19}, number = {4}, pages = {215-234}, month = {Mar}, abstract = {The structure of neuronal circuits that subserve cognitive functions in the brain is shaped and refined throughout development and into adulthood. Evidence from human and animal studies suggests that the cellular and synaptic substrates of these circuits are atypical in neuropsychiatric disorders, indicating that altered structural plasticity may be an important part of the disease biology. Advances in genetics have redefined our understanding of neuropsychiatric disorders and have revealed a spectrum of risk factors that impact pathways known to influence structural plasticity. In this Review, we discuss the importance of recent genetic findings on the different mechanisms of structural plasticity and propose that these converge on shared pathways that can be targeted with novel therapeutics.}, doi = {10.1038/nrn.2018.16}, url = {papers/Forrest_NatRevNeurosci2018-29545546.pdf}, nlmuniqueid = {100962781}, pii = {nrn.2018.16}, pmid = {29545546}} @article{Johnson1981, title = {Neural mechanisms of spatial tactile discrimination: neural patterns evoked by braille-like dot patterns in the monkey.}, author = {Johnson, K O and Lamb, G D}, journal = {J Physiol}, volume = {310}, year = {1981}, month = {Jan}, pages = {117-44}, abstract = {1. The experiments reported here were designed to investigate the responses of cutaneous mechanoreceptive afferents to spatially configured dot patterns scanned across the skin. Braille-like patterns were selected because the discrimination of Braille characters must depend on spatial patterning rather than some other facet of the afferent discharge. 2. A multifactorial experimental design was used in which each afferent fibre was studied using every combination of six dot patterns, two dot sizes, two dot spacings, two contact forces and two scanning velocities. Two other factors, scanning direction relative to the skin ridges and intermittent versus continuous scanning, were studied. 3. Beside the general question concerning the response properties of the mechanoreceptive afferents, three major questions were addressed here. (i) What is the critical spatial dimension at which neural spatial patterning breaks down and below which tactual discrimination must depend on facets of the afferent discharge other than spatial neural patterning? (ii) Which mechanoreceptive population sets this critical dimension? (iii) Why is tactual discrimination enhanced by lateral scanning? 4. The results presented here suggest that the critical dimension, below which spatial neural patterning breaks down, is of the order of 1.0 mm and that the slowly adapting (SA) afferent fibres are responsible for this limit. 5. At dimensions above approximately 1.0 mm the spatial contrast between peaks and troughs in the SA discharge is markedly enhanced during scanning. When the skin is stationary the discharge rates in the SA population drop rapidly to low levels. A second possible reason for enhanced tactual discrimination during scanning is related to the increased spatiotemporal information in a coherent pattern of neural activity moving across a discrete population of afferent fibres. 6. The effects of variations in conduction velocity are analysed and it is shown that they place serious constraints on the transmission of spatiotemporal information.}, pmid = {7230030}, pmc = {PMC1274731}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/7230030}, url = {papers/Johnson_JPhysiol1981-7230030.pdf}, nlmuniqueid = {0266262} } @article{Kaschube2010, title = {Universality in the evolution of orientation columns in the visual cortex.}, author = {Kaschube, Matthias and Schnabel, Michael and Löwel, Siegrid and Coppola, David M and White, Leonard E and Wolf, Fred}, journal = {Science}, volume = {330}, number = {6007}, year = {2010}, month = {Nov}, pages = {1113-6}, abstract = {The brain's visual cortex processes information concerning form, pattern, and motion within functional maps that reflect the layout of neuronal circuits. We analyzed functional maps of orientation preference in the ferret, tree shrew, and galago--three species separated since the basal radiation of placental mammals more than 65 million years ago--and found a common organizing principle. A symmetry-based class of models for the self-organization of cortical networks predicts all essential features of the layout of these neuronal circuits, but only if suppressive long-range interactions dominate development. We show mathematically that orientation-selective long-range connectivity can mediate the required interactions. Our results suggest that self-organization has canalized the evolution of the neuronal circuitry underlying orientation preference maps into a single common design.}, pmid = {21051599}, pii = {science.1194869}, doi = {10.1126/science.1194869}, pmc = {PMC3138194}, mid = {NIHMS302162}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/21051599}, url = {papers/Kaschube_Science2010-21051599.pdf}, nlmuniqueid = {0404511} } @article{Reimann2017, title = {Cliques of Neurons Bound into Cavities Provide a Missing Link between Structure and Function.}, author = {Reimann, Michael W and Nolte, Max and Scolamiero, Martina and Turner, Katharine and Perin, Rodrigo and Chindemi, Giuseppe and Dłotko, Paweł and Levi, Ran and Hess, Kathryn and Markram, Henry}, journal = {Front Comput Neurosci}, volume = {11}, year = {2017}, pages = {48}, abstract = {The lack of a formal link between neural network structure and its emergent function has hampered our understanding of how the brain processes information. We have now come closer to describing such a link by taking the direction of synaptic transmission into account, constructing graphs of a network that reflect the direction of information flow, and analyzing these directed graphs using algebraic topology. Applying this approach to a local network of neurons in the neocortex revealed a remarkably intricate and previously unseen topology of synaptic connectivity. The synaptic network contains an abundance of cliques of neurons bound into cavities that guide the emergence of correlated activity. In response to stimuli, correlated activity binds synaptically connected neurons into functional cliques and cavities that evolve in a stereotypical sequence toward peak complexity. We propose that the brain processes stimuli by forming increasingly complex functional cliques and cavities.}, keywords = {Betti numbers; connectomics; correlations; directed networks; structure-function; topology; }, pmid = {28659782}, doi = {10.3389/fncom.2017.00048}, pmc = {PMC5467434}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/28659782}, url = {}, nlmuniqueid = {101477956} } @article{Fongang2013, title = {The precise timeline of transcriptional regulation reveals causation in mouse somitogenesis network.}, author = {Fongang, Bernard and Kudlicki, Andrzej}, journal = {BMC Dev Biol}, volume = {13}, year = {2013}, month = {Dec}, pages = {42}, abstract = {In vertebrate development, the segmental pattern of the body axis is established as somites, masses of mesoderm distributed along the two sides of the neural tube, are formed sequentially in the anterior-posterior axis. This mechanism depends on waves of gene expression associated with the Notch, Fgf and Wnt pathways. The underlying transcriptional regulation has been studied by whole-transcriptome mRNA profiling; however, interpretation of the results is limited by poor resolution, noisy data, small sample size and by the absence of a wall clock to assign exact time for recorded points.}, pmid = {24304493}, pii = {1471-213X-13-42}, doi = {10.1186/1471-213X-13-42}, pmc = {PMC4235037}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/24304493}, url = {papers/Fongang_BMCDevBiol2013-24304493.pdf}, nlmuniqueid = {100966973} } @article{Dequéant2006, title = {A complex oscillating network of signaling genes underlies the mouse segmentation clock.}, author = {Dequéant, Mary-Lee and Glynn, Earl and Gaudenz, Karin and Wahl, Matthias and Chen, Jie and Mushegian, Arcady and Pourquié, Olivier}, journal = {Science}, volume = {314}, number = {5805}, year = {2006}, month = {Dec}, pages = {1595-8}, abstract = {The segmental pattern of the spine is established early in development, when the vertebral precursors, the somites, are rhythmically produced from the presomitic mesoderm. Microarray studies of the mouse presomitic mesoderm transcriptome reveal that the oscillator associated with this process, the segmentation clock, drives the periodic expression of a large network of cyclic genes involved in cell signaling. Mutually exclusive activation of the notch-fibroblast growth factor and Wnt pathways during each cycle suggests that coordinated regulation of these three pathways underlies the clock oscillator.}, pmid = {17095659}, pii = {1133141}, doi = {10.1126/science.1133141}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/17095659}, url = {papers/Dequéant_Science2006-17095659.pdf}, nlmuniqueid = {0404511} } @article{Aulehla2006, title = {On periodicity and directionality of somitogenesis.}, author = {Aulehla, Alexander and Pourquié, Olivier}, journal = {Anat Embryol (Berl)}, volume = {211 Suppl 1}, year = {2006}, month = {Dec}, pages = {3-8}, abstract = {It is currently thought that the mechanism underlying somitogenesis is linked to a molecular oscillator, the segmentation clock, and to gradients of signaling molecules within the paraxial mesoderm. Here, we review the current picture of this segmentation clock and gradients, and use this knowledge to critically ask: What is the basis for periodicity and directionality of somitogenesis?}, pmid = {17024300}, doi = {10.1007/s00429-006-0124-y}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/17024300}, url = {papers/Aulehla_AnatEmbryol(Berl)2006-17024300.pdf}, nlmuniqueid = {7505194} } @article{Pittendrigh1954, title = {ON TEMPERATURE INDEPENDENCE IN THE CLOCK SYSTEM CONTROLLING EMERGENCE TIME IN DROSOPHILA.}, author = {Pittendrigh, C S}, journal = {Proc Natl Acad Sci U S A}, volume = {40}, number = {10}, year = {1954}, month = {Oct}, pages = {1018-29}, pmid = {16589583}, pmc = {PMC534216}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/16589583}, url = {papers/Pittendrigh_ProcNatlAcadSciUSA1954-16589583.pdf}, nlmuniqueid = {7505876} } @article{Mizuno2018, title = {Patchwork-Type Spontaneous Activity in Neonatal Barrel Cortex Layer 4 Transmitted via Thalamocortical Projections.}, author = {Mizuno, Hidenobu and Ikezoe, Koji and Nakazawa, Shingo and Sato, Takuya and Kitamura, Kazuo and Iwasato, Takuji}, journal = {Cell Rep}, volume = {22}, number = {1}, year = {2018}, month = {Jan}, pages = {123-135}, abstract = {Establishment of precise neuronal connectivity in the neocortex relies on activity-dependent circuit reorganization during postnatal development; however, the nature of cortical activity during this period remains largely unknown. Using two-photon calcium imaging of the barrel cortex in vivo during the first postnatal week, we reveal that layer 4 (L4) neurons within the same barrel fire synchronously in the absence of peripheral stimulation, creating a "patchwork" pattern of spontaneous activity corresponding to the barrel map. By generating transgenic mice expressing GCaMP6s in thalamocortical axons, we show that thalamocortical axons also demonstrate the spontaneous patchwork activity pattern. Patchwork activity is diminished by peripheral anesthesia but is mostly independent of self-generated whisker movements. The patchwork activity pattern largely disappeared during postnatal week 2, as even L4 neurons within the same barrel tended to fire asynchronously. This spontaneous L4 activity pattern has features suitable for thalamocortical (TC) circuit refinement in the neonatal barrel cortex.}, keywords = {activity-dependent development; awake; barrel cortex; in vivo calcium imaging; neonates; single-cell labeling; spontaneous activity; synchronized activity; thalamocortical axons; whisker monitoring; }, pmid = {29298415}, pii = {S2211-1247(17)31808-9}, doi = {10.1016/j.celrep.2017.12.012}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/29298415}, url = {papers/Mizuno_CellRep2018-29298415.pdf}, nlmuniqueid = {101573691} } @article{Petersen2007, title = {The functional organization of the barrel cortex.}, author = {Petersen, Carl C H}, journal = {Neuron}, volume = {56}, number = {2}, year = {2007}, month = {Oct}, pages = {339-55}, abstract = {The tactile somatosensory pathway from whisker to cortex in rodents provides a well-defined system for exploring the link between molecular mechanisms, synaptic circuits, and behavior. The primary somatosensory cortex has an exquisite somatotopic map where each individual whisker is represented in a discrete anatomical unit, the "barrel," allowing precise delineation of functional organization, development, and plasticity. Sensory information is actively acquired in awake behaving rodents and processed differently within the barrel map depending upon whisker-related behavior. The prominence of state-dependent cortical sensory processing is likely to be crucial in our understanding of active sensory perception, experience-dependent plasticity and learning.}, pmid = {17964250}, pii = {S0896-6273(07)00715-5}, doi = {10.1016/j.neuron.2007.09.017}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/17964250}, url = {papers/Petersen_Neuron2007-17964250.pdf}, nlmuniqueid = {8809320} } @article{Vanni2014, title = {Mesoscale transcranial spontaneous activity mapping in GCaMP3 transgenic mice reveals extensive reciprocal connections between areas of somatomotor cortex.}, author = {Vanni, Matthieu P and Murphy, Timothy H}, journal = {J Neurosci}, volume = {34}, number = {48}, year = {2014}, month = {Nov}, pages = {15931-46}, abstract = {Transgenic mice expressing genetically encoded activity indicators are an attractive means of mapping mesoscopic regional functional cortical connectivity given widespread stable and cell-specific expression compatible with chronic recordings. Cortical functional connectivity was evaluated using wide-field imaging in lightly anesthetized Emx1-creXRosa26-GCaMP3 mice expressing calcium sensor in cortical neurons. Challenges exist because green fluorescence signals overlap with endogenous activity-dependent autofluorescence and are affected by changes in blood volume and oxygenation. Under the conditions used for imaging and analysis (0.1-1 Hz frequency band), autofluorescence and hemodynamic effects contributed 3% and 8% of the SD of spontaneous activity-dependent GCaMP3 fluorescence when signals were recorded through intact bone. To evaluate the accuracy and sensitivity of this approach, the topology of functional connections between somatomotor cortex (primary S1 and secondary S2 somatosensory, and primary motor cortex M1) was estimated. During sequences of spontaneous activity, calcium signals recorded at each location of area S1 were correlated with activity in contralateral area S1, ipsilateral area S2, and bilateral areas M1. Reciprocal results were observed when "seed pixels" were placed in S2 and M1. Coactivation of areas implies functional connections but could also be attributed to both regions receiving common upstream drive. These apparent connections revealed during spontaneous activity coactivation by GCaMP3 were confirmed by intracortical microstimulation but were more difficult to detect using intrinsic signals from reflected red light. We anticipate GCAMP wide-field imaging will enable longitudinal studies during plasticity paradigms or after models of CNS disease, such as stroke, where the weighting within these connectivity maps may be altered. }, keywords = {connectome; cortical stimulation; optogenetic; resting state; tracing; transgenic mice; Animals; Brain Mapping; Calcium Signaling; Female; Male; Mice; Mice, 129 Strain; Mice, Transgenic; Motor Cortex; Neural Pathways; Somatosensory Cortex; }, pmid = {25429135}, pii = {34/48/15931}, doi = {10.1523/JNEUROSCI.1818-14.2014}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/25429135}, url = {papers/Vanni_JNeurosci2014-25429135.pdf}, nlmuniqueid = {8102140} } @article{Waters2019, title = {Biological variation in the sizes, shapes and locations of visual cortical areas in the mouse.}, author = {Waters, Jack and Lee, Eric and Gaudreault, Nathalie and Griffin, Fiona and Lecoq, Jerome and Slaughterbeck, Cliff and Sullivan, David and Farrell, Colin and Perkins, Jed and Reid, David and Feng, David and Graddis, Nile and Garrett, Marina and Li, Yang and Long, Fuhui and Mochizuki, Chris and Roll, Kate and Zhuang, Jun and Thompson, Carol}, journal = {PLoS One}, volume = {14}, number = {5}, year = {2019}, pages = {e0213924}, abstract = {Visual cortex is organized into discrete sub-regions or areas that are arranged into a hierarchy and serves different functions in the processing of visual information. In retinotopic maps of mouse cortex, there appear to be substantial mouse-to-mouse differences in visual area location, size and shape. Here we quantify the biological variation in the size, shape and locations of 11 visual areas in the mouse, after separating biological variation and measurement noise. We find that there is biological variation in the locations and sizes of visual areas.}, pmid = {31042712}, doi = {10.1371/journal.pone.0213924}, pii = {PONE-D-18-29482}, pmc = {PMC6493719}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/31042712}, url = {}, nlmuniqueid = {101285081} } @article{Ghanbari2019, title = {Cortex-wide neural interfacing via transparent polymer skulls.}, author = {Ghanbari, Leila and Carter, Russell E and Rynes, Mathew L and Dominguez, Judith and Chen, Gang and Naik, Anant and Hu, Jia and Sagar, Md Abdul Kader and Haltom, Lenora and Mossazghi, Nahom and Gray, Madelyn M and West, Sarah L and Eliceiri, Kevin W and Ebner, Timothy J and Kodandaramaiah, Suhasa B}, journal = {Nat Commun}, volume = {10}, number = {1}, year = {2019}, month = {04}, pages = {1500}, abstract = {Neural computations occurring simultaneously in multiple cerebral cortical regions are critical for mediating behaviors. Progress has been made in understanding how neural activity in specific cortical regions contributes to behavior. However, there is a lack of tools that allow simultaneous monitoring and perturbing neural activity from multiple cortical regions. We engineered 'See-Shells'-digitally designed, morphologically realistic, transparent polymer skulls that allow long-term (>300 days) optical access to 45 mm2 of the dorsal cerebral cortex in the mouse. We demonstrate the ability to perform mesoscopic imaging, as well as cellular and subcellular resolution two-photon imaging of neural structures up to 600 µm deep. See-Shells allow calcium imaging from multiple, non-contiguous regions across the cortex. Perforated See-Shells enable introducing penetrating neural probes to perturb or record neural activity simultaneously with whole cortex imaging. See-Shells are constructed using common desktop fabrication tools, providing a powerful tool for investigating brain structure and function.}, pmid = {30940809}, doi = {10.1038/s41467-019-09488-0}, pii = {10.1038/s41467-019-09488-0}, pmc = {PMC6445105}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/30940809}, url = {papers/Ghanbari_NatCommun2019-30940809.pdf}, nlmuniqueid = {101528555} } @article{Scott2016, title = {Longitudinal analysis of the developing rhesus monkey brain using magnetic resonance imaging: birth to adulthood.}, author = {Scott, Julia A and Grayson, David and Fletcher, Evan and Lee, Aaron and Bauman, Melissa D and Schumann, Cynthia Mills and Buonocore, Michael H and Amaral, David G}, journal = {Brain Struct Funct}, volume = {221}, number = {5}, year = {2016}, month = {06}, pages = {2847-71}, abstract = {We have longitudinally assessed normative brain growth patterns in naturalistically reared Macaca mulatta monkeys. Postnatal to early adulthood brain development in two cohorts of rhesus monkeys was analyzed using magnetic resonance imaging. Cohort A consisted of 24 rhesus monkeys (12 male, 12 female) and cohort B of 21 monkeys (11 male, 10 female). All subjects were scanned at 1, 4, 8, 13, 26, 39, and 52 weeks; cohort A had additional scans at 156 weeks (3 years) and 260 weeks (5 years). Age-specific segmentation templates were developed for automated volumetric analyses of the T1-weighted magnetic resonance imaging scans. Trajectories of total brain size as well as cerebral and subcortical subdivisions were evaluated over this period. Total brain volume was about 64 % of adult estimates in the 1-week-old monkey. Brain volume of the male subjects was always, on average, larger than the female subjects. While brain volume generally increased between any two imaging time points, there was a transient plateau of brain growth between 26 and 39 weeks in both cohorts of monkeys. The trajectory of enlargement differed across cortical regions with the occipital cortex demonstrating the most idiosyncratic pattern of maturation and the frontal and temporal lobes showing the greatest and most protracted growth. A variety of allometric measurements were also acquired and body weight gain was most closely associated with the rate of brain growth. These findings provide a valuable baseline for the effects of fetal and early postnatal manipulations on the pattern of abnormal brain growth related to neurodevelopmental disorders.}, keywords = {Allometry; Development; Macaca mulatta; Nonhuman primate; Sexual dimorphism; Animals; Brain; Female; Functional Laterality; Image Processing, Computer-Assisted; Longitudinal Studies; Macaca mulatta; Magnetic Resonance Imaging; Male; }, pmid = {26159774}, doi = {10.1007/s00429-015-1076-x}, pii = {10.1007/s00429-015-1076-x}, pmc = {PMC4884209}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/26159774}, url = {papers/Scott_BrainStructFunct2016-26159774.pdf}, nlmuniqueid = {101282001} } @article{Xiao2017, title = {Mapping cortical mesoscopic networks of single spiking cortical or sub-cortical neurons.}, author = {Xiao, Dongsheng and Vanni, Matthieu P and Mitelut, Catalin C and Chan, Allen W and LeDue, Jeffrey M and Xie, Yicheng and Chen, Andrew Cn and Swindale, Nicholas V and Murphy, Timothy H}, journal = {Elife}, volume = {6}, year = {2017}, month = {02}, pages = {}, abstract = {Understanding the basis of brain function requires knowledge of cortical operations over wide-spatial scales, but also within the context of single neurons. In vivo, wide-field GCaMP imaging and sub-cortical/cortical cellular electrophysiology were used in mice to investigate relationships between spontaneous single neuron spiking and mesoscopic cortical activity. We make use of a rich set of cortical activity motifs that are present in spontaneous activity in anesthetized and awake animals. A mesoscale spike-triggered averaging procedure allowed the identification of motifs that are preferentially linked to individual spiking neurons by employing genetically targeted indicators of neuronal activity. Thalamic neurons predicted and reported specific cycles of wide-scale cortical inhibition/excitation. In contrast, spike-triggered maps derived from single cortical neurons yielded spatio-temporal maps expected for regional cortical consensus function. This approach can define network relationships between any point source of neuronal spiking and mesoscale cortical maps.}, keywords = {functional connectivity; mesoscale maps; mouse; neuroscience; spike triggered maps; thalamocortical; Action Potentials; Anesthesia; Animals; Brain Mapping; Calcium; Calcium Signaling; Cerebral Cortex; Electrodes, Implanted; Male; Mice; Mice, Transgenic; Molecular Probes; Nerve Net; Neurons; Optical Imaging; Stereotaxic Techniques; Thalamus; Wakefulness; }, pmid = {28160463}, doi = {10.7554/eLife.19976}, pmc = {PMC5328594}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/28160463}, url = {papers/Xiao_Elife2017-28160463.pdf}, nlmuniqueid = {101579614} } @article {Barson2018, author = {Barson, D and Hamodi, AS and Shen, X and Lur, G and Constable, RT and Cardin, JA and Crair, MC and Higley, MJ}, title = {Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits}, elocation-id = {468348}, year = {2018}, doi = {10.1101/468348}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Spontaneous and sensory-evoked activity propagates across spatial scales in the mammalian cortex but technical challenges have generally precluded establishing conceptual links between the function of local circuits of neurons and brain-wide network dynamics. To solve this problem, we developed a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake, behaving mice. Our method employs an orthogonal axis design whereby the mesoscopic objective is oriented downward directly above the brain and the two-photon objective is oriented horizontally, with imaging performed through a glass right angle microprism implanted in the skull. In support of this method, we introduce a suite of analysis tools for relating the activity of individual cells to distal cortical areas, as well as a viral method for robust and widespread gene delivery in the juvenile mouse brain. We use these methods to characterize the diversity of associations of individual, genetically-defined neurons with cortex-wide network motifs.}, eprint = {https://www.biorxiv.org/content/early/2018/11/11/468348.full.pdf}, journal = {bioRxiv} } @article{Manita2015, title = {A Top-Down Cortical Circuit for Accurate Sensory Perception.}, author = {Manita, Satoshi and Suzuki, Takayuki and Homma, Chihiro and Matsumoto, Takashi and Odagawa, Maya and Yamada, Kazuyuki and Ota, Keisuke and Matsubara, Chie and Inutsuka, Ayumu and Sato, Masaaki and Ohkura, Masamichi and Yamanaka, Akihiro and Yanagawa, Yuchio and Nakai, Junichi and Hayashi, Yasunori and Larkum, Matthew E and Murayama, Masanori}, journal = {Neuron}, volume = {86}, number = {5}, year = {2015}, month = {Jun}, pages = {1304-16}, abstract = {A fundamental issue in cortical processing of sensory information is whether top-down control circuits from higher brain areas to primary sensory areas not only modulate but actively engage in perception. Here, we report the identification of a neural circuit for top-down control in the mouse somatosensory system. The circuit consisted of a long-range reciprocal projection between M2 secondary motor cortex and S1 primary somatosensory cortex. In vivo physiological recordings revealed that sensory stimulation induced sequential S1 to M2 followed by M2 to S1 neural activity. The top-down projection from M2 to S1 initiated dendritic spikes and persistent firing of S1 layer 5 (L5) neurons. Optogenetic inhibition of M2 input to S1 decreased L5 firing and the accurate perception of tactile surfaces. These findings demonstrate that recurrent input to sensory areas is essential for accurate perception and provide a physiological model for one type of top-down control circuit. }, pmid = {26004915}, pii = {S0896-6273(15)00413-4}, doi = {10.1016/j.neuron.2015.05.006}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/26004915}, url = {papers/Manita_Neuron2015-26004915.pdf}, nlmuniqueid = {8809320} } @article{Heiligenberg1991, title = {The neural basis of behavior: a neuroethological view.}, author = {Heiligenberg, W}, journal = {Annu Rev Neurosci}, volume = {14}, year = {1991}, pages = {247-67}, pmid = {2031571}, doi = {10.1146/annurev.ne.14.030191.001335}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/2031571}, url = {papers/Heiligenberg_AnnuRevNeurosci1991-2031571.pdf}, nlmuniqueid = {7804039} } @article{Doucet2019, title = {Abnormal auditory tonotopy in patients with schizophrenia.}, author = {Doucet, Gaelle E and Luber, Maxwell J and Balchandani, Priti and Sommer, Iris E and Frangou, Sophia}, journal = {NPJ Schizophr}, volume = {5}, number = {1}, year = {2019}, month = {Oct}, pages = {16}, abstract = {Auditory hallucinations are among the most prevalent and most distressing symptoms of schizophrenia. Despite significant progress, it is still unclear whether auditory hallucinations arise from abnormalities in primary sensory processing or whether they represent failures of higher-order functions. To address this knowledge gap, we capitalized on the increased spatial resolution afforded by ultra-high field imaging at 7 Tesla to investigate the tonotopic organization of the auditory cortex in patients with schizophrenia with a history of recurrent hallucinations. Tonotopy is a fundamental feature of the functional organization of the auditory cortex that is established very early in development and predates the onset of symptoms by decades. Compared to healthy participants, patients showed abnormally increased activation and altered tonotopic organization of the auditory cortex during a purely perceptual task, which involved passive listening to tones across a range of frequencies (88-8000 Hz). These findings suggest that the predisposition to auditory hallucinations is likely to be predicated on abnormalities in the functional organization of the auditory cortex and which may serve as a biomarker for the early identification of vulnerable individuals.}, pmid = {31578332}, doi = {10.1038/s41537-019-0084-x}, pii = {10.1038/s41537-019-0084-x}, pmc = {PMC6775081}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/31578332}, url = {papers/Doucet_NPJSchizophr2019-31578332.pdf}, nlmuniqueid = {101657919} } @article{Rudy2011, title = {Three groups of interneurons account for nearly 100% of neocortical GABAergic neurons.}, author = {Rudy, Bernardo and Fishell, Gordon and Lee, SooHyun and Hjerling-Leffler, Jens}, journal = {Dev Neurobiol}, volume = {71}, number = {1}, year = {2011}, month = {Jan}, pages = {45-61}, abstract = {An understanding of the diversity of cortical GABAergic interneurons is critical to understand the function of the cerebral cortex. Recent data suggest that neurons expressing three markers, the Ca2+-binding protein parvalbumin (PV), the neuropeptide somatostatin (SST), and the ionotropic serotonin receptor 5HT3a (5HT3aR) account for nearly 100% of neocortical interneurons. Interneurons expressing each of these markers have a different embryological origin. Each group includes several types of interneurons that differ in morphological and electrophysiological properties and likely have different functions in the cortical circuit. The PV group accounts for ∼40% of GABAergic neurons and includes fast spiking basket cells and chandelier cells. The SST group, which represents ∼30% of GABAergic neurons, includes the Martinotti cells and a set of neurons that specifically target layerIV. The 5HT3aR group, which also accounts for ∼30% of the total interneuronal population, is heterogeneous and includes all of the neurons that express the neuropeptide VIP, as well as an equally numerous subgroup of neurons that do not express VIP and includes neurogliaform cells. The universal modulation of these neurons by serotonin and acetylcholine via ionotropic receptors suggests that they might be involved in shaping cortical circuits during specific brain states and behavioral contexts.}, pmid = {21154909}, doi = {10.1002/dneu.20853}, pmc = {PMC3556905}, mid = {NIHMS434044}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/21154909}, url = {papers/Rudy_DevNeurobiol2011-21154909.pdf}, nlmuniqueid = {101300215} } @article{Athilingam2017, title = {Serotonin enhances excitability and gamma frequency temporal integration in mouse prefrontal fast-spiking interneurons.}, author = {Athilingam, Jegath C and Ben-Shalom, Roy and Keeshen, Caroline M and Sohal, Vikaas S and Bender, Kevin J}, journal = {Elife}, volume = {6}, year = {2017}, month = {12}, pages = {}, abstract = {The medial prefrontal cortex plays a key role in higher order cognitive functions like decision making and social cognition. These complex behaviors emerge from the coordinated firing of prefrontal neurons. Fast-spiking interneurons (FSIs) control the timing of excitatory neuron firing via somatic inhibition and generate gamma (30-100 Hz) oscillations. Therefore, factors that regulate how FSIs respond to gamma-frequency input could affect both prefrontal circuit activity and behavior. Here, we show that serotonin (5HT), which is known to regulate gamma power, acts via 5HT2A receptors to suppress an inward-rectifying potassium conductance in FSIs. This leads to depolarization, increased input resistance, enhanced spiking, and slowed decay of excitatory post-synaptic potentials (EPSPs). Notably, we found that slowed EPSP decay preferentially enhanced temporal summation and firing elicited by gamma frequency inputs. These findings show how changes in passive membrane properties can affect not only neuronal excitability but also the temporal filtering of synaptic inputs.}, keywords = {fast-spiking interneurons; mouse; neuroscience; parvalbumin interneurons; prefrontal cortex; serotonin; synaptic integration; temporal summation; Action Potentials; Animals; Electric Conductivity; Gamma Rhythm; Interneurons; Mice; Models, Neurological; Optical Imaging; Potassium Channels; Prefrontal Cortex; Receptors, Serotonin; Serotonin; }, pmid = {29206101}, doi = {10.7554/eLife.31991}, pmc = {PMC5746342}, pii = {31991}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/29206101}, url = {}, nlmuniqueid = {101579614} } @article{Weber2010, title = {Htr2a Gene and 5-HT(2A) Receptor Expression in the Cerebral Cortex Studied Using Genetically Modified Mice.}, author = {Weber, Elaine T and Andrade, Rodrigo}, journal = {Front Neurosci}, volume = {4}, year = {2010}, pages = {}, abstract = {Serotonin receptors of the 5-HT(2A) subtype are robustly expressed in the cerebral cortex where they have been implicated in the pathophysiology and therapeutics of mental disorders and the actions of hallucinogens. Much less is known, however, about the specific cell types expressing 5-HT(2A) receptors in cortex. In the current study we use immunohistochemical and electrophysiological approaches in genetically modified mice to address the expression of the Htr2a gene and 5-HT(2A) receptors in cortex. We first use an EGFP-expressing BAC transgenic mice and identify three main Htr2A gene expressing neuronal populations in cortex. The largest of these cell populations corresponds to layer V pyramidal cells of the anterior cortex, followed by GABAergic interneurons of the middle layers, and non-pyramidal cells of the subplate/Layer VIb. We then use 5-HT(2A) receptor knockout mice to identify an antibody capable of localizing 5-HT(2A) receptors in brain and use it to map these receptors. We find strong laminar expression of 5-HT(2A) receptors in cortex, especially along a diffuse band overlaying layer Va. This band exhibits a strong anteroposterior gradient that closely matches the localization of Htr2A expressing pyramidal cells of layer V. Finally we use electrophysiological and immunohistochemical approaches to show that most, but not all, GABAergic interneurons of the middle layers are parvalbumin expressing Fast-spiking interneurons and that these cells are depolarized and excited by serotonin, most likely through the activation of 5-HT(2A) receptors. These results clarify and extend our understanding of the cellular distribution of 5-HT(2A) receptors in the cerebral cortex.}, keywords = {5-HT2A; cortex; interneuron; prefrontal; pyramidal cell; serotonin; serotonin receptors; }, pmid = {20802802}, doi = {10.3389/fnins.2010.00036}, pmc = {PMC2928707}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/20802802}, url = {}, nlmuniqueid = {101478481} } @article{Nichols2016, title = {Psychedelics.}, author = {Nichols, David E}, journal = {Pharmacol Rev}, volume = {68}, number = {2}, year = {2016}, month = {Apr}, pages = {264-355}, abstract = {Psychedelics (serotonergic hallucinogens) are powerful psychoactive substances that alter perception and mood and affect numerous cognitive processes. They are generally considered physiologically safe and do not lead to dependence or addiction. Their origin predates written history, and they were employed by early cultures in many sociocultural and ritual contexts. After the virtually contemporaneous discovery of (5R,8R)-(+)-lysergic acid-N,N-diethylamide (LSD)-25 and the identification of serotonin in the brain, early research focused intensively on the possibility that LSD and other psychedelics had a serotonergic basis for their action. Today there is a consensus that psychedelics are agonists or partial agonists at brain serotonin 5-hydroxytryptamine 2A receptors, with particular importance on those expressed on apical dendrites of neocortical pyramidal cells in layer V. Several useful rodent models have been developed over the years to help unravel the neurochemical correlates of serotonin 5-hydroxytryptamine 2A receptor activation in the brain, and a variety of imaging techniques have been employed to identify key brain areas that are directly affected by psychedelics. Recent and exciting developments in the field have occurred in clinical research, where several double-blind placebo-controlled phase 2 studies of psilocybin-assisted psychotherapy in patients with cancer-related psychosocial distress have demonstrated unprecedented positive relief of anxiety and depression. Two small pilot studies of psilocybin-assisted psychotherapy also have shown positive benefit in treating both alcohol and nicotine addiction. Recently, blood oxygen level-dependent functional magnetic resonance imaging and magnetoencephalography have been employed for in vivo brain imaging in humans after administration of a psychedelic, and results indicate that intravenously administered psilocybin and LSD produce decreases in oscillatory power in areas of the brain's default mode network. }, pmid = {26841800}, pii = {68/2/264}, doi = {10.1124/pr.115.011478}, pmc = {PMC4813425}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/26841800}, url = {papers/Nichols_PharmacolRev2016-26841800.pdf}, nlmuniqueid = {0421737} } @article{Kvam2018, title = {Psychedelic drugs in the treatment of anxiety, depression and addiction.}, author = {Kvam, Tor-Morten and Stewart, Lowan H and Andreassen, Ole A}, journal = {Tidsskr Nor Laegeforen}, volume = {138}, number = {18}, year = {2018}, month = {11}, pages = {}, abstract = {Det er økt interesse for psykedeliske stoffer til bruk i behandling av psykiske lidelser. Stoffene regnes som trygge når de gis innenfor en klinisk ramme. Eldre studier fra før 1970 har metodologiske svakheter, men i de senere år har det kommet lovende resultater fra bruk ved unipolar depresjon, depresjon ved livstruende sykdom, angst og avhengighet. Formålet med denne litteraturgjennomgangen er å gi en oversikt over nyere resultater og disse studienes begrensninger.}, pmid = {30421744}, pii = {17-1110}, doi = {10.4045/tidsskr.17.1110}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/30421744}, url = {papers/Kvam_TidsskrNorLaegeforen2018-30421744.pdf}, nlmuniqueid = {0413423} } @article{Carhart-Harris2014, title = {The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.}, author = {Carhart-Harris, Robin L and Leech, Robert and Hellyer, Peter J and Shanahan, Murray and Feilding, Amanda and Tagliazucchi, Enzo and Chialvo, Dante R and Nutt, David}, journal = {Front Hum Neurosci}, volume = {8}, year = {2014}, pages = {20}, abstract = {Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of "primary states" is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit "criticality," i.e., the property of being poised at a "critical" point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetized state. }, keywords = {5-HT2A receptor; REM sleep; consciousness; criticality; default mode network; entropy; metastability; serotonin; }, pmid = {24550805}, doi = {10.3389/fnhum.2014.00020}, pmc = {PMC3909994}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/24550805}, url = {papers/Carhart-Harris_FrontHumNeurosci2014-24550805.pdf}, nlmuniqueid = {101477954} } @article{Tononi1994, title = {A measure for brain complexity: relating functional segregation and integration in the nervous system.}, author = {Tononi, G and Sporns, O and Edelman, G M}, journal = {Proc Natl Acad Sci U S A}, volume = {91}, number = {11}, year = {1994}, month = {May}, pages = {5033-7}, abstract = {In brains of higher vertebrates, the functional segregation of local areas that differ in their anatomy and physiology contrasts sharply with their global integration during perception and behavior. In this paper, we introduce a measure, called neural complexity (CN), that captures the interplay between these two fundamental aspects of brain organization. We express functional segregation within a neural system in terms of the relative statistical independence of small subsets of the system and functional integration in terms of significant deviations from independence of large subsets. CN is then obtained from estimates of the average deviation from statistical independence for subsets of increasing size. CN is shown to be high when functional segregation coexists with integration and to be low when the components of a system are either completely independent (segregated) or completely dependent (integrated). We apply this complexity measure in computer simulations of cortical areas to examine how some basic principles of neuroanatomical organization constrain brain dynamics. We show that the connectivity patterns of the cerebral cortex, such as a high density of connections, strong local connectivity organizing cells into neuronal groups, patchiness in the connectivity among neuronal groups, and prevalent reciprocal connections, are associated with high values of CN. The approach outlined here may prove useful in analyzing complexity in other biological domains such as gene regulation and embryogenesis.}, pmid = {8197179}, pmc = {PMC43925}, doi = {10.1073/pnas.91.11.5033}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/8197179}, url = {papers/Tononi_ProcNatlAcadSciUSA1994-8197179.pdf}, nlmuniqueid = {7505876} } @article{Ly2018, title = {Psychedelics Promote Structural and Functional Neural Plasticity.}, author = {Ly, Calvin and Greb, Alexandra C and Cameron, Lindsay P and Wong, Jonathan M and Barragan, Eden V and Wilson, Paige C and Burbach, Kyle F and Soltanzadeh Zarandi, Sina and Sood, Alexander and Paddy, Michael R and Duim, Whitney C and Dennis, Megan Y and McAllister, A Kimberley and Ori-McKenney, Kassandra M and Gray, John A and Olson, David E}, journal = {Cell Rep}, volume = {23}, number = {11}, year = {2018}, month = {06}, pages = {3170-3182}, abstract = {Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders.}, keywords = {DMT; LSD; MDMA; depression; ketamine; neural plasticity; noribogaine; psychedelic; spinogenesis; synaptogenesis; Animals; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Cells, Cultured; Cerebral Cortex; Female; Male; Microscopy, Fluorescence; Neurogenesis; Neuronal Plasticity; Rats; Rats, Sprague-Dawley; Receptor, Serotonin, 5-HT2A; Receptor, trkB; Signal Transduction; TOR Serine-Threonine Kinases; }, pmid = {29898390}, pii = {S2211-1247(18)30755-1}, doi = {10.1016/j.celrep.2018.05.022}, pmc = {PMC6082376}, mid = {NIHMS977843}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/29898390}, url = {papers/Ly_CellRep2018-29898390.pdf}, nlmuniqueid = {101573691} } @article{Wasko2018, title = {DARK Classics in Chemical Neuroscience: Ibogaine.}, author = {Wasko, Michael J and Witt-Enderby, Paula A and Surratt, Christopher K}, journal = {ACS Chem Neurosci}, volume = {9}, number = {10}, year = {2018}, month = {10}, pages = {2475-2483}, abstract = {The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga's psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a wide spectrum of receptor and transporter proteins; recent work suggests that its actions at nicotinic acetylcholine receptor subtypes may underlie its reputed antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic and has been linked to several deaths by cardiac arrest. Structure-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogaine's anticraving properties with few or no adverse effects. Clinical trials of 18-MC treatment of nicotine addiction are pending. Ibogaine analogs may also hold promise for treating anxiety and depression via the "psychedelic-assisted therapy" approach that employs hallucinogens including psilocybin and methylenedioxymethamphetamine ("ecstasy").}, keywords = {addiction; hallucinogen; iboga; nicotine; opioid; therapeutic; Cardiotoxicity; Hallucinogens; History, 20th Century; History, 21st Century; Humans; Ibogaine; Receptors, Nicotinic; Structure-Activity Relationship; Substance-Related Disorders; Tabernaemontana; }, pmid = {30216039}, doi = {10.1021/acschemneuro.8b00294}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/30216039}, url = {papers/Wasko_ACSChemNeurosci2018-30216039.pdf}, nlmuniqueid = {101525337} } @article{Alper2012, title = {Fatalities temporally associated with the ingestion of ibogaine.}, author = {Alper, Kenneth R and Stajić, Marina and Gill, James R}, journal = {J Forensic Sci}, volume = {57}, number = {2}, year = {2012}, month = {Mar}, pages = {398-412}, abstract = {Ibogaine is a naturally occurring psychoactive plant alkaloid that is used globally in medical and nonmedical settings for opioid detoxification and other substance use indications. All available autopsy, toxicological, and investigative reports were systematically reviewed for the consecutive series of all known fatalities outside of West Central Africa temporally related to the use of ibogaine from 1990 through 2008. Nineteen individuals (15 men, four women between 24 and 54 years old) are known to have died within 1.5-76 h of taking ibogaine. The clinical and postmortem evidence did not suggest a characteristic syndrome of neurotoxicity. Advanced preexisting medical comorbidities, which were mainly cardiovascular, and/or one or more commonly abused substances explained or contributed to the death in 12 of the 14 cases for which adequate postmortem data were available. Other apparent risk factors include seizures associated with withdrawal from alcohol and benzodiazepines and the uninformed use of ethnopharmacological forms of ibogaine.}, pmid = {22268458}, doi = {10.1111/j.1556-4029.2011.02008.x}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/22268458}, url = {papers/Alper_JForensicSci2012-22268458.pdf}, nlmuniqueid = {0375370} } @article{Raouf2017, title = {Serotonin-norepinephrine reuptake inhibitors and the influence of binding affinity (Ki) on analgesia.}, author = {Raouf, M and Glogowski, A J and Bettinger, J J and Fudin, J}, journal = {J Clin Pharm Ther}, volume = {42}, number = {4}, year = {2017}, month = {Aug}, pages = {513-517}, abstract = {Serotonin-norepinephrine reuptake inhibitors (SNRIs) are commonly used for various psychiatric conditions and neuropathic pain syndromes. SNRIs inhibit the reuptake of serotonin (5-HT) and norepinephrine (NE); however, NE reuptake inhibition is thought to be the primary mediator for their analgesic effect.}, keywords = {antidepressants; binding affinity; neuropathic pain; pain; serotonin-norepinephrine reuptake inhibitors; Analgesics; Dose-Response Relationship, Drug; Humans; Neuralgia; Norepinephrine; Serotonin; Serotonin and Noradrenaline Reuptake Inhibitors; }, pmid = {28503727}, doi = {10.1111/jcpt.12534}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/28503727}, url = {papers/Raouf_JClinPharmTher2017-28503727.pdf}, nlmuniqueid = {8704308} } @article{Bymaster2001, title = {Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors.}, author = {Bymaster, F P and Dreshfield-Ahmad, L J and Threlkeld, P G and Shaw, J L and Thompson, L and Nelson, D L and Hemrick-Luecke, S K and Wong, D T}, journal = {Neuropsychopharmacology}, volume = {25}, number = {6}, year = {2001}, month = {Dec}, pages = {871-80}, abstract = {The blockade of serotonin (5-HT) and norepinephrine (NE) transporters in vitro and in vivo by the dual 5-HT/NE reuptake inhibitors duloxetine and venlafaxine was compared. Duloxetine inhibited binding to the human NE and 5-HT transporters with K(i) values of 7.5 and 0.8 nM, respectively, and with a K(i) ratio of 9. Venlafaxine inhibited binding to the human NE and 5-HT transporters with K(i) values of 2480 and 82 nM, respectively, and with a K(i) ratio of 30. Duloxetine inhibited ex vivo binding to rat 5-HT transporters and NE transporters with ED(50) values of 0.03 and 0.7 mg/kg, respectively, whereas venlafaxine had ED(50) values of 2 and 54 mg/kg, respectively. The depletion of rat brain 5-HT by p-chloramphetamine and depletion of rat hypothalamic NE by 6-hydroxydopamine was blocked by duloxetine with ED(50) values of 2.3 and 12 mg/kg, respectively. Venlafaxine had ED(50) values of 5.9 and 94 mg/kg for blocking p-chloramphetamine- and 6-hydroxydopamine-induced monoamine depletion, respectively. Thus, duloxetine more potently blocks 5-HT and NE transporters in vitro and in vivo than venlafaxine.}, pmid = {11750180}, pii = {S0893133X01002986}, doi = {10.1016/S0893-133X(01)00298-6}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/11750180}, url = {papers/Bymaster_Neuropsychopharmacology2001-11750180.pdf}, nlmuniqueid = {8904907} } @article{Ray2010, title = {Psychedelics and the human receptorome.}, author = {Ray, Thomas S}, journal = {PLoS One}, volume = {5}, number = {2}, year = {2010}, month = {Feb}, pages = {e9019}, abstract = {We currently understand the mental effects of psychedelics to be caused by agonism or partial agonism of 5-HT(2A) (and possibly 5-HT(2C)) receptors, and we understand that psychedelic drugs, especially phenylalkylamines, are fairly selective for these two receptors. This manuscript is a reference work on the receptor affinity pharmacology of psychedelic drugs. New data is presented on the affinity of twenty-five psychedelic drugs at fifty-one receptors, transporters, and ion channels, assayed by the National Institute of Mental Health-Psychoactive Drug Screening Program (NIMH-PDSP). In addition, comparable data gathered from the literature on ten additional drugs is also presented (mostly assayed by the NIMH-PDSP). A new method is introduced for normalizing affinity (K(i)) data that factors out potency so that the multi-receptor affinity profiles of different drugs can be directly compared and contrasted. The method is then used to compare the thirty-five drugs in graphical and tabular form. It is shown that psychedelic drugs, especially phenylalkylamines, are not as selective as generally believed, interacting with forty-two of forty-nine broadly assayed sites. The thirty-five drugs of the study have very diverse patterns of interaction with different classes of receptors, emphasizing eighteen different receptors. This diversity of receptor interaction may underlie the qualitative diversity of these drugs. It should be possible to use this diverse set of drugs as probes into the roles played by the various receptor systems in the human mind.}, pmid = {20126400}, doi = {10.1371/journal.pone.0009019}, pmc = {PMC2814854}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/20126400}, url = {papers/Ray_PLoSOne2010-20126400.pdf}, nlmuniqueid = {101285081} } @article{Orsolini2017, title = {The "Endless Trip" among the NPS Users: Psychopathology and Psychopharmacology in the Hallucinogen-Persisting Perception Disorder. A Systematic Review.}, author = {Orsolini, Laura and Papanti, Gabriele Duccio and De Berardis, Domenico and Guirguis, Amira and Corkery, John Martin and Schifano, Fabrizio}, journal = {Front Psychiatry}, volume = {8}, year = {2017}, pages = {240}, abstract = {Hallucinogen-persisting perception disorder (HPPD) is a syndrome characterized by prolonged or reoccurring perceptual symptoms, reminiscent of acute hallucinogen effects. HPPD was associated with a broader range of LSD (lysergic acid diethylamide)-like substances, cannabis, methylenedioxymethamphetamine (MDMA), psilocybin, mescaline, and psychostimulants. The recent emergence of novel psychoactive substances (NPS) posed a critical concern regarding the new onset of psychiatric symptoms/syndromes, including cases of HPPD. Symptomatology mainly comprises visual disorders (i.e., geometric pseudo-hallucinations, haloes, flashes of colors/lights, motion-perception deficits, afterimages, micropsia, more acute awareness of floaters, etc.), even though depressive symptoms and thought disorders may be comorbidly present. Although HPPD was first described in 1954, it was just established as a fully syndrome in 2000, with the revised fourth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). HPPD neural substrates, risk factors, and aetiopathogenesys still largely remain unknown and under investigation, and many questions about its pharmacological targets remain unanswered too. A critical mini review on psychopathological bases, etiological hypothesis, and psychopharmacological approaches toward HPPD, including the association with some novel substances, are provided here, by means of a literature search on PubMed/Medline, Google Scholar, and Scopus databases without time restrictions, by using a specific set of keywords. Pharmacological and clinical issues are considered, and practical psychopharmacological recommendations and clinical guidelines are suggested.}, keywords = {flashbacks; hallucinations; hallucinogen-persisting perception disorder; hallucinogens; novel psychoactive substances; palinopsia; }, pmid = {29209235}, doi = {10.3389/fpsyt.2017.00240}, pmc = {PMC5701998}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/29209235}, url = {papers/Orsolini_FrontPsychiatry2017-29209235.pdf}, nlmuniqueid = {101545006} } @article{Carhart-Harris2017, title = {The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future.}, author = {Carhart-Harris, Robin L and Goodwin, Guy M}, journal = {Neuropsychopharmacology}, volume = {42}, number = {11}, year = {2017}, month = {Oct}, pages = {2105-2113}, abstract = {Plant-based psychedelics, such as psilocybin, have an ancient history of medicinal use. After the first English language report on LSD in 1950, psychedelics enjoyed a short-lived relationship with psychology and psychiatry. Used most notably as aids to psychotherapy for the treatment of mood disorders and alcohol dependence, drugs such as LSD showed initial therapeutic promise before prohibitive legislature in the mid-1960s effectively ended all major psychedelic research programs. Since the early 1990s, there has been a steady revival of human psychedelic research: last year saw reports on the first modern brain imaging study with LSD and three separate clinical trials of psilocybin for depressive symptoms. In this circumspective piece, RLC-H and GMG share their opinions on the promises and pitfalls of renewed psychedelic research, with a focus on the development of psilocybin as a treatment for depression.}, pmid = {28443617}, pii = {npp201784}, doi = {10.1038/npp.2017.84}, pmc = {PMC5603818}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/28443617}, url = {papers/Carhart-Harris_Neuropsychopharmacology2017-28443617.pdf}, nlmuniqueid = {8904907} } @article{Schenberg2018, title = {Psychedelic-Assisted Psychotherapy: A Paradigm Shift in Psychiatric Research and Development.}, author = {Schenberg, Eduardo Ekman}, journal = {Front Pharmacol}, volume = {9}, year = {2018}, pages = {733}, abstract = {Mental disorders are rising while development of novel psychiatric medications is declining. This stall in innovation has also been linked with intense debates on the current diagnostics and explanations for mental disorders, together constituting a paradigmatic crisis. A radical innovation is psychedelic-assisted psychotherapy (PAP): professionally supervised use of ketamine, MDMA, psilocybin, LSD and ibogaine as part of elaborated psychotherapy programs. Clinical results so far have shown safety and efficacy, even for "treatment resistant" conditions, and thus deserve increasing attention from medical, psychological and psychiatric professionals. But more than novel treatments, the PAP model also has important consequences for the diagnostics and explanation axis of the psychiatric crisis, challenging the discrete nosological entities and advancing novel explanations for mental disorders and their treatment, in a model considerate of social and cultural factors, including adversities, trauma, and the therapeutic potential of some non-ordinary states of consciousness.}, keywords = {LSD; MDMA; explanation in neuroscience; ibogaine; ketamine; psilocybin; psychedelic-assisted psychotherapy; states of consciousness; }, pmid = {30026698}, doi = {10.3389/fphar.2018.00733}, pmc = {PMC6041963}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/30026698}, url = {papers/Schenberg_FrontPharmacol2018-30026698.pdf}, nlmuniqueid = {101548923} } @article{Roseman2017, title = {Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression.}, author = {Roseman, Leor and Nutt, David J and Carhart-Harris, Robin L}, journal = {Front Pharmacol}, volume = {8}, year = {2017}, pages = {974}, abstract = {Introduction: It is a basic principle of the "psychedelic" treatment model that the quality of the acute experience mediates long-term improvements in mental health. In the present paper we sought to test this using data from a clinical trial assessing psilocybin for treatment-resistant depression (TRD). In line with previous reports, we hypothesized that the occurrence and magnitude of Oceanic Boundlessness (OBN) (sharing features with mystical-type experience) and Dread of Ego Dissolution (DED) (similar to anxiety) would predict long-term positive outcomes, whereas sensory perceptual effects would have negligible predictive value. Materials and Methods: Twenty patients with treatment resistant depression underwent treatment with psilocybin (two separate sessions: 10 and 25 mg psilocybin). The Altered States of Consciousness (ASC) questionnaire was used to assess the quality of experiences in the 25 mg psilocybin session. From the ASC, the dimensions OBN and DED were used to measure the mystical-type and challenging experiences, respectively. The Self-Reported Quick Inventory of Depressive Symptoms (QIDS-SR) at 5 weeks served as the endpoint clinical outcome measure, as in later time points some of the subjects had gone on to receive new treatments, thus confounding inferences. In a repeated measure ANOVA, Time was the within-subject factor (independent variable), with QIDS-SR as the within-subject dependent variable in baseline, 1-day, 1-week, 5-weeks. OBN and DED were independent variables. OBN-by-Time and DED-by-Time interactions were the primary outcomes of interest. Results: For the interaction of OBN and DED with Time (QIDS-SR as dependent variable), the main effect and the effects at each time point compared to baseline were all significant (p = 0.002 and p = 0.003, respectively, for main effects), confirming our main hypothesis. Furthermore, Pearson's correlation of OBN with QIDS-SR (5 weeks) was specific compared to perceptual dimensions of the ASC (p < 0.05). Discussion: This report further bolsters the view that the quality of the acute psychedelic experience is a key mediator of long-term changes in mental health. Future therapeutic work with psychedelics should recognize the essential importance of quality of experience in determining treatment efficacy and consider ways of enhancing mystical-type experiences and reducing anxiety. Trial Registration: ISRCTN, number ISRCTN14426797, http://www.isrctn.com/ISRCTN14426797.}, keywords = {depression; mystical experience; peak experience; psilocybin; psychedelics; serotonin; therapy; }, pmid = {29387009}, doi = {10.3389/fphar.2017.00974}, pmc = {PMC5776504}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/29387009}, url = {papers/Roseman_FrontPharmacol2017-29387009.pdf}, nlmuniqueid = {101548923} } @article{Koenig2015, title = {The anti-addiction drug ibogaine and the heart: a delicate relation.}, author = {Koenig, Xaver and Hilber, Karlheinz}, journal = {Molecules}, volume = {20}, number = {2}, year = {2015}, month = {Jan}, pages = {2208-28}, abstract = {The plant indole alkaloid ibogaine has shown promising anti-addictive properties in animal studies. Ibogaine is also anti-addictive in humans as the drug alleviates drug craving and impedes relapse of drug use. Although not licensed as therapeutic drug and despite safety concerns, ibogaine is currently used as an anti-addiction medication in alternative medicine in dozens of clinics worldwide. In recent years, alarming reports of life-threatening complications and sudden death cases, temporally associated with the administration of ibogaine, have been accumulating. These adverse reactions were hypothesised to be associated with ibogaine's propensity to induce cardiac arrhythmias. The aim of this review is to recapitulate the current knowledge about ibogaine's effects on the heart and the cardiovascular system, and to assess the cardiac risks associated with the use of this drug in anti- addiction therapy. The actions of 18-methoxycoronaridine (18-MC), a less toxic ibogaine congener with anti-addictive properties, are also considered. }, pmid = {25642835}, pii = {molecules20022208}, doi = {10.3390/molecules20022208}, pmc = {PMC4382526}, mid = {EMS62840}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/25642835}, url = {papers/Koenig_Molecules2015-25642835.pdf}, nlmuniqueid = {100964009} } @article{Saxena2020, title = {Localized semi-nonnegative matrix factorization (LocaNMF) of widefield calcium imaging data.}, author = {Saxena, Shreya and Kinsella, Ian and Musall, Simon and Kim, Sharon H and Meszaros, Jozsef and Thibodeaux, David N and Kim, Carla and Cunningham, John and Hillman, Elizabeth M C and Churchland, Anne and Paninski, Liam}, journal = {PLoS Comput Biol}, volume = {16}, number = {4}, year = {2020}, month = {04}, pages = {e1007791}, abstract = {Widefield calcium imaging enables recording of large-scale neural activity across the mouse dorsal cortex. In order to examine the relationship of these neural signals to the resulting behavior, it is critical to demix the recordings into meaningful spatial and temporal components that can be mapped onto well-defined brain regions. However, no current tools satisfactorily extract the activity of the different brain regions in individual mice in a data-driven manner, while taking into account mouse-specific and preparation-specific differences. Here, we introduce Localized semi-Nonnegative Matrix Factorization (LocaNMF), a method that efficiently decomposes widefield video data and allows us to directly compare activity across multiple mice by outputting mouse-specific localized functional regions that are significantly more interpretable than more traditional decomposition techniques. Moreover, it provides a natural subspace to directly compare correlation maps and neural dynamics across different behaviors, mice, and experimental conditions, and enables identification of task- and movement-related brain regions.}, pmid = {32282806}, doi = {10.1371/journal.pcbi.1007791}, pii = {PCOMPBIOL-D-19-01682}, pmc = {PMC7179949}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/32282806}, url = {papers/Saxena_PLoSComputBiol2020-32282806.pdf}, nlmuniqueid = {101238922} } @article{Botvinik-Nezer2020, title = {Variability in the analysis of a single neuroimaging dataset by many teams.}, author = {Botvinik-Nezer, Rotem and Holzmeister, Felix and Camerer, Colin F and Dreber, Anna and Huber, Juergen and Johannesson, Magnus and Kirchler, Michael and Iwanir, Roni and Mumford, Jeanette A and Adcock, R Alison and Avesani, Paolo and Baczkowski, Blazej M and Bajracharya, Aahana and Bakst, Leah and Ball, Sheryl and Barilari, Marco and Bault, Nadège and Beaton, Derek and Beitner, Julia and Benoit, Roland G and Berkers, Ruud M W J and Bhanji, Jamil P and Biswal, Bharat B and Bobadilla-Suarez, Sebastian and Bortolini, Tiago and Bottenhorn, Katherine L and Bowring, Alexander and Braem, Senne and Brooks, Hayley R and Brudner, Emily G and Calderon, Cristian B and Camilleri, Julia A and Castrellon, Jaime J and Cecchetti, Luca and Cieslik, Edna C and Cole, Zachary J and Collignon, Olivier and Cox, Robert W and Cunningham, William A and Czoschke, Stefan and Dadi, Kamalaker and Davis, Charles P and Luca, Alberto De and Delgado, Mauricio R and Demetriou, Lysia and Dennison, Jeffrey B and Di, Xin and Dickie, Erin W and Dobryakova, Ekaterina and Donnat, Claire L and Dukart, Juergen and Duncan, Niall W and Durnez, Joke and Eed, Amr and Eickhoff, Simon B and Erhart, Andrew and Fontanesi, Laura and Fricke, G Matthew and Fu, Shiguang and Galván, Adriana and Gau, Remi and Genon, Sarah and Glatard, Tristan and Glerean, Enrico and Goeman, Jelle J and Golowin, Sergej A E and González-García, Carlos and Gorgolewski, Krzysztof J and Grady, Cheryl L and Green, Mikella A and Guassi Moreira, João F and Guest, Olivia and Hakimi, Shabnam and Hamilton, J Paul and Hancock, Roeland and Handjaras, Giacomo and Harry, Bronson B and Hawco, Colin and Herholz, Peer and Herman, Gabrielle and Heunis, Stephan and Hoffstaedter, Felix and Hogeveen, Jeremy and Holmes, Susan and Hu, Chuan-Peng and Huettel, Scott A and Hughes, Matthew E and Iacovella, Vittorio and Iordan, Alexandru D and Isager, Peder M and Isik, Ayse I and Jahn, Andrew and Johnson, Matthew R and Johnstone, Tom and Joseph, Michael J E and Juliano, Anthony C and Kable, Joseph W and Kassinopoulos, Michalis and Koba, Cemal and Kong, Xiang-Zhen and Koscik, Timothy R and Kucukboyaci, Nuri Erkut and Kuhl, Brice A and Kupek, Sebastian and Laird, Angela R and Lamm, Claus and Langner, Robert and Lauharatanahirun, Nina and Lee, Hongmi and Lee, Sangil and Leemans, Alexander and Leo, Andrea and Lesage, Elise and Li, Flora and Li, Monica Y C and Lim, Phui Cheng and Lintz, Evan N and Liphardt, Schuyler W and Losecaat Vermeer, Annabel B and Love, Bradley C and Mack, Michael L and Malpica, Norberto and Marins, Theo and Maumet, Camille and McDonald, Kelsey and McGuire, Joseph T and Melero, Helena and Méndez Leal, Adriana S and Meyer, Benjamin and Meyer, Kristin N and Mihai, Glad and Mitsis, Georgios D and Moll, Jorge and Nielson, Dylan M and Nilsonne, Gustav and Notter, Michael P and Olivetti, Emanuele and Onicas, Adrian I and Papale, Paolo and Patil, Kaustubh R and Peelle, Jonathan E and Pérez, Alexandre and Pischedda, Doris and Poline, Jean-Baptiste and Prystauka, Yanina and Ray, Shruti and Reuter-Lorenz, Patricia A and Reynolds, Richard C and Ricciardi, Emiliano and Rieck, Jenny R and Rodriguez-Thompson, Anais M and Romyn, Anthony and Salo, Taylor and Samanez-Larkin, Gregory R and Sanz-Morales, Emilio and Schlichting, Margaret L and Schultz, Douglas H and Shen, Qiang and Sheridan, Margaret A and Silvers, Jennifer A and Skagerlund, Kenny and Smith, Alec and Smith, David V and Sokol-Hessner, Peter and Steinkamp, Simon R and Tashjian, Sarah M and Thirion, Bertrand and Thorp, John N and Tinghög, Gustav and Tisdall, Loreen and Tompson, Steven H and Toro-Serey, Claudio and Torre Tresols, Juan Jesus and Tozzi, Leonardo and Truong, Vuong and Turella, Luca and van 't Veer, Anna E and Verguts, Tom and Vettel, Jean M and Vijayarajah, Sagana and Vo, Khoi and Wall, Matthew B and Weeda, Wouter D and Weis, Susanne and White, David J and Wisniewski, David and Xifra-Porxas, Alba and Yearling, Emily A and Yoon, Sangsuk and Yuan, Rui and Yuen, Kenneth S L and Zhang, Lei and Zhang, Xu and Zosky, Joshua E and Nichols, Thomas E and Poldrack, Russell A and Schonberg, Tom}, journal = {Nature}, volume = {582}, number = {7810}, year = {2020}, month = {06}, pages = {84-88}, abstract = {Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.}, pmid = {32483374}, doi = {10.1038/s41586-020-2314-9}, pii = {10.1038/s41586-020-2314-9}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/32483374}, url = {papers/Botvinik-Nezer_Nature2020-32483374.pdf}, nlmuniqueid = {0410462} } @article{VanEssen2012, title = {Cortical cartography and Caret software.}, author = {Van Essen, David C}, journal = {Neuroimage}, volume = {62}, number = {2}, year = {2012}, month = {Aug}, pages = {757-64}, abstract = {Caret software is widely used for analyzing and visualizing many types of fMRI data, often in conjunction with experimental data from other modalities. This article places Caret's development in a historical context that spans three decades of brain mapping--from the early days of manually generated flat maps to the nascent field of human connectomics. It also highlights some of Caret's distinctive capabilities. This includes the ease of visualizing data on surfaces and/or volumes and on atlases as well as individual subjects. Caret can display many types of experimental data using various combinations of overlays (e.g., fMRI activation maps, cortical parcellations, areal boundaries), and it has other features that facilitate the analysis and visualization of complex neuroimaging datasets.}, pmid = {22062192}, pii = {S1053-8119(11)01241-9}, doi = {10.1016/j.neuroimage.2011.10.077}, pmc = {PMC3288593}, mid = {NIHMS335250}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/22062192}, url = {papers/VanEssen_Neuroimage2012-22062192.pdf}, nlmuniqueid = {9215515} } @article{Ioannidis2005, title = {Why most published research findings are false.}, author = {Ioannidis, John P A}, journal = {PLoS Med}, volume = {2}, number = {8}, year = {2005}, month = {Aug}, pages = {e124}, abstract = {There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.}, pmid = {16060722}, pii = {04-PLME-E-0321R2}, doi = {10.1371/journal.pmed.0020124}, pmc = {PMC1182327}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/16060722}, url = {papers/Ioannidis_PLoSMed2005-16060722.pdf}, nlmuniqueid = {101231360} } @article{Ioannidis2014, title = {How to make more published research true.}, author = {Ioannidis, John P A}, journal = {PLoS Med}, volume = {11}, number = {10}, year = {2014}, month = {Oct}, pages = {e1001747}, abstract = {In a 2005 paper that has been accessed more than a million times, John Ioannidis explained why most published research findings were false. Here he revisits the topic, this time to address how to improve matters. Please see later in the article for the Editors' Summary. }, pmid = {25334033}, doi = {10.1371/journal.pmed.1001747}, pii = {PMEDICINE-D-14-01145}, pmc = {PMC4204808}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/25334033}, url = {papers/Ioannidis_PLoSMed2014-25334033.pdf}, nlmuniqueid = {101231360} } @article{Barchi1995, title = {Molecular pathology of the skeletal muscle sodium channel.}, author = {Barchi, R L}, journal = {Annu Rev Physiol}, volume = {57}, year = {1995}, pages = {355-85}, pmid = {7778872}, doi = {10.1146/annurev.ph.57.030195.002035}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/7778872}, url = {papers/Barchi_AnnuRevPhysiol1995-7778872.pdf}, nlmuniqueid = {0370600} } @article{Hyvarinen2013, title = {Independent component analysis: recent advances.}, author = {Hyvärinen, Aapo}, journal = {Philos Trans A Math Phys Eng Sci}, volume = {371}, number = {1984}, year = {2013}, month = {Feb}, pages = {20110534}, abstract = {Independent component analysis is a probabilistic method for learning a linear transform of a random vector. The goal is to find components that are maximally independent and non-Gaussian (non-normal). Its fundamental difference to classical multi-variate statistical methods is in the assumption of non-Gaussianity, which enables the identification of original, underlying components, in contrast to classical methods. The basic theory of independent component analysis was mainly developed in the 1990s and summarized, for example, in our monograph in 2001. Here, we provide an overview of some recent developments in the theory since the year 2000. The main topics are: analysis of causal relations, testing independent components, analysing multiple datasets (three-way data), modelling dependencies between the components and improved methods for estimating the basic model.}, pmid = {23277597}, pii = {rsta.2011.0534}, doi = {10.1098/rsta.2011.0534}, pmc = {PMC3538438}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/23277597}, url = {papers/Hyvärinen_PhilosTransAMathPhysEngSci2013-23277597.pdf}, nlmuniqueid = {101133385} } @article{Hyvarinen2016, author = {Hyvärinen, Aapo and Morioka, Hiroshi}, title = {Unsupervised Feature Extraction by Time-Contrastive Learning and Nonlinear ICA}, journal = {arXiv}, year = {2016}, doi = {arXiv:1605.06336}, eprint = {https://arxiv.org/pdf/1605.06336.pdf}, url = {papers/Hyvarinen_arXiv2016.pdf} } @incollection{Du_2019, doi = {10.1007/978-1-4471-7452-3_2}, eprint = {https://doi.org/10.1007/2F978-1-4471-7452-3_2}, year = 2019, publisher = {Springer London}, pages = {21--63}, author = {Ke-Lin Du and M. N. S. Swamy}, title = {Fundamentals of Machine Learning}, booktitle = {Neural Networks and Statistical Learning}, url = {papers/2019_Book_NeuralNetworksAndStatisticalLe.pdf} } @article{Oja1982, title = {A simplified neuron model as a principal component analyzer.}, author = {Oja, E}, journal = {J Math Biol}, volume = {15}, number = {3}, year = {1982}, pages = {267-73}, pmid = {7153672}, doi = {10.1007/BF00275687}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/7153672}, url = {papers/Oja_JMathBiol1982-7153672.pdf}, nlmuniqueid = {7502105} } @book{Hyvarinen_2001, doi = {10.1002/0471221317}, eprint = {https://doi.org/10.1002/2F0471221317}, url2 = {https://onlinelibrary.wiley.com/doi/book/10.1002/0471221317}, year = {2001}, month = {may}, publisher = {John Wiley {\&} Sons, Inc.}, author = {Aapo Hyvärinen and Juha Karhunen and Erkki Oja}, title = {Independent Component Analysis}, url = {papers/Hyvarinen2001_bookfinal_ICA.pdf} } @book{2015_ICA_learning, doi = {10.1016/C2014-0-02754-2}, eprint = {https://doi.org/10.1016/C2014-0-02754-2}, url2 = {https://www.sciencedirect.com/book/9780128028063/advances-in-independent-component-analysis-and-learning-machines#book-description}, year = {2015}, publisher = {Elsevier}, author = {Bingham, Ella and Kaski, Samuel and Laaksonen, Jorma and Lampinen, Jouko}, title = {Advances in Independent Component Analysis and Learning Machines}, url = {papers/2015_Advances-in-Independent-Component-Analysis-and-Learning-Machines.pdf} } @article{Berkes2011, title = {Spontaneous cortical activity reveals hallmarks of an optimal internal model of the environment.}, author = {Berkes, Pietro and Orbán, Gergo and Lengyel, Máté and Fiser, József}, journal = {Science}, volume = {331}, number = {6013}, year = {2011}, month = {Jan}, pages = {83-7}, abstract = {The brain maintains internal models of its environment to interpret sensory inputs and to prepare actions. Although behavioral studies have demonstrated that these internal models are optimally adapted to the statistics of the environment, the neural underpinning of this adaptation is unknown. Using a Bayesian model of sensory cortical processing, we related stimulus-evoked and spontaneous neural activities to inferences and prior expectations in an internal model and predicted that they should match if the model is statistically optimal. To test this prediction, we analyzed visual cortical activity of awake ferrets during development. Similarity between spontaneous and evoked activities increased with age and was specific to responses evoked by natural scenes. This demonstrates the progressive adaptation of internal models to the statistics of natural stimuli at the neural level.}, pmid = {21212356}, pii = {331/6013/83}, doi = {10.1126/science.1195870}, pmc = {PMC3065813}, mid = {UKMS33678}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/21212356}, url = {papers/Berkes_Science2011-21212356.pdf}, nlmuniqueid = {0404511} } @article{Chestek2007, title = {Single-neuron stability during repeated reaching in macaque premotor cortex.}, author = {Chestek, Cynthia A and Batista, Aaron P and Santhanam, Gopal and Yu, Byron M and Afshar, Afsheen and Cunningham, John P and Gilja, Vikash and Ryu, Stephen I and Churchland, Mark M and Shenoy, Krishna V}, journal = {J Neurosci}, volume = {27}, number = {40}, year = {2007}, month = {Oct}, pages = {10742-50}, abstract = {Some movements that animals and humans make are highly stereotyped, repeated with little variation. The patterns of neural activity associated with repeats of a movement may be highly similar, or the same movement may arise from different patterns of neural activity, if the brain exploits redundancies in the neural projections to muscles. We examined the stability of the relationship between neural activity and behavior. We asked whether the variability in neural activity that we observed during repeated reaching was consistent with a noisy but stable relationship, or with a changing relationship, between neural activity and behavior. Monkeys performed highly similar reaches under tight behavioral control, while many neurons in the dorsal aspect of premotor cortex and the primary motor cortex were simultaneously monitored for several hours. Neural activity was predominantly stable over time in all measured properties: firing rate, directional tuning, and contribution to a decoding model that predicted kinematics from neural activity. The small changes in neural activity that we did observe could be accounted for primarily by subtle changes in behavior. We conclude that the relationship between neural activity and practiced behavior is reasonably stable, at least on timescales of minutes up to 48 h. This finding has significant implications for the design of neural prosthetic systems because it suggests that device recalibration need not be overly frequent, It also has implications for studies of neural plasticity because a stable baseline permits identification of nonstationary shifts.}, pmid = {17913908}, pii = {27/40/10742}, doi = {10.1523/JNEUROSCI.0959-07.2007}, pmc = {PMC6672821}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/17913908}, url = {papers/Chestek_JNeurosci2007-17913908.pdf}, nlmuniqueid = {8102140} } @article{Gămănuţ2018, title = {The Mouse Cortical Connectome, Characterized by an Ultra-Dense Cortical Graph, Maintains Specificity by Distinct Connectivity Profiles.}, author = {Gămănuţ, Răzvan and Kennedy, Henry and Toroczkai, Zoltán and Ercsey-Ravasz, Mária and Van Essen, David C and Knoblauch, Kenneth and Burkhalter, Andreas}, journal = {Neuron}, volume = {97}, number = {3}, year = {2018}, month = {02}, pages = {698-715.e10}, abstract = {The inter-areal wiring pattern of the mouse cerebral cortex was analyzed in relation to a refined parcellation of cortical areas. Twenty-seven retrograde tracer injections were made in 19 areas of a 47-area parcellation of the mouse neocortex. Flat mounts of the cortex and multiple histological markers enabled detailed counts of labeled neurons in individual areas. The observed log-normal distribution of connection weights to each cortical area spans 5 orders of magnitude and reveals a distinct connectivity profile for each area, analogous to that observed in macaques. The cortical network has a density of 97%, considerably higher than the 66% density reported in macaques. A weighted graph analysis reveals a similar global efficiency but weaker spatial clustering compared with that reported in macaques. The consistency, precision of the connectivity profile, density, and weighted graph analysis of the present data differ significantly from those obtained in earlier studies in the mouse.}, keywords = {anatomy; connectivity; log-normal; neocortex; retrograde; rodent; tract-tracing; Animals; Connectome; Female; Macaca; Male; Models, Neurological; Neocortex; Neural Pathways; Neuroanatomical Tract-Tracing Techniques; Species Specificity; }, pmid = {29420935}, pii = {S0896-6273(17)31185-6}, doi = {10.1016/j.neuron.2017.12.037}, pmc = {PMC5958229}, mid = {NIHMS931062}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/29420935}, url = {papers/Gămănuţ_Neuron2018-29420935.pdf}, nlmuniqueid = {8809320} } @article{Gomez-Marin2019, title = {The Life of Behavior.}, author = {Gomez-Marin, Alex and Ghazanfar, Asif A}, journal = {Neuron}, volume = {104}, number = {1}, year = {2019}, month = {10}, pages = {25-36}, abstract = {Neuroscience needs behavior. However, it is daunting to render the behavior of organisms intelligible without suppressing most, if not all, references to life. When animals are treated as passive stimulus-response, disembodied and identical machines, the life of behavior perishes. Here, we distill three biological principles (materiality, agency, and historicity), spell out their consequences for the study of animal behavior, and illustrate them with various examples from the literature. We propose to put behavior back into context, with the brain in a species-typical body and with the animal's body situated in the world; stamp Newtonian time with nested ontogenetic and phylogenetic processes that give rise to individuals with their own histories; and supplement linear cause-and-effect chains and information processing with circular loops of purpose and meaning. We believe that conceiving behavior in these ways is imperative for neuroscience.}, pmid = {31600513}, pii = {S0896-6273(19)30790-1}, doi = {10.1016/j.neuron.2019.09.017}, pmc = {PMC6873815}, mid = {NIHMS1543024}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/31600513}, url = {papers/Gomez-Marin_Neuron2019-31600513.pdf}, nlmuniqueid = {8809320} } @article{Mazade2019, title = {Synergy in Cortical Networks.}, author = {Mazade, Reece and Alonso, Jose Manuel}, journal = {Neuron}, volume = {104}, number = {2}, year = {2019}, month = {10}, pages = {184-185}, abstract = {A dot in this text can simultaneously stimulate thousands of neurons in primary visual cortex, a response that may seem unnecessarily redundant. Contrary to such a view, in this issue of Neuron, Nigam et al. (2019) demonstrate that these co-activated neurons generate abundant synergistic interactions that help to decode the stimulus.}, pmid = {31647891}, pii = {S0896-6273(19)30844-X}, doi = {10.1016/j.neuron.2019.09.041}, url = {papers/Mazade_Neuron2019-31647891.pdf}, nlmuniqueid = {8809320} } @article{Fujisawa2011, title = {A 4 Hz oscillation adaptively synchronizes prefrontal, VTA, and hippocampal activities.}, author = {Fujisawa, Shigeyoshi and Buzsáki, György}, journal = {Neuron}, volume = {72}, number = {1}, year = {2011}, month = {Oct}, pages = {153-65}, abstract = {Network oscillations support transient communication across brain structures. We show here, in rats, that task-related neuronal activity in the medial prefrontal cortex (PFC), the hippocampus, and the ventral tegmental area (VTA), regions critical for working memory, is coordinated by a 4 Hz oscillation. A prominent increase of power and coherence of the 4 Hz oscillation in the PFC and the VTA and its phase modulation of gamma power in both structures was present in the working memory part of the task. Subsets of both PFC and hippocampal neurons predicted the turn choices of the rat. The goal-predicting PFC pyramidal neurons were more strongly phase locked to both 4 Hz and hippocampal theta oscillations than nonpredicting cells. The 4 Hz and theta oscillations were phase coupled and jointly modulated both gamma waves and neuronal spikes in the PFC, the VTA, and the hippocampus. Thus, multiplexed timing mechanisms in the PFC-VTA-hippocampus axis may support processing of information, including working memory.}, pmid = {21982376}, pii = {S0896-6273(11)00739-2}, doi = {10.1016/j.neuron.2011.08.018}, pmc = {PMC3235795}, mid = {NIHMS321938}, url = {papers/Fujisawa_Neuron2011-21982376.pdf}, nlmuniqueid = {8809320} } @article{Sejnowski2020, title = {The unreasonable effectiveness of deep learning in artificial intelligence.}, author = {Sejnowski, Terrence J}, journal = {Proc Natl Acad Sci U S A}, volume = {117}, number = {48}, year = {2020}, month = {12}, pages = {30033-30038}, abstract = {Deep learning networks have been trained to recognize speech, caption photographs, and translate text between languages at high levels of performance. Although applications of deep learning networks to real-world problems have become ubiquitous, our understanding of why they are so effective is lacking. These empirical results should not be possible according to sample complexity in statistics and nonconvex optimization theory. However, paradoxes in the training and effectiveness of deep learning networks are being investigated and insights are being found in the geometry of high-dimensional spaces. A mathematical theory of deep learning would illuminate how they function, allow us to assess the strengths and weaknesses of different network architectures, and lead to major improvements. Deep learning has provided natural ways for humans to communicate with digital devices and is foundational for building artificial general intelligence. Deep learning was inspired by the architecture of the cerebral cortex and insights into autonomy and general intelligence may be found in other brain regions that are essential for planning and survival, but major breakthroughs will be needed to achieve these goals.}, keywords = {artificial intelligence; deep learning; neural networks; }, pmid = {31992643}, pii = {1907373117}, doi = {10.1073/pnas.1907373117}, pmc = {PMC7720171}, url = {papers/Sejnowski_ProcNatlAcadSciUSA2020-31992643.pdf}, nlmuniqueid = {7505876} } @article{Peters_2019, doi = {10.1038/s41567-019-0732-0}, eprint = {https://doi.org/10.1038%2Fs41567-019-0732-0}, year = 2019, month = {dec}, publisher = {Springer Science and Business Media {LLC}}, volume = {15}, number = {12}, pages = {1216--1221}, author = {Ole Peters}, title = {The ergodicity problem in economics}, journal = {Nature Physics}, url = {papers/Peters_NaturePhysics2019.pdf} } @article{Barson2020, title = {Simultaneous mesoscopic and two-photon imaging of neuronal activity in cortical circuits.}, author = {Barson, Daniel and Hamodi, Ali S and Shen, Xilin and Lur, Gyorgy and Constable, R Todd and Cardin, Jessica A and Crair, Michael C and Higley, Michael J}, journal = {Nat Methods}, volume = {17}, number = {1}, year = {2020}, month = {01}, pages = {107-113}, abstract = {Spontaneous and sensory-evoked activity propagates across varying spatial scales in the mammalian cortex, but technical challenges have limited conceptual links between the function of local neuronal circuits and brain-wide network dynamics. We present a method for simultaneous cellular-resolution two-photon calcium imaging of a local microcircuit and mesoscopic widefield calcium imaging of the entire cortical mantle in awake mice. Our multi-scale approach involves a microscope with an orthogonal axis design where the mesoscopic objective is oriented above the brain and the two-photon objective is oriented horizontally, with imaging performed through a microprism. We also introduce a viral transduction method for robust and widespread gene delivery in the mouse brain. These approaches allow us to identify the behavioral state-dependent functional connectivity of pyramidal neurons and vasoactive intestinal peptide-expressing interneurons with long-range cortical networks. Our imaging system provides a powerful strategy for investigating cortical architecture across a wide range of spatial scales.}, pmid = {31686040}, doi = {10.1038/s41592-019-0625-2}, pii = {10.1038/s41592-019-0625-2}, pmc = {PMC6946863}, mid = {NIHMS1540817}, url = {papers/Barson_NatMethods2020-31686040.pdf}, nlmuniqueid = {101215604} } @article{Zhu2018, title = {Decoding cortical brain states from widefield calcium imaging data using visibility graph.}, author = {Zhu, Li and Lee, Christian R and Margolis, David J and Najafizadeh, Laleh}, journal = {Biomed Opt Express}, volume = {9}, number = {7}, year = {2018}, month = {Jul}, pages = {3017-3036}, abstract = {Widefield optical imaging of neuronal populations over large portions of the cerebral cortex in awake behaving animals provides a unique opportunity for investigating the relationship between brain function and behavior. In this paper, we demonstrate that the temporal characteristics of calcium dynamics obtained through widefield imaging can be utilized to infer the corresponding behavior. Cortical activity in transgenic calcium reporter mice (n=6) expressing GCaMP6f in neocortical pyramidal neurons is recorded during active whisking (AW) and no whisking (NW). To extract features related to the temporal characteristics of calcium recordings, a method based on visibility graph (VG) is introduced. An extensive study considering different choices of features and classifiers is conducted to find the best model capable of predicting AW and NW from calcium recordings. Our experimental results show that temporal characteristics of calcium recordings identified by the proposed method carry discriminatory information that are powerful enough for decoding behavior.}, keywords = {(170.2655) Functional monitoring and imaging; (170.3880) Medical and biological imaging; }, pmid = {29984080}, doi = {10.1364/BOE.9.003017}, pii = {320299}, pmc = {PMC6033549}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/29984080}, url = {papers/Zhu_BiomedOptExpress2018-29984080.pdf}, nlmuniqueid = {101540630} } @article{Silasi2016, title = {Intact skull chronic windows for mesoscopic wide-field imaging in awake mice.}, author = {Silasi, Gergely and Xiao, Dongsheng and Vanni, Matthieu P and Chen, Andrew C N and Murphy, Timothy H}, journal = {J Neurosci Methods}, volume = {267}, year = {2016}, month = {07}, pages = {141-9}, abstract = {Craniotomy-based window implants are commonly used for microscopic imaging, in head-fixed rodents, however their field of view is typically small and incompatible with mesoscopic functional mapping of cortex.}, keywords = {GCaMP; Head-fixed; Optogenetics; Animals; Cerebral Cortex; Craniotomy; Dental Cements; Equipment Design; Glass; Grooming; Longitudinal Studies; Mice, Transgenic; Motor Activity; Neuroimaging; Optical Imaging; Optogenetics; Prostheses and Implants; Skull; Time Factors; Wakefulness; }, pmid = {27102043}, pmc = {PMC5075450}, pii = {S0165-0270(16)30064-4}, doi = {10.1016/j.jneumeth.2016.04.012}, mid = {CAMS6038}, url = {papers/Silasi_JNeurosciMethods2016-27102043.pdf}, nlmuniqueid = {7905558} } @article{Cramer2019, title = {In vivo widefield calcium imaging of the mouse cortex for analysis of network connectivity in health and brain disease.}, author = {Cramer, Julia V and Gesierich, Benno and Roth, Stefan and Dichgans, Martin and Düring, Marco and Liesz, Arthur}, journal = {Neuroimage}, volume = {199}, year = {2019}, month = {10}, pages = {570-584}, abstract = {The organization of brain areas in functionally connected networks, their dynamic changes, and perturbations in disease states are subject of extensive investigations. Research on functional networks in humans predominantly uses functional magnetic resonance imaging (fMRI). However, adopting fMRI and other functional imaging methods to mice, the most widely used model to study brain physiology and disease, poses major technical challenges and faces important limitations. Hence, there is great demand for alternative imaging modalities for network characterization. Here, we present a refined protocol for in vivo widefield calcium imaging of both cerebral hemispheres in mice expressing a calcium sensor in excitatory neurons. We implemented a stringent protocol for minimizing anesthesia and excluding movement artifacts which both imposed problems in previous approaches. We further adopted a method for unbiased identification of functional cortical areas using independent component analysis (ICA) on resting-state imaging data. Biological relevance of identified components was confirmed using stimulus-dependent cortical activation. To explore this novel approach in a model of focal brain injury, we induced photothrombotic lesions of the motor cortex, determined changes in inter- and intrahemispheric connectivity at multiple time points up to 56 days post-stroke and correlated them with behavioral deficits. We observed a severe loss in interhemispheric connectivity after stroke, which was partially restored in the chronic phase and associated with corresponding behavioral motor deficits. Taken together, we present an improved widefield calcium imaging tool accounting for anesthesia and movement artifacts, adopting an advanced analysis pipeline based on human fMRI algorithms and with superior sensitivity to recovery mechanisms in mouse models compared to behavioral tests. This tool will enable new studies on interhemispheric connectivity in murine models with comparability to human imaging studies for a wide spectrum of neuroscience applications in health and disease.}, keywords = {ICA; In vivo imaging; Mouse models; Neuronal network connectivity; Recovery; Stroke; Animals; Calcium; Cerebral Cortex; Connectome; Disease Models, Animal; Female; Male; Mice; Mice, Inbred C57BL; Motor Cortex; Nerve Net; Neuroimaging; Optical Imaging; Prosencephalon; Stroke; }, pmid = {31181333}, pii = {S1053-8119(19)30499-9}, doi = {10.1016/j.neuroimage.2019.06.014}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/31181333}, url = {papers/Cramer_Neuroimage2019-31181333.pdf}, nlmuniqueid = {9215515} } @article{Shore2020, title = {Reduced GABAergic Neuron Excitability, Altered Synaptic Connectivity, and Seizures in a KCNT1 Gain-of-Function Mouse Model of Childhood Epilepsy.}, author = {Shore, Amy N and Colombo, Sophie and Tobin, William F and Petri, Sabrina and Cullen, Erin R and Dominguez, Soledad and Bostick, Christopher D and Beaumont, Michael A and Williams, Damian and Khodagholy, Dion and Yang, Mu and Lutz, Cathleen M and Peng, Yueqing and Gelinas, Jennifer N and Goldstein, David B and Boland, Michael J and Frankel, Wayne N and Weston, Matthew C}, journal = {Cell Rep}, volume = {33}, number = {4}, year = {2020}, month = {10}, pages = {108303}, abstract = {Gain-of-function (GOF) variants in K+ channels cause severe childhood epilepsies, but there are no mechanisms to explain how increased K+ currents lead to network hyperexcitability. Here, we introduce a human Na+-activated K+ (KNa) channel variant (KCNT1-Y796H) into mice and, using a multiplatform approach, find motor cortex hyperexcitability and early-onset seizures, phenotypes strikingly similar to those of human patients. Although the variant increases KNa currents in cortical excitatory and inhibitory neurons, there is an increase in the KNa current across subthreshold voltages only in inhibitory neurons, particularly in those with non-fast-spiking properties, resulting in inhibitory-neuron-specific impairments in excitability and action potential (AP) generation. We further observe evidence of synaptic rewiring, including increases in homotypic synaptic connectivity, accompanied by network hyperexcitability and hypersynchronicity. These findings support inhibitory-neuron-specific mechanisms in mediating the epileptogenic effects of KCNT1 channel GOF, offering cell-type-specific currents and effects as promising targets for therapeutic intervention.}, keywords = {ADNFLE; K(Na) current; KCNT1; MEA; Slack; calcium imaging; electrocorticography; electrophysiology; epilepsy; synaptic transmission; }, pmid = {33113364}, pii = {S2211-1247(20)31292-4}, doi = {10.1016/j.celrep.2020.108303}, pmc = {PMC7712469}, mid = {NIHMS1642113}, url = {papers/Shore_CellRep2020-33113364.pdf}, nlmuniqueid = {101573691} } @article{Murphy2020, title = {Automated task training and longitudinal monitoring of mouse mesoscale cortical circuits using home cages.}, author = {Murphy, Timothy H and Michelson, Nicholas J and Boyd, Jamie D and Fong, Tony and Bolanos, Luis A and Bierbrauer, David and Siu, Teri and Balbi, Matilde and Bolanos, Federico and Vanni, Matthieu and LeDue, Jeff M}, journal = {Elife}, volume = {9}, year = {2020}, month = {05}, pages = {}, abstract = {We report improved automated open-source methodology for head-fixed mesoscale cortical imaging and/or behavioral training of home cage mice using Raspberry Pi-based hardware. Staged partial and probabilistic restraint allows mice to adjust to self-initiated headfixation over 3 weeks' time with ~50% participation rate. We support a cue-based behavioral licking task monitored by a capacitive touch-sensor water spout. While automatically head-fixed, we acquire spontaneous, movement-triggered, or licking task-evoked GCaMP6 cortical signals. An analysis pipeline marked both behavioral events, as well as analyzed brain fluorescence signals as they relate to spontaneous and/or task-evoked behavioral activity. Mice were trained to suppress licking and wait for cues that marked the delivery of water. Correct rewarded go-trials were associated with widespread activation of midline and lateral barrel cortex areas following a vibration cue and delayed frontal and lateral motor cortex activation. Cortical GCaMP signals predicted trial success and correlated strongly with trial-outcome dependent body movements.}, keywords = {automation; cortex; homecage; imaging; mesoscale; mouse; neuroscience; Animals; Behavior, Animal; Brain Mapping; Calcium-Binding Proteins; Cues; Drinking; Equipment Design; Female; Head Movements; Luminescent Proteins; Male; Mice, Inbred C57BL; Mice, Transgenic; Motor Cortex; Optical Imaging; Restraint, Physical; Reward; Time Factors; }, pmid = {32412409}, doi = {10.7554/eLife.55964}, pii = {55964}, pmc = {PMC7332290}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/32412409}, url = {papers/Murphy_Elife2020-32412409.pdf}, nlmuniqueid = {101579614} } @article{Lake2020, title = {Simultaneous cortex-wide fluorescence Ca2+ imaging and whole-brain fMRI.}, author = {Lake, Evelyn M R and Ge, Xinxin and Shen, Xilin and Herman, Peter and Hyder, Fahmeed and Cardin, Jessica A and Higley, Michael J and Scheinost, Dustin and Papademetris, Xenophon and Crair, Michael C and Constable, R Todd}, journal = {Nat Methods}, volume = {17}, number = {12}, year = {2020}, month = {12}, pages = {1262-1271}, abstract = {Achieving a comprehensive understanding of brain function requires multiple imaging modalities with complementary strengths. We present an approach for concurrent widefield optical and functional magnetic resonance imaging. By merging these modalities, we can simultaneously acquire whole-brain blood-oxygen-level-dependent (BOLD) and whole-cortex calcium-sensitive fluorescent measures of brain activity. In a transgenic murine model, we show that calcium predicts the BOLD signal, using a model that optimizes a gamma-variant transfer function. We find consistent predictions across the cortex, which are best at low frequency (0.009-0.08 Hz). Furthermore, we show that the relationship between modality connectivity strengths varies by region. Our approach links cell-type-specific optical measurements of activity to the most widely used method for assessing human brain function.}, pmid = {33139894}, doi = {10.1038/s41592-020-00984-6}, pii = {10.1038/s41592-020-00984-6}, pmc = {PMC7704940}, mid = {NIHMS1631388}, url = {papers/Lake_NatMethods2020-33139894.pdf}, nlmuniqueid = {101215604} } @article{Valley2020, title = {Separation of hemodynamic signals from GCaMP fluorescence measured with wide-field imaging.}, author = {Valley, M T and Moore, M G and Zhuang, J and Mesa, N and Castelli, D and Sullivan, D and Reimers, M and Waters, J}, journal = {J Neurophysiol}, volume = {123}, number = {1}, year = {2020}, month = {01}, pages = {356-366}, abstract = {Wide-field calcium imaging is often used to measure brain dynamics in behaving mice. With a large field of view and a high sampling rate, wide-field imaging can monitor activity from several distant cortical areas simultaneously, revealing cortical interactions. Interpretation of wide-field images is complicated, however, by the absorption of light by hemoglobin, which can substantially affect the measured fluorescence. One approach to separating hemodynamics and calcium signals is to use multiwavelength backscatter recordings to measure light absorption by hemoglobin. Following this approach, we develop a spatially detailed regression-based method to estimate hemodynamics. This Spatial Model is based on a linear form of the Beer-Lambert relationship but is fit at every pixel in the image and does not rely on the estimation of physical parameters. In awake mice of three transgenic lines, the Spatial Model offers improved separation of hemodynamics and changes in GCaMP fluorescence. The improvement is pronounced near blood vessels and, in contrast with the Beer-Lambert equations, can remove vascular artifacts along the sagittal midline and in general permits more accurate fluorescence-based determination of neuronal activity across the cortex.NEW & NOTEWORTHY This paper addresses a well-known and strong source of contamination in wide-field calcium-imaging data: hemodynamics. To guide researchers toward the best method to separate calcium signals from hemodynamics, we compare the performance of several methods in three commonly used mouse lines and present a novel regression model that outperforms the other techniques we consider.}, keywords = {animal behavior; calcium imaging; hemodynamics; optical methods; systems neuroscience; }, pmid = {31747332}, doi = {10.1152/jn.00304.2019}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/31747332}, url = {papers/Valley_JNeurophysiol2020-31747332.pdf}, nlmuniqueid = {0375404} } @article{Aruljothi2020, title = {Functional Localization of an Attenuating Filter within Cortex for a Selective Detection Task in Mice.}, author = {Aruljothi, Krithiga and Marrero, Krista and Zhang, Zhaoran and Zareian, Behzad and Zagha, Edward}, journal = {J Neurosci}, volume = {40}, number = {28}, year = {2020}, month = {07}, pages = {5443-5454}, abstract = {An essential feature of goal-directed behavior is the ability to selectively respond to the diverse stimuli in one's environment. However, the neural mechanisms that enable us to respond to target stimuli while ignoring distractor stimuli are poorly understood. To study this sensory selection process, we trained male and female mice in a selective detection task in which mice learn to respond to rapid stimuli in the target whisker field and ignore identical stimuli in the opposite, distractor whisker field. In expert mice, we used widefield Ca2+ imaging to analyze target-related and distractor-related neural responses throughout dorsal cortex. For target stimuli, we observed strong signal activation in primary somatosensory cortex (S1) and frontal cortices, including both the whisker region of primary motor cortex (wMC) and anterior lateral motor cortex (ALM). For distractor stimuli, we observed strong signal activation in S1, with minimal propagation to frontal cortex. Our data support only modest subcortical filtering, with robust, step-like attenuation in distractor processing between mono-synaptically coupled regions of S1 and wMC. This study establishes a highly robust model system for studying the neural mechanisms of sensory selection and places important constraints on its implementation.SIGNIFICANCE STATEMENT Responding to task-relevant stimuli while ignoring task-irrelevant stimuli is critical for goal-directed behavior. However, the neural mechanisms involved in this selection process are poorly understood. We trained mice in a detection task with both target and distractor stimuli. During expert performance, we measured neural activity throughout cortex using widefield imaging. We observed responses to target stimuli in multiple sensory and motor cortical regions. In contrast, responses to distractor stimuli were abruptly suppressed beyond sensory cortex. Our findings localize the sites of attenuation when successfully ignoring a distractor stimulus and provide essential foundations for further revealing the neural mechanism of sensory selection and distractor suppression.}, keywords = {attenuating filter; neocortex; sensorimotor; sensory selection; somatosensory; widefield imaging; Animals; Attention; Female; Male; Mice; Motor Cortex; Physical Stimulation; Reaction Time; Somatosensory Cortex; Touch Perception; Vibrissae; }, pmid = {32487695}, pii = {JNEUROSCI.2993-19.2020}, doi = {10.1523/JNEUROSCI.2993-19.2020}, pmc = {PMC7343319}, url = {papers/Aruljothi_JNeurosci2020-32487695.pdf}, nlmuniqueid = {8102140} } @article{Nobre2020, title = {Under the Mind's Hood: What We Have Learned by Watching the Brain at Work.}, author = {Nobre, Anna Christina and van Ede, Freek}, journal = {J Neurosci}, volume = {40}, number = {1}, year = {2020}, month = {01}, pages = {89-100}, abstract = {Imagine you were asked to investigate the workings of an engine, but to do so without ever opening the hood. Now imagine the engine fueled the human mind. This is the challenge faced by cognitive neuroscientists worldwide aiming to understand the neural bases of our psychological functions. Luckily, human ingenuity comes to the rescue. Around the same time as the Society for Neuroscience was being established in the 1960s, the first tools for measuring the human brain at work were becoming available. Noninvasive human brain imaging and neurophysiology have continued developing at a relentless pace ever since. In this 50 year anniversary, we reflect on how these methods have been changing our understanding of how brain supports mind.}, keywords = {Electroencephalograhy (EEG); Functional Magnetic Resonance Imaging (fMRI); Historical overview; Human brain imaging; Human neurophysiology; Selective attention; Attention; Brain Mapping; Cognition; Evoked Potentials; Forecasting; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Machine Learning; Mental Processes; Neuroimaging; Neurophysiology; Neuropsychology; Psychophysiology; }, pmid = {31630115}, pii = {JNEUROSCI.0742-19.2019}, doi = {10.1523/JNEUROSCI.0742-19.2019}, pmc = {PMC6939481}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/31630115}, url = {papers/Nobre_JNeurosci2020-31630115.pdf}, nlmuniqueid = {8102140} } @article{Vu2018, title = {A Shared Vision for Machine Learning in Neuroscience.}, author = {Vu, Mai-Anh T and Adalı, Tülay and Ba, Demba and Buzsáki, György and Carlson, David and Heller, Katherine and Liston, Conor and Rudin, Cynthia and Sohal, Vikaas S and Widge, Alik S and Mayberg, Helen S and Sapiro, Guillermo and Dzirasa, Kafui}, journal = {J Neurosci}, volume = {38}, number = {7}, year = {2018}, month = {02}, pages = {1601-1607}, abstract = {With ever-increasing advancements in technology, neuroscientists are able to collect data in greater volumes and with finer resolution. The bottleneck in understanding how the brain works is consequently shifting away from the amount and type of data we can collect and toward what we actually do with the data. There has been a growing interest in leveraging this vast volume of data across levels of analysis, measurement techniques, and experimental paradigms to gain more insight into brain function. Such efforts are visible at an international scale, with the emergence of big data neuroscience initiatives, such as the BRAIN initiative (Bargmann et al., 2014), the Human Brain Project, the Human Connectome Project, and the National Institute of Mental Health's Research Domain Criteria initiative. With these large-scale projects, much thought has been given to data-sharing across groups (Poldrack and Gorgolewski, 2014; Sejnowski et al., 2014); however, even with such data-sharing initiatives, funding mechanisms, and infrastructure, there still exists the challenge of how to cohesively integrate all the data. At multiple stages and levels of neuroscience investigation, machine learning holds great promise as an addition to the arsenal of analysis tools for discovering how the brain works.}, keywords = {explainable artificial intelligence; machine learning; reinforcement learning; Animals; Big Data; Brain; Connectome; Humans; Information Dissemination; Machine Learning; Neurosciences; Reproducibility of Results; }, pmid = {29374138}, pii = {JNEUROSCI.0508-17.2018}, doi = {10.1523/JNEUROSCI.0508-17.2018}, pmc = {PMC5815449}, url = {papers/Vu_JNeurosci2018-29374138.pdf}, nlmuniqueid = {8102140} } @article{Huk2018, title = {Beyond Trial-Based Paradigms: Continuous Behavior, Ongoing Neural Activity, and Natural Stimuli.}, author = {Huk, Alexander and Bonnen, Kathryn and He, Biyu J}, journal = {J Neurosci}, volume = {38}, number = {35}, year = {2018}, month = {08}, pages = {7551-7558}, abstract = {The vast majority of experiments examining perception and behavior are conducted using experimental paradigms that adhere to a rigid trial structure: each trial consists of a brief and discrete series of events and is regarded as independent from all other trials. The assumptions underlying this structure ignore the reality that natural behavior is rarely discrete, brain activity follows multiple time courses that do not necessarily conform to the trial structure, and the natural environment has statistical structure and dynamics that exhibit long-range temporal correlation. Modern advances in statistical modeling and analysis offer tools that make it feasible for experiments to move beyond rigid independent and identically distributed trial structures. Here we review literature that serves as evidence for the feasibility and advantages of moving beyond trial-based paradigms to understand the neural basis of perception and cognition. Furthermore, we propose a synthesis of these efforts, integrating the characterization of natural stimulus properties with measurements of continuous neural activity and behavioral outputs within the framework of sensory-cognitive-motor loops. Such a framework provides a basis for the study of natural statistics, naturalistic tasks, and/or slow fluctuations in brain activity, which should provide starting points for important generalizations of analytical tools in neuroscience and subsequent progress in understanding the neural basis of perception and cognition.}, pmid = {30037835}, pii = {JNEUROSCI.1920-17.2018}, doi = {10.1523/JNEUROSCI.1920-17.2018}, pmc = {PMC6113904}, url = {papers/Huk_JNeurosci2018-30037835.pdf}, nlmuniqueid = {8102140} } @article{Lecoq2019, title = {Wide. Fast. Deep: Recent Advances in Multiphoton Microscopy of In Vivo Neuronal Activity.}, author = {Lecoq, Jérôme and Orlova, Natalia and Grewe, Benjamin F}, journal = {J Neurosci}, volume = {39}, number = {46}, year = {2019}, month = {11}, pages = {9042-9052}, abstract = {Multiphoton microscopy (MPM) has emerged as one of the most powerful and widespread technologies to monitor the activity of neuronal networks in awake, behaving animals over long periods of time. MPM development spanned across decades and crucially depended on the concurrent improvement of calcium indicators that report neuronal activity as well as surgical protocols, head fixation approaches, and innovations in optics and microscopy technology. Here we review the last decade of MPM development and highlight how in vivo imaging has matured and diversified, making it now possible to concurrently monitor thousands of neurons across connected brain areas or, alternatively, small local networks with sampling rates in the kilohertz range. This review includes different laser scanning approaches, such as multibeam technologies as well as recent developments to image deeper into neuronal tissues using new, long-wavelength laser sources. As future development will critically depend on our ability to resolve and discriminate individual neuronal spikes, we will also describe a simple framework that allows performing quantitative comparisons between the reviewed MPM instruments. Finally, we provide our own opinion on how the most recent MPM developments can be leveraged at scale to enable the next generation of discoveries in brain function.}, keywords = {imaging; in vivo; multiphoton; two-photon; Animals; Brain; Image Processing, Computer-Assisted; Microscopy, Confocal; Microscopy, Fluorescence, Multiphoton; Neurons; }, pmid = {31578235}, pii = {JNEUROSCI.1527-18.2019}, doi = {10.1523/JNEUROSCI.1527-18.2019}, pmc = {PMC6855689}, url = {papers/Lecoq_JNeurosci2019-31578235.pdf}, nlmuniqueid = {8102140} } @article{Bassett2017, title = {Network neuroscience.}, author = {Bassett, Danielle S and Sporns, Olaf}, journal = {Nat Neurosci}, volume = {20}, number = {3}, year = {2017}, month = {Feb}, pages = {353-364}, abstract = {Despite substantial recent progress, our understanding of the principles and mechanisms underlying complex brain function and cognition remains incomplete. Network neuroscience proposes to tackle these enduring challenges. Approaching brain structure and function from an explicitly integrative perspective, network neuroscience pursues new ways to map, record, analyze and model the elements and interactions of neurobiological systems. Two parallel trends drive the approach: the availability of new empirical tools to create comprehensive maps and record dynamic patterns among molecules, neurons, brain areas and social systems; and the theoretical framework and computational tools of modern network science. The convergence of empirical and computational advances opens new frontiers of scientific inquiry, including network dynamics, manipulation and control of brain networks, and integration of network processes across spatiotemporal domains. We review emerging trends in network neuroscience and attempt to chart a path toward a better understanding of the brain as a multiscale networked system.}, pmid = {28230844}, pii = {nn.4502}, doi = {10.1038/nn.4502}, pmc = {PMC5485642}, mid = {NIHMS855763}, eprint = {https://www.ncbi.nlm.nih.gov/pubmed/28230844}, url = {papers/Bassett_NatNeurosci2017-28230844.pdf}, nlmuniqueid = {9809671} } @article{Gomez-Marin2021, title = {Promisomics and the Short-Circuiting of Mind.}, author = {Gomez-Marin, Alex}, journal = {eNeuro}, volume = {8}, number = {2}, pages = {}, keywords = {cognition; connectomics; levels of analysis; promissory materialism; }, pmid = {33648976}, pii = {ENEURO.0521-20.2021}, doi = {10.1523/ENEURO.0521-20.2021}, url = {papers/Gomez-Marin_eNeuro-33648976.pdf}, nlmuniqueid = {101647362} } @article{nnMethodsFocus2020, title = {Focus on neuroscience methods.}, journal = {Nat Neurosci}, volume = {23}, number = {12}, year = {2020}, month = {12}, pages = {1455}, pmid = {33230327}, doi = {10.1038/s41593-020-00750-z}, pii = {10.1038/s41593-020-00750-z}, url = {papers/_NatNeurosci2020-33230327.pdf}, nlmuniqueid = {9809671} } @article{Yuste2020, title = {A community-based transcriptomics classification and nomenclature of neocortical cell types.}, author = {Yuste, Rafael and Hawrylycz, Michael and Aalling, Nadia and Aguilar-Valles, Argel and Arendt, Detlev and Armañanzas, Ruben and Ascoli, Giorgio A and Bielza, Concha and Bokharaie, Vahid and Bergmann, Tobias Borgtoft and Bystron, Irina and Capogna, Marco and Chang, YoonJeung and Clemens, Ann and de Kock, Christiaan P J and DeFelipe, Javier and Dos Santos, Sandra Esmeralda and Dunville, Keagan and Feldmeyer, Dirk and Fiáth, Richárd and Fishell, Gordon James and Foggetti, Angelica and Gao, Xuefan and Ghaderi, Parviz and Goriounova, Natalia A and Güntürkün, Onur and Hagihara, Kenta and Hall, Vanessa Jane and Helmstaedter, Moritz and Herculano-Houzel, Suzana and Hilscher, Markus M and Hirase, Hajime and Hjerling-Leffler, Jens and Hodge, Rebecca and Huang, Josh and Huda, Rafiq and Khodosevich, Konstantin and Kiehn, Ole and Koch, Henner and Kuebler, Eric S and Kühnemund, Malte and Larrañaga, Pedro and Lelieveldt, Boudewijn and Louth, Emma Louise and Lui, Jan H and Mansvelder, Huibert D and Marin, Oscar and Martinez-Trujillo, Julio and Chameh, Homeira Moradi and Mohapatra, Alok Nath and Munguba, Hermany and Nedergaard, Maiken and Němec, Pavel and Ofer, Netanel and Pfisterer, Ulrich Gottfried and Pontes, Samuel and Redmond, William and Rossier, Jean and Sanes, Joshua R and Scheuermann, Richard H and Serrano-Saiz, Esther and Staiger, Jochen F and Somogyi, Peter and Tamás, Gábor and Tolias, Andreas Savas and Tosches, Maria Antonietta and García, Miguel Turrero and Wozny, Christian and Wuttke, Thomas V and Liu, Yong and Yuan, Juan and Zeng, Hongkui and Lein, Ed}, journal = {Nat Neurosci}, volume = {23}, number = {12}, year = {2020}, month = {12}, pages = {1456-1468}, abstract = {To understand the function of cortical circuits, it is necessary to catalog their cellular diversity. Past attempts to do so using anatomical, physiological or molecular features of cortical cells have not resulted in a unified taxonomy of neuronal or glial cell types, partly due to limited data. Single-cell transcriptomics is enabling, for the first time, systematic high-throughput measurements of cortical cells and generation of datasets that hold the promise of being complete, accurate and permanent. Statistical analyses of these data reveal clusters that often correspond to cell types previously defined by morphological or physiological criteria and that appear conserved across cortical areas and species. To capitalize on these new methods, we propose the adoption of a transcriptome-based taxonomy of cell types for mammalian neocortex. This classification should be hierarchical and use a standardized nomenclature. It should be based on a probabilistic definition of a cell type and incorporate data from different approaches, developmental stages and species. A community-based classification and data aggregation model, such as a knowledge graph, could provide a common foundation for the study of cortical circuits. This community-based classification, nomenclature and data aggregation could serve as an example for cell type atlases in other parts of the body.}, pmid = {32839617}, doi = {10.1038/s41593-020-0685-8}, pii = {10.1038/s41593-020-0685-8}, pmc = {PMC7683348}, mid = {NIHMS1627961}, url = {papers/Yuste_NatNeurosci2020-32839617.pdf}, nlmuniqueid = {9809671} } @article{Comiskey1998, doi = {10.1038/28349}, url = {papers/Comiskey_Nature1998.pdf}, year = {1998}, month = {jul}, publisher = {Springer Science and Business Media {LLC}}, volume = {394}, number = {6690}, pages = {253--255}, author = {Barrett Comiskey and J. D. Albert and Hidekazu Yoshizawa and Joseph Jacobson}, title = {An electrophoretic ink for all-printed reflective electronic displays}, journal = {Nature} } @article{MacVicar2015, title = {Astrocyte regulation of blood flow in the brain.}, author = {MacVicar, Brian A and Newman, Eric A}, journal = {Cold Spring Harb Perspect Biol}, volume = {7}, number = {5}, year = {2015}, month = {Mar}, pages = {}, abstract = {Neuronal activity results in increased blood flow in the brain, a response named functional hyperemia. Astrocytes play an important role in mediating this response. Neurotransmitters released from active neurons evoke Ca(2+) increases in astrocytes, leading to the release of vasoactive metabolites of arachidonic acid from astrocyte endfeet onto blood vessels. Synthesis of prostaglandin E2 (PGE2) and epoxyeicosatrienoic acids (EETs) dilate blood vessels, whereas 20-hydroxyeicosatetraenoic acid (20-HETE) constricts vessels. The release of K(+) from astrocyte endfeet may also contribute to vasodilation. Oxygen modulates astrocyte regulation of blood flow. Under normoxic conditions, astrocytic Ca(2+) signaling results in vasodilation, whereas under hyperoxic conditions, vasoconstriction is favored. Astrocytes also contribute to the generation of vascular tone. Tonic release of both 20-HETE and ATP from astrocytes constricts vascular smooth muscle cells, generating vessel tone. Under pathological conditions, including Alzheimer's disease and diabetic retinopathy, disruption of normal astrocyte physiology can compromise the regulation of blood flow. }, pmid = {25818565}, pii = {cshperspect.a020388}, doi = {10.1101/cshperspect.a020388}, pmc = {PMC4448617}, url = {papers/MacVicar_ColdSpringHarbPerspectBiol2015-25818565.pdf}, nlmuniqueid = {101513680} } @article{Attwell2010, title = {Glial and neuronal control of brain blood flow.}, author = {Attwell, David and Buchan, Alastair M and Charpak, Serge and Lauritzen, Martin and Macvicar, Brian A and Newman, Eric A}, journal = {Nature}, volume = {468}, number = {7321}, year = {2010}, month = {Nov}, pages = {232-43}, abstract = {Blood flow in the brain is regulated by neurons and astrocytes. Knowledge of how these cells control blood flow is crucial for understanding how neural computation is powered, for interpreting functional imaging scans of brains, and for developing treatments for neurological disorders. It is now recognized that neurotransmitter-mediated signalling has a key role in regulating cerebral blood flow, that much of this control is mediated by astrocytes, that oxygen modulates blood flow regulation, and that blood flow may be controlled by capillaries as well as by arterioles. These conceptual shifts in our understanding of cerebral blood flow control have important implications for the development of new therapeutic approaches.}, pmid = {21068832}, pii = {nature09613}, doi = {10.1038/nature09613}, pmc = {PMC3206737}, mid = {NIHMS272381}, url = {papers/Attwell_Nature2010-21068832.pdf}, nlmuniqueid = {0410462} } @article{Angelova2015, title = {Functional Oxygen Sensitivity of Astrocytes.}, author = {Angelova, Plamena R and Kasymov, Vitaliy and Christie, Isabel and Sheikhbahaei, Shahriar and Turovsky, Egor and Marina, Nephtali and Korsak, Alla and Zwicker, Jennifer and Teschemacher, Anja G and Ackland, Gareth L and Funk, Gregory D and Kasparov, Sergey and Abramov, Andrey Y and Gourine, Alexander V}, journal = {J Neurosci}, volume = {35}, number = {29}, year = {2015}, month = {Jul}, pages = {10460-73}, abstract = {In terrestrial mammals, the oxygen storage capacity of the CNS is limited, and neuronal function is rapidly impaired if oxygen supply is interrupted even for a short period of time. However, oxygen tension monitored by the peripheral (arterial) chemoreceptors is not sensitive to regional CNS differences in partial pressure of oxygen (PO2 ) that reflect variable levels of neuronal activity or local tissue hypoxia, pointing to the necessity of a functional brain oxygen sensor. This experimental animal (rats and mice) study shows that astrocytes, the most numerous brain glial cells, are sensitive to physiological changes in PO2 . Astrocytes respond to decreases in PO2 a few millimeters of mercury below normal brain oxygenation with elevations in intracellular calcium ([Ca(2+)]i). The hypoxia sensor of astrocytes resides in the mitochondria in which oxygen is consumed. Physiological decrease in PO2 inhibits astroglial mitochondrial respiration, leading to mitochondrial depolarization, production of free radicals, lipid peroxidation, activation of phospholipase C, IP3 receptors, and release of Ca(2+) from the intracellular stores. Hypoxia-induced [Ca(2+)]i increases in astrocytes trigger fusion of vesicular compartments containing ATP. Blockade of astrocytic signaling by overexpression of ATP-degrading enzymes or targeted astrocyte-specific expression of tetanus toxin light chain (to interfere with vesicular release mechanisms) within the brainstem respiratory rhythm-generating circuits reveals the fundamental physiological role of astroglial oxygen sensitivity; in low-oxygen conditions (environmental hypoxia), this mechanism increases breathing activity even in the absence of peripheral chemoreceptor oxygen sensing. These results demonstrate that astrocytes are functionally specialized CNS oxygen sensors tuned for rapid detection of physiological changes in brain oxygenation. Significance statement: Most, if not all, animal cells possess mechanisms that allow them to detect decreases in oxygen availability leading to slow-timescale, adaptive changes in gene expression and cell physiology. To date, only two types of mammalian cells have been demonstrated to be specialized for rapid functional oxygen sensing: glomus cells of the carotid body (peripheral respiratory chemoreceptors) that stimulate breathing when oxygenation of the arterial blood decreases; and pulmonary arterial smooth muscle cells responsible for hypoxic pulmonary vasoconstriction to limit perfusion of poorly ventilated regions of the lungs. Results of the present study suggest that there is another specialized oxygen-sensitive cell type in the body, the astrocyte, that is tuned for rapid detection of physiological changes in brain oxygenation.}, keywords = {astrocyte; glia; hypoxia; oxygen; respiration; Animals; Astrocytes; Cell Hypoxia; Cells, Cultured; Chemoreceptor Cells; Immunohistochemistry; Male; Mice; Mice, Knockout; Organ Culture Techniques; Oxygen; Rats; Rats, Sprague-Dawley; Respiratory Physiological Phenomena; }, pmid = {26203141}, pii = {35/29/10460}, doi = {10.1523/JNEUROSCI.0045-15.2015}, pmc = {PMC4510287}, url = {papers/Angelova_JNeurosci2015-26203141.pdf}, nlmuniqueid = {8102140} } @article{Takano2006, title = {Astrocyte-mediated control of cerebral blood flow.}, author = {Takano, Takahiro and Tian, Guo-Feng and Peng, Weiguo and Lou, Nanhong and Libionka, Witold and Han, Xiaoning and Nedergaard, Maiken}, journal = {Nat Neurosci}, volume = {9}, number = {2}, year = {2006}, month = {Feb}, pages = {260-7}, abstract = {Local increase in blood flow during neural activity forms the basis for functional brain imaging, but its mechanism remains poorly defined. Here we show that cortical astrocytes in vivo possess a powerful mechanism for rapid vasodilation. We imaged the activity of astrocytes labeled with the calcium (Ca(2+))-sensitive indicator rhod-2 in somatosensory cortex of adult mice. Photolysis of caged Ca(2+) in astrocytic endfeet ensheathing the vessel wall was associated with an 18% increase in arterial cross-section area that corresponded to a 37% increase in blood flow. Vasodilation occurred with a latency of only 1-2 s, and both indomethacin and the cyclooxygenase-1 inhibitor SC-560 blocked the photolysis-induced hyperemia. These observations implicate astrocytes in the control of local microcirculation and suggest that one of their physiological roles is to mediate vasodilation in response to increased neural activity.}, pmid = {16388306}, pii = {nn1623}, doi = {10.1038/nn1623}, url = {papers/Takano_NatNeurosci2006-16388306.pdf}, nlmuniqueid = {9809671} } @article{Halassa2007, title = {Synaptic islands defined by the territory of a single astrocyte.}, author = {Halassa, Michael M and Fellin, Tommaso and Takano, Hajime and Dong, Jing-Hui and Haydon, Philip G}, journal = {J Neurosci}, volume = {27}, number = {24}, year = {2007}, month = {Jun}, pages = {6473-7}, abstract = {In the mammalian brain, astrocytes modulate neuronal function, in part, by synchronizing neuronal firing and coordinating synaptic networks. Little, however, is known about how this is accomplished from a structural standpoint. To investigate the structural basis of astrocyte-mediated neuronal synchrony and synaptic coordination, the three-dimensional relationships between cortical astrocytes and neurons was investigated. Using a transgenic and viral approach to label astrocytes with enhanced green fluorescent protein, we performed a three-dimensional reconstruction of astrocytes from tissue sections or live animals in vivo. We found that cortical astrocytes occupy nonoverlapping territories similar to those described in the hippocampus. Using immunofluorescence labeling of neuronal somata, a single astrocyte enwraps on average four neuronal somata with an upper limit of eight. Single-neuron dye-fills allowed us to estimate that one astrocyte contacts 300-600 neuronal dendrites. Together with the recent findings showing that glial Ca2+ signaling is restricted to individual astrocytes in vivo, and that Ca2+ signaling leads to gliotransmission, we propose the concept of functional islands of synapses in which groups of synapses confined within the boundaries of an individual astrocyte are modulated by the gliotransmitter environment controlled by that astrocyte. Our description offers a new structurally based conceptual framework to evaluate functional data involving interactions between neurons and astrocytes in the mammalian brain.}, keywords = {Animals; Astrocytes; Cell Communication; Cerebral Cortex; Dendrites; Glial Fibrillary Acidic Protein; Green Fluorescent Proteins; Humans; Imaging, Three-Dimensional; In Vitro Techniques; Mice; Mice, Transgenic; Neurons; Synapses; Synaptic Transmission; Transduction, Genetic; Vesicle-Associated Membrane Protein 2; }, pmid = {17567808}, pii = {27/24/6473}, doi = {10.1523/JNEUROSCI.1419-07.2007}, pmc = {PMC6672436}, url = {papers/Halassa_JNeurosci2007-17567808.pdf}, nlmuniqueid = {8102140} } @article{Court2004, title = {Restricted growth of Schwann cells lacking Cajal bands slows conduction in myelinated nerves.}, author = {Court, Felipe A and Sherman, Diane L and Pratt, Thomas and Garry, Emer M and Ribchester, Richard R and Cottrell, David F and Fleetwood-Walker, Susan M and Brophy, Peter J}, journal = {Nature}, volume = {431}, number = {7005}, year = {2004}, month = {Sep}, pages = {191-5}, abstract = {Nerve impulses are propagated at nodes of Ranvier in the myelinated nerves of vertebrates. Internodal distances have been proposed to affect the velocity of nerve impulse conduction; however, direct evidence is lacking, and the cellular mechanisms that might regulate the length of the myelinated segments are unknown. Ramón y Cajal described longitudinal and transverse bands of cytoplasm or trabeculae in internodal Schwann cells and suggested that they had a nutritive function. Here we show that internodal growth in wild-type nerves is precisely matched to nerve extension, but disruption of the cytoplasmic bands in Periaxin-null mice impairs Schwann cell elongation during nerve growth. By contrast, myelination proceeds normally. The capacity of wild-type and mutant Schwann cells to elongate is cell-autonomous, indicating that passive stretching can account for the lengthening of the internode during limb growth. As predicted on theoretical grounds, decreased internodal distances strikingly decrease conduction velocities and so affect motor function. We propose that microtubule-based transport in the longitudinal bands of Cajal permits internodal Schwann cells to lengthen in response to axonal growth, thus ensuring rapid nerve impulse transmission.}, keywords = {Animals; Axons; Behavior, Animal; Cell Size; Cytoplasm; Gene Deletion; Membrane Proteins; Mice; Mice, Knockout; Microtubules; Muscle, Skeletal; Myelin Basic Protein; Nerve Fibers, Myelinated; RNA, Messenger; Schwann Cells; Sciatic Nerve; Synaptic Transmission; }, pubmed = {15356632}, doi = {10.1038/nature02841}, pii = {nature02841}, url = {papers/Court_Nature2004-15356632.pdf}, nlmuniqueid = {0410462} } @article{Otsu2015, title = {Calcium dynamics in astrocyte processes during neurovascular coupling.}, author = {Otsu, Yo and Couchman, Kiri and Lyons, Declan G and Collot, Mayeul and Agarwal, Amit and Mallet, Jean-Maurice and Pfrieger, Frank W and Bergles, Dwight E and Charpak, Serge}, journal = {Nat Neurosci}, volume = {18}, number = {2}, year = {2015}, month = {Feb}, pages = {210-8}, abstract = {Enhanced neuronal activity in the brain triggers a local increase in blood flow, termed functional hyperemia, via several mechanisms, including calcium (Ca(2+)) signaling in astrocytes. However, recent in vivo studies have questioned the role of astrocytes in functional hyperemia because of the slow and sparse dynamics of their somatic Ca(2+) signals and the absence of glutamate metabotropic receptor 5 in adults. Here, we reexamined their role in neurovascular coupling by selectively expressing a genetically encoded Ca(2+) sensor in astrocytes of the olfactory bulb. We show that in anesthetized mice, the physiological activation of olfactory sensory neuron (OSN) terminals reliably triggers Ca(2+) increases in astrocyte processes but not in somata. These Ca(2+) increases systematically precede the onset of functional hyperemia by 1-2 s, reestablishing astrocytes as potential regulators of neurovascular coupling. }, keywords = {Animals; Astrocytes; Calcium Signaling; Cerebrovascular Circulation; Mice; Mice, Transgenic; Olfactory Bulb; Olfactory Receptor Neurons; Receptor, Metabotropic Glutamate 5; Synapses; }, pubmed = {25531572}, pii = {nn.3906}, doi = {10.1038/nn.3906}, pmc = {PMC4651918}, mid = {NIHMS671426}, url = {papers/Otsu_NatNeurosci2015-25531572.pdf}, nlmuniqueid = {9809671} } @article{Kast2019, title = {Precision in the development of neocortical architecture: From progenitors to cortical networks.}, author = {Kast, Ryan J and Levitt, Pat}, journal = {Prog Neurobiol}, volume = {175}, year = {2019}, month = {04}, pages = {77-95}, abstract = {Of all brain regions, the 6-layered neocortex has undergone the most dramatic changes in size and complexity during mammalian brain evolution. These changes, occurring in the context of a conserved set of organizational features that emerge through stereotypical developmental processes, are considered responsible for the cognitive capacities and sensory specializations represented within the mammalian clade. The modern experimental era of developmental neurobiology, spanning 6 decades, has deciphered a number of mechanisms responsible for producing the diversity of cortical neuron types, their precise connectivity and the role of gene by environment interactions. Here, experiments providing insight into the development of cortical projection neuron differentiation and connectivity are reviewed. This current perspective integrates discussion of classic studies and new findings, based on recent technical advances, to highlight an improved understanding of the neuronal complexity and precise connectivity of cortical circuitry. These descriptive advances bring new opportunities for studies related to the developmental origins of cortical circuits that will, in turn, improve the prospects of identifying pathogenic targets of neurodevelopmental disorders.}, keywords = {Axon guidance; Cell type specification; Cerebral cortex; Circuits; Connectivity; Excitatory neurons; Experience; Genetics; Histogenesis; Human; Microcircuit; Neural network; Refinement; Reprogramming; Rodent; Specification; Synaptic specificity; Synaptogenesis; Thalamus; Animals; Humans; Neocortex; Nerve Net; Neural Pathways; Neural Stem Cells; Neurogenesis; Neurons; }, pubmed = {30677429}, pii = {S0301-0082(18)30136-9}, doi = {10.1016/j.pneurobio.2019.01.003}, pmc = {PMC6402587}, mid = {NIHMS1520766}, url = {papers/Kast_ProgNeurobiol2019-30677429.pdf}, nlmuniqueid = {0370121} } @article{McGuire1991, title = {Targets of horizontal connections in macaque primary visual cortex.}, author = {McGuire, B A and Gilbert, C D and Rivlin, P K and Wiesel, T N}, journal = {J Comp Neurol}, volume = {305}, number = {3}, year = {1991}, month = {Mar}, pages = {370-92}, abstract = {Pyramidal neurons within the cerebral cortex are known to make long-range horizontal connections via an extensive axonal collateral system. The synaptic characteristics and specificities of these connections were studied at the ultrastructural level. Two superficial layer pyramidal cells in the primate striate cortex were labeled by intracellular injections with horseradish peroxidase (HRP) and their axon terminals were subsequently examined with the technique of electron microscopic (EM) serial reconstruction. At the light microscopic level both cells showed the characteristic pattern of widespread, clustered axon collaterals. We examined collateral clusters located near the dendritic field (proximal) and approximately 0.5 mm away (distal). The synapses were of the asymmetric/round vesicle variety (type I), and were therefore presumably excitatory. Three-quarters of the postsynaptic targets were the dendritic spines of other pyramidal cells. A few of the axodendritic synapses were with the shafts of pyramidal cells, bringing the proportion of pyramidal cell targets to 80%. The remaining labeled endings were made with the dendritic shafts of smooth stellate cells, which are presumed to be (GABA)ergic inhibitory cells. On the basis of serial reconstruction of a few of these cells and their dendrites, a likely candidate for one target inhibitory cell is the small-medium basket cell. Taken together, this pattern of outputs suggests a mixture of postsynaptic effects mediated by consequence the horizontal connections may well be the substrate for the variety of influences observed between the receptive field center and its surround.}, keywords = {Animals; Axonal Transport; Axons; Cerebral Cortex; Dendrites; Horseradish Peroxidase; Macaca fascicularis; Microscopy, Electron; Pyramidal Tracts; Synapses; Visual Cortex; }, pubmed = {1709953}, doi = {10.1002/cne.903050303}, url = {papers/McGuire_JCompNeurol1991-1709953.pdf}, nlmuniqueid = {0406041} } @article{Wilson1973, title = {A mathematical theory of the functional dynamics of cortical and thalamic nervous tissue.}, author = {Wilson, H R and Cowan, J D}, journal = {Kybernetik}, volume = {13}, number = {2}, year = {1973}, month = {Sep}, pages = {55-80}, keywords = {Animals; Cerebral Cortex; Cybernetics; Electrophysiology; Humans; Mathematics; Models, Neurological; Rabbits; Thalamus; }, pubmed = {4767470}, doi = {10.1007/BF00288786}, url = {papers/Wilson_Kybernetik1973-4767470.pdf}, nlmuniqueid = {7502604} } @article{Rockland1982, title = {Anatomical binding of intrinsic connections in striate cortex of tree shrews (Tupaia glis).}, author = {Rockland, K S and Lund, J S and Humphrey, A L}, journal = {J Comp Neurol}, volume = {209}, number = {1}, year = {1982}, month = {Jul}, pages = {41-58}, abstract = {The intrinsic connectivity of striate cortex was investigated by injecting horseradish peroxidase (HRP) into this area in tree shrews. Such HRP injections demonstrated periodically organized, stripelike connections within area 17. These stripes occur in layers I-IIIA and consist of a small number or retrogradely filled neurons, some clearly pyramidal, together with HRP-labeled axon terminals. HRP-filled axons trunks run between labeled stripes, interconnecting adjacent and distant regions of the stripe pattern. Correlation with Golgi-stained tissue suggests that these stripes are horizontally interconnected by pyramidal neurons with long intracortical axon collaterals (followed for distances over 1 mm from the soma). The HRP-labeled strips measure about 230 micrometers in width, with a center-to-center repeat distance of 450--500 micrometers. They have been mapped over an 8 mm2 area of striate cortex and would thus seem capable of effecting lateral interactions over considerable portions of the retinotopic map. In their dimensions and overall pattern, these anatomical stripes resemble the 2-deoxyglucose (2-DG) bands resulting from visual stimulation of trees shrews with stripes of a single orientation. While the functional role of the HRP-labeled stripes is unclear, their similarities with the 2-DG pattern raise the intriguing possibility that they may be related to orientation selectivity. The striking regularity of these extensive lateral interconnections emphasizes the importance of horizontal intralaminar connections within the cortex.}, keywords = {Animals; Autoradiography; Brain Mapping; Corpus Callosum; Deoxyglucose; Genetic Variation; Horseradish Peroxidase; Tupaia; Tupaiidae; Visual Cortex; }, pubmed = {7119173}, doi = {10.1002/cne.902090105}, url = {papers/Rockland_JCompNeurol1982-7119173.pdf}, nlmuniqueid = {0406041} } @article{Mallot1996, title = {Population networks: a large-scale framework for modelling cortical neural networks.}, author = {Mallot, H A and Giannakopoulos, F}, journal = {Biol Cybern}, volume = {75}, number = {6}, year = {1996}, month = {Dec}, pages = {441-52}, abstract = {Artificial neural networks are usually built on rather few elements such as activation functions, learning rules, and the network topology. When modelling the more complex properties of realistic networks, however, a number of higher-level structural principles become important. In this paper we present a theoretical framework for modelling cortical networks at a high level of abstraction. Based on the notion of a population of neurons, this framework can accommodate the common features of cortical architecture, such as lamination, multiple areas and topographic maps, input segregation, and local variations of the frequency of different cell types (e.g., cytochrome oxidase blobs). The framework is meant primarily for the simulation of activation dynamics; it can also be used to model the neural environment of single cells in a multiscale approach.}, keywords = {Animals; Cerebral Cortex; Cybernetics; Feedback; Humans; Mathematics; Models, Neurological; Nerve Net; Neural Networks, Computer; Thalamus; Visual Cortex; }, pubmed = {9008348}, doi = {10.1007/s004220050309}, url = {papers/Mallot_BiolCybern1996-9008348.pdf}, nlmuniqueid = {7502533} } @article{Gilbert1983, title = {Clustered intrinsic connections in cat visual cortex.}, author = {Gilbert, C D and Wiesel, T N}, journal = {J Neurosci}, volume = {3}, number = {5}, year = {1983}, month = {May}, pages = {1116-33}, abstract = {The intrinsic connections of the cortex have long been known to run vertically, across the cortical layers. In the present study we have found that individual neurons in the cat primary visual cortex can communicate over suprisingly long distances horizontally (up to 4 mm), in directions parallel to the cortical surface. For all of the cells having widespread projections, the collaterals within their axonal fields were distributed in repeating clusters, with an average periodicity of 1 mm. This pattern of extensive clustered projections has been revealed by combining the techniques of intracellular recording and injection of horseradish peroxidase with three-dimensional computer graphic reconstructions. The clustering pattern was most apparent when the cells were rotated to present a view parallel to the cortical surface. The pattern was observed in more than half of the pyramidal and spiny stellate cells in the cortex and was seen in all cortical layers. In our sample, cells made distant connections within their own layer and/or within another layer. The axon of one cell had clusters covering the same area in two layers, and the clusters in the deeper layer were located under those in the upper layer, suggesting a relationship between the clustering phenomenon and columnar cortical architecture. Some pyramidal cells did not project into the white matter, forming intrinsic connections exclusively. Finally, the axonal fields of all our injected cells were asymmetric, extending for greater distances along one cortical axis than along the orthogonal axis. The axons appeared to cover areas of cortex representing a larger part of the visual field than that covered by the excitatory portion of the cell's own receptive field. These connections may be used to generate larger receptive fields or to produce the inhibitory flanks in other cells' receptive fields.}, keywords = {Animals; Axonal Transport; Cats; Horseradish Peroxidase; Pyramidal Tracts; Visual Cortex; }, pubmed = {6188819}, pmc = {PMC6564507}, url = {papers/Gilbert_JNeurosci1983-6188819.pdf}, nlmuniqueid = {8102140} } @article{Destexhe2009, title = {The Wilson-Cowan model, 36 years later.}, author = {Destexhe, Alain and Sejnowski, Terrence J}, journal = {Biol Cybern}, volume = {101}, number = {1}, year = {2009}, month = {Jul}, pages = {1-2}, abstract = {The Wilson-Cowan model of interacting neurons (1973) is one of the most influential papers published in Biological Cybernetics (Kybernetik). This paper and a companion paper published in 1972 have been cited over 1000 times. Rather than focus on the microscopic properties of neurons, Wilson and Cowan analyzed the collective properties of large numbers of neurons using methods from statistical mechanics, based on the mean-field approach. New experimental techniques to measure neuronal activity at the level of large populations are now available to test these models, including optical recording of brain activity with intrinsic signals and voltage sensitive dyes, and new methods for analyzing EEG and MEG. These measurement techniques have revealed patterns of coherent activity that span centimetres of tissue in the cerebral cortex. Here the underlying ideas are reviewed in a historic context.}, keywords = {Animals; Humans; Models, Neurological; Nerve Net; Neurons; }, pubmed = {19662434}, doi = {10.1007/s00422-009-0328-3}, pmc = {PMC2866289}, mid = {HHMIMS199370}, url = {papers/Destexhe_BiolCybern2009-19662434.pdf}, nlmuniqueid = {7502533} } @article{Herculano-Houzel2019, title = {Longevity and sexual maturity vary across species with number of cortical neurons, and humans are no exception.}, author = {Herculano-Houzel, Suzana}, journal = {J Comp Neurol}, volume = {527}, number = {10}, year = {2019}, month = {07}, pages = {1689-1705}, abstract = {Maximal longevity of endotherms has long been considered to increase with decreasing specific metabolic rate, and thus with increasing body mass. Using a dataset of over 700 species, here I show that maximal longevity, age at sexual maturity, and postmaturity longevity across bird and mammalian species instead correlate primarily, and universally, with the number of cortical brain neurons. Correlations with metabolic rate and body mass are entirely explained by clade-specific relationships between these variables and numbers of cortical neurons across species. Importantly, humans reach sexual maturity and subsequently live just as long as expected for their number of cortical neurons, which eliminates the basis for earlier theories of protracted childhood and prolonged post-menopause longevity as derived human characteristics. Longevity might increase together with numbers of cortical neurons through their impact on three main factors: delay of sexual maturity, which postpones the onset of aging; lengthening of the period of viable physiological integration and adaptation, which increases postmaturity longevity; and improved cognitive capabilities that benefit survival of the self and of longer-lived progeny, and are conducive to prolonged learning and cultural transmission through increased generational overlap. Importantly, the findings indicate that theories of aging and neurodegenerative diseases should take absolute time lived besides relative "age" into consideration.}, keywords = {AnAge; body size; cerebral cortex; longevity; metabolic rate; number of neurons; scaling; sexual maturity; Aging; Animals; Cerebral Cortex; Female; Humans; Longevity; Male; Neurons; Sexual Maturation; Species Specificity; }, pubmed = {30350858}, doi = {10.1002/cne.24564}, url = {papers/Herculano-Houzel_JCompNeurol2019-30350858.pdf}, nlmuniqueid = {0406041} } @article{Ren2021, title = {Characterizing Cortex-Wide Dynamics with Wide-Field Calcium Imaging.}, author = {Ren, Chi and Komiyama, Takaki}, journal = {J Neurosci}, volume = {41}, number = {19}, year = {2021}, month = {May}, pages = {4160-4168}, abstract = {The brain functions through coordinated activity among distributed regions. Wide-field calcium imaging, combined with improved genetically encoded calcium indicators, allows sufficient signal-to-noise ratio and spatiotemporal resolution to afford a unique opportunity to capture cortex-wide dynamics on a moment-by-moment basis in behaving animals. Recent applications of this approach have been uncovering cortical dynamics at unprecedented scales during various cognitive processes, ranging from relatively simple sensorimotor integration to more complex decision-making tasks. In this review, we will highlight recent scientific advances enabled by wide-field calcium imaging in behaving mice. We then summarize several technical considerations and future opportunities for wide-field imaging to uncover large-scale circuit dynamics.}, pubmed = {33893217}, pii = {JNEUROSCI.3003-20.2021}, doi = {10.1523/JNEUROSCI.3003-20.2021}, url = {papers/Ren_JNeurosci2021-33893217.pdf}, nlmuniqueid = {8102140} } @article{Mortensen2014, title = {Quantitative relationships in delphinid neocortex.}, author = {Mortensen, Heidi S and Pakkenberg, Bente and Dam, Maria and Dietz, Rune and Sonne, Christian and Mikkelsen, Bjarni and Eriksen, Nina}, journal = {Front Neuroanat}, volume = {8}, year = {2014}, pages = {132}, abstract = {Possessing large brains and complex behavioral patterns, cetaceans are believed to be highly intelligent. Their brains, which are the largest in the Animal Kingdom and have enormous gyrification compared with terrestrial mammals, have long been of scientific interest. Few studies, however, report total number of brain cells in cetaceans, and even fewer have used unbiased counting methods. In this study, using stereological methods, we estimated the total number of cells in the neocortex of the long-finned pilot whale (Globicephala melas) brain. For the first time, we show that a species of dolphin has more neocortical neurons than any mammal studied to date including humans. These cell numbers are compared across various mammals with different brain sizes, and the function of possessing many neurons is discussed. We found that the long-finned pilot whale neocortex has approximately 37.2 × 10(9) neurons, which is almost twice as many as humans, and 127 × 10(9) glial cells. Thus, the absolute number of neurons in the human neocortex is not correlated with the superior cognitive abilities of humans (at least compared to cetaceans) as has previously been hypothesized. However, as neuron density in long-finned pilot whales is lower than that in humans, their higher cell number appears to be due to their larger brain. Accordingly, our findings make an important contribution to the ongoing debate over quantitative relationships in the mammalian brain. }, pubmed = {25505387}, doi = {10.3389/fnana.2014.00132}, pmc = {PMC4244864}, url = {papers/Mortensen_FrontNeuroanat2014-25505387.pdf}, nlmuniqueid = {101477943} } @article{Herculano-Houzel2015, title = {Mammalian Brains Are Made of These: A Dataset of the Numbers and Densities of Neuronal and Nonneuronal Cells in the Brain of Glires, Primates, Scandentia, Eulipotyphlans, Afrotherians and Artiodactyls, and Their Relationship with Body Mass.}, author = {Herculano-Houzel, Suzana and Catania, Kenneth and Manger, Paul R and Kaas, Jon H}, journal = {Brain Behav Evol}, volume = {86}, number = {3-4}, year = {2015}, pages = {145-63}, abstract = {Comparative studies amongst extant species are one of the pillars of evolutionary neurobiology. In the 20th century, most comparative studies remained restricted to analyses of brain structure volume and surface areas, besides estimates of neuronal density largely limited to the cerebral cortex. Over the last 10 years, we have amassed data on the numbers of neurons and other cells that compose the entirety of the brain (subdivided into cerebral cortex, cerebellum, and rest of brain) of 39 mammalian species spread over 6 clades, as well as their densities. Here we provide that entire dataset in a format that is readily useful to researchers of any area of interest in the hope that it will foster the advancement of evolutionary and comparative studies well beyond the scope of neuroscience itself. We also reexamine the relationship between numbers of neurons, neuronal densities and body mass, and find that in the rest of brain, but not in the cerebral cortex or cerebellum, there is a single scaling rule that applies to average neuronal cell size, which increases with the linear dimension of the body, even though there is no single scaling rule that relates the number of neurons in the rest of brain to body mass. Thus, larger bodies do not uniformly come with more neurons--but they do fairly uniformly come with larger neurons in the rest of brain, which contains a number of structures directly connected to sources or targets in the body.}, keywords = {Animals; Artiodactyla; Biological Evolution; Body Size; Brain; Cell Count; Cell Size; Mammals; Neuroglia; Neurons; Primates; Scandentia; }, pubmed = {26418466}, pii = {000437413}, doi = {10.1159/000437413}, url = {papers/Herculano-Houzel_BrainBehavEvol2015-26418466.pdf}, nlmuniqueid = {0151620} } @article{Collins2016, title = {Cortical cell and neuron density estimates in one chimpanzee hemisphere.}, author = {Collins, Christine E and Turner, Emily C and Sawyer, Eva Kille and Reed, Jamie L and Young, Nicole A and Flaherty, David K and Kaas, Jon H}, journal = {Proc Natl Acad Sci U S A}, volume = {113}, number = {3}, year = {2016}, month = {Jan}, pages = {740-5}, abstract = {The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm(2) of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates. }, keywords = {flow fractionator; isotropic fractionator; neuron density; primate neocortex; visual cortex; Aging; Animals; Cell Count; Female; Motor Cortex; Neocortex; Neurons; Pan troglodytes; Somatosensory Cortex; Visual Cortex; }, pubmed = {26729880}, pii = {1524208113}, doi = {10.1073/pnas.1524208113}, pmc = {PMC4725503}, url = {papers/Collins_ProcNatlAcadSciUSA2016-26729880.pdf}, nlmuniqueid = {7505876} } @article{Herculano-Houzel2014, title = {The elephant brain in numbers.}, author = {Herculano-Houzel, Suzana and Avelino-de-Souza, Kamilla and Neves, Kleber and Porfírio, Jairo and Messeder, Débora and Mattos Feijó, Larissa and Maldonado, José and Manger, Paul R}, journal = {Front Neuroanat}, volume = {8}, year = {2014}, pages = {46}, abstract = {What explains the superior cognitive abilities of the human brain compared to other, larger brains? Here we investigate the possibility that the human brain has a larger number of neurons than even larger brains by determining the cellular composition of the brain of the African elephant. We find that the African elephant brain, which is about three times larger than the human brain, contains 257 billion (10(9)) neurons, three times more than the average human brain; however, 97.5% of the neurons in the elephant brain (251 billion) are found in the cerebellum. This makes the elephant an outlier in regard to the number of cerebellar neurons compared to other mammals, which might be related to sensorimotor specializations. In contrast, the elephant cerebral cortex, which has twice the mass of the human cerebral cortex, holds only 5.6 billion neurons, about one third of the number of neurons found in the human cerebral cortex. This finding supports the hypothesis that the larger absolute number of neurons in the human cerebral cortex (but not in the whole brain) is correlated with the superior cognitive abilities of humans compared to elephants and other large-brained mammals. }, pubmed = {24971054}, doi = {10.3389/fnana.2014.00046}, pmc = {PMC4053853}, url = {papers/Herculano-Houzel_FrontNeuroanat2014-24971054.pdf}, nlmuniqueid = {101477943} } @article{Kim2020, title = {Extraction of Distinct Neuronal Cell Types from within a Genetically Continuous Population.}, author = {Kim, Euiseok J and Zhang, Zhuzhu and Huang, Ling and Ito-Cole, Tony and Jacobs, Matthew W and Juavinett, Ashley L and Senturk, Gokhan and Hu, Mo and Ku, Manching and Ecker, Joseph R and Callaway, Edward M}, journal = {Neuron}, volume = {107}, number = {2}, year = {2020}, month = {07}, pages = {274-282.e6}, abstract = {Single-cell transcriptomics of neocortical neurons have revealed more than 100 clusters corresponding to putative cell types. For inhibitory and subcortical projection neurons (SCPNs), there is a strong concordance between clusters and anatomical descriptions of cell types. In contrast, cortico-cortical projection neurons (CCPNs) separate into surprisingly few transcriptomic clusters, despite their diverse anatomical projection types. We used projection-dependent single-cell transcriptomic analyses and monosynaptic rabies tracing to compare mouse primary visual cortex CCPNs projecting to different higher visual areas. We find that layer 2/3 CCPNs with different anatomical projections differ systematically in their gene expressions, despite forming only a single genetic cluster. Furthermore, these neurons receive feedback selectively from the same areas to which they project. These findings demonstrate that gene-expression analysis in isolation is insufficient to identify neuron types and have important implications for understanding the functional role of cortical feedback circuits.}, keywords = {cell types; connectivity; cortico-cortical projection neurons; feedback circuits; rabies tracing; single-cell RNA sequencing; visual cortex; Animals; Cerebral Cortex; Feedback; Female; Gene Expression; Gene Knock-In Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neocortex; Nerve Net; Neural Pathways; Neurons; Rabies virus; Transcriptome; Visual Cortex; }, pubmed = {32396852}, pii = {S0896-6273(20)30310-X}, doi = {10.1016/j.neuron.2020.04.018}, pmc = {PMC7381365}, mid = {NIHMS1587972}, url = {papers/Kim_Neuron2020-32396852.pdf}, nlmuniqueid = {8809320} } @article{Goldman1943, title = {POTENTIAL, IMPEDANCE, AND RECTIFICATION IN MEMBRANES.}, author = {Goldman, D E}, journal = {J Gen Physiol}, volume = {27}, number = {1}, year = {1943}, month = {Sep}, pages = {37-60}, abstract = {Impedance and potential measurements have been made on a number of artificial membranes. Impedance changes were determined as functions of current and of the composition of the environmental solutions. It was shown that rectification is present in asymmetrical systems and that it increases with the membrane potential. The behavior in pairs of solutions of the same salt at different concentrations has formed the basis for the studies although a few experiments with different salts at the same concentrations gave results consistent with the conclusions drawn. A theoretical picture has been presented based on the use of the general kinetic equations for ion motion under the influence of diffusion and electrical forces and on a consideration of possible membrane structures. The equations have been solved for two very simple cases; one based on the assumption of microscopic electroneutrality, and the other on the assumption of a constant electric field. The latter was found to give better results than the former in interpreting the data on potentials and rectification, showing agreement, however, of the right order of magnitude only. Although the indications are that a careful treatment of boundary conditions may result in better agreement with experiment, no attempt has been made to carry this through since the data now available are not sufficiently complete or reproducible. Applications of the second theoretical case to the squid giant axon have been made showing qualitative agreement with the rectification properties and very good agreement with the membrane potential data.}, pubmed = {19873371}, doi = {10.1085/jgp.27.1.37}, url = {papers/Goldman_JGenPhysiol1943-19873371.pdf}, nlmuniqueid = {2985110R} } @article{Pickard1976, title = {Generalizations of the Goldman-Hodgkin-Katz equation}, journal = {Mathematical Biosciences}, volume = {30}, number = {1}, pages = {99-111}, year = {1976}, issn = {0025-5564}, doi = {10.1016/0025-5564(76)90018-3}, url = {papers/Pickard_MathBiosci1976.pdf}, author = {Pickard, William F}, abstract = {Closed-form expressions for the potential across a membrane are derived for a variety of cases. Among these are: (i) exact expressions for no electrogenic pump and (a) mixed uni- and divalent ions, (b) mixed uni-, di-, and tervalent ions, and (c) mixed univalent ions and a leak proportional to the membrane voltage; and (ii) approximate expressions for mixed univalent ions and a hyperpolarizing or weakly depolarizing electrogenic pump.} } @article{Spangler1972, title = {Expansion of the constant field equation to include both divalent and monovalent ions.}, author = {Spangler, S G}, journal = {Ala J Med Sci}, volume = {9}, number = {2}, year = {1972}, month = {Apr}, pages = {218-23}, keywords = {Chemical Phenomena; Chemistry, Physical; Ions; Mathematics; Membranes; Permeability; }, pubmed = {5045041}, url = {}, nlmuniqueid = {0376521} } @article{Springel2005, title = {Simulations of the formation, evolution and clustering of galaxies and quasars.}, author = {Springel, Volker and White, Simon D M and Jenkins, Adrian and Frenk, Carlos S and Yoshida, Naoki and Gao, Liang and Navarro, Julio and Thacker, Robert and Croton, Darren and Helly, John and Peacock, John A and Cole, Shaun and Thomas, Peter and Couchman, Hugh and Evrard, August and Colberg, Jörg and Pearce, Frazer}, journal = {Nature}, volume = {435}, number = {7042}, year = {2005}, month = {Jun}, pages = {629-36}, abstract = {The cold dark matter model has become the leading theoretical picture for the formation of structure in the Universe. This model, together with the theory of cosmic inflation, makes a clear prediction for the initial conditions for structure formation and predicts that structures grow hierarchically through gravitational instability. Testing this model requires that the precise measurements delivered by galaxy surveys can be compared to robust and equally precise theoretical calculations. Here we present a simulation of the growth of dark matter structure using 2,160(3) particles, following them from redshift z = 127 to the present in a cube-shaped region 2.230 billion lightyears on a side. In postprocessing, we also follow the formation and evolution of the galaxies and quasars. We show that baryon-induced features in the initial conditions of the Universe are reflected in distorted form in the low-redshift galaxy distribution, an effect that can be used to constrain the nature of dark energy with future generations of observational surveys of galaxies.}, pubmed = {15931216}, pii = {nature03597}, doi = {10.1038/nature03597}, url = {papers/Springel_Nature2005-15931216.pdf}, nlmuniqueid = {0410462} }